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Sample records for alpha-1-antitrypsin a1at deficiency

  1. Alpha1-antitrypsin deficiency

    DEFF Research Database (Denmark)

    Stolk, Jan; Seersholm, Niels; Kalsheker, Noor

    2006-01-01

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

  2. Alpha-1-antitrypsin deficiency.

    Science.gov (United States)

    Bals, Robert

    2010-10-01

    Alpha-1-antitrypsin deficiency (AATD) is a rare genetic disorder associated with the development of liver and lung disease. AAT is a 52-kD glycoprotein, produced mainly by hepatocytes and secreted into the blood. Agglomeration of the AAT-protein in hepatocytes can result in liver disease. Exposure to smoke is the major risk factor for the development of lung disease characterised as early chronic obstructive lung disease (COPD). Diagnosis is based on the analysis of the AAT genotype and phenotype. The measurement of the AAT serum level is useful as screening test. Liver biopsy is not necessary to establish the diagnosis. Therapy for AAT-related liver disease is supportive, a specific therapy is not available. AATD is a rare condition (1:5000-10000) and, as a consequence, data and information on diagnosis and treatment are not easily accessible. This chapter provides a comprehensive overview on AATD, covering basic biology, diagnostic and therapeutic approaches. Copyright © 2010 Elsevier Ltd. All rights reserved.

  3. Liver replacement for alpha1-antitrypsin deficiency

    Science.gov (United States)

    Putnam, Charles W.; Porter, Kendrick A.; Peters, Robert L.; Ashcavai, Mary; Redeker, Allan G.; Starzl, Thomas E.

    2010-01-01

    A 16-year-old girl with advanced cirrhosis and severe alpha1-antitrypsin deficiency of the homozygous PiZZ phenotype was treated by orthotopic liver transplantation. After replacement of the liver with a homograft from a donor with the normal PiMM phenotype, the alpha1-antitrypsin concentration in the recipient’s serum rose to normal; it had the PiMM phenotype. Two and a third years later, chronic rejection necessitated retransplantation. Insertion of a homograft from a heterozygous PiMZ donar was followed by the identification of that phenotype in the recipient’s serum. Neither liver graft developed the alpha1-antitrypsin glycoprotein deposits seen with the deficiency state. These observations confirm that this hepatic- based inborn error metabolism is metabolically cured by liver replacement. PMID:320694

  4. Deficiency of a alpha-1-antitrypsin influences systemic iron homeostasis

    Science.gov (United States)

    Abstract Background: There is evidence that proteases and anti-proteases participate in the iron homeostasis of cells and living systems. We tested the postulate that alpha-1 antitrypsin (A1AT) polymorphism and the consequent deficiency of this anti-protease in humans are asso...

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

    Science.gov (United States)

    Gruntman, Alisha M; Flotte, Terence R

    2017-01-01

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

  6. Progression of emphysema evaluated by MRI using hyperpolarized (3)He (HP (3)He) measurements in patients with alpha-1-antitrypsin (A1AT) deficiency compared with CT and lung function tests

    DEFF Research Database (Denmark)

    Stavngaard, T; Søgaard, L Vejby; Batz, M

    2009-01-01

    as compared to yearly decline. PURPOSE: To investigate the progression of emphysema over a period of 2 years using diffusion-weighted hyperpolarized (HP) (3)He magnetic resonance imaging (MRI) in patients with alpha-1-antitrypsin (A1AT) deficiency. MATERIAL AND METHODS: Nine patients with severe A1AT...

  7. Gene therapy for alpha-1 antitrypsin deficiency.

    Science.gov (United States)

    Flotte, Terence R; Mueller, Christian

    2011-04-15

    Alpha-1 antitrypsin (AAT) deficiency is a common single-gene disorder among Northern Europeans and North Americans. The carrier frequency for the common missense mutation (Z-AAT) ranges from 4% in the US to nearly 25% in the Republic of Ireland. Severe AAT deficiency (plasma levels below 11 μm) is most commonly associated with an adult-onset lung disease, with pan-acinar emphysema and airway inflammation, which is thought to be primarily owing to the loss of function of AAT in neutralizing neutrophil elastase and other pro-inflammatory enzymes. In 5-10% of patients, severe liver disease may develop. This may occur at any time from infancy to adulthood, and is thought to be owing to toxicity from the Z-AAT mutant protein that folds poorly and forms insoluble polymers within the hepatocyte, which is the primary site for AAT production. Thus, gene therapy for AAT lung disease is conceived of as augmentation of serum levels (a prolonged form of protein replacement, which is currently in use), while gene therapy for liver disease presents the problem of also having to downregulate the production of Z-AAT protein. Over the years, numerous strategies have been employed for the gene therapy of both AAT-deficient lung disease and liver disease. These will be reviewed with an emphasis on modalities that have reached clinical trials recently.

  8. Alpha-1 Antitrypsin Deficiency (Inherited Emphysema)

    Science.gov (United States)

    ... antitrypsin inactivates elastase once it has finished its job. Without alpha 1 antitrypsin, elastase can destroy the air sacs of the lung. How is the diagnosis made? Because Alpha-1 related disease is COPD, the diagnosis is made by the same methods. Your doctor may have you do a number ...

  9. The prevalence of alpha-1 antitrypsin deficiency in Ireland

    OpenAIRE

    Morris Valerie B; Dimitrov Borislav D; O'Brien Geraldine; Kelleher Dermot P; McPartlin Joseph; Floyd Olwen; O'Connor Catherine A; Carroll Tomás P; Taggart Clifford C; McElvaney Noel G

    2011-01-01

    PUBLISHED Background: Alpha-1 antitrypsin deficiency (AATD) results from mutations in the SERPINA1 gene and classically presents with early-onset emphysema and liver disease. The most common mutation presenting with clinical evidence is the Z mutation, while the S mutation is associated with a milder plasma deficiency. AATD is an under-diagnosed condition and the World Health Organisation recommends targeted detection programmes for AATD in patients with chronic obstructive pulmonary disea...

  10. The promise of gene therapy for the treatment of alpha-1 antitrypsin deficiency.

    Science.gov (United States)

    Cruz, Pedro E; Mueller, Christian; Flotte, Terence R

    2007-09-01

    In the last 13 years, three gene therapy trials for the treatment of alpha-1 antitrypsin deficiency have been conducted. The first trial delivered plasmid encoding the alpha-1 antitrypsin cDNA to the nasal epithelium using cationic liposomes. The last two trials delivered recombinant adeno-associated vectors encoding the alpha-1 antitrypsin cDNA by intramuscular injection. In this review, the progress of ongoing clinical trials and new gene therapy technologies is discussed.

  11. Gene-based therapy for alpha-1 antitrypsin deficiency.

    Science.gov (United States)

    Mueller, Christian; Flotte, Terence R

    2013-03-01

    Alpha-1 antitrypsin Deficiency (AATD) has been an attractive target for the development of gene therapy because it is a common single gene disorder, for which there would appear to be significant benefit to be gained for lung disease patients by augmentation of plasma levels of wild-type (M) alpha-1 antitrypsin (AAT). While a significant proportion of patients also have liver disease, which is unlikely to be benefitted by augmentation, the potential to treat or prevent lung disease by replacement of plasma levels to at least 11 microMolar (571 mcg/ml) is the basis upon which several protein replacement therapies have been licensed for human use. Further enhancing the likelihood of success of gene therapy is the fact that the AAT coding sequence is relatively short and the protein appears to function primarily in the plasma and extracellular space. This means that AAT production from any cell or tissue capable of secreting it could be useful therapeutically for augmentation. Based on these considerations, attempts have been made to develop AAT therapies using nonviral gene transfer, gammaretrovirus, recombinant adenovirus (rAd), and recombinant adeno-associated virus (rAAV) vectors. These have resulted in three phase I clinical trials (one of cationic liposome, one of rAAV2, and one of rAAV1) and one phase II clinical trial (with rAAV1). The results of the latter trial, while promising, demonstrated levels were only 3 to 5% of the target range. This indicates the need to further increase the dose of the vector and/or to increase the levels to within the therapeutic range.

  12. 5 Year Expression and Neutrophil Defect Repair after Gene Therapy in Alpha-1 Antitrypsin Deficiency.

    Science.gov (United States)

    Mueller, Christian; Gernoux, Gwladys; Gruntman, Alisha M; Borel, Florie; Reeves, Emer P; Calcedo, Roberto; Rouhani, Farshid N; Yachnis, Anthony; Humphries, Margaret; Campbell-Thompson, Martha; Messina, Louis; Chulay, Jeffrey D; Trapnell, Bruce; Wilson, James M; McElvaney, Noel G; Flotte, Terence R

    2017-06-07

    Alpha-1 antitrypsin deficiency is a monogenic disorder resulting in emphysema due principally to the unopposed effects of neutrophil elastase. We previously reported achieving plasma wild-type alpha-1 antitrypsin concentrations at 2.5%-3.8% of the purported therapeutic level at 1 year after a single intramuscular administration of recombinant adeno-associated virus serotype 1 alpha-1 antitrypsin vector in alpha-1 antitrypsin deficient patients. We analyzed blood and muscle for alpha-1 antitrypsin expression and immune cell response. We also assayed previously reported markers of neutrophil function known to be altered in alpha-1 antitrypsin deficient patients. Here, we report sustained expression at 2.0%-2.5% of the target level from years 1-5 in these same patients without any additional recombinant adeno-associated virus serotype-1 alpha-1 antitrypsin vector administration. In addition, we observed partial correction of disease-associated neutrophil defects, including neutrophil elastase inhibition, markers of degranulation, and membrane-bound anti-neutrophil antibodies. There was also evidence of an active T regulatory cell response (similar to the 1 year data) and an exhausted cytotoxic T cell response to adeno-associated virus serotype-1 capsid. These findings suggest that muscle-based alpha-1 antitrypsin gene replacement is tolerogenic and that stable levels of M-AAT may exert beneficial neutrophil effects at lower concentrations than previously anticipated. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

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

    DEFF Research Database (Denmark)

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

    2003-01-01

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

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

    Directory of Open Access Journals (Sweden)

    De TOMMASO Adriana Maria Alves

    2001-01-01

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

  15. Cardiovascular risk in patients with alpha-1-antitrypsin deficiency.

    Science.gov (United States)

    Fähndrich, Sebastian; Biertz, Frank; Karch, Annika; Kleibrink, Björn; Koch, Armin; Teschler, Helmut; Welte, Tobias; Kauczor, Hans-Ulrich; Janciauskiene, Sabina; Jörres, Rudolf A; Greulich, Timm; Vogelmeier, Claus F; Bals, Robert

    2017-09-15

    Alpha-1-antitrypsin deficiency (AATD) is a rare inherited condition caused by mutations of the SERPINA1 gene that is associated with the development of a COPD like lung disease. The comorbidities in patients with AATD-related lung diseases are not well defined. The aim of this study was to analyze the clinical phenotype of AATD patients within the German COPD cohort study COSYCONET ("COPD and SYstemic consequences-COmorbidities NETwork") cohort focusing on the distribution of comorbidities. The data from 2645 COSYCONET patients, including 139 AATD patients (110 with and 29 without augmentation therapy), were analyzed by descriptive statistics and regression analyses. We found significantly lower prevalence of cardiovascular comorbidities in AATD patients as compared to non-AATD COPD patients. After correction for age, pack years, body mass index, and sex, the differences were still significant for coronary artery disease (p = 0.002) and the prevalence of peripheral artery disease as determined by an ankle-brachial-index <= 0.9 (p = 0.035). Also the distribution of other comorbidities such as bronchiectasis differed between AATD and non-deficient COPD. AATD is associated with a lower prevalence of cardiovascular disease, the underlying mechanisms need further investigation.

  16. The prevalence of alpha-1 antitrypsin deficiency in Ireland.

    LENUS (Irish Health Repository)

    Carroll, Tomas P

    2012-02-01

    BACKGROUND: Alpha-1 antitrypsin deficiency (AATD) results from mutations in the SERPINA1 gene and classically presents with early-onset emphysema and liver disease. The most common mutation presenting with clinical evidence is the Z mutation, while the S mutation is associated with a milder plasma deficiency. AATD is an under-diagnosed condition and the World Health Organisation recommends targeted detection programmes for AATD in patients with chronic obstructive pulmonary disease (COPD), non-responsive asthma, cryptogenic liver disease and first degree relatives of known AATD patients. METHODS: We present data from the first 3,000 individuals screened following ATS\\/ERS guidelines as part of the Irish National Targeted Detection Programme (INTDP). We also investigated a DNA collection of 1,100 individuals randomly sampled from the general population. Serum and DNA was collected from both groups and mutations in the SERPINA1 gene detected by phenotyping or genotyping. RESULTS: The Irish National Targeted Detection Programme identified 42 ZZ, 44 SZ, 14 SS, 430 MZ, 263 MS, 20 IX and 2 rare mutations. Analysis of 1,100 randomly selected individuals identified 113 MS, 46 MZ, 2 SS and 2 SZ genotypes. CONCLUSION: Our findings demonstrate that AATD in Ireland is more prevalent than previously estimated with Z and S allele frequencies among the highest in the world. Furthermore, our targeted detection programme enriched the population of those carrying the Z but not the S allele, suggesting the Z allele is more important in the pathogenesis of those conditions targeted by the detection programme.

  17. The prevalence of alpha-1 antitrypsin deficiency in Ireland.

    LENUS (Irish Health Repository)

    Carroll, Tomas P

    2011-07-13

    Abstract Background Alpha-1 antitrypsin deficiency (AATD) results from mutations in the SERPINA1 gene and classically presents with early-onset emphysema and liver disease. The most common mutation presenting with clinical evidence is the Z mutation, while the S mutation is associated with a milder plasma deficiency. AATD is an under-diagnosed condition and the World Health Organisation recommends targeted detection programmes for AATD in patients with chronic obstructive pulmonary disease (COPD), non-responsive asthma, cryptogenic liver disease and first degree relatives of known AATD patients. Methods We present data from the first 3,000 individuals screened following ATS\\/ERS guidelines as part of the Irish National Targeted Detection Programme (INTDP). We also investigated a DNA collection of 1,100 individuals randomly sampled from the general population. Serum and DNA was collected from both groups and mutations in the SERPINA1 gene detected by phenotyping or genotyping. Results The Irish National Targeted Detection Programme identified 42 ZZ, 44 SZ, 14 SS, 430 MZ, 263 MS, 20 IX and 2 rare mutations. Analysis of 1,100 randomly selected individuals identified 113 MS, 46 MZ, 2 SS and 2 SZ genotypes. Conclusion Our findings demonstrate that AATD in Ireland is more prevalent than previously estimated with Z and S allele frequencies among the highest in the world. Furthermore, our targeted detection programme enriched the population of those carrying the Z but not the S allele, suggesting the Z allele is more important in the pathogenesis of those conditions targeted by the detection programme.

  18. Deficiency Mutations of Alpha-1 Antitrypsin. Effects on Folding, Function, and Polymerization.

    Science.gov (United States)

    Haq, Imran; Irving, James A; Saleh, Aarash D; Dron, Louis; Regan-Mochrie, Gemma L; Motamedi-Shad, Neda; Hurst, John R; Gooptu, Bibek; Lomas, David A

    2016-01-01

    Misfolding, polymerization, and defective secretion of functional alpha-1 antitrypsin underlies the predisposition to severe liver and lung disease in alpha-1 antitrypsin deficiency. We have identified a novel (Ala336Pro, Baghdad) deficiency variant and characterized it relative to the wild-type (M) and Glu342Lys (Z) alleles. The index case is a homozygous individual of consanguineous parentage, with levels of circulating alpha-1 antitrypsin in the moderate deficiency range, but is a biochemical phenotype that could not be classified by standard methods. The majority of the protein was present as functionally inactive polymer, and the remaining monomer was 37% active relative to the wild-type protein. These factors combined indicate an 85 to 95% functional deficiency, similar to that seen with ZZ homozygotes. Biochemical, biophysical, and computational studies further defined the molecular basis of this deficiency. These studies demonstrated that native Ala336Pro alpha-1 antitrypsin could populate the polymerogenic intermediate-and therefore polymerize-more readily than either wild-type alpha-1 antitrypsin or the Z variant. In contrast, folding was far less impaired in Ala336Pro alpha-1 antitrypsin than in the Z variant. The data are consistent with a disparate contribution by the "breach" region and "shutter" region of strand 5A to folding and polymerization mechanisms. Moreover, the findings demonstrate that, in these variants, folding efficiency does not correlate directly with the tendency to polymerize in vitro or in vivo. They therefore differentiate generalized misfolding from polymerization tendencies in missense variants of alpha-1 antitrypsin. Clinically, they further support the need to quantify loss-of-function in alpha-1 antitrypsin deficiency to individualize patient care.

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

    Directory of Open Access Journals (Sweden)

    Caitriona McLean

    2009-01-01

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

  20. Alpha-1 Antitrypsin Deficiency Targeted Testing and Augmentation Therapy: A Canadian Thoracic Society Clinical Practice Guideline

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    DD Marciniuk

    2012-01-01

    Full Text Available Alpha-1 antitrypsin (A1AT functions primarily to inhibit neutrophil elastase, and deficiency predisposes individuals to the development of chronic obstructive pulmonary disease (COPD. Severe A1AT deficiency occurs in one in 5000 to one in 5500 of the North American population. While the exact prevalence of A1AT deficiency in patients with diagnosed COPD is not known, results from small studies provide estimates of 1% to 5%. The present document updates a previous Canadian Thoracic Society position statement from 2001, and was initiated because of lack of consensus and understanding of appropriate patients suitable for targeted testing for A1AT deficiency, and for the use of A1AT augmentation therapy. Using revised guideline development methodology, the present clinical practice guideline document systematically reviews the published literature and provides an evidence-based update. The evidence supports the practice that targeted testing for A1AT deficiency be considered in individuals with COPD diagnosed before 65 years of age or with a smoking history of <20 pack years. The evidence also supports consideration of A1AT augmentation therapy in nonsmoking or exsmoking patients with COPD (forced expiratory volume in 1 s of 25% to 80% predicted attributable to emphysema and documented A1AT deficiency (level ≤11 μmol/L who are receiving optimal pharmacological and nonpharmacological therapies (including comprehensive case management and pulmonary rehabilitation because of benefits in computed tomography scan lung density and mortality.

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

    LENUS (Irish Health Repository)

    McLean, Caitriona

    2009-01-01

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

  2. Progress with Recombinant Adeno-Associated Virus Vectors for Gene Therapy of Alpha-1 Antitrypsin Deficiency.

    Science.gov (United States)

    Gruntman, Alisha M; Flotte, Terence R

    2015-06-01

    The pathway to a clinical gene therapy product often involves many changes of course and strategy before obtaining successful results. Here we outline the methodologies, both clinical and preclinical, that went into developing a gene therapy approach to the treatment of alpha-1 antitrypsin deficiency lung disease using muscle-targeted recombinant adeno-associated virus. From initial gene construct development in mouse models through multiple rounds of safety and biodistribution studies in rodents, rabbits, and nonhuman primates to ultimate human trials, this review seeks to provide insight into what clinical translation entails and could thereby inform the process for future investigators.

  3. Prevalence of alpha-1 antitrypsin deficiency and allele frequency in patients with COPD in Brazil

    OpenAIRE

    Russo, Rodrigo; Zillmer, Laura Russo; Nascimento, Oliver Augusto; Manzano, Beatriz; Ivanaga, Ivan Teruaki; Fritscher, Leandro; Lundgren, Fernando; Miravitlles, Marc; Gondim, Heicilainy Del Carlos; Santos Junior, Gildo; Alves, Marcela Amorim; Oliveira, Maria Vera; Souza, Altay Alves Lino de; Sales, Maria Penha Uchoa; Jardim, José Roberto

    2016-01-01

    ABSTRACT Objective: To determine the prevalence of alpha 1-antitrypsin (AAT) deficiency (AATD), as well as allele frequency, in COPD patients in Brazil. Methods: This was a cross-sectional study involving 926 COPD patients 40 years of age or older, from five Brazilian states. All patients underwent determination of AAT levels in dried blood spot (DBS) samples by nephelometry. Those with DBS AAT levels ≤ 2.64 mg/dL underwent determination of serum AAT levels. Those with serum AAT levels of <...

  4. Prognosis of patients with alpha1-antitrypsine deficiency on long-term oxygen therapy

    DEFF Research Database (Denmark)

    Ringbaek, Thomas J; Seersholm, Niels; Perch, Michael

    2014-01-01

    : Compared with COPD without AATD, AATD patients are younger, more often males, have a lower prevalence of cardio-vascular diseases and diabetes mellitus, and higher prevalence of osteoporosis. Moreover, they have better prognosis, partly due to greater chance of receiving a lung transplantation....... on average about 17 years younger than patients without AATD. Cardio-vascular diseases and diabetes mellitus were significantly less prevalent among patients with AATD (60.4% versus 70.3% (P ...INTRODUCTION: Data on patients with alpha1-antitrypsine deficiency (AATD) on long-term oxygen therapy (LTOT) is sparse. The aim of this study was to present the incidence of patients with AATD on LTOT, and compare their characteristics, comorbidities and prognosis (lung transplantation, termination...

  5. Diagnosing alpha-1 antitrypsin deficiency: the first step in precision medicine [version 1; referees: 3 approved

    Directory of Open Access Journals (Sweden)

    Craig P. Hersh

    2017-11-01

    Full Text Available Severe alpha-1 antitrypsin (AAT deficiency is one of the most common serious genetic diseases in adults of European descent. Individuals with AAT deficiency have a greatly increased risk for emphysema and liver disease. Other manifestations include bronchiectasis, necrotizing panniculitis and granulomatosis with polyangiitis. Despite the frequency and potential severity, AAT deficiency remains under-recognized, and there is often a delay in diagnosis. This review will focus on three recent updates that should serve to encourage testing and diagnosis of AAT deficiency: first, the publication of a randomized clinical trial demonstrating the efficacy of intravenous augmentation therapy in slowing the progression of emphysema in AAT deficiency; second, the mounting evidence showing an increased risk of lung disease in heterozygous PI MZ genotype carriers; last, the recent publication of a clinical practice guideline, outlining diagnosis and management. Though it has been recognized for more than fifty years, AAT deficiency exemplifies the modern paradigm of precision medicine, with a diagnostic test that identifies a genetic subtype of a heterogeneous disease, leading to a targeted treatment.

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

    Science.gov (United States)

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

    2009-10-01

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

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

    LENUS (Irish Health Repository)

    Kelly, Emer

    2009-06-19

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

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

    Directory of Open Access Journals (Sweden)

    Edgar RG

    2017-05-01

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

  9. Evidence for unfolded protein response activation in monocytes from individuals with alpha-1 antitrypsin deficiency.

    LENUS (Irish Health Repository)

    Carroll, Tomás P

    2010-04-15

    The hereditary disorder alpha-1 antitrypsin (AAT) deficiency results from mutations in the SERPINA1 gene and presents with emphysema in young adults and liver disease in childhood. The most common form of AAT deficiency occurs because of the Z mutation, causing the protein to fold aberrantly and accumulate in the endoplasmic reticulum (ER). This leads to ER stress and contributes significantly to the liver disease associated with the condition. In addition to hepatocytes, AAT is also synthesized by monocytes, neutrophils, and epithelial cells. In this study we show for the first time that the unfolded protein response (UPR) is activated in quiescent monocytes from ZZ individuals. Activating transcription factor 4, X-box binding protein 1, and a subset of genes involved in the UPR are increased in monocytes from ZZ compared with MM individuals. This contributes to an inflammatory phenotype with ZZ monocytes exhibiting enhanced cytokine production and activation of the NF-kappaB pathway when compared with MM monocytes. In addition, we demonstrate intracellular accumulation of AAT within the ER of ZZ monocytes. These are the first data showing that Z AAT protein accumulation induces UPR activation in peripheral blood monocytes. These findings change the current paradigm regarding lung inflammation in AAT deficiency, which up until now was derived from the protease-anti-protease hypothesis, but which now must include the exaggerated inflammatory response generated by accumulated aberrantly folded AAT in circulating blood cells.

  10. In vivo genome editing partially restores alpha1-antitrypsin in a murine model of AAT deficiency.

    Science.gov (United States)

    Song, Chun-Qing; Wang, Dan; Jiang, Tingting; O'Connor, Kevin; Tang, Qiushi; Cai, Lingling; Li, Xiangrui; Weng, Zhiping; Yin, Hao; Gao, Guangping; Mueller, Christian; Flotte, Terence R; Xue, Wen

    2018-03-29

    CRISPR genome editing holds promise in the treatment of genetic diseases that currently lack effective long-term therapies. Patients with Alpha-1 Antitrypsin (AAT) deficiency develop progressive lung disease due to the loss of AAT's antiprotease function and liver disease due to a toxic gain of function of the common mutant allele. However, it remains unknown whether CRISPR-mediated AAT correction in the liver, where AAT is primarily expressed, can correct either or both defects. Here we show that AAV delivery of CRISPR can effectively correct Z-AAT mutation in the liver of a transgenic mouse model. Specifically, we co-injected two AAV: one expressing Cas9 and another encoding an AAT guide RNA and homology-dependent repair template. In both neonate and adult mice, this treatment partially restored M-AAT in the serum. Furthermore, deep sequencing confirmed both indel mutations and precise gene correction in the liver, permitting careful analysis of gene editing events in vivo. This study demonstrates a proof-of-concept for the application of CRISPR-Cas9 technology to correct AAT mutations in vivo and validates continued exploration of this approach for the treatment of patients with AAT deficiency.

  11. Sex differences in alpha-1-antitrypsin deficiency lung disease-analysis from the German registry.

    Science.gov (United States)

    Fähndrich, Sebastian; Herr, Christian; Greulich, Timm; Seibert, Martina; Lepper, Philipp M; Bernhard, Nikolas; Lützow, Cindy; Vogelmeier, Claus; Bals, Robert

    2015-05-01

    Alpha-1-antitrypsin deficiency (AATD) is a rare condition with clinical manifestations of the lung and the liver. There is evidence that the gender affects the clinical presentation of non-AATD chronic obstructive lung disease (COPD). The aim of this study was to analyze gender-dependent disease pattern in AATD-based COPD. Data from 1066 individuals from the German AATD registry were analyzed by descriptive and analytical statistics. The AAT genotypes comprised 820 individuals with PiZZ (male 56%, female 45%), 109 with PI SZ (male 55%; female 45%), and others (n = 137). A subgroup of 422 patients with available post-bronchodilator FEV1% predicted was analyzed in detail after stratification in spirometric GOLD stages I-IV. The age of the registered individuals is 52.2 ± 13.4 years (male: 51.91 ± 13.86 years; female: 52.76 ± 13.39 years). Female patients with GOLD I-IV showed lower numbers of pack-years and lower BMI. The time between the first symptom and the establishment of the correct diagnosis was significantly longer in female (14.47 ± 16.46 years) as compared to male individuals (12.39 ± - 14.38 years, p = 0.04). In conclusion, the data of the registry allow to characterize the natural course of the disease and highlight differences in the clinical presentation of patients with AATD-dependent COPD.

  12. Prevalence of alpha-1 antitrypsin deficiency and allele frequency in patients with COPD in Brazil.

    Science.gov (United States)

    Russo, Rodrigo; Zillmer, Laura Russo; Nascimento, Oliver Augusto; Manzano, Beatriz; Ivanaga, Ivan Teruaki; Fritscher, Leandro; Lundgren, Fernando; Miravitlles, Marc; Gondim, Heicilainy Del Carlos; Santos, Gildo; Alves, Marcela Amorim; Oliveira, Maria Vera; Souza, Altay Alves Lino de; Sales, Maria Penha Uchoa; Jardim, José Roberto

    2016-01-01

    To determine the prevalence of alpha 1-antitrypsin (AAT) deficiency (AATD), as well as allele frequency, in COPD patients in Brazil. This was a cross-sectional study involving 926 COPD patients 40 years of age or older, from five Brazilian states. All patients underwent determination of AAT levels in dried blood spot (DBS) samples by nephelometry. Those with DBS AAT levels ≤ 2.64 mg/dL underwent determination of serum AAT levels. Those with serum AAT levels of sangue seco por meio de nefelometria. Aqueles em que a concentração de AAT no sangue seco foi ≤ 2,64 mg/dl foram submetidos a dosagem sérica de AAT. Aqueles em que a concentração sérica de AAT foi sangue seco ≤ 2,64 mg/dl, e 24 (2,6% da amostra) apresentaram concentração sérica de AAT < 113 mg/dl. A distribuição genotípica nesse subgrupo de 24 pacientes foi a seguinte: PI*MS, em 3 (12,5%); PI*MZ, em 13 (54,2%); PI*SZ, em 1 (4,2%); PI*SS, em 1 (4,2%); e PI*ZZ, em 6 (25,0%). Na amostra estudada, a prevalência global da deficiência de AAT foi de 2,8% e a prevalência do genótipo PI*ZZ (deficiência grave de AAT) foi de 0,8%. A prevalência da deficiência de AAT em pacientes com DPOC no Brasil é semelhante àquela encontrada na maioria dos países e reforça a recomendação de que se deve medir a concentração de AAT em todos pacientes com DPOC.

  13. Serum Proteins Associated with Emphysema Progression in Severe Alpha-1 Antitrypsin Deficiency.

    Science.gov (United States)

    Beiko, Tatsiana; Janech, Michael G; Alekseyenko, Alexander V; Atkinson, Carl; Coxson, Harvey O; Barth, Jeremy L; Stephenson, Sarah E; Wilson, Carole L; Schnapp, Lynn M; Barker, Alan; Brantly, Mark; Sandhaus, Robert A; Silverman, Edwin K; Stoller, James K; Trapnell, Bruce; Charlie, Strange

    2017-07-15

    Computed tomography (CT) lung density is an accepted biomarker for emphysema in alpha-1 antitrypsin deficiency (AATD), although concerns for radiation exposure limit its longitudinal use. Serum proteins associated with emphysema, particularly in early disease, may provide additional pathogenic insights. We investigated whether distinct proteomic signatures characterize the presence and progression of emphysema in individuals with severe AATD and normal forced expiratory volume in 1 second (FEV 1 ). QUANT itative lung CT U n M asking emphysema progression in AATD (QUANTUM-1) is a multicenter, prospective 3-year study of 49 adults with severe AATD and FEV 1 post-bronchodilator values (Post-BD) ≥ 80% predicted. All participants received chest CT, serial spirometry, and contributed to the serum biobank. Volumetric imaging display and analysis (VIDA) software defined the baseline 15 th percentile density (PD15) which was indexed to CT-derived total lung capacity (TLC). We measured 317 proteins using a multiplexed immunoassay (Myriad Discovery MAP ® panel) in 31 individuals with a complete dataset. We analyzed associations between initial PD15/TLC, PD15/TLC annual decline, body mass index (BMI), and protein levels using Pearson's product moment correlation. C-reactive protein (CRP), adipocyte fatty acid-binding protein (AFBP), leptin, and tissue plasminogen activator (tPA) were found to be associated with baseline emphysema and all but leptin were associated with emphysema progression after adjustments were made for age and sex. All 4 proteins were associated with BMI after further adjustment for multiple comparisons was made. The relationship between these proteins and BMI, and further validation of these findings in replicative cohorts require additional studies.

  14. Prevalence of alpha-1 antitrypsin deficiency and allele frequency in patients with COPD in Brazil

    Science.gov (United States)

    Russo, Rodrigo; Zillmer, Laura Russo; Nascimento, Oliver Augusto; Manzano, Beatriz; Ivanaga, Ivan Teruaki; Fritscher, Leandro; Lundgren, Fernando; Miravitlles, Marc; Gondim, Heicilainy Del Carlos; Santos, Gildo; Alves, Marcela Amorim; Oliveira, Maria Vera; de Souza, Altay Alves Lino; Sales, Maria Penha Uchoa; Jardim, José Roberto

    2016-01-01

    ABSTRACT Objective: To determine the prevalence of alpha 1-antitrypsin (AAT) deficiency (AATD), as well as allele frequency, in COPD patients in Brazil. Methods: This was a cross-sectional study involving 926 COPD patients 40 years of age or older, from five Brazilian states. All patients underwent determination of AAT levels in dried blood spot (DBS) samples by nephelometry. Those with DBS AAT levels ≤ 2.64 mg/dL underwent determination of serum AAT levels. Those with serum AAT levels of < 113 mg/dL underwent genotyping. In case of conflicting results, SERPINA1 gene sequencing was performed. Results: Of the 926 COPD patients studied, 85 had DBS AAT levels ≤ 2.64 mg/dL, and 24 (2.6% of the study sample) had serum AAT levels of < 113 mg/dL. Genotype distribution in this subset of 24 patients was as follows: PI*MS, in 3 (12.5%); PI*MZ, in 13 (54.2%); PI*SZ, in 1 (4.2%); PI*SS, in 1 (4.2%); and PI*ZZ, in 6 (25.0%). In the sample as a whole, the overall prevalence of AATD was 2.8% and the prevalence of the PI*ZZ genotype (severe AATD) was 0.8% Conclusions: The prevalence of AATD in COPD patients in Brazil is similar to that found in most countries and reinforces the recommendation that AAT levels be measured in all COPD patients. PMID:27812629

  15. Deficiência de alfa-1 antitripsina: diagnóstico e tratamento Alpha-1 antitrypsin deficiency: diagnosis and treatment

    Directory of Open Access Journals (Sweden)

    Aquiles A Camelier

    2008-07-01

    Full Text Available A deficiência de alfa-1 antitripsina é um distúrbio genético de descoberta recente e que ocorre com freqüência comparável à da fibrose cística. Resulta de diferentes mutações no gene SERPINA1 e tem diversas implicações clínicas. A alfa-1 antitripsina é produzida principalmente no fígado e atua como uma antiprotease. Tem como principal função inativar a elastase neutrofílica, impedindo a ocorrência de dano tecidual. A mutação mais freqüentemente relacionada à doença clínica é o alelo Z, que determina polimerização e acúmulo dentro dos hepatócitos. O acúmulo e a conseqüente redução dos níveis séricos de alfa-1 antitripsina determinam, respectivamente, doença hepática e pulmonar, sendo que esta se manifesta principalmente sob a forma de enfisema de aparecimento precoce, habitualmente com predomínio basal. O diagnóstico envolve a detecção de níveis séricos reduzidos de alfa-1 antitripsina e a confirmação fenotípica. Além do tratamento usual para doença pulmonar obstrutiva crônica, existe atualmente uma terapia específica com infusão de concentrados de alfa-1 antitripsina. Essa terapia de reposição, aparentemente segura, ainda não teve a eficácia clínica definitivamente comprovada, e o custo-efetividade também é um tema controverso e ainda pouco abordado. Apesar da sua importância, não existem dados epidemiológicos brasileiros a respeito da prevalência da doença ou da freqüência de ocorrência dos alelos deficientes. O subdiagnóstico também tem sido uma importante limitação tanto para o estudo da doença quanto para o tratamento adequado dos pacientes. Espera-se que a criação do Registro Internacional de Alfa-1 venha a resolver essas e outras importantes questões.Alpha-1 antitrypsin deficiency is a recently identified genetic disease that occurs almost as frequently as cystic fibrosis. It is caused by various mutations in the SERPINA1 gene, and has numerous clinical

  16. Long-term evolution of lung function in individuals with alpha-1 antitrypsin deficiency from the Spanish registry (REDAAT

    Directory of Open Access Journals (Sweden)

    Esquinas C

    2018-03-01

    Full Text Available Cristina Esquinas,1,2,* Sonia Serreri,3,* Miriam Barrecheguren,1 Esther Rodriguez,1 Alexa Nuñez,1 Francisco Casas-Maldonado,4 Ignacio Blanco,5 Pietro Pirina,3 Beatriz Lara,6 Marc Miravitlles1,7 1Pneumology Department, University Hospital Vall d’Hebron, Barcelona, Spain; 2Public Health, Mental, Maternal and Child Health Nursing Department, Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain; 3Università di Sassari, Sassari, Italy; 4Pneumology Department, University Hospital San Cecilio, Granada, Spain; 5Alpha-1 Antitrypsin Deficiency Spanish Registry (REDAAT, Spanish Society of Pneumology (SEPAR, Barcelona, Spain; 6Coventry and Warwickshire University Hospital, Coventry, UK; 7CIBER de Enfermedades Respiratorias (CIBERES, Spain *These authors contributed equally to this work Background: The clinical course of alpha-1 antitrypsin deficiency (AATD is very heterogeneous. It is estimated that 60% of individuals with severe AATD (Pi*ZZ develop emphysema. The main objective of this study was to describe the outcomes of long-term lung function in individuals with AATD-associated emphysema after at least 8 years of follow-up. Materials and methods: We performed a retrospective analysis of longitudinal follow-up data of AATD PiZZ patients from the Spanish registry (AATD Spanish Registry [REDAAT]. The main follow-up outcome was the annual rate of decline in forced expiratory volume in 1 second (FEV1 calculated using the FEV1 values at baseline and in the last post-bronchodilator spirometry available. Results: One hundred and twenty-two AATD PiZZ patients were analyzed. The median follow-up was 11 years (interquartile range =9–14. The mean FEV1 decline was 28 mL/year (SD=54, with a median of 33 mL/year. Tobacco consumption (β=19.8, p<0.001, previous pneumonia (β=27.8, p=0.026 and higher baseline FEV1% (β=0.798, p=0.016 were independently related to a faster FEV1 decline. Conclusion: In this large cohort with a long

  17. Exploring the role of CT densitometry: a randomised study of augmentation therapy in alpha1-antitrypsin deficiency

    DEFF Research Database (Denmark)

    Dirksen, A; Piitulainen, E; Parr, D G

    2009-01-01

    Assessment of emphysema-modifying therapy is difficult, but newer outcome measures offer advantages over traditional methods. The EXAcerbations and Computed Tomography scan as Lung End-points (EXACTLE) trial explored the use of computed tomography (CT) densitometry and exacerbations...... for the assessment of the therapeutic effect of augmentation therapy in subjects with alpha(1)-antitrypsin (alpha(1)-AT) deficiency. In total, 77 subjects (protease inhibitor type Z) were randomised to weekly infusions of 60 mg x kg(-1) human alpha(1)-AT (Prolastin) or placebo for 2-2.5 yrs. The primary end...... was unaltered by treatment, but a reduction in exacerbation severity was observed. In patients with alpha(1)-AT deficiency, CT is a more sensitive outcome measure of emphysema-modifying therapy than physiology and health status, and demonstrates a trend of treatment benefit from alpha(1)-AT augmentation....

  18. Three new alpha1-antitrypsin deficiency variants help to define a C-terminal region regulating conformational change and polymerization.

    Directory of Open Access Journals (Sweden)

    Anna M Fra

    Full Text Available Alpha1-antitrypsin (AAT deficiency is a hereditary disorder associated with reduced AAT plasma levels, predisposing adults to pulmonary emphysema. The most common genetic AAT variants found in patients are the mildly deficient S and the severely deficient Z alleles, but several other pathogenic rare alleles have been reported. While the plasma AAT deficiency is a common trait of the disease, only a few AAT variants, including the prototypic Z AAT and some rare variants, form cytotoxic polymers in the endoplasmic reticulum of hepatocytes and predispose to liver disease. Here we report the identification of three new rare AAT variants associated to reduced plasma levels and characterize their molecular behaviour in cellular models. The variants, called Mpisa (Lys259Ile, Etaurisano (Lys368Glu and Yorzinuovi (Pro391His, showed reduced secretion compared to control M AAT, and accumulated to different extents in the cells as ordered polymeric structures resembling those formed by the Z variant. Structural analysis of the mutations showed that they may facilitate polymerization both by loosening 'latch' interactions constraining the AAT reactive loop and through effects on core packing. In conclusion, the new AAT deficiency variants, besides increasing the risk of lung disease, may predispose to liver disease, particularly if associated with the common Z variant. The new mutations cluster structurally, thus defining a region of the AAT molecule critical for regulating its conformational state.

  19. Alpha-1 antitrypsin deficiency caused by a novel mutation (p.Leu263Pro: Pi*ZQ0gaia – Q0gaia allele

    Directory of Open Access Journals (Sweden)

    M.J. Oliveira

    2015-11-01

    Full Text Available Severe alpha-1 antitrypsin deficiency (AATD is generally associated with PI*ZZ genotype and less often with combinations of PI*Z, PI*S, and other rarer deficiency or null (Q0 alleles. Severe AATD predisposes patients to various diseases, including pulmonary emphysema. Presented here is a case report of a young man with COPD and AATD. The investigation of the AATD showed a novel mutation p.Leu263Pro (c.860T>C, which was named Q0gaia (Pi*ZQ0gaia. Q0gaia is associated with very low or no detectable serum concentrations of AAT. Keywords: Alpha-1 antitrypsin deficiency, Null allele, COPD

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

    Directory of Open Access Journals (Sweden)

    Darren N Saunders

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

  1. Characteristics of candidates for lung transplantation due to chronic obstructive pulmonary disease and alpha-1 antitrypsin deficiency emphysema.

    Science.gov (United States)

    Giacoboni, Daniela; Barrecheguren, Miriam; Esquinas, Cristina; Rodríguez, Esther; Berastegui, Cristina; López-Meseguer, Manuel; Monforte, Víctor; Bravo, Carlos; Pirina, Pietro; Miravitlles, Marc; Román, Antonio

    2015-08-01

    COPD and emphysema due to alpha-1 antitrypsin deficiency (AATD) are the first and fourth indications for lung transplantation worldwide, respectively. Despite this, there is little information regarding the health status of these patients at the time of transplantation. Patients who received a lung transplant in the Hospital Vall d'Hebron between July 1993 and August 2013 were identified and data from the evaluation prior to the transplant were collected. A total of 217 patients who received a lung transplant for COPD and 19 in whom the indication was AATD were included. These patients were severely impaired at the time of the evaluation for lung transplantation, although the trend in recent years has been to evaluate patients at earlier stages of the disease. Baseline characteristics were similar in both groups except that patients with AATD were younger [43 (7.7) vs. 53.6 (6.1) years old, P<.001], with less exposure to tobacco [23.9 (15) vs. 50 (29) packs-year, P<002] and lower PCO2 [41.7 (7.6) vs. 47.9 (9.7) mmHg, P<.004]. The number of patients receiving a lung transplant for COPD has progressively increased and the tendency is to perform the evaluation in earlier stages of the disease. Patients receiving transplants for COPD and AATD had similar characteristics at the time of the evaluation, although AATD patients were younger and had less exposure to tobacco and lower PCO2. Copyright © 2014 SEPAR. Published by Elsevier Espana. All rights reserved.

  2. Rationale and Design of the Genomic Research in Alpha-1 Antitrypsin Deficiency and Sarcoidosis (GRADS) Study. Sarcoidosis Protocol.

    Science.gov (United States)

    Moller, David R; Koth, Laura L; Maier, Lisa A; Morris, Alison; Drake, Wonder; Rossman, Milton; Leader, Joseph K; Collman, Ronald G; Hamzeh, Nabeel; Sweiss, Nadera J; Zhang, Yingze; O'Neal, Scott; Senior, Robert M; Becich, Michael; Hochheiser, Harry S; Kaminski, Naftali; Wisniewski, Stephen R; Gibson, Kevin F

    2015-10-01

    Sarcoidosis is a systemic disease characterized by noncaseating granulomatous inflammation with tremendous clinical heterogeneity and uncertain pathobiology and lacking in clinically useful biomarkers. The Genomic Research in Alpha-1 Antitrypsin Deficiency and Sarcoidosis (GRADS) study is an observational cohort study designed to explore the role of the lung microbiome and genome in these two diseases. This article describes the design and rationale for the GRADS study sarcoidosis protocol. The study addresses the hypothesis that distinct patterns in the lung microbiome are characteristic of sarcoidosis phenotypes and are reflected in changes in systemic inflammatory responses as measured by peripheral blood changes in gene transcription. The goal is to enroll 400 participants, with a minimum of 35 in each of 9 clinical phenotype subgroups prioritized by their clinical relevance to understanding of the pathobiology and clinical heterogeneity of sarcoidosis. Participants with a confirmed diagnosis of sarcoidosis undergo a baseline visit with self-administered questionnaires, chest computed tomography, pulmonary function tests, and blood and urine testing. A research or clinical bronchoscopy with a research bronchoalveolar lavage will be performed to obtain samples for genomic and microbiome analyses. Comparisons will be made by blood genomic analysis and with clinical phenotypic variables. A 6-month follow-up visit is planned to assess each participant's clinical course. By the use of an integrative approach to the analysis of the microbiome and genome in selected clinical phenotypes, the GRADS study is powerfully positioned to inform and direct studies on the pathobiology of sarcoidosis, identify diagnostic or prognostic biomarkers, and provide novel molecular phenotypes that could lead to improved personalized approaches to therapy for sarcoidosis.

  3. Fluphenazine reduces proteotoxicity in C. elegans and mammalian models of alpha-1-antitrypsin deficiency.

    Directory of Open Access Journals (Sweden)

    Jie Li

    Full Text Available The classical form of α1-antitrypsin deficiency (ATD is associated with hepatic fibrosis and hepatocellular carcinoma. It is caused by the proteotoxic effect of a mutant secretory protein that aberrantly accumulates in the endoplasmic reticulum of liver cells. Recently we developed a model of this deficiency in C. elegans and adapted it for high-content drug screening using an automated, image-based array scanning. Screening of the Library of Pharmacologically Active Compounds identified fluphenazine (Flu among several other compounds as a drug which reduced intracellular accumulation of mutant α1-antitrypsin Z (ATZ. Because it is representative of the phenothiazine drug class that appears to have autophagy enhancer properties in addition to mood stabilizing activity, and can be relatively easily re-purposed, we further investigated its effects on mutant ATZ. The results indicate that Flu reverses the phenotypic effects of ATZ accumulation in the C. elegans model of ATD at doses which increase the number of autophagosomes in vivo. Furthermore, in nanomolar concentrations, Flu enhances the rate of intracellular degradation of ATZ and reduces the cellular ATZ load in mammalian cell line models. In the PiZ mouse model Flu reduces the accumulation of ATZ in the liver and mediates a decrease in hepatic fibrosis. These results show that Flu can reduce the proteotoxicity of ATZ accumulation in vivo and, because it has been used safely in humans, this drug can be moved rapidly into trials for liver disease due to ATD. The results also provide further validation for drug discovery using C. elegans models that can be adapted to high-content drug screening platforms and used together with mammalian cell line and animal models.

  4. Improving adherence to alpha-1 antitrypsin deficiency screening guidelines using the pulmonary function laboratory

    Directory of Open Access Journals (Sweden)

    Luna Diaz LV

    2017-07-01

    Full Text Available Landy V Luna Diaz,1 Isabella Iupe,1 Bruno Zavala,1 Kira C Balestrini,1 Andrea Guerrero,1 Gregory Holt,1,2 Rafael Calderon-Candelario,1,2 Mehdi Mirsaeidi,1,2 Michael Campos1,21Miami Veterans Administration Medical Center, Miami, FL, 2Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, University of Miami School of Medicine, Miami, FL, USAAlpha-1 antitrypsin deficiency (AATD is the only well-recognized genetic disorder associated with an increased risk of emphysema and COPD.1 Identifying AATD allows genetic counseling and the chance to offer specific augmentation therapy to slow emphysema progression. Despite specific recommendations from the World Health Organization, American Thoracic Society and European Respiratory Society to screen all patients with COPD and other at-risk conditions,2–4 testing rates are low (<15%.5We conducted a project to improve AATD screening at the Miami VA Medical Center using the pulmonary function test (PFT laboratory. We instructed the PFT personnel to perform reflex testing on all patients with pre-bronchodilator airflow obstruction (forced expiratory volume in 1 second/forced vital capacity <70% and then evaluated if the screening was appropriate according to guidelines. Trained PFT personnel explained AATD disease to patients and provided them with an informational brochure. After obtaining verbal consent, AATD screening was performed using dried blood spot kits provided by the Alpha-1 Foundation as part of the Florida Screening Program (noncommercial.6 The PFT lab director was the responsible physician of record, in charge of discussing positive results to patients and documenting results in the electronic medical record. The Miami Veterans Affairs Medical Center Institutional Review Board approved the protocol as a quality improvement project.

  5. Association of polymorphism in the alpha-1-antitrypsin gene with ...

    African Journals Online (AJOL)

    Sahand Rayaneh

    2014-06-11

    Jun 11, 2014 ... Association of polymorphism in the alpha-1-antitrypsin gene with milk production traits in ... Abstract. Alpha-1-antitrypsin (A1AT) as a strong protease inhibitor plays a major role in the protection of tissues ..... populations over generations; iii) Different statistical models used to analyse the data. For the traits ...

  6. Intravenous alpha-1 antitrypsin augmentation therapy: systematic review

    DEFF Research Database (Denmark)

    Gøtzsche, Peter C; Johansen, Helle Krogh

    2010-01-01

    We reviewed the benefits and harms of augmentation therapy with alpha-1 antitrypsin in patients with alpha-1 antitrypsin deficiency and lung disease. We searched for randomised trials comparing augmentation therapy with placebo or no treatment in PubMed and ClinicalTrials (7 January 2010). Two...

  7. Alpha-1 Antitrypsin Deficiency

    Science.gov (United States)

    ... the Liver Galactosemia Gilbert’s Syndrome Diseases of the Liver Glycogen Storage Disease Type 1 (von Gierke) Hemochromatosis Hepatic Encephalopathy Hepatitis A Hepatitis B Hepatitis C Intrahepatic Cholestasis of Pregnancy (ICP) Jaundice In Newborns ...

  8. Alpha-1 Antitrypsin Deficiency

    Science.gov (United States)

    ... and Clinical Studies to hear experts, parents, and children talk about their experiences with clinical research. More Information Related Health Topics Cough How the Lungs Work Lung Transplant Oxygen Therapy Pulmonary Function Tests Pulmonary Rehabilitation Other Resources Non- ...

  9. Identification of a novel SERPINA-1 mutation causing alpha-1 antitrypsin deficiency in a patient with severe bronchiectasis and pulmonary embolism

    Directory of Open Access Journals (Sweden)

    Milger K

    2015-05-01

    Full Text Available Katrin Milger,1 Lesca Miriam Holdt,2 Daniel Teupser,2 Rudolf Maria Huber,1 Jürgen Behr,1 Nikolaus Kneidinger1 1Department of Internal Medicine V, University of Munich, Comprehensive Pneumology Center, Member of the German Center for Lung Research, 2Institute of Laboratory Medicine, University of Munich, Munich, Germany Abstract: Deficiency in the serine protease inhibitor, alpha-1 antitrypsin (AAT, is known to cause emphysema and liver disease. Other manifestations, including airway disease or skin disorders, have also been described. A 44-year-old woman presented to our emergency department with dyspnea and respiratory insufficiency. She had never smoked, and had been diagnosed with COPD 9 years earlier. Three months previously, she had suffered a pulmonary embolism. Chest computed tomography scan revealed severe cystic bronchiectasis with destruction of the lung parenchyma. The sweat test was normal and there was no evidence of the cystic fibrosis transmembrane conductance regulator (CFTR mutation. Capillary zone electrophoresis showed a decrease of alpha-1 globin band and AAT levels were below the quantification limit (<25 mg/dL. No S or Z mutation was identified, but sequencing analysis found a homozygous cytosine and adenine (CA insertion in exon 2 of the SERPINA-1 gene, probably leading to a dysfunctional protein (PI Null/Null. This mutation has not been previously identified. The atypical presentation of the patient, with severe cystic bronchiectasis, highlights AAT deficiency as a differential diagnosis in bronchiectasis. Further, awareness should be raised regarding a possible increased risk of thromboembolism associated with AAT deficiency. Keywords: alpha-1 antitrypsin deficiency, bronchiectasis, SERPINA-1 mutation, pulmonary embolism

  10. Clinical utility of alpha-1 proteinase inhibitor in the management of adult patients with severe alpha-1 antitrypsin deficiency: a review of the current literature

    Directory of Open Access Journals (Sweden)

    Parr DG

    2017-07-01

    Full Text Available David G Parr, Beatriz Lara Department of Respiratory Medicine, Cardio-Respiratory Division, University Hospital Coventry, Coventry, UK Abstract: Alpha-1 antitrypsin (AAT functions primarily to inhibit neutrophil elastase, and its deficiency predisposes individuals to the development of chronic obstructive pulmonary disease (COPD. The putative protective serum concentration is generally considered to be above a threshold of 11 µM/L, and therapeutic augmentation of AAT above this value is believed to retard the progression of emphysema. Several AAT preparations, all derived from human donor plasma, have been commercialized since approval by the US Food and Drug Administration (FDA in 1987. Biochemical efficacy has been demonstrated by augmentation of pulmonary antiprotease activity, but demonstration of clinical efficacy in randomized, placebo-controlled trials has been hampered by the practical difficulties of performing conventional studies in a rare disease with a relatively long natural history. Computed tomography has been applied to measure lung density as a more specific and sensitive surrogate outcome measure of emphysema than physiologic indices, such as forced expiratory volume in 1 second, and studies consistently show a therapeutic reduction in the rate of lung density decline. However, convincing evidence of benefit using traditional clinical measures remains elusive. Intravenous administration of AAT at a dose of 60 mg/kg/week is the commonest regime in use and has well-documented safety and tolerability. International and national guidelines on the management of AAT deficiency recommend intravenous augmentation therapy to supplement optimized usual COPD treatment in patients with severe deficiency and evidence of lung function impairment. Keywords: alpha-1 antitrypsin deficiency, augmentation or replacement therapy, computed tomography, emphysema, COPD

  11. Exploring the optimum approach to the use of CT densitometry in a randomised placebo-controlled study of augmentation therapy in alpha 1-antitrypsin deficiency

    DEFF Research Database (Denmark)

    Parr, David G; Dirksen, Asger; Piitulainen, Eeva

    2009-01-01

    BACKGROUND: Computed tomography (CT) lung densitometry has been demonstrated to be the most sensitive and specific outcome measure for the assessment of emphysema-modifying therapy, but the optimum densitometric index has yet to be determined and targeted sampling may be more sensitive than whole...... lung assessment. The EXAcerbations and CT scan as Lung Endpoints (EXACTLE) trial aimed to clarify the optimum approach to the use of CT densitometry data for the assessment of alpha 1-antitrypsin (AAT) augmentation therapy on the progression of emphysema in AAT deficiency (AATD). METHODS: Patients...... of emphysema in the apical, middle and basal regions of the lung by measurement with PD15 showed that this treatment effect was more evident when the basal third was sampled (1.722 g/L, p = 0.040). A comparison between different densitometric indices indicated that the influence of inspiratory variability...

  12. Intensive smoking diminishes the differences in quality of life and exacerbation frequency between the alpha-1-antitrypsin deficiency genotypes PiZZ and PiSZ.

    Science.gov (United States)

    Bernhard, Nikolas; Lepper, Philipp M; Vogelmeier, Claus; Seibert, Martina; Wagenpfeil, Stefan; Bals, Robert; Fähndrich, Sebastian

    2017-09-01

    Alpha-1-antitrypsin deficiency (AATD) is a rare genetic disorder that is associated with low levels of circulating alpha-1-antitrypsin in serum. In comparison to the genotype PiZZ, PiSZ usually leads to lower risk of emphysema, better lung function and better survival. The aim of this study was to analyze the relationship between cigarette smoking (packyears) and the AATD genotypes (PiZZ and PiSZ) concerning quality of life (SGRQ), transfer factor of the lung for carbon monoxide (TLCO), forced expiratory volume in one second (FEV 1 ) and exacerbation rate. We compared PiZZ and PiSZ individuals from the German registry for individuals with AATD (AATDR) in univariate analysis and multivariate linear regression models. All subjects were stratified into three groups according to their cumulative nicotine consumption (0 py; 0 < py < 30; ?30 py). 868 PiZZ individuals (mean age 52.6 ± 12.8 years (43.5% female)) and 114 PiSZ individuals (mean age 50.3 ± 17.4 years (46.5% female)) were compared. In contrast to never- and intensive (ex-) smokers, moderate (ex-) smoking PiSZ individuals had a significantly better SGRQ total score (B = ?8.148; p = 0.020) and less exacerbations (B = ?0.354; p = 0.037) than individuals with PiZZ in multivariate analysis. The differences in quality of life and exacerbation frequency between PiZZ and PiSZ individuals diminish by intensive (ex-) smoking. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Exacerbations and duration of smoking abstinence are associated with the annual loss of FEV1 in individuals with PiZZ alpha-1-antitrypsin deficiency.

    Science.gov (United States)

    Fähndrich, Sebastian; Bernhard, Nikolas; Lepper, Philipp M; Vogelmeier, Claus; Seibert, Martina; Wagenpfeil, Stefan; Bals, Robert

    2017-08-01

    Alpha-1-antitrypsin deficiency (AATD) is a genetic disorder that is associated with a higher risk of chronic obstructive pulmonary disease (COPD) and emphysema. The annual declines in lung function (FEV 1 ) and transfer factor of the lung for carbon monoxide (TLCO) predict all-cause mortality. We investigated the longitudinal follow-up data over 11 years (mean follow-up period of 4.89 years) from the German AATD registry and analyzed the relationship between annual loss of FEV 1 and TLCO and sex, age, body mass index (BMI), nicotine consumption, occupational dust exposure, St. George's Respiratory Questionnaire (SGRQ) score, baseline FEV 1 or TLCO, alpha-1-antitrypsin (AAT) serum level, exacerbation frequency and the duration of smoking abstinence by multiple linear generalized estimating equations models (GEE-models). We evaluated the data of 100 individuals with post-bronchodilator FEV 1 measurements and from 116 individuals with TLCO measurements. The mean overall decline was -54.06 ± 164.62 ml/year in FEV 1 and -0.17 ± 0.70 mmol/min/kPa/year in TLCO. Accelerated deterioration of FEV 1 was associated with occupational dust exposure (p = 0.026), shorter duration of smoking abstinence (p = 0.008), higher baseline FEV 1 (p = 0.003), higher annual exacerbation frequency (p = 0.003) and higher frequency of glucocorticoids intake (p = 0.004). Furthermore, patients with an elevated decline in TLCO showed significant impaired health-related quality of life at baseline (p = 0.039) and lower AAT serum levels (p < 0.001) in multivariate analysis. Annual decline in FEV 1 is related to the exacerbation rate, occupational dust exposure and the duration of smoking abstinence. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Health status and lung function in the Swedish alpha 1-antitrypsin deficient cohort, identified by neonatal screening, at the age of 37-40 years

    Directory of Open Access Journals (Sweden)

    Piitulainen E

    2017-02-01

    Full Text Available Eeva Piitulainen, Behrouz Mostafavi, Hanan A Tanash Department of Respiratory Medicine and Allergology, Skåne University Hospital, Lund University, Malmö, Sweden Background: Severe alpha 1-antitrypsin (AAT deficiency (genotype PiZZ is a well-known risk factor for COPD. A cohort of PiZZ and PiSZ individuals was identified by the Swedish national neonatal AAT screening program in 1972–1974 and followed up regularly since birth. Our aim was to study the lung function, respiratory symptoms and health status at the age of 38 years in comparison with a random sample of control subjects selected from the population registry.Methods: The study group included 120 PiZZ, 46 PiSZ and 164 control subjects (PiMM, who answered a questionnaire on smoking habits and symptoms and the Saint George Respiratory Questionnaire (SGRQ on quality of life. A total of 89 PiZZ, 33 PiSZ and 92 PiMM subjects underwent spirometry.Results: Four percent of the PiZZ, 2% of the PiSZ and 12% of the control subjects were current smokers (P=0.008, and 17% of the PiZZ, 9% of the PiSZ and 21% of the control subjects had stopped smoking. The PiZZ current smokers had a significantly higher (ie, poorer median activity score according to the SGRQ than the PiZZ never-smokers (P=0.032. The PiMM current smokers had significantly higher activity score (P<0.001, symptom score (P<0.001, and total score (P=0.001 according to the SGRQ than the PiMM never-smokers. The PiZZ current smokers had a significantly lower postbronchodilator forced expiratory volume in 1 second (FEV1% of predicted value (P=0.019 and FEV1/forced vital capacity (FVC ratio (P=0.032 than the PiZZ never-smokers. The proportion of subjects with a FEV1/FVC ratio of <0.70, indicating COPD, was significantly higher in the PiZZ current smokers than in the PiZZ never-smokers (P=0.001. Among the PiSZ and PiMM subjects, the differences in lung function between the smoking subgroups were insignificant.Conclusion: PiZZ current

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

    Directory of Open Access Journals (Sweden)

    Andrew A. Wilson

    2015-05-01

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

  16. Association of polymorphism in the alpha-1-antitrypsin gene with ...

    African Journals Online (AJOL)

    Alpha-1-antitrypsin (A1AT) as a strong protease inhibitor plays a major role in the protection of tissues against proteolytic destruction by neutrophil elastase. Existence of this protein in the mammary gland may increase the survival of milk proteins such as lactoferrin and lysozyme. The biological role of A1AT in tissues such ...

  17. Ni(ii) ions cleave and inactivate human alpha-1 antitrypsin hydrolytically, implicating nickel exposure as a contributing factor in pathologies related to antitrypsin deficiency.

    Science.gov (United States)

    Wezynfeld, Nina Ewa; Bonna, Arkadiusz; Bal, Wojciech; Frączyk, Tomasz

    2015-04-01

    Human alpha-1 antitrypsin (AAT) is an abundant serum protein present at a concentration of 1.0-1.5 g L(-1). AAT deficiency is a genetic disease that manifests with emphysema and liver cirrhosis due to the accumulation of a misfolded AAT mutant in hepatocytes. Lung AAT amount is inversely correlated with chronic obstructive pulmonary disease (COPD), a serious and often deadly condition, with increasing frequency in the aging population. Exposure to cigarette smoke and products of fossil fuel combustion aggravates AAT deficiency and COPD according to mechanisms that are not fully understood. Taking into account that these fumes contain particles that can release nickel to human airways and skin, we decided to investigate interactions of AAT with Ni(ii) ions within the paradigm of Ni(ii)-dependent peptide bond hydrolysis. We studied AAT protein derived from human blood using HPLC, SDS-PAGE, and mass spectrometry. These studies were aided by spectroscopic experiments on model peptides. As a result, we identified three hydrolysis sites in AAT. Two of them are present in the N-terminal part of the molecule next to each other (before Thr-13 and Ser-14 residues) and effectively form one N-terminal cleavage site. The single C-terminal cleavage site is located before Ser-285. The N-terminal hydrolysis was more efficient than the C-terminal one, but both abolished the ability of AAT to inhibit trypsin in an additive manner. Nickel ions bound to hydrolysis products demonstrated an ability to generate ROS. These results implicate Ni(ii) exposure as a contributing factor in AAT-related pathologies.

  18. Origins and spreads of Alpha 1 antitrypsin variants in world human ...

    African Journals Online (AJOL)

    This alpha 1 antitrypsin deficiency (AATD) represents a common hereditary disorder that mainly manifests as obstructive lung diseases and less common liver ... Anthropological history of Alpha 1 antitrypsin variants / Denden et al. ..... PIZ allele to be 2000 years or 66 generations, by analyzing STR and RFLP markers on.

  19. The impact of smoke exposure on the clinical phenotype of alpha-1 antitrypsin deficiency in Ireland: exploiting a national registry to understand a rare disease.

    Science.gov (United States)

    O'Brien, M Emmet; Pennycooke, Kevin; Carroll, Tomás P; Shum, Jonathan; Fee, Laura T; O'Connor, Catherine; Logan, P Mark; Reeves, Emer P; McElvaney, Noel G

    2015-05-01

    Individuals with Alpha-1 antitrypsin deficiency (AATD) have mutations in the SERPINA1 gene causing genetic susceptibility to early onset lung and liver disease that may result in premature death. Environmental interactions have a significant impact in determining the disease phenotype and outcome in AATD. The aim of this study was to assess the impact of smoke exposure on the clinical phenotype of AATD in Ireland. Clinical demographics and available thoracic computerised tomography (CT) imaging were detected from 139 PiZZ individuals identified from the Irish National AATD Registry. Clinical information was collected by questionnaire. Data was analysed to assess AATD disease severity and evaluate predictors of clinical phenotype. Questionnaires were collected from 107/139 (77%) and thoracic CT evaluation was available in 72/107 (67.2%). 74% of respondents had severe Chronic Obstructive Pulmonary Disease (COPD) (GOLD stage C or D). Cigarette smoking was the greatest predictor of impairment in FEV1 and DLCO (%predicted) and the extent of emphysema correlated most significantly with DLCO. Interestingly the rate of FEV1 decline was similar in ex-smokers when compared to never-smokers. Passive smoke exposure in childhood resulted in a greater total pack-year smoking history. Radiological evidence of bronchiectasis was a common finding and associated with increasing age. The Irish National AATD Registry facilitates clinical and basic science research of this condition in Ireland. This study illustrates the detrimental effect of smoke exposure on the clinical phenotype of AATD in Ireland and the benefit of immediate smoking cessation at any stage of lung disease.

  20. Active trafficking of alpha 1 antitrypsin across the lung endothelium.

    Directory of Open Access Journals (Sweden)

    Angelia D Lockett

    Full Text Available The homeostatic lung protective effects of alpha-1 antitrypsin (A1AT may require the transport of circulating proteinase inhibitor across an intact lung endothelial barrier. We hypothesized that uninjured pulmonary endothelial cells transport A1AT to lung epithelial cells. Purified human A1AT was rapidly taken up by confluent primary rat pulmonary endothelial cell monolayers, was secreted extracellularly, both apically and basolaterally, and was taken up by adjacent rat lung epithelial cells co-cultured on polarized transwells. Similarly, polarized primary human lung epithelial cells took up basolaterally-, but not apically-supplied A1AT, followed by apical secretion. Evidence of A1AT transcytosis across lung microcirculation was confirmed in vivo by two-photon intravital microscopy in mice. Time-lapse confocal microscopy indicated that A1AT co-localized with Golgi in the endothelium whilst inhibition of the classical secretory pathway with tunicamycin significantly increased intracellular retention of A1AT. However, inhibition of Golgi secretion promoted non-classical A1AT secretion, associated with microparticle release. Polymerized A1AT or A1AT supplied to endothelial cells exposed to soluble cigarette smoke extract had decreased transcytosis. These results suggest previously unappreciated pathways of A1AT bidirectional uptake and secretion from lung endothelial cells towards the alveolar epithelium and airspaces. A1AT trafficking may determine its functional bioavailablity in the lung, which could be impaired in individuals exposed to smoking or in those with A1AT deficiency.

  1. Health status and lung function in the Swedish alpha 1-antitrypsin deficient cohort, identified by neonatal screening, at the age of 37-40 years.

    Science.gov (United States)

    Piitulainen, Eeva; Mostafavi, Behrouz; Tanash, Hanan A

    2017-01-01

    Severe alpha 1-antitrypsin (AAT) deficiency (genotype PiZZ) is a well-known risk factor for COPD. A cohort of PiZZ and PiSZ individuals was identified by the Swedish national neonatal AAT screening program in 1972-1974 and followed up regularly since birth. Our aim was to study the lung function, respiratory symptoms and health status at the age of 38 years in comparison with a random sample of control subjects selected from the population registry. The study group included 120 PiZZ, 46 PiSZ and 164 control subjects (PiMM), who answered a questionnaire on smoking habits and symptoms and the Saint George Respiratory Questionnaire (SGRQ) on quality of life. A total of 89 PiZZ, 33 PiSZ and 92 PiMM subjects underwent spirometry. Four percent of the PiZZ, 2% of the PiSZ and 12% of the control subjects were current smokers ( P =0.008), and 17% of the PiZZ, 9% of the PiSZ and 21% of the control subjects had stopped smoking. The PiZZ current smokers had a significantly higher (ie, poorer) median activity score according to the SGRQ than the PiZZ never-smokers ( P =0.032). The PiMM current smokers had significantly higher activity score ( P <0.001), symptom score ( P <0.001), and total score ( P =0.001) according to the SGRQ than the PiMM never-smokers. The PiZZ current smokers had a significantly lower postbronchodilator forced expiratory volume in 1 second (FEV 1 )% of predicted value ( P =0.019) and FEV 1 /forced vital capacity (FVC) ratio ( P =0.032) than the PiZZ never-smokers. The proportion of subjects with a FEV 1 /FVC ratio of <0.70, indicating COPD, was significantly higher in the PiZZ current smokers than in the PiZZ never-smokers ( P =0.001). Among the PiSZ and PiMM subjects, the differences in lung function between the smoking subgroups were insignificant. PiZZ current smokers were found to have signs of COPD before 40 years of age. Smoking is less common among the AAT-deficient subjects identified by neonatal screening than among their peers in the general

  2. Bioequivalence of a Liquid Formulation of Alpha1-Proteinase Inhibitor Compared with Prolastin®-C (Lyophilized Alpha1-PI) in Alpha1-Antitrypsin Deficiency.

    Science.gov (United States)

    Barker, Alan F; Campos, Michael A; Brantly, Mark L; Stocks, James M; Sandhaus, Robert A; Lee, Douglas; Steinmann, Kimberly; Lin, Jiang; Sorrells, Susan

    2017-12-01

    This study evaluated the bioequivalence, safety, and immunogenicity of a new liquid formulation of human plasma-derived alpha 1 -proteinase inhibitor, Liquid Alpha 1 -PI, compared with the Lyophilized Alpha 1 -PI formulation (Prolastin®-C), for augmentation therapy in patients with alpha 1 -antitrypsin deficiency (AATD). In this double-blind, randomized, 20-week crossover study, 32 subjects with AATD were randomized to receive 8 weekly infusions of 60 mg/kg of Liquid Alpha 1 -PI or Lyophilized Alpha 1 -PI. Serial blood samples were drawn for 7 days after the last dose followed by 8 weeks of the alternative treatment. The primary endpoint was bioequivalence at steady state, as measured by area under the concentration versus time curve from 0 to 7 days (AUC 0-7 days ) postdose using an antigenic content assay. Bioequivalence was defined as 90% confidence interval (CI) for the ratio of the geometric least squares (LS) mean of AUC 0-7 days for both products within the limits of 0.80 and 1.25. Safety and immunogenicity were assessed. Mean alpha 1 -PI concentration versus time curves for both formulations were superimposable. Mean AUC 0-7 days was 20 320 versus 19 838 mg × h/dl for Liquid Alpha 1 -PI and Lyophilized Alpha 1 -PI, respectively. The LS mean ratio of AUC 0-7 days (90% CI) for Liquid Alpha 1 -PI versus Lyophilized Alpha 1 -PI was 1.05 (1.03-1.08), indicating bioequivalence. Liquid Alpha 1 -PI was well tolerated and adverse events were consistent with Lyophilized Alpha 1 -PI. Immunogenicity to either product was not detected. In conclusion, Liquid Alpha 1 -PI is bioequivalent to Lyophilized Alpha 1 -PI, with a similar safety profile. The liquid formulation would eliminate the need for reconstitution and shorten preparation time for patients receiving augmentation therapy for AATD.

  3. Change in lung function and morbidity from chronic obstructive pulmonary disease in alpha1-antitrypsin MZ heterozygotes

    DEFF Research Database (Denmark)

    Dahl, Morten; Tybjaerg-Hansen, Anne; Lange, Peter

    2002-01-01

    A deteriorating effect of severe alpha(1)-antitrypsin deficiency (ZZ genotype) on lung function is well known, whereas the role of intermediate deficiency (MZ genotype) remains uncertain.......A deteriorating effect of severe alpha(1)-antitrypsin deficiency (ZZ genotype) on lung function is well known, whereas the role of intermediate deficiency (MZ genotype) remains uncertain....

  4. Chronic obstructive pulmonary disease in alpha1-antitrypsin PI MZ heterozygotes

    DEFF Research Database (Denmark)

    Hersh, C P; Dahl, Morten; Ly, N P

    2004-01-01

    Severe alpha(1)-antitrypsin deficiency, usually related to homozygosity for the protease inhibitor (PI) Z allele, is a proven genetic risk factor for chronic obstructive pulmonary disease (COPD). The risk of COPD in PI MZ heterozygous individuals is controversial.......Severe alpha(1)-antitrypsin deficiency, usually related to homozygosity for the protease inhibitor (PI) Z allele, is a proven genetic risk factor for chronic obstructive pulmonary disease (COPD). The risk of COPD in PI MZ heterozygous individuals is controversial....

  5. Alpha-1-antitrypsin is produced by human neutrophil granulocytes and their precursors and liberated during granule exocytosis

    DEFF Research Database (Denmark)

    Clemmensen, Stine N; Jacobsen, Lars C; Rørvig, Sara

    2011-01-01

    Alpha-1-antitrypsin (A1AT) is an important inhibitor of neutrophil proteases including elastase, cathepsin G, and proteinase 3. Transcription profiling data suggest that A1AT is expressed by human neutrophil granulocytes during all developmental stages. A1AT has hitherto only been found associated....... Neutrophils from patients with A1AT-deficiency carrying the (PI)ZZ mutation in the A1AT gene appeared structurally and functionally normal, but A1AT produced in leukocytes of these patients lacked the ability to bind proteases efficiently. We conclude that A1AT generation and release from neutrophils add...

  6. Learning about Alpha-1 Antitrypsin Deficiency (AATD)

    Science.gov (United States)

    ... weight loss. Some Individuals with AATD have advanced lung disease and have emphysema, in which the small air sacs (alveoli) in the lungs are damaged. Symptoms of emphysema include difficulty breathing, ...

  7. Genetics Home Reference: alpha-1 antitrypsin deficiency

    Science.gov (United States)

    ... rapid heartbeat upon standing. Affected individuals often develop emphysema, which is a lung disease caused by damage to the small air ... exposure to tobacco smoke accelerates the appearance of emphysema symptoms and damage to the lungs. About 10 percent of infants with alpha-1 ...

  8. Fibrinogen and alpha(1)-antitrypsin in COPD exacerbations

    DEFF Research Database (Denmark)

    Sylvan Ingebrigtsen, Truls; Marott, J. L.; Rode, L.

    2015-01-01

    Background We tested the hypotheses that fibrinogen and alpha(1)-antitrypsin are observationally and genetically associated with exacerbations in COPD. Methods We studied 13 591 individuals with COPD from the Copenhagen General Population Study (2003-2013), of whom 6857 were genotyped for FGB -455...... and exacerbations in instrumental variable analyses. Results Elevated fibrinogen and alpha(1)-antitrypsin levels were associated with increased risk of exacerbations in COPD, HR=1.14 (1.07 to 1.22, p...

  9. Hepatic-targeted RNA interference provides persistent knockdown of alpha-1 antitrypsin levels in ZZ patients.

    Science.gov (United States)

    Turner, Alice M; Stolk, Jan; Bals, Robert; Lickliter, Jason; Hamilton, James; Christianson, Dawn R; Given, Bruce D; Burdon, Jonathan G; Loomba, Rohit; Stoller, James K; Teckman, Jeffery H

    2018-03-20

    Alpha-1 antitrypsin deficiency (AATD) is a genetic disorder causing pulmonary and liver disease. The PiZ mutation results in mis-folded alpha-1 antitrypsin protein (Z-AAT) leading to hepatocyte accumulation, fibrosis and cirrhosis. RNAi-based therapeutics silencing production of hepatic Z-AAT might benefit patients with AATD-associated liver disease. This study evaluated an RNAi therapeutic to silence production of alpha-1 antitrypsin. Part A of this double-blind first-in-human study randomized 54 healthy volunteers (HVs) into single dose cohorts (2 placebo: 4 active), receiving escalating doses of the investigational agent ARC-AAT from 0.38 to 8.0 mg/kg or placebo. Part B randomized 11 PiZZ genotype AATD patients who received up to 4.0 mg/kg or placebo. Patients with baseline FibroScan® >11 kPa or FEV 1 (forced expiratory volume in one second) < 60% were excluded. Assessments included safety, pharmacokinetics, and change in serum alpha-1 antitrypsin (AAT) concentrations. 36 healthy volunteers received ARC-AAT and 18 received placebo (Part A). Seven PiZZ individuals received ARC-AAT and 4 received placebo (Part B). A dose-response in serum AAT reduction was observed at doses ≥ 4 mg/kg with similar relative reductions in PiZZ patients and HVs at 4 mg/kg and a maximum reduction of 76.1% (HVs) vs. 78.8% (PiZZ) at this dose. Time for serum AAT return to baseline was similar for HV and PiZZ. There were no notable differences between HV and PiZZ safety parameters. The study was terminated early due to toxicity findings related to the delivery vehicle (ARC-EX1) seen in a non-human primate study. PiZZ and HV responded similarly to ARC-AAT. Deep and durable knockdown of hepatic AAT production based on observed reduction in serum AAT concentrations was demonstrated. Accumulation of abnormal proteins in the livers of patients with alpha-1 antitrypsin deficiency may lead to decreased liver function and potentially liver failure. Therapeutics targeting the production of

  10. Alpha-1-antitrypsin studies: canine serum and canine surfactant protein

    International Nuclear Information System (INIS)

    Tuttle, W.C.; Slauson, D.O.; Dahlstrom, M.; Gorman, C.

    1974-01-01

    Canine serum alpha-1-antitrypsin was isolated by gel filtration and affinity chromatography and characterized by polyacrylamide gel electrophoresis and immunoelectrophoresis. Measurement of the trypsin inhibitory capacity of the separated protein indicated a ninefold concentration of functional trypsin inhibitor during the isolation procedure. Electrophoresis demonstrated the presence of a single protein with alpha-globulin mobility and a molecular weight near that of human alpha-1-antitrypsin. The trypsin inhibitory capacity of pulmonary surfactant protein from five Beagle dogs was measured, related to total surfactant protein concentration, and compared with similar measurements on whole serum from the same animals. Results indicated a variable concentration of trypsin inhibitor in the canine pulmonary surfactant protein. However, the concentration in the surfactant protein was always significantly higher than that in the corresponding serum sample. Preliminary experiments designed to separate the trypsin inhibitory fraction(s) from the other surfactant proteins by gel filtration chromatography indicated that the trypsin inhibitor was probably a single protein with a molecular weight near that of alpha-1-antitrypsin. (U.S.)

  11. Quantification of Total Human Alpha-1 Antitrypsin by Sandwich ELISA.

    Science.gov (United States)

    Tang, Qiushi; Gruntman, Alisha M; Flotte, Terence R

    2017-01-01

    In this chapter we describe an enzyme-linked immunosorbent assay (ELISA) to quantitatively measure human alpha-1 antitrypsin (AAT) protein levels in serum, other body fluids or liquid media. This assay can be used to measure the expression of the human AAT (hAAT) gene in a variety of gene transfer or gene downregulation experiments.A hAAT-specific capture antibody and a HRP-conjugated anti-AAT detection antibody are used in this assay. The conjugated anti-AAT used in this protocol, instead of the typical sandwich which employs an unconjugated antibody followed by a specifically conjugated IgG, makes the assay simpler and decreases variability. This provides a useful tool to evaluate the AAT levels in clinical and research samples and can allow fairly rapid testing of a large number of samples.

  12. Alpha-1 antitrypsin Pi*SZ genotype: estimated prevalence and number of SZ subjects worldwide

    Directory of Open Access Journals (Sweden)

    Blanco I

    2017-06-01

    Full Text Available Ignacio Blanco,1 Patricia Bueno,2 Isidro Diego,3 Sergio Pérez-Holanda,4 Beatriz Lara,5 Francisco Casas-Maldonado,6 Cristina Esquinas,7 Marc Miravitlles7,8 1Alpha1-Antitrypsin Deficiency Spanish Registry (REDAAT, Lung Foundation Breathe, Spanish Society of Pneumology (SEPAR, Barcelona, Spain; 2Internal Medicine Department, County Hospital of Jarrio, Principality of Asturias, Spain; 3Materials and Energy Department, School of Mining Engineering, Oviedo University, Principality of Asturias, Spain; 4Surgical Department, University Central Hospital of Asturias, Oviedo, Spain; 5Respiratory Medicine Department, Coventry and Warwickshire University Hospital, Coventry, UK; 6Pneumology Department, University Hospital San Cecilio, Granada, Spain; 7Pneumology Department, Hospital Universitari Vall d’Hebron, Barcelona, Spain; 8CIBER de Enfermedades Respiratorias (CIBERES, Barcelona, Spain Abstract: The alpha-1 antitrypsin (AAT haplotype Pi*S, when inherited along with the Pi*Z haplotype to form a Pi*SZ genotype, can be associated with pulmonary emphysema in regular smokers, and less frequently with liver disease, panniculitis, and systemic vasculitis in a small percentage of people, but this connection is less well established. Since the detection of cases can allow the application of preventive measures in patients and relatives with this congenital disorder, the objective of this study was to update the prevalence of the SZ genotype to achieve accurate estimates of the number of Pi*SZ subjects worldwide, based on studies performed according to the following criteria: 1 samples representative of the general population, 2 AAT phenotyping characterized by adequate methods, and 3 selection of studies with reliable results assessed with a coefficient of variation calculated from the sample size and 95% confidence intervals. Studies fulfilling these criteria were used to develop tables and maps with an inverse distance-weighted (IDW interpolation method, to

  13. Environmental arsenic exposure, selenium and sputum alpha-1 antitrypsin

    DEFF Research Database (Denmark)

    Burgess, Jefferey L; Kurzius-Spencer, Margaret; Poplin, Gerald S

    2014-01-01

    Exposure to arsenic in drinking water is associated with increased respiratory disease. Alpha-1 antitrypsin (AAT) protects the lung against tissue destruction. The objective of this study was to determine whether arsenic exposure is associated with changes in airway AAT concentration and whether...... this relationship is modified by selenium. A total of 55 subjects were evaluated in Ajo and Tucson, Arizona. Tap water and first morning void urine were analyzed for arsenic species, induced sputum for AAT and toenails for selenium and arsenic. Household tap-water arsenic, toenail arsenic and urinary inorganic...... arsenic and metabolites were significantly higher in Ajo (20.6±3.5 μg/l, 0.54±0.77 μg/g and 27.7±21.2 μg/l, respectively) than in Tucson (3.9±2.5 μg/l, 0.16±0.20 μg/g and 13.0±13.8 μg/l, respectively). In multivariable models, urinary monomethylarsonic acid (MMA) was negatively, and toenail selenium...

  14. Alpha-1 antitrypsin is a potential biomarker for hepatitis B

    Directory of Open Access Journals (Sweden)

    Chen Zhi

    2011-06-01

    Full Text Available Abstract Background Function exertion of specific proteins are key factors in disease progression, thus the systematical identification of those specific proteins is a prerequisite to understand various diseases. Though many proteins have been verified to impact on hepatitis, no systematical protein screening has been documented to hepatitis B virus (HBV induced hepatitis, hindering the comprehensive understanding to this severe disease. Aim To identify the major proteins in the progression of HBV infection from mild stage to severe stage. Methods We performed an integrated strategy by combining two-dimensional electrophoresis (2-DE, peptide mass fingerprinting (PMF analysis, and tissue microarray techniques to screen the functional proteins and detect the localization of those proteins. Results Interestingly, MS/MS identification revealed the expression level of alpha-1 antitrypsin (AAT was significantly elevated in serum samples from patients with severe chronic hepatitis. Immunoblotting with a specific AAT antibody confirmed that AAT is highly expressed in serum samples from patients with hepatic carcinoma and severe chronic hepatitis. Furthermore, we observed that AAT is with highest expression in normal tissue and cells, but lowest in hepatic carcinoma and severe chronic hepatitis tissues and cells, suggesting the specific secretion of AAT from tissues and cells to serum. Conclusion These results suggest the possibility of AAT as a potential biomarker for hepatitis B in diagnosis.

  15. Endothelial alpha-1-antitrypsin attenuates cigarette smoke induced apoptosis in vitro.

    Science.gov (United States)

    Aldonyte, Ruta; Hutchinson, Tarun Edgar; Hutchinson, Edgar Tarun; Jin, Bilian; Brantly, Mark; Block, Edward; Patel, Jawaharlal; Zhang, Jianliang

    2008-06-01

    Deficiency of the antiprotease alpha-1-antitrypsin (AAT) and exposure to cigarette smoke (CS) contribute to the development of early onset emphysema. CS-induced apoptosis of alveolar cells including endothelial cells plays critical role in the lung destruction. AAT deficiency is associated with increased lung tissue destruction as well. We hypothesize that AAT protects lung alveoli from noxious environmental stimuli such as CS-induced apoptosis. Porcine pulmonary artery endothelial cells (PAEC) were exposed to CS in the presence or absence of AAT (20 microM). AAT internalization and markers for apoptosis were assessed by confocal microscopy. Flow cytometry was performed in parallel to quantify the number of AAT-loaded and apoptotic cells. We demonstrated that exogenous AAT accumulated in PAEC and protected cells from CS-induced apoptosis. AAT-loaded CS-exposed cells exhibited increased amounts of chaperone HSP-70 in their cytosol and less apoptosis inducing factor in their nuclei compared to AAT-untreated, CS-exposed cells. Our results suggest that AAT is taken up by endothelial cells via two mechanisms and that intracellular AAT may have a protective role in CS-induced endothelial apoptosis. This may open new insights into the field of endothelial serpins as agents capable of protecting the vasculature from environment-derived noxious substances.

  16. SVIP regulates Z variant alpha-1 antitrypsin retro-translocation by inhibiting ubiquitin ligase gp78.

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    Nazli Khodayari

    Full Text Available Alpha-1 antitrypsin deficiency (AATD is an inherited disorder characterized by early-onset emphysema and liver disease. The most common disease-causing mutation is a single amino acid substitution (Glu/Lys at amino acid 342 of the mature protein, resulting in disruption of the 290-342 salt bridge (an electrophoretic abnormality defining the mutation [Z allele, or ZAAT], protein misfolding, polymerization, and accumulation in the endoplasmic reticulum of hepatocytes and monocytes. The Z allele causes a toxic gain of function, and the E3 ubiquitin ligase gp78 promotes degradation and increased solubility of endogenous ZAAT. We hypothesized that the accumulation of ZAAT is influenced by modulation of gp78 E3 ligase and SVIP (small VCP-interacting protein interaction with p97/VCP in ZAAT-expressing hepatocytes. We showed that the SVIP inhibitory effect on ERAD due to overexpression causes the accumulation of ZAAT in a human Z hepatocyte-like cell line (AT01. Overexpression of gp78, as well as SVIP suppression, induces gp78-VCP/p97 interaction in AT01 cells. This interaction leads to retro-translocation of ZAAT and reduction of the SVIP inhibitory role in ERAD. In this context, overexpression of gp78 or SVIP suppression may eliminate the toxic gain of function associated with polymerization of ZAAT, thus providing a potential new therapeutic approach to the treatment of AATD.

  17. Circulating alpha1-antitrypsin in the general population: Determinants and association with lung function

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    Berger Wolfgang

    2008-04-01

    Full Text Available Abstract Background Severe alpha1-antitrypsin (AAT deficiency associated with low AAT blood concentrations is an established genetic COPD risk factor. Less is known about the respiratory health impact of variation in AAT serum concentrations in the general population. We cross-sectionally investigated correlates of circulating AAT concentrations and its association with FEV1. Methods In 5187 adults (2669 females with high-sensitive c-reactive protein (CRP levels ≤ 10 mg/l from the population-based Swiss SAPALDIA cohort, blood was collected at the time of follow-up examination for measuring serum AAT and CRP. Results Female gender, hormone intake, systolic blood pressure, age in men and in postmenopausal women, as well as active and passive smoking were positively, whereas alcohol intake and BMI inversely correlated with serum AAT levels, independent of CRP adjustment. We observed an inverse association of AAT with FEV1 in the total study population (p Conclusion The results of this population-based study reflect a complex interrelationship between tobacco exposure, gender related factors, circulating AAT, systemic inflammatory status and lung function.

  18. Anti-apoptotic effects of Z alpha1-antitrypsin in human bronchial epithelial cells.

    LENUS (Irish Health Repository)

    Greene, C M

    2010-05-01

    alpha(1)-antitrypsin (alpha(1)-AT) deficiency is a genetic disease which manifests as early-onset emphysema or liver disease. Although the majority of alpha(1)-AT is produced by the liver, it is also produced by bronchial epithelial cells, amongst others, in the lung. Herein, we investigate the effects of mutant Z alpha(1)-AT (ZAAT) expression on apoptosis in a human bronchial epithelial cell line (16HBE14o-) and delineate the mechanisms involved. Control, M variant alpha(1)-AT (MAAT)- or ZAAT-expressing cells were assessed for apoptosis, caspase-3 activity, cell viability, phosphorylation of Bad, nuclear factor (NF)-kappaB activation and induced expression of a selection of pro- and anti-apoptotic genes. Expression of ZAAT in 16HBE14o- cells, like MAAT, inhibited basal and agonist-induced apoptosis. ZAAT expression also inhibited caspase-3 activity by 57% compared with control cells (p = 0.05) and was a more potent inhibitor than MAAT. Whilst ZAAT had no effect on the activity of Bad, its expression activated NF-kappaB-dependent gene expression above control or MAAT-expressing cells. In 16HBE14o- cells but not HEK293 cells, ZAAT upregulated expression of cIAP-1, an upstream regulator of NF-kappaB. cIAP1 expression was increased in ZAAT versus MAAT bronchial biopsies. The data suggest a novel mechanism by which ZAAT may promote human bronchial epithelial cell survival.

  19. Alpha-1 antitrypsin reduces ovariectomy-induced bone loss in mice

    Science.gov (United States)

    Alpha-1antitrypsin (AAT) is a multifunctional protein with proteinase inhibitor and anti-inflammatory activities. Recent studies showed that AAT has therapeutic effect for diseases associated with inflammation, such as type 1 diabetes and arthritis. Proinflammatory cytokines are primary mediators of...

  20. Alpha-1-antitrypsin is an endogenous inhibitor of proinflammatory cytokine production in whole blood.

    Science.gov (United States)

    Pott, Gregory B; Chan, Edward D; Dinarello, Charles A; Shapiro, Leland

    2009-05-01

    Several observations suggest endogenous suppressors of inflammatory mediators are present in human blood. alpha-1-Antitrypsin (AAT) is the most abundant serine protease inhibitor in blood, and AAT possesses anti-inflammatory activity in vitro and in vivo. Here, we show that in vitro stimulation of whole blood from persons with a genetic AAT deficiency resulted in enhanced cytokine production compared with blood from healthy subjects. Using whole blood from healthy subjects, dilution of blood with RPMI tissue-culture medium, followed by incubation for 18 h, increased spontaneous production of IL-8, TNF-alpha, IL-1 beta, and IL-1R antagonist (IL-1Ra) significantly, compared with undiluted blood. Dilution-induced cytokine production suggested the presence of one or more circulating inhibitors of cytokine synthesis present in blood. Serially diluting blood with tissue-culture medium in the presence of cytokine stimulation with heat-killed Staphylococcus epidermidis (S. epi) resulted in 1.2- to 55-fold increases in cytokine production compared with S. epi stimulation alone. Diluting blood with autologous plasma did not increase the production of IL-8, TNF-alpha, IL-1 beta, or IL-1Ra, suggesting that the endogenous, inhibitory activity of blood resided in plasma. In whole blood, diluted and stimulated with S. epi, exogenous AAT inhibited IL-8, IL-6, TNF-alpha, and IL-1 beta significantly but did not suppress induction of the anti-inflammatory cytokines IL-1Ra and IL-10. These ex vivo and in vitro observations suggest that endogenous AAT in blood contributes to the suppression of proinflammatory cytokine synthesis.

  1. Augmentation therapy with alpha1-antitrypsin: patterns of use and adverse events.

    Science.gov (United States)

    Stoller, James K; Fallat, Robert; Schluchter, Mark D; O'Brien, Ralph G; Connor, Jason T; Gross, Nicholas; O'Neil, Kevin; Sandhaus, Robert; Crystal, Ronald G

    2003-05-01

    To describe patterns of prescribing augmentation therapy, and types and rates of adverse events in the National Heart, Lung, and Blood Institute Registry for Individuals with Severe Deficiency of Alpha(1)-Antitrypsin. Observational cohort study with follow-up visits every 6 to 12 months for up to 7 years. The rate and dosing frequency with which Registry participants were prescribed to receive augmentation therapy by their managing physicians, and the type and frequency of adverse events, classified in two ways: severity of self-reported symptoms, and actions taken as a consequence of the symptom. Over the course of Registry follow-up, 66% (n = 747) of the participants received augmentation therapy at some time. In keeping with recommendations made in the 1989 American Thoracic Society (ATS) statement, 75% of participants with airflow obstruction at first visit (defined as FEV(1) or = 80% predicted (14%) also received augmentation therapy. Among those with COPD for whom augmentation therapy was not prescribed, financial constraints were the reported cause in 30%. Observed patterns also varied from approved practice, in that dosing frequencies other than the US Food and Drug Administration-approved, once-weekly regimen were frequently prescribed. The overall rate of reported adverse events was 0.02 per patient-month, with 83% of participants reporting no events. This overall rate was composed of 16% considered mild events, 76% moderate events, and 9% severe events. We conclude that augmentation therapy was generally well tolerated and, consistent with ATS guidelines, physicians generally did not prescribe augmentation therapy for subjects with FEV(1) > or = 80% predicted. However, the large percentage of subjects with FEV(1) <80% predicted not receiving augmentation therapy and the frequent use of 2- to 3-week or monthly dosing reflects variation of practice from suggested treatment guidelines.

  2. Alpha-1 antitrypsin is elevated in exhaled breath condensate and serum in exacerbated COPD patients.

    Science.gov (United States)

    Koczulla, A Rembert; Noeske, Sarah; Herr, Christian; Koepke, Janine; Jörres, Rudolf A; Nell, Christoph; Schmid, Severin; Vogelmeier, Claus; Bals, Robert

    2012-01-01

    Exacerbations of chronic obstructive pulmonary disease (COPD) significantly contribute to COPD-related morbidity. Diagnosis of COPD exacerbations may be improved by analyzing biomarkers such as alpha-1 antitrypsin (AAT). AAT is an acute-phase protein and inhibitor of neutrophil elastase. Deficiency of AAT may result in early-onset respiratory symptoms. Measurement of exhaled breath condensate (EBC) is a noninvasive method to investigate biomarkers present in the epithelial lining fluid, such as AAT. To investigate whether AAT can be detected and quantified in EBC and to compare AAT levels in the EBC of healthy controls, patients with COPD, and during exacerbations of COPD. EBC from 10 healthy controls, 17 subjects with COPD, and 18 subjects with exacerbations of COPD was collected with the RTube™ device. AAT from EBC and serum were quantified by ELISA. AAT in EBC was detectable in every individual. Patients with exacerbations of COPD had significantly increased AAT values (mean, 514.33 pg/mL, [SD 279.41 ]) compared with healthy controls (mean, 251.32 pg/mL, [SD 44.71]) and stable COPD patients (mean, 242.01 pg/mL [SD 65.74]) (P=0.0003; P=0.00003). EBC AAT showed only a correlation trend with serum AAT (r=0.3, P=0.054). AAT in EBC was detectable and quantifiable. AAT measured in EBC was significantly increased during exacerbations of COPD and can potentially be used as a biomarker in exacerbations. Copyright © 2011 Elsevier Ltd. All rights reserved.

  3. Muramidase, alpha-1 antitrypsin, alpha-1 antichymotrypsin, and S-100 protein immunoreactivity in giant cell lesions.

    Science.gov (United States)

    Regezi, J A; Zarbo, R J; Lloyd, R V

    1987-01-01

    A spectrum of giant cell lesions was evaluated for muramidase, alpha-1 antitrypsin, alpha-1 antichymotrypsin, and S-100 protein immunoreactivity using an avidin-biotin-complex immunoperoxidase method. Peripheral giant cell granuloma, central giant cell granuloma, giant cell tumor, osteitis fibrosa cystica, cherubism, and giant cell tumor of tendon sheath showed similar patterns of reactivity. Granulomatous inflammatory lesions stained more intensely for muramidase than did noninflammatory lesions. Alpha-1-antichymotrypsin was a slightly better marker of giant cell lesions than was alpha-1-antitrypsin. Positive S-100 protein staining in half the lesions was thought to be due to the presence of Langerhans cells. The results supported the belief that giant cell lesions of bone and tendon sheath are differentiated toward cells of the mononuclear-phagocyte system and that multinucleated giant cells are derived from macrophages.

  4. Recombinant AAV serotype and capsid mutant comparison for pulmonary gene transfer of alpha-1-antitrypsin using invasive and noninvasive delivery.

    Science.gov (United States)

    Liqun Wang, Rejean; McLaughlin, Thomas; Cossette, Travis; Tang, Qiushi; Foust, Kevin; Campbell-Thompson, Martha; Martino, Ashley; Cruz, Pedro; Loiler, Scott; Mueller, Christian; Flotte, Terence R

    2009-01-01

    Recombinant adeno-associated viral (rAAV) vectors have been widely used in pulmonary gene therapy research. In this study, we evaluated the transduction and expression efficiencies of several AAV serotypes and AAV2 capsid mutants with specific pulmonary targeting ligands in the mouse lung. The noninvasive intranasal delivery was compared with the traditional intratracheal lung delivery. The rAAV8 was the most efficient serotype at expressing alpha-1-antitrypsin (AAT) in the lung among all the tested serotypes and mutants. A dose of 1 x 10(10) vg of rAAV8-CB-AAT transduced a high percentage of cells in the lung when delivered intratrachealy. The serum and the broncho-alveolar lavage fluid (BALF) levels of human AAT (hAAT) were about 6- and 2.5-fold higher, respectively, than those of rAAV5 group. Among the rAAV2 capsid mutants, the rAAV2 capsid mutants that display a peptide sequence from hAAT ("long serpin") indicated a twofold increase in transgene expression. For most vectors, the serum hAAT levels achieved after intranasal delivery were 1/2 to 1/3 of those with the intratracheal method. Overall, rAAV8 was the most promising vector for the future application in gene therapy of pulmonary diseases such as AAT deficiency-related emphysema.

  5. Synthetic Cannabinoid Abuse and a Rare Alpha-1-Antitrypsin Mutant Causing Acute Fulminant Hepatitis: A Case Report and Review of the Literature

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    Kurt J. Knowles

    2017-01-01

    Full Text Available Synthetic cannabinoids (SCs abuse is on the rise because they are easily obtained over the counter; they are potent psychoactive compounds and routine drug testing does not detect them. As their abuse is on the rise, so are their detrimental side effects; however, the occurrence of acute hepatitis due to SCs abuse has been reported only once before. In this case, testing revealed that the patient was also heterozygous for alpha-1-antitrypsin (A-1-AT with the phenotype of PI⁎EM. This mutant phenotype has never been reported as a cause of A-1-AT disease and the abuse of SCs in a patient with this phenotype has also never been reported. This case illustrates the possible need to expand routine drug testing for SCs and consider A-1-AT phenotyping in certain clinical scenarios.

  6. Alpha-1 antitrypsin: a potent anti-inflammatory and potential novel therapeutic agent.

    LENUS (Irish Health Repository)

    Bergin, David A

    2012-04-01

    Alpha-1 antitrypsin (AAT) has long been thought of as an important anti-protease in the lung where it is known to decrease the destructive effects of major proteases such as neutrophil elastase. In recent years, the perception of this protein in this simple one dimensional capacity as an anti-protease has evolved and it is now recognised that AAT has significant anti-inflammatory properties affecting a wide range of inflammatory cells, leading to its potential therapeutic use in a number of important diseases. This present review aims to discuss the described anti-inflammatory actions of AAT in modulating key immune cell functions, delineate known signalling pathways and specifically to identify the models of disease in which AAT has been shown to be effective as a therapy.

  7. Causal and Synthetic Associations of Variants in the SERPINA Gene Cluster with Alpha1-antitrypsin Serum Levels

    DEFF Research Database (Denmark)

    Thun, Gian Andri; Imboden, Medea; Ferrarotti, Ilaria

    2013-01-01

    Several infrequent genetic polymorphisms in the SERPINA1 gene are known to substantially reduce concentration of alpha1-antitrypsin (AAT) in the blood. Since low AAT serum levels fail to protect pulmonary tissue from enzymatic degradation, these polymorphisms also increase the risk for early onse...

  8. Inhibition of activated protein C by recombinant alpha 1-antitrypsin variants with substitution of arginine or leucine for methionine358

    NARCIS (Netherlands)

    Heeb, M.J.; Bischoff, Rainer; Courtney, M.; Griffin, J.H.

    1990-01-01

    alpha 1-Antitrypsin (alpha 1-AT) was recently identified as a major physiologic plasma inhibitor of activated protein C. The reaction with activated protein C of recombinant alpha 1-AT containing amino acid substitutions at the reactive center was studied. The substitution of Arg358 for Met, as

  9. alpha-1-Antitrypsin (AAT)-modified donor cells suppress GVHD but enhance the GVL effect: a role for mitochondrial bioenergetics

    NARCIS (Netherlands)

    Marcondes, A.M.; Karoopongse, E.; Lesnikova, M.; Margineantu, D.; Welte, T.; Dinarello, C.A.; Hockenbery, D.; Janciauskiene, S.; Deeg, H.J.

    2014-01-01

    Hematopoietic cell transplantation is curative in many patients. However, graft-versus-host disease (GVHD), triggered by alloreactive donor cells, has remained a major complication. Here, we show an inverse correlation between plasma alpha-1-antitrypsin (AAT) levels in human donors and the

  10. Alpha-1 antitrypsin and granulocyte colony-stimulating factor as serum biomarkers of disease severity in ulcerative colitis

    DEFF Research Database (Denmark)

    Soendergaard, Christoffer; Nielsen, Ole Haagen; Seidelin, Jakob Benedict

    2015-01-01

    -stimulating factor produced a predictive model with an AUC of 0.72 when differentiating mild and moderate UC, and an AUC of 0.96 when differentiating moderate and severe UC, the latter being as reliable as CRP. CONCLUSIONS: Alpha-1 antitrypsin is identified as a potential serum biomarker of mild-to-moderate disease...

  11. Sustained secretion of human alpha-1-antitrypsin from murine muscle transduced with adeno-associated virus vectors

    Science.gov (United States)

    Song, Sihong; Morgan, Michael; Ellis, Tamir; Poirier, Amy; Chesnut, Kye; Wang, Jianming; Brantly, Mark; Muzyczka, Nicholas; Byrne, Barry J.; Atkinson, Mark; Flotte, Terence R.

    1998-01-01

    Recombinant adeno-associated virus (AAV) vectors have been used to transduce murine skeletal muscle as a platform for secretion of therapeutic proteins. The utility of this approach for treating alpha-1-antitrypsin (AAT) deficiency was tested in murine myocytes in vitro and in vivo. AAV vectors expressing the human AAT gene from either the cytomegalovirus (CMV) promoter (AAV-C-AT) or the human elongation factor 1-α promoter (AAV-E-AT) were examined. In vitro in C2C12 murine myoblasts, the expression levels in transient transfections were similar between the two vectors. One month after transduction, however, the human elongation factor 1 promoter mediated 10-fold higher stable human AAT expression than the CMV promoter. In vivo transduction was performed by injecting doses of up to 1.4 × 1013 particles into skeletal muscles of several mouse strains (C57BL/6, BALB/c, and SCID). In vivo, the CMV vector mediated higher levels of expression, with sustained serum levels over 800 μg/ml in SCID and over 400 μg/ml in C57BL/6 mice. These serum concentrations are 100,000-fold higher than those previously observed with AAV vectors in muscle and are at levels which would be therapeutic if achieved in humans. High level expression was delayed for several weeks but was sustained for over 15 wk. Immune responses were dependent upon the mouse strain and the vector dosage. These data suggest that recombinant AAV vector transduction of skeletal muscle could provide a means for replacing AAT or other essential serum proteins but that immune responses may be elicited under certain conditions. PMID:9826709

  12. Tumor necrosis factor alpha and alpha-1 antitrypsin gene variants in Serbian pediatric arterial ischemic stroke patients

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    Đorđević Valentina

    2013-01-01

    Full Text Available The etiology of arterial ischemic stroke (AIS in children is complex, and different from that in adults. Although rare, stroke in children is an important cause of mortality and morbidity. There is increasing evidence that genetic factors, including inflammation mediators, have a role in occurrence and outcome of stroke. We have chosen to assess the role of polymorphism -308G/A in the promoter of tumor necrosis factor α (TNFα gene and S and Z mutations in alpha 1-antitrypsin (AAT gene in the etiology of stroke in children. TNFα polymorphism affects plasma levels of this proinflamatory cytokine, and this could contribute to stroke pathology. It has been shown that increased AAT concentration may present a risk for AIS in children. Since S and Z mutations in AAT gene reduce its levels in plasma they could have a protective role in pediatric stroke. In this study twenty six children with AIS and 100 unrelated individuals from Serbian general population were investigated by PCR/RFLP for these gene variations. No statistically significant difference was observed between patients and general population in distribution of genotypes for -308G/A TNFα polymorphism, so its contributory role in the etiology of stroke was not evident in our group of patients. None of the tested AAT gene mutations were found in patients, which is in concordance with the proposed protective role of deficient AAT variants. AIS is a multifactorial disease, with many genes having a modest role in its pathophysiology, so further analyses of their combined effect are needed to elucidate genetic risk factors in the etiology and outcome of stroke in pediatric patients.

  13. Culture of Impure Human Islet Fractions in the Presence of Alpha-1-Antitrypsin Prevents Insulin Cleavage and Improves Islet Recovery

    Science.gov (United States)

    Loganathan, G.; Dawra, R.K.; Pugazhenthi, S.; Wiseman, A.C.; Sanders, M.A.; Saluja, A.K.; Sutherland, D.E.R.; Hering, B.J.; Balamurugan, A.N.

    2010-01-01

    Background Exocrine tissue is commonly cotransplanted with islets in autografting and allotransplantation of impure preparations. Proteases and insulin are released by acinar cells and islets, respectively, during pretransplantation culture and also systemically after transplantation. We hypothesized that released proteases could cleave insulin molecules and that addition of alpha 1 antitrypsin (A1AT) to impure islet cultures would block this cleavage, improving islet recovery and function. Methods Trypsin, chymotrypsin, and elastase (TCE) activity and insulin levels were measured in culture supernates of pure (n = 5) and impure (n = 5) islet fractions, which were isolated from deceased donors. SDS-PAGE was used to detect insulin after incubation with proteases. We assessed the effects of A1AT supplementation (0.5 mg/mL; n = 4] on TCE activity, insulin levels, culture recovery, and islet quality. The ultrastructure of islets exposed to TCE versus control medium was examined using electron microscopy (EM). Results Protease (TCE) activity in culture supernates was directly proportional to the percentage purity of islets: pure, impure, or highly impure. Increasingly lower levels of insulin were detected in culture supernates with higher protease activity levels. Insulin levels measured in supernates of 2000 IE aliquots of impure and highly impure islet preparations were 61 ± 23.7% and 34 ± 33% of that in pure preparations, respectively. Incubation with commercially available proteases (TCE) or exocrine acinar cell supernates cleaved insulin molecules as assessed using SDS-PAGE. Addition of A1AT to impure islet preparations reduced protease activity and restored normal insulin levels as detected using enzyme-linked immunosorbent assay (ELISA) and SDS-PAGE of culture supernates. A1AT improved insulin levels to 98% ± 1.3% in impure and 78% ± 34.2% in highly impure fractions compared with pure islet fractions. A1AT supplementation improved postculture recovery of

  14. Alpha 1 Antitrypsin Inhibits Dendritic Cell Activation and Attenuates Nephritis in a Mouse Model of Lupus.

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    Ahmed S Elshikha

    Full Text Available Systemic lupus erythematosus (SLE is an autoimmune disorder with a worldwide distribution and considerable mortality and morbidity. Although the pathogenesis of this disease remains elusive, over-reactive dendritic cells (DCs play a critical role in the disease development. It has been shown that human alpha-1 antitrypsin (hAAT has protective effects in type 1 diabetes and rheumatoid arthritis mouse models. In the present study, we tested the effect of AAT on DC differentiation and functions, as well as its protective effect in a lupus-prone mouse model. We showed that hAAT treatment significantly inhibited LPS (TLR4 agonist and CpG (TLR9 agonist -induced bone-marrow (BM-derived conventional and plasmacytoid DC (cDC and pDC activation and reduced the production of inflammatory cytokines including IFN-I, TNF-α and IL-1β. In MRL/lpr mice, hAAT treatment significantly reduced BM-derived DC differentiation, serum autoantibody levels, and importantly attenuated renal pathology. Our results for the first time demonstrate that hAAT inhibits DC activation and function, and it also attenuates autoimmunity and renal damage in the MRL/lpr lupus model. These results imply that hAAT has a therapeutic potential for the treatment of SLE in humans.

  15. Alpha-1 antitrypsin prevents the development of preeclampsia through suppression of oxidative stress

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    Yaling eFeng

    2016-05-01

    Full Text Available Preeclampsia (PE and its complications have become the leading cause of maternal and fetal morbidity and mortality in the world. And the development of PE is still barely predictable and thus challenging to prevent and manage clinically. Oxidative stress contributes to the development of the disease. Our previous study demonstrated that exogenous Alpha-1 antitrypsin (AAT played a cytoprotective role in vascular endothelial cell by suppressing oxidative stress. In this study, we aim to investigate whether AAT contributes to the development of PE, and to identify the mechanism behind these effects. We found that AAT levels were significantly decreased in placenta tissues from women with PE compared that of healthy women. Notably, we demonstrate that AAT injection is able to relieve the high blood pressure and reduce urine protein levels in a dose-dependent manner in PE mice. In addition, our results showed that AAT injection exhibited an anti-oxidative stress role by significantly reducing PE mediated-upregulation of ROS, MMP9 and MDA, and increasing the levels of SOD, eNOS and GPx with increased dosage of AAT. Furthermore, we found that AAT injection inactivated PE mediated activation of PAK/STAT1/p38 signaling. These findings were confirmed in human samples. In conclusion, our study suggests that exogenous AAT injection increases the antioxidants and suppresses oxidative stress, and subsequent prevention of PE development through inactivation of STAT1/p38 signaling. Thus, AAT would become a potential strategy for PE therapy.

  16. Alpha-1 Antitrypsin Prevents the Development of Preeclampsia Through Suppression of Oxidative Stress.

    Science.gov (United States)

    Feng, Yaling; Xu, Jianjuan; Zhou, Qin; Wang, Rong; Liu, Nin; Wu, Yanqun; Yuan, Hua; Che, Haisha

    2016-01-01

    Preeclampsia (PE) and its complications have become the leading cause of maternal and fetal morbidity and mortality in the world. And the development of PE is still barely predictable and thus challenging to prevent and manage clinically. Oxidative stress contributes to the development of the disease. Our previous study demonstrated that exogenous Alpha-1 antitrypsin (AAT) played a cytoprotective role in vascular endothelial cell by suppressing oxidative stress. In this study, we aim to investigate whether AAT contributes to the development of PE, and to identify the mechanism behind these effects. We found that AAT levels were significantly decreased in placenta tissues from women with PE compared that of healthy women. Notably, we demonstrate that AAT injection is able to relieve the high blood pressure and reduce urine protein levels in a dose-dependent manner in PE mice. In addition, our results showed that AAT injection exhibited an anti-oxidative stress role by significantly reducing PE mediated-upregulation of ROS, MMP9 and MDA, and increasing the levels of SOD, eNOS, and GPx with increased dosage of AAT. Furthermore, we found that AAT injection inactivated PE mediated activation of PAK/STAT1/p38 signaling. These findings were confirmed in human samples. In conclusion, our study suggests that exogenous AAT injection increases the antioxidants and suppresses oxidative stress, and subsequent prevention of PE development through inactivation of STAT1/p38 signaling. Thus, AAT would become a potential strategy for PE therapy.

  17. Diabetic retinopathy: could the alpha-1 antitrypsin be a therapeutic option?

    Directory of Open Access Journals (Sweden)

    Gustavo Ortiz

    2014-01-01

    Full Text Available Diabetic retinopathy is one of the most important causes of blindness. The underlying mechanisms of this disease include inflammatory changes and remodeling processes of the extracellular-matrix (ECM leading to pericyte and vascular endothelial cell damage that affects the retinal circulation. In turn, this causes hypoxia leading to release of vascular endothelial growth factor (VEGF to induce the angiogenesis process. Alpha-1 antitrypsin (AAT is the most important circulating inhibitor of serine proteases (SERPIN. Its targets include elastase, plasmin, thrombin, trypsin, chymotrypsin, proteinase 3 (PR-3 and plasminogen activator (PAI. AAT modulates the effect of protease-activated receptors (PARs during inflammatory responses. Plasma levels of AAT can increase 4-fold during acute inflammation then is so-called acute phase protein (APPs. Individuals with low serum levels of AAT could develop disease in lung, liver and pancreas. AAT is involved in extracellular matrix remodeling and inflammation, particularly migration and chemotaxis of neutrophils. It can also suppress nitric oxide (NO by nitric oxide sintase (NOS inhibition. AAT binds their targets in an irreversible way resulting in product degradation. The aim of this review is to focus on the points of contact between multiple factors involved in diabetic retinopathy and AAT resembling pleiotropic effects that might be beneficial.

  18. Antigen-specific tolerance of human alpha1-antitrypsin induced by helper-dependent adenovirus.

    Science.gov (United States)

    Cerullo, V; McCormack, W; Seiler, M; Mane, V; Cela, R; Clarke, C; Rodgers, J R; Lee, B

    2007-12-01

    As efficient and less toxic virus-derived gene therapy vectors are developed, a pressing problem is to avoid immune response to the therapeutic gene product. Secreted therapeutic proteins potentially represent a special problem, as they are readily available to professional antigen-presenting cells throughout the body. Some studies suggest that immunity to serum proteins can be avoided in some mouse strains by using tissue-specific promoters. Here we show that expression of human alpha1-antitrypsin (AAT) was nonimmunogenic in the immune-responsive strain C3H/HeJ, when expressed from helper-dependent (HD) vectors using ubiquitous as well as tissue-specific promoters. Coadministration of less immunogenic HD vectors with an immunogenic first-generation vector failed to immunize, suggesting immune suppression rather than immune stealth. Indeed, mice primed with HD vectors were tolerant to immune challenge with hAAT emulsified in complete Freund's adjuvant. Such animals developed high-titer antibodies to coemulsified human serum albumin, showing that tolerance was antigen specific. AAT-specific T cell responses were depressed in tolerized animals, suggesting that tolerance affects both T and B cells. These results are consistent with models of high-dose tolerance of B cells and certain other suppressive mechanisms, and suggest that a high level of expression from HD vectors can be sufficient to induce specific immune tolerance to serum proteins.

  19. Functional unfolding of alpha1-antitrypsin probed by hydrogen-deuterium exchange coupled with mass spectrometry.

    Science.gov (United States)

    Baek, Je-Hyun; Yang, Won Suk; Lee, Cheolju; Yu, Myeong-Hee

    2009-05-01

    The native state of alpha(1)-antitrypsin (alpha(1)AT), a member of the serine protease inhibitor (serpin) family, is considered a kinetically trapped folding intermediate that converts to a more stable form upon complex formation with a target protease. Although previous structural and mutational studies of alpha(1)AT revealed the structural basis of the native strain and the kinetic trap, the mechanism of how the native molecule overcomes the kinetic barrier to reach the final stable conformation during complex formation remains unknown. We hypothesized that during complex formation, a substantial portion of the molecule undergoes unfolding, which we dubbed functional unfolding. Hydrogen-deuterium exchange coupled with ESI-MS was used to analyze this serpin in three forms: native, complexing, and complexed with bovine beta-trypsin. Comparing the deuterium content at the corresponding regions of these three samples, we probed the unfolding of alpha(1)AT during complex formation. A substantial portion of the alpha(1)AT molecule unfolded transiently during complex formation, including not only the regions expected from previous structural studies, such as the reactive site loop, helix F, and the following loop, but also regions not predicted previously, such as helix A, strand 6 of beta-sheet B, and the N terminus. Such unfolding of the native interactions may elevate the free energy level of the kinetically trapped native serpin sufficiently to cross the transition state during complex formation. In the current study, we provide evidence that protein unfolding has to accompany functional execution of the protein molecule.

  20. Alpha-1 antitrypsin gene polymorphism in Chronic Obstructive Pulmonary Disease (COPD

    Directory of Open Access Journals (Sweden)

    Sabri Denden

    2010-01-01

    Full Text Available Alpha-1-antitrypsin (AAT plays an important role in the pathogenesis of emphysema, the pathological lesion underlying the majority of the manifestations of Chronic Obstructive Pulmonary Disease (COPD. In this study we tested the hypothesis that common AAT polymorphisms influence the risk of developing COPDs. We investigated PiM1 (Ala213Val, PiM2 (Arg101His, PiM3 (Glu376Asp, PiS (Glu264Val and PiZ (Glu342Lys SERPINA1 alleles in 100 COPD patients and 200 healthy controls. No significant differences were observed in allele frequencies between COPD patients and controls, neither did haplotype analysis show significant differences between the two groups. A cross-sectional study revealed no significant relationship between common SERPINA1 polymorphisms (PiM1, PiM2, PiM3 and the emphysematous type of COPD. In addition, FEV1 annual decline, determined during a two-year follow up period, revealed no difference among carriers of the tested polymorphisms.

  1. The Influence of Cigarette Smoking on Gingival Bleeding and Serum Concentrations of Haptoglobin and Alpha 1-Antitrypsin

    Directory of Open Access Journals (Sweden)

    Fouad H. Al-Bayaty

    2013-01-01

    Full Text Available The objectives of this study were to evaluate the influence of cigarette smoking on gingival bleeding and serum concentrations of cotinine, haptoglobin, and alpha 1-antitrypsin in Malaysian smokers. A total of 197 male smokers and nonsmokers were recruited for this study. Plaque index, bleeding on probing (BOP, and levels of serum cotinine, haptoglobin, and alpha 1-antitrypsin were evaluated. The data were analyzed using SPSS version 20.0, with the significance level set at α≤0.05. Linear regression analyses were performed. The mean cigarette consumption per day was 13.39±5.75 cigarettes; the mean duration was 16.03±8.78 years. Relatively low BOP values (26.05±1.48 and moderate plaque indexes (51.35±11.27 were found. The levels of serum cotinine (106.9±30.71 ng/dL, haptoglobin (76.04±52.48 mg/dL, and alpha 1-antitrypsin (141.90±18.40 mg/dL were significantly higher in smokers compared to non-smokers. Multiple logistic regression models for all variables and smokers demonstrated observed differences between BOP, the number of cigarettes per day, and duration of smoking, while serum cotinine, haptoglobin and alpha-1 antitrypsin levels showed no significant differences. Duration of smoking (years and the cotinine level in serum showed a significant correlation with plaque index. The present analysis demonstrated that the duration of smoking in years, but not the number of cigarettes smoked per day, was associated with reduced gingival bleeding in smokers.

  2. Alpha-1 Antitrypsin Gene Therapy Ameliorates Bone Loss in Ovariectomy-Induced Osteoporosis Mouse Model.

    Science.gov (United States)

    Akbar, Mohammad Ahsanul; Cao, Jay J; Lu, Yuanqing; Nardo, David; Chen, Mong-Jen; Elshikha, Ahmed S; Ahamed, Rubina; Brantly, Mark; Holliday, L Shannon; Song, Sihong

    2016-09-01

    Osteoporosis is a major healthcare burden affecting mostly postmenopausal women characterized by compromised bone strength and increased risk of fragility fracture. Although pathogenesis of this disease is complex, elevated proinflammatory cytokine production is clearly involved in bone loss at menopause. Therefore, anti-inflammatory strategies hold a great potential for the prevention of postmenopausal osteoporosis. In this study, we investigated the effect of gene therapy of recombinant adeno-associated virus (rAAV)-mediated human alpha-1 antitrypsin (hAAT), a multifunctional protein that has anti-inflammatory property, on bone loss in an ovariectomy-induced osteoporosis mouse model. Adult ovariectomized (OVX) mice were intraperitoneally (i.p.) injected with hAAT (protein therapy), rAAV8-CB-hAAT (gene therapy), or phosphate buffer saline (PBS). Age-matched and sham-operated animals were used as controls. Eight weeks after the treatment, animals were sacrificed and bone-related biomarkers and vertebral bone structure were evaluated. Results showed that hAAT gene therapy significantly decreased serum IL-6 level and receptor activator of NF-κB (RANK) gene expression in bone. Importantly, hAAT gene therapy increased bone volume/total volume and decreased structure model index (SMI) compared to PBS injection in OVX mice. These results demonstrate that hAAT gene therapy by rAAV vector efficiently mitigates bone loss possibly through inhibition of proinflammatory cytokine IL-6 and RANK gene expression. Considering the safety profile of hAAT and rAAV vector in humans, our results provide a new alternative for the treatment of osteoporosis.

  3. Rapid renal alpha-1 antitrypsin gene induction in experimental and clinical acute kidney injury.

    Directory of Open Access Journals (Sweden)

    Richard A Zager

    Full Text Available Alpha-1-antitrypsin (AAT is a hepatic stress protein with protease inhibitor activity. Recent evidence indicates that ischemic or toxic injury can evoke selective changes within kidney that resemble a hepatic phenotype. Hence, we tested the following: i Does acute kidney injury (AKI up-regulate the normally renal silent AAT gene? ii Does rapid urinary AAT excretion result? And iii Can AAT's anti-protease/anti-neutrophil elastase (NE activity protect injured proximal tubule cells? CD-1 mice were subjected to ischemic or nephrotoxic (glycerol, maleate, cisplatin AKI. Renal functional and biochemical assessments were made 4-72 hrs later. Rapidly following injury, 5-10 fold renal cortical and isolated proximal tubule AAT mRNA and protein increases occurred. These were paralleled by rapid (>100 fold increases in urinary AAT excretion. AKI also induced marked increases in renal cortical/isolated proximal tubule NE mRNA. However, sharp NE protein levels declines resulted, which strikingly correlated (r, -0.94 with rising AAT protein levels (reflecting NE complexing by AAT/destruction. NE addition to HK-2 cells evoked ∼95% cell death. AAT completely blocked this NE toxicity, as well as Fe induced oxidant HK-2 cell attack. Translational relevance of experimental AAT gene induction was indicated by ∼100-1000 fold urinary AAT increases in 22 AKI patients (matching urine NGAL increases. We conclude: i AKI rapidly up-regulates the renal cortical/proximal tubule AAT gene; ii NE gene induction also results; iii AAT can confer cytoprotection, potentially by blocking/reducing cytotoxic NE accumulation; and iv marked increases in urinary AAT excretion in AKI patients implies clinical relevance of the AKI- AAT induction pathway.

  4. Alpha-1 antitrypsin protein and gene therapies decrease autoimmunity and delay arthritis development in mouse model

    Directory of Open Access Journals (Sweden)

    Atkinson Mark A

    2011-02-01

    Full Text Available Abstract Background Alpha-1 antitrypsin (AAT is a multi-functional protein that has anti-inflammatory and tissue protective properties. We previously reported that human AAT (hAAT gene therapy prevented autoimmune diabetes in non-obese diabetic (NOD mice and suppressed arthritis development in combination with doxycycline in mice. In the present study we investigated the feasibility of hAAT monotherapy for the treatment of chronic arthritis in collagen-induced arthritis (CIA, a mouse model of rheumatoid arthritis (RA. Methods DBA/1 mice were immunized with bovine type II collagen (bCII to induce arthritis. These mice were pretreated either with hAAT protein or with recombinant adeno-associated virus vector expressing hAAT (rAAV-hAAT. Control groups received saline injections. Arthritis development was evaluated by prevalence of arthritis and arthritic index. Serum levels of B-cell activating factor of the TNF-α family (BAFF, antibodies against both bovine (bCII and mouse collagen II (mCII were tested by ELISA. Results Human AAT protein therapy as well as recombinant adeno-associated virus (rAAV8-mediated hAAT gene therapy significantly delayed onset and ameliorated disease development of arthritis in CIA mouse model. Importantly, hAAT therapies significantly reduced serum levels of BAFF and autoantibodies against bCII and mCII, suggesting that the effects are mediated via B-cells, at least partially. Conclusion These results present a new drug for arthritis therapy. Human AAT protein and gene therapies are able to ameliorate and delay arthritis development and reduce autoimmunity, indicating promising potential of these therapies as a new treatment strategy for RA.

  5. Massive ascites and the heterozygous alpha 1 antitrypsin (α1AT) living related donor liver in the homozygous child.

    Science.gov (United States)

    Khorsandi, Shirin E; Thompson, Richard; Vilca-Melendez, Hector; Dhawan, Anil; Heaton, Nigel

    2018-02-01

    The following is a short report on the use of a heterozygous (PiMZ) alpha 1 antitrypsin (α1AT) living related donor liver in a homozygous (PiZ) child that was complicated by massive ascites early after transplant. This clinical report is then followed by a brief summary of present knowledge on the α 1 AT protein and management of massive ascites in the pediatric liver transplant recipient. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  6. Gastric clearance of alpha-1-antitrypsin under cimetidine perfusion. New test to detect protein-losing gastropathy

    International Nuclear Information System (INIS)

    Florent, C.; Vidon, N.; Flourie, B.; Carmantrand, A.; Zerbani, A.; Maurel, M.; Bernier, J.J.

    1986-01-01

    Gastric losses of plasma are usually measured with radiolabeled macromolecules. This method is expensive and cumbersome. Direct measurement of exudated plasma proteins are ineffective since proteins are denaturated by acidic gastric juice and pepsin. It was recently shown that albumin measurement after immediate neutralization allowed detection of gastric protein losses, but this method is quite complex and time consuming. We studied alpha 1-antitrypsin and 51Cr-labeled protein clearance in gastric juice during normal saline and cimetidine (1.5 mg/kg/hr) infusion in six healthy volunteers and six patients with exudative gastropathy. alpha 1-Antitrypsin was measurable in all samples during cimetidine infusion: alpha 1-AT and 51Cr losses were significantly correlated (P less than 0.001). The upper limit of gastric alpha 1-AT clearance in controls was 0.86 ml/hr (mean + 2 SD). Using this value, there was no overlapping between patients and controls. The upper limit of 51Cr test was 1.87 ml/hr (mean + 2 SD) in controls but gastric clearance of 51Cr was below this value in one patient. This suggests that the measurement of alpha 1-AT gastric clearance during cimetidine perfusion is a good test to detect an exudative gastropathy. This test is inexpensive and lasts only 3 hr

  7. In vivo post-transcriptional gene silencing of alpha-1 antitrypsin by adeno-associated virus vectors expressing siRNA.

    Science.gov (United States)

    Cruz, Pedro E; Mueller, Christian; Cossette, Travis L; Golant, Alexandra; Tang, Qiushi; Beattie, Stuart G; Brantly, Mark; Campbell-Thompson, Martha; Blomenkamp, Keith S; Teckman, Jeffrey H; Flotte, Terence R

    2007-09-01

    alpha-1 Antitrypsin (AAT) deficiency is one of the most common genetic diseases in North America, with a carrier frequency of approximately 4% in the US population. Homozygosity for the most common mutation (Glu342Lys, PI(*)Z) leads to the synthesis of a mutant protein, which accumulates and polymerizes within hepatocytes rather than being efficiently secreted. This lack of secretion causes severe serum deficiency predisposing to chronic lung disease. Twelve to fifteen percent of patients with PI(*)ZZ also develop liver disease, which can be severe, even in infancy. This is thought to be due to toxic effects of the accumulated mutant Z-AAT within the hepatocyte. Thus, an approach to reduce AAT-deficient liver disease will likely require some mechanism to decrease the amount of Z-AAT within hepatocytes. In this report, we describe studies of small-interfering RNAs (siRNAs) designed to downregulate endogenous AAT within hepatocytes. Three different siRNA sequences were identified and cloned into a recombinant adeno-associated virus (rAAV) backbone, either singly or as a trifunctional (3X) construct. Each had activity independently, but the levels of AAT expression in cell culture models showed the greatest decrease with the 3X construct, resulting in levels that were five-fold lower than controls. The rAAV-3X-siRNA was then packaged into AAV8 capsids and used in vivo to transduce the livers of human Z-AAT overexpressing transgenic mice. Those studies showed a decrease in total human AAT, a clearing of Z-AAT accumulation by immunohistochemistry, and a decrease in monomer Z-AAT within the liver within 3 weeks after vector injection. The rAAV8-3X-siRNA vector may hold promise as a potential therapy for patients with AAT liver disease.

  8. Alpha-1-Antitrypsin Antagonizes Cisplatin-Induced Cytotoxicity in Prostate Cancer (PC3) and Melanoma Cancer (A375) Cell Lines.

    Science.gov (United States)

    Ljujic, Mila; Mijatovic, Sanja; Bulatovic, Mirna Z; Mojic, Marija; Maksimovic-Ivanic, Danijela; Radojkovic, Dragica; Topic, Aleksandra

    2017-04-01

    Increased circulating alpha-1-antitrypsin (AAT) correlates with cancer stage/aggressiveness, but its role in cancer biology is unclear. We revealed antagonistic effect of AAT to cisplatin-induced cytotoxicity in prostate (PC3) and melanoma (A375) cancer cell lines. Moreover, AAT abrogated cytotoxicity of MEK inhibitor U0126 in PC3 cell line. Weaker antagonistic effect of AAT on cytotoxicity of PI3/Akt and NF-kB inhibitors was also observed. In addition, cisplatin increased AAT gene expression in transfected PC3 cells. However, AAT derived from transfected PC3 cells did not antagonize cisplatin-induced cytotoxicity. In conclusion, these results suggest possible association between high circulating AAT and cisplatin resistance.

  9. Human Alpha-1-Antitrypsin (hAAT) therapy reduces renal dysfunction and acute tubular necrosis in a murine model of bilateral kidney ischemia-reperfusion injury

    NARCIS (Netherlands)

    Maicas, Nuria; van der Vlag, Johan; Bublitz, Janin; Florquin, Sandrine; Bakker-van Bebber, Marinka; Dinarello, Charles A; Verweij, Vivienne; Masereeuw, Roos|info:eu-repo/dai/nl/155644033; Joosten, Leo A; Hilbrands, Luuk B

    2017-01-01

    Several lines of evidence have demonstrated the anti-inflammatory and cytoprotective effects of alpha-1-antitrypsin (AAT), the major serum serine protease inhibitor. The aim of the present study was to investigate the effects of human AAT (hAAT) monotherapy during the early and recovery phase of

  10. Effect of Recombinant alpha1-Antitrypsin Fc-Fused (AAT-Fc)Protein on the Inhibition of Inflammatory Cytokine Production and Streptozotocin-Induced Diabetes

    NARCIS (Netherlands)

    Lee, S.; Lee, Y.; Hong, K.; Hong, J.; Bae, S.; Choi, J.; Jhun, H.; Kwak, A.; Kim, E.; Jo, S.; Dinarello, C.A.; Kim, S.

    2013-01-01

    alpha1-Antitrypsin (AAT) is a member of the serine proteinase inhibitor family that impedes the enzymatic activity of serine proteinases, including human neutrophil elastase, cathepsin G and neutrophil proteinase 3. Here, we expressed recombinant AAT by fusing the intact AAT gene to the constant

  11. Preclinical evaluation of a recombinant adeno-associated virus vector expressing human alpha-1 antitrypsin made using a recombinant herpes simplex virus production method.

    Science.gov (United States)

    Chulay, Jeffrey D; Ye, Guo-Jie; Thomas, Darby L; Knop, David R; Benson, Janet M; Hutt, Julie A; Wang, Gensheng; Humphries, Margaret; Flotte, Terence R

    2011-02-01

    Recombinant adeno-associated virus (rAAV) vectors offer promise for gene therapy of alpha-1 antitrypsin (AAT) deficiency. A toxicology study in mice evaluated intramuscular injection of an rAAV vector expressing human AAT (rAAV-CB-hAAT) produced using a herpes simplex virus (HSV) complementation system or a plasmid transfection (TFX) method at doses of 3 × 10(11) vg (1.2 × 10(13) vg/kg) for both vectors and 2 × 10(12) vg (8 × 10(13) vg/kg) for the HSV-produced vector. The HSV-produced vector had favorable in vitro characteristics in terms of purity, efficiency of transduction, and hAAT expression. There were no significant differences in clinical findings or hematology and clinical chemistry values between test article and control groups and no gross pathology findings. Histopathological examination demonstrated minimal to mild changes in skeletal muscle at the injection site, consisting of focal chronic interstitial inflammation and muscle degeneration, regeneration, and vacuolization, in vector-injected animals. At the 3 × 10(11) vg dose, serum hAAT levels were higher with the HSV-produced vector than with the TFX-produced vector. With the higher dose of HSV-produced vector, the increase in serum hAAT levels was dose-proportional in females and greater than dose-proportional in males. Vector copy numbers in blood were highest 24 hr after dosing and declined thereafter, with no detectable copies present 90 days after dosing. Antibodies to hAAT were detected in almost all vector-treated animals, and antibodies to HSV were detected in most animals that received the highest vector dose. These results support continued development of rAAV-CB-hAAT for treatment of AAT deficiency.

  12. Alpha-1 Antitrypsin Test

    Science.gov (United States)

    ... Culture Blood Gases Blood Ketones Blood Smear Blood Typing Blood Urea Nitrogen (BUN) BNP and NT-proBNP ... Luteinizing Hormone (LH) Lyme Disease Tests Magnesium Maternal Serum Screening, Second Trimester Measles and Mumps Tests Mercury ...

  13. Encapsulation of Alpha-1 antitrypsin in PLGA nanoparticles: In Vitro characterization as an effective aerosol formulation in pulmonary diseases

    Directory of Open Access Journals (Sweden)

    Pirooznia Nazanin

    2012-05-01

    Full Text Available Abstract Background Alpha 1- antitrypsin (α1AT belongs to the superfamily of serpins and inhibits different proteases. α1AT protects the lung from cellular inflammatory enzymes. In the absence of α1AT, the degradation of lung tissue results to pulmonary complications. The pulmonary route is a potent noninvasive route for systemic and local delivery. The aerosolized α1AT not only affects locally its main site of action but also avoids remaining in circulation for a long period of time in peripheral blood. Poly (D, L lactide-co glycolide (PLGA is a biodegradable and biocompatible polymer approved for sustained controlled release of peptides and proteins. The aim of this work was to prepare a wide range of particle size as a carrier of protein-loaded nanoparticles to deposit in different parts of the respiratory system especially in the deep lung. Various lactide to glycolide ratio of the copolymer was used to obtain different release profile of the drug which covers extended and rapid drug release in one formulation. Results Nonaqueous and double emulsion techniques were applied for the synthesis of nanoparticles. Nanoparticles were characterized in terms of surface morphology, size distribution, powder X-ray diffraction (XRD, encapsulation efficiency, in vitro drug release, FTIR spectroscopy and differential scanning calorimetry (DSC. To evaluate the nanoparticles cytotoxicity, cell cytotoxicity test was carried out on the Cor L105 human epithelial lung cancer cell line. Nanoparticles were spherical with an average size in the range of 100 nm to 1μ. The encapsulation efficiency was found to be higher when the double emulsion technique was applied. XRD and DSC results indicated that α1AT encapsulated in the nanoparticles existed in an amorphous or disordered-crystalline status in the polymer matrix. The lactic acid to glycolic acid ratio affects the release profile of α1AT. Hence, PLGA with a 50:50 ratios exhibited the ability to release

  14. Extinction of alpha1-antitrypsin expression in cell hybrids is independent of HNF1alpha and HNF4 and involves both promoter and internal DNA sequences.

    OpenAIRE

    Bulla, G A

    1999-01-01

    In rat hepatoma x fibroblast somatic cell hybrids, extinction of rat alpha1-antitrypsin (alpha1AT) gene expression is accompanied by the loss of liver-enriched transcription factors hepatocyte nuclear factor 1 (HNF1alpha) and hepatocyte nuclear factor 4 (HNF4). Previous analysis showed that forced expression of functional HNF1alpha failed to prevent extinction of the rat alpha1AT locus in cell hybrids. Here I show that ectopic co-expression of HNF1alpha plus HNF4 fails to prevent extinction o...

  15. Effects of Prolastin C (Plasma-Derived Alpha-1 Antitrypsin) on the acute inflammatory response in patients with ST-segment elevation myocardial infarction (from the VCU-alpha 1-RT pilot study)

    NARCIS (Netherlands)

    Abbate, A.; Tassell, B.W. Van; Christopher, S.; Abouzaki, N.A.; Sonnino, C.; Oddi, C.; Carbone, S.; Melchior, R.D.; Gambill, M.L.; Roberts, C.S.; Kontos, M.C.; Peberdy, M.A.; Toldo, S.; Vetrovec, G.W.; Biondi-Zoccai, G.; Dinarello, C.A.

    2015-01-01

    Alpha-1 antitrypsin (AAT) has broad anti-inflammatory and immunomodulating properties in addition to inhibiting serine proteases. Administration of human plasma-derived AAT is protective in models of acute myocardial infarction in mice. The objective of this study was to determine the safety and

  16. TISSUE INHIBITOR OF METALLOPROTEINASE 1, MATRIX METALLOPROTEINASE 9, ALPHA-1 ANTITRYPSIN, METALLOTHIONEIN AND UROKINASE TYPE PLASMINOGEN ACTIVATOR RECEPTOR IN SKIN BIOPSIES FROM PATIENTS AFFECTED BY AUTOIMMUNE BLISTERING DISEASES

    Directory of Open Access Journals (Sweden)

    Ana Maria Abreu Velez

    2013-07-01

    Full Text Available Introduction: Proteinases and proteinase inhibitors have been described to play a role in autoimmune skin blistering diseases. We studied skin lesional biopsies from patients affected by several autoimmune skin blistering diseases for proteinases and proteinase inhibitors. Methods: We utilized immunohistochemistry to evaluate biopsies for alpha-1-antitrypsin, human matrix metalloproteinase 9 (MMP9, human tissue inhibitor of metalloproteinases 1 (TIMP-1, metallothionein and urokinase type plasminogen activator receptor (uPAR. We tested 30 patients affected by endemic pemphigus, 30 controls from the endemic area, and 15 normal controls. We also tested 30 biopsies from patients with bullous pemphigoid (BP, 20 with pemphigus vulgaris (PV, 8 with pemphigus foliaceus, and 14 with dermatitis herpetiformis (DH. Results: Contrary to findings in the current literature, most autoimmune skin blistering disease biopsies were negative for uPAR and MMP9. Only some chronic patients with El Bagre-EPF were positive to MMP9 in the dermis, in proximity to telocytes. TIMP-1 and metallothionein were positive in half of the biopsies from BP patients at the basement membrane of the skin, within several skin appendices, in areas of dermal blood vessel inflammation and within dermal mesenchymal-epithelial cell junctions.

  17. iTRAQ-Based Proteomics of Chronic Renal Failure Rats after FuShengong Decoction Treatment Reveals Haptoglobin and Alpha-1-Antitrypsin as Potential Biomarkers

    Directory of Open Access Journals (Sweden)

    Yu Yang

    2017-01-01

    Full Text Available Background. Chronic renal failure (CRF has become a global health problem and bears a huge economic burden. FuShengong Decoction (FSGD as traditional Chinese medicine has multiple pharmacological effects. Objectives. To understand the underlying molecular mechanism and signaling pathway involved in the FSGD treatment of CRF and screen differentially expressed proteins in rats with CRF treated with FSGD. Methods. Thirty-three male Sprague-Dawley rats were randomly divided into control group, CRF group, and FSGD group. Differentially expressed proteins were screened by iTRAQ coupled with nanoLC-MS/MS, and these identified proteins were later analyzed by GO, KEGG, and STRING. Additionally, haptoglobin (HP and alpha-1-antitrypsin (AAT were finally verified by ELISA, Western blot, and real time PCR. Results. A total of 417 proteins were identified. Nineteen differentially expressed proteins were identified in the FSGD group compared with the model group, of which 3 proteins were upregulated and 16 proteins were downregulated. Cluster analysis indicated that inflammatory response was associated with these proteins and complement and coagulation cascade pathways were predominantly involved. The validation methods further confirmed that the levels of HP and AAT were significantly increased. Conclusions. HP and AAT may be the important biomarkers in the pathogenesis of CRF and FSGD therapy.

  18. Urinary alpha-1 antitrypsin and CD59 glycoprotein predict albuminuria development in hypertensive patients under chronic renin-angiotensin system suppression.

    Science.gov (United States)

    Gonzalez-Calero, Laura; Martin-Lorenzo, Marta; de la Cuesta, Fernando; Maroto, Aroa S; Baldan-Martin, Montserrat; Ruiz-Hurtado, Gema; Pulido-Olmo, Helena; Segura, Julian; Barderas, Maria G; Ruilope, Luis M; Vivanco, Fernando; Alvarez-Llamas, Gloria

    2016-01-16

    Hypertension is a multi-factorial disease of increasing prevalence and a major risk factor for cardiovascular mortality even in the presence of adequate treatment. Progression of cardiovascular disease (CVD) occurs frequently during chronic renin-angiotensin-system (RAS) suppression, and albuminuria is a marker of CV risk. High prevalence of albuminuria in treated hypertensive patients has been demonstrated, but there are no available markers able to predict evolution. The aim of this study was the identification of novel indicators of albuminuria progression measurable in urine of diabetic and non-diabetic patients. 1143 hypertensive patients under chronic treatment were followed for a minimum period of 3 years. Among them, 105 diabetic and non-diabetic patients were selected and classified in three groups according to albuminuria development during follow-up: (a) patients with persistent normoalbuminuria; (b) patients developing de novo albuminuria; (c) patients with maintained albuminuria. Differential urine analysis was performed by 2D gel electrophoresis (2D-DIGE) and further confirmed by liquid chromatography-mass spectrometry. Non-parametric statistical tests were applied. CD59 glycoprotein and alpha-1 antitrypsin (AAT) resulted already altered in patients developing albuminuria de novo, with a similar response in those with maintained albuminuria. A prospective study in a sub-group of normoalbuminuric patients who were clinically followed up for at least 1 year from urine sampling, revealed CD59 and AAT proteins significantly varied in the urine collected from normoalbuminurics who will negatively progress, serving as predictors of future albuminuria development. CD59 and AAT proteins are significantly altered in hypertensive patients developing albuminuria. Interestingly, CD59 and AAT are able to predict, in normoalbuminuric individuals, who will develop albuminuria in the future, being potential predictors of vascular damage and CV risk. These findings

  19. Recent advances in understanding and treating COPD related to α1-antitrypsin deficiency.

    Science.gov (United States)

    Henao, Maria Paula; Craig, Timothy J

    2016-12-01

    Alpha-1-antitrypsin deficiency (AATD) is an orphan disease that predisposes individuals to COPD and liver disease. The following is a comprehensive review of AATD from epidemiology to treatment for physicians who treat COPD or asthma. Areas covered: In this comprehensive review of alpha-1-antitrypsin deficiency, we describe the historical perspective, genetics, epidemiology, clinical presentation and symptoms, screening and diagnosis, and treatments of the condition. Expert commentary: The two most important directions for advancing the understanding of AATD involve improving detection of the condition, especially in asymptomatic patients, and advancing knowledge of treatments directed specifically at AATD-related conditions. With regard to treatment for AATD-related conditions, research must continue to explore the implications and importance of augmentation therapy as well as consider new implementations that may prove more successful taking into consideration not only factors of pulmonary function and liver health, but also product availability and financial viability.

  20. Association of polymorphism of the alpha 1-antitrypsin gene with ...

    African Journals Online (AJOL)

    In order to determine the relationship between the polymorphisms of the AAT gene and milk production traits and SCS, the General Linear Model (GLM) procedure from the Statistical Analysis Software was used. SNP5504 affected milk fat percentage, SNP8178 affected milk protein percentage and SNP5609 and SNP5624 ...

  1. Alpha-1 antitrypsin phenotypes in patients with Klinefelter's syndrome

    Indian Academy of Sciences (India)

    Klinefelter's syndrome (KS) is the most common human sex chromosome disorder, with a prevalence of 1 in 660 men. The phenotype is variable, but the most constant findings are small and firm testes, decreased testosterone level, infertility, eunuchoid body proportion, increased height, and learning disabilities, due to the ...

  2. Alpha-1 antitrypsin phenotypes in patients with Klinefelter's syndrome

    Indian Academy of Sciences (India)

    1Department of Human Biology and Genetics, Institute of General and Molecular Pathology,. University of Tartu, Ravila Street 19, Tartu 50411, Estonia. 2Centre of Andrology, Tartu University Hospital, Puusepa Street 1a, Tartu 50406, Estonia. Introduction. Klinefelter's syndrome (KS) is the most common human sex.

  3. Association of polymorphism of alpha 1-antitrypsin gene with milk ...

    African Journals Online (AJOL)

    User

    number of human diseases (Majamaa et al., 2001; Lisowska-Myjak & Pachecka, 2007). Based on the role played by the AAT gene in humans, the aim of this study was to investigate possible associations between variants of the gene and milk production traits as well as SCS in Chinese Holstein dairy cattle. Materials and ...

  4. 25 Ways to Love Your Liver

    Science.gov (United States)

    ... Related Liver Disease Alpha 1 Antitrypsin Deficiency Autoimmune Hepatitis Benign Liver Tumors Biliary Atresia Cirrhosis of the Liver Galactosemia ... Related Liver Disease Alpha 1 Antitrypsin Deficiency Autoimmune Hepatitis Benign Liver Tumors Biliary Atresia Cirrhosis of the Liver Galactosemia ...

  5. Avaliação da concentração de alfa 1-antitripsina e da presença dos alelos S e Z em uma população de indivíduos sintomáticos respiratórios crônicos Determination of alpha 1-antitrypsin levels and of the presence of S and Z alleles in a population of patients with chronic respiratory symptoms

    Directory of Open Access Journals (Sweden)

    Heliane Guerra Serra

    2008-12-01

    Full Text Available OBJETIVO: Determinar a concentração de alfa 1-antitripsina (AAT e a prevalência dos alelos S e Z em indivíduos sintomáticos respiratórios crônicos. MÉTODOS: Pacientes com tosse crônica e dispnéia foram submetidos à avaliação clínica, espirometria, tomografia computadorizada de tórax, dosagem de AAT por nefelometria e pesquisa das mutações S e Z por reação em cadeia da polimerase. Foram consideradas como variáveis dependentes a concentração de AAT e o tabagismo. RESULTADOS: Dos 89 pacientes incluídos no estudo (44 mulheres; idade média, 51,3 ± 18,2 anos, os alelos S e Z foram detectados em 33,3% e 5,7%, respectivamente, com freqüência gênica dos alelos S e Z de 0,16 e 0,028. Dois pacientes tinham genótipo SZ (AAT 141 mg/dL (normal, Grupo 2, n = 57. A freqüência de fumantes foi igual nos dois grupos, com carga tabágica maior no Grupo 2. O alelo S estava presente em 13 e 14 pacientes dos Grupos 1 e 2, respectivamente, enquanto que o alelo Z estava presente em 2 e 1 paciente dos mesmos grupos. Não houve diferença nos testes de função pulmonar, nem na freqüência de bronquiectasias ou enfisema entre os dois grupos. Os valores espirométricos e as concentrações de AAT foram similares entre fumantes e não-fumantes. Bronquiectasias foram mais freqüentes entre os não fumantes, e enfisema foi mais freqüente entre os fumantes. CONCLUSÕES: Trinta pacientes apresentaram níveis de AAT abaixo da média esperada para os genótipos MM e MS, e este fato não pode ser explicado por uma freqüência maior dos alelos S e Z.OBJECTIVE: To determine the levels of alpha-1 antitrypsin (AAT and the presence of S and Z alleles in patients with chronic respiratory symptoms. METHODS: Patients with chronic cough and dyspnea were submitted to clinical evaluation, pulmonary function tests, high-resolution computed tomography, nephelometric determination of AAT and determination of S and Z alleles by polymerase chain reaction. Smoking

  6. Alpha-1 antitrypsin gene therapy prevented bone loss in ovariectomy induced osteoporosis mouse model

    Science.gov (United States)

    Osteoporosis is a major healthcare burden affecting mostly postmenopausal women characterized by compromised bone strength and increased risk of fragility fracture. Although pathogenesis of this disease is complex, elevated proinflammatory cytokine production is clearly involved in bone loss at meno...

  7. Alpha-1 antitrypsin phenotypes in patients with lung, prostate and breast cancer

    International Nuclear Information System (INIS)

    El-Akawi, Zeyad J.; Al-Hindawi, Fatin K.

    2004-01-01

    Determination of Alpha1-antitryspin (AT) phenotypes in Jordanian patients with lung, prostate and breast cancerto find a prevalent phenotype that could be recommended for the diagnosis of cancer. This study was conducted at Jordan University of Science and Technology, School of Medicine Jordan during the period May 2001 to May 2002. Alpha1-antitryspin (AT) phenotypes for 83 Jordanian cancer patients distributed as follows, 25 lung cancer, 25 prostate cancer and 33 with breast cancer were tested using isoelectric focusing gel electrophoresis and immunofluxation techniques. Isoelectric focusing results demonstrated that 96% of lung cancer patients were of PiMM phenotype and 4% of PiFM phenotype. All prostate cancer patients (100%) were found to be of PiMM and 3% PiMS. These findings demonstrated that there was no significant differences in the distribution of AT phenotypes among Jordanian patients with lung, prostae and breast cancerand they matched those reported for healthy individuals. Thus, we can nor recommand a given AT phentype for early diagnosis of the above mentioned types of cancer. (author)

  8. The role of α1 -antitrypsin Deficiency in the Pathogenesis of Antineutrophil Cytoplasmic Antibodies Associated Systemic Necrotizing Vasculitides

    Directory of Open Access Journals (Sweden)

    Alzouki Abdul-Nasser

    1999-01-01

    Full Text Available Alpha1-antitrypsin (D,1AT is the most abundant circulating protease inhibitor (Pi in human plasma. It has central function in controlling tissue degradation by inhibiting a large number of proteases including neutrophil elastase and proteinase 3 (PR3. PR3, the Wegner′s autoantigen, has been suggested to be involved in the pathogenesis of small-vessel systemic vasculitides. α1 AT deficiency (PiZ is frequent in Caucasian populations, and its homozygous state (PiZZ is known to predispose to lung emphysema and chronic liver disease. A strong correlation between heterozygous (PiZ and homozygous (PiZZ α1 AT deficiency and anti-neutrophil cytoplasmic autoantibodies (ANCA associated systemic nocrotizing vasculitides has recently been reported in various populations. In this review the pathogenesis of small-vessel vasculitides is outlined, focusing on the role of α1 AT deficiency. α1 AT has been suggested to have a crucial role as a protective protein in ANCA-associated vasculitic syndromes.

  9. Electrophoresis- and FRET-Based Measures of Serpin Polymerization.

    Science.gov (United States)

    Faull, Sarah V; Brown, Anwen E; Haq, Imran; Irving, James A

    2017-01-01

    Many serpinopathies, including alpha-1 antitrypsin (A1AT) deficiency, are associated with the formation of unbranched polymer chains of mutant serpins. In vivo, this deficiency is the result of mutations that cause kinetic or thermodynamic destabilization of the molecule. However, polymerization can also be induced in vitro from mutant or wild-type serpins under destabilizing conditions. The characteristics of the resulting polymers are dependent upon induction conditions. Due to their relationship to disease, serpin polymers, mainly those formed from A1AT, have been widely studied. Here, we describe Förster resonance energy transfer (FRET) and gel-based approaches for their characterization.

  10. Matrix metalloproteinase-9 predicts pulmonary status declines in α1-antitrypsin deficiency

    Directory of Open Access Journals (Sweden)

    Rames Alexis

    2011-03-01

    Full Text Available Abstract Background Matrix metalloproteinase-9 (MMP-9 may be important in the progression of emphysema, but there have been few longitudinal clinical studies of MMP-9 including pulmonary status and COPD exacerbation outcomes. Methods We utilized data from the placebo arm (n = 126 of a clinical trial of patients with alpha1-antitrypsin deficiency (AATD and emphysema to examine the links between plasma MMP-9 levels, pulmonary status, and COPD exacerbations over a one year observation period. Pulmonary function, computed tomography lung density, incremental shuttle walk test (ISWT, and COPD exacerbations were assessed at regular intervals over 12 months. Prospective analyses used generalized estimating equations to incorporate repeated longitudinal measurements of MMP-9 and all endpoints, controlling for age, gender, race-ethnicity, leukocyte count, and tobacco history. A secondary analysis also incorporated highly-sensitive C-reactive protein levels in predictive models. Results At baseline, higher plasma MMP-9 levels were cross-sectionally associated with lower FEV1 (p = 0.03, FVC (p Conclusions Increased plasma MMP-9 levels generally predicted pulmonary status declines, including worsening transfer factor and lung density as well as greater COPD exacerbations in AATD-associated emphysema.

  11. Modeling the influence of vitamin D deficiency on cigarette smoke-induced emphysema.

    Directory of Open Access Journals (Sweden)

    Mardi A. Crane-Godreau

    2013-06-01

    Full Text Available Chronic obstructive pulmonary disease (COPD is a major cause of morbidity and mortality worldwide. While the primary risk factor for COPD is cigarette smoke exposure, vitamin D deficiency has been epidemiologically implicated as a factor in the progressive development of COPD-associated emphysema. Because of difficulties inherent to studies involving multiple risk factors in the progression of COPD in humans, we developed a murine model in which to study the separate and combined effects of vitamin D deficiency and cigarette smoke exposure. During a 16 week period, mice were exposed to one of four conditions, control diet breathing room air (CD-NS, control diet with cigarette smoke exposure (CD-CSE, vitamin D deficient diet breathing room air (VDD-NS or vitamin D deficient diet with cigarette smoke exposure (VDD-CSE. At the end of the exposure period, the lungs were examined by a pathologist and separately by morphometric analysis. In parallel experiments, mice were anesthetized for pulmonary function testing followed by sacrifice and analysis. Emphysema (determined by an increase in alveolar mean linear intercept length was more severe in the VDD-CSE mice compared to control animals and animals exposed to VDD or CSE alone. The VDD-CSE and the CD-CSE mice had increased total lung capacity and increased static lung compliance. There was also a significant increase in the matrix metalloproteinase-9: tissue inhibitor of metalloproteinases-1 ratio in VDD-CSE mice compared with all controls. Alpha-1 antitrypsin expression was reduced in VDD-CSE mice as well. In summary, vitamin D deficiency, when combined with cigarette smoke exposure, seemed to accelerate the appearance of emphysemas, perhaps by virtue of an increased protease-antiprotease ratio in the combined VDD-CSE animals. These results support the value of our mouse model in the study of COPD.

  12. SP-A binds alpha1-antitrypsin in vitro and reduces the association rate constant for neutrophil elastase

    Directory of Open Access Journals (Sweden)

    Carrabino Natalia

    2005-12-01

    Full Text Available Abstract Background α1-antitrypsin and surfactant protein-A (SP-A are major lung defense proteins. With the hypothesis that SP-A could bind α1-antitrypsin, we designed a series of in vitro experiments aimed at investigating the nature and consequences of such an interaction. Methods and results At an α1-antitrypsin:SP-A molar ratio of 1:1, the interaction resulted in a calcium-dependent decrease of 84.6% in the association rate constant of α1-antitrypsin for neutrophil elastase. The findings were similar when SP-A was coupled with the Z variant of α1-antitrypsin. The carbohydrate recognition domain of SP-A appeared to be a major determinant of the interaction, by recognizing α1-antitrypsin carbohydrate chains. However, binding of SP-A carbohydrate chains to the α1-antitrypsin amino acid backbone and interaction between carbohydrates of both proteins are also possible. Gel filtration chromatography and turnover per inactivation experiments indicated that one part of SP-A binds several molar parts of α1-antitrypsin. Conclusion We conclude that the binding of SP-A to α1-antitrypsin results in a decrease of the inhibition of neutrophil elastase. This interaction could have potential implications in the physiologic regulation of α1-antitrypsin activity, in the pathogenesis of pulmonary emphysema, and in the defense against infectious agents.

  13. Reactivity of alpha 1-antitrypsin mutants against proteolytic enzymes of the kallikrein-kinin, complement, and fibrinolytic systems

    NARCIS (Netherlands)

    Patston, P.A.; Roodi, N.; Schifferli, J.A.; Bischoff, Rainer; Courtney, M.; Schapira, M.

    1990-01-01

    Increased extracellular proteolysis because of unregulated activation of blood coagulation, complement, and fibrinolysis is observed in thrombosis, shock, and inflammation. In the present study, we have examined whether the plasma kallikrein-kinin system, the classical pathway of complement, and the

  14. Cystic Fibrosis Chest X-Ray Findings: A Teaching Analog

    Science.gov (United States)

    2008-07-01

    Congenital Cystic Fibrosis Kartagener’s Syndrome Alpha-1 Antitrypsin Deficiency Bronchomalacia Yellow- Nail Syndrome Severe Inflammation...Mycobacterium (i.e. Tuberculosis) MRSA TORCHES Fungal Infection Obstructive Foreign Body Aspiration Bronchial Stricture Airway Mass/Tumor

  15. Aspectos pulmonares na deficiência de alfa-1-antitripsina

    Directory of Open Access Journals (Sweden)

    Luiza Érika Schmid Melo Neto

    2004-03-01

    Full Text Available RESUMO: A deficiência de α-1-antitripsina é uma desordem genética de herança autossómica recessiva, tendo como fenótipo mais comum o inibidor de protease tipo ZZ. A doença predomina em indivíduos brancos de origem europeia, e a sua frequência, tanto na Europa, como na América do Norte, é comparável à da fibrose quística (1:2000 a 1:7000. Os indivíduos com esta deficiência podem ser assintomáticos, sendo que a manifestação mais prevalente, também apontada como a maior causa de invalidez e morte nesses pacientes, é a doença pulmonar obstrutiva crónica. Nos indivíduos portadores da doença, o tabagismo constitui o factor de risco mais importante. A doença é muito pouco diagnosticada. Várias estratégias de tratamento têm sido utilizadas.REV PORT PNEUMOL 2004; X (2: 145-154 ABSTRACT: Alpha-1-antitrypsin deficiency is an autosomal hereditary disorder and the large majority of individuals with severe deficiency are protease inhibitor type ZZ. The disease occurs predominantly in white persons of European origin and its frequency in Europe and North America is comparable to that of cystic fibrosis (1 in 2000 to 1 in 7000. Persons with this deficiency may have no clinical manifestations, but the most prevalent clinical disorder associated, also pointed as the most frequent cause of disability and death, is chronic obstructive pulmonary disease. In those individuals, tobacco smoking is the major risk. The condition appears to be widely underdiagnosed, based on studies. Several strategies have been explored in the treatment of this deficiency.REV PORT PNEUMOL 2004; X (2: 145-154 Palavras-chave: alfa-1-antitripsina, doença pulmonar obstrutiva crónica, Key-words: alpha-1-antitripysin, chronic obstructive pulmonary disease

  16. Phase I trial of intramuscular injection of a recombinant adeno-associated virus serotype 2 alphal-antitrypsin (AAT) vector in AAT-deficient adults.

    Science.gov (United States)

    Brantly, Mark L; Spencer, L Terry; Humphries, Margaret; Conlon, Thomas J; Spencer, Carolyn T; Poirier, Amy; Garlington, Wendy; Baker, Dawn; Song, Sihong; Berns, Kenneth I; Muzyczka, Nicholas; Snyder, Richard O; Byrne, Barry J; Flotte, Terence R

    2006-12-01

    A phase I trial of intramuscular injection of a recombinant adeno-associated virus serotype 2 (rAAV2) alpha1-antitrypsin (AAT) vector was performed in 12 AAT-deficient adults, 10 of whom were male. All subjects were either homozygous for the most common AAT mutation (a missense mutation designated PI*Z) or compound heterozygous for PI*Z and another mutation known to cause disease. There were four dose cohorts, ranging from 2.1 x 10(12) vector genomes (VG) to 6.9 x 10(13) VG, with three subjects per cohort. Subjects were injected sequentially in a dose-escalating fashion with a minimum of 14 days between patients. Subjects who had been receiving AAT protein replacement discontinued that therapy 28 days before vector administration. There were no vector-related serious adverse events in any of the 12 participants. Vector DNA sequences were detected in the blood between 1 and 3 days after injection in nearly all patients receiving doses of 6.9 x 10(12) VG or higher. Anti-AAV2 capsid antibodies were present and rose after vector injection, but no other immune responses were detected. One subject who had not been receiving protein replacement exhibited low-level expression of wild-type M-AAT in the serum (82 nM), which was detectable 30 days after receiving an injection of 2.1 x 10(13) VG. Unfortunately, residual but declining M-AAT levels from the washout of the protein replacement elevated background levels sufficiently to obscure any possible vector expression in that range in most of the other individuals in the higher dose cohorts.

  17. A case-control study in chronic obstructive pulmonary disease

    African Journals Online (AJOL)

    Alpha-1 antitrypsin (AAT) deficiency is an inherited disorder that causes low levels of, or no AAT in the blood. The most common illness in adults with AAT deficiency is lung disease during the third and fourth decades of life. Most commonly, it is associated with chronic obstructive pulmonary disease (COPD). Mutations in the ...

  18. Alpha-1, are you in? (C)harlie (O)scar (P)appa (D)elta, over!

    African Journals Online (AJOL)

    The global numbers are expected to continue to increase as risk ... risk factor is alpha-1 antitrypsin (AAT) deficiency. This risk is particularly high if someone deficient in AAT also smokes. AAT inhibits a wide variety of proteases. It protects tissue from .... Perhaps collateral ventilation or interalveolar air drift through the pores ...

  19. AnovoCare Nursing Home, Stockhole Lane, Cloghran, Swords, Co. Dublin.

    LENUS (Irish Health Repository)

    McLean, Caitriona

    2009-01-01

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

  20. Inactivation of factor Xia in vivo: studies in chimpanzees and in humans

    NARCIS (Netherlands)

    Wuillemin, W. A.; Hack, C. E.; Bleeker, W. K.; Biemond, B. J.; Levi, M. [=Marcel M.; ten Cate, H.

    1996-01-01

    C1-inhibitor (C1Inh), antithrombin III (ATIII), alpha 1-antitrypsin (a1AT), and alpha 2-antiplasmin (a2AP) are known inhibitors of factor XIa (FXIa). However, their precise contribution to FXIa inactivation in vivo is not known. We investigated FXIa inactivation in chimpanzees and assessed the

  1. Hyperpolarised 3He MRI versus HRCT in COPD and normal volunteers: PHIL trial

    DEFF Research Database (Denmark)

    van Beek, E J R; Dahmen, A M; Stavngaard, T

    2009-01-01

    The aim of the present study was to apply hyperpolarised (HP) (3)He magnetic resonance imaging (MRI) to identify patients with chronic obstructive pulmonary disease (COPD) and alpha(1)-antitrypsin deficiency (alpha(1)-ATD) from healthy volunteers and compare HP (3)He MRI findings with high-resolu....... We showed the feasibility of a multicentre study using different magnetic resonance systems....

  2. Chronic hepatitis

    African Journals Online (AJOL)

    infection by four diagnostic systems: first generation and second generation. ELlSA, second generation recombinant immunoblot assay and nested polymerase chain reaction analysis. HepatoJogy 1992; 16: 300-305. 14. Van der Poel CL, ... Alpha-1-antitrypsin deficiency. Alcoholic hepatitis. Non-alcoholic steatohepatitis.

  3. Chronic obstructive pulmonary disease – diagnosis and ...

    African Journals Online (AJOL)

    family history of COPD, consider testing for alpha-1 antitrypsin deficiency. Assessment of severity. COPD and asthma are graded according to severity, and management recommendations are based on severity categories. Tradition- ally, management was decided on by lung function severity alone, but there has been.

  4. ORIGINAL ARTICLES Liver transplantation at Red Cross War ...

    African Journals Online (AJOL)

    The liver transplant programme for infants and children at Red. Cross War Memorial Children's Hospital is at present the only established paediatric service in sub-Saharan Africa. The first paediatric transplant was performed on 6 December 1987 for end-stage liver disease due to alpha-1-antitrypsin deficiency. The patient ...

  5. The Worst Headache of Life: Evaluation of Nontraumatic Subarachnoid Hemorrhage

    Science.gov (United States)

    2005-09-06

    include autosomal dominant polycystic kidney disease, hypertension, aortic coarctation , alpha-1 -antitrypsin deficiency, connective tissue diseases...which is highest immediately after the initial subarachnoid hemorrhage, is through early surgical or endovascular treatment of the ruptured aneurysm...Endovascular treatment is particularly useful in posterior circulation aneurysms, such as a basilar tip aneurysm, in which the surgical approach is

  6. Two novel nonradioactive polymerase chain reaction-based assays of dried blood spots, genomic DNA, or whole cells for fast, reliable detection of Z and S mutations in the alpha 1-antitrypsin gene

    DEFF Research Database (Denmark)

    Andresen, B S; Knudsen, I; Jensen, P K

    1992-01-01

    from individuals who are normal, heterozygous, or homozygous for the mutations. We show that the two assays can be performed with purified genomic DNA as well as with boiled blood spots. The new assays were validated by parallel testing with a technique in which PCR is combined with allele......-specific oligonucleotide (ASO) probes. In all cases tested the results obtained by the different techniques were in accordance. The new assays can be used for prenatal diagnostics and can be performed directly with boiled tissue samples. Because the new assays are easy to perform and reliable, we conclude...

  7. Health Deficiencies

    Data.gov (United States)

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

  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.

  9. 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 sa...

  10. Iron-Deficiency Anemia

    Medline Plus

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

  11. 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...

  12. Iron-Deficiency Anemia

    Medline Plus

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

  13. Iron-Deficiency Anemia

    Medline Plus

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

  14. Iron-Deficiency Anemia

    Science.gov (United States)

    ... Home / Iron-Deficiency Anemia Iron-Deficiency Anemia Also known as Leer en español ... bleeding Consuming less than recommended daily amounts of iron Iron-deficiency anemia can be caused by getting ...

  15. Iron-Deficiency Anemia

    Medline Plus

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

  16. Iron-Deficiency Anemia

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

  17. Vitamin Deficiency Anemia

    Science.gov (United States)

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

  18. 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 ...

  19. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... iron in your body causes iron-deficiency anemia. Lack of iron usually is due to blood loss, ... can help prevent overdosing in children. Because recent research supports concerns that iron deficiency during infancy and ...

  20. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... at 1 year of age. Women and Girls Women of childbearing age may be tested for iron-deficiency anemia, especially if they have: A history of iron-deficiency anemia Heavy blood loss during ...

  1. Iron-Deficiency Anemia

    Medline Plus

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

  2. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... absorb iron from the gastrointestinal tract (GI tract). Blood loss When you lose blood, you lose iron. ... other conditions that can cause iron-deficiency anemia. Blood tests to screen for iron-deficiency anemia To ...

  3. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... iron-deficiency anemia early in life affects later behavior, thinking, and mood during adolescence. Treating anemia in ... and is recruiting by invitation only. View more information about Donor Iron Deficiency Study - Red Blood Cells ...

  4. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... and young children and women are the two groups at highest risk for iron-deficiency anemia. Outlook Doctors usually can successfully treat iron-deficiency anemia. Treatment ... ...

  5. Iron-Deficiency Anemia

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

  6. Iron-Deficiency Anemia

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

  7. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... Health Topics Health Topics A-Z Clinical Trials Publications and Resources Health Education and Awareness The Science ... deficiency anemia. Endurance activities and athletes. Athletes, especially young females, are at risk for iron deficiency. Endurance ...

  8. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... risk for the condition. Women Women of childbearing age are at higher risk for iron-deficiency anemia ... periods. About 1 in 5 women of childbearing age has iron-deficiency anemia. Pregnant women also are ...

  9. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... iron-deficiency anemia can lead to heart problems, infections, problems with growth and development in children, and ... of the mouth, an enlarged spleen, and frequent infections. People who have iron-deficiency anemia may have ...

  10. Iron-Deficiency Anemia

    Medline Plus

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

  11. Iron-Deficiency Anemia

    Medline Plus

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

  12. Iron-Deficiency Anemia

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    Full Text Available ... and paler than normal when viewed under a microscope. Different tests help your doctor diagnose iron-deficiency ... if you have iron-deficiency anemia or another type of anemia. You may be diagnosed with iron- ...

  13. Iron-Deficiency Anemia

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

  14. Iron-Deficiency Anemia

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

  15. Iron-Deficiency Anemia

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

  16. Iron-Deficiency Anemia

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

  17. Iron-Deficiency Anemia

    Medline Plus

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

  18. Iron-Deficiency Anemia

    Medline Plus

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

  19. Iron-Deficiency Anemia

    Medline Plus

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

  20. Iron-Deficiency Anemia

    Medline Plus

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

  1. Iron-Deficiency Anemia

    Medline Plus

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

  2. 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) ...

  3. Iron-Deficiency Anemia

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

  4. Iron-Deficiency Anemia

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

  5. Iron-Deficiency Anemia

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

  6. Iron-Deficiency Anemia

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

  7. Iron-Deficiency Anemia

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    Full Text Available ... be at risk for iron-deficiency anemia. Lifestyle habits Certain lifestyle habits may increase your risk for iron-deficiency anemia, ... prevention and treatment of heart, lung, blood, and sleep disorders, including iron-deficiency anemia. Learn about the ...

  8. 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.

  9. Colour vision deficiency.

    Science.gov (United States)

    Simunovic, M P

    2010-05-01

    Colour vision deficiency is one of the commonest disorders of vision and can be divided into congenital and acquired forms. Congenital colour vision deficiency affects as many as 8% of males and 0.5% of females--the difference in prevalence reflects the fact that the commonest forms of congenital colour vision deficiency are inherited in an X-linked recessive manner. Until relatively recently, our understanding of the pathophysiological basis of colour vision deficiency largely rested on behavioural data; however, modern molecular genetic techniques have helped to elucidate its mechanisms. The current management of congenital colour vision deficiency lies chiefly in appropriate counselling (including career counselling). Although visual aids may be of benefit to those with colour vision deficiency when performing certain tasks, the evidence suggests that they do not enable wearers to obtain normal colour discrimination. In the future, gene therapy remains a possibility, with animal models demonstrating amelioration following treatment.

  10. LACTASE DEFICIENCY IN CHILDREN

    Directory of Open Access Journals (Sweden)

    V.A. Shcherbak

    2011-01-01

    Full Text Available The topic of the article is the lactase deficiency in children. The most frequent clinical manifestations — diarrhea and flatulence —are not specific to this pathology. Symptoms, typical for the majority of the diseases nosologies of the digestive system, lack of timely laboratory diagnosis, and, often, lack of pediatricians awareness about the specifics of this disease are the cause of lactase deficiency under-diagnostics. The article describes in detail the physiopathological mechanisms, clinical picture, diagnosis and dietary correction of lactase deficiency, the data concerning the prevalence of this disease are cited.Key words: lactose, lactase deficiency, children, health food.

  11. Iron-Deficiency Anemia

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    Full Text Available ... Precision Medicine Activities Obesity, Nutrition, and Physical Activity Population and ... Treatments may include dietary changes, medicines, and surgery. Severe iron-deficiency anemia may ...

  12. Iodine deficiency disorders

    International Nuclear Information System (INIS)

    Ali, S.M.

    1993-01-01

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

  13. Vitamin B12 deficiency

    DEFF Research Database (Denmark)

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

    2017-01-01

    , subclinical deficiency affects between 2.5% and 26% of the general population depending on the definition used, although the clinical relevance is unclear. B12 deficiency can affect individuals at all ages, but most particularly elderly individuals. Infants, children, adolescents and women of reproductive age...... are also at high risk of deficiency in populations where dietary intake of B12-containing animal-derived foods is restricted. Deficiency is caused by either inadequate intake, inadequate bioavailability or malabsorption. Disruption of B12 transport in the blood, or impaired cellular uptake or metabolism...

  14. Iron-Deficiency Anemia

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

  15. Panlobular emphysema in young intravenous Ritalin abusers

    International Nuclear Information System (INIS)

    Schmidt, R.A.; Glenny, R.W.; Godwin, J.D.; Hampson, N.B.; Cantino, M.E.; Reichenbach, D.D.

    1991-01-01

    We studied a distinctive group of young intravenous Ritalin abusers with profound obstructive lung disease. Clinically, they seemed to have severe emphysema, but the pathologic basis of their symptoms had not been investigated previously. Seven patients have died and been autopsied: in four, the lungs were fixed, inflated, dried, and examined in detail radiologically, grossly, microscopically, and by electron probe X-ray microanalysis. All seven patients had severe panlobular (panacinar) emphysema that tended to be more severe in the lower lung zones and that was associated with microscopic talc granulomas. Vascular involvement by talc granulomas was variable, but significant interstitial fibrosis was not present. Five patients were tested for alpha-1-antitrypsin deficiency and found to be normal, as were six similar living patients. These findings indicate that some intravenous drug abusers develop emphysema that clinically, radiologically, and pathologically resembles that caused by alpha-1-antitrypsin deficiency but which must have a different pathogenesis. Talc from the Ritalin tablets may be important, but the mechanism remains to be elucidated

  16. Iron-Deficiency Anemia

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    Full Text Available ... when used properly, can help prevent iron-deficiency anemia in infants and young children. Talk with your child's doctor ... and supplements, go to "How Is Iron-Deficiency Anemia Treated?" Infants and young children and women are the two ...

  17. Iron-Deficiency Anemia

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    Full Text Available ... term but can't take iron supplements by mouth. This therapy also is given to people who need immediate treatment for iron-deficiency anemia. Living With If you have iron-deficiency anemia, get ongoing care to make sure your iron levels are improving. ...

  18. 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

  19. 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

  20. MENTAL DEFICIENCY. SECOND EDITION.

    Science.gov (United States)

    HILLIARD, L.T.; KIRMAN, BRIAN H.

    REVISED TO INCLUDE LEGISLATIVE AND ADMINISTRATIVE PROCEDURES NEW IN BRITAIN SINCE THE 1957 EDITION, THE TEXT INCLUDES RECENT ADVANCES IN ETIOLOGY, PATHOLOGY, AND TREATMENT OF MENTAL DEFICIENCY. CONSIDERATION OF THE BACKGROUND OF MENTAL DEFICIENCY INCLUDES HISTORICAL AND LEGAL ASPECTS, THE SOCIAL BACKGROUND OF MENTAL DEFECT, PRENATAL CAUSES OF…

  1. Iron-Deficiency Anemia

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

  2. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... Home / < Back To Health Topics / Iron-Deficiency Anemia Iron-Deficiency Anemia Also known as Leer en español ... of growth and development. Inability To Absorb Enough Iron Even if you have enough iron in your ...

  3. G6PD Deficiency

    Science.gov (United States)

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

  4. Iron-Deficiency Anemia

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    Full Text Available ... other conditions to prevent you from developing iron-deficiency anemia. Foods that are good sources of iron include dried ... patterns. Increase your daily intake of iron-rich foods to help treat your iron-deficiency anemia. See Prevention strategies to learn about foods ...

  5. Iron-Deficiency Anemia

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

  6. Iron-Deficiency Anemia

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

  7. 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)....

  8. Iron-Deficiency Anemia

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    Full Text Available ... anemia if you have certain risk factors , including pregnancy. To prevent iron-deficiency anemia, your doctor may recommend you eat heart- ... infections Motor or cognitive development delays in ... with chronic conditions, iron-deficiency anemia can make their condition worse or result ...

  9. Iron-Deficiency Anemia

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

  10. Iron-Deficiency Anemia

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

  11. Iron-Deficiency Anemia

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

  12. Iron-Deficiency Anemia

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

  13. Iron-Deficiency Anemia

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

  14. Iron-Deficiency Anemia

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

  15. 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 ...

  16. Iron-Deficiency Anemia

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

  17. Deficiency of α-1-antitrypsin influences systemic iron homeostasis

    Directory of Open Access Journals (Sweden)

    Ghio AJ

    2013-01-01

    Full Text Available Andrew J Ghio,1 Joleen M Soukup,1 Judy H Richards,1 Bernard M Fischer,2 Judith A Voynow,2 Donald E Schmechel31US Environmental Protection Agency, Chapel Hill, NC, USA; 2Division of Pediatric Pulmonary Medicine, Department of Pediatrics,3Joseph and Kathleen Bryan Alzheimer Disease Research Center, Department of Medicine (Neurology, Duke University Medical Center, Durham, NC, USAAbstract: There is evidence that proteases and antiproteases participate in the iron homeostasis of cells and living systems. We tested the postulate that α-1 antitrypsin (A1AT polymorphism and the consequent deficiency of this antiprotease in humans are associated with a systemic disruption in iron homeostasis. Archived plasma samples from Alpha-1 Foundation (30 MM, 30 MZ, and 30 ZZ individuals were analyzed for A1AT, ferritin, transferrin, and C-reactive protein (CRP. Plasma samples were also assayed for metals using inductively coupled plasma atomic emission spectroscopy (ICPAES. Plasma levels of A1AT in MZ and ZZ individuals were approximately 60% and 20% of those for MM individuals respectively. Plasma ferritin concentrations in those with the ZZ genotype were greater relative to those individuals with either MM or MZ genotype. Plasma transferrin for MM, MZ, and ZZ genotypes showed no significant differences. Linear regression analysis revealed a significant (negative relationship between plasma concentrations of A1AT and ferritin while that between A1AT and transferrin levels was not significant. Plasma CRP concentrations were not significantly different between MM, MZ, and ZZ individuals. ICPAES measurement of metals confirmed elevated plasma concentrations of nonheme iron among ZZ individuals. Nonheme iron concentrations correlated (negatively with levels of A1AT. A1AT deficiency is associated with evidence of a disruption in iron homeostasis with plasma ferritin and nonheme iron concentrations being elevated among those with the ZZ genotype.Keywords: α-1

  18. Iron-Deficiency Anemia

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

  19. Iron-Deficiency Anemia

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

  20. Iron-Deficiency Anemia

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

  1. Iron-Deficiency Anemia

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

  2. Iron-Deficiency Anemia

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    Full Text Available ... is caused by strong muscle contractions and the impact of feet repeatedly striking the ground, such as ... Treatment will explain treatment-related complications or side effects. Diagnosis Iron-deficiency anemia may be detected during ...

  3. Iron-Deficiency Anemia

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

  4. Iron-Deficiency Anemia

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    Full Text Available ... Safety Sleep Science and Sleep Disorders Lung Diseases Heart and Vascular Diseases Precision Medicine Activities Obesity, Nutrition, ... symptoms. Severe iron-deficiency anemia can lead to heart problems, infections, problems with growth and development in ...

  5. Iron-Deficiency Anemia

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

  6. Iron-Deficiency Anemia

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

  7. Iron-Deficiency Anemia

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

  8. Iron-Deficiency Anemia

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    Full Text Available ... Heavy blood loss during their monthly periods Other risk factors for iron-deficiency anemia The Centers for Disease Control and Prevention (CDC) has developed guidelines for ...

  9. Iron-Deficiency Anemia

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    Full Text Available ... in which your blood has a lower than normal number of red blood cells. Red blood cells ... cells it does make have less hemoglobin than normal. Iron-deficiency anemia can cause fatigue (tiredness), shortness ...

  10. Iron-Deficiency Anemia

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    Full Text Available ... to improve health through research and scientific discovery. Improving health with current research Learn about the following ... donors for low iron stores. Reliable point-of-care testing may help identify iron deficiency before potentially ...

  11. Iron-Deficiency Anemia

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

  12. Iron-Deficiency Anemia

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

  13. Iron-Deficiency Anemia

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

  14. Iron-Deficiency Anemia

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

  15. Iron-Deficiency Anemia

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    Full Text Available ... Search Form Search the NHLBI, use the drop down list to select: the entire site, the Health ... who have iron-deficiency anemia develop restless legs syndrome (RLS). RLS is a disorder that causes a ...

  16. Manganese deficiency in plants

    DEFF Research Database (Denmark)

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

    2016-01-01

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

  17. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... Heavy Menstrual Bleeding (Centers for Disease Control and Prevention) Iron - Health Professional Fact Sheet (NIH) Iron Dietary Supplement Fact Sheet (NIH) Iron-Deficiency Anemia (National Library ...

  18. Iron-Deficiency Anemia

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

  19. Iron-Deficiency Anemia

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    Full Text Available ... a frequent blood donor living in New York City? This study is looking at how iron-deficiency ... National Institute of Health Department of Health and Human Services OIG USA.gov

  20. Iron-Deficiency Anemia

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    Full Text Available ... lead in their blood from their environment or water. Lead interferes with the body’s ability to make ... explain tests and procedures that your doctor may use to diagnose iron-deficiency anemia. Living With will ...

  1. Iron-Deficiency Anemia

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

  2. Iron-Deficiency Anemia

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

  3. Iron-Deficiency Anemia

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

  4. Iron-Deficiency Anemia

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

  5. Iron-Deficiency Anemia

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    Full Text Available ... need for iron increases during these periods of growth and development, and it may be hard to get the ... iron-deficiency anemia, red blood cells will be small in size with an MCV of less than ...

  6. Iron-Deficiency Anemia

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    Full Text Available ... at highest risk for iron-deficiency anemia. Special measures can help prevent the condition in these groups. ... is a complete blood count (CBC). The CBC measures many parts of your blood. This test checks ...

  7. Iron-Deficiency Anemia

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    Full Text Available ... test called a complete blood count (CBC) to see if you have lower than normal red blood ... iron-deficiency anemia: Check for bleeding. Look to see whether your tongue, nails, or inner lining of ...

  8. Iron-Deficiency Anemia

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

  9. Iron-Deficiency Anemia

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    Full Text Available ... iron in your body causes iron-deficiency anemia. Lack of iron usually is due to blood loss, ... preventing, diagnosing, and treating heart, lung, blood, and sleep disorders. Learn more about participating in a clinical ...

  10. Iron-Deficiency Anemia

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    Full Text Available ... in infants and small children Heavy menstrual periods Injury or surgery Urinary tract bleeding Consuming less than recommended daily amounts of iron Iron-deficiency anemia can be caused by getting less than the recommended daily ...

  11. Iron-Deficiency Anemia

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    Full Text Available ... Grants & Training Grants and Training Home Policies and Guidelines Funding Opportunities and Contacts Training and Career Development ... Study - Red Blood Cells From Iron-deficient Donors: Recovery and Storage Quality. Learn more about participating in ...

  12. Iron-Deficiency Anemia

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    Full Text Available ... diagnose iron-deficiency anemia. Living With will discuss what your doctor may recommend to prevent your iron- ... colon under sedation to view the colon directly. What if my doctor thinks something else is causing ...

  13. Iron-Deficiency Anemia

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

  14. Iron-Deficiency Anemia

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    Full Text Available ... people who have iron-deficiency anemia develop restless legs syndrome (RLS). RLS is a disorder that causes a strong urge to move the legs. This urge to move often occurs with strange ...

  15. Iron-Deficiency Anemia

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

  16. Iron-Deficiency Anemia

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

  17. Iron-Deficiency Anemia

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

  18. Iron-Deficiency Anemia

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    Full Text Available ... size of your liver and spleen Do a pelvic and rectal exam to check for internal bleeding ... bleeding in the stomach, upper intestines, colon, or pelvic organs. Treatment Treatment for iron-deficiency anemia will ...

  19. Iron-Deficiency Anemia

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

  20. Iron-Deficiency Anemia

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

  1. Iron-Deficiency Anemia

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

  2. Iron-Deficiency Anemia

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    Full Text Available ... recommended amounts of iron, in milligrams (mg) at different ages and stages of life. Until the teen ... mean corpuscular volume (MCV) that would suggest anemia. Different tests help your doctor screen for iron-deficiency ...

  3. Iron-Deficiency Anemia

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    Full Text Available ... can slow the absorption of iron. Screening and Prevention Eating a well-balanced diet that includes iron- ... deficiency anemia The Centers for Disease Control and Prevention (CDC) has developed guidelines for who should be ...

  4. Iron-Deficiency Anemia

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

  5. Iron-Deficiency Anemia

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

  6. Iron-Deficiency Anemia

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

  7. Iron-Deficiency Anemia

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

  8. Iron-Deficiency Anemia

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    Full Text Available ... mouth Pale skin Swelling or soreness of the tongue Common symptoms of iron-deficiency anemia include: Chest ... Check for bleeding. Look to see whether your tongue, nails, or inner lining of your eyelids are ...

  9. Iron-Deficiency Anemia

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

  10. Iron-Deficiency Anemia

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

  11. Iron-Deficiency Anemia

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

  12. Iron-Deficiency Anemia

    Science.gov (United States)

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

  13. Iron-Deficiency Anemia

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

  14. Vitamin D Deficiency

    Science.gov (United States)

    ... inflammation) • Some lymphomas, a type of cancer Other risk factors for vitamin D deficiency ... medications • Frequent falls in older adults, or a non-traumatic fracture (bone break without ...

  15. Iron-Deficiency Anemia

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

  16. Iron-Deficiency Anemia

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

  17. Iron-Deficiency Anemia

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

  18. Iron-Deficiency Anemia

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

  19. Iron-Deficiency Anemia

    Medline Plus

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

  20. Iron-Deficiency Anemia

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    Full Text Available ... can cause complications and may be life-threatening. Signs and Symptoms Common signs of iron-deficiency anemia ... abnormal heart rhythms and depression. Learn the warning signs of serious complications and have a plan Tell ...

  1. Iron-Deficiency Anemia

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

  2. Iron-Deficiency Anemia

    Medline Plus

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

  3. Iron-Deficiency Anemia

    Medline Plus

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

  4. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... MCV of less than 80 femtoliters (fL). Prevention strategies If you have certain risk factors , such as ... to iron-deficiency anemia. We are interested in studying in more detail how iron levels are regulated ...

  5. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... MCV of less than 80 femtoliters (fL). Prevention strategies If you have certain risk factors , such as ... infancy has lasting effects. We are interested in learning how having iron-deficiency anemia early in life ...

  6. Iron-Deficiency Anemia

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    Full Text Available ... GI tract. Inflammation from congestive heart failure or obesity . These chronic conditions can lead to inflammation that may cause iron-deficiency anemia. Are you curious about how ...

  7. Iron-Deficiency Anemia

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

  8. Iron-Deficiency Anemia

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    Full Text Available ... supports concerns that iron deficiency during infancy and childhood can have long-lasting, negative effects on brain health, the American Academy of Pediatrics recommends testing all ...

  9. Iron-Deficiency Anemia

    Medline Plus

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

  10. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... MCV of less than 80 femtoliters (fL). Prevention strategies If you have certain risk factors , such as ... Learn about exciting research areas that NHLBI is exploring about iron-deficiency anemia. Read more New treatments ...

  11. Iron-Deficiency Anemia

    Medline Plus

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

  12. Iron-Deficiency Anemia

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

  13. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... treat iron-deficiency anemia. These doctors include pediatricians, family doctors, gynecologists/obstetricians, and internal medicine specialists. A hematologist (a blood disease specialist), a gastroenterologist (a digestive system specialist), and ...

  14. Iron-Deficiency Anemia

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

  15. Iron-Deficiency Anemia

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

  16. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... iron-deficiency anemia can cause serious complications, including heart failure and development delays in children. Explore this Health ... bleeding in the GI tract. Inflammation from congestive heart failure or obesity . These chronic conditions can lead to ...

  17. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... All News NHLBI News NHLBI in the Press Research Features All Events Past Events Upcoming Events About ... NHLBI Entire Site Health Topics News & Resources Intramural Research Home / < Back To Health Topics / Iron-Deficiency Anemia ...

  18. Iron-Deficiency Anemia

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    Full Text Available ... the likelihood of bleeding in the GI tract. Inflammation from congestive heart failure or obesity . These chronic conditions can lead to inflammation that may cause iron-deficiency anemia. Are you ...

  19. Iron-Deficiency Anemia

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

  20. Iron-Deficiency Anemia

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

  1. Iron-Deficiency Anemia

    Medline Plus

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

  2. Iron-Deficiency Anemia

    Medline Plus

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

  3. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... also may help treat iron-deficiency anemia. Medical History Your doctor will ask about your signs and ... Reticulocytes are young, immature red blood cells. Over time, reticulocytes become mature red blood cells that carry ...

  4. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... to prevent you from developing iron-deficiency anemia. Foods that are good sources of iron include dried ... tofu, dried fruits, and dark green leafy vegetables. Foods rich in vitamin C, such as oranges, strawberries, ...

  5. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... breastfeeding women older than 18 need 9 mg. Problems absorbing iron Even if you consume the recommended ... prevention and treatment of heart, lung, blood, and sleep disorders, including iron-deficiency anemia. Learn about the ...

  6. Iron-Deficiency Anemia

    Medline Plus

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

  7. Iron-Deficiency Anemia

    Medline Plus

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

  8. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... as ice, dirt, paint, or starch. Restless legs syndrome Shortness of breath Weakness Complications Undiagnosed or untreated iron-deficiency anemia may cause the following complications: Depression Heart problems. If you ...

  9. Iron-Deficiency Anemia

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    Full Text Available ... breastfeeding women older than 18 need 9 mg. Problems absorbing iron Even if you consume the recommended ... infancy has lasting effects. We are interested in learning how having iron-deficiency anemia early in life ...

  10. Iron-Deficiency Anemia

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

  11. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... Older adults, especially those over age 65. Unhealthy environments Children who have lead in their blood from ... a frequent blood donor living in New York City? This study is looking at how iron-deficiency ...

  12. Iron-Deficiency Anemia

    Medline Plus

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

  13. Factor XI deficiency

    Directory of Open Access Journals (Sweden)

    Jayme Diamant

    2004-06-01

    Full Text Available We describe a patient with a prolonged aPTT who was diagnosedas having factor XI deficiency after a rather large hematoma wasformed after angiography. Factor XI deficiency affects 1 in 1 millionpeople, but it is more common in Ashkenazim with a gene frequencyof 5% to 11%, being 0.3% homozygotes. These individuals usuallydo not present hemorrhagic events, except in cases of trauma orsurgery. These patients should be identified by routine coagulationscreening; bleeding could be prevented by use of fresh humanplasma or plasma concentrates.

  14. Vitamin Excess and Deficiency.

    Science.gov (United States)

    Diab, Liliane; Krebs, Nancy F

    2018-04-01

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

  15. Iron-Deficiency Anemia

    Medline Plus

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

  16. 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...

  17. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... funding on iron-deficiency anemia. We stimulate high-impact research. Our Trans-Omics for Precision Medicine (TOPMed) Program now includes participants with anemia, which may help us understand how genes contribute to differences in disease severity and how patients respond to treatment. The ...

  18. Iron-Deficiency Anemia

    Medline Plus

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

  19. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... Follow a high-fiber diet. Large amounts of fiber can slow the absorption of iron. Screening and Prevention Eating a well-balanced diet that includes iron-rich foods may help you prevent iron-deficiency anemia. Taking ...

  20. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... donors for low iron stores. Reliable point-of-care testing may help identify iron deficiency before potentially harmful donations and protect individuals from needing iron supplementation. Advancing research for improved health In support of our mission , we are committed ...

  1. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... proof packages for supplements can help prevent overdosing in children. Because recent research supports concerns that iron deficiency ... within months. Supplements come in pill form or in drops for children. Large amounts of iron can be harmful, so ...

  2. Iron deficiency in children

    African Journals Online (AJOL)

    Anaemia is a worldwide health problem affecting developed and developing countries. Children <5 years of age and women of child-bearing age are the most vulnerable. Iron deficiency anaemia (IDA) ranked 15th and 14th in the global disability-adjusted life-years in. 1990 and 2010, respectively.[1] Globally, the ...

  3. 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'.

  4. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... ages of 14 and 50 years need more iron than boys and men of the same age. Women are at higher ... anemia. In iron-deficiency anemia, blood levels of iron will be low, or less than 10 micromoles per liter (mmol/L) for both men and women. Normal levels are 10 to 30 ...

  5. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... develop restless legs syndrome (RLS). RLS is a disorder that causes a strong urge to move the legs. This ... may be a sign of infection, a blood disorder, or another ... may be a clue as to the cause of your anemia. In iron-deficiency anemia, for ...

  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

  7. Iron-Deficiency Anemia

    Medline Plus

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

  8. Iron-Deficiency Anemia

    Medline Plus

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

  9. Iron-Deficiency Anemia

    Medline Plus

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

  10. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... Frequent blood tests, especially in infants and small children Heavy menstrual periods Injury or surgery Urinary tract bleeding Consuming less than recommended daily amounts of iron Iron-deficiency anemia ... iron intake for children and adults. The table lists the recommended amounts ...

  11. Iron-Deficiency Anemia

    Medline Plus

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

  12. Iron-Deficiency Anemia

    Medline Plus

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

  13. Anemia - B12 deficiency

    Science.gov (United States)

    ... lack (deficiency) of vitamin B12 . Causes Your body needs vitamin B12 to make red blood cells. In order ... rest of your life. Some people may also need to take vitamin B12 supplements by mouth. Treatment may no longer ...

  14. Iron-Deficiency Anemia

    Medline Plus

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

  15. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... research and scientific discovery. Improving health with current research Learn about the following ways that NHLBI continues to translate ... Research Portfolio Online Reporting Tools (RePORT) to learn about research that NHLBI is funding on iron-deficiency anemia. ...

  16. Iron-Deficiency Anemia

    Medline Plus

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

  17. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... may be a sign of infection, a blood disorder, or another condition. Finally, the CBC looks at mean corpuscular (kor-PUS-kyu-lar) volume (MCV). MCV is a measure of the average size of your red blood cells. The results may be a clue as to the cause of your anemia. In iron-deficiency anemia, for ...

  18. Iron-Deficiency Anemia

    Medline Plus

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

  19. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... or advise you to eat more iron-rich foods. This not only will help you avoid iron-deficiency anemia, but also may lower your risk of having a low-birth-weight baby. Signs, Symptoms, and Complications The signs and ...

  20. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... may ask whether you might be pregnant. Physical Exam Your doctor will do a physical exam to look for signs of iron-deficiency anemia. ... liver and spleen Do a pelvic and rectal exam to check for internal bleeding Diagnostic Tests and ...

  1. Iron-Deficiency Anemia

    Medline Plus

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

  2. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... iron added). If you don't eat these foods regularly, or if you don't take an iron supplement, you're more likely to develop iron-deficiency anemia. Vegetarian diets can provide enough iron if you eat ...

  3. Iron-Deficiency Anemia

    Medline Plus

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

  4. Iron-Deficiency Anemia

    Medline Plus

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

  5. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... where there is blood loss during dialysis. People who have chronic kidney disease also often take other medicines—such as proton ... body. People with severe iron-deficiency anemia or who have chronic conditions such as kidney disease or celiac disease may be more likely to ...

  6. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... interferes with the body’s ability to make hemoglobin. Family history and genetics Von Willebrand disease is an ... clamping of your newborn’s umbilical cord at the time of delivery. This may help prevent iron-deficiency ...

  7. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... preventing, diagnosing, and treating heart, lung, blood, and sleep disorders. Are you a frequent blood donor living in New York City? This study is looking at how iron-deficiency anemia in blood donors affects the quality of donated red blood cells, such as how ...

  8. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... your doctor about delayed clamping of your newborn’s umbilical cord at the time of delivery. This may help ... Common symptoms of iron-deficiency anemia include: Chest pain Coldness in the hands and feet Difficulty concentrating ...

  9. Iron-Deficiency Anemia

    Medline Plus

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

  10. Iron-Deficiency Anemia

    Medline Plus

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

  11. Iron-Deficiency Anemia

    Medline Plus

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

  12. Iron-Deficiency Anemia

    Medline Plus

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

  13. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... and low-birth-weight babies (weighing less than 5.5 pounds) are at even greater risk for iron- ... loss during their monthly periods. About 1 in 5 women of childbearing age has iron-deficiency anemia. ...

  14. Iron-Deficiency Anemia

    Medline Plus

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

  15. 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...

  16. Genetics Home Reference: prolidase deficiency

    Science.gov (United States)

    ... instructions for making the enzyme prolidase, also called peptidase D. Prolidase helps divide certain dipeptides, which are ... Names for This Condition hyperimidodipeptiduria imidodipeptidase deficiency PD peptidase deficiency Related Information How are genetic conditions and ...

  17. ALPHA,·ANTITRYPSIN DEFICIENCY*

    African Journals Online (AJOL)

    1971-02-06

    Feb 6, 1971 ... Lieberman," in fact, found that 15·2% of 66 patients hospitalized with pulmonary emphysema had heterozygous alpha,-antitrypsin deficiency. The over-all incidence of the deficiency was 25'8% in this group. Of patients under the age of 50 years, 47·8% had deficient levels. If such observations are confirmed ...

  18. Iron deficiency and cognitive functions

    Directory of Open Access Journals (Sweden)

    Jáuregui-Lobera I

    2014-11-01

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

  19. [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.

  20. Deficiently extremal Gorenstein algebras

    Indian Academy of Sciences (India)

    Thus, R/I is a Cohen–. Macaulay algebra of Type 1, and hence R/I is Gorenstein. In view of Theorem 2.1, R/I is a nearly (or 1-deficient) extremal Gorenstein algebra. We now shall describe a result of Bruns and Hibi [1] which characterizes the Stanley–. Reisner rings having 2-pure but not 2-linear resolutions. Theorem 2.3.

  1. Iron deficiency anaemia

    OpenAIRE

    Barragán-Ibañez, G.; Santoyo-Sánchez, A.; Ramos-Peñafiel, C.O.

    2016-01-01

    Iron deficiency anaemia is a public health problem that affects all age groups. In Mexico, it is a common cause of morbidity, and accounts for 50% of cases of anaemia worldwide. It is more prevalent during the first 2 years of life, during adolescence and pregnancy. It is characterised by fatigue, weakness, pallor and koilonychia. Treatment is based on dietary recommendations and oral and intravenous iron supplements. In this review article, we summarise the characteristics of iron efficiency...

  2. Biotin and biotinidase deficiency

    OpenAIRE

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

    2008-01-01

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

  3. 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...

  4. Adenylosuccinate lyase deficiency.

    Science.gov (United States)

    Jurecka, Agnieszka; Zikanova, Marie; Kmoch, Stanislav; Tylki-Szymańska, Anna

    2015-03-01

    Adenylosuccinate lyase ADSL) deficiency is a defect of purine metabolism affecting purinosome assembly and reducing metabolite fluxes through purine de novo synthesis and purine nucleotide recycling pathways. Biochemically this defect manifests by the presence in the biologic fluids of two dephosphorylated substrates of ADSL enzyme: succinylaminoimidazole carboxamide riboside (SAICAr) and succinyladenosine (S-Ado). More than 80 individuals with ADSL deficiency have been identified, but incidence of the disease remains unknown. The disorder shows a wide spectrum of symptoms from slowly to rapidly progressing forms. The fatal neonatal form has onset from birth and presents with fatal neonatal encephalopathy with a lack of spontaneous movement, respiratory failure, and intractable seizures resulting in early death within the first weeks of life. Patients with type I (severe form) present with a purely neurologic clinical picture characterized by severe psychomotor retardation, microcephaly, early onset of seizures, and autistic features. A more slowly progressing form has also been described (type II, moderate or mild form), as having later onset, usually within the first years of life, slight to moderate psychomotor retardation and transient contact disturbances. Diagnosis is facilitated by demonstration of SAICAr and S-Ado in extracellular fluids such as plasma, cerebrospinal fluid and/or followed by genomic and/or cDNA sequencing and characterization of mutant proteins. Over 50 ADSL mutations have been identified and their effects on protein biogenesis, structural stability and activity as well as on purinosome assembly were characterized. To date there is no specific and effective therapy for ADSL deficiency.

  5. The prevalence of PI*S and PI*Z SERPINA1 alleles in healthy individuals and COPD patients in Saudi Arabia: A case-control study.

    Science.gov (United States)

    Al-Jameil, Noura; Hassan, Amina A; Hassanato, Rana; Isac, Sree R; Otaiby, Maram Al; Al-Shareef, Fadwa; Al-Maarik, Basmah; Ajeyan, Iman Al; Al-Bahloul, Khloud; Ghani, Samina; Al-Torbak, Dana

    2017-10-01

    Alpha-1 antitrypsin (AAT) is an acute phase protein produced in hepatocytes. Its deficiency affects the lungs and liver. A case-control study was carried out to determine the prevalence of 2 common deficiency alleles, PI*S and PI*Z, for alpha-1 antitrypsin deficiency (AATD) in both healthy and chronic obstructive pulmmonary disease (COPD)-affected Saudi populations and to clarify the importance of genetic tests in the screening of people at risk for COPD.One thousand blood samples from healthy individuals and 1000 from COPD-affected Saudi individuals were genotyped for the above-mentioned alleles, using real-time polymerase chain reaction (PCR), with the exclusion of any other nationalities. Data were analyzed by determining the allele and genotype frequencies through gene counting and its confidence intervals. The allele frequencies, derived by the Hardy-Weinberg equilibrium method, were analyzed by Pearson Chi-squared tests. The confidence intervals for genotype frequencies were calculated using exploratory software for confidence intervals.Of the 1000 COPD patients included in our study, the prevalence of PI*S and PI*Z was 21.8% and 7.7%, respectively, while within the 1000 normal samples, these alleles occurred in 8.9% of patients for PI*S and 1.6% for PI*Z. The AAT deficiency genotype frequencies (PI*ZZ, PI*SS, and PI*SZ) were 6.5 per 1000 and 87 per 1000 for normal and COPD-affected Saudi individuals.Our results indicated a high prevalence of AATD alleles in the normal Saudi population and an association between AAT deficiency and pulmonary disease development. Additionally, our research confirms the importance of genetic screening to achieve early and accurate diagnosis of AATD.

  6. Protein misfolding and degradation in genetic diseases

    DEFF Research Database (Denmark)

    Bross, P; Corydon, T J; Andresen, B S

    1999-01-01

    to accumulation of protein aggregates that damage the cell. Mechanisms by which misfolded proteins are selected for degradation have first been delineated for the endoplasmatic reticulum; this process has been termed "protein quality control." Similar mechanisms appear to be operative in all cellular compartments......Investigations of genetic diseases such as cystic fibrosis, alpha-1-antitrypsin deficiency, phenylketonuria, mitochondrial acyl-CoA dehydrogenase deficiencies, and many others have shown that enhanced proteolytic degradation of mutant proteins is a common molecular pathological mechanism. Detailed...... studies of the fate of mutant proteins in some of these diseases have revealed that impaired or aberrant folding of mutant polypeptides typically results in prolonged interaction with molecular chaperones and degradation by intracellular proteases before the functional conformation is acquired...

  7. [Production of human proteins in the blood of transgenic animals

    NARCIS (Netherlands)

    Massoud, M.; Bischoff, Rainer; Dalemans, W.; Pointu, H.; Attal, J.; Schultz, H.; Clesse, D.; Stinnakre, M.G.; Pavirani, A.; Houdebine, L.M.

    1990-01-01

    The human alpha 1-antitrypsin gene has been microinjected into rabbit embryos. A line of transgenic rabbits has thus been established. Human alpha 1-antitrypsin was found in the blood of transgenic animals at the concentration of 1 mg/ml plasma. The human protein was active and separable from its

  8. Novel Therapeutic and Prophylactic Modalities to Protect the United States Armed Forces Against Mayor Biological Threat Agents

    Science.gov (United States)

    2007-08-01

    fact that GSK-3β is a specific substrate of AKT kinase activity, that the downstream activity of GSK-3β regulating glycogenolysis by liver and...Br J Haematol 2000, 109(2):342-348. 102 Janciauskiene S, Nita I, Stevens T: Alpha1-antitrypsin, old dog , new tricks. Alpha1-antitrypsin exerts in

  9. Primary Carnitine Deficiency

    DEFF Research Database (Denmark)

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

    2017-01-01

    Primary carnitine deficiency (PCD) causes low levels of carnitine in patients potentially leading to metabolic and cardiac symptoms. Newborn screening for PCD is now routine in many countries by measuring carnitine levels in infants. In this study we report Apgar scores, length and weight...... in newborns with PCD and newborns born to mothers with PCD compared to controls. Furthermore we report how effective different screening algorithms have been to detect newborns with PCD in the Faroe Islands. RESULTS: Newborns with PCD and newborns born to mothers with PCD did not differ with regard to Apgar...

  10. Pseudoachondroplasia with immune deficiency

    International Nuclear Information System (INIS)

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

    1988-01-01

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

  11. Morbidity and GH deficiency

    DEFF Research Database (Denmark)

    Stochholm, Kirstine; Laursen, Torben; Green, Anders

    2008-01-01

    identified in the National Patient Registry. Lag time until first admission was used as a measure of morbidity. Patients were divided into childhood onset (CO) and adult onset (AO), discriminated by an age cut-off of 18 years at onset of GHD. METHOD: Sex- and cause-specific hazard ratios (HRs) in CO and AO......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...

  12. Iron deficiency anaemia

    Directory of Open Access Journals (Sweden)

    G. Barragán-Ibañez

    2016-04-01

    Full Text Available Iron deficiency anaemia is a public health problem that affects all age groups. In Mexico, it is a common cause of morbidity, and accounts for 50% of cases of anaemia worldwide. It is more prevalent during the first 2 years of life, during adolescence and pregnancy. It is characterised by fatigue, weakness, pallor and koilonychia. Treatment is based on dietary recommendations and oral and intravenous iron supplements. In this review article, we summarise the characteristics of iron efficiency anaemia, its metabolism, epidemiology, symptoms and diagnosis, and explore different therapeutic approaches.

  13. Orexin deficiency and narcolepsy.

    Science.gov (United States)

    Sakurai, Takeshi

    2013-10-01

    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 therapies targeting the orexin system for sleep disorders including insomia and narcolepsy-cataplexy. Copyright © 2013 Elsevier Ltd. All rights reserved.

  14. 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...... in CO and AO GHD in both genders, when compared with controls. The hazard ratio (HR) for CO males was 8.3 (95% confidence interval (CI) 4.5-15.1) and for females 9.4 (CI 4.6-19.4). For AO males, HR was 1.9 (CI 1.7-2.2) and for females 3.4 (CI 2.9-4.0). We found a significantly higher HR in AO females...... a significantly increased mortality in GHD patients when compared with controls, possibly due to their hypopituitary status. Mortality was increased in AO female patients when compared with males. For CO and AO GHD, different causes of significantly increased mortality were identified...

  15. Vitamin A deficiency disorders.

    Science.gov (United States)

    McLaren, D S

    1999-08-01

    The major cause of blindness in children worldwide is xerophthalmia caused by vitamin A deficiency. In addition it has other adverse effects, including increased mortality and the term vitamin A deficiency disorders (VADD) has been introduced to cover the whole clinical spectrum of disease. The ocular manifestations of xerophthalmia have been classified and a set of prevalence criteria for the detection of a problem of public health magnitude has been in use for more than two decades. The global prevalence of VADD is now well documented and World Health Organisation (WHO) receives information continuously for updating its data base on the subject. The pathogenesis of the disease is still imperfectly understood, it is not at all clear precisely why certain subjects in vulnerable communities develop xerophthalmia, while the majority are spared. A schedule for treatment of the established case has been available for a long time, but at both clinic and hospital level concentrated sources of vitamin A for treatment are frequently not available. More emphasis needs to be laid on prevention and a choice of methods consisting of large dose supplementation, fortification of food, control of precipitating infections and dietary improvement. The advantages and drawbacks of each are discussed.

  16. Lead toxicity and nutritional deficiencies

    Energy Technology Data Exchange (ETDEWEB)

    Levander, O.A.

    1979-04-01

    Recent data concerning lead toxicity and nutritional deficiencies are summarized. Lead poisoning can be exacerbated by consumption of either deficient or excessive levels of protein. Mineral deficiencies also exaggerate lead poisoning. Evidence for antagonism between lead and nutritional levels of selenium is inconclusive. Vitamin E deficiency and lead poisoning interact to produce an anemia in rats that is more severe than that caused by either treatment alone. A pro-oxidant stress of lead on red blood cells is hypothesized to cause their accelerated destruction. In addition, disruption of normal membrane structure, leading to peroxidative damage, may occur. Calcium deficiencies in children are negatively correlated with lead concentrations in their blood. Other examples of interactions between minerals and lead poisoning are provided. Nutritional deficiencies have been shown to have an additive effect in potentiating lead toxicity in some cases. (112 references, 4 tables)

  17. 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

  18. 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

  19. Iron Deficiency and Bariatric Surgery

    OpenAIRE

    J?uregui-Lobera, Ignacio

    2013-01-01

    It is estimated that the prevalence of anaemia in patients scheduled for bariatric surgery is higher than in the general population and the prevalence of iron deficiencies (with or without anaemia) may be higher as well. After surgery, iron deficiencies and anaemia may occur in a higher percentage of patients, mainly as a consequence of nutrient deficiencies. In addition, perioperative anaemia has been related with increased postoperative morbidity and mortality and poorer quality of life aft...

  20. [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.

  1. Genetics Home Reference: transcobalamin deficiency

    Science.gov (United States)

    ... Deficiency Patient Support and Advocacy Resources (3 links) American Association on Intellectual and Developmental Disabilities (AAIDD) CLIMB: Children Living with Inherited Metabolic Diseases ( ...

  2. 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.

  3. Argininosuccinate lyase deficiency.

    Science.gov (United States)

    Nagamani, Sandesh C S; Erez, Ayelet; Lee, Brendan

    2012-05-01

    The urea cycle consists of six consecutive enzymatic reactions that convert waste nitrogen into urea. Deficiencies of any of these enzymes of the cycle result in urea cycle disorders (UCDs), a group of inborn errors of hepatic metabolism that often result in life-threatening hyperammonemia. Argininosuccinate lyase (ASL) catalyzes the fourth reaction in this cycle, resulting in the breakdown of argininosuccinic acid to arginine and fumarate. ASL deficiency (ASLD) is the second most common UCD, with a prevalence of ~1 in 70,000 live births. ASLD can manifest as either a severe neonatal-onset form with hyperammonemia within the first few days after birth or as a late-onset form with episodic hyperammonemia and/or long-term complications that include liver dysfunction, neurocognitive deficits, and hypertension. These long-term complications can occur in the absence of hyperammonemic episodes, implying that ASL has functions outside of its role in ureagenesis and the tissue-specific lack of ASL may be responsible for these manifestations. The biochemical diagnosis of ASLD is typically established with elevation of plasma citrulline together with elevated argininosuccinic acid in the plasma or urine. Molecular genetic testing of ASL and assay of ASL enzyme activity are helpful when the biochemical findings are equivocal. However, there is no correlation between the genotype or enzyme activity and clinical outcome. Treatment of acute metabolic decompensations with hyperammonemia involves discontinuing oral protein intake, supplementing oral intake with intravenous lipids and/or glucose, and use of intravenous arginine and nitrogen-scavenging therapy. Dietary restriction of protein and dietary supplementation with arginine are the mainstays in long-term management. Orthotopic liver transplantation (OLT) is best considered only in patients with recurrent hyperammonemia or metabolic decompensations resistant to conventional medical therapy.

  4. Adeno-associated virus-based gene therapy for inherited disorders.

    Science.gov (United States)

    Flotte, Terence R

    2005-12-01

    Adeno-associated virus vectors are capable of long-term gene transfer without obvious adverse effects in a number of animal models. Over the last two decades, preclinical and early phase clinical trials in cystic fibrosis and alpha-1 antitrypsin deficiency were undertaken to test the feasibility of this approach. The results of those studies have been important since they have indicated that in vivo gene transfer is feasible and relatively safe. In addition, a number of key limitations to the current generation of AAV2 gene therapy vectors have been defined. The information about these limitations has been used to develop newer AAV vector approaches, based on new mutant and alternative serotype capsids and enhanced promoter systems. The evaluation of safety and efficacy of these newer agents is ongoing.

  5. Accuracy of preimplantation genetic diagnosis (PGD) of single gene and chromosomal disorders

    Energy Technology Data Exchange (ETDEWEB)

    Verlinsky, Y.; Strom, C.; Rechitsky, S. [Reproductive Genetics Institute, Chicage, IL (United States)] [and others

    1994-09-01

    We have developed a polar body inferred approach for preconception diagnosis of single gene and chromosomal disorders. Preconception PCR or FISH analysis was performed in a total of 310 first polar bodies for the following genetic conditions: cystic fibrosis, hemophilia A, alpha-1-antitrypsin deficiency, Tay Sachs disease, retinitis pigmentosa and common chromosomal trisomies. An important advantage of this approach is the avoidance of sperm (DNA) contamination, which is the major problem of PGD. We are currently applying FISH analysis of biopsied blastomeres, in combination with PCR or separately, and have demonstrated a significant improvement of the accuracy of PGD of X-linked disorders at this stage. Our data have also demonstrated feasibility of the application of FISH technique for PGD of chromosomal disorders. It was possible to detect chromosomal non-disjunctions and chromatid malsegregations in the first meiotic division, as well as to evaluate chromosomal mutations originating from the second meiotic nondisjunction.

  6. Progression of emphysema in a 12-month hyperpolarized 3He-MRI study: lacunarity analysis provided a more sensitive measure than standard ADC analysis

    DEFF Research Database (Denmark)

    Diaz, Sandra; Casselbrant, Ingrid; Piitulainen, Eeva

    2009-01-01

    RATIONALE AND OBJECTIVES: Inhaled hyperpolarized (3)He magnetic resonance (MR) imaging has been used to measure alveolar size in patients with emphysema. The aim of this study was to test the hypothesis that (3)He MR images could be used to develop a biomarker of emphysema progression. MATERIALS...... AND METHODS: Twelve healthy controls and 18 patients with emphysema (eight current smokers, 10 ex-smokers) were imaged at baseline and 6 and 12 months. An additional nine subjects with alpha-1 antitrypsin deficiency (four with emphysema, six without symptoms) were also imaged at baseline and at 6 months. Each...... subject was imaged at two lung volumes: functional residual capacity (FRC) and FRC plus 15% of total lung capacity. Means and standard deviations of apparent diffusion coefficients (ADCs) were calculated from coronal images of the entire lung and correlated with pulmonary function test results...

  7. Long-range correlations of serial FEV1 measurements in emphysematous patients and normal subjects

    DEFF Research Database (Denmark)

    Dirksen, A; Holstein-Rathlou, N H; Madsen, F

    1998-01-01

    are autocorrelated. The purpose of this study was to describe the correlation structure in time series of FEV1 measurements. Nineteen patients with severe alpha1-antitrypsin deficiency (phenotype PiZ) and moderate to severe emphysema and two subjects with normal lungs were followed for several years with daily self...... patients was approximately 0.35 for short intervals and decreased almost exponentially with a half time of 38 days. Between 3 and 4 mo, the autocorrelation function became negative. It reached a minimum of -0.1 at approximately 8 mo and then increased toward zero over the following 12 mo....... The autocorrelation function in the two normal subjects showed a similar pattern, but with a faster decay toward zero. In the patients, the power spectrum had a peak at 1 cycle/wk and showed a 1/f pattern, where f is frequency, with a slope of -0.88 at lower frequencies. We conclude that serial spirometric...

  8. Long-range correlations of serial FEV1 measurements in emphysematous patients and normal subjects

    DEFF Research Database (Denmark)

    Dirksen, A; Holstein-Rathlou, N H; Madsen, F

    1998-01-01

    are autocorrelated. The purpose of this study was to describe the correlation structure in time series of FEV1 measurements. Nineteen patients with severe alpha1-antitrypsin deficiency (phenotype PiZ) and moderate to severe emphysema and two subjects with normal lungs were followed for several years with daily self...... patients was approximately 0.35 for short intervals and decreased almost exponentially with a half time of 38 days. Between 3 and 4 mo, the autocorrelation function became negative. It reached a minimum of -0.1 at approximately 8 mo and then increased toward zero over the following 12 mo...... measurements show long-range correlations. The practical implication is that FEV1 need not be measured more often than once every 3 mo in studies of the long-term trends in lung function....

  9. Diagnosis, assessment, and phenotyping of COPD

    DEFF Research Database (Denmark)

    Lange, Peter; Halpin, David M; O'Donnell, Denis E

    2016-01-01

    COPD is now widely recognized as a complex heterogeneous syndrome, having both pulmonary and extrapulmonary features. In clinical practice, the diagnosis of COPD is based on the presence of chronic airflow limitation, as assessed by post-bronchodilator spirometry. The severity of the airflow...... limitation, as measured by percent predicted FEV1, provides important information to the physician to enable optimization of management. However, in order to accurately assess the complexity of COPD, there need to be other measures made beyond FEV1. At present, there is a lack of reliable and simple blood...... biomarkers to confirm and further assess the diagnosis of COPD. However, it is possible to identify patients who display different phenotypic characteristics of COPD that relate to clinically relevant outcomes. Currently, validated phenotypes of COPD include alpha-1 antitrypsin deficiency, and "frequent...

  10. Alpha-1 couples: interpersonal and intrapersonal predictors of spousal communication and stress.

    Science.gov (United States)

    Smith, Rachel A; Wienke, Sara; Coffman, Donna L

    2014-04-01

    Couples often discuss genetic test results, and then manage their implications together. This interdependence can lead to common, shared experiences, similar intrapersonal processes to manage shared stressors, or interpersonal influences between spouses, leading to different outcomes. This study sought to reveal the intracouple, intrapersonal, and interpersonal influences of genetic stigma and negative feelings on spousal communication and perceived stress with 50 couples in which one spouse is a member of a genetic disease registry. The results were analyzed with dyadic analysis, including multilevel modeling. The findings showed that registered members and their spouses were not statistically different in their mean levels of perceived genetic stigma, negative feelings about alpha-1 antitrypsin deficiency (AATD), conversations with each other about the AATD test results, and their perceived stress. The findings also showed that their intracouple consistencies were not high, and their intrapersonal and interpersonal influences on communication and stress differed. The social implications of genetic research at the interpersonal level are discussed.

  11. [Frederic Chopin (1810-1849), and his disease].

    Science.gov (United States)

    Young, Pablo; Bernaciak, Jorge M; Bruetman, Julio E; Finn, Bárbara C; Miranda, Marcelo C

    2014-04-01

    Frédéric Chopin - a great Polish composer and pianist-suffered from a chronic disease. Both during his life and after his death, physicians disagreed on Chopin's diagnosis. His contemporaries accepted the diagnosis of tuberculosis, a common disease in the 18th century. Description of new clinical entities provoked new dilemmas in the 21th century. Although other alternative diagnoses to tuberculosis have emerged, such as cystic fibrosis or alpha-1 antitrypsin deficiency, we still sustain that the first diagnosis is the most probable. In this paper we report F. Chopin's case history and discuss cons and pros for different diseases as the cause of F. Chopin's suffering and death.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1991-03-15

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

  13. Genetics Home Reference: dopamine transporter deficiency syndrome

    Science.gov (United States)

    ... Twitter Home Health Conditions Dopamine transporter deficiency syndrome Dopamine transporter deficiency syndrome Printable PDF Open All Close ... Javascript to view the expand/collapse boxes. Description Dopamine transporter deficiency syndrome is a rare movement disorder. ...

  14. Genetics Home Reference: lactate dehydrogenase deficiency

    Science.gov (United States)

    ... this condition: lactate dehydrogenase-A deficiency (sometimes called glycogen storage disease XI) and lactate dehydrogenase-B deficiency. People with ... Resources Genetic Testing (2 links) Genetic Testing Registry: Glycogen storage disease XI Genetic Testing Registry: Lactate dehydrogenase B deficiency ...

  15. Monocular Elevation Deficiency - Double Elevator Palsy

    Science.gov (United States)

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

  16. Activation of proteinase 3 contributes to Non-alcoholic Fatty Liver Disease (NAFLD) and insulin resistance.

    Science.gov (United States)

    Toonen, Erik J M; Mirea, Andreea-Manuela; Tack, Cees J; Stienstra, Rinke; Ballak, Dov B; van Diepen, Janna A; Hijmans, Anneke; Chavakis, Triantafyllos; Dokter, Wim H; Pham, Christine T N; Netea, Mihai G; Dinarello, Charles A; Joosten, Leo A B

    2016-05-24

    Activation of inflammatory pathways is known to accompany development of obesity-induced non-alcoholic fatty liver disease (NAFLD), insulin resistance and type 2 diabetes. In addition to caspase-1, the neutrophil serine proteases proteinase 3, neutrophil elastase and cathepsin G are able to process the inactive pro-inflammatory mediators IL-1β and IL-18 to their bioactive forms, thereby regulating inflammatory responses. In the present study, we investigated whether proteinase 3 is involved in obesity-induced development of insulin resistance and NAFLD. We investigated the development of NAFLD and insulin resistance in mice deficient for neutrophil elastase/proteinase 3 and neutrophil elastase/cathepsin G and in wild-type mice treated with the neutrophil serine proteinase inhibitor human alpha-1 antitrypsin. Expression profiling of metabolically relevant tissues obtained from insulin resistant mice showed that expression of proteinase 3 was specifically upregulated in the liver, whereas neutrophil elastase, cathepsin G and caspase-1 were not. Neutrophil elastase/proteinase 3 deficient mice showed strongly reduced levels of lipids in the liver after fed a high fat diet. Moreover, these mice were resistant to high fat diet-induced weight gain, inflammation and insulin resistance. Injection of proteinase 3 exacerbated insulin resistance in caspase-1(-/-) mice, indicating that proteinase 3 acts independently of caspase-1. Treatment with alpha-1 antitrypsin during the last 10 days of a 16 week high fat diet reduced hepatic lipid content and decreased fasting glucose levels. We conclude that proteinase 3 is involved in NAFLD and insulin resistance and that inhibition of proteinase 3 may have therapeutic potential.

  17. Iron deficiency - a global problem

    International Nuclear Information System (INIS)

    Ali, S.M.

    1993-01-01

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

  18. Pagophagia in iron deficiency anemia.

    Science.gov (United States)

    Uchida, Tatsumi; Kawati, Yasunori

    2014-04-01

    The relationship between pagophagia (ice pica) and iron deficiency anemia was studied. All 81 patients with iron deficiency anemia defined as hemoglobin Pagophagia was defined as compulsive and repeated ingestion of at least one tray of ice or ice eating which was relieved after iron administration. Pagophagia was present in 13 patients (16.0%). All patients who received oral iron were periodically assessed employing a questionnaire on pagophagia and laboratory data. Iron therapy can cure the pagophagia earlier than hemoglobin recovery and repair of tissue iron deficiency. Although the pathogenesis of pagophagia is unclear, a biochemical approach involving the central nervous system might elucidate the mechanism underlying these abnormal behaviors.

  19. Iron deficiency among blood donors

    DEFF Research Database (Denmark)

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

    2017-01-01

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

  20. Evolutionary Processes and Mental Deficiency

    Science.gov (United States)

    Spitz, Herman H.

    1973-01-01

    The author hypothesizes that central nervous system damage of deficiency associated with mental retardation affects primarily those cortical processes which developed at a late stage in man's evolutionary history. (Author)

  1. Selective IgA Deficiency

    OpenAIRE

    Yel, Leman

    2010-01-01

    Introduction: Immunoglobulin A (IgA) deficiency is the most common primary immunodeficiency defined as decreased serum level of IgA in the presence of normal levels of other immunoglobulin isotypes. Most individuals with IgA deficiency are asymptomatic and identified coincidentally. However, some patients may present with recurrent infections of the respiratory and gastrointestinal tracts, allergic disorders, and autoimmune manifestations. IgA and Its Functions: Although IgA is the most abund...

  2. Iron deficiency and cognitive functions

    OpenAIRE

    Jáuregui-Lobera, Ignacio

    2014-01-01

    Ignacio Jáuregui-Lobera Department of Nutrition and Bromatology, Pablo de Olavide University, Seville, Spain Abstract: Micronutrient deficiencies, especially those related to iodine and iron, are linked to different cognitive impairments, as well as to potential long-term behavioral changes. Among the cognitive impairments caused by iron deficiency, those referring to attention span, intelligence, and sensory perception functions are mainly cited, as well as those associated with...

  3. Iron-Deficiency Anemia (For Parents)

    Science.gov (United States)

    ... Staying Safe Videos for Educators Search English Español Iron-Deficiency Anemia KidsHealth / For Parents / Iron-Deficiency Anemia ... anemia, a common nutritional deficiency in children. About Iron-Deficiency Anemia Every red blood cell in the ...

  4. Iron deficiency and bariatric surgery.

    Science.gov (United States)

    Jáuregui-Lobera, Ignacio

    2013-05-15

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

  5. Iron Deficiency and Bariatric Surgery

    Directory of Open Access Journals (Sweden)

    Ignacio Jáuregui-Lobera

    2013-05-01

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

  6. Leaf Senescence by Magnesium Deficiency

    Directory of Open Access Journals (Sweden)

    Keitaro Tanoi

    2015-12-01

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

  7. 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

  8. [Nutritional deficiencies associated with bariatric surgery].

    Science.gov (United States)

    Folope, Vanessa; Coëffier, Moïse; Déchelotte, Pierre

    2007-04-01

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

  9. 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.

  10. Preventing Iron Deficiency and Anaemia

    African Journals Online (AJOL)

    Siegal_D

    Anaemia, often due to iron deficiency, is one of the most widespread causes of mortality and morbidity in ... Pregnant women must make many new red blood cells, provide iron for the foetus and may lose much blood during .... Do not give tea and coffee to children. • Eat fermented porridges and germinate/malt cereals and ...

  11. 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 existi...

  12. Genetics Home Reference: proopiomelanocortin deficiency

    Science.gov (United States)

    ... individuals are prone to weight-related conditions like cardiovascular disease or type 2 diabetes . Low levels of ACTH ... to run in my family? What is the prognosis of a genetic condition? Genetic and Rare Diseases Information Center Frequency POMC deficiency is a rare ...

  13. Iron deficiency anemia in children

    Directory of Open Access Journals (Sweden)

    Pochinok T.V.

    2016-05-01

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

  14. 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

  15. Iron deficiency in cancer patients

    Directory of Open Access Journals (Sweden)

    Flávio Augusto Naoum

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

  16. 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

  17. 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...

  18. Iron refractory iron deficiency anemia

    Science.gov (United States)

    De Falco, Luigia; Sanchez, Mayka; Silvestri, Laura; Kannengiesser, Caroline; Muckenthaler, Martina U.; Iolascon, Achille; Gouya, Laurent; Camaschella, Clara; Beaumont, Carole

    2013-01-01

    Iron refractory iron deficiency anemia is a hereditary recessive anemia due to a defect in the TMPRSS6 gene encoding Matriptase-2. This protein is a transmembrane serine protease that plays an essential role in down-regulating hepcidin, the key regulator of iron homeostasis. Hallmarks of this disease are microcytic hypochromic anemia, low transferrin saturation and normal/high serum hepcidin values. The anemia appears in the post-natal period, although in some cases it is only diagnosed in adulthood. The disease is refractory to oral iron treatment but shows a slow response to intravenous iron injections and partial correction of the anemia. To date, 40 different Matriptase-2 mutations have been reported, affecting all the functional domains of the large ectodomain of the protein. In vitro experiments on transfected cells suggest that Matriptase-2 cleaves Hemojuvelin, a major regulator of hepcidin expression and that this function is altered in this genetic form of anemia. In contrast to the low/undetectable hepcidin levels observed in acquired iron deficiency, in patients with Matriptase-2 deficiency, serum hepcidin is inappropriately high for the low iron status and accounts for the absent/delayed response to oral iron treatment. A challenge for the clinicians and pediatricians is the recognition of the disorder among iron deficiency and other microcytic anemias commonly found in pediatric patients. The current treatment of iron refractory iron deficiency anemia is based on parenteral iron administration; in the future, manipulation of the hepcidin pathway with the aim of suppressing it might become an alternative therapeutic approach. PMID:23729726

  19. 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 ...

  20. Genetics Home Reference: leptin receptor deficiency

    Science.gov (United States)

    ... People with leptin receptor deficiency also have hypogonadotropic hypogonadism, which is a condition caused by reduced production ... weight gain associated with this disorder. Because hypogonadotropic hypogonadism occurs in leptin receptor deficiency , researchers suggest that ...

  1. Genetics Home Reference: isolated growth hormone deficiency

    Science.gov (United States)

    ... cells that help protect the body against infection (agammaglobulinemia). Related Information What does it mean if a ... deficiency type 1B Genetic Testing Registry: X-linked agammaglobulinemia with growth hormone deficiency Other Diagnosis and Management ...

  2. Genetics Home Reference: complement component 2 deficiency

    Science.gov (United States)

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

  3. Genetics Home Reference: IRAK-4 deficiency

    Science.gov (United States)

    ... Encyclopedia: Septicemia Health Topic: Immune System and Disorders Genetic and Rare Diseases Information Center (1 link) IRAK-4 deficiency Additional NIH Resources (1 link) National Institute of Allergy and Infectious Diseases: Primary Immune Deficiency Diseases Educational Resources (2 ...

  4. Genetics Home Reference: congenital leptin deficiency

    Science.gov (United States)

    ... Description Congenital leptin deficiency is a condition that causes severe obesity beginning in the first few months of life. ... are unknown. Congenital leptin deficiency is a rare cause of obesity. Researchers are studying the factors involved in more ...

  5. Genetics Home Reference: pyruvate carboxylase deficiency

    Science.gov (United States)

    ... condition has been reported mostly in Europe, particularly France. Affected infants have severe lactic acidosis, a buildup ... Pyruvate carboxylase deficiency MalaCards: pyruvate carboxylase deficiency Merck Manual Consumer Version: Overview of Hereditary Metabolic Disorders Orphanet: ...

  6. Genetics Home Reference: dihydropyrimidine dehydrogenase deficiency

    Science.gov (United States)

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

  7. 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

  8. G6PD Deficiency in Turkish Cypriots

    OpenAIRE

    SÖZÜÖZ, Ayşe

    2014-01-01

    1108 Turkish Cypriot men and 318 male labourers from mainland Turkey were screened for G6PD deficiency and haemoglobinopathy traits. The results revealed a 6.7% G6PD deficiency rate in the Turkish Cypriot men and a 1.6% prevalance rate in the Turkish men. The mean haemoglobin level of the G6PD deficient males was approximately 1g/dl lower than that of the non-deficient males.

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

    African Journals Online (AJOL)

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

  10. Galactose Epimerase Deficiency: Expanding the Phenotype

    NARCIS (Netherlands)

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

    2017-01-01

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

  11. DNA repair deficiency in neurodegeneration

    DEFF Research Database (Denmark)

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

    2011-01-01

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

  12. 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.

  13. Vitamin D deficiency in Fibromyalgia

    International Nuclear Information System (INIS)

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

    2010-01-01

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

  14. Metabolic surgery and nutritional deficiencies.

    Science.gov (United States)

    Stroh, Christine; Manger, Thomas; Benedix, Frank

    2017-10-01

    The increasing prevalence of morbid obesity in Germany is associated with an increasing number of metabolic surgical interventions. Short-term surgical and long-term metabolic complications such as nutrient deficiencies can be considered as the main risks of metabolic surgery with its malabsorptive but also restrictive procedures. The aim of this review was to characterize the most relevant metabolic complications specific for the various bariatric procedures, which, subsequently, require a permanent surveillance and supplementation, respectively. Furthermore, we aimed to identify if there are diagnostic and therapeutic measures that can prevent those complications. Restrictive bariatric surgery such as "gastric banding" and "sleeve gastrectomy" can be associated with deficiencies related to B-vitamins whereas iron, folate, vitamin B1, B12 and D deficiencies are associated with the malabsorptive procedure such as "biliopancreatic diversion," "duodenal switch" and "Roux-en-Y gastric bypass". Due to possible metabolic and surgical complications after bariatric surgery, patients need to undergo life-long medical and dietetic surveillance. The recently published guidelines of the "American Association of Bariatric and Metabolic Surgery" are the basis for recommendations on supplementation and treatment following weight loss surgery.

  15. Nutritional Deficiencies and Phospholipid Metabolism

    Directory of Open Access Journals (Sweden)

    Nidia N. Gomez

    2011-04-01

    Full Text Available Phospholipids are important components of the cell membranes of all living species. They contribute to the physicochemical properties of the membrane and thus influence the conformation and function of membrane-bound proteins, such as receptors, ion channels, and transporters and also influence cell function by serving as precursors for prostaglandins and other signaling molecules and modulating gene expression through the transcription activation. The components of the diet are determinant for cell functionality. In this review, the effects of macro and micronutrients deficiency on the quality, quantity and metabolism of different phospholipids and their distribution in cells of different organs is presented. Alterations in the amount of both saturated and polyunsaturated fatty acids, vitamins A, E and folate, and other micronutrients, such as zinc and magnesium, are discussed. In all cases we observe alterations in the pattern of phospholipids, the more affected ones being phosphatidylcholine, phosphatidylethanolamine and sphingomyelin. The deficiency of certain nutrients, such as essential fatty acids, fat-soluble vitamins and some metals may contribute to a variety of diseases that can be irreversible even after replacement with normal amount of the nutrients. Usually, the sequelae are more important when the deficiency is present at an early age.

  16. Flu Vaccine Guidance for Patients with Immune Deficiency

    Science.gov (United States)

    ... Guidance for Patients with Immune Deficiency Share | Flu Vaccine Guidance for Patients with Immune Deficiency This article ... should patients with immune deficiency be given the vaccine? Immune deficient patients have a decreased resistance to ...

  17. 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...

  18. 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.

  19. Nutrient deficiencies prior to bariatric surgery.

    Science.gov (United States)

    Roust, Lori R; DiBaise, John K

    2017-03-01

    The purpose of this review is to provide an update of recent additions to our understanding of the prevalence of nutrient deficiencies and the potential role of preoperative weight loss in contributing to these deficiencies in obese individuals planning to undergo bariatric surgery. Recent reports that have included bariatric surgery candidates from sites around the world have shown consistent deficiencies in a variety of nutrients. Although protein-energy malnutrition is uncommon preoperatively, micronutrient deficiencies occur commonly with multiple deficiencies often present in the same individual. No difference in the prevalence of deficiency between men and women is apparent, and a standard profile of susceptibility to deficiency has not been identified. In the only studies that have evaluated dietary intake of total energy, macronutrients and micronutrients preoperatively, despite an excess of calories ingested, micronutrient intake tends to be lower than recommended. A high prevalence of micronutrient deficiencies, especially vitamin D, folate, B12 and iron, is present in obese individuals being considered for bariatric surgery. Despite high-caloric intake, the deficiencies present appear to be related to the poor quality of the diet and low micronutrient intake. These findings strengthen prior recommendations of routine preoperative nutritional screening. Because a standard profile of susceptibility to deficiency has not been identified, extensive nutritional screening, including micronutrient testing, should be considered in all patients in the preoperative setting. Finally, we recommend early supplementation of vitamins and minerals based on laboratory assessment and incorporation of a program to optimize eating behaviors prior to surgery.

  20. Organophosphate exposure with pseudocholinesterase deficiency.

    Science.gov (United States)

    Lurati, Ann R

    2013-06-01

    A 36-year-old correctional officer was exposed to lice while at work and self-treated with chlorpyrifos, an organophosphate. The correctional officer applied chlorpyrifos to her entire body and did not wash it off for 8 to 12 hours. Eight hours after the initial application, the correctional officer developed abdominal cramps, diarrhea, sweating, excessive salivation, frequent urination, and increased bronchial secretions. After a phone consultation with the occupational health clinic, the correctional officer reported to the emergency department, was diagnosed with organophosphate toxicity, and was treated with atropine. Later testing revealed that the correctional officer had pseudocholinesterase deficiency. Copyright 2013, SLACK Incorporated.

  1. 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...

  2. CK (Creatine Kinase) Test

    Science.gov (United States)

    ... Blood Testing Alpha-1 Antitrypsin Alpha-fetoprotein (AFP) Tumor Marker AMAS Aminoglycoside Antibiotics Ammonia Amniocentesis Amylase ANCA/MPO/ ... Beta-2 Microglobulin Kidney Disease Beta-2 Microglobulin Tumor Marker Bicarbonate (Total CO2) Bilirubin Blood Culture Blood Gases ...

  3. Myasthenia Gravis Tests

    Science.gov (United States)

    ... Blood Testing Alpha-1 Antitrypsin Alpha-fetoprotein (AFP) Tumor Marker AMAS Aminoglycoside Antibiotics Ammonia Amniocentesis Amylase ANCA/MPO/ ... Beta-2 Microglobulin Kidney Disease Beta-2 Microglobulin Tumor Marker Bicarbonate (Total CO2) Bilirubin Blood Culture Blood Gases ...

  4. HIV Genotypic Resistance Testing

    Science.gov (United States)

    ... Blood Testing Alpha-1 Antitrypsin Alpha-fetoprotein (AFP) Tumor Marker AMAS Aminoglycoside Antibiotics Ammonia Amniocentesis Amylase ANCA/MPO/ ... Beta-2 Microglobulin Kidney Disease Beta-2 Microglobulin Tumor Marker Bicarbonate (Total CO2) Bilirubin Blood Culture Blood Gases ...

  5. With Home Testing, Consumers Take Charge of Their Health

    Science.gov (United States)

    ... Blood Testing Alpha-1 Antitrypsin Alpha-fetoprotein (AFP) Tumor Marker AMAS Aminoglycoside Antibiotics Ammonia Amniocentesis Amylase ANCA/MPO/ ... Beta-2 Microglobulin Kidney Disease Beta-2 Microglobulin Tumor Marker Bicarbonate (Total CO2) Bilirubin Blood Culture Blood Gases ...

  6. Liver Panel

    Science.gov (United States)

    ... Blood Testing Alpha-1 Antitrypsin Alpha-fetoprotein (AFP) Tumor Marker AMAS Aminoglycoside Antibiotics Ammonia Amniocentesis Amylase ANCA/MPO/ ... Beta-2 Microglobulin Kidney Disease Beta-2 Microglobulin Tumor Marker Bicarbonate (Total CO2) Bilirubin Blood Culture Blood Gases ...

  7. Mono Test

    Science.gov (United States)

    ... Blood Testing Alpha-1 Antitrypsin Alpha-fetoprotein (AFP) Tumor Marker AMAS Aminoglycoside Antibiotics Ammonia Amniocentesis Amylase ANCA/MPO/ ... Beta-2 Microglobulin Kidney Disease Beta-2 Microglobulin Tumor Marker Bicarbonate (Total CO2) Bilirubin Blood Culture Blood Gases ...

  8. Pleural Fluid Analysis Test

    Science.gov (United States)

    ... Blood Testing Alpha-1 Antitrypsin Alpha-fetoprotein (AFP) Tumor Marker AMAS Aminoglycoside Antibiotics Ammonia Amniocentesis Amylase ANCA/MPO/ ... Beta-2 Microglobulin Kidney Disease Beta-2 Microglobulin Tumor Marker Bicarbonate (Total CO2) Bilirubin Blood Culture Blood Gases ...

  9. Coagulation Factors Test

    Science.gov (United States)

    ... Blood Testing Alpha-1 Antitrypsin Alpha-fetoprotein (AFP) Tumor Marker AMAS Aminoglycoside Antibiotics Ammonia Amniocentesis Amylase ANCA/MPO/ ... Beta-2 Microglobulin Kidney Disease Beta-2 Microglobulin Tumor Marker Bicarbonate (Total CO2) Bilirubin Blood Culture Blood Gases ...

  10. [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.

  11. X-linked mental deficiency.

    Science.gov (United States)

    des Portes, Vincent

    2013-01-01

    Ten percent of cases of intellectual deficiency in boys are caused by genes located on the X chromosome. X-linked mental retardation (XLMR) includes more than 200 syndromes and 80 genes identified to date. The fragile X syndrome is the most frequent syndrome, due to a dynamic mutation with a CGG triplet amplification. Mental retardation is virtually always present. Phonological and syntactic impairments are often combined with pragmatic language impairment and visuospatial reasoning difficulties. A minority fulfill the criteria for autism. In girls, the clinical expression of the complete mutation varies according to the X chromosome inactivation profile. Several XLMR occur as severe early onset encephalopathies: Lowe oculocerebrorenal syndrome, ATR-X syndrome (alpha thalassemia/mental retardation X-linked), Allan-Herdon-Dudley syndrome (MCT8 gene). Two genes, ARX (X-LAG; Partington syndrome) and MECP2 (Rett syndrome in females; mild MR with spastic diplegia/psychotic problems in males) are associated with various phenotypes, according to the mutation involved. Oligophrenine 1 (OPHN-1) gene mutations lead to vermal dysplasia. PQBP1 gene mutations (Renpenning syndrome) are responsible for moderate to severe mental deficiency, microcephaly, and small stature. Although some forms of XLMR are not very specific and the phenotype for each given gene is somewhat heterogeneous, a clinical diagnostic strategy is emerging. Copyright © 2013 Elsevier B.V. All rights reserved.

  12. Vitamin D deficiency and stroke

    Directory of Open Access Journals (Sweden)

    2012-12-01

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

  13. 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...

  14. The hobbit - an unexpected deficiency.

    Science.gov (United States)

    Hopkinson, Joseph A; Hopkinson, Nicholas S

    2013-12-16

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

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

    LENUS (Irish Health Repository)

    McGrath, T

    2018-01-01

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

  16. 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 ...

  17. Prenatal diagnostic procedure for leukocyte adhesion deficiency

    NARCIS (Netherlands)

    Weening, R. S.; Bredius, R. G.; Wolf, H.; van der Schoot, C. E.

    1991-01-01

    Leukocyte adhesion deficiency (LAD) is a rare autosomal recessive disorder which leads to recurrent severe infections due to impaired leukocyte functions. The disorder is caused by an absence or deficiency of leukocyte cell adhesion molecules (LeuCAMs) on the leukocyte membranes. The diagnosis is

  18. Genetics Home Reference: combined pituitary hormone deficiency

    Science.gov (United States)

    ... be associated with a deficiency of the hormone cortisol . Cortisol deficiency can impair the body's immune system, causing ... proteins called transcription factors, which help control the activity of many ... play a role in sexual development and the ability to have children (fertility); ...

  19. Nutrient deficiencies secondary to bariatric surgery.

    Science.gov (United States)

    Alvarez-Leite, Jacqueline I

    2004-09-01

    The number of adolescent and adult patients submitting to bariatric surgery is increasing rapidly around the world. This review describes the literature published in the last few years concerning nutritional deficiencies after bariatric surgery as well as their etiology, incidence, treatment and prevention. Although bariatric surgery was first introduced in the 1950s, safe and successful surgical management has progressed over the last two decades and longer post-surgical follow-up data are now available. Most of the patients undergoing malabsorptive procedures will develop some nutritional deficiency, justifying mineral and multivitamin supplementation to all postoperatively. Nutrient deficiency is proportional to the length of absorptive area and to the percentage of weight loss. Low levels of iron, vitamin B12, vitamin D and calcium are predominant after Roux-en-Y gastric bypass. Protein and fat-soluble vitamin deficiencies are mainly detected after biliopancreatic diversion. Thiamine deficiency is common in patients with frequent vomiting. As the incidence of these deficiencies progresses with time, the patients should be monitored frequently and regularly to prevent malnutrition. Nutritional deficiencies can be prevented if a multidisciplinary team regularly assists the patient. Malnutrition is generally reverted with nutrient supplementation, once it is promptly diagnosed. Especial attention should be given to adolescents, mainly girls at reproductive age who have a substantial risk of developing iron deficiency. Future studies are necessary to detect nutrient abnormalities after new procedures and to evaluate the safety of bariatric surgery in younger obese patients.

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

    African Journals Online (AJOL)

    admin

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

  1. INTRODUCTION Micronutrient deficiencies are becoming more ...

    African Journals Online (AJOL)

    the recommended strategy for the prevention of micronutrient deficiency, literature provides the basis for the adoption of supplementation programmes in certain circumstances, such as in cases of severe deficiencies. Evidence has shown that the rate of conversion of â-carotene in fruits and vegetables to retinol is less than ...

  2. Mechanism of hypercholesterolemia produced by biotin deficiency ...

    Indian Academy of Sciences (India)

    The effect of biotin deficiency on the metabolism of cholesterol was studied in rats fed cholesterol-free and cholesterol-containing diet. Biotin deficiency induced by feeding raw egg-white resulted in higher cholesterol in the serum and aorta, and higher high density lipoprotein cholesterol and low density lipoprotein + very ...

  3. Vitamin D Deficiency and Tuberculosis Progression

    OpenAIRE

    Talat, Najeeha; Perry, Sharon; Parsonnet, Julie; Dawood, Ghaffar; Hussain, Rabia

    2010-01-01

    To assess the association between vitamin D deficiency and tuberculosis disease progression, we studied vitamin D levels in a cohort of tuberculosis patients and their contacts (N = 129) in Pakistan. Most (79%) persons showed deficiency. Low vitamin D levels were associated with a 5-fold increased risk for progression to tuberculosis.

  4. Review Article: Practical Aspects of Testosterone Deficiency ...

    African Journals Online (AJOL)

    In this review we describe the clinical manifestations associated with testosterone deficiency in aging men, termed the testosterone deficiency syndrome (TDS). Since aging men suffer from multiple urological and andrological symptoms, TDS is an important medical condition to be suspected, recognized, clinically ...

  5. Ferrotherapy of iron deficiency anemia in children

    OpenAIRE

    Berezhniy V.V.; Korneva V.V.

    2016-01-01

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

  6. Genetics Home Reference: monoamine oxidase A deficiency

    Science.gov (United States)

    ... Sleep problems, such as trouble falling asleep or night terrors, can also occur in monoamine oxidase A deficiency . Some people with monoamine oxidase A deficiency have episodes of skin flushing, sweating, headaches, ... regulate mood, emotion, sleep, and appetite. Epinephrine and norepinephrine control the body's ...

  7. ADAPTATION TO PROTEIN DEFICIENCY: CORTISOL, THYROXINE ...

    African Journals Online (AJOL)

    Sci.6, I0I- 104 (1976). ADAPTATION TO PROTEIN DEFICIENCY: CORTISOL, THYROXINE,. INSULIN AND GLUCOSE IN YOUNG PIGS. J.M. van der Westhuysen*, P.C. Belonje**. A.P.D. de Satge*** & D.H. Holness***. Nutritional deficiencies place stress on the body. To maintain metabolic integrity. the body adapts by re-.

  8. 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.

  9. 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

  10. 2-Methylbutyryl-coenzyme A dehydrogenase deficiency

    DEFF Research Database (Denmark)

    Sass, Jörn Oliver; Ensenauer, Regina; Röschinger, Wulf

    2008-01-01

    -mass spectrometry due to elevated pentanoylcarnitine (C5 acylcarnitine) in blood, but little information is available on the clinical relevance of MBD deficiency. We biochemically and genetically characterize six individuals with MBD deficiency from four families of different ethnic backgrounds. None of the six...

  11. Growth hormone deficiency and hyperthermia during exercise

    DEFF Research Database (Denmark)

    Juul, A; Hjortskov, N; Jepsen, Leif

    1995-01-01

    levels [11 with multiple pituitary deficiency (MPD) and 5 with isolated GH deficiency] and in 10 healthy subjects as controls (CTs). Each subject exercised on a bicycle ergometer for 60 min at a workload corresponding to 45% of their individual maximal oxygen consumption (VO2max), in a room maintained...

  12. Thiamin deficiency in people with obesity.

    Science.gov (United States)

    Kerns, Jennifer C; Arundel, Cherinne; Chawla, Lakhmir S

    2015-03-01

    Although obesity has been viewed traditionally as a disease of excess nutrition, evidence suggests that it may also be a disease of malnutrition. Specifically, thiamin deficiency was found in 15.5-29% of obese patients seeking bariatric surgery. It can present with vague signs and symptoms and is often overlooked in patients without alcohol use disorders. This review explores the relatively new discovery of high rates of thiamin deficiency in certain populations of people with obesity, including the effects of thiamin deficiency and potential underlying mechanisms of deficiency in people with obesity. The 2 observational studies that examined the prevalence in preoperative bariatric surgery patients and gaps in our current knowledge (including the prevalence of thiamin deficiency in the general obese population and whether the current RDA for thiamin meets the metabolic needs of overweight or obese adults) are reviewed. Suggestions for future areas of research are included. © 2015 American Society for Nutrition.

  13. Nutrient deficiencies before and after sleeve gastrectomy.

    Science.gov (United States)

    van Rutte, P W J; Aarts, E O; Smulders, J F; Nienhuijs, S W

    2014-10-01

    Obesity is associated with nutritional deficiencies. Bariatric surgery could worsen these deficiencies. Fewer nutritional deficiencies would be seen after sleeve gastrectomy compared to the Roux-en-Y gastric bypass, but sleeve gastrectomy would also cause further deterioration of the deficiencies. The aim of this study was to determine the amount of pre-operative nutrient deficiencies in sleeve gastrectomy patients and assess the evolution of the nutritional status during the first post-operative year. Four hundred seven sleeve gastrectomy patients were assigned to a standardized follow-up program. Data of interest were weight loss, pre-operative nutrient status and evolution of nutrient deficiencies during the first post-operative year. Deficiencies were supplemented when found. Two hundred patients completed blood withdrawal pre-operatively and in the first post-operative year. pre-operatively, 5 % of the patients were anemic, 7 % had low serum ferritin and 24 % had low folic acid. Hypovitaminosis D was present in 81 %. Vitamin A had excessive levels in 72 %. One year post-operatively, mean excess weight loss was 70 %. Anemia was found in 6 %. Low-ferritin levels were found in 8 % of the patients. Folate deficiency decreased significantly and hypovitaminosis D was still found in 36 %. In this study, a considerable amount of patients suffered from a deficient micronutrient status pre-operatively. One year after surgery, micronutrient deficiencies persisted or were found de novo in a considerable amount of patients, despite significant weight loss and supplementation. Significant reductions were seen only for folate and vitamin D.

  14. 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

  15. Genetics Home Reference: leukocyte adhesion deficiency type 1

    Science.gov (United States)

    ... Home Health Conditions Leukocyte adhesion deficiency type 1 Leukocyte adhesion deficiency type 1 Printable PDF Open All ... Javascript to view the expand/collapse boxes. Description Leukocyte adhesion deficiency type 1 is a disorder that ...

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

    DEFF Research Database (Denmark)

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

    2009-01-01

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

  17. Genetics Home Reference: dopamine beta-hydroxylase deficiency

    Science.gov (United States)

    ... Twitter Home Health Conditions Dopamine beta-hydroxylase deficiency Dopamine beta-hydroxylase deficiency Printable PDF Open All Close ... Javascript to view the expand/collapse boxes. Description Dopamine beta (β)-hydroxylase deficiency is a condition that ...

  18. Diet Treatment Glucose Transporter Type 1 Deficiency (G1D)

    Science.gov (United States)

    2017-10-17

    GLUT1DS1; Epilepsy; Glut1 Deficiency Syndrome 1, Autosomal Recessive; Glucose Metabolism Disorders; Glucose Transport Defect; Glucose Transporter Type 1 Deficiency Syndrome; Glucose Transporter Protein Type 1 Deficiency Syndrome

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

    Science.gov (United States)

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

  20. Seventeen Alpha-hydroxylase Deficiency

    Directory of Open Access Journals (Sweden)

    Siew-Lee Wong

    2006-01-01

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

  1. Deficient approaches to human neuroimaging

    Science.gov (United States)

    Stelzer, Johannes; Lohmann, Gabriele; Mueller, Karsten; Buschmann, Tilo; Turner, Robert

    2014-01-01

    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 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. PMID:25071503

  2. 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.

  3. Prevalence of nutrient deficiencies in bariatric patients.

    Science.gov (United States)

    Toh, Seok Yee; Zarshenas, Nazy; Jorgensen, John

    2009-01-01

    The aims of this study were to determine the prevalence of nutrient deficiencies in patients who present for bariatric surgery, assess nutritional status after surgery, and compare these with preoperative levels. A retrospective study was conducted to identify preoperative and 1-year postoperative nutrition deficiencies in patients undergoing bariatric surgery. The screening included serum ferritin, vitamin D, vitamin B(12), homocysteine, folate, red blood cell folate, and hemoglobin. Results were available for 232 patients preoperatively and 149 patients postoperatively. Two-tailed chi(2) tests and paired-sample t tests were used. Preoperatively, vitamin D deficiency was noted at 57%. The prevalence of abnormalities 1 year after roux-en-Y gastric bypass was higher compared with preoperative levels (P surgery, anemia was detected in 17%, elevated homocysteine levels (women only) in 29%, low ferritin in 15%, low vitamin B(12) in 11%, and low RBC folate in 12%. Mean hemoglobin, ferritin, and RBC folate levels deteriorated significantly but remained well within normal ranges. The prevalence of vitamin D deficiencies decreased, but not significantly. In sleeve gastrectomy patients, mean ferritin levels decreased (P deficiency. Vitamin D deficiency is common among morbidly obese patients seeking bariatric surgery. Because the prevalence of micronutrient deficiencies persists or worsens postoperatively, routine nutrition screening, recommendation of appropriate supplements, and monitoring adherence are imperative in this population.

  4. [Deficiency of surfactant protein: Case report].

    Science.gov (United States)

    Milet, María Beatriz; Mena N, Patricia; Pérez, Héctor I; Espinoza, Tatiana

    Congenital surfactant deficiency is a condition infrequently diagnosed in newborns. A clinical case is presented of surfactant protein B deficiency. A review is performed on the study, treatment and differential diagnosis of surfactant protein deficiencies and infant chronic interstitial lung disease. The case is presented of a term newborn that developed respiratory distress, recurrent pulmonary opacification, and a transient response to the administration of surfactant. Immunohistochemical and genetic studies confirmed the diagnosis of surfactant protein B deficiency. Pulmonary congenital anomalies require a high index of suspicion. Surfactant protein B deficiency is clinically progressive and fatal in the majority of the cases, similar to that of ATP binding cassette subfamily A member 3 (ABCA3) deficiency. Protein C deficiency is insidious and may present with a radiological pulmonary interstitial pattern. Due to the similarity in the histological pattern, genetic studies help to achieve greater certainty in the prognosis and the possibility of providing adequate genetic counselling. Copyright © 2016 Sociedad Chilena de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

  5. 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.

  6. Copper Deficiency Myelopathy After Upper Gastrointestinal Surgery.

    Science.gov (United States)

    King, Dominic; Siau, Keith; Senthil, Latha; Kane, Katherine F; Cooper, Sheldon C

    2017-06-01

    A well-functioning alimentary canal is required for adequate nutrient absorption. Disruption to the upper gastrointestinal tract through surgery can lead to micronutrient malnourishment. Copper deficiency has been noted in up to 10% of those undergoing Roux-en-Y gastric bypass surgery, but sequalae are not frequently reported. The resultant deficiency states can have profound and long-term consequences if not realized early and managed appropriately. Here we present a case of copper deficiency myelopathy, a condition indistinguishable from subacute combined degeneration of the spinal cord, following upper gastrointestinal bypass surgery for gastric ulceration, further complicated by inadequate nutrition.

  7. Growth hormone deficiency and hyperthermia during exercise

    DEFF Research Database (Denmark)

    Juul, A; Hjortskov, N; Jepsen, Leif

    1995-01-01

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

  8. An uncommon presentation of hexosaminidase deficiency

    Directory of Open Access Journals (Sweden)

    Iype Mary

    2006-01-01

    Full Text Available Focal muscular atrophy (FMA can occur due to several causes. We report three cases of FMA associated with deficiency of hexosaminidase A. The serum level of hexosaminidase A was assayed in seven patients with FMA without any definite aetiology identified over a period of two years. Three cases of FMA showed deficiency of hexosaminidase A. All these patients had clinical features of isolated lower motor neurone involvement in one limb without any evidence of involvement of the rest of the neuraxis. Detailed laboratory tests were negative. Electromyography confirmed neurogenic involvement without any evidence of radiculopathy or neuropathy. Hexosaminidase deficiency as a possible association for FMA is highlighted.

  9. Patterns of chronic inflammation in extensively treated patients with arachnoiditis and chronic intractable pain.

    Science.gov (United States)

    Bilello, John A; Tennant, Forest S

    2017-01-01

    To use biomarkers to gain insight into and gauge the residual (post-treatment) level of inflammation in two groups of intensively treated patients with severe chronic pain. Three study groups were analyzed, and included: (i) patients (n = 90) with chronic intractable pain (CIP), (ii) patients (n = 26) with chronic pain and MRI-documented arachnoiditis (ARC) and (iii) normal subjects without a diagnosis of chronic pain (n = 86). We determined and compared the serum concentrations of Alpha-1 Antitrypsin (A1AT), Myeloperoxidase (MPO) and soluble Tumor Necrosis Factor receptor type 2 (sTNFR2) in each of the patient populations studied. Patients treated for ARC or CIP had higher serum levels of A1AT and MPO than normal untreated subjects without a diagnosis of chronic pain. ARC patients had an A1AT mean serum concentration of 167.9 ± 41.9 mg/dL as compared to 148.9 ± 35.2 mg/dL for normal subjects (p = 0.023). CIP patients had the highest mean serum A1AT level 183.6 ± 39.2 mg/dL with p values of pain, sites of neuroinflammation elaborate MPO and other inflammatory factors which may not be completely cleared from the system despite extensive and complex treatment regimens.

  10. Prenatal diagnosis in adenylosuccinate lyase deficiency

    NARCIS (Netherlands)

    Marie, S.; Flipsen, J. W.; Duran, M.; Poll-The, B. T.; Beemer, F. A.; Bosschaart, A. N.; Vincent, M. F.; van den Berghe, G.

    2000-01-01

    Adenylosuccinate lyase deficiency, an autosomal recessive inborn error of purine synthesis, provokes accumulation in body fluids of succinylaminoimidazolecarboxamide riboside and succinyladenosine, the dephosphorylated derivatives of the two substrates of the enzyme. Most patients display severe

  11. Genetics Home Reference: guanidinoacetate methyltransferase deficiency

    Science.gov (United States)

    ... movements (extrapyramidal dysfunction) such as tremors or facial tics. People with guanidinoacetate methyltransferase deficiency may have weak ... direct-to-consumer genetic testing? What is precision medicine? What is newborn screening? New Pages Depression GABA- ...

  12. LACTASE DEFICIENCY IN BABIES AND INFANTS

    Directory of Open Access Journals (Sweden)

    E.A. Kornienko

    2006-01-01

    Full Text Available Lactose, the constituent disaccharide of milk and other dairy products, is an important nutrient in early childhood. Lactase breaks down lactose in small intestine. In most people the activity of lactase reduces with age. In infancy lactase deficiency tends to be either transient, which is more often, or secondary to intestinal diseases. Abdominal cramps, anxiety and dyspepsia are the common symptoms of lactase deficiency. Tactics of treatment should take into account a cause and severity of the condition. A specialized milk formula «enfamil lactofree», distinguished for its' optimal formulation, high clinical effectiveness and good tolerance, could be recommended for use in children with primary, transient and secondary lactase deficiency who receive formula and mixed feeding.Key words: lactose, lactase deficiency, lactose-free formula.

  13. Patient reported outcome in posttraumatic pituitary deficiency

    DEFF Research Database (Denmark)

    Klose, Marianne; Stochholm, Kirstine; Janukonyté, Jurgita

    2015-01-01

    . RESULTS: Patients with TBI had significant detriments in QoL. Impairment (mainly physical scales) related to pituitary deficiency, although only partially confirmed after adjustment for demographic differences. Hypogonadotropic hypogonadism related to several QoL scores. Increasing impairments were...

  14. Genetics Home Reference: complement factor I deficiency

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    ... I deficiency: evaluation of three generations of a Brazilian family. Clin Exp Immunol. 2006 Feb;143(2): ... should consult with a qualified healthcare professional . About Selection Criteria for Links Data Files & API Site Map ...

  15. Growth hormone deficiency and hyperthermia during exercise

    DEFF Research Database (Denmark)

    Juul, A; Hjortskov, N; Jepsen, Leif

    1995-01-01

    levels [11 with multiple pituitary deficiency (MPD) and 5 with isolated GH deficiency] and in 10 healthy subjects as controls (CTs). Each subject exercised on a bicycle ergometer for 60 min at a workload corresponding to 45% of their individual maximal oxygen consumption (VO2max), in a room maintained......-deficiency may be at risk for developing hyperthermia. To pursue this, we performed a controlled study on sweating and body temperature regulation during exercise in the heat in 16 GH-treated GH-deficient patients with normalized insulin-like growth factor-I and insulin-like growth factor/binding protein-3 serum...... at 35 C. GH serum concentrations increased significantly after approximately 10 min of exercise in the CTs (P

  16. Genetics Home Reference: dihydrolipoamide dehydrogenase deficiency

    Science.gov (United States)

    ... Lacaille F, de Keyzer Y, Di Martino V, de Lonlay P. Dihydrolipoamide dehydrogenase deficiency: a still overlooked cause of recurrent acute liver failure and Reye-like syndrome. Mol Genet Metab. 2013 May;109(1):28- ...

  17. Genetics Home Reference: eosinophil peroxidase deficiency

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    ... navigation Home Page Search Home Health Conditions Genes Chromosomes & mtDNA Resources Help Me Understand Genetics Share: Email ... EPXD peroxidase and phospholipid deficiency in eosinophils Presentey anomaly Related Information How are genetic conditions and genes ...

  18. Genetics Home Reference: carnitine palmitoyltransferase I deficiency

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    ... SL, Raff ML. Novel mutations in CPT 1A define molecular heterogeneity of hepatic carnitine palmitoyltransferase I deficiency. ... for Links Data Files & API Site Map Subscribe Customer Support USA.gov Copyright Privacy Accessibility FOIA Viewers & ...

  19. Genetics Home Reference: beta-ureidopropionase deficiency

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    ... AB. Clinical, biochemical and molecular analysis of 13 Japanese patients with β-ureidopropionase deficiency demonstrates high prevalence ... of Medicine Lister Hill National Center for Biomedical Communications 8600 Rockville Pike, Bethesda, MD 20894, USA HONCode ...

  20. Genetics Home Reference: beta-ketothiolase deficiency

    Science.gov (United States)

    ... The mitochondrial acetoacetyl-CoA thiolase (T2) deficiency in Japanese patients: urinary organic acid and blood acylcarnitine profiles ... of Medicine Lister Hill National Center for Biomedical Communications 8600 Rockville Pike, Bethesda, MD 20894, USA HONCode ...