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Sample records for combined respiratory-chain deficiency

  1. HIBCH mutations can cause Leigh-like disease with combined deficiency of multiple mitochondrial respiratory chain enzymes and pyruvate dehydrogenase

    NARCIS (Netherlands)

    Ferdinandusse, Sacha; Waterham, Hans R.; Heales, Simon J. R.; Brown, Garry K.; Hargreaves, Iain P.; Taanman, Jan-Willem; Gunny, Roxana; Abulhoul, Lara; Wanders, Ronald J. A.; Clayton, Peter T.; Leonard, James V.; Rahman, Shamima

    2013-01-01

    Deficiency of 3-hydroxy-isobutyryl-CoA hydrolase (HIBCH) caused by HIBCH mutations is a rare cerebral organic aciduria caused by disturbance of valine catabolism. Multiple mitochondrial respiratory chain (RC) enzyme deficiencies can arise from a number of mechanisms, including defective maintenance

  2. Fumarate Hydratase Loss Causes Combined Respiratory Chain Defects

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    Petros A. Tyrakis

    2017-10-01

    Full Text Available Fumarate hydratase (FH is an enzyme of the tricarboxylic acid (TCA cycle mutated in hereditary and sporadic cancers. Despite recent advances in understanding its role in tumorigenesis, the effects of FH loss on mitochondrial metabolism are still unclear. Here, we used mouse and human cell lines to assess mitochondrial function of FH-deficient cells. We found that human and mouse FH-deficient cells exhibit decreased respiration, accompanied by a varying degree of dysfunction of respiratory chain (RC complex I and II. Moreover, we show that fumarate induces succination of key components of the iron-sulfur cluster biogenesis family of proteins, leading to defects in the biogenesis of iron-sulfur clusters that affect complex I function. We also demonstrate that suppression of complex II activity is caused by product inhibition due to fumarate accumulation. Overall, our work provides evidence that the loss of a single TCA cycle enzyme is sufficient to cause combined RC activity dysfunction.

  3. Adult, isolated respiratory chain complex IV deficiency with minimal manifestations.

    Science.gov (United States)

    Finsterer, Josef; Kovacs, Gabor G; Rauschka, Helmut; Ahting, Uwe

    2015-01-01

    Isolated complex IV (cytochrome c oxidase) deficiency is one of the most frequent respiratory chain defects in mitochondrial disorders (MIDs) and usually occurs together with severe pediatric or rarely adult multisystem disease. Here we report an adult with isolated complex IV deficiency with unusually mild clinical manifestations. A 50-year-old man had developed generalized muscle aches and occasional twitching and stiffness of the musculature since age 48 years. He had a previous history of diabetes, acute hearing loss, hyperlipidemia, hyperuricemia, arterial hypertension, polyarthrosis, hypogonadism, and hypothyroidism. The family history was positive for diabetes (mother), CK elevation (brother), myalgias (brother), and proximal weakness of the upper limbs (mother). Work-up revealed hypoacusis, postural tremor and reduced tendon reflexes, recurrent mild hyper-CK-emia, neurogenic needle electromyography, and a muscle biopsy with mild non-specific changes. Biochemical investigations of the muscle homogenate revealed an isolated complex IV defect and reduced amounts of coenzyme Q (CoQ). He profited from CoQ supplementation, low-carbohydrate diet, and gluten-free diet. Isolated complex IV deficiency may present with only mild muscular, endocrine, or cardiac manifestations in adults. Coenzyme Q supplementation, low-carbohydrate diet, and gluten-free diet may have a beneficial effect at least on some of the manifestations.

  4. Cultured human muscle cells and respiratory chain deficiencies

    NARCIS (Netherlands)

    Herzberg, N. H.; Bolhuis, P. A.; van den Bogert, C.; Barth, P. G.

    1994-01-01

    Cultured muscle cells are useful in the study of respiratory chain disorders. Muscle tissue is affected in most cases and muscle biopsies are often taken for diagnostic purposes. Small samples of the biopsies can provide large numbers of muscle cells. In contrast with most other cell types, the

  5. [Aspect of brain MRI in mitochondrial respiratory chain deficiency. A diagnostic algorithm of the most common mitochondrial genetic mutations].

    Science.gov (United States)

    Devaux-Bricout, M; Grévent, D; Lebre, A-S; Rio, M; Desguerre, I; De Lonlay, P; Valayannopoulos, V; Brunelle, F; Rötig, A; Munnich, A; Boddaert, N

    2014-05-01

    Mitochondrial diseases are due to deficiency of the respiratory chain and are characterized by a broad clinical and genetic heterogeneity that makes diagnosis difficult. Some clinical presentations are highly suggestive of given gene mutations, allowing rapid genetic diagnosis. However, owing to the wide pattern of symptoms in mitochondrial disorders and the constantly growing number of disease genes, their genetic diagnosis is frequently difficult and genotype/phenotype correlations remain elusive. For this reason, brain MRI appears as a useful tool for genotype/phenotype correlations. Here, we report the most frequent neuroradiological signs in mitochondrial respiratory chain deficiency and we propose a diagnostic algorithm based on neuroimaging features, so as to direct molecular genetic tests in patients at risk of mitochondrial respiratory chain deficiency. This algorithm is based on the careful analysis of five areas on brain MRI: (1) basal ganglia (hyperintensities on T2 or calcifications); (2) cerebellum (hyperintensities on T2 or atrophy); (3) brainstem (hyperintensities on T2 or atrophy); (4) white matter (leukoencephalopathy); (5) cortex (sub-tentorial atrophy); (6) stroke-like episodes. We believe that the combination of brain MRI features is of value to support respiratory chain deficiency and direct molecular genetic tests. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  6. A Comprehensive Genomic Analysis Reveals the Genetic Landscape of Mitochondrial Respiratory Chain Complex Deficiencies.

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    Masakazu Kohda

    2016-01-01

    Full Text Available Mitochondrial disorders have the highest incidence among congenital metabolic disorders characterized by biochemical respiratory chain complex deficiencies. It occurs at a rate of 1 in 5,000 births, and has phenotypic and genetic heterogeneity. Mutations in about 1,500 nuclear encoded mitochondrial proteins may cause mitochondrial dysfunction of energy production and mitochondrial disorders. More than 250 genes that cause mitochondrial disorders have been reported to date. However exact genetic diagnosis for patients still remained largely unknown. To reveal this heterogeneity, we performed comprehensive genomic analyses for 142 patients with childhood-onset mitochondrial respiratory chain complex deficiencies. The approach includes whole mtDNA and exome analyses using high-throughput sequencing, and chromosomal aberration analyses using high-density oligonucleotide arrays. We identified 37 novel mutations in known mitochondrial disease genes and 3 mitochondria-related genes (MRPS23, QRSL1, and PNPLA4 as novel causative genes. We also identified 2 genes known to cause monogenic diseases (MECP2 and TNNI3 and 3 chromosomal aberrations (6q24.3-q25.1, 17p12, and 22q11.21 as causes in this cohort. Our approaches enhance the ability to identify pathogenic gene mutations in patients with biochemically defined mitochondrial respiratory chain complex deficiencies in clinical settings. They also underscore clinical and genetic heterogeneity and will improve patient care of this complex disorder.

  7. Respiratory chain complex I deficiency due to NDUFA12 mutations as a new cause of Leigh syndrome

    DEFF Research Database (Denmark)

    Ostergaard, Elsebet; Rodenburg, Richard J; van den Brand, Mariël

    2011-01-01

    This study investigated a girl with Leigh syndrome born to first-cousin parents of Pakistani descent with an isolated respiratory chain complex I deficiency in muscle and fibroblasts. Her early development was delayed, and from age 2 years she started losing motor abilities. Cerebral MRI showed b...

  8. Mitochondrial respiratory chain deficiency in Caenorhabditis elegans results in developmental arrest and increased life span.

    Science.gov (United States)

    Tsang, W Y; Sayles, L C; Grad, L I; Pilgrim, D B; Lemire, B D

    2001-08-24

    The growth and development of Caenorhabditis elegans are energy-dependent and rely on the mitochondrial respiratory chain (MRC) as the major source of ATP. The MRC is composed of approximately 70 nuclear and 12 mitochondrial gene products. Complexes I and V are multisubunit proteins of the MRC. The nuo-1 gene encodes the NADH- and FMN-binding subunit of complex I, the NADH-ubiquinone oxidoreductase. The atp-2 gene encodes the active-site subunit of complex V, the ATP synthase. The nuo-1(ua1) and atp-2(ua2) mutations are both lethal. They result in developmental arrest at the third larval stage (L3), arrest of gonad development at the second larval stage (L2), and impaired mobility, pharyngeal pumping, and defecation. Surprisingly, the nuo-1 and atp-2 mutations significantly lengthen the life spans of the arrested animals. When MRC biogenesis is blocked by chloramphenicol or doxycycline (inhibitors of mitochondrial translation), a quantitative and homogeneous developmental arrest as L3 larvae also results. The common phenotype induced by the mutations and drugs suggests that the L3-to-L4 transition may involve an energy-sensing developmental checkpoint. Since approximately 200 gene products are needed for MRC assembly and mtDNA replication, transcription, and translation, we predict that L3 arrest will be characteristic of mutations in these genes.

  9. The mitochondrial DNA mutation ND6*14,484C associated with leber hereditary optic neuropathy, leads to deficiency of complex I of the respiratory chain

    NARCIS (Netherlands)

    Oostra, R. J.; van Galen, M. J.; Bolhuis, P. A.; Bleeker-Wagemakers, E. M.; van den Bogert, C.

    1995-01-01

    The electron transfer activity of Complex I of the respiratory chain and Complex I-linked ATP synthesis were investigated in leukocytes of four males affected by Leber hereditary optic neuropathy and a mutation in the ND6 gene at nucleotide position 14,484 of mtDNA. The electron transfer activity in

  10. Mitochondrial respiratory chain disorders in the Old Order Amish population.

    Science.gov (United States)

    Ghaloul-Gonzalez, Lina; Goldstein, Amy; Walsh Vockley, Catherine; Dobrowolski, Steven F; Biery, Amy; Irani, Afifa; Ibarra, Jordan; Morton, D Holmes; Mohsen, Al-Walid; Vockley, Jerry

    2016-08-01

    The Old Order Amish populations in the US are one of the Plain People groups and are descendants of the Swiss Anabaptist immigrants who came to North America in the early eighteenth century. They live in numerous small endogamous demes that have resulted in reduced genetic diversity along with a high prevalence of specific genetic disorders, many of them autosomal recessive. Mitochondrial respiratory chain deficiencies arising from mitochondrial or nuclear DNA mutations have not previously been reported in the Plain populations. Here we present four different Amish families with mitochondrial respiratory chain disorders. Mutations in two mitochondrial encoded genes leading to mitochondrial respiratory chain disorder were identified in two patients. In the first case, MELAS syndrome caused by a mitochondrial DNA (mtDNA) mutation (m.3243A>G) was identified in an extended Amish pedigree following a presentation of metabolic strokes in the proband. Characterization of the extended family of the proband by a high resolution melting assay identified the same mutation in many previously undiagnosed family members with a wide range of clinical symptoms. A MELAS/Leigh syndrome phenotype caused by a mtDNA mutation [m.13513G>A; p.Asp393Asn] in the ND5 gene encoding the ND5 subunit of respiratory chain complex I was identified in a patient in a second family. Mutations in two nuclear encoded genes leading to mitochondrial respiratory chain disorder were also identified in two patients. One patient presented with Leigh syndrome and had a homozygous deletion in the NDUFAF2 gene, while the second patient had a homozygous mutation in the POLG gene, [c.1399G>A; p.Ala467Thr]. Our findings identify mitochondrial respiratory chain deficiency as a cause of disease in the Old Order Amish that must be considered in the context of otherwise unexplained systemic disease, especially if neuromuscular symptoms are present. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Defect of mitochondrial respiratory chain is a mechanism of ROS overproduction in a rat model of alcoholic liver disease: role of zinc deficiency.

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    Sun, Qian; Zhong, Wei; Zhang, Wenliang; Zhou, Zhanxiang

    2016-02-01

    Morphological and functional alterations of hepatic mitochondria have been documented in patients with alcoholic liver disease (ALD). Our recent study demonstrated that zinc level was decreased in whole liver and mitochondria by chronic alcohol feeding. The present study was undertaken to determine whether zinc deficiency mediates alcohol-induced mitochondrial electron transport chain (ETC) defect and whether defective ETC function may lead to generation of reactive oxygen species (ROS). Male Wistar rats were pair fed with the Lieber-DeCarli control or ethanol diet for 5 mo. Chronic alcohol exposure increased hepatic triglyceride, free fatty acid, and 4-hydroxynonenal (4HNE) levels; meanwhile hepatic mitochondrial 4HNE level was also increased. Moreover, hepatic mitochondrial respiratory complexes I, III, IV, and V and hepatic ATP production were decreased by chronic alcohol exposure. Chronic alcohol feeding decreased peroxisome proliferator-activated receptor gamma coactivator-1-alpha (PGC1α), nuclear respiratory factor 1 (NRF1), mitochondrial transcription factor A (TFAM), and mitochondrial DNA. HepG2 cells were treated with N,N,N',N'-tetrakis (2-pyridylmethyl) ethylenediamine (TPEN) for 6 h. Zinc deficiency significantly decreased mitochondrial respiratory complexes I, III, and IV. In addition, PGC1α, NRF1, and TFAM levels as well as mitochondrial DNA were significantly decreased by TPEN treatment. Knockdown of mitochondrial respiratory complexes I, III, or IV by shRNA caused a decrease in mitochondrial membrane potential and an increase in ROS production. These results suggest that alcohol-induced hepatic zinc deficiency could inactivate mitochondrial biogenesis pathway and decrease mitochondrial DNA replication, which, in turn, decreases mitochondrial complex protein expression. The defect of mitochondrial respiratory complexes may worsen alcohol-induced ROS production. Copyright © 2016 the American Physiological Society.

  12. The Respiratory Chain of Alkaliphilic Bacteria

    Energy Technology Data Exchange (ETDEWEB)

    Terry Ann Krulwich

    2008-01-29

    Alkaliphilic bacteria that grow at extremely high pH are confronted by particular bioenergetic problems in carrying out oxidative phosphorylation. This project focused on the properties and adaptations of the respiratory chain. The respiratory chain as a whole, the redox poises of its components and several individual complexes of the respiratory chain of alkaliphilic Bacillus pseudofirmus OF4 have been characterized as part of this project and, importantly, this project has helped support the development of genetic tools that make B. pseudofirmus OF4 the most genetically tractable and, hence, most bioenergetically characterized extreme alkaliphile. Evidence has been obtained for a pivotal role of the cca3-type terminal oxidase in oxidative phosphorylation, especially at high pH and motifs that may be relevant to that special role have been identified.

  13. Liver transplantation in mitochondrial respiratory chain disorders

    NARCIS (Netherlands)

    Sokal, EM; Sokol, R; Cormier, [No Value; Lacaille, F; McKiernan, P; Van Spronsen, FJ; Bernard, O; Saudubray, JM

    1999-01-01

    Mitochondrial respiratory chain disease may lead to neonatal or late onset liver failure, requiring liver transplantation. In rare cases, the disease is restricted to the liver and the patient is cured after surgery. More frequently, other organs are simultaneously involved and neuromuscular or

  14. Extensive respiratory chain defects in inhibitory interneurones in patients with mitochondrial disease.

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    Lax, Nichola Z; Grady, John; Laude, Alex; Chan, Felix; Hepplewhite, Philippa D; Gorman, Grainne; Whittaker, Roger G; Ng, Yi; Cunningham, Mark O; Turnbull, Doug M

    2016-02-01

    Mitochondrial disorders are among the most frequently inherited cause of neurological disease and arise due to mutations in mitochondrial or nuclear DNA. Currently, we do not understand the specific involvement of certain brain regions or selective neuronal vulnerability in mitochondrial disease. Recent studies suggest γ-aminobutyric acid (GABA)-ergic interneurones are particularly susceptible to respiratory chain dysfunction. In this neuropathological study, we assess the impact of mitochondrial DNA defects on inhibitory interneurones in patients with mitochondrial disease. Histochemical, immunohistochemical and immunofluorescent assays were performed on post-mortem brain tissue from 10 patients and 10 age-matched control individuals. We applied a quantitative immunofluorescent method to interrogate complex I and IV protein expression in mitochondria within GABAergic interneurone populations in the frontal, temporal and occipital cortices. We also evaluated the density of inhibitory interneurones in serial sections to determine if cell loss was occurring. We observed significant, global reductions in complex I expression within GABAergic interneurones in frontal, temporal and occipital cortices in the majority of patients. While complex IV expression is more variable, there is reduced expression in patients harbouring m.8344A>G point mutations and POLG mutations. In addition to the severe respiratory chain deficiencies observed in remaining interneurones, quantification of GABAergic cell density showed a dramatic reduction in cell density suggesting interneurone loss. We propose that the combined loss of interneurones and severe respiratory deficiency in remaining interneurones contributes to impaired neuronal network oscillations and could underlie development of neurological deficits, such as cognitive impairment and epilepsy, in mitochondrial disease. © 2015 The Authors. Neuropathology and Applied Neurobiology published by John Wiley & Sons Ltd on behalf of

  15. Molecular mechanisms of superoxide production by the mitochondrial respiratory chain

    NARCIS (Netherlands)

    Drose, S.; Brandt, U.

    2012-01-01

    The mitochondrial respiratory chain is a major source of reactive oxygen species (ROS) in eukaryotic cells. Mitochondrial ROS production associated with a dysfunction of respiratory chain complexes has been implicated in a number of degenerative diseases and biological aging. Recent findings suggest

  16. A rare combination: Combined factor V and factor VIII deficiency

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    Başak Ünver Koluman

    2014-06-01

    Full Text Available Combined factor V (FV and factor VIII (FVIII deficiency is a rare factor deficiency with mild-moderate hemorrhage. It is an autosomal recessive coagulation disorder . Prolonged prothrombin time and partial thromboplastic time is characteristic, platelet count remains in normal ranges. The main stay of treatment is to control the hemorrhage. Fresh frozen plasma, desmopressin, specific FVIII concentrates (plasma- derived or recombinant may be used. Being very rare in the general population, we present a case with a combined FV and FVIII deficiency. J Clin Exp Invest 2014; 5 (2: 323-325

  17. High molecular weight forms of mammalian respiratory chain complex II.

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    Nikola Kovářová

    Full Text Available Mitochondrial respiratory chain is organised into supramolecular structures that can be preserved in mild detergent solubilisates and resolved by native electrophoretic systems. Supercomplexes of respiratory complexes I, III and IV as well as multimeric forms of ATP synthase are well established. However, the involvement of complex II, linking respiratory chain with tricarboxylic acid cycle, in mitochondrial supercomplexes is questionable. Here we show that digitonin-solubilised complex II quantitatively forms high molecular weight structures (CIIhmw that can be resolved by clear native electrophoresis. CIIhmw structures are enzymatically active and differ in electrophoretic mobility between tissues (500 - over 1000 kDa and cultured cells (400-670 kDa. While their formation is unaffected by isolated defects in other respiratory chain complexes, they are destabilised in mtDNA-depleted, rho0 cells. Molecular interactions responsible for the assembly of CIIhmw are rather weak with the complexes being more stable in tissues than in cultured cells. While electrophoretic studies and immunoprecipitation experiments of CIIhmw do not indicate specific interactions with the respiratory chain complexes I, III or IV or enzymes of the tricarboxylic acid cycle, they point out to a specific interaction between CII and ATP synthase.

  18. Mitochondrial respiratory chain disease presenting as progressive bulbar paralysis of childhood

    NARCIS (Netherlands)

    Roeleveld-Versteegh, ABC; Braun, KPJ; Smeitink, JAM; Dorland, L; de Koning, TJ

    2004-01-01

    We report two siblings with a mitochondrial respiratory chain defect who presented with progressive bulbar paralysis of childhood ( Fazio-Londe disease). Mitochondrial respiratory chain defects should be considered in the differential diagnosis of this rare clinical entity.

  19. Mitochondrial respiratory chain disease presenting as progressive bulbar paralysis of childhood.

    NARCIS (Netherlands)

    Roeleveld-Versteegh, A.B.; Braun, K.P.; Smeitink, J.A.M.; Dorland, L.; Koning, T.J.

    2004-01-01

    We report two siblings with a mitochondrial respiratory chain defect who presented with progressive bulbar paralysis of childhood (Fazio-Londe disease). Mitochondrial respiratory chain defects should be considered in differential diagnosis of this rare clinical entity.

  20. Analysis of Escherichia coli mutants with a linear respiratory chain.

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    Sonja Steinsiek

    Full Text Available The respiratory chain of E. coli is branched to allow the cells' flexibility to deal with changing environmental conditions. It consists of the NADH:ubiquinone oxidoreductases NADH dehydrogenase I and II, as well as of three terminal oxidases. They differ with respect to energetic efficiency (proton translocation and their affinity to the different quinone/quinol species and oxygen. In order to analyze the advantages of the branched electron transport chain over a linear one and to assess how usage of the different terminal oxidases determines growth behavior at varying oxygen concentrations, a set of isogenic mutant strains was created, which lack NADH dehydrogenase I as well as two of the terminal oxidases, resulting in strains with a linear respiratory chain. These strains were analyzed in glucose-limited chemostat experiments with defined oxygen supply, adjusting aerobic, anaerobic and different microaerobic conditions. In contrast to the wild-type strain MG1655, the mutant strains produced acetate even under aerobic conditions. Strain TBE032, lacking NADH dehydrogenase I and expressing cytochrome bd-II as sole terminal oxidase, showed the highest acetate formation rate under aerobic conditions. This supports the idea that cytochrome bd-II terminal oxidase is not able to catalyze the efficient oxidation of the quinol pool at higher oxygen conditions, but is functioning mainly under limiting oxygen conditions. Phosphorylation of ArcA, the regulator of the two-component system ArcBA, besides Fnr the main transcription factor for the response towards different oxygen concentrations, was studied. Its phosphorylation pattern was changed in the mutant strains. Dephosphorylation and therefore inactivation of ArcA started at lower aerobiosis levels than in the wild-type strain. Notably, not only the micro- and aerobic metabolism was affected by the mutations, but also the anaerobic metabolism, where the respiratory chain should not be important.

  1. Divergent mitochondrial respiratory chains in phototrophic relatives of apicomplexan parasites

    KAUST Repository

    Flegontov, Pavel

    2015-02-06

    Four respiratory complexes and ATP-synthase represent central functional units in mitochondria. In some mitochondria and derived anaerobic organelles, a few or all of these respiratory complexes have been lost during evolution. We show that the respiratory chain of Chromera velia, a phototrophic relative of parasitic apicomplexans, lacks complexes I and III, making it a uniquely reduced aerobic mitochondrion. In Chromera, putative lactate:cytochrome c oxidoreductases are predicted to transfer electrons from lactate to cytochrome c, rendering complex III unnecessary. The mitochondrial genome of Chromera has the smallest known protein-coding capacity of all mitochondria, encoding just cox1 and cox3 on heterogeneous linear molecules. In contrast, another photosynthetic relative of apicomplexans, Vitrella brassicaformis, retains the same set of genes as apicomplexans and dinoflagellates (cox1, cox3, and cob). © The Author 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  2. Cancer phototherapy via selective photoinactivation of respiratory chain oxidase to trigger a fatal superoxide anion burst.

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    Wu, Shengnan; Zhou, Feifan; Wei, Yanchun; Chen, Wei R; Chen, Qun; Xing, Da

    2014-02-10

    Here, we develop a novel cancer treatment modality using mitochondria-targeting, high-fluence, low-power laser irradiation (HF-LPLI) in mouse tumor models and explore the mechanism of mitochondrial injury by HF-LPLI. We demonstrated that the initial reaction after photon absorption was photosensitization of cytochrome c oxidase (COX), to inhibit enzymatic activity of COX in situ and cause respiratory chain superoxide anion (O2(-•)) burst. We also found that HF-LPLI exerted its main tumor killing effect through mitochondrial O2(-•) burst via electron transport chain (ETC). These phenomena were completely absent in the respiration-deficient cells and COX knockdown cells. With a carefully selected irradiation protocol, HF-LPLI could efficaciously destroy tumors. The inhibition of enzymatic activity of COX and generation of O2(-•) by HF-LPLI in vivo were also detected. It is the first time that the mechanism involved in the interaction between light and its photoacceptor under HF-LPLI treatment is clarified. Our results clearly indicate that HF-LPLI initiates its effects via targeted COX photoinactivation and that the tumor-killing efficacy is dependent of the subsequent mitochondrial O2(-•) burst via ETC. Based on both in vitro and in vivo results, we conclude that HF-LPLI can selectively photoinactivate respiratory chain oxidase to trigger a fatal mitochondrial O2(-•) burst, producing oxidative damage on cancer cells. This study opens up the possibilities of applications of HF-LPLI as a mitochondria-targeting cancer phototherapy.

  3. Mitochondrial Band-7 family proteins: scaffolds for respiratory chain assembly?

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    Bernadette eGehl

    2014-04-01

    Full Text Available The band-7 protein family comprises a diverse set of membrane-bound proteins characterised by the presence of a conserved domain. The exact function of this band-7 domain remains elusive, but examples from animal and bacterial stomatin-type proteins demonstrate binding to lipids and the ability to assemble into membrane-bound oligomers that form putative scaffolds. Some members, such as prohibitins and human stomatin-like protein 2 (HsSLP2, localise to the mitochondrial inner membrane where they function in cristae formation and hyperfusion. In Arabidopsis, the band-7 protein family has diversified and includes plant-specific members. Mitochondrial-localised members include prohibitins (AtPHBs and two stomatin-like proteins (AtSLP1 and -2. Studies into PHB function in plants have demonstrated an involvement in root meristem proliferation and putative scaffold formation for mAAA proteases, but it remains unknown how these roles are achieved at the molecular level. In this minireview we summarise the current status of band-7 protein functions in Arabidopsis, and speculate how the mitochondrial members might recruit specific lipids to form microdomains that could shape the organisation and functioning of the respiratory chain.

  4. [Distribution of endogenous inhibitors of the respiratory chain in plants].

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    Schewe, T; Walther, H; Redmann, T; Rapoport, S

    1975-01-01

    70 phosphate buffer extracts of various plant tissues of 40 species as well as of 2 bacteria were tested for the presence of endogenous inhibitors of the respiratory chain. Electron transfer particles (ETP) from beef heart mitochondria served as test object. The NADH oxidase (spectrophotometrically) and the succinate oxidase activity (manometrically) were measured. Inhibitory activities could be detected in all the plant species tested, but there were quantitative differences by orders of magnitude. The inhibitory effects were more frequent and higher in the NADH oxidase system than those in the succinate oxidase system. The highest inhibitory activities were observed with blossoms of Forsynthia intermedia, male blossoms of Corylus avellana, inflorescences of Brassica oleracea, fronds of Pteridium aquilinum and gallnuts of Quercus. The specific inhibitory activities (related to the dry mass of the extracts) suggest very efficient inhibitors having concentrations of half-inhibition in the muM-range. With 6 extracts the inhibitory activity on the NADH oxidase system was completely destroyed by boiling (Brassica oleracea, Amoracia rusticana, leaves of Digitalis purpurea, roots of Allium cepa, fruit pips of Malus domestica and mushrooms of Lactarius vellereus). The results with some plant species (Bryophyllum daigremonteanum, Allium cepa, male blossoms of Corylus avellana, Pteridium aquilinum) suggest a biological dynamics of the inhibitory activity. The inhibitor from Bryophyllum was partially characterized with regard to its mode of action. The following supposed biological functions of endogenous respiratory inhibitors of plants are discussed: 1. Involvement in the degradation of mitochondria in the course of differentiation, maturation and involution processes as well as in biologically controlled senescence processes; 2. A switch-over to the alternative mitochondrial respiratory pathway; 3. Induction and maintenance of a resting metabolism, e.g. in dormancy, by

  5. Bioenergetics and anaerobic respiratory chains of aceticlastic methanogens.

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    Welte, Cornelia; Deppenmeier, Uwe

    2014-07-01

    Methane-forming archaea are strictly anaerobic microbes and are essential for global carbon fluxes since they perform the terminal step in breakdown of organic matter in the absence of oxygen. Major part of methane produced in nature derives from the methyl group of acetate. Only members of the genera Methanosarcina and Methanosaeta are able to use this substrate for methane formation and growth. Since the free energy change coupled to methanogenesis from acetate is only -36kJ/mol CH4, aceticlastic methanogens developed efficient energy-conserving systems to handle this thermodynamic limitation. The membrane bound electron transport system of aceticlastic methanogens is a complex branched respiratory chain that can accept electrons from hydrogen, reduced coenzyme F420 or reduced ferredoxin. The terminal electron acceptor of this anaerobic respiration is a mixed disulfide composed of coenzyme M and coenzyme B. Reduced ferredoxin has an important function under aceticlastic growth conditions and novel and well-established membrane complexes oxidizing ferredoxin will be discussed in depth. Membrane bound electron transport is connected to energy conservation by proton or sodium ion translocating enzymes (F420H2 dehydrogenase, Rnf complex, Ech hydrogenase, methanophenazine-reducing hydrogenase and heterodisulfide reductase). The resulting electrochemical ion gradient constitutes the driving force for adenosine triphosphate synthesis. Methanogenesis, electron transport, and the structure of key enzymes are discussed in this review leading to a concept of how aceticlastic methanogens make a living. This article is part of a Special Issue entitled: 18th European Bioenergetic Conference. Copyright © 2013 Elsevier B.V. All rights reserved.

  6. Pontocerebellar hypoplasia associated with respiratory-chain defects

    NARCIS (Netherlands)

    de Koning, T. J.; de Vries, L. S.; Groenendaal, F.; Ruitenbeek, W.; Jansen, G. H.; Poll-The, B. T.; Barth, P. G.

    1999-01-01

    Pontocerebellar hypoplasias are congenital disorders of brain morphogenesis which include such diverse etiologies as carbohydrate-deficient glycoprotein syndrome type 1, cerebromuscular dystrophies (Walker-Warburg syndrome, Fukuyama syndrome, muscle-eye-brain disease) and at least two types of

  7. Stomatin-like protein 2 is required for in vivo mitochondrial respiratory chain supercomplex formation and optimal cell function.

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    Mitsopoulos, Panagiotis; Chang, Yu-Han; Wai, Timothy; König, Tim; Dunn, Stanley D; Langer, Thomas; Madrenas, Joaquín

    2015-05-01

    Stomatin-like protein 2 (SLP-2) is a mainly mitochondrial protein that is widely expressed and is highly conserved across evolution. We have previously shown that SLP-2 binds the mitochondrial lipid cardiolipin and interacts with prohibitin-1 and -2 to form specialized membrane microdomains in the mitochondrial inner membrane, which are associated with optimal mitochondrial respiration. To determine how SLP-2 functions, we performed bioenergetic analysis of primary T cells from T cell-selective Slp-2 knockout mice under conditions that forced energy production to come almost exclusively from oxidative phosphorylation. These cells had a phenotype characterized by increased uncoupled mitochondrial respiration and decreased mitochondrial membrane potential. Since formation of mitochondrial respiratory chain supercomplexes (RCS) may correlate with more efficient electron transfer during oxidative phosphorylation, we hypothesized that the defect in mitochondrial respiration in SLP-2-deficient T cells was due to deficient RCS formation. We found that in the absence of SLP-2, T cells had decreased levels and activities of complex I-III2 and I-III2-IV(1-3) RCS but no defects in assembly of individual respiratory complexes. Impaired RCS formation in SLP-2-deficient T cells correlated with significantly delayed T cell proliferation in response to activation under conditions of limiting glycolysis. Altogether, our findings identify SLP-2 as a key regulator of the formation of RCS in vivo and show that these supercomplexes are required for optimal cell function. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  8. Mitochondrial free radical overproduction due to respiratory chain impairment in the brain of a mouse model of Rett syndrome: protective effect of CNF1.

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    De Filippis, Bianca; Valenti, Daniela; de Bari, Lidia; De Rasmo, Domenico; Musto, Mattia; Fabbri, Alessia; Ricceri, Laura; Fiorentini, Carla; Laviola, Giovanni; Vacca, Rosa Anna

    2015-06-01

    Rett syndrome (RTT) is a pervasive neurodevelopmental disorder mainly caused by mutations in the X-linked MECP2 gene associated with severe intellectual disability, movement disorders, and autistic-like behaviors. Its pathogenesis remains mostly not understood and no effective therapy is available. High circulating levels of oxidative stress markers in patients and the occurrence of oxidative brain damage in MeCP2-deficient mouse models suggest the involvement of oxidative stress in RTT pathogenesis. However, the molecular mechanism and the origin of the oxidative stress have not been elucidated. Here we demonstrate that a redox imbalance arises from aberrant mitochondrial functionality in the brain of MeCP2-308 heterozygous female mice, a condition that more closely recapitulates that of RTT patients. The marked increase in the rate of hydrogen peroxide generation in the brain of RTT mice seems mainly produced by the dysfunctional complex II of the mitochondrial respiratory chain. In addition, both membrane potential generation and mitochondrial ATP synthesis are decreased in RTT mouse brains when succinate, the complex II respiratory substrate, is used as an energy source. Respiratory chain impairment is brain area specific, owing to a decrease in either cAMP-dependent phosphorylation or protein levels of specific complex subunits. Further, we investigated whether the treatment of RTT mice with the bacterial protein CNF1, previously reported to ameliorate the neurobehavioral phenotype and brain bioenergetic markers in an RTT mouse model, exerts specific effects on brain mitochondrial function and consequently on hydrogen peroxide production. In RTT brains treated with CNF1, we observed the reactivation of respiratory chain complexes, the rescue of mitochondrial functionality, and the prevention of brain hydrogen peroxide overproduction. These results provide definitive evidence of mitochondrial reactive oxygen species overproduction in RTT mouse brain and

  9. FGF-21 as a biomarker for muscle-manifesting mitochondrial respiratory chain deficiencies: a diagnostic study.

    NARCIS (Netherlands)

    Suomalainen, A.; Elo, J.M.; Pietilainen, K.H.; Hakonen, A.H.; Sevastianova, K.; Korpela, M.; Isohanni, P.; Marjavaara, S.K.; Tyni, T.; Kiuru-Enari, S.; Pihko, H.; Darin, N.; Ounap, K.; Kluijtmans, L.A.J.; Paetau, A.; Buzkova, J.; Bindoff, L.A.; Annunen-Rasila, J.; Uusimaa, J.; Rissanen, A.; Yki-Jarvinen, H.; Hirano, M.; Tulinius, M.; Smeitink, J.A.M.; Tyynismaa, H.

    2011-01-01

    BACKGROUND: Muscle biopsy is the gold standard for diagnosis of mitochondrial disorders because of the lack of sensitive biomarkers in serum. Fibroblast growth factor 21 (FGF-21) is a growth factor with regulatory roles in lipid metabolism and the starvation response, and concentrations are raised

  10. Neonatal lactic acidosis, complex I/IV deficiency, and fetal cerebral disruption

    NARCIS (Netherlands)

    van Straaten, HLM; van Tintelen, JP; Trijbels, JMF; van den Heuvel, LP; Troost, D; Rozemuller, JM; Duran, M; de Vries, LS; Schuelke, M; Barth, PG

    Cerebral developmental abnormalities occur in various inborn errors of metabolism including peroxisomal deficiencies, pyruvate dehydrogenase complex deficiency and others. Associations with abnormalities of the respiratory chain are rare. Here we report male and female siblings with microcephaly, a

  11. Putative Structural and Functional Coupling of the Mitochondrial BKCa Channel to the Respiratory Chain.

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    Piotr Bednarczyk

    Full Text Available Potassium channels have been found in the inner mitochondrial membranes of various cells. These channels regulate the mitochondrial membrane potential, the matrix volume and respiration. The activation of these channels is cytoprotective. In our study, the single-channel activity of a large-conductance Ca(2+-regulated potassium channel (mitoBKCa channel was measured by patch-clamping mitoplasts isolated from the human astrocytoma (glioblastoma U-87 MG cell line. A potassium-selective current was recorded with a mean conductance of 290 pS in symmetrical 150 mM KCl solution. The channel was activated by Ca(2+ at micromolar concentrations and by the potassium channel opener NS1619. The channel was inhibited by paxilline and iberiotoxin, known inhibitors of BKCa channels. Western blot analysis, immuno-gold electron microscopy, high-resolution immunofluorescence assays and polymerase chain reaction demonstrated the presence of the BKCa channel β4 subunit in the inner mitochondrial membrane of the human astrocytoma cells. We showed that substrates of the respiratory chain, such as NADH, succinate, and glutamate/malate, decrease the activity of the channel at positive voltages. This effect was abolished by rotenone, antimycin and cyanide, inhibitors of the respiratory chain. The putative interaction of the β4 subunit of mitoBKCa with cytochrome c oxidase was demonstrated using blue native electrophoresis. Our findings indicate possible structural and functional coupling of the mitoBKCa channel with the mitochondrial respiratory chain in human astrocytoma U-87 MG cells.

  12. A respiratory chain controlled signal transduction cascade in the mitochondrial intermembrane space mediates hydrogen peroxide signaling.

    Science.gov (United States)

    Patterson, Heide Christine; Gerbeth, Carolin; Thiru, Prathapan; Vögtle, Nora F; Knoll, Marko; Shahsafaei, Aliakbar; Samocha, Kaitlin E; Huang, Cher X; Harden, Mark Michael; Song, Rui; Chen, Cynthia; Kao, Jennifer; Shi, Jiahai; Salmon, Wendy; Shaul, Yoav D; Stokes, Matthew P; Silva, Jeffrey C; Bell, George W; MacArthur, Daniel G; Ruland, Jürgen; Meisinger, Chris; Lodish, Harvey F

    2015-10-20

    Reactive oxygen species (ROS) such as hydrogen peroxide (H2O2) govern cellular homeostasis by inducing signaling. H2O2 modulates the activity of phosphatases and many other signaling molecules through oxidation of critical cysteine residues, which led to the notion that initiation of ROS signaling is broad and nonspecific, and thus fundamentally distinct from other signaling pathways. Here, we report that H2O2 signaling bears hallmarks of a regular signal transduction cascade. It is controlled by hierarchical signaling events resulting in a focused response as the results place the mitochondrial respiratory chain upstream of tyrosine-protein kinase Lyn, Lyn upstream of tyrosine-protein kinase SYK (Syk), and Syk upstream of numerous targets involved in signaling, transcription, translation, metabolism, and cell cycle regulation. The active mediators of H2O2 signaling colocalize as H2O2 induces mitochondria-associated Lyn and Syk phosphorylation, and a pool of Lyn and Syk reside in the mitochondrial intermembrane space. Finally, the same intermediaries control the signaling response in tissues and species responsive to H2O2 as the respiratory chain, Lyn, and Syk were similarly required for H2O2 signaling in mouse B cells, fibroblasts, and chicken DT40 B cells. Consistent with a broad role, the Syk pathway is coexpressed across tissues, is of early metazoan origin, and displays evidence of evolutionary constraint in the human. These results suggest that H2O2 signaling is under control of a signal transduction pathway that links the respiratory chain to the mitochondrial intermembrane space-localized, ubiquitous, and ancient Syk pathway in hematopoietic and nonhematopoietic cells.

  13. The respiratory chain is the cell's Achilles' heel during UVA inactivation in Escherichia coli.

    Science.gov (United States)

    Bosshard, Franziska; Bucheli, Margarete; Meur, Yves; Egli, Thomas

    2010-07-01

    Solar disinfection (SODIS) is used as an effective and inexpensive tool to improve the microbiological quality of drinking water in developing countries where no other means are available. Solar UVA light is the agent that inactivates bacteria during the treatment. Damage to bacterial membranes plays a crucial role in the inactivation process. This study showed that even slightly irradiated cells (after less than 1 h of simulated sunlight) were strongly affected in their ability to maintain essential parts of their energy metabolism, in particular of the respiratory chain (activities of NADH oxidase, succinate oxidase and lactate oxidase were measured). The cells' potential to generate ATP was also strongly inhibited. Many essential enzymes of carbon metabolism (glucose-6-phosphate dehydrogenase, glyceraldehyde-3-phosphate dehydrogenase, lactate dehydrogenase and malate dehydrogenase) and defence against oxidative stress (catalases and glutathione-disulfide reductase) were reduced in their activity during SODIS. The work suggests that damage to membrane enzymes is a likely cause of membrane dysfunction (loss of membrane potential and increased membrane permeability) during UVA irradiation. In this study, the first targets on the way to cell death were found to be the respiratory chain and F(1)F(0) ATPase.

  14. Importance of the core structure of flavones in promoting inhibition of the mitochondrial respiratory chain.

    Science.gov (United States)

    Valdameri, Glaucio; Herrerias, Tatiana; Carnieri, Eva Gunilla Skare; Cadena, Silvia Maria Suter Correia; Martinez, Glaucia Regina; Rocha, Maria Eliane Merlin

    2010-10-06

    Flavonoids are a large group of polyphenolic compounds that have received considerable attention because of their biological and physiological importance. The flavone (2-phenyl-4H-1-benzopyran-4one) used in this work is found in some cereal grains and generates several biological activities, including: apoptosis induction, cell cycle arrest, caspase activation and inhibition of tumor cell proliferation. However, its effects on the hepatic mitochondrial metabolism are still unknown. We evaluated the effect of flavone on the metabolism of mitochondria isolated from rat liver. Polarographic experiments using 200 micromol L(-1) flavone and rat liver mitochondria oxidizing glutamate or succinate indicated that both substrates underwent: (i) reduction of state 3 respiration; (ii) stimulation of state 4 respiration; (iii) reduction of the respiratory control coefficient; and (iv) reduction of the ADP/O ratio. An analysis of the activity of enzymatic complexes in the respiratory chain showed that flavone acts between complexes I and III. Flavone reduced the membrane electric potential at doses of 100, 150 and 200 micromol L(-1). Flavone at certain doses (75-200 micromol L(-1)) reduced mitochondrial swelling in the presence of valinomycin and KNO(3), suggesting that flavone could induce changes in mitochondrial membrane properties. These results demonstrate that the inhibition of mitochondrial enzymes in the respiratory chain coupled with the effects on membrane properties are promoted by the core structure of flavones, and these effects may be in part responsible for the cytotoxic effects of flavones. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

  15. The mechanism of coupling between oxido-reduction and proton translocation in respiratory chain enzymes.

    Science.gov (United States)

    Papa, Sergio; Capitanio, Giuseppe; Papa, Francesco

    2017-06-21

    The respiratory chain of mitochondria and bacteria is made up of a set of membrane-associated enzyme complexes which catalyse sequential, stepwise transfer of reducing equivalents from substrates to oxygen and convert redox energy into a transmembrane protonmotive force (PMF) by proton translocation from a negative (N) to a positive (P) aqueous phase separated by the coupling membrane. There are three basic mechanisms by which a membrane-associated redox enzyme can generate a PMF. These are membrane anisotropic arrangement of the primary redox catalysis with: (i) vectorial electron transfer by redox metal centres from the P to the N side of the membrane; (ii) hydrogen transfer by movement of quinones across the membrane, from a reduction site at the N side to an oxidation site at the P side; (iii) a different type of mechanism based on co-operative allosteric linkage between electron transfer at the metal redox centres and transmembrane electrogenic proton translocation by apoproteins. The results of advanced experimental and theoretical analyses and in particular X-ray crystallography show that these three mechanisms contribute differently to the protonmotive activity of cytochrome c oxidase, ubiquinone-cytochrome c oxidoreductase and NADH-ubiquinone oxidoreductase of the respiratory chain. This review considers the main features, recent experimental advances and still unresolved problems in the molecular/atomic mechanism of coupling between the transfer of reducing equivalents and proton translocation in these three protonmotive redox complexes. © 2017 Cambridge Philosophical Society.

  16. Combined deficiency of coagulation factors V and VIII: an update.

    Science.gov (United States)

    Zheng, Chunlei; Zhang, Bin

    2013-09-01

    Combined deficiency of factor V (FV) and FVIII (F5F8D) is an autosomal recessive bleeding disorder characterized by simultaneous decreases of both coagulation factors. This review summarizes recent reports on the clinical presentations, treatments, and molecular mechanism of F5F8D. Genetic studies identified LMAN1 and MCFD2 as causative genes for this disorder, revealing a previously unknown intracellular transport pathway shared by the two important blood coagulation factors. LMAN1 and MCFD2 form a Ca2+-dependent cargo receptor complex that functions in the transport of FV/FVIII from the endoplasmic reticulum (ER) to the Golgi. Disrupting the LMAN1-MCFD2 receptor, complex formation is the primary molecular defect of missense mutations leading to F5F8D. The EF-hand domains of MCFD2 are necessary and sufficient for the interactions with both LMAN1 and FV/FVIII. Similarly, the carbohydrate recognition domain of LMAN1 contains distinct and separable binding sites for both MCFD2 and FV/FVIII. Therefore, FV and FVIII likely carry duel sorting signals that are separately recognized by LMAN1 and MCFD2 and necessary for the efficient ER-to-Golgi transport. FV and FVIII likely bind LMAN1 through the high-mannose N-linked glycans under the higher Ca2+ conditions in the ER and dissociate in the lower Ca2+ environment of the ER-Golgi intermediate compartment. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  17. The respiratory chains of four strains of the alkaliphilic Bacillus clausii

    Directory of Open Access Journals (Sweden)

    A. Abbrescia

    2014-01-01

    Full Text Available A comparative analysis of terminal respiratory enzymes has been performed on four strains of Bacillus clausii used for preparation of a European probiotic. These four strains originated most probably from a common ancestor through early selection of stable clones for industrial propagation. They exhibit a low level of intra-specific diversity and a high degree of genomic conservation, making them an attractive model to study the different bioenergetics behaviors of alkaliphilic bacilli. The analysis of the different bioenergetics responses has been carried out revealing striking differences among the strains. Two out of the four strains have shown a functional redundancy of the terminal part of the respiratory chain. The biochemical data correlate with the expression level of the mRNA of cytochrome c oxidase and quinol oxidase genes (heme-copper type. The consequences of these different bioenergetics behaviors are also discussed.

  18. Respiratory chain complexes in dynamic mitochondria display a patchy distribution in life cells.

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    Britta Muster

    Full Text Available BACKGROUND: Mitochondria, the main suppliers of cellular energy, are dynamic organelles that fuse and divide frequently. Constraining these processes impairs mitochondrial is closely linked to certain neurodegenerative diseases. It is proposed that functional mitochondrial dynamics allows the exchange of compounds thereby providing a rescue mechanism. METHODOLOGY/PRINCIPAL FINDINGS: The question discussed in this paper is whether fusion and fission of mitochondria in different cell lines result in re-localization of respiratory chain (RC complexes and of the ATP synthase. This was addressed by fusing cells containing mitochondria with respiratory complexes labelled with different fluorescent proteins and resolving their time dependent re-localization in living cells. We found a complete reshuffling of RC complexes throughout the entire chondriome in single HeLa cells within 2-3 h by organelle fusion and fission. Polykaryons of fused cells completely re-mixed their RC complexes in 10-24 h in a progressive way. In contrast to the recently described homogeneous mixing of matrix-targeted proteins or outer membrane proteins, the distribution of RC complexes and ATP synthase in fused hybrid mitochondria, however, was not homogeneous but patterned. Thus, complete equilibration of respiratory chain complexes as integral inner mitochondrial membrane complexes is a slow process compared with matrix proteins probably limited by complete fusion. In co-expressing cells, complex II is more homogenously distributed than complex I and V, resp. Indeed, this result argues for higher mobility and less integration in supercomplexes. CONCLUSION/SIGNIFICANCE: Our results clearly demonstrate that mitochondrial fusion and fission dynamics favours the re-mixing of all RC complexes within the chondriome. This permanent mixing avoids a static situation with a fixed composition of RC complexes per mitochondrion.

  19. A Functional Approach towards Understanding the Role of the Mitochondrial Respiratory Chain in an Endomycorrhizal Symbiosis

    Science.gov (United States)

    Mercy, Louis; Lucic-Mercy, Eva; Nogales, Amaia; Poghosyan, Areg; Schneider, Carolin; Arnholdt-Schmitt, Birgit

    2017-01-01

    Arbuscular mycorrhizal fungi (AMF) are crucial components of fertile soils, able to provide several ecosystem services for crop production. Current economic, social and legislative contexts should drive the so-called “second green revolution” by better exploiting these beneficial microorganisms. Many challenges still need to be overcome to better understand the mycorrhizal symbiosis, among which (i) the biotrophic nature of AMF, constraining their production, while (ii) phosphate acts as a limiting factor for the optimal mycorrhizal inoculum application and effectiveness. Organism fitness and adaptation to the changing environment can be driven by the modulation of mitochondrial respiratory chain, strongly connected to the phosphorus processing. Nevertheless, the role of the respiratory function in mycorrhiza remains largely unexplored. We hypothesized that the two mitochondrial respiratory chain components, alternative oxidase (AOX) and cytochrome oxidase (COX), are involved in specific mycorrhizal behavior. For this, a complex approach was developed. At the pre-symbiotic phase (axenic conditions), we studied phenotypic responses of Rhizoglomus irregulare spores with two AOX and COX inhibitors [respectively, salicylhydroxamic acid (SHAM) and potassium cyanide (KCN)] and two growth regulators (abscisic acid – ABA and gibberellic acid – Ga3). At the symbiotic phase, we analyzed phenotypic and transcriptomic (genes involved in respiration, transport, and fermentation) responses in Solanum tuberosum/Rhizoglomus irregulare biosystem (glasshouse conditions): we monitored the effects driven by ABA, and explored the modulations induced by SHAM and KCN under five phosphorus concentrations. KCN and SHAM inhibited in vitro spore germination while ABA and Ga3 induced differential spore germination and hyphal patterns. ABA promoted mycorrhizal colonization, strong arbuscule intensity and positive mycorrhizal growth dependency (MGD). In ABA treated plants, R. irregulare

  20. Neuroradiologic findings in children with mitochondrial disorder: correlation with mitochondrial respiratory chain defects

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jinna; Lee, Seung-Koo; Kim, Dong Ik [Yonsei University College of Medicine, Department of Radiology, Research Institute of Radiological Science, Seoul (Korea); Kim, Eung Yeop [Yonsei University College of Medicine, Department of Radiology, Research Institute of Radiological Science, Brain Korea 21 Project for Medical Science, Seoul (Korea); Lee, Young-Mock; Lee, Joon Soo [Yonsei University College of Medicine, Department of Pediatrics, Pediatric Epilepsy Clinics, Severance Children' s Hospital, Brain Research Institute, Seoul (Korea); Kim, Heung Dong [Yonsei University College of Medicine, Department of Pediatrics, Pediatric Epilepsy Clinics, Severance Children' s Hospital, Brain Research Institute, Seoul (Korea); Yonsei University College of Medicine, Department of Pediatrics, Seoul (Korea)

    2008-08-15

    Mitochondrial disorders are a heterogeneous group of disorders affecting energy metabolism that can present at any age with a wide variety of clinical symptoms. We investigated brain magnetic resonance (MR) findings in 40 children with defects of the mitochondrial respiratory chain (MRC) complex and correlated them with the type of MRC defects. Enrolled were 40 children with MRC defects in biochemical enzyme assay of the muscle specimen. Twenty-one children were found to have classical syndromes of mitochondrial disorders and 19 children presented nonspecific mitochondrial encephalomyopathies. Their brain MR imaging findings were retrospectively reviewed and correlated with the biochemical defect in the MRC complex. Children with MRC defects showed various neuroradiologic features on brain MR imaging that resulted from a complex genetic background and a heterogeneous phenotype. Rapid progression of atrophy involving all structures of the brain with variable involvement of deep gray and white matter are the most frequent MR findings in children with MRC defects in both classical syndromes of mitochondrial disorder and nonspecific mitochondrial encephalomyopathies. The type of biochemical defect in the MRC complex enzyme did not correlate with brain MR findings in child patients. (orig.)

  1. Compound heterozygous mutations in glycyl-tRNA synthetase (GARS cause mitochondrial respiratory chain dysfunction.

    Directory of Open Access Journals (Sweden)

    Michael Nafisinia

    Full Text Available Glycyl-tRNA synthetase (GARS; OMIM 600287 is one of thirty-seven tRNA-synthetase genes that catalyses the synthesis of glycyl-tRNA, which is required to insert glycine into proteins within the cytosol and mitochondria. To date, eighteen mutations in GARS have been reported in patients with autosomal-dominant Charcot-Marie-Tooth disease type 2D (CMT2D; OMIM 601472, and/or distal spinal muscular atrophy type V (dSMA-V; OMIM 600794. In this study, we report a patient with clinical and biochemical features suggestive of a mitochondrial respiratory chain (MRC disorder including mild left ventricular posterior wall hypertrophy, exercise intolerance, and lactic acidosis. Using whole exome sequencing we identified compound heterozygous novel variants, c.803C>T; p.(Thr268Ile and c.1234C>T; p.(Arg412Cys, in GARS in the proband. Spectrophotometric evaluation of the MRC complexes showed reduced activity of Complex I, III and IV in patient skeletal muscle and reduced Complex I and IV activity in the patient liver, with Complex IV being the most severely affected in both tissues. Immunoblot analysis of GARS protein and subunits of the MRC enzyme complexes in patient fibroblast extracts showed significant reduction in GARS protein levels and Complex IV. Together these studies provide evidence that the identified compound heterozygous GARS variants may be the cause of the mitochondrial dysfunction in our patient.

  2. Deficiencies

    Data.gov (United States)

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

  3. Generation of recombination activating gene-1-deficient neonatal piglets: a model of T and B cell deficient severe combined immune deficiency.

    Directory of Open Access Journals (Sweden)

    Tetsuya Ito

    Full Text Available Although severe combined immune deficiency (SCID is a very important research model for mice and SCID mice are widely used, there are only few reports describing the SCID pig models. Therefore, additional research in this area is needed. In this study, we describe the generation of Recombination activating gene-1 (Rag-1-deficient neonatal piglets in Duroc breed using somatic cell nuclear transfer (SCNT with gene targeting and analysis using fluorescence-activated cell sorting (FACS and histology. We constructed porcine Rag-1 gene targeting vectors for the Exon 2 region and obtained heterozygous/homozygous Rag-1 knockout cell colonies using SCNT. We generated two Rag-1-deficient neonatal piglets and compared them with wild-type neonatal piglets. FACS analysis showed that Rag-1 disruption causes a lack of Immunoglobulin M-positive B cells and CD3-positive T cells in peripheral blood mononuclear cells. Consistent with FACS analysis, histological analysis revealed structural defects and an absence of mature lymphocytes in the spleen, mesenteric lymph node (MLNs, and thymus in Rag-1-deficient piglets. These results confirm that Rag-1 is necessary for the generation of lymphocytes in pigs, and Rag-1-deficient piglets exhibit a T and B cell deficient SCID (T-B-SCID phenotype similar to that of rodents and humans. The T-B-SCID pigs with Rag-1 deficiency generated in this study could be a suitably versatile model for laboratory, translational, and biomedical research, including the development of a humanized model and assessment of pluripotent stem cells.

  4. The effect of artichoke (Cynara scolymus L.) extract on respiratory chain system activity in rat liver mitochondria.

    Science.gov (United States)

    Juzyszyn, Z; Czerny, B; Myśliwiec, Z; Pawlik, A; Droździk, M

    2010-06-01

    The effect of artichoke extract on mitochondrial respiratory chain (MRC) activity in isolated rat liver mitochondria (including reaction kinetics) was studied. The effect of the extract on the activity of isolated cytochrome oxidase was also studied. Extract in the range of 0.68-2.72 microg/ml demonstrated potent and concentration-dependent inhibitory activity. Concentrations > or =5.4 microg/ml entirely inhibited MRC activity. The succinate oxidase system (MRC complexes II-IV) was the most potently inhibited, its activity at an extract concentration of 1.36 microg/ml being reduced by 63.3% compared with the control (p artichoke extracts may rely in part on the effects of their active compounds on the activity of the mitochondrial respiratory chain system.

  5. Repairing oxidized proteins in the bacterial envelope using respiratory chain electrons.

    Science.gov (United States)

    Gennaris, Alexandra; Ezraty, Benjamin; Henry, Camille; Agrebi, Rym; Vergnes, Alexandra; Oheix, Emmanuel; Bos, Julia; Leverrier, Pauline; Espinosa, Leon; Szewczyk, Joanna; Vertommen, Didier; Iranzo, Olga; Collet, Jean-François; Barras, Frédéric

    2015-12-17

    The reactive species of oxygen and chlorine damage cellular components, potentially leading to cell death. In proteins, the sulfur-containing amino acid methionine is converted to methionine sulfoxide, which can cause a loss of biological activity. To rescue proteins with methionine sulfoxide residues, living cells express methionine sulfoxide reductases (Msrs) in most subcellular compartments, including the cytosol, mitochondria and chloroplasts. Here we report the identification of an enzymatic system, MsrPQ, repairing proteins containing methionine sulfoxide in the bacterial cell envelope, a compartment particularly exposed to the reactive species of oxygen and chlorine generated by the host defence mechanisms. MsrP, a molybdo-enzyme, and MsrQ, a haem-binding membrane protein, are widely conserved throughout Gram-negative bacteria, including major human pathogens. MsrPQ synthesis is induced by hypochlorous acid, a powerful antimicrobial released by neutrophils. Consistently, MsrPQ is essential for the maintenance of envelope integrity under bleach stress, rescuing a wide series of structurally unrelated periplasmic proteins from methionine oxidation, including the primary periplasmic chaperone SurA. For this activity, MsrPQ uses electrons from the respiratory chain, which represents a novel mechanism to import reducing equivalents into the bacterial cell envelope. A remarkable feature of MsrPQ is its capacity to reduce both rectus (R-) and sinister (S-) diastereoisomers of methionine sulfoxide, making this oxidoreductase complex functionally different from previously identified Msrs. The discovery that a large class of bacteria contain a single, non-stereospecific enzymatic complex fully protecting methionine residues from oxidation should prompt a search for similar systems in eukaryotic subcellular oxidizing compartments, including the endoplasmic reticulum.

  6. New MT-ND6 and NDUFA1 mutations in mitochondrial respiratory chain disorders.

    Science.gov (United States)

    Uehara, Natsumi; Mori, Masato; Tokuzawa, Yoshimi; Mizuno, Yosuke; Tamaru, Shunsuke; Kohda, Masakazu; Moriyama, Yohsuke; Nakachi, Yutaka; Matoba, Nana; Sakai, Tetsuro; Yamazaki, Taro; Harashima, Hiroko; Murayama, Kei; Hattori, Keisuke; Hayashi, Jun-Ichi; Yamagata, Takanori; Fujita, Yasunori; Ito, Masafumi; Tanaka, Masashi; Nibu, Ken-Ichi; Ohtake, Akira; Okazaki, Yasushi

    2014-05-01

    Mitochondrial respiratory chain disorder (MRCD) is an intractable disease of infants with variable clinical symptoms. Our goal was to identify the causative mutations in MRCD patients. The subjects were 90 children diagnosed with MRCD by enzyme assay. We analyzed whole mitochondrial DNA (mtDNA) sequences. A cybrid study was performed in two patients. Whole exome sequencing was performed for one of these two patients whose mtDNA variant was confirmed as non-pathogenic. Whole mtDNA sequences identified 29 mtDNA variants in 29 patients (13 were previously reported, the other 13 variants and three deletions were novel). The remaining 61 patients had no pathogenic mutations in their mtDNA. Of the 13 patients harboring unreported mtDNA variants, we excluded seven variants by manual curation. Of the remaining six variants, we selected two Leigh syndrome patients whose mitochondrial enzyme activity was decreased in their fibroblasts and performed a cybrid study. We confirmed that m.14439G>A (MT-ND6) was pathogenic, while m.1356A>G (mitochondrial 12S rRNA) was shown to be a non-pathogenic polymorphism. Exome sequencing and a complementation study of the latter patient identified a novel c.55C>T hemizygous missense mutation in the nuclear-encoded gene NDUFA1. Our results demonstrate that it is important to perform whole mtDNA sequencing rather than only typing reported mutations. Cybrid assays are also useful to diagnose the pathogenicity of mtDNA variants, and whole exome sequencing is a powerful tool to diagnose nuclear gene mutations as molecular diagnosis can provide a lead to appropriate genetic counseling.

  7. Multistationary and oscillatory modes of free radicals generation by the mitochondrial respiratory chain revealed by a bifurcation analysis.

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    Vitaly A Selivanov

    Full Text Available The mitochondrial electron transport chain transforms energy satisfying cellular demand and generates reactive oxygen species (ROS that act as metabolic signals or destructive factors. Therefore, knowledge of the possible modes and bifurcations of electron transport that affect ROS signaling provides insight into the interrelationship of mitochondrial respiration with cellular metabolism. Here, a bifurcation analysis of a sequence of the electron transport chain models of increasing complexity was used to analyze the contribution of individual components to the modes of respiratory chain behavior. Our algorithm constructed models as large systems of ordinary differential equations describing the time evolution of the distribution of redox states of the respiratory complexes. The most complete model of the respiratory chain and linked metabolic reactions predicted that condensed mitochondria produce more ROS at low succinate concentration and less ROS at high succinate levels than swelled mitochondria. This prediction was validated by measuring ROS production under various swelling conditions. A numerical bifurcation analysis revealed qualitatively different types of multistationary behavior and sustained oscillations in the parameter space near a region that was previously found to describe the behavior of isolated mitochondria. The oscillations in transmembrane potential and ROS generation, observed in living cells were reproduced in the model that includes interaction of respiratory complexes with the reactions of TCA cycle. Whereas multistationarity is an internal characteristic of the respiratory chain, the functional link of respiration with central metabolism creates oscillations, which can be understood as a means of auto-regulation of cell metabolism.

  8. Behavioral responses and fluid regulation in male rats after combined dietary sodium deficiency and water deprivation.

    Science.gov (United States)

    Lucia, Kimberly J; Curtis, Kathleen S

    2018-02-01

    Most investigators use a single treatment such as water deprivation or dietary sodium deficiency to evaluate thirst or sodium appetite, which underlie behavioral responses to body fluid challenges. The goal of the present experiments was to assess the effects of combined treatments in driving behaviors. Therefore, we evaluated the effect of combined overnight water deprivation and dietary sodium deficiency on water intake and salt intake by adult male rats in 2-bottle (0.5M NaCl and water) tests. Overnight water deprivation alone increased water intake, and 10days of dietary sodium deficiency increased 0.5M NaCl intake, with a secondary increase in water intake. During combined water deprivation and dietary sodium deficiency, water intake was enhanced and 0.5M NaCl was reduced, but not eliminated, suggesting that physiologically relevant behavioral responses persist. Nonetheless, the pattern of fluid intake was altered by the combined treatments. We also assessed the effect of these behaviors on induced deficits in body sodium and fluid volume during combined treatments and found that, regardless of treatment, fluid ingestion partially repleted the induced deficits. Finally, we examined urine volume and sodium excretion during dietary sodium deficiency with or without overnight water deprivation and found that, whether or not rats were water deprived, and regardless of water consumption, sodium excretion was minimal. Thus, the combination of water deprivation and dietary sodium deficiency appears to arouse drives that stimulate compensatory behavioral responses. These behaviors, in conjunction with physiological adaptations to the treatments, underlie body sodium and volume repletion in the face of combined water deprivation and dietary sodium deficiency. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Gene Therapy for RAG-deficient Severe Combined Immunodeficiency

    NARCIS (Netherlands)

    K. Pike (Karin)

    2007-01-01

    textabstractSevere combined immunodeficiency (SCID) is a rare class of primary, inherited, immunodeficiency causing infants to suffer from persistent diarrhea, opportunistic infections and a failure to thrive. RAG proteins play a crucial role in the initiation of V(D)J recombination of

  10. Subacute combined spinal cord degeneration and pancytopenia secondary to severe vitamin B12 deficiency

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    José Luis Cabrerizo-García

    Full Text Available CONTEXT: Decreased vitamin B12 concentration does not usually result in clinical or hematological abnormalities. Subacute combined spinal cord degeneration and pancytopenia are two serious and rarely displayed consequences that appear in severe deficits. CASE REPORT: We present the case of a patient with subacute combined spinal cord degeneration and pancytopenia secondary to severe and sustained vitamin B12 deficiency. Such cases are rare nowadays and have potentially fatal consequences. CONCLUSIONS: Vitamin B12 deficiency should be taken into consideration in the differential diagnosis in cases of blood disorders or severe neurological symptoms. Early diagnosis and treatment can avoid irreversible consequences.

  11. Evidence that metformin exerts its anti-diabetic effects through inhibition of complex 1 of the mitochondrial respiratory chain.

    Science.gov (United States)

    Owen, M R; Doran, E; Halestrap, A P

    2000-01-01

    Although metformin is widely used for the treatment of non-insulin-dependent diabetes, its mode of action remains unclear. Here we provide evidence that its primary site of action is through a direct inhibition of complex 1 of the respiratory chain. Metformin(50 microM) inhibited mitochondrial oxidation of glutamate+malate in hepatoma cells by 13 and 30% after 24 and 60 h exposure respectively, but succinate oxidation was unaffected. Metformin also caused time-dependent inhibition of complex 1 in isolated mitochondria, whereas in sub-mitochondrial particles inhibition was immediate but required very high metformin concentrations (K(0.5),79 mM). These data are compatible with the slow membrane-potential-driven accumulation of the positively charged drug within the mitochondrial matrix leading to inhibition of complex 1. Metformin inhibition of gluconeogenesis from L-lactate in isolated rat hepatocytes was also time- and concentration-dependent, and accompanied by changes in metabolite levels similar to those induced by other inhibitors of gluconeogenesis acting on complex 1. Freeze-clamped livers from metformin-treated rats exhibited similar changes in metabolite concentrations. We conclude that the drug's pharmacological effects are mediated, at least in part, through a time-dependent, self-limiting inhibition of the respiratory chain that restrains hepatic gluconeogenesis while increasing glucose utilization in peripheral tissues. Lactic acidosis, an occasional side effect, canal so be explained in this way. PMID:10839993

  12. Chronic inhibition of the respiratory chain in human fibroblast cultures: differential responses related to subject chronological and biological age.

    Science.gov (United States)

    Dekker, Pim; van Baalen, Laurens M; Dirks, Roeland W; Slagboom, P Eline; van Heemst, Diana; Tanke, Hans J; Westendorp, Rudi G J; Maier, Andrea B

    2012-05-01

    Respiratory chain function becomes less efficient with age resulting in increased levels of damaging reactive oxygen species. We compared rotenone-exposed fibroblast strains from young and old subjects and from offspring of nonagenarian siblings and the partners of the offspring. Rotenone increased reactive oxygen species levels, inhibited growth rate, and increased telomere shortening (all p < .05). Non-stressed strains from young subjects showed lower reactive oxygen species levels (p = .031) and higher growth rates (p = .002) than strains from old subjects. Stressed strains from young subjects showed smaller increases in reactive oxygen species levels (p = .014) and larger decreases in growth rate (p < .001) than strains from old subjects. Telomere-shortening rates were not different between groups. Stress-induced decreases in growth rate were larger in strains from offspring than from partners (p = .05). Strains from young and old subjects are differentially affected by chronic inhibition of the respiratory chain. Changed growth rates in strains from offspring resemble those from strains from young subjects.

  13. M19 modulates skeletal muscle differentiation and insulin secretion in pancreatic β-cells through modulation of respiratory chain activity.

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    Linda Cambier

    Full Text Available Mitochondrial dysfunction due to nuclear or mitochondrial DNA alterations contributes to multiple diseases such as metabolic myopathies, neurodegenerative disorders, diabetes and cancer. Nevertheless, to date, only half of the estimated 1,500 mitochondrial proteins has been identified, and the function of most of these proteins remains to be determined. Here, we characterize the function of M19, a novel mitochondrial nucleoid protein, in muscle and pancreatic β-cells. We have identified a 13-long amino acid sequence located at the N-terminus of M19 that targets the protein to mitochondria. Furthermore, using RNA interference and over-expression strategies, we demonstrate that M19 modulates mitochondrial oxygen consumption and ATP production, and could therefore regulate the respiratory chain activity. In an effort to determine whether M19 could play a role in the regulation of various cell activities, we show that this nucleoid protein, probably through its modulation of mitochondrial ATP production, acts on late muscle differentiation in myogenic C2C12 cells, and plays a permissive role on insulin secretion under basal glucose conditions in INS-1 pancreatic β-cells. Our results are therefore establishing a functional link between a mitochondrial nucleoid protein and the modulation of respiratory chain activities leading to the regulation of major cellular processes such as myogenesis and insulin secretion.

  14. Oxidation-reduction and reactive oxygen species homeostasis in mutant plants with respiratory chain complex I dysfunction.

    Science.gov (United States)

    Juszczuk, Izabela M; Szal, Bożena; Rychter, Anna M

    2012-02-01

    Mutations in a mitochondrial or nuclear gene encoding respiratory chain complex I subunits lead to decreased or a total absence of complex I activity. Plant mutants with altered or lost complex I activity adapt their respiratory metabolism by inducing alternative pathways of the respiratory chain and changing energy metabolism. Apparently, complex I is a crucial component of the oxidation-reduction (redox) regulatory system in photosynthetic cells, and alternative NAD(P)H dehydrogenases of the mitochondrial electron transport chain (mtETC) cannot fully compensate for its impairment. In most cases, dysfunction of complex I is associated with lowered or unchanged hydrogen peroxide (H(2)O(2)) concentrations, but increased superoxide (O(2)(-)) levels. Higher production of reactive oxygen species (ROS) by mitochondria in the mosaic (MSC16) cucumber mutant may be related to retrograde signalling. Different effects of complex I dysfunction on H(2)O(2) and O(2)(-) levels in described mutants might result from diverse regulation of processes involved in H(2)O(2) and O(2)(-) production. Often, dysfunction of complex I did not lead to oxidative stress, but increased the capacity of the antioxidative system and enhanced stress tolerance. The new cellular homeostasis in mutants with dysfunction of complex I allows growth and development, reflecting the plasticity of plant metabolism. © 2011 Blackwell Publishing Ltd.

  15. Respiratory-chain enzyme activities in isolated mitochondria of lymphocytes from untreated Parkinson's disease patients. Grupo-Centro de Trastornos del Movimiento.

    Science.gov (United States)

    Martín, M A; Molina, J A; Jiménez-Jiménez, F J; Benito-León, J; Ortí-Pareja, M; Campos, Y; Arenas, J

    1996-05-01

    We studied respiratory-chain enzyme activities in lymphocyte mitochondria from 36 untreated Parkinson's disease (PD) patients and in 30 age- and sex-matched healthy controls. The respiratory-chain enzyme activities did not differ significantly between patients and controls. Moreover, no patient showed respiratory-chain enzyme levels below normal range. Values for activities of complexes in the PD group did not correlate with age at onset, duration, scores of the Unified Parkinson's Disease Rating scales, or Hoehn and Yahr staging. These results suggest that the presence of defects of respiratory-chain complexes could depend on methodologic aspects, and that determinations of respiratory-chain enzymes in cell homogenates are not generally appropriate for evaluating abnormal mitochondrial dysfunction, especially when the amount of the specific enzyme is relatively low, as is the case of blood cells. In addition, the method of measuring complex I activity is critical for evaluating the results. In conclusion, our finding of normal mitochondrial function in lymphocyte mitochondria suggests that this tissue cannot be used to develop a diagnostic test for PD.

  16. [Effects of exogenous carnitine on function of respiratory chain and antioxidant capacity in mitochondria of myocardium after exhaustive running in rats].

    Science.gov (United States)

    Li, Jie; Yu, Xiao-Yan

    2012-09-01

    To investigate the effect of exogenous carnitine on function of respiratory chain and antioxidant capacity in mitochondria of myocardium in rats. Forty male Wistar rats were randomized to 4 groups (n = 10): static control (C), supplementation of carnitine (LC), exercise-training (T) and training with supplementation of carnitine (TLC). LC and TLC animals were perfused carnitine by the dose of 300 mg/kg bw x d. T and TLC animals were forced to performed 6-week treadmill training. Heart were prepared immediately after exhaustive running. Myocardium mitochondria was extracted by differential centrifugation. Spectrophotometric analysis was used to evaluate activities of respiratory chain complex (C) I -IV and superoxide dismutase (SOD), malondialdehyde (MDA) level in myocardium mitochondria. To compare with C group, C I and C IV activity in LC, T and TLC group were increased significantly (P function of respiratory chain and increased antioxidant capacity in myocardium mitochondria, there was better function of cooperation between carnitine and training.

  17. Two Cases of Severe Combined Immunodeficiency Caused By Adenosine Deaminase Deficiency

    Directory of Open Access Journals (Sweden)

    Turkan Patiroglu

    2014-08-01

    Full Text Available Severe Combined Immune Deficiency (SCID is a primary immune deficiency disorder manifested with severe infections upon first months of life, which is characterized by diverse genetic defects in T and B lymphocyte functions and occasionally in NK cells. ADA deficiency is a form of SCID progressing with severe lymphopenia and immune deficiency caused by toxic metabolites of ADA. Bone marrow transplantation (BMT is the only curative treatment although prophylactic anti-microbial therapy, intravenous immunoglobulin (IVIG and enzyme replacement can achieve transient improvements. Early diagnosis before development of severe infections and organ injury and referral to pediatric immunology clinics will make considerable contributions to prognosis. Here, we presented 2 cousins with SCID who had positive family history with deceased sibling; presented with tanning at skin, severe neonatal infections and Q246X (c736C>T non-sense mutation in exon 8 in ADA gene  in order to emphasize this rare mutation and pediatric emergencies associated with this disorder.

  18. The Multicenter Aerobic Iron Respiratory Chain of Acidithiobacillus ferrooxidans Functions as an Ensemble with a Single Macroscopic Rate Constant.

    Science.gov (United States)

    Li, Ting-Feng; Painter, Richard G; Ban, Bhupal; Blake, Robert C

    2015-07-24

    Electron transfer reactions among three prominent colored proteins in intact cells of Acidithiobacillus ferrooxidans were monitored using an integrating cavity absorption meter that permitted the acquisition of accurate absorbance data in suspensions of cells that scattered light. The concentrations of proteins in the periplasmic space were estimated to be 350 and 25 mg/ml for rusticyanin and cytochrome c, respectively; cytochrome a was present as one molecule for every 91 nm(2) in the cytoplasmic membrane. All three proteins were rapidly reduced to the same relative extent when suspensions of live bacteria were mixed with different concentrations of ferrous ions at pH 1.5. The subsequent molecular oxygen-dependent oxidation of the multicenter respiratory chain occurred with a single macroscopic rate constant, regardless of the proteins' in vitro redox potentials or their putative positions in the aerobic iron respiratory chain. The crowded electron transport proteins in the periplasm of the organism constituted an electron conductive medium where the network of protein interactions functioned in a concerted fashion as a single ensemble with a standard reduction potential of 650 mV. The appearance of product ferric ions was correlated with the reduction levels of the periplasmic electron transfer proteins; the limiting first-order catalytic rate constant for aerobic respiration on iron was 7,400 s(-1). The ability to conduct direct spectrophotometric studies under noninvasive physiological conditions represents a new and powerful approach to examine the extent and rates of biological events in situ without disrupting the complexity of the live cellular environment. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  19. The Multicenter Aerobic Iron Respiratory Chain of Acidithiobacillus ferrooxidans Functions as an Ensemble with a Single Macroscopic Rate Constant*

    Science.gov (United States)

    Li, Ting-Feng; Painter, Richard G.; Ban, Bhupal; Blake, Robert C.

    2015-01-01

    Electron transfer reactions among three prominent colored proteins in intact cells of Acidithiobacillus ferrooxidans were monitored using an integrating cavity absorption meter that permitted the acquisition of accurate absorbance data in suspensions of cells that scattered light. The concentrations of proteins in the periplasmic space were estimated to be 350 and 25 mg/ml for rusticyanin and cytochrome c, respectively; cytochrome a was present as one molecule for every 91 nm2 in the cytoplasmic membrane. All three proteins were rapidly reduced to the same relative extent when suspensions of live bacteria were mixed with different concentrations of ferrous ions at pH 1.5. The subsequent molecular oxygen-dependent oxidation of the multicenter respiratory chain occurred with a single macroscopic rate constant, regardless of the proteins' in vitro redox potentials or their putative positions in the aerobic iron respiratory chain. The crowded electron transport proteins in the periplasm of the organism constituted an electron conductive medium where the network of protein interactions functioned in a concerted fashion as a single ensemble with a standard reduction potential of 650 mV. The appearance of product ferric ions was correlated with the reduction levels of the periplasmic electron transfer proteins; the limiting first-order catalytic rate constant for aerobic respiration on iron was 7,400 s−1. The ability to conduct direct spectrophotometric studies under noninvasive physiological conditions represents a new and powerful approach to examine the extent and rates of biological events in situ without disrupting the complexity of the live cellular environment. PMID:26041781

  20. The mitochondrial respiratory chain of the secondary green alga Euglena gracilis shares many additional subunits with parasitic Trypanosomatidae.

    Science.gov (United States)

    Perez, Emilie; Lapaille, Marie; Degand, Hervé; Cilibrasi, Laura; Villavicencio-Queijeiro, Alexa; Morsomme, Pierre; González-Halphen, Diego; Field, Mark C; Remacle, Claire; Baurain, Denis; Cardol, Pierre

    2014-11-01

    The mitochondrion is an essential organelle for the production of cellular ATP in most eukaryotic cells. It is extensively studied, including in parasitic organisms such as trypanosomes, as a potential therapeutic target. Recently, numerous additional subunits of the respiratory-chain complexes have been described in Trypanosoma brucei and Trypanosoma cruzi. Since these subunits had apparently no counterparts in other organisms, they were interpreted as potentially associated with the parasitic trypanosome lifestyle. Here we used two complementary approaches to characterise the subunit composition of respiratory complexes in Euglena gracilis, a non-parasitic secondary green alga related to trypanosomes. First, we developed a phylogenetic pipeline aimed at mining sequence databases for identifying homologues to known respiratory-complex subunits with high confidence. Second, we used MS/MS proteomics after two-dimensional separation of the respiratory complexes by Blue Native- and SDS-PAGE both to confirm in silico predictions and to identify further additional subunits. Altogether, we identified 41 subunits that are restricted to E. gracilis, T. brucei and T. cruzi, along with 48 classical subunits described in other eukaryotes (i.e. plants, mammals and fungi). This moreover demonstrates that at least half of the subunits recently reported in T. brucei and T. cruzi are actually not specific to Trypanosomatidae, but extend at least to other Euglenozoa, and that their origin and function are thus not specifically associated with the parasitic lifestyle. Furthermore, preliminary biochemical analyses suggest that some of these additional subunits underlie the peculiarities of the respiratory chain observed in Euglenozoa. Copyright © 2014 Elsevier B.V. All rights reserved.

  1. [Oral treatment of vitamin B12 deficiency in subacute combined degeneration].

    Science.gov (United States)

    Wellmer, J; Sturm, K-U; Herrmann, W; Hoever, J; Klockgether, T; Linnebank, M

    2006-10-01

    Vitamin B12 deficiency due to malnutrition or malabsorption may lead to pernicious anemia and neurological disorders. Although randomized prospective studies have shown that pernicious anemia can be safely treated with oral vitamin B12 even in the absence of intrinsic factor, it is still common practice to treat patients with neurological symptoms with intramuscular cyancobalamin injections. We report the successful oral treatment of subacute combined degeneration of the spinal cord in a 24-year-old woman closely monitored clinically with MRI and plasma levels of vitamin B12, homocysteine, and methylmalonic acid. We suggest monitored oral substitution therapy as first-line therapy for neurological disorders related to vitamin B12 deficiency.

  2. Reducing iron deficiency anemia in Bolivian school children: calcium and iron combined versus iron supplementation alone.

    Science.gov (United States)

    Miranda, Melissa; Olivares, Manuel; Brito, Alex; Pizarro, Fernando

    2014-01-01

    The aim of this study was to determine the effect of combined calcium and iron versus single iron supplementation on iron status in Bolivian schoolchildren. Children ages 6 to 10 y old (N = 195), were randomly assigned to receive either 700 mg Ca (as calcium carbonate) plus 30 mg Fe (as ferrous sulfate) (Ca + Fe group) or 30 mg Fe (as ferrous sulfate) (Fe group). The doses were administered daily, from Monday to Friday, between meals at school over 3 mo. Iron status was assessed at baseline and after intervention. Additionally, overall nutritional status was assessed by anthropometry and an estimation of dietary intake. At baseline, the prevalence of anemia in the Ca + Fe group and the Fe group were 15% and 21.5%, respectively. After 3 mo follow-up, the prevalence of iron deficiency anemia dropped significantly (P iron deficiency anemia in Bolivian school children. Copyright © 2014 Elsevier Inc. All rights reserved.

  3. Myelofibrosis in severe combined immunodeficiency due to vitamin D deficiency rickets.

    Science.gov (United States)

    al-Eissa, Y A; al-Mashhadani, S A

    1994-01-01

    An infant with severe combined immunodeficiency is described in whom a refractory anemia and thrombocytopenia developed after the age of 6 months, associated with poor growth and frequent episodes of upper respiratory tract infections and diarrhea. He required frequent blood and platelet transfusions. Bone marrow biopsy provided evidence that the anemia and thrombocytopenia were the results of myelofibrosis which was secondary to vitamin D deficiency. Therapy with 1,25-dihydroxycholecalciferol resulted in resolution of the hematologic and skeletal abnormalities, but he remained susceptible to recurrent serious infections and died at the age of 13 months.

  4. Combined deficiency of iron and (n-3) fatty acids in male rats disrupts brain monoamine metabolism and produces greater memory deficits than iron deficiency or (n-3) fatty acid deficiency alone1-3

    OpenAIRE

    Baumgartner, Jeannine; Smuts, Cornelius M; Malan, Linda; Arnold, Myrtha; Yee, Benjamin K

    2012-01-01

    Deficiencies of iron (Fe) (ID) and (n-3) fatty acids (FA) [(n-3)FAD] may impair brain development and function through shared mechanisms. However, little is known about the potential interactions between these 2 common deficiencies. We studied the effects of ID and (n-3)FAD, alone and in combination, on brain monoamine pathways (by measuring monoamines and related gene expression) and spatial working and reference memory (by Morris water maze testing). Using a 2 × 2 design, male rats were fed...

  5. Synthesis and biological activities of the respiratory chain inhibitor aurachin D and new ring versus chain analogues

    Directory of Open Access Journals (Sweden)

    Xu-Wen Li

    2013-07-01

    Full Text Available Aurachins are myxobacterial 3-farnesyl-4(1H-quinolone derived compounds initially described as respiratory chain inhibitors, more specifically as inhibitors of various cytochrome complexes. They are also known as potent antibiotic compounds. We describe herein the first synthesis of aurachin D through a key Conrad–Limpach reaction. The same strategy was used to reach some ring as opposed to chain analogues, allowing for the description of structure–activity relationships. Biological screening of the analogues showed antiparasitic, cytotoxic, antibacterial and antifungal activities, and depletion of the mitochondrial membrane potential. The strongest activity was found on Plasmodium falciparum with a selectivity index of 345, compared to Vero cells, for the natural product and its geranyl analogue. The loss of mitochondrial membrane potential induced by aurachins in human U-2 OS osteosarcoma cells was studied, showing the best activity for aurachin D and a naphthalene analogue, yet without totally explaining the observed cytotoxic activity of the compounds. Finally, a synthetic entry is given to the complete carboheterocyclic core of aurachin H through the N-oxidation/epoxidation of aurachin D and a shorter chain analogue, followed by subsequent biomimetic cyclization.

  6. Early Infantile Epileptic Encephalopathy in an STXBP1 Patient with Lactic Acidemia and Normal Mitochondrial Respiratory Chain Function.

    Science.gov (United States)

    Li, Dong; Bhoj, Elizabeth; McCormick, Elizabeth; Wang, Fengxiang; Snyder, James; Wang, Tiancheng; Zhao, Yan; Kim, Cecilia; Chiavacci, Rosetta; Tian, Lifeng; Falk, Marni J; Hakonarson, Hakon

    2016-01-01

    A wide range of clinical findings have been associated with mutations in Syntaxin Binding Protein 1 (STXBP1), including multiple forms of epilepsy, nonsyndromic intellectual disability, and movement disorders. STXBP1 mutations have recently been associated with mitochondrial pathology, although it remains unclear if this phenotype is a part of the core feature for this gene disorder. We report a 7-year-old boy who presented for diagnostic evaluation of intractable epilepsy, episodic ataxia, resting tremor, and speech regression following a period of apparently normal early development. Mild lactic acidemia was detected on one occasion at the time of an intercurrent illness. Due to the concern for mitochondrial disease, ophthalmologic evaluation was performed that revealed bilateral midperiphery pigmentary mottling. Optical coherence tomography (OCT) testing demonstrated a bilaterally thickened ganglion cell layer in the perifovea. Skeletal muscle biopsy analysis showed no mitochondrial abnormalities or respiratory chain dysfunction. Exome sequencing identified a de novo c.1651C>T (p.R551C) mutation in STXBP1. Although mitochondrial dysfunction has been reported in some individuals, our proband had only mild lactic acidemia and no skeletal muscle tissue evidence of mitochondrial disease pathology. Thus, mitochondrial dysfunction is not an obligate feature of STXBP1 disease.

  7. Targeting the Mitochondrial Respiratory Chain of Cryptococcus through Antifungal Chemosensitization: A Model for Control of Non-Fermentative Pathogens

    Directory of Open Access Journals (Sweden)

    Kathleen L. Chan

    2013-07-01

    Full Text Available Enhanced control of species of Cryptococcus, non-fermentative yeast pathogens, was achieved by chemosensitization through co-application of certain compounds with a conventional antimicrobial drug. The species of Cryptococcus tested showed higher sensitivity to mitochondrial respiratory chain (MRC inhibition compared to species of Candida. This higher sensitivity results from the inability of Cryptococcus to generate cellular energy through fermentation. To heighten disruption of cellular MRC, octyl gallate (OG or 2,3-dihydroxybenzaldehyde (2,3-DHBA, phenolic compounds inhibiting mitochondrial functions, were selected as chemosensitizers to pyraclostrobin (PCS; an inhibitor of complex III of MRC. The cryptococci were more susceptible to the chemosensitization (i.e., PCS + OG or 2,3-DHBA than the Candida with all Cryptococcus strains tested being sensitive to this chemosensitization. Alternatively, only few of the Candida strains showed sensitivity. OG possessed higher chemosensitizing potency than 2,3-DHBA, where the concentration of OG required with the drug to achieve chemosensitizing synergism was much lower than that required of 2,3-DHBA. Bioassays with gene deletion mutants of the model yeast Saccharomyces cerevisiae showed that OG or 2,3-DHBA affect different cellular targets. These assays revealed mitochondrial superoxide dismutase or glutathione homeostasis plays a relatively greater role in fungal tolerance to 2,3-DHBA or OG, respectively. These findings show that application of chemosensitizing compounds that augment MRC debilitation is a promising strategy to antifungal control against yeast pathogens.

  8. Early Infantile Epileptic Encephalopathy in an STXBP1 Patient with Lactic Acidemia and Normal Mitochondrial Respiratory Chain Function

    Directory of Open Access Journals (Sweden)

    Dong Li

    2016-01-01

    Full Text Available A wide range of clinical findings have been associated with mutations in Syntaxin Binding Protein 1 (STXBP1, including multiple forms of epilepsy, nonsyndromic intellectual disability, and movement disorders. STXBP1 mutations have recently been associated with mitochondrial pathology, although it remains unclear if this phenotype is a part of the core feature for this gene disorder. We report a 7-year-old boy who presented for diagnostic evaluation of intractable epilepsy, episodic ataxia, resting tremor, and speech regression following a period of apparently normal early development. Mild lactic acidemia was detected on one occasion at the time of an intercurrent illness. Due to the concern for mitochondrial disease, ophthalmologic evaluation was performed that revealed bilateral midperiphery pigmentary mottling. Optical coherence tomography (OCT testing demonstrated a bilaterally thickened ganglion cell layer in the perifovea. Skeletal muscle biopsy analysis showed no mitochondrial abnormalities or respiratory chain dysfunction. Exome sequencing identified a de novo c.1651C>T (p.R551C mutation in STXBP1. Although mitochondrial dysfunction has been reported in some individuals, our proband had only mild lactic acidemia and no skeletal muscle tissue evidence of mitochondrial disease pathology. Thus, mitochondrial dysfunction is not an obligate feature of STXBP1 disease.

  9. Dedicator of cytokinesis 8 mutation related combined immune deficiency: A single centre experience from India

    Directory of Open Access Journals (Sweden)

    Dhwanee Thakkar

    2017-10-01

    Full Text Available The Dedicator of cytokinesis 8 (DOCK8 related combined immune deficiency is a recently discovered entity which differs from the classic STAT3 associated autosomal dominant hyper-IgE syndrome with respect to the genetic origin and the clinical manifestations. It is characterised by increased risk of autoimmunity, malignancy and neurological complications in addition to increased risk of recurrent cutaneous, sinopulmonary and gastrointestinal infections. We report a series 11 children from three families suffering from DOCK8 related combined immunodeficiency. Out of 11 children only 5 were alive at diagnosis and rest 6 were siblings who had died of similar complaints. Among the 5 children only one underwent allogeneic haploidentical stem cell transplant (SCT from his mother but died before engraftment due to infection. Other 4 are alive without SCT but have multiple co-morbidities. A constellation of cutaneous lesions, recurrent sinopulmonary & gastro intestinal infections and allergic manifestations in a child who may have a similar family history should arouse a suspicion of combined immunodeficiency associated with DOCK8 mutation. Early diagnosis in such children can expedite the appropriate management with SCT. Keywords: Combined immunodeficiency, DOCK8, Children

  10. Growth without growth hormone in combined pituitary hormone deficiency caused by pituitary stalk interruption syndrome

    Directory of Open Access Journals (Sweden)

    Sang Soo Lee

    2017-03-01

    Full Text Available Growth hormone (GH is an essential element for normal growth. However, reports of normal growth without GH have been made in patients who have undergone brain surgery for craniopharyngioma. Normal growth without GH can be explained by hyperinsulinemia, hyperprolactinemia, elevated leptin levels, and GH variants; however, its exact mechanism has not been elucidated yet. We diagnosed a female patient aged 13 with combined pituitary hormone deficiency (CPHD caused by pituitary stalk interruption syndrome (PSIS. The patient has experienced recurrent hypoglycemic seizures since birth, but reached the height of 160 cm at the age of 13, showing normal growth. She grew another 8 cm for 3 years after the diagnosis, and she reached her final adult height of 168 cm which was greater than the midparental height, at the age of 16. The patient's blood GH and insulin-like growth factor-I levels were consistently subnormal, although her insulin levels were normal. Her physical examination conducted at the age of 15 showed truncal obesity, dyslipidemia, and osteoporosis, which are metabolic features of GH deficiency (GHD. Herein, we report a case in which a PSIS-induced CPHD patient attained her final height above mid parental height despite a severe GHD.

  11. Neonatal Screening for Severe Combined Immune Deficiency in Russia: Glorious Future or Tomorrow’s Reality?

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    Svetlana S. Deryabina

    2017-01-01

    Full Text Available Mass screening of newborns in Russia for five hereditary diseases does not meet the requirements of the world community for the neonatal screening program. Success in the development of laboratory diagnostic technologies and active introduction of achievements in genetics and molecular biology into medical practice allow for the revision of the list of nosologies included in the national neonatal screening program by replacing the disease or adding new nosologies. The article discusses the possibility of including genetic testing for severe combined immune deficiency in the Newborn Screening Program in Russia. The results from a retrospective study of markers of naive T- and B-lymphocytes (TREC and KREC in the group of children with immuno-dependent pathology developed in the first year of life are discussed.

  12. Affection of the Respiratory Muscles in Combined Complex I and IV Deficiency.

    Science.gov (United States)

    Finsterer, Josef; Rauschka, Helmut; Segal, Liane; Kovacs, Gabor G; Rolinski, Boris

    2017-01-01

    Combined complex I+IV deficiency has rarely been reported to manifest with the involvement of the respiratory muscles. A 45y male was admitted for hypercapnia due to muscular respiratory insufficiency. He required intubation and mechanical ventilation. He had a previous history of ophthalmoparesis since age 6y, ptosis since age 23y, and anterocollis since at least age 40y. Muscle biopsy from the right deltoid muscle at age 41y was indicative of mitochondrial myopathy. Biochemical investigations revealed a combined complex I+IV defect. Respiratory insufficiency was attributed to mitochondrial myopathy affecting not only the extra-ocular and the axial muscles but also the shoulder girdle and respiratory muscles. In addition to myopathy, he had mitochondrial neuropathy, abnormal EEG, and elevated CSF-protein. Possibly, this is why a single cycle of immunoglobulins was somehow beneficial. For muscular respiratory insufficiency he required tracheostomy and was scheduled for long-term intermittent positive pressure ventilation. Mitochondrial myopathy due to a combined complex I+IV defect with predominant affection of the extra-ocular muscles may progress to involvement of the limb-girdle, axial and respiratory muscles resulting in muscular respiratory insufficiency. In patients with mitochondrial myopathy, neuropathy and elevated cerebrospinal fluid protein, immunoglobulins may be beneficial even for respiratory functions.

  13. Administration of Harmine and Imipramine Alters Creatine Kinase and Mitochondrial Respiratory Chain Activities in the Rat Brain

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    Gislaine Z. Réus

    2012-01-01

    Full Text Available The present study evaluated mitochondrial respiratory chain and creatine kinase activities after administration of harmine (5, 10, and 15 mg/kg and imipramine (10, 20, and 30 mg/kg in rat brain. After acute treatment occurred an increase of creatine kinase in the prefrontal with imipramine (20 and 30 mg/kg and harmine in all doses, in the striatum with imipramine (20 and 30 mg/kg and harmine (5 and 10 mg/kg; harmine (15 mg/kg decreased creatine kinase. In the chronic treatment occurred an increase of creatine kinase with imipramine (20 mg/kg, harmine (5 mg/kg in the prefrontal with imipramine (20 and 30 mg/kg and harmine (5 and 10 mg/kg in the striatum. In the acute treatment, the complex I increased in the prefrontal with harmine (15 mg/kg and in the striatum with harmine (10 mg/kg; the complex II decreased with imipramine (20 and 30 mg/kg in the striatum; the complex IV increased with imipramine (30 mg/kg in the striatum. In the chronic treatment, the complex I increased with harmine (5 mg/kg in the prefrontal; the complex II increased with imipramine (20 mg/kg in the prefrontal; the complex IV increased with harmine (5 mg/kg in the striatum. Finally, these findings further support the hypothesis that harmine and imipramine could be involved in mitochondrial function.

  14. Possible role of mtDNA depletion and respiratory chain defects in aristolochic acid I-induced acute nephrotoxicity

    Energy Technology Data Exchange (ETDEWEB)

    Jiang, Zhenzhou, E-mail: jiangcpu@yahoo.com.cn; Bao, Qingli, E-mail: bao_ql@126.com; Sun, Lixin, E-mail: slxcpu@126.com; Huang, Xin, E-mail: huangxinhx66@sohu.com; Wang, Tao, E-mail: wangtao1331@126.com; Zhang, Shuang, E-mail: cat921@sina.com; Li, Han, E-mail: hapo1101@163.com; Zhang, Luyong, E-mail: lyzhang@cpu.edu.cn

    2013-01-15

    This report describes an investigation of the pathological mechanism of acute renal failure caused by toxic tubular necrosis after treatment with aristolochic acid I (AAI) in Sprague–Dawley (SD) rats. The rats were gavaged with AAI at 0, 5, 20, or 80 mg/kg/day for 7 days. The pathologic examination of the kidneys showed severe acute tubular degenerative changes primarily affecting the proximal tubules. Supporting these results, we detected significantly increased concentrations of blood urea nitrogen (BUN) and creatinine (Cr) in the rats treated with AAI, indicating damage to the kidneys. Ultrastructural examination showed that proximal tubular mitochondria were extremely enlarged and dysmorphic with loss and disorientation of their cristae. Mitochondrial function analysis revealed that the two indicators for mitochondrial energy metabolism, the respiratory control ratio (RCR) and ATP content, were reduced in a dose-dependent manner after AAI treatment. The RCR in the presence of substrates for complex I was reduced more significantly than in the presence of substrates for complex II. In additional experiments, the activity of respiratory complex I, which is partly encoded by mitochondrial DNA (mtDNA), was more significantly impaired than that of respiratory complex II, which is completely encoded by nuclear DNA (nDNA). A real-time PCR assay revealed a marked reduction of mtDNA in the kidneys treated with AAI. Taken together, these results suggested that mtDNA depletion and respiratory chain defects play critical roles in the pathogenesis of kidney injury induced by AAI, and that the same processes might contribute to aristolochic acid-induced nephrotoxicity in humans. -- Highlights: ► AAI-induced acute renal failure in rats and the proximal tubule was the target. ► Tubular mitochondria were morphologically aberrant in ultrastructural examination. ► AAI impair mitochondrial bioenergetic function and mtDNA replication.

  15. EFFECTS OF AMANTADINE ON BEHAVIOR, RESPIRATORY CHAIN ENZYMES AND CREATINE KINASE IN AN ANIMAL MODEL OF SCHIZOPHRENIA

    Directory of Open Access Journals (Sweden)

    David de Lucena

    2013-03-01

    Full Text Available Introduction: Glutamate dysregulation may be involved in the pathophysiology of schizophrenia, and NMDA antagonists seem to be effective in its treatment. We evaluated the efficacy of amantadine (AMA in preventing ketamine (KET-induced effects in an animal model of schizophrenia. Methods: Adult Wistar rats received 10 mg/kg AMA for 10 days, followed by 7 days of 25 mg/kg KET ip. Thirty minutes after the last injection, rats were placed in an open-field apparatus for 60 minutes and killed by decapitation afterwards. Amygdala, hippocampus, prefrontal cortex and striatum were isolated and analyzed for creatine kinase (CK and respiratory chain enzyme activities. Results: KET increased crossings and reduced grooming, which was not prevented by AMA. KET also increased stereotypic movements, which was partially prevented by AMA. As for CK activity, KET increased it in the prefrontal cortex, striatum and amygdala, and AMA prevented it only in prefrontal cortex and striatum. The activity of complex I was not altered by KET, however, AMA+KET increased it in the striatum and amygdala. KET increased the activity of complex II in the striatum as well, whereas AMA+KET increased it in hippocampus, prefrontal cortex, and striatum. KET did not alter complex I-III activity, whereas AMA+KET increased it in hippocampus and amygdala. AMA+KET also increased complex IV activity in hippocampus and striatum, whereas KET had no effect on this activity. Conclusion: AMA did not prevent most of KET-induced alterations. New animal models should be employed in the study of AMA as a potential novel drug for schizophrenia.

  16. Bactericidal peptidoglycan recognition protein induces oxidative stress in Escherichia coli through a block in respiratory chain and increase in central carbon catabolism.

    Science.gov (United States)

    Kashyap, Des R; Kuzma, Marcin; Kowalczyk, Dominik A; Gupta, Dipika; Dziarski, Roman

    2017-09-01

    Mammalian Peptidoglycan Recognition Proteins (PGRPs) kill both Gram-positive and Gram-negative bacteria through simultaneous induction of oxidative, thiol and metal stress responses in bacteria. However, metabolic pathways through which PGRPs induce these bactericidal stress responses are unknown. We screened Keio collection of Escherichia coli deletion mutants and revealed that deleting genes for respiratory chain flavoproteins or for tricarboxylic acid (TCA) cycle resulted in increased resistance of E. coli to PGRP killing. PGRP-induced killing depended on the production of hydrogen peroxide, which required increased supply of NADH for respiratory chain oxidoreductases from central carbon catabolism (glycolysis and TCA cycle), and was controlled by cAMP-Crp. Bactericidal PGRP induced a rapid decrease in respiration, which suggested that the main source of increased production of hydrogen peroxide was a block in respiratory chain and diversion of electrons from NADH oxidoreductases to oxygen. CpxRA two-component system was a negative regulator of PGRP-induced oxidative stress. By contrast, PGRP-induced thiol stress (depletion of thiols) and metal stress (increase in intracellular free Zn2+ through influx of extracellular Zn2+ ) were mostly independent of oxidative stress. Thus, manipulating pathways that induce oxidative, thiol and metal stress in bacteria could be a useful strategy to design new approaches to antibacterial therapy. © 2017 John Wiley & Sons Ltd.

  17. Activity of the Respiratory Chain Enzymes of Blood Leucocytes’ Mitochondria Under the Conditions of Toxic Hepatitis Induced Against the Background Alimentary Deprivation of Protein

    Directory of Open Access Journals (Sweden)

    O.N. Voloshchuk

    2015-12-01

    Full Text Available Full functioning of the leucocytes’ energy supply system is one of the essential factors for the immune surveillance system effective work. The pivotal enzymes of the leucocytes’ energy biotransformation system are NADH-ubiquitin reductase, a marker of the Complex I of respiratory chain activity, and succinate dehydrogenase, key enzyme of the Complex II of respiratory chain. The aim of research – to study the NADH-ubiquitin reductase and succinate dehydrogenase activity of the blood leucocytes’ mitochondria under the conditions of toxic hepatitis induced against the background alimentary deprivation of protein. It is shown, that under the conditions of acetaminophen-induced hepatitis a reduction of the NADH-ubiquitin reductase enzymatic activity is observed on the background activation of the succinate-dependent way of the mitochondrial oxidation. Conclusion was made that alimentary deprivation or protein is a factor, aggravating the misbalance of the energy biotransformation system in the leucocytes of rats with toxic hepatitis. Established activity changes of the leucocytes’ mitochondria respiratory chain key enzymes may be considered as one of the mechanisms, directed on the maintenance of leucocytes energy supply on a level, sufficient for their functioning. Research results may be used for the biochemical rationale of the therapeutic approaches to the elimination and correction of the leucocytes’ energy metabolism disturbances consequences under the conditions of acetaminophen-induced hepatitis, aggravated by the alimentary protein deprivation.

  18. Development of gene therapy: potential in severe combined immunodeficiency due to adenosine deaminase deficiency

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    Claudia A Montiel-Equihua

    2009-12-01

    Full Text Available Claudia A Montiel-Equihua, Adrian J Thrasher, H Bobby GasparCentre for Immunodeficiency, Molecular Immunology Unit, UCL Institute of Child Health, London, UKAbstract: The history of stem cell gene therapy is strongly linked to the development of gene therapy for severe combined immunodeficiencies (SCID and especially adenosine deaminase (ADA-deficient SCID. Here we discuss the developments achieved in over two decades of clinical and laboratory research that led to the establishment of a protocol for the autologous transplant of retroviral vector-mediated gene-modified hematopoietic stem cells, which has proved to be both successful and, to date, safe. Patients in trials in three different countries have shown long-term immunological and metabolic correction. Nevertheless, improvements to the safety profile of viral vectors are underway and will undoubtedly reinforce the position of stem cell gene therapy as a treatment option for ADA-SCID.Keywords: adenosine deaminase, severe combined immunodeficiency, gene therapy, hematopoietic stem cell, retrovirus, clinical trial

  19. Left main coronary artery thrombus resulting from combined protein C and S deficiency.

    Science.gov (United States)

    Sayin, Muhammet R; Akpinar, Ibrahim; Karabag, Turgut; Aydin, Mustafa; Dogan, Sait M; Cil, Cem

    2012-01-01

    Inherited hypercoagulopathies such as protein C and S deficiency usually lead to the formation of venous thrombi in clinical practice; however, they rarely lead to arterial thrombosis. It has been demonstrated that both protein C and S deficiency may lead to myocardial infarctions. However, our literature review revealed no reports of left main coronary artery thrombi caused by protein C and S deficiency. This paper presents a case of a left main coronary artery thrombus resulting from protein C and S deficiency in a young patient with normal coronary arteries.

  20. Analysis of mitochondrial DNA sequences in patients with isolated or combined oxidative phosphorylation system deficiency.

    NARCIS (Netherlands)

    Hinttala, R.; Smeets, R.; Moilanen, J.S.; Ugalde, C.; Uusimaa, J.; Smeitink, J.A.M.; Majamaa, K.

    2006-01-01

    BACKGROUND: Enzyme deficiencies of the oxidative phosphorylation (OXPHOS) system may be caused by mutations in the mitochondrial DNA (mtDNA) or in the nuclear DNA. OBJECTIVE: To analyse the sequences of the mtDNA coding region in 25 patients with OXPHOS system deficiency to identify the underlying

  1. Metabolome and proteome profiling of complex I deficiency induced by rotenone.

    Science.gov (United States)

    Gielisch, Ina; Meierhofer, David

    2015-01-02

    Complex I (CI; NADH dehydrogenase) deficiency causes mitochondrial diseases, including Leigh syndrome. A variety of clinical symptoms of CI deficiency are known, including neurodegeneration. Here, we report an integrative study combining liquid chromatography-mass spectrometry (LC-MS)-based metabolome and proteome profiling in CI deficient HeLa cells. We report a rapid LC-MS-based method for the relative quantification of targeted metabolome profiling with an additional layer of confidence by applying multiple reaction monitoring (MRM) ion ratios for further identity confirmation and robustness. The proteome was analyzed by label-free quantification (LFQ). More than 6000 protein groups were identified. Pathway and network analyses revealed that the respiratory chain was highly deregulated, with metabolites such as FMN, FAD, NAD(+), and ADP, direct players of the OXPHOS system, and metabolites of the TCA cycle decreased up to 100-fold. Synthesis of functional iron-sulfur clusters, which are of central importance for the electron transfer chain, and degradation products like bilirubin were also significantly reduced. Glutathione metabolism on the pathway level, as well as individual metabolite components such as NADPH, glutathione (GSH), and oxidized glutathione (GSSG), was downregulated. Overall, metabolome and proteome profiles in CI deficient cells correlated well, supporting our integrated approach.

  2. [Effects of carnitine on respiratory chain and metabolism of oxygen radical in mitochondria of skeletal muscle after exhaustive running in training rat].

    Science.gov (United States)

    Li, Jie; Peng, Li-Na

    2013-12-25

    The aim of the present study was to investigate the effect of carnitine on function of respiratory chain and metabolism of oxygen radical in mitochondria of skeletal muscle after exhaustive running in training rats. Forty male Wistar rats were randomly divided into 4 groups (n = 10): control, carnitine, training and training + carnitine groups. The training and training + carnitine groups received 6-week treadmill training, whereas carnitine and training + carnitine groups were administered intragastrically with carnitine (300 mg/kg per day, 6 d/week) for 6 weeks. After exhaustive running, all the rats from 4 groups were sacrificed to obtain quadriceps muscles samples, and muscle mitochondria were extracted by differential centrifugation. Spectrophotometric analysis was used to evaluate activities of respiratory chain complexes (RCC) I-IV, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and the content of malondialdehyde (MDA) in the skeletal muscle mitochondria. The results showed that, compared with the control group, the carnitine group exhibited increased RCCI and RCCIII activities (P carnitine group exhibited increased RCCI, RCCIII and RCCIV activities (P carnitine group was higher than that in training group (P carnitine, training and training + carnitine groups showed increased SOD activities ( P carnitine and training + carnitine groups showed increased GSH-Px activities ( P carnitine, training and training + carnitine groups showed increased MDA contents (P carnitine group were higher than those in training group (P carnitine group was higher than that in the carnitine and training groups (P carnitine can increase function of respiratory chain, antioxidation and lipid peroxidation tolerance capacity in skeletal muscle mitochondria, and the improving effects of training and carnitine are synergistic.

  3. [Effects of carnitine on respiratory chain and metabolism of oxygen radical in mitochondria of liver after exhaustive running in training rat].

    Science.gov (United States)

    Li, Jie; Chen, Li

    2012-08-25

    The aim of the present study was to investigate the effect of carnitine on cellular respiratory chain and metabolism of oxygen radical in mitochondria of liver after exhaustive running in training rats. Forty male Wistar rats were randomly divided into 4 groups (n = 10): control, carnitine, training and training+carnitine groups. The training and training+carnitine groups received 6-week treadmill training, whereas carnitine and training+carnitine groups were administrated intragastrically with carnitine (300 mg/kg per d) for 6 weeks. After exhaustive running, all the groups were sacrificed to obtain liver samples, and liver mitochondria were extracted by differential centrifugation. Spectrophotometric analysis was used to evaluate activities of respiratory chain complexes (RCC) I-IV, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and the content of malondialdehyde (MDA) in the liver mitochondria. The results showed that, compared with the control group, the carnitine group exhibited increased RCCIV activity (P carnitine group showed increased RCCI-IV activities (P carnitine group were higher than those in the carnitine and training groups (P carnitine group showed increased SOD activity (P carnitine, training and training+carnitine groups showed increased GSH-Px activities (P carnitine groups showed decreased MDA contents (P carnitine group showed increased GSH-Px activity compared to that in the carnitine group (P carnitine group was higher than those in the carnitine and training groups (P carnitine group was lower than those in the carnitine and training groups (P carnitine can increase the function of respiratory chain and antioxidant capacity in liver mitochondria, and the improving effects of training and carnitine can be synergistic.

  4. Combined Iron Deficiency and Low Aerobic Fitness Doubly Burden Academic Performance among Women Attending University.

    Science.gov (United States)

    Scott, Samuel P; De Souza, Mary Jane; Koehler, Karsten; Murray-Kolb, Laura E

    2017-01-01

    Academic success is a key determinant of future prospects for students. Cognitive functioning has been related to nutritional and physical factors. Here, we focus on iron status and aerobic fitness in young-adult female students given the high rate of iron deficiency and declines in fitness reported in this population. We sought to explore the combined effects of iron status and fitness on academic success and to determine whether these associations are mediated by cognitive performance. Women (n = 105) aged 18-35 y were recruited for this cross-sectional study. Data were obtained for iron biomarkers, peak oxygen uptake (VO2peak), grade point average (GPA), performance on computerized attention and memory tasks, and motivation and parental occupation. We compared the GPA of groups 1) with low compared with normal iron status, 2) among different fitness levels, and 3) by using a combined iron status and fitness designation. Mediation analysis was applied to determine whether iron status and VO2peak influence GPA through attentional and mnemonic function. After controlling for age, parental occupation, and motivation, GPA was higher in women with normal compared with low ferritin (3.66 ± 0.06 compared with 3.39 ± 0.06; P = 0.01). In analyses of combined effects of iron status and fitness, GPA was higher in women with normal ferritin and higher fitness (3.70 ± 0.08) than in those with 1) low ferritin and lower fitness (3.36 ± 0.08; P = 0.02) and 2) low ferritin and higher fitness (3.44 ± 0.09; P = 0.04). Path analysis revealed that working memory mediated the association between VO2peak and GPA. Low iron stores and low aerobic fitness may prevent female college students from achieving their full academic potential. Investigators should explore whether integrated lifestyle interventions targeting nutritional status and fitness can benefit cognitive function, academic success, and postgraduate prospects. © 2017 American Society for Nutrition.

  5. Plasmodium falciparum clearance with artemisinin-based combination therapy (ACT in patients with glucose-6-phosphate dehydrogenase deficiency in Mali

    Directory of Open Access Journals (Sweden)

    Djimde Abdoulaye

    2010-11-01

    Full Text Available Abstract Background Artemisinin-based combination therapy (ACT is currently the most effective medicine for the treatment of uncomplicated malaria. Artemisinin has previously been shown to increase the clearance of Plasmodium falciparum in malaria patients with haemoglobin E trait, but it did not increase parasite inhibition in an in vitro study using haemoglobin AS erythrocytes. The current study describes the efficacy of artemisinin derivatives on P. falciparum clearance in patients with glucose-6-phosphate dehydrogenase deficiency (G6PD, a haemoglobin enzyme deficiency, not yet studied in the same context, but nonetheless is a common in malaria endemic areas, associated with host protection against uncomplicated and severe malaria. The impact of G6PD deficiency on parasite clearance with ACT treatment was compared between G6PD-deficient patients and G6PD-normal group. Methods Blood samples from children and adults participants (1 to 70 years old with uncomplicated P. falciparum malaria residing in Kambila, Mali were analysed. Study participants were randomly assigned to receive either artemether-lumefantrine (Coartem® or artesunate plus mefloquine (Artequin™. A restriction-fragment length polymorphism analysis of PCR-amplified DNA samples was used to identify the (A- allele of the gene mutation responsible for G6PD deficiency (G6PD*A-. 470 blood samples were thus analysed and of these, DNA was extracted from 315 samples using the QIAamp kit for PCR to identify the G6PD*A- gene. Results The DNA amplified from 315 samples using PCR showed that G6PD*A- deficiency was present in 56 participants (17.8%. The distribution of the specific deficiency was 1%, 7% and, 9.8% respectively for homozygous, hemizygous, and heterozygous genotypes. Before treatment, the median parasitaemia and other baseline characteristics (mean haemoglobin, sex and age groups between G6PD deficiency (hemizygous, heterozygous, and homozygous and G6PD-normal participants

  6. Use of combined measures from capillary blood to assess iron deficiency in rural Kenyan children.

    Science.gov (United States)

    Shell-Duncan, Bettina; McDade, Thomas

    2004-02-01

    Community-based surveys of iron deficiency (ID) require simple, accurate methods that can be used in remote areas. The objective of this study was to assess iron status in rural Kenya using "field-friendly" methods for capillary blood, including an improved dried blood spot assay for transferrin receptor (TfR). A single finger stick was used to obtain capillary blood from 275 school-age children. Whole blood was applied directly to filter paper, dried, and later analyzed for TfR, as well as C-reactive protein (CRP), an acute-phase protein that serves as a general marker of inflammation. Capillary blood was also used to measure hemoglobin (Hb) concentration and the ratio of zinc protoporphyrin to heme (ZPP:H). The Hb concentration alone provides the lowest estimate of the prevalence of ID (8.0%). Because ZPP:H is reported to be elevated in the presence of inflammation, we constructed a preliminary diagnostic model based on elevated ZPP:H and normal CRP level, estimating the prevalence of ID at 25.9%. When TfR is added to a multiple criteria model (elevated ZPP:H in the absence of elevated CRP and/or elevated TfR level) the prevalence of ID is estimated to be 31.2%. This study demonstrates the diagnostic utility of combining TfR with other indexes of iron status, enabling the detection of ID in both the presence and absence of infection. Furthermore, this study is the first field application of TfR blood-spot methods, and it demonstrates their feasibility in remote field settings.

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

    Science.gov (United States)

    ... should be performed by a specialist at a hemophilia/bleeding disorders treatment centre . Care should be taken, particularly in newborns, to exclude causes of acquired vitamin K deficiency or exposure to certain medications. ...

  8. The first results of pilot project on combined preventive suplementation of iodine- and iron deficiency conditions in Tyumen region

    Directory of Open Access Journals (Sweden)

    G V Sharuho

    2010-12-01

    Full Text Available In 2008–2010 pilot project were realized in Tyumen region on combined preventive maintenance iodine deficiency and iron deficiency conditions, within the framework of which children from pilot of the territory got feeding, enriched premixes of the iodine and ferric while checking group has formed the children, getting monoprevention iodized salt. In study were examined 467 children. Frequency of the goiter on ultrasonography in pilot territory fell from 19.8 to 6.4%, in checking from 12.5 to 10.1%. In group teenager on background combined micronutrient preventive maintenance frequency tests ferritin less 15 mcg/l fell for 76 weeks in four times (p = 0.000, herewith average factors in 2010 above, than in 2008 (p = 0.114. In group teenager checking territory on background monoprevention frequency of the lowered tests ferritin more, than in group on background of the combined preventive maintenance in 2 times (p = 0.004, improvements for period of the study is not revealed.Dynamics indices of iodine deficiency conditions on background of the combined preventive maintenance and monoprevention confirms greater efficiency of the simultaneous using the products fortifications iodine and iron. Shown efficiency micronutrient preventive maintenances of the latent deficit ferric fortifications bread.

  9. Marked inhibition of Na+, K(+)- ATPase activity and the respiratory chain by phytanic acid in cerebellum from young rats: possible underlying mechanisms of cerebellar ataxia in Refsum disease.

    Science.gov (United States)

    Busanello, Estela Natacha Brandt; Zanatta, Ângela; Tonin, Anelise Miotti; Viegas, Carolina Maso; Vargas, Carmen Regla; Leipnitz, Guilhian; Ribeiro, César Augusto João; Wajner, Moacir

    2013-02-01

    Refsum disease is an autosomal recessive disorder of peroxisomal metabolism biochemically characterized by highly elevated concentrations of phytanic acid (Phyt) in a variety of tissues including the cerebellum. Reduction of plasma Phyt levels by dietary restriction intake ameliorates ataxia, a common clinical manifestation of this disorder, suggesting a neurotoxic role for this branched-chain fatty acid. Therefore, considering that the underlying mechanisms of cerebellum damage in Refsum disease are poorly known, in the present study we tested the effects of Phyt on important parameters of bioenergetics, such as the activities of the respiratory chain complexes I to IV, creatine kinase and Na(+), K(+)- ATPase in cerebellum preparations from young rats. The activities of complexes I, II, I-III and II-III and Na(+), K(+)- ATPase were markedly inhibited (65-85%) in a dose-dependent manner by Phyt. In contrast, creatine kinase and complex IV activities were not altered by this fatty acid. Therefore, it is presumed that impairment of the electron flow through the respiratory chain and inhibition of Na(+), K(+)- ATPase that is crucial for synaptic function may be involved in the pathophysiology of the cerebellar abnormalities manifested as ataxia in Refsum disease and in other peroxisomal disorders in which brain Phyt accumulates.

  10. Higher prevalence of metformin-induced vitamin B12 deficiency in sulfonylurea combination compared with insulin combination in patients with type 2 diabetes: a cross-sectional study.

    Science.gov (United States)

    Kang, Donghoon; Yun, Jae-Seung; Ko, Sun-Hye; Lim, Tae-Seok; Ahn, Yu-Bae; Park, Yong-Moon; Ko, Seung-Hyun

    2014-01-01

    Long-term and high-dose treatment with metformin is known to be associated with vitamin B12 deficiency in patients with type 2 diabetes. We investigated whether the prevalence of B12 deficiency was different in patients treated with different combination of hypoglycemic agents with metformin during the same time period. A total of 394 patients with type 2 diabetes treated with metformin and sulfonylurea (S+M group, n = 299) or metformin and insulin (I+M group, n = 95) were consecutively recruited. The vitamin B12 and folate levels were quantified using the chemiluminescent enzyme immunoassay. Vitamin B12 deficiency was defined as vitamin B12≤300 pg/mL without folate deficiency (folate>4 ng/mL). The mean age of and duration of diabetes in the subjects were 59.4±10.5 years and 12.2±6.7 years, respectively. The mean vitamin B12 level of the total population was 638.0±279.6 pg/mL. The mean serum B12 levels were significantly lower in the S+M group compared with the I+M group (600.0±266.5 vs. 757.7±287.6 pg/mL, Pvitamin B12 deficiency in the metformin-treated patients was significantly higher in the S+M group compared with the I+M group (17.4% vs. 4.2%, P = 0.001). After adjustment for various factors, such as age, sex, diabetic duration, duration or daily dose of metformin, diabetic complications, and presence of anemia, sulfonylurea use was a significant independent risk factor for B12 deficiency (OR = 4.74, 95% CI 1.41-15.99, P = 0.012). In conclusion, our study demonstrated that patients with type 2 diabetes who were treated with metformin combined with sulfonylurea require clinical attention for vitamin B12 deficiency and regular monitoring of their vitamin B12 levels.

  11. Higher prevalence of metformin-induced vitamin B12 deficiency in sulfonylurea combination compared with insulin combination in patients with type 2 diabetes: a cross-sectional study.

    Directory of Open Access Journals (Sweden)

    Donghoon Kang

    Full Text Available Long-term and high-dose treatment with metformin is known to be associated with vitamin B12 deficiency in patients with type 2 diabetes. We investigated whether the prevalence of B12 deficiency was different in patients treated with different combination of hypoglycemic agents with metformin during the same time period. A total of 394 patients with type 2 diabetes treated with metformin and sulfonylurea (S+M group, n = 299 or metformin and insulin (I+M group, n = 95 were consecutively recruited. The vitamin B12 and folate levels were quantified using the chemiluminescent enzyme immunoassay. Vitamin B12 deficiency was defined as vitamin B12≤300 pg/mL without folate deficiency (folate>4 ng/mL. The mean age of and duration of diabetes in the subjects were 59.4±10.5 years and 12.2±6.7 years, respectively. The mean vitamin B12 level of the total population was 638.0±279.6 pg/mL. The mean serum B12 levels were significantly lower in the S+M group compared with the I+M group (600.0±266.5 vs. 757.7±287.6 pg/mL, P<0.001. The prevalence of vitamin B12 deficiency in the metformin-treated patients was significantly higher in the S+M group compared with the I+M group (17.4% vs. 4.2%, P = 0.001. After adjustment for various factors, such as age, sex, diabetic duration, duration or daily dose of metformin, diabetic complications, and presence of anemia, sulfonylurea use was a significant independent risk factor for B12 deficiency (OR = 4.74, 95% CI 1.41-15.99, P = 0.012. In conclusion, our study demonstrated that patients with type 2 diabetes who were treated with metformin combined with sulfonylurea require clinical attention for vitamin B12 deficiency and regular monitoring of their vitamin B12 levels.

  12. Tissue-specific alterations in thyroid hormone homeostasis in combined Mct10 and Mct8 deficiency

    NARCIS (Netherlands)

    J. Müller (Julia); S. Mayerl (Steffen); T.J. Visser (Theo); V.M. Darras (Veerle); A. Boelen (Anita); L. Frappart (Lucien); L. Mariotta (Luca); F. Verrey; H. Heuer (Heike)

    2014-01-01

    textabstractThe monocarboxylate transporter Mct10 (Slc16a10; T-type amino acid transporter) facilitates the cellular transport of thyroid hormone (TH) and shows an overlapping expression with the wellestablished TH transporter Mct8. Because Mct8 deficiency is associated with distinct tissue-specific

  13. Tissue-specific alterations in thyroid hormone homeostasis in combined Mct10 and Mct8 deficiency

    NARCIS (Netherlands)

    Müller, Julia; Mayerl, Steffen; Visser, Theo J.; Darras, Veerle M.; Boelen, Anita; Frappart, Lucien; Mariotta, Luca; Verrey, Francois; Heuer, Heike

    2014-01-01

    The monocarboxylate transporter Mct10 (Slc16a10; T-type amino acid transporter) facilitates the cellular transport of thyroid hormone (TH) and shows an overlapping expression with the well-established TH transporter Mct8. Because Mct8 deficiency is associated with distinct tissue-specific

  14. Desmopressin acetate as a haemostatic elevator in individuals with combined deficiency of factors V and VIII: a clinical trial.

    Science.gov (United States)

    Mansouritorghabeh, H; Shirdel, A

    2016-02-01

    ESSENTIALS: Combined factor V (FV) and factor VIII (FVIII) deficiency (CF5F8D) is an autosomal recessive coagulation disorder. Desmopressin acetate (DDAVP) was intravenously infused in 20 adult patients with CF5F8D. DDAVP can enhance FVIII levels but has no effect on FV levels in patients with CF5F8D. DDAVP can be substituted for FVIII concentrates in patients with CF5F8D. Combined factor V (FV) and FVIII deficiency (CF5F8D) is a rare inherited autosomal recessive double-gene disorder most frequently seen in the Middle East. Although affected individuals have deficiency of two coagulation factors (range 5-30%), their bleeding tendencies are similar to patients who have deficiency of a single coagulation factor at the same level. The mainstay of their treatment is infusion of FVIII concentrate and fresh frozen plasma. Here, the effect of intravenous infusion of desmopressin acetate (DDAVP) on elevation of coagulation FV and FVIII was investigated through a clinical trial in May 2015. In a registered controlled trial, DDAVP (dosage 0.3 μg kg(-1) ) was intravenously infused into 20 adult patients with CF5F8D over 20 min. After an hour, blood samples were collected and plasma levels of FV and FVIII were measured. This study revealed that DDAVP can enhance FVIII levels but has no effect on FV plasma concentration in patients with CF5F8D. Based on these findings, FVIII concentrates may be substituted for DDAVP in patients with CF5F8D. © 2015 International Society on Thrombosis and Haemostasis.

  15. Acrodermatitis due to zinc deficiency after combined vertical gastroplasty with jejunoileal bypass: case report

    Directory of Open Access Journals (Sweden)

    Selma Freire de Carvalho Cunha

    Full Text Available CONTEXT: Nutritional complications may occur after bariatric surgery, due to restriction of food intake and impaired digestion or absorption of nutrients. CASE REPORT: After undergoing vertical gastroplasty and jejunoileal bypass, a female patient presented marked weight loss and protein deficiency. Seven months after the bariatric surgery, she presented dermatological features compatible with acrodermatitis enteropathica, as seen from the plasma zinc levels, which were below the reference values (34.4 mg%. The skin lesions improved significantly after 1,000 mg/day of zinc sulfate supplementation for one week. CONCLUSIONS: The patient's evolution shows that the multidisciplinary team involved in surgical treatment of obesity should take nutritional deficiencies into consideration in the differential diagnosis of skin diseases, in order to institute early treatment.

  16. Problem of Combined Selenium and Iodine Deficiency in the Development of Thyroid Pathology

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    V.I. Pankiv

    2014-09-01

    Full Text Available The article organizes data on the role of iodine and selenium deficiency in the functioning of the thyroid gland (TG, its importance in the development of thyropathies. Markers needed to determine the provision of the organism with iodine and selenium are given, as well as deficiency conditions associated with these trace elements, and their physiological daily doses are recommended. It was concluded that the use of selenium compounds (average dose 75 μg/day and iodine (average dose 150 μg/day with the purpose of prevention or treatment in physiological doses is safe, can reduce the severity or inhibit pathological processes in TG, including improving the course of autoimmune diseases.

  17. Administration of CoQ10 analogue ameliorates dysfunction of the mitochondrial respiratory chain in a mouse model of Angelman syndrome.

    Science.gov (United States)

    Llewellyn, Katrina J; Nalbandian, Angèle; Gomez, Arianna; Wei, Don; Walker, Naomi; Kimonis, Virginia E

    2015-04-01

    Genetic defects in the UBE3A gene, which encodes for the imprinted E6-AP ubiquitin E3 ligase (UBE3A), is responsible for the occurrence of Angelman syndrome (AS), a neurodegenerative disorder which arises in 1 out of every 12,000-20,000 births. Classical symptoms of AS include delayed development, impaired speech, and epileptic seizures with characteristic electroencephalography (EEG) readings. We have previously reported impaired mitochondrial structure and reduced complex III in the hippocampus and cerebellum in the Ube3a(m-/p+) mice. CoQ10 supplementation restores the electron flow to the mitochondrial respiratory chain (MRC) to ultimately increase mitochondrial antioxidant capacity. A number of recent studies with CoQ10 analogues seem promising in providing therapeutic benefit to patients with a variety of disorders. CoQ10 therapy has been reported to be safe and relatively well-tolerated at doses as high as 3000mg/day in patients with disorders of CoQ10 biosynthesis and MRC disorders. Herein, we report administration of idebenone, a potent CoQ10 analogue, to the Ube3a(m-/p+) mouse model corrects motor coordination and anxiety levels, and also improves the expression of complexes III and IV in hippocampus CA1 and CA2 neurons and cerebellum in these Ube3a(m-/p+) mice. However, treatment with idebenone illustrated no beneficial effects in the reduction of oxidative stress. To our knowledge, this is the first study to suggest an improvement in mitochondrial respiratory chain dysfunction via bioenergetics modulation with a CoQ10 analogue. These findings may further elucidate possible cellular and molecular mechanism(s) and ultimately a clinical therapeutic approach/benefit for patients with Angelman syndrome. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. High-salt diet combined with elevated angiotensin II accelerates atherosclerosis in apolipoprotein E-deficient mice

    DEFF Research Database (Denmark)

    Johansson, Maria E; Bernberg, Evelina; Andersson, Irene J

    2009-01-01

    OBJECTIVES: High-salt diet likely elevates blood pressure (BP), thus increasing the risk of cardiovascular events. We hypothesized that a high-salt diet plays a critical role in subjects whose renin-angiotensin systems cannot adjust to variable salt intake, rendering them more susceptible...... to atherosclerosis. METHODS: Apolipoprotein E-deficient (ApoE-/-) mice received standard or high-salt diet (8%) alone or in combination with fixed angiotensin II (Ang II) infusion (0.5 microg/kg per min). BP was measured using telemetry, and plaque burden was assessed in the thoracic aorta and innominate artery. We...

  19. Combined impairment of nutritional parameters and thyroid homeostasis in mildly iodine-deficient children.

    Science.gov (United States)

    Centanni, M; Maiani, G; Vermiglio, F; Canettieri, G; Sanna, A L; Moretti, F; Trimarchi, F; Andreoli, M

    1998-02-01

    The relation between thyroid homeostasis and the biochemical parameters of subclinical protein malnutrition has been analyzed in schoolchildren in a rural area in the south of Italy, known to be moderately iodine-deficient. The sera of 32 children (15 males and 17 females aged 6 to 11 years) have been analyzed. These children were divided into two groups, according to thyroid function: (1) 16 euthyroid children (mean thyrotropin [TSH] 2.38 +/- .35 mU/L; 6 with goiter) and (2) 16 subclinical hypothyroid children (mean TSH 7.32 +/- 1.68 mU/L; 6 with goiter). Retinol circulating complex (RCC) components were determined in serum by high-performance liquid chromatography (HPLC) and radial immunodiffusion and the essential and nonessential amino acid levels by ion exchange chromatography. Reduced retinol binding protein (RBP) and transthyretin (TTR) levels were recorded in the sera of 11 of 32 (34%) and in 5 of 32 (16%) patients, respectively. The linear regression analysis revealed that RBP and TSH levels were inversely correlated (r = -0.514; p malnutrition. These results provide evidence that even mild protein-energy malnutrition may have detrimental effects on thyroid homeostasis in iodine-deficient areas.

  20. Features of Immune and Metabolic Changes in patients with Combined Endocrine Pathology and Vitamin D3 Deficiency

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    Yu.I. Komisarenko

    2014-06-01

    Methods. The examined patients with DM type 1 and type 2 combined with autoimmune thyroiditis had reduced levels of D3 vitamin. They were divided into two groups of 28 and 30 patients respectively. All patients with autoimmune thyroiditis had hypothyroidism. The levels of Th1-cytokine profile (IFN-γ, TNF-α, IL-2, IL-6, IL-12, Th2-profile (IL-4, IL-5 and IL-10 and IL-17 were determined. The amount of vitamin D3 was assessed by the level of 25(OHD. Results. The patients with combined endocrine disorders — DM and autoimmune thyroiditis (with hypothyroidism secondary to vitamin D3 deficiency had a significant increase in the background concentration of Th1-cytokine profile (IFN-γ, TNF-α, IL-2, IL-6, IL-12 and a reduced cytokine concentrations of Th2-cytokine profile (IL-4, IL-5 as well as IL-10 and IL-17. Conclusions. The presence of two endocrine diseases and florid vitamin D3 deficiency leads to an imbalance in the immune status of patients, supports an autoimmune inflammatory process and contributes to the progression or advanced development of complications. Further research may confirm the need for the use of vitamin D3 for the prevention and treatment of multiple endocrinopathy to correct metabolic and immunological changes.

  1. A rare case of coinheritance of Hemoglobin H disease and sickle cell trait combined with severe iron deficiency

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    Michael Medinger

    2011-12-01

    Full Text Available We present a case of a 40-year-old female from Turkey, who was referred to our outpatient clinic for an undetermined thalassemia and sickle cell trait. At first consultation hemoglobin was decreased (71 g/L with microcytosis (MCV 55.1 fL, and hypochromia (MCHC 239 g/L. The patient had severe iron deficiency. Brilliant cresyl blue staining showed >50% of the erythrocytes with typical Hemoglobin H (HbH inclusions. High-performance liquid chromatography (HPLC revealed normal levels of HbA2 and Hemoglobin F (HbF, and additionally a hemoglobin S (19%. Molecular diagnostics revealed the mutations α2 IVS-I donor site -5nt and a -- MED II deletion in the alpha gene complex and confirmed the heterozygote mutation of the beta-gene at codon 6 (HBB:c.20A>T; HbS. In conclusion, we present an extremely rare combination of HbH disease and sickle cell trait. This combination may explain the mild form of the HbH disease, with moderate anemia, splenomegaly but iron deficiency, rather than iron overload, as usually observed in HbH disease.

  2. Combined deficiency of iron and (n-3) fatty acids in male rats disrupts brain monoamine metabolism and produces greater memory deficits than iron deficiency or (n-3) fatty acid deficiency alone.

    Science.gov (United States)

    Baumgartner, Jeannine; Smuts, Cornelius M; Malan, Linda; Arnold, Myrtha; Yee, Benjamin K; Bianco, Laura E; Boekschoten, Mark V; Müller, Michael; Langhans, Wolfgang; Hurrell, Richard F; Zimmermann, Michael B

    2012-08-01

    Deficiencies of iron (Fe) (ID) and (n-3) fatty acids (FA) [(n-3)FAD] may impair brain development and function through shared mechanisms. However, little is known about the potential interactions between these 2 common deficiencies. We studied the effects of ID and (n-3)FAD, alone and in combination, on brain monoamine pathways (by measuring monoamines and related gene expression) and spatial working and reference memory (by Morris water maze testing). Using a 2 × 2 design, male rats were fed an ID, (n-3)FAD, ID+(n-3)FAD, or control diet for 5 wk postweaning (postnatal d 21-56) after (n-3)FAD had been induced over 2 generations. The (n-3)FAD and ID diets decreased brain (n-3) FA by 70-76% and Fe by 20-32%, respectively. ID and (n-3)FAD significantly increased dopamine (DA) concentrations in the olfactory bulb (OB) and striatum, with an additive 1- to 2-fold increase in ID+(n-3)FAD rats compared with controls (P working memory performance and the impairment positively correlated with DA concentrations in FC (r = 0.39; P = 0.026). Reference memory was impaired in the ID+(n-3)FAD rats (P memory than ID or (n-3)FAD alone.

  3. The fluorescence intensity of the lipophilic probe N-phenyl-1-naphthylamine responds to the oxidation-reduction state of the respiratory chain in everted membrane vesicles of Escherichia coli.

    Science.gov (United States)

    Sedgwick, E G; Bragg, P D

    1987-06-22

    N-Phenyl-1-naphthylamine (NPN), a reagent which has been used previously to probe the fluidity or microviscosity of the membrane lipids of intact cells of Escherichia coli, was found to respond to metabolic changes in everted inner membrane vesicles from this organism. NPN was bound to the vesicles to produce a steady-state level of fluorescence intensity. Addition of substrate or ATP did not alter the fluorescence. However, following complete removal of oxygen from the medium by oxidation of substrate through the respiratory chain, there was an increase in the fluorescence of NPN. Reoxidation of the components of the respiratory chain by the addition of oxygen, ferricyanide, fumarate or nitrate decreased fluorescence to the steady-state level until the oxidant had been completely reduced. The fluorescence changes were insensitive to the state of energization of the membrane. It is proposed that NPN responds to the state of reduction of components of the respiratory chain either directly by reacting with a component of the chain or indirectly through an effect transmitted to the membrane by a change in the conformation of respiratory chain components.

  4. Hemoglobin Decrease with Iron Deficiency Induced by Daclatasvir plus Asunaprevir Combination Therapy for Chronic Hepatitis C Virus Genotype 1b.

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    Nobuyuki Matsumoto

    Full Text Available Decreased hemoglobin (Hb level has been supposed to be a relatively rare side effect of a combination therapy against hepatitis C virus that consists of the NS5A inhibitor daclatasvir (DCV and the NS3/4A protease inhibitor asunaprevir (ASV.The study was conducted in 75 patients with genotype 1b chronic hepatitis C virus infection who had started combination therapy with DCV and ASV at St. Marianna University School of Medicine Hospital between September 2014 and December 2014.Among the patients examined, decreased Hb level by ≥1.5 g/dL from the values at treatment initiation was observed in 11 individuals. This was accompanied by decreased mean corpuscular volume, and iron and ferritin levels.These findings suggest that the mechanism of the phenomenon is caused by iron deficiency. The underlying mechanism and clinical impacts will need to be further examined.

  5. Effects of radiation combined injury on hippocampal function are modulated in mice deficient in chemokine receptor 2 (CCR2).

    Science.gov (United States)

    Allen, Antiño R; Eilertson, Kirsten; Sharma, Sourabh; Schneider, Danielle; Baure, Jennifer; Allen, Barrett; Rosi, Susanna; Raber, Jacob; Fike, John R

    2013-07-01

    Chemokines and their receptors play a crucial role in normal brain function as well as in pathological conditions such as injury and disease-associated neuroinflammation. Chemokine receptor-2 (CCR2), which mediates the recruitment of infiltrating and resident microglia to sites of central nervous system (CNS) inflammation, is upregulated by ionizing irradiation and traumatic brain injury. Our objective was to determine if a deficiency in CCR2 and subsequent effects on brain microglia affect neurogenesis and cognitive function after radiation combined injury (RCI). CCR2 knock-out ⁻/⁻ and wild-type (WT) mice received 4 Gy of whole body ¹³⁷Cs irradiation. Immediately after irradiation, unilateral traumatic brain injury was induced using a controlled cortical impact system. Forty-four days postirradiation, animals were tested for hippocampus-dependent cognitive performance in the Morris water-maze. After cognitive testing, animals were euthanized and their brains snap frozen for immunohistochemical assessment of neuroinflammation (activated microglia) and neurogenesis in the hippocampal dentate gyrus. All animals were able to locate the visible and hidden platform locations in the water maze; however, treatment effects were seen when spatial memory retention was assessed in the probe trials (no platform). In WT animals that received combined injury, a significant impairment in spatial memory retention was observed in the probe trial after the first day of hidden platform training (first probe trial). This impairment was associated with increased neurogenesis in the ipsilateral hemisphere of the dentate gyrus. In contrast, CCR2⁻/⁻ mice, independent of insult showed significant memory retention in the first probe trial and there were no differences in the numbers of newly born neurons in the animals receiving irradiation, trauma or combined injury. Although the mechanisms involved are not clear, our data suggests that CCR2 deficiency can exert a protective

  6. Renal oncocytoma characterized by the defective complex I of the respiratory chain boosts the synthesis of the ROS scavenger glutathione.

    Science.gov (United States)

    Kürschner, Gerrit; Zhang, Qingzhou; Clima, Rosanna; Xiao, Yi; Busch, Jonas Felix; Kilic, Ergin; Jung, Klaus; Berndt, Nikolaus; Bulik, Sascha; Holzhütter, Hermann-Georg; Gasparre, Giuseppe; Attimonelli, Marcella; Babu, Mohan; Meierhofer, David

    2017-12-01

    Renal oncocytomas are rare benign tumors of the kidney and characterized by a deficient complex I (CI) enzyme activity of the oxidative phosphorylation (OXPHOS) system caused by mitochondrial DNA (mtDNA) mutations. Yet, little is known about the underlying molecular mechanisms and alterations of metabolic pathways in this tumor. We compared renal oncocytomas with adjacent matched normal kidney tissues on a global scale by multi-omics approaches, including whole exome sequencing (WES), proteomics, metabolomics, and metabolic pathway simulation. The abundance of proteins localized to mitochondria increased more than 2-fold, the only exception was a strong decrease in the abundance for CI subunits that revealed several pathogenic heteroplasmic mtDNA mutations by WES. We also observed renal oncocytomas to dysregulate main metabolic pathways, shunting away from gluconeogenesis and lipid metabolism. Nevertheless, the abundance of energy carrier molecules such as NAD + , NADH, NADP, ATP, and ADP were significantly higher in renal oncocytomas. Finally, a substantial 5000-fold increase of the reactive oxygen species scavenger glutathione can be regarded as a new hallmark of renal oncocytoma. Our findings demonstrate that renal oncocytomas undergo a metabolic switch to eliminate ATP consuming processes to ensure a sufficient energy supply for the tumor.

  7. [Correction of the combined vitamin deficiency in growing rats fed fiber enriched diets with different doses of vitamins].

    Science.gov (United States)

    Beketova, N A; Kodentsova, V M; Vrzhesinskaia, O A; Kosheleva, O V; Pereverzeva, O G; Sokol'nikov, A A; Aksenov, I V

    2014-01-01

    The effect of 5% dietary wheat bran (WB) on the correction of combined vitamin deficiency by two doses of vitamins (physiological and enhanced) has been analyzed using a rat model (8 groups, n = 8/group). Vitamin deficiency in male weanling Wistar rats (58.1 ± 0.5 g) was induced by 5-fold reduction of vitamin mixture amount in the feed and complete vitamin E, B1 and B2 exclusion from the mixture for 30 days, then deficit was corrected within 5 days. Rats from control group were fed a complete semisynthetic diet containing microcrystalline cellulose 2%. Vitamin deficient diet for 35 days resulted in reduced (p vitamin A in the liver by 25 fold, vitamin E and B1--2.0-2.3 fold, vitamin B2--by 40%, 25(OH)D blood plasma concentration--by 21% compared with the control. Feed consumption of the animals treated with vitamin deficient diet and WB was higher by 43% than in rats with vitamin deficit. Their rate of weight occupied the intermediate position between the rates of weight in deficit and in control animals, and they could not serve a full control to evaluate the WB impact on vitamin sufficiency. After filling the vitamin diet content to an adequate level vitamin E liver content was fully restored. To restore vitamins B1 and B2 liver level higher doses of vitamins (120-160% of adequate content) were required, and to restore the reduced levels of vitamin A in rat liver even 2-fold increased dose of vitamin A was insufficient. The diet enrichment with WB had no effect on vitamin B1 and B2 liver content, regardless of the amount of vitamins in the diet. Adding fiber to the diet of animals adequately provided with vitamins resulted in significantly 1,3-fold increase of 25(OH)D blood plasma concentration and a slight but significant decrease of α-tocopherol liver level by 16% as compared to rats not receiving WB. The enrichment of rat diet with dietary fibers worsened restoration of the reduced vitamin E status not only by filling vitamin content in the diet to an

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

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    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.

  9. Terminal deletion of 11q with significant late-onset combined immune deficiency.

    Science.gov (United States)

    Seppänen, Mikko; Koillinen, Hannele; Mustjoki, Satu; Tomi, Mölkänen; Sullivan, Kathleen E

    2014-01-01

    We report a 45-year old female adult patient with terminal deletion of chromosome 11q resulting in clinical phenotype of late-onset combined immunodeficiency. We describe the clinical phenotype and discuss the similarities between our patient and those with chromosome 22q11.2 deletion syndrome. Immunological evaluation included immunoglobulin levels, vaccine responses, number and function of T, NK and B cell subsets and comparative genomic hybridization test of blood and fibroblasts. The patient suffered from recurrent pneumococcal pneumonia and genital and cutaneous condylomas. She had a history of learning difficulties, dysmorphic features, autoimmune thyroiditis, chronic thrombocytopenia and severe asthma. We found Paris-Trousseau type thrombocytopenia, B-, T- and NK-lymphopenia, T cell oligoclonality and IgG hypogammaglobulinemia with inability to respond to pneumococcal polysaccharide, tetanus and diphtheria vaccines. A terminal deletion of chromosome 11q compatible with partial Jacobsen syndrome was found. This confirms Jacobsen syndrome as a chromosome deletion syndrome able to cause combined immunodeficiency.

  10. [Subacute combined degeneration of the spinal cord caused by vitamin B12 deficiency. Report of 11 cases].

    Science.gov (United States)

    Nogales-Gaete, Jorge; Jiménez, Paula; García, Pía; Sáez, David; Aracena, Rodrigo; González, Jorge; Lay-Son, Luis; Tenhamm, Eugenio; Figueroa, Tatiana; Chávez, Andrea; Oelker, Carolina; Vega, Luis

    2004-11-01

    Subacute combined degeneration is a clinical manifestation of vitamin B12 deficiency, that we observe with unusual frequency. To report a series of eleven patients with subacute combined degeneration. Retrospective analysis of 11 patients hospitalized in a public hospital in Santiago, between March 2001 and February 2003. All had a myelopathy of more than three weeks of evolution with serum vitamin B12 levels of less than 200 pg/ml. A risk factor was identified in 10 cases and the most common was an age over 60 years old. The main presenting symptom was the presence of paresthesias. On admission, sphincter dysfunction, posterior column and pyramidal syndromes coexisted in nine patients. A level of sensitive deficit was detected in six. Ten patients had macrocytosis and eight were anemic. Serum vitamin B12 was measured in ten and in nine, it was below 200 pg/ml. The mean lapse between onset of symptoms and treatment was eight months. All received intramuscular vitamin B12 in doses on 1,000 to 10,000 IU/day. Sphincter dysfunction and propioception were the first symptoms to improve. Subacute combined degeneration must be suspected in patients older than 60 years with a subacute myelopathic syndrome and low serum vitamin B12 levels.

  11. Binding of the Respiratory Chain Inhibitor Antimycin to theMitochondrial bc1 Complex: A New Crystal Structure Reveals an AlteredIntramolecular Hydrogen-Bonding Pattern

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Li-shar; Cobessi, David; Tung, Eric Y.; Berry, Edward A.

    2005-05-10

    Antimycin A (antimycin), one of the first known and most potent inhibitors of the mitochondrial respiratory chain, binds to the quinone reduction site of the cytochrome bc1 complex.Structure-activity-relationship studies have shown that the N-formylamino-salicyl-amide group is responsible for most of the binding specificity, and suggested that a low pKa for the phenolic OH group and an intramolecular H-bond between that OH and the carbonyl O of the salicylamide linkage are important. Two previous X-ray structures of antimycin bound to vertebrate bc1 complex gave conflicting results. A new structure reported here of the bovine mitochondrial bc1 complex at 2.28Angstrom resolution with antimycin bound, allows us for the first time to reliably describe the binding of antimycin and shows that the intramolecular hydrogen bond described in solution and in the small-molecule structure is replaced by one involving the NH rather than carbonyl O of the amide linkage, with rotation of the amide group relative to the aromatic ring. The phenolic OH and formylamino N form H-bonds with conserved Asp228 of cyt b, and the formylamino O H-bonds via a water molecule to Lys227. A strong density the right size and shape for a diatomic molecule is found between the other side of the dilactone ring and the alpha-A helix.

  12. Mitochondrial Respiratory Chain Inhibitors Involved in ROS Production Induced by Acute High Concentrations of Iodide and the Effects of SOD as a Protective Factor

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    Lingyan Wang

    2015-01-01

    Full Text Available A major source of reactive oxygen species (ROS generation is the mitochondria. By using flow cytometry of the mitochondrial fluorescent probe, MitoSOX Red, western blot of mitochondrial ROS scavenger Peroxiredoxin (Prx 3 and fluorescence immunostaining, ELISA of cleaved caspases 3 and 9, and TUNEL staining, we demonstrated that exposure to 100 μM KI for 2 hours significantly increased mitochondrial superoxide production and Prx 3 protein expression with increased expressions of cleaved caspases 3 and 9. Besides, we indicated that superoxide dismutase (SOD at 1000 unit/mL attenuated the increase in mitochondrial superoxide production, Prx 3 protein expression, and lactate dehydrogenase (LDH release and improved the relative cell viability at 100 μM KI exposure. However, SOD inhibitor diethyldithiocarbamic acid (DETC (2 mM, Rotenone (0.5 μM, a mitochondrial complex I inhibitor, and Antimycin A (10 μM, a complex III inhibitor, caused an increase in mitochondrial superoxide production, Prx 3 protein expression, and LDH release and decreased the relative cell viability. We conclude that the inhibitors of mitochondrial respiratory chain complex I or III may be involved in oxidative stress caused by elevated concentrations of iodide, and SOD demonstrates its protective effect on the Fischer rat thyroid cell line (FRTL cells.

  13. In male rats with concurrent iron and (n-3) fatty acid deficiency, provision of either iron or (n-3) fatty acids alone alters monoamine metabolism and exacerbates the cognitive deficits associated with combined deficiency

    NARCIS (Netherlands)

    Baumgartner, J.; Smuts, C.M.; Malan, L.; Arnold, M.; Yee, B.K.; Bianco, L.E.; Boekschoten, M.V.; Muller, M.R.; Langhans, W.; Hurrell, R.F.; Zimmermann, M.B.

    2012-01-01

    Concurrent deficiencies of iron (Fe) (ID) and (n-3) fatty acids [(n-3)FAD)] in rats can alter brain monoamine pathways and impair learning and memory. We examined whether repletion with Fe and DHA/EPA, alone and in combination, corrects the deficits in brain monoamine activity (by measuring

  14. Combined unicompartmental knee arthroplasty and anterior cruciate ligament reconstruction in knees with osteoarthritis and deficient anterior cruciate ligament.

    Science.gov (United States)

    Tian, Shaoqi; Wang, Bin; Wang, Yuanhe; Ha, Chengzhi; Liu, Lun; Sun, Kang

    2016-08-05

    Relative young and more active patients with osteoarthritis (OA) of the isolated medial femorotibial compartment in conjunction with anterior cruciate ligament (ACL) deficiency are difficult to treat. The aim of this study was to explore the early clinical outcomes of combined Oxford unicompartmental knee arthroplasty (UKA) and ACL reconstruction for the patients presenting ACL deficiency and isolated OA of the medial compartment. Twenty-eight patients were included into the study. All patients were treated by combined Oxford UKA and ACL reconstruction. Plain radiographs in the antero-posterior and lateral view and long-leg standing radiographs were routinely performed prior to and after surgery. Stress radiographs in valgus were additionally available in order to verify the well-preserved lateral compartment. The varus deformity of the knee prior to surgery and the valgus degree after surgery, the posterior slope of the tibial component and the range of motion (ROM) of the knee after surgery were measured and recorded. Clinical evaluations include Oxford Knee Score (OKS), Knee Society Score (KSS-clinical score; KSS-function score) and Tegner activity score. All the patients were followed up for 52 ± 8 months. The leg alignment showed 3.1 ± 0.6° of varus deformity prior to surgery and 4.0 ± 0.7° of valgus after surgery. The OKS, KSS and Tegner activity score improved significantly after surgery (P < 0.05). The mean ROM of the operated knee was 123.5 ± 2.8° at the last follow-up. The posterior slope of the tibial component was 3.9 ± 1.2°. A significant correlation was found between them according to the Pearson's correlation (r = 0.39, P = 0.03). There were 2 patients (7 %) with the complication of mobile bearing dislocation, and a second operation of replacing a thicker mobile bearing was performed for them. The early clinical data have shown that combined surgery of UKA and ACL reconstruction has revealed promising

  15. Conventional MRI for diagnosis of subacute combined degeneration (SCD) of the spinal cord due to vitamin B-12 deficiency.

    Science.gov (United States)

    Xiao, Cui-Ping; Ren, Cui-Ping; Cheng, Jing-Liang; Zhang, Yong; Li, Ying; Li, Bei-bei; Fan, Yi-Zhe

    2016-01-01

    Subacute combined degeneration of the spinal cord (SCD) is often found in vitamin B-12 deficiency and typically shows hyperintensity on T2-weighted images of the lateral and posterior columns. The purpose of the study was to evaluate the use of conventional magnetic resonance examination in diagnosing SCD. Thirty-six patients were clinically confirmed and retrospectively analyzed; conventional spine MRIs were available for all patients and eight of them had contrast enhancement MRIs. 19 out of 36 patients showed abnormal signal intensity on T2 weighted images with a sensitivity of 52.8%, among which 18 in the posterior aspect of the spinal cord and 1 in the anterior horn of the thoracic spinal cord The spinal cord abnormalities were seen at the cervical spine in 12 patients (33.3%) and at the thoracic spine in the other 7 patients (19.4%). Axial T2-weighted images showed symmetric linear T2-hyperintensity as an "inverted V" at the cervical spinal cord in 5 patients, which has been reported as a typical sign of SCD. For patients with thoracic spinal cord abnormalities, the bilateral paired nodular T2-hyperintensity looked like "binoculars" at the thoracic spinal cord. Only one out of the eight patients showed slight enhancement after injection with contrast agent. All the 36 patients reported clinical improvement after appropriate vitamin B-12 treatment. The two follow-up spine MRIs showed a decreased extent of the lesion. Therefore, conventional MRI is useful in the diagnosis and management of SCD caused by vitamin B-12 deficiency.

  16. In male rats with concurrent iron and (n-3) fatty acid deficiency, provision of either iron or (n-3) fatty acids alone alters monoamine metabolism and exacerbates the cognitive deficits associated with combined deficiency.

    Science.gov (United States)

    Baumgartner, Jeannine; Smuts, Cornelius M; Malan, Linda; Arnold, Myrtha; Yee, Benjamin K; Bianco, Laura E; Boekschoten, Mark V; Müller, Michael; Langhans, Wolfgang; Hurrell, Richard F; Zimmermann, Michael B

    2012-08-01

    Concurrent deficiencies of iron (Fe) (ID) and (n-3) fatty acids [(n-3)FAD)] in rats can alter brain monoamine pathways and impair learning and memory. We examined whether repletion with Fe and DHA/EPA, alone and in combination, corrects the deficits in brain monoamine activity (by measuring monoamines and related gene expression) and spatial working and reference memory [by Morris water maze (MWM) testing] associated with deficiency. Using a 2 × 2 design, male rats with concurrent ID and (n-3)FAD [ID+(n-3)FAD] were fed an Fe+DHA/EPA, Fe+(n-3)FAD, ID+DHA/EPA, or ID+(n-3)FAD diet for 5 wk [postnatal d 56-91]. Biochemical measures and MWM performance after repletion were compared to age-matched control rats. The provision of Fe in combination with DHA/EPA synergistically increased Fe concentrations in the olfactory bulb (OB) (Fe x DHA/EPA interaction). Similarly, provision of DHA/EPA in combination with Fe resulted in higher brain DHA concentrations than provision of DHA alone in the frontal cortex (FC) and OB (P FAD affects the DA and 5-HT pathways differently than combined repletion and exacerbates the cognitive deficits associated with combined deficiency.

  17. Combined deficiency of iron and (n-3) fatty acids in male rates disrupts brain monoamine metabolism and produces greater memory deficits than iron deficiency or (n-3) fatty acid deficiency alone

    NARCIS (Netherlands)

    Baumgartner, J.; Smuts, C.M.; Malan, L.; Arnold, M.; Yee, B.K.; Bianco, L.E.; Boekschoten, M.V.; Muller, M.R.; Langhans, W.; Hurrell, R.F.; Zimmermann, M.B.

    2012-01-01

    Deficiencies of iron (Fe) (ID) and (n-3) fatty acids (FA) [(n-3)FAD] may impair brain development and function through shared mechanisms. However, little is known about the potential interactions between these 2 common deficiencies. We studied the effects of ID and (n-3)FAD, alone and in

  18. Influence of sodium chloride on the regulation of Krebs cycle intermediates and enzymes of respiratory chain in mungbean (Vigna radiata L. Wilczek) seedlings.

    Science.gov (United States)

    Saha, Papiya; Kunda, Pranamita; Biswas, Asok K

    2012-11-01

    The effect of common salt (NaCl) on ion contents, Krebs cycle intermediates and its regulatory enzymes was investigated in growing mungbean (Vigna radiata L. Wilczek, B 105) seedlings. Sodium and chloride ion contents increased in both root and shoot whereas potassium ion content decreased in shoot of test seedlings with increasing concentrations of NaCl. Organic acids like pyruvate and citrate levels increased whereas malate level decreased under stress in both roots and shoots. Salt stress also variedly affected the activities of different enzymes of respiratory chain. The activity of pyruvate dehydrogenase (E.C. 1.2.4.1) decreased in 50 mM NaCl but increased in 100 mM and 150 mM concentrations, in both root and shoot samples. Succinate dehydrogenase (E.C. 1.3.5.1) activity was reduced in root whereas stimulated in shoot under increasing concentrations of salt. The activity of isocitrate dehydrogenase (E.C. 1.1.1.41) and malate dehydrogenase (E.C. 1.1.1.37) decreased in both root and shoot samples under salt stress. On the contrary, pretreatment of mungbean seeds with sublethal dose of NaCl was able to overcome the adverse effects of stress imposed by NaCl to variable extents with significant alterations of all the tested parameters, resulting in better growth and efficient respiration in mungbean seedlings. Thus, plants can acclimate to lethal level of salinity by pretreatment of seeds with sublethal level of NaCl, which serves to improve their health and production under saline condition, but the sublethal concentration of NaCl should be carefully chosen. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  19. Seeding efficiency of primitive human hematopoietic cells in nonobese diabetic/severe combined immune deficiency mice: implications for stem cell frequency assessment

    NARCIS (Netherlands)

    P.B. van Hennik; A.E. de Koning (Alexandra); R.E. Ploemacher (Robert)

    1999-01-01

    textabstractNonobese diabetic/severe combined immune deficiency (NOD/SCID) mouse repopulating cells (SRC) have been proposed to represent a more primitive human stem cell subset than the cobblestone area-forming cell (CAFC) week (wk) 6 or the long-term

  20. Combined pituitary hormone deficiency due to gross deletions in the POU1F1 (PIT-1) and PROP1 genes

    Science.gov (United States)

    Bertko, Eleonore; Klammt, Jürgen; Dusatkova, Petra; Bahceci, Mithat; Gonc, Nazli; ten Have, Louise; Kandemir, Nurgun; Mansmann, Georg; Obermannova, Barbora; Oostdijk, Wilma; Pfäffle, Heike; Rockstroh-Lippold, Denise; Schlicke, Marina; Tuzcu, Alpaslan Kemal; Pfäffle, Roland

    2017-01-01

    Pituitary development depends on a complex cascade of interacting transcription factors and signaling molecules. Lesions in this cascade lead to isolated or combined pituitary hormone deficiency (CPHD). The aim of this study was to identify copy number variants (CNVs) in genes known to cause CPHD and to determine their structure. We analyzed 70 CPHD patients from 64 families. Deletions were found in three Turkish families and one family from northern Iraq. In one family we identified a 4.96 kb deletion that comprises the first two exons of POU1F1. In three families a homozygous 15.9 kb deletion including complete PROP1 was discovered. Breakpoints map within highly homologous AluY sequences. Haplotype analysis revealed a shared haplotype of 350 kb among PROP1 deletion carriers. For the first time we were able to assign the boundaries of a previously reported PROP1 deletion. This gross deletion shows strong evidence to originate from a common ancestor in patients with Kurdish descent. No CNVs within LHX3, LHX4, HESX1, GH1 and GHRHR were found. Our data prove multiplex ligation-dependent probe amplification to be a valuable tool for the detection of CNVs as cause of pituitary insufficiencies and should be considered as an analytical method particularly in Kurdish patients. PMID:28356564

  1. Changes in rubisco, cysteine-rich proteins and antioxidant system of spinach (Spinacia oleracea L.) due to sulphur deficiency, cadmium stress and their combination.

    Science.gov (United States)

    Bagheri, Rita; Ahmad, Javed; Bashir, Humayra; Iqbal, Muhammad; Qureshi, M Irfan

    2017-03-01

    Sulphur (S) deficiency, cadmium (Cd) toxicity and their combinations are of wide occurrence throughout agricultural lands. We assessed the impact of short-term (2 days) and long-term (4 days) applications of cadmium (40 μg/g soil) on spinach plants grown on sulphur-sufficient (300 μM SO42-) and sulphur-deficient (30 μM SO42-) soils. Compared with the control (+S and -Cd), oxidative stress was increased by S deficiency (-S and -Cd), cadmium (+S and +Cd) and their combination stress (-S and +Cd) in the order of (S deficiency) leaf proteins showed a high vulnerability of rubisco large subunit (RbcL) to S deficiency. Rubisco small subunit (RbcS) was particularly sensitive to Cd as well as dual stress (+Cd and -S) but increased with Cd in the presence of S. Cysteine content in low molecular weight proteins/peptide was also affected, showing a significant increase under cadmium treatment. Components of ascorbate-glutathione antioxidant system altered their levels, showing the maximum decline in ascorbate (ASA), dehydroascorbate (DHA), total ascorbate (ASA + DHA, hereafter TA), glutathione (GSH) and total glutathione (GSH + GSSG, hereafter TG) under S deficiency. However, total ascorbate and total glutathione increased, besides a marginal increase in their reduced and oxidized forms, when Cd was applied in the presence of sufficient S. Sulphur supply also helped in increasing the activity of superoxide dismutase (SOD), ascorbate peroxidase (APX), glutathione reductase (GR) and catalase (CAT) under Cd stress. However, their activity suffered by S deficiency and by Cd stress during S deficiency. Each stress declined the contents of soluble protein and photosynthetic pigments; the highest decline in contents of protein and pigments occurred under S deficiency and dual stress respectively. The fresh and dry weights, although affected adversely by every stress, declined most under dual stress. It may be concluded that an optimal level of S is required during Cd stress

  2. Clinical variability in neurohepatic syndrome due to combined mitochondrial DNA depletion and Gaucher disease

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    Julie Harvengt

    2014-01-01

    Full Text Available A 1-year-old girl born to consanguineous parents presented with unexplained liver failure, leading to transplantation at 19 months. Subsequent partial splenectomy for persistent cytopenia showed the presence of foamy cells, and Gaucher disease was confirmed by homozygosity for the p.Leu483Pro mutation in the GBA gene. She was treated by enzyme replacement therapy (ERT. Clinical follow-up showed mild developmental delay, strabismus, nystagmus and oculomotor apraxia. Biochemical studies revealed multiple respiratory chain deficiencies and a mosaic pattern of deficient complex IV immunostaining in liver and fibroblast. Molecular analysis identified a mtDNA depletion syndrome due to the homozygous p.Pro98Leu mutation in MPV17. A younger sister unaffected by mtDNA depletion, presented with pancytopenia and hepatosplenomegaly. ERT for Gaucher disease resulted in visceral normalization without any neurological symptom. A third sister, affected by both conditions, had marked developmental delay, strabismus and ophthalmoplegia but no liver cirrhosis. In conclusion, intrafamilal variability occurs in MPV17-related disease. The combined pathological effect of Gaucher and mitochondrial diseases can negatively impact neurological and liver functions and influence the outcome in consanguineous families. The immunocytochemical staining of OXPHOS protein in tissues and cultured cells is a powerful tool revealing mosaic pattern of deficiency pointing to mtDNA-related mitochondrial disorders.

  3. Effectiveness of allogeneic CD3AK cells on transplanted human renal cell cancer in mice with severe combined immune deficiency.

    Science.gov (United States)

    Ge, Lei; Shan, Zhongjie; Han, Qianhe; Zhang, Nan; Zhao, Yang

    2016-01-01

    To assess the activity of allogeneic anti-CD3 antibody induced activated killer (CD3AK) cells on transplanted human renal cell cancer (RCC) in mice with severe combined immune deficiency (SCID), thus to provide theoretical and experimental support for clinical application of allogeneic CD3AK cells in the treatment of RCC. A culture system which can massively increase allogeneic CD3AK cells was constructed. CCK-8 method was used to detect lethal effect of allogeneic CD3AK cells on human OS-RC-2 renal cancer cell line. Then, tumor-bearing mice models were constructed. SCID mice were randomly divided into four groups: group A (caudal vein was injected with allogeneic CD3AK cells before tumor bearing), group B (the control group of group A: caudal vein was injected with PBS before tumor bearing), group C (caudal vein was injected with allogeneic CD3AK cells after tumor bearing) and group D (the control group of group C: caudal vein was injected with PBS after tumor bearing), and spleen parameters were calculated to observe any inhibitory effect of allogeneic CD3AK cells on the growth of renal cancer cells, as well as their effect on the immune system of mice. Compared with the control groups B and D, spleen parameters of groups A and C increased significantly (p0.05); compared with the control groups B and D, tumor weight of groups A and C decreased significantly and tumors grew slowly (pcancer in mice with SCID. Also CD3AK cells expressed certain preventive effect on the development of implanted cancer in SCID mice; allogeneic CD3AK cells possessed antitumor activity and could enhance the immunologic functions of SCID mice with human renal cell-bearing cancer.

  4. Boron deficiency and concentrations and composition of phenolic compounds in Olea europaea leaves: a combined growth chamber and field study.

    Science.gov (United States)

    Liakopoulos, Georgios; Karabourniotis, George

    2005-03-01

    Boron deficiency is the most frequent micronutrient disorder in olive (Olea spp.) orchards. We tested the hypothesis that plant boron status affects phenolic metabolism, which, in turn, influences several ecophysiological traits of olive (Olea europaea L.) trees, by studying the effects of boron deficiency on leaf phenolic compounds of olive in a growth chamber experiment (CE) and a field experiment (FE). In the CE, a semi-hydroponic system was used to control nutrient supply. Plants received complete nutrient solution containing either 23 (control) or 0 microM H3BO3 (boron-deficient treatment). In the FE, boron-deficient trees were chosen based on visible boron-deficiency symptoms and analysis of their leaf boron concentration. Boron deficiency caused significant accumulation of phenolic compounds in leaves of CE plants (1.7 to 5.8 times more, depending on leaf age), but not in leaves of FE plants. However, in both experiments, the concentration of an unidentified phenolic compound, with a UV-spectrum resembling that of caffeic acid, increased in response to boron deficiency (by a factor of 40 to 184 in the CE and by a factor of three in the FE). Regression analysis showed that the concentration of this compound was negatively correlated to leaf boron concentration, irrespective of growth conditions and treatment. We conclude that, under field conditions, boron deficiency may not be the only factor determining the concentration of total phenolics, but it may be responsible for the accumulation of a distinct phenolic metabolite in olive leaves.

  5. Providing male rats deficient in iron and n-3 fatty acids with iron and alpha-linolenic acid alone affects brain serotonin and cognition differently from combined provision.

    Science.gov (United States)

    Baumgartner, Jeannine; Smuts, Cornelius M; Zimmermann, Michael B

    2014-06-13

    We recently showed that a combined deficiency of iron (ID) and n-3 fatty acids (n-3 FAD) in rats disrupts brain monoamine metabolism and produces greater memory deficits than ID or n-3 FAD alone. Providing these double-deficient rats with either iron (Fe) or preformed docosahexaenoic acid (DHA)/eicosapentaenoic acid (EPA) alone affected brain monoamine pathways differently from combined repletion and even exacerbated cognitive deficits associated with double-deficiency. Iron is a co-factor of the enzymes responsible for the conversion of alpha-linolenic acid (ALA) to EPA and DHA, thus, the provision of ALA with Fe might be more effective in restoring brain EPA and DHA and improving cognition in double-deficient rats than ALA alone. In this study we examined whether providing double-deficient rats with ALA and Fe, alone or in combination, can correct deficits in monoamine metabolism and cognition associated with double-deficiency. Using a 2 × 2 design, male rats with concurrent ID and n-3 FAD were fed an Fe + ALA, Fe + n-3 FAD, ID + ALA, or ID + n-3 FAD diet for 5 weeks (postnatal day 56-91). Biochemical measures, and spatial working and reference memory (using the Morris water maze) were compared to age-matched controls. In the hippocampus, we found a significant Fe × ALA interaction on DHA: Compared to the group receiving ALA alone, DHA was significantly higher in the Fe + ALA group. In the brain, we found significant antagonistic Fe × ALA interactions on serotonin concentrations. Provision of ALA alone impaired working memory compared with age-matched controls, while in the reference memory task ALA provided with Fe significantly improved performance. These results indicate that providing either iron or ALA alone to double-deficient rats affects serotonin pathways and cognitive performance differently from combined provision. This may be partly explained by the enhancing effect of Fe on the conversion of ALA to EPA and DHA.

  6. Mutation R96W in cytochrome P450c17 gene causes combined 17{alpha}-hydroxylase/17-20-lyase deficiency in two french canadian patients

    Energy Technology Data Exchange (ETDEWEB)

    LaFlamme, N.; Leblanc, J.F.; Mailloux, J. [Laval Univ., Quebec (Canada)

    1996-01-01

    Congenital adrenal hyperplasia (CAH) is the most frequent cause of adrenal insufficiency and ambiguous genitalia in newborn children. In contrast to CAH caused by 21{alpha}-hydroxylase and 11{beta}-hydroxylase deficiencies, which impairs steroid formation in the adrenal exclusively, 17{alpha}-hydroxylase/17,20-lyase deficiency impairs steroid biosynthesis in the adrenals and gonads. The sequence of CYP17 gene was determined by direct sequencing of asymmetric PCR products in two French-Canadian 46,XY pseudohermaphrodite siblings suffering from combined 17{alpha}-hydroxylase/17,20-lyase deficiency. The two patients are homozygous for the novel missense mutation R96W caused by a C to T transition converting codon Arg{sup 96} (CGG) into a Trp (TGG) in exon 1. Both parents are heterozygous for this missense mutation. We assessed the effect of the R96W mutation on 17{alpha}-hydroxylase/17,20-lyase activity by analysis of mutant enzyme, generated by site-directed mutagenesis, expressed in COS-1 cells. The presence of R96W substitution almost completely abolished the activity of the mutant protein. The present findings provide a molecular explanation for the signs and symptoms of combined 17 {alpha}-hydroxylase/17,20-lyase deficiency in these two patients and provide useful information on the structure-activity relationships of the P450c17 enzyme. 31 refs., 4 figs., 1 tab.

  7. Targeting BRCA1-BER deficient breast cancer by ATM or DNA-PKcs blockade either alone or in combination with cisplatin for personalized therapy.

    Science.gov (United States)

    Albarakati, Nada; Abdel-Fatah, Tarek M A; Doherty, Rachel; Russell, Roslin; Agarwal, Devika; Moseley, Paul; Perry, Christina; Arora, Arvind; Alsubhi, Nouf; Seedhouse, Claire; Rakha, Emad A; Green, Andrew; Ball, Graham; Chan, Stephen; Caldas, Carlos; Ellis, Ian O; Madhusudan, Srinivasan

    2015-01-01

    BRCA1, a key factor in homologous recombination (HR) repair may also regulate base excision repair (BER). Targeting BRCA1-BER deficient cells by blockade of ATM and DNA-PKcs could be a promising strategy in breast cancer. We investigated BRCA1, XRCC1 and pol β protein expression in two cohorts (n = 1602 sporadic and n = 50 germ-line BRCA1 mutated) and mRNA expression in two cohorts (n = 1952 and n = 249). Artificial neural network analysis for BRCA1-DNA repair interacting genes was conducted in 249 tumours. Pre-clinically, BRCA1 proficient and deficient cells were DNA repair expression profiled and evaluated for synthetic lethality using ATM and DNA-PKcs inhibitors either alone or in combination with cisplatin. In human tumours, BRCA1 negativity was strongly associated with low XRCC1, and low pol β at mRNA and protein levels (p BER deficient cells were sensitive to ATM and DNA-PKcs inhibitor treatment either alone or in combination with cisplatin and synthetic lethality was evidenced by DNA double strand breaks accumulation, cell cycle arrest and apoptosis. We conclude that XRCC1 and pol β expression status in BRCA1 negative tumours may have prognostic significance. BRCA1-BER deficient cells could be targeted by ATM or DNA-PKcs inhibitors for personalized therapy. Copyright © 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  8. Specific combination of compound heterozygous mutations in 17β-hydroxysteroid dehydrogenase type 4 (HSD17B4 defines a new subtype of D-bifunctional protein deficiency

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    McMillan Hugh J

    2012-11-01

    Full Text Available Abstract Background D-bifunctional protein (DBP deficiency is typically apparent within the first month of life with most infants demonstrating hypotonia, psychomotor delay and seizures. Few children survive beyond two years of age. Among patients with prolonged survival all demonstrate severe gross motor delay, absent language development, and severe hearing and visual impairment. DBP contains three catalytically active domains; an N-terminal dehydrogenase, a central hydratase and a C-terminal sterol carrier protein-2-like domain. Three subtypes of the disease are identified based upon the domain affected; DBP type I results from a combined deficiency of dehydrogenase and hydratase activity; DBP type II from isolated hydratase deficiency and DBP type III from isolated dehydrogenase deficiency. Here we report two brothers (16½ and 14 years old with DBP deficiency characterized by normal early childhood followed by sensorineural hearing loss, progressive cerebellar and sensory ataxia and subclinical retinitis pigmentosa. Methods and results Biochemical analysis revealed normal levels of plasma VLCFA, phytanic acid and pristanic acid, and normal bile acids in urine; based on these results no diagnosis was made. Exome analysis was performed using the Agilent SureSelect 50Mb All Exon Kit and the Illumina HiSeq 2000 next-generation-sequencing (NGS platform. Compound heterozygous mutations were identified by exome sequencing and confirmed by Sanger sequencing within the dehydrogenase domain (c.101C>T; p.Ala34Val and hydratase domain (c.1547T>C; p.Ile516Thr of the 17β-hydroxysteroid dehydrogenase type 4 gene (HSD17B4. These mutations have been previously reported in patients with severe-forms of DBP deficiency, however each mutation was reported in combination with another mutation affecting the same domain. Subsequent studies in fibroblasts revealed normal VLCFA levels, normal C26:0 but reduced pristanic acid beta-oxidation activity. Both DBP

  9. Modulation effect of blu-ray irradiation combined with comprehensive therapy on serum indexes of neonatal erythrocyte glucose-6-phosphate dehydrogenase deficiency-induced hyperbilirubinemia

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    Xuan Yang

    2016-01-01

    Full Text Available Objective: To study the modulation effect of blu-ray irradiation combined with comprehensive therapy on serum indexes of neonatal erythrocyte glucose-6-phosphate dehydrogenase deficiency-induced hyperbilirubinemia. Methods: A total of 42 cases of neonates with erythrocyte glucose-6-phosphate dehydrogenase deficiency-induced hyperbilirubinemia were chosen for study and randomly divided into observation group (n=21 and control group (n=21. Observation group received blu-ray irradiation combined with comprehensive treatment and control group only received routine treatment. Then bilirubin levels, bilirubin encephalopathy condition, anemia condition and oxidative stress degree of two groups were compared. Results: 12 h, 24 h and 48 h after treatment, serum TBIL, DBIL, IBIL, Hb, GSH and CAT contents of both groups showed decreasing trend and MDA contents showed increasing trend; serum TBIL, DBIL, IBIL, Hb, GSH and CAT contents of observation group were lower than those of control group and MDA contents were higher than those of control group. 6 d, 7 d and 8 d after treatment, serum S100 β and NSE contents of both groups showed decreasing trend and serum S100 β and NSE contents of observation group were lower than those of control group. Conclusion: Blu-ray irradiation combined with comprehensive therapy helps to reduce bilirubin levels of neonatal erythrocyte glucose-6-phosphate dehydrogenase deficiency-induced hyperbilirubinemia and protect nerve function, but it will aggravate anemia condition and oxidative stress degree, and needs attention and intervention in clinical practice.

  10. Leukoencephalopathy due to Complex II Deficiency and Bi-Allelic SDHB Mutations

    DEFF Research Database (Denmark)

    Grønborg, Sabine; Darin, Niklas; Miranda, Maria J

    2017-01-01

    Isolated complex II deficiency is a rare cause of mitochondrial disease and bi-allelic mutations in SDHB have been identified in only a few patients with complex II deficiency and a progressive neurological phenotype with onset in infancy. On the other hand, heterozygous SDHB mutations are a well......-known cause of familial paraganglioma/pheochromocytoma and renal cell cancer. Here, we describe two additional patients with respiratory chain deficiency due to bi-allelic SDHB mutations. The patients' clinical, neuroradiological, and biochemical phenotype is discussed according to current knowledge...... on complex II and SDHB deficiency and is well in line with previously described cases, thus confirming the specific neuroradiological presentation of complex II deficiency that recently has emerged. The patients' genotype revealed one novel SDHB mutation, and one SDHB mutation, which previously has been...

  11. Primary coenzyme Q10 deficiency presenting as fatal neonatal multiorgan failure.

    Science.gov (United States)

    Desbats, Maria Andrea; Vetro, Annalisa; Limongelli, Ivan; Lunardi, Giada; Casarin, Alberto; Doimo, Mara; Spinazzi, Marco; Angelini, Corrado; Cenacchi, Giovanna; Burlina, Alberto; Rodriguez Hernandez, Maria Angeles; Chiandetti, Lino; Clementi, Maurizio; Trevisson, Eva; Navas, Placido; Zuffardi, Orsetta; Salviati, Leonardo

    2015-09-01

    Coenzyme Q10 deficiency is a clinically and genetically heterogeneous disorder, with manifestations that may range from fatal neonatal multisystem failure, to adult-onset encephalopathy. We report a patient who presented at birth with severe lactic acidosis, proteinuria, dicarboxylic aciduria, and hepatic insufficiency. She also had dilation of left ventricle on echocardiography. Her neurological condition rapidly worsened and despite aggressive care she died at 23 h of life. Muscle histology displayed lipid accumulation. Electron microscopy showed markedly swollen mitochondria with fragmented cristae. Respiratory-chain enzymatic assays showed a reduction of combined activities of complex I+III and II+III with normal activities of isolated complexes. The defect was confirmed in fibroblasts, where it could be rescued by supplementing the culture medium with 10 μM coenzyme Q10. Coenzyme Q10 levels were reduced (28% of controls) in these cells. We performed exome sequencing and focused the analysis on genes involved in coenzyme Q10 biosynthesis. The patient harbored a homozygous c.545T>G, p.(Met182Arg) alteration in COQ2, which was validated by functional complementation in yeast. In this case the biochemical and morphological features were essential to direct the genetic diagnosis. The parents had another pregnancy after the biochemical diagnosis was established, but before the identification of the genetic defect. Because of the potentially high recurrence risk, and given the importance of early CoQ10 supplementation, we decided to treat with CoQ10 the newborn child pending the results of the biochemical assays. Clinicians should consider a similar management in siblings of patients with CoQ10 deficiency without a genetic diagnosis.

  12. [Observation on therapeutic effect of electroacupuncture combined with Chinese herbs for treatment of prolapse of lumbar intervertebral disc of yang deficiency and cold coagulation type].

    Science.gov (United States)

    Liu, Lan; Liu, Lei-geng; Lü, Ming; Ran, Wei-jun

    2009-08-01

    To search for an effective therapy for prolapse of lumbar intervertebral disc of yang deficiency and cold coagulation type. One hundred and twenty-six cases were randomly divided into a combined electroacupuncture and Chinese herb group (n=49), an electroacupuncture group (n=42) and a Chinese herb group (n=35). The combined electroacupuncture and Chinese herb group was treated with electroacupuncture at Dachangshu (BL 25), Guanyuanshu (BL 26), Xiaochangshu (BL 27) and Yaoyangguan (GV 3) and oral administration of Chinese herbs for cold-removing and yang-invigorating. The electroacupuncture group was treated with the same electroacupuncture treatment alone and the Chinese herb group with the same self Chinese herbs alone. The therapeutic effects were observed after treatment for 20 days, and the recurrence rates were followed up at 180 days after the last treatment among the three groups. The cured-markedly effective rate was 79.6% in the combined electroacupuncture and Chinese herb group, 54.8% in the electroacupuncture group and 51.4% in the Chinese herb group, the combined electroacupuncture and Chinese herb group being significantly better than both the electroacupuncture group and the Chinese herb group (both P0.05). The recurrence rate after 180 days was 15.4% in the combined electroacupuncture and Chinese herb group, 83.3% in the electroacupuncture group and 80.0% in the Chinese herb group, with more obvious decrease in the combined electroacupuncture and Chinese herb group (both Pprolapse of lumbar intervertebral disc of yang deficiency and cold coagulation type.

  13. Biofeedback Therapy Combined with Traditional Chinese Medicine Prescription Improves the Symptoms, Surface Myoelectricity, and Anal Canal Pressure of the Patients with Spleen Deficiency Constipation

    Directory of Open Access Journals (Sweden)

    Yi-Bo Yao

    2013-01-01

    Full Text Available In order to observe the clinical therapeutic effects of Yiqi Kaimi Prescription and biofeedback therapy on treating constipation with deficiency of spleen qi, the 30 cases in the control group were given oral administration of Yiqi Kaimi Prescription, in combination with anus-lifting exercise; the 30 cases in the treatment group were given biofeedback therapy on the basis of the afore mentioned methods for the control group. The TCM symptom scores and anorectal pressures before and after treatment were observed and evaluated. There were significant differences in TCM symptom scores, anorectal pressure, and clinical recovery rate before and after treatment. In the treatment group, the total recovery rate was 86.66%, while in the control group it was 50%; there were significant differences between the two groups (P<0.01. Yiqi Kaimi Prescription coupled with biofeedback therapy is clinically effective for treating constipation with deficiency of spleen qi, and thus this method is applicable for functional constipation with deficiency of spleen qi.

  14. Biofeedback therapy combined with traditional chinese medicine prescription improves the symptoms, surface myoelectricity, and anal canal pressure of the patients with spleen deficiency constipation.

    Science.gov (United States)

    Yao, Yi-Bo; Cao, Yong-Qing; Guo, Xiu-Tian; Yi, Jin; Liang, Hong-Tao; Wang, Chen; Lu, Jin-Gen

    2013-01-01

    In order to observe the clinical therapeutic effects of Yiqi Kaimi Prescription and biofeedback therapy on treating constipation with deficiency of spleen qi, the 30 cases in the control group were given oral administration of Yiqi Kaimi Prescription, in combination with anus-lifting exercise; the 30 cases in the treatment group were given biofeedback therapy on the basis of the afore mentioned methods for the control group. The TCM symptom scores and anorectal pressures before and after treatment were observed and evaluated. There were significant differences in TCM symptom scores, anorectal pressure, and clinical recovery rate before and after treatment. In the treatment group, the total recovery rate was 86.66%, while in the control group it was 50%; there were significant differences between the two groups (P < 0.01). Yiqi Kaimi Prescription coupled with biofeedback therapy is clinically effective for treating constipation with deficiency of spleen qi, and thus this method is applicable for functional constipation with deficiency of spleen qi.

  15. The effect of a combined oral calcium and vitamin D supplement for treating mild to moderate vitamin D deficiency in postmenopausal women

    Directory of Open Access Journals (Sweden)

    Terry Golombick

    2008-03-01

    Full Text Available Terry Golombick, Terry DiamondDepartment of Endocrinology, St George Hospital, Kogarah, Sydney, NSW, AustraliaObjective: To evaluate the efficacy of a combined calcium and vitamin D (Ca-D3 supplement for vitamin D deficiency in a small group of postmenopausal women.Methods: A prospective open label 3 month-study.Participants: 23 postmenopausal women (mean age 61.2 yrs with vitamin D deficiency were given a combined oral Ca-D3 supplement called “Osteoblast”. The supplement comprises 500 mg elemental calcium and 500 IU of cholecalciferol. The dosing regimen comprised a loading dose of 1000 IU of cholecalciferol per day for one month (two tablets and thereafter a maintenance dose of 500 IU of cholecalciferol per day for 2 months (one tablet.Outcome measure: Serum was collected for calcium, 25 hydroxyvitamin D3 (25OHD3, and PTH measurements, as well as early morning 2-hour urine calcium/creatinine excretion index (Uca/creat. Specimens were collected at baseline and after 3 months of therapy. Data are reported as mean ± 1 standard error and 95% confi dence intervals.Results: Data was available for the 21 subjects who completed the study. Two subjects (9% withdrew because of gastrointestinal intolerance. There were 3 subjects with moderate (12.5–24 nmol/L and 18 with mild (25–49 nmol/L vitamin D deficiency. Ten subjects (48% had secondary hyperparathyroidism. Following the oral Ca-D3 combination, serum 25OHD3 levels normalised in all subjects with 18 (86% subjects achieving values of greater than 70 nmol/L. Serum 25OHD3 levels increased from 36 (31–41 to 91 (79–102 nmol/L (p = 0.0001, increasing by an average of 152% over the 3-month period. There was a corresponding 38% decrease in serum PTH concentrations at 3 months (5.1 + 0.6 pmol/L, compared with baseline (8.0 + 1 pmol/L (p = 0.001. No subject developed hypercalcemia, but an elevated Uca/creat excretion index occurred in one subjects.Conclusions: A combined oral Ca-D3 product

  16. Vitamin D for combination photodynamic therapy of skin cancer in individuals with vitamin D deficiency: Insights from a preclinical study in a mouse model of squamous cell carcinoma

    Science.gov (United States)

    Anand, Sanjay; Thomas, Erik; Hasan, Tayyaba; Maytin, Edward V.

    2016-03-01

    Combination photodynamic therapy (cPDT) in which vitamin D (VD) is given prior to aminolevulinate, a precursor (pro-drug) for protoporphyrin IX (PpIX), is an approach developed in our laboratory. We previously showed that 1α,25- dihydroxyvitamin D3 (calcitriol), given prior to PDT, enhances accumulation of PpIX and improves cell death post-PDT in a mouse skin cancer model. However, since calcitriol poses a risk for hypercalcemia, we replaced systemic calcitriol with oral cholecalciferol (D3), administered as a high (tenfold, "10K") diet over a ten-day period. Here, we ask whether VD deficiency might alter the response to cPDT. Nude mice were fed a VD-deficient diet for at least 4 weeks ("deficient"); controls were fed a normal 1,000 IU/kg diet ("1K"). Human A431 cells were implanted subcutaneously and mice were switched to the 10K diet or continued on their baseline diets (controls). In other experiments, mice received a human equivalent dose of 50,000 IU D3 by oral gavage, to simulate administration of a single, high-dose VD pill. At various times, tumors were harvested and serum was collected to measure levels of VD metabolic intermediates. A significant increase in PpIX levels and in the expression of differentiation and proliferation markers in tumor tissue was observed after VD supplementation of both the deficient and 1K mice. Further results describing mechanistic details of PpIX enhancement through alteration of heme- and VD-metabolic enzyme levels will be presented. Based on these results, a clinical study using oral vitamin D prior to PDT for human skin cancer should be performed.

  17. Exome sequencing identifies NFS1 deficiency in a novel Fe-S cluster disease, infantile mitochondrial complex II/III deficiency.

    Science.gov (United States)

    Farhan, Sali M K; Wang, Jian; Robinson, John F; Lahiry, Piya; Siu, Victoria M; Prasad, Chitra; Kronick, Jonathan B; Ramsay, David A; Rupar, C Anthony; Hegele, Robert A

    2014-01-01

    Iron-sulfur (Fe-S) clusters are a class of highly conserved and ubiquitous prosthetic groups with unique chemical properties that allow the proteins that contain them, Fe-S proteins, to assist in various key biochemical pathways. Mutations in Fe-S proteins often disrupt Fe-S cluster assembly leading to a spectrum of severe disorders such as Friedreich's ataxia or iron-sulfur cluster assembly enzyme (ISCU) myopathy. Herein, we describe infantile mitochondrial complex II/III deficiency, a novel autosomal recessive mitochondrial disease characterized by lactic acidemia, hypotonia, respiratory chain complex II and III deficiency, multisystem organ failure and abnormal mitochondria. Through autozygosity mapping, exome sequencing, in silico analyses, population studies and functional tests, we identified c.215G>A, p.Arg72Gln in NFS1 as the likely causative mutation. We describe the first disease in man likely caused by deficiency in NFS1, a cysteine desulfurase that is implicated in respiratory chain function and iron maintenance by initiating Fe-S cluster biosynthesis. Our results further demonstrate the importance of sufficient NFS1 expression in human physiology.

  18. Diminished exercise capacity and mitochondrial bc1 complex deficiency in tafazzin-knockdown mice.

    Directory of Open Access Journals (Sweden)

    Corey ePowers

    2013-04-01

    Full Text Available The phospholipid, cardiolipin, is essential for maintaining mitochondrial structure and optimal function. Cardiolipin-deficiency in humans, Barth syndrome, is characterized by exercise intolerance, dilated cardiomyopathy, neutropenia and 3-methyl-glutaconic aciduria. The causative gene is the mitochondrial acyl-transferase, tafazzin that is essential for remodeling acyl chains of cardiolipin. We sought to determine metabolic rates in tafazzin-deficient mice during resting and exercise, and investigate the impact of cardiolipin deficiency on mitochondrial respiratory chain activities. Tafazzin knockdown in mice markedly impaired oxygen consumption rates during an exercise, without any significant effect on resting metabolic rates. CL-deficiency resulted in significant reduction of mitochondrial respiratory reserve capacity in neonatal cardiomyocytes that is likely to be caused by diminished activity of complex-III, which requires CL for its assembly and optimal activity. Our results may provide mechanistic insights of Barth syndrome pathogenesis.

  19. Biochemical markers of vitamin B12 deficiency combined in one diagnostic parameter: the age-dependence and association with cognitive function and blood hemoglobin.

    Science.gov (United States)

    Fedosov, Sergey N

    2013-06-25

    Vitamin B12 deficiency is diagnosed by measurements of total B12, holo-transcobalamin (holoTC), methylmalonic acid (MMA) and total homocysteine (Hcy) in blood. Results of the individual biochemical tests are often contradictory. Here the four markers are combined to achieve a more reliable indication of the B12 status. The results are aligned with hemoglobin and cognitive score. Databases from the literature were plotted in coordinates x=(holoTC·B12)(1∕2), y=1∕2·log10(MMA·Hcy), where distribution of points revealed the subgroups characterized by logarithmic ratios lr=log10[(holoTC·B12)/(MMA·Hcy)]. Distance between the subgroups w=lr(Test)-lr(Normal) was taken as a robust biochemical indicator of B12 status ("wellness parameter"). The dependence of lr(Normal) vs. age was described by a mathematical function to correct parameter w. The B12 status was defined as "excellent" (w≈+0.4), "normal" (w≈0), "transitional" (w≈-0.5), "deficient" (w≈-1.7) and "pernicious" (w≈-3.0). The groups of individuals with either w≥0 or w≤-1 exhibited the statistically significant differences in both hemoglobin and cognitive score. Analogous assessment of B12 status by the individual markers agreed with only one out of two physiological characteristics. Combined parameter w is a reliable diagnostic tool. Copyright © 2013 Elsevier B.V. All rights reserved.

  20. Age modulates Fe3O4 nanoparticles liver toxicity: dose-dependent decrease in mitochondrial respiratory chain complexes activities and coupling in middle-aged as compared to young rats.

    Science.gov (United States)

    Baratli, Yosra; Charles, Anne-Laure; Wolff, Valérie; Ben Tahar, Lotfi; Smiri, Leila; Bouitbir, Jamal; Zoll, Joffrey; Sakly, Mohsen; Auger, Cyril; Vogel, Thomas; Abdelmelek, Hafedh; Tebourbi, Olfa; Geny, Bernard

    2014-01-01

    We examined the effects of iron oxide nanoparticles (IONPs) on mitochondrial respiratory chain complexes activities and mitochondrial coupling in young (3 months) and middle-aged (18 months) rat liver, organ largely involved in body iron detoxification. Isolated liver mitochondria were extracted using differential centrifugations. Maximal oxidative capacities (V(max), complexes I, III, and IV activities), V(succ) (complexes II, III, and IV activities), and V tmpd, (complex IV activity), together with mitochondrial coupling (V(max)/V0) were determined in controls conditions and after exposure to 250, 300, and 350 μ g/ml Fe3O4 in young and middle-aged rats. In young liver mitochondria, exposure to IONPs did not alter mitochondrial function. In contrast, IONPs dose-dependently impaired all complexes of the mitochondrial respiratory chain in middle-aged rat liver: V(max) (from 30 ± 1.6 to 17.9 ± 1.5; P V(succ) (from 33.9 ± 1.7 to 24.3 ± 1.0; P V(tmpd) (from 43.0 ± 1.6 to 26.3 ± 2.2 µmol O2/min/g protein; P < 0.001) using Fe3O4 350 µg/ml. Mitochondrial coupling also decreased. Interestingly, 350 μ g/ml Fe3O4 in the form of Fe(3+) solution did not impair liver mitochondrial function in middle-aged rats. Thus, IONPs showed a specific toxicity in middle-aged rats suggesting caution when using it in old age.

  1. Age Modulates Fe3O4 Nanoparticles Liver Toxicity: Dose-Dependent Decrease in Mitochondrial Respiratory Chain Complexes Activities and Coupling in Middle-Aged as Compared to Young Rats

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    Yosra Baratli

    2014-01-01

    Full Text Available We examined the effects of iron oxide nanoparticles (IONPs on mitochondrial respiratory chain complexes activities and mitochondrial coupling in young (3 months and middle-aged (18 months rat liver, organ largely involved in body iron detoxification. Isolated liver mitochondria were extracted using differential centrifugations. Maximal oxidative capacities (Vmax, complexes I, III, and IV activities, Vsucc (complexes II, III, and IV activities, and Vtmpd, (complex IV activity, together with mitochondrial coupling (Vmax/V0 were determined in controls conditions and after exposure to 250, 300, and 350 μg/ml Fe3O4 in young and middle-aged rats. In young liver mitochondria, exposure to IONPs did not alter mitochondrial function. In contrast, IONPs dose-dependently impaired all complexes of the mitochondrial respiratory chain in middle-aged rat liver: Vmax (from 30 ± 1.6 to 17.9 ± 1.5; P<0.001, Vsucc (from 33.9 ± 1.7 to 24.3 ± 1.0; P<0.01, Vtmpd (from 43.0 ± 1.6 to 26.3 ± 2.2 µmol O2/min/g protein; P<0.001 using Fe3O4 350 µg/ml. Mitochondrial coupling also decreased. Interestingly, 350 μg/ml Fe3O4 in the form of Fe3+ solution did not impair liver mitochondrial function in middle-aged rats. Thus, IONPs showed a specific toxicity in middle-aged rats suggesting caution when using it in old age.

  2. Inhibitory effect of the combination therapy of simvastatin and pinocembrin on atherosclerosis in apoE-deficient mice

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    Sang Hui

    2012-12-01

    Full Text Available Abstract The present study was performed to investigate the effects of the combination therapy of pinocembrin and simvastatin on the atherosclerotic lesions development in the ApoE−/− mice. Methods Eight-week-old male ApoE−/− mice were fed high fat diet (HFD and treated with simvastatin (10 mg/kg per day, pinocembrin (20 mg/kg per day, or the combination therapy (simvastatin 5 mg/kg per day and pinocembrin 20 mg/kg per day for 14 weeks. The serum lipid levels, nitric oxide (NO, endothelin (ET, superoxide dismutase (SOD and malondialdehyde (MDA were determined with spectrophotometric measurement and ELISA assay. Vascular endothelial growth factor (VEGF in serum and aortic root was detected. En face analyses of atherosclerotic lesion in whole aorta and aortic root sections were performed with plaque staining using oil red O. Results The combination treatment with simvastatin and pinocembrin resulted in significantly decreased levels of serum total cholesterol, triglycerides and low-density lipoprotein cholesterol, augmented NO levels and SOD activity, inhibited ET and VEGF expression. Immunohistochemistry of aortic valve sections revealed that the combination therapy also suppressed the expression of VEGF induced by HFD. In addition, HFD-induced arterial wall lipid disposition displayed by oil red O staining was reduced significantly in aortic root and whole aorta en face in the combination administrated mice. The effect of the combination was superior to simvastatin alone. Conclusion The combination of simvastatin and pinocembrin synergistically inhibited atherosclerotic lesion development in ApoE−/− mice with hyperlipidemia, which is partially dependent on the protective of vascular endothelium.

  3. Phosphorus deficiency affects the allocation of below-ground resources to combined cluster roots and nodules in Lupinus albus.

    Science.gov (United States)

    Thuynsma, Rochelle; Valentine, Alex; Kleinert, Aleysia

    2014-02-15

    Lupins can rely on both cluster roots and nodules for P acquisition and biological nitrogen fixation (BNF), respectively. The resource allocation (C, N and P) between cluster roots and nodules has been largely understudied during P-deficient conditions. The aim of this investigation was therefore to determine the changes in resource allocation between these organs during fluctuations in P supply. Lupinus albus was cultivated in sand culture for 3 weeks, with either sufficient (2 mM high) or limiting (0.1 mM low) P supply. Although variation on P supply had no effect on the total biomass, there were significant differences in specialised below-ground organ allocation to cluster roots and nodule formation. Cluster root formation and the associated C-costs increased during low P supply, but at sufficient P-supply the construction and growth respiration costs of cluster roots declined along with their growth. In contrast to the cluster root decline at high P supply, there was an increase in nodule growth allocation and corresponding C-costs. However, this was not associated with an increase in BNF. Since cluster roots were able to increase P acquisition under low P conditions, this below-ground investment may also have benefited the P nutrition of nodules. These findings provide evidence that when lupins acquire N via BNF in their nodules, there may be a trade-off in resource allocation between cluster roots and nodules. Copyright © 2013 Elsevier GmbH. All rights reserved.

  4. Combined effect of the environmental factors as ionizing radiation and a chronic iodine deficiency on the thyroid gland and the immune condition

    Energy Technology Data Exchange (ETDEWEB)

    Danyarova, L. [Department of Endocrynology, Research Institute of Cardiology and Internal Medicine, Almaty (Kazakhstan)

    2012-07-01

    The Semipalatinsk Test Site was the primary testing venue for the Soviet Union's nuclear weapons. It is located on the steppe in northeast Kazakhstan. The tragic situation of the Semipalatinsk region is an acute and chronic radiation, repeated in big and small doses and a total absence of territorial decontamination, created unique conditions for study of the long term influence of the radiation doses on the health of the population. The Semipalatinsk region of the Republic of Kazakhstan belongs also to an area of moderate and pronounced iodine deficiency. The purpose of the research is to study the prevalence of a thyroid gland pathology and the condition of a cytokine immune link that is likely to be influenced by a combine effect of ionizing radiation and a chronic iodine deficiency. 1100 people passed through the investigation and it appears that 56, 75% of them had a thyroid pathology. Thyroid gland functional condition analysis (TSH, FT3, FT4 a-TG, a-TPO) has shown the prevalence of a subclinical hypothyroidism (33%). 28, 8% resulted in the presence of antibodies to thyroglobulin and the thyroid peroxides, whereas in the areas located further to the nuclear range, the percentage was only 13, 0%

  5. Screen for abnormal mitochondrial phenotypes in mouse embryonic stem cells identifies a model for succinyl-CoA ligase deficiency and mtDNA depletion

    Directory of Open Access Journals (Sweden)

    Taraka R. Donti

    2014-02-01

    Full Text Available Mutations in subunits of succinyl-CoA synthetase/ligase (SCS, a component of the citric acid cycle, are associated with mitochondrial encephalomyopathy, elevation of methylmalonic acid (MMA, and mitochondrial DNA (mtDNA depletion. A FACS-based retroviral-mediated gene trap mutagenesis screen in mouse embryonic stem (ES cells for abnormal mitochondrial phenotypes identified a gene trap allele of Sucla2 (Sucla2SAβgeo, which was used to generate transgenic mice. Sucla2 encodes the ADP-specific β-subunit isoform of SCS. Sucla2SAβgeo homozygotes exhibited recessive lethality, with most mutants dying late in gestation (e18.5. Mutant placenta and embryonic (e17.5 brain, heart and muscle showed varying degrees of mtDNA depletion (20–60%. However, there was no mtDNA depletion in mutant liver, where the gene is not normally expressed. Elevated levels of MMA were observed in embryonic brain. SCS-deficient mouse embryonic fibroblasts (MEFs demonstrated a 50% reduction in mtDNA content compared with wild-type MEFs. The mtDNA depletion resulted in reduced steady state levels of mtDNA encoded proteins and multiple respiratory chain deficiencies. mtDNA content could be restored by reintroduction of Sucla2. This mouse model of SCS deficiency and mtDNA depletion promises to provide insights into the pathogenesis of mitochondrial diseases with mtDNA depletion and into the biology of mtDNA maintenance. In addition, this report demonstrates the power of a genetic screen that combines gene trap mutagenesis and FACS analysis in mouse ES cells to identify mitochondrial phenotypes and to develop animal models of mitochondrial dysfunction.

  6. High-salt diet combined with elevated angiotensin II accelerates atherosclerosis in apolipoprotein E-deficient mice

    DEFF Research Database (Denmark)

    Johansson, Maria E; Bernberg, Evelina; Andersson, Irene J

    2009-01-01

    OBJECTIVES: High-salt diet likely elevates blood pressure (BP), thus increasing the risk of cardiovascular events. We hypothesized that a high-salt diet plays a critical role in subjects whose renin-angiotensin systems cannot adjust to variable salt intake, rendering them more susceptible to athe......-salt diet combined with fixed high Ang II levels accelerates atherogenesis synergistically, beyond the effect of BP....

  7. Sideroblastic anaemia and primary adrenal insufficiency due to a mitochondrial respiratory chain disorder in the absence of mtDNA deletion.

    Science.gov (United States)

    O'Grady, Michael J; Monavari, Ahmad A; Cotter, Melanie; Murphy, Nuala P

    2015-02-26

    A fatigued 8-year-old boy was found to have sideroblastic anaemia (haemoglobin 7.8 g/dL) which over time became transfusion dependent. Subtle neurological dysfunction, initially manifesting as mild spastic diplegia, was slowly progressive and ultimately led to wheelchair dependence. Elevated plasma lactate and urinary 3-methylglutaconate led to a muscle biopsy which confirmed partial complex IV deficiency. PCR in leucocytes and muscle was negative for mitochondrial DNA (mtDNA) deletions. Faltering growth prompted an insulin tolerance test which confirmed growth hormone sufficiency and adrenal insufficiency. Plasma renin was elevated and adrenal androgens were low, suggesting primary adrenal insufficiency. Glucocorticoid and mineralocorticoid replacement therapy was initiated. A renal tubular Fanconi syndrome and diabetes mellitus developed subsequently. Sideroblastic anaemia and primary adrenal insufficiency, both individually and collectively, are associated with mtDNA deletion; however, absence of the same does not exclude the possibility that sideroblastic anaemia and primary adrenal insufficiency are of mitochondrial origin. 2015 BMJ Publishing Group Ltd.

  8. [Succinate dehydrogenase (SDH)-deficient renal cell carcinoma].

    Science.gov (United States)

    Agaimy, A

    2016-03-01

    Succinate dehydrogenase (SDH) represents a type II mitochondrial complex related to the respiratory chain and Krebs cycle. The complex is composed of four major subunits, SDHA, SDHB, SDHC and SDHD. The oncogenic role of this enzyme complex has only recently been recognized and the complex is currently considered an important oncogenic signaling pathway with tumor suppressor properties. In addition to the familial paraganglioma syndromes (types 1-5) as prototypical SDH-related diseases, many other tumors have been defined as SDH-deficient, in particular a subset of gastrointestinal stromal tumors (GIST), rare hypophyseal adenomas, a subset of pancreatic neuroendocrine neoplasms (recently added) and a variety of other tumor entities, the latter mainly described as rare case reports. As a central core subunit responsible for the integrity of the SDH complex, the expression of SDHB is lost in all SDH-deficient neoplasms irrespective of the specific SDH subunit affected by a genetic mutation in addition to concurrent loss of the subunit specifically affected by genetic alteration. Accordingly, all SDH-deficient neoplasms are by definition SDHB-deficient. The SDH-deficient renal cell carcinoma (RCC) has only recently been well-characterized and it is included as a specific subtype of RCC in the new World Health Organization (WHO) classification published in 2016. In this review, the major clinicopathological, immunohistochemical and genetic features of this rare disease entity are presented and discussed in the context of the broad differential diagnosis.

  9. [A Case of Subacute Combined Degeneration Caused by Vitamin B12 Deficiency in a Cervical Spondylosis Surgery Referral].

    Science.gov (United States)

    Yokoyama, Kunio; Kawanishi, Masahiro; Sugie, Akira; Yamada, Makoto; Tanaka, Hidekazu; Ito, Yutaka; Kuroiwa, Toshihiko

    2016-12-01

    A 62-year-old man with a 1-year history of numbness of the extremities, clumsiness, and gait disorder was diagnosed with cervical spondylotic myelopathy at a neighboring clinic and referred to our institution for surgery. The patient had undergone a total gastrectomy 6 years previously. Flattening of the cervical cord, associated with diffuse cervical spondylosis and intramedullary intensity change, was observed on magnetic resonance imaging of the cervical spine. Neurological examination revealed decreased vibratory and position sense in all limbs, with posterior funiculus-based neurological symptoms. Blood biochemistry revealed decreased vitamin B12(VB12)levels and megaloblastic anemia. On the basis of these findings, the patient was diagnosed with subacute combined degeneration(SCD). The patient was treated with VB12 for 3 months; the gait disorder resolved and the intramedullary intensity changes in the posterior column of the medulla oblongata, thoracicus, and spinal cord were no longer observed. SCD is a pathological condition in which recovery of neurological function may be achieved through early administration of VB12. In some cases, it is difficult to differentiate between this condition and cervical spondylotic myelopathy because both diseases exhibit progressive spinal symptoms. The medical history and results of neurological evaluations of the patient are important for an accurate diagnosis, and should therefore not be overlooked.

  10. Combination Therapy with c-Met and Src Inhibitors Induces Caspase-Dependent Apoptosis of Merlin-Deficient Schwann Cells and Suppresses Growth of Schwannoma Cells.

    Science.gov (United States)

    Fuse, Marisa A; Plati, Stephani Klingeman; Burns, Sarah S; Dinh, Christine T; Bracho, Olena; Yan, Denise; Mittal, Rahul; Shen, Rulong; Soulakova, Julia N; Copik, Alicja J; Liu, Xue Zhong; Telischi, Fred F; Chang, Long-Sheng; Franco, Maria Clara; Fernandez-Valle, Cristina

    2017-11-01

    Neurofibromatosis type 2 (NF2) is a nervous system tumor disorder caused by inactivation of the merlin tumor suppressor encoded by the NF2 gene. Bilateral vestibular schwannomas are a diagnostic hallmark of NF2. Mainstream treatment options for NF2-associated tumors have been limited to surgery and radiotherapy; however, off-label uses of targeted molecular therapies are becoming increasingly common. Here, we investigated drugs targeting two kinases activated in NF2-associated schwannomas, c-Met and Src. We demonstrated that merlin-deficient mouse Schwann cells (MD-MSC) treated with the c-Met inhibitor, cabozantinib, or the Src kinase inhibitors, dasatinib and saracatinib, underwent a G 1 cell-cycle arrest. However, when MD-MSCs were treated with a combination of cabozantinib and saracatinib, they exhibited caspase-dependent apoptosis. The combination therapy also significantly reduced growth of MD-MSCs in an orthotopic allograft mouse model by greater than 80% of vehicle. Moreover, human vestibular schwannoma cells with NF2 mutations had a 40% decrease in cell viability when treated with cabozantinib and saracatinib together compared with the vehicle control. This study demonstrates that simultaneous inhibition of c-Met and Src signaling in MD-MSCs triggers apoptosis and reveals vulnerable pathways that could be exploited to develop NF2 therapies. Mol Cancer Ther; 16(11); 2387-98. ©2017 AACR . ©2017 American Association for Cancer Research.

  11. The impact of Folate Pathway Polymorphisms Combined to Nutritional Deficiency As a Maternal Predisposition Factor for Down Syndrome

    Directory of Open Access Journals (Sweden)

    C. B. Santos-Rebouças

    2008-01-01

    Full Text Available Polymorphisms in genes encoding folate metabolizing enzymes have been linked to an increased risk of maternal chromosomal nondisjunction in several populations. With the purpose of evaluating this relationship, we compared the frequencies of 677C>T and 1298A>C polymorphisms in the methylenetetrahydrofolate reductase gene (MTHFR and 66A>G in the methionine synthase reductase gene (MTRR between 103 young mothers of Down syndrome (DS individuals and 108 control mothers, whose offspring was karyotypically normal, correlating it with an estimative of folate and – related micronutrients levels intake. Maternal and paternal transmission frequencies of MTHFR 677T allele were also examined to access potential parent-of-origin effects. PCR-RFLP for genomic DNA was accomplished and allele/genotype frequencies differences were determined using the x2 test, whereas pattern of transmission of the MTHFR 677 allele was analyzed by transmission disequilibrium test. None of the polymorphisms seemed to be more frequent in case mothers than in controls, either individually or combined. The estimative of nutritional intake revealed that folate consumption median was inadequate in both groups, whereas methionine and zinc consumption medians were significantly greater in control mothers. It suggests that such interaction between genetic profile and environment could predispose this sub group of women to have a DS child. Additional studies focusing the interaction between nutritional intakes, biochemical data and folate pathway polymorphisms are needed to confirm the present results. The possibility of neutralize the biochemical negative effects of folate-related polymorphisms through oral supplementation could provide new targets for DS prevention.

  12. A Patient with Complex I Deficiency Caused by a Novel ACAD9 Mutation Not Responding to Riboflavin Treatment

    DEFF Research Database (Denmark)

    Nouws, Jessica; Wibrand, Flemming; van den Brand, Mariël

    2014-01-01

    Here we report a patient with a new pathogenic mutation in ACAD9. Shortly after birth she presented with respiratory insufficiency and a high lactate level. At age 7 weeks, she was diagnosed with severe hypertrophic cardiomyopathy and she suffered from muscle weakness and hypotonia. Her condition...... deteriorated during intercurrent illnesses and she died at 6 months of age in cardiogenic shock. Analysis of respiratory chain activities in muscle and fibroblasts revealed an isolated complex I deficiency. A genome-wide screen for homozygosity revealed several homozygous regions. Four candidate genes were...

  13. [Ergometric and pathologic study of a family with complex I deficiency].

    Science.gov (United States)

    Tojo, M; Ogawa, N; Takeuchi, M; Toyama, J; Torigoe, K; Sato, S; Takahashi, R; Koga, Y; Nonaka, I

    1992-01-01

    We studied a family with a myopathic form of complex I deficiency with regard to the clinical symptoms, usefulness of the exercise tolerance test with an ergometer for screening of mitochondrial abnormalities, pathological findings in biopsied muscles and genetics. In this family, none of the members had disorders of the central nervous system, such as convulsions, mental deterioration or stroke-like episodes. In the two affected generations, three mothers and three children had mitochondrial abnormalities. Two children were diagnosed as having complex I deficiency. One of them, an 8-year-old girl with normal psychomotor development during infancy, began to experience easy fatigability at about 3 years of age. At the age of 5 years, she experienced respiratory distress and became unconscious. Thereafter, she had similar episodic respiratory problems with lactic acidosis. Ragged-red fibers and respiratory chain enzyme defects were detected in the biopsied muscle. Another child, a 15-year-old boy with easy fatigability but no muscle weakness, had normal respiratory chain enzyme activities and a normal oxysogram: oxygen consumption showed a normal responses when malate and pyruvate were added as substrates for the isolated mitochondria. His muscle pathology revealed rare ragged-red fibers and abnormal subsarcolemmal mitochondrial aggregation. An investigation with an ergometer showed elevated serum lactate and pyruvate levels. Only one mother had muscle weakness and hyper-lactic acidemia. The other two mothers had no muscle symptoms, but abnormal results were obtained with the ergometer.(ABSTRACT TRUNCATED AT 250 WORDS)

  14. [Medicinal vesiculation combined with quick cupping at Shenque (CV 8) for allergic rhinitis with syndrome of yang deficiency: a randomized controlled trial].

    Science.gov (United States)

    Ke, Zheng-hua; Long, Sheng-hua

    2014-09-01

    To compare the clinical efficacy differences between medicinal vesiculation combined with quick cupping at Shenque (CV 8) and regular medication for allergic rhinitis with syndrome of yang deficiency. Eighty-two cases were randomly divided into an observation group (42 cases) and a control group (40 cases). The observation group was treated with medicinal vesiculation combined with quick cupping at Shenque (CV 8). The medicinal vesiculation was applied at Feishu (BL 13), Gaohuang (BL 43), Fengmen (BL 12), Mingmen (GV 4) on the dog days in the summer, one treatment on the 1st dog-day, 2nd dog-day and last dog-day respectively with an interval of 10 days between two treatments. Three treatments were taken as one course, and totally one course was given. The quick cupping was applied at Shenque (CV 8), once a day, ten treatments were taken as one course, and totally three courses was given. The control group was treated with oral administration of loratadine and nasal spray of budesonide. The loratadine was given 10 mg per time, once a day for continuous 14 days; budesonide was given once a day, ten treatments were taken as one course, and totally three courses was given. The clinical efficacy in two groups after treatment was observed, and the contents of immune globulin E (IgE), interleukin-4 (IL-4), interleukin-5 (IL-5) and tumor necrosis factor-α (TNF-α) in peripheral serum were measured before and after the treatments. Of all the 82 patients, 79 cases completed the treatment, and 1 patient in the observation group and 2 patients in the control group dropped out. The effective rate was 87.8% (36/41) in the observation group, which was superior to 78.9% (30/38) in the control group (Ptreatment, both groups effectively reduced the contents of IgE, IL-4, IL-5 and TNF-α, and the observation group had superior effect on reducing IgE and IL-4 to the control group (Pcupping at Shenque (CV 8) have better effect for allergic rhinitis with syndrome of yang deficiency

  15. Combined Increases in Mitochondrial Cooperation and Oxygen Photoreduction Compensate for Deficiency in Cyclic Electron Flow in Chlamydomonas reinhardtii[W][OPEN

    Science.gov (United States)

    Dang, Kieu-Van; Plet, Julie; Tolleter, Dimitri; Jokel, Martina; Cuiné, Stéphan; Carrier, Patrick; Auroy, Pascaline; Richaud, Pierre; Johnson, Xenie; Alric, Jean; Allahverdiyeva, Yagut; Peltier, Gilles

    2014-01-01

    During oxygenic photosynthesis, metabolic reactions of CO2 fixation require more ATP than is supplied by the linear electron flow operating from photosystem II to photosystem I (PSI). Different mechanisms, such as cyclic electron flow (CEF) around PSI, have been proposed to participate in reequilibrating the ATP/NADPH balance. To determine the contribution of CEF to microalgal biomass productivity, here, we studied photosynthesis and growth performances of a knockout Chlamydomonas reinhardtii mutant (pgrl1) deficient in PROTON GRADIENT REGULATION LIKE1 (PGRL1)–mediated CEF. Steady state biomass productivity of the pgrl1 mutant, measured in photobioreactors operated as turbidostats, was similar to its wild-type progenitor under a wide range of illumination and CO2 concentrations. Several changes were observed in pgrl1, including higher sensitivity of photosynthesis to mitochondrial inhibitors, increased light-dependent O2 uptake, and increased amounts of flavodiiron (FLV) proteins. We conclude that a combination of mitochondrial cooperation and oxygen photoreduction downstream of PSI (Mehler reactions) supplies extra ATP for photosynthesis in the pgrl1 mutant, resulting in normal biomass productivity under steady state conditions. The lower biomass productivity observed in the pgrl1 mutant in fluctuating light is attributed to an inability of compensation mechanisms to respond to a rapid increase in ATP demand. PMID:24989042

  16. Disease: H01349 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available mutations can cause Leigh-like disease with combined deficiency of multiple mitochondrial respiratory chain enzymes and pyruvate dehydrogenase. Orphanet J Rare Dis 8:188 (2013) ...

  17. Effects of NM-3 on lymphatic vessel density and vascular endothelial growth factor of colon cancer in orthotopic implantation model of a severe combined immune deficiency mice

    Directory of Open Access Journals (Sweden)

    Jin-Shui Zhu

    2010-12-01

    Full Text Available The molecular mechanisms involved colon cancer tumorigenesis and development of colon cancer remain unclear. The aim of this study is to explore the inhibitive effects of NM-3 on lymphatic vessel density and vascular endothelial growth factor of micrometastatic lesion of orthotopic implantated colon cancer in the severe combined immune deficiency (SCID nude mice. Human colon cancer SW1116 cells were orthotopically implantated into the colon of the nude mice. Twenty-eight SCID nude mice were randomly divided into four groups (7 mice for each group after one week feeding and then the nude mice were treated with carboplatin and NM-3 via intraperitoneal injection twice a week for 8 weeks. The mice were sacrificed after 8 weeks and the vascular endothelial growth factor-C (VEGF-C, VEGF-D, VEGF-R-3 and lymphatic vessel density (LVD were analyzed using immunohistochemistry staining assay. LVD in NM-3 treated mice was significantly lower than that of control (normal saline treated mice. The expression of VEGF-C, VEGF-D, and VEGF-R-3 and the expression of mRNA of VEGF-C, VEGF-D, and VEGF-R-3 in NM-3 treated mice were significantly lower than that of control mice. The NM-3 inhibited the growth of colon cancer in the SCID mice of orthotopic implantatation model, and this effect may be related to the inhibitive effects of NM-3 on the lymphangiogenesis and vascular endothelial growth factor in colon cancer. NM-3 and carboplatin played a synergistic role in inhibiting lymphangiogenesis of human colon cancer in SCID nude mice and the further investigation of molecular mechanisms involved in colon cancer metastasis will provide an important evidence for understanding of lymphangiogenesis of human colon cancer.

  18. Combination tibial plateau leveling osteotomy and cranial closing wedge osteotomy of the tibia for the treatment of cranial cruciate ligament-deficient stifles with excessive tibial plateau angle.

    Science.gov (United States)

    Talaat, Miriam B; Kowaleski, Michael P; Boudrieau, Randy J

    2006-12-01

    To describe a surgical technique, and outcome, for treatment of cranial cruciate ligament (CrCL) deficient stifle joints with excessive tibial plateau angle (TPA) by combined tibial plateau leveling osteotomy and cranial closing wedge osteotomy (TPLO/CCWO). Retrospective clinical study. Fifteen client-owned dogs (18 stifle joints). Medical records of dogs that had TPLO/CCWO were reviewed. Pre- and postoperative TPA, CCWO technique, method of fixation and complications were recorded. In-hospital re-evaluation of limb function and length of time to radiographic healing was reviewed. Long-term outcome was assessed by owner telephone interview. Mean pre- and postoperative TPA was 42 degrees and 8 degrees, respectively. The Slocum biradial saw was used to create the CCWO in 4 stifle joints (mean postoperative TPA, 16 degrees) and a sagittal saw was used in 14 stifle joints (mean postoperative TPA, 5 degrees). Postoperative surgical complications were documented in 77.8% of cases; including patellar tendon thickening (61.1%), and implant loosening or breakage (27.8%), seroma formation (11.1%), and local irritation (11.1%). A second surgical procedure was performed in one-third of cases primarily to retrieve implants. Mean time to documented radiographic healing was 18 weeks. Final in-hospital re-evaluation of limb function (mean, 23 weeks postoperatively) was recorded as no lameness in 73.3% and mild lameness in 26.7%. All interviewed owners were satisfied with outcome and 90.9% reported marked improvement or a return to preinjury status. Long-term clinical outcome of TPLO/CCWO was very good in dogs with excessive TPA, with high owner satisfaction. Longer healing times and a higher complication rate were observed compared with TPLO alone. TPLO/CCWO of the tibia in stifle joints with excessive TPA allows for full correction of the TPA to 5 degrees without eliminating buttress support of the tibial tuberosity.

  19. Lifetime exercise intolerance with lactic acidosis as key manifestation of novel compound heterozygous ACAD9 mutations causing complex I deficiency.

    Science.gov (United States)

    Schrank, Bertold; Schoser, Benedikt; Klopstock, Thomas; Schneiderat, Peter; Horvath, Rita; Abicht, Angela; Holinski-Feder, Elke; Augustis, Sarunas

    2017-05-01

    We report a 36-year-old female having lifetime exercise intolerance and lactic acidosis with nausea associated with novel compound heterozygous Acyl-CoA dehydrogenase 9 gene (ACAD9) mutations (p.Ala390Thr and p.Arg518Cys). ACAD9 is an assembly factor for the mitochondrial respiratory chain complex I. ACAD9 mutations are recognized as frequent causes of complex I deficiency. Our patient presented with exercise intolerance, rapid fatigue, and nausea since early childhood. Mild physical workload provoked the occurrence of nausea and vomiting repeatedly. Her neurological examination, laboratory findings and muscle biopsy demonstrated no abnormalities. A bicycle spiroergometry provoked significant lactic acidosis during and following exercise pointing towards a mitochondrial disorder. Subsequently, the analysis of respiratory chain enzyme activities in muscle revealed severe isolated complex I deficiency. Candidate gene sequencing revealed two novel heterozygous ACAD9 mutations. This patient report expands the mutational and phenotypic spectrum of diseases associated with mutations in ACAD9. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. 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.

  1. Combined IL-12 receptor and IgA deficiency in an adult man intestinally infested by an unknown, non-cultivable mycobacterium

    DEFF Research Database (Denmark)

    Schejbel, L; Rasmussen, E M; Kemp, Helle Bruunsgaard

    2011-01-01

    Interleukin-12 receptor deficiency is a well-described cause of human susceptibility to infection with low-virulent mycobacteria and Salmonella species. We identified a male patient presenting in his late forties with severe gastroenteropathy because of outbred infestation by a previously unknown...

  2. Comparison of response to 2-years’ growth hormone treatment in children with isolated growth hormone deficiency, born small for gestational age, idiopathic short stature, or multiple pituitary hormone deficiency: combined results from two large observational studies

    Directory of Open Access Journals (Sweden)

    Lee Peter A

    2012-07-01

    Full Text Available Abstract Background Few studies have compared the response to growth hormone (GH treatment between indications such as isolated growth hormone deficiency (IGHD, born small for gestational age (SGA, idiopathic short stature (ISS, and multiple pituitary hormone deficiency (MPHD. The aim of this analysis of data, collected from two large ongoing observational outcome studies, was to evaluate growth and insulin-like growth factor-I (IGF-I response data for children of short stature with IGHD, MPHD, SGA, or ISS following two years of treatment with the recombinant GH product Norditropin® (Novo Nordisk A/S, Bagsværd, Denmark. Methods Analysis of auxologic data from two ongoing prospective observational studies, NordiNet® International Outcomes Study (NordiNet® IOS and NovoNet®/American Norditropin® Studies: Web-enabled Research (ANSWER Program®. Results 4,582 children aged p = 0.047; p  0.001 vs. IGHD, respectively. Height gain was comparable between IGHD and MPHD. In pre-pubertal children vs. total population, height SDS change after two years was: IGHD, +1.24 vs. +0.97; SGA, +1.17 vs. +1.03; ISS, +1.04 vs. +0.84; and MPHD, +1.16 vs. +0.99 (all p  Conclusions After two years’ GH treatment, change in height SDS was greater in SGA and less in ISS, compared with IGHD; the discrepancy in responses may be due to the disease nature or confounders (i.e. age. Height SDS increase was greatest in pre-pubertal children, supporting early treatment initiation to optimize growth outcomes.

  3. A case of anemia caused by combined vitamin B12 and iron deficiency manifesting as short stature and delayed puberty Anemia

    Directory of Open Access Journals (Sweden)

    Seung Min Song

    2010-05-01

    Full Text Available Anemia caused by vitamin B12 deficiency resulting from inadequate dietary intake is rare in children in the modern era because of improvements in nutritional status. However, such anemia can be caused by decreased ingestion or impaired absorption and/ or utilization of vitamin B12. We report the case of an 18-year-old man with short stature, prepubertal sexual maturation, exertional dyspnea, and severe anemia with a hemoglobin level of 3.3 g/dL. He had a history of small bowel resection from 50 cm below the Treitz ligament to 5 cm above the ileocecal valve necessitated by midgut volvulus in the neonatal period. Laboratory tests showed deficiencies of both vitamin B12 and iron. A bone marrow examination revealed dyserythropoiesis and low levels of hemosiderin particles, and a cytogenetic study disclosed a normal karyotype. After treatment with parenteral vitamin B12 and elemental iron, both anemia and growth showed gradual improvement. This is a rare case that presented with short stature and delayed puberty caused by nutritional deficiency anemia in Korea.

  4. Cell-permeable succinate prodrugs bypass mitochondrial complex I deficiency

    Science.gov (United States)

    Ehinger, Johannes K.; Piel, Sarah; Ford, Rhonan; Karlsson, Michael; Sjövall, Fredrik; Frostner, Eleonor Åsander; Morota, Saori; Taylor, Robert W.; Turnbull, Doug M.; Cornell, Clive; Moss, Steven J.; Metzsch, Carsten; Hansson, Magnus J.; Fliri, Hans; Elmér, Eskil

    2016-01-01

    Mitochondrial complex I (CI) deficiency is the most prevalent defect in the respiratory chain in paediatric mitochondrial disease. This heterogeneous group of diseases includes serious or fatal neurological presentations such as Leigh syndrome and there are very limited evidence-based treatment options available. Here we describe that cell membrane-permeable prodrugs of the complex II substrate succinate increase ATP-linked mitochondrial respiration in CI-deficient human blood cells, fibroblasts and heart fibres. Lactate accumulation in platelets due to rotenone-induced CI inhibition is reversed and rotenone-induced increase in lactate:pyruvate ratio in white blood cells is alleviated. Metabolomic analyses demonstrate delivery and metabolism of [13C]succinate. In Leigh syndrome patient fibroblasts, with a recessive NDUFS2 mutation, respiration and spare respiratory capacity are increased by prodrug administration. We conclude that prodrug-delivered succinate bypasses CI and supports electron transport, membrane potential and ATP production. This strategy offers a potential future therapy for metabolic decompensation due to mitochondrial CI dysfunction. PMID:27502960

  5. 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.

  6. IGF-1 deficiency in combination with a low basic hBD-2 and hBD-3 gene expression might counteract malignant transformation in pleomorphic adenomas in vitro.

    Science.gov (United States)

    Winter, J; Mohr, S; Pantelis, A; Kraus, D; Allam, J P; Novak, N; Reich, R; Martini, M; Jepsen, S; Götz, W; Wenghoefer, M

    2012-02-01

    This study investigated the IGF-1-influence on oncological relevant genes in pleomorphic adenomas. Therefore A64-tumor cells were stimulated by recombinant IGF-1. After RNA-extraction, transcript levels of hBD-1, hBD-2, hBD-3, DEFA1/3, DEFA4, S100A4, Psoriasin, DOC-1, EGF, EGFR, and IGFR were analyzed by qRT-PCR at t = 0, 4, 8, 24, 48, and 72 hr. The gene-products were visualized by immunostaining. A64-tumor-cells were deficient for hBD-1 and IGF-1. IGF-1 downregulates hBD-2 and hBD-3 without influencing hBD-1-expression. IGF-1 only slightly affects DEFA1/3-, DEFA4-, S100A4-, Psoriasin-, DOC-1-, EGF-, EGFR-, and IGFR-gene-expression. IGF-1-deficiency combined with low basic hBD-2-gene-expression and hBD-3-gene-expression might counteract, whereas hBD-1-deficiency promotes malignant transformation in pleomorphic adenomas.

  7. Novel Combined Immune Deficiency and Radiation Sensitivity Blended Phenotype in an Adult with Biallelic Variations in ZAP70 and RNF168

    Directory of Open Access Journals (Sweden)

    Ivan K. Chinn

    2017-05-01

    Full Text Available With the advent of high-throughput genomic sequencing techniques, novel genetic etiologies are being uncovered for previously unexplained Mendelian phenotypes, and the underlying genetic architecture of disease is being unraveled. Although most of these “mendelizing” disease traits represent phenotypes caused by single-gene defects, a percentage of patients have blended phenotypes caused by pathogenic variants in multiple genes. We describe an adult patient with susceptibility to bacterial, herpesviral, and fungal infections. Immunologic defects included CD8+ T cell lymphopenia, decreased T cell proliferative responses to mitogens, hypogammaglobulinemia, and radiation sensitivity. Whole-exome sequencing revealed compound heterozygous variants in ZAP70. Biallelic mutations in ZAP70 are known to produce a spectrum of immune deficiency that includes the T cell abnormalities observed in this patient. Analyses for variants in genes associated with radiation sensitivity identified the presence of a homozygous RNF168 variant of unknown significance. RNF168 deficiency causes radiosensitivity, immunodeficiency, dysmorphic features, and learning difficulties syndrome and may account for the radiation sensitivity. Thus, the patient was found to have a novel blended phenotype associated with multilocus genomic variation: i.e., separate and distinct genetic defects. These findings further illustrate the clinical utility of applying genomic testing in patients with primary immunodeficiency diseases.

  8. Growth hormone replacement delays the progression of chronic heart failure combined with growth hormone deficiency: an extension of a randomized controlled single-blind study.

    Science.gov (United States)

    Cittadini, Antonio; Marra, Alberto M; Arcopinto, Michele; Bobbio, Emanuele; Salzano, Andrea; Sirico, Domenico; Napoli, Raffaele; Colao, Annamaria; Longobardi, Salvatore; Baliga, Ragavendra R; Bossone, Eduardo; Saccà, Luigi

    2013-08-01

    This study sought to evaluate the efficacy and safety of long-term growth hormone (GH) replacement therapy in GH-deficient patients with chronic heart failure (CHF). Recent evidence indicates that growth hormone deficiency (GHD) affects as many as 40% of patients with CHF, and short-term GH replacement causes functional benefit. Whether long-term GH replacement also affects CHF progression is unknown. The study is an extension of a previous randomized, controlled single-blind trial that screened 158 consecutive CHF patients (New York Heart Association classes II to IV) and identified 63 who had GHD by the growth hormone releasing hormone plus arginine test. Fifty-six patients were randomized to receive either GH therapy or standard CHF therapy. Patients were evaluated at baseline and after a 4-year follow-up. The primary endpoint was peak oxygen consumption (VO2). Secondary endpoints included left ventricular (LV) ejection fraction and volumes, serum amino terminal fragment of the pro-hormone brain-type natriuretic peptide, quality of life, and safety. Seventeen patients in the GH group and 14 in the control group completed the study. In the GH group, peak VO2 improved over the 4-year follow-up. The treatment effect was 7.1 ± 0.7 ml/kg/min versus -1.8 ± 0.5 ml/kg/min in the GH and control groups, respectively. At 4 years, LV ejection fraction increased by 10 ± 3% in the GH group, whereas it decreased by 2 ± 5% in control patients. The treatment effect on LV end-systolic volume index was -22 ± 6 ml and 8 ± 3 ml/m(2) in the GH and control groups, respectively (all p < 0.001). No major adverse events were reported in the patients who received GH. Although this is a preliminary study, the finding suggests a new therapeutic approach to a large proportion of GHD patients with CHF. Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  9. Respostas de combinações de variedades copa e porta-enxerto de citros à deficiência hídrica Responses of citrus scion and rootstocks varieties combinations to water deficiency

    Directory of Open Access Journals (Sweden)

    Sérgio Luiz Rodrigues Donato

    2007-10-01

    Full Text Available O objetivo deste trabalho foi avaliar a influência de diferentes combinações de variedades copa e porta-enxertos sobre respostas de plantas de citros ao deficit hídrico em casa de vegetação. O delineamento utilizado foi o de blocos ao acaso, com cinco repetições no esquema fatorial: cinco variedades copa; dois porta-enxertos; e dois regimes hídricos. A tangerineira 'Poncan' é a variedade copa mais sensível ao deficit hídrico, expressado pelo potencial hídrico foliar, quando enxertada sobre o citrumeleiro 'Swingle'. Sob deficit hídrico severo, as variedades copa enxertadas sobre limoeiro 'Cravo' apresentam maior desenvolvimento da copa das plantas cítricas, em comparação ao citrumeleiro 'Swingle'.The aim of this work was to study the influence of different scion and rootstock combinations on responses of citrus plants to water deficit in greenhouse. The experimental design was formed by randomized blocks with five replications in the fallowing factorial scheme: five scion varieties; two rootstocks; and two hydro regimes. 'Poncã' tangerine is the scion variety more sensible to water deficit, expressed by leaf water potential, when grafted on 'Swingle' citrumelo. Under severe water deficit, the scion varieties grafted on 'Rangpur' lime present greater development of citric plants scion compared to 'Swingle' citrumelo.

  10. Iron deficiency

    DEFF Research Database (Denmark)

    Schou, Morten; Bosselmann, Helle; Gaborit, Freja

    2015-01-01

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

  11. Iron and a mixture of DHA and EPA supplementation, alone and in combination, affect bioactive lipid signalling and morbidity of iron deficient South African school children in a two-by-two randomised controlled trial.

    Science.gov (United States)

    Malan, L; Baumgartner, J; Zandberg, L; Calder, P C; Smuts, C M

    2016-02-01

    We recently reported that iron supplementation increased respiratory morbidity in iron deficient South African children. This increase, however, was attenuated when iron was provided in combination with a mixture of DHA/EPA. To explore potential underlying mechanisms, we examined the effects of iron and DHA/EPA, alone and in combination, on plasma lipid-derived immune modulator concentrations and related gene expression in peripheral blood mononuclear cells (PBMC). DHA/EPA decreased inflammatory 12-hydroxyeicosatetraenoic acid and tended to increase anti-inflammatory and pro-resolving 17-hydroxydocosahexaenoic acid (17-HDHA), while iron decreased 17-HDHA. However, in combination with iron, the anti-inflammatory effect of DHA/EPA was maintained. These biochemical changes may explain the prevention of iron-induced respiratory morbidity that we observed when iron was supplemented in combination with DHA/EPA during the 8.5 month randomised controlled trial and might lead to a safer approach of delivering iron supplementation. The study was registered at clinicaltrials.gov as NCT01092377. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. Neuronopathic Gaucher disease in the mouse: viable combined selective saposin C deficiency and mutant glucocerebrosidase (V394L) mice with glucosylsphingosine and glucosylceramide accumulation and progressive neurological deficits.

    Science.gov (United States)

    Sun, Ying; Liou, Benjamin; Ran, Huimin; Skelton, Matthew R; Williams, Michael T; Vorhees, Charles V; Kitatani, Kazuyuki; Hannun, Yusuf A; Witte, David P; Xu, You-Hai; Grabowski, Gregory A

    2010-03-15

    Gaucher disease is caused by defective acid beta-glucosidase (GCase) function. Saposin C is a lysosomal protein needed for optimal GCase activity. To test the in vivo effects of saposin C on GCase, saposin C deficient mice (C-/-) were backcrossed to point mutated GCase (V394L/V394L) mice. The resultant mice (4L;C*) began to exhibit CNS abnormalities approximately 30 days: first as hindlimb paresis, then progressive tremor and ataxia. Death occurred approximately 48 days due to neurological deficits. Axonal degeneration was evident in brain stem, spinal cord and white matter of cerebellum accompanied by increasing infiltration of the brain stem, cortex and thalamus by CD68 positive microglial cells and activation of astrocytes. Electron microscopy showed inclusion bodies in neuronal processes and degenerating cells. Accumulation of p62 and Lamp2 were prominent in the brain suggesting the impairment of autophagosome/lysosome function. This phenotype was different from either V394L/V394L or C-/- alone. Relative to V394L/V394L mice, 4L;C* mice had diminished GCase protein and activity. Marked increases (20- to 30-fold) of glucosylsphingosine (GS) and moderate elevation (1.5- to 3-fold) of glucosylceramide (GC) were in 4L;C* brains. Visceral tissues had increases of GS and GC, but no storage cells were found. Neuronal cells in thick hippocampal slices from 4L;C* mice had significantly attenuated long-term potentiation, presumably resulting from substrate accumulation. The 4L;C* mouse mimics the CNS phenotype and biochemistry of some type 3 (neuronopathic) variants of Gaucher disease and is a unique model suitable for testing pharmacological chaperone and substrate reduction therapies, and investigating the mechanisms of neuronopathic Gaucher disease.

  13. Treatment of CoQ(10 deficient fibroblasts with ubiquinone, CoQ analogs, and vitamin C: time- and compound-dependent effects.

    Directory of Open Access Journals (Sweden)

    Luis C López

    2010-07-01

    Full Text Available Coenzyme Q(10 (CoQ(10 and its analogs are used therapeutically by virtue of their functions as electron carriers, antioxidant compounds, or both. However, published studies suggest that different ubiquinone analogs may produce divergent effects on oxidative phosphorylation and oxidative stress.To test these concepts, we have evaluated the effects of CoQ(10, coenzyme Q(2 (CoQ(2, idebenone, and vitamin C on bioenergetics and oxidative stress in human skin fibroblasts with primary CoQ(10 deficiency. A final concentration of 5 microM of each compound was chosen to approximate the plasma concentration of CoQ(10 of patients treated with oral ubiquinone. CoQ(10 supplementation for one week but not for 24 hours doubled ATP levels and ATP/ADP ratio in CoQ(10 deficient fibroblasts therein normalizing the bioenergetics status of the cells. Other compounds did not affect cellular bioenergetics. In COQ2 mutant fibroblasts, increased superoxide anion production and oxidative stress-induced cell death were normalized by all supplements.THESE RESULTS INDICATE THAT: 1 pharmacokinetics of CoQ(10 in reaching the mitochondrial respiratory chain is delayed; 2 short-tail ubiquinone analogs cannot replace CoQ(10 in the mitochondrial respiratory chain under conditions of CoQ(10 deficiency; and 3 oxidative stress and cell death can be counteracted by administration of lipophilic or hydrophilic antioxidants. The results of our in vitro experiments suggest that primary CoQ(10 deficiencies should be treated with CoQ(10 supplementation but not with short-tail ubiquinone analogs, such as idebenone or CoQ(2. Complementary administration of antioxidants with high bioavailability should be considered if oxidative stress is present.

  14. Three-Dimensional Reconstruction, by TEM Tomography, of the Ultrastructural Modifications Occurring in Cucumis sativus L. Mitochondria under Fe Deficiency.

    Directory of Open Access Journals (Sweden)

    Gianpiero Vigani

    Full Text Available Mitochondria, as recently suggested, might be involved in iron sensing and signalling pathways in plant cells. For a better understanding of the role of these organelles in mediating the Fe deficiency responses in plant cells, it is crucial to provide a full overview of their modifications occurring under Fe-limited conditions. The aim of this work is to characterize the ultrastructural as well as the biochemical changes occurring in leaf mitochondria of cucumber (Cucumis sativus L. plants grown under Fe deficiency.Mitochondrial ultrastructure was investigated by transmission electron microscopy (TEM and electron tomography techniques, which allowed a three-dimensional (3D reconstruction of cellular structures. These analyses reveal that mitochondria isolated from cucumber leaves appear in the cristae junction model conformation and that Fe deficiency strongly alters both the number and the volume of cristae. The ultrastructural changes observed in mitochondria isolated from Fe-deficient leaves reflect a metabolic status characterized by a respiratory chain operating at a lower rate (orthodox-like conformation with respect to mitochondria from control leaves.To our knowledge, this is the first report showing a 3D reconstruction of plant mitochondria. Furthermore, these results suggest that a detailed characterization of the link between changes in the ultrastructure and functionality of mitochondria during different nutritional conditions, can provide a successful approach to understand the role of these organelles in the plant response to Fe deficiency.

  15. Fatal heart failure associated with CoQ10 and multiple OXPHOS deficiency in a child with propionic acidemia.

    Science.gov (United States)

    Fragaki, Konstantina; Cano, Aline; Benoist, Jean-François; Rigal, Odile; Chaussenot, Annabelle; Rouzier, Cécile; Bannwarth, Sylvie; Caruba, Céline; Chabrol, Brigitte; Paquis-Flucklinger, Véronique

    2011-05-01

    The role of a secondary respiratory chain deficiency as an additional mechanism to intoxication, leading to development of long-term energy-dependent complications, has been recently suggested in patients with propionic acidemia (PA). We show for the first time a coenzyme Q(10) (CoQ(10)) functional defect accompanied by a multiple organ oxidative phosphorylation (OXPHOS) deficiency in a child who succumbed to acute heart failure in the absence of metabolic stress. Quinone-dependent activities in the liver (complex I+III, complex II+III) were reduced, suggesting a decrease in electron transfer related to the quinone pool. The restoration of complex II+III activity after addition of exogenous ubiquinone to the assay system suggests CoQ(10) deficiency. Nevertheless, we disposed of insufficient material to perform direct measurement of CoQ(10) content in the patient's liver. Death occurred before biochemical diagnosis of OXPHOS deficiency could be made. However, this case highlights the usefulness of rapidly identifying CoQ(10) defects secondary to PA since this OXPHOS disorder has a good treatment response which could improve heart complications or prevent their appearance. Nevertheless, further studies will be necessary to determine whether CoQ(10) treatment can be useful in PA complications linked to CoQ(10) deficiency. Copyright © 2011 © Elsevier B.V. and Mitochondria Research Society. All rights reserved. Published by Elsevier B.V. All rights reserved.

  16. Carrier frequency of a nonsense mutation in the adenosine deaminase (ADA) gene implies a high incidence of ADA-deficient severe combined immunodeficiency (SCID) in Somalia and a single, common haplotype indicates common ancestry

    DEFF Research Database (Denmark)

    Sanchez Sanchez, Juan Jose; Monaghan, Gemma; Børsting, Claus

    2007-01-01

    Inherited adenosine deaminase (ADA) deficiency is a rare metabolic disorder that causes immunodeficiency, varying from severe combined immunodeficiency (SCID) in the majority of cases to a less severe form in a small minority of patients. Five patients of Somali origin from four unrelated families......, with severe ADA-SCID, were registered in the Greater London area. Patients and their parents were investigated for the nonsense mutation Q3X (ADA c7C>T), two missense mutations K80R (ADA c239A>G) and R142Q (ADA c425G>A), and a TAAA repeat located at the 3' end of an Alu element (AluVpA) positioned 1.1 kb...... the frequency may be significantly higher. ADA-SCID may be a frequent immunodeficiency disorder in Somalia, but will be underdiagnosed due to the prevailing socioeconomic and nutritional deprivation....

  17. VLCAD deficiency

    DEFF Research Database (Denmark)

    Boneh, A; Andresen, B S; Gregersen, N

    2006-01-01

    We diagnosed six newborn babies with very long-chain acyl-CoA dehydrogenase deficiency (VLCADD) through newborn screening in three years in Victoria (prevalence rate: 1:31,500). We identified seven known and two new mutations in our patients (2/6 homozygotes; 4/6 compound heterozygotes). Blood...... samples taken at age 48-72 h were diagnostic whereas repeat samples at an older age were normal in 4/6 babies. Urine analysis was normal in 5/5. We conclude that the timing of blood sampling for newborn screening is important and that it is important to perform mutation analysis to avoid false......-negative diagnoses of VLCADD in asymptomatic newborn babies. In view of the emerging genotype-phenotype correlation in this disorder, the information derived from mutational analysis can be helpful in designing the appropriate follow-up and therapeutic regime for these patients....

  18. Carnitine deficiency.

    Science.gov (United States)

    Răşanu, T; Mehedinţi-Hâncu, Mihaela; Alexianu, Marilena; Mehedinţi, T; Gheorghe, Emma; Damian, Irene

    2012-01-01

    We present the case of a female patient, aged 12 years, with fatigability and exertional myalgias, progressively developed within the last two years. Negative family history, as well as negative personal medical history, were found. At physical examination, short stature, proximal muscle weakness and mild hepatomegaly were noted. Urine ketones level was slightly decreased, serum transaminases, creatine kinase and lactate dehydrogenase levels were increased. Electromyographical examination showed a myopathic non-specific pattern. Deltoid muscle biopsy revealed: small, clear vesicles are present on Hematoxylin-Eosin and modified Gömöri trichrome stains; modified Gömöri trichrome stain also revealed muscle fibers (especially type I of muscle fibers) having mild to moderate mitochondrial proliferation (red rim and speckled sarcoplasm). The lipid storage has been well demonstrated by Sudan Black stain, which revealed small lipid droplets in type I muscle fibers. Abnormal internal architecture with a punctate pattern was showed by adenine dinucleotide tetrazolium reductase and succinate dehydrogenase stains. Electron microscopy showed small inter-myofibrillar accumulations of round, amorphous, homogeneous acellular substances that are not membrane bounded. These features indicate that these are neutral fat (lipid) droplets. Subsarcolemmal accumulations of mitochondria were also revealed. The differential diagnosis of this case is discussed, and the up to date general data concerning carnitine deficiency are presented. The aim of our case-report is to emphasize the role of muscle biopsy in carnitine deficiency, as well as to remind the necessity of keeping in mind such metabolic disorders when doing the differential diagnostic of a muscular weakness.

  19. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... Research Home / < Back To Health Topics / Iron-Deficiency Anemia Iron-Deficiency Anemia Leer en español What Is Iron-deficiency anemia ... cases, surgery may be advised. Treatments for Severe Iron-Deficiency Anemia Blood Transfusion If your iron-deficiency anemia is ...

  20. Clinical features and outcome of X-linked lymphoproliferative syndrome type 1 (SAP deficiency) in Japan identified by the combination of flow cytometric assay and genetic analysis.

    Science.gov (United States)

    Kanegane, Hirokazu; Yang, Xi; Zhao, Meina; Yamato, Kazumi; Inoue, Masami; Hamamoto, Kazuko; Kobayashi, Chie; Hosono, Ako; Ito, Yoshikiyo; Nakazawa, Yozo; Terui, Kiminori; Kogawa, Kazuhiro; Ishii, Eiichi; Sumazaki, Ryo; Miyawaki, Toshio

    2012-08-01

    X-linked lymphoproliferative syndrome (XLP) type 1 is a rare immunodeficiency, which is caused by mutations in SH2D1A gene. The prognosis of XLP is very poor, and hematopoietic stem cell transplantation (HSCT) is the only curative therapy. We characterized the clinical features and outcome of Japanese patients with XLP-1. We used a combination of flow cytometric analysis and genetic analysis to identify XLP-1 and reviewed the patient characteristics and survival with HSCT. We identified 33 patients from 21 families with XLP-1 in Japan. Twenty-one of the patients (65%) who did not undergo a transplant died of the disease and complications. Twelve patients underwent HSCT, and 11 of these (92%) survived. We described the clinical characteristics and outcomes of Japanese patients with XLP-1, and HSCT was the only curative therapy for XLP-1. The rapid and accurate diagnosis of XLP with the combination of flow cytometric assay and genetic analysis is important. © 2012 John Wiley & Sons A/S.

  1. Disturbed energy metabolism and muscular dystrophy caused by pure creatine deficiency are reversible by creatine intake

    Science.gov (United States)

    Nabuurs, C I; Choe, C U; Veltien, A; Kan, H E; van Loon, L J C; Rodenburg, R J T; Matschke, J; Wieringa, B; Kemp, G J; Isbrandt, D; Heerschap, A

    2013-01-01

    Creatine (Cr) plays an important role in muscle energy homeostasis by its participation in the ATP–phosphocreatine phosphoryl exchange reaction mediated by creatine kinase. Given that the consequences of Cr depletion are incompletely understood, we assessed the morphological, metabolic and functional consequences of systemic depletion on skeletal muscle in a mouse model with deficiency of l-arginine:glycine amidinotransferase (AGAT−/−), which catalyses the first step of Cr biosynthesis. In vivo magnetic resonance spectroscopy showed a near-complete absence of Cr and phosphocreatine in resting hindlimb muscle of AGAT−/− mice. Compared with wild-type, the inorganic phosphate/β-ATP ratio was increased fourfold, while ATP levels were reduced by nearly half. Activities of proton-pumping respiratory chain enzymes were reduced, whereas F1F0-ATPase activity and overall mitochondrial content were increased. The Cr-deficient AGAT−/− mice had a reduced grip strength and suffered from severe muscle atrophy. Electron microscopy revealed increased amounts of intramyocellular lipid droplets and crystal formation within mitochondria of AGAT−/− muscle fibres. Ischaemia resulted in exacerbation of the decrease of pH and increased glycolytic ATP synthesis. Oral Cr administration led to rapid accumulation in skeletal muscle (faster than in brain) and reversed all the muscle abnormalities, revealing that the condition of the AGAT−/− mice can be switched between Cr deficient and normal simply by dietary manipulation. Systemic creatine depletion results in mitochondrial dysfunction and intracellular energy deficiency, as well as structural and physiological abnormalities. The consequences of AGAT deficiency are more pronounced than those of muscle-specific creatine kinase deficiency, which suggests a multifaceted involvement of creatine in muscle energy homeostasis in addition to its role in the phosphocreatine–creatine kinase system. PMID:23129796

  2. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... To Health Topics / Iron-Deficiency Anemia Iron-Deficiency Anemia What Is Iron-deficiency anemia is a common, ... all types of anemia . Signs and Symptoms of Anemia The most common symptom of all types of ...

  3. Vitamin Deficiency Anemia

    Science.gov (United States)

    ... cancer can interfere with the metabolism of folate. Vitamin B-12 deficiency anemia risk factors include: Lack ... vitamin B-12 deficiency anemia called pernicious anemia. Vitamin C deficiency anemia risk factors include: Smoking. Smoking ...

  4. 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 ...

  5. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... Deficiency Anemia Explore Iron-Deficiency Anemia What Is... CAUSES WHO IS AT RISK SIGNS & SYMPTOMS DIAGNOSIS TREATMENTS ... less hemoglobin than normal. Iron-deficiency anemia can cause fatigue (tiredness), shortness of breath, chest pain, and ...

  6. The myopathic form of coenzyme Q10 deficiency is caused by mutations in the electron-transferring-flavoprotein dehydrogenase (ETFDH) gene

    Science.gov (United States)

    Gempel, Klaus; Topaloglu, Haluk; Talim, Beril; Schneiderat, Peter; Schoser, Benedikt G. H.; Hans, Volkmar H.; Pálmafy, Beatrix; Kale, Gulsev; Tokatli, Aysegul; Quinzii, Catarina; Hirano, Michio; Naini, Ali; DiMauro, Salvatore; Prokisch, Holger; Lochmüller, Hanns; Horvath, Rita

    2014-01-01

    Coenzyme Q10 (CoQ10) deficiency is an autosomal recessive disorder with heterogenous phenotypic manifestations and genetic background. We describe seven patients from five independent families with an isolated myopathic phenotype of CoQ10 deficiency. The clinical, histological and biochemical presentation of our patients was very homogenous. All patients presented with exercise intolerance, fatigue, proximal myopathy and high serum CK. Muscle histology showed lipid accumulation and subtle signs of mitochondrial myopathy. Biochemical measurement of muscle homogenates showed severely decreased activities of respiratory chain complexes I and II +III, while complex IV (COX) was moderately decreased. CoQ10 was significantly decreased in the skeletal muscle of all patients. Tandem mass spectrometry detected multiple acyl-CoA deficiency, leading to the analysis of the electron-transferring-flavoprotein dehydrogenase (ETFDH) gene, previously shown to result in another metabolic disorder, glutaric aciduria type II (GAII). All of our patients carried autosomal recessive mutations in ETFDH, suggesting that ETFDH deficiency leads to a secondary CoQ10 deficiency. Our results indicate that the late-onset form of GAII and the myopathic form of CoQ10 deficiency are allelic diseases. Since this condition is treatable, correct diagnosis is of the utmost importance and should be considered both in children and in adults. We suggest to give patients both CoQ10 and riboflavin supplementation, especially for long-term treatment. PMID:17412732

  7. Cardiofaciocutaneous (CFC) syndrome associated with muscular coenzyme Q10 deficiency.

    Science.gov (United States)

    Aeby, A; Sznajer, Y; Cavé, H; Rebuffat, E; Van Coster, R; Rigal, O; Van Bogaert, P

    2007-10-01

    The cardiofaciocutaneous (CFC) syndrome is characterized by congenital heart defect, developmental delay, peculiar facial appearance with bitemporal constriction, prominent forehead, downslanting palpebral fissures, curly sparse hair and abnormalities of the skin. CFC syndrome phenotypically overlaps with Noonan and Costello syndromes. Mutations of several genes (PTPN11, HRAS, KRAS, BRAF, MEK1 and MEK2), involved in the mitogen-activated protein kinase (MAPK) pathway, have been identified in CFC-Costello-Noonan patients. Coenzyme Q10 (CoQ10), a lipophilic molecule present in all cell membranes, functions as an electron carrier in the mitochondrial respiratory chain, where it transports electrons from complexes I and II to complex III. CoQ10 deficiency is a rare treatable mitochondrial disorder with various neurological (cerebellar ataxia, myopathy, epilepsy, mental retardation) and extraneurological (cardiomyopathy, nephropathy) signs that are responsive to CoQ10 supplementation. We report the case of a 4-year-old girl who presented a CFC syndrome, confirmed by the presence of a pathogenic R257Q BRAF gene mutation, together with a muscular CoQ10 deficiency. Her psychomotor development was severely impaired, hindered by muscular hypotonia and ataxia, both improving remarkably after CoQ10 treatment. This case suggests that there is a functional connection between the MAPK pathway and the mitochondria. This could be through the phosphorylation of a nuclear receptor essential for CoQ10 biosynthesis. Another hypothesis is that K-Ras, one of the proteins composing the MAPK pathway, might be recruited into the mitochondria to promote apoptosis. This case highlights that CoQ10 might contribute to the pathogenesis of CFC syndrome.

  8. [Treatment of middle-aged and aged patients with knee osteoarthritis of yang-deficiency induced cold-damp syndrome by ozone combined Chinese materia medica: a clinical research].

    Science.gov (United States)

    Li, Juan-Hong; Zhou, Li-Xia; Li, Gui-Ying; Cheng, Bin

    2013-04-01

    To observe the clinical efficacy of treating middle-aged and aged patients with knee osteoarthritis (KOA) of yang-deficiency induced cold-damp syndrome (YDICDS) by ozone combined Fugui Gutong Granule (FGG). Using a prospective, randomized controlled clinical trial, 200 KOA patients of YDICDS were randomly assigned to four groups. i.e., the control group (Group A), the Chinese medicine treatment group (Group B), the ozone group (Group C), and the Chinese-r medicine treatment plus ozone group (Group D).Patients in Group A took Voltaren Tablet. Those in Group B took FGG. Those in Group C received ozone injection (10 -18 mL) from knee joint cavity at 25 mg/L, once weekly for 4 weeks in total. Those in Group D received injection from knee joint cavity and took FGG. The therapeutic course for all was one month. The efficacy was assessed using visual analogue scale (VAS) and Western Ontario MacMaster University Osteoarthritis index (WOMAC). The VAS score was obviously lower in Group D than in Group B and Group A at 24 h and 1 week (P FGG had advantages in alleviating joint pain, and improving joint stiffness and daily activities of middle-aged and aged patients with KOA of YDICDS.

  9. Gene expression deregulation in postnatal skeletal muscle of TK2 deficient mice reveals a lower pool of proliferating myogenic progenitor cells.

    Directory of Open Access Journals (Sweden)

    João A Paredes

    Full Text Available Loss of thymidine kinase 2 (TK2 causes a heterogeneous myopathic form of mitochondrial DNA (mtDNA depletion syndrome (MDS in humans that predominantly affects skeletal muscle tissue. In mice, TK2 deficiency also affects several tissues in addition to skeletal muscle, including brain, heart, adipose tissue, kidneys and causes death about 3 weeks after birth. We analysed skeletal muscle and heart muscle tissues of Tk2 knockout mice at postnatal development phase and observed that TK2 deficient pups grew slower and their skeletal muscles appeared significantly underdeveloped, whereas heart was close to normal in size. Both tissues showed mtDNA depletion and mitochondria with altered ultrastructure, as revealed by transmission electron microscopy. Gene expression microarray analysis showed a strong down-regulation of genes involved in cell cycle and cell proliferation in both tissues, suggesting a lower pool of undifferentiated proliferating cells. Analysis of isolated primary myoblasts from Tk2 knockout mice showed slow proliferation, less ability to differentiate and signs of premature senescence, even in absence of mtDNA depletion. Our data demonstrate that TK2 deficiency disturbs myogenic progenitor cells function in postnatal skeletal muscle and we propose this as one of the causes of underdeveloped phenotype and myopathic characteristic of the TK2 deficient mice, in addition to the progressive mtDNA depletion, mitochondrial damage and respiratory chain deficiency in post-mitotic differentiated tissue.

  10. Neonatal liver failure and Leigh syndrome possibly due to CoQ-responsive OXPHOS deficiency.

    Science.gov (United States)

    Leshinsky-Silver, E; Levine, A; Nissenkorn, A; Barash, V; Perach, M; Buzhaker, E; Shahmurov, M; Polak-Charcon, S; Lev, D; Lerman-Sagie, T

    2003-08-01

    CoQ transfers electrons from complexes I and II of the mitochondrial respiratory chain to complex III. There are very few reports on human CoQ deficiency. The clinical presentation is usually characterized by: epilepsy, muscle weakness, ataxia, cerebellar atrophy, migraine, myogloblinuria and developmental delay. We describe a patient who presented with neonatal liver and pancreatic insufficiency, tyrosinemia and hyperammonemia and later developed sensorineural hearing loss and Leigh syndrome. Liver biopsy revealed markedly reduced complex I+III and II+III. Addition of CoQ to the liver homogenate restored the activities, suggesting CoQ depletion. Histological staining showed prominent bridging; septal fibrosis and widening of portal spaces with prominent mixed inflammatory infiltrate, associated with interface hepatitis, bile duct proliferation with numerous bile plugs. Electron microscopy revealed a large number of mitochondria, which were altered in shape and size, widened and disordered intercristal spaces. This may be the first case of Leigh syndrome with liver and pancreas insufficiency, possibly caused by CoQ responsive oxphos deficiency.

  11. Granulocyte colony-stimulating factor recruitment of CD34+ progenitors to peripheral blood: impaired mobilization in chronic granulomatous disease and adenosine deaminase--deficient severe combined immunodeficiency disease patients.

    Science.gov (United States)

    Sekhsaria, S; Fleisher, T A; Vowells, S; Brown, M; Miller, J; Gordon, I; Blaese, R M; Dunbar, C E; Leitman, S; Malech, H L

    1996-08-01

    Peripheral blood (PB) CD34+ cells mobilized by granulocyte colony-stimulating factor (G-CSF) administration are potentially useful for transplantation and as a target of gene transfer for therapy of hematopoietic disorders. Efficient harvest and planning for clinical use of PB CD34+ cells ideally requires foreknowledge of the expected mobilization kinetics and yield. We developed a sensitive flow cytometric assay for accurately enumerating CD34+ cells throughout the range seen at baseline to peak mobilization. We used this assay to assess the kinetics of G-CSF-mediated mobilization of CD34+ cells to PB in normal volunteers and in patients with chronic granulomatous disease (CGD) or adenosine deaminase (ADA)-deficient severe combined immunodeficiency disease (SCID). Two dose levels of G-CSF were examined (5 and 10 micrograms/kg/d for 7 days). Both doses were well tolerated. For normal subjects and patients an increase in PB CD34+ cells was first detected only preceding the third dose of G-CSF (day 3), peaked transiently on day 5 or 6, and then decreased thereafter despite additional doses of G-CSF. With 32 normal volunteers mean peak CD34+ cell counts were 57 and 76 cells/mm2 of blood (5 and 10 micrograms doses, respectively), whereas for 18 CGD patients the mean peaks were 31 and 40 cells/mm2 of blood. For 2 ADA-deficient SCID patients studied at a G-CSF dose of 5 micrograms/kg/d, the average peak was 16 cells/mm2 of blood. For both of these patient groups mobilization of CD34+ cells to PB was impaired compared with similarly treated normal subjects (P 48%. Thus, ANC is not a reliable surrogate to predict peak PB CD34+ cell counts and direct enumeration of PB CD34+ counts should be undertaken in decisions regarding timing and duration of apheresis to harvest a specific number of these cells. Finally, unexpected, but significant differences in the PB CD34+ cell mobilization between normal subjects and patients with inherited disorders can occur and underscores the

  12. Iron-Deficiency Anemia

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    Full Text Available ... less hemoglobin than normal. Iron-deficiency anemia can cause fatigue (tiredness), shortness of breath, chest pain, and ... iron-deficiency anemia. Treatment will depend on the cause and severity of the condition. Treatments may include ...

  13. Iron-Deficiency Anemia

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    Full Text Available ... food. Overview Iron-deficiency anemia is a common type of anemia . The term "anemia" usually refers to ... also may lead to iron-deficiency anemia. This type of blood loss isn't always obvious, and ...

  14. Iron-Deficiency Anemia

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    Full Text Available ... or an inability to absorb enough iron from food. Overview Iron-deficiency anemia is a common type ... of the condition. Treatments may include dietary changes, medicines, and surgery. Severe iron-deficiency anemia may require ...

  15. Iron-Deficiency Anemia

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    Full Text Available ... condition. Women Women of childbearing age are at higher risk for iron-deficiency anemia because of blood ... iron-deficiency anemia. Pregnant women also are at higher risk for the condition because they need twice ...

  16. Iron-Deficiency Anemia

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    Full Text Available ... help prevent overdosing in children. Because recent research supports concerns that iron deficiency during infancy and childhood ... treat iron-deficiency anemia. These doctors include pediatricians, family doctors, gynecologists/obstetricians, and internal medicine specialists. A ...

  17. Iron-Deficiency Anemia

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    Full Text Available ... more information about diet and supplements, go to "How Is Iron-Deficiency Anemia Treated?" Infants and young ... who should be screened for iron deficiency, and how often: Girls aged 12 to 18 and women ...

  18. Iron-Deficiency Anemia

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    Full Text Available ... and other symptoms. Severe iron-deficiency anemia can lead to heart problems, infections, problems with growth and ... Internal bleeding (bleeding inside the body) also may lead to iron-deficiency anemia. This type of blood ...

  19. Iron-Deficiency Anemia

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    Full Text Available ... have iron-deficiency anemia, you'll have a high level of transferrin that has no iron. Other ... may include dietary changes and supplements, medicines, and surgery. Severe iron-deficiency anemia may require a blood ...

  20. Iron-Deficiency Anemia

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    Full Text Available ... deficiency anemia if they're underweight or have chronic (ongoing) illnesses. Teenage girls who have heavy periods ... factors for iron-deficiency anemia The Centers for Disease Control and Prevention (CDC) has developed guidelines for ...

  1. Iron-Deficiency Anemia

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    Full Text Available ... deficiency anemia apply to all types of anemia . Signs and Symptoms of Anemia The most common symptom ... appetite, slowed growth and development, and behavioral problems. Signs and Symptoms of Iron Deficiency Signs and symptoms ...

  2. Iron-Deficiency Anemia

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    Full Text Available ... also may help treat iron-deficiency anemia. Medical History Your doctor will ask about your signs and ... much of the transferrin in your blood isn't carrying iron. If you have iron-deficiency anemia, ...

  3. Iron-Deficiency Anemia

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    Full Text Available ... coped with having iron-deficiency anemia. Prior to her diagnosis, Susan had symptoms such as tiredness, poor skin tone, dizziness, and depression. After her doctor diagnosed her with iron-deficiency anemia, Susan ...

  4. Iron-Deficiency Anemia

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    Full Text Available ... drawings also can cause iron-deficiency anemia. Poor Diet The best sources of iron are meat, poultry, ... more likely to develop iron-deficiency anemia. Vegetarian diets can provide enough iron if you eat the ...

  5. Iron-Deficiency Anemia

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    Full Text Available ... Deficiency Anemia What Is... CAUSES WHO IS AT RISK SIGNS & SYMPTOMS DIAGNOSIS TREATMENTS PREVENTION LIVING WITH CLINICAL ... and women are the two groups at highest risk for iron-deficiency anemia. Outlook Doctors usually can ...

  6. Iron-Deficiency Anemia

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    Full Text Available ... iron-deficiency anemia may require treatment in a hospital, blood transfusions , iron injections, or intravenous iron therapy. ... Treatment may need to be done in a hospital. The goals of treating iron-deficiency anemia are ...

  7. The Combined Deficiency of Immunoproteasome Subunits Affects Both the Magnitude and Quality of Pathogen- and Genetic Vaccination-Induced CD8+ T Cell Responses to the Human Protozoan Parasite Trypanosoma cruzi.

    Directory of Open Access Journals (Sweden)

    Jonatan Ersching

    2016-04-01

    Full Text Available The β1i, β2i and β5i immunoproteasome subunits have an important role in defining the repertoire of MHC class I-restricted epitopes. However, the impact of combined deficiency of the three immunoproteasome subunits in the development of protective immunity to intracellular pathogens has not been investigated. Here, we demonstrate that immunoproteasomes play a key role in host resistance and genetic vaccination-induced protection against the human pathogen Trypanosoma cruzi (the causative agent of Chagas disease, immunity to which is dependent on CD8+ T cells and IFN-γ (the classical immunoproteasome inducer. We observed that infection with T. cruzi triggers the transcription of immunoproteasome genes, both in mice and humans. Importantly, genetically vaccinated or T. cruzi-infected β1i, β2i and β5i triple knockout (TKO mice presented significantly lower frequencies and numbers of splenic CD8+ effector T cells (CD8+CD44highCD62Llow specific for the previously characterized immunodominant (VNHRFTLV H-2Kb-restricted T. cruzi epitope. Not only the quantity, but also the quality of parasite-specific CD8+ T cell responses was altered in TKO mice. Hence, the frequency of double-positive (IFN-γ+/TNF+ or single-positive (IFN-γ+ cells specific for the H-2Kb-restricted immunodominant as well as subdominant T. cruzi epitopes were higher in WT mice, whereas TNF single-positive cells prevailed among CD8+ T cells from TKO mice. Contrasting with their WT counterparts, TKO animals were also lethally susceptible to T. cruzi challenge, even after an otherwise protective vaccination with DNA and adenoviral vectors. We conclude that the immunoproteasome subunits are key determinants in host resistance to T. cruzi infection by influencing both the magnitude and quality of CD8+ T cell responses.

  8. Iron-Deficiency Anemia

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    Full Text Available ... To Health Topics / Iron-Deficiency Anemia Iron-Deficiency Anemia Leer en español What Is Iron-deficiency anemia ... all types of anemia . Signs and Symptoms of Anemia The most common symptom of all types of ...

  9. Iron-Deficiency Anemia

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    Full Text Available ... page from the NHLBI on Twitter. What Is Iron-Deficiency Anemia? Español Iron-deficiency anemia is a ... Content: NEXT >> Featured Video Living With and Managing Iron-Deficiency Anemia 05/18/2011 This video—presented ...

  10. Iron-Deficiency Anemia

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    Full Text Available ... Tumblr. Share this page from the NHLBI on Twitter. What Is Iron-Deficiency Anemia? Español Iron-deficiency ... Iron-Deficiency Anemia article. Updated: March 26, 2014 Twitter Facebook YouTube Google+ SITE INDEX ACCESSIBILITY PRIVACY STATEMENT ...

  11. Iron-Deficiency Anemia

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    Full Text Available ... the NHLBI on Twitter. What Is Iron-Deficiency Anemia? Español Iron-deficiency anemia is a common, easily ... Featured Video Living With and Managing Iron-Deficiency Anemia 05/18/2011 This video—presented by the ...

  12. Iron-Deficiency Anemia

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    Full Text Available ... iron-deficiency anemia, especially if they have: A history of iron-deficiency anemia Heavy blood loss during their monthly periods Other risk factors for iron-deficiency anemia The Centers for Disease Control and Prevention (CDC) has developed guidelines for who ...

  13. 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.

  14. Glucose-6-phosphatase deficiency

    Directory of Open Access Journals (Sweden)

    Labrune Philippe

    2011-05-01

    commonly confirmed by G6PC (GSDIa or SLC37A4 (GSDIb gene analysis, and the indications of liver biopsy to measure G6P activity are getting rarer and rarer. Differential diagnoses include the other GSDs, in particular type III (see this term. However, in GSDIII, glycemia and lactacidemia are high after a meal and low after a fast period (often with a later occurrence than that of type I. Primary liver tumors and Pepper syndrome (hepatic metastases of neuroblastoma may be evoked but are easily ruled out through clinical and ultrasound data. Antenatal diagnosis is possible through molecular analysis of amniocytes or chorionic villous cells. Pre-implantatory genetic diagnosis may also be discussed. Genetic counseling should be offered to patients and their families. The dietary treatment aims at avoiding hypoglycemia (frequent meals, nocturnal enteral feeding through a nasogastric tube, and later oral addition of uncooked starch and acidosis (restricted fructose and galactose intake. Liver transplantation, performed on the basis of poor metabolic control and/or hepatocarcinoma, corrects hypoglycemia, but renal involvement may continue to progress and neutropenia is not always corrected in type Ib. Kidney transplantation can be performed in case of severe renal insufficiency. Combined liver-kidney grafts have been performed in a few cases. Prognosis is usually good: late hepatic and renal complications may occur, however, with adapted management, patients have almost normal life span. Disease name and synonyms Glucose-6-phosphatase deficiency or G6P deficiency or glycogen storage disease type I or GSDI or type I glycogenosis or Von Gierke disease or Hepatorenal glycogenosis.

  15. Beta-Ketothiolase Deficiency

    Directory of Open Access Journals (Sweden)

    Elsayed Abdelkreem MD, MSc

    2016-03-01

    Full Text Available Beta-ketothiolase deficiency is an inherited disorder of ketone body metabolism and isoleucine catabolism. It typically manifests as recurrent ketoacidotic episodes with characteristic abnormalities in the urinary organic acid profile. However, several challenges in the diagnosis of beta-ketothiolase deficiency have been encountered: atypical presentations have been reported and some other disorders, such as succinyl-CoA:3-oxoacid CoA transferase and 2-methyl-3-hydroxybutyryl-CoA dehydrogenase deficiencies, can mimic the clinical and/or biochemical signs of beta-ketothiolase deficiency. A final diagnosis of beta-ketothiolase deficiency requires an enzymatic assay and/or a molecular analysis, but some caveats must be considered. Despite the reported missed cases, screening programs have successfully identified an increasing number of patients with beta-ketothiolase deficiency. Early diagnosis and management of beta-ketothiolase deficiency will enable prevention of its serious acute and chronic complications and ultimately improve the prognosis.

  16. Iron deficiency in cancer patients

    Directory of Open Access Journals (Sweden)

    Flávio Augusto Naoum

    Full Text Available ABSTRACT Anemia is a frequent complication in cancer patients, both at diagnosis and during treatment, with a multifactorial etiology in most cases. Iron deficiency is among the most common causes of anemia in this setting and can develop in nearly half of patients with solid tumors and hematologic malignancies. Surprisingly, this fact is usually neglected by the attending physician in a way that proper and prompt investigation of the iron status is either not performed or postponed. In cancer patients, functional iron deficiency is the predominant mechanism, in which iron availability is reduced due to disease or the therapy-related inflammatory process. Hence, serum ferritin is not reliable in detecting iron deficiency in this setting, whereas transferrin saturation seems more appropriate for this purpose. Besides, lack of bioavailable iron can be further worsened by the use of erythropoiesis stimulating agents that increase iron utilization in the bone marrow. Iron deficiency can cause anemia or worsen pre-existing anemia, leading to a decline in performance status and adherence to treatment, with possible implications in clinical outcome. Due to its frequency and importance, treatment of this condition is already recommended in many specialty guidelines and should be performed preferably with intravenous iron. The evidences regarding the efficacy of this treatment are solid, with response gain when combined with erythropoiesis stimulating agents and significant increments in hemoglobin as monotherapy. Among intravenous iron formulations, slow release preparations present more favorable pharmacological characteristics and efficacy in cancer patients.

  17. Characterization of the respiratory chain of Helicobacter pylori

    DEFF Research Database (Denmark)

    Chen, M; Andersen, L P; Zhai, L

    1999-01-01

    reductase was inhibited by antimycin, implying the presence of a classical pathway from complex II to complex III in this bacterium. The presence of NADH-fumarate reductase (FRD) was demonstrated in H. pylori and fumarate could reduce H2O2 production from NADH, indicating fumarate to be an endogenous...

  18. The respiratory chain of blue-green algae (cyanobacteria).

    Science.gov (United States)

    Peschek, G. A.; Obinger, C.; Paumann, M.

    2004-03-01

    Electron transport components on the way from reduced substrates to the terminal respiratory oxidase(s) are discussed in relation to analogous and/or homologous enzymes and electron carriers in the generally much better known bacteria, mitochondria and chloroplasts. The kinetic behaviour of the components, their localization within the cell and their evolutionary position are given special attention. Pertinent results from molecular genetics are also mentioned. The unprecedented role of cyanobacteria for our biosphere and our whole planet earth appears to deserve a more extended introductory chapter.

  19. Computing sleep deficiency.

    Science.gov (United States)

    Erren, Thomas C; Groß, J Valerie; Lewis, Philip

    2017-11-20

    Sleep deficiency is a major public health concern. Since epidemiological studies play an important role in public health evaluations, this theoretical paper pursues answers to the question: 'How can we compute sleep deficiency as informative measures of exposures or doses in observational research?' Starting from the social jetlag concept and based on the chronodisruption rationale, we illustrate and discuss five approaches (one established and four untested, each with unique strengths and limitations) to quantify sleep deficiency by focusing on the timing and duration of sleep. Hitherto, social jetlag and chronodisruption rationale were neither explicitly proposed nor developed as assessments of sleep deficiency but, as we suggest, could potentially be utilized to this end. This first foray into computing sleep deficiency in epidemiological studies makes clear that laboratory, field and epidemiological collaboration is pre-requisite to elucidating potential (co-)causal roles of sleep deficiency in disease endpoints. © 2017 European Sleep Research Society.

  20. Acquired color vision deficiency.

    Science.gov (United States)

    Simunovic, Matthew P

    2016-01-01

    Acquired color vision deficiency occurs as the result of ocular, neurologic, or systemic disease. A wide array of conditions may affect color vision, ranging from diseases of the ocular media through to pathology of the visual cortex. Traditionally, acquired color vision deficiency is considered a separate entity from congenital color vision deficiency, although emerging clinical and molecular genetic data would suggest a degree of overlap. We review the pathophysiology of acquired color vision deficiency, the data on its prevalence, theories for the preponderance of acquired S-mechanism (or tritan) deficiency, and discuss tests of color vision. We also briefly review the types of color vision deficiencies encountered in ocular disease, with an emphasis placed on larger or more detailed clinical investigations. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Manganese deficiency in plants

    DEFF Research Database (Denmark)

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

    2016-01-01

    restricting crop productivity in many places of the world. Hence, timely alleviation of latent Mn deficiency is a challenge in promoting plant growth and quality. We describe here the key mechanisms of Mn deficiency in plants by focusing on the impact of Mn on PSII stability and functionality. We also address...... the mechanisms underlying the differential tolerance towards Mn deficiency observed among plant genotypes, which enable Mn-efficient plants to grow on marginal land with poor Mn availability....

  2. Integrated analysis of the involvement of nitric oxide synthesis in mitochondrial proliferation, mitochondrial deficiency and apoptosis in skeletal muscle fibres

    Science.gov (United States)

    Rodrigues, Gabriela Silva; Godinho, Rosely Oliveira; Kiyomoto, Beatriz Hitomi; Gamba, Juliana; Oliveira, Acary Souza Bulle; Schmidt, Beny; Tengan, Célia Harumi

    2016-01-01

    Nitric oxide (NO) is an important signaling messenger involved in different mitochondrial processes but only few studies explored the participation of NO in mitochondrial abnormalities found in patients with genetic mitochondrial deficiencies. In this study we verified whether NO synthase (NOS) activity was altered in different types of mitochondrial abnormalities and whether changes in mitochondrial function and NOS activity could be associated with the induction of apoptosis. We performed a quantitative and integrated analysis of NOS activity in individual muscle fibres of patients with mitochondrial diseases, considering mitochondrial function (cytochrome-c-oxidase activity), mitochondrial content, mitochondrial DNA mutation and presence of apoptotic nuclei. Our results indicated that sarcolemmal NOS activity was increased in muscle fibres with mitochondrial proliferation, supporting the relevance of neuronal NOS in the mitochondrial biogenesis process. Sarcoplasmic NOS activity was reduced in cytochrome-c-oxidase deficient fibres, probably as a consequence of the involvement of NO in the regulation of the respiratory chain. Alterations in NOS activity or mitochondrial abnormalities were not predisposing factors to apoptotic nuclei. Taken together, our results show that NO can be considered a potential molecular target for strategies to increase mitochondrial content and indicate that this approach may not be associated with increased apoptotic events. PMID:26856437

  3. Peculiarities of the free radical processes in rat liver mitochondria under toxic hepatitis on the background of alimentary protein deficiency

    Directory of Open Access Journals (Sweden)

    G. P. Kopylchuk

    2016-04-01

    Full Text Available The rate of superoxide anion radical, hydroxyl radical and hydrogen peroxide generation, the level of oxidative modification of mitochondrial proteins in the liver of rats with toxic hepatitis was investigated on the background of alimentary protein deficiency. We did not find significant increases of the intensity of free radical processes in liver mitochondria of rats maintained on the protein-deficient ration. The most significant intensification of free radical processes in liver mitochondria is observed under the conditions of toxic hepatitis, induced on the background of alimentary protein deprivation. Under these conditions the aggravation of all studied forms of reactive oxygen species generation was observed in liver mitochondria. The generation rates were increased as follows: O2 – by 1.7 times, Н2О2 – by 1.5 times, •ОН – practically double on the background of accumulation of oxidized mitochondria-derived proteins. The established changes in thiol groups’ redox status of respiratory chain proteins insoluble in 0.05 M sodium-phosphate buffer (pH 11.5, and changes of their carbonyl derivatives content may be considered as one of the regulatory factors of mitochondrial energy-generating function.

  4. Refractory epilepsy and mitochondrial dysfunction due to GM3 synthase deficiency.

    Science.gov (United States)

    Fragaki, Konstantina; Ait-El-Mkadem, Samira; Chaussenot, Annabelle; Gire, Catherine; Mengual, Raymond; Bonesso, Laurent; Bénéteau, Marie; Ricci, Jean-Ehrland; Desquiret-Dumas, Valérie; Procaccio, Vincent; Rötig, Agnès; Paquis-Flucklinger, Véronique

    2013-05-01

    We report two children, born from consanguineous parents, who presented with early-onset refractory epilepsy associated with psychomotor delay, failure to thrive, blindness and deafness. Polarographic and spectrophotometric analyses in fibroblasts and liver revealed a respiratory chain (RC) dysfunction. Surprisingly, we identified a homozygous nonsense mutation in the GM3 synthase gene by using exome sequencing. GM3 synthase catalyzes the formation of GM3 ganglioside from lactosylceramide, which is the first step in the synthesis of complex ganglioside species. Mass spectrometry analysis revealed that the complete absence of GM3 ganglioside and its biosynthetic derivatives was associated with an upregulation of the alternative globoside pathway in fibroblasts. The accumulation of Gb3 and Gb4 globosides likely has a role in RC dysfunction and in the decrease of mitochondrial membrane potential leading to apoptosis, which we observed in fibroblasts. We show for the first time that GM3 synthase deficiency, responsible for early-onset epilepsy syndrome, leads to a secondary RC dysfunction. Our study highlights the role of secondary mitochondrial disorders that can interfere with the diagnosis and the evolution of other metabolic diseases.

  5. Vitamin D deficiency in Europe

    DEFF Research Database (Denmark)

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

    2016-01-01

    25(OH)D values from national health/nutrition surveys. OBJECTIVE: This study applied VDSP protocols to serum 25(OH)D data from representative childhood/teenage and adult/older adult European populations, representing a sizable geographical footprint, to better quantify the prevalence of vitamin D......BACKGROUND: Vitamin D deficiency has been described as being pandemic, but serum 25-hydroxyvitamin D [25(OH)D] distribution data for the European Union are of very variable quality. The NIH-led international Vitamin D Standardization Program (VDSP) has developed protocols for standardizing existing...... sera. These data were combined with standardized serum 25(OH)D data from 4 previously standardized studies (for a total n = 55,844). Prevalence estimates of vitamin D deficiency [using various serum 25(OH)D thresholds] were generated on the basis of standardized 25(OH)D data. RESULTS: An overall pooled...

  6. IgA deficiency: clinical correlates with IgG subclass and mannan-binding lectin deficiencies.

    Science.gov (United States)

    Santaella, María L; Peredo, Rubén; Disdier, Orville M

    2005-06-01

    To characterize an IgA deficient population in terms of the incidence of IgG subclass and mannose-binding lectin (MBL) deficiencies and the type and severity of infections and other associated disorders. Selective IgA deficiency is probably the commonest of the primary immunodeficiency disorders and although it may lead to an increased risk for respiratory and gastrointestinal infections and associated to various autoimmune diseases, it may also be asymptomatic. Several studies have suggested the need of a concomitant defect in order for manifestation of its symptoms. A total of 27 patients fulfilling the diagnostic criteria of selective IgA deficiency were evaluated for IgG subclass and MBL deficiencies after a thorough medical history, physical examination and pertinent evaluation for concomitant medical conditions. The overall incidence of IgG subclass deficiency found in the IgA deficient group was 18.5%. MBL deficiency was found to be 3.7%. These frequencies may have been influenced by the age group evaluated and the size of the population studied. Severe infections were more common in patients with combined deficiencies, either IgA and any of the IgG subclasses or IgA and MBL deficiency. Atopy was widely represented in the patients studied. The observed relationship between combined deficiencies Ig A, IgG subclasses and MBL and the increased representation of severe infections needs to be corroborated in a larger sample of patients with an inclusion of pediatric patients.

  7. Down-Syndrome associated with MBL-deficiency, IgG-deficiency, vasculitis and mutated prothrombin.

    Science.gov (United States)

    Wolf, Hermann M; Stöllberger, Claudia; Finsterer, Josef

    2009-01-01

    The association of Down syndrome with mannose-binding lectin (MBL)-deficiency, recurrent infections and vasculitis has not been reported. We report a 30 year-old female with Down-syndrome associated with MBL-deficiency with the genotype LXA/HYD, IgG-deficiency, recurrent uro-genital infections, cutaneous vasculitis, G20.210A prothrombin mutation, deep venous thrombosis, and pulmonary embolism. MBL-deficiency in combination with IgG deficiency might have favored the development of recurrent uro-genital infections. Immunodeficiency might be also involved in the pathogenesis of cutaneous vasculitis. Deep venous thrombosis and pulmonary embolism were attributed to the genetically determined prothrombotic state and intake of oral contraceptives.

  8. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... diet. Young children who drink a lot of cow's milk may be at risk for iron-deficiency anemia. ... her risk for iron-deficiency anemia. For example, cow's milk is low in iron. For this and other ...

  9. Serine-deficiency syndromes

    NARCIS (Netherlands)

    de Koning, Tom J; Klomp, Leo W J

    PURPOSE OF REVIEW: Serine-deficiency disorders comprise a new group of neurometabolic diseases and are caused by defects in the biosynthesis of the amino acid L-serine. In contrast to most neurometabolic disorders, serine-deficiency disorders are potentially treatable. Furthermore, the severe

  10. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... Organization NHLBI Director Budget, Planning, & Legislative Advisory Committees Jobs Contact Us FAQs Home » Iron-Deficiency Anemia Explore ... the body. Iron-deficiency anemia usually develops over time if your body doesn't have enough iron ...

  11. Iron deficiency anemia

    Science.gov (United States)

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

  12. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... have enough iron stored in your body to make up for the lost iron, you'll develop iron- ... by mouth. This therapy also is given to people who need immediate treatment for iron-deficiency ... have iron-deficiency anemia, get ongoing care to make sure your iron levels are improving. At your ...

  13. 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)....

  14. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... Blood Tests Blood Transfusion Restless Legs Syndrome Send a link to NHLBI to someone by E-MAIL | ... Iron-Deficiency Anemia? Español Iron-deficiency anemia is a common, easily treated condition that occurs if you ...

  15. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... shows how Susan, a full-time worker and student, has coped with having iron-deficiency anemia. Prior to her diagnosis, Susan had symptoms such as tiredness, poor skin tone, dizziness, and depression. After her doctor diagnosed her with iron-deficiency ...

  16. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... For more information about diet and supplements, go to "How Is Iron-Deficiency Anemia Treated?" Infants and young ... who should be screened for iron deficiency, and how often: Girls aged 12 to 18 and women of childbearing age who are ...

  17. Nutritional iron deficiency

    NARCIS (Netherlands)

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

    2007-01-01

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

  18. Alpha1-antitrypsin deficiency

    DEFF Research Database (Denmark)

    Stolk, Jan; Seersholm, Niels; Kalsheker, Noor

    2006-01-01

    deficiency and contributes to an international database located in Malmö, Sweden. This database is designed to increase understanding of AAT deficiency. Additionally, AIR members are engaged in active, wide-ranging investigations to improve the diagnosis, monitoring, and treatment of the disease and meet...

  19. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... women of childbearing age has iron-deficiency anemia. Pregnant women also are at higher risk for the condition ... for the fetus' growth. About half of all pregnant women develop iron-deficiency anemia. The condition can increase ...

  20. Maternal vitamin D deficiency

    African Journals Online (AJOL)

    GB

    2017-05-01

    May 1, 2017 ... ABSTRACT. BACKGROUND: A rare but reversible cause of dilated cardiomyopathy occurs in infants born to vitamin D deficient mothers due to hypocalcaemia. CASE REPORT: We report a case of dilated cardiomyopathy due to hypocalcaemia secondary to maternal vitamin D deficiency in an.

  1. G6PD Deficiency

    Science.gov (United States)

    Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a genetic disorder that is most common in males. About 1 in 10 African American males in the United States has it. G6PD deficiency mainly affects red blood cells, which carry oxygen ...

  2. Iron deficiency in childhood

    NARCIS (Netherlands)

    Uijterschout, L.

    2015-01-01

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

  3. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... have RLS often have a hard time sleeping. Iron-deficiency anemia can put children at greater risk for lead poisoning and infections. Some signs and symptoms of iron-deficiency anemia are related to the condition's causes. For ...

  4. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... food. Overview Iron-deficiency anemia is a common type of anemia . The term "anemia" usually refers to a condition ... symptoms of iron-deficiency anemia apply to all types of anemia . Signs and Symptoms of Anemia The most common ...

  5. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... will diagnose iron-deficiency anemia based on your medical history, a physical exam, and the results from tests and procedures. Once ... specialists also may help treat iron-deficiency anemia. Medical ... be pregnant. Physical Exam Your doctor will do a physical exam to ...

  6. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... be advised. Treatments for Severe Iron-Deficiency Anemia Blood Transfusion If your iron-deficiency anemia is severe, you ... get a transfusion of red blood cells. A blood transfusion is a safe, common procedure in which blood ...

  7. Vitamin D recommendations: beyond deficiency.

    Science.gov (United States)

    Biesalski, Hans K

    2011-01-01

    Vitamin D plays an important role in regular bone growth and in adequate function of the innate immune system, including barrier functions of mucous membranes. A sufficient supply during pregnancy and lactation protects the child from infectious diseases. Clinical symptoms of severe vitamin D deficiency (rickets) are well known and can be easily detected. Signs and symptoms beyond deficiency, however, remain to be elucidated. Based on clinical and observational data, the plasma level of 25(OH)D may serve as a 'marker' to detect or define a subclinical deficiency. Levels below 50 nmol/l might be insufficient to maintain the non-bone-related activities of vitamin D. Finally, it has to be considered that all of the nonbone activities of vitamin D are in concert with vitamin A (9-cis retinoic acid). Studies combining both vitamins in sufficient amounts (cod liver oil) demonstrated a beneficial effect on the prevention of respiratory tract infections. Consequently, it should be strongly recommended to increase the intake of vitamin D and to ensure a daily intake of vitamin A as counseled. Copyright © 2011 S. Karger AG, Basel.

  8. Infantile Galactosialidosis Associated With Vitamin D Deficiency Rickets

    OpenAIRE

    BODUROĞLU, Koray

    2014-01-01

    Galactosialidosis is an autosomal recessive disease with combined deficiency of two lysosomal enzymes due to the lack of a protective protein. We report on a boy with infantile galactosialidosis who has an intermediate phenotype and vitamin D deficiency rickets. Due to the possible role of vitamin D deficiency in the pathogenesis of dysostosis multiplex we recommend that patients with lysosomal storage disease should be supplemented with vitamin D.

  9. Iron deficiency in cancer patients.

    Science.gov (United States)

    Naoum, Flávio Augusto

    Anemia is a frequent complication in cancer patients, both at diagnosis and during treatment, with a multifactorial etiology in most cases. Iron deficiency is among the most common causes of anemia in this setting and can develop in nearly half of patients with solid tumors and hematologic malignancies. Surprisingly, this fact is usually neglected by the attending physician in a way that proper and prompt investigation of the iron status is either not performed or postponed. In cancer patients, functional iron deficiency is the predominant mechanism, in which iron availability is reduced due to disease or the therapy-related inflammatory process. Hence, serum ferritin is not reliable in detecting iron deficiency in this setting, whereas transferrin saturation seems more appropriate for this purpose. Besides, lack of bioavailable iron can be further worsened by the use of erythropoiesis stimulating agents that increase iron utilization in the bone marrow. Iron deficiency can cause anemia or worsen pre-existing anemia, leading to a decline in performance status and adherence to treatment, with possible implications in clinical outcome. Due to its frequency and importance, treatment of this condition is already recommended in many specialty guidelines and should be performed preferably with intravenous iron. The evidences regarding the efficacy of this treatment are solid, with response gain when combined with erythropoiesis stimulating agents and significant increments in hemoglobin as monotherapy. Among intravenous iron formulations, slow release preparations present more favorable pharmacological characteristics and efficacy in cancer patients. Copyright © 2016 Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular. Published by Elsevier Editora Ltda. All rights reserved.

  10. 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

  11. Acute psychosis: a presentation of cyanocobalamin deficiency megaloblastic anemia.

    Science.gov (United States)

    Tripathi, A K; Verma, S P; Himanshu, D

    2010-09-01

    Cyanocobalamin deficiency is not rare in India. Patients present with megaloblastic anemia, pancytopenia and sometimes neuropsychiatric manifestations. Subacute combined degeneration of the cord, peripheral neuropathy, dementia, psychotic depression and paranoid schizophrenia are well reported. We are reporting a case of cyanocobalamine deficiency anemia who presented with acute psychosis which readily reversed on cyanocobalamin replacement.

  12. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... bleeding. Other At-Risk Groups People who get kidney dialysis treatment may develop iron-deficiency anemia. This ... because blood is lost during dialysis. Also, the kidneys are no longer able to make enough of ...

  13. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... if you have intestinal surgery (such as gastric bypass) or a disease of the intestine (such as ... produce red blood cells. People who have gastric bypass surgery also may develop iron-deficiency anemia. This ...

  14. 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, ... symptoms. Severe iron-deficiency anemia can lead to heart problems, infections, problems with growth and development in ...

  15. Iron-Deficiency Anemia

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    Full Text Available ... NHLBI About NHLBI Home Mission and Strategic Vision Leadership Scientific Divisions Operations and Administration Advisory Committees Budget ... include poor appetite, slowed growth and development, and behavioral problems. Signs and Symptoms of Iron Deficiency Signs ...

  16. Iron-Deficiency Anemia

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    Full Text Available ... also may help treat iron-deficiency anemia. Medical History Your doctor will ask about your signs and ... It must be done in a hospital or clinic by experienced staff. Iron therapy usually is given ...

  17. Iron-Deficiency Anemia

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    Full Text Available ... re more likely to develop iron-deficiency anemia. Vegetarian diets can provide enough iron if you eat ... which are the best sources of iron. However, vegetarian diets can provide enough iron if you eat ...

  18. Iron-Deficiency Anemia

    Science.gov (United States)

    ... re more likely to develop iron-deficiency anemia. Vegetarian diets can provide enough iron if you eat ... which are the best sources of iron. However, vegetarian diets can provide enough iron if you eat ...

  19. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... a waste product) from your body. Anemia also can occur if your red blood cells don't ... have less hemoglobin than normal. Iron-deficiency anemia can cause fatigue (tiredness), shortness of breath, chest pain, ...

  20. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... usually can successfully treat iron-deficiency anemia. Treatment will depend on the cause and severity of the ... about a healthy diet and food choices that will help your child get enough iron. Your child's ...

  1. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... or soil, or drinking water that contains lead. Teens Teens are at risk for iron-deficiency anemia if ... and bleeding ulcers, can cause blood loss. Some medicines, such as aspirin, also can cause internal bleeding. ...

  2. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... or soil, or drinking water that contains lead. Teens Teens are at risk for iron-deficiency anemia ... for increased blood volume and for the fetus' growth. About half of all pregnant women develop iron- ...

  3. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... anemia at 1 year of age. Women and Girls Women of childbearing age may be tested for ... be screened for iron deficiency, and how often: Girls aged 12 to 18 and women of childbearing ...

  4. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... condition. Treatments may include dietary changes, medicines, and surgery. Severe iron-deficiency anemia may require treatment in ... Urinary tract bleeding Blood loss from severe injuries, surgery, or frequent blood drawings also can cause iron- ...

  5. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... or soil, or drinking water that contains lead. Teens Teens are at risk for iron-deficiency anemia if ... Visit Children and Clinical Studies to hear experts, parents, and children talk about their experiences with clinical ...

  6. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... symptoms. Severe iron-deficiency anemia can lead to heart problems, infections, problems with growth and development in ... 18/2011 This video—presented by the National Heart, Lung, and Blood Institute, part of the National ...

  7. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... Digg. Share this page from the NHLBI on Facebook. Add this link to the NHLBI to my ... Deficiency Anemia article. Updated: March 26, 2014 Twitter Facebook YouTube Google+ SITE INDEX ACCESSIBILITY PRIVACY STATEMENT FOIA ...

  8. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... and Blood Safety Sleep Science and Sleep Disorders Lung Diseases Heart and Vascular Diseases Precision Medicine Activities ... iron-rich protein that carries oxygen from the lungs to the rest of the body. Iron-deficiency ...

  9. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... leafy green vegetables like turnip greens and spinach. Treatment To Stop Bleeding If blood loss is causing ... flow. In some cases, surgery may be advised. Treatments for Severe Iron-Deficiency Anemia Blood Transfusion If ...

  10. Alpha-1 Antitrypsin Deficiency

    Science.gov (United States)

    ... seafood, processed soy products, nuts, seeds, beans, and peas. A healthy diet is low in sodium (salt), ... help you cope with stress. Emotional Issues and Support Living with AAT deficiency may cause fear, anxiety, ...

  11. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... Disorders Lung Diseases Heart and Vascular Diseases Precision Medicine Activities Obesity, Nutrition, and Physical Activity Population and ... of the condition. Treatments may include dietary changes, medicines, and surgery. Severe iron-deficiency anemia may require ...

  12. Vitamin D Deficiency

    Science.gov (United States)

    ... disease osteoporosis. Severe vitamin D deficiency can cause rickets in children and osteomalacia in adults. Both problems cause soft, ... The oral dose is once daily or weekly. Children with rickets or at risk of this disease may get ...

  13. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... need to be done in a hospital. The goals of treating iron-deficiency anemia are to treat ... and children talk about their experiences with clinical research. More Information Related Health Topics Anemia Blood Tests ...

  14. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... low iron levels in women. Internal bleeding (bleeding inside the body) also may lead to iron-deficiency ... a diagnosis, look for a cause, and find out how severe the condition is. Complete Blood Count ...

  15. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... the body. Iron-deficiency anemia usually develops over time if your body doesn't have enough iron ... because your need for iron increases during these times of growth and development. Inability To Absorb Enough ...

  16. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... People who have RLS often have a hard time sleeping. Iron-deficiency anemia can put children at ... Reticulocytes are young, immature red blood cells. Over time, reticulocytes become mature red blood cells that carry ...

  17. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... or iron supplements, when used properly, can help prevent iron-deficiency anemia in infants and young children. ... in the diet. Too much milk also may prevent children's bodies from absorbing iron from other foods. ...

  18. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... Health Topics Education & Awareness Resources Contact The Health Information Center Health Professionals Systematic Evidence Reviews & Clinical Practice ... and see the benefits of treatment. For more information about living with and managing iron-deficiency anemia, ...

  19. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... the cause and severity of the condition. Treatments may include dietary changes, medicines, and surgery. Severe iron-deficiency anemia may require treatment in a hospital, blood transfusions , iron ...

  20. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... the first prenatal visit. For pregnant women, medical care during pregnancy usually includes screening for anemia. Also, ... while checking for other problems. Specialists Involved Primary care doctors often diagnose and treat iron-deficiency anemia. ...

  1. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... green leafy vegetables. Eat poorly because of money, social, health, or other problems. Follow a very low- ... help prevent overdosing in children. Because recent research supports concerns that iron deficiency during infancy and childhood ...

  2. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... hemoglobin than normal. Iron-deficiency anemia can cause fatigue (tiredness), shortness of breath, chest pain, and other ... common symptom of all types of anemia is fatigue (tiredness). Fatigue occurs because your body doesn't ...

  3. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... treat iron-deficiency anemia. These doctors include pediatricians, family doctors, gynecologists/obstetricians, and internal medicine specialists. A ... Center for Health Information Email Alerts Jobs and Careers Site Index About NHLBI National Institute of Health ...

  4. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... Follow a very low-fat diet over a long time. Some higher fat foods, like meat, are ... iron deficiency during infancy and childhood can have long-lasting, negative effects on brain health, the American ...

  5. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... Anemia What Is... CAUSES WHO IS AT RISK SIGNS & SYMPTOMS DIAGNOSIS TREATMENTS PREVENTION LIVING WITH CLINICAL TRIALS LINKS Related ... with having iron-deficiency anemia. Prior to her diagnosis, Susan had symptoms such as tiredness, poor skin ...

  6. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... iron-rich protein that carries oxygen from the lungs to the rest of the body. Iron-deficiency ... 2011 This video—presented by the National Heart, Lung, and Blood Institute, part of the National Institutes ...

  7. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... can cause fatigue (tiredness), shortness of breath, chest pain, and other symptoms. Severe iron-deficiency anemia can ... colon cancer Regular use of aspirin or other pain medicines, such as nonsteroidal anti-inflammatory drugs (for ...

  8. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... or an inability to absorb enough iron from food. Overview Iron-deficiency anemia is a common type ... or an inability to absorb enough iron from food. Blood Loss When you lose blood, you lose ...

  9. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... Infants and Young Children A baby's diet can affect his or her risk for iron-deficiency anemia. ... eat grapefruit or drink grapefruit juice. Grapefruit can affect the strength of a few medicines and how ...

  10. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... carry oxygen and remove carbon dioxide (a waste product) from your body. Anemia also can occur if ... Deficiency Anemia article. Updated: March 26, 2014 Twitter Facebook YouTube Google+ SITE INDEX ACCESSIBILITY PRIVACY STATEMENT FOIA ...

  11. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... drawings also can cause iron-deficiency anemia. Poor Diet The best sources of iron are meat, poultry, ... also checks the number of red blood cells, white blood cells, and platelets in your blood. Abnormal ...

  12. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... also can cause internal bleeding. Other At-Risk Groups People who get kidney dialysis treatment may develop ... and young children and women are the two groups at highest risk for iron-deficiency anemia. Special ...

  13. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... the signs and symptoms of iron-deficiency anemia apply to all types of anemia . Signs and Symptoms ... rapid or uneven breathing Feel your abdomen to check the size of your liver and spleen Do ...

  14. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... iron-deficiency anemia may require treatment in a hospital, blood transfusions , iron injections, or intravenous iron therapy. ... beans. Other lifestyle changes, such as getting enough sleep and exercising, also have helped Susan feel better. ...

  15. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... intestine (such as Crohn's disease or celiac disease). Prescription medicines that reduce acid in the stomach also ... specialists also may help treat iron-deficiency anemia. Medical History Your doctor will ask about your signs ...

  16. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... specialists also may help treat iron-deficiency anemia. Medical History Your doctor will ask about your signs ... information, go to the Health Topics Blood Transfusion article. Iron Therapy If you have severe anemia, your ...

  17. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... drawings also can cause iron-deficiency anemia. Poor Diet The best sources of iron are meat, poultry, ... other dark green leafy vegetables Prune juice The Nutrition Facts labels on packaged foods will show how ...

  18. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... Other At-Risk Groups People who get kidney dialysis treatment may develop iron-deficiency anemia. This is because blood is lost during dialysis. Also, the kidneys are no longer able to ...

  19. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... for iron-deficiency anemia The Centers for Disease Control and Prevention (CDC) has developed guidelines for who ... heavy menstrual flow, your doctor may prescribe birth control pills to help reduce your monthly blood flow. ...

  20. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... screened for iron deficiency, and how often: Girls aged 12 to 18 and women of childbearing age ... For this treatment, iron is injected into a muscle or an IV line in one of your ...

  1. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... factors for iron-deficiency anemia The Centers for Disease Control and Prevention (CDC) has developed guidelines for who should be ... or while checking for other problems. Specialists ... disease specialist), a gastroenterologist (a digestive system specialist), and ...

  2. Iron deficiency anemia

    National Research Council Canada - National Science Library

    Naigamwalla, Dinaz Z; Webb, Jinelle A; Giger, Urs

    2012-01-01

    .... The most important function is oxygen transport in hemoglobin. Iron deficiency anemia in dogs and cats is usually caused by chronic blood loss and can be discovered incidentally as animals may have adapted to the anemia...

  3. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... stomach also can interfere with iron absorption. Risk Factors Infants and Young Children Infants and young children ... blood loss during their monthly periods Other risk factors for iron-deficiency anemia The Centers for Disease ...

  4. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... some stages of life, such as pregnancy and childhood, it may be hard to get enough iron ... supports concerns that iron deficiency during infancy and childhood can have long-lasting, negative effects on brain ...

  5. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... For this treatment, iron is injected into a muscle or an IV line in one of your ... body can damage your organs. You may have fatigue (tiredness) and other symptoms of iron-deficiency anemia ...

  6. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... risk for iron-deficiency anemia if they're underweight or have chronic (ongoing) illnesses. Teenage girls who ... other dark green leafy vegetables Prune juice The Nutrition Facts labels on packaged foods will show how ...

  7. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... deficiency anemia if they're underweight or have chronic (ongoing) illnesses. Teenage girls who have heavy periods ... in your hands and feet, pale skin, chest pain, weakness, and fatigue (tiredness). If you don't ...

  8. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... intravenous iron therapy. Rate This Content: NEXT >> Featured Video Living With and Managing Iron-Deficiency Anemia 05/18/2011 This video—presented by the National Heart, Lung, and Blood ...

  9. Sleep Deprivation and Deficiency

    Science.gov (United States)

    ... adults report falling asleep during the day without meaning to at least once a month. Also, an ... Sleep deficiency also has been linked to depression, suicide, and risk-taking behavior. Children and teens who ...

  10. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... prevent children's bodies from absorbing iron from other foods. Children who have lead in their blood also may be at risk for iron-deficiency anemia. Lead can interfere with ...

  11. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... Diseases Heart and Vascular Diseases Precision Medicine Activities Obesity, Nutrition, and Physical Activity Population and Epidemiology Studies ... or an inability to absorb enough iron from food. Overview Iron-deficiency anemia is a common type ...

  12. 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

  13. Glucose-6-phosphatase deficiency.

    OpenAIRE

    Labrune Philippe; Gajdos Vincent; Eberschweiler Pascale; Hubert-Buron Aurélie; Petit François; Vianey-Saban Christine; Boudjemline Alix; Piraud Monique; Froissart Roseline

    2011-01-01

    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, betw...

  14. MAGNESIUM DEFICIENCY IN CHILD NEUROLOGY: WHAT SHOULD A PAEDIATRICIAN KNOW?

    Directory of Open Access Journals (Sweden)

    G. А. Karkashadze

    2014-01-01

    Full Text Available Deficiency of micronutrients in a diet of the modern children increases risk of the formation of chronic neurologic and somatic pathology. Magnesium deficiency, which initiates a various neurologic symptomatology, has a particular importance in the progress of nervous system diseases at children. Diagnosis of neurologic manifestations of a micronutrient deficiency requires comprehension of the main mechanisms of their development, and also peculiarities of laboratory diagnostics. In treatment of consequences of a magnesium deficiency the special role belongs to the micronutrient stock replacement (medication, alimentary combined with traditional methods of treatment of neurologic disorders.

  15. [Treatable Dementia due to Vitamin B12 and Folate Deficiency].

    Science.gov (United States)

    Yoshizawa, Toshihiro

    2016-04-01

    Vitamin deficiency is one of the major causes of treatable dementia. Specifically, patients suffering from dementia frequentry display low serum levels of vitamin B(12). There is a close metabolic interaction between folate and vitamin B(12). Folate deficiency causes various neuropsychiatric symptoms, which resemble those observed in vitamin B(12) deficiency. This review summarizes, the basic pathophysiology of vitamin B(12) and folate deficiency, its clinical diagnosis, associated neuropsychiatric symptoms such as subacute combined degeneration and dementia, and epidemiological studies of cognitive decline and brain atrophy.

  16. Long-term skeletal effects of recombinant human growth hormone (rhGH) alone and rhGH combined with alendronate in GH-deficient adults: a seven-year follow-up study.

    Science.gov (United States)

    Biermasz, Nienke R; Hamdy, Neveen A T; Pereira, Alberto M; Romijn, Johannes A; Roelfsema, Ferdinand

    2004-05-01

    GH-deficient patients respond to recombinant human GH (rhGH) replacement therapy by increasing bone mineral density (BMD) at a rate of about 1% a year for at least 4 years. Predictive factors for a beneficial effect on bone are a low bone mass at baseline and gender. Whether the beneficial skeletal effects of GH are sustained in the long term remains to be established. It is also not known whether osteoporotic GH-deficient patients may require additional antiresorptive drugs and whether this treatment would be effective concomitantly with GH replacement. We performed a long-term, controlled study in 30 GH-deficient adults: 15 with osteoporosis and 15 control subjects with low bone mass. All patients were treated with rhGH for at least 4 years; thereafter, 3 years of additional alendronate treatment was given to patients with osteoporosis, while controls continued on GH therapy alone. The GH dose was individualized to maintain an IGF-I within the normal reference range for the duration of the study, and was equal between genders. At the end of 4 years of rhGH replacement therapy, a significant increase in mean lumbar spine BMD was observed in both the osteoporosis group (3.6%) and the control group (7.0%), with no significant difference between groups. Males had a larger increase in BMD than females (P = 0.032). After 4 or 5 years of GH treatment patients with persisting osteoporosis received additional alendronate (10 mg/day) for 3 years. Lumbar spine BMD increased by 8.7% after 3 years (P = 0.001) vs 1.5% (P = NS) in the control group continuing on rhGH replacement alone. The alendronate effect was gender independent (P = 0.59). Mean bone area of the lumbar spine did not change in both groups for the duration of the study. Femoral neck BMD increased significantly in the osteoporosis group (3.5%) and was unchanged in the control group. Five osteoporotic GH-deficient patients had a total of 12 vertebral fractures before start of alendronate. Only one of these

  17. Iron deficiency in Europe.

    Science.gov (United States)

    Hercberg, S; Preziosi, P; Galan, P

    2001-04-01

    In Europe, iron deficiency is considered to be one of the main nutritional deficiency disorders affecting large fractions of the population, particularly such physiological groups as children, menstruating women and pregnant women. Some factors such as type of contraception in women, blood donation or minor pathological blood loss (haemorrhoids, gynaecological bleeding...) considerably increase the difficulty of covering iron needs. Moreover, women, especially adolescents consuming low-energy diets, vegetarians and vegans are at high risk of iron deficiency. Although there is no evidence that an absence of iron stores has any adverse consequences, it does indicate that iron nutrition is borderline, since any further reduction in body iron is associated with a decrease in the level of functional compounds such as haemoglobin. The prevalence of iron-deficient anaemia has slightly decreased in infants and menstruating women. Some positive factors may have contributed to reducing the prevalence of iron-deficiency anaemia in some groups of population: the use of iron-fortified formulas and iron-fortified cereals; the use of oral contraceptives and increased enrichment of iron in several countries; and the use of iron supplements during pregnancy in some European countries. It is possible to prevent and control iron deficiency by counseling individuals and families about sound iron nutrition during infancy and beyond, and about iron supplementation during pregnancy, by screening persons on the basis of their risk for iron deficiency, and by treating and following up persons with presumptive iron deficiency. This may help to reduce manifestations of iron deficiency and thus improve public health. Evidence linking iron status with risk of cardiovascular disease or cancer is unconvincing and does not justify changes in food fortification or medical practice, particularly because the benefits of assuring adequate iron intake during growth and development are well established

  18. [Effects of copper deficiency on iron metabolism in rats].

    Science.gov (United States)

    Xiao, Fei; Wang, Chaoxu; Yang, Li

    2013-07-01

    To study the effects of copper deficiency on iron metabolism, the expression of IRP mRNA and Fn mRNA and transferrin receptor mRNA in rats. Forty clean male SD rats were randomly divided into four groups according to body weight and there were 10 rats in each group. The groups are normal iron and copper control group (group I), copper deficiency group (group II), normal iron and copper slightly deficient group (group III), both iron and copper slightly deficient group (group IV). After 8 weeks, all the rats were killed by sodium pentobarbital anesthesia and all samples were collected and detected for gene expression. Compared with the controls, the contents of serum iron and serum ferritin in completely copper deficiency group decreased (P copper deficiency (P copper deficiency group was significantly increased (P copper deficiency group was significantly decreased (P copper deficiency through influencing the absorption, the results indicate that copper deficiency influences iron homeostasis in cells through affecting the expression of IRP2 and the activity of IRP-RNA combination which change the expressions of ferritin and transferrin mRNA.

  19. Comparação do treinamento físico de quatro e oito semanas sobre atividade da cadeia transportadora de elétrons e marcadores de estresse oxidativo em fígado de camundongos Comparison between four- and eight- week physical trainings on the mitochondrial respiratory chain enzyme activities and oxidative stress markers in liver of mice

    Directory of Open Access Journals (Sweden)

    Luciano A. Silva

    2010-04-01

    content in liver when compared to untrained animals. Decrease in protein carbonylation in the respective group in relation to UT was also observed. It could be concluded that eight weeks of running training are necessary for mitochondrial respiratory chain enzyme activities increase and improvement in oxidative stress markers in liver of mice.

  20. Deficiências de minerais Mineral deficiencies

    Directory of Open Access Journals (Sweden)

    Silvia Maria Franciscato Cozzolino

    2007-08-01

    Full Text Available Neste artigo procuramos relatar a situação mundial e brasileira com relação aos micronutrientes, em especial sobre os minerais. Os elementos químicos minerais desempenham funções de grande importância no organismo humano, sendo indispensáveis para o desenvolvimento e a saúde dos indivíduos. Ainda não existe uma avaliação global do estado nutricional dos indivíduos em relação a esses micronutrientes no Brasil, mas os estudos existentes apontam para a necessidade do acompanhamento das tendências alimentares que poderiam levar às suas deficiências com conseqüências adversas para a saúde da população e o desenvolvimento do nosso país.In this paper we will try to report the Brazilian micronutrients status, as well as in worldwide, specifically for minerals. Minerals have major importance on human body, becoming indispensable for the development and health of individuals. There is not yet an integral assessment of micronutrient status in the Brazilian subjects, but there are some studies pointing to the need of observation of alimentary tendencies that might lead to deficiencies, with adverse consequences to the population’s health and the development of our country

  1. Deficiency of the iron-sulfur clusters of mitochondrial reduced nicotinamide-adenine dinucleotide-ubiquinone oxidoreductase (complex I) in an infant with congenital lactic acidosis.

    Science.gov (United States)

    Moreadith, R W; Batshaw, M L; Ohnishi, T; Kerr, D; Knox, B; Jackson, D; Hruban, R; Olson, J; Reynafarje, B; Lehninger, A L

    1984-01-01

    We report the case of an infant with hypoglycemia, progressive lactic acidosis, an increased serum lactate/pyruvate ratio, and elevated plasma alanine, who had a moderate to profound decrease in the ability of mitochondria from four organs to oxidize pyruvate, malate plus glutamate, citrate, and other NAD+-linked respiratory substrates. The capacity to oxidize the flavin adenine dinucleotide-linked substrate, succinate, was normal. The most pronounced deficiency was in skeletal muscle, the least in kidney mitochondria. Enzymatic assays on isolated mitochondria ruled out defects in complexes II, III, and IV of the respiratory chain. Further studies showed that the defect was localized in the inner membrane mitochondrial NADH-ubiquinone oxidoreductase (complex I). When ferricyanide was used as an artificial electron acceptor, complex I activity was normal, indicating that electrons from NADH could reduce the flavin mononucleotide cofactor. However, electron paramagnetic resonance spectroscopy performed on liver submitochondrial particles showed an almost total loss of the iron-sulfur clusters characteristic of complex I, whereas normal signals were noted for other mitochondrial iron-sulfur clusters. This infant is presented as the first reported case of congenital lactic acidosis caused by a deficiency of the iron-sulfur clusters of complex I of the mitochondrial electron transport chain. Images PMID:6432847

  2. Screening for active small molecules in mitochondrial complex I deficient patient's fibroblasts, reveals AICAR as the most beneficial compound.

    Directory of Open Access Journals (Sweden)

    Anna Golubitzky

    Full Text Available Congenital deficiency of the mitochondrial respiratory chain complex I (CI is a common defect of oxidative phosphorylation (OXPHOS. Despite major advances in the biochemical and molecular diagnostics and the deciphering of CI structure, function assembly and pathomechanism, there is currently no satisfactory cure for patients with mitochondrial complex I defects. Small molecules provide one feasible therapeutic option, however their use has not been systematically evaluated using a standardized experimental system. In order to evaluate potentially therapeutic compounds, we set up a relatively simple system measuring different parameters using only a small amount of patient's fibroblasts, in glucose free medium, where growth is highly OXPOS dependent. Ten different compounds were screened using fibroblasts derived from seven CI patients, harboring different mutations.5-Aminoimidazole-4-carboxamide ribotide (AICAR was found to be the most beneficial compound improving growth and ATP content while decreasing ROS production. AICAR also increased mitochondrial biogenesis without altering mitochondrial membrane potential (Δψ. Fluorescence microscopy data supported increased mitochondrial biogenesis and activation of the AMP activated protein kinase (AMPK. Other compounds such as; bezafibrate and oltipraz were rated as favorable while polyphenolic phytochemicals (resverastrol, grape seed extract, genistein and epigallocatechin gallate were found not significant or detrimental. Although the results have to be verified by more thorough investigation of additional OXPHOS parameters, preliminary rapid screening of potential therapeutic compounds in individual patient's fibroblasts could direct and advance personalized medical treatment.

  3. Vitamin deficiencies in cattle.

    Science.gov (United States)

    Frye, T M; Williams, S N; Graham, T W

    1991-03-01

    Deficiencies of vitamins A, D, K, E and thiamin can cause severe limitations in beef production. In particular, vitamin A and E can be common causes of lost profit, secondary to limitations of reproductive and growth potential. Prolonged dry periods will reduce available A and E in pasture forage, as can ensiling and prolonged storage of harvested feedstuffs. Polioencephalomalacia is a thiamin responsive disorder, associated with high concentrate feeding and lush pastures. Antimetabolites, such as amprolium, will cause thiamine deficiency when fed in excess. Recent information has shown improved performance with supplemental beta carotene and niacin. The positive responses in reproductive performance, noted with cattle fed supplemental beta carotene, was independent of vitamin A. Supplementation of vitamins above National Research Council recommendations can be justified. However, proper evaluation of feed and animal status, and documentation of a response to supplementation is necessary before diagnosing deficiencies of specific nutrients.

  4. Vitamin B12 deficiency

    DEFF Research Database (Denmark)

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

    2017-01-01

    Vitamin B12 (B12; also known as cobalamin) is a B vitamin that has an important role in cellular metabolism, especially in DNA synthesis, methylation and mitochondrial metabolism. Clinical B12 deficiency with classic haematological and neurological manifestations is relatively uncommon. However...... remain debated. Management depends on B12 supplementation, either via high-dose oral routes or via parenteral administration. This Primer describes the current knowledge surrounding B12 deficiency, and highlights improvements in diagnostic methods as well as shifting concepts about the prevalence, causes...

  5. Multiple sulfatase deficiency.

    Science.gov (United States)

    Soong, B W; Casamassima, A C; Fink, J K; Constantopoulos, G; Horwitz, A L

    1988-08-01

    Multiple sulfatase deficiency is an inherited disorder characterized by a deficiency of several sulfatases and the accumulation of sulfatides, glycosaminoglycans, sphingolipids, and steroid sulfates in tissues and body fluids. The clinical manifestations represent the summation of two diseases: late infantile metachromatic leukodystrophy and mucopolysaccharidosis. We present a 9-year-old girl with a phenotype similar to a mucopolysaccharidosis: short stature, microcephaly, and mild facial dysmorphism, along with dysphagia, retinal degeneration, developmental arrest, and ataxia. We discuss the importance of measuring the sulfatase activities in the leukocytes, and the instability of sulfatases in the cultured skin fibroblasts.

  6. Iodine Deficiency and Human Development

    Directory of Open Access Journals (Sweden)

    M A Sviridonova

    2014-03-01

    Full Text Available Iodine is а vital microelements that are essential for the normal human development and functions. Iodine deficiency is a global problem: about 2 billion individuals worldwide suffer from a lack of iodine. Despite goiter is the most visually noticeable manifestation of iodine deficiency, the most significant consequence of the iodine deficiency is impaired neurodevelopment, particularly early in life. Moreover, moderate to severe iodine deficiency increases the risk of spontaneous abortion, low birth weight and infant mortality. Babies in utero affected by iodine deficiency are at increased risk of mental developmental disorders, cretinism is their extreme degree. In addition, moderate to severe iodine deficiency in childhood negatively affects somatic growth. Iodine deficiency compensation improves cognitive and motor function in children. Iodine prophylaxis of deficient populations is an extremely effective approach to reduce the substantial adverse effects of iodine deficiency throughout the life cycle.

  7. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... your red blood cells don't contain enough hemoglobin (HEE-muh-glow-bin). Hemoglobin is an iron-rich protein that carries oxygen ... red blood cells it does make have less hemoglobin than normal. Iron-deficiency anemia can cause fatigue ( ...

  8. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... Every 5 to 10 years. Women who have risk factors for iron deficiency: Once a year. Pregnant women: At the first prenatal visit. For pregnant women, medical care during pregnancy usually includes screening for anemia. Also, your doctor ...

  9. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... Severe iron-deficiency anemia can lead to heart problems, infections, problems with growth and development in children, and other ... poorly because of money, social, health, or other problems. Follow a very low-fat diet over a ...

  10. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... deficiency anemia if they're underweight or have chronic (ongoing) illnesses. Teenage girls who have heavy periods ... because blood is lost during dialysis. Also, the kidneys are no longer able to make ... Centers for Disease Control and Prevention (CDC) has developed guidelines for ...

  11. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... iron-rich foods in the diet. Too much milk also may prevent children's bodies from absorbing iron from other foods. Children who have lead in their blood also may be at risk for iron-deficiency anemia. Lead can interfere with the body's ability to make hemoglobin. Lead may get into the body from ...

  12. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... also may help treat iron-deficiency anemia. Medical History Your doctor will ask about your signs and symptoms and any past problems you've had with anemia or low iron. He or she also may ask about your diet and whether you're taking any medicines. If ...

  13. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... Site Health Topics News & Resources Intramural Research ... Is Iron-deficiency anemia is a common, easily treated condition that occurs if you don't have enough iron in your body. Low iron levels usually are due to blood loss, ...

  14. Deficiency Report Management System

    Science.gov (United States)

    1989-09-28

    The Customer Feedback Office of the Product Assurance Directorate, MICOM has the mission to manage and analyze data in the Deficiency Reporting...capability within the Customer Feedback Office (CFO) of the MICOM Product Assurance Directorate for government comment. The objective of this program is

  15. Partial Biotinidase Deficiency

    OpenAIRE

    J Gordon Millichap

    1990-01-01

    The symptoms, biochemical features and inheritance pattern of partial biotinidase deficiency have been studied at the Departments of Human Genetics and Pediatrics, Medical College of Virginia, Richmond, VA; the State Laboratory Institute, Massachusetts Department of Public Health; Massachusetts General Hospital, Boston; the Lincoln Clinic, NB; and the Division of Human Genetics, university of Maryland School of Medicine, Baltimore.

  16. Iodine-deficiency disorders

    NARCIS (Netherlands)

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

    2008-01-01

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

  17. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... Activity Population and Epidemiology Studies Women’s Health All Science A-Z ... usually are due to blood loss, poor diet, or an inability to absorb enough iron from food. Overview Iron-deficiency anemia is a common type ...

  18. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... doctor may ask whether you might be pregnant. Physical Exam Your doctor will do a physical exam to look for signs of iron-deficiency ... remove the growth. If you have heavy menstrual flow, your doctor may prescribe birth control pills to ...

  19. Alpha-1 antitrypsin deficiency

    Science.gov (United States)

    ... Tools About MedlinePlus Show Search Search MedlinePlus GO GO About MedlinePlus Site Map FAQs Customer Support Health Topics Drugs & Supplements Videos & Tools Español You Are Here: Home → Medical Encyclopedia → Alpha-1 antitrypsin deficiency URL of this page: //medlineplus. ...

  20. Vitamin B12 deficiency

    Science.gov (United States)

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

  1. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... hospital, blood transfusions , iron injections, or intravenous iron therapy. Causes Not having enough iron in your body causes iron-deficiency anemia. Lack of iron usually is due to blood loss, poor diet, or an inability to absorb enough iron from ...

  2. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... blood transfusions , iron injections, or intravenous iron therapy. Rate This Content: NEXT >> Featured Video Living With and Managing Iron-Deficiency Anemia 05/18/2011 This video—presented by the National Heart, Lung, and Blood Institute, part of the National ...

  3. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... who have iron-deficiency anemia develop restless legs syndrome (RLS). RLS is a disorder that causes a ... Topics Anemia Blood Tests Blood Transfusion Restless Legs Syndrome Other Resources Non-NHLBI Resources Anemia (MedlinePlus) "Dietary ...

  4. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... the body. Iron-deficiency anemia usually develops over time if your body doesn't have enough iron ... Institutes of Health—shows how Susan, a full-time worker and student, has coped with having iron- ...

  5. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... woman's risk for a premature or low-birth-weight baby. Adults Who Have Internal Bleeding Adults who have internal bleeding, such as intestinal bleeding, can develop iron-deficiency anemia due to blood loss. Certain conditions, such as colon cancer and bleeding ...

  6. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... as larger, full-term infants. Iron-fortified baby food or iron supplements, when used properly, can help prevent iron-deficiency ... Syndrome Other Resources Non-NHLBI Resources Anemia (MedlinePlus) "Dietary Supplement Fact Sheet: Iron" (Office of Dietary Supplements, National ...

  7. Chronic glomerulonephritis associated with IgG subclass deficiency.

    Science.gov (United States)

    Kamei, Koichi; Nakagawa, Atsuko; Otsuka, Yasufumi; Nakayama, Makiko; Kobayashi, Shinichi; Matsuoka, Kentaro; Iijima, Kazumoto

    2007-08-01

    We experienced two patients with IgG subclass deficiency who suffered from chronic glomerulonephritis (GN). Patient 1 was a 17-year-old girl with IgG subclass deficiency (combined deficiency of IgG2 and IgG4). Renal biopsy was performed when she was aged 16 years, and she was diagnosed with membranoproliferative GN. Patient 2 was a 16-year-old girl with IgG subclass deficiency (combined deficiency of IgG2, IgG3, and IgG4). Renal biopsy was performed when she was aged 15 years, and she was diagnosed with membranous nephropathy. We examined the glomerular deposition patterns of their IgG subclasses. Furthermore, we compared their clinical and laboratory findings with those of three patients with IgG subclass deficiency without GN. Patients with GN suffered infections more frequently than those without GN. The serum levels of IgG (especially IgG1) and IgM were higher in patients with GN than in those without GN. In patient 1 IgG1 and IgG3 were deposited in a mesangiocapillary pattern, but, in patient 2, only IgG1 was deposited in a capillary pattern. Thus, the different patterns of IgG subclass deficiency between the two patients may be responsible for their different glomerular pathologies. To the best of our knowledge, this is the first report of chronic GN in patients with IgG subclass deficiency.

  8. Immunoglobulin G (IgG) subclass deficiency in Thai children.

    Science.gov (United States)

    Visitsunthorn, Nualanong; Hengcrawit, Wiriya; Jirapongsananuruk, Orathai; Luangwedchakam, Voravich

    2011-12-01

    Patients with Immunoglobulin G (IgG) subclass deficiency may suffer from recurrent infections, mainly sino-pulmonary infection. To determine the epidemiology of IgG subclass deficiency in Thai children at a tertiary care hospital and to compare the differences between children who were diagnosed with IgG subclass deficiency by using low level criteria [less than 2 standard deviation (SD) of normal levels for age] and by using low percentage criteria (proportion of each IgG subclasses/total IgG). The study was a descriptive study of 55 children up to 15 years old with recurrent infections diagnosed as having IgG subclass deficiency but no acquired or other primary immune deficiencies except for IgA and/or IgM deficiency. Isolated IgG3 subclass deficiency was the most common IgG subclass deficiency (56.4%). IgG3 subclass deficiency, either isolated or combined with other IgG subclass deficiency, was found in 85.5% of the cases. The common age of onset was between birth and five years of age. The most common presenting symptom was recurrent sinusitis (83.6%). Majority of the cases (89.3%) were diagnosed by low percentage criteria while 12.7% were diagnosed by low level criteria. All cases with low levels of IgG subclass antibodies also had low percentages. There were no statistically significant differences in the clinical manifestations and management methods between the children who were diagnosed by low level and low percentage. IgG3 subclass deficiency was the most common IgG subclass deficiency in Thai children. The most common presenting symptom was recurrent sinusitis. Although the diagnosis could be made in the patients with recurrent upper respiratory infection by using low level criteria, but the diagnosis should be considered when the low percentage criteria are met.

  9. Glucose-6-phosphate dehydrogenase deficiency

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/000528.htm Glucose-6-phosphate dehydrogenase deficiency To use the sharing features on this page, please enable JavaScript. Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a condition ...

  10. Genetics Home Reference: transcobalamin deficiency

    Science.gov (United States)

    ... PH, Nordwall M, Hoffmann-Lücke E, Sorensen BS, Nexo E. Transcobalamin deficiency caused by compound heterozygosity for ... Hung C, Rupar T, Mühl A, Fowler B, Nexo E, Bodamer OA. Transcobalamin II deficiency at birth. ...

  11. Genetics Home Reference: proopiomelanocortin deficiency

    Science.gov (United States)

    ... due to pomc deficiency Orphanet: Obesity due to pro-opiomelanocortin deficiency Patient Support and Advocacy Resources (4 ... HH, Wallace SE, Amemiya A, Bean LJH, Bird TD, Ledbetter N, Mefford HC, Smith RJH, Stephens K, ...

  12. Growth Hormone Deficiency in Children

    Science.gov (United States)

    ... c m y one in Children What is growth hormone deficiency? Growth hormone deficiency (GHD) is a rare condition in which the body does not make enough growth hormone (GH). GH is made by the pituitary gland, ...

  13. Growth Hormone Deficiency in Adults

    Science.gov (United States)

    ... Balance › Growth Hormone Deficiency in Adults Patient Guide Growth Hormone Deficiency in Adults June 2011 Download PDFs English ... depression, or moodiness What are the benefits of growth hormone therapy? Growth hormone treatment involves injections (shots) of ...

  14. Adult growth hormone deficiency treatment with a combination of growth hormone and insulin-like growth factor-1 resulting in elevated sustainable insulin-like growth factor-1 and insulin-like growth factor binding protein 3 plasma levels: a case report

    Directory of Open Access Journals (Sweden)

    Madigan Margaret

    2010-09-01

    Full Text Available Abstract Introduction Adult Growth hormone Deficiency is a well known phenomenon effecting both males and females. Adult Growth Hormone Deficiency is marked by a number of neuropsychiatric, cognitive performance, cardiac, metabolic, muscular, and bone symptoms and clinical features. There is no known standardized acceptable therapeutic modality to treat this condition. A recent meta-analysis found that after 16 years of Growth Hormone replacement therapy a large proportion of the patients still had Growth Hormone associated symptoms especially related to executive functioning. A major goal is to increase plasma levels of both insulin-like growth factor (insulin-like growth factor-1 and insulin-like growth factor binding protein 3. Case Presentation We report a case of a 45-year-old caucasian woman with early ovarian failure for 2 years and amenorrhea since the age of 43, who presented with Adult Growth Hormone Deficiency and an IGF-1 of 126 ng/mL. Since her insulin-like growth factor-1 was lowest at 81 ng/mL, she was started on insulin-like growth factor-1 Increlex at 0.2 mg at bedtime, which immediately raised her insulin-like growth factor-1 levels to 130 ng/mL within 1 month, and 193 ng/mL, 249 ng/mL, and 357 ng/mL, after 3, 4, and 5 months, respectively, thereafter. Her insulin-like growth factor binding protein 3 continued to decrease. It was at this point when we added back the Growth Hormone and increased her Increlex dosage to 1.3 - 1.5 mg that her insulin-like growth factor binding protein 3 began to increase. Conclusion It appears that in some patients with Adult Growth Hormone Deficiency, insulin-like growth factor-1 elevation is resistant to direct Growth Hormone treatment. Furthermore, the binding protein may not rise with insulin-like growth factor-1. However, a combination of Growth Hormone and insulin-like growth factor-1 treatment may be a solution.

  15. NAD(PH: quinone oxidoreductase 1 deficiency conjoint with marginal vitamin C deficiency causes cigarette smoke induced myelodysplastic syndromes.

    Directory of Open Access Journals (Sweden)

    Archita Das

    Full Text Available BACKGROUND: The etiology of myelodysplastic syndromes (MDS is largely unknown. Exposure to cigarette smoke (CS is reported to be associated with MDS risk. There is inconsistent evidence that deficiency of NAD(PH-quinone: oxidoreductase 1 (NQO1 increases the risk of MDS. Earlier we had shown that CS induces toxicity only in marginal vitamin C-deficient guinea pigs but not in vitamin C-sufficient ones. We therefore considered that NQO1 deficiency along with marginal vitamin C deficiency might produce MDS in CS-exposed guinea pigs. METHODOLOGY AND PRINCIPAL FINDINGS: Here we show that CS exposure for 21 days produces MDS in guinea pigs having deficiency of NQO1 (fed 3 mg dicoumarol/day conjoint with marginal vitamin C deficiency (fed 0.5 mg vitamin C/day. As evidenced by morphology, histology and cytogenetics, MDS produced in the guinea pigs falls in the category of refractory cytopenia with unilineage dysplasia (RCUD: refractory anemia; refractory thrombocytopenia that is associated with ring sideroblasts, micromegakaryocytes, myeloid hyperplasia and aneuploidy. MDS is accompanied by increased CD34(+ cells and oxidative stress as shown by the formation of protein carbonyls and 8-oxodeoxyguanosine. Apoptosis precedes MDS but disappears later with marked decrease in the p53 protein. MDS produced in the guinea pigs are irreversible. MDS and all the aforesaid pathophysiological events do not occur in vitamin C-sufficient guinea pigs. However, after the onset of MDS vitamin C becomes ineffective. CONCLUSIONS AND SIGNIFICANCE: CS exposure causes MDS in guinea pigs having deficiency of NQO1 conjoint with marginal vitamin C deficiency. The syndromes are not produced in singular deficiency of NQO1 or marginal vitamin C deficiency. Our results suggest that human smokers having NQO1 deficiency combined with marginal vitamin C deficiency are likely to be at high risk for developing MDS and that intake of a moderately large dose of vitamin C would prevent MDS.

  16. 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

  17. A SLC39A8 variant causes manganese deficiency, and glycosylation and mitochondrial disorders.

    Science.gov (United States)

    Riley, Lisa G; Cowley, Mark J; Gayevskiy, Velimir; Roscioli, Tony; Thorburn, David R; Prelog, Kristina; Bahlo, Melanie; Sue, Carolyn M; Balasubramaniam, Shanti; Christodoulou, John

    2017-03-01

    SLC39A8 variants have recently been reported to cause a type II congenital disorder of glycosylation (CDG) in patients with intellectual disability and cerebellar atrophy. Here we report a novel SLC39A8 variant in siblings with features of Leigh-like mitochondrial disease. Two sisters born to consanguineous Lebanese parents had profound developmental delay, dystonia, seizures and failure to thrive. Brain MRI of both siblings identified bilateral basal ganglia hyperintensities on T2-weighted imaging and cerebral atrophy. CSF lactate was elevated in patient 1 and normal in patient 2. Respiratory chain enzymology was only performed on patient 1 and revealed complex IV and II + III activity was low in liver, with elevated complex I activity. Complex IV activity was borderline low in patient 1 muscle and pyruvate dehydrogenase activity was reduced. Whole genome sequencing identified a homozygous Chr4(GRCh37):g.103236869C>G; c.338G>C; p.(Cys113Ser) variant in SLC39A8, located in one of eight regions identified by homozygosity mapping. SLC39A8 encodes a manganese and zinc transporter which localises to the cell and mitochondrial membranes. Patient 2 blood and urine manganese levels were undetectably low. Transferrin electrophoresis of patient 2 serum revealed a type II CDG defect. Oral supplementation with galactose and uridine led to improvement of the transferrin isoform pattern within 14 days of treatment initiation. Oral manganese has only recently been added to the treatment. These results suggest SLC39A8 deficiency can cause both a type II CDG and Leigh-like syndrome, possibly via reduced activity of the manganese-dependent enzymes β-galactosyltransferase and mitochondrial manganese superoxide dismutase.

  18. Vitamin D deficiency in early pregnancy.

    Directory of Open Access Journals (Sweden)

    Shannon K Flood-Nichols

    Full Text Available Vitamin D deficiency is a common problem in reproductive-aged women in the United States. The effect of vitamin D deficiency in pregnancy is unknown, but has been associated with adverse pregnancy outcomes. The objective of this study was to analyze the relationship between vitamin D deficiency in the first trimester and subsequent clinical outcomes.This is a retrospective cohort study. Plasma was collected in the first trimester from 310 nulliparous women with singleton gestations without significant medical problems. Competitive enzymatic vitamin D assays were performed on banked plasma specimens and pregnancy outcomes were collected after delivery. Logistic regression was performed on patients stratified by plasma vitamin D concentration and the following combined clinical outcomes: preeclampsia, preterm delivery, intrauterine growth restriction, gestational diabetes, and spontaneous abortion.Vitamin D concentrations were obtained from 235 patients (mean age 24.3 years, range 18-40 years. Seventy percent of our study population was vitamin D insufficient with a serum concentration less than 30 ng/mL (mean serum concentration 27.6 ng/mL, range 13-71.6 ng/mL. Logistic regression was performed adjusting for age, race, body mass index, tobacco use, and time of year. Adverse pregnancy outcomes included preeclampsia, growth restriction, preterm delivery, gestational diabetes, and spontaneous abortion. There was no association between vitamin D deficiency and composite adverse pregnancy outcomes with an adjusted odds ratio of 1.01 (p value 0.738, 95% confidence intervals 0.961-1.057.Vitamin D deficiency did not associate with adverse pregnancy outcomes in this study population. However, the high percentage of affected individuals highlights the prevalence of vitamin D deficiency in young, reproductive-aged women.

  19. Biotin and biotinidase deficiency

    OpenAIRE

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

    2008-01-01

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

  20. Electrophoretic characterization of D. melanogaster strains deficient in endogenous anti-oxidants in combination with gamma radiation; Caracterizacion electroforetica de cepas de D. melanogaster deficientes en antioxidantes endogenos en combinacion con radiacion gamma

    Energy Technology Data Exchange (ETDEWEB)

    Gomar A, S.

    2012-07-01

    The free radicals derived of the oxygen and other reactive species are generated by endogenous processes as sub-products of the aerobic metabolism or by exogenous factors as the environmental pollution, the biological half life of these free radicals is of microseconds, but they have the capacity of reacting with any atom or molecule to its around causing oxidant stress and damage to molecules, cellular membranes and tissues. To counteract them, there is endogenous and exogenous anti-oxidants, the first ones are synthesized by the organism for maintaining the cellular homeostasis as the superoxide dismutase and catalase. There are recent evidences that indicate that the sodium cooper chlorophyllin (SCC) presents a dual effect reducing and/or increasing the induced genetic damage by different mutagenic agents. One hypothesis for this effect is that the SCC can act as oxidant per se or through some of their metabolites. Results more recent indicated that a similar of the SCC, the protoporphyrin-Ix, can produce genetic damage. In this work exogenous anti-oxidants were used, as the SCC, protoporphyrin-Ix or the bilirubin in the induction of endogenous anti-oxidants enzymes to evaluate the supposed oxidant activity of the SCC and/or their metabolites. Drosophila melanogaster strains deficient in superoxide dismutase, catalase and withered were used and a rustic strain Canton-S as control. In the three experiments were treated 60 males of 1 day of age, with SCC, protoporphyrin-Ix or bilirubin to one concentration of 69 m M during 12 days. Every 4 days 10 males were isolated to measure them the induction of superoxide dismutase and catalase. The results showed that the SCC, protoporphyrin-Ix and bilirubin considered like anti-oxidants, were able to increase the induction of the superoxide dismutase and catalase enzymes. This result maybe is because they are able to generate reactive species of oxygen, as the anion superoxide and the hydrogen peroxide. Among the three

  1. Diagnosis of iron deficiency anemia in children of Northeast Brazil.

    Science.gov (United States)

    Carvalho, Antonio Geraldo Cidrão; Lira, Pedro Israel Cabral de; Barros, Maria de Fátima Alcântara; Aléssio, Maria Luiza Martins; Lima, Marília de Carvalho; Carbonneau, Marie Annette; Berger, Jacques; Léger, Claude Louis

    2010-06-01

    To diagnose iron deficiency anemia in children. The study was conducted with a sample of 301 children aged six to 30 months attending public daycare centers in the city of Recife, Northeast Brazil, in 2004. The diagnoses of anemia were based on a combination of different hematological and biochemical parameters: hemoglobin, mean corpuscular volume, ferritin, C-reactive protein, transferrin saturation and transferrin receptor. The chi-square test and ANOVA were used in the statistical analysis. Of all children studied, 92.4% had anemia (Hb<110 g/L) and 28.9% had moderate/severe anemia (Hb<90 g/L). Lower levels of hemoglobin were found in children aged 6-17 months. Iron deficiency was found in 51.5% of children using ferritin (<12 microg/L) as parameter. Taking into consideration the combination of hemoglobin level, ferritin and transferrin receptor, 58.1% had anemia with iron deficiency, 34.2% had anemia without iron deficiency and 2.3% had iron deficiency without anemia. Mean ferritin concentration was significantly higher in children with high C-reactive protein when compared with those with normal levels (22.1 vs. 14.8 microg/L). The use of several biochemical and hematological parameters allowed to diagnosing iron deficiency anemia in two thirds of children, suggesting a need to identify other determinants of anemia without iron deficiency.

  2. Cobalamin Deficiency: Clinical Picture and Radiological Findings

    Directory of Open Access Journals (Sweden)

    Chiara Briani

    2013-11-01

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

  3. Effects of Soluble Corn Fiber Alone or in Synbiotic Combination withLactobacillus rhamnosusGG and the Pilus-Deficient Derivative GG-PB12 on Fecal Microbiota, Metabolism, and Markers of Immune Function: A Randomized, Double-Blind, Placebo-Controlled, Crossover Study in Healthy Elderly (Saimes Study).

    Science.gov (United States)

    Costabile, Adele; Bergillos-Meca, Triana; Rasinkangas, Pia; Korpela, Katri; de Vos, Willem M; Gibson, Glenn R

    2017-01-01

    The aging process leads to a potential decline in immune function and adversely affects the gut microbiota. To date, many in vitro and in vivo studies focused on the application of synbiotics (prebiotics combined with probiotics) as a promising dietary approach to affect gut microbiota composition and improved functioning of the immune system. However, studies using synbiotic preparations often have the limitation that it remains unclear whether any effect observed is a result of the prebiotic or probiotic or a synergistic effect of the combined supplement. We investigated the effects of a probiotic Lactobacillus rhamnosus GG and pilus-deficient L. rhamnosus GG-PB12 combined with Promitor™ Soluble Corn Fiber (SCF, a candidate prebiotic) on fecal microbiota, metabolism, immunity, and blood lipids in healthy elderly persons. A prospective, double-blind, placebo controlled, randomized, single-centered, crossover study in 40 healthy elderly subjects (aged 60-80 years) was carried out. Volunteers were randomized to consume either probiotic and prebiotic as synbiotic, prebiotic or placebo (maltodextrin) during 3 weeks. Three-week washout periods separated all the treatments. We assessed effects upon blood lipids, glucose, cytokines, natural killer (NK) cell activity, phenotype, and intestinal microbiota composition. SCF decreased IL-6, which was not observed with the synbiotics. Consumption of L. rhamnosus GG combined with SCF increased NK cell activity compared to baseline in females and the older group. In the fecal microbiota analyses, the strongest community shifts were due to L. rhamnosus GG combined with SCF and SCF treatments. L. rhamnosus GG combined with SCF and L. rhamnosus GG-PB12 combined with SCF significantly increased the genus Parabacteroides . L. rhamnosus GG combined with SCF and SCF increased concentrations of Ruminococcaceae Incertae Sedis . Oscillospira and Desulfovibrio slightly decreased in the L. rhamnosus GG combined with SCF group, whereas

  4. Effects of Soluble Corn Fiber Alone or in Synbiotic Combination with Lactobacillus rhamnosus GG and the Pilus-Deficient Derivative GG-PB12 on Fecal Microbiota, Metabolism, and Markers of Immune Function: A Randomized, Double-Blind, Placebo-Controlled, Crossover Study in Healthy Elderly (Saimes Study

    Directory of Open Access Journals (Sweden)

    Adele Costabile

    2017-12-01

    Full Text Available BackgroundThe aging process leads to a potential decline in immune function and adversely affects the gut microbiota. To date, many in vitro and in vivo studies focused on the application of synbiotics (prebiotics combined with probiotics as a promising dietary approach to affect gut microbiota composition and improved functioning of the immune system. However, studies using synbiotic preparations often have the limitation that it remains unclear whether any effect observed is a result of the prebiotic or probiotic or a synergistic effect of the combined supplement.ObjectivesWe investigated the effects of a probiotic Lactobacillus rhamnosus GG and pilus-deficient L. rhamnosus GG-PB12 combined with Promitor™ Soluble Corn Fiber (SCF, a candidate prebiotic on fecal microbiota, metabolism, immunity, and blood lipids in healthy elderly persons. A prospective, double-blind, placebo controlled, randomized, single-centered, crossover study in 40 healthy elderly subjects (aged 60–80 years was carried out. Volunteers were randomized to consume either probiotic and prebiotic as synbiotic, prebiotic or placebo (maltodextrin during 3 weeks. Three-week washout periods separated all the treatments. We assessed effects upon blood lipids, glucose, cytokines, natural killer (NK cell activity, phenotype, and intestinal microbiota composition. SCF decreased IL-6, which was not observed with the synbiotics.ResultsConsumption of L. rhamnosus GG combined with SCF increased NK cell activity compared to baseline in females and the older group. In the fecal microbiota analyses, the strongest community shifts were due to L. rhamnosus GG combined with SCF and SCF treatments. L. rhamnosus GG combined with SCF and L. rhamnosus GG-PB12 combined with SCF significantly increased the genus Parabacteroides. L. rhamnosus GG combined with SCF and SCF increased concentrations of Ruminococcaceae Incertae Sedis. Oscillospira and Desulfovibrio slightly decreased in the L

  5. Prevalence of Iron Deficiency and Iron Deficiency Anemia in High-School Girl Students of Yazd

    Directory of Open Access Journals (Sweden)

    M Noori Shadkam

    2009-07-01

    Full Text Available Introduction: It is generally assumed that 50% of the cases of anemia are due to iron deficiency. The most severe consequence of iron depletion is iron deficiency anemia (IDA, and it is still considered the most common nutrition deficiency worldwide. The main risk factors for IDA include: inadequate iron intake, impaired absorption or transport, physiologic losses associated with chronological or reproductive age, or acute or chronic blood loss, parasite infections such as hookworms, acute and chronic infections, including malaria, cancer, tuberculosis, HIV and other micronutrient deficiencies, including vitamins A and B12, folate, riboflavin, and copper deficiency. Methods: This work as a cross-sectional study was done in 2007-2008 in Yazd. Two hundred girls who participated in the study were selected randomly from eight girl high schools. Five ml venous blood was collected for determination of serum ferritin and cell blood count (CBC. Serum ferritin was determined by using ECLIA method and CBC by cell counter SYSMEX KX21N. Iron deficiency was defined as having serum ferritin values below 12 μ/l. Anemia was defined as having Hemoglobin levels below12 g/dl. Iron-deficiency anemia was considered to be the combination of both. Results: The3 mean ageyears and body mass index (kg/m2 were 15.19±0.7years and 21.5±4.2, respectively. Distribution in the 14, 15 and 16 years and more age groups were 13, 58.5 and 28.5 percent, respectively. Mean of Hemoglobin(g/dl, Hematocrit(%, MCV (fl, MCH (pg, MCHC (g/dl and ferritin(μ/l were 12.8±0.9, 38.9±3.0, 80.7±4.3, 26.6±1.8, 33.2±3.6 and 23±18.2, respectively. Of the total, 13.5% were anemic, 68% of which had Iron Deficiency Anemia (9.3% of the total. Iron deficiency was present in 34.7% of the population under study. Conclusion: According to world health organization criteria, anemia is a mild public health problem in this region, but iron deficiency is a significant problem and suitable measures for

  6. FAST CP: protocol of a randomised controlled trial of the efficacy of a 12-week combined Functional Anaerobic and Strength Training programme on muscle properties and mechanical gait deficiencies in adolescents and young adults with spastic-type cerebral palsy.

    Science.gov (United States)

    Gillett, Jarred G; Lichtwark, Glen A; Boyd, Roslyn N; Barber, Lee A

    2015-06-26

    Individuals with cerebral palsy (CP) have muscles that are smaller, weaker and more resistant to stretch compared to typically developing people. Progressive resistance training leads to increases in muscle size and strength. In CP, the benefits of resistance training alone may not transfer to improve other activities such as walking; however, the transfer of strength improvements to improved mobility may be enhanced by performing training that involves specific functional tasks or motor skills. This study aims to determine the efficacy of combined functional anaerobic and strength training in (1) influencing muscle strength, structure and function and (2) to determine if any changes in muscle strength and structure following training impact on walking ability and gross motor functional capacity and performance in the short (following 3 months of training) and medium terms (a further 3 months post-training). 40 adolescents and young adults with CP will be recruited to undertake a 12-week training programme. The training programme will consist of 3 × 75 min sessions per week, made up of 5 lower limb resistance exercises and 2-3 functional anaerobic exercises per session. The calf muscles will be specifically targeted, as they are the most commonly impacted muscles in CP and are a key muscle group involved in walking. If, as we believe, muscle properties change following combined strength and functional training, there may be long-term benefits of this type of training in slowing the deterioration of muscle function in people with spastic-type CP. Ethical approval has been obtained from the ethics committees at The University of Queensland (2014000066) and Children's Health Queensland (HREC/15/QRCH/30). The findings will be disseminated by publications in peer-reviewed journals, conferences and local research organisations' media. Australian and New Zealand Clinical Trials Registry (ACTRN12614001217695). Published by the BMJ Publishing Group Limited. For permission

  7. FAST CP: protocol of a randomised controlled trial of the efficacy of a 12-week combined Functional Anaerobic and Strength Training programme on muscle properties and mechanical gait deficiencies in adolescents and young adults with spastic-type cerebral palsy

    Science.gov (United States)

    Gillett, Jarred G; Lichtwark, Glen A; Boyd, Roslyn N; Barber, Lee A

    2015-01-01

    Introduction Individuals with cerebral palsy (CP) have muscles that are smaller, weaker and more resistant to stretch compared to typically developing people. Progressive resistance training leads to increases in muscle size and strength. In CP, the benefits of resistance training alone may not transfer to improve other activities such as walking; however, the transfer of strength improvements to improved mobility may be enhanced by performing training that involves specific functional tasks or motor skills. This study aims to determine the efficacy of combined functional anaerobic and strength training in (1) influencing muscle strength, structure and function and (2) to determine if any changes in muscle strength and structure following training impact on walking ability and gross motor functional capacity and performance in the short (following 3 months of training) and medium terms (a further 3 months post-training). Methods and analysis 40 adolescents and young adults with CP will be recruited to undertake a 12-week training programme. The training programme will consist of 3×75 min sessions per week, made up of 5 lower limb resistance exercises and 2–3 functional anaerobic exercises per session. The calf muscles will be specifically targeted, as they are the most commonly impacted muscles in CP and are a key muscle group involved in walking. If, as we believe, muscle properties change following combined strength and functional training, there may be long-term benefits of this type of training in slowing the deterioration of muscle function in people with spastic-type CP. Ethics and dissemination Ethical approval has been obtained from the ethics committees at The University of Queensland (2014000066) and Children's Health Queensland (HREC/15/QRCH/30). The findings will be disseminated by publications in peer-reviewed journals, conferences and local research organisations’ media. Trial registration number Australian and New Zealand Clinical Trials

  8. In HepG2 Cells, Coexisting Carnitine Deficiency Masks Important Indicators of Marginal Biotin Deficiency123

    Science.gov (United States)

    Bogusiewicz, Anna; Boysen, Gunnar; Mock, Donald M

    2015-01-01

    Background: 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. Objective: In this study we hypothesized that coexisting carnitine deficiency can prevent the increase in 3HIAc due to biotin deficiency. Methods: 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. Results: 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

  9. [Iron deficiency and digestive disorders].

    Science.gov (United States)

    Cozon, G J N

    2014-11-01

    Iron deficiency anemia still remains problematic worldwide. Iron deficiency without anemia is often undiagnosed. We reviewed, in this study, symptoms and syndromes associated with iron deficiency with or without anemia: fatigue, cognitive functions, restless legs syndrome, hair loss, and chronic heart failure. Iron is absorbed through the digestive tract. Hepcidin and ferroportin are the main proteins of iron regulation. Pathogenic micro-organisms or intestinal dysbiosis are suspected to influence iron absorption. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  10. Autophagy induction by tetrahydrobiopterin deficiency

    OpenAIRE

    Kwak, Sang Su; Suk, Jinkyu; Choi, Ji Hye; Yang, Seungkyung; Kim, Jin Woo; Sohn, Seonghyang; Chung, Jae Hoon; Hong, Yong Hee; Lee, Dong Hwan; Ahn, Jeong Keun; Min, Hyesun; Fu, Ya-Min; Meadows, Gary G.; Joe, Cheol O.

    2011-01-01

    Tetrahydrobiopterin (BH4) deficiency is a genetic disorder associated with a variety of metabolic syndromes such as phenylketonuria (PKU). In this article, the signaling pathway by which BH4 deficiency inactivates mTORC1 leading to the activation of the autophagic pathway was studied utilizing BH4-deficient Spr-/- mice generated by the knockout of the gene encoding sepiapterin reductase (SR) catalyzing BH4 synthesis. We found that mTORC1 signaling was inactivated and autophagic pathway was ac...

  11. Rare coagulation factor deficiencies: a countrywide screening data from India.

    Science.gov (United States)

    Shetty, S; Shelar, T; Mirgal, D; Nawadkar, V; Pinto, P; Shabhag, S; Mukaddam, A; Kulkarni, B; Ghosh, K

    2014-07-01

    As compared to haemophilia, although the clinical features and the management strategies for rare coagulation factor deficiencies are discussed, little is known about them. This study was undertaken to assess the distribution, clinical presentation and treatment of patients with rare coagulation factor deficiency disorders in a cross-sectional population of India. Blood samples and other clinical details from patients suspected of rare coagulation factor deficiencies were collected by the Haemophilia Treatment Centers across India and were diagnosed at National Institute of Immunohaematology, Mumbai. A total of 321 cases of rare clotting factor deficiencies were diagnosed, of which 88% were severe, 10% moderate and 2% mild. Commonest deficiency encountered was factor XIII (FXIII) (30%) followed by FX (15.6%), FVII (15%), fibrinogen (12.1%), FXI (9%), combined V and VIII deficiency (5.6%) and congenital multiple vitamin K-dependent coagulation factor deficiency (MCFD, 2.1%). Major representation of these deficiencies was from Southern and Western India (82%). Mucocutaneous bleeding was the commonest clinical presentation (59%); intracranial (IC) haemorrhage was seen in 18% of the patients; menorrhagia was an important clinical pointer in women in the reproductive age group (78%); 8% of the severe cases had no history of bleeding and 73% of the FXIII deficiency cases had umbilical stump bleeding. The major therapeutic products used was fresh frozen plasma (64%), cryoprecipitate (15%), whole blood (15%), antifibrinolytics (5%) and recombinant FVIIa (1%). A distinct pattern in the distribution of rare clotting factor deficiencies was observed which was based on multiple factors that include ethnicity and the available diagnostic facilities in different regions of this vast country. © 2014 John Wiley & Sons Ltd.

  12. Nutritional deficiencies after bariatric surgery.

    Science.gov (United States)

    Bal, Bikram S; Finelli, Frederick C; Shope, Timothy R; Koch, Timothy R

    2012-09-01

    Lifestyle intervention programmes often produce insufficient weight loss and poor weight loss maintenance. As a result, an increasing number of patients with obesity and related comorbidities undergo bariatric surgery, which includes approaches such as the adjustable gastric band or the 'divided' Roux-en-Y gastric bypass (RYGB). This Review summarizes the current knowledge on nutrient deficiencies that can develop after bariatric surgery and highlights follow-up and treatment options for bariatric surgery patients who develop a micronutrient deficiency. The major macronutrient deficiency after bariatric surgery is protein malnutrition. Deficiencies in micronutrients, which include trace elements, essential minerals, and water-soluble and fat-soluble vitamins, are common before bariatric surgery and often persist postoperatively, despite universal recommendations on multivitamin and mineral supplements. Other disorders, including small intestinal bacterial overgrowth, can promote micronutrient deficiencies, especially in patients with diabetes mellitus. Recognition of the clinical presentations of micronutrient deficiencies is important, both to enable early intervention and to minimize long-term adverse effects. A major clinical concern is the relationship between vitamin D deficiency and the development of metabolic bone diseases, such as osteoporosis or osteomalacia; metabolic bone diseases may explain the increased risk of hip fracture in patients after RYGB. Further studies are required to determine the optimal levels of nutrient supplementation and whether postoperative laboratory monitoring effectively detects nutrient deficiencies. In the absence of such data, clinicians should inquire about and treat symptoms that suggest nutrient deficiencies.

  13. The Nature of Foot Ray Deficiency in Congenital Fibular Deficiency.

    Science.gov (United States)

    Reyes, Bryan A; Birch, John G; Hootnick, David R; Cherkashin, Alex M; Samchukov, Mikhail L

    Absent lateral osseous structures in congenital fibular deficiency, including the distal femur and fibula, have led some authors to refer to the nature of foot ray deficiency as "lateral" as well. Others have suggested that the ray deficiency is in the central portion of the midfoot and forefoot.We sought to determine whether cuboid preservation and/or cuneiform deficiency in the feet of patients with congenital fibular deficiency implied that the ray deficiency is central rather than lateral in patients with congenital fibular deficiency. We identified all patients with a clinical morphologic diagnosis of congenital fibular deficiency at our institution over a 15-year period. We reviewed the records and radiographs of patients who had radiographs of the feet to allow determination of the number of metatarsals, the presence or absence of a cuboid or calcaneocuboid fusion, the number of cuneiforms present (if possible), and any other osseous abnormalities of the foot. We excluded patients with 5-rayed feet, those who had not had radiographs of the feet, or whose radiographs were not adequate to allow accurate assessment of these radiographic features. We defined the characteristic "lateral (fifth) ray present" if there was a well-developed cuboid or calcaneocuboid coalition with which the lateral-most preserved metatarsal articulated. Twenty-six patients with 28 affected feet met radiographic criteria for inclusion in the study. All affected feet had a well-developed cuboid or calcaneocuboid coalition. The lateral-most ray of 25 patients with 26 affected feet articulated with the cuboid or calcaneocuboid coalition. One patient with bilateral fibular deficiency had bilateral partially deficient cuboids, and the lateral-most metatarsal articulated with the medial remnant of the deformed cuboids. Twenty-one of 28 feet with visible cuneiforms had 2 or 1 cuneiform. Although the embryology and pathogenesis of congenital fibular deficiency remain unknown, based on the

  14. MCAD deficiency in Denmark

    DEFF Research Database (Denmark)

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

    2012-01-01

    Medium-chain acyl-CoA dehydrogenase deficiency (MCADD) is the most common defect of fatty acid oxidation. Many countries have introduced newborn screening for MCADD, because characteristic acylcarnitines can easily be identified in filter paper blood spot samples by tandem mass spectrometry (MS...... analysis. This gives an incidence of MCADD detected by newborn screening in Denmark of 1/8954. In sharp contrast to this we found that the incidence of clinically presenting MCADD in Denmark in the 10 year period preceding introduction of MS/MS-based screening was only 1 in 39,691. This means that four...... lower proportion of newborns being homozygous for the prevalent disease-causing c.985A>G mutation. A significant number of the newborns have genotypes with mutations that have not been observed in patients detected clinically. Some of these mutations, like c.199T>C and c.127G>A, are always associated...

  15. Congenital fibular deficiency.

    Science.gov (United States)

    Hamdy, Reggie C; Makhdom, Asim M; Saran, Neil; Birch, John

    2014-04-01

    Congenital fibular deficiency (CFD) is characterized by a wide spectrum of manifestations ranging from mild limb length inequality (LLI) to severe shortening, with foot and ankle deformities and associated anomalies. The etiology of CFD remains unclear. Treatment goals are to achieve normal weight bearing, a functional plantigrade foot, and equal limb length. The recent Birch classification system has been proposed to provide a treatment guide: the functionality of the foot, LLI, and associated anomalies should be taken into account for decision-making. Treatment options include orthosis or epiphysiodesis, Syme or Boyd amputation and prosthetic rehabilitation, limb lengthening procedures, and foot and ankle reconstruction. The outcome of amputation for severe forms of CFD has shown favorable results and fewer complications compared with those of limb lengthening. Nevertheless, advances in the limb lengthening techniques may change our approach to treating patients with CFD and might extend the indications for reconstructive procedures to the treatment of severe LLI and foot deformities.

  16. Mortality and GH deficiency

    DEFF Research Database (Denmark)

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

    2007-01-01

    OBJECTIVE: To estimate the mortality in Denmark in patients suffering from GH deficiency (GHD). DESIGN: Mortality was analyzed in 1794 GHD patients and 8014 controls matched on age and gender. All records in GHD patients were studied and additional morbidity noted. Patients were divided...... into childhood onset (CO) and adult onset (AO), discriminated by an age cutoff below or above 18 years at onset of GHD. METHOD: Data on death were identified in national registries. Sex- and cause-specific mortalities were identified in CO and AO GHD when compared with controls. RESULTS: Mortality was increased...... versus AO males, both compared with controls (P mortality was increased due to cancer in all subgroups, due to circulatory diseases in all age groups for females and for males in the oldest age group. For CO, the increased mortality was due to cancer. CONCLUSIONS: We found...

  17. Micronutrient deficiencies in the pre-bariatric surgery.

    Science.gov (United States)

    de Lima, Karla Vanessa Gomes; Costa, Maria José de Carvalho; Gonçalves, Maria da Conceição Rodrigues; Sousa, Bruno Soares

    2013-01-01

    Data already demonstrated the increased prevalence of obesity in various segments of the population. In this context, bariatric surgery is accepted nowadays as the most effective tool in the treatment and control of morbid obesity. Several studies have evaluated the nutritional status after bariatric surgery, especially mixed by detecting a reduction in food intake of protein, vitamins and minerals. However, other studies have investigated the presence of nutritional deficiencies prior to surgery, which may be aggravated by the surgical procedure, resulting in serious postoperative complications. To analyze the literature in relationship to micronutrient deficiencies in obese patients before bariatric surgery. Was carried out a systematic review in several electronic databases, such as PubMed/ Medline, Scielo, Lilacs and Bireme. The following keywords were used alone or in combination: bariatric surgery, obesity, preoperative, gastric bypass, vitamin deficiencies, deficiencies and mineral nutrient absorption. Were included 40 review and original articles published between 2005 to 2012. There were consensus on the combination of preoperative nutritional deficiencies, restrictions and malabsorption, possibly induced by bariatric surgery that can lead patients to experience significant nutritional deficits during the late postoperative period, especially of micronutrients, resulting in serious complications. The high occurrence of micronutrient deficiencies preoperatively detected in morbidly obese candidates for bariatric surgery, plus a malabsorptive procedure, may involve worse prognosis during the late postoperative period. Preoperative evaluation of nutritional parameters and food intake is recommended in conjunction with surgical interventions.

  18. Iron deficiency and cardiovascular disease

    NARCIS (Netherlands)

    von Haehling, Stephan; Jankowska, Ewa A.; van Veldhuisen, Dirk J.; Ponikowski, Piotr; Anker, Stefan D.

    2015-01-01

    Iron deficiency affects up to one-third of the world's population, and is particularly common in elderly individuals and those with certain chronic diseases. Iron excess can be detrimental in cardiovascular illness, and research has now also brought anaemia and iron deficiency into the focus of

  19. Vitamin B12 deficiency anemia

    Science.gov (United States)

    ... provide oxygen to body tissues. There are many types of anemia. Vitamin B12 deficiency anemia is a low red ... People with this type of anemia often do well with treatment. Long-term vitamin B12 deficiency can cause nerve damage. This may be permanent if ...

  20. Iron deficiency anemia in children.

    Science.gov (United States)

    Subramaniam, Girish; Girish, Meenakshi

    2015-06-01

    Iron deficiency is not just anemia; it can be responsible for a long list of other manifestations. This topic is of great importance, especially in infancy and early childhood, for a variety of reasons. Firstly, iron need is maximum in this period. Secondly, diet in infancy is usually deficient in iron. Thirdly and most importantly, iron deficiency at this age can result in neurodevelopmental and cognitive deficits, which may not be reversible. Hypochromia and microcytosis in a complete blood count (CBC) makes iron deficiency anemia (IDA) most likely diagnosis. Absence of response to iron should make us look for other differential diagnosis like β thalassemia trait and anemia of chronic disease. Celiac disease is the most important cause of true IDA not responding to oral iron therapy. While oral ferrous sulphate is the cheapest and most effective therapy for IDA, simple nonpharmacological and pharmacological measures can go a long way in prevention of iron deficiency.

  1. Interactions between copper deficiency, selenium deficiency and adriamycin toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Fischer, J.; Tackett, R.; Johnson, M.A. (Univ. of Georgia, Athens (United States))

    1991-03-15

    The objective of this study was to test the hypothesis that there are interactions between copper (Cu) and selenium (Se) status, and adriamycin (ADR) toxicity. Male Sprague Dawley rats were fed Cu,Se adequate; Cu deficient, Se adequate ({minus}Cu); Cu adequate, Se deficient; or Cu,Se deficient diets for 38-41 days. ADR or saline (SAL) were administered weekly for the last 4 weeks of the study. Cu deficiency was confirmed by a 3-fold decrease in liver Cu,Zn-superoxide dismutase and liver Cu, and a 5-fold decrease in RBC Cu,Zn-SOD. Se deficiency was confirmed by a 10-fold decrease in liver glutathione peroxidase (GSH-Px). ADR, Cu deficiency and Se deficiency all caused EKG abnormalities. However, Cu and Se deficiencies did not enhance ADR's influence on EKGs. ADR increased lipid peroxidation in liver by 15% and in heart by 18% (NS). Cu deficiency decreased ADR-induced lipid peroxidation in heart tissue by 25%. ADR influenced Se status by significantly increasing heart GSH-Px, and Cu status by increasing liver Cu, plasma ceruloplasmin and liver Cu, Zn-SOD. These elevations in Cu,Zn-SOD and GSH-Px may be a consequence of the increased lipid peroxidation initiated by ADR. In {minus}Cu rats, ADR caused severe hemolytic anemia characterized by a 19% decrease in hematocrit and a 17-fold increase in splenic Fe. These data suggest that there are numerous interactions between ADR toxicity and Cu and Se status.

  2. [Nutritional deficiencies and supplementation after metabolic surgery].

    Science.gov (United States)

    Stroh, C; Meyer, F; Manger, T

    2016-09-01

    Increasing prevalence of morbid obesity in Germany is associated with an increasing number of bariatric surgical interventions.Based on the effectiveness of bariatric surgery with regard to a significant reduction of body weight and comorbidity as well as improvement of the quality of life compared with conservative measures, its value and impact has been substantially increased. Long-term metabolic deficits such as nutrient deficiencies can be considered the main risks of various restrictive, combined and malabsorptive procedures of bariatric surgery.The aim of this overview is to characterize metabolic complications after bariatric surgery and their prophylaxis, which require a temporary or permanent surveillance and, if necessary, effective supplementation.Bariatric surgical interventions such as gastric banding (GB) and sleeve gastrectomy (SG) can be subsequently associated with deficiencies related to B‑vitamins whereas iron, folate, and vitamins B1, B12 and D deficiencies might be consequences of malabsorptive procedures such as biliopancreatic diversion, duodenal switch and Roux-en-Y gastric bypass.Due to possible metabolic and surgical complications after bariatric surgery, patients need to undergo life-long follow-up investigations. The currently available guidelines of the American Association of Bariatric and Metabolic Surgery are the basis for the latest recommendations on supplementation and treatment in bariatric surgery.

  3. Deficiência de ferro na adolescência Iron deficiency in adolescence

    Directory of Open Access Journals (Sweden)

    Marlene P. Garanito

    2010-06-01

    Full Text Available A deficiência de ferro é o distúrbio nutricional mais comum no mundo e constitui a maior causa de anemia associada às condições onde há erro alimentar, perda crônica de sangue ou quando ocorre o crescimento rápido, como na infância, na gravidez e na adolescência. Esta deficiência acarreta prejuízos no desenvolvimento neuropsicomotor, na capacidade de aprendizagem, no apetite, no crescimento e na resposta do sistema imunológico. Na adolescência, além de com frequência observarmos hábitos alimentares inadequados, estão presentes intensas mudanças fisiológicas e psicossociais que, em associação, podem comprometer o crescimento e aumentar o risco do desenvolvimento de deficiência de ferro e outras carências nutricionais, sobretudo na fase púbere. Desta forma, o diagnóstico de deficiência de ferro entre os adolescentes deve ser lembrado a fim de que medidas possam ser tomadas para diminuir a incidência de anemia, do comprometimento do rendimento escolar e do sistema imunológico, neste período da vida.Iron deficiency is the most common nutritional disorder in the world and is a major cause of anemia associated with situations involving chronic blood loss or rapid growth such as during infancy, pregnancy and adolescence. This deficiency leads to impairment in psychomotor development, learning ability, appetite, growth and immune response. In adolescence, inadequate dietary habits are often observed and intensive physiological and psychological changes are seen that when combined can impair growth and increase the risk of developing iron deficiency or other nutritional disorders, especially during puberty. Thus, the diagnosis of iron deficiency among adolescents should always be considered so that measures can be taken to reduce the incidence of anemia, impairment of the immune system and improve school performance.

  4. Genetics Home Reference: adenosine deaminase 2 deficiency

    Science.gov (United States)

    ... Twitter Home Health Conditions Adenosine deaminase 2 deficiency Adenosine deaminase 2 deficiency Printable PDF Open All Close ... Javascript to view the expand/collapse boxes. Description Adenosine deaminase 2 (ADA2) deficiency is a disorder characterized ...

  5. Genetics Home Reference: lactate dehydrogenase deficiency

    Science.gov (United States)

    ... Facebook Twitter Home Health Conditions Lactate dehydrogenase deficiency Lactate dehydrogenase deficiency Printable PDF Open All Close All Enable Javascript to view the expand/collapse boxes. Description Lactate dehydrogenase deficiency is a condition that affects how the ...

  6. Genetics Home Reference: carnitine palmitoyltransferase I deficiency

    Science.gov (United States)

    ... SL, Raff ML. Novel mutations in CPT 1A define molecular heterogeneity of hepatic carnitine palmitoyltransferase I deficiency. ... What is newborn screening? New Pages type 2 diabetes mitochondrial complex I deficiency mitochondrial complex V deficiency ...

  7. Facts about Vitamin K Deficiency Bleeding

    Science.gov (United States)

    ... label> Information For… Media Policy Makers Facts about Vitamin K Deficiency Bleeding Recommend on Facebook Tweet Share Compartir ... deficient ” or has a “ vitamin deficiency ”. What is vitamin K and why is it important? Vitamin K is ...

  8. Genetics Home Reference: corticosterone methyloxidase deficiency

    Science.gov (United States)

    ... deficiency corticosterone methyloxidase deficiency Printable PDF Open All Close All Enable Javascript to view the expand/collapse boxes. ... methyloxidase deficiency can cause nausea, vomiting, dehydration, low blood pressure, extreme tiredness (fatigue), and muscle weakness. Affected infants ...

  9. Morbidity and GH deficiency

    DEFF Research Database (Denmark)

    Stochholm, Kirstine; Laursen, Torben; Green, Anders

    2008-01-01

    OBJECTIVE: To estimate morbidity in Denmark in all patients with GH deficiency (GHD). DESIGN: Morbidity was analyzed in 1794 GHD patients and 8014 controls matched on age and gender. All records in the GHD patients were studied and additional morbidity noted. Diagnoses and dates of admissions were...... identified in the National Patient Registry. Lag time until first admission was used as a measure of morbidity. Patients were divided into childhood onset (CO) and adult onset (AO), discriminated by an age cut-off of 18 years at onset of GHD. METHOD: Sex- and cause-specific hazard ratios (HRs) in CO and AO...... GHD compared with controls. RESULTS: Total morbidity was significantly increased in the GHD patients. HR for CO males: 3.1 (95% confidence interval (CI): 2.7-3.7), CO females: 3.2 (95% CI: 2.6-3.9), AO males: 2.9 (95% CI: 2.6-3.2), and AO females: 3.2 (95% CI: 2.8-3.6). In 18 out of 20 chapters from...

  10. SOD2 Deficient Erythroid Cells Up-Regulate Transferrin Receptor and Down-Regulate Mitochondrial Biogenesis and Metabolism

    Science.gov (United States)

    Martin, Florent M.; Xu, Xiuling; von Löhneysen, Katharina; Gilmartin, Timothy J.; Friedman, Jeffrey S.

    2011-01-01

    Background Mice irradiated and reconstituted with hematopoietic cells lacking manganese superoxide dismutase (SOD2) show a persistent hemolytic anemia similar to human sideroblastic anemia (SA), including characteristic intra-mitochondrial iron deposition. SA is primarily an acquired, clonal marrow disorder occurring in individuals over 60 years of age with uncertain etiology. Methodology/Principal Findings To define early events in the pathogenesis of this murine model of SA, we compared erythroid differentiation of Sod2-/- and normal bone marrow cells using flow cytometry and gene expression profiling of erythroblasts. The predominant transcriptional differences observed include widespread down-regulation of mitochondrial metabolic pathways and mitochondrial biogenesis. Multiple nuclear encoded subunits of complexes I-IV of the electron transport chain, ATP synthase (complex V), TCA cycle and mitochondrial ribosomal proteins were coordinately down-regulated in Sod2-/- erythroblasts. Despite iron accumulation within mitochondria, we found increased expression of transferrin receptor, Tfrc, at both the transcript and protein level in SOD2 deficient cells, suggesting deregulation of iron delivery. Interestingly, there was decreased expression of ABCb7, the gene responsible for X-linked hereditary SA with ataxia, a component required for iron-sulfur cluster biogenesis. Conclusions/Significance These results indicate that in erythroblasts, mitochondrial oxidative stress reduces expression of multiple nuclear genes encoding components of the respiratory chain, TCA cycle and mitochondrial protein synthesis. An additional target of particular relevance for SA is iron:sulfur cluster biosynthesis. By decreasing transcription of components of cluster synthesis machinery, both iron utilization and regulation of iron uptake are impacted, contributing to the sideroblastic phenotype. PMID:21326867

  11. SOD2 deficient erythroid cells up-regulate transferrin receptor and down-regulate mitochondrial biogenesis and metabolism.

    Directory of Open Access Journals (Sweden)

    Florent M Martin

    2011-02-01

    Full Text Available Mice irradiated and reconstituted with hematopoietic cells lacking manganese superoxide dismutase (SOD2 show a persistent hemolytic anemia similar to human sideroblastic anemia (SA, including characteristic intra-mitochondrial iron deposition. SA is primarily an acquired, clonal marrow disorder occurring in individuals over 60 years of age with uncertain etiology.To define early events in the pathogenesis of this murine model of SA, we compared erythroid differentiation of Sod2⁻/⁻ and normal bone marrow cells using flow cytometry and gene expression profiling of erythroblasts. The predominant transcriptional differences observed include widespread down-regulation of mitochondrial metabolic pathways and mitochondrial biogenesis. Multiple nuclear encoded subunits of complexes I-IV of the electron transport chain, ATP synthase (complex V, TCA cycle and mitochondrial ribosomal proteins were coordinately down-regulated in Sod2⁻/⁻ erythroblasts. Despite iron accumulation within mitochondria, we found increased expression of transferrin receptor, Tfrc, at both the transcript and protein level in SOD2 deficient cells, suggesting deregulation of iron delivery. Interestingly, there was decreased expression of ABCb7, the gene responsible for X-linked hereditary SA with ataxia, a component required for iron-sulfur cluster biogenesis.These results indicate that in erythroblasts, mitochondrial oxidative stress reduces expression of multiple nuclear genes encoding components of the respiratory chain, TCA cycle and mitochondrial protein synthesis. An additional target of particular relevance for SA is iron:sulfur cluster biosynthesis. By decreasing transcription of components of cluster synthesis machinery, both iron utilization and regulation of iron uptake are impacted, contributing to the sideroblastic phenotype.

  12. A deficiency of apoptosis inducing factor (AIF in Harlequin mouse heart mitochondria paradoxically reduces ROS generation during ischemia-reperfusion

    Directory of Open Access Journals (Sweden)

    Qun eChen

    2014-07-01

    Full Text Available Background and Aims: AIF (apoptosis inducing factor is a flavin and NADH containing protein located within mitochondria required for optimal function of the respiratory chain. AIF may function as an antioxidant within mitochondria, yet when released from mitochondria it activates caspase-independent cell death. The Harlequin (Hq mouse has a markedly reduced content of AIF, providing an experimental model to query if the main role of AIF in the exacerbation of cell death is enhanced mitochondrial generation of reactive oxygen species (ROS or the activation of cell death programs. We asked if the ROS generation is altered in Hq heart mitochondria at baseline or following ischemia-reperfusion (IR.Methods: Buffer perfused mouse hearts underwent 30 min ischemia and 30 min reperfusion. Mitochondrial function including oxidative phosphorylation and H2O2 generation was measured. Immunoblotting was used to determine the contents of AIF and PAR [poly(ADP-ribose] in cell fractions.Results: There were no differences in the release of H2O2 between wild type (WT and Hq heart mitochondria at baseline. IR increased H2O2 generation from WT but not from Hq mitochondria compared to corresponding time controls. The complex I activity was decreased in WT but not in Hq mice following IR. The relocation of AIF from mitochondria to nucleus was increased in WT but not in Hq mice. IR activated PARP-1 only in WT mice. Cell injury was decreased in Hq mouse heart following in vitro IR.Conclusion: A deficiency of AIF within mitochondria does not increase ROS production during IR, indicating that AIF functions less as an antioxidant within mitochondria. The decreased cardiac injury in Hq mouse heart accompanied by less AIF translocation to the nucleus suggests that AIF relocation, rather than the AIF content within mitochondria, contributes to cardiac injury during IR.

  13. Combined asymptomatic congenital anterior and posterior deficiency of the atlas

    Energy Technology Data Exchange (ETDEWEB)

    Hosalkar, H.S.; Gerardi, J.A.; Shaw, B.A. [Dept. of Pediatric Orthopedic Surgery, Valley Children' s Hospital, Madera, CA (United States)

    2001-11-01

    Atlas anomalies in terms of clefts and aplasia are rare. They can sometimes simulate fractures and need further evaluation. Imaging in terms of CT and MR can help resolve diagnostic confusion and also outline associated neurological involvement. A rare anomaly of anterior and posterior atlas arch, previously unclassified, is presented. (orig.)

  14. Genetics Home Reference: combined oxidative phosphorylation deficiency 1

    Science.gov (United States)

    ... 1 Patient Support and Advocacy Resources (5 links) American Liver Foundation Child Neurology Foundation: Mitochondrial Diseases Foundation for Mitochondrial Medicine MitoAction United Mitochondrial Disease Foundation Scientific Articles on PubMed (1 link) PubMed OMIM (1 ...

  15. Genetics Home Reference: phosphoglycerate kinase deficiency

    Science.gov (United States)

    ... Genetic Testing Registry: Phosphoglycerate kinase 1 deficiency Other Diagnosis and Management Resources (1 link) Children Living with Inherited Metabolic Diseases (CLIMB) (UK): Phosphoglycerate Kinase Deficiency (PDF) General Information ...

  16. Effects of tramadol, clonazepam, and their combination on brain mitochondrial complexes.

    Science.gov (United States)

    Mohamed, Tarek Mostafa; Ghaffar, Hamdy M Abdel; El Husseiny, Rabee M R

    2015-12-01

    The present study is an unsubstantiated qualitative assessment of the abused drugs-tramadol and clonazepam. The aim of this study is to evaluate whether the effects of tramadol, clonazepam, and their combination on mitochondrial electron transport chain (ETC) complexes were influential at therapeutic or at progressively increasing doses. The study comprised of a total of 70 healthy male rats, aged 3 months. According to the drug intake regimen, animals were divided into seven groups: control, tramadol therapeutic, clonazepam therapeutic, combination therapeutic, tramadol abuse, clonazepam abuse, and combination abuse group. At the end of the experiment, brain mitochondrial ETC complexes (I, II, III, and IV) were evaluated. Histopathological examinations were also performed on brain tissues. The results showed that groups that received tramadol (therapeutic and abuse) suffered from weight loss. Tramadol abuse group and combination abuse group showed significant decrease in the activities of I, III, and IV complexes but not in the activity of complex II. In conclusion, tramadol but not clonazepam has been found to partially inhibit the activities of respiratory chain complexes I, III, and IV but not the activity of complex II and such inhibition occurred only at doses that exceeded the maximum recommended adult human daily therapeutic doses. This result explains the clinical and histopathological effects of tramadol, such as seizures and red neurons (marker for apoptosis), respectively. © The Author(s) 2012.

  17. Copper deficiency alters cell bioenergetics and induces mitochondrial fusion through up-regulation of MFN2 and OPA1 in erythropoietic cells

    Energy Technology Data Exchange (ETDEWEB)

    Bustos, Rodrigo I.; Jensen, Erik L.; Ruiz, Lina M.; Rivera, Salvador; Ruiz, Sebastián [Center for Biomedical Research, Faculty of Biological Sciences and Faculty of Medicine, Universidad Andres Bello, Santiago (Chile); Simon, Felipe; Riedel, Claudia [Center for Biomedical Research, Faculty of Biological Sciences and Faculty of Medicine, Universidad Andres Bello, Santiago (Chile); Millennium Institute of Immunology and Immunotherapy, Santiago (Chile); Ferrick, David [Seahorse Bioscience, Billerica, MA (United States); Elorza, Alvaro A., E-mail: aelorza@unab.cl [Center for Biomedical Research, Faculty of Biological Sciences and Faculty of Medicine, Universidad Andres Bello, Santiago (Chile); Millennium Institute of Immunology and Immunotherapy, Santiago (Chile)

    2013-08-02

    Highlights: •In copper deficiency, cell proliferation is not affected. In turn, cell differentiation is impaired. •Enlarged mitochondria are due to up-regulation of MNF2 and OPA1. •Mitochondria turn off respiratory chain and ROS production. •Energy metabolism switch from mitochondria to glycolysis. -- Abstract: Copper is essential in cell physiology, participating in numerous enzyme reactions. In mitochondria, copper is a cofactor for respiratory complex IV, the cytochrome c oxidase. Low copper content is associated with anemia and the appearance of enlarged mitochondria in erythropoietic cells. These findings suggest a connection between copper metabolism and bioenergetics, mitochondrial dynamics and erythropoiesis, which has not been explored so far. Here, we describe that bathocuproine disulfonate-induced copper deficiency does not alter erythropoietic cell proliferation nor induce apoptosis. However it does impair erythroid differentiation, which is associated with a metabolic switch between the two main energy-generating pathways. That is, from mitochondrial function to glycolysis. Switching off mitochondria implies a reduction in oxygen consumption and ROS generation along with an increase in mitochondrial membrane potential. Mitochondrial fusion proteins MFN2 and OPA1 were up-regulated along with the ability of mitochondria to fuse. Morphometric analysis of mitochondria did not show changes in total mitochondrial biomass but rather bigger mitochondria because of increased fusion. Similar results were also obtained with human CD34+, which were induced to differentiate into red blood cells. In all, we have shown that adequate copper levels are important for maintaining proper mitochondrial function and for erythroid differentiation where the energy metabolic switch plus the up-regulation of fusion proteins define an adaptive response to copper deprivation to keep cells alive.

  18. Gastrin-releasing peptide receptor antagonist or N-acetylcysteine combined with omeprazol protect against mitochondrial complex II inhibition in a rat model of gastritis.

    Science.gov (United States)

    Rezin, Gislaine T; Petronilho, Fabricia C; Araújo, João H; Gonçalves, Cinara L; Daufenbach, Juliana F; Cardoso, Mariane R; Roesler, Rafael; Schwartsmann, Gilberto; Dal-Pizzol, Felipe; Streck, Emilio L

    2011-03-01

    The pathophysiology of gastritis involves an imbalance between gastric acid attack and mucosal defence. In addition, the gastric mucosal injury results in adenosine triphosphate (ATP) depletion leading to mitochondrial dysfunction. Several studies have shown the association of mitochondrial disorders with gastrointestinal dysfunction. In the present study, we investigated the activity of mitochondrial respiratory chain complexes activity in the stomach of rats with gastritis induced by indomethacin (IDM) and treated with omeprazole (OM), N-acetylcysteine (NAC) and the gastrin-releasing peptide receptor (GRPR) antagonist RC-3095. Adult male Wistar rats were pre-treated for 7 days with OM, NAC, RC-3095, combination of OM plus RC-3095, OM plus NAC and water (control). The animals were then submitted to fasting for 24 hr; IDM was administered. The rats were killed 6 hr later, and the stomachs were used for evaluation of macroscopic damage and respiratory chain activity. Our results showed that complex I and IV activities were not affected by administration of IDM. On the other hand, complex II and III activities were inhibited. In addition, OM plus RC-3095 and OM plus NAC did not reverse complex II activity inhibition. However, the complex III activity inhibition was reversed only with the combined use of OM plus RC-3095 and OM plus NAC. Our results are in agreement with previous studies indicating mitochondrial dysfunction in the pathophysiology of gastrointestinal tract disease and we suggest that GRPR antagonism might be a novel therapeutic strategy in gastritis. © 2010 The Authors. Basic & Clinical Pharmacology & Toxicology © 2010 Nordic Pharmacological Society.

  19. Possibilities of Correction for Iron Deficiency and Intestinal Microbiocenosis Disorders in Children

    Directory of Open Access Journals (Sweden)

    L.V. Kvashnina

    2016-09-01

    Full Text Available Iron deficiencies and intestinal microbiocenosis disorders in children are the most urgent problems in pediatrics. The article presents the data of our own researches on the effectiveness of the correction for iron deficiency anemia in children with intestinal microbiocenosis disorders during the combination use of iron supplements and spore-forming probiotic Lactovit Forte.

  20. Genetics Home Reference: CLPB deficiency

    Science.gov (United States)

    ... or severe CLPB deficiency have clouding of the lenses of the eyes ( cataracts ) from birth (congenital) or ... Lung Cancer Awareness Month Celebrating National Family Health History Day All Bulletins Features What are genome editing ...

  1. Reconstructive surgery for fibular deficiency.

    Science.gov (United States)

    Shatilov, O E; Rozkov, A V; Cheminova, T V

    1991-08-01

    Three types of fibular deficiency are described which determine the nature of the surgery and prosthesis required. The surgical management of 50 patients who had a total of 103 operations is described.

  2. [Niacin deficiency and cutaneous immunity].

    Science.gov (United States)

    Ikenouchi-Sugita, Atsuko; Sugita, Kazunari

    2015-01-01

    Niacin, also known as vitamin B3, is required for the synthesis of coenzymes, nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP). Niacin binds with G protein-coupled receptor (GPR) 109A on cutaneous Langerhans cells and causes vasodilation with flushing in head and neck area. Niacin deficiency due to excessive alcohol consumption, certain drugs or inadequate uptake in diet causes pellagra, a photosensitivity dermatitis. Recently several studies have revealed the mechanism of photosensitivity in niacin deficiency, which may pave a way for new therapeutic approaches. The expression level of prostaglandin E synthase (PTGES) is up-regulated in the skin of both pellagra patients and niacin deficient pellagra mouse models. In addition, pellagra is mediated through prostaglandin E₂-EP4 (PGE₂-EP4) signaling via reactive oxygen species (ROS) production in keratinocytes. In this article, we have reviewed the role of niacin in immunity and the mechanism of niacin deficiency-induced photosensitivity.

  3. Iron deficiency among blood donors

    DEFF Research Database (Denmark)

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

    2017-01-01

    and menopausal status are the strongest predictors of iron deficiency. Only little information on the health effects of iron deficiency in blood donors exits. Possibly, after a standard full blood donation, a temporarily reduced physical performance for women is observed. However, iron deficiency among blood...... donors is not reflected in a reduced self-perceived mental and physical health. In general, the high proportion of iron-deficient donors can be alleviated either by extending the inter-donation intervals or by guided iron supplementation. The experience from Copenhagen, the Capital Region of Denmark......, is that routine ferritin measurements and iron supplementation are feasible and effective ways of reducing the proportion of donors with low haemoglobin levels....

  4. Vitamin B12 deficiency presenting with Myeloneuropathy | Kolapo ...

    African Journals Online (AJOL)

    The neurologic manifestations of vitamin B12 deficiency, although uncommon, are the result of its effects on the brain, optic nerves, peripheral nerves, and spinal cord. Myeloneuropathy, resulting in sensory disturbances, weakness, and spasticity, is known as subacute combined degeneration and primarily involves the ...

  5. Immune Deficiency Disease' of Undetermined Aetiology in Infancy

    African Journals Online (AJOL)

    1974-04-06

    Apr 6, 1974 ... Immunodeficiency diseases in infancy may be genetic or may result from an infection acquired during intra- uterine life. A precise aetiological diagnosis is important for genetic counselling purposes, prognosis and treatment. The case of a young female child with a combined immuno- deficiency disease ...

  6. Kinematic characteristics of anterior cruciate ligament deficient knees with concomitant meniscus deficiency during ascending stairs.

    Science.gov (United States)

    Zhang, Yu; Huang, Wenhan; Ma, Limin; Lin, Zefeng; Huang, Huayang; Xia, Hong

    2017-02-01

    It is commonly believed that a torn ACL or a damaged meniscus may be associated with altered knee joint movements. The purpose of this study was to measure the tibiofemoral kinematics of ACL deficiency with concomitant meniscus deficiency. Unilateral knees of 28 ACL deficient participants were studied while ascending stairs. Among these patients, 6 had isolated ACL injuries (group I), 8 had combined ACL and medial meniscus injuries (group II), 8 had combined ACL and lateral meniscus injuries (group III) and 6 had combined ACL and medial-lateral meniscus injuries (group IV). Both knees were then scanned during a stair climb activity using single fluoroscopic image system. Knee kinematics were measured at 0°, 5°, 10°, 15°, 30° and 60° of flexion during ascending stairs. At 0°, 15° and 30° flexion of the knee, the tibia rotated externally by 13.9 ± 6.1°,13.8 ± 9.5° and 15.9 ± 9.8° in Group I. Group II and III exhibited decreased external rotation from 60° to full extension. Statistical differences were found in 0°, 15°and 30° of flexion for the 2 groups compared with Group I. In general, the tibia showed anterior translation with respect to the femur during ascending stairs. It was further determined that Group III had larger anterior translation compared with Group IV at 0° and 5° of flexion (-6.9 ± 1.7 mm vs. 6.2 ± 11.3 mm, P = 0.041; -9.0 ± 1.8 mm vs. 8.1 ± 13.4 mm, P = 0.044). During ascending stairs the ACL deficient knee with different deficiencies in the meniscus will show significantly different kinematics compared with that of uninjured contralateral knee. Considering the varying effect of meniscus injuries on knee joint kinematics, future studies should concentrate on specific treatment of patients with combined ACL and meniscus injuries to protect the joint from abnormal kinematics and subsequent postoperative degeneration.

  7. Iron deficiency and cognitive functions

    OpenAIRE

    Jáuregui-Lobera, Ignacio

    2014-01-01

    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...

  8. Autophagy induction by tetrahydrobiopterin deficiency

    Science.gov (United States)

    Kwak, Sang Su; Suk, Jinkyu; Choi, Ji Hye; Yang, Seungkyung; Kim, Jin Woo; Sohn, Seonghyang; Chung, Jae Hoon; Hong, Yong Hee; Lee, Dong Hwan; Ahn, Jeong Keun; Min, Hyesun; Fu, Ya-Min; Meadows, Gary G

    2011-01-01

    Tetrahydrobiopterin (BH4) deficiency is a genetic disorder associated with a variety of metabolic syndromes such as phenylketonuria (PKU). In this article, the signaling pathway by which BH4 deficiency inactivates mTORC1 leading to the activation of the autophagic pathway was studied utilizing BH4-deficient Spr-/- mice generated by the knockout of the gene encoding sepiapterin reductase (SR) catalyzing BH4 synthesis. We found that mTORC1 signaling was inactivated and autophagic pathway was activated in tissues from Spr-/- mice. This study demonstrates that tyrosine deficiency causes mTORC1 inactivation and subsequent activation of autophagic pathway in Spr-/- mice. Therapeutic tyrosine diet completely rescued dwarfism and mTORC1 inhibition but inactivated autophagic pathway in Spr-/- mice. Tyrosine-dependent inactivation of mTORC1 was further supported by mTORC1 inactivation in Pahenu2 mouse model lacking phenylalanine hydroxylase (Pah). NIH3T3 cells grown under the condition of tyrosine restriction exhibited autophagy induction. However, mTORC1 activation by RhebQ64L, a positive regulator of mTORC1, inactivated autophagic pathway in NIH3T3 cells under tyrosine-deficient conditions. In addition, this study first documents mTORC1 inactivation and autophagy induction in PKU patients with BH4 deficiency. PMID:21795851

  9. Adenosine Deaminase Deficiency - More Than Just an Immunodeficiency

    Directory of Open Access Journals (Sweden)

    Kathryn Victoria Whitmore

    2016-08-01

    Full Text Available Adenosine deaminase (ADA deficiency is best known as a form of severe combined immunodeficiency (SCID which results from mutations in the gene encoding adenosine deaminase. Affected patients present with clinical and immunological manifestations typical of a severe combined immunodeficiency. Therapies are currently available that can that target these immunological disturbances and treated patients show varying degrees of clinical improvement. However, there is now a growing body of evidence that deficiency of ADA has significant impact on non-immunological organ systems. This review will outline the impact of ADA deficiency on various organ systems, starting with the well understood immunological abnormalities. We will discuss possible pathogenic mechanisms and also highlight ways in which current treatments could be improved. In doing so, we aim to present ADA deficiency as more than an immunodeficiency and suggest that it should be recognized as a systemic metabolic disorder that affects multiple organ systems. Only by fully understanding ADA deficiency and its manifestations in all organ systems can we aim to deliver therapies that will correct all the clinical consequences.

  10. Differential Diagnosis of Primary and Secondary Hyperparathyroidism Caused by Vitamin D Deficiency

    Directory of Open Access Journals (Sweden)

    S.M. Cherenko

    2015-08-01

    Conclusions. Short ergocalciferol treatment can be a valuable and reliable clinical method to differentiate isolated vitamin D deficiency and asymptomatic primary hyperparathyroidism combined with a lack of vitamin D.

  11. Reversible Myelopathy on Magnetic Resonance Imaging Due to Cobalamin Deficiency

    Directory of Open Access Journals (Sweden)

    Wei-Ju Lee

    2008-07-01

    Full Text Available Subacute combined degeneration (SCD is known as myelopathy due to vitamin B12 deficiency. SCD always involves the posterior and lateral columns of the spinal cord, with the neuropathologic change showing vacuolation of the white matter. We describe 2 patients who presented with ataxic gait, impaired proprioception over limbs, and even mental change due to vitamin B12 deficiency. Magnetic resonance imaging (MRI of the cervical spine showed increased signal intensity on T2-weighted imaging, and laboratory data showed low serum vitamin B12 level. The 2 patients were treated with vitamin B12 injection intramuscularly. There was clinical improvement after treatment along with normalization of the MRI.

  12. Methylenetetrahydrofolate reductase (MTHFR) deficiency presenting as a rash.

    LENUS (Irish Health Repository)

    Crushell, Ellen

    2012-09-01

    We report on the case of a 2-year-old girl recently diagnosed with Methylenetetrahydrofolate reductase (MTHFR) deficiency who originally presented in the neonatal period with a distinctive rash. At 11 weeks of age she developed seizures, she had acquired microcephaly and developmental delay. The rash deteriorated dramatically following commencement of phenobarbitone; both rash and seizures abated following empiric introduction of pyridoxine and folinic acid as treatment of possible vitamin responsive seizures. We postulate that phenobarbitone in combination with MTHFR deficiency may have caused her rash to deteriorate and subsequent folinic acid was helpful in treating the rash and preventing further acute neurological decline as commonly associated with this condition.

  13. Class switch recombination in selective IgA-deficient subjects

    DEFF Research Database (Denmark)

    Jensen, Lone Hummelshøj; Ryder, L P; Nielsen, L K

    2006-01-01

    control donors, all Caucasians. Stimulation of B cells from IgA-deficient donors with the cytokines transforming growth factor (TGF)-beta, interferon (IFN)-gamma or interleukin (IL)-10 in the presence of anti-CD40 antibodies showed reduced expression of both activation-induced cytidine deaminase (AID...... IL-4 to TGF-beta alone or in combination with IL-10, the immunoglobulin production in B cells from IgA-deficient donors was comparable with those of normal controls. These data show that in healthy subjects in vitro IgA production can be up-regulated by addition of IL-10 to CD40-stimulated B cells...

  14. [Xanthine oxidase deficiency (hereditary xanthinuria), molybdenum cofactor deficiency].

    Science.gov (United States)

    Sumi, S; Wada, Y

    1996-12-01

    Hereditary xanthinuria is a rare autosomal recessive disorder, with xanthine oxidase deficiency. Patients often display renal symptoms because they excrete a large amounts of xanthine in urine. An high-fluid-intake, alow-purine-food, and alkalinization of urine are effective in the patients. Molybdenum cofactor is essential for xanthine oxidase, sulfite oxidase and aldehyde oxidase. Patients with molybdenum cofactor deficiency display severe neurological symptoms, such as severe convulsions. The patients increase urinary excretions of xanthine and sulfite. Treatments are ineffective for neurological symptoms.

  15. Iron deficiency and bariatric surgery.

    Science.gov (United States)

    Jáuregui-Lobera, Ignacio

    2013-05-15

    It is estimated that the prevalence of anaemia in patients scheduled for bariatric surgery is higher than in the general population and the prevalence of iron deficiencies (with or without anaemia) may be higher as well. After surgery, iron deficiencies and anaemia may occur in a higher percentage of patients, mainly as a consequence of nutrient deficiencies. In addition, perioperative anaemia has been related with increased postoperative morbidity and mortality and poorer quality of life after bariatric surgery. The treatment of perioperative anaemia and nutrient deficiencies has been shown to improve patients' outcomes and quality of life. All patients should undergo an appropriate nutritional evaluation, including selective micronutrient measurements (e.g., iron), before any bariatric surgical procedure. In comparison with purely restrictive procedures, more extensive perioperative nutritional evaluations are required for malabsorptive procedures due to their nutritional consequences. The aim of this study was to review the current knowledge of nutritional deficits in obese patients and those that commonly appear after bariatric surgery, specifically iron deficiencies and their consequences. As a result, some recommendations for screening and supplementation are presented.

  16. Leaf Senescence by Magnesium Deficiency

    Directory of Open Access Journals (Sweden)

    Keitaro Tanoi

    2015-12-01

    Full Text Available Magnesium ions (Mg2+ are the second most abundant cations in living plant cells, and they are involved in various functions, including photosynthesis, enzyme catalysis, and nucleic acid synthesis. Low availability of Mg2+ in an agricultural field leads to a decrease in yield, which follows the appearance of Mg-deficient symptoms such as chlorosis, necrotic spots on the leaves, and droop. During the last decade, a variety of physiological and molecular responses to Mg2+ deficiency that potentially link to leaf senescence have been recognized, allowing us to reconsider the mechanisms of Mg2+ deficiency. This review focuses on the current knowledge about the physiological responses to Mg2+ deficiency including a decline in transpiration, accumulation of sugars and starch in source leaves, change in redox states, increased oxidative stress, metabolite alterations, and a decline in photosynthetic activity. In addition, we refer to the molecular responses that are thought to be related to leaf senescence. With these current data, we give an overview of leaf senescence induced by Mg deficiency.

  17. Iron Deficiency and Bariatric Surgery

    Directory of Open Access Journals (Sweden)

    Ignacio Jáuregui-Lobera

    2013-05-01

    Full Text Available It is estimated that the prevalence of anaemia in patients scheduled for bariatric surgery is higher than in the general population and the prevalence of iron deficiencies (with or without anaemia may be higher as well. After surgery, iron deficiencies and anaemia may occur in a higher percentage of patients, mainly as a consequence of nutrient deficiencies. In addition, perioperative anaemia has been related with increased postoperative morbidity and mortality and poorer quality of life after bariatric surgery. The treatment of perioperative anaemia and nutrient deficiencies has been shown to improve patients’ outcomes and quality of life. All patients should undergo an appropriate nutritional evaluation, including selective micronutrient measurements (e.g., iron, before any bariatric surgical procedure. In comparison with purely restrictive procedures, more extensive perioperative nutritional evaluations are required for malabsorptive procedures due to their nutritional consequences. The aim of this study was to review the current knowledge of nutritional deficits in obese patients and those that commonly appear after bariatric surgery, specifically iron deficiencies and their consequences. As a result, some recommendations for screening and supplementation are presented.

  18. Human Coenzyme Q10 Deficiency

    Science.gov (United States)

    Quinzii, Catarina M.; DiMauro, Salvatore

    2006-01-01

    Ubiquinone (coenzyme Q10 or CoQ10) is a lipid-soluble component of virtually all cell membranes and has multiple metabolic functions. Deficiency of CoQ10 (MIM 607426) has been associated with five different clinical presentations that suggest genetic heterogeneity, which may be related to the multiple steps in CoQ10 biosynthesis. Patients with all forms of CoQ10 deficiency have shown clinical improvements after initiating oral CoQ10 supplementation. Thus, early diagnosis is of critical importance in the management of these patients. This year, the first molecular defect causing the infantile form of primary human CoQ10 deficiency has been reported. The availability of genetic testing will allow for a better understanding of the pathogenesis of this disease and early initiation of therapy (even presymptomatically in siblings of patients) in this otherwise life-threatening infantile encephalomyopathy. PMID:17094036

  19. [Metachromatic leukodystrophy (MLD) and Multiple sulphatase deficiency (MSD)].

    Science.gov (United States)

    Eto, Y; Hasegawa, Y; Tsuda, T

    1995-12-01

    MLD is caused by a deficiency of arylsulfatase A and hence sulfolipids are accumulated in various patient's tissues. Various clinical phenotypes including activator deficiency, pseudodeficiency and MSD. Recently, molecular basis of these disorders have been identified. Clinical phenotype in MLD is well correlated with their genotype. Most common mutation in Caucasian MLD is caused by 609A mutation which produces late infantile MLD. In Japanese, most common mutation is 445A mutation. Essential treatment of MLD is recently carried out by bone marrow transplantation. On the hand, MSD is caused by multiple deficiencies of various sulfatases and hence accumulated various sulfated compounds such as sulfatide and acid mucopolysaccharides. The clinical features have combined characteristics of MLD and mucopolysaccharidosis. The cause of this disorder is recently identified as abnormal modification of various sulfatase.

  20. Differential diagnosis of iron deficiency

    OpenAIRE

    Vicari, Perla [UNIFESP; Figueiredo, Maria Stella [UNIFESP

    2010-01-01

    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 dura...

  1. Newborn screening for MCAD deficiency

    DEFF Research Database (Denmark)

    Horvath, Gabriella A; Davidson, A G F; Stockler-Ipsiroglu, Sylvia G

    2008-01-01

    BACKGROUND: Medium Chain Acyl-CoA Dehydrogenase (MCAD) Deficiency is an autosomal recessive disorder of fatty acid oxidation, with potential fatal outcome. MCAD deficiency is diagnosed by acylcarnitine analysis on newborn screening blood spot cards by tandem mass spectrometry. Early diagnosis...... length acylcarnitines, octanoylcarnitine (C8) and decanoylcarnitine (C10), were measured on newborn screening blood spot cards. Out of 121,000 live births, 17 newborns had C8 values above the screening cut-off of 0.38 umol/L. Ten newborns had elevated C8 on repeat cards and were investigated further...

  2. [Nutritional deficiencies associated with bariatric surgery].

    Science.gov (United States)

    Folope, Vanessa; Coëffier, Moïse; Déchelotte, Pierre

    2007-04-01

    Morbidly obese patients often have nutritional deficiencies, particularly in fat-soluble vitamins, folic acid and zinc. After bariatric surgery, these deficiencies may increase and others can appear, especially because of the limitation of food intake in gastric reduction surgery and of malabsorption in by-pass procedures. The latter result in more important weight loss but also increase the risk of more severe deficiencies. The protein deficiency associated with a decrease in the fat-free mass has been described in both procedures. It can sometimes require an enteral or parenteral support. Anemia can be secondary to iron deficiency, folic acid deficiency and even to vitamin B12 deficiency. Neurological disorders such as Gayet-Wernicke encephalopathy due to thiamine deficiency, or peripheral neuropathies may also be observed. Malabsorption of fat-soluble vitamins and other nutrients, especially if diagnosed after by-pass surgery, rarely cause clinical symptoms. However, some complications have been reported such as bone demineralization due to vitamin D deficiency, hair loss secondary to zinc deficiency or hemeralopia from vitamin A deficiency. A careful nutritional follow-up should be performed during pregnancy after obesity surgery, because possible deficiencies can affect the health of both the mother and child. In conclusion, increased awareness of the risk of deficiency and the systematic dosage of micronutrients are needed in the pre- and postoperative period in obese patients undergoing bariatric surgery. The case by case correction of these deficiencies is mandatory, and their systematic prevention should be evaluated.

  3. Interactions between zinc deficiency and environmental enteropathy in developing countries.

    Science.gov (United States)

    Lindenmayer, Greta W; Stoltzfus, Rebecca J; Prendergast, Andrew J

    2014-01-01

    Zinc deficiency affects one-fifth of the world's population and leads to substantial morbidity and mortality. Environmental enteropathy (EE), a subclinical pathology of altered intestinal morphology and function, is almost universal among people living in developing countries and affects long-term growth and health. This review explores the overlapping nature of these 2 conditions and presents evidence for their interaction. EE leads to impaired zinc homeostasis, predominantly due to reduced absorptive capacity arising from disturbed intestinal architecture, and zinc deficiency exacerbates several of the proposed pathways that underlie EE, including intestinal permeability, enteric infection, and chronic inflammation. Ongoing zinc deficiency likely perpetuates the adverse outcomes of EE by worsening malabsorption, reducing intestinal mucosal immune responses, and exacerbating systemic inflammation. Although the etiology of EE is predominantly environmental, zinc deficiency may also have a role in its pathogenesis. Given the impact of both EE and zinc deficiency on morbidity and mortality in developing countries, better understanding the relation between these 2 conditions may be critical for developing combined interventions to improve child health.

  4. Pitfalls in the diagnosis of multiple sulfatase deficiency.

    Science.gov (United States)

    Mancini, G M; van Diggelen, O P; Huijmans, J G; Stroink, H; de Coo, R F

    2001-02-01

    Multiple sulfatase deficiency (MSD, OMIM 272200) is an autosomal recessive leukodystrophy associated with the deficiency of several, in total seven, sulfatases. The disorder is clinically and biochemically variable. The clinical picture combines features of mucopolysaccharidosis and metachromatic leukodystrophy (MLD, OMIM 250100) in a variable spectrum. Here we report a 3-year old Iranian girl with an MLD-like presentation of MSD. Arylsulfatase A deficiency and sulfatide excretion were found. Differently from what was previously reported in the literature, this girl never showed abnormal mucopolysaccharide excretion in the urine. There were no additional visceral or skeletal signs. She was originally diagnosed as having MLD. Only when she developed ichthyosis were seven additional sulfatases measured. In leukocytes, arylsulfatase A, steroid sulfatase and N-acetylglucosamine-6 sulfatase were profoundly deficient, while iduronate-2 sulfatase and arylsulfatase B were moderately reduced. In fibroblasts, N-acetylglucosamine-6 sulfatase was deficient, while arylsulfatase A was moderately reduced. This case illustrates the possible pitfalls in the clinical and laboratory diagnosis of MSD.

  5. Potential of essential fatty acid deficiency with extremely low fat diet in lipoprotein lipase deficiency during pregnancy: A case report

    Directory of Open Access Journals (Sweden)

    Anderson Gregory J

    2004-12-01

    Full Text Available Abstract Background Pregnancy in patients with lipoprotein lipase deficiency is associated with high risk of maternal pancreatitis and fetal death. A very low fat diet ( Case presentation A 23 year-old gravida 1 woman with primary lipoprotein lipase deficiency was seen at 7 weeks of gestation in the Lipid Clinic for management of severe hypertriglyceridemia that had worsened with pregnancy. While on her habitual fat intake of 10% of total calories, her pregnancy resulted in an exacerbation of the hypertriglyceridemia, which prompted further restriction of fat intake to Conclusions An extremely low fat diet in combination with topical sunflower oil and gemfibrozil administration was safely implemented in pregnancy associated with the severe hypertriglyceridemia of lipoprotein lipase deficiency.

  6. Educational paper: Primary antibody deficiencies

    NARCIS (Netherlands)

    G.J.A. Driessen (Gertjan); M. van der Burg (Mirjam)

    2011-01-01

    textabstractPrimary antibody deficiencies (PADs) are the most common primary immunodeficiencies and are characterized by a defect in the production of normal amounts of antigen-specific antibodies. PADs represent a heterogeneous spectrum of conditions, ranging from often asymptomatic selective IgA

  7. Diagnosis of factor VIII deficiency.

    NARCIS (Netherlands)

    Verbruggen, B.; Meijer, P.; Novakova, I.; Heerde, W. Van

    2008-01-01

    The correct diagnosis of factor VIII deficiency and the assessment of severity of the disease are essential for a patient-tailored treatment strategy. An optimal diagnostic procedure comprises sensitive and specific screening methods and factor VIII activity assays. Different screening reagents show

  8. 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.

  9. Iron deficiency anemia in children

    Directory of Open Access Journals (Sweden)

    Pochinok T.V.

    2016-05-01

    Full Text Available In the article the role of iron in the human body is highlighted. The mechanism of development of iron deficiency states, their consequences and the basic principles of diagnosis and correction of children of different ages are shown.

  10. ALPHA,·ANTITRYPSIN DEFICIENCY*

    African Journals Online (AJOL)

    1971-02-06

    Feb 6, 1971 ... The association between homozygous alpha,-antitrypsin deficiency and chronic obstructive pulmonary disease was first described by Laurell and Eriksson in 1963' and since then numerous reports have confirmed and extended their observations. The concept envisages a relatively uninhi- bited proteolytic ...

  11. Carnitine palmityl transferase I deficiency

    NARCIS (Netherlands)

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

    2001-01-01

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

  12. Epigenetic Deficiencies and Replicative Stress

    DEFF Research Database (Denmark)

    Shoaib, Muhammad; Sørensen, Claus Storgaard

    2015-01-01

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

  13. Preventing Iron Deficiency and Anaemia

    African Journals Online (AJOL)

    Siegal_D

    Iron-deficient older children and adults have poorer-than-normal ability to concentrate or do physical work for ... and baby, delays menstruation. ▫ young children should not be fed unfortified commercial milk. ... vegetables, millet, sorghum and legumes. • Avoid drinking tea or coffee with or soon after meals. Do not give tea ...

  14. PREPL deficiency: delineation of the phenotype and development of a functional blood assay.

    Science.gov (United States)

    Régal, Luc; Mårtensson, Emma; Maystadt, Isabelle; Voermans, Nicol; Lederer, Damien; Burlina, Alberto; Juan Fita, María Jesús; Hoogeboom, A Jeannette M; Olsson Engman, Mia; Hollemans, Tess; Schouten, Meyke; Meulemans, Sandra; Jonson, Tord; François, Inge; Gil Ortega, David; Kamsteeg, Erik-Jan; Creemers, John W M

    2017-07-20

    PurposePREPL deficiency causes neonatal hypotonia, ptosis, neonatal feeding difficulties, childhood obesity, xerostomia, and growth hormone deficiency. Different recessive contiguous gene deletion syndromes involving PREPL and a variable combination of SLC3A1 (hypotonia-cystinuria syndrome), CAMKMT (atypical hypotonia-cystinuria syndrome), and PPM1B (2p21 deletion syndrome) have been described. In isolated PREPL deficiency, previously described only once, the absence of cystinuria complicates the diagnosis. Therefore, we developed a PREPL blood assay and further delineated the phenotype.MethodsClinical features of new subjects with PREPL deficiency were recorded. The presence of PREPL in lymphocytes and its reactivity with an activity-based probe were evaluated by western blot.ResultsFive subjects with isolated PREPL deficiency, three with hypotonia-cystinuria syndrome, and two with atypical hypotonia-cystinuria syndrome had nine novel alleles. Their IQs ranged from 64 to 112. Adult neuromuscular signs included ptosis, nasal dysarthria, facial weakness, and variable proximal and neck flexor weakness. Autonomic features are prevalent. PREPL protein and reactivity were absent in lymphocytes from subjects with PREPL deficiency, but normal in the clinically similar Prader-Willi syndrome.ConclusionPREPL deficiency causes neuromuscular, autonomic, cognitive, endocrine, and dysmorphic clinical features. PREPL is not deficient in Prader-Willi syndrome. The novel blood test should facilitate the confirmation of PREPL deficiency.GENETICS in MEDICINE advance online publication, 20 July 2017; doi:10.1038/gim.2017.74.

  15. Vitamin B12 deficiency from the perspective of a practicing hematologist.

    Science.gov (United States)

    Green, Ralph

    2017-05-11

    B12 deficiency is the leading cause of megaloblastic anemia, and although more common in the elderly, can occur at any age. Clinical disease caused by B12 deficiency usually connotes severe deficiency, resulting from a failure of the gastric or ileal phase of physiological B12 absorption, best exemplified by the autoimmune disease pernicious anemia. There are many other causes of B12 deficiency, which range from severe to mild. Mild deficiency usually results from failure to render food B12 bioavailable or from dietary inadequacy. Although rarely resulting in megaloblastic anemia, mild deficiency may be associated with neurocognitive and other consequences. B12 deficiency is best diagnosed using a combination of tests because none alone is completely reliable. The features of B12 deficiency are variable and may be atypical. Timely diagnosis is important, and treatment is gratifying. Failure to diagnose B12 deficiency can have dire consequences, usually neurological. This review is written from the perspective of a practicing hematologist. © 2017 by The American Society of Hematology.

  16. Iron refractory iron deficiency anemia

    Science.gov (United States)

    De Falco, Luigia; Sanchez, Mayka; Silvestri, Laura; Kannengiesser, Caroline; Muckenthaler, Martina U.; Iolascon, Achille; Gouya, Laurent; Camaschella, Clara; Beaumont, Carole

    2013-01-01

    Iron refractory iron deficiency anemia is a hereditary recessive anemia due to a defect in the TMPRSS6 gene encoding Matriptase-2. This protein is a transmembrane serine protease that plays an essential role in down-regulating hepcidin, the key regulator of iron homeostasis. Hallmarks of this disease are microcytic hypochromic anemia, low transferrin saturation and normal/high serum hepcidin values. The anemia appears in the post-natal period, although in some cases it is only diagnosed in adulthood. The disease is refractory to oral iron treatment but shows a slow response to intravenous iron injections and partial correction of the anemia. To date, 40 different Matriptase-2 mutations have been reported, affecting all the functional domains of the large ectodomain of the protein. In vitro experiments on transfected cells suggest that Matriptase-2 cleaves Hemojuvelin, a major regulator of hepcidin expression and that this function is altered in this genetic form of anemia. In contrast to the low/undetectable hepcidin levels observed in acquired iron deficiency, in patients with Matriptase-2 deficiency, serum hepcidin is inappropriately high for the low iron status and accounts for the absent/delayed response to oral iron treatment. A challenge for the clinicians and pediatricians is the recognition of the disorder among iron deficiency and other microcytic anemias commonly found in pediatric patients. The current treatment of iron refractory iron deficiency anemia is based on parenteral iron administration; in the future, manipulation of the hepcidin pathway with the aim of suppressing it might become an alternative therapeutic approach. PMID:23729726

  17. 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.

  18. Genetics Home Reference: congenital leptin deficiency

    Science.gov (United States)

    ... Obesity? National Institute of Diabetes and Digestive and Kidney Diseases: Active at Any Size! Educational Resources (6 links) Centers for Disease Control and Prevention: Obesity and Genetics MalaCards: congenital leptin deficiency Orphanet: Obesity due to congenital leptin deficiency ...

  19. Diagnosis of vitamin B12 deficiency.

    OpenAIRE

    HU, Rehman

    1984-01-01

    Vitamin B12 (cobalamin) deficiency occurs primarily as a result  of insufficient dietary intake or poor absorp-tion. There is widespread global prevalence of vitamin B12 deficiency, resulting in considerable morbidity.

  20. Genetics Home Reference: alpha-1 antitrypsin deficiency

    Science.gov (United States)

    ... particular ethnic groups? Genetic Changes Mutations in the SERPINA1 gene cause alpha-1 antitrypsin deficiency . This gene ... controlled by alpha-1 antitrypsin. Mutations in the SERPINA1 gene can lead to a shortage (deficiency) of ...

  1. Genetics Home Reference: primary carnitine deficiency

    Science.gov (United States)

    ... Review. Citation on PubMed Tein I. Carnitine transport: pathophysiology and metabolism of known molecular defects. J Inherit ... newborn screening? New Pages MDA5 deficiency type 2 diabetes mitochondrial complex I deficiency All New & Updated Pages ...

  2. Neuropathology in Succinic Semialdehyde Dehydrogenase Deficiency

    NARCIS (Netherlands)

    Knerr, I.; Gibson, K.M.; Murdoch, G.; Salomons, G.S.; Jakobs, C.; Combs, S.; Pearl, P.L.

    2010-01-01

    Reported here is the novel finding of neuropathology in a patient with succinic semialdehyde dehydrogenase deficiency, an inherited disorder of γ-aminobutyric acid metabolism characterized by intellectual deficiency, hypotonia, and epilepsy, with 4-hydroxybutyric aciduria and abnormalities of the

  3. Perinatal iron deficiency and neurocognitive development

    National Research Council Canada - National Science Library

    Radlowski, Emily C; Johnson, Rodney W

    2013-01-01

    Iron deficiency is the most common form of nutrient deficiency worldwide. It is highly prevalent due to the limited availability of high quality food in developing countries and poor dietary habits in industrialized countries...

  4. Boron deficiency in woody plants: various responses and tolerance mechanisms

    Directory of Open Access Journals (Sweden)

    Nannan eWang

    2015-10-01

    Full Text Available Boron (B is an essential microelement for higher plants, and its deficiency is widespread around the world and constrains the productivity of both agriculture and forestry. In the last decades, accumulating studies on model or herbaceous plants have contributed greatly to our understanding of the complex network of B-deficiency responses and mechanisms for tolerance. In woody plants, however, only a few studies have been conducted and they are not well synthesised. Trees have a larger body size, longer lifespan and more B reserves than do herbaceous plants, indicating that woody species might undergo long-term or mild B deficiency more commonly and that a more complicated B reserves must accordingly be developed to cope with B deficiency. In addition, the highly heterozygous genetic background of tree species suggests that they may have a more complicated mechanism of response and tolerance to B deficiency than do model plants.B-deficient trees usually exhibit two key visible symptoms: depression of growing points (root tip, bud, flower, and young leaf and deformity of organs (root, shoot, leaf, and fruit. These symptoms may be ascribed to B functioning in the cell wall and membrane, and B deficiency results in damage to vascular tissues and the suppression of both B and water transport. B deficiency also affects metabolic processes, such as increased lignin and phenol, and decreased leaf photosynthesis. These negative effects will influence the quality and quantity of wood, fruit and other agricultural products.B efficiency probably originates from a combined effect of three processes: B uptake, B translocation and retranslocation, and B utilization. Root morphology and mycorrhiza can affect the B uptake efficiency of trees. During B translocation from the root to shoot, differences in B concentration between root cell saps and xylem exudates, as well as water use efficiency, may play key roles in tolerance to B deficiency. In addition, B

  5. Cobalamin deficiency, hyperhomocysteinemia, and dementia

    Directory of Open Access Journals (Sweden)

    Steven F Werder

    2010-04-01

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

  6. Multiple carboxylase deficiency (late onset due to deficiency of biotinidase

    Directory of Open Access Journals (Sweden)

    Debadatta Mukhopadhyay

    2014-01-01

    Full Text Available Biotinidase is a ubiquitous mammalian cell enzyme occurring in liver, serum and kidney. It cleaves biotin from biocytin, which is a cofactor for biotin dependent enzymes, namely the human carboxylases. Biotinidase deficiency is associated with a wide spectrum of neurological, dermatological, immunological and ophthalmological abnormalities. This is a case of a 3-year-old boy presenting with delayed developmental milestones, tachypnea, progressively increasing ataxia, alopecia and dermatitis, all which dramatically responded to high doses of biotin.

  7. EFFICIENCY ON GROUP PROPHYLAXIS OF IODINE DEFICIENCY IN CHILDREN LIVING IN IODINE DEFICIENCY REGION

    Directory of Open Access Journals (Sweden)

    V.R. Kuchma

    2007-01-01

    Full Text Available A complex examination detected that kalium iodide dosage 100 mkg daily promote a rapid normalization of median of ioduria in children aged 8 to 12 years. Even in a case of normal initial level of ioduria iod active at the same dosage doesn't promote an increase of median of ioduria over than optimum level. It wasn't detected any decrease of goiter frequency during 6 months of prophylaxis, while the level of some cognitive indexes (an attention and the frequency of absence from school by the reason of acute respiratory deseases significantly increased. It could be concluded, that iodine prophylaxis using iod active is more effective in mild goiter endemia combine to decrease of attention in prepubertal children. In the case of combination of moderate endemic goiter and normal cognitive function kalium iodide is more preferable in prophylaxis in children.Key words: children, iod deficiency, prophylaxis.

  8. G6PD Deficiency in Turkish Cypriots

    OpenAIRE

    SÖZÜÖZ, Ayşe

    2014-01-01

    1108 Turkish Cypriot men and 318 male labourers from mainland Turkey were screened for G6PD deficiency and haemoglobinopathy traits. The results revealed a 6.7% G6PD deficiency rate in the Turkish Cypriot men and a 1.6% prevalance rate in the Turkish men. The mean haemoglobin level of the G6PD deficient males was approximately 1g/dl lower than that of the non-deficient males.

  9. Genetics Home Reference: familial lipoprotein lipase deficiency

    Science.gov (United States)

    ... Burger-Grutz syndrome endogenous hypertriglyceridaemia familial fat-induced hypertriglyceridemia familial hyperchylomicronemia familial LPL deficiency hyperlipoproteinemia type I hyperlipoproteinemia ...

  10. Iron deficiency and iron deficiency anaemia in women.

    Science.gov (United States)

    Percy, Laura; Mansour, Diana; Fraser, Ian

    2017-04-01

    Iron deficiency (ID) is the most common micronutrient deficiency worldwide with >20% of women experiencing it during their reproductive lives. Hepcidin, a peptide hormone mostly produced by the liver, controls the absorption and regulation of iron. Understanding iron metabolism is pivotal in the successful management of ID and iron deficiency anaemia (IDA) using oral preparations, parenteral iron or blood transfusion. Oral preparations vary in their iron content and can result in gastrointestinal side effects. Parenteral iron is indicated when there are compliance/tolerance issues with oral iron, comorbidities which may affect absorption or ongoing iron losses that exceed absorptive capacity. It may also be the preferred option when rapid iron repletion is required to prevent physiological decompensation or given preoperatively for non-deferrable surgery. As gynaecologists, we focus on managing women's heavy menstrual bleeding (HMB) and assume that primary care clinicians are treating the associated ID/IDA. We now need to take the lead in diagnosing, managing and initiating treatment for ID/IDA and treating HMB simultaneously. This dual management will significantly improve their quality of life. In this chapter we will summarise the importance of iron in cellular functioning, describe how to diagnose ID/IDA and help clinicians choose between the available treatment options. Copyright © 2016. Published by Elsevier Ltd.

  11. Rubidium deficiency in dialysis patients.

    Science.gov (United States)

    Canavese, C; DeCostanzi, E; Branciforte, L; Caropreso, A; Nonnato, A; Pietra, R; Fortaner, S; Jacono, F; Angelini, G; Gallieni, M; Fop, F; Sabbioni, E

    2001-01-01

    Since dialysis has brought long-term survival to uremic patients, we can now speculate on more subtle problems derived from imbalance or sub-optimal regulation of some elements such as trace metals. We focused on the rubidium (Rb) status in dialysis patients (HD), as concerns about its possible deficiency have been raised. Rb in uremic patients was evaluated by: A) serum concentration (graphite furnace atomic absorption spectroscopy) from blood samples of 70 patients on chronic hemodialysis (HD) in comparison with 75 controls; B) tissue concentration (neutron activation analysis) from autopsy or biopsy samples (20) of HD patients in comparison with 21 controls; C) in vivo intradialytic mass balance during standard bicarbonate dialysis in 8 HD patients. A) Serum Rb concentrations in HD patients significantly were lower than in normal controls (304 +/- 81 micrograms/L versus 350 +/- 74 micrograms/L p < 0.001, log-transformed 5.68 +/- 0.28 versus 5.84 +/- 0.20, p < 0.001). Univariate logistic regression analysis found a significantly higher risk of serum Rb < 250-300 and 350 micrograms/L in uremic patients than in controls (Odd ratios or 12.6, 95% CI 2.77-57.04; 4.0, 95% CI 1.92-8.4; 2.08, 95% CI 1.02-4.25, respectively). B) Rb was significantly lower in tissues of HD patients, including brain (2250 +/- 1520 ng/g versus 5490 +/- 1250 ng/g, p = 0.0002) than normal controls. C) Rb was transferred from the patients' blood to the dialysis bath during a standard bicarbonate dialysis session, giving mean intradialytic Rb removal of 4.0 +/- 1.1 mg/session. These results confirm that Rb deficiency may arise in uremic patients, and indicate that diffusive dialysis treatments allow Rb removal which, however, with a standard bicarbonate schedule does not seem to be any greater than that expected with normal urine output (20 mg/week). Further studies are needed to clarify the roles of many factors in this Rb deficiency, including the effects of uremia by itself, pre

  12. alpha-Glucosidase deficiency (Pompe's disease)

    NARCIS (Netherlands)

    Tager, J. M.; Oude Elferink, R. P.; Reuser, A.; Kroos, M.; Ginsel, L. A.; Fransen, J. A.; Klumperman, J.

    1987-01-01

    alpha-Glucosidase is deficient (less than 30% of control) in Pompe's disease, but the extent of the deficiency does not always correlate with the severity of the clinical symptoms. The defects that lead to a deficiency of alpha-glucosidase include synthesis of catalytically inactive protein, absence

  13. Galactose Epimerase Deficiency: Expanding the Phenotype

    NARCIS (Netherlands)

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

    2017-01-01

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

  14. Iron Deficiency in Autism and Asperger Syndrome.

    Science.gov (United States)

    Latif, A.; Heinz, P.; Cook, R.

    2002-01-01

    Retrospective analysis of the full blood count and, when available, serum ferritin measurements of 96 children (52 with autism and 44 with Asperger syndrome) found six autistic children had iron deficiency and 12 of the 23 autistic children with serum ferritin measures were iron deficient. Far fewer Asperger children were iron deficient. Results…

  15. The effect of a dynamic PCL brace on patellofemoral compartment pressures in PCL-and PCL/PLC-deficient knees.

    Science.gov (United States)

    Welch, Tyler; Keller, Thomas; Maldonado, Ruben; Metzger, Melodie; Mohr, Karen; Kvitne, Ronald

    2017-12-01

    The natural history of posterior cruciate ligament (PCL) deficiency includes the development of arthrosis in the patellofemoral joint (PFJ). The purpose of this biomechanical study was to evaluate the hypothesis that dynamic bracing reduces PFJ pressures in PCL- and combined PCL/posterolateral corner (PLC)-deficient knees. Controlled Laboratory Study. Eight fresh frozen cadaveric knees with intact cruciate and collateral ligaments were included. PFJ pressures and force were measured using a pressure mapping system via a lateral arthrotomy at knee flexion angles of 30°, 60°, 90°, and 120° in intact, PCL-deficient, and PCL/PLC-deficient knees under a combined quadriceps/hamstrings load of 400 N/200 N. Testing was then repeated in PCL- and PCL/PLC-deficient knees after application of a dynamic PCL brace. Application of a dynamic PCL brace led to a reduction in peak PFJ pressures in PCL-deficient knees. In addition, the brace led to a significant reduction in peak pressures in PCL/PLC-deficient knees at 60°, 90°, and 120° of flexion. Application of the dynamic brace also led to a reduction in total PFJ force across all flexion angles for both PCL- and PCL/PLC-deficient knees. Dynamic bracing reduces PFJ pressures in PCL- and combined PCL/PLC-deficient knees, particularly at high degrees of knee flexion.

  16. Amputation and rotationplasty in children with limb deficiencies: current concepts.

    Science.gov (United States)

    Sakkers, Ralph; van Wijk, Iris

    2016-12-01

    Amputations and fitting surgery have a long history in children with limb deficiencies. With the current developments in limb reconstruction and new techniques in prosthetics, the indications for amputation and fitting surgery might have shifted, but still have a very important role in creating high functional performance, optimal participation and quality of life. The purpose of this current concepts article is to give an overview of the indications, dilemmas and technical considerations in the decision-making for amputation and fitting surgery. A special part of this overview is dedicated to the indications, variations and outcomes in rotationplasties. The article is based on the experience of a multidisciplinary reconstruction team for children with complex limb deficiencies, as well as research of the literature on the various aspects that cover this multidisciplinary topic. For those children with a more severe limb deficiency, reconstruction is not always feasible for every patient. In those cases, amputation with prosthetic fitting can lead to a good result. Outcomes in quality of life and function do not significantly differ from the children that had reconstruction. For children with a postaxial deficiency with a femur that is too short for lengthening, and with a stable ankle and foot with good function, rotationplasty offers the best functional outcome. However, the decision-making between the different options will depend on different individual factors. Amputations and rotationplasties combined with optimal prosthesis fitting in children with more severe limb deficiencies may lead to excellent short- and long-term results. An experienced multidisciplinary team for children with complex limb deficiencies should guide the patient and parents in the decision-making between the different options without or with prosthesis.

  17. Recommendations for diagnosis and management of metformin-induced vitamin B12 (Cbl) deficiency.

    Science.gov (United States)

    Mazokopakis, Elias E; Starakis, Ioannis K

    2012-09-01

    Metformin treatment is a known pharmacological cause of vitamin B12 (Cbl) deficiency with controversial responsible mechanisms. A possible diagnosis of this deficiency is based mainly on the combination of patient's medical history (usually long-term metformin use), clinical examination (possible neuropsychiatric symptoms and signs), laboratory studies which confirm a Cbl deficiency (haematological abnormalities, low serum Cbl levels, elevated serum total homocysteine and methylmalonic acid levels), and exclusion other causes of Cbl deficiency (as pernicious anaemia, food-cobalamin malabsorption syndrome, other drugs, etc.). In our review, recommendations for diagnosis and management of metformin-induced Cbl deficiency (MICD) in diabetic patients based on medical bibliography are presented and discussed. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  18. Nutritional deficiency in crisphead lettuce grown in hydroponics

    OpenAIRE

    Petrazzini,Lauro L; Souza,Guilherme A; Rodas,Cléber L; Emrich,Eduardo B; Carvalho,Janice G; Souza,Rovilson J

    2014-01-01

    The identification of nutrient deficiency symptoms in lettuce helps both producers and technical staff to keep the plant nutritional balance in their producing areas. The objective of this study was to evaluate production and describe and record the visual symptoms caused by the isolated or combined shortage of K, Ca, B and Zn in crisphead lettuce grown in hydroponics. The experimental design was completely randomized blocks with four replications and eight treatments, representing the single...

  19. Diagnosis of iron deficiency anemia in children of Northeast Brazil

    OpenAIRE

    Carvalho, Antonio Geraldo Cidrão; Lira, Pedro Israel Cabral de; Barros, Maria de Fátima Alcântara; Aléssio, Maria Luiza Martins; Lima, Marília de Carvalho; Carbonneau, Marie Annette; Berger, Jacques; Léger, Claude Louis

    2010-01-01

    OBJECTIVE: To diagnose iron deficiency anemia in children. METHODS: The study was conducted with a sample of 301 children aged six to 30 months attending public daycare centers in the city of Recife, Northeast Brazil, in 2004. The diagnoses of anemia were based on a combination of different hematological and biochemical parameters: hemoglobin, mean corpuscular volume, ferritin, C-reactive protein, transferrin saturation and transferrin receptor. The chi-square test and ANOVA were used in the ...

  20. Mitochondrial deficiency in Cockayne syndrome.

    Science.gov (United States)

    Scheibye-Knudsen, Morten; Croteau, Deborah L; Bohr, Vilhelm A

    2013-01-01

    Cockayne syndrome is a rare inherited disorder characterized by accelerated aging, cachectic dwarfism and many other features. Recent work has implicated mitochondrial dysfunction in the pathogenesis of this disease. This is particularly interesting since mitochondrial deficiencies are believed to be important in the aging process. In this review, we discuss recent findings of mitochondrial pathology in Cockayne syndrome and suggest possible mechanisms for the mitochondrial dysfunction. Published by Elsevier Ireland Ltd.

  1. Mitochondrial deficiency in Cockayne syndrome

    OpenAIRE

    Scheibye-Knudsen, Morten; Croteau, Deborah L.; Bohr, Vilhelm A.

    2013-01-01

    Cockayne syndrome is a rare inherited disorder characterized by accelerated aging, cachectic dwarfism and many other features. Recent work has implicated mitochondrial dysfunction in the pathogenesis of this disease. This is particularly interesting since mitochondrial deficiencies are believed to be important in the aging process. In this review, we will discuss recent findings of mitochondrial pathology in Cockayne syndrome and suggest possible mechanisms for the mitochondrial dysfunction.

  2. Congenital deficiency of factor VII.

    Science.gov (United States)

    Sikka, M; Gomber, S; Madan, N; Rusia, U; Sharma, S

    1996-01-01

    A case of congenital factor VII deficiency in a five-year-old child is reported. The patient, born of a non-consanguineous marriage, presented with repeated bouts of epistaxis since childhood. The prothrombin time (PT) was markedly prolonged with a normal bleeding time (BT), partial thromboplastin time with Kaolin (PTTK) and platelet count. The patient has been on follow up for the last four years and is doing apparently well.

  3. Metabolic surgery and nutritional deficiencies.

    Science.gov (United States)

    Stroh, Christine; Manger, Thomas; Benedix, Frank

    2017-10-01

    The increasing prevalence of morbid obesity in Germany is associated with an increasing number of metabolic surgical interventions. Short-term surgical and long-term metabolic complications such as nutrient deficiencies can be considered as the main risks of metabolic surgery with its malabsorptive but also restrictive procedures. The aim of this review was to characterize the most relevant metabolic complications specific for the various bariatric procedures, which, subsequently, require a permanent surveillance and supplementation, respectively. Furthermore, we aimed to identify if there are diagnostic and therapeutic measures that can prevent those complications. Restrictive bariatric surgery such as "gastric banding" and "sleeve gastrectomy" can be associated with deficiencies related to B-vitamins whereas iron, folate, vitamin B1, B12 and D deficiencies are associated with the malabsorptive procedure such as "biliopancreatic diversion," "duodenal switch" and "Roux-en-Y gastric bypass". Due to possible metabolic and surgical complications after bariatric surgery, patients need to undergo life-long medical and dietetic surveillance. The recently published guidelines of the "American Association of Bariatric and Metabolic Surgery" are the basis for recommendations on supplementation and treatment following weight loss surgery.

  4. Periodontitis associated with plasminogen deficiency: a case report.

    Science.gov (United States)

    Neering, Sarah H; Adyani-Fard, Sabine; Klocke, Astrid; Rüttermann, Stefan; Flemmig, Thomas F; Beikler, Thomas

    2015-05-14

    Plasminogen deficiency is a rare autosomal recessive disease, which is associated with aggressive periodontitis and gingival enlargement. Previously described treatments of plasminogen deficiency associated periodontitis have shown limited success. This is the first case report indicating a successful therapy approach consisting of a non-surgical supra- and subgingival debridement in combination with an adjunctive systemic antibiotic therapy and a strict supportive periodontal regimen over an observation period of 4 years. The intraoral examination of a 17-year-old Turkish female with severe plasminogen deficiency revealed generalized increased pocket probing depths ranging from 6 to 9 mm, bleeding on probing over 30%, generalized tooth mobility, and gingival hyperplasia. Alveolar bone loss ranged from 30% to 50%. Clinical attachment loss corresponded to pocket probing depths. Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Treponema denticola, Prevotella intermedia, Prevotella nigrescens and Eikenella corrodens have been detected by realtime polymerase chain reaction. Periodontal treatment consisted of full mouth disinfection and adjunctive systemic administration of amoxicillin (500 mg tid) and metronidazole (400 mg tid). A strict supportive periodontal therapy regimen every three month in terms of supra- and subgingival debridement was rendered. The reported therapy has significantly improved periodontal health and arrested disease progression. Intraoral examination at the end of the observation period 3.5 years after non-surgical periodontal therapy showed generalized decreased pocket probing depths ranging from 1 to 6 mm, bleeding on probing lower 30%, and tooth mobility class I and II. Furthermore, microbiological analysis shows the absence of Porphyromonas gingivalis, Prevotella intermedia and Treponema denticola after therapy. Adjunctive antibiotic treatment may alter the oral microbiome and thus, the inflammatory response of periodontal

  5. Flu Vaccine Guidance for Patients with Immune Deficiency

    Science.gov (United States)

    ... Guidance for Patients with Immune Deficiency Share | Flu Vaccine Guidance for Patients with Immune Deficiency This article ... should patients with immune deficiency be given the vaccine? Immune deficient patients have a decreased resistance to ...

  6. Combination vaccines

    Directory of Open Access Journals (Sweden)

    David AG Skibinski

    2011-01-01

    Full Text Available The combination of diphtheria, tetanus, and pertussis vaccines into a single product has been central to the protection of the pediatric population over the past 50 years. The addition of inactivated polio, Haemophilus influenzae, and hepatitis B vaccines into the combination has facilitated the introduction of these vaccines into recommended immunization schedules by reducing the number of injections required and has therefore increased immunization compliance. However, the development of these combinations encountered numerous challenges, including the reduced response to Haemophilus influenzae vaccine when given in combination; the need to consolidate the differences in the immunization schedule (hepatitis B; and the need to improve the safety profile of the diphtheria, tetanus, and pertussis combination. Here, we review these challenges and also discuss future prospects for combination vaccines.

  7. Immunoglobulin deficiency in patients with chronic rhinosinusitis: Systematic review of the literature and meta-analysis.

    Science.gov (United States)

    Schwitzguébel, Adrien J-P; Jandus, Peter; Lacroix, Jean-Silvain; Seebach, Jörg D; Harr, Thomas

    2015-12-01

    Several studies have shown a high prevalence of immunoglobulin deficiencies in patients with chronic rhinosinusitis (CRS). We sought to perform a systematic review and meta-analysis to estimate this prevalence more precisely and to identify patients who need substitution treatment. All case series published after 1990 describing patients with CRS, which was defined as symptomatic rhinosinusitis for more than 12 weeks and documented immunoglobulin deficiencies (including deficiencies of IgG with subclasses, IgA, and IgM; specific antibody deficiencies; and potential common variable immunodeficiency), were retrieved. A meta-analysis of the proportion of any combination of common variable immunodeficiency, IgG deficiency, IgA deficiency, and IgM deficiency in patients with CRS was performed by using logit transformation of the prevalence. Recurrent CRS was defined as rhinosinusitis not controlled by appropriate conservative management for 4 months, and difficult-to-treat CRS was defined as noncontrollable rhinosinusitis despite successful sinus surgery and appropriate conservative management for at least 1 year. The meta-analysis revealed a prevalence of pooled IgG, IgA, and IgM deficiencies in 13% of patients with recurrent CRS and 23% of patients with difficult-to-treat CRS. The prevalence of IgG subclass deficiency (5% to 50%) and specific antibody deficiency (8% to 34%) was increased in patients with CRS, as was the prevalence of respiratory allergies in patients with recurrent CRS (31% to 72%). Immunoglobulin deficiency is a frequent condition in patients with CRS. An even higher prevalence of atopy was observed in patients with recurrent CRS. Therefore immunoglobulin titers and accurate allergy diagnostic workups are strongly recommended in these patients to provide specific treatments for symptom alleviation. However, there is a need for larger prospective studies addressing the effect of specific therapeutic interventions for CRS. Copyright © 2015 American

  8. [Distribution iodine deficiency diseases in coastal areas depending on geochemical conditions].

    Science.gov (United States)

    Kiku, P F; Andryukov, B G

    2014-01-01

    In the Primorsky Krai there was performed a population ecological and hygienic analysis of the relationship between the content of chemical elements in the soil and thyroid morbidity in the population of the region. The assessment of the prevalence of iodine deficiency and iodine deficiency diseases was carried out on the basis of the impact of the priority environmental toxic (strontium, nickel, cadmium, lead, arsenic, tin) and essential (nickel, iron, germanium, molybdenum, zinc, selenium) trace elements on the level of iodine deficiency diseases. The level of thyroid pathology in the territory of Primorye was established to be the highest one in areas characterized by the severe iodine deficiency (Northwest geochemical zones), where the structure of thyroid diseases is presented mainly by diffuse nontoxic goiter. Thyroid diseases associated with iodine deficiency in the population of different age groups are the result of multiple and combined imbalance of trace elements, which causes a relative (secondary) iodine deficiency. Thyroid disease in Primorye are environmentally caused diseases of technogenic origin, they are a consequence of the relative iodine deficiency, when on the background of normal iodine supply an imbalance of zinc, iron, cobalt, manganese with excess of such toxic trace elements as lead, strontium, nickel and chromium takes place. Thyroid pathology associated with iodine deficiency, along with other environmentally dependent diseases can be considered as a marker of ecological environment trouble.

  9. Treatment of Anemia of Chronic Disease with True Iron Deficiency in Pregnancy

    Directory of Open Access Journals (Sweden)

    Gabriela Amstad Bencaiova

    2017-01-01

    Full Text Available Objective. We assess and compare the efficacy of anemia treatment in pregnant women with anemia of chronic disease with true iron deficiency and in women with iron deficiency anemia. Study Design. Fifty patients with moderate anemia (hemoglobin 8.0–9.9 g/dl and iron deficiency (ferritin < 15 μg/l were treated in the Anemia Clinic at the Department of Obstetrics. Results. All patients showed stimulation of erythropoiesis as evidenced by an increase in reticulocyte count at day eight of therapy and showed an increase in hemoglobin and hematocrit at the end of therapy (p<0.001. The target hemoglobin (≥10.5 g/dl was achieved in 45/50 women (90%. 12 patients showed anemia of chronic disease with true iron deficiency (12/50; 24%. Seven women (7/12; 59% with anemia of chronic disease and iron deficiency responded well to anemia treatment. 50% of women with anemia of chronic disease and iron deficiency (3/6 responded well to intravenous iron, and 67% (4/6 responded well to the combination of intravenous iron and recombinant human erythropoietin. Conclusion. Because of frequent true iron deficiency in pregnant women with anemia of chronic disease, anemia of chronic disease in pregnancy is often falsely diagnosed as iron deficiency anemia.

  10. Comparative Analysis of the Symbiotic Efficiency of Medicago truncatula and Medicago sativa under Phosphorus Deficiency

    OpenAIRE

    Sulieman, Saad; Schulze, Joachim; Tran, Lam-Son

    2013-01-01

    Phosphorus (P)-deficiency is a major abiotic stress that limits legume growth in many types of soils. The relationship between Medicago and Sinorhizobium, is known to be affected by different environmental conditions. Recent reports have shown that, in combination with S. meliloti 2011, Medicago truncatula had a lower symbiotic efficiency than Medicago sativa. However, little is known about how Medicago–Sinorhizobium is affected by P-deficiency at the whole-plant level. The obj...

  11. The functional localization of cytochromes b in the respiratory chain of anaerobically grown Proteus mirabilis

    NARCIS (Netherlands)

    Van Wielink, J E; Reijnders, W N; Van Spanning, R J; Oltmann, L F; Stouthamer, A.H.

    1986-01-01

    The functional localization of the cytochromes b found in anaerobically grown Proteus mirabilis was investigated. From light absorption spectra, scanned during uninhibited and HQNO-inhibited electron transport to various electron acceptors, it was concluded that all cytochromes b function between

  12. H+ stoichiometry of sites 1 + 2 of the respiratory chain of normal and tumor mitochondria

    Energy Technology Data Exchange (ETDEWEB)

    Villalobo, A.; Alexandre, A.; Lehninger, A.L.

    1984-09-01

    The mechanistic stoichiometry for vectorial H+ ejection coupled to electron transport through energy-conserving segments 1 + 2 was determined on cyanide-inhibited mitochondria from rat liver, rat heart, and Ehrlich ascites tumor cells, and on rat liver mitoplasts with ferricyanide or ferricytochrome c as electron acceptors. K+ (+ valinomycin) and Ca2+ were employed as permeant cations. Three different methods were employed. In the first, known pulses of ferricyanide were added, and the total H+ ejected was determined with a glass electrode. Such measurements gave H+/2e-values exceeding 7.0 for both normal and tumor mitochondria with beta-hydroxybutyrate and other NAD-linked substrates; uptake of Ca2+ was also measured and gave the expected q+/2e-ratios. The second type of measurement was initiated by addition of ferricytochrome c to rat liver mitoplasts, with H+ ejection monitored with the glass electrode and ferricytochrome c reduction by dual-wavelength spectrophotometry; the H+/2e-ratios generally exceeded 7.0. In the third type of measurement, mixing and dilution artifacts were eliminated by oxidizing ferrocytochrome c in situ with a small amount of ferricyanide. H+/2e-ratios for rat liver mitoplasts oxidizing beta-hydroxybutyrate consistently approached or exceeded 7.5. Over 150 measurements made under a variety of conditions gave observed H+/2e-ejection ratios significantly exceeding 7.0, which correlated closely with H+/2e-measurements on sites 1 + 2 + 3, sites 2 + 3, and site 2. Factors leading to the deficit of the observed ratios from the integral value 8 for sites 1 + 2 were discussed.

  13. 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.

  14. DNA Repair Deficiency in Neurodegeneration

    Science.gov (United States)

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

    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 causing Huntington’s disease. Single-strand breaks are common DNA lesions and are associated with the neurodegenerative diseases, ataxia-oculomotor apraxia-1 and spinocerebellar ataxia with axonal neuropathy-1. DNA double-strand breaks are toxic lesions and two main pathways exist for their repair: homologous recombination and non-homologous end-joining. Ataxia telangiectasia and related disorders with defects in these pathways illustrate that such defects can lead to early childhood neurodegeneration. Aging is a risk factor for neurodegeneration and accumulation of oxidative mitochondrial DNA damage may be linked with the age-associated neurodegenerative disorders Alzheimer’s disease, Parkinson’s disease and amyotrophic lateral sclerosis. Mutation in the WRN protein leads to the premature aging disease Werner syndrome, a disorder that features neurodegeneration. In this article we review the evidence linking deficiencies in the DNA repair pathways with neurodegeneration. PMID:21550379

  15. 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...

  16. Organophosphate exposure with pseudocholinesterase deficiency.

    Science.gov (United States)

    Lurati, Ann R

    2013-06-01

    A 36-year-old correctional officer was exposed to lice while at work and self-treated with chlorpyrifos, an organophosphate. The correctional officer applied chlorpyrifos to her entire body and did not wash it off for 8 to 12 hours. Eight hours after the initial application, the correctional officer developed abdominal cramps, diarrhea, sweating, excessive salivation, frequent urination, and increased bronchial secretions. After a phone consultation with the occupational health clinic, the correctional officer reported to the emergency department, was diagnosed with organophosphate toxicity, and was treated with atropine. Later testing revealed that the correctional officer had pseudocholinesterase deficiency. Copyright 2013, SLACK Incorporated.

  17. Red cell glucose 6-phosphate dehydrogenase deficiency in the northern region of Turkey: is G6PD deficiency exclusively a male disease?

    Science.gov (United States)

    Albayrak, Canan; Albayrak, Davut

    2015-03-01

    Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked recessive genetic defect that can cause hemolytic crisis. However, this disease affects both males and females. In Turkey, the frequency of this enzyme deficiency was reported to vary, from 0.25 to 18%, by the geographical area. Its prevalence in the northern Black Sea region of Turkey is unknown. The aims of this study were to assess the prevalence of G6PD deficiency in the northern region Turkey in children and adults with hyperbilirubinemia and hemolytic anemia. This report included a total of 976 G6PD enzyme results that were analyzed between May 2005 and January 2014. G6PD deficiency was detected in 5.0% of all patients. G6PD deficiency was significantly less frequent in females (1.9%, 6/323) than in males (6.6%, 43/653). G6PD deficiency was detected in 3.7% of infants with hyperbilirubinemia, 9.2% of children, and 4.5% of adults with hemolytic anemia. In both the newborn group and the group of children, G6PD deficiency was significantly more frequent in males. In the combined group of children (groups I and II), the proportion of males was 74% and 67% in all groups (P = .0008). In conclusion, in northern region of Turkey, G6PD deficiency is an important cause of neonatal hyperbilirubinemia and hemolytic crisis in children and adults. This study suggests that most pediatricians thought that G6PD deficiency is exclusively a male disease. For this reason, some female patients may have been undiagnosed.

  18. combination Dictionary

    African Journals Online (AJOL)

    rbr

    advanced-level Spanish-speaking EFL learners. 2. Word combinations ... a certain process of segregation as a separate branch of linguistics. While lexi- ... As substantiated by Ilson's investigation of lexicographic practices, most dictionaries ...

  19. Mitochondrial complex I deficiency leads to the retardation of early embryonic development in Ndufs4 knockout mice

    Directory of Open Access Journals (Sweden)

    Mei Wang

    2017-05-01

    Full Text Available Background The NDUFS4 gene encodes an 18-kD subunit of mitochondria complex I, and mutations in this gene lead to the development of a severe neurodegenerative disease called Leigh syndrome (LS in humans. To investigate the disease phenotypes and molecular mechanisms of Leigh syndrome, the Ndufs4 knockout (KO mouse has been widely used as a novel animal model. Because the homozygotes cannot survive beyond child-bearing age, whether Ndufs4 and mitochondrial complex I influence early embryonic development remains unknown. In our study, we attempted to investigate embryonic development in Ndufs4 KO mice, which can be regarded as a Leigh disease model and were created through the CRISPR (clustered regularly interspaced short palindromic repeat and Cas9 (CRISPR associated-mediated genome editing system. Methods We first designed a single guide RNA (sgRNA targeting exon 2 of Ndufs4 to delete the NDUFS4 protein in mouse embryos to mimic Leigh syndrome. Then, we described the phenotypes of our mouse model by forced swimming and the open-field test as well as by assessing other behavioral characteristics. Intracytoplasmic sperm injection (ICSI was performed to obtain KO embryos to test the influence of NDUFS4 deletion on early embryonic development. Results In this study, we first generated Ndufs4 KO mice with physical and behavioral phenotypes similar to Leigh syndrome using the CRISPR/Cas9 system. The low developmental rate of KO embryos that were derived from knockout gametes indicated that the absence of NDUFS4 impaired the development of preimplantation embryos. Discussion In this paper, we first obtained Ndufs4 KO mice that could mimic Leigh syndrome using the CRISPR/Cas9 system. Then, we identified the role of NDUFS4 in early embryonic development, shedding light on its roles in the respiratory chain and fertility. Our model provides a useful tool with which to investigate the function of Ndufs4. Although the pathological mechanisms of the disease

  20. Mitochondrial complex I deficiency leads to the retardation of early embryonic development in Ndufs4 knockout mice.

    Science.gov (United States)

    Wang, Mei; Huang, Ya-Ping; Wu, Han; Song, Ke; Wan, Cong; Chi, A-Ni; Xiao, Ya-Mei; Zhao, Xiao-Yang

    2017-01-01

    The NDUFS4 gene encodes an 18-kD subunit of mitochondria complex I, and mutations in this gene lead to the development of a severe neurodegenerative disease called Leigh syndrome (LS) in humans. To investigate the disease phenotypes and molecular mechanisms of Leigh syndrome, the Ndufs4 knockout (KO) mouse has been widely used as a novel animal model. Because the homozygotes cannot survive beyond child-bearing age, whether Ndufs4 and mitochondrial complex I influence early embryonic development remains unknown. In our study, we attempted to investigate embryonic development in Ndufs4 KO mice, which can be regarded as a Leigh disease model and were created through the CRISPR (clustered regularly interspaced short palindromic repeat) and Cas9 (CRISPR associated)-mediated genome editing system. We first designed a single guide RNA (sgRNA) targeting exon 2 of Ndufs4 to delete the NDUFS4 protein in mouse embryos to mimic Leigh syndrome. Then, we described the phenotypes of our mouse model by forced swimming and the open-field test as well as by assessing other behavioral characteristics. Intracytoplasmic sperm injection (ICSI) was performed to obtain KO embryos to test the influence of NDUFS4 deletion on early embryonic development. In this study, we first generated Ndufs4 KO mice with physical and behavioral phenotypes similar to Leigh syndrome using the CRISPR/Cas9 system. The low developmental rate of KO embryos that were derived from knockout gametes indicated that the absence of NDUFS4 impaired the development of preimplantation embryos. In this paper, we first obtained Ndufs4 KO mice that could mimic Leigh syndrome using the CRISPR/Cas9 system. Then, we identified the role of NDUFS4 in early embryonic development, shedding light on its roles in the respiratory chain and fertility. Our model provides a useful tool with which to investigate the function of Ndufs4. Although the pathological mechanisms of the disease need to be discovered, it helps to understand the

  1. Hematinic deficiencies and anemia statuses in recurrent aphthous stomatitis patients with or without atrophic glossitis.

    Science.gov (United States)

    Wu, Yang-Che; Wu, Yu-Hsueh; Wang, Yi-Ping; Chang, Julia Yu-Fong; Chen, Hsin-Ming; Sun, Andy

    2016-12-01

    Some of recurrent aphthous stomatitis (RAS) patients had concomitant atrophic glossitis (AG). This study assessed whether RAS patients with AG (AG+/RAS patients) or without AG (AG-/RAS patients) had anemia and hematinic deficiencies and to evaluate whether RAS combined with AG or RAS itself was a significant factor causing anemia and hematinic deficiencies in AG+/RAS or AG-/RAS patients, respectively. The mean corpuscular volume (MCV) and mean blood hemoglobin (Hb), iron, vitamin B12, and folic acid levels were measured and compared between any two of three groups of 160 AG+/RAS patients, 195 AG-/RAS patients, and 355 healthy control subjects. Both AG+/RAS and AG-/RAS patients had significantly lower mean Hb, iron, and vitamin B12 levels as well as significantly greater frequencies of Hb, iron, vitamin B12, and folic acid deficiencies than healthy control subjects. Moreover, AG+/RAS patients had significantly lower mean Hb and serum iron level (for women only) and significantly greater frequencies of Hb and iron deficiencies than AG-/RAS patients. Of 69 anemia AG+/RAS patients, 30 (43.5%) had normocytic anemia and 23 (33.3%) had iron deficiency anemia. Of 38 anemia AG-/RAS patients, 26 (68.4%) had normocytic anemia and 5 (13.2%) had iron deficiency anemia. We conclude that some of AG+/RAS or AG-/RAS patients do have anemia and hematinic deficiencies and AG+/RAS patients do have severer anemia statuses and iron deficiency than AG-/RAS patients. RAS combined with AG or RAS itself does play a significant role in causing anemia and hematinic deficiencies in AG+/RAS or AG-/RAS patients, respectively. Copyright © 2016. Published by Elsevier B.V.

  2. 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.

  3. Subacute combined degeneration of the spinal cord in a Nigerian child

    African Journals Online (AJOL)

    Background: Vitamin B12 deficiency has been reported to be associated with a spectrum of neurological disorders among which is subacute combined degeneration of the spinal cord. Method: We report a case of subacute combined degeneration of the spinal cord secondary to vitamin B12 deficiency and discussed the ...

  4. Vitamin B12 deficiency and depression

    OpenAIRE

    Milanlıoğlu, Aysel

    2015-01-01

    Vitamin B12 deficiency may cause psychiatric manifestations preceding the hematological and neurological symptoms. Despite a variety of symptoms, data on the role of vitamin B12 deficiency in depression are sparse. We report a case with B12 deficiency that is diagnosed with psychotic depression and treated successively with vitamin B12 replacement instead of using conventional therapy. Future investigations should focus on the role of vitamin B12 status in depression and other neurops...

  5. Retinal vasculitis revealing immunoglobulin G subclass deficiency.

    Science.gov (United States)

    Hassani, Rachid Tahiri Joutei; Rousseau, Antoine; de Monchy, Ivan; el Sanharawi, Mohamed; Gendron, Gael; Barreau, Emmanuel; Goujard, Cécile; Labetoulle, Marc

    2013-01-01

    Immunoglobulin G (IgG) subclass deficiency is a rare primary immunodeficiency syndrome characterized by recurrent infections and autoimmune disorders. However, there have been no reports of ocular involvement, either inflammatory or infectious, in association with IgG subclass deficiency. The authors report the first case of retinal vasculitis that led to the diagnosis of IgG subclass deficiency, in a patient with a history of inflammatory bowel disease and recurrent infections of previously unknown origin.

  6. Decay-Assisted Laser Spectroscopy of Neutron-Deficient Francium

    CERN Document Server

    Lynch, K M; Bissell, M L; Budincevic, I; Cocolios, T E; De Groote, R P; De Schepper, S; Fedosseev, V N; Flanagan, K T; Franchoo, S; Garcia Ruiz, R F; Heylen, H; Marsh, B A; Neyens, G; Procter, T J; Rossel, R E; Rothe, S; Strashnov, I; Stroke, H H; Wendt, K D A

    2014-01-01

    This paper reports on the hyperfine-structure and radioactive-decay studies of the neutron-deficient francium isotopes $^{202-206}$Fr performed with the Collinear Resonance Ionization Spectroscopy (CRIS) experiment at the ISOLDE facility, CERN. The high resolution innate to collinear laser spectroscopy is combined with the high efficiency of ion detection to provide a highly-sensitive technique to probe the hyperfine structure of exotic isotopes. The technique of decay-assisted laser spectroscopy is presented, whereby the isomeric ion beam is deflected to a decay spectroscopy station for alpha-decay tagging of the hyperfine components. Here, we present the first hyperfine-structure measurements of the neutron-deficient francium isotopes $^{202-206}$Fr, in addition to the identification of the low-lying states of $^{202,204}$Fr performed at the CRIS experiment.

  7. Decay-Assisted Laser Spectroscopy of Neutron-Deficient Francium

    Directory of Open Access Journals (Sweden)

    K. M. Lynch

    2014-03-01

    Full Text Available This paper reports on the hyperfine-structure and radioactive-decay studies of the neutron-deficient francium isotopes ^{202–206}Fr performed with the Collinear Resonance Ionization Spectroscopy (CRIS experiment at the ISOLDE facility, CERN. The high resolution innate to collinear laser spectroscopy is combined with the high efficiency of ion detection to provide a highly sensitive technique to probe the hyperfine structure of exotic isotopes. The technique of decay-assisted laser spectroscopy is presented, whereby the isomeric ion beam is deflected to a decay-spectroscopy station for alpha-decay tagging of the hyperfine components. Here, we present the first hyperfine-structure measurements of the neutron-deficient francium isotopes ^{202–206}Fr, in addition to the identification of the low-lying states of ^{202,204}Fr performed at the CRIS experiment.

  8. Decay-Assisted Laser Spectroscopy of Neutron-Deficient Francium

    Science.gov (United States)

    Lynch, K. M.; Billowes, J.; Bissell, M. L.; Budinčević, I.; Cocolios, T. E.; De Groote, R. P.; De Schepper, S.; Fedosseev, V. N.; Flanagan, K. T.; Franchoo, S.; Garcia Ruiz, R. F.; Heylen, H.; Marsh, B. A.; Neyens, G.; Procter, T. J.; Rossel, R. E.; Rothe, S.; Strashnov, I.; Stroke, H. H.; Wendt, K. D. A.

    2014-01-01

    This paper reports on the hyperfine-structure and radioactive-decay studies of the neutron-deficient francium isotopes Fr202-206 performed with the Collinear Resonance Ionization Spectroscopy (CRIS) experiment at the ISOLDE facility, CERN. The high resolution innate to collinear laser spectroscopy is combined with the high efficiency of ion detection to provide a highly sensitive technique to probe the hyperfine structure of exotic isotopes. The technique of decay-assisted laser spectroscopy is presented, whereby the isomeric ion beam is deflected to a decay-spectroscopy station for alpha-decay tagging of the hyperfine components. Here, we present the first hyperfine-structure measurements of the neutron-deficient francium isotopes Fr202-206, in addition to the identification of the low-lying states of Fr202,204 performed at the CRIS experiment.

  9. Potential of calcium silicate to mitigate water deficiency in maize

    Directory of Open Access Journals (Sweden)

    Douglas José Marques

    2016-01-01

    Full Text Available ABSTRACT The aim of this study was to evaluate the potential of calcium silicate to mitigate the effects of water deficiency in maize plants yield. A completely randomized factorial design, consisting of five combinations of calcium silicate (0, 25, 50, 75, and 100% and five different soil moisture levels (30, 70, 100, 130, and 160%, was adopted. The following parameters were evaluated: soil matric potential, xylem water potential, silicon concentration, leaf dry weight, and dry mass production. Matric potential monitoring confirmed that the irrigation depths employed resulted in different environments for maize plant development during the experiment. Confirming the hypothesis of the study, at the lower irrigation depths, the maize production has accompanied the increase in calcium silicate used as corrective up to the proportion of 50%. These results indicate that silicon mitigated the impact of water deficiency in maize plants and increased the xylem water potential.

  10. Novel Diagnostic Model for the Deficient and Excess Pulse Qualities

    Directory of Open Access Journals (Sweden)

    Jaeuk U. Kim

    2012-01-01

    Full Text Available The deficient and excess pulse qualities (DEPs are the two representatives of the deficiency and excess syndromes, respectively. Despite its importance in the objectification of pulse diagnosis, a reliable classification model for the DEPs has not been reported to date. In this work, we propose a classification method for the DEPs based on a clinical study. First, through factor analysis and Fisher's discriminant analysis, we show that all the pulse amplitudes obtained at various applied pressures at Chon, Gwan, and Cheok contribute on equal orders of magnitude in the determination of the DEPs. Then, we discuss that the pulse pressure or the average pulse amplitude is appropriate for describing the collective behaviors of the pulse amplitudes and a simple and reliable classification can be constructed from either quantity. Finally, we propose an enhanced classification model that combines the two complementary variables sequentially.

  11. Vitamin C deficiency in weanling guinea pigs

    DEFF Research Database (Denmark)

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

    2007-01-01

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

  12. Genetics Home Reference: glutamate formiminotransferase deficiency

    Science.gov (United States)

    ... are some genetic conditions more common in particular ethnic groups? Genetic Changes Mutations in the FTCD gene cause glutamate formiminotransferase deficiency . The FTCD gene provides instructions for ...

  13. Genetics Home Reference: phosphoglycerate mutase deficiency

    Science.gov (United States)

    ... collapse boxes. Description Phosphoglycerate mutase deficiency is a disorder that primarily affects muscles used for movement ( skeletal muscles ). Beginning in childhood or adolescence, affected individuals ...

  14. Complex pregravid preparation for women with deficiency of body weight

    Directory of Open Access Journals (Sweden)

    L. P. Shelestova

    2016-12-01

    Full Text Available Deficiency of a woman's body weight is in direct proportion to the mass of adipose tissue in the body and leads to a significant restructuring of the reproductive function endocrine mechanisms regulation. Aim. To evaluate the effectiveness of the elaborated complex pregravid preparation of women with body weight deficiency. Materials and Methods. We observed 130 women with body weight deficiency, who have visited the antenatal clinic for the purpose of planning pregnancy, 65 of them were treated with the proposed complex of therapeutic and preventive measures, 65 - traditional measures and 35 women with normal body weight. All women were determined by pituitary and ovarian hormones serum content and bone and mineral metabolism indices. The peculiarities of the proposed pregravid preparation are health food (mainly a protein-carbohydrate, daily calorie diet no less then 35 kcal/kg and metabolic correction (prescription of combined cholecalciferol and calcium carbonate drug, which reduces in bone resorption and increases in bone density. Results. It has been noted that hormonal therapy prescription for women with deficiency of body weight, could improve ovarian hormones and prolactin indices, which influenced on menstrual cycle normalization, ovulation induction, and accordingly contributed the pregnancy. The total content of calcium, parathyroid hormone, osteocalcin and vitamin D in women treated with the proposed measures, with the inclusion of calcium carbonate and cholecalciferol, did not differ from women with normal body weight, and whereas women who received traditional therapy, they were reduced significantly. Using the elaborated system promoted a statistically significant reduction in the incidence of spontaneous abortions from 16.3% to 2.0% (P=0.015. Conclusions. Applying elaborated complex of therapeutic and preventive measures for women with low body weight, which additionally to the hormonal status normalization includes health food

  15. The impact of maternal iron deficiency and iron deficiency anemia on child?s health

    OpenAIRE

    Abu-Ouf, Noran M.; Jan, Mohammed M.

    2015-01-01

    Iron deficiency anemia is extremely common, particularly in the developing world, reaching a state of global epidemic. Iron deficiency during pregnancy is one of the leading causes of anemia in infants and young children. Many women go through the entire pregnancy without attaining the minimum required intake of iron. This review aims to determine the impact of maternal iron deficiency and iron deficiency anemia on infants and young children. Extensive literature review revealed that iron def...

  16. 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).

  17. Prevalence and molecular characterization of glucose-6-phosphate dehydrogenase deficiency in northern Thailand.

    Science.gov (United States)

    Charoenkwan, Pimlak; Tantiprabha, Watcharee; Sirichotiyakul, Supatra; Phusua, Arunee; Sanguansermsri, Torpong

    2014-01-01

    Glucose-6-phosphate dehydrogenase (G6PD) deficiency is one of the most common inherited enzymopathies in endemic areas of malaria including Southeast Asia. The molecular features of G6PD deficiency are similar among Southeast Asian population, with differences in the type of the prominent variants in each region. This study determined the prevalence and molecular characteristics of G6PD deficiency in northern Thailand. Quantitative assay of G6PD activity was conducted in 566 neonatal cord blood samples and 6 common G6PD mutations were determined by PCR-restriction fragment length polymorphism method on G6PD complete and intermediate deficiency samples. Ninety newborns had G6PD deficiency, with prevalence in male newborns of 17% and that of female newborns having an intermediate and complete deficiency of 13% and 2%, respectively. From 95 G6PD alleles tested, G6PD Mahidol, G6PD Kaiping, G6PD Canton, G6PD Viangchan, G6PD Union, and G6PD Chinese-5 was detected in 19, 17, 15, 13, 7, and 2 alleles, respectively. Our study shows that the prevalence of G6PD deficiency in northern Thai population is high and combination of the common Chinese mutations is the majority, a distribution different from central and southern Thailand where G6PD Viangchan is the prominent variant. These findings suggest a higher proportion of assimilated Chinese ethnic group in the northern Thai population.

  18. Prevalence and molecular study of G6PD deficiency in Malaysian Orang Asli.

    Science.gov (United States)

    Amini, F; Ismail, E; Zilfalil, B-A

    2011-04-01

    This study aims to define the prevalence and the molecular basis of G6PD deficiency in the Negrito tribe of the Malaysian Orang Asli. Four hundred and eighty seven consenting Negrito volunteers were screened for G6PD deficiency through the use of a fluorescent spot test. DNA from deficient individuals underwent PCR-RFLP analysis using thirteen recognized G6PD mutations. In the instances when the mutation could not be identified by PCR-RFLP, the entire coding region of the G6PD gene was subjected to DNA sequencing. In total, 9% (44/486) of the sample were found to be G6PD-deficient. However, only 25 samples were subjected to PCR-RFLP and DNA sequencing. Of these, three were found to carry Viangchan, one Coimbra and 16, a combination of C1311T in exon 11 and IVS11 T93C. Mutation(s) for the five remaining samples are unknown. The mean G6PD enzyme activity ranged 5.7 IU/gHb in deficient individuals. Our results demonstrate that the frequency of G6PD deficiency is higher among the Negrito Orang Asli than other Malaysian races. The dual presence of C1311T and IVS11 T93C in 64% of the deficient individuals (16/44) could well be a result of genetic drift within this isolated group. © 2011 The Authors. Internal Medicine Journal © 2011 Royal Australasian College of Physicians.

  19. Diagnosis of factor VIII deficiency.

    Science.gov (United States)

    Verbruggen, B; Meijer, P; Novákova, I; Van Heerde, W

    2008-07-01

    The correct diagnosis of factor VIII deficiency and the assessment of severity of the disease are essential for a patient-tailored treatment strategy. An optimal diagnostic procedure comprises sensitive and specific screening methods and factor VIII activity assays. Different screening reagents show variable characteristics and receiver operator characteristic curves are presented showing the relation between sensitivity and specificity of eleven activated partial thromboplastin time reagents. The details of the three methods for factor VIII activity assay, one-stage and two-stage assay and chromogenic assays, are discussed. The chromogenic assay seems to be more sensitive than the one-stage assay with regard to the detection of severe haemophilia. Discrepant results obtained with one-stage and two-stage assays are reviewed and discussed.

  20. Immunoglobulin class-switch recombination deficiencies.

    Science.gov (United States)

    Durandy, Anne; Kracker, Sven

    2012-07-30

    Immunoglobulin class-switch recombination deficiencies (Ig-CSR-Ds) are rare primary immunodeficiencies characterized by defective switched isotype (IgG/IgA/IgE) production. Depending on the molecular defect in question, the Ig-CSR-D may be combined with an impairment in somatic hypermutation (SHM). Some of the mechanisms underlying Ig-CSR and SHM have been described by studying natural mutants in humans. This approach has revealed that T cell-B cell interaction (resulting in CD40-mediated signaling), intrinsic B-cell mechanisms (activation-induced cytidine deaminase-induced DNA damage), and complex DNA repair machineries (including uracil-N-glycosylase and mismatch repair pathways) are all involved in class-switch recombination and SHM. However, several of the mechanisms required for full antibody maturation have yet to be defined. Elucidation of the molecular defects underlying the diverse set of Ig-CSR-Ds is essential for understanding Ig diversification and has prompted better definition of the clinical spectrum of diseases and the development of increasingly accurate diagnostic and therapeutic approaches.