WorldWideScience

Sample records for deficiency diseases

  1. Sleep Deficiency and Deprivation Leading to Cardiovascular Disease

    Directory of Open Access Journals (Sweden)

    Michelle Kohansieh

    2015-01-01

    Full Text Available Sleep plays a vital role in an individual’s mental, emotional, and physiological well-being. Not only does sleep deficiency lead to neurological and psychological disorders, but also the literature has explored the adverse effects of sleep deficiency on the cardiovascular system. Decreased quantity and quality of sleep have been linked to cardiovascular disease (CVD risk factors, such as hypertension, obesity, diabetes, and dyslipidemia. We explore the literature correlating primary sleep deficiency and deprivation as a cause for cardiovascular disease and cite endothelial dysfunction as a common underlying mechanism.

  2. Iron deficiency anemia in patients with inflammatory bowel disease

    Directory of Open Access Journals (Sweden)

    Goldberg ND

    2013-06-01

    Full Text Available Neil D Goldberg Emeritus Chief of Gastroenterology, University of Maryland St. Joseph Medical Center, Towson, MD, USA Abstract: Iron deficiency anemia is the most common form of anemia worldwide, caused by poor iron intake, chronic blood loss, or impaired absorption. Patients with inflammatory bowel disease (IBD are increasingly likely to have iron deficiency anemia, with an estimated prevalence of 36%–76%. Detection of iron deficiency is problematic as outward signs and symptoms are not always present. Iron deficiency can have a significant impact on a patient's quality of life, necessitating prompt management and treatment. Effective treatment includes identifying and treating the underlying cause and initiating iron replacement therapy with either oral or intravenous iron. Numerous formulations for oral iron are available, with ferrous fumarate, sulfate, and gluconate being the most commonly prescribed. Available intravenous formulations include iron dextran, iron sucrose, ferric gluconate, and ferumoxytol. Low-molecular weight iron dextran and iron sucrose have been shown to be safe, efficacious, and effective in a host of gastrointestinal disorders. Ferumoxytol is the newest US Food and Drug Administration-approved intravenous iron therapy, indicated for iron deficiency anemia in adults with chronic kidney disease. Ferumoxytol is also being investigated in Phase 3 studies for the treatment of iron deficiency anemia in patients without chronic kidney disease, including subgroups with IBD. A review of the efficacy and safety of iron replacement in IBD, therapeutic considerations, and recommendations for the practicing gastroenterologist are presented. Keywords: anemia, inflammatory bowel disease, intravenous iron, iron deficiency, oral iron, therapy

  3. Iron Deficiency Anemia: A Common and Curable Disease

    Science.gov (United States)

    Miller, Jeffery L.

    2013-01-01

    Iron deficiency anemia arises when the balance of iron intake, iron stores, and the body's loss of iron are insufficient to fully support production of erythrocytes. Iron deficiency anemia rarely causes death, but the impact on human health is significant. In the developed world, this disease is easily identified and treated, but frequently overlooked by physicians. In contrast, it is a health problem that affects major portions of the population in underdeveloped countries. Overall, the prevention and successful treatment for iron deficiency anemia remains woefully insufficient worldwide, especially among underprivileged women and children. Here, clinical and laboratory features of the disease are discussed, and then focus is placed on relevant economic, environmental, infectious, and genetic factors that converge among global populations. PMID:23613366

  4. Iron-deficiency anemia as a subclinical celiac disease presentation in an Argentinian population.

    Science.gov (United States)

    Lasa, J S; Olivera, P; Soifer, L; Moore, R

    There is a wide heterogeneity in the reports of celiac disease prevalence in iron-deficiency anemia patients. To determine the prevalence of celiac disease in patients with iron-deficiency anemia. Adult patients with a diagnosis of iron-deficiency anemia were enrolled for upper endoscopy with duodenal biopsies. Healthy volunteers that underwent upper endoscopy were enrolled as controls. A total of 135 patients with iron-deficiency anemia and 133 controls were enrolled. Celiac disease prevalence was higher in the iron-deficiency anemia group [11.11 vs. 1.51%, OR: 8.18 (1.83-36.55), P=.001). Of the celiac disease patients in the iron-deficiency anemia group, 73.3% had at least one endoscopic sign suggesting villous atrophy, whereas 100% of the celiac disease patients in the control group presented with at least one endoscopic sign. Patients with iron-deficiency anemia have an increased risk for celiac disease. Up to 25% of these patients may not present any endoscopic sign suggesting villous atrophy. Copyright © 2017 Asociación Mexicana de Gastroenterología. Publicado por Masson Doyma México S.A. All rights reserved.

  5. Vitamin D deficiency in patients with either rheumatic diseases or inflammatory bowel diseases on biologic therapy.

    Science.gov (United States)

    Bruzzese, Vincenzo; Zullo, Angelo; Picchianti Diamanti, Andrea; Ridola, Lorenzo; Lorenzetti, Roberto; Marrese, Cinzia; Scolieri, Palma; De Francesco, Vincenzo; Hassan, Cesare; Migliore, Alberto; Laganà, Bruno

    2016-09-01

    Vitamin D deficiency has been reported in patients with chronic inflammatory conditions, such as rheumatic and inflammatory bowel diseases (IBD). We evaluated the role of biologic therapy on vitamin D, calcium and parathormone (PTH) levels. This cross-sectional study enrolled consecutive patients with either rheumatic diseases or IBD who underwent an ambulatory visit. Patients receiving vitamin D/calcium supplementation were excluded. Vitamin D deficiency or insufficiency was diagnosed when values were rheumatic disease (M/F 37/99; mean age 60.7 ± 12.9 years) and 64 with IBD (M/F 41/23; Mean age 49.6 ± 13.1 years) were enrolled. Vitamin D deficiency/insufficiency was detected in as many as 63.5 % patients, being 61.8 and 67.2 % in patients with either rheumatic diseases or IBD, respectively. The prevalence of vitamin D deficiency/insufficiency was higher in those receiving biologics than other therapies (78.3 vs 43.2 %; p rheumatic diseases (78.7 vs 41 %; p rheumatic diseases or IBD receiving a biologic therapy.

  6. GATA2 Deficiency and Epstein–Barr Virus Disease

    Directory of Open Access Journals (Sweden)

    Jeffrey I. Cohen

    2017-12-01

    Full Text Available GATA2 is a transcription factor that binds to the promoter of hematopoietic genes. Mutations in one copy of the gene are associated with haploinsufficiency and reduced levels of protein. This results in reduced numbers of several cell types important for immune surveillance including dendritic cells, monocytes, CD4, and NK cells, as well as impaired NK cell function. Recently, GATA2 has been associated with several different presentations of severe Epstein–Barr virus (EBV disease including primary infection requiring repeated hospitalizations, chronic active EBV disease, EBV-associated hydroa vacciniforme with hemophagocytosis, and EBV-positive smooth muscle tumors. EBV was found predominantly in B cells in each of the cases in which it was studied, unlike most cases of chronic active EBV disease in which the virus is usually present in T or NK cells. The variety of EBV-associated diseases seen in patients with GATA2 deficiency suggest that additional forms of severe EBV disease may be found in patients with GATA2 deficiency in the future.

  7. GATA2 Deficiency and Epstein-Barr Virus Disease.

    Science.gov (United States)

    Cohen, Jeffrey I

    2017-01-01

    GATA2 is a transcription factor that binds to the promoter of hematopoietic genes. Mutations in one copy of the gene are associated with haploinsufficiency and reduced levels of protein. This results in reduced numbers of several cell types important for immune surveillance including dendritic cells, monocytes, CD4, and NK cells, as well as impaired NK cell function. Recently, GATA2 has been associated with several different presentations of severe Epstein-Barr virus (EBV) disease including primary infection requiring repeated hospitalizations, chronic active EBV disease, EBV-associated hydroa vacciniforme with hemophagocytosis, and EBV-positive smooth muscle tumors. EBV was found predominantly in B cells in each of the cases in which it was studied, unlike most cases of chronic active EBV disease in which the virus is usually present in T or NK cells. The variety of EBV-associated diseases seen in patients with GATA2 deficiency suggest that additional forms of severe EBV disease may be found in patients with GATA2 deficiency in the future.

  8. Management of Iron-Deficiency Anemia in Inflammatory Bowel Disease

    Science.gov (United States)

    Nielsen, Ole Haagen; Ainsworth, Mark; Coskun, Mehmet; Weiss, Günter

    2015-01-01

    Abstract Anemia is the most frequent complication of inflammatory bowel disease (IBD), but anemia, mostly due to iron deficiency, has long been neglected in these patients. The aim was to briefly present the pathophysiology, followed by a balanced overview of the different forms of iron replacement available, and subsequently, to perform a systematic review of studies performed in the last decade on the treatment of iron-deficiency anemia in IBD. Given that intravenous therapies have been introduced in the last decade, a systematic review performed in PubMed, EMBASE, the Cochrane Library, and the websites of WHO, FDA, and EMA covered prospective trials investigating the management of iron-deficiency anemia in IBD published since 2004. A total of 632 articles were reviewed, and 13 articles (2906 patients) with unique content were included. In general, oral supplementation in iron-deficiency anemia should be administered with a target to restore/replenish the iron stores and the hemoglobin level in a suitable way. However, in patients with IBD flares and inadequate responses to or side effects with oral preparations, intravenous iron supplementation is the therapy of choice. Neither oral nor intravenous therapy seems to exacerbate the clinical course of IBD, and intravenous iron therapy can be administered even in active disease stages and concomitantly with biologics. In conclusion, because many physicians are in doubt as to how to manage anemia and iron deficiency in IBD, there is a clear need for the implementation of evidence-based recommendations on this matter. Based on the data presented, oral iron therapy should be preferred for patients with quiescent disease stages and trivial iron deficiency anemia unless such patients are intolerant or have an inadequate response, whereas intravenous iron supplementation may be of advantage in patients with aggravated anemia or flares of IBD because inflammation hampers intestinal absorption of iron. PMID:26061331

  9. Does Vitamin C Deficiency Promote Fatty Liver Disease Development?

    Directory of Open Access Journals (Sweden)

    David Højland Ipsen

    2014-12-01

    Full Text Available Obesity and the subsequent reprogramming of the white adipose tissue are linked to human disease-complexes including metabolic syndrome and concurrent non-alcoholic fatty liver disease (NAFLD and non-alcoholic steatohepatitis (NASH. The dietary imposed dyslipidemia promotes redox imbalance by the generation of excess levels of reactive oxygen species and induces adipocyte dysfunction and reprogramming, leading to a low grade systemic inflammation and ectopic lipid deposition, e.g., in the liver, hereby promoting a vicious circle in which dietary factors initiate a metabolic change that further exacerbates the negative consequences of an adverse life-style. Large epidemiological studies and findings from controlled in vivo animal studies have provided evidence supporting an association between poor vitamin C (VitC status and propagation of life-style associated diseases. In addition, overweight per se has been shown to result in reduced plasma VitC, and the distribution of body fat in obesity has been shown to have an inverse relationship with VitC plasma levels. Recently, a number of epidemiological studies have indicated a VitC intake below the recommended daily allowance (RDA in NAFLD-patients, suggesting an association between dietary habits, disease and VitC deficiency. In the general population, VitC deficiency (defined as a plasma concentration below 23 μM affects around 10% of adults, however, this prevalence is increased by an adverse life-style, deficiency potentially playing a broader role in disease progression in specific subgroups. This review discusses the currently available data from human surveys and experimental models in search of a putative role of VitC deficiency in the development of NAFLD and NASH.

  10. Vitamin D deficiency and heart disease

    NARCIS (Netherlands)

    Pilz, Stefan; Tomaschitz, Andreas; Drechsler, Christiane; de Boer, Rudolf A.

    Vitamin D deficiency is present in the vast majority of patients with chronic kidney disease (CKD), and correcting a poor vitamin D status is recommended as a treatment of CKD-mineral and bone disorders. In this review, we summarize the molecular and clinical data on the role of vitamin D status for

  11. Bone marrow transplantation for correction of enzyme deficiency disease

    International Nuclear Information System (INIS)

    Hong, C.; Sutherland, D.E.R.; Matas, A.J.; Najarian, J.S.

    1979-01-01

    Mutant acatalasemic mice provide a prototype of congenital enzyme deficiency disease. Normal blood catalase levels were achieved permanently in congenitally acatalasemic mice by transplantation of bone marrow cells from congeneic normal catalasemic mice using relatively small numbers of cells following whole body irradiation. The increase in blood catalase activity was physiologically effective as demonstrated by the protection of the previously acatalasemic mice against the otherwise lethal effects of hydrogen peroxide injections. Bone marrow transplantation has the potential to provide a continuous source of some enzymes and may be applicable as treatment for certain congenital enzyme deficiency diseases

  12. Immune Deficiency Disease' of Undetermined Aetiology in Infancy

    African Journals Online (AJOL)

    1974-04-06

    Apr 6, 1974 ... J., 48, 687 (1974). Immune deficiency diseases in infancy are best known as ... tion at the age of 10 months confirmed the mental retarda- tion, and on further ... Examination of other organ systems was non-contributory. Triple .... linked recessive transmitted disease, and has not been re- ported in females.

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

    Directory of Open Access Journals (Sweden)

    Takashi Himoto

    2018-01-01

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

  14. Gene targeted therapeutics for liver disease in alpha-1 antitrypsin deficiency.

    LENUS (Irish Health Repository)

    McLean, Caitriona

    2009-01-01

    Alpha-1 antitrypsin (A1AT) is a 52 kDa serine protease inhibitor that is synthesized in and secreted from the liver. Although it is present in all tissues in the body the present consensus is that its main role is to inhibit neutrophil elastase in the lung. A1AT deficiency occurs due to mutations of the A1AT gene that reduce serum A1AT levels to <35% of normal. The most clinically significant form of A1AT deficiency is caused by the Z mutation (Glu342Lys). ZA1AT polymerizes in the endoplasmic reticulum of liver cells and the resulting accumulation of the mutant protein can lead to liver disease, while the reduction in circulating A1AT can result in lung disease including early onset emphysema. There is currently no available treatment for the liver disease other than transplantation and therapies for the lung manifestations of the disease remain limited. Gene therapy is an evolving field which may be of use as a treatment for A1AT deficiency. As the liver disease associated with A1AT deficiency may represent a gain of function possible gene therapies for this condition include the use of ribozymes, peptide nucleic acids (PNAs) and RNA interference (RNAi), which by decreasing the amount of aberrant protein in cells may impact on the pathogenesis of the condition.

  15. A rare form of Gaucher disease resulting from saposin C deficiency.

    Science.gov (United States)

    Kang, Lulu; Zhan, Xia; Ye, Jun; Han, Lianshu; Qiu, Wenjuan; Gu, Xuefan; Zhang, Huiwen

    2018-02-01

    Gaucher disease is mainly caused by the deficiency of lysosomal acid β-glucosidase. Gaucher disease caused by the deficiency of saposin C is rare. Here we report a patient mainly presenting with hepatosplenomegaly, thrombocytopenia and anemia. EEG examination revealed increased theta waves. Gaucher cells identified in his bone marrow and the highly elevated plasma chitotriosidase activity and glucosylsphingosine supported a diagnosis of Gaucher disease. However, the leukocyte β-glucosidase activity was in a normal range. Sanger sequencing revealed a novel maternal exonic mutation c.1133C>G (p.Pro378Arg) in exon 10 of the PSAP gene, which codes the Sap C domain of PSAP protein. To search for other underlying mutations in this patient, whole genome sequencing was applied and revealed a deletion involving exon 2 to 7 of PSAP gene. The deletion appears as a de novo event on paternal chromosome. We concluded that biallelic mutations of PSAP gene were the cause of this patient's Gaucher disease. Our finding expands the mutation spectrum of Gaucher disease with saposin C deficiency. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Celiac Disease in Children with Moderate-to-Severe Iron-deficiency Anemia.

    Science.gov (United States)

    Narang, Manish; Natarajan, Ravikumar; Shah, Dheeraj; Puri, Amarender Singh; Manchanda, Vikas; Kotru, Mrinalini

    2018-01-15

    To evaluate the proportion of children with moderate to severe iron-deficiency anemia who have associated celiac disease. This cross-sectional analytical study was conducted among children aged 1 to 12 years of age with moderate-to-severe iron deficiency anemia and control children without anemia. Serum IgA-tissue trans-glutaminase levels were assessed in both cases and controls. All children with positive celiac serology underwent upper gastrointestinal endoscopy and duodenal biopsy; biopsy finding of Marsh grade 3 was considered positive for celiac disease. There were 152 anemic children and 152 controls with mean (SD) hemoglobinof 7.7 (1.8) and 12.2 (0.74) g/dL, respectively. 16 (10.5%) cases and 3 (2%) control patients had positive serology for celiac disease [OR (95% CI) 5.33 (1.52-18.67), P=0.007]. Six (3.9%) children with iron-deficiency anemia and none of the controls had biopsy features diagnostic of celiac disease. In the Northern Indian tertiary-care hospital outpatient setting, Celiac disease was associated with 4% of children presenting with moderate-to-severe anemia.

  17. 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.

  18. Diagnosis of Iron-Deficiency Anemia in Chronic Kidney Disease.

    Science.gov (United States)

    Bahrainwala, Jehan; Berns, Jeffrey S

    2016-03-01

    Anemia is a common and clinically important consequence of chronic kidney disease (CKD). It is most commonly a result of decreased erythropoietin production by the kidneys and/or iron deficiency. Deciding on the appropriate treatment for anemia associated with CKD with iron replacement and erythropoietic-stimulating agents requires an ability to accurately diagnose iron-deficiency anemia. However, the diagnosis of iron-deficiency anemia in CKD patients is complicated by the relatively poor predictive ability of easily obtained routine serum iron indices (eg, ferritin and transferrin saturation) and more invasive gold standard measures of iron deficiency (eg, bone marrow iron stores) or erythropoietic response to supplemental iron. In this review, we discuss the diagnostic utility of currently used serum iron indices and emerging alternative markers of iron stores. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Sociodemographic and cultural determinants of sleep deficiency: implications for cardiometabolic disease risk.

    Science.gov (United States)

    Knutson, Kristen L

    2013-02-01

    Sleep is a biological imperative associated with cardiometabolic disease risk. As such, a thorough discussion of the sociocultural and demographic determinants of sleep is warranted, if not overdue. This paper begins with a brief review of the laboratory and epidemiologic evidence linking sleep deficiency, which includes insufficient sleep and poor sleep quality, with increased risk of chronic cardiometabolic diseases such as obesity, diabetes and hypertension. Identification of the determinants of sleep deficiency is the critical next step to understanding the role sleep plays in human variation in health and disease. Therefore, the majority of this paper describes the different biopsychosocial determinants of sleep, including age, gender, psychosocial factors (depression, stress and loneliness), socioeconomic position and race/ethnicity. In addition, because sleep duration is partly determined by behavior, it will be shaped by cultural values, beliefs and practices. Therefore, possible cultural differences that may impact sleep are discussed. If certain cultural, ethnic or social groups are more likely to experience sleep deficiency, then these differences in sleep could increase their risk of cardiometabolic diseases. Furthermore, if the mechanisms underlying the increased risk of sleep deficiency in certain populations can be identified, interventions could be developed to target these mechanisms, reduce sleep differences and potentially reduce cardiometabolic disease risk. Copyright © 2012 Elsevier Ltd. All rights reserved.

  20. Gene targeted therapeutics for liver disease in alpha-1 antitrypsin deficiency

    Directory of Open Access Journals (Sweden)

    Caitriona McLean

    2009-01-01

    Full Text Available Caitriona McLean*, Catherine M Greene*, Noel G McElvaneyRespiratory Research Division, Dept. Medicine, Royal College of Surgeons in Ireland, Education and Research Centre, Beaumont Hospital, Dublin 9, Ireland; *Each of these authors contributed equally to this workAbstract: Alpha-1 antitrypsin (A1AT is a 52 kDa serine protease inhibitor that is synthesized in and secreted from the liver. Although it is present in all tissues in the body the present consensus is that its main role is to inhibit neutrophil elastase in the lung. A1AT deficiency occurs due to mutations of the A1AT gene that reduce serum A1AT levels to <35% of normal. The most clinically significant form of A1AT deficiency is caused by the Z mutation (Glu342Lys. ZA1AT polymerizes in the endoplasmic reticulum of liver cells and the resulting accumulation of the mutant protein can lead to liver disease, while the reduction in circulating A1AT can result in lung disease including early onset emphysema. There is currently no available treatment for the liver disease other than transplantation and therapies for the lung manifestations of the disease remain limited. Gene therapy is an evolving field which may be of use as a treatment for A1AT deficiency. As the liver disease associated with A1AT deficiency may represent a gain of function possible gene therapies for this condition include the use of ribozymes, peptide nucleic acids (PNAs and RNA interference (RNAi, which by decreasing the amount of aberrant protein in cells may impact on the pathogenesis of the condition.Keywords: alpha-1 antitrypsin deficiency, siRNA, peptide nucleic acid, ribozymes

  1. Management of Iron-Deficiency Anemia in Inflammatory Bowel Disease

    DEFF Research Database (Denmark)

    Nielsen, Ole Haagen; Ainsworth, Mark; Coskun, Mehmet

    2015-01-01

    Anemia is the most frequent complication of inflammatory bowel disease (IBD), but anemia, mostly due to iron deficiency, has long been neglected in these patients. The aim was to briefly present the pathophysiology, followed by a balanced overview of the different forms of iron replacement...... available, and subsequently, to perform a systematic review of studies performed in the last decade on the treatment of iron-deficiency anemia in IBD. Given that intravenous therapies have been introduced in the last decade, a systematic review performed in PubMed, EMBASE, the Cochrane Library......, and the websites of WHO, FDA, and EMA covered prospective trials investigating the management of iron-deficiency anemia in IBD published since 2004. A total of 632 articles were reviewed, and 13 articles (2906 patients) with unique content were included. In general, oral supplementation in iron-deficiency anemia...

  2. Iron deficiency anemia in inflammatory bowel disease

    Science.gov (United States)

    Kaitha, Sindhu; Bashir, Muhammad; Ali, Tauseef

    2015-01-01

    Anemia is a common extraintestinal manifestation of inflammatory bowel disease (IBD) and is frequently overlooked as a complication. Patients with IBD are commonly found to have iron deficiency anemia (IDA) secondary to chronic blood loss, and impaired iron absorption due to tissue inflammation. Patients with iron deficiency may not always manifest with signs and symptoms; so, hemoglobin levels in patients with IBD must be regularly monitored for earlier detection of anemia. IDA in IBD is associated with poor quality of life, necessitating prompt diagnosis and appropriate treatment. IDA is often associated with inflammation in patients with IBD. Thus, commonly used laboratory parameters are inadequate to diagnose IDA, and newer iron indices, such as reticulocyte hemoglobin content or percentage of hypochromic red cells or zinc protoporphyrin, are required to differentiate IDA from anemia of chronic disease. Oral iron preparations are available and are used in patients with mild disease activity. These preparations are inexpensive and convenient, but can produce gastrointestinal side effects, such as abdominal pain and diarrhea, that limit their use and patient compliance. These preparations are partly absorbed due to inflammation. Non-absorbed iron can be toxic and worsen IBD disease activity. Although cost-effective intravenous iron formulations are widely available and have improved safety profiles, physicians are reluctant to use them. We present a review of the pathophysiologic mechanisms of IDA in IBD, improved diagnostic and therapeutic strategies, efficacy, and safety of iron replacement in IBD. PMID:26301120

  3. Glucose-6-phosphate dehydrogenase deficiency and Alzheimer's disease: Partners in crime? The hypothesis.

    Science.gov (United States)

    Ulusu, N Nuray

    2015-08-01

    Alzheimer's disease is a multifaceted brain disorder which involves various coupled irreversible, progressive biochemical reactions that significantly reduce quality of life as well as the actual life expectancy. Aging, genetic predispositions, head trauma, diabetes, cardiovascular disease, deficiencies in insulin signaling, dysfunction of mitochondria-associated membranes, cerebrovascular changes, high cholesterol level, increased oxidative stress and free radical formation, DNA damage, disturbed energy metabolism, and synaptic dysfunction, high blood pressure, obesity, dietary habits, exercise, social engagement, and mental stress are noted among the risk factors of this disease. In this hypothesis review I would like to draw the attention on glucose-6-phosphate dehydrogenase deficiency and its relationship with Alzheimer's disease. This enzymopathy is the most common human congenital defect of metabolism and defined by decrease in NADPH+H(+) and reduced form of glutathione concentration and that might in turn, amplify oxidative stress due to essentiality of the enzyme. This most common enzymopathy may manifest itself in severe forms, however most of the individuals with this deficiency are not essentially symptomatic. To understand the sporadic Alzheimer's disease, the writer of this paper thinks that, looking into a crystal ball might not yield much of a benefit but glucose-6-phosphate dehydrogenase deficiency could effortlessly give some clues. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. On the Possible Link between Vitamin D Deficiency and Cardiovascular Disease

    Science.gov (United States)

    ... the Possible Link Between Vitamin D Deficiency and Cardiovascular Disease Should We D-Lighten Our Lives? Pelle G. ... Individuals with heart failure, hypertension, stroke, and other cardiovascular diseases (CVD) tend to have lower vitamin D levels ...

  5. Evaluation of dose response effects related to nutritional diseases (mineral deficiencies) in ruminants

    International Nuclear Information System (INIS)

    Goksoy, K.; Gucus, A.I.; Morcol, T.

    1986-01-01

    Nutritional diseases (mineral deficiencies) of farm animals are one of the limiting factors in animal production in Turkey. Present knowledge of mineral deficiencies of farm animals is derived from the study of severe deficiency conditions. Examples in sheep are deficiencies of copper in the central area of the Black Sea region and of selenium in the interior of Anatolia. Phosphorus deficiency is becoming the most serious problem in cattle. Outbreaks of wool shedding in sheep in central Anatolia are also becoming more severe. It is also likely that moderate (borderline) mineral deficiencies exist on a large scale. A general overview of trace mineral deficiencies and recent studies carried out to diagnose and correct them with the aid of biochemical and radioisotopic parameters is presented and discussed. (author)

  6. Is PiSS Alpha-1 Antitrypsin Deficiency Associated with Disease?

    Science.gov (United States)

    McGee, Dawn; Schwarz, Laura; McClure, Rebecca; Peterka, Lauren; Rouhani, Farshid; Brantly, Mark; Strange, Charlie

    2010-01-01

    Background. Alpha-1 antitrypsin deficiency (AAT) is an inherited condition that predisposes to lung and/or liver disease. Objective. The current study examined the clinical features of the PiSS genotype. Methods. Nineteen study participants (PiSS) and 29 matched control participants (PiMM) were telephone interviewed using a standardized questionnaire. Demographic features, cigarette smoking, vocation, medication history, and clinical diagnoses were compared. Statistical analysis was performed. Finally, a comprehensive literature review was performed by two investigators. Results. 12/19 (63.2%) study participants reported the presence of lung and/or liver disease compared to 12/29 (41.4%) control participants. There trended toward having a higher frequency of medication allergies in the study population (42.11% versus 20.69%). Conclusions. The PiSS genotype was associated with a similar incidence of obstructive lung disease to controls. Selective bias intrinsic in testing for AAT deficiency and the rarity of the PiSS genotype will make future study of this association dependent on population-based tests.

  7. Management of Iron-Deficiency Anemia in Inflammatory Bowel Disease: A Systematic Review.

    Science.gov (United States)

    Nielsen, Ole Haagen; Ainsworth, Mark; Coskun, Mehmet; Weiss, Günter

    2015-06-01

    Anemia is the most frequent complication of inflammatory bowel disease (IBD), but anemia, mostly due to iron deficiency, has long been neglected in these patients. The aim was to briefly present the pathophysiology, followed by a balanced overview of the different forms of iron replacement available, and subsequently, to perform a systematic review of studies performed in the last decade on the treatment of iron-deficiency anemia in IBD. Given that intravenous therapies have been introduced in the last decade, a systematic review performed in PubMed, EMBASE, the Cochrane Library, and the websites of WHO, FDA, and EMA covered prospective trials investigating the management of iron-deficiency anemia in IBD published since 2004. A total of 632 articles were reviewed, and 13 articles (2906 patients) with unique content were included. In general, oral supplementation in iron-deficiency anemia should be administered with a target to restore/replenish the iron stores and the hemoglobin level in a suitable way. However, in patients with IBD flares and inadequate responses to or side effects with oral preparations, intravenous iron supplementation is the therapy of choice. Neither oral nor intravenous therapy seems to exacerbate the clinical course of IBD, and intravenous iron therapy can be administered even in active disease stages and concomitantly with biologics. In conclusion, because many physicians are in doubt as to how to manage anemia and iron deficiency in IBD, there is a clear need for the implementation of evidence-based recommendations on this matter. Based on the data presented, oral iron therapy should be preferred for patients with quiescent disease stages and trivial iron deficiency anemia unless such patients are intolerant or have an inadequate response, whereas intravenous iron supplementation may be of advantage in patients with aggravated anemia or flares of IBD because inflammation hampers intestinal absorption of iron.

  8. Diagnosis of alpha-1-antitrypsin deficiency by DNA analysis of children with liver disease

    Directory of Open Access Journals (Sweden)

    De TOMMASO Adriana Maria Alves

    2001-01-01

    Full Text Available Background - Alpha-1-antitrypsin deficiency is a genetic disorder which is transmitted in a co-dominant, autosomal form. Alpha-1-antitrypsin deficiency affects mainly the lungs and the liver leading, in the latter case, to neonatal cholestasis, chronic hepatitis or cirrhosis. A precise diagnosis of Alpha-1-antitrypsin deficiency may be obtained by biochemical or molecular analysis. Objective - The purpose of this study was to use DNA analysis to examine the presence of an alpha-1-antitrypsin deficiency in 12 children suspected of having this deficiency and who showed laboratory and clinical characteristics of the disease. Patients and Methods - Twelve patients, aged 3 months to 19 years, who had serum alpha-1-antitrypsin levels lower than normal and/or had hepatic disease of undefined etiology were studied. The mutant alleles S and Z of the alpha-1-antitrypsin gene were investigated in the 12 children. Alpha-1-antitrypsin gene organization was analyzed by amplification of genoma through the polymerase chain reaction and digestion with the restriction enzymes Xmnl (S allele and Taq 1 (Z allele. Results - Seven of the 12 patients had chronic liver disease of undefined etiology and the other five patients had low serum levels of alpha-1-antitrypsin as well as a diagnosis of neonatal cholestasis and/or chronic liver disease of undefined etiology. Five of the 12 patients were homozygous for the Z allele (ZZ and two had the S allele with another allele (*S different from Z. Conclusion - These results show that alpha-1-antitrypsin deficiency is relatively frequent in children with chronic hepatic disease of undefined etiology and/or low alpha-1-antitrypsin levels (41.6%. A correct diagnosis is important for effective clinical follow-up and for genetic counseling.

  9. Iron Deficiency Anemia: Focus on Infectious Diseases in Lesser Developed Countries

    Science.gov (United States)

    Shaw, Julia G.; Friedman, Jennifer F.

    2011-01-01

    Iron deficiency anemia is thought to affect the health of more than one billion people worldwide, with the greatest burden of disease experienced in lesser developed countries, particularly women of reproductive age and children. This greater disease burden is due to both nutritional and infectious etiologies. Individuals in lesser developed countries have diets that are much lower in iron, less access to multivitamins for young children and pregnant women, and increased rates of fertility which increase demands for iron through the life course. Infectious diseases, particularly parasitic diseases, also lead to both extracorporeal iron loss and anemia of inflammation, which decreases bioavailability of iron to host tissues. This paper will address the unique etiologies and consequences of both iron deficiency anemia and the alterations in iron absorption and distribution seen in the context of anemia of inflammation. Implications for diagnosis and treatment in this unique context will also be discussed. PMID:21738863

  10. Iron Deficiency Anemia: Focus on Infectious Diseases in Lesser Developed Countries

    Directory of Open Access Journals (Sweden)

    Julia G. Shaw

    2011-01-01

    Full Text Available Iron deficiency anemia is thought to affect the health of more than one billion people worldwide, with the greatest burden of disease experienced in lesser developed countries, particularly women of reproductive age and children. This greater disease burden is due to both nutritional and infectious etiologies. Individuals in lesser developed countries have diets that are much lower in iron, less access to multivitamins for young children and pregnant women, and increased rates of fertility which increase demands for iron through the life course. Infectious diseases, particularly parasitic diseases, also lead to both extracorporeal iron loss and anemia of inflammation, which decreases bioavailability of iron to host tissues. This paper will address the unique etiologies and consequences of both iron deficiency anemia and the alterations in iron absorption and distribution seen in the context of anemia of inflammation. Implications for diagnosis and treatment in this unique context will also be discussed.

  11. Subacute copper-deficiency myelopathy in a patient with occult celiac disease.

    Science.gov (United States)

    Cavallieri, Francesco; Fini, Nicola; Contardi, Sara; Fiorini, Massimo; Corradini, Elena; Valzania, Franco

    2017-07-01

    Acquired copper deficiency represents a rare cause of progressive myelopathy presenting with sensory ataxia and spastic gait. The time interval from neurological symptoms onset to diagnosis of myelopathy ranges from 2 months to several years in almost all cases, mimicking the clinical course of subacute combined degeneration due to vitamin B12 deficiency. A 60-year-old man, without any gastrointestinal symptoms, developed over the course of one week rapidly progressive gait imbalance, tingling and numbness in his feet and ascending lower limb weakness. Spine magnetic resonance imaging revealed hyperintensity involving cervical and dorsal posterior columns of spinal cord. Blood analysis revealed undetectable serum copper levels, low serum ceruloplasmin and positive serum Immunoglobulin A anti-tissue transglutaminase. Upper gastrointestinal endoscopy was performed revealing duodenal villous atrophy consistent with a malabsorption pattern. A gluten-free diet in association with intravenous then oral copper supplementation prompted sustained normalization of serum copper levels and progressive clinical improvement. We report a rare case of myelopathy induced by copper deficiency secondary to undiagnosed celiac disease, peculiarly presenting with a subacute onset. This case expands the neurological presentation and clinical course of myelopathy due to acquired copper deficiency. We suggest investigation of copper deficiency in patients presenting with subacute or even acute sensory ataxia and spastic gait. Detection of hypocupremia in patients without a previous history of gastric surgery should lead to diagnostic testing for celiac disease even in the absence of any obvious gastrointestinal symptoms.

  12. Blood pressure, risk of ischemic cerebrovascular and ischemic heart disease, and longevity in alpha(1)-antitrypsin deficiency

    DEFF Research Database (Denmark)

    Dahl, Morten; Tybjaerg-Hansen, Anne; Sillesen, Henrik

    2003-01-01

    Because elastase in alpha(1)-antitrypsin deficiency may attack elastin in the arterial wall, we tested whether alpha(1)-antitrypsin deficiency is associated with reduced blood pressure, risk of ischemic cerebrovascular (ICVD) and ischemic heart disease (IHD), and longevity.......Because elastase in alpha(1)-antitrypsin deficiency may attack elastin in the arterial wall, we tested whether alpha(1)-antitrypsin deficiency is associated with reduced blood pressure, risk of ischemic cerebrovascular (ICVD) and ischemic heart disease (IHD), and longevity....

  13. Estimating the burden of disease attributable to iron deficiency ...

    African Journals Online (AJOL)

    Objectives. To estimate the extent of iron deficiency anaemia (IDA) among children aged 0 - 4 years and pregnant women aged 15 - 49 years, and the burden of disease attributed to IDA in South Africa in 2000. Design. The comparative risk assessment (CRA) methodology of the World Health Organization (WHO) was ...

  14. Is PiSS Alpha-1 Antitrypsin Deficiency Associated with Disease?

    Directory of Open Access Journals (Sweden)

    Dawn McGee

    2010-01-01

    Full Text Available Background. Alpha-1 antitrypsin deficiency (AAT is an inherited condition that predisposes to lung and/or liver disease. Objective. The current study examined the clinical features of the PiSS genotype. Methods. Nineteen study participants (PiSS and 29 matched control participants (PiMM were telephone interviewed using a standardized questionnaire. Demographic features, cigarette smoking, vocation, medication history, and clinical diagnoses were compared. Statistical analysis was performed. Finally, a comprehensive literature review was performed by two investigators. Results. 12/19 (63.2% study participants reported the presence of lung and/or liver disease compared to 12/29 (41.4% control participants. There trended toward having a higher frequency of medication allergies in the study population (42.11% versus 20.69%. Conclusions. The PiSS genotype was associated with a similar incidence of obstructive lung disease to controls. Selective bias intrinsic in testing for AAT deficiency and the rarity of the PiSS genotype will make future study of this association dependent on population-based tests.

  15. Mannose-binding lectin deficiency and acute exacerbations of chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    Woodruff PG

    2012-11-01

    Full Text Available Richard K Albert,1 John Connett,2 Jeffrey L Curtis,3,4 Fernando J Martinez,3 MeiLan K Han,3 Stephen C Lazarus,5 Prescott G Woodruff51Medicine Service, Denver Health and Department of Medicine, University of Colorado Denver, Denver, CO, 2Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, MN, 3Pulmonary and Critical Care Medicine, Department of Medicine, University of Michigan, Ann Arbor, MI, 4Pulmonary and Critical Care Medicine, VA Medical Center, Ann Arbor, MI, 5Pulmonary and Critical Care Medicine, Department of Medicine, and Cardiovascular Research Institute, University of California, San Francisco, CA, USABackground: Mannose-binding lectin is a collectin involved in host defense against infection. Whether mannose-binding lectin deficiency is associated with acute exacerbations of chronic obstructive pulmonary disease is debated.Methods: Participants in a study designed to determine if azithromycin taken daily for one year decreased acute exacerbations had serum mannose-binding lectin concentrations measured at the time of enrollment.Results: Samples were obtained from 1037 subjects (91% in the trial. The prevalence of mannose-binding lectin deficiency ranged from 0.5% to 52.2%, depending on how deficiency was defined. No differences in the prevalence of deficiency were observed with respect to any demographic variable assessed, and no differences were observed in time to first exacerbation, rate of exacerbations, or percentage of subjects requiring hospitalization for exacerbations in those with deficiency versus those without, regardless of how deficiency was defined.Conclusion: In a large sample of subjects with chronic obstructive pulmonary disease selected for having an increased risk of experiencing an acute exacerbation of chronic obstructive pulmonary disease, only 1.9% had mannose-binding lectin concentrations below the normal range and we found no association between mannose-binding lectin

  16. Primary coenzyme Q deficiency in Pdss2 mutant mice causes isolated renal disease.

    Directory of Open Access Journals (Sweden)

    Min Peng

    2008-04-01

    Full Text Available Coenzyme Q (CoQ is an essential electron carrier in the respiratory chain whose deficiency has been implicated in a wide variety of human mitochondrial disease manifestations. Its multi-step biosynthesis involves production of polyisoprenoid diphosphate in a reaction that requires the enzymes be encoded by PDSS1 and PDSS2. Homozygous mutations in either of these genes, in humans, lead to severe neuromuscular disease, with nephrotic syndrome seen in PDSS2 deficiency. We now show that a presumed autoimmune kidney disease in mice with the missense Pdss2(kd/kd genotype can be attributed to a mitochondrial CoQ biosynthetic defect. Levels of CoQ9 and CoQ10 in kidney homogenates from B6.Pdss2(kd/kd mutants were significantly lower than those in B6 control mice. Disease manifestations originate specifically in glomerular podocytes, as renal disease is seen in Podocin/cre,Pdss2(loxP/loxP knockout mice but not in conditional knockouts targeted to renal tubular epithelium, monocytes, or hepatocytes. Liver-conditional B6.Alb/cre,Pdss2(loxP/loxP knockout mice have no overt disease despite demonstration that their livers have undetectable CoQ9 levels, impaired respiratory capacity, and significantly altered intermediary metabolism as evidenced by transcriptional profiling and amino acid quantitation. These data suggest that disease manifestations of CoQ deficiency relate to tissue-specific respiratory capacity thresholds, with glomerular podocytes displaying the greatest sensitivity to Pdss2 impairment.

  17. A β Damages Learning and Memory in Alzheimer's Disease Rats with Kidney-Yang Deficiency

    OpenAIRE

    Qi, Dongmei; Qiao, Yongfa; Zhang, Xin; Yu, Huijuan; Cheng, Bin; Qiao, Haifa

    2012-01-01

    Previous studies demonstrated that Alzheimer's disease was considered as the consequence produced by deficiency of Kidney essence. However, the mechanism underlying the symptoms also remains elusive. Here we report that spatial learning and memory, escape, and swimming capacities were damaged significantly in Kidney-yang deficiency rats. Indeed, both hippocampal A β 40 and 42 increases in Kidney-yang deficiency contribute to the learning and memory impairments. Specifically, damage of synapti...

  18. Anemia and Iron Deficiency in Children With Potential Celiac Disease.

    Science.gov (United States)

    Repo, Marleena; Lindfors, Katri; Mäki, Markku; Huhtala, Heini; Laurila, Kaija; Lähdeaho, Marja-Leena; Saavalainen, Päivi; Kaukinen, Katri; Kurppa, Kalle

    2017-01-01

    Active screening for celiac disease frequently detects seropositive children with normal villous morphology (potential celiac disease). It remains unclear whether these subjects should be treated. We here investigated the prevalence of anemia and iron deficiency in children with potential and mucosal atrophy celiac disease. The prospective study involved 19 children with potential disease, 67 with partial or subtotal villous atrophy (P/SVA), and 16 with total villous atrophy (TVA). Twenty-three healthy children comprised the control group. The groups were compared for various clinical, histological, and laboratory parameters and hepcidin. The prevalence of abnormal parameters was as follows (controls, potential celiac disease, P/SVA, and TVA, respectively): anemia 0%, 15%, 22%, and 63%; low iron 5%, 0%, 14%, and 50%; increased transferrin receptor 1 5%, 16%, 20%, and 47%; low ferritin 0%, 21%, 35%, and 87%; and low transferrin saturation 10%, 11%, 41%, and 71%. One subject had low folate and none had low vitamin B12. The median values for hemoglobin, total iron, ferritin, and transferrin saturation were significantly lower and transferrin receptor 1 values higher in TVA group compared with other groups. After a median of 7 months on a gluten-free diet hemoglobin, total iron, ferritin, and albumin in children with P/SVA exceeded the baseline values in the potential celiac disease group. The development of anemia and iron deficiency in celiac disease is a continuum and may already be present in children with normal villous morphology, advocating an early diagnosis and possible dietary treatment of these patients.

  19. Links between Vitamin D Deficiency and Cardiovascular Diseases

    Directory of Open Access Journals (Sweden)

    Ioana Mozos

    2015-01-01

    Full Text Available The aim of the present paper was to review the most important mechanisms explaining the possible association of vitamin D deficiency and cardiovascular diseases, focusing on recent experimental and clinical data. Low vitamin D levels favor atherosclerosis enabling vascular inflammation, endothelial dysfunction, formation of foam cells, and proliferation of smooth muscle cells. The antihypertensive properties of vitamin D include suppression of the renin-angiotensin-aldosterone system, renoprotective effects, direct effects on endothelial cells and calcium metabolism, inhibition of growth of vascular smooth muscle cells, prevention of secondary hyperparathyroidism, and beneficial effects on cardiovascular risk factors. Vitamin D is also involved in glycemic control, lipid metabolism, insulin secretion, and sensitivity, explaining the association between vitamin D deficiency and metabolic syndrome. Vitamin D deficit was associated in some studies with the number of affected coronary arteries, postinfarction complications, inflammatory cytokines and cardiac remodeling in patients with myocardial infarction, direct electromechanical effects and inflammation in atrial fibrillation, and neuroprotective effects in stroke. In peripheral arterial disease, vitamin D status was related to the decline of the functional performance, severity, atherosclerosis and inflammatory markers, arterial stiffness, vascular calcifications, and arterial aging. Vitamin D supplementation should further consider additional factors, such as phosphates, parathormone, renin, and fibroblast growth factor 23 levels.

  20. The association of vitamin D deficiency with non-alcoholic fatty liver disease

    OpenAIRE

    Küçükazman, Metin; Ata, Naim; Dal, Kürşat; Yeniova, Abdullah Özgür; Kefeli, Ayşe; Basyigit, Sebahat; Aktas, Bora; Akin, Kadir Okhan; Ağladioğlu, Kadir; Üre, Öznur Sari; Topal, Firdes; Nazligül, Yaşar; Beyan, Esin; Ertugrul, Derun Taner

    2014-01-01

    OBJECTIVE: Vitamin D deficiency has been related to diabetes, hypertension, hyperlipidemia and peripheral vascular disease. In this study, we aimed to investigate the role of vitamin D status in non-alcoholic fatty liver disease. METHODS: We included 211 consecutive subjects to examine the presence of non-alcoholic fatty liver disease. Of these subjects, 57 did not have non-alcoholic fatty liver disease and 154 had non-alcoholic fatty liver disease. RESULTS: The non-alcoholic fatty liver ...

  1. Current opinion on the management of iron deficiency anaemia in gastrointestinal diseases.

    Science.gov (United States)

    Derovs, Aleksejs; Pokrotnieks, Juris; Derova, Jelena; Danilans, Anatolijs; Pukitis, Aldis; Dombure, Polina; Leiniece, Sandra; Zeltina Indra

    2014-01-01

    Iron deficiency is the most common cause of anaemia in the world. Despite frequently weak and masked clinical presentation of iron deficiency anaemia (IDA), this disease is very serious with complications leading to early mortality. In the developed countries IDA is predominantly diagnosed as the complication of another disease or as the result of major bleeding events. Diagnosis of IDA should be based on laboratory findings i.e. haemoglobin, mean corpuscular hemoglobin concentration and ferritin. Latter is the most sensitive marker for iron deficiency. Anaemia of chronic disease should be taken into an account as a potential differential diagnosis or coexisting state. For women in fertility age with IDA, gynaecological disorders should be ruled out first. Males and postmenopausal women with IDA should undergo upper, lower and in certain cases capsule endoscopy and/or enteroscopy to find a plausible cause of IDA. The ultimate goal of therapy is to find out and treat the primary cause of IDA. Iron body stores should be restored using either oral or parenteral iron preparations. The use of parenteral iron preparations in patients with gastrointestinal pathologies is often clinically substantiated for the treatment of IDA. Red blood cell transfusion should be administered in emergency cases only.

  2. Reduced MLH3 Expression in the Syndrome of Gan-Shen Yin Deficiency in Patients with Different Diseases.

    Science.gov (United States)

    Du, Juan; Zhong, Maofeng; Liu, Dong; Liang, Shufang; Liu, Xiaolin; Cheng, Binbin; Zhang, Yani; Yin, Zifei; Wang, Yuan; Ling, Changquan

    2017-01-01

    Traditional Chinese medicine formulates treatment according to body constitution (BC) differentiation. Different constitutions have specific metabolic characteristics and different susceptibility to certain diseases. This study aimed to assess the characteristic genes of gan-shen Yin deficiency constitution in different diseases. Fifty primary liver cancer (PLC) patients, 94 hypertension (HBP) patients, and 100 diabetes mellitus (DM) patients were enrolled and classified into gan-shen Yin deficiency group and non-gan-shen Yin deficiency group according to the body constitution questionnaire to assess the clinical manifestation of patients. The mRNA expressions of 17 genes in PLC patients with gan-shen Yin deficiency were different from those without gan-shen Yin deficiency. However, considering all patients with PLC, HBP, and DM, only MLH3 was significantly lower in gan-shen Yin deficiency group than that in non-gen-shen Yin deficiency. By ROC analysis, the relationship between MLH3 and gan-shen Yin deficiency constitution was confirmed. Treatment of MLH3 (-/- and -/+) mice with Liuweidihuang wan, classical prescriptions for Yin deficiency, partly ameliorates the body constitution of Yin deficiency in MLH3 (-/+) mice, but not in MLH3 (-/-) mice. MLH3 might be one of material bases of gan-shen Yin deficiency constitution.

  3. Spontaneous growth in growth hormone deficiency from birth until 7 years of age: development of disease-specific growth curves.

    Science.gov (United States)

    Mayer, M; Schmitt, K; Kapelari, K; Frisch, H; Köstl, G; Voigt, M

    2010-01-01

    Little is known about spontaneous growth of growth hormone (GH)-deficient children during infancy and childhood. Retrospectively, we calculated disease-specific pretreatment percentiles for height, weight, BMI and growth velocity of 113 GH-deficient boys and 41 GH-deficient girls from birth until 7 years of age, by mean and standard deviation. Infants with idiopathic GH deficiency (GHD) grow in disease-specific percentile channels. There is a significant difference in length and weight from birth onward compared to regional reference (pgrowth velocity, despite a wide variance in the first years, so height deficit became more evident with increasing age. GHD is a congenital disease no matter when height deficit becomes clinically evident, because GH-deficient children grow in disease-specific percentile channels with a highly significantly reduced length and weight, which demonstrates that GH is essential for adequate growth in infancy and early childhood. Copyright (c) 2010 S. Karger AG, Basel.

  4. Hemolysis, myopathy, and cardiac disease associated with hereditary phosphofructokinase deficiency in two Whippets

    Science.gov (United States)

    Gerber, Karen; Harvey, John W.; D'Agorne, Sara; Wood, Jonathan; Giger, Urs

    2009-01-01

    Two male castrated Whippet littermates were presented at 1 year of age for pallor, tachycardia, systolic heart murmur, dark yellow to orange feces, intermittent lethargy, pigmenturia, and muscle shivering or cramping after exercise. Persistent macrocytic hypochromic anemia with marked reticulocytosis and metarubricytosis was found when CBC results were compared with reference values for Whippets. Increased serum creatine kinase activity and hyperkalemia also were sometimes present over the 4-year period of evaluation. Progressively increasing serum concentrations of N-terminal prohormone brain natriuretic peptide suggested cardiac disease. Erythrocytes from the whippets were less osmotically fragile but more alkaline fragile than those from control dogs. Erythrocyte phosphofructokinase (PFK) activities and 2,3-diphosphoglycerate concentrations were decreased. Restriction enzyme-based DNA test screening and DNA sequencing revealed the same mutation in the muscle-PFK gene of the Whippets as seen in English Springer Spaniel dogs with PFK deficiency. This is the first report of PFK deficiency in Whippet dogs. In addition to causing hemolysis and exertional myopathy, heart disease may be a prominent clinical component of PFK deficiency in this breed and has not been previously recognized in PFK-deficient English Springer Spaniels. PMID:19228357

  5. 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 ...

  6. Iron isomaltoside 1000: a new intravenous iron for treating iron deficiency in chronic kidney disease

    DEFF Research Database (Denmark)

    Wikström, Björn; Bhandari, Sunil; Barany, Peter

    2011-01-01

    Patients with chronic kidney disease (CKD) often suffer from iron deficiency anemia necessitating treatment with intravenous iron. This study was designed to assess the safety of iron isomaltoside 1000 (Monofer) in CKD patients. The secondary objective was to assess its effect on iron deficiency...... anemia....

  7. Thiamine and magnesium deficiencies: keys to disease.

    Science.gov (United States)

    Lonsdale, D

    2015-02-01

    Thiamine deficiency (TD) is accepted as the cause of beriberi because of its action in the metabolism of simple carbohydrates, mainly as the rate limiting cofactor for the dehydrogenases of pyruvate and alpha-ketoglutarate, both being critical to the action of the citric acid cycle. Transketolase, dependent on thiamine and magnesium, occurs twice in the oxidative pentose pathway, important in production of reducing equivalents. Thiamine is also a cofactor in the dehydrogenase complex in the degradation of the branched chain amino acids, leucine, isoleucine and valine. In spite of these well accepted facts, the overall clinical effects of TD are still poorly understood. Because of the discovery of 2-hydroxyacyl-CoA lyase (HACL1) as the first peroxisomal enzyme in mammals found to be dependent on thiamine pyrophosphate (TPP) and the ability of thiamine to bind with prion protein, these factors should improve our clinical approach to TD. HACL1 has two important roles in alpha oxidation, the degradation of phytanic acid and shortening of 2-hydroxy long-chain fatty acids so that they can be degraded further by beta oxidation. The downstream effects of a lack of efficiency in this enzyme would be expected to be critical in normal brain metabolism. Although TD has been shown experimentally to produce reversible damage to mitochondria and there are many other causes of mitochondrial dysfunction, finding TD as the potential biochemical lesion would help in differential diagnosis. Stresses imposed by infection, head injury or inoculation can initiate intermittent cerebellar ataxia in thiamine deficiency/dependency. Medication or vaccine reactions appear to be more easily initiated in the more intelligent individuals when asymptomatic marginal malnutrition exists. Erythrocyte transketolase testing has shown that thiamine deficiency is widespread. It is hypothesized that the massive consumption of empty calories, particularly those derived from carbohydrate and fat, results in

  8. Anemia of Chronic Disease and Iron Deficiency Anemia in Inflammatory Bowel Diseases: Pathophysiology, Diagnosis, and Treatment.

    Science.gov (United States)

    Murawska, Natalia; Fabisiak, Adam; Fichna, Jakub

    2016-05-01

    Anemia coexists with inflammatory bowel disease (IBD) in up to two-thirds of patients, significantly impairing quality of life. The most common types of anemia in patients with IBD are iron deficiency anemia and anemia of chronic disease, which often overlap. In most cases, available laboratory tests allow successful diagnosis of iron deficiency, where difficulties appear, recently established indices such as soluble transferrin-ferritin ratio or percentage of hypochromic red cells are used. In this review, we discuss the management of the most common types of anemia in respect of the latest available data. Thus, we provide the mechanisms underlying pathophysiology of these entities; furthermore, we discuss the role of hepcidin in developing anemia in IBD. Next, we present the treatment options for each type of anemia and highlight the importance of individual choice of action. We also focus on newly developed intravenous iron preparations and novel, promising drug candidates targeting hepcidin. Concurrently, we talk about difficulties in differentiating between the true and functional iron deficiency, and discuss tools facilitating the process. Finally, we emphasize the importance of proper diagnosis and treatment of anemia in IBD. We conclude that management of anemia in patients with IBD is tricky, and appropriate screening of patients regarding anemia is substantial.

  9. An update on the association of vitamin D deficiency with common infectious diseases.

    Science.gov (United States)

    Watkins, Richard R; Lemonovich, Tracy L; Salata, Robert A

    2015-05-01

    Vitamin D plays an important role in modulating the immune response to infections. Deficiency of vitamin D is a common condition, affecting both the general population and patients in health care facilities. Over the last decade, an increasing body of evidence has shown an association between vitamin D deficiency and an increased risk for acquiring several infectious diseases, as well as poorer outcomes in vitamin D deficient patients with infections. This review details recent developments in understanding the role of vitamin D in immunity, the antibacterial actions of vitamin D, the association between vitamin D deficiency and common infections (like sepsis, pneumonia, influenza, methicillin-resistant Staphylococcus aureus, human immunodeficiency virus type-1 (HIV), and hepatitis C virus (HCV)), potential therapeutic implications for vitamin D replacement, and future research directions.

  10. Seronegative Celiac Disease and Immunoglobulin Deficiency: Where to Look in the Submerged Iceberg?

    Directory of Open Access Journals (Sweden)

    Floriana Giorgio

    2015-09-01

    Full Text Available In the present narrative review, we analyzed the relationship between seronegative celiac disease (SNCD and immunoglobulin deficiencies. For this purpose, we conducted a literature search on the main medical databases. SNCD poses a diagnostic dilemma. Villous blunting, intraepithelial lymphocytes (IELs count and gluten “challenge” are the most reliable markers. Immunohistochemistry/immunofluorescence tissue transglutaminase (tTG-targeted mucosal immunoglobulin A (IgA immune complexes in the intestinal mucosa of SNCD patients may be useful. In our experience, tTG-mRNA was similarly increased in seropositive celiac disease (CD and suspected SNCD, and strongly correlated with the IELs count. This increase is found even in the IELs’ range of 15–25/100 enterocytes, suggesting that there may be a “grey zone” of gluten-related disorders. An immune deregulation (severely lacking B-cell differentiation underlies the association of SNCD with immunoglobulin deficiencies. Therefore, CD may be linked to autoimmune disorders and immune deficits (common variable immunodeficiency (CVID/IgA selective deficiency. CVID is a heterogeneous group of antibodies dysfunction, whose association with CD is demonstrated only by the response to a gluten-free diet (GFD. We hypothesized a familial inheritance between CD and CVID. Selective IgA deficiency, commonly associated with CD, accounts for IgA-tTG seronegativity. Selective IgM deficiency (sIgMD is rare (<300 cases and associated to CD in 5% of cases. We diagnosed SNCD in a patient affected by sIgMD using the tTG-mRNA assay. One-year GFD induced IgM restoration. This evidence, supporting a link between SNCD and immunoglobulin deficiencies, suggests that we should take a closer look at this association.

  11. Protean manifestations of vitamin D deficiency, part 3: association with cardiovascular disease and disorders of the central and peripheral nervous systems.

    Science.gov (United States)

    Bell, David S H

    2011-05-01

    Vitamin D deficiency is associated with the risk factors of inflammation, insulin resistance and endothelial dysfunction, and left ventricular hypertrophy. As a result there is an increase in cardiovascular events (CVEs) associated with vitamin D deficiency. Vitamin D deficiency itself or secondary hyperparathyroidism or both may be responsible for the increase in CVEs. Correction of vitamin D deficiency may decrease the incidence of CVEs. Vitamin D deficiency is also associated with Alzheimer disease, schizophrenia, depression, and chronic pain and muscle weakness. Vitamin D deficiency is early treated with oral vitamin D supplements which may improve the manifestations of the diseases associated with vitamin D deficiency.

  12. Iron-Deficiency Anemia

    Medline Plus

    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 ...

  13. [Strategies to promote testosterone deficiency syndrome: a paradigm of disease mongering].

    Science.gov (United States)

    Gavilán, Enrique; Jiménez de Gracia, Laura; Gérvas, Juan

    2014-01-01

    The so-called «testosterone deficiency syndrome» is a blend of nonspecific symptoms typical of the physiological process of aging. This syndrome has been the subject of intense promotional activity that has presented the phenomenon as highly prevalent and with a major public health impact. This strategy has been accompanied by the emergence of new and easy to administer testosterone devices into the pharmaceutical market and has generated significant sales for drug companies. The commercial promotion of testosterone deficiency syndrome and its remedies has exploited cultural stereotypes of aging and sexuality through awareness campaigns promoted by the laboratories involved and has been disseminated by media with the participation of numerous experts and with the support of scientific associations, representing a paradigmatic case of disease mongering. This example might be of use in the response to disease mongering activities from the clinical and public health fields. Copyright © 2013 SESPAS. Published by Elsevier Espana. All rights reserved.

  14. Rheumatoid arthritis disease activity and vitamin D deficiency in an Asian resident population.

    Science.gov (United States)

    Quraishi, Mohammed K; Badsha, Humeira

    2016-04-01

    We aimed to assess the prevalence of vitamin D deficiency and its association with rheumatoid arthritis (RA) disease activity in a UAE population. Forty-five consecutive subjects were prospectively recruited during the early summer with their clinical examination and Health Assessment Questionnaire (HAQ) being recorded at a clinic appointment, along with their blood sample being taken for the 25-hydroxyvitamin D (25(OH)D) total test. Thirty-five (76%) patients claimed to be exposed to sunlight for Disease Activity Score (DAS28) or HAQ scores. A direct relationship was observed between HAQ scores and DAS28 scores (P culture. No association was observed between vitamin D and disease activity. However, the high prevalence of vitamin D deficiency may negatively impact on bone health of these patients in the future. © 2013 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

  15. Autophagy deficiency in macrophages enhances NLRP3 inflammasome activity and chronic lung disease following silica exposure

    International Nuclear Information System (INIS)

    Jessop, Forrest; Hamilton, Raymond F.; Rhoderick, Joseph F.; Shaw, Pamela K.; Holian, Andrij

    2016-01-01

    Autophagy is an important metabolic mechanism that can promote cellular survival following injury. The specific contribution of autophagy to silica-induced inflammation and disease is not known. The objective of these studies was to determine the effects of silica exposure on the autophagic pathway in macrophages, as well as the general contribution of autophagy in macrophages to inflammation and disease. Silica exposure enhanced autophagic activity in vitro in Bone Marrow derived Macrophages and in vivo in Alveolar Macrophages isolated from silica-exposed mice. Impairment of autophagy in myeloid cells in vivo using Atg5 fl/fl LysM-Cre + mice resulted in enhanced cytotoxicity and inflammation after silica exposure compared to littermate controls, including elevated IL-18 and the alarmin HMGB1 in the whole lavage fluid. Autophagy deficiency caused some spontaneous inflammation and disease. Greater silica-induced acute inflammation in Atg5 fl/fl LysM-Cre + mice correlated with increased fibrosis and chronic lung disease. These studies demonstrate a critical role for autophagy in suppressing silica-induced cytotoxicity and inflammation in disease development. Furthermore, this data highlights the importance of basal autophagy in macrophages and other myeloid cells in maintaining lung homeostasis. - Highlights: • Silica exposure increases autophagy in macrophages. • Autophagy deficient mice have enhanced inflammation and silicosis. • Autophagy deficiency in macrophages results in greater silica-induced cytotoxicity. • Autophagy deficiency in macrophages increases extracellular IL-18 and HMGB1.

  16. Iron Deficiency Anemia in Adult Onset Still's Disease with a Serum Ferritin of 26,387 μg/L

    Directory of Open Access Journals (Sweden)

    Sheetal Patel

    2011-01-01

    Full Text Available Serum ferritin rises in the anemia of chronic inflammation reflecting increased iron storage and other changes mediated by inflammation. When iron deficiency coexists, the ferritin may not always decline into the subnormal range. We describe the rare interaction of iron deficiency with the extreme hyperferritinemia characteristic of adult onset Still's disease. The combination has clinical relevance and allows deductions about the presence of serum ferritin at 26,387 μg/L despite obvious iron depletion. The diagnosis of iron deficiency anemia was delayed and became fully obvious when her Still's disease remitted and serum ferritin decreased to 6.5 μg/L. The coexistence of iron deficiency should be considered when evaluating a patient with anemia of chronic inflammation even when the ferritin level is elevated several hundredfold. Further insights on ferritin metabolism in Still's disease are suggested by the likelihood that the patient's massive hyperferritinemia in the acute phase of Still's disease was almost entirely of the iron-free apoferritin form.

  17. Progressive dopamine and hypocretin deficiencies in Parkinson's disease: is there an impact on sleep and wakefulness?

    Science.gov (United States)

    Wienecke, Miriam; Werth, Esther; Poryazova, Rositsa; Baumann-Vogel, Heide; Bassetti, Claudio L; Weller, Michael; Waldvogel, Daniel; Storch, Alexander; Baumann, Christian R

    2012-12-01

    Sleep-wake disturbances are frequent in patients with Parkinson's disease, but prospective controlled electrophysiological studies of sleep in those patients are surprisingly sparse, and the pathophysiology of sleep-wake disturbances in Parkinson's disease remains largely elusive. In particular, the impact of impaired dopaminergic and hypocretin (orexin) signalling on sleep and wakefulness in Parkinson's disease is still unknown. We performed a prospective, controlled electrophysiological study in patients with early and advanced Parkinson's disease, e.g. in subjects with presumably different levels of dopamine and hypocretin cell loss. We compared sleep laboratory tests and cerebrospinal fluid levels with hypocretin-deficient patients with narcolepsy with cataplexy, and with matched controls. Nocturnal sleep efficiency was most decreased in advanced Parkinson patients, and still lower in early Parkinson patients than in narcolepsy subjects. Excessive daytime sleepiness was most severe in narcolepsy patients. In Parkinson patients, objective sleepiness correlated with decrease of cerebrospinal fluid hypocretin levels, and repeated hypocretin measurements in two Parkinson patients revealed a decrease of levels over years. This suggests that dopamine and hypocretin deficiency differentially affect sleep and wakefulness in Parkinson's disease. Poorer sleep quality is linked to dopamine deficiency and other disease-related factors. Despite hypocretin cell loss in Parkinson's disease being only partial, disturbed hypocretin signalling is likely to contribute to excessive daytime sleepiness in Parkinson patients. © 2012 European Sleep Research Society.

  18. Sociodemographic and Cultural Determinants of Sleep Deficiency: Implications for Cardiometabolic Disease Risk

    OpenAIRE

    Knutson, Kristen L.

    2012-01-01

    Sleep is a biological imperative associated with cardiometabolic disease risk. As such, a thorough discussion of the sociocultural and demographic determinants of sleep is warranted, if not overdue. This paper begins with a brief review of the laboratory and epidemiologic evidence linking sleep deficiency, which includes insufficient sleep and poor sleep quality, with increased risk of chronic cardiometabolic diseases such as obesity, diabetes and hypertension. Identification of the determina...

  19. Is PiSS Alpha-1 Antitrypsin Deficiency Associated with Disease?

    OpenAIRE

    McGee, Dawn; Schwarz, Laura; McClure, Rebecca; Peterka, Lauren; Rouhani, Farshid; Brantly, Mark; Strange, Charlie

    2010-01-01

    Background. Alpha-1 antitrypsin deficiency (AAT) is an inherited condition that predisposes to lung and/or liver disease. Objective. The current study examined the clinical features of the PiSS genotype. Methods. Nineteen study participants (PiSS) and 29 matched control participants (PiMM) were telephone interviewed using a standardized questionnaire. Demographic features, cigarette smoking, vocation, medication history, and clinical diagnoses were compared. Statistical analysis was perform...

  20. Vitamin D deficiency in Crohn's disease: prevalence, risk factors and supplement use in an outpatient setting.

    LENUS (Irish Health Repository)

    Suibhne, Treasa Nic

    2012-03-01

    Vitamin D deficiency impacts on bone health and has potential new roles in inflammation. We aimed to determine the prevalence of and risk factors for vitamin D deficiency and to explore vitamin D supplement usage in patients with Crohn\\'s disease (CD) in an outpatient setting, compared with controls.

  1. Genetically Determined MBL Deficiency Is Associated with Protection against Chronic Cardiomyopathy in Chagas Disease.

    Directory of Open Access Journals (Sweden)

    Paola Rosa Luz

    2016-01-01

    Full Text Available Chagas disease (CD is caused by Trypanosoma cruzi, whose sugar moieties are recognized by mannan binding lectin (MBL, a soluble pattern-recognition molecule that activates the lectin pathway of complement. MBL levels and protein activity are affected by polymorphisms in the MBL2 gene. We sequenced the MBL2 promoter and exon 1 in 196 chronic CD patients and 202 controls. The MBL2*C allele, which causes MBL deficiency, was associated with protection against CD (P = 0.007, OR = 0.32. Compared with controls, genotypes with this allele were completely absent in patients with the cardiac form of the disease (P = 0.003. Furthermore, cardiac patients with genotypes causing MBL deficiency presented less heart damage (P = 0.003, OR = 0.23, compared with cardiac patients having the XA haplotype causing low MBL levels, but fully capable of activating complement (P = 0.005, OR = 7.07. Among the patients, those with alleles causing MBL deficiency presented lower levels of cytokines and chemokines possibly implicated in symptom development (IL9, p = 0.013; PDGFB, p = 0.036 and RANTES, p = 0.031. These findings suggest a protective effect of genetically determined MBL deficiency against the development and progression of chronic CD cardiomyopathy.

  2. The Prevalence of Thyroid Disease in the Children and Teenagers in Iodine-Deficient Region

    Directory of Open Access Journals (Sweden)

    A V Kiyaev

    2007-06-01

    Full Text Available To indicate iodine intake and the prevalence of thyroid disease in the iodine-deficient area we perform complex investigation of 2332 children and teenagers in 23 settlements of Sverdlovsk region. Studying population consisted of1153 7—8 years old children (599 girls and 554 boys and 1179 14—15 years old teenagers (637 girls and 542 boys. Study protocol includes thyroid ultrasound for all children and urinary iodine excretion for younger group and, serum TSH, AT-TG and AT-TPO in older group. The incidence of diffuse goiter was 22.8% and median of urinary iodine excretion was 53 μg/l. We found that Sverdlovsk region is a mild iodine-deficient area. The incidence of significant thyroid diseases is relatively low (thyroid cancer, functional autonomy and overt hypothyroidism — in 0.04%, nodular goiter — 0.26%, autoimmune thyroiditis with subclinical hypothyroidism — 0.6%. There is no significant difference in the prevalence of thyroid disease among children and teenagers. We found that thyroid ultrasound is not a reasonable screening strategy for thyroid cancer and nodular goiter in pediatric population of the iodine-deficient region. We consider that the most reasonable screening strategy is the palpation technique.

  3. White muscle disease in three selenium deficient beef and dairy calves in Argentina and Uruguay

    Directory of Open Access Journals (Sweden)

    Alejandro Martín Rodriguez

    2018-05-01

    Full Text Available ABSTRACT: White muscle disease (WMD, nutritional myodegeneration or enzootic muscular dystrophy, is a nutritional condition associated with selenium and/or vitamin E deficiency in ruminants. These elements are constituents of the major body antioxidant systems. Depletion of selenium results in oxidative damage to cardiac and skeletal muscle cells, resulting in myodegeneration and myonecrosis, typical lesions of WMD. Selenium deficiency is common in South America, but WMD is underreported. This research describes clinical, biochemical and pathological findings in two episodes of WMD associated with selenium deficiency in beef and dairy calves in Argentina and Uruguay with concurrent copper deficiency in one of them, which resulted in spontaneous calf mortality. Further studies are necessary to estimate the true incidence and economic impact of clinical and subclinical mineral deficiencies in livestock production systems in the southern cone of South America.

  4. Is there any difference between Vitamin D deficiency among heart failure and Non-heart failure elderly with cardiovascular disease?

    Directory of Open Access Journals (Sweden)

    Zohreh Taraghi

    2016-02-01

    Full Text Available Vitamin D deficiency is common among the elderly with and without heart failure (HF. This study was designed to identify the degree of vitamin D deficiency among HF and Non- HF elderly with cardiovascular disease. In this study, fifty hospitalized elderly patients with HF (26 women and 24 men, age range 60-90 years and fifty elderly without HF were randomly selected. The level of serum 25-hydroxy vitamin D was measured using the Eliza method. There were no significantly difference between two groups regarding to the mean age, living location, life style parameters, mean years of disease involvement and disease severity, cardiovascular risk factors and co-morbidities, except for renal problems(P=0/039, hemoglobin levels(P=0/044, and creatinine levels (P=0/048. In both groups, the majority of patients, were moderately vitamin D deficient and there was no significantly difference between two groups. Considering the high prevalence of vitamin D deficiency among HF and Non-HF elderly with cardiovascular disease, its monitoring and correcting seems essential.

  5. Mitochondrial DNA Depletion in Respiratory Chain–Deficient Parkinson Disease Neurons

    Science.gov (United States)

    Rygiel, Karolina A.; Hepplewhite, Philippa D.; Morris, Christopher M.; Picard, Martin; Turnbull, Doug M.

    2016-01-01

    Objective To determine the extent of respiratory chain abnormalities and investigate the contribution of mtDNA to the loss of respiratory chain complexes (CI–IV) in the substantia nigra (SN) of idiopathic Parkinson disease (IPD) patients at the single‐neuron level. Methods Multiple‐label immunofluorescence was applied to postmortem sections of 10 IPD patients and 10 controls to quantify the abundance of CI–IV subunits (NDUFB8 or NDUFA13, SDHA, UQCRC2, and COXI) and mitochondrial transcription factors (TFAM and TFB2M) relative to mitochondrial mass (porin and GRP75) in dopaminergic neurons. To assess the involvement of mtDNA in respiratory chain deficiency in IPD, SN neurons, isolated with laser‐capture microdissection, were assayed for mtDNA deletions, copy number, and presence of transcription/replication‐associated 7S DNA employing a triplex real‐time polymerase chain reaction (PCR) assay. Results Whereas mitochondrial mass was unchanged in single SN neurons from IPD patients, we observed a significant reduction in the abundances of CI and II subunits. At the single‐cell level, CI and II deficiencies were correlated in patients. The CI deficiency concomitantly occurred with low abundances of the mtDNA transcription factors TFAM and TFB2M, which also initiate transcription‐primed mtDNA replication. Consistent with this, real‐time PCR analysis revealed fewer transcription/replication‐associated mtDNA molecules and an overall reduction in mtDNA copy number in patients. This effect was more pronounced in single IPD neurons with severe CI deficiency. Interpretation Respiratory chain dysfunction in IPD neurons not only involves CI, but also extends to CII. These deficiencies are possibly a consequence of the interplay between nDNA and mtDNA‐encoded factors mechanistically connected via TFAM. ANN NEUROL 2016;79:366–378 PMID:26605748

  6. Unrecognized vitamin D3 deficiency is common in Parkinson disease: Harvard Biomarker Study.

    Science.gov (United States)

    Ding, Hongliu; Dhima, Kaltra; Lockhart, Kaitlin C; Locascio, Joseph J; Hoesing, Ashley N; Duong, Karen; Trisini-Lipsanopoulos, Ana; Hayes, Michael T; Sohur, U Shivraj; Wills, Anne-Marie; Mollenhauer, Brit; Flaherty, Alice W; Hung, Albert Y; Mejia, Nicte; Khurana, Vikram; Gomperts, Stephen N; Selkoe, Dennis J; Schwarzschild, Michael A; Schlossmacher, Michael G; Hyman, Bradley T; Sudarsky, Lewis R; Growdon, John H; Scherzer, Clemens R

    2013-10-22

    To conclusively test for a specific association between the biological marker 25-hydroxy-vitamin D3, a transcriptionally active hormone produced in human skin and liver, and the prevalence and severity of Parkinson disease (PD). We used liquid chromatography/tandem mass spectrometry to establish an association specifically between deficiency of 25-hydroxy-vitamin D3 and PD in a cross-sectional and longitudinal case-control study of 388 patients (mean Hoehn and Yahr stage of 2.1 ± 0.6) and 283 control subjects free of neurologic disease nested in the Harvard Biomarker Study. Plasma levels of 25-hydroxy-vitamin D3 were associated with PD in both univariate and multivariate analyses with p values = 0.0034 and 0.047, respectively. Total 25-hydroxy-vitamin D levels, the traditional composite measure of endogenous and exogenous vitamin D, were deficient in 17.6% of patients with PD compared with 9.3% of controls. Low 25-hydroxy-vitamin D3 as well as total 25-hydroxy-vitamin D levels were correlated with higher total Unified Parkinson's Disease Rating Scale scores at baseline and during follow-up. Our study reveals an association between 25-hydroxy-vitamin D3 and PD and suggests that thousands of patients with PD in North America alone may be vitamin D-deficient. This finding has immediate relevance for individual patients at risk of falls as well as public health, and warrants further investigation into the mechanism underlying this association.

  7. Celiac disease, iron deficiency anaemia, grave's disease, osteopenia and short stature in single patient

    International Nuclear Information System (INIS)

    Radaideh, A.M.

    2015-01-01

    Celiac disease is an intestinal immune mediated disorder, triggered by ingestion of gluten-containing diet in genetically susceptible individuals. The genetic pre-disposition is related to human leukocyte antigen (HLA) class II genes, especially HLA-DQ2 positive patients. The prevalence of celiac disease in high worldwide and it has been estimated to be 1-26% in Western countries. Many auto-immune diseases can be associated with celiac disease including auto-immune thyroid disease; hashimoto thyroiditis and grave's disease. The opposite also appears to be true, celiac disease is found on persons with auto-immune thyroid disorders at high rates than the general population. Celiac disease is also associated with other extraintestinal diseases other the auto-immune diseases like anemia, short stature, metabolic bone disease and others. Screening for celiac disease should be considered in patients with auto-immune thyroid disease, anemia, short stature and metabolic bone disease. The life-long adherence to gluten-free diet is the only cure in celiac disease and can improve the quality of patients life and prevent future complications. This report describes a case of Grave's disease, Iron deficiency anemia, Short stature, Osteopenia, diagnosed to have Celiac disease. (author)

  8. An Unusual Case of Hypercalcemia Associated with Graves’ Disease and Vitamin D Deficiency

    Directory of Open Access Journals (Sweden)

    Evgenia Korytnaya

    2011-01-01

    Full Text Available Objective To present a case of hypercalcemia associated with thyrotoxicosis in a patient with vitamin D deficiency and review biochemical changes during the course of treatment. Methods We report a case, describe the changes in serum calcium, phosphorus, parathyroid hormone in Graves’ disease and concomitant Vitamin D deficiency. We compare our findings to those reported in literature. Results Our patient had hypercalcemia secondary to thyrotoxicosis alone, which was confirmed by low parathyroid hormone level and resolution of hypercalcemia with treatment of thyrotoxicosis. The case was complicated by a concomitant vitamin D deficiency. Serum calcium elevation in patients with thyrotoxicosis occurs secondary to hyperthyroidism alone or due to concurrent hyperparathyroidism. Hypercalcemia from thyrotoxicosis is usually asymptomatic and is related to bone resorption. Vitamin D deficiency can be seen in patients with thyrotoxicosis because of accelerated metabolism, poor intestinal absorption and increased demand during bone restoration phase. Coexistence of hypercalcemia and Vitamin D deficiency in patients with thyrotoxicosis is rare, but possible, and 25-hydroxyvitamin D levels should be checked. The definite treatment for hypercalcemia in thyrotoxicosis is correction of thyroid function. Conclusion Hypercalcemia in thyrotoxicosis should be distinguished from concomitant hyperparathyroidism and confirmed by resolution of hypercalcemia with control of thyrotoxicosis. Patients with hypercalcemia and thyrotoxicosis may also have vitamin D deficiency and 25-OH Vitamin D levels should be checked.

  9. The Relevance of Vitamin and Iron Deficiency in Patients with Inflammatory Bowel Diseases in Patients of the Swiss IBD Cohort.

    Science.gov (United States)

    Madanchi, Matiar; Fagagnini, Stefania; Fournier, Nicolas; Biedermann, Luc; Zeitz, Jonas; Battegay, Edouard; Zimmerli, Lukas; Vavricka, Stephan R; Rogler, Gerhard; Scharl, Michael

    2018-04-13

    Vitamin and iron deficiencies are common in patients with inflammatory bowel disease (IBD) as a result of chronic intestinal inflammation, increase in demand, or dietary restrictions. Here, we assessed the frequency of complications in relation to deficiency of iron, folate acid, and vitamin B12 in patients enrolled in the nationwide Swiss Inflammatory Bowel Disease Cohort Study (SIBDCS). A total of 2666 patients were included in the study, 1558 with Crohn's disease (CD) and 1108 with ulcerative colitis (UC). Iron deficiency anemia was detected in 19.6% of CD patients and 21.6% of UC patients. In CD patients low BMI and nonsmoker status were positively associated with anemia. In both CD and UC, malabsorption syndrome, defined as failure of the GI tract to absorb 1 or more substances from the diet, was found to be significantly associated with anemia (6.2% and 3.8%, respectively) and current steroid use (40% CD, 52.7% UC). In CD patients with ileal (31.7% vs 20%) and colonic (29.9% vs 25%) disease location folate deficiency was significantly higher than in patients with ileocolonic CD or upper GI involvement. In CD patients, vitamin B12 deficiency was associated with the onset of stenosis and intestinal surgery (42.9% vs 32.8% and 46% vs 33% for patients with versus without B12 deficiency). Our data indicate that due to frequent occurrence of deficiency states, regular monitoring and substitution of vitamins and iron are mandatory and may prevent long-term intestinal and extraintestinal complications in IBD patients.

  10. Blood group does not correlate with disease severity in patients with Fabry disease (alpha-galactosidase A deficiency)

    NARCIS (Netherlands)

    Linthorst, Gabor E.; Folman, Claudia C.; Aerts, Johannes M. F. G.; Hollak, Carla E. M.

    2003-01-01

    Blood groups B and P1 are substrates for the lysosomal enzyme alpha-galactosidase A. Therefore, patients with alpha-Gal A deficiency and blood groups B or P1 may exhibit more severe disease. In 48 Fabry patients distribution of blood group was not different from that in the Dutch population. No

  11. Vitamin D deficiency in Crohn's disease and healthy controls: a prospective case-control study in the Netherlands

    NARCIS (Netherlands)

    de Bruyn, Jessica R.; van Heeckeren, Rosanne; Ponsioen, Cyriel Y.; van den Brink, Gijs R.; Löwenberg, Mark; Bredenoord, Albert J.; Frijstein, Gerard; D'Haens, Geert R.

    2014-01-01

    Vitamin D deficiency has been observed in a wide range of medical conditions including Crohn's disease (CD). We aimed to assess whether CD patients have lower vitamin D levels than healthy controls, and to determine risk factors for vitamin D deficiency. 25(OH)D was measured by chemiluminescent

  12. [Neonatal screening of hemoglobinopathies and G6PD deficiency in Catalonia (Spain). Molecular study of sickle cell disease associated with alpha thalassemia and G6PD deficiency].

    Science.gov (United States)

    Mañú Pereira, María Del Mar; Cabot, Anna; Martínez González, Ana; Sitjà Navarro, Eulalia; Cararach, Vicent; Sabrià, Josep; Boixaderas, Jordi; Teixidor, Roser; Bosch, Albert; López Vílchez, M Angeles; Martín Ibáñez, Itziar; Carrión, Teresa; Plaja, Pere; Sánchez, Mario; Vives Corrons, José Luis

    2007-06-30

    The prevalence of hemoglobinopathies and glucose-6-phosphate dehidrogenase (G6PD) deficiency in the Catalan neonatal population is increasing due to immigration. Coinheritance of more than a single RBC genetic defect is becoming more frequent and diagnostic pitfalls are also increasing. We intended to demonstrate the need to perform an early diagnosis of sickle cell disease (SCD) by means of neonatal screening, to establish the prevalence of SCD associated with alpha thalassemia and G6PD deficiency and to identify genotypes associated with sickle cell disease and G6PD deficiency. 4,020 blood samples from newborns were screened. For the screening of hemoglobinopathies the high performance liquid chromatography method was used and for G6PD deficiency the fluorescent spot test was employed. We studied the association between betaS gene and alpha thalassaemia del-3.7 Kb. SCD and G6PD deficiency genotypes were established. Prevalence of SCD in population at risk was 1/475 newborns. Prevalence of G6PD deficiency in population at risk was 1/43, and in autochthonous population was 1/527 newborns. In all the cases, sickle hemoglobin was confirmed by ARMS (amplification refractory mutation system). Association between betaS gene and alpha thalassaemia del-3.7 Kb was found in 32.2% of the samples, and an association between betaS gene and G6PD deficiency was observed in 7% of the samples. This study confirms the high prevalence of SCD and G6PD deficiency in population at risk as well as their genetic and clinical heterogeneity. The study of genotype/phenotype relationships allows a better knowledge of molecular mechanism and is useful to establish suitable criteria of diagnosis.

  13. Antibody deficiency in patients with frequent exacerbations of Chronic Obstructive Pulmonary Disease (COPD).

    Science.gov (United States)

    McCullagh, Brian N; Comellas, Alejandro P; Ballas, Zuhair K; Newell, John D; Zimmerman, M Bridget; Azar, Antoine E

    2017-01-01

    Chronic Obstructive Pulmonary Disease is the third leading cause of death in the US, and is associated with periodic exacerbations, which account for the largest proportion of health care utilization, and lead to significant morbidity, mortality, and worsening lung function. A subset of patients with COPD have frequent exacerbations, occurring 2 or more times per year. Despite many interventions to reduce COPD exacerbations, there is a significant lack of knowledge in regards to their mechanisms and predisposing factors. We describe here an important observation that defines antibody deficiency as a potential risk factor for frequent COPD exacerbations. We report a case series of patients who have frequent COPD exacerbations, and who were found to have an underlying primary antibody deficiency syndrome. We also report on the outcome of COPD exacerbations following treatment in a subset with of these patients with antibody deficiency. We identified patients with COPD who had 2 or more moderate to severe exacerbations per year; immune evaluation including serum immunoglobulin levels and pneumococcal IgG titers was performed. Patients diagnosed with an antibody deficiency syndrome were treated with either immunoglobulin replacement therapy or prophylactic antibiotics, and their COPD exacerbations were monitored over time. A total of 42 patients were identified who had 2 or more moderate to severe COPD exacerbations per year. Twenty-nine patients had an underlying antibody deficiency syndrome: common variable immunodeficiency (8), specific antibody deficiency (20), and selective IgA deficiency (1). Twenty-two patients had a follow-up for at least 1 year after treatment of their antibody deficiency, which resulted in a significant reduction of COPD exacerbations, courses of oral corticosteroid use and cumulative annual dose of oral corticosteroid use, rescue antibiotic use, and hospitalizations for COPD exacerbations. This case series identifies antibody deficiency as a

  14. Auditory post-processing in a passive listening task is deficient in Alzheimer's disease.

    Science.gov (United States)

    Bender, Stephan; Bluschke, Annet; Dippel, Gabriel; Rupp, André; Weisbrod, Matthias; Thomas, Christine

    2014-01-01

    To investigate whether automatic auditory post-processing is deficient in patients with Alzheimer's disease and is related to sensory gating. Event-related potentials were recorded during a passive listening task to examine the automatic transient storage of auditory information (short click pairs). Patients with Alzheimer's disease were compared to a healthy age-matched control group. A young healthy control group was included to assess effects of physiological aging. A bilateral frontal negativity in combination with deep temporal positivity occurring 500 ms after stimulus offset was reduced in patients with Alzheimer's disease, but was unaffected by physiological aging. Its amplitude correlated with short-term memory capacity, but was independent of sensory gating in healthy elderly controls. Source analysis revealed a dipole pair in the anterior temporal lobes. Results suggest that auditory post-processing is deficient in Alzheimer's disease, but is not typically related to sensory gating. The deficit could neither be explained by physiological aging nor by problems in earlier stages of auditory perception. Correlations with short-term memory capacity and executive control tasks suggested an association with memory encoding and/or overall cognitive control deficits. An auditory late negative wave could represent a marker of auditory working memory encoding deficits in Alzheimer's disease. Copyright © 2013 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  15. Prevalence of Celiac Disease in Patients with Iron Deficiency Anemia - a Systematic Review with Meta-analysis.

    Science.gov (United States)

    Mahadev, Srihari; Laszkowska, Monika; Sundström, Johan; Björkholm, Magnus; Lebwohl, Benjamin; Green, Peter Hr; Ludvigsson, Jonas F

    2018-04-21

    Anemia is common in patients with celiac disease and a frequent presentation. Guidelines recommend screening iron-deficient patients with anemia for celiac disease. However, the reported prevalence of celiac disease among patients with iron-deficiency anemia (IDA) varies. We performed a systematic review to determine the prevalence of biopsy-verified celiac disease in patients with IDA. We performed a systematic review of manuscripts published in PubMed Medline or EMBASE through July 2017 for the term celiac disease combined with anemia or iron-deficiency. We used fixed-effects inverse variance-weighted models to measure the pooled prevalence of celiac disease. Meta-regression was used to assess subgroup heterogeneity. We identified 18 studies comprising 2998 patients with IDA for inclusion in our analysis. Studies originated from the United Kingdom, United States, Italy, Turkey, Iran, and Israel. The crude unweighted prevalence of celiac disease was 4.8% (n=143). Using a weighted pooled analysis, we demonstrated a prevalence of biopsy-confirmed celiac disease 3.2% (95% CI, 2.6%-3.9%) in patients with IDA. However, heterogeneity was high (I 2 = 67.7%). The prevalence of celiac disease was not significantly higher in studies with a mean participant age older or younger than years, nor in studies with a mixed-sex vs female-predominant (≥60%) population. On meta-regression, year of publication, the proportion of females, age at celiac disease testing, and the prevalence of in the general population were not associated with the prevalence of celiac disease in patients with IDA. In the 8 studies fulfilling all our quality criteria, the pooled prevalence of celiac disease was 5.5% (95% CI, 4.1%-6.9%). In a systematic review and meta-analysis, we found that approximately 1 in 31 patients with IDA have histologic evidence of celiac disease. This prevalence value justifies the practice of testing patients with IDA for celiac disease. Copyright © 2018 AGA Institute

  16. 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)....

  17. Proximal Limb Weakness in a Patient with Celiac Disease: Copper Deficiency, Gluten Sensitivity, or Both as the Underlying Cause?

    Directory of Open Access Journals (Sweden)

    J. David Avila

    2016-01-01

    Full Text Available Celiac disease has been associated with several neurologic disorders which may result from micronutrient deficiencies, coexisting autoimmune conditions, or gluten sensitivity. Copper deficiency can produce multiple neurologic manifestations. Myeloneuropathy is the most common neurologic syndrome and it is often irreversible, despite copper replacement. We report the case of a 55-year-old man who presented with progressive proximal limb weakness and weight loss in the setting of untreated celiac disease without gastrointestinal symptoms. He had anemia, neutropenia, and severe hypocupremia. The pattern of weakness raised the suspicion that there was an underlying myopathy, although this was not confirmed by electrodiagnostic studies. Weakness and hematologic abnormalities resolved completely within 1 month of total parenteral nutrition with copper supplementation and a gluten-free diet. Myopathy can rarely occur in patients with celiac disease, but the mechanism is unclear. Pure proximal limb weakness has not been previously reported in copper deficiency. We propose that this may represent a novel manifestation of hypocupremia and recommend considering copper deficiency and gluten sensitivity in patients presenting with proximal limb weakness.

  18. 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 ...

  19. High Prevalence but Insufficient Treatment of Iron-Deficiency Anemia in Patients with Inflammatory Bowel Disease: Results of a Population-Based Cohort

    Science.gov (United States)

    Ott, Claudia; Liebold, Anne; Takses, Angela; Strauch, Ulrike G.; Obermeier, Florian

    2012-01-01

    Background. Iron-deficiency anemia is described to be a common problem in patients with inflammatory bowel disease (IBD), which is frequently associated with a reduced quality of life. Therefore, the aim of this study is to assess the prevalence of iron deficiency anemia in a population-based cohort at time of first diagnosis and during the early course of the disease. Methods. As far as available, lab values of patients registered in the population-based “Oberpfalz cohort” were screened. In anemic patients, we further investigated all laboratory results to differentiate between iron deficiency and other reasons for anemia. All patients with any kind of anemia were interviewed separately according to symptoms of iron-deficiency anemia and administration of iron. Results. In total, we evaluated hemoglobin values of 279 patients (183 Crohn's disease, 90 ulcerative colitis, and 6 indeterminate colitis). Lab data which allowed further differentiation of the type of anemia were available in 70% of anemic patients, in 34.4% values of iron, ferritin and transferrin saturation had been measured. At time of first diagnosis, an iron-deficiency anemia was diagnosed in 26 of 68 patients with anemia (38.2%, 20 CD, 4 UC, and 2 IC patients), but only 9 patients (34.6%) received subsequent iron therapy. After one year, 27 patients were identified to have an iron-deficiency anemia (19 CD, 8 UC), 20 of them were treated with iron (71.4%). Of 9 patients with proven iron-deficiency anemia at time of first diagnosis and subsequent administration of iron, 5 (55.5%) had iron-deficiency anemia despite permanent treatment after one year. In total, 38 patients (54.3%) did not receive any iron substitution at all despite of proven iron-deficiency anemia, and only 13 patients of 74 patients were treated with intravenous iron (17.6%). Conclusion. We found a high prevalence of iron-deficiency anemia at different points during the early course of disease in this population-based cohort of

  20. Association between vitamin D deficiency and anemia in inflammatory bowel disease patients with ileostomy

    Directory of Open Access Journals (Sweden)

    Andre Fialho

    2015-07-01

    Full Text Available Background: Vitamin D deficiency is commonly seen in patients with inflammatory bowel disease (IBD. Vitamin D deficiency in IBD patients with ileostomy has not been systemically studied. The aim of the study was to assess the frequency and risk factors associated with low 25(OH D3 levels in those patients. Methods: 112 eligible IBD patients with ileostomy were studied. Demographic, clinical, and endoscopic variables were analyzed. Vitamin D levels before and after ileostomy were compared when available. Levels of serum 25(OHD3 <20 ng/mL were classed as being deficient. Results: 112 eligible ileostomy patients were included. The mean vitamin D level was 21.47 ± 1.08 ng/dl. Low levels of vitamin D (<30 ng/dl were present in 92 patients (82%. Vitamin D deficiency (<20 ng/dL was seen in 55 patients (49%. There was no difference between patients with or without vitamin D deficiency regarding demographic variables, medication use and duration of ileostomy. Neo-ileal inflammation on endoscopy was not associated with vitamin D deficiency (p = 0.155. Lower levels of phosphorus (p = 0.020 or hemoglobin (p = 0.019 and shorter duration of IBD (p = 0.047 were found in patients with vitamin D deficiency. In multivariate analysis, lower levels of phosphorus (odds ratio [OR]: 1.83, 95% confidence interval [CI]: 1.16–2.89, p = 0.009 and hemoglobin (OR: 1.32, 95% CI: 1.08–1.60, p = 0.006 remained significantly associated with vitamin D deficiency. Conclusion: Vitamin D deficiency is common in IBD patients with ileostomy and is associated with low hemoglobin levels. Further studies are needed to evaluate vitamin D supplementation as a possible adjuvant in the treatment of anemia of chronic disease in IBD patients. Resumo: Introdução: A deficiência de vitamina D em pacientes com doença inflamatória intestinal submetidos a ileostomia não foi estudada sistematicamente. O objetivo desse estudo foi avaliar a frequência e os fatores de

  1. Oxidative stress and dopamine deficiency in a genetic mouse model of Lesch-Nyhan disease.

    NARCIS (Netherlands)

    Visser, J.E.; Smith, D.W.; Moy, S.S.; Breese, G.R.; Friedmann, T.; Rothstein, J.D.; Jinnah, H.A.

    2002-01-01

    Lesch-Nyhan disease, a neurogenetic disorder caused by congenital deficiency of the purine salvage enzyme hypoxanthine guanine phosphoribosyl transferase, is associated with a prominent loss of striatal dopamine. The current studies address the hypothesis that oxidant stress causes damage or

  2. [Prevalence and characteristics of anemia and iron deficiency in patients hospitalized for gastrointestinal diseases in Spain].

    Science.gov (United States)

    Mearin, Fermín; Barreiro-de Acosta, Manuel; González-Galilea, Ángel; Gisbert, Javier P; Cucala, Mercedes; Ponce, Julio

    2013-10-01

    To determine the prevalence and characteristics of anemia and iron deficiency in patients hospitalized for gastrointestinal diseases. An epidemiological, multicenter, mixed design study (retrospective review of randomized clinical records and prospective visits) conducted between February 2010 and March 2011 in 22 Spanish gastroenterology departments. Severe anemia was defined as Hb iron deficiency as ferritin anemia at admission was 60% (95% CI 55 to 65), and anemia was severe (Hb iron deficiency was 54% of evaluable patients (95% CI 47 to 61). Gastrointestinal bleeding at admission was found in 39% of the patients, of whom 83% (121/146) were anemic. At discharge, the proportion of anemic patients was unchanged (from 60% at admission to 58% at discharge) (95% CI 53 to 63) and iron deficiency was found in 41% (95% CI 32 to 50): anemia was severe in 17% and mild/moderate in 41%. During follow-up, at 3-6 months after admission, 44% (95% CI 39 to 50) of evaluable patients continued to have iron deficiency and 28% (95% CI 23 to 32) were still anemic: 5% severe and 23% mild/moderate. The prevalence of iron deficiency was 44% (95% CI: 39-50). During admission, 50% of patients with anemia did not receive treatment. At discharge, 55% were untreated. The prevalence of anemia in patients hospitalized for gastroenterological diseases was very high. Anemia persisted in over a quarter of patients at the follow-up visit. Only half of hospitalized patients received treatment for anemia, even when the anemia was severe. Copyright © 2013 Elsevier España, S.L. y AEEH y AEG. All rights reserved.

  3. Spectrum of SMPD1 mutations in Asian-Indian patients with acid sphingomyelinase (ASM)-deficient Niemann-Pick disease.

    Science.gov (United States)

    Ranganath, Prajnya; Matta, Divya; Bhavani, Gandham SriLakshmi; Wangnekar, Savita; Jain, Jamal Mohammed Nurul; Verma, Ishwar C; Kabra, Madhulika; Puri, Ratna Dua; Danda, Sumita; Gupta, Neerja; Girisha, Katta M; Sankar, Vaikom H; Patil, Siddaramappa J; Ramadevi, Akella Radha; Bhat, Meenakshi; Gowrishankar, Kalpana; Mandal, Kausik; Aggarwal, Shagun; Tamhankar, Parag Mohan; Tilak, Preetha; Phadke, Shubha R; Dalal, Ashwin

    2016-10-01

    Acid sphingomyelinase (ASM)-deficient Niemann-Pick disease is an autosomal recessive lysosomal storage disorder caused by biallelic mutations in the SMPD1 gene. To date, around 185 mutations have been reported in patients with ASM-deficient NPD world-wide, but the mutation spectrum of this disease in India has not yet been reported. The aim of this study was to ascertain the mutation profile in Indian patients with ASM-deficient NPD. We sequenced SMPD1 in 60 unrelated families affected with ASM-deficient NPD. A total of 45 distinct pathogenic sequence variants were found, of which 14 were known and 31 were novel. The variants included 30 missense, 4 nonsense, and 9 frameshift (7 single base deletions and 2 single base insertions) mutations, 1 indel, and 1 intronic duplication. The pathogenicity of the novel mutations was inferred with the help of the mutation prediction software MutationTaster, SIFT, Polyphen-2, PROVEAN, and HANSA. The effects of the identified sequence variants on the protein structure were studied using the structure modeled with the help of the SWISS-MODEL workspace program. The p. (Arg542*) (c.1624C>T) mutation was the most commonly identified mutation, found in 22% (26 out of 120) of the alleles tested, but haplotype analysis for this mutation did not identify a founder effect for the Indian population. To the best of our knowledge, this is the largest study on mutation analysis of patients with ASM-deficient Niemann-Pick disease reported in literature and also the first study on the SMPD1 gene mutation spectrum in India. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  4. 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 ...

  5. Wolman's disease and cholesteryl ester storage disorder: the phenotypic spectrum of lysosomal acid lipase deficiency.

    Science.gov (United States)

    Pericleous, Marinos; Kelly, Claire; Wang, Tim; Livingstone, Callum; Ala, Aftab

    2017-09-01

    Lysosomal acid lipase deficiency is a rare, autosomal recessive condition caused by mutations in the gene encoding lysosomal acid lipase (LIPA) that result in reduced or absent activity of this essential enzyme. The severity of the resulting disease depends on the nature of the underlying mutation and magnitude of its effect on enzymatic function. Wolman's disease is a severe disorder that presents during infancy, resulting in failure to thrive, hepatomegaly, and hepatic failure, and an average life expectancy of less than 4 months. Cholesteryl ester storage disorder arises later in life and is less severe, although the two diseases share many common features, including dyslipidaemia and transaminitis. The prevalence of these diseases has been estimated at one in 40 000 to 300 000, but many cases are undiagnosed and unreported, and awareness among clinicians is low. Lysosomal acid lipase deficiency-which can be diagnosed using dry blood spot testing-is often misdiagnosed as non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), hereditary dyslipidaemia, or cryptogenic cirrhosis. There are no formal guidelines for treatment of these patients, and treatment options are limited. In this Review we appraise the existing literature on Wolman's disease and cholesteryl ester storage disease, and discuss available treatments, including enzyme replacement therapy, oral lipid-lowering therapy, stem-cell transplantation, and liver transplantation. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Lycopene Deficiency in Ageing and Cardiovascular Disease

    Science.gov (United States)

    Petyaev, Ivan M.

    2016-01-01

    Lycopene is a hydrocarbon phytochemical belonging to the tetraterpene carotenoid family and is found in red fruit and vegetables. Eleven conjugated double bonds predetermine the antioxidant properties of lycopene and its ability to scavenge lipid peroxyl radicals, reactive oxygen species, and nitric oxide. Lycopene has a low bioavailability rate and appears in the blood circulation incorporated into chylomicrons and other apo-B containing lipoproteins. The recent body of evidence suggests that plasma concentration of lycopene is not only a function of intestinal absorption rate but also lycopene breakdown via enzymatic and oxidative pathways in blood and tissues. Oxidative stress and the accumulation of reactive oxygen species and nitric oxide may represent a major cause of lycopene depletion in ageing, cardiovascular disease, and type 2 diabetes mellitus. It has been shown recently that low carotenoid levels, and especially decreased serum lycopene levels, are strongly predictive of all-cause mortality and poor outcomes of cardiovascular disease. However, there is a poor statistical association between dietary and serum lycopene levels which occurs due to limited bioavailability of lycopene from dietary sources. Hence, it is very unlikely that nutritional intervention alone could be instrumental in the correction of lycopene and carotenoid deficiency. Therefore, new nutraceutical formulations of carotenoids with enhanced bioavailability are urgently needed. PMID:26881023

  7. Vitamin D deficiency: infertility and neurodevelopmental diseases (attention deficit hyperactivity disorder, autism, and schizophrenia).

    Science.gov (United States)

    Berridge, Michael J

    2018-02-01

    The process of development depends on a number of signaling systems that regulates the progressive sequence of developmental events. Infertility and neurodevelopmental diseases, such as attention deficit hyperactivity disorder, autism spectrum disorders, and schizophrenia, are caused by specific alterations in these signaling processes. Calcium signaling plays a prominent role throughout development beginning at fertilization and continuing through early development, implantation, and organ differentiation such as heart and brain development. Vitamin D plays a major role in regulating these signaling processes that control development. There is an increase in infertility and an onset of neurodevelopmental diseases when vitamin D is deficient. The way in which vitamin D deficiency acts to alter development is a major feature of this review. One of the primary functions of vitamin D is to maintain the phenotypic stability of both the Ca 2+ and redox signaling pathways that play such a key role throughout development.

  8. Risk Factors for Vitamin D Deficiency and Impact of Repletion in a Tertiary Care Inflammatory Bowel Disease Population.

    Science.gov (United States)

    Zullow, Samantha; Jambaulikar, Guruprasad; Rustgi, Ankur; Quezada, Sandra; Cross, Raymond K

    2017-08-01

    Many patients with inflammatory bowel disease (IBD) are vitamin D deficient. The purpose of our study was to identify risk factors for vitamin D deficiency in IBD and to assess the impact of vitamin D repletion on disease activity and quality of life (QOL). Patients with at least one 25-OH vitamin D level measured between 2004 and 2011 were included. Patients with a level vitamin D level of ≥30, 20-29, and vitamin D vitamin D level vitamin D levels. Non-Caucasian race and female gender are associated with low vitamin D. UC was associated with lower risk of vitamin D insufficiency. In CD, vitamin D repletion is associated with decreased disease activity and increased QOL.

  9. 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.

  10. ASSOCIATION OF POTENTIAL CELIAC DISEASE AND REFRACTORY IRON DEFICIENCY ANEMIA IN CHILDREN AND ADOLESCENTS.

    Science.gov (United States)

    Shahriari, Mahdi; Honar, Naser; Yousefi, Ali; Javaherizadeh, Hazhir

    2018-01-01

    Celiac disease is an enteropathy caused by dietary gluten. The combination of serologic, genetic and histologic data has led to description of other categories of this disease. There are a number of patients with iron deficiency anemia (IDA) that do not respond to iron treatment and may be repeated for many times, Therefore, we aimed to investigate celiac disease in this group. In this cross sectional transverse prospective study from August 2011 to February 2013, in a Pediatric care clinic affiliated to Shiraz University of Medical Sciences, 184 children including 92 IDA patients who responded to treatment using iron supplement, 45 non-responding iron deficient patients, and 47 healthy individuals, with the maximum age of 18 years, with written consent from their parents, participated in serologic screening (with Anti-TTG antibody and anti-Endomysial antibody) for celiac disease. Patients with at least one positive serology test underwent multiple mucosal biopsy from bulb and duodenum. Among 184 participants, 19 (10.3%) subjects had positive serologic test for celiac disease, including 13 (28.9%) patients in the group with refractory IDA, 5 (5.4%) patients in the group with treated IDA, and 1 patient in the healthy group. The frequency of positive serologic test in the group with IDA resistant to treatment was prominently higher than the other two groups (Pceliac test who underwent endoscopy and biopsy, no histologic evidence of celiac disease was seen. They were diagnosed as potential celiac disease. Frequency of potential celiac disease in patients with refractory IDA was higher than control the subjects. Therefore, we recommend serologic screening for early detection and minimizing the complications of celiac disease and repeated iron therapy for this group.

  11. A case presenting concurrence of Marfan syndrome, Basedow's disease and Arg353Gln polymorphism-related factor VII deficiency.

    Science.gov (United States)

    Tanaka, Kotoko; Seino, Yoshihiko; Inokuchi, Koiti; Ohmura, Kazuko; Kobayashi, Yoshinori; Takano, Teruo

    2005-02-15

    We report the case of a 48-year-old Japanese man who suffered from Marfan syndrome with severe aortic regurgitation, mitral regurgitation and rapid atrial fibrillation, which were aggravated by hyperdynamic circulatory conditions associated with coexistent Basedow's disease. Furthermore, concurrence of Arg353Gln polymorphism-related factor VII deficiency was discovered at the preoperative assessments. Both of his two brothers suffered from Marfan syndrome; however they had no findings of Arg353Glu polymorphism-related factor VII deficiency or Basedow's disease. After normalization of thyroid function, he had successfully the operations of Bentall procedure: a composite prosthetic graft: replacement of both the ascending aorta and aortic valve, and mitral valve annuloplasty. No specific therapy such as fresh frozen plasma or factor VII replacement therapy was required. He completely returned to his business work 6 weeks after the operation. Concurrence of Marfan syndrome and factor VII deficiency induced by two-hit genomic abnormalities and furthermore Basedow's disease, which significantly compromised the pathophysiological condition of Marfan syndrome, is extremely rare.

  12. Bones and Crohn's: Estradiol deficiency in men with Crohn's disease is not associated with reduced bone mineral density

    Directory of Open Access Journals (Sweden)

    Boehm BO

    2008-10-01

    Full Text Available Abstract Background Reduced bone mineral density (BMD and osteoporosis are frequent in Crohn's disease (CD, but the underlying mechanisms are still not fully understood. Deficiency of sex steroids, especially estradiol (E2, is an established risk factor in postmenopausal osteoporosis. Aim To assess if hormonal deficiencies in male CD patients are frequent we investigated both, sex steroids, bone density and bone metabolism markers. Methods 111 male CD patients underwent osteodensitometry (DXA of the spine (L1–L4. Disease related data were recorded. Disease activity was estimated using Crohn's disease activity index (CDAI. Testosterone (T, dihydrotestosterone (DHT, estradiol (E2, sex hormone binding globulin (SHBG, Osteocalcin and carboxyterminal cross-linked telopeptids (ICTP were measured in 111 patients and 99 age-matched controls. Results Patients had lower T, E2 and SHBG serum levels (p 10 g had lower BMD. 32 (28.8% patients showed osteoporosis, 55 (49.5% osteopenia and 24 (21.6% had normal BMD. Patients with normal or decreased BMD showed no significant difference in their hormonal status. No correlation between markers of bone turnover and sex steroids could be found. ICTP was increased in CD patients (p Conclusion We found an altered hormonal status – i.e. E2 and, to a lesser extent T deficiency – in male CD patients but failed to show an association to bone density or markers of bone turnover. The role of E2 in the negative skeletal balance in males with CD, analogous to E2 deficiency in postmenopausal females, deserves further attention.

  13. Coupling fibroblast growth factor 23 production and cleavage: iron deficiency, rickets, and kidney disease.

    Science.gov (United States)

    Wolf, Myles; White, Kenneth E

    2014-07-01

    High levels of fibroblast growth factor 23 (FGF23) cause the rare disorders of hypophosphatemic rickets and are a risk factor for cardiovascular disease and death in patients with chronic kidney disease (CKD). Despite major advances in understanding FGF23 biology, fundamental aspects of FGF23 regulation in health and in CKD remain mostly unknown. Autosomal dominant hypophosphatemic rickets (ADHR) is caused by gain-of-function mutations in FGF23 that prevent its proteolytic cleavage, but affected individuals experience a waxing and waning course of phosphate wasting. This led to the discovery that iron deficiency is an environmental trigger that stimulates FGF23 expression and hypophosphatemia in ADHR. Unlike osteocytes in ADHR, normal osteocytes couple increased FGF23 production with commensurately increased FGF23 cleavage to ensure that normal phosphate homeostasis is maintained in the event of iron deficiency. Simultaneous measurement of FGF23 by intact and C-terminal assays supported these breakthroughs by providing minimally invasive insight into FGF23 production and cleavage in bone. These findings also suggest a novel mechanism of FGF23 elevation in patients with CKD, who are often iron deficient and demonstrate increased FGF23 production and decreased FGF23 cleavage, consistent with an acquired state that mimics the molecular pathophysiology of ADHR. Iron deficiency stimulates FGF23 production, but normal osteocytes couple increased FGF23 production with increased cleavage to maintain normal circulating levels of biologically active hormone. These findings uncover a second level of FGF23 regulation within osteocytes, failure of which culminates in elevated levels of biologically active FGF23 in ADHR and perhaps CKD.

  14. Diagnóstico diferencial da deficiência de ferro Differential diagnosis of iron deficiency

    Directory of Open Access Journals (Sweden)

    Perla Vicari

    2010-06-01

    Full Text Available A deficiência de ferro é considerada a patologia hematológica mais prevalente no homem. Assim, é fundamental a adequada identificação de suas causas, bem como a diferenciação com outras patologias distintas para adequada abordagem da deficiência de ferro. Neste artigo são brevemente descritas outras condições que podem cursar com anemia microcítica, tais como: talassemias, anemia de doença crônica, anemia sideroblástica e envenenamento por chumbo, patologias estas que devem ser afastadas durante investigação de anemia ferropriva.Iron deficiency is considered to be the commonest hematological pathology in humans. Thus, the essential steps in an adequate approach of iron deficiency include: the proper identification of its causes and the differentiation between iron deficiency and other conditions. This article briefly describes other conditions that may present with microcytic anemia such as thalassemia, anemia of chronic diseases, sideroblastic anemia and lead intoxication. These diseases should be considered during the investigation of iron deficiency anemia.

  15. Vitamin D insufficiency and deficiency in mexican patients with systemic lupus erythematosus: Prevalence and relationship with disease activity.

    Science.gov (United States)

    García-Carrasco, Mario; Mendoza-Pinto, Claudia; Etchegaray-Morales, Ivet; Soto-Santillán, Pamela; Jiménez-Herrera, Erick Alejandro; Robles-Sánchez, Viridiana; Rodríguez-Gallegos, Alma; Ramos-Varela, Araceli; Muñoz-Guarneros, Margarita; Ruiz-Argüelles, Alejandro

    To determine and compare the prevalence of vitamin D insufficiency and deficiency in patients with systemic lupus erythematosus (SLE) with and without disease activity. We made a comparative, observational, cross-sectional, prospective study of 137 women with SLE according to American College of Rheumatology criteria. Patients with chronic kidney disease, cancer, hyperparathyroidism, pregnancy, and lactation were excluded. Disease activity was assessed using the MEX-SLEDAI score: a score of ≥3 was considered as disease activity. Data were collected on diabetes mellitus, the use of corticosteroids, chloroquine, and immunosuppressants, photoprotection and vitamin D supplementation. Vitamin D levels were measured by chemiluminescent immunoassay: insufficiency was defined as serum 25-hydroxyvitamin D <30ng/ml and deficiency as <10ng/ml. 137 women with SLE (mean age 45.9±11.6 years, disease duration 7.7±3.4 years) were evaluated. Mean disease activity was 2 (0-8): 106 patients had no disease activity and 31 had active disease (77.4% versus 22.6%). Vitamin D insufficiency and deficiency was found in 122(89.0%) and 4 (2.9%) patients, respectively. There was no significant difference in vitamin D levels between patients with and without active disease (19.3±4.5 versus 19.7±6.8; P=.75). No correlation between the MEX-SLEDAI score (P=.21), photosensitivity, photoprotection, prednisone or chloroquine use and vitamin D supplementation was found. Women with SLE had a high prevalence of vitamin D insufficient. No association between vitamin D levels and disease activity was found. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

  16. 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 ...

  17. Temporal gene expression profiling reveals CEBPD as a candidate regulator of brain disease in prosaposin deficient mice

    Directory of Open Access Journals (Sweden)

    Ran Huimin

    2008-08-01

    Full Text Available Abstract Background Prosaposin encodes, in tandem, four small acidic activator proteins (saposins with specificities for glycosphingolipid (GSL hydrolases in lysosomes. Extensive GSL storage occurs in various central nervous system regions in mammalian prosaposin deficiencies. Results Our hypomorphic prosaposin deficient mouse, PS-NA, exhibited 45% WT levels of brain saposins and showed neuropathology that included neuronal GSL storage and Purkinje cell loss. Impairment of neuronal function was observed as early as 6 wks as demonstrated by the narrow bridges tests. Temporal transcriptome microarray analyses of brain tissues were conducted with mRNA from three prosaposin deficient mouse models: PS-NA, prosaposin null (PS-/- and a V394L/V394L glucocerebrosidase mutation combined with PS-NA (4L/PS-NA. Gene expression alterations in cerebrum and cerebellum were detectable at birth preceding the neuronal deficits. Differentially expressed genes encompassed a broad spectrum of cellular functions. The number of down-regulated genes was constant, but up-regulated gene numbers increased with age. CCAAT/enhancer-binding protein delta (CEBPD was the only up-regulated transcription factor in these two brain regions of all three models. Network analyses revealed that CEBPD has functional relationships with genes in transcription, pro-inflammation, cell death, binding, myelin and transport. Conclusion These results show that: 1 Regionally specific gene expression abnormalities precede the brain histological and neuronal function changes, 2 Temporal gene expression profiles provide insights into the molecular mechanism during the GSL storage disease course, and 3 CEBPD is a candidate regulator of brain disease in prosaposin deficiency to participate in modulating disease acceleration or progression.

  18. [Analysis in pulmonary ventilatory function from 100 patients with ano-rectal diseases caused by deficiency of qi].

    Science.gov (United States)

    Wang, W

    1999-03-01

    To explore the pathogenesis of ano-rectal diseases caused by deficiency of Qi, which is correlated with obstruction of pulmonary ventilation. The pulmonary ventilatory function was measured in 100 patients with the internal piles, the interno-external hemorrhoid and prolapse of rectum, the prolapse of anus was the principal symptom of them. Data from the 100 patients showed that 67% of them were diagnosed with the obstruction of pulmonary ventilation, the ratio was far less in the health control group. FEV 1.0 (mean +/- s) (2011.65 +/- 875) ml, MMF (1.84 +/- 1.24) L/s and PEF (2.34 +/- 1.51) L/s in male patients, (1551.54 +/- 514) ml, (1.57 +/- 0.62) L/s and (1.85 +/- 0.92) L/s in female patients, but those values were higher in the control than in the patients. The statistical analysis was performed and the difference was significant between patients and the control group (P < 0.01). The patients with ano-rectal diseases caused by deficiency of Qi accompanied with obstruction of pulmonary ventilation in different degree and varied sorts, it confirmed that the pathogenesis of ano-rectal diseases caused by deficiency of Qi is related with "sinking of pectoral Qi".

  19. Iron-Deficiency Anemia

    Medline Plus

    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 ...

  20. The HRCT appearances of granulomatous pulmonary disease in common variable immune deficiency

    International Nuclear Information System (INIS)

    Park, J.E.S.; Beal, I.; Dilworth, J.P.; Tormey, V.; Haddock, J.

    2005-01-01

    Approximately 10% of patients with common variable immune deficiency have systemic granulomatous disease with associated interstitial lung disease. From a population of patients with CVID attending a large tertiary referral clinic for primary immunodeficiency diseases we selected a cohort who had a restrictive defect or impaired gas transfer on pulmonary function testing and/or histologically proven granulomatous disease. HRCT scans of the thorax were reviewed retrospectively in 18 patients by two radiologists. Thirteen patients had diffuse reticulation, which varied from fine to coarse with features of fibrosis. Nodules were found in eight patients. In seven, these were associated with reticulation and in one they were an isolated finding. Bronchiectasis was found as the only abnormality in three and in addition to diffuse reticulation or nodules in another three patients. Greater appreciation of the spectrum of the radiological abnormalities in CVID patients with interstitial lung disease is important. Deteriorating lung function in patients with granulomatous CVID may be secondary to interstitial lung disease rather than bronchiectasis, and treatment should be tailored accordingly

  1. The HRCT appearances of granulomatous pulmonary disease in common variable immune deficiency

    Energy Technology Data Exchange (ETDEWEB)

    Park, J.E.S. [Royal Free and Hampstead NHS Trust, Pond Street, London NW3 2QG (United Kingdom); Beal, I. [Royal Free and Hampstead NHS Trust, Pond Street, London NW3 2QG (United Kingdom); Dilworth, J.P. [Royal Free and Hampstead NHS Trust, Pond Street, London NW3 2QG (United Kingdom); Tormey, V. [Royal Free and Hampstead NHS Trust, Pond Street, London NW3 2QG (United Kingdom); Haddock, J. [Royal Free and Hampstead NHS Trust, Pond Street, London NW3 2QG (United Kingdom)]. E-mail: jamandahaddock@royalfree.nhs.uk

    2005-06-01

    Approximately 10% of patients with common variable immune deficiency have systemic granulomatous disease with associated interstitial lung disease. From a population of patients with CVID attending a large tertiary referral clinic for primary immunodeficiency diseases we selected a cohort who had a restrictive defect or impaired gas transfer on pulmonary function testing and/or histologically proven granulomatous disease. HRCT scans of the thorax were reviewed retrospectively in 18 patients by two radiologists. Thirteen patients had diffuse reticulation, which varied from fine to coarse with features of fibrosis. Nodules were found in eight patients. In seven, these were associated with reticulation and in one they were an isolated finding. Bronchiectasis was found as the only abnormality in three and in addition to diffuse reticulation or nodules in another three patients. Greater appreciation of the spectrum of the radiological abnormalities in CVID patients with interstitial lung disease is important. Deteriorating lung function in patients with granulomatous CVID may be secondary to interstitial lung disease rather than bronchiectasis, and treatment should be tailored accordingly.

  2. Acid sphingomyelinase (Asm) deficiency patients in The Netherlands and Belgium: disease spectrum and natural course in attenuated patients.

    Science.gov (United States)

    Hollak, C E M; de Sonnaville, E S V; Cassiman, D; Linthorst, G E; Groener, J E; Morava, E; Wevers, R A; Mannens, M; Aerts, J M F G; Meersseman, W; Akkerman, E; Niezen-Koning, K E; Mulder, M F; Visser, G; Wijburg, F A; Lefeber, D; Poorthuis, B J H M

    2012-11-01

    Niemann-Pick disease (NPD) is a neurovisceral lysosomal storage disorder caused by acid sphingomyelinase (ASM) deficiency, which can be categorized as either Niemann-Pick disease type A [NPD-A], with progressive neurological disease and death in early childhood, or as Niemann-Pick disease type B [NPD-B], with a more variable spectrum of manifestations. Enzyme replacement therapy (ERT) with recombinant sphingomyelinase is currently studied as potential treatment for NPD-B patients. The objective of this study is to characterize the clinical features of patients with ASM deficiency in the Netherlands and Belgium with focus on the natural disease course of NPD-B patients. Prospective and retrospective data on ASM deficient patients were collected in The Netherlands and part of Belgium. Patients with NPD-B that could be followed prospectively were evaluated every 6-12 months for pulmonary function tests, 6 minute walk test (6 MWT), imaging (bone marrow infiltration measured by QCSI, organ volumes by MRI and CT scan of the lungs) and biochemical markers. Twenty-five patients with ASM deficiency were identified (13 males, 12 females, median age 13years, range 1-59 years). Nine patients had died at the time of the study, including four NPD-A patients at the age of 1,1, 2, 3 and five NPDB patents at the age of 5, 6, 43, 56 and 60 years. There was a high prevalence of homozygosity and compound heterozygosity for the common p.Arg608del mutation in 43% and 19% of NPD-B patients, respectively. In NPD-B patients, thrombocytopenia was present in most, while anemia and leucopenia were less common (33% and 6 % respectively). HDL cholesterol was reduced in most patients. Pulmonary disease was severe in several patients. Follow-up up to 11 years revealed a gradual decrease in platelet count. Detailed investigations in 6 NPD-B patients with follow-up in 4 patients revealed remarkable stable disease parameters up to 6 years, with some decline in pulmonary function and 6 MWT. Bone

  3. Managing iron deficiency and iron deficiency anemia in inflammatory bowel disease. The results of the "Gestiona hierro-EII" survey.

    Science.gov (United States)

    Casellas Jordá, Francesc; Vera Mendoza, Isabel; Barreiro-de Acosta, Manuel; Vázquez Morón, Juan María; López Román, Javier; Júdez Gutiérrez, Javier

    2018-03-01

    iron deficiency anemia is a common and very relevant manifestation of inflammatory bowel disease (IBD). Although clinical practice guidelines have been published and updated on this subject, the management in the daily practice of this complication is far from optimal. to determine the actual management, needs and limitations of anemia in IBD by means of a survey of gastroenterology specialists. a self-administered telematic survey was carried out between April and May 2017 and was sent to SEPD members. The survey included four sections: participant demographics, monitoring, treatment and limitations/needs. a total of 122 evaluable surveys were received from all Spanish autonomous communities. Iron deficiency anemia is considered as a frequent manifestation of IBD and is monitored in all patients via the measurement of hemoglobin and ferritin. In the case of anemia, the survey respondents found it necessary to rule out the presence of IBD activity. However, only 14.8% prescribed intravenous iron when IBD was active. The required dose of intravenous iron is mainly calculated according to patient needs but only 33.1% of clinicians infused doses of 1 g or more. the "Gestiona Hierro EII" survey on the management of anemia in IBD demonstrated a high quality of care, even though some aspects need to be improved. These included the prescription of intravenous iron for patients with disease activity, the use of high-dose intravenous iron and the implementation of algorithms into clinical practice.

  4. A rare case of Addison's disease, hepatitis, thyreoiditis, positive IgG anti-tissue transglutaminase antibodies and partial IgA deficiency.

    Science.gov (United States)

    Baleva, Marta P; Mihaylova, Snejina; Yankova, Petja; Atanasova, Iliana; Nikolova-Vlahova, Milena; Naumova, Elissaveta

    2016-01-01

    Selective IgA deficiency (IgAD) is the most prevalent type of primary immune deficiencies, but partial IgA deficiency is even more common. Addison's disease is a rare condition associated with primary adrenal insufficiency due to infection or autoimmune destruction of the adrenals. The association between IgA deficiency and Addison's disease is very rare. We observed a 22-year-old male patient with marked darkening of the skin, especially on the palms and areolae, jaundice on the skin and sclera, astheno-adynamia, hypotension (80/50 mm Hg), and pain in the right hypochondrium. The laboratory investigations revealed increased serum levels of total and indirect bilirubin, AST, ALT, GGT and LDH, negative HBsAg, anti-HBc IgM, anti-HCV and anti-HAV IgM, very low serum IgA levels (0.16 g/l) with normal IgG and IgM, negative ANA, ANCA, AMA, LKM-1, anti-GAD-60, anti-IA-2, anti-thyroglobulin antibodies, a mild increase in anti-TPO antibodies titer, a marked increase in IgG anti-tissue transglutaminase antibodies, with no typical changes in cellular immunity, negative T-SPOT-TB test, HLA - A*01; B*08; DRB1*03; DQB1*02, karyotype - 46, XY. We present a rare case of partial IgA deficiency with Addison's disease, hepatitis, thyroiditis and positive anti-tissue transglutaminase antibodies. IgAD and some autoimmune disorders share several predisposing HLA genes, thus explaining the increased prevalence of IgAD in certain patient groups.

  5. 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 ...

  6. Kawasaki disease with G6PD deficiency--report of one case and literature review.

    Science.gov (United States)

    Chen, Chia-Hao; Lin, Li-Yan; Yang, Kuender D; Hsieh, Kai-Sheng; Kuo, Ho-Chang

    2014-06-01

    Kawasaki disease (KD) is a systemic vasculitis primarily affecting children who are younger than 5 years. The most serious complications are coronary artery aneurysms and sequelae of vasculitis with the subsequent development of coronary artery aneurysm. According to the literature, intravenous immunoglobulin (IVIG) plus high-dose aspirin (acetylsalicylic acid) were standard treatment for KD, whereas low-dose aspirin (3-5 mg/kg/day) was used for thrombocytosis in KD via antiplatelet effect. However, aspirin has been reported to have hemolytic potential in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency. We report a child with G6PD-deficiency who has KD, and review the literature. Copyright © 2012. Published by Elsevier B.V.

  7. Liver and Skin Histopathology in Adults with Acid Sphingomyelinase Deficiency (Niemann-Pick Disease Type B)

    OpenAIRE

    Thurberg, Beth L.; Wasserstein, Melissa P.; Schiano, Thomas; O’Brien, Fanny; Richards, Susan; Cox, Gerald F.; McGovern, Margaret M.

    2012-01-01

    Acid sphingomyelinase deficiency (ASMD) is a lysosomal storage disorder characterized by the pathologic accumulation of sphingomyelin in multiple cells types, and occurs most prominently within the liver, spleen and lungs, leading to significant clinical disease. Seventeen ASMD patients underwent a liver biopsy during baseline screening for a Phase 1 trial of recombinant human acid sphingomyelinase (rhASM) in adults with Niemann-Pick disease type B. Eleven of the 17 were enrolled in the trial...

  8. 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 ...

  9. 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 ...

  10. Prevalence of high blood pressure, heart disease, thalassemia, sickle-cell anemia, and iron-deficiency anemia among the UAE adolescent population.

    Science.gov (United States)

    Barakat-Haddad, Caroline

    2013-01-01

    This study examined the prevalence of high blood pressure, heart disease, and medical diagnoses in relation to blood disorders, among 6,329 adolescent students (age 15 to 18 years) who reside in the United Arab Emirates (UAE). Findings indicated that the overall prevalence of high blood pressure and heart disease was 1.8% and 1.3%, respectively. Overall, the prevalence for thalassemia, sickle-cell anemia, and iron-deficiency anemia was 0.9%, 1.6%, and 5%, respectively. Bivariate analysis revealed statistically significant differences in the prevalence of high blood pressure among the local and expatriate adolescent population in the Emirate of Sharjah. Similarly, statistically significant differences in the prevalence of iron-deficiency anemia were observed among the local and expatriate population in Abu Dhabi city, the western region of Abu Dhabi, and Al-Ain. Multivariate analysis revealed the following significant predictors of high blood pressure: residing in proximity to industry, nonconventional substance abuse, and age when smoking or exposure to smoking began. Ethnicity was a significant predictor of heart disease, thalassemia, sickle-cell anemia, and iron-deficiency anemia. In addition, predictors of thalassemia included gender (female) and participating in physical activity. Participants diagnosed with sickle-cell anemia and iron-deficiency anemia were more likely to experience different physical activities.

  11. Comorbidity and cardiovascular risk factors in adult GH deficiency following treatment for Cushing's disease or non-functioning pituitary adenomas during childhood

    DEFF Research Database (Denmark)

    Ragnarsson, Oskar; Höybye, Charlotte; Jönsson, Peter J

    2012-01-01

    Cushing's disease (CD) and non-functioning pituitary adenoma (NFPA) are rare in paediatric patients. The aim of this study was to describe long-term consequences in adults with GH deficiency (GHD) treated for CD or NFPA during childhood.......Cushing's disease (CD) and non-functioning pituitary adenoma (NFPA) are rare in paediatric patients. The aim of this study was to describe long-term consequences in adults with GH deficiency (GHD) treated for CD or NFPA during childhood....

  12. The influence of thyroid diseases, diabetes mellitus, primary hyperparathyroidism, vitamin B12 deficiency and other comorbid autoimmune diseases on treatment outcome in patients with rheumatoid arthritis: An exploratory cohort study

    DEFF Research Database (Denmark)

    Emamifar, Amir; Jensen Hansen, Inger Marie

    2018-01-01

    To investigate the impact of comorbid diseases on rheumatoid arthritis (RA) outcome. All patients diagnosed with RA since 2006, who were registered in our local Danbio registry, were included in this cohort study. Patients’ demographics, serology results, and Disease Activity Score in 28 joints......-C-reactive protein (DAS28-CRP) at the time of diagnosis and after 4 months of treatment initiation were collected. Patients’ electronic hospital records were evaluated for a positive history of thyroid diseases, diabetes mellitus, primary hyperparathyroidism, vitamin B12 deficiency, and the presence of other...... diagnosed autoimmune diseases. 1035 RA patients were included. The observed prevalence of thyroid diseases was 11.8%, DM 10.4%, primary hyperparathyroidism 2.8%, vitamin B12 deficiency 5.8%, and other diagnosed autoimmune diseases 1.6%. There were significant associations between presence of thyroid...

  13. Immune deficiency vs. immune excess in inflammatory bowel diseases-STAT3 as a rheo-STAT of intestinal homeostasis.

    Science.gov (United States)

    Leppkes, Moritz; Neurath, Markus F; Herrmann, Martin; Becker, Christoph

    2016-01-01

    Genome-wide association studies have provided many genetic alterations, conferring susceptibility to multifactorial polygenic diseases, such as inflammatory bowel diseases. Yet, how specific genetic alterations functionally affect intestinal inflammation often remains elusive. It is noteworthy that a large overlap of genes involved in immune deficiencies with those conferring inflammatory bowel disease risk has been noted. This has provided new arguments for the debate on whether inflammatory bowel disease arises from either an excess or a deficiency in the immune system. In this review, we highlight the functional effect of an inflammatory bowel disease-risk allele, which cannot be deduced from genome-wide association studies data alone. As exemplified by the transcription factor signal transducer and activator of transcription 3 (STAT3), we show that a single gene can have a plethora of effects in various cell types of the gut. These effects may individually contribute to the restoration of intestinal homeostasis on the one hand or pave the way for excessive immunopathology on the other, as an inflammatory "rheo-STAT". © Society for Leukocyte Biology.

  14. Behavioral impairments in animal models for zinc deficiency

    Directory of Open Access Journals (Sweden)

    Simone eHagmeyer

    2015-01-01

    Full Text Available Apart from teratogenic and pathological effects of zinc deficiency such as the occurrence of skin lesions, anorexia, growth retardation, depressed wound healing, altered immune function, impaired night vision, and alterations in taste and smell acuity, characteristic behavioral changes in animal models and human patients suffering from zinc deficiency have been observed. Given that it is estimated that about 17% of the worldwide population are at risk for zinc deficiency and that zinc deficiency is associated with a variety of brain disorders and disease states in humans, it is of major interest to investigate, how these behavioral changes will affect the individual and a putative course of a disease. Thus, here, we provide a state of the art overview about the behavioral phenotypes observed in various models of zinc deficiency, among them environmentally produced zinc deficient animals as well as animal models based on a genetic alteration of a particular zinc homeostasis gene. Finally, we compare the behavioral phenotypes to the human condition of mild to severe zinc deficiency and provide a model, how zinc deficiency that is associated with many neurodegenerative and neuropsychological disorders might modify the disease pathologies.

  15. NHE1 deficiency in liver: Implications for non-alcoholic fatty liver disease

    Energy Technology Data Exchange (ETDEWEB)

    Prasad, Vikram, E-mail: prasadvm@ucmail.uc.edu [Department of Molecular Genetics, Biochemistry, and Microbiology, University of Cincinnati College of Medicine (United States); Chirra, Shivani [Department of Molecular Genetics, Biochemistry, and Microbiology, University of Cincinnati College of Medicine (United States); Kohli, Rohit [Department of Gastroenterology, Hepatology, and Nutrition, Cincinnati Children’s Hospital, University of Cincinnati, Cincinnati, OH 45267 (United States); Shull, Gary E. [Department of Molecular Genetics, Biochemistry, and Microbiology, University of Cincinnati College of Medicine (United States)

    2014-07-25

    Highlights: • FXR, PGC1α and PPARγ levels are upregulated in NHE1 deficient livers. • NHE1 deficiency downregulates expression of pro-lipogenic genes in liver. • Chronic exposure to high-fat diet upregulates hepatic NHE1 expression. • Loss of NHE1 better preserves hepatic insulin signaling in high-fat diet-fed mice. - Abstract: Non-alcoholic fatty liver disease NAFLD is closely associated with the dysregulation of lipid homeostasis. Diet-induced hepatic steatosis, which can initiate NAFLD progression, has been shown to be dramatically reduced in mice lacking the electroneutral Na{sup +}/H{sup +} exchanger NHE1 (Slc9a1). In this study, we investigated if NHE1 deficiency had effects in liver that could contribute to the apparent protection against aberrant lipid accumulation. RT-PCR and immunoblot analyses of wild-type and NHE1-null livers revealed an expression profile that strongly suggested attenuation of both de novo lipogenesis and hepatic stellate cell activation, which is implicated in liver fibrosis. This included upregulation of the farnesoid X receptor FXR, peroxisome proliferator-activated receptor PPARγ, its co-activator PGC1α, and sestrin 2, an antioxidant protein involved in hepatic metabolic homeostasis. Furthermore, expression levels of the pro-lipogenic liver X receptor LXRα, and acetyl CoA carboxylases 1 and 2 were downregulated. These changes were associated with evidence of reduced cellular stress, which persisted even upon exposure to a high-fat diet, and the better preservation of insulin signaling, as evidenced by protein kinase B/Akt phosphorylation (Ser473). These results indicate that NHE1 deficiency may protect against NAFLD pathogenesis, which is significant given the availability of highly specific NHE1 inhibitors.

  16. Autophagic lysosome reformation dysfunction in glucocerebrosidase deficient cells: relevance to Parkinson disease.

    Science.gov (United States)

    Magalhaes, Joana; Gegg, Matthew E; Migdalska-Richards, Anna; Doherty, Mary K; Whitfield, Phillip D; Schapira, Anthony H V

    2016-08-15

    Glucocerebrosidase (GBA1) gene mutations increase the risk of Parkinson disease (PD). While the cellular mechanisms associating GBA1 mutations and PD are unknown, loss of the glucocerebrosidase enzyme (GCase) activity, inhibition of autophagy and increased α-synuclein levels have been implicated. Here we show that autophagy lysosomal reformation (ALR) is compromised in cells lacking functional GCase. ALR is a cellular process controlled by mTOR which regenerates functional lysosomes from autolysosomes formed during macroautophagy. A decrease in phopho-S6K levels, a marker of mTOR activity, was observed in models of GCase deficiency, including primary mouse neurons and the PD patient derived fibroblasts with GBA1 mutations, suggesting that ALR is compromised. Importantly Rab7, a GTPase crucial for endosome-lysosome trafficking and ALR, accumulated in GCase deficient cells, supporting the notion that lysosomal recycling is impaired. Recombinant GCase treatment reversed ALR inhibition and lysosomal dysfunction. Moreover, ALR dysfunction was accompanied by impairment of macroautophagy and chaperone-mediated autophagy, increased levels of total and phosphorylated (S129) monomeric α-synuclein, evidence of amyloid oligomers and increased α-synuclein release. Concurrently, we found increased cholesterol and altered glucosylceramide homeostasis which could compromise ALR. We propose that GCase deficiency in PD inhibits lysosomal recycling. Consequently neurons are unable to maintain the pool of mature and functional lysosomes required for the autophagic clearance of α-synuclein, leading to the accumulation and spread of pathogenic α-synuclein species in the brain. Since GCase deficiency and lysosomal dysfunction occur with ageing and sporadic PD pathology, the decrease in lysosomal reformation may be a common feature in PD. © The Author 2016. Published by Oxford University Press.

  17. NHE1 deficiency in liver: Implications for non-alcoholic fatty liver disease

    International Nuclear Information System (INIS)

    Prasad, Vikram; Chirra, Shivani; Kohli, Rohit; Shull, Gary E.

    2014-01-01

    Highlights: • FXR, PGC1α and PPARγ levels are upregulated in NHE1 deficient livers. • NHE1 deficiency downregulates expression of pro-lipogenic genes in liver. • Chronic exposure to high-fat diet upregulates hepatic NHE1 expression. • Loss of NHE1 better preserves hepatic insulin signaling in high-fat diet-fed mice. - Abstract: Non-alcoholic fatty liver disease NAFLD is closely associated with the dysregulation of lipid homeostasis. Diet-induced hepatic steatosis, which can initiate NAFLD progression, has been shown to be dramatically reduced in mice lacking the electroneutral Na + /H + exchanger NHE1 (Slc9a1). In this study, we investigated if NHE1 deficiency had effects in liver that could contribute to the apparent protection against aberrant lipid accumulation. RT-PCR and immunoblot analyses of wild-type and NHE1-null livers revealed an expression profile that strongly suggested attenuation of both de novo lipogenesis and hepatic stellate cell activation, which is implicated in liver fibrosis. This included upregulation of the farnesoid X receptor FXR, peroxisome proliferator-activated receptor PPARγ, its co-activator PGC1α, and sestrin 2, an antioxidant protein involved in hepatic metabolic homeostasis. Furthermore, expression levels of the pro-lipogenic liver X receptor LXRα, and acetyl CoA carboxylases 1 and 2 were downregulated. These changes were associated with evidence of reduced cellular stress, which persisted even upon exposure to a high-fat diet, and the better preservation of insulin signaling, as evidenced by protein kinase B/Akt phosphorylation (Ser473). These results indicate that NHE1 deficiency may protect against NAFLD pathogenesis, which is significant given the availability of highly specific NHE1 inhibitors

  18. Association of some specific nutrient deficiencies with periodontal disease in elderly people: A systematic literature review.

    NARCIS (Netherlands)

    Putten, G.J. van der; Vanobbergen, J.N.; Visschere, L. De; Schols, J.G.J.H.; Baat, C. de

    2009-01-01

    OBJECTIVE: Deficiency of vitamin B complex, vitamin C, vitamin D, calcium, and magnesium has been associated with periodontal disease. This article systematically reviews the currently available literature on the feasible association of vitamin B complex, vitamin C, vitamin D, calcium, and magnesium

  19. Vitamin D deficiency, oxidative stress and antioxidant status: only weak association seen in the absence of advanced age, obesity or pre-existing disease.

    Science.gov (United States)

    Wang, Erica W; Siu, Parco M; Pang, Marco Y; Woo, Jean; Collins, Andrew R; Benzie, Iris F F

    2017-07-01

    Vitamin D deficiency (plasma 25-hydroxycholecalciferol (25(OH)D)70 % of participants were vitamin D deficient. No significant correlations and no biomarker differences across 25(OH)D quartiles or groups were seen except for total antioxidant status. A weak direct association (r 0·252, Pstress biomarkers in the absence of advanced age, obesity and disease, though some evidence of depleted antioxidant status in those with vitamin D deficiency was seen. Poor antioxidant status may pre-date increased oxidative stress. Study of effects of correction of deficiency on antioxidant status and oxidative stress in vitamin D-deficient but otherwise healthy subjects is needed.

  20. 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

  1. Osteoporosis and Vitamin D Deficiency in Patients with Sickle Cell Disease

    Directory of Open Access Journals (Sweden)

    Zeynep Ozdemir

    2016-07-01

    Full Text Available Aim: Bone disorders such as osteopenia or osteoporosis are the most common clinical manifestations seen in sickle cell disease (SCD with a high of morbidity. There are many reasons, including vitamin D deficiency for the appearance of bone problems. In the present study we aimed to evaluate osteopathy in patients with SCD using bone mineral densitometry (BMD and biochemical indices. Material and Method: 61 patients (29 female, 32 male were included in the study. The age, gender, and biochemical parameters with BMD were evaluated using dual energy X-ray absorptiometry from lumbar vertebrae. According to Z scores, [-2] was considered as osteoporosis. Multivariate analysis was performed to determine the factors influencing BMD. Results: There were a total of 61 SCD patients. The average age was 21.06±5.06 (15-27 years and the mean BMI was 19.15±2.98 kg/m2. 23 patients were osteopenic (11 female, 12 male (37.7% and 26 were osteoporotic (12 female, 13 male (44.3%. Twelve patients (6 female and 6 male (18% had normal Z scores. Vitamin D was found severely deficient (

  2. 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.

  3. ASIC1a Deficient Mice Show Unaltered Neurodegeneration in the Subacute MPTP Model of Parkinson Disease.

    Directory of Open Access Journals (Sweden)

    Daniel Komnig

    Full Text Available Inflammation contributes to the death of dopaminergic neurons in Parkinson disease and can be accompanied by acidification of extracellular pH, which may activate acid-sensing ion channels (ASIC. Accordingly, amiloride, a non-selective inhibitor of ASIC, was protective in an acute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP mouse model of Parkinson disease. To complement these findings we determined MPTP toxicity in mice deficient for ASIC1a, the most common ASIC isoform in neurons. MPTP was applied i.p. in doses of 30 mg per kg on five consecutive days. We determined the number of dopaminergic neurons in the substantia nigra, assayed by stereological counting 14 days after the last MPTP injection, the number of Nissl positive neurons in the substantia nigra, and the concentration of catecholamines in the striatum. There was no difference between ASIC1a-deficient mice and wildtype controls. We are therefore not able to confirm that ASIC1a are involved in MPTP toxicity. The difference might relate to the subacute MPTP model we used, which more closely resembles the pathogenesis of Parkinson disease, or to further targets of amiloride.

  4. 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

  5. Bile acid treatment alters hepatic disease and bile acid transport in peroxisome-deficient PEX2 Zellweger mice

    NARCIS (Netherlands)

    Keane, Megan H.; Overmars, Henk; Wikander, Thomas M.; Ferdinandusse, Sacha; Duran, Marinus; Wanders, Ronald J. A.; Faust, Phyllis L.

    2007-01-01

    The marked deficiency of peroxisomal organelle assembly in the PEX2(-/-) mouse model for Zellweger syndrome provides a unique opportunity to developmentally and biochemically characterize hepatic disease progression and bile acid products. The postnatal survival of homozygous mutants enabled us to

  6. Maternal Antibody-Mediated Disease Enhancement in Type I Interferon-Deficient Mice Leads to Lethal Disease Associated with Liver Damage.

    Directory of Open Access Journals (Sweden)

    Julia María Martínez Gómez

    2016-03-01

    Full Text Available Epidemiological studies have reported that most of the severe dengue cases occur upon a secondary heterologous infection. Furthermore, babies born to dengue immune mothers are at greater risk of developing severe disease upon primary infection with a heterologous or homologous dengue virus (DENV serotype when maternal antibodies reach sub-neutralizing concentrations. These observations have been explained by the antibody mediated disease enhancement (ADE phenomenon whereby heterologous antibodies or sub-neutralizing homologous antibodies bind to but fail to neutralize DENV particles, allowing Fc-receptor mediated entry of the virus-antibody complexes into host cells. This eventually results in enhanced viral replication and heightened inflammatory responses. In an attempt to replicate this ADE phenomenon in a mouse model, we previously reported that upon DENV2 infection 5-week old type I and II interferon (IFN receptors-deficient mice (AG129 born to DENV1-immune mothers displayed enhancement of disease severity characterized by increased virus titers and extensive vascular leakage which eventually led to the animals' death. However, as dengue occurs in immune competent individuals, we sought to reproduce this mouse model in a less immunocompromised background. Here, we report an ADE model that is mediated by maternal antibodies in type I IFN receptor-deficient A129 mice. We show that 5-week old A129 mice born to DENV1-immune mothers succumbed to a DENV2 infection within 4 days that was sub-lethal in mice born to naïve mothers. Clinical manifestations included extensive hepatocyte vacuolation, moderate vascular leakage, lymphopenia, and thrombocytopenia. Anti-TNFα therapy totally protected the mice and correlated with healthy hepatocytes. In contrast, blocking IL-6 did not impact the virus titers or disease outcome. This A129 mouse model of ADE may help dissecting the mechanisms involved in dengue pathogenesis and evaluate the efficacy of

  7. [Efficacy and safety of hormonal therapy with androgens (androgel) in men with erectile dysfunction, partial androgen deficiency of aging male and cardiovascular diseases].

    Science.gov (United States)

    Kalinchenko, S Iu; Vorslov, L O; Aglamazian, N L; Morgunov, L Iu

    2007-01-01

    Partial androgen deficiency of aging male (PADAM) manifests with sexual dysfunction and is associated with many diseases, primarily, cardiovascular. After the age of 30-40 a testosterone level falls 1-2% a year. The number of men with testosterone deficiency grows from 8% in 40-60-year-olds to 85% at the age over 80 years. Low testosterone correlates with such risk factors of cardiovascular diseases as dyslipidemia, atherosclerosis, low fibrinolysis, insulin resistance and abdominal obesity. Correction of androgenic deficiency can be conducted with the drug androgel which represents a new system of transdermal testosterone delivery. In contrast to vasoactive drugs, androgel affects pathogenetic mechanisms of erectile dysfunction and thus attenuates factors of cardiovascular risk. Androgel is used externally and is more effective than intramuscular and oral analogues. Also, the drug improves lipid spectrum. By activating lipolysis, testosterone reduces the amount of visceral fat thus lowering insulin resistance. A vasodilating effect of androgel positively influences cardiovascular system and penile vessels. The drug acts fast, is effective and safe. Therefore, it can be recommended for correction of erectile dysfunction in patients with old age androgen deficiency and concurrent cardiovascular diseases.

  8. Transaldolase deficiency: a new cause of hydrops fetalis and neonatal multi-organ disease.

    Science.gov (United States)

    Valayannopoulos, Vassili; Verhoeven, Nanda M; Mention, Karine; Salomons, Gajja S; Sommelet, Danièle; Gonzales, Marie; Touati, Guy; de Lonlay, Pascale; Jakobs, Cornelis; Saudubray, Jean-Marie

    2006-11-01

    Transaldolase (TALDO) deficiency is a newly recognized metabolic disease, which has been reported so far in 2 patients presenting with liver failure and cirrhosis. We report a new sibship of 4 infants born to the same consanguineous parents; all presented at birth or in the antenatal period with dysmorphic features, cutis laxa and hypertrichosis, hepatomegaly, splenomegaly, liver failure, hemolytic anemia, thrombocytopenia, and genitourinary malformations. The clinical courses were variable: the first child died of liver failure at 4 months of age; the second pregnancy was medically terminated at 28 weeks gestation because of hydrops fetalis with oligohydramnios. The third child is doing well at age 7 with liver fibrosis and mild kidney failure. The fourth child is now 21 months old and has hepatosplenomegaly, mild anemia, and thrombocytopenia. Urine assessment of polyols showed elevations of erythritol, arabitol, and ribitol consistent with TALDO deficiency. TALDO activity was undetectable in the patients' tissues, and mutation in the TALDO1 gene was found in the 4 patients.

  9. Iodine Deficiency and Excess Coexist in China and Induce Thyroid Dysfunction and Disease: A Cross-Sectional Study

    Science.gov (United States)

    Meng, Fangang; Liu, Shoujun; Fan, Zhipeng; Wu, Junhua; Sun, Dianjun

    2014-01-01

    Background In spite of the salt iodization, iodine deficiency disorders (IDD) have not been sustainably eliminated in China. There are coastal areas with low iodized salt coverage rates (iodine nutrition is inadequate) and other areas with excessive amounts of iodine in the drinking water. Objective This study aimed to clarify the association of iodine deficiencies resulting from a low coverage rate of iodized salt, excess iodine intake from drinking water with thyroid function and disease in adults. Design A cross-sectional study was conducted in adults in different iodine nutrition areas in three provinces in China. Results The prevalence of thyroid nodules was 15.52%, 8.66% and 22.17% in the iodine excess, sufficient and deficient groups, respectively. The prevalence of subclinical hypothyroidism was 20.09%, 10.41%, and 2.25% in the excess, sufficient and deficient iodine groups, respectively. The prevalence of subclinical hyperthyroidism and overt hyperthyroidism in the iodine deficient group was higher than that in the iodine excess group ( = 9.302, p = 0.002) and iodine sufficient group ( = 7.553, p = 0.006). Thyroid-stimulating hormone (TSH) was significantly correlated with excess iodine intake (β = 1.764,P = 0.001) and deficient iodine intake (β = −1.219, P = 0.028). Conclusions Thyroid nodules are more likely to be present in the iodine excess and deficient areas than in the iodine sufficient areas. Subclinical hyperthyroidism and overt hyperthyroidism are more likely to be prevalent in the iodine deficient areas than in the iodine excess or sufficient areas. Subclinical hypothyroidism is more likely to be prevalent in the high iodine intake areas than in the iodine deficient or sufficient areas. Median TSH may be deemed as an alternative indicator for monitoring the iodine nutrition status of the adult population in iodine excess and deficient areas. PMID:25375854

  10. Iodine deficiency and excess coexist in china and induce thyroid dysfunction and disease: a cross-sectional study.

    Directory of Open Access Journals (Sweden)

    Yang Du

    Full Text Available BACKGROUND: In spite of the salt iodization, iodine deficiency disorders (IDD have not been sustainably eliminated in China. There are coastal areas with low iodized salt coverage rates (iodine nutrition is inadequate and other areas with excessive amounts of iodine in the drinking water. OBJECTIVE: This study aimed to clarify the association of iodine deficiencies resulting from a low coverage rate of iodized salt, excess iodine intake from drinking water with thyroid function and disease in adults. DESIGN: A cross-sectional study was conducted in adults in different iodine nutrition areas in three provinces in China. RESULTS: The prevalence of thyroid nodules was 15.52%, 8.66% and 22.17% in the iodine excess, sufficient and deficient groups, respectively. The prevalence of subclinical hypothyroidism was 20.09%, 10.41%, and 2.25% in the excess, sufficient and deficient iodine groups, respectively. The prevalence of subclinical hyperthyroidism and overt hyperthyroidism in the iodine deficient group was higher than that in the iodine excess group ([Formula: see text] = 9.302, p = 0.002 and iodine sufficient group ([Formula: see text] = 7.553, p = 0.006. Thyroid-stimulating hormone (TSH was significantly correlated with excess iodine intake (β = 1.764,P = 0.001 and deficient iodine intake (β = -1.219, P = 0.028. CONCLUSIONS: Thyroid nodules are more likely to be present in the iodine excess and deficient areas than in the iodine sufficient areas. Subclinical hyperthyroidism and overt hyperthyroidism are more likely to be prevalent in the iodine deficient areas than in the iodine excess or sufficient areas. Subclinical hypothyroidism is more likely to be prevalent in the high iodine intake areas than in the iodine deficient or sufficient areas. Median TSH may be deemed as an alternative indicator for monitoring the iodine nutrition status of the adult population in iodine excess and deficient areas.

  11. Heart failure in patients with kidney disease and iron deficiency; the role of iron therapy.

    Science.gov (United States)

    Cases Amenós, Aleix; Ojeda López, Raquel; Portolés Pérez, José María

    Chronic kidney disease and anaemia are common in heart failure (HF) and are associated with a worse prognosis in these patients. Iron deficiency is also common in patients with HF and increases the risk of morbidity and mortality, regardless of the presence or absence of anaemia. While the treatment of anaemia with erythropoiesis-stimulating agents in patients with HF have failed to show a benefit in terms of morbidity and mortality, treatment with IV iron in patients with HF and reduced ejection fraction and iron deficiency is associated with clinical improvement. In a posthoc analysis of a clinical trial, iron therapy improved kidney function in patients with HF and iron deficiency. In fact, the European Society of Cardiology's recent clinical guidelines on HF suggest that in symptomatic patients with reduced ejection fraction and iron deficiency, treatment with IV ferric carboxymaltose should be considered to improve symptoms, the ability to exercise and quality of life. Iron plays a key role in oxygen storage (myoglobin) and in energy metabolism, and there are pathophysiological bases that explain the beneficial effect of IV iron therapy in patients with HF. All these aspects are reviewed in this article. Copyright © 2017 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

  12. The association of vitamin D deficiency with non-alcoholic fatty liver disease

    Directory of Open Access Journals (Sweden)

    Metin Küçükazman

    2014-08-01

    Full Text Available OBJECTIVE: Vitamin D deficiency has been related to diabetes, hypertension, hyperlipidemia and peripheral vascular disease. In this study, we aimed to investigate the role of vitamin D status in non-alcoholic fatty liver disease. METHODS: We included 211 consecutive subjects to examine the presence of non-alcoholic fatty liver disease. Of these subjects, 57 did not have non-alcoholic fatty liver disease and 154 had non-alcoholic fatty liver disease. RESULTS: The non-alcoholic fatty liver disease group had significantly higher fasting blood glucose (p = 0.005, uric acid (p = 0.001, aspartate aminotransferase (p<0.001, alanine aminotransferase (p<0.001, γ-glutamyltransferase (p<0.0001, alkaline phosphatase (p = 0.028, HbA1c (p<0.001, ferritin (p<0.001, insulin (p = 0.016, C-peptide (p = 0.001, HOMA-IR (p = 0.003, total cholesterol (p = 0.001, triglyceride (p = 0.001 and white blood cell (p = 0.04 levels. In contrast, the non-alcoholic fatty liver disease group had significantly lower 25(OHD levels (12.3±8.9 ng/dl, p<0.001 compared with those of the control group (20±13.6 ng/dl. CONCLUSIONS: In this study, we found lower serum 25(OHD levels in patients with non-alcoholic fatty liver disease than in subjects without non-alcoholic fatty liver disease. To establish causality between vitamin D and non-alcoholic fatty liver disease, further interventional studies with a long-term follow-up are needed.

  13. Iron-Deficiency Anemia

    Medline Plus

    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 ...

  14. Mucosal-associated invariant T cells are numerically and functionally deficient in patients with mycobacterial infection and reflect disease activity.

    Science.gov (United States)

    Kwon, Yong-Soo; Cho, Young-Nan; Kim, Moon-Ju; Jin, Hye-Mi; Jung, Hyun-Ju; Kang, Jeong-Hwa; Park, Ki-Jeong; Kim, Tae-Jong; Kee, Hae Jin; Kim, Nacksung; Kee, Seung-Jung; Park, Yong-Wook

    2015-05-01

    Mucosal-associated invariant T (MAIT) cells contribute to protection against certain microorganism infections. The aims of this study were to examine the levels of MAIT cells in pulmonary tuberculosis (TB) and nontuberculous mycobacteria (NTM) lung disease patients, to evaluate the clinical relevance of MAIT cell levels, and to investigate the functions of MAIT cells. Patients with pulmonary TB (n = 35), NTM (n = 29), and healthy controls (n = 75) were enrolled in the study. MAIT cell levels and functions were measured by flow cytometry. Circluating MAIT cell levels were found to be reduced in TB and NTM patients. MAIT cell deficiency reflects a variety of clinical conditions. In particular, MAIT cell numbers were significantly correlated with sputum AFB positivity, extent of disease, hemoglobin levels, lymphocyte counts, CRP and ESR levels. MAIT cells in TB patients failed to produce interferon-γ irrespective of the mode of stimulation, whereas NTM patients displayed a defect in MR1-dependent signaling pathway. Notably, an elevated expression of programmed death-1 was also associated with MAIT cell deficiency in TB. This study shows that MAIT cells are numerically and functionally deficient in TB and NTM patients and these deficiencies could contribute to immune system dysreguation in mycobacterial infection. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. Importance and management of micronutrient deficiencies in patients with Alzheimer’s disease

    Directory of Open Access Journals (Sweden)

    Cardoso BR

    2013-05-01

    Full Text Available Bárbara Rita Cardoso,1 Cristiane Cominetti,2 Silvia Maria Franciscato Cozzolino11Faculty of Pharmaceutical Sciences, University of São Paulo (USP, São Paulo, Brazil; 2Faculty of Nutrition, Federal University of Goiás, Goiás, BrazilAbstract: Alzheimer’s disease (AD is the most common form of dementia, and it generally affects the elderly. It has been suggested that diet is an intensively modifiable lifestyle factor that might reduce the risk of AD. Because epidemiological studies generally report the potential neuronal protective effects of various micronutrients, the aim of this study was to perform a literature review on the major nutrients that are related to AD, including selenium, vitamins C and E, transition metals, vitamin D, B-complex vitamins, and omega-3 fatty acids.Keywords: Alzheimer’s disease, nutritional deficiencies, diet, oxidative stress, lipid, vitamins

  16. Evaluation of Cholinergic Deficiency in Preclinical Alzheimer’s Disease Using Pupillometry

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    Shaun Frost

    2017-01-01

    Full Text Available Cortical cholinergic deficiency is prominent in Alzheimer’s disease (AD, and published findings of diminished pupil flash response in AD suggest that this deficiency may extend to the visual cortical areas and anterior eye. Pupillometry is a low-cost, noninvasive technique that may be useful for monitoring cholinergic deficits which generally lead to memory and cognitive disorders. The aim of the study was to evaluate pupillometry for early detection of AD by comparing the pupil flash response (PFR in AD (N=14 and cognitively normal healthy control (HC, N=115 participants, with the HC group stratified according to high (N=38 and low (N=77 neocortical amyloid burden (NAB. Constriction phase PFR parameters were significantly reduced in AD compared to HC (maximum acceleration p<0.05, maximum velocity p<0.0005, average velocity p<0.005, and constriction amplitude p<0.00005. The high-NAB HC subgroup had reduced PFR response cross-sectionally, and also a greater decline longitudinally, compared to the low-NAB subgroup, suggesting changes to pupil response in preclinical AD. The results suggest that PFR changes may occur in the preclinical phase of AD. Hence, pupillometry has a potential as an adjunct for noninvasive, cost-effective screening for preclinical AD.

  17. Isolated acquired factor VII deficiency: review of the literature.

    Science.gov (United States)

    Mulliez, Sylvie M N; Devreese, Katrien M J

    2016-04-01

    Isolated acquired factor VII (FVII) deficiency is a rare haemorrhagic disorder. We report what is currently known about the pathogenesis, clinical features, diagnosis, treatment and prognosis of acquired FVII deficiency. We performed a literature search and included all articles published between 1980 and August 2015. Acquired FVII deficiency has been reported in 42 patients. There are well-established clinical diseases associated with acquired FVII deficiency, most notably infections, malignancy and haematological stem cell transplantation. The exact pathogenesis of the diseases is still unknown, but different pathophysiological hypotheses have been suggested. The clinical manifestation of acquired FVII deficiency varies greatly in severity; asymptomatic course as well as severe life-threatening bleeding diathesis and fatal bleedings have been described.

  18. Bone pain and extremely low bone mineral density due to severe vitamin D deficiency in celiac disease

    NARCIS (Netherlands)

    Rabelink, N.M.; Westgeest, H.M.; Bravenboer, N.; Jacobs, M.A.J.M.; Lips, P.T.A.M.

    2011-01-01

    Case report A 29-year-old wheelchair-bound woman was presented to us by the gastroenterologist with suspected osteomalacia. She had lived in the Netherlands all her life and was born of Moroccan parents. Her medical history revealed iron deficiency, growth retardation, and celiac disease, for which

  19. Variants of cognitive deficiency depending on the clinical characteristics of the disease in patients with paranoid schizophrenia

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    G. G. Lebedeva

    2015-01-01

    Full Text Available Pecific aspects of cognitive impairments in patients with paranoid schizophrenia depending on the clinical characteristics of the disease have been studied. One hundred and thirty patients were examined. A clinico-psychological, experimental psychological and statistical methods were used. Three main types of cognitive deficiency with paranoid schizophrenia, associated with the onset, disease duration, and severity of psychiatric symptomology : 1 long-term course of the disease accompanied by the average level of clinical symptomology associated with abnormal attention and visuospatial functions; 2 late onset of the disease and unexpressed clinical symptomology combined with memory impairments; 3 acute onset and early age combined with the absence of cognitive impairments.

  20. Rational Management of Iron-Deficiency Anaemia in Inflammatory Bowel Disease

    Science.gov (United States)

    Vikner, Malene Elbaek; Weiss, Günter

    2018-01-01

    Anaemia is the most frequent, though often neglected, comorbidity of inflammatory bowel disease (IBD). Here we want to briefly present (1) the burden of anaemia in IBD, (2) its pathophysiology, which mostly arises from bleeding-associated iron deficiency, followed by (3) diagnostic evaluation of anaemia, (4) a balanced overview of the different modes of iron replacement therapy, (5) evidence for their therapeutic efficacy and subsequently, (6) an updated recommendation for the practical management of anaemia in IBD. Following the introduction of various intravenous iron preparations over the last decade, questions persist about when to use these preparations as opposed to traditional and other novel oral iron therapeutic agents. At present, oral iron therapy is generally preferred for patients with quiescent IBD and mild iron-deficiency anaemia. However, in patients with flaring IBD that hampers intestinal iron absorption and in those with inadequate responses to or side effects with oral preparations, intravenous iron supplementation is the therapy of choice, although information on the efficacy of intravenous iron in patients with active IBD and anaemia is scare. Importantly, anaemia in IBD is often multifactorial and a careful diagnostic workup is mandatory for optimized treatment. Nevertheless, limited information is available on optimal therapeutic start and end points for treatment of anaemia. Of note, neither oral nor intravenous therapies seem to exacerbate the clinical course of IBD. However, additional prospective studies are still warranted to determine the optimal therapy in complex conditions such as IBD. PMID:29342861

  1. Duodenal histopathology and laboratory deficiencies related to bone metabolism in coeliac disease.

    Science.gov (United States)

    Posthumus, Lotte; Al-Toma, Abdul

    2017-08-01

    Coeliac disease (CD) is a chronic immune-mediated small intestine enteropathy precipitated by gluten in genetically predisposed individuals. Adult presentation is often atypical and malabsorption of vitamins and minerals is common, with a consequent disturbance of bone metabolism. We aim to evaluate laboratory deficiencies related to bone metabolism and the relationship between severity of histological damage and degree of bone mass loss at diagnosis of CD. A retrospective cross-sectional study of 176 adult coeliac patients was carried out. All patients fulfilled the histopathological criteria for CD. Biochemical data were analysed (calcium/phosphate/alkaline-phosphatase/vitamin D/parathormone). Duodenal histology was classified according to the Marsh classification. Bone mass density (BMD) at the lumbar and femoral regions measured by dual X-ray absorptiometry. A P-value of less than 0.05 was considered significant. No correlation was found between the presence of gastrointestinal symptoms and the Marsh histopathological stage (P>0.05). Vitamin D deficiency was most common (44.5%), whereas only 5.7% had hypocalcaemia. Calcium was lower (Pcoeliac patients older than 30 years, evaluation of bone biomarkers and dual X-ray absorptiometry examination should be considered.

  2. Coronary artery disease and its association with Vitamin D deficiency

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    Ramesh Aggarwal

    2016-01-01

    Full Text Available Coronary artery disease (CAD has become the latest scourge of humankind and referred to in this article as CAD, is the end result of the accumulation of atheromatous plaques within the walls of coronary arteries that supply the myocardium, a process also known as atherosclerosis and manifests mostly in the form of chronic stable angina or acute coronary syndrome. Vitamin D has attracted considerable interest recently due to its role in a number of extraskeletal disease processes including multiple sclerosis, malignancies, diabetes mellitus, and CAD. It is also known as sunshine vitamin due to its production in the body following exposure to ultraviolet rays, and it is a unique vitamin as it acts like a hormone with its receptor present in a wide range of tissues including endothelium, which is the important mediator of atherosclerosis and subsequent CAD. A large number of studies conducted in the past have provided the basic scientific framework and this article attempts to explore the role of Vitamin D deficiency in the pathogenesis of CAD and stresses the need for further research to fill up gap in our knowledge.

  3. Dietary Intake of Vitamins in Different Options of Treatment in Chronic Kidney Disease: Is There a Deficiency?

    Science.gov (United States)

    Jankowska, M; Szupryczyńska, N; Dębska-Ślizień, A; Borek, P; Kaczkan, M; Rutkowski, B; Małgorzewicz, S

    2016-06-01

    The importance of diet in the management of kidney transplantation (KT), as well as other treatment options of chronic kidney disease (CKD), is generally acknowledged. However, data regarding vitamin intake are very limited. Vitamins are essential in maintaining good nutritional status and preventing many chronic complications. It is still not clear which treatment modality imposes the highest risk of dietary vitamin deficiency and whether successful KT reverses such a threat. We performed this observational study to assess dietary intake of vitamins in CKD patients: after successful KT, not yet dialyzed (ND), treated with hemodialysis (HD), and with peritoneal dialysis (PD). A total of 202 patients were recruited (45 KT, 50 ND, 45 HD, and 62 PD). Vitamin intakes were evaluated through the use of a 24-hour dietary recall and processed with the use of a computerized database. Each record was evaluated by a skilled dietitian. In general, vitamin intakes in all study groups were comparable, with KT and ND groups manifesting lower risk of deficiency than HD and PD groups. The content of fat-soluble vitamins in diet was insufficient, with remarkably high prevalence of vitamin D deficiency. Mean intakes of water-soluble vitamins were close to recommended, with the exception of folic acid, which was profoundly deficient in all groups. CKD patients are at risk of inadequate vitamin intake. Vitamin D and folic acid are universally deficient in diet. KT patients have the most satisfactory content of vitamins in their diet, whereas HD individuals are at highest risk of deficiency. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. 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 ...

  5. [Vitamin D deficiency in chronic liver disease, clinical-epidemiological analysis and report after vitamin d supplementation].

    Science.gov (United States)

    Fernández Fernández, Nereida; Linares Torres, Pedro; Joáo Matias, Diana; Jorquera Plaza, Francisco; Olcoz Goñi, Jose Luis

    2016-05-01

    Vitamin D (VD) is known to have multiple extra-skeletal health functions. There is emerging interest in exploring the relationship between vitamin D and chronic liver disease (CLD). To determine the prevalence of VD deficiency in patients with CLD in our setting and to assess whether VD supplementation influences plasma levels and is associated with improved liver function. We conducted a study in 2 phases. First, we analysed clinical and epidemiological characteristics in 94 patients with CLD; second, different doses of calcifediol (25-OH-VD) were administered to patients with VD deficiency (C (7.75ng/mL). After VD supplementation, optimal serum levels were achieved in 94% of patients and significant improvements were observed in platelet count, albumin levels (P<.05) and functional status assessed by the Child-Pugh scale (P<.05). Given the high prevalence of VD deficiency or insufficiency, the need for screening should be considered in the population with CLD. VD supplementation could be safe and effective. Copyright © 2015 Elsevier España, S.L.U. and AEEH y AEG. All rights reserved.

  6. 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 ...

  7. Iron deficiency across chronic inflammatory conditions: International expert opinion on definition, diagnosis, and management.

    Science.gov (United States)

    Cappellini, Maria Domenica; Comin-Colet, Josep; de Francisco, Angel; Dignass, Axel; Doehner, Wolfram; Lam, Carolyn S; Macdougall, Iain C; Rogler, Gerhard; Camaschella, Clara; Kadir, Rezan; Kassebaum, Nicholas J; Spahn, Donat R; Taher, Ali T; Musallam, Khaled M

    2017-10-01

    Iron deficiency, even in the absence of anemia, can be debilitating, and exacerbate any underlying chronic disease, leading to increased morbidity and mortality. Iron deficiency is frequently concomitant with chronic inflammatory disease; however, iron deficiency treatment is often overlooked, partially due to the heterogeneity among clinical practice guidelines. In the absence of consistent guidance across chronic heart failure, chronic kidney disease and inflammatory bowel disease, we provide practical recommendations for iron deficiency to treating physicians: definition, diagnosis, and disease-specific diagnostic algorithms. These recommendations should facilitate appropriate diagnosis and treatment of iron deficiency to improve quality of life and clinical outcomes. © 2017 The Authors American Journal of Hematology Published by Wiley Periodicals, Inc.

  8. Property of lysosomal storage disease associated with midbrain pathology in the central nervous system of Lamp-2-deficient mice.

    Science.gov (United States)

    Furuta, Akiko; Kikuchi, Hisae; Fujita, Hiromi; Yamada, Daisuke; Fujiwara, Yuuki; Kabuta, Tomohiro; Nishino, Ichizo; Wada, Keiji; Uchiyama, Yasuo

    2015-06-01

    Lysosome-associated membrane protein-2 (LAMP-2) is the gene responsible for Danon disease, which is characterized by cardiomyopathy, autophagic vacuolar myopathy, and variable mental retardation. To elucidate the function of LAMP-2 in the central nervous system, we investigated the neuropathological changes in Lamp-2-deficient mice. Immunohistochemical observations revealed that Lamp-1 and cathepsin D-positive lysosomal structures increased in the large neurons of the mouse brain. Ubiquitin-immunoreactive aggregates and concanavalin A-positive materials were detected in these neurons. By means of ultrastructural studies, we found various-shaped accumulations, including lipofuscin, glycolipid-like materials, and membranous structures, in the neurons and glial cells of Lamp-2-deficient brains. In deficient mice, glycogen granules accumulated in hepatocyte lysosomes but were not observed in neurons. These pathological features indicate lysosomal storage disease; however, the findings are unlikely a consequence of deficiency of a single lysosomal enzyme. Although previous study results have shown a large amount of autophagic vacuoles in parenchymal cells of the visceral organs, these findings were rarely detected in the brain tissue except for some axons in the substantia nigra, in which abundant activated microglial cells with increased lipid peroxidation were observed. Thus, LAMP-2 in the central nervous system has a possible role in the degradation of the various macromolecules in lysosomes and an additional function concerning protection from oxidative stress, especially in the substantia nigra. Copyright © 2015 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  9. Lysosomal storage disease 2 - Pompe's disease

    NARCIS (Netherlands)

    van der Ploeg, Ans T.; Reuser, Arnold J. J.

    2008-01-01

    Pompe's disease, glycogen-storage disease type II, and acid maltase deficiency are alternative names for the same metabolic disorder. It is a pan-ethnic autosomal recessive trait characterised by acid alpha-glucosidase deficiency leading to lysosomal glycogen storage. Pompe's disease is also

  10. Iron-Deficiency Anemia

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    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 ...

  11. Iron-Deficiency Anemia

    Medline Plus

    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) ...

  12. 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.

  13. Acquired factor VII deficiency associated with acute myeloid leukemia.

    Science.gov (United States)

    Anoun, Soumaya; Lamchahab, Mouna; Oukkache, Bouchra; Qachouh, Maryam; Benchekroun, Said; Quessar, Asmaa

    2015-04-01

    Isolated acquired factor VII deficiency is a rare coagulopathy. It has been reported in 31 patients with malignancy, sepsis, postoperatively, aplastic anemia, and during bone marrow transplantation. We discuss, through a new case of acquired factor VII deficiency, the characteristics of this disease when it is associated with acute myeloid leukemia. Acquired factor VII deficiency in hematological diseases can be caused by intensive chemotherapy, infections, or hepatic dysfunction. The best treatment in developing countries remains corticosteroids associated with plasma exchange, frozen plasma, and antibiotics.

  14. 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.

  15. Iron Deficiency Anemia in Relation to Respiratory Disease and Social Behaviors In Low-Income Infants in France.

    Science.gov (United States)

    Honig, Alice Sterling

    1993-01-01

    Examined a sample of 177 infants (age 9 through 12 months) with iron deficiency anemia (IDA) from low-income French, African, and North African Muslim families in Paris. Found a higher than normal incidence of otitis media and respiratory diseases such as bronchitis among the infants. Also examined the relationship between infant IDA and child…

  16. Lipidomic and Transcriptomic Basis of Lysosomal Dysfunction in Progranulin Deficiency

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    Bret M. Evers

    2017-09-01

    Full Text Available Defective lysosomal function defines many neurodegenerative diseases, such as neuronal ceroid lipofuscinoses (NCL and Niemann-Pick type C (NPC, and is implicated in Alzheimer’s disease (AD and frontotemporal lobar degeneration (FTLD-TDP with progranulin (PGRN deficiency. Here, we show that PGRN is involved in lysosomal homeostasis and lipid metabolism. PGRN deficiency alters lysosome abundance and morphology in mouse neurons. Using an unbiased lipidomic approach, we found that brain lipid composition in humans and mice with PGRN deficiency shows disease-specific differences that distinguish them from normal and other pathologic groups. PGRN loss leads to an accumulation of polyunsaturated triacylglycerides, as well as a reduction of diacylglycerides and phosphatidylserines in fibroblast and enriched lysosome lipidomes. Transcriptomic analysis of PGRN-deficient mouse brains revealed distinct expression patterns of lysosomal, immune-related, and lipid metabolic genes. These findings have implications for the pathogenesis of FTLD-TDP due to PGRN deficiency and suggest lysosomal dysfunction as an underlying mechanism.

  17. Hepatic glucose-6-phosphatase-α deficiency leads to metabolic reprogramming in glycogen storage disease type Ia.

    Science.gov (United States)

    Cho, Jun-Ho; Kim, Goo-Young; Mansfield, Brian C; Chou, Janice Y

    2018-04-15

    Glycogen storage disease type Ia (GSD-Ia) is caused by a deficiency in glucose-6-phosphatase-α (G6Pase-α or G6PC), a key enzyme in endogenous glucose production. This autosomal recessive disorder is characterized by impaired glucose homeostasis and long-term complications of hepatocellular adenoma/carcinoma (HCA/HCC). We have shown that hepatic G6Pase-α deficiency-mediated steatosis leads to defective autophagy that is frequently associated with carcinogenesis. We now show that hepatic G6Pase-α deficiency also leads to enhancement of hepatic glycolysis and hexose monophosphate shunt (HMS) that can contribute to hepatocarcinogenesis. The enhanced hepatic glycolysis is reflected by increased lactate accumulation, increased expression of many glycolytic enzymes, and elevated expression of c-Myc that stimulates glycolysis. The increased HMS is reflected by increased glucose-6-phosphate dehydrogenase activity and elevated production of NADPH and the reduced glutathione. We have previously shown that restoration of hepatic G6Pase-α expression in G6Pase-α-deficient liver corrects metabolic abnormalities, normalizes autophagy, and prevents HCA/HCC development in GSD-Ia. We now show that restoration of hepatic G6Pase-α expression normalizes both glycolysis and HMS in GSD-Ia. Moreover, the HCA/HCC lesions in L-G6pc-/- mice exhibit elevated levels of hexokinase 2 (HK2) and the M2 isoform of pyruvate kinase (PKM2) which play an important role in aerobic glycolysis and cancer cell proliferation. Taken together, hepatic G6Pase-α deficiency causes metabolic reprogramming, leading to enhanced glycolysis and elevated HMS that along with impaired autophagy can contribute to HCA/HCC development in GSD-Ia. Published by Elsevier Inc.

  18. Activation-induced cytidine deaminase deficiency causes organ-specific autoimmune disease.

    Directory of Open Access Journals (Sweden)

    Koji Hase

    Full Text Available Activation-induced cytidine deaminase (AID expressed by germinal center B cells is a central regulator of somatic hypermutation (SHM and class switch recombination (CSR. Humans with AID mutations develop not only the autosomal recessive form of hyper-IgM syndrome (HIGM2 associated with B cell hyperplasia, but also autoimmune disorders by unknown mechanisms. We report here that AID-/- mice spontaneously develop tertiary lymphoid organs (TLOs in non-lymphoid tissues including the stomach at around 6 months of age. At a later stage, AID-/- mice develop a severe gastritis characterized by loss of gastric glands and epithelial hyperplasia. The disease development was not attenuated even under germ-free (GF conditions. Gastric autoantigen -specific serum IgM was elevated in AID-/- mice, and the serum levels correlated with the gastritis pathological score. Adoptive transfer experiments suggest that autoimmune CD4+ T cells mediate gastritis development as terminal effector cells. These results suggest that abnormal B-cell expansion due to AID deficiency can drive B-cell autoimmunity, and in turn promote TLO formation, which ultimately leads to the propagation of organ-specific autoimmune effector CD4+ T cells. Thus, AID plays an important role in the containment of autoimmune diseases by negative regulation of autoreactive B cells.

  19. 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 ...

  20. The "multiple hormone deficiency" theory of aging: is human senescence caused mainly by multiple hormone deficiencies?

    Science.gov (United States)

    Hertoghe, T

    2005-12-01

    In the human body, the productions, levels and cell receptors of most hormones progressively decline with age, gradually putting the body into various states of endocrine deficiency. The circadian cycles of these hormones also change, sometimes profoundly, with time. In aging individuals, the well-balanced endocrine system can fall into a chaotic condition with losses, phase-advancements, phase delays, unpredictable irregularities of nycthemeral hormone cycles, in particular in very old or sick individuals. The desynchronization makes hormone activities peak at the wrong times and become inefficient, and in certain cases health threatening. The occurrence of multiple hormone deficits and spilling through desynchronization may constitute the major causes of human senescence, and they are treatable causes. Several arguments can be put forward to support the view that senescence is mainly a multiple hormone deficiency syndrome: First, many if not most of the signs, symptoms and diseases (including cardiovascular diseases, cancer, obesity, diabetes, osteoporosis, dementia) of senescence are similar to physical consequences of hormone deficiencies and may be caused by hormone deficiencies. Second, most of the presumed causes of senescence such as excessive free radical formation, glycation, cross-linking of proteins, imbalanced apoptosis system, accumulation of waste products, failure of repair systems, deficient immune system, may be caused or favored by hormone deficiencies. Even genetic causes such as limits to cell proliferation (such as the Hayflick limit of cell division), poor gene polymorphisms, premature telomere shortening and activation of possible genetic "dead programs" may have links with hormone deficiencies, being either the consequence, the cause, or the major favoring factor of hormone deficiencies. Third, well-dosed and -balanced hormone supplements may slow down or stop the progression of signs, symptoms, or diseases of senescence and may often

  1. 25 Hydroxyvitamin D Deficiency and Its Relationship to Autoimmune Thyroid Disease in the Elderly

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    Giovanna Muscogiuri

    2016-08-01

    Full Text Available Background: Low 25(OH vitamin D levels have been associated with several autoimmune diseases and recently with autoimmune thyroiditis (AT. The aim of the study was to investigate the association of AT with low 25(OH vitamin D levels in the elderly. Methods: One hundred sixty-eight elderly subjects (mean age: 81.6 ± 9.4 years were enrolled. Serum levels of 25(OH vitamin D, anti-thyroid peroxidase (TPO-Ab, anti-thyroglobulin (TG-Ab antibodies, free triiodothyronine (FT3, free thyroxine (FT4 and thyroid stimulating hormone (TSH were measured. Results: The prevalence of AT was significantly higher in subjects with vitamin D deficiency (25(OH vitamin D < 20 ng/mL when compared with subjects with normal 25(OH vitamin D (25(OH vitamin D ≥ 20 ng/mL levels (28% vs. 8%, respectively, p = 0.002. Patients with AT and vitamin D deficiency had a comparable hormonal profile compared to patients with AT and vitamin D sufficiency in terms of TSH (p = 0.39, FT3 (p = 0.30, FT4 (p = 0.31, TG-Ab (0.44 and TPO-Ab (0.35. Interestingly, a significant correlation between 25(OH vitamin D and TPO-Ab (r = −0.27, p = 0.03 and FT3 (r = 0.35, p = 0.006 has been found in subjects with AT while no correlation was found between 25(OH vitamin D levels and TG-Ab (r = −0.15, p = 0.25, TSH (r = −0.014, p = 0.09 and FT4 (r = 0.13, p = 0.32. Conclusions: These findings suggest that vitamin D deficiency was significantly associated with AT in the elderly. Therefore, the screening for AT should be suggested in subjects with vitamin D deficiency.

  2. Maternal micronutrient deficiency leads to alteration in the kidney proteome in rat pups.

    Science.gov (United States)

    Ahmad, Shadab; Basak, Trayambak; Anand Kumar, K; Bhardwaj, Gourav; Lalitha, A; Yadav, Dilip K; Chandak, Giriraj Ratan; Raghunath, Manchala; Sengupta, Shantanu

    2015-09-08

    Maternal nutritional deficiency significantly perturbs the offspring's physiology predisposing them to metabolic diseases during adulthood. Vitamin B12 and folate are two such micronutrients, whose deficiency leads to elevated homocysteine levels. We earlier generated B12 and/or folate deficient rat models and using high-throughput proteomic approach, showed that maternal vitamin B12 deficiency modulates carbohydrate and lipid metabolism in the liver of pups through regulation of PPAR signaling pathway. In this study, using similar approach, we identified 26 differentially expressed proteins in the kidney of pups born to mothers fed with vitamin B12 deficient diet while only four proteins were identified in the folate deficient group. Importantly, proteins like calreticulin, cofilin 1 and nucleoside diphosphate kinase B that are involved in the functioning of the kidney were upregulated in B12 deficient group. Our results hint towards a larger effect of vitamin B12 deficiency compared to that of folate presumably due to greater elevation of homocysteine in vitamin B12 deficient group. In view of widespread vitamin B12 and folate deficiency and its association with several diseases like anemia, cardiovascular and renal diseases, our results may have large implications for kidney diseases in populations deficient in vitamin B12 especially in vegetarians and the elderly people.This article is part of a Special Issue entitled: Proteomics in India. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. ANALYSIS OF BILIARY CHOLESTEROL LEVELS IN IRON-DEFICIENT PATIENTS OPERATED FOR GALLSTONE DISEASE

    Directory of Open Access Journals (Sweden)

    R. Kannan

    2017-01-01

    Full Text Available BACKGROUND Gallstone disease is a common gastrointestinal problem in day-to-day practice. The old concept that a typical gallstone sufferer is fat, fertile, flatulent female of 50. This is partially true as the disease has been found in women soon after their first delivery who are thin and underweight and in males also. Conditions that favour the formation of cholesterol gallstones are super saturation of bile with cholesterol, kinetically favourable nucleation and presence of cholesterol crystals in the gallbladder long enough to agglomerate into a stone. Recent studies have defined the role of trace elements (Fe, Ca, Zn and Cu and defective pH in the formation of gallstones. The aim of the study is to determine the association of iron deficiency in super saturation of bile. This cross-sectional study of 50 patients was conducted over a period of 12 months in the Department of General Surgery, Kilpauk Medical College, Chennai, India. Biliary cholesterol and serum cholesterol were compared in iron deficient and non-iron deficient patients having gallstones. A low serum iron level is a factor in bile super saturation with respect to cholesterol leading to gallstone formation. MATERIALS AND METHODS This study was conducted over a period of 12 months in the Department of General Surgery, Kilpauk Medical College, Chennai, India. 50 patients suffering from cholelithiasis confirmed by USG were divided into two groups based on serum iron values. Group A consists of patients with normal serum iron (non-anaemic and Group B of patients with less than normal serum iron (anaemic. RESULTS Serum total cholesterol of the patients of cholelithiasis was not different among groups categorised based on serum iron levels. There were no significant variations in the serum cholesterol contents of both the groups. Also, there was no significant variation of the above parameter in the male and female patients. CONCLUSION Though, it is difficult to draw a causal

  4. Genetics Home Reference: glucose-6-phosphate dehydrogenase deficiency

    Science.gov (United States)

    ... deficiency Encyclopedia: Glucose-6-phosphate dehydrogenase test Encyclopedia: Hemolytic anemia Encyclopedia: Newborn jaundice Health Topic: Anemia Health Topic: G6PD Deficiency Health Topic: Newborn Screening Genetic and Rare Diseases Information Center (1 link) Glucose-6-phosphate dehydrogenase ...

  5. Topical administration of interleukin-1 receptor antagonist as a therapy for aqueous-deficient dry eye in autoimmune disease.

    Science.gov (United States)

    Vijmasi, Trinka; Chen, Feeling Y T; Chen, Ying Ting; Gallup, Marianne; McNamara, Nancy

    2013-01-01

    Dry eye is commonly associated with autoimmune diseases such as Sjögren's syndrome (SS), in which exocrinopathy of the lacrimal gland leads to aqueous tear deficiency and keratoconjunctivitis sicca (KCS). KCS is among the most common and debilitating clinical manifestations of SS that is often recalcitrant to therapy. We established mice deficient in the autoimmune regulator (Aire) gene as a model for autoimmune-mediated aqueous-deficient dry eye. In Aire-deficient mice, CD4+ T cells represent the main effector cells and local signaling via the interleukin-1 (IL-1/IL-1R1) pathway provides an essential link between autoreactive CD4+ T cells and ocular surface disease. In the current study, we evaluated the efficacy of topical administration of IL-1R1 antagonist (IL-1RA) anakinra in alleviating ocular surface damage resulting from aqueous-deficient dry eye in the setting of autoimmune disease. We compared the effect of commercially available IL-1R1 antagonist, anakinra (50 μg/mL concentration) to that of carboxymethylcellulose (CMC) vehicle control as a treatment for dry eye. Age-matched, Aire-deficient mice were treated three times daily with anakinra or CMC vehicle for 14 days using side-by-side (n = 4 mice/group) and paired-eye (n = 5) comparisons. We assessed (1) ocular surface damage with lissamine green staining; (2) tear secretion with wetting of phenol-red threads; (3) goblet cell (GC) mucin glycosylation with lectin histochemistry; (4) immune cell infiltration using anti-F4/80, CD11c, and CD4 T cell antibodies; and (5) gene expression of cornified envelope protein, Small Proline-Rich Protein-1B (SPRR1B) with real-time quantitative polymerase chain reaction. Aire-deficient mice treated with anakinra experienced significant improvements in ocular surface integrity and tear secretion. After 7 days of treatment, lissamine green staining decreased in eyes treated with anakinra compared to an equivalent increase in staining following treatment with CMC vehicle

  6. CD8+ T-Cell Deficiency, Epstein-Barr Virus Infection, Vitamin D Deficiency, and Steps to Autoimmunity: A Unifying Hypothesis

    Directory of Open Access Journals (Sweden)

    Michael P. Pender

    2012-01-01

    Full Text Available CD8+ T-cell deficiency is a feature of many chronic autoimmune diseases, including multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus, Sjögren's syndrome, systemic sclerosis, dermatomyositis, primary biliary cirrhosis, primary sclerosing cholangitis, ulcerative colitis, Crohn's disease, psoriasis, vitiligo, bullous pemphigoid, alopecia areata, idiopathic dilated cardiomyopathy, type 1 diabetes mellitus, Graves' disease, Hashimoto's thyroiditis, myasthenia gravis, IgA nephropathy, membranous nephropathy, and pernicious anaemia. It also occurs in healthy blood relatives of patients with autoimmune diseases, suggesting it is genetically determined. Here it is proposed that this CD8+ T-cell deficiency underlies the development of chronic autoimmune diseases by impairing CD8+ T-cell control of Epstein-Barr virus (EBV infection, with the result that EBV-infected autoreactive B cells accumulate in the target organ where they produce pathogenic autoantibodies and provide costimulatory survival signals to autoreactive T cells which would otherwise die in the target organ by activation-induced apoptosis. Autoimmunity is postulated to evolve in the following steps: (1 CD8+ T-cell deficiency, (2 primary EBV infection, (3 decreased CD8+ T-cell control of EBV, (4 increased EBV load and increased anti-EBV antibodies, (5 EBV infection in the target organ, (6 clonal expansion of EBV-infected autoreactive B cells in the target organ, (7 infiltration of autoreactive T cells into the target organ, and (8 development of ectopic lymphoid follicles in the target organ. It is also proposed that deprivation of sunlight and vitamin D at higher latitudes facilitates the development of autoimmune diseases by aggravating the CD8+ T-cell deficiency and thereby further impairing control of EBV. The hypothesis makes predictions which can be tested, including the prevention and successful treatment of chronic autoimmune diseases by controlling EBV infection.

  7. Vitamin D deficiency plays an important role in cardiac disease and affects patient outcome: Still a myth or a fact that needs exploration?

    Directory of Open Access Journals (Sweden)

    Zaher Fanari

    2015-10-01

    Full Text Available There is increasing evidence that a low vitamin D status may be an important and hitherto neglected factor of cardiovascular disease. This review is an overview of the current body of literature, and presents evidence of the mechanisms through which vitamin D deficiency affects the cardiovascular system in general and the heart in particular. Available data indicate that the majority of congestive heart failure patients have 25-hydroxyvitamin D deficiency. Furthermore, the low serum 25-hydroxyvitamin D level has a higher impact on hypertension, coronary artery disease an on the occurrence of relevant cardiac events. A serum 25-hydroxyvitamin D level below 75 nmol/l (30 ng/l is generally regarded as vitamin D insufficiency in both adults and children, while a level below 50 nmol/l (20 ng/l is considered deficiency. Levels below 50 nmol/l (20 ng/l are linked independently to cardiovascular morbidity and mortality.

  8. Vitamin D deficiency aggravates chronic kidney disease progression after ischemic acute kidney injury.

    Directory of Open Access Journals (Sweden)

    Janaína Garcia Gonçalves

    Full Text Available Despite a significant improvement in the management of chronic kidney disease (CKD, its incidence and prevalence has been increasing over the years. Progressive renal fibrosis is present in CKD and involves the participation of several cytokines, including Transforming growth factor-β1 (TGF-β1. Besides cardiovascular diseases and infections, several studies show that Vitamin D status has been considered as a non-traditional risk factor for the progression of CKD. Given the importance of vitamin D in the maintenance of essential physiological functions, we studied the events involved in the chronic kidney disease progression in rats submitted to ischemia/reperfusion injury under vitamin D deficiency (VDD.Rats were randomized into four groups: Control; VDD; ischemia/reperfusion injury (IRI; and VDD+IRI. At the 62 day after sham or IRI surgery, we measured inulin clearance, biochemical variables and hemodynamic parameters. In kidney tissue, we performed immunoblotting to quantify expression of Klotho, TGF-β, and vitamin D receptor (VDR; gene expression to evaluate renin, angiotensinogen, and angiotensin-converting enzyme; and immunohistochemical staining for ED1 (macrophages, type IV collagen, fibronectin, vimentin, and α-smooth mucle actin. Histomorphometric studies were performed to evaluate fractional interstitial area.IRI animals presented renal hypertrophy, increased levels of mean blood pressure and plasma PTH. Furthermore, expansion of the interstitial area, increased infiltration of ED1 cells, increased expression of collagen IV, fibronectin, vimentin and α-actin, and reduced expression of Klotho protein were observed. VDD deficiency contributed to increased levels of plasma PTH as well as for important chronic tubulointerstitial changes (fibrosis, inflammatory infiltration, tubular dilation and atrophy, increased expression of TGF-β1 and decreased expression of VDR and Klotho protein observed in VDD+IRI animals.Through inflammatory

  9. Clinical features of GH deficiency and effects of 3 years of GH replacement in adults with controlled Cushing's disease

    DEFF Research Database (Denmark)

    Höybye, Charlotte; Ragnarsson, Oskar; Jönsson, Peter J

    2010-01-01

    Patients in remission from Cushing's disease (CD) have many clinical features that are difficult to distinguish from those of concomitant GH deficiency (GHD). In this study, we evaluated the features of GHD in a large cohort of controlled CD patients, and assessed the effect of GH treatment....

  10. 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)

  11. A new glucocerebrosidase-deficient neuronal cell model provides a tool to probe pathophysiology and therapeutics for Gaucher disease.

    Science.gov (United States)

    Westbroek, Wendy; Nguyen, Matthew; Siebert, Marina; Lindstrom, Taylor; Burnett, Robert A; Aflaki, Elma; Jung, Olive; Tamargo, Rafael; Rodriguez-Gil, Jorge L; Acosta, Walter; Hendrix, An; Behre, Bahafta; Tayebi, Nahid; Fujiwara, Hideji; Sidhu, Rohini; Renvoise, Benoit; Ginns, Edward I; Dutra, Amalia; Pak, Evgenia; Cramer, Carole; Ory, Daniel S; Pavan, William J; Sidransky, Ellen

    2016-07-01

    Glucocerebrosidase is a lysosomal hydrolase involved in the breakdown of glucosylceramide. Gaucher disease, a recessive lysosomal storage disorder, is caused by mutations in the gene GBA1 Dysfunctional glucocerebrosidase leads to accumulation of glucosylceramide and glycosylsphingosine in various cell types and organs. Mutations in GBA1 are also a common genetic risk factor for Parkinson disease and related synucleinopathies. In recent years, research on the pathophysiology of Gaucher disease, the molecular link between Gaucher and Parkinson disease, and novel therapeutics, have accelerated the need for relevant cell models with GBA1 mutations. Although induced pluripotent stem cells, primary rodent neurons, and transfected neuroblastoma cell lines have been used to study the effect of glucocerebrosidase deficiency on neuronal function, these models have limitations because of challenges in culturing and propagating the cells, low yield, and the introduction of exogenous mutant GBA1 To address some of these difficulties, we established a high yield, easy-to-culture mouse neuronal cell model with nearly complete glucocerebrosidase deficiency representative of Gaucher disease. We successfully immortalized cortical neurons from embryonic null allele gba(-/-) mice and the control littermate (gba(+/+)) by infecting differentiated primary cortical neurons in culture with an EF1α-SV40T lentivirus. Immortalized gba(-/-) neurons lack glucocerebrosidase protein and enzyme activity, and exhibit a dramatic increase in glucosylceramide and glucosylsphingosine accumulation, enlarged lysosomes, and an impaired ATP-dependent calcium-influx response; these phenotypical characteristics were absent in gba(+/+) neurons. This null allele gba(-/-) mouse neuronal model provides a much-needed tool to study the pathophysiology of Gaucher disease and to evaluate new therapies. © 2016. Published by The Company of Biologists Ltd.

  12. A new glucocerebrosidase-deficient neuronal cell model provides a tool to probe pathophysiology and therapeutics for Gaucher disease

    Directory of Open Access Journals (Sweden)

    Wendy Westbroek

    2016-07-01

    Full Text Available Glucocerebrosidase is a lysosomal hydrolase involved in the breakdown of glucosylceramide. Gaucher disease, a recessive lysosomal storage disorder, is caused by mutations in the gene GBA1. Dysfunctional glucocerebrosidase leads to accumulation of glucosylceramide and glycosylsphingosine in various cell types and organs. Mutations in GBA1 are also a common genetic risk factor for Parkinson disease and related synucleinopathies. In recent years, research on the pathophysiology of Gaucher disease, the molecular link between Gaucher and Parkinson disease, and novel therapeutics, have accelerated the need for relevant cell models with GBA1 mutations. Although induced pluripotent stem cells, primary rodent neurons, and transfected neuroblastoma cell lines have been used to study the effect of glucocerebrosidase deficiency on neuronal function, these models have limitations because of challenges in culturing and propagating the cells, low yield, and the introduction of exogenous mutant GBA1. To address some of these difficulties, we established a high yield, easy-to-culture mouse neuronal cell model with nearly complete glucocerebrosidase deficiency representative of Gaucher disease. We successfully immortalized cortical neurons from embryonic null allele gba−/− mice and the control littermate (gba+/+ by infecting differentiated primary cortical neurons in culture with an EF1α-SV40T lentivirus. Immortalized gba−/− neurons lack glucocerebrosidase protein and enzyme activity, and exhibit a dramatic increase in glucosylceramide and glucosylsphingosine accumulation, enlarged lysosomes, and an impaired ATP-dependent calcium-influx response; these phenotypical characteristics were absent in gba+/+ neurons. This null allele gba−/− mouse neuronal model provides a much-needed tool to study the pathophysiology of Gaucher disease and to evaluate new therapies.

  13. β-Galactosidase Deficiency in Colombia

    Directory of Open Access Journals (Sweden)

    Alfredo Uribe PhD

    2015-05-01

    Full Text Available β-Galactosidase (BGal is the first enzyme involved in the catabolism of sphingolipids. Two pathologies have been directly associated with its deficiency: GM1 gangliosidosis and Morquio B. Morquio B is among the rarest types of mucopolysaccharidosis (MPS. We aim to document the β-galactosidase deficiency in Colombia. We evaluated leukocytes from 1492 healthy Colombian individuals and 923 patients, referred between 2005 and August 2014. Dried blood spot (DBS samples from the same number of patients were evaluated. β-Galactosidase was measured with 4-methylumbelliferyl-β- d -galactoside. As a control enzyme, the total hexosaminidase activity was also evaluated. We identified 14 patients with GM1 gangliosidosis, 5 patients with Morquio B, and 1 patient with I-cell disease. We could establish a reference value for Bgal in Colombian leukocyte samples. GM1 gangliosidosis is the main pathology associated with a direct deficiency of BGal. The high number of patients found with MPS IVB indicates that there are patients who could be misdiagnosed due to an unawareness of the disease.

  14. Association of glucose-6-phosphate dehydrogenase deficiency and X-linked chronic granulomatous disease in a child with anemia and recurrent infections

    OpenAIRE

    Agudelo-Florez, P.; Costa-Carvalho, Beatriz Tavares [UNIFESP; Lopez, J. A.; Redher, J.; Newburger, P. E.; Alla-Saad, S. T.; Condino-Neto, A.

    2004-01-01

    Patients with severe leukocyte G6PD deficiency may present with impairment of NADPH oxidase activity and a history of recurrent infections, mimicking the phenotype of chronic granulomatous disease. We report herein a child with recurrent infections who initially received the diagnosis of G6PD deficiency. His erythrocyte G6PD activity was reduced: 1.8 U/g Hb (normal: 12.1 +/- 2.1 U/g Hb). Further studies revealed that G6PD activity in neutrophils, mononuclear leukocytes, and Epstein-Barr virus...

  15. The Evidence-Based Evaluation of Iron Deficiency Anemia.

    Science.gov (United States)

    Hempel, Eliana V; Bollard, Edward R

    2016-09-01

    Anemia is a prevalent disease with multiple possible etiologies and resultant complications. Iron deficiency anemia is a common cause of anemia and is typically due to insufficient intake, poor absorption, or overt or occult blood loss. Distinguishing iron deficiency from other causes of anemia is integral to initiating the appropriate treatment. In addition, identifying the underlying cause of iron deficiency is also necessary to help guide management of these patients. We review the key components to an evidence-based, cost-conscious evaluation of suspected iron deficiency anemia. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Vitamin B12 deficiency evaluation and treatment in severe dry eye disease with neuropathic ocular pain.

    Science.gov (United States)

    Ozen, Serkan; Ozer, Murat Atabey; Akdemir, Mehmet Orçun

    2017-06-01

    This study aims to understand the effect of vitamin B12 deficiency on neuropathic ocular pain (NOP) and symptoms in patients with dry eye disease (DED). Patients with severe DED (without receiving topical artificial tears treatment) and ocular pain were enrolled (n = 90). Patients with severe DED and vitamin B12 deficiency (group 1, n = 45) received parenteral vitamin B12 supplement + topical treatment (artificial tears treatment + cyclosporine), and patients with severe DED and normal serum vitamin B12 level (group 2, n = 45) received only topical treatment (artificial tears treatment + cyclosporine). Patients were evaluated by the ocular surface disease index (OSDI) questionnaire, 3rd question (have you experienced painful or sore eyes during last week?) score of OSDI as a pain determiner and pain frequency measure), tear break up time (TBUT), and Schirmer's type 1 test. We compared the groups' OSDI, TBUT, and Schirmer's test recordings at the first visit and after 12 weeks retrospectively. The OSDI score, 3rd OSDI question score, TBUT, and Schirmer's test results improved after 12 weeks (p treatment. The mean score changes between the groups were not statistically significant; however, the decrease in the OSDI questionnaire score (-30.80 ±5.24) and 3rd OSDI question score (-2.82 ±0.53) were remarkable in group 1 (Table 2). The mean TBUT increase was +7.98 ±2.90 s and Schirmer's test result increase was +12.16 ±2.01 mm in group 1. The mean TBUT increase was +6.18 ±1.49 s and Schirmer's test result increase was +6.71 ±1.47 mm in group 2. These findings indicate that vitamin B12 deficiency is related with NOP. It may be important to consider measuring the serum vitamin B12 level in patients with severe DED presenting with resistant ocular pain despite taking topical treatment.

  17. Magnesium deficiency and increased inflammation: current perspectives

    Directory of Open Access Journals (Sweden)

    Nielsen FH

    2018-01-01

    Full Text Available Forrest H Nielsen Research Nutritionist Consultant, Grand Forks, ND, USA Abstract: Animal studies have shown that magnesium deficiency induces an inflammatory response that results in leukocyte and macrophage activation, release of inflammatory cytokines and acute-phase proteins, and excessive production of free radicals. Animal and in vitro studies indicate that the primary mechanism through which magnesium deficiency has this effect is through increasing cellular Ca2+, which is the signal that results in the priming of cells to give the inflammatory response. Primary pro-inflammatory cytokines such as tumor necrosis factor-α and interleukin (IL-1; the messenger cytokine IL-6; cytokine responders E-selectin, intracellular adhesion molecule-1 and vascular cell adhesion molecule-1; and acute-phase reactants C-reactive protein and fibrinogen have been determined to associate magnesium deficiency with chronic low-grade inflammation (inflammatory stress. When magnesium dietary intake, supplementation, and/or serum concentration suggest/s the presence of magnesium deficiency, it often is associated with low-grade inflammation and/or with pathological conditions for which inflammatory stress is considered a risk factor. When magnesium intake, supplementation, and/or serum concentration suggest/s an adequate status, magnesium generally has not been found to significantly affect markers of chronic low-grade inflammation or chronic disease. The consistency of these findings can be modified by other nutritional and metabolic factors that affect inflammatory and oxidative stress. In spite of this, findings to date provide convincing evidence that magnesium deficiency is a significant contributor to chronic low-grade inflammation that is a risk factor for a variety of pathological conditions such as cardiovascular disease, hypertension, and diabetes. Because magnesium deficiency commonly occurs in countries where foods rich in magnesium are not consumed in

  18. Brain Insulin Resistance and Deficiency as Therapeutic Targets in Alzheimer's Disease

    Science.gov (United States)

    de la Monte, Suzanne M

    2012-01-01

    Alzheimer's disease [AD] is the most common cause of dementia in North America. Despite 30+ years of intense investigation, the field lacks consensus regarding the etiology and pathogenesis of sporadic AD, and therefore we still do not know the best strategies for treating and preventing this debilitating and costly disease. However, growing evidence supports the concept that AD is fundamentally a metabolic disease with substantial and progressive derangements in brain glucose utilization and responsiveness to insulin and insulin-like growth factor [IGF] stimulation. Moreover, AD is now recognized to be heterogeneous in nature, and not solely the end-product of aberrantly processed, misfolded, and aggregated oligomeric amyloid-beta peptides and hyperphosphorylated tau. Other factors, including impairments in energy metabolism, increased oxidative stress, inflammation, insulin and IGF resistance, and insulin/IGF deficiency in the brain should be incorporated into all equations used to develop diagnostic and therapeutic approaches to AD. Herein, the contributions of impaired insulin and IGF signaling to AD-associated neuronal loss, synaptic disconnection, tau hyperphosphorylation, amyloid-beta accumulation, and impaired energy metabolism are reviewed. In addition, we discuss current therapeutic strategies and suggest additional approaches based on the hypothesis that AD is principally a metabolic disease similar to diabetes mellitus. Ultimately, our ability to effectively detect, monitor, treat, and prevent AD will require more efficient, accurate and integrative diagnostic tools that utilize clinical, neuroimaging, biochemical, and molecular biomarker data. Finally, it is imperative that future therapeutic strategies for AD abandon the concept of uni-modal therapy in favor of multi-modal treatments that target distinct impairments at different levels within the brain insulin/IGF signaling cascades. PMID:22329651

  19. Inflammatory Markers: C-Reactive Protein, Erythrocyte Sedimentation Rate, and Leukocyte Count in Vitamin D Deficient Patients with and without Chronic Kidney Disease

    Directory of Open Access Journals (Sweden)

    Ibrahim Yildirim

    2013-01-01

    Full Text Available Although some studies revealed a positive relationship between vitamin D3 deficiency and inflammatory markers, there have been also many studies that failed to find this relationship. The aim of this large scaled study is to determine the association between the level of plasma 25 hydroxy vitamin D3 [25-(OH D3] and inflammatory markers in the general population without chronic kidney disease (CKD and in patients with CKD. Participants with simultaneously measured inflammatory markers and 25-(OH D3 levels were retrospectively analyzed (n=1897. The incidence of all-cause inflammation infection, hospitalization, chronic renal failure, and vitamin B12 deficiency was evaluated. The medians of serum creatinine levels in subjects without renal failure were lower in 25-(OH D3 deficient group. Patients with CKD were more likely to have vitamin D3 deficiency compared with normal GFR. 25-(OH D3 levels were associated with a greater incidence of all-cause hospitalization, hypoalbuminemia, and vitamin B12 deficiency. However, there was no relationship between inflammatory markers and vitamin D3 levels. In 25-(OH D3 deficient patients, inflammatory markers can be related to other inflammatory and infectious status such as malnutrition and cachexia. We believed that there must be a relationship between vitamin deficiency and inflammatory markers due to other causes than low 25-(OH D3 status.

  20. Advances in clinical determinants and neurological manifestations of B vitamin deficiency in adults.

    Science.gov (United States)

    Sechi, GianPietro; Sechi, Elia; Fois, Chiara; Kumar, Neeraj

    2016-05-01

    B vitamin deficiency is a leading cause of neurological impairment and disability throughout the world. Multiple B vitamin deficiencies often coexist, and thus an understanding of the complex relationships between the different biochemical pathways regulated in the brain by these vitamins may facilitate prompter diagnosis and improved treatment. Particular populations at risk for multiple B vitamin deficiencies include the elderly, people with alcoholism, patients with heart failure, patients with recent obesity surgery, and vegetarians/vegans. Recently, new clinical settings that predispose individuals to B vitamin deficiency have been highlighted. Moreover, other data indicate a possible pathogenetic role of subclinical chronic B vitamin deficiency in neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. In light of these findings, this review examines the clinical manifestations of B vitamin deficiency and the effect of B vitamin deficiency on the adult nervous system. The interrelationships of multiple B vitamin deficiencies are emphasized, along with the clinical phenotypes related to B vitamin deficiencies. Recent advances in the clinical determinants and diagnostic clues of B vitamin deficiency, as well as the suggested therapies for B vitamin disorders, are described. © The Author(s) 2016. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  1. 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.

  2. Vitamin D deficiency: What does it mean for chronic obstructive pulmonary disease (COPD)? a compherensive review for pulmonologists.

    Science.gov (United States)

    Kokturk, Nurdan; Baha, Ayse; Oh, Yeon-Mok; Young Ju, Jung; Jones, Paul W

    2018-02-01

    Vitamin D deficiency and Chronic Obstructive Pulmonary Disease (COPD) are both under-recognized health problems, world-wide. Although Vitamin D has long been known for calcemic effects it also has less known noncalcemic effects. Recent data have shown that Vitamin D deficiency is highly prevalent in patients with COPD and correlates with forced expiratory volume in one second (FEV 1 ) and FEV 1 decline. The objective of this work was to review the current literature on vitamin D deficiency in relation with COPD. A literature search, using the words "vitamin D" and "COPD", was undertaken in Pubmed database. The noncalcemic effects of vitamin D relating with COPD may be summarised as increasing antimicrobial peptide production, regulation of inflammatory response and airway remodelling. Vitamin D inhibits the production of several proinflammatory cytokines and leads to suppression Th1 and Th17 responses which may be involved in the pathogenesis of COPD. Vitamin D insufficiency may also contribute to chronic respiratory infections and airway colonization so returning vitamin D concentrations to an optimal range in patients with COPD might reduce bacterial load and concomitant exacerbations.Vitamin D is also important for COPD-related comorbodities such as osteoporosis, muscle weakness and cardiovascular diseases. Data about the effect of Vitamin D supplementation on those comorbidities in relation with COPD are been scarce. Improving the blood level of Vitamin D into the desired range may have a beneficial effect bones and muscles, but more studies are needed to test to test that hypothesis. © 2017 John Wiley & Sons Ltd.

  3. Clinical management of salivary deficiency: A review article

    International Nuclear Information System (INIS)

    AlSaif, K. M

    1991-01-01

    The physical, chemical and antibacterial properties of saliva provide protection to human dentition against dental diseases, Therefore, salivary deficiency has to be managed carefully. The causes of saliva deficiency are many and varied. It is worth mentioning that saliva flow rate is normally affected by physiologic condition, such as eating, resting, sleeping, cold or hot season etc. In this paper the protective role of saliva, etiologiy of saliva deficiency and its clinical management are discussed. (author

  4. Sod1 deficiency reduces incubation time in mouse models of prion disease.

    Directory of Open Access Journals (Sweden)

    Shaheen Akhtar

    Full Text Available Prion infections, causing neurodegenerative conditions such as Creutzfeldt-Jakob disease and kuru in humans, scrapie in sheep and BSE in cattle are characterised by prolonged and variable incubation periods that are faithfully reproduced in mouse models. Incubation time is partly determined by genetic factors including polymorphisms in the prion protein gene. Quantitative trait loci studies in mice and human genome-wide association studies have confirmed that multiple genes are involved. Candidate gene approaches have also been used and identified App, Il1-r1 and Sod1 as affecting incubation times. In this study we looked for an association between App, Il1-r1 and Sod1 representative SNPs and prion disease incubation time in the Northport heterogeneous stock of mice inoculated with the Chandler/RML prion strain. No association was seen with App, however, significant associations were seen with Il1-r1 (P = 0.02 and Sod1 (P<0.0001 suggesting that polymorphisms at these loci contribute to the natural variation observed in incubation time. Furthermore, following challenge with Chandler/RML, ME7 and MRC2 prion strains, Sod1 deficient mice showed highly significant reductions in incubation time of 20, 13 and 24%, respectively. No differences were detected in Sod1 expression or activity. Our data confirm the protective role of endogenous Sod1 in prion disease.

  5. Natural history of succinic semialdehyde dehydrogenase deficiency through adulthood

    NARCIS (Netherlands)

    Lapalme-Remis, S.; Lewis, E.C.; De Meulemeester, C.; Chakraborty, P.; Gibson, K.M.; Torres, C.; Guberman, A.; Salomons, G.; Jakobs, C.; Ali-Ridha, A.; Parviz, M.; Pearl, P.L.

    2015-01-01

    Objective: The natural history of succinic semialdehyde dehydrogenase (SSADH) deficiency in adulthood is unknown; we elucidate the clinical manifestations of the disease later in life. Methods: A 63-year-old man with long-standing intellectual disability was diagnosed with SSADH deficiency following

  6. Vitamins for the soul: John Bowlby's thesis of maternal deprivation, biomedical metaphors and the deficiency model of disease.

    Science.gov (United States)

    Duniec, Eduardo; Raz, Mical

    2011-03-01

    In 1951 John Bowlby, British psychoanalyst and child psychiatrist, published his now famous report, Maternal Care and Mental Health, commissioned by the World Health Organization. In this report, Bowlby coined the term 'maternal deprivation', which quickly permeated into Western psychiatry and psychology. The implications of Bowlby's writings, while widely criticized and contested, generated a considerable amount of research and brought about significant changes in perceptions of separation between children and their mothers. This article examines the origins of the 'maternal deprivation' hypothesis, focusing on how the deficiency theory of disease influenced psychiatric discourse, and framed Bowlby's theory of maternal care. We argue that developments in paediatric medicine, and particularly in the field of nutritional deficiencies, provided Bowlby a prototype for conceptualizing his early views on the psychological needs of children and the development of psychopathology.

  7. 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

  8. Heart failure in patients with kidney disease and iron deficiency: The role of iron therapy

    Directory of Open Access Journals (Sweden)

    Aleix Cases Amenós

    2017-11-01

    Full Text Available Chronic kidney disease and anaemia are common in heart failure (HF and are associated with a worse prognosis in these patients. Iron deficiency is also common in patients with HF and increases the risk of morbidity and mortality, regardless of the presence or absence of anaemia. While the treatment of anaemia with erythropoiesis-stimulating agents in patients with HF have failed to show a benefit in terms of morbidity and mortality, treatment with IV iron in patients with HF and reduced ejection fraction and iron deficiency is associated with clinical improvement. In a post hoc analysis of a clinical trial, iron therapy improved kidney function in patients with HF and iron deficiency. In fact, the European Society of Cardiology's recent clinical guidelines on HF suggest that in symptomatic patients with reduced ejection fraction and iron deficiency, treatment with IV ferric carboxymaltose should be considered to improve symptoms, the ability to exercise and quality of life. Iron plays a key role in oxygen storage (myoglobin and in energy metabolism, and there are pathophysiological bases that explain the beneficial effect of IV iron therapy in patients with HF. All these aspects are reviewed in this article. Resumen: La enfermedad renal crónica y la anemia son frecuentes en la insuficiencia cardíaca (IC y su presencia se asocia con un peor pronóstico en estos pacientes. La ferropenia es frecuente en pacientes con IC y aumenta el riesgo de morbimortalidad, independientemente de la presencia o no de anemia. Mientras el tratamiento de la anemia con agentes estimuladores de la eritropoyesis en pacientes con IC no ha demostrado un beneficio sobre la morbimortalidad, el tratamiento con hierro intravenoso (iv en pacientes con IC y fracción de eyección disminuida y déficit de hierro se asocia con una mejoría clínica. Además, en un análisis post hoc de un ensayo clínico, la ferroterapia mejoró la función renal en pacientes con IC y

  9. 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...

  10. Immune Deficiency Disease' of Undetermined Aetiology in Infancy

    African Journals Online (AJOL)

    1974-04-06

    Apr 6, 1974 ... The case of a young female child with a combined immuno- deficiency ... was present, but no other stigmata of Turner's syndrome were noted. Generalised lymphadenopathy and a 2-finger hepatosplenomegaly were found. There was a purulent dis<:harge from drainage tubes placed in both middle ears.

  11. 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.

  12. Metabolomics Approach Reveals Integrated Metabolic Network Associated with Serotonin Deficiency

    Science.gov (United States)

    Weng, Rui; Shen, Sensen; Tian, Yonglu; Burton, Casey; Xu, Xinyuan; Liu, Yi; Chang, Cuilan; Bai, Yu; Liu, Huwei

    2015-07-01

    Serotonin is an important neurotransmitter that broadly participates in various biological processes. While serotonin deficiency has been associated with multiple pathological conditions such as depression, schizophrenia, Alzheimer’s disease and Parkinson’s disease, the serotonin-dependent mechanisms remain poorly understood. This study therefore aimed to identify novel biomarkers and metabolic pathways perturbed by serotonin deficiency using metabolomics approach in order to gain new metabolic insights into the serotonin deficiency-related molecular mechanisms. Serotonin deficiency was achieved through pharmacological inhibition of tryptophan hydroxylase (Tph) using p-chlorophenylalanine (pCPA) or genetic knockout of the neuronal specific Tph2 isoform. This dual approach improved specificity for the serotonin deficiency-associated biomarkers while minimizing nonspecific effects of pCPA treatment or Tph2 knockout (Tph2-/-). Non-targeted metabolic profiling and a targeted pCPA dose-response study identified 21 biomarkers in the pCPA-treated mice while 17 metabolites in the Tph2-/- mice were found to be significantly altered compared with the control mice. These newly identified biomarkers were associated with amino acid, energy, purine, lipid and gut microflora metabolisms. Oxidative stress was also found to be significantly increased in the serotonin deficient mice. These new biomarkers and the overall metabolic pathways may provide new understanding for the serotonin deficiency-associated mechanisms under multiple pathological states.

  13. [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.

  14. Performance of the Androgen Deficiency in Aging Male ...

    African Journals Online (AJOL)

    failure, chronic liver disease, chronic renal failure, tuberculosis, chronic obstructive pulmonary diseases, acquired immunodeficiency syndrome and malignancy. Relevant socio- demographic and diabetes-related information were documented. Clinical evaluation of androgen deficiency. Participants completed the original ...

  15. [Vitamin D deficiency in childhood: an opportunity for prevention].

    Science.gov (United States)

    López-González, Desirée; Méndez-Sánchez, Lucía; Guagnelli, Miguel Ángel; Clark, Patricia

    The prevalence of vitamin D deficiency in the pediatric population has increased in recent years and continues to be underdiagnosed and undertreated. According to data from the "ENSANUT 2006" (National Health and Nutrition Survey), the prevalence of vitamin D deficiency in Mexico was 16% in children aged 2-12 years. Vitamin D plays a critical role in the formation and bone homeostasis and consequently on growth. Its deficiency is clearly associated with diseases such as rickets and osteomalacia, and it has been linked to other diseases such as obesity, metabolic syndrome, diabetes, cancer, respiratory infections and immune system disease. Specific risk groups have been described in the medical literature for vitamin D deficiency in which supplementation may offer a benefit. Currently, there is still controversy in defining the serum levels of proficiency and dose supplementation. In Mexico, the daily suggested intake of vitamin D is 5.6μg (224 IU), which is significantly lower than the recommendations in the U.S. and Europe (i.e., between 400 and 1000 IU/day). An increase in vitamin D deficiency has been reported in recent years. There is no consensus regarding the sufficiency levels of vitamin D. Cut-off values vary from 20 to 30ng/ml. Therefore, the objective of this review was to provide an overview of the problem in the pediatric population and to describe the groups at risk, as well as to analyze the current recommendations for vitamin D supplementation. Vitamin D deficiency was considered rare in Mexico according to the National Institute of Medical Science and Nutrition Salvador Zubirán. Lack of evidence did not help to establish the international recommended daily intake. Currently, vitamin D deficiency must be recognized as a health problem, worthy of attention and action. We suggest that prospective studies are carried out in our country where the relationship between serum vitamin D deficiency and poor bone mineralization will be established. Copyright

  16. Therapeutics: Gene Therapy for Alpha-1 Antitrypsin Deficiency.

    Science.gov (United States)

    Gruntman, Alisha M; Flotte, Terence R

    2017-01-01

    This review seeks to give an overview of alpha-1 antitrypsin deficiency, including the different disease phenotypes that it encompasses. We then describe the different therapeutic endeavors that have been undertaken to address these different phenotypes. Lastly we discuss future potential therapeutics, such as genome editing, and how they may play a role in treating alpha-1 antitrypsin deficiency.

  17. [Vitamin B12 Deficiency in Type 2 Diabetes Mellitus].

    Science.gov (United States)

    Tavares Bello, Carlos; Capitão, Ricardo Miguel; Sequeira Duarte, João; Azinheira, Jorge; Vasconcelos, Carlos

    2017-10-31

    Type 2 diabetes mellitus is a common disease, affecting up to 13.1% of the Portuguese population. In addition to the known micro and macrovascular complications, drug side effects constitute a major concern, leading to changes in the treatment guidelines, which favor safety over efficacy. Metformin is the first-line pharmacological treatment for most patients with type 2 diabetes mellitus; however, it has been associated with vitamin B12 deficiency in up to 30% of treated patients. The authors describe the prevalence of vitamin B12 deficiency in a diabetic population and explore the possible underlying factors. Retrospective, observational study. Clinical and laboratory data of type 2 diabetes mellitus patients whose vitamin B12 status was evaluated in the last decade (2005 - 2016) were analyzed. Patients with known malabsorptive syndromes or having undergone bariatric surgery were excluded from the study. Statistical analysis of the data was done and the results were considered statistically significant at p values 2.2 years and 11 ± 10.4 years of type 2 diabetes mellitus duration. These patients had a high prevalence of complications: diabetic renal disease 47.7%, neuropathy 9.2%, retinopathy 14.9%, coronary artery disease 8.4%, cerebrovascular disease 10.9%, and peripheral arterial disease 5.5%. Vitamin B12 deficiency (21.4% of the population and this subgroup was older (68.4 vs 65.8 years, p = 0.006), had a longer type 2 diabetes mellitus duration (13.35 vs 10.36 years; p = 0.001), higher prevalence of retinopathy (20.9% vs 13.3%; p = 0.005) and thyroid dysfunction (34% vs 23.7%; p = 0.002). Vitamin B12 deficiency was also more frequent in patients treated with metformin (24.7% vs 15.8%; p = 0.017), antiplatelet agents (25.4% vs 16.2%, p 26.8% vs 18.2%; p = 0.001). After adjustment for possible confounders, the variables associated with B12 deficiency were: metformin, hypothyroidism, age and type 2 diabetes mellitus duration. Despite the retrospective design

  18. 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 ...

  19. Hepatic NAD(+) deficiency as a therapeutic target for non-alcoholic fatty liver disease in ageing.

    Science.gov (United States)

    Zhou, Can-Can; Yang, Xi; Hua, Xia; Liu, Jian; Fan, Mao-Bing; Li, Guo-Qiang; Song, Jie; Xu, Tian-Ying; Li, Zhi-Yong; Guan, Yun-Feng; Wang, Pei; Miao, Chao-Yu

    2016-08-01

    Ageing is an important risk factor of non-alcoholic fatty liver disease (NAFLD). Here, we investigated whether the deficiency of nicotinamide adenine dinucleotide (NAD(+) ), a ubiquitous coenzyme, links ageing with NAFLD. Hepatic concentrations of NAD(+) , protein levels of nicotinamide phosphoribosyltransferase (NAMPT) and several other critical enzymes regulating NAD(+) biosynthesis, were compared in middle-aged and aged mice or patients. The influences of NAD(+) decline on the steatosis and steatohepatitis were evaluated in wild-type and H247A dominant-negative, enzymically-inactive NAMPT transgenic mice (DN-NAMPT) given normal or high-fat diet (HFD). Hepatic NAD(+) level decreased in aged mice and humans. NAMPT-controlled NAD(+) salvage, but not de novo biosynthesis pathway, was compromised in liver of elderly mice and humans. Given normal chow, middle-age DN-NAMPT mice displayed systemic NAD(+) reduction and had moderate NAFLD phenotypes, including lipid accumulation, enhanced oxidative stress, triggered inflammation and impaired insulin sensitivity in liver. All these NAFLD phenotypes, especially release of pro-inflammatory factors, Kupffer cell accumulation, monocytes infiltration, NLRP3 inflammasome pathway and hepatic fibrosis (Masson's staining and α-SMA staining), deteriorated further under HFD challenge. Oral administration of nicotinamide riboside, a natural NAD(+) precursor, completely corrected these NAFLD phenotypes induced by NAD(+) deficiency alone or HFD, whereas adenovirus-mediated SIRT1 overexpression only partially rescued these phenotypes. These results provide the first evidence that ageing-associated NAD(+) deficiency is a critical risk factor for NAFLD, and suggest that supplementation with NAD(+) substrates may be a promising therapeutic strategy to prevent and treat NAFLD. © 2016 The British Pharmacological Society.

  20. Vitamin D deficiency and insufficiency among patients with prostate cancer.

    Science.gov (United States)

    Trump, Donald L; Chadha, Manpreet K; Sunga, Annette Y; Fakih, Marwan G; Ashraf, Umeer; Silliman, Carrie G; Hollis, Bruce W; Nesline, Mary K; Tian, Lili; Tan, Wei; Johnson, Candace S

    2009-10-01

    To assess the frequency of vitamin D deficiency among men with prostate cancer, as considerable epidemiological, in vitro, in vivo and clinical data support an association between vitamin D deficiency and prostate cancer outcome. The study included 120 ambulatory men with recurrent prostate cancer and 50 with clinically localized prostate cancer who were evaluated and serum samples assayed for 25-OH vitamin D levels. Then 100 controls (both sexes), matched for age and season of serum sample, were chosen from a prospective serum banking protocol. The relationship between age, body mass index, disease stage, Eastern Cooperative Oncology Group performance status, season and previous therapy on vitamin D status were evaluated using univariate and multivariate analyses. The mean 25-OH vitamin D level was 25.9 ng/mL in those with recurrent disease, 27.5 ng/mL in men with clinically localized prostate cancer and 24.5 ng/mL in controls. The frequency of vitamin D deficiency (<20 ng/mL) and insufficiency (20-31 ng/mL) was 40% and 32% in men with recurrent prostate; 28% had vitamin D levels that were normal (32-100 ng/mL). Among men with localized prostate cancer, 18% were deficient, 50% were insufficient and 32% were normal. Among controls, 31% were deficient, 40% were insufficient and 29% were normal. Metastatic disease (P = 0.005) and season of blood sampling (winter/spring; P = 0.01) were associated with vitamin D deficiency in patients with prostate cancer, while age, race, performance status and body mass index were not. Vitamin D deficiency and insufficiency were common among men with prostate cancer and apparently normal controls in the western New York region.

  1. Prenatal detection of a probable heterozygote for ADA deficiency and severe combined immunodeficiency disease using a microradioassay

    International Nuclear Information System (INIS)

    Aitken, D.A.; Kleijer, W.J.; Niermeijer, M.F.; Galjaard, H.; Herbschleb-Voogt, E.

    1980-01-01

    A pregnancy at risk for adenosine deaminase deficiency and severe combined immunodeficiency disease has been investigated by assay of adenosine deaminase activity in cultured amniotic fluid cells using a microradioassay. A low-normal level of consistent with heterozygote status in the foetus was found and confirmed after birth by assay of red cell and fibroblast adenosine deaminase activities. It is suggested that the radioassay method offers significant advantages in sensitivity and specificity over the standard spectrophotometric procedure. (author)

  2. Clinical significance of enzymatic deficiencies in the gastrointestinal tract with particular reference to lactase deficiency.

    Science.gov (United States)

    Rossi, E; Lentze, M J

    1984-12-01

    The study of deficiencies of small intestinal brush-border hydrolases increased our knowledge about the specific functions of hydrolases in the digestion of smaller molecules on the microvillus surface of the absorptive cells. The sucrase-isomaltase (SI) complex has been shown to be synthesized as a precursor (pro-sucrase-isomaltase) which is then incorporated into the membrane. The hydrophobic N-terminal end of the molecule is anchored in the lipid bilayer. In SI deficiency the molecular base of the disease is still not clear. Absence of SI activity could be due to complete lack of precursor synthesis or to structural changes within the N-terminal end of the SI-complex. Deficiencies of peptide hydrolases have not been reported with the exception of enteropeptidase (EP). Here a congenital deficiency of the enzyme was observed as the primary defect in enzyme synthesis within the enterocytes and as a secondary defect due to exocrine pancreatic insufficiency. In contrast to the primary EP deficiency, the activity of EP can be restored in the cases of exocrine pancreatic insufficiency by treatment with pancreatic extracts. Primary lactase deficiency exists in various forms. Besides congenital lactase deficiency, the late onset or adult type of lactase deficiency has been observed. The latter occurs in many different ethnic groups around the world. Here, using gel electrophoresis and immunoelectrophoresis, the lack of enzyme activity could be shown to be a primary defect in enzyme protein synthesis. In man and in the rat, two different lactases have been identified. In contrast to adult lactase, fetal lactase contains sialic acid at the end of carbohydrate side chains.(ABSTRACT TRUNCATED AT 250 WORDS)

  3. Implications of vitamin D deficiency in lithiasic patient and in general population.

    Science.gov (United States)

    Millán-Rodríguez, F; Gavrilov, P; Gracia-García, S; Angerri-Feu, O; Sánchez-Martín, F M; Villavicencio-Mavrich, H

    2015-05-01

    Vitamin D deficiency causes problems in mineral metabolism but also overall health. In first place a review of the topic was carried out. Then, in order to contextualize it in lithiasic patient, a study on Vitamin D deficiency and its possible relationship with impaired PTH levels is performed. A review of topics such as metabolism, epidemiology and the relationship of vitamin D deficiency with several pathologies was performed. Besides a multivariate analysis and a correlation study between vitamin D and PTH levels was conducted in 100 lithiasic patients. We present a review of Vitamin D metabolism, receptors and functions, as well as about its valuation methodology and the treatment of its deficiency. Lithiasic patients show a higher vitamin D deficiency than general population. Vitamin D deficiency has been significantly associated with increased PTH levels. In addition, there is enough literature showing a relationship between vitamin D deficiency not only with bone disease, but also with multiple diseases. vitamin D levels should be measured in all lithiasic patients, and those with vitamin D deficiency should be treated. Copyright © 2014 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

  4. Biochemical Assessment of Coenzyme Q10 Deficiency

    Directory of Open Access Journals (Sweden)

    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.

  5. Clinical correlates of vitamin D deficiency in established psychosis.

    Science.gov (United States)

    Lally, J; Gardner-Sood, P; Firdosi, M; Iyegbe, C; Stubbs, B; Greenwood, K; Murray, R; Smith, S; Howes, O; Gaughran, F

    2016-03-22

    Suboptimal vitamin D levels have been identified in populations with psychotic disorders. We sought to explore the relationship between vitamin D deficiency, clinical characteristics and cardiovascular disease risk factors among people with established psychosis. Vitamin D levels were measured in 324 community dwelling individuals in England with established psychotic disorders, along with measures of mental health, cardiovascular risk and lifestyle choices. Vitamin D deficiency was defined as serum 25-hydroxyvitamin D (25-OHD) levels below 10 ng/ml (equivalent to Vitamin D as above 30 ng/ml (>50 nmol/L). The mean 25-OHD serum level was 12.4 (SD 7.3) ng/ml, (range 4.0-51.7 ng/ml). Forty nine percent (n = 158) were vitamin D deficient, with only 14 % (n = 45) meeting criteria for sufficiency. Accounting for age, gender, ethnicity and season of sampling, serum 25-OHD levels were negatively correlated with waist circumference (r = -0.220, p vitamin D deficiency. Lower vitamin D levels are associated with increased cardiovascular disease risk factors and in particular metabolic syndrome. Further research is needed to define appropriate protocols for vitamin D testing and supplementation in practice to see if this can improve cardiovascular disease risk. ISRCTN number is ISRCTN58667926 Date of registration: 23/04/2010.

  6. Deficiência de ferro nas afecções gastrointestinais do adulto Iron deficiency related to gastrointestinal diseases in adults

    Directory of Open Access Journals (Sweden)

    Cyrla Zaltman

    2010-06-01

    Full Text Available A anemia por deficiência de ferro (ADF ou a deficiência de ferro (DF isolada são comuns em crianças e mulheres pré-menopausa. Entretanto, em adultos do sexo masculino e mulheres pós-menopausa, essa condição se associa frequentemente a perdas sanguíneas gastrointestinais ou mal absorção. A prevalência das lesões gastrointestinais torna essencial o exame do aparelho digestório superior e inferior através da endoscopia. Investigações complementares devem ser realizadas se os procedimentos endoscópicos não evidenciarem sangramento em situações clínicas, tais como a necessidade de múltiplas hemotransfusões, a ausência de sangramento visível à endoscopia digestiva alta e colonoscopia e a falta de resposta à reposição de ferro.Esses casos devem ser direcionados para investigação do intestino delgado com métodos radiológicos ou, mais recentemente, com a cápsula endoscópica e da enteroscopia com duplo balão. A cintigrafia com hemácias marcadas e a angiografia têm papel restrito, sendo utilizadas apenas no sangramento aberto. O tratamento varia de acordo com a etiologia, a intensidade da perda sanguínea e da deficiência de ferro.Iron deficiency anaemia and isolated iron deficiency are common in children and pre-menopausal women. However, in male adults and post-menopausal women this condition is most frequently caused by gastrointestinal blood loss or malabsorption. The prevalence of gastrointestinal lesions makes the examination by endoscopy of both upper and lower gastrointestinal tracts essential. Further investigations, when the initial exams are negative, are only warranted in cases of multiple transfusions, visible blood loss or lack of response to oral iron supplementation. In these cases examinations should be focused on the small bowel by radiological methods or more recently using capsule endoscopy and double balloon enteroscopy. Nuclear medicine and angiography have a limited role to play in this

  7. 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 ...

  8. Increased Risk for Vitamin D Deficiency in Obese Children with Both Celiac Disease and Type 1 Diabetes

    Directory of Open Access Journals (Sweden)

    Nithya Setty-Shah

    2014-01-01

    Full Text Available Background. It is unknown whether the coexistence of type 1 diabetes (T1D and celiac disease (CD increases the risk for vitamin D deficiency. Aims. To determine the vitamin D status and the risk for vitamin D deficiency in prepubertal children with both T1D and CD compared to controls, TID, and CD. Subjects and Methods. Characteristics of 62 prepubertal children of age 2–13 y with either CD + T1D (n=22, 9.9 ± 3.1 y, CD only (n=18, 8.9 ± 3.3 y, or T1D only (n=22, 10.1 ± 2.8 y were compared to 49 controls of the age of 8.0 ± 2.6 years. Vitamin D deficiency was defined as 25(OHD 85th but 95th percentile. Results. The 4 groups had no difference in 25(OHD (ANOVA P=0.123 before stratification into normal-weight versus overweight/obese subtypes. Following stratification, 25(OHD differed significantly between the subgroups (F(3,98=10.109, ANOVA P<0.001. Post-hoc analysis showed a significantly lower 25(OHD in the overweight/obese CD + T1D compared to the overweight/obese controls (P=0.039 and the overweight/obese CD (P=0.003. Subjects with CD + T1D were 3 times more likely to be vitamin D deficient (OR = 3.1 [0.8–11.9], P=0.098, compared to controls. Conclusions. The coexistence of T1D and CD in overweight/obese prepubertal children may be associated with lower vitamin D concentration.

  9. Biotin deficiency up-regulates TNF-alpha production in murine macrophages.

    Science.gov (United States)

    Kuroishi, Toshinobu; Endo, Yasuo; Muramoto, Koji; Sugawara, Shunji

    2008-04-01

    Biotin, a water-soluble vitamin of the B complex, functions as a cofactor of carboxylases that catalyze an indispensable cellular metabolism. Although significant decreases in serum biotin levels have been reported in patients with chronic inflammatory diseases, the biological roles of biotin in inflammatory responses are unclear. In this study, we investigated the effects of biotin deficiency on TNF-alpha production. Mice were fed a basal diet or a biotin-deficient diet for 8 weeks. Serum biotin levels were significantly lower in biotin-deficient mice than biotin-sufficient mice. After i.v. administration of LPS, serum TNF-alpha levels were significantly higher in biotin-deficient mice than biotin-sufficient mice. A murine macrophage-like cell line, J774.1, was cultured in a biotin-sufficient or -deficient medium for 4 weeks. Cell proliferation and biotinylation of intracellular proteins were decreased significantly in biotin-deficient cells compared with biotin-sufficient cells. Significantly higher production and mRNA expression of TNF-alpha were detected in biotin-deficient J774.1 cells than biotin-sufficient cells in response to LPS and even without LPS stimulation. Intracellular TNF-alpha expression was inhibited by actinomycin D, indicating that biotin deficiency up-regulates TNF-alpha production at the transcriptional level. However, the expression levels of TNF receptors, CD14, and TLR4/myeloid differentiation protein 2 complex were similar between biotin-sufficient and -deficient cells. No differences were detected in the activities of the NF-kappaB family or AP-1. The TNF-alpha induction by biotin deficiency was down-regulated by biotin supplementation in vitro and in vivo. These results indicate that biotin deficiency may up-regulate TNF-alpha production or that biotin excess down-regulates TNF-alpha production, suggesting that biotin status may influence inflammatory diseases.

  10. Treatment of lung disease in alpha-1 antitrypsin deficiency: a systematic review

    Directory of Open Access Journals (Sweden)

    Edgar RG

    2017-05-01

    Full Text Available Ross G Edgar,1,2 Mitesh Patel,3 Susan Bayliss,4 Diana Crossley,2,5 Elizabeth Sapey,2,5 Alice M Turner4,6 1Therapy Services, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK; 2Institute of Inflammation and Ageing, University of Birmingham, Birmingham, UK; 3Division of Primary Care, University of Nottingham, Nottingham, UK; 4Institute of Applied Health Research, University of Birmingham, Birmingham, UK; 5Department of Respiratory Medicine, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK; 6Department of Respiratory Medicine, Heart of England NHS Foundation Trust, Birmingham, UK Background: Alpha-1 antitrypsin deficiency (AATD is a rare genetic condition predisposing individuals to chronic obstructive pulmonary disease (COPD. The treatment is generally extrapolated from COPD unrelated to AATD; however, most COPD trials exclude AATD patients; thus, this study sought to systematically review AATD-specific literature to assist evidence-based patient management.Methods: Standard review methodology was used with meta-analysis and narrative synthesis (PROSPERO-CRD42015019354. Eligible studies were those of any treatment used in severe AATD. Randomized controlled trials (RCTs were the primary focus; however, case series and uncontrolled studies were eligible. All studies had ≥10 participants receiving treatment or usual care, with baseline and follow-up data (>3 months. Risk of bias was assessed appropriately according to study methodology.Results: In all, 7,296 studies were retrieved from searches; 52 trials with 5,632 participants met the inclusion criteria, of which 26 studies involved alpha-1 antitrypsin augmentation and 17 concerned surgical treatments (largely transplantation. Studies were grouped into four management themes: COPD medical, COPD surgical, AATD specific, and other treatments. Computed tomography (CT density, forced expiratory volume in 1 s, diffusing capacity of the lungs for carbon monoxide

  11. 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.

  12. Anti-thrombin III, Protein C, and Protein S deficiency in acute coronary syndrome

    Directory of Open Access Journals (Sweden)

    Dasnan Ismail

    2002-06-01

    Full Text Available The final most common pathway for the majority of coronary artery disease is occlusion of a coronary vessel. Under normal conditions, antithrombin III (AT III, protein C, and protein S as an active protein C cofactor, are natural anticoagulants (hemostatic control that balances procoagulant activity (thrombin antithrombin complex balance to prevent thrombosis. If the condition becomes unbalanced, natural anticoagulants and the procoagulants can lead to thrombosis. Thirty subjects with acute coronary syndrome (ACS were studied for the incidence of antithrombin III (AT III, protein C, and protein S deficiencies, and the result were compare to the control group. Among patients with ACS, the frequency of distribution of AT-III with activity < 75% were 23,3% (7 of 30, and only 6,7% ( 2 of 30 in control subject. No one of the 30 control subject have protein C activity deficient, in ACS with activity < 70% were 13,3% (4 of 30. Fifteen out of the 30 (50% control subjects had protein S activity deficiency, while protein S deficiency activity < 70% was found 73.3.% (22 out of 30. On linear regression, the deterministic coefficient of AT-III activity deficiency to the development ACS was 13,25 %, and the deterministic coefficient of protein C activity deficient to the development of ACS was 9,06 %. The cut-off point for AT-III without protein S deficiency expected to contribute to the development of vessel disease was 45%. On discriminant analysis, protein C activity deficiency posed a risk for ACS of 4,5 greater than non deficient subjects, and AT-III activity deficiency posed a risk for ACS of 3,5 times greater than non deficient subjects. On binary logistic regression, protein S activity acted only as a reinforcing factor of AT-III activity deficiency in the development of ACS. Protein C and AT III deficiency can trigger ACS, with determinant coefficients of 9,06% and 13,25% respectively. Low levels of protein C posed a greater risk of

  13. Biopterin-deficient hyperphenylalaninemia: Diagnosis and treatment

    Directory of Open Access Journals (Sweden)

    E. A. Nikolaeva

    2015-01-01

    Full Text Available The term phenylketonuria encompasses some genetically heterogeneous diseases from a group of hereditary amino acid metabolic disorders, the key biochemical sign of which is a steady increase in blood phenylalanine levels – hyperphenylalaninemia. Phenylketonuria is a most common disease of the above group; its rate in the Russian Federation is 1:7140 neonates. The rare causes of hyperphenylalaninemia include the cofactor (biopterin-deficient forms associated with tetrahydrobiopterin deficiency, leading to the blocked metabolic pathways for converting phenylalanine to tyrosine and for synthesizing catecholamine and serotonin precursors (L-dopa and 5-hydroxytryptophan. The distinguishing feature of all cofactor forms of hyperphenylalaninemia is the inefficiency of an isolated low-protein diet. Cofactor therapy with sapropterin in combination with correction of neuromediatory disorders is used in the combination treatment of these patients. The paper presents a case history of a child with severe biopterin-deficient hyperphenylalaninemia resulting from a defect in the PTS gene. The clinical example illustrates difficulties associated with the diagnosis of cofactor hyperphenylalaninemia and with long individual dosage adjustments for medications. 

  14. Vitamin D Deficiency in Patients with Systemic Lupus Erythematosus

    Directory of Open Access Journals (Sweden)

    Suzan M. Attar

    2013-01-01

    Full Text Available Objectives: Hypovitaminosis D is common in the general population. Many studies that have been conducted to show the association between vitamin D deficiency and systemic lupus erythematosus (SLE reveal that deficiencies in vitamin D are common in this group of patients. Our aim was to study the relationship between 25(OHD and disease activity in patients with SLE.Methods: Retrospective cohort study of patients with SLE who were followed up at King Abdulaziz University Hospital, Jeddah, from January 2007 to November 2010. Demographic and clinical data were recorded and the 25(OHD levels of the patients were measured. Chi square tests, Student’s t-test, ANOVA and Pearson tests were used for data analysis. ANOVA test was followed by Bonferroni correction. A p-value <0.05 was considered significant.Results: Ninety-five patients with SLE were enrolled in the study. The levels of 25(OHD were significantly lower in patients with active SLE (n=41; 43% than in those with inactive disease (n=54; 57%; p=0.04. The mean (SD levels were 22.3 (14 nmol/L for patients with active disease against 25.0 (14 nmol/L for patients with inactive SLE. No correlation was detected between 25(OH D levels and disease activity score evaluated by SLEDAI-2K. By Pearson correlation, a significant negative correlation existed between 25(OH D and anti ds-DNA (r=-0.38; p<0.001; a positive correlation existed between 25(OHD levels and C4 (r=0.25; p=0.25. By chi square testing, azathioprine treatment (OR=3.5, low C4 (OR= 2.23, low C3 (OR=1.92, and active disease (OR=1.6 were associated with 25(OHD deficiency in SLE patients.Conclusion: Vitamin D deficiency is frequent in patients with SLE. Patients with SLE have a higher risk of developing 25(OHD deficiency in the presence of low serum C3 and C4 levels, and high anti-dsDNA levels.

  15. Ligneous Periodontitis in a Child with Plasminogen Deficiency ...

    African Journals Online (AJOL)

    Ligneous periodontitis (LP), a rare periodontal disease, is seen secondary to plasminogen deficiency and fibrin deposition. It is characterized by nodular gingival enlargements and progressive destructive membranous periodontal disease. It generally ends with the early loss of teeth. Defective fibrinolysis and abnormal ...

  16. 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 ...

  17. Diagnosis and treatment of unexplained anemia with iron deficiency without overt bleeding

    DEFF Research Database (Denmark)

    Dahlerup, Jens Frederik; Eivindson, Martin; Jacobsen, Bent Ascanius

    2015-01-01

    A general overview is given of the causes of anemia with iron deficiency as well as the pathogenesis of anemia and the para-clinical diagnosis of anemia. Anemia with iron deficiency but without overt GI bleeding is associated with a risk of malignant disease of the gastrointestinal tract; upper...... gastrointestinal cancer is 1/7 as common as colon cancer. Benign gastrointestinal causes of anemia are iron malabsorption (atrophic gastritis, celiac disease, chronic inflammation, and bariatric surgery) and chronic blood loss due to gastrointestinal ulcerations. The following diagnostic strategy is recommended...... for unexplained anemia with iron deficiency: conduct serological celiac disease screening with transglutaminase antibody (IgA type) and IgA testing and perform bidirectional endoscopy (gastroscopy and colonoscopy). Bidirectional endoscopy is not required in premenopausal women

  18. Hepatic NAD+ deficiency as a therapeutic target for non‐alcoholic fatty liver disease in ageing

    Science.gov (United States)

    Zhou, Can‐Can; Yang, Xi; Hua, Xia; Liu, Jian; Fan, Mao‐Bing; Li, Guo‐Qiang; Song, Jie; Xu, Tian‐Ying; Li, Zhi‐Yong; Guan, Yun‐Feng

    2016-01-01

    Abstract Background and Purpose Ageing is an important risk factor of non‐alcoholic fatty liver disease (NAFLD). Here, we investigated whether the deficiency of nicotinamide adenine dinucleotide (NAD+), a ubiquitous coenzyme, links ageing with NAFLD. Experimental Approach Hepatic concentrations of NAD+, protein levels of nicotinamide phosphoribosyltransferase (NAMPT) and several other critical enzymes regulating NAD+ biosynthesis, were compared in middle‐aged and aged mice or patients. The influences of NAD+ decline on the steatosis and steatohepatitis were evaluated in wild‐type and H247A dominant‐negative, enzymically‐inactive NAMPT transgenic mice (DN‐NAMPT) given normal or high‐fat diet (HFD). Key Results Hepatic NAD+ level decreased in aged mice and humans. NAMPT‐controlled NAD+ salvage, but not de novo biosynthesis pathway, was compromised in liver of elderly mice and humans. Given normal chow, middle‐age DN‐NAMPT mice displayed systemic NAD+ reduction and had moderate NAFLD phenotypes, including lipid accumulation, enhanced oxidative stress, triggered inflammation and impaired insulin sensitivity in liver. All these NAFLD phenotypes, especially release of pro‐inflammatory factors, Kupffer cell accumulation, monocytes infiltration, NLRP3 inflammasome pathway and hepatic fibrosis (Masson's staining and α‐SMA staining), deteriorated further under HFD challenge. Oral administration of nicotinamide riboside, a natural NAD+ precursor, completely corrected these NAFLD phenotypes induced by NAD+ deficiency alone or HFD, whereas adenovirus‐mediated SIRT1 overexpression only partially rescued these phenotypes. Conclusions and Implications These results provide the first evidence that ageing‐associated NAD+ deficiency is a critical risk factor for NAFLD, and suggest that supplementation with NAD+ substrates may be a promising therapeutic strategy to prevent and treat NAFLD. PMID:27174364

  19. Acid Lipase Disease

    Science.gov (United States)

    ... of Neurological Disorders and Stroke conducts and supports research to understand lipid storage diseases such as acid lipase deficiency and ... of Neurological Disorders and Stroke conducts and supports research to understand lipid storage diseases such as acid lipase deficiency and ...

  20. 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.

  1. Ligneous Periodontitis in a Child with Plasminogen Deficiency

    African Journals Online (AJOL)

    2018-01-30

    Jan 30, 2018 ... Ligneous periodontitis (LP), a rare periodontal disease, is seen secondary to plasminogen deficiency and fibrin deposition. It is characterized by nodular gingival enlargements and progressive destructive membranous periodontal disease. It generally ends with the early loss of teeth. Defective fibrinolysis ...

  2. Modeling Late-Onset Sporadic Alzheimer’s Disease through BMI1 Deficiency

    Directory of Open Access Journals (Sweden)

    Anthony Flamier

    2018-05-01

    Full Text Available Late-onset sporadic Alzheimer’s disease (AD is the most prevalent form of dementia, but its origin remains poorly understood. The Bmi1/Ring1 protein complex maintains transcriptional repression of developmental genes through histone H2A mono-ubiquitination, and Bmi1 deficiency in mice results in growth retardation, progeria, and neurodegeneration. Here, we demonstrate that BMI1 is silenced in AD brains, but not in those with early-onset familial AD, frontotemporal dementia, or Lewy body dementia. BMI1 expression was also reduced in cortical neurons from AD patient-derived induced pluripotent stem cells but not in neurons overexpressing mutant APP and PSEN1. BMI1 knockout in human post-mitotic neurons resulted in amyloid beta peptide secretion and deposition, p-Tau accumulation, and neurodegeneration. Mechanistically, BMI1 was required to repress microtubule associated protein tau (MAPT transcription and prevent GSK3beta and p53 stabilization, which otherwise resulted in neurodegeneration. Restoration of BMI1 activity through genetic or pharmaceutical approaches could represent a therapeutic strategy against AD.

  3. The role of proteases, endoplasmic reticulum stress and SERPINA1 heterozygosity in lung disease and alpha-1 anti-trypsin deficiency.

    LENUS (Irish Health Repository)

    Greene, Catherine M

    2012-02-01

    The serine proteinase inhibitor alpha-1 anti-trypsin (AAT) provides an antiprotease protective screen throughout the body. Mutations in the AAT gene (SERPINA1) that lead to deficiency in AAT are associated with chronic obstructive pulmonary diseases. The Z mutation encodes a misfolded variant of AAT that is not secreted effectively and accumulates intracellularly in the endoplasmic reticulum of hepatocytes and other AAT-producing cells. Until recently, it was thought that loss of antiprotease function was the major cause of ZAAT-related lung disease. However, the contribution of gain-of-function effects is now being recognized. Here we describe how both loss- and gain-of-function effects can contribute to ZAAT-related lung disease. In addition, we explore how SERPINA1 heterozygosity could contribute to smoking-induced chronic obstructive pulmonary diseases and consider the consequences.

  4. Iron deficiency and neurologic disease in children | Chiabi | Clinics ...

    African Journals Online (AJOL)

    Iron deficiency is a frequent disorder and a public health problem especially in children and pregnant women. The clinical manifestations are varied, and the most dreaded are neurologic. These neurologic manifestations are often missed as differential diagnosis in current clinical practice. The authors review iron ...

  5. Lysosomal storage diseases

    Science.gov (United States)

    Ferreira, Carlos R.; Gahl, William A.

    2016-01-01

    Lysosomes are cytoplasmic organelles that contain a variety of different hydrolases. A genetic deficiency in the enzymatic activity of one of these hydrolases will lead to the accumulation of the material meant for lysosomal degradation. Examples include glycogen in the case of Pompe disease, glycosaminoglycans in the case of the mucopolysaccharidoses, glycoproteins in the cases of the oligosaccharidoses, and sphingolipids in the cases of Niemann-Pick disease types A and B, Gaucher disease, Tay-Sachs disease, Krabbe disease, and metachromatic leukodystrophy. Sometimes, the lysosomal storage can be caused not by the enzymatic deficiency of one of the hydrolases, but by the deficiency of an activator protein, as occurs in the AB variant of GM2 gangliosidosis. Still other times, the accumulated lysosomal material results from failed egress of a small molecule as a consequence of a deficient transporter, as in cystinosis or Salla disease. In the last couple of decades, enzyme replacement therapy has become available for a number of lysosomal storage diseases. Examples include imiglucerase, taliglucerase and velaglucerase for Gaucher disease, laronidase for Hurler disease, idursulfase for Hunter disease, elosulfase for Morquio disease, galsulfase for Maroteaux-Lamy disease, alglucosidase alfa for Pompe disease, and agalsidase alfa and beta for Fabry disease. In addition, substrate reduction therapy has been approved for certain disorders, such as eliglustat for Gaucher disease. The advent of treatment options for some of these disorders has led to newborn screening pilot studies, and ultimately to the addition of Pompe disease and Hurler disease to the Recommended Uniform Screening Panel (RUSP) in 2015 and 2016, respectively. PMID:29152458

  6. Genetics Home Reference: ornithine transcarbamylase deficiency

    Science.gov (United States)

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

  7. Hematopoietic Sphingosine 1-Phosphate Lyase Deficiency Decreases Atherosclerotic Lesion Development in LDL-Receptor Deficient Mice

    NARCIS (Netherlands)

    Bot, Martine; Van Veldhoven, Paul P.; de Jager, Saskia C. A.; Johnson, Jason; Nijstad, Niels; Van Santbrink, Peter J.; Westra, Marijke M.; Van Der Hoeven, Gerd; Gijbels, Marion J.; Mueller-Tidow, Carsten; Varga, Georg; Tietge, Uwe J. F.; Kuiper, Johan; Van Berkel, Theo J. C.; Nofer, Jerzy-Roch; Bot, Ilze; Biessen, Erik A. L.

    2013-01-01

    Aims: Altered sphingosine 1-phosphate (S1P) homeostasis and signaling is implicated in various inflammatory diseases including atherosclerosis. As S1P levels are tightly controlled by S1P lyase, we investigated the impact of hematopoietic S1P lyase (Sgpl1(-/-)) deficiency on leukocyte subsets

  8. Hematopoietic sphingosine 1-phosphate lyase deficiency decreases atherosclerotic lesion development in LDL-receptor deficient mice

    NARCIS (Netherlands)

    Bot, Martine; van Veldhoven, Paul P.; de Jager, Saskia C. A.; Johnson, Jason; Nijstad, Niels; van Santbrink, Peter J.; Westra, Marijke M.; van der Hoeven, Gerd; Gijbels, Marion J.; Müller-Tidow, Carsten; Varga, Georg; Tietge, Uwe J. F.; Kuiper, Johan; van Berkel, Theo J. C.; Nofer, Jerzy-Roch; Bot, Ilze; Biessen, Erik A. L.

    2013-01-01

    Altered sphingosine 1-phosphate (S1P) homeostasis and signaling is implicated in various inflammatory diseases including atherosclerosis. As S1P levels are tightly controlled by S1P lyase, we investigated the impact of hematopoietic S1P lyase (Sgpl1(-/-)) deficiency on leukocyte subsets relevant to

  9. First Occurrence of Plasmablastic Lymphoma in Adenosine Deaminase-Deficient Severe Combined Immunodeficiency Disease Patient and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Maddalena Migliavacca

    2018-02-01

    Full Text Available Adenosine deaminase-deficient severe combined immunodeficiency disease (ADA-SCID is a primary immune deficiency characterized by mutations in the ADA gene resulting in accumulation of toxic compounds affecting multiple districts. Hematopoietic stem cell transplantation (HSCT from a matched donor and hematopoietic stem cell gene therapy are the preferred options for definitive treatment. Enzyme replacement therapy (ERT is used to manage the disease in the short term, while a decreased efficacy is reported in the medium-long term. To date, eight cases of lymphomas have been described in ADA-SCID patients. Here we report the first case of plasmablastic lymphoma occurring in a young adult with ADA-SCID on long-term ERT, which turned out to be Epstein–Barr virus associated. The patient previously received infusions of genetically modified T cells. A cumulative analysis of the eight published cases of lymphoma from 1992 to date, and the case here described, reveals a high mortality (89%. The most common form is diffuse large B-cell lymphoma, which predominantly occurs in extra nodal sites. Seven cases occurred in patients on ERT and two after haploidentical HSCT. The significant incidence of immunodeficiency-associated lymphoproliferative disorders and poor survival of patients developing this complication highlight the priority in finding a prompt curative treatment for ADA-SCID.

  10. Does taurine deficiency cause metabolic bone disease and rickets in polar bear cubs raised in captivity?

    Science.gov (United States)

    Chesney, Russell W; Hedberg, Gail E; Rogers, Quinton R; Dierenfeld, Ellen S; Hollis, Bruce E; Derocher, Andrew; Andersen, Magnus

    2009-01-01

    Rickets and fractures have been reported in captive polar bears. Taurine (TAU) is key for the conjugation of ursodeoxycholic acid (UDCA), a bile acid unique to bears. Since TAU-conjugated UDCA optimizes fat and fat-soluble vitamin absorption, we asked if TAU deficiency could cause vitamin D malabsorption and lead to metabolic bone disease in captive polar bears. We measured TAU levels in plasma (P) and whole blood (WB) from captive and free-ranging cubs and adults, and vitamin D3 and TAU concentrations in milk samples from lactating sows. Plasma and WB TAU levels were significantly higher in cubs vs captive and free-ranging adult bears. Vitamin D in polar bear milk was 649.2 +/- 569.2 IU/L, similar to that found in formula. The amount of TAU in polar bear milk is 3166.4 +/- 771 nmol/ml, 26-fold higher than in formula. Levels of vitamin D in bear milk and formula as well as in plasma do not indicate classical nutritional vitamin D deficiency. Higher dietary intake of TAU by free-ranging cubs may influence bile acid conjugation and improve vitamin D absorption.

  11. Factor VII Deficiency: Clinical Phenotype, Genotype and Therapy.

    Science.gov (United States)

    Napolitano, Mariasanta; Siragusa, Sergio; Mariani, Guglielmo

    2017-03-28

    Factor VII deficiency is the most common among rare inherited autosomal recessive bleeding disorders, and is a chameleon disease due to the lack of a direct correlation between plasma levels of coagulation Factor VII and bleeding manifestations. Clinical phenotypes range from asymptomatic condition-even in homozygous subjects-to severe life-threatening bleedings (central nervous system, gastrointestinal bleeding). Prediction of bleeding risk is thus based on multiple parameters that challenge disease management. Spontaneous or surgical bleedings require accurate treatment schedules, and patients at high risk of severe hemorrhages may need prophylaxis from childhood onwards. The aim of the current review is to depict an updated summary of clinical phenotype, laboratory diagnosis, and treatment of inherited Factor VII deficiency.

  12. Hematopoietic Sphingosine 1-Phosphate Lyase Deficiency Decreases Atherosclerotic Lesion Development in LDL-Receptor Deficient Mice

    NARCIS (Netherlands)

    Bot, M.; Veldhoven, van P.P.; Jager, de S.C.; Johnson, J.; Nijstad, N.; van, Santbrink P.J.; Westra, M.M.; Hoeven, van der G.; Gijbels, M.J.; Muller-Tidow, C.; Varga, G.; Tietge, U.J.; Kuiper, J.; Berkel, van T.J.; Nofer, J.R.; Bot, I.; Biessen, E.A.

    2013-01-01

    Abstract Aims Altered sphingosine 1-phosphate (S1P) homeostasis and signaling is implicated in various inflammatory diseases including atherosclerosis. As S1P levels are tightly controlled by S1P lyase, we investigated the impact of hematopoietic S1P lyase (Sgpl1−/−) deficiency on leukocyte

  13. Genetics Home Reference: dopamine beta-hydroxylase deficiency

    Science.gov (United States)

    ... common features include an unusually large range of joint movement (hypermobility) and muscle weakness. Related Information What ... Dopamine beta-hydroxylase deficiency Washington Univeristy, St. Louis: Neuromuscular Disease Center Patient Support and Advocacy Resources (1 ...

  14. [Vitamin D levels in ankylosing spondylitis: does deficiency correspond to disease activity?].

    Science.gov (United States)

    Pokhai, Gabriel G; Bandagi, Sabiha; Abrudescu, Adriana

    2014-01-01

    Ankylosing spondylitis (AS) is an inflammatory disorder that presents with arthritis of the axial skeleton, including sacroiliac joints. Vitamin D is a secosteroid hormone with a long-established role in calcium and phosphate homeostasis, and in the regulation of bone formation and resorption. It is now known that vitamin D plays an immunosuppressive role in the body, and there is interest of late in the role of vitamin D in autoimmune diseases. Inflammation may be responsible for some of the loss of bone mineral density seen in AS. We reviewed the literature for studies assessing vitamin D level as a marker of AS disease activity and those examining vitamin D levels in AS in comparison to healthy controls. Four of 7 studies found a significant negative correlation between vitamin D levels and Bath Ankylosing Spondylitis Index (BASDAI), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). In a review of 8 case-control studies, the mean level of 25-hydroxyvitamin D3 was 22.8 ± 14.1 ng/mL in 555 AS patients versus 26.6 ± 12.5 ng/mL in 557 healthy controls. When compared with a 2-sample t test, vitamin D levels were significantly higher in healthy controls (p < 0.01). We conclude that patients with AS appear to have lower vitamin D levels versus healthy controls; however, the cause is unclear. Existing studies do not demonstrate a consistent link between vitamin D levels and disease activity in AS. Further studies are in need to determine if a causative link exists between vitamin D deficiency and AS. Copyright © 2014 Elsevier Editora Ltda. All rights reserved.

  15. Co-existence of classic familial lecithin-cholesterol acyl transferase deficiency and fish eye disease in the same family

    Directory of Open Access Journals (Sweden)

    H S Mahapatra

    2015-01-01

    Full Text Available We report a family with a rare genetic disorder arising out of mutation in the gene that encodes for the enzyme lecithin-cholesterol acyltransferase (LCAT. The proband presented with nephrotic syndrome, hemolytic anemia, cloudy cornea, and dyslipidemia. Kidney biopsy showed certain characteristic features to suggest LCAT deficiency, and the enzyme activity in the serum was undetectable. Mother and younger sister showed corneal opacity and dyslipidemia but no renal or hematological involvement. These two members had a milder manifestation of the disease called fish eye disease. This case is presented to emphasize the importance of taking family history and doing a good clinical examination in patients with nephrotic syndrome and carefully analyze the lipid fractions in these subset of patients.

  16. Is Vitamin D Deficiency a Confounder in Alcoholic Skeletal Muscle Myopathy?

    NARCIS (Netherlands)

    Wijnia, J.W.; Wielders, J.P.M.; Lips, P.T.A.M.; van der Wiel, A.; Mulder, C.L.; Nieuwenhuis, K.G.A.

    2013-01-01

    Background: Excessive intake of alcohol is often associated with low or subnormal levels of vitamin D even in the absence of active liver disease. As vitamin D deficiency is a well-recognized cause of myopathy, alcoholic myopathy might be related to vitamin D deficiency. Chronic alcoholic myopathy

  17. 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.

  18. 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...

  19. Increased Laforin and Laforin Binding to Glycogen Underlie Lafora Body Formation in Malin-deficient Lafora Disease*

    Science.gov (United States)

    Tiberia, Erica; Turnbull, Julie; Wang, Tony; Ruggieri, Alessandra; Zhao, Xiao-Chu; Pencea, Nela; Israelian, Johan; Wang, Yin; Ackerley, Cameron A.; Wang, Peixiang; Liu, Yan; Minassian, Berge A.

    2012-01-01

    The solubility of glycogen, essential to its metabolism, is a property of its shape, a sphere generated through extensive branching during synthesis. Lafora disease (LD) is a severe teenage-onset neurodegenerative epilepsy and results from multiorgan accumulations, termed Lafora bodies (LB), of abnormally structured aggregation-prone and digestion-resistant glycogen. LD is caused by loss-of-function mutations in the EPM2A or EPM2B gene, encoding the interacting laforin phosphatase and malin E3 ubiquitin ligase enzymes, respectively. The substrate and function of malin are unknown; an early counterintuitive observation in cell culture experiments that it targets laforin to proteasomal degradation was not pursued until now. The substrate and function of laforin have recently been elucidated. Laforin dephosphorylates glycogen during synthesis, without which phosphate ions interfere with and distort glycogen construction, leading to LB. We hypothesized that laforin in excess or not removed following its action on glycogen also interferes with glycogen formation. We show in malin-deficient mice that the absence of malin results in massively increased laforin preceding the appearance of LB and that laforin gradually accumulates in glycogen, which corresponds to progressive LB generation. We show that increasing the amounts of laforin in cell culture causes LB formation and that this occurs only with glycogen binding-competent laforin. In summary, malin deficiency causes increased laforin, increased laforin binding to glycogen, and LB formation. Furthermore, increased levels of laforin, when it can bind glycogen, causes LB. We conclude that malin functions to regulate laforin and that malin deficiency at least in part causes LB and LD through increased laforin binding to glycogen. PMID:22669944

  20. Vitamin A deficiency and Newcastle disease virus infection in chickens : a model for the study of measles infection in vitamin A-deficient children

    NARCIS (Netherlands)

    Sijtsma, S.R.

    1989-01-01

    Vitamin A deficiency is one of the most important micronutrient deficiencies in developing countries and usually does not occur as an isolated problem but is almost invariably accompanied by protein-energy malnutrition. Xerophthalmia, the term used for all ocular manifestations of impaired vitamin A

  1. Predictors of Vitamin D Deficiency in Predialysis Patients with Stage ...

    African Journals Online (AJOL)

    Objective: Vitamin D status and risk factors of Vitamin D deficiency in chronic kidney disease (CKD) patients in China have been seldom reported before. In this study, we aim to investigate serum 25‑hydroxyvitamin D [25(OH)D] status and find the predictors of Vitamin D deficiency in predialysis patients with Stage 3–5 CKDs ...

  2. Structural and Genetic Studies Demonstrate Neurologic Dysfunction in Triosephosphate Isomerase Deficiency Is Associated with Impaired Synaptic Vesicle Dynamics

    Energy Technology Data Exchange (ETDEWEB)

    Roland, Bartholomew P.; Zeccola, Alison M.; Larsen, Samantha B.; Amrich, Christopher G.; Talsma, Aaron D.; Stuchul, Kimberly A.; Heroux, Annie; Levitan, Edwin S.; VanDemark, Andrew P.; Palladino, Michael J.; Pallanck, Leo J.

    2016-03-31

    Triosephosphate isomerase (TPI) deficiency is a poorly understood disease characterized by hemolytic anemia, cardiomyopathy, neurologic dysfunction, and early death. TPI deficiency is one of a group of diseases known as glycolytic enzymopathies, but is unique for its severe patient neuropathology and early mortality. The disease is caused by missense mutations and dysfunction in the glycolytic enzyme, TPI. Previous studies have detailed structural and catalytic changes elicited by disease-associated TPI substitutions, and samples of patient erythrocytes have yielded insight into patient hemolytic anemia; however, the neuropathophysiology of this disease remains a mystery. This study combines structural, biochemical, and genetic approaches to demonstrate that perturbations of the TPI dimer interface are sufficient to elicit TPI deficiency neuropathogenesis. The present study demonstrates that neurologic dysfunction resulting from TPI deficiency is characterized by synaptic vesicle dysfunction, and can be attenuated with catalytically inactive TPI. Collectively, our findings are the first to identify, to our knowledge, a functional synaptic defect in TPI deficiency derived from molecular changes in the TPI dimer interface.

  3. 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 ...

  4. Developmental vitamin D deficiency causes abnormal brain development.

    Science.gov (United States)

    Eyles, D W; Feron, F; Cui, X; Kesby, J P; Harms, L H; Ko, P; McGrath, J J; Burne, T H J

    2009-12-01

    There is now clear evidence that vitamin D is involved in brain development. Our group is interested in environmental factors that shape brain development and how this may be relevant to neuropsychiatric diseases including schizophrenia. The origins of schizophrenia are considered developmental. We hypothesised that developmental vitamin D (DVD) deficiency may be the plausible neurobiological explanation for several important epidemiological correlates of schizophrenia namely: (1) the excess winter/spring birth rate, (2) increased incidence of the disease in 2nd generation Afro-Caribbean migrants and (3) increased urban birth rate. Moreover we have published two pieces of direct epidemiological support for this hypothesis in patients. In order to establish the "Biological Plausibility" of this hypothesis we have developed an animal model to study the effect of DVD deficiency on brain development. We do this by removing vitamin D from the diet of female rats prior to breeding. At birth we return all dams to a vitamin D containing diet. Using this procedure we impose a transient, gestational vitamin D deficiency, while maintaining normal calcium levels throughout. The brains of offspring from DVD-deficient dams are characterised by (1) a mild distortion in brain shape, (2) increased lateral ventricle volumes, (3) reduced differentiation and (4) diminished expression of neurotrophic factors. As adults, the alterations in ventricular volume persist and alterations in brain gene and protein expression emerge. Adult DVD-deficient rats also display behavioural sensitivity to agents that induce psychosis (the NMDA antagonist MK-801) and have impairments in attentional processing. In this review we summarise the literature addressing the function of vitamin D on neuronal and non-neuronal cells as well as in vivo results from DVD-deficient animals. Our conclusions from these data are that vitamin D is a plausible biological risk factor for neuropsychiatric disorders and that

  5. Novel targets for ATM-deficient malignancies

    Science.gov (United States)

    Winkler, Johannes; Hofmann, Kay; Chen, Shuhua

    2014-01-01

    Conventional chemo- and radiotherapies for the treatment of cancer target rapidly dividing cells in both tumor and non-tumor tissues and can exhibit severe cytotoxicity in normal tissue and impair the patient's immune system. Novel targeted strategies aim for higher efficacy and tumor specificity. The role of ATM protein in the DNA damage response is well known and ATM deficiency frequently plays a role in tumorigenesis and development of malignancy. In addition to contributing to disease development, ATM deficiency also renders malignant cells heavily dependent on other pathways that cooperate with the ATM-mediated DNA damage response to ensure tumor cell survival. Disturbing those cooperative pathways by inhibiting critical protein components allows specific targeting of tumors while sparing healthy cells with normal ATM status. We review druggable candidate targets for the treatment of ATM-deficient malignancies and the mechanisms underlying such targeted therapies. PMID:27308314

  6. High Frequency of Symptomatic Zinc Deficiency in Infants in Northern Ethiopia

    Directory of Open Access Journals (Sweden)

    Federica Dassoni

    2014-01-01

    Full Text Available Background. Zinc deficiency occurs in infants when its demand exceeds its supply. It presents with cutaneous signs which, in severe cases, are associated with diarrhea, alopecia, and irritability. Genetic and acquired forms of zinc deficiency have been reported and often overlap clinical features. Malnutrition, prematurity, malabsorption syndromes, and burns may cause an increased demand for zinc. Methods. Cases of acquired transient infantile zinc deficiency (TIZD observed during a period of 3 years at Ayder Referral Hospital of Mekelle, Northern Ethiopia, are reported here. Since no sophisticated tests were available at our center, the diagnosis was based on the clinical signs and prompt response to oral zinc supplementation. Results. We observed 18 cases of TIZD at our center. All patients were full-term and breastfeeding infants with no relevant associated diseases. Conclusions. In this region, a high incidence of this condition is observed. We could not rule out whether heterozygosity for the genetic mutation was present or that the disease was caused by a nutritional deficiency in the mothers or more probably because both the factors coexisted together. However, further studies are necessary to better understand the causes of the increased incidence of this disease in Northern Ethiopia.

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

    Science.gov (United States)

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

    2018-02-01

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

  8. Is zinc deficiency a risk factor for atherosclerosis?

    Science.gov (United States)

    Beattie, John H; Kwun, In-Sook

    2004-02-01

    The development of atherosclerosis is influenced by genetic, lifestyle and nutritional risk factors. Zn and metallothionein deficiency can enhance oxidative-stress-related signalling processes in endothelial cells, and since changes in available plasma Zn may affect the Zn status of the endothelium, Zn deficiency could be a risk factor for IHD. Although the association of Zn with many proteins is essential for their function, three key signalling processes are highlighted as being principal targets for the effect of Zn deficiency: the activation of NF-kappaB, the activation of caspase enzymes and the signalling of NO. The need to develop a reliable indicator of Zn status is critical to any epidemiological approach for studying the relationship between Zn status and disease incidence. Studies using appropriate animal models and investigating how the plasma Zn pool influences endothelial intracellular labile Zn would be helpful in appreciating the importance of Zn deficiency in atherogenesis.

  9. Thyroid disorders in mild iodine deficiency.

    Science.gov (United States)

    Laurberg, P; Nøhr, S B; Pedersen, K M; Hreidarsson, A B; Andersen, S; Bülow Pedersen, I; Knudsen, N; Perrild, H; Jørgensen, T; Ovesen, L

    2000-11-01

    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 in elderly subjects, especially women, with risk of cardiac arrhythmias, osteoporosis, and muscle wasting. The hyperthyroidism is caused by autonomous nodular growth and function of the thyroid gland and it is accompanied by a high frequency of goiter. Pregnant women and small children are not immediately 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 disorders are avoided but not higher. Iodine supplementation programs should aim at relatively uniform iodine intake, avoiding deficient or excessive iodine intake in subpopulations. To adopt such a strategy, surveillance programs are needed.

  10. Genetics Home Reference: adenosine deaminase deficiency

    Science.gov (United States)

    ... Combined Immunodeficiency (SCID) and Conditions Associated with T Cell Lymphoneia (PDF) Genetic Testing (1 link) Genetic Testing Registry: Severe ... Diseases Immune Deficiency Foundation Jeffrey Modell Foundation National Organization for Rare ... OMIM (1 link) SEVERE COMBINED IMMUNODEFICIENCY, AUTOSOMAL RECESSIVE, T CELL-NEGATIVE, B CELL-NEGATIVE, NK CELL-NEGATIVE, DUE ...

  11. 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 ...

  12. 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...

  13. Deficient Rab11 activity underlies glucose hypometabolism in primary neurons of Huntington’s disease mice

    International Nuclear Information System (INIS)

    Li, Xueyi; Valencia, Antonio; McClory, Hollis; Sapp, Ellen; Kegel, Kimberly B.; DiFiglia, Marian

    2012-01-01

    Highlights: ► Primary Huntington’s disease neurons are impaired in taking up glucose. ► Rab11 modulates glucose uptake in neurons. ► Increasing Rab11 activity attenuates the glucose uptake defect in disease neurons. ► We provide a novel mechanism for glucose hypometabolism in Huntington’s disease. -- Abstract: Huntington’s disease (HD) is a progressive neurodegenerative disorder caused by a CAG repeat expansion in the huntingtin gene. Positron emission tomography studies have revealed a decline in glucose metabolism in the brain of patients with HD by a mechanism that has not been established. We examined glucose utilization in embryonic primary cortical neurons of wild-type (WT) and HD knock-in mice, which have 140 CAG repeats inserted in the endogenous mouse huntingtin gene (HD 140Q/140Q ). Primary HD 140Q/140Q cortical neurons took up significantly less glucose than did WT neurons. Expression of permanently inactive and permanently active forms of Rab11 correspondingly altered glucose uptake in WT neurons, suggesting that normal activity of Rab11 is needed for neuronal uptake of glucose. It is known that Rab11 activity is diminished in HD 140Q/140Q neurons. Expression of dominant active Rab11 to enhance the activity of Rab11 normalized glucose uptake in HD 140Q/140Q neurons. These results suggest that deficient activity of Rab11 is a novel mechanism for glucose hypometabolism in HD.

  14. Primary Immune Deficiency Treatment Consortium (PIDTC) report

    NARCIS (Netherlands)

    L.M. Griffith (Linda); M. Cowan (Morton); L.D. Notarangelo (Luigi Daniele); R. Kohn (Robert); J. Puck (Jennifer); S.-Y. Pai (Sung-Yun); B. Ballard (Barbara); S.C. Bauer (Sarah); J. Bleesing (Jack); M. Boyle (Marcia); R.W. Brower (Ronald); R.H. Buckley (Rebecca); M. van der Burg (Mirjam); L.M. Burroughs (Lauri); F. Candotti (Fabio); A. Cant (Andrew); T. Chatila (Talal); C. Cunningham-Rundles (Charlotte); M.C. Dinauer (Mary); J. Dvorak (Jennie); A. Filipovich (Alexandra); L.A. Fleisher (Lee); H.B. Gaspar (Bobby); T. Gungor (Tayfun); E. Haddad (Elie); E. Hovermale (Emily); F. Huang (Faith); A. Hurley (Alan); M. Hurley (Mary); S.K. Iyengar (Sudha); E.M. Kang (Elizabeth); B.R. Logan (Brent); J.R. Long-Boyle (Janel); H. Malech (Harry); S.A. McGhee (Sean); S. Modell (Sieglinde); S. Modell (Sieglinde); H.D. Ochs (Hans); R.J. O'Reilly (Richard); R. Parkman (Robertson); D. Rawlings (D.); J.M. Routes (John); P. Shearer (P.); T.N. Small (Trudy); H. Smith (H.); K.E. Sullivan (Kathleen); P. Szabolcs (Paul); A.J. Thrasher (Adrian); D. Torgerson; P. Veys (Paul); K. Weinberg (Kenneth); J.C. Zuniga-Pflucker (Juan Carlos)

    2014-01-01

    textabstractThe Primary Immune Deficiency Treatment Consortium (PIDTC) is a network of 33 centers in North America that study the treatment of rare and severe primary immunodeficiency diseases. Current protocols address the natural history of patients treated for severe combined immunodeficiency

  15. Partial resolution of bone lesions. A child with severe combined immunodeficiency disease and adenosine deaminase deficiency after enzyme-replacement therapy

    International Nuclear Information System (INIS)

    Yulish, B.S.; Stern, R.C.; Polmar, S.H.

    1980-01-01

    A child with severe combined immunodeficiency disease and adenosine deaminase deficiency, with characteristic bone dysplasia, was treated with transfusions of frozen irradiated RBCs as a means of enzyme replacement. This therapy resulted in restoration of immunologic competence and partial resolution of the bone lesions. Although the natural history of these lesions without therapy is not known, enzyme-replacement therapy may have played a role in the resolution of this patient's bone lesions

  16. Diagnosis, Treatment and Follow-Up in Four Children with Biotinidase Deficiency from Pakistan

    International Nuclear Information System (INIS)

    Afroze, B.; Wasay, M.

    2013-01-01

    Biotinidase deficiency is an inherited disorder in which the vitamin biotin is not recycled. If untreated, affected individuals develop neurological and cutaneous symptoms. Untreated individuals with biotinidase deficiency either succumb to disease or are left with significant morbidity. We describe clinical course and follow-up of 4 children from Pakistan. All 4 presented with classical symptoms of biotinidase deficiency and responded dramatically to oral biotin within days to weeks. Biotinidase deficiency is reported in Pakistani children from different part of world, however; there is no such report from Pakistan. This highlights lack of awareness of biotinidase deficiency among physicians in Pakistan. (author)

  17. prevalence of iron deficiency in children with cyanotic heart disease

    African Journals Online (AJOL)

    2009-12-01

    Dec 1, 2009 ... ... bone marrow to produce more red cells in an effort to increase the body's oxygen ... so the production of more and more red cells goes unabated leading to ... of iron deficiency was calculated as proportion of children with ...

  18. ECONOMICAL BASIS TO ADDRESS MICRONUTRIENT DEFICIENCIES IN DEVELOPING WORLD

    Directory of Open Access Journals (Sweden)

    Amirul Hassan

    2015-01-01

    Full Text Available Malnutrition has been called by economists at the World Bank as the “non-human face” of poverty,1 Adults who were malnourished as children earn at least 20% less on average than those who weren’t , 2.Malnutrition is often caused by underlying economics, i.e. the lack of money. Economics is very important in regards to malnutrition; it allows an individual to purchase nutrients. In many places around the world, a lack of money prevents the purchase of a variety of foods. The lack in variety usually leads to micronutrient malnutrition. Economics also decides the production of food in all countries around the world and the ability of a country to overcome difficult times. Thus economics affects ALL people at ALL levels of society, 3.Micronutrient deficiencies also known as ‘hidden hunger’ are determining and aggravating factors for health status and quality of life. It is estimated half of anaemia cases are due to iron deficiency , 4.  Almost half of children in low- and middle-income countries – 47% of under-fives are affected by anaemia, impairing cognitive and physical development,5. Iodine deficiency is the greatest single cause of mental retardation and brain damage. Coincidently,  the number of countries in which iodine-deficiency disorders were considered a public health concern reduced by 43% between 1993 and 2007,6.  Zinc deficiency affects children’s health and physical growth; it is also essential for mothers during pregnancy. It is estimated to cause 4% of deaths in pre-school aged children in lower-income countries. 7 . The Global Burden of Disease estimates showed that among the 26 major risk factors of the global burden of disease,8 iron deficiency ranks ninth overall, zinc deficiency is eleventh, and vitamin A deficiency, is thirteenth. Annually each developing country of the world are losing over millions or billions US $ in Gross Domestic Product (GDP to vitamins and minerals deficiencies. But scaling up core

  19. Deficient brain insulin signalling pathway in Alzheimer’s disease and diabetes

    Science.gov (United States)

    Liu, Ying; Liu, Fei; Grundke-Iqbal, Inge; Iqbal, Khalid; Gong, Cheng-Xin

    2015-01-01

    Brain glucose metabolism is impaired in Alzheimer’s disease (AD), the most common form of dementia. Type 2 diabetes mellitus (T2DM) is reported to increase the risk for dementia, including AD, but the underlying mechanism is not understood. Here, we investigated the brain insulin–PI3K–AKT signalling pathway in the autopsied frontal cortices from nine AD, 10 T2DM, eight T2DM–AD and seven control cases. We found decreases in the levels and activities of several components of the insulin–PI3K–AKT signalling pathway in AD and T2DM cases. The deficiency of insulin–PI3K–AKT signalling was more severe in individuals with both T2DM and AD (T2DM–AD). This decrease in insulin–PI3K–AKT signalling could lead to activation of glycogen synthase kinase-3β, the major tau kinase. The levels and the activation of the insulin–PI3K–AKT signalling components correlated negatively with the level of tau phosphorylation and positively with protein O-GlcNAcylation, suggesting that impaired insulin–PI3K–AKT signalling might contribute to neurodegeneration in AD through down-regulation of O-GlcNAcylation and the consequent promotion of abnormal tau hyperphosphorylation and neurodegeneration. The decrease in brain insulin–PI3K–AKT signalling also correlated with the activation of calpain I in the brain, suggesting that the decrease might be caused by calpain over-activation. Our findings provide novel insight into the molecular mechanism by which type 2 diabetes mellitus increases the risk for developing cognitive impairment and dementia in Alzheimer’s disease. PMID:21598254

  20. Newborn screening for dihydrolipoamide dehydrogenase deficiency: Citrulline as a useful analyte

    Directory of Open Access Journals (Sweden)

    Shane C. Quinonez

    2014-01-01

    Full Text Available Dihydrolipoamide dehydrogenase deficiency, also known as maple syrup urine disease (MSUD type III, is caused by the deficiency of the E3 subunit of branched chain alpha-ketoacid dehydrogenase (BCKDH, α-ketoglutarate dehydrogenase (αKGDH, and pyruvate dehydrogenase (PDH. DLD deficiency variably presents with either a severe neonatal encephalopathic phenotype or a primarily hepatic phenotype. As a variant form of MSUD, it is considered a core condition recommended for newborn screening. The detection of variant MSUD forms has proven difficult in the past with no asymptomatic DLD deficiency patients identified by current newborn screening strategies. Citrulline has recently been identified as an elevated dried blood spot (DBS metabolite in symptomatic patients affected with DLD deficiency. Here we report the retrospective DBS analysis and second-tier allo-isoleucine testing of 2 DLD deficiency patients. We show that an elevated citrulline and an elevated allo-isoleucine on second-tier testing can be used to successfully detect DLD deficiency. We additionally recommend that DLD deficiency be included in the “citrullinemia/elevated citrulline” ACMG Act Sheet and Algorithm.

  1. Deficient Circumferential Growth Is the Primary Determinant of Aortic Obstruction Attributable to Partial Elastin Deficiency.

    Science.gov (United States)

    Jiao, Yang; Li, Guangxin; Korneva, Arina; Caulk, Alexander W; Qin, Lingfeng; Bersi, Matthew R; Li, Qingle; Li, Wei; Mecham, Robert P; Humphrey, Jay D; Tellides, George

    2017-05-01

    Williams syndrome is characterized by obstructive aortopathy attributable to heterozygous loss of ELN , the gene encoding elastin. Lesions are thought to result primarily from excessive smooth muscle cell (SMC) proliferation and consequent medial expansion, although an initially smaller caliber and increased stiffness of the aorta may contribute to luminal narrowing. The relative contributions of such abnormalities to the obstructive phenotype had not been defined. We quantified determinants of luminal stenosis in thoracic aortas of Eln -/- mice incompletely rescued by human ELN . Moderate obstruction was largely because of deficient circumferential growth, most prominently of ascending segments, despite increased axial growth. Medial thickening was evident in these smaller diameter elastin-deficient aortas, with medial area similar to that of larger diameter control aortas. There was no difference in cross-sectional SMC number between mutant and wild-type genotypes at multiple stages of postnatal development. Decreased elastin content was associated with medial fibrosis and reduced aortic distensibility because of increased structural stiffness but preserved material stiffness. Elastin-deficient SMCs exhibited greater contractile-to-proliferative phenotypic modulation in vitro than in vivo. We confirmed increased medial collagen without evidence of increased medial area or SMC number in a small ascending aorta with thickened media of a Williams syndrome subject. Deficient circumferential growth is the predominant mechanism for moderate obstructive aortic disease resulting from partial elastin deficiency. Our findings suggest that diverse aortic manifestations in Williams syndrome result from graded elastin content, and SMC hyperplasia causing medial expansion requires additional elastin loss superimposed on ELN haploinsufficiency. © 2017 American Heart Association, Inc.

  2. Early Diagnosis and Hematopoietic Stem Cell Transplantation for IL10R Deficiency Leading to Very Early-Onset Inflammatory Bowel Disease Are Essential in Familial Cases

    Directory of Open Access Journals (Sweden)

    Neslihan Edeer Karaca

    2016-01-01

    Full Text Available Alterations of immune homeostasis in the gut may result in development of inflammatory bowel disease. A five-month-old girl was referred for recurrent respiratory and genitourinary tract infections, sepsis in neonatal period, chronic diarrhea, perianal abscess, rectovaginal fistula, and hyperemic skin lesions. She was born to second-degree consanguineous, healthy parents. Her elder siblings were lost at 4 months of age due to sepsis and 1 year of age due to inflammatory bowel disease, respectively. Absolute neutrophil and lymphocyte counts, immunoglobulin levels, and lymphocyte subsets were normal ruling out severe congenital neutropenia and classic severe combined immunodeficiencies. Quantitative determination of oxidative burst was normal, excluding chronic granulomatous disease. Colonoscopy revealed granulation, ulceration, and pseudopolyps, compatible with colitis. Very early-onset colitis and perianal disease leading to fistula formation suggested probability of inherited deficiencies of IL-10 or IL-10 receptor. A mutation at position c.G477A in exon of the IL10RB gene, resulting in a stop codon at position p.W159X, was identified. The patient underwent myeloablative hematopoietic stem cell transplantation from full matched father at 11 months of age. Perianal lesions, chronic diarrhea, and recurrent infections resolved after transplantation. IL-10/IL-10R deficiencies must be considered in patients with early-onset enterocolitis.

  3. Intravenous iron treatments for iron deficiency anemia in inflammatory bowel disease: a budget impact analysis of iron isomaltoside 1000 (Monofer) in the UK.

    Science.gov (United States)

    Pollock, R F; Muduma, G

    2017-12-01

    Iron deficiency is the leading cause of anemia in patients with inflammatory bowel disease (IBD). Intravenous iron is the first-line treatment for clinically active IBD or previous oral iron intolerance. The aim of the present study was to develop a comparative model of iron deficiency and delivery for iron isomaltoside (IIM), ferric carboxymaltose (FCM), low molecular weight iron dextran (LMWID), and iron sucrose (IS) in the treatment of iron deficiency anemia associated with IBD. Areas covered: A model was developed to evaluate iron delivery characteristics, resource use and costs associated with IIM, FCM, LMWID and IS. Iron deficiency was modeled using dosing tables and retreatments were modeled based on a pooled retrospective analysis. The analyses were conducted over 5 years in patients with IBD with mean bodyweight of 75.4 kg and hemoglobin levels of 10.77 g/dL based on observational data. Expert opinion: The modeling analysis showed that using IIM required 1.2 infusions (per treatment) to correct the mean iron deficit, compared with 1.6, 1.2, and 7.1 with FCM, LMWID and IS, respectively. Costs were estimated to be 2,518 pounds sterling (GBP) per patient with IIM or LMWID, relative to GBP 3,309 with FCM or GBP 14,382 with IS.

  4. Subclinical vitamin A deficiency in Israeli-Bedouin toddlers.

    Science.gov (United States)

    Coles, C L; Levy, A; Gorodischer, R; Dagan, R; Deckelbaum, R J; Blaner, W S; Fraser, D

    2004-05-01

    This study was designed to estimate the prevalence of and evaluate risk factors for subclinical vitamin A deficiency in Arab-Bedouin children at age 18 months, followed from birth. Community-based, prospective, cohort study conducted in Rahat, a large Arab-Bedouin township, located near the city of Beer Sheva in the Negev region of southern Israel. Healthy Bedouin infants (n=117) from the township, born at Soroka University Medical Center (SUMC) in Beer Sheva, were randomly recruited at birth. Enrollment was restricted to well infants born weighing >2500 g at birth. More than 15% of the children had serum retinol concentrations below 0.7 micromol/l. Male sex (odds ratio (OR) 4.17 [1.14-15.32], P=0.031), stunting at age 12 months (OR 10.09 [2.00-50.97], P=0.05) and warm season at age 18 months (OR 6.20 [1.36-28.28], P=0.018) were associated with vitamin A deficiency. Maternal education decreased the risk of vitamin A deficiency (OR 0.81 [0.68-0.95], P=0.011). Study results indicate a significant vitamin A deficiency problem among Bedouin children. Deficiency may be prevented by increasing dietary intake of vitamin A, especially during the warm season. Other interventions include preventing and controlling diarrheal diseases in order to avert nutritional stunting, and providing nutritional education to women of childbearing age. This study received financial support from the National Institute of Allergy and Infectious Diseases (AI-26497), the US-Israel Bi-national Science Foundation (BSF 90-00257), and the National Academy of Sciences/Institute of Medicine (AID/ANE 0158-G-SS-9035-00).

  5. 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 ...

  6. STAT6 deficiency ameliorates Graves' disease severity by suppressing thyroid epithelial cell hyperplasia.

    Science.gov (United States)

    Jiang, Xuechao; Zha, Bingbing; Liu, Xiaoming; Liu, Ronghua; Liu, Jun; Huang, Enyu; Qian, Tingting; Liu, Jiajing; Wang, Zhiming; Zhang, Dan; Wang, Luman; Chu, Yiwei

    2016-12-01

    Signal transducer and activator of transcription 6 (STAT6) is involved in epithelial cell growth. However, little is known regarding the STAT6 phosphorylation status in Graves' disease (GD) and its role in thyroid epithelial cells (TECs). In this study, we found that STAT6 phosphorylation (p-STAT6) was significantly increased in TECs from both GD patients and experimental autoimmune Graves' disease mice and that STAT6 deficiency ameliorated GD symptoms. Autocrine IL-4 signalling in TECs activated the phosphorylation of STAT6 via IL-4 R engagement, and the downstream targets of STAT6 were Bcl-xL and cyclin D1. Thus, the IL-4-STAT6-Bcl-xL/cyclin D1 pathway is crucial for TEC hyperplasia, which aggravates GD. More importantly, in vitro and in vivo experiments demonstrated that STAT6 phosphorylation inhibited by AS1517499 decreased TEC hyperplasia, thereby reducing serum T3 and T4 and ameliorating GD. Thus, our study reveals that in addition to the traditional pathogenesis of GD, in which autoantibody TRAb stimulates thyroid-stimulating hormone receptors and consequently produces T3, T4, TRAb could also trigger TECs producing IL-4, and IL-4 then acts in an autocrine manner to activate p-STAT6 signalling and stimulate unrestricted cell growth, thus aggravating GD. These findings suggest that STAT6 inhibitors could be potent therapeutics for treating GD.

  7. Osteomalacia as a result of vitamin D deficiency.

    Science.gov (United States)

    Bhan, Arti; Rao, Ajay D; Rao, D Sudhaker

    2010-06-01

    Osteomalacia is an end-stage bone disease of chronic and severe vitamin D or phosphate depletion of any cause. Its importance has increased because of the rising incidence of vitamin D deficiency. Yet, not all cases of osteomalacia are cured by vitamin D replacement, and furthermore, not all individuals with vitamin D deficiency develop osteomalacia. Although in the past osteomalacia was commonly caused by malabsorption, nutritional deficiency now is more common. In addition, recent literature suggests that nutritional vitamin D deficiency osteomalacia follows various bariatric surgeries for morbid obesity. Bone pain, tenderness, muscle weakness, and difficulty walking are all common clinical manifestations of osteomalacia. Diagnostic work-up involves biochemical assessment of vitamin D status and may also include a transiliac bone biopsy. Treatment is based on aggressive vitamin D repletion in most cases with follow-up biopsies if patients are started on antiresorptive or anabolic agents. Copyright 2010 Elsevier Inc. All rights reserved.

  8. Iron-Deficiency Anemia

    Medline Plus

    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 ...

  9. Emergence of a Stage-Dependent Human Liver Disease Signature with Directed Differentiation of Alpha-1 Antitrypsin-Deficient iPS Cells

    Directory of Open Access Journals (Sweden)

    Andrew A. Wilson

    2015-05-01

    Full Text Available Induced pluripotent stem cells (iPSCs provide an inexhaustible source of cells for modeling disease and testing drugs. Here we develop a bioinformatic approach to detect differences between the genomic programs of iPSCs derived from diseased versus normal human cohorts as they emerge during in vitro directed differentiation. Using iPSCs generated from a cohort carrying mutations (PiZZ in the gene responsible for alpha-1 antitrypsin (AAT deficiency, we find that the global transcriptomes of PiZZ iPSCs diverge from normal controls upon differentiation to hepatic cells. Expression of 135 genes distinguishes PiZZ iPSC-hepatic cells, providing potential clues to liver disease pathogenesis. The disease-specific cells display intracellular accumulation of mutant AAT protein, resulting in increased autophagic flux. Furthermore, we detect beneficial responses to the drug carbamazepine, which further augments autophagic flux, but adverse responses to known hepatotoxic drugs. Our findings support the utility of iPSCs as tools for drug development or prediction of toxicity.

  10. Mutations of OCTN2, an organic cation/carnitine transporter, lead to deficient cellular carnitine uptake in primary carnitine deficiency

    NARCIS (Netherlands)

    Tang, N. L.; Ganapathy, V.; Wu, X.; Hui, J.; Seth, P.; Yuen, P. M.; Wanders, R. J.; Fok, T. F.; Hjelm, N. M.

    1999-01-01

    Systemic primary carnitine deficiency (CDSP, OMIM 212140) is an autosomal recessive disease characterized by low serum and intracellular concentrations of carnitine. CDSP may present with acute metabolic derangement simulating Reye's syndrome within the first 2 years of life. After 3 years of age,

  11. X-Linked G6PD Deficiency Protects Hemizygous Males but Not Heterozygous Females against Severe Malaria

    OpenAIRE

    Guindo, Aldiouma; Fairhurst, Rick M; Doumbo, Ogobara K; Wellems, Thomas E; Diallo, Dapa A

    2007-01-01

    Editors' Summary Background. “Favism” is a condition that results from a deficiency in an enzyme called glucose-6-phosphate dehydrogenase (G6PD), and this disorder is thought to be the commonest enzyme-deficiency disease worldwide. The disease is named favism after the Italian word for broad beans (fava), which cause a classic reaction when eaten by people with G6PD deficiency. The G6PD enzyme is particularly important in red blood cells, where it protects against damage that can be caused by...

  12. X-Linked Lymphoproliferative Disease (XLP)

    Science.gov (United States)

    ... Primary Immune Deficiency Diseases (PIDDs) Primary Immune Deficiency Diseases (PIDDs) Types of PIDDs Genetics & Inheritance Talking to Your Doctor XLP primarily affects boys, and is characterized by a life-long vulnerability to Epstein-Barr virus (EBV), a common type of herpes virus ...

  13. Molecular basis of hereditary C1q deficiency-revisited: identification of several novel disease-causing mutations

    DEFF Research Database (Denmark)

    Schejbel, L; Skattum, L; Hagelberg, S

    2011-01-01

    C1q is the central pattern-recognition molecule in the classical pathway of the complement system and is known to have a key role in the crossroads between adaptive and innate immunity. Hereditary C1q deficiency is a rare genetic condition strongly associated with systemic lupus erythematosus...... and increased susceptibility to bacterial infections. However, the clinical symptoms may vary. For long, the molecular basis of C1q deficiency was ascribed to only six different mutations. In the present report, we describe five new patients with C1q deficiency, present the 12 causative mutations described till...... now and review the clinical spectrum of symptoms found in patients with C1q deficiency. With the results presented here, confirmed C1q deficiency is reported in 64 patients from at least 38 families....

  14. Prevalence of glucose-6-phosphate dehydrogenase deficiency in ...

    African Journals Online (AJOL)

    Pradeep Kumar

    2016-02-06

    Feb 6, 2016 ... Hemolytic anemia; ... G6PD deficiency is the commonest hemolytic X-linked genetic disease, which affects .... tain drugs or infection, can elicit acute hemolysis. ..... down syndrome risk: a meta-analysis from 34 studies.

  15. Management of inflammatory bowel disease-related anemia and iron deficiency with specific reference to the role of intravenous iron in current practice.

    Science.gov (United States)

    Stein, Jürgen; Aksan, Ayşegül; Farrag, Karima; Dignass, Axel; Radeke, Heinfried H

    2017-11-01

    Anemia is a common extraintestinal manifestation in patients with inflammatory bowel disease, impacting disease prognosis, morbidity, hospitalization rates and time lost from work. While iron deficiency anemia and anemia of chronic inflammation predominate, combinations of hematimetric and biochemical markers facilitate the diagnosis and targeted therapy of other etiologies according to their underlying pathophysiological causes. Intravenous iron replacement is currently recommended in IBD patients with moderate to severe anemia or intolerance to oral iron. Areas covered: This review examines the impact, pathophysiology and diagnostics of iron deficiency and anemia, compares the characteristics and safety profiles of available oral and intravenous iron preparations, and highlights issues which require consideration in decision making for therapy administration and monitoring. Expert opinion: Modern intravenous iron formulations have been shown to be safe and effective in IBD patients, allowing rapid anemia correction and repletion of iron stores. While traditional oral iron preparations are associated with increased inflammation, negative effects on the microbiome, and poor tolerance and compliance, first clinical trial data indicate that newer oral compounds such as ferric maltol and sucrosomial iron offer improved tolerability and may thus offer a viable alternative for the future.

  16. Prevention of Iron-Deficiency Anemia in Infants and Children of Preschool Age.

    Science.gov (United States)

    Fomon, Samuel J.

    Iron-deficiency anemia is almost certainly the most prevalent nutritional disorder among infants and young children in the United States. Anemia is frequently seen among children of low socioeconomic status but is probably also the most frequent nutritional deficiency disease seen among children cared for by private doctors. Possible reasons for…

  17. 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.

  18. Biotinidase deficiency presenting as recurrent myelopathy in a 7-year-old boy and a review of the literature.

    Science.gov (United States)

    Raha, Sarbani; Udani, Vrajesh

    2011-10-01

    Biotinidase deficiency may produce variable neurologic manifestations. Brainstem and spinal cord disease comprises an uncommon presentation of biotinidase deficiency. We describe a 7-year old boy with subacute progressive quadriplegia and "sighing" respirations. Severe biotinidase deficiency was established, and the patient demonstrated complete recovery with biotin supplementation. Genetic studies revealed presence of homozygous mutation in the BTD gene [c.133C>T (p.H447Y)]. Biotinidase deficiency should be considered in the differential diagnosis for subacute, long segment myelopathy, particularly with brainstem involvement. This entity is treatable; a high index of suspicion can be life-saving. We also review the literature on biotinidase deficiency presenting as spinal cord demyelinating disease. Copyright © 2011 Elsevier Inc. All rights reserved.

  19. Nutritional deficiency in citrus with symptoms of citrus variegated chlorosis disease

    Directory of Open Access Journals (Sweden)

    ME. Silva-Stenico

    Full Text Available It is well known that citrus plants that have been infected by Xylella fastidiosa display nutritional deficiencies, probably caused by production of extracellular polymers by the bacteria that block normal nutrient flow through the xylem. The aim of this work was to study the mineral composition of specific foliar areas in different stages of infection in citrus. Thus, the concentrations of macro and micronutrients in leaves of citrus infected by X. fastidiosa were measured. Samples from four infected citrus orchards in the State of São Paulo, Brazil, were respectively collected from Santa Rita do Passa Quatro, Neves Paulista, Gavião Peixoto and Paraíso counties. The presence of X. fastidiosa in leaves was confirmed by polymerase chain reaction (PCR using specific PCR primers. To understand the variation in leaf-nutrient content in citrus plants, we used foliar nutrient values from control (non-symptomatic plants as a reference. Chemometric analysis showed that the deficiency of P and K in symptomatic trees for all orchards and high concentrations of Fe, Mn and Zn were observed in chlorotic areas, although other studies revealed deficiency of zinc in leaves. This is the first report showing that a correlation between chlorotic citrus leaf and higher concentrations of Fe, Mn and Zn are observed when infected and healthy plants were compared.

  20. Biochemical signatures mimicking multiple carboxylase deficiency in children with mutations in MT-ATP6.

    Science.gov (United States)

    Larson, Austin A; Balasubramaniam, Shanti; Christodoulou, John; Burrage, Lindsay C; Marom, Ronit; Graham, Brett H; Diaz, George A; Glamuzina, Emma; Hauser, Natalie; Heese, Bryce; Horvath, Gabriella; Mattman, Andre; van Karnebeek, Clara; Lane Rutledge, S; Williamson, Amy; Estrella, Lissette; Van Hove, Johan K L; Weisfeld-Adams, James D

    2018-01-04

    Elevations of specific acylcarnitines in blood reflect carboxylase deficiencies, and have utility in newborn screening for life-threatening organic acidemias and other inherited metabolic diseases. In this report, we describe a newly-identified association of biochemical features of multiple carboxylase deficiency in individuals harboring mitochondrial DNA (mtDNA) mutations in MT-ATP6 and in whom organic acidemias and multiple carboxylase deficiencies were excluded. Using retrospective chart review, we identified eleven individuals with abnormally elevated propionylcarnitine (C3) or hydroxyisovalerylcarnitine (C5OH) with mutations in MT-ATP6, most commonly m.8993T>G in high heteroplasmy or homoplasmy. Most patients were ascertained on newborn screening; most had normal enzymatic or molecular genetic testing to exclude biotinidase and holocarboxylase synthetase deficiencies. MT-ATP6 is associated with some cases of Leigh disease; clinical outcomes in our cohort ranged from death from neurodegenerative disease in early childhood to clinically and developmentally normal after several years of follow-up. These cases expand the biochemical phenotype associated with MT-ATP6 mutations, especially m.8993T>G, to include acylcarnitine abnormalities mimicking carboxylase deficiency states. Clinicians should be aware of this association and its implications for newborn screening, and consider mtDNA sequencing in patients exhibiting similar acylcarnitine abnormalities that are biotin-unresponsive and in whom other enzymatic deficiencies have been excluded. Copyright © 2018 Elsevier B.V. and Mitochondria Research Society. All rights reserved.

  1. Predictors of Vitamin D Deficiency in Predialysis Patients with Stage ...

    African Journals Online (AJOL)

    2017-12-05

    Dec 5, 2017 ... Objective: Vitamin D status and risk factors of Vitamin D deficiency in chronic kidney disease ... common in patients with chronic kidney diseases (CKD), especially in Stage 3–5 ... METHODS ... The blood pressure and laboratory data measured within ... sphygmomanometer three times after the participant.

  2. Selenoprotein S/SEPS1 modifies endoplasmic reticulum stress in Z variant alpha1-antitrypsin deficiency.

    LENUS (Irish Health Repository)

    Kelly, Emer

    2009-06-19

    Z alpha(1)-antitrypsin (ZAAT) deficiency is a disease associated with emphysematous lung disease and also with liver disease. The liver disease of AAT deficiency is associated with endoplasmic reticulum (ER) stress. SEPS1 is a selenoprotein that, through a chaperone activity, decreases ER stress. To determine the effect of SEPS1 on ER stress in ZAAT deficiency, we measured activity of the grp78 promoter and levels of active ATF6 as markers of the unfolded protein response in HepG2 cells transfected with the mutant form of AAT, a ZAAT transgene. We evaluated levels of NFkappaB activity as a marker of the ER overload response. To determine the effect of selenium supplementation on the function of SEPS1, we investigated glutathione peroxidase activity, grp78 promoter activity, and NFkappaB activity in the presence or absence of selenium. SEPS1 reduced levels of active ATF6. Overexpression of SEPS1 also inhibited grp78 promoter and NFkappaB activity, and this effect was enhanced in the presence of selenium supplementation. This finding demonstrates a role for SEPS1 in ZAAT deficiency and suggests a possible therapeutic potential for selenium supplementation.

  3. Aldose Reductase-Deficient Mice Develop Nephrogenic Diabetes Insipidus

    Science.gov (United States)

    Ho, Horace T. B.; Chung, Sookja K.; Law, Janice W. S.; Ko, Ben C. B.; Tam, Sidney C. F.; Brooks, Heddwen L.; Knepper, Mark A.; Chung, Stephen S. M.

    2000-01-01

    Aldose reductase (ALR2) is thought to be involved in the pathogenesis of various diseases associated with diabetes mellitus, such as cataract, retinopathy, neuropathy, and nephropathy. However, its physiological functions are not well understood. We developed mice deficient in this enzyme and found that they had no apparent developmental or reproductive abnormality except that they drank and urinated significantly more than their wild-type littermates. These ALR2-deficient mice exhibited a partially defective urine-concentrating ability, having a phenotype resembling that of nephrogenic diabetes insipidus. PMID:10913167

  4. Niemann-Pick disease

    Science.gov (United States)

    NPD; Sphingomyelinase deficiency; Lipid storage disorder - Niemann-Pick disease; Lysosomal storage disease - Niemann-Pick ... lipofuscinoses or Batten disease (Wolman disease, cholesteryl ... metabolism of lipids. In: Kliegman RM, Stanton BF, St. Geme JW, ...

  5. Paroxysmal Exercise-induced Dyskinesias Caused by GLUT1 Deficiency Syndrome

    Directory of Open Access Journals (Sweden)

    Marie Mongin

    2016-03-01

    Full Text Available Background: Glucose transporter type 1 deficiency syndrome is due to de novo mutations in the SLC2A1 gene encoding the glucose transporter type 1. Phenomenology Shown: Paroxysmal motor manifestations induced by exercise or fasting may be the main manifestations of glucose transporter type 1 deficiency syndrome. Educational Value: Proper identification of the paroxysmal events and early diagnosis is important since the disease is potentially treatable.

  6. Novel mutations associated with pyruvate kinase deficiency in Brazil

    Directory of Open Access Journals (Sweden)

    Maria Carolina Costa Melo Svidnicki

    2018-01-01

    Full Text Available Background: Pyruvate kinase deficiency is a hereditary disease that affects the glycolytic pathway of the red blood cell, causing nonspherocytic hemolytic anemia. The disease is transmitted as an autosomal recessive trait and shows a marked variability in clinical expression. This study reports on the molecular characterization of ten Brazilian pyruvate kinase-deficient patients and the genotype–phenotype correlations. Method: Sanger sequencing and in silico analysis were carried out to identify and characterize the genetic mutations. A non-affected group of Brazilian individuals were also screened for the most commonly reported variants (c.1456C>T and c.1529G>A. Results: Ten different variants were identified in the PKLR gene, of which three are reported here for the first time: p.Leu61Gln, p.Ala137Val and p.Ala428Thr. All the three missense variants involve conserved amino acids, providing a rationale for the observed enzyme deficiency. The allelic frequency of c.1456C>T was 0.1% and the 1529G>A variant was not found. Conclusion: This is the first comprehensive report on molecular characterization of pyruvate kinase deficiency from South America. The results allowed us to correlate the severity of the clinical phenotype with the identified variants. Keywords: Red cell disorder, Pyruvate kinase, Mutation, Hemolytic anemia, PKLR gene

  7. Effect of vitamin D deficiency in developed countries.

    Science.gov (United States)

    Hassan-Smith, Zaki K; Hewison, Martin; Gittoes, Neil J

    2017-06-01

    Vitamin D deficiency is common worldwide with adverse effects on skeletal health. In recent years, there has been great interest in non-classical actions of vitamin D. Basic research has uncovered actions in a range of non-skeletal tissues, and observational studies have identified inverse relationships with risk of a number of disease states including sarcopenia, obesity, the metabolic syndrome, cardiovascular disease, cancer and autoimmune diseases. PubMed, Medline and Cochrane Systematic Reviews. Current evidence supports the use of vitamin D supplementation in deficiency to improve skeletal outcomes such as falls/fracture risk and bone mineral density. There is debate reflected in guidelines on optimal thresholds for circulating levels of vitamin D. Further studies are required to refine dosing regimens and treatment target levels of vitamin D. A number of studies have investigated the extra-skeletal effects of vitamin D deficiency but causality in humans has yet to be confirmed. Large-scale randomized controlled trials incorporating data on vitamin D status at baseline and follow up, adverse events, and comparison of dosing regimens are required. It is imperative that studies are carried out with a diverse range of participants (age, gender and ethnicity), and settings to allow for a more individualized approach. In addition, we would advocate incorporating cutting-edge research tools into human studies to advance our understanding of the mechanisms of vitamin D action in extra-skeletal disease. This may involve multi-metabolite analysis of vitamin D metabolites, or unbiased approaches to assess regulation of gene/protein expression in tissues of interest. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

  8. Increased glucocerebrosidase (GBA) 2 activity in GBA1 deficient mice brains and in Gaucher leucocytes.

    Science.gov (United States)

    Burke, Derek G; Rahim, Ahad A; Waddington, Simon N; Karlsson, Stefan; Enquist, Ida; Bhatia, Kailash; Mehta, Atul; Vellodi, Ashok; Heales, Simon

    2013-09-01

    Lysosomal glucocerebrosidase (GBA1) deficiency is causative for Gaucher disease. Not all individuals with GBA1 mutations develop neurological involvement raising the possibility that other factors may provide compensatory protection. One factor may be the activity of the non-lysosomal β-glucosidase (GBA2) which exhibits catalytic activity towards glucosylceramide and is reported to be highly expressed in brain tissue. Here, we assessed brain GBA2 enzymatic activity in wild type, heterozygote and GBA1 deficient mice. Additionally, we determined activity in leucocytes obtained from 13 patients with Gaucher disease, 10 patients with enzymology consistent with heterozygote status and 19 controls. For wild type animals, GBA2 accounted for over 85 % of total brain GBA activity and was significantly elevated in GBA1 deficient mice when compared to heterozygote and wild types (GBA1 deficient; 92.4 ± 5.6, heterozygote; 71.5 ± 2.4, wild type 76.8 ± 5.1 nmol/h/mg protein). For the patient samples, five Gaucher patients had GBA2 leucocyte activities markedly greater than controls. No difference in GBA2 activity was apparent between the control and carrier groups. Undetectable GBA2 activity was identified in four leucocyte preparations; one in the control group, two in the carrier group and one from the Gaucher disease group. Work is now required to ascertain whether GBA2 activity is a disease modifying factor in Gaucher disease and to identify the mechanism(s) responsible for triggering increased GBA2 activity in GBA1 deficiency states.

  9. ECONOMICAL BASIS TO ADDRESS MICRONUTRIENT DEFICIENCIES IN DEVELOPING WORLD

    Directory of Open Access Journals (Sweden)

    Amirul Hassan

    2015-12-01

    Full Text Available Malnutrition has been called by economists at the World Bank as the “non-human face” of poverty,1 Adults who were malnourished as children earn at least 20% less on average than those who weren’t , 2.Malnutrition is often caused by underlying economics, i.e. the lack of money. Economics is very important in regards to malnutrition; it allows an individual to purchase nutrients. In many places around the world, a lack of money prevents the purchase of a variety of foods. The lack in variety usually leads to micronutrient malnutrition. Economics also decides the production of food in all countries around the world and the ability of a country to overcome difficult times. Thus economics affects ALL people at ALL levels of society, 3.Micronutrient deficiencies also known as ‘hidden hunger’ are determining and aggravating factors for health status and quality of life. It is estimated half of anaemia cases are due to iron deficiency , 4.  Almost half of children in low- and middle-income countries – 47% of under-fives are affected by anaemia, impairing cognitive and physical development,5. Iodine deficiency is the greatest single cause of mental retardation and brain damage. Coincidently,  the number of countries in which iodine-deficiency disorders were considered a public health concern reduced by 43% between 1993 and 2007,6.  Zinc deficiency affects children’s health and physical growth; it is also essential for mothers during pregnancy. It is estimated to cause 4% of deaths in pre-school aged children in lower-income countries. 7 . The Global Burden of Disease estimates showed that among the 26 major risk factors of the global burden of disease,8 iron deficiency ranks ninth overall, zinc deficiency is eleventh, and vitamin A deficiency, is thirteenth. Annually each developing country of the world are losing over millions or billions US $ in Gross Domestic Product (GDP to vitamins and minerals deficiencies. But scaling up

  10. Evaluation of vitamin B 12 deficiency in various clinical condition

    International Nuclear Information System (INIS)

    Baig, J.A.; Alam, J.M.; Kazmi, T.; Waseem, S.; Hussain, A.; Arif, S.; Shaheen, R.; Sultana, I.

    2010-01-01

    Low levels of vitamin B 12 have been associated with several clinical conditions. However no single symptom or group of symptoms can be made responsible. Reported causes of deficiency among older population are hematologic or neurological, followed by gastrointestinal and possibly vascular symptoms. The present prospective observational study was, hence, initiated to evaluate the underlying clinical condition or symptoms associated with vitamin B12 deficiency. The study was prospective observational and carried out on 121 patients (males, n=63 and females, n=58) for the period from January 1, 2004 to January 24, 2007. Age ranges were between 16 - 70 years, and categorized as > 60 yrs and < 60 years. All blood parameters were analyzed by standardized methods on automated analyzers. The deficiency was found to be more prevalent in males and increased from 52.06% to 58.10% in individuals with vitamin B12 <150 pg/ml. Mal nourishment was noted among the most subjects and weakness and anemia were frequent clinical findings (35.55%, n=43, 14%, n=51). Other clinical conditions were neuropsychiatric. Whereas less frequent findings were paraesthesia and gastrointestinal symptoms. Hypertension was more prevalent in vitamin B12 deficient individuals followed by diabetes, dementia, stroke, ischemic heart disease and Parkinson's disease. (author)

  11. Resurrection of vitamin D deficiency and rickets

    Science.gov (United States)

    Holick, Michael F.

    2006-01-01

    The epidemic scourge of rickets in the 19th century was caused by vitamin D deficiency due to inadequate sun exposure and resulted in growth retardation, muscle weakness, skeletal deformities, hypocalcemia, tetany, and seizures. The encouragement of sensible sun exposure and the fortification of milk with vitamin D resulted in almost complete eradication of the disease. Vitamin D (where D represents D2 or D3) is biologically inert and metabolized in the liver to 25-hydroxyvitamin D [25(OH)D], the major circulating form of vitamin D that is used to determine vitamin D status. 25(OH)D is activated in the kidneys to 1,25-dihydroxyvitamin D [1,25(OH)2D], which regulates calcium, phosphorus, and bone metabolism. Vitamin D deficiency has again become an epidemic in children, and rickets has become a global health issue. In addition to vitamin D deficiency, calcium deficiency and acquired and inherited disorders of vitamin D, calcium, and phosphorus metabolism cause rickets. This review summarizes the role of vitamin D in the prevention of rickets and its importance in the overall health and welfare of infants and children. PMID:16886050

  12. Testosterone deficiency syndrome: cellular and molecular mechanism of action.

    Science.gov (United States)

    Carruthers, Malcolm

    2013-02-01

    There is virtually no correlation between what are generally accepted to be the symptoms of deficient androgen in men and levels of androgens as measured in the laboratory. Now that androgen deficiency is being shown to play a part in conditions as diverse as metabolic syndrome, diabetes, and coronary heart disease, a hypothesis is needed to explain this apparent discrepancy between measured androgen levels and our understanding of the symptoms of androgen deficiency. When the possible mechanisms for androgen actions are considered, one explanation emerges that androgen may act much like insulin in persons with type 2 diabetes mellitus: the degree of androgen resistance may be variable depending on the organs or systems considered. Therefore, the symptoms can result from altered or damaged synthesis of androgen synthesis or regulation, elevated androgen binding, a reduction in tissue response, or decreased as a result of polymorphism and aging. Genomic transcription and translation may also be affected. As with diabetes, in adult male androgen deficiency, it is suggested that the definition of androgen deficiency should be based on individual physiology, with the requirements of the individual at a particular stage of life setting the baseline against which any deficiency of androgens or androgen metabolites, either absolute or relative, is determined. This approach will affect the terminology, etiology, diagnosis, and treatment of androgen deficiency.

  13. Behavioral phenotyping of Parkin-deficient mice: looking for early preclinical features of Parkinson's disease.

    Directory of Open Access Journals (Sweden)

    Daniel Rial

    Full Text Available There is considerable evidence showing that the neurodegenerative processes that lead to sporadic Parkinson's disease (PD begin many years before the appearance of the characteristic motor symptoms. Neuropsychiatric, sensorial and cognitive deficits are recognized as early non-motor manifestations of PD, and are not attenuated by the current anti-parkinsonian therapy. Although loss-of-function mutations in the parkin gene cause early-onset familial PD, Parkin-deficient mice do not display spontaneous degeneration of the nigrostriatal pathway or enhanced vulnerability to dopaminergic neurotoxins such as 6-OHDA and MPTP. Here, we employed adult homozygous C57BL/6 mice with parkin gene deletion on exon 3 (parkin-/- to further investigate the relevance of Parkin in the regulation of non-motor features, namely olfactory, emotional, cognitive and hippocampal synaptic plasticity. Parkin-/- mice displayed normal performance on behavioral tests evaluating olfaction (olfactory discrimination, anxiety (elevated plus-maze, depressive-like behavior (forced swimming and tail suspension and motor function (rotarod, grasping strength and pole. However, parkin-/- mice displayed a poor performance in the open field habituation, object location and modified Y-maze tasks suggestive of procedural and short-term spatial memory deficits. These behavioral impairments were accompanied by impaired hippocampal long-term potentiation (LTP. These findings indicate that the genetic deletion of parkin causes deficiencies in hippocampal synaptic plasticity, resulting in memory deficits with no major olfactory, emotional or motor impairments. Therefore, parkin-/- mice may represent a promising animal model to study the early stages of PD and for testing new therapeutic strategies to restore learning and memory and synaptic plasticity impairments in PD.

  14. Seven Patients With Transcobalamin Deficiency Diagnosed Between 2010 and 2014

    DEFF Research Database (Denmark)

    Yildirim, Zuhal K; Nexo, Ebba; Rupar, Tony

    2017-01-01

    Transcobalamin deficiency (OMIM 275350) is a rare autosomal recessive disease presenting with nonspecific clinical features in early infancy. We report the clinical and laboratory manifestations of 7 children diagnosed with transcobalamin deficiency. All patients were admitted between 2 and 4 mon....... In conclusion, 1 mg of intramuscular CN-Cbl every week suffices for hematological improvement but not for normal neurological development in patients who all had relapse due to decrease or cessation of treatment....

  15. Alpha-1-antitrypsin deficiency in Madeira (Portugal): the highest prevalence in the world.

    Science.gov (United States)

    Spínola, Carla; Bruges-Armas, Jácome; Pereira, Conceição; Brehm, António; Spínola, Hélder

    2009-10-01

    Alpha-1-antitrypsin (AAT) deficiency is a common genetic disease which affects both lung and liver. Early diagnosis can help asymptomatic patients to adjust their lifestyle choices in order to reduce the risk of Chronic Obstructive Pulmonary Disease (COPD). The determination of this genetic deficiency prevalence in Madeira Island (Portugal) population is important to clarify susceptibility and define the relevance of performing genetic tests for AAT on individuals at risk for COPD. Two hundred samples of unrelated individuals from Madeira Island were genotyped for the two most common AAT deficiency alleles, PI*S and PI*Z, using Polymerase Chain Reaction-Mediated Site-Directed Mutagenesis. Our results show one of the highest frequencies for both mutations when compared to any already studied population in the world. In fact, PI*S mutation has the highest prevalence (18%), and PI*Z mutation (2.5%) was the third highest worldwide. The frequency of AAT deficiency genotypes in Madeira (PI*ZZ, PI*SS, and PI*SZ) is estimated to be the highest in the world: 41 per 1000. This high prevalence of AAT deficiency on Madeira Island reveals an increased genetic susceptibility to COPD and suggests a routine genetic testing for individuals at risk.

  16. Prevalence and factors promoting the occurrence of vitamin D deficiency in the elderly.

    Science.gov (United States)

    Wyskida, Magdalena; Wieczorowska-Tobis, Katarzyna; Chudek, Jerzy

    2017-03-13

    Vitamin D deficiency affects a large part of the population of elderly people, especially women, who live in moderate climate countries due to a reduced amount of vitamin D in the diet (small sea fish consumption) and reduced content of 7-dehydrocholesterol, which causes decreased skin synthesis. The lowest seasonal concentration of 25(OH)D3 is usually observed during winter and spring. Sun exposure influences 25(OH)D3 concentration more strongly in men than in women. Sociodemographic factors that increase the risk of vitamin D deficiency in the elderly include poor environmental conditions, low economic status, lower educational level, drug exposure (smoking), reduced physical activity, overall poor health and obesity, which causes reduced skin exposure to sunlight. The use of medications or supplements that contain vitamin D and staying in a nursing home that employ such supplementation are factors that prevent deficiency. Significant prevalence of diseases of the gastrointestinal tract may contribute to cholecalciferol and ergocalciferol malabsorption or impair their liver transformation. In addition, the high incidence of chronic kidney disease in old age reduces processing hydroxylation of vitamin D and the formation of active metabolites. Vitamin D deficiency can not only cause bone mineralization disorders, but also increase incidence of cardiovascular diseases, cancers, type 2 diabetes and depression. The aim of this study was to summarize current knowledge about the risk factors of vitamin D deficiency development in the elderly population.

  17. The role of vitamin D deficiency in cardiovascular disease: where do we stand in 2013?

    NARCIS (Netherlands)

    Pilz, S.; Gaksch, M.; O'Hartaigh, B.; Tomaschitz, A.; Marz, W.

    2013-01-01

    The high worldwide prevalence of vitamin D deficiency is largely the result of low sunlight exposure with subsequently limited cutaneous vitamin D production. Classic manifestations of vitamin D deficiency are linked to disturbances in bone and mineral metabolism, but the identification of the

  18. Iron-Deficiency Anemia

    Medline Plus

    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- ...

  19. Laryngeal Muscles Are Spared in the Dystrophin Deficient "mdx" Mouse

    Science.gov (United States)

    Thomas, Lisa B.; Joseph, Gayle L.; Adkins, Tracey D.; Andrade, Francisco H.; Stemple, Joseph C.

    2008-01-01

    Purpose: "Duchenne muscular dystrophy (DMD)" is caused by the loss of the cytoskeletal protein, dystrophin. The disease leads to severe and progressive skeletal muscle wasting. Interestingly, the disease spares some muscles. The purpose of the study was to determine the effects of dystrophin deficiency on 2 intrinsic laryngeal muscles, the…

  20. [Different patterns of 123I-BMIPP myocardial accumulation in patients with type I and II CD36 deficiency].

    Science.gov (United States)

    Watanabe, K; Toba, K; Ogawa, Y; Aizawa, Y; Tanabe, N; Miyajima, S; Kusano, Y; Nagatomo, T; Hirokawa, Y

    1997-12-01

    The CD36 molecule is a multifunctional membrane type receptor glycoprotein that reacts with thrombospondin, collagen, oxidized LDL and long-chain fatty acids (LCFA). LCFA are one of the major cardiac energy substrates, hence LCFA metabolism may have an important role in cardiac diseases. In this study, we analyzed CD36 expression in 200 patients with heart diseases [44 patients with hypertrophic cardiomyopathy (HCM), 16 with dilated cardiomyopathy (DCM), 26 with old myocardial infarction (OMI), 55 with angina pectoris (AP) and 59 with other miscellaneous heart diseases] using a flow cytometer. 123I-beta-methyl-p-iodophenylpentadecanoic acid (BMIPP) myocardial accumulation was also examined in some patients. Eight patients (2 with HCM, 1 with DCM, 2 with OMI, and 3 with AP) were diagnosed as having type I CD36 deficiency (neither platelets nor monocytes expressed CD36). Sixteen patients (3 with HCM, 1 with DCM, 1 with OMI, 8 with AP, and 3 with other heart diseases) showed type II CD36 deficiency (monocytes expressed CD36 but platelets did not). In all 8 patients with type I CD36 deficiency, there was no BMIPP accumulation in the heart. However, in 13 patients with type II CD36 deficiency, focally reduced BMIPP accumulation was observed, but there were no patients without BMIPP accumulation. CD36 deficiency was observed in a higher proportion (12%) of patients with heart disease in this study than in a reported control study. Type I CD36 deficiency is associated with absence of BMIPP accumulation in the heart, hence it may have an important role in LCFA metabolic disorders and some types of cardiac hypertrophy as well as other heart diseases.

  1. Different patterns of 123I-BMIPP myocardial accumulation in patients with type I and II CD36 deficiency

    International Nuclear Information System (INIS)

    Watanabe, Kenichi; Nagatomo, Takafumi; Toba, Ken; Ogawa, Yusuke; Aizawa, Yoshifusa; Tanabe, Naohito; Miyajima, Seiichi; Kusano, Yoriko; Hirokawa, Yoichi.

    1997-01-01

    The CD36 molecule is a multifunctional membrane type receptor glycoprotein that reacts with thrombospondin, collagen, oxidized LDL and long-chain fatty acids (LCFA). LCFA are one of the major cardiac energy substrates, hence LCFA metabolism may have an important role in cardiac diseases. In this study, we analyzed CD36 expression in 200 patients with heart diseases (44 patients with hypertrophic cardiomyopathy (HCM), 16 with dilated cardiomyopathy (DCM), 26 with old myocardial infarction (OMI), 55 with angina pectoris (AP) and 59 with other miscellaneous heart diseases) using a flow cytometer. 123 I-β-methyl-p-iodophenylpentadecanoic acid (BMIPP) myocardial accumulation was also examined in some patients. Eight patients (2 with HCM, 1 with DCM, 2 with OMI, and 3 with AP) were diagnosed as having type I CD36 deficiency (neither platelets nor monocytes expressed CD36). Sixteen patients (3 with HCM, 1 with DCM, 1 with OMI, 8 with AP, and 3 with other heart diseases) showed type II CD36 deficiency (monocytes expressed CD36 but platelets did not). In all 8 patients with type I CD36 deficiency, there was no BMIPP accumulation in the heart. However, in 13 patients with type II CD36 deficiency, focally reduced BMIPP accumulation was observed, but there were no patients without BMIPP accumulation. CD36 deficiency was observed in a higher proportion (12%) of patients with heart disease in this study than in a reported control study. Type I CD36 deficiency is associated with absence of BMIPP accumulation in the heart, hence it may have an important role in LCFA metabolic disorders and some types of cardiac hypertrophy as well as other heart diseases. (author)

  2. Small RNA profiling reveals phosphorus deficiency as a contributing factor in symptom expression for citrus huanglongbing disease.

    Science.gov (United States)

    Zhao, Hongwei; Sun, Ruobai; Albrecht, Ute; Padmanabhan, Chellappan; Wang, Airong; Coffey, Michael D; Girke, Thomas; Wang, Zonghua; Close, Timothy J; Roose, Mikeal; Yokomi, Raymond K; Folimonova, Svetlana; Vidalakis, Georgios; Rouse, Robert; Bowman, Kim D; Jin, Hailing

    2013-03-01

    Huanglongbing (HLB) is a devastating citrus disease that is associated with bacteria of the genus 'Candidatus Liberibacter' (Ca. L.). Powerful diagnostic tools and management strategies are desired to control HLB. Host small RNAs (sRNA) play a vital role in regulating host responses to pathogen infection and are used as early diagnostic markers for many human diseases, including cancers. To determine whether citrus sRNAs regulate host responses to HLB, sRNAs were profiled from Citrus sinensis 10 and 14 weeks post grafting with Ca. L. asiaticus (Las)-positive or healthy tissue. Ten new microRNAs (miRNAs), 76 conserved miRNAs, and many small interfering RNAs (siRNAs) were discovered. Several miRNAs and siRNAs were highly induced by Las infection, and can be potentially developed into early diagnosis markers of HLB. miR399, which is induced by phosphorus starvation in other plant species, was induced specifically by infection of Las but not Spiroplasma citri that causes citrus stubborn-a disease with symptoms similar to HLB. We found a 35% reduction of phosphorus in Las-positive citrus trees compared to healthy trees. Applying phosphorus oxyanion solutions to HLB-positive sweet orange trees reduced HLB symptom severity and significantly improved fruit production during a 3-year field trial in south-west Florida. Our molecular, physiological, and field data suggest that phosphorus deficiency is linked to HLB disease symptomology.

  3. A link between premenopausal iron deficiency and breast cancer malignancy

    International Nuclear Information System (INIS)

    Jian, Jinlong; Li, Jinqing; Huang, Xi; Yang, Qing; Shao, Yongzhao; Axelrod, Deborah; Smith, Julia; Singh, Baljit; Krauter, Stephanie; Chiriboga, Luis; Yang, Zhaoxu

    2013-01-01

    Young breast cancer (BC) patients less than 45 years old are at higher risk of dying from the disease when compared to their older counterparts. However, specific risk factors leading to this poorer outcome have not been identified. One candidate is iron deficiency, as this is common in young women and a clinical feature of young age. In the present study, we used immuno-competent and immuno-deficient mouse xenograft models as well as hemoglobin as a marker of iron status in young BC patients to demonstrate whether host iron deficiency plays a pro-metastatic role. We showed that mice fed an iron-deficient diet had significantly higher tumor volumes and lung metastasis compared to those fed normal iron diets. Iron deficiency mainly altered Notch but not TGF-β and Wnt signaling in the primary tumor, leading to the activation of epithelial mesenchymal transition (EMT). This was revealed by increased expression of Snai1 and decreased expression of E-cadherin. Importantly, correcting iron deficiency by iron therapy reduced primary tumor volume, lung metastasis, and reversed EMT markers in mice. Furthermore, we found that mild iron deficiency was significantly associated with lymph node invasion in young BC patients (p<0.002). Together, our finding indicates that host iron deficiency could be a contributor of poor prognosis in young BC patients

  4. The evolution of radiation-induced growth hormone deficiency in adults is determined by the baseline growth hormone status

    Energy Technology Data Exchange (ETDEWEB)

    Toogood, A.A.; Ryder, W.D.J.; Beardwell, C.G.; Shalet, S.M. [Christie Hospital and Holt Radium Inst., Manchester (United Kingdom)

    1995-07-01

    Recent studies of GH replacement have suggested several beneficial effects for GH deficient adults. It would therefore be helpful to predict the time of onset of GH deficiency after external pituitary irradiation. We have studied the evolution of GH deficiency with time in patients irradiated for pituitary adenomas and other hypothalamic pituitary tumours. The results provide an insight into the pattern of the decline in GH secretion following radiotherapy in patients with pituitary disease and the factors affecting it. This information will help the clinician predict the frequency and timing of GH deficiency in patients irradiated for pituitary disease and the potential need for GH replacement therapy. (Author).

  5. Five novel glucose-6-phosphate dehydrogenase deficiency haplotypes correlating with disease severity

    Directory of Open Access Journals (Sweden)

    Dallol Ashraf

    2012-09-01

    Full Text Available Abstract Background Glucose-6-phosphate dehydrogenase (G6PD, EC 1.1.1.49 deficiency is caused by one or more mutations in the G6PD gene on chromosome X. An association between enzyme levels and gene haplotypes remains to be established. Methods In this study, we determined G6PD enzyme levels and sequenced the coding region, including the intron-exon boundaries, in a group of individuals (163 males and 86 females who were referred to the clinic with suspected G6PD deficiency. The sequence data were analysed by physical linkage analysis and PHASE haplotype reconstruction. Results All previously reported G6PD missense changes, including the AURES, MEDITERRANEAN, A-, SIBARI, VIANGCHAN and ANANT, were identified in our cohort. The AURES mutation (p.Ile48Thr was the most common variant in the cohort (30% in males patients followed by the Mediterranean variant (p.Ser188Phe detectable in 17.79% in male patients. Variant forms of the A- mutation (p.Val68Met, p.Asn126Asp or a combination of both were detectable in 15.33% of the male patients. However, unique to this study, several of such mutations co-existed in the same patient as shown by physical linkage in males or PHASE haplotype reconstruction in females. Based on 6 non-synonymous variants of G6PD, 13 different haplotypes (13 in males, 8 in females were identified. Five of these were previously unreported (Jeddah A, B, C, D and E and were defined by previously unreported combinations of extant mutations where patients harbouring these haplotypes exhibited severe G6PD deficiency. Conclusions Our findings will help design a focused population screening approach and provide better management for G6PD deficiency patients.

  6. Isotope techniques in studies of selenium deficiency and toxicity syndromes in farm animals

    International Nuclear Information System (INIS)

    Giese, W.W.

    1984-01-01

    In a brief review of the Se deficiency syndrome in ruminants, studies using non-isotopic methods are applied to an introductory description of the disease. They include methods currently applied for determining Se deficiency status in feed and in ruminant animals. Detection of potential white muscle disease in lambs and calves is discussed. The application of 75 Se in studies on absorption, tissue distribution and excretion under feeding regimes with different Se levels and partly with addition of SO 4 ions or vitamin E is reviewed. In vitro studies with 75 Se include a description of the 75 Se uptake test with red blood cells, the metabolism of selenite, selenate and selenomethionine in rumen microorganisms, and the distribution of 75 Se in cow's and goat's milk. Methods of Se supplementation in Se-deficient areas are summarized and tests with 75 Se-labelled ruminal pellets in sheep and cattle are described. The Se toxicity syndrome is surveyed with respect to causative agents, symptomatology and gross pathology. Special reference is made to the blind staggers and the alkali disease types of selenosis. Isotope techniques are found to be less frequently applied in studies on Se toxicity than in Se deficiency studies. (author)

  7. Prevalence of Growth Hormone Deficiency in Hashimoto's Thyroiditis

    NARCIS (Netherlands)

    Eskes, Silvia A.; Endert, Erik; Fliers, Eric; Wiersinga, Wilmar M.

    2010-01-01

    Context: Autoimmune hypophysitis can result in GH deficiency (GHD) and is associated with other autoimmune endocrine diseases like Hashimoto's thyroiditis. Recent studies suggest a high prevalence (5%) of GHD in Hashimoto's thyroiditis. Objective: Our objective was to establish the prevalence of GHD

  8. TLR4 deficiency promotes autophagy during cigarette smoke-induced pulmonary emphysema.

    Science.gov (United States)

    An, Chang Hyeok; Wang, Xiao Mei; Lam, Hilaire C; Ifedigbo, Emeka; Washko, George R; Ryter, Stefan W; Choi, Augustine M K

    2012-11-01

    Toll-like receptors (TLRs) exert important nonimmune functions in lung homeostasis. TLR4 deficiency promotes pulmonary emphysema. We examined the role of TLR4 in regulating cigarette smoke (CS)-induced autophagy, apoptosis, and emphysema. Lung tissue was obtained from chronic obstructive lung disease (COPD) patients. C3H/HeJ (Tlr4-mutated) mice and C57BL/10ScNJ (Tlr4-deficient) mice and their respective control strains were exposed to chronic CS or air. Human or mouse epithelial cells (wild-type, Tlr4-knockdown, and Tlr4-deficient) were exposed to CS-extract (CSE). Samples were analyzed for TLR4 expression, and for autophagic or apoptotic proteins by Western blot analysis or confocal imaging. Chronic obstructive lung disease lung tissues and human pulmonary epithelial cells exposed to CSE displayed increased TLR4 expression, and increased autophagic [microtubule-associated protein-1 light-chain-3B (LC3B)] and apoptotic (cleaved caspase-3) markers. Beas-2B cells transfected with TLR4 siRNA displayed increased expression of LC3B relative to control cells, basally and after exposure to CSE. The basal and CSE-inducible expression of LC3B and cleaved caspase-3 were elevated in pulmonary alveolar type II cells from Tlr4-deficient mice. Wild-type mice subjected to chronic CS-exposure displayed airspace enlargement;, however, the Tlr4-mutated or Tlr4-deficient mice exhibited a marked increase in airspace relative to wild-type mice after CS-exposure. The Tlr4-mutated or Tlr4-deficient mice showed higher levels of LC3B under basal conditions and after CS exposure. The expression of cleaved caspase-3 was markedly increased in Tlr4-deficient mice exposed to CS. We describe a protective regulatory function of TLR4 against emphysematous changes of the lung in response to CS.

  9. [Deficiency of triosephosphate isomerase. Apropos of 2 new cases].

    Science.gov (United States)

    Delso Martínez, M C; Uriel Miñana, P; Pérez Lugmus, G; Giménez Mas, J A; Baldellou Vázquez, A

    1983-08-01

    Two siblings, born of a no consanguineous couple, a female and a male, affected by a severe and progressive neurological disease and chronic hemolytic anemia are presented. Their clinical, hematological, biochemical and pathological studies are discussed. One of the patients showed a triosephosphate isomerase deficiency and the carrier condition of their parents was tested. Commentaries about physiopathology of this disease are made.

  10. Impact of CD1d deficiency on metabolism.

    Directory of Open Access Journals (Sweden)

    Maya E Kotas

    Full Text Available Invariant natural killer T cells (iNKTs are innate-like T cells that are highly concentrated in the liver and recognize lipids presented on the MHC-like molecule CD1d. Although capable of a myriad of responses, few essential functions have been described for iNKTs. Among the many cell types of the immune system implicated in metabolic control and disease, iNKTs seem ideally poised for such a role, yet little has been done to elucidate such a possible function. We hypothesized that lipid presentation by CD1d could report on metabolic status and engage iNKTs to regulate cellular lipid content through their various effector mechanisms. To test this hypothesis, we examined CD1d deficient mice in a variety of metabolically stressed paradigms including high fat feeding, choline-deficient feeding, fasting, and acute inflammation. CD1d deficiency led to a mild exacerbation of steatosis during high fat or choline-deficient feeding, accompanied by impaired hepatic glucose tolerance. Surprisingly, however, this phenotype was not observed in Jα18⁻/⁻ mice, which are deficient in iNKTs but express CD1d. Thus, CD1d appears to modulate some metabolic functions through an iNKT-independent mechanism.

  11. Recurrence of Crystalline Nephropathy after Kidney Transplantation in APRT Deficiency and Primary Hyperoxaluria

    Directory of Open Access Journals (Sweden)

    Guillaume Bollée

    2015-09-01

    Full Text Available Purpose of review: To provide transplant physicians with a summary of the pathogenesis and diagnosis of adenine phosphoribosyl transferase (APRT deficiency and primary hyperoxaluria and, focussed on kidney transplantation, and to discuss interventions aimed at preventing and treating the recurrence of crystalline nephropathy in renal transplant recipients. Source of information: Pubmed literature search. Setting: Primary hyperoxaluria and APRT deficiency are rare inborn errors of human metabolism. The hallmark of these diseases is the overproduction and urinary excretion of compounds (2,8 dihydroxyadenine in APRT deficiency, oxalate in primary hyperoxaluria that form urinary crystals. Although recurrent urolithiasis represents the main clinical feature of these diseases, kidney injury can occur as a result of crystal precipitation within the tubules and interstitium, a condition referred to as crystalline nephropathy. Some patients develop end-stage renal disease (ESRD and may become candidates for kidney transplantation. Since kidney transplantation does not correct the underlying metabolic defect, transplant recipients have a high risk of recurrence of crystalline nephropathy, which can lead to graft loss. In some instances, the disease remains undiagnosed until after the occurrence of ESRD or even after kidney transplantation. Key messages: Patients with APRT deficiency or primary hyperoxaluria may develop ESRD as a result of crystalline nephropathy. In the absence of diagnosis and adequate management, the disease is likely to recur after kidney transplantation, which often leads to rapid loss of renal allograft function. Primary hyperoxaluria, but not APRT deficiency, becomes a systemic disease at low GFR with oxalate deposition leading to malfunction in non-renal organs (systemic oxalosis. We suggest that these diagnoses should be considered in patients with low glomerular filtration rate (GFR and a history of kidney stones. In APRT

  12. In a model of Batten disease, palmitoyl protein thioesterase-1 deficiency is associated with brown adipose tissue and thermoregulation abnormalities.

    Directory of Open Access Journals (Sweden)

    Alfia Khaibullina

    Full Text Available Infantile neuronal ceroid lipofuscinosis (INCL is a fatal neurodegenerative disorder caused by a deficiency of palmitoyl-protein thioesterase-1 (PPT1. We have previously shown that children with INCL have increased risk of hypothermia during anesthesia and that PPT1-deficiency in mice is associated with disruption of adaptive energy metabolism, downregulation of peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α, and mitochondrial dysfunction. Here we hypothesized that Ppt1-knockout mice, a well-studied model of INCL that shows many of the neurologic manifestations of the disease, would recapitulate the thermoregulation impairment observed in children with INCL. We also hypothesized that when exposed to cold, Ppt1-knockout mice would be unable to maintain body temperature as in mice thermogenesis requires upregulation of Pgc-1α and uncoupling protein 1 (Ucp-1 in brown adipose tissue. We found that the Ppt1-KO mice had lower basal body temperature as they aged and developed hypothermia during cold exposure. Surprisingly, this inability to maintain body temperature during cold exposure in Ppt1-KO mice was associated with an adequate upregulation of Pgc-1α and Ucp-1 but with lower levels of sympathetic neurotransmitters in brown adipose tissue. In addition, during baseline conditions, brown adipose tissue of Ppt1-KO mice had less vacuolization (lipid droplets compared to wild-type animals. After cold stress, wild-type animals had significant decreases whereas Ppt1-KO had insignificant changes in lipid droplets compared with baseline measurements, thus suggesting that Ppt1-KO had less lipolysis in response to cold stress. These results uncover a previously unknown phenotype associated with PPT1 deficiency, that of altered thermoregulation, which is associated with impaired lipolysis and neurotransmitter release to brown adipose tissue during cold exposure. These findings suggest that INCL should be added to the list of

  13. Chemokine-like receptor 1 deficiency does not affect the development of insulin resistance and nonalcoholic fatty liver disease in mice.

    Directory of Open Access Journals (Sweden)

    Nanda Gruben

    Full Text Available The adipokine chemerin and its receptor, chemokine-like receptor 1 (Cmklr1, are associated with insulin resistance and nonalcoholic fatty liver disease (NAFLD, which covers a broad spectrum of liver diseases, ranging from simple steatosis to nonalcoholic steatohepatitis (NASH. It is possible that chemerin and/or Cmklr1 exert their effects on these disorders through inflammation, but so far the data have been controversial. To gain further insight into this matter, we studied the effect of whole-body Cmklr1 deficiency on insulin resistance and NAFLD. In view of the primary role of macrophages in hepatic inflammation, we also transplanted bone marrow from Cmklr1 knock-out (Cmklr1-/- mice and wild type (WT mice into low-density lipoprotein receptor knock-out (Ldlr-/- mice, a mouse model for NASH. All mice were fed a high fat, high cholesterol diet containing 21% fat from milk butter and 0.2% cholesterol for 12 weeks. Insulin resistance was assessed by an oral glucose tolerance test, an insulin tolerance test, and by measurement of plasma glucose and insulin levels. Liver pathology was determined by measuring hepatic inflammation, fibrosis, lipid accumulation and the NAFLD activity score (NAS. Whole-body Cmklr1 deficiency did not affect body weight gain or food intake. In addition, we observed no differences between WT and Cmklr1-/- mice for hepatic inflammatory and fibrotic gene expression, immune cell infiltration, lipid accumulation or NAS. In line with this, we detected no differences in insulin resistance. In concordance with whole-body Cmklr1 deficiency, the absence of Cmklr1 in bone marrow-derived cells in Ldlr-/- mice did not affect their insulin resistance or liver pathology. Our results indicate that Cmklr1 is not involved in the pathogenesis of insulin resistance or NAFLD. Thus, we recommend that the associations reported between Cmklr1 and insulin resistance or NAFLD should be interpreted with caution.

  14. Vitamin D deficiency is associated with impaired disease control in asthma-COPD overlap syndrome patients.

    Science.gov (United States)

    Odler, Balázs; Ivancsó, István; Somogyi, Vivien; Benke, Kálmán; Tamási, Lilla; Gálffy, Gabriella; Szalay, Balázs; Müller, Veronika

    2015-01-01

    The association between vitamin D and clinical parameters in obstructive lung diseases (OLDs), including COPD and bronchial asthma, was previously investigated. As asthma-COPD overlap syndrome (ACOS) is a new clinical entity, the prevalence of vitamin D levels in ACOS is unknown. Our aim was to assess the levels of circulating vitamin D (25-hydroxyvitamin D [25(OH)D]) in different OLDs, including ACOS patients, and its correlation with clinical parameters. A total of 106 men and women (control, n=21; asthma, n=44; COPD, n=21; and ACOS, n=20) were involved in the study. All patients underwent detailed clinical examinations; disease control and severity was assessed by disease-specific questionnaires (COPD assessment test, asthma control test, and modified Medical Research Council); furthermore, 25(OH)D levels were measured in all patients. The 25(OH)D level was significantly lower in ACOS and COPD groups compared to asthma group (16.86±1.79 ng/mL and 14.27±1.88 ng/mL vs 25.66±1.91 ng/mL). A positive correlation was found between 25(OH)D level and forced expiratory volume in 1 second (r=0.4433; PD level showed a positive correlation in the ACOS (r=0.4761; P=0.0339) but not in the asthma group. Higher COPD assessment test total scores correlated with decreased 25(OH)D in ACOS (r=-0.4446; P=0.0495); however, this was not observed in the COPD group. Vitamin D deficiency is present in ACOS patients and circulating 25(OH)D level may affect disease control and severity.

  15. Managing vitamin D deficiency in children

    OpenAIRE

    Michie, Colin; Bangalore, Sathish

    2010-01-01

    Vitamin D deficiency has been identified in many British children. This condition has many deleterious effects on their health. Taking vitamin D status into account needs to become a daily element of primary care practice, both in antenatal and postnatal situations. It is probable that a significant improvement in reducing chronic diseases in adulthood will result from a more proactive approach in children.

  16. GLUT-1 DEFICIENCY: FROM PATHOPHYSILOGY AND GENETICS TO ABROAD CLINICAL SPECTRUM

    Directory of Open Access Journals (Sweden)

    Arsov Todor

    2016-07-01

    Full Text Available The classical GLUT-1 deficiency syndrome (GLUT-1 DS, De Vivo disease was described over 2 decades ago as a metabolic encephalopathy characterized by developmental delay, secondary microcephaly paroxysmal neurological symptoms (epilepsy and movement disorders. The biochemical parameters of this disease, used in diagnosis, are low levels of glucose in the cerebrospinal fluid, normal level of glucose in the blood and consequent low ratio of cerebrospinal fluid vs. blood glucose levels (<40-45%. So far, more than 200 cases of the classical GLUT-1 DS have been described in the literature. Genetic research demonstrated that this disease is caused by mutations in SLC2A1 gene coding for GLUT-1, a transporter of glucose across the blood brain barrier. Over the last few years the clinical spectrum of GLUT-1 deficiencywas expanded to include other rare diseases such as paroxysmal exertional dyskinesia and early-onset absence epilepsy, but also some more common diseases such as idiopathic generalised epilepsy (1-2%. GLUT-1 deficiency is an important pathophysiological basis of these diseases as early diagnosis (aided by DNA mutation testing and treatment (ketogenic diet could lead to improved disease outcomes.

  17. Comparison of vitamin D deficiency and magnitude of severity of vitamin D deficiency in cirrhotic and non-cirrhotic patients with chronic hepatitis C in a tertiary care hospital Rawalpindi, Pakistan

    International Nuclear Information System (INIS)

    Hamid, S.; Faheem, M.; Ambreen, S.; Tirmizi, A.; Umar, M.

    2017-01-01

    Objective: To determine Vitamin D deficiency in both cirrhotic and non-cirrhotic patients with chronic hepatitis C (CHC). Methodology: We conducted a cross-sectional study at Centre for Liver and Digestive Diseases (CLD), Holy Family Hospital, Rawalpindi, Pakistan from August 2015 to February 2016 and included 120 Patients with CHC with or without cirrhosis. Two groups were formed and vitamin D levels were measured and level of severity was assessed. Results: Out of 120 patients, 94(78.3%) patients had Vitamin D deficiency. 63(100%) cirrhotic patients and 31 54.4%) non cirrhotic patients had Vitamin D deficiency. In cirrhotic patients, 26(41.3%) had mild and 36(58.7%) had moderate Vitamin D deficiency while in non-cirrhotic patients 25(43.9%) had mild and 6(10.5%) had moderate deficiency. No patient with severe Vitamin D deficiency was observed. Conclusion: Most of the patients infected with CHC suffer from vitamin D deficiency. This was observed more in cirrhotic patients than non-cirrhotic patients. Moreover, positive correlation was observed among vitamin D deficiency and stage of fibrosis. (author)

  18. Vitamin C and Vitamin E in Prevention of Nonalcoholic Fatty Liver Disease (NAFLD in Choline Deficient Diet Fed Rats

    Directory of Open Access Journals (Sweden)

    Lopasso Fabio P

    2003-10-01

    Full Text Available Abstract Aim Oxidative stress has been implicated in the pathogenesis of Nonalcoholic Fatty Liver Disease (NAFLD. Vitamin C and vitamin E are known to react with reactive oxygen species (ROS blocking the propagation of radical reactions in a wide range of oxidative stress situations. The potential therapeutic efficacy of antioxidants in NAFLD is unknown. The aim of this study was to evaluate the role of antioxidant drugs (vitamin C or vitamin E in its prevention. Methods Fatty liver disease was induced in Wistar rats by choline-deficient diet for four weeks. The rats were randomly assigned to receive vitamin E (n = 6 – (200 mg/day, vitamin C (n = 6 (30 mg/Kg/day or vehicle orally. Results In the vehicle and vitamin E-treated rats, there were moderate macro and microvesicular fatty changes in periportal area without inflammatory infiltrate or fibrosis. Scharlach stain that used for a more precise identification of fatty change was strong positive. With vitamin C, there was marked decrease in histological alterations. Essentially, there was no liver steatosis, only hepatocellular ballooning. Scharlach stain was negative. The lucigenin-enhanced luminescence was reduced with vitamin C (1080 ± 330 cpm/mg/minx103 as compared to those Vitamin E and control (2247 ± 790; 2020 ± 407 cpm/mg/minx103, respectively (p Conclusions 1 Vitamin C reduced oxidative stress and markedly inhibited the development of experimental liver steatosis induced by choline-deficient diet ; 2Vitamin E neither prevented the development of fatty liver nor reduced the oxidative stress in this model.

  19. How We Manage Adenosine Deaminase-Deficient Severe Combined Immune Deficiency (ADA SCID).

    Science.gov (United States)

    Kohn, Donald B; Gaspar, H Bobby

    2017-05-01

    Adenosine deaminase-deficient severe combined immune deficiency (ADA SCID) accounts for 10-15% of cases of human SCID. From what was once a uniformly fatal disease, the prognosis for infants with ADA SCID has improved greatly based on the development of multiple therapeutic options, coupled with more frequent early diagnosis due to implementation of newborn screening for SCID. We review the various treatment approaches for ADA SCID including allogeneic hematopoietic stem cell transplantation (HSCT) from a human leukocyte antigen-matched sibling or family member or from a matched unrelated donor or a haplo-identical donor, autologous HSCT with gene correction of the hematopoietic stem cells (gene therapy-GT), and enzyme replacement therapy (ERT) with polyethylene glycol-conjugated adenosine deaminase. Based on growing evidence of safety and efficacy from GT, we propose a treatment algorithm for patients with ADA SCID that recommends HSCT from a matched family donor, when available, as a first choice, followed by GT as the next option, with allogeneic HSCT from an unrelated or haplo-identical donor or long-term ERT as other options.

  20. Validation of the qi blood yin yang deficiency questionnaire on chronic fatigue.

    Science.gov (United States)

    Kim, Jihye; Ku, Boncho; Kim, Keun Ho

    2016-01-01

    Chronic fatigue (CF) reflects an imbalance of inter-organ functions or of the four essential physiological components qi, blood (xue), yin, and yang. CF can be subdivided into different patterns. However, there are no diagnostic methods for CF. This study aimed to clinically validate a pattern identification method by identifying correlations between CF and responses to the qi blood yin yang deficiency questionnaire (QBYY-Q). Participants were recruited between May and June 2014 through the Kyung Hee University Korean Medicine hospital website and via posters and comprised 129 CF patients diagnosed with the United States Centers for Disease Control and Prevention (1994) criteria. Participants who had organic diseases that explained the CF were excluded. A total of 159 participants were asked to complete the QBYY-Q, the fatigue severity scale, and the Chalder fatigue scale. The latter two questionnaires were used to assess convergent validity with the QBYY-Q. Among the 129 CF participants, 70 and 59 had chronic fatigue syndrome and idiopathic chronic fatigue, respectively. Two Korean medical doctors independently assessed participants' qi, blood, yin, and yang deficiency patterns using QBYY deficiency pattern identification guidelines. Based on the results of a preliminary study of the QBYY-Q, we selected 32 reliable items for symptoms corresponding to each deficiency pattern. The items were used to estimate internal consistency and construct validity. Multinomial logistic regression analysis was performed for scores on each deficiency pattern. The data were means and standard deviations or numbers of participants and proportions for continuous and categorical variables, respectively. A statistical significance level of P yin, and yang deficiency were 45.1, 58.0, 52.2, and 63.4 %, respectively. Each QBYY-Q deficiency score was positively associated with each corresponding deficiency pattern. Qi deficiency was used as a reference category. Odds ratios of blood, yin

  1. Iron Deficiency and Anemia Predict Mortality in Patients with Tuberculosis123

    Science.gov (United States)

    Isanaka, Sheila; Mugusi, Ferdinand; Urassa, Willy; Willett, Walter C.; Bosch, Ronald J.; Villamor, Eduardo; Spiegelman, Donna; Duggan, Christopher; Fawzi, Wafaie W.

    2012-01-01

    Many studies have documented a high prevalence of anemia among tuberculosis (TB) patients and anemia at TB diagnosis has been associated with an increased risk of death. However, little is known about the factors contributing to the development of TB-associated anemia and their importance in TB disease progression. Data from a randomized clinical trial of micronutrient supplementation in patients with pulmonary TB in Tanzania were analyzed. Repeated measures of anemia with iron deficiency, anemia without iron deficiency, and iron deficiency without anemia were assessed as risk factors for treatment failure, TB recurrence, and mortality. The prevalence of anemia (hemoglobin iron deficiency (mean corpuscular volume , 80 fL). We found no evidence of an association between anemia (with or without iron deficiency) or iron deficiency without anemia at baseline and the risk of treatment failure at 1 mo after initiation. Anemia without iron deficiency was associated with an independent, 4-fold increased risk of TB recurrence [adjusted RR = 4.10 (95% CI = 1.88, 8.91); P Iron deficiency and anemia (with and without iron deficiency) were associated with a 2- to nearly 3-fold independent increase in the risk of death [adjusted RR for iron deficiency without anemia = 2.89 (95% CI = 1.53, 5.47); P = 0.001; anemia without iron deficiency = 2.72 (95% CI = 1.50, 4.93); P = 0.001; iron deficiency anemia = 2.13 (95% CI = 1.10, 4.11); P = 0.02]. Efforts to identify and address the conditions contributing to TB-associated anemia, including iron deficiency, could play an important role in reducing morbidity and mortality in areas heavily affected by TB. PMID:22190024

  2. Tuberculosis and the acquired immune deficiency syndrome in South Brazil

    International Nuclear Information System (INIS)

    Vieira, M.V.; Genro, C.H.; Santos Silveira, R. de C. dos

    1989-01-01

    Tuberculosis and the acquired immune deficiency syndrome in South Brazil. The authors studied the incidence of tuberculosis in South Brazilian patients with acquired immune deficiency syndrome from January 1985 to June 1988. During this period, tuberculosis occurred in 10.3% of acquired immune deficiency syndrome patients. The socioeconomic conditions and the incidence of disease in the population were not confirmed as a potential risk for tuberculosis infection. Chest radiographs revealed pulmonary infiltrates in six patients, hilar and/or mediastinal adenopathy in three, and pleural effusion in two. The two remaining patients had pulmonary consolidation associated with other features. None of these patients presented pulmonary cavitation or radiographic findings of typical reactivation of pulmonary tuberculosis. (author) [pt

  3. Prevalence of glucose-6-phosphate dehydrogenase deficiency in ...

    African Journals Online (AJOL)

    Background: Glucose-6-phosphate dehydrogenase (G6PD) is a house keeping enzyme which catalyzes the first step in the hexose monophosphate pathway of glucose metabolism. G6PD deficiency is the commonest hemolytic X-linked genetic disease, which affects approximately 400 million people worldwide.

  4. Clinical Aspects of Trace Elements: Zinc in Human Nutrition – Zinc Deficiency and Toxicity

    Directory of Open Access Journals (Sweden)

    Michelle M Pluhator

    1996-01-01

    Full Text Available Available evidence suggests that trace elements, such as zinc, once thought to have no nutritional relevance, are possibly deficient in large sections of the human population. Conditioned deficiencies have been reported to result from malabsorption syndromes, acrodermatitis enteropathica, alcoholism, gastrointestinal disease, thermal injury, chronic diseases (eg, diabetes, sickle cell anemia, and in total parenteral nutrition therapy. Awareness that patients with these problems are at risk has led health professionals to focus increasingly on the importance of zinc therapy in the prevention and treatment of deficiency. More recently zinc toxicity and its role in human nutrition and well-being have come under investigation. Reports have focused on the role of zinc toxicity in causes of copper deficiency, changes in the immune system and alterations in blood lipids. As the numerous challenges presented by the study of zinc in human nutrition are met, more appropriate recommendations for dietary and therapeutic zinc intake are being made.

  5. Glucose-6-phosphate dehydrogenase deficiency in Nigerian children.

    Directory of Open Access Journals (Sweden)

    Olatundun Williams

    Full Text Available Glucose-6-phosphate dehydrogenase (G6PD deficiency is the most common human enzymopathy and in Sub-Saharan Africa, is a significant cause of infection- and drug-induced hemolysis and neonatal jaundice. Our goals were to determine the prevalence of G6PD deficiency among Nigerian children of different ethnic backgrounds and to identify predictors of G6PD deficiency by analyzing vital signs and hematocrit and by asking screening questions about symptoms of hemolysis. We studied 1,122 children (561 males and 561 females aged 1 month to 15 years. The mean age was 7.4 ± 3.2 years. Children of Yoruba ethnicity made up the largest group (77.5% followed by those Igbo descent (10.6% and those of Igede (10.2% and Tiv (1.8% ethnicity. G6PD status was determined using the fluorescent spot method. We found that the overall prevalence of G6PD deficiency was 15.3% (24.1% in males, 6.6% in females. Yoruba children had a higher prevalence (16.9% than Igede (10.5%, Igbo (10.1% and Tiv (5.0% children. The odds of G6PD deficiency were 0.38 times as high in Igbo children compared to Yoruba children (p=0.0500. The odds for Igede and Tiv children were not significantly different from Yoruba children (p=0.7528 and 0.9789 respectively. Mean oxygen saturation, heart rate and hematocrit were not significantly different in G6PD deficient and G6PD sufficient children. The odds of being G6PD deficient were 2.1 times higher in children with scleral icterus than those without (p=0.0351. In conclusion, we determined the prevalence of G6PD deficiency in Nigerian sub-populations. The odds of G6PD deficiency were decreased in Igbo children compared to Yoruba children. There was no association between vital parameters or hematocrit and G6PD deficiency. We found that a history of scleral icterus may increase the odds of G6PD deficiency, but we did not exclude other common causes of icterus such as sickle cell disease or malarial infection.

  6. Diagnosis of thalassemia and iron deficiency anemia using confocal and atomic force microscopy

    Science.gov (United States)

    Tariq, Saira; Bilal, Muhammad; Shahzad, Shaheen; Firdous, Shamaraz; Aziz, Uzma; Ahmed, Mushtaq

    2017-11-01

    Anemia is the most prevalent blood disorder, categorized into thalassemia and iron deficiency anemia. In anemia, the morphology of erythrocytes is disturbed, thus leading to abnormal functioning of the erythrocytes. Globally, thalassemia affects 1.3% of individuals and is one of the most widespread monogenic disorders in Pakistan. All over the World, women and children are most frequently affected by a type of nutritional deficiency known as iron deficiency anemia. The morphological changes that occur in erythrocytes due to these diseases are investigated in this study at the nano-scale level. Fifty samples of blood from individuals suffering from thalassemia or iron deficiency anemia were obtained from different hospitals in Rawalpindi and Islamabad. The blood samples were scanned using atomic force microscopy (AFM) and laser scanning confocal microscopy (LSCM) to check the morphological changes in both types of anemia. According to the present study, thalassemia is most prevalent in females in the age group between 5 and 15 years old, and iron deficiency is most prevalent in females in the age groups of 16-25 and 36-45 years old. Erythrocyte morphology is the significant determinant for diagnosing and discriminating between these two types of diseases. The study reports deformed erythrocytes in anemic patients, which were different from the ones that existed in the control. Thalassemia erythrocytes showed a crenated shape, iron deficiency anemia erythrocytes showed an elliptocyte shape and healthy erythrocytes showed a biconcave disk shape when using AFM and LSCM. These techniques seem to be very promising, cheap and less time consuming in determining the structure-function relationship of erythrocytes of thalassemic and iron deficiency anemic patients. The results of LSCM and AFM are quite useful in determining the morphological changes in erythrocytes and to study the disease at the molecular level within short period of time. Hence, we encourage employing

  7. Different patterns of {sup 123}I-BMIPP myocardial accumulation in patients with type I and II CD36 deficiency

    Energy Technology Data Exchange (ETDEWEB)

    Watanabe, Kenichi; Nagatomo, Takafumi [Niigata Coll. of Pharmacy (Japan); Toba, Ken; Ogawa, Yusuke; Aizawa, Yoshifusa; Tanabe, Naohito; Miyajima, Seiichi; Kusano, Yoriko; Hirokawa, Yoichi

    1997-12-01

    The CD36 molecule is a multifunctional membrane type receptor glycoprotein that reacts with thrombospondin, collagen, oxidized LDL and long-chain fatty acids (LCFA). LCFA are one of the major cardiac energy substrates, hence LCFA metabolism may have an important role in cardiac diseases. In this study, we analyzed CD36 expression in 200 patients with heart diseases (44 patients with hypertrophic cardiomyopathy (HCM), 16 with dilated cardiomyopathy (DCM), 26 with old myocardial infarction (OMI), 55 with angina pectoris (AP) and 59 with other miscellaneous heart diseases) using a flow cytometer. {sup 123}I-{beta}-methyl-p-iodophenylpentadecanoic acid (BMIPP) myocardial accumulation was also examined in some patients. Eight patients (2 with HCM, 1 with DCM, 2 with OMI, and 3 with AP) were diagnosed as having type I CD36 deficiency (neither platelets nor monocytes expressed CD36). Sixteen patients (3 with HCM, 1 with DCM, 1 with OMI, 8 with AP, and 3 with other heart diseases) showed type II CD36 deficiency (monocytes expressed CD36 but platelets did not). In all 8 patients with type I CD36 deficiency, there was no BMIPP accumulation in the heart. However, in 13 patients with type II CD36 deficiency, focally reduced BMIPP accumulation was observed, but there were no patients without BMIPP accumulation. CD36 deficiency was observed in a higher proportion (12%) of patients with heart disease in this study than in a reported control study. Type I CD36 deficiency is associated with absence of BMIPP accumulation in the heart, hence it may have an important role in LCFA metabolic disorders and some types of cardiac hypertrophy as well as other heart diseases. (author)

  8. IS THERE A LINK BETWEEN SUNLIGHT EXPOSURE AND 25-HYDROXYVITAMIN D DEFICIENCY IN CHRONIC KIDNEY DISEASE PATIENTS?

    Directory of Open Access Journals (Sweden)

    Angela Yee-Moon Wang

    2012-06-01

    In conclusion, our study confirmed an extremely high prevalence of vitamin D deficiency and an important association between outdoor sunlight exposure and 25(OHD deficiency in Chinese stage 3-5 CKD patients. Further study is needed to determine whether increasing daily outdoor sunlight exposure may represent a cost-free treatment for correcting nutritional 25(OHD deficiency in the CKD population.

  9. Deficient Rab11 activity underlies glucose hypometabolism in primary neurons of Huntington's disease mice

    Energy Technology Data Exchange (ETDEWEB)

    Li, Xueyi, E-mail: xli12@partners.org [Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129 (United States); Valencia, Antonio; McClory, Hollis; Sapp, Ellen; Kegel, Kimberly B. [Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129 (United States); DiFiglia, Marian, E-mail: difiglia@helix.mgh.harvard.edu [Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129 (United States)

    2012-05-18

    Highlights: Black-Right-Pointing-Pointer Primary Huntington's disease neurons are impaired in taking up glucose. Black-Right-Pointing-Pointer Rab11 modulates glucose uptake in neurons. Black-Right-Pointing-Pointer Increasing Rab11 activity attenuates the glucose uptake defect in disease neurons. Black-Right-Pointing-Pointer We provide a novel mechanism for glucose hypometabolism in Huntington's disease. -- Abstract: Huntington's disease (HD) is a progressive neurodegenerative disorder caused by a CAG repeat expansion in the huntingtin gene. Positron emission tomography studies have revealed a decline in glucose metabolism in the brain of patients with HD by a mechanism that has not been established. We examined glucose utilization in embryonic primary cortical neurons of wild-type (WT) and HD knock-in mice, which have 140 CAG repeats inserted in the endogenous mouse huntingtin gene (HD{sup 140Q/140Q}). Primary HD{sup 140Q/140Q} cortical neurons took up significantly less glucose than did WT neurons. Expression of permanently inactive and permanently active forms of Rab11 correspondingly altered glucose uptake in WT neurons, suggesting that normal activity of Rab11 is needed for neuronal uptake of glucose. It is known that Rab11 activity is diminished in HD{sup 140Q/140Q} neurons. Expression of dominant active Rab11 to enhance the activity of Rab11 normalized glucose uptake in HD{sup 140Q/140Q} neurons. These results suggest that deficient activity of Rab11 is a novel mechanism for glucose hypometabolism in HD.

  10. Deficiências minerais nas fôlhas induzidas por moléstias e pragas Leaf deficiencies associated with virus infection or insect toxin

    Directory of Open Access Journals (Sweden)

    A. S. Costa

    1965-01-01

    Full Text Available Certas moléstias de vírus e o efeito fitotóxico provocado por toxinas de alguns insetos influenciam a composição mineral das fôlhas de plantas afetadas. As alterações provocadas podem se assemelhar a deficiências minerais puramente nutricionais e, em certos casos, há realmente menor teor do elemento associado aos sintomas da moléstia. A aplicação do elemento faltante nos casos citados não provoca geralmente recuperação dos tecidos afetados, com exceção da deficiência de zinco associada à infecção de citros pela tristeza. É sugerido que a resposta à aplicação do elemento em deficiência dependerá de ser ou não esta, sintoma primário ou secundário da moléstia. É salientado que as recomendações sôbre adubação, baseadas nos resultados da diagnose foliar, deverão sempre considerar a possibilidade de não serem as deficiências constatadas resultantes sempre da falta de disponibilidade do elemento no solo, mas, possivelmente, da interferência de fatôres como a infecção por vírus, ação de toxina de inseto etc.Virus diseases or the toxicogenic effect induced by insect feeding influence the mineral content of affected plants. Some of the changes induced result in leaf deficiencies similar to those associated with lack of the available element in the soil. Application of the lacking element in most cases does not promote a favorable response with exception of the zinc deficiency associated with tristeza infection in citrus. It is suggested that the negative or positive response might depend on the symptom being primary or secondary. It is pointed out that fertilizer recommendations based on foliar diagnosis should always take into consideration that the deficiencies encountered are not necessarily theresult of lack of the available element in thesoil, but sometimes of the interference of virus diseases, insect toxins, and other factors.

  11. Deficiência de ferro no feto e no recém-nascido Iron deficiency in the fetus and newborn

    Directory of Open Access Journals (Sweden)

    Maria Renata T. Chopard

    2010-06-01

    Full Text Available A principal causa de anemia no feto é a doença hemolítica do recém-nascido (RN. As gestantes anêmicas na sua forma moderada não acarretam baixos estoques de ferro no concepto, porém podem evoluir para o trabalho de parto prematuro e RN com baixo peso ao nascer. O ferro é transportado para o feto por via transplacentária, principalmente durante o terceiro trimestre de gestação. A deficiência de ferro não ocorre no período neonatal, porém os prematuros e ou RN com baixo peso constituem o principal grupo de risco para desenvolver a deficiência de ferro. Nos RN nascidos a termo podemos observar uma deficiência de ferro naqueles que sofreram ressecção cirúrgica do duodeno devido à malformação congênita. A fim de evitarmos a deficiência de ferro neste grupo de risco, indica-se a suplementação de ferro a partir dos 30 dias de vida. A via de administração preferencial é a enteral, apesar de sabermos que no prematuro ocorre uma deficiência do controle da absorção do ferro. O complexo de ferro polimaltosado e o ferro aminoquelado são os de escolha para a profilaxia da deficiência de ferro em prematuros. A via endovenosa é segura e não acarreta piora das lesões causadas pela ação oxidativa do ferro em prematuros.The main cause of anemia in the fetus is hemolytic disease. Mildly anemic pregnant women may evolve with premature labor and have low birth weight babies, but the baby's iron status is not influenced by the mother's iron deficiency. Iron transportation through the placenta occurs in the third trimester of gestation and premature labor results in reduced iron stores. Iron deficiency anemia does not occur during the neonatal period, but premature and low birth weight babies are at risk of developing iron deficiency. In full-term babies iron deficiency can occur due to intestinal malformation that leads to duodenal resection. To avoid iron deficiency in at-risk babies, iron supplementation is recommended from

  12. Prevalence of vitamin D deficiency and rickets in children with cholestasis in Iran.

    Science.gov (United States)

    Mohammadi, Bahram; Najafi, Mehri; Farahmand, Fateme; Motamed, Farzaneh; Ghajarzadeh, Mahsa; Mohammadi, Jamshid; Eshagh Roze, Mohammad

    2012-01-01

    This study was aimed to determine prevalence of vitamin D deficiency and rickets in children with cholestatic liver diseases. Forty eight children with established cholestatic liver disease who referred to gastrointestinal clinic of Children Medical Center (Tehran, Iran) between April 2010 and March 2011 were enrolled in a cross-sectional study. Laboratory analysis including calcium, phosphate, albumin, total and direct bilirubin, aminotransferases, alkalinephosphatase (ALP), prothrombin time (PT), parathyroid hormone (PTH), total protein determined by routine laboratory techniques. Mean age of participants was 299.1 ± 676.8 days (range 2-3600 days) whereas twenty one were female (43.8%) and 27 (56.3%) were male. Twenty two (45.8%) had evidences of rickets in X-ray evaluation. Three children with rickets and two with normal X-ray had vitamin D deficiency while ten in rickets group and 16 in normal group had vitamin D insufficiency. The main underlying diseases were anatomical biliary atresia in cases with rickets and idiopathic in other group. Rickets and vitamin D deficiency should be considered in chronic cholestatic children.

  13. Hematopoietic sphingosine 1-phosphate lyase deficiency decreases atherosclerotic lesion development in LDL-receptor deficient mice.

    Directory of Open Access Journals (Sweden)

    Martine Bot

    Full Text Available AIMS: Altered sphingosine 1-phosphate (S1P homeostasis and signaling is implicated in various inflammatory diseases including atherosclerosis. As S1P levels are tightly controlled by S1P lyase, we investigated the impact of hematopoietic S1P lyase (Sgpl1(-/- deficiency on leukocyte subsets relevant to atherosclerosis. METHODS AND RESULTS: LDL receptor deficient mice that were transplanted with Sgpl1(-/- bone marrow showed disrupted S1P gradients translating into lymphopenia and abrogated lymphocyte mitogenic and cytokine response as compared to controls. Remarkably however, Sgpl1(-/- chimeras displayed mild monocytosis, due to impeded stromal retention and myelopoiesis, and plasma cytokine and macrophage expression patterns, that were largely compatible with classical macrophage activation. Collectively these two phenotypic features of Sgpl1 deficiency culminated in diminished atherogenic response. CONCLUSIONS: Here we not only firmly establish the critical role of hematopoietic S1P lyase in controlling S1P levels and T cell trafficking in blood and lymphoid tissue, but also identify leukocyte Sgpl1 as critical factor in monocyte macrophage differentiation and function. Its, partly counterbalancing, pro- and anti-inflammatory activity spectrum imply that intervention in S1P lyase function in inflammatory disorders such as atherosclerosis should be considered with caution.

  14. Molecular analysis of carnitine palmitoyltransferase II deficiency with hepatocardiomuscular expression

    Energy Technology Data Exchange (ETDEWEB)

    Bonnefont, J.P.; Cepanec, C.; Leroux, J.P. [Unite INSERM, Paris (France)] [and others

    1996-05-01

    Carnitine palmitoyltransferase (CPT) II deficiency, an inherited disorder of mitochondrial long-chain fatty-acid (LCFA) oxidation, results in two distinct clinical act phenotypes, namely, an adult (muscular) form and an infantile (hepatocardiomuscular) form. The rationale of this phenotypic heterogeneity is poorly understood. The adult form of the disease is commonly ascribed to the Ser-113-Leu substitution in CPT II. Only few data are available regarding the molecular basis of the infantile form of the disease. We report herein a homozygous A-2399-C transversion predicting a Tyr-628-Ser substitution in a CPT II-deficient infant. In vitro expression of mutant cDNA in COS-1 cells demonstrated the responsibility of this mutation for the disease. Metabolic consequences of the Ser-113-Leu and Tyr-628-Ser substitutions were studied in fibroblasts. The Tyr-628-Ser substitution (infantile form) resulted in a 10% CPT II residual activity, markedly impairing LCFA oxidation, whereas the Ser-113-Leu substitution (adult form) resulted in a 20% CPT II residual activity, without consequence on LCFA oxidation. These data show that CPT II activity has to be reduced below a critical threshold in order for LCFA oxidation in fibroblasts to be impaired. The hypothesis that this critical threshold differs among tissues could provide a basis to explain phenotypic heterogeneity of CPT II deficiency. 32 refs., 5 figs.

  15. 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).

  16. There is chronic latent magnesium deficiency in apparently healthy university students

    OpenAIRE

    Hermes Sales, Cristiane; Azevedo Nascimento, Débora; Queiroz Medeiros, Anna Cecília; Costa Lima, Kênio; Campos Pedrosa, Lucia Fátima; Colli, Célia

    2014-01-01

    Introduction: Magnesium is an essential micronutrient for human body, and its deficiency has been associated with risk of non-communicable diseases. Objective: Assessment of magnesium status, and evaluation of the frequency of magnesium deficiency in a group of healthy adults. Methods: Plasma and erythrocyte magnesium levels, and magnesium intake were determined in 115 students (55 women and 60 men), from a public university in Brazil. Results: The medians of magnesium concentration in plasma...

  17. Liver and Skin Histopathology in Adults with Acid Sphingomyelinase Deficiency (Niemann-Pick Disease Type B)

    Science.gov (United States)

    Thurberg, Beth L.; Wasserstein, Melissa P.; Schiano, Thomas; O’Brien, Fanny; Richards, Susan; Cox, Gerald F.; McGovern, Margaret M.

    2012-01-01

    Acid sphingomyelinase deficiency (ASMD) is a lysosomal storage disorder characterized by the pathologic accumulation of sphingomyelin in multiple cells types, and occurs most prominently within the liver, spleen and lungs, leading to significant clinical disease. Seventeen ASMD patients underwent a liver biopsy during baseline screening for a Phase 1 trial of recombinant human acid sphingomyelinase (rhASM) in adults with Niemann-Pick disease type B. Eleven of the 17 were enrolled in the trial and each received a single dose of rhASM and underwent a repeat liver biopsy on Day 14. Biopsies were evaluated for fibrosis, sphingomyelin accumulation and macrophage infiltration by light and electron microscopy. When present, fibrosis was periportal and pericellular, predominantly surrounding affected Kupffer cells. Two baseline biopsies exhibited frank cirrhosis. Sphingomyelin was localized to isolated Kupffer cells in mildly affected biopsies and was present in both Kupffer cells and hepatocytes in more severely affected cases. Morphometric quantification of sphingomyelin storage in liver biopsies ranged from 4–44% of the microscopic field. Skin biopsies were also performed at baseline and Day 14 in order to compare the sphingomyelin distribution in a peripheral tissue to that of liver. Sphingomyelin storage was present at lower levels in multiple cell types of the skin, including dermal fibroblasts, macrophages, vascular endothelial cells, vascular smooth muscle cells and Schwann cells. This Phase 1 trial of rhASM in adults with ASMD provided a unique opportunity for a prospective assessment of hepatic and skin pathology in this rare disease and their potential usage as pharmacodynamic biomarkers. PMID:22613999

  18. Sick sinus syndrome in HCN1-deficient mice.

    Science.gov (United States)

    Fenske, Stefanie; Krause, Stefanie C; Hassan, Sami I H; Becirovic, Elvir; Auer, Franziska; Bernard, Rebekka; Kupatt, Christian; Lange, Philipp; Ziegler, Tilman; Wotjak, Carsten T; Zhang, Henggui; Hammelmann, Verena; Paparizos, Christos; Biel, Martin; Wahl-Schott, Christian A

    2013-12-17

    Sinus node dysfunction (SND) is a major clinically relevant disease that is associated with sudden cardiac death and requires surgical implantation of electric pacemaker devices. Frequently, SND occurs in heart failure and hypertension, conditions that lead to electric instability of the heart. Although the pathologies of acquired SND have been studied extensively, little is known about the molecular and cellular mechanisms that cause congenital SND. Here, we show that the HCN1 protein is highly expressed in the sinoatrial node and is colocalized with HCN4, the main sinoatrial pacemaker channel isoform. To characterize the cardiac phenotype of HCN1-deficient mice, a detailed functional characterization of pacemaker mechanisms in single isolated sinoatrial node cells, explanted beating sinoatrial node preparation, telemetric in vivo electrocardiography, echocardiography, and in vivo electrophysiology was performed. On the basis of these experiments we demonstrate that mice lacking the pacemaker channel HCN1 display congenital SND characterized by bradycardia, sinus dysrhythmia, prolonged sinoatrial node recovery time, increased sinoatrial conduction time, and recurrent sinus pauses. As a consequence of SND, HCN1-deficient mice display a severely reduced cardiac output. We propose that HCN1 stabilizes the leading pacemaker region within the sinoatrial node and hence is crucial for stable heart rate and regular beat-to-beat variation. Furthermore, we suggest that HCN1-deficient mice may be a valuable genetic disease model for human SND.

  19. 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 ...

  20. Autosomal recessive inheritance of GLUT1 deficiency syndrome.

    NARCIS (Netherlands)

    Klepper, J.; Scheffer, H.; Elsaid, M.F.; Kamsteeg, E.J.; Leferink, M.; Ben-Omran, T.

    2009-01-01

    GLUT1 deficiency syndrome (GLUT1DS) is understood as a monogenetic disease caused by heterozygous SLC2A1 gene mutations with autosomaldominant and sporadic transmission. We report on a six-year-old girl from an inbred Arab family with moderate global developmental delay, epilepsy, ataxia, hypotonia,

  1. Is muscle glycogenolysis impaired in X-linked phosphorylase b kinase deficiency?

    DEFF Research Database (Denmark)

    Orngreen, M.C.; Schelhaas, H.J.; Jeppesen, T.D.

    2008-01-01

    OBJECTIVE: It is unclear to what extent muscle phosphorylase b kinase (PHK) deficiency is associated with exercise-related symptoms and impaired muscle metabolism, because 1) only four patients have been characterized at the molecular level, 2) reported symptoms have been nonspecific, and 3......) lactate responses to ischemic handgrip exercise have been normal. METHODS: We studied a 50-year-old man with X-linked PHK deficiency using ischemic forearm and cycle ergometry exercise tests to define the derangement of muscle metabolism. We compared our findings with those in patients with Mc...... in healthy subjects. Constant workload elicited a second wind in all patients with McArdle disease, but not in the patient with PHK deficiency. IV glucose administration appeared to improve exercise tolerance in the patient with PHK deficiency, but not to the same extent as in the patients with Mc...

  2. Intravenous augmentation treatment and lung density in severe α1 antitrypsin deficiency (RAPID)

    DEFF Research Database (Denmark)

    Chapman, Kenneth R; Burdon, Jonathan G W; Piitulainen, Eeva

    2015-01-01

    BACKGROUND: The efficacy of α1 proteinase inhibitor (A1PI) augmentation treatment for α1 antitrypsin deficiency has not been substantiated by a randomised, placebo-controlled trial. CT-measured lung density is a more sensitive measure of disease progression in α1 antitrypsin deficiency emphysema...... of emphysema, a finding that could not be substantiated by lung density measurement at FRC alone or by the two measurements combined. These findings should prompt consideration of augmentation treatment to preserve lung parenchyma in individuals with emphysema secondary to severe α1 antitrypsin deficiency...

  3. MAPK Phosphatase-1 Deficiency Exacerbates the Severity of Imiquimod-Induced Psoriasiform Skin Disease

    Directory of Open Access Journals (Sweden)

    Weiheng Zhao

    2018-03-01

    Full Text Available Persistent activation of mitogen-activated protein kinase (MAPK is believed to be involved in psoriasis pathogenesis. MAPK phosphatase-1 (MKP-1 is an important negative regulator of MAPK activity, but the cellular and molecular mechanisms of MKP-1 in psoriasis development are largely unknown. In this study, we found that the expression of MKP-1 was decreased in the imiquimod (IMQ-induced psoriasiform mouse skin. MKP-1-deficient (MKP-1−/− mice were highly susceptible to IMQ-induced skin inflammation, which was associated with increased production of inflammatory cytokines and chemokines. MKP-1 acted on both hematopoietic and non-hematopoietic cells to regulate psoriasis pathogenesis. MKP-1 deficiency in macrophages led to enhanced p38 activation and higher expression of interleukin (IL-1β, CXCL2, and S100a8 upon R848 stimulation. Moreover, MKP-1 deficiency in the non-hematopoietic compartments led to an enhanced IL-22 receptor signaling and higher expression of CXCL1 and CXCL2 upon IMQ treatment. Collectively, our data suggest a critical role for MKP-1 in the regulation of skin inflammation.

  4. Epstein-Barr virus myelitis and Castleman's disease in a patient with acquired immune deficiency syndrome: a case report

    Directory of Open Access Journals (Sweden)

    Balderacchi Jasminka

    2011-05-01

    Full Text Available Abstract Introduction Few cases of Epstein-Barr virus myelitis have been described in the literature. Multi-centric Castleman's disease is a lymphoproliferative disorder that is well known for its associations with the human immunodeficiency virus, human herpes virus 8, and Kaposi's sarcoma. The concurrent presentation of these two diseases in a patient at the same time is extremely unusual. Case Presentation We describe the case of a 43-year-old Caucasian man with acquired immune deficiency syndrome who presented with fever, weight loss and diffuse lymphadenopathy, and was diagnosed with multi-centric Castleman's disease. He presented three weeks later with lower extremity weakness and urinary retention, at which time cerebrospinal fluid contained lymphocytic pleocytosis and elevated protein. Magnetic resonance imaging demonstrated abnormal spinal cord signal intensity over several cervical and thoracic segments, suggesting the diagnosis of myelitis. Our patient was ultimately diagnosed with Epstein-Barr virus myelitis, as Epstein-Barr virus DNA was detected by polymerase chain reaction in the cerebrospinal fluid. Conclusion To the best of our knowledge, this is the first case of multi-centric Castleman's disease followed by acute Epstein-Barr virus myelitis in a human immunodeficiency virus-infected patient. Clinicians caring for human immunodeficiency virus-infected patients should be vigilant about monitoring patients with increasing lymphadenopathy, prompting thorough diagnostic investigations when necessary.

  5. Renal AA amyloidosis in a patient with hereditary complete complement C4 deficiency

    Directory of Open Access Journals (Sweden)

    Imed Helal

    2011-01-01

    Full Text Available Hereditary complete C4 deficiency has until now been reported in 30 cases only. A disturbed clearance of immune- complexes probably predisposes these individuals to systemic lupus erythematosus, other immune- complex diseases and recurrent microbial infections. We present here a 20- year- old female with hereditary complete C4 deficiency. Renal biopsy demonstrated renal AA amyloidosis. This unique case further substantiates that deficiency of classical pathway components predisposes to the development of recurrent microbial infections and that the patients may develop AA amyloidosis. Furthermore, in clinical practice, the nephrotic syndrome occurring in a patient with hereditary complete complement C4 deficiency should lead to the suspicion of renal AA amyloidosis.

  6. Obesity as an Emerging Risk Factor for Iron Deficiency

    Directory of Open Access Journals (Sweden)

    Elmar Aigner

    2014-09-01

    Full Text Available Iron homeostasis is affected by obesity and obesity-related insulin resistance in a many-facetted fashion. On one hand, iron deficiency and anemia are frequent findings in subjects with progressed stages of obesity. This phenomenon has been well studied in obese adolescents, women and subjects undergoing bariatric surgery. On the other hand, hyperferritinemia with normal or mildly elevated transferrin saturation is observed in approximately one-third of patients with metabolic syndrome (MetS or nonalcoholic fatty liver disease (NAFLD. This constellation has been named the “dysmetabolic iron overload syndrome (DIOS”. Both elevated body iron stores and iron deficiency are detrimental to health and to the course of obesity-related conditions. Iron deficiency and anemia may impair mitochondrial and cellular energy homeostasis and further increase inactivity and fatigue of obese subjects. Obesity-associated inflammation is tightly linked to iron deficiency and involves impaired duodenal iron absorption associated with low expression of duodenal ferroportin (FPN along with elevated hepcidin concentrations. This review summarizes the current understanding of the dysregulation of iron homeostasis in obesity.

  7. Choline Deficiency Causes Colonic Type II Natural Killer T (NKT) Cell Loss and Alleviates Murine Colitis under Type I NKT Cell Deficiency.

    Science.gov (United States)

    Sagami, Shintaro; Ueno, Yoshitaka; Tanaka, Shinji; Fujita, Akira; Niitsu, Hiroaki; Hayashi, Ryohei; Hyogo, Hideyuki; Hinoi, Takao; Kitadai, Yasuhiko; Chayama, Kazuaki

    2017-01-01

    Serum levels of choline and its derivatives are lower in patients with inflammatory bowel disease (IBD) than in healthy individuals. However, the effect of choline deficiency on the severity of colitis has not been investigated. In the present study, we investigated the role of choline deficiency in dextran sulfate sodium (DSS)-induced colitis in mice. Methionine-choline-deficient (MCD) diet lowered the levels of type II natural killer T (NKT) cells in the colonic lamina propria, peritoneal cavity, and mesenteric lymph nodes, and increased the levels of type II NKT cells in the livers of wild-type B6 mice compared with that in mice fed a control (CTR) diet. The gene expression pattern of the chemokine receptor CXCR6, which promotes NKT cell accumulation, varied between colon and liver in a manner dependent on the changes in the type II NKT cell levels. To examine the role of type II NKT cells in colitis under choline-deficient conditions, we assessed the severity of DSS-induced colitis in type I NKT cell-deficient (Jα18-/-) or type I and type II NKT cell-deficient (CD1d-/-) mice fed the MCD or CTR diets. The MCD diet led to amelioration of inflammation, decreases in interferon (IFN)-γ and interleukin (IL)-4 secretion, and a decrease in the number of IFN-γ and IL-4-producing NKT cells in Jα18-/- mice but not in CD1d-/- mice. Finally, adaptive transfer of lymphocytes with type II NKT cells exacerbated DSS-induced colitis in Jα18-/- mice with MCD diet. These results suggest that choline deficiency causes proinflammatory type II NKT cell loss and alleviates DSS-induced colitis. Thus, inflammation in DSS-induced colitis under choline deficiency is caused by type II NKT cell-dependent mechanisms, including decreased type II NKT cell and proinflammatory cytokine levels.

  8. Selenium deficiency-induced alterations in ion profiles in chicken muscle.

    Directory of Open Access Journals (Sweden)

    Haidong Yao

    Full Text Available Ion homeostasis plays important roles in development of metabolic diseases. In the present study, we examined the contents and distributions of 25 ions in chicken muscles following treatment with selenium (Se deficiency for 25 days. The results revealed that in chicken muscles, the top ranked microelements were silicon (Si, iron (Fe, zinc (Zn, aluminum (Al, copper (Cu and boron (B, showing low contents that varied from 292.89 ppb to 100.27 ppm. After Se deficiency treatment, essential microelements [Cu, chromium (Cr, vanadium (V and manganese (Mn], and toxic microelements [cadmium (Cd and mercury (Hg] became more concentrated (P < 0.05. Elements distribution images showed generalized accumulation of barium (Ba, cobalt (Co, Cu, Fe and V, while Cr, Mn, and Zn showed pin point accumulations in muscle sections. Thus, the ion profiles were generally influenced by Se deficiency, which suggested a possible role of Se deficiency in muscle dysfunctions caused by these altered ion profiles.

  9. 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 ...

  10. Iron-Deficiency Anemia

    Medline Plus

    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 ...

  11. Bipolar and Related Disorders Induced by Sodium 4-Phenylbutyrate in a Male Adolescent with Bile Salt Export Pump Deficiency Disease.

    Science.gov (United States)

    Vitale, Giovanni; Simonetti, Giulia; Pirillo, Martina; Taruschio, Gianfranco; Andreone, Pietro

    2016-09-01

    Bile Salt Export Pump (BSEP) Deficiency disease, including Progressive Familial Intrahepatic Cholestasis type 2 (PFIC2), is a rare disease, usually leading within the first ten years to portal hypertension, liver failure, hepatocellular carcinoma. Often liver transplantation is needed. Sodium 4-phenylbutyrate (4-PB) seems to be a potential therapeutic compound for PFIC2. Psychiatric side effects in the adolescent population are little known and little studied since the drug used to treat children and infants. So we described a case of Caucasian boy, suffering from a late onset PFIC2, listed for a liver transplant when he was sixteen and treated with 4-FB (200 mg per kilogram of body weight per day). The drug was discontinued for the onset of bipolar and related disorders. This case illustrates possible psychiatric side effects of the drug.

  12. 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 ...

  13. A case report: Familial glucocorticoid deficiency associated with familial focal segmental glomerulosclerosis

    Directory of Open Access Journals (Sweden)

    Ram Nanik

    2012-12-01

    Full Text Available Abstract Background Familial glucocorticoid deficiency (FGD is a rare autosomal recessive disorder characterized by isolated glucocorticoid deficiency in the presence of normal plasma renin and aldosterone level. Focal segmental glomerulosclerosis (FSGS is a form of glomerular disease associated with proteinuria and nephritic syndrome. This is the first case of familial glucocorticoid deficiency associated with familial focal segmental glomerulosclerosis. Case presentation An eight month old boy presented with increased genital pigmentation. Initial investigation revealed that he was glucocorticoid deficient and was started on hydrocortisone and fludrocortisone with a diagnosis of primary adrenal insufficiency. Later fludrocortisone was withdrawn and he was diagnosed to have isolated glucocorticoid deficiency. He later developed focal segmental glomerulosclerosis for which he underwent renal transplantation at the age of five years. Now at the age of twelve years, this boy is doing well on hydrocortisone treatment. His two siblings and a first degree cousin also had isolated glucocorticoid deficiency. One of the above two siblings died due to renal failure secondary to focal segmental glomerulosclerosis. Conclusion Patients with familial glucocorticoid deficiency should be carefully followed for development of features of nephrotic syndrome.

  14. Molecular basis for genetic deficiency of the second component of human complement

    International Nuclear Information System (INIS)

    Cole, F.S.; Whitehead, A.S.; Auerbach, H.S.; Lint, T.; Zeitz, H.J.; Kilbridge, P.; Colten, H.R.

    1985-01-01

    Genetic deficiency of the second component of complement (C2) is the most common complement-deficiency state among Western Europeans and is frequently associated with autoimmune diseases. To examine the molecular basis of this deficiency, the authors established cultures of blood monocytes from four families with C2-deficient members. Using a hemolytic-plaque assay, [ 35 S]methionine metabolic labeling of proteins in tissue culture and immunoprecipitation, RNA extraction and Northern blot analysis, and DNA restriction-enzyme digestion and Southern blot analysis, the authors found that C2 deficiency is not due to a major gene deletion or rearrangement but is the result of a specific and selective pretranslational regulatory defect in C2 gene expression. This leads to a lack of detectable C2 mRNA and a lack of synthesis of C2 protein. The approach used in this study should prove useful in examination of other plasma protein deficiencies, especially those in which the deficient gene is normally expressed in peripheral-blood monocytes or tissue macrophages and in which ethical considerations preclude the use of liver or other tissue for study

  15. The frequency of vitamin D deficiency among asthmatic Egyptian ...

    African Journals Online (AJOL)

    EL-HAKIM

    The frequency of vitamin D deficiency among asthmatic Egyptian children. INTRODUCTION. Asthma is defined as a common chronic inflammatory disease of the airways characterized by variable and recurrent symptoms, reversible airflow obstruction, and bronchospasm. Children have smaller airways than adults, which ...

  16. Correction of vitamin D deficiency using sublingually administered vitamin D2 in a Crohn's disease patient with mal-absorption and a new ileostomy.

    Science.gov (United States)

    McCullough, Patrick; Heaney, Robert

    2017-10-01

    Vitamin D deficiency has been shown to be associated with many adverse health problems. Studies have shown that patients with Crohn's disease who have low vitamin D levels have a poorer quality of life than those with more adequate levels. It has also been shown that patients with mal-absorption problems have a difficult time achieving normal vitamin D levels in spite of aggressive supplementation, and that exposure to UVB radiation may be the most effective treatment option for these patients. We present a case in which 25-hydroxyvitamin D levels were normalized within 2 weeks in a severely vitamin D deficient patient with Crohn's disease with mal-absorption and a new ileostomy, utilizing sublingually administered vitamin D2. A 58 year-old white female was admitted with a new ileostomy following partial bowel resection due to complications from Crohn's disease. She was found to be severely vitamin D deficient at the time of admission, with a level of 6.1ng/ml on hospital day 3. Her treatment with vitamin D was delayed for a few days. She was initially treated with 5000 units of vitamin D3 orally twice a day for 3days (days 7-10). After discussion with the patient and obtaining her consent, vitamin D3 was stopped, and she was then treated with a total of 8 doses of 50,000 units of vitamin D2 administered sublingually. She was given the first 3 doses on alternating days (days 11, 13, 15), and then 5 more doses on consecutive days (days 17-21). The rise in her 25-hydroxyvitamin D level in response to treatment with sublingual vitamin D2 was significant. On day 10, after receiving 3days of orally administered vitamin D3, her level was 9.8ng/ml. One week later, after receiving 3 sublingual doses of vitamin D2, it rose to 20.3ng/ml. It was then measured on alternating days twice over the next 4days, and it rose to 45.5ng/ml, and then to 47.4ng/ml on the day of discharge to home. The major finding of this study is that sublingual administration of vitamin D2 appears to

  17. Prevalence of vitamin D deficiency in adults presenting for bariatric surgery in Lebanon.

    Science.gov (United States)

    Aridi, Hanaa Dakour; Alami, Ramzi S; Fouani, Tarek; Shamseddine, Ghassan; Tamim, Hani; Safadi, Bassem

    2016-02-01

    Vitamin D deficiency is common among obese patients presenting for bariatric surgery in Europe and North America. The prevalence of vitamin D deficiency in this patient population in Lebanon and the Middle East has not been studied. The aim of this study was to determine the rate of vitamin D deficiency in a cohort of patients presenting for bariatric surgery in Lebanon. American University of Beirut Medical Center, Beirut, Lebanon. Data was extracted from a prospective database of patients presenting for bariatric surgery at the American University of Beirut Medical Center from July 2011 until June 2014. The prevalence of vitamin D deficiency was determined using established cut-offs followed by analysis of the relationship between low vitamin D and certain patient characteristics. More than two thirds of all patients (68.9%) were vitamin D deficient (≤19.9 ng/mL), whereas 22.6% had insufficient levels (20-29.9 ng/mL) and only 8.6 % had sufficient levels (≥30 ng/mL). Vitamin D levels were inversely associated with BMI>50 kg/m(2). Low vitamin D levels were also correlated with younger age, male gender, lack of physical exercise, and nonsunny season. No association was shown between 25-hydroxyvitamin D deficiency and type 2 diabetes mellitus, cardiovascular disease, osteoarticular disease, hypertension, or depression. Vitamin D deficiency is prevalent among patients with Class II or Class III obesity presenting for bariatric surgery in Lebanon. These findings emphasize the need for careful attention when evaluating patients before bariatric surgery and the importance of providing patients with adequate supplementation. Copyright © 2016 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.

  18. Disease: H00146 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available H00146 Alpha-N-acetylgalactosaminidase deficiency, including: Schindler disease; K...ided into three types. Type 1 is Schindler disease, characterized by mental retardation, spasticity ,and myo...n alpha-N-acetylgalactosaminidase deficiency (Schindler/Kanzaki disease). ... JOURNAL ... J Hum Genet 49:1-8 (20... ... TITLE ... The 1.9 a structure of human alpha-N-acetylgalactosaminidase: The molecular basis of Schindler a...eland AM, de Jong JG, Wevers RA, Renier WO, Schindler D, Coll MJ, Chabas A, Sakuraba H, Suzuki Y, van Diggel

  19. Iron-Deficiency Anemia

    Medline Plus

    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. 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 ...

  1. THE PREVALENCE OF VITAMIN D DEFICIENCY AMONG FEMALES STUDENT AT QATAR UNIVERSITY

    OpenAIRE

    Sharif, E.A.; Rizk, N.

    2011-01-01

    Background. Vitamin D deficiency is a major worldwide problem with several health consequence such osteoporosis, hyperten- sion, diabetes mellitus, autoimmune diseases and some cancers. The Prevalence of Vitamin D deficiency among female adult students with associated biochemical markers was not measured in the state of Qatar previously. Aim. Measurement of vitamin D level and other clinical parameters related to vitamin D levels. Methods. Randomly selected 71 female students ...

  2. Partial biotinidase deficiency associated with Coffin-Siris syndrome.

    Science.gov (United States)

    Burlina, A B; Sherwood, W G; Zacchello, F

    1990-06-01

    Coffin-Siris syndrome is an infrequent condition characterised by mental retardation, nail hypoplasia or absence with fifth digit involvement and feeding problems. In addition, sparse scalp hair and chronic intractable eczema has been described in this syndrome. We report a 26-month-old girl with the disease and partial biotinidase deficiency.

  3. MiR-150 deficiency ameliorated hepatosteatosis and insulin resistance in nonalcoholic fatty liver disease via targeting CASP8 and FADD-like apoptosis regulator.

    Science.gov (United States)

    Zhuge, Baozhong; Li, Guohong

    2017-12-16

    The prevalence of Non-alcoholic fatty liver diseases (NAFLD) increased rapidly in the world. However, the pathogenesis of is still unclear. Hepatic steatosis and insulin resistance are considered to be central to the pathophysiology of NAFLD. MicroRNAs are short non-coding RNAs and has been reported to be involved in pathogenesis of NAFLD and related metabolic diseases. Here, we investigated the mechanisms by which miR-150 regulate hepatic steatosis and insulin resistance in high fat diet (HFD) induced NAFLD model. The expression of miR-150 was up-regulated dramatically in both human NAFLD patients and HFD mice model, as well as in hepatocytes treated with oleic acid. miR-150 deficiency ameliorated the hepatic steatosis and insulin resistance significantly in NAFLD mice. miR-150 deficiency decreased the expression of genes related to fatty acid uptake, synthesis and gluconeogenesis, while increased the expression of genes related to fatty acid β-oxidation. Further, we identified that CFLAR is a direct downstream target of miR-150. Overexpression of miR-150 reduced both the mRNA and protein levels of CFLAR in vitro. And overexpression of miR-150 significantly inhibited the luciferase activity of CFLAR 3'-UTR, while the effect of miR-150 was blocked when the binding site of miR-150 within the CFLAR 3'-UTR was mutated. We also found that miR-150 deficiency decreased the expression of p-Jnk1 and p-Ask1, while the effect of miR-150 on steatosis and insulin signaling was blocked by CFLAR overexpression. In conclusion, our data indicated that miR-150 potentially contributes to the hepatic steatosis and insulin resistance in NAFLD. miR-150/CFLAR pathway may be a new therapeutic strategy against NAFLD. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Inherited coagulation factor VII and X deficiencies associated with severe bleeding diathesis: Molecular genetics and pathophysiology

    NARCIS (Netherlands)

    Borensztajn, K.; Spek, C. A.

    2005-01-01

    The rare inherited coagulation disorders are a fascinating group of diseases that have provided us with important insights into the structure and functions of their respective deficient proteins. Factor (F)VII deficiency is the commonest of these inherited disorders of coagulation, whereas FX

  5. Deficiency of 25-Hydroxyvitamin D and Dyslipidemia in Indian Subjects

    Directory of Open Access Journals (Sweden)

    Jaydip Ray Chaudhuri

    2013-01-01

    Full Text Available Background. Vitamin D deficiency is widespread throughout the world. Several reports have incriminated vitamin D deficiency as the cause of rickets, osteomalacia, and other chronic diseases. Recent studies have suggested a possible link between deficiency of 25-hydroxyvitamin D and dyslipidemia. Aim. To investigate the association between 25-hydroxyvitamin D deficiency and dyslipidemia in Indian subjects. Methodology. We recruited 150 asymptomatic consecutive subjects from patients’ attendees at the Departments of Neurology and Medicine in Yashoda Hospital, Hyderabad, India. Study period was from October 2011 to March 2012. All subjects underwent 25-hydroxyvitamin D assay by chemiluminescent microparticle immunoassay, fasting blood sugar and lipid profile, calcium, phosphorus, alkaline phosphatase, and C-reactive protein (CRP. Results. Out of 150 subjects, men were 82 (54.6%, and mean age was 49.4 (±15.6 years. Among risk factors, hypertension was noted in 63/150 (42%, 25-hydroxyvitamin D deficiency in 59/150 (39.3%, diabetes in 45/150 (30%, dyslipidemia in 60 (40%, smoking in 35/150 (23.3%, and alcoholism in 27/150 (18%. Deficiency of 25-hydroxyvitamin D was significantly associated with dyslipidemia (P=0.0001, mean serum glucose (P=0.0002 mean CRP (P=0.04, and mean alkaline phosphatase (P=0.01. Multivariate analysis showed that 25-hydroxyvitamin D deficiency was independently associated with dyslipidemia (odds ratio: 1.9; 95% CI : 1.1–3.5. Conclusions. We found that deficiency of 25-hydroxyvitamin D was independently associated with dyslipidemia in Indian subjects.

  6. Cobalamin deficiency, hyperhomocysteinemia, and dementia

    Directory of Open Access Journals (Sweden)

    Steven F Werder

    2010-04-01

    : 200 picograms per milliliter or less is low, and 201 to 350 picograms per milliliter is borderline low. Other tests may be indicated, including plasma homocysteine, serum methylmalonic acid, antiparietal cell and anti-intrinsic factor antibodies, and serum gastrin level. In B12 deficiency dementia with versus without pernicious anemia, there appear to be different manifestations, need for further workup, and responses to treatment. Dementia of the Alzheimer’s type is a compatible diagnosis when B12 deficiency is found, unless it is caused by pernicious anemia. Patients with pernicious anemia generally respond favorably to supplemental B12 treatment, especially if pernicious anemia is diagnosed early in the course of the disease. Some patients without pernicious anemia, but with B12 deficiency and either mild cognitive impairment or mild to moderate dementia, might show some degree of cognitive improvement with supplemental B12 treatment. Evidence that supplemental B12 treatment is beneficial for patients without pernicious anemia, but with B12 deficiency and moderately-severe to severe dementia is scarce. Oral cyanocobalamin is generally favored over intramuscular cyanocobalamin.Keywords: Alzheimer, dementia, cognitive impairment, cognitive dysfunction, cobalamin, cyanocobalamin, B12, homocysteine, hyperhomocysteinemia, homocystinuria

  7. Iron-Deficiency Anemia

    Medline Plus

    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 ...

  8. Neurodegeneration in D-bifunctional protein deficiency: diagnostic clues and natural history using serial magnetic resonance imaging

    Energy Technology Data Exchange (ETDEWEB)

    Khan, Aneal [University of Calgary, Department of Medical Genetics and Pediatrics, Alberta Children' s Hospital, Calgary, AB (Canada); Wei, Xing-Chang [University of Calgary, Department of Radiology, Alberta Children' s Hospital, Calgary, AB (Canada); Snyder, Floyd F. [Alberta Children' s Hospital, Biochemical Genetics Laboratory, Calgary, AB (Canada); Mah, Jean K. [University of Calgary, Division of Neurology, Department of Pediatrics, Calgary, AB (Canada); Waterham, Hans; Wanders, Ronald J.A. [University of Amsterdam, Academic Medical Center, Lab Genetic Metabolic Diseases, Amsterdam (Netherlands)

    2010-12-15

    We report serial neurodegenerative changes on neuroimaging in a rare peroxisomal disease called D-bifunctional protein deficiency. The pattern of posterior to anterior demyelination with white matter disease resembles X-linked adrenoleukodystrophy. We feel this case is important to (1) highlight that D-bifunctional protein deficiency should be considered in cases where the neuroimaging resembles X-linked adrenoleukodystrophy, (2) to show different stages of progression to help identify this disease using neuroimaging in children, and (3) to show that neuroimaging suggesting a leukodystrophy can warrant peroxisomal beta-oxidation studies in skin fibroblasts even when plasma very long chain fatty acids are normal. (orig.)

  9. Effects of early vitamin D deficiency rickets on bone and dental health, growth and immunity.

    Science.gov (United States)

    Zerofsky, Melissa; Ryder, Mark; Bhatia, Suruchi; Stephensen, Charles B; King, Janet; Fung, Ellen B

    2016-10-01

    Vitamin D deficiency is associated with adverse health outcomes, including impaired bone growth, gingival inflammation and increased risk for autoimmune disease, but the relationship between vitamin D deficiency rickets in childhood and long-term health has not been studied. In this study, we assessed the effect of early vitamin D deficiency on growth, bone density, dental health and immune function in later childhood to determine if children previously diagnosed with rickets were at greater risk of adverse health outcomes compared with healthy children. We measured serum 25-hydroxyvitamin D, calcium, parathyroid hormone, bone mineral density, anthropometric measures, dietary habits, dental health, general health history, and markers of inflammation in 14 previously diagnosed rickets case children at Children's Hospital Oakland Research Center. We compared the findings in the rickets cases with 11 healthy children selected from the population of CHO staff families. Fourteen mothers of the rickets cases, five siblings of the rickets cases, and seven mothers of healthy children also participated. Children diagnosed with vitamin D deficiency rickets had a greater risk of fracture, greater prevalence of asthma, and more dental enamel defects compared with healthy children. Given the widespread actions of vitamin D, it is likely that early-life vitamin D deficiency may increase the risk of disease later in childhood. Further assessment of the long-term health effects of early deficiency is necessary to make appropriate dietary recommendations for infants at risk of deficiency. © 2015 John Wiley & Sons Ltd.

  10. 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,...

  11. Familial LCAT deficiency: from renal replacement to enzyme replacement

    NARCIS (Netherlands)

    Stoekenbroek, R. M.; van den Bergh Weerman, M. A.; Hovingh, G. K.; Potter van Loon, B. J.; Siegert, C. E. H.; Holleboom, A. G.

    2013-01-01

    Familial LCAT deficiency (FLD) is a recessive lipid disorder ultimately leading to end-stage renal disease (ESRD). We present two brothers with considerable variation in the age at which they developed ESRD. Kidney biopsies revealed both tubular and glomerular pathology. To date, no causal therapy

  12. Loss of synaptic zinc transport in progranulin deficient mice may contribute to progranulin-associated psychopathology and chronic pain.

    Science.gov (United States)

    Hardt, Stefanie; Heidler, Juliana; Albuquerque, Boris; Valek, Lucie; Altmann, Christine; Wilken-Schmitz, Annett; Schäfer, Michael K E; Wittig, Ilka; Tegeder, Irmgard

    2017-11-01

    Affective and cognitive processing of nociception contributes to the development of chronic pain and vice versa, pain may precipitate psychopathologic symptoms. We hypothesized a higher risk for the latter with immanent neurologic diseases and studied this potential interrelationship in progranulin-deficient mice, which are a model for frontotemporal dementia, a disease dominated by behavioral abnormalities in humans. Young naïve progranulin deficient mice behaved normal in tests of short-term memory, anxiety, depression and nociception, but after peripheral nerve injury, they showed attention-deficit and depression-like behavior, over-activity, loss of shelter-seeking, reduced impulse control and compulsive feeding behavior, which did not occur in equally injured controls. Hence, only the interaction of 'pain x progranulin deficiency' resulted in the complex phenotype at young age, but neither pain nor progranulin deficiency alone. A deep proteome analysis of the prefrontal cortex and olfactory bulb revealed progranulin-dependent alterations of proteins involved in synaptic transport, including neurotransmitter transporters of the solute carrier superfamily. In particular, progranulin deficiency was associated with a deficiency of nuclear and synaptic zinc transporters (ZnT9/Slc30a9; ZnT3/Slc30a3) with low plasma zinc. Dietary zinc supplementation partly normalized the attention deficit of progranulin-deficient mice, which was in part reminiscent of autism-like and compulsive behavior of synaptic zinc transporter Znt3-knockout mice. Hence, the molecular studies point to defective zinc transport possibly contributing to progranulin-deficiency-associated psychopathology. Translated to humans, our data suggest that neuropathic pain may precipitate cognitive and psychopathological symptoms of an inherent, still silent neurodegenerative disease. Copyright © 2017. Published by Elsevier B.V.

  13. 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 ...

  14. Iron-Deficiency Anemia

    Medline Plus

    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 ...

  15. Chronic Latent Magnesium Deficiency in Obesity Decreases Positive Effects of Vitamin D on Cardiometabolic Risk Indicators.

    Science.gov (United States)

    Stokic, Edita; Romani, Andrea; Ilincic, Branislava; Kupusinac, Aleksandar; Stosic, Zoran; Isenovic, Esma R

    2017-08-21

    Obesity and micronutrient deficiencies contribute to the risk of cardiometabolic diseases such are type 2 diabetes mellitus and cardiovascular disease (CVD). We examined the frequency of concomitant deficit of magnesium (Mg) and vitamin D in obese patients and evaluated the connection of these combined deficiencies with indicators of cardiometabolic risk in non-diabetic subjects. Non-diabetic middle aged adults (n = 80; mean age 36 ± 4 years, 52% women) were recruited based on weight/adiposity parameters [i.e. body mass index (BMI) and body fat percentage (FAT%)]. Cardiometabolic risk indicators [insulin resistance (Homeostatic Model Assessment for insulin resistance (HOMA-IR)) and CVD risk (Framingham risk score for predicting 10-year CVD)], Mg status [i.e. total serum Mg concentration (TMg), chronic latent Mg deficiency (CLMD) - 0.75-0.85 mmol/L], vitamin D status [i.e. serum concentration of 25-hydroxyvitamin D (25(OH)D), vitamin D deficiency <50 nmol/l] were assessed. Among obese subjects 36% presented a combination of vitamin D deficiency and CLMD. In all studied patients, 25(OH)D and TMg levels both, individually and combined, showed a negative linear correlation with HOMA-IR and CVD risk. In subjects with CLMD (TMg ˂0.85 mmol/L), a negative linear coefficient was found between 25(OH)D and, HOMA-IR and CVD risk, compared with subjects with normal TMg status (TMg ≥0.85 mmol/L). CLMD and vitamin D deficiency may commonly be present in obese non-diabetic subjects. Individually and combined, both deficiencies predispose non-diabetic patients to increased risk of cardiometabolic diseases. Maintaining normal Mg status may improve the beneficial effects of vitamin D on cardiometabolic risk indicators. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  16. Monoamine oxidase deficiency in males with an X chromosome deletion.

    Science.gov (United States)

    Sims, K B; de la Chapelle, A; Norio, R; Sankila, E M; Hsu, Y P; Rinehart, W B; Corey, T J; Ozelius, L; Powell, J F; Bruns, G

    1989-01-01

    Mapping of the human MAOA gene to chromosomal region Xp21-p11 prompted our study of two affected males in a family previously reported to have Norrie disease resulting from a submicroscopic deletion in this chromosomal region. In this investigation we demonstrate in these cousins deletion of the MAOA gene, undetectable levels of MAO-A and MAO-B activities in their fibroblasts and platelets, respectively, loss of mRNA for MAO-A in fibroblasts, and substantial alterations in urinary catecholamine metabolites. The present study documents that a marked deficiency of MAO activity is compatible with life and that genes for MAO-A and MAO-B are near each other in this Xp chromosomal region. Some of the clinical features of these MAO deletion patients may help to identify X-linked MAO deficiency diseases in humans.

  17. Selenium deficiency aggravates T-2 toxin-induced injury of primary neonatal rat cardiomyocytes through ER stress.

    Science.gov (United States)

    Xu, Jing; Pan, Shengchi; Gan, Fang; Hao, Shu; Liu, Dandan; Xu, Haibin; Huang, Kehe

    2018-04-01

    Keshan disease is a potentially fatal cardiomyopathy in humans. Selenium deficiency, T-2 toxin, and myocarditis virus are thought to be the major factors contributing to Keshan disease. But the relationship among these three factors is poorly described. This study aims to explore whether selenium deficiency aggravates T-2 toxin-induced cardiomyocyte injury and its underlying mechanism. Cardiomyocytes were isolated from neonatal rat and cultured at the physiological (2.0 μM) or lower concentrations of selenium with different concentrations of T-2 toxin. Our results showed that selenium deficiencies aggravated T-2 toxin-induced cardiomyocyte injury in a concentration-dependent manner as demonstrated by MTT bioassay, LDH activity, reactive oxygen species levels and caspase 3 protein expressions. T-2 toxin treatment significantly increased mRNA expressions for stress proteins GRP78 and CHOP in cardiomyocytes compared with the control. Selenium deficiencies further promoted GRP78, CHOP and p-eIF2α expressions. Knockdown of CHOP by the specific small interfering RNA eliminated the effect of selenium deficiencies on T-2 toxin-induced injury. It could be concluded that selenium deficiency aggravates T-2 toxin-induced cardiomyocyte injury through initiating more aggressive endoplasmic reticulum stress. Copyright © 2018 Elsevier B.V. All rights reserved.

  18. Cellular Signaling and Production of Galactose-Deficient IgA1 in IgA Nephropathy, an Autoimmune Disease

    Directory of Open Access Journals (Sweden)

    Colin Reily

    2014-01-01

    Full Text Available Immunoglobulin A (IgA nephropathy (IgAN, the leading cause of primary glomerulonephritis, is characterized by IgA1-containing immunodeposits in the glomeruli. IgAN is a chronic disease, with up to 40% of patients progressing to end-stage renal disease, with no disease-specific treatment. Multiple studies of the origin of the glomerular immunodeposits have linked elevated circulating levels of aberrantly glycosylated IgA1 (galactose-deficient in some O-glycans; Gd-IgA1 with formation of nephritogenic Gd-IgA1-containing immune complexes. Gd-IgA1 is recognized as an autoantigen in susceptible individuals by anti-glycan autoantibodies, resulting in immune complexes that may ultimately deposit in the kidney and induce glomerular injury. Genetic studies have revealed that an elevated level of Gd-IgA1 in the circulation of IgAN patients is a hereditable trait. Moreover, recent genome-wide association studies have identified several immunity-related loci that associated with IgAN. Production of Gd-IgA1 by IgA1-secreting cells of IgAN patients has been attributed to abnormal expression and activity of several key glycosyltransferases. Substantial evidence is emerging that abnormal signaling in IgA1-producing cells is related to the production of Gd-IgA1. As Gd-IgA1 is the key autoantigen in IgAN, understanding the genetic, biochemical, and environmental aspects of the abnormal signaling in IgA1-producing cells will provide insight into possible targets for future disease-specific therapy.

  19. Creatine Deficiency Syndrome could be Missed Easily: A Case Report of Guanidinoacetate Methyltransferase Deficiency Presented with Neurodevelopmental Delay, Seizures, and Behavioral Changes, but Normal Structural MRI.

    Science.gov (United States)

    Pacheva, Iliyana; Ivanov, Ivan; Penkov, Marin; Kancheva, Daliya; Jordanova, Albena; Ivanova, Mariya

    2016-09-01

    A case with GAMT deficiency (homozygous c.64dupG mutation) presented with neurodevelopmental delay, rare seizures, behavioral disturbances, and mild hypotonia, posing diagnostic challenges. Metabolic investigations showed low creatinine in plasma and urine (guanidinoacetate couldn't be investigated) and slightly elevated lactate. MRI was normal. Correct diagnosis was possible only after MR spectroscopy was performed at age 5½ years. A homozygous c.64dupG mutation of the GAMT gene was identified in the proband. In conclusion, every case with neurodevelopmental delay or arrest, especially when accompanied by seizures, behavioral impairment, muscle hypotonia or extrapyramidal symptoms should undergo MRI with MR spectroscopy. Normal structural MRI doesn't exclude a creatine deficiency syndrome. Biochemical investigations of guanidinoacetate, creatine, and creatinine in body fluid should be done to diagnose cerebral creatine deficiency syndromes and to specify the deficient enzyme. Thus, a treatable disease will not be missed. © 2016 by the Association of Clinical Scientists, Inc.

  20. Metabolic disorders and nutritional status in autoimmune thyroid diseases

    Directory of Open Access Journals (Sweden)

    Anna Kawicka

    2015-01-01

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

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

    Science.gov (United States)

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

    2015-01-02

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

  2. Treatment of autoinflammatory diseases

    DEFF Research Database (Denmark)

    Ter Haar, Nienke; Lachmann, Helen; Özen, Seza

    2013-01-01

    OBJECTIVE: To evaluate the response to treatment of autoinflammatory diseases from an international registry and an up-to-date literature review. METHODS: The response to treatment was studied in a web-based registry in which clinical information on anonymised patients with autoinflammatory...... diseases was collected retrospectively as part of the Eurofever initiative. Participating hospitals included paediatric rheumatology centres of the Paediatric Rheumatology International Trial Organisation network and adult centres with a specific interest in autoinflammatory diseases. The following...... diseases were included: familial Mediterranean fever (FMF), cryopyrin-associated periodic syndromes (CAPS), tumour necrosis factor (TNF)-receptor associated periodic syndrome (TRAPS), mevalonate kinase deficiency (MKD), pyogenic arthritis pustulosis acne (PAPA) syndrome, deficiency of interleukin-1...

  3. Severe deficiency of 25-hydroxyvitamin D3 (25-OH-D3) is associated with high disease activity of rheumatoid arthritis

    DEFF Research Database (Denmark)

    Haga, Hans-Jacob; Schmedes, Anne; Naderi, Yusuf

    2013-01-01

    This study aims to measure the serum level of 25-hydroxyvitamin D₃ (25-OH-D₃) in 302 patients with rheumatoid arthritis (RA), studying the association to disease activity. Three hundred two RA patients underwent clinical examination and serological analysis. 25-Hydroxyvitamin D₃ was determined...... by high-performance liquid chromatography-tandem mass spectrometry. Vitamin D₃ deficiency defined as serum levels of 25-hydroxyvitamin D₃ below 50 nmol/l was detected in 101 RA patients (33.4 %). There was no significant correlation between the serum level of 25-hydroxyvitamin D₃ and Disease Activity...... Score 28 (DAS28) (3w) score. In a subpopulation of RA patients with very low serum level of 25-OH-D₃ (≤15 nmol/l) (n = 15), there were significant differences compared to patients with normal 25-OH-D3 (n = 200): higher percentage of patients with positive rheumatoid factor (100.0 versus 77.5 %; p = 0...

  4. Apoptosis and signalling in acid sphingomyelinase deficient cells

    Directory of Open Access Journals (Sweden)

    Sillence Dan J

    2001-11-01

    Full Text Available Abstract Background Recent evidence suggests that the activation of a non-specific lipid scramblase during apoptosis induces the flipping of sphingomyelin from the cell surface to the cytoplasmic leaftet of the plasma membrane. Inner leaflet sphingomyelin is then cleaved to ceramide by a neutral sphingomyelinase. The production of this non-membrane forming lipid induces blebbing of the plasma membrane to aid rapid engulfment by professional phagocytes. However contrary evidence suggests that cells which are deficient in acid sphingomyelinase are defective in apoptosis signalling. This data has been interpreted as support for the activation of acid sphingomyelinase as an early signal in apoptosis. Hypothesis An alternative explanation is put forward whereby the accumulation of intracellular sphingomyelin in sphingomyelinase deficient cells leads to the formation of intracellular rafts which lead to the sequestration of important signalling molecules that are normally present on the cell surface where they perform their function. Testing the hypothesis It is expected that the subcellular distribution of important signalling molecules is altered in acid sphingomyelinase deficient cells, leading to their sequestration in late endosomes / lysosomes. Other sphingolipid storage diseases such as Niemann-Pick type C which have normal acid sphingomyelinase activity would also be expected to show the same phenotype. Implications of the hypothesis If true the hypothesis would provide a mechanism for the pathology of the sphingolipid storage diseases at the cellular level and also have implications for the role of ceramide in apoptosis.

  5. Optimal management of iron deficiency anemia due to poor dietary intake

    Directory of Open Access Journals (Sweden)

    García-López S

    2011-10-01

    Full Text Available Kattalin Aspuru1, Carlos Villa2, Fernando Bermejo2, Pilar Herrero3, Santiago García López1 1Digestive Department, Hospital Universitario Miguel Servet (Miguel Servet University Hospital, Zaragoza, 2Digestive Department, Hospital Universitario de Fuenlabrada (Fuenlabrada University Hospital, Madrid, 3Professional College of Nutritionists and Dietitians of Aragon, Zaragoza, Spain Abstract: Iron is necessary for the normal development of multiple vital processes. Iron deficiency (ID may be caused by several diseases, even by physiological situations that increase requirements for this mineral. One of its possible causes is a poor dietary iron intake, which is infrequent in developed countries, but quite common in developing areas. In these countries, dietary ID is highly prevalent and comprises a real public health problem and a challenge for health authorities. ID, with or without anemia, can cause important symptoms that are not only physical, but can also include a decreased intellectual performance. All this, together with a high prevalence, can even have negative implications for a community’s economic and social development. Treatment consists of iron supplements. Prevention of ID obviously lies in increasing the dietary intake of iron, which can be difficult in developing countries. In these regions, foods with greater iron content are scarce, and attempts are made to compensate this by fortifying staple foods with iron. The effectiveness of this strategy is endorsed by multiple studies. On the other hand, in developed countries, ID with or without anemia is nearly always associated with diseases that trigger a negative balance between iron absorption and loss. Its management will be based on the treatment of underlying diseases, as well as on oral iron supplements, although these latter are limited by their tolerance and low potency, which on occasions may compel a change to intravenous administration. Iron deficiency has a series of

  6. 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.).

  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. IRF4 Deficiency Abrogates Lupus Nephritis Despite Enhancing Systemic Cytokine Production

    Science.gov (United States)

    Lech, Maciej; Weidenbusch, Marc; Kulkarni, Onkar P.; Ryu, Mi; Darisipudi, Murthy Narayana; Susanti, Heni Eka; Mittruecker, Hans-Willi; Mak, Tak W.

    2011-01-01

    The IFN-regulatory factors IRF1, IRF3, IRF5, and IRF7 modulate processes involved in the pathogenesis of systemic lupus and lupus nephritis, but the contribution of IRF4, which has multiple roles in innate and adaptive immunity, is unknown. To determine a putative pathogenic role of IRF4 in lupus, we crossed Irf4-deficient mice with autoimmune C57BL/6-(Fas)lpr mice. IRF4 deficiency associated with increased activation of antigen-presenting cells in C57BL/6-(Fas)lpr mice, resulting in a massive increase in plasma levels of TNF and IL-12p40, suggesting that IRF4 suppresses cytokine release in these mice. Nevertheless, IRF4 deficiency completely protected these mice from glomerulonephritis and lung disease. The mice were hypogammaglobulinemic and lacked antinuclear and anti-dsDNA autoantibodies, revealing the requirement of IRF4 for the maturation of plasma cells. As a consequence, Irf4-deficient C57BL/6-(Fas)lpr mice neither developed immune complex disease nor glomerular activation of complement. In addition, lack of IRF4 impaired the maturation of Th17 effector T cells and reduced plasma levels of IL-17 and IL-21, which are cytokines known to contribute to autoimmune tissue injury. In summary, IRF4 deficiency enhances systemic inflammation and the activation of antigen-presenting cells but also prevents the maturation of plasma cells and effector T cells. Because these adaptive immune effectors are essential for the evolution of lupus nephritis, we conclude that IRF4 promotes the development of lupus nephritis despite suppressing antigen-presenting cells. PMID:21742731

  9. Association of GATA2 Deficiency With Severe Primary Epstein-Barr Virus (EBV) Infection and EBV-associated Cancers.

    Science.gov (United States)

    Cohen, Jeffrey I; Dropulic, Lesia; Hsu, Amy P; Zerbe, Christa S; Krogmann, Tammy; Dowdell, Kennichi; Hornung, Ronald L; Lovell, Jana; Hardy, Nancy; Hickstein, Dennis; Cowen, Edward W; Calvo, Katherine R; Pittaluga, Stefania; Holland, Steven M

    2016-07-01

    Most patients infected with Epstein-Barr virus (EBV) are asymptomatic, have nonspecific symptoms, or have self-limiting infectious mononucleosis. EBV, however, may result in severe primary disease or cancer. We report EBV diseases associated with GATA2 deficiency at one institution and describe the hematology, virology, and cytokine findings. Seven patients with GATA2 deficiency developed severe EBV disease. Three presented with EBV infectious mononucleosis requiring hospitalization, 1 had chronic active EBV disease (B-cell type), 1 had EBV-associated hydroa vacciniforme-like lymphoma with hemophagocytic lymphohistiocytosis, and 2 had EBV-positive smooth muscle tumors. Four of the 7 patients had severe warts and 3 had disseminated nontuberculous mycobacterial infections. All of the patients had low numbers of monocytes, B cells, CD4 T cells, and natural killer cells. All had elevated levels of EBV in the blood; 2 of 3 patients tested had expression of the EBV major immediate-early gene in the blood indicative of active EBV lytic infection. Mean plasma levels of tumor necrosis factor α, interferon γ, and interferon gamma-induced protein 10 were higher in patients with GATA2 deficiency than in controls. GATA2 is the first gene associated with EBV hydroa vacciniforme-like lymphoma. GATA2 deficiency should be considered in patients with severe primary EBV infection or EBV-associated cancer, especially in those with disseminated nontuberculous mycobacterial disease and warts. Published by Oxford University Press for the Infectious Diseases Society of America 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  10. Simultaneous occurrence of hereditary C6 and C2 deficiency in a French-Canadian family.

    Science.gov (United States)

    Delâge, J M; Lehner-Netsch, G; Lafleur, R; Simard, J; Brun, G; Prochazka, E

    1979-06-01

    The sera of four sisters were found to lack the sixth component of complement (C6) and the serum of one was also partially deficient in the second component (C2). Two other blood relatives were found to be heterozygous for both deficiencies, while only one sibling had normal values. The father of these eight siblings was heterozygous for C2D and C6D and in the third generation, six children were heterozygous for C6 deficiency was treated for chronic active brucel-transmitted; the C6 deficiency was not linked to the HLA system, while the C2-deficiency segregated with the haplotype A10,B18. The proband, homozygous for C6 deficiency was treated for chronic active Brucellosis and in another sibling with C6 deficiency, toxoplasmosis was diagnosed. Neither bleeding disorders nor a tendency to collagen diseases have been observed and the opsonic activity was normal in the sera of all family members.

  11. A novel SERPINA1 mutation causing serum alpha(1-antitrypsin deficiency.

    Directory of Open Access Journals (Sweden)

    Darren N Saunders

    Full Text Available Mutations in the SERPINA1 gene can cause deficiency in the circulating serine protease inhibitor α(1-Antitrypsin (α(1AT. α(1AT deficiency is the major contributor to pulmonary emphysema and liver disease in persons of European ancestry, with a prevalence of 1 in 2500 in the USA. We present the discovery and characterization of a novel SERPINA1 mutant from an asymptomatic Middle Eastern male with circulating α(1AT deficiency. This 49 base pair deletion mutation (T379Δ, originally mistyped by IEF, causes a frame-shift replacement of the last sixteen α(1AT residues and adds an extra twenty-four residues. Functional analysis showed that the mutant protein is not secreted and prone to intracellular aggregation.

  12. Omega-3 deficiency impairs honey bee learning

    Science.gov (United States)

    Arien, Yael; Dag, Arnon; Zarchin, Shlomi; Masci, Tania

    2015-01-01

    Deficiency in essential omega-3 polyunsaturated fatty acids (PUFAs), particularly the long-chain form of docosahexaenoic acid (DHA), has been linked to health problems in mammals, including many mental disorders and reduced cognitive performance. Insects have very low long-chain PUFA concentrations, and the effect of omega-3 deficiency on cognition in insects has not been studied. We show a low omega-6:3 ratio of pollen collected by honey bee colonies in heterogenous landscapes and in many hand-collected pollens that we analyzed. We identified Eucalyptus as an important bee-forage plant particularly poor in omega-3 and high in the omega-6:3 ratio. We tested the effect of dietary omega-3 deficiency on olfactory and tactile associative learning of the economically highly valued honey bee. Bees fed either of two omega-3–poor diets, or Eucalyptus pollen, showed greatly reduced learning abilities in conditioned proboscis-extension assays compared with those fed omega-3–rich diets, or omega-3–rich pollen mixture. The effect on performance was not due to reduced sucrose sensitivity. Omega-3 deficiency also led to smaller hypopharyngeal glands. Bee brains contained high omega-3 concentrations, which were only slightly affected by diet, suggesting additional peripheral effects on learning. The shift from a low to high omega-6:3 ratio in the Western human diet is deemed a primary cause of many diseases and reduced mental health. A similar shift seems to be occurring in bee forage, possibly an important factor in colony declines. Our study shows the detrimental effect on cognitive performance of omega-3 deficiency in a nonmammal. PMID:26644556

  13. Alpha1-antitrypsin deficiency: a clinical-genetic overview

    Directory of Open Access Journals (Sweden)

    Abboud RT

    2011-03-01

    Full Text Available Raja T Abboud1, Tanya N Nelson2, Benjamin Jung2, Andre Mattman31Department of Medicine, Respiratory Division, University of British Columbia, Vancouver, BC, Canada; 2Department of Pathology and Laboratory Medicine, Children's and Women's Health Centre of British Columbia, University of British Columbia, Vancouver, BC, Canada; 3Department of Pathology and Laboratory Medicine, St. Paul's Hospital, University of British Columbia, Vancouver, BC, CanadaAbstract: Severe α1-antitrypsin deficiency (AATD is an inherited disorder, leading to development of emphysema in smokers at a relatively young age with disability in their forties or fifties. The emphysema results from excessive elastin degradation by neutrophil elastase as a result of the severe deficiency of its major inhibitor α1-antitrypsin (AAT. The AAT expression is determined by the SERPINA1 gene which expresses codominant alleles. The three most common alleles are the normal M, the S with plasma levels of 60% of normal, and the severely deficient Z with levels of about 15% of normal. Homozygosity for the Z mutant allele is associated with retention of abnormal AAT in the liver, which may lead to neonatal hepatitis, liver disease in children, and liver disease in adults. Regular intravenous infusions of purified human AAT (AAT augmentation therapy have been used to partially correct the biochemical defect and protect the lung against further injury. Two randomized controlled trials showed a trend of slower progression of emphysema by chest computerized tomography. Integrated analysis of these two studies indicated significantly slower progression of emphysema. AAT is quantified by immunologic measurement of AAT in serum, the phenotype characterized by isoelectric focusing, the common genotypes by targeted DNA analysis, and by sequencing the coding region of the gene when the AAT abnormality remains undefined. AATD is often unrecognized, and diagnosis delayed. Testing for AATD is recommended

  14. 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.

  15. Osteomalacia in Crohn's disease.

    Science.gov (United States)

    Dedeoglu, Meryem; Garip, Yesim; Bodur, Hatice

    2014-01-01

    Osteomalacia is a metabolic bone disorder characterized by impaired mineralization of the bone matrix. Vitamin D deficiency due to malabsorption syndromes may cause osteomalacia. This is a case of a patient with a 6-year history of seronegative spondyloarthropathy associated with Crohn's disease who was admitted to our outpatient clinic with symptoms of osteomalacia. Osteomalacia is a metabolic bone disease characterized by an impaired mineralization of the bone matrix, frequently caused by disorders in vitamin D or phosphate metabolism. Vitamin D deficiency due to malabsorption syndromes (e.g., Crohn's disease, ulcerative colitis, celiac disease, and jejuno-ileal bypass for obesity) may cause osteomalacia. A 43-year-old male presented with fatigue, low back pain, and morning stiffness. He had a 6-year history of seronegative spondyloarthropathy associated with Crohn's disease. Laboratory findings revealed low serum calcium, low 25-hydroxy vitamin D3, normal phosphorus, elevated parathyroid hormone, and alkaline phosphatase levels. Radiographs revealed grade IV sacroiliitis and Looser zones. He was diagnosed with osteomalacia due to the malabsorption of vitamin D. His symptoms and signs were relieved with supplements of vitamin D and calcium. Osteomalacia should be considered in differential diagnosis when assessing low back pain in the patients with chronic inflammatory bowel disease. Vitamin D deficiency should be treated with vitamin D supplementation in patients with Crohn's disease to prevent osteomalacia.

  16. Rethinking Iron Regulation and Assessment in Iron Deficiency, Anemia of Chronic Disease, and Obesity: Introducing Hepcidin

    Science.gov (United States)

    Tussing-Humphreys, Lisa; Pustacioglu, Cenk; Nemeth, Elizabeta; Braunschweig, Carol

    2012-01-01

    Adequate iron availability is essential to human development and overall health. Iron is a key component of oxygen-carrying proteins, has a pivotal role in cellular metabolism, and is essential to cell growth and differentiation. Inadequate dietary iron intake, chronic and acute inflammatory conditions, and obesity are each associated with alterations in iron homeostasis. Tight regulation of iron is necessary because iron is highly toxic and human beings can only excrete small amounts through sweat, skin and enterocyte sloughing, and fecal and menstrual blood loss. Hepcidin, a small peptide hormone produced mainly by the liver, acts as the key regulator of systemic iron homeostasis. Hepcidin controls movement of iron into plasma by regulating the activity of the sole known iron exporter ferroportin-1. Downregulation of the ferroportin-1 exporter results in sequestration of iron within intestinal enterocytes, hepatocytes, and iron-storing macrophages reducing iron bioavailability. Hepcidin expression is increased by higher body iron levels and inflammation and decreased by anemia and hypoxia. Importantly, existing data illustrate that hepcidin may play a significant role in the development of several iron-related disorders, including the anemia of chronic disease and the iron dysregulation observed in obesity. Therefore, the purpose of this article is to discuss iron regulation, with specific emphasis on systemic regulation by hepcidin, and examine the role of hepcidin within several disease states, including iron deficiency, anemia of chronic disease, and obesity. The relationship between obesity and iron depletion and the clinical assessment of iron status will also be reviewed. PMID:22717199

  17. Vitamin B12 deficiency results in severe oxidative stress, leading to memory retention impairment in Caenorhabditis elegans.

    Science.gov (United States)

    Bito, Tomohiro; Misaki, Taihei; Yabuta, Yukinori; Ishikawa, Takahiro; Kawano, Tsuyoshi; Watanabe, Fumio

    2017-04-01

    Oxidative stress is implicated in various human diseases and conditions, such as a neurodegeneration, which is the major symptom of vitamin B 12 deficiency, although the underlying disease mechanisms associated with vitamin B 12 deficiency are poorly understood. Vitamin B 12 deficiency was found to significantly increase cellular H 2 O 2 and NO content in Caenorhabditis elegans and significantly decrease low molecular antioxidant [reduced glutathione (GSH) and L-ascorbic acid] levels and antioxidant enzyme (superoxide dismutase and catalase) activities, indicating that vitamin B 12 deficiency induces severe oxidative stress leading to oxidative damage of various cellular components in worms. An NaCl chemotaxis associative learning assay indicated that vitamin B 12 deficiency did not affect learning ability but impaired memory retention ability, which decreased to approximately 58% of the control value. When worms were treated with 1mmol/L GSH, L-ascorbic acid, or vitamin E for three generations during vitamin B 12 deficiency, cellular malondialdehyde content as an index of oxidative stress decreased to the control level, but the impairment of memory retention ability was not completely reversed (up to approximately 50%). These results suggest that memory retention impairment formed during vitamin B 12 deficiency is partially attributable to oxidative stress. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  18. Clinical and Molecular Heterogeneity of RTEL1 Deficiency

    Directory of Open Access Journals (Sweden)

    Marcin W. Wlodarski

    2017-05-01

    Full Text Available Typical features of dyskeratosis congenita (DC resulting from excessive telomere shortening include bone marrow failure (BMF, mucosal fragility, and pulmonary or liver fibrosis. In more severe cases, immune deficiency and recurring infections can add to disease severity. RTEL1 deficiency has recently been described as a major genetic etiology, but the molecular basis and clinical consequences of RTEL1-associated DC are incompletely characterized. We report our observations in a cohort of six patients: five with novel biallelic RTEL1 mutations p.Trp456Cys, p.Ile425Thr, p.Cys1244ProfsX17, p.Pro884_Gln885ins53X13, and one with novel heterozygous mutation p.Val796AlafsX4. The most unifying features were hypocellular BMF in 6/6 and B-/NK-cell lymphopenia in 5/6 patients. In addition, three patients with homozygous mutations p.Trp456Cys or p.Ile425Thr also suffered from immunodeficiency, cerebellar hypoplasia, and enteropathy, consistent with Hoyeraal-Hreidarsson syndrome. Chromosomal breakage resembling a homologous recombination defect was detected in patient-derived fibroblasts but not in hematopoietic compartment. Notably, in both cellular compartments, differential expression of 1243aa and 1219/1300aa RTEL1 isoforms was observed. In fibroblasts, response to ionizing irradiation and non-homologous end joining were not impaired. Telomeric circles did not accumulate in patient-derived primary cells and lymphoblastoid cell lines, implying alternative pathomechanisms for telomeric loss. Overall, RTEL1-deficient cells exhibited a phenotype of replicative exhaustion, spontaneous apoptosis and senescence. Specifically, CD34+ cells failed to expand in vitro, B-cell development was compromised, and T-cells did not proliferate in long-term culture. Finally, we report on the natural history and outcome of our patients. While two patients died from infections, hematopoietic stem cell transplantation (HSCT resulted in sustained engraftment in two patients

  19. Clinical and Molecular Heterogeneity of RTEL1 Deficiency.

    Science.gov (United States)

    Speckmann, Carsten; Sahoo, Sushree Sangita; Rizzi, Marta; Hirabayashi, Shinsuke; Karow, Axel; Serwas, Nina Kathrin; Hoemberg, Marc; Damatova, Natalja; Schindler, Detlev; Vannier, Jean-Baptiste; Boulton, Simon J; Pannicke, Ulrich; Göhring, Gudrun; Thomay, Kathrin; Verdu-Amoros, J J; Hauch, Holger; Woessmann, Wilhelm; Escherich, Gabriele; Laack, Eckart; Rindle, Liliana; Seidl, Maximilian; Rensing-Ehl, Anne; Lausch, Ekkehart; Jandrasits, Christine; Strahm, Brigitte; Schwarz, Klaus; Ehl, Stephan R; Niemeyer, Charlotte; Boztug, Kaan; Wlodarski, Marcin W

    2017-01-01

    Typical features of dyskeratosis congenita (DC) resulting from excessive telomere shortening include bone marrow failure (BMF), mucosal fragility, and pulmonary or liver fibrosis. In more severe cases, immune deficiency and recurring infections can add to disease severity. RTEL1 deficiency has recently been described as a major genetic etiology, but the molecular basis and clinical consequences of RTEL1-associated DC are incompletely characterized. We report our observations in a cohort of six patients: five with novel biallelic RTEL1 mutations p.Trp456Cys, p.Ile425Thr, p.Cys1244ProfsX17, p.Pro884_Gln885ins53X13, and one with novel heterozygous mutation p.Val796AlafsX4. The most unifying features were hypocellular BMF in 6/6 and B-/NK-cell lymphopenia in 5/6 patients. In addition, three patients with homozygous mutations p.Trp456Cys or p.Ile425Thr also suffered from immunodeficiency, cerebellar hypoplasia, and enteropathy, consistent with Hoyeraal-Hreidarsson syndrome. Chromosomal breakage resembling a homologous recombination defect was detected in patient-derived fibroblasts but not in hematopoietic compartment. Notably, in both cellular compartments, differential expression of 1243aa and 1219/1300aa RTEL1 isoforms was observed. In fibroblasts, response to ionizing irradiation and non-homologous end joining were not impaired. Telomeric circles did not accumulate in patient-derived primary cells and lymphoblastoid cell lines, implying alternative pathomechanisms for telomeric loss. Overall, RTEL1-deficient cells exhibited a phenotype of replicative exhaustion, spontaneous apoptosis and senescence. Specifically, CD34 + cells failed to expand in vitro , B-cell development was compromised, and T-cells did not proliferate in long-term culture. Finally, we report on the natural history and outcome of our patients. While two patients died from infections, hematopoietic stem cell transplantation (HSCT) resulted in sustained engraftment in two patients. Whether

  20. Vitamin D deficiency in HIV-infected patients: a systematic review

    Directory of Open Access Journals (Sweden)

    Giusti A

    2011-11-01

    Full Text Available Andrea Giusti1, Giovanni Penco2, Giulio Pioli31Bone Clinic, Department of Gerontology and Musculoskeletal Sciences, Galliera Hospital, Genoa, Italy; 2Department of Infectious Diseases, Galliera Hospital, Genoa, Italy; 3Department of Geriatrics, ASMN Hospital, Reggio Emilia, ItalyAbstract: Advances in the diagnosis and management of human immunodeficiency virus (HIV have resulted in a dramatic decrease in mortality in HIV-infected individuals (HIV+. The subsequent increase in life expectancy of HIV+ has led to the need to consider the long-term complications of the disease and its treatment. Abnormalities in vitamin D status and metabolism are increasingly recognized as a major concern in HIV infection. In the last 5 years a number of cross-sectional and prospective studies have suggested a high prevalence of vitamin D deficiency in HIV+. Although few case-control studies have been published, it has been suggested that the prevalence of hypovitaminosis D in HIV+ is higher than in the general population, and at least in part, is related to the course of the disease and/or the antiretroviral drugs used to treat the disease. An adequate vitamin D status is important not only for bone tissue, but also for the global health status of HIV+ individuals, since a growing body of evidence has demonstrated the detrimental effects of vitamin D deficiency on multiple health outcomes. Therefore, definition of the size of the problem and identification of effective protocols for the prevention and management of vitamin D deficiency in HIV+ patients represent important steps in improving health status and reducing long-term chronic complications in individuals with HIV. Due to its immunomodulatory effects, vitamin D may also have implications in the progression of HIV infection. This systematic review was designed to determine the prevalence of vitamin D deficiency in HIV+ patients; to identify risk factors (related to the HIV infection or not potentially

  1. Hypercoagulability in end-stage liver disease: prevalence and its correlation with severity of liver disease and portal vein thrombosis.

    Science.gov (United States)

    Singhal, Ashish; Karachristos, Andreas; Bromberg, Michael; Daly, Ellen; Maloo, Manoj; Jain, Ashok Kumar

    2012-11-01

    Contrary to well-recognized bleeding diathesis in chronic liver disease, thrombotic events can occur in these patients due to reduction or loss of synthesis of anticoagulant proteins. Forty-seven consecutive patients with end-stage liver disease (ESLD) were investigated for activity of protein C, protein S, antithrombin, and factor V Leiden mutation. Forty-two (89.4%) patients had low levels of at least 1 while 33 (70.2%) patients were deficient for all anticoagulant proteins studied. Forty-six (97.9%) patients were negative for factor V Leiden mutation. The deficiencies were more marked in hepatitis C virus-positive patients and patients with model for end-stage liver disease (MELD) score >15. Six (12.8%) patients had portal vein thrombosis (PVT), and all had diminished protein S activity. In conclusions, deficiency of anticoagulant proteins occur in early phase of chronic liver disease. The severity of deficiency is proportional to the severity of liver disease. Despite the high prevalence of hypercoagulability, the incidence of PVT is low. Further studies with larger cohort of patients are needed to support these conclusions and to study other associated factors.

  2. Thymidine Kinase 2 Deficiency-Induced mtDNA Depletion in Mouse Liver Leads to Defect beta-Oxidation

    OpenAIRE

    Zhou, Xiaoshan; Kannisto, Kristina; Curbo, Sophie; von Dobeln, Ulrika; Hultenby, Kjell; Isetun, Sindra; Gåfvels, Mats; Karlsson, Anna

    2013-01-01

    Thymidine kinase 2 (TK2) deficiency in humans causes mitochondrial DNA (mtDNA) depletion syndrome. To study the molecular mechanisms underlying the disease and search for treatment options, we previously generated and described a TK2 deficient mouse strain (TK2(-/-)) that progressively loses its mtDNA. The TK2(-/-) mouse model displays symptoms similar to humans harboring TK2 deficient infantile fatal encephalomyopathy. Here, we have studied the TK2(-/-) mouse model to clarify the pathologica...

  3. Protein Misfolding and Human Disease

    DEFF Research Database (Denmark)

    Gregersen, Niels; Bross, Peter Gerd; Vang, Søren

    2006-01-01

    phenylketonuria, Parkinson's disease, α-1-antitrypsin deficiency, familial neurohypophyseal diabetes insipidus, and short-chain acyl-CoA dehydrogenase deficiency. Despite the differences, an emerging paradigm suggests that the cellular effects of protein misfolding provide a common framework that may contribute...

  4. Serum levels of 25-hydroxyvitamin D are associated with periodontal disease.

    Science.gov (United States)

    Laky, Markus; Bertl, Kristina; Haririan, Hady; Andrukhov, Oleh; Seemann, Rudolf; Volf, Ivo; Assinger, Alice; Gruber, Reinhard; Moritz, Andreas; Rausch-Fan, Xiaohui

    2017-06-01

    Vitamin D plays an essential role in bone metabolism as well as in immunity. Hence, it might affect the development and extent of periodontal disease. The aim of this study was the assessment of 25-hydroxyvitamin D (25(OH)D) status in periodontal disease. Twenty-nine patients with severe periodontal disease and 29 healthy volunteers were recruited in this case-control-study. Serum 25(OH)D levels, Periodontal Probing Depth (PPD), Clinical Attachment Level (CAL), Bleeding on Probing (BOP), Body Mass Index (BMI), and current smoking status and smoking history (packyears) were assessed in all participants. Serum 25(OH)D levels were compared between controls and cases. Multivariable logistic regression was used to determine the odds ratio (OR) and 95 % confidence interval (CI) for periodontal disease in 25(OH)D deficient probands. Patients with periodontal disease presented a significantly higher proportion of deficient 25(OH)D levels (i.e., periodontal disease with vitamin D deficiency was 1.5 (95 % CI, 1.13-1.98). No correlation between serum 25(OH)D levels and CAL, PPD, and BOP in the group with periodontal disease was found. In this case-control-study 25(OH)D deficiency is significantly associated with periodontal disease. The assessment of vitamin D levels in patients presenting with periodontal disease seems advisable, as vitamin D deficiency might be involved in the onset and progression of periodontal disease.

  5. Antigen-specific IgA titres after 23-valent pneumococcal vaccine indicate transient antibody deficiency disease in children

    NARCIS (Netherlands)

    Janssen, Willemijn J M; Nierkens, Stefan; Sanders, Elisabeth A; Boes, Marianne; van Montfrans, Joris M

    2015-01-01

    Paediatric patients with antibody deficiency may either be delayed in development of humoral immunity or may be persistently deficient in antibody production. To differentiate between these entities, we examined the 23-valent pneumococcal polysaccharide (PnPS) vaccine-induced IgM-, IgG- and IgA

  6. 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.

  7. Oxidative stress induces mitochondrial fragmentation in frataxin-deficient cells

    Energy Technology Data Exchange (ETDEWEB)

    Lefevre, Sophie [Mitochondria, Metals and Oxidative Stress Laboratory, Institut Jacques Monod, CNRS-Universite Paris-Diderot, Sorbonne Paris Cite, 15 rue Helene Brion, 75205 Paris cedex 13 (France); ED515 UPMC, 4 place Jussieu 75005 Paris (France); Sliwa, Dominika [Mitochondria, Metals and Oxidative Stress Laboratory, Institut Jacques Monod, CNRS-Universite Paris-Diderot, Sorbonne Paris Cite, 15 rue Helene Brion, 75205 Paris cedex 13 (France); Rustin, Pierre [Inserm, U676, Physiopathology and Therapy of Mitochondrial Disease Laboratory, 75019 Paris (France); Universite Paris-Diderot, Faculte de Medecine Denis Diderot, IFR02 Paris (France); Camadro, Jean-Michel [Mitochondria, Metals and Oxidative Stress Laboratory, Institut Jacques Monod, CNRS-Universite Paris-Diderot, Sorbonne Paris Cite, 15 rue Helene Brion, 75205 Paris cedex 13 (France); Santos, Renata, E-mail: santos.renata@ijm.univ-paris-diderot.fr [Mitochondria, Metals and Oxidative Stress Laboratory, Institut Jacques Monod, CNRS-Universite Paris-Diderot, Sorbonne Paris Cite, 15 rue Helene Brion, 75205 Paris cedex 13 (France)

    2012-02-10

    Highlights: Black-Right-Pointing-Pointer Yeast frataxin-deficiency leads to increased proportion of fragmented mitochondria. Black-Right-Pointing-Pointer Oxidative stress induces complete mitochondrial fragmentation in {Delta}yfh1 cells. Black-Right-Pointing-Pointer Oxidative stress increases mitochondrial fragmentation in patient fibroblasts. Black-Right-Pointing-Pointer Inhibition of mitochondrial fission in {Delta}yfh1 induces oxidative stress resistance. -- Abstract: Friedreich ataxia (FA) is the most common recessive neurodegenerative disease. It is caused by deficiency in mitochondrial frataxin, which participates in iron-sulfur cluster assembly. Yeast cells lacking frataxin ({Delta}yfh1 mutant) showed an increased proportion of fragmented mitochondria compared to wild-type. In addition, oxidative stress induced complete fragmentation of mitochondria in {Delta}yfh1 cells. Genetically controlled inhibition of mitochondrial fission in these cells led to increased resistance to oxidative stress. Here we present evidence that in yeast frataxin-deficiency interferes with mitochondrial dynamics, which might therefore be relevant for the pathophysiology of FA.

  8. 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.

  9. MCPIP1 deficiency in mice results in severe anemia related to autoimmune mechanisms.

    Directory of Open Access Journals (Sweden)

    Zhou Zhou

    Full Text Available Autoimmune gastritis is an organ-specific autoimmune disease of the stomach associated with pernicious anemia. The previous work from us and other groups identified MCPIP1 as an essential factor controlling inflammation and immune homeostasis. MCPIP1(-/- developed severe anemia. However, the mechanisms underlying this phenotype remain unclear. In the present study, we found that MCPIP1 deficiency in mice resulted in severe anemia related to autoimmune mechanisms. Although MCPIP1 deficiency did not affect erythropoiesis per se, the erythropoiesis in MCPIP1(-/- bone marrow erythroblasts was significantly attenuated due to iron and vitamin B12 (VB12 deficiency, which was mainly resulted from autoimmunity-associated gastritis and parietal cell loss. Consistently, exogenous supplement of iron and VB12 greatly improved the anemia phenotype of MCPIP1(-/- mice. Finally, we have evidence suggesting that autoimmune hemolysis may also contribute to anemia phenotype of MCPIP1(-/- mice. Taken together, our study suggests that MCPIP1 deficiency in mice leads to the development of autoimmune gastritis and pernicious anemia. Thus, MCPIP1(-/- mice may be a good mouse model for investigating the pathogenesis of pernicious anemia and testing the efficacy of some potential drugs for treatment of this disease.

  10. A Respiratory Syncytial Virus Vaccine Vectored by a Stable Chimeric and Replication-Deficient Sendai Virus Protects Mice without Inducing Enhanced Disease.

    Science.gov (United States)

    Wiegand, Marian Alexander; Gori-Savellini, Gianni; Gandolfo, Claudia; Papa, Guido; Kaufmann, Christine; Felder, Eva; Ginori, Alessandro; Disanto, Maria Giulia; Spina, Donatella; Cusi, Maria Grazia

    2017-05-15

    Respiratory syncytial virus (RSV) is a major cause of severe respiratory infections in children and elderly people, and no marketed vaccine exists. In this study, we generated and analyzed a subunit vaccine against RSV based on a novel genome replication-deficient Sendai virus (SeV) vector. We inserted the RSV F protein, known to be a genetically stable antigen, into our vector in a specific way to optimize the vaccine features. By exchanging the ectodomain of the SeV F protein for its counterpart from RSV, we created a chimeric vectored vaccine that contains the RSV F protein as an essential structural component. In this way, the antigen is actively expressed on the surfaces of vaccine particles in its prefusion conformation, and as recently reported for other vectored vaccines, the occurrence of silencing mutations of the transgene in the vaccine genome can be prevented. In addition, its active gene expression contributes to further stimulation of the immune response. In order to understand the best route of immunization, we compared vaccine efficacies after intranasal (i.n.) or intramuscular (i.m.) immunization of BALB/c mice. Via both routes, substantial RSV-specific immune responses were induced, consisting of serum IgG and neutralizing antibodies, as well as cytotoxic T cells. Moreover, i.n. immunization was also able to stimulate specific mucosal IgA in the upper and lower respiratory tract. In virus challenge experiments, animals were protected against RSV infection after both i.n. and i.m. immunization without inducing vaccine-enhanced disease. Above all, the replication-deficient SeV appeared to be safe and well tolerated. IMPORTANCE Respiratory syncytial virus (RSV) is a major cause of respiratory diseases in young children and elderly people worldwide. There is a great demand for a licensed vaccine. Promising existing vaccine approaches based on live-attenuated vaccines or viral vectors have suffered from unforeseen drawbacks related to immunogenicity

  11. Familial glucocorticoid deficiency presenting with generalized hyperpigmentation in an Egyptian child: a case report

    Directory of Open Access Journals (Sweden)

    Metwalley Kotb A

    2012-04-01

    Full Text Available Abstract Introduction Familial glucocorticoid deficiency, or hereditary unresponsiveness to adrenocorticotropic hormone, is a rare autosomal recessive disease characterized by glucocorticoid deficiency in the absence of mineralocorticoid deficiency. It may present in infancy or early childhood with hyperpigmentation, failure to thrive, recurrent infections, hypoglycemic attacks and convulsions that may result in coma or death. Here, we report the case of an 18-month-old Egyptian boy with familial glucocorticoid deficiency. Case presentation An 18-month-old Egyptian boy was referred to our institution for evaluation of generalized hyperpigmentation of the body associated with recurrent convulsions; one of his siblings, who had died at the age of nine months, also had generalized hyperpigmentation of the body. The initial clinical examination revealed generalized symmetrical deep hyperpigmentation of the body as well as hypotonia, normal blood pressure and normal male genitalia. He had low blood glucose and cortisol levels, normal aldosterone and high adrenocorticotropic hormone levels. Based on the above mentioned data, a provisional diagnosis of familial glucocorticoid deficiency was made, which was confirmed by a molecular genetics study. Oral hydrocortisone treatment at a dose of 10 mg/m2/day was started. The child was followed up after two months of treatment; the hyperpigmentation has lessened in comparison with his initial presentation and his blood sugar and cortisol levels were normalized. Conclusion Familial glucocorticoid deficiency is a rare, treatable disease that can be easily missed due to nonspecific presentations. The consequences of delayed diagnosis and treatment are associated with high rates of morbidity and mortality.

  12. The yeast metacaspase is implicated in oxidative stress response in frataxin-deficient cells.

    Science.gov (United States)

    Lefevre, Sophie; Sliwa, Dominika; Auchère, Françoise; Brossas, Caroline; Ruckenstuhl, Christoph; Boggetto, Nicole; Lesuisse, Emmanuel; Madeo, Frank; Camadro, Jean-Michel; Santos, Renata

    2012-01-20

    Friedreich ataxia is the most common recessive neurodegenerative disease and is caused by reduced expression of mitochondrial frataxin. Frataxin depletion causes impairment in iron-sulfur cluster and heme biosynthesis, disruption of iron homeostasis and hypersensitivity to oxidants. Currently no pharmacological treatment blocks disease progression, although antioxidant therapies proved to benefit patients. We show that sensitivity of yeast frataxin-deficient cells to hydrogen peroxide is partially mediated by the metacaspase. Metacaspase deletion in frataxin-deficient cells results in recovery of antioxidant capacity and heme synthesis. In addition, our results suggest that metacaspase is associated with mitochondrial respiration, intracellular redox control and genomic stability. Copyright © 2011 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  13. Liver failure with coagulopathy, hyperammonemia and cyclic vomiting in a toddler revealed to have combined heterozygosity for genes involved with ornithine transcarbamylase deficiency and Wilson disease.

    Science.gov (United States)

    Mira, Valerie; Boles, Richard G

    2012-01-01

    A girl with a 2 month history of cyclic episodes of vomiting, diarrhea, and lethargy lasting 2-3 days each presented with acute hepatopathy (ALT 3,500 IU/L) with coagulopathy (PT 55 s) and hyperammonemia (207 μmol/L) at age 1½ years. Biochemical and molecular analyzes revealed ornithine transcarbamylase (OTC) deficiency. While laboratory signs of mild hepatocellular dysfunction are common in OTC deficiency, substantial liver failure with coagulopathy is generally not seen, although four others cases have been reported, three of which presented with cyclic vomiting. Further evaluation in our case revealed elevated urine (198.8 μg/g creatinine) and liver (103 μg/g dry weight) copper content, and a heterozygous mutation in the Wilson disease gene, ATP7B. Our patient, now aged 5 years, has remained in excellent health with normal growth and development on fasting avoidance, a modified vegan diet, and sodium phenylbutyrate.These five cases demonstrate that generalized liver dysfunction/failure is a potential serious complication of OTC deficiency, although not a common one, and suggests that an ALT and PT should be obtained in OTC patients during episodes of hyperammonemia. Cyclic vomiting is a known presentation of OTC deficiency; it is not known if comorbid liver failure predisposes toward this phenotype. We propose that the heterozygote state in ATP7B increases the liver copper content, thus predisposing our patient with OTC deficiency to develop liver failure during a hyperammonemic episode. Our present case is an example of the opportunity of molecular diagnostics to identify putative modifier genes in patients with atypical presentations of genetic disorders.

  14. Biochemical, clinical and molecular findings in LCHAD and general mitochondrial trifunctional protein deficiency

    DEFF Research Database (Denmark)

    Olpin, S E; Clark, S; Andresen, B S

    2005-01-01

    General mitochondrial trifunctional protein (TFP) deficiency leads to a wide clinical spectrum of disease ranging from severe neonatal/infantile cardiomyopathy and early death to mild chronic progressive sensorimotor poly-neuropathy with episodic rhabdomyolysis. Isolated long-chain 3-hydroxyacyl...... major presenting feature but usually later accompanied by episodic rhabdomyolysis, is a manifestation of mild TFP protein deficiency. The mild clinical presentation and relative difficulty in diagnosis suggest that this form of TFP is probably underdiagnosed....

  15. Catch-up growth in early treated patients with growth hormone deficiency. Dutch Growth Hormone Working Group.

    OpenAIRE

    Boersma, B; Rikken, B; Wit, J M

    1995-01-01

    Catch-up growth of 26 children with growth hormone deficiency during four years of growth hormone treatment, which was started young (< 3 years), was compared with that of 16 children with coeliac disease on a gluten free diet. In children with growth hormone deficiency mean (SD) height SD score increased from -4.3 (1.8) to -1.9 (1.4) and in patients with coeliac disease from -1.8 (0.9) to -0.1 (0.8). Height SD score after four years correlated positively with injection frequency and height S...

  16. [metabonomics research on coronary heart disease patients of phlegm turbidity syndrome and qi deficiency syndrome].

    Science.gov (United States)

    Cheng, Peng; Chen, Ze-qi; Wang, Dong-sheng

    2015-02-01

    To study the correlation between Chinese medical types of coronary heart disease (CHD) [i.e., phlegm turbidity syndrome (PTS) and qi deficiency syndrome (QDS)] and their metabolites. Recruited were 65 CHD patients including 37 cases of PTS and 28 cases of QDS. Serum endogenous metabolites in the two syndrome types were determined by gas chromatograph-mass spectrometer-computer (GC/MS), and their differences between their metabolic profiles analyzed. More than 100 chromatographic peaks were totally scanned. Chromatograms obtained was matched with mass spectrum bank, and finally we got the category contribution value of 46 kinds of substances. Results of MCTree analysis showed patients of PTS and patients of QDS could be effectively distinguished. Compounds contributing to identify the two syndromes were sequenced as serine, valine, 2 hydroxy propionic acid. Comparison of metabolites showed contents of serine and 2 hydroxy propionic acid were higher in patients of PTS than in patients of QDS (Pmetabonomics of CHD TCM syndrome types could provide material bases for TCM syndrome differentiation of CHD, indicating that metabonomics technologies might become a new research method for TCM syndrome typing.

  17. Oral versus intravenous iron therapy in patients with inflammatory bowel disease and iron deficiency with and without anemia in Germany – a real-world evidence analysis

    Directory of Open Access Journals (Sweden)

    Stein J

    2018-02-01

    Full Text Available Jürgen Stein,1,2 Jennifer Scarlet Haas,3 Siew Hwa Ong,4 Kathrin Borchert,3 Thomas Hardt,5 Elmira Lechat,4 Kerry Nip,5 Douglas Foerster,4 Sebastian Braun,3 Daniel C Baumgart6 1Interdisciplinary Crohn Colitis Center Rhein-Main, Frankfurt/Main, Germany; 2Department of Gastroenterology and Clinical Nutrition, DGD Clinics Sachsenhausen, Teaching Hospital of the J.W. Goethe University, Frankfurt/Main, Germany; 3Xcenda GmbH, Hannover, Germany; 4Vifor Pharma Ltd., Glattbrugg, Switzerland; 5Vifor Pharma Deutschland GmbH, Munich, Germany; 6Division of Gastroenterology, University of Alberta, Edmonton, AB, Canada Background: Iron-deficiency anemia and iron deficiency are common comorbidities associated with inflammatory bowel disease (IBD resulting in impaired quality of life and high health care costs. Intravenous iron has shown clinical benefit compared to oral iron therapy. Aim: This study aimed to compare health care outcomes and costs after oral vs intravenous iron treatment for IBD patients with iron deficiency or iron deficiency anemia (ID/A in Germany. Methods: IBD patients with ID/A were identified by ICD-10-GM codes and newly commenced iron treatment via ATC codes in 2013 within the InGef (formerly Health Risk Institute research claims database. Propensity score matching was performed to balance both treatment groups. Non-observable covariates were adjusted by applying the difference-in-differences (DID approach. Results: In 2013, 589 IBD patients with ID/A began oral and 442 intravenous iron treatment. After matching, 380 patients in each treatment group were analyzed. The intravenous group had fewer all-cause hospitalizations (37% vs 48% and ID/A-related hospitalizations (5% vs 14% than the oral iron group. The 1-year preobservation period comparison revealed significant health care cost differences between both groups. After adjusting for cost differences by DID method, total health care cost savings in the intravenous iron group were

  18. Iron-Deficiency Anemia Leading to Transient Ischemic Attacks due to Intraluminal Carotid Artery Thrombus

    Directory of Open Access Journals (Sweden)

    H. Z. Batur Caglayan

    2013-01-01

    Full Text Available Reactive thrombocytosis secondary to iron-deficiency anemia (IDA is a rare but recognized cause of stroke. We report the case of a patient with iron-deficiency anemia presenting with multiple transient ischemic attacks (TIA due to intraluminal thrombus of an internal carotid artery. The putative mechanisms underlying anemia and stroke syndromes are not completely understood, and it is believed that iron deficiency may cause ischemic stroke by several potential mechanisms. Thrombocytosis is often associated with iron deficiency, and microcytosis produces a reduction in the red cell deformability and could produce a hypercoagulable state. The platelet count and function observed in iron-deficiency anemia could act synergistically to promote thrombus formation, especially in the setting of an underlying atherosclerotic disease. The presence of floating thrombus in a patient with clinical and MRI evidence of stroke represents a significant therapeutic dilemma and requires immediate decision about treatment.

  19. Toll-like receptor 9 suppresses lupus disease in Fas-sufficient MRL Mice.

    Directory of Open Access Journals (Sweden)

    Kevin M Nickerson

    Full Text Available Genetic deficiency in TLR9 accelerates pathogenesis in the spontaneous polygenic MRL.Faslpr murine model of systemic lupus erythematosus, despite the absence of anti-nucleosome autoantibodies. However, it could be argued that this result was dependent on Fas-deficiency rather than lupus-promoting genes in the MRL genetic background. Here we report the effects of TLR9 deficiency on autoimmune disease independent of the lpr mutation in Fas by characterizing Tlr9-/- and Tlr9+/+ mice on the Fas-intact MRL/+ genetic background. By 30 weeks of age, Tlr9-deficient MRL/+ had more severe renal disease, increased T cell activation, and higher titers of anti-Sm and anti-RNA autoantibodies than Tlr9-intact animals, as had been the case in the MRL.Faslpr model. In addition, Tlr9-deficient MRL/+ mice had increased numbers of germinal center phenotype B cells and an increase in splenic neutrophils and conventional dendritic cell populations. Thus, the disease accelerating effects of Tlr9 deficiency are separable from those mediated by the Fas mutation in the lupus-prone MRL genetic background. Nonetheless, disease acceleration in Tlr9-deficient MRL/+ mice was phenotypically distinct from that in Fas-deficient counterparts, which has important implications.

  20. Increased demyelination and axonal damage in metallothionein I+II-deficient mice during experimental autoimmune encephalomyelitis

    DEFF Research Database (Denmark)

    Penkowa, M; Espejo, C; Martínez-Cáceres, E M

    2003-01-01

    Metallothioneins I+II (MT-I+II) are antioxidant, neuroprotective factors. We previously showed that MT-I+II deficiency during experimental autoimmune encephalomyelitis (EAE) leads to increased disease incidence and clinical symptoms. Moreover, the inflammatory response of macrophages and T cells......, oxidative stress, and apoptotic cell death during EAE were increased by MT-I+II deficiency. We now show for the first time that demyelination and axonal damage are significantly increased in MT-I+II deficient mice during EAE. Furthermore, oligodendroglial regeneration, growth cone formation, and tissue...... repair including expression of trophic factors were significantly reduced in MT-I+II-deficient mice during EAE. Accordingly, MT-I+II have protective and regenerative roles in the brain....

  1. Contemporary State of the Problem of the Iodine Deficiency Elimination in the Belarus Republic

    Directory of Open Access Journals (Sweden)

    T V Mokhort

    2007-09-01

    Full Text Available The results of implementation governmental strategy of the iodine deficiency diseases elimination in the Belarus Republic based on the wide using of iodinated salt is presented. For the control of this program fulfillment more than 1300 children from 6 districts of Republic were examined. Middle Republic level of median of the urine iodine elimination for the period of the program realization has increased in more than 4 times and was equal to 179.2 ug/l and iodine deficiency decreased from 80.9 per cent in 1997 to 14.0 per cent in 2006. Consumption of iodinated salt has increased from 30.0 per cent in 1997 to 93.6 per cent in 2006. As the result the goiter rate in Belarus decreased from 17.2 per cent to 12.8 per cent. These results allow getting conclusion concerning efficiency of the strategy of using the iodinated salt recommended by the UNICEF as universal prophylaxis measure for the iodine deficiency diseases elimination.

  2. Clinically unapparent infantile thiamin deficiency in Vientiane, Laos.

    Directory of Open Access Journals (Sweden)

    Sengmanivong Khounnorath

    2011-02-01

    Full Text Available Beriberi occurs in Vientiane, Lao PDR, among breastfed infants. Clinical disease may be the tip of an iceberg with subclinical thiamin deficiency contributing to other illnesses. Thiamin treatment could improve outcome.A cohort of 778 sick infants admitted during one year without clinical evidence of beriberi were studied prospectively and erythrocyte transketolase assays (ETK performed. Biochemical thiamin deficiency was defined both in terms of the activation coefficient (α>31% and basal ETK activity 31% and 13.4 % basal ETK<0.59 micromoles/min/gHb. Infants≥2 months old had a higher frequency of biochemical markers of thiamin deficiency. Mortality was 5.5% but, among infants ≥2 months old, mortality was higher in those with basal ETK<0.59 micromoles/min/gHb (3/47, 6.4% than in those with basal ETK≥0.59 micromoles/min/gHb (1/146, 0.7% (P=0.045, relative risk=9.32 (95%CI 0.99 to 87.5. Multivariate regression analysis indicated that infant age≥2 months and fewer maternal years of schooling were independently associated with infant basal ETK<0.59 micromoles/min/gHb.Clinically unapparent thiamin deficiency is common among sick infants (≥2 months old admitted to hospital in Vientiane. This may contribute to mortality and a low clinical threshold for providing thiamin to sick infants may be needed.

  3. [Multiple facets of ADA2 deficiency: Vasculitis, auto-inflammatory disease and immunodeficiency: A literature review of 135 cases from literature].

    Science.gov (United States)

    Fayand, A; Sarrabay, G; Belot, A; Hentgen, V; Kone-Paut, I; Grateau, G; Melki, I; Georgin-Lavialle, S

    2018-04-01

    Deficiency of adenosine deaminase 2 (DADA2) is a recently described auto-inflammatory disorder. It is an autosomal recessive inherited disease, caused by mutations in the ADA2 gene (formerly known as CECR1) encoding ADA2 enzyme. Besides its role in the purine metabolism, it has been postulated that ADA2 may act as a growth factor for endothelial cells and in the differenciation of monocytes. Thus, deficiency of ADA2 would lead to endothelial damage and a skewing of monocytes into M1 pro-inflammatory macrophage, causing DADA2 manifestations. Three core clinical features have been described: inflammatory-vascular signs, hematologic abnormalities and immunodeficiency. Clinically, patients display intermittent fever, cutaneous vascular manifestations, such as livedo, ischemic strokes, arthralgia and abdominal pain crisis. Corticosteroids and immunosuppressive agents (i.e. cyclophosphamide, azathioprine, ciclosporin, methotrexate) appear to be poorly effective. Although the mechanism has not been elucidated, anti-TNF agents have been proven efficient in DADA2 and should therefore be used as first line therapy for vasculitis. Role of anti-platelet and anticoagulant therapies in stroke-prophylaxis remains to be discussed, as those patients display a high risk of intracranial bleeding. Copyright © 2017 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.

  4. Neurological Disorders in Adult Celiac Disease

    Directory of Open Access Journals (Sweden)

    Hugh J Freeman

    2008-01-01

    Full Text Available Celiac disease may initially present as a neurological disorder. Alternatively, celiac disease may be complicated by neurological changes. With impaired nutrient absorption, different deficiency syndromes may occur and these may be manifested clinically with neurological changes. However, in patients with deficiency syndromes, extensive involvement of the small intestine with celiac disease is often evident. There are a number of reports of celiac disease associated with neuropathy, ataxia, dementia and seizure disorder. In these reports, there is no clear relationship with nutrient deficiency and a precise mechanism for the neurological changes has not been defined. A small number of patients have been reported to have responded to vitamin E administration, but most do not. In some, gluten antibodies have also been described, especially in those with ataxia, but a consistent response to a gluten-free diet has not been defined. Screening for celiac disease should be considered in patients with unexplained neurological disorders, including ataxia and dementia. Further studies are needed, however, to determine if a gluten-free diet will lead to improvement in the associated neurological disorder.

  5. Carrier frequency of guanidinoacetate methyltransferase deficiency in the general population by functional characterization of missense variants in the GAMT gene

    NARCIS (Netherlands)

    Desroches, C.L.; Patel, J.; Wang, P.X.; Minassian, B.; Marshall, C.R.; Salomons, G.; Mercimek-Mahmutoglu, S.

    2015-01-01

    Guanidinoacetate methyltransferase (GAMT) deficiency is a neurodegenerative disease. Although no symptomatic patients on treatment achieved normal neurodevelopment, three asymptomatic newborns were reported with normal neurodevelopmental outcome on neonatal treatment. GAMT deficiency is therefore a

  6. Vitamin B12 Deficiency in Relation to Functional Disabilities

    Directory of Open Access Journals (Sweden)

    Heather E. Rasmussen

    2013-11-01

    Full Text Available This study was designed to assess whether symptoms, functional measures, and reported disabilities were associated with vitamin B12 (B12 deficiency when defined in three ways. Participants, aged 60 or more years of age, in 1999–2002 National Health and Nutrition Examination Surveys (NHANES were categorized in relation to three previously used definitions of B12 deficiency: (1 serum B12 20 μmol/L; and (3 serum B12 0.21 μmol/L. Functional measures of peripheral neuropathy, balance, cognitive function, gait speed, along with self-reported disability (including activities of daily living were examined with standardized instruments by trained NHANES interviewers and technicians. Individuals identified as B12 deficient by definition 2 were more likely to manifest peripheral neuropathy OR (odds (95% confidence intervals, p value: 9.70 (2.24, 42.07, 0.004 and report greater total disability, 19.61 (6.22, 61.86 0.0001 after adjustments for age, sex, race, serum creatinine, and ferritin concentrations, smoking, diabetes, and peripheral artery disease. Smaller, but significantly increased, odds of peripheral neuropathy and total disability were also observed when definition 3 was applied. Functional measures and reported disabilities were associated with B12 deficiency definitions that include B12 biomarkers (homocysteine or methylmalonic acid. Further study of these definitions is needed to alert clinicians of possible subclinical B12 deficiency because functional decline amongst older adults may be correctable if the individual is B12 replete.

  7. 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 ...

  8. DIAGNOSTICS AND TREATMENT OF EXCRETORY DEFICIENCY OF PANCREAS IN CHILDREN

    Directory of Open Access Journals (Sweden)

    S.V. Bel’mer

    2009-01-01

    Full Text Available Excretory pancreatic insufficiency is relatively frequent pathology in pediatric and therapeutic practice. It can be divided to primary and secondary, inborn and acquired, absolute and relative one. The causes of primary pancreatic insufficiency are agenesia or hypoplasia of pancreas, cystic fibrosis, Shwachman–Diamond syndrome. Secondary excretory pancreatic insufficiency can be caused by resection of pancreas, pancreatitis, pathology of mucous tunic of small intestine, abnormality of antitrypsinactivation with enterokinase deficiency, inactivation of enzymes by acid of duodenal contents in the presence of gastric hyper secretion and others. Excretory pancreatic deficiency has determined clinical signs and can be relatively easily diagnosed by simple laboratory methods: coprogramm and detection of elastase 1 in stool. The ways of its correction are determined by causes of disease, but modern high-active pancreatic enzymes medications must be necessary component of treatment in all cases.Key words: children, pancreatic insufficiency, celiac disease, pancreatic enzymes medications.(Voprosy sovremennoi pediatrii — Current Pediatrics. 2009;8(2:114-118

  9. Apolipoprotein E deficiency increases remnant lipoproteins and accelerates progressive atherosclerosis, but not xanthoma formation, in gene modified minipigs

    DEFF Research Database (Denmark)

    Shim, Jeong; Poulsen, Christian Bo; Hagensen, Mette K.

    2017-01-01

    Summary: Deficiency of apolipoprotein E (APOE) causes familial dysbetalipoproteinemia in humans resulting in a higher risk of atherosclerotic disease. In mice, APOE deficiency results in a severe atherosclerosis phenotype, but it is unknown to what extent this is unique to mice. In this study, AP...

  10. [EFFICACY OF IVIG TREATMENT IN BRONCHIECTASIS ASSOCIATED WITH IGG SUBCLASS DEFICIENCY].

    Science.gov (United States)

    Shostak, Yael; Kramer, Mordechai R

    2017-11-01

    Bronchiectasis is characterized by an abnormal dilatation of the bronchi leading to a chronic inflammatory process, airway blockage and impaired clearance of secretions. The damage to the airways is usually progressive and is the result of several pathogenic processes. In the past, healing of infections (especially pulmonary tuberculosis) was the main cause of airway dilatation and progression of chronic inflammation. Today, congenital illnesses, anatomical defects and immune deficiency play an important role in the pathogenesis of bronchiectasis formation. The immunoglobulin repertoire is vital for effective host protection against a wide variety of pathogens. Primary antibody deficiency diseases are defects of the humoral arm of the immune system and involve an absence/reduced levels of one or more immunoglobulin classes/subclasses or defects of specific antibody formation. Immunoglobulin G (IGG) subclass deficiency can occur in a healthy person and could be without clinical significance. However, in recent years there is emerging evidence that in patients with recurrent infections, early diagnosis of antibody deficiency affects the prognosis and prevention of ongoing lung damage. The use of IVIG has contributed significantly to the survival rate in primary antibody deficiencies. There is limited literature on the treatment of IVIG for patients with IGG subclass deficiency. However, all studies presented so far demonstrated that immunoglobulin therapy reduced the rate of bacterial infections, days of antibiotic usage, hospital admissions and significantly increased patients' quality of life. Therefore, in the appropriate clinical setting, ie: a patient with bronchiectasis and recurrent infections, it is justified to test whether there are humoral immune defects such as IGG subclass deficiency. In a patient with proven deficiency, we should recommend to start IVIG treatment until clinical benefit is achieved.

  11. Mechanism of testosterone deficiency in the transgenic sickle cell mouse.

    Directory of Open Access Journals (Sweden)

    Biljana Musicki

    Full Text Available Testosterone deficiency is associated with sickle cell disease (SCD, but its underlying mechanism is not known. We investigated the possible occurrence and mechanism of testosterone deficiency in a mouse model of human SCD. Transgenic sickle male mice (Sickle exhibited decreased serum and intratesticular testosterone and increased luteinizing hormone (LH levels compared with wild type (WT mice, indicating primary hypogonadism in Sickle mice. LH-, dbcAMP-, and pregnenolone- (but not 22-hydroxycholesterol- stimulated testosterone production by Leydig cells isolated from the Sickle mouse testis was decreased compared to that of WT mice, implying defective Leydig cell steroidogenesis. There also was reduced protein expression of steroidogenic acute regulatory protein (STAR, but not cholesterol side-chain cleavage enzyme (P450scc, in the Sickle mouse testis. These data suggest that the capacity of P450scc to support testosterone production may be limited by the supply of cholesterol to the mitochondria in Sickle mice. The sickle mouse testis exhibited upregulated NADPH oxidase subunit gp91phox and increased oxidative stress, measured as 4-hydroxy-2-nonenal, and unchanged protein expression of an antioxidant glutathione peroxidase-1. Mice heterozygous for the human sickle globin (Hemi exhibited intermediate hypogonadal changes between those of WT and Sickle mice. These results demonstrate that testosterone deficiency occurs in Sickle mice, mimicking the human condition. The defects in the Leydig cell steroidogenic pathway in Sickle mice, mainly due to reduced availability of cholesterol for testosterone production, may be related to NADPH oxidase-derived oxidative stress. Our findings suggest that targeting testicular oxidative stress or steroidogenesis mechanisms in SCD offers a potential treatment for improving phenotypic changes associated with testosterone deficiency in this disease.

  12. 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

  13. Small for Gestational Age and Magnesium: Intrauterine magnesium deficiency may induce metabolic syndrome in later life

    Directory of Open Access Journals (Sweden)

    Junji Takaya

    2015-12-01

    Full Text Available Magnesium deficiency during pregnancy as a result of insufficient or low intake of magnesium is common in developing and developed countries. Previous reports have shown that intracellular magnesium of cord blood platelets is lower among small for gestational age (SGA groups than that of appropriate for gestational age (AGA groups, suggesting that intrauterine magnesium deficiency may result in SGA. Additionally, the risk of adult-onset diseases such as insulin resistance syndrome is greater among children whose mothers were malnourished during pregnancy, and who consequently had a low birth weight. In a number of animal models, poor nutrition during pregnancy leads to offspring that exhibit pathophysiological changes similar to human diseases. The offspring of pregnant rats fed a magensium restricted diet have developed hypermethylation in the hepatic 11β-hydroxysteroid dehydrogenase-2 promoter. These findings indicate that maternal magnesium deficiencies during pregnancy influence regulation of non-imprinted genes by altering the epigenetic regulation of gene expression, thereby inducing different metabolic phenotypes. Magnesium deficiency during pregnancy may be responsible for not only maternal and fetal nutritional problems, but also lifelong consequences that affect the offspring throughout their life. Epidemiological, clinical, and basic research on the effects of magnesium deficiency now indicates underlying mechanisms, especially epigenetic processes.

  14. Metaherpetic corneal disease in a dog associated with partial limbal stem cell deficiency and neurotrophic keratitis.

    Science.gov (United States)

    Ledbetter, Eric C; Marfurt, Carl F; Dubielzig, Richard R

    2013-07-01

    To describe clinical, in vivo confocal microscopic, histopathologic, and immunohistochemical features of a dog with metaherpetic corneal disease that developed subsequent to a protracted episode of canine herpesvirus-1 (CHV-1) dendritic ulcerative keratitis. A 7-year-old, spayed-female, Miniature Schnauzer was treated for bilateral CHV-1 dendritic ulcerative keratitis. Following resolution of ulcerative keratitis, sectoral peripheral superficial corneal gray opacification, vascularization, and pigmentation slowly migrated centripetally to the axial cornea of both eyes. Corneal sensitivity measured with a Cochet-Bonnet esthesiometer was dramatically and persistently reduced. In vivo corneal confocal microscopic examination revealed regions of epithelium with a conjunctival phenotype. In these areas, the surface epithelium was thin, disorganized, and composed of hyper-reflective epithelial cells. Goblet cells and Langerhans cells were frequent, and the subbasal nerve plexus was completely absent or markedly diminished. Histopathologic abnormalities in the globes were restricted to the superficial cornea and included sectoral corneal conjunctivalization, increased anterior stromal spindle cells, and vascularization. Immunohistochemical evaluation of the corneas with anti-neurotublin antibody demonstrated attenuation of the epithelial and subbasal nerve plexuses with marked stromal hyperinnervation and increased numbers of morphologically abnormal neurites. Similar to herpes simplex virus keratitis in humans, CHV-1 ulcerative keratitis may be associated with the development of chronic degenerative corneal disease in dogs. In the described dog, this chronic corneal disease included progressive corneal opacification because of partial limbal stem cell deficiency and neurotrophic keratitis. Long-term monitoring of dogs following resolution of active CHV-1 keratitis may be indicated, particularly when ulcerations persist for an extended period. © 2012 American College of

  15. Vitamin D Deficiency in India: Prevalence, Causalities and Interventions

    Directory of Open Access Journals (Sweden)

    Ritu G

    2014-02-01

    Full Text Available Vitamin D deficiency prevails in epidemic proportions all over the Indian subcontinent, with a prevalence of 70%–100% in the general population. In India, widely consumed food items such as dairy products are rarely fortified with vitamin D. Indian socioreligious and cultural practices do not facilitate adequate sun exposure, thereby negating potential benefits of plentiful sunshine. Consequently, subclinical vitamin D deficiency is highly prevalent in both urban and rural settings, and across all socioeconomic and geographic strata. Vitamin D deficiency is likely to play an important role in the very high prevalence of rickets, osteoporosis, cardiovascular diseases, diabetes, cancer and infections such as tuberculosis in India. Fortification of staple foods with vitamin D is the most viable population based strategy to achieve vitamin D sufficiency. Unfortunately, even in advanced countries like USA and Canada, food fortification strategies with vitamin D have been only partially effective and have largely failed to attain vitamin D sufficiency. This article reviews the status of vitamin D nutrition in the Indian subcontinent and also the underlying causes for this epidemic. Implementation of population based educational and interventional strategies to combat this scourge require recognition of vitamin D deficiency as a public health problem by the governing bodies so that healthcare funds can be allocated appropriately.

  16. Dystrophin deficiency leads to disturbance of LAMP1-vesicle-associated protein secretion

    DEFF Research Database (Denmark)

    Duguez, S.; Duddy, W.; Johnston, H.

    2013-01-01

    Duchenne muscular dystrophy results from loss of the protein dystrophin, which links the intracellular cytoskeletal network with the extracellular matrix, but deficiency in this function does not fully explain the onset or progression of the disease. While some intracellular events involved...... in the degeneration of dystrophin-deficient muscle fibers have been well characterized, changes in their secretory profile are undescribed. To analyze the secretome profile of mdx myotubes independently of myonecrosis, we labeled the proteins of mdx and wild-type myotubes with stable isotope-labeled amino acids...

  17. [Plasma metabonomics of Guifu Dihuang Wan in the treatment of yang deficiency].

    Science.gov (United States)

    Xiao, Ya; Jing, Yuan; Chen, Jie-Yu; Li, Fei; Cheng, Jing-Ru; Bi, Jian-Lu; Luo, Ren; Zhao, Xiao-Shan

    2016-11-20

    To assess the effect of Guifu Dihuang Wan (GFDHW) in the treatment of yang deficiency and explore the underlying molecular mechanism. Sixty-two participants without diseases were randomized into control group (n=31) and experimental group (n=31) and were given lifestyle intervention additional GFDHW treatment for a month. NMR technology was used for metabonomics analysis. Intervention with GFDHW resulted in significantly decreased conversion scores of yang deficiency in the experimental group compared with the control group (P<0.005). The concentrations of lactate, valine, proline, arginine and 3-hydroxybutyrate were increased in the plasma of yang-deficient subjects after lifestyle intervention. GFDHW treatment with lifestyle intervention significantly increased the concentrations of lactate, valine, proline, arginine and 3-hydroxybutyrate and also the levels of alanine, glutamine, alpha glucose, isoleucine, betaine and propylene glycol. GFDHW treatment improves yang deficiency possibly by increasing the concentrations of alanine, glutamine, alpha glucose, isoleucine, betaine and propylene glycol and promoting energy metabolism of the body.

  18. Screening for C3 deficiency in newborns using microarrays.

    Directory of Open Access Journals (Sweden)

    Magdalena Janzi

    Full Text Available BACKGROUND: Dried blood spot samples (DBSS from newborns are widely used in neonatal screening for selected metabolic diseases and diagnostic possibilities for additional disorders are continuously being evaluated. Primary immunodeficiency disorders comprise a group of more than one hundred diseases, several of which are fatal early in life. Yet, a majority of the patients are not diagnosed due to lack of high-throughput screening methods. METHODOLOGY/PRINCIPAL FINDINGS: We have previously developed a system using reverse phase protein microarrays for analysis of IgA levels in serum samples. In this study, we extended the applicability of the method to include determination of complement component C3 levels in eluates from DBSS collected at birth. Normal levels of C3 were readily detected in 269 DBSS from healthy newborns, while no C3 was detected in sera and DBSS from C3 deficient patients. CONCLUSIONS/SIGNIFICANCE: The findings suggest that patients with deficiencies of specific serum proteins can be identified by analysis of DBSS using reverse phase protein microarrays.

  19. IL-25 inhibits atherosclerosis development in apolipoprotein E deficient mice.

    Directory of Open Access Journals (Sweden)

    Polyxeni T Mantani

    Full Text Available IL-25 has been implicated in the initiation of type 2 immunity and in the protection against autoimmune inflammatory diseases. Recent studies have identified the novel innate lymphoid type 2 cells (ILC2s as an IL-25 target cell population. The purpose of this study was to evaluate if IL-25 has any influence on atherosclerosis development in mice.Administration of 1 μg IL-25 per day for one week to atherosclerosis-prone apolipoprotein (apoE deficient mice, had limited effect on the frequency of T cell populations, but resulted in a large expansion of ILC2s in the spleen. The expansion was accompanied by increased levels of anti-phosphorylcholine (PC natural IgM antibodies in plasma and elevated levels of IL-5 in plasma and spleen. Transfer of ILC2s to apoE deficient mice elevated the natural antibody-producing B1a cell population in the spleen. Treatment of apoE/Rag-1 deficient mice with IL-25 was also associated with extensive expansion of splenic ILC2s and increased plasma IL-5, suggesting ILC2s to be the source of IL-5. Administration of IL-25 in IL-5 deficient mice resulted in an expanded ILC2 population, but did not stimulate generation of anti-PC IgM, indicating that IL-5 is not required for ILC2 expansion but for the downstream production of natural antibodies. Additionally, administration of 1 μg IL-25 per day for 4 weeks in apoE deficient mice reduced atherosclerosis in the aorta both during initiation and progression of the disease.The present findings demonstrate that IL-25 has a protective role in atherosclerosis mediated by innate responses, including ILC2 expansion, increased IL-5 secretion, B1a expansion and natural anti-PC IgM generation, rather than adaptive Th2 responses.

  20. A novel encephalopathy in a thiamine-deficient dog resembling human Wernicke’s disease with atypical MRI pattern

    Directory of Open Access Journals (Sweden)

    Floriana Gernone

    2017-11-01

    Full Text Available Thiamine is a water-soluble vitamin, which participates in several vital metabolic pathways involved in energy metabolism and neurotransmitter synthesis of mammals. In companion animals thiamine deficiency is classically associated with signs of diffuse encephalopathy and lesions on brainstem nuclei and mesencephalic colliculi evident on magnetic resonance imaging. This paper describes a novel clinical presentation in a thiamine-deficient dog showing multifocal, central and peripheral nervous and cardiovascular system alterations. Brain MRI showed bilateral caudate nuclei damage, with necrotic-malacic evolution, similar to the atypical MRI pattern found in Wernicke’s encephalopathy in humans. Detection of bilateral symmetrical lesions of the caudate nuclei in dogs should prompt consideration of a thiamine deficiency among the differential diagnoses.

  1. Proximal focal femoral deficiency: A case report

    Directory of Open Access Journals (Sweden)

    Shashank Sharma

    2015-01-01

    Full Text Available Proximal focal femoral deficiency (PFFD is a rare congenital anomaly resulting in limb shortening and disability in young. The exact cause of the disease is not known and it may present as varying grades of affection involving the proximal femur and the acetabulum. Recognition of this rare abnormality on radiographs can help manage these cases better since early institution of therapy may help in achieving adequate growth of the femur.

  2. Childhood Interstitial Lung Disease

    Science.gov (United States)

    ... rule out conditions such as asthma , cystic fibrosis , acid reflux, heart disease, neuromuscular disease, and immune deficiency. Various ... a lung infection. Acid-blocking medicines can prevent acid reflux, which can lead to aspiration. Lung Transplant A ...

  3. HASHIMOTO THYROIDITIS NOT ASSOCIATED WITH VITAMIN D DEFICIENCY.

    Science.gov (United States)

    Yasmeh, Joseph; Farpour, Farzin; Rizzo, Vincent; Kheradnam, Sharon; Sachmechi, Issac

    2016-07-01

    Vitamin D deficiency is associated with several autoimmune diseases. This study assessed whether vitamin D deficiency is associated with Hashimoto thyroiditis (HT). Two groups of patients were selected for which serum 25-hydroxyvitamin D (25(OH)D) levels had been measured: (1) a study group of patients diagnosed with HT as indicated by thyroid antibodies, and (2) a healthy control group. Each group was separated by sex and then controlled for age and body mass index (BMI). Groups' mean 25(OH)D levels were compared by analysis of variance (ANOVA), and percent frequencies of vitamin D sufficiency, insufficiency, and deficiency were compared with a Z-test. The correlations between 25(OH)D levels and thyroid antibodies and thyroid-stimulating hormone (TSH) levels were also tested. The mean 25(OH)D levels for the HT and control groups were significantly different in females (30.75 vs. 27.56 ng/mL, respectively) but not in males (14.24 vs. 13.26 ng/mL). HT females had a higher rate of vitamin D sufficiency (51.7% vs. 31.1%) and a lower rate of insufficiency (48.3% vs. 68.9%) relative to control females. No such differences were found in the male groups. None of the females were vitamin D deficient, but almost all males were. A significant (P = .016) positive correlation (rs = 0.436) between 25(OH)D and TPOAb was observed in males. HT is not associated with higher rates of vitamin D deficiency relative to a control group. BMI = body mass index HT = Hashimoto thyroiditis 25(OH)D = 25-hydroxyvitamin D TgAb = thyroglobulin antibody TSH = thyroid-stimulating hormone TPOAb = thyroid-peroxidase antibody VDR = Vitamin D receptor.

  4. 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

  5. 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).

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

    Directory of Open Access Journals (Sweden)

    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.

  7. 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 ...

  8. Iron-Deficiency Anemia

    Medline Plus

    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 ...

  9. 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...

  10. The prevalence of vitamin D deficiency in consecutive new patients seen over a 6-month period in general rheumatology clinics.

    LENUS (Irish Health Repository)

    Haroon, Muhammad

    2012-02-01

    The objectives of this study are to assess: (a) the prevalence of vitamin D deficiency among new patients attending rheumatology outpatient departments, (b) the age profile of these low vitamin D patients and (c) whether any diagnostic category had a particularly high number of vitamin D-deficient patients. All new patients seen consecutively in general rheumatology clinics between January to June 2007 inclusive were eligible to partake in this study, and 231 out of 264 consented to do so. Parathyroid hormone, 25-hydroxyvitamin D, creatinine, calcium, phosphate, albumin and alkaline phosphatase levels were measured. We defined vitamin D deficiency as <\\/=53 nmol\\/l and severe deficiency as <\\/=25 nmol\\/l. Overall, 70% of 231 patients had vitamin D deficiency, and 26% had severe deficiency. Sixty-five percent of patients aged >\\/=65 and 78% of patients aged <\\/=30 years had low vitamin D levels. Vitamin D deficiency in each diagnostic category was as follows: (a) inflammatory joint diseases\\/connective tissue diseases (IJD\\/CTD), 69%; (b) soft tissue rheumatism, 77%; (c) osteoarthritis, 62%; (d) non-specific musculoskeletal back pain, 75% and (e) osteoporosis, 71%. Seasonal variation of vitamin D levels was noted in all diagnostic groups apart from IJD\\/CTD group, where the degree of vitamin D deficiency persisted from late winter to peak summer. Very high prevalence of vitamin D deficiency was noted in all diagnostic categories (p = 0.006), and it was independent of age (p = 0.297). The results suggest vitamin D deficiency as a possible modifiable risk factor in different rheumatologic conditions, and its role in IJD\\/CTD warrants further attention.

  11. 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 ...

  12. 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 ...

  13. Impact of Ecologically Unfriendly Environment on the Formation of Thyroid Pathology in Children Against Iodine Deficiency

    Directory of Open Access Journals (Sweden)

    N.S. Kosmynina

    2014-02-01

    Full Text Available By prevalence among thyroid pathological conditions in Ukraine, the diffuse nontoxic goiter is dominated, the frequency of which, in addition to iodine deficiency, is influenced by anthropogenic pollution of environment. The article evaluated the role of the negative impact of polluted environment on the formation of thyroid disease in children from ecologically unfriendly region on the background of endemic iodine deficiency compared with children from ecologically friendly area of iodine deficiency. It has been determined the frequency of diffuse endemic goiter in children from studied groups according to palpation and ultrasonography. The functional state of the pituitary-thyroid system in children living in iodine deficiency environmentally unfriendly and ecologically friendly areas has been researched.

  14. Affective and cognitive behavior in the alpha-galactosidase A deficient mouse model of Fabry disease.

    Directory of Open Access Journals (Sweden)

    Lukas Hofmann

    Full Text Available Fabry disease is an X-linked inherited lysosomal storage disorder with intracellular accumulation of globotriaosylceramide (Gb3 due to α-galactosidase A (α-Gal A deficiency. Fabry patients frequently report of anxiety, depression, and impaired cognitive function. We characterized affective and cognitive phenotype of male mice with α-Gal A deficiency (Fabry KO and compared results with those of age-matched male wildtype (WT littermates. Young (3 months and old (≥ 18 months mice were tested in the naïve state and after i.pl. injection of complete Freund`s adjuvant (CFA as an inflammatory pain model. We used the elevated plus maze (EPM, the light-dark box (LDB and the open field test (OF to investigate anxiety-like behavior. The forced swim test (FST and Morris water maze (MWM were applied to assess depressive-like and learning behavior. The EPM test revealed no intergroup difference for anxiety-like behavior in naïve young and old Fabry KO mice compared to WT littermates, except for longer time spent in open arms of the EPM for young WT mice compared to young Fabry KO mice (p<0.05. After CFA injection, young Fabry KO mice showed increased anxiety-like behavior compared to young WT littermates (p<0.05 and naïve young Fabry KO mice (p<0.05 in the EPM as reflected by shorter time spent in EPM open arms. There were no relevant differences in the LDB and the OF test, except for longer time spent in the center zone of the OF by young WT mice compared to young Fabry KO mice (p<0.05. Complementary to this, depression-like and learning behavior were not different between genotypes and age-groups, except for the expectedly lower memory performance in older age-groups compared to young mice. Our results indicate that genetic influences on affective and cognitive symptoms in FD may be of subordinate relevance, drawing attention to potential influences of environmental and epigenetic factors.

  15. Quadruple burden of HIV/AIDS, tuberculosis, chronic intestinal parasitoses, and multiple micronutrient deficiency in ethiopia: a summary of available findings.

    Science.gov (United States)

    Amare, Bemnet; Moges, Beyene; Mulu, Andargachew; Yifru, Sisay; Kassu, Afework

    2015-01-01

    Human immunodeficiency virus (HIV), tuberculosis (TB), and helminthic infections are among the commonest public health problems in the sub-Saharan African countries like Ethiopia. Multiple micronutrient deficiencies also known as the "hidden hunger" are common in people living in these countries either playing a role in their pathogenesis or as consequences. This results in a vicious cycle of multiple micronutrient deficiencies and infection/disease progression. As infection is profoundly associated with nutritional status resulting from decreased nutrient intake, decreased nutrient absorption, and nutrient losses, micronutrient deficiencies affect immune system and impact infection and diseases progression. As a result, micronutrients, immunity, and infection are interrelated. The goal of this review is therefore to provide a summary of available findings regarding the "quadruple burden trouble" of HIV, TB, intestinal parasitic infections, and multiple micronutrient deficiencies to describe immune-modulating effects related to disorders.

  16. Combinatorial effects of zinc deficiency and arsenic exposure on zebrafish (Danio rerio development.

    Directory of Open Access Journals (Sweden)

    Laura M Beaver

    Full Text Available Zinc deficiency and chronic low level exposures to inorganic arsenic in drinking water are both significant public health concerns that affect millions of people including pregnant women. These two conditions can co-exist in the human population but little is known about their interaction, and in particular, whether zinc deficiency sensitizes individuals to arsenic exposure and toxicity, especially during critical windows of development. To address this, we utilized the Danio rerio (zebrafish model to test the hypothesis that parental zinc deficiency sensitizes the developing embryo to low-concentration arsenic toxicity, leading to altered developmental outcomes. Adult zebrafish were fed defined zinc deficient and zinc adequate diets and were spawned resulting in zinc adequate and zinc deficient embryos. The embryos were treated with environmentally relevant concentrations of 0, 50, and 500 ppb arsenic. Arsenic exposure significantly reduced the amount of zinc in the developing embryo by ~7%. The combination of zinc deficiency and low-level arsenic exposures did not sensitize the developing embryo to increased developmental malformations or mortality. The combination did cause a 40% decline in physical activity of the embryos, and this decline was significantly greater than what was observed with zinc deficiency or arsenic exposure alone. Significant changes in RNA expression of genes that regulate zinc homeostasis, response to oxidative stress and insulin production (including zip1, znt7, nrf2, ogg1, pax4, and insa were found in zinc deficient, or zinc deficiency and arsenic exposed embryos. Overall, the data suggests that the combination of zinc deficiency and arsenic exposure has harmful effects on the developing embryo and may increase the risk for developing chronic diseases like diabetes.

  17. Increased periodontal bone loss in temporarily B lymphocyte-deficient rats

    DEFF Research Database (Denmark)

    Klausen, B; Hougen, H P; Fiehn, N E

    1989-01-01

    In order to study the role of T lymphocytes and B lymphocytes in the development of marginal periodontitis, experiments were performed on specific-pathogen-free (SPF) rats with various immunologic profiles. The study comprised nude (congenitally T lymphocyte-deficient), thymus-grafted nude (T-lym......-lymphocyte deficiency did not interfere with the development of periodontal disease in this model, whereas a temporary and moderate reduction in B-lymphocyte numbers seemed to predispose for aggravation of periodontal bone loss.......In order to study the role of T lymphocytes and B lymphocytes in the development of marginal periodontitis, experiments were performed on specific-pathogen-free (SPF) rats with various immunologic profiles. The study comprised nude (congenitally T lymphocyte-deficient), thymus-grafted nude (T...... had significantly less periodontal bone support than controls. Anti-mu treated inoculated rats had significantly less periodontal bone support than nude and normal rats, whereas no difference was found between normal, nude, and thymus-grafted rats. It is concluded that permanent T...

  18. Identification of two novel mutations in OCTN2 from two Saudi patients with systemic carnitine deficiency

    NARCIS (Netherlands)

    Rahbeeni, Z.; Vaz, F. M.; Al-Hussein, K.; Bucknall, M. P.; Ruiter, J.; Wanders, R. J.; Rashed, M. S.

    2002-01-01

    Systemic carnitine deficiency (CDSP) (McKusick 212140) is a rare autosomal recessive disease caused by defective plasma membrane uptake of carnitine. The disease is characterized by Reye syndrome, progressive cardiomyopathy, skeletal myopathy, hypoglycaemia and hyperammonaemia. CDSP is a treatable

  19. Factors Associated with Vitamin D Testing, Deficiency, Intake, and Supplementation in Patients with Chronic Pain.

    Science.gov (United States)

    Gaikwad, Manasi; Vanlint, Simon; Moseley, G Lorimer; Mittinty, Murthy N; Stocks, Nigel

    2017-11-02

    Vitamin D deficiency is a public health issue, with reports of six- to twenty-five-fold rise in vitamin D testing. Vitamin D deficiency has been linked to many chronic diseases such as diabetes mellitus, cardiovascular disease, depression, and chronic pain. Identifying factors associated with risk of deficiency in individuals with chronic pain will help minimize time and cost. This study aims to examine the factors associated with vitamin D testing, intake, and physician-advised supplementation in individuals with chronic pain. Using a cross-sectional design, data were collected from 465 individuals with chronic pain. These data were analyzed using penalized logistic regression with the LASSO technique. Fifty-seven percent reported being tested for vitamin D, about 40% reported being diagnosed with vitamin D deficiency, and of those who had been tested, 60% reported taking vitamin D supplementation. The findings suggest older age (OR 3.12, CI [1.02, 9.50]) and higher mean pain intensity score (OR 2.02, CI [1.13, 3.59]) increased an individual's chance of being vitamin D deficient. Unemployment or on leave due to pain (OR 1.79, [CI 1.03, 3.11]), part-time employment (OR 1.86, CI [1.02, 3.39]), and being a resident of Australia (OR 2.32, CI [1.13, 4.72]) increased chances of being tested for vitamin D. Being diagnosed with vitamin D deficiency (OR 6.67, CI [2.75, 16.19]), unemployed or on leave due to pain (OR 3.71, CI [1.25, 11.00]), and in part-time employment (OR 2.69, CI [0.86, 8.38]) were associated with physician-advised vitamin D supplementation. Our results may have practical implications, as identifying pretest risk factors may assist in identifying who is at risk of vitamin D deficiency, whom to test, and when to treat.

  20. Disease: H01582 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available nal deficiencies, like alcoholism. Metabolic disorders; Nervous system disease; Skin disease ... Nicotinami...no acid precursor tryptophan. ... It is currently seen in association with other conditions of chronic nutritio

  1. Coenzyme Q10 defects may be associated with a deficiency of Q10-independent mitochondrial respiratory chain complexes

    Directory of Open Access Journals (Sweden)

    Konstantina Fragaki

    Full Text Available BACKGROUND: Coenzyme Q10 (CoQ10 or ubiquinone deficiency can be due either to mutations in genes involved in CoQ10 biosynthesis pathway, or to mutations in genes unrelated to CoQ10 biosynthesis. CoQ10 defect is the only oxidative phosphorylation disorder that can be clinically improved after oral CoQ10 supplementation. Thus, early diagnosis, first evoked by mitochondrial respiratory chain (MRC spectrophotometric analysis, then confirmed by direct measurement of CoQ10 levels, is of critical importance to prevent irreversible damage in organs such as the kidney and the central nervous system. It is widely reported that CoQ10 deficient patients present decreased quinone-dependent activities (segments I + III or G3P + III and II + III while MRC activities of complexes I, II, III, IV and V are normal. We previously suggested that CoQ10 defect may be associated with a deficiency of CoQ10-independent MRC complexes. The aim of this study was to verify this hypothesis in order to improve the diagnosis of this disease. RESULTS: To determine whether CoQ10 defect could be associated with MRC deficiency, we quantified CoQ10 by LC-MSMS in a cohort of 18 patients presenting CoQ10-dependent deficiency associated with MRC defect. We found decreased levels of CoQ10 in eight patients out of 18 (45 %, thus confirming CoQ10 disease. CONCLUSIONS: Our study shows that CoQ10 defect can be associated with MRC deficiency. This could be of major importance in clinical practice for the diagnosis of a disease that can be improved by CoQ10 supplementation.

  2. Protein misfolding and obstructive lung disease.

    LENUS (Irish Health Repository)

    Greene, Catherine M

    2010-11-01

    The endoplasmic reticulum has evolved a number of mechanisms to manage the accumulation of incorrectly folded proteins. This results in loss of function of these proteins, but occasionally, in conditions such as α-1 antitrpysin (A1AT) deficiency, the misfolded protein can acquire a toxic gain of function promoting exaggerated ER stress responses and inflammation. Mutations leading to deficiency in a second serine proteinase inhibitor, α-1 antichymotrpysin (ACT), can induce potentially similar consequences. A1AT and ACT deficiencies are associated with chronic obstructive lung disease. Until recently, it was thought that the lung diseases associated with these conditions were entirely due to loss of antiprotease protection in the lung (i.e., loss of function), whereas gain of function was the major cause of the liver disease associated with A1AT deficiency. This paradigm is being increasingly challenged because ER stress is being recognized in bronchial epithelial cells and inflammatory cells normally resident in the lung, giving rise to an inflammatory phenotype that adds to the proteolytic burden associated with these conditions. In this article, we describe the cellular mechanisms that are activated to cope with an increasing burden of misfolded proteins within the ER in A1AT and ACT deficiency, show how these events are linked to inflammation, and outline the therapeutic strategies that can potentially interfere with production of misfolded proteins.

  3. 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.

  4. 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

  5. Narcolepsy with hypocretin/orexin deficiency, infections and autoimmunity of the brain

    DEFF Research Database (Denmark)

    Kornum, Birgitte Rahbek; Faraco, Juliette; Mignot, Emmanuel

    2011-01-01

    The loss of hypothalamic hypocretin/orexin (hcrt) producing neurons causes narcolepsy with cataplexy. An autoimmune basis for the disease has long been suspected and recent results have greatly strengthened this hypothesis. Narcolepsy with hcrt deficiency is now known to be associated with a Huma...

  6. 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.

  7. Gastric emptying in patients with vitamin B12 deficiency

    International Nuclear Information System (INIS)

    Yagci, Muenci; Yamac, Kadri; Acar, Kadir; Haznedar, Rauf; Cingi, Elif; Kitapci, Mehmet

    2002-01-01

    The clinical presentation of patients with vitamin B 12 deficiency varies in a spectrum ranging from haematological disorders to neuropsychiatric diseases. In rare cases, orthostatic hypotension, impotence, constipation and urinary retention have been attributed to autonomic nervous system dysfunction due to vitamin B 12 deficiency. The aim of this study was to evaluate the effect of vitamin B 12 deficiency on autonomic nervous system function by studying gastric emptying times (T 1/2 ). Twenty patients with newly diagnosed vitamin B 12 deficiency and 12 control patients with gastritis and normal vitamin B 12 levels were enrolled in this study. Gastroduodenoscopy, endoscopic biopsy, histopathological evaluation of the biopsy specimens and radionuclide gastric emptying studies were performed. After vitamin B 12 replacement therapy for 3 months, radionuclide gastric emptying studies were repeated. Mean gastric emptying T 1/2 in patients before and after treatment and in controls were 103.83±48.80 min, 90.00±17.29 min and 74.55±8.52 min, respectively. The difference in mean gastric emptying T 1/2 between patients before treatment and controls was statistically significant (P 12 treatment (P 1/2 was somewhat shorter. There were no positive or negative correlations between gastric emptying T 1/2 and the following parameters: haemoglobin, vitamin B 12 level and Helicobacter pylori positivity. In conclusion, gastric emptying T 1/2 was prolonged in patients with vitamin B 12 deficiency and this prolongation was not corrected after vitamin B 12 replacement therapy. Although autonomic nervous system dysfunction due to vitamin B 12 deficiency rarely gives rise to clinical manifestations, latent dysfunction demonstrated by laboratory tests seems to be a frequent phenomenon. The level of vitamin B 12 does not correlate with the degree of autonomic nervous system dysfunction measured by radionuclide gastric emptying studies. (orig.)

  8. Vitamin D deficiency is associated with impaired disease control in asthma–COPD overlap syndrome patients

    Directory of Open Access Journals (Sweden)

    Odler B

    2015-09-01

    Full Text Available Balázs Odler,1 István Ivancsó,1 Vivien Somogyi,1 Kálmán Benke,2 Lilla Tamási,1 Gabriella Gálffy,1 Balázs Szalay,3 Veronika Müller11Department of Pulmonology, 2Heart and Vascular Centre, 3Department of Laboratory Medicine, Semmelweis University, Budapest, HungaryIntroduction: The association between vitamin D and clinical parameters in obstructive lung diseases (OLDs, including COPD and bronchial asthma, was previously investigated. As asthma–COPD overlap syndrome (ACOS is a new clinical entity, the prevalence of vitamin D levels in ACOS is unknown.Aim: Our aim was to assess the levels of circulating vitamin D (25-hydroxyvitamin D [25(OHD] in different OLDs, including ACOS patients, and its correlation with clinical parameters.Methods: A total of 106 men and women (control, n=21; asthma, n=44; COPD, n=21; and ACOS, n=20 were involved in the study. All patients underwent detailed clinical examinations; disease control and severity was assessed by disease-specific questionnaires (COPD assessment test, asthma control test, and modified Medical Research Council; furthermore, 25(OHD levels were measured in all patients.Results: The 25(OHD level was significantly lower in ACOS and COPD groups compared to asthma group (16.86±1.79 ng/mL and 14.27±1.88 ng/mL vs 25.66±1.91 ng/mL. A positive correlation was found between 25(OHD level and forced expiratory volume in 1 second (r=0.4433; P<0.0001, forced vital capacity (FVC (r=0.3741; P=0.0004, forced expiratory flow between 25% and 75% of FVC (r=0.4179; P<0.0001, and peak expiratory flow (r=0.4846; P<0.0001 in OLD patient groups. Asthma control test total scores and the 25(OHD level showed a positive correlation in the ACOS (r=0.4761; P=0.0339 but not in the asthma group. Higher COPD assessment test total scores correlated with decreased 25(OHD in ACOS (r=-0.4446; P=0.0495; however, this was not observed in the COPD group.Conclusion: Vitamin D deficiency is present in ACOS patients and

  9. Estudo de prevalência em recém-nascidos por deficiência de biotinidase Neonatal screening for biotinidase deficiency

    Directory of Open Access Journals (Sweden)

    Anna L. R. Pinto

    1998-04-01

    casos afetados, com sensibilidade de 100% e especificidade de 99,88%. A relação custo/benefício foi satisfatória, permitindo a inclusão do teste de detecção de deficiência de biotinidase no programa de triagem neonatal do Estado do Paraná.INTRODUCTION: Biotinidase deficiency is an inheritable disorder of biotin metabolism. This disorder fulfills major criteria for consideration for newborn screening: the affected children do not show clinical signs in the newborn period; the disease is highly disabling; treatment is effective in preventing neurological sequelae if undertaken promptly. MATERIAL AND METHODS: Screening of 125,000 infants born in Paraná State was carried out to establish the prevalence of biotinidase deficiency. A simple colorimetric procedure was used to detect two infants with biotinidase deficiency (1:62,500, one of them with profound deficiency (1:125,000 and the other with partial deficiency (1:125,000 of the enzyme. RESULTS: There were no known false-negative test results and 0.12% were false-positive, defined by further blood samples which were negative upon repeated testing. Sensitivity was 100% and specificity was 99.88%. Repeat blood samples could not be obtained in 63 (30% suspected cases. CONCLUSIONS: Newborn screening for biotinidase is useful in identifying affected children, is inexpensive and allows early intervention, which may prevent irreversible neurological damage.

  10. Vitamin D deficiency among the elderly: insights from Qatar.

    Science.gov (United States)

    Alhamad, Hanadi Khamis; Nadukkandiyil, Navas; El-Menyar, Ayman; Abdel Wahab, Luay; Sankaranarayanan, Anoop; Al Sulaiti, Essa Mubarak

    2014-06-01

    Vitamin D (VitD) deficiency is associated with comorbidities in the elderly. The present study investigates the prevalence of VitD deficiency among the elderly in Qatar. A retrospective study conducted between April 2010 and April 2012 that involved chart reviews. All elderly patients of age ≥65 years in geriatrics facilities including Rumailah hospital, skilled nursing facility and home healthcare services in Qatar were included in the study. Patient characteristics and outcomes were analyzed and compared according to the severity of VitD deficiency. Correlation of VitD with comorbidities was analyzed. Mean follow-up period was 6 months. A total of 889 patients were enrolled; the majority (66%) were females and the mean age was 75 ± 8.7 years. Patient comorbidities included hypertension (76.5%), diabetes mellitus (63%), dyslipidemia, (47.5%), dementia (26%) coronary artery disease (24%) and cerebrovascular accident (24%). The mean baseline serum VitD level was 24.4 ± 13.5 ng/ml; 72% of patients had VitD deficiency: mild (31%), moderate (30%) and severe (11%). Patients with severe VitD deficiency had significantly higher HbA1c levels compared with patients with optimal VitD (P = 0.03). High density lipoprotein (HDL-C) levels were significantly lower in severe VitD deficiency patients compared with optimal VitD patients (P = 0.04). There was a positive correlation between HDL-C and VitD level (r = 0.17, P = 0.001), whereas HbA1c levels showed negative correlation with VitD (r = -0.15, P = 0.009). A high prevalence of VitD deficiency (72%) was observed among the elderly in Qatar. Lower VitD was associated with higher HbA1c and lower HDL-C levels. Further studies are warranted to evaluate whether VitD supplementation controls diabetes mellitus (DM) and low HDL-C levels among the elderly.

  11. Disease: H01983 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available ia. CACT deficiency is clinically characterized by life-threatening non-ketotic hypoglycemia and rhabdomyo...lysis. Inherited metabolic disease; Mitochondrial disease SLC25A20 [HSA:788] [KO:K1

  12. Possible association between vitamin D deficiency and restless legs syndrome

    Directory of Open Access Journals (Sweden)

    Oran M

    2014-05-01

    Full Text Available Mustafa Oran,1 Cuneyt Unsal,2 Yakup Albayrak,2 Feti Tulubas,3 Keriman Oguz,4 Okan Avci,1 Nilda Turgut,4 Recep Alp,4 Ahmet Gurel3 1Department of Internal Medicine, 2Department of Psychiatry, 3Department of Biochemistry, 4Department of Neurology, Namik Kemal University, Faculty of Medicine, Tekirdağ, Turkey Background and aim: Restless legs syndrome (RLS is a distressing sleep disorder that occurs worldwide. Although there have been recent developments in understanding the pathophysiology of RLS, the exact mechanism of the disease has not been well elucidated. An increased prevalence of neurologic and psychiatric diseases involving dopaminergic dysfunction in vitamin D-deficient patients led us to hypothesize that vitamin D deficiency might result in dopaminergic dysfunction and consequently, the development of RLS (in which dopaminergic dysfunction plays a pivotal role. Thus, the aim of this study was to evaluate the relationship between vitamin D deficiency and RLS. Methods: One hundred and fifty-five consecutive patients, 18–65 years of age, who were admitted to the Department of Internal Medicine with musculoskeletal symptoms and who subsequently underwent neurological and electromyography (EMG examination by the same senior neurologist, were included in this study. The patients were divided into two groups according to serum 25-hydroxyvitamin D (25(OHD (a vitamin D metabolite used as a measure of vitamin D status level: 36 patients with serum 25(OHD levels ≥20 ng/mL comprised the normal vitamin D group, and 119 patients with serum 25(OHD levels <20 ng/mL comprised the vitamin D deficiency group. The two groups were compared for the presence of RLS and associated factors. Results: The two groups were similar in terms of mean age, sex, mean body mass index (BMI, and serum levels of calcium, phosphate, alkaline phosphatase (ALP, and ferritin. The presence of RLS was significantly higher in the vitamin D deficiency group (χ2=12.87, P<0

  13. Iron-Deficiency Anemia

    Medline Plus

    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 ...

  14. Iron-Deficiency Anemia

    Medline Plus

    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 ...

  15. Iron-Deficiency Anemia

    Medline Plus

    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. ...

  16. Iron-Deficiency Anemia

    Medline Plus

    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. ...

  17. Iron-Deficiency Anemia

    Medline Plus

    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 ...

  18. Iron-Deficiency Anemia

    Medline Plus

    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. ...

  19. Iron-Deficiency Anemia

    Medline Plus

    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 ...

  20. Iron-Deficiency Anemia

    Medline Plus

    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 ...

  1. Iron-Deficiency Anemia

    Medline Plus

    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 . ...

  2. Iron-Deficiency Anemia

    Medline Plus

    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 ...

  3. Clear correlation of genotype with disease phenotype in very-long-chain acyl-CoA dehydrogenase deficiency

    DEFF Research Database (Denmark)

    Andresen, B S; Olpin, S; Poorthuis, B J

    1999-01-01

    Very-long-chain acyl-CoA dehydrogenase (VLCAD) catalyzes the initial rate-limiting step in mitochondrial fatty acid beta-oxidation. VLCAD deficiency is clinically heterogenous, with three major phenotypes: a severe childhood form, with early onset, high mortality, and high incidence of cardiomyop......Very-long-chain acyl-CoA dehydrogenase (VLCAD) catalyzes the initial rate-limiting step in mitochondrial fatty acid beta-oxidation. VLCAD deficiency is clinically heterogenous, with three major phenotypes: a severe childhood form, with early onset, high mortality, and high incidence...... of cardiomyopathy; a milder childhood form, with later onset, usually with hypoketotic hypoglycemia as the main presenting feature, low mortality, and rare cardiomyopathy; and an adult form, with isolated skeletal muscle involvement, rhabdomyolysis, and myoglobinuria, usually triggered by exercise or fasting......-phenotype relationship is in sharp contrast to what has been observed in medium-chain acyl-CoA dehydrogenase deficiency, in which no correlation between genotype and phenotype can be established....

  4. Vitamin E deficiency depressed fish growth, disease resistance, and the immunity and structural integrity of immune organs in grass carp (Ctenopharyngodon idella): Referring to NF-κB, TOR and Nrf2 signaling.

    Science.gov (United States)

    Pan, Jia-Hong; Feng, Lin; Jiang, Wei-Dan; Wu, Pei; Kuang, Sheng-Yao; Tang, Ling; Zhang, Yong-An; Zhou, Xiao-Qiu; Liu, Yang

    2017-01-01

    This study investigated the effects of dietary vitamin E on growth, disease resistance and the immunity and structural integrity of head kidney, spleen and skin in grass carp (Ctenopharyngodon idella). The fish were fed six diets containing graded levels of vitamin E (0, 45, 90, 135, 180 and 225 mg/kg diet) for 10 weeks. Subsequently, a challenge test was conducted by injection of Aeromonas hydrophila. The results showed that compared with optimal vitamin E supplementation, vitamin E deficiency caused depressed growth, poor survival rates and increased skin lesion morbidity in grass carp. Meanwhile, vitamin E deficiency decreased lysozyme and acid phosphatase activities, complement component 3 and complement component 4 contents in the head kidney, spleen and skin of grass carp (P vitamin E deficiency down-regulated antimicrobial peptides (Hepcidin, liver-expressed antimicrobial peptide-2A, -2B, β-defensin), IL-10, TGFβ1, IκBα, TOR and S6K1 mRNA levels (P vitamin E deficiency caused oxidative damage, decreased superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT) and glutathione reductase (GR) activities, and down-regulated the mRNA levels of antioxidant enzymes and signaling molecules Nrf2 (P Vitamin E deficiency also induced apoptosis by up-regulating capase-2, -3, -7, and -8 mRNA levels in the head kidney, spleen and skin of grass carp. In conclusion, this study indicated that dietary vitamin E deficiency depressed fish growth, impaired the immune function and disturbed the structural integrity of the head kidney, spleen and skin in grass carp, but optimal vitamin E supplementation can reverse those negative effects in fish. The optimal vitamin E requirements for young grass carp (266.39-1026.63 g) to achieve optimal growth performance and disease resistance based on the percent weight gain (PWG) and skin lesion morbidity were estimated to be 116.2 and 130.9 mg/kg diet, respectively. Meanwhile, based on immune indicator (LA activity

  5. Mitochondrial oxodicarboxylate carrier deficiency is associated with mitochondrial DNA depletion and spinal muscular atrophy-like disease.

    Science.gov (United States)

    Boczonadi, Veronika; King, Martin S; Smith, Anthony C; Olahova, Monika; Bansagi, Boglarka; Roos, Andreas; Eyassu, Filmon; Borchers, Christoph; Ramesh, Venkateswaran; Lochmüller, Hanns; Polvikoski, Tuomo; Whittaker, Roger G; Pyle, Angela; Griffin, Helen; Taylor, Robert W; Chinnery, Patrick F; Robinson, Alan J; Kunji, Edmund R S; Horvath, Rita

    2018-03-08

    PurposeTo understand the role of the mitochondrial oxodicarboxylate carrier (SLC25A21) in the development of spinal muscular atrophy-like disease.MethodsWe identified a novel pathogenic variant in a patient by whole-exome sequencing. The pathogenicity of the mutation was studied by transport assays, computer modeling, followed by targeted metabolic testing and in vitro studies in human fibroblasts and neurons.ResultsThe patient carries a homozygous pathogenic variant c.695A>G; p.(Lys232Arg) in the SLC25A21 gene, encoding the mitochondrial oxodicarboxylate carrier, and developed spinal muscular atrophy and mitochondrial myopathy. Transport assays show that the mutation renders SLC25A21 dysfunctional and 2-oxoadipate cannot be imported into the mitochondrial matrix. Computer models of central metabolism predicted that impaired transport of oxodicarboxylate disrupts the pathways of lysine and tryptophan degradation, and causes accumulation of 2-oxoadipate, pipecolic acid, and quinolinic acid, which was confirmed in the patient's urine by targeted metabolomics. Exposure to 2-oxoadipate and quinolinic acid decreased the level of mitochondrial complexes in neuronal cells (SH-SY5Y) and induced apoptosis.ConclusionMitochondrial oxodicarboxylate carrier deficiency leads to mitochondrial dysfunction and the accumulation of oxoadipate and quinolinic acid, which in turn cause toxicity in spinal motor neurons leading to spinal muscular atrophy-like disease.GENETICS in MEDICINE advance online publication, 8 March 2018; doi:10.1038/gim.2017.251.

  6. 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 ...

  7. Effect of late-stage therapy on disease progression in AAV-mediated rescue of photoreceptor cells in the retinoschisin-deficient mouse.

    Science.gov (United States)

    Janssen, Andreas; Min, Seok H; Molday, Laurie L; Tanimoto, Naoyuki; Seeliger, Mathias W; Hauswirth, William W; Molday, Robert S; Weber, Bernhard H F

    2008-06-01

    Proof-of-concept for a successful adeno-associated virus serotype 5 (AAV5)-mediated gene therapy in X-linked juvenile retinoschisis (XLRS) has been demonstrated in an established mouse model for this condition. The initial studies concentrated on early time-points of treatment. In this study, we aimed to explore the consequences of single subretinal injections administered at various stages of more advanced disease. By electroretinogram (ERG), functional improvement in treated versus untreated eyes is found to be significant in retinoschisin-deficient mice injected at the time-points of 15 days (P15), 1 month (PM1), and 2 months (PM2) after birth. In mice treated at 7 months after birth (PM7), an age previously shown to exhibit advanced retinal disease, ERG responses reveal no beneficial effects of vector treatment. Generally, functional rescue is paralleled by sustained retinoschisin expression and significant photoreceptor survival relative to untreated eyes. Quantitative measures of photoreceptors and peanut agglutinin-labeled ribbon synapses demonstrate rescue effects even in mice injected as late as PM7. Taken together, AAV5-mediated gene replacement is beneficial in slowing disease progression in murine XLRS. In addition, we show the effectiveness of rescue efforts even if treatment is delayed until advanced signs of disease have developed. Human XLRS patients might benefit from these findings, which suggest that the effectiveness of treatment appears not to be restricted to the early stages of the disease, and that treatment may prove to be valuable even when administered at more advanced stages.

  8. [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

  9. 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 ...

  10. 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 ...

  11. Iron-Deficiency Anemia

    Medline Plus

    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 ...

  12. Iron deficiency anaemia -a risk factor for febrile seizures in children

    International Nuclear Information System (INIS)

    Sherjil, A.; Saeed, Z.U.; Shehzad, S.; Amjad, R.

    2010-01-01

    Background: Iron deficiency anaemia and febrile seizures are two common diseases in children worldwide as well as in our country. Iron insufficiency is known to cause neurological symptoms like behavioural changes, poor attention span and learning deficits in children. Therefore, it may also be associated with other neurological disturbances like febrile seizures in children. Objective of our case-control study was to find association between iron deficiency anaemia and febrile seizures in children. Methods: This multicentre study was conducted in Department of Paediatrics HIT Hospital Taxila Cantt, Department of Paediatrics CMH Mangla and Department of Paediatrics POF Hospital Wah Cantt, from June 2008 to June 2010. Three hundred and ten children aged between 6 months to 6 years were included in the study. One hundred and fifty-seven children who presented with febrile seizures were our cases, while, 153 children who presented with febrile illnesses without seizures were recruited as controls. All patients were assessed for iron deficiency anaemia by measuring haemoglobin level, serum ferritin level, Mean Corpuscular Haemoglobin Concentration (MCHC) and Mean Corpuscular Volume (MCV). Patients with iron deficiency anaemia amongst controls and cases were documented. Percentages and Odds ratio were derived from the collected data. Results: 31.85% of cases (50 out of 157) had iron deficiency anaemia whereas, 19.6% of controls (30 out of 153) were found to have iron deficiency anaemia as revealed by low levels of haemoglobin level, serum ferritin level, Mean Corpuscular Haemoglobin Concentration and Mean Corpuscular Volume. Odds ratio was 1.93. Conclusion: Patients with febrile seizures are 1.93 times more likely to have iron deficiency anaemia compared to febrile patients without seizures. (author)

  13. Intravenous immunoglobulin to treat hyperbilirubinemia in neonates with isolated Glucose-6-Phosphate dehydrogenase deficiency

    Directory of Open Access Journals (Sweden)

    Wadah Khriesat

    2017-04-01

    Full Text Available Background Glucose-6-phosphate dehydrogenase deficiency alone or concomitant with ABO isoimmunisation is a widespread indication for neonatal exchange transfusion. Aims To evaluate the effectiveness of Intravenous Immunoglobulin in the treatment of neonatal hyperbilirubinemia due to glucose-6-phosphate dehydrogenase deficiency. Methods A retrospective cohort study was conducted between 2006 and 2014 at the Jordan University of Science and technology. The medical records of 43 infants admitted to the neonatal intensive care unit for isolated glucose-6- phosphate dehydrogenase deficiency hemolytic disease of the newborns were reviewed. Patients were divided into two groups. Group I, a historical cohort, included newborns born between 2006 and 2010, Treatment included phototherapy and exchange transfusion. Group II included newborns born between 2011 and 2014, where, in addition to phototherapy, intravenous immunoglobulin was administered. The duration of phototherapy and number of exchange transfusions were evaluated. Results Of 412 newborns that were admitted with neonatal hyperbilirubinemia, Glucose-6-phosphate dehydrogenase deficiency was present in 43. Of these, 22, did not receive intravenous immunoglobulin and served as a control group. The other 21 newborns received intravenous immunoglobulin. There was no difference in the demographic characteristics between the two groups. Infants in the control group were significantly more likely to receive exchange blood transfusion than infants in the immunoglobulin treatment group, but were significantly less likely to need phototherapy. Conclusion Intravenous immunoglobulin is an effective alternative to exchange transfusion in infants with glucose-6-phosphate dehydrogenase deficiency hemolytic disease of the newborn. It is suggested that intravenous immunoglobulin may be beneficial as a prophylaxis for infants with hyperbilirubinemia.

  14. 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 ...

  15. 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 ...

  16. Iron-Deficiency Anemia

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    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 ...

  17. 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 ...

  18. 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. ...

  19. 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 ...

  20. Peripheral neuropathy in a copper-deficient goat

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    Valdir Morais de Almeida

    2017-09-01

    Full Text Available ABSTRACT: This report aimed to describe a case of peripheral neuropathy in a copper-deficient goat, and highlights the clinical, and pathological features of the disease. The goat had low body score, hyporexia, alopecia, achromotrichia, left hindlimb protraction, paralysis with dragging of digit and difficulty to stand up and microcytic normochromic anemia. Copper concentration in serum was markedly lower (2.0µmol L-1 whereas the iron serum content was significantly increased (51.0µmol L-1. The main gross alteration was the reduction of the quadriceps vastus laterallis muscle volume. Histologically, there was atrophy of the quadriceps vastus laterallis muscle and presence of satellite cells, infiltration of lymphocytes, macrophages and replacement of the fibers by connective tissue. In the femoral nerve, there was axonal degeneration with myelin sheath expansion and presence of vacuoles, usually in chains and containing axonal debris or macrophages. Clinical, laboratorial and pathologic findings are consistent with peripheral neuropathy due to a severy copper deficiency.