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Sample records for cystathionine beta-synthase deficiency

  1. Homocystinuria due to cystathionine beta synthase deficiency

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    Rao T

    2008-01-01

    Full Text Available A two year-old male child presented with cutis marmorata congenita universalis, brittle hair, mild mental retardation, and finger spasms. Biochemical findings include increased levels of homocysteine in the blood-106.62 µmol/L (normal levels: 5.90-16µmol/L. Biochemical tests such as the silver nitroprusside and nitroprusside tests were positive suggesting homocystinuria. The patient was treated with oral pyridoxine therapy for three months. The child responded well to this therapy and the muscle spasms as well as skin manifestations such as cutis marmorata subsided. The treatment is being continued; the case is reported here because of its rarity. Homocysteinuria arising due to cystathionine beta-synthase (CBS deficiency is an autosomal recessive disorder of methionine metabolism that produces increased levels of urinary homocysteine and methionine It manifests itself in vascular, central nervous system, cutaneous, and connective tissue disturbances and phenotypically resembles Marfan′s syndrome. Skin manifestations include malar flush, thin hair, and cutis reticulata / marmorata.

  2. Cystathionine beta-synthase deficiency causes fat loss in mice.

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    Sapna Gupta

    Full Text Available Cystathionine beta synthase (CBS is the rate-limiting enzyme responsible for the de novo synthesis of cysteine. Patients with CBS deficiency have greatly elevated plasma total homocysteine (tHcy, decreased levels of plasma total cysteine (tCys, and often a marfanoid appearance characterized by thinness and low body-mass index (BMI. Here, we characterize the growth and body mass characteristics of CBS deficient TgI278T Cbs(-/- mice and show that these animals have significantly decreased fat mass and tCys compared to heterozygous sibling mice. The decrease in fat mass is accompanied by a 34% decrease in liver glutathione (GSH along with a significant decrease in liver mRNA and protein for the critical fat biosynthesizing enzyme Stearoyl CoA desaturase-1 (Scd-1. Because plasma tCys has been positively associated with fat mass in humans, we tested the hypothesis that decreased tCys in TgI278T Cbs(-/- mice was the cause of the lean phenotype by placing the animals on water supplemented with N-acetyl cysteine (NAC from birth to 240 days of age. Although NAC treatment in TgI278T Cbs(-/- mice caused significant increase in serum tCys and liver GSH, there was no increase in body fat content or in liver Scd-1 levels. Our results show that lack of CBS activity causes loss of fat mass, and that this effect appears to be independent of low serum tCys.

  3. A revisit to the natural history of homocystinuria due to cystathionine beta-synthase deficiency

    DEFF Research Database (Denmark)

    Skovby, Flemming; Gaustadnes, Mette; Mudd, S Harvey

    2010-01-01

    We review the evidence that in Denmark and probably certain other European countries the number of individuals identified with homocystinuria due to homozygosity for the widespread c.833T>C (p.I278T) mutation in the gene that encodes cystathionine beta-synthase (CBS) falls far short of the number...

  4. Structural basis for substrate activation and regulation by cystathionine beta-synthase (CBS) domains in cystathionine [beta]-synthase

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    Koutmos, Markos; Kabil, Omer; Smith, Janet L.; Banerjee, Ruma (Michigan-Med)

    2011-08-17

    The catalytic potential for H{sub 2}S biogenesis and homocysteine clearance converge at the active site of cystathionine {beta}-synthase (CBS), a pyridoxal phosphate-dependent enzyme. CBS catalyzes {beta}-replacement reactions of either serine or cysteine by homocysteine to give cystathionine and water or H{sub 2}S, respectively. In this study, high-resolution structures of the full-length enzyme from Drosophila in which a carbanion (1.70 {angstrom}) and an aminoacrylate intermediate (1.55 {angstrom}) have been captured are reported. Electrostatic stabilization of the zwitterionic carbanion intermediate is afforded by the close positioning of an active site lysine residue that is initially used for Schiff base formation in the internal aldimine and later as a general base. Additional stabilizing interactions between active site residues and the catalytic intermediates are observed. Furthermore, the structure of the regulatory 'energy-sensing' CBS domains, named after this protein, suggests a mechanism for allosteric activation by S-adenosylmethionine.

  5. Determination of cystathionine beta-synthase activity in human plasma by LC-MS/MS: potential use in diagnosis of CBS deficiency.

    LENUS (Irish Health Repository)

    Krijt, Jakub

    2011-02-01

    Cystathionine β-synthase (CBS) deficiency is usually confirmed by assaying the enzyme activity in cultured skin fibroblasts. We investigated whether CBS is present in human plasma and whether determination of its activity in plasma could be used for diagnostic purposes. We developed an assay to measure CBS activity in 20 μL of plasma using a stable isotope substrate - 2,3,3-(2)H serine. The activity was determined by measurement of the product of enzyme reaction, 3,3-(2)H-cystathionine, using LC-MS\\/MS. The median enzyme activity in control plasma samples was 404 nmol\\/h\\/L (range 66-1,066; n = 57). In pyridoxine nonresponsive CBS deficient patients, the median plasma activity was 0 nmol\\/ho\\/L (range 0-9; n = 26), while in pyridoxine responsive patients the median activity was 16 nmol\\/hour\\/L (range 0-358; n = 28); this overlapped with the enzyme activity from control subject. The presence of CBS in human plasma was confirmed by an in silico search of the proteome database, and was further evidenced by the activation of CBS by S-adenosyl-L-methionine and pyridoxal 5\\'-phosphate, and by configuration of the detected reaction product, 3,3-(2)H-cystathionine, which was in agreement with the previously observed CBS reaction mechanism. We hypothesize that the CBS enzyme in plasma originates from liver cells, as the plasma CBS activities in patients with elevated liver aminotransferase activities were more than 30-fold increased. In this study, we have demonstrated that CBS is present in human plasma and that its catalytic activity is detectable by LC-MS\\/MS. CBS assay in human plasma brings new possibilities in the diagnosis of pyridoxine nonresponsive CBS deficiency.

  6. Determination of cystathionine beta-synthase activity in human plasma by LC-MS/MS: potential use in diagnosis of CBS deficiency.

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    Krijt, Jakub; Kopecká, Jana; Hnízda, Aleš; Moat, Stuart; Kluijtmans, Leo A J; Mayne, Philip; Kožich, Viktor

    2011-02-01

    Cystathionine β-synthase (CBS) deficiency is usually confirmed by assaying the enzyme activity in cultured skin fibroblasts. We investigated whether CBS is present in human plasma and whether determination of its activity in plasma could be used for diagnostic purposes. We developed an assay to measure CBS activity in 20 μL of plasma using a stable isotope substrate - 2,3,3-(2)H serine. The activity was determined by measurement of the product of enzyme reaction, 3,3-(2)H-cystathionine, using LC-MS/MS. The median enzyme activity in control plasma samples was 404 nmol/h/L (range 66-1,066; n = 57). In pyridoxine nonresponsive CBS deficient patients, the median plasma activity was 0 nmol/ho/L (range 0-9; n = 26), while in pyridoxine responsive patients the median activity was 16 nmol/hour/L (range 0-358; n = 28); this overlapped with the enzyme activity from control subject. The presence of CBS in human plasma was confirmed by an in silico search of the proteome database, and was further evidenced by the activation of CBS by S-adenosyl-L-methionine and pyridoxal 5'-phosphate, and by configuration of the detected reaction product, 3,3-(2)H-cystathionine, which was in agreement with the previously observed CBS reaction mechanism. We hypothesize that the CBS enzyme in plasma originates from liver cells, as the plasma CBS activities in patients with elevated liver aminotransferase activities were more than 30-fold increased. In this study, we have demonstrated that CBS is present in human plasma and that its catalytic activity is detectable by LC-MS/MS. CBS assay in human plasma brings new possibilities in the diagnosis of pyridoxine nonresponsive CBS deficiency.

  7. The association of single nucleotide polymorphisms of the maternal cystathionine-beta-synthase gene with early-onset preeclampsia

    NARCIS (Netherlands)

    Holwerda, Kim M.; Weedon-Fekjaer, M. Susanne; Staff, Anne C.; Nolte, Ilja M.; van Goor, Harry; Lely, A. Titia; Faas, Marijke M.

    2016-01-01

    Objectives: Preeclampsia (PE) is a pregnancy complication, characterized by hypertension and proteinuria. The transsulfuration pathway may be involved in its pathophysiology, since homocysteine, cystathionine and cysteine are increased in PE. Cystathionine-beta-synthase (CBS) is a key-enzyme in the

  8. Alterations of Retinal Vasculature in Cystathionine-Beta-Synthase Mutant Mice, a Model of Hyperhomocysteinemia

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    Tawfik, Amany; Al-Shabrawey, Mohamed; Roon, Penny; Sonne, Srinivas; Covar, Jason A.; Matragoon, Surapoon; Ganapathy, Preethi S.; Atherton, Sally S.; El-Remessy, Azza; Ganapathy, Vadivel; Smith, Sylvia B.

    2013-01-01

    Purpose. Mice with moderate/severe hyperhomocysteinemia due to deficiency or absence of the cbs gene encoding cystathionine-beta-synthase (CBS) have marked retinal disruption, ganglion cell loss, optic nerve mitochondrial dysfunction, and ERG defects; those with mild hyperhomocysteinemia have delayed retinal morphological/functional phenotype. Excess homocysteine is a risk factor for cardiovascular diseases; however, it is not known whether excess homocysteine alters retinal vasculature. Methods. Cbs+/+, cbs+/−, and cbs−/− mice (age ∼3 weeks) were subjected to angiography; retinas were harvested for cryosections, flat-mount preparations, or trypsin digestion and subjected to immunofluorescence microscopy to visualize vessels using isolectin-B4, to detect angiogenesis using anti-VEGF and anti-endoglin (anti-CD105) and activated glial cells (anti-glial fibrillary acidic protein [anti-GFAP]) and to investigate the blood–retinal barrier using the tight junction markers zonula occludens-1 (ZO-1) and occludin. Expression of vegf was determined by quantitative RT-PCR (qRT-PCR) and immunoblotting. Human retinal endothelial cells (HRECs) were treated with excess homocysteine to analyze permeability. Results. Angiography revealed vascular leakage in cbs−/− mice; immunohistochemical analysis demonstrated vascular patterns consistent with ischemia; isolectin-B4 labeling revealed a capillary-free zone centrally and new vessels with capillary tufts midperipherally. This was associated with increased vegf mRNA and protein, CD105, and GFAP in cbs−/− retinas concomitant with a marked decrease in ZO-1 and occludin. Homocysteine-treated HRECs showed increased permeability. Conclusions. Severe elevation of homocysteine in cbs−/− mutant mice is accompanied by alterations in retinal vasculature (ischemia, neovascularization, and incompetent blood–retinal barrier). The marked disruption of retinal structure and decreased visual function reported in cbs−/− mice

  9. Engineering of Ion Sensing by the Cystathionine beta-Synthase Module of the ABC Transporter OpuA

    NARCIS (Netherlands)

    Mahmood, Nik A. B. N.; Biemans-Oldehinkel, Esther; Poolman, Bert

    2009-01-01

    We have previously shown that the C-terminal cystathionine beta-synthase (CBS) domains of the nucleotide-binding domains of the ABC transporter OpuA, in conjunction with an anionic membrane surface function, act as sensor of internal ionic strength (I(in)). Here, we show that a surface-exposed catio

  10. Cystathionine beta-synthase (CBS) contributes to advanced ovarian cancer progression and drug resistance.

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    Bhattacharyya, Sanjib; Saha, Sounik; Giri, Karuna; Lanza, Ian R; Nair, K Sreekumar; Jennings, Nicholas B; Rodriguez-Aguayo, Cristian; Lopez-Berestein, Gabriel; Basal, Eati; Weaver, Amy L; Visscher, Daniel W; Cliby, William; Sood, Anil K; Bhattacharya, Resham; Mukherjee, Priyabrata

    2013-01-01

    Epithelial ovarian cancer is the leading cause of gynecologic cancer deaths. Most patients respond initially to platinum-based chemotherapy after surgical debulking, however relapse is very common and ultimately platinum resistance emerges. Understanding the mechanism of tumor growth, metastasis and drug resistant relapse will profoundly impact the therapeutic management of ovarian cancer. Using patient tissue microarray (TMA), in vitro and in vivo studies we report a role of of cystathionine-beta-synthase (CBS), a sulfur metabolism enzyme in ovarian carcinoma. We report here that the expression of cystathionine-beta-synthase (CBS), a sulfur metabolism enzyme, is common in primary serous ovarian carcinoma. The in vitro effects of CBS silencing can be reversed by exogenous supplementation with the GSH and H2S producing chemical Na2S. Silencing CBS in a cisplatin resistant orthotopic model in vivo by nanoliposomal delivery of CBS siRNA inhibits tumor growth, reduces nodule formation and sensitizes ovarian cancer cells to cisplatin. The effects were further corroborated by immunohistochemistry that demonstrates a reduction of H&E, Ki-67 and CD31 positive cells in si-RNA treated as compared to scrambled-RNA treated animals. Furthermore, CBS also regulates bioenergetics of ovarian cancer cells by regulating mitochondrial ROS production, oxygen consumption and ATP generation. This study reports an important role of CBS in promoting ovarian tumor growth and maintaining drug resistant phenotype by controlling cellular redox behavior and regulating mitochondrial bioenergetics. The present investigation highlights CBS as a potential therapeutic target in relapsed and platinum resistant ovarian cancer.

  11. Cystathionine beta-synthase (CBS contributes to advanced ovarian cancer progression and drug resistance.

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    Sanjib Bhattacharyya

    Full Text Available BACKGROUND: Epithelial ovarian cancer is the leading cause of gynecologic cancer deaths. Most patients respond initially to platinum-based chemotherapy after surgical debulking, however relapse is very common and ultimately platinum resistance emerges. Understanding the mechanism of tumor growth, metastasis and drug resistant relapse will profoundly impact the therapeutic management of ovarian cancer. METHODS/PRINCIPAL FINDINGS: Using patient tissue microarray (TMA, in vitro and in vivo studies we report a role of of cystathionine-beta-synthase (CBS, a sulfur metabolism enzyme in ovarian carcinoma. We report here that the expression of cystathionine-beta-synthase (CBS, a sulfur metabolism enzyme, is common in primary serous ovarian carcinoma. The in vitro effects of CBS silencing can be reversed by exogenous supplementation with the GSH and H2S producing chemical Na2S. Silencing CBS in a cisplatin resistant orthotopic model in vivo by nanoliposomal delivery of CBS siRNA inhibits tumor growth, reduces nodule formation and sensitizes ovarian cancer cells to cisplatin. The effects were further corroborated by immunohistochemistry that demonstrates a reduction of H&E, Ki-67 and CD31 positive cells in si-RNA treated as compared to scrambled-RNA treated animals. Furthermore, CBS also regulates bioenergetics of ovarian cancer cells by regulating mitochondrial ROS production, oxygen consumption and ATP generation. This study reports an important role of CBS in promoting ovarian tumor growth and maintaining drug resistant phenotype by controlling cellular redox behavior and regulating mitochondrial bioenergetics. CONCLUSION: The present investigation highlights CBS as a potential therapeutic target in relapsed and platinum resistant ovarian cancer.

  12. Functional modeling of vitamin responsiveness in yeast: a common pyridoxine-responsive cystathionine beta-synthase mutation in homocystinuria.

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    Kim, C E; Gallagher, P M; Guttormsen, A B; Refsum, H; Ueland, P M; Ose, L; Folling, I; Whitehead, A S; Tsai, M Y; Kruger, W D

    1997-12-01

    Cystathionine beta-synthase (CBS) deficiency is an autosomal recessive disorder which results in extremely elevated levels of total plasma homocysteine (tHcy) and high risk of thromboembolic events. About half of all patients diagnosed with CBS deficiency respond to pyridoxine treatment with a significant lowering of tHcy levels. We examined 12 CBS-deficient patients from 10 Norwegian families for mutations in the CBS gene and identified mutations in 18 of the 20 CBS alleles. Five of the seven patients classified as pyridoxine-responsive contain the newly identified point mutation, G797A (R266K). This point mutation is tightly linked with a previously identified 'benign' 68 bp duplication of the intron 7-exon 8 boundary within the CBS gene. We tested the effect of all of the mutations identified on human CBS function utilizing a yeast system. Five of the six mutations had a distinguishable phenotype in yeast, indicating that they were in fact pathogenic. Interestingly, the G797A allele had no phenotype when the yeast were grown in high concentrations of pyridoxine, but a severe phenotype when grown in low concentrations, thus mirroring the behavior in humans. These studies show that the G797A mutation is an important cause of pyridoxine-responsive CBS deficiency and demonstrate the utility of yeast functional assays in the analysis of human mutations.

  13. Relationship Between Polymorphism of Cystathionine beta Synthase Gene and Congenital Heart Disease in Chinese Nuclear Families

    Institute of Scientific and Technical Information of China (English)

    XIAO-MING SONG; XIAO-YING ZHENG; WEN-LI ZHU; LEI HUANG; YONG LI

    2006-01-01

    Objective To study the relationship between polymorphism of cystathionine beta synthase (CBS) gene and development of congenital heart disease (CHD). Methods One hundred and twenty-seven CHD case-parent triads were recruited from Liaoning Province as patient group, and 129 healthy subjects without family history of birth defect were simultaneously recruited as control group together with their biological parents. For all subjects the polymorphism of CBS gene G919A locus was examined by PCR-ARMS method. Results The frequencies of three genotypes (w/w, w/m, and m/m) in control group were 27.2%, 58.4%, and 14.4%, respectively, with no significant difference in gender. A significant difference in the allele frequency was found between CHD patients and controls, the wild allele frequency was 67.9% in patients and 55.7% in controls.CHD parents' genotype distribution was significantly different from that in controls. Further comparison of each type of CHD showed that genotype frequencies in several CHD subtypes were significantly different from those in their corresponding controls. The results of TDT analysis showed that no allele transmission disequilibrium existed in CHD nuclear families.Conclusions CBS gene G919A mutation is associated with the development of CHD, and the mutated allele may decrease the risk of CHD.

  14. Rescue of cystathionine beta-synthase (CBS) mutants with chemical chaperones: purification and characterization of eight CBS mutant enzymes.

    Science.gov (United States)

    Majtan, Tomas; Liu, Lu; Carpenter, John F; Kraus, Jan P

    2010-05-21

    Missense mutations represent the most common cause of many genetic diseases including cystathionine beta-synthase (CBS) deficiency. Many of these mutations result in misfolded proteins, which lack biological function. The presence of chemical chaperones can sometimes alleviate or even restore protein folding and activity of mutant proteins. We present the purification and characterization of eight CBS mutants expressed in the presence of chemical chaperones such as ethanol, dimethyl sulfoxide, or trimethylamine-N-oxide. Preliminary screening in Escherichia coli crude extracts showed that their presence during protein expression had a significant impact on the amount of recovered CBS protein, formation of tetramers, and catalytic activity. Subsequently, we purified eight CBS mutants to homogeneity (P49L, P78R, A114V, R125Q, E176K, P422L, I435T, and S466L). The tetrameric mutant enzymes fully saturated with heme had the same or higher specific activities than wild type CBS. Thermal stability measurements demonstrated that the purified mutants are equally or more thermostable than wild type CBS. The response to S-adenosyl-L-methionine stimulation or thermal activation varied. The lack of response of R125Q and E176K to both stimuli indicated that their specific conformations were unable to reach the activated state. Increased levels of molecular chaperones in crude extracts, particularly DnaJ, indicated a rather indirect effect of the chemical chaperones on folding of CBS mutants. In conclusion, the chemical chaperones present in the expression medium were able to fully restore the activity of eight CBS mutants by improving their protein folding. This finding could have direct implications for the development of a therapeutical approach to pyridoxine unresponsive homocystinuria.

  15. Cystathionine beta-Synthase (CBS) Domains 1 and 2 Fulfill Different Roles in Ionic Strength Sensing of the ATP-binding Cassette (ABC) Transporter OpuA

    NARCIS (Netherlands)

    Karasawa, Akira; Erkens, Guus B.; Berntsson, Ronnie P. -A.; Otten, Renee; Schuurman-Wolters, Gea K.; Mulder, Frans A. A.; Poolman, Bert

    2011-01-01

    The cystathionine beta-synthase module of OpuA in conjunction with an anionic membrane surface acts as a sensor of internal ionic strength, which allows the protein to respond to osmotic stress. We now show by chemical modification and cross-linking studies that CBS2-CBS2 interface residues are crit

  16. Expression of cystathionine beta-synthase and histopathological observations in placentas of patients with Down syndrome.

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    Pinilla, J Martínez; Ayala-Ramírez, P; García-Robles, R; Olaya-C, M; Bermúdez, M

    2015-01-01

    Down syndrome is the most frequent aneuploidy in live births, with an overall frequency of 1/600-700 births. The overexpression of cystathionine β-synthase is thought to participate in the presentation of some phenotypes observed in Down syndrome. The aim of this study was to compare the expression levels of cystathionine β-synthase and histopathological observations from placentas of infants with Down syndrome and healthy newborns. Six placentas of fetuses/infants with Down syndrome and sixteen placentas of healthy fetuses were studied. Cystathionine β-synthase mRNA and protein expression were performed by real-time PCR and immunohistochemistry, respectively. We observed an increase in cystathionine β-synthase mRNA expression (p = 0.0465) and protein levels (p = 0.009) in placentas of fetus/infants with Down syndrome compared with controls. Significantly more circinate edges (p = 0.0007) and trophoblast inclusions (p = 0.0037) were observed in the group with Down syndrome compared with control group. The results demonstrate overexpression of cystathionine β-synthase mRNA and protein in placentas of fetuses/infants with trisomy 21. Further histological abnormalities were found in placentas of patients with Down syndrome, suggesting an alteration in the development of placenta.

  17. Augmented H2S production via cystathionine-beta-synthase upregulation plays a role in pregnancy-associated uterine vasodilation.

    Science.gov (United States)

    Sheibani, Lili; Lechuga, Thomas J; Zhang, Honghai; Hameed, Afshan; Wing, Deborah A; Kumar, Sathish; Rosenfeld, Charles R; Chen, Dong-Bao

    2017-03-01

    Endogenous hydrogen sulfide (H2S) synthesized via metabolizing L-cysteine by cystathionine-beta-synthase (CBS) and cystathionine-gamma-lyase (CSE) is a potent vasodilator and angiogenic factor. The objectives of this study were to determine if human uterine artery (UA) H2S production increases with augmented expression and/or activity of CBS and/or CSE during the menstrual cycle and pregnancy and whether exogenous H2S dilates UA. Uterine arteries from nonpregnant (NP) premenopausal proliferative (pPRM) and secretory (sPRM) phases of the menstrual cycle and pregnant (P) women were studied. H2S production was measured by the methylene blue assay. CBS and CSE mRNAs were assessed by quantitative real-time PCR, and proteins were assessed by immunoblotting and semiquantitative immunofluorescence microscopy. Effects of H2S on rat UA relaxation were determined by wire myography ex vivo. H2S production was greater in NP pPRM and P than NP sPRM UAs and inhibited by the specific CBS but not CSE inhibitor. CBS but not CSE mRNA and protein were greater in NP pPRM and P than NP sPRM UAs. CBS protein was localized to endothelium and smooth muscle and its levels were in a quantitative order of P >NP UAs of pPRM>sPRM. CSE protein was localized in UA endothelium and smooth muscle with no difference among groups. A H2S donor relaxed P > NP UAs but not mesentery artery. Thus, human UA H2S production is augmented with endothelium and smooth muscle CBS upregulation, contributing to UA vasodilation in the estrogen-dominant physiological states in the proliferative phase of the menstrual cycle and pregnancy. © The Authors 2017. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  18. G runs in cystathionine beta-synthase c.833C/c.844_845ins68 mRNA are splicing silencers of pathogenic 3' splice sites.

    Science.gov (United States)

    Romano, Maurizio

    2010-08-01

    The c.844_845ins68 is an evolutionary conserved polymorphism of the cystathionine beta-synthase gene that segregates with the pathogenic c.833C mutation and consists of a 68nt insertion duplicating the 3' splice site between intron 7 and exon 8. The gene rearrangement brought two GGGG runs close to each other and generated a splicing control element that allows the constitutive selection of the more distal 3' splice site in the c.844_854ins68 carriers. In this study, we have characterized functionally the two G4 runs within the duplication and have found that they work as silencers of the upstream potentially pathogenic 3' splice sites has been functionally characterized. This selection allows skipping of both the 68nt-insertion and the c.833C mutation, and is essential to preserve the wild-type ORF. Knocking down hnRNP H and F expression modulated the rescue of the proximal 3' splice site more than hnRNP H alone. These observations suggest that hnRNP H/F contribute jointly to prevention of CBS deficiency in c.844_854ins68 carriers by silencing the potentially pathogenic upstream acceptor site. Copyright © 2010 Elsevier B.V. All rights reserved.

  19. Reduced response of Cystathionine Beta-Synthase (CBS) to S-Adenosylmethionine (SAM): Identification and functional analysis of CBS gene mutations in Homocystinuria patients.

    Science.gov (United States)

    Mendes, Marisa I S; Colaço, Henrique G; Smith, Desirée E C; Ramos, Rúben J J F; Pop, Ana; van Dooren, Silvy J M; Tavares de Almeida, Isabel; Kluijtmans, Leo A J; Janssen, Mirian C H; Rivera, Isabel; Salomons, Gajja S; Leandro, Paula; Blom, Henk J

    2014-03-01

    A reduced response of cystathionine beta-synthase (CBS) to its allosteric activator S-adenosylmethionine (SAM) has been reported to be a cause of CBS dysfunction in homocystinuria patients. In this work we performed a retrospective analysis of fibroblast data from 62 homocystinuria patients and found that 13 of them presented a disturbed SAM activation. Their genotypic background was identified and the corresponding CBS mutant proteins were produced in E. coli. Nine distinct mutations were detected in 22 independent alleles: the novel mutations p.K269del, p.P427L, p.S500L and p.L540Q; and the previously described mutations p.P49L, p.C165Rfs*2, p.I278T, p.R336H and p.D444N. Expression levels and residual enzyme activities, determined in the soluble fraction of E. coli lysates, strongly correlated with the localization of the affected amino acid residue. C-terminal mutations lead to activities in the range of the wild-type CBS and to oligomeric forms migrating faster than tetramers, suggesting an abnormal conformation that might be responsible for the lack of SAM activation. Mutations in the catalytic core were associated with low protein expression levels, decreased enzyme activities and a higher content of high molecular mass forms. Furthermore, the absence of SAM activation found in the patients' fibroblasts was confirmed for all but one of the characterized recombinant proteins (p.P49L). Our study experimentally supports a deficient regulation of CBS by SAM as a frequently found mechanism in CBS deficiency, which should be considered not only as a valuable diagnostic tool but also as a potential target for the development of new therapeutic approaches in classical homocystinuria.

  20. Prevalence of cystathionine beta synthase gene mutation 852Ins68 as a possible risk for neural tube defects in eastern India.

    Science.gov (United States)

    Saxena, A K; Gupta, J; Pandey, S; Gangopadhaya, A N; Pandey, L K

    2011-10-07

    Cystathionine beta synthase gene (CβS) catalyzes the condensation of homocysteine with serine, forming cystathionine by the transsulfuration pathway. Disruption of CβS enzyme activity due to defective folic acid metabolism increases the risk factor for neural tube defects. We evaluated the CβS gene mutation in 25 children with neural tube defects (NTDs), including lumbosacral and thoracic myelomeningocele and open NTDs and mothers of cases, along with 25 healthy children and their mothers, serving as controls. Genomic DNA was isolated to assess the polymorphism of 852Ins68 in the CβS gene using PCR-RFLP analysis and nucleotide sequencing techniques. The 68-bp insertion was observed in one of the 25 NTD cases (lumbosacral myelomeningocele), and in two of the mothers of NTD cases. Statistical analysis was carried out using the Fischer exact probability test, which showed a lack of significance (P > 0.05), but the odds ratio of 2.08 with 95% confidence interval of 0.17-24.6 in NTDs mother was quite high because of the small sample size. However, the study was further extended to find out the involvement of specific nucleotide sequences, which again confirmed the 852Ins68 insertion and replacement of nucleotides (TCCAT to GGGG) in lumbosacral myelomeningocele (due to other category of NTDs), suggesting that it could be an independent risk factor for birth defects, including NTDs.

  1. A missense mutation in the cystathionine {beta}-synthase (CBS) gene associated with pyridoxine (B{sub 6}) responsive homocystinuria

    Energy Technology Data Exchange (ETDEWEB)

    Shih, V.E.; Fringer, J.M.; Mandell, R. [Massachusetts General Hospital, Boston, MA (United States)] [and others

    1994-09-01

    CBS deficiency is an autosomal recessive disorder characterized by homocystinuria and multisystem clinical disease. B{sub 6} responsive patients usually have a milder clinical phenotype than B{sub 6} nonresponsive patients. In our ongoing studies of the molecular defects in CBS deficiency, we reported a T-833 to C transition causing a substitution of threonine for isoleucine at position 278 (I278T). By PCR amplification and sequencing of exon 8 from genomic DNA we have now identified 2 index patients who are homozygous and 5 who are heterozygous for this mutation in a group of 32 patients with CBS deficiency. The mutation was detected in 7 of 10 unrelated families with in vivo B{sub 6} responsiveness, including one with a partial response, and in 0 of 22 B{sub 6} nonresponsive patients. The mutations on the other allele in the compound heterozygotes are still under investigation. We have now observed the I278T mutation in 9 of 20 independent alleles of varied ethnic backgrounds in the subgroup of B{sub 6} responsive patients. These findings, together with the previous report of this mutation in one allele of a B{sub 6} responsive patient, suggest that the I278T mutation is associated with B{sub 6} responsiveness in CBS deficiency. In compound heterozygotes, the degree of B{sub 6} responsiveness may also depend upon the nature of the other mutant allele and/or the interaction between the polypeptide subunits produced by the two mutant allelic genes.

  2. Nitrotyrosinylation, remodeling and endothelial-myocyte uncoupling in iNOS, cystathionine beta synthase (CBS) knockouts and iNOS/CBS double knockout mice.

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    Kundu, Soumi; Kumar, Munish; Sen, Utpal; Mishra, Paras K; Tyagi, Neetu; Metreveli, Naira; Lominadze, David; Rodriguez, Walter; Tyagi, Suresh C

    2009-01-01

    Increased levels of homocysteine (Hcy), recognized as hyperhomocysteinemia (HHcy), were associated with cardiovascular diseases. There was controversy regarding the detrimental versus cardio protective role of inducible nitric oxide synthase (iNOS) in ischemic heart disease. The aim of this study was to test the hypothesis that the Hcy generated nitrotyrosine by inducing the endothelial nitric oxide synthase, causing endothelial-myocyte (E-M) coupling. To differentiate the role of iNOS versus constitutive nitric oxide synthase (eNOS and nNOS) in Hcy-mediated nitrotyrosine generation and matrix remodeling in cardiac dysfunction, left ventricular (LV) tissue was analyzed from cystathionine beta synthase (CBS) heterozygote knockout, iNOS homozygote knockout, CBS-/+/iNOS-/- double knockout, and wild-type (WT) mice. The levels of nitrotyrosine, MMP-2 and -9 (zymographic analysis), and fibrosis (by trichrome stain) were measured. The endothelial-myocyte function was determined in cardiac rings. In CBS-/+ mice, homocysteine was elevated and in iNOS-/- mice, nitric oxide was significantly reduced. The nitrotyrosine and matrix metalloproteinase-9 (MMP-9) levels were elevated in double knockout and CBS-/+ as compared to WT mice. Although MMP-2 levels were similar in CBS-/+, iNOS-/-, and CBS-/+/iNOS-/-, the levels were three- to fourfold higher than WT. The levels of collagen were similar in CBS-/+ and iNOS-/-, but they were threefold higher than WT. Interesting, the levels of collagen increased sixfold in double knockouts, compared to WT, suggesting synergism between high Hcy and lack of iNOS. Left ventricular hypertrophy was exaggerated in the iNOS-/- and double knockout, and mildly increased in the CBS-/+, compared to WT mice. The endothelial-dependent relaxation was attenuated to the same extent in the CBS-/+ and iNOS-/-, compared to WT, but it was robustly blunted in double knockouts. The results concluded that homocysteine generated nitrotyrosine in the vicinity of

  3. Nitrotyrosinylation, Remodeling and Endothelial-Myocyte Uncoupling in iNOS, Cystathionine Beta Synthase (CBS) Knockouts and iNOS/CBS Double Knockout Mice

    Science.gov (United States)

    Kundu, Soumi; Kumar, Munish; Sen, Utpal; Mishra, Paras K.; Tyagi, Neetu; Metreveli, Naira; Lominadze, David; Rodriguez, Walter; Tyagi, Suresh C.

    2009-01-01

    Increased levels of homocysteine (Hcy), recognized as hyperhomocysteinemia (HHcy), were associated with cardiovascular diseases. There was controversy regarding the detrimental versus cardio protective role of inducible nitric oxide synthase (iNOS) in ischemic heart disease. The aim of this study was to test the hypothesis that the Hcy generated nitrotyrosine by inducing the endothelial nitric oxide synthase, causing endothelial-myocyte (E–M) coupling. To differentiate the role of iNOS versus constitutive nitric oxide synthase (eNOS and nNOS) in Hcy-mediated nitrotyrosine generation and matrix remodeling in cardiac dysfunction, left ventricular (LV) tissue was analyzed from cystathionine beta synthase (CBS) heterozygote knockout, iNOS homozygote knockout, CBS−/+/iNOS−/− double knockout, and wild-type (WT) mice. The levels of nitrotyrosine, MMP-2 and -9 (zymographic analysis), and fibrosis (by trichrome stain) were measured. The endothelial-myocyte function was determined in cardiac rings. In CBS−/+ mice, homocysteine was elevated and in iNOS−/− mice, nitric oxide was significantly reduced. The nitrotyrosine and matrix metalloproteinase-9 (MMP-9) levels were elevated in double knockout and CBS−/+ as compared to WT mice. Although MMP-2 levels were similar in CBS−/+, iNOS−/−, and CBS−/+/iNOS−/−, the levels were three- to fourfold higher than WT. The levels of collagen were similar in CBS−/+ and iNOS−/−, but they were threefold higher than WT. Interesting, the levels of collagen increased sixfold in double knockouts, compared to WT, suggesting synergism between high Hcy and lack of iNOS. Left ventricular hypertrophy was exaggerated in the iNOS−/− and double knockout, and mildly increased in the CBS−/+, compared to WT mice. The endothelial-dependent relaxation was attenuated to the same extent in the CBS−/+ and iNOS−/−, compared to WT, but it was robustly blunted in double knockouts. The results concluded that homocysteine

  4. The endogenous hydrogen sulfide producing enzyme cystathionine-beta synthase contributes to visceral hypersensitivity in a rat model of irritable bowel syndrome.

    Science.gov (United States)

    Xu, Guang-Yin; Winston, John H; Shenoy, Mohan; Zhou, Shufang; Chen, Jiande D Z; Pasricha, Pankaj J

    2009-08-06

    The pathogenesis of visceral hypersensitivity, a characteristic pathophysiological feature of irritable bowel syndrome (IBS), remains elusive. Recent studies suggest a role for hydrogen sulfide (H2S) in pain signaling but this has not been well studied in visceral models of hyperalgesia. We therefore determined the role for the endogenous H2S producing enzyme cystathionine-beta-synthetase (CBS) in a validated rat model of IBS-like chronic visceral hyperalgesia (CVH). CVH was induced by colonic injection of 0.5% acetic acid (AA) in 10-day-old rats and experiments were performed at 8-10 weeks of age. Dorsal root ganglion (DRG) neurons innervating the colon were labeled by injection of DiI (1,1'-dioleyl-3,3,3',3-tetramethylindocarbocyanine methanesulfonate) into the colon wall. In rat DRG, CBS-immunoreactivity was observed in approximately 85% of predominantly small- and medium-sized neurons. Colon specific DRG neurons revealed by retrograde labeling DiI were all CBS-positive. CBS-positive colon neurons co-expressed TRPV1 or P2X3 receptors. Western blotting analysis showed that CBS expression was significantly increased in colon DRGs 8 weeks after neonatal AA-treatment. Furthermore, the CBS inhibitor hydroxylamine markedly attenuated the abdominal withdrawal reflex scores in response to colorectal distention in rats with CVH. By contrast, the H2S donor NaHS significantly enhanced the frequency of action potentials of colon specific DRG neurons evoked by 2 times rheobase electrical stimulation. Our results suggest that upregulation of CBS expression in colonic DRG neurons and H2S signaling may play an important role in developing CVH, thus identifying a specific neurobiological target for the treatment of CVH in functional bowel syndromes.

  5. Cystathionine γ-lyase deficiency mediates neurodegeneration in Huntington's disease.

    Science.gov (United States)

    Paul, Bindu D; Sbodio, Juan I; Xu, Risheng; Vandiver, M Scott; Cha, Jiyoung Y; Snowman, Adele M; Snyder, Solomon H

    2014-05-01

    Huntington's disease is an autosomal dominant disease associated with a mutation in the gene encoding huntingtin (Htt) leading to expanded polyglutamine repeats of mutant Htt (mHtt) that elicit oxidative stress, neurotoxicity, and motor and behavioural changes. Huntington's disease is characterized by highly selective and profound damage to the corpus striatum, which regulates motor function. Striatal selectivity of Huntington's disease may reflect the striatally selective small G protein Rhes binding to mHtt and enhancing its neurotoxicity. Specific molecular mechanisms by which mHtt elicits neurodegeneration have been hard to determine. Here we show a major depletion of cystathionine γ-lyase (CSE), the biosynthetic enzyme for cysteine, in Huntington's disease tissues, which may mediate Huntington's disease pathophysiology. The defect occurs at the transcriptional level and seems to reflect influences of mHtt on specificity protein 1, a transcriptional activator for CSE. Consistent with the notion of loss of CSE as a pathogenic mechanism, supplementation with cysteine reverses abnormalities in cultures of Huntington's disease tissues and in intact mouse models of Huntington's disease, suggesting therapeutic potential.

  6. The effect of dietary modulation of sulfur amino acids on cystathionine β synthase-deficient mice.

    Science.gov (United States)

    Kruger, Warren D; Gupta, Sapna

    2016-01-01

    Cystathionine β synthase (CBS) is a key enzyme in the methionine and cysteine metabolic pathway, acting as a metabolic gatekeeper to regulate the flow of fixed sulfur from methionine to cysteine. Mutations in the CBS gene cause clinical CBS deficiency, a disease characterized by elevated plasma total homocysteine (tHcy) and methionine and decreased plasma cysteine. The treatment goal for CBS-deficient patients is to normalize the metabolic values of these three metabolites using a combination of vitamin therapy and dietary manipulation. To better understand the effectiveness of nutritional treatment strategies, we have performed a series of long-term dietary manipulation studies using our previously developed Tg-I278T Cbs(-/-) mouse model of CBS deficiency and sibling Tg-I278T Cbs(+/-) controls. Tg-I278T Cbs(-/-) mice have undetectable levels of CBS activity, extremely elevated plasma tHcy, modestly elevated plasma methionine, and low plasma cysteine. They exhibit several easily assayable phenotypes, including osteoporosis, loss of fat mass, reduced life span, and facial alopecia. The diets used in these studies differed in the amounts of sulfur amino acids or sulfur amino acid precursors. In this review, we will discuss our findings and their relevance to CBS deficiency and the concept of gene-diet interaction. © 2015 New York Academy of Sciences.

  7. Sex-specific dysregulation of cysteine oxidation and the methionine and folate cycles in female cystathionine gamma-lyase null mice: a serendipitous model of the methylfolate trap

    Directory of Open Access Journals (Sweden)

    Hua Jiang

    2015-09-01

    Full Text Available In addition to its role in the endogenous synthesis of cysteine, cystathionine gamma-lyase (CGL is a major physiological source of the vasorelaxant hydrogen sulfide. Cgl null mice are potentially useful for studying the influence of this compound upon vascular tone and endothelial function. Here, we confirm a previous report that female Cgl null mice exhibit an approximate 45-fold increase in plasma total homocysteine compared to wild type controls. This level of homocysteine is approximately 3.5-fold higher than that observed in male Cgl null mice and is essentially equivalent to that observed in mouse models of cystathionine beta synthase deficient homocystinuria. Cgl null mice of both sexes exhibited decreased expression of methylenetetrahydrofolate reductase and cysteinesulfinate decarboxylase compared to WT controls. Female Cgl null mice exhibited a sex-specific induction of betaine homocysteine S-methyltransferase and methionine adenosyltransferase 1, alpha and a 70% decrease in methionine synthase expression accompanied by significantly decreased plasma methionine. Decreased plasma cysteine levels in female Cgl null mice were associated with sex-specific dysregulation of cysteine dioxygenase expression. Comparative histological assessment between cystathionine beta-synthase and Cgl null mice indicated that the therapeutic potential of cystathionine against liver injury merits possible further investigation. Collectively, our data demonstrates the importance of considering sex when investigating mouse models of inborn errors of metabolism and indicate that while female Cgl null mice are of questionable utility for studying the physiological role of hydrogen sulfide, they could serve as a useful model for studying the consequences of methionine synthase deficiency and the methylfolate trap.

  8. Sex-specific dysregulation of cysteine oxidation and the methionine and folate cycles in female cystathionine gamma-lyase null mice: a serendipitous model of the methylfolate trap.

    Science.gov (United States)

    Jiang, Hua; Hurt, K Joseph; Breen, Kelsey; Stabler, Sally P; Allen, Robert H; Orlicky, David J; Maclean, Kenneth N

    2015-08-14

    In addition to its role in the endogenous synthesis of cysteine, cystathionine gamma-lyase (CGL) is a major physiological source of the vasorelaxant hydrogen sulfide. Cgl null mice are potentially useful for studying the influence of this compound upon vascular tone and endothelial function. Here, we confirm a previous report that female Cgl null mice exhibit an approximate 45-fold increase in plasma total homocysteine compared to wild type controls. This level of homocysteine is approximately 3.5-fold higher than that observed in male Cgl null mice and is essentially equivalent to that observed in mouse models of cystathionine beta synthase deficient homocystinuria. Cgl null mice of both sexes exhibited decreased expression of methylenetetrahydrofolate reductase and cysteinesulfinate decarboxylase compared to WT controls. Female Cgl null mice exhibited a sex-specific induction of betaine homocysteine S-methyltransferase and methionine adenosyltransferase 1, alpha and a 70% decrease in methionine synthase expression accompanied by significantly decreased plasma methionine. Decreased plasma cysteine levels in female Cgl null mice were associated with sex-specific dysregulation of cysteine dioxygenase expression. Comparative histological assessment between cystathionine beta-synthase and Cgl null mice indicated that the therapeutic potential of cystathionine against liver injury merits possible further investigation. Collectively, our data demonstrates the importance of considering sex when investigating mouse models of inborn errors of metabolism and indicate that while female Cgl null mice are of questionable utility for studying the physiological role of hydrogen sulfide, they could serve as a useful model for studying the consequences of methionine synthase deficiency and the methylfolate trap.

  9. Vascular complications of cystathionine β-synthase deficiency: future directions for homocysteine-to-hydrogen sulfide research

    OpenAIRE

    Richard S Beard; Bearden, Shawn E.

    2010-01-01

    Homocysteine (Hcy), a cardiovascular and neurovascular disease risk factor, is converted to hydrogen sulfide (H2S) through the transsulfuration pathway. H2S has attracted considerable attention in recent years for many positive effects on vascular health and homeostasis. Cystathionine β-synthase (CBS) is the first, and rate-limiting, enzyme in the transsulfuration pathway. Mutations in the CBS gene decrease enzymatic activity, which increases the plasma Hcy concentration, a condition called h...

  10. Diversity of cystathionine ß-synthase haplotypes bearing the most common homocystinuria mutation c.833T>C: a possible role for gene conversion

    DEFF Research Database (Denmark)

    Vyletal, P; Sokolová, J; Cooper, DN;

    2007-01-01

    Homozygosity or compound heterozygosity for the c.833T>C transition (p.I278 T) in the cystathionine beta-synthase (CBS) gene represents the most common cause of pyridoxine-responsive homocystinuria in Western Eurasians. However, the frequency of the pathogenic c.833C allele, as observed in healthy...

  11. A novel transgenic mouse model of CBS-deficient homocystinuria does not incur hepatic steatosis or fibrosis and exhibits a hypercoagulative phenotype that is ameliorated by betaine treatment.

    Science.gov (United States)

    Maclean, Kenneth N; Sikora, Jakub; Kožich, Viktor; Jiang, Hua; Greiner, Lori S; Kraus, Eva; Krijt, Jakub; Overdier, Katherine H; Collard, Renata; Brodsky, Gary L; Meltesen, Lynne; Crnic, Linda S; Allen, Robert H; Stabler, Sally P; Elleder, Milan; Rozen, Rima; Patterson, David; Kraus, Jan P

    2010-01-01

    Cystathionine beta-synthase (CBS) catalyzes the condensation of homocysteine (Hcy) and serine to cystathionine, which is then hydrolyzed to cysteine by cystathionine gamma-lyase. Inactivation of CBS results in CBS-deficient homocystinuria more commonly referred to as classical homocystinuria, which, if untreated, results in mental retardation, thromboembolic complications, and a range of connective tissue disorders. The molecular mechanisms that underlie the pathology of this disease are poorly understood. We report here the generation of a new mouse model of classical homocystinuria in which the mouse cbs gene is inactivated and that exhibits low-level expression of the human CBS transgene under the control of the human CBS promoter. This mouse model, designated "human only" (HO), exhibits severe elevations in both plasma and tissue levels of Hcy, methionine, S-adenosylmethionine, and S-adenosylhomocysteine and a concomitant decrease in plasma and hepatic levels of cysteine. HO mice exhibit mild hepatopathy but, in contrast to previous models of classical homocystinuria, do not incur hepatic steatosis, fibrosis, or neonatal death with approximately 90% of HO mice living for at least 6months. Tail bleeding determinations indicate that HO mice are in a hypercoagulative state that is significantly ameliorated by betaine treatment in a manner that recapitulates the disease as it occurs in humans. Our findings indicate that this mouse model will be a valuable tool in the study of pathogenesis in classical homocystinuria and the rational design of novel treatments. Copyright © 2010 Elsevier Inc. All rights reserved.

  12. Label-free high-throughput screening via mass spectrometry: a single cystathionine quantitative method for multiple applications.

    Science.gov (United States)

    Holt, Tom G; Choi, Bernard K; Geoghagen, Neil S; Jensen, Kristian K; Luo, Qi; LaMarr, William A; Makara, Gergely M; Malkowitz, Lorraine; Ozbal, Can C; Xiong, Yusheng; Dufresne, Claude; Luo, Ming-Juan

    2009-10-01

    Label-free mass spectrometric (MS) technologies are particularly useful for enzyme assay design for drug discovery screens. MS permits the selective detection of enzyme substrates or products in a wide range of biological matrices without need for derivatization, labeling, or capture technologies. As part of a cardiovascular drug discovery effort aimed at finding modulators of cystathionine beta-synthase (CBS), we used the RapidFire((R)) label-free high-throughput MS (HTMS) technology to develop a high-throughput screening (HTS) assay for CBS activity. The in vitro assay used HTMS to quantify the unlabeled product of the CBS reaction, cystathionine. Cystathionine HTMS analyses were carried out with a throughput of 7 s per sample and quantitation over a linear range of 80-10,000 nM. A compound library of 25,559 samples (or 80 384-well plates) was screened as singlets using the HTMS assay in a period of 8 days. With a hit rate of 0.32%, the actives showed a 90% confirmation rate. The in vitro assay was applied to secondary screens in more complex matrices with no additional analytical development. Our results show that the HTMS method was useful for screening samples containing serum, for cell-based assays, and for liver explants. The novel extension of the in vitro analytical method, without modification, to secondary assays resulted in a significant and advantageous economy of development time for the drug discovery project.

  13. Homocystinuria

    Science.gov (United States)

    ... defects. Alternative Names Cystathionine beta-synthase deficiency; CBS deficiency; HCY Images Pectus excavatum References Rezvani I, Melvin JJ. Defects in metabolism of amino acids. In: Kliegman RM, Stanton BF, St. Geme JW, ...

  14. Betaine supplementation is less effective than methionine restriction in correcting phenotypes of CBS deficient mice.

    Science.gov (United States)

    Gupta, Sapna; Wang, Liqun; Kruger, Warren D

    2016-01-01

    Cystathionine beta synthase (CBS) deficiency is a recessive inborn error of metabolism characterized by elevated serum total homocysteine (tHcy). Betaine supplementation, which can lower tHcy by stimulating homocysteine remethylation to methionine, is often given to CBS deficient patients in combination with other treatments such as methionine restriction and supplemental B-vitamins. However, the effectiveness of betaine supplementation by itself in the treatment of CBS deficiency has not been well explored. Here, we have examined the effect of a betaine supplemented diet on the Tg-I278T Cbs (-/-) mouse model of CBS deficiency and compared its effectiveness to our previously published data using a methionine restricted diet. Tg-I278T Cbs (-/-) mice on betaine, from the time of weaning until for 240 days of age, had a 40 % decrease in mean tHcy level and a 137 % increase in serum methionine levels. Betaine-treated Tg-I278T Cbs (-/-) mice also exhibited increased levels of betaine-dependent homocysteine methyl transferase (BHMT), increased levels of the lipogenic enzyme stearoyl-coenzyme A desaturase (SCD-1), and increased lipid droplet accumulation in the liver. Betaine supplementation largely reversed the hair loss phenotype in Tg-I278T Cbs (-/-) animals, but was far less effective than methionine restriction in reversing the weight-loss, fat-loss, and osteoporosis phenotypes. Surprisingly, betaine supplementation had several negative effects in control Tg-I278T Cbs (+/-) mice including decreased weight gain, lean mass, and bone mineral density. Our findings indicate that while betaine supplementation does have some beneficial effects, it is not as effective as methionine restriction for reversing the phenotypes associated with severe CBS deficiency in mice.

  15. DNA hypomethylation of CBS promoter induced by folate deficiency is a potential noninvasive circulating biomarker for colorectal adenocarcinomas.

    Science.gov (United States)

    Xue, Geng; Lu, Chao-Jing; Pan, Shu-Jun; Zhang, Yin-Ling; Miao, Hui; Shan, Shi; Zhu, Xiao-Ting; Zhang, Yi

    2017-08-01

    Aberrant DNA methylation patterns, which induced by folate deficiency, play important roles in tumorigenesis of colorectal cancer (CRC). Some DNA methylation alterations can also be detected in cell-free DNA (cfDNA) of patients' plasma, making cfDNA an ideal noninvasive circulating biomarker. However, exact DNA methylation alterations induced by folate deficiency in tumorigenesis of CRC and exact potential circulating cfDNA methylation biomarker are still unclear. Therefore, DNA methylation patterns of the normal human colon mucosal epithelial cell line (NCM460), cultured with normal or low folate content, were screened and the DNA hypomethylation of cystathionine-beta-synthase (CBS) promoter was further validated in vitro and vivo. Then, the correlation analysis between folate level, DNA methylation alteration in promoter and expression of CBS was carried out in vitro and vivo. Further, the methylation patterns of CBS promoter in plasma cfDNA were detected and statistically correlated with pathological parameters and clinical outcome. Our study showed that DNA hypomethylation in CBS promoter, induced by folate deficiency, would lead to up-regulation of CBS both in vitro and vivo. Patients with cfDNA hypomethylation of CBS promoter in plasma were correlated with high tumor stage and poor clinical outcome. In addition, cfDNA hypomethylation of CBS promoter in plasma was shown to be an independent prognostic factor for recurrence and cancer-related death in CRC. Our results indicated that DNA hypomethylation of CBS promoter induced by folate deficiency could serve as a potential noninvasive circulating biomarker and may be helpful in developing more effective prognostic markers for CRC.

  16. Gastric acid induces mucosal H2S release in rats by upregulating mRNA and protein expression of cystathionine gamma lyase.

    Science.gov (United States)

    Mard, Seyyed Ali; Veisi, Ali; Ahangarpour, Akram; Gharib-Naseri, Mohammad Kazem

    2015-11-01

    It is well known that hydrogen sulfide (H2S) protects the gastric mucosa against gastric acid and other noxious stimulants by several mechanisms but until now the effect of gastric acid on H2S production has not been evaluated. This study was performed to determine the effect of basal and stimulated gastric acid secretion on mRNA and protein expression of cystathionine gamma lyase (CSE) and cystathionine beta synthase (CBS), and on mucosal release of H2S in rats. Seventy-two male rats were randomly assigned into 9 groups (8 in each)-control, distention, and pentagastrin-induced gastric acid secretion groups. The effects of 15% alcohol solution, propargylglycine (PAG), L-NAME, and pantoprazole were also investigated. Under anesthesia, animals underwent tracheostomy and midline laparotomy. A catheter was inserted into the stomach through the duodenum for gastric washout. At the end of the experiments, the animals were killed and the gastric mucosa was collected to measure H2S concentration and to quantify mRNA expression of CSE and CBS by quantitative real-time PCR, and expression of their proteins by western blot. Basal and stimulated gastric acid secretion increased mucosal levels of H2S, and mRNA and protein expression of CSE. Pantoprazole and L-NAME reversed H2S release and restored protein expression of CSE to the control level. Pantoprazole, but not propargylglycine, pretreatment inhibited the elevated level of protein expression of eNOS in response to distention-induced gastric acid secretion. Our findings indicated that NO mediated the stimulatory effect of gastric acid on H2S release and protein expression of CSE.

  17. 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,...

  18. Selectivity of commonly used pharmacological inhibitors for cystathionine β synthase (CBS) and cystathionine γ lyase (CSE).

    Science.gov (United States)

    Asimakopoulou, Antonia; Panopoulos, Panagiotis; Chasapis, Christos T; Coletta, Ciro; Zhou, Zongmin; Cirino, Giuseppe; Giannis, Athanassios; Szabo, Csaba; Spyroulias, Georgios A; Papapetropoulos, Andreas

    2013-06-01

    Hydrogen sulfide (H₂S) is a signalling molecule that belongs to the gasotransmitter family. Two major sources for endogenous enzymatic production of H₂S are cystathionine β synthase (CBS) and cystathionine γ lyase (CSE). In the present study, we examined the selectivity of commonly used pharmacological inhibitors of H₂S biosynthesis towards CSE and CBS. To address this question, human CSE or CBS enzymes were expressed and purified from Escherichia coli as fusion proteins with GSH-S-transferase. After purification, the activity of the recombinant enzymes was tested using the methylene blue method. β-Cyanoalanine (BCA) was more potent in inhibiting CSE than propargylglycine (PAG) (IC₅₀ 14 ± 0.2 μM vs. 40 ± 8 μM respectively). Similar to PAG, L-aminoethoxyvinylglycine (AVG) only inhibited CSE, but did so at much lower concentrations. On the other hand, aminooxyacetic acid (AOAA), a frequently used CBS inhibitor, was more potent in inhibiting CSE compared with BCA and PAG (IC₅₀ 1.1 ± 0.1 μM); the IC₅₀ for AOAA for inhibiting CBS was 8.5 ± 0.7 μM. In line with our biochemical observations, relaxation to L-cysteine was blocked by AOAA in aortic rings that lacked CBS expression. Trifluoroalanine and hydroxylamine, two compounds that have also been used to block H₂S biosynthesis, blocked the activity of CBS and CSE. Trifluoroalanine had a fourfold lower IC₅₀ for CBS versus CSE, while hydroxylamine was 60-fold more selective against CSE. In conclusion, although PAG, AVG and BCA exhibit selectivity in inhibiting CSE versus CBS, no selective pharmacological CBS inhibitor is currently available. © 2013 The Authors. British Journal of Pharmacology © 2013 The British Pharmacological Society.

  19. Hydrogen sulfide generation in mammals: the molecular biology of cystathionine-β- synthase (CBS) and cystathionine-γ-lyase (CSE).

    Science.gov (United States)

    Renga, Barbara

    2011-04-01

    Cystathionine-β-synthase (CBS) and cystathionine-γ-lyase (CSE) are two key enzymes involved in the synthesis of hydrogen sulphide (H(2)S). CBS catalyzes the pyridoxal 5'-phosphate (PLP)-dependent conversion of homocysteine in Cystathionine whilst CSE the pyridoxal 5'-phosphate (PLP)-dependent synthesis of L-cysteine from Cystathionine. In mammals, CBS gene transcription is poorly investigated and the activity of the enzyme is highly regulated. In fact, the CBS enzyme contains a heme cofactor that functions as a redox sensor and utilizes S-adenosylmethionine (SAM) as an allosteric activator. Impaired CBS activity causes hyperhomocystinuria and hyperhomocysteinemia, both risk factors for cardiovascular diseases. Murine CSE gene regulation is well characterized but little is known about the human counterpart and there is no information regarding the enzyme activity regulation. Recently it has been demonstrated that CSE transcription is regulated by the nuclear receptor Farnesoid X Receptor (FXR). Mutations that decrease the activity of CSE cause cystathioninuria, hypercystathioninemia and increase the risk of developing atherosclerosis and bladder cancer. This review focuses on the recent aspects of the molecular regulation of both CBS and CSE and highlights the possibility that members of the nuclear receptors superfamily might be involved in the regulation of hydrogen sulphide metabolism.

  20. Mapping of DNA Hypermethylation and Hypomethylation induced by Folate Deficiency in Sporadic Colorectal Cancer and Clinical Implication Analysis of Hypermethylation Pattern in CBS Promoter.

    Science.gov (United States)

    Zhang, Zaizhong; He, Yang; Tu, Xiaohuang; Huang, Sheng; Chen, Zhuo; Wang, Lie; Song, Jingxiang

    2017-04-01

    Aberrant DNA methylation patterns play a major role in tumorigenesis and the effects of nutrients, especially folate in the diet, on methylation changes is of great importance in colorectal cancer (CRC). Folate deficiency would disrupt methylation patterns; however, its exact effects on DNA methylation patterns in CRC are unclear. This study was performed to gain insight into the methylation changes induced by folate deficiency and the putative role of methylation pattern diversities of related genes in the clinical outcome of CRC. The NimbleGen MeDIP chip (Methylated DNA Immunoprecipitation chip) assay was used in high-resolution mapping of DNA methylation patterns in the normal human colon mucosal epithelial cell line, NCM460 cultured with or without folate. Aberrant CpG island methylation patterns in the promoter of genes were identified by chip assay and then were confirmed in paired colorectal tissues and corresponding non-malignant tissues obtained from patients by bisulfate sequencing PCR (BSP). Of the total, the expression of cystathionine-beta-synthase (CBS) involved in methyl metabolism and its important substrate, homocysteine, were all detected by realtime RT-PCR and immunostaining. We also analyzed the data of its hypermethylation level statistically correlated with pathological parameters and the clinical outcome in malignant tissues. The chip assay showed that there are 17 genes with hyper or hypomethylation in CpG islands of promoter on chromosome 21, and 8 of them seemed to be associated with tumorigenesis. Among the total, a hypermethylation patterns existed in the promoter of CBS in CRC (p CBS and the accumulation of homocysteine in vitro and vivo (p CBS hypermethylation level is correlated with age (p CBS hypermethylation level significantly correlated with recurrence rate (p = 0.039) and overall survival (p = 0.012) independent of pT stage, pN stage, and liver metastasis. Folate deficiency could induce aberrant DNA methylation patterns and gene

  1. One-carbon cycle alterations induced by Dyrk1a dosage

    Directory of Open Access Journals (Sweden)

    Jean-Maurice Delabar

    2014-01-01

    Full Text Available Hyperhomocysteinemia due to cystathionine beta synthase deficiency confers diverse clinical manifestations. It is characterized by elevated plasma homocysteine levels, a common amino acid metabolized by remethylation to methionine or transsulfuration to cysteine. We recently found a relationship between hepatic Dyrk1A protein expression, a serine/threonine kinase involved in signal transduction in biological processes, hepatic S-adenosylhomocysteine activity, and plasma homocysteine levels. We aimed to study whether there is also a relationship between Dyrk1a and cystathionine beta synthase activity. We used different murine models carrying altered gene coy numbers for Dyrk1a, and found a decreased cystathionine beta synthase activity in the liver of mice under-expressing Dyrk1a, and an increased in liver of mice over-expressing Dyrk1a. For each model, a positive correlation was found between cystathionine beta synthase activity and Dyrk1a protein expression in the liver of mice, which was confirmed in a non-modified genetic context. The positive correlation found between liver Dyrk1a protein expression and CBS activity in modified and non-modified genetic context strengthens the role of this kinase in one carbon metabolism.

  2. Enhanced expression of cystathionine β-synthase and cystathionine γ-lyase during acute cholecystitis-induced gallbladder inflammation.

    Directory of Open Access Journals (Sweden)

    Li Zhang

    Full Text Available BACKGROUND: Hydrogen sulfide (H2S has recently been shown to play an important role in the digestive system, but the role of endogenous H2S produced locally in the gallbladder is unknown. The aim of this study was to investigate whether gallbladder possesses the enzymatic machinery to synthesize H2S, and whether H2S synthesis is changed in gallbladder inflammation during acute acalculous cholecystitis (AC. METHODS: Adult male guinea pigs underwent either a sham operation or common bile duct ligation (CBDL. One, two, or three days after CBDL, the animals were sacrificed separately. Hematoxylin and eosin-stained slides of gallbladder samples were scored for inflammation. H2S production rate in gallbladder tissue from each group was determined; immunohistochemistry and western blotting were used to determine expression levels of the H2S-producing enzymes cystathionine β-synthase (CBS and cystathionine γ-lyase (CSE in gallbladder. RESULTS: There was a progressive inflammatory response after CBDL. Immunohistochemistry analysis showed that CBS and CSE were expressed in the gallbladder epithelium, muscular layer, and blood vessels and that the expression increased progressively with increasing inflammation following CBDL. The expression of CBS protein as well as the H2S-production rate was significantly increased in the animals that underwent CBDL, compared to those that underwent the sham operation. CONCLUSIONS: Both CBS and CSE are expressed in gallbladder tissues. The expression of these enzymes, as well as H2S synthesis, was up-regulated in the context of inflammation during AC.

  3. l-Cystathionine Inhibits the Mitochondria-Mediated Macrophage Apoptosis Induced by Oxidized Low Density Lipoprotein

    Science.gov (United States)

    Zhu, Mingzhu; Du, Junbao; Chen, Siyao; Liu, Angie Dong; Holmberg, Lukas; Chen, Yonghong; Zhang, Chunyu; Tang, Chaoshu; Jin, Hongfang

    2014-01-01

    This study was designed to investigate the regulatory role of l-cystathionine in human macrophage apoptosis induced by oxidized low density lipoprotein (ox-LDL) and its possible mechanisms. THP-1 cells were induced with phorbol 12-myristate 13-acetate (PMA) and differentiated into macrophages. Macrophages were incubated with ox-LDL after pretreatment with l-cystathionine. Superoxide anion, apoptosis, mitochondrial membrane potential, and mitochondrial permeability transition pore (MPTP) opening were examined. Caspase-9 activities and expression of cleaved caspase-3 were measured. The results showed that compared with control group, ox-LDL treatment significantly promoted superoxide anion generation, release of cytochrome c (cytc) from mitochondrion into cytoplasm, caspase-9 activities, cleavage of caspase-3, and cell apoptosis, in addition to reduced mitochondrial membrane potential as well as increased MPTP opening. However, 0.3 and 1.0 mmol/L l-cystathionine significantly reduced superoxide anion generation, increased mitochondrial membrane potential, and markedly decreased MPTP opening in ox-LDL + l-cystathionine macrophages. Moreover, compared to ox-LDL treated-cells, release of cytc from mitochondrion into cytoplasm, caspase-9 activities, cleavage of caspase-3, and apoptosis levels in l-cystathionine pretreated cells were profoundly attenuated. Taken together, our results suggested that l-cystathionine could antagonize mitochondria-mediated human macrophage apoptosis induced by ox-LDL via inhibition of cytc release and caspase activation. PMID:25514411

  4. Human Cystathionine-β-Synthase Phosphorylation on Serine227 Modulates Hydrogen Sulfide Production in Human Urothelium.

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    Roberta d'Emmanuele di Villa Bianca

    Full Text Available Urothelium, the epithelial lining the inner surface of human bladder, plays a key role in bladder physiology and pathology. It responds to chemical, mechanical and thermal stimuli by releasing several factors and mediators. Recently it has been shown that hydrogen sulfide contributes to human bladder homeostasis. Hydrogen sulfide is mainly produced in human bladder by the action of cystathionine-β-synthase. Here, we demonstrate that human cystathionine-β-synthase activity is regulated in a cGMP/PKG-dependent manner through phosphorylation at serine 227. Incubation of human urothelium or T24 cell line with 8-Bromo-cyclic-guanosine monophosphate (8-Br-cGMP but not dibutyryl-cyclic-adenosine monophosphate (d-cAMP causes an increase in hydrogen sulfide production. This result is congruous with the finding that PKG is robustly expressed but PKA only weakly present in human urothelium as well as in T24 cells. The cGMP/PKG-dependent phosphorylation elicited by 8-Br-cGMP is selectively reverted by KT5823, a specific PKG inhibitor. Moreover, the silencing of cystathionine-β-synthase in T24 cells leads to a marked decrease in hydrogen sulfide production either in basal condition or following 8-Br-cGMP challenge. In order to identify the phosphorylation site, recombinant mutant proteins of cystathionine-β-synthase in which Ser32, Ser227 or Ser525 was mutated in Ala were generated. The Ser227Ala mutant cystathionine-β-synthase shows a notable reduction in basal biosynthesis of hydrogen sulfide becoming unresponsive to the 8-Br-cGMP challenge. A specific antibody that recognizes the phosphorylated form of cystathionine-β-synthase has been produced and validated by using T24 cells and human urothelium. In conclusion, human cystathionine-β-synthase can be phosphorylated in a PKG-dependent manner at Ser227 leading to an increased catalytic activity.

  5. Brain phenotype of transgenic mice overexpressing cystathionine β-synthase.

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    Vinciane Régnier

    Full Text Available BACKGROUND: The cystathionine β-synthase (CBS gene, located on human chromosome 21q22.3, is a good candidate for playing a role in the Down Syndrome (DS cognitive profile: it is overexpressed in the brain of individuals with DS, and it encodes a key enzyme of sulfur-containing amino acid (SAA metabolism, a pathway important for several brain physiological processes. METHODOLOGY/PRINCIPAL FINDINGS: Here, we have studied the neural consequences of CBS overexpression in a transgenic mouse line (60.4P102D1 expressing the human CBS gene under the control of its endogenous regulatory regions. These mice displayed a ∼2-fold increase in total CBS proteins in different brain areas and a ∼1.3-fold increase in CBS activity in the cerebellum and the hippocampus. No major disturbance of SAA metabolism was observed, and the transgenic mice showed normal behavior in the rotarod and passive avoidance tests. However, we found that hippocampal synaptic plasticity is facilitated in the 60.4P102D1 line. CONCLUSION/SIGNIFICANCE: We demonstrate that CBS overexpression has functional consequences on hippocampal neuronal networks. These results shed new light on the function of the CBS gene, and raise the interesting possibility that CBS overexpression might have an advantageous effect on some cognitive functions in DS.

  6. Molecular and Functional Analyses of the metC Gene of Lactococcus lactis, Encoding Cystathionine β-Lyase

    NARCIS (Netherlands)

    Fernández, María; Doesburg, Wim van; Rutten, Ger A.M.; Marugg, Joey D.; Alting, Arno C.; Kranenburg, Richard van; Kuipers, Oscar P.

    2000-01-01

    The enzymatic degradation of amino acids in cheese is believed to generate aroma compounds and therefore to be essential for flavor development. Cystathionine β-lyase (CBL) can convert cystathionine to homocysteine but is also able to catalyze an α,γ elimination. With methionine as a substrate, it p

  7. The association of single nucleotide polymorphisms of the maternal cystathionine-β-synthase gene with early-onset preeclampsia

    NARCIS (Netherlands)

    Holwerda, Kim M.; Weedon-Fekjær, M. Susanne; Staff, Anne C.; Nolte, Ilja M.; Van Goor, Harry; Lely, A. Titia; Faas, Marijke M.

    2016-01-01

    Objectives Preeclampsia (PE) is a pregnancy complication, characterized by hypertension and proteinuria. The transsulfuration pathway may be involved in its pathophysiology, since homocysteine, cystathionine and cysteine are increased in PE. Cystathionine-β-synthase (CBS) is a key-enzyme in the path

  8. Recurrent dystonia in homocystinuria: a metabolic pathogenesis.

    Science.gov (United States)

    Sinclair, Alex J; Barling, Lucy; Nightingale, Simon

    2006-10-01

    Dystonia complicating homocystinuria is extremely rare in the absence of thromboembolic disease. We report a unique case of recurrent dystonia in a patient with homocystinuria secondary to pyridoxine-unresponsive cystathionine beta-synthase deficiency. Brain MRI was normal. Two biochemical markers for homocystinuria, homocystine and methionine, were markedly elevated during periods when our patient manifested dystonia. These findings suggest that accumulation of sulfur-containing amino acids may contribute to the pathophysiology of dystonia in patients with homocystinuria.

  9. A critical life-supporting role for cystathionine γ-lyase in the absence of dietary cysteine supply.

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    Mani, Sarathi; Yang, Guangdong; Wang, Rui

    2011-05-15

    This study examined the important relationship between cystathionine γ-lyase (CSE) functionality and cysteine supply for normal growth and life span. Mice with a targeted deletion of the CSE gene (CSE-KO) were fed a cysteine-limited diet and their growth and survival patterns as well as levels of cysteine, homocysteine, glutathione, and hydrogen sulfide (H2S) were measured. CSE-KO mice fed a cysteine-limited diet exhibited growth retardation; decreased levels of cysteine, glutathione, and H2S; and increased plasma homocysteine level. However, histological examinations of liver did not reveal any abnormality and plasma levels of aspartate aminotransferase, alanine aminotransferase, and albumin were normal in these animals. No CSE-KO mice survived after 12 weeks of feeding with the cysteine-limited diet. Supplementation of H2S to the CSE-KO mice failed to reverse the aforementioned abnormalities. On the other hand, supplementation of cysteine in the drinking water of the CSE-KO mice significantly increased plasma cysteine and glutathione levels. This eventually led to an increase in body weight and rescued the animals from death. In conclusion, CSE is critical for cysteine biosynthesis through the transsulfuration pathway and the combination of CSE deficiency and lack of dietary cysteine supply would threaten life sustainability.

  10. Metabolism of amino acids in cats with severe cobalamin deficiency.

    Science.gov (United States)

    Ruaux, C G; Steiner, J M; Williams, D A

    2001-12-01

    To validate an automated chemiluminescent immunoassay for measuring serum cobalamin concentration in cats, to establish and validate gas chromatography-mass spectrometry techniques for use in quantification of methylmalonic acid, homocysteine, cysteine, cystathionine, and methionine in sera from cats, and to investigate serum concentrations of methylmalonic acid, methionine, homocysteine, cystathionine, and cysteine as indicators of biochemical abnormalities accompanying severe cobalamin (vitamin B12) deficiency in cats. Serum samples of 40 cats with severe cobalamin deficiency (serum cobalamin concentration deficiency had significant increases in mean serum concentrations bf methylmalonic acid (9,607 nmol/L), compared with healthy cats (448 nmol/L). Affected cats also had substantial disturbances in amino acid metabolism, compared with healthy cats, with significantly increased serum concentrations of methionine (133.8 vs 101.1 micromol/L) and significantly decreased serum concentrations of cystathionine (449.6 vs 573.2 nmol/L) and cysteine (142.3 vs 163.9 micromol/L). There was not a significant difference in serum concentrations of homocysteine between the 2 groups. Cats with gastrointestinal tract disease may have abnormalities in amino acid metabolism consistent with cobalamin deficiency. Parenteral administration of cobalamin may be necessary to correct these biochemical abnormalities.

  11. Cystathionine β-synthase T833C/844INS68 polymorphism: a family-based study on mentally retarded children

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    Mukhopadhyay Jotideb

    2005-12-01

    Full Text Available Abstract Background Cystathionine β-synthase (CBS mediates conversion of homocysteine to cystathionine and deficiency in enzyme activity may lead to hyperhomocysteinemia/homocystinuria, which are often associated with mental retardation (MR. A large number of polymorphisms have been reported in the CBS gene, some of which impair its activity and among these, a T833C polymorphism in cis with a 68 bp insertion at 844 in the exon 8 is found to be associated with mild hyperhomocysteinemia in different ethnic groups. Methods The present study is aimed at investigating the association between T833C/844ins68 polymorphism and MR. One hundred and ninety MR cases were recruited after psychometric evaluation. Hundred and thirty-eight control subjects, two hundred and sixty-seven parents of MR probands and thirty cardiovascular disorder (CVD patients were included for comparison. Peripheral blood was collected after obtaining informed written consent. The T833C/844ins68 polymorphism was investigated by PCR amplification of genomic DNA and restriction fragment length polymorphism analysis, followed by statistical analysis. Results The genotypic distribution of the polymorphism was within the Hardy-Weinberg equilibrium. A slightly increased genotypic frequency was observed in the Indian control population as compared to other Asian populations. Both haplotype-based haplotype relative risk analysis and transmission disequilibrium test reveled lack of association of the T833C/844ins68 polymorphism with MR; nevertheless, the relative risk calculated was higher (>1 and in a limited number of informative MR families, preferential transmission of the double mutant from heterozygous mothers to the MR probands was noticed (χ2 = 4.00, P Conclusion This is the first molecular genetic study of CBS gene dealing with T833C/844ins68 double mutation in MR subjects. Our preliminary data indicate lack of association between T833C/844ins68 polymorphism with MR. However

  12. 毕氏酵母胱硫醚合成酶基因的克隆和序列分析%PCR Based Cloning and Sequence Analysis of the Pichia pastoris Cystathionine β-Synthase Gene

    Institute of Scientific and Technical Information of China (English)

    李东阳; 吉鑫松; 于健; 陈美娟; 袁中一

    2001-01-01

    The cystathionine β-Synthase (CBS) gene of Pichia pastoris has bee n cloned by homology to the CBS gene of Saccharomyces cerevisiae. First, based on the homology alignment of CBS genes from different sources, a pair of degen erat e PCR primers were designed to amplify a conservative fragment of Pichia pasto ri s CBS gene. After the sequence was revealed, 5′ RACE and 3′ RACE were perfor med separately. The whole sequence of Pichia pasotris CBS gene was assembled. Th is g ene encodes a polypeptide of 501 residues. Comparison of deduced amino acid sequ ence of this new gene with that of S. Cerevisiae CBS showed 54% identity. Di srup tion of CBS gene resulted in a Cys- auxotrophy in Pichia pastoris. The sequence was submitted to GenBank/EMBL/DDBJ under Accession No.AF367364.%胱硫醚合酶(cystathione beta-synthase, CBS)是半胱氨酸代谢中一个重要的酶. 以PCR技术为主, 克隆了毕氏酵母来源的CBS基因. 首先基于不同来源的CBS基因的序列比对, 设计了一对CBS的专一性简并引物, 用它扩增出毕氏酵母CBS基因的一个保守片段. 根据这段DNA的序列, 设计了5′ RACE和3′ RACE的引物, 分别克隆了该基因的3′区和5′区. 由此装配出完整的毕氏酵母的CBS基因序列. 该基因编码了一种501个氨基酸残基的蛋白质. 核苷酸序列和氨基酸序列的排比显示该基因与酿酒酵母来源的CBS基因有较高的相似性. 破坏该基因, 造成毕氏酵母的半胱氨酸生长依赖性. 该序列已存入GenBank/EBM/DDBJ数据库, 其登录号为No. AF367364.

  13. Effect of cysteine on the inactivation of cystathionine gamma-lyase by D,L-propargylglycine.

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    Awata,Shiro

    1989-12-01

    Full Text Available In vivo inactivation of cystathionine gamma-lyase by D,L-propargylglycine, a suicide inhibitor, was found to be less profound in rat kidney than in the liver. We investigated the cause of this difference using rat tissues. We fractionated kidney extract to characterize the substance which protected enzyme, and found that cysteine exhibits protecting action. Addition of 0.3 mM L-cysteine to the incubation mixture containing dialyzed kidney supernatant and 0.5 mM D,L-propargylglycine resulted in the protection of cystathionine gamma-lyase from the inactivation by the inhibitor. The content of cysteine in the kidney was six-fold higher than that in the liver. Thus, we have concluded that one of the reasons why the in vivo inactivation of cystathionine gamma-lyase in rat kidney was less than that in the liver is the presence of a higher concentration of cysteine in the kidney. S-Carboxymethylcysteine, a cysteine derivative, exhibited a similar, but weaker, protective effect.

  14. [Serum cystathionine β-synthase (CBS), cystathionine γ-lyase (CSE ) and cytochrome c oxidase (COX) in copper mine miners potentially expose d to hydrogen sulfide].

    Science.gov (United States)

    Skoczyńska, Anna; Gruszczyński, Leszek; Turczyn, Barbara; Ścieszka, Marek; Wojakowska, Anna; Pawłowski, Tomasz; Schmidt, Edward

    2015-01-01

    The aim of the study was to evaluate serum levels of the target enzyme for H2S toxicity--cytochrome c oxidase (COX) and enzymes involved in the synthesis of H2S--cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE) in copper mine miners. The initial and basic study was conducted respectively in 237 and 88 miners, working in 2 mining shafts: I--no H2S emissions recorded in the last 10 years (study group A) and II--H2S emissions occurred (study group B). A medical examination was performed and 10 ml of blood was collected from miners immediately after exiting the mine. There were no clinical or biochemical changes typical for H2S toxicity. Sulfhemoglobine was undetectable and there were no changes in the red-ox system. However, in group B, regulatory changes were found; a tendency to higher concentration of CBS and CSE, a higher activity of angiotensin converting enzyme (ACE) compared to group A (pCBS and CSE activity. This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.

  15. IMMUNOHISTOCHEMICAL APPROACH REVEALS LOCALIZATION OF CYSTATHIONINE-?-LYASE AND CYSTATHIONINE-ß-SYNTHETASE IN ETHANOL-INDUCED GASTRIC MUCOSA DAMAGE IN MICE

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    Jand-Venes Rolim MEDEIROS

    2013-04-01

    Full Text Available Context Hydrogen sulphide (H2S has been proved to be a neuromodulator and contributes to the maintenance of gastric mucosal integrity in damage caused by anti-inflammatory nonsteroidal drugs. Previously, we demonstrated that H2S synthesis is essential to gastric protection against ethanol. Objective To better understanding the role of H2S and the detailed localization of its production in both normal and injured stomach due to ethanol injection, we studied the expression of cystathionine-γ-lyase (CSE and cystathionine-β-synthetase (CBS isoforms in gastric mucosa of mice treated with saline or 50% ethanol. Methods Mice were treated by gavage with saline or 50% ethanol (0.5 mL/25 g. After 1 hour, mice were sacrificed, and gastric tissue was evaluated by histological and immunohistochemical analysis specific for CSE and CBS. Results We have demonstrated a non-specific expression of CBS in the normal gastric mucosa and expression of CSE occurring mainly in the parietal cells of the animals treated with ethanol. Conclusion Thus, we demonstrated that the expression of CBS appears to be constitutive and diffuse across the gastric epithelium, while the expression of CSE appears to be induced in parietal cells by damage agents such as ethanol.

  16. Anti-atherogenic effect of hydrogen sulfide by over-expression of cystathionine gamma-lyase (CSE gene.

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    Sau Ha Cheung

    Full Text Available Hydrogen sulfide (H2S is an important gaseous signaling molecule that functions in physiological and pathological conditions, such as atherosclerosis. H2S dilates vessels and therefore has been suggested as an anti-atherogenic molecule. Since cystathionine gamma-lyase (CSE enzyme is responsible for producing H2S in the cardiovascular system, we hypothesized that up-regulation of CSE expression in vivo with preservation of H2S bioactivity can slow down plaque formation and, can serve as a therapeutic strategy against atherosclerosis. In this study, C57BL/6 wild type mice (WT, ApoE knockout mice (KO and transgenic ApoE knockout mice overexpressing CSE (Tg/KO at four weeks of age were weaned. They were then fed with either normal or atherogenic diet for 12 weeks. At week 16, serial plasma lipid levels, body weight, and blood pressure were measured prior to euthanization of the mice and the size of atherosclerotic plaques at their aortic roots was measured. Tg/KO mice showed an increase in endogenous H2S production in aortic tissue, reduced atherosclerotic plaque sizes and attenuation in plasma lipid profiles. We also showed an up-regulation in plasma glutathionine peroxidase that could indicate reduced oxidative stress. Furthermore, there was an increase in expression of p-p53 and down regulation of inflammatory nuclear factor-kappa B (NF-κB in aorta. To conclude, alteration of endogenous H2S by CSE gene activation was associated with reduced atherosclerosis in ApoE-deficient mice. Up-regulation of CSE/H2S pathway attenuates atherosclerosis and this would be a potential target for therapeutic intervention against its formation.

  17. Serum cystathionine β-synthase (CBS, cystathionine γ-lyase (CSE and cytochrome c oxidase (COX in copper mine miners potentially expose d to hydrogen sulfide

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    Anna Skoczyńska

    2015-08-01

    Full Text Available Background: The aim of the study was to evaluate serum levels of the target enzyme for H2S toxicity – cytochrome c oxidase (COX and enzymes involved in the synthesis of H2S – cystathionine β-synthase (CBS and cystathionine γ-lyase (CSE in copper mine miners. Material and Methods: The initial and basic study was conducted respectively in 237 and 88 miners, working in 2 mining shafts: I – no H2S emissions recorded in the last 10 years (study group A and II – H2S emissions occurred (study group B. A medical examination was performed and 10 ml of blood was collected from miners immediately after exiting the mine. Results: There were no clinical or biochemical changes typical for H2S toxicity. Sulfhemoglobine was undetectable and there were no changes in the red-ox system. However, in group B, regulatory changes were found; a tendency to higher concentration of CBS and CSE, a higher activity of angiotensin converting enzyme (ACE compared to group A (p < 0.05 and a linear relationship between ACE and CSE (r = 0.6927; p < 0.001. It has been shown that cigarette smoking decreases COX (p < 0.05, however, in miners working in shaft II, the decreased level of COX may result also from the presence of H2S in the gaseous emissions. Conclusions: COX concentration can be a sensitive indicator of exposure to H2S. The measurements of blood H2S concentrations carried out in workplaces should explain the cause of the changes observed in the COX, CBS and CSE activity. Med Pr 2015;66(4:539–548

  18. Exploration of structure-function relationships in Escherichia coli cystathionine γ-synthase and cystathionine β-lyase via chimeric constructs and site-specific substitutions.

    Science.gov (United States)

    Manders, Adrienne L; Jaworski, Allison F; Ahmed, Mohammed; Aitken, Susan M

    2013-06-01

    Cystathionine γ-synthase (CGS) and cystathionine β-lyase (CBL) share a common structure and several active-site residues, but catalyze distinct side-chain rearrangements in the two-step transsulfuration pathway that converts cysteine to homocysteine, the precursor of methionine. A series of 12 chimeric variants of Escherichia coli CGS (eCGS) and CBL (eCBL) was constructed to probe the roles of two structurally distinct, ~25-residue segments situated in proximity to the amino and carboxy termini and located at the entrance of the active-site. In vivo complementation of methionine-auxotrophic E. coli strains, lacking the genes encoding eCGS and eCBL, demonstrated that exchange of the targeted regions impairs the activity of the resulting enzymes, but does not produce a corresponding interchange of reaction specificity. In keeping with the in vivo results, the catalytic efficiency of the native reactions is reduced by at least 95-fold, and α,β versus α,γ-elimination specificity is not modified. The midpoint of thermal denaturation monitored by circular dichroism, ranges between 59 and 80°C, compared to 66°C for the two wild-type enzymes, indicating that the chimeric enzymes adopt a stable folded structure and that the observed reductions in catalytic efficiency are due to reorganization of the active site. Alanine-substitution variants of residues S32 and S33, as well as K42 of eCBL, situated in proximity to and within, respectively, the targeted amino-terminal region were also investigated to explore their role as determinants of reaction specificity via positioning of key active-site residues. The catalytic efficiency of the S32A, S33A and the K42A site-directed variants of eCBL is reduced by less than 10-fold, demonstrating that, while these residues may participate in positioning S339, which tethers the catalytic base, their role is minor.

  19. Expression of cystathionine β-synthase and cystathionine γ-lyase in human pregnant myometrium and their roles in the control of uterine contractility.

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    Xing-Ji You

    Full Text Available BACKGROUND: Human uterus undergoes distinct molecular and functional changes during pregnancy and parturition. Hydrogen sulfide (H(2S has recently been shown to play a key role in the control of smooth muscle tension. The role of endogenous H(2S produced locally in the control of uterine contractility during labour is unknown. METHODOLOGY/PRINCIPAL FINDINGS: Human myometrium biopsies were obtained from pregnant women undergoing cesarean section at term. Immunohistochemistry analysis showed that cystathionine-γ-lyase (CSE and cystathionine-β-synthetase (CBS, the principle enzymes responsible for H(2S generation, were mainly localized to smooth muscle cells of human pregnant myometrium. The mRNA and protein expression of CBS as well as H(2S production rate were down-regulated in labouring tissues compared to nonlabouring tissues. Cumulative administration of L-cysteine (10(-7-10(-2 mol/L, a precursor of H(2S, caused a dose-dependent decrease in the amplitude of spontaneous contractions in nonlabouring and labouring myometrium strips. L-cysteine at high concentration (10(-3 mol/L increased the frequency of spontaneous contractions and induced tonic contraction. These effects of L-cysteine were blocked by the inhibitors of CBS and CSE. Pre-treatment of myometrium strips with glibenclamide, an inhibitor of ATP-sensitive potassium (K(ATP channels, abolished the inhibitory effect of L-cysteine on spontaneous contraction amplitude. The effects of L-cysteine on the amplitude of spontaneous contractions and baseline muscle tone were less potent in labouring tissues than that in nonlabouring strips. CONCLUSION/SIGNIFICANCE: H(2S generated by CSE and CBS locally exerts dual effects on the contractility of pregnant myometrium. Expression of H(2S synthetic enzymes is down-regulated during labour, suggesting that H(2S is one of the factors involved in the transition of pregnant uterus from quiescence to contractile state after onset of parturition.

  20. The H2S-generating enzymes cystathionine β-synthase and cystathionine γ-lyase play a role in vascular development during normal lung alveolarization.

    Science.gov (United States)

    Madurga, Alicia; Golec, Anita; Pozarska, Agnieszka; Ishii, Isao; Mižíková, Ivana; Nardiello, Claudio; Vadász, István; Herold, Susanne; Mayer, Konstantin; Reichenberger, Frank; Fehrenbach, Heinz; Seeger, Werner; Morty, Rory E

    2015-10-01

    The gasotransmitter hydrogen sulfide (H2S) is emerging as a mediator of lung physiology and disease. Recent studies revealed that H2S administration limited perturbations to lung structure in experimental animal models of bronchopulmonary dysplasia (BPD), partially restoring alveolarization, limiting pulmonary hypertension, limiting inflammation, and promoting epithelial repair. No studies have addressed roles for endogenous H2S in lung development. H2S is endogenously generated by cystathionine β-synthase (Cbs) and cystathionine γ-lyase (Cth). We demonstrate here that the expression of Cbs and Cth in mouse lungs is dynamically regulated during lung alveolarization and that alveolarization is blunted in Cbs(-/-) and Cth(-/-) mouse pups, where a 50% reduction in the total number of alveoli was observed, without any impact on septal thickness. Laser-capture microdissection and immunofluorescence staining indicated that Cbs and Cth were expressed in the airway epithelium and lung vessels. Loss of Cbs and Cth led to a 100-500% increase in the muscularization of small- and medium-sized lung vessels, which was accompanied by increased vessel wall thickness, and an apparent decrease in lung vascular supply. Ablation of Cbs expression using small interfering RNA or pharmacological inhibition of Cth using propargylglycine in lung endothelial cells limited angiogenic capacity, causing a 30-40% decrease in tube length and a 50% decrease in number of tubes formed. In contrast, exogenous administration of H2S with GYY4137 promoted endothelial tube formation. These data confirm a key role for the H2S-generating enzymes Cbs and Cth in pulmonary vascular development and homeostasis and in lung alveolarization. Copyright © 2015 the American Physiological Society.

  1. Tyrosol Attenuates High Fat Diet-Induced Hepatic Oxidative Stress: Potential Involvement of Cystathionine β-Synthase and Cystathionine γ-Lyase.

    Science.gov (United States)

    Sarna, Lindsei K; Sid, Victoria; Wang, Pengqi; Siow, Yaw L; House, James D; O, Karmin

    2016-05-01

    The Mediterranean diet is known for its cardioprotective effects. Recently, its protective qualities have also been reported in patients with non-alcoholic fatty liver disease (NAFLD). Oxidative stress is one of the important factors responsible for the development and progression of NAFLD. Hydrogen sulfide (H2S), a multifaceted gasotransmitter, has emerged as a potential therapeutic target in NAFLD. Cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE) are major enzymes responsible for endogenous H2S synthesis. Since oxidative stress contributes to NAFLD pathogenesis, the objective of this study was to investigate the effect of tyrosol, a major compound in olive oil and white wine, on high fat diet-induced hepatic oxidative stress and the mechanisms involved. Mice (C57BL/6) were fed for 5 weeks with a control diet (10 % kcal fat), a high fat diet (60 % kcal fat, HFD) or a HFD supplemented with tyrosol. High fat diet feeding induced hepatic oxidative stress, as indicated by the significant increase in lipid peroxidation and NADPH oxidase activity. Tyrosol supplementation significantly increased hepatic CBS and CSE expression and H2S synthesis in high fat diet-fed mice. Such effects were associated with the attenuation of high fat diet-induced hepatic lipid peroxidation and the restoration of the redox equilibrium of the antioxidant glutathione. Tyrosol also inhibited palmitic acid-induced oxidative stress in hepatocytes (HepG2 cells). These results suggest that the antioxidant properties of tyrosol may be mediated through functional changes in CBS and CSE activity, which might contribute to the hepatoprotective effect of the Mediterranean diet.

  2. Effect of cysteine on the inactivation of cystathionine gamma-lyase by D,L-propargylglycine.

    OpenAIRE

    Awata,Shiro; Nakayama,Kazuko; SUZUKI, Isao; Kodama, Hiroyuki

    1989-01-01

    In vivo inactivation of cystathionine gamma-lyase by D,L-propargylglycine, a suicide inhibitor, was found to be less profound in rat kidney than in the liver. We investigated the cause of this difference using rat tissues. We fractionated kidney extract to characterize the substance which protected enzyme, and found that cysteine exhibits protecting action. Addition of 0.3 mM L-cysteine to the incubation mixture containing dialyzed kidney supernatant and 0.5 mM D,L-propargylglycine resulted i...

  3. Role of the cystathionine γ lyase/hydrogen sulfide pathway in human melanoma progression.

    Science.gov (United States)

    Panza, Elisabetta; De Cicco, Paola; Armogida, Chiara; Scognamiglio, Giosuè; Gigantino, Vincenzo; Botti, Gerardo; Germano, Domenico; Napolitano, Maria; Papapetropoulos, Andreas; Bucci, Mariarosaria; Cirino, Giuseppe; Ianaro, Angela

    2015-01-01

    In humans, two main metabolic enzymes synthesize hydrogen sulfide (H2 S): cystathionine γ lyase (CSE) and cystathionine β synthase (CBS). A third enzyme, 3-mercaptopyruvate sulfurtransferase (3-MST), synthesizes H2 S in the presence of the substrate 3-mercaptopyruvate (3-MP). The immunohistochemistry analysis performed on human melanoma samples demonstrated that CSE expression was highest in primary tumors, decreased in the metastatic lesions and was almost silent in non-lymph node metastases. The primary role played by CSE was confirmed by the finding that the overexpression of CSE induced spontaneous apoptosis of human melanoma cells. The same effect was achieved using different H2 S donors, the most active of which was diallyl trisulfide (DATS). The main pro-apoptotic mechanisms involved were suppression of nuclear factor-κB activity and inhibition of AKT and extracellular signal-regulated kinase pathways. A proof of concept was obtained in vivo using a murine melanoma model. In fact, either l-cysteine, the CSE substrate, or DATS inhibited tumor growth in mice. In conclusion, we have determined that the l-cysteine/CSE/H2 S pathway is involved in melanoma progression.

  4. Novel structural arrangement of nematode cystathionine β-synthases: characterization of Caenorhabditis elegans CBS-1.

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    Vozdek, Roman; Hnízda, Aleš; Krijt, Jakub; Kostrouchová, Marta; Kožich, Viktor

    2012-04-15

    CBSs (cystathionine β-synthases) are eukaryotic PLP (pyridoxal 5 *-phosphate)-dependent proteins that maintain cellular homocysteine homoeostasis and produce cystathionine and hydrogen sulfide. In the present study, we describe a novel structural arrangement of the CBS enzyme encoded by the cbs-1 gene of the nematode Caenorhabditis elegans. The CBS-1 protein contains a unique tandem repeat of two evolutionarily conserved catalytic regions in a single polypeptide chain. These repeats include a catalytically active C-terminal module containing a PLP-binding site and a less conserved N-terminal module that is unable to bind the PLP cofactor and cannot catalyse CBS reactions, as demonstrated by analysis of truncated variants and active-site mutant proteins. In contrast with other metazoan enzymes, CBS-1 lacks the haem and regulatory Bateman domain essential for activation by AdoMet (S-adenosylmethionine) and only forms monomers. We determined the tissue and subcellular distribution of CBS-1 and showed that cbs-1 knockdown by RNA interference leads to delayed development and to an approximately 10-fold elevation of homocysteine concentrations in nematode extracts. The present study provides the first insight into the metabolism of sulfur amino acids and hydrogen sulfide in C. elegans and shows that nematode CBSs possess a structural feature that is unique among CBS proteins.

  5. Molecular and functional analyses of the metC gene of Lactococcus lactis, encoding cystathionine beta-lyase.

    Science.gov (United States)

    Fernández, M; van Doesburg, W; Rutten, G A; Marugg, J D; Alting, A C; van Kranenburg, R; Kuipers, O P

    2000-01-01

    The enzymatic degradation of amino acids in cheese is believed to generate aroma compounds and therefore to be essential for flavor development. Cystathionine beta-lyase (CBL) can convert cystathionine to homocysteine but is also able to catalyze an alpha, gamma elimination. With methionine as a substrate, it produces volatile sulfur compounds which are important for flavor formation in Gouda cheese. The metC gene, which encodes CBL, was cloned from the Lactococcus lactis model strain MG1363 and from strain B78, isolated from a cheese starter culture and known to have a high capacity to produce volatile compounds. The metC gene was found to be cotranscribed with a downstream cysK gene, which encodes a putative cysteine synthase. The MetC proteins of both strains were overproduced in strain MG1363 with the NICE (nisin-controlled expression) system, resulting in a >25-fold increase in cystathionine lyase activity. A disruption of the metC gene was achieved in strain MG1363. Determination of enzymatic activities in the overproducing and knockout strains revealed that MetC is essential for the degradation of cystathionine but that at least one lyase other than CBL contributes to methionine degradation via alpha, gamma elimination to form volatile aroma compounds.

  6. Inhibition of the cystathionine-γ-lyase/hydrogen sulfide pathway in rat vascular smooth muscle cells by cobalt-60 gamma radiation

    Institute of Scientific and Technical Information of China (English)

    ZHONG Guang-zhen; YANG Xin-chun; JIA Li-ping; CHEN Feng-rong; CUI Ming

    2009-01-01

    Background Radiation is a promising treatment for in stent restenosis and restenosis following percutaneous transluminal coronary angioplasty, which has troubled interventional cardiologists for a long time. It inhibits neointima hyperplasia, vascular remodeling, and increases the mean luminal diameter. The mechanism of intracoronary brachytherapy for restenosis is not well understood. Endogenous gaseous transmitters including nitric oxide and carbon monoxide are closely related to restenosis. Hydrogen sulfide, a new endogenous gaseous transmitter, is able to inhibit the proliferation of vascular smooth muscle cells and vascular remodeling. This study aimed to clarify the effect of radiation on cystathionine-y-lyase/hydrogen sulfide pathway in rat smooth muscle cells.Methods We studied the effect of radiation on the cystathionine-γ-lyase/hydrogen sulfide pathway. Rat vascular smooth muscle cells were radiated with 60Co y at doses of 14 Gy and 25 Gy respectively. Then the mRNA level of cystathionine-γ-lyase was studied by quantitative reverse-transcription competitive polymerase chain reaction. Hydrogen sulfide concentration in culture medium was determined by methylene blue spectrophotometry. Cystathionine-γ-lyase activity in vascular smooth muscle cells was also studied.Results 60Co y radiation at a dose of 1 Gy did not affect the cystathionine-γ-lyase/hydrogen sulfide pathway significantly. However, 60Co y radiation at doses of 14 Gy and 25 Gy decreased the hydrogen sulfide synthesis by 21.9% (P <0.05) and 26.8% (P <0.01 ) respectively. At the same time, they decreased the cystathionine-γ-lyase activity by 15.1% (P <0.05) and 20.5% (P <0.01) respectively, and cystathionine-γ-lyase mRNA expression by 29.3% (P <0.01 ) and 38.2% (P <0.01) respectively.Conclusion Appropriate 60Co γ radiation inhibits the H2S synthesis by inhibiting the gene expression of cystathionine-γ-lyase and the cystathionine-y-lyase activity.

  7. Analysis of the sulfur-regulated control of the cystathionine γ-lyase gene of Neurospora crassa

    Directory of Open Access Journals (Sweden)

    Reveal Brad S

    2012-07-01

    Full Text Available Abstract Background Cystathionine γ-lyase plays a key role in the transsulfuration pathway through its primary reaction of catalyzing the formation of cysteine from cystathionine. The Neurospora crassa cystathionine γ-lyase gene (cys-16+ is of particular interest in dissecting the regulation and dynamics of transsulfuration. The aim of this study was to determine the regulatory connection of cys-16+ to the Neurospora sulfur regulatory network. In addition, the cys-16+ promoter was characterized with the goal of developing a strongly expressed and regulatable gene expression tool. Findings The cystathionine γ-lyase cys-16+ gene was cloned and characterized. The gene, which contains no introns, encodes a protein of 417 amino acids with conserved pyridoxal 5’-phosphate binding site and substrate-cofactor binding pocket. Northern blot analysis using wild type cells showed that cys-16+ transcript levels increased under sulfur limiting (derepressing conditions and were present only at a low level under sulfur sufficient (repressing conditions. In contrast, cys-16+ transcript levels in a Δcys-3 regulatory mutant were present at a low level under either derepressing or repressing conditions. Gel mobility shift analysis demonstrated the presence of four CYS3 transcriptional activator binding sites on the cys-16+ promoter, which were close matches to the CYS3 consensus binding sequence. Conclusions In this work, we confirm the control of cystathionine γ-lyase gene expression by the CYS3 transcriptional activator through the loss of cys-16+ expression in a Δcys-3 mutant and through the in vitro binding of CYS3 to the cys-16+ promoter at four sites. The highly regulated cys-16+ promoter should be a useful tool for gene expression studies in Neurospora

  8. Isolation of the patC gene encoding the cystathionine beta-lyase of Lactobacillus delbrueckii subsp. bulgaricus and molecular analysis of inter-strain variability in enzyme biosynthesis.

    Science.gov (United States)

    Aubel, Dominique; Germond, Jacques Edouard; Gilbert, Christophe; Atlan, Danièle

    2002-07-01

    The patC gene encoding the cystathionine beta-lyase (CBL) of Lactobacillus delbrueckii subsp. bulgaricus NCDO 1489 was cloned and expressed in Escherichia coli. Overexpression of CBL complemented the methionine auxotrophy of an E. coli metC mutant, demonstrating in vivo that this enzyme functions as a CBL. However, PatC is distinguishable from the MetC CBLs by a low identity in amino acid sequence, a sensitivity to iodoacetic acid, greater thermostability and a lower substrate affinity. Homologues of patC were detected in the 13 Lb. delbrueckii strains studied, but only seven of them showed CBL activity. In constrast to CBL(+) strains, all CBL-deficient strains analysed were auxotrophic for methionine. This supports the hypothesis that CBLs from lactobacilli are probably involved in methionine biosynthesis. Moreover, the results of this study suggest that post-transcriptional mechanisms account for the differences in CBL activities observed between strains of Lb. delbrueckii.

  9. Relationship between cystathionine γ-lyase gene polymorphism and essential hypertension in Northern Chinese Han population

    Institute of Scientific and Technical Information of China (English)

    LI Yun; ZHAO Qi; LIU Xiao-li; WANG Lai-yuan; LU Xiang-feng; LI Hong-fang; CHEN Shu-feng; HUANG Jian-feng; GU Dong-feng

    2008-01-01

    Background Hydrogen sulfide(H2S)plays an important role in the smooth muscle cell relaxation and thereby participates in the development of hypertension. Cystathionine γ-lyase is the key enzyme in the endogenous production of H2S. Up to now, the reports on the relationship between the polymorphisms of cystathionine γ-lyase gene (CTH) and essential hypertension(EH)are limited. This study was designed to assess their underlying relationship. Methods A total of 503 hypertensive patients and 490 age-, gender-and area-matched normotensive controls were enrolled in this study. Based on the FASTSNP, a web server to identify putative functional single nucleotide polymorphisms (SNPs) of genes, we selected two SNPs, rs482843 and rs1021737, in the CTH gene for genotyping. Genotyping was performed by the polymerase chain reaction and restriction fragment length polymorphism method (PCR-RFLP). The frequencies of the alleles and genotypes between cases and controls were compared by the chi-square test. The program Haplo. stats was used to investigate the relationship between the haplotypes and EH. Results These two SNPs were in Hardy-Weinberg Equilibrium in both cases and controls. The genotype distribution and allele frequencies of them did not significantly differ between cases and controls(all P>0.05). In the stepwise logistic regression analysis we failed to observe their association with hypertension. In addition, none of the four estimated haplotypes or diplotypes significantly increased or decreased the risk of hypertension before or after adjustment for several known risk factors. Conclusions The present study suggests that the SNPs rs482843 and rs1021737 of the CTH gene were not associated with essential hypertension in the Northern Chinese Han population. However, replications in other populations and further functional studies are still necessary to clarify the role of the CTH gene in the pathogenesis of EH.

  10. Association study between cystathione-beta-synthase gene polymorphism and schizophrenia%胱硫醚-β-合成酶基因多态性与精神分裂症的关联研究

    Institute of Scientific and Technical Information of China (English)

    张文跃; 祁小飞; 王梅芬; 宣春明; 顾凤华; 韩晓东

    2009-01-01

    Objective To explore the relationship between cystathione-beta-synthase(CBS) gene T833C,G919A polymorphisms and schizophrenia. Methods The CBS gene polymorphism was detected by polymerase chain reaction and DNA sequencing technique in 93 patients with schizophrenia and 102 healthy people as normal control. Results ⑴ No CBS gene T833C ,G919A polymorphisms were found in all subjects,but mutation of G→A was detected at the 33th base in intron 8-9. Both heterozygote G/A and homozygote A/A were found in patient group,only heterozygote G/A was found in control group. ⑵ There was no significant difference of genotype distribution for mutation of G→A between patient group and control group(P>0.05). The frequency of A allele in patient group (8.07%)was higher than that in control group(3.43%) (χ2=3.92,P=0.048,OR=2.47,95%CI=1.01~6.05). ⑶ There was no significant difference of genotype distribution for mutation of G→A between clinic subgroups and control group(all P>0.05). The frequency of A allele in positive subgroup(8.70%) and later first-onset age subgroup(8.93%) were higher than that in control group(χ2=4.35,P=0.037,OR=2.68,95%CI=1.06~6.77; χ2=4.29,P=0.038,OR=2.76,95%CI=1.06~6.43). Conclusion The finding suggests that mutation of CBS gene T833C ,G919A is very low and it may be not correlated with schizophrenia. Mutation of G→A at the 33th base in intron 8-9 of CBS gene may be one of risk factors for schizophrenia with later first-onset age or positive symptom.%目的 探讨胱硫醚-β-合成酶(CBS) 基因T833C、G919A多态性与精神分裂症的关系.方法 采用聚合酶链式反应(PCR)和DNA测序技术,对93例精神分裂症患者(病例组)和102例正常对照者(对照组)的CBS基因多态性进行检测.结果 ⑴所有受检者均未发现CBS基因T833C、G919A多态性,但在下游8-9内含子33bp处检测到G→A突变;病例组见G/A杂合和A/A纯合,对照组仅见G/A杂合.⑵病例组与对照组在G→A突变的基因型

  11. Effect of Physical Exercise on the Febrigenic Signaling is Modulated by Preoptic Hydrogen Sulfide Production

    National Research Council Canada - National Science Library

    Nogueira, Jonatas E; Soriano, Renato N; Fernandez, Rodrigo A. R; Francescato, Heloísa D. C; Saia, Rafael S; Coimbra, Terezila M; Antunes-Rodrigues, José; Branco, Luiz G. S

    2017-01-01

    ...) of the hypothalamus modulates the febrigenic signaling differently in sedentary and trained rats. Besides H2S production rate and protein expressions of H2S-related synthases cystathionine [Beta]-synthase (CBS...

  12. Cystathionine β-synthase-derived hydrogen sulfide is involved in human malignant hyperthermia.

    Science.gov (United States)

    Vellecco, Valentina; Mancini, Antonio; Ianaro, Angela; Calderone, Vincenzo; Attanasio, Chiara; Cantalupo, Anna; Andria, Barbara; Savoia, Gennaro; Panza, Elisabetta; Di Martino, Antonietta; Cirino, Giuseppe; Bucci, Mariarosaria

    2016-01-01

    Hydrogen sulfide is an endogenous gasotransmitter and its mechanism of action involves activation of ATP-sensitive K(+) channels and phosphodiesterase inhibition. As both mechanisms are potentially involved in malignant hyperthermia (MH), in the present study we addressed the involvement of the L-cysteine/hydrogen sulfide pathway in MH. Skeletal muscle biopsies obtained from 25 MH-susceptible (MHS) and 56 MH-negative (MHN) individuals have been used to perform the in vitro contracture test (IVCT). Quantitative real-time PCR (qPCR) and Western blotting studies have also been performed. Hydrogen sulfide levels are measured in both tissue samples and plasma. In MHS biopsies an increase in cystathionine β-synthase (CBS) occurs, as both mRNA and protein expression compared with MHN biopsies. Hydrogen sulfide biosynthesis is increased in MHS biopsies (0.128±0.12 compared with 0.943±0.13 nmol/mg of protein per min for MHN and MHS biopsies, respectively; Phydrogen sulfide pathway in MH, giving new insight into MH molecular mechanisms. This finding has potential implications for clinical care and could help to define less invasive diagnostic procedures.

  13. Cystathionine β-Synthase Inhibition Is a Potential Therapeutic Approach to Treatment of Ischemic Injury

    Directory of Open Access Journals (Sweden)

    Su Jing Chan

    2015-03-01

    Full Text Available Hydrogen sulfide (H2S has been reported to exacerbate stroke outcome in experimental models. Cystathionine β-synthase (CBS has been implicated as the predominant H2S-producing enzyme in central nervous system. When SH-SY5Y cells were transfected to overexpress CBS, these cells were able to synthesize H2S when exposed to high levels of enzyme substrates but not substrate concentrations that may reflect normal physiological conditions. At the same time, these cells demonstrated exacerbated cell death when subjected to oxygen and glucose deprivation (OGD together with high substrate concentrations, indicating that H2S production has a detrimental effect on cell survival. This effect could be abolished by CBS inhibition. The same effect was observed with primary astrocytes exposed to OGD and high substrates or sodium hydrosulfide. In addition, CBS was upregulated and activated by truncation in primary astrocytes subjected to OGD. When rats were subjected to permanent middle cerebral artery occlusion, CBS activation was also observed. These results imply that in acute ischemic conditions, CBS is upregulated and activated by truncation causing an increased production of H2S, which exacerbate the ischemic injuries. Therefore, CBS inhibition may be a viable approach to stroke treatment.

  14. Mangiferin regulates interleukin-6 and cystathionine-b-synthase in lipopolysaccharide-induced brain injury.

    Science.gov (United States)

    Fu, Yan-Yan; Zhang, Fang; Zhang, Lei; Liu, Hong-Zhi; Zhao, Zi-Ming; Wen, Xiang-Ru; Wu, Jian; Qi, Da-Shi; Sun, Ying; Du, Yang; Dong, Hong-Yan; Liu, Yong-Hai; Song, Yuan-Jian

    2014-07-01

    Mangiferin has been extensively applied in different fields due to its anti-inflammatory properties. However, the precise mechanism used by mangiferin on lipopolysaccharide (LPS)-induced inflammation has not been elucidated. Here, we discuss the potential mechanism of mangiferin during a LPS-induced brain injury. Brain injury was induced in ICR mice via intraperitoneal LPS injection (5 mg/kg). Open- and closed-field tests were used to detect the behaviors of mice, while immunoblotting was performed to measure the expression of interleukin-6 (IL-6) and cystathionine-b-synthase (CBS) in the hippocampus after mangiferin was orally administered (p.o.). Mangiferin relieved LPS-induced sickness 6 and 24 h after LPS injection; in addition, this compound suppressed LPS-induced IL-6 production after 24 h of LPS induction as well as the downregulation of LPS-induced CBS expression after 6 and 24 h of LPS treatment in the hippocampus. Therefore, mangiferin attenuated sickness behavior by regulating the expression of IL-6 and CBS.

  15. Bioenergetic relevance of hydrogen sulfide and the interplay between gasotransmitters at human cystathionine β-synthase.

    Science.gov (United States)

    Vicente, João B; Malagrinò, Francesca; Arese, Marzia; Forte, Elena; Sarti, Paolo; Giuffrè, Alessandro

    2016-08-01

    Merely considered as a toxic gas in the past, hydrogen sulfide (H2S) is currently viewed as the third 'gasotransmitter' in addition to nitric oxide (NO) and carbon monoxide (CO), playing a key signalling role in human (patho)physiology. H2S can either act as a substrate or, similarly to CO and NO, an inhibitor of mitochondrial respiration, in the latter case by targeting cytochrome c oxidase (CcOX). The impact of H(2)S on mitochondrial energy metabolism crucially depends on the bioavailability of this gaseous molecule and its interplay with the other two gasotransmitters. The H(2)S-producing human enzyme cystathionine β-synthase (CBS), sustaining cellular bioenergetics in colorectal cancer cells, plays a role in the interplay between gasotransmitters. The enzyme was indeed recently shown to be negatively modulated by physiological concentrations of CO and NO, particularly in the presence of its allosteric activator S-adenosyl-l-methionine (AdoMet). These newly discovered regulatory mechanisms are herein reviewed. This article is part of a Special Issue entitled 'EBEC 2016: 19th European Bioenergetics Conference, Riva del Garda, Italy, July 2-6, 2016', edited by Prof. Paolo Bernardi.

  16. Cystathionine γ-lyase, a H2S-generating enzyme, is a GPBAR1-regulated gene and contributes to vasodilation caused by secondary bile acids.

    Science.gov (United States)

    Renga, Barbara; Bucci, Mariarosaria; Cipriani, Sabrina; Carino, Adriana; Monti, Maria Chiara; Zampella, Angela; Gargiulo, Antonella; d'Emmanuele di Villa Bianca, Roberta; Distrutti, Eleonora; Fiorucci, Stefano

    2015-07-01

    GPBAR1 is a bile acid-activated receptor (BAR) for secondary bile acids, lithocholic (LCA) and deoxycholic acid (DCA), expressed in the enterohepatic tissues and in the vasculature by endothelial and smooth muscle cells. Despite that bile acids cause vasodilation, it is unclear why these effects involve GPBAR1, and the vascular phenotype of GPBAR1 deficient mice remains poorly defined. Previous studies have suggested a role for nitric oxide (NO) in regulatory activity exerted by GPBAR1 in liver endothelial cells. Hydrogen sulfide (H2S) is a vasodilatory agent generated in endothelial cells by cystathionine-γ-lyase (CSE). Here we demonstrate that GPBAR1 null mice had increased levels of primary and secondary bile acids and impaired vasoconstriction to phenylephrine. In aortic ring preparations, vasodilation caused by chenodeoxycholic acid (CDCA), a weak GPBAR1 ligand and farnesoid-x-receptor agonist (FXR), was iberiotoxin-dependent and GPBAR1-independent. In contrast, vasodilation caused by LCA was GPBAR1 dependent and abrogated by propargyl-glycine, a CSE inhibitor, and by 5β-cholanic acid, a GPBAR1 antagonist, but not by N(5)-(1-iminoethyl)-l-ornithine (l-NIO), an endothelial NO synthase inhibitor, or iberiotoxin, a large-conductance calcium-activated potassium (BKCa) channels antagonist. In venular and aortic endothelial (HUVEC and HAEC) cells GPBAR1 activation increases CSE expression/activity and H2S production. Two cAMP response element binding protein (CREB) sites (CREs) were identified in the CSE promoter. In addition, TLCA stimulates CSE phosphorylation on serine residues. In conclusion we demonstrate that GPBAR1 mediates the vasodilatory activity of LCA and regulates the expression/activity of CSE. Vasodilation caused by CDCA involves BKCa channels. The GPBAR1/CSE pathway might contribute to endothelial dysfunction and hyperdynamic circulation in liver cirrhosis.

  17. Alleviation of Plasma Homocysteine Level by Phytoestrogen α-Zearalanol Might Be Related to the Reduction of Cystathionine β-Synthase Nitration

    Directory of Open Access Journals (Sweden)

    Hui Zhang

    2014-01-01

    Full Text Available Hyperhomocysteinemia is strongly associated with cardiovascular diseases. Previous studies have shown that phytoestrogen α-zearalanol can protect cardiovascular system from hyperhomocysteinemia and ameliorate the level of plasma total homocysteine; however, the underlying mechanisms remain to be clarified. The aim of this research is to investigate the possible molecular mechanisms involved in ameliorating the level of plasma homocysteine by α-zearalanol. By the successfully established diet-induced hyperhomocysteinemia rat models, we found that, after α-zearalanol treatment, the activity of cystathionine β-synthase, the key enzyme in homocysteine metabolism, was significantly elevated and level of nitrative stress in liver was significantly reduced. In correlation with this, results also showed a decreased nitration level of cystathionine β-synthase in liver. Together data implied that alleviation of plasma homocysteine level by phytoestrogen α-zearalanol might be related to the reduction of cystathionine β-synthase nitration.

  18. Localization of cystathionine β synthase in mice ovaries and its expression profile during follicular development

    Institute of Scientific and Technical Information of China (English)

    LIANG Rong; YU Wei-dong; DU Jun-bao; YANG Li-jun; SHANG Mei; GUO Jing-zhu

    2006-01-01

    Background In vitro fertilization (IVF) researches have suggested that cystathionine β synthase (CBS) is involved in oocyte development. However, little is known about the regional and cellular expression patterns of CBS in the ovary. The purpose of this study was to analyze the localization of CBS in mice ovaries and to investigate the expression profile during follicular development.Methods We used in situ hybridization and immunohistochemical analysis to determine CBS expression in the ovaries of female Balb/c mice. Then the follicles were collected from F1 (C57BL × Balb/c) mice and cultured in vitro. With the method of semi-quantitative RT-PCR, we also investigated the expression profile of CBS during follicular development.Results CBS was absent in the oocytes, although it was ubiquitously expressed in the ovary with the strongest expression in follicular cells at all stages. In late antral follicles, CBS expression was markedly higher in granulosa cells located close to the antrum and in cumulus cells around the oocyte. The semi-quantitative RT-PCR showed that CBS mRNA was detected in follicles at all stages in vitro. In cumulus-oocyte complexes superovulated, CBS expression also increased rapidly.Conclusions CBS was located mainly in the follicular cells in the ovaries. The level of CBS expression is high in follicles during folliculogenesis in mice. Differences in the CBS expression profile between oocyte and follicular cells suggest a role for CBS as a mediator in interactions between oocyte and granulosa cells.

  19. Transcriptional Regulation of Cystathionine-γ-Lyase in Endothelial Cells by NADPH Oxidase 4-Dependent Signaling*

    Science.gov (United States)

    Mistry, Rajesh K.; Murray, Thomas V. A.; Prysyazhna, Oleksandra; Martin, Daniel; Burgoyne, Joseph R.; Santos, Celio; Eaton, Philip; Shah, Ajay M.; Brewer, Alison C.

    2016-01-01

    The gasotransmitter, hydrogen sulfide (H2S) is recognized as an important mediator of endothelial cell homeostasis and function that impacts upon vascular tone and blood pressure. Cystathionine-γ-lyase (CSE) is the predominant endothelial generator of H2S, and recent evidence suggests that its transcriptional expression is regulated by the reactive oxygen species, H2O2. However, the cellular source of H2O2 and the redox-dependent molecular signaling pathway that modulates this is not known. We aimed to investigate the role of Nox4, an endothelial generator of H2O2, in the regulation of CSE in endothelial cells. Both gain- and loss-of-function experiments in human endothelial cells in vitro demonstrated Nox4 to be a positive regulator of CSE transcription and protein expression. We demonstrate that this is dependent upon a heme-regulated inhibitor kinase/eIF2α/activating transcription factor 4 (ATF4) signaling module. ATF4 was further demonstrated to bind directly to cis-regulatory sequences within the first intron of CSE to activate transcription. Furthermore, CSE expression was also increased in cardiac microvascular endothelial cells, isolated from endothelial-specific Nox4 transgenic mice, compared with wild-type littermate controls. Using wire myography we demonstrate that endothelial-specific Nox4 transgenic mice exhibit a hypo-contractile phenotype in response to phenylephrine that was abolished when vessels were incubated with a CSE inhibitor, propargylglycine. We, therefore, conclude that Nox4 is a positive transcriptional regulator of CSE in endothelial cells and propose that it may in turn contribute to the regulation of vascular tone via the modulation of H2S production. PMID:26620565

  20. Cystathionine γ-lyase, an enzyme related to the reverse transsulfuration pathway, is functional in Leishmania spp.

    Science.gov (United States)

    Giordana, Lucila; Mantilla, Brian Suárez; Santana, Marianela; Silber, Ariel M; Nowicki, Cristina

    2014-01-01

    Leishmania parasites seem capable of producing cysteine by de novo biosynthesis, similarly to bacteria, some pathogenic protists, and plants. In Leishmania spp., cysteine synthase (CS) and cystathionine β-synthase (CBS) are expected to participate in this metabolic process. Moreover, the reverse transsulfuration pathway (RTP) is also predicted to be operative in this trypanosomatid because CBS also catalyzes the condensation of serine with homocysteine, and a gene encoding a putative cystathionine γ-lyase (CGL) is present in all the sequenced genomes. Our results show that indeed, Leishmania major CGL is able to rescue the wild-type phenotype of a Saccharomyces cerevisiae CGL-null mutant and is susceptible to inhibition by an irreversible CGL inhibitor, DL-propargylglycine (PAG). In Leishmania promastigotes, CGL and CS are cytosolic enzymes. The coexistence of de novo synthesis with the RTP is extremely rare in most living organisms; however, despite this potentially high redundancy in cysteine production, PAG arrests the proliferation of L. major promastigotes with an IC50 of approximately 65 μM. These findings raise new questions regarding the biological role of CGL in these pathogens and indicate the need for understanding the molecular mechanism of PAG action in vivo to identify the potential targets affected by this drug.

  1. Iodine Deficiency

    Science.gov (United States)

    ... 2017 By ATA | Featured , Iodine Deficiency , News Releases , Potassium Iodide (KI) | No Comments IDD NEWSLETTER – February 2017 VOLUME ... 2016 By ATA | Featured , Iodine Deficiency , News Releases , Potassium Iodide (KI) | No Comments IDD NEWSLETTER – November 2015 (PDF ...

  2. A role for glutamate-333 of Saccharomyces cerevisiae cystathionine γ-lyase as a determinant of specificity.

    Science.gov (United States)

    Hopwood, Emily M S; Ahmed, Duale; Aitken, Susan M

    2014-02-01

    Cystathionine γ-lyase (CGL) catalyzes the hydrolysis of l-cystathionine (l-Cth), producing l-cysteine (l-Cys), α-ketobutyrate and ammonia, in the second step of the reverse transsulfuration pathway, which converts l-homocysteine (l-Hcys) to l-Cys. Site-directed variants substituting residues E48 and E333 with alanine, aspartate and glutamine were characterized to probe the roles of these acidic residues, conserved in fungal and mammalian CGL sequences, in the active-site of CGL from Saccharomyces cerevisiae (yCGL). The pH optimum of variants containing the alanine or glutamine substitutions of E333 is increased by 0.4-1.2 pH units, likely due to repositioning of the cofactor and modification of the pKa of the pyridinium nitrogen. The pH profile of yCGL-E48A/E333A resembles that of Escherichia coli cystathionine β-lyase. The effect of substituting E48, E333 or both residues is the 1.3-3, 26-58 and 124-568-fold reduction, respectively, of the catalytic efficiency of l-Cth hydrolysis. The Km(l-Cth) of E333 substitution variants is increased ~17-fold, while Km(l-OAS) is within 2.5-fold of the wild-type enzyme, indicating that residue E333 interacts with the distal amine moiety of l-Cth, which is not present in the alternative substrate O-acetyl-l-serine. The catalytic efficiency of yCGL for α,γ-elimination of O-succinyl-l-homoserine (kcat/Km(l-OSHS)=7±2), which possesses a distal carboxylate, but lacks an amino group, is 300-fold lower than that of the physiological l-Cth substrate (kcat/Km(l-Cth)=2100±100) and 260-fold higher than that of l-Hcys (kcat/Km(l-Hcys)=0.027±0.005), which lacks both distal polar moieties. The results of this study suggest that the glutamate residue at position 333 is a determinant of specificity.

  3. Disaccharidase deficiency.

    Science.gov (United States)

    Bayless, T M; Christopher, N L

    1969-02-01

    This review of the literature and current knowledge concerning a nutritional disorder of disaccharidase deficiency discusses the following topics: 1) a description of disorders of disaccharide digestion; 2) some historical perspective on the laboratory and bedside advances in the past 10 years that have helped define a group of these digestive disorders; 3) a classification of conditions causing disaccharide intolerance; and 4) a discussion of some of the specific clinical syndromes emphasizing nutritional consequences of these syndromes. The syndromes described include congenital lactase deficiency, acquired lactase deficiency in teenagers and adults, acquired generalized disaccharidase deficiency secondary to diffuse mucosal damage, acquired lactose intolerance secondary to alterations in the intestinal transit, sucrase-isomaltase deficiencies, and other disease associations connected with lactase deficiency such as colitis.

  4. Oral exposure to the anti-pyridoxine compound 1-amino D-proline further perturbs homocysteine metabolism through the transsulfuration pathway in moderately vitamin B₆ deficient rats.

    Science.gov (United States)

    Mayengbam, Shyamchand; Raposo, Sara; Aliani, Michel; House, James D

    2015-03-01

    Pyridoxal 5'-phosphate (PLP; a B₆ vitamer) serves as an important cofactor in a myriad of metabolic reactions, including the transsulfuration (TS) pathway, which converts homocysteine (Hcy) to cysteine. While overt vitamin B₆ deficiency is rare, moderate deficiency is common and may be exacerbated by anti-pyridoxine factors in the food supply. To this end, we developed a model of moderate B₆ deficiency and a study was conducted to examine the in vivo effect of 1-amino D-proline (1ADP), an anti-pyridoxine factor found in flaxseed, on indices of Hcy metabolism through the TS pathway in moderately B₆ deficient rats. Male weaning rats received a semi-purified diet containing either 7 mg/kg (control; CD) or 0.7 mg/kg (moderately deficient; MD) diet of pyridoxine·hydrochloride (PN∙HCl), each with 1 of 4 levels of 1ADP, viz. 0, 0.1, 1 and 10 mg/kg diet for 5 weeks. Perturbations in vitamin B₆ biomarkers were more pronounced in the MD group. Plasma PLP was significantly reduced, while plasma Hcy (8-fold) and cystathionine (11-fold) were increased in rats consuming the highest amount of 1ADP in the MD group. The activities of hepatic cystathionine β-synthase and cystathionine γ-lyase enzymes were significantly reduced in rats consuming the highest 1ADP compared to the lowest, for both levels of PN∙HCl. Dilation of hepatic central veins and sinusoids, mild steatosis and increased liver triglycerides were present in MD rats consuming the highest 1ADP level. The current data provide evidence that the consumption of an anti-pyridoxine factor linked to flaxseed may pose a risk for subjects who are moderate/severe vitamin B₆ deficient.

  5. B vitamins and homocysteine in cardiovascular disease and aging.

    Science.gov (United States)

    Wilcken, D E; Wilcken, B

    1998-11-20

    The sulfur-containing amino acid, homocysteine, is formed from the essential amino acid methionine, and a number of B vitamins are involved in methionine metabolism. Pyridoxine, vitamin B6, is a cofactor for cystathionine beta synthase, which mediates the transformation of homocysteine to cystathionine, the initial step in the transsulfuration pathway and the urinary excretion of sulfur. In a normal diet there is conservation of the carbon skeleton, and about 50% of the homocysteine formed is remethylated to methionine via steps that require folic acid and vitamin B12. A deficiency of any of these three vitamins leads to modest homocyst(e)ine elevation, as does diminished renal function, both of which are common in the elderly. It is also established that homocyst(e)ine elevation of this order is associated with increased cardiovascular risk but is also associated with most established risk factors, although it is thought to be an independent contributor. In the inborn error of metabolism homocystinuria due to cystathionine beta synthase deficiency there is greatly increased circulating homocyst(e)ine and a clear association with precocious vascular disease. In about 50% of these patients there is a vascular event before the age of 30 years. The homocysteine-induced adverse vascular changes appear to result from endothelial and smooth muscle cell effects and increased thrombogenesis. We have documented a highly significant reduction in the occurrence of vascular events during 539 patient years of treatment in 32 patients with cystathionine beta synthase deficiency (mean age 30 years, range 9-66 years) by aggressive homocyst(e)ine lowering with pyridoxine, folic acid, and B12 (p = 0.0001). The 15 pyridoxine nonresponsive patients also received oral betaine. Although a cause and effect relationship is postulated for the increased cardiovascular risk associated with mild homocysteine elevation, a common cause of this elevation is the methylenetetrahydrofolate

  6. Prolidase deficiency

    Directory of Open Access Journals (Sweden)

    Masood Qazi

    2007-01-01

    Full Text Available Prolidase deficiency is a rare inborn disorder of collagen metabolism characterized by chronic recurrent skin ulceration. A seven-year-old girl and her younger sibling with clinical features and laboratory criteria fulfilling the diagnosis of prolidase deficiency are presented in view of rarity of the condition.

  7. 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. Howeve

  8. 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. Howeve

  9. Iodine Deficiency

    Science.gov (United States)

    ... 0 Iodine Daily Serving now recommended in Multivitamin/Mineral Supplements for Pregnant and Lactating Women By ATA | 2015 News Releases , Iodine Deficiency , News Releases , Thyroid Disease and Pregnancy | No Comments Falls Church, February 10, 2015 —The ...

  10. Iron deficiency.

    Science.gov (United States)

    Scrimshaw, N S

    1991-10-01

    The world's leading nutritional problem is iron deficiency. 66% of children and women aged 15-44 years in developing countries have it. Further, 10-20% of women of childbearing age in developed countries are anemic. Iron deficiency is identified with often irreversible impairment of a child's learning ability. It is also associated with low capacity for adults to work which reduces productivity. In addition, it impairs the immune system which reduces the body's ability to fight infection. Iron deficiency also lowers the metabolic rate and the body temperature when exposed to cold. Hemoglobin contains nearly 73% of the body's iron. This iron is always being recycled as more red blood cells are made. The rest of the needed iron does important tasks for the body, such as binds to molecules that are reservoirs of oxygen for muscle cells. This iron comes from our diet, especially meat. Even though some plants, such as spinach, are high in iron, the body can only absorb 1.4-7% of the iron in plants whereas it can absorb 20% of the iron in red meat. In many developing countries, the common vegetarian diets contribute to high rates of iron deficiency. Parasitic diseases and abnormal uterine bleeding also promote iron deficiency. Iron therapy in anemic children can often, but not always, improve behavior and cognitive performance. Iron deficiency during pregnancy often contributes to maternal and perinatal mortality. Yet treatment, if given to a child in time, can lead to normal growth and hinder infections. However, excess iron can be damaging. Too much supplemental iron in a malnourished child promotes fatal infections since the excess iron is available for the pathogens use. Many countries do not have an effective system for diagnosing, treating, and preventing iron deficiency. Therefore a concerted international effort is needed to eliminate iron deficiency in the world.

  11. Hydrogen sulfide-mediated regulation of contractility in the mouse ileum with electrical stimulation: roles of L-cysteine, cystathionine β-synthase, and K+ channels.

    Science.gov (United States)

    Yamane, Satoshi; Kanno, Toshio; Nakamura, Hiroyuki; Fujino, Hiromichi; Murayama, Toshihiko

    2014-10-01

    Hydrogen sulfide (H2S) is considered to be a signaling molecule. The precise mechanisms underlying H2S-related events, including the producing enzymes and target molecules in gastrointestinal tissues, have not been elucidated in detail. We herein examined the involvement of H2S in contractions induced by repeated electrical stimulations (ES). ES-induced contractions were neurotoxin-sensitive and increased by aminooxyacetic acid, an inhibitor of cystathionine β-synthase (CBS) and cystathionine γ-lyase, but not by D,L-propargylglycine, a selective inhibitor of cystathionine γ-lyase, in an ES trial-dependent manner. ES-induced contractions were markedly decreased in the presence of L-cysteine. This response was inhibited by aminooxyacetic acid and an antioxidant, and accelerated by L-methionine, an activator of CBS. The existence of CBS was confirmed. NaHS transiently inhibited ES- and acetylcholine-induced contractions, and sustainably decreased basal tone for at least 20 min after its addition. The treatment with glibenclamide, an ATP-sensitive K+ channel blocker, reduced both the L-cysteine response and NaHS-induced inhibition of contractions. The NaHS-induced decrease in basal tone was inhibited by apamin, a small conductance Ca2+-activated K+ channel blocker. These results suggest that H2S may be endogenously produced via CBS in ES-activated enteric neurons, and regulates contractility via multiple K+ channels in the ileum.

  12. Thioethers as markers of hydrogen sulfide production in homocystinurias.

    Science.gov (United States)

    Kožich, Viktor; Krijt, Jakub; Sokolová, Jitka; Melenovská, Petra; Ješina, Pavel; Vozdek, Roman; Majtán, Tomáš; Kraus, Jan P

    2016-07-01

    Two enzymes in the transsulfuration pathway of homocysteine -cystathionine beta-synthase (CBS) and gamma-cystathionase (CTH)-use cysteine and/or homocysteine to produce the important signaling molecule hydrogen sulfide (H2S) and simultaneously the thioethers lanthionine, cystathionine or homolanthionine. In this study we explored whether impaired flux of substrates for H2S synthesis and/or deficient enzyme activities alter production of hydrogen sulfide in patients with homocystinurias. As an indirect measure of H2S synthesis we determined by LC-MS/MS concentrations of thioethers in plasma samples from 33 patients with different types of homocystinurias, in 8 patient derived fibroblast cell lines, and as reaction products of seven purified mutant CBS enzymes. Since chaperoned recombinant mutant CBS enzymes retained capacity of H2S synthesis in vitro it can be stipulated that deficient CBS activity in vivo may impair H2S production. Indeed, in patients with classical homocystinuria we observed significantly decreased cystathionine and lanthionine concentrations in plasma (46% and 74% of median control levels, respectively) and significantly lower cystathionine in fibroblasts (8% of median control concentrations) indicating that H2S production from cysteine and homocysteine may be also impaired. In contrast, the grossly elevated plasma levels of homolanthionine in CBS deficient patients (32-times elevation compared to median of controls) clearly demonstrates a simultaneous overproduction of H2S from homocysteine by CTH. In the remethylation defects the accumulation of homocysteine and the increased flux of metabolites through the transsulfuration pathway resulted in elevation of cystathionine and homolanthionine (857% and 400% of median control values, respectively) indicating a possibility of an increased biosynthesis of H2S by both CBS and CTH. This study shows clearly disturbed thioether concentrations in homocystinurias, and modeling using these data indicates

  13. Differential effects of cystathionine-γ-lyase-dependent vasodilatory H2S in periadventitial vasoregulation of rat and mouse aortas.

    Directory of Open Access Journals (Sweden)

    Carolin Köhn

    Full Text Available BACKGROUND: Hydrogen sulfide (H(2S is a potent vasodilator. However, the complex mechanisms of vasoregulation by H(2S are not fully understood. We tested the hypotheses that (1 H(2S exerts vasodilatory effects by opening KCNQ-type voltage-dependent (K(v K(+ channels and (2 that H(2S-producing cystathionine-γ-lyase (CSE in perivascular adipose tissue plays a major role in this pathway. METHODOLOGY/PRINCIPAL FINDINGS: Wire myography of rat and mouse aortas was used. NaHS and 5-(4-hydroxyphenyl-3H-1,2-dithiole-3-thione (ADTOH were used as H(2S donors. KCNQ-type K(v channels were blocked by XE991. 4-Propargylglycine (PPG and ß-cyano-l-alanine (BCA, or 2-(aminooxy-acetic acid (AOAA were used as inhibitors of CSE or cystathionine-ß-synthase (CBS, respectively. NaHS and ADTOH produced strong vasorelaxation in rat and mouse aortas, which were abolished by KCNQ channel inhibition with XE991. Perivascular adipose tissue (PVAT exerted an anticontractile effect in these arteries. CSE inhibition by PPG and BCA reduced this effect in aortas from rats but not from mice. CBS inhibition with AOAA did not inhibit the anticontractile effects of PVAT. XE991, however, almost completely suppressed the anticontractile effects of PVAT in both species. Exogenous l-cysteine, substrate for the endogenous production of H(2S, induced vasorelaxation only at concentrations >5 mmol/l, an effect unchanged by CSE inhibition. CONCLUSIONS/SIGNFICANCE: Our results demonstrate potent vasorelaxant effects of H(2S donors in large arteries of both rats and mice, in which XE991-sensitive KCNQ-type channel opening play a pivotal role. CSE-H(2S seems to modulate the effect of adipocyte-derived relaxing factor in rat but not in mouse aorta. The present study provides novel insight into the interaction of CSE-H(2S and perivascular adipose tissue. Furthermore, with additional technical advances, a future clinical approach targeting vascular H(2S/KCNQ pathways to influence states of

  14. Biochemical Stability and Molecular Dynamic Characterization of Aspergillus fumigatus Cystathionine γ-Lyase in Response to Various Reaction Effectors

    KAUST Repository

    El-Sayed, Ashraf S.A.

    2015-08-11

    Cystathionine γ-lyase (CGL) is a key enzyme in the methionine-cysteine cycle in all living organisms forming cysteine, α-ketobutyrate and ammonia via homocysteine and cystathionine intermediates. Although, human and plant CGLs have been extensively studied at the molecular and mechanistic levels, there has been little work on the molecular and catalytic properties of fungal CGL. Herein, we studied in detail for the first time the molecular and catalytic stability of Aspergillus fumigatus CGL, since conformational instability, inactivation and structural antigenicity are the main limitations of the PLP-dependent enzymes on various therapeutic uses. We examined these properties in response to buffer compositions, stabilizing and destabilizing agents using Differential Scanning Fluorometery (DSF), steady state and gel-based fluorescence of the intrinsic hydrophobic core, stability of internal aldimine linkage and catalytic properties. The activity of the recombinant A. fumigatus CGL was 13.8 U/mg. The melting temperature (Tm) of CGL in potassium phosphate buffer (pH 7.0-8.0) was 73.3 °C, with ∼3 °C upshifting in MES and sodium phosphate buffers (pH 7.0). The conformational thermal stability was increased in potassium phosphate, sodium phosphate and MES buffers, in contrast to Tris-HCl, HEPES (pH 7.0) and CAPS (pH 9.0-10.0). The thermal stability and activity of CGL was slightly increased in the presence of trehalose and glycerol that might be due to hydration of the enzyme backbone, unlike the denaturing effect of GdmCl and urea. Modification of surface CGL glutamic and aspartic acids had no significant effect on the enzyme conformational and catalytic stability. Molecular modeling and dynamics simulations unveil the high conformational stability of the overall scaffold of CGL with high flexibility at the non-structural regions. CGL structure has eight buried Trp residues, which are reoriented to the enzyme surface and get exposed to the solvent under

  15. Biochemical stability and molecular dynamic characterization of Aspergillus fumigatus cystathionine γ-lyase in response to various reaction effectors.

    Science.gov (United States)

    El-Sayed, Ashraf S A; Abdel-Azeim, Safwat; Ibrahim, Hend M; Yassin, Marwa A; Abdel-Ghany, Salah E; Esener, Sadik; Ali, Gul Shad

    2015-12-01

    Cystathionine γ-lyase (CGL) is a key enzyme in the methionine-cysteine cycle in all living organisms forming cysteine, α-ketobutyrate and ammonia via homocysteine and cystathionine intermediates. Although, human and plant CGLs have been extensively studied at the molecular and mechanistic levels, there has been little work on the molecular and catalytic properties of fungal CGL. Herein, we studied in detail for the first time the molecular and catalytic stability of Aspergillus fumigatus CGL, since conformational instability, inactivation and structural antigenicity are the main limitations of the PLP-dependent enzymes on various therapeutic uses. We examined these properties in response to buffer compositions, stabilizing and destabilizing agents using Differential Scanning Fluorometery (DSF), steady state and gel-based fluorescence of the intrinsic hydrophobic core, stability of internal aldimine linkage and catalytic properties. The activity of the recombinant A. fumigatus CGL was 13.8U/mg. The melting temperature (Tm) of CGL in potassium phosphate buffer (pH 7.0-8.0) was 73.3°C, with ∼3°C upshifting in MES and sodium phosphate buffers (pH 7.0). The conformational thermal stability was increased in potassium phosphate, sodium phosphate and MES buffers, in contrast to Tris-HCl, HEPES (pH 7.0) and CAPS (pH 9.0-10.0). The thermal stability and activity of CGL was slightly increased in the presence of trehalose and glycerol that might be due to hydration of the enzyme backbone, unlike the denaturing effect of GdmCl and urea. Modification of surface CGL glutamic and aspartic acids had no significant effect on the enzyme conformational and catalytic stability. Molecular modeling and dynamics simulations unveil the high conformational stability of the overall scaffold of CGL with high flexibility at the non-structural regions. CGL structure has eight buried Trp residues, which are reoriented to the enzyme surface and get exposed to the solvent under perturbation

  16. Panax Notoginseng Saponins Ameliorates Coxsackievirus B3-Induced Myocarditis by Activating the Cystathionine-γ-Lyase/Hydrogen Sulfide Pathway.

    Science.gov (United States)

    Pan, Lulu; Zhang, Yuanhai; Lu, Jiacheng; Geng, Zhimin; Jia, Lianhong; Rong, Xing; Wang, Zhenquan; Zhao, Qifeng; Wu, Rongzhou; Chu, Maoping; Zhang, Chunxiang

    2015-12-01

    This study is to determine the therapeutic effects of Panax notoginseng saponins (PNSs) on coxsackievirus B3 (CVB3)-induced myocarditis, and whether cystathionine-γ-lyase (CSE)/hydrogen sulfide (H2S) pathway is involved. Mouse model of myocarditis was induced by CVB3 infection, and the mice were subjected to vehicle (saline) or drug treatments (sodium bisulfide (NaHS), propargylglycine (PAG), or PNSs). The results showed that there were inflammatory cell infiltrations, interstitial edemas, and elevated inflammatory cytokines, in CVB3-induced myocarditis. PAG administration increased, whereas NaHS treatment decreased the severity of the myocarditis. PNS treatment dramatically alleviated these myocardial injuries and decreased the viral messenger RNA (mRNA) expression by the enhanced expression of CSE/H2S pathway. Moreover, the therapeutic effects of PNSs on myocarditis were stronger than those of NaHS. Finally, the effect of PNSs on CSE/H2S pathway and cardiac cell protection were verified in cultured cardiac cells. PNSs may be a promising medication for viral myocarditis therapy.

  17. Dose and time-dependent effects of cyanide on thiosulfate sulfurtransferase, 3-mercaptopyruvate sulfurtransferase, and cystathionine λ-lyase activities.

    Science.gov (United States)

    Singh, Poonam; Rao, Pooja; Bhattacharya, Rahul

    2013-12-01

    We assessed the dose-dependent effect of potassium cyanide (KCN) on thiosulfate sulfurtransferase (TST), 3-mercaptopyruvate sulfurtransferase (3-MPST), and cystathionine λ-lyase (CST) activities in mice. The time-dependent effect of 0.5 LD50 KCN on cyanide level and cytochrome c oxidase (CCO), TST, 3-MPST, and CST activities was also examined. Furthermore, TST, 3-MPST, and CST activities were measured in stored mice cadavers. Hepatic and renal TST activity increased by 0.5 LD50 KCN but diminished by ≥2.0 LD50. After 0.5 LD50 KCN, the elevated hepatic cyanide level was accompanied by increased TST, 3-MPST, and CST activities, and CCO inhibition. Elevated renal cyanide level was only accompanied by increased 3-MPST activity. No appreciable change in enzyme activities was observed in mice cadavers. The study concludes that high doses of cyanide exert saturating effects on its detoxification enzymes, indicating their exogenous use during cyanide poisoning. Also, these enzymes are not reliable markers of cyanide poisoning in autopsied samples. © 2013 Wiley Periodicals, Inc.

  18. Mg2+-dependent Interactions of ATP with the Cystathionine-β-Synthase (CBS) Domains of a Magnesium Transporter*

    Science.gov (United States)

    Hirata, Yusuke; Funato, Yosuke; Takano, Yu; Miki, Hiroaki

    2014-01-01

    Ancient conserved domain protein/cyclin M (CNNM) family proteins are evolutionarily conserved Mg2+ transporters. However, their biochemical mechanism of action remains unknown. Here, we show the functional importance of the commonly conserved cystathionine-β-synthase (CBS) domains and reveal their unique binding ability to ATP. Deletion mutants of CNNM2 and CNNM4, lacking the CBS domains, are unable to promote Mg2+ efflux. Furthermore, the substitution of one amino acid residue in the CBS domains of CNNM2, which is associated with human hereditary hypomagnesemia, abrogates Mg2+ efflux. Binding analyses reveal that the CBS domains of CNNM2 bind directly to ATP and not AMP in a manner dependent on the presence of Mg2+, which is inhibited in a similar pattern by the disease-associated amino acid substitution. The requirement of Mg2+ for these interactions is a unique feature among CBS domains, which can be explained by the presence of highly electronegative surface potentials around the ATP binding site on CNNM2. These results demonstrate that the CBS domains play essential roles in Mg2+ efflux, probably through interactions with ATP. Interactions with ATP, which mostly forms complexes with Mg2+ in cells, may account for the rapid Mg2+ transport by CNNM family proteins. PMID:24706765

  19. Mg2+-dependent interactions of ATP with the cystathionine-β-synthase (CBS) domains of a magnesium transporter.

    Science.gov (United States)

    Hirata, Yusuke; Funato, Yosuke; Takano, Yu; Miki, Hiroaki

    2014-05-23

    Ancient conserved domain protein/cyclin M (CNNM) family proteins are evolutionarily conserved Mg(2+) transporters. However, their biochemical mechanism of action remains unknown. Here, we show the functional importance of the commonly conserved cystathionine-β-synthase (CBS) domains and reveal their unique binding ability to ATP. Deletion mutants of CNNM2 and CNNM4, lacking the CBS domains, are unable to promote Mg(2+) efflux. Furthermore, the substitution of one amino acid residue in the CBS domains of CNNM2, which is associated with human hereditary hypomagnesemia, abrogates Mg(2+) efflux. Binding analyses reveal that the CBS domains of CNNM2 bind directly to ATP and not AMP in a manner dependent on the presence of Mg(2+), which is inhibited in a similar pattern by the disease-associated amino acid substitution. The requirement of Mg(2+) for these interactions is a unique feature among CBS domains, which can be explained by the presence of highly electronegative surface potentials around the ATP binding site on CNNM2. These results demonstrate that the CBS domains play essential roles in Mg(2+) efflux, probably through interactions with ATP. Interactions with ATP, which mostly forms complexes with Mg(2+) in cells, may account for the rapid Mg(2+) transport by CNNM family proteins. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  20. Cystathionine-γ lyase-derived hydrogen sulfide mediates the cardiovascular protective effects of moxonidine in diabetic rats.

    Science.gov (United States)

    El-Sayed, Shaimaa S; Zakaria, Mohamed N M; Abdel-Ghany, Rasha H; Abdel-Rahman, Abdel A

    2016-07-15

    Blunted cystathionine-γ lyase (CSE) activity (reduced endogenous H2S-level) is implicated in hypertension and myocardial dysfunction in diabetes. Here, we tested the hypothesis that CSE derived H2S mediates the cardiovascular protection conferred by the imidazoline I1 receptor agonist moxonidine in a diabetic rat model. We utilized streptozotocin (STZ; 55mg/kg i.p) to induce diabetes in male Wistar rats. Four weeks later, STZ-treated rats received vehicle, moxonidine (2 or 6mg/kg; gavage), CSE inhibitor DL-propargylglycine, (37.5mg/kg i.p) or DL-propargylglycine with moxonidine (6mg/kg) for 3 weeks. Moxonidine improved the glycemic state, and reversed myocardial hypertrophy, hypertension and baroreflex dysfunction in STZ-treated rats. Ex vivo studies revealed that STZ caused reductions in CSE expression/activity, H2S and nitric oxide (NO) levels and serum adiponectin and elevations in myocardial imidazoline I1 receptor expression, p38 and extracellular signal-regulated kinase, ERK1/2, phosphorylation and lipid peroxidation (expressed as malondialdehyde). Moxonidine reversed these biochemical responses, and suppressed the expression of death associated protein kinase-3. Finally, pharmacologic CSE inhibition (DL-propargylglycine) abrogated the favorable cardiovascular, glycemic and biochemical responses elicited by moxonidine. These findings present the first evidence for a mechanistic role for CSE derived H2S in the glycemic control and in the favorable cardiovascular effects conferred by imidazoline I1 receptor activation (moxonidine) in a diabetic rat model.

  1. Structural Snapshots of an Engineered Cystathionine-γ-lyase Reveal the Critical Role of Electrostatic Interactions in the Active Site

    Energy Technology Data Exchange (ETDEWEB)

    Yan, Wupeng; Stone, Everett; Zhang, Yan Jessie

    2017-02-01

    Enzyme therapeutics that can degrade l-methionine (l-Met) are of great interest as numerous malignancies are exquisitely sensitive to l-Met depletion. To exhaust the pool of methionine in human serum, we previously engineered an l-Met-degrading enzyme based on the human cystathionine-γ-lyase scaffold (hCGL-NLV) to circumvent immunogenicity and stability issues observed in the preclinical application of bacterially derived methionine-γ-lyases. To gain further insights into the structure–activity relationships governing the chemistry of the hCGL-NLV lead molecule, we undertook a biophysical characterization campaign that captured crystal structures (2.2 Å) of hCGL-NLV with distinct reaction intermediates, including internal aldimine, substrate-bound, gem-diamine, and external aldimine forms. Curiously, an alternate form of hCGL-NLV that crystallized under higher-salt conditions revealed a locally unfolded active site, correlating with inhibition of activity as a function of ionic strength. Subsequent mutational and kinetic experiments pinpointed that a salt bridge between the phosphate of the essential cofactor pyridoxal 5'-phosphate (PLP) and residue R62 plays an important role in catalyzing β- and γ-eliminations. Our study suggests that solvent ions such as NaCl disrupt electrostatic interactions between R62 and PLP, decreasing catalytic efficiency.

  2. Increased Nicotinamide Phosphoribosyltransferase and Cystathionine-β-Synthase in Renal Oncocytomas, Renal Urothelial Carcinoma, and Renal Clear Cell Carcinoma.

    Science.gov (United States)

    Shackelford, Rodney E; Abdulsattar, Jehan; Wei, Eric X; Cotelingam, James; Coppola, Domenico; Herrera, Guillermo A

    2017-07-01

    Renal oncocytomas (ROs), and clear cell (RCC) and urothelial carcinomas (UC), are common renal neoplasms. Nicotinamide phosphoribosyltransferase (Nampt) catalyzes the rate-limiting step of NAD(+) synthesis and its expression is increased in several tumors. Nampt concomitantly regulates hydrogen sulfide (H2S)-synthesizing enzyme levels, including cystathionine-β-synthase (CBS). We used tissue microarrays to examine Nampt and the H2S-synthesizing enzyme CBS protein levels in benign kidney, RCC, UC and ROs. Compared to benign kidney, all three neoplasms showed increased Nampt and CBS protein levels, with the levels increasing in RCC at higher Fuhrman grades. H2S is known to ameliorate chronic renal failure but, as yet, no role for H2S in renal neoplasia has been demonstrated. Here, we showed, for the first time, that Nampt, CBS and, likely, H2S likely play a role in malignant and benign neoplastic renal disease. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  3. Cobalamin deficiency.

    Science.gov (United States)

    Herrmann, Wolfgang; Obeid, Rima

    2012-01-01

    Cobalamin (Cbl, vitamin B12) consists of a corrinoid structure with cobalt in the centre of the molecule. Neither humans nor animals are able to synthesize this vitamin. Foods of animal source are the only natural source of cobalamin in human diet. There are only two enzymatic reactions in mammalian cells that require cobalamin as cofactor. Methylcobolamin is a cofactor for methionine synthase. The enzyme methylmalonyl-CoA-mutase requires adenosylcobalamin as a cofactor. Therefore, serum concentrations of homocysteine (tHcy) and methylmalonic acid (MMA) will increase in cobalamin deficiency. The cobalamin absorption from diet is a complex process that involves different proteins: haptocorrin, intrinsic factor and transcobalamin (TC). Cobalamin that is bound to TC is called holotranscobalamin (holoTC) which is the metabolically active vitamin B12 fraction. HoloTC consists 6 and 20% of total cobalamin whereas 80% of total serum cobalamin is bound to another binding protein, haptocorrin. Cobalamin deficiency is common worldwide. Cobalamin malabsorption is common in elderly subjects which might explain low vitamin status. Subjects who ingest low amount of cobalamin like vegetarians develop vitamin deficiency. No single parameter can be used to diagnose cobalamin deficiency. Total serum cobalamin is neither sensitive nor it is specific for cobalamin deficiency. This might explain why many deficient subjects would be overlooked by utilizing total cobalamin as status marker. Concentration of holotranscobalamin (holoTC) in serum is an earlier marker that becomes decreased before total serum cobalamin. Concentrations of MMA and tHcy increase in blood of cobalamin deficient subjects. Despite limitations of these markers in patients with renal dysfunction, concentrations of MMA and tHcy are useful functional markers of cobalamin status. The combined use of holoTC and MMA assays may better indicate cobalamin status than either of them. Because Cbl deficiency is a risk factor

  4. Lack of global epigenetic methylation defects in CBS deficient mice.

    Science.gov (United States)

    Lee, Hyung-Ok; Wang, Liqun; Kuo, Yin-Ming; Gupta, Sapna; Slifker, Michael J; Li, Yue-Sheng; Andrews, Andrew J; Kruger, Warren D

    2017-01-01

    Cystathionine β-synthase (CBS) deficiency is a recessive inborn error of metabolism in which patients have extremely elevated plasma total homocysteine and have clinical manifestations in the vascular, visual, skeletal, and nervous systems. Homocysteine is an intermediary metabolite produced from the hydrolysis of S-adenosylhomocysteine (SAH), which is a by-product of methylation reactions involving the methyl-donor S-adenosylmethionine (SAM). Here, we have measured SAM, SAH, DNA and histone methylation status in an inducible mouse model of CBS deficiency to test the hypothesis that homocysteine-related phenotypes are caused by inhibition of methylation due to elevated SAH and reduced SAM/SAH ratio. We found that mice lacking CBS have elevated cellular SAH and reduced SAM/SAH ratios in both liver and kidney, but this was not associated with alterations in the level of 5-methylcytosine or various histone modifications. Using methylated DNA immunoprecipitation in combination with microarray, we found that of the 241 most differentially methylated promoter probes, 89 % were actually hypermethylated in CBS deficient mice. In addition, we did not find that changes in DNA methylation correlated well with changes in RNA expression in the livers of induced and uninduced CBS mice. Our data indicates that reduction in the SAM/SAH ratio, due to loss of CBS activity, does not result in overall hypomethylation of either DNA or histones.

  5. 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...

  6. Dysregulation of cystathionine γ-lyase (CSE)/hydrogen sulfide pathway contributes to ox-LDL-induced inflammation in macrophage.

    Science.gov (United States)

    Wang, Xian-Hui; Wang, Fen; You, Shou-Jiang; Cao, Yong-Jun; Cao, Li-Dan; Han, Qiao; Liu, Chun-Feng; Hu, Li-Fang

    2013-11-01

    Hydrogen sulfide (H2S), mainly produced by cystathionine γ-lyase (CSE) in vascular system, emerges as a novel gasotransmitter exerting anti-inflammatory and anti-atherosclerotic effects. Alterations of CSE/H2S pathway may thus be involved in atherosclerosis pathogenesis. However, the underlying mechanisms are poorly understood. The present study showed that the levels of CSE mRNA and protein expression, as well as H2S production were decreased in ox-LDL-treated macrophage. CSE overexpression reduced the ox-LDL-stimulated tumor necrosis factor-α (TNF-α) generation in Raw264.7 and primary macrophage while CSE knockdown enhanced it. Exogenous supplementation of H2S with NaHS and Na2S also decreased the production of TNF-α and intercellular adhesion molecule-1 (ICAM-1) in ox-LDL-stimulated macrophage, and alleviated the adhesion of macrophage to endothelial monolayer. Cysteine, a CSE preferential substrate for H2S biosynthesis, produced similar effects on the pro-inflammatory cytokine generation, which were reversed by CSE inhibitors PAG and BCA, respectively. Moreover, NaHS and Na2S attenuated the phosphorylation and degradation of IκBα and p65 nuclear translocation, as well as JNK activation caused by ox-LDL. The JNK inhibitor suppressed the NF-κB transcription activity in ox-LDL-treated cells. Furthermore, inhibitors of NF-κB (PDTC), ERK (U0126 and PD98059) and JNK (SP600125) partially blocked the suppression by ox-LDL on the CSE mRNA levels. Taken together, the findings demonstrate that ox-LDL may down-regulate the CSE/H2S pathway, which plays an anti-inflammatory role in ox-LDL-stimulated macrophage by suppressing JNK/NF-κB signaling. The study reveals new therapeutic strategies for atherosclerosis, based on modulating CSE/H2S pathway.

  7. Downregulation of cystathionine β-synthase/hydrogen sulfide contributes to rotenone-induced microglia polarization toward M1 type.

    Science.gov (United States)

    Du, Chenchen; Jin, Mengmeng; Hong, Yu; Li, Qian; Wang, Xian-Hui; Xu, Jin-Min; Wang, Fen; Zhang, Ye; Jia, Jia; Liu, Chun-Feng; Hu, Li-Fang

    2014-08-22

    Microglia-mediated neuroinflammation is implicated in the pathogenesis of several neurodegenerative disorders. Microglia can be activated and polarized to exert pro- or anti-inflammatory roles in response to specific stimulus. Rotenone is an environmental toxin that has been shown to activate microglia and neuroinflammation. However, the effects and mechanisms of rotenone on microglia polarization are poorly studied. In the present study, we demonstrated that rotenone enhanced the levels of M1 phenotypic genes including TNF-α, iNOS and COX-2/PGE2 but reduced that of M2 markers such as Ym1/2 and IL-10 in mouse primary and immortalized microglia. Moreover, the transcription and protein expression of cystathionine-β-synthase (CBS), as well as hydrogen sulfide (H2S) production were decreased in rotenone-treated primary microglia. Elevating endogenous H2S via CBS over-expression in immortalized microglia not only reduced the expression of pro-inflammatory M1 genes, but also enhanced the anti-inflammatory M2 marker IL-10 production in response to rotenone stimulation as compared to vector-transfected cells. Similarly, pretreatment with H2S donor NaHS (50, 100 and 500μmol/L) attenuated the increases of M1 gene expression triggered by rotenone treatment, and enhanced the M2 gene Ym1/2 expression in mouse primary microglia. In addition, we observed reactive oxygen species (ROS) scavenger N-acetyl-l-cysteine reversed the down-regulation of CBS and H2S generation caused by rotenone in microglia. NaHS pretreatment also decreased the ROS formation in rotenone-stimulated microglia. Taken together, these results reveal that probably via triggering ROS formation, rotenone suppressed the CBS-H2S pathway and thus promoted microglia polarization toward M1 pro-inflammatory phenotype.

  8. Cystathionine β-Synthase (CBS) Domain-containing Pyrophosphatase as a Target for Diadenosine Polyphosphates in Bacteria.

    Science.gov (United States)

    Anashkin, Viktor A; Salminen, Anu; Tuominen, Heidi K; Orlov, Victor N; Lahti, Reijo; Baykov, Alexander A

    2015-11-13

    Among numerous proteins containing pairs of regulatory cystathionine β-synthase (CBS) domains, family II pyrophosphatases (CBS-PPases) are unique in that they generally contain an additional DRTGG domain between the CBS domains. Adenine nucleotides bind to the CBS domains in CBS-PPases in a positively cooperative manner, resulting in enzyme inhibition (AMP or ADP) or activation (ATP). Here we show that linear P(1),P(n)-diadenosine 5'-polyphosphates (ApnAs, where n is the number of phosphate residues) bind with nanomolar affinity to DRTGG domain-containing CBS-PPases of Desulfitobacterium hafniense, Clostridium novyi, and Clostridium perfringens and increase their activity up to 30-, 5-, and 7-fold, respectively. Ap4A, Ap5A, and Ap6A bound noncooperatively and with similarly high affinities to CBS-PPases, whereas Ap3A bound in a positively cooperative manner and with lower affinity, like mononucleotides. All ApnAs abolished kinetic cooperativity (non-Michaelian behavior) of CBS-PPases. The enthalpy change and binding stoichiometry, as determined by isothermal calorimetry, were ~10 kcal/mol nucleotide and 1 mol/mol enzyme dimer for Ap4A and Ap5A but 5.5 kcal/mol and 2 mol/mol for Ap3A, AMP, ADP, and ATP, suggesting different binding modes for the two nucleotide groups. In contrast, Eggerthella lenta and Moorella thermoacetica CBS-PPases, which contain no DRTGG domain, were not affected by ApnAs and showed no enthalpy change, indicating the importance of the DTRGG domain for ApnA binding. These findings suggest that ApnAs can control CBS-PPase activity and hence affect pyrophosphate level and biosynthetic activity in bacteria. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  9. Cystathionine β-synthase (CBS) domains confer multiple forms of Mg2+-dependent cooperativity to family II pyrophosphatases.

    Science.gov (United States)

    Salminen, Anu; Anashkin, Viktor A; Lahti, Matti; Tuominen, Heidi K; Lahti, Reijo; Baykov, Alexander A

    2014-08-15

    Regulated family II pyrophosphatases (CBS-PPases) contain a nucleotide-binding insert comprising a pair of cystathionine β-synthase (CBS) domains, termed a Bateman module. By binding with high affinity to the CBS domains, AMP and ADP usually inhibit the enzyme, whereas ATP activates it. Here, we demonstrate that AMP, ADP, and ATP bind in a positively cooperative manner to CBS-PPases from four bacteria: Desulfitobacterium hafniense, Clostridium novyi, Clostridium perfringens, and Eggerthella lenta. Enzyme interaction with substrate as characterized by the Michaelis constant (Km) also exhibited positive catalytic cooperativity that decreased in magnitude upon nucleotide binding. The degree of both types of cooperativity increased with increasing concentration of the cofactor Mg(2+) except for the C. novyi PPase where Mg(2+) produced the opposite effect on kinetic cooperativity. Further exceptions from these general rules were ADP binding to C. novyi PPase and AMP binding to E. lenta PPase, neither of which had any effect on activity. A genetically engineered deletion variant of D. hafniense PPase lacking the regulatory insert was fully active but differed from the wild-type enzyme in that it was insensitive to nucleotides and bound substrate non-cooperatively and with a smaller Km value. These results indicate that the regulatory insert acts as an internal inhibitor and confers dual positive cooperativity to CBS domain-containing PPases, making them highly sensitive regulators of the PPi level in response to the changes in cell energy status that control adenine nucleotide distribution. These regulatory features may be common among other CBS domain-containing proteins. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  10. Novel alleles of 31-bp VNTR polymorphism in the human cystathionine -synthase (CBS) gene were detected in healthy Asians

    Indian Academy of Sciences (India)

    Yik-Yuen Gan; Chuan-Fei Chen

    2010-12-01

    A 31-bp variable number of tandem repeats (VNTR) polymorphism of the cystathionine -synthase (CBS) gene was earlier reported in Caucasians of predominantly European descent and Indo–Caucasoid populations.We report here for the first time, the detection of allele 20, which was absent in Caucasian and Indo–Caucasoid populations, as a common allele present in Singaporean Chinese (6.25%), Indians (11.7%), and Malays (11.5%). Hence, allele 20 might be a specific allele for Asian populations. A relatively common allele 19 found in the Caucasian and Indo–Caucasoid populations (10.4%–10.6%) was absent in the Asian samples of this study. Therefore, allele 19 might be a specific allele for the Caucasian populations. A novel and rare allele 13, which was not reported before in the Caucasian and Indo–Caucasoid populations, was found in 0.5% of Singaporean Chinese as genotype 13/17 heterozygotes. The presence of alleles 13 and 20 were verified by DNA sequencing. There were five new genotypes (13/17, 16/20, 17/20, 18/20 and 20/20) not reported before in the Caucasian and Indo–Caucasoid populations, detected in this study. Nine genotypes (15/18, 16/18, 16/21, 17/19, 18/19, 18/21, 19/19, 19/21 and 21/21) which were present in the Caucasian and/or Indo–Caucasoid populations were absent in this study. Our results showed that CBS 31-bp VNTR polymorphism has a distinct genetic difference in allele and genotype frequencies between the European Caucasians, Indo–Caucasoid and Asian populations.

  11. Erastin sensitizes glioblastoma cells to temozolomide by restraining xCT and cystathionine-γ-lyase function.

    Science.gov (United States)

    Chen, Liangyu; Li, Xinxing; Liu, Libo; Yu, Bo; Xue, Yixue; Liu, Yunhui

    2015-03-01

    Glioblastoma multiforme (GBM) is one of the most common encephalic malignant tumors. Due to a high recurrence rate and a lack of effective treatments, the average survival rate remains low. Temozolomide (TMZ), a class of alkylating agent, is widely used as a first-line therapeutic drug during the adjuvant treatment for GBM patients. However, most patients exhibit a palpable resistance to TMZ treatment. Additionally, the underlying mechanism remains to be clarified. In this study, glutathione (GSH) and reactive oxygen species (ROS) levels were found to be closely associated with the sensitivity of GBM cells to TMZ. We also found that TMZ markedly induced xCT, the subunit of glutamate/cystine transporter system xc- expression, which together with the GSH synthesis was increased while the TMZ-inducible ROS level was decreased in GBM cells. In addition, the cystathionine γ-lyase (CTH) acivity, a key enzyme in the transsulfuration pathway was enhanced by TMZ, which insured a cysteine supply and GSH synthesis in a compensatory manner when xCT was blocked. Thus, the individual inhibition of xCT by siRNA and a pharmacological inhibitor (sulfasalazine) only partially inhibited GSH synthesis and moderately enhanced the GBM cell sensitivity to TMZ. However, the TMZ‑induced cytotoxicity was markedly increased along with a marked decrease in GSH levels as result of co-treatment with erastin, which inhibited cysteine uptake from xCT transporter and suppressed CTH activity, leading to impaired transformation from methionine to cysteine. In conclusion, to GBM therapy with a drug combination of TMZ and erastin may be beneficial.

  12. 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...

  13. Cystathionine β-synthase-derived hydrogen sulfide regulates lipopolysaccharide-induced apoptosis of the BRL rat hepatic cell line in vitro.

    Science.gov (United States)

    Yan, Jun; Teng, Feixiang; Chen, Weiwei; Ji, Yinglei; Gu, Zhenyong

    2012-11-01

    Hydrogen sulfide (H(2)S), is a member of the novel family of endogenous gaseous transmitters, termed "gasotransmitters exhibiting diverse physiological activities, and is generated in mammalian tissues mainly by cystathionine β-synthase (CBS), cystathionine γ-lyase (CSE) and 3-mercaptopyruvate sulfurtransferase (3MST) in conjunction with cysteine (aspartate) aminotranferase (CAT). The distributions of these enzymes are species- and tissue-specific. The liver, as the main organ that generates H(2)S in vivo, functions in biotransformation and metabolism. However, the liver is vulnerable to damage from internal and external factors, including inflammatory mediators, drugs and poisons. The present study evaluated the endogenous CBS-H(2)S synthesis regulating lipopolysaccharide (LPS)-induced apoptosis of hepatic cells. The rat hepatic cell line, BRL, was incubated with LPS for various time periods to establish a cell-damage model. Incubation with LPS resulted in a significant increase in CBS expression and H(2)S production. It also stimulated apoptosis and decreased the mitochondrial membrane potential. Pretreatment with the CBS inhibitor aminooxyacetic acid (AOAA) or CBS small interfering RNA (siRNA) decreased LPS-enhanced H(2)S production. Notably, apoptosis increased for a short period and then decreased gradually, while the mitochondrial membrane potential demonstrated the opposite trend. These results showed that endogenous CBS-H(2)S synthesis demonstrated early anti-apoptotic activity and subsequent pro-apoptotic activity in LPS-induced apoptosis. These results suggest a new approach for developing novel drugs for this condition.

  14. Folding and activity of mutant cystathionine β-synthase depends on the position and nature of the purification tag: characterization of the R266K CBS mutant.

    Science.gov (United States)

    Majtan, Tomas; Kraus, Jan P

    2012-04-01

    Cystathionine β-synthase (CBS), a heme-containing pyridoxal-5-phosphate (PLP)-dependent enzyme, catalyzes the condensation of serine and homocysteine to yield cystathionine. Missense mutations in CBS, the most common cause of homocystinuria, often result in misfolded proteins. Arginine 266, where the pathogenic missense mutation R266K was identified, appears to be involved in the communication between heme and the PLP-containing catalytic center. Here, we assessed the effect of a short affinity tag (6xHis) compared to a bulky fusion partner (glutathione S-transferase - GST) on CBS wild type (WT) and R266K mutant enzyme properties. While WT CBS was successfully expressed either in conjunction with a GST or with a 6xHis tag, the mutant R266K CBS had no activity, did not form native tetramers and did not respond to chemical chaperone treatment when expressed with a GST fusion partner. Interestingly, expression of R266K CBS constructs with a 6xHis tag at either end yielded active enzymes. The purified, predominantly tetrameric, R266K CBS with a C-terminal 6xHis tag had ∼82% of the activity of a corresponding WT CBS construct. Results from thermal pre-treatment of the enzyme and the denaturation profile of R266K suggests a lower thermal stability of the mutant enzyme compared to WT, presumably due to a disturbed heme environment. Copyright © 2012 Elsevier Inc. All rights reserved.

  15. Statins upregulate cystathionine γ-lyase transcription and H2S generation via activating Akt signaling in macrophage.

    Science.gov (United States)

    Xu, Yuan; Du, Hua-Ping; Li, Jiaojiao; Xu, Ran; Wang, Ya-Li; You, Shou-Jiang; Liu, Huihui; Wang, Fen; Cao, Yong-Jun; Liu, Chun-Feng; Hu, Li-Fang

    2014-09-01

    Hydrogen sulfide (H2S), the third gaseous transmitter, is implicated in various pathophysiologic processes. In the cardiovascular system, H2S exerts effects of cardioprotection, vascular tone regulation, and atherogenesis inhibition. Recent studies demonstrated that atorvastatin, the inhibitor of 3-hydroxyl-3-methyl coenzyme A reductase, affected H2S formation in kidney and other organs. However, the underlying mechanisms are not fully understood. In this study, we examined the effects of three different statins (fluvastatin, atorvastatin and pravastatin) on H2S formation in raw264.7 macrophages. There was a remarkable rise in H2S level in fluvastatin- and atorvastatin-stimulated macrophages, while pravastatin failed to show any significant effect on it. Moreover, fluvastatin and atorvastatin enhanced the mRNA and protein expression of cystathionine γ-lyase (CSE) in dose- and time-dependent manners. Fluvastatin also markedly enhanced the CSE activity. However, fluvastatin did not alter the mRNA or protein expression of another H2S-producing enzyme 3-mercaptopyruvate sulfurtransferase. Blockade of CSE with its inhibitor dl-propargylglycine (PAG) or siRNA markedly reduced the H2S level in fluvastatin-stimulated macrophages. In addition, fluvastatin elevated Akt phosphorylation, which occurred as early as 15 min after treatment, peaked at 1h, and lasted at least 3h. Both PI3K inhibitor LY294002 (10 μM) and Akt inhibitor perifosine (10μM) were able to reverse the increases of CSE mRNA and H2S production in fluvastatin-stimulated macrophages. Last, we showed that fluvastatin reduced the mRNA levels of pro-inflammatory molecules such as IL-1β and MCP-1 in LPS-treated macrophages, which were completely reversed by CSE inhibitor PAG. Taken together, the findings demonstrate that statins may up-regulate CSE expression/activity and subsequently elevate H2S generation by activating Akt signaling pathway and also imply that CSE-H2S pathway plays a critical role in the anti

  16. Adenosine kinase deficiency with neurodevelopemental delay and recurrent hepatic dysfunction: A case report

    Science.gov (United States)

    Shakiba, Marjan; Mahjoub, Fatemeh; Fazilaty, Hassan; Rezagholizadeh, Fereshteh; Shakiba, Arghavan; Ziadlou, Maryam; Gahl, William A.; Behnam, Babak

    2016-01-01

    Hypermethioninemia may be benign, present as a nonspecific sign of nongenetic conditions such as liver failure and prematurity, or a severe, progressive inborn error of metabolism. Genetic causes of hypermethioninemia include mitochondrial depletion syndromes caused by mutations in the MPV17 and DGUOK genes and deficiencies of cystathionine β-synthase, methionine adenosyltransferase types I and III, glycine N-methyltransferase, S-adenosylhomocysteine hydrolase, citrin, fumarylacetoacetate hydrolase, and adenosine kinase. Here we present a 3-year old girl with a history of poor feeding, irritability, respiratory infections, cholestasis, congenital heart disease, neurodevelopmental delay, hypotonia, sparse hair, facial dysmorphisms, liver dysfunction, severe hypermethioninemia and mild homocystinemia. Genetic analysis of the adenosine kinase (ADK) gene revealed a previously unreported variant (c.479–480 GA>TG) resulting in a stop codon (p.E160X) in ADK. A methionine-restricted diet normalized the liver function test results and improved her hypotonia. PMID:27500280

  17. 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 ...

  18. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... at highest risk for iron-deficiency anemia. Outlook Doctors usually can successfully treat iron-deficiency anemia. Treatment ... poor skin tone, dizziness, and depression. After her doctor diagnosed her with iron-deficiency anemia, Susan got ...

  19. Cystathionine γ-lyase

    Directory of Open Access Journals (Sweden)

    Halina Jurkowska

    2014-01-01

    Full Text Available γ-Cystathionase (CTH, EC: 4.4.1.1, an enzyme widely distributed in the world of prokaryotic and eukaryotic organisms, catalyzes the formation and transformations of sulfane sulfur-containing compounds and plays a pivotal role in the L-cysteine desulfuration pathway. Human, tetrameric CTH is composed of two dimers and each monomer binds pyridoxal phosphate (PLP. The gene, located on the short arm of chromosome 1, consists of 13 exons and 12 introns. As a result of alternative splicing, three isoforms of human CTH arise. Analysis of genetic variations of the CTH encoding gene showed a large number of polymorphisms. A decrease of the expression of CTH entails a drop in the level of cysteine , glutathione (GSH, taurine and hydrogen sulfide (H2S in the cells and, more importantly, leads to cystathioninuria. H2S, endogenously formed by CTH, affects the vasodilation and regulation of blood pressure. CTH knockout mice have decreased levels of H2S, hypertension, and reduced capacity for vascular endothelium relaxation. Overexpression of the gene encoding CTH in the cells leads to increased production of H2S. H2S plays a role in protection of neurons against oxidative stress, and stimulates an increase in γ-glutamylcysteine synthetase and thereby an increase in the level of GSH. Sulfurtransferases, including CTH, can locally prevent oxidative stress due to reversible oxidation of – SH groups in the presence of increased levels of reactive oxygen species, and reduction in the presence of GSH and/or reduced thioredoxin.

  20. [Cystathionine γ-lyase].

    Science.gov (United States)

    Jurkowska, Halina; Kaczor-Kamińska, Marta; Bronowicka-Adamska, Patrycja; Wróbel, Maria

    2014-01-01

    γ-Cystathionase (CTH, EC: 4.4.1.1), an enzyme widely distributed in the world of prokaryotic and eukaryotic organisms, catalyzes the formation and transformations of sulfane sulfur-containing compounds and plays a pivotal role in the L-cysteine desulfuration pathway. Human, tetrameric CTH is composed of two dimers and each monomer binds pyridoxal phosphate (PLP). The gene, located on the short arm of chromosome 1, consists of 13 exons and 12 introns. As a result of alternative splicing, three isoforms of human CTH arise. Analysis of genetic variations of the CTH encoding gene showed a large number of polymorphisms. A decrease of the expression of CTH entails a drop in the level of cysteine , glutathione (GSH), taurine and hydrogen sulfide (H2S) in the cells and, more importantly, leads to cystathioninuria. H2S, endogenously formed by CTH, affects the vasodilation and regulation of blood pressure. CTH knockout mice have decreased levels of H2S, hypertension, and reduced capacity for vascular endothelium relaxation. Overexpression of the gene encoding CTH in the cells leads to increased production of H2S. H2S plays a role in protection of neurons against oxidative stress, and stimulates an increase in γ-glutamylcysteine synthetase and thereby an increase in the level of GSH. Sulfurtransferases, including CTH, can locally prevent oxidative stress due to reversible oxidation of - SH groups in the presence of increased levels of reactive oxygen species, and reduction in the presence of GSH and/or reduced thioredoxin.

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

    Directory of Open Access Journals (Sweden)

    Yi-Qun Liu

    2014-01-01

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

  2. The metabolomic responses of Caenorhabditis elegans to cadmium are largely independent of metallothionein status, but dominated by changes in cystathionine and phytochelatins.

    Science.gov (United States)

    Hughes, Samantha L; Bundy, Jacob G; Want, Elizabeth J; Kille, Peter; Stürzenbaum, Stephen R

    2009-07-01

    Cadmium is a widely distributed toxic environmental pollutant. Using proton NMR spectroscopy and UPLC-MS, we obtained metabolic profiles from the model organism Caenorhabditis elegans exposed to sublethal concentrations of cadmium. Neither in the presence nor absence of cadmium did the metallothionein status (single or double mtl knockouts) markedly modulate the metabolic profile. However, independent of strain, cadmium exposure resulted in a decrease in cystathionine concentrations and an increase in the nonribosomally synthesized peptides phytochelatin-2 and phytochelatin-3. This suggests that a primary response to low levels of cadmium is the differential regulation of the C. elegans trans-sulfuration pathway, which channels the flux from methionine through cysteine into phytochelatin synthesis. These results were backed up by the finding that phytochelatin synthase mutants (pcs-1) were at least an order of magnitude more sensitive to cadmium than single or double metallothionein mutants. However, an additive sensitivity toward cadmium was observed in the mtl-1; mtl-2; pcs-1 triple mutant.

  3. Expression, crystallization and preliminary X-ray crystallographic analysis of XometC, a cystathionine γ-lyase-like protein from Xanthomonas oryzae pv. oryzae

    Energy Technology Data Exchange (ETDEWEB)

    Ngo, Phuong-Thuy Ho; Kim, Jin-Kwang [Department of Advanced Technology Fusion, Konkuk University, Hwayang-dong, Gwangjin-gu, Seoul 143-701 (Korea, Republic of); Kim, Hyesoon [Major in Life Science, College of Natural Sciences, Sangmyung University, 7 Hongji-dong, Jongno-gu, Seoul 110-743 (Korea, Republic of); Jung, Junho [Department of Advanced Technology Fusion, Konkuk University, Hwayang-dong, Gwangjin-gu, Seoul 143-701 (Korea, Republic of); Ahn, Yeh-Jin [Major in Life Science, College of Natural Sciences, Sangmyung University, 7 Hongji-dong, Jongno-gu, Seoul 110-743 (Korea, Republic of); Kim, Jeong-Gu; Lee, Byoung-Moo [Microbial Genetics Division, National Institute of Agricultural Biotechnology (NIAB), Rural Development Administration (RDA), Suwon 441-707 (Korea, Republic of); Kang, Hee-Wan, E-mail: kanghw2@hknu.ac.kr [Graduate School of Biotechnology and Information, Hankyong National University, Ansung 456-749 (Korea, Republic of); Kang, Lin-Woo, E-mail: kanghw2@hknu.ac.kr [Department of Advanced Technology Fusion, Konkuk University, Hwayang-dong, Gwangjin-gu, Seoul 143-701 (Korea, Republic of)

    2008-08-01

    XometC, a cystathionine γ-lyase-like protein from X. oryzae pv. oryzae and an antibacterial drug-target protein against bacterial blight, was cloned, purified and crystallized. Preliminary X-ray crystallographic analysis of XometC crystals was carried out. Xanthomonas oryzae pv. oryzae (Xoo) causes bacterial blight of rice (Oryza sativa L.), one of the most devastating diseases of rice in most rice-growing countries. XometC, a cystathionine γ-lyase (CGL) like protein that is an antibacterial drug-target protein against Xoo, was cloned, expressed, purified and crystallized. CGL catalyzes the second step in the reverse-transsulfuration pathway, which is essential for the metabolic interconversion of the sulfur-containing amino acids cysteine and methionine. Crystals of two different shapes, plate-shaped and pyramid-shaped, diffracted to 2.9 and 3.2 Å resolution and belonged to the primitive orthogonal space group P2{sub 1}2{sub 1}2{sub 1} and the tetragonal space group P4{sub 1} (or P4{sub 3}), with unit-cell parameters a = 73.0, b = 144.9, c = 152.3 Å and a = b = 78.2, c = 300.7 Å, respectively. For the P2{sub 1}2{sub 1}2{sub 1} crystals, three or four monomers exist in the asymmetric unit with a corresponding V{sub M} of 3.02 or 2.26 Å{sup 3} Da{sup −1} and a solvent content of 59.3 or 45.7%. For the P4{sub 1} (or P4{sub 3}) crystals, four or five monomers exist in the asymmetric unit with a corresponding V{sub M} of 2.59 or 2.09 Å{sup 3} Da{sup −1} and a solvent content of 52.5 or 40.6%.

  4. Estrogen Replacement Therapy in Ovariectomized Nonpregnant Ewes Stimulates Uterine Artery Hydrogen Sulfide Biosynthesis by Selectively Up-Regulating Cystathionine β-Synthase Expression.

    Science.gov (United States)

    Lechuga, Thomas J; Zhang, Hong-hai; Sheibani, Lili; Karim, Muntarin; Jia, Jason; Magness, Ronald R; Rosenfeld, Charles R; Chen, Dong-bao

    2015-06-01

    Estrogens dramatically dilate numerous vascular beds with the greatest response in the uterus. Endogenous hydrogen sulfide (H2S) is a potent vasodilator and proangiogenic second messenger, which is synthesized from L-cysteine by cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE). We hypothesized that estrogen replacement therapy (ERT) selectively stimulates H2S biosynthesis in uterine artery (UA) and other systemic arteries. Intact and endothelium-denuded UA, mesenteric artery (MA), and carotid artery (CA) were obtained from ovariectomized nonpregnant ewes (n = 5/group) receiving vehicle or estradiol-17β replacement therapy (ERT). Total RNA and protein were extracted for measuring CBS and CSE, and H2S production was determined by the methylene blue assay. Paraffin-embedded UA rings were used to localize CBS and CSE proteins by immunofluorescence microscopy. ERT significantly stimulated CBS mRNA and protein without altering CSE mRNA or protein in intact and denuded UA. Quantitative immunofluorescence microscopic analyses showed CBS and CSE protein localization in endothelium and smooth muscle and confirmed that ERT stimulated CBS but not CSE protein expression in UA endothelium and smooth muscle. ERT also stimulated CBS, but not CSE, mRNA and protein expression in intact and denuded MA but not CA in ovariectomized ewes. Concomitantly, ERT stimulated UA and MA but not CA H2S production. ERT-stimulated UA H2S production was completely blocked by a specific CBS but not CSE inhibitor. Thus, ERT selectively stimulates UA and MA but not CA H2S biosynthesis by specifically up-regulating CBS expression, implicating a role of H2S in estrogen-induced vasodilation and postmenopausal women's health.

  5. Differential response of methionine metabolism in two grain legumes, soybean and azuki bean, expressing a mutated form of Arabidopsis cystathionine γ-synthase.

    Science.gov (United States)

    Hanafy, Moemen S; Rahman, Shaikh M; Nakamoto, Yumi; Fujiwara, Toru; Naito, Satoshi; Wakasa, Kyo; Ishimoto, Masao

    2013-02-15

    Methionine (Met) is a sulfur-containing amino acid that is essential in mammals and whose low abundance limits the nutritional value of grain legumes. Cystathionine γ-synthase (CGS) catalyzes the first committed step of Met biosynthesis, and the stability of its mRNA is autoregulated by the cytosolic concentration of S-adenosyl-l-methionine (SAM), a direct metabolite of Met. The mto1-1 mutant of Arabidopsis thaliana harbors a mutation in the AtCGS1 gene that renders the mRNA resistant to SAM-dependent degradation and therefore results in the accumulation of free Met to high levels in young leaves. To manipulate Met biosynthesis in soybean and azuki bean, we introduced the AtCGS1 mto1-1 gene into the two grain legumes under the control of a seed-specific glycinin gene promoter. Transgenic seeds of both species accumulated soluble Met to levels at least twice those apparent in control seeds. However, the increase in free Met did not result in an increase in total Met content of the transgenic seeds. In transgenic azuki bean seeds, the amount of cystathionine, the direct product of CGS, was markedly increased whereas the total content of Met was significantly decreased compared with control seeds. Similar changes were not detected in soybean. Our data suggest that the regulation of Met biosynthesis differs between soybean and azuki bean, and that the expression of AtCGS1 mto1-1 differentially affects the metabolic stability of sulfur amino acids and their metabolites in the two grain legumes.

  6. Carnitine Deficiency and Pregnancy

    OpenAIRE

    Anouk de Bruyn; Yves Jacquemyn; Kristof Kinget; François Eyskens

    2015-01-01

    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, su...

  7. [Hydrogen sulfide as a biologically active mediator in the cardiovascular system].

    Science.gov (United States)

    Bełtowski, Jerzy

    2004-07-19

    Recent studies suggest that apart from nitric oxide (NO) and carbon monoxide (CO), hydrogen sulfide (H2S) is another inorganic gaseous mediator in the cardiovascular system. H2S is synthesized from L-cysteine by either cystathionine beta-synthase (CBS) or cystathionin gamma--lyase (CSE), both using pyridoxal 5'-phosphate (vitamin B6) as a cofactor. CBS is the main H2S-producing enzyme in the brain and CSE is involved in H2S formation in the cardiovascular system. H2S induces hypotension in vivo and vasodilation vitro by opening KATP channels in vascular smooth muscle cells. Chronic administration of CSE inhibitor induces arterial hypertension in the rat. In addition, decreased H2S generation has been demonstrated in the vasculature of spontaneously hypertensive rat, in experimental hypertension induced by NO synthase blockade, and in hypoxia-induced pulmonary hypertension, and administration of exogenous H2S donor has significant therapeutic effects in these models. Deficiency of H2S may contribute to atherogenesis in some patients with hyperhomocysteinemia, in whom the metabolism of homocysteine to cysteine and H2S is compromised by vitamin B6 deficiency. Reduced H2S production in the brain was observed in patients with Alzheimer's disease. On the other hand, excess of H2S may lead to mental retardation in patients with Down's syndrome and may be involved in the pathogenesis of hypotension associated with septic shock.

  8. Serotonin and dopamine protect from hypothermia/rewarming damage through the CBS/H2S pathway

    NARCIS (Netherlands)

    Talaei, Fatemeh; Bouma, Hjalmar; Van der Graaf, Adrianus; Strijkstra, Arjen; Schmidt, Martina; Henning, Robert

    2011-01-01

    Biogenic amines have been demonstrated to protect cells from apoptotic cell death. Herein we show for the first time that serotonin and dopamine increase H2S production by the endogenous enzyme cystathionine-beta-synthase (CBS) and protect cells against hypothermia/rewarming induced reactive oxygen

  9. Familial lipoprotein lipase deficiency

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/000408.htm Familial lipoprotein lipase deficiency To use the sharing features on this page, please enable JavaScript. Familial lipoprotein lipase deficiency is a group of rare genetic ...

  10. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... This Content: NEXT >> Featured Video Living With and Managing Iron-Deficiency Anemia 05/18/2011 This video— ... treatment. For more information about living with and managing iron-deficiency anemia, go to the Health Topics ...

  11. 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 ... of the condition. Treatments may include dietary changes, medicines, and surgery. Severe iron-deficiency anemia may require ...

  12. Folate-deficiency anemia

    Science.gov (United States)

    ... medlineplus.gov/ency/article/000551.htm Folate-deficiency anemia To use the sharing features on this page, please enable JavaScript. Folate-deficiency anemia is a decrease in red blood cells (anemia) ...

  13. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... severity of the condition. Treatments may include dietary changes, medicines, and surgery. Severe iron-deficiency anemia may require treatment in a hospital, blood ... With and Managing Iron-Deficiency Anemia 05/18/2011 This video— ...

  14. 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 ... condition. Treatments may include dietary changes, medicines, and surgery. Severe iron-deficiency anemia may require treatment in ...

  15. Iron-Deficiency Anemia

    Medline Plus

    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 ...

  16. 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 ... Google+ SITE INDEX ACCESSIBILITY PRIVACY STATEMENT FOIA NO FEAR ACT OIG CONTACT US National Institutes of Health ...

  17. 酵母胱硫醚β-合成酶的表达及酶活鉴定%Expression and Characterization of Yeast Cystathionine β-Synthase

    Institute of Scientific and Technical Information of China (English)

    王利群; 奚学志; 曹利民; 顾雅萍; 孙培培

    2013-01-01

    将重组质粒pET45b-yCBS转入E.coli BL21中,构建高效表达酵母胱硫醚β-合成酶(yeast cystathionine β-synthase,1)的重组菌.研究诱导时菌体浓度、诱导剂IPTG浓度、诱导时间和温度,以及在培养基中添加不同浓度的山梨醇、葡萄糖、甘油对1表达量的影响.使用Ni2+亲和色谱柱纯化重组蛋白,再经His-Trap脱盐柱脱盐,以茚三酮法检测蛋白活性.结果表明,培养基中添加0.05%的山梨醇,重组菌在37℃培养3h后,添加终浓度为0.1 mmo/L的IPTG于20℃诱导培养15h,可溶性1表达量达到110 mg/L;纯化后比活为1 320 u/mg.%The recombinant vector pET45b-yCBS was constructed and transformed into E.coli BL21 to over-express yeast cystathionine β-synthase (1).The effects of various factors on the protein expression were studied,including strain density,the concentration of the inducer IPTG and inducing temperature and time,as well as the cosubstrates such as sorbitol,glucose and glycerin.The expressed protein was purified by Ni2+ chelating affinity chromatography and desalted by His-Trap desalting column,and its activity was determined with the ninhydrin reaction.The results indicated that the expression level of 1 is the highest when the recombinant strain was induced by 0.1 mmol/L IPTG for 15 h at 20 ℃ after cultured for 3 h at 37 ℃ in the LB medium supplemented with 0.05 % sorbitol.The productivity of the soluble 1 reached 110 mg/L.The specific activity of purified 1 is 1 320 u/mg.

  18. Iron-Deficiency Anemia

    Science.gov (United States)

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

  19. Iron-Deficiency Anemia

    Science.gov (United States)

    ... 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 ...

  20. Iron-Deficiency Anemia

    Medline Plus

    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 ...

  1. Iron-Deficiency Anemia

    Medline Plus

    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 ...

  2. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... Deficiency Anemia? Español Iron-deficiency anemia is a common, easily treated condition that occurs if you don' ... from food. Overview Iron-deficiency anemia is a common type of anemia . The term "anemia" usually refers ...

  3. 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.

  4. Cystathionine-γ-lyase gene silencing with siRNA in monocytes/ macrophages attenuates inflammation in cecal ligation and puncture-induced sepsis in the mouse

    Indian Academy of Sciences (India)

    A Badiei; ST Chambers; RR Gaddam; M Bhatia

    2016-03-01

    Hydrogen sulphide is an endogenous inflammatory mediator produced by cystathionine-γ-lyase (CSE) in macrophages. To determine the role of H2S and macrophages in sepsis, we used small interference RNA (siRNA) to target the CSE gene and investigated its effect in a mouse model of sepsis. Cecal ligation puncture (CLP)-induced sepsis is characterized by increased levels of myeloperoxidase (MPO) activity, morphological changes in liver and pro-inflammatory cytokines and chemokines in the liver and lung. SiRNA treatment attenuated inflammation in the liver and lungs of mice following CLP-induced sepsis. Liver MPO activity increased in CLP-induced sepsis and treatment with siRNA significantly reduced this. Similarly, lung MPO activity increased following induction of sepsis with CLP while siRNA treatment significantly reduced MPO activity. Liver and lung cytokine and chemokine levels in CLP-induced sepsis reduced following treatment with siRNA. These findings show a crucial pro-inflammatory role for H2S synthesized by CSE in macrophages in sepsis and suggest CSE gene silencing with siRNA as a potential therapeutic approach for this condition.

  5. Human cystathionine β-synthase (CBS) contains two classes of binding sites for S-adenosylmethionine (SAM): complex regulation of CBS activity and stability by SAM.

    Science.gov (United States)

    Pey, Angel L; Majtan, Tomas; Sanchez-Ruiz, Jose M; Kraus, Jan P

    2013-01-01

    CBS (cystathionine β-synthase) is a multidomain tetrameric enzyme essential in the regulation of homocysteine metabolism, whose activity is enhanced by the allosteric regulator SAM (S-adenosylmethionine). Missense mutations in CBS are the major cause of inherited HCU (homocystinuria). In the present study we apply a novel approach based on a combination of calorimetric methods, functional assays and kinetic modelling to provide structural and energetic insight into the effects of SAM on the stability and activity of WT (wild-type) CBS and seven HCU-causing mutants. We found two sets of SAM-binding sites in the C-terminal regulatory domain with different structural and energetic features: a high affinity set of two sites, probably involved in kinetic stabilization of the regulatory domain, and a low affinity set of four sites, which are involved in the enzyme activation. We show that the regulatory domain displays a low kinetic stability in WT CBS, which is further decreased in many HCU-causing mutants. We propose that the SAM-induced stabilization may play a key role in modulating steady-state levels of WT and mutant CBS in vivo. Our strategy may be valuable for understanding ligand effects on proteins with a complex architecture and their role in human genetic diseases and for the development of novel pharmacological strategies.

  6. Low sulfide levels and a high degree of cystathionine β-synthase (CBS) activation by S-adenosylmethionine (SAM) in the long-lived naked mole-rat.

    Science.gov (United States)

    Dziegelewska, Maja; Holtze, Susanne; Vole, Christiane; Wachter, Ulrich; Menzel, Uwe; Morhart, Michaela; Groth, Marco; Szafranski, Karol; Sahm, Arne; Sponholz, Christoph; Dammann, Philip; Huse, Klaus; Hildebrandt, Thomas; Platzer, Matthias

    2016-08-01

    Hydrogen sulfide (H2S) is a gaseous signalling molecule involved in many physiological and pathological processes. There is increasing evidence that H2S is implicated in aging and lifespan control in the diet-induced longevity models. However, blood sulfide concentration of naturally long-lived species is not known. Here we measured blood sulfide in the long-lived naked mole-rat and five other mammalian species considerably differing in lifespan and found a negative correlation between blood sulfide and maximum longevity residual. In addition, we show that the naked mole-rat cystathionine β-synthase (CBS), an enzyme whose activity in the liver significantly contributes to systemic sulfide levels, has lower activity in the liver and is activated to a higher degree by S-adenosylmethionine compared to other species. These results add complexity to the understanding of the role of H2S in aging and call for detailed research on naked mole-rat transsulfuration. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  7. Low sulfide levels and a high degree of cystathionine β-synthase (CBS activation by S-adenosylmethionine (SAM in the long-lived naked mole-rat

    Directory of Open Access Journals (Sweden)

    Maja Dziegelewska

    2016-08-01

    Full Text Available Hydrogen sulfide (H2S is a gaseous signalling molecule involved in many physiological and pathological processes. There is increasing evidence that H2S is implicated in aging and lifespan control in the diet-induced longevity models. However, blood sulfide concentration of naturally long-lived species is not known. Here we measured blood sulfide in the long-lived naked mole-rat and five other mammalian species considerably differing in lifespan and found a negative correlation between blood sulfide and maximum longevity residual. In addition, we show that the naked mole-rat cystathionine β-synthase (CBS, an enzyme whose activity in the liver significantly contributes to systemic sulfide levels, has lower activity in the liver and is activated to a higher degree by S-adenosylmethionine compared to other species. These results add complexity to the understanding of the role of H2S in aging and call for detailed research on naked mole-rat transsulfuration.

  8. Potentiation of Hypoxic Pulmonary Vasoconstriction by Hydrogen Sulfide Precursors 3-Mercaptopyruvate and D-Cysteine Is Blocked by the Cystathionine γ Lyase Inhibitor Propargylglycine.

    Science.gov (United States)

    Prieto-Lloret, Jesus; Aaronson, Philip I

    2015-01-01

    Although the gasotransmitter hydrogen sulfide (H(2)S) generally dilates systemic arteries in mammals, it causes constriction of pulmonary arteries. In isolated rat pulmonary arteries, we have shown that the H(2)S precursor cysteine enhances both hypoxic pulmonary vasoconstriction and tension development caused by the agonist prostaglandin F(2α) under normoxic conditions. These effects were blocked by propargylglycine (PAG), a blocker of the enzyme cystathionine γ lyase which metabolises cysteine to sulfide. In the present study, we evaluated whether 3-mercaptopyruvate (3-MP), a sulfide precursor which is thought to give rise to sulfide when it is metabolised by the enzyme mercaptopyruvate sulfurtransferase, also enhanced contraction. Application of 3-MP prior to hypoxic challenge caused a marked enhancement of HPV which was completely blocked by both L- and D,L-PAG (both 1 mM). Cumulative application of 3-1,000 μM 3-MP during an ongoing contraction to PGF(2α) under normoxic conditions also caused a marked increase in tension. Application of D-cysteine (1 mM) also enhanced HPV, and this effect was prevented by both the D-amino acid oxidase inhibitor sodium benzoate (500 μM) and 1 mM L-PAG.

  9. Spontaneous perforation of the small intestine, a novel manifestation of classical homocystinuria in an adult with new cystathionine beta-synthetase gene mutations.

    Science.gov (United States)

    Muacević-Katanec, Diana; Kekez, Tihomir; Fumić, Ksenija; Barić, Ivo; Merkler, Marijan; Jakić-Razumović, Jasminka; Krznarić, Zeljko; Zadro, Renata; Katanec, Davor; Reiner, Zeljko

    2011-03-01

    The clinical picture of classical homocystinuria is diverse. This is the first report of an adult homocystinuric patient with non-traumatic spontaneous small bowel perforation. A 47-year old man presented with abdominal rebound tenderness, hypotension and tachycardia, anemia, and elevated markers of inflammation. Other routine laboratory tests were normal. Abdominal x-ray showed no free air. An emergency laparotomy revealed jejunal perforation in the left upper quadrant. Histologic specimen showed full-thickness nonspecific inflammation of the intestinal wall with granulocytic infiltration, hemorrhage and necrosis. Tuberculosis, actinomycosis and typhus were histologically and clinically excluded. After excluding all known possible causes of perforation, we presumed a causative relationship between homocystinuria and small bowel perforation. It could be hypothesized that connective tissue weakness in homocystinuria is a result of homocysteine interference with recombinant human fibrillin-1 fragments or cross-linking of collagen through permanent degradation of disulfide bridges and lysine amino acid residues in proteins. DNA analysis showed three detectable mutations in the cystathionine beta-synthetase gene, 1278T:c.833T>C, and two new mutations, V372G:c.1133T > G, and D520G:c.1558A > G in the aternatively spliced exon 15.

  10. Inhibition of cystathionine β-synthetase suppresses sodium channel activities of dorsal root ganglion neurons of rats with lumbar disc herniation

    Science.gov (United States)

    Yan, Jun; Hu, Shufen; Zou, Kang; Xu, Min; Wang, Qianliang; Miao, Xiuhua; Yu, Shan Ping; Xu, Guang-Yin

    2016-01-01

    The pathogenesis of pain in lumbar disc herniation (LDH) remains poorly understood. We have recently demonstrated that voltage-gated sodium channels (VGSCs) in dorsal root ganglion (DRG) neurons were sensitized in a rat model of LDH. However, the detailed molecular mechanism for sensitization of VGSCs remains largely unknown. This study was designed to examine roles of the endogenous hydrogen sulfide synthesizing enzyme cystathionine β-synthetase (CBS) in sensitization of VGSCs in a previously validated rat model of LDH. Here we showed that inhibition of CBS activity by O-(Carboxymethyl) hydroxylamine hemihydrochloride (AOAA) significantly attenuated pain hypersensitivity in LDH rats. Administration of AOAA also reduced neuronal hyperexcitability, suppressed the sodium current density, and right-shifted the V1/2 of the inactivation curve, of hindpaw innervating DRG neurons, which is retrogradely labeled by DiI. In vitro incubation of AOAA did not alter the excitability of acutely isolated DRG neurons. Furthermore, CBS was colocalized with NaV1.7 and NaV1.8 in hindpaw-innervating DRG neurons. Treatment of AOAA markedly suppressed expression of NaV1.7 and NaV1.8 in DRGs of LDH rats. These data suggest that targeting the CBS-H2S signaling at the DRG level might represent a novel therapeutic strategy for chronic pain relief in patients with LDH. PMID:27905525

  11. Purification and Characterization of Cystathionine (beta)-Lyase from Lactococcus lactis subsp. cremoris B78 and Its Possible Role in Flavor Development in Cheese.

    Science.gov (United States)

    Alting, A C; Engels, W; van Schalkwijk, S; Exterkate, F A

    1995-11-01

    An enzyme that degrades sulfur-containing amino acids was purified from Lactococcus lactis subsp. cremoris B78; this strain was isolated from a mixed-strain, mesophilic starter culture used for the production of Gouda cheese. The enzyme has features of a cystathionine (beta)-lyase (EC 4.4.1.8), a pyridoxal-5(prm1)-phosphate-dependent enzyme involved in the biosynthesis of methionine and catalyzing an (alpha),(beta)-elimination reaction. It is able to catalyze an (alpha),(gamma)-elimination reaction as well, which in the case of methionine, results in the production of methanethiol, a putative precursor of important flavor compounds in cheese. The native enzyme has a molecular mass of approximately 130 to 165 kDa and consists of four identical subunits of 35 to 40 kDa. The enzyme is relatively thermostable and has a pH optimum for activity around 8.0; it is still active under cheese-ripening conditions, viz., pH 5.2 to 5.4 and 4% (wt/vol) NaCl. A possible essential role of the enzyme in flavor development in cheese is suggested.

  12. The role of surface electrostatics on the stability, function and regulation of human cystathionine β-synthase, a complex multidomain and oligomeric protein.

    Science.gov (United States)

    Pey, Angel L; Majtan, Tomas; Kraus, Jan P

    2014-09-01

    Human cystathionine β-synthase (hCBS) is a key enzyme of sulfur amino acid metabolism, controlling the commitment of homocysteine to the transsulfuration pathway and antioxidant defense. Mutations in hCBS cause inherited homocystinuria (HCU), a rare inborn error of metabolism characterized by accumulation of toxic homocysteine in blood and urine. hCBS is a complex multidomain and oligomeric protein whose activity and stability are independently regulated by the binding of S-adenosyl-methionine (SAM) to two different types of sites at its C-terminal regulatory domain. Here we study the role of surface electrostatics on the complex regulation and stability of hCBS using biophysical and biochemical procedures. We show that the kinetic stability of the catalytic and regulatory domains is significantly affected by the modulation of surface electrostatics through noticeable structural and energetic changes along their denaturation pathways. We also show that surface electrostatics strongly affect SAM binding properties to those sites responsible for either enzyme activation or kinetic stabilization. Our results provide new insight into the regulation of hCBS activity and stability in vivo with implications for understanding HCU as a conformational disease. We also lend experimental support to the role of electrostatic interactions in the recently proposed binding modes of SAM leading to hCBS activation and kinetic stabilization.

  13. 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.

  14. Metabolomic analysis reveals extended metabolic consequences of marginal vitamin B-6 deficiency in healthy human subjects.

    Directory of Open Access Journals (Sweden)

    Jesse F Gregory

    Full Text Available Marginal deficiency of vitamin B-6 is common among segments of the population worldwide. Because pyridoxal 5'-phosphate (PLP serves as a coenzyme in the metabolism of amino acids, carbohydrates, organic acids, and neurotransmitters, as well as in aspects of one-carbon metabolism, vitamin B-6 deficiency could have many effects. Healthy men and women (age: 20-40 y; n = 23 were fed a 2-day controlled, nutritionally adequate diet followed by a 28-day low-vitamin B-6 diet (<0.5 mg/d to induce marginal deficiency, as reflected by a decline of plasma PLP from 52.6±14.1 (mean ± SD to 21.5±4.6 nmol/L (P<0.0001 and increased cystathionine from 131±65 to 199±56 nmol/L (P<0.001. Fasting plasma samples obtained before and after vitamin B6 restriction were analyzed by (1H-NMR with and without filtration and by targeted quantitative analysis by mass spectrometry (MS. Multilevel partial least squares-discriminant analysis and S-plots of NMR spectra showed that NMR is effective in classifying samples according to vitamin B-6 status and identified discriminating features. NMR spectral features of selected metabolites indicated that vitamin B-6 restriction significantly increased the ratios of glutamine/glutamate and 2-oxoglutarate/glutamate (P<0.001 and tended to increase concentrations of acetate, pyruvate, and trimethylamine-N-oxide (adjusted P<0.05. Tandem MS showed significantly greater plasma proline after vitamin B-6 restriction (adjusted P<0.05, but there were no effects on the profile of 14 other amino acids and 45 acylcarnitines. These findings demonstrate that marginal vitamin B-6 deficiency has widespread metabolic perturbations and illustrate the utility of metabolomics in evaluating complex effects of altered vitamin B-6 intake.

  15. New insights into the metabolism of organomercury compounds: mercury-containing cysteine S-conjugates are substrates of human glutamine transaminase K and potent inactivators of cystathionine γ-lyase.

    Science.gov (United States)

    Bridges, Christy C; Krasnikov, Boris F; Joshee, Lucy; Pinto, John T; Hallen, André; Li, Jianyong; Zalups, Rudolfs K; Cooper, Arthur J L

    2012-01-01

    Anthropogenic practices and recycling in the environment through natural processes result in release of potentially harmful levels of mercury into the biosphere. Mercury, especially organic forms, accumulates in the food chain. Mercury reacts readily with sulfur-containing compounds and often exists as a thiol S-conjugate, such as the l-cysteine (Cys)-S-conjugate of methylmercury (CH(3)Hg-S-Cys) or inorganic mercury (Cys-S-Hg-S-Cys). These S-conjugates are structurally similar to l-methionine and l-cystine/l-cystathionine, respectively. Bovine and rat glutamine transaminase K (GTK) catalyze transamination of sulfur-containing amino acids. Recombinant human GTK (rhGTK) has a relatively open catalytic active site, and we report here that this enzyme, like the rat and bovine enzymes, can also utilize sulfur-containing l-amino acids, including l-methionine, l-cystine, and l-cystathionine as substrates. The current study extends this list to include mercuric S-conjugates, and shows that CH(3)Hg-S-Cys and Cys-S-Hg-S-Cys are substrates and reversible inhibitors of rhGTK. The homocysteine S-conjugates, Hcy-S-Hg-S-Hcy and CH(3)Hg-S-Hcy, are also inhibitors. Finally, we show that HgCl(2), CH(3)Hg-S-Cys and Cys-S-Hg-S-Cys are potent irreversible inhibitors of rat cystathionine γ-lyase. The present study broadens our knowledge of the biochemistry of mercury compounds by showing that Cys S-conjugates of mercury interact with enzymes that catalyze transformations of biologically important sulfur-containing amino acids.

  16. A functional variant in the cystathionine β-synthase gene promoter significantly reduces congenital heart disease susceptibility in a Han Chinese population

    Institute of Scientific and Technical Information of China (English)

    Jian-Yuan Zhao; Xue-Yan Yang; Kai-Hu Shi; Shu-Na Sun; Jia Hou; Zhi-Zhou Ye; Jue Wang

    2013-01-01

    Homocysteine is an independent risk factor for various cardiovascular diseases.There are two ways to remove homocysteine from embryonic cardiac cells:remethylation to form methionine or transsulfuration to form cysteine.Cystathionine β-synthase (CBS) catalyzes the first step of homocysteine transsulfuration as a rate-limiting enzyme.In this study,we identified a functional variant-4673C>G (rs2850144) in the CBS gene promoter region that significantly reduces the susceptibility to congenital heart disease (CHD) in a Han Chinese population consisting of 2 340 CHD patients and 2 270 controls.Individuals carrying the heterozygous CG and homozygous GG genotypes had a 15% (odds ratio (OR) =0.85,95% confidence interval (CI) =0.75-0.96,P =0.011) and 40% (OR =0.60,95% CI =0.49-0.73,P =1.78 × 10-7) reduced risk to develop CHD than the wild-type CC genotype carriers in the combined samples,respectively.Additional stratified analyses demonstrated that CBS-4673C>G is significantly related to septation defects and conotruncal defects.In vivo detection of CBS mRNA levels in human cardiac tissues and in vitro luciferase assays consistently showed that the minor G allele significantly increased CBS transcription.A functional analysis revealed that both the attenuated transcription suppressor SP1 binding affinity and the CBS promoter hypomethylation specifically linked with the minor G allele contributed to the remarkably upregulated CBS expression.Consequently,the carriers with genetically increased CBS expression would benefit from the protection due to the low homocysteine levels maintained by CBS in certain cells during the critical heart development stages.These results shed light on unexpected role of CBS and highlight the importance of homocysteine removal in cardiac development.

  17. Hydrogen sulfide (H{sub 2}S)/cystathionine γ-lyase (CSE) pathway contributes to the proliferation of hepatoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Pan, Yan; Ye, Shuang; Yuan, Dexiao; Zhang, Jianghong; Bai, Yang; Shao, Chunlin, E-mail: clshao@shmu.edu.cn

    2014-05-15

    Highlights: • Inhibition of H{sub 2}S/CSE pathway strongly stimulates cellular apoptosis. • Inhibition of H{sub 2}S/CSE pathway suppresses cell growth by blocking EGFR pathway. • H{sub 2}S/CSE pathway is critical for maintaining the proliferation of hepatoma cells. - Abstract: Hydrogen sulfide (H{sub 2}S)/cystathionine γ-lyase (CSE) pathway has been demonstrated to play vital roles in physiology and pathophysiology. However, its role in tumor cell proliferation remains largely unclear. Here we found that CSE over-expressed in hepatoma HepG2 and PLC/PRF/5 cells. Inhibition of endogenous H{sub 2}S/CSE pathway drastically decreased the proliferation of HepG2 and PLC/PRF/5 cells, and it also enhanced ROS production and mitochondrial disruption, pronounced DNA damage and increased apoptosis. Moreover, this increase of apoptosis was associated with the activation of p53 and p21 accompanied by a decreased ratio of Bcl-2/Bax and up-regulation of phosphorylated c-Jun N-terminal kinase (JNK) and caspase-3 activity. In addition, the negative regulation of cell proliferation by inhibition of H{sub 2}S/CSE system correlated with the blockage of cell mitogenic and survival signal transduction of epidermal growth factor receptor (EGFR) via down-regulating the extracellular-signal-regulated kinase 1/2 (ERK1/2) activation. These results demonstrate that H{sub 2}S/CSE and its downstream pathway contribute to the proliferation of hepatoma cells, and inhibition of this pathway strongly suppress the excessive growth of hepatoma cells by stimulating mitochondrial apoptosis and suppressing cell growth signal transduction.

  18. Upregulation of cystathionine beta-synthetase expression by nuclear factor-kappa B activation contributes to visceral hypersensitivity in adult rats with neonatal maternal deprivation

    Directory of Open Access Journals (Sweden)

    Li Lin

    2012-12-01

    Full Text Available Abstract Background Irritable bowel syndrome (IBS is characterized by chronic visceral hyperalgesia (CVH that manifested with persistent or recurrent abdominal pain and altered bowel movement. However, the pathogenesis of the CVH remains unknown. The aim of this study was to investigate roles of endogenous hydrogen sulfide (H2S producing enzyme cystathionine beta-synthetase (CBS and p65 nuclear factor-kappa B subunits in CVH. Results CVH was induced by neonatal maternal deprivation (NMD in male rats on postnatal days 2–15 and behavioral experiments were conducted at the age of 7–15 weeks. NMD significantly increased expression of CBS in colon-innervating DRGs from the 7th to 12th week. This change in CBS express is well correlated with the time course of enhanced visceromoter responses to colorectal distention (CRD, an indicator of visceral pain. Administration of AOAA, an inhibitor of CBS, produced a dose-dependent antinociceptive effect on NMD rats while it had no effect on age-matched healthy control rats. AOAA also reversed the enhanced neuronal excitability seen in colon-innervating DRGs. Application of NaHS, a donor of H2S, increased excitability of colon-innervating DRG neurons acutely dissociated from healthy control rats. Intrathecal injection of NaHS produced an acute visceral hyperalgesia. In addition, the content of p65 in nucleus was remarkably higher in NMD rats than that in age-matched controls. Intrathecal administration of PDTC, an inhibitor of p65, markedly reduced expression of CBS and attenuated nociceptive responses to CRD. Conclusion The present results suggested that upregulation of CBS expression, which is mediated by activation of p65, contributes to NMD-induced CVH. This pathway might be a potential target for relieving CVH in patients with IBS.

  19. The endogenous hydrogen sulfide producing enzyme cystathionine-β synthase contributes to visceral hypersensitivity in a rat model of irritable bowel syndrome

    Directory of Open Access Journals (Sweden)

    Chen Jiande DZ

    2009-08-01

    Full Text Available Abstract Background The pathogenesis of visceral hypersensitivity, a characteristic pathophysiological feature of irritable bowel syndrome (IBS, remains elusive. Recent studies suggest a role for hydrogen sulfide (H2S in pain signaling but this has not been well studied in visceral models of hyperalgesia. We therefore determined the role for the endogenous H2S producing enzyme cystathionine-β-synthetase (CBS in a validated rat model of IBS-like chronic visceral hyperalgesia (CVH. CVH was induced by colonic injection of 0.5% acetic acid (AA in 10-day-old rats and experiments were performed at 8–10 weeks of age. Dorsal root ganglion (DRG neurons innervating the colon were labeled by injection of DiI (1,1'-dioleyl-3,3,3',3-tetramethylindocarbocyanine methanesulfonate into the colon wall. Results In rat DRG, CBS-immunoreactivity was observed in approximately 85% of predominantly small- and medium-sized neurons. Colon specific DRG neurons revealed by retrograde labeling DiI were all CBS-positive. CBS-positive colon neurons co-expressed TRPV1 or P2X3 receptors. Western blotting analysis showed that CBS expression was significantly increased in colon DRGs 8 weeks after neonatal AA-treatment. Furthermore, the CBS inhibitor hydroxylamine markedly attenuated the abdominal withdrawal reflex scores in response to colorectal distention in rats with CVH. By contrast, the H2S donor NaHS significantly enhanced the frequency of action potentials of colon specific DRG neurons evoked by 2 times rheobase electrical stimulation. Conclusion Our results suggest that upregulation of CBS expression in colonic DRG neurons and H2S signaling may play an important role in developing CVH, thus identifying a specific neurobiological target for the treatment of CVH in functional bowel syndromes.

  20. 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

  1. 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 ...

  2. 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 ...

  3. 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)....

  4. Growth Hormone Deficiency

    Directory of Open Access Journals (Sweden)

    Ömer Tarım

    2010-05-01

    Full Text Available Growth hormone deficiency is the most promising entity in terms of response to therapy among the treatable causes of growth retardation. It may be due to genetic or acquired causes. It may be isolated or a part of multiple hormone deficiencies. Diagnostic criteria and therefore treatment indications are still disputed. (Journal of Current Pediatrics 2010; 8: 36-8

  5. 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

  6. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... periods. By following her treatment plan and making smart lifestyle choices, Susan continues to feel better and see the benefits of treatment. For more information about living with and managing iron-deficiency anemia, go to the Health Topics Iron-Deficiency Anemia article. Updated: March 26, ...

  7. Iron induced nickel deficiency

    Science.gov (United States)

    It is increasingly apparent that economic loss due to nickel (Ni) deficiency likely occurs in horticultural and agronomic crops. While most soils contain sufficient Ni to meet crop requirements, situations of Ni deficiency can arise due to antagonistic interactions with other metals. This study asse...

  8. 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

  9. Deficiently Extremal Gorenstein Algebras

    Indian Academy of Sciences (India)

    Pavinder Singh

    2011-08-01

    The aim of this article is to study the homological properties of deficiently extremal Gorenstein algebras. We prove that if / is an odd deficiently extremal Gorenstein algebra with pure minimal free resolution, then the codimension of / must be odd. As an application, the structure of pure minimal free resolution of a nearly extremal Gorenstein algebra is obtained.

  10. 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 ...

  11. 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

  12. [Hyperhomocysteinemia: atherothrombosis and neurotoxicity].

    Science.gov (United States)

    Fridman, O

    1999-01-01

    The positive correlation existing between hyperhomocyst(e)inemia [HH(e)] and vascular disease has firmly been established through data derived from numerous epidemiological and experimental observations. Clinical data corroborate that homocysteine (Hcy) is an independent risk factor for coronary, cerebral and peripheral arterial occlusive disease or peripheral venous thrombosis. Hcy is a sulfhydryl-containing amino acid that is formed by the demethylation of methionine. It is normally catalyzed to cystathionine by cystathionine beta-synthase a pyridoxal phosphate-dependent enzyme. Hcy is also remethylated to methionine by 5-methyltetrahydrofolate-Hcy methyltransferase (methionine synthase), a vitamin B12 dependent enzyme and by betaine-Hcy methyltransferase. Nutritional status such as vitamin B12, or vitamin B6, or folate deficiencies and genetic defects such as cystathionine beta-synthase or methylene-tetrahydrofolate reductase may contribute to increasing plasma homocysteine levels. The pathogenesis of Hcy-induced vascular damage may be multifactorial, including direct Hcy damage to the endothelium, stimulation of proliferation of smooth muscle cells, enhanced low-density lipoprotein peroxidation, increase of platelet aggregation, and effects on the coagulation system. Besides adverse effects on the endothelium and vessel wall, Hcy exert a toxic action on neuronal cells trough the stimulation of N-methyl-D-aspartate (NMDA) receptors. Under these conditions, neuronal damage derives from excessive calcium influx and reactive oxygen generation. This mechanism may contribute to the cognitive changes and markedly increased risk of cerebrovascular disease in children and young adults with homocystunuria. Moreover, during stroke, in hiperhomocysteinemic patients, disruption of the blood-brain barrier results in exposure of the brain to near plasma levels of Hcy. The brain is exposed to 15-50 microM H(e). Thus, the neurotoxicity of Hcy acting through the overstimulation

  13. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... Events Spokespeople Email Alerts E-Newsletters About NHLBI Organization NHLBI Director Budget, Planning, & Legislative Advisory Committees Jobs ... severity of the condition. Treatments may include dietary changes, medicines, and surgery. Severe iron-deficiency anemia may ...

  14. Factor II deficiency

    Science.gov (United States)

    ... if one or more of these factors are missing or are not functioning like they should. Factor II is one such coagulation factor. Factor II deficiency runs in families (inherited) and is very rare. Both parents must ...

  15. Factor VII deficiency

    Science.gov (United States)

    ... if one or more of these factors are missing or are not functioning like they should. Factor VII is one such coagulation factor. Factor VII deficiency runs in families (inherited) and is very rare. Both parents must ...

  16. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... of Intramural Research Research Resources Research Meeting Summaries Technology Transfer Clinical Trials What Are Clinical Trials? Children & ... of the condition. Treatments may include dietary changes, medicines, and surgery. Severe iron-deficiency anemia may require ...

  17. 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 ...

  18. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... CAUSES WHO IS AT RISK SIGNS & SYMPTOMS DIAGNOSIS TREATMENTS PREVENTION LIVING WITH CLINICAL TRIALS LINKS Related Topics ... Doctors usually can successfully treat iron-deficiency anemia. Treatment will depend on the cause and severity of ...

  19. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... deficiency anemia may require treatment in a hospital, blood transfusions , iron injections, or intravenous iron therapy. Rate This ... video—presented by the National Heart, Lung, and Blood Institute, part of the National ...

  20. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... such as tiredness, poor skin tone, dizziness, and depression. After her doctor diagnosed her with iron-deficiency ... to stop her monthly periods. By following her treatment plan and making smart lifestyle choices, Susan continues ...

  1. 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 ...

  2. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... chest pain, and other symptoms. Severe iron-deficiency anemia can lead to heart problems, infections, problems with growth and development in children, and other complications. Infants and young children and ...

  3. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... Events Spokespeople Email Alerts E-Newsletters About NHLBI Organization NHLBI Director Budget, Planning, & Legislative Advisory Committees Jobs ... food. Overview Iron-deficiency anemia is a common type of anemia . The term "anemia" usually refers to ...

  4. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... Events Spokespeople Email Alerts E-Newsletters About NHLBI Organization NHLBI Director Budget, Planning, & Legislative Advisory Committees Jobs ... the body. Iron-deficiency anemia usually develops over time if your body doesn't have enough iron ...

  5. Sleep Deprivation and Deficiency

    Science.gov (United States)

    ... page from the NHLBI on Twitter. What Are Sleep Deprivation and Deficiency? Sleep deprivation (DEP-rih-VA- ... Rate This Content: NEXT >> Updated: June 7, 2017 Sleep Infographic Sleep Disorders & Insufficient Sleep: Improving Health through ...

  6. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... chest pain, and other symptoms. Severe iron-deficiency anemia can lead to heart problems, infections, problems with growth and development in children, and other complications. Infants and young children and ...

  7. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... CAUSES WHO IS AT RISK SIGNS & SYMPTOMS DIAGNOSIS TREATMENTS PREVENTION LIVING WITH CLINICAL TRIALS LINKS Related Topics ... Doctors usually can successfully treat iron-deficiency anemia. Treatment will depend on the cause and severity of ...

  8. 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, ...

  9. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... Intramural Research Research Resources Research Meeting Summaries Technology Transfer Clinical Trials What Are Clinical Trials? Children & Clinical ... iron-deficiency anemia may require treatment in a hospital, blood transfusions , iron injections, or intravenous iron therapy. ...

  10. 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 ...

  11. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... of breath, chest pain, and other symptoms. Severe iron-deficiency anemia can lead to heart problems, infections, problems with growth and development in children, and other complications. Infants and young children and ...

  12. 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 ...

  13. “Zipped Synthesis” by Cross-Metathesis Provides a Cystathionine β-Synthase Inhibitor that Attenuates Cellular H2S Levels and Reduces Neuronal Infarction in a Rat Ischemic Stroke Model

    Science.gov (United States)

    2016-01-01

    The gaseous neuromodulator H2S is associated with neuronal cell death pursuant to cerebral ischemia. As cystathionine β-synthase (CBS) is the primary mediator of H2S biogenesis in the brain, it has emerged as a potential target for the treatment of stroke. Herein, a “zipped” approach by alkene cross-metathesis into CBS inhibitor candidate synthesis is demonstrated. The inhibitors are modeled after the pseudo-C2-symmetric CBS product (l,l)-cystathionine. The “zipped” concept means only half of the inhibitor needs be constructed; the two halves are then fused by olefin cross-metathesis. Inhibitor design is also mechanism-based, exploiting the favorable kinetics associated with hydrazine-imine interchange as opposed to the usual imine–imine interchange. It is demonstrated that the most potent “zipped” inhibitor 6S reduces H2S production in SH-SY5Y cells overexpressing CBS, thereby reducing cell death. Most importantly, CBS inhibitor 6S dramatically reduces infarct volume (1 h post-stroke treatment; ∼70% reduction) in a rat transient middle cerebral artery occlusion model for ischemia. PMID:27163055

  14. Iron deficiency anemia

    OpenAIRE

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

    2012-01-01

    Iron is essential to virtually all living organisms and is integral to multiple metabolic functions. 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. Severe iron deficiency is characterized by a microcytic, hypochromic, potentially severe anemia with a variable regenerative response. Iron metabolism and homeostasis will be ...

  15. Proximal Focal Femoral Deficiency

    OpenAIRE

    Vishal Kalia, Vibhuti

    2008-01-01

    Proximal focal femoral deficiency (PFFD) is a developmental disorder of the proximal segment of thefemur and of acetabulum resulting in shortening of the affected limb and impairment of the function. It isa spectrum of congenital osseous anomalies characterized by a deficiency in the structure of the proximalfemur. The diagnosis is often made by radiological evaluation which includes identification and descriptionof PFFD and evaluation of associated limb anomalies by plain radiographs. Contra...

  16. 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...

  17. Vitamin B12 deficiency.

    Science.gov (United States)

    Oh, Robert; Brown, David L

    2003-03-01

    Vitamin B12 (cobalamin) deficiency is a common cause of macrocytic anemia and has been implicated in a spectrum of neuropsychiatric disorders. The role of B12 deficiency in hyperhomocysteinemia and the promotion of atherosclerosis is only now being explored. Diagnosis of vitamin B12 deficiency is typically based on measurement of serum vitamin B12 levels; however, about 50 percent of patients with subclinical disease have normal B12 levels. A more sensitive method of screening for vitamin B12 deficiency is measurement of serum methylmalonic acid and homocysteine levels, which are increased early in vitamin B12 deficiency. Use of the Schilling test for detection of pernicious anemia has been supplanted for the most part by serologic testing for parietal cell and intrinsic factor antibodies. Contrary to prevailing medical practice, studies show that supplementation with oral vitamin B12 is a safe and effective treatment for the B12 deficiency state. Even when intrinsic factor is not present to aid in the absorption of vitamin B12 (pernicious anemia) or in other diseases that affect the usual absorption sites in the terminal ileum, oral therapy remains effective.

  18. Interaction between hydrogen sulfide/cystathionine γ-lyase and carbon monoxide/heme oxygenase pathways in aortic smooth muscle cells

    Institute of Scientific and Technical Information of China (English)

    Hong-fang JIN; Jun-bao DU; Xiao-hui LI; Yan-fei WANG; Yin-fang LIANG; Chao-shu TANG

    2006-01-01

    Aim: To investigate the interaction between hydrogen sulfide (H2S)/cystathionine γ-lyase (CSE) and carbon monoxide (CO)/heme oxygenase (HO) pathways in aortic smooth muscle cells (ASMC). Methods: The ASMCs were divided into the following groups: (1) the control group; (2) the zinc protoporphyrin (ZnPP) 20 (μmol/L group; (3) the propargylglycine (PPG) 2 mmol/L, 4 mmol/L and 10 mmol/L groups; and (4) the sodium hydrosulfide (NaHS) 1×10-5 mol/L, 1×10-4 mol/L and 1×10-3 mol/L groups. Each of the groups was further divided into 6 h, 12 h, 18 h and 24 h subgroups. The CO level, represented by carboxyhemoglobin (HbCO) content was measured using a spectrophotometric method and H2S content was detected by a sensitive electrode method. CSE and HO-1 expressions were detected by Western blotting. Results: The H2S content in the medium and CSE expression by ASMC were markedly increased by ZnPP compared with the control group. HbCO content in the medium and HO-1 expression by the ASMC started strengthening following 24 h treatment with PPG at 2 mmol/L, but were further strengthened following 18 h and 24 h treatment with PPG at 4 mmol/L compared with the controls (P<0.01). PPG at 10 mmol/L increased the HbCO level in the medium following 18 h treatment and increased HO-1 expression by the ASMC following 12 h treatment. Moreover, NaHS at 1×10-5 mol/L and 1×10-4 mol/L decreased the HbCO level in the medium and HO-1 expression by the ASMC after 6 h and 12 h treatment, while NaHS at 1×10-3 mol/L decreased them at all time points of the treatments. Conclusion: The results suggested that endogenous CO/HO and H2S/CSE pathways inhibited each other in ASMC under physiological conditions.

  19. Arecoline improves vascular endothelial function in high fructose-fed rats via increasing cystathionine-Ylyase expression and activating KATp channels

    Institute of Scientific and Technical Information of China (English)

    Hong-yan LING; Guang WANG; Wei ZHANG; Xing LI; Shou-hong ZHOU; Bi HU

    2012-01-01

    Aim:To investigate the effect of arecoline,a major component of betel nut,on vascular endothelial function in high fructose-fed rats and the potential mechanisms underlying the effect.Methods:Male Wistar rats were fed a high-fructose or control diet for 16 weeks.At the beginning of week 13,the rats were injected ip with low (0.5 mg·kg 1·d-1),medi u m (1.0 mg·kg1·d-1) or high (5.0 mg·kg 1·d 1) doses of arecoline for 4 weeks.At the termination of the treatments,blood was collected,fasting blood glucose (FBG) and serum insulin (FSI) levels were measured,and insulin sensitivity index (ISI) was calculated.The thoracic aortas were isolated and aortic rings were prepared for studying ACh-induced endothelium-dependent vasorelaxation (EDVR).The mRNA and protein expression of cystathionine-y-lyase (CSE) in the thoracic aortas was analyzed using RTPCR and Western blot analysis,respectively.Results:In high fructose-fed rats,the levels of FBG and FSI were remarkably increased,whereas the ISI and the mRNA and protein expression of CSE were significantly decreased.ACh-induced EDVR in the aortic rings from high fructose-fed rats was remarkably reduced.These changes were reversed by treatment with high dose arecoline.Pretreatment of the aortic rings rings from high fructose-fed rats with the CSE inhibitor propargylglycine (10 mmol/L) orthe ATP-sensitive potassium (KATP) channel blocker glibenclamide (10 mmol/L) abolished the restoration of ACh-induced EDVR by high dose arecoline.On the contrary,treatment with high dose arecoline significantly impaired ACh-induced EDVR in the aortic rings from control rats,and pretreatment with propargylglycine or glibenclamide did not cause further changes.Conclusion:Arecoline treatment improves ACh-induced EDVR in high fructose-fed rats,and the potential mechanism of action might be associated with increase of CSE expression and activation of KATP channels by arecoline.

  20. Arecoline improves vascular endothelial function in high fructose-fed rats via increasing cystathionine-γ-lyase expression and activating KATP channels

    Science.gov (United States)

    Ling, Hong-yan; Wang, Guang; Zhang, Wei; Li, Xing; Zhou, Shou-hong; Hu, Bi

    2012-01-01

    Aim: To investigate the effect of arecoline, a major component of betel nut, on vascular endothelial function in high fructose-fed rats and the potential mechanisms underlying the effect. Methods: Male Wistar rats were fed a high-fructose or control diet for 16 weeks. At the beginning of week 13, the rats were injected ip with low (0.5 mg·kg−1·d−1), medium (1.0 mg·kg−1·d−1) or high (5.0 mg·kg−1·d−1) doses of arecoline for 4 weeks. At the termination of the treatments, blood was collected, fasting blood glucose (FBG) and serum insulin (FSI) levels were measured, and insulin sensitivity index (ISI) was calculated. The thoracic aortas were isolated and aortic rings were prepared for studying ACh-induced endothelium-dependent vasorelaxation (EDVR). The mRNA and protein expression of cystathionine-γ-lyase (CSE) in the thoracic aortas was analyzed using RT-PCR and Western blot analysis, respectively. Results: In high fructose-fed rats, the levels of FBG and FSI were remarkably increased, whereas the ISI and the mRNA and protein expression of CSE were significantly decreased. ACh-induced EDVR in the aortic rings from high fructose-fed rats was remarkably reduced. These changes were reversed by treatment with high dose arecoline. Pretreatment of the aortic rings rings from high fructose-fed rats with the CSE inhibitor propargylglycine (10 mmol/L) or the ATP-sensitive potassium (KATP) channel blocker glibenclamide (10 mmol/L) abolished the restoration of ACh-induced EDVR by high dose arecoline. On the contrary, treatment with high dose arecoline significantly impaired ACh-induced EDVR in the aortic rings from control rats, and pretreatment with propargylglycine or glibenclamide did not cause further changes. Conclusion: Arecoline treatment improves ACh-induced EDVR in high fructose-fed rats, and the potential mechanism of action might be associated with increase of CSE expression and activation of KATP channels by arecoline. PMID:22820911

  1. Arecoline improves vascular endothelial function in high fructose-fed rats via increasing cystathionine-γ-lyase expression and activating K(ATP) channels.

    Science.gov (United States)

    Ling, Hong-yan; Wang, Guang; Zhang, Wei; Li, Xing; Zhou, Shou-hong; Hu, Bi

    2012-08-01

    To investigate the effect of arecoline, a major component of betel nut, on vascular endothelial function in high fructose-fed rats and the potential mechanisms underlying the effect. Male Wistar rats were fed a high-fructose or control diet for 16 weeks. At the beginning of week 13, the rats were injected ip with low (0.5 mg·kg(-1)·d(-1)), medium (1.0 mg·kg(-1)·d(-1)) or high (5.0 mg·kg(-1)·d(-1)) doses of arecoline for 4 weeks. At the termination of the treatments, blood was collected, fasting blood glucose (FBG) and serum insulin (FSI) levels were measured, and insulin sensitivity index (ISI) was calculated. The thoracic aortas were isolated and aortic rings were prepared for studying ACh-induced endothelium-dependent vasorelaxation (EDVR). The mRNA and protein expression of cystathionine-γ-lyase (CSE) in the thoracic aortas was analyzed using RT-PCR and Western blot analysis, respectively. In high fructose-fed rats, the levels of FBG and FSI were remarkably increased, whereas the ISI and the mRNA and protein expression of CSE were significantly decreased. ACh-induced EDVR in the aortic rings from high fructose-fed rats was remarkably reduced. These changes were reversed by treatment with high dose arecoline. Pretreatment of the aortic rings rings from high fructose-fed rats with the CSE inhibitor propargylglycine (10 mmol/L) or the ATP-sensitive potassium (K(ATP)) channel blocker glibenclamide (10 mmol/L) abolished the restoration of ACh-induced EDVR by high dose arecoline. On the contrary, treatment with high dose arecoline significantly impaired ACh-induced EDVR in the aortic rings from control rats, and pretreatment with propargylglycine or glibenclamide did not cause further changes. Arecoline treatment improves ACh-induced EDVR in high fructose-fed rats, and the potential mechanism of action might be associated with increase of CSE expression and activation of K(ATP) channels by arecoline.

  2. Iron deficiency anaemia.

    Science.gov (United States)

    Lopez, Anthony; Cacoub, Patrice; Macdougall, Iain C; Peyrin-Biroulet, Laurent

    2016-02-27

    Anaemia affects roughly a third of the world's population; half the cases are due to iron deficiency. It is a major and global public health problem that affects maternal and child mortality, physical performance, and referral to health-care professionals. Children aged 0-5 years, women of childbearing age, and pregnant women are particularly at risk. Several chronic diseases are frequently associated with iron deficiency anaemia--notably chronic kidney disease, chronic heart failure, cancer, and inflammatory bowel disease. Measurement of serum ferritin, transferrin saturation, serum soluble transferrin receptors, and the serum soluble transferrin receptors-ferritin index are more accurate than classic red cell indices in the diagnosis of iron deficiency anaemia. In addition to the search for and treatment of the cause of iron deficiency, treatment strategies encompass prevention, including food fortification and iron supplementation. Oral iron is usually recommended as first-line therapy, but the most recent intravenous iron formulations, which have been available for nearly a decade, seem to replenish iron stores safely and effectively. Hepcidin has a key role in iron homoeostasis and could be a future diagnostic and therapeutic target. In this Seminar, we discuss the clinical presentation, epidemiology, pathophysiology, diagnosis, and acute management of iron deficiency anaemia, and outstanding research questions for treatment.

  3. [Vitamin deficiencies and hypervitaminosis].

    Science.gov (United States)

    Mino, M

    1999-10-01

    There have recently been very few deficiencies with respect to fat soluble and water soluble vitamins in Japan All-trans-retinoic acid as induction or maintenance treatment improves disease free and overall survival against acute promyelocytic leukemia. In the isolated vitamin E deficiencies gene mutation has been cleared for alpha-tocopherol transferprotein. Recently, a relation of nutritional vitamin K intake and senile osteoporosis in women was epidemiologically demonstrated on a prospective study. Thiamin was yet noticed as development of deficiency in alcoholism, while the importance of supplemental folic acid during pregnancy has become especially clear in light of studies showing that folic acid supplements reduce the risk of neural tube defects in the fetus. With respect to hypervitaminosis, the Council for Responsible Nutrition (CRN), USA, has established safe intakes by identifying the NOAEL (No Observed Adverse Effect Level) and LOAEL (Lowest Observed Adverse Effect Level). Summaries of NOAEL and LOAEL for individual vitamins were shown.

  4. 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.

  5. 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 chil......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...

  6. 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 iodine-deficien

  7. Factor V deficiency

    Science.gov (United States)

    ... When certain blood clotting factors are low or missing, your blood does not clot properly. Factor V deficiency is rare. It may be caused by: A defective Factor V gene passed down through families (inherited) An antibody that interferes with normal Factor ...

  8. Alpha1-antitrypsin deficiency

    DEFF Research Database (Denmark)

    Stolk, Jan; Seersholm, Niels; Kalsheker, Noor

    2006-01-01

    biennially to exchange views and research findings. The fourth biennial meeting was held in Copenhagen, Denmark, on 2-3 June 2005. This review covers the wide range of AAT deficiency-related topics that were addressed encompassing advances in genetic characterization, risk factor identification, clinical...... epidemiology, inflammatory and signalling processes, therapeutic advances, and lung imaging techniques....

  9. 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...

  10. 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 ...

  11. 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 iodine-deficien

  12. 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...

  13. 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...

  14. Diagnosing oceanic nutrient deficiency

    Science.gov (United States)

    Moore, C. Mark

    2016-11-01

    The supply of a range of nutrient elements to surface waters is an important driver of oceanic production and the subsequent linked cycling of the nutrients and carbon. Relative deficiencies of different nutrients with respect to biological requirements, within both surface and internal water masses, can be both a key indicator and driver of the potential for these nutrients to become limiting for the production of new organic material in the upper ocean. The availability of high-quality, full-depth and global-scale datasets on the concentrations of a wide range of both macro- and micro-nutrients produced through the international GEOTRACES programme provides the potential for estimation of multi-element deficiencies at unprecedented scales. Resultant coherent large-scale patterns in diagnosed deficiency can be linked to the interacting physical-chemical-biological processes which drive upper ocean nutrient biogeochemistry. Calculations of ranked deficiencies across multiple elements further highlight important remaining uncertainties in the stoichiometric plasticity of nutrient ratios within oceanic microbial systems and caveats with regards to linkages to upper ocean nutrient limitation. This article is part of the themed issue 'Biological and climatic impacts of ocean trace element chemistry'.

  15. Manganese deficiency in plants

    DEFF Research Database (Denmark)

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

    2016-01-01

    Manganese (Mn) is an essential plant micronutrient with an indispensable function as a catalyst in the oxygen-evolving complex (OEC) of photosystem II (PSII). Even so, Mn deficiency frequently occurs without visual leaf symptoms, thereby masking the distribution and dimension of the problem...

  16. 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 ...

  17. Newborn screening for remethylation disorders and vitamin B12 deficiency-evaluation of new strategies in cohorts from Qatar and Germany.

    Science.gov (United States)

    Gramer, Gwendolyn; Abdoh, Ghassan; Ben-Omran, Tawfeg; Shahbeck, Noora; Ali, Rehab; Mahmoud, Laila; Fang-Hoffmann, Junmin; Hoffmann, Georg F; Al Rifai, Hilal; Okun, Jürgen G

    2017-04-01

    Newborn screening is a precondition for early diagnosis and successful treatment of remethylation disorders and classical homocystinuria (cystathionine-ß-synthase deficiency). Newborn screening for classical homocystinuria using total homocysteine measurement in dried blood spots has been very successfully performed for many years for newborns from Qatar. A new optimized newborn screening strategy for remethylation disorders and homocystinuria was developed and evaluated for newborns from Qatar using total homocysteine measurement as first-tier and methionine, methionine-phenylalanine-ratio and propionylcarnitine as second-tiers. Proposed cut-offs were also retrospectively evaluated in newborn screening samples of 12 patients with remethylation disorders and vitamin B12 deficiency from Qatar and Germany. Over a 12 months period, the proposed strategy led to a decrease in the recall rate in homocysteine screening for Qatar from 1.09% to 0.68%, while allowing for additional systematic inclusion of remethylation disorders and vitamin B12 deficiency into the screening panel for Qatar. In the evaluated period the applied strategy would have detected all patients with classical homocystinuria identified by the previous strategy and in addition 5 children with maternal nutritional vitamin B12 deficiency and one patient with an isolated remethylation disorder. Additional retrospective evaluation of newborn screening samples of 12 patients from Germany and Qatar with remethlyation disorders or vitamin B12 deficiency showed that all of these patients would have been detected by the cut-offs used in the proposed new strategy. In addition, an adapted strategy for Germany using methionine, methionine-phenylalanine-ratio and propionylcarnitine as first-tier, and homocysteine as a second-tier test was also positively evaluated retrospectively. The proposed strategy for samples from Qatar allows inclusion of remethylation disorders and vitamin B12 deficiency in the screening

  18. Effect of S-adenosyl-L-methionine (SAM), an allosteric activator of cystathionine-β-synthase (CBS) on colorectal cancer cell proliferation and bioenergetics in vitro.

    Science.gov (United States)

    Módis, Katalin; Coletta, Ciro; Asimakopoulou, Antonia; Szczesny, Bartosz; Chao, Celia; Papapetropoulos, Andreas; Hellmich, Mark R; Szabo, Csaba

    2014-09-15

    Recent data show that colon cancer cells selectively overexpress cystathionine-β-synthase (CBS), which produces hydrogen sulfide (H2S), to maintain cellular bioenergetics, support tumor growth and stimulate angiogenesis and vasorelaxation in the tumor microenvironment. The purpose of the current study was to investigate the effect of the allosteric CBS activator S-adenosyl-L-methionine (SAM) on the proliferation and bioenergetics of the CBS-expressing colon cancer cell line HCT116. The non-transformed, non-tumorigenic colon epithelial cell line NCM356 was used as control. For assessment of cell proliferation, the xCELLigence system was used. Bioenergetic function was measured by Extracellular Flux Analysis. Experiments using human recombinant CBS or HCT116 homogenates complemented the cell-based studies. SAM markedly enhanced CBS-mediated H2S production in vitro, especially when a combination of cysteine and homocysteine was used as substrates. Addition of SAM (0.1-3 mM) to HCT116 cells induced a concentration-dependent increase H2S production. SAM exerted time- and concentration-dependent modulatory effects on cell proliferation. At 0.1-1 mM SAM increased HCT116 proliferation between 0 and 12 h, while the highest SAM concentration (3 mM) inhibited proliferation. Over a longer time period (12-24 h), only the lowest concentration of SAM used (0.1 mM) stimulated cell proliferation; higher SAM concentrations produced a concentration-dependent inhibition. The short-term stimulatory effects of SAM were attenuated by the CBS inhibitor aminooxyacetic acid (AOAA) or by stable silencing of CBS. In contrast, the inhibitory effects of SAM on cell proliferation was unaffected by CBS inhibition or CBS silencing. In contrast to HCT116 cells, the lower rate of proliferation of the low-CBS expressor NCM356 cells was unaffected by SAM. Short-term (1 h) exposure of HCT116 cells to SAM induced a concentration-dependent increase in oxygen consumption and bioenergetic function at 0

  19. Genetics Home Reference: carbonic anhydrase VA deficiency

    Science.gov (United States)

    ... hyperammonemia due to carbonic anhydrase VA deficiency hyperammonemic encephalopathy due to carbonic anhydrase VA deficiency mitochondrial carbonic anhydrase va deficiency Related Information How are ...

  20. Glucose-6-phosphate dehydrogenase deficiency

    Science.gov (United States)

    ... 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 in which ...

  1. Cobalamin deficiency, hyperhomocysteinemia, and dementia

    National Research Council Canada - National Science Library

    Werder, Steven F

    2010-01-01

    ...) What is to be expected from treatment? (7) How is B12 deficiency treated? On January 31st, 2009, a Medline search was performed revealing 1,627 citations related to cobalamin deficiency, hyperhomocysteinemia, and dementia...

  2. Growth Hormone Deficiency in Children

    Science.gov (United States)

    Fact Sheet Growth Defici H e o n r 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 ...

  3. 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

  4. [Selective immunoglobulin A deficiency].

    Science.gov (United States)

    Binek, Alicja; Jarosz-Chobot, Przemysława

    2012-01-01

    Immunoglobulin class A is the main protein of the mucosal immune system. Selective immunoglobulin A deficiency (sIgAD) is the most common primary immunodeficiency in Caucasians. sIGAD is strongly associated with the certain major histocompatibility complex region. Most individuals with sIgAD are asymptomatic and identified coincidentally. However, some patients may present with recurrent infections, allergic disorders and autoimmune manifestations. Several autoimmune diseases, such as systemic lupus erythematosus, diabetes mellitus type 1, Graves disease and celiac disease, are associated with an increased prevalence of sIgAD. Screening for sIgAD in coeliac disease is essential. Patients need treatment of associated diseases. It is also known that IgA deficiency may progress into a common variable immunodeficiency (CVID). Pathogenesis and molecular mechanism involved in sIgAD should be elucidated in the future.

  5. Isolated sulfite oxidase deficiency.

    Science.gov (United States)

    Relinque, B; Bardallo, L; Granero, M; Jiménez, P J; Luna, S

    2015-03-10

    Sulfite oxidase deficiency is an uncommon metabolic disease. Only few cases of its isolated form have been reported in the literature. We report a case of severe neonatal onset. A newborn baby of 41 weeks gestational age, weighted at birth of 3240 grams and had an Apgar score of 6-10-10. Fifty-three hours after being born, the baby started with seizures that were refractory to antiepileptic treatment. Brain function was monitored using a-EEG. Laboratory and imaging tests were performed. All of them were consistent with sulfite oxidase deficiency. The diagnosis was confirmed by genetic testing. We highlight the importance of this disease as part of the differential diagnosis of seizures during the neonatal period, as well as the importance of the therapeutic support based on dietary restrictions. It's also remarkable the possibility of prenatal diagnosis by quantifying enzyme activity and it's also possible carrying out DNA mutational analysis.

  6. Proximal Focal Femoral Deficiency

    Directory of Open Access Journals (Sweden)

    Vishal Kalia, Vibhuti

    2008-01-01

    Full Text Available Proximal focal femoral deficiency (PFFD is a developmental disorder of the proximal segment of thefemur and of acetabulum resulting in shortening of the affected limb and impairment of the function. It isa spectrum of congenital osseous anomalies characterized by a deficiency in the structure of the proximalfemur. The diagnosis is often made by radiological evaluation which includes identification and descriptionof PFFD and evaluation of associated limb anomalies by plain radiographs. Contrast arthrography orMagnetic Resonance Imaging is indicated when radiological features are questionable and to disclose thepresence and location of the femoral head and any cartilagenous anlage. The disorder is more commonlyunilateral and is apparent at birth. However, bilateral involvement is rarely seen. Therapy of the disorder isdirected towards satisfactory ambulation and specific treatment depending on the severity of dysplasia.

  7. Micronutrient deficiency in children.

    Science.gov (United States)

    Bhan, M K; Sommerfelt, H; Strand, T

    2001-05-01

    Malnutrition increases morbidity and mortality and affects physical growth and development, some of these effects resulting from specific micronutrient deficiencies. While public health efforts must be targeted to improve dietary intakes in children through breast feeding and appropriate complementary feeding, there is a need for additional measures to increase the intake of certain micronutrients. Food-based approaches are regarded as the long-term strategy for improving nutrition, but for certain micronutrients, supplementation, be it to the general population or to high risk groups or as an adjunct to treatment must also be considered. Our understanding of the prevalence and consequences of iron, vitamin A and iodine deficiency in children and pregnant women has advanced considerably while there is still a need to generate more knowledge pertaining to many other micronutrients, including zinc, selenium and many of the B-vitamins. For iron and vitamin A, the challenge is to improve the delivery to target populations. For disease prevention and growth promotion, the need to deliver safe but effective amounts of micronutrients such as zinc to children and women of fertile age can be determined only after data on deficiency prevalence becomes available and the studies on mortality reduction following supplementation are completed. Individual or multiple micronutrients must be used as an adjunct to treatment of common infectious diseases and malnutrition only if the gains are substantial and the safety window sufficiently wide. The available data for zinc are promising with regard to the prevention of diarrhea and pneumonia. It should be emphasized that there must be no displacement of important treatment such as ORS in acute diarrhea by adjunct therapy such as zinc. Credible policy making requires description of not only the clinical effects but also the underlying biological mechanisms. As findings of experimental studies are not always feasible to extrapolate to

  8. Orexin deficiency and narcolepsy

    OpenAIRE

    Sakurai, Takeshi

    2013-01-01

    Orexin deficiency results in the sleep disorder narcolepsy in many mammalian species, including mice, dogs, and humans, suggesting that the orexin system is particularly important for normal regulation of sleep/wakefulness states, and especially for maintenance of wakefulness. This review discusses animal models of narcolepsy; the contribution of each orexin receptor subtype to the narcoleptic phenotypes; and the etiology of orexin neuronal death. It also raises the possibility of novel thera...

  9. Damage of hippocampal neurons in rats with chronic alcoholism

    Institute of Scientific and Technical Information of China (English)

    Ailin Du; Hongbo Jiang; Lei Xu; Na An; Hui Liu; Yinsheng Li; Ruiling Zhang

    2014-01-01

    Chronic alcoholism can damage the cytoskeleton and aggravate neurological deifcits. However, the effect of chronic alcoholism on hippocampal neurons remains unclear. In this study, a model of chronic alcoholism was established in rats that were fed with 6%alcohol for 42 days. Endog-enous hydrogen sulifde content and cystathionine-beta-synthase activity in the hippocampus of rats with chronic alcoholism were signiifcantly increased, while F-actin expression was decreased. Hippocampal neurons in rats with chronic alcoholism appeared to have a fuzzy nuclear mem-brane, mitochondrial edema, and ruptured mitochondrial crista. These findings suggest that chronic alcoholism can cause learning and memory decline in rats, which may be associated with the hydrogen sulfide/cystathionine-beta-synthase system, mitochondrial damage and reduced expression of F-actin.

  10. [Iron deficiency, thrombocytosis and thromboembolism].

    Science.gov (United States)

    Evstatiev, Rayko

    2016-10-01

    Iron deficiency, the most common nutritional deficiency worldwide, is often associated with reactive thrombocytosis. Although secondary thrombocytosis is commonly considered to be harmless, there is accumulating evidence that elevated platelet counts, especially in the setting of iron deficiency, can lead to an increased thromboembolic risk in both arterial and venous systems. Here we present the mechanisms of iron deficiency-induced thrombocytosis and summarize its clinical consequences especially in patients with inflammatory bowel diseases, chronic kidney disease or cancer. We hypothesize that iron deficiency is an underestimated thromboembolic risk factor, and that iron replacement therapy can become an effective preventive strategy in a variety of clinical settings.

  11. Iron-Deficiency Anemia (For Parents)

    Science.gov (United States)

    ... TV, Video Games, and the Internet Iron-Deficiency Anemia KidsHealth > For Parents > Iron-Deficiency Anemia Print A ... common nutritional deficiency in children. About Iron-Deficiency Anemia Every red blood cell in the body contains ...

  12. How Is Iron-Deficiency Anemia Treated?

    Science.gov (United States)

    ... the NHLBI on Twitter. How Is Iron-Deficiency Anemia Treated? Treatment for iron-deficiency anemia will depend ... may be advised. Treatments for Severe Iron-Deficiency Anemia Blood Transfusion If your iron-deficiency anemia is ...

  13. Iron-Deficiency Anemia (For Parents)

    Science.gov (United States)

    ... Your 1- to 2-Year-Old Iron-Deficiency Anemia KidsHealth > For Parents > Iron-Deficiency Anemia A A ... common nutritional deficiency in children. About Iron-Deficiency Anemia Every red blood cell in the body contains ...

  14. Phenylalanine hydroxylase deficiency.

    Science.gov (United States)

    Mitchell, John J; Trakadis, Yannis J; Scriver, Charles R

    2011-08-01

    Phenylalanine hydroxylase deficiency is an autosomal recessive disorder that results in intolerance to the dietary intake of the essential amino acid phenylalanine. It occurs in approximately 1:15,000 individuals. Deficiency of this enzyme produces a spectrum of disorders including classic phenylketonuria, mild phenylketonuria, and mild hyperphenylalaninemia. Classic phenylketonuria is caused by a complete or near-complete deficiency of phenylalanine hydroxylase activity and without dietary restriction of phenylalanine most children will develop profound and irreversible intellectual disability. Mild phenylketonuria and mild hyperphenylalaninemia are associated with lower risk of impaired cognitive development in the absence of treatment. Phenylalanine hydroxylase deficiency can be diagnosed by newborn screening based on detection of the presence of hyperphenylalaninemia using the Guthrie microbial inhibition assay or other assays on a blood spot obtained from a heel prick. Since the introduction of newborn screening, the major neurologic consequences of hyperphenylalaninemia have been largely eradicated. Affected individuals can lead normal lives. However, recent data suggest that homeostasis is not fully restored with current therapy. Treated individuals have a higher incidence of neuropsychological problems. The mainstay of treatment for hyperphenylalaninemia involves a low-protein diet and use of a phenylalanine-free medical formula. This treatment must commence as soon as possible after birth and should continue for life. Regular monitoring of plasma phenylalanine and tyrosine concentrations is necessary. Targets of plasma phenylalanine of 120-360 μmol/L (2-6 mg/dL) in the first decade of life are essential for optimal outcome. Phenylalanine targets in adolescence and adulthood are less clear. A significant proportion of patients with phenylketonuria may benefit from adjuvant therapy with 6R-tetrahydrobiopterin stereoisomer. Special consideration must be

  15. Psychiatric manifestations of treatable hereditary metabolic disorders in adults.

    Science.gov (United States)

    Demily, Caroline; Sedel, Frédéric

    2014-01-01

    Detecting psychiatric disorders of secondary origin is a crucial concern for the psychiatrist. But how can this reliably be done among a large number of conditions, most of which have a very low prevalence? Metabolic screening undertaken in a population of subjects with psychosis demonstrated the presence of treatable metabolic disorders in a significant number of cases. The nature of the symptoms that should alert the clinician is also a fundamental issue and is not limited to psychosis. Hereditary metabolic disorders (HMD) are a rare but important cause of psychiatric disorders in adolescents and adults, the signs of which may remain isolated for years before other more specific organic signs appear. HMDs that present purely with psychiatric symptoms are very difficult to diagnose due to low awareness of these rare diseases among psychiatrists. However, it is important to identify HMDs in order to refer patients to specialist centres for appropriate management, disease-specific treatment and possible prevention of irreversible physical and neurological complications. Genetic counselling can also be provided. This review focuses on three HMD categories: acute, treatable HMDs (urea cycle abnormalities, remethylation disorders, acute intermittent porphyria); chronic, treatable HMDs (Wilson's disease, Niemann-Pick disease type C, homocystinuria due to cystathionine beta-synthase deficiency, cerebrotendinous xanthomatosis); and chronic HMDs that are difficult to treat (lysosomal storage diseases, X-linked adrenoleukodystrophy, creatine deficiency syndrome). We also propose an algorithm for the diagnosis of HMDs in patients with psychiatric symptoms.

  16. Iatrogenic nutritional deficiencies.

    Science.gov (United States)

    Young, R C; Blass, J P

    1982-01-01

    This article catalogs the nutritional deficiencies inadvertently introduced by certain treatment regimens. Specifically, the iatrogenic effects on nutrition of surgery, hemodialysis, irradiation, and drugs are reviewed. Nutritional problems are particularly frequent consequences of surgery on the gastrointestinal tract. Gastric surgery can lead to deficiencies of vitamin B12, folate, iron, and thiamine, as well as to metabolic bone disease. The benefits of small bowel bypass are limited by the potentially severe nutritional consequences of this procedure. Following bypass surgery, patients should be monitored for signs of possible nutritional probems such as weight loss, neuropathy, cardiac arrhythmias, loss of stamina, or changes in mental status. Minimal laboratory tests should include hematologic evaluation, B12, folate, iron, albumin, calcium, phosphorus, alkaline phosphatase, transaminases, sodium, potassium, chloride, and carbon dioxide levels. Roentgenologic examination of the bone should also be obtained. Loss of bone substance is a major consequence of many forms of treatment, and dietary supplementation with calcium is warranted. Patients undergoing hemodialysis have shown carnitine and choline deficiencies, potassium depletion, and hypovitaminosis, as well as osteomalacia. Chronic drug use may alter intake, synthesis, absorption, transport, storage, metabolism, or excretion of nutrients. Patients vary markedly in the metabolic effects of drugs, and recommendations for nutrition must be related to age, sex, reproductive status, and genetic endowment. Moreover, the illness being treated can itself alter nutritional requirements and the effect of the treatment on nutrient status. The changes in nutritional levels induced by use of estrogen-containing oral contraceptives (OCs) are obscure; however, the effects on folate matabolism appear to be of less clinical import than previously suggested. Reduction in pyridoxine and serum vitamin B12 levels has been

  17. Treatment of carnitine deficiency.

    Science.gov (United States)

    Winter, S C

    2003-01-01

    Carnitine deficiency is a secondary complication of many inborn errors of metabolism. Pharmacological treatment with carnitine not only corrects the deficiency, it facilitates removal of accumulating toxic acyl intermediates and the generation of mitochondrial free coenzyme A (CoA). The United States Food and Drug Administration (US FDA) approved the use of carnitine for the treatment of inborn errors of metabolism in 1992. This approval was based on retrospective chart analysis of 90 patients, with 18 in the untreated cohort and 72 in the treated cohort. Efficacy was evaluated on the basis of clinical and biochemical findings. Compelling data included increased excretion of disease-specific acylcarnitine derivatives in a dose-response relationship, decreased levels of metabolites in the blood, and improved clinical status with decreased hospitalization frequency, improved growth and significantly lower mortality rates as compared to historical controls. Complications of carnitine treatment were few, with gastrointestinal disturbances and odour being the most frequent. No laboratory or clinical safety issues were identified. Intravenous carnitine preparations were also approved for treatment of secondary carnitine deficiency. Since only 25% of enteral carnitine is absorbed and gastrointestinal tolerance of high doses is poor, parenteral carnitine treatment is an appealing alternative therapeutic approach. In 7 patients treated long term with high-dose weekly to daily venous boluses of parenteral carnitine through a subcutaneous venous port, benefits included decreased frequency of decompensations, improved growth, improved muscle strength and decreased reliance on medical foods with liberalization of protein intake. Port infections were the most troubling complication. Theoretical concerns continue to be voiced that carnitine might result in fatal arrhythmias in patients with long-chain fat metabolism defects. No published clinical studies substantiate these

  18. Phosphorus Deficiency in Ducklins

    Institute of Scientific and Technical Information of China (English)

    CuiHengmin; LuoLingping

    1995-01-01

    20 one-day-old Tianfu ducklings were fed on a natural diet deficient in phosphorus(Ca 0.80%,P 0.366%)for three weeks and examined for signs and lesions.Signs began to appear at the age of one week,and became serous at two weeks.13 ducklings died during the experiment.Morbidity was 100% and mortality was 65%.The affected ducklings mainly showed leg weakness,severe lamencess,deprssion,lack of appetite and stunted growth,The serum alkaline phosphatase activities increased markedly.The serum phosphorus concentration,tibial ash,ash calcium and phosphorus content decreased obviously.At necropsy,maxillae and ribe were soft,and the latter was crooked.Long ones were soft and broke easily.The hypertrophic zone of the growth-plate in the epiphysis of long ones was lengthened and osteoid tissue increased in the metaphyseal spongiosa histopathologically.The above mentioned symptoms and lesions could be prevented by adding phosphorus to the natural deficient diet(up to 0.65%),The relationship between lesions and signs,pathomorphological characterisation and pathogensis were also discussed in this paper.

  19. Glucose-6-phosphatase deficiency

    Directory of Open Access Journals (Sweden)

    Labrune Philippe

    2011-05-01

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

  20. Glucose-6-phosphatase deficiency.

    Science.gov (United States)

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

    2011-05-20

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

  1. Management of Iron Deficiency Anemia

    OpenAIRE

    Jimenez, Kristine; Kulnigg-Dabsch, Stefanie; Gasche, Christoph

    2015-01-01

    Anemia affects one-fourth of the world’s population, and iron deficiency is the predominant cause. Anemia is associated with chronic fatigue, impaired cognitive function, and diminished well-being. Patients with iron deficiency anemia of unknown etiology are frequently referred to a gastroenterologist because in the majority of cases the condition has a gastrointestinal origin. Proper management improves quality of life, alleviates the symptoms of iron deficiency, and reduces the need for blo...

  2. [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.

  3. 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.

  4. Iron deficiency and iron deficiency anemia in women.

    Science.gov (United States)

    Coad, Jane; Pedley, Kevin

    2014-01-01

    Iron deficiency is one of the most common nutritional problems in the world and disproportionately affects women and children. Stages of iron deficiency can be characterized as mild deficiency where iron stores become depleted, marginal deficiency where the production of many iron-dependent proteins is compromised but hemoglobin levels are normal and iron deficiency anemia where synthesis of hemoglobin is decreased and oxygen transport to the tissues is reduced. Iron deficiency anemia is usually assessed by measuring hemoglobin levels but this approach lacks both specificity and sensitivity. Failure to identify and treat earlier stages of iron deficiency is concerning given the neurocognitive implications of iron deficiency without anemia. Most of the daily iron requirement is derived from recycling of senescent erythrocytes by macrophages; only 5-10 % comes from the diet. Iron absorption is affected by inhibitors and enhancers of iron absorption and by the physiological state. Inflammatory conditions, including obesity, can result in iron being retained in the enterocytes and macrophages causing hypoferremia as a strategic defense mechanism to restrict iron availability to pathogens. Premenopausal women usually have low iron status because of iron loss in menstrual blood. Conditions which further increase iron loss, compromise absorption or increase demand, such as frequent blood donation, gastrointestinal lesions, athletic activity and pregnancy, can exceed the capacity of the gastrointestinal tract to upregulate iron absorption. Women of reproductive age are at particularly high risk of iron deficiency and its consequences however there is a controversial argument that evolutionary pressures have resulted in an iron deficient phenotype which protects against infection.

  5. Iodine deficiency in Europe.

    Science.gov (United States)

    Delange, F

    1995-01-18

    Iodine is a trace element present in the human body in minute amounts (15-20 mg in adults, i.e. 0.0285 x 10(-3)% of body weight). The only confirmed function of iodine is to constitute an essential substrate for the synthesis of thyroid hormones, tetraiodothyronine, thyroxine or T4 and triiodothyronine, T3 (1). In thyroxine, iodine is 60% by weight. Thyroid hormones, in turn, play a decisive role in the metabolism of all cells of the organism (2) and in the process of early growth and development of most organs, especially of the brain (3). Brain development in humans occurs from fetal life up to the third postnatal year (4). Consequently, a deficit in iodine and/or in thyroid hormones occurring during this critical period of life will result not only in the slowing down of the metabolic activities of all the cells of the organism but also in irreversible alterations in the development of the brain. The clinical consequence will be mental retardation (5). When the physiological requirements of iodine are not met in a given population, a series of functional and developmental abnormalities occur (Table 1), including thyroid function abnormalities and, when iodine deficiency is severe, endemic goiter and cretinism, endemic mental retardation, decreased fertility rate, increased perinatal death, and infant mortality. These complications, which constitute an hindrance to the development of the affected population, are grouped under the general heading of Iodine Deficiency Disorders, IDD (6). Broad geographic areas exist in which the population is affected by IDD.(ABSTRACT TRUNCATED AT 250 WORDS)

  6. Iron deficiency anemia in children

    OpenAIRE

    Pochinok, T. V.

    2016-01-01

    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.Key words: children, iron deficiency anemia, treatment.

  7. 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 card

  8. 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 of ...

  9. 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.

  10. xCT deficiency aggravates acetaminophen-induced hepatotoxicity under inhibition of the transsulfuration pathway.

    Science.gov (United States)

    Kang, Eun Sil; Lee, Jaeyong; Homma, Takujiro; Kurahashi, Toshihiro; Kobayashi, Sho; Nabeshima, Atsunori; Yamada, Sohsuke; Seo, Han Geuk; Miyata, Satoshi; Sato, Hideyo; Fujii, Junichi

    2017-01-01

    Cystine, an oxidized form of cysteine (Cys), is imported into cells via the protein xCT, which is also associated with the export of glutamate as the counter amino acid. In the current study, we attempted to rationalize roles of xCT in the livers of male mice. While xCT was not expressed in the livers of ordinary mice, it was induced under conditions of glutathione depletion, caused by the administration of acetaminophen (AAP). To differentiate the role between xCT and the transsulfuration pathway on the supply of Cys, we employed an inhibitor of the enzyme cystathionine γ-lyase, propargylglycine (PPG). This inhibitor caused a marked aggravation in AAP-induced hepatic damage and the mortality of the xCT(-/-) mice was increased to a greater extent than that for the xCT(+/+) mice. While a PPG pretreatment had no effect on liver condition or Cys levels, the administration of AAP to the PPG-pretreated mice reduced the levels of Cys as well as glutathione to very low levels in both the xCT(+/+) and xCT(-/-) mice. These findings indicate that the transsulfuration pathway plays a major role in replenishing Cys when glutathione levels are low. Moreover, an ascorbic acid insufficiency, induced by Akr1a ablation, further aggravated the AAP-induced liver damage in the case of the xCT deficiency, indicating that glutathione and ascorbic acid function cooperatively in protecting the liver. In conclusion, while the transsulfuration pathway plays a primary role in supplying Cys to the redox system in the liver, xCT is induced in cases of emergencies, by compensating for Cys supply systems.

  11. Crystal structure of a hypothetical protein, TTHA0829 from Thermus thermophilus HB8, composed of cystathionine-β-synthase (CBS) and aspartate-kinase chorismate-mutase tyrA (ACT) domains.

    Science.gov (United States)

    Nakabayashi, Makoto; Shibata, Naoki; Ishido-Nakai, Emi; Kanagawa, Mayumi; Iio, Yota; Komori, Hirofumi; Ueda, Yasufumi; Nakagawa, Noriko; Kuramitsu, Seiki; Higuchi, Yoshiki

    2016-05-01

    TTHA0829 from Thermus thermophilus HB8 has a molecular mass of 22,754 Da and is composed of 210 amino acid residues. The expression of TTHA0829 is remarkably elevated in the latter half of logarithmic growth phase. TTHA0829 can form either a tetrameric or dimeric structure, and main-chain folding provides an N-terminal cystathionine-β-synthase (CBS) domain and a C-terminal aspartate-kinase chorismate-mutase tyrA (ACT) domain. Both CBS and ACT are regulatory domains to which a small ligand molecule can bind. The CBS domain is found in proteins from organisms belonging to all kingdoms and is observed frequently as two or four tandem copies. This domain is considered as a small intracellular module with a regulatory function and is typically found adjacent to the active (or functional) site of several enzymes and integral membrane proteins. The ACT domain comprises four β-strands and two α-helices in a βαββαβ motif typical of intracellular small molecule binding domains that help control metabolism, solute transport and signal transduction. We discuss the possible role of TTHA0829 based on its structure and expression pattern. The results imply that TTHA0829 acts as a cell-stress sensor or a metabolite acceptor.

  12. Sulfur assimilation and glutathione metabolism under cadmium stress in yeast, protists and plants.

    Science.gov (United States)

    Mendoza-Cózatl, David; Loza-Tavera, Herminia; Hernández-Navarro, Andrea; Moreno-Sánchez, Rafael

    2005-09-01

    Glutathione (gamma-glu-cys-gly; GSH) is usually present at high concentrations in most living cells, being the major reservoir of non-protein reduced sulfur. Because of its unique redox and nucleophilic properties, GSH serves in bio-reductive reactions as an important line of defense against reactive oxygen species, xenobiotics and heavy metals. GSH is synthesized from its constituent amino acids by two ATP-dependent reactions catalyzed by gamma-glutamylcysteine synthetase and glutathione synthetase. In yeast, these enzymes are found in the cytosol, whereas in plants they are located in the cytosol and chloroplast. In protists, their location is not well established. In turn, the sulfur assimilation pathway, which leads to cysteine biosynthesis, involves high and low affinity sulfate transporters, and the enzymes ATP sulfurylase, APS kinase, PAPS reductase or APS reductase, sulfite reductase, serine acetyl transferase, O-acetylserine/O-acetylhomoserine sulfhydrylase and, in some organisms, also cystathionine beta-synthase and cystathionine gamma-lyase. The biochemical and genetic regulation of these pathways is affected by oxidative stress, sulfur deficiency and heavy metal exposure. Cells cope with heavy metal stress using different mechanisms, such as complexation and compartmentation. One of these mechanisms in some yeast, plants and protists is the enhanced synthesis of the heavy metal-chelating molecules GSH and phytochelatins, which are formed from GSH by phytochelatin synthase (PCS) in a heavy metal-dependent reaction; Cd(2+) is the most potent activator of PCS. In this work, we review the biochemical and genetic mechanisms involved in the regulation of sulfate assimilation-reduction and GSH metabolism when yeast, plants and protists are challenged by Cd(2+).

  13. Hydrogen sulfide (H2S) - the third gas of interest for pharmacologists.

    Science.gov (United States)

    Łowicka, Ewelina; Bełtowski, Jerzy

    2007-01-01

    Nitric oxide (NO) and carbon monoxide (CO) synthesized from L-arginine by NO synthase and from heme by heme oxygenase, respectively, are the well-known neurotransmitters and are also involved in the regulation of vascular tone. Recent studies suggest that hydrogen sulfide (H(2)S) is the third gaseous mediator in mammals. H(2)S is synthesized from L-cysteine by either cystathionine beta-synthase (CBS) or cystathionine gamma-lyase (CSE), both using pyridoxal 5'-phosphate (vitamin B(6)) as a cofactor. H(2)S stimulates ATP-sensitive potassium channels (K(ATP)) in the vascular smooth muscle cells, neurons, cardiomyocytes and pancreatic beta-cells. In addition, H(2)S may react with reactive oxygen and/or nitrogen species limiting their toxic effects but also, attenuating their physiological functions, like nitric oxide does. In contrast to NO and CO, H(2)S does not stimulate soluble guanylate cyclase. H(2)S is involved in the regulation of vascular tone, myocardial contractility, neurotransmission, and insulin secretion. H(2)S deficiency was observed in various animal models of arterial and pulmonary hypertension, Alzheimer's disease, gastric mucosal injury and liver cirrhosis. Exogenous H(2)S ameliorates myocardial dysfunction associated with the ischemia/reperfusion injury and reduces the damage of gastric mucosa induced by anti-inflammatory drugs. On the other hand, excessive production of H(2)S may contribute to the pathogenesis of inflammatory diseases, septic shock, cerebral stroke and mental retardation in patients with Down syndrome, and reduction of its production may be of potential therapeutic value in these states.

  14. Genetics Home Reference: protein C deficiency

    Science.gov (United States)

    ... Management Genetic Testing (1 link) Genetic Testing Registry: Thrombophilia, hereditary, due to protein C deficiency, autosomal dominant ... my area? Other Names for This Condition hereditary thrombophilia due to protein C deficiency PROC deficiency Related ...

  15. Genetics Home Reference: glutathione synthetase deficiency

    Science.gov (United States)

    ... Facebook Twitter Home Health Conditions glutathione synthetase deficiency glutathione synthetase deficiency Enable Javascript to view the expand/ ... boxes. Download PDF Open All Close All Description Glutathione synthetase deficiency is a disorder that prevents the ...

  16. Genetics Home Reference: GLUT1 deficiency syndrome

    Science.gov (United States)

    ... Facebook Twitter Home Health Conditions GLUT1 deficiency syndrome GLUT1 deficiency syndrome Enable Javascript to view the expand/ ... boxes. Download PDF Open All Close All Description GLUT1 deficiency syndrome is a disorder affecting the nervous ...

  17. Genetics Home Reference: familial HDL deficiency

    Science.gov (United States)

    ... Genetics Home Health Conditions familial HDL deficiency familial HDL deficiency Enable Javascript to view the expand/collapse ... Download PDF Open All Close All Description Familial HDL deficiency is a condition characterized by low levels ...

  18. Genetics Home Reference: isolated growth hormone deficiency

    Science.gov (United States)

    ... Genetic Testing (4 links) Genetic Testing Registry: Ateleiotic dwarfism Genetic Testing Registry: Autosomal dominant isolated somatotropin deficiency ... in my area? Other Names for This Condition dwarfism, growth hormone deficiency dwarfism, pituitary growth hormone deficiency ...

  19. 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 ...

  20. 胱硫醚γ-裂解酶抑制剂逆转 TNF -α引起的脂肪细胞胰岛素抵抗研究%Study on the inhibitor of cystathionineγ - lyase reverses TNF - α-induced insulin resistance in adipocytes

    Institute of Scientific and Technical Information of China (English)

    吴卫国; 姚伟峰; 黄雌友; 王卓平; 王雯

    2015-01-01

    Objective It is to evaluated the effects of the inhibitor of cystathionine γ - lyase(CSE)on TNF - α - induced insulin resistance in 3T3 - L1 adipocytes. Methods 3T3 - L1 adipocytes were treated with TNF - α for 24 hours to establish insulin resistance adipocytes,with or without being pretreatment with different concentrations of the inhibitor of CSE,DL - pr-opargylglycine(PPG),beta-cyano - L - alanine(BCA),the glucose consumption and uptake and the content of hydrogen sul-fide(H2S)in culture supernatant were observed. Results TNF - α could increase endogenous H2S generation and lead to de-ficiency in insulin-stimulated glucose consumption and uptake in 3T3 - L1 adipocytes. Pretreatment with PPG and BCA prior to the application of TNF - α significantly inhibited H2S synthesis and restored the impaired glucose consumption and uptake by TNF - α respectively. Conclusions Endogenous CSE / H2S system plays an important role in the development of insulin re-sistance in adipocytes,which may be a new direction for the treatment of insulin resistance.%目的:观察胱硫醚γ-裂解酶( CSE)抑制剂对肿瘤坏死因子-α( TNF -α)诱导的脂肪细胞胰岛素抵抗的影响。方法用 TNF -α培养3T3- L1脂肪细胞,建立胰岛素抵抗脂肪细胞模型。经或未经 CSE 抑制剂炔丙基甘氨酸(PPG)和二辛可宁酸(BCA)预处理的脂肪细胞与 TNF -α作用24 h 后,观察脂肪细胞胰岛素刺激的葡萄糖消耗和摄取及硫化氢(H2 S)含量的变化。结果 TNF -α可增加内源性 H2 S 生成并减少3T3- L1脂肪细胞胰岛素刺激的葡萄糖消耗和摄取。BCA 和 PPG 预处理可逆转 TNF -α导致的脂肪细胞胰岛素抵抗。结论内源性 CSE / H2 S 系统在胰岛抵抗的发生发展中发挥着重要作用,可能是治疗胰岛素抵抗的一个新方向。

  1. Iron deficiency and thrombocytosis.

    Science.gov (United States)

    Holbro, A; Volken, T; Buser, A; Sigle, J P; Halter, J P; Passweg, J R; Tichelli, A; Infanti, L

    2017-01-01

    According to many textbooks, iron deficiency (ID) is associated with reactive thrombocytosis. In this study, we aimed to investigate the correlation between serum ferritin levels and platelet counts in a large cohort of healthy blood donors. We included all whole blood and apheresis donors aged 18 years or older with at least one ferritin measurement and one platelet count performed at the same visit between 1996 and 2014. A total of 130 345 blood counts and ferritin measurements obtained from 22 046 healthy donors were analysed. Overall, no correlation between serum ferritin and platelet count was observed (r = -0.03, ρ = 0.04 for males, and r = 0.01, ρ = -0.02 for females, respectively). Associations remained clinically negligible after adjusting for age, time since previous blood donation, number of donations and restricting the analysis to ferritin deciles. In this large, retrospective single-centre study, correlations between low ferritin and platelet count in a large and homogeneous cohort of healthy donors were negligible. Further studies in patients with more severe anaemia and patients with inflammation are warranted. © 2016 International Society of Blood Transfusion.

  2. Iron Deficiency Anemia in Pregnancy.

    Science.gov (United States)

    Breymann, Christian

    2015-10-01

    Anemia is a common problem in obstetrics and perinatal care. Any hemoglobin below 10.5 g/dL can be regarded as true anemia regardless of gestational age. Reasons for anemia in pregnancy are mainly nutritional deficiencies, parasitic and bacterial diseases, and inborn red blood cell disorders such as thalassemias. The main cause of anemia in obstetrics is iron deficiency, which has a worldwide prevalence between estimated 20%-80% and consists of a primarily female population. Stages of iron deficiency are depletion of iron stores, iron-deficient erythropoiesis without anemia, and iron deficiency anemia, the most pronounced form of iron deficiency. Pregnancy anemia can be aggravated by various conditions such as uterine or placental bleedings, gastrointestinal bleedings, and peripartum blood loss. In addition to the general consequences of anemia, there are specific risks during pregnancy for the mother and the fetus such as intrauterine growth retardation, prematurity, feto-placental miss ratio, and higher risk for peripartum blood transfusion. Besides the importance of prophylaxis of iron deficiency, the main therapy options for the treatment of pregnancy anemia are oral iron and intravenous iron preparations.

  3. A novel mechanism of formaldehyde neurotoxicity: inhibition of hydrogen sulfide generation by promoting overproduction of nitric oxide.

    Directory of Open Access Journals (Sweden)

    Xiao-Qing Tang

    Full Text Available BACKGROUND: Formaldehyde (FA induces neurotoxicity by overproduction of intracellular reactive oxygen species (ROS. Increasing studies have shown that hydrogen sulfide (H(2S, an endogenous gastransmitter, protects nerve cells against oxidative stress by its antioxidant effect. It has been shown that overproduction of nitric oxide (NO inhibits the activity of cystathionine-beta-synthase (CBS, the predominant H(2S-generating enzyme in the central nervous system. OBJECTIVE: We hypothesize that FA-caused neurotoxicity involves the deficiency of this endogenous protective antioxidant gas, which results from excessive generation of NO. The aim of this study is to evaluate whether FA disturbs H(2S synthesis in PC12 cells, and whether this disturbance is associated with overproduction of NO. PRINCIPAL FINDINGS: We showed that exposure of PC12 cells to FA causes reduction of viability, inhibition of CBS expression, decrease of endogenous H(2S production, and NO production. CBS silencing deteriorates FA-induced decreases in endogenous H(2S generation, neurotoxicity, and intracellular ROS accumulation in PC12 cells; while ADMA, a specific inhibitor of NOS significantly attenuates FA-induced decreases in endogenous H(2S generation, neurotoxicity, and intracellular ROS accumulation in PC12 cells. CONCLUSION/SIGNIFICANCE: Our data indicate that FA induces neurotoxicity by inhibiting the generation of H(2S through excess of NO and suggest that strategies to manipulate endogenous H(2S could open a suitable novel therapeutic avenue for FA-induced neurotoxicity.

  4. Homocystinuria: A Rare Disorder Presenting as Cerebral Sinovenous Thrombosis

    Directory of Open Access Journals (Sweden)

    Hossein ESLAMIYEH

    2015-06-01

    Full Text Available How to Cite This Article: Eslamiyeh H, Ashrafzadeh F, Akhondian J, Beiraghi Toosi M. Homocystinuria: A Rare Disorder Presenting as Cerebral Sinovenous Thrombosis. Iran J Child Neurol. Spring 2015;9(2:53-57.AbstractObjectiveHomocystinuria is an inborn error of amino acid metabolism caused by cystathionine beta-synthase deficiency that affects methionine metabolism. The clinical features are heterogeneous ranging from mental retardation, ectopia lentis, and osteoporosis to vascular events such as deep vein thrombosis,   sagital sinus thrombosis, and myocardial infarction. Cerebral sinovenous thrombosis (CVST is an unusual disorder in children and requires prompt and accurate management. Some causal factors for thedevelopment of CVST differ between children and adults. The majority of cases with CSVT are found to have an underlying cause for thrombosis like dehydration, infections, prothrombotic and hematologic disorders, malignancy and trauma.Although homocystinuria is usually associated with ischemic strokes, CVST as initial clinical presentation of homocystinuria is rare in children.In this article, we presented a 10-year old boy with seizure, hemiparesis, and ataxia due to CSVT caused by homocystinuria.

  5. A case of homocystinuria due to CBS gene mutations revealed by cerebral venous thrombosis.

    Science.gov (United States)

    Sarov, Mariana; Not, Adeline; de Baulny, Hélène Ogier; Masnou, Pascal; Vahedi, Katayoun; Bousser, Marie-Germaine; Denier, Christian

    2014-01-15

    Homocystinuria caused by cystathionine beta synthase (CBS) deficiency is most often diagnosed in childhood and has a variable expressivity. The most frequent abnormalities include intellectual disability, ectopia lentis, myopia, skeletal abnormalities or thromboembolism. To report a case of homocystinuria unraveled by cerebral venous thrombosis (CVT). A 17 year old female was admitted in our department of neurology for subacute headache and presented seizures in the emergency room. Cerebral imaging revealed CVT. Severe hyperhomocysteinemia was found and led to the diagnosis of homocystinuria due to composite heterozygous mutations in the CBS gene. Further investigations disclosed lens subluxation in association with myopia, mild scoliosis and osteopenia. The patient was treated by heparin followed by warfarin, vitamin therapy and dietary methionine restriction. Total homocysteine and methionine levels became normal in a few weeks and the patient had a complete recovery. In patients with CVT, plasma total homocysteine measurement as part of the etiologic work up may reveal severe hyperhomocysteinemia due to CBS or remethylation defects that require specific treatment and management including perhaps protein-restricted diet and/or vitamin therapy for life. © 2013.

  6. X-ray imaging of differential vascular density in MMP-9-/-, PAR-1-/+, hyperhomocysteinemic (CBS-/+) and diabetic (Ins2-/+) mice.

    Science.gov (United States)

    Givvimani, S; Sen, U; Tyagi, N; Munjal, C; Tyagi, S C

    2011-02-01

    Although protease activated receptor-1 (PAR-1) and matrix metalloproteinase-9 (MMP-9) play significant role in vascular remodelling in hyperhomocysteinemia (HHcy due to cystathionine beta synthase deficiency, CBS-/+) and diabetes, mechanism remains nebulous. We hypothesized that differential vascular density and remodelling in different vascular beds in HHcy and diabetes were responsible for an adaptive metabolic homeostasis during the pathogenesis. To test this hypothesis, vascular density in mice lacking PAR-1, MMP-9, CBS and Insulin-2 gene mutant (Ins2-/+, Akita) was measured and compared with wild type (WT, C57BL/6J) mice. The vascular density was detected by x-ray angiography using KODAK 4000 MM image station, using barium sulphate as contrasting agent. The % vascular density in the hearts of WT, CBS-/+ (HHcy), MMP-9-/-, PAR-1-/+ and Ins2-/+ (type-1 diabetes) was 100 ± 2.8, 85 ± 3.3, 90 ± 3.3, 95 ± 3.8 and 73 ± 1.7, respectively. The vascular density in CBS-/+ and Akita hearts decreased while it was increased in lungs of CBS-/+ and MMP-9-/-.There was decreased vascular density in liver and kidney of Akita mice. Vascular density in brain, kidney and mesentery was decreased in CBS-/+ mice. These findings support the notation that metabolic derangement in diabetes and HHcy causes the chronic decline and/or rarefaction in vascular density.

  7. Identification and Comparative Analysis of CBS Domain-Containing Proteins in Soybean (Glycine max and the Primary Function of GmCBS21 in Enhanced Tolerance to Low Nitrogen Stress

    Directory of Open Access Journals (Sweden)

    Qingnan Hao

    2016-04-01

    Full Text Available Nitrogen is an important macronutrient required for plant growth, and is a limiting factor for crop productivity. Improving the nitrogen use efficiency (NUE is therefore crucial. At present, the NUE mechanism is unclear and information on the genes associated with NUE in soybeans is lacking. cystathionine beta synthase (CBS domain-containing proteins (CDCPs may be implicated in abiotic stress tolerance in plants. We identified and classified a CBS domain–containing protein superfamily in soybean. A candidate gene for NUE, GmCBS21, was identified. GmCBS21 gene characteristics, the temporal expression pattern of the GmCBS21 gene, and the phenotype of GmCBS21 overexpression in transgenic Arabidopsis thaliana under low nitrogen stress were analyzed. The phenotypes suggested that the transgenic Arabidopsis thaliana seedlings performed better under the nitrogen-deficient condition. GmCBS21-overexpressing transgenic plants exhibit higher low nitrogen stress tolerance than WT plants, and this suggests its role in low nitrogen stress tolerance in plants. We conclude that GmCBS21 may serve as an excellent candidate for breeding crops with enhanced NUE and better yield.

  8. Identification and Comparative Analysis of CBS Domain-Containing Proteins in Soybean (Glycine max) and the Primary Function of GmCBS21 in Enhanced Tolerance to Low Nitrogen Stress.

    Science.gov (United States)

    Hao, Qingnan; Shang, Weijuan; Zhang, Chanjuan; Chen, Haifeng; Chen, Limiao; Yuan, Songli; Chen, Shuilian; Zhang, Xiaojuan; Zhou, Xinan

    2016-04-26

    Nitrogen is an important macronutrient required for plant growth, and is a limiting factor for crop productivity. Improving the nitrogen use efficiency (NUE) is therefore crucial. At present, the NUE mechanism is unclear and information on the genes associated with NUE in soybeans is lacking. cystathionine beta synthase (CBS) domain-containing proteins (CDCPs) may be implicated in abiotic stress tolerance in plants. We identified and classified a CBS domain-containing protein superfamily in soybean. A candidate gene for NUE, GmCBS21, was identified. GmCBS21 gene characteristics, the temporal expression pattern of the GmCBS21 gene, and the phenotype of GmCBS21 overexpression in transgenic Arabidopsis thaliana under low nitrogen stress were analyzed. The phenotypes suggested that the transgenic Arabidopsis thaliana seedlings performed better under the nitrogen-deficient condition. GmCBS21-overexpressing transgenic plants exhibit higher low nitrogen stress tolerance than WT plants, and this suggests its role in low nitrogen stress tolerance in plants. We conclude that GmCBS21 may serve as an excellent candidate for breeding crops with enhanced NUE and better yield.

  9. A unique arabinose 5-phosphate isomerase found within a genomic island associated with the uropathogenicity of Escherichia coli CFT073.

    Science.gov (United States)

    Mosberg, Joshua A; Yep, Alejandra; Meredith, Timothy C; Smith, Sara; Wang, Pan-Fen; Holler, Tod P; Mobley, Harry L T; Woodard, Ronald W

    2011-06-01

    Previous studies showed that deletion of genes c3405 to c3410 from PAI-metV, a genomic island from Escherichia coli CFT073, results in a strain that fails to compete with wild-type CFT073 after a transurethral cochallenge in mice and is deficient in the ability to independently colonize the mouse kidney. Our analysis of c3405 to c3410 suggests that these genes constitute an operon with a role in the internalization and utilization of an unknown carbohydrate. This operon is not found in E. coli K-12 but is present in a small number of pathogenic E. coli and Shigella boydii strains. One of the genes, c3406, encodes a protein with significant homology to the sugar isomerase domain of arabinose 5-phosphate isomerases but lacking the tandem cystathionine beta-synthase domains found in the other arabinose 5-phosphate isomerases of E. coli. We prepared recombinant c3406 protein, found it to possess arabinose 5-phosphate isomerase activity, and characterized this activity in detail. We also constructed a c3406 deletion mutant of E. coli CFT073 and demonstrated that this deletion mutant was still able to compete with wild-type CFT073 in a transurethral cochallenge in mice and could colonize the mouse kidney. These results demonstrate that the presence of c3406 is not essential for a pathogenic phenotype.

  10. Genetics Home Reference: hereditary antithrombin deficiency

    Science.gov (United States)

    ... Merck Manual Home Edition for Patients and Caregivers: Thrombophilia National Blood Clot Alliance: Antithrombin Deficiency Orphanet: Hereditary thrombophilia due to congenital antithrombin deficiency Patient Support and ...

  11. [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.

  12. Genetics Home Reference: transcobalamin deficiency

    Science.gov (United States)

    ... deficiency often develop a blood disorder called megaloblastic anemia . Megaloblastic anemia results in a shortage of red blood cells, ... and Prevention: Intellectual Disability (PDF) Children's Hospital Boston: Megaloblastic Pernicious Anemia Children's Hospital Boston: White Blood Cell Disorders CLIMB: ...

  13. Genetics Home Reference: prolidase deficiency

    Science.gov (United States)

    ... Cetta G, Forlino A. Human prolidase and prolidase deficiency: an overview on the characterization of the enzyme involved in proline recycling and on the effects of its mutations. Amino Acids. 2008 Nov;35(4):739-52. doi: 10. ...

  14. Genetics Home Reference: proopiomelanocortin deficiency

    Science.gov (United States)

    ... energy from food taken into the body and energy spent by the body. The correct balance is important to control eating and weight. POMC gene mutations that cause POMC deficiency result in production ...

  15. Helicobacterpy loriinfection and micronutrient deficiencies

    Institute of Scientific and Technical Information of China (English)

    Javed Yakoob; Wasim Jafri; Shahab Abid

    2003-01-01

    It is known that deficiencies of micronutrients due to infections increase morbidity and mortality. This phenomenon depicts itself conspicuously in developing countries.Deficiencies of iron, vitamins A, E, C, B12, etc are widely prevalent among populations living in the third world countries. Helicobacterpylori (Hpylori) infection has a high prevalence throughout the world. Deficiencies of several micronutrients due to Hpylori infection may be concomitantly present and vary from subtle sub-clinical states to severe clinical disorders. These essential trace elementsl micronutrients are involved in host defense mechanisms,maintaining epithelial cell integrity, glycoprotein synthesis,transport mechanisms, myocardial contractility, brain development, cholesterol and glucose metabolism. In this paper Hpyloriinfection in associaed with various micronutrients deficiencies is briefly reviewed.

  16. Vitamin D deficiency in adolescents

    OpenAIRE

    Ashraf T Soliman; Vincenzo De Sanctis; Rania Elalaily; Said Bedair; Islam Kassem

    2014-01-01

    The prevalence of severe vitamin D deficiency (VDD) in adolescents is variable but considerably high in many countries, especially in Middle-east and Southeast Asia. Different factors attribute to this deficiency including lack of sunlight exposure due to cultural dress codes and veiling or due to pigmented skin, and less time spent outdoors, because of hot weather, and lower vitamin D intake. A potent adaptation process significantly modifies the clinical presentation and therefore clinical ...

  17. Iron deficiency and cognitive functions

    OpenAIRE

    Jáuregui-Lobera I

    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...

  18. Iron deficiency and cognitive functions

    OpenAIRE

    Jáuregui-Lobera I

    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...

  19. Lipid, Oxidative and Inflammatory Profile and Alterations in the Enzymes Paraoxonase and Butyrylcholinesterase in Plasma of Patients with Homocystinuria Due CBS Deficiency: The Vitamin B12 and Folic Acid Importance.

    Science.gov (United States)

    Vanzin, Camila Simioni; Mescka, Caroline Paula; Donida, Bruna; Hammerschimidt, Tatiane Grazieli; Ribas, Graziela S; Kolling, Janaína; Scherer, Emilene B; Vilarinho, Laura; Nogueira, Célia; Coitinho, Adriana Simon; Wajner, Moacir; Wyse, Angela T S; Vargas, Carmen Regla

    2015-08-01

    Cystathionine-β-synthase (CBS) deficiency is the main cause of homocystinuria. Homocysteine (Hcy), methionine, and other metabolites of Hcy accumulate in the body of affected patients. Despite the fact that thromboembolism represents the major cause of morbidity in CBS-deficient patients, the mechanisms of cardiovascular alterations found in homocystinuria remain unclear. In this work, we evaluated the lipid and inflammatory profile, oxidative protein damage, and the activities of the enzymes paraoxonase (PON1) and butyrylcholinesterase (BuChE) in plasma of CBS-deficient patients at diagnosis and during the treatment (protein-restricted diet supplemented with pyridoxine, folic acid, betaine, and vitamin B12). We also investigated the effect of folic acid and vitamin B12 on these parameters. We found a significant decrease in HDL cholesterol and apolipoprotein A1 (ApoA-1) levels, as well as in PON1 activity in both untreated and treated CBS-deficient patients when compared to controls. BuChE activity and IL-6 levels were significantly increased in not treated patients. Furthermore, significant positive correlations between PON1 activity and sulphydryl groups and between IL-6 levels and carbonyl content were verified. Moreover, vitamin B12 was positively correlated with PON1 and ApoA-1 levels, while folic acid was inversely correlated with total Hcy concentration, demonstrating the importance of this treatment. Our results also demonstrated that CBS-deficient patients presented important alterations in biochemical parameters, possibly caused by the metabolites of Hcy, as well as by oxidative stress, and that the adequate adherence to the treatment is essential to revert or prevent these alterations.

  20. Expression,purification and identification of I278T-mutant human cystathionine βsynthase%人胱硫醚β合酶I278T突变体的表达、纯化及鉴定

    Institute of Scientific and Technical Information of China (English)

    牛卫宁; 许乐; 羊梦林; 曹珊珊

    2014-01-01

    Objective To investigate the expression and purification I278T-mutant human cystathionineβsynthase(CBS) in E . coli .Methods Site-directed mutagenesis by overlap extension using the polymerase chain reaction (PCR) was employed to construct mutant plasmids pGEX4T-1-CBS(I278T) ,which was induced and expressed in a medium containing 3% ethanol ,purified by affinity chromatography to obtain mutated CBS (I278T) protein .The activity ,UV-visible absorption spectroscopy ,protein particle size and Zeta potential of the purified protein were measured .Results Plasmid pGEX4T-1-CBS(I278T) was successfully constructed .The yield ,the specific activity and activity recovery of purified mutant CBS (I278T ) protein were 2 .3 mg/L ,21 .4 U/mg and 22 .6% .S-adenosylmethionine(AdoMet) with final concentration of 1 mmol/L showed no activation toward mutant CBS (I278T) protein .Ac-cording to UV-visible absorption spectroscopy analysis ,purified mutant CBS(I278T) had characteristic absorption peaks at 429 nm and 550 nm for heme-binding proteins .Protein average particle size was 7 .5 -10 .1 nm ,mainly in the form of tetramers ,and Zeta potential was - 16 .3 mV .Conclusion The methods of expression ,purification and identification of I278T-mutant human cystathionineβsynthase in E .coli were successfully established .%探讨在大肠埃希菌中重组表达和纯化人胱硫醚β合酶CBS(I278T )突变体。方法采用重叠延伸聚合酶链反应(PCR)定点突变技术构建突变质粒pGEX4T-1-CBS(I278T ),在含有3%乙醇的培养基中诱导表达,亲和层析纯化得到突变CBS (I278T)蛋白,测定纯化蛋白的活性、紫外可见吸收光谱、蛋白粒径及Zeta电位。结果成功构建了质粒pGEX4T-1-CBS(I278T)。CBS(I278T )蛋白产率、比活性及酶活性回收率分别为2.3 mg/L、21.4 U/mg、22.6%。终浓度为1 mmol/L的 S-腺苷甲硫氨酸(AdoMet)对突变CBS(I278T)蛋白没有激活作用。紫外可见吸

  1. Clinical manifestation of myeloperoxidase deficiency.

    Science.gov (United States)

    Lanza, F

    1998-09-01

    Myeloperoxidase (MPO), an iron-containing heme protein localized in the azurophilic granules of neutrophil granulocytes and in the lysosomes of monocytes, is involved in the killing of several micro-organisms and foreign cells, including bacteria, fungi, viruses, red cells, and malignant and nonmalignant nucleated cells. Despite the primary role of the oxygen-dependent MPO system in the destruction of certain phagocytosed microbes, subjects with total or partial MPO deficiency generally do not have an increased frequency of infections, probably because other MPO-independent mechanism(s) for microbicidal activity compensate for the lack of MPO. Infectious diseases, especially with species of Candida, have been observed predominantly in MPO-deficient patients who also have diabetes mellitus, but the frequency of such cases is very low, less than 5% of reported MPO-deficient subjects. Evidence from a number of investigators indicates that individuals with total MPO deficiency show a high incidence of malignant tumors. Since MPO-deficient PMNs exhibit in vitro a depressed lytic action against malignant human cells, it can be speculated that the neutrophil MPO system plays a central role in the tumor surveillance of the host. However, any definitive conclusion on the association between MPO deficiency and the occurrence of cancers needs to be confirmed in further clinical studies. Clinical manifestations of this disorder depend on the nature of the defect; an acquired abnormality associated with other hematological or nonhematological diseases has been occasionally described, but the primary deficiency is the form more commonly reported. Another area of interest pertinent to MPO expression is related to the use of anti-MPO monoclonal antibodies for the lineage assignment of acute leukemic cells, the definition of FAB MO acute myeloid leukemia, the identification of biphenotypic acute leukemias, and their distinction from acute leukemia with minimal phenotypic deviation

  2. Interactions among methylenetetrahydrofolate reductase (MTHFR) and cystathionine β-synthase (CBS) polymorphisms - a cross-sectional study: multiple heterozygosis as a risk factor for higher homocysteine levels and vaso-occlusive episodes.

    Science.gov (United States)

    Amaral, F M; Miranda-Vilela, A L; Lordelo, G S; Ribeiro, I F; Daldegan, M B; Grisolia, C K

    2017-02-23

    High plasma homocysteine (Hcy) ​​levels may be responsible for vaso-occlusive episodes and may have acquired and/or genetic causes. This cross-sectional study aimed to investigate the role of methylenetetrahydrofolate reductase (MTHFR; C677T; A1298C) and cystathionine-β-synthase (CBS; T833C/844ins68, G919A) polymorphisms in serum levels of folic acid, vitamin B12 and Hcy, and to verify a possible association between these polymorphisms and the clinical variability. Blood samples of Brazilian patients with a diagnosis of thrombosis were submitted to genotyping by PCR-based methods and serum dosages of folic acid, vitamin B12 and Hcy. Except for the CBS G919A polymorphism, all other genetic markers were in Hardy-Weinberg equilibrium. An increased risk for venous thrombosis was found for the MTHFR 1298CC carriers (OR = 1.688; 95%CI = 0.839-3.398, P = 0.018) and those homozygously mutant for the CBS haplotype 844ins68/T833C (OR = 2.488; 95%CI = 0.501-12.363, P = 0.031), while heterozygous for this CBS haplotype showed an increased risk for higher Hcy levels (OR = 5.900; 95%CI = 1.003-34.691, P = 0.030). Significant interactions were observed among the MTHFR C677T, MTHFR A1298C and CBS haplotype 844ins68/T833C polymorphisms in the results for Hcy levels (P = 0.000), where heterozygous had higher values. Interactions among these polymorphisms can affect serum Hcy levels, where multiple heterozygosis could be a risk factor for vaso-occlusive episodes.

  3. Increased vascular eNOS and cystathionine-γ-lyase protein after 6 weeks oral administration of 3, 5, 7, 3', 4'-pentamethoxyflavone to middle-aged male rats.

    Science.gov (United States)

    Yorsin, Somruedee; Kanokwiroon, Kanyanatt; Radenahmad, Nisaudah; Jansakul, Chaweewan

    2016-11-01

    Effects of treatment of middle-aged male rats with 3, 5, 7, 3', 4'-pentamethoxyflavone (PMF) on vascular and perivascular adipose tissue (PVAT) functions and blood chemistry were investigated. Rats received PMF (22 mg/kg), orally or vehicle, twice a day for 6 weeks. The PMF-treated rats had lower serum glucose, higher HDL-C levels, but no change in other parameters. Thoracic aortic and mesenteric rings of PMF treated rats produced lower maximal contraction to phenylephrine that was normalized by N(G)-nitro-L-arginine (L-NA) or endothelial removal. The aortic- and mesenteric rings of the PMF treated rats showed improved relaxation to acetylcholine, but not to glyceryl trinitrate, and had higher eNOS protein. DL-propargylglycine (PAG) caused greater increase in the baseline tension of the PMF-treated aortic ring and higher contraction to low concentrations of phenylephrine. PVAT lowered the contractile response of the L-NA pretreated aortic rings to phenylephrine for both groups, but PAG had no effect. The cystathionine-γ-lyase (CSE) protein of the thoracic rings, but not of the PVAT, shows increased expression after PMF treatment. Overall, PMF treatment of middle aged rats appeared to increase production of NO and H2S from the blood vessels by upregulating the expression of eNOS and CSE. PMF also decreased fasting serum glucose and increased HDL-C levels, with no toxicity to liver and kidney functions. Thus, PMF is a novel compound for possible use as a health product to prevent and/or to reduce the development of diabetes type II and/or cardiovascular disease.

  4. [Iron deficiency and iron deficiency anemia are global health problems].

    Science.gov (United States)

    Dahlerup, Jens; Lindgren, Stefan; Moum, Björn

    2015-03-10

    Iron deficiency and iron deficiency anemia are global health problems leading to deterioration in patients' quality of life and more serious prognosis in patients with chronic diseases. The cause of iron deficiency and anemia is usually a combination of increased loss and decreased intestinal absorption and delivery from iron stores due to inflammation. Oral iron is first line treatment, but often hampered by intolerance. Intravenous iron is safe, and the preferred treatment in patients with chronic inflammation and bowel diseases. The goal of treatment is normalisation of hemoglobin concentration and recovery of iron stores. It is important to follow up treatment to ensure that these objectives are met and also long-term in patients with chronic iron loss and/or inflammation to avoid recurrence of anemia.

  5. Iron deficiency in blood donors

    Directory of Open Access Journals (Sweden)

    Armando Cortés

    2005-03-01

    Full Text Available Context: Blood donation results in a substantial loss of iron (200 to 250 mg at each bleeding procedure (425 to 475 ml and subsequent mobilization of iron from body stores. Recent reports have shown that body iron reserves generally are small and iron depletion is more frequent in blood donors than in non-donors. Objective: The aim of this study was to evaluate the frequency of iron deficiency in blood donors and to establish the frequency of iron deficiency in blood donors according to sex, whether they were first-time or multi-time donors. Design: From march 20 to April 5, 2004, three hundred potential blood donors from Hemocentro del Café y Tolima Grande were studied. Diagnostic tests: Using a combination of biochemical measurements of iron status: serum ferritin (RIA, ANNAR and the hemoglobin pre and post-donation (HEMOCUE Vital technology medical . Results: The frequency of iron deficiency in potential blood donors was 5%, and blood donors accepted was 5.1%; in blood donors rejected for low hemoglobin the frequency of iron deficiency was 3.7% and accepted blood donors was 1.7% in male and 12.6% in female. The frequency of iron deficiency was higher in multi-time blood donors than in first-time blood donors, but not stadistic significative. Increase nivel accepted hemoglobina in 1 g/dl no incidence in male; in female increase of 0.5 g/dl low in 25% blood donors accepted with iron deficiency, but increased rejected innecesary in 16.6% and increased is 1 g/dl low blood donors female accepted in 58% (7/12, but increased the rejected innecesary in 35.6%. Conclusions: We conclude that blood donation not is a important factor for iron deficiency in blood donors. The high frequency of blood donors with iron deficiency found in this study suggests a need for a more accurate laboratory trial, as hemoglobin or hematocrit measurement alone is not sufficient for detecting and excluding blood donors with iron deficiency without anemia, and ajustes hacia

  6. Iron deficiency and cardiovascular disease.

    Science.gov (United States)

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

    2015-11-01

    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 cardiovascular medicine. Data indicate that iron deficiency has detrimental effects in patients with coronary artery disease, heart failure (HF), and pulmonary hypertension, and possibly in patients undergoing cardiac surgery. Around one-third of all patients with HF, and more than one-half of patients with pulmonary hypertension, are affected by iron deficiency. Patients with HF and iron deficiency have shown symptomatic improvements from intravenous iron administration, and some evidence suggests that these improvements occur irrespective of the presence of anaemia. Improved exercise capacity has been demonstrated after iron administration in patients with pulmonary hypertension. However, to avoid iron overload and T-cell activation, it seems that recipients of cardiac transplantations should not be treated with intravenous iron preparations.

  7. S-Propargyl-cysteine Exerts a Novel Protective Effect on Methionine and Choline Deficient Diet-Induced Fatty Liver via Akt/Nrf2/HO-1 Pathway

    Directory of Open Access Journals (Sweden)

    Wenwen Li

    2016-01-01

    Full Text Available This study investigated the antioxidative effect of S-propargyl-cysteine (SPRC on nonalcoholic fatty liver (NAFLD by treating mice fed a methionine and choline deficient (MCD diet with SPRC for four weeks. We found that SPRC significantly reduced hepatic reactive oxygen species (ROS and methane dicarboxylic aldehyde (MDA levels. Moreover, SPRC also increased the superoxide dismutase (SOD activity. By Western blot, we found that this protective effect of SPRC was importantly attributed to the regulated hepatic antioxidant-related proteins, including protein kinase B (Akt, heme oxygenase-1 (HO-1, nuclear factor erythroid 2-related factor 2 (Nrf2, and cystathionine γ-lyase (CSE, an enzyme that synthesizes hydrogen sulfide. Next, we examined the detailed molecular mechanism of the SPRC protective effect using oleic acid- (OA- induced HepG2 cells. The results showed that SPRC significantly decreased intracellular ROS and MDA levels in OA-induced HepG2 cells by upregulating the phosphorylation of Akt, the expression of HO-1 and CSE, and the translocation of Nrf2. SPRC-induced HO-1 expression and Nrf2 translocation were abolished by the phosphoinositide 3-kinase (PI3K inhibitor LY294002. Moreover, the antioxidative effect of SPRC was abolished by CSE inhibitor DL-propargylglycine (PAG and HO-1 siRNA. Therefore, these results proved that SPRC produced an antioxidative effect on NAFLD through the PI3K/Akt/Nrf2/HO-1 signaling pathway.

  8. Newborn screening for homocystinurias and methylation disorders: systematic review and proposed guidelines.

    Science.gov (United States)

    Huemer, Martina; Kožich, Viktor; Rinaldo, Piero; Baumgartner, Matthias R; Merinero, Begoña; Pasquini, Elisabetta; Ribes, Antonia; Blom, Henk J

    2015-11-01

    Newborn screening (NBS) is justified if early intervention is effective in a disorder generally not detected early in life on a clinical basis, and if sensitive and specific biochemical markers exist. Experience with NBS for homocystinurias and methylation disorders is limited. However, there is robust evidence for the success of early treatment with diet, betaine and/or pyridoxine for CBS deficiency and good evidence for the success of early betaine treatment in severe MTHFR deficiency. These conditions can be screened in dried blood spots by determining methionine (Met), methionine-to-phenylanine (Met/Phe) ratio, and total homocysteine (tHcy) as a second tier marker. Therefore, we recommend NBS for cystathionine beta-synthase and severe MTHFR deficiency. Weaker evidence is available for the disorders of intracellular cobalamin metabolism. Early treatment is clearly of advantage for patients with the late-onset cblC defect. In the early-onset type, survival and non-neurological symptoms improve but the effect on neurocognitive development is uncertain. The cblC defect can be screened by measuring propionylcarnitine, propionylcarnitine-to-acetylcarnitine ratio combined with the second tier markers methylmalonic acid and tHcy. For the cblE and cblG defects, evidence for the benefit of early treatment is weaker; and data on performance of Met, Met/Phe and tHcy even more limited. Individuals homozygous or compound heterozygous for MAT1A mutations may benefit from detection by NBS using Met, which on the other hand also detects asymptomatic heterozygotes. Clinical and laboratory data is insufficient to develop any recommendation on NBS for the cblD, cblF, cblJ defects, glycineN-methyltransferase-, S-adenosylhomocysteinehydrolase- and adenosine kinase deficiency.

  9. [Vitamin A deficiency and xerophtalmia

    Science.gov (United States)

    Diniz, A da S; Santos, L M

    2000-11-01

    OBJECTIVE: To review cases of vitamin A deficiency and the effects of vitamin A supplementation on child morbidity and mortality. METHODS: Articles published in scientific journals, technical and scientific books, and also publications by international organizations were used as source of information. RESULTS: Clinical manifestations of xerophthalmia affect the retina (night blindness), the conjunctiva (conjunctival xerosis, with or without Bitot spots), and the cornea (corneal xerosis). Corneal xerosis may lead to corneal ulceration and liquefactive necrosis (keratomalacia). A priori, these signs and symptoms are the best indicators of vitamin A deficiency; they are, however, extremely rare. Laboratory indicators include Conjunctival Impression Cytology and serum retinol concentrations. The World Health Organization (WHO) recommends the use of two biological markers in order to characterize vitamin A deficiency in a given population. If only one biological marker is used, this marker has to be backed up by a set of at least four additional risk factors. Corneal xerophthalmia should be treated as a medical emergency; In the event of suspected vitamin A deficiency, a 200,000 IU vitamin A dose should be administered orally, repeating the dose after 24 hours (half the dose for infants younger than one year). Vitamin A supplementation in endemic areas may cause a 23 to 30% reduction in the mortality rate of children aged between 6 months and five years, and attenuate the severity of diarrhea. The methods for the control of vitamin A deficiency are available in the short (supplementation with megadoses), medium (food fortification), and long run (diet diversification). CONCLUSION: There is evidence of vitamin A deficiency among Brazilian children. Pediatricians must be aware of the signs and symptoms of this disease, however sporadic they might be. It is of paramount importance that vitamin A be included in public policy plans so that we can ensure the survival of

  10. [Phosphate metabolism and iron deficiency].

    Science.gov (United States)

    Yokoyama, Keitaro

    2016-02-01

    Autosomal dominant hypophosphatemic rickets(ADHR)is caused by gain-of-function mutations in FGF23 that prevent its proteolytic cleavage. Fibroblast growth factor 23(FGF23)is a hormone that inhibits renal phosphate reabsorption and 1,25-dihydroxyvitamin D biosynthesis. Low iron status plays a role in the pathophysiology of ADHR. Iron deficiency is an environmental trigger that stimulates FGF23 expression and hypophosphatemia in ADHR. It was reported that FGF23 elevation in patients with CKD, who are often iron deficient. In patients with nondialysis-dependent CKD, treatment with ferric citrate hydrate resulted in significant reductions in serum phosphate and FGF23.

  11. Iron deficiency in the tropics.

    Science.gov (United States)

    Fleming, A F

    1982-06-01

    Iron in food is classified as belonging to the haem pool, the nonhaem pool, and extraneous sources. Haem iron is derived from vegetable and animal sources with varying bioavailability. Hookworm infestation of the intestinal tract affects 450 million people in the tropics. Schistosoma mansoni caused blood loss in 7 Egyptian patients of 7.5- 25.9 ml/day which is equivalent to a daily loss of iron of .6-7.3 mg daily urinary loss of iron in 9 Egyptian patients. Trichuris trichiura infestation by whipworm is widespread in children with blood loss of 5 ml/day/worm. The etiology of anemia in children besides iron deficiency includes malaria, bacterial or viral infections, folate deficiency and sickle-cell disease. Severe infections cause profound iron-deficiency anemia in children in central American and Malaysia. Plasmodium falciparum malaria-induced anaemia in tropical Africa lowers the mean haemoglobin concentration in the population by 2 g/dI, causing profound anaemia in some. The increased risk of premature delivery, low birthweight, fetal abnormalities, and fetal death is directly related to the degree of maternal anemia. Perinatal mortality was reduced from 38 to 4% in treated anemic mothers. Mental performance was significantly lower in anemic school children and improved after they received iron. Supplements of iron, soy-protein, calcium, and vitamins given to villagers with widespread malnutrition, iron deficiency, and hookworm infestation in Colombia reduced enteric infections in children. Severe iron-deficiency anemia was treated in adults in northern Nigeria by daily in Ferastral 10 ml, which is equivalent to 500 mg of iron per day. Choloroquine, folic acid, rephenium hydroxynaphthoate, and tetrachlorethylene treat adults with severe iron deficiency from hookworm infestation in rural tropical Africa. Blood transfusion is indicated if the patient is dying of anaemia or is pregnant with a haemoglobin concentration 6 gm/dl. In South East Asia, mg per day

  12. Differential diagnosis of iron deficiency

    OpenAIRE

    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...

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

    NARCIS (Netherlands)

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

    2013-01-01

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

  14. Genetics Home Reference: CLPB deficiency

    Science.gov (United States)

    ... Med Genet. 2015 May;52(5):303-11. doi: 10.1136/jmedgenet-2014-102952. Citation on PubMed GeneReview: CLPB Deficiency Kanabus M, Shahni R, Saldanha JW, Murphy E, ... 2015 Mar;38(2):211-9. doi: 10.1007/s10545-015-9813-0. Citation on ...

  15. 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 a

  16. Deficiencies in Indian Joint Operations

    Science.gov (United States)

    2016-05-26

    compartmentalization, and bureaucratic inefficiencies. Indian regional hegemony in South Asia faces significant risks without critically needed reforms to enable...illustrates India’s limited capability to conduct joint operations. Specifically, India demonstrated critical planning deficiencies in joint...society, and this has influenced its understanding of theory and concepts, and its application of those ideas in the development of its own joint

  17. 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.

  18. Deferasirox in pyruvate kinase deficiency

    OpenAIRE

    Deeren, Dries

    2008-01-01

    Deferasirox in pyruvate kinase deficiency phone: +32-51-237437 (Deeren, Dries) (Deeren, Dries) Department of Haematology, Heilig-Hartziekenhuis Roeselare-Menen vzw - Wilgenstraat 2 - B-8800 - Roeselare - BELGIUM (Deeren, Dries) BELGIUM Registration: 2008-09-10 Received: 2008-09-05 Accepted: 2008-09-10 ePublished: 2008-09-23

  19. 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...

  20. Management of Iron Deficiency Anemia

    Science.gov (United States)

    Jimenez, Kristine; Kulnigg-Dabsch, Stefanie

    2015-01-01

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

  1. Congenital β-lipoprotein deficiency

    NARCIS (Netherlands)

    Buchem, F.S.P. van; Pol, G.; Gier, J. de; Böttcher, C.J.F.; Pries, C.

    1966-01-01

    There are several degrees of β-lipoprotein deficiency. If there is no β-lipoprotein present, or if there are only traces of it, the Bassen-Kornzweig syndrome develops. A constant feature of this syndrome is disturbed fat absorption with accumulation of fat in the epithelium of intestinal mucosa and

  2. Homocysteine homeostasis in the rat is maintained by compensatory changes in cystathionine β-synthase, betaine-homocysteine methyltransferase, and phosphatidylethanolamine N-methyltransferase gene transcription occurring in response to maternal protein and folic acid intake during pregnancy and fat intake after weaning.

    Science.gov (United States)

    Chmurzynska, Agata; Malinowska, Anna M

    2011-07-01

    The reactions of the methionine/homocysteine pathway are mediated by several enzymes, including phosphatidylethanolamine N-methyltransferase, cystathionine β-synthase, and betaine-homocysteine methyltransferase. Homocysteine homeostasis is regulated by these enzymes. We hypothesized here that the protein and folic acid content in the maternal diet affects methionine/homocysteine metabolism in the progeny. To test this hypothesis, pregnant rats were fed a diet with normal protein and normal folic acid levels (a modified casein-based AIN-93G diet), a protein-restricted and normal folic acid diet, a protein-restricted and folic acid-supplemented diet, or a normal protein and folic acid-supplemented diet. The progeny were fed either the modified AIN-93G diet or a high-fat lard-based diet. Progeny were analyzed for expression of the phosphatidylethanolamine N-methyltransferase, cystathionine β-synthase, and betaine-homocysteine methyltransferase genes in the liver and for serum homocysteine concentration. Interactions between prenatal and postnatal nutrition were also determined. The progeny of the dams fed the diets supplemented with folic acid showed decreased expression of all 3 genes (P homocysteine concentrations were approximately 15% higher in the male rats (P homocysteine concentrations.

  3. Genetics Home Reference: protein S deficiency

    Science.gov (United States)

    ... my area? Other Names for This Condition hereditary thrombophilia due to protein S deficiency Related Information How are ... Merck Manual Home Edition for Patients and Caregivers: Thrombophilia Orphanet: Hereditary thrombophilia due to congenital protein S deficiency ...

  4. 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 ...

  5. Identifying Causes of Job Performance Deficiencies.

    Science.gov (United States)

    Herem, Maynard A.

    1979-01-01

    A model to guide the search for types of performance deficiencies is set forth within the general framework of systems theory. Five types of problems, singly or in combination, are discussed as causes of deficiencies. (Author)

  6. Iron deficiency--facts and fallacies.

    Science.gov (United States)

    Oski, F A

    1985-04-01

    Iron deficiency occurs in all strata of society, is primarily a result of postnatal feeding practices and not due to congenital deficiencies of iron, can be prevented by appropriate dietary guidance, and, when present, produces important nonhematologic manifestations.

  7. Genetics Home Reference: factor VII deficiency

    Science.gov (United States)

    ... VII deficiency , is caused by mutations in the F7 gene, which provides instructions for making a protein ... about the gene associated with factor VII deficiency F7 Related Information What is a gene? What is ...

  8. Facts about Vitamin K Deficiency Bleeding

    Science.gov (United States)

    ... this? Submit Button Information For… Media Policy Makers Facts about Vitamin K Deficiency Bleeding Recommend on Facebook ... deficiency and VKDB? Protect Your Baby from Bleeds Fact Sheet   Download and print this fact ...

  9. IRON DEFICIENCY IN RURAL GHANAIAN CHILDREN

    African Journals Online (AJOL)

    2001-05-05

    May 5, 2001 ... School of Medical Sciences, University of Science and Technology, ... as controls and newly diagnosed iron-deficient children entering as in-patients. ..... WalterT., Kovacisky J. and Stekel A. Effect of mild iron deficiency.

  10. Genetics Home Reference: primary carnitine deficiency

    Science.gov (United States)

    ... Filippo CA, Pasquali M, Berry SA, Longo N. Expanded newborn screening identifies maternal primary carnitine deficiency. Mol ... deficiency disorders in children. Ann N Y Acad Sci. 2004 Nov;1033:42-51. Review. Citation on ...

  11. Genetics Home Reference: corticosterone methyloxidase deficiency

    Science.gov (United States)

    ... levels of potassium in the blood (hyponatremia and hyperkalemia, respectively). Individuals with corticosterone methyloxidase deficiency can also ... acid in the blood (metabolic acidosis). The hyponatremia, hyperkalemia, and metabolic acidosis associated with corticosterone methyloxidase deficiency ...

  12. Role of the cystathionine β-synthase/H2S system in liver cancer cells and the inhibitory effect of quinolone-indolone conjugate QIC2 on the system.

    Science.gov (United States)

    Jia, Huina; Ye, Juan; You, Jing; Shi, Xiaoyan; Kang, Wenyi; Wang, Tianxiao

    2017-05-01

    Hydrogen sulfide (H2S), the third gasotransmitter, plays important roles in cancer biological processes. As endogenous H2S exerts pro-cancer functions, inhibition of its production in cancer cells may provide a new cancer treatment strategy and be achieved via regulation of the function of cystathionine β-synthase (CBS), one of the main metabolic enzymes synthesizing H2S. This enzyme plays important roles in the development and progression of colon and ovarian cancer, primarily regulating mitochondrial bioenergetics and accelerating cell cycle progression. In the present study, we firstly investigated the role of the CBS/H2S system in human hepatoma cells, and then the inhibitory effect of a quinolone-indolone conjugate QIC2 on this system. When CBS was overexpressed in human hepatoma HepG2 and SMMC-7721 cells, inhibition of endogenous CBS/H2S significantly reduced their viability and growth rate, as well as the proliferation of SMMC-7721 cells. Meanwhile, CBS knockdown caused multiple effects, including apoptosis of SMMC-7721 cells, an increase in the Bcl-2-associated X protein (Bax)/B cell lymphoma/leukemia (Bcl-2) ratio, activation of caspase-3 and polyADP-ribose polymerase (PARP), when compared with the scramble siRNA (Sc siRNA)-transfected groups. Heme oxygenase-1 (HO-1; a microsomal enzyme) expression was significantly decreased while the reactive oxygen species (ROS) level was increased in the CBS siRNA-transfected SMMC-7721 cells. QIC2 significantly reduced SMMC-7721 cell viability in a dose-dependent manner and showed a lower toxicity in human normal liver HL-7702 cells relative to the positive controls sunitinib and doxorubicin (DOX). The compound also inhibited cell proliferation and induced cell apoptosis in SMMC-7721 cells. Further analysis indicated that QIC2 downregulated the CBS/H2S system, decreased both HO-1 protein and glutathione (GSH) levels while increased the ROS level and activated the caspase-3 cascade. Collectively, our results

  13. 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

  14. Cobalamin deficiency in children: A literature review

    OpenAIRE

    Moen, Synne Helland

    2013-01-01

    Objective: The aim of this review is to present cobalamin deficiency in children with a specific focus on infants. Background: Cobalamin deficiency is caused by inadequate intake, malabsorption or inborn errors of vitamin B12 metabolism. Cobalamin deficiency in infants is usually caused by deficiency in the mother. There is often a diagnostic delay among infants because the most frequent symptoms are unspecific, e.g., developmental delay, apathy, hypotonia, anorexia and failure to thrive. Chi...

  15. B6-responsive disorders: a model of vitamin dependency.

    Science.gov (United States)

    Clayton, Peter T

    2006-01-01

    Pyridoxal phosphate is the cofactor for over 100 enzyme-catalysed reactions in the body, including many involved in the synthesis or catabolism of neurotransmitters. Inadequate levels of pyridoxal phosphate in the brain cause neurological dysfunction, particularly epilepsy. There are several different mechanisms that lead to an increased requirement for pyridoxine and/or pyridoxal phosphate. These include: (i) inborn errors affecting the pathways of B(6) vitamer metabolism; (ii) inborn errors that lead to accumulation of small molecules that react with pyridoxal phosphate and inactivate it; (iii) drugs that react with pyridoxal phosphate; (iv) coeliac disease, which is thought to lead to malabsorption of B(6) vitamers; (v) renal dialysis, which leads to increased losses of B(6) vitamers from the circulation; (vi) drugs that affect the metabolism of B(6) vitamers; and (vii) inborn errors affecting specific pyridoxal phosphate-dependent enzymes. The last show a very variable degree of pyridoxine responsiveness, from 90% in X-linked sideroblastic anaemia (delta-aminolevulinate synthase deficiency) through 50% in homocystinuria (cystathionine beta-synthase deficiency) to 5% in ornithinaemia with gyrate atrophy (ornithine delta-aminotransferase deficiency). The possible role of pyridoxal phosphate as a chaperone during folding of nascent enzymes is discussed. High-dose pyridoxine or pyridoxal phosphate may have deleterious side-effects (particularly peripheral neuropathy with pyridoxine) and this must be considered in treatment regimes. None the less, in some patients, particularly infants with intractable epilepsy, treatment with pyridoxine or pyridoxal phosphate can be life-saving, and in other infants with inborn errors of metabolism B(6) treatment can be extremely beneficial.

  16. 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…

  17. Iron-induced nickel deficiency in pecan

    Science.gov (United States)

    Economic loss due to nickel (Ni) deficiency can occur in horticultural and agronomic crops. This study assesses impact of excessive iron (Fe) on expression of Ni deficiency in pecan [Carya illinoinensis (Wangenh.) K. Koch]. Field and greenhouse experiments found Ni deficiency to be inducible by ei...

  18. Vitamin D deficiency in Europe

    DEFF Research Database (Denmark)

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

    2016-01-01

    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...... 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...... deficiency in Europe. DESIGN: The VDSP protocols were applied in 14 population studies [reanalysis of subsets of serum 25(OH)D in 11 studies and complete analysis of all samples from 3 studies that had not previously measured it] by using certified liquid chromatography-tandem mass spectrometry on biobanked...

  19. Iron deficiency anemia in pregnancy.

    Science.gov (United States)

    Di Renzo, Gian Carlo; Spano, Filippo; Giardina, Irene; Brillo, Eleonora; Clerici, Graziano; Roura, Luis Cabero

    2015-11-01

    Anemia is the most frequent derailment of physiology in the world throughout the life of a woman. It is a serious condition in countries that are industrialized and in countries with poor resources. The main purpose of this manuscript is to give the right concern of anemia in pregnancy. The most common causes of anemia are poor nutrition, iron deficiencies, micronutrients deficiencies including folic acid, vitamin A and vitamin B12, diseases like malaria, hookworm infestation and schistosomiasis, HIV infection and genetically inherited hemoglobinopathies such as thalassemia. Depending on the severity and duration of anemia and the stage of gestation, there could be different adverse effects including low birth weight and preterm delivery. Treatment of mild anemia prevents more severe forms of anemia, strictly associated with increased risk of fetal-maternal mortality and morbidity.

  20. DNA repair deficiency in neurodegeneration

    DEFF Research Database (Denmark)

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

    2011-01-01

    : 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......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...

  1. 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.

  2. Molecular Genetics of Lactase Deficiencies

    OpenAIRE

    Kuokkanen, Mikko

    2006-01-01

    Congenital lactase deficiency (CLD) (MIM 223000) is a rare autosomal recessive gastrointestinal disorder characterized by watery diarrhea in infants fed with breast milk or other lactose-containing formulas. The CLD locus was previously assigned by linkage and linkage disequilibrium analyses on 2q21 in 19 Finnish families. In this study, the molecular background of this disorder is reported. The CLD locus was refined in 32 CLD patients in 24 families by using microsatellite and single nucleot...

  3. Carnitine deficiency disorders in children.

    Science.gov (United States)

    Stanley, Charles A

    2004-11-01

    Mitochondrial oxidation of long-chain fatty acids provides an important source of energy for the heart as well as for skeletal muscle during prolonged aerobic work and for hepatic ketogenesis during long-term fasting. The carnitine shuttle is responsible for transferring long-chain fatty acids across the barrier of the inner mitochondrial membrane to gain access to the enzymes of beta-oxidation. The shuttle consists of three enzymes (carnitine palmitoyltransferase 1, carnitine acylcarnitine translocase, carnitine palmitoyl-transferase 2) and a small, soluble molecule, carnitine, to transport fatty acids as their long-chain fatty acylcarnitine esters. Carnitine is provided in the diet (animal protein) and also synthesized at low rates from trimethyl-lysine residues generated during protein catabolism. Carnitine turnover rates (300-500 micromol/day) are deficiency have been described. There is speculation that carnitine supplements might be beneficial in other settings (such as genetic acyl-CoA oxidation defects--"secondary carnitine deficiency", chronic ischemia, hyperalimentation, nutritional carnitine deficiency), but efficacy has not been documented. The formation of abnormal acylcarnitines has been helpful in expanded newborn screening programs using tandem mass-spectrometry of blood spot acylcarnitine profiles to detect genetic fatty acid oxidation defects in neonates. Carnitine-deficient diets (vegetarian) do not have much effect on carnitine pools in adults. A modest 50% reduction in carnitine levels is associated with hyperalimentation in newborn infants, but is of doubtful significance. The above considerations indicate that carnitine does not become rate-limiting unless extremely low; testing the benefits of nutritional supplements may require invasive endurance studies of fasting ketogenesis or muscle and cardiovascular work.

  4. Iron refractory iron deficiency anemia

    OpenAIRE

    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 ad...

  5. Mitochondrial cytochrome c oxidase deficiency.

    Science.gov (United States)

    Rak, Malgorzata; Bénit, Paule; Chrétien, Dominique; Bouchereau, Juliette; Schiff, Manuel; El-Khoury, Riyad; Tzagoloff, Alexander; Rustin, Pierre

    2016-03-01

    As with other mitochondrial respiratory chain components, marked clinical and genetic heterogeneity is observed in patients with a cytochrome c oxidase deficiency. This constitutes a considerable diagnostic challenge and raises a number of puzzling questions. So far, pathological mutations have been reported in more than 30 genes, in both mitochondrial and nuclear DNA, affecting either structural subunits of the enzyme or proteins involved in its biogenesis. In this review, we discuss the possible causes of the discrepancy between the spectacular advances made in the identification of the molecular bases of cytochrome oxidase deficiency and the lack of any efficient treatment in diseases resulting from such deficiencies. This brings back many unsolved questions related to the frequent delay of clinical manifestation, variable course and severity, and tissue-involvement often associated with these diseases. In this context, we stress the importance of studying different models of these diseases, but also discuss the limitations encountered in most available disease models. In the future, with the possible exception of replacement therapy using genes, cells or organs, a better understanding of underlying mechanism(s) of these mitochondrial diseases is presumably required to develop efficient therapy.

  6. [Iodine deficiency in cardiovascular diseases].

    Science.gov (United States)

    Molnár, I; Magyari, M; Stief, L

    1998-08-30

    The thyroid hormone deficiency on cardiovascular function can be characterized with decreased myocardial contractility and increased peripheral vascular resistance as well as with the changes in lipid metabolism. 42 patients with cardiovascular disease (mean age 65 +/- 13 yr, 16 males) were investigated if iodine insufficiency can play a role as a risk factor for the cardiovascular diseases. The patients were divided in 5 subgroups on the ground of the presence of hypertension, congestive heart failure, cardiomyopathy, coronary disfunction and arrhythmia. Urine iodine concentration (5.29 +/- 4.52 micrograms/dl) was detected with Sandell-Kolthoff colorimetric reaction. The most decreased urine iodine concentration was detected in the subgroups with arrhythmia and congestive heart failure (4.7 +/- 4.94 micrograms/dl and 4.9 +/- 4.81 micrograms/dl, respectively). An elevated TSH level was found by 3 patients (5.3 +/- 1.4 mlU/l). An elevation in lipid metabolism (cholesterol, triglyceride) associated with all subgroups without arrhythmia. In conclusion, the occurrence of iodine deficiency in cardiovascular disease is frequent. Iodine supplementation might prevent the worsing effect of iodine deficiency on cardiovascular disease.

  7. Zinc Deficiency in Humans and its Amelioration

    OpenAIRE

    Yashbir Singh Shivay

    2015-01-01

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

  8. Deficiencies in the Management of Iron Deficiency Anemia During Childhood.

    Science.gov (United States)

    Powers, Jacquelyn M; Daniel, Catherine L; McCavit, Timothy L; Buchanan, George R

    2016-04-01

    Limited high-quality evidence supports the management of iron deficiency anemia (IDA). To assess our institutional performance in this area, we retrospectively reviewed IDA treatment practices in 195 consecutive children referred to our center from 2006 to mid-2010. The majority of children were ≤4 years old (64%) and had nutritional IDA (74%). In 11- to 18-year-old patients (31%), the primary etiology was menorrhagia (42%). Many were referred directly to the emergency department and/or prescribed iron doses outside the recommended range. Poor medication adherence and being lost-to-follow-up were common. Substantial improvements are required in the management of IDA.

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

    OpenAIRE

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

    2012-01-01

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

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

    DEFF Research Database (Denmark)

    Frøssing, Signe; Rønø, Birgitte; Hald, Andreas;

    2010-01-01

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

  11. 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.

  12. Alcoholic Myelopathy and Nutritional Deficiency

    Science.gov (United States)

    Koike, Haruki; Nakamura, Tomohiko; Ikeda, Shohei; Takahashi, Mie; Kawagashira, Yuichi; Iijima, Masahiro; Katsuno, Masahisa; Sobue, Gen

    2017-01-01

    A patient with chronic alcoholism presented with myelopathy and low serum folate and cobalamin levels. A 42-year-old alcoholic man had gait disturbance for 4 months. A neurological examination revealed marked spasticity with increased deep tendon reflexes and extensor plantar responses of the lower limbs. His cobalamin level was decreased and his serum folate level was particularly low. His plasma ammonia level was not increased. Abstinence and folic acid and cobalamin supplementation stopped the progression of his neurological deficits. This case indicates that nutritional deficiency should be monitored closely in patients with chronic alcoholism who present with myelopathy. PMID:28049986

  13. 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...

  14. Oxidative Stress Mediates Doxorubicin-Induced Cardiotoxicity by Inhibiting Cystathionine-γ-Lyase%氧化应激通过抑制胱硫醚-γ-裂解酶介导阿霉素的心肌毒性

    Institute of Scientific and Technical Information of China (English)

    郑东诞; 冯鉴强; 王秀玉; 杨春涛; 莫利求; 兰爱平; 胡芬; 郭润民; 沈宁; 陈培熹

    2011-01-01

    目的 探讨氧化应激是否通过抑制胱硫醚-γ-裂解酶的表达及活性介导阿霉素的心肌毒性.方法 应用阿霉素处理大鼠胚胎H9c2心肌细胞以建立阿霉素心肌毒性的细胞模型.在阿霉素处理前60 min用活性氧清除剂N-乙酰半胱氨酸预处理H9c2心肌细胞以观察氧化应激在阿霉素心肌细胞损伤中的作用.应用CCK-8检测心肌细胞存活率;双氯荧光素酶染色及荧光显微镜照相术检测细胞内活性氧水平;Western blot检测胱硫醚-γ-裂解酶的表达;亚甲基蓝显色法检测胱硫醚-γ-裂解酶活性.结果 5 μmol/L阿霉素处理H9c2细胞24h引起明显的心肌毒性,使细胞存活率降低.阿霉素在促进细胞内活性氧生成的同时,还抑制胱硫醚-γ-裂解酶的表达及活性.N-乙酰半胱氨酸不仅抑制阿霉素对活性氧生成的促进作用,还减弱阿霉素的心肌毒性,并能阻断阿霉素对H9c2心肌细胞胱硫醚-γ-裂解酶表达及活性的抑制作用.结论 活性氧可通过抑制心肌细胞胱硫醚-γ-裂解酶的表达及活性介导阿霉素的心肌毒性.%Aim To explore whether oxidative stress mediates doxorubicin-induced cardiotoxicity by inhibiting cystathionine-γ-lyase ( CSE) expression and activity.MethodsH9c2 cells treated with doxorubicin were used as themodel of doxorubicin cardiototoxicity. H9c2 cells were pretreated with N-acetly-L-cysteine (NAC) 60 min prior to treatment with DOX so as to examine the role of oxidative stress in DOX-induced injury. Cell viability was measured by cell counter kit-8. The level of reactive oxygen species ( ROS) was tested by dichlorfluorescein staining and photofluorogra-phy. Expression of CSE was detected by Western blot assay. Activity of CSE was examined by methylene blue test assay. Results Exposure of H9c2 cells to 5 μmol/L doxorubicin induced significant cardiotoxicity, leading to a decrease in cell viability. Doxorubicin not only enhanced ROS generation, but also

  15. Tibetan antelope cystathionine γ -lyase:complete cDNA sequences%高原藏羚羊胱硫醚-γ-裂解酶基因克隆与全序列测定

    Institute of Scientific and Technical Information of China (English)

    李肃; 格日力

    2013-01-01

    Objective To identify the Cystathionine-γ-Lyase(CSE) genes coding sequences molecular cloning , exam the tissues expression spectrums and discuss the hypoxic adaptations mechanisms in Tibetan antelope .Methods The total RNA was extracted ,and the cDNA was captured by reverse transcription RT-PCR ,then identified ,se-quenced and cloned .Results There was 96 .47% homology between the Tibetan antelope gene fragment containing the purpose gene and the cattle gene in gen banks ,thus the result mean the gene which cloned before was CSE gene protein .The length of the CSE gene protein was been detected by designing primers according to the human ,mous , wild boar ,cattle CSEcDNA sequences ,and the CSE gene primers of tibetan antelope which tesied by Pnaman .Conclu-sion CSE gene protein might play an important role in the body of the Tibetan anteplope ,which provide experiment basis to the gene study about adaptation in high altitude hypoxia environment .in the future .%目的:探讨克隆高原藏羚羊胱硫醚-γ-裂解酶(CSE)基因编码区并检测其在成年高原藏羚羊组织中的表达,同时探讨高原藏羚羊低氧适应的分子生物学机制。方法从高原藏羚羊组织中提取总 RNA ,通过逆转录聚合酶链反应(RT-PCR)获得高原藏羚羊 cDNA ,并进行鉴定和测序。结果将含有目的片段克隆后经测序和 Blast分析,结果显示其部分编码序列与 GenBank 中牛 CSE 蛋白基因序列同源性96.47%,表明本实验所克隆的序列为CSE 蛋白基因。根据已知人、褐家鼠、小鼠、野猪、食蟹猴、家牛 CSEcDNA 序列和 Pnaman 软件设计高原藏羚羊 cse基因的引物。结论 CSE mRNA 可能在高原藏羚羊机体较为广泛的区域中发挥着作用,同时为高原低氧适应相关基因的研究提供了实验依据。

  16. 海洛因成瘾大鼠硫化氢/胱硫醚β-合酶体系的变化%Changes of hydrogen sulfide/cystathionine-β-synthase system in hippocampus of heroin-addictive rats

    Institute of Scientific and Technical Information of China (English)

    罗孝美; 陈远寿; 潘贵书; 金寰

    2011-01-01

    目的 观察海洛因成瘾对大鼠硫化氢( hydrogen sulfide,H2S)/胱硫醚β-合酶(cystathionine-β-synthase,CBS)体系产生的影响.方法 实验大鼠分成健康对照组、heroin组、heroin+硫氢化钠(NaHS)组,每组10只.heroin组、heroin+ NaHS组按剂量递增原则皮下注射海洛因9d,对照组按同样方式注射等量生理盐水,heroin+ NaHS组在每次注射海洛因前30 min腹腔注射NaHS,第10天纳洛酮腹腔注射观察戒断症状.采用亚甲基蓝比色法测定大鼠血浆及海马组织H2S含量,Real-time PCR检测海马组织CBS mRNA表达量.结果 heroin组与健康对照组比较,血浆及海马H2S含量均明显降低(P<0.05),CBS mRNA表达量显著增高(P<0.05);heroin+ NaHS组与健康对照组比较,海马H2S含量明显降低(P<0.05);heroin+ NaHS组与heroin组比较,血浆及海马H2S含量明显增高(P<0.05),CBS mRNA表达量明显降低(P<0.05).结论 海洛因依赖可导致大鼠体内H2S水平下降,内源性H2S与CBS之间存在负反馈调节作用,使内源性H2S维持在生理浓度水平.%Objective To determine the effect of heroin addiction on hydrogen sulfide (H2S)/cysta-thionine-β-synthase ( CBS) system in the hippocampus of rats. Methods Experimental rats were randomly divided into 3 groups, control group, heroin group and heroin + NaHS group. The rats of 2 later groups received a subcutaneous injection of heroin at a decreasing dose for 9 d and peritoneal injection of normal saline or NaHS (0.09 mmol/kg) in 30 min before heroin injection. Withdrawal symptoms on the 10th day were used to evaluate the model establishment. The plasma and hippocampal level of H2S were detected by the blue colorimetric method. The expression of CBS mRNA was observed by real time PCR. Results Compared with control group, H2S in plasma and hippocampus was significantly decreased (P <0. 05) while the expression of CBS mRNA was up-regulated (P <0. 05) in heroin group, but hippocampal level of H2S was decreased in

  17. 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.

  18. [Deficiency, disability, neurology and art].

    Science.gov (United States)

    Cano de la Cuerda, Roberto; Collado-Vazquez, Susana

    2010-07-16

    Disability is a complex phenomenon, and the ways it has been conceived, explained and treated have varied notably throughout history. As the years go by, human beings have evolved and, at the same time, so have medicine and art. And therein lies the extraordinary value, from the ontological point of view, of many works of art, which would never have been produced without the intervention of disease and the practice of the medical art. The aim of this work is to address the study of some deficiencies, disabilities and neurological pathologies that have been represented in paintings at different times in history. This article begins with the study of pictures that deal with dwarves and other misnamed freaks of nature that have been represented by painters from Velazquez to Titian or Rubens. The study looks at paintings of cripples, pictures containing the mentally disabled, with examples by Bruegel the Elder or Munch, as well as certain neurological disorders that have been portrayed in paintings, such as Escaping criticism by Pere Borrell or Sad inheritance by Sorolla. Likewise, we also reflect on the trite concept of disease and artistic creativity. The artistic representation of deficiency and disability has evolved in parallel to the feelings of men and women in each period of history and, at the same time, their social evolution. Nowadays, this concept continues to advance and some artists no longer represent the sick person, but instead the illness itself.

  19. Quantitative immunohistochemical analysis of the effect of smoking on the cystathionine-γ-lyase in the rat thoracic aorta%免疫组化定量分析吸烟对大鼠胸主动脉中胱硫醚-γ-裂解酶的影响

    Institute of Scientific and Technical Information of China (English)

    张涛; 刘朝中; 张海涛; 谈诚; 黄丛春; 孟如松; 任志霞

    2011-01-01

    Objective To quantitatively study the effect of tobacco smoking on cystathionine--γ-lyase in the rat thoracic aorta. Methods 16 10-week-old male SD rats were randomly divided into the control group (fed under normal breathing conditions) and smoking group (smoking 20 cigarettes per day,for 90 days, n = 8 ). The rats were killed by cervical dislocation, and the thoracic aorta was taken and fixed in 10% formalin for 1 to 2 days. The sections were immunohistochemically stained for cystathionine-γ-lyase.The cystathionine-γ-lyase area density and optical density in the microscopic images of the rat thoracic a-orta were quantitatively analyzed. Results The area density of cystathionine-γ-lyase expression in the thoracic aorta of the smoking group was 6.79 ± 1.04, significantly lower than that of 14.98 ± 2. 32 in the control group (P<0.01). The optical density in the smoking group was 0. 15 ±0.04, also significantly lower than that of 0.21 ±0.03 in the control group (P <0. 01). Conclusion Smoking can decrease the concentration of cyatathionine-γ-lyase in the rat thoracic aorta.%目的 定量研究烟草烟雾对大鼠胸主动脉的胱硫醚-γ-裂解酶影响.方法 16只10周龄SD大鼠随机分为对照组(正常呼吸条件下饲养)和吸烟组(每天吸烟20支,连续90 d),每组8只.被动吸烟大鼠模型造完后断颈处死,取其近心端胸主动脉于10%的福尔马林固定1~2 d,采用免疫组化染色和显微图像定量分析法,观察大鼠胸主动脉胱硫醚-γ-裂解酶的面积密度和光密度.结果 吸烟组的大鼠胸主动脉中胱硫醚-γ-裂解酶的表达面积密度明显低于对照组(6.79±1.04vs.14.98±2.32,P<0.01);其光密度值也明显低于对照组(0.15±0.04 vs.0.21±0.03,P<0.01).结论 吸烟可导致大鼠胸主动脉中的胱硫醚-γ-裂解酶含量降低.

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

    Science.gov (United States)

    Camaschella, Clara

    2017-02-13

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

  1. Cryptosporidiosis in the acquired immune deficiency syndrome.

    Science.gov (United States)

    Cooper, D A; Wodak, A; Marriot, D J; Harkness, J L; Ralston, M; Hill, A; Penny, R

    1984-10-01

    Cryptosporidiosis was found in a patient with the acquired immune deficiency syndrome. The microbiological and morphological features of this newly recognized opportunistic infection are distinctive and diagnostic.

  2. 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...

  3. Mannose Binding Lectin Deficiency and Clinical Features

    Directory of Open Access Journals (Sweden)

    Ertugrul Erken

    2013-08-01

    Full Text Available Innate immunity consists of macrophages, neutrophils, natural killer cells, mucosal immunuglobulins and the comlement system. Mannose binding lectin (MBL takes part in innate immunity through opsonisation and complement activation. MBL deficiency is associated with some infections and autoimmune disorders. However some studies indicate that MBL deficiency alone is not essential for immunity but it may intensify the clinic picture of an immune deficiency that already exists. This article refers to clincal studies related to MBL and brings up the clinical importance of MBL deficiency. [Archives Medical Review Journal 2013; 22(4.000: 565-574

  4. Generalised hyperpigmentation in vitamin B12 deficiency.

    Science.gov (United States)

    Santra, Gouranga; Paul, Rudrajit; Ghosh, Sumit Kr; Chakraborty, Debojyoti; Das, Shubhabrata; Pradhan, Sourav; Das, Abhishek

    2014-08-01

    In developing countries like India, nutritional deficiencies are prevalent and hyperpigmentation due to protein energy malnutrition, zinc deficiency and pellagra are common. Indian women, especially vegetarian are prone to vitamin B12 deficiency. Vitamin B12 deficiency can present as anaemia, neurological defect, gastrointestinal symptoms or dementia. Hyperpigmentation as the first presentation of Vitamin B12 deficiency is rare. Our patient, a 45 year-old Hindu vegetarian female presented to us with generalized hyperpigmentation. Examination revealed associated anaemia and peripheral neuropathy. Laboratory investigation confirmed vitamin B12 deficiency. Clinical features along with hyperpigmentation improved with vitamin B12 supplementation. We report this case to highlight this rare manifestation of vitamin B12 deficiency. A high index of clinical suspicion is warranted to diagnose the case. Since India is a country with a large number of potential vitamin B12 deficiency cases, the physicians need to be aware of all the varied manifestations of this vitamin deficiency. In case of hyperpigmentation, nutritional aspect must be ruled out as it is reversible. Early replacement therapy may also help to prevent morbidities like dementia and neuropathy.

  5. Genetics Home Reference: factor X deficiency

    Science.gov (United States)

    ... deficiency occurs in approximately 1 per million individuals worldwide. Related Information What information about a genetic condition can statistics provide? Why are some genetic conditions more common ...

  6. Iron deficiency anemia in heart failure.

    Science.gov (United States)

    Arora, Natasha P; Ghali, Jalal K

    2013-07-01

    Anemia and iron deficiency are quite prevalent in patients with heart failure (HF) and may overlap. Both anemia and iron deficiency are associated with worse symptoms and adverse clinical outcomes. In the past few years, there has been an enormous interest in the subject of iron deficiency and its management in patients with HF. In this review, the etiology and relevance of iron deficiency, iron metabolism in the setting of HF, studies on iron supplementation in patients with HF and potential cardiovascular effects of subclinical iron overload are discussed.

  7. The impact of maternal iron deficiency and iron deficiency anemia on child’s health

    OpenAIRE

    Abu-Ouf, Noran M.; Mohammed M. Jan

    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...

  8. 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...

  9. Photodissociation of neutron deficient nuclei

    Energy Technology Data Exchange (ETDEWEB)

    Sonnabend, K.; Babilon, M.; Hasper, J.; Mueller, S.; Zarza, M.; Zilges, A. [TU Darmstadt, Institut fuer Kernphysik, Darmstadt (Germany)

    2006-03-15

    The knowledge of the cross sections for photodissociation reactions like e.g. ({gamma}, n) of neutron deficient nuclei is of crucial interest for network calculations predicting the abundances of the so-called p nuclei. However, only single cross sections have been measured up to now, i.e., one has to rely nearly fully on theoretical predictions. While the cross sections of stable isotopes are accessible by experiments using real photons, the bulk of the involved reactions starts from unstable nuclei. Coulomb dissociation (CD) experiments in inverse kinematics might be a key to expand the experimental database for p-process network calculations. The approach to test the accuracy of the CD method is explained. (orig.)

  10. [Iron deficiency in the elderly].

    Science.gov (United States)

    Helsen, Tuur; Joosten, Etienne

    2016-06-01

    Anemia is a common diagnosis in the geriatric population, especially in institutionalized and hospitalized elderly. Most common etiologies for anemia in elderly people admitted to a geriatric ward are iron-deficiency anemia and anemia associated with chronic disease. Determination of serum ferritin is the most used assay in the differential diagnosis, despite low sensitivity and moderate specificity. New insights into iron homeostasis lead to new diagnostic assays such as serum hepcidin, serum transferrin receptor and reticulocyte hemoglobin equivalent.Importance of proper diagnosis and treatment for this population is large since there is a correlation between anemia and morbidity - mortality. Anemia is usually defined as hemoglobin less than 12 g/dl for women and less than 13 g/dl for men. There is no consensus for which hemoglobinvalue an investigation into underlying pathology is obligatory. This needs to be evaluated depending on functional condition of the patient.

  11. [delta-Aminolevulinate dehydratase deficiency].

    Science.gov (United States)

    Fujita, H; Ishida, N; Akagi, R

    1995-06-01

    delta-Aminolevulinate dehydratase (ALAD: E. C. 4.2.1.24), the second enzyme in the heme biosynthetic pathway, condenses two moles of delta-aminolevulinic acid to form porphobilinogen. ALAD deficiency is well known to develop signs and symptoms of typical hepatic porphyria, and classified into three categories as follows: (i) ALAD porphyria, a genetic defect of the enzyme, (ii) tyrosinemia type I, a genetic defect of fumarylacetoacetase in the tyrosine catabolic pathway, producing succinylacetone (a potent inhibitor of ALAD), and (iii) ALAD inhibition by environmental hazards, such as lead, trichloroethylene, and styrene. In the present article, we will describe molecular and biochemical mechanisms to cause the enzyme defect to discuss the significance of ALAD defect on human health.

  12. Carbohydrate deficient transferrin and alcoholism.

    Science.gov (United States)

    Solomons, Hilary Denis

    2012-06-01

    Alcohol abuse is an important public health problem, with major implications in patients with a pre-existing liver pathology of viral origin. Hepatitis C, for example, is one of the diseases in which alcohol consumption can lead to the transition from a fairly benign outline to a potentially life-threatening liver disease. Alcohol abuse is usually identified on the basis of clinical judgment, alcoholism related questionnaires, laboratory tests and, more recently, biomarkers. Also on this list of tests, carbohydrate deficient transferrin (CDT) is widely available and useful for determining recent alcohol consumption, particularly when corroborated with elevation of other liver-associated enzymes. Clinicians should be aware of the indications and limitations of this test in order to better evaluate alcohol consumption in their patients.

  13. Genetic causes for iron deficiency

    OpenAIRE

    Saad,Sara Teresinha O.

    2010-01-01

    As causas genéticas de deficiência de ferro, real ou funcional, ocorrem por defeitos em muitas proteínas envolvidas na absorção e metabolismo de ferro. Neste capítulo descreveremos sucintamente causas genéticas de carência de ferro para a síntese de hemoglobina, que cursa então com anemia microcítica e hipocrômica. Ressalto que estas são alterações raras, com poucas descrições na literatura. Em alguns casos, o ferro funcional não está disponível para os eritroblastos sintetizarem hemoglobina,...

  14. B12 Deficiency with Children

    Directory of Open Access Journals (Sweden)

    Selahattin Katar

    2007-01-01

    Full Text Available Aim of the study: to rewieved the clinical and laboratory properties of seven cases with megaloblastic anemia. Clinical and laboratory findings of seven cases with megaloblastic anemia are described. İt is determined that all of the patients received little or no animal products by nutritional history. Clinically apatite, malasia, headeche, otism, and parestheia in the lower extremities and foods were present in patients. On physical examination; four patients had glossit, four had hyporeflexia, one had ataxia. Folat level was normal and B12 vitamin level was low in all patients. The MCV (mean corpuscular volume was normal in three patients. Hypersegmentation of neutrophil was observed in all patients, leukopenia in two, and trombocytopenia was observed in one patient.Conclusion: it is suggested B12 vitamin deficiency in the patients that received little or no animal products by nutritional history. However, hypersegmentation of neutrophil in peripheral blood sample is an important finding for diagnosis of megaloblastic anemia.

  15. Vitamin A deficiency in quail

    Science.gov (United States)

    Nestler, R.B.; Bailey, W.W.

    1943-01-01

    Two experiments were conducted to determine the symptoms of avitaminosis A in growing and adolescent bobwhites. Chicks from parents that have received a diet rich in vitamin A may have enough stored to carry them a week or ten days on a growing diet deficient in vitamin A before symptoms of deficiency occur. The first sign is ruffled feathering, with the wing primaries standing out from the body and drooping. Ophthalmia in one or both eyes occurs and may close the eyes completely, but this condition is not severe in all cases and may not even be noticeable. Birds show poor growth, loss of appetite, and weakness before death. Under the conditions of the experiments discussed herein, death may occur in the fourth or fifth week, and mortality is high......Postmortem examination may reveal visceral gout with thick deposits of urates on the kidneys, in the ureters, on the heart, in the proventriculus, and occasionally covering all the viscera. There may also be hemorrhage of the heart and other organs....Adolescent quail reared on a diet rich in vitamin A may be able to live through the winter on a maintenance diet low in this vitamin without showing symptoms of avitaminosis, but some individuals whose storage of vitamin A in the liver is not as great as that of others may succumb to visceral gout.....A growing mash for quail which contains sufficient vitamin A when fresh may, after a period of storage, lose enough of the vitamin to cause the characteristic symptoms of avitaminosis A to appear.

  16. Vitamin D deficiency in adolescents.

    Science.gov (United States)

    Soliman, Ashraf T; De Sanctis, Vincenzo; Elalaily, Rania; Bedair, Said; Kassem, Islam

    2014-11-01

    The prevalence of severe vitamin D deficiency (VDD) in adolescents is variable but considerably high in many countries, especially in Middle-east and Southeast Asia. Different factors attribute to this deficiency including lack of sunlight exposure due to cultural dress codes and veiling or due to pigmented skin, and less time spent outdoors, because of hot weather, and lower vitamin D intake. A potent adaptation process significantly modifies the clinical presentation and therefore clinical presentations may be subtle and go unnoticed, thus making true prevalence studies difficult. Adolescents with severe VDD may present with vague manifestations including pain in weight-bearing joints, back, thighs and/or calves, difficulty in walking and/or climbing stairs, or running and muscle cramps. Adaptation includes increased parathormone (PTH) and deceased insulin-like growth factor-I (IGF-I) secretion. PTH enhances the tubular reabsorption of Ca and stimulates the kidneys to produce 1, 25-(OH) 2D3 that increases intestinal calcium absorption and dissolves the mineralized collagen matrix in bone, causing osteopenia and osteoporosis to provide enough Ca to prevent hypocalcaemia. Decreased insulin like growth factor-I (IGF-I) delays bone growth to economize calcium consumption. Radiological changes are not uncommon and include osteoporosis/osteopenia affecting long bones as well as vertebrae and ribs, bone cysts, decalcification of the metaphysis of the long bones and pseudo fractures. In severe cases pathological fractures and deformities may occur. Vitamin D treatment of adolescents with VDD differs considerably in different studies and proved to be effective in treating all clinical, biochemical, and radiological manifestations. Different treatment regiments for VDD have been discussed and presented in this mini-review for practical use. Adequate vitamin D replacement after treating VDD, improving calcium intake (milk and dairy products), encouraging adequate exposure

  17. How common is vitamin B12 deficiency?

    Science.gov (United States)

    In considering the vitamin B-12 fortification of flour, it is important to know who is at risk of vitamin B-12 deficiency and whether those individuals would benefit from flour fortification.This article reviews current knowledge of the prevalence and causes of vitamin B-12 deficiency and considers ...

  18. Growth Hormone Deficiency, Brain Development, and Intelligence

    Science.gov (United States)

    Meyer-Bahlburg, Heino F. L.; And Others

    1978-01-01

    Available from: American Medical Association, 535 N. Dearborn Street, Chicago, Illinois 60610. In order to determine what effect, if any, growth hormone (GH) has on human brain development, 29 patients (mean age 11.7 years) with GH deficiency were selected according to the following criteria: no evidence of reversible GH deficiency, onset of…

  19. Duodenal Amyloidosis Masquerading as Iron Deficiency Anemia

    Science.gov (United States)

    Hurairah, Abu

    2016-01-01

    The present study is a unique illustration of duodenal amyloidosis initially manifesting with iron deficiency anemia. It underscores the importance of clinical suspicion of amyloidosis while performing upper gastrointestinal endoscopy with a biopsy to establish the definite diagnosis in patients with unexplained iron deficiency anemia. PMID:27625911

  20. Dietary recommendations in patients with deficiency anaemia

    Directory of Open Access Journals (Sweden)

    A. Santoyo-Sánchez

    2015-07-01

    Nutritionists should understand deficiency anaemia, and physicians, particularly general practitioners, should be aware of dietary requirements. In this article, therefore, both health care professionals have come together to briefly explain, with examples, the type of diet that should be recommended to patients with deficiency anaemia.

  1. An update on serine deficiency disorders

    NARCIS (Netherlands)

    van der Crabben, S. N.; Verhoeven-Duif, N. M.; Brilstra, E. H.; Van Maldergem, L.; Coskun, T.; Rubio-Gozalbo, E.; Berger, R.; de Koning, T. J.

    Serine deficiency disorders are caused by a defect in one of the three synthesising enzymes of the L-serine biosynthesis pathway. Serine deficiency disorders give rise to a neurological phenotype with psychomotor retardation, microcephaly and seizures in newborns and children or progressive

  2. Psychomotor development in children with iron deficiency and iron-deficiency anemia.

    Science.gov (United States)

    Pala, Emin; Erguven, Muferet; Guven, Sirin; Erdogan, Makbule; Balta, Tulin

    2010-09-01

    Iron deficiency and iron-deficiency anemia are the most common nutritional deficiencies in children, especially in developing countries. Iron-deficiency anemia in infancy is associated with impaired neurodevelopment. Studies have shown an association between iron deficiency without anemia and adverse effects on psychomotor development. To determine the effects of iron deficiency and iron-deficiency anemia on psychomotor development in childhood. . We evaluated psychomotor development in healthy children with iron deficiency and iron-deficiency anemia with the use of the Denver II Developmental Screening Test (DDST-II). If the child score was more than 90th percentile compared to children in the same age group, the test was scored as "delay" it was scored as a "caution" if the child score was between the 75th and 90th percentiles. The test result was interpreted as "normal," if there was no delay and only one "caution" for any item. If the child had one or more "delays" or more than two "cautions," the result was classified as "abnormal." DDST-II scores were abnormal in 67.3% of subjects with iron-deficiency anemia, 21.6% of those with iron deficiency, and 15.0% of control subjects. The difference from the control group in the percentage of abnormal scores was significant for subjects with iron-deficiency anemia (p iron deficiency (p = 0.203); p > .05. (p-value, post-hoc comparison of 2 groups.) Iron-deficiency anemia impaired psychomotor development during childhood. However, the evidence on the adverse effects of iron deficiency remains controversial. The Denver II Developmental Screening Test is a valuable test to detect early developmental delays, especially in infants with risk factors.

  3. Prevalence of Color Vision Deficiency in Qazvin

    Directory of Open Access Journals (Sweden)

    Mohammad khalaj

    2014-01-01

    Full Text Available Background: Color vision deficiency (CVD is an X chromosome-linked recessive autosomal dominant. Determine the prevalence of color blindness in Qazvin population. Materials and Methods: In a cross sectional study color vision deficiency examined in 1853 individuals with age 10-25 years old who participated in private clinics and eye clinic of Bu-Ali hospital in Qazvin in 2010. The screening of color vision deficiency was performed using Ishihara test. Data were analyzed by SPSS-16 with χP2P test with p<0.05. Results: Mean age of participant was 17.86±4.48 years. 59.5% of them were female. 3.49% of the total population had color vision deficiency that 0.93% and 2.56% were female and male respectively. Conclusion: color vision deficiency must be noticed by decision makers in health field for screen planning.

  4. Molecular diagnosis of coenzyme Q10 deficiency.

    Science.gov (United States)

    Yubero, Delia; Montero, Raquel; Armstrong, Judith; Espinós, Carmen; Palau, Francesc; Santos-Ocaña, Carlos; Salviati, Leonardo; Navas, Placido; Artuch, Rafael

    2015-01-01

    Coenzyme Q10 (CoQ) deficiency syndromes comprise a growing number of neurological and extraneurological disorders. Primary-genetic but also secondary CoQ deficiencies have been reported. The biochemical determination of CoQ is a good tool for the rapid identification of CoQ deficiencies but does not allow the selection of candidate genes for molecular diagnosis. Moreover, the metabolic pathway for CoQ synthesis is an intricate and not well-understood process, where a large number of genes are implicated. Thus, only next-generation sequencing techniques (either genetic panels of whole-exome and -genome sequencing) are at present appropriate for a rapid and realistic molecular diagnosis of these syndromes. The potential treatability of CoQ deficiency strongly supports the necessity of a rapid molecular characterization of patients, since primary CoQ deficiencies may respond well to CoQ treatment.

  5. [Vitamin B12 deficiency in the elderly].

    Science.gov (United States)

    Leischker, A H; Kolb, G F

    2015-01-01

    The prevalence of vitamin B12 deficiency increases with age. Patients with dementia and spouses of patients with dementia are at special risk for the development of vitamin B12 deficiency. In a normal diet this vitamin is present only in animal source foods; therefore, vegans frequently develop vitamin B12 deficiency if not using supplements or foods fortified with cobalamin. Apart from dementia, most of these manifestations are completely reversible under correct therapy; therefore it is crucial to identify and to treat even atypical presentations of vitamin B12 deficiency as early as possible. This article deals with the physiology and pathophysiology of vitamin B12 metabolism. A practice-oriented algorithm which also considers health economic aspects for a rational laboratory diagnosis of vitamin B12 deficiency is presented. In cases with severe neurological symptoms, therapy should be parenteral, especially initially. For parenteral treatment, hydroxocobalamin is the drug of choice.

  6. [Trial of indirect screening of tetrahydrobiopterin deficiency].

    Science.gov (United States)

    Ferraris, S; Guardamagna, O; Bracco, G; Ponzone, A

    1987-01-01

    The possibility of an early diagnosis of tetrahydrobiopterin deficiency among hyperphenylalaninemic infants, when specific screening tests cannot be performed, was evaluated. Three tetrahydrobiopterin deficient patients, two with dihydropteridine reductase deficiency and one with dihydrobiopterin synthetase deficiency were examined together with their parents and compared with twelve phenylketonuric patients, their parents and sixteen normal subjects. The parameters considered in the hyperphenylalaninemic patients (degree of neonatal hyperphenylalaninemia, phenylalanine lowering speed in response to a restricted diet, dietary tolerance to phenylalanine, oral phenylalanine load) were found to be insufficiently or lately indicative. By contrast, heterozygosity tests (molar ratio (Phe)2/Tyr and sigma discriminant function) performed on the parents allowed a suspicion of tetrahydrobiopterin deficiency, the definite diagnosis being of course based upon specific investigations.

  7. Vitamin D deficiency in adolescents

    Directory of Open Access Journals (Sweden)

    Ashraf T Soliman

    2014-01-01

    Full Text Available The prevalence of severe vitamin D deficiency (VDD in adolescents is variable but considerably high in many countries, especially in Middle-east and Southeast Asia. Different factors attribute to this deficiency including lack of sunlight exposure due to cultural dress codes and veiling or due to pigmented skin, and less time spent outdoors, because of hot weather, and lower vitamin D intake. A potent adaptation process significantly modifies the clinical presentation and therefore clinical presentations may be subtle and go unnoticed, thus making true prevalence studies difficult. Adolescents with severe VDD may present with vague manifestations including pain in weight-bearing joints, back, thighs and/or calves, difficulty in walking and/or climbing stairs, or running and muscle cramps. Adaptation includes increased parathormone (PTH and deceased insulin-like growth factor-I (IGF-I secretion. PTH enhances the tubular reabsorption of Ca and stimulates the kidneys to produce 1, 25-(OH 2D3 that increases intestinal calcium absorption and dissolves the mineralized collagen matrix in bone, causing osteopenia and osteoporosis to provide enough Ca to prevent hypocalcaemia. Decreased insulin like growth factor-I (IGF-I delays bone growth to economize calcium consumption. Radiological changes are not uncommon and include osteoporosis/osteopenia affecting long bones as well as vertebrae and ribs, bone cysts, decalcification of the metaphysis of the long bones and pseudo fractures. In severe cases pathological fractures and deformities may occur. Vitamin D treatment of adolescents with VDD differs considerably in different studies and proved to be effective in treating all clinical, biochemical, and radiological manifestations. Different treatment regiments for VDD have been discussed and presented in this mini-review for practical use. Adequate vitamin D replacement after treating VDD, improving calcium intake (milk and dairy products, encouraging

  8. Infections Revealing Complement Deficiency in Adults

    Science.gov (United States)

    Audemard-Verger, A.; Descloux, E.; Ponard, D.; Deroux, A.; Fantin, B.; Fieschi, C.; John, M.; Bouldouyre, A.; Karkowsi, L.; Moulis, G.; Auvinet, H.; Valla, F.; Lechiche, C.; Davido, B.; Martinot, M.; Biron, C.; Lucht, F.; Asseray, N.; Froissart, A.; Buzelé, R.; Perlat, A.; Boutboul, D.; Fremeaux-Bacchi, V.; Isnard, S.; Bienvenu, B.

    2016-01-01

    Abstract Complement system is a part of innate immunity, its main function is to protect human from bacterial infection. As genetic disorders, complement deficiencies are often diagnosed in pediatric population. However, complement deficiencies can also be revealed in adults but have been poorly investigated. Herein, we describe a case series of infections revealing complement deficiency in adults to study clinical spectrum and management of complement deficiencies. A nationwide retrospective study was conducted in French university and general hospitals in departments of internal medicine, infectious diseases enrolling patients older than 15 years old who had presented at least one infection leading to a complement deficiency diagnosis. Forty-one patients included between 2002 and 2015 in 19 different departments were enrolled in this study. The male-to-female ratio was 1.3 and the mean age at diagnosis was 28 ± 14 (15–67) years. The main clinical feature was Neisseria meningitidis meningitis 75% (n = 31/41) often involving rare serotype: Y (n = 9) and W 135 (n = 7). The main complement deficiency observed was the common final pathway deficiency 83% (n = 34/41). Half of the cohort displayed severe sepsis or septic shock at diagnosis (n = 22/41) but no patient died. No patient had family history of complement deficiency. The mean follow-up was 1.15 ± 1.95 (0.1–10) years. Half of the patients had already suffered from at least one infection before diagnosis of complement deficiency: meningitis (n = 13), pneumonia (n = 4), fulminans purpura (n = 1), or recurrent otitis (n = 1). Near one-third (n = 10/39) had received prophylactic antibiotics (cotrimoxazole or penicillin) after diagnosis of complement deficiency. The vaccination coverage rate, at the end of the follow-up, for N meningitidis, Streptococcus pneumonia, and Haemophilius influenzae were, respectively, 90% (n = 33/37), 47% (n = 17/36), and 35

  9. Genetics Home Reference: ataxia with vitamin E deficiency

    Science.gov (United States)

    ... Home Health Conditions ataxia with vitamin E deficiency ataxia with vitamin E deficiency Printable PDF Open All ... Javascript to view the expand/collapse boxes. Description Ataxia with vitamin E deficiency is a disorder that ...

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

    Science.gov (United States)

    ... refractory iron deficiency anemia iron-refractory iron deficiency anemia Enable Javascript to view the expand/collapse boxes. ... All Close All Description Iron-refractory iron deficiency anemia is one of many types of anemia , which ...

  11. Genetics Home Reference: alpha-methylacyl-CoA racemase deficiency

    Science.gov (United States)

    ... Email Facebook Twitter Home Health Conditions AMACR deficiency alpha-methylacyl-CoA racemase deficiency Enable Javascript to view ... boxes. Download PDF Open All Close All Description Alpha-methylacyl-CoA racemase (AMACR) deficiency is a disorder ...

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

    DEFF Research Database (Denmark)

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

    2009-01-01

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

  13. Seventeen Alpha-hydroxylase Deficiency

    Directory of Open Access Journals (Sweden)

    Siew-Lee Wong

    2006-01-01

    Full Text Available Seventeen a-hydroxylase deficiency (17OHD is a rare form of congenital adrenal hyperplasia in which defects in the biosynthesis of cortisol and sex steroid result in mineralocorticoid excess, hypokalemic hypertension and sexual abnormalities such as pseudohermaphroditism in males, and sexual infantilism in females. The disease is inherited in an autosomal recessive pattern, and is caused by mutations in the gene encoding cytochrome P450c17 (CYP17, which is the single polypeptide that mediates both 17α-hydroxylase and 17,20-lyase activities. We report the case of a 15-year-old patient with 17OHD who had a female phenotype but male karyotype (46,XY. The diagnosis was made based on classical clinical features, biochemical data and molecular genetic study. Two mutations were identified by polymerase chain reaction amplification and sequencing, including a S106P point mutation in exon 2 and a 9-bp (GACTCTTTC deletion from nucleotide position 1519 in exon 8 of CYP17. The first of these mutations was found in the father and the second in the mother, and both have been previously reported in Asia. The patient's hypertension and hypokalemia resolved after glucocorticoid replacement and treatment with potassium-sparing diuretics. Sex hormone replacement was prescribed for induction of sexual development and reduction of the final height. Prophylactic gonadectomy was scheduled. In summary, 17OHD should be suspected in patients with hypokalemic hypertension and lack of secondary sexual development so that appropriate therapy can be implemented.

  14. Deficient Approaches to Human Neuroimaging

    Directory of Open Access Journals (Sweden)

    Johannes eStelzer

    2014-07-01

    Full Text Available Functional magnetic resonance imaging (fMRI is the workhorse of imaging-based human cognitive neuroscience. The use of fMRI is ever-increasing; within the last 4 years more fMRI studies have been published than in the previous 17 years. This large body of research has mainly focused on the functional localization of condition- or stimulus-dependent changes in the blood-oxygenation-level dependent (BOLD signal.In recent years, however, many aspects of the commonly practiced analysis frameworks and methodologies have been critically reassessed. Here we summarize these critiques, providing an overview of the major conceptual and practical deficiencies in widely used brain-mapping approaches, and exemplify some of these issues by the use of imaging data and simulations. In particular, we discuss the inherent pitfalls and shortcomings of methodologies for statistical parametric mapping. Our critique emphasizes recent reports of excessively high numbers of both false positive and false negative findings in fMRI brain mapping. We outline our view regarding the broader scientific implications of these methodological considerations and briefly discuss possible solutions.

  15. Testosterone deficiency and cardiovascular mortality

    Institute of Scientific and Technical Information of China (English)

    Abraham Morgentaler

    2015-01-01

    New concerns have been raised regarding cardiovascular (CV) risks with testosterone (T) therapy (TTh). These concerns are based primarily on two widely reported retrospective studies. However, methodological flaws and data errors invalidate both studies as credible evidence of risk. One showed reduced adverse events by half in T‑treated men but reversed this result using an unproven statistical approach. The authors subsequently acknowledged serious data errors including nearly 10% contamination of the dataset by women. The second study mistakenly used the rate of T prescriptions written by healthcare providers to men with recent myocardial infarction (MI) as a proxy for the naturally occurring rate of MI. Numerous studies suggest T is beneficial, including decreased mortality in association with TTh, reduced MI rate with TTh in men with the greatest MI risk prognosis, and reduced CV and overall mortality with higher serum levels of endogenous T. Randomized controlled trials have demonstrated benefits of TTh in men with coronary artery disease and congestive heart failure. Improvement in CV risk factors such as fat mass and glycemic control have been repeatedly demonstrated in T‑deficient men treated with T. The current evidence does not support the belief that TTh is associated with increased CV risk or CV mortality. On the contrary, a wealth of evidence accumulated over several decades suggests that low serum T levels are associated with increased risk and that higher endogenous T, as well as TTh itself, appear to be beneficial for CV mortality and risk.

  16. Antibiotic prophylaxis in primary immune deficiency disorders.

    Science.gov (United States)

    Kuruvilla, Merin; de la Morena, Maria Teresa

    2013-01-01

    Long-term prophylactic antibiotics are being widely implemented as primary or adjunctive therapy in primary immune deficiencies. This practice has transformed clinical outcomes in the setting of chronic granulomatous disease, complement deficiencies, Mendelian susceptibility to mycobacterial disease, Wiskott-Aldrich syndrome, hyper-IgE syndrome, Toll signaling defects, and prevented Pneumocystis in patients with T-cell deficiencies. Yet, controlled trials are few in the context of primary antibody deficiency syndromes, and most of this practice has been extrapolated from data in patients who are immune competent and with recurrent acute otitis media, chronic rhinosinusitis, cystic fibrosis, and bronchiectasis. The paucity of guidelines on the subject is reflected in recent surveys among practicing immunologists that highlight differences of habit regarding this treatment. Such discrepancies reinforce the lack of standard protocols on the subject. This review will provide evidence for the use of antibiotic prophylaxis in various primary immune deficiency populations, especially highlighting the role antibiotic prophylaxis in primary antibody deficiency syndromes. We also discussed the relationship of long-term antibiotic use and the prevalence of resistant pathogens. Overall, examination of available data on the use of prophylactic antibiotics in antibody deficiency syndromes merit future investigation in well-designed multicenter prospective trials because this population has few other management options.

  17. Reticulocyte maturity indices in iron deficiency anemia

    Directory of Open Access Journals (Sweden)

    Muriel Wollmann

    2014-01-01

    Full Text Available Objective: The aim of this study was to analyze the reticulocyte maturity indices (low, medium, and high fluorescence ratios in iron deficient 1- to 6-year-old children, and identify the prevalence of iron deficiency anemia in this population. Methods: The present study included 39 subjects, divided into two groups: control subjects (n = 33, and subjects with iron deficiency anemia (n = 6. The results were analyzed by Student's t-test for comparison of means. Differences were considered significant when two-tailed p-value < 0.05. Results: Subjects with iron deficiency anemia presented increases in the proportion of mean (10.3 ± 4.7% vs. 6.0 ± 3.4%; p-value = 0.003, and high fluorescence reticulocytes (2.3 ± 0.87% vs. 0.9 ± 0.9%; p-value = 0.03 compared to the control group. The prevalence of anemia in this population was 15% (n = 6. Conclusion: The indices related to immaturity of reticulocytes are higher in the presence of iron deficiency, thus demonstrating a deficiency in the raw material to form hemoglobin and are, therefore, possible early markers of iron deficiency and anemia. We emphasize the need to standardize these indices for use in clinical practice and lab test results.

  18. Perinatal iron deficiency and neurocognitive development

    Directory of Open Access Journals (Sweden)

    Emily Clare Radlowski

    2013-09-01

    Full Text Available 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. According to the World Health Organization, it affects nearly 2 billion people and up to 50% of women who are pregnant. Maternal anemia during pregnancy is especially burdensome to healthy neurodevelopment in the fetus because iron is needed for proper neurogenesis, development, and myelination. Maternal anemia also increases the risk of low birth weight, either due to premature birth or fetal growth restriction, which is associated with delayed neurocognitive development and even psychiatric illness. As rapid neurodevelopment continues after birth infants that received sufficient iron in utero, but that receive a low iron diet after 6 months of age, also show deficits in neurocognitive development, including impairments in learning and memory. Unfortunately, the neurocognitive complications of iron deficiency during critical pre- and postnatal periods of brain development are difficult to remedy, persisting into adulthood. Thus, preventing iron deficiency in the pre- and postnatal periods is critical as is devising new means to recapture cognitive function in individuals who experienced early iron deficiency. This review will discuss the prevalence of pre- and postnatal iron deficiency, the mechanism, and effects of iron deficiency on brain and cognitive development.

  19. Treatment of zinc deficiency without zinc fortification

    Institute of Scientific and Technical Information of China (English)

    Donald OBERLEAS; Barbara F. HARLAND

    2008-01-01

    Zinc (Zn) deficiency in animals became of interest until the 1950s. In this paper, progresses in researches on physi-ology of Zn deficiency in animals, phytate effect on bioavailability of Zn, and role of phytase in healing Zn deficiency of animals were reviewed. Several studies demonstrated that Zn is recycled via the pancreas; the problem of Zn deficiency was controlled by Zn homeostasis. The endogenous secretion of Zn is considered as an important factor influencing Zn deficiency, and the critical molar ratio is 10. Phytate (inositol hexaphosphate) constituted up to 90% of the organically bound phosphorus in seeds. Great improvement has been made in recent years on isolating and measuring phytate, and its structure is clear. Phytate is considered to reduce Zn bioavailability in animal. Phytase is the enzyme that hydrolyzes phytate and is present in yeast, rye bran, wheat bran, barley, triticale, and many bacteria and fungi. Zinc nutrition and bioavailability can be enhanced by addition of phytase to animal feeds. Therefore, using phytase as supplements, the most prevalent Zn deficiency in animals may be effectively corrected without the mining and smelting of several tons of zinc daily needed to correct this deficiency by fortification worldwide.

  20. Wound healing in Mac-1 deficient mice.

    Science.gov (United States)

    Chen, Lin; Nagaraja, Sridevi; Zhou, Jian; Zhao, Yan; Fine, David; Mitrophanov, Alexander Y; Reifman, Jaques; DiPietro, Luisa A

    2017-05-01

    Mac-1 (CD11b/CD18) is a macrophage receptor that plays several critical roles in macrophage recruitment and activation. Because macrophages are essential for proper wound healing, the impact of Mac-1 deficiency on wound healing is of significant interest. Prior studies have shown that Mac-1(-/-) mice exhibit deficits in healing, including delayed wound closure in scalp and ear wounds. This study examined whether Mac-1 deficiency influences wound healing in small excisional and incisional skin wounds. Three millimeter diameter full thickness excisional wounds and incisional wounds were prepared on the dorsal skin of Mac-1 deficient (Mac-1(-/-) ) and wild type (WT) mice, and wound healing outcomes were examined. Mac-1 deficient mice exhibited a normal rate of wound closure, generally normal levels of total collagen, and nearly normal synthesis and distribution of collagens I and III. In incisional wounds, wound breaking strength was similar for Mac-1(-/-) and WT mice. Wounds of Mac-1 deficient mice displayed normal total macrophage content, although macrophage phenotype markers were skewed as compared to WT. Interestingly, amounts of TGF-β1 and its downstream signaling molecules, SMAD2 and SMAD3, were significantly decreased in the wounds of Mac-1 deficient mice compared to WT. The results suggest that Mac-1 deficiency has little impact on the healing of small excisional and incisional wounds. Moreover, the findings demonstrate that the effect of single genetic deficiencies on wound healing may markedly differ among wound models. These conclusions have implications for the interpretation of the many prior studies that utilize a single model system to examine wound healing outcomes in genetically deficient mice. © 2017 by the Wound Healing Society.

  1. Hypopituitarism: growth hormone and corticotropin deficiency.

    Science.gov (United States)

    Capatina, Cristina; Wass, John A H

    2015-03-01

    This article presents an overview of adult growth hormone deficiency (AGHD) and corticotropin deficiency (central adrenal failure, CAI). Both conditions can result from various ailments affecting the hypothalamus or pituitary gland (most frequently a tumor in the area or its treatment). Clinical manifestations are subtle in AGHD but potentially life-threatening in CAI. The diagnosis needs dynamic testing in most cases. Treatment of AGHD is recommended in patients with documented severe deficiency, and treatment of CAI is mandatory in all cases. Despite significant progress in replacement hormonal therapy, more physiologic treatments and more reliable indicators of treatment adequacy are still needed.

  2. Growth hormone deficiency and hyperthermia during exercise

    DEFF Research Database (Denmark)

    Juul, A; Hjortskov, N; Jepsen, Leif

    1995-01-01

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

  3. Molecular genetics of human lactase deficiencies.

    Science.gov (United States)

    Järvelä, Irma; Torniainen, Suvi; Kolho, Kaija-Leena

    2009-01-01

    Lactase non-persistence (adult-type hypolactasia) is present in more than half of the human population and is caused by the down-regulation of lactase enzyme activity during childhood. Congenital lactase deficiency (CLD) is a rare severe gastrointestinal disorder of new-borns enriched in the Finnish population. Both lactase deficiencies are autosomal recessive traits and characterized by diminished expression of lactase activity in the intestine. Genetic variants underlying both forms have been identified. Here we review the current understanding of the molecular defects of human lactase deficiencies and their phenotype-genotype correlation, the implications on clinical practice, and the understanding of their function and role in human evolution.

  4. Nutrition and hair: deficiencies and supplements.

    Science.gov (United States)

    Finner, Andreas M

    2013-01-01

    Hair follicle cells have a high turnover. A caloric deprivation or deficiency of several components, such as proteins, minerals, essential fatty acids, and vitamins, caused by inborn errors or reduced uptake, can lead to structural abnormalities, pigmentation changes, or hair loss, although exact data are often lacking. The diagnosis is established through a careful history, clinical examination of hair loss activity, and hair quality and confirmed through targeted laboratory tests. Examples of genetic hair disorders caused by reduced nutritional components are zinc deficiency in acrodermatitis enteropathica and copper deficiency in Menkes kinky hair syndrome.

  5. Severe Vitamin D Deficiency Causing Kyphoscoliosis.

    Science.gov (United States)

    Singhai, Abhishek; Banzal, Subodh

    2013-01-01

    Vitamin D deficiency is common among Indian population. Women are especially at risk for severe vitamin D deficiency. The risk is higher for those who are multiparous and postmenopausal. Poor exposure to sunlight, higher latitude, winter season, inadequate diet, older age, obesity and malabsorption are also important risk factors. Symptoms of hypovitaminosis D, including diffuse or migratory pain affecting several sites (especially the shoulder, pelvis, ribcage and lower back) have also been misdiagnosed as musculoskeletal disorders, including fibromyalgia, polymyalgia rheumatica and ankylosing spondylitis. Here, we report two cases presented with kyphoscoliosis, diagnosed to have severe vitamin D deficiency.

  6. Growth hormone deficiency and hyperthermia during exercise

    DEFF Research Database (Denmark)

    Juul, A; Hjortskov, N; Jepsen, Leif

    1995-01-01

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

  7. Responses of Legumes to Phosphorus Deficiency

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    Phosphorus deficiency is a universal problem in most world soils. Furthermore, of all nutrients, shortage of phosphorus has the biggest impact on legumes, therefore, lots of studies were carried out for identifying responses of legumes to shortage of phosphorus. They concluded that to maintain improved growth under phosphorus deficiency conditions plants develop two major mechanisms: (i) Phosphorus acquisition (root morphology, root exudation and phosphorus uptake mechanisms), (ii) Phosphorus utilization (internal mechanisms associated with better use of absorbed phosphorus at cellular level). The aim of this brief review is to elucidate root morphological changes and rhizophere acidification to phosphorus deficiency.

  8. 21-Hydroxylase deficiency in Brazil

    Directory of Open Access Journals (Sweden)

    T.A.S.S. Bachega

    2000-10-01

    Full Text Available We determined the frequency of large rearrangements and point mutations in 130 Brazilian patients with 21-hydroxylase deficiency and correlated genotype with phenotype. The frequency of CYP21 deletions was lower (4.4% than in most of the previous series described, whereas the frequency of large gene conversions was similar to the frequency reported in the literature (6.6%. The most frequent point mutations were I2 splice (41.8% in salt wasting - SW, I172N (32.6% in simple virilizing - SV and V281L (40.2% in the late onset form - LO. The frequency of the nine most common point mutations was similar to that reported for other countries. The 93 fully genotyped patients were classified into 3 mutation groups based on the degree of enzymatic activity (A@ 2%, C>20%. In group A, 62% of cases presented the SW form; in group B, 96% the SV form, and in group C, 88% the LO form. We diagnosed 80% of the affected alleles after screening for large rearrangements and 15 point mutations. To diagnose these remaining alleles we sequenced the CYP21 gene of one patient with the SV form and identified a heterozygous G->A transition in codon 424. This mutation leads to a substitution of glycine by serine in a conserved region and was also found in a compound heterozygous state in 4 other patients. The mutation G424S presented a linkage disequilibrium with CYP21P and C4A gene deletions and HLA DR17, suggesting a probable founder effect. Search for the G424S mutation in other populations will reveal if it is restricted to the Brazilian patients or if it has a wider ethnic distribution.

  9. CBS c.844ins68 Polymorphism Frequencies in Control Populations: Implications on Nonsyndromic Cleft Lip With or Without Cleft Palate.

    Science.gov (United States)

    Murthy, Jyotsna; Lakkakula, Saikrishna; Gurramkonda, Venkatesh Babu; Pathapati, Ram Mohan; Maram, Rajasekhar; Lakkakula, Bhaskar V K S

    2015-01-01

    Nonsyndromic cleft lip with or without cleft palate (NSCLP) is a common birth defect with substantial clinical and social impact. Folate deficiency is one of the factors that have been associated with increased risk for NSCLP. Polymorphisms in folate and homocysteine pathway genes may act as susceptibility factors. The objective of this study was to evaluate prevalence estimates of cystathionine beta-synthase (CBS) insertion of 68-bp (c.844ins68) polymorphisms and their correlation with NSCLP. A total of 236 unrelated individuals from seven Indian populations and an additional 355 cases with NSCLP and 357 controls without NSCLP were included in this study. We investigated the CBS c.844ins68 polymorphism in all samples. Genotyping was performed with polymerase chain reaction and electrophoresis. The data were statistically analyzed using the chi-square test. The CBS c.844ins68 allele is present in six of the seven populations analyzed, and allele frequencies range from 1.5% in Balija to 9.1% in Sugali populations. The CBS c.844ins68 polymorphism showed a significant protective effect on NSCLP at both genotype (WW versus WI: odds ratio [OR] = 0.54, 95% confidence interval [CI] = 0.31 to 0.95, P = .149) and allele levels (W versus I: OR = 0.56, 95% CI = 0.32 to 0.96, P = .033). The current study observed significant differences in the frequency of the CBS 844ins68 allele across populations. There is a significant association between CBS c.844ins68 polymorphism and cleft lip and palate in the Indian population. Additional studies are warranted to identify the functional variants in the genes controlling homocysteine as etiological contributors to the formation of oral clefts.

  10. Homocysteine induces energy imbalance in rat skeletal muscle: is creatine a protector?

    Science.gov (United States)

    Kolling, Janaína; Scherer, Emilene B S; Siebert, Cassiana; Hansen, Fernanda; Torres, Felipe V; Scaini, Giselli; Ferreira, Gabriela; de Andrade, Rodrigo B; Gonçalves, Carlos A S; Streck, Emílio L; Wannmacher, Clovis M D; Wyse, Angela T S

    2013-10-01

    Homocystinuria is a neurometabolic disease caused by a severe deficiency of cystathionine beta-synthase activity, resulting in severe hyperhomocysteinemia. Affected patients present several symptoms including a variable degree of motor dysfunction. In this study, we investigated the effect of chronic hyperhomocysteinemia on the cell viability of the mitochondrion, as well as on some parameters of energy metabolism, such as glucose oxidation and activities of pyruvate kinase, citrate synthase, isocitrate dehydrogenase, malate dehydrogenase, respiratory chain complexes and creatine kinase in gastrocnemius rat skeletal muscle. We also evaluated the effect of creatine on biochemical alterations elicited by hyperhomocysteinemia. Wistar rats received daily subcutaneous injections of homocysteine (0.3-0.6 µmol/g body weight) and/or creatine (50 mg/kg body weight) from the 6th to the 28th days of age. The animals were decapitated 12 h after the last injection. Homocysteine decreased the cell viability of the mitochondrion and the activities of pyruvate kinase and creatine kinase. Succinate dehydrogenase was increased other evaluated parameters were not changed by this amino acid. Creatine, when combined with homocysteine, prevented or caused a synergistic effect on some changes provoked by this amino acid. Creatine per se or creatine plus homocysteine altered glucose oxidation. These findings provide insights into the mechanisms by which homocysteine exerts its effects on skeletal muscle function, more studies are needed to elucidate them. Although creatine prevents some alterations caused by homocysteine, it should be used with caution, mainly in healthy individuals because it could change the homeostasis of normal physiological functions.

  11. Creatine prevents the imbalance of redox homeostasis caused by homocysteine in skeletal muscle of rats.

    Science.gov (United States)

    Kolling, Janaína; Scherer, Emilene B S; Siebert, Cassiana; Marques, Eduardo Peil; Dos Santos, Tiago Marcom; Wyse, Angela T S

    2014-07-15

    Homocystinuria is a neurometabolic disease caused by severe deficiency of cystathionine beta-synthase activity, resulting in severe hyperhomocysteinemia. Affected patients present several symptoms including a variable degree of motor dysfunction, being that the pathomechanism is not fully understood. In the present study we investigated the effect of chronic hyperhomocysteinemia on some parameters of oxidative stress, namely 2'7'dichlorofluorescein (DCFH) oxidation, levels of thiobarbituric acid-reactive substances (TBARS), antioxidant enzyme activities (SOD, CAT and GPx), reduced glutathione (GSH), total sulfhydryl and carbonyl content, as well as nitrite levels in soleus skeletal muscle of young rats subjected to model of severe hyperhomocysteinemia. We also evaluated the effect of creatine on biochemical alterations elicited by hyperhomocysteinemia. Wistar rats received daily subcutaneous injection of homocysteine (0.3-0.6 μmol/g body weight), and/or creatine (50mg/kg body weight) from their 6th to the 28th days age. Controls and treated rats were decapitated at 12h after the last injection. Chronic homocysteine administration increased 2'7'dichlorofluorescein (DCFH) oxidation, an index of production of reactive species and TBARS levels, an index of lipoperoxidation. Antioxidant enzyme activities, such as SOD and CAT were also increased, but GPx activity was not altered. The content of GSH, sulfhydril and carbonyl were decreased, as well as levels of nitrite. Creatine concurrent administration prevented some homocysteine effects probably by its antioxidant properties. Our data suggest that the oxidative insult elicited by chronic hyperhomocystenemia may provide insights into the mechanisms by which homocysteine exerts its effects on skeletal muscle function. Creatine prevents some alterations caused by homocysteine.

  12. Molecular genetic analysis of pyridoxine-nonresponsive homocystinuric siblings with different blood methionine levels during the neonatal period.

    Science.gov (United States)

    Chen, S; Ito, M; Saijo, T; Naito, E; Kuroda, Y

    1999-08-01

    Two mutations in the cystathionine beta-synthase (CBS) gene were found in two Japanese siblings with pyridoxine non-responsive homocystinuria who had different methionine levels in their blood during the neonatal period. Both patients were compound heterozygotes of two mutant alleles: one had an A-to-G transition at nucleotide 194 (A194 G) that caused a histidine-to-arginine substitution at position 65 of the protein (H65R), while the other had a G-to-A transition at nucleotide 346 (G346A) which resulted in a glycine-to-arginine substitution at position 116 of the protein (G116R). The two mutant proteins were separately expressed in Escherichia coli, and they completely lacked catalytic activity. Despite their identical genotypes and almost equal protein intake, these siblings showed different levels of blood methionine during the neonatal period, suggesting that the level of methionine in blood is determined not only by the defect in the CBS gene and protein intake, but also by the activity of other enzymes involved in methionine and homocysteine metabolism, especially during the neonatal period. Therefore, high-risk newborns who have siblings with homocystinuria, even if the level of methionine in their blood is normal in a neonatal mass screening, should be followed up and diagnosed by an assay of enzyme activity or a gene analysis so that treatment can be begun as soon as possible to prevent the development of clinical symptoms. In addition, a new, more sensitive method for the mass screening of CBS deficiency in neonates should be developed.

  13. PREVALENCE AND SEVERITY OF IODINE DEFICIENCY ...

    African Journals Online (AJOL)

    GB

    2012-11-03

    Nov 3, 2012 ... that severe iodine deficiency in Ethiopian women leads to 50,000 ... there will be hypothyroidism that causes low metabolic ... high in pregnant mothers and in school children as evidenced by research articles. Especially in.

  14. Vitamin D deficiency in pediatric critical illness

    Directory of Open Access Journals (Sweden)

    Kiran B. Hebbar, MD, FCCM

    2014-12-01

    Conclusions: Vitamin D deficiency is common in the pediatric critical care population. Significant seasonal differences were noted even in the critically ill. The role of vitamin D in certain diseases like asthma in critically ill children merit further study.

  15. Isoprenoid biosynthesis and mevalonate kinase deficiency

    NARCIS (Netherlands)

    Henneman, L.

    2011-01-01

    Mevalonaat Kinase Deficiëntie (MKD) is een aangeboren ziekte geassocieerd met heftige koortsaanvallen die drie tot vier dagen aanhouden en gepaard gaan met koude rillingen, gewrichtsklachten, huiduitslag, hoofdpijn, duizeligheid, buikpijn, braken en diarree. De koortsaanvallen treden gemiddeld eens

  16. PREVALENCE AND SEVERITY OF IODINE DEFICIENCY ...

    African Journals Online (AJOL)

    GB

    2012-11-03

    Nov 3, 2012 ... BACKGROUND: Iodine deficiency disorder is a major problem worldwide, .... method involves the titration of a solution of salt ..... blocks the thyroid peroxidase enzyme (29, 34). .... Modern Nutrition in Health and Disease, Lea.

  17. Genetics Home Reference: mitochondrial trifunctional protein deficiency

    Science.gov (United States)

    ... link) ACT Sheet: Elevated C16-OH +/- C18:1-OH and Other Long Chain Acylcarnitines (PDF) Genetic Testing (1 link) Genetic Testing Registry: Mitochondrial trifunctional protein deficiency Other Diagnosis and Management Resources (3 links) ...

  18. Genetics Home Reference: guanidinoacetate methyltransferase deficiency

    Science.gov (United States)

    ... Facebook Share on Twitter Your Guide to Understanding Genetic Conditions Search MENU Toggle navigation Home Page Search ... Conditions Genes Chromosomes & mtDNA Resources Help Me Understand Genetics Home Health Conditions guanidinoacetate methyltransferase deficiency guanidinoacetate methyltransferase ...

  19. Genetics Home Reference: GM3 synthase deficiency

    Science.gov (United States)

    ... Facebook Share on Twitter Your Guide to Understanding Genetic Conditions Search MENU Toggle navigation Home Page Search ... Conditions Genes Chromosomes & mtDNA Resources Help Me Understand Genetics Home Health Conditions GM3 synthase deficiency GM3 synthase ...

  20. Impulsivity: A deficiency of inhibitory control?

    NARCIS (Netherlands)

    Lansbergen, M.M.

    2007-01-01

    Impulsivity has been defined as acting without thinking. Impulsivity can be quantified by impulsivity questionnaires, but also by behavioral paradigms which tax inhibitory control. Previous research has repeatedly demonstrated deficient inhibitory control in psychopathological samples characterized

  1. Genetics Home Reference: familial lipoprotein lipase deficiency

    Science.gov (United States)

    ... Rare Disorders (NORD) RareConnect GeneReviews (1 link) Familial Lipoprotein Lipase Deficiency ClinicalTrials.gov (1 link) ClinicalTrials.gov Scientific Articles on PubMed (1 link) PubMed OMIM (1 link) ...

  2. Vitamin K deficiency bleeding of the newborn

    Science.gov (United States)

    Vitamin K deficiency bleeding of the newborn (VKDB) is a bleeding disorder in babies. It most often ... A lack of vitamin K may cause severe bleeding in newborn babies. Vitamin K plays an important role in blood clotting. Babies often ...

  3. Iron-Deficiency Anemia and Stroke

    OpenAIRE

    J Gordon Millichap

    2007-01-01

    The prevalence of iron-deficiency anemia (IDA) in young children at the time of stroke and in age-matched healthy controls was compared in a case-control study conducted at the Hospital for Sick Children, Toronto, Canada.

  4. Genetics Home Reference: glutamate formiminotransferase deficiency

    Science.gov (United States)

    ... glutamate formiminotransferase deficiency is also characterized by megaloblastic anemia. Megaloblastic anemia occurs when a person has a low number ... named? Additional Information & Resources MedlinePlus (4 ... Encyclopedia: Megaloblastic Anemia (image) Health Topic: Amino Acid Metabolism Disorders Health ...

  5. VITAMIN A DEFICIENCY IN NIGERIAN CHILDREN

    African Journals Online (AJOL)

    Dr Olaleye

    Keywords: Vitamin A deficiency, Nigeria, Children. INTRODUCTION. Vitamin A ... related illness when the diet is supplemented with. Vitamin A. This .... rates of 49.6% and 48.6% respectively. The prevalence .... Bangladesh. J. Trop. Paediatr.

  6. Genetics Home Reference: dihydropyrimidine dehydrogenase deficiency

    Science.gov (United States)

    ... of the skin on the palms and soles (hand-foot syndrome); shortness of breath; and hair loss may also ... dehydrogenase deficiency , with its early-onset neurological symptoms, is a rare disorder. Its prevalence is ...

  7. Genetics Home Reference: phosphoglycerate mutase deficiency

    Science.gov (United States)

    ... production in these cells. This defect underlies the muscle cramping and myoglobinuria that occur after strenuous exercise in ... phosphoglycerate mutase deficiency , including episodes of exercise-induced muscle cramping and myoglobinuria. Related Information What does it mean ...

  8. Iron Deficiency, Zinc, Magnesium, Vitamin Deficiencies in Crohn's Disease: Substitute or Not?

    Science.gov (United States)

    Kruis, Wolfgang; Phuong Nguyen, G

    2016-01-01

    Inflammatory bowel disease (IBD) is characterized by inflammatory reactions, complications, extraintestinal manifestations and a loss of intestinal functions, for example, failures of absorption and secretion. According to intestinal dysfunction, a wide array of pathogenetic pathways is existing leading to iron deficiency and numerous vitamins as well as trace element deficiencies. Complications, symptoms and signs of those deficiencies are common in IBD with varying degrees of clinical significance. This review focuses on selected micronutrients including iron, zinc, magnesium and some vitamins. Epidemiology with respect to IBD, pathophysiology, diagnosis and clinical aspects are addressed. Finally, some suggestions for treatment of deficient situations are discussed. In conclusion, some micronutrients have significant impact on complications and quality of life in IBD. Deficiencies may even influence the course of the disease. Those deficiencies should be thoroughly supplemented.

  9. New mechanism of lipotoxicity in diabetic cardiomyopathy: Deficiency of Endogenous H2S Production and ER stress.

    Science.gov (United States)

    Guo, Runmin; Wu, Zijun; Jiang, Jiamei; Liu, Chang; Wu, Bin; Li, Xingyue; Li, Teng; Mo, Hailiang; He, Songjian; Li, Shanghai; Yan, Hai; Huang, Ruina; You, Qiong; Wu, Keng

    2017-03-01

    To investigate the roles and mechanisms of endogenous hydrogen sulfide (H2S) and endoplasmic reticulum (ER) stress in the development of diabetic cardiomyopathy (DCM). Blood of DCM patients included in the study were collected. The model of DCM rats was established using streptozotocin (STZ) injection. Cardiac lipotoxicity in vitro models were established using 500μM palmitic acid (PA) treatment for 24h in AC16 cardiomyocytes. Endogenous H2S production in plasma, culture supernatant and heart was measured by sulphur ion-selective electrode assay. Cell viability was tested by using the cell counting kit-8 (CCK-8) kit. Glucose regulated protein (GRP78), CCAAT/enhancer binding protein homologous transcription factor (C/EBP) homologous protein (CHOP), caspase-3 and caspase-12 expressions were measured using western blot analysis. Lipid droplet was evaluated by Oil Red O staining. Apoptosis in hearts of DCM rats was analyzed using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. H2S levels in serum of DCM patients and DCM rats were significant lower, H2S contents and cystathionine-γ-lyase (CSE) expression in heart tissues of DCM rats were also markedly lower. H2S levels in supernatants of PA-treated AC16 cardiac cells were decreased. Cardiac lipotoxicity demonstrated by increase in TUNEL positive cells and lipid deposit in vivo and in vitro accompanied by a decrease of H2S levels. Pretreatment AC16 cells with 100μmol/L of NaHS (a donor of H2S) could suppress the PA-induced myocardial injury similar to the effects of 4-phenylbutyric acid (4-PBA, an endoplasmic reticulum (ER) stress inhibitor), leading to an increase in cell viability and preventing lipid deposit. Meanwhile, administration diabetic rats with NaHS or 4-PBA alleviated cardiac lipotoxicity, as evidenced by decrease in TUNEL positive cells, cleaved caspase-3 expression and lipid accumulation. Deficiency of endogenous H2S was involved in lipotoxicity-induced myocardial injury

  10. Dietary restriction causing iodine-deficient goitre.

    Science.gov (United States)

    Cheetham, Tim; Plumb, Emma; Callaghan, James; Jackson, Michael; Michaelis, Louise

    2015-08-01

    Iodine-deficient goitre was common in some parts of the UK prior to the introduction of salt iodisation. Many contemporary salt preparations do not contain much iodine, and there are renewed concerns about the iodine status of the population. We present a boy with severe allergy who developed goitre and significant thyroid dysfunction in association with an iodine-deficient 'food-restricted' diet. The case highlights the importance of a comprehensive nutritional assessment in all children on multiple food restrictions.

  11. [Nutritive correction and iodine deficiency in children].

    Science.gov (United States)

    Shilina, N M; Pozdniakov, A L

    2007-01-01

    It is well known that deficiency of calcium and iodine--essential food components needed for children's valuable growth and development--is observed presently in children of different age. Considering this fact, the "Danone" company together with Institute of Nutrition (Russia) has developed a special formula, including calcium, iodine and vitamin D, for dairy products "Rastishka". The use of these products facilitates both reducing the risk of the above mentioned microelement deficiency and children's growth and development.

  12. Environmental controls on iodine deficiency disorders (IDD)

    OpenAIRE

    Johnson, C C; Fordyce, F.M.

    2003-01-01

    It is estimated that in excess of one billion people world-wide are at risk from iodine deficiency disorders (IDD), the most obvious manifestation of which is goitre (see Fordyce, 2000). Iodine deficiency is the world’s most common cause of mental retardation and brain damage, and the negative effects of impaired mental function have a significant impact on the social and economic development of communities. Although IDD can be caused by a number of factors, goitrogens fo...

  13. Severe Vitamin D Deficiency Causing Kyphoscoliosis

    OpenAIRE

    Singhai, Abhishek; Banzal, Subodh

    2013-01-01

    Vitamin D deficiency is common among Indian population. Women are especially at risk for severe vitamin D deficiency. The risk is higher for those who are multiparous and postmenopausal. Poor exposure to sunlight, higher latitude, winter season, inadequate diet, older age, obesity and malabsorption are also important risk factors. Symptoms of hypovitaminosis D, including diffuse or migratory pain affecting several sites (especially the shoulder, pelvis, ribcage and lower back) have also been ...

  14. Colour vision deficiency and physics teaching

    Science.gov (United States)

    Maule, Louise; Featonby, David

    2016-05-01

    1 in 12 males suffer from some form of colour vision deficiency (CVD) which in the present colour dominated world of education presentation can be a severe disadvantage. Although aware of ‘colourblindness’ most teachers make little or no adjustment for these pupils for whom tasks may be more difficult. This article examines colour vision deficiency and looks at ways in which we can help the many students who have this problem.

  15. Androgen deficiency and metabolic syndrome in men

    OpenAIRE

    Winter, Ashley G; Zhao, Fujun; Lee, Richard K.

    2014-01-01

    Metabolic syndrome (MetS) is a growing health concern worldwide. Initially a point of interest in cardiovascular events, the cluster of HTN, obesity, dyslipidemia, and insulin resistance known as MetS has become associated with a variety of other disease processes, including androgen deficiency and late-onset hypogonadism (LOH). Men with MetS are at a higher risk of developing androgen deficiency, and routine screening of testosterone (T) is advised in this population. The pathophysiology of ...

  16. Cushing, acromegaly, GH deficiency and tendons

    OpenAIRE

    2014-01-01

    Cushing’s syndrome, induced by an endogenous or exogenous cortisol excess, and acromegaly, the clinical syndrome caused by growth hormone (GH) excess in adulthood, as well as the disease induced by GH deficiency (GHD), represent perfect models for the evaluation of the effects induced by chronic exposure in vivo, respectively, to cortisol and GH/IGF-1 excess or deficiency on the complex structure of the tendons as well as on the related post-traumatic repair mechanism. Although the literature...

  17. Anemia and iron deficiency in heart failure.

    Science.gov (United States)

    Gil, Victor M; Ferreira, Jorge S

    2014-01-01

    Heart failure is a common problem and a major cause of mortality, morbidity and impaired quality of life. Anemia is a frequent comorbidity in heart failure and further worsens prognosis and disability. Regardless of anemia status, iron deficiency is a common and usually unidentified problem in patients with heart failure. This article reviews the mechanisms, impact on outcomes and treatment of anemia and iron deficiency in patients with heart failure.

  18. Targeting Iron Deficiency Anemia in Heart Failure.

    Science.gov (United States)

    Saraon, Tajinderpal; Katz, Stuart D

    2016-01-01

    Iron deficiency is common in heart failure (HF) patients, and is associated with increased risk of adverse clinical outcomes. Clinical trials of intravenous iron supplementation in iron-deficient HF patients have demonstrated short-term improvement in functional capacity and quality of life. In some trials, the benefits of iron supplementation were independent of the hemoglobin levels. Additional investigations of iron supplementation are needed to characterize the mechanisms contributing to clinical benefit and long-term safety in HF.

  19. Deficiently Extremal Cohen-Macaulay Algebras

    Indian Academy of Sciences (India)

    Chanchal Kumar; Pavinder Singh

    2010-04-01

    The aim of this paper is to study homological properties of deficiently extremal Cohen–Macaulay algebras. Eagon–Reiner showed that the Stanley–Reisner ring of a simplicial complex has a linear resolution if and only if the Alexander dual of the simplicial complex is Cohen–Macaulay. An extension of a special case of Eagon–Reiner theorem is obtained for deficiently extremal Cohen–Macaulay Stanley–Reisner rings.

  20. Iron deficiency or anemia of inflammation?

    OpenAIRE

    Nairz, Manfred; Theurl, Igor; Wolf, Dominik; Weiss, Günter

    2016-01-01

    Summary Iron deficiency and immune activation are the two most frequent causes of anemia, both of which are based on disturbances of iron homeostasis. Iron deficiency anemia results from a reduction of the body’s iron content due to blood loss, inadequate dietary iron intake, its malabsorption, or increased iron demand. Immune activation drives a diversion of iron fluxes from the erythropoietic bone marrow, where hemoglobinization takes place, to storage sites, particularly the mononuclear ph...

  1. Tob deficiency superenhances osteoblastic activity after ovariectomy to block estrogen deficiency-induced osteoporosis

    OpenAIRE

    Usui, Michihiko; Yoshida, Yutaka; Tsuji, Kunikazu; OIKAWA, kaoru; Miyazono, Kohei; Ishikawa, Isao; YAMAMOTO, Tadashi; Nifuji, Akira; Noda, Masaki

    2004-01-01

    Tob (transducer of erbB2) is a member of antiproliferative family proteins and acts as a bone morphogenic protein inhibitor as well as a suppressor of proliferation in T cells, which have been implicated in postmenopausal bone loss. To determine the effect of Tob deficiency on estrogen deficiency-induced bone loss, we analyzed bone metabolism after ovariectomy or sham operation in Tob-deficient mice. Ovariectomy in WT mice decreased trabecular bone volume and bone mineral density (BMD) as exp...

  2. [Approaches to vitamin B12 deficiency].

    Science.gov (United States)

    Russcher, Henk; Heil, Sandra G; Slobbe, Lennert; Lindemans, Jan

    2012-01-01

    A 28-year-old female vegetarian was referred to a specialist in internal medicine with persistent iron deficiency. Laboratory analysis revealed microcytic anaemia with low ferritin levels but normal total vitamin B12 levels. The red blood cell distribution width, however, showed a very wide variation in red blood cell sizes, indicating a coexisting vitamin B12 deficiency, which was confirmed by the low concentration of active vitamin B12. Another patient, a 69-year-old woman with a history of previous gastric surgery and renal insufficiency as a complication of diabetes mellitus, was suspected to be deficient in vitamin B12, as she had low total vitamin B12 levels and an accumulation of methylmalonic acid and homocysteine in her blood. Testing the total concentration of vitamin B12 alone has insufficient diagnostic accuracy and no accepted gold standard is available for diagnosing vitamin B12 deficiency. With the development of newer tests, such as measuring holotranscobalamin II (concentration of active vitamin B12), atypical and subclinical deficiency states can be recognized. A new approach to diagnosing vitamin B12 deficiency is presented, based upon these 2 case descriptions.

  3. Recognition and management of vitamin D deficiency.

    Science.gov (United States)

    Bordelon, Paula; Ghetu, Maria V; Langan, Robert C

    2009-10-15

    Vitamin D deficiency affects persons of all ages. Common manifestations of vitamin D deficiency are symmetric low back pain, proximal muscle weakness, muscle aches, and throbbing bone pain elicited with pressure over the sternum or tibia. A 25-hydroxyvitamin D level should be obtained in patients with suspected vitamin D deficiency. Deficiency is defined as a serum 25-hydroxyvitamin D level of less than 20 ng per mL (50 nmol per L), and insufficiency is defined as a serum 25-hydroxyvitamin D level of 20 to 30 ng per mL (50 to 75 nmol per L). The goal of treatment is to normalize vitamin D levels to relieve symptoms and decrease the risk of fractures, falls, and other adverse health outcomes. To prevent vitamin D deficiency, the American Academy of Pediatrics recommends that infants and children receive at least 400 IU per day from diet and supplements. Evidence shows that vitamin D supplementation of at least 700 to 800 IU per day reduces fracture and fall rates in adults. In persons with vitamin D deficiency, treatment may include oral ergocalciferol (vitamin D2) at 50,000 IU per week for eight weeks. After vitamin D levels normalize, experts recommend maintenance dosages of cholecalciferol (vitamin D3) at 800 to 1,000 IU per day from dietary and supplemental sources.

  4. An Approach to Iron-Deficiency Anemia

    Directory of Open Access Journals (Sweden)

    Imran Rasul

    2001-01-01

    Full Text Available Iron-deficiency anemia is a common reason for referral to a gastroenterologist. In adult men and postmenopausal women, gastrointestinal tract pathology is often the cause of iron-deficiency anemia, so patients are frequently referred for endoscopic evaluation. Endoscopy may be costly and at times difficult for the patient. Therefore, physicians need to know what lesions can be identified reliably and, more importantly, the importance of ruling out life-threatening conditions such as occult malignancy. Over the past decade, a number of prospective studies have been completed that examined the yield of endoscopy in the investigation of iron-deficiency anemia. The present article provides a broad overview of iron-deficiency anemia, with particular emphasis on hematological diagnosis, etiology, the use of endoscopy in identifying lesions and iron-repletion therapy. Other clinical scenarios, including assessment of patients on anti-inflammatory or anticoagulation therapy and patients with bleeding of obscure origin, are also addressed. The present article provides a diagnostic algorithm to iron-deficiency anemia, which describes a more systematic manner in which to approach iron-deficiency anemia.

  5. Hydrogen sulfide in gastrointestinal and liver physiopathology.

    Science.gov (United States)

    Cipriani, Sabrina; Mencarelli, Andrea

    2011-04-01

    Hydrogen sulfide (H(2)S) is a gas that can be formed by the action of two enzymes, cystathionine gamma lyase (CSE) and cystathionine beta synthase (CBS). H(2)S has been known for hundreds of years for its poisoning effect, however the idea that H(2)S is not only a poison, but can exert a physiological role in mammalian organisms, originates from the evidence that this gaseous mediator is produced endogenously. In addition to H(2)S synthesis by gastrointestinal tissue, the intestinal mucosa, particularly in the large intestine, is regularly exposed to high concentrations of H(2)S that are generated by some species of bacteria and through the reduction of unabsorbed intestinal inorganic sulphate. This review reports on the effects of H(2)S in the gastrointestinal tract and liver and provides information on the therapeutic applications of H(2)S-donating drugs.

  6. Brain hydrogen sulfide is severely decreased in Alzheimer's disease.

    Science.gov (United States)

    Eto, Ko; Asada, Takashi; Arima, Kunimasa; Makifuchi, Takao; Kimura, Hideo

    2002-05-24

    Although hydrogen sulfide (H2S) is generally thought of in terms of a poisonous gas, it is endogenously produced in the brain from cysteine by cystathionine beta-synthase (CBS). H2S functions as a neuromodulator as well as a smooth muscle relaxant. Here we show that the levels of H2S are severely decreased in the brains of Alzheimer's disease (AD) patients compared with the brains of the age matched normal individuals. In addition to H2S production CBS also catalyzes another metabolic pathway in which cystathionine is produced from the substrate homocysteine. Previous findings, which showed that S-adenosyl-l-methionine (SAM), a CBS activator, is much reduced in AD brain and that homocysteine accumulates in the serum of AD patients, were confirmed. These observations suggest that CBS activity is reduced in AD brains and the decrease in H2S may be involved in some aspects of the cognitive decline in AD.

  7. Lower limb deficient children in the Netherlands : epidemiological aspects

    NARCIS (Netherlands)

    Rijnders, LJM; Boonstra, AM; Groothoff, JW; Cornel, MC; Eisma, WH

    2000-01-01

    information on the characteristics of children with limb deficiencies and amputations in the Netherlands is largely lacking. The present study aimed to collect data about the prevalence of congenital deficiencies, the ratio of congenital to acquired limb deficiencies, types of lower leg deficiency o

  8. 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

  9. Paraoxonase and arylesterase activities in children with iron deficiency anemia and vitamin B12 deficiency anemia.

    Science.gov (United States)

    Koc, Ahmet; Cengiz, Murad; Ozdemir, Zeynep Canan; Celik, Hakim

    2012-05-01

    Paraoxonase-1 is an esterase enzyme and it has 3 types of activity, namely paraoxonase, arylesterase, and diazoxonase. It has been reported that paraoxonase-1 deficiency is related to increased susceptibility to development of atherosclerosis and cardiovascular disease. The aim of this study was to investigate serum paraoxonase and arylesterase activities in children with iron deficiency anemia and vitamin B(12) deficiency anemia. Thirty children with iron deficiency anemia, 30 children with vitamin B(12) deficiency anemia, and 40 healthy children aged 6 months to 6 years were enrolled in this study. Serum paraoxonase and arylesterase activities were measured with a spectrophotometer by using commercially available kits. Mean paraoxonase and arylesterase activities in vitamin B(12) deficiency anemia group (103 ± 73 and 102 ± 41 U/L, respectively) were significantly lower than mean activities of control group (188 ± 100 and 147 ± 34 U/L, respectively; P iron deficiency anemia group (165 ± 103 and 138 ± 39 U/L, respectively; P iron deficiency anemia and control groups (P > .05). Paraoxonase and arylesterase activities significantly increased after treatment with vitamin B(12) in vitamin B(12) deficiency anemia; however, there were no significant changes in the activities of these enzymes after iron treatment in iron deficiency anemia group. Important correlations were found between vitamin B(12) levels and both paraoxonase and arylesterase activities (r = .367, P deficiency anemia causes important reductions in paraoxonase and arylesterase activities, and after vitamin B(12) therapy the activities of these enzymes returned to near-normal levels.

  10. Complement genetics, deficiencies, and disease associations.

    Science.gov (United States)

    Mayilyan, Karine R

    2012-07-01

    The complement system is a key component of innate immunity. More than 45 genes encoding the proteins of complement components or their isotypes and subunits, receptors, and regulators have been discovered. These genes are distributed throughout different chromosomes, with 19 genes comprising three significant complement gene clusters in the human genome. Genetic deficiency of any early component of the classical pathway (C1q, C1r/s, C2, C4, and C3) is associated with autoimmune diseases due to the failure of clearance of immune complexes (IC) and apoptotic materials, and the impairment of normal humoral response. Deficiencies of mannan-binding lectin (MBL) and the early components of the alternative (factor D, properdin) and terminal pathways (from C3 onward components: C5, C6, C7, C8, C9) increase susceptibility to infections and their recurrence. While the association of MBL deficiency with a number of autoimmune and infectious disorders has been well established, the effects of the deficiency of other lectin pathway components (ficolins, MASPs) have been less extensively investigated due to our incomplete knowledge of the genetic background of such deficiencies and the functional activity of those components. For complement regulators and receptors, the consequences of their genetic deficiency vary depending on their specific involvement in the regulatory or signalling steps within the complement cascade and beyond. This article reviews current knowledge and concepts about the genetic load of complement component deficiencies and their association with diseases. An integrative presentation of genetic data with the latest updates provides a background to further investigations of the disease association investigations of the complement system from the perspective of systems biology and systems genetics.

  11. [Diagnostic criteria for vitamin D-deficient rickets and hypocalcemia-].

    Science.gov (United States)

    Ozono, Keiichi

    2016-02-01

    Vitamin D deficiency causes rickets or osteomalacia, which is associated with hypomineralization of bone and chondrocytes, and/or hypocalcemia. Accumulating evidence indicates increase in frequency of vitamin D deficiency due to insufficient intake of vitamin D and calcium and decrease in sunshine. It is necessary for clinician to diagnose vitamin D deficiency accurately and treat patients with vitamin D deficiency adequately. For the purpose, clinical guideline or expert opinion on vitamin D deficiency has been reported.

  12. Dietary iodine deficiency in the Gippsland region of Victoria, Australia

    OpenAIRE

    Rahman, Mohammad Ashequr

    2017-01-01

    Background Iodine is an essential micronutrient for the production of thyroid hormones and normal neurodevelopment. A deficiency in iodine causes a number of defects collectively known as Iodine Deficiency Disorder (IDD). Even mild iodine deficiency in pregnancy is a risk factor for babies as it may result in impaired intellectual development; this is the most serious consequence of mild to moderate dietary iodine deficiency. Australia overall is iodine deficient. However, in the Nationa...

  13. Iron deficiency anemia from diagnosis to treatment in children

    OpenAIRE

    Özdemir, Nihal

    2015-01-01

    Iron deficiency is the most common nutritional deficiency worldwide and an important public health problem especially in developing countries. Since the most important indicator of iron deficieny is anemia, the terms “iron deficiency” and “iron deficiency anemia” are often used interchangeably. However, iron deficiency may develop in the absence of anemia and the tissues may be affected from this condition. The most common causes of iron deficiency in children include insufficient intake toge...

  14. Experimental Copper Deficiency, Chromium Deficiency and Additional Molybdenum Supplementation in Goats – Pathological Findings

    Directory of Open Access Journals (Sweden)

    Frank A

    2001-09-01

    Full Text Available Secondary copper (Cu deficiency, chromium (Cr deficiency and molybdenosis (Mo has been suggested to cause the "mysterious" moose disease in the southwest of Sweden. The present experiment was performed on goats to investigate the clinical, chemical, and pathological alterations after 20 months feeding of a semi-synthetic diet deficient in Cu and Cr. Four groups were included in the study: control group (n = 4, Cu-deficient group (group 1, n = 4, Cr-deficient group (group 2, n = 2 and Cu+Cr-deficient group (group 3, n = 3. Group 3 was additionally supplemented with tetrathiomolybdate during the last 2 months of the experiment. Main histopathological findings in groups 1 and 3 were the lesions in the liver, characterised by a severe active fibrosis, bile duct proliferation, haemosiderosis and mild necroses. Additionally, degenerative alterations of the exocrine pancreas were prominent in groups 1 and 3. Lesions in group 3 were more pronounced than in group 1. In group 3, the skin showed an atrophic dermatosis, while in group 2 a crusty dermatitis caused by Candida spp. was observed. This study shows that liver, pancreas and skin are mainly affected by a long term deficiency of copper and the findings are complicated by molybdenum application while chromium deficiency produced no histomorphological effects in our study.

  15. Vitamin K deficiency bleeding in cholestatic infants with alpha-1-antitrypsin deficiency.

    NARCIS (Netherlands)

    Hasselt, P.M. van; Kok, K.F.; Vorselaars, A.D.; Vlerken, L. van; Nieuwenhuys, E.; Koning, T.J. de; Vries, R.A. de; Houwen, R.H.J.

    2009-01-01

    OBJECTIVE: Exclusively breastfed infants with unrecognised cholestatic jaundice are at high risk of a vitamin K deficiency (VKD) bleeding. It is presently unknown whether (the size of) this risk depends on the degree of cholestasis. Since alpha-1-antitrypsin deficiency (A1AD) induces a variable degr

  16. Vitamin K deficiency bleeding in cholestatic infants with alpha-1-antitrypsin deficiency

    NARCIS (Netherlands)

    van Hasselt, P. M.; Kok, K.; Vorselaars, A. D. M.; van Vlerken, L.; Nieuwenhuys, E.; de Koning, T. J.; de Vries, Rindert; Houwen, R. H. J.

    2009-01-01

    Objective: Exclusively breastfed infants with unrecognised cholestatic jaundice are at high risk of a vitamin K deficiency (VKD) bleeding. It is presently unknown whether (the size of) this risk depends on the degree of cholestasis. Since alpha-l-antitrypsin deficiency (A1AD) induces a variable degr

  17. Zinc Deficiency in Humans and its Amelioration

    Directory of Open Access Journals (Sweden)

    Yashbir Singh Shivay

    2015-01-01

    Full Text Available Zinc (Zn deficiency in humans has recently received considerable attention. Global mortality in children under 5 years of age in 2004 due to Zn deficiency was estimated at 4,53,207 as against 6,66,771 for vitamin A deficiency; 20,854 for iron deficiency and 3,619 for iodine deficiency. In humans 2800-3000 proteins contain Zn prosthetic group and Zn is an integral component of zinc finger prints that regulate DNA transcription. Zinc is a Type-2 nutrient, which means that its concentration in blood does not decrease in proportion of the Zn deficiency. Adverse effects of Zn deficiency vary with age: low weight gain, diarrhoea, aneroxia and neurobehavioral disturbances are observed in infants, while skin changes and dwarfism are frequent in toddlers and adolescents. Common manifestations of Zn deficiency among elderly include hypogeusia, chronic non-healing ulcers and recurrent infections.Ameliorative measures of Zn deficiency in humans can be classified in two groups, namely, nutraceutical and biofortification of food grains. Nutraceutical interventions include pharmaceutical supplements, dietary supplements and dietary diversification, while biofortification of food grains can be achieved by genetic modification (GM of crops or by agronomic techniques that include soil or/and foliar fertilization of crops.The major disadvantage of nutraceutical approaches is that the major beneficiaries are urban people and the poor rural masses that need adequate Zn nutrition most are left out. Genetic biofortification of food grains requires large amounts of funds and a fairly long-period of time. Further, a large number of countries have not yet accepted genetically modified (GM foods. On the other hand agronomic biofortification of food grains yields immediate effects and rural and urban people are equally benefitted. Our studies have shown that Zn concentration in cereals (rice, wheat etc and pulses can be considerably increased by soil or/and foliar

  18. Vitamin D Deficiency Among Professional Basketball Players.

    Science.gov (United States)

    Fishman, Matthew P; Lombardo, Stephen J; Kharrazi, F Daniel

    2016-07-01

    Vitamin D plays an important role in several systems of the human body. Various studies have linked vitamin D deficiency to stress and insufficiency fractures, muscle recovery and function, and athletic performance. The prevalence of vitamin D deficiency in the elite athletic population has not been extensively studied, and very few reports exist among professional athletes. There is a high prevalence of vitamin D deficiency or insufficiency among players attending the National Basketball Association (NBA) Combine. Cross-sectional study; Level of evidence, 3. This is a retrospective review of data previously collected as part of the routine medical evaluation of players in the NBA Combines from 2009 through 2013. Player parameters evaluated were height, weight, body mass index (BMI), and vitamin D level. Statistical analysis using t tests and analysis of variance was used to detect any correlation between the player parameters and vitamin D level. Vitamin D levels were categorized as deficient (32 ng/mL). After institutional review board approval was submitted to the NBA, the NBA released deidentified data on 279 players who participated in the combines from 2009 through 2013. There were 90 players (32.3%) who were deficient, 131 players (47.0%) who were insufficient, and 58 players (20.8%) who were sufficient. A total of 221 players (79.3%) were either vitamin D deficient or insufficient. Among all players included, the average vitamin D level was 25.6 ± 10.2 ng/mL. Among the players who were deficient, insufficient, and sufficient, the average vitamin D levels were 16.1 ± 2.1 ng/mL, 25.0 ± 3.4 ng/mL, and 41.6 ± 8.6 ng/mL, respectively. Player height and weight were significantly increased in vitamin D-sufficient players compared with players who were not sufficient (P = .0008 and .009, respectively). Player age and BMI did not significantly differ depending on vitamin D status (P = .15 and .77, respectively). There is a high prevalence of vitamin D deficiency

  19. [Control of iron deficiency in developing countries].

    Science.gov (United States)

    Berger, Jacques; Dillon, Jean-Claude

    2002-01-01

    Iron deficiency is the most prevalent nutritional disorder worldwide, especially in developing countries. It occurs when iron absorption cannot compensate iron requirements and losses. Requirements are especially high in pregnant women, infants, young children and adolescents who run a higher risk of being iron-deficient. In developing countries, the main cause of iron deficiency is the low iron bioavailability of the diet. The consequences of iron deficiency are many and serious, affecting not only individuals' health but also the development of societies and countries. The prevention and the control of iron deficiency and anemia in all groups of a population with different iron requirements imply to coordinate different interventions. Iron fortification of staple foods or condiments directed to the whole population is a sustainable and low cost-effective approach. However, at some periods of life, especially during pregnancy and in children from the age of 6 months, iron requirements are high. For pregnant women, the current approach favours the daily iron-folate supplementation during pregnancy but the results in terms of public health are disappointing. The preventive weekly iron-folate supplementation of women during their reproductive life, whose efficacy is recognized, offers a promising alternative; its impact in terms of public health is under current evaluation. For infants and young children, iron fortification of complementary food is effective but this food is generally imported and economically inaccessible to populations with limited resources. The production, by small private units from local products, of complementary foods of low viscosity, good nutritional quality, fortified with vitamins and minerals, and of low cost is at hand in several countries. When complementary foods are not available, the preventive iron supplementation from 6 to 18 months of age has to be advised. This approach should be strengthened by the advantages of the weekly

  20. Vitamin D Deficiency in Medical Inpatients: A Retrospective Study of Implications of Untreated Versus Treated Deficiency

    Science.gov (United States)

    Zaidi, Syed Asher Hussain; Singh, Gurjit; Owojori, Olukolade; Kela, Ram; Spoors, Shirley; Abbas, Mohamed; Barton, Florence; Rogers, Caroline

    2016-01-01

    Vitamin D deficiency and insufficiency may further increase fracture risk in patients with decreased bone mineral density. A cross-sectional study on serum vitamin D concentrations in medical inpatients was conducted at Bassetlaw District General Hospital between April 2014 and January 2015 (10 months), and the relationship of serum vitamin D concentrations with calcium and alkaline phosphatase was evaluated. 25-Hydroxyvitamin D immunoassays were used and analyzed in the local laboratory. The total number of patients analyzed was 200, age range 18–99 years, with mean age of 76 years. The most common presentation was found to be fall/collapse. The following cutoff points for serum vitamin D were used: levels ≤30 nmol/L for severe deficiency, >30–50 nmol/L for moderate deficiency, >50–75 nmol/L for mild deficiency, and anything above 75 nmol/L as normal. Of the 209 participants examined, 78 (37.3%) participants had mild vitamin D deficiency, 54 (25.8%) participants had moderate vitamin D deficiency, 68 (32.5%) participants had severe vitamin D deficiency, and 9 (4.3%) participants with low vitamin D levels died during their admission. Of the 122 moderate/severe patients, 70 (57.4%) patients had their vitamin D deficiency treated, according to local Trust guidelines. The study found no relationship between serum calcium levels and vitamin D deficiency, whereas patients’ alkaline phosphatase levels were found to be higher with increased severity of vitamin D deficiency. The study examined the implications of untreated severe/moderate vitamin D deficiency compared to treated deficiency, in terms of the frequency of readmission with similar complaints. It was found that the rate of readmission within one year in patients who were not treated was 57%, compared to 48% in patients whose vitamin D deficiency was treated. Presenting after falls was a recurring theme. It was concluded that even if moderate vitamin D deficiency can be asymptomatic, it is important to

  1. Thyroid disorders in mild iodine deficiency.

    Science.gov (United States)

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

    2000-11-01

    Comparative epidemiologic studies in areas with low and high iodine intake and controlled studies of iodine supplementation have demonstrated that the major consequence of mild-to-moderate iodine deficiency for the health of the population is an extraordinarily high occurrence of hyperthyroidism in elderly subjects, especially women, with risk of cardiac arrhythmias, osteoporosis, and muscle wasting. The hyperthyroidism is caused by autonomous nodular growth and function of the thyroid gland and it is accompanied by a high frequency of goiter. Pregnant women and small children are not immediately endangered but the consequences of severe iodine deficiency for brain development are grave and a considerable safety margin is advisable. Moreover, a shift toward less malignant types of thyroid cancer and a lower radiation dose to the thyroid in case of nuclear fallout support that mild-to-moderate iodine deficiency should be corrected. However, there is evidence that a high iodine intake may be associated with more autoimmune hypothyroidism, and that Graves' disease may manifest at a younger age and be more difficult to treat. Hence, the iodine intake should be brought to a level at which iodine deficiency disorders are avoided but not higher. Iodine supplementation programs should aim at relatively uniform iodine intake, avoiding deficient or excessive iodine intake in subpopulations. To adopt such a strategy, surveillance programs are needed.

  2. Clinical implications of vitamin D deficiency

    Directory of Open Access Journals (Sweden)

    Beata Matyjaszek-Matuszek

    2015-06-01

    Full Text Available Vitamin D deficiency is a common medical problem worldwide and its prevalence rises along with latitude, obesity, sedentary lifestyle, limited sunlight exposure and aging. A great body of evidence has shown that patients with vitamin D deficiency have increased cardiovascular risks and total mortality. Conversely, the presence of comorbidities progressive with age such as abdominal obesity, insulin resistance, type 2 diabetes and hypertension places the patients at an increased risk of vitamin D deficiency. The multidirectional effect of vitamin D deficiency is present in different phases of the aging process. Based on the literature review, the risk factors for vitamin D insufficiency most often found in post-menopausal women include limited sun exposure and time spent outdoors, inadequate dietary vitamin D intake, winter season and increased age. Vitamin D supplementation in this group might offer prevention of falls and fractures and may be beneficial for cardiovascular health, what may be especially important in osteoporotic and elderly populations. Prevention and treatment processes involve education regarding sunlight exposure and pharmacological cholecalciferol supplementation according to the recommendations for Central Europe. This manuscript reviews the role of vitamin D and its deficiency and considers their clinical implications, with particular regard to peri- and postmenopausal women.

  3. Caspase 12 in calnexin-deficient cells.

    Science.gov (United States)

    Groenendyk, Jody; Zuppini, Anna; Shore, Gordon; Opas, Michal; Bleackley, R Chris; Michalak, Marek

    2006-11-07

    We investigated a role for calnexin, caspase 12, and Bap31 in endoplasmic reticulum stress-induced apoptosis in calnexin-deficient mouse embryonic fibroblasts and a calnexin-deficient human T cell line (NKR). We showed that calnexin-deficient mouse embryonic fibroblasts are relatively resistant to endoplasmic reticulum stress-induced apoptosis. Western blot analysis demonstrated that both wild-type and calnexin-deficient cells contained a caspase 12 protein. Caspase 12 expression was slightly inhibited in calnexin-deficient cells, and the protein carried out specific cleavage in the presence of thapsigargin. Immunoprecipitation experiments revealed that in the endoplasmic reticulum, caspase 12 forms complexes with Bap31 and calnexin. Treatment of wild-type cells with thapsigargin induced apoptosis and cleavage of Bap31. However, in the absence of calnexin, there was no significant cleavage of Bap31. There was also a negligible processing of caspase 8 in these cells. This work indicates that calnexin may play a role in modulating the sensitivity of a cell to apoptosis induced by endoplasmic reticulum stress, in conjunction with caspase 12 and Bap31.

  4. Biochemical Assessment of Coenzyme Q10 Deficiency

    Directory of Open Access Journals (Sweden)

    Juan Carlos Rodríguez-Aguilera

    2017-03-01

    Full Text Available Coenzyme Q10 (CoQ10 deficiency syndrome includes clinically heterogeneous mitochondrial diseases that show a variety of severe and debilitating symptoms. A multiprotein complex encoded by nuclear genes carries out CoQ10 biosynthesis. Mutations in any of these genes are responsible for the primary CoQ10 deficiency, but there are also different conditions that induce secondary CoQ10 deficiency including mitochondrial DNA (mtDNA depletion and mutations in genes involved in the fatty acid β-oxidation pathway. The diagnosis of CoQ10 deficiencies is determined by the decrease of its content in skeletal muscle and/or dermal skin fibroblasts. Dietary CoQ10 supplementation is the only available treatment for these deficiencies that require a rapid and distinct diagnosis. Here we review methods for determining CoQ10 content by HPLC separation and identification using alternative approaches including electrochemical detection and mass spectrometry. Also, we review procedures to determine the CoQ10 biosynthesis rate using labeled precursors.

  5. Overview: recognizing the problem of magnesium deficiency

    Energy Technology Data Exchange (ETDEWEB)

    Seelig, M.S.

    1988-01-01

    The magnesium content of the usual American diet is less than the recommended dietary allowance. Excesses of some macro- and micro-nutrients interact with Mg, increasing its requirements. Marginal deficiency of Mg is not associated with hypomagnesemia, is not characterized by typical manifestations, as is thus difficult to diagnose. Serum or plasma Mg levels are held within narrow limits unless tissue levels are very low, or renal function is poor. Vulnerability to Mg deficiency increases during growth and development, pregnancy, when under physical or psychological stress, and during illness or its treatment that interferes with absorption or causes loss of Mg. Evidence of biochemical changes of early Mg deficiency is rarely sought, although the roles of Mg in many enzyme systems are recognized. The effects of Mg deficiency on metabolism, even in disorders caused by vitamin dependencies in which Mg is a co-factor, are largely unexplored. Deficiency of Mg is diagnosed confidently when the laboratory reports hypomagnesemia in patients with convulsions or arrhythmias. Without these signs, Mg levels are not often ordered, even in the presence of neuromuscular irritability such as respond to Mg repletion. Because Mg supplementation or Mg-sparing drugs protect against premature or ectopic heart beats and sudden death, to which diuretic-treated hypertensive patients are at risk, it is increasingly being advised that their Mg status be determined.

  6. The epidemiology of global micronutrient deficiencies.

    Science.gov (United States)

    Bailey, Regan L; West, Keith P; Black, Robert E

    2015-01-01

    Micronutrients are essential to sustain life and for optimal physiological function. Widespread global micronutrient deficiencies (MNDs) exist, with pregnant women and their children under 5 years at the highest risk. Iron, iodine, folate, vitamin A, and zinc deficiencies are the most widespread MNDs, and all these MNDs are common contributors to poor growth, intellectual impairments, perinatal complications, and increased risk of morbidity and mortality. Iron deficiency is the most common MND worldwide and leads to microcytic anemia, decreased capacity for work, as well as impaired immune and endocrine function. Iodine deficiency disorder is also widespread and results in goiter, mental retardation, or reduced cognitive function. Adequate zinc is necessary for optimal immune function, and deficiency is associated with an increased incidence of diarrhea and acute respiratory infections, major causes of death in those diversification. It is widely accepted that intervention in the first 1,000 days is critical to break the cycle of malnutrition; however, a coordinated, sustainable commitment to scaling up nutrition at the global level is still needed. Understanding the epidemiology of MNDs is critical to understand what intervention strategies will work best under different conditions.

  7. Sneddon syndrome associated with Protein S deficiency.

    Science.gov (United States)

    Sayin, Refah; Bilgili, Serap Gunes; Karadag, Ayse Serap; Tombul, Temel

    2012-01-01

    Sneddon syndrome (SS) is rare, arterio-occlusive disorder characterized by generalized livedo racemosa of the skin and various central nervous symptoms due to occlusion of medium-sized arteries of unknown. Seizure, cognitive impairment, hypertension, and history of repetitive miscarriages are the other symptoms seen in this disease. Livedo racemosa involves persisting irreversible skin lesions red or blue in color with irregular margins. Usually, SS occurs in women of childbearing age. Protein S deficiency is an inherited or acquired disorder associated with an increased risk of thrombosis. We present a 33-year-old woman with SS with diffuse livedo racemosa, recurrent cerebrovascular diseases, migraine-type headache, sinus vein thrombosis, and protein S deficiency. Protein S deficiency and with Sneddon syndrome rarely encountered in the literature.

  8. MRI findings of complete growth hormone deficiency

    Energy Technology Data Exchange (ETDEWEB)

    Ichiba, Yozo [National Hospital of Okayama (Japan)

    1995-10-01

    Magnetic resonance (MR) imaging was performed on the pituitary gland of 20 children (age range, 2-11 years) with short stature due to growth hormone deficiency. Sixteen patients with multiple pituitary hormone deficiency showed disappearance of the pituitary stalk, disappearance of high signal area of the posterior pituitary, presence of ectopic pituitary, and decreased volume of the anterior pituitary. Many of them had a history of perinatal abnormalities such as asphyxia at delivery, breech delivery, and bradytocia. On the contrary, patients with isolated growth hormone deficiency presented no abnormal findings on MR images, and had no history of perinatal abnormalities. The findings of pituitary stalk separation syndrome suggested the presence of multiple hypopituitarism. (S.Y.).

  9. Paroxysmal Nonepileptic Events in Glut1 Deficiency.

    Science.gov (United States)

    Klepper, Joerg; Leiendecker, Baerbel; Eltze, Christin; Heussinger, Nicole

    2016-01-01

    View Supplementary Video Movement disorders are a major feature of Glut1 deficiency. As recently identified in adults with paroxysmal exercise-induced dystonia, similar events were reported in pediatric Glut1 deficiency. In a case series, parent videos of regular motor state and paroxysmal events were requested from children with Glut1 deficiency on clinical follow-up. A questionnaire was sent out to 60 families. Videos of nonparoxysmal/paroxysmal states in 3 children illustrated the ataxic-dystonic, choreatiform, and dyskinetic-dystonic nature of paroxysmal events. Fifty-six evaluated questionnaires confirmed this observation in 73% of patients. Events appeared to increase with age, were triggered by low ketosis, sleep deprivation, and physical exercise, and unrelated to sex, hypoglycorrhachia, SLC2A1 mutations, or type of ketogenic diet. We conclude that paroxysmal events are a major clinical feature in Glut1 deficieny, linking the pediatric disease to adult Glut1D-associated exercise-induced paroxysmal dyskinesias.

  10. Ornithine Transcarbamylase Deficiency in Iranian Children

    Directory of Open Access Journals (Sweden)

    HR Joshaghani

    2003-08-01

    Full Text Available Ammonia is a toxic material for mammalians. It is detoxificated and converted to urea in the urea cycle in liver. Each defect in the urea cycle cause increase in blood ammonia level. Ornithine transcarbamylase enzyme (OTC is the second enzyme in the urea cycle that exists in mitochondria. OTC deficiency is the most common hereditary disorder in the urea cycle. In this study, 45 hyper ammonia patients were selected (2-13 years old and assayed for serum OTC, serum aspartate aminotransferase (AST, serum alanine aminotransferase (ALT. Four patients (n=45, 8.9% suffered from OTC deficiency. One patient was male (n=29, 3.4% and the others were female (n=16, 18.8%. About half of children (53.3 with hyper ammonia have liver disease. Further studies on OTC deficiency and OTC gene mutations in Iran are recommended.

  11. Multispectral Analysis of Color Vision Deficiency Tests

    Directory of Open Access Journals (Sweden)

    Sergejs FOMINS

    2011-03-01

    Full Text Available Color deficiency tests are usually produced by means of polygraphy technologies and help to diagnose the type and severity of the color deficiencies. Due to different factors, as lighting conditions or age of the test, standard characteristics of these tests fail, thus not allowing diagnosing unambiguously the degree of different color deficiency. Multispectral camera was used to acquire the spectral images of the Ishihara and Rabkin pseudoisochromatic plates in the visible spectrum. Spectral data was converted to cone signals, and successive mathematics applied to provide a simple simulation of the test performance. Colorimetric data of the each pixel of the test image can be calculated and distribution of color coordinates is presented.http://dx.doi.org/10.5755/j01.ms.17.1.259

  12. Model of how plants sense zinc deficiency

    DEFF Research Database (Denmark)

    Assuncao, Ana G.L.; Persson, Daniel Olof; Husted, Søren;

    2013-01-01

    to develop plant-based solutions addressing nutrient-use-efficiency and adaptation to nutrient-limited or -toxic soils. Recently two transcription factors of the bZIP family (basic-region leucine zipper) have been identified in Arabidopsis and shown to be pivotal in the adaptation response to zinc deficiency....... They represent not only the first regulators of zinc homeostasis identified in plants, but also a very promising starting-point that can provide new insights into the molecular basis of how plants sense and adapt to the stress of zinc deficiency. Considering the available information thus far we propose...... in this review a putative model of how plants sense zinc deficiency....

  13. [Testosterone deficiency, metabolic syndrome and diabetes mellitus].

    Science.gov (United States)

    Fernández-Miró, Mercè; Chillarón, Juan J; Pedro-Botet, Juan

    2016-01-15

    Testosterone deficiency in adult age is associated with a decrease in libido, energy, hematocrit, muscle mass and bone mineral density, as well as with depression. More recently, testosterone deficiency has also been associated with various components of the metabolic syndrome, which in turn is associated with a five-fold increase in the risk of cardiovascular disease. Low testosterone levels are associated with increased insulin resistance, increase in fat mass, low HDL cholesterol, higher triglyceride levels and hypertension. Testosterone replacement therapy in patients with testosterone deficiency and type 2 diabetes mellitus and/or metabolic syndrome has shown reductions in insulin resistance, total cholesterol, LDL cholesterol and triglycerides and improvement in glycemic control and anthropometric parameters. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

  14. Sneddon syndrome associated with Protein S deficiency

    Directory of Open Access Journals (Sweden)

    Refah Sayin

    2012-01-01

    Full Text Available Sneddon syndrome (SS is rare, arterio-occlusive disorder characterized by generalized livedo racemosa of the skin and various central nervous symptoms due to occlusion of medium-sized arteries of unknown. Seizure, cognitive impairment, hypertension, and history of repetitive miscarriages are the other symptoms seen in this disease. Livedo racemosa involves persisting irreversible skin lesions red or blue in color with irregular margins. Usually, SS occurs in women of childbearing age. Protein S deficiency is an inherited or acquired disorder associated with an increased risk of thrombosis. We present a 33-year-old woman with SS with diffuse livedo racemosa, recurrent cerebrovascular diseases, migraine-type headache, sinus vein thrombosis, and protein S deficiency. Protein S deficiency and with Sneddon syndrome rarely encountered in the literature.

  15. Experimental models of melatonin-deficient hypertension.

    Science.gov (United States)

    Simko, Fedor; Reiter, Russel J; Pechanova, Olga; Paulis, Ludovit

    2013-01-01

    Melatonin secreted by the pineal gland plays an important role in the regulation of blood pressure (BP) and its administration reduces hypertension both in animals and humans. There are two experimental models of melatonin-deficient hypertension: one induced by pinealectomy and another by continuous 24 hour exposure to light. Both models cause melatonin deficiency and prevent darkness-mediated nocturnal melatonin secretion and are associated with increased BP and myocardial, vascular and renal dysfunction. These models also lead to neurohumoral activation of the renin-angiotensin system, sympathetic nervous system, adrenocorticotrophin-glucocorticoid axis and cause insulin resistance. Together, these alterations contribute to rise in blood pressure by vasoconstrictive or circulatory fluid volume overload. The light induced hypertension model mimics the melatonin deficiency in patients with insufficient nocturnal BP decline, in those who have night shift or who are exposed to environmental light pollution. For this reason, this model is useful in development of anti-hypertensive drugs.

  16. 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.

  17. Cited1 deficiency suppresses intestinal tumorigenesis.

    Directory of Open Access Journals (Sweden)

    Valérie Méniel

    Full Text Available Conditional deletion of Apc in the murine intestine alters crypt-villus architecture and function. This process is accompanied by multiple changes in gene expression, including upregulation of Cited1, whose role in colorectal carcinogenesis is unknown. Here we explore the relevance of Cited1 to intestinal tumorigenesis. We crossed Cited1 null mice with Apc(Min/+ and AhCre(+Apc(fl/fl mice and determined the impact of Cited1 deficiency on tumour growth/initiation including tumour multiplicity, cell proliferation, apoptosis and the transcriptome. We show that Cited1 is up-regulated in both human and murine tumours, and that constitutive deficiency of Cited1 increases survival in Apc(Min/+ mice from 230.5 to 515 days. However, paradoxically, Cited1 deficiency accentuated nearly all aspects of the immediate phenotype 4 days after conditional deletion of Apc, including an increase in cell death and enhanced perturbation of differentiation, including of the stem cell compartment. Transcriptome analysis revealed multiple pathway changes, including p53, PI3K and Wnt. The activation of Wnt through Cited1 deficiency correlated with increased transcription of β-catenin and increased levels of dephosphorylated β-catenin. Hence, immediately following deletion of Apc, Cited1 normally restrains the Wnt pathway at the level of β-catenin. Thus deficiency of Cited1 leads to hyper-activation of Wnt signaling and an exaggerated Wnt phenotype including elevated cell death. Cited1 deficiency decreases intestinal tumourigenesis in Apc(Min/+ mice and impacts upon a number of oncogenic signaling pathways, including Wnt. This restraint imposed by Cited1 is consistent with a requirement for Cited1 to constrain Wnt activity to a level commensurate with optimal adenoma formation and maintenance, and provides one mechanism for tumour repression in the absence of Cited1.

  18. Circadian behaviour in neuroglobin deficient mice

    DEFF Research Database (Denmark)

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

    2012-01-01

    Neuroglobin (Ngb), a neuron-specific oxygen-binding globin with an unknown function, has been proposed to play a key role in neuronal survival. We have previously shown Ngb to be highly expressed in the rat suprachiasmatic nucleus (SCN). The present study addresses the effect of Ngb deficiency......-induced increase in Per1, but not Fos, gene expression was observed in Ngb-deficient mice. Ngb expressing neurons which co-stored Gastrin Releasing Peptide (GRP) and were innervated from the eye and the geniculo-hypothalamic tract expressed FOS after light stimulation. No PER1 expression was observed in Ngb...

  19. Zinc and biotin deficiencies after pancreaticoduodenectomy.

    Science.gov (United States)

    Yazbeck, N; Muwakkit, S; Abboud, M; Saab, R

    2010-01-01

    We report zinc and biotin deficiencies after pancreaticoduodenectomy in a 16 year old female presenting clinically with marked alopecia, total body hair loss, dry skin with scales, and maculopathy with significant vision loss. These micronutrient deficiencies likely occurred due to resection of the duodenum and proximal jejunum, sites of primary absorption of several micronutrients and their protein carriers, including zinc and biotin. Early diagnosis is essential to prevent irreversible sequelae. Adequate supplementation of zinc and biotin as well as dietary advice is needed for clinical improvement.

  20. Vitamin C deficiency in an anticoagulated patient.

    Science.gov (United States)

    Yousef, George M; Goebel, Lynne J

    2013-06-01

    A 64-year-old woman presented with a hemorrhagic perifollicular rash on her legs while taking warfarin. After biopsy, vitamin C deficiency was suggested as the diagnosis, which ascorbic acid assays later confirmed. Clinical resolution of the rash followed supplementation with vitamin C. Patients on a vitamin K limited diet may also be limiting their intake of vitamin C. Physicians should be aware of this possible correlation, and consider checking vitamin C levels in patients with a perifollicular hemorrhagic rash or other signs of vitamin C deficiency while on warfarin.

  1. Rickets-vitamin D deficiency and dependency

    Directory of Open Access Journals (Sweden)

    Manisha Sahay

    2012-01-01

    Full Text Available Rickets is an important problem even in countries with adequate sun exposure. The causes of rickets/osteomalacia are varied and include nutritional deficiency, especially poor dietary intake of vitamin D and calcium. Non-nutritional causes include hypophosphatemic rickets primarily due to renal phosphate losses and rickets due to renal tubular acidosis. In addition, some varieties are due to inherited defects in vitamin D metabolism and are called vitamin D dependent rickets. This chapter highlights rickets/osteomalacia related to vitamin D deficiency or to inherited defects in vitamin D metabolism. Hypophosphatemic rickets and rickets due to renal tubular acidosis are discussed in other sections of the journal.

  2. The molecular basis of aminoacylase 1 deficiency

    DEFF Research Database (Denmark)

    Sommer, Anke; Christensen, Ernst; Schwenger, Susanne

    2011-01-01

    deficiency have not been characterized so far. This has prompted us to approach expression studies of all mutations known to occur in aminoacylase 1 deficient individuals in a human cell line (HEK293), thus providing the authentic human machinery for posttranslational modifications. Mutations were inserted...... by their intramolecular localization and molecular characteristics. In contrast to aminoacylase 1 variants which showed no detectable aminoacylase 1 activity, aminoacylase 1 proteins with the mutations p.Arg378Trp, p.Arg378Gln and p.Arg393His were also detected in Western blot analysis. Investigations of the molecular...

  3. Phenylalanine hydroxylase deficiency: diagnosis and management guideline.

    Science.gov (United States)

    Vockley, Jerry; Andersson, Hans C; Antshel, Kevin M; Braverman, Nancy E; Burton, Barbara K; Frazier, Dianne M; Mitchell, John; Smith, Wendy E; Thompson, Barry H; Berry, Susan A

    2014-02-01

    Phenylalanine hydroxylase deficiency, traditionally known as phenylketonuria, results in the accumulation of phenylalanine in the blood of affected individuals and was the first inborn error of metabolism to be identified through population screening. Early identification and treatment prevent the most dramatic clinical sequelae of the disorder, but new neurodevelopmental and psychological problems have emerged in individuals treated from birth. The additional unanticipated recognition of a toxic effect of elevated maternal phenylalanine on fetal development has added to a general call in the field for treatment for life. Two major conferences sponsored by the National Institutes of Health held >10 years apart reviewed the state of knowledge in the field of phenylalanine hydroxylase deficiency, but there are no generally accepted recommendations for therapy. The purpose of this guideline is to review the strength of the medical literature relative to the treatment of phenylalanine hydroxylase deficiency and to develop recommendations for diagnosis and therapy of this disorder. Evidence review from the original National Institutes of Health consensus conference and a recent update by the Agency for Healthcare Research and Quality was used to address key questions in the diagnosis and treatment of phenylalanine hydroxylase deficiency by a working group established by the American College of Medical Genetics and Genomics. The group met by phone and in person over the course of a year to review these reports, develop recommendations, and identify key gaps in our knowledge of this disorder. Above all, treatment of phenylalanine hydroxylase deficiency must be life long, with a goal of maintaining blood phenylalanine in the range of 120-360 µmol/l. Treatment has predominantly been dietary manipulation, and use of low protein and phenylalanine medical foods is likely to remain a major component of therapy for the immediate future. Pharmacotherapy for phenylalanine

  4. Sleep Transitions in Hypocretin-Deficient Narcolepsy

    DEFF Research Database (Denmark)

    Sorensen, Gertrud Laura; Knudsen, Stine; Jennum, Poul

    2013-01-01

    Narcolepsy is characterized by instability of sleep-wake, tonus, and rapid eye movement (REM) sleep regulation. It is associated with severe hypothalamic hypocretin deficiency, especially in patients with cataplexy (loss of tonus). As the hypocretin neurons coordinate and stabilize the brain......'s sleep-wake pattern, tonus, and REM flip-flop neuronal centers in animal models, we set out to determine whether hypocretin deficiency and/or cataplexy predicts the unstable sleep-wake and REM sleep pattern of the human phenotype....

  5. Vitamin A deficiency in Crohn's disease.

    OpenAIRE

    Main, A N; Mills, P. R.; Russell, R I; Bronte-Stewart, J; Nelson, L. M.; McLelland, A; Shenkin, A

    1983-01-01

    Fifty two patients with Crohn's disease (31 outpatients and 21 inpatients) were investigated for evidence of vitamin A deficiency. Eleven (21%) had low plasma retinol concentrations (less than 1.2 mumol/l (34.3 micrograms %)). Five of these were outpatients and plasma retinol was only slightly reduced (greater than 1.0 mumol/l (28.6%)). All outpatients weighed 80% or more of ideal, and were considered at low risk of developing vitamin A deficiency. In contrast, of the six inpatients with low ...

  6. High Prevalence of Vitamin B12 Deficiency and No Folate Deficiency in Young Children in Nepal.

    Science.gov (United States)

    Ng'eno, Bernadette N; Perrine, Cria G; Whitehead, Ralph D; Subedi, Giri Raj; Mebrahtu, Saba; Dahal, Pradiumna; Jefferds, Maria Elena D

    2017-01-17

    Many children in low- and middle-income countries may have inadequate intake of vitamin B12 and folate; data confirming these inadequacies are limited. We used biochemical, demographic, behavioral and anthropometric data to describe the folate and vitamin B12 concentrations among six- to 23-month-old Nepalese children. Vitamin B12 (serum B12 B12 deficiency. The vitamin B12 geometric mean was 186 pmol/L; 30.2% of children were deficient. The mean RBC folate concentration was 13,612 nmol/L; there was no deficiency. Factors associated with vitamin B12 deficiency included: (a) age six to 11 months (adjusted odds ratio (aOR) 1.51; 95% confidence interval (CI): 1.18, 1.92) or 12-17 months (aOR 1.38; 95% CI: 1.10, 1.72) compared to 18-23 months; (b) being stunted (aOR 1.24; 95% CI: 1.03, 1.50) compared to not being stunted; (c) and not eating animal-source foods (aOR 1.85; 95% CI: 1.42, 2.41) compared to eating animal-source foods the previous day. There was a high prevalence of vitamin B12 deficiency, but no folate deficiency. Improving early feeding practices, including the consumption of rich sources of vitamin B12, such as animal-source foods and fortified foods, may help decrease deficiency.

  7. Risk factors associated with anemia, iron deficiency and iron deficiency anemia in rural Nepali pregnant women.

    Science.gov (United States)

    Makhoul, Zeina; Taren, Douglas; Duncan, Burris; Pandey, Pooja; Thomson, Cynthia; Winzerling, Joy; Muramoto, Myra; Shrestha, Ram

    2012-05-01

    We conducted a cross sectional study to investigate risk factors associated with severe anemia [hemoglobin (Hb) iron status among Nepali pregnant women. Socio-demographic, anthropometric, health and dietary data were collected from 3,531 women living in the southeastern plains of Nepal. Stool samples were analyzed for intestinal helminthes. Dark adaptation was assessed using the Night Vision Threshold Test (NVTT). Hb levels were measured in all subjects to detect anemia and the soluble transferrin receptor (sTfR) was measured among a subsample of 479 women. The iron status categories were: 1) normal (Hb> or = 11.0 g/dl and sTfR anemia without iron deficiency (Hbiron deficiency without anemia (Hb > or = 11.0 g/dl and sTfR>8.5 mg/l); and 4) iron deficiency anemia (IDA): (Hb8.5 mg/l). Factors associated with severe anemia and poor iron status were determined using logistic regression. Hookworm infection increased the risk for developing severe anemia [adjusted odds ratio (AOR): 4.26; 95% CI 1.67-10.89; piron deficiency with and without anemia. Intake of iron supplements as tablets and/or tonic was protective against severe anemia, anemia without iron deficiency and IDA. Dietary heme iron was significantly associated with iron deficiency without anemia (RRR: 0.1; 95% CI 0.02-0.47; panemia and associated nutrient deficiencies.

  8. [A neonate with anaemia of prematurity: zinc protoporphyrin identifies iron deficiency anaemia without iron deficiency].

    Science.gov (United States)

    van der Feen, Diederik E; van Hillegersberg, Jacqueline L A M; Schippers, Johannes A

    2015-01-01

    Anaemia is a common problem in premature infants and is generally easy to treat with iron supplementation. If the anaemia persists despite appropriate correction of deficiencies, more extensive evaluation is required. We describe a case of a premature male infant with a production-deficient anaemia without metabolic deficiencies, eventually identified as anaemia of prematurity. This type of anaemia is commonly diagnosed but its highly variable and complex aetiology and phenotype are often poorly understood. A probable explanation for the anaemia of prematurity in this case was a transient iron incorporation defect, identifiable by high levels of zinc protoporphyrin.

  9. Circadian behaviour in neuroglobin deficient mice.

    Directory of Open Access Journals (Sweden)

    Christian A Hundahl

    Full Text Available Neuroglobin (Ngb, a neuron-specific oxygen-binding globin with an unknown function, has been proposed to play a key role in neuronal survival. We have previously shown Ngb to be highly expressed in the rat suprachiasmatic nucleus (SCN. The present study addresses the effect of Ngb deficiency on circadian behavior. Ngb-deficient and wild-type (wt mice were placed in running wheels and their activity rhythms, endogenous period and response to light stimuli were investigated. The effect of Ngb deficiency on the expression of Period1 (Per1 and the immediate early gene Fos was determined after light stimulation at night and the neurochemical phenotype of Ngb expressing neurons in wt mice was characterized. Loss of Ngb function had no effect on overall circadian entrainment, but resulted in a significantly larger phase delay of circadian rhythm upon light stimulation at early night. A light-induced increase in Per1, but not Fos, gene expression was observed in Ngb-deficient mice. Ngb expressing neurons which co-stored Gastrin Releasing Peptide (GRP and were innervated from the eye and the geniculo-hypothalamic tract expressed FOS after light stimulation. No PER1 expression was observed in Ngb-positive neurons. The present study demonstrates for the first time that the genetic elimination of Ngb does not affect core clock function but evokes an increased behavioural response to light concomitant with increased Per1 gene expression in the SCN at early night.

  10. Circadian behaviour in neuroglobin deficient mice.

    Science.gov (United States)

    Hundahl, Christian A; Fahrenkrug, Jan; Hay-Schmidt, Anders; Georg, Birgitte; Faltoft, Birgitte; Hannibal, Jens

    2012-01-01

    Neuroglobin (Ngb), a neuron-specific oxygen-binding globin with an unknown function, has been proposed to play a key role in neuronal survival. We have previously shown Ngb to be highly expressed in the rat suprachiasmatic nucleus (SCN). The present study addresses the effect of Ngb deficiency on circadian behavior. Ngb-deficient and wild-type (wt) mice were placed in running wheels and their activity rhythms, endogenous period and response to light stimuli were investigated. The effect of Ngb deficiency on the expression of Period1 (Per1) and the immediate early gene Fos was determined after light stimulation at night and the neurochemical phenotype of Ngb expressing neurons in wt mice was characterized. Loss of Ngb function had no effect on overall circadian entrainment, but resulted in a significantly larger phase delay of circadian rhythm upon light stimulation at early night. A light-induced increase in Per1, but not Fos, gene expression was observed in Ngb-deficient mice. Ngb expressing neurons which co-stored Gastrin Releasing Peptide (GRP) and were innervated from the eye and the geniculo-hypothalamic tract expressed FOS after light stimulation. No PER1 expression was observed in Ngb-positive neurons. The present study demonstrates for the first time that the genetic elimination of Ngb does not affect core clock function but evokes an increased behavioural response to light concomitant with increased Per1 gene expression in the SCN at early night.

  11. 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 (SC

  12. DEFICIENT CUBIC SPLINES WITH AVERAGE SLOPE MATCHING

    Institute of Scientific and Technical Information of China (English)

    V. B. Das; A. Kumar

    2005-01-01

    We obtain a deficient cubic spline function which matches the functions with certain area matching over a greater mesh intervals, and also provides a greater flexibility in replacing area matching as interpolation. We also study their convergence properties to the interpolating functions.

  13. Treatment of Vitamin D deficient states

    Science.gov (United States)

    UpToDate performs a continuous review of over 330 journals and other resources to synthesize and provide the latest medical information for clinicians. Updates are added as important new information is published. This document reviews the prevalence and treatment of vitamin D deficient states. Sever...

  14. Iron and Folate-Deficiency Anaemias.

    Science.gov (United States)

    Hercberg, Serge

    1990-01-01

    Nutritional anemia is believed to be the most widespread nutritional disorder in the world. While it generally affects developing countries, developed countries are also affected to an extent sufficient to justify the implementation of preventive measures at a national level. This report focuses on iron and folate deficiencies, which are by far…

  15. Color Vision Deficiencies in Children. United States.

    Science.gov (United States)

    National Center for Health Statistics (DHEW/PHS), Hyattsville, MD.

    Presented are prevalence data on color vision deficiencies (color blindness) in noninstitutionalized children, aged 6-11, in the United States, as estimated from the Health Examination Survey findings on a representative sample of over 7,400 children. Described are the two color vision tests used in the survey, the Ishihara Test for Color…

  16. 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.

  17. Genetics Home Reference: factor XI deficiency

    Science.gov (United States)

    ... common feature of factor XI deficiency is prolonged bleeding after trauma or surgery, especially involving the inside of the mouth and ... nasal cavities ) or the urinary tract . If the bleeding is left untreated after surgery, solid swellings consisting of congealed blood (hematomas) can ...

  18. Vitamin D deficiency among healthy Egyptian females.

    Science.gov (United States)

    Botros, Raif M; Sabry, Inas M; Abdelbaky, Rania S; Eid, Yara M; Nasr, Merihan S; Hendawy, Laila M

    2015-01-01

    Vitamin D deficiency is becoming endemic in many parts of the world. To study vitamin D status in Egyptian females of different age groups. A cross-sectional study was conducted on 404 females, who were categorized into group 1 (51 nursing females); group 2 (50 pregnant females); group 3 (208 females of childbearing age); group 4 (38 elderly females); and group 5 (57 geriatric females). Females completed a questionnaire regarding dietary calcium and vitamin D intake, sun exposure, and clothing habits, and performed laboratory tests including calcium, PO4, alkaline phosphatase, intact PTH, and 25-OH vitamin D levels. Median and IQR of vitamin D levels across groups 1, 2, 3 and 5 were in the deficient range, being lowest in groups 3, 5, and 1, respectively. Vitamin D deficiency was found in 72.6% of the nursing group, 54% of the pregnant group, 72% of the childbearing age group, 39.5% of the elderly group, and 77.2% of the geriatric group. Vitamin D was significantly higher in non-veiled females [23ng/dl] as compared to veiled females [16.7ng/dl]. Vitamin D levels with poor, fair, and good sun exposure were 14.1, 14, and 37ng/dl, respectively. These results show a high prevalence of vitamin D deficiency among healthy Egyptian females. Copyright © 2015 SEEN. Published by Elsevier España, S.L.U. All rights reserved.

  19. Genetics Home Reference: leptin receptor 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 Disease InfoSearch: Leptin receptor deficiency MalaCards: obesity, morbid, due to leptin ...

  20. Periodic fever and mevalonate kinase deficiency

    NARCIS (Netherlands)

    Frenkel, Joost

    2002-01-01

    Mevalonate kinase (MK) deficiency is an autosomal recessive disorder, caused by mutations in the MVK-gene on chromosome 12q24. The affected enzyme catalyzes an early step in isoprenoid biosynthesis, the pathway that produces cholesterol and several non-sterol isoprenoids. The clinical spectrum inclu

  1. Vitamin A deficiency Ann Burgess MPH

    African Journals Online (AJOL)

    Angel_D

    Mother and child undernutrition – Vitamin A deficiency. Ann Burgess ... (due to impaired transport of iron), poor growth and, in severe cases, xerophthalmia ... Vitamin A occurs mainly as 'retinol' in animal foods and as 'Я-carotene' in plant foods c. ... Vitamin A supplements are usually given orally as high dose capsules.

  2. DEFICIENT FUNCTIONS OF RANDOM DIRICHLET SERIES

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    In this article, the uniqueness theorem of Dirichlet series is proved. Then the random Dirichlet series in the right half plane is studied, and the result that the random Dirichlet series of finite order has almost surely(a.s.) no deficient functions is proved.

  3. Iron-Deficiency Anemia and Stroke

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2007-11-01

    Full Text Available The prevalence of iron-deficiency anemia (IDA in young children at the time of stroke and in age-matched healthy controls was compared in a case-control study conducted at the Hospital for Sick Children, Toronto, Canada.

  4. Genetics Home Reference: color vision deficiency

    Science.gov (United States)

    ... SERIES TRITANOPIA Sources for This Page Deeb SS. Molecular genetics of color-vision deficiencies. Vis Neurosci. 2004 May-Jun;21(3):191-6. Review. Citation on PubMed Deeb SS. The molecular basis of variation in human color vision. Clin Genet. 2005 May;67(5): ...

  5. Morbidity and GH deficiency: a nationwide study

    DEFF Research Database (Denmark)

    Stochholm, K.; Laursen, T.; Green, A.;

    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...

  6. 18 CFR 5.20 - Deficient applications.

    Science.gov (United States)

    2010-04-01

    ... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Deficient applications. 5.20 Section 5.20 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION... competing application, the resubmittal is timely. The date the rejected application is resubmitted will...

  7. Iron and Folate-Deficiency Anaemias.

    Science.gov (United States)

    Hercberg, Serge

    1990-01-01

    Nutritional anemia is believed to be the most widespread nutritional disorder in the world. While it generally affects developing countries, developed countries are also affected to an extent sufficient to justify the implementation of preventive measures at a national level. This report focuses on iron and folate deficiencies, which are by far…

  8. Vitamin D deficiency and heart disease

    NARCIS (Netherlands)

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

    2011-01-01

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

  9. Iron Deficiency in Adolescents and Young Adults.

    Science.gov (United States)

    Risser, William L.; Risser, Jan M. H.

    1990-01-01

    Reviews the prevalence, natural history, causes, impact on performance, diagnosis, and treatment of iron deficiency in adolescent and young adult athletes. All athletes should be screened and treated. The best diagnosis involves determining serum ferritin and hemoglobin levels. Treatment requires therapeutic doses of oral ferrous iron for several…

  10. Genetics Home Reference: triosephosphate isomerase deficiency

    Science.gov (United States)

    ... Oláh J, Ovádi J. Triosephosphate isomerase deficiency: new insights into an enigmatic disease. Biochim Biophys Acta. 2009 ... healthcare professional . About Genetics Home Reference Site Map Customer Support Selection Criteria for Links USA.gov Copyright ...

  11. Iron deficiency in the young athlete.

    Science.gov (United States)

    Rowland, T W

    1990-10-01

    Although overt anemia is uncommon, depletion of body iron stores is common among adolescent female athletes. Poor dietary iron intake, menstruation, and increased iron losses associated with physical training all appear to be important factors. Whether nonanemic iron deficiency can impair exercise performance is uncertain. Nonetheless, athletes with low ferritin levels are at risk for impaired erythropoiesis and should receive therapeutic iron supplementation.

  12. Colour Vision Deficiency and Physics Teaching

    Science.gov (United States)

    Maule, Louise; Featonby, David

    2016-01-01

    1 in 12 males suffer from some form of colour vision deficiency (CVD) which in the present colour dominated world of education presentation can be a severe disadvantage. Although aware of "colourblindness" most teachers make little or no adjustment for these pupils for whom tasks may be more difficult. This article examines colour vision…

  13. [The frequency and development of tissue iron deficiency in 6 iron deficiency anemia patients with plummer-vinson syndrome].

    Science.gov (United States)

    Uchida, T; Matsuno, M; Ide, M; Kawachi, Y

    1998-11-01

    The physical signs of tissue iron deficiency include smooth and red tongue, angular stomatitis, koilonychia, and pica. The incidence of these conditions is unknown in Japan. We evaluated the frequency and development of tissue iron deficiency in 353 patients with iron deficiency anemia. The frequency of tissue iron deficiency was 6.8%; papillary atrophy of the tongue, 5.4%; abnormal nails, 5.4%; angular stomatitis, 1.1%; Plummer-Vinson syndrome, 1.7%; and pica, 0.06%. These findings were compared with the date collected by Wintrobe and Beveridge. The development and incidence of tissue iron deficiency correlated significantly with the severity of iron deficiency anemia.

  14. Prevalence of iron deficiency anemia and iron deficiency in a pediatric population with inflammatory bowel disease

    OpenAIRE

    Carvalho, FS; de Medeiros, IA; Antunes, H.

    2017-01-01

    Iron deficiency is the most common cause of anemia in children with inflammatory bowel disease, although the real prevalence is unknown. Intravenous iron is suggested as the first line treatment. This study aims to determine the prevalence of iron deficiency anemia in children with inflammatory bowel disease followed in a Pediatric Gastroenterology Unit of a tertiary center and to evaluate this unit's experience with intravenous iron. info:eu-repo/semantics/publishedVersion

  15. High Prevalence of Vitamin B12 Deficiency and No Folate Deficiency in Young Children in Nepal

    Directory of Open Access Journals (Sweden)

    Bernadette N. Ng’eno

    2017-01-01

    Full Text Available Many children in low- and middle-income countries may have inadequate intake of vitamin B12 and folate; data confirming these inadequacies are limited. We used biochemical, demographic, behavioral and anthropometric data to describe the folate and vitamin B12 concentrations among six- to 23-month-old Nepalese children. Vitamin B12 (serum B12 < 150 pmol/L and folate deficiencies (red blood cell (RBC folate < 226.5 nmol/L were assessed. We used logistic regression to identify predictors of vitamin B12 deficiency. The vitamin B12 geometric mean was 186 pmol/L; 30.2% of children were deficient. The mean RBC folate concentration was 13,612 nmol/L; there was no deficiency. Factors associated with vitamin B12 deficiency included: (a age six to 11 months (adjusted odds ratio (aOR 1.51; 95% confidence interval (CI: 1.18, 1.92 or 12–17 months (aOR 1.38; 95% CI: 1.10, 1.72 compared to 18–23 months; (b being stunted (aOR 1.24; 95% CI: 1.03, 1.50 compared to not being stunted; (c and not eating animal-source foods (aOR 1.85; 95% CI: 1.42, 2.41 compared to eating animal-source foods the previous day. There was a high prevalence of vitamin B12 deficiency, but no folate deficiency. Improving early feeding practices, including the consumption of rich sources of vitamin B12, such as animal-source foods and fortified foods, may help decrease deficiency.

  16. Vitamin D deficiency in postmenopausal women with pelvic floor disorders

    Directory of Open Access Journals (Sweden)

    Preethi Raja Navaneethan

    2015-01-01

    Conclusion: Findings suggest association of vitamin D deficiency and PFD in postmenopausal women. In addition, postmenopausal women have a high prevalence of vitamin D deficiency indicating a need to evaluate vitamin D levels in these women.

  17. Allergic disease as an association of steroid sulphatase deficiency.

    Science.gov (United States)

    Sakura, N; Nishimura, S; Matsumoto, T; Ohsaki, M; Ogata, T

    1997-11-01

    Ten of 31 patients with steroid sulphatase (STS) deficiency were found to have an allergic disease (bronchial asthma, allergic rhinitis, or atopic dermatitis). STS deficiency may predispose patients to allergic disease.

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

    Directory of Open Access Journals (Sweden)

    Perla Vicari

    2010-06-01

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

  19. Iron deficiency in sports - definition, influence on performance and therapy

    OpenAIRE

    Clénin, German; Cordes, Mareike; Huber, Andreas; Schumacher, Yorck Olaf; Noack, Patrick; Scales, John; Kriemler, Susi

    2015-01-01

    Iron deficiency is frequent among athletes. All types of iron deficiency may affect physical performance and should be treated. The main mechanisms by which sport leads to iron deficiency are increased iron demand, elevated iron loss and blockage of iron absorption due to hepcidin bursts. As a baseline set of blood tests, haemoglobin, haematocrit, mean cellular volume, mean cellular haemoglobin and serum ferritin levels help monitor iron deficiency. In healthy male and female athletes >15 yea...

  20. Secondary Carnitine Deficiency in Dialysis Patients: Shall We Supplement It?

    OpenAIRE

    Wanders, Ronald J. A.; Tim Ulinski; Stephanie E. Reuter; Asha Moudgil

    2016-01-01

    Carnitine, essential for fatty acid β-oxidation, is obtained from diet and through de novo biosynthesis. The organic cation/carnitine transporter 2 (OCTN2) facilitates carnitine cellular transport and kidney resorption. Carnitine depletion occurs in OCTN2-deficient patients, with serious clinical complications including cardiomyopathy, myopathy, and hypoketotic hypoglycaemia. Neonatal screening can detect OCTN2 deficiency. OCTN2-deficiency is also known as primary carnitine deficiency. Carnit...