WorldWideScience

Sample records for molecular da hb

  1. Avaliação eletroforética, cromatográfica e molecular da Hb D Los Angeles no Brasil Electrophoretical, chromatographic and molecular valuations of Hb D Los Angeles in Brazil

    Directory of Open Access Journals (Sweden)

    Ana R. Chinelato-Fernandes

    2003-01-01

    Full Text Available A variante de hemoglobina (Hb D mais comum, Hb D Los Angeles ou D Punjab, é originada de uma transversão GAA->CAA no códon 121 da globina beta; essa mutação resulta na substituição do ácido glutâmico por glutamina na proteína. É a terceira variante de hemoglobina mais freqüente da população brasileira. Como as hemoglobinas D apresentam migração similar à hemoglobina S em pH alcalino, e com a hemoglobina A em pH ácido, são necessários vários testes para o correto diagnóstico. No presente estudo objetivou-se relacionar os diferentes procedimentos laboratoriais de rotina diagnóstica, além da análise molecular, para estabelecer o perfil de Hb D Los Angeles no Brasil. Foram analisados 47 indivíduos da população brasileira com provável Hb D Los Angeles, por vários procedimentos eletroforéticos em diferentes condições de pH, além da cromatografia líquida de alta pressão, e testes moleculares para confirmação da mutação. Foram encontrados quatro tipos de combinações de hemoglobinas: 42 indivíduos portadores de hemoglobina AD Los Angeles, dois indivíduos com doença de Hb S/D Los Angeles, dois indivíduos com Hb D Los Angeles e talassemia beta e um indivíduo com Hb D Los Angeles e Hb Lepore. Os indivíduos heterozigotos para D Los Angeles são assintomáticos, entretanto, em associação com outras variantes e talassemias podem apresentar graus variáveis de manifestações clínicas. Os resultados apresentados enfatizaram a necessidade da associação de várias metodologias para a identificação da Hb D Los Angeles, além de auxiliar na elucidação de combinações raras.The most common Hb D variant, the Hb D-Los Angeles, also know as Hb D-Punjab, originates through a GAA->CAA change at the 121 codon of the beta globin gene; this mutation results in the replacement of glutamic acid for glutamine in the protein. It is the third most common hemoglobin variant in the Brazilian population. This variant has

  2. Molecular analysis of Hb Q-H disease and Hb Q-Hb E in a Singaporean family.

    Science.gov (United States)

    Tan, J; Tay, J S; Wong, Y C; Kham, S K; Bte Abd Aziz, N; Teo, S H; Wong, H B

    1995-01-01

    Hb Q (alpha 74Asp-His) results from a mutation in the alpha-gene such that abnormal alpha Q-chains are synthesized. The alpha Q-chains combine with the normal Beta A-chains to form abnormal Hb alpha 2Q beta 2A (Hb Q). Hb Q-H disease is rare, and has been reported only in the Chinese. We report here a Chinese family, were the mother diagnosed with Hb Q-H disease and the father with Hb E heterozygosity and a child with Hb Q-E-thalassemia. Thalassemia screening of the mother's blood revealed a Hb level of 6.8g/dl with low MCV and MCH. Her blood film was indicative of thalassemia. Cellulose acetate electrophoresis showed Hb H and Hb Q with the absence of Hb A. Globin chain biosynthesis was carried out and alpha Q- and beta-chains were detected. Normal alpha- chains were absent. Digestion of the mother's DNA with Bam HI and Bgl II followed by hybridization with the 1.5 kb alpha-Pst probe showed a two alpha-gene deletion on one chromosome and the -alpha Q chain mutant with the -alpha 4.2 defect on the other chromosome. DNA amplification studies indicated the two-gene deletion to be of the -SEA/ defect. The patient was concluded to possess Hb Q-H disease (--SEA/-alpha 4.2Q). Cellulose acetate electrophoresis of the father's blood showed the presence of Hb A, F and E. Molecular analysis of the father's DNA confirmed an intact set of alpha-genes (alpha alpha/alpha alpha). Globin chain biosynthesis of fetal blood of their child showed gamma, beta A, beta E, alpha A and alpha Q-chains. Molecular analysis of the child's DNA showed one alpha-gene deletion, thus giving a genotype of alpha alpha/-alpha 4.2Q beta beta E.

  3. HB D Los Angeles in a Brazilian family Hb D Los Angeles em família brasileira

    Directory of Open Access Journals (Sweden)

    Guilherme G. Leoneli

    2001-09-01

    Full Text Available Inherited disorders of hemoglobin, the most common monogenic disease, are now well understood at the molecular level, knowledge, which has led to considerable improvements in their control and management. The Brazilian population is multiethnic, and the correct characterization of the Hb D is important, mainly because the method available for detection of abnormal hemoglobins, present a migration in the same zone at alkaline pH, for Hb S, D, and G for example. In this paper we studied a family with an abnormal hemoglobin like S in alkaline electrophoresis, by appropriated methods including HPLC and molecular analysis, characterized as hemoglobin D Los Angeles.As doenças hereditária da hemoglobina são as mais comuns doenças monogênicas e atualmente bem conhecidas do ponto de vista molecular, fato este que propiciou um avanço no seu controle e manuseio. A população brasileira caracteriza-se pela multiplicidade étnica e a caracterização da Hb D torna-se importante por este dado, associado ao fato de que os métodos de detecção das hemoglobinopatias comumente não identificam esta fração anormal que apresenta a peculiaridade de migração eletroforéticia em pH alcalino na mesma zona observada nas Hb S e G. Neste relato é apresentado um estudo familiar no qual é empregada metodologia adequada, o HLPC, que permite a identificação da Hb D.

  4. Avaliação eletroforética, cromatográfica e molecular da Hb D Los Angeles no Brasil

    OpenAIRE

    Chinelato-Fernandes Ana R.; Leoneli Guilherme G.; Calderan Patrícia O.; Oliveira Rute Blasi de; Silva Jr. Wilson Araújo da; Hidalgo Claudia Augusta; Bonini- Domingos Claudia Regina

    2003-01-01

    A variante de hemoglobina (Hb) D mais comum, Hb D Los Angeles ou D Punjab, é originada de uma transversão GAA->CAA no códon 121 da globina beta; essa mutação resulta na substituição do ácido glutâmico por glutamina na proteína. É a terceira variante de hemoglobina mais freqüente da população brasileira. Como as hemoglobinas D apresentam migração similar à hemoglobina S em pH alcalino, e com a hemoglobina A em pH ácido, são necessários vários testes para o correto diagnóstico. No presente estu...

  5. Electrochemical sensor based on magnetic molecularly imprinted nanoparticles modified magnetic electrode for determination of Hb.

    Science.gov (United States)

    Sun, Binghua; Ni, Xinjiong; Cao, Yuhua; Cao, Guangqun

    2017-05-15

    A fast and selective electrochemical sensor for determination of hemoglobin (Hb) was developed based on magnetic molecularly imprinted nanoparticles modified on the magnetic glassy carbon electrode. The nanoparticles Fe 3 O 4 @SiO 2 with a magnetic core and a molecularly imprinted shell had regular structures and good monodispersity. Hb could be determined directly by electrochemical oxidization with the modified electrode. A magnetic field increased electrochemical response to Hb by two times. Imprinting Hb on the surface of Fe 3 O 4 @SiO 2 shortened the response time within 7min. Under optimum conditions, the imprinting factor toward the non-imprinted sensor was 2.8, and the separation factor of Hb to horseradish peroxidase was 2.6. The oxidation peak current had a linear relationship with Hb concentration ranged from 0.005mg/ml to 0.1mg/ml with a detection limit (S/N =3) of 0.0010mg/ml. The sensors were successfully applied to analysis of Hb in whole blood samples with recoveries between 95.7% and 105%. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. A novel double heterozygous Hb Fontainebleau/HbD Punjab hemoglobinopathy.

    Science.gov (United States)

    Rodríguez-Capote, Karina; Estey, Mathew P; Barakauskas, Vilte; Bordeleau, Pierre; Christensen, Cathie-Lou; Zuberbuhler, Peter; Higgins, Trefor N

    2015-09-01

    To report the finding of a novel double heterozygous hemoglobinopathy, the coinheritance of Hb Fontainebleau (α-chain variant) with HbD-Punjab (β-chain variant) discovered upon investigation of unexplained microcytosis in an infant. Hemoglobinopathy investigation was performed by high performance liquid chromatography (HPLC) using the β-thalassemia Short Program on the Bio-Rad Variant II(TM) followed by gel electrophoresis at alkaline and acid pH (Sebia Hydrasys 2 Electrophoresis System) and molecular diagnostic testing. This study complied with our institutional board ethics requirements. HPLC and electrophoresis suggested a complex α- and β-chain hemoglobinopathy with presumptive identification of the beta Hb variant as Hb D-Punjab. DNA sequencing analysis revealed the presence of a double heterozygous status for Hb Fontainebleau/Hb D-Punjab. In this paper we report the coinheritance of Hb Fontainebleau with Hb D-Punjab. Copyright © 2015 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  7. Análise quantitativa e molecular de hemoglobina fetal em indivíduos da população brasileira

    Directory of Open Access Journals (Sweden)

    Zamaro Paula J. A.

    2003-01-01

    Full Text Available A hemoglobina fetal - Hb F, formada por duas cadeias gama e duas cadeias alfa, é característica do período fetal do desenvolvimento, tendo sua síntese diminuída no período pós-natal. Em algumas alterações hereditárias, a Hb F permanece aumentada, como nas delta-beta talassemia, beta talassemia e persistência hereditária de Hb F (PHHF. A síntese da globina gama também pode ser estimulada por fatores externos como leucemias, transplantes de medula óssea, induções químicas, dentre outros. Através da observação de Hb F aumentada em doadores de sangue por procedimentos eletroforéticos objetivou-se avaliar a quantidade de Hb F em amostras de sangue de candidatos à doação, visando estabelecer seus limites de normalidade na população de São José do Rio Preto e região, por meio de desnaturação alcalina e cromatografia líquida de alta pressão (HPLC, comparar as metodologias aplicadas e, nos indivíduos com Hb F aumentada, realizar estudos moleculares para identificar as mutações que alteram a expressão dos genes gama. Foram analisadas 208 amostras de sangue, sendo 119 de candidatos à doação e 89 de indivíduos sem sintomas de anemia ou achados hematológicos e com Hb F aumentada como grupo comparativo. Das 119 amostras de candidatos à doação, 110 foram utilizadas para traçar o perfil de normalidade de Hb F, comparando-se as metodologias de desnaturação alcalina e HPLC, onde se obteve a média de 1,48% e de 0,6%, respectivamente. A análise estatística por regressão linear mostrou diferença significativa na comparação entre as duas metodologias aplicadas, sendo a HPLC mais precisa para a quantificação de Hb F. Foram observados nos testes de rastreamento de hemoglobinas anormais nestas 110 amostras de sangue: 16,4% de alfa talassemia, 0,9% com Hb F aumentada, 0,9% com beta talassemia e 0,9% com hemoglobina variante de cadeia delta. Os outros nove doadores de sangue apresentaram Hb F acima de 10% em

  8. Erroneous HbA1c results in a patient with elevated HbC and HbF.

    Science.gov (United States)

    Adekanmbi, Joy; Higgins, Trefor; Rodriguez-Capote, Karina; Thomas, Dylan; Winterstein, Jeffrey; Dixon, Tara; Gifford, Jessica L; Krause, Richard; Venner, Allison A; Clarke, Gwen; Estey, Mathew P

    2016-11-01

    HbA1c is used in the diagnosis and monitoring of diabetes mellitus (DM). Interference from hemoglobin variants is a well-described phenomenon, particularly with HPLC-based methods. While immunoassays may generate more reliable HbA1c results in the presence of some variants, these methods are susceptible to negative interference from high concentrations of HbF. We report a case where an accurate HbA1c result could not be obtained by any available method due to the presence of a compound hemoglobinopathy. HbA1c was measured by HPLC, immunoassay, and capillary electrophoresis. Hemoglobinopathy investigation consisted of a CBC, hemoglobin fractionation by HPLC and electrophoresis, and molecular analysis. HbA1c analysis by HPLC and capillary electrophoresis gave no result. Analysis by immunoassay yielded HbA1c results of 5.9% (Siemens DCA 2000+) and 5.1% (Roche Integra), which were inconsistent with other markers of glycemic control. Hemoglobinopathy investigation showed HbC with the hereditary persistence of fetal hemoglobin-2 Ghana deletion. Reliable HbA1c results may be unobtainable in the presence of some hemoglobinopathies. HPLC and capillary electrophoresis alerted the laboratory to the presence of an unusual hemoglobinopathy. Immunoassays generated falsely low results without warning, which could lead to missed diagnoses and under treatment of patients with DM. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Diagnosis of Compound Heterozygous Hb Tak/β-Thalassemia and HbD-Punjab/β-Thalassemia by HbA2 Levels on Capillary Electrophoresis.

    Science.gov (United States)

    Panyasai, Sitthichai; Sakkhachornphop, Supachai; Pornprasert, Sakorn

    2018-01-01

    A misdiagnosis of β-thalassemia carrier in samples with Hb Tak and HbD-Punjab, the β-variants, can be a cause of inappropriate genetic counseling thus having a new case of β-thalassemia major. A capillary electrophoresis (CE) is very efficient in separating and quantifying HbA 2 . In this study, HbA 2 levels of samples which were doubted for compound heterozygous Hb Tak/β-thalassemia or heterozygous HbD-Punjab/β-thalassemia were measured and compared between CE and high performance liquid chromatography (HPLC). The molecular confirmation for Hb Tak, HbD-Punjab and β-thalassemia codons 17 (A > T), 41/42 (-TCTT), 71/72 (+A) and IVSI-nt1 (G > T) mutations and 3.4 kb deletion were also performed. Based on DNA analysis, 3 cases were diagnosed as compound heterozygous Hb Tak/β-thalassemia and one for HbD-Punjab/β-thalassemia. The elevated HbA 2 levels were found in all 4 samples with rages of 4.6-7.3% on CE while those were not found on HPLC. Thus, the elevated HbA 2 measured by CE can be used as a screening parameter for differentiating the homozygote of Hb Tak and HbD-Punjab from the compound heterozygote of these hemoglobinopathies and β-thalassemia.

  10. Biochemical and Molecular Analysis of the Hb Lepore Boston Washington in a Syrian Homozygous Child

    Directory of Open Access Journals (Sweden)

    Monica Pirastru

    2017-01-01

    Full Text Available Hemoglobin (Hb Lepore is composed of two normal α chains and two δβ fusion globins that arise from unequal crossover events between the δ- and β-globin genes. The Hb Lepore is widespread all over the world and in many ethnic groups. It includes some of the few clinically significant Hb variants that are associated with a β-thalassemia phenotype. Here, we describe the first occurrence of Hb Lepore Boston Washington in a Syrian individual. The patient, a 10-year-old child, shows severe anemia with a Hb level of 6.85 g/dL and typical thalassemic red cell indices. The diagnostic procedure implies hematological, biochemical, and molecular analysis, including multiplex ligation-dependent probe amplification (MLPA assay, GAP-PCR, and DNA sequencing. This latter allowed us to define the correct structure of the hybrid δβ-globin gene. The knowledge of the spectrum of mutations associated with different geographical areas is the prerequisite to set up large-scale screening programs and be able to offer genetic counseling to couples at risk.

  11. Novel interactions of two α-Hb variants with SEA deletion α0-thalassemia: hematological and molecular analyses.

    Science.gov (United States)

    Srivorakun, Hataichanok; Singha, Kritsada; Fucharoen, Goonnapa; Fucharoen, Supan

    2018-04-01

    To report the hematological and molecular features as well as diagnostic aspects of the hitherto un-described interactions of two rare α-globin chain variants with α 0 -thalassemia commonly found among Southeast Asian populations. The study was done on two adult Thai patients (P1 and P2) who had hypochromic microcytic anemia. Hb analysis was carried out using high performance liquid chromatography (HPLC) and capillary electrophoresis (CE). Mutations were identified by PCR and related techniques. Hb analysis of P1 using HPLC showed a normal Hb pattern, but CE demonstrated an abnormal peak at zone 7. DNA sequencing identified a CCG-CTG mutation at codon 95 of the α2 globin gene corresponding to the Hb G-Georgia [α95(G2)Pro → Leu(α2)] previously undescribed in the Thai population. In contrast, Hb analysis of P2 demonstrated an abnormal peak not fully separated from Hb A on HPLC, but not on CE. DNA analysis identified the rarely described Hb Nakhon Ratchasima [α63(E12)Ala → Val(α2)] mutation. Routine DNA analysis detected the SEA deletion α 0 -thalassemia in trans to the Hb variants in both cases. Hematological parameters were compared with those of patients with compound heterozygote for other α-globin variants and α 0 -thalassemia previously documented. Identification of the patients confirmed that interaction of these rare Hb variants with α 0 -thalassemia does not lead to the Hb H disease. Differentiation of these two Hb variants from other clinically relevant hemoglobinopathies in a routine setting is, however, necessary. This can be accomplished using a combined Hb-HPLC and CE analysis followed by PCR-RFLP assays.

  12. Cloning and molecular characterization of a copper chaperone gene ...

    African Journals Online (AJOL)

    The cDNA encoding a copper chaperone, designated as HbCCH1, was isolated from Hevea brasiliensis. HbCC1 was 589 bp long containing a 261 bp open reading frame encoding a putative protein of 86 amino acids, flanked by a 103 bp 5'UTR and a 225 bp 3'UTR. The predicted molecular mass of HbCCH1 was 9.2 kDa, ...

  13. The significance of disulfide bonding in biological activity of HB-EGF, a mutagenesis approach

    International Nuclear Information System (INIS)

    Hoskins, J.T.; Zhou, Z.; Harding, P.A.

    2008-01-01

    A site-directed mutagenesis approach was taken to disrupt each of 3 disulfide bonds within human HB-EGF by substituting serine for both cysteine residues that contribute to disulfide bonding. Each HB-EGF disulfide analogue (HB-EGF-Cys/Ser 108/121 , HB-EGF-Cys/Ser 116/132 , and HB-EGF-Cys/Ser 134/143 ) was cloned under the regulation of the mouse metallothionein (MT) promoter and stably expressed in mouse fibroblasts. HB-EGF immunoreactive proteins with M r of 6.5, 21 and 24 kDa were observed from lysates of HB-EGF and each HB-EGF disulfide analogue. HB-EGF immunohistochemical analyses of each HB-EGF stable cell line demonstrated ubiquitous protein expression except HB-EGF-Cys/Ser 108/121 and HB-EGF-Cys/Ser 116/132 stable cell lines which exhibited accumulated expression immediately outside the nucleus. rHB-EGF, HB-EGF, and HB-EGF 134/143 proteins competed with 125 I-EGF in an A431 competitive binding assay, whereas HB-EGF-Cys/Ser 108/121 and HB-EGF-Cys/Ser 116/132 failed to compete. Each HB-EGF disulfide analogue lacked the ability to stimulate tyrosine phosphorylation of the 170 kDa EGFR. These results suggest that HB-EGF-Cys/Ser 134/143 antagonizes EGFRs

  14. Aspectos moleculares da anemia falciforme

    Directory of Open Access Journals (Sweden)

    Galiza Neto Gentil Claudino de

    2003-01-01

    Full Text Available No presente artigo abordaram-se vários aspectos relacionados à natureza molecular da anemia falciforme, desordem hematológica de caráter hereditário que acomete expressivo número de indivíduos em várias regiões do mundo. As pesquisas realizadas em torno desta patologia da hemácia, ao longo de quase um século, a partir de 1910, cooperaram para a criação de um novo e importante segmento da ciência, denominado biologia molecular. A descoberta dos polimorfismos da mutação (GAT->GTG no gene que codifica a cadeia beta da hemoglobina, originando diferentes haplótipos da doença, permitiu um melhor e mais amplo conhecimento em torno da heterogeneidade clínica nos pacientes falcêmicos. Analisando a hemoglobina na sua estrutura normal e mutante, sua produção e evolução, pode-se ter um entendimento mais completo da fisiopatologia desta doença e da sua complexidade clínica.

  15. Hematological and Molecular Characterization of Hb J-Buda [α61(E10)Lys → Asn, AAG > AAT].

    Science.gov (United States)

    Panyasai, Sitthichai; Permsripong, Nopphadol; Jaiping, Kanokwan; Khantarag, Pisuttinee; Pornprasert, Sakorn

    2016-06-01

    Hemoglobin (Hb) J-Buda [α61(E10)Lys → Asn, AAG > AAT] is a very rare α-chain variant found in South-East Asia. We analyzed hematological parameters and provided a rapid molecular analysis method for detection of this hemoglobinopathy in two Thai women who had severe microcytic anemia with Hb and MCV AAG → AAT mutation at codon 61 for Hb J-Buda on one allele of the α1-globin gene. The developed Allele-specific PCR (ASPCR) showed the 455 bp amplified fragment from Hb J-Buda allele. Thus, understanding of hematological characterizations and the developed ASPCR for diagnosis of Hb J-Buda are essential for genetic counseling of this hemoglobinopathy.

  16. Co-inheritance of α0 -thalassemia elevates Hb A2 level in homozygous Hb E: Diagnostic implications.

    Science.gov (United States)

    Singha, K; Srivorakun, H; Fucharoen, G; Fucharoen, S

    2017-10-01

    Differentiation of homozygous hemoglobin (Hb) E with and without α 0 -thalassemia is subtle on routine hematological ground. We examined in a large cohort of homozygous Hb E if the level of Hb A 2 is helpful. A total of 592 subjects with homozygous Hb E were recruited from ongoing thalassemia screening program. Additionally, five couples at risk of having fetuses with Hb Bart's hydrops fetalis who were homozygous Hb E were also investigated. Hb analysis was performed using capillary electrophoresis system. Globin genotypes were defined by DNA analysis. Subjects were classified into four groups including pure homozygous Hb E (n=532), homozygous Hb E/α 0 -thalassemia (n=48), Hb Constant Spring EE Bart's disease (n=8), and Hb EE Bart's disease (n=4). The levels of Hb A 2 were found, respectively, to be 4.97±0.69, 6.64±1.02, 4.86±0.87, and 7.60±1.04%. Among five couples at risk, α 0 -thalassemia was identified in three subjects with Hb A 2 >6.0%. Increased Hb A 2 level is a useful marker for differentiation of homozygous Hb E with and without α 0 -thalassemia. This should lead to a significant reduction in number of referral cases of homozygous Hb E for molecular testing of α 0 -thalassemia in routine practice. © 2017 John Wiley & Sons Ltd.

  17. Clinical and molecular genetic features of Hb H and AE Bart's diseases in central Thai children.

    Science.gov (United States)

    Traivaree, Chanchai; Boonyawat, Boonchai; Monsereenusorn, Chalinee; Rujkijyanont, Piya; Photia, Apichat

    2018-01-01

    α-Thalassemia, one of the major thalassemia types in Thailand, is caused by either deletion or non-deletional mutation of one or both α-globin genes. Inactivation of three α-globin genes causes hemoglobin H (Hb H) disease, and the combination of Hb H disease with heterozygous hemoglobin E (Hb E) results in AE Bart's disease. This study aimed to characterize the clinical and hematological manifestations of 76 pediatric patients with Hb H and AE Bart's diseases treated at Phramongkutklao Hospital, a tertiary care center for thalassemia patients in central Thailand. Seventy-six unrelated pediatric patients, 58 patients with Hb H disease and 18 patients with AE Bart's disease, were enrolled in this study. Their clinical presentations, transfusion requirement, laboratory findings, and mutation analysis were retrospectively reviewed and analyzed. A total of 76 pediatric patients with Hb H and AE Bart's diseases who mainly lived in central Thailand were included in this study. The clinical severities of patients with non-deletional mutations were more severe than those with deletional mutations. Eighty-six percent of patients with non-deletional AE Bart's disease required more blood transfusion compared to 12.5% of patients with deletional AE Bart's disease. Non-deletional AE Bart's disease also had a history of urgent blood transfusion with the average of 6±0.9 times compared to 1±0.3 times in patients with deletional Hb H disease. The difference was statistically significant. This study revealed the differences in clinical spectrum between patients with Hb H disease and those with AE Bart's disease in central Thailand. The differentiation of α-thalassemia is essential for appropriate management of patients. The molecular diagnosis is useful for diagnostic confirmation and genotype-phenotype correlation.

  18. Molecular Characteristics of Hb New York [β113(G15)Val→Glu, HBB: c.341T>A] in Thailand.

    Science.gov (United States)

    Chaibunruang, Attawut; Singha, Kritsada; Srivorakun, Hataichanok; Fucharoen, Goonnapa; Fucharoen, Supan

    2018-01-01

    Hb New York or Hb Kaohsiung [β113(G15)Val→Glu (GTG>GAG), HBB: c.341T>A] has been considered a rare β hemoglobin (Hb) variant found originally in an Iranian woman and later in diverse populations but its genetic origin has not been elucidated. Here we report molecular and hematological descriptions of this variant found in the Thai population. Among 5643 subjects referred for hemoglobinopathy investigation during January 2015 to September 2017, 183 (3.2%) were found to carry several Hb variants, including β chain variants (n = 135, 2.4%), α chain variants (n = 33, 0.6%), Hb Lepore-Hollandia (NG_000007.3: g.63290_70702del) and Hb Lepore-Boston-Washington (NG_000007.3: g.63632_71046del) (δβ hybrid Hb) (n = 12, 0.2%) and δ chain variants (n = 3, 0.05%). Of patients with β chain variants, six with normal high performance liquid chromatography (HPLC) patterns, had an abnormal Hb in zone 11 of capillary electrophoresis (CE), the amounts of which ranged from 29.6-45.4% with normal levels of Hb A 2 and Hb F. DNA analysis identified a heterozygous Hb New York mutation in all cases. Further screening of α-thalassemia (α-thal) identified coinheritance of α + - and α 0 -thal in two of them who had reduced levels of Hb New York. Haplotype analysis suggested that the Thai Hb New York was likely associated with a single β-globin haplotype [+ - - - - + +], indicating that it was of the same origin. Hematological findings and simple DNA assay based on allele-specific polymerase chain reaction (PCR) for rapid detection of Hb New York are presented.

  19. Coinheritance of High Oxygen Affinity Hb Helsinki [HBB: c.248A>T; β82(EF6)Lys→Met] with Hb H Disease.

    Science.gov (United States)

    Lee, Shir-Ying; Goh, Jia-Hui; Tan, Karen M L; Liu, Te-Chih

    2017-05-01

    Hb Helsinki [HBB: c.248A>T; β82(EF6)Lys→Met] is a high oxygen affinity hemoglobin (Hb) causing polycythemia, whereas Hb H (β4) disease causes mild to severe chronic hemolytic anemia. The clinical characteristics, gel electrophoresis, capillary electrophoresis (CE) and molecular genotyping of a case of Hb Helsinki coinherited with Hb H disease in an ethnic Malay is described, illustrating the interaction between the β-globin variant and coinheritance of three α gene deletions. The proband was asymptomatic, exhibited microcytosis and a normal with Hb value.

  20. Diagnosis of a rare double heterozygous Hb D Punjab/Hb Q India hemoglobinopathy using Sebia capillary zone electrophoresis

    Directory of Open Access Journals (Sweden)

    Sushama Parab

    2014-01-01

    Full Text Available In India, hemoglobinopathies constitute a major genetic disorder and hemoglobin variants such as Hb S, Hb D Punjab, and Hb E are the most common ones. Other variants include Hb Q India, Hb Lepore, Hb J Meerut, Hb D Iran, etc. These variants show heterozygous state along with beta thalassemia. However, compound heterozygosities among these variants are very rare. Ethylenediaminetetraacetic acid whole blood sample received for routine thalassemia screening was subjected to alkaline electrophoresis using automated capillary zone electrophoresis. Suspecting the presence of rare variants, further analysis was carried out using Bio-Rad D10 and Tosoh G8 high-performance liquid chromatography (HPLC systems. Capillary zone electrophoretograms showed the presence of peaks in zone Hb A, Hb D, a fused peak in Hb A2, and a small peak in Z1 zone. Bio-Rad and Tosoh chromatograms also indicated the presence of four peaks which are identified as Hb A, Hb D Punjab, Hb Q India, and hybrid of Hb D Punjab/Hb Q India. A peak in Hb D zone of capillary was due to co-migration of Hb D Punjab and Hb Q India variants. Small peak in Z1 zone indicated the presence of alpha chain variant Hb Q India. The findings were further confirmed by HPLC results and molecular genetic studies. The present study reports for the 1 st time a rare hemoglobinopathy of double heterozygosity for Hb D Punjab, Hb Q India on Capillarys 2 Flex Piercing analyzer and is forth reported case for this rare hemoglobinopathy.

  1. Iron deficiency anemia interfering the diagnosis of compound heterozygosity for Hb constant spring and Hb Paksé: The first case report.

    Science.gov (United States)

    Chiasakul, Thita; Uaprasert, Noppacharn

    2018-01-01

    Diagnosis of thalassemia or hemoglobinopathy concomitant with iron deficiency anemia (IDA) is challenging. We report a case of 43-year-old female whose diagnosis of compound heterozygosity for hemoglobin Constant Spring (HbCS) and Hb Paksé became apparent after the treatment of IDA. Prior to treatment, Hb analysis using isoelectric focusing (IEF) showed HbA 95.6%, HbA 2 2.7%, and HbCS 1.7% compatible with heterozygous HbCS. After 4 months of oral iron therapy resulting in an improved Hb level, her HbCS level was substantially increased to 8.7% on IEF suggesting homozygous HbCS. Subsequent DNA analysis using multiplex amplification refractory mutation system analysis revealed compound heterozygosity for HbCS and Hb Paksé. This case demonstrated that IDA can significantly reduce HbCS/Hb Paksé levels and probably mask the diagnosis of homozygous HbCS, homozygous Hb Paksé or the compound heterozygosity for both hemoglobinopathies by hemoblogin analysis. The test should be repeated after resolution of IDA, or molecular testing should be performed to confirm the diagnosis. © 2017 Wiley Periodicals, Inc.

  2. Probing the diphosphoglycerate binding pocket of HbA and HbPresbyterian (beta 108Asn --> Lys).

    Science.gov (United States)

    Gottfried, D S; Manjula, B N; Malavalli, A; Acharya, A S; Friedman, J M

    1999-08-31

    HbPresbyterian (beta 108Asn --> Lys, HbP) contains an additional positive charge (per alpha beta dimer) in the middle of the central cavity and exhibits a lower oxygen affinity than wild-type HbA in the presence of chloride. However, very little is known about the molecular origins of its altered functional properties. In this study, we have focused on the beta beta cleft of the Hb tetramer. Recently, we developed an approach for quantifying the ligand binding affinity to the beta-end of the Hb central cavity using fluorescent analogues of the natural allosteric effector 2, 3-diphosphoglycerate (DPG) [Gottfried, D. S., et al. (1997) J. Biol. Chem. 272, 1571-1578]. Time-correlated single-photon counting fluorescence lifetime studies were used to assess the binding of pyrenetetrasulfonate to both HbA and HbP in the deoxy and CO ligation states under acidic and neutral pH conditions. Both the native and mutant proteins bind the probe at a weak binding site and a strong binding site; in all cases, the binding to HbP was stronger than to HbA. The most striking finding was that for HbA the binding affinity varies as follows: deoxy (pH 6.35) > deoxy (pH 7.20) > CO (pH 6.35); however, the binding to HbP is independent of ligation or pH. The mutant oxy protein also hydrolyzes p-nitrophenyl acetate, through a reversible acyl-imidazole pathway linked to the His residues of the beta beta cleft, at a considerably higher rate than does HbA. This implies a perturbation of the microenvironment of these residues at the DPG binding pocket. Structural consequences due to the presence of the new positive charge in the middle of the central cavity have been transmitted to the beta beta cleft of the protein, even in its liganded conformation. This is consistent with a newly described quaternary state (B) for liganded HbPresbyterian and an associated change in the allosteric control mechanism.

  3. Aspectos moleculares da anemia falciforme Molecular aspects for sickle cell anemia

    Directory of Open Access Journals (Sweden)

    Gentil Claudino de Galiza Neto

    2003-01-01

    Full Text Available No presente artigo abordaram-se vários aspectos relacionados à natureza molecular da anemia falciforme, desordem hematológica de caráter hereditário que acomete expressivo número de indivíduos em várias regiões do mundo. As pesquisas realizadas em torno desta patologia da hemácia, ao longo de quase um século, a partir de 1910, cooperaram para a criação de um novo e importante segmento da ciência, denominado biologia molecular. A descoberta dos polimorfismos da mutação (GAT->GTG no gene que codifica a cadeia beta da hemoglobina, originando diferentes haplótipos da doença, permitiu um melhor e mais amplo conhecimento em torno da heterogeneidade clínica nos pacientes falcêmicos. Analisando a hemoglobina na sua estrutura normal e mutante, sua produção e evolução, pode-se ter um entendimento mais completo da fisiopatologia desta doença e da sua complexidade clínica.The present article dealt with various aspects related to molecular nature of sickle cell disease (SCD, a heritable hematology disorder that attacks a great number of people in different regions of the world. Researches done on red cell patology, in approximately half a century, starting since 1910, cooperated to gave origin a new branch of science called molecular biology. The discovery of mutation polymorphism (GAT -> GTC in the gene that codifies beta globin chain, give origin to different illness haplotypes, permitted a better and great knowledge about the clinic heterogeneity of the patients. Analysing hemoglobin in its normal and mutation structure as well as in its productions and evolution, one can have a complete understanding of the illness phisiopathology and its clinical complexity.

  4. The significance of disulfide bonding in biological activity of HB-EGF, a mutagenesis approach

    OpenAIRE

    Hoskins, J.T.; Zhou, Z.; Harding, P.A.

    2008-01-01

    A site-directed mutagenesis approach was taken to disrupt each of 3 disulfide bonds within human HB-EGF by substituting serine for both cysteine residues that contribute to disulfide bonding. Each HB-EGF disulfide analogue (HB-EGF-Cys/Ser108/121, HB-EGF-Cys/Ser116/132, and HB-EGF-Cys/Ser134/143) was cloned under the regulation of the mouse metallothionein (MT) promoter and stably expressed in mouse fibroblasts. HB-EGF immunoreactive proteins with Mr of 6.5, 21 and 24kDa were observed from lys...

  5. As bases moleculares da hemofilia A

    Directory of Open Access Journals (Sweden)

    Simone Ferreira Pio

    2009-01-01

    Full Text Available As hemofilias são doenças hemorrágicas resultantes da deficiência de fator VIII (hemofilia A ou de fator IX (hemofilia B da coagulação, decorrentes de mutações nos genes que codificam os fatores VIII ou IX, respectivamente. A hemofilia A é mais frequente que a hemofilia B e acomete aproximadamente 1:10.000 nascimentos masculinos. A gravidade e frequência dos episódios hemorrágicos está relacionado ao nível residual de atividade de fator VIII presente no plasma e este relaciona-se ao tipo de mutação associada à doença. A clonagem do gene do fator VIII tornou possível o conhecimento das bases moleculares da hemofilia A, sendo hoje conhecidas mais de 1.000 mutações associadas à doença. O conhecimento das bases moleculares da hemofilia A permite uma melhor compreensão da relação genótipo-fenótipo da doença, tomada de condutas clínicas diferenciadas em casos de mutações associadas a um maior risco de desenvolvimento de inibidor, determinação da condição de portadora de hemofilia em mulheres relacionadas aos pacientes, implementação de programa de aconselhamento genético/orientação familiar e melhor compreensão das relações estruturais-funcionais do gene-proteína. Este artigo propõe revisar as bases moleculares da hemofilia A, os métodos laboratoriais utilizados para a caracterização das mutações e as implicações clínicas envolvidas no diagnóstico molecular da hemofilia A.Hemophilias are bleeding disorders due to deficiency of the blood coagulation factor VIII (hemophilia A or factor IX (hemophilia B, resulting from mutation on the gene coding for factor VIII or factor IX. Hemophilia A is more frequent than hemophilia B and affects 1:10,000 male newborns. The severity and frequency of hemorrhagic episodes is related to residual activity of factor VIII present in the plasma and relates to the type of mutation associated with the disorder. Cloning of the factor VIII gene has enabled researchers to

  6. HB Puerta del Sol [HBA1:c.148A>C], HB Valdecilla [HBA2:c.3G>T], HB Gran Vía [HBA2:c.98T>G], HB Macarena [HBA2:c.358C>T] and HB El Retiro [HBA2:c.364_366dupGTG]: description of five new hemoglobinopathies.

    Science.gov (United States)

    de la Fuente-Gonzalo, Félix; Nieto, Jorge M; Velasco, Diego; Cela, Elena; Pérez, Germán; Fernández-Teijeiro, Ana; Escudero, Antonio; Villegas, Ana; González-Fernández, Fernando A; Ropero, Paloma

    2016-04-01

    Structural hemoglobinopathies do not usually have a clinical impact, but they can interfere with the analytical determination of some parameters, such as the glycated hemoglobin in diabetic patients. Thalassemias represent a serious health problem in areas where their incidence is high. The defects in the post-translational modifications produce hyper-unstable hemoglobin that is not detected by most of electrophoretic or chromatographic methods that are available so far. We studied seven patients who belong to six unrelated families. The first two families were studied because they had peak abnormal hemoglobin (Hb) during routine analytical assays. The other four families were studied because they had microcytosis and hypochromia with normal HbA2 and HbF without iron deficiency. HbA2 and F quantification and abnormal Hb separation were performed by chromatographic and electrophoretic methods. The molecular characterization was performed using specific sequencing. The Hb Puerta del Sol presents electrophoretic mobility and elution in HPLC that is different from HbA and similar to HbS. The electrophoretic and chromatographic profiles of the four other variants are normal and do not show any anomalies, and their identification was only possible with sequencing. Some variants, such as Hb Valdecilla, Hb Gran Vía, Hb Macarena and Hb El Retiro, have significant clinical impact when they are associated with other forms of α-thalassemia, which could lead to more serious forms of this group of pathologies as for HbH disease. Therefore, it is important to maintain an adequate program for screening these diseases in countries where the prevalence is high to prevent the occurrence of severe forms.

  7. Cloning and characterization of HbMT2a, a metallothionein gene from Hevea brasiliensis Muell. Arg differently responds to abiotic stress and heavy metals

    Energy Technology Data Exchange (ETDEWEB)

    Li, Yan; Chen, Yue Yi; Yang, Shu Guang; Tian, Wei Min, E-mail: wmtian9110@126.com

    2015-05-22

    Metallothioneins (MTs) are of low molecular mass, cysteine-rich proteins. They play an important role in the detoxification of heavy metals and homeostasis of intracellular metal ions, and protecting against intracellular oxidative damages. In this study a full-length cDNA of type 2 plant metallothioneins, HbMT2a, was isolated from 25 mM Polyethyleneglycol (PEG) stressed leaves of Hevea brasiliensis by RACE. The HbMT2a was 372 bp in length and had a 237 bp open reading frame (ORF) encoding for a protein of 78 amino acid residues with molecular mass of 7.772 kDa. The expression of HbMT2a in the detached leaves of rubber tree clone RY7-33-97 was up-regulated by Me-JA, ABA, PEG, H{sub 2}O{sub 2}, Cu{sup 2+} and Zn{sup 2+}, but down-regulated by water. The role of HbMT2a protein in protecting against metal toxicity was demonstrated in vitro. PET-28a-HbMT2-beared Escherichia coli. Differential expression of HbMT2a upon treatment with 10 °C was observed in the detached leaves of rubber tree clone 93-114 which is cold-resistant and Reken501 which is cold-sensitive. The expression patterns of HbMT2a in the two rubber tree clones may be ascribed to a change in the level of endogenous H{sub 2}O{sub 2}. - Highlights: • Cloning an HbMT2a gene from rubber tree. • Analyzing expression patterns of HbMT2a upon abiotic stress and heavy metal stress. • Finding different expression patterns of HbMT2a among two Hevea germplasm. • The expressed protein of HbMT2a enhances copper and zinc tolerance in Escherichia coli.

  8. Functional behavior of tortoise hemoglobin Geochelone denticulata Comportamento funcional da hemoglobina da tartaruga Geochelone denticulata

    Directory of Open Access Journals (Sweden)

    M. A. TORSONI

    2002-11-01

    Full Text Available The hemolysate from Geochelone denticulata contains two main hemoglobin components, as shown by ion exchange chromatography and polyacrylamide gel electrophoresis (PAGE. Electrophoresis under dissociating conditions showed three types of globin chains. The apparent molecular mass, as determined by gel filtration on Sephadex G-200, was compatible with tetrameric Hb, which was unable to polymerize. The G. denticulata Hb has a P50 value of 9.56 mm Hg at pH 7.4. The Hb oxygenation appears to be under the control of organic phosphates and hydrogen ion since it is strongly affected by those species. In the presence ATP or IHP the P50 values increased to 29.51 mm Hg and 54.95 mm Hg, respectively, at pH 7.4. The n50 was generally lower than 1.5 in stripped Hb, suggesting a dissociation of tetramers. In the presence of organic phosphates n50 values increased to approximately 2.5. The Bohr effect was evident in oxygen equilibrium experiments. The hematocrit (32% and Hb concentration (5.7 mM as heme of G. denticulata blood were substantially larger than those of G. carbonaria, but the methemoglobin levels were similar in both species, approximately 1%. Thus, the oxygen capacity of blood appears to be higher in G. denticulata than in G. carbonaria, particularly considering the functional properties of their Hbs, which would guarantee the survival of animals.O hemolisado de Geochelone denticulata contém dois componentes principais, de acordo com a cromatografia de troca iônica e PAGE. Eletroforese sob condições dissociantes mostrou 3 tipos de cadeias de globina. A massa molecular aparente, determinada pela filtração em gel sobre Sephadex G-200, foi compatível com Hb tetramérica que foi incapaz de polimerizar. A Hb de G. denticulata tem valor de P50 de 9,56 mm Hg em pH 7,4. A oxigenação da Hb parece estar sob controle de fosfatos orgânicos e íons hidrogênio, uma vez que ela é fortemente afetada por essas espécies. Na presença de ATP ou IHP, os

  9. Co-inheritance of the rare β hemoglobin variants Hb Yaounde, Hb Görwihl and Hb City of Hope with other alterations in globin genes: impact in genetic counseling.

    Science.gov (United States)

    Vinciguerra, Margherita; Passarello, Cristina; Leto, Filippo; Cassarà, Filippo; Cannata, Monica; Maggio, Aurelio; Giambona, Antonino

    2015-04-01

    Nearly 1183 different molecular defects of the globin genes leading to hemoglobin variants have been identified (http://globin.bx.psu.edu) over the past decades. The purpose of this study was to report three cases, never described in the literature, of co-inheritance of three β hemoglobin variants with other alterations in globin genes and to evaluate the clinical significance to conduct an appropriate genetic counseling. We report the molecular study performed in three probands and their families, sampling during the screening program conducted at the Laboratory for Molecular Prenatal Diagnosis of Hemoglobinopathies at Villa Sofia-Cervello Hospital in Palermo, Italy. This work allowed us to describe the co-inheritance of three rare β hemoglobin variants with other alterations in globin genes: the β hemoglobin variant Hb Yaounde [β134(H12)Val>Ala], found for the first time in combination with ααα(anti3.7) arrangement, and the β hemoglobin variants Hb Görwihl [β5(A2)Pro>Ala] and Hb City of Hope [β69(E13)Gly>Ser], found both in association with β(0) -thalassemia. The present work emphasizes the importance of a careful evaluation of the hematological data, especially in cases of atypical hematological parameters, to carry out an adequate and complete molecular study and to formulate an appropriate genetic counseling for couples at risk. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  10. Hematological and Molecular Characterization of a Novel Hb A2 Variant with Homozygous α-Thalassemia-2 in a Southern Thai Individual.

    Science.gov (United States)

    Nuinoon, Manit; Jeenduang, Nutjaree; Kesornsit, Aumpika; Horpet, Dararat; Plyduang, Thunyaluk

    2017-05-01

    We report here the hematological and molecular features of a novel δ-globin chain variant found in a Southern Thai woman. Her complete blood count was as follows: red blood cell (RBC) count 5.90 × 10 12 /L, hemoglobin concentration (Hb) 12.6 g/dL, packed cell volume (PCV) 0.41 L/L, mean corpuscular volume (MCV) 69.5 fL, mean corpuscular Hb (MCH) 21.4 pg, mean corpuscular Hb concentration (MCHC) 30.7 g/dL and RBC distribution width (RDW) 13.1%. The blood smear demonstrated microcytic hypochromic RBCs suggestive of thalassemia trait. Hemoglobin analysis identified Hb A 2  + Hb A 2 -Kiriwong (2.4%) and Hb F (0.1%) on high performance liquid chromatography (HPLC). To characterize the α-thalassemia (α-thal) genotype, common α-thal-1 and α-thal-2 alleles were characterized by multiplex gap-polymerase chain reaction (gap-PCR). The results revealed homozygous α-thal-2 (-α 3.7 /-α 3.7 ) in this case. DNA sequencing showed the presence of a novel δ-globin gene mutation [δ77(EF1)His→Arg; HBD: c.233A>G] that we named Hb A 2 -Kiriwong for the village from where the proband lived. In summary, the presence of microcytic hypochromic RBCs in this case was likely the result of the homozygous -α 3.7 (rightward) deletion and was not affected by this Hb A 2 variant.

  11. Importância da avaliação da hemoglobina fetal na clínica da anemia falciforme The importance of the evaluation of fetal hemoglobin in the clinical assessment of sickle cell disease

    Directory of Open Access Journals (Sweden)

    Rita de Cassia Mousinho-Ribeiro

    2008-04-01

    Full Text Available A anemia falciforme está entre as doenças genéticas mais comuns e mais estudadas em todo o mundo. Ela é causada por mutação no gene β, produzindo alteração estrutural na molécula da hemoglobina. As moléculas de HbS, decorrentes da mutação, sofrem processo de polimerização fisiologicamente provocado pela baixa tensão de oxigênio, acidose e desidratação. Com isso, os eritrócitos passam a apresentar a forma de foice, causando vaso-oclusão e outras conseqüências. O objetivo desse estudo foi revisar a importância da hemoglobina fetal na clínica de pacientes portadores de anemia falciforme. O significado clínico da associação da elevação da hemoglobina fetal na anemia falciforme mostra-se favorável em termos hematológicos, pois, nessa interação, as células-F têm baixas concentrações de HbS e, com isso, inibem a polimerização da HbS e a alteração da morfologia dos eritrócitos. O tratamento com hidroxiuréia, em função do aumento na expressão da hemoglobina fetal que este fármaco proporciona, traz aos pacientes falcêmicos uma melhora significativa em sua clínica. Portanto, a hemoglobina fetal consiste no maior inibidor da polimerização da desoxi-HbS e, com isso, evita a falcização do eritrócito, a anemia hemolítica crônica, as crises dolorosas vaso-oclusivas, o infarto e a necrose em diversos órgãos, melhorando a clínica e a expectativa de vida dos pacientes.Sickle cell disease is one of the commonest and most studied genetic diseases in the world. Caused by a mutation of the β gene, it changes the molecular structure of hemoglobin. Abnormal Hb S molecules suffer polymerization physiologically provoked by a low oxygen tension, acidosis and dehydration. As a result, red blood cells take on a sickle cell form, which causes microvascular occlusion with varying consequences. The objective of this study was to review the importance of fetal hemoglobin in the clinical assessment of sickle cell

  12. Phenotypic Diversity of Sickle Cell Disease in Patients with a Double Heterozygosity for Hb S and Hb D-Punjab.

    Science.gov (United States)

    Torres, Lidiane S; Okumura, Jéssika V; Belini-Júnior, Édis; Oliveira, Renan G; Nascimento, Patrícia P; Silva, Danilo G H; Lobo, Clarisse L C; Oliani, Sonia M; Bonini-Domingos, Claudia R

    2016-09-01

    Phenotypic heterogeneity for sickle cell disease is associated to several genetic factors such as genotype for sickle cell disease, β-globin gene cluster haplotypes and Hb F levels. The coinheritance of Hb S (HBB: c.20A > T) and Hb D-Punjab (HBB: c.364G > C) results in a double heterozygosity, which constitutes one of the genotypic causes of sickle cell disease. This study aimed to assess the phenotypic diversity of sickle cell disease presented by carriers of the Hb S/Hb D-Punjab genotype and the Bantu [- + - - - -] haplotype. We evaluated medical records from 12 patients with sickle cell disease whose Hb S/Hb D-Punjab genotype and Bantu haplotype were confirmed by molecular analysis. Hb S and Hb D-Punjab levels were quantified by chromatographic analysis. Mean concentrations of Hb S and Hb D-Punjab were 44.8 ± 2.3% and 43.3 ± 1.8%, respectively. Painful crises were present in eight (66.7%) patients evaluated, representing the most common clinical event. Acute chest syndrome (ACS) was the second most prevalent manifestation, occurring in two individuals (16.7%). Three patients were asymptomatic, while another two exhibited greater diversity of severe clinical manifestations. Medical records here analyzed reported a significant clinical diversity in sickle cell disease ranging from the absence of symptoms to wide phenotypic variety. The sickle cell disease genotype, Bantu haplotype and hemoglobin (Hb) levels did not influence the clinical diversity. Thus, we concluded that the phenotypic variation in sickle cell disease was present within a specific genotype for disease regardless of the β-globin gene cluster haplotypes.

  13. Stat5 phosphorylation is responsible for the excessive potency of HB-EGF.

    Science.gov (United States)

    Heo, Jeongyeon; Kim, Jae Geun; Kim, Sunghwan; Kang, Hara

    2017-12-23

    Heparin-binding EGF-like growth factor (HB-EGF) is a potent growth factor involved in wound healing and tumorigenesis. Despite the sequence similarity between HB-EGF and EGF, HB-EGF induces cellular proliferation and migration more potently than EGF. However, the differential regulation by HB-EGF and EGF has not been thoroughly elucidated. In this study, we compared signaling pathways activated by HB-EGF and EGF to understand the details of the molecular mechanism of the high potency induced by HB-EGF. HB-EGF specifically induced the phosphorylation of EGFR-Y1045 and activated Stat5, which is responsible for promoting cell proliferation, and migration. The competition of phosphorylated EGFR-Y1045 inhibited Stat5 activation and consequently lowered the effect of HB-EGF on cell proliferation, suggesting that the phosphorylation of EGFR-Y1045 is essential for the activation of Stat5. The phosphorylation of EGFR-Y1045 and Stat5 induced by HB-EGF was prevented by sequestering the heparin-binding domain, suggesting that the heparin-binding domain is critical for HB-EGF-mediated signaling and cellular responses. In conclusion, the heparin-binding domain of HB-EGF was responsible for EGFR-mediated Stat5 activation, resulting in a more potent cellular proliferation, and migration than that mediated by EGF. This molecular mechanism is useful for understanding ligand-specific EGFR signaling and developing biomedicines for wound healing or cancer therapy. © 2017 Wiley Periodicals, Inc.

  14. Effects of hemoglobin variants HbJ Bangkok, HbE, HbG Taipei, and HbH on analysis of glycated hemoglobin via ion-exchange high-performance liquid chromatography.

    Science.gov (United States)

    Zhang, Xiu-Ming; Wen, Dong-Mei; Xu, Sheng-Nan; Suo, Ming-Huan; Chen, Ya-Qiong

    2018-01-01

    To explore the effects of HbJ Bangkok, HbE, HbG Taipei, and α-thalassemia HbH on the results of HbA1c assessment using ion-exchange high-performance liquid chromatography (IE-HPLC). We enrolled five patients in which the results of the IE-HPLC HbA1c assay were inconsistent with the average levels of FBG. We performed hemoglobin capillary (Hb) electrophoresis using whole-blood samples. We also sequenced the genes encoding Hb using dideoxy-mediated chain termination and analyzed HbA1c using borate affinity HPLC (BA-HPLC) and turbidimetric inhibition immunoassay (TINIA). Two patients had the HbJ Bangkok variant. Hb genotypes of these patients were β 41-42 /β J Bangkok and β N /β J Bangkok , and the content of HbJ Bangkok was 93.9% and 52.4%, respectively. The remaining three patients had the following: HbE (β N /β E Hb genotype, 23.6% HbE content), HbG Taipei (β N /β G Taipei Hb genotype, 39.4% HbG Taipei content), and α-thalassemia HbH (6.1% HbH content, 2.8% Hb Bart's content). In the patients with β-thalassemia and HbJ Bangkok variants, the presence of the variants interfered with the results of HbA1c analyses using IE-HPLC and TINIA; in the remaining four patients, there was interference with the results of HbA1c IE-HPLC but not with the TINIA assay. There was no interference with BA-HPLC HbA1c results. HbJ Bangkok, HbE, HbG Taipei Hb, and α-thalassemia HbH disease cause varying degrees of interference with the analysis of HbA1c using IE-HPLC. In these patients, we suggest using methods free from such interference for the analysis of HbA1c and other indicators to monitor blood glucose levels. © 2017 Wiley Periodicals, Inc.

  15. α-Thalassemia Associated with Hb Instability: A Tale of Two Features. The Case of Hb Rogliano or α1 Cod 108(G15)Thr→Asn and Hb Policoro or α2 Cod 124(H7)Ser→Pro.

    Science.gov (United States)

    Musollino, Gennaro; Cardiero, Giovanna; Flagiello, Angela; La Porta, Gaetana; Lagona, Laura; Prezioso, Romeo; Qualtieri, Gabriele; Gaudiano, Carlo; Medulla, Emilia; Merlino, Antonello; Pucci, Piero; Lacerra, Giuseppina

    2015-01-01

    We identified two new variants in the third exon of the α-globin gene in families from southern Italy: the Hb Rogliano, α1 cod108 ACC>AAC or α1[α108(G15)Thr→Asn] and the Hb Policoro, α2 cod124 TCC>CCC or α2[α124(H7)Ser→Pro]. The carriers showed mild α-thalassemia phenotype and abnormal hemoglobin stability features. These mutations occurred in the G and H helices of the α-globin both involved in the specific recognition of AHSP and β1 chain. Molecular characterization of mRNA, globin chain analyses and molecular modelling studies were carried out to highlight the mechanisms causing the α-thalassemia phenotype. The results demonstrated that the α-thalassemia defect associated with the two Hb variants originated by different defects. Hb Rogliano showed an intrinsic instability of the tetramer due to anomalous intra- and inter-chain interactions suggesting that the variant chain is normally synthesized and complexed with AHSP but rapidly degraded because it is unable to form the α1β1 dimers. On the contrary in the case of Hb Policoro two different molecular mechanisms were shown: the reduction of the variant mRNA level by an unclear mechanism and the protein instability due to impairment of AHSP interaction. These data highlighted that multiple approaches, including mRNA quantification, are needed to properly identify the mechanisms leading to the α-thalassemia defect. Elucidation of the specific mechanism leads to the definition of a given phenotype providing important guidance for the diagnosis of unstable variants. PMID:25730315

  16. Bio-plastic (P-3HB-co-3HV) from Bacillus circulans (MTCC 8167) and its biodegradation.

    Science.gov (United States)

    Phukon, Pinkee; Saikia, Jyoti Prasad; Konwar, Bolin Kumar

    2012-04-01

    Polyhydroxyalkanoates (PHAs) are naturally occurring polyesters synthesized by bacteria for carbon and energy storage and it has commercial potential as bioplastic. The bacterial species Bacillus circulans MTCC 8167, isolated from crude oil contaminated soil, can efficiently produce medium chain length polyhydroxyalkanoates (P-3HB-co-3HV) from cheap carbon sources like dextrose. The molecular mass of P-3HB-co-3HV was reported as 5.1×10(4)Da with polydispersity index of 1.21 by gel permeation chromatography. In the present investigation different bacteria and fungi species were used for testing the biodegradability of the extracted polymer. The FTIR spectra of the biodegraded PHBV film showed a decrease in the peak from 1735 cm(-1) (untreated film) to 1675 cm(-1), and disappearance of a peak present in the control at 2922 cm(-1) indicating the breakdown of ester (>C=O) or O-R group and -C=H bond, respectively. From biodegradability testing, the tested microorganisms were found to have decisive contribution to the biodegradation of P-3HB-co-3HV polymer. Copyright © 2011 Elsevier B.V. All rights reserved.

  17. Characterization of Hb Lepore variants in the UK population.

    Science.gov (United States)

    Guo, Lina; Kausar, Anika; Old, John M; Henderson, Shirley J; Gallienne, Alice E

    2015-01-01

    A molecular study of Hb Lepore heterozygotes identified by the UK population screening program has revealed four out of the five known Lepore variants. The region of homologous δ- and β-globin gene sequence was determined in 58 unrelated Hb Lepore heterozygotes referred for confirmation of their carrier status by DNA analysis through the national thalassemia and sickle cell screening program over a period of 10 years. The most common variant found was Hb Lepore-Boston-Washington (Hb LBW, HBD: c.265 C > c.315 + 7 C) observed in 46 carriers (79.0%). Hb Lepore-Hollandia (HBD: c.69 A > c.92 + 16 A) was found in nine cases (16.0%); Hb Lepore-Baltimore (HBD: c.208 G > c.254 C) in two cases (4.0%) and Hb Lepore-ARUP (HBD: c.97 C > c.150 C) in one carrier (2.0%). Analysis of the hematological findings showed no significant differences between the four groups. The wide range of Hb Lepore variants observed in this study confirms the very diverse range of α- and β-globin gene mutations observed in the UK population by previous studies.

  18. The optical emission from the supernova remnant HB 3

    Science.gov (United States)

    Fesen, R. A.; Gull, T. R.

    1983-01-01

    The supernova remnant HB 3 was first detected as a radio source by Brown and Hazard (1953). On the basis of subsequent radio studies, it was concluded that the object was a supernova remnant (SNR). HB 3 is located at the far western edge of the H II region/molecular cloud complex W3-W4-W5 (IC 1795-1805-1848). However, a physical association of HB 3 with this complex is uncertain. In the present investigation, attention is called to the probability that HB 3 exhibits a more extensive optical emission structure than previously realized, and one which agrees well with both the position and morphology of the radio emission. It is found that narrow-passband optical images strongly suggest an almost complete optical emission shell for HB 3. Spectroscopic observations are, however, required to confirm that this emission is characteristic of a SNR.

  19. Molecular characterization of HbEREBP2, a jasmonateresponsive ...

    African Journals Online (AJOL)

    Transcription factors of AP2/ERF superfamily are generally involved in defense responses of plants to biotic and abiotic stresses. Although, defense proteins are present in abundance in laticifers of rubber tree, little is known about their transcriptional regulation. In this study, a full length cDNA, referred to as HbEREBP2 was ...

  20. Interaction of Hb Grey Lynn (Vientiane) [α91(FG3)Leu>Phe (α1)] with Hb E [β26(B8) Glu>Lys] and α(+)-thalassemia: Molecular and Hematological Analysis.

    Science.gov (United States)

    Singha, Kritsada; Fucharoen, Goonnapa; Fucharoen, Supan

    2015-01-01

    Hemoglobin (Hb) Grey Lynn is a Hb variant caused by a mutation at codon 91 of α1-globin gene whereas Hb E is a common β-globin chain variant among Southeast Asian population. We report two hitherto undescribed conditions of Hb Grey Lynn found in Thai individuals. The study was done on two unrelated Thai subjects. Hematological parameters were recorded and Hb analysis was carried out using automated Hb analyzers. Mutations were identified by DNA analysis. Hematological features of the patients were compared with those of various forms of Hb Grey Lynn documented previously. Hb and DNA analyses identified a heterozygous Hb Grey Lynn in one patient and a double heterozygous Hb Grey Lynn and Hb E with α(+)-thalassemia in another. Interaction of α(Grey Lynn) with β(E) chains leads to the formation of a new Hb variant, namely the Hb Grey Lynn E (α(GL)2β(E)2), detectable by liquid chromatography (10.3%) but masked by Hb E on capillary electrophoresis. Interaction of these multiple globin gene defects could lead to complex hemoglobinopathies requiring combined analysis with multiple Hb analyzers followed by DNA testing to provide accurate diagnosis of the cases.

  1. Comparison of the characteristics of two hemoglobin variants, Hb D-Iran and Hb E, eluting in the Hb A2 window.

    Science.gov (United States)

    Dass, Jasmita; Gupta, Aastha; Mittal, Suchi; Saraf, Amrita; Langer, Sabina; Bhargava, Manorama

    2017-06-01

    Cation exchange-high performance liquid chromatography (CE-HPLC) is most commonly used to evaluate hemoglobin (Hb) variants, which elute in the Hb A2 window. This study aimed to assess prevalence of an uncommon Hb variant, Hb D-Iran, and compare its red cell parameters and peak characteristics with those of Hb E that commonly elutes in the Hb A2 window. Generally, we assess abnormal Hb using CE-HPLC as the primary technique along with alkaline and acid electrophoresis. All cases with Hb A2 window >9%, as assessed by CE-HPLCs during 2009-2013, were selected. Twenty-nine cases with Hb D-Iran variant were identified-25 heterozygous, 2 homozygous, 1 compound heterozygous Hb D-Iran/β-thalassemia, and 1 Hb D-Iran/Hb D-Punjab. Overall prevalence of Hb D-Iran was 0.23%. Compared to patients with Hb E, those with Hb D-Iran had significantly higher Hb (12.1 vs. 11.3 g/dL, P =0.03), MCV (82.4 vs. 76.4 fL, P =0.0044), MCH (27.9 vs. 25.45 pg, P =0.0006), and MCHC (33.9 vs. 33.3 g/dL, P =0.0005). Amount of abnormal Hb (40.7 vs. 26.4%, P =0.0001) was significantly higher while retention time (3.56 vs. 3.70 min, P =0.0001) was significantly lower in Hb D-Iran than in Hb E. Hb D-Iran peak can be easily missed if area and retention time of the Hb A2 window are not carefully analyzed. To distinguish between variants, careful analysis of peak area and retention time is sufficient in most cases and may be further confirmed by the second technique-alkaline electrophoresis.

  2. Polimorfismo genético da glicose-6-fosfato desidrogenase na população da região de Araraquara, Estado de São Paulo

    Directory of Open Access Journals (Sweden)

    Rosecler Inácia de Paula Ferreira

    2014-08-01

    Full Text Available A importância da enzima Glicose-6-fosfato desidrogenase (G6PD no metabolismo eritrocitário está na obtenção de energia calórica e redutora para a proteção celular contra agressões oxidativas. A deficiência de G6PD é a eritroenzimopatia que causa mais frequentemente anemia hemolítica, com mais de 130 variantes moleculares identificadas. O objetivo deste estudo foi realizar a análise molecular da deficiência de G6PD em uma população masculina adulta da região de Araraquara, SP, para a identificação das mutações genéticas. Nos 5087 doadores de sangue do sexo masculino pesquisados, foram encontrados 89 deficientes de G6PD, confirmados pela determinação da atividade enzimática e eletroforese em acetato de celulose, com frequência de 1,75%, valores semelhantes aos encontrados por outros pesquisadores no Estado de São Paulo. A análise molecular realizada pela amplificação do DNA genômico com iniciadores específicos e digestão com enzimas de restrição, demonstrou que 96,6% dos deficientes apresentaram a variante G6PD A¯, com as mutações 376(A→G e 202(G→A e atividade enzimática média de 1,31 UI.g de Hb-1.min-1 a 37º C, correspondendo a 10,8% da atividade enzimática da enzima normal G6PD B. Não foram encontradas as formas variantes G6PD A¯ 680(G→T e 968(T→C. Em 3,4% dos indivíduos deficientes, foi encontrada a variante G6PD Mediterrânea, mutação 563(C→T e atividade enzimática média de 0,25 UI.g de Hb-1.min-1 a 37ºC, correspondendo a 2,1% da atividade enzimática da G6PD B. A utilização das técnicas tradicionais, aliadas à identificação da variante molecular, são importantes na compreensão das propriedades estruturais, funcionais e comportamento hemolítico dos glóbulos vermelhos do paciente.

  3. HbD Punjab/HbQ India compound heterozygosity: An unusual association.

    Directory of Open Access Journals (Sweden)

    Stacy Colaco

    2014-11-01

    Full Text Available Background: Haemoglobinopathies are the commonest hereditary disorders in India and pose a major health problem. Both beta thalassaemia and structural haemoglobin variants are relatively common in north western India. Here we report a 29 year old Sindhi female who was referred to us for a haemoglobinopathy work up and genetic counseling since her spouse was a classical beta thalassaemia carrier. Method: A complete blood count was done on an automated cell counter. Haemoglobin analysis was carried out using HPLC Variant Haemoglobin Testing System.  The cellulose acetate electrophoresis was carried out [pH 8.9]. Confirmation of mutations was done by automated DNA sequencing. Results: HPLC analysis showed four major peaks, HbA0, a peak in the HbD window, an unknown peak [retention time 4.74 minutes] and a peak in the HbC window. The HbA2 level was 2.2% and the HbF level was 0.7%.Cellulose acetate electrophoresis at alkaline pH, a slow moving band was seen at the HbS/D position along with a prominent band at the HbA2 position. DNA sequencing of the β and α genes showed presence of the 2 hemoglobin variants :Hb D [b 121GAA à CAA] and Hb Q [a 64 AAG à GAG]. The δ globin gene was normal. The additional peak in the HbC window was due to the formation of a heterodimer hybrid. Conclusion: Both HbD Punjab and HbQ India are relatively common in India but their co-inheritance has not been described in the country. This is the second report of compound heterozygosity for HbQ India/HbD Punjab haemoglobinopathy globally, and the first one from India.

  4. The Properties of Red Blood Cells from Patients Heterozygous for HbS and HbC (HbSC Genotype

    Directory of Open Access Journals (Sweden)

    A. Hannemann

    2011-01-01

    Full Text Available Sickle cell disease (SCD is one of the commonest severe inherited disorders, but specific treatments are lacking and the pathophysiology remains unclear. Affected individuals account for well over 250,000 births yearly, mostly in the Tropics, the USA, and the Caribbean, also in Northern Europe as well. Incidence in the UK amounts to around 12–15,000 individuals and is increasing, with approximately 300 SCD babies born each year as well as with arrival of new immigrants. About two thirds of SCD patients are homozygous HbSS individuals. Patients heterozygous for HbS and HbC (HbSC constitute about a third of SCD cases, making this the second most common form of SCD, with approximately 80,000 births per year worldwide. Disease in these patients shows differences from that in homozygous HbSS individuals. Their red blood cells (RBCs, containing approximately equal amounts of HbS and HbC, are also likely to show differences in properties which may contribute to disease outcome. Nevertheless, little is known about the behaviour of RBCs from HbSC heterozygotes. This paper reviews what is known about SCD in HbSC individuals and will compare the properties of their RBCs with those from homozygous HbSS patients. Important areas of similarity and potential differences will be emphasised.

  5. Effects of TT8 and HB12 Silencing on the Relations between the Molecular Structures of Alfalfa ( Medicago sativa) Plants and Their Nutritional Profiles and In Vitro Gas Production.

    Science.gov (United States)

    Lei, Yaogeng; Hannoufa, Abdelali; Prates, Luciana Louzada; Shi, Haitao; Wang, Yuxi; Biligetu, Bill; Christensen, David; Yu, Peiqiang

    2018-06-06

    The objective of this study was to investigate the effects of silencing the TT8 and HB12 genes on the nutritive profiles and in vitro gas production of alfalfa in relation to the spectral molecular structures of alfalfa. TT8-silenced (TT8i, n = 5) and HB12-silenced (HB12i, n = 11) alfalfa were generated by RNA interference (RNAi) and grown with nontransgenic wild type controls (WT, n = 4) in a greenhouse. Alfalfa plants were harvested at early-to-mid vegetative stage. Samples were analyzed for their chemical compositions, CNCPS fractions, and in vitro gas production. Correlations and regressions of the nutritional profiles and in vitro gas production with the molecular spectral structures were also determined. The results showed that the transformed alfalfa had higher digestible fiber and lower crude protein with higher proportions of indigestible protein than WT. HB12 RNAi had lower gas production compared with those of the others. Some chemical, CNCPS, and gas-production profiles were closely correlated with spectral structures and could be well predicted from spectral parameters. In conclusion, the RNAi silencing of TT8 and HB12 in alfalfa altered the chemical, CNCPS and gas-production profiles of alfalfa, and such alterations were closely correlated with the inherent spectral structures of alfalfa.

  6. Stability study for magnetic reagent assaying Hb and HbA1c

    International Nuclear Information System (INIS)

    Hsieh, Wen-Pin; Chieh, J.J.; Yang, C.C.; Yang, S.Y.; Chen, Po-Yu; Huang, Yu-Hao; Hong, Y.W.; Horng, H.E.

    2013-01-01

    Reagents for magnetically labeled immunoassay on human Hb and human HbA1c have been synthesized. The reagents consist of Fe 3 O 4 magnetic particles biofunctionalized with antibodies against Hb and HbA1c. It has been demonstrated that the reagents can be applied to quantitatively detect Hb and HbA1c by using immunomagnetic reduction assay. In addition to characterizing the assay properties, such as the standard curve and the low-detection limit, the stability of reagents is investigated. To do this, the temporal dependence of particle sizes and the bio-activity of reagents are monitored. The results show that the reagents are highly stable when stored at 2–8 °C. This means that the reagents synthesized in this work are promising for practical applications. - Highlights: ► The properties of assaying Hb and HbA1c using immunomagnetic reduction are studied. ► The magnetic nanoparticles with antibodies are highly stable in solutions. ► No significant mutual interference between Hb and HbA1c in assays is observed. ► High-sensitivity assays on Hb and HbA1c using immunomagnetic reduction are achieved.

  7. Polimorfismo da hemoglobina de bubalinos (Bubalis bubalis da raça Murrah criados no Estado de São Paulo, Brasil

    Directory of Open Access Journals (Sweden)

    A. M. F. Rosenfeld

    2006-03-01

    Full Text Available Os tipos de hemoglobina foram determinados em 41 amostras de sangue de bubalinos sadios da raça Murrah, criados no município de Roseira, no Estado de São Paulo, sendo cinco animais machos e 36 fêmeas. As amostras sangüíneas foram colhidas por venipunção da jugular, em tubos contendo EDTA e a determinação dos tipos de hemoglobina foi realizada pela técnica de eletroforese alcalina em acetato de celulose, utilizando-se o Tris-EDTA-Borato (pH 8,6 como solução tampão. Duas bandas de migração relativas aos alelos HbA e HbB foram observadas, identificando-se dois genótipos Hb-AA e Hb-AB e as suas freqüências na população avaliada foram: 95,1% dos bubalinos apresentaram o tipo heterozigoto Hb-AB e 4,9% o tipo homozigoto Hb-AA. O polimorfismo da hemoglobina foi observado nos bubalinos e o genótipo heterozigoto Hb-AB foi o mais freqüente.

  8. Stability study for magnetic reagent assaying Hb and HbA1c

    Energy Technology Data Exchange (ETDEWEB)

    Hsieh, Wen-Pin [Actherm Inc., Hsinchu 200, Taiwan (China); Chieh, J.J.; Yang, C.C. [Institute of Electro-optical Science and Technology, National Taiwan Normal University, Taipei 116, Taiwan (China); Yang, S.Y. [Institute of Electro-optical Science and Technology, National Taiwan Normal University, Taipei 116, Taiwan (China); MagQu Co., Ltd., Sindian Dist., New Taipei City 231, Taiwan (China); Chen, Po-Yu; Huang, Yu-Hao [Actherm Inc., Hsinchu 200, Taiwan (China); Hong, Y.W. [Institute of Electro-optical Science and Technology, National Taiwan Normal University, Taipei 116, Taiwan (China); Horng, H.E., E-mail: phyfv001@ntnu.edu.tw [Institute of Electro-optical Science and Technology, National Taiwan Normal University, Taipei 116, Taiwan (China)

    2013-01-15

    Reagents for magnetically labeled immunoassay on human Hb and human HbA1c have been synthesized. The reagents consist of Fe{sub 3}O{sub 4} magnetic particles biofunctionalized with antibodies against Hb and HbA1c. It has been demonstrated that the reagents can be applied to quantitatively detect Hb and HbA1c by using immunomagnetic reduction assay. In addition to characterizing the assay properties, such as the standard curve and the low-detection limit, the stability of reagents is investigated. To do this, the temporal dependence of particle sizes and the bio-activity of reagents are monitored. The results show that the reagents are highly stable when stored at 2-8 Degree-Sign C. This means that the reagents synthesized in this work are promising for practical applications. - Highlights: Black-Right-Pointing-Pointer The properties of assaying Hb and HbA1c using immunomagnetic reduction are studied. Black-Right-Pointing-Pointer The magnetic nanoparticles with antibodies are highly stable in solutions. Black-Right-Pointing-Pointer No significant mutual interference between Hb and HbA1c in assays is observed. Black-Right-Pointing-Pointer High-sensitivity assays on Hb and HbA1c using immunomagnetic reduction are achieved.

  9. Dynamics of α-Hb chain binding to its chaperone AHSP depends on heme coordination and redox state.

    Science.gov (United States)

    Kiger, Laurent; Vasseur, Corinne; Domingues-Hamdi, Elisa; Truan, Gilles; Marden, Michael C; Baudin-Creuza, Véronique

    2014-01-01

    AHSP is an erythroid molecular chaperone of the α-hemoglobin chains (α-Hb). Upon AHSP binding, native ferric α-Hb undergoes an unprecedented structural rearrangement at the heme site giving rise to a 6th coordination bond with His(E7). Recombinant AHSP, WT α-Hb:AHSP and α-Hb(HE7Q):AHSP complexes were expressed in Escherichia coli. Thermal denaturation curves were measured by circular dichroism for the isolated α-Hb and bound to AHSP. Kinetics of ligand binding and redox reactions of α-Hb bound to AHSP as well as α-Hb release from the α-Hb:AHSP complex were measured by time-resolved absorption spectroscopy. AHSP binding to α-Hb is kinetically controlled to prevail over direct binding with β-chains and is also thermodynamically controlled by the α-Hb redox state and not the liganded state of the ferrous α-Hb. The dramatic instability of isolated ferric α-Hb is greatly decreased upon AHSP binding. Removing the bis-histidyl hexacoordination in α-HbH58(E7)Q:AHSP complex reduces the stabilizing effect of AHSP binding. Once the ferric α-Hb is bound to AHSP, the globin can be more easily reduced by several chemical and enzymatic systems compared to α-Hb within the Hb-tetramer. α-Hb reduction could trigger its release from AHSP toward its final Hb β-chain partner producing functional ferrous Hb-tetramers. This work indicates a preferred kinetic pathway for Hb-synthesis. The cellular redox balance in Hb-synthesis should be considered as important as the relative proportional synthesis of both Hb-subunits and their heme cofactor. The in vivo role of AHSP is discussed in the context of the molecular disorders observed in thalassemia. © 2013 Elsevier B.V. All rights reserved.

  10. HbQ-India associated with microcytosis: An uncommon hemoglobin variant associated with a common hematologic condition

    Directory of Open Access Journals (Sweden)

    Amit Kumar Yadav

    2010-09-01

    Full Text Available HbQ-India is a rare alpha chain variant that usually presents in the heterozygous state. Normally, HbQ-India is clinically silent. It becomes symptomatic when present in association with other conditions. We report a case of HbQ-India with concomitant presence of iron deficiency anemia. A 16-year-old female presented with weakness and pallor intermittently for six years. Complete blood count showed severe microcytic hypochromic anemia. Hemoglobin electrophoresis showed a prominent band in the S,D,G region. Tests for sickling were negative. High performance liquid chromatography (HPLC showed a peak in the unknown window (4.70-4.90 min suggestive of HbQ-India. Serum iron profile was suggestive of iron deficiency anemia. Based on the above findings, a diagnosis of coexistent HbQ-India–iron deficiency anemia was made. A family study revealed the father as having moderate anemia with similar findings while the mother was normal. Abnormal hemoglobin in the patient was confirmed by molecular diagnosis.HbQ variants are the alpha globin chain variants due to structural mutations (α64 Asp→His inherited in autosomal dominant fashion. Three molecular variant types have been documented, namely HbQ-India, HbQ-Thailand and HbQ-Iran. Normally, HbQ is clinically silent. Therefore, careful screening of the samples using routine techniques like Hb electrophoresis and HPLC are needed for identification of such abnormal hemoglobin variants like HbQ-India.

  11. Haemoglobin polimorphism in sheep (“Ovis aries”, L.: evaluation of genotype and frequency of animals breeder in Bahia State, Brazil Polimorfismo da hemoglobina de ovinos ("Ovis aries", L.: determinação do tipo e da freqüência em animais criados no Estado da Bahia

    Directory of Open Access Journals (Sweden)

    Adriana da Silva Rodrigues Cavacanti

    2009-09-01

    Full Text Available The distribution of hemoglobin types was investigated in 296 blood samples of health sheep, included adult and young animal, breeder in Bahia State. In this study were included sheep of the Brazilian Native breed (BNB as Santa Inês (SI, Morada Nova (MN, Rabo Largo (RL and crossbred of Suffolk x Dorper and BNB x Dorper. Blood samples were collected by venipuncture of the jugular in tubes containing E.D.T.A. and the hemoglobin typing was performed by starch gel electrophoresis using Tris-EDTA-Borate (pH 9,5 as buffer solution. Two migrations bands associated to allele HbA and HbB were found, corresponding to the three genotypes: Hb-AA, Hb-AB and Hb-BB and the frequencies if the type observed were: Hb-AA 49,0% (145/296, Hb-AB 39,18% (116/296 e Hb-BB 11,82% (35/296. The sheep of the NBB (SI, RL and MN were found all Hb types identifield; in the Dorper breed only Hb-AA was observed and in the crossbreed wasn’t detected the Hb-BB. The gene frequency of the allelic HbA and HbB were, respectively 0,69 and 0,31. The fetal haemoglobin was no longer detectable in any sheep. The hemoglobin polymorphism occurred among the sheep being the homozygous genotypes Hb-AA predominant.Os tipos da hemoglobina de ovinos foram determinados colhendo-se 296 amostras de sangue de animais de raças criadas no Estado da Bahia, que incluiu machos e fêmeas; adultos e jovens. Foram utilizados ovinos das raças nativas Santa Inês (SI, Morada Nova (MN, Rabo Largo (RL, Dorper, de origem africana, bem como animais resultantes de cruzamento entre as raças nativas com a raça Suffolk e com a raça africana. As amostras sangüíneas foram colhidas por venipunção da jugular, em tubos contendo EDTA e a determinação dos tipos de hemoglobina foi realizada por meio da técnica de eletroforese alcalina em gel (pH 9,5. Dessas amostras avaliadas foram identificados três genótipos da hemoglobina: Hb-AA, caracterizada por uma banda lenta; Hb-BB, caracterizada pela presença da banda

  12. Cation Homeostasis in Red Cells From Patients With Sickle Cell Disease Heterologous for HbS and HbC (HbSC Genotype

    Directory of Open Access Journals (Sweden)

    A. Hannemann

    2015-11-01

    Full Text Available Sickle cell disease (SCD in patients of HbSC genotype is considered similar, albeit milder, to that in homozygous HbSS individuals — but with little justification. In SCD, elevated red cell cation permeability is critical as increased solute loss causes dehydration and encourages sickling. Recently, we showed that the KCl cotransporter (KCC activity in red cells from HbSC patients correlated significantly with disease severity, but that in HbSS patients did not. Two transporters involved in red cell dehydration, the conductive channels Psickle and the Gardos channel, behaved similarly in red cells from the two genotypes, but were significantly less active in HbSC patients. By contrast, KCC activity was quantitatively greater in HbSC red cells. Results suggest that KCC is likely to have greater involvement in red cell dehydration in HbSC patients, which could explain its association with disease severity in this genotype. This work supports the hypothesis that SCD in HbSC patients is a distinct disease entity to that in HbSS patients. Results suggest the possibility of designing specific treatments of particular benefit to HbSC patients and a rationale for the development of prognostic markers, to inform early treatment of children likely to develop more severe complications of the disease.

  13. A targetable HB-EGF-CITED4 axis controls oncogenesis in lung cancer.

    Science.gov (United States)

    Hsieh, C-H; Chou, Y-T; Kuo, M-H; Tsai, H-P; Chang, J-L; Wu, C-W

    2017-05-25

    Aberrant epidermal growth factor (EGF) receptor (EGFR) signaling contributes to neoplastic initiation and progression in lung. Mutated EGFR has become as an important therapeutic target in lung cancer, whereas targeted treatment is not available for wild-type EGFR or its ligands. In this study, we found that heparin-binding (HB)-EGF, a member of the EGF family, was highly expressed in a subset of lung cancer, proliferation of which was dependent on HB-EGF signaling. Silencing of HB-EGF with RNA interference inhibited cell cycle progression in lung cancer cells. We observed that, upon HB-EGF induction, CITED4 was induced through a signal transducer and activator of transcription 3 (STAT3)-dependent pathway, regulating cell proliferation. CITED4 interacted with MYC and potentiated MYC-mediated transactivation of the CCND1 promoter, leading to cell cycle progression. Correlation analysis revealed that HB-EGF and CITED4 were significantly positively associated in primary lung tumors, and expression of HB-EGF predicted a poor survival outcome in patients. In vitro and in vivo experiments revealed that pharmacological inhibition of HB-EGF with CRM197 significantly attenuated tumor cell growth. Thus, CITED4 functions as a molecular switch in HB-EGF-induced growth control, and HB-EGF provides a novel therapeutic target for lung cancer intervention.

  14. Hb taradale [beta82(EF6)Lys-->Arg]: a novel mutation at a 2,3-diphosphoglycerate binding site.

    Science.gov (United States)

    Brennan, Stephen O; Sheen, Campbell; Chan, Tim; George, Peter M

    2005-01-01

    Hb Taradale [beta82(EF6)Lys-->Arg] was initially detected as a split Hb A0 peak on Hb A1c, monitoring. Red cell parameters, hemoglobin (Hb) electrophoresis and stability tests were normal. Mass spectrometry (ms) clearly identified a variant beta chain with a mass increase of 28 Da and peptide mapping located the mutation site to peptide betaT-9. DNA sequencing confirmed the presence of a novel beta82(EF6)Lys-->Arg mutation. This conservative substitution at a 2,3-diphosphoglycerate (2,3-DPG) binding site did not, however, appear to affect the P50 for oxygen binding.

  15. Hb variants in Korea: effect on HbA1c using five routine methods.

    Science.gov (United States)

    Yun, Yeo-Min; Ji, Misuk; Ko, Dae-Hyun; Chun, Sail; Kwon, Gye Cheol; Lee, Kyunghoon; Song, Sang Hoon; Seong, Moon Woo; Park, Sung Sup; Song, Junghan

    2017-07-26

    Quantification of glycated hemoglobin (HbA1c) is a challenge in patients with hemoglobin (Hb) variants. We evaluated the impact of various Hb variants on five routine HbA1c assays by comparing with the IFCC reference measurement procedure (RMP). Whole blood samples showing warning flags or no results on routine HPLC HbA1c assays were confirmed for Hb variants and were submitted to HbA1c quantification using Sebia Capillarys 2 Flex Piercing, Roche Tina-quant HbA1c Gen. 2, Bio-Rad Variant II Turbo 2.0, ADAMS HA-8180, Tosoh G8 standard mode, and IFCC RMP using LC-MS. Among 114 samples, the most common variants were Hb G-Coushatta (n=47), Queens (n=41), Ube-4 (n=11), Chad (n=4), Yamagata (n=4), G-His-Tsou (n=2), G-Taipei (n=1), Fort de France (n=1), Hoshida (n=1), and two novel variants (Hb α-globin, HBA 52 Gly>Cys and Hb β-globin, HBB 146 His>Asn). In terms of control samples, all the result of HbA1c were "acceptable", within the criteria of ±7% compared to IFCC RMP target values. However, percentage of "unacceptable" results of samples with Hb variants were 16% for Capillarys 2, 7% for Tina-quant, 51% for Variant II Turbo 2.0, 95% for G8 standard mode, and 89% for HA-8180. The Capillarys 2 and HA-8180 assay did not provide the results in 5 and 40 samples with Hb variants, respectively. HbA1c results from five routine assays in patients with relatively common Hb variants in Korea showed various degrees of bias compared to those of IFCC RMP. Therefore, laboratories should be aware of the limitation of their methods with respect to interference from Hb variants found commonly in their local population and suggest an alternative HbA1c quantification method.

  16. First Cases of Hb Agrinio Described in Patients from the Republic of Macedonia.

    Science.gov (United States)

    Dimishkovska, Marija; Kuzmanovska, Maja; Kocheva, Svetlana; Martinova, Kata; Karanfilski, Oliver; Stojanoski, Zlate; Plaseska-Karanfilska, Dijana

    Previous molecular analyses of α-thalassemia (α-thal) in the Republic of Macedonia have identified the following genetic defects: -α 3.7 (rightward), -(α) 20.5 and - - MED I deletions and Hb Icaria [α142, Term→Lys (α2), HBA2: c.427T>A] and polyadenylation signal (polyA) [AATAAA>AATGAA (α2), HBA2: c.*92A>G] point mutations. Here, we report two unrelated patients from the Romani population in the Republic of Macedonia, homozygotes for the α2-globin gene variant Hb Agrinio [α29(B10)Leu→Pro; HBA2: c.89T>C]. To date, Hb Agrinio has been described only in individuals of Greek, Cypriot and Spanish origin. Both of our patients had early presentation of the disease (3.5 years and 2 months, respectively) with frequent blood transfusions from early infancy. They have a severe intermediate phenotype of thalassemia (Hb H disease) with hemoglobin (Hb) levels of 7.8 and 7.7 g/dL, respectively. Although the HBA2: c.89T>C mutation results in an α + allele, the severe phenotype of the homozygotes is due to the production of hyperunstable α chains that undergo post translational precipitation. This leads to a greater degree of red cell damage and hemolytic anemia. The detection of Hb Agrinio in two unrelated families of Romani ethnic origin, may suggest it is a founder mutation in this population living in the Republic of Macedonia. Considering the severity of the clinical presentation of the homozygotes or compound heterozygotes for this rare Hb variant, a targeted molecular screening for Hb Agrinio mutation carriers should be considered in all patients of Romani ethnic origin with manifested microcytosis.

  17. HB-EGF expression as a potential biomarker of acquired middle ear cholesteatoma.

    Science.gov (United States)

    Xie, Shumin; Wang, Xiaoli; Ren, Hongmiao; Liu, Xiaoyu; Ren, Jihao; Liu, Wei

    2017-08-01

    The heparin-binding epidermal growth factor-like growth factor (HB-EGF) plays an essential role in the development and invasiveness of cholesteatoma. This study may help to realize the molecular mechanisms underlying the pathogenesis of cholesteatoma and make HB-EGF a promising target for drug intervention of cholesteatoma. To detect HB-EGF expression in human surgical specimens of acquired middle ear cholesteatoma and analyze its functional role as a regulator of epithelial keratinocytes hyperproliferation. A total of 34 patients who underwent surgical treatment for middle ear cholesteatoma were recruited in the study. The mRNA and protein expression of HB-EGF in middle ear cholesteatoma tissues and normal postauricular skin tissues was investigated by real-time quantitative reverse-transcription-polymerase chain reaction (RT-qPCR), immunohistochemical staining, and western blot. The correlation between bone resorption degree and HB-EGF expression was also analyzed. On average, compared with normal postauricular skin, expression of HB-EGF mRNA in the cholesteatoma epithelium was significantly elevated 2.41-fold by RT-qPCR, and HB-EGF protein significantly upregulated 2.32-fold by western blot. Positive HB-EGF immunostaining observed in the basal and suprabasal layers of cholesteatoma epithelium was significantly stronger than in normal postauricular skin. Meanwhile, an obviously positive correlation between HB-EGF protein expression and bone resorption degree was discovered.

  18. Hb Melusine and Hb Athens-Georgia: potentially underreported in the Belgian population? Four cases demonstrating the lack of detection using common CE-HPLC methods either for glycated hemoglobin (HbA1C) analysis or Hb variant screening.

    Science.gov (United States)

    Peeters, Bart; Brandt, Inger; Desmet, Koenraad; Harteveld, Cornelis L; Kieffer, Davy

    2016-12-01

    Suspected hemoglobin (Hb) variants, detected during HbA 1C measurements should be further investigated, determining the extent of the interference with each method. This is the first report of Hb Melusine and Hb Athens-Georgia in Caucasian Belgian patients. Intervention & Technique: Since common CE-HPLC methods for HbA 1C analysis or Hb variant screening are apparently unable to detect these Hb variants, their presence might be underestimated. HbA 1C analysis using CZE, however, alerted for their presence. Moreover, in case of Hb Melusine, even Hb variant screening using CZE was unsuccessful in its detection. Fortunately, carriage of Hb Melusine or Hb Athens-Georgia variants has no clinical implications and, as shown in this report, no apparent difference in HbA 1C should be expected.

  19. A case of iron deficiency anemia with co-existing Hb Fontainebleau.

    Directory of Open Access Journals (Sweden)

    Abhishek HL Purohit

    2014-06-01

    Full Text Available Hb Fontainebleaue is a rare alpha chain variant in the Indian population which generates an unknown peak on hemoglobin HPLC study and does cause diagnostic difficulty to those who are not acquainted with this entity. We present a case of Hb Fontainebleau, an eighteen year old patient who presented with symptoms related to anemia to our department and unknown peak observed in HPLC plots lead us to family study and molecular characterization for this case.

  20. Nuclear translocation of the cytoplasmic domain of HB-EGF induces gastric cancer invasion

    Directory of Open Access Journals (Sweden)

    Shimura Takaya

    2012-05-01

    Full Text Available Abstract Background Membrane-anchored heparin-binding epidermal growth factor-like growth factor (proHB-EGF yields soluble HB-EGF, which is an epidermal growth factor receptor (EGFR ligand, and a carboxy-terminal fragment of HB-EGF (HB-EGF-CTF after ectodomain shedding. We previously reported that HB-EGF-CTF and unshed proHB-EGF which has the cytoplasmic domain of proHB-EGF (HB-EGF-C, translocate from the plasma membrane to the nucleus and regulate cell cycle after shedding stimuli. However, the significance of nuclear exported HB-EGF-C in human gastric cancer is unclear. Methods We investigated the relationship between intracellular localization of HB-EGF-C and clinical outcome in 96 gastric cancer patients treated with gastrectomy. Moreover, we established stable gastric cancer cell lines overexpressing wild-type HB-EGF (wt-HB-EGF and mutated HB-EGF (HB-EGF-mC, which prevented HB-EGF-C nuclear translocation after shedding. Cell motility between these 2 gastric cancer cell lines was investigated using a transwell invasion assay and a wound healing assay. Results Of the 96 gastric cancer cases, HB-EGF-C immunoreactivity was detected in both the nucleus and cytoplasm in 19 cases (19.8 % and in the cytoplasm only in 25 cases (26.0 %. The nuclear immunoreactivity of HB-EGF-C was significantly increased in stage pT3/4 tumors compared with pT1/2 tumors (T1/2 vs. T3/4: 11.1 % vs. 36.4 %, P  Conclusions Both the function of HB-EGF as an EGFR ligand and a novel signal for HB-EGF-C nuclear translocation induce gastric cancer growth, whereas HB-EGF-C nuclear translocation independently plays a critical role in gastric cancer invasion. The present study demonstrated that HB-EGF-C nuclear translocation might be crucial in gastric cancer invasion. HB-EGF-C nuclear translocation may offer a prognostic marker and a new molecular target for gastric cancer therapy.

  1. Nuclear translocation of the cytoplasmic domain of HB-EGF induces gastric cancer invasion.

    Science.gov (United States)

    Shimura, Takaya; Yoshida, Michihiro; Fukuda, Shinji; Ebi, Masahide; Hirata, Yoshikazu; Mizoshita, Tsutomu; Tanida, Satoshi; Kataoka, Hiromi; Kamiya, Takeshi; Higashiyama, Shigeki; Joh, Takashi

    2012-05-30

    might be crucial in gastric cancer invasion. HB-EGF-C nuclear translocation may offer a prognostic marker and a new molecular target for gastric cancer therapy.

  2. BASES MOLECULARES DA ABSORÇÃO DO FERRO

    Directory of Open Access Journals (Sweden)

    A. A. MACHADO

    2009-03-01

    Full Text Available

    O ferro é um elemento essencial a todos os organismos vivos e alterações em sua homeostase resultam em quadro de deficiência ou acúmulo, ambos com alta prevalência e relevância clínica. A última década foi marcada pela geração de conhecimentos importantes, que estão contribuindo para a elucidação dos mecanismos moleculares da homeostase do ferro. Foram identificadas proteínas, envolvidas na absorção intestinal do ferro não-heme, e progressos significativos foram feitos no entendimento da regulação da absorção intestinal do ferro, sendo identificadas várias moléculas candidatas. As bases moleculares da homeostase do ferro ainda não foram totalmente elucidadas, porém as informações já existentes sugerem que, em condições fisiológicas, a absorção, o transporte e o armazenamento sejam feitos por moléculas altamente especializadas e, em especial, a absorção, com mecanismos saturáveis em baixa concentração. No entanto, a absorção pode ocorrer por vias menos sujeitas ao controle, dependendo da sobrecarga e da natureza química do composto utilizado. Estas informações advogam a favor de uma revisão nas estratégias de combate à anemia ferropriva. PALAVRAS-CHAVE: Absorção do ferro; DMT-1; hepahestina; ceruloplasmina; ferroportina; hepcidina.

  3. Nuclear translocation of the cytoplasmic domain of HB-EGF induces gastric cancer invasion

    International Nuclear Information System (INIS)

    Shimura, Takaya; Higashiyama, Shigeki; Joh, Takashi; Yoshida, Michihiro; Fukuda, Shinji; Ebi, Masahide; Hirata, Yoshikazu; Mizoshita, Tsutomu; Tanida, Satoshi; Kataoka, Hiromi; Kamiya, Takeshi

    2012-01-01

    HB-EGF-C nuclear translocation induce gastric cancer growth, whereas HB-EGF-C nuclear translocation independently plays a critical role in gastric cancer invasion. The present study demonstrated that HB-EGF-C nuclear translocation might be crucial in gastric cancer invasion. HB-EGF-C nuclear translocation may offer a prognostic marker and a new molecular target for gastric cancer therapy

  4. Nuclear translocation of the cytoplasmic domain of HB-EGF induces gastric cancer invasion

    Science.gov (United States)

    2012-01-01

    and a novel signal for HB-EGF-C nuclear translocation induce gastric cancer growth, whereas HB-EGF-C nuclear translocation independently plays a critical role in gastric cancer invasion. The present study demonstrated that HB-EGF-C nuclear translocation might be crucial in gastric cancer invasion. HB-EGF-C nuclear translocation may offer a prognostic marker and a new molecular target for gastric cancer therapy. PMID:22646534

  5. Avaliação de Hb A2 e Hb F em doadores de sangue de região malarígena da Amazônia Oriental brasileira por HPLC Evaluation of Hb A2 and Hb F by HPLC in blood donors from the malaria endemic region of Eastern Amazon of Brazil

    Directory of Open Access Journals (Sweden)

    Wanessa C. Souza

    2003-01-01

    Full Text Available In malaria endemic regions of Africa, resistance to infection by Plasmodium has been observed in under 6-month-old children, when there are higher fetal hemoglobin (Hb F levels. Research performed in the São José do Rio Preto region, central-east Brazil, reported increased levels of Hb F in blood donors. The purpose of this work was to evaluate the A2 hemoglobin (Hb A2 and Hb F concentrations in blood donors deriving from the Brazilian malaria endemic region. Forty-five blood donor samples from Macapá, from patients with varying genders, ages and ethnic origins, were collected by venous puncture after informed consent was obtained. The samples were analyzed by High Performance Liquid Chromatography (HPLC - System Variant (Bio-Rad. The HPLC demonstrated sensitivity and rapidity in the identification and measurement of the hemoglobins and gave precise results. Moreover, it provided measurement of hemoglobin variants, even when they were present in small amounts, providing a diagnosis of hemoglobinopathies. Hb F levels above the normal were observed in 33.3% of the analyzed samples. The presence of increased Hb F can suggest resistance to infection by Plasmodium falciparum, as there have been reports that infected red blood cells interfere in the development of the parasite.

  6. Detection of Co-inheritance of Hb Hope and Hb Constant Spring in Three Thai Samples by Capillary Electrophoresis.

    Science.gov (United States)

    Panyasai, Sitthichai; Pornprasert, Sakorn

    2016-06-01

    The diagnosis of co-inheritance of Hb Hope [β136(H14)Gly → Asp, GGT > GAT] and Hb constant spring [Hb CS; α142, Term → Gln (TAA > CAA IN α2)] by high performance liquid chromatography (HPLC) is difficult because Hb Hope has a HPLC elution pattern similar to that of Hb Pyrgos, Hb New York, Hb Kodaira, and Hb Phimai. Moreover, the Hb CS mRNA, as well as the gene product, are unstable and present at a low level in peripheral blood. We report the use of a capillary electrophoresis (CE) for diagnosis of co-inheritance of Hb Hope and Hb CS in 3 Thai females who had mild anemia with Hb and Hct varying from 91-114 g/L to 0.28-0.36 L/L, respectively. Hb Hope eluted with a retention time of 125-140 s (Zone 10) of CE electrophoregram. Furthermore, the peak of Hb CS at the retention time of 245-250 s (Zone 2) was observed in these samples. In addition, the manual analysis by taking the non-black area under both peaks of HbA and Hb Hope (inverted V) into account provided the corrected Hb CS levels which are useful in screening of heterozygote or homozygote for Hb CS. Thus, the CE method provides an accurate diagnosis of Hb Hope and Hb CS which is useful in genetic counseling, prevention and control programs for these hemoglobinopathies.

  7. Measurement of HbA1c and HbA2 by Capillarys 2 Flex Piercing HbA1c programme for simultaneous management of diabetes and screening for thalassemia.

    Science.gov (United States)

    Ke, Peifeng; Liu, Jiawei; Chao, Yan; Wu, Xiaobin; Xiong, Yujuan; Lin, Li; Wan, Zemin; Wu, Xinzhong; Xu, Jianhua; Zhuang, Junhua; Huang, Xianzhang

    2017-10-01

    Thalassemia could interfere with some assays for haemoglobin A 1c (HbA 1c ) measurement, therefore, it is useful to be able to screen for thalassemia while measuring HbA 1c . We used Capillarys 2 Flex Piercing (Capillarys 2FP) HbA 1c programme to simultaneously measure HbA 1c and screen for thalassemia. Samples from 498 normal controls and 175 thalassemia patients were analysed by Capillarys 2FP HbA 1c programme (Sebia, France). For method comparison, HbA 1c was quantified by Premier Hb9210 (Trinity Biotech, Ireland) in 98 thalassaemia patients samples. For verification, HbA 1c from eight thalassaemia patients was confirmed by IFCC reference method. Among 98 thalassaemia samples, Capillarys 2FP did not provide an HbA 1c result in three samples with HbH due to the overlapping of HbBart's with HbA 1c fraction; for the remaining 95 thalassaemia samples, Bland-Altman plot showed 0.00 ± 0.35% absolute bias between two systems, and a significant positive bias above 7% was observed only in two HbH samples. The HbA 1c values obtained by Capillarys 2FP were consistent with the IFCC targets (relative bias below ± 6%) in all of the eight samples tested by both methods. For screening samples with alpha (α-) thalassaemia silent/trait or beta (β-) thalassemia trait, the optimal HbA 2 cut-off values were ≤ 2.2% and > 2.8%, respectively. Our results demonstrated the Capillarys 2FP HbA 1c system could report an accurate HbA 1c value in thalassemia silent/trait, and HbA 2 value (≤ 2.2% for α-thalassaemia silent/trait and > 2.8% for β-thalassemia trait) and abnormal bands (HbH and/or HbBart's for HbH disease, HbF for β-thalassemia) may provide valuable information for screening.

  8. Dietary determinants for Hb-acrylamide and Hb-glycidamide adducts in Danish non-smoking women

    DEFF Research Database (Denmark)

    Outzen, Malene; Egeberg, Rikke; Dragsted, Lars

    2011-01-01

    in erythrocytes were analysed by liquid chromatography/MS/MS. Dietary determinants were evaluated by multiple linear regression analyses adjusted for age and smoking behaviour among ex-smokers. The median for Hb-AA was 35 pmol/g globin (5th percentile 17, 95th percentile 89) and for Hb-GA 21 pmol/g globin (5th......Acrylamide (AA) is a probable human carcinogen that is formed in heat-treated carbohydrate-rich foods. The validity of FFQ to assess AA exposure has been questioned. The aim of the present cross-sectional study was to investigate dietary determinants of Hb-AA and Hb-glycidamide (GA) adducts....... The study included 537 non-smoking women aged 50–65 years who participated in the Diet, Cancer and Health cohort (1993–97). At study baseline, blood samples and information on dietary and lifestyle variables obtained from self-administered questionnaires were collected. From blood samples, Hb-AA and Hb-GA...

  9. A Novel Double Heterozygous Hb D-Punjab/Hb J-Meerut Hemoglobinopathy.

    Science.gov (United States)

    Chandra, Dinesh; Tyagi, Seema; Deka, Roopam; Chauhan, Richa; Seth, Tulika; Saxena, Renu; Pati, H P

    2017-12-01

    A comprehensive laboratory diagnosis of hemoglobinopathies forms an integral part in workup of disorders of globin chain synthesis. Clinical findings, complete blood counts, peripheral smear examination along with hemoglobin (Hb) electrophoresis and/or cation exchange high performance liquid chromatography findings and parental study helps to clinch a final diagnosis. Compound heterozygous hemoglobinopathy presents with variable clinical findings and some of them are picked up on screening tests done as part of routine antenatal workup. Here we report a rare double heterozygous hemoglobinopathy of Hb D-Punjab and Hb J-Meerut in a 35 year antenatal female.

  10. Molecular heterogeneity of Malassezia pachydermatis through RAPD-PCR = Heterogeneidade molecular da Malassezia pachydermatis através de RAPD-PCR

    Directory of Open Access Journals (Sweden)

    Patrícia da Silva Nascente

    2010-04-01

    Full Text Available Several methodologies in molecular biology have been used in theinvestigation of Malassezia pachydermatis and its differentiation into subtypes. Recent molecular research of this species includes the use of samples isolated from canine otitis externa and dermatitis, as well as from healthy animals, having in view an epidemiologicalstudy of the yeast. The aim of this study was to identify molecular differences in M. pachydermatis samples isolated from dogs with otitis externa. The M. pachydermatis strains were analyzed by means of the Random Amplification Primer DNA - Polimerase Chain Reaction (RAPD–PCR for molecular heterogeneity research. DNA extraction was carried out with phenol-chloroform and the RAPD technique using the AGAATCCGCC primer. A variation was observed in the number and arrangement of the bands among the 49 studied isolates, grouped into nine patterns. Isolate groupings were not found to be related to animal breed, age or sex. It was concluded that M. pachydermatis has differences in its molecular profile, as shown by the molecular technique (RAPD – PCR, which allows isolates to be classified into nine subtypes.Várias metodologias em biologia molecular têm sido aplicadas para estudar a M. pachydermatis diferenciando-a em subgrupos. Recentemente utiliza-se a investigação molecular desta espécie isolada de otite externa e dermatite, e também de isolados da mesma de animais hígidos, para um estudo epidemiológico da levedura. O objetivo deste trabalho foi identificar diferenças moleculares entre isolados de M. pachydermatis obtidos de casos de otite externa canina. Para isto, amostras da levedura provenientes de cães com esta enfermidade foram estudadas através da técnica de Polimorfismo de DNA Amplificado aoAcaso - Reação da Polimerase em Cadeia (RAPD–PCR para pesquisa de heterogeneidade molecular. A extração de DNA foi realizada no processo fenol-cloroformio e a técnica de RAPD foi estudada com o primer

  11. Quantitative Trait Loci Influencing Hb F Levels in Southern Thai Hb E (HBB: c.79G>A) Heterozygotes.

    Science.gov (United States)

    Kesornsit, Aumpika; Jeenduang, Nutjaree; Horpet, Dararat; Plyduang, Thunyaluk; Nuinoon, Manit

    2018-01-01

    Variation of fetal hemoglobin (Hb F) expression in heterozygous Hb E (HBB: c.79G>A) individuals is associated with several genetic modifiers and not well understood. This study was undertaken in order to determine the effect of single nucleotide polymorphisms (SNPs), including XmnI G γ (rs7482144), rs766432 on the BCL11A gene and rs9376074 on the HBS1L gene, on Hb F levels in Southern Thai heterozygous Hb E individuals. A total of 97 Southern Thai subjects carrying heterozygous Hb E were selected for the hematological study. After excluding the samples with α-thalassemia (α-thal) interaction or moderate anemia, because both conditions can affect the hematological parameters, the remaining 74 samples were submitted to SNP analysis. Hematological parameters were measured using an automated hematology analyzer and high performance liquid chromatography (HPLC). The results show that rs766432 was strongly associated with increased Hb F levels and rs7482144 was associated with Hb F levels in each subgroup (genotype) of rs766432. This study suggested that the BCL11A locus has a major effect on Hb F levels compared with the XmnI polymorphism in Hb E heterozygotes. This association of Hb F levels with SNPs is useful for the interpretation of hemoglobin (Hb) typing in heterozygous Hb E samples with high Hb F levels. Future research will need to address the better understanding of the mechanisms of the SNPs that regulate Hb F production without stress erythropoiesis in Hb E heterozygotes.

  12. Hemoglobin Constant Spring (Hb CS) Missed by HPLC in an Hb E Trait Pregnancy Resulting in Hb H-CS Disease in a Thai Girl: Utility of Capillary Electrophoresis.

    Science.gov (United States)

    Pornprasert, Sakorn; Saoboontan, Supansa; Wiengkum, Thanatcha

    2016-06-01

    Hemoglobin Constant Spring [Hb CS; α142, Term→Gln (TAA>CAA IN α2)] is often missed by routine laboratory testing, especially in subjects with co-inheritance of β-thalassemia or β-variants. We reported the case of a 1-year-old female with Hb H-CS disease who was born from a father with heterozygous of α-thalassemia-1 Southeast Asian type deletion and a mother with the combination of Hb CS and Hb E [β26 (B8) Glu→Lys, GAG>AAG] trait. A very tiny peak of Hb CS of the mother was easily ignored on the high performance liquid chromatography chromatogram while it was clearly seen on the capillary electrophoresis (CE) electrophoregram. Therefore, the CE is useful in screening for heterozygous Hb CS in a person with Hb E trait. This is of potential benefit for prevention of new cases of Hb H-CS disease.

  13. The super sickling haemoglobin HbS-Oman: a study of red cell sickling, K+ permeability and associations with disease severity in patients heterozygous for HbA and HbS-Oman (HbA/S-Oman genotype).

    Science.gov (United States)

    Al Balushi, Halima W M; Wali, Yasser; Al Awadi, Maha; Al-Subhi, Taimoora; Rees, David C; Brewin, John N; Hannemann, Anke; Gibson, John S

    2017-10-01

    Studying different sickle cell genotypes may throw light on the pathogenesis of sickle cell disease (SCD). Here, the clinical profile, red cell sickling and K + permeability in 29 SCD patients (15 patients with severe disease and 14 with a milder form) of HbA/S-Oman genotype were analysed. The super sickling nature of this Hb variant was confirmed. The red cell membrane permeability to K + was markedly abnormal with elevated activities of P sickle , Gardos channel and KCl cotransporter (KCC). Results were consistent with Ca 2+ entry and Mg 2+ loss via P sickle stimulating Gardos channel and KCC activities. The abnormal red cell behaviour was similar to that in the commonest genotype of SCD, HbSS, in which the level of mutated Hb is considerably higher. Although activities of all three K + transporters also correlated with the level of HbS-Oman, there was no association between transport phenotype and disease severity. The super sickling behaviour of HbS-Oman may obviate the need for solute loss and red cell dehydration to encourage Hb polymerisation, required in other SCD genotypes. Disease severity was reduced by concurrent α thalassaemia, as observed in other SCD genotypes, and represents an obvious genetic marker for prognostic tests of severity in young SCD patients of the HbA/S-Oman genotype. © 2017 John Wiley & Sons Ltd.

  14. Incidence of hemoglobinopathies and thalassemias in Northern Alberta. Establishment of reference intervals for HbF and HbA2.

    Science.gov (United States)

    Rodriguez-Capote, Karina; Higgins, Trefor N

    2015-07-01

    The aims of this study were to identify the incidence of hemoglobinopathies and thalassemias in Northern Alberta and calculate the reference intervals (RI) for hemoglobin (Hb) HbF and HbA2. A retrospective ad-hoc analysis of the structural Hb variants and thalassemias identified on patients who had a hemoglobinopathy/thalassemia investigation performed between February 1 to December 31, 2013. Results were extracted from the Laboratory Information System. Statistical analysis was performed using MedCalc® version 11.4.2.0 for Windows software. 6616 hemoglobinopathy/thalassemia investigations and HbS screens were physician requested and 602 Hb variants were fortuitously found during HbA1c analysis. 3438 were interpreted as "normal" and 532 were classified as iron deficient. 3306 individuals, with age ranging from 3 to 92 years were included in the RI calculation. HbA2 RI was 2.3% to 3.4% and HbF 0.0% to 1.8%. 524 and 423 α and β thalassemia traits respectively were identified. Additionally ten δβ thalassemia traits and twelve cases of HbH disease were identified. Regarding hemoglobinopathies, 7% were classified as α-chain variants and 93% as β-chain variants with HbS (46%), HbE (16%), HbD Punjab (8%) and HbC (7%) traits being the most prevalent. We also documented 20 homozygous hemoglobinopathies and 36 compound/double heterozygous hemoglobinopathies. A wide diversity of hemoglobinopathies is found in the Northern Alberta population, 80% of the hemoglobinopathies were found as a reflex to HbA1c testing. Reference intervals for HbF and HbA2 were established. Copyright © 2015 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  15. Detection of compound heterozygous of hb constant spring and hb q-Thailand by capillary electrophoresis and high performance liquid chromatography.

    Science.gov (United States)

    Pornprasert, Sakorn; Punyamung, Manoo

    2015-06-01

    A capillary electrophoresis (CE) has proven to be superior to a high performance liquid chromatography (HPLC) in the detection of hemoglobin Constant Spring (Hb CS). Thus the aim of this study was to analyze the efficacy of CE and HPLC for the detection of Hb CS in samples with compound heterozygous of Hb CS and Hb Q-Thailand. Hemoglobin analysis was performed in blood samples of 2 patients with compound heterozygous of Hb CS and Hb Q-Thailand by using HPLC and CE. The HPLC chromatogram and CE electrophoregram of the two techniques were compared. Hb CS was not found on HPLC chromatogram while Hb QA2 (α2 (QT)δ2), a derivative of Hb Q-Thailand, was presented at the retention time of 4.70-4.80 min and it was close to the retention time of Hb CS. On CE electrophoregram, Hb CS was presented at zone 2 (Z2) and it was distinctly separated from Hb QA2 which was presented at Z1. Therefore, CE was more efficient to the HPLC for diagnosis of compound heterozygous of Hb CS and Hb Q-Thailand.

  16. Comparação de metodologia utilizada para a detecção de Hemoglobina S (Hb S em doadores de sangue

    Directory of Open Access Journals (Sweden)

    Prudêncio Brígida C. A. B.

    2000-01-01

    Full Text Available O Brasil apresenta alta prevalência de hemoglobina S, com nítidas diferenças regionais marcadas pelos processos de miscigenação da população. A presença desta hemoglobina tem sido objeto de estudo, não só em pacientes com anemia falciforme (homozigotos para hemoglobina S - Hb SS, mas também em portadores desta variante de hemoglobina em heterozigose (Hb AS. As complicações clínicas dos portadores são influenciadas por fatores genéticos e ambientais. De acordo com a portaria 1376 de 19 de novembro de 1993 para Normas técnicas de coleta, processamento e transfusão de sangue, componentes e derivados, do Ministério da Saúde, deve ser realizada a detecção de hemoglobinas anormais em doadores de sangue. Diante desta normatização e às taxas de hemoglobina S em nossa população, objetivamos no presente trabalho a identificação da hemoglobina S, utilizando técnicas de triagem utilizadas na rotina de Bancos de Sangue, como o kit de identificação para hemoglobina S da Diamed, comercializado pela designação ID-Hb S, e o teste de solubilidade. Os casos que apresentaram positividade nesta triagem foram posteriormente confirmados em eletroforese em pH alcalino e ácido. Do total de 5.416 doadores de sangue analisados pelo teste de triagem (ID - Hb S Diamed e solubilidade, 50 (0,92% apresentaram hemoglobina S. Após confirmação eletroforética evidenciamos a compatibilidade das técnicas em 100 % dos casos analisados. O teste da Diamed apresenta custo de R$ 1,20 por doador e o de solubilidade R$ 0,14. Pelos resultados obtidos sugerimos o uso do teste de solubilidade como de escolha, para triagem de hemoglobina S em bancos de sangue, não só pela eficácia e praticidade, como também pelo baixo custo.

  17. Complex structure of the supernova remnant HB 3

    Science.gov (United States)

    Leahy, D. A.; Venkatesan, D.; Long, K. S.; Naranan, S.

    1985-01-01

    HB 3 is an old, large (84 pc diameter) supernova remnant associated with the W3 H II region/molecular cloud complex. Observations of the imaging proportional counter (IPC) onboard the Einstein X-ray astronomy satellite have been reprocessed to yield a contour map of X-ray brightness and spectra of various regions of this remnant. The measured IPC flux is 2.4 x 10 to the -11th ergs per sq cm per s, giving a 0.2-4 keV luminosity of 1.6 x 10 to the 35th ergs/s for a column densityof 6 x 10 to the 21st per sq cm. The measured X-ray temperatures reveal a decrease from center to limb of the remnant of 1-0.3 keV. HB 3 is in the late adiabatic blast-wave phase of evolution, 30,000 to 50,000 yr old and with an initial blast energy of 3 x 10 to the 50th ergs. The X-ray map is compared with available radio and optical images. In X-rays, HB 3 has two components - a diffuse emission inside the 84 pc radio remnant and a ring of emission at the center of 30 pc in diameter. The diffuse emission is similar to that from other supernova remnants which are moderately obscured (column density, nH approximately 10 to the 22nd per sq cm). Three possibilities for the origin of the ring are explored: (1) a second supernova remnant, (2) a shocked shell in the interstellar medium surrounding HB 3, and (3) reverse-shock heated ejecta. There is no hot neutron star within the remnant.

  18. Hematological Characterizations and Molecular Diagnostic Aspects of Hb Wiangpapao [α44(CE2)Pro→Ser (α1), CCG>TCG; HBA1: c.133C>T], a New α-Globin Variant Found in a Pregnant Thai Woman.

    Science.gov (United States)

    Panyasai, Sitthichai; Pornprasert, Sakorn

    2017-03-01

    We report the hematological parameters and provide a rapid molecular analysis method for detection of Hb Wiangpapao [α44(CE2)Pro→Ser, CCG>TCG; HBA1: c.133C>T], a new α-globin variant found in a pregnant Thai woman. Her red cell indices were measured by an automated blood counter. The results were: red blood cell (RBC) count 4.03 × 10 12 /L, Hb 13.1 (g/dL), packed cell volume (PCV) 0.39 L/L, mean corpuscular volume (MCV) 97.0 fL, mean corpuscular hemoglobin (Hb) (MCH) 32.5 pg, mean corpuscular Hb concentration (MCHC) 33.4 g/dL, and RBC distribution width (RDW) 9.4%. The Hb typing by high performance liquid chromatography (HPLC) showed 13.6% abnormal Hb at a retention time of 2.20 min. that was difficult to distinguish from Hb A. On the capillary electrophoresis (CE) electropherogram, this hemoglobinopathy peak did not separate from the Hb A peak. DNA sequencing showed a C>T transition at the first position of codon 44 (CCG>TCG) of the α1-globin gene that led to a substitution of proline for serine. This mutation has not been recorded in the public databases. Therefore, we named it Hb Wiangpapao as it was first discovered in the Wiangpapao District, Chiang Rai, Thailand. The multiplex allele-specific polymerase chain reaction (ASPCR) for detection of Hb Wiangpapao was developed and revealed a 510 bp specifically amplified fragment. The better understanding of hematological characterizations and the newly developed multiplex ASPCR for diagnosis of Hb Wiangpapao are useful for genetic counseling and family education.

  19. Triagem de hemoglobinopatias e avaliação da degeneração oxidativa da hemoglobina em trabalhadores portadores do traço falciforme (HbAS, expostos a riscos ocupacionais Screening of abnormal hemoglobin and the evaluation of oxidative degeneration of hemoglobin among workers with the sickle cell trait (HbAS, exposed to occupational hazards

    Directory of Open Access Journals (Sweden)

    Isaac L. Silva Filho

    2005-09-01

    Full Text Available Desde os anos 40, quando foram realizados os primeiros trabalhos de triagem para hemoglobinas anormais na população brasileira, tem sido descrita uma elevada prevalência destas em nosso meio, especialmente a hemoglobina S que, a despeito da heterogeneidade de sua distribuição geográfica, quase sempre é a mais freqüente nas diversas regiões estudadas. Aliado a este fato, estudos recentes têm demonstrado uma maior susceptibilidade desta a oxidação, tornando-a mais sensível ao estresse oxidativo que a hemoglobina normal (HbAA, mesmo em se tratando de portadores heterozigotos (HbAS. Tendo em vista que algumas substâncias químicas são comprovadamente meta-hemoglobinizantes, que alguns fatores ambientais podem influenciar na morbidade da anemia falciforme e também o pouco e controverso conhecimento de que se dispõe a respeito de portadores do traço falciforme, este estudo, além da pesquisa de hemo-globinas anormais, avaliou também a degeneração oxidativa da hemoglobina, através da pesquisa de corpos de Heinz e dosagem de meta-hemoglobina em uma população de trabalhadores portadores do traço falciforme, expostos a riscos ocupacionais. Foram triadas 2.190 amostras sangüíneas entre Outubro de 1999 e Dezembro de 2001. A população estudada foi constituída de trabalhadores de ambos os sexos com idades variando entre 18 e 76 anos. Os resultados evidenciaram 4,7% portadores de hemoglobinas anormais na população analisada, sendo que a hemoglobina S foi a mais freqüente - 3,2% (71. Trabalhadores portadores do traço falciforme apresentaram uma chance 14 vezes maior de possuírem valores aumentados de meta-hemoglobina em relação aos trabalhadores com genótipo AA, porém, esta diferença não foi estatisticamente significativa.Hemoglobinopathies are frequent hereditary diseases in Brazilian population and have been a public health problem. This study reports the screening of abnormal hemoglobin among Fiocruz`s employees, as

  20. Interaction between Hb E and Hb Yala (HBB:c.129delT); a novel frameshift beta globin gene mutation, resulting in Hemoglobin E/β0 thalassemia.

    Science.gov (United States)

    Ekwattanakit, Supachai; Riolueang, Suchada; Viprakasit, Vip

    2018-03-01

    There are more than 200 known mutations found in patients with β-thalassemia, a possibility to identify an unknown or novel mutation becomes less possible. Here, we report a novel mutation in a patient from Thailand who presented with chronic hemolytic anemia. A comprehensive hematology and DNA analysis was applied in the index patient and her mother. Hematological and hemoglobin analyses were consistent with the clinical diagnosis of Hb E/β 0 -thalassemia. However, we could find only Hb E heterozygous mutation using our common polymerase chain reaction-based mutation detection of the β-globin genes. Furthermore, the molecular analysis demonstrated a novel T-deletion at codon 42 of the second exon of the β-globin gene which we named 'Hb Yala' according to the origin of this index family. This mutation was assumed to generate a truncated β-globin chain terminating at codon 60 with possible unstable variant leading to a 'null' or β 0 -thalassemia. However, the clinical phenotype was surprisingly mild and no other ameliorating genetic factors, including co-inheritance of α-thalassemia and high propensity of Hb F by Xmn I polymorphism, were found. This report has provided evidence that genotype-phenotype correlation in thalassemia syndromes is highly complex and a correct clinical severity classification of thalassemia should be mainly based on clinical evaluation.

  1. Avaliação de condições de cultivo para aumento da produção de P(3HB) por Bacillus megaterium e modelagem do bioprocesso

    OpenAIRE

    Debora Jung Luvizetto Faccin

    2012-01-01

    O poli(3-hidroxibutirato) é um biopolímero obtido a partir de fontes renováveis e é um poliéster biodegradável. Possui um grande potencial de aplicação principalmente em artefatos e embalagens descartáveis e também na área médica, devido sua biocompatibilidade. Neste trabalho foi estudada a produção de P(3HB) por Bacillus megaterium em meio mineral, buscando o aumento na produção deste biopolímero, bem como representar matematicamente este bioprocesso. Foram avaliadas a influência do pH e da ...

  2. Relationship between Hb and HbA1c in Japanese adults: an analysis of the 2009 Japan Society of Ningen Dock database.

    Science.gov (United States)

    Takahashi, Eiko; Moriyama, Kengo; Yamakado, Minoru

    2014-06-01

    We investigated the effect of Hb on HbA1c levels in 265,427 Japanese individuals. The divergence between fasting plasma glucose (FPG) and HbA1c levels increased with lower Hb, resulting in HbA1c levels that were higher in relation to than the FPG levels. Similarly, the correlation between FPG and HbA1c levels, stratified by Hb, weakened as Hb decreased. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  3. First Case of a Compound Heterozygosity for Two Nondeletional α-Thalassemia mutations, Hb Constant Spring and Hb Quong Sze.

    Science.gov (United States)

    Zhou, Jian-Ying; Yan, Jin-Mei; Li, Jian; Li, Dong-Zhi

    2016-06-01

    Nondeletional α-thalassemia (α-thal) is the result of point mutations in critical regions of the α-globin genes, affecting mRNA processing, mRNA translation, or α-globin stability. Hb Constant Spring (Hb CS, HBA2: c.427T > C) is the most common nondeletional α-thal that results from a nucleotide substitution at the termination codon of the α2-globin gene. Hb Quong Sze (Hb QS, HBA2: c.377T > C) is another nondeletional α-thal in South China with the missense mutation at codon 125 of the α2-globin gene making this hemoglobin (Hb) variant highly unstable. Although homozygosity for Hb CS (α(CS)α/α(CS)α) or Hb QS (α(QS)α/α(QS)α) has been reported, clinical pictures vary from severe hemolysis that developed early in life to only mild anemia, no clinical phenotypic data of compound heterozygosity for Hb CS/Hb QS (α(CS)α/α(QS)α) has been described. In this report we describe an adult case with such a compound heterozygosity who presented with a mild α-thal.

  4. Comparative haematological parameters of HbAA and HbAS genotype children infected with Plasmodium falciparum malaria in Yemen.

    Science.gov (United States)

    Albiti, Anisa H; Nsiah, Kwabena

    2014-04-01

    Sickle haemoglobin (HbS) is known to offer considerable protection against falciparum malaria. However, the mechanism of protection is not yet completely understood. In this study, we investigate how the presence of the sickle cell trait affects the haematological profile of AS persons with malaria, in comparison with similarly infected persons with HbAA. This study is based on the hypothesis that the sickle cell trait plays a protective role against malaria. Children from an endemic malaria transmission area in Yemen were enrolled in this study. Hematological parameters were estimated using manual methods, the percentage of parasite density on stained thin smear was calculated, haemoglobin genotypes were determined on paper electrophoresis, ferritin was measured using enzyme-linked immunosorbent assay, serum iron and TIBC were assayed using spectrophotometer, transferrin saturation index was calculated by dividing serum iron by TIBC and expressing the result as a percentage. Haematological parameters were compared in HbAA- and HbAS-infected children. Falciparum malaria parasitaemia was confirmed in the blood smears of 62 children, 44 (55.7%) of AA and 18 (37.5%) AS, so there was higher prevalence in HbAA children (P = 0.047). Parasite density was lower in HbAS- than HbAA-infected children (P = 0.003). Anaemia was prominent in malaria-infected children, with high proportions of moderate and severe forms in HbAA (P = 0.001). The mean levels of haemoglobin, packed cell volume, reticulocyte count, platelets count, lymphocytes, eosinophils, and serum iron were significantly lower while total leukocytes, immature granulocytes, monocytes, erythrocyte sedimentation rate, transferrin saturation, and serum ferritin were significantly higher in HbAA-infected children than HbAS-infected children. Infection with Plasmodium falciparum malaria caused more significant haematological alterations of HbAA children than HbAS. This study supports the observation that sickle cell trait

  5. Genotipos da haptoglobina nas doenças falciformes

    OpenAIRE

    Magnun Nueldo Nunes dos Santos

    2009-01-01

    Resumo: O estresse oxidativo, particularmente no endotélio, exerce forte influência na gênese da vaso-oclusão e, assim, na evolução clínica e sobrevida de pacientes com Doenças Falciformes (DF). A fisiopatologia das DF está centralizada na propriedade de polimerização da desoxi-hemoglobina (Hb) S, mas fatores genéticos têm atuado como moduladores de suas complicações clínicas. A haptoglobina (Hp) é uma glicoproteína plasmática cuja função primordial é se ligar à Hb livre no plasma, impedindo...

  6. Hydroxyurea decreases hospitalizations in pediatric patients with Hb SC and Hb SB+ thalassemia

    Directory of Open Access Journals (Sweden)

    Lebensburger JD

    2015-12-01

    Full Text Available Jeffrey D Lebensburger, Rakeshkumar J Patel, Prasannalaxmi Palabindela, Christina J Bemrich-Stolz, Thomas H Howard, Lee M HilliardDivision of Pediatric Hematology Oncology, University of Alabama at Birmingham, Birmingham, AL, USAPurpose: Patients with hemoglobin SC (Hb SC and hemoglobin SB+ (Hb SB+ thalassemia suffer from frequent hospitalizations yet strong evidence of a clinical benefit of hydroxyurea (HU in this population is lacking. Patients with recurrent hospitalizations for pain crisis are offered HU at our institution based on small cohort data and anecdotal benefit. This study identifies outcomes from a large cohort of patients with Hb SC and SB+ thalassemia who were treated with HU for 2 years.Materials and methods: A retrospective review was conducted of 32 patients with Hb SC and SB+ thalassemia who were treated with HU. We reviewed the number, and reasons for hospitalization in the 2 years prior to, and 2 years post-HU treatment as well as laboratory changes from baseline, over 1 year.Results: Patients with Hb SC and SB+ thalassemia started on HU for frequent pain, had a significant reduction in hospitalizations over 2 years as compared to the 2 years prior to HU initiation (mean total hospitalizations/year: pre-HU: 1.6 vs post-HU 0.4 hospitalizations, P<0.001; mean pain hospitalizations/year: pre-HU 1.5 vs post-HU 0.3 hospitalizations, P<0.001. Patients demonstrated hematologic changes including an increase in percent fetal hemoglobin (%HbF pre–post HU (4.5% to 7.7%, P=0.002, mean corpuscular volume (74 to 86 fL, P<0,0001, and decrease in absolute neutrophil count (5.0 to 3.2×109/L, P=0.007. Patients with higher doses of HU demonstrated the greatest reduction in hospitalizations but this was unrelated to absolute neutrophil count.Conclusion: This cohort of patients with Hb SC and SB+ thalassemia provides additional support for using HU in patients with recurrent hospitalizations for pain. A large randomized multicenter trial of

  7. Seed-specific elevation of non-symbiotic hemoglobin AtHb1: beneficial effects and underlying molecular networks in Arabidopsis thaliana

    Directory of Open Access Journals (Sweden)

    Tschiersch Henning

    2011-03-01

    Full Text Available Abstract Background Seed metabolism is dynamically adjusted to oxygen availability. Processes underlying this auto-regulatory mechanism control the metabolic efficiency under changing environmental conditions/stress and thus, are of relevance for biotechnology. Non-symbiotic hemoglobins have been shown to be involved in scavenging of nitric oxide (NO molecules, which play a key role in oxygen sensing/balancing in plants and animals. Steady state levels of NO are suggested to act as an integrator of energy and carbon metabolism and subsequently, influence energy-demanding growth processes in plants. Results We aimed to manipulate oxygen stress perception in Arabidopsis seeds by overexpression of the non-symbiotic hemoglobin AtHb1 under the control of the seed-specific LeB4 promoter. Seeds of transgenic AtHb1 plants did not accumulate NO under transient hypoxic stress treatment, showed higher respiratory activity and energy status compared to the wild type. Global transcript profiling of seeds/siliques from wild type and transgenic plants under transient hypoxic and standard conditions using Affymetrix ATH1 chips revealed a rearrangement of transcriptional networks by AtHb1 overexpression under non-stress conditions, which included the induction of transcripts related to ABA synthesis and signaling, receptor-like kinase- and MAP kinase-mediated signaling pathways, WRKY transcription factors and ROS metabolism. Overexpression of AtHb1 shifted seed metabolism to an energy-saving mode with the most prominent alterations occurring in cell wall metabolism. In combination with metabolite and physiological measurements, these data demonstrate that AtHb1 overexpression improves oxidative stress tolerance compared to the wild type where a strong transcriptional and metabolic reconfiguration was observed in the hypoxic response. Conclusions AtHb1 overexpression mediates a pre-adaptation to hypoxic stress. Under transient stress conditions transgenic seeds

  8. Revisiting shape selectivity in liquid chromatography for polycyclic aromatic hydrocarbons (PAHs) - six-ring and seven-ring Cata-condensed PAH isomers of molecular mass 328 Da and 378 Da.

    Science.gov (United States)

    Oña-Ruales, Jorge O; Sander, Lane C; Wilson, Walter B; Wise, Stephen A

    2018-01-01

    The relationship of reversed-phase liquid chromatography (RPLC) retention on a polymeric C 18 stationary phase and the shape of polycyclic aromatic hydrocarbons (PAHs) was investigated for three-ring to seven-ring cata-condensed isomers. We report the first RPLC separation for six-ring and seven-ring cata-condensed PAH isomers. Correlations of LC retention and shape parameters (length-to-breath ratio, L/B and thickness, T) were investigated for 2 three-ring isomers (molecular mass 178 Da), 5 four-ring isomers (molecular mass 228 Da), 11 five-ring isomers (molecular mass 278 Da), 17 six-ring isomers (molecular mass 328 Da), and 20 seven-ring isomers (molecular mass 378 Da). Significant linear correlations were found for all isomer groups (r = 0.71 to 0.94). Nonplanarity of the PAH isomers was found to influence retention (i.e., nonplanar isomers eluting earlier than expected based on L/B) and linear correlations of retention vs. T for isomer groups containing nonplanar isomers were significant (r = 0.71 to 0.86). Graphical abstract.

  9. Hydrops Fetalis Associated with Compound Heterozygosity for Hb Zurich-Albisrieden (HBA2: C.178G > C) and the Southeast Asian (- -SEA/) Deletion.

    Science.gov (United States)

    Yang, Xin; Yan, Jin-Mei; Li, Jian; Xie, Xing-Mei; Zhou, Jian-Ying; Li, Yan; Li, Dong-Zhi

    2016-09-01

    Hb Zurich-Albisrieden [HBA2: c.178G > C; α59(E8)Gly→Arg (α2)] is a rare nondeletional α-thalassemia (α-thal) that results from a nucleotide substitution at codon 59 of the α2-globin gene. In this report, we present a fetus with cardiomegaly, enlarged placenta and increased middle cerebral artery-peak systolic velocity (MCA-PSV) at 25 weeks' gestation. Fetal blood sampling revealed the severe anemia [hemoglobin (Hb) level being 5.5 g/dL] and Hb H (β4) disease-like hematological findings with Hb Bart's (γ4) level of 30.7%. Molecular analysis of the family found that the father was an Hb Zurich-Albisrieden carrier, the mother heterozygous for the - - SEA α 0 -thal deletion, and the fetus was a compound heterozygote for Hb Zurich-Albisrieden and the - - SEA α 0 -thal deletion. Therefore, this was a rare case of Hb Bart's hydrops fetalis associated with Hb Zurich Albisrieden.

  10. HbE/β-Thalassemia and Oxidative Stress: The Key to Pathophysiological Mechanisms and Novel Therapeutics

    Science.gov (United States)

    Sibmooh, Nathawut; Fucharoen, Suthat

    2017-01-01

    Abstract Significance: Oxidative stress and generation of free radicals are fundamental in initiating pathophysiological mechanisms leading to an inflammatory cascade resulting in high rates of morbidity and death from many inherited point mutation-derived hemoglobinopathies. Hemoglobin (Hb)E is the most common point mutation worldwide. The βE-globin gene is found in greatest frequency in Southeast Asia, including Thailand, Malaysia, Indonesia, Vietnam, Cambodia, and Laos. With the wave of worldwide migration, it is entering the gene pool of diverse populations with greater consequences than expected. Critical Issues: While HbE by itself presents as a mild anemia and a single gene for β-thalassemia is not serious, it remains unexplained why HbE/β-thalassemia (HbE/β-thal) is a grave disease with high morbidity and mortality. Patients often exhibit defective physical development, severe chronic anemia, and often die of cardiovascular disease and severe infections. Recent Advances: This article presents an overview of HbE/β-thal disease with an emphasis on new findings pointing to pathophysiological mechanisms derived from and initiated by the dysfunctional property of HbE as a reduced nitrite reductase concomitant with excess α-chains exacerbating unstable HbE, leading to a combination of nitric oxide imbalance, oxidative stress, and proinflammatory events. Future Directions: Additionally, we present new therapeutic strategies that are based on the emerging molecular-level understanding of the pathophysiology of this and other hemoglobinopathies. These strategies are designed to short-circuit the inflammatory cascade leading to devastating chronic morbidity and fatal consequences. Antioxid. Redox Signal. 26, 794–813. PMID:27650096

  11. HbE/β-Thalassemia and Oxidative Stress: The Key to Pathophysiological Mechanisms and Novel Therapeutics.

    Science.gov (United States)

    Hirsch, Rhoda Elison; Sibmooh, Nathawut; Fucharoen, Suthat; Friedman, Joel M

    2017-05-10

    Oxidative stress and generation of free radicals are fundamental in initiating pathophysiological mechanisms leading to an inflammatory cascade resulting in high rates of morbidity and death from many inherited point mutation-derived hemoglobinopathies. Hemoglobin (Hb)E is the most common point mutation worldwide. The β E -globin gene is found in greatest frequency in Southeast Asia, including Thailand, Malaysia, Indonesia, Vietnam, Cambodia, and Laos. With the wave of worldwide migration, it is entering the gene pool of diverse populations with greater consequences than expected. While HbE by itself presents as a mild anemia and a single gene for β-thalassemia is not serious, it remains unexplained why HbE/β-thalassemia (HbE/β-thal) is a grave disease with high morbidity and mortality. Patients often exhibit defective physical development, severe chronic anemia, and often die of cardiovascular disease and severe infections. Recent Advances: This article presents an overview of HbE/β-thal disease with an emphasis on new findings pointing to pathophysiological mechanisms derived from and initiated by the dysfunctional property of HbE as a reduced nitrite reductase concomitant with excess α-chains exacerbating unstable HbE, leading to a combination of nitric oxide imbalance, oxidative stress, and proinflammatory events. Additionally, we present new therapeutic strategies that are based on the emerging molecular-level understanding of the pathophysiology of this and other hemoglobinopathies. These strategies are designed to short-circuit the inflammatory cascade leading to devastating chronic morbidity and fatal consequences. Antioxid. Redox Signal. 26, 794-813.

  12. First Report of a Chinese Family Carrying a Double Heterozygosity for Hb Q-Thailand and Hb J-Bangkok.

    Science.gov (United States)

    Jiang, Fan; Zhou, Jian-Ying; Yan, Jin-Mei; Lu, Yue-Cheng; Li, Dong-Zhi

    2016-11-01

    The double heterozygosity for α and β chain variants leads to the formation of abnormal heterodimer hybrids, which could render laboratory diagnostics in a routine setting difficult. The following is the first report of a double heterozygosity for Hb Q-Thailand [α74(EF3)Asp→His; HBA1: c.223G>C] with α + -thalassemia (α + -thal) and Hb J-Bangkok [β56(D7)Gly→Asp; HBB: c.170G>A] found in a Chinese family. Both subjects were healthy with normal or borderline hematological parameters. Hemoglobin (Hb) analyses showed a novel variant, Hb Q-Thailand and Hb J-Bangkok. Family studies helped in the initial recognition and in making presumptive diagnoses, but definitive diagnoses of these cases with complex α and β chain variants could only be obtained after DNA analysis.

  13. Avaliação da composição molecular da cápsula anterior da lente de cães idosos com catarata de alto risco

    Directory of Open Access Journals (Sweden)

    Ana Paula Hvenegaard

    Full Text Available Resumo: Atualmente, a cápsula anterior e o epitélio da lente tem sido cada vez mais estudados, com o intuito de reduzir as possíveis complicações do pós-operatório da remoção da catarata, tal como a opacidade da cápsula posterior, alteração ocasionada principalmente pela diferenciação e migração das células do epitélio lenticular para a cápsula posterior da lente. O objetivo deste estudo foi analisar a composição molecular da cápsula anterior da lente pela técnica histoquímica de PAS (avaliação de proteoglicanos e picrosirius red (avaliação de colágeno IV, em cães idosos com catarata diabética e não diabética do tipo hipermadura, submetidos ao uso ou não de azul de tripano a 0,1 % durante a facoemulsificação. Vinte e sete cães foram estudados, incluindo 21 fêmeas e 6 machos, de 8 a 12 anos de idade (média = 9,6 anos, de diversas raças e divididos em 2 grupos: GC (catarata hipermadura e GCD (catarata diabética. Os resultados das análises realizadas mostraram que ambas as amostras, tanto as provenientes das cataratas hipermaduras, quanto das diabéticas, apresentam semelhante composição molecular de proteoglicanos e colágeno IV e isto independente da utilização de azul de tripano a 0,1 %. Conclui-se, portanto, que se os resultados obtidos forem decorrentes de alterações provocadas pelo rápido metabolismo da catarata diabética e pela cronicidade da catarata hipermadura sugere-se que o comprometimento da estrutura capsular seja de intensidade equivalente e, por consequência, que isto também possa prejudicar o metabolismo das células do epitélio anterior da lente, diminuindo assim a incidência da opacidade da cápsula posterior de cães com catarata diabética e hipermadura submetidos à facoemulsificação.

  14. Stress analysis of the HFIR HB-2 and HB-3 beam tube nozzles

    International Nuclear Information System (INIS)

    Williams, P.T.

    1998-08-01

    The results of three-dimensional linear elastic stress analyses of the HFIR HB-2 and HB-3 nozzles are presented in this report. Finite element models were developed using the PATRAN pre-processing code and translated into ABAQUS input file format. A scoping analysis using simple geometries with internal pressure loading was carried out to assess the capabilities of the ABAQUS/Standard code to calculate maximum principal stress distributions within cylinders with and without holes. These scoping calculations were also used to provide estimates for the variation in tangential stress around the rim of a nozzle using the superposition of published closed-form solutions for the stress around a hole in an infinite flat plate under uniaxial tension. From the results of the detailed finite element models, peak stress concentration factors (based on the maximum principal stresses in tension) were calculated to be 3.0 for the HB-2 nozzle and 2.8 for the HB-3 nozzle. Submodels for each nozzle were built to calculate the maximum principal stress distribution in the weldment region around the nozzle, where displacement boundary conditions for the submodels were automatically calculated by ABAQUS using the results of the global nozzle models. Maximum principal stresses are plotted and tabulated for eight positions around each nozzle and nozzle weldment

  15. Characterization of a Novel Anti-Human HB-EGF Monoclonal Antibody Applicable for Paraffin-Embedded Tissues and Diagnosis of HB-EGF-Related Cancers.

    Science.gov (United States)

    Iwamoto, Ryo; Takagi, Mika; Akatsuka, Jun-Ichi; Ono, Ken-Ichiro; Kishi, Yoshiro; Mekada, Eisuke

    2016-04-01

    Heparin-binding EGF-like growth factor (HB-EGF) is a member of the EGF family of growth factors that bind to and activate the EGF receptor (EGFR/ErbB1) and ErbB4. HB-EGF plays pivotal roles in pathophysiological processes, including cancer. Thus, monoclonal antibodies (mAbs) for HB-EGF detection could be an important tool in the therapeutic diagnosis of HB-EGF-related cancers and other diseases. However, few mAbs, especially those applicable for immunohistochemistry (IHC), have been established to date. In this study, we generated a clone of hybridoma-derived mAb 2-108 by immunizing mice with recombinant human HB-EGF protein expressed by human cells. The mAb 2-108 specifically bound to human HB-EGF but not to mouse HB-EGF and was successful in immunoblotting, even under reducing conditions, immunoprecipitation, and immunofluorescence for unfixed as well as paraformaldehyde-fixed cells. Notably, this mAb was effective in IHC of paraffin-embedded tumor specimens. Epitope mapping analysis showed that mAb 2-108 recognized the N-terminal prodomain in HB-EGF. These results indicate that this new anti-HB-EGF mAb 2-108 would be useful in the diagnosis of HB-EGF-related cancers and would be a strong tool in both basic and clinical research on HB-EGF.

  16. Hb A1c Determination by Capillary Electrophoresis is an Efficient Method for Detecting β-Thalassemias and Hemoglobin Variants.

    Science.gov (United States)

    Orts, Juan A; Zúñiga, Ángel; Bello, Yanis; Fabregat, Aleix B; Vicente, Ana I

    2016-09-01

    Glycated hemoglobin (Hb A 1c ) determination by multicapillary zone electrophoresis (MZE) can additionally be used to detect Hb A 2 , Hb F and most common hemoglobin (Hb) variants. We assessed the effectiveness of this method for detecting β-thalassemia (β-thal), δβ-thalassemia (δβ-thal) and most common Hb variants. Moreover, Hb F/Hb A 2 is evaluated as an index for discriminating between β- and δβ-thal traits. The theoretical β-thalassemia major (β-TM) birth rate in our healthcare area is calculated and contrasted with real data. A MZE technique was used for Hb A 1c measurements in 27,724 patients. Previous criteria for carrier detection were established and subsequently confirmed by molecular biology techniques. Positive predictive value (PPV) was 100.0%. The prevalence of β-thal trait (including δβ-thal) was 0.34%. The most prevalent mutations (estimated per 100,000 population) were HBB: c.118C > T (57.7%), HBB: c.93-21G>A (50.5%), HBB: c.92 + 1G > A (43.3%), HBB: c.92 + 6T > C (32.5%) and HBB: c.20delA (18.0%) for β-thalassemias, and Hb S (HBB: c.20A > T) (32.5%) and Hb J-Baltimore (HBB:c.3880T>A) (28.9%) for Hb variants. We found a paradoxical result between the theoretical β-TM birth rate and real data. We calculated an optimal Hb F/Hb A 2 index cutoff of 0.71 for discriminating between β- and δβ-thal traits. This method is highly cost-effective for detecting β-thalassemias and common Hb variants. Prevalence results match previous data for the Spanish population. Heterogeneity of mutations in Spain has markedly increased as a consequence of migration. The Hb F/Hb A 2 index cutoff could be used to predict δβ-thal trait.

  17. Transformation with TT8 and HB12 RNAi Constructs in Model Forage (Medicago sativa, Alfalfa) Affects Carbohydrate Structure and Metabolic Characteristics in Ruminant Livestock Systems.

    Science.gov (United States)

    Li, Xinxin; Zhang, Yonggen; Hannoufa, Abdelali; Yu, Peiqiang

    2015-11-04

    Lignin, a phenylpropanoid polymer present in secondary cell walls, has a negative impact on feed digestibility. TT8 and HB12 genes were shown to have low expression levels in low-lignin tissues of alfalfa, but to date, there has been no study on the effect of down-regulation of these two genes in alfalfa on nutrient chemical profiles and availability in ruminant livestock systems. The objectives of this study were to investigate the effect of transformation of alfalfa with TT8 and HB12 RNAi constructs on carbohydrate (CHO) structure and CHO nutritive value in ruminant livestock systems. The results showed that transformation with TT8 and HB12 RNAi constructs reduced rumen, rapidly degraded CHO fractions (RDCA4, P = 0.06; RDCB1, P alfalfa with TT8 and HB12 RNAi constructs induced molecular structure changes. Different CHO functional groups had different sensitivities and different responses to the transformation. The CHO molecular structure changes induced by the transformation were associated with predicted CHO availability. Compared with HB12 RNAi, transformation with TT8 RNAi could improve forage quality by increasing the availability of both NDF and DM. Further study is needed on the relationship between the transformation-induced structure changes at a molecular level and nutrient utilization in ruminant livestock systems when lignification is much higher.

  18. Molecular characterization of hemoglobin D Punjab traits and clinical-hematological profile of the patients

    Directory of Open Access Journals (Sweden)

    Sanjay Pandey

    Full Text Available CONTEXT AND OBJECTIVE: Hemoglobin (Hb D hemoglobinopathies are widespread diseases in northwestern India and usually present with mild hemolytic anemia and mild to moderate splenomegaly. The heterozygous form of Hb D is clinically silent, but coinheritance of Hb D with Hb S or beta-thalassemia produces clinically significant conditions like thalassemia intermedia of moderate severity. Under heterozygous conditions with coinheritance of alpha and beta-thalassemia, patients show a degree of clinical variability. Thus, our aim was to molecularly characterize the Hb D trait among individuals who were clinically symptomatic because of co-inheritance of alpha deletions or any beta-globin gene mutations. DESIGN AND SETTING: This was a cross-sectional study conducted in an autonomous tertiary-care hospital. METHODS: Complete blood count and red cell indices were measured using an automated cell analyzer. Quantitative assessment of hemoglobin Hb F, Hb A, Hb A2 and Hb D was performed by means of high performance liquid chromatography (HPLC. DNA extraction was done using the phenol-chloroform method. Molecular analyses on common alpha deletions and common beta mutations were done using the Gap polymerase chain reaction and Amplification Refractory Mutation System, respectively. RESULTS: We evaluated 30 patients and found clinical variation in the behavior of Hb D traits. In six patients, the Hb D traits were clinically symptomatic and behaved like those of thalassemia intermedia. Molecular characterization showed that three out of these six were IVS-1-5 positive. CONCLUSIONS: HPLC may not be the gold standard for diagnosing symptomatic Hb D Punjab traits. Hence, standard confirmation should include molecular studies.

  19. 2D-HB-Network at the air-water interface: A structural and dynamical characterization by means of ab initio and classical molecular dynamics simulations

    Science.gov (United States)

    Pezzotti, Simone; Serva, Alessandra; Gaigeot, Marie-Pierre

    2018-05-01

    Following our previous work where the existence of a special 2-Dimensional H-Bond (2D-HB)-Network was revealed at the air-water interface [S. Pezzotti et al., J. Phys. Chem. Lett. 8, 3133 (2017)], we provide here a full structural and dynamical characterization of this specific arrangement by means of both Density Functional Theory based and Force Field based molecular dynamics simulations. We show in particular that water at the interface with air reconstructs to maximize H-Bonds formed between interfacial molecules, which leads to the formation of an extended and non-interrupted 2-Dimensional H-Bond structure involving on average ˜90% of water molecules at the interface. We also show that the existence of such an extended structure, composed of H-Bonds all oriented parallel to the surface, constrains the reorientional dynamics of water that is hence slower at the interface than in the bulk. The structure and dynamics of the 2D-HB-Network provide new elements to possibly rationalize several specific properties of the air-water interface, such as water surface tension, anisotropic reorientation of interfacial water under an external field, and proton hopping.

  20. Beyond HbA1c.

    Science.gov (United States)

    Bloomgarden, Zachary

    2017-12-01

    It can scarcely be denied that the supreme goal of all theory is to make the irreducible basic elements as simple and as few as possible without having to surrender the adequate representation of a single datum of experience. The diaTribe Foundation convened a meeting on the topic of glycemic outcomes beyond HbA1c on 21 July 2017, in Bethesda (MD, USA), focusing on potential uses of continuous glucose monitoring (CGM). Understanding patterns of glycemia in people with diabetes has long been a focus of approaches to improving treatment, and over the past few years this has become an available modality for clinical practice. Glucose levels are not the only biologic parameters affecting HbA1c levels; HbA1c changes with anemia or, more subtly, with changes in rates of erythrocyte turnover not reflected in hemoglobin levels outside the normal range. Renal disease often is associated with lower HbA1c than would be predicted based on an individual's glycemic levels. Furthermore, HbA1c levels tend to increase with age and are higher in some ethnic groups; for example, people of African ethnicity have higher HbA1c levels than people of Northern European descent. Indeed, we have argued that even as a measure of mean glycemia HbA1c is inherently imprecise. Overall, for some 20% of people with diabetes, HbA1c levels are substantially higher, or substantially lower, than those that would be predicted from mean blood glucose levels. If one recognizes that HbA1c is, at best, a partial measure of mean glycemic exposure, one must surely accept that HbA1c does not reflect variability within a day, from day to day, and from period to period. Many glucose-lowering medicines, particularly the sulfonylureas and insulin, cause hypoglycemia, with consequent negative effects on quality of life and patient-reported outcomes, as well as association with weight gain and adverse macrovascular outcome; hypoglycemia will, of course, not be captured by HbA1c measurement. Based on these

  1. Hb Tianshui (HBB: C.119A > G) in Compound Heterozygosity with Hb S (HBB: C.20A > T) from Odisha, India.

    Science.gov (United States)

    Meher, Satyabrata; Dehury, Snehadhini; Mohanty, Pradeep Kumar; Patel, Siris; Pattanayak, Chinmayee; Bhattacharya, Subhra; Das, Kishalaya; Sarkar, Biswanath

    2016-08-01

    We describe here a rare β-globin gene variant, Hb Tianshui [β39(C5)Glu→Arg; HBB: c.119A > G], detected during routine screening in Odisha, India. This is the second report of Hb Tianshui and the first to describe the cation exchange high performance liquid chromatography (HPLC) and DNA studies of two cases of this variant. Both cases had coinherited Hb S (HBB: c.20A > T) but none presented with typical symptoms of sickle cell disease. One of the cases was heterozygous for a common α-thalassemia (α-thal) allele (-α(3.7)) (rightward) (NG_000006.1: g.34164_37967del3804) and marginally raised Hb F percentage, while the other Hb S/Hb Tianshui case was completely benign and healthy. An atypical Asian Indian haplotype [+ - + - +] could be assigned to the Hb Tianshui variant. Hb Tianshui seems to mimic a few other Hb variants in cation exchange HPLC. However, we report two specific patterns in the chromatograms that are characteristic to Hb Tianshui. Combining an alkaline electrophoresis result with cation exchange HPLC at screening would be preferred to detect this rare variant, especially in regions with considerable frequency of Hb E [β26(B8)Glu→Lys; HBB: c.79G > A] or Hb S.

  2. Simultaneous dual syringe electrospinning system using benign solvent to fabricate nanofibrous P(3HB-co-4HB)/collagen peptides construct as potential leave-on wound dressing

    International Nuclear Information System (INIS)

    Vigneswari, S.; Murugaiyah, V.; Kaur, G.; Abdul Khalil, H.P.S.; Amirul, A.A.

    2016-01-01

    The main focus of this study is the incorporation of collagen peptides to fabricate P(3-hydroxybutyrate-co-4-hydroxybutyrate) [P(3HB-co-4HB)] nano-fiber construct to further enhance surface wettability and support cell growth while harbouring desired properties for biodegradable wound dressing. Simultaneous electrospinning of nanofiber P(3HB-co-4HB)/collagen peptides construct was carried out using dual syringe system. The wettability of the constructs increased with the increase in 4HB molar fraction from 20 mol% 4HB [53.2°], P(3HB-co-35 mol%4HB)[48.9°], P(3HB-co-50 mol%4HB)[44.5°] and P(3HB-co-82 mol%4HB) [37.7°]. In vitro study carried out using mouse fibroblast cells (L929) grown on nanofiber P(3HB-co-4HB)/collagen peptides construct showed an increase in cell proliferation. In vivo study using animal model (Sprague Dawley rats) showed that nanofibrous P(3HB-co-4HB)/collagen peptides construct had a significant effect on wound contractions with the highest percentage of wound closure of 79%. Hence, P(3HB-co-4HB)/collagen peptides construct suitable for wound dressing have been developed using nano-fabrication technique. - Highlights: • Nano-fiber construct to enhance surface wettability and cell growth, harbouring desired properties as biodegradable wound dressing. • Simultaneous electrospinning of nanofiber P(3HB-co-4HB)/collagen construct using dual syringe system. • Nanofibrous construct accelerated wound healing with efficient cellular organization.

  3. Simultaneous dual syringe electrospinning system using benign solvent to fabricate nanofibrous P(3HB-co-4HB)/collagen peptides construct as potential leave-on wound dressing

    Energy Technology Data Exchange (ETDEWEB)

    Vigneswari, S. [Malaysian Institute of Pharmaceuticals and Nutraceuticals, NIBM, MOSTI, 11700 Penang (Malaysia); Institute of Marine Biotechnology, Universiti Malaysia Terengganu, 21030 Kuala Terengganu (Malaysia); Murugaiyah, V. [School of Pharmaceutical Sciences, Universiti Sains Malaysia, 11700 Penang (Malaysia); Kaur, G. [Institute of Research in Molecular Medicine, Universiti Sains Malaysia, 11700 Penang (Malaysia); Abdul Khalil, H.P.S. [School of Industrial Technology, Universiti Sains Malaysia, 11700 Penang (Malaysia); Amirul, A.A., E-mail: amirul@usm.my [Malaysian Institute of Pharmaceuticals and Nutraceuticals, NIBM, MOSTI, 11700 Penang (Malaysia); School of Biological Sciences, Universiti Sains Malaysia, 11800 Penang (Malaysia); Centre of Chemical Biology, Universiti Sains Malaysia, 11900 Penang (Malaysia)

    2016-09-01

    The main focus of this study is the incorporation of collagen peptides to fabricate P(3-hydroxybutyrate-co-4-hydroxybutyrate) [P(3HB-co-4HB)] nano-fiber construct to further enhance surface wettability and support cell growth while harbouring desired properties for biodegradable wound dressing. Simultaneous electrospinning of nanofiber P(3HB-co-4HB)/collagen peptides construct was carried out using dual syringe system. The wettability of the constructs increased with the increase in 4HB molar fraction from 20 mol% 4HB [53.2°], P(3HB-co-35 mol%4HB)[48.9°], P(3HB-co-50 mol%4HB)[44.5°] and P(3HB-co-82 mol%4HB) [37.7°]. In vitro study carried out using mouse fibroblast cells (L929) grown on nanofiber P(3HB-co-4HB)/collagen peptides construct showed an increase in cell proliferation. In vivo study using animal model (Sprague Dawley rats) showed that nanofibrous P(3HB-co-4HB)/collagen peptides construct had a significant effect on wound contractions with the highest percentage of wound closure of 79%. Hence, P(3HB-co-4HB)/collagen peptides construct suitable for wound dressing have been developed using nano-fabrication technique. - Highlights: • Nano-fiber construct to enhance surface wettability and cell growth, harbouring desired properties as biodegradable wound dressing. • Simultaneous electrospinning of nanofiber P(3HB-co-4HB)/collagen construct using dual syringe system. • Nanofibrous construct accelerated wound healing with efficient cellular organization.

  4. Interação entre Hb C [beta6(A3Glu>Lys] e IVS II-654 (C>T beta-talassemia no Brasil Hb C [beta6(A3Glu>Lys] and IVS II - 654 (C>T beta thalassemia interaction in Brazil

    Directory of Open Access Journals (Sweden)

    Claudia R. Bonini-Domingos

    2003-06-01

    Full Text Available Thalassemias are a heterogeneous group of inherited disorders characterized by a microcytic hypochromic anemia and an imbalance in the synthesis of the globin-chains. Hb C is the second most frequently variant of hemoglobin found in Brazil. The laboratory diagnosis of hemoglobinopathies, including thalassemias, is growing in importance, particularly because of an increasing requirement for neonatal diagnosis of abnormal hemoglobins. Screening tests were carried out using alkaline and acid electrophoresis, globin-chain analysis by cellulose acetate in alkaline pH, isoelectric focusing and HPLC. The molecular characterization was made by PCR-ASO for Hb C and beta thalassemia mutants. Large-scale screening and discriminative methodologies must provide information about the hemoglobin polymorphisms in Brazilian population. HPLC is a powerful tool in these cases. Molecular characterization is important to genetic counseling and clinical management, in particular for the Brazilian population that have an intense racial admixture, with great variability of hemoglobins. In this paper an association between Hb C and beta thalassemia (IVS-II-654 in a black family from Brazil was described.

  5. Measurements of red cell deformability and hydration reflect HbF and HbA2 in blood from patients with sickle cell anemia.

    Science.gov (United States)

    Parrow, Nermi L; Tu, Hongbin; Nichols, James; Violet, Pierre-Christian; Pittman, Corinne A; Fitzhugh, Courtney; Fleming, Robert E; Mohandas, Narla; Tisdale, John F; Levine, Mark

    2017-06-01

    Decreased erythrocyte deformability, as measured by ektacytometry, may be associated with disease severity in sickle cell anemia (SCA). Heterogeneous populations of rigid and deformable cells in SCA blood result in distortions of diffraction pattern measurements that correlate with the concentration of hemoglobin S (HbS) and the percentage of irreversibly sickled cells. We hypothesize that red cell heterogeneity, as well as deformability, will also be influenced by the concentration of alternative hemoglobins such as fetal hemoglobin (HbF) and the adult variant, HbA 2 . To test this hypothesis, we investigate the relationship between diffraction pattern distortion, osmotic gradient ektacytometry parameters, and the hemoglobin composition of SCA blood. We observe a correlation between the extent of diffraction pattern distortions and percentage of HbF and HbA 2 . Osmotic gradient ektacytometry data indicate that minimum elongation in the hypotonic region is positively correlated with HbF, as is the osmolality at which it occurs. The osmolality at both minimum and maximum elongation is inversely correlated with HbS and HbA 2 . These data suggest that HbF may effectively improve surface-to-volume ratio and osmotic fragility in SCA erythrocytes. HbA 2 may be relatively ineffective in improving these characteristics or cellular hydration at the levels found in this patient cohort. Copyright © 2017. Published by Elsevier Inc.

  6. Four adult hemoglobin types in one mulatto family Quatro tipos de hemoglobina em uma família adulta de mulatos

    Directory of Open Access Journals (Sweden)

    João Targino de Araújo

    1996-06-01

    Full Text Available The studied family showed the presence of four different types of hemoglobin. The family member who gave rise to this study (=propositus presented Hb C and the hybrid Hb CG-phila. The propositus has three children, all of which have Hb AC; none of the family members showed any clinical symptoms. The investigation of the hemoglobin arose from the finding of target red cells in a blood test done during the pre-operatory examination for lower limb varicose vein stripping. The hybrid Hb CG-phila is due to two gene pairs, each of which with individual expression, determining the synthesis and the particular type subunits. The hybrid Hb CG-phila is formed by the combination velocity of the subunits alpha2G-philabeta2; therefore the proportion of the hybrid Hb CG-phila is lower than Hb G-phila and Hb C. The identification and molecular characterization of Hb G-phila showed the position alpha268 Asn->Lys beta2 and Hb C showed alpha2beta26 Glu->Lys.A família em estudo mostrou a presença de quatro diferentes tipos de hemoglobinas. O membro da família que deu origem ao estudo (propositus foi identificado como Hb C e o híbrido com Hb CG-phila. O propositus tem três filhos todos portadores de Hb AC; nenhum membro da família apresentou sintomas clínicos. A pesquisa da hemoglobina resultou da existência de hemácias em alvo, no pré-operatório de varizes de membros inferiores. O híbrido Hb CG-phila é constituído por dois pares de genes, mas cada um com expressão inidividual, determinando a síntese e o tipo particular das subunidades. O híbrido Hb CG-phila é formado pela velocidade de combinação das subunidades alfa2G-philabeta2C assim sendo a proporção do híbrido Hb CG-phila é menor do que a Hb G-phila e Hb C. A identificação e caracterização molecular da Hb G-phila mostrou a posição alfa268 Asn->Lys beta2 a Hb C alfa2beta26 Glu->Lys.

  7. Caracterização da interação de inositol hexafosfato e cloreto com hemoglobina humana: aspectos energéticos e estruturais

    OpenAIRE

    Silva, Vanessa de Cássia Teixeira da [UNESP

    2010-01-01

    A ligação do O2 à Hemoglobina (Hb) é um processo regulado por interações alostéricas. Os íons Inositol hexafosfato (IHP) e cloreto, e prótons, são efetores alostéricos que estabilizam a Hb na estrutura quaternária T, diminuindo a afinidade da proteina pelo O2 em meio alcalino. A ligação de IHP também altera a cooperatividade de algumas hemoglobinas como, por exemplo a hemoglobina desArg, uma variante da HbAo da qual o resíduo arginina 141 das cadeia alfas foram retirados enzimaticamente. Esta...

  8. Drugs affecting HbA1c levels

    Directory of Open Access Journals (Sweden)

    Ranjit Unnikrishnan

    2012-01-01

    Full Text Available Glycated hemoglobin (HbA1c is an important indicator of glycemic control in diabetes mellitus, based on which important diagnostic and therapeutic decisions are routinely made. However, there are several situations in which the level of HbA1c may not faithfully reflect the glycemic control in a given patient. Important among these is the use of certain non-diabetic medications, which can affect the HbA1c levels in different ways. This review focuses on the non-diabetic medications which can inappropriately raise or lower the HbA1c levels, and the postulated mechanisms for the same.

  9. [About the HbA1c in the elderly].

    Science.gov (United States)

    Farcet, Anaïs; Delalande, Géraldine; Oliver, Charles; Retornaz, Frédérique

    2016-03-01

    HbA1c product of non enzymatic glycation of HbA increases in relation with the mean blood glucose level during the former 2-3 months. HbA1c levels are correlated with the development of diabetic complications and HbA1c assessment is now the gold standard for evaluation of diabetes control. HbA1c level should not be higher than 7% to avoid these complications. However, in aged peoples, the objectives of diabetes control vary according to their health status. It must be good with HbA1c lower than 7-7.5% in healthy subjects and more relax in subjects with symptoms of frailty and risks of non perceived and self corrected hypoglycemia. Under these conditions, HbA1c values lower than 8 to 9% are advised. Nevertheless, hypoglycemia episodes may occur in patients with high HbA1c and capillary glucose follow-up is necessary for detection of such complications.

  10. Detection of Hb Constant Spring (HBA2: c.427T>C) Heterozygotes in Combination with β-Thalassemia or Hb E Trait by Capillary Electrophoresis.

    Science.gov (United States)

    Pornprasert, Sakorn; Saoboontan, Supansa; Punyamung, Manoo

    2015-01-01

    Hb Constant Spring (Hb CS; HBA2: c.427T>C) is often missed by routine laboratory testing as its mRNA as well as gene product are unstable and presented at a low level in peripheral blood. This study aimed to analyze the efficacy of capillary electrophoresis (CE) for detecting and quantifying of Hb CS in β-thalassemia (β-thal) trait or Hb E (HBB: c.79G>A) trait samples with reduced β-globin chain expression. Thalassemia diagnostic data were reviewed in 2524 blood samples that were submitted to the laboratory of the Associated Medical Sciences Clinical Service Center, Chiang Mai, Thailand for hemoglobinopathy and thalassemia diagnosis. DNA analysis for Hb CS was performed in 322 β-thal trait and 397 Hb E trait samples using the amplification refractory mutation system (ARMS). The CE electropherogram of Hb CS at zone 2 was observed in all five samples with β-thal trait and nine samples with Hb E trait with levels varying from 0.1-2.8 and 0.1-2.3%, respectively. Thus, the CE method proved useful for screening of Hb CS in samples with β-thal trait or Hb E trait, which is essential for providing accurate diagnosis, genetic counseling, prevention and control programs of Hb H-CS disease.

  11. Inhibition of Hb Binding to GP1bα Abrogates Hb-Mediated Thrombus Formation on Immobilized VWF and Collagen under Physiological Shear Stress.

    Science.gov (United States)

    Annarapu, Gowtham K; Singhal, Rashi; Peng, Yuandong; Guchhait, Prasenjit

    2016-01-01

    Reports including our own describe that intravascular hemolysis increases the risk of thrombosis in hemolytic disorders. Our recent study shows that plasma Hb concentrations correlate directly with platelet activation in patients with paroxysmal nocturnal hemoglobinuria (PNH). The binding of Hb to glycoprotein1bα (GP1bα) increases platelet activation. A peptide AA1-50, designed from N-terminal amino acid sequence of GP1bα significantly inhibits the Hb binding to GP1bα as well as Hb-induced platelet activation. This study further examined if the Hb-mediated platelet activation plays any significant role in thrombus formation on subendothelium matrix under physiological flow shear stresses and the inhibition of Hb-platelet interaction can abrogate the above effects of Hb. Study performed thrombus formation assay in vitro by perfusing whole blood over immobilized VWF or collagen type I in presence of Hb under shear stresses simulating arterial or venous flow. The Hb concentrations ranging from 5 to 10 μM, commonly observed level in plasma of the hemolytic patients including PNH, dose-dependently increased thrombus formation on immobilized VWF under higher shear stress of 25 dyne/cm2, but not at 5 dyne/cm2. The above Hb concentrations also increased thrombus formation on immobilized collagen under both shear stresses of 5 and 25 dyne/cm2. The peptide AA1-50 abrogated invariably the above effects of Hb on thrombus formation. This study therefore indicates that the Hb-induced platelet activation plays a crucial role in thrombus formation on immobilized VWF or collagen under physiological flow shear stresses. Thus suggesting a probable role of this mechanism in facilitating thrombosis under hemolytic conditions.

  12. Efeitos do exercicio físico em parâmetros moleculares da via de sinalização da insulina e obesidade

    Directory of Open Access Journals (Sweden)

    Joni Marcio de Farias

    2014-08-01

    Full Text Available http://dx.doi.org/10.5007/1980-0037.2014v16n5p588 A prevalência da obesidade e diabetes mellitus tem aumentado significativamente nos últimos anos e o conhecimento de que o tecido adiposo tem atividade endócrina e desempenha funções importantes na regulação da inflamação e no metabolismo energético por meio de mecanismos moleculares entre outros é fonte de novas pesquisas. Este trabalho versa sobre os mecanismos moleculares envolvidos na obesidade e diabetes principalmente em tecidos periféricos bem como a relação do exercício físico neste contexto, em forma de revisão bibliográfica. A metodologia foi levantamento bibliográfico nas principais bases de dados: Scielo e PubMed, publicados no período de 1998 a 2012. Os estudos tem demonstrado uma inter-relação entre os mecanismos moleculares envolvidos no desenvolvimento da obesidade e diabetes em tecidos periféricos e centrais. Do ponto de vista do exercício físico, vários estudos demonstram uma contribuição muito grande na diminuição da prevalência, no controle e até mesmo no tratamento da obesidade e diabetes. No entanto há necessidade de estudos mais aprofundados relacionando diversos tipos de exercício físico, em volumes e intensidades diferentes e preferencialmente com humanos, bem como o modelo de estudo, que quando utilizado animais, os programas de exercício devem ser desenvolvidos concomitantemente com alimentação rica em gordura, verificando mais intensamente o exercício físico e o seu real papel na prevenção destas doenças.

  13. Pregnancy outcome in patients with sickle cell disease in the UK--a national cohort study comparing sickle cell anaemia (HbSS) with HbSC disease.

    Science.gov (United States)

    Oteng-Ntim, Eugene; Ayensah, Benjamin; Knight, Marian; Howard, Jo

    2015-04-01

    We describe the findings from a national study of maternal and fetal outcomes of pregnancy in women with sickle cell disease (SCD). Data were collected via the United Kingdom Obstetric Surveillance System between 1 February 2010 and 31 January 2011 from 109 women, of whom 51 (46·8%) had HbSS and 44 (40·4%) had HbSC. Data included antenatal, maternal and fetal outcomes. Comparisons were made between women with HbSS and HbSC. Incidence of complications were acute pain (57%), blood transfusion (26%), urinary tract infection (UTI; 12%) and critical care unit admission (23%) and these were all more common in women with HbSS than HbSC. There was no difference in the incidence of acute chest syndrome, hypertension and venous thromboembolism between HbSS and HbSC. Women with HbSS were more likely to deliver at pregnancy. © 2014 John Wiley & Sons Ltd.

  14. Hb D/Talassemia beta associada à anemia crônica Hb D/ Beta thalassaemia associated with chronic anaemia

    Directory of Open Access Journals (Sweden)

    Paulo C. Naoum

    2002-03-01

    Full Text Available We describe a case of Hb D/Beta thalassemia associated with chronic anemia. Hematological analyses performed in a patient with chronic anemia demonstrating microcytosis and hypochromic in his erythrocytes. Specific laboratory diagnosis performed by alkaline and acid electrophoresis, and fetal determination by alkali resistance, indicated it to be Hb D associated with beta thalassemia. Analyses carried out on his family (father, mother and brother confirmed the suspected diagnosis. Hb D/Beta thalassemia is a very rare interaction in the Brazilian population, and its determination required specific laboratorial techniques and hematological analyses.

  15. Role of Hydroxamate-Based Histone Deacetylase Inhibitors (Hb-HDACIs) in the Treatment of Solid Malignancies

    Energy Technology Data Exchange (ETDEWEB)

    Grassadonia, Antonino [Department of Experimental and Clinical Sciences, University ’G. d’Annunzio’, I-66013 Chieti (Italy); Cioffi, Pasquale; Simiele, Felice [Hospital Pharmacy, “SS. Annunziata” Hospital, I-66013 Chieti (Italy); Iezzi, Laura; Zilli, Marinella [Oncology Department, “SS. Annunziata” Hospital, I-66013 Chieti (Italy); Natoli, Clara, E-mail: natoli@unich.it [Department of Experimental and Clinical Sciences, University ’G. d’Annunzio’, I-66013 Chieti (Italy)

    2013-07-25

    Hydroxamate-based histone deacetylase inhibitors (Hb-HDACIs), such as vorinostat, belinostat and panobinostat, have been previously shown to have a wide range of activity in hematologic malignancies such as cutaneous T-cell lymphoma and multiple myeloma. Recent data show that they synergize with a variety of cytotoxic and molecular targeted agents in many different solid tumors, including breast, prostate, pancreatic, lung and ovarian cancer. Hb-HDACIs have a quite good toxicity profile and are now being tested in phase I and II clinical trials in solid tumors with promising results in selected neoplasms, such as hepatocarcinoma. This review will focus on their clinical activity and safety in patients with advanced solid neoplasms.

  16. Role of Hydroxamate-Based Histone Deacetylase Inhibitors (Hb-HDACIs) in the Treatment of Solid Malignancies

    International Nuclear Information System (INIS)

    Grassadonia, Antonino; Cioffi, Pasquale; Simiele, Felice; Iezzi, Laura; Zilli, Marinella; Natoli, Clara

    2013-01-01

    Hydroxamate-based histone deacetylase inhibitors (Hb-HDACIs), such as vorinostat, belinostat and panobinostat, have been previously shown to have a wide range of activity in hematologic malignancies such as cutaneous T-cell lymphoma and multiple myeloma. Recent data show that they synergize with a variety of cytotoxic and molecular targeted agents in many different solid tumors, including breast, prostate, pancreatic, lung and ovarian cancer. Hb-HDACIs have a quite good toxicity profile and are now being tested in phase I and II clinical trials in solid tumors with promising results in selected neoplasms, such as hepatocarcinoma. This review will focus on their clinical activity and safety in patients with advanced solid neoplasms

  17. Role of Hydroxamate-Based Histone Deacetylase Inhibitors (Hb-HDACIs in the Treatment of Solid Malignancies

    Directory of Open Access Journals (Sweden)

    Marinella Zilli

    2013-07-01

    Full Text Available Hydroxamate-based histone deacetylase inhibitors (Hb-HDACIs, such as vorinostat, belinostat and panobinostat, have been previously shown to have a wide range of activity in hematologic malignancies such as cutaneous T-cell lymphoma and multiple myeloma. Recent data show that they synergize with a variety of cytotoxic and molecular targeted agents in many different solid tumors, including breast, prostate, pancreatic, lung and ovarian cancer. Hb-HDACIs have a quite good toxicity profile and are now being tested in phase I and II clinical trials in solid tumors with promising results in selected neoplasms, such as hepatocarcinoma. This review will focus on their clinical activity and safety in patients with advanced solid neoplasms.

  18. Can the Afinion HbA1c Point-of-Care instrument be an alternative method for the Tosoh G8 in the case of Hb-Tacoma?

    Science.gov (United States)

    Lenters-Westra, Erna; Strunk, Annuska; Campbell, Paul; Slingerland, Robbert J

    2017-02-01

    Hb-variant interference when reporting HbA1c has been an ongoing challenge since HbA1c was introduced to monitor patients with diabetes mellitus. Most Hb-variants show an abnormal chromatogram when cation-exchange HPLC is used for the determination of HbA1c. Unfortunately, the Tosoh G8 generates what appears to be normal chromatogram in the presence of Hb-Tacoma, yielding a falsely high HbA1c value. The primary aim of the study was to investigate if the Afinion HbA1c point-of-care (POC) instrument could be used as an alternative method for the Tosoh G8 when testing for HbA1c in the presence of Hb-Tacoma. Whole blood samples were collected in K 2 EDTA tubes from individuals homozygous for HbA (n = 40) and heterozygous for Hb-Tacoma (n = 20). Samples were then immediately analyzed with the Afinion POC instrument. After analysis, aliquots of each sample were frozen at -80 °C. The frozen samples were shipped on dry ice to the European Reference Laboratory for Glycohemoglobin (ERL) and analyzed with three International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) and National Glycohemoglobin Standardization Program (NGSP) Secondary Reference Measurement Procedures (SRMPs). The Premier Hb9210 was used as the reference method. When compared to the reference method, samples with Hb-Tacoma yielded mean relative differences of 31.8% on the Tosoh G8, 21.5% on the Roche Tina-quant Gen. 2 and 16.8% on the Afinion. The Afinion cannot be used as an alternative method for the Tosoh G8 when testing for HbA1c in the presence of Hb-Tacoma.

  19. HB-Line Plutonium Oxide Data Collection Strategy

    Energy Technology Data Exchange (ETDEWEB)

    Watkins, R. [Savannah River Nuclear Solutions; Varble, J. [Savannah River Nuclear Solutions; Jordan, J. [Savannah River Nuclear Solutions

    2015-05-26

    HB-Line and H-Canyon will handle and process plutonium material to produce plutonium oxide for feed to the Mixed Oxide Fuel Fabrication Facility (MFFF). However, the plutonium oxide product will not be transferred to the MFFF directly from HB-Line until it is packaged into a qualified DOE-STD-3013-2012 container. In the interim, HB-Line will load plutonium oxide into an inner, filtered can. The inner can will be placed in a filtered bag, which will be loaded into a filtered outer can. The outer can will be loaded into a certified 9975 with getter assembly in compliance with onsite transportation requirement, for subsequent storage and transfer to the K-Area Complex (KAC). After DOE-STD-3013-2012 container packaging capabilities are established, the product will be returned to HB-Line to be packaged into a qualified DOE-STD-3013-2012 container. To support the transfer of plutonium oxide to KAC and then eventually to MFFF, various material and packaging data will have to be collected and retained. In addition, data from initial HB-Line processing operations will be needed to support future DOE-STD-3013-2012 qualification as amended by the HB-Line DOE Standard equivalency. As production increases, the volume of data to collect will increase. The HB-Line data collected will be in the form of paper copies and electronic media. Paper copy data will, at a minimum, consist of facility procedures, nonconformance reports (NCRs), and DCS print outs. Electronic data will be in the form of Adobe portable document formats (PDFs). Collecting all the required data for each plutonium oxide can will be no small effort for HB-Line, and will become more challenging once the maximum annual oxide production throughput is achieved due to the sheer volume of data to be collected. The majority of the data collected will be in the form of facility procedures, DCS print outs, and laboratory results. To facilitate complete collection of this data, a traveler form will be developed which

  20. Low oxygen saturation and severe anemia in compound heterozygous Hb Louisville [β42(CD1)Phe→Leu] and Hb La Desirade [β129(H7)Ala→Val].

    Science.gov (United States)

    Kamseng, Parin; Trakulsrichai, Satariya; Trachoo, Objoon; Yimniam, Walaiporn; Panthan, Bhakbhoom; Jittorntam, Paisan; Niparuck, Pimjai; Sanguanwit, Pitsucha; Wananukul, Winai; Jindadamrongwech, Sumalee

    2017-03-01

    To investigate the cause(s) of a Thai male proband presenting low oxygen saturation by pulse oximetry (SpO 2 ) and severe anemia. As Hb variant was suspected, Hb typing was determined by high-performance liquid chromatography and capillary electrophoresis, and subsequently Hb variant was identified by DNA sequencing. Complete blood counts were performed using automated blood cell counter and oxygen saturation was measured by pulse oximetry. Proband was compound heterozygous for Hb Louisville [β42(CD1)Phe→Leu] and Hb La Desirade [β129(H7)Ala→Val]. Of the proband's two sons, one was compound heterozygous for Hb Louisville and Hb E and the other for Hb La Desirade and Hb E. The former son had similar clinical features and laboratory findings with those of the proband while the latter showed had no abnormal clinical manifestations. This the first report of compound heterozygosity of Hb Louisville and Hb La Desirade in an individual of Southeast Asian ethnicity. Hb variant identification is crucial for genetic counseling and appropriate treatment in regions where hemoglobinopathies are common.

  1. Prevalence and molecular characterization of abnormal hemoglobin in eastern Guangdong of southern China.

    Science.gov (United States)

    Lin, M; Wang, Q; Zheng, L; Huang, Y; Lin, F; Lin, C P; Yang, L Y

    2012-02-01

    Abnormal hemoglobins (Hbs) are the most commonly inherited disorders in humans. Their frequency and types change considerably with geographic location and ethnic group. To investigate the molecular epidemiological characterization of abnormal Hbs in eastern Guangdong of southern China, a total of 11,450 'healthy' subjects were subjected to hemoglobin electrophoresis screening. Samples of EDTA-K(2) blood with abnormal Hbs were analyzed by CELL-DYN1700 blood analyzer; thalassemia genotypes and Hb E variant were identified by gap-PCR and/or reverse dot blot (RDB). The genotypes of Hb variants were detected by PCR and sequencing. The incidence of abnormal Hbs was 0.358%(41/11,450) in Chaozhou, including 12.2% (5/41) Hb J, 4.9% (2/41) Hb K, 9.7% (4/41) Hb Q, 31.7% (13/41) Hb G/D and 41.5% (17/41) Hb E. Eight types of Hb variants were found, including 3 cases of Hb J-Bangkok, 2 cases of Hb J-Wenchang-Wuming, 2 cases of Hb New York, 4 cases of Hb Q-Thailand, 5 cases of Hb G-Waimanalo, 4 cases of Hb Ottawa, 4 cases of Hb G-Chinese and 17 cases of Hb E. In comparison with other areas of Guangdong, Chaozhou had a different pattern of abnormal Hbs with a high prevalence of Hb G/D. This study describes the prevalence and molecular characterization of abnormal Hbs in eastern Guangdong. © 2011 John Wiley & Sons A/S.

  2. Hb Dartmouth (HBA2: c.200T>C): An α2-Globin Gene Associated with Hb H Disease in One Homozygous Patient.

    Science.gov (United States)

    Farashi, Samaneh; Faramarzi Garous, Negin; Ashki, Mehri; Vakili, Shadi; Zeinali, Fatemah; Imanian, Hashem; Azarkeivan, Azita; Najmabadi, Hossein

    2015-01-01

    Hb H (β4) disease is caused by deletion or inactivation of three out of four α-globin genes. A high incidence of Hb H disease has been reported all over the world. There is a wide spectrum of phenotypic presentations, from clinically asymptomatic to having significant hepatosplenomegaly and requiring occasional or even regular blood transfusions, even more severe anemia, Hb Bart's (γ4) hydrops fetalis syndrome that can cause death in the affected fetuses late in gestation. We here present a case who was diagnosed with Hb H disease that represents a new genotype for this hereditary disorder. Hb Dartmouth is a variant caused by a missense mutation at codon 66 of the α2-globin gene (HBA2: c.200T>C), resulting in the substitution of leucine by proline. We here emphasize the importance of this point mutation involving Hb H disease and also the necessity for prenatal diagnosis (PND) for those who carry this point mutation in the heterozygous state.

  3. Secondary polycythaemia in a Malay girl with homozygous Hb Tak.

    Science.gov (United States)

    Amran, H S; Aziz, M A; George, E; Mahmud, N; Lee, T Y; Md Noor, S

    2017-12-01

    Hb Tak is one of more than 200 high affinity haemoglobin variants reported worldwide. It results from the insertion of two nucleotides (AC) at the termination codon, between codon 146 and codon 147 of the beta-globin gene [Beta 147 (+AC)]. Polycythaemia is the main clinical feature although affected carriers are usually asymptomatic and do not require intervention. Several case studies in this region have reported the co-inheritance of Hb Tak with Hb E, delta beta and beta thalassaemia with one case of homozygous Hb Tak in a Thai boy. In this case report, a cluster of haemoglobin Tak was found in a family of Malay ethnic origin. Cascade family screening was conducted while investigating a 4-year old girl who presented with symptomatic polycythaemia. She had 2 previous Hb analysis done, at 7-month and 2-year-old with the diagnosis of possible Hb Q Thailand and Homozygous Hb D, respectively. Both diagnosis did not fit her clinical presentations. She was plethoric, had reduced exercise tolerance as well as cardiomyopathy. Her parents were consanguineously married and later diagnosed as asymptomatic carriers of Hb Tak. Consequently, re-analysis of the girl's blood sample revealed a homozygous state of Hb Tak. In conclusion, high oxygen affinity haemoglobin like Hb Tak should be considered in the investigation of polycythaemic patients with abnormal Hb analyses. In this case, DNA analysis was crucial in determining the correct diagnosis.

  4. A Clinical Update of the Hb Siirt [β27(B9)Ala→Gly; HBB: c.83C>G] Hemoglobin Variant.

    Science.gov (United States)

    Cappabianca, Maria Pia; Colosimo, Alessia; Sabatucci, Annalaura; Dainese, Enrico; Di Biagio, Paola; Piscitelli, Roberta; Sarra, Ofelia; Zei, Daniela; Amato, Antonio

    2017-01-01

    We report a clinical update of the hemoglobin (Hb) variant [β27(B9)Ala→Gly; HBB: c.83C>G], named Hb Siirt, that was previously described as a silent variant in a 23-year-old Kurdish female. The patient was also a carrier of the codon 5 (-CT) (HBB: c.17_18delCT) frameshift mutation and of the ααα anti 3.7 triplication. Her initial moderate β-thalassemia intermedia (β-TI) phenotype worsened with time, causing the patient to become a transfusion-dependent subject at the age of ∼40 years. Subsequent molecular characterization of both parents revealed that the Hb Siirt variant was inherited by the mother, while the other two globin alterations (HBB: c.17_18delCT and ααα anti 3.7 triplication) were genetically transmitted by the father. The latter remained a carrier of a mild β-TI phenotype throughout his life, at least until the age of 65 years. We hypothesize that the worsened clinical conditions in the daughter were due to the additional, maternally inherited Hb Siirt variant. However, protein 3D conformational analysis did not seem to reveal substantial overall structural changes. Among the other three described variants [Hb Volga (HBB: c.83C>A), Hb Knossos (HBB: c.82 G>T), Hb Grange-Blanche (HBB: c.83C>T] that are due to nucleotide substitutions at codon 27 of the β-globin gene; only Hb Knossos causes a β + -thalassemia (β + -thal) phenotype.

  5. A method comparison study between two hemoglobinometer models (Hemocue Hb 301 and Hb 201+) to measure hemoglobin concentrations and estimate anemia prevalence among women in Preah Vihear, Cambodia.

    Science.gov (United States)

    Rappaport, A I; Karakochuk, C D; Whitfield, K C; Kheang, K M; Green, T J

    2017-02-01

    Hemoglobin (Hb) concentration is often measured in global health and nutrition surveys to determine anemia prevalence using a portable hemoglobinometer such as the Hemocue® Hb 201+. More recently, a newer model was released (Hemocue Hb 301) utilizing slightly different methods to measure Hb as compared to the older model. The objective was to measure bias and concordance between Hb concentrations using the Hemocue Hb 301 and Hb 201+ models in a rural field setting. Hemoglobin (Hb) concentration was measured using one finger prick of blood (approximately 10 μL) from 175 Cambodian women (18-49 years) using three Hemocue Hb 201+ and three Hb 301 machines. Bias and concordance were measured and plotted. Overall, mean ± SD Hb concentration was 116 ± 13 g/L using the Hb 201+ and 118 ± 12 g/L using the Hb 301; and anemia prevalence (Hb < 120 g/L) was 58% (n = 102) and 58% (n = 101), respectively. Overall bias ± SD was 2.0 ± 10.5 g/L and concordance (95% CI) was 0.63 (0.54, 0.72). Despite the 2 g/L bias detected between models, anemia prevalence was very similar in both models. The two models measured anemia prevalence comparably in this population of women in rural Cambodia. © 2016 John Wiley & Sons Ltd.

  6. Current Status of HbA1c Biosensors

    Science.gov (United States)

    Lin, Hua; Yi, Jun

    2017-01-01

    Glycated hemoglobin (HbA1c) is formed via non-enzymatic glycosylation reactions at the α–amino group of βVal1 residues in the tetrameric Hb, and it can reflect the ambient glycemic level over the past two to three months. A variety of HbA1c detection methods, including chromatography, immunoassay, enzymatic measurement, electrochemical sensor and capillary electrophoresis have been developed and used in research laboratories and in clinics as well. In this review, we summarize the current status of HbA1c biosensors based on the recognition of the sugar moiety on the protein and also their applications in the whole blood sample measurements. PMID:28777351

  7. The sunflower transcription factor HaHB11 confers tolerance to water deficit and salinity to transgenic Arabidopsis and alfalfa plants.

    Science.gov (United States)

    Cabello, Julieta V; Giacomelli, Jorge I; Gómez, María C; Chan, Raquel L

    2017-09-10

    Homeodomain-leucine zipper (HD-Zip) transcription factors are unique to the plant kingdom; members of subfamily I are known to be involved in abiotic stress responses. HaHB11 belongs to this subfamily and it was previously shown that it is able to confer improved yield and tolerance to flooding via a quiescent strategy. Here we show that HaHB11 expression is induced by ABA, NaCl and water deficit in sunflower seedlings and leaves. Arabidopsis transgenic plants expressing HaHB11, controlled either by its own promoter or by the constitutive 35S CaMV, presented rolled leaves and longer roots than WT when grown under standard conditions. In addition, these plants showed wider stems and more vascular bundles. To deal with drought, HaHB11 transgenic plants closed their stomata faster and lost less water than controls, triggering an enhanced tolerance to such stress condition and also to salinity stress. Concomitantly, ABA-synthesis and sensing related genes were differentially regulated in HaHB11 transgenic plants. Either under long-term salinity stress or mild drought stress, HaHB11 transgenic plants did not exhibit yield penalties. Moreover, alfalfa transgenic plants were generated which also showed enhanced drought tolerance. Altogether, the results indicated that HaHB11 was able to confer drought and salinity tolerance via a complex mechanism which involves morphological, physiological and molecular changes. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Transfusion Associated Peak in Hb HPLC Chromatogram – a Case Report

    Science.gov (United States)

    Jain, Sonal; Dass, Jasmita; Pati, Hara Prasad

    2012-01-01

    High performance liquid chromatography (HPLC) and electrophoresis are commonly used to diagnose various hemoglobinopathies. However, insufficient information about the transfusion history can lead to unexpected and confusing results. We are reporting a case of Juvenile myelomonocytic leukemia (JMML) in which HbHPLC was done to quantify fetal hemoglobin (HbF). The chromatogram showed elevated HbF along with a peak in the HbD window. A transfusion acquired peak was suspected based on the unexpectedly low percentage of HbD and was subsequently confirmed using parental HbHPLC. PMID:22348188

  9. Hb H Hydrops Fetalis Syndrome Caused by Association of the - -(SEA) Deletion and Hb Constant Spring (HBA2: c.427T > C) Mutation in a Chinese Family.

    Science.gov (United States)

    He, Sheng; Zheng, Chenguang; Meng, Dahua; Chen, Rongyu; Zhang, Qiang; Tian, Xiaoxian; Chen, Shaoke

    2015-01-01

    Hb Constant Spring (Hb CS; HBA2: c.427T > C) is an unstable hemoglobin (Hb) variant that results from a nucleotide substitution at the termination codon of the α2-globin gene. Compound heterozygosity for α(0)-thalassemia (α(0)-thal) and Hb CS (- -(SEA)/α(CS)α) results in Hb H/Hb CS disease, which is generally characterized with mild hemolytic anemia, jaundice, and splenomegaly. Here, we describe one case with Hb H/Hb CS disease that presented with fetal anemia and fetal hydrops, known as Hb H (β4) hydrops fetalis. This is the first report of fetal hydrops caused by association of the - -(SEA) deletion and the α(CS)α mutation. Our study highlights the significance of watchful observation using a serial ultrasound method and care of pregnant women who have fetuses found to carry Hb H/Hb CS disease during pregnancy, to guard against the occurrence of fetal hydrops.

  10. How does CKD affect HbA1c?

    Science.gov (United States)

    Bloomgarden, Zachary; Handelsman, Yehuda

    2018-04-01

    HOW DOES CHRONIC KIDNEY DISEASE AFFECT HBA1C?: A number of factors determine HbA1c other than the level of glucose exposure alone. In an subset analysis of the Atherosclerosis Risk in Communities study of 941 diabetic people with varying degrees of chronic kidney disease (CKD), as well as 724 who did not have CKD, and mean age in the eighth decade, Jung et al. ask whether HbA1c is reliable as an indicator of glycemia in people with kidney disease (CKD) to the same degree as in those not having kidney disease, and, if not, whether measures of glycated serum proteins may be more useful. The only available measure of glycemia for comparison was a single fasting glucose level, and the authors acknowledge that this gives an incomplete measure, particularly in people with relatively mild diabetes, whose mean HbA1c was 6.4%, with most having levels of 7.5% or lower. In patients of this sort, postprandial glucose levels may better explain variations in mean HbA1c. Recognizing that the dataset may be limited, Jung et al. nevertheless give an intriguingly negative answer to the first question, of the reliability of HbA1c with kidney disease. Using Deming regression analysis, Jung et al. showed that the correlation between HbA1c and fasting glucose weakens as renal function worsens, and, moreover, that this appears particularly to be the case in people with anemia (hemoglobin men and women, respectively), confirming earlier observations. Among those diabetic people with neither anemia nor CKD, the correlation coefficient between HbA1c and fasting glucose was r = 0.70, compared with r = 0.35 among those with both anemia and very severe CKD (estimated glomerular filtration rate [eGFR] perform SMBG to more adequately interpret HbA1c results. © 2017 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.

  11. Effects of α-Thalassemia on HbA1c Measurement.

    Science.gov (United States)

    Xu, Anping; Ji, Ling; Chen, Weidong; Xia, Yong; Zhou, Yu

    2016-11-01

    α-Thalassemia is a benign condition that is often present in patients with diabetes mellitus. Here, we evaluated the effects of different genotypes α-thalassemia on HbA 1c measurement. A total of 189 samples from nondiabetic patients were analyzed. HbA 1c analysis was performed by ion-exchange high-performance liquid chromatography, boronate affinity HPLC, immunoassay, and capillary electrophoresis. Fasting glucose, fructosamin, and HbA 2 were also performed. All samples were confirmed by genotyping for thalassemia. In patients with two or three functional α-genes, HbA 1c values were not significantly different from those of controls (P > 0.05); however, in individuals with α-thalassemia with one functional α-gene (i.e., HbH disease), HbA 1c levels were significantly different from those of controls (P 0.05). In this study, HbA 1c values in samples from individuals with two or three functional α-genes basically reflected the normal mean blood glucose level, while those in samples from individuals with one functional α-gene did not. © 2016 Wiley Periodicals, Inc.

  12. RhHB1 mediates the antagonism of gibberellins to ABA and ethylene during rose (Rosa hybrida) petal senescence.

    Science.gov (United States)

    Lü, Peitao; Zhang, Changqing; Liu, Jitao; Liu, Xiaowei; Jiang, Guimei; Jiang, Xinqiang; Khan, Muhammad Ali; Wang, Liangsheng; Hong, Bo; Gao, Junping

    2014-05-01

    Rose (Rosa hybrida) is one of the most important ornamental plants worldwide; however, senescence of its petals terminates the ornamental value of the flower, resulting in major economic loss. It is known that the hormones abscisic acid (ABA) and ethylene promote petal senescence, while gibberellins (GAs) delay the process. However, the molecular mechanisms underlying the antagonistic effects amongst plant hormones during petal senescence are still unclear. Here we isolated RhHB1, a homeodomain-leucine zipper I transcription factor gene, from rose flowers. Quantitative RT-PCR and GUS reporter analyses showed that RhHB1 was strongly expressed in senescing petals, and its expression was induced by ABA or ethylene in petals. ABA or ethylene treatment clearly accelerated rose petal senescence, while application of the gibberellin GA3 delayed the process. However, silencing of RhHB1 delayed the ABA- or ethylene-mediated senescence, and resulted in higher petal anthocyanin levels and lower expression of RhSAG12. Moreover, treatment with paclobutrazol, an inhibitor of GA biosynthesis, repressed these delays. In addition, silencing of RhHB1 blocked the ABA- or ethylene-induced reduction in expression of the GA20 oxidase encoded by RhGA20ox1, a gene in the GA biosynthetic pathway. Furthermore, RhHB1 directly binds to the RhGA20ox1 promoter, and silencing of RhGA20ox1 promoted petal senescence. Eight senescence-related genes showed substantial differences in expression in petals after treatment with GA3 or paclobutrazol. These results suggest that RhHB1 mediates the antagonistic effect of GAs on ABA and ethylene during rose petal senescence, and that the promotion of petal senescence by ABA or ethylene operates through an RhHB1-RhGA20ox1 regulatory checkpoint. © 2014 The Authors The Plant Journal © 2014 John Wiley & Sons Ltd.

  13. Structured education using Dose Adjustment for Normal Eating (DAFNE) reduces long-term HbA1c and HbA1c variability.

    Science.gov (United States)

    Walker, G S; Chen, J Y; Hopkinson, H; Sainsbury, C A R; Jones, G C

    2018-06-01

    Previous evidence has demonstrated that participation in the Dose Adjustment for Normal Eating (DAFNE) education programme can reduce HbA 1c and severe hypoglycaemia in people with Type 1 diabetes. In a number of studies, increased HbA 1c variability has been associated with higher diabetic morbidity and mortality. No studies have examined the impact of structured education on HbA 1c variability in Type 1 diabetes. People with Type 1 diabetes who had attended DAFNE were identified for inclusion from the Scottish Care Information-Diabetes dataset. HbA 1c median and variability, expressed as coefficient of variation (CV) before and after DAFNE was calculated. Some 1061 individuals participated in DAFNE education and 687 met the inclusion criteria. A significant median reduction in HbA 1c [-3.5 mmol/mol (-0.3%)] was seen at 12 months with a significant reduction [-1.5 mmol/mol (-0.1%)] still seen at 60 months of follow-up. HbA 1c variability as measured by CV was significantly lower during the post-DAFNE period: 0.08 (IQR 0.05-0.12) reduced to 0.07 (IQR 0.05-0.10); P = 0.002. The data confirm that DAFNE participation improves glycaemic control in Type 1 diabetes with benefits being sustained for 5 years. This study is the first to demonstrate reduced HbA 1c variability after completion of structured education. This is new evidence of the beneficial impact of DAFNE on glycaemic profile. © 2018 Diabetes UK.

  14. Molecular Mechanism of AHSP-Mediated Stabilization of Alpha-Hemoglobin

    Energy Technology Data Exchange (ETDEWEB)

    Feng,L.; Gell, D.; Zhou, S.; Gu, L.; Kong, Y.; Li, J.; Hu, M.; Yan, N.; Lee, C.; et al.

    2005-01-01

    Hemoglobin A (HbA), the oxygen delivery system in humans, comprises two alpha and two beta subunits. Free alpha-hemoglobin (alphaHb) is unstable, and its precipitation contributes to the pathophysiology of beta thalassemia. In erythrocytes, the alpha-hemoglobin stabilizing protein (AHSP) binds alphaHb and inhibits its precipitation. The crystal structure of AHSP bound to Fe(II)-alphaHb reveals that AHSP specifically recognizes the G and H helices of alphaHb through a hydrophobic interface that largely recapitulates the alpha1-beta1 interface of hemoglobin. The AHSP-alphaHb interactions are extensive but suboptimal, explaining why beta-hemoglobin can competitively displace AHSP to form HbA. Remarkably, the Fe(II)-heme group in AHSP bound alphaHb is coordinated by the distal but not the proximal histidine. Importantly, binding to AHSP facilitates the conversion of oxy-alphaHb to a deoxygenated, oxidized [Fe(III)], nonreactive form in which all six coordinate positions are occupied. These observations reveal the molecular mechanisms by which AHSP stabilizes free alphaHb.

  15. Complex Interaction of Hb Q-Thailand (HBA1: c.223G>C) with β-Thalassemia/Hb E (HBB: c.79G>A) Disease.

    Science.gov (United States)

    Panyasai, Sitthichai; Satthakarn, Surada; Pornprasert, Sakorn

    2018-01-01

    Hb Q-Thailand [α74(EF3)Asp→His (α1), GAC>CAC, HBA1: c.223G>C] is an abnormal hemoglobin (Hb) frequently found in Thailand and Southeast Asian countries. The association of the α Q-Thailand allele with other globin gene disorders has important implications in diagnosis. Here, we report how to diagnose the coinheritance of Hb Q-Thailand with β-thalassemia (β-thal)/Hb E disease in four Thai samples from high performance liquid chromatography (HPLC) and capillary electrophoresis (CE) testing results. Understanding of the HPLC chromatogram and CE electropherogram patterns of this complex mutation is important for interpretation of testing results and providing genetic counseling.

  16. The heparin-binding domain of HB-EGF mediates localization to sites of cell-cell contact and prevents HB-EGF proteolytic release

    Energy Technology Data Exchange (ETDEWEB)

    Prince, Robin N.; Schreiter, Eric R.; Zou, Peng; Wiley, H. S.; Ting, Alice Y.; Lee, Richard T.; Lauffenburger, Douglas A.

    2010-07-01

    Heparin-binding EGF-like growth factor (HB-EGF) is a ligand for EGF receptor (EGFR) and possesses the ability to signal in juxtacrine, autocrine and/or paracrine mode, with these alternatives being governed by the degree of proteolytic release of the ligand. Although the spatial range of diffusion of released HB-EGF is restricted by binding heparan-sulfate proteoglycans (HSPGs) in the extracellular matrix and/or cellular glycocalyx, ascertaining mechanisms governing non-released HB-EGF localization is also important for understanding its effects. We have employed a new method for independently tracking the localization of the extracellular EGFlike domain of HB-EGF and the cytoplasmic C-terminus. A striking observation was the absence of the HB-EGF transmembrane proform from the leading edge of COS-7 cells in a wound-closure assay; instead, this protein localized in regions of cell-cell contact. A battery of detailed experiments found that this localization derives from a trans interaction between extracellular HSPGs and the HBEGF heparin-binding domain, and that disruption of this interaction leads to increased release of soluble ligand and a switch in cell phenotype from juxtacrine-induced growth inhibition to autocrine-induced proliferation. Our results indicate that extracellular HSPGs serve to sequester the transmembrane pro-form of HB-EGF at the point of cell-cell contact, and that this plays a role in governing the balance between juxtacrine versus autocrine and paracrine signaling.

  17. The Hb E (HBB: c.79G>A), Mean Corpuscular Volume, Mean Corpuscular Hemoglobin Cutoff Points in Double Heterozygous Hb E/- -SEA α-Thalassemia-1 Carriers are Dependent on Hemoglobin Levels.

    Science.gov (United States)

    Leckngam, Prapapun; Limweeraprajak, Ektong; Kiewkarnkha, Tiemjan; Tatu, Thanusak

    2017-01-01

    Identifying double heterozygosities in Hb E (HBB: c.79 G>A)/- - SEA (Southeast Asian) (α-thalassemia-1) (α-thal-1) in patients first diagnosed as carrying Hb E is important in thalassemia control. Low Hb E, mean corpuscular volume (MCV) and mean corpuscular hemoglobin (Hb) (MCH) levels have been observed in this double heterozygosity. However, the cutoff points of these parameters have never been systematically established. Here, we analyzed Hb E and red blood cell (RBC) parameters in 372 Hb E patients grouped by Hb levels, by the status of - - SEA and -α 3.7 (α-thal-2; rightward) deletions, to establish the cutoff points. Then, the established cutoff points were evaluated in 184 Hb E patients. It was found that the cutoff points of Hb E, MCV, MCH were significantly dependent on the Hb levels. In the group having Hb levels Hb E, MCV and MCH were 21.2%, 64.9 fL and 21.0 pg, respectively, and were 25.6%, 72.8 fL and 23.9 pg, respectively, in the group having Hb levels 10.0-11.9 g/dL. Finally, in the group having Hb levels ≥12.0 g/dL, the cutoff points of Hb E, MCV and MCH were 27.1%, 76.7 fL and 25.3 pg, respectively. Thus, to screen for the double heterozygous Hb E/- - SEA anomaly in patients initially diagnosed as carrying Hb E, the Hb levels must be taken into account in choosing the suitable cutoff points of these three parameters.

  18. Is insulin the preferred treatment for HbA1c >9%?

    Science.gov (United States)

    Bloomgarden, Zachary

    2017-09-01

    The algorithms and guidelines of the American Association of Clinical Endocrinologists and the American Diabetes Association recommend that insulin administration be strongly considered for people with type 2 diabetes (T2D) with HbA1c levels exceeding 9.0% and 10%, respectively. Although the caveat is given in both sets of recommendations that this is particularly appropriate when patients are "symptomatic," referring to urinary frequency with increased thirst and appetite, weight loss, and ketosis, the clinical definition of such presentations may be ill-defined, and it is noteworthy that both documents consider insulin to offer particular benefit under such circumstances. However, with multiple options for glycemic treatment, it is of interest to reconsider this argument for insulin use. It should be recalled that in the UK Prospective Diabetes Study, diet alone was associated with a reduction in HbA1c from 9% to 7%. Drug-naïve people with T2D do often show surprisingly strong reductions in HbA1c with metformin-based dual-agent oral treatment approaches; a recent report showed that even with baseline HbA1c >11%, the combination of metformin with a sulfonylurea, pioglitazone, or sitagliptin was associated with reduction in HbA1c from 11.6% to 6.0%. A 32-week study of the combination of rosiglitazone with metformin in patients with mean baseline HbA1c 8.9% showed a mean HbA1c reduction of 2.3%, and an open-label cohort with baseline HbA1c 11.8% had a reduction in HbA1c to 7.8%. With metformin plus sitagliptin, a mean placebo-adjusted HbA1c reduction of 2.1% from a baseline of 8.8% was reported, with those patients with baseline HbA1c >9% having a 2.6% reduction in HbA1c, and an open-label cohort with baseline HbA1c 11.2% having a 2.9% reduction in HbA1c. Similar 2% HbA1c reductions from baseline levels of 9.1% were seen with metformin in initial combination with the sodium-glucose cotransporter 2 (SGLT2) inhibitor dapagliflozin. Although such dual oral agent

  19. Formation of hemoglobin (Hb)-octadecylamine (ODA) Langmuir-Blodgett (LB) film by spreading Hb solution directly onto subphase covered with a layer of ODA and its electrochemical property

    International Nuclear Information System (INIS)

    Yin Fan; Shin, Hoon-Kyu; Kwon, Young-Soo

    2006-01-01

    The formation of hemoglobin (Hb)-octadecylamine (ODA) Langmuir-Blotgett (LB) film by spreading Hb solution directly onto subphase covered with a layer of ODA and its electrochemical properties were studied in this paper. This method ensured better electrode activity because almost no protein was adsorbed onto electrode surface before depositing Hb-ODA monolayer onto electrode surface. The optimum equilibrium time of Hb interacted with ODA layer, the optimum protein amount spread onto subphase's interface and the optimum ionic strength and pH of subphase were obtained from the experimental results. The compressibility analyses of Hb-ODA films showed that the surface pressure of this film from liquid-expanded to liquid-condensed state ranged between 16 and 40 mN/m. Direct electron transfer of Hb immobilized on gold electrode by LB technique was observed by cyclic voltammetry. Results showed that Hb molecules still kept their electrochemical activity. The electrode with Hb-ODA LB film displayed the fastest electron transfer rate when the film transferred under the surface pressure of 35 mN/m

  20. Formation of hemoglobin (Hb)-octadecylamine (ODA) Langmuir-Blodgett (LB) film by spreading Hb solution directly onto subphase covered with a layer of ODA and its electrochemical property

    Energy Technology Data Exchange (ETDEWEB)

    Yin Fan [Department of Electrical Engineering, Dong-A University, Busan 604-714 (Korea, Republic of); Department of Chemistry, Changshu Institute of Technology, Changshu, 215500 (China); Shin, Hoon-Kyu [Department of Electrical Engineering, Dong-A University, Busan 604-714 (Korea, Republic of); Kwon, Young-Soo [Department of Electrical Engineering, Dong-A University, Busan 604-714 (Korea, Republic of)]. E-mail: yskwon@daunet.donga.ac.kr

    2006-03-21

    The formation of hemoglobin (Hb)-octadecylamine (ODA) Langmuir-Blotgett (LB) film by spreading Hb solution directly onto subphase covered with a layer of ODA and its electrochemical properties were studied in this paper. This method ensured better electrode activity because almost no protein was adsorbed onto electrode surface before depositing Hb-ODA monolayer onto electrode surface. The optimum equilibrium time of Hb interacted with ODA layer, the optimum protein amount spread onto subphase's interface and the optimum ionic strength and pH of subphase were obtained from the experimental results. The compressibility analyses of Hb-ODA films showed that the surface pressure of this film from liquid-expanded to liquid-condensed state ranged between 16 and 40 mN/m. Direct electron transfer of Hb immobilized on gold electrode by LB technique was observed by cyclic voltammetry. Results showed that Hb molecules still kept their electrochemical activity. The electrode with Hb-ODA LB film displayed the fastest electron transfer rate when the film transferred under the surface pressure of 35 mN/m.

  1. A Mosaic Expression of a Hb J-Amiens (HBB: c.54G > T; p.Lys18Asn) and its Interference with Hb A1c Analysis.

    Science.gov (United States)

    Schiemsky, Toon; Van Hoovels, Lieve; Desmet, Koen J O; Phylipsen, Marion; Harteveld, Cornelis L; Kieffer, Davy M J

    2015-01-01

    We report the case of a 56-year-old Caucasian woman in whom hemoglobinopathy screening was triggered following an aberrant Hb A1c analysis. Preliminary diagnosis of the hemoglobin (Hb) variant was obtained through cation exchange high performance liquid chromatography (HPLC) and gel electrophoresis. DNA analysis confirmed the presence of Hb J-Amiens [β17(A14)Lys→Asn; HBB: c.[54G > C or 54G > T)]. However, an unbalanced ratio between wild type and mutant signal after direct sequencing and a lower than expected percentage of this Hb variant led to the suggestion of a mosaic expression. Furthermore, different methods [capillary zone electrophoresis (CZE), cation exchange HPLC and boronate affinity] were tested to study the possible interference of this variant with Hb A1c measurements. These investigations showed a clinically relevant difference between the methods tested. Hb A1c analysis may lead to the discovery of new Hb variants or mosaicism for previously described Hb variants. This may have genetic consequences for the offspring of carriers and brings about the question of partner testing.

  2. Dificuldades na identificação laboratorial da talassemia alfa Difficulty on laboratory identification of alpha thalassemia

    Directory of Open Access Journals (Sweden)

    Karlla Greick Batista Dias-Penna

    2010-04-01

    Full Text Available Introdução: Talassemia alfa é uma síndrome associada à redução da síntese de cadeias de globina do tipo alfa. A gravidade das manifestações clínicas está relacionada com a quantidade de globinas produzida e a estabilidade das cadeias beta presentes em excesso. A talassemia alfa mínima resulta da deleção de apenas um dos quatro genes a (-α/αα. Clinicamente apresenta anemia leve com microcitose ou ausência de anemia, sendo o diagnóstico realizado por meio de visualização da hemoglobina (Hb H por eletroforese alcalina em acetato de celulose ou por identificação de inclusões celulares de Hb H coradas pelo azul de crezil brilhante. Objetivo: Avaliar portadores de talassemia alfa e seus respectivos progenitores, correlacionando perfil hematológico e presença de Hb H, utilizando procedimentos laboratoriais clássicos em três diferentes amostragens. Discussão e conclusão: Os dados obtidos mostram que a presença de Hb H, indicativo de talassemia alfa, pode não ser confirmada em uma análise posterior. Entre os fatores que podem influenciar no não aparecimento de Hb H em pessoa comprovadamente com talassemia alfa está a deficiência de ferro. A talassemia alfa está associada a defeitos envolvendo os genes codificadores da cadeia alfa, mas também pode estar relacionada com desbalanciamento temporário na expressão dos genes globina, diminuição de alfa ou aumento de beta, o que poderia explicar o aparecimento de tetrâmeros de cadeia beta (Hb H, sugerindo diagnóstico de talassemia alfa mínima.Introduction: Alpha thalassemia is a syndrome with associated with the reduction of alpha globin chain synthesis. The severity of clinical manifestations is related to the amount of globins produced and the stability of beta chains that are present in excess. Alpha thalassemia minor is caused by the deletion of one of the four genes a (-α/αα. Clinically, it presents mild anemia with microcytosis or absence of anemia. The

  3. Use of Fructosyl Peptide Oxidase for HbA1c Assay

    Science.gov (United States)

    Yonehara, Satoshi; Inamura, Norio; Fukuda, Miho; Sugiyama, Koji

    2015-01-01

    ARKRAY, Inc developed the world’s first automatic glycohemoglobin analyzer based on HPLC (1981). After that, ARKRAY developed enzymatic HbA1c assay “CinQ HbA1c” with the spread and diversification of HbA1c measurement (2007). CinQ HbA1c is the kit of Clinical Chemistry Analyzer, which uses fructosyl peptide oxidase (FPOX) for a measurement reaction. This report mainly indicates the developmental background, measurement principle, and future of the enzymatic method HbA1c reagent. PMID:25633966

  4. The Long and Winding Road to Optimal HbA1c Measurement

    Science.gov (United States)

    Little, Randie R.; Rohlfing, Curt

    2016-01-01

    The importance of hemoglobin A1c (HbA1c) as an indicator of mean glycemia and risks for complications in patients with diabetes mellitus was established by the results of long-term clinical trials, most notably the Diabetes Control and Complications Trial (DCCT) and United Kingdom Prospective Diabetes Study (UKPDS), published in 1993 and 1998 respectively. However, clinical application of recommended HbA1c targets that were based on these studies was difficult due to lack of comparability of HbA1c results among assay methods and laboratories. Thus, the National Glycohemoglobin Standardization Program (NGSP) was initiated in 1996 with the goal of standardizing HbA1c results to those of the DCCT/UKPDS. HbA1c standardization efforts have been highly successful; however, a number of issues have emerged on the “long and winding road” to better HbA1c, including the development of a higher-order HbA1c reference method by the International Federation of Clinical Chemistry (IFCC), recommendations to use HbA1c to diagnose as well as monitor diabetes, and point-of-care (POC) HbA1c testing. Here, we review the past, present and future of HbA1c standardization and describe the current status of HbA1c testing, including limitations that healthcare providers need to be aware of when interpreting HbA1c results. PMID:23318564

  5. Bridging Theory and Experiment to Address Structural Properties of Truncated Haemoglobins: Insights from Thermobifida fusca HbO.

    Science.gov (United States)

    Howes, Barry D; Boechi, Leonardo; Boffi, Alberto; Estrin, Dario E; Smulevich, Giulietta

    2015-01-01

    In this chapter, we will discuss the paradigmatic case of Thermobifida fusca (Tf-trHb) HbO in its ferrous and ferric states and its behaviour towards a battery of possible ligands. This choice was dictated by the fact that it has been one of the most extensively studied truncated haemoglobins, both in terms of spectroscopic and molecular dynamics studies. Tf-trHb typifies the structural properties of group II trHbs, as the active site is characterized by a highly polar distal environment in which TrpG8, TyrCD1, and TyrB10 provide three potential H-bond donors in the distal cavity capable of stabilizing the incoming ligands. The role of these residues in key topological positions, and their interplay with the iron-bound ligands, has been addressed in studies carried out on the CO, F(-), OH(-), CN(-), and HS(-) adducts formed with the wild-type protein and a combinatorial set of mutants, in which the distal polar residues, TrpG8, TyrCD1, and TyrB10, have been singly, doubly, or triply replaced by a Phe residue. In this context, such a complete analysis provides an excellent benchmark for the investigation of the relationship between protein structure and function, allowing one to translate physicochemical properties of the active site into the observed functional behaviour. Tf-trHb will be compared with other members of the group II trHbs and, more generally, with members of the other trHb subgroups. © 2015 Elsevier Ltd. All rights reserved.

  6. Recent Progress in Electrochemical HbA1c Sensors: A Review

    Directory of Open Access Journals (Sweden)

    Baozhen Wang

    2015-03-01

    Full Text Available This article reviews recent progress made in the development of electrochemical glycated hemoglobin (HbA1c sensors for the diagnosis and management of diabetes mellitus. Electrochemical HbA1c sensors are divided into two categories based on the detection protocol of the sensors. The first type of sensor directly detects HbA1c by binding HbA1c on the surface of an electrode through bio-affinity of antibody and boronic acids, followed by an appropriate mode of signal transduction. In the second type of sensor, HbA1c is indirectly determined by detecting a digestion product of HbA1c, fructosyl valine (FV. Thus, the former sensors rely on the selective binding of HbA1c to the surface of the electrodes followed by electrochemical signaling in amperometric, voltammetric, impedometric, or potentiometric mode. Redox active markers, such as ferrocene derivatives and ferricyanide/ferrocyanide ions, are often used for electrochemical signaling. For the latter sensors, HbA1c must be digested in advance by proteolytic enzymes to produce the FV fragment. FV is electrochemically detected through catalytic oxidation by fructosyl amine oxidase or by selective binding to imprinted polymers. The performance characteristics of HbA1c sensors are discussed in relation to their use in the diagnosis and control of diabetic mellitus.

  7. Transcriptional regulation of Hb-α and Hb-β through nuclear factor E2-related factor-2 (Nrf2) activation in human vaginal cells: A novel mechanism of cellular adaptability to oxidative stress.

    Science.gov (United States)

    Saha, Debarchana; Koli, Swanand; Reddy, Kudumula Venkata Rami

    2017-06-01

    Hemoglobin (Hb), a major protein involved in transport of oxygen (O 2 ), is expressed by erythroid lineages. Until recently, it was not known whether non-erythroid cells express Hb. The objective was to evaluate the expression and functional significance of Hb-α and Hb-β in human primary vaginal epithelial cells (hPVECs) and decipher downstream signaling. RT-PCR, qRT-PCR, flow cytometry, Western blot, immunofluorescence were used to evaluate the expression of Hb-α, Hb-β, and nuclear factor E2-related factor-2(Nrf2) after hydrogen peroxide (H 2 O 2 ) induction. Electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP) assay were used to determine the binding efficiency of Nrf2 on the Hb-α promoter. Stimulation of hPVECs and human vaginal epithelial cell line, VK2/E6E7 with H 2 O 2 augmented the expression of Hb-α, Hb-β, Nrf2, heme oxygenase-1 (HO-1), and reactive oxygen species (ROS). Treatment of these cells with Nrf2 inhibitor, trigonelline (Trig) inhibited Hb-α and Hb-β expressions. Hb-α and Hb-β overexpression downregulated H 2 O 2 -induced ROS. The presence of Nrf2 binding domain was demonstrated within Hb-α promoter. The results revealed for the first time that Hb-α and Hb-β were induced by oxidative stress through the activation of Nrf2. Overexpression of Hb-α and Hb-β ameliorated H 2 O 2 -induced oxidative stress, indicating one of the possible mechanism(s) to protect hPVECS from oxidative stress. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  8. Ferulic acid modification enhances the anti-oxidation activity of natural Hb in vitro.

    Science.gov (United States)

    Qi, Donglai; Li, Qian; Chen, Chen; Wang, Xiang

    2018-03-13

    During the development of artificial red blood cell (RBC) substitutes, oxidation side reaction is one of the major factors that hinder the application of haemoglobin (Hb)-based oxygen carriers (HBOCs). In order to avoid oxidation toxicity, we designed and prepared natural Hb conjugated with ferulic acid (FA) via simple chemical modification. In addition, the thiol groups on Hb surface were increased via the reaction of Hb with 2-iminothiolane (2-IT) and then modified with FA for the study of anti-oxidant ability. It was showed that Hb modified with FA (FA-Hb) had similar oxygen-binding capacity to natural Hb. Moreover, the anti-oxidant ability of FA-Hb in vitro in different systems was superior to natural Hb and in proportion to the degree of modification of FA. The results indicate that FA-Hb might have the potential to serve as a novel oxygen carrier with the capacity to reduce oxidative side reaction.

  9. Hb TAYBE: clinical and morphological findings IN 43 patients.

    Science.gov (United States)

    Koren, Ariel; Levin, Carina; Zalman, Luci; Palmor, Haya; Filon, Dvora; Chubar, Evgeny; Resnitzky, Peretz; Bennett, Michael

    2016-08-01

    Hereditary sequence variants in globin genes are usually silent and are rarer in α-globin chains than β-globin chains. Some may lead to an unstable protein with a hemolytic or thalassemic phenotype. Hb Taybe is an unstable α-chain hemoglobin variant caused by the deletion of a threonine residue at codon 38 or 39 of the α1 globin gene. This deletion results in a structural abnormality that affects the α1 β2 contact and the α1 β1 interface, producing a highly unstable Hb. We describe the clinical, laboratory, and morphological characteristics of 43 patients with Hb Taybe, sixteen of whom are heterozygous, eight are homozygous, and nineteen are double heterozygous for Hb Taybe and other α-gene mutations or deletions. The clinical presentation is very variable from a mild hemolytic anemia to the need for red cell transfusion. Morphological characteristics include erythroid hyperplasia, defective hemoglobin production, and dyserythropoietic features. On electron microscopy dyserythropoiesis and cytoplasmic precipitation of globin compatible optical dense material is seen. This is the largest report of Hb Taybe patients. Previous reported cohorts are not related to these cases. We conclude that patients carrying Hb Taybe have a unique hematological and clinical phenotype distinct from other hemoglobinopathies and from congenital dyserythropoietic anemia. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  10. Molecular characterization of ruminal bacterial diversity in vitro = Caracterização molecular da diversidade bacteriana ruminal in vitro

    Directory of Open Access Journals (Sweden)

    Humberto Maciel França Madeira

    2008-04-01

    Full Text Available PCR analysis is a sensitive and specific tool to detect and monitormicroorganisms in complex environmental samples. The amplification of 16S ribosomal DNA sequences followed by gel electrophoresis under denaturing gradient (DGGE has been a powerful technique to genetically evaluate microbial ecosystems. Changes in rumenmicrobial populations were investigated in vitro using a basal diet with different lipid sources. PCRs were performed with two different sets of primers in order to amplify 16S rRNA sequences, and the amplified fragments were submitted to DGGE analysis. The findings presented in this study show that distinct microbial communities were present in each treatment. The presence of soybean oil seems to maximize growth of bacterial population, whereas fish oil appears to reduce growth. We demonstrated the successful application of molecular ecological techniques to analyze the structure and composition of bacterial communities in rumen ecosystems.A análise por PCR fornece um meio sensível e específico para detectar e monitorar microrganismos em amostras ambientais complexas. Desde sua aplicação inicial, o DNA ribossomal 16S (rRNA em eletroforese com gel com gradiente desnaturante (DGGE, tem sido uma técnica atrativa para a ecologia molecular microbiana. Foram investigadas mudanças na população microbiana no rúmen, a partir de alterações da dieta com tratamentos in vitro de diferentes fontes de lipídeos. ODGGE foi testado com dois pares de primers para o rRNA 16S. O uso do fragmento de 200 pb gerou um perfil de bandas mais discriminatório, mostrando que diferentes comunidades microbianas estavam presentes entre os tratamentos in vitro analisados. A presença de óleo de sojapotencializou o crescimento da população bacteriana, enquanto que óleo de peixe parece ter reduzido esse crescimento. Foi possível demonstrar o sucesso da aplicação de técnicas moleculares para analisar a estrutura e a composição de comunidades

  11. Thrombosis in Hb Taybe [codons 38/39 (-ACC) (α1)

    DEFF Research Database (Denmark)

    Juul, Maja Bech; Vestergaard, Hanne; Petersen, Jesper

    2012-01-01

    Hb Taybe is a highly unstable hemoglobin (Hb) variant caused by a 3 bp deletion at codons 38/39 (-ACC) on the α1-globin gene. We report for the first time, a patient with a compound heterozygosity for Hb Taybe and a 5 bp deletion at the splice donor site of IVS-I on the α2-globin gene and ischemic...

  12. Mechanosensitive promoter region in the human HB-GAM gene

    DEFF Research Database (Denmark)

    Liedert, Astrid; Kassem, Moustapha; Claes, Lutz

    2009-01-01

    Mechanical loading is essential for maintaining bone mass in the adult skeleton. However, the underlying process of the transfer of the physical stimulus into a biochemical response, which is termed mechanotransduction is poorly understood. Mechanotransduction results in the modulation of gene...... cells. Analysis of the human HB-GAM gene upstream regulatory region with luciferase reporter gene assays revealed that the upregulation of HB-GAM expression occurred at the transcriptional level and was mainly dependent on the HB-GAM promoter region most upstream containing three potential AP-1 binding...

  13. Excess HB-EGF, which promotes VEGF signaling, leads to hydrocephalus

    Science.gov (United States)

    Shim, Joon W.; Sandlund, Johanna; Hameed, Mustafa Q.; Blazer-Yost, Bonnie; Zhou, Feng C.; Klagsbrun, Michael; Madsen, Joseph R.

    2016-01-01

    Heparin binding epidermal growth factor-like growth factor (HB-EGF) is an angiogenic factor mediating radial migration of the developing forebrain, while vascular endothelial growth factor (VEGF) is known to influence rostral migratory stream in rodents. Cell migratory defects have been identified in animal models of hydrocephalus; however, the relationship between HB-EGF and hydrocephalus is unclear. We show that mice overexpressing human HB-EGF with β-galactosidase reporter exhibit an elevated VEGF, localization of β-galactosidase outside the subventricular zone (SVZ), subarachnoid hemorrhage, and ventriculomegaly. In Wistar polycystic kidney rats with hydrocephalus, alteration of migratory trajectory is detected. Furthermore, VEGF infusions into the rats result in ventriculomegaly with an increase of SVZ neuroblast in rostral migratory stream, whereas VEGF ligand inhibition prevents it. Our results support the idea that excess HB-EGF leads to a significant elevation of VEGF and ventricular dilatation. These data suggest a potential pathophysiological mechanism that elevated HB-EGF can elicit VEGF induction and hydrocephalus. PMID:27243144

  14. Predictors of HbA1c levels in patients initiating metformin.

    Science.gov (United States)

    Martono, Doti P; Hak, Eelko; Lambers Heerspink, Hiddo; Wilffert, Bob; Denig, Petra

    2016-12-01

    The aim was to assess demographic and clinical factors as predictors of short (6 months) and long term (18 months) HbA1c levels in diabetes patients initiating metformin treatment. We conducted a cohort study including type 2 diabetes patients who received their first metformin prescription between 2007 and 2013 in the Groningen Initiative to Analyze Type 2 Diabetes Treatment (GIANTT) database. The primary outcome was HbA1c level at follow-up adjusted for baseline HbA1c; the secondary outcome was failing to achieve the target HbA1c level of 53 mmol/mol. Associations were analyzed by linear and logistic regression. Multiple imputation was used for missing data. Additional analyses stratified by dose and adherence level were conducted. The cohort included 6050 patients initiating metformin. Baseline HbA1c at target consistently predicted better HbA1c outcomes. Longer diabetes duration and lower total cholesterol level at baseline were predictors for higher HbA1c levels at 6 months. At 18 months, cholesterol level was not a predictor. Longer diabetes duration was also associated with not achieving the target HbA1c at follow-up. The association for longer diabetes duration was especially seen in patients starting on low dose treatment. No consistent associations were found for comorbidity and comedication. Diabetes duration was a relevant predictor of HbA1c levels after 6 and 18 months of follow-up in patients initiating metformin treatment. Given the study design, no causal inference can be made. Our study suggests that prompt treatment intensification may be needed in patients who have a longer diabetes duration at treatment initiation.

  15. Effect of once-weekly dulaglutide on glycated haemoglobin (HbA1c) and fasting blood glucose in patient subpopulations by gender, duration of diabetes and baseline HbA1c.

    Science.gov (United States)

    Gallwitz, Baptist; Dagogo-Jack, Samuel; Thieu, Vivian; Garcia-Perez, Luis-Emilio; Pavo, Imre; Yu, Maria; Robertson, Kenneth E; Zhang, Nan; Giorgino, Francesco

    2018-02-01

    To evaluate the efficacy and safety of dulaglutide 1.5 and 0.75 mg in patients with type 2 diabetes by subgroups of gender, duration of diabetes and baseline glycated haemoglobin (HbA1c) in the dulaglutide clinical development programme (AWARD-1 to -6 and -8 clinical trials). Change in HbA1c was analysed by gender, duration of diabetes (baseline HbA1c (baseline in weight, hypoglycaemia and gastrointestinal adverse events were evaluated for individual trials. In the pooled analysis of patients treated with dulaglutide 1.5 mg at 6 months, the reductions in HbA1c from baseline were similar across gender (men: least squares [LS] mean -1.26% [95% confidence interval {CI} -1.36, -1.16]; women: LS mean -1.33% [95% CI -1.43, -1.24]) and among duration of diabetes subgroups (baseline HbA1c ≥8.5% had greater HbA1c reductions than patients with baseline HbA1c baseline HbA1c subgroups, respectively; women had a numerically greater weight loss or less weight gain than men with both dulaglutide doses. There was no clinically meaningful difference in hypoglycaemia trends by gender or duration of diabetes. Hypoglycaemia incidence and rate were generally lower in patients with baseline HbA1c ≥8.5% than in those with baseline HbA1c, with greater HbA1c and FBG reductions in patients with a higher baseline HbA1c. Dulaglutide was well tolerated, with a safety profile similar to other glucagon-like peptide-1 receptor agonists. © 2017 John Wiley & Sons Ltd.

  16. Modeling Single-Phase PV HB-ZVR Inverter Connected to Grid

    DEFF Research Database (Denmark)

    Guo, Yougui; Zeng, Ping; Zhu, Jieqiong

    2011-01-01

    PLECS is used to model the PV H-bridge zero voltage rectifier (HB-ZVR) inverter connected to grid and good results are obtained. First, several common topologies of PV inverters are introduced. Then the unipolar PWM control strategy is described for PV HB-ZVR inverter. Third, PLECS is briefly...... introduced. Fourth, the modeling of PV HB-ZVR inverter is presented with PLECS. Finally, a series of simulations are carried out. The simulation results tell us PLECS is very powerful tool to real power circuits and it is very easy to simulate LCL filter. They have also verified that the unipolar PWM control...... strategy is feasible to control the PV HB-ZVR inverter....

  17. Should Studies of Diabetes Treatment Stratification Correct for Baseline HbA1c?

    Science.gov (United States)

    Jones, Angus G.; Lonergan, Mike; Henley, William E.; Pearson, Ewan R.; Hattersley, Andrew T.; Shields, Beverley M.

    2016-01-01

    Aims Baseline HbA1c is a major predictor of response to glucose lowering therapy and therefore a potential confounder in studies aiming to identify other predictors. However, baseline adjustment may introduce error if the association between baseline HbA1c and response is substantially due to measurement error and regression to the mean. We aimed to determine whether studies of predictors of response should adjust for baseline HbA1c. Methods We assessed the relationship between baseline HbA1c and glycaemic response in 257 participants treated with GLP-1R agonists and assessed whether it reflected measurement error and regression to the mean using duplicate ‘pre-baseline’ HbA1c measurements not included in the response variable. In this cohort and an additional 2659 participants treated with sulfonylureas we assessed the relationship between covariates associated with baseline HbA1c and treatment response with and without baseline adjustment, and with a bias correction using pre-baseline HbA1c to adjust for the effects of error in baseline HbA1c. Results Baseline HbA1c was a major predictor of response (R2 = 0.19,β = -0.44,pHbA1c were associated with response, however these associations were weak or absent after adjustment for baseline HbA1c. Bias correction did not substantially alter associations. Conclusions Adjustment for the baseline HbA1c measurement is a simple and effective way to reduce bias in studies of predictors of response to glucose lowering therapy. PMID:27050911

  18. A patogênese genética e molecular da síndrome de Angelman

    Directory of Open Access Journals (Sweden)

    Angelica Francesca Maris

    2011-01-01

    Full Text Available Objetivo: Fornecer uma revisão atualizada em língua portuguesa sobre a síndrome de Angelman, com ênfase nos mecanismos genéticos e moleculares dessa patologia, uma causa de deficiência mental severa que em alguns casos pode apresentar recorrência familiar. Método: Foi feita uma revisão bibliográfica utilizando a base de dados do PubMed, tendo como critérios de busca o termo "Angelman syndrome" isoladamente e combinado com "UBE3A", "clinical", "genetics" e "molecular" no título dos artigos. Dentre esses, foram selecionados artigos de revisão e artigos originais sobre a fisiopatologia da síndrome, com ênfase nos últimos dez anos. Resultados: Utilizando-se "Angelman syndrome" na busca, apareceram cerca de 1.100 artigos, incluindo 240 de revisão. Nos últimos dez anos são mais de 600 artigos, aproximadamente 120 de revisão, 50% dos quais publicados nos últimos cinco anos. Na base de dados SciELO, são apenas nove artigos sobre a síndrome, dos quais três em português e nenhum artigo atual de revisão. Conclusão: Após ter sido uma das principais causas que atraíram atenção ao estudo e ao entendimento dos mecanismos do imprinting genômico, a síndrome de Angelman está agora se revelando como uma patologia das sinapses. Apesar de o entendimento da fisiopatologia molecular da síndrome de Angelman ainda estar longe de ser compreendida, seu estudo está fornecendo uma visão extraordinária sobre os mecanismos que regem a plasticidade sináptica, novamente atraindo a atenção de pesquisadores que trabalham na fronteira do conhecimento.

  19. Permanent LMN denervation of human skeletal muscle and recovery by h-b FES: management and monitoring

    Directory of Open Access Journals (Sweden)

    Helmut Kern

    2010-09-01

    Full Text Available Denervation of a defined skeletal muscle is due to lower motor neuron (LMN or peripheral nerve lesions that have major consequences on the muscle tissue. After early atrophy, the mid- and late-phases presents two very contrasting myofibers populations: beside those severely atrophic with internalized groups of myonuclei, large fast-type muscle fibers continue to be present 4 to 6 years after Spinal Cord Injury (SCI. Recent results of rat experiments provides the rational basis for understanding the residual functional characteristics of the long-term denervated muscle and the molecular explanation of its ability to respond to home-base functional electrical stimulation (h-b FES using custom-designed electrodes and stimulators. Further outcomes of the Vienna-Padova ten-year collaboration are: 1. a world-unique Myo- Bank of muscle biopsies and 2. improved imaging procedures (Color Computer Tomography (CT scan and Functional Echomyography, all demonstrating that h-b FES induces improvements in muscle contractility, tissue composition and mass, despite permanent LMN denervation. The benefits of h-b FES could be extended from patents suffering with complete Conus-Cauda Syndrome to the numerous patients with incomplete LMN denervation of skeletal muscles to determine whether h-b FES reduces secondary complications related to disuse and impaired blood perfusion (reduction in bone density, risk of bone fracture, decubitus ulcers, and pulmonary thromboembolism. We are confident that translation of the results of a clinical experiment, the EU Project RISE, to the larger cohort of incomplete LMN denervated muscles will provide the wanted results.

  20. ERGEBNISSE DER UNTERSUCHUNG VON HB-AL BEI 94 PATIENTEN MIT NIERENINSUFFIZIENZ

    Directory of Open Access Journals (Sweden)

    A

    1983-05-01

    Full Text Available We have qua nt i t a l ed Hb- Al ~n 125 patients . 74 pa t ient s had chronic Renal Failure . 20 of them had Diabetes wi th Renal Fai lure , 21 Diabetics and 10 patients were evaluat ed as control. We have divided the patients with Renal Failure i n 3 groups according to t heir serum c reatin i ne . Hb-Al in a ll groups "as not correlated wi th serum creat i ne. Hb-Al in Diabetic gr oup was highe r than Diabetic patients with Renal Failure . This group a lso had mor e HbA1 than t he gr oup with Renal ~ailure a nd no Diabetes ,and control group . , Hb-Al was correlated with Blood suger i n all pa t i e nt s s o we can u se"nal Failure the me a sureme nt of Hb-Al i n pati ents with Renunder Dial ys i s with gl ucose solution fo r evalua t i o n of sugar meta boli s m.  

  1. A importância da determinação da hemoglobina glicada no monitoramento das complicações crônicas do diabetes mellitus The importance of glycated hemoglobin determination in the management of chronic complications associated with diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Andreza Fabro de Bem

    2006-06-01

    Full Text Available O diabetes é uma situação clínica muito freqüente que envolve cerca de 7% da população mundial. Por essa razão muitos esforços têm sido empregados na implementação de métodos de monitoramento e no desenvolvimento de terapias efetivas para o seu controle. A hemoglobina glicada (HbA1c é o teste mais indicado na quantificação do risco de complicações crônicas em pacientes diabéticos. O Diabetes Control and Complications Trial (DCCT e o United Kingdom Prospective Diabetes Study (UKPDS concluíram que o risco de complicações em pacientes diabéticos é diretamente proporcional ao controle glicêmico, determinado através dos níveis de HbA1c. A medida exata e precisa da HbA1c é uma questão importante para os laboratórios clínicos, sendo que vários fatores podem afetar as determinações, levando a resultados equivocados. O objetivo deste estudo é demonstrar os diferentes métodos para a quantificação da HbA1c, bem como discutir os problemas mais freqüentes de padronização dessa determinação.Diabetes is a widespread disease, involving about 7% of the entire world population. For this reason, many efforts have been devoted to the wide application of valid monitoring procedures and to the development of effective therapeutic approaches. Glycated hemoglobin (HbA1c is the pre-eminent factor for quantifying the risk of chronic complications in patients with diabetes. The Diabetes Control and Complications Trial (DCCT and United Kingdom Prospective Diabetes Study (UKPDS, demonstrated conclusively that risks for complications in patients with diabetes are directly related to glycemic control, as measured by glycated hemoglobin (HbA1c. Accurate determination of HbA1c is an important issue for clinical laboratories and several factors may affect and lead to erroneous results. The main objective of this study is to show the different methods for glycated hemoglobin quantification and to discuss the most frequent problems of

  2. GENETIC FACTORS INFLUENCING HEMOGLOBIN F LEVEL IN β-THALASSEMIA/HB E DISEASE.

    Science.gov (United States)

    Ruangrai, Waraporn; Jindadamrongwech, Sumalee

    2016-01-01

    Genetic factors influencing Hb F content in adult red blood cells include β-thalassemia genotypes, co-inheritance of α-thalassemia traits and single nucleotide polymorphisms (SNPs). Genotyping of α- and β-thalassemia and five SNPs in β-globin gene cluster previously identified in genome-wide association studies as being markers of elevated Hb F in β-thalassemia were performed in 81 subjects diagnosed with β-thalassemia/Hb E. Hb F levels are higher (0.9-7.1 g/dl) in subjects (n = 57) with the severe compared to mild β-thalassemia (0.8-2.5 g/ dl) (n = 4) genotypes, and are similarly low (0.7-3.5 g/dl) in those (n = 15) with α-thalassemia co-inheritance. Hb F levels in non-thalassemia controls (n = 150) range from 0 to 0.15 g/dl. The presence of homozygous minor alleles of the 5 SNPs are significant indicators of β-thalassemia/Hb E individuals with high Hb F (> 4 g/dl), independent of their thalassemia genotypes. Given that re-activation of γ-globin genes leads to amelioration of β-thalassemia severity, understanding how genetic factors up-regulate Hb F production may lead to possible therapeutic interventions, genetically or pharmacologically, of this debilitating disease in the not too distant future.

  3. Relationship of HbA1c variability, absolute changes in HbA1c, and all-cause mortality in type 2 diabetes

    DEFF Research Database (Denmark)

    Skriver, Mette Vinther; Sandbæk, Annelli; Kristensen, Jette Kolding

    2015-01-01

    OBJECTIVE: We assessed the relationship of mortality with glycated hemoglobin (HbA1c) variability and with absolute change in HbA1c. DESIGN: A population-based prospective observational study with a median follow-up time of 6 years. METHODS: Based on a validated algorithm, 11 205 Danish individua...

  4. Avaliação da capacidade funcional para o exercício de crianças e adolescentes com doença falciforme pelo teste da caminhada de seis minutos

    Directory of Open Access Journals (Sweden)

    Sandro V. Hostyn

    2013-12-01

    Full Text Available OBJETIVO: avaliar a capacidade funcional pulmonar (CF para o exercício físico de crianças e adolescentes com doença falciforme (DF pelo teste da caminhada de seis minutos (TC6'. MÉTODOS: estudo transversal prospectivo avaliando a CF pelo TC6' de 46 pacientes com DF. Foram avaliados: frequência cardíaca (FC, frequência respiratória (FR, saturação de pulso de oxigênio (SpO2, pico de fluxo expiratório (PFE, pressão arterial (PA sistólica e diastólica, dispneia e cansaço em membros inferiores (escala de Borg modificada em repouso, ao término e 10 minutos após o TC6' e a distância percorrida. Análise estatística: test t-Student pareado, análise de variância e comparações múltiplas de Bonferroni, significância p < 0,05. RESULTADOS: dos 46 pacientes, a média ± dp da idade foi 9,15 ± 3,06 anos, hemoglobina basal 9,4 ± 1,67 g/dL e distância percorrida 480,89 ± 68,70 m. Diagnóstico da DF: Grupo 1- HbSS (n = 20/HbSβ0-talassemia (n = 3; e Grupo 2 - HbSC (n = 20/ HbSβ+-talassemia (n = 3. O Grupo 1 apresentou menor distância percorrida do que o Grupo 2 (459,39 ± 57,19 vs 502,39 ± 73,60m; p = 0,032. Não houve diferença estatística em relação ao PFE. A SpO2 em ar ambiente e a SpO2 com O2 (1 L/min após o teste foi maior no Grupo 2 (p < 0,001 e p = 0,002, respectivamente. A FR foi maior no Grupo 1 ao final do TC6' (p < 0,001. CONCLUSÃO: esta amostra apresentou CF para o exercício abaixo do predito para a faixa etária na literatura. Os pacientes com HbSS/Sβ0-talassemia apresentaram desempenho inferior na distância percorrida, FR e SpO2 após o TC6', comparativamente aos pacientes com HbSC/Sβ+-talassemia.

  5. Molecular analysis of abnormal hemoglobins in beta chain in Aegean region of Turkey and first reports of hemoglobin Andrew-Minneapolis and Hb Hinsdale from Turkey.

    Science.gov (United States)

    Aykut, Ayça; Onay, Hüseyin; Durmaz, Asude; Karaca, Emin; Vergin, Canan; Aydınok, Yeşim; Özkınay, Ferda

    2015-07-01

    The Agean is one of the regions in Turkey where thalassemias and abnormal hemoglobins (Hbs) are prevalent. Combined heterozygosity of thalassemia mutations with a variety of structural Hb variants lead to an extremely wide spectrum of clinical and hematological phenotypes which is of importance for prenatal diagnosis. One hundred and seventeen patients and carriers diagnosed by hemoglobin electrophoresis (HPLC), at risk for abnormal hemoglobinopathies were screened for mutational analysis of the beta-globin gene. The full coding the 5' UTR, and the 3' UTR sequences of beta-globin gene (GenBank accession no. U01317) were amplified and sequenced. In this study, a total of 118 (12.24%) structural Hb variant alleles were identified in 1341 mutated beta-chain alleles in Medical Genetics Department of Ege University between January 2006 and November 2013. Here, we report the mutation spectrum of abnormal Hbs associated with the beta-globin gene in Aegean region of Turkey. In the present study, the Hb Hinsdale and Hb Andrew-Minneapolis variants are demonstrated for the first time in the Turkish population.

  6. Influence of semisynthetic modification of the scaffold of a contact domain of HbS on polymerization: role of flexible surface topology in polymerization inhibition.

    Science.gov (United States)

    Sonati, Srinivasulu; Bhutoria, Savita; Prabhakaran, Muthuchidambaran; Acharya, Seetharama A

    2018-02-01

    A new variant of HbS, HbS-Einstein with a deletion of segment α 23-26 in the B-helix, has been assembled by semisynthetic approach. B-helix of the α chain of cis αβ-dimer of HbS plays dominant role in the quinary interactions of deoxy HbS dimer. This B-helix is the primary scaffold that provides the orientation for the side chains of contact residues of this intermolecular contact domain. The design of HbS-Einstein has been undertaken to map the influence of perturbation of molecular surface topology and the flexibility of surface residues in the polymerization. The internal deletion exerts a strong inhibitory influence on Val-6 (β)-dependent polymerization, comparable to single contact site mutations and not for complete neutralization of Val-6(β)-dependent polymerization. The scaffold modification in cis-dimer is inhibitory, and is without any effect when present on the trans dimer. The flexibility changes in the surface topology in the region of scaffold modification apparently counteracts the intrinsic polymerization potential of the molecule. The inhibition is close to that of Le Lamentin mutation [His-20 (α) → Gln] wherein a mutation engineered without much change in flexibility of the contact domain. Interestingly, the chimeric HbS with swine-human chimeric α chain with multiple non-conservative mutations completely inhibits the Val-6(β)-dependent polymerization. The deformabilities of surface topology of chimeric HbS are comparable to HbS in spite of the multiple contact site mutations in the α-chain. We conclude that the design of antisickling Hbs for gene therapy of sickle cell disease should involve multiple mutations of intermolecular contact sites.

  7. Molecular basis of Acute Myelogenous Leukemia As bases moleculares da leucemia mielóide aguda

    Directory of Open Access Journals (Sweden)

    Eduardo M. Rego

    2002-01-01

    Full Text Available Acute Myelogenous Leukemia (AML is frequently associated with recurring chromosomal translocations, which lead to the fusion of two genes encoding transcription factors. As the moieties of these fusion proteins retain part of the functional domains of the wild-type proteins, they may interfere directly or indirectly with the transcriptional regulation of the leukemic cell, conferring survival advantage. The majority of the transcription factors commonly involved in recurring chromosomal translocations may be grouped in one of the following families: core binding factor (CBF, retinoic acid receptor alpha (RARalpha, homeobox (HOX family, and mixed lineage leukemia (MLL. In vivo analysis of the molecular basis of leukemogenesis through the generation of transgenic mouse models revealed that a common theme is the recruitment of transcriptional co-activators and co-repressors by these fusion proteins. However, the expression of the fusion protein is not sufficient to induce full blown leukemia, as evidenced in part by the long latencies required for disease development in the transgenic models of leukemia, and therefore, second mutagenic events may contribute to AML pathogenesis.A leucemia mielóide aguda (LMA está freqüentemente associada a translocações cromossômicas recorrentes. Em muitos casos, os genes presentes nos pontos de quebra cromossômica são conhecidos e, quase todos codificam para fatores de transcrição. O gene híbrido, resultante da justaposição de exons de genes distintos, codifica para proteínas de fusão. Como estas retêm a maior parte dos domínios funcionais das proteínas selvagens, elas interferem direta ou indiretamente com regulação da transcrição gênica, conferindo vantagem à sobrevivência das células leucêmicas. A maioria dos fatores de transcrição afetados pelas translocações cromossômicas associadas a LMA pode ser agrupada numa das seguintes famílias: dos core binding factors (CBF, do receptor

  8. Elevated Hb A₂ Levels in a Patient with a Compound Heterozygosity for the (β⁺) -31 (A > G) and (β⁰) Codon 17 (A > T) Mutations Together with a Single α-Globin Gene.

    Science.gov (United States)

    Panyasai, Sitthichai; Jaiping, Kanokwan; Pornprasert, Sakorn

    2015-01-01

    We report the molecular and hematological feature of a Thai woman who had clinical diagnosis of β-thalassemia intermedia (β-TI). Hemoglobin (Hb) high performance liquid chromatography (HPLC) analysis identified Hb A (64.4%), Hb F (12.3%) and Hb A2/E (15.9%) with small peaks of Hb Bart's (γ4) and Hb H (β4). She was initially diagnosed as EA Bart's disease, which occurs from combination of Hb H disease and Hb E (HBB: c.79G > A) trait. However, the Hb analysis using capillary electrophoresis (CE) demonstrated no Hb E, 68.5% Hb A, 15.5% Hb F and 16.0% Hb A2. DNA analysis showed a compound heterozygosity for (β(+)) -31 (A > G) (HBB: c.-81A > G) and (β(0)) codon 17 (A > T) (HBB: c.52A > T) mutations and deletional Hb H (- -(SEA)/-α(3.7)). Thus, she was finally diagnosed with a combination of Hb H disease and compound heterozygosity of β(+)/β(0)-thalassemia (β(+)/β(0)-thal). The β-globin mutations could affect not only hematological parameters but also elevate the Hb A2 levels. These effects could not be ameliorated by the coinheritance of Hb H disease. Therefore, a better understanding of the effects of this combination on hematological analysis data will be useful for providing accurate diagnosis, genetic counseling, prevention and control programs of β-thalassemia major (β-TM).

  9. Both Autocrine Signaling and Paracrine Signaling of HB-EGF Enhance Ocular Neovascularization.

    Science.gov (United States)

    Inoue, Yuki; Shimazawa, Masamitsu; Nakamura, Shinsuke; Takata, Shinsuke; Hashimoto, Yuhei; Izawa, Hiroshi; Masuda, Tomomi; Tsuruma, Kazuhiro; Sakaue, Tomohisa; Nakayama, Hironao; Higashiyama, Shigeki; Hara, Hideaki

    2018-01-01

    The incidence of blindness is increasing because of the increase in abnormal ocular neovascularization. Anti-VEGF (vascular endothelial growth factor) therapies have led to good results, although they are not a cure for the blindness. The purpose of this study was to determine what role HB-EGF (heparin-binding epidermal growth factor-like growth factor) plays in ocular angiogenesis. We examined the role played by HB-EGF in ocular neovascularization in 2 animal models of neovascularization: laser-induced choroidal neovascularization (CNV) and oxygen-induced retinopathy. We also studied human retinal microvascular endothelial cells in culture. Our results showed that the neovascularization was decreased in both the CNV and oxygen-induced retinopathy models in HB-EGF conditional knockout mice compared with that in wild-type mice. Moreover, the expressions of HB-EGF and VEGF were increased after laser-induced CNV and oxygen-induced retinopathy, and their expression sites were located around the neovascular areas. Exposure of human retinal microvascular endothelial cells to HB-EGF and VEGF increased their proliferation and migration, and CRM-197 (cross-reactive material-197), an HB-EGF inhibitor, decreased the HB-EGF-induced and VEGF-induced cell proliferation and migration. VEGF increased the expression of HB-EGF mRNA. VEGF-dependent activation of EGFR (epidermal growth factor receptor)/ERK1/2 (extracellular signal-regulated kinase 1/2) signaling and cell proliferation of endothelial cells required stimulation of the ADAM17 (a disintegrin and metalloprotease) and ADAM12. CRM-197 decreased the grades of the fluorescein angiograms and size of the CNV areas in marmoset monkeys. These findings suggest that HB-EGF plays an important role in the development of CNV. Therefore, further investigations of HB-EGF are needed as a potential therapeutic target in the treatment of exudative age-related macular degeneration. © 2017 American Heart Association, Inc.

  10. The immunogenicity and safety of the new, Indonesian DTwP-HB-Hib vaccine compared to the DTwP/HB vaccine given with the Hib vaccine

    Directory of Open Access Journals (Sweden)

    Novilia Sjafri Bachtiar

    2017-06-01

    Full Text Available Background Haemophilus influenzae type b (Hib causes infection with predominant manifestations of pneumonia, meningitis, and other invasive diseases, occurring primarily in children aged under 2 years, particularly in infants.  The World Health Organization (WHO and Indonesian Technical Advisory Group for Immunization recommend to include the Hib vaccine into the national immunization program. The newly developed DTwP-HB-Hib combination vaccine is anticipated to be the preferred choice for Hib vaccine introduction; it is efficient, simple, and has higher coverage. Objective To evaluate the immunogenicity and safety of a new, combined Bio Farma DTwP-HB-Hib vaccine, compared to the registered Hib monovalent vaccine given simultaneously with the local DTwP-HB vaccine, when used as the primary vaccination of Indonesian infants. Methods A prospective, randomized, open-label, phase II study was conducted on the DTwP-HB-Hib vaccine compared to the Hib (registered vaccine given simultaneously with the DTwP-HB vaccine, in Bandung from July 2011 to January 2012. Infants were serially vaccinated at 6-11, 10-15, and 14-19 weeks. Serological assessments were done prior to the first vaccine dose and 28 days after the third dose. Safety was assessed from the time of first injection until 1 month after the last injection. Results Of 220 healthy infants enrolled, 211 completed the study, with 105 receiving the combined vaccine and 106 the two separate vaccines. All vaccines were well tolerated. No differences in rates of local and systemic reactions were seen between the two methods of administration. No serious adverse events were considered to be related to the vaccines. In the DTwP-HB-Hib primary-vaccination group, at least 98% of the infants reached protective levels of antibodies (seropositivity against the antigens employed in the vaccines while 96% in the control group. Conclusion The DTwP-HB-Hib combined vaccine is immunogenic and safe, as well as

  11. Description of Three New α Variants and Four New β Variants: Hb Montluel [α110(G17)Ala → Val; HBA1: c.332C > T], Hb Cap d'Agde [α131(H14)Ser → Cys; HBA2: c.395C > G] and Hb Corsica [α100(G7)Leu → Pro; HBA1: 302T > C]; Hb Nîmes [β104(G6)Arg → Gly; HBB: c.313A > G], Hb Saint Marcellin [β112(G14)Cys → Gly; HBB: c.337T > G], Hb Saint Chamond [β80(EF4)Asn → 0; HBB: c.241_243delAAC] and Hb Dompierre [β29(B11)Gly → Arg; HBB: c.88G > C].

    Science.gov (United States)

    Renoux, Céline; Feray, Cécile; Joly, Philippe; Lacan, Philippe; Francina, Alain

    2015-01-01

    We present here seven new hemoglobin (Hb) variants identified during routine Hb analysis. All of them are caused by a missense mutation except Hb Saint Chamond, which results from an in-frame deletion of the asparagine residue at β80. All these variants are clinically silent in the heterozygous state but two of them (Hb Cap d'Agde and Hb Dompierre) may be unstable, whereas Hb Nîmes could present a very slightly elevated oxygen affinity. These data are to be confirmed by appropriate biochemical tests.

  12. On the Da Vinci size effect in tensile strengths of nanowires: A molecular dynamics study

    Science.gov (United States)

    Zhao, Ziyu; Liu, Jinxing; Soh, Ai Kah

    2018-01-01

    In recent decades, size effects caused by grain size, strain gradient, typical defects etc., have been widely investigated. Nevertheless, the dependence of tensile strength on the specimen length, addressed by Da Vinci around 500 hundred years ago, has received rather limited attention, even though it is one unavoidable question to answer if people attempt to bring materials' amazing nano-scale strengths up to macro-level. Therefore, we make efforts to study tensile behaviors of copper nanowires with a common cross-section and various lengths by employing the molecular dynamics simulations. Surprisingly, a strong size effect of Da Vinci type indeed arises. We have shown the influences of lattice orientation, temperature and prescribed notch on such a Da Vinci size effect. Two different theoretical explanations are briefly proposed for a qualitative understanding. Finally, a simple scaling rule is summarized to cover the tendencies observed.

  13. Posterior transverse interarch discrepancy on HbE β thalassemia patients

    Directory of Open Access Journals (Sweden)

    Yuniar Zen

    2011-03-01

    Full Text Available Background: One of the symptoms that often arises on thalassemia patients is disharmony dentofacial, class II skeletal malocclusion, as a result of the malrelation of maxilla and mandible. This malrelation can be affected by either maxillary bone position, dentoalveolar maxillary position, mandibular bone position, dentoalveolar mandibular position, or combinations of those components. Purpose: The study was aimed to examine whether there is posterior transverse interarch discrepancy on the HbE β thalassemia patients or not. Methods: This study is an observational research with cross-sectional design. The sample consisted of 33 HbE β thalassemia patients and 33 non-thalassemia patients as a control group aged 12–14 years. Lateral cephalogram was carried out and dental casts of maxillary and mandibular dental arches were also taken in all of those patients. Results: There was no difference between the maxillary intermolar width of the HbE β thalassemia patients and that of the normal ones, but the mandibular intermolar width of the HbE β thalassemia patients was significantly smaller than that of the normal ones. Beside that, posterior transverse interarch discrepancy of of the HbE β thalassemia patients was significantly greater than that of the normal ones, which showed great difference between maxillary and mandibular intermolar widths. Conclusion: Posterior transverse interarch discrepancy of the HbE β thalassemia patients was different from that of the normal ones. The dentofacial abnormalities on the HbE β thalassemia patients aged 12–14 years primarily was due to disporposional dentofacial growth in the vertical, sagittal, and transversal directions, especially in the posterior region.Latar belakang: Salah satu akibat yang sering timbul pada penderita talasemia adalah disharmoni dentofasial berupa maloklusi skeletal kelas II yang merupakan kelainan hubungan maksila dan mandibula. Malrelasi ini dapat dipengaruhi oleh posisi

  14. Nota sobre antígeno relacionado à hepatite (HB Ag e anticorpo (HB Ab em população do território Federal do Amapá

    Directory of Open Access Journals (Sweden)

    Hermann G. Schatzmayr

    1974-04-01

    Full Text Available 53 amostras de soro, provenientes de Ferreira Gomes, no Amapá, foram testados para antígeno HB Ag e anticorpo HB Ab, com uma positividade de 3,7% para HB Ag, sub-tipo D. Os autores acentuam a necessidade de inquéritos em populações brasileiras a fim de estabelecer os sub-tipos associados à hepatite.3,7% of 53 serum samples from healthy inhabitants of Ferreira Gomes, Amapá, were positive for HB Ag, subtype D. The authors síress the needs of surveys to deteet the prevalent types of antigens associated with viral hepatitis in different areas of Brazil.

  15. HbA1c, fasting plasma glucose and the prediction of diabetes

    DEFF Research Database (Denmark)

    Soulimane, Soraya; Simon, Dominique; Shaw, Jonathan

    2012-01-01

    With diabetes defined by HbA1c≥6.5% and/or FPG≥7.0mmol/l and/or diabetes treatment, we investigated HbA1c and fasting plasma glucose (FPG) thresholds/change-points above which the incidence of diabetes increases.......With diabetes defined by HbA1c≥6.5% and/or FPG≥7.0mmol/l and/or diabetes treatment, we investigated HbA1c and fasting plasma glucose (FPG) thresholds/change-points above which the incidence of diabetes increases....

  16. Cell model for the study of receptor and regulatory functions of human proHB-EGF

    Directory of Open Access Journals (Sweden)

    N. V. Korotkevych

    2014-08-01

    Full Text Available Developing of new models and approaches, particularly with fluorescent techniques, for investigation of intracellular transport of proHB-EGF and its ligand-receptor complexes is strongly required. In order to create a model for studying proHB-EGF functions the genetic construction pEGFP-N1-proHB-EGF, encoding proHB-EGF-EGFP which is fluorescent-labeled form of proHB-EGF with enhanced green fluorescent protein EGFP in the cytoplasmic terminus of the molecule, was obtained. Eukaryotic cells expressing fusion protein proHB-EGF-EGFP on the cell surface were obtained by transfection with pEGFP-N1-proHB-EGF. Expressed in the Vero cells proHB-EGF-EGFP could bind fluorescent derivative of nontoxic receptor-binding subunit B of diphtheria toxin mCherry-SubB. After stimulation of transfected cells with TPA (12-O-Tetradecanoylphorbol-13-acetate, proHB-EGF-EGFP formed a fluorescentl-labeled C-terminal fragment of the molecule – CTF-EGFP. Thus, the obtained genetic construction pEGFP-N1-proHB-EGF could be helpful in visualization of molecules proHB-EGF and CTF in cells, may open new possibilities for the studying of their functions, such as receptor function of proHB-EGF for diphtheria toxin, intracellular translocation of CTF and provide possibilities for natural proHB-EGF ligands search.

  17. Impact of Mean Cell Hemoglobin on Hb A1c-Defined Glycemia Status.

    Science.gov (United States)

    Rodriguez-Segade, Santiago; Garcia, Javier Rodriguez; García-López, José M; Gude, Francisco; Casanueva, Felipe F; Rs-Alonso, Santiago; Camiña, Félix

    2016-12-01

    Several hematological alterations are associated with altered hemoglobin A 1c (Hb A 1c ). However, there have been no reports of their influence on the rates of exceeding standard Hb A 1c thresholds by patients for whom Hb A 1c determination is requested in clinical practice. The initial data set included the first profiles (complete blood counts, Hb A 1c , fasting glucose, and renal and hepatic parameters) of all adult patients for whom such a profile was requested between 2008 and 2013 inclusive. After appropriate exclusions, 21844 patients remained in the study. Linear and logistic regression models were adjusted for demographic, hematological, and biochemical variables excluded from the predictors. Mean corpuscular hemoglobin (MCH) and mean corpuscular volume (MCV) correlated negatively with Hb A 1c . Fasting glucose, MCH, and age emerged as predictors of Hb A 1c in a stepwise regression that discarded sex, hemoglobin, MCV, mean corpuscular hemoglobin concentration (MCHC), serum creatinine, and liver disease. Mean Hb A 1c in MCH interdecile intervals fell from 6.8% (51 mmol/mol) in the lowest (≤27.5 pg) to 6.0% (43 mmol/mol) in the highest (>32.5 pg), with similar results for MCV. After adjustment for fasting glucose and other correlates of Hb A 1c , a 1 pg increase in MCH reduced the odds of Hb A 1c -defined dysglycemia, diabetes and poor glycemia control by 10%-14%. For at least 25% of patients, low or high MCH or MCV levels are associated with increased risk of an erroneous Hb A 1c -based identification of glycemia status. Although causality has not been demonstrated, these parameters should be taken into account in interpreting Hb A 1c levels in clinical practice. © 2016 American Association for Clinical Chemistry.

  18. Hb San Cataldo [β144(HC1)Lys→Thr; HBB: C.434A > C]: A New Hemoglobin Variant with Increased Affinity for Oxygen.

    Science.gov (United States)

    Vinciguerra, Margherita; Passarello, Cristina; Cassarà, Filippo; Leto, Filippo; Cannata, Monica; Crivello, Anna; Di Salvo, Veronica; Maggio, Aurelio; Giambona, Antonino

    2016-08-01

    A 59-year-old Italian woman came to our center for revaluation of a previous diagnosis of polycythemia vera. The patient presented with a lifelong history of polycythemia, no increase in white blood cells (WBCs) and platelets, and a negative bone marrow biopsy. Analysis of hemoglobin (Hb) fractions showed an abnormal fast moving Hb component. We aimed to determine if this variant was the cause of polycythemia in this patient. A complete blood count (CBC) was performed by an automated cell counter and Hb fractions were determined by high performance liquid chromatography (HPLC). Standard stability tests and oxygen affinity evaluation were also performed. Genomic DNA was extracted from peripheral blood leukocytes using the phenol chloroform method and the entire β-globin gene was analyzed by direct sequencing. At the hematological level, no anemia or hemolysis was observed but an abnormal Hb fraction was detected using cation exchange HPLC. Molecular analysis of the β-globin gene showed heterozygosity for an AAG > ACG substitution at codon 144, resulting in a Lys→Thr amino acid replacement. We demonstrated that this is a new Hb variant with increased oxygen affinity. Its altered physiology is caused by the reduction of 2,3-diphosphoglycerate (2,3-DPG) effects, due to an amino acid substitution in the central pocket near the C-terminal of the β chain. We called this new variant Hb San Cataldo for the native city of proband.

  19. HbA1c for diagnosis and prognosis of gestational diabetes mellitus.

    Science.gov (United States)

    Kwon, Soon Sung; Kwon, Ja-Young; Park, Yong-Won; Kim, Young-Han; Lim, Jong-Baeck

    2015-10-01

    HbA1c is a widely used marker in diagnosing type 2 diabetes mellitus (DM), but its clinical utility in diagnosing gestational diabetes mellitus (GDM) is not established. Here, we evaluated the clinical usefulness of HbA1c in diagnosing GDM and predicting the risk of future type 2 DM development among GDM patients. This retrospective, cross-sectional study included 321 subjects who underwent 100-g oral glucose tolerance tests (OGTT) during pregnancy. HbA1c and other variables were analyzed to evaluate their diagnostic performance for GDM. To evaluate the clinical usefulness of HbA1c in predicting future type 2 DM development, we classified GDM subjects who had more than 3 months of follow-up data into two subgroups: those who developed postpartum type 2 DM (PDM) and those who did not. HbA1c was significantly higher in the GDM group than in the normal control group. With the 100-g OGTT as reference, HbA1c showed 91.3% sensitivity and 62% specificity at a cut-off value of 5.05% (32 mmol/mol) for GDM diagnosis. At a cut-off value of 5.25% (34 mmol/mol), sensitivity was 73.6% and specificity was 77.2%. HbA1c levels during pregnancy were higher in those with PDM than in those without PDM (5.91 [41 mmol/mol] vs. 5.44% [36 mmol/mol], p<0.001). The prognostic value of HbA1c for PDM was evaluated by ROC curve analysis, with sensitivity of 78.6% and specificity of 72.5% at a cut-off value of 5.55% (37 mmol/mol). HbA1c showed high sensitivity with relatively low specificity for diagnosis of GDM in pregnant women and was a potential predictor of PDM. HbA1c may be able to be used as a simple and less invasive alternative screening test for OGTT in GDM patients. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  20. Características fenotípicas dos pacientes com anemia falciforme de acordo com os haplótipos do gene da βS-globina em Fortaleza, Ceará

    Directory of Open Access Journals (Sweden)

    Lilianne B. Silva

    2010-02-01

    Full Text Available Foram analisados 47 pacientes com diagnóstico clínico, laboratorial e molecular de anemia falciforme, residentes em Fortaleza, Ceará, com a finalidade de fornecer informações sobre a influência dos haplótipos do gene da βS- globina nas características fenotípicas desta doença. A determinação dos valores hematológicos foi realizada em contador automático de células sanguíneas, e os níveis de HbF foram determinados pela técnica da desnaturação alcalina. O DNA foi isolado de leucócitos, a partir de amostras de sangue total. A análise dos haplótipos da mutação βS foi realizada por PCR-RFLP (Polymerase Chain Reaction-Restriction Fragment Lenght Polymorphism, sendo analisados seis sítios polimórficos de restrição. Os pacientes foram divididos em cinco grupos, de acordo com o tipo de haplótipo: Bantu/Bantu, Benin/Benin, Bantu/Benin, Bantu/Atípico e Benin/Atípico. O nível de significância considerado nas análises foi p<0,05. Na comparação entre os haplótipos e as características hematológicas estudadas, apenas os valores de HbF e Ht apresentaram diferença estatisticamente significativa. Os níveis de HbF foram maiores no haplótipo Benin, seguido do haplótipo Bantu, o que está em conformidade com os dados da literatura. Foram demonstrados maior presença de crises vaso-oclusivas e episódios de pneumonia no haplótipo Benin/Atípico do que no haplótipo Bantu/Atípico; e maior presença de crises de infecção urinária no haplótipo Benin/Atípico do que no haplótipo Benin/Benin. Não houve diferença estatisticamente significativa entre os haplótipos Bantu/Bantu e Benin/Benin em relação às complicações clínicas; entretanto, foi observado que o haplótipo Bantu/Bantu tem uma maior frequência em todos os eventos clínicos estudados quando comparado ao Benin/Benin. Os resultados demonstram que o tipo de haplótipo do gene da βS-globina influencia as características fenotípicas dos pacientes com

  1. Evaluation of the DCA Vantage analyzer for HbA 1c assay.

    Science.gov (United States)

    Szymezak, Jean; Leroy, Nathalie; Lavalard, Emmanuelle; Gillery, Philippe

    2008-01-01

    Measurement of HbA 1c is key in monitoring diabetic patients in both laboratories and clinical units, where HbA 1c results are used as part of patient education. We have evaluated the DCA Vantage, a new device for immunological assay of HbA 1c. HbA 1c results obtained were evaluated in terms of precision, linearity, specificity and practicability, and were compared with results obtained by a Variant II HPLC method. The method exhibited intra- and inter-assay coefficients of variation lower than 2.6% and 4.0%, respectively, and good correlation with the comparison HPLC method (r2=0.9776). No interference was noted in the presence of labile HbA 1c or carbamylated hemoglobin. The new device exhibited improved practicability characteristics and allowed better sample identification, better management of quality control routines and greater connectivity possibilities compared to the previous DCA 2000 analyzer. This new analyzer exhibited analytical and practical characteristics very suitable for HbA 1c assay for laboratory or point-of-care use according to good laboratory practice.

  2. Analysis of HbA1c on an automated multicapillary zone electrophoresis system.

    Science.gov (United States)

    Rollborn, Niclas; Åkerfeldt, Torbjörn; Nordin, Gunnar; Xu, Xiao Yan; Mandic-Havelka, Aleksandra; Hansson, Lars-Olof; Larsson, Anders

    2017-02-01

    Hemoglobin A1c (HbA1c) is a frequently requested laboratory test and there is thus a need for high throughput instruments for this assay. We evaluated a new automated multicapillary zone electrophoresis instrument (Capillarys 3 Tera, Sebia, Lisses, France) for analysis of HbA1c in venous samples. Routine requested HbA1c samples were analyzed immunologically on a Roche c6000 instrument (n = 142) and then with the Capillarys 3 Tera instrument. The Capillarys 3 Tera instrument performed approximately 70 HbA1c tests/hour. There was a strong linear correlation between Capillarys 3 Tera and Roche Tina-Quant HbA1c Gen 3 assay (y = 1.003x - 0.3246 R 2  = .996). The total CV for the 12 capillaries varied between 0.8 and 2.2% and there was a good agreement between duplicate samples (R 2  = .997). In conclusion, the Capillarys 3 Tera instrument has a high assay capacity for HbA1c. It has a good precision and agreement with the Roche Tina-Quant HbA1c method and is well suited for high volume testing of HbA1c.

  3. On the Da Vinci size effect in tensile strengths of nanowires: A molecular dynamics study

    Directory of Open Access Journals (Sweden)

    Ziyu Zhao

    2018-01-01

    Full Text Available In recent decades, size effects caused by grain size, strain gradient, typical defects etc., have been widely investigated. Nevertheless, the dependence of tensile strength on the specimen length, addressed by Da Vinci around 500 hundred years ago, has received rather limited attention, even though it is one unavoidable question to answer if people attempt to bring materials’ amazing nano-scale strengths up to macro-level. Therefore, we make efforts to study tensile behaviors of copper nanowires with a common cross-section and various lengths by employing the molecular dynamics simulations. Surprisingly, a strong size effect of Da Vinci type indeed arises. We have shown the influences of lattice orientation, temperature and prescribed notch on such a Da Vinci size effect. Two different theoretical explanations are briefly proposed for a qualitative understanding. Finally, a simple scaling rule is summarized to cover the tendencies observed.

  4. Single amino acid substitution in important hemoglobinopathies does not disturb molecular function and biological process

    Directory of Open Access Journals (Sweden)

    Viroj Wiwanitkit

    2008-06-01

    Full Text Available Viroj WiwanitkitDepartment of Laboratory Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, ThailandAbstract: Hemoglobin is an important protein found in the red cells of many animals. In humans, the hemoglobin is mainly distributed in the red blood cell. Single amino acid substitution is the main pathogenesis of most hemoglobin disorders. Here, the author used a new gene ontology technology to predict the molecular function and biological process of four important hemoglobin disorders with single substitution. The four studied important abnormal hemoglobins (Hb with single substitution included Hb S, Hb E, Hb C, and Hb J-Baltimore. Using the GoFigure server, the molecular function and biological process in normal and abnormal hemoglobins was predicted. Compared with normal hemoglobin, all studied abnormal hemoglobins had the same function and biological process. This indicated that the overall function of oxygen transportation is not disturbed in the studied hemoglobin disorders. Clinical findings of oxygen depletion in abnormal hemoglobin should therefore be due to the other processes rather than genomics, proteomics, and expression levels.Keywords: hemoglobin, amino acid, substitution, function

  5. The isolation of the γ subunit of fetal hemoglobin (HbF) and its use in a radioimmunoassay for HbF

    International Nuclear Information System (INIS)

    James, R.F.L.; Shuster, J.; Freedman, S.O.; Gold, P.

    1980-01-01

    A method is described for the purification, from fetal hemoglobin (HbF), of the fetal specific globin chain (γ chain) in its native state. In the absence of α chain (the globin chain common to all adult human hemoglobins) γ chain, when used as an immunogen, is able to express its unique antigenicity. Here, a specific, high titer antiserum raised against γ chain has been used to establish a sensitive radioimmunoassay for HbF. This approach may be applicable to the measurement of other normal and abnormal hemoglobins. (Auth.)

  6. ESTUDO DOS COMPRIMENTOS DE LIGAÇÃO DA FORMA CETÔNICA DA CURCUMINA NO VÁCUO USANDO DINÂMICA MOLECULAR DE CAR-PARRINELLO

    Directory of Open Access Journals (Sweden)

    Eduardo MartinsToledo

    2015-03-01

    Full Text Available A curcumina é um pigmento amarelo-laranja extraído do rizoma da planta Curcuma longa L. Tem-se destacado por apresentar um amplo potencial terapêutico, com atividade antibacteriana, anti-inflamatória, antioxidante, pró-apoptótica, quimiopreventiva, anticarcinogênica entre outras. Apesar das diversas propriedades biológicas identificadas, existem poucos estudos teóricos sobre este candidato a fármaco. Nesse sentido, o presente trabalho objetivou-se no estudo dos comprimentos de ligação da forma cetônica da curcumina no vácuo, utilizando o método de Dinâmica Molecular de Car-Parrinello. Para os cálculos, a molécula foi disposta em uma caixa cúbica, com dimensões de 23 Å. O funcional de energia de troca e correlação foi modelado usando o funcional do gradiente corrigido PBE. Os elétrons do núcleo foram tratados com pseudopotenciais ultrasolf de Vanderbilt, e os de valência foram representados pelo conjunto de funções de base em ondas planas, truncadas em energia cinética de corte de 20 Ry. As simulações de DMCP foram realizadas a 300 K, com um passo de integração de 6,0 a.t.u. e massa fictícia de 500 a.u. Os resultados mostram uma boa concordância com as propriedades estruturais da forma cetônica da curcumina determinadas por outros métodos teóricos. Este estudo contribui para a compreensão inicial das propriedades estruturais da forma cetônica da curcumina.

  7. Hb A1c Separation by High Performance Liquid Chromatography in Hemoglobinopathies

    Directory of Open Access Journals (Sweden)

    Vani Chandrashekar

    2016-01-01

    Full Text Available Hb A1c measurement is subject to interference by hemoglobin traits and this is dependent on the method used for determination. In this paper we studied the difference between Hb A1c measured by HPLC in hemoglobin traits and normal chromatograms. We also studied the correlation of Hb A1c with age. Hemoglobin analysis was carried out by high performance liquid chromatography. Spearman’s rank correlation was used to study correlation between A1c levels and age. Mann-Whitney U test was used to study the difference in Hb A1c between patients with normal hemoglobin and hemoglobin traits. A total of 431 patients were studied. There was positive correlation with age in patients with normal chromatograms only. No correlation was seen in Hb E trait or beta thalassemia trait. No significant difference in Hb A1c of patients with normal chromatograms and patients with hemoglobin traits was seen. There is no interference by abnormal hemoglobin in the detection of A1c by high performance liquid chromatography. This method cannot be used for detection of A1c in compound heterozygous and homozygous disorders.

  8. HB+ prepares for insertion into the CMS solenoid

    CERN Multimedia

    Dave Barney, CERN

    2006-01-01

    With calibration of the first half of the barrel Hadron Calorimeter (HB+) complete (using a radioactive source), preparations begin for its insertion into the solenoid for the Magnet Test and Cosmic Challenge (MTCC). It was moved out of its alcove at the beginning of March - a non-trivial (but completely successful) operation due to the proximity of one of the barrel yoke rings (YB+1). The other half of the barrel Hadron Calorimeter (HB-) and one of the endcaps (HE+) should also be calibrated before the MTCC.

  9. HB+ inserted into the CMS Solenoid

    CERN Multimedia

    Tejinder S. Virdee, CERN

    2006-01-01

    The first half of the barrel hadron calorimeter (HB+) has been inserted into the superconducting solenoid of CMS, in preparation for the magnet test and cosmic challenge. The operation went smoothly, lasting a couple of days.

  10. Serum levels of antioxidant vitamins in foetal haemoglobin (HbF ...

    African Journals Online (AJOL)

    Background: sickle cell anaemia (SCA) is one of the commonest health problems of Nigerian children. Method: The serum levels of antioxidant vitamins A (retinol), C (ascorbic acid) and E (alpha-tocopherol) were determined in foetal haemogbobin persistent sickle cell anaemic (Hb SS + F), sickle cell anaemic (Hb SS) and ...

  11. Molecular controls of the oxygenation and redox reactions of hemoglobin.

    Science.gov (United States)

    Bonaventura, Celia; Henkens, Robert; Alayash, Abdu I; Banerjee, Sambuddha; Crumbliss, Alvin L

    2013-06-10

    The broad classes of O(2)-binding proteins known as hemoglobins (Hbs) carry out oxygenation and redox functions that allow organisms with significantly different physiological demands to exist in a wide range of environments. This is aided by allosteric controls that modulate the protein's redox reactions as well as its O(2)-binding functions. The controls of Hb's redox reactions can differ appreciably from the molecular controls for Hb oxygenation and come into play in elegant mechanisms for dealing with nitrosative stress, in the malarial resistance conferred by sickle cell Hb, and in the as-yet unsuccessful designs for safe and effective blood substitutes. An important basic principle in consideration of Hb's redox reactions is the distinction between kinetic and thermodynamic reaction control. Clarification of these modes of control is critical to gaining an increased understanding of Hb-mediated oxidative processes and oxidative toxicity in vivo. This review addresses emerging concepts and some unresolved questions regarding the interplay between the oxygenation and oxidation reactions of structurally diverse Hbs, both within red blood cells and under acellular conditions. Developing methods that control Hb-mediated oxidative toxicity will be critical to the future development of Hb-based blood substitutes.

  12. Prevalence and predictors of the sub-target Hb level in children on dialysis

    DEFF Research Database (Denmark)

    van Stralen, Karlijn J; Krischock, Leah; Schaefer, Franz

    2012-01-01

    Anaemia is a common and potentially treatable co-morbidity of end-stage renal disease. We aimed to determine the prevalence of the sub-target haemoglobin (Hb) level among European children on dialysis and to identify factors associated with a low Hb level.......Anaemia is a common and potentially treatable co-morbidity of end-stage renal disease. We aimed to determine the prevalence of the sub-target haemoglobin (Hb) level among European children on dialysis and to identify factors associated with a low Hb level....

  13. A Family with γ-Thalassemia and High Hb A2 Levels.

    Science.gov (United States)

    Parmeggiani, Giulia; Gualandi, Francesca; Selvatici, Rita; Rimessi, Paola; Bigoni, Stefania; Taddei Masieri, Marina; Dolcini, Bernadetta; Venturoli, Anna; Cappabianca, Maria P; Ferlini, Alessandra; Ravani, Anna

    2016-06-01

    We describe a family carrying a γ-globin gene deletion associated with an increase of Hb A2 level beyond the normal range. The family included the proband, his sister and their father, all with increased Hb A2 and normal Hb F levels. The proband and his sister showed borderline values of mean corpuscular volume (MCV) and reduced values of mean corpuscular hemoglobin (Hb) (MCH). The proband was referred to our Medical Genetics Service for preconception counseling together with his partner, a typical β-thalassemia (β-thal) carrier. The results were negative for the most frequent α-thalassemia (α-thal) mutations, and had no significant sequence variations of the coding sequences and promoter of the β- and δ-globin genes. Quantitative analysis by multiplex ligation-dependent probe amplification (MPLA) of the β-globin gene cluster detected a heterozygous deletion, ranging between 2.1 and 4.7 kb, in the proband, his sister and the father. The deletion involved the (G)γ gene and (G)γ-(A)γ intergenic region, whereas the 3' region of the (A)γ gene was preserved. A subsequent gap-polymerase chain reaction (gap-PCR) showed that a hybrid (GA)γ fusion gene was present. The deletion segregated with the elevation of Hb A2. The MLPA analysis of the β-globin gene cluster in 150 control alleles excluded a common polymorphism. Despite stronger evidence being needed, the described family suggests a possible role of this γ-globin gene deletion in contributing to Hb A2 elevation, possibly by altering the transcription regulation of the cluster. We propose γ-globin gene dosage analysis to be performed in patients with unexplained elevated Hb A2 levels.

  14. HbA1c levels in individuals heterozygous for hemoglobin variants.

    Science.gov (United States)

    Tavares, Ricardo Silva; Souza, Fábio Oliveira de; Francescantonio, Isabel Cristina Carvalho Medeiros; Soares, Weslley Carvalho; Mesquita, Mauro Meira

    2017-04-01

    To evaluate the levels of glycated hemoglobin (HbA1c) in patients heterozygous for hemoglobin variants and compare the results of this test with those of a control group. This was an experimental study based on the comparison of HbA1c tests in two different populations, with a test group represented by individuals heterozygous for hemoglobin variants (AS and AC) and a control group consisting of people with electrophoretic profile AA. The two populations were required to meet the following inclusion criteria: Normal levels of fasting glucose, hemoglobin, urea and triglycerides, bilirubin > 20 mg/dL and non-use of acetylsalicylic acid. 50 heterozygous subjects and 50 controls were evaluated between August 2013 and May 2014. The comparison of HbA1c levels between heterozygous individuals and control subjects was performed based on standard deviation, mean and G-Test. The study assessed a test group and a control group, both with 39 adults and 11 children. The mean among heterozygous adults for HbA1c was 5.0%, while the control group showed a rate of 5.74%. Heterozygous children presented mean HbA1c at 5.11%, while the controls were at 5.78%. G-Test yielded p=0.93 for children and p=0.89 for adults. Our study evaluated HbA1c using ion exchange chromatography resins, and the patients heterozygous for hemoglobin variants showed no significant difference from the control group.

  15. HbA1c measurements from dried blood spots : validation and patient satisfaction

    NARCIS (Netherlands)

    Fokkema, Margaretha; Bakker, Andries J; de Boer, Fokje; Kooistra, Jeltsje; de Vries, Sifra; Wolthuis, Albert

    2009-01-01

    Background: This study evaluates HbA1c measurements from dried blood spots collected on filter paper and compares HbA1c from filter paper (capillary blood) with HbA1c measured in venous blood. Methods: Patient satisfaction was evaluated using a questionnaire. The performance with the filter paper

  16. Hb Presbyterian (HBB: c.327C>G) in a Nicaraguan Family.

    Science.gov (United States)

    Pernudy-Ubau, Allan; Salinas-Molina, Jaslyn; Requenez, Yaneris; Ortiz-Lopez, Marianela; Puller, Ann-Christin; García-Rosales, Kenia; Rodríguez-Estrada, Anaishelle; Rodríguez-Romero, Walter; Mejía-Baltodano, Gerardo; Luo, Hong-Yuan; Chui, David H K

    2017-01-01

    Hemoglobin (Hb) is the protein responsible for oxygen transportation. It is a tetrameric protein comprising two α- and two β-globin subunits. In the literature, a large number of mutations in the α- and β-globin genes have been documented. Among these mutations, Hb Presbyterian (HBB: c.327 C>G), is a naturally occurring mutant exerting low oxygen affinity. The C to G exchange (AAC>AAG) at codon 108 of the β-globin gene results in the substitution of asparagine by lysine. Here, we document the identification of HBB: c.327 C>G in a 6-year-old female patient and her father from Nicaragua and Cuba, respectively. The presence of the abnormal Hb was confirmed by cellulose acetate electrophoresis, high performance liquid chromatography (HPLC) and genomic DNA sequencing. The β-globin gene sequences for both, father and daughter, disclosed the heterozygous mutation at codon 108 to be Hb Presbyterian or HBB: c.327 C>G. The mutant Hb was previously reported in four families from North America, Germany, Japan and Spain, respectively. This is the fifth family carrying HBB: c.327 C>G described to date and the first report from Latin America.

  17. Two α1-Globin Gene Point Mutations Causing Severe Hb H Disease.

    Science.gov (United States)

    Jiang, Hua; Huang, Lv-Yin; Zhen, Li; Jiang, Fan; Li, Dong-Zhi

    Hb H disease is generally a moderate form of α-thalassemia (α-thal) that rarely requires regular blood transfusions. In this study, two Chinese families with members carrying transfusion-dependent Hb H disease were investigated for rare mutations on the α-globin genes (HBA1, HBA2). In one family, Hb Zürich-Albisrieden [α59(E8)Gly→Arg; HBA1: c.178G>C] in combination with the Southeast Asian (- - SEA ) deletion was the defect responsible for the severe phenotype. In another family, a novel hemoglobin (Hb) variant named Hb Sichuan (HBA1: c.393_394insT), causes α-thal and a severe phenotype when associated with the - - SEA deletion. As these two HBA1 mutations can present as continuous blood transfusion-dependent α-thal, it is important to take this point into account for detecting the carriers, especially in couples in which one partner is already a known α 0 -thal carrier.

  18. Helicobacter pylori-Induced HB-EGF Upregulates Gastrin Expression via the EGF Receptor, C-Raf, Mek1, and Erk2 in the MAPK Pathway

    Directory of Open Access Journals (Sweden)

    Niluka Gunawardhana

    2018-01-01

    Full Text Available Helicobacter pylori is associated with hypergastrinemia, which has been linked to the development of gastric diseases. Although the molecular mechanism is not fully understood, H. pylori is known to modulate the Erk pathway for induction of gastrin expression. Herein we found that an epidermal growth factor (EGF receptor kinase inhibitor significantly blocked H. pylori-induced gastrin promoter activity, suggesting involvement of EGF receptor ligands. Indeed, H. pylori induced mRNA expression of EGF family members such as amphiregulin, EGF, heparin-binding EGF-like growth factor (HB-EGF, and transforming growth factor-α. Of these, specific siRNA targeting of HB-EGF significantly blocked H. pylori-induced gastrin expression. Moreover, H. pylori induced HB-EGF ectodomain shedding, which we found to be a critical process for H. pylori-induced gastrin expression. Thus, we demonstrate a novel role for human mature HB-EGF in stimulating gastrin promoter activity during H. pylori infection. Further investigation using specific siRNAs targeting each isoform of Raf, Mek, and Erk elucidated that the mechanism underlying H. pylori-induced gastrin expression can be delineated as the sequential activation of HB-EGF, the EGF receptor, C-Raf, Mek1, and the Erk2 molecules in the MAPK pathway. Surprisingly, whereas Erk2 acts as a potent activator of gastrin expression, siRNA knockdown of Erk1 induced gastrin promoter activity, suggesting that Erk1 typically acts as a repressor of gastrin expression. Elucidation of the mechanism of gastrin modulation by HB-EGF-mediated EGF receptor transactivation should facilitate the development of therapeutic strategies against H. pylori-related hypergastrinemia and consequently gastric disease development, including gastric cancers.

  19. Helicobacter pylori-Induced HB-EGF Upregulates Gastrin Expression via the EGF Receptor, C-Raf, Mek1, and Erk2 in the MAPK Pathway.

    Science.gov (United States)

    Gunawardhana, Niluka; Jang, Sungil; Choi, Yun Hui; Hong, Youngmin A; Jeon, Yeong-Eui; Kim, Aeryun; Su, Hanfu; Kim, Ji-Hye; Yoo, Yun-Jung; Merrell, D Scott; Kim, Jinmoon; Cha, Jeong-Heon

    2017-01-01

    Helicobacter pylori is associated with hypergastrinemia, which has been linked to the development of gastric diseases. Although the molecular mechanism is not fully understood, H. pylori is known to modulate the Erk pathway for induction of gastrin expression. Herein we found that an epidermal growth factor (EGF) receptor kinase inhibitor significantly blocked H. pylori -induced gastrin promoter activity, suggesting involvement of EGF receptor ligands. Indeed, H. pylori induced mRNA expression of EGF family members such as amphiregulin, EGF, heparin-binding EGF-like growth factor (HB-EGF), and transforming growth factor-α. Of these, specific siRNA targeting of HB-EGF significantly blocked H. pylori -induced gastrin expression. Moreover, H. pylori induced HB-EGF ectodomain shedding, which we found to be a critical process for H. pylori -induced gastrin expression. Thus, we demonstrate a novel role for human mature HB-EGF in stimulating gastrin promoter activity during H. pylori infection. Further investigation using specific siRNAs targeting each isoform of Raf, Mek, and Erk elucidated that the mechanism underlying H. pylori -induced gastrin expression can be delineated as the sequential activation of HB-EGF, the EGF receptor, C-Raf, Mek1, and the Erk2 molecules in the MAPK pathway. Surprisingly, whereas Erk2 acts as a potent activator of gastrin expression, siRNA knockdown of Erk1 induced gastrin promoter activity, suggesting that Erk1 typically acts as a repressor of gastrin expression. Elucidation of the mechanism of gastrin modulation by HB-EGF-mediated EGF receptor transactivation should facilitate the development of therapeutic strategies against H. pylori -related hypergastrinemia and consequently gastric disease development, including gastric cancers.

  20. A conservative region of the mercuric reductase gene (merA as a molecular marker of bacterial mercury resistance Região conservada do gene da mercúrio redutase (merA como marcador molecular da resistência bacteriana ao mercúrio

    Directory of Open Access Journals (Sweden)

    Adriana Sotero-Martins

    2008-06-01

    Full Text Available The most common bacterial mercury resistance mechanism is based on the reduction of Hg(II to Hg0, which is dependent of the mercuric reductase enzyme (MerA activity. The use of a 431 bp fragment of a conservative region of the mercuric reductase (merA gene was applied as a molecular marker of this mechanism, allowing the identification of mercury resistant bacterial strains.O mecanismo de resistência bacteriana ao mercúrio mais comum é baseada na redução do Hg(II a Hg0, através da atividade da enzima mercúrio redutase (MerA. O uso do fragmento de 431 pb amplificado de uma região conservada do gene merA, que codifica a enzima MerA,foi utilizado como marcador molecular deste mecanismo, permitindo a identificação de bactérias resistentes ao mercúrio.

  1. Diagnostic accuracy of HbA1c in diabetes between Eastern and Western.

    Science.gov (United States)

    Yan, Shuang; Liu, Siying; Zhao, Yashuang; Zhang, Wencui; Sun, Xiaohui; Li, Jianing; Jiang, Fuli; Ju, Jiaming; Lang, Ning; Zhang, Yingqi; Zhou, Weiyu; Li, Qiang

    2013-07-01

    In 2010, the American Diabetes Association recommended the use of HbA1c as a diagnostic criterion for diabetes. However, HbA1c is not an accepted diagnostic tool for diabetes in Eastern Asia, because genetic differences compromise the standardization of the diagnostic cut-off point. This study evaluated differences in the use of HbA1c for diagnosing diabetes in Eastern and Western populations and investigated whether HbA1c cut-off point of ≥ 6.5% is diagnostic of diabetes in patients from Eastern Asia. Literature was obtained from MEDLINE, EMBASE and Cochrane databases. The pooled sensitivity and specificity of each HbA1c cut-off point were extracted and compared between Western and Eastern populations. Differences in the cut-off point for diagnosing diabetes in each region were compared by examining differences in the area under summary receiver operating characteristic (SROC) curves. Twelve publications from Eastern countries (n = 59,735) and 13 from Western countries (n = 22,954) were included in the analysis. Areas under SROC curves in the Eastern and Western groups were 0.9331 and 0.9120, respectively (P = 0.98). The cut-off point of the highest Youden index was 6.0%. At the HbA1c cut-off point of 6.5%, the pooled sensitivity and specificity were 58.7% and 98.4% for Eastern countries and 65.5% and 98.1% for Western countries, respectively. HbA1c exhibits the same diagnostic value for diabetes in Eastern and Western populations. In both populations, HbA1c levels > 6.0% identify the population at high risk of diabetes, and HbA1c > 6.5% is diagnostic of clinically established diabetes. © 2013 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd.

  2. HB-EGF is necessary and sufficient for Müller glia dedifferentiation and retina regeneration

    Science.gov (United States)

    Wan, Jin; Ramachandran, Rajesh; Goldman, Daniel

    2011-01-01

    Summary Müller glia (MG) dedifferentiation into a cycling population of multipotent progenitors is crucial to zebrafish retina regeneration. The mechanisms underlying MG dedifferentiation are unknown. Here we report that heparin-binding epidermal-like growth factor (HB-EGF) is rapidly induced in MG residing at the injury site and that proHB-EGF ectodomain shedding is necessary for retina regeneration. Remarkably, HB-EGF stimulates the formation of multipotent MG-derived progenitors in the uninjured retina. We show that HB-EGF mediates its effects via an EGFR/MAPK signal transduction cascade that regulates the expression of regeneration-associated genes, like ascl1a and pax6b. We also uncover an HB-EGF/Ascl1a/Notch/hb-egfa signaling loop that helps define the zone of injury-responsive MG. Finally, we show that HB-EGF acts upstream of the Wnt/β-catenin signaling cascade that controls progenitor proliferation. These data provide a link between extracellular signaling and regeneration-associated gene expression in the injured retina and suggest strategies for stimulating retina regeneration in mammals. PMID:22340497

  3. Role of HbA1c in predicting risk for congenital malformations.

    Science.gov (United States)

    Hammouda, Sahar Ali Ibrahim; Hakeem, Rubina

    2015-12-01

    Association between conventionally identified hyperglycemias and rates of congenital abnormalities is known; however there is less information about role of HbA1c in determining gestational hyperglycemias and associated risks. This study tried to explore the association between HbA1c in women without known diabetes at first antenatal visit and risk of congenital malformations (CM) among Saudi women living at Al-Madinah Al-Monawarah. Eleven hundred and eighty (1180), healthy, first-trimester pregnant Saudi females without known diabetes, were selected from various antenatal care clinics of Al-Madinah Al-Monawarah city. General clinical and biochemical data was collected for this study by researchers at first visit and the time of delivery. Nearly one fifth (19.6%) of mothers had above normal HbA1c (>5.7) at first visit. Rates of CM had significant positive association with level of HbA1c. Rate of CM among those who had HbA1c in diabetes range, pre-diabetes range or normal range was 27.8%, 9.8% and 3.0%, respectively. The difference was significant between normal and pre-diabetes at the level P=0.000 and between pre-diabetes and diabetes at level P=0.038. In this study HbA1c is found to be a valuable predictor of risk of congenital malformations. This observation calls for further studies and establishment of policies for care of pregnant mothers having higher than normal HbA1c at first visit. Copyright © 2015 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.

  4. Baseline Report on HB2320

    Science.gov (United States)

    State Council of Higher Education for Virginia, 2015

    2015-01-01

    Staff provides this baseline report as a summary of its preliminary considerations and initial research in fulfillment of the requirements of HB2320 from the 2015 session of the General Assembly. Codified as § 23-7.4:7, this legislation compels the Education Secretary and the State Council of Higher Education for Virginia (SCHEV) Director, in…

  5. 2,3-DPG-Hb complex: a hypothesis for an asymmetric binding.

    Science.gov (United States)

    Pomponi, M; Bertonati, C; Fuglei, E; Wiig, O; Derocher, A E

    2000-05-15

    This study was undertaken to test the symmetry of 2,3-diphosphoglycerate (2,3-DPG) binding site in hemoglobin (Hb). From Arnone's study [A. Arnone, Nature (London) 237 (1972) 146] the 2,3-DPG binding site is located at the top of the cavity, that runs through the center of the deoxy-Hb molecule. However, it is possible that this symmetry reported by Arnone, for crystals of 2,3-DPG-Hb complex, might not be conserved in solution. In this paper, we report the 31P nuclear magnetic resonances of the 2,3-DPG interaction with Hb. The 2,3-DPG chemical shifts of the P2 and P3 resonance are both pH- and hemoglobin-dependent [protein from man, polar bear (Ursus maritimus), Arctic fox (Alopex lagopus) and bovine]. 2,3-DPG binds tightly to deoxyhemoglobin and weakly, nevertheless significantly, to oxyhemoglobin. In particular, our results suggest similar spatial position of the binding site of 2,3-DPG in both forms of Hb in solutions. However, the most unexpected result was the apparent loss of symmetry in the binding site, which might correlate with the ability of the hemoglobin to modulate its functional behavior. The different interactions of the phosphate groups indicate small differences in the quaternary structure of the different deoxy forms of hemoglobin. Given the above structural perturbation an asymmetric binding in the complex could justify, at least in part, different physiological properties of Hb. Regardless, functionally relevant effects of 2,3-DPG seem to be measured and best elucidated through solution studies.

  6. Decontamination and decommissioning of the MTR-603 HB-2 cubicle

    International Nuclear Information System (INIS)

    Smith, D.L.

    1987-01-01

    The decontamination and decommissioning (D and D) of the MTR-603 HB-2 cubicle located at the Idaho National Engineering Laboratory (INEL) are described. The HP-2 cubicle became radioactively contaminated during out-of-pile circulating water loop experiments conducted in the Materials Testing Reactor in the 1950s and 1960s. The work performed to accomplish the D and D objectives of reducing the high radiation fields caused by contamination inside the cubicle, preventing future contamination spread, and making about 1400 ft 2 of floor space available for reuse are discussed. Decommissioning of the HB-2 cubicle consisted of total dismantlement of the cubicle and its contents and was performed without disrupting ongoing laboratory work being conducted in areas surrounding the HB-2 cubicle

  7. Hb H disease resulting from the association of an αº-thalassemia allele [-(α20.5] with an unstable α-globin variant [Hb Icaria]: first report on the occurrence in Brazil

    Directory of Open Access Journals (Sweden)

    Elza M. Kimura

    2009-01-01

    Full Text Available Hb H Disease is caused by the loss or inactivation of three of the four functional a-globin genes. Patients present chronic hemolytic anemia and splenomegaly. In some cases, occasional blood transfusions are required. Deletions are the main cause of this type of thalassemia (α-thalassemia. We describe here an unusual case of Hb H disease caused by the combination of a common αº deletion [-(α20.5] with a rare point mutation (c.427T > A, thus resulting in an elongated and unstable α-globin variant, Hb Icaria, (X142K, with 31 additional amino-acid residues. Very high levels of Hb H and Hb Bart's were detected in the patient's red blood cells (14.7 and 19.0%, respectively. This is the first description of this infrequent association in the Brazilian population.

  8. Cloning, expression, purification, crystallization and preliminary X-ray crystallographic study of molybdopterin synthase from Thermus thermophilus HB8

    International Nuclear Information System (INIS)

    Kanaujia, Shankar Prasad; Ranjani, Chellamuthu Vasuki; Jeyakanthan, Jeyaraman; Ohmori, Miwa; Agari, Kazuko; Kitamura, Yoshiaki; Baba, Seiki; Ebihara, Akio; Shinkai, Akeo; Kuramitsu, Seiki; Shiro, Yoshitsugu; Sekar, Kanagaraj; Yokoyama, Shigeyuki

    2007-01-01

    The molybdopterin synthase from T. thermophilus HB8 was cloned, expressed, purified and crystallized. The crystals belong to space group P2 1 and diffracted to a resolution of 1.64 Å. Thermus thermophilus is a Gram-negative aerobic thermophilic eubacterium which can grow at temperatures ranging from 323 to 355 K. In addition to their importance in thermostability or adaptation strategies for survival at high temperatures, the thermostable enzymes in thermophilic organisms contribute to a wide range of biotechnological applications. The molybdenum cofactor in all three kingdoms consists of a tricyclic pyranopterin termed molybdopterin that bears the cis-dithiolene group responsible for molybdenum ligation. The crystals of molybdopterin synthase from T. thermophilus HB8 belong to the primitive monoclinic space group P2 1 , with unit-cell parameters a = 33.94, b = 103.32, c = 59.59 Å, β = 101.3°. Preliminary studies and molecular-replacement calculations reveal the presence of three monomers in the asymmetric unit

  9. Prevalência de hemoglobinas anormais em recém-nascidos da cidade de Natal, Rio Grande do Norte, Brasil

    Directory of Open Access Journals (Sweden)

    Araújo Maria Cristina Pignataro Emerenciano de

    2004-01-01

    Full Text Available As hemoglobinopatias estão incluídas dentre as doenças hereditárias mais freqüentes nas populações humanas. Estudos realizados em diferentes regiões do Brasil têm demonstrado que as hemoglobinas anormais S e C são as mais prevalentes. Com o objetivo de investigar a prevalência de hemoglobinas anormais no período neonatal, foram analisadas 1.940 amostras de sangue de cordão umbilical provenientes de recém-nascidos de três maternidades da cidade de Natal, Rio Grande do Norte. Todas as amostras foram submetidas à eletroforese de hemoglobina em acetato de celulose utilizando tampão Tris-EDTA-Borato pH 8,5. As amostras que apresentaram hemoglobinas anormais foram submetidas à eletroforese em gel de ágar pH 6,2 para confirmação. Foram identificadas 37 (1,91% amostras com hemoglobinas anormais, das quais 29 (1,50% com traço falciforme (Hb FAS, 06 (0,31 % com Hb C, uma (0,05 % com anemia falciforme (Hb FS e uma (0,05 % apresentou Hb Bart's, sugerindo alfa talassemia. Os resultados encontrados evidenciam a necessidade de implantação da triagem de hemoglobinopatias em recém-nascidos na nossa população.

  10. Isolation and characterization of atrazine mineralizing Bacillus subtilis strain HB-6.

    Directory of Open Access Journals (Sweden)

    Jinhua Wang

    Full Text Available Atrazine is a widely used herbicide with great environmental concern due to its high potential to contaminate soil and waters. An atrazine-degrading bacterial strain HB-6 was isolated from industrial wastewater and the 16S rRNA gene sequencing identified HB-6 as a Bacillus subtilis. PCR assays indicated that HB-6 contained atrazine-degrading genes trzN, atzB and atzC. The strain HB-6 was capable of utilizing atrazine and cyanuric acid as a sole nitrogen source for growth and even cleaved the s-triazine ring and mineralized atrazine. The strain demonstrated a very high efficiency of atrazine biodegradation with a broad optimum pH and temperature ranges and could be enhanced by cooperating with other bacteria, suggesting its huge potential for remediation of atrazine-contaminated sites. To our knowledge, there are few Bacillus subtilis strains reported that can mineralize atrazine, therefore, the present work might provide some new insights on atrazine remediation.

  11. HbA2 measurements in β-thalassemia and in other conditions

    Directory of Open Access Journals (Sweden)

    Giovanni Ivaldi

    2014-09-01

    Full Text Available Quite a few papers have been written on the significance of elevated hemoglobin (Hb A2 as a parameter for the diagnosis of β-thalassemia trait, on the cutoff values to be used in diagnostics and on the significance and effects of factors reducing or elevating the expression of HbA2 and last but not least on the need for reliable measurement methods and precise calibrations with accurate standards. However, little has been published on the causes that elevate or reduce the HbA2 levels in β- and a-thalassemia and in other conditions. For a better understanding of the value of a precise measurement of this parameter we summarize and elucidate in this review the direct and indirect mechanisms that cause the variations in HbA2 expression and that influence the value of this parameter in particular conditions. We conclude by explaining the advantages and disadvantages of trusting on a precise measurement in the complete diagnostic contest.

  12. Molecular Controls of the Oxygenation and Redox Reactions of Hemoglobin

    Science.gov (United States)

    Henkens, Robert; Alayash, Abdu I.; Banerjee, Sambuddha; Crumbliss, Alvin L.

    2013-01-01

    Abstract Significance: The broad classes of O2-binding proteins known as hemoglobins (Hbs) carry out oxygenation and redox functions that allow organisms with significantly different physiological demands to exist in a wide range of environments. This is aided by allosteric controls that modulate the protein's redox reactions as well as its O2-binding functions. Recent Advances: The controls of Hb's redox reactions can differ appreciably from the molecular controls for Hb oxygenation and come into play in elegant mechanisms for dealing with nitrosative stress, in the malarial resistance conferred by sickle cell Hb, and in the as-yet unsuccessful designs for safe and effective blood substitutes. Critical Issues: An important basic principle in consideration of Hb's redox reactions is the distinction between kinetic and thermodynamic reaction control. Clarification of these modes of control is critical to gaining an increased understanding of Hb-mediated oxidative processes and oxidative toxicity in vivo. Future Directions: This review addresses emerging concepts and some unresolved questions regarding the interplay between the oxygenation and oxidation reactions of structurally diverse Hbs, both within red blood cells and under acellular conditions. Developing methods that control Hb-mediated oxidative toxicity will be critical to the future development of Hb-based blood substitutes. Antioxid. Redox Signal. 18, 2298–2313. PMID:23198874

  13. The changing relationship between HbA1c and FPG according to different FPG ranges.

    Science.gov (United States)

    Guan, X; Zheng, L; Sun, G; Guo, X; Li, Y; Song, H; Tian, F; Sun, Y

    2016-05-01

    Since the American Diabetes Association included hemoglobin A1c (HbA1c) in the diagnostic criteria for diabetes in 2010, the clinical use of HbA1c has remained controversial. We explored the use of HbA1c for diagnosing diabetes and intermediate hyperglycemia in comparison with fasting plasma glucose (FPG). We screened 3710 adult subjects (mean age = 55.24 years) comprising 1704 males and 2006 females. We drew an receiver operating characteristic (ROC) curve to evaluate the ability of HbA1c to diagnose diabetes and intermediate hyperglycemia according to FPG. We used Kappa coefficient and Pearson's correlation coefficient to evaluate the relationship between HbA1c and FPG in different FPG ranges. The areas under ROC curve to diagnose diabetes and intermediate hyperglycemia were 0.859 (95 % CI 0.827-0.892) and 0.633 (95 % CI 0.615-0.651). The kappa coefficients between FPG and HbA1c for diagnosis of diabetes and intermediate hyperglycemia were 0.601 (P HbA1c was 0.640 (P HbA1c and FPG changed according to the different FPG ranges. When FPG was higher, the relationship was stronger. HbA1c and FPG were highly consistent in diagnosing diabetes, but they were not in predicting intermediate hyperglycemia.

  14. Molecular basis of structural makeup of hulless barley in relation to rumen degradation kinetics and intestinal availability in dairy cattle: A novel approach.

    Science.gov (United States)

    Damiran, D; Yu, P

    2011-10-01

    To date, no study has been done of molecular structures in relation to nutrient degradation kinetics and intestinal availability in dairy cattle. The objectives of this study were to (1) reveal molecular structures of hulless barley affected by structural alteration using molecular spectroscopy (diffuse reflectance infrared Fourier transform) as a novel approach, and (2) quantify structure features on a molecular basis in relation to digestive kinetics and nutritive value in the rumen and intestine in cattle. The modeled feeds in this study were 4 types of hulless barley (HB) cultivars modified in starch traits: (a) normal starch cultivar, (b) zero-amylose waxy, (c) waxy, and (d) high-amylose. The molecular structural features were determined using diffuse reflectance infrared Fourier transform spectroscopy in the mid-infrared region (ca. 4,000-800 cm(-1)) of the electromagnetic spectrum. The items assessed included infrared intensity attributed to protein amide I (ca. 1,715-1,575 cm(-1)), amide II (ca. 1,575-1,490 cm(-1)), α-helix (ca. 1,648-1,660 cm(-1)), β-sheet (ca. 1,625-1,640 cm(-1)), and their ratio, β-glucan (ca. 1,445-1,400 cm(-1)), total carbohydrates (CHO; ca. 1,188-820 cm(-1)) and their 3 major peaks, structural carbohydrates (ca. 1,277-1,190 cm(-1)), and ratios of amide I to II and amide I to CHO. The results show that (1) the zero-amylose waxy was the greatest in amide I and II peak areas, as well as in the ratio of protein amide I to CHO among HB; (2) α-helix-to-β-sheet ratio differed among HB: the high-amylose was the greatest, the zero-amylose waxy and waxy were the intermediate, and the normal starch was the lowest; (3) HB were similar in β-glucan and CHO molecular structural makeup; (4) altered starch HB cultivars were similar to each other, but were different from the normal starch cultivar in protein molecular makeup; and (5) the rate and extent of rumen degradation of starch and protein were highly related to the molecular structural

  15. Hb and dyslipidaemia as predicting markers of serum alanine aminotransferase elevation in Chinese adolescents.

    Science.gov (United States)

    Chao, Kuo-Ching; Chang, Chun-Chao; Owaga, Eddy; Bai, Chyi-Huey; Huang, Tzu-chieh; Pan, Wen-Harn; Chang, Jung-Su

    2016-04-01

    Fe is an essential element for erythropoiesis and Hb synthesis. High Hb levels affect the blood's viscosity and are associated with cardiovascular dysfunction. The aim of the present study was to examine relationships of Hb and cardiometabolic abnormalities with the risk of alanine aminotransferase (ALT) elevation in adolescents. A population-based, cross-sectional study. National Nutrition and Health Survey in Taiwan (2010-2011, adolescents). Healthy adolescents aged 13-18 years. In total, 1941 adolescents (963 boys and 978 girls) were entered in the study. The mean age was 15·3 (sd 0·1) years (boys, 15·3 (sd 0·1) years; girls, 15·2 (sd 0·1) years). ALT tertile cut-off points for boys were 11 and 16 U/l, and for girls were 9 and 12 U/l. Girls without dyslipidaemia and presenting in the highest quartile (Q1) of Hb (>13·6 g/dl) were 1·89 and 3·76 times more likely to have raised serum ALT (9 and >12 U/l, respectively) than the reference (lowest quartile of Hb (Q1), 12 U/l) than the reference (Q1 of Hb, 15·4 g/dl), who were 7·40 times more likely to have elevated serum ALT of >16 U/l than the reference (Q1 of Hb, Hb level is a predictor of elevated serum ALT in adolescent girls with dyslipidaemia. Our study also highlights the importance of further research to establish cut-off points for Hb and its utility in diagnosing and preventing the onset of dyslipidaemia in adolescents.

  16. HbA1c as a predictor of diabetes after gestational diabetes mellitus.

    Science.gov (United States)

    Claesson, Rickard; Ignell, Claes; Shaat, Nael; Berntorp, Kerstin

    2017-02-01

    We wanted to investigate third-trimester HbA1c as a predictor of diabetes after gestational diabetes mellitus (GDM). Women with GDM were followed up prospectively for five years from pregnancy to detect the development of diabetes. The ability of HbA1c to predict diabetes was evaluated with receiver-operating characteristic (ROC) curves and logistic regression analysis. By five years, 73 of 196 women had been diagnosed with diabetes. An optimal cut-off point for HbA1c of 36mmol/mol (5.4%) could predict diabetes with 45% sensitivity and 92% specificity. For HbA1c ≥39mmol/mol (≥5.7%), sensitivity, specificity, and positive predictive value were 30%, 97%, and 91%, respectively. In logistic regression analysis, adjusting for the diagnostic glucose concentration during pregnancy, HbA1c levels in the upper quartile (≥36mmol/mol) were associated with a 5.5-fold increased risk of diabetes. Third-trimester HbA1c levels in the pre-diabetes range revealed women with post-partum diabetes with high specificity and high positive predictive value. HbA1c testing could be used as a strategy to select high-risk women for lifestyle interventions aimed at prevention of diabetes starting during pregnancy. The results should encourage further validation in other populations using new diagnostic criteria for GDM. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  17. TGFβ induces proHB-EGF shedding and EGFR transactivation through ADAM activation in gastric cancer cells

    International Nuclear Information System (INIS)

    Ebi, Masahide; Kataoka, Hiromi; Shimura, Takaya; Kubota, Eiji; Hirata, Yoshikazu; Mizushima, Takashi; Mizoshita, Tsutomu; Tanaka, Mamoru; Mabuchi, Motoshi; Tsukamoto, Hironobu; Tanida, Satoshi; Kamiya, Takeshi; Higashiyama, Shigeki; Joh, Takashi

    2010-01-01

    Research highlights: → TGFβ induces EGFR transactivation through proHB-EGF shedding by activated ADAM members in gastric cancer cells. → TGFβ induces nuclear translocation of HB-EGF-CTF cleaved by ADAM members. → TGFβ enhances cell growth by EGFR transactivation and HB-EGF-CTF nuclear translocation and ADAM inhibitors block these effects. → Silencing of ADAM17 also blocks EGFR transactivation, HB-EGF-CTF nuclear translocation and cancer cell growth by TGFβ. → ADAM17 may play a crucial role in this TGFβ-HB-EGF signal transduction. -- Abstract: Background and aims: Transforming growth factor-beta (TGFβ) is known to potently inhibit cell growth. Loss of responsiveness to TGFβ inhibition on cell growth is a hallmark of many types of cancer, yet its mechanism is not fully understood. Membrane-anchored heparin-binding EGF-like growth factor (proHB-EGF) ectodomain is cleaved by a disintegrin and metalloproteinase (ADAM) members and is implicated in epidermal growth factor receptor (EGFR) transactivation. Recently, nuclear translocation of the C-terminal fragment (CTF) of pro-HB-EGF was found to induce cell growth. We investigated the association between TGFβ and HB-EGF signal transduction via ADAM activation. Materials and methods: The CCK-8 assay in two gastric cancer cell lines was used to determine the effect for cell growth by TGFβ. The effect of two ADAM inhibitors was also evaluated. Induction of EGFR phosphorylation by TGFβ was analyzed and the effect of the ADAM inhibitors was also examined. Nuclear translocation of HB-EGF-CTF by shedding through ADAM activated by TGFβ was also analyzed. EGFR transactivation, HB-EGF-CTF nuclear translocation, and cell growth were examined under the condition of ADAM17 knockdown. Result: TGFβ-induced EGFR phosphorylation of which ADAM inhibitors were able to inhibit. TGFβ induced shedding of proHB-EGF allowing HB-EGF-CTF to translocate to the nucleus. ADAM inhibitors blocked this nuclear translocation. TGF

  18. Spinal Hb9::Cre-derived excitatory interneurons contribute to rhythm generation in the mouse.

    Science.gov (United States)

    Caldeira, Vanessa; Dougherty, Kimberly J; Borgius, Lotta; Kiehn, Ole

    2017-01-27

    Rhythm generating neurons are thought to be ipsilaterally-projecting excitatory neurons in the thoracolumbar mammalian spinal cord. Recently, a subset of Shox2 interneurons (Shox2 non-V2a INs) was found to fulfill these criteria and make up a fraction of the rhythm-generating population. Here we use Hb9::Cre mice to genetically manipulate Hb9::Cre-derived excitatory interneurons (INs) in order to determine the role of these INs in rhythm generation. We demonstrate that this line captures a consistent population of spinal INs which is mixed with respect to neurotransmitter phenotype and progenitor domain, but does not overlap with the Shox2 non-V2a population. We also show that Hb9::Cre-derived INs include the comparatively small medial population of INs which continues to express Hb9 postnatally. When excitatory neurotransmission is selectively blocked by deleting Vglut2 from Hb9::Cre-derived INs, there is no difference in left-right and/or flexor-extensor phasing between these cords and controls, suggesting that excitatory Hb9::Cre-derived INs do not affect pattern generation. In contrast, the frequencies of locomotor activity are significantly lower in cords from Hb9::Cre-Vglut2 Δ/Δ mice than in cords from controls. Collectively, our findings indicate that excitatory Hb9::Cre-derived INs constitute a distinct population of neurons that participates in the rhythm generating kernel for spinal locomotion.

  19. Identification of diphtheria toxin R domain mutants with enhanced inhibitory activity against HB-EGF.

    Science.gov (United States)

    Suzuki, Keisuke; Mizushima, Hiroto; Abe, Hiroyuki; Iwamoto, Ryo; Nakamura, Haruki; Mekada, Eisuke

    2015-05-01

    Heparin-binding epidermal growth factor-like growth factor (HB-EGF), a ligand of EGF receptor, is involved in the growth and malignant progression of cancers. Cross-reacting material 197, CRM197, a non-toxic mutant of diphtheria toxin (DT), specifically binds to the EGF-like domain of HB-EGF and inhibits its mitogenic activity, thus CRM197 is currently under evaluation in clinical trials for cancer therapy. To develop more potent DT mutants than CRM197, we screened various mutant proteins of R domain of DT, the binding site for HB-EGF. A variety of R-domain mutant proteins fused with maltose-binding protein were produced and their inhibitory activity was evaluated in vitro. We found four R domain mutants that showed much higher inhibitory activity against HB-EGF than wild-type (WT) R domain. These R domain mutants suppressed HB-EGF-dependent cell proliferation more effectively than WT R domain. Surface plasmon resonance revealed their higher affinity to HB-EGF than WT R domain. CRM197(R460H) carrying the newly identified mutation showed increased cell proliferation inhibitory activity and affinity to HB-EGF. These results suggest that CRM197(R460H) or other recombinant proteins carrying newly identified mutation(s) in the R domain are potential therapeutics targeting HB-EGF. © The Authors 2014. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.

  20. Registration of a High Yielding Malt Barley Variety HB1454 for the ...

    African Journals Online (AJOL)

    else

    Bayeh and Berhane 2011). Even though Ethiopia has favorable environment and .... malting profile for HB1454 is better than Beka for kernel weight, plump kernels, hectoliter weight and grain protein. HB1454 has shown relatively low percentage.

  1. To establish trimester-specific reference ranges for glycated haemoglobin (HbA1c) in pregnancy

    LENUS (Irish Health Repository)

    O'Connor, CM

    2011-09-01

    Background and aims: Diabetes in Pregnancy imposes additional risks to both mother and infant. These poor outcomes are considered to be primarily related to glycaemic control which is monitored longitudinally through pregnancy by means of HbA1c. The correlation between HbA1c levels with clinical outcomes emphasises the need to measure HbA1c accurately, precisely and for data interpretation comparison to appropriately defined reference intervals. From July 1st 2010, the HbA1c assay in Irish laboratories became fully metrologically traceable to the IFCC standard, permitting HbA1c to be reported in IFCC units (mmol\\/mol) and derived DCCT\\/NGSP units (%) using the IFCC-DCCT\\/NGSP master equation (DCCT = Diabetes Control and Complications Trial, NGSP = National Glycohemoglobin standardisation program). The aim of this project is to establish trimester-specific reference ranges in pregnancy for IFCC standardised HbA1c in non-diabetic Caucasian women. This will allow us to define the goal for HbA1c during pregnancy complicated by diabetes.\\r\

  2. Studying the interaction between three synthesized heterocyclic sulfonamide compounds with hemoglobin by spectroscopy and molecular modeling techniques.

    Science.gov (United States)

    Naeeminejad, Samane; Assaran Darban, Reza; Beigoli, Sima; Saberi, Mohammad Reza; Chamani, Jamshidkhan

    2017-11-01

    The interaction between synthesized heterocyclic benzene sulfonamide compounds, N-(7-benzyl-56-biphenyl-2m-tolyl-7H-pyrrolo[23-d]pyrimidine-4-yl)-benzene sulfonamide (HBS 1 ), N-(7-benzyl-56-biphenyl-2-m-tolyl-7H-pyrrolo[23-d] pyrimidine-4-yl)-4-methyl- benzene sulfonamide (HBS 2 ), and N-(7-benzyl-56-biphenyl-2-m-tolyl-7H-pyrrolo[23-d]pyrimidine-4-yl)-4-chloro-benzene sulfonamide (HBS 3 ) with Hb was studied by fluorescence quenching, zeta potentional, circular dichroism, and molecular modeling techniques. The fluorescence spectroscopy experiments were performed in order to study the conformational changes, possibly due to a discrete reorganization of Trp residues during binding between HBS derivatives and Hb. The variation of the K SV value suggested that hydrophobic and electrostatic interactions were the predominant intermolecular forces stabilizing the complex. The K SV1 ans K SV2 values of HBS derivatives with Hb are .6 × 10 13 and 3 × 10 13  M -1 for Hb-HBS 1 , 1 × 10 13 and 4 × 10 13  M -1 for Hb-HBS 2 , .9 × 10 13 , and 6 × 10 13  M -1 for Hb-HBS 3 , respectively. The molecular distances between Hb and HBS derivatives in binary and ternary systems were estimated according to Förster's theory of dipole-dipole non-radiation energy transfer. The quantitative analysis data of circular dichroism spectra demonstrated that the binding of the three HBS derivatives to Hb induced conformational changes in Hb. Changes in the zeta potential of the Hb-HBS derivatives complexes demonstrated a hydrophobic adsorption of the anionic ligand onto the surface of Hb as well as both electrostatic and hydrophobic adsorption in the case of the complex. The modeling data thus confirmed the experimental results. This study is expected to provide important insight into the interaction of Hb with three HBS derivatives to use in various toxicological and therapeutic processes.

  3. Effects of a healthier snack on snacking habits and glycated Hb (HbA1c): a 6-week intervention study.

    Science.gov (United States)

    Yan, Mary R; Parsons, Andrew; Whalley, Gillian A; Rush, Elaine C

    2016-12-01

    Dietary behaviour modification may change eating habits and reduce the impact of poor nutrition. This study aimed to evaluate the effects of daily consumption of a healthier snack bar on snacking habits and glycated Hb (HbA1c) within a 6-week intervention. In all, twenty-eight participants were randomly allocated to two groups to either consume the bars as the main snack for 6 weeks (n 14) or receipt of the bars was delayed for 6 weeks (n 14) following a stepped-wedge design. All participants had HbA1c concentrations measured at weeks -1, 0, 4, 6, 10 and 12. A short dietary habits questionnaire was self-completed at weeks 0, 6 and 12. Participants consumed the bars they received instead of other snacks, and found that the healthier snack bar was acceptable as part of their daily dietary pattern. Over the 12 weeks, there was a significant reduction in intake of biscuits, cakes and pies (approximately 2 servings/week, Psnack intervention and a trend towards a favourable effect on glucose homoeostasis. Habitual snacking behaviour has the potential to be improved through changes in the food supply, and in the longer term may reduce the impact of poor nutrition on public health.

  4. Hb A1c Separation by High Performance Liquid Chromatography in Hemoglobinopathies

    OpenAIRE

    Chandrashekar, Vani

    2016-01-01

    Hb A1c measurement is subject to interference by hemoglobin traits and this is dependent on the method used for determination. In this paper we studied the difference between Hb A1c measured by HPLC in hemoglobin traits and normal chromatograms. We also studied the correlation of Hb A1c with age. Hemoglobin analysis was carried out by high performance liquid chromatography. Spearman's rank correlation was used to study correlation between A1c levels and age. Mann-Whitney U test was used to st...

  5. Hereditary Persistence of Fetal Hemoglobin Caused by Single Nucleotide Promoter Mutations in Sickle Cell Trait and Hb SC Disease.

    Science.gov (United States)

    Akinbami, Anthony O; Campbell, Andrew D; Han, Zeqiu J; Luo, Hong-Yuan; Chui, David H K; Steinberg, Martin H

    2016-01-01

    Hereditary persistence of fetal hemoglobin (HPFH) can be caused by point mutations in the γ-globin gene promoters. We report three rare cases: a child compound heterozygous for Hb S (HBB: c.20A > T) and HPFH with a novel point mutation in the (A)γ-globin gene promoter who had 42.0% Hb S, 17.0% Hb A and 38.0% Hb F; a man with Hb SC (HBB: c.19G > A) disease and a point mutation in the (G)γ-globin gene promoter who had 54.0% Hb S, 18.0% Hb C and 25.0% Hb F; a child heterozygous for Hb S and HPFH due to mutations in both the (A)γ- and (G)γ-globin gene promoters in cis [(G)γ(A)γ(β(+)) HPFH], with 67.0% Hb A, 6.5% Hb S and 25.0% Hb F.

  6. Hemoglobin A1c (HbA1c) Test: MedlinePlus Lab Test Information

    Science.gov (United States)

    ... page: https://medlineplus.gov/labtests/hemoglobina1chba1ctest.html Hemoglobin A1c (HbA1c) Test To use the sharing features on this page, please enable JavaScript. What is a hemoglobin A1c (HbA1c) test? A hemoglobin A1c (HbA1c) test measures ...

  7. Evidência molecular da ocorrência de um fitoplasma associado ao lenho mole da macieira Molecular evidence for an association of a phytoplasma with apple rubbery wood

    Directory of Open Access Journals (Sweden)

    Luiz Fernando Caldeira Ribeiro

    2007-03-01

    Full Text Available O lenho mole da macieira é uma doença relevante em diversas partes do mundo. Sintomas típicos desta doença têm sido observados em pomares instalados em estados do sul do território brasileiro desde a década de oitenta. Enxertia tem revelado a natureza infecciosa da doença e a observação de corpúsculos filamentosos no floema tem evidenciado possível associação com fitoplasma. No presente trabalho plantas com sintomas de lenho mole foram coletadas em pomar comercial, visando demonstrar a presença de fitoplasma em tecido doente, bem como identificar molecularmente este fitoplasma. Através do emprego de duplo PCR com iniciadores universais R16mF2/R1 e R16F2n/R2, fitoplasma foi consistentemente detectado em plantas sintomáticas. A identificação conduzida com duplo PCR usando-se iniciadores específicos R16(IIIF2/R demonstrou que o fitoplasma detectado pertencia ao grupo 16SrIII. Análises de RFLP conduzidas com as endonucleases AluI, KpnI, HinfI, HpaII, MseI, RsaI e SauIIIA confirmaram que o fitoplasma era um representante típico do grupo 16SrIII. A detecção e identificação molecular se constitui numa forte evidência que um fitoplasma está associado ao lenho mole da macieira no Brasil, complementando os trabalhos realizados anteriormente com transmissão por enxertia e observação por microscopia eletrônica .Apple rubbery wood is an important disease occurring worldwide. Typical symptoms have been observed since 80' decade in orchards located in the South part of Brazil. In previous studies, grafting has evidenciated that the disease had infeccious etiology and visualization of filamentous bodies inside phloem had indicated that a phytoplasma could be associated with the disease. In the present study, plants with symptoms of rubbery wood were sampled in a commercial orchard in order to demonstrate the presence of phytoplasma in infected tissue and to identify molecularly that the organism. Using nested PCR with universal

  8. Elevated HbA1c and Fasting Plasma Glucose in Predicting Diabetes Incidence Among Older Adults

    Science.gov (United States)

    Lipska, Kasia J.; Inzucchi, Silvio E.; Van Ness, Peter H.; Gill, Thomas M.; Kanaya, Alka; Strotmeyer, Elsa S.; Koster, Annemarie; Johnson, Karen C.; Goodpaster, Bret H.; Harris, Tamara; De Rekeneire, Nathalie

    2013-01-01

    OBJECTIVE To determine which measures—impaired fasting glucose (IFG), elevated HbA1c, or both—best predict incident diabetes in older adults. RESEARCH DESIGN AND METHODS From the Health, Aging, and Body Composition study, we selected individuals without diabetes, and we defined IFG (100–125 mg/dL) and elevated HbA1c (5.7–6.4%) per American Diabetes Association guidelines. Incident diabetes was based on self-report, use of antihyperglycemic medicines, or HbA1c ≥6.5% during 7 years of follow-up. Logistic regression analyses were adjusted for age, sex, race, site, BMI, smoking, blood pressure, and physical activity. Discrimination and calibration were assessed for models with IFG and with both IFG and elevated HbA1c. RESULTS Among 1,690 adults (mean age 76.5, 46% men, 32% black), 183 (10.8%) developed diabetes over 7 years. Adjusted odds ratios of diabetes were 6.2 (95% CI 4.4–8.8) in those with IFG (versus those with fasting plasma glucose [FPG] HbA1c (versus those with HbA1c HbA1c were considered together, odds ratios were 3.5 (1.9–6.3) in those with IFG only, 8.0 (4.8–13.2) in those with elevated HbA1c only, and 26.2 (16.3–42.1) in those with both IFG and elevated HbA1c (versus those with normal FPG and HbA1c). Addition of elevated HbA1c to the model with IFG resulted in improved discrimination and calibration. CONCLUSIONS Older adults with both IFG and elevated HbA1c have a substantially increased odds of developing diabetes over 7 years. Combined screening with FPG and HbA1c may identify older adults at very high risk for diabetes. PMID:24135387

  9. Detection of the Unstable Hb Köln (HBB: c.295G>A) by a Capillary Electrophoresis Method.

    Science.gov (United States)

    Li, You-Qiong; Ye, Li-Hua; Mo, Yun

    2016-11-01

    Hb Köln (HBB: c.295G>A) is an unstable β-globin gene variant with a GTG>ATG substitution at codon 98. This variant is quite frequent in Europe and the USA but rare in China. It can easily be misdiagnosed as Hb Constant Spring (Hb CS; HBA2: c.427T>C) by high performance liquid chromatography (HPLC), but detection and quantification of both Hb Köln and degraded Hb Köln by capillary electrophoresis (CE) are possible. Thus, we concluded that CE was the preferred method for Hb Köln detection.

  10. Changing from glucose to HbA1c for diabetes diagnosis

    DEFF Research Database (Denmark)

    Nielsen, Aneta Aleksandra; Petersen, Per Hyltoft; Green, Anders

    2014-01-01

    BACKGROUND: In Denmark, the use of HbA1c in the diagnosis of diabetes was adopted from March 2012. We evaluated the change in the number of diabetes cases diagnosed by haemoglobin A1c (HbA1c) versus fasting venous plasma glucose (FPG), and estimated the influence of analytical variation and bias ...

  11. Antibacterial activity of a modified unfilled resin containing a novel polymerizable quaternary ammonium salt MAE-HB.

    Science.gov (United States)

    Huang, Li; Yu, Fan; Sun, Xiang; Dong, Yan; Lin, Ping-Ting; Yu, Hao-Han; Xiao, Yu-Hong; Chai, Zhi-Guo; Xing, Xiao-Dong; Chen, Ji-Hua

    2016-09-23

    Resins with strong and long-lasting antibacterial properties are critical for the prevention of secondary dental caries. In this study, we evaluated the antibacterial effect and the underlying mechanism of action of an unfilled resin incorporating 2-methacryloxylethyl hexadecyl methyl ammonium bromide (MAE-HB) against Streptococcus mutans UA159 (S. mutans UA159). MAE-HB was added into unfilled resin at 10 mass%, and unfilled resin without MAE-HB served as the control. Bacterial growth was inhibited on 10%-MAE-HB unfilled resin compared with the control at 1 d, 7 d, 30 d, or 180 d (P  0.05). No significant differences in the antibacterial activities of eluents from control versus 10%-MAE-HB unfilled resins were observed at any time point (P > 0.05). The number of bacteria attached to 10%-MAE-HB unfilled resin was considerably lower than that to control. Fe-SEM and CLSM showed that 10%-MAE-HB unfilled resin disturbed the integrity of bacterial cells. Expression of the bacterial glucosyltransferases, gtfB and gtfC, was lower on 10%-MAE-HB unfilled resin compared to that on control (P HB confers unfilled resin with strong and long-lasting antibacterial effects against S. mutans.

  12. Molecular Epidemiology of Hemoglobinopathies in Cambodia.

    Science.gov (United States)

    Munkongdee, Thongperm; Tanakulmas, Jatuporn; Butthep, Punnee; Winichagoon, Pranee; Main, Barbara; Yiannakis, Miriam; George, Joby; Devenish, Robyn; Fucharoen, Suthat; Svasti, Saovaros

    2016-06-01

    Determining the magnitude of the thalassemia problem in a country is important for implementing a national prevention and control program. In order to acquire accurate thalassemia prevalence data, the gene frequency of α- and β-thalassemia (α- and β-thal) in different regions of a country should be determined. The molecular basis of thalassemia in Cambodia was performed by polymerase chain reaction (PCR)-based techniques in a community-based cross-sectional survey of 1631 unrelated individuals from three regions, Battambang, Preah Vihear and Phnom Penh. Thalassemia mutations were detected in 62.7% of the three studied population of Cambodia. Hb E (HBB: c.79G > A) was the most common β-globin gene mutation with a frequency ranging from 0.139 to 0.331, while the most frequent α-globin gene mutation was the -α(3.7) (rightward) deletion (0.098-0.255). The other frequencies were 0.001-0.003 for β-thal, 0.008-0.011 for α-thal-1 (- -(SEA)), 0.003-0.008 for α-thal-2 [-α(4.2) (leftward deletion)], 0.021-0.044 for Hb Constant Spring (Hb CS, HBA2: c.427T > C) and 0.009-0.036 for Hb Paksé (HBA2: c.429A > T). A regional specific thalassemia gene frequency was observed. Preah Vihear had the highest prevalence of Hb E (55.9%), α-thal-2 (24.0%) and nondeletional α-thal (15.1%), whereas Phnom Penh had the lowest frequency of thalassemia genes. Interestingly, in Preah Vihear, the frequency of Hb Paksé was extremely high (0.036), almost equivalent to that of Hb CS (0.044). Our results indicate the importance of micromapping and epidemiology studies of thalassemia, which will assist in establishing the national prevention and control program in Cambodia.

  13. Changes in proHB-EGF expression after functional activation of the immune system cells

    Directory of Open Access Journals (Sweden)

    T. O. Chudina

    2017-12-01

    Full Text Available The level of proHB-EGF expression on J774, Raji, KG-1 cells derived from different types of human and mouse immune system cells under the standard in vitro culture conditions and during functional activation of these cells was investigated. Changes in the proHB-EGF expression on the cell surface were found to depend on the density of cell population, the content of fetal bovine serum in the culture medium, the effect of mitogenic factors – bacterial lipopolysaccharide, an inactive full-size form of diphtheria toxin (CRM197 and recombinant soluble HB-EGF – rsHB-EGF. The results obtained are important for the understanding of the functional role of proHB-EGF receptor on the surface of macrophage-like cells and B lymphocytes and indicate the involvement of this receptor in immune response regulation in an organism.

  14. Molecularly imprinted photo-sensitive polyglutamic acid nanoparticles for electrochemical sensing of hemoglobin

    International Nuclear Information System (INIS)

    Zhang, Rongli; Xu, Sheng; Luo, Jing; Liu, Xiaoya

    2015-01-01

    A voltammetric sensor for hemoglobin (Hb) was prepared from molecularly imprinted polymer nanoparticles (MINPs) via electrophoretic deposition. A photo-sensitive copolymer composed of poly-γ-glutamic grafted with the fluorophore 7-amino-4-methylcoumarin was converted into nanoparticles that were imprinted with Hb. The resultant MINPs were then placed on a glassy carbon electrode (GCE) via electrophoretic deposition. Subsequent photo-crosslinking locks the recognition sites. The template was removed by extraction with a mixture of acetic acid and methanol at a ratio of 1:9 (v:v) to obtain a voltammetric sensor for Hb. The current response of the sensor at a working voltage of −260 mV is linearly related to the concentration of Hb in the range from 5 to 100 μg mL −1 , and recoveries range from 98.7 to 102.3 %. Compared to the respective non-imprinted nanoparticles, the sensor displays high recognition capability and affinity for Hb. (author)

  15. Mild Microcytic Anemia in an Infant with a Compound Heterozygosity for Hb C (HBB: c.19G > A) and Hb Osu Christiansborg (HBB: c.157G > A).

    Science.gov (United States)

    Boucher, Maria O; Chui, David H K; Woda, Bruce A; Newburger, Peter E

    2016-06-01

    We report an infant with a compound heterozygosity for Hb C (HBB: c.19G > A) and Hb Osu Christiansborg (HBB: c.157G > A) and a phenotype of mild microcytic anemia with target cell morphology but without overt hemolysis.

  16. An alternative approach to modelling HbA1c trajectories in patients with type 2 diabetes mellitus.

    Science.gov (United States)

    McEwan, Phil; Bennett, Hayley; Qin, Lei; Bergenheim, Klas; Gordon, Jason; Evans, Marc

    2017-05-01

    Time-dependent HbA1c trajectories in health economic models of type 2 diabetes mellitus (T2DM) are typically informed by the UK Prospective Diabetes Study (UKPDS). However, this approach may not accurately predict HbA1c progression in patients who do not conform to the demographic profile of the original UKPDS cohort. This study aimed to develop an alternative mathematical model (MM) to simulate HbA1c progression in T2DM. A systematic literature review identified studies, published between 2005 and 2015, that reported HbA1c in adult T2DM patients over a minimum duration of 18 months. Pooled data from eligible studies were used to develop an alternative MM equation for HbA1c progression, which was then contrasted with the UKPDS 68 progression equation in illustrative scenarios. A total of 68 studies were eligible for data extraction (mean follow-up time 4.1 years). HbA1c progression was highly heterogeneous across studies, varying with baseline HbA1c, treatment group and patient age. The MM equation was fitted with parameters for mean baseline HbA1c (8.3%), initial change in HbA1c (-0.62%) and upper quartile of maximum observed HbA1c (9.3%). Differences in HbA1c trajectories between the MM and UKPDS approaches altered the timing of therapy escalation in illustrative scenarios. The MM represents an alternative approach to simulate HbA1c trajectories in T2DM models, as UKPDS data may not adequately reflect the heterogeneity of HbA1c profiles observed in clinical studies. However, the choice of approach should ultimately be determined by the characteristics of individual patients under consideration and the clinical face validity of the modelled trajectories. © 2016 John Wiley & Sons Ltd.

  17. NEAR-IR PHOTOMETRIC PROPERTIES OF HB, MSTO, AND SGB FOR METAL POOR GALACTIC GLOBULAR CLUSTERS

    Directory of Open Access Journals (Sweden)

    J.-W. Kim

    2007-03-01

    Full Text Available We report photometric features of the HB, MSTO, and SGB for a set of metal-poor Galactic globular clusters on the near-IR CMDs. The magnitude and color of the MSTO and SGB are measured on the fiducial normal points of the CMDs by applying a polynomial fit. The near-IR luminosity functions of horizontal branch stars in the classical second parameter pair M3 and M13 indicate that HB stars in M13 are dominated by hot stars that are rotatively faint in the infrared, whereas HB stars in M3 are brighter than those in M13. The luminosity functions of HB stars in the observed bulge clusters, except for NGC 6717, show a trend that the fainter hot HB stars are dominated in the relatively metal-poor clusters while the relatively metal-rich clusters contain the brighter HB stars. It is suggestive that NGC 6717 would be an extreme example of the second-parameter phenomenon for the bulge globular clusters.

  18. [Application of the polymerase chain reaction (PCR) in the diagnosis of Hb S-beta(+)-thalassemia].

    Science.gov (United States)

    Harano, K; Harano, T; Kushida, Y; Ueda, S

    1991-08-01

    Isoelectric focusing of the hemolysate prepared from a two-year-old American black boy with microcytic hypochromia showed the presence of a high percentage (63.3%) of such Hb variant as Hb S, while the levels of Hb A, Hb F and Hb A2 were 20.0%, 12.7%, and 4.0%, respectively. The ratio of the non-alpha-chain to the alpha-chain of the biosynthesized globin chains was 0.49. The variant was identified as Hb S by amino acid analysis of the abnormal peptide (beta T-1) and digestion of DNA amplified by the polymerase chain reaction with enzyme Eco 81 I. This was further confirmed by DNA sequencing. DNA sequencing of a beta-gene without the beta s-mutation revealed a nucleotide change of T to C in the polyadenylation signal sequence AATAAA 3' to the beta-gene, resulting in beta(+)-thalassemia. These results are consistent with the existence of a beta s-gene and a beta(+)-thalassemia gene in trans.

  19. Association of plasma PCB levels and HbA1c concentration in Iran.

    Science.gov (United States)

    Eftekhari, Sahar; Aminian, Omid; Moinfar, Zeinab; Schettgen, Thomas; Kaifie, Andrea; Felten, Michael; Kraus, Thomas; Esser, André

    2018-01-01

    The rapid increase in prevalence of diabetes mellitus over the last decades warrants more attention to the effects of environmental and occupational exposures on glucose metabolism. Our study aimed to assess the association between the plasma levels of various congeners of polychlorinated biphenyls (PCBs) and the serum concentration of glycated haemoglobin (HbA1c). Our study population consisted of 140 Iranian adults from seven different occupational groups and a group of non-occupationally exposed female participants. The plasma concentration of PCBs were determined at the laboratory of occupational toxicology at RWTH Aachen University, Germany. We considered an HbA1c concentration of 5.7% and more as indicating a disturbed glucose metabolism. Logistic regression was used to assess the association between quartiles of concentrations of PCB congeners and serum HbA1c. Participants with an increased HbA1c value had higher plasma levels of PCB 138, 153, 180 and the PCB sum, although this association was statistically not significant. There was no significant difference between the levels of PCB 138, 153, 180, the sum of these congeners, and PCB 118 in their quartiles when comparing with HbA1c concentrations. For our cohort, we could not demonstrate a significant association between PCB and HbA1c concentrations indicating a disturbance of glucose metabolism.

  20. HbA1c, systolic blood pressure variability and diabetic retinopathy in Asian type 2 diabetics.

    Science.gov (United States)

    Foo, Valencia; Quah, Joanne; Cheung, Gemmy; Tan, Ngiap Chun; Ma Zar, Kyi Lin; Chan, Choi Mun; Lamoureux, Ecosse; Tien Yin, Wong; Tan, Gavin; Sabanayagam, Charumathi

    2017-02-01

    The aim of the present study was to examine the association between variability in HbA1c or systolic blood pressure (SBP) and diabetes-specific moderate retinopathy in Asians with type 2 diabetes (T2D). A retrospective study was conducted of 172 cases of moderate diabetic retinopathy (DR) cases and 226 controls without DR, matched for age, sex, and ethnicity. Serial HbA1c and SBP (range 3-6 readings) over the 2 years prior to photographic screening of DR were collected. Intrapersonal mean and SD values for HbA1c (iM-HbA1c and iSD-HbA1c) and SBP (iM-SBP and iSD-SBP) were derived. Moderate DR was assessed from digital retinal photographs and defined as levels >43 using the Early Treatment Diabetic Retinopathy Study scale. Cases of moderate DR had higher iM-HbA1c (8.2 % vs 7.3 %; P = 0.001), iSD-HbA1c (1.22 vs 0.64; P = 0.001), iM-SBP (136.8 vs 129.6 mmHg; P = 0.001) and iSD-SBP (13.3 vs 11.1; P = 0.002) than controls. In the multivariate regression model adjusted for age, gender, ethnicity, duration of diabetes, SBP, and HbA1c, iM-HbA1c and iM-SBP were significantly associated with moderate DR (odds ratio [OR] 1.80, 95 % confidence interval [CI] 1.37-2.36; and OR 1.03, 95 % CI 1.01-1.05, respectively). Neither iSD-HbA1c nor iSD-SBP were associated with moderate DR. When stratified by HbA1c HbA1c levels and SBP, but not their variability, were associated with moderate DR. Among those with good glycemic control, wider variability of SBP is associated with moderate DR. © 2016 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.

  1. Analytical verification and quality assessment of the Tosoh HLC-723GX HbA1c analyzer

    Directory of Open Access Journals (Sweden)

    Marko Ris

    2017-04-01

    Full Text Available Objectives: Ion-exchange high-performance liquid chromatography (IE-HPLC has long been used as a reproducible and versatile analytical tool for HbA1c measurement.In this study, we performed analytical verification and quality assessment of the recently introduced small IE-HPLC Tosoh HLC-723GX HbA1c analyzer, and a comparison of results to immunoassay (IA and capillary electrophoresis (CE. Design and methods: The total imprecision of Tosoh HLC-723GX was verified according to CLSI EP15-A2 protocol using commercial control materials (C-QC and pooled human whole blood samples (HWB. The Sigma metric was used for the evaluation of quality targets. HbA1c results were compared to automated CE (MiniCap Flex Piercing, Sebia, France and IA (Tina-quant HbA1c Gen 2, Cobas Integra 400+, Roche Diagnostics, USA procedures. Results: The total imprecision of Tosoh HLC-723GX-HbA1c for IFCC(mmol/mol and NGSP(% units was: 1.91/1.25% (HbA1c=31 mmol/mol/5.0% and 0.51/0.63% (HbA1c=84 mmol/mol/9.8% for C-QC, and 0.39/0.2% (HbA1c=47 mmol/mol/6.5% and 0.77/0.46% (HbA1c=94 mmol/mol/10.8% in HWB samples, respectively. Bland-Altman analysis did not reveal any deviation of the results between Tosoh HLC-723GX and CE: mean difference 0.0% (95%CI: −0.02927 to 0.02653%, while the mean HbA1c difference against IA was −0.07% (95%CI: −0.1039 to −0.02765. At the selected HbA1c clinical decision level (48 mmol/mol/6,5%, six sigma analysis gave σ value of 3.91, within a desirable classification of performance. Conclusion: The analytical performance of the Tosoh HLC-723GX complies with the rigorous quality criteria for clinical use of HbA1c, with the results comparable to the CE procedure. Tosoh HLC-723GX provides a plausible analytical choice for reliable HbA1c measurement in low-volume laboratories. Keywords: HbA1c, Quality targets, Six sigma, Tosoh HLC-723GX analyzer

  2. HB-Line Dissolution of Glovebox Floor Sweepings

    International Nuclear Information System (INIS)

    Gray, J.H.

    1998-02-01

    Two candidate flowsheets for dissolving glovebox floor sweepings in the HB-Line Phase I geometrically favorable dissolver have been developed.Dissolving conditions tested and modified during the laboratory program were based on the current processing scheme for dissolving high-fired Pu-238 oxide in HB-Line. Subsequent adjustments made to the HB-Line flowsheet reflected differences in the dissolution behavior between high-fired Pu-238 oxide and the MgO sand/PuF 4 /PuO 2 mixture in glovebox floor sweepings. Although both candidate flowsheets involved two separate dissolving steps and resulted incomplete dissolution of all solids, the one selected for use in HB-Line will require fewer processing operations and resembles the initial flowsheet proposed for dissolving sand, slag, and crucible material in F-Canyon dissolvers. Complete dissolution of glovebox floor sweepings was accomplished in the laboratory by initially dissolving between 55 and 65 degree in a 14 molar nitric acid solution. Under these conditions, partial dissolution of PuF 4 and complete dissolution of PuO 2 and MgO sand were achieved in less than one hour. The presence of free fluoride in solution,uncomplexed by aluminum, was necessary for complete dissolution of the PuO 2 .The remaining PuF 4 dissolved following addition of aluminum nitrate nonahydrate (ANN) to complex the fluoride and heating between 75 and 85 degree C for an additional hour. Precipitation of magnesium and/or aluminum nitrates could occur before, during, and after transfer of product solutions. Both dilution and/or product solution temperature controls may be necessary to prevent precipitation of these salts. Corrosion of the dissolver should not be an issue during these dissolving operations. Corrosion is minimized when dissolving at 55-65 degree C for one to three hours at a maximum uncomplexed free fluoride concentration of 0.07 molar and by dissolving at 75-85 degree C at a one to one aluminum to fluoride mole ratio for another

  3. Association of fibrinogen with HbA1C in diabetic foot ulcer

    Science.gov (United States)

    Pase, M. A.; Gatot, D.; Lindarto, D.

    2018-03-01

    Fibrinogen is one of the inflammatory markers of vascular changes and endothelial dysfunction in diabetic patients. The aim of this study to associate serum fibrinogen levels with HbA1C in diabetic foot ulcer (DFU). This study was cross-sectional and retrospective in DFU patients from January to July 2017 in Haji Adam Malik Central General Hospital. The patients enrolled in the study were T2DM with DFU as a complication. The grading of DFU was evaluated according to the Wagner’s Classification. Serum fibrinogen level, HbA1C and ankle-brachial index (ABI) were carried out directly in the patients. Fibrinogen serum levels were found significantly with HbA1C (P=0.001, r=0.387) and ABI (P=0.008, r=-0.454). Fibrinogen serum levels in DFU patients were positively correlated with HbA1C and significantly higher in patients with poor glycemic control.

  4. Trajectories of HbA1c Levels in Children and Youth with Type 1 Diabetes

    Science.gov (United States)

    Pinhas-Hamiel, Orit; Hamiel, Uri; Boyko, Valentina; Graph-Barel, Chana; Reichman, Brian; Lerner-Geva, Liat

    2014-01-01

    Purpose To illustrate the distribution of Hemoglobin A1c (HbA1c) levels according to age and gender among children, adolescents and youth with type 1 diabetes (T1DM). Methods Consecutive HbA1c measurements of 349 patients, aged 2 to 30 years with T1DM were obtained from 1995 through 2010. Measurement from patients diagnosed with celiac disease (n = 20), eating disorders (n = 41) and hemoglobinopathy (n = 1) were excluded. The study sample comprised 4815 measurements of HbA1c from 287 patients. Regression percentiles of HbA1c were calculated as a function of age and gender by the quantile regression method using the SAS procedure QUANTREG. Results Crude percentiles of HbA1c as a function of age and gender, and the modeled curves produced using quantile regression showed good concordance. The curves show a decline in HbA1c levels from age 2 to 4 years at each percentile. Thereafter, there is a gradual increase during the prepubertal years with a peak at ages 12 to 14 years. HbA1c levels subsequently decline to the lowest values in the third decade. Curves of females and males followed closely, with females having HbA1c levels about 0.1% (1.1 mmol/mol) higher in the 25th 50th and 75th percentiles. Conclusion We constructed age-specific distribution curves for HbA1c levels for patients with T1DM. These percentiles may be used to demonstrate the individual patient's measurements longitudinally compared with age-matched patients. PMID:25275650

  5. Empirically establishing blood glucose targets to achieve HbA1c goals.

    Science.gov (United States)

    Wei, Nancy; Zheng, Hui; Nathan, David M

    2014-04-01

    OBJECTIVE To determine the average fasting, postprandial, and bedtime self-monitored blood glucose (SMBG) concentrations associated with specified HbA1c levels using data from the A1c-Derived Average Glucose (ADAG) study. RESEARCH DESIGN AND METHODS The ADAG study was a multicenter observational study that used continuous glucose monitoring and SMBG testing to determine the relationship between mean average glucose and HbA1c. We used the SMBG data from 470 of the ADAG study participants (237 with type 1 diabetes and 147 with type 2 diabetes) to determine the average fasting, premeal, 90-min postmeal, and bedtime blood glucose (BG) for predefined target HbA1c groups between 5.5 and 8.5% (37-69 mmol/mol). t Tests were used to compare mean BG values between type 1 and type 2 diabetes groups. RESULTS The average fasting BG needed to achieve predefined HbA1c target levels of 5.5-6.49% (37-47 mmol/mol), 6.5-6.99% (48-52 mmol/mol), 7.0-7.49% (52-58 mmol/mol), 7.5-7.99% (58-64 mmol/mol), and 8.0-8.5% (64-69 mmol/mol) were 122 mg/dL with 95% CI 117-127, 142 mg/dL (135-150), 152 mg/dL (143-162), 167 mg/dL (157-177), and 178 mg/dL (164-192), respectively. Postmeal BG to achieve the HbA1c level of 6.5-6.99% (48-52 mmol/mol) and 7.0-7.49% (52-58 mmol/mol) were 139 mg/dL (134-144) and 152 mg/dL (147-157), respectively. Bedtime BG was 153 mg/dL (145-161) and 177 mg/dL (166-188), respectively. CONCLUSIONS We have determined the average BG at premeal, postmeal, and bedtime to achieve a variety of HbA1c targets. These results, based on empirical data, will help patients and providers set realistic day-to-day SMBG targets to achieve individualized HbA1c goals.

  6. Decontamination and decommissioning of the MTR [Materials Testing Reactor]-603 HB-2 cubicle

    International Nuclear Information System (INIS)

    Smith, D.L.

    1987-10-01

    This paper describes the decontamination and decommissioning (D and D) of the MTR-603 HB-2 cubicle located at the Idaho National Engineering Laboratory (INEL). The HB-2 cubicle became radioactively contaminated during out-of-pile circulating water loop experiments conducted in the Materials Testing Reactor in the 1950s and 1960s. This paper describes work performed to accomplish the D and D objectives of reducing the high radiation fields caused by contamination inside the cubicle, preventing future contamination spread, and making about 1400 ft 2 of floor space available for reuse. Decommissioning of the HB-2 cubicle consisted of total dismantlement of the cubicle and its contents and was performed without disrupting ongoing laboratory work being conducted in areas surrounding the HB-2 cubicle. 3 refs., 7 figs., 4 tabs

  7. Fetal Anemia and Hydrops Fetalis Associated with Homozygous Hb Constant Spring (HBA2: c.427T > C).

    Science.gov (United States)

    He, Yi; Zhao, Ying; Lou, Ji-Wu; Liu, Yan-Hui; Li, Dong-Zhi

    2016-01-01

    Hb Constant Spring (Hb CS, HBA2: c.427T > C) is a common nondeletional α-thalassemia (α-thal) that results from a nucleotide substitution at the termination codon of the α2-globin gene. Homozygosity for Hb CS (α(CS)α/α(CS)α) is relatively rare, and generally characterized with mild hemolytic anemia, jaundice, and splenomegaly. In this report we present a fetus with cardiomegaly, pericardial effusion, enlarged placenta and increased middle cerebral artery-peak systolic velocity (MCA-PSV) at 24 weeks' gestation. Fetal blood sampling revealed the severe anemia [hemoglobin (Hb) level being 4.8 g/dL] and Hb H (β4) disease-like hematological findings with Hb Bart's (γ4) level of 17.9%. DNA sequencing of the α-globin genes found that both partners were Hb CS carriers and the fetus was an Hb CS homozygote. Therefore, this was a rare case of homozygous Hb CS which demonstrated an unusual and serious anemia and hydrops fetalis in utero.

  8. HbA1c Identifies Subjects With Prediabetes and Subclinical Left Ventricular Diastolic Dysfunction.

    Science.gov (United States)

    Di Pino, Antonino; Mangiafico, Sarah; Urbano, Francesca; Scicali, Roberto; Scandura, Salvatore; D'Agate, Veronica; Piro, Salvatore; Tamburino, Corrado; Purrello, Francesco; Rabuazzo, Agata Maria

    2017-10-01

    Prediabetes is associated with subclinical cardiac changes associated with heart failure development. We investigated diastolic function and its association with markers of glycation and inflammation related to cardiovascular disease in patients with prediabetes. We focused on individuals with prediabetes identified only by glycated hemoglobin A1c [HbA1c; 5.7% to 6.4% and normal fasting glucose (NFG) and normal glucose tolerance (NGT) after an oral glucose tolerance test (OGTT)]. Cross-sectional study. Departments of Clinical and Experimental Medicine and Cardiology, University of Catania, Catania, Italy. HbA1c, OGTT, Doppler echocardiography, soluble receptor for advanced glycation end products (sRAGEs), and endogenous secretory RAGE (esRAGE) were evaluated. We recruited 167 subjects with NFG/NGT who were stratified according to HbA1c level: controls (HbA1c prediabetes (HbA1c 5.7% to 6.4%). Patients with HbA1c prediabetes (n = 106) showed a lower peak mitral inflow in early diastole (E wave) to late diastolic atrial filling velocity (A wave) ratio (E/A ratio) than controls (n = 61) (1.10 ± 0.24 vs 1.18 ± 0.23; P prediabetes exhibited subclinical cardiac alterations associated with sRAGE, esRAGE, and HbA1c. These subjects would not have been classified as having prediabetes on the basis of fasting glycemia or post-OGTT values. Copyright © 2017 Endocrine Society

  9. Decontamination and decommissioning of the MTR-603 HB-2 cubicle. Final report

    International Nuclear Information System (INIS)

    Smith, D.L.

    1985-12-01

    This report describes the decontamination and decommissioning (D and D) of the MTR-603 HB-2 cubicle located at the Idaho National Engineering Laboratory (INEL). The HB-2 cubicle became radioactively contaminated during out-of-pile circulating water loop experiments conducted in the Materials Testing Reactor in the 1950s and 1960s. This report describes work performed to accomplish the D and D objectives of reducing the high radiation fields caused by contamination inside the cubicle, preventing future contamination spread, and making about 1400 ft 2 of floor space available for reuse. D and D of the HB-2 cubicle consisted of total dismantlement of the cubicle and its contents

  10. HbA1c and the Prediction of Type 2 Diabetes in Children and Adults.

    Science.gov (United States)

    Vijayakumar, Pavithra; Nelson, Robert G; Hanson, Robert L; Knowler, William C; Sinha, Madhumita

    2017-01-01

    Long-term data validating glycated hemoglobin (HbA 1c ) in assessing the risk of type 2 diabetes in children are limited. HbA 1c , fasting plasma glucose (FPG), and 2-h postload plasma glucose (2hPG) concentrations were measured in a longitudinal study of American Indians to determine their utility in predicting incident diabetes, all of which is thought to be type 2 in this population. Incident diabetes (FPG ≥126 mg/dL [7.0 mmol/L], 2hPG ≥200 mg/dL [11.1 mmol/L], HbA 1c ≥6.5% [8 mmol/mol], or clinical diagnosis) was determined in 2,095 children without diabetes ages 10-19 years monitored through age 39, and in 2,005 adults ages 20-39 monitored through age 59. Areas under the receiver operating characteristic (ROC) curve for HbA 1c , FPG, and 2hPG in predicting diabetes within 10 years were compared. During long-term follow-up of children and adolescents who did not initially have diabetes, the incidence rate of subsequent diabetes was fourfold (in boys) as high and more than sevenfold (in girls) as high in those with HbA 1c ≥5.7% as in those with HbA 1c ≤5.3%-greater rate ratios than experienced by adults in the same HbA 1c categories. Analyses of ROCs revealed no significant differences between HbA 1c , FPG, and 2hPG in sensitivity and specificity for identifying children and adolescents who later developed diabetes. HbA 1c is a useful predictor of diabetes risk in children and can be used to identify prediabetes in children with other type 2 diabetes risk factors with the same predictive value as FPG and 2hPG. © 2017 by the American Diabetes Association.

  11. Impact of Disease Management Programs on HbA1c Values in Type 2 Diabetes Patients in Germany.

    Science.gov (United States)

    Kostev, Karel; Rockel, Timo; Jacob, Louis

    2017-01-01

    The aim was to analyze the impact of disease management programs on HbA1c values in type 2 diabetes mellitus (T2DM) patients in Germany. This study included 9017 patients followed in disease management programs (DMPs) who started an antihyperglycemic treatment upon inclusion in a DMP. Standard care (SC) patients were included after individual matching (1:1) to DMP cases based on age, gender, physician (diabetologist versus nondiabetologist care), HbA1c values at baseline, and index year. The main outcome was the share of patients with HbA1c HbA1c level as a dependent variable and the potential predictor (DMP versus SC). The mean age was 64.3 years and 54.7% of the patients were men. The mean HbA1c level at baseline was equal to 8.7%. In diabetologist practices, 64.7% of DMP patients and 55.1% of SC patients had HbA1c levels HbA1c levels HbA1c levels HbA1c levels HbA1c levels lower than 7.5% or 6.5% after 6 months of therapy in both diabetologist and general care practices. The present study indicates that the enrollment of T2DM patients in DMPs has a positive impact on HbA1c values in Germany.

  12. TGF{beta} induces proHB-EGF shedding and EGFR transactivation through ADAM activation in gastric cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Ebi, Masahide [Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya (Japan); Kataoka, Hiromi, E-mail: hkataoka@med.nagoya-cu.ac.jp [Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya (Japan); Shimura, Takaya; Kubota, Eiji; Hirata, Yoshikazu; Mizushima, Takashi; Mizoshita, Tsutomu; Tanaka, Mamoru; Mabuchi, Motoshi; Tsukamoto, Hironobu; Tanida, Satoshi; Kamiya, Takeshi [Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya (Japan); Higashiyama, Shigeki [Department of Biochemistry and Molecular Genetics, Ehime University Graduate School of Medicine, Ehime (Japan); Joh, Takashi [Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya (Japan)

    2010-11-19

    Research highlights: {yields} TGF{beta} induces EGFR transactivation through proHB-EGF shedding by activated ADAM members in gastric cancer cells. {yields} TGF{beta} induces nuclear translocation of HB-EGF-CTF cleaved by ADAM members. {yields} TGF{beta} enhances cell growth by EGFR transactivation and HB-EGF-CTF nuclear translocation and ADAM inhibitors block these effects. {yields} Silencing of ADAM17 also blocks EGFR transactivation, HB-EGF-CTF nuclear translocation and cancer cell growth by TGF{beta}. {yields} ADAM17 may play a crucial role in this TGF{beta}-HB-EGF signal transduction. -- Abstract: Background and aims: Transforming growth factor-beta (TGF{beta}) is known to potently inhibit cell growth. Loss of responsiveness to TGF{beta} inhibition on cell growth is a hallmark of many types of cancer, yet its mechanism is not fully understood. Membrane-anchored heparin-binding EGF-like growth factor (proHB-EGF) ectodomain is cleaved by a disintegrin and metalloproteinase (ADAM) members and is implicated in epidermal growth factor receptor (EGFR) transactivation. Recently, nuclear translocation of the C-terminal fragment (CTF) of pro-HB-EGF was found to induce cell growth. We investigated the association between TGF{beta} and HB-EGF signal transduction via ADAM activation. Materials and methods: The CCK-8 assay in two gastric cancer cell lines was used to determine the effect for cell growth by TGF{beta}. The effect of two ADAM inhibitors was also evaluated. Induction of EGFR phosphorylation by TGF{beta} was analyzed and the effect of the ADAM inhibitors was also examined. Nuclear translocation of HB-EGF-CTF by shedding through ADAM activated by TGF{beta} was also analyzed. EGFR transactivation, HB-EGF-CTF nuclear translocation, and cell growth were examined under the condition of ADAM17 knockdown. Result: TGF{beta}-induced EGFR phosphorylation of which ADAM inhibitors were able to inhibit. TGF{beta} induced shedding of proHB-EGF allowing HB-EGF-CTF to

  13. Significance of HbA1c and its measurement in the diagnosis of diabetes mellitus: US experience.

    Science.gov (United States)

    Juarez, Deborah Taira; Demaris, Kendra M; Goo, Roy; Mnatzaganian, Christina Louise; Wong Smith, Helen

    2014-01-01

    The 2014 American Diabetes Association guidelines denote four means of diagnosing diabetes. The first of these is a glycosylated hemoglobin (HbA1c) >6.5%. This literature review summarizes studies (n=47) in the USA examining the significance, strengths, and limitations of using HbA1c as a diagnostic tool for diabetes, relative to other available means. Due to the relatively recent adoption of HbA1c as a diabetes mellitus diagnostic tool, a hybrid systematic, truncated review of the literature was implemented. Based on these studies, we conclude that HbA1c screening for diabetes has been found to be convenient and effective in diagnosing diabetes. HbA1c screening is particularly helpful in community-based and acute care settings where tests requiring fasting are not practical. Using HbA1c to diagnose diabetes also has some limitations. For instance, HbA1c testing may underestimate the prevalence of diabetes, particularly among whites. Because this bias differs by racial group, prevalence and resulting estimates of health disparities based on HbA1c screening differ from those based on other methods of diagnosis. In addition, existing evidence suggests that HbA1c screening may not be valid in certain subgroups, such as children, women with gestational diabetes, patients with human immunodeficiency virus, and those with prediabetes. Further guidelines are needed to clarify the appropriate use of HbA1c screening in these populations.

  14. Influence of Erythropoiesis-Stimulating Agents on HbA1c and Fructosamine in Patients with Haemodialysis.

    Science.gov (United States)

    Rasche, Franz Maximilian; Ebert, Thomas; Beckmann, Julia; Busch, Volker; Barinka, Filip; Rasche, Wilma Gertrud; Lindner, Tom H; Schneider, Jochen G; Schiekofer, Stephan

    2017-06-01

    HbA1c is the most accepted laboratory parameter for the long term observation of glucose control. There is still much of a debate about the use of HbA1c as a metabolic indicator in diabetic patients (DM) on haemodialysis (HD) and erythropoiesis-stimulating agent (ESA) therapy because of the altered erythrocyte turn over in patients with chronic kidney disease and haemodialysis (CKD5D). In 102 CKD5 patients with and without diabetes mellitus, we examined the dose dependent variability in HbA1c and fructosamine levels under haemodialysis and treated with epoetin α (n=48) and a new generation agent with continuous stimulation of methoxy polyethylene glycol epoetin beta (C.E.R.A.; n=54). HbA1c levels were affected by therapy with ESA treatments. ESA dose was inversely correlated with HbA1c and an escalation of 10.000 IU per week induced an estimated decrease of HbA1c of 0.6 percent. In addition, the increase of reticulocyte number as a marker for erythropoiesis was significantly inversely correlated with the increase of ΔHbA1c. ESA treatments had no such effect on the alternative metabolic parameter fructosamine. When compared, both therapeutic agents had comparable success in attaining haemoglobin (Hb) target values. C.E.R.A. showed better correlation and was more effective over a longer dose interval. Our results show that HbA1c levels in patients should be carefully interpreted based on interfering factors. Nevertheless, HbA1c is currently the most consistent parameter for use ascertaining metabolic status of patients suffering from diabetes mellitus. © Georg Thieme Verlag KG Stuttgart · New York.

  15. Change in Sedentary Time, Physical Activity, Bodyweight, and HbA1c in High-Risk Adults.

    Science.gov (United States)

    McCarthy, Matthew; Edwardson, Charlotte L; Davies, Melanie J; Henson, Joseph; Gray, Laura; Khunti, Kamlesh; Yates, Thomas

    2017-06-01

    In recent years, there has been a migration toward the use of glycated hemoglobin (HbA1c) in determining glycemic control. This study aimed to quantify the associations between changes in body weight, sedentary time, and moderate to vigorous physical activity (MVPA) time with HbA1c levels for a 3-yr period among adults at high risk of type 2 diabetes. This study reports baseline and 3-yr follow-up data from the Walking Away from Type 2 Diabetes study. ActiGraph GT3X accelerometers captured sedentary time and MVPA. Linear regression examined the independent associations of changes in sedentary time, MVPA, and body weight with HbA1c between baseline and 3-yr follow-up. The sample composed of 489 participants (mean age = 64.2 ± 7.3 yr, body mass index = 31.7 ± 5.1, 63.4% male) with valid baseline and follow-up accelerometer, body weight, and HbA1c data. After adjustment for known confounders, an increase in MVPA time (per 30 min·d) was associated with a decrease in HbA1c percentage (β = -0.11 [-0.18 to -0.05], P = 0.001), and an increase in body weight (per 6 kg) was associated with an increase in HbA1c percentage (β = 0.08 [0.04-0.12], P HbA1c ≥ 6.0%) strengthened these associations (P HbA1c after adjustment for change in MVPA time. Increases in MVPA and body weight were associated with a reduction and increase in HbA1c, respectively, particularly in those with dysglycemia. Quantifying the effect that health behavior changes have on HbA1c can be used to inform prevention programs.

  16. Serum testosterone levels of HbSS (sickle cell disease male subjects in Lagos, Nigeria

    Directory of Open Access Journals (Sweden)

    Adediran Adewumi

    2011-08-01

    Full Text Available Abstract Background Infertility is a major problem in sickle cell disease patients, especially in males. In addition to low serum testosterone, other abnormalities involving the accessory sex organs, such as the seminal vesicles and the prostate gland, as well as marked decrease in ejaculate volume may be observed in male HbSS patients. Hence, the need to study the role of sex hormones as a cause of infertility in male HbSS patients. Methods An unmatched case-control study was performed using seventy-five consenting subjects from Lagos University Teaching Hospital. These included 47 patients with haemoglobin phenotype SS from the Sickle cell clinic and 28 volunteered medical students and members of staff with haemoglobin phenotype AA. Demographic data were obtained using a self-administered questionnaire. A total of 5 mls of blood was collected from each subject between 9.00 am & 11.am, and assayed for serum testosterone concentration. Results The concentrations of serum testosterone in HbSS patients ranged from 0.2 to 4.3 ng/ml with a mean of 1.28 ± 0.72 ng/ml whilst the values in HbAA controls ranged from 1.2 to 6.9 ng/ml with a mean of 2.63 ± 1.04 ng/ml. Seven (25.0% of the 28 controls had serum testosterone concentration lower than the quoted reference (normal range whereas 44 (93.6% of the 47 HbSS subjects had serum testosterone concentration lower than the reference range. Conclusion Overall, subjects with HbSS have significantly lower mean serum testosterone than HbAA controls.

  17. HB 1347 and Its Relationship to Foodservice Outsourcing in Illinois Public Schools

    Science.gov (United States)

    Brashear, Gary L.

    2012-01-01

    This study examined foodservice outsourcing in the State of Illinois. School administrators currently outsourcing foodservice were surveyed about their perceptions of HB1347 and its components. This study looked at HB1347 in Illinois, and its effects on outsourcing in school districts. Data for this study was collected from a survey sent to 100%…

  18. High maternal HbA1c is associated with overweight in neonates

    DEFF Research Database (Denmark)

    Mikkelsen, Maria R.; Nielsen, Sigrid Bruun; Stage, E

    2011-01-01

    The aims of this study were to determine the prevalence of women with gestational diabetes mellitus (GDM) not obtaining HbA1c within the normal range (= 5.6%) before delivery and to examine whether elevated HbA1c values are associated with an increased risk of large for gestational age (LGA) infa...

  19. Convergent Evolution of Hemoglobin Function in High-Altitude Andean Waterfowl Involves Limited Parallelism at the Molecular Sequence Level.

    Directory of Open Access Journals (Sweden)

    Chandrasekhar Natarajan

    2015-12-01

    Full Text Available A fundamental question in evolutionary genetics concerns the extent to which adaptive phenotypic convergence is attributable to convergent or parallel changes at the molecular sequence level. Here we report a comparative analysis of hemoglobin (Hb function in eight phylogenetically replicated pairs of high- and low-altitude waterfowl taxa to test for convergence in the oxygenation properties of Hb, and to assess the extent to which convergence in biochemical phenotype is attributable to repeated amino acid replacements. Functional experiments on native Hb variants and protein engineering experiments based on site-directed mutagenesis revealed the phenotypic effects of specific amino acid replacements that were responsible for convergent increases in Hb-O2 affinity in multiple high-altitude taxa. In six of the eight taxon pairs, high-altitude taxa evolved derived increases in Hb-O2 affinity that were caused by a combination of unique replacements, parallel replacements (involving identical-by-state variants with independent mutational origins in different lineages, and collateral replacements (involving shared, identical-by-descent variants derived via introgressive hybridization. In genome scans of nucleotide differentiation involving high- and low-altitude populations of three separate species, function-altering amino acid polymorphisms in the globin genes emerged as highly significant outliers, providing independent evidence for adaptive divergence in Hb function. The experimental results demonstrate that convergent changes in protein function can occur through multiple historical paths, and can involve multiple possible mutations. Most cases of convergence in Hb function did not involve parallel substitutions and most parallel substitutions did not affect Hb-O2 affinity, indicating that the repeatability of phenotypic evolution does not require parallelism at the molecular level.

  20. Identificação molecular da uva 'Goethe' de Urussanga - SC por marcadores microssatélites Molecular identification of the grapevine 'Goethe' from Urussanga (SC with microsatellite markers

    Directory of Open Access Journals (Sweden)

    Mariane Ruzza Schuck

    2010-09-01

    Full Text Available A variedade Goethe é símbolo da vitivinicultura da região de Urussanga, sul do Estado de Santa Catarina, a qual, atualmente, busca a Indicação Geográfica da Uva e do Vinho Goethe. Para isto, um dos requisitos necessários é a identificação precisa do material genético. Os marcadores microssatélites constituem a ferramenta molecular mais utilizada para a identificação varietal de videira em todo o mundo e têm a capacidade de produzir um perfil genético único para cada material vitícola. O objetivo deste trabalho foi caracterizar duas seleções de uva 'Goethe', presentes no município de Urussanga, por meio de marcadores moleculares microssatélites, visando a atender aos requisitos de denominação de origem e indicação de procedência controlada. A extração do DNA genômico foi realizada a partir de folhas jovens e ramos de nove acessos de cada seleção de 'Goethe Classica' e 'Goethe Primo' provenientes de uma coleção pública e de oito coleções privadas da região de Urussanga. Dez loci microssatélites VVS2, VVMD5, VVMD7, VVMD27, VrZAG62, VrZAG79, VVMD25, VVMD28, VVMD31 e VVMD32 foram genotipados através de eletroforese capilar. As análises realizadas mostraram que as duas variantes da uva 'Goethe' apresentaram um perfil molecular idêntico e único, isto é, representam a mesma variedade e sem nenhuma correspondência com variedades descritas anteriormente na literatura e nos bancos de dados consultados. As diferenças fenotípicas observadas provavelmente são devidas a mutações somáticas em regiões funcionais do genoma, fenômeno que dá origem aos clones em videira.'Goethe' grape is a symbol of the viticulture of Urussanga region, South of Santa Catarina State, which is currently claiming the geographical indication of the grape and wine Goethe. Microsatellite markers are the biotechnological tool most used for molecular identification of grapevine varieties worldwide. These markers have the potential of

  1. PEGYLATION OF αα-Hb USING SUCCINIMIDYL PROPIONIC ACID PEG 5K

    Science.gov (United States)

    Meng, Fantao; Tsai, Amy G.; Intaglietta, Marcos; Acharya, Seetharama A.

    2014-01-01

    PEGylation of intramolecularly crosslinked Hb has been studied here to overcome the limitation of dissociation of Hb tetramers. New hexa and deca PEGylated low oxygen affi nity PEG-αα-Hbs have been generated. Infl uence of PEG conjugation chemistry and the PEG shell structure on the functional properties as well as PEGylation induced plasma expander like properties of the protein has been delineated. The results have established that in the design of PEG-Hbs as oxygen therapeutics, the infl uence of conjugation chemistry and the PEG shell structure on the oxygen affi nity of Hb needs to be optimized independently besides optimizing the PEG shell structure for inducing resuscitation fluid like properties. PMID:24597567

  2. Influence of Molecular Structure on O2-Binding Properties and Blood Circulation of Hemoglobin‒Albumin Clusters.

    Directory of Open Access Journals (Sweden)

    Kana Yamada

    Full Text Available A hemoglobin wrapped covalently by three human serum albumins, a Hb-HSA3 cluster, is an artificial O2-carrier with the potential to function as a red blood cell substitute. This paper describes the synthesis and O2-binding properties of new hemoglobin‒albumin clusters (i bearing four HSA units at the periphery (Hb-HSA4, large-size variant and (ii containing an intramolecularly crosslinked Hb in the center (XLHb-HSA3, high O2-affinity variant. Dynamic light scattering measurements revealed that the Hb-HSA4 diameter is greater than that of either Hb-HSA3 or XLHb-HSA3. The XLHb-HSA3 showed moderately high O2-affinity compared to the others because of the chemical linkage between the Cys-93(β residues in Hb. Furthermore, the blood circulation behavior of 125I-labeled clusters was investigated by assay of blood retention and tissue distribution after intravenous administration into anesthetized rats. The XLHb-HSA3 was metabolized faster than Hb-HSA3 and Hb-HSA4. Results suggest that the molecular structure of the protein cluster is a factor that can influence in vivo circulation behavior.

  3. HB-GAM (pleiotrophin) reverses inhibition of neural regeneration by the CNS extracellular matrix

    Science.gov (United States)

    Paveliev, Mikhail; Fenrich, Keith K.; Kislin, Mikhail; Kuja-Panula, Juha; Kulesskiy, Evgeny; Varjosalo, Markku; Kajander, Tommi; Mugantseva, Ekaterina; Ahonen-Bishopp, Anni; Khiroug, Leonard; Kulesskaya, Natalia; Rougon, Geneviève; Rauvala, Heikki

    2016-01-01

    Chondroitin sulfate (CS) glycosaminoglycans inhibit regeneration in the adult central nervous system (CNS). We report here that HB-GAM (heparin-binding growth-associated molecule; also known as pleiotrophin), a CS-binding protein expressed at high levels in the developing CNS, reverses the role of the CS chains in neurite growth of CNS neurons in vitro from inhibition to activation. The CS-bound HB-GAM promotes neurite growth through binding to the cell surface proteoglycan glypican-2; furthermore, HB-GAM abrogates the CS ligand binding to the inhibitory receptor PTPσ (protein tyrosine phosphatase sigma). Our in vivo studies using two-photon imaging of CNS injuries support the in vitro studies and show that HB-GAM increases dendrite regeneration in the adult cerebral cortex and axonal regeneration in the adult spinal cord. Our findings may enable the development of novel therapies for CNS injuries. PMID:27671118

  4. Anemia ferropriva em escolares da primeira série do ensino fundamental da rede pública de educação de uma região de Brasília, DF Iron deficiency anemia in first grade students from public schools in a region of Brasília, DF

    Directory of Open Access Journals (Sweden)

    Gracy Santos Heijblom

    2007-06-01

    Full Text Available A anemia ferropriva é a deficiência de micronutriente mais prevalente no mundo. É particularmente deletéria em escolares, pois crianças anêmicas são sonolentas e prestam menos atenção. Como conseqüência, pode levar ao alto absenteísmo e baixo rendimento escolar. Realizou-se um estudo transversal com amostra probabilística de 424 alunos de 6 a 11 anos, da 1ª série do ensino fundamental de escolas públicas da Regional Norte de Saúde de Brasília. Os objetivos foram avaliar a prevalência de anemia e comparar o resultado obtido em 2004 com aquele de estudo similar realizado na mesma área em 1998. A hemoglobina (Hb foi determinada em amostra de sangue digital, usando Hemocue®. Dois pontos de corte foram adotados para classificar anemia, ambos estabelecidos pela Organização Mundial da Saúde: HbIron deficiency anemia (IDA is the most prevalent micronutrient deficiency in the world. In school age children, IDA is particularly deleterious: anemic children are sleepy and pay less attention. As a consequence, anemia can lead to high absenteeism and lower school performance. A cross-sectional survey was conducted in a representative sample of 424 randomly selected first graders (ages 6 to 11 years from public schools located in the Northern Public Health Region of Brasília. The study objectives were to: (a determine the prevalence of anemia; (b compare the results obtained in 2004 to those of a similar survey conducted in the same area in 1998. Hemoglobin (Hb was determined in finger-prick blood samples using Hemocue®. Two cut-off points were used to classify anemia, both established by the WHO: Hb<11.5g/dL and Hb<12.0g/dL. The height/age, weight/age and weight/height indicators below -2.0 standard deviations from the NCHS reference were used to indicate growth retardation. Prevalence of anemia was 12.5% and 11.9% (Hb<11.5g/dL and 26.9% and 21.5% (Hb<12.0g/dL in 2004 and 1998 respectively. The prevalence of anemia increased between

  5. HbA1c Test as a Tool in the Diagnosis of Gestational Diabetes Mellitus.

    Directory of Open Access Journals (Sweden)

    Paula Breitenbach Renz

    Full Text Available Gestational diabetes mellitus (GDM is a prevalent and potentially serious condition which may put both mothers and neonates at risk. The current recommendation for diagnosis is the oral glucose tolerance test (OGTT. This study aimed to determine the usefulness of HbA1c test as a diagnostic tool for GDM as compared to the traditional criteria based on the OGTT.This was a diagnostic test accuracy study. We performed OGTT and HbA1c test in women attending prenatal visits at a tertiary hospital. GDM was defined according to WHO1999 or ADA/WHO 2013 criteria. ROC curve was used to evaluate the diagnostic performance of HbA1c. Sensitivity, specificity and likelihood ratios for different HbA1c cut-off points were calculated.Of the 262 women in the third trimester of gestation enrolled in the study, 86 (33% were diagnosed with GDM. Only five of these women presented HbA1c ≥48 mmol/mol (6.5%. This cut-off point presented 100% specificity but very low sensitivity (7%. Based on ROC curve, and considering OGTT as the reference criterion, HbA1c ≥40 mmol/mol (5.8% showed adequate specificity in diagnosing GDM (94.9% but low sensitivity (26.4%. Unlike, HbA1c values of 31 mmol/mol (5.0% presented adequate sensitivity (89.7% but low specificity (32.6% to detect GDM. For women with HbA1c ≥40 mmol/mol (5.8%, the positive and negative likelihood ratios were 5.14 (95%CI 2.49-10.63 and 0.78 (0.68-0.88, respectively. The post-test probability of GDM was about 40%, representing a 4.0-fold increase in the mean pre-test probability. This cut-off point could eliminate the need for the unpleasant and laborious OGTT tests in almost one third of cases, as 38% of patients with GDM may be diagnosable by HbA1c test alone.Our results show that combined HbA1c and OGTT measurements may be useful in diagnosing GDM.

  6. Prevalence of Diabetes and Prediabetes according to Fasting Plasma Glucose and HbA1c

    Science.gov (United States)

    Jeon, Ja Young; Ko, Seung-Hyun; Kwon, Hyuk-Sang; Kim, Nan Hee; Kim, Jae Hyeon; Kim, Chul Sik; Song, Kee-Ho; Won, Jong Chul; Lim, Soo; Choi, Sung Hee; Jang, Myoung-jin; Kim, Yuna; Oh, Kyungwon

    2013-01-01

    Background Due to the inconvenience of performing oral glucose tolerance tests and day to day variability in glucose level, glycated hemoglobin (HbA1c) has been recommended by the American Diabetes Association as a method to diagnose diabetes. In addition, the Korean Diabetes Association has also recommended the use of HbA1c as a diagnostic test for diabetes. In this study, we evaluated the prevalence of diabetes according to fasting plasma glucose (FPG) level only or the combination of FPG and HbA1c tests. Methods Data from the 2011 Korea National Health and Nutrition Examination Survey (KNHANES) were analyzed. Among 5,811 subjects aged 30 years or older, 5,020 were selected after excluding the data of fasting time <8 hours, missing values from fasting glucose or HbA1c level, previous diagnosis of diabetes made by physicians, or current use of antidiabetic medications. Diabetes was defined as FPG ≥126 mg/dL, previous diagnosis of diabetes made by a medical doctor, current use of antidiabetic medications, and/or HbA1c ≥6.5%. Prediabetes was defined as FPG of 100 to 125 mg/dL and/or HbA1c of 5.7% to 6.4%. Results When we used FPG only, the prevalence of diabetes and prediabetes were 10.5% (men, 12.6%; women, 8.5%) and 19.3% (men, 23.8%; women, 14.9%), respectively. When HbA1c was included as a diagnostic test, the prevalence of diabetes and prediabetes increased to 12.4% (men, 14.5%; women, 10.4%) and 38.3% (men, 41%; women, 35.7%), respectively. Participants with HbA1c ≥6.5% and fasting glucose level <126 mg/dL were older and had lower estimated glomerular filtration rate. Conclusion We concluded that using fasting glucose level only may result in an underestimation of diabetes and prediabetes. HbA1c is an acceptable complementary diagnostic test for diabetes in Korean patients. However, national standardization is needed to order to use HbA1c as a diagnostic method of diabetes and prediabetes. PMID:24199164

  7. Prevalence of Diabetes and Prediabetes according to Fasting Plasma Glucose and HbA1c

    Directory of Open Access Journals (Sweden)

    Ja Young Jeon

    2013-10-01

    Full Text Available BackgroundDue to the inconvenience of performing oral glucose tolerance tests and day to day variability in glucose level, glycated hemoglobin (HbA1c has been recommended by the American Diabetes Association as a method to diagnose diabetes. In addition, the Korean Diabetes Association has also recommended the use of HbA1c as a diagnostic test for diabetes. In this study, we evaluated the prevalence of diabetes according to fasting plasma glucose (FPG level only or the combination of FPG and HbA1c tests.MethodsData from the 2011 Korea National Health and Nutrition Examination Survey (KNHANES were analyzed. Among 5,811 subjects aged 30 years or older, 5,020 were selected after excluding the data of fasting time <8 hours, missing values from fasting glucose or HbA1c level, previous diagnosis of diabetes made by physicians, or current use of antidiabetic medications. Diabetes was defined as FPG ≥126 mg/dL, previous diagnosis of diabetes made by a medical doctor, current use of antidiabetic medications, and/or HbA1c ≥6.5%. Prediabetes was defined as FPG of 100 to 125 mg/dL and/or HbA1c of 5.7% to 6.4%.ResultsWhen we used FPG only, the prevalence of diabetes and prediabetes were 10.5% (men, 12.6%; women, 8.5% and 19.3% (men, 23.8%; women, 14.9%, respectively. When HbA1c was included as a diagnostic test, the prevalence of diabetes and prediabetes increased to 12.4% (men, 14.5%; women, 10.4% and 38.3% (men, 41%; women, 35.7%, respectively. Participants with HbA1c ≥6.5% and fasting glucose level <126 mg/dL were older and had lower estimated glomerular filtration rate.ConclusionWe concluded that using fasting glucose level only may result in an underestimation of diabetes and prediabetes. HbA1c is an acceptable complementary diagnostic test for diabetes in Korean patients. However, national standardization is needed to order to use HbA1c as a diagnostic method of diabetes and prediabetes.

  8. Molecular diagnosis of Huntington disease in Brazilian patients Diagnóstico molecular da doença de Huntington em pacientes brasileiros

    Directory of Open Access Journals (Sweden)

    TEREZA C. LIMA E SILVA

    2000-03-01

    ós o início da doença. A HD está associada a uma expansão trinucleotídica CAG presente na porção 5' do gene IT15. Nós investigamos a repetição CAG no gene IT15 em 44 indivíduos brasileiros (42 pacientes e 2 membros não afetados de uma família pertencentes a 34 famílias não relacionadas com diagnóstico provável de HD. Um alelo CAG expandido foi encontrado em 32 indivíduos (76% pertencentes a 25 famílias não relacionadas. Nos pacientes com a mutação HD, os alelos expandidos variaram de 43 a 73 unidades de repetição CAG e os alelos normais apresentaram variação de 18 a 26 CAGs. Correlação negativa significativa foi encontrada entre a idade de início dos sintomas e o tamanho da expansão trinucleotídica CAG (r=0,6; p=0,0001; no entanto, o tamanho da repetição CAG expandida foi capaz de explicar somente 40% da variação encontrada na idade de início da doença (r2=0,4. Além disso, nós genotipamos um total de 25 indivíduos pertencentes a um grupo controle da população brasileira (total de 50 alelos, sendo que o alelo normal apresentou variação de 16 a 33 unidades de repetição CAG. A porcentagem de heterozigozidade do alelo normal na população brasileira controle foi 88%. Em conclusão, nossos resultados mostraram que nem todos os pacientes com fenótipo ``HD'' possuíam a expansão CAG no gene IT15. O diagnóstico molecular foi possível em todos os indivíduos analisados nesse estudo, não sendo encontrada em nossa amostra nenhum alelo de tamanho intermediário. Portanto, nós recomendamos que a confirmação molecular do diagnóstico na HD deva ser realizada em todos os casos suspeitos, a fim de proporcionar subsídios para um aconselhamento genético adequado.

  9. Molecular Diagnostics of ?-Thalassemia

    OpenAIRE

    Atanasovska, B; Bozhinovski, G; Chakalova, L; Kocheva, S; Karanfilski, O; Plaseska-Karanfiska, D

    2012-01-01

    A high-quality hemoglobinopathy diagnosis is based on the results of a number of tests including assays for molecular identification of causative mutations. We describe the current diagnostic strategy for the identification of ?-thalassemias and hemoglobin (Hb) variants at the International Reference Laboratory for Haemoglobinopathies, Research Centre for Genetic Engineering and Biotechnology (RCGEB) ?Georgi D. Efremov,? Skopje, Republic of Macedonia. Our overall approach and most of the meth...

  10. [Assays of HbA1c and Amadori products in human biology].

    Science.gov (United States)

    Gillery, P

    2014-09-01

    Different Amadori products, formed during the early steps of the non-enzymatic glycation of proteins, may be assayed in current practice in human biology. The most important marker is HbA1c, resulting from the binding of glucose to the N-terminal extremity of HbA beta chains. HbA1c may be evaluated by various techniques (ion exchange or affinity high performance liquid chromatography, capillary electrophoresis, immunoassay, enzymatic technique) and is considered the best marker of diabetic patient survey. Due to its irreversible and cumulative formation, it provides a retrospective information on the glycemic balance over the four to eight weeks preceding blood collection. It benefits from an international standardization, based on a reference method using liquid chromatography coupled to capillary electrophoresis or mass spectrometry, maintained by an international network of reference laboratories. When HbA1c assay cannot be used (anemia, hemolysis, hemoglobinopathy) or when a shorter period of glycemic equilibrium must be evaluated (child and adolescent, pregnancy, therapeutic changes), other Amadori products may be assayed, like plasma fructosamine (all plasma glycated proteins) or glycated albumin. Nevertheless, these assays are less used in practice, because their semiological value has been less evidenced. Besides, fructosamine assay lacks specificity, and glycated albumin assay has been described recently. An expanding use of HbA1c assay is expected, especially for the diagnosis of diabetes mellitus and the evaluation of other risks, especially cardiovascular ones. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  11. Benchmarking by HbA1c in a national diabetes quality register--does measurement bias matter?

    Science.gov (United States)

    Carlsen, Siri; Thue, Geir; Cooper, John Graham; Røraas, Thomas; Gøransson, Lasse Gunnar; Løvaas, Karianne; Sandberg, Sverre

    2015-08-01

    Bias in HbA1c measurement could give a wrong impression of the standard of care when benchmarking diabetes care. The aim of this study was to evaluate how measurement bias in HbA1c results may influence the benchmarking process performed by a national diabetes register. Using data from 2012 from the Norwegian Diabetes Register for Adults, we included HbA1c results from 3584 patients with type 1 diabetes attending 13 hospital clinics, and 1366 patients with type 2 diabetes attending 18 GP offices. Correction factors for HbA1c were obtained by comparing the results of the hospital laboratories'/GP offices' external quality assurance scheme with the target value from a reference method. Compared with the uncorrected yearly median HbA1c values for hospital clinics and GP offices, EQA corrected HbA1c values were within ±0.2% (2 mmol/mol) for all but one hospital clinic whose value was reduced by 0.4% (4 mmol/mol). Three hospital clinics reduced the proportion of patients with poor glycemic control, one by 9% and two by 4%. For most participants in our study, correcting for measurement bias had little effect on the yearly median HbA1c value or the percentage of patients achieving glycemic goals. However, at three hospital clinics correcting for measurement bias had an important effect on HbA1c benchmarking results especially with regard to percentages of patients achieving glycemic targets. The analytical quality of HbA1c should be taken into account when comparing benchmarking results.

  12. Estudo do método da extração da camada leucoplaquetária na produção de hemocomponentes: avaliação laboratorial A study of the Buffy-coat extraction method for blood component processing: laboratorial analysis

    Directory of Open Access Journals (Sweden)

    Mario I. Serinolli

    2004-01-01

    Full Text Available Dentre os métodos para a obtenção de hemocomponentes destaca-se o método do plasma rico em plaquetas (PRP e o método da extração da camada leucoplaquetária (ECLP. Este estudo tem por objetivo comparar os métodos do PRP e da ECLP na produção de hemocomponentes. Foram processadas 88 bolsas de sangue total (ST pelo método do PRP, 130 bolsas triplas pelo método da ECLP (ECLPT e 215 bolsas coletadas em bolsas quádruplas pelo método da ECLP (ECLPQ com o uso de extrator automático. Encontramos diferença estatisticamente significante na quantidade de Hb total /unidade entre ECLPT e ECLPQ (p=0,005 e entre ECLPT e PRP (p=0,007 no ST. Houve diferença estatisticamente entre ECLPT e ECLPQ (pThe most commonly used methods for blood component processing are the "plasma rich in platelets method" (PRP, and the Buffy-coat extraction method (BC.The purpose of this study was to compare these two methods in the processing of blood components. Eighty-eight whole blood units (WB were processed by the PRP method, 130 blood units were processed by the BC triple blood bag method (BCT and 215 blood units were collected in quadruple blood bags by the BC method (BCQ using an automatic extractor. A statistically significant difference was observed in the number in the total Hb per unit of WB between the BCT and BCQ methods (p=0.005 and between the BCT and PRP methods (p=0.007. There were also statistically significant differences between the BCT and BCQ methods (p<0.001 and between BCQ and PRP methods (p<0.001 in relation to leukocytes/mL. In the RBC concentrates, we found statistically significant differences between the PRP method and both the BCT and BCQ methods in respect to hematocrit levels, Hb recovery, total Hb, leukocytes, leukocyte depletion, platelets and platelet depletion (p<0.001 in all cases. We also found statistically significant differences between the PRP, BCT and BCQ methods for the volume, platelet recovery, and leukocyte depletion (p<0

  13. A study assessing the association of glycated hemoglobin A1C (HbA1C) associated variants with HbA1C, chronic kidney disease and diabetic retinopathy in populations of Asian ancestry.

    Science.gov (United States)

    Chen, Peng; Ong, Rick Twee-Hee; Tay, Wan-Ting; Sim, Xueling; Ali, Mohammad; Xu, Haiyan; Suo, Chen; Liu, Jianjun; Chia, Kee-Seng; Vithana, Eranga; Young, Terri L; Aung, Tin; Lim, Wei-Yen; Khor, Chiea-Chuen; Cheng, Ching-Yu; Wong, Tien-Yin; Teo, Yik-Ying; Tai, E-Shyong

    2013-01-01

    Glycated hemoglobin A1C (HbA1C) level is used as a diagnostic marker for diabetes mellitus and a predictor of diabetes associated complications. Genome-wide association studies have identified genetic variants associated with HbA1C level. Most of these studies have been conducted in populations of European ancestry. Here we report the findings from a meta-analysis of genome-wide association studies of HbA1C levels in 6,682 non-diabetic subjects of Chinese, Malay and South Asian ancestries. We also sought to examine the associations between HbA1C associated SNPs and microvascular complications associated with diabetes mellitus, namely chronic kidney disease and retinopathy. A cluster of 6 SNPs on chromosome 17 showed an association with HbA1C which achieved genome-wide significance in the Malays but not in Chinese and Asian Indians. No other variants achieved genome-wide significance in the individual studies or in the meta-analysis. When we investigated the reproducibility of the findings that emerged from the European studies, six loci out of fifteen were found to be associated with HbA1C with effect sizes similar to those reported in the populations of European ancestry and P-value ≤ 0.05. No convincing associations with chronic kidney disease and retinopathy were identified in this study.

  14. A study assessing the association of glycated hemoglobin A1C (HbA1C associated variants with HbA1C, chronic kidney disease and diabetic retinopathy in populations of Asian ancestry.

    Directory of Open Access Journals (Sweden)

    Peng Chen

    Full Text Available Glycated hemoglobin A1C (HbA1C level is used as a diagnostic marker for diabetes mellitus and a predictor of diabetes associated complications. Genome-wide association studies have identified genetic variants associated with HbA1C level. Most of these studies have been conducted in populations of European ancestry. Here we report the findings from a meta-analysis of genome-wide association studies of HbA1C levels in 6,682 non-diabetic subjects of Chinese, Malay and South Asian ancestries. We also sought to examine the associations between HbA1C associated SNPs and microvascular complications associated with diabetes mellitus, namely chronic kidney disease and retinopathy. A cluster of 6 SNPs on chromosome 17 showed an association with HbA1C which achieved genome-wide significance in the Malays but not in Chinese and Asian Indians. No other variants achieved genome-wide significance in the individual studies or in the meta-analysis. When we investigated the reproducibility of the findings that emerged from the European studies, six loci out of fifteen were found to be associated with HbA1C with effect sizes similar to those reported in the populations of European ancestry and P-value ≤ 0.05. No convincing associations with chronic kidney disease and retinopathy were identified in this study.

  15. Evaluation of the HB&L System for the Microbiological Screening of Storage Medium for Organ-Cultured Corneas.

    Science.gov (United States)

    Camposampiero, D; Grandesso, S; Zanetti, E; Mazzucato, S; Solinas, M; Parekh, M; Frigo, A C; Gion, M; Ponzin, D

    2013-01-01

    Aims. To compare HB&L and BACTEC systems for detecting the microorganisms contaminating the corneal storage liquid preserved at 31°C. Methods. Human donor corneas were stored at 4°C followed by preservation at 31°C. Samples of the storage medium were inoculated in BACTEC Peds Plus/F (aerobic microorganisms), BACTEC Plus Anaerobic/F (anaerobic microorganisms), and HB&L bottles. The tests were performed (a) after six days of storage, (b) end of storage, and (c) after 24 hours of preservation in deturgescent liquid sequentially. 10,655 storage and deturgescent media samples were subjected to microbiological control using BACTEC (6-day incubation) and HB&L (24-hour incubation) systems simultaneously. BACTEC positive/negative refers to both/either aerobic and anaerobic positives/negatives, whereas HB&L can only detect the aerobic microbes, and therefore the positives/negatives depend on the presence/absence of aerobic microorganisms. Results. 147 (1.38%) samples were identified positive with at least one of the two methods. 127 samples (134 identified microorganisms) were positive with both HB&L and BACTEC. 14 HB&L+/BACTEC- and 6 BACTEC+/HB&L- were identified. Sensitivity (95.5%), specificity (99.8%), and positive (90.1%) and negative predictive values (99.9%) were high with HB&L considering a 3.5% annual contamination rate. Conclusion. HB&L is a rapid system for detecting microorganisms in corneal storage medium in addition to the existing methods.

  16. Efeitos da anemia materna na cardiotocografia computadorizada e perfil biofísico fetal Effects of maternal anemia on computerized cardiotocography and fetal biophysical profile

    Directory of Open Access Journals (Sweden)

    Roseli Mieko Yamamoto Nomura

    2009-12-01

    Full Text Available OBJETIVOS: avaliar a influência dos níveis de hemoglobina (Hb materna nos padrões da frequência cardíaca fetal (FCF e no perfil biofísico fetal (PBF em gestações a termo. MÉTODOS: gestantes portadoras de anemia (Hb11,0 g/dL. Foram excluídos casos com anomalias ou restrição do crescimento fetal. A avaliação da FCF foi realizada pela cardiotocografia computadorizada (Sistema8002-Sonicaid e análise do traçado com 30 minutos de exame. O PBF foi realizado em todas as pacientes. Foram utilizados os testes t de Student, teste do χ2 e teste exato de Fisher. O nível de significância utilizado foi de 0,05. RESULTADOS: A média da Hb materna no grupo com anemia (n=18 foi de 9,4 g/dL (DP=1,4 g/dL e no Grupo Controle 12,4 g/dL (DP=1,3 g/dL. Quanto aos parâmetros da cardiotocografia, não foi constatada diferença significativa nas médias entre os grupos com anemia e controle, respectivamente: FCF basal (131,3 bpm versus 133,7 bpm, p=0,5, acelerações da FCF > 10 bpm (7,9 versus. 8,2, p=0,866, acelerações da FCF > 15 bpm (5,2 versus 5,4, p=0,9, episódios de alta variação da FCF (17,1 versus 15,5 min, p=0,5, episódios de baixa variação da FCF (4,4 versus 3,6 min, p=0,6, e variação de curto prazo (10,5 versus 10,9 ms, p=0,5. Em ambos os grupos, todas as pacientes apresentaram PBF normal. CONCLUSÕES: este estudo sugere que a anemia materna leve ou moderada, sem outras comorbidades maternas ou fetais, não se associa a anormalidades nos parâmetros do perfil biofísico fetal e da FCF analisada pela cardiotocografia computadorizada.PURPOSES: to evaluate the influence of maternal hemoglobin (Hb levels in the patterns of fetal heart rate (FHR and in the fetal biophysical profile (FBP in term gestations. METHODS: pregnant women with anemia (Hb11,0 g/dL. Cases of anomalies or fetal growing restrictions were excluded. The FHR evaluation was performed by computerized cardiotocography (8002 System-Sonicaid, and by record analysis during

  17. Identification of Hb Constant Spring (HBA2: c.427T > C) by an Automated High Performance Liquid Chromatography Method.

    Science.gov (United States)

    Wisedpanichkij, Raewadee; Jindadamrongwech, Sumalee; Butthep, Punnee

    2015-01-01

    Laboratory investigation of hemoglobinopathies includes complete blood count (CBC), hemoglobin (Hb) typing by high performance liquid chromatography (HPLC) and DNA analysis. DNA analysis is the most reliable method but requires a manually laborious procedure and is time consuming. A more practical method of detecting abnormal Hbs is the HPLC technique, because it is more rapid and easier to interpret. Hb Constant Spring (Hb CS; HBA2: c.427T > C) is an abnormal variant that is labile and difficult to detect using conventional methods. To evaluate the efficiency of Hb CS determination by HPLC, blood samples from 578 subjects were analyzed using an automated cell analyzer for hematological parameters, automated HPLC for Hb identification, and polymerase chain reaction (PCR) for α-thalassemia (α-thal) and Hb CS confirmation. These included 169 normal, 119 heterozygous α-thal-2, 30 homozygous α-thal-2, 177 heterozygous α-thal-1, 59 heterozygous Hb CS, seven homozygous Hb CS and 17 compound heterozygous α-thal-2 and Hb CS subjects. The results showed that sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of Hb CS by HPLC were 93.78, 99.80, 98.73 and 99.00%, respectively. The mean of misdiagnosis value of the three groups of Hb CS subjects (total 83) was 6.02% (n = 5), with percentages for heterozygous Hb CS, homozygous Hb CS, and compound heterozygous α-thal-2 and Hb CS being 6.8, 0.0 and 5.9%, respectively. The HPLC method yielded good results, although it may also lead to misdiagnosis of Hb CS due to the relatively small amount and lability.

  18. Glycated haemoglobin (HbA1c), diabetes and trajectories of change in episodic memory performance.

    Science.gov (United States)

    Pappas, Colleen; Andel, Ross; Infurna, Frank J; Seetharaman, Shyam

    2017-02-01

    As the ageing population grows, it is important to identify strategies to moderate cognitive ageing. We examined glycated haemoglobin (HbA1c) and diabetes in relation to level and change in episodic memory in older adults with and without diabetes. Data from 4419 older adults with (n=950) and without (n=3469) diabetes participating in a nationally representative longitudinal panel study (the Health and Retirement Study) were examined. Average baseline age was 72.66 years and 58% were women. HbA1c was measured in 2006 and episodic memory was measured using immediate and delayed list recall over 4 biennial waves between 2006 and 2012. Growth curve models were used to assess trajectories of episodic memory change. In growth curve models adjusted for age, sex, education, race, depressive symptoms and waist circumference, higher HbA1c levels and having diabetes were associated with poorer baseline episodic memory (p=0.036 and HbA1c on episodic memory decline was smaller than the effect of age. The results were stronger for women than men and were not modified by age or race. When the main analyses were estimated for those with and without diabetes separately, HbA1c was significantly linked to change in episodic memory only among those with diabetes. Higher HbA1c and diabetes were both associated with declines in episodic memory, with this relationship further exacerbated by having diabetes and elevated HbA1c. HbA1c appeared more important for episodic memory performance among women than men. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  19. Trimester-specific reference intervals for haemoglobin A(1c) (HbA(1c)) in pregnancy.

    LENUS (Irish Health Repository)

    O'Connor, Catherine

    2011-11-26

    Abstract Background: Diabetes in pregnancy imposes additional risks to both mother and infant. These increased risks are considered to be primarily related to glycaemic control which is monitored by means of glycated haemoglobin (HbA(1c)). The correlation of HbA(1c) with clinical outcomes emphasises the need to measure HbA(1c) accurately, precisely and for correct interpretation, comparison to appropriately defined reference intervals. Since July 2010, the HbA(1c) assay in Irish laboratories is fully metrologically traceable to the IFCC standard. The objective was to establish trimester-specific reference intervals in pregnancy for IFCC standardised HbA(1c) in non-diabetic Caucasian women. Methods: The authors recruited 311 non-diabetic Caucasian pregnant (n=246) and non-pregnant women (n=65). A selective screening based on risk factors for gestational diabetes was employed. All subjects had a random plasma glucose <7.7 mmol\\/L and normal haemoglobin level. Pregnancy trimester was defined as trimester 1 (T1, n=40) up to 12 weeks +6 days, trimester 2 (T2, n=106) 13-27 weeks +6 days, trimester 3 (T3, n=100) >28 weeks to term. Results: The normal HbA(1c) reference interval for Caucasian non-pregnant women was 29-37 mmol\\/mol (Diabetes Control and Complications Trial; DCCT: 4.8%-5.5%), T1: 24-36 mmol\\/mol (DCCT: 4.3%-5.4%), T2: 25-35 mmol\\/mol (DCCT: 4.4%-5.4%) and T3: 28-39 mmol\\/mol (DCCT: 4.7%-5.7%). HbA(1c) was significantly decreased in trimesters 1 and 2 compared to non-pregnant women. Conclusions: HbA(1c) trimester-specific reference intervals are required to better inform the management of pregnancies complicated by diabetes.

  20. Radioisotope Characterization of HB Line Low Activity Waste

    International Nuclear Information System (INIS)

    Snyder, S.J.

    1999-01-01

    The purpose of this document is to provide a physical, chemical, hazardous and radiological characterization of Low-Level Waste (LLW) generated in HB-Line as required by the 1S Manual, Savannah River Site Waste Acceptance Criteria Manual

  1. Impact of demographics and disease progression on the relationship between glucose and HbA1c.

    Science.gov (United States)

    Claussen, Anetta; Møller, Jonas B; Kristensen, Niels R; Klim, Søren; Kjellsson, Maria C; Ingwersen, Steen H; Karlsson, Mats O

    2017-06-15

    Several studies have shown that the relationship between mean plasma glucose (MPG) and glycated haemoglobin (HbA1c) may vary across populations. Especially race has previously been referred to shift the regression line that links MPG to HbA1c at steady-state (Herman & Cohen, 2012). To assess the influence of demographic and disease progression-related covariates on the intercept of the estimated linear MPG-HbA1c relationship in a longitudinal model. Longitudinal patient-level data from 16 late-phase trials in type 2 diabetes with a total of 8927 subjects was used to study covariates for the relationship between MPG and HbA1c. The analysed covariates included age group, BMI, gender, race, diabetes duration, and pre-trial treatment. Differences between trials were taken into account by estimating a trial-to-trial variability component. Participants included 47% females and 20% above 65years. 77% were Caucasian, 9% were Asian, 5% were Black and the remaining 9% were analysed together as other races. Estimates of the change in the intercept of the MPG-HbA1c relationship due to the mentioned covariates were determined using a longitudinal model. The analysis showed that pre-trial treatment with insulin had the most pronounced impact associated with a 0.34% higher HbA1c at a given MPG. However, race, diabetes duration and age group also had an impact on the MPG-HbA1c relationship. Our analysis shows that the relationship between MPG and HbA1c is relatively insensitive to covariates, but shows small variations across populations, which may be relevant to take into account when predicting HbA1c response based on MPG measurements in clinical trials. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Discordance in the diagnosis of diabetes: Comparison between HbA1c and fasting plasma glucose.

    Science.gov (United States)

    Ho-Pham, Lan T; Nguyen, Uyen D T; Tran, Truong X; Nguyen, Tuan V

    2017-01-01

    HbA1c has been introduced as a complementary diagnostic test for diabetes, but its impact on disease prevalence is unknown. This study evaluated the concordance between HbA1c and fasting plasma glucose (FPG) in the diagnosis of diabetes in the general population. The study was designed as a population based investigation, with participants being sampled from the Ho Chi Minh City, Vietnam. Blood samples were collected after overnight fasting and analyzed within 4 hours after collection. HbA1c was measured with high pressure liquid chromatography (Arkray Adams, Japan). FPG was measured by the hexokinase method (Advia Autoanalyzer; Bayer Diagnostics, Germany). Diabetes was defined as HbA1c ≥ 6.5% or FPG ≥ 7.0 mmol/L. Prediabetes was classified as HbA1c between 5.7% and 6.4%. The study included 3523 individuals (2356 women) aged 30 years and above. Based on the HbA1c test, the prevalence of diabetes and prediabetes was 9.7% (95%CI, 8.7-10.7%; n = 342) and 34.6% (33.0-36.2; n = 1219), respectively. Based on the FPG test, the prevalence of diabetes and prediabetes was 6.3% (95%CI, 5.5-7.2%; n = 223) and 12.1% (11.1-13.2; n = 427). Among the 427 individuals identified by FPG as "pre-diabetes", 28.6% were classified as diabetes by HbA1c test. The weighted kappa statistic of concordance between HbA1c and FPG was 0.55, with most of the discordance being in the prediabetes group. These data indicate that there is a significant discordance in the diagnosis of diabetes between FPG and HbA1c measurements, and the discordance could have significant impact on clinical practice. FPG appears to underestimate the burden of undiagnosed diabetes.

  3. HB-Line Material Control and Accountability Measurements at SRS

    International Nuclear Information System (INIS)

    Casella, V.R.

    2003-01-01

    Presently, HB-Line work at the Savannah River Site consists primarily of the stabilization and packaging of nuclear materials for storage and the characterization of materials for disposition in H-Area. In order to ensure compliance with Material Control and Accountability (MC and A) Regulations, accountability measurements are performed throughout the HB-Line processes. Accountability measurements are used to keep track of the nuclear material inventory by constantly updating the amount of material in the MBAs (Material Balance Area) and sub-MBAs. This is done by subtracting the amount of accountable material that is added to a process and by adding the amount of accountable material that is put back in storage. A Physical Inventory is taken and compared to the ''Book Value'' listed in the Nuclear Material Accounting System. The difference (BPID) in the Book Inventory minus the Physical Inventory of a sub-account for bulk material must agree within the measurement errors combined in quadrature to provide assurance that nuclear material is accounted for. This work provides an overview of HB-Line processes and accountability measurements. The Scrap Recovery Line and Neptunium-237/Plutonium-239 Oxide Line are described and sampling and analyses for Phase II are provided. Recommendations for improvements are provided to improve efficiency and cost effectiveness

  4. Glutathione Redox System in β-Thalassemia/Hb E Patients

    Directory of Open Access Journals (Sweden)

    Ruchaneekorn W. Kalpravidh

    2013-01-01

    Full Text Available β-thalassemia/Hb E is known to cause oxidative stress induced by iron overload. The glutathione system is the major endogenous antioxidant that protects animal cells from oxidative damage. This study aimed to determine the effect of disease state and splenectomy on redox status expressed by whole blood glutathione (GSH/glutathione disulfide (GSSG and also to evaluate glutathione-related responses to oxidation in β-thalassemia/Hb E patients. Twenty-seven normal subjects and 25 β-thalassemia/Hb E patients were recruited and blood was collected. The GSH/GSSG ratio, activities of glutathione-related enzymes, hematological parameters, and serum ferritin levels were determined in individuals. Patients had high iron-induced oxidative stress, shown as significantly increased serum ferritin, a decreased GSH/GSSG ratio, and increased activities of glutathione-related enzymes. Splenectomy increased serum ferritin levels and decreased GSH levels concomitant with unchanged glutathione-related enzyme activities. The redox ratio had a positive correlation with hemoglobin levels and negative correlation with levels of serum ferritin. The glutathione system may be the body’s first-line defense used against oxidative stress and to maintain redox homeostasis in thalassemic patients based on the significant correlations between the GSH/GSSH ratio and degree of anemia or body iron stores.

  5. Defining a glycated haemoglobin (HbA1c) level that predicts increased risk of penile implant infection.

    Science.gov (United States)

    Habous, Mohamad; Tal, Raanan; Tealab, Alaa; Soliman, Tarek; Nassar, Mohammed; Mekawi, Zenhom; Mahmoud, Saad; Abdelwahab, Osama; Elkhouly, Mohamed; Kamr, Hatem; Remeah, Abdallah; Binsaleh, Saleh; Ralph, David; Mulhall, John

    2018-02-01

    To re-evaluate the role of diabetes mellitus (DM) as a risk factor for penile implant infection by exploring the association between glycated haemoglobin (HbA1c) levels and penile implant infection rates and to define a threshold value that predicts implant infection. We conducted a multicentre prospective study including all patients undergoing penile implant surgery between 2009 and 2015. Preoperative, perioperative and postoperative management were identical for the entire cohort. Univariate analysis was performed to define predictors of implant infection. The HbA1c levels were analysed as continuous variables and sequential analysis was conducted using 0.5% increments to define a threshold level predicting implant infection. Multivariable analysis was performed with the following factors entered in the model: DM, HbA1C level, patient age, implant type, number of vascular risk factors (VRFs), presence of Peyronie's disease (PD), body mass index (BMI), and surgeon volume. A receiver operating characteristic (ROC) curve was generated to define the optimal HbA1C threshold for infection prediction. In all, 902 implant procedures were performed over the study period. The mean patient age was 56.6 years. The mean HbA1c level was 8.0%, with 81% of men having a HbA1c level of >6%. In all, 685 (76%) implants were malleable and 217 (24%) were inflatable devices; 302 (33.5%) patients also had a diagnosis of PD. The overall infection rate was 8.9% (80/902). Patients who had implant infection had significantly higher mean HbA1c levels, 9.5% vs 7.8% (P HbA1c level, we found infection rates were: 1.3% with HbA1c level of 9.5% (P HbA1c level, whilst a high-volume surgeon had a protective effect and was associated with a reduced infection risk. Using ROC analysis, we determined that a HbA1c threshold level of 8.5% predicted infection with a sensitivity of 80% and a specificity of 65%. Uncontrolled DM is associated with increased risk of infection after penile implant surgery

  6. Formas moleculares da gonadotrofina coriônica humana: características, ensaios e uso clínico Molecular forms of human chorionic gonadotropin: characteristics, assays and clinical use

    Directory of Open Access Journals (Sweden)

    Sebastião Freitas de Medeiros

    2006-04-01

    Full Text Available A gonadotrofina coriônica humana (hCG é estruturada pela combinação não covalente de duas subunidades, alfa (alfahCG e beta (betahCG, sintetizadas separadamente pelo tecido trofoblástico normal, mola hidatiforme, coriocarcinoma, células hipofisárias e tecidos tumorais de diversos tipos histológicos. A síntese da cadeia peptídica e sua glicosilação na célula secretora envolve complexa ação de várias enzimas. Esta complexidade resulta na secreção de moléculas heterogêneas. As diferentes formas moleculares secretadas podem ser encontradas no soro, urina e líquido amniótico de gestantes; soro, urina e vesículas em pacientes com mola hidatiforme ou coriocarcinoma e em fluidos biológicos de mulheres não grávidas e homens normais ou acometidos de tumores de diferente origem embrionária. Tanto a molécula hCG nativa, intacta,como suas subunidades nas formas livres e as variantes hCG hiperglicosilada (H-hCG, hCG clivada (N-hCG e fragmento-núcleo de betahCG (CF-betahCG têm aplicabilidade clínica relevante. Dependendo da forma molecular mais prevalente ou da proporção da molécula variante/molécula hCG intacta numa determinada condição clínica, há indicação para a dosagem específica de uma ou mais destas moléculas. Este texto revê o conhecimento básico e analisa o uso da hCG e suas variantes na detecção precoce da gravidez ectópica ou gestantes em risco de abortamento, na identificação precoce de anomalias cromossômicas êmbrio-fetais e estima o risco da gestação de evoluir com pré-eclâmpsia ou crescimento intra-uterino restrito. Examina, ainda, fora da gravidez, o emprego destas moléculas como marcadores laboratoriais de tumores com diferentes tipos histológicos e seguimento após a terapia inicial. Conclui-se ser útil o uso da dosagem de hCG e suas moléculas variantes na prática clínica, mas a dificuldade no desenvolvimento e obtenção de ensaios mais sensíveis e específicos restringe a

  7. Significance of HbA1c and its measurement in the diagnosis of diabetes mellitus: US experience

    Directory of Open Access Journals (Sweden)

    Juarez DT

    2014-10-01

    Full Text Available Deborah Taira Juarez, Kendra M Demaris, Roy Goo, Christina Louise Mnatzaganian, Helen Wong SmithDaniel K Inouye College of Pharmacy, University of Hawaii at Hilo, Honolulu, HI, USAAbstract: The 2014 American Diabetes Association guidelines denote four means of diagnosing diabetes. The first of these is a glycosylated hemoglobin (HbA1c >6.5%. This literature review summarizes studies (n=47 in the USA examining the significance, strengths, and limitations of using HbA1c as a diagnostic tool for diabetes, relative to other available means. Due to the relatively recent adoption of HbA1c as a diabetes mellitus diagnostic tool, a hybrid systematic, truncated review of the literature was implemented. Based on these studies, we conclude that HbA1c screening for diabetes has been found to be convenient and effective in diagnosing diabetes. HbA1c screening is particularly helpful in community-based and acute care settings where tests requiring fasting are not practical. Using HbA1c to diagnose diabetes also has some limitations. For instance, HbA1c testing may underestimate the prevalence of diabetes, particularly among whites. Because this bias differs by racial group, prevalence and resulting estimates of health disparities based on HbA1c screening differ from those based on other methods of diagnosis. In addition, existing evidence suggests that HbA1c screening may not be valid in certain subgroups, such as children, women with gestational diabetes, patients with human immunodeficiency virus, and those with prediabetes. Further guidelines are needed to clarify the appropriate use of HbA1c screening in these populations.Keywords: diabetes mellitus, diagnosis, glycosylated hemoglobin, USA

  8. Clinical and hematological response to hydroxyurea in a patient with Hb Lepore/beta-thalassemia.

    Science.gov (United States)

    Rigano, P; Manfré, L; La Galla, R; Renda, D; Renda, M C; Calabrese, A; Calzolari, R; Maggio, A

    1997-05-01

    The possibility of increasing Hb F in vivo using drugs like 5-azacytidine, hydroxyurea, and butyrate has been established. However, in many cases this does not entail an increase in total hemoglobin. We report on a patient with Hb Lepore/beta-thalassemia being treated with hydroxyurea (30 mg/Kg/day) because of the presence of erythroid extramedullary masses with severe neurological abnormalities. During therapy the patient showed a remarkable improvement in neurological signs due to the reduction in extra-medullary masses, a significant increase in both total hemoglobin (from 5.8 to 9.7 g/dl) and Hb F (from 4.9 g/dl to 9.1 g/dl). The marked improvement in hemoglobin level in our patient with Hb Lepore/beta-thalassemia suggests gamma-globin gene activation due to the DNA structure determined by the crossover event.

  9. Hb Heathrow [β103(G5)Phe→Leu], a First Report in an Asian Patient with Erythrocytosis.

    Science.gov (United States)

    Shin, Sang Yong; Kim, Hyun Young; Kim, Hee Jin; Kim, Hoon Gu

    2017-05-01

    Congenital erythrocytosis (CE) is a rare and heterogeneous disease. The high oxygen affinity hemoglobin (Hb) variants are the most common cause of CE. Herein, we report a Korean patient with isolated erythrocytosis. A 25-year-old man was referred to our hospital for evaluation of high Hb level (Hb 20.4 g/dL, hematocrit 58%, reticulocyte count 2.90%, white blood cell count 6.83×10⁹/L, and platelet count 195×10⁹/L). Bone marrow biopsy revealed normocellular marrow without myeloproliferative features. JAK2 (V617F, exon 12), CALR (exon 9), and MPL W515K/L mutations were not detected. P₅₀ (partial pressure at which Hb is half saturated with oxygen), which is an indicator of left-shift of oxygen dissociation curve (high oxygen affinity state), was 14.3 mm Hg (reference value 22.6-29.4 mm Hg). He was suspected to have CE. Mutation analysis of the HBB gene revealed the known Hb variant, Hb Heathrow [β103(G5)Phe→Leu]. This is the first report of Hb Heathrow in Asian. © Copyright: Yonsei University College of Medicine 2017.

  10. Effects of common hemoglobin variants on HbA1c measurements in China: results for α- and β-globin variants measured by six methods.

    Science.gov (United States)

    Xu, Anping; Chen, Weidong; Xia, Yong; Zhou, Yu; Ji, Ling

    2018-04-07

    HbA1c is a widely used biomarker for diabetes mellitus management. Here, we evaluated the accuracy of six methods for determining HbA1c values in Chinese patients with common α- and β-globin chains variants in China. Blood samples from normal subjects and individuals exhibiting hemoglobin variants were analyzed for HbA1c, using Sebia Capillarys 2 Flex Piercing (C2FP), Bio-Rad Variant II Turbo 2.0, Tosoh HLC-723 G8 (ver. 5.24), Arkray ADAMS A1c HA-8180V fast mode, Cobas c501 and Trinity Ultra2 systems. DNA sequencing revealed five common β-globin chain variants and three common α-globin chain variants. The most common variant was Hb E, followed by Hb New York, Hb J-Bangkok, Hb G-Coushatta, Hb Q-Thailand, Hb G-Honolulu, Hb Ube-2 and Hb G-Taipei. Variant II Turbo 2.0, Ultra2 and Cobas c501 showed good agreement with C2FP for most samples with variants. HLC-723 G8 yielded no HbA1c values for Hb J-Bangkok, Hb Q-Thailand and Hb G-Honolulu. Samples with Hb E, Hb G-Coushatta, Hb G-Taipei and Hb Ube-2 produced significant negative biases for HLC-723 G8. HA-8180V showed statistically significant differences for Hb E, Hb G-Coushatta, Hb G-Taipei, Hb Q-Thailand and Hb G-Honolulu. HA-8180V yielded no HbA1c values for Hb J-Bangkok. All methods showed good agreement for samples with Hb New York. Some common hemoglobin variants can interfere with HbA1c determination by the most popular methods in China.

  11. Chronic cerebral hypoperfusion-induced impairment of Aβ clearance requires HB-EGF-dependent sequential activation of HIF1α and MMP9.

    Science.gov (United States)

    Ashok, Anushruti; Rai, Nagendra Kumar; Raza, Waseem; Pandey, Rukmani; Bandyopadhyay, Sanghamitra

    2016-11-01

    Chronic cerebral hypoperfusion (CCH) manifests Alzheimer's Disease (AD) neuropathology, marked by increased amyloid beta (Aβ). Besides, hypoxia stimulates Heparin-binding EGF-like growth factor (HB-EGF) mRNA expression in the hippocampus. However, involvement of HB-EGF in CCH-induced Aβ pathology remains unidentified. Here, using Bilateral Common Carotid Artery Occlusion mouse model, we explored the mechanism of HB-EGF regulated Aβ induction in CCH. We found that HB-EGF inhibition suppressed, while exogenous-HB-EGF triggered hippocampal Aβ, proving HB-EGF-dependent Aβ increase. We also detected that HB-EGF affected the expression of primary Aβ transporters, receptor for advanced glycation end-products (RAGE) and lipoprotein receptor-related protein-1 (LRP-1), indicating impaired Aβ clearance across the blood-brain barrier (BBB). An HB-EGF-dependent loss in BBB integrity supported impaired Aβ clearance. The effect of HB-EGF on Amyloid Precursor Protein pathway was relatively insignificant, suggesting a lesser effect on Aβ generation. Delving into BBB disruption mechanism demonstrated HB-EGF-mediated stimulation of Matrix metalloprotease-9 (MMP9), which affected BBB via HB-EGF-ectodomain shedding and epidermal growth factor receptor activation. Examining the intersection of HB-EGF-regulated pathway and hypoxia revealed HB-EGF-dependent increase in transcription factor, Hypoxia-inducible factor-1alpha (HIF1α). Further, via binding to hypoxia-responsive elements in MMP9 gene, HIF1α stimulated MMP9 expression, and therefore appeared as a prominent intermediary in HB-EGF-induced BBB damage. Overall, our study reveals the essential role of HB-EGF in triggering CCH-mediated Aβ accumulation. The proposed mechanism involves an HB-EGF-dependent HIF1α increase, generating MMP9 that stimulates soluble-HB-EGF/EGFR-induced BBB disintegration. Consequently, CCH-mediated hippocampal RAGE and LRP-1 deregulation together with BBB damage impair Aβ transport and clearance

  12. The glyoxysomal and plastid molecular chaperones (70-kDa heat shock protein) of watermelon cotyledons are encoded by a single gene

    NARCIS (Netherlands)

    Wimmer, Bernhard; Lottspeich, Friedrich; Klei, Ida van der; Veenhuis, Marten; Gietl, Christine

    1997-01-01

    The monoclonal a-70-kDa heat shock protein (hsp70) antibody recognizes in crude extracts from watermelon (Citrullus vulgaris) cotyledons with molecular masses of 70 and 72 KDa, Immunocytochemistry on watermelon cotyledon tissue and on isolated glyoxysomes identified hsp70s in the matrix of

  13. Translating HbA1c measurements into estimated average glucose values in pregnant women with diabetes.

    Science.gov (United States)

    Law, Graham R; Gilthorpe, Mark S; Secher, Anna L; Temple, Rosemary; Bilous, Rudolf; Mathiesen, Elisabeth R; Murphy, Helen R; Scott, Eleanor M

    2017-04-01

    This study aimed to examine the relationship between average glucose levels, assessed by continuous glucose monitoring (CGM), and HbA 1c levels in pregnant women with diabetes to determine whether calculations of standard estimated average glucose (eAG) levels from HbA 1c measurements are applicable to pregnant women with diabetes. CGM data from 117 pregnant women (89 women with type 1 diabetes; 28 women with type 2 diabetes) were analysed. Average glucose levels were calculated from 5-7 day CGM profiles (mean 1275 glucose values per profile) and paired with a corresponding (±1 week) HbA 1c measure. In total, 688 average glucose-HbA 1c pairs were obtained across pregnancy (mean six pairs per participant). Average glucose level was used as the dependent variable in a regression model. Covariates were gestational week, study centre and HbA 1c . There was a strong association between HbA 1c and average glucose values in pregnancy (coefficient 0.67 [95% CI 0.57, 0.78]), i.e. a 1% (11 mmol/mol) difference in HbA 1c corresponded to a 0.67 mmol/l difference in average glucose. The random effects model that included gestational week as a curvilinear (quadratic) covariate fitted best, allowing calculation of a pregnancy-specific eAG (PeAG). This showed that an HbA 1c of 8.0% (64 mmol/mol) gave a PeAG of 7.4-7.7 mmol/l (depending on gestational week), compared with a standard eAG of 10.2 mmol/l. The PeAG associated with maintaining an HbA 1c level of 6.0% (42 mmol/mol) during pregnancy was between 6.4 and 6.7 mmol/l, depending on gestational week. The HbA 1c -average glucose relationship is altered by pregnancy. Routinely generated standard eAG values do not account for this difference between pregnant and non-pregnant individuals and, thus, should not be used during pregnancy. Instead, the PeAG values deduced in the current study are recommended for antenatal clinical care.

  14. Improving access to HbA1c in sub-Saharan Africa (IA3) cohort: cohort profile.

    Science.gov (United States)

    Balde, Naby; Camara, Alioune; Sobngwi-Tambekou, Joelle; Balti, Eric Vounsia; Tchatchoua, Alain; Fezeu, Leopold; Limen, Serge; Ngamani, Sylvie; Ngapout, Suzanne; Kengne, Andre Pascal; Sobngwi, Eugene

    2017-01-01

    Glycated haemoglobin (HbA1c) is the best surrogate of average blood glucose control in diabetic patients, and lowering HbA1c significantly reduces diabetes complications. Moreover, immediate feedback of HbA1c measurement to patients may improve control. However, HbA1c is unavailable in most parts of Africa, a continent with one of the highest burden of diabetes. To translate these evidences, we are conducting a multicentric project in 10 health care facilities in Guinea and Cameroon to evaluate the feasibility and one-year benefit of affordable HbA1c measurement with immediate feedback to patients on diabetes control and related outcomes. We consecutively enrolled patients with diabetes mellitus independently of the type of disease. We hypothesised an average 1%-decrease in HbA1c in a 1000-patient study population, with a 20% increase in the number of patients reaching treatment goals within 12 months of intervention and follow-up. A total of 1, 349 diabetic patients aged 56.2±12.6 years are enrolled (813 in Cameroon and 536 in Guinea) of whom 59.8% are women. The mean duration of diabetes is 7.4±6.3 years and baseline HbA1c is 9.7±2.6% in Guinea and 8.6±2.5% in Cameroon. To investigate whether the introduction of routine HbA1c measurement with immediate feedback to patients and provision of relevant education would improve diabetes control after one year. The impact of the intervention on diabetes associated-complications and mortality warrant further assessment in the long term.

  15. Oxidized LDL but not total LDL is associated with HbA1c in individuals without diabetes.

    Science.gov (United States)

    Spessatto, Débora; Brum, Liz Marina Bueno Dos Passos; Camargo, Joíza Lins

    2017-08-01

    This study investigates the association between HbA1c, LDL and oxi-LDL in individuals without diabetes (DM). One hundred and ninety-six individuals, without DM, were enrolled and divided into three groups according to HbA1c and fasting plasma glucose values. HbA1c, oxi-LDL, LDL, and other biochemical measurements of lipid profile were also carried out. oxi-LDL levels showed significant differences among all groups and group 3 presented higher values [34U/L (27-46); 44U/L (37-70); and 86U/L (49-136); pHbA1c showed moderate positive associations with oxi-LDL (r=0.431; pHbA1c and TC (r=0.142; p=0.048), triglycerides (r=0.155; p=0.030), LDL (r=0.148; p=0.039), non-HDL (r=0.192; p=0.007) and Apo B (r=0.171, pHbA1c and oxi-LDL, oxi-LDL/HDL and oxi-LDL/LDL ratios remained significant even after adjustment by multiple linear regression analysis for the variables alcohol consumption, use of medicine, BMI, and age. oxi-LDL levels are significantly associated with HbA1c in non-diabetic individuals. However, the levels of traditional atherogenic lipids only showed a weak association with HbA1c levels. Those at high risk of developing DM or cardiovascular disease have higher levels of oxi-LDL. These data favor to the use of HbA1c as a biomarker to identify individuals at risk of developing complications even in non-diabetic glycemic levels. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Aldimine Formation Reaction, the First Step of the Maillard Early-phase Reaction, Might be Enhanced in Variant Hemoglobin, Hb Himeji.

    Science.gov (United States)

    Koga, Masafumi; Inada, Shinya; Shimizu, Sayoko; Hatazaki, Masahiro; Umayahara, Yutaka; Nishihara, Eijun

    2015-01-01

    Hb Himeji (β140Ala→Asp) is known as a variant hemoglobin in which glycation is enhanced and HbA1c measured by immunoassay shows a high value. The phenomenon of enhanced glycation in Hb Himeji is based on the fact that the glycation product of variant hemoglobin (HbX1c) shows a higher value than HbA1c. In this study, we investigated whether aldimine formation reaction, the first step of the Maillard early-phase reaction, is enhanced in Hb Himeji in vitro. Three non-diabetic subjects with Hb Himeji and four non-diabetic subjects without variant hemoglobin were enrolled. In order to examine aldimine formation reaction, whole blood cells were incubated with 500 mg/dl of glucose at 37°C for 1 hour and were analyzed by high-performance liquid chromatography. Both HbA1c and HbX1c were not increased in this condition. After incubation with glucose, labile HbA1c (LA1c) fraction increased in the controls (1.1±0.3%). In subjects with Hb Himeji increases in the labile HbX1c (LX1c) fraction as well as the LA1c fraction were observed, and the degree of increase in the LX1c fraction was significantly higher than that of the LA1c fraction (1.8±0.1% vs. 0.5±0.2%, Preaction might be enhanced in Hb Himeji in vitro. The 140th amino acid in β chain of hemoglobin is suggested to be involved in aldimine formation reaction. © 2015 by the Association of Clinical Scientists, Inc.

  17. Role of HbA1c in the Screening of Diabetes Mellitus in a Korean Rural Community

    Directory of Open Access Journals (Sweden)

    Jae Hyun Kim

    2012-02-01

    Full Text Available BackgroundRecently, the measurement of glycated hemoglobin (HbA1c was recommended as an alternative to fasting plasma glucose or oral glucose tolerance tests for diagnosing diabetes mellitus (DM. In this study, we analyzed HbA1c levels for diabetes mellitus screening in a Korean rural population.MethodsWe analyzed data from 10,111 subjects from a Korean Rural Genomic Cohort study and generated a receiver operating characteristic curve to determine an appropriate HbA1c cutoff value for diabetes.ResultsThe mean age of the subjects was 56.3±8.1 years. Fasting plasma glucose and 2-hour plasma glucose after 75 g oral glucose tolerance tests were 97.5±25.6 and 138.3±67.1 mg/dL, respectively. The mean HbA1c level of the subjects was 5.7±0.9%. There were 8,809 non-DM patients (87.1% and 1,302 DM patients (12.9%. A positive relationship between HbA1c and plasma glucose levels and between HbA1c and 2-hour plasma glucose levels after oral glucose tolerance tests was found in a scatter plot of the data. Using Youden's index, the proper cutoff level of HbA1c for diabetes mellitus screening was 5.95% (sensitivity, 77%; specificity, 89.4%.ConclusionOur results suggest that the optimal HbA1c level for DM screening is 5.95%.

  18. Characterization of Hb Bart's Hydrops Fetalis Caused by - -SEA and a Large Novel α0-Thalassemia Deletion.

    Science.gov (United States)

    He, Sheng; Li, Jihui; Huang, Peng; Zhang, Shujie; Lin, Li; Zuo, Yangjin; Tian, Xiaoxian; Zheng, Chenguang; Qiu, Xiaoxia; Chen, Biyan

    2018-01-01

    Hb Bart's hydrops fetalis is the most severe and generally fatal clinical phenotype of α-thalassemia (α-thal), which is due to the deletion of all four functional α-globin genes of hemoglobin (Hb), resulting in no α-globin chain production (- -/- -). Homozygosity for the - - SEA (Southeast Asian) α-globin gene deletion is the main cause of the Hb Bart's hydrops fetalis in Asia, especially South China. Occasionally, other α 0 -thal deletions can also be found. In this study, we report a case with an atypical form of Hb Bart's hydrops fetalis that was caused by - - SEA and a large novel α 0 -thal deletion (- - GX ) (Guangxi). The fetus with Hb Bart's in our study presented fetal hydrops features in early gestation which was different from that of traditional Hb Bart's hydrops fetalis with a homozygous - - SEA deletion. The early onset of fetal hydrops is attributed to the decreased formation of embryonic Hb Portland (ζ2γ2), which is proposed as a candidate for reactivation in cases of severe α-thal. Our findings indicated that it was important to characterize new or rare mutations, and highlighted the significance of using ultrasonography to identify signs of Hb Bart's hydrops fetalis.

  19. Effect of occasional epoetin use in combination with a stable darbepoetin dosage on anemia management in hemodialysis patients

    Directory of Open Access Journals (Sweden)

    Shimamatsu K

    2014-12-01

    Full Text Available Kazumasa Shimamatsu Shimamatsu Naika Iin (Clinic, Shiseikai Medical Corporation, Chikushino City, Japan Aim: Taking advantage of the characteristics of both darbepoetin (DA and epoetin (EPO might be a reasonable option for stabilizing hemoglobin (Hb control in hemodialysis (HD patients. The effect of DA assisted by EPO (DA/EPO on Hb control was evaluated retrospectively in comparison with that of EPO monotherapy. Methods: Twenty-six HD patients whose annual mean Hb values were available for both an EPO monotherapy period and a DA/EPO period were selected for analysis. During the DA/EPO period, DA was given on the second HD day of a week, and EPO was given if needed on the first and third HD days. Under stable DA dosage, when Hb rose >12 g/dL, EPO was eliminated. When Hb decreased <10 g/dL, EPO was added again. The variability of annual mean Hb values from the 26 HD patients during the DA/EPO period was compared with that during the EPO period. Additionally, the distance in Hb (d-Hb; absolute value of difference between the annual mean Hb values and the target Hb (11 g/dL during the DA/EPO period was compared with that during the EPO period. Results: The variability of annual mean Hb values during the DA/EPO period was significantly smaller than that during the EPO period (11.2±0.25 g/dL versus [vs] 11.0±0.50 g/dL; the F-test for equality of variance, P<0.001. Additionally, the d-Hb during the DA/EPO period was significantly smaller than that during the EPO period (0.22±0.21 g/dL vs 0.38±0.31 g/dL, P<0.03. The total doses (as EPO equivalents of DA with EPO were reduced to 82.2% of the baseline EPO dose during the EPO monotherapy period. The expenditure for the DA/EPO period was significantly reduced to 80.9% of that for the EPO monotherapy. Also, the annual total amount of intravenous iron supplementation during the DA/EPO period was significantly reduced compared with that during the EPO period (546±304 mg/year vs 684±314 mg/year, P<0

  20. Environmental regulation of lateral root emergence in Medicago truncatula requires the HD-Zip I transcription factor HB1.

    Science.gov (United States)

    Ariel, Federico; Diet, Anouck; Verdenaud, Marion; Gruber, Véronique; Frugier, Florian; Chan, Raquel; Crespi, Martin

    2010-07-01

    The adaptation of root architecture to environmental constraints is a major agricultural trait, notably in legumes, the third main crop worldwide. This root developmental plasticity depends on the formation of lateral roots (LRs) emerging from primary roots. In the model legume Medicago truncatula, the HD-Zip I transcription factor HB1 is expressed in primary and lateral root meristems and induced by salt stress. Constitutive expression of HB1 in M. truncatula roots alters their architecture, whereas hb1 TILLING mutants showed increased lateral root emergence. Electrophoretic mobility shift assay, promoter mutagenesis, and chromatin immunoprecipitation-PCR assays revealed that HB1 directly recognizes a CAATAATTG cis-element present in the promoter of a LOB-like (for Lateral Organ Boundaries) gene, LBD1, transcriptionally regulated by auxin. Expression of these genes in response to abscisic acid and auxin and their behavior in hb1 mutants revealed an HB1-mediated repression of LBD1 acting during LR emergence. M. truncatula HB1 regulates an adaptive developmental response to minimize the root surface exposed to adverse environmental stresses.

  1. Implantation of FRAPCON-2 code in HB computer

    International Nuclear Information System (INIS)

    Silva, C.F. da.

    1987-05-01

    The modifications carried out for implanting FRAPCON-2 computer code in the HB DPS-T7 computer are presented. The FRAPCON-2 code calculates thermo-mechanical response during long period of burnup in stationary state for fuel rods of PWR type reactors. (M.C.K.)

  2. Enzymatic and acidic degradation of high molecular weight dextran into low molecular weight and its characterizations using novel Diffusion-ordered NMR spectroscopy.

    Science.gov (United States)

    Iqbal, Samina; Marchetti, Roberta; Aman, Afsheen; Silipo, Alba; Qader, Shah Ali Ul; Molinaro, Antonio

    2017-10-01

    Low molecular weight fractions were derived from native high molecular weight dextran produced by Leuconostoc mesenteroides KIBGE-IB26. Structural characterization of native and low molecular weight fractions obtained after acidic and enzymatic hydrolysis was done using FTIR and NMR spectroscopy. The molecular weight was estimated using Diffusion Ordered NMR spectroscopy. Native dextran (892kDa) is composed of α-(1→6) glycosidic linkage along with α-(1→3) branching. Major proportion of 528kDa dextran was obtained after prolong enzymatic hydrolysis however, an effective acidic treatment at pH-1.4 up to 02 and 04h of exposure resulted in the formation of 77kDa and 57kDa, respectively. The increment in pH from 1.4 to 1.8 lowered the hydrolysis efficiency and resulted in the formation of 270kDa dextran fraction. The results suggest that derived low molecular weight water soluble fractions can be utilized as a drug delivery carrier along with multiple application relating pharmaceutical industries. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Acute Sickle Hepatic Crisis after Liver Transplantation in a Patient with Hb SC Disease

    Directory of Open Access Journals (Sweden)

    J. H. Gillis

    2015-01-01

    Full Text Available Acute sickle hepatic crisis (ASHC has been observed in approximately 10% of patients with sickle cell disease. It occurs predominantly in patients with homozygous (Hb SS sickle cell anemia and to a lesser degree in patients with Hb SC disease, sickle cell trait, and Hb S beta thalassemia. Patients commonly present with jaundice, right upper quadrant pain, nausea, low-grade fever, tender hepatomegaly, and mild to moderate elevations in serum AST, ALT, and bilirubin. We describe the case of a patient with a history of hemoglobin SC disease and cirrhosis caused by hepatitis C presenting approximately 1 year after liver transplantation with an ASHC. The diagnosis was confirmed by liver biopsy. Our patient was treated with RBC exchange transfusions, IV hydration, and analgesia and made a complete recovery. Only a limited number of patients with sickle cell disease have received liver transplants, and, to our knowledge, this is the first case of ASHC after transplantation in a patient with Hb SC disease.

  4. Rubber particle proteins, HbREF and HbSRPP, show different interactions with model membranes.

    Science.gov (United States)

    Berthelot, Karine; Lecomte, Sophie; Estevez, Yannick; Zhendre, Vanessa; Henry, Sarah; Thévenot, Julie; Dufourc, Erick J; Alves, Isabel D; Peruch, Frédéric

    2014-01-01

    The biomembrane surrounding rubber particles from the hevea latex is well known for its content of numerous allergen proteins. HbREF (Hevb1) and HbSRPP (Hevb3) are major components, linked on rubber particles, and they have been shown to be involved in rubber synthesis or quality (mass regulation), but their exact function is still to be determined. In this study we highlighted the different modes of interactions of both recombinant proteins with various membrane models (lipid monolayers, liposomes or supported bilayers, and multilamellar vesicles) to mimic the latex particle membrane. We combined various biophysical methods (polarization-modulation-infrared reflection-adsorption spectroscopy (PM-IRRAS)/ellipsometry, attenuated-total reflectance Fourier-transform infrared (ATR-FTIR), solid-state nuclear magnetic resonance (NMR), plasmon waveguide resonance (PWR), fluorescence spectroscopy) to elucidate their interactions. Small rubber particle protein (SRPP) shows less affinity than rubber elongation factor (REF) for the membranes but displays a kind of "covering" effect on the lipid headgroups without disturbing the membrane integrity. Its structure is conserved in the presence of lipids. Contrarily, REF demonstrates higher membrane affinity with changes in its aggregation properties, the amyloid nature of REF, which we previously reported, is not favored in the presence of lipids. REF binds and inserts into membranes. The membrane integrity is highly perturbed, and we suspect that REF is even able to remove lipids from the membrane leading to the formation of mixed micelles. These two homologous proteins show affinity to all membrane models tested but neatly differ in their interacting features. This could imply differential roles on the surface of rubber particles. © 2013.

  5. Validation and determination of a reference interval for canine HbA1c using an immunoturbidimetric assay.

    Science.gov (United States)

    Goemans, Anne F; Spence, Susanna J; Ramsey, Ian K

    2017-06-01

    Hemoglobin A1c (HbA1c) provides a reliable measure of glycemic control over 2-3 months in human diabetes mellitus. In dogs, presence of HbA1c has been demonstrated, but there are no validated commercial assays. The purpose of the study was to validate a commercially available automated immunoturbidimetric assay for canine HbA1c and determine an RI in a hospital population. The specificity of the assay was assessed by inducing glycosylation in vitro using isolated canine hemoglobin, repeatability by measuring canine samples 5 times in succession, long term inter-assay imprecision by measuring supplied control materials, stability using samples stored at 4°C over 5 days and -20°C over 8 weeks, linearity by mixing samples of known HbA1c in differing proportions, and the effect of anticoagulants with paired samples. An RI was determined using EDTA-anticoagulated blood samples from 60 nondiabetic hospitalized animals of various ages and breeds. Hemoglobin A1c was also measured in 10 diabetic dogs. The concentration of HbA1c increased proportionally with glucose concentration in vitro. For repeat measurements, the CV was 4.08% (range 1.16-6.10%). Samples were stable for 5 days at 4°C. The assay was linear within the assessed range. Heparin- and EDTA-anticoagulated blood provided comparable results. The RI for HbA1c was 9-18.5 mmol/mol. There was no apparent effect of age or breed on HbA1c. In diabetic dogs, HbA1c ranged from 14 to 48 mmol/mol. The assay provides a reliable method for canine HbA1c measurement with good analytic performance. © 2017 American Society for Veterinary Clinical Pathology.

  6. Prevalência de hemoglobinas anormais em recém-nascidos da cidade de Natal, Rio Grande do Norte, Brasil Prevalence of abnormal hemoglobins in newborns in Natal, Rio Grande do Norte, Brazil

    Directory of Open Access Journals (Sweden)

    Maria Cristina Pignataro Emerenciano de Araújo

    2004-02-01

    Full Text Available As hemoglobinopatias estão incluídas dentre as doenças hereditárias mais freqüentes nas populações humanas. Estudos realizados em diferentes regiões do Brasil têm demonstrado que as hemoglobinas anormais S e C são as mais prevalentes. Com o objetivo de investigar a prevalência de hemoglobinas anormais no período neonatal, foram analisadas 1.940 amostras de sangue de cordão umbilical provenientes de recém-nascidos de três maternidades da cidade de Natal, Rio Grande do Norte. Todas as amostras foram submetidas à eletroforese de hemoglobina em acetato de celulose utilizando tampão Tris-EDTA-Borato pH 8,5. As amostras que apresentaram hemoglobinas anormais foram submetidas à eletroforese em gel de ágar pH 6,2 para confirmação. Foram identificadas 37 (1,91% amostras com hemoglobinas anormais, das quais 29 (1,50% com traço falciforme (Hb FAS, 06 (0,31 % com Hb C, uma (0,05 % com anemia falciforme (Hb FS e uma (0,05 % apresentou Hb Bart's, sugerindo alfa talassemia. Os resultados encontrados evidenciam a necessidade de implantação da triagem de hemoglobinopatias em recém-nascidos na nossa população.Hemoglobinopathies are among the most prevalent hereditary diseases in humans. Studies in different areas of Brazil have identified the prevalence of S and C abnormal hemoglobins. The study analyzed 1,940 cord blood samples of newborns from maternity hospitals in Natal, Rio Grande do Norte State, to investigate the prevalence of abnormal hemoglobins. All samples were submitted to cellulose acetate electrophoresis using a Tris-EDTA-borate buffer at pH 8.5. Electrophoresis in agar gel pH 6.2 was performed on samples presenting abnormal hemoglobin. Some 37 (1.91% of the newborns presented hemoglobinopathies, as follows: 29 (1.50% sickle cell trait (Hb FAS, 6 (0.31% heterozygous Hb C (Hb FAC, one (0.05% homozygous Hb S (Hb FS, and one (0.05% Hb Barts suggestive of alpha thalassemia. The results show the need to implement screening for

  7. Docking molecular de derivados de 2-fenilindano-1,3-dionas inibidores da enzima HMG-CoA

    Directory of Open Access Journals (Sweden)

    R. Q. Pordeus

    2014-11-01

    Full Text Available As doenças cardiovasculares constituem uma das principais causas de mortes em todo o mundo. Estudos mostram que a enzima HMG-CoA é considerada uma precursora da via metabólica hipolipidêmica no soro sanguíneo. Na busca por uma nova classe de compostos aptos a inibir esta enzima e consequentemente reduzir os níveis de colesterol, as 2-fenilindano-1,3-dionas apresentam resultados promissores. Uma das maneiras de avaliar o poder farmacológico destes compostos e predizer análogos ainda mais potentes consiste na avaliação da interação entre fármaco (2-fenilindano-1,3-diona e enzima (HMG-CoA, em que se utiliza da técnica de modelagem molecular docking. Neste estudo, o procedimento computacional para obtenção dos resultados de docking foi feito através do software AutoDock 1.5.6. Para avaliar a interação no sítio ativo da HMG-CoA, utilizamos, dentre a série de congêneres, o composto 2-(2-clorofenilindano-1,3-diona. De acordo com os resultados obtidos, foi identificada uma interação hidrofílica importante, do tipo ligação de hidrogênio C=O∙∙∙H–N, a qual apresenta uma distância de 1.62 Å entre os grupos carbonila do anel diona e o aminoácido metionina da HMG-CoA. Outra ligação de hidrogênio p∙∙∙H–N com distância de 3.10 Å formada entre o anel aromático do grupo indano-1,3-diona e o aminoácido glicina também foi identificada.

  8. Insulin induces a transcriptional activation of epiregulin, HB-EGF and amphiregulin, by a PI3K-dependent mechanism: Identification of a specific insulin-responsive promoter element

    International Nuclear Information System (INIS)

    Ornskov, Dorthe; Nexo, Ebba; Sorensen, Boe S.

    2007-01-01

    Previously we have shown that insulin-stimulation of RT4 bladder cancer cells leads to increased proliferation, which require HER1 activation, and is accompanied by increased mRNA expression of the EGF-ligands heparin-binding EGF-like growth factor (HB-EGF), amphiregulin (AR), and epiregulin (EPI) [D. Ornskov, E. Nexo, B.S. Sorensen, Insulin-induced proliferation of bladder cancer cells is mediated through activation of the epidermal growth factor system, FEBS J. 273 (2006) 5479-5489]. In the present paper, we have investigated the molecular mechanism leading to this insulin-induced expression. We monitored the decay of mRNA after inhibiting transcription with Actinomycin D and demonstrated that the insulin-mediated increase was not caused by enhanced mRNA stability. In untreated cells, HB-EGF mRNA was the least stable, whereas AR and EPI mRNA decayed with slower kinetics. However, promoter analysis of HB-EGF and EPI demonstrated that insulin stimulated transcription. Studies on the EPI promoter identified the insulin-responsive element to be located in the region -564 to -365 bp. This region contains potential binding sites for the transcription factors SP1, AP1, and NF-κB. Interestingly, all three transcription factors can be activated by PI3K. We demonstrate that the insulin-induced expression of HB-EGF, AR, and EPI mRNA is completely prevented by the specific PI3K inhibitor Wortmannin, suggesting an involvement of the PI3K

  9. Thermo-mechanical model optimization of HB-LED packaging

    NARCIS (Netherlands)

    Yuan, C.A.; Erinc, M.; Gielen, A.W.J.; Waal, A. van der; Driel, W. van; Zhang, K.

    2011-01-01

    Lighting is an advancing phenomenon both on the technology and on the market level due to the rapid development of the solid state lighting technology. The efforts in improving the efficacy of high brightness LED's (HB-LED) have concentrated on the packaging architecture. Packaging plays a

  10. The Fallacy of Average: How Using HbA1c Alone to Assess Glycemic Control Can Be Misleading.

    Science.gov (United States)

    Beck, Roy W; Connor, Crystal G; Mullen, Deborah M; Wesley, David M; Bergenstal, Richard M

    2017-08-01

    HbA 1c is a v aluable metric for comparing treatment groups in a randomized trial, for assessing glycemic trends in a population over time, or for cross-sectional comparisons of glycemic control in different populations. However, what is not widely appreciated is that HbA 1c may not be a good indicator of an individual patient's glycemic control because of the wide range of mean glucose concentrations and glucose profiles that can be associated with a given HbA 1c level. To illustrate this point, we plotted mean glucose measured with continuous glucose monitoring (CGM) versus central laboratory-measured HbA 1c in 387 participants in three randomized trials, showing that not infrequently HbA 1c may underestimate or overestimate mean glucose, sometimes substantially. Thus, if HbA 1c is to be used to assess glycemic control, it is imperative to know the patient's actual mean glucose to understand how well HbA 1c is an indicator of the patient's glycemic control. With knowledge of the mean glucose, an estimated HbA 1c (eA1C) can be calculated with the formula provided in this article to compare with the measured HbA 1c . Estimating glycemic control from HbA 1c alone is in essence applying a population average to an individual, which can be misleading. Thus, a patient's CGM glucose profile has considerable value for optimizing his or her diabetes management. In this era of personalized, precision medicine, there are few better examples with respect to the fallacy of applying a population average to a specific patient rather than using specific information about the patient to determine the optimal approach to treatment. © 2017 by the American Diabetes Association.

  11. Baseline HbA1c to Identify High-Risk Gestational Diabetes: Utility in Early vs Standard Gestational Diabetes.

    Science.gov (United States)

    Sweeting, Arianne N; Ross, Glynis P; Hyett, Jon; Molyneaux, Lynda; Tan, Kris; Constantino, Maria; Harding, Anna Jane; Wong, Jencia

    2017-01-01

    The increasing prevalence of gestational diabetes mellitus (GDM) necessitates risk stratification directing limited antenatal resources to those at greatest risk. Recent evidence demonstrates that an early pregnancy glycated hemoglobin (HbA1c ≥5.9% (41 mmol/mol) predicts adverse pregnancy outcomes. To determine the optimal HbA1c threshold for adverse pregnancy outcomes in GDM in a treated multiethnic cohort and whether this differs in women diagnosed HbA1c (single-laboratory) measurement at the time of GDM diagnosis. Maternal clinical and pregnancy outcome data were collected prospectively. The association between baseline HbA1c and adverse pregnancy outcomes in early vs standard GDM. HbA1c was measured at a median of 17.6 ± 3.3 weeks' gestation in early GDM (n = 844) and 29.4 ± 2.6 weeks' gestation in standard GDM (n = 2254). In standard GDM, HbA1c >5.9% (41 mmol/mol) was associated with the greatest risk of large-for-gestational-age (odds ratio [95% confidence interval] = 2.7 [1.5-4.9]), macrosomia (3.5 [1.4-8.6]), cesarean section (3.6 [2.1-6.2]), and hypertensive disorders (2.6 [1.1-5.8]). In early GDM, similar HbA1c associations were seen; however, lower HbA1c correlated with the greatest risk of small-for-gestational-age (P trend = 0.004) and prevalence of neonatal hypoglycemia. Baseline HbA1c >5.9% (41 mmol/mol) identifies an increased risk of large-for-gestational-age, macrosomia, cesarean section, and hypertensive disorders in standard GDM. Although similar associations are seen in early GDM, higher HbA1c levels do not adequately capture risk-limiting utility as a triage tool in this cohort. Copyright © 2017 by the Endocrine Society

  12. High Frequency of Hb E-Saskatoon (HBB: c.67G > A) in Brazilians: A New Genetic Origin?

    Science.gov (United States)

    Wagner, Sandrine C; Lindenau, Juliana D; Castro, Simone M de; Santin, Ana Paula; Zaleski, Carina F; Azevedo, Laura A; Ribeiro Dos Santos, Ândrea K C; Dos Santos, Sidney E B; Hutz, Mara H

    2016-08-01

    Hb E-Saskatoon [β22(B4)Glu→Lys, HBB: c.67G > A] is a rare, nonpathological β-globin variant that was first described in a Canadian woman of Scottish and Dutch ancestry and has since then been detected in several populations. The aim of the present study was to identify the origin of Hb E-Saskatoon in Brazil using β-globin haplotypes and genetic ancestry in carriers of this hemoglobin (Hb) variant. Blood samples were investigated by isoelectric focusing (IEF) and high performance liquid chromatography (HPLC) using commercial kits. Hb E-Saskatoon was confirmed by amplification of the HBB gene, followed by sequence analysis. Haplotypes of the β-globin gene were determined by polymerase chain reaction (PCR), followed by digestion with specific restriction enzymes. Individual ancestry was estimated with 48 biallelic insertion/deletions using three 16-plex PCR amplifications. The IEF pattern was similar to Hbs C (HBB: c.19G > A) and Hb E (HBB: c.79G > A) [isoelectric point (pI): 7.59-7.65], and HPLC results showed an elution in the Hb S (HBB: c.20A > T) window [retention time (RT): 4.26-4.38]. DNA sequencing of the amplified β-globin gene showed a mutation at codon 22 (GAA>AAA) corresponding to Hb E-Saskatoon. A total of 11 cases of this variant were identified. In nine unrelated individuals, Hb E-Saskatoon was in linkage disequilibrium with haplotype 2 [+ - - - -]. All subjects showed a high degree of European contribution (mean = 0.85). Hb E-Saskatoon occurred on the β-globin gene of haplotype 2 in all Brazilian carriers. These findings suggest a different genetic origin for this Hb variant from that previously described.

  13. HbA1c Variability as an Independent Correlate of Nephropathy, but Not Retinopathy, in Patients With Type 2 Diabetes

    Science.gov (United States)

    Penno, Giuseppe; Solini, Anna; Bonora, Enzo; Fondelli, Cecilia; Orsi, Emanuela; Zerbini, Gianpaolo; Morano, Susanna; Cavalot, Franco; Lamacchia, Olga; Laviola, Luigi; Nicolucci, Antonio; Pugliese, Giuseppe

    2013-01-01

    OBJECTIVE To examine the association of hemoglobin (Hb) A1c variability with microvascular complications in the large cohort of subjects with type 2 diabetes from the Renal Insufficiency And Cardiovascular Events (RIACE) Italian Multicenter Study. RESEARCH DESIGN AND METHODS Serial (3–5) HbA1c values collected in a 2-year period before enrollment were available from 8,260 subjects from 9 centers (of 15,773 patients from 19 centers). HbA1c variability was measured as the intraindividual SD of 4.52 ± 0.76 values. Diabetic retinopathy (DR) was assessed by dilated funduscopy. Chronic kidney disease (CKD) was defined based on albuminuria, as measured by immunonephelometry or immunoturbidimetry, and estimated glomerular filtration rate (eGFR) was calculated from serum creatinine. RESULTS Median and interquartile range of average HbA1c (HbA1c-MEAN) and HbA1c-SD were 7.57% (6.86–8.38) and 0.46% (0.29–0.74), respectively. The highest prevalence of microalbuminuria, macroalbuminuria, reduced eGFR, albuminuric CKD phenotypes, and advanced DR was observed when both HbA1c parameters were above the median and the lowest when both were below the median. Logistic regression analyses showed that HbA1c-SD adds to HbA1c-MEAN as an independent correlate of microalbuminuria and stages 1–2 CKD and is an independent predictor of macroalbuminuria, reduced eGFR, and stages 3–5 albuminuric CKD, whereas HbA1c-MEAN is not. The opposite was found for DR, whereas neither HbA1c-MEAN nor HbA1c-SD affected nonalbuminuric CKD. CONCLUSIONS In patients with type 2 diabetes, HbA1c variability affects (albuminuric) CKD more than average HbA1c, whereas only the latter parameter affects DR, thus suggesting a variable effect of these measures on microvascular complications. PMID:23491522

  14. A fully liquid DTaP-IPV-HB-PRP-T hexavalent vaccine for primary and booster vaccination of healthy Turkish infants and toddlers

    Science.gov (United States)

    Ceyhan, Mehmet; Yıldırım, İnci; Tezer, Hasan; Devrim, İlker; Feroldi, Emmanuel

    2017-08-23

    Background/aim: Immunogenicity and safety of a primary series of a fully liquid, hexavalent DTaP-IPV-HB-PRP-T vaccine given at 2, 3, and 4 months of age compared to licensed comparators and a DTaP-IPV-HB-PRP-T booster at 15?18 months were evaluated. Materials and methods: This was a Phase III, randomized, open-label trial. Primary series (no hepatitis B [HB] at birth) of DTaP-IPV-HB-PRP-T (N = 155) (group 1) or licensed control vaccines (DTaP-IPV//PRP-T and standalone HB: N = 155) (group 2) and DTaP-IPV-HB-PRP-T booster were administered. Noninferiority was evaluated 1 month postprimary series for anti-HB seroprotection (SP). All other analyses were descriptive. Safety was assessed from parental reports. Results: Postprimary series noninferiority of anti-HB ≥ 10 mIU/mL was demonstrated for the DTaP-IPV-HB-PRP-T vaccine (94.0%) compared to the licensed control (96.1%). Postprimary series primary SP and seroconversion (SC) rates were high and similar for both groups. Antibody persistence (prebooster) was high for each antigen and similar between groups except for HB, which was lower for DTaP-IPV-HB-PRP-T than for standalone HB. For each antigen except HB, DTaP-IPV-HB-PRP-T booster responses were high and similar in each group. Safety was good for primary and booster series and similar between groups. Conclusion: The DTaP-IPV-HB-PRP-T vaccine is immunogenic and safe when administered in a challenging primary series schedule without HB vaccination at birth.

  15. Uso da bioinformática na diferenciação molecular da Entamoeba histolytica e Entamoeba díspar - DOI: 10.4025/actascihealthsci.v30i2.2375 Molecular discrimination of Entamoeba histolytica and Entamoeba dispar by bioinformatics resources - DOI: 10.4025/actascihealthsci.v30i2.2375

    Directory of Open Access Journals (Sweden)

    Débora Sommer

    2008-12-01

    Full Text Available Amebíase invasiva, causada por Entamoeba histolytica, é microscopicamente indistinguível da espécie não-patogênica Entamoeba dispar. Com auxílio de ferramentas de bioinformática, objetivou-se diferenciar Entamoeba histolytica e Entamoeba dispar por técnicas moleculares. A análise foi realizada a partir do banco de dados da National Center for Biotechnology Information; pela pesquisa de similaridade de sequências, elegeu-se o gene da cisteína sintase. Um par de primer foi desenhado (programa Web Primer e foi selecionada a enzima de restrição TaqI (programa Web Cutter. Após a atuação da enzima, o fragmento foi dividido em dois, um com 255 pb e outro com 554 pb, padrão característico da E. histolytica. Na ausência de corte, o fragmento apresentou o tamanho de 809 pb, referente à E. dispar.Under microscopic conditions, the invasive Entamoeba histolytica is indistinguishable from the non-pathogenic species Entamoeba dispar. In this way, the present study was carried out to determine a molecular strategy for discriminating both species by the mechanisms of bioinformatics. The gene cysteine synthetase was considered for such a purpose by using the resources of the National Center for Biotechnology Information data bank in the search for similarities in the gene sequence. In this way, a primer pair was designed by the Web Primer program and the restriction enzyme TaqI was selected by the Web Cutter software program. The DNA fragment had a size of 809 bp before cutting, which is consistent with E. dispar. The gene fragment was partitioned in a first fragment with 255 bp and a second one with 554 bp, which is similar to the genetic characteristics of E. histolytica.

  16. Epigenetic and molecular profiles of erythroid cells after hydroxyurea treatment in sickle cell anemia

    Science.gov (United States)

    Steward, Shirley; Howard, Thad A.; Mortier, Nicole; Smeltzer, Matthew; Wang, Yong-Dong; Ware, Russell E.

    2011-01-01

    Hydroxyurea has been shown to be efficacious for the treatment of sickle cell anemia (SCA), primarily through the induction of fetal hemoglobin (HbF). However, the exact mechanisms by which hydroxyurea can induce HbF remain incompletely defined, although direct transcriptional effects and altered cell cycle kinetics have been proposed. In this study, we investigated potential epigenetic and alternative molecular mechanisms of hydroxyurea-mediated HbF induction by examining methylation patterns within the Gγ-globin promoter and miRNA expression within primary CD71+ erythrocytes of patients with SCA, both at baseline before beginning hydroxyurea therapy and after reaching maximum tolerated dose (MTD). Using both cross-sectional analysis and paired-sample analysis, we found that the highly methylated Gγ-globin promoter was inversely correlated to baseline HbF levels, but only slightly altered by hydroxyurea treatment. Conversely, expression of several specific miRNAs was significantly increased after hydroxyurea treatment, and expression of miR-26b and miR-151-3p were both associated with HbF levels at MTD. The significant associations identified in these studies suggest that methylation may be important for regulation of baseline HbF, but not after hydroxyurea treatment, whereas changes in miRNA expression may be associated with hydroxyurea-mediated HbF induction. This study was registered at ClinicalTrials.gov (NCT00305175). PMID:21921042

  17. A randomized, double-blind, placebo-controlled, phase II clinical trial to investigate the efficacy and safety of oral DA-1229 in patients with type 2 diabetes mellitus who have inadequate glycaemic control with diet and exercise.

    Science.gov (United States)

    Jung, Chang Hee; Park, Cheol-Young; Ahn, Kyu-Joeng; Kim, Nan-Hee; Jang, Hak-Chul; Lee, Moon-Kyu; Park, Joong-Yeol; Chung, Choon-Hee; Min, Kyung-Wan; Sung, Yeon-Ah; Park, Jeong-Hyun; Kim, Sung Jin; Lee, Hyo Jung; Park, Sung-Woo

    2015-03-01

    DA-1229 is a novel, potent and selective dipeptidyl peptidase-4 (DPP-IV) inhibitor that is orally bioavailable. We aimed to evaluate the optimal dose, efficacy and safety of DA-1229, in Korean subjects with type 2 diabetes mellitus suboptimally controlled with diet and exercise. We enrolled 158 patients (mean age, 53 years and a mean BMI, 25.6 kg/m(2) ). The mean baseline fasting plasma glucose level, HbA1c and duration of diabetes were 8.28 mmol/L, 7.6% (60 mmol/mol) and 3.9 years, respectively. After 2 or 6 weeks of an exercise and diet program followed by 2 weeks of a placebo period, the subjects were randomized into one of four groups for a 12-week active treatment period: placebo, 2.5, 5 or 10 mg of DA-1229. All three doses of DA-1229 significantly reduced HbA1c from baseline compared to the placebo group (-0.09 in the placebo group vs. -0.56, -0.66 and -0.61% in 2.5, 5 and 10-mg groups, respectively) but without any significant differences between the doses. Insulin secretory function, as assessed by homeostasis model assessment β-cell, the insulinogenic index, 2-h oral glucose tolerance test (OGTT) C-peptide and post-OGTT C-peptide area under the curve (AUC)0-2h, significantly improved with DA-1229 treatment. The incidence of adverse events was similar between the treatment groups and DA-1229 did not affect body weight or induce hypoglycaemic events. DA-1229 monotherapy (5 mg for 12 weeks) improved HbA1c, fasting plasma glucose level, OGTT results and β-cell function. This drug was well tolerated in Korean subjects with type 2 diabetes mellitus. © 2014 The Authors. Diabetes/Metabolism Research and Reviews published by John Wiley & Sons, Ltd.

  18. Enhancing Effect of Hydroxyurea on Hb F in Sickle Cell Disease: Ten-Year Egyptian Experience.

    Science.gov (United States)

    Youssry, Ilham; Abdel-Salam, Amina; Ismail, Rania; Bou-Fakhredin, Rayan; Mohamed Samy, Rania; Ezz El-Deen, Fatma; Taher, Ali T

    Patients with sickle cell disease experience hemolytic anemia and vaso-occlusions that result in pain, organ injury, and premature mortality. Several prospective studies have verified the efficacy and tolerability of hydroxyurea (HU), and demonstrated its efficacy in reducing painful vaso-occlusive crises (VOCs) in addition to its ability to increase Hb F levels. We aimed to evaluate the long-term effects of HU therapy on Hb F and assess its long term efficacy and safety in sickle cell disease patients. A retrospective study on 60 sickle cell disease patients was conducted. We studied the laboratory changes, frequency of VOCs per year, frequency of hospital admisions per year and number of transfusions per year, both before and after HU therapy. The follow-up period was 4 to 120 months. Hb F levels after HU therapy positively correlated with the duration of HU therapy, baseline Hb F levels and baseline total hemoglobin (Hb) (r = 0.4, p = 0.04; r = 0.45, p = 0.001; r = 0.5, p = 0.019, respectively) and inversely correlated with baseline total leucocyte count (r = -0.33, p = 0.034). Hydroxyurea therapy was associated with an increase in the total Hb and mean corpuscular volume (MCV) (p = 0.009, p = 0.000; respectively) and with a decrease in total leucocyte count, platelet count and reticulocyte count (p = 0.00, p = 0.03, p = 0.02, respectively). Moreover, a significant reduction in the frequency of VOCs, transfusion frequency and hospital admissions per year after HU therapy was shown in the studied subjects. Hydroxyurea induced an increase in Hb F level, which was maintained over time and was associated with clinical efficacy and acceptable safety.

  19. Development of pro-inflammatory phenotype in monocytes after engulfing Hb-activated platelets in hemolytic disorders.

    Science.gov (United States)

    Singhal, Rashi; Chawla, Sheetal; Rathore, Deepak K; Bhasym, Angika; Annarapu, Gowtham K; Sharma, Vandana; Seth, Tulika; Guchhait, Prasenjit

    2017-02-01

    Monocytes and macrophage combat infections and maintain homeostatic balance by engulfing microbes and apoptotic cells, and releasing inflammatory cytokines. Studies have described that these cells develop anti-inflammatory properties upon recycling the free-hemoglobin (Hb) in hemolytic conditions. While investigating the phenotype of monocytes in two hemolytic disorders-paroxysmal nocturnal hemoglobinuria (PNH) and sickle cell disease (SCD), we observed a high number of pro-inflammatory (CD14 + CD16 hi ) monocytes in these patients. We further investigated in vitro the phenotype of these monocytes and found an estimated 55% of CD14 + cells were transformed into the CD14 + CD16 hi subset after engulfing Hb-activated platelets. The CD14 + CD16 hi monocytes, which were positive for both intracellular Hb and CD42b (platelet marker), secreted significant amounts of TNF-α and IL-1β, unlike monocytes treated with only free Hb, which secreted more IL-10. We have shown recently the presence of a high number of Hb-bound hyperactive platelets in patients with both diseases, and further investigated if the monocytes engulfed these activated platelets in vivo. As expected, we found 95% of CD14 + CD16 hi monocytes with both intracellular Hb and CD42b in both diseases, and they expressed high TNF-α. Furthermore our data showed that these monocytes whether from patients or developed in vitro after treatment with Hb-activated platelets, secreted significant amounts of tissue factor. Besides, these CD14 + CD16 hi monocytes displayed significantly decreased phagocytosis of E. coli. Our study therefore suggests that this alteration of monocyte phenotype may play a role in the increased propensity to pro-inflammatory/coagulant complications observed in these hemolytic disorders-PNH and SCD. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Comparison of the Current Diagnostic Criterion of HbA1c with Fasting and 2-Hour Plasma Glucose Concentration

    Science.gov (United States)

    Karnchanasorn, Rudruidee; Huang, Jean; Feng, Wei; Chuang, Lee-Ming

    2016-01-01

    To determine the effectiveness of hemoglobin A1c (HbA1c) ≥ 6.5% in diagnosing diabetes compared to fasting plasma glucose (FPG) ≥ 126 mg/dL and 2-hour plasma glucose (2hPG) ≥ 200 mg/dL in a previously undiagnosed diabetic cohort, we included 5,764 adult subjects without established diabetes for whom HbA1c, FPG, 2hPG, and BMI measurements were collected. Compared to the FPG criterion, the sensitivity of HbA1c ≥ 6.5% was only 43.3% (106 subjects). Compared to the 2hPG criterion, the sensitivity of HbA1c ≥ 6.5% was only 28.1% (110 subjects). Patients who were diabetic using 2hPG criterion but had HbA1c HbA1c ≥ 6.5%. The diagnostic agreement in the clinical setting revealed the current HbA1c ≥ 6.5% is less likely to detect diabetes than those defined by FPG and 2hPG. HbA1c ≥ 6.5% detects less than 50% of diabetic patients defined by FPG and less than 30% of diabetic patients defined by 2hPG. When the diagnosis of diabetes is in doubt by HbA1c, FPG and/or 2hPG should be obtained. PMID:27597979

  1. Impact of HbA1c Testing at Point of Care on Diabetes Management

    Science.gov (United States)

    Schnell, Oliver; Crocker, J. Benjamin; Weng, Jianping

    2016-01-01

    Diabetes is a highly prevalent disease also implicated in the development of several other serious complications like cardiovascular or renal disease. HbA1c testing is a vital step for effective diabetes management, however, given the low compliance to testing frequency and, commonly, a subsequent delay in the corresponding treatment modification, HbA1c at the point of care (POC) offers an opportunity for improvement of diabetes care. In this review, based on data from 1999 to 2016, we summarize the evidence supporting a further implementation of HbA1c testing at POC, discuss its limitations and propose recommendations for further development. PMID:27898388

  2. Structural and Functional Characterization of a New Double Variant Haemoglobin (HbG-Philadelphia/Duarte α(2)β(2)).

    Science.gov (United States)

    Fais, Antonella; Casu, Mariano; Ruggerone, Paolo; Ceccarelli, Matteo; Porcu, Simona; Era, Benedetta; Anedda, Roberto; Sollaino, Maria Carla; Galanello, Renzo; Corda, Marcella

    2011-01-01

    WE REPORT THE FIRST CASE OF COSEGREGATION OF TWO HAEMOGLOBINS (HBS): HbG-Philadelphia [α68(E17)Asn → Lys] and HbDuarte [β62(E6)Ala → Pro]. The proband is a young patient heterozygous also for β°-thalassaemia. We detected exclusively two haemoglobin variants: HbDuarte and HbG-Philadelphia/Duarte. Functional study of the new double variant HbG-Philadelphia/Duarte exhibited an increase in oxygen affinity, with a slight decrease of cooperativity and Bohr effect. This functional behaviour is attributed to β62Ala → Pro instead of α68Asn → Lys substitution. Indeed, HbG-Philadelphia isolated in our laboratory from blood cells donor carrier for this variant is not affected by any functional modification, whereas purified Hb Duarte showed functional properties very similar to the double variant. NMR and MD simulation studies confirmed that the presence of Pro instead of Ala at the β62 position produces displacement of the E helix and modifications of the tertiary structure. The substitution α68(E17)Asn → Lys does not cause significant structural and dynamical modifications of the protein. A possible structure-based rational of substitution effects is suggested.

  3. Molecular mechanisms of Porphyromonas gingivalis-host cell interaction on periodontal diseases

    Directory of Open Access Journals (Sweden)

    Masaaki Nakayama

    2017-11-01

    Full Text Available Porphyromonas gingivalis (P. gingivalis is a major oral pathogen and associated with periodontal diseases including periodontitis and alveolar bone loss. In this review, we indicate that two virulence factors, which are hemoglobin receptor protein (HbR and cysteine proteases “gingipains”, expressed by P. gingivalis have novel functions on the pathogenicity of P. gingivalis. P. gingivalis produces three types of gingipains and concomitantly several adhesin domains. Among the adhesin domains, hemoglobin receptor protein (HbR, also called HGP15, has the function of induction of interleukin-8 (IL-8 expression in human gingival epithelial cells, indicating the possibility that HbR is associated with P. gingivalis-induced periodontal inflammation. On bacteria-host cells contact, P. gingivalis induces cellular signaling alteration in host cells. Phosphatidylinositol 3-kinase (PI3K and Akt are well known to play a pivotal role in various cellular physiological functions including cell survival and glucose metabolism in mammalian cells. Recently, we demonstrated that gingipains attenuate the activity of PI3K and Akt, which might have a causal influence on periodontal diseases by chronic infection to the host cells from the speculation of molecular analysis. In this review, we discuss new molecular and biological characterization of the virulence factors from P. gingivalis.

  4. Investigation of local heterogeneity of hbO2 and hb in working dog heart in situ under isovolemic hemodilution and critical coronary stenosis

    Science.gov (United States)

    Krug, Alfons; Kessler, Manfred D.; Khuri, Raja; Lust, Robert; Chitwood, Randolph

    1996-12-01

    A tissue spectrophotometer (EMPHO II) working with 70 micrometer micro lightguide sensors enables recording of spectra in the visible wavelength range (500 - 630 nm). During an initial period arterial hypoxia and hyperoxia were induced on working dog heart by mechanical ventilation with oxygen fractions (fiO2) of 0.1 and 0.5. Under these conditions the effects of low and high fiO2 on oxygenation distribution of intracapillary hemoglobin were investigated. In the second part of the experiment the relation between systemic hematocrit, local hemoglobin concentration, local hemoglobin oxygenation and the oxygen regulation mechanism were studied in detail. In the final part of the experiment the effect of critical coronary stenosis on hb and hbO2 was measured. Critical stenosis was achieved by partial clamping of the left anterior coronary artery (LAD).

  5. Capsicum annuum homeobox 1 (CaHB1) is a nuclear factor that has roles in plant development, salt tolerance, and pathogen defense

    Energy Technology Data Exchange (ETDEWEB)

    Oh, Sang-Keun; Yoon, Joonseon [Department of Plant Science, College of Agriculture and Life Sciences, Seoul National University, Seou1 151-742 (Korea, Republic of); Choi, Gyung Ja [Screening Division, Korea Research Institute of Chemical Technology, Daejeon 305-600 (Korea, Republic of); Jang, Hyun A; Kwon, Suk-Yoon [Korea Research Institute of Bioscience and Biotechnology, Yusung, Daejeon 305-600 (Korea, Republic of); Choi, Doil, E-mail: doil@snu.ac.kr [Department of Plant Science, College of Agriculture and Life Sciences, Seoul National University, Seou1 151-742 (Korea, Republic of)

    2013-12-06

    Highlights: •The CaHB1 is a nuclear factor, belonging to HD-Zip proteins. •SA and ET, as signal molecules, modulate CaHB1-mediated responses. •Overexpression of CaHB1 in tomato resulted in a thicker cell wall. •CaHB1-transgenic tomato confers resistance to Phytophthora infestans. •CaHB1 enhanced tolerance to saline stress in tomato. -- Abstract: Homeodomain-leucine zipper (HD-Zip) family proteins are unique to plants, but little is known about their role in defense responses. CaHB1 is a nuclear factor in peppers, belonging to subfamily II of HD-Zip proteins. Here, we determined the role of CaHB1 in the defense response. CaHB1 expression was induced when pepper plants were challenged with Phytophthora capsici, a plant pathogen to which peppers are susceptible, or environmental stresses such as drought and salt stimuli. CaHB1 was also highly expressed in pepper leaves following application of SA, whereas ethephon and MeJA had a moderate effect. To further investigate the function of CaHB1 in plants, we performed gain-of-function study by overexpression of CaHB1 in tomato. CaHB1-transgenic tomatoes showed significant growth enhancement including increased leaf thickness and enlarged cell size (1.8-fold larger than control plants). Microscopic analysis revealed that leaves from CaHB1-transgenic plants had thicker cell walls and cuticle layers than those from controls. Moreover, CaHB1-transgenic plants displayed enhanced resistance against Phytophthora infestans and increased tolerance to salt stress. Additionally, RT-PCR analysis of CaHB1-transgenic tomatoes revealed constitutive up-regulation of multiple genes involved in plant defense and osmotic stress. Therefore, our findings suggest roles for CaHB1 in development, salt stress, and pathogen defense.

  6. Capsicum annuum homeobox 1 (CaHB1) is a nuclear factor that has roles in plant development, salt tolerance, and pathogen defense

    International Nuclear Information System (INIS)

    Oh, Sang-Keun; Yoon, Joonseon; Choi, Gyung Ja; Jang, Hyun A; Kwon, Suk-Yoon; Choi, Doil

    2013-01-01

    Highlights: •The CaHB1 is a nuclear factor, belonging to HD-Zip proteins. •SA and ET, as signal molecules, modulate CaHB1-mediated responses. •Overexpression of CaHB1 in tomato resulted in a thicker cell wall. •CaHB1-transgenic tomato confers resistance to Phytophthora infestans. •CaHB1 enhanced tolerance to saline stress in tomato. -- Abstract: Homeodomain-leucine zipper (HD-Zip) family proteins are unique to plants, but little is known about their role in defense responses. CaHB1 is a nuclear factor in peppers, belonging to subfamily II of HD-Zip proteins. Here, we determined the role of CaHB1 in the defense response. CaHB1 expression was induced when pepper plants were challenged with Phytophthora capsici, a plant pathogen to which peppers are susceptible, or environmental stresses such as drought and salt stimuli. CaHB1 was also highly expressed in pepper leaves following application of SA, whereas ethephon and MeJA had a moderate effect. To further investigate the function of CaHB1 in plants, we performed gain-of-function study by overexpression of CaHB1 in tomato. CaHB1-transgenic tomatoes showed significant growth enhancement including increased leaf thickness and enlarged cell size (1.8-fold larger than control plants). Microscopic analysis revealed that leaves from CaHB1-transgenic plants had thicker cell walls and cuticle layers than those from controls. Moreover, CaHB1-transgenic plants displayed enhanced resistance against Phytophthora infestans and increased tolerance to salt stress. Additionally, RT-PCR analysis of CaHB1-transgenic tomatoes revealed constitutive up-regulation of multiple genes involved in plant defense and osmotic stress. Therefore, our findings suggest roles for CaHB1 in development, salt stress, and pathogen defense

  7. C-Window Peaks on CE-HPLC are Extremely Rare in Northern India, and Only Infrequently Represent HbC.

    Science.gov (United States)

    Dass, Jasmita; Mittal, Suchi; Saraf, Amrita; Kotwal, Jyoti

    2018-01-01

    Hemoglobin C (HbC, HBB:c.19G > A) is a structural variant that has been reported rarely from India. This was a retrospective review of all high performance liquid chromatography (HPLCs) submitted over a 14 year period to a tertiary care center in North India with an aim of finding hemoglobins that elute in the C-window. Of the 32,364 HPLCs screened, 6 cases showed peaks in the C-window. Of these 6 cases, only two cases contained hemoglobin C. These was one case each of HbC/β thalassemia and compound heterozygosity for HbC and HbD. There were 4 cases which showed very similar red cell indices and chromatograms with multiple peaks eluting in D-window, C-window and an additional peak with a retention time of 4.74 min. These four cases were compound heterozygous for an α chain variant HbQ-India and a β-chain variant HbD.

  8. Serum Heparin-binding Epidermal Growth Factor-like Growth Factor (HB-EGF) as a Biomarker for Primary Ovarian Cancer.

    Science.gov (United States)

    Miyata, Kohei; Yotsumoto, Fusanori; Fukagawa, Satoshi; Kiyoshima, Chihiro; Ouk, Nam Sung; Urushiyama, Daichi; Ito, Tomohiro; Katsuda, Takahiro; Kurakazu, Masamitsu; Araki, Ryota; Sanui, Ayako; Miyahara, Daisuke; Murata, Masaharu; Shirota, Kyoko; Yagi, Hiroshi; Takono, Tadao; Kato, Kiyoko; Yaegashi, Nobuo; Akazawa, Kohei; Kuroki, Masahide; Yasunaga, Shin'ichiro; Miyamoto, Shingo

    2017-07-01

    Ovarian cancer is the most lethal malignancy among gynaecological cancers. Although many anticancer agents have been developed for the treatment of ovarian cancer, it continues to have an extremely poor prognosis. Heparin-binding epidermal growth factor-like grown factor (HB-EGF) has been reported to be a rational therapeutic target for ovarian cancer. Here, we evaluated the clinical significance of serum HB-EGF by examining the association between prognosis and serum HB-EGF levels in patients with primary ovarian cancer. We found that high serum HB-EGF concentrations were significantly associated with poor prognosis in a combined cohort of patients with all stages of ovarian cancer, as well as in a subset of patients with advanced disease. In addition, serum HB-EGF levels increased as the cancer advanced. These data suggest that serum HB-EGF may be a target for the design of novel therapies for ovarian cancer. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  9. Is high pressure liquid chromatography an effective screening tool for characterization of molecular defects in hemoglobinopathies?

    Directory of Open Access Journals (Sweden)

    Nikhil Moorchung

    2013-01-01

    Full Text Available Introduction: Hemoglobinopathies constitute entities that are generated by either abnormal hemoglobin or thalassemias. high pressure liquid chromatography (HPLC is one of the best methods for screening and detection of various hemoglobinopathies but it has intrinsic interpretive problems. The study was designed to evaluate the different mutations seen in cases of hemoglobinopathies and compare the same with screening tests. Materials and Methods: 68 patients of hemoglobinopathies were screened by HPLC. Mutation studies in the beta globin gene was performed using the polymerase chain reaction (PCR-based allele-specific Amplification Refractory Mutation System (ARMS. Molecular analysis for the sickle cell mutation was done by standard methods. Results: The IVS 1/5 mutation was the commonest mutation seen and it was seen in 26 (38.23% of the cases. This was followed by the IVS 1/1, codon 41/42, codon 8/9, del 22 mutation, codon 15 mutation and the -619 bp deletion. No mutation was seen in eight cases. There was a 100% concordance between the sickle cell trait as diagnosed by HPLC and genetic testing. Discussion and Conclusion: Our study underlies the importance of molecular testing in all cases of hemoglobinopathies. Although HPLC is a useful screening tool, molecular testing is very useful in accurately diagnosing the mutations. Molecular testing is especially applicable in cases with an abnormal hemoglobin (HbD, HbE and HbS because there may be a concomitant inheritance of a beta thalassemia mutation. Molecular testing is the gold standard when it comes to the diagnosis of hemoglobinopathies.

  10. Correlation of same-visit HbA1c test with laboratory-based measurements: A MetroNet study

    Directory of Open Access Journals (Sweden)

    West Patricia A

    2005-07-01

    Full Text Available Abstract Background Glycated hemoglobin (HbA1c results vary by analytical method. Use of same-visit HbA1c testing methodology holds the promise of more efficient patient care, and improved diabetes management. Our objective was to test the feasibility of introducing a same-visit HbA1c methodology into busy family practice centers (FPC and to calculate the correlation between the same-visit HbA1c test and the laboratory method that the clinical site was currently using for HbA1c testing. Methods Consecutive diabetic patients 18 years of age and older having blood samples drawn for routine laboratory analysis of HbA1c were asked to provide a capillary blood sample for same-visit testing with the BIO-RAD Micromat II. We compared the results of the same-visit test to three different laboratory methods (one FPC used two different laboratories. Results 147 paired samples were available for analysis (73 from one FPC; 74 from the other. The Pearson correlation of Micromat II and ion-exchange HPLC was 0.713 (p Conclusion For each of the laboratory methods, the correlation coefficient was lower than the 0.96 reported by the manufacturer. This might be due to variability introduced by the multiple users of the Micromat II machine. The mean HbA1c results were also consistently lower than those obtained from laboratory analysis. Additionally, the amount of dedicated time required to perform the assay may limit its usefulness in a busy clinical practice. Before introducing a same-visit HbA1c methodology, clinicians should compare the rapid results to their current method of analysis.

  11. Efficacy of acarbose and metformin in newly diagnosed type 2 diabetes patients stratified by HbA1c levels.

    Science.gov (United States)

    Zhang, Jin-Ping; Wang, Na; Xing, Xiao-Yan; Yang, Zhao-Jun; Wang, Xin; Yang, Wen-Ying

    2016-07-01

    The aim of the present study was to investigate whether the therapeutic efficacy of acarbose and metformin is correlated with baseline HbA1c levels in Chinese patients with newly diagnosed type 2 diabetes mellitus (T2DM). Data for 711 subjects were retrieved from the MARCH (Metformin and AcaRbose in Chinese as initial Hypoglycemic treatment) trial database and reviewed retrospectively. Patients were grouped according to baseline HbA1c levels (8%) and the results for these three groups were compared between acarbose and metformin treatments. Acarbose and metformin treatment significantly improved T2DM-associated parameters (weight, fasting plasma glucose [FPG], postprandial glucose [PPG], glucagon-like peptide-1 [GLP-1], HOMA-IR, and total cholesterol) across all HbA1c levels. Acarbose decreased PPG and HOMA-β significantly more than metformin, but only in subjects with lower baseline HbA1c (PPG in the HbA1c levels (P HbA1c groups (all P HbA1c levels, whereas metformin induced greater reductions in FPG. These results may help guide selection of initial therapy based on baseline HbA1c. © 2015 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.

  12. Heparin-Binding EGF-like Growth Factor (HB-EGF) Therapy for Intestinal Injury: Application and Future Prospects

    Science.gov (United States)

    Yang, Jixin; Su, Yanwei; Zhou, Yu; Besner, Gail E.

    2014-01-01

    Throughout the past 20 years, we have been investigating the potential therapeutic roles of heparin-binding EGF-like growth factor (HB-EGF), a member of the epidermal growth factor family, in various models of intestinal injury including necrotizing enterocolitis (NEC), intestinal ischemia/reperfusion (I/R) injury, and hemorrhagic shock and resuscitation (HS/R). Our studies have demonstrated that HB-EGF acts as an effective mitogen, a restitution-inducing reagent, a cellular trophic factor, an anti-apoptotic protein and a vasodilator, via its effects on various cell types in the intestine. In the current paper, we have reviewed the application and therapeutic effects of HB-EGF in three classic animal models of intestinal injury, with particular emphasis on its protection of the intestines from NEC. Additionally, we have summarized the protective functions of HB-EGF on various target cells in the intestine. Lastly, we have provided a brief discussion focusing on the future development of HB-EGF clinical applications for the treatment of various forms of intestinal injury including NEC. PMID:24345808

  13. Biochemical and molecular investigations on qualitative and quantitative Hb polymorphism in the river buffalo (Bubalus bubalis L. population reared in Southern Italy

    Directory of Open Access Journals (Sweden)

    Mario Iorio

    2004-01-01

    Full Text Available On 398 river buffalo samples, randomly collected in distinct breeding areas of the Campania region, high-resolution analytical systems were used to identify both qualitative and quantitative variations of the Hb phenotype. Polyacrylamide gel isoelectric focusing and HPLC were used to determine the ratio between HBA1 and HBA2 globin chains; restriction endonuclease analysis was performed to assess whether quantitative variations in Hb bands were related to an unusual number of a-globin genes. In the two buffalo subpopulations, allele frequencies of the alpha and beta globin systems were calculated, and F statistics (FIS, FIT and FST were estimated as parameters of genetic diversity. The results suggest that: i as shown by RFLP analysis, only a couple of associated a globin genes account for the quantitative variations recorded at the phenotypic level; ii as expected, in the a globin gene system (HBA, the frequency of haplotype B (HBA-B largely exceeded that of haplotype A (HBA-A (95.1% vs 4.9%; iii the frequency of the usual allele at the beta locus is 0.6, as opposed to 0.4 of the slow variant; iiii the most significant component of variation of the genetic system of hemoglobin is between individuals within the same location.

  14. Carbonyl Functionalized Single-Walled Carbon Nanotube-Hb Crosslinked Network: A Novel Platform for Studying Bio-Electrochemistry and Electrocatalysis of Hemoglobin.

    Science.gov (United States)

    Kafi, A K M; Yam, C C L; Azmi, N S; Yusoff, Mashitah M

    2018-04-01

    In this work, the direct electrochemistry of hemoglobin (Hb), which was immobilized on carbonyl functionalized single walled carbon nanotube (SWCNT) and deposited onto a gold (Au) electrode has been described. The synthesis of the network of crosslinked SWCNT/Hb was done with the help of crosslinking agent EDC (1-ethyl-3-(3-dimethylaminopropyl) carbodiimide). The UV-Vis and FTIR spectroscopy of SWCNT/Hb networks showed that Hb maintained its natural structure and kept good stability. In addition with this, scanning electron microscopy (SEM) illustrated that SWCNT/Hb networks had a featured layered structure and Hb being strongly liked with SWCNT surface. Cyclic voltammetry (CV) was used to study and to optimize the performance of the resulting modified electrode. The cyclic voltammetric (CV) responses of SWCNT/Hb networks in pH 7.0 exhibit prominent redox couple for the FeIII/II redox process with a midpoint potential of -0.46 V and -0.34, cathodic and anodic respectively. Furthermore, SWCNT/Hb networks are utilized for the detection of hydrogen peroxide (H2O2). Electrochemical measurements reveal that the resulting SWCNT/Hb electrodes display high electrocatalytic activity to H2O2 with high sensitivity, wide linear range, and low detection limit. Overall, the electrochemical results are due to excellent biocompatibility and excellent electron transport efficiency of CNT as well as high Hb loading and synergistic catalytic effect of the modified electrode toward H2O2.

  15. Plasma microRNA-451 as a novel hemolytic marker for β0-thalassemia/HbE disease

    Science.gov (United States)

    Leecharoenkiat, Kamonlak; Tanaka, Yuka; Harada, Yasuko; Chaichompoo, Porntip; Sarakul, Orawan; Abe, Yasunobu; Smith, Duncan Richard; Fucharoen, Suthat; Svasti, Saovaros; Umemura, Tsukuru

    2017-01-01

    In Southeast Asia, particularly in Thailand, β0-thalassemia/hemoglobin E (HbE) disease is a common hereditary hematological disease. It is associated with pathophysiological processes, such as the intramedullary destruction of immature erythroid cells and peripheral hemolysis of mature red blood cells. MicroRNA (miR) sequences, which are short non-coding RNA that regulate gene expression in a suppressive manner, serve a crucial role in human erythropoiesis. In the present study, the plasma levels of the erythroid-expressed miRNAs, miR-451 and miR-155, were analyzed in 23 patients with β0-thalassemia/HbE and 16 control subjects. Reverse transcription-quantitative polymerase chain reaction analysis revealed significantly higher levels of plasma miR-451 and miR-155 in β0-thalassemia/HbE patients when compared to the control subjects. Notably, among the β0-thalassemia/HbE patients, a significant increase in miR-451 levels was detected in severe cases when compared with mild cases. The levels of plasma miR-451 correlated with reticulocyte and platelet counts. The results suggest that increased plasma miR-451 levels may be associated with the degree of hemolysis and accelerated erythropoiesis in β0-thalassemia/HbE patients. In conclusion, miR-451 may represent a relevant biomarker for pathological erythropoiesis associated with β0-thalassemia/HbE. PMID:28447765

  16. Further studies on Hb Canebière [β12(G4)Asn→His], a low affinity hemoglobin variant

    DEFF Research Database (Denmark)

    Froelund, Ulf; Sandbakken, Erik; Szecsi, Pal Bela

    2010-01-01

    A case of Hb Canebière [ß102(G4)Asn¿His] was diagnosed in an otherwise healthy 21-year-old Danish woman. The clinical consequences were minor, since her only symptom consisted of transient cyanosis in lips and fingers when exposed to cold environments. Whole blood p50 was 59.9 mmHg. The Hb Canebi...... Canebière variant could not be separated from Hb A by high performance liquid chromatography (HPLC) and isoelectric focusing (IEF), and it was thus missed by routine hemoglobin (Hb) fractionation techniques....

  17. Further studies on Hb Canebière [β12(G4)Asn→His], a low affinity hemoglobin variant

    DEFF Research Database (Denmark)

    Froelund, Ulf; Sandbakken, Erik; Szecsi, Pal Bela

    2010-01-01

    A case of Hb Canebière [β102(G4)Asn→His] was diagnosed in an otherwise healthy 21-year-old Danish woman. The clinical consequences were minor, since her only symptom consisted of transient cyanosis in lips and fingers when exposed to cold environments. Whole blood p50 was 59.9 mmHg. The Hb...... Canebière variant could not be separated from Hb A by high performance liquid chromatography (HPLC) and isoelectric focusing (IEF), and it was thus missed by routine hemoglobin (Hb) fractionation techniques....

  18. MdHB1 down-regulation activates anthocyanin biosynthesis in the white-fleshed apple cultivar 'Granny Smith'.

    Science.gov (United States)

    Jiang, Yonghua; Liu, Cuihua; Yan, Dan; Wen, Xiaohong; Liu, Yanli; Wang, Haojie; Dai, Jieyu; Zhang, Yujie; Liu, Yanfei; Zhou, Bin; Ren, Xiaolin

    2017-02-01

    Coloration in apple (Malus×domestica) flesh is mainly caused by the accumulation of anthocyanin. Anthocyanin is biosynthesized through the flavonoid pathway and regulated by MYB, bHLH, and WD40 transcription factors (TFs). Here, we report that the HD-Zip I TF MdHB1 was also involved in the regulation of anthocyanin accumulation. MdHB1 silencing caused the accumulation of anthocyanin in 'Granny Smith' flesh, whereas its overexpression reduced the flesh content of anthocyanin in 'Ballerina' (red-fleshed apple). Moreover, flowers of transgenic tobacco (Nicotiana tabacum 'NC89') overexpressing MdHB1 showed a remarkable reduction in pigmentation. Transient promoter activation assays and yeast one-hybrid results indicated that MdHB1 indirectly inhibited expression of the anthocyanin biosynthetic genes encoding dihydroflavonol-4-reductase (DFR) and UDP-glucose:flavonoid 3-O-glycosyltransferase (UFGT). Yeast two-hybrid and bimolecular fluorescence complementation determined that MdHB1 acted as a homodimer and could interact with MYB, bHLH, and WD40 in the cytoplasm, consistent with its cytoplasmic localization by green fluorescent protein fluorescence observations. Together, these results suggest that MdHB1 constrains MdMYB10, MdbHLH3, and MdTTG1 to the cytoplasm, and then represses the transcription of MdDFR and MdUFGT indirectly. When MdHB1 is silenced, these TFs are released to activate the expression of MdDFR and MdUFGT and also anthocyanin biosynthesis, resulting in red flesh in 'Granny Smith'. © The Author 2017. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  19. Hb Belluno [β111(G13)Val→Gly;β133(H11)Val→Val (HBB: c.335T > G;402G > C)]: Incidental Detection of a New Clinically Silent β Chain Variant During Hb A1c Determination by High Performance Liquid Chromatography.

    Science.gov (United States)

    Pianezze, Graziano; Toniolo, Manuele; Taddei Masieri, Marina; Dolcini, Bernardetta; Ravani, Anna

    2016-06-01

    A previously unreported β chain variant, Hb Belluno [β111(G13)Val→Gly;β133(H11)Val→Val (HBB: c.335T > G;402G > C)], was incidentally discovered in a woman suffering from diabetes, during glycated hemoglobin (Hb A1c) assay. Its presence was suspected because of a small abnormal peak with a retention time just shorter than that of normal Hb A1c. Standard high performance liquid chromatography (HPLC), capillary zone electrophoresis (CZE) and agarose gel electrophoresis did not allow to separate the variant from Hb A. The reversed phase HPLC of globin chains showed the presence of a heterozygous β-globin variant amounting to approximately 43.5% of the total β chains. Later, this variant was found in five other members of the same family and DNA sequencing analysis confirmed a β-globin gene mutation. The variant is clinically silent in all patients and showed a slight instability with both heat and isopropanol tests. The other three mutations at this locus also affect stability. Hemoglobin (Hb) variants may invalidate the results of Hb A1c analysis and could result in mismanagement of diabetes. A comment alerting the requesting clinician to the presence of the Hb variant must be appended to the Hb A1c result. Additionally, many Hb variants can be chromatographically and/or electrophoretically silent. Therefore, when the clinician suspects a variant Hb, it is not sufficient to get a negative response from an HPLC screening test to rule it out. A dialogue with the pathologist is essential, involving exchange of information and sharing a diagnostic work-up including surveys to assess Hb stability and oxygen affinity, as much as DNA sequencing.

  20. [Hb Burgos (α1 CD64(E13)(Asp→Asn)): a new hemoglobin variant detected during follow-up of diabetic patients].

    Science.gov (United States)

    de la Fuente-Gonzalo, Félix; Martínez Nieto, Jorge; Torrejón, María José; Mayor, Luis Antonio; Velasco, Diego; González Fernández, Fernando Ataulfo; Ropero Gradilla, Paloma

    2015-01-06

    The glycated hemoglobin (HbA1c) test by high performance liquid chromatography is a useful tool for the follow-up of diabetes mellitus patients. Some structural hemoglobin (Hb) variants are known to cause interference in the analytical measurement of HbA1c. In this study, it has been characterized a new Hb variant in 4 patients during their regular control of HbA1c. Selective α1 gene sequencing showed a mutation GAC>AAC at codon 64 within exon 2. This produces a change of aspartic acid (Asp) by asparagine (Asn) that does not produce any functional alteration so the resultant molecule behaves as a silent hemoglobinopathy. The structural Hb variants can be detected during the analysis of HbA1c and may alter its values. Though rare, this occurrence signals the need to being aware when measuring HbA1c. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

  1. Performance of HbA1c as an early diagnostic indicator of type 1 diabetes in children and youth.

    Science.gov (United States)

    Vehik, Kendra; Cuthbertson, David; Boulware, David; Beam, Craig A; Rodriguez, Henry; Legault, Laurent; Hyytinen, Mila; Rewers, Marian J; Schatz, Desmond A; Krischer, Jeffrey P

    2012-09-01

    The aim of this study was to evaluate HbA(1c) as an alternative criterion for impaired glucose tolerance (IGT) or type 1 diabetes (T1D) in high-risk subjects TrialNet Natural History (TrialNet) studies and had an HbA(1c) within 90 days of an OGTT with a 2-h plasma glucose (2-hPG) measure were included. An OGTT of 140-199 mg/dL defined IGT, and an OGTT with 2-hPG ≥200 mg/dL or fasting plasma glucose ≥126 mg/dL defined diabetes. HbA(1c) ≥5.7% defined IGT, and HbA(1c) ≥ 6.5% defined diabetes. Receiver-operating characteristic curve analysis was used to assess diagnostic accuracy of HbA(1c) compared with OGTT. There were 587 subjects from DPT-1, 884 from TrialNet, 91 from TEDDY, and 420 from TRIGR. As an indicator for IGT, HbA(1c) sensitivity was very low across the studies (8-42%), and specificity was variable (64-95%). With HbA(1c) ≥6.5% threshold used for T1D diagnosis, the sensitivity was very low and specificity was high (sensitivity and specificity: DPT-1 24 and 98%, TrialNet 28 and 99%, TEDDY 34 and 98%, and TRIGR 33 and 99%, respectively). The positive predictive value of HbA(1c) ≥6.5% for the development of T1D was variable (50-94%) across the four studies. HbA(1c) ≥6.5% is a specific but not sensitive early indicator for T1D in high-risk subjects <21 years of age diagnosed by OGTT or asymptomatic hyperglycemia. Redefining the HbA(1c) threshold is recommended if used as an alternative criterion in diagnosing T1D.

  2. Identification, Functional Study, and Promoter Analysis of HbMFT1, a Homolog of MFT from Rubber Tree (Hevea brasiliensis

    Directory of Open Access Journals (Sweden)

    Zhenghong Bi

    2016-03-01

    Full Text Available A homolog of MOTHER OF FT AND TFL1 (MFT was isolated from Hevea brasiliensis and its biological function was investigated. Protein multiple sequence alignment and phylogenetic analysis revealed that HbMFT1 conserved critical amino acid residues to distinguish MFT, FLOWERING LOCUS T (FT and TERMINAL FLOWER1 (TFL1-like proteins and showed a closer genetic relationship to the MFT-like group. The accumulation of HbMFT1 was generally detected in various tissues except pericarps, with the highest expression in embryos and relatively higher expression in roots and stems of seedlings, flowering inflorescences, and male and female flowers. HbMFT1 putative promoter analysis showed that tissue-specific, environmental change responsive and hormone-signaling responsive elements were generally present. HbMFT1 was strongly induced under a short-day condition at 28 °C, with the highest expression after the onset of a day. Overexpression of HbMFT1 inhibited seed germination, seedling growth, and flowering in transgenic Arabidopsis. The qRT-PCR further confirmed that APETALA1 (AP1 and FRUITFULL (FUL were drastically down-regulated in 35S::HbMFT1 plants. A histochemical β-glucuronidase (GUS assay showed that HbMFT1::GUS activity was mainly detected in stamens and mature seeds coinciding with its original expression and notably induced in rosette leaves and seedlings of transgenic Arabidopsis by exogenous abscisic acid (ABA due to the presence of ABA cis-elements in HbMFT1 promoter. These results suggested that HbMFT1 was mainly involved in maintenance of seed maturation and stamen development, but negatively controlled germination, growth and development of seedlings and flowering. In addition, the HbMFT1 promoter can be utilized in controlling transgene expression in stamens and seeds of rubber tree or other plant species.

  3. Smoking: the influence of carboxyhemoglobin (HbCO) on tumor oxygenation and response to radiation

    International Nuclear Information System (INIS)

    Siemann, D.W.; Hill, R.P.; Bush, R.S.

    1978-01-01

    The effectiveness of localized x radiation on the transplantable KHT sarcoma was studied in nonanesthetized C3H mice possessing blood carboxyhemoglobin (HbCO) levels similar to those observed in heavy smokers. HbCO values of 10 percent were induced in tumor-bearing animals, either acutely just prior to irradiation or chronically during tumor growth and irradiation, by allowing the mice to breathe gas mixtures containing carbon monoxide (CO) in air. Tumors were irradiated either with single doses of 1500, 2000, or 2500 rad or with seven 500 rad fractions given at 24 hr intervals. Tumor cell survival was determined using an in vivo lung colony or an in vitro agar colony assay. The results with single doses of radiation indicate that under conditions of both acute and chronic exposure, the presence of 10 percent HbCO in the blood of the mice at the time of irradiation increases the survival of tumor cells in the hypoxic region of the survival curve by a factor of 2. During the fractionated irradiation, tumor cell survival in the presence of a 10 percent blood HbCO level (induced either acutely or chronically) was found to be significantly higher than that observed in air breathing mice. The results indicate that HbCO levels, such as are observed in heavy smokers, result in a larger fraction of hypoxic tumor cells. These findings suggest that heavy smoking prior to treatment may worsen the prognosis of patients undergoing radiotherapy

  4. Association between effort-reward imbalance and glycosylated hemoglobin (HbA1c) among Chinese workers: results from SHISO study.

    Science.gov (United States)

    Xu, Weixian; Hang, Juan; Gao, Wei; Zhao, Yiming; Li, Weihong; Wang, Xinyu; Li, Zhaoping; Guo, Lijun

    2012-02-01

    The studies focusing on effort-reward imbalance and diabetes mellitus (DM)/glycosylated hemoglobin (HbA1c) are rare. We sought to examine the association between job stress evaluated by effort-reward imbalance (ERI) model and HbA1c in a Chinese population. We analyzed 680 subjects (465 men and 215 women) without DM or impaired glucose tolerance from the stress and health in Shenzhen workers (SHISO) study. Job stress was evaluated by effort-reward imbalance (ERI) model. HbA1c was measured by an automatic analyzer by means of high-performance liquid chromatography. The association between job stress and HbA1c was explored by variance analysis, partial correlations and multiple linear regression analysis. For women, effort, and ERI were positively associated with HbA1c (r = 0.22, p = 0,003; r = 0.21, p = 0.006, respectively), in contrast, reward was negatively associated with HbA1c (r = -0.17, p = 0.021), after controlling age, BMI and physical exercise in the partial correlation analysis; the similar results were confirmed in the multiple linear regression. No significant correlations between job stress and HbA1c were found for men. Effort and ERI are positively associated with HbA1c, and reward is inversely related to HbA1c among Chinese women. The association is not accounted for by age, BMI, and physical exercise. More efforts should be made to improve the job stress status of Chinese working women for the purpose of DM prevention.

  5. Hb Matera (HBB: c.167 T > A): A Second Case Detected in a Pregnant Chinese Woman by the Capillary Electrophoresis Method.

    Science.gov (United States)

    Li, You-qiong; Ye, Li-Hua; Mo, Yun

    2016-01-01

    Hb Matera (HBB: c.167 T > A) is an unstable β-globin gene variant with an ATG > AAG substitution at codon 55. Its coelution with Hb A2 on high performance liquid chromatography (HPLC) makes it difficult to discriminate between Hb Matera and Hb E (HBB: c.79 G > A) that also coelutes with Hb A2 in this method. However, we found that capillary electrophoresis (CE) was able to detect Hb Matera and discriminate it from Hb E, based on the quantification of the peaks and on hematological parameters.

  6. Associations between gestational diabetes mellitus and elevated HbA1c early postpartum in a multi-ethnic population.

    Science.gov (United States)

    Waage, Christin; Jenum, Anne Karen; Mdala, Ibrahimu; Berg, Jens Petter; Richardsen, Kåre; Birkeland, Kåre

    2017-04-01

    To investigate the prevalence of elevated HbA 1c 14 weeks postpartum in different ethnic groups and in women with and without gestational diabetes mellitus (GDM) in the index pregnancy and to explore demographic and biological factors from early pregnancy associated with elevated HbA 1c (HbA 1c ≥5.7% (≥39mmol/mol)) postpartum. From a cohort study in Oslo, Norway, we included 570 pregnant women, examined in gestational week 15, 28, and 14 weeks postpartum. The association between elevated HbA 1c and demographic and biological factors were assessed by logistic regression analyses. The prevalence of elevated HbA 1c postpartum was 23% in the total population, 15% among Western Europeans and 28% among women with ethnic minority background (p<0.01). In ethnic minorities elevated HbA 1c was found in 39% of women with recent GDM diagnosed by the World Health Organization 2013 criteria and in 21% of women without GDM (p<0.01), compared to 22% and 13% in Western Europeans (p=0.11). We found independent associations between elevated HbA 1c and ethnic minority background (OR 2.0, 95% CI 1.27, 3.18), and GDM (OR 2.04, 95% CI 1.35, 3.10) (p<0.01). The prevalence of elevated HbA 1c postpartum was 23%, and significantly higher among women with ethnic minority background irrespective of GDM. Copyright © 2016 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.

  7. Effect of Sulfation and Molecular Weight on Anticoagulant Activity of Dextran.

    Science.gov (United States)

    Drozd, N N; Logvinova, Yu S; Torlopov, M A; Udoratina, E V

    2017-02-01

    Sulfation (to 2.8) of dextrans with molecular weight of 150 and 20 kDa was followed by the appearance of anticoagulant activity that increased with decreasing their molecular weight and did not depend on antithrombin, plasma inhibitor of serine proteases of the blood coagulation system. Antithrombin activity of dextran sulfate with a molecular weight of 20 kDa reached 12.6-15.3 U/mg. Dextran sulfates with molecular weights of 20 and 150 kDa did not potentiate ADP-induced human platelet aggregation.

  8. Identifying the independent effect of HbA1c variability on adverse health outcomes in patients with Type 2 diabetes.

    Science.gov (United States)

    Prentice, J C; Pizer, S D; Conlin, P R

    2016-12-01

    To characterize the relationship between HbA 1c variability and adverse health outcomes among US military veterans with Type 2 diabetes. This retrospective cohort study used Veterans Affairs and Medicare claims for veterans with Type 2 diabetes taking metformin who initiated a second diabetes medication (n = 50 861). The main exposure of interest was HbA 1c variability during a 3-year baseline period. HbA 1c variability, categorized into quartiles, was defined as standard deviation, coefficient of variation and adjusted standard deviation, which accounted for the number and mean number of days between HbA 1c tests. Cox proportional hazard models predicted mortality, hospitalization for ambulatory care-sensitive conditions, and myocardial infarction or stroke and were controlled for mean HbA 1c levels and the direction of change in HbA 1c levels during the baseline period. Over a mean 3.3 years of follow-up, all HbA 1c variability measures significantly predicted each outcome. Using the adjusted standard deviation measure for HbA 1c variability, the hazard ratios for the third and fourth quartile predicting mortality were 1.14 (95% CI 1.04, 1.25) and 1.42 (95% CI 1.28, 1.58), for myocardial infarction and stroke they were 1.25 (95% CI 1.10, 1.41) and 1.23 (95% CI 1.07, 1.42) and for ambulatory-care sensitive condition hospitalization they were 1.10 (95% CI 1.03, 1.18) and 1.11 (95% CI 1.03, 1.20). Higher baseline HbA 1c levels independently predicted the likelihood of each outcome. In veterans with Type 2 diabetes, greater HbA 1c variability was associated with an increased risk of adverse long-term outcomes, independently of HbA 1c levels and direction of change. Limiting HbA 1c fluctuations over time may reduce complications. © 2016 Diabetes UK.

  9. HbA1c values calculated from blood glucose levels using truncated Fourier series and implementation in standard SQL database language.

    Science.gov (United States)

    Temsch, W; Luger, A; Riedl, M

    2008-01-01

    This article presents a mathematical model to calculate HbA1c values based on self-measured blood glucose and past HbA1c levels, thereby enabling patients to monitor diabetes therapy between scheduled checkups. This method could help physicians to make treatment decisions if implemented in a system where glucose data are transferred to a remote server. The method, however, cannot replace HbA1c measurements; past HbA1c values are needed to gauge the method. The mathematical model of HbA1c formation was developed based on biochemical principles. Unlike an existing HbA1c formula, the new model respects the decreasing contribution of older glucose levels to current HbA1c values. About 12 standard SQL statements embedded in a php program were used to perform Fourier transform. Regression analysis was used to gauge results with previous HbA1c values. The method can be readily implemented in any SQL database. The predicted HbA1c values thus obtained were in accordance with measured values. They also matched the results of the HbA1c formula in the elevated range. By contrast, the formula was too "optimistic" in the range of better glycemic control. Individual analysis of two subjects improved the accuracy of values and reflected the bias introduced by different glucometers and individual measurement habits.

  10. Polar bear hemoglobin and human Hb A0: same 2,3-diphosphoglycerate binding site but asymmetry of the binding?

    Science.gov (United States)

    Pomponi, Massimo; Bertonati, Claudia; Patamia, Maria; Marta, Maurizio; Derocher, Andrew E; Lydersen, Christian; Kovacs, Kit M; Wiig, Oystein; Bårdgard, Astrid J

    2002-11-01

    Polar bear (Ursus maritimus) hemoglobin (Hb) shows a low response to 2,3-diphosphoglycerate (2,3-DPG), compared to human Hb A0, even though these proteins have the same 2,3-DPG-binding site. In addition, polar bear Hb shows a high response to chloride and an alkaline Bohr effect (deltalog P50/deltapH) that is significantly greater than that of human Hb A0. The difference in sequence Pro (Hb A0)-->Gly (polar bear Hb) at position A2 in the A helix seems to be critical for reduced binding of 2,3-DPG. Our results also show that the A2 position may influence not only the flexibility of the A helix, but that differences in flexibility of the first turn of the A helix may affect the unloading of oxygen for the intrinsic ligand affinities of the alpha and beta chains. However, preferential binding to either chain can only take place if there is appreciable asymmetric binding of the phosphoric effector. Regarding this point, 31P NMR data suggest a loss of symmetry of the 2,3-DPG-binding site in the deoxyHb-2,3-DPG complex.

  11. Effect of the systemic inflammatory response, as provoked by elective orthopaedic surgery, on HbA1c.

    Science.gov (United States)

    Chadburn, Andrew J; Garman, Elizabeth; Abbas, Raad; Modupe, Anu; Ford, Clare; Thomas, Osmond L; Chugh, Sanjiv; Deshpande, Shreeram; Gama, Rousseau

    2017-07-01

    Background In acutely ill patients with new onset hyperglycaemia, plasma glucose cannot reliably distinguish between stress hyperglycaemia and undiagnosed diabetes mellitus. We, therefore, investigated the diagnostic reliability of glycated haemoglobin (HbA1c) in acute illness by prospectively evaluating the effect of the systemic inflammatory response, as provoked by elective orthopaedic surgery, on HbA 1c . Methods HbA 1c and serum C-reactive protein concentrations were compared before and two days after elective knee or hip surgery in 30 patients without diabetes. C-reactive protein was used to assess the systemic inflammatory response. Results The mean (standard deviation) serum C-reactive protein increased following surgery (4.8 [7.5] vs. 179.7 [61.9] mg/L; P<0.0001). HbA 1c was similar before and after surgery (39.2 [5.4] vs. 38.1 [5.1] mmol/moL, respectively; P = 0.4363). Conclusions HbA 1c is unaffected within two days of a systemic inflammatory response as provoked by elective orthopaedic surgery. This suggests that HbA 1c may be able to differentiate newly presenting type 2 diabetes mellitus from stress hyperglycaemia in acutely ill patients with new onset hyperglycaemia.

  12. Alternate site testing for HbA1c using the Primus CLC330 GHb analyzer.

    Science.gov (United States)

    Phillipov, G; Charles, P; Beng, C; Phillips, P J

    1997-04-01

    To determine whether the Primus high-pressure liquid chromatography (HPLC) is suited to alternate site testing (AST) for HbA1c in a hospital diabetes outpatient clinic. Patients were attending the clinic for routine management of their diabetes. A number of diabetic patients with uremia (n = 11) were also investigated. HbA1c levels were measured in the outpatient setting by the Primus HPLC and in a more limited study the DCA-2000 instrument using the new 6-min assay cartridge. HbA1c measurements were also performed with Pierce affinity minicolumns and a Bio-Rad Variant HPLC. The Primus HPLC assay had low imprecision of 2.3, 1.6, and 1.0% for HbA1c levels of 4.7, 7.3, and 11.1%, respectively, and was not prone to interference by carbamylated hemoglobin as found for the ion-exchange Variant HPLC method. Method comparison studies showed that the bias and proportional error between the Pierce affinity minicolumn procedure (standardized with respect to an external quality control program) and the Primus HPLC (Y) was -0.4 and 1.2% respectively (n = 32). Similarly the bias and proportional error between the Primus and DCA-2000 methods was 0.7 and -2.5%. The Primus was shown to give falsely elevated HbA1c concentrations if the time between sequential injections was > 28 min. The Primus HPLC has a decided advantage over specialty AST instruments, like the DCA-2000, in not only meeting AST requirements but also allowing rapid automated batch processing of all laboratory HbA1c samples.

  13. Association between HbA1c and carotid atherosclerosis among elderly Koreans with normal fasting glucose.

    Directory of Open Access Journals (Sweden)

    Seung Won Lee

    Full Text Available We examined whether glycated haemoglobin (HbA1c is associated to carotid atherosclerosis in an elderly Korean population with normal fasting glucose.Using data from the Korean Urban Rural Elderly study, we conducted a cross-sectional analysis of 1,133 participants (335 men and 798 women with a mean age of 71.8 years. All participants had fasting blood glucose less than 100mg/dL (5.6 mmol/L and HbA1c level below 6.5% (48 mmol/mol. They were also free from a history of cardiovascular disease, known type 2 diabetes mellitus or use of anti-diabetes medications. Carotid atherosclerosis was assessed by intima-media thickness (IMT using ultrasonography. The association between HbA1c and carotid IMT was investigated using multivariable linear regression analysis.HbA1c levels were independently and positively associated with carotid IMT (β = 0.020, p = 0.045 after adjusting for sex, age, body mass index, systolic blood pressure, diastolic blood pressure, triglyceride, LDL cholesterol, smoking and alcohol intake. However, fasting insulin and glucose levels were not associated with carotid IMT.HbA1c levels were positively associated with carotid atherosclerosis, as assessed by carotid IMT, in an elderly population with normoglycemia. Our study suggested that higher HbA1c level is an effective and informative marker of carotid atherosclerosis in an elderly population.

  14. Effect of ethnicity on HbA1c levels in individuals without diabetes: Systematic review and meta-analysis

    Science.gov (United States)

    Freitas, Priscila Aparecida Correa; Gross, Jorge Luiz

    2017-01-01

    Aims/Hypothesis Disparities in HbA1c levels have been observed among ethnic groups. Most studies were performed in patients with diabetes mellitus (DM), which may interfere with results due to the high variability of glucose levels. We conducted a systematic review and meta-analysis to investigate the effect of ethnicity on HbA1c levels in individuals without DM. Methods This is a systematic review with meta-analysis. We searched MEDLINE and EMBASE up to September 2016. Studies published after 1996, performed in adults without DM, reporting HbA1c results measured by certified/standardized methods were included. A random effects model was used and the effect size was presented as weighted HbA1c mean difference (95% CI) between different ethnicities as compared to White ethnicity. Results Twelve studies met the inclusion criteria, totalling data from 49,238 individuals. There were significant differences between HbA1c levels in Blacks [0.26% (2.8 mmol/mol); 95% CI 0.18 to 0.33 (2.0 to 3.6), p HbA1c values are higher in Blacks, Asians, and Latinos when compared to White persons. Although small, these differences might have impact on the use of a sole HbA1c point to diagnose DM in all ethnic populations. PMID:28192447

  15. beta-Thalassemia present in cis to a new beta-chain structural variant, Hb Vicksburg [beta 75 (E19)Leu leads to 0].

    Science.gov (United States)

    Adams, J G; Steinberg, M H; Newman, M V; Morrison, W T; Benz, E J; Iyer, R

    1981-01-01

    Hemoglobin Vicksburg was discovered in a 6-year-old Black boy who had been anemic since infancy. Examination of his hemolysate revealed 87.5% Hb F, 2.4% Hb A2, and 7.6% Hb Vicksburg, which had the electrophoretic and chromatographic properties of Hb A. Structural analysis of Hb Vicksburg demonstrated a deletion of leucine at beta 75(E19), a new variant. Hb Vicksburg was neither unstable nor subject to posttranslational degradation. The alpha/non-alpha biosynthetic ratio was 2.6. Because the proband appeared to be a mixed heterozygote for Hb Vicksburg and beta 0-thalassemia, Hb Vicksburg should have comprised the major portion of the hemolysate. Thus, Hb Vicksburg was synthesized at a rate considerably lower than would be expected on the basis of gene dosage. There was no reason to suspect abnormal translation of beta Vicksburg mRNA; in individuals with Hb St. Antoine (beta 74 and beta 75 deleted), the abnormal hemoglobin comprised 25% of the hemolysate in the simple heterozygote yet was unstable. Deletion of beta 75, therefore, would not in itself appear to lead to diminished synthesis. There was a profound deficit of beta Vicksburg mRNA when measured by liquid hybridization analysis with beta cDNA. The most plausible explanation for the low output of Hb Vicksburg is that a mutation for beta +-thalassemia is present in cis to the structural mutation.

  16. Measurement of HbA1c in Gingival Crevicular Blood Using a High Pressure Liquid Chromatography Procedure

    Science.gov (United States)

    Pesce, Michael A.; Strauss, Shiela M.; Rosedale, Mary; Netterwald, Jane; Wang, Hangli

    2016-01-01

    Objectives To validate an ion exchange high-pressure liquid chromatography (HPLC) method for measuring glycated hemoglobin (HbA1c) in gingival crevicular blood (GCB) spotted on filter paper, for use in screening dental patients for diabetes. Methods We collected the GCB specimens for this study from the oral cavities of patients during dental visits, using rigorous strategies to obtain GCB that was as free of debris as possible. The analytical performance of the HPLC method was determined by measuring the precision, linearity, carryover, stability of HbA1c in GCB, and correlation of HbA1c results in GCB specimens with finger-stick blood (FSB) specimens spotted on filter paper. Results The coefficients of variation (CVs) for the inter- and intrarun precision of the method were less than 2.0%. Linearity ranged between 4.2% and 12.4%; carryover was less than 2.0%, and the stability of the specimen was 6 days at 4°C and as many as 14 days at −70°C. Linear regression analysis comparing the HbA1c results in GCB with FSB yielded a correlation coefficient of 0.993, a slope of 0.981, and an intercept of 0.13. The Bland-Altman plot showed no difference in the HbA1c results from the GCB and FSB specimens at normal, prediabetes, and diabetes HbA1c levels. Conclusion We validated an HPLC method for measuring HbA1c in GCB; this method can be used to screen dental patients for diabetes. PMID:26489673

  17. Molecular epidemiological survey of hemoglobinopathies in the Wuxi region of Jiangsu Province, eastern China.

    Science.gov (United States)

    Lin, Min; Han, Zhi-Jun; Wang, Qian; Zheng, Lei; Wang, Yan; Yang, Hui; Huang, Yue; Lin, Fen; Zhan, Xiao-Fen; Lin, Chun-Ping; Wu, Jiao-Ren; Luo, Zhao-Yun; Liu, Jing-Bo; Yan, Zhi-He; Zheng, Shu-Yan; Zheng, Jia-Kun; Lu, Min; Zhu, Juan-Juan; Xie, Long-Xu; Yang, Li-Ye

    2013-01-01

    In order to determine the prevalence and molecular characterization of hemoglobinopathies in the Wuxi region of Jiangsu Province in the People's Republic of China (PRC), a total of 10,297 healthy people selected from a regional hospital were screened. Hemoglobin (Hb) electrophoresis, complete blood cell (CBC) count, polymerase chain reaction (PCR), DNA sequencing, reverse dot-blot and multiplex ligation-dependent probe amplification (MLPA) were used to detect Hb variants, thalassemias and hereditary persistence of fetal Hb (HPFH). Two thousand and twenty-one adult subjects were screened for thalassemia, five cases were identified as α-thalassemia (α-thal) carriers including three cases of the -α(3.7) (rightward) deletion, one case of the - -(SEA) deletion and one case of β-thal [IVS-II-654 (C>T), (HBB: c.316-197C>T)]. The incidence of Hb variants, thalassemia and HPFH/δβ-thal were 0.136% (14/10,297), 0.25% (5/2021) and 0.0001% (1/10,297), respectively. Eight genotypes of Hb variants were found, including Hb E [β26(B8)Glu→Lys, GAG>AAG; HBB: c.79G>A], Hb J-Bangkok [β56(D7)Gly→Asp (GGC>GAC); HBB; c.170G>A], Hb G-Coushatta [β22(4)Glu→Ala (GAA>GCA); HBB: c.68A>C], Hb Queens [α34(B15)Leu→Arg (CTG>CGG) (α2 or α1); HBA2: c.104T>G (or HBA1)], Hb I [α16(A14)Lys→Glu, AAG>GAG (α1); HBA1: c.49A>G], Hb Beijing [α16(A14)Lys→Asn (AAG>AAC or AAT) (α2 or α1); HBA2: c.51G>C (or HBA1) or 51G>T (or HBA1)], Hb Ube-2 [α68(E17)Asn→Asp (AAC>GAC) (α2 or α1); HBA2: c.205A>G (or HBA1)] and Hb G-Taipei [β22(B4)Glu→Gly (GAA>GGA); HBB: c.68A>G]. A Sicilian δβ(0)-thal, identified for the first time in Asia, was also found in this survey.

  18. A novel base change leading to Hb Vanderbilt [β89(F5)Ser→Arg, AGT>AGA].

    Science.gov (United States)

    Goodyer, Matthew J; Elhassadi, Ezzat I; Percy, Melanie J; McMullin, Mary F

    2011-01-01

    We describe a high oxygen affinity hemoglobin (Hb) variant (Hb Vanderbilt) as a result of a heterozygous novel base change from T to A at codon 89 (AGT>AGA) leading to an amino acid change from serine to arginine.

  19. DNA studies are necessary for accurate patient diagnosis in compound heterozygosity for Hb Adana (HBA2:c.179>A) with deletional or nondeletional α-thalassaemia.

    Science.gov (United States)

    Tan, Jin Ai Mary Anne; Kho, Siew Leng; Ngim, Chin Fang; Chua, Kek Heng; Goh, Ai Sim; Yeoh, Seoh Leng; George, Elizabeth

    2016-06-08

    Haemoglobin (Hb) Adana (HBA2:c.179>A) interacts with deletional and nondeletional α-thalassaemia mutations to produce HbH disorders with varying clinical manifestations from asymptomatic to severe anaemia with significant hepatosplenomegaly. Hb Adana carriers are generally asymptomatic and haemoglobin subtyping is unable to detect this highly unstable α-haemoglobin variant. This study identified 13 patients with compound heterozygosity for Hb Adana with either the 3.7 kb gene deletion (-α(3.7)), Hb Constant Spring (HbCS) (HBA2:c.427T>C) or Hb Paksé (HBA2:429A>T). Multiplex Amplification Refractory Mutation System was used for the detection of five deletional and six nondeletional α-thalassaemia mutations. Duplex-PCR was used to confirm Hb Paksé and HbCS. Results showed 84.6% of the Hb Adana patients were Malays. Using DNA studies, compound heterozygosity for Hb Adana and HbCS (α(codon 59)α/α(CS)α) was confirmed in 11 patients. A novel point in this investigation was that DNA studies confirmed Hb Paksé for the first time in a Malaysian patient (α(codon 59)α/α(Paksé)α) after nine years of being misdiagnosis with Hb Adana and HbCS (α(codon 59)α/α(CS)α). Thus, the reliance on haematology studies and Hb subtyping to detect Hb variants is inadequate in countries where thalassaemia is prevalent and caused by a wide spectrum of mutations.

  20. Correlation of MMP-9, GA, HbA1c, and adipokines levels with DR

    Directory of Open Access Journals (Sweden)

    Cheng Qian

    2017-12-01

    Full Text Available AIM: To investigate the correlation of matrix metalloproteinase -9(MMP-9, glycated albumin(GA, glycosylated hemoglobin(HbA1cand adipokines(including visfatin, resistin and leptinwith diabetic retinopathy(DR. METHODS: From March 2015 to March 2017, 74 patients with DR were treated in our hospital, including 40 patients(80 eyeswith non proliferative diabetic retinopathy(NPDRand 34 patients(68 eyeswith proliferative diabetic retinopathy(PDR, and diabetes mellitus 40 patients(80 eyeswith non DR(NDRand 40 healthy volunteers(80 eyeswere selected as controls, the levels of MMP-9, GA, HbA1c, visfatin, resistin and leptin in each group were detected. RESULTS: PDR group visfatin was 4.41±0.82ng/mL, was significantly lower than the NPDR group, NDR group and control group(PPPPrs=0.523, 0.461 and 0.414, Prs=-0.433, Prs=0.401 and 0.460, PCONCLUSION: MMP-9, GA, HbA1c, and adipokines may play a role in the development and progression of DR, in which MMP-9 is associated with adipokines, both are not significantly related to the levels of GA and HbA1c.

  1. Structural characterization of hemoglobins from Monilifera and Frenulata tubeworms (Siboglinids): first discovery of giant hexagonal-bilayer hemoglobin in the former "Pogonophora" group.

    Science.gov (United States)

    Meunier, Cédric; Andersen, Ann C; Bruneaux, Matthieu; Le Guen, Dominique; Terrier, Peran; Leize-Wagner, Emmanuelle; Zal, Franck

    2010-01-01

    Siboglinids are symbiotic polychete annelids having hemoglobins as essential oxygen- and sulfide-carriers for their endosymbiotic bacteria. We analyzed the structure of the hemoglobins from two species of siboglinids: the monilifera Sclerolinum contortum and the frenulata Oligobrachia webbi (i.e. haakonmosbiensis) from Norwegian cold seeps. Measured by Multi-Angle Laser Light Scattering (MALLS), Sclerolinum shows a 3190+/-50 kDa hexagonal bilayer hemoglobin (HBL-Hb) and a 461+/-46 kDa ring-Hb, just as vestimentifera, whereas Oligobrachia has a 409+/-3.7 kDa ring-Hb only. Electrospray Ionization-Mass Spectrometry (ESI-MS) showed Sclerolinum HBL-Hb composed of seven monomeric globins (15-16 kDa), three disulfide-bonded globin heterodimers and three linkers. The heterodimers always contain globin-b (15814.4+/-1.5 Da). Sclerolinum ring-Hb is composed of globins and dimers with identical masses as its HBL-Hb, but lacks linkers. Oligobrachia ring-Hb has three globin monomers (14-15 kDa) only, with no disulfide-bonded dimers. Comparison of Sclerolinum hemoglobins between Storegga and Haakon Mosby Mud Volcano, using the normalized height of deconvoluted ESI-MS peaks, shows differences in globin monomers abundances that could reflect genetic differences or differential gene expression between distinct seep populations. The discovery of HBL-Hb in Sclerolinum is a new element supporting the hypothesis of monilifera being phylogenetically more closely related to vestimentifera, than to frenulata.

  2. Targeting hepatic heparin-binding EGF-like growth factor (HB-EGF) induces anti-hyperlipidemia leading to reduction of angiotensin II-induced aneurysm development.

    Science.gov (United States)

    Kim, Seonwook; Yang, Lihua; Kim, Seongu; Lee, Richard G; Graham, Mark J; Berliner, Judith A; Lusis, Aldons J; Cai, Lei; Temel, Ryan E; Rateri, Debra L; Lee, Sangderk

    2017-01-01

    The upregulated expression of heparin binding EGF-like growth factor (HB-EGF) in the vessel and circulation is associated with risk of cardiovascular disease. In this study, we tested the effects of HB-EGF targeting using HB-EGF-specific antisense oligonucleotide (ASO) on the development of aortic aneurysm in a mouse aneurysm model. Low-density lipoprotein receptor (LDLR) deficient mice (male, 16 weeks of age) were injected with control and HB-EGF ASOs for 10 weeks. To induce aneurysm, the mice were fed a high fat diet (22% fat, 0.2% cholesterol; w/w) at 5 week point of ASO administration and infused with angiotensin II (AngII, 1,000ng/kg/min) for the last 4 weeks of ASO administration. We confirmed that the HB-EGF ASO administration significantly downregulated HB-EGF expression in multiple tissues including the liver. Importantly, the HB-EGF ASO administration significantly suppressed development of aortic aneurysms including thoracic and abdominal types. Interestingly, the HB-EGF ASO administration induced a remarkable anti-hyperlipidemic effect by suppressing very low density lipoprotein (VLDL) level in the blood. Mechanistically, the HB-EGF targeting suppressed hepatic VLDL secretion rate without changing heparin-releasable plasma triglyceride (TG) hydrolytic activity or fecal neutral cholesterol excretion rate. This result suggested that the HB-EGF targeting induced protection against aneurysm development through anti-hyperlipidemic effects. Suppression of hepatic VLDL production process appears to be a key mechanism for the anti-hyperlipidemic effects by the HB-EGF targeting.

  3. Prevalence and phenotype of diabetes and prediabetes using fasting glucose vs HbA1c in a Caribbean population.

    Science.gov (United States)

    Unwin, Nigel; Howitt, Christina; Rose, Angela Mc; Samuels, T Alafia; Hennis, Anselm Jm; Hambleton, Ian R

    2017-12-01

    Both fasting plasma glucose (FPG) and HbA1c are recommended for the diagnosis of diabetes and prediabetes by the American Diabetes Association (ADA), and for diabetes by the World Health Organization. The ADA guidance is influential on clinical practice in many developing countries, including in the Caribbean and Latin America. We aimed to compare the prevalence and characteristics of individuals identified as having diabetes and prediabetes by FPG and HbA1c in a predominantly African ancestry Caribbean population. A representative population-based sample of 1234 adults (≥25 years of age) resident in Barbados was recruited. Standard methods with appropriate quality control were used to collect data on height, weight, blood pressure, fasting lipids and history of diagnosed diabetes, and to measure fasting glucose and HbA1c. Those with previously diagnosed diabetes (n = 192) were excluded from the analyses. Diabetes was defined as: FPG ≥7.0 mmol/L or HbA1c ≥6.5%; prediabetes as: FPG ≥5.6 to prediabetes was higher by HbA1c compared to FPG: 41.7% (37.9, 45.6) vs 15.0% (12.8, 17.5). Overall 558 individuals had prediabetes by either measure, but only 107 on both. HbA1c, but not FPG, was significantly higher in women than men; and FPG, but not HbA1c, was significantly associated with raised triglycerides and low HDL cholesterol. The agreement between FPG and HbA1c defined hyperglycaemia is poor. In addition, there are some differences in the phenotype of those identified, and HbA1c gives a much higher prevalence of prediabetes. The routine use of HbA1c for screening and diagnosis in this population would have major implications for clinical and public health policies and resources. Given the lack of robust evidence, particularly for prediabetes, on whether intervention in the individuals identified would improve outcomes, this approach to screening and diagnosis cannot be currently recommended for this population.

  4. [Detecting HB-1 Expression Level in Bone Marrow of Acute Leukemia Patients by Real-Time Fluorescence Quantitative RT-PCR].

    Science.gov (United States)

    Wang, Qing-Yun; Li, Yuan; Ji, Li; Liang, Ze-Yin; Liu, Wei; Ren, Han-Yun; Qiu, Zhi-Xiang

    2018-02-01

    To investigate the expression level of HB-1 gene in patients with acute lymphoblastic leukemia (ALL) and the significance of HB-1 gene in monitoring of minimal residual disease (MRD). The method of real-time fluorescence quantitative RT-PCR (Taqman probe) was established to detect the expression levels of HB-1 gene; then the sensitivity, specificity and repeatability of this assay were evaluated and verified. The HB-1 gene expression levels in bone marrow of 183 cases of ALL, 70 cases of acute myeloid leukemias (AML), 52 cases of non-malignant hematologic diseases and 24 healthy hematopoietic stem cell donors were detected. The correlation of HB-1 level with diagnosis and relapse was analyzed by detecting bone marrow samples of 33 B-ALL. The sensitivity of this assay reached the 10 -4 level. The coefficient of variation for inter-batch and inter-tube of HB-1 were 6.79% and 4.80%, respectively. It was found that HB-1 gene specifically expressed in acute B lymphoblastic leukemia. The median expression levels of HB-1 gene in newly diagnosed and relapsed B-ALL patients were statistically significantly higher than those in ALL in complete remission(CR), newly diagnosed T-ALL, newly diagnosed AML, non-malignant hematologic diseases, and healthy hematopoietic stem cell donors(33.0% vs 0.68%, 0.07%, 0.02%, 0.58% and 0, respectively) (P0.05). The expression level of HB-1 gene declined sharply when B-ALL patients reached complete remission (0-7.99%, with median level 0.68%), but increased when relapsed (7.69%, 8.08% and 484.0% in 3 relapsed samples), which was in accordance with results of flow cytometry. HB-1 gene specifically expressed in acute B lymphoblastic leukemia cells. The established real-time fluorescence quantitative RT-PCR assay shows good sensitivity, specificity and repeatability, thus, can be used as a biological marker in the clinical detection, monitoring MRD and predicting of early relapse for B-ALL patients.

  5. Glycated haemoglobin (HbA1c ) and fasting plasma glucose relationships in sea-level and high-altitude settings.

    Science.gov (United States)

    Bazo-Alvarez, J C; Quispe, R; Pillay, T D; Bernabé-Ortiz, A; Smeeth, L; Checkley, W; Gilman, R H; Málaga, G; Miranda, J J

    2017-06-01

    Higher haemoglobin levels and differences in glucose metabolism have been reported among high-altitude residents, which may influence the diagnostic performance of HbA 1c . This study explores the relationship between HbA 1c and fasting plasma glucose (FPG) in populations living at sea level and at an altitude of > 3000 m. Data from 3613 Peruvian adults without a known diagnosis of diabetes from sea-level and high-altitude settings were evaluated. Linear, quadratic and cubic regression models were performed adjusting for potential confounders. Receiver operating characteristic (ROC) curves were constructed and concordance between HbA 1c and FPG was assessed using a Kappa index. At sea level and high altitude, means were 13.5 and 16.7 g/dl (P > 0.05) for haemoglobin level; 41 and 40 mmol/mol (5.9% and 5.8%; P < 0.01) for HbA 1c ; and 5.8 and 5.1 mmol/l (105 and 91.3 mg/dl; P < 0.001) for FPG, respectively. The adjusted relationship between HbA 1c and FPG was quadratic at sea level and linear at high altitude. Adjusted models showed that, to predict an HbA 1c value of 48 mmol/mol (6.5%), the corresponding mean FPG values at sea level and high altitude were 6.6 and 14.8 mmol/l (120 and 266 mg/dl), respectively. An HbA 1c cut-off of 48 mmol/mol (6.5%) had a sensitivity for high FPG of 87.3% (95% confidence interval (95% CI) 76.5 to 94.4) at sea level and 40.9% (95% CI 20.7 to 63.6) at high altitude. The relationship between HbA 1c and FPG is less clear at high altitude than at sea level. Caution is warranted when using HbA 1c to diagnose diabetes mellitus in this setting. © 2017 The Authors. Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK.

  6. Fermi LAT and WMAP observations of the supernova remnant HB 21

    Energy Technology Data Exchange (ETDEWEB)

    Pivato, G. [Dipartimento di Fisica e Astronomia " G. Galilei," Università di Padova, I-35131 Padova (Italy); Hewitt, J. W. [CRESST, University of Maryland, Baltimore County, Baltimore, MD 21250 (United States); Tibaldo, L. [W. W. Hansen Experimental Physics Laboratory, Kavli Institute for Particle Astrophysics and Cosmology, Department of Physics and SLAC National Accelerator Laboratory, Stanford University, Stanford, CA 94305 (United States); Acero, F.; Brandt, T. J. [NASA Goddard Space Flight Center, Greenbelt, MD 20771 (United States); Ballet, J. [Laboratoire AIM, CEA-IRFU/CNRS/Université Paris Diderot, Service d' Astrophysique, CEA Saclay, F-91191 Gif sur Yvette (France); De Palma, F.; Giordano, F. [Dipartimento di Fisica " M. Merlin" dell' Università e del Politecnico di Bari, I-70126 Bari (Italy); Janssen, G. H. [University of Manchester, Manchester, M13 9PL (United Kingdom); Jóhannesson, G. [Science Institute, University of Iceland, IS-107 Reykjavik (Iceland); Smith, D. A., E-mail: giovanna.pivato@pd.infn.it, E-mail: john.w.hewitt@nasa.gov, E-mail: ltibaldo@slac.stanford.edu [Centre d' Études Nucléaires de Bordeaux Gradignan, IN2P3/CNRS, Université Bordeaux 1, BP120, F-33175 Gradignan Cedex (France)

    2013-12-20

    We present the analysis of Fermi Large Area Telescope γ-ray observations of HB 21 (G89.0+4.7). We detect significant γ-ray emission associated with the remnant: the flux >100 MeV is 9.4 ± 0.8 (stat) ± 1.6 (syst) × 10{sup –11} erg cm{sup –2} s{sup –1}. HB 21 is well modeled by a uniform disk centered at l = 88.°75 ± 0.°04, b = +4.°65 ± 0.°06 with a radius of 1.°19 ± 0.°06. The γ-ray spectrum shows clear evidence of curvature, suggesting a cutoff or break in the underlying particle population at an energy of a few GeV. We complement γ-ray observations with the analysis of the WMAP 7 yr data from 23 to 93 GHz, achieving the first detection of HB 21 at these frequencies. In combination with archival radio data, the radio spectrum shows a spectral break, which helps to constrain the relativistic electron spectrum, and, in turn, parameters of simple non-thermal radiation models. In one-zone models multiwavelength data favor the origin of γ rays from nucleon-nucleon collisions. A single population of electrons cannot produce both γ rays through bremsstrahlung and radio emission through synchrotron radiation. A predominantly inverse-Compton origin of the γ-ray emission is disfavored because it requires lower interstellar densities than are inferred for HB 21. In the hadronic-dominated scenarios, accelerated nuclei contribute a total energy of ∼3 × 10{sup 49} erg, while, in a two-zone bremsstrahlung-dominated scenario, the total energy in accelerated particles is ∼1 × 10{sup 49} erg.

  7. Spinal Hb9::Cre-derived excitatory interneurons contribute to rhythm generation in the mouse

    DEFF Research Database (Denmark)

    Caldeira, Vanessa; Dougherty, Kimberly J.; Borgius, Lotta

    2017-01-01

    Rhythm generating neurons are thought to be ipsilaterally-projecting excitatory neurons in the thoracolumbar mammalian spinal cord. Recently, a subset of Shox2 interneurons (Shox2 non-V2a INs) was found to fulfill these criteria and make up a fraction of the rhythm-generating population. Here we...... than in cords from controls. Collectively, our findings indicate that excitatory Hb9::Cre-derived INs constitute a distinct population of neurons that participates in the rhythm generating kernel for spinal locomotion....... use Hb9::Cre mice to genetically manipulate Hb9::Cre-derived excitatory interneurons (INs) in order to determine the role of these INs in rhythm generation. We demonstrate that this line captures a consistent population of spinal INs which is mixed with respect to neurotransmitter phenotype...

  8. Exploring the ϒ (4 S ,5 S ,6 S )→hb(1 P )η hidden-bottom hadronic transitions

    Science.gov (United States)

    Zhang, Yawei; Li, Gang

    2018-01-01

    Recently, the Belle Collaboration has reported the measurement of the spin-flipping transition ϒ (4 S )→hb(1 P )η with an unexpectedly large branching ratio: B (ϒ (4 S )→hb(1 P )η )=(2.18 ±0.11 ±0.18 )×10-3 . Such a large branching fraction contradicts with the anticipated suppression for the spin flip. In this work, we examine the effects induced by intermediate bottomed meson loops and point out that these effects are significantly important. Using the effective Lagrangian approach (ELA), we find the experimental data on ϒ (4 S )→hb(1 P )η can be accommodated with the reasonable inputs. We then explore the decays ϒ (5 S ,6 S )→hb(1 P )η and find that these two channels also have sizable branching fractions. We also calculate these processes in the framework of nonrelativistic effective field theory (NREFT). For the decays ϒ (4 S )→hb(1 P )η , the NREFT results are at the same order of magnitude but smaller than the ELA results by a factor of 2 to 5. For the decays ϒ (5 S ,6 S )→hb(1 P )η , the NREFT results are smaller than the ELA results by approximately 1 order of magnitude. We suggest a future experiment Belle-II to search for the ϒ (5 S ,6 S )→hb(1 P )η decays, which will be helpful for understanding the transition mechanism.

  9. Changes in HbA1c and Weight Following Transition to Continuous Subcutaneous Insulin Infusion Therapy in Adults With Type 1 Diabetes.

    Science.gov (United States)

    Mehta, Sanjeev N; Andersen, Henrik Ullits; Abrahamson, Martin J; Wolpert, Howard A; Hommel, Eva E; McMullen, William; Ridderstråle, Martin

    2017-01-01

    Historically, intensive insulin therapy for type 1 diabetes (T1D) has improved glycemic control at the risk of adverse weight gain. The impact of continuous subcutaneous insulin infusion therapy (CSII) on weight in the current era remains unknown. We assessed changes in hemoglobin A1c (HbA1c) and weight in adults with T1D transitioning to CSII at 2 diabetes centers in Denmark and the United States. Patients with T1D, aged ≥18 years, managed with multiple daily injections (MDI) who transitioned to CSII between 2002 and 2013 were identified using electronic health record data from the Steno Diabetes Center (n = 600) and Joslin Diabetes Center (n = 658). Changes in HbA1c and weight after 1 year was assessed overall and by baseline HbA1c cut points. Multivariate regression assessed correlates of HbA1c reduction. In adults with T1D transitioning to CSII, clinically significant HbA1c reductions were found in patients with baseline HbA1c 8.0-8.9% (Steno, -0.7%; Joslin, -0.4%) and baseline HbA1c ≥9.0% (Steno, -1.1%; Joslin, -0.9%) ( P HbA1c ≥9% at Steno (1.1 ± 0.3 kg, P HbA1c reduction was associated with higher HbA1c, older age, female sex at Steno ( R 2 = .28, P HbA1c at Joslin ( R 2 = .19, P HbA1c without a negative impact on weight 1 year after transitioning from MDI to CSII.

  10. Discovery of recombining plasma from the faintest GeV supernova remnant HB 21 and a possible scenario for cosmic rays escaping from supernova remnant shocks

    Science.gov (United States)

    Suzuki, Hiromasa; Bamba, Aya; Nakazawa, Kazuhiro; Furuta, Yoshihiro; Sawada, Makoto; Yamazaki, Ryo; Koyama, Katsuji

    2018-06-01

    We present an X-ray study of the GeV gamma-ray supernova remnant (SNR) HB 21 with Suzaku. HB 21 is interacting with molecular clouds, and is the faintest in the GeV band among known GeV SNRs. We discovered strong radiative recombination continua of Si and S from the center of the remnant, which provide direct evidence of a recombining plasma (RP). The total emission can be explained with the RP and ionizing plasma components. The electron temperature and recombination timescale of the RP component were estimated as 0.17 (0.15-0.18) keV and 3.2 (2.0-4.8) × 1011 s cm-3, respectively. The estimated age of the RP (˜170 kyr) is the longest among known recombining GeV SNRs, because of a very low density of electrons (˜0.05 cm-3). We have examined the dependencies of GeV spectral indices on each of RP ages and SNR diameters for nine recombining GeV SNRs. Both showed possible positive correlations, indicating that both the parameters can be good indicators of properties of accelerated protons, for instance the degree of escape from SNR shocks. A possible scenario for a process of proton escape is introduced: interaction with molecular clouds makes weaker magnetic turbulence and cosmic-ray protons escape, simultaneously cooling down the thermal electrons and generating an RP.

  11. Structure of the 30 kDa HIV-1 RNA Dimerization Signal by a Hybrid Cryo-EM, NMR, and Molecular Dynamics Approach.

    Science.gov (United States)

    Zhang, Kaiming; Keane, Sarah C; Su, Zhaoming; Irobalieva, Rossitza N; Chen, Muyuan; Van, Verna; Sciandra, Carly A; Marchant, Jan; Heng, Xiao; Schmid, Michael F; Case, David A; Ludtke, Steven J; Summers, Michael F; Chiu, Wah

    2018-03-06

    Cryoelectron microscopy (cryo-EM) and nuclear magnetic resonance (NMR) spectroscopy are routinely used to determine structures of macromolecules with molecular weights over 65 and under 25 kDa, respectively. We combined these techniques to study a 30 kDa HIV-1 dimer initiation site RNA ([DIS] 2 ; 47 nt/strand). A 9 Å cryo-EM map clearly shows major groove features of the double helix and a right-handed superhelical twist. Simulated cryo-EM maps generated from time-averaged molecular dynamics trajectories (10 ns) exhibited levels of detail similar to those in the experimental maps, suggesting internal structural flexibility limits the cryo-EM resolution. Simultaneous inclusion of the cryo-EM map and 2 H-edited NMR-derived distance restraints during structure refinement generates a structure consistent with both datasets and supporting a flipped-out base within a conserved purine-rich bulge. Our findings demonstrate the power of combining global and local structural information from these techniques for structure determination of modest-sized RNAs. Copyright © 2018 Elsevier Ltd. All rights reserved.

  12. Comparison of 1,5-anhydroglucitol, HbA1c, and fructosamine for detection of diabetes mellitus.

    Science.gov (United States)

    Yamanouchi, T; Akanuma, Y; Toyota, T; Kuzuya, T; Kawai, T; Kawazu, S; Yoshioka, S; Kanazawa, Y; Ohta, M; Baba, S

    1991-01-01

    To evaluate the use of serum 1,5-anhydroglucitol (AG) levels in screening for diabetes mellitus, we compared the sensitivity and specificity of HbA1c, fructosamine (FA), and AG in 1620 randomly selected subjects in 11 institutions throughout Japan. Most individuals were receiving diet and/or drug therapy for diabetes. Subjects were separated into four groups based on World Health Organization criteria: nondiabetic control subjects, subjects with impaired glucose tolerance (IGT), patients with diabetes, and patients with other disorders without IGT. The overlap of AG values between each group was less than that of HbA1c or FA values. AG levels were significantly correlated with fasting plasma glucose (r = -0.627), HbA1c (r = -0.629), and FA (r = -0.590) levels. If we took 14 micrograms/ml as the normal lower limit, AG level was highly specific (93.1%), and a decreased AG level indicated diabetes mellitus (84.2% sensitivity). According to the selectivity index (sensitivity value times specificity value), AG determinations were superior to both HbA1c and FA measurements for diabetes screening. When combinations of these tests were used, only AG and HbA1c together were slightly better than AG alone. Thus, together with other advantages of AG, e.g., its wide variance with relatively fair glycemic control and the negligible influence of the sampling conditions, AG level has more potential than HbA1c or FA level as a screening criterion for diabetes.

  13. HbA1c Measured in Stored Erythrocytes Is Positively Linearly Associated with Mortality in Individuals with Diabetes Mellitus

    Science.gov (United States)

    Sluik, Diewertje; Boeing, Heiner; Montonen, Jukka; Kaaks, Rudolf; Lukanova, Annekatrin; Sandbaek, Annelli; Overvad, Kim; Arriola, Larraitz; Ardanaz, Eva; Saieva, Calogero; Grioni, Sara; Tumino, Rosario; Sacerdote, Carlotta; Mattiello, Amalia; Spijkerman, Annemieke M. W.; van der A, Daphne L.; Beulens, Joline W. J.; van Dieren, Susan; Nilsson, Peter M.; Groop, Leif C.; Franks, Paul W.; Rolandsson, Olov; Bueno-de-Mesquita, Bas; Nöthlings, Ute

    2012-01-01

    Introduction Observational studies have shown that glycated haemoglobin (HbA1c) is related to mortality, but the shape of the association is less clear. Furthermore, disease duration and medication may modify this association. This observational study explored the association between HbA1c measured in stored erythrocytes and mortality. Secondly, it was assessed whether disease duration and medication use influenced the estimates or were independently associated with mortality. Methods Within the European Prospective Investigation into Cancer and Nutrition a cohort was analysed of 4,345 individuals with a confirmed diagnosis of diabetes at enrolment. HbA1c was measured in blood samples stored up to 19 years. Multivariable Cox proportional hazard regression models for all-cause mortality investigated HbA1c in quartiles as well as per 1% increment, diabetes medication in seven categories of insulin and oral hypoglycaemic agents, and disease duration in quartiles. Results After a median follow-up of 9.3 years, 460 participants died. Higher HbA1c was associated with higher mortality: Hazard Ratio for 1%-increase was 1.11 (95% CI 1.06, 1.17). This association was linear (P-nonlinearity =0.15) and persistent across categories of medication use, disease duration, and co-morbidities. Compared with metformin, other medication types were not associated with mortality. Longer disease duration was associated with mortality, but not after adjustment for HbA1c and medication. Conclusion This prospective study showed that persons with lower HbA1c had better survival than those with higher HbA1c. The association was linear and independent of disease duration, type of medication use, and presence of co-morbidities. Any improvement of HbA1c appears to be associated with reduced mortality risk. PMID:22719972

  14. Entsymaattisen Abbott Architect c8000 HbA1c -menetelmän validointi

    OpenAIRE

    Karjalainen, Laura

    2013-01-01

    Opinnäytetyö suoritettiin THL:n Tautiriskiyksikön analyyttisen biokemian laboratoriossa (TLAB). Työssä validoitiin uusi entsymaattinen Abbott Architect c8000 HbA1c -menetelmä, jota käytetään diabetekseen liittyvissä tutkimuksissa. Validoinnilla haluttiin varmistaa uuden mittaustekniikaltaan erilaisen menetelmän toimivuus. Menetelmävertailussa komparatiivisena menetelmänä oli laboratoriossa rutiinikäytössä ollut Abbottin immunoturbidimetrinen HbA1c-menetelmä. Uusi entsymaattinen menetelmä peru...

  15. Capillary crystallization and molecular-replacement solution of haemoglobin II from the clam Lucina pectinata

    International Nuclear Information System (INIS)

    Gavira, José A.; Jesus, Walleska de; Camara-Artigas, Ana; López-Garriga, Juan; García-Ruiz, Juan M.

    2006-01-01

    The haemoglobin II from the clam L. pectinata has been crystallized using counter-diffusion in single capillary in the presence of agarose to improve crystal quality. Initial phases have been obtained by molecular replacement. Haemoglobin II is one of three haemoglobins present in the cytoplasm of the Lucina pectinata mollusc that inhabits the Caribbean coast. Using HBII purified from its natural source, crystallization screening was performed using the counter-diffusion method with capillaries of 0.2 mm inner diameter. Crystals of HbII suitable for data collection and structure determination were grown in the presence of agarose at 0.1%(w/v) in order to improve their quality. The crystals belong to the tetragonal space group P4 2 2 1 2, with unit-cell parameters a = b = 73.92, c = 152.35 Å, and diffracted X-rays to a resolution of better than 2.0 Å. The asymmetric unit is a homodimer with a corresponding Matthews coefficient (V M ) of 3.15 Å 3 Da −1 and a solvent content of 61% by volume

  16. Risk of progression to diabetes from prediabetes defined by HbA1c or fasting plasma glucose criteria in Koreans.

    Science.gov (United States)

    Kim, Chul-Hee; Kim, Hong-Kyu; Kim, Eun-Hee; Bae, Sung-Jin; Choe, Jaewon; Park, Joong-Yeol

    2016-08-01

    To examine the abilities of HbA1c and fasting plasma glucose (FPG) criteria predicting 5-year progression rate to diabetes in Korean adults with prediabetes. Participants included 17,971 Koreans (aged 20-79years) who underwent routine medical check-ups at a mean interval of 5.2years (3.1-6.7years). Prediabetes was defined as FPG 5.6-6.9mmol/l or HbA1c 5.7-6.4% (39-46mmol/mol). Incident diabetes was defined as FPG⩾7.0mmol/l, HbA1c⩾6.5% (48mmol/mol), or initiation of antidiabetic medications. At baseline, the prevalence of prediabetes was 30.6% (n=5495) by FPG and 20.4% (n=3664) by HbA1c criteria. The 5-year progression rate to diabetes was significantly higher in prediabetes identified by HbA1c than by FPG tests (14.7% vs. 10.4%, Pprediabetes by only one test, those by HbA1c alone had a higher risk of progression to diabetes than those diagnosed by FPG alone (6.0% vs. 3.9%, Pprediabetes identified by HbA1c (OR 9.91, 8.24-11.9) than by FPG (OR 7.29, 5.97-8.89) (P=0.026). Although fewer individuals with prediabetes were identified by HbA1c than by FPG criteria, the ability to predict progression to diabetes was stronger for HbA1c than for FPG in Koreans. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  17. Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is increased in osteoarthritis and regulates chondrocyte catabolic and anabolic activities

    Science.gov (United States)

    Long, D.L.; Ulici, V.; Chubinskaya, S.; Loeser, R.F.

    2015-01-01

    Objective We determined if the epidermal growth factor receptor ligand HB-EGF is produced in cartilage and if it regulates chondrocyte anabolic or catabolic activity. Methods HB-EGF expression was measured by quantitative PCR using RNA isolated from mouse knee joint tissues and from normal and OA human chondrocytes. Immunohistochemistry was performed on normal and OA human cartilage and meniscus sections. Cultured chondrocytes were treated with fibronectin fragments (FN-f) as a catabolic stimulus and osteogenic protein 1 (OP-1) as an anabolic stimulus. Effects of HB-EGF on cell signaling were analyzed by immunoblotting of selected signaling proteins. MMP-13 was measured in conditioned media, proteoglycan synthesis was measured by sulfate incorporation, and matrix gene expression by quantitative PCR. Results HB-EGF expression was increased in 12-month old mice at 8 weeks after surgery to induce OA and increased amounts of HB-EGF were noted in human articular cartilage from OA knees. FN-f stimulated chondrocyte HB-EGF expression and HB-EGF stimulated chondrocyte MMP-13 production. However, HB-EGF was not required for FN-f stimulation of MMP-13 production. HB-EGF activated the ERK and p38 MAP kinases and stimulated phosphorylation of Smad1 at an inhibitory serine site which was associated with inhibition of OP-1 mediated proteoglycan synthesis and reduced aggrecan (ACAN) but not COL2A1 expression. Conclusion HB-EGF is a new factor identified in OA cartilage that promotes chondrocyte catabolic activity while inhibiting anabolic activity suggesting it could contribute to the catabolic-anabolic imbalance seen in OA cartilage. PMID:25937027

  18. Values of HbCO in 1000 inhabitants of Milan non exposed to occupational absorption of CO

    Energy Technology Data Exchange (ETDEWEB)

    Grisler, R.; Gobbi, A.; Giavardi, C.; Caimmi, G.; Soverini, R.; Botta, A.

    1975-01-01

    Carboxyhemoglobin levels for 1000 non-occupationally exposed inhabitants of Milan were determined. The study group consisted of smokers and non-smokers; among the former, only individuals refraining from smoking for at least 10 hr were tested. The upper limit of the normal range for HbCO values among non-smokers was 2.85%, while among heavy smokers it was 4.59%. Heavy smokers also showed higher HbCO levels than did moderate smokers. Elevated HbCO values were also observed among residents living in carbon monoxide-polluted urban areas as compared with those living in unpolluted rural areas.

  19. Canagliflozin provides greater attainment of both HbA1c and body weight reduction versus sitagliptin in patients with type 2 diabetes.

    Science.gov (United States)

    Schernthaner, Guntram; Lavalle-González, Fernando J; Davidson, Jaime A; Jodon, Holly; Vijapurkar, Ujjwala; Qiu, Rong; Canovatchel, William

    2016-11-01

    To evaluate the proportion of patients with type 2 diabetes mellitus (T2DM) achieving reductions in both glycated hemoglobin (HbA1c) and body weight with canagliflozin, a sodium glucose co-transporter 2 inhibitor, versus sitagliptin over 52 weeks. Data were pooled from two, randomized, Phase 3 studies of canagliflozin 100 and 300 mg versus sitagliptin 100 mg as add-on to metformin, and canagliflozin 300 mg versus sitagliptin 100 mg as add-on to metformin plus sulfonylurea (N = 1856). The composite end points of change from baseline in both HbA1c HbA1c HbA1c and body weight over 52 weeks versus sitagliptin. A greater proportion of patients had both HbA1c and body weight reductions with canagliflozin 100 and 300 mg versus sitagliptin 100 mg (67.7%, 72.6%, and 44.1%, respectively). Among patients with HbA1c and body weight reductions, more patients achieved the composite end point of HbA1c HbA1c and body weight, and more patients with HbA1c and body weight reductions achieved HbA1c <7.0% and body weight reduction ≥5% with canagliflozin versus sitagliptin over 52 weeks. www.ClinicalTrials.gov identifiers are NCT01106677; NCT01137812.

  20. Glycated hemoglobin HbA1c, waist circumference, and waist-to-height ratio in overweight and obese adolescents

    Directory of Open Access Journals (Sweden)

    Elysa Nur Safrida

    2017-04-01

    Full Text Available Background Central obesity has been associated with a high risk of insulin resistance. Waist circumference and waist-to-height ratio are anthropometric indices for determining central obesity and have been associated with increased blood pressure, cholesterol, and insulin levels. In adults, fat distribution around the waist is a valid predictor of glycated hemoglobin (HbA1clevels, and is currently recommended by experts as a diagnostic tool for diabetes. Central obesity measurement has advantages over fasting blood glucose and oral glucose tolerance tests, as it is simple and inexpensive to perform. Objective To assess for correlations between HbA1c level and waist circumference as well as waist-to-height ratio and to assess factors potentially associated with HbA1c levels in overweight and obese adolescents. Methods This cross-sectional study was done in four junior high schools in Yogyakarta, which were obtained by cluster sampling. Overweight and obese students who were generally healthy were included in the study. Subjects underwent waist circumference and waist-to-height ratio measurements, as well as blood tests for HbA1clevels. Results Sixty-seven children participated in the study, with 48 girls (71.6% and 19 boys (28.4%. Waist circumference and HbA1c levels were not significantly associated (r=0.178; P=0.15. However, waist-to-height ratio and HbA1c levels had a weak positive correlation (r=0.21; P=0.04. Linear regression analysis revealed that waist-to-height ratio had a significant association with HbA1c level (P=0.02, but age, sex, and nutritional status did not. Conclusion Waist-to-height ratio is correlated with HbA1c levels in overweight and obese adolescents.

  1. Can HbA1c be Used to Screen for Glucose Abnormalities Among Adults with Severe Mental Illness?

    Science.gov (United States)

    Romain, A J; Letendre, E; Akrass, Z; Avignon, A; Karelis, A D; Sultan, A; Abdel-Baki, A

    2017-04-01

    Aim: Prediabetes and type 2 diabetes are highly prevalent among individuals with serious mental illness and increased by antipsychotic medication. Although widely recommended, many obstacles prevent these patients from obtaining a proper screening for dysglycemia. Currently, glycated hemoglobin (HbA1c), fasting glucose, and 2-hour glucose levels from the oral glucose tolerance test are used for screening prediabetes and type 2 diabetes. The objective of this study was to investigate if HbA1c could be used as the only screening test among individuals with serious mental illness. Methods: Cross sectional study comparing the sensitivity of HbA1c, fasting glucose, and 2-h oral glucose tolerance test to detect dysglycemias in serious mental illness participants referred for metabolic complications. Results: A total of 84 participants (43 female; aged: 38.5±12.8 years; BMI: 35.0±6.8 kg/m²) was included. Regarding prediabetes, 44, 44 and 76% were identified by HbA1c, fasting glucose, and 2 h- oral glucose tolerance test respectively and for type 2 diabetes, 60, 53 and 66% were identified by HbA1c, fasting glucose and 2 h-oral glucose tolerance test. The overlap between the 3 markers was low (8% of participants for prediabetes and 26% for Type 2 diabetes). Sensitivity of HbA1c were moderate (range 40-62.5%), while its specificity was excellent (92-93%). Conclusion: The present study indicates a low agreement between HbA1c, fasting glucose and 2-h oral glucose tolerance test. It appears that these markers do not identify the same participants. Thus, HbA1c may not be used alone to detect all glucose abnormalities among individuals with serious mental illness. © Georg Thieme Verlag KG Stuttgart · New York.

  2. The Haber Bosch-harmful algal bloom (HB-HAB) link

    NARCIS (Netherlands)

    Glibert, P.M.; Maranger, R.; Sobota, D.J.; Bouwman, Lex|info:eu-repo/dai/nl/090428048

    2014-01-01

    Large-scale commercialization of the Haber–Bosch (HB) process is resulting in intensification of nitrogen (N) fertilizer use worldwide. Globally N fertilizer use is far outpacing that of phosphorus (P) fertilizer. Much of the increase in N fertilizers is also now in the form of urea, a reduced form

  3. CLD (chronic liver diseases)-HbA1C as a suitable indicator for estimation of mean plasma glucose in patients with chronic liver diseases.

    Science.gov (United States)

    Koga, Masafumi; Kasayama, Soji; Kanehara, Hideo; Bando, Yukihiro

    2008-08-01

    In patients with chronic liver diseases (CLD), turnover of erythrocytes is increased whereas that of serum albumin is decreased. Thus, glycated hemoglobin (HbA(1C)) and glycated albumin (GA) cannot be used as adequate indicators for chronic plasma glucose control in diabetic patients with CLD. In this investigation, we have proposed CLD-HbA(1C), a novel long-term glycemic control marker by using measured HbA(1C) and GA. We studied 82 patients with CLD in whom glycemic control was regarded as to be stable. Daily plasma glucose profiles were monitored and estimated levels of HbA(1C) were calculated on the conversion formula established by Rohlfing et al. [C.L. Rohlfing, J.D. England, H.M. Wiedmeyer, A. Tennill, R.R. Little, D.E. Goldstein, Defining the relationship between plasma glucose and HbA1c, Diabetes Care 25 (2002) 275-278]. Cholinesterase (ChE) as an indicator for hepatic function was determined at the same time when HbA(1C) and GA levels were measured. CLD-HbA(1C) was defined as the average of measured HbA(1C) and GA/3, based upon the results that among healthy individuals, GA levels were roughly estimated at approximately threefold higher than HbA(1C) levels. While measured HbA(1C) levels in patients with CLD were generally lower than estimated HbA(1C) levels, GA/3 values were generally higher than estimated HbA(1C) levels. Such discrepancies lineally increased in accordance with a decrease in ChE levels. On the other hand, CLD-HbA(1C) levels were highly correlated with estimated HbA(1C) levels (R=0.883), while no significant correlation between CLD-HbA(1C) and ChE was noted. In conclusion, CLD-HbA(1C) has been found a superior chronic glycemic control marker than HbA(1C) or GA in diabetic patients with chronic liver diseases.

  4. The 1-hour post-load glucose level is more effective than HbA1c for screening dysglycemia.

    Science.gov (United States)

    Jagannathan, Ram; Sevick, Mary Ann; Fink, Dorothy; Dankner, Rachel; Chetrit, Angela; Roth, Jesse; Buysschaert, Martin; Bergman, Michael

    2016-08-01

    To assess the performance of HbA1c and the 1-h plasma glucose (PG ≥ 155 mg/dl; 8.6 mmol/l) in identifying dysglycemia based on the oral glucose tolerance test (OGTT) from a real-world clinical care setting. This was a diagnostic test accuracy study. For this analysis, we tested the HbA1c diagnostic criteria advocated by the American Diabetes Association (ADA 5.7-6.4 %) and International Expert Committee (IEC 6.0-6.4 %) against conventional OGTT criteria. We also tested the utility of 1-h PG ≥ mg/dl; 8.6 mmol/l. Prediabetes was defined according to ADA-OGTT guidelines. Spearman correlation tests were used to determine the relationships between HbA1c, 1-h PG with fasting, 2-h PG and indices of insulin sensitivity and β-cell function. The levels of agreement between diagnostic methods were ascertained using Cohen's kappa coefficient (Κ). Receiver operating characteristic (ROC) curve was used to analyze the performance of the HbA1c and 1-h PG test in identifying prediabetes considering OGTT as reference diagnostic criteria. The diagnostic properties of different HbA1c thresholds were contrasted by determining sensitivity, specificity and likelihood ratios (LR). Of the 212 high-risk individuals, 70 (33 %) were identified with prediabetes, and 1-h PG showed a stronger association with 2-h PG, insulin sensitivity index, and β-cell function than HbA1c (P HbA1c criteria 0.1[0.03-0.16] and IEC criteria (0.17[0.04-0.30]). The ROC (AUC[95 % CI]) for HbA1c and 1-h PG were 0.65[0.57-0.73] and 0.79[0.72-0.85], respectively. Importantly, 1-h PG ≥ 155 mg/dl (8.6 mmol/l) showed good sensitivity (74.3 % [62.4-84.0]) and specificity 69.7 % [61.5-77.1]) with a LR of 2.45. The ability of 1-h PG to discriminate prediabetes was better than that of HbA1c (∆AUC: -0.14; Z value: 2.5683; P = 0.01022). In a real-world clinical practice setting, the 1-h PG ≥ 155 mg/dl (8.6 mmol/l) is superior for detecting high-risk individuals compared with HbA1c

  5. Possible discrepancy of HbA1c values and its assessment among patients with chronic renal failure, hemodialysis and other diseases.

    Science.gov (United States)

    Inoue, Kaori; Goto, Atsushi; Kishimoto, Miyako; Tsujimoto, Tetsuro; Yamamoto-Honda, Ritsuko; Noto, Hiroshi; Kajio, Hiroshi; Terauchi, Yasuo; Noda, Mitsuhiko

    2015-12-01

    Glycated hemoglobin (HbA1c) and glycated albumin (GA) are frequently used as glycemic control markers. However, these markers are influenced by alterations in hemoglobin and albumin metabolism. Thus, conditions such as anemia, chronic renal failure, hypersplenism, chronic liver diseases, hyperthyroidism, hypoalbuminemia, and pregnancy need to be considered when interpreting HbA1c or GA values. Using data from patients with normal albumin and hemoglobin metabolism, we previously established a linear regression equation describing the GA value versus the HbA1c value to calculate an extrapolated HbA1c (eHbA1c) value for the accurate evaluation of glycemic control. In this study, we investigated the difference between the measured HbA1c and the eHbA1c values for patients with various conditions. Data sets for a total of 2461 occasions were obtained from 731 patients whose HbA1c and GA values were simultaneously measured. We excluded patients with missing data or changeable HbA1c levels, and patients who had received transfusions or steroids within the previous 3 months. Finally, we included 44 patients with chronic renal failure (CRF), 10 patients who were undergoing hemodialysis (HD), 7 patients with hematological malignancies and a hemoglobin level of less than 10 g/dL (HM), and 12 patients with chronic liver diseases (CLD). In all the groups, the eHbA1c values were significantly higher than the measured HbA1c values. The median difference was 0.75 % (95 % CI 0.40-1.10 %, P for the difference is <0.001) in the CRF group, 0.80 % (95 % CI 0.30-1.65 %, P for the difference is 0.041) in the HD group, 0.90 % (95 % CI 0.90-1.30 %, P for the difference is 0.028) in the HM group, and 0.85 % (95 % CI 0.40-1.50 %, P for the difference is 0.009) in the CLD group. We found that the measured HbA1c values were lower than the eHbA1c values in each of the groups.

  6. Solids loading evaluation for HB-line scrap recovery filters

    International Nuclear Information System (INIS)

    Crowder, M.L.

    2000-01-01

    The HB-Line Scrap Recovery facility uses wire screen filters to remove solids from plutonium-containing solutions transferred from the slab tank dissolvers. At times, the accumulation of solids is large enough to cause blinding (i.e., pluggage) of the filters. If the solids contain undissolved plutonium, significant accumulation of fissile material could impact operations. To address this potential issue, experiments were performed to define the minimum solids required to completely blind a filter. The solids loading experiments were performed by arranging 25- and 10-microm HB-Line filters in series to simulate the equipment in the scrap recovery process. Separate tests were performed using coarse and fine glass frit and cerium oxide powder suspended in 35 wt% sodium nitrate solution using a small turbine mixer. The solution and solids were transferred from a reservoir through the filter housings by vacuum. In each case, the 25-microm filter blinded first and was full of wet cake. After drying and accounting for the sodium nitrate in the filter cake, the following results were obtained. The results of the solids loading tests demonstrated that at least 800 g of solids accumulated in the filter housing before flow stopped. The actual amount of collected material was dependent upon the physical properties of the solids such as density and particle size. The mass of solids collected by the blinded 25-microm filter increased when successively finer solids were used in the experiments. Based on these results, one should anticipate that filters in the HB-Line Scrap Recovery Facility have the potential to collect similar quantities of material before transfer of solution from the dissolvers is severely impacted

  7. Dilution Ratios for HB Line Phase I Eductor System

    International Nuclear Information System (INIS)

    Steimke, J.L.

    2002-01-01

    HB Line Phase I product transfer includes an eductor which transfers liquid from Product Hold Tank (PHT) RT-33 or RT-34 to Tank 11.1. The eductor also dilutes the liquid from the PHT with eductant. Dilution must be reliably controlled because of criticality concerns with H Canyon Tanks. The eductor system, which contains a 1 inch Model 264 Schutte and Koerting eductor, was previously modeled [1] in 1998 and dilution ratios were calculated for different flow restrictors, eductant pressures and densities for the eductant and the contents of the PHT. The previous calculation was performed using spreadsheet software no longer supported at SRS. For the previous work dilution ratio was defined as the volume of eductant consumed divided by volume of PHT contents transferred. Since 1998 HB Line Engineering has changed the definition of dilution ratio to the total volume of liquid, eductant consumed plus the volume of PHT liquid transferred, divided by the volume of PHT liquid transferred. The 1998 base case calculation was for a restrictor diameter of 0.334 inches, an eductant supply pressure of 15 psig, full PHT, an eductant specific gravity of 1.385 and a PHT density of 1.015. The base case dilution ratio calculated in 1998 using the current definition was 3.52. After accounting for uncertainty the minimum dilution ratio decreased to 3.23. In 2001 HB Line Engineering requested that the calculation be repeated for a manganous nitrate solution eductant and also a process water eductant. The other conditions were the same as for the 1998 calculation. The objective of this report is to document the calculations and the results

  8. Hb Agenogi [β90(F6)Glu→Lys (GAG>AAG) HBB: c.271G>A)] in a Pregnant Thai Woman.

    Science.gov (United States)

    Panyasai, Sitthichai; Thongsuk, Pollawat; Pornprasert, Sakorn

    2016-01-01

    Hb Agenogi [β90(F6)Glu→Lys (GAG>AAG) HBB: c.271G>A)] is a very rare β-globin chain variant. We report for the first time this hemoglobinopathy in a pregnant 20-year-old Thai woman. She was seen by an obstetrician at her 14th week of gestation. She was pale and had an inflammatory lesion of her lower left leg. The hemoglobin (Hb) analysis by high performance liquid chromatography (HPLC) and low pressure liquid chromatography (LPLC) showed a peak of abnormal Hb at the C window. On capillary electrophoresis (CE), the abnormal Hb peak was observed at electrophoretic zone 4 that corresponded to the Hb E (HBB: c.79G>A) peak. Direct DNA sequencing revealed a GAG>AAG mutation at codon 90 of the β-globin gene. Thus, even though Hb Agenogi is very rare, it can be found in Thai people. The knowledge and understanding of this hemoglobinopathy will be used to assist in diagnosis, management and counseling for patients.

  9. Complete dissection of the Hb(64-76) determinant using T helper 1, T helper 2 clones, and T cell hybridomas

    DEFF Research Database (Denmark)

    Evavold, B D; Williams, S G; Hsu, B L

    1992-01-01

    We have generated cloned Th1 cells, Th2 cells, and T cell hybridomas specific for the single immunogenic peptide from the beta-chain of murine hemoglobin (Hb(64-76)). The availability of these various types of T cells provided us an unique opportunity to examine and dissect the T cell response...... to an immunogenic peptide. A panel of altered Hb peptides was made by replacing each amino acid in the Hb peptide (positions 64-76) with a conservative amino acid substitution or an alanine. Although none of the eleven T cell clones and hybridomas tested exhibited the same pattern of reactivity to the substituted...... Hb peptides, some general features were identified for all T cell responses. The primary T cell contact residue of Hb(64-76) was shown to be asparagine 72. For every Hb(64-76) specific T cell, no activation was observed using a peptide containing the conservative substitution of a glutamine...

  10. A conservative region of the mercuric reductase gene (merA) as a molecular marker of bacterial mercury resistance Região conservada do gene da mercúrio redutase (merA) como marcador molecular da resistência bacteriana ao mercúrio

    OpenAIRE

    Adriana Sotero-Martins; Michele Silva de Jesus; Michele Lacerda; Josino Costa Moreira; Ana Luzia Lauria Filgueiras; Paulo Rubens Guimarães Barrocas

    2008-01-01

    The most common bacterial mercury resistance mechanism is based on the reduction of Hg(II) to Hg0, which is dependent of the mercuric reductase enzyme (MerA) activity. The use of a 431 bp fragment of a conservative region of the mercuric reductase (merA) gene was applied as a molecular marker of this mechanism, allowing the identification of mercury resistant bacterial strains.O mecanismo de resistência bacteriana ao mercúrio mais comum é baseada na redução do Hg(II) a Hg0, através da ativida...

  11. HbA1c and Glycated Albumin Levels Are High in Gastrectomized Subjects with Iron-Deficiency Anemia.

    Science.gov (United States)

    Inada, Shinya; Koga, Masafumi

    2017-01-01

    We report that glycated albumin (GA) is higher relative to HbA1c in non-diabetic, gastrectomized subjects without anemia, and thus is a sign of oxyhyperglycemia. It is known that gastrectomized subjects are prone to iron-deficiency anemia (IDA), and that the HbA1c levels of subjects with IDA are falsely high. In the present study, the HbA1c and GA levels of gastrectomized subjects with IDA were compared with gastrectomized subjects without anemia. Seven non-diabetic gastrectomized subjects with IDA were enrolled in the present study. Twenty-eight non-diabetic gastrectomized subjects without anemia matched with the subjects with IDA in terms of age, gender, and body mass index were used as the controls. Although there were no significant differences in fasting plasma glucose and OGTT 2-hour plasma glucose (2-h PG) between the two groups, the HbA1c and GA levels in gastrectomized subjects with IDA were significantly higher than the controls. For all of the gastrectomized subjects (n=35), ferritin exhibited a significant negative correlation with HbA1c and GA, and a significant positive correlation with 2-h PG. In addition, the HbA1c and GA levels exhibited a significant negative correlation with the mean corpuscular hemoglobin and hemoglobin. The HbA1c and GA levels in gastrectomized subjects with IDA were significantly higher than those in controls. The high GA levels are attributed to a tendency in which patients with total gastrectomy, who are prone to IDA, are susceptible to postprandial hyperglycemia and reactive hypoglycemia, which in turn leads to large fluctuations in plasma glucose. © 2017 by the Association of Clinical Scientists, Inc.

  12. Translating HbA1c measurements into estimated average glucose values in pregnant women with diabetes

    DEFF Research Database (Denmark)

    Law, Graham R; Gilthorpe, Mark S; Secher, Anna L

    2017-01-01

    AIMS/HYPOTHESIS: This study aimed to examine the relationship between average glucose levels, assessed by continuous glucose monitoring (CGM), and HbA1c levels in pregnant women with diabetes to determine whether calculations of standard estimated average glucose (eAG) levels from HbA1c measureme...

  13. How can point-of-care HbA1c testing be integrated into UK primary care consultations? - A feasibility study.

    Science.gov (United States)

    Hirst, J A; Stevens, R J; Smith, I; James, T; Gudgin, B C; Farmer, A J

    2017-08-01

    Point-of-care (POC) HbA1c testing gives a rapid result, allowing testing and treatment decisions to take place in a single appointment. Trials of POC testing have not been shown to improve HbA1c, possibly because of how testing was implemented. This study aimed to identify key components of POC HbA1c testing and determine strategies to optimise implementation in UK primary care. This cohort feasibility study recruited thirty patients with type 2 diabetes and HbA1c>7.5% (58mmol/mol) into three primary care clinics. Patients' clinical care included two POC HbA1c tests over six months. Data were collected on appointment duration, clinical decisions, technical performance and patient behaviour. Fifty-three POC HbA1c consultations took place during the study; clinical decisions were made in 30 consultations. Five POC consultations with a family doctor lasted on average 11min and 48 consultations with nurses took on average 24min. Five POC study visits did not take place in one clinic. POC results were uploaded to hospital records from two clinics. In total, sixty-three POC tests were performed, and there were 11 cartridge failures. No changes in HbA1c or patient behaviour were observed. HbA1c measurement with POC devices can be effectively implemented in primary care. This work has identified when these technologies might work best, as well as potential challenges. The findings can be used to inform the design of a pragmatic trial to implement POC HbA1c testing. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  14. HbA1c variability in type 2 diabetes is associated with the occurrence of new-onset albuminuria within three years.

    Science.gov (United States)

    Dorajoo, Sreemanee Raaj; Ng, Joceline Shi Ling; Goh, Jessica Hui Fen; Lim, Su Chi; Yap, Chun Wei; Chan, Alexandre; Lee, Joyce Yu Chia

    2017-06-01

    To evaluate the association between HbA1c coefficient of variation (HbA1c-CV) and 3-year new-onset albuminuria risk. A retrospective cohort study involving 716 normoalbuminuric type 2 diabetes patients was conducted between 2010 and 2014. HbA1c-CV was used to categorize patients into low, moderate or high variability groups. Multivariate logistic models were constructed and validated. Integrated discrimination (IDI) and net reclassification (NRI) improvement indices were used to quantify the added predictive value of HbA1c-CV. The mean age of our cohort was 56.1±12.9years with a baseline HbA1c of 8.3±1.3%. Over 3-years of follow-up, 35.2% (n=252) developed albuminuria. An incremental risk of albuminuria was observed with moderate (6.68-13.43%) and high (above 13.44%) HbA1c-CV categories demonstrating adjusted odds ratios of 1.63 (1.12-2.38) and 3.80 (2.10-6.97) for 3-year new-onset albuminuria, respectively. Including HbA1c-CV for 3-year new-onset albuminuria prediction improved model discrimination (IDI: 0.023, NRI: 0.293, pHbA1c-CV improves 3-year prediction of new-onset albuminuria. Together with mean HbA1c, baseline urine albumin-to-creatinine ratio and presence of hypertension, accurate 3-year new-onset albuminuria prediction may be possible. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. The Natural History of Hb S/Hereditary Persistence of Fetal Hemoglobin in 13 Children from the State of Minas Gerais, Brazil.

    Science.gov (United States)

    Belisário, André R; Sales, Rahyssa R; Silva, Célia M; Velloso-Rodrigues, Cibele; Viana, Marcos Borato

    2016-06-01

    Children with Hb S (HBB: c.20A > T)/hereditary persistence of fetal hemoglobin (Hb S/HPFH) have a mild clinical phenotype, but some complications have been reported. The natural history of Hb S/HPFH in children from the State of Minas Gerais, Brazil newborn cohort is described. Clinical and hematological data regarding participants' phenotypes were retrieved from medical records. The HPFH-1, HPFH-2, and HPFH-3 and α-thalassemia (α-thal) deletions were detected by gap-polymerase chain reaction (gap-PCR). Thirteen children were included, nine (69.2%) had the Hb S/HPFH-2 deletion, and four (30.8%) had Hb S/HPFH-1 deletion; 11 children (84.6%) had αα/αα, and two (15.4%) carried the αα/-α(3.7) (rightward) deletion. The mean concentration of total hemoglobin (Hb) and Hb F was 12.52 ± 0.56 g/dL and 42.31% ± 1.97%, respectively. Mild microcytosis and hypochromia were observed. We found acute clinical manifestations of sickle cell disease, such as acute chest syndrome (ACS) and acute pain crisis in four children; nine (69.2%) children were completely asymptomatic during the follow-up period. All children were classified as having low-risk transcranial Doppler (TDC). In conclusion, children with Hb S/HPFH have a mild clinical phenotype of sickle cell disease, although acute clinical manifestations may occur. High Hb F levels and absence of anemia are common hematological characteristics.

  16. Alcohol consumption reduces HbA1c and glycated albumin concentrations but not 1,5-anhydroglucitol.

    Science.gov (United States)

    Inada, Shinya; Koga, Masafumi

    2017-11-01

    Background The effect of alcohol consumption on glycaemic control indicators is not well known. In this study, we studied the effect of alcohol consumption on the plasma glucose and glycaemic control indicators in non-diabetic men. Methods The study enrolled 300 non-diabetic men who received a complete medical checkup (age: 52.8 ± 6.5 years, body mass index: 24.4 ± 2.8 kg/m 2 ). The subjects were divided into four groups by the amount of alcohol consumed, and the plasma glucose, HbA1c, glycated albumin (GA) and 1,5-anhydroglucitol (1,5-AG) concentrations of the groups were compared. Results As the level of alcohol consumption increased, significantly high concentrations of fasting plasma glucose (FPG) were observed, and the oral glucose tolerance test 2-h plasma glucose concentrations tended to rise. While no significant effect of alcohol consumption on HbA1c, 1,5-AG, and the 1,5-AG/FPG ratio was observed, the HbA1c/FPG ratio, GA and the GA/FPG ratio exhibited significantly low values as the level of alcohol consumption increased. In stepwise multivariate regression analysis, alcohol consumption was a significant negative independent variable for HbA1c and GA, but not for 1,5-AG. Conclusions As the level of alcohol consumption increased, the plasma glucose concentrations rose, but the HbA1c and GA concentrations were lower compared with the plasma glucose concentrations. These findings suggest that alcohol consumption may reduce HbA1c and GA concentrations, but not 1,5-AG.

  17. Diabetes distress is more strongly associated with HbA1c than depressive symptoms in adolescents with type 1 diabetes

    DEFF Research Database (Denmark)

    Hagger, Virginia; Hendrieckx, Christel; Cameron, Fergus

    2018-01-01

    BACKGROUND: Glycated hemoglobin (HbA1c) is higher during adolescence than at any other life stage. Some research among adolescents indicates that depressive symptoms are associated with suboptimal HbA1c. However, research among adults suggests diabetes distress is a stronger predictor of HbA1c th...

  18. HbA1c Outcomes in Patients Treated With Canagliflozin Versus Sitagliptin in US Health Plans.

    Science.gov (United States)

    Thayer, Sarah; Aguilar, Richard; Korrer, Stephanie; Chow, Wing

    2017-10-01

    Clinical trial evidence supports greater glycemic control with canagliflozin than with sitagliptin. The objective of this study was to provide real-world evidence comparing outcomes in routine clinical practice among patients initiating each medication. With the use of a health care administrative database, patients initiating canagliflozin were compared with patients initiating sitagliptin (first prescription fill as index date). Baseline (6 months before index date) demographic and clinical (eg, comorbidities and diabetes-related complications) characteristics were compared, and propensity score matching was used to control for baseline differences between cohorts. Outcomes included change in glycosylated hemoglobin (HbA 1c ) and persistence with medication over a 9-month period after index date. Before matching, the canagliflozin cohort (N = 3993) was younger than the sitagliptin cohort (N = 12,153) and was composed of fewer women and Medicare Advantage enrollees, with lower mean baseline comorbidity scores (all p < 0.001). Before matching, the canagliflozin cohort (valid n = 1482) had a significantly (p < 0.001) higher baseline HbA 1c (8.60) than the sitagliptin cohort (valid n = 3697; HbA 1c , 8.32). After matching (n = 1472 per cohort), patients were well balanced on baseline characteristics, and HbA 1c values were not significantly different (p = 0.634) between the cohorts. Patients initiating canagliflozin had greater reductions in HbA 1c than patients in the sitagliptin cohort (-0.93% versus -0.57%, respectively; p = 0.004), with similar mean (median) time from index date to follow-up HbA 1c of 185.4 (199.0) and 184.3 (190.5) days, respectively (p = 0.802). Only 29.8% of canagliflozin patients discontinued during follow-up compared with 41.5% of sitagliptin patients (p < 0.001); the average days of persistence on index therapy was longer for canagliflozin patients (152 days) than for sitagliptin patients (139 days; p < 0.001). In this observational study

  19. Dinâmica molecular ab initio:aplicações ao estudo de propriedades electrónicas de sistemas moleculares

    OpenAIRE

    Martiniano, Hugo Filipe de Mesquita Costa, 1978-

    2013-01-01

    Tese de doutoramento, Química (Química-Física), Universidade de Lisboa, Faculdade de Ciências, 2013 O método da dinâmica molecular ab initio exibe vantagens significativas para o estudo da estrutura e propriedades electrónicas de sistemas moleculares complexos. No entanto, uma das suas desvantagens é o elevado custo computacional, quando comparado com os métodos de dinâmica molecular clássicos. Um dos modos de resolver este problema é adoptar uma abordagem sequencial, na qual a dinâmica é ...

  20. Visceral fat area is associated with HbA1c but not dialysate-related glucose load in nondiabetic PD patients

    Science.gov (United States)

    Ho, Li-Chun; Yen, Chung-Jen; Chao, Chia-Ter; Chiang, Chih-Kang; Huang, Jenq-Wen; Hung, Kuan-Yu

    2015-08-01

    Factors associated with increased visceral fat area (VFA) have been well documented in the general population but rarely explored in nondiabetic individuals on peritoneal dialysis (PD). As glycosylated hemoglobin (HbA1c) is positively correlated with VFA in diabetic patients, we hypothesized that the same correlation would exist in nondiabetic PD patients. We enrolled 105 nondiabetic patients who had undergone chronic PD for more than 3 months. Each subject underwent an abdominal computed tomography (CT) scan, and the umbilicus cut was analyzed for VFA. VFA values, corrected for body mass index and subjected to natural logarithm transformations, were examined to determine whether they were correlated with HbA1c and other parameters. PD dialysates prescribed at the time of enrollment were recorded to calculate glucose load. We found that when 105 nondiabetic PD patients were classified according to tertiles of HbA1c, higher HbA1c was associated with larger VFA. Multiple linear regression analysis revealed that HbA1c was an independent determinant of VFA, while glucose load and other PD-specific factors were not. In summary, HbA1c, but not PD-related glucose load, was positively correlated with VFA in nondiabetic PD patients, suggesting clinical utility of HbA1c in the PD population.

  1. Cutoff value of HbA1c for predicting diabetes and prediabetes in a Chinese high risk population aged over 45.

    Science.gov (United States)

    Zhang, Ruyi; Wang, Jiao; Luo, Jinhua; Yang, Xiaoyan; Yang, Rui; Cai, Dehong; Zhang, Hua

    2015-01-01

    To evaluate the cutoff value of HbA1c for predicting diabetes and prediabetes in a Chinese high risk population aged over 45. A total of 619 people aged over 45 without diabetes were randomly recruited to complete Finnish Diabetes Risk Score (FINDRISC) questionnaire. 208 high-risk individuals (defined by Diabetes Risk Score >=9) had OGTT and HbA1c determined at the same time. In a Chinese population aged over 45, the best cutoff value of HbA1c for detecting diabetes and prediabetes was 5.8% and 5.4% respectively. The area under the receiver operating characteristic (AUROC) curve of HbA1c for detecting diabetes was 0.85 (95% CI: 0.80-0.90) and prediabetes was 0.62 (95% CI: 0.54-0.70). The combined use of HbA1c and fasting blood glucose (FPG) had larger AUROC than HbA1c alone (0.88, 95%CI: 0.83-0.92 in detecting diabetes vs 0.75, 95% CI: 0.67-0.82 in prediabetes), and had a higher sensitivity in predicting diabetes and higher specificity and positive predictive value (PPV) in predicting prediabetes. However, the AUROC between HbA1c alone and combined use in predicting diabetes was not significantly different (p=0.173). FINDRISC is feasible tool to screen people who are at high risk of diabetes. The cutoff values of HbA1c to diagnose diabetes and prediabetes in a Chinese high risk population aged over 45 were 5.8% and 5.4%, respectively. The sensitivity and specificity of HbA1c for detecting diabetes and prediabetes was relatively low, so that the combined use of HbA1c and FPG may be more effective in prediction.

  2. The relationships among iron supplement use, Hb concentration and linear growth in young children: Ethiopian Demographic and Health Survey.

    Science.gov (United States)

    Mohammed, Shimels Hussien; Esmaillzadeh, Ahmad

    2017-11-01

    Growth faltering and anaemia remain unacceptably high among infants and young children in Ethiopia. In this study, we investigated the relationships among Fe supplement use (ISU), Hb concentration and linear growth, hypothesising positive relationships between ISU and Hb, ISU and linear growth and Hb and linear growth. We used a nationally representative data of 2400 children aged 6-24 months from the Ethiopian Demographic and Health Survey (EDHS) 2011, conducted following a stratified, two-stage cluster sampling. We examined the links by Pearson's correlation, bivariate and multivariate linear regression analyses and reported adjusted estimates. We found that ISU was not significantly associated with either Hb (β=1·09; 95 % CI -2·73, 5·01, P=0·567) or linear growth (β=0·07; 95 % CI -0·06, 0·21, P=0·217). We found a positive, however, weak, correlation between Hb and linear growth (r 0·09; 95 % CI 0·06, 0·11, PHb predicted linear growth independent of a variety dietary and non-dietary factors (β=0·08; 95 % CI 0·04, 0·11, PHb; age, birth type, size at birth, sex, breast-feeding duration, dietary diversity and deworming were independently associated with linear growth, indicating that Hb and linear growth are multifactorial with both nutritional and non-nutritional factors implicated. Further studies, with better design and exposure assessment, are warranted on the relation of ISU with Hb or linear growth.

  3. The Stricter the Better? The Relationship between Targeted HbA1c Values and Metabolic Control of Pediatric Type 1 Diabetes Mellitus.

    Science.gov (United States)

    Braun, Marcin; Tomasik, Bartlomiej; Wrona, Ewa; Fendler, Wojciech; Jarosz-Chobot, Przemyslawa; Szadkowska, Agnieszka; Zmysłowska, Agnieszka; Wilson, Jayne; Mlynarski, Wojciech

    2016-01-01

    It remains unclear how HbA1c recommendations influence metabolic control of paediatric patients with type 1 diabetes mellitus. To evaluate this we compared reported HbA1c with guideline thresholds. We searched systematically MEDLINE and EMBASE for studies reporting on HbA1c in children with T1DM and grouped them according to targeted HbA1c obtained from regional guidelines. We assessed the discrepancies in the metabolic control between these groups by comparing mean HbA1c extracted from each study and the differences between actual and targeted HbA1c. We included 105 from 1365 searched studies. The median (IQR) HbA1c for the study population was 8.30% (8.00%-8.70%) and was lower in "6.5%" than in "7.5%" as targeted HbA1c level (8.20% (7.85%-8.57%) versus 8.40% (8.20%-8.80%); p = 0.028). Median difference between actual and targeted HbA1c was 1.20% (0.80%-1.70%) and was higher in "6.5%" than in "7.5%" (1.70% (1.30%-2.07%) versus 0.90% (0.70%-1.30%), resp.; p HbA1c levels being closer to the therapeutic goal, but the actual values are still higher than those observed in the "6.5%" group. A meta-analysis of raw data from national registries or a prospective study comparing both approaches is warranted as the next step to examine this subject further.

  4. 77 FR 5566 - Notice of Availability of the Final EIS for the HB In-Situ Solution Mine Project, Eddy County...

    Science.gov (United States)

    2012-02-03

    ...] Notice of Availability of the Final EIS for the HB In-Situ Solution Mine Project, Eddy County, New Mexico... Statement (Final EIS) for the HB In-Situ Solution Mine Project, and by this notice is announcing its... the Federal Register. ADDRESSES: Copies of the HB In-Situ Solution Mining EIS are available for public...

  5. KADAR HbA1c DAN RASIO LIPID PADA WANITA DEWASA DENGAN OBESITAS SENTRAL

    Directory of Open Access Journals (Sweden)

    Lisa Sudaryanto

    2016-06-01

    Full Text Available Central obesity was accumulation of fat in the abdominal region. Many studies showed correlations between central obesity and cardiovascular diseases, e.g. diabetes and dyslipidemia.  This study was conducted to know the difference between HbA1c and lipid profil between the women with and without central obesity. This study was an analytic observational study with cross-sectional design. Subjects of 52 respondents were healthy adult women staff in campus I, II, III Sanata Dharma University in Yogyakarta and selected using purposive sampling technique. The data of waist circumference, pelvic/hip circumference, HbA1c and lipid profile were collected among the subjects and analyzed with computer with 95% confidence interval. The results of this study showed HbA1c levels and lipid profile were different between the women with and without central obesity, although the difference was not statistically significant.

  6. Baixa resposta da vacinação intradérmica contra hepatite B em pacientes incidentes em hemodiálise

    Directory of Open Access Journals (Sweden)

    Regina H. Medeiros

    2011-03-01

    Full Text Available INTRODUÇÃO: A hepatite B pode evoluir para cirrose e hepatocarcinoma. Sua prevalência estimada é de 3,2% em pacientes em hemodiálise (HD. A vacina para hepatite B (HB, quando aplicada por via intramuscular (IM em pacientes com insuficiência renal crônica fase V, frequentemente não induz produção adequada de anticorpos. A injeção intradérmica (ID foi sugerida como sendo o método de inoculação mais eficiente. OBJETIVO: Comparar a resposta imune à injeção IM ou ID da vacina em indivíduos em HD. PACIENTES E MÉTODOS: Trinta e um pacientes incidentes em HD foram randomizados alternativamente para vacinação contra HB via IM ou ID. Dezesseis foram designados aleatoriamente para receber vacina IM (40 mg/dose e 15 ID (4mg /dose. Os níveis de anticorpos de superfície do vírus da hepatite B, parâmetros hematimétricos, ureia sérica, e Kt/V foram avaliados mensalmente. Proteína-C reativa, paratormônio, ferritina, aminotransferases e albumina foram avaliados antes da inoculação inicial e seis meses após a mesma. RESULTADOS: Os níveis de uréia foram maiores no grupo ID (P(1 = 0,031; os níveis de ferritina foram mais elevados no IM (P(2 = 0,037. Houve tendência a aumento nos níveis de proteína C reativa no grupo ID. A avaliação do Comitê de Monitoramento de Segurança dos indivíduos expostos recomendou a suspensão do estudo já que a inoculação por via IM converteu 62,5% e a ID converteu apenas 13,3% dos pacientes expostos. CONCLUSÃO: Com a metodologia utilizada, os resultados da vacina contra HB aplicada por via ID foi inferior à inoculação IM. Tais resultados podem ser decorrentes das doses inoculadas ou de outros fatores, como inflamação.

  7. HbA1c monitoring interval in patients on treatment for stable type 2 diabetes. A ten-year retrospective, open cohort study.

    Science.gov (United States)

    Ohde, Sachiko; Deshpande, Gautam A; Yokomichi, Hiroshi; Takahashi, Osamu; Fukui, Tsuguya; Yamagata, Zentaro

    2018-01-01

    [Aims] This study aims to suggest an informative interval for HbA1c in DM patients with stable glycemic control, based on test characteristics of the HbA1C assay using the signal-to-noise ratio method. [Methods] This was a retrospective, open cohort study. Data were collected between January 2005 to December 2014 at a tertiary-level community hospital in Japan. All adult patients aged under 75 years, with stable glycemic control on a first pharmaceutical regimen for Type II diabetes, and at least two HbA1c measurements after they achieved glycemic stability, were included in the analysis. We defined stable glycemic control as HbA1c HbA1c. The screening interval for HbA1c was defined as informative when the signal-to-noise ratio exceeded 1. [Results] Among 1066 adults with diabetes, 639 patients (18.5%) were identified as achieving stable glycemic control (511 male (67.3%)), with a mean HbA1c (SD) of 6.4 (0.4)% (46 mmol/mol). Patients with stable glycemic control increase their HbA1c 0.27% (3 mmol/mol) every year while HbA1c has 0.32% (3.5 mmol/mol) noise, as testing characteristics. Signal exceeds noise after 1.2 years (95%CI: 0.9-1.6). [Conclusion] Once patients achieve stable glycemic control at their HbA1c goal, an informative interval for HbA1c monitoring is once every year. Current guidelines, which suggest testing every six months, may contribute to substantial over-testing. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  8. Evaluating new HbA1c methods for adoption by the IFCC and NGSP reference networks using international quality targets.

    Science.gov (United States)

    Lenters-Westra, Erna; English, Emma

    2017-08-28

    As a reference laboratory for HbA1c, it is essential to have accurate and precise HbA1c methods covering a range of measurement principles. We report an evaluation of the Abbott Enzymatic (Architect c4000), Roche Gen.3 HbA1c (Cobas c513) and Tosoh G11 using different quality targets. The effect of hemoglobin variants, other potential interferences and the performance in comparison to both the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) and the National Glycohemoglobin Standardization Program (NGSP) reference systems was assessed using certified evaluation protocols. Each of the evaluated HbA1c methods had CVs HbA1c. Partly based on the result of this study, the Abbott Enzymatic method on the Architect c4000 and the Roche Gen.3 HbA1c on the Cobas c513 are now official, certified IFCC and NGSP SRMPs in the IFCC and NGSP networks. Sigma metrics quality criteria presented in a graph distinguish between good and excellent performance.

  9. Use of HbA1c to diagnose type 2 diabetes mellitus among high risk Sri Lankan adults.

    Science.gov (United States)

    Herath, H M M; Weerarathna, T P; Dahanayake, M U; Weerasinghe, N P

    Even though, glycosylated hemoglobin (HbA1c) was found to be effective in predicting diabetes especially in Caucasians there is limited evidence of its diagnostic utility in high risk Sri Lankan adults. This study aimed to determine the optimal HbA1c cut-off points for detecting diabetes in a high risk population in Sri Lanka. This community based study consisted of 254 previously healthy adults with history of diabetes in one or more first-degree relatives. Fasting plasma glucose (FPG) , glucose tolerance test (GTT) and HbA1c were measured in all and GTT was used as a reference to diagnose diabetes. Receiver operating characteristic curve was created to find the optimum HbA1c cut-off value to predict diabetes. Prevalence of diabetes was 12.2% (n=31) with FPG and 16.1% (n=41) with GTT. Prevalence rose to 27.6% (PHbA1c with cut-off of ≥6.5% was used as the diagnostic test. The ROC curves showed the HbA1c threshold of 6.3% provided the optimum balance between sensitivity (80.5%) and specificity (79%). In compared to GTT, FPG had only a modest sensitivity (65%) in diagnosing diabetes in this high risk population. Our study showed that optimum HbA1C cut-off for detecting diabetes was 6.3% and it had better sensitivity, but lower specificity than FPG. This study further showed that the prevalence of diabetes would become double if HbA1c is used over FPG to screen this high risk population. Copyright © 2016 Diabetes India. Published by Elsevier Ltd. All rights reserved.

  10. One-Hour Postload Hyperglycemia Confers Higher Risk of Hepatic Steatosis to HbA1c-Defined Prediabetic Subjects.

    Science.gov (United States)

    Fiorentino, Teresa Vanessa; Andreozzi, Francesco; Mannino, Gaia Chiara; Pedace, Elisabetta; Perticone, Maria; Sciacqua, Angela; Perticone, Francesco; Sesti, Giorgio

    2016-11-01

    Individuals with glycated hemoglobin (HbA1c)-defined prediabetes (HbA1c value of 5.7-6.4%) and 1-hour plasma glucose ≥155 mg/dL during an oral glucose tolerance test have an increased risk of developing type 2 diabetes. To evaluate the degree to which HbA1c-defined prediabetes and 1-hour postload glucose ≥155 mg/dL individually and jointly associate with hepatic steatosis and related biomarkers. A cross-sectional analysis was performed on 1108 White individuals. Ambulatory care. Anthropometric and metabolic characteristics including hepatic steatosis assessed by ultrasonography. Compared with the normal group (HbA1c prediabetic and diabetic individuals exhibit higher values of fasting, 1-hour, and 2-hour postload glucose; fasting and 2-hour postload insulin; triglycerides; uric acid; homeostasis model of assessment for insulin resistance; liver insulin resistance index; liver enzymes; and inflammatory biomarkers; and lower levels of high-density lipoprotein cholesterol and IGF-1. Prediabetic and diabetic subjects have increased risk of hepatic steatosis (1.5- and 2.46-fold, respectively). Stratifying participants according to HbA1c and 1-hour postload glucose, we found that individuals with HbA1c-defined prediabetes and 1-hour postload glucose ≥155 mg/dL have significantly higher risk of hepatic steatosis as compared with individuals with HbA1c-defined prediabetes but 1-hour postload glucose prediabetes and 1-hour postload glucose ≥155 mg/dL exhibit higher values of liver enzymes; fasting, 1-hour, and 2-hour postload glucose; insulin; triglycerides; uric acid; and inflammatory biomarkers; and lower levels of high-density lipoprotein and IGF-1. These data suggest that a value of 1-hour postload glucose ≥155 mg/dL may be helpful to identify a subset of individuals within HbA1c-defined glycemic categories at higher risk of hepatic steatosis.

  11. HbA1c as a Screening tool for Ketosis in Patients with Type 2 Diabetes Mellitus

    Science.gov (United States)

    Zhu, Bing; Bu, Le; Zhang, Manna; Gusdon, Aaron M.; Zheng, Liang; Rampersad, Sharvan; Li, Jue; Qu, Shen

    2016-01-01

    Ketosis in patients with type 2 diabetes mellitus (T2DM) is overlooked due to atypical symptoms. The objective of this study is to evaluate the value of hemoglobin A1c (HbA1c) as a screening tool for ketosis in T2DM patients. This retrospective study consisted of 253 T2DM patients with ketosis at Shanghai 10th People’s Hospital during a period from January 1, 2011 to June 30, 2015. A control group consisted of 221 T2DM patients without ketosis randomly selected from inpatients during the same period. Receiver operating characteristic curve (ROC) analysis was used to examine the sensitivity and specificity of HbA1c as an indicator for ketosis. Higher HbA1c levels were correlated with ketosis. In patients with newly diagnosed T2DM, the area under the curve (AUC) was 0.832, with 95% confidence interval (CI) 0.754–0.911. The optimal threshold was 10.1% (87 mmol/mol). In patients with previously diagnosed T2DM, the AUC was 0.811 (95% CI: 0.767–0.856), with an optimal threshold of 8.6% (70 mmol/mol). HbA1c is a potential screening tool for ketosis in patients with T2DM. Ketosis is much more likely with HbA1c values at ≥10.1% in patients with newly diagnosed T2DM and HbA1c values at ≥8.6% in patients with previously diagnosed T2DM. PMID:28009017

  12. Hb Nouakchott [α114(GH2)Pro→Leu; HBA1: c.344C>T], A Second and Third Case Described in Two Unrelated Dutch Families.

    Science.gov (United States)

    Pondman, Kirsten M; Brinkman, Jacoline W; van der Straaten, Hanneke M; Stroobants, An K; Harteveld, Cornelis L

    2018-01-01

    We report two families, members of which are carriers of a hemoglobin (Hb) variant previously described as Hb Nouakchott [α114(GH2)Pro→Leu; HBA1: c.344C>T; p.Pro115Leu]. In the first family of Dutch origin, the proband, a 32-year-old male and his 65-year-old father, were both carriers of Hb Nouakchott. Of the second family we tested, only the proband, a 56-year-old Dutch female was a Hb Nouakchott carrier. Hematological analyses of these cases showed the anomaly behaves as a silent Hb variant without clinical consequences. The Hb variant remained unnoticed using high performance liquid chromatography (HPLC), while an additional peak was detected by capillary electrophoresis (CE). These independent findings of Hb Nouakchott indicate that this Hb variant might not be very rare, but simply remains under diagnosed depending on the Hb separation technique used.

  13. Ethnic dependent differences in diagnostic accuracy of glycated hemoglobin (HbA1c) in Canadian adults.

    Science.gov (United States)

    Booth, Ronald A; Jiang, Ying; Morrison, Howard; Orpana, Heather; Rogers Van Katwyk, Susan; Lemieux, Chantal

    2018-02-01

    Previous studies have shown varying sensitivity and specificity of hemoglobin A1c (HbA1c) to identify diabetes and prediabetes, compared to 2-h oral glucose tolerance testing (OGTT) and fasting plasma glucose (FPG), in different ethnic groups. Within the Canadian population, the ability of HbA1c to identify prediabetes and diabetes in First Nations, Métis and Inuit, East and South Asian ethnic groups has yet to be determined. We collected demographic, lifestyle information, biochemical results of glycemic status (FPG, OGTT, and HbA1c) from an ethnically diverse Canadian population sample, which included a purposeful sampling of First Nations, Métis, Inuit, South Asian and East Asian participants. Sensitivity and specificity using Canadian Diabetes Association (CDA) recommended cut-points varied between ethnic groups, with greater variability for identification of prediabetes than diabetes. Dysglycemia (prediabetes and diabetes) was identified with a sensitivity and specificity ranging from 47.1% to 87.5%, respectively in Caucasians to 24.1% and 88.8% in Inuit. Optimal HbA1c ethnic-specific cut-points for dysglycemia and diabetes were determined by receiver operating characteristic (ROC) curve analysis. Our sample showed broad differences in the ability of HbA1c to identify dysglycemia or diabetes in different ethnic groups. Optimal cut-points for dysglycemia or diabetes in all ethnic groups were substantially lower than CDA recommendations. Utilization of HbA1c as the sole biochemical diagnostic marker may produce varying degrees of false negative results depending on the ethnicity of screened individuals. Further research is necessary to identify and validate optimal ethnic specific cut-points used for diabetic screening in the Canadian population. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

  14. HbA1c in relation to incident diabetes and diabetes-related complications in non-diabetic adults at baseline.

    Science.gov (United States)

    Metcalf, Patricia Anne; Kyle, Cam; Kenealy, Tim; Jackson, Rod T

    2017-05-01

    We compared the utility of glycated hemoglobin (HbA 1c ) and oral glucose tolerance (oGTT) in non-diabetic patients for identifying incident diabetes; all-cause mortality; cardiovascular disease (CVD) mortality; CVD, coronary heart disease (CHD), and ischemic stroke events; and diabetes microvascular complications. Data from a New Zealand community setting were prospectively linked to hospitalization, mortality, pharmaceutical and laboratory test results data. After applying exclusion criteria (prior laboratory diagnosis or history of drug treatment for diabetes or hospitalization for diabetes or CVD event), there were 31,148 adults who had an HbA 1c and 2-h 75g oGTT. HbA 1c was measured by ion-exchange high-performance liquid chromatography, and glucose using a commercial enzymatic method. We compared glycemic measures and outcomes using multivariable Cox proportional hazards regression. The median follow-up time was 4years (range 0 to 13). The mean age was 57·6years and 53·0% were male. After adjusting for other glycemic measures (fasting glucose, 2-h glucose and/or HbA 1c where relevant) in addition to age, sex, ethnicity and smoking habit, the hazard ratios for incident diabetes and diabetes complications of retinopathy and nephropathy were highest for 2-h glucose levels, followed by HbA 1c and lastly by fasting glucose. However, all-cause mortality and CHD were significantly associated with HbA 1c concentrations only, and ischemic stroke and CVD events with 2-h glucose only. Circulatory complications showed a stronger association with HbA 1c . Apart from neuropathy, HbA 1c showed stronger associations with outcomes compared to fasting glucose and provides a convenient alternative to an oGTT. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. The Value of HbA1c and hs-CRP Combined Detection in Diagnosis of Diabetic Retinopathy%HbA1c、hs-CRP 联合检测诊断糖尿病视网膜病变的价值

    Institute of Scientific and Technical Information of China (English)

    李孝才; 孙学芬; 吴建霞; 马雪燕

    2016-01-01

    目的:探讨糖化血红蛋白(HbA1c)和高敏 C 反应蛋白(hs-CRP)联合检测诊断糖尿病视网膜病变的价值。方法:选择正常体检者(A 组)、糖尿病无视网膜病变者(B 组)、糖尿病视网膜病变者(C 组)各72例,采用离子交换液相层析法和胶乳增强免疫比浊法测定 HbA1c 及 hs-CRP。结果:无视网膜病变组和视网膜病变组的 HbA1c 和 hs-CRP(mg/L)含量均比健康对照组高,具有统计学意义(P0.05);但是 HbA1c +Hs-CRP 诊断糖尿病视网膜病变的特异为90.3%,分别与 HbA1c 和 hs-CRP 存在明显差异(P 0.05); but specific to the HbA1c of hs CRP in the diagnosis of diabetic retinopathy was 90.3%, respectively and hs CRP and HbA1c exist significant difference (P< 0.05). Conclusion:The detection of HBA1c and Hs-CRPis helpful to early detection of diabetic retinopathy, which can be used asmonitoring indicators for progress and treatment effect in type 2 diabetes mellitus patients.

  16. Acute viral hepatitis in adults. Comparison of the radioimmunoassay and counterimmunoelectrophoresis methods of detecting HB/sub s/Ag

    International Nuclear Information System (INIS)

    Wenzel, R.P.; Teates, C.D.; Galapon, Q.; Barczak, R.; Ling, C.M.; Overby, L.R.

    1975-01-01

    The radioimmunoassay (RIA) and counterimmunoelectrophoretic (CIE) methods were compared in detecting hepatitis B antigen (HB/sub s/Ag) in 407 acute and 336 convalescent sera of adults with viral hepatitis. The CIE method demonstrated that 41 percent of acute and 28 percent of 14- to 17-day serum specimens were HB/sub s/Ag-positive. The RIA method demonstrated seropositivity in 60 percent of acute and 56 percent of convalescent specimens (P less than .001). Eighty-four percent of coded specimens initially positive for HB/sub s/Ag by RIA were found to have subtype antigenic determinants d or y; 92 percent of the HB/sub s/Ag-negative controls were negative for subtype antigens, confirming the specificity of the RIA test. RIA subtyping data corroborated earlier work with immunodiffusion techniques. (U.S.)

  17. Muscle pathology in lower motor neuron paraplegia and h-b FES

    Directory of Open Access Journals (Sweden)

    Ugo Carraro

    2010-03-01

    Full Text Available After complete Spinal Cord Injury (SCI, causing complete disconnection between the muscle fibers and the nervous system, the denervated muscles become unexcitable with commercial electrical stimulators within several months and undergo severe atrophy and disorganization of contractile apparatus after 1-3 years. Years after the injury the surviving and regenerated myofibers are substituted with adipocytes and collagen. To counteract the progressive changes transforming muscle into an unexcitable tissue, we developed a novel therapy concept for paraplegic patients with complete lower motor neuron (LMN denervation of the lower extremities. The new stimulators for home-based functional electrical stimulation (h-b FES have been designed to reverse longstanding and severe atrophy of LMN denervated muscles by delivering high-intensity (up to 2,4 J and long-duration impulses (up to 150 ms able to elicit contractions of denervated skeletal muscle fibers in absence of nerve. Concurrent to the development of the stimulation equipment, specific clinical assessments and training strategies were developed at the Wilhelminenspital Wien, Austria. Main results of our clinical study on 20 patients, which completed a 2 years h-b FES program are: 1. significant +33% increase of muscle size and +75% of the mean diameter of muscle fibers, with striking improvements of the ultra-structural organization of contractile material; 2. recovery of the tetanic contractility with significant increase in muscle force output during electrical stimulation; 3. five subjects performed FES-assisted stand-up and stepping-in-place exercises;. 4. data from ultrastructural analyses indicating that the shorter the time span between SCI and the beginning of h-b FES, the larger were the number and the size of recovered fibers. The study demonstrates that h-b FES of permanent LMN denervated muscle is an effective home therapy that results in rescue of muscle mass, function and perfusion

  18. Marcação da Anexina V para imagem funcional da apoptose celular

    OpenAIRE

    Valente, Susana Catarina Monteiro

    2011-01-01

    Dissertação para obtenção do Grau de Mestre em Genética Molecular e Biomedicina O cancro colorrectal é a segunda principal causa de morte a nível mundial por neoplasia. A externalização da fosfatidilserina é um dos primeiros eventos da apoptose. Assim, o uso da Anexina V radiomarcada com 99mTecnécio torna-se num importante método de detecção e monitorização terapêutica de cancro in vivo. A 99mTc-HYNIC-Anexina V foi usada para detecção de apoptose em células do cancro colorrectal (WiDr) ...

  19. Complex Interaction of Hb Q-Thailand with α0- and β0-Thalassemia in a Chinese Family.

    Science.gov (United States)

    He, Sheng; Qin, Qian; Lin, Li; Chen, Qiuli; Yi, Shang; Wei, Honhwei; Du, Juan; Zheng, Chenguang; Qiu, Xiaoxia; Chen, Biyan

    2017-01-01

    Hb Q-Thailand [α74(EF3)Asp→His (α1); HBA1: c.223 G>C] is an abnormal hemoglobin (Hb), variant found mainly in China and Southeast Asian countries. The association of the α Q -Thailand allele with other globin gene disorders has important implications in diagnosis. Here, we report a hitherto undescribed condition of patients with a double heterozygosity for Hb Q-Thailand with α 0 -thalassemia (α 0 -thal) and in combination with β 0 -thalassemia (β 0 -thal) in a Chinese family. Our study will provide some clinical manifestations, laboratory diagnosis and genetic counseling for complex hemoglobinopathies.

  20. Do paradigma molecular ao impacto no prognóstico: uma visão da leucemia promielocítica aguda From the molecular model to the impact on prognosis: an overview on acute promyelocytic leukemia

    Directory of Open Access Journals (Sweden)

    Rafael Henriques Jácomo

    2008-02-01

    Full Text Available A leucemia promielocítica aguda (LPA é um modelo da aplicabilidade clínica dos conhecimentos moleculares fisiopatológicos. Caracteriza-se por alterações genéticas recorrentes que envolvem o gene do receptor alfa do ácido retinóico. A conseqüência é uma proteína com sensibilidade reduzida ao ligante, com bloqueio da diferenciação mielóide. Entretanto, doses suprafisiológicas do ácido all-trans-retinóico (ATRA são capazes de suplantar esta deficiência, e este é o princípio fundamental do tratamento da LPA, permitindo uma sobrevida livre de doença acima de 80% quando adequadamente tratada. Epidemiologicamente, difere dos demais subtipos de leucemia mielóide aguda por apresentar incidência predominante em adultos jovens e, aparentemente, maior incidência em países de colonização "latina". Contrastando com os excelentes resultados observados em países desenvolvidos, a mortalidade por LPA no Brasil ainda é alta, apesar da ampla disponibilidade das medicações no país.Acute promyelocytic leukemia (APL is a model of clinical applicability of the knowledge of molecular physiopathology. It is characterized by recurrent genetic involvement of the retinoic acid alpha receptor. The consequence is a protein with low sensibility to its ligand and a myeloid maturation arrest. However, higher doses of all-trans-retinoic acid (ATRA are able to supersede this deficiency and this is the mainstay of APL treatment leading to over 80% disease free survival, when adequately treated. Epidemiologically, it differs from other acute myeloid leukemia due to a higher incidence in young adults and in countries of "Latin" colonization. Differing from excellent results observed in developed countries, APL mortality in Brazil is still high, despite the wide availability of drugs.

  1. Role of HbA1c in post-partum screening of women with gestational diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Rickard Claesson

    2015-03-01

    Conclusion: Proposed thresholds of HbA1c had low diagnostic sensitivity. Combined with a fasting glucose test, the performance was no better than with using a fasting glucose test alone. Combining a fasting glucose test with a lower HbA1c cut-point may be an alternative approach for selection of women for an OGTT.

  2. Is there a role for HbA1c in predicting mortality and morbidity outcomes after coronary artery bypass graft surgery?

    Science.gov (United States)

    Tennyson, Charlene; Lee, Rebecca; Attia, Rizwan

    2013-01-01

    A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was is there a role for HbA1c in predicting morbidity and mortality outcomes after coronary artery bypass surgery? Eleven studies presented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. The studies presented analyse the relationship between preoperative HbA1c levels and postoperative outcomes following coronary artery bypass graft (CABG) in diabetic, non-diabetic or mixed patient groups. Four studies found significant increases in early and late mortality at higher HbA1c levels, regardless of a preoperative diagnosis of diabetes. One study demonstrated that 30-day survival outcomes were significantly worse in patients with previously undiagnosed diabetes and elevated HbA1c compared with those with good control [HbA1c >6%; odds ratio 1.53, confidence interval (CI) (1.24–1.91); P = 0.0005]. However, four studies of early mortality outcomes in diabetic patients only showed no significant differences between patients with normal and those with deranged HbA1c levels (P = 0.99). There were mixed reports on morbidity outcomes. Three studies identified a significant increase in infectious complications in patients with poorly controlled HbA1c, two of which were irrespective of previous diabetic status [deep sternal wound infection (P = 0.014); superficial sternal wound infection (P = 0.007) and minor infections (P = 0.006) in poorly controlled diabetics only]. Four studies presented outcomes for total length of stay (LOS). Three of these papers looked specifically at diabetic patients, of which two found no significant differences in length of stay between good and poor preoperative glycaemic control [LOS: P = 0.59 and 0.86 vs P HbA1c vs normal HbA1c was associated with prolonged stay in hospital and in

  3. Associations of HbA1c and fasting plasma glucose with incident diabetes: Implications for pre-diabetes thresholds in a Japanese population.

    Science.gov (United States)

    Nakagami, Tomoko; Tanaka, Yuki; Oya, Junko; Kurita, Moritoshi; Isago, Chisato; Hasegawa, Yukiko; Ito, Arata; Hirota, Naoki; Tsuzura, Reika; Uchigata, Yasuko

    2016-12-01

    This study assessed pre-diabetes (pre-DM) cutoffs for HbA1c and fasting plasma glucose (FPG) that were associated with an increased risk of incident DM. We evaluated 2267 non-diabetic Japanese health-check examinees (HbA1c: HbA1c of ≥6.5% (≥48mmol/mol), FPG of ≥7.0mmol/L, or physician-diagnosed DM. During 11047 person-years, we identified 99 incident DM cases (4.3%). The incidence of DM increased with increasing baseline HbA1c or FPG levels, and the change points (95% confidence intervals) were 5.7% (5.6-5.7%; 39mmol/mol [38-39mmol/mol]) for HbA1c and 5.5mmol/L (5.5-5.6mmol/L) for FPG. The adjusted hazard ratios (HRs) for incident DM per one standard deviation-increase in HbA1c and FPG were 5.5 (4.4-6.8) and 4.0 (3.2-4.8), respectively. The adjusted HRs for incident DM were significantly higher at HbA1c of 5.7-6.4% (39-46mmol/mol) or FPG of 5.5-6.9mmol/L, compared to HbA1c of HbA1c and 5.5mmol/L for FPG in this Japanese population. Copyright © 2016 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.

  4. Comparing risk profiles of individuals diagnosed with diabetes by OGTT and HbA1c

    DEFF Research Database (Denmark)

    Borg, R.; Vistisen, D.; Witte, D.R.

    2010-01-01

    Glycated haemoglobin (HbA(1c)) has been proposed as an alternative to the oral glucose tolerance test for diagnosing diabetes. We compared the cardiovascular risk profile of individuals identified by these two alternative methods.......Glycated haemoglobin (HbA(1c)) has been proposed as an alternative to the oral glucose tolerance test for diagnosing diabetes. We compared the cardiovascular risk profile of individuals identified by these two alternative methods....

  5. The Impact of HbA1c Testing on Total Annual Healthcare Expenditures Among Newly Diagnosed Patients with Diabetes.

    Science.gov (United States)

    Bhounsule, Prajakta; Peterson, Andrew M

    2015-09-01

    In 2010, diabetes was the seventh leading cause of death in the United States. Diabetes also imposes a huge financial burden on the US economy. In 2009, the American Diabetes Association International Expert Committee recommended the use of the glycated hemoglobin (HbA1c) test as a uniform diagnostic measure to identify patients with diabetes. Although HbA1c is a convenient diagnostic test, it is also more expensive than older tests and could, therefore, have an impact on patients' healthcare expenditures. To determine if HbA1c testing has an impact on total annual healthcare expenditures among newly diagnosed patients with diabetes and to analyze the factors that are associated with the total healthcare expenditures among diabetic patients before and after HbA1c was implemented as a standard diagnostic factor. This was an observational, retrospective, cross-sectional study. The Medical Expenditure Panel Survey-Household Component 2009 and 2011 databases were used to form the study cohort of patients with diabetes. The total mean healthcare expenditures among patients with diabetes formed the dependent variable. A proxy variable representing a diagnosis of diabetes with and without the use of HbA1c testing in 2009 and in 2011, respectively, formed the main independent variable along with demographic factors, comorbidities, and healthcare services utilization in both years. A generalized linear regression was conducted to determine the association of HbA1c testing with total diabetes-related healthcare expenditures. The mean total healthcare expenditure decreased in 2011 compared with 2009. The HbA1c test did not show an association with the total healthcare expenditures versus earlier diabetes-related diagnostic factors. The total expenditures were associated with private insurance, the incidence of a previous heart attack, prescription drug refills, inpatient hospital stays, home care, hospital discharges, and visits to outpatient providers and physicians in both

  6. Evaluation of glycated hemoglobin (HbA1c for diagnosing type 2 diabetes and prediabetes among Palestinian Arab population.

    Directory of Open Access Journals (Sweden)

    Akram T Kharroubi

    Full Text Available The purpose of the study is to compare the potential of HbA1c to diagnose diabetes among Palestinian Arabs compared to fasting plasma glucose (FPG. A cross-sectional sample of 1370 Palestinian men (468 and women (902 without known diabetes and above the age of 30 years were recruited. Whole blood was used to estimate HbA(1c and plasma for FPG and total lipid profile. Fasting plasma glucose was used as a reference to diagnose diabetes (≥ 126 mg/dL and prediabetes (100-125 mg/dL. The area under the receiver operating characteristic curve (AUC for HbA(1c was 81.9% to diagnose diabetes and 63.9% for prediabetes. The agreement between HbA(1c and diabetes as diagnosed by FPG was moderate (ĸ  =  0.498 and low with prediabetes (ĸ = 0.142. The optimal cut-off value for HbA1c to diagnose diabetes was ≥ 6.3% (45 mmol/mol. The sensitivity, specificity and the discriminant ability were 65.6% (53.1-76.3%, 94.5% (93.1-95.6%, 80.0% (72.8-87.3%, respectively. However, using cut-off value of ≥ 6.5% (48 mmol/mol improved specificity. At this cut-off value, the sensitivity, specificity and the discriminant ability were 57.4% (44.9-69.0%, 97.1% (96.0-97.9% and 77.3% (71.0-83.5%. For diagnosing prediabetes with HbA1c between 5.7-6.4% (39-46 mmol/mol, the sensitivity, specificity and the discriminant ability were 62.7% (57.1-67.9%, 56.3% (53.1-59.4% and 59.5% (56.3-62.5%, respectively. HbA(1c at cut-off value of ≥ 6.5% (48 mmol/mol by itself diagnosed 5.3% and 48.3% as having diabetes and prediabetes compared to 4.5% and 24.2% using FPG, respectively. Mean HbA(1c and FPG increase significantly with increasing body mass index. In conclusion, the ROC curves showed HbA1c could be used for diagnosing diabetes when compared to FPG but not for prediabetes in Palestinians Arabs even though only about 50% of the diabetic subjects were identified by the both HbA1c and FPG.

  7. Evidência molecular da ocorrência de um fitoplasma associado ao lenho mole da macieira

    OpenAIRE

    Ribeiro,Luiz Fernando Caldeira; Bedendo,Ivan Paulo; Sanhueza,Rosa Maria Valdebenito

    2007-01-01

    O lenho mole da macieira é uma doença relevante em diversas partes do mundo. Sintomas típicos desta doença têm sido observados em pomares instalados em estados do sul do território brasileiro desde a década de oitenta. Enxertia tem revelado a natureza infecciosa da doença e a observação de corpúsculos filamentosos no floema tem evidenciado possível associação com fitoplasma. No presente trabalho plantas com sintomas de lenho mole foram coletadas em pomar comercial, visando demonstrar a presen...

  8. A novel engineered VEGF blocker with an excellent pharmacokinetic profile and robust anti-tumor activity

    International Nuclear Information System (INIS)

    Liu, Lily; Yu, Haijia; Huang, Xin; Tan, Hongzhi; Li, Song; Luo, Yan; Zhang, Li; Jiang, Sumei; Jia, Huifeng; Xiong, Yao; Zhang, Ruliang; Huang, Yi; Chu, Charles C; Tian, Wenzhi

    2015-01-01

    Relatively poor penetration and retention in tumor tissue has been documented for large molecule drugs including therapeutic antibodies and recombinant immunoglobulin constant region (Fc)-fusion proteins due to their large size, positive charge, and strong target binding affinity. Therefore, when designing a large molecular drug candidate, smaller size, neutral charge, and optimal affinity should be considered. We engineered a recombinant protein by molecular engineering the second domain of VEGFR1 and a few flanking residues fused with the Fc fragment of human IgG1, which we named HB-002.1. This recombinant protein was extensively characterized both in vitro and in vivo for its target-binding and target-blocking activities, pharmacokinetic profile, angiogenesis inhibition activity, and anti-tumor therapeutic efficacy. HB-002.1 has a molecular weight of ~80 kDa, isoelectric point of ~6.7, and an optimal target binding affinity of <1 nM. The pharmacokinetic profile was excellent with a half-life of 5 days, maximal concentration of 20.27 μg/ml, and area under the curve of 81.46 μg · days/ml. When tested in a transgenic zebrafish embryonic angiogenesis model, dramatic inhibition in angiogenesis was exhibited by a markedly reduced number of subintestinal vessels. When tested for anti-tumor efficacy, HB-002.1 was confirmed in two xenograft tumor models (A549 and Colo-205) to have a robust tumor killing activity, showing a percentage of inhibition over 90% at the dose of 20 mg/kg. Most promisingly, HB-002.1 showed a superior therapeutic efficacy compared to bevacizumab in the A549 xenograft model (tumor inhibition: 84.7% for HB-002.1 versus 67.6% for bevacizumab, P < 0.0001). HB-002.1 is a strong angiogenesis inhibitor that has the potential to be a novel promising drug for angiogenesis-related diseases such as tumor neoplasms and age-related macular degeneration

  9. A Novel Variant with Positive Natural Selection Influenced Hb A2 Levels in Chinese Individuals with β-Thalassemia.

    Science.gov (United States)

    Yu, Shanjuan; Chen, Yang; Lai, Ketong; Dewan, Roma Kajal; He, Yunyan

    2017-05-01

    β-Thalassemia (β-thal) is the most common inherited hemolytic anemia worldwide. Elevated Hb A 2 is a mark of β-thal carriers. The aim of this study was to identify the pathogenic variants associated with the Hb A 2 levels. One thousand and thirty β-thal carriers were recruited for this study. Using positive natural expression quantitative trait loci (eQTL) analysis, a significant variant was selected. Genotyping for the rs231841 polymorphism was performed by the Sequenom MassARRAY IPLEX platform. All genetic association analyses were performed with the PLINK program. The linear regression analysis showed that rs231841 in the intron region of the potassium voltage-gated channel subfamily Q member 1 (KCNQ1) gene on chromosome 11p15 was significantly associated with Hb A 2 levels. The presence of the C allele was associated with elevated Hb A 2 levels. Our results suggest that rs231841 on the KCNQ1 gene with positive natural selection is related to Hb A 2 levels in Chinese β-thal carriers, and KCNQ1 is probably associated with the expression of the β-like globin gene cluster.

  10. Survey of lead and CO--Hb in inhabitants in general

    Energy Technology Data Exchange (ETDEWEB)

    Mishima, M.; Hitosugi, M.; Ishikawa, K.; Suzuki, T.

    1972-11-01

    To grasp the effects of air pollution on the human body in smaller cities, lead content and CO--Hb (carboxyhemoglobin) in blood were examined in inhabitants of Soka City, Saitama Prefecture, as well as the factors of living. The inhabitants are nonuniform as an occupational population, however, from the point of view that the work places are located in the same city they are considered to be uniform as an occupational population. In the city, the Pb content of air was 6, 2 to 5 and 1 microgram/cu m, respectively, in highly, moderately, and slightly polluted areas. The Pb content of blood of inhabitants in highly polluted areas in the city was on the arithmetical average - 15 micrograms/dl, and CO--Hb in the same individuals was 1.8% (2.6% in smokers and 1.2% in nonsmokers). These figures mean that the effect of air pollution was very slight in the inhabitants in this city.

  11. Contemporary risk estimates of three HbA1c variables in relation to heart failure following diagnosis of type 2 diabetes.

    Science.gov (United States)

    Skrtic, Stanko; Cabrera, Claudia; Olsson, Marita; Schnecke, Volker; Lind, Marcus

    2017-03-01

    We evaluated the association between glycaemic control and the risk of heart failure (HF) in a contemporary cohort of persons followed after diagnosis of type 2 diabetes (T2D). Persons with T2D diagnosed between 1998 and 2012 were retrieved from the Clinical Practice Research Data Link in the UK and followed from diagnosis until the event of HF, mortality, drop out from the database due to any other reason, or the end of the study on 1 July 2015. The association between each of three different haemoglobin A 1C (HbA 1c ) metrics and HF was estimated using adjusted proportional hazard models. In the overall cohort (n=94 332), the increased risk for HF per 1% (10 mmol/mol) increase in HbA 1c was 1.15 (95% CI 1.13 to 1.18) for updated mean HbA 1c , and 1.06 (1.04 to 1.07) and 1.06 (1.04 to 1.08) for baseline HbA 1c and updated latest HbA 1c , respectively. When categorised, the hazard risk (HR) for the updated mean HbA 1c in relation to HF became higher than for baseline and updated latest HbA 1c above HbA 1c levels of 9%, but did not differ at lower HbA 1c levels. The updated latest variable showed an increased risk for HbA 1c <6% (42 mmol/mol) of 1.16 (1.07 to 1.25), relative category 6-7%, while the HRs for updated mean and baseline HbA 1c showed no such J-shaped pattern. Hyperglycaemia is still a risk factor for HF in persons with T2D of similar magnitude as in earlier cohorts. Such a relationship exists for current glycaemic levels, at diagnosis and the overall level but the pattern differs for these variables. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  12. K2-EDTA and K3-EDTA Greiner Tubes for HbA1c Measurement.

    Science.gov (United States)

    Vrtaric, Alen; Filipi, Petra; Hemar, Marina; Nikolac, Nora; Simundic, Ana-Maria

    2016-02-01

    To determine whether K2-ethylenediaminetetraacetic acid (EDTA) and K3-EDTA Greiner tubes could be used interchangeably for glycosylated hemoglobin, type A1C (HbA1c) measurement via the Abbott Laboratories ARCHITECT chemiluminescent microparticle HbA1c assay on the ARCHITECT i2000SR immunoanalyzer at our university hospital. We drew blood from a total of 45 outpatients into plastic Greiner Vacuette tubes, some of which were lined with K2-EDTA and others with K3-EDTA anticoagulant. Data are presented as median and interquartile range values. We used the Wilcoxon test and Passing-Bablok regression for tube comparison. For K2-EDTA tubes median HbA1c concentration was 54 mmol/mol (41 to 71 mmol/mol) and for K3-EDTA tubes 56 mmol/mol (43 to 69 mmol/mol). There was no statistically significant difference between K2-EDTA and K3-EDTA (bias= -1.29 mmol/mol; P = 0.24). Passing-Bablok regression showed that there is no constant and proportional error: y = -0.23 (95% CI[-3.52 to 0.69]) + 1.00( 95% CI[0.98 to 1.06]) x. In this study, we provide evidence for the lack of any clinically and statistically significant bias between K2-EDTA and K3-EDTA HbA1c measurements. Thus, Greiner tubes lined with K2-EDTA and those lined with K3-EDTA can safely be used interchangeably to measure HbA1c via the Abbott Laboratories ARCHITECT assay. © American Society for Clinical Pathology, 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  13. The Glycated Albumin (GA) to HbA1c Ratio Reflects Shorter-Term Glycemic Control than GA: Analysis of Patients with Fulminant Type 1 Diabetes.

    Science.gov (United States)

    Koga, Masafumi; Inada, Shinya; Nakao, Taisei; Kawamori, Ryuzo; Kasayama, Soji

    2017-01-01

    Glycated albumin (GA) reflects shorter-term glycemic control than HbA1c. We have reported that HbA1c is paradoxically increased in diabetic patients whose glycemic control deteriorated before ameliorating. In this study, we analyzed paradoxical increases of glycemic control indicators after treatment in patients with fulminant type 1 diabetes (FT1D). We also investigated whether the GA/HbA1c ratio may reflect shorter-term glycemic control than GA. Five FT1D patients whose post-treatment HbA1c and GA levels were measured were enrolled. We also used a formula to estimate HbA1c and GA from the fictitious models of changes in plasma glucose in FT1D patients. In this model, the periods during which HbA1c, GA, and the GA/HbA1c ratio were higher than at the first visit were compared. In addition, the half-life for the GA/HbA1c ratio was calculated in accordance with the half-lives for HbA1c and GA (36 and 14 days, respectively). In all FT1D patients, HbA1c levels 2-4 weeks after treatment were increased, with three patients (60%) experiencing an increase of GA levels. In contrast, an increase of the GA/HbA1c ratio was observed in only one patient. In all of the different models of changes in plasma glucose in FT1D patients, the length of time during which the values were higher than at the first visit was in the order of HbA1c > GA > GA/HbA1c ratio. The half-life for the GA/HbA1c ratio was 9 days, shorter than GA. These findings suggest that the GA/HbA1c ratio reflects shorter-term glycemic control than GA. © 2016 Wiley Periodicals, Inc.

  14. Primary and booster vaccination with DTPw-HB/Hib pentavalent vaccine in Costa Rican children who had received a birth dose of hepatitis B vaccine Vacunación primaria y de refuerzo con la vacuna pentavalente DTPw-HB/Hib en niños costarricenses vacunados al nacer contra la hepatitis B

    Directory of Open Access Journals (Sweden)

    Idis Faingezicht

    2002-10-01

    Full Text Available Objective. The DTPw-HB/Hib pentavalent combination vaccine has been developed following recommendations of the World Health Organization for the introduction of hepatitis B (HB and Haemophilus influenzae type b (Hib vaccines into routine childhood vaccination programs. The objectives of this study were to: 1 analyze the immunogenicity and the reactogenicity of the DTPw-HB/Hib pentavalent combination vaccine in comparison to separate injections of DTPw-HB and Hib vaccines as primary vaccination in a group of children who had received a dose of HB vaccine at birth and 2 in the second year of life to assess the antibody persistence as well as the response to a DTPw-HB/Hib or DTPw/Hib booster. Methods. In the first part of the study (primary-vaccination stage, conducted in 1998-1999, we analyzed the immunogenicity and reactogenicity of the DTPw-HB/Hib combination vaccine in comparison to separate injections of DTPw-HB and Hib vaccines as primary vaccination at 2, 4, and 6 months of age in 207 Costa Rican children who had received a dose of HB vaccine at birth. Later, in the booster-vaccination stage of the study, in 1999-2000, in a subset of the children (69 toddlers, now 15-18 months old, antibody persistence was measured, and response to a DTPw-HB/Hib or DTPw/Hib booster was also assessed. Results. In both primary-vaccination groups, at least 97.5% of the infants reached protective levels of antibodies (seropositivity against the antigens employed in the vaccines. The DTPw-HB/Hib pentavalent combination vaccine did not result in more local reactions than did the DTPw-HB vaccine alone, and, in terms of general reactions, there was no clinically significant difference between the combination or separate injections, and with the pentavalent vaccine having the benefit of needing one less injection. Nine months after the third dose of the primary-vaccination course, antibody persistence was similar in both groups, with over 93% of children still having

  15. Genetic Variants at BCL11A and HBS1L-MYB loci Influence Hb F Levels in Chinese Zhuang β-Thalassemia Intermedia Patients.

    Science.gov (United States)

    Lai, Yunli; Chen, Yun; Chen, Biyan; Zheng, Haiyang; Yi, Sheng; Li, Guojian; Wei, Hongwei; He, Sheng; Zheng, Chenguang

    2016-11-01

    Increased Hb F levels can ameliorate the symptoms of β-thalassemia (β-thal). Due to the genetic heterogenicity of β-thal, the relationship between genetic variants in modifier genes and Hb F level has been studied in different populations. The Chinese Zhuang has the second largest population in China and has 6.78% prevalence of β-thal. However, the effects of these single nucleotide polymorphism (SNP) variants on the Hb F levels of β-thal intermedia (β-TI) patients in this population have not been reported. To explore the association between modifier loci (β-globin gene cluster, HBS1L-MYB intergenic region and BCL11A) and Hb F levels in Chinese Zhuang β-TI patients, 96 unrelated β-TI patients (50 males and 46 females) with different Hb F levels were recruited and genotyped by mass spectrometry. A total of 13 SNPs were confirmed to be in a significant relationship with Hb F levels in this population. Of these, high-risk genotypes of six Hb F-associated SNPs, rs9376090, rs7776054, rs9399137, rs9389268, rs9402685 in the HBS1L-MYB intergenic region and rs189984760 in the BCL11A locus, showed association with high Hb F levels, especially for SNPs in linkage disequilibrium. One novel Hb F-associated SNP, rs189984760, was identified in our study. Our findings will be of valuable reference for correlation between modifier genes and Hb F in Chinese Zhuang populations and may lead to better understand the modifying mechanisms for β-thal.

  16. Knowledge and Outcome Measure of HbA1c Testing in Asian Indian Patients with Type 2 Diabetes from a Tertiary Care Center

    Science.gov (United States)

    Kumpatla, Satyavani; Medempudi, Srikanth; Manoharan, Deepa; Viswanathan, Vijay

    2010-01-01

    Aim: HbA1c test is considered to be the reliable measure for evaluating long-term glycemic control in type 2 diabetes. The purpose of this study was to evaluate whether knowledge about HbA1c test is associated with a better glycemic control. Materials and Methods: We conducted a cross-sectional survey of 480 (M:F; 287:193) adults with type 2 diabetes attending a tertiary care center during a period of four months. Baseline demographic and clinical data of all the subjects was obtained. Subject’s knowledge about HbA1c test and their target goal was assessed using a questionnaire. Recent HbA1c results were obtained from medical records. Results: Seventy four per cent of the subjects had awareness about HbA1c test and about 43% of those who knew HbA1c test also knew their target goal. 33% remember their last HbA1c result. The mean A1C of Group A was significantly lower when compared with Group B (8.1 ± 1.7 vs 9.2 ± 1.9, P<0.0001). Group C had lower A1C levels compared to Group D (7.7 ± 1.4 vs 8.5 ± 1.9, p<0.0001). Patients who kept their HbA1c less than 7% were significantly higher in Group C than in Group D. (37.8 vs 12.7%, p<0.00001). Subjects had good glycemic control with increasing levels of awareness about HbA1c. Conclusion: Majority of the diabetic patients who attended the tertiary care center for diabetes care knew HbA1c test and half of them were aware about their target goal. Awareness about HbA1c had a positive impact on maintenance of better glycemic control. PMID:20922109

  17. Heparin-Binding EGF-like Growth Factor (HB-EGF) stimulates the proliferation of Müller glia-derived progenitor cells in avian and murine retinas

    Science.gov (United States)

    Todd, Levi; Volkov, Leo I.; Zelinka, Chris; Squires, Natalie; Fischer, Andy J.

    2015-01-01

    Müller glia can be stimulated to de-differentiate, proliferate and form Müller glia-derived progenitor cells (MGPCs) that regenerate retinal neurons. In the zebrafish retina, Heparin-Binding EGF-like Growth Factor (HB-EGF) may be one of the key factors that stimulate the formation of proliferating MGPCs. Currently nothing is known about the influence of HB-EGF on the proliferative potential of Müller glia in retinas of birds and rodents. In the chick retina, we found that levels of both hb-egf and egf-receptor are rapidly and transiently up-regulated following NMDA-induced damage. Although intraocular injections of HB-EGF failed to stimulate cell-signaling or proliferation of Müller glia in normal retinas, HB-EGF stimulated proliferation of MGPCs in damaged retinas. By comparison, inhibition of the EGF-receptor (EGFR) decreased the proliferation of MGPCs in damaged retinas. HB-EGF failed to act synergistically with FGF2 to stimulate the formation of MGPCs in the undamaged retina and inhibition of EGF-receptor did not suppress FGF2-mediated formation of MGPCs. In the mouse retina, HB-EGF stimulated the proliferation of Müller glia following NMDA-induced damage. Furthermore, HB-EGF stimulated not only MAPK-signaling in Müller glia/MGPCs, but also activated mTor- and Jak/Stat-signaling. We propose that levels of expression of EGFR are rate-limiting to the responses of Müller glia to HB-EGF and the expression of EGFR can be induced by retinal damage, but not by FGF2-treatment. We conclude that HB-EGF is mitogenic to Müller glia in both chick and mouse retinas, and HB-EGF is an important player in the formation of MGPCs in damaged retinas. PMID:26500021

  18. Risk assessment and HbA1c measurement in Norwegian community pharmacies to identify people with undiagnosed type 2 diabetes - A feasibility study.

    Science.gov (United States)

    Risøy, Aslaug Johanne; Kjome, Reidun Lisbet Skeide; Sandberg, Sverre; Sølvik, Una Ørvim

    2018-01-01

    Determine the feasibility of using a diabetes risk assessment tool followed by HbA1c-measurement in a community-pharmacy setting in Norway. In this longitudinal study two pharmacists in each of three community pharmacies were trained to perform risk assessments, HbA1c-measurements and counselling. Pharmacy customers who were > 18 years old and could understand and speak Norwegian or English were recruited in the pharmacies during a two-months-period. Information about the service was presented in local newspapers, social media, leaflets and posters at the pharmacy. Customers wishing to participate contacted the pharmacy staff. Participants completed a validated diabetes risk test and a background questionnaire including a validated instrument for self-rated health. A HbA1c measurement was performed for individuals with a moderate to high risk of developing diabetes. If HbA1c ≥ 6.5% they were recommended to visit their general practitioner for follow-up. The pharmacies performed internal and external quality control of the HbA1c instrument. Of the 211 included participants 97 (46%) were > 50 years old. HbA1c was measured for the 47 participants (22%) with high risk. Thirty-two (15%) had HbA1c values HbA1c ≥ 6.5%. Two participants with HbA1 ≥ 6.5% were diagnosed with diabetes by their general practitioner. The third was lost to follow-up. Results from internal and external quality control for HbA1c were within set limits. The pharmacists were able to perform the risk assessment and measurement of HbA1c, and pharmacy customers were willing to participate. The HbA1c measurements fulfilled the requirements for analytical quality. Thus, it is feasible to implement this service in community pharmacies in Norway. In a large-scale study the inclusion criteria should be increased to 45 years in accordance with the population the risk test has been validated for.

  19. 76 FR 21401 - Notice of Availability of the Draft EIS for the HB In-Situ Solution Mine Project, Eddy County, NM

    Science.gov (United States)

    2011-04-15

    ...] Notice of Availability of the Draft EIS for the HB In-Situ Solution Mine Project, Eddy County, NM AGENCY... prepared a Draft Environmental Impact Statement (EIS) for the HB In- Situ Solution Mine Project, and by... considered, the BLM must receive written comments on the HB In-Situ Solution Mine Project Draft EIS within 60...

  20. Modifying effects of maternal Hb concentration on infant birth weight in women receiving prenatal iron-containing supplements: a randomised controlled trial.

    Science.gov (United States)

    Wang, Linlin; Mei, Zuguo; Li, Hongtian; Zhang, Yali; Liu, Jianmeng; Serdula, Mary K

    2016-02-28

    Concerns have been raised about the benefits of Fe-containing supplements on infant birth weight among women with normal/high Hb levels at baseline. Thus far, no clinical trials have examined whether the effects of prenatal Fe-containing supplements on birth weight vary by maternal Hb levels. We compared the effects of Fe-folic acid (IFA) or multiple micronutrients (MMN) with folic acid (FA) supplements on birth weight among pregnant women with mild/no anaemia or high Hb levels. A double-blind randomised controlled trial was conducted in 2006-2009. In total, 18 775 pregnant women with mild/no anaemia (145 g/l) baseline Hb levels, IFA and MMN supplements increased birth weight by 91·44 (95% CI 3·37, 179·51) g and 107·63 (95% CI 21·98, 193·28) g (PHb concentration. In conclusion, the effects of Fe-containing supplements on birth weight depended on baseline Hb concentrations. The Fe-containing supplements improved birth weight in women with very high Hb levels before 20 weeks of gestation.

  1. Atividade da 6-fosfogliconato desidrogenase em deficientes de glicose-6-fosfato desidrogenase Activity of 6-phosphogluconate dehydrogenase in glucose-6-phosphate dehydrogenase deficiency

    Directory of Open Access Journals (Sweden)

    Daniela B. Nicolielo

    2006-06-01

    Full Text Available As enzimas G6PD e 6PGD são responsáveis pela geração do aporte de NADPH, necessário para a detoxificação dos agentes oxidantes produzidos pelo estresse oxidativo metabólico nos eritrócitos. Devido à alta prevalência de deficiência de G6PD na população mundial, principalmente de origem negróide africana, muitos estudos têm sido realizados na tentativa de conhecer melhor a atuação destas enzimas. O objetivo deste estudo foi avaliar a atividade enzimática da 6PGD, nos deficientes de G6PD, para verificar a existência de aumento da atividade desta enzima, correlacionando com um possível aumento do número de reticulócitos ou presença de alterações da série vermelha. A pesquisa em 2.657 indivíduos do sexo masculino resultou em 97 deficientes de G6PD, determinando uma prevalência de 3,65% para a região de Bauru (SP, com atividade enzimática média de G6PD de 1,74 UI.g Hb-1. min-1 a 37ºC, 14,4% da atividade da G6PD normal. A atividade enzimática média da 6PGD foi de 9,5 UI.g Hb-1. min-1 a 37ºC, estando aumentada em 47,4% dos deficientes de G6PD. Os resultados não confirmaram que a hipótese do aumento da atividade enzimática da 6PGD, em deficientes de G6PD, seja decorrente da presença de um número aumentado de reticulócitos na corrente circulatória, faixa etária ou alterações eritrocitométricas que denotem anemia. O mais provável é que a hemólise autolimitada, imposta pelos processos oxidativos, preserve os eritrócitos mais jovens, que possuem atividade enzimática mais elevada, uma vez que naturalmente ocorre diminuição da atividade destas enzimas com o envelhecimento celular.The G6PD and 6PGD enzymes are responsible for the generation of NADPH supply necessary for the detoxification of the oxidant agents produced during the oxidative metabolic stress on erythrocytes. Due to the high prevalence of the deficiency of G6PD on world population, especially on Afro descents, many studies have been done trying

  2. Physical activity and change in fasting glucose and HbA1c: a quantitative meta-analysis of randomized trials.

    Science.gov (United States)

    Boniol, Mathieu; Dragomir, Miruna; Autier, Philippe; Boyle, Peter

    2017-11-01

    A systematic review was conducted of randomized trials which evaluated the impact of physical activity on the change in fasting glucose and HbA1c. A literature search was conducted in PubMed until December 2015. Studies reporting glucose or HbA1c at baseline and at the end of study were included, and the change and its variance were estimated from studies with complete data. Mixed-effect random models were used to estimate the change of fasting glucose (mg/dl) and HbA1c (%) per additional minutes of physical activity per week. A total of 125 studies were included in the meta-analysis. Based on 105 studies, an increase of 100 min in physical activity per week was associated with an average change of -2.75 mg/dl of fasting glucose (95% CI -3.96; -1.55), although there was a high degree of heterogeneity (83.5%). When restricting the analysis on type 2 diabetes and prediabetes subjects (56 studies), the average change in fasting glucose was -4.71 mg/dl (95% CI -7.42; -2.01). For HbA1c, among 76 studies included, an increase of 100 min in physical activity per week was associated with an average change of -0.14% of HbA1c (95% CI -0.18; -0.09) with heterogeneity (73%). A large degree of publication bias was identified (Egger test p HbA1c was -0.16% (95% CI -0.21; -0.11). This analysis demonstrates that moderate increases in physical activity are associated with significant reductions in both fasting glucose and HbA1c.

  3. Folate-conjugated polymeric micelle HB-loaded on targeting effect by intraperitoneal to ovarian cancer in vitro and in vivo.

    Science.gov (United States)

    Li, Jie; Yao, Shu; Wang, Kai; Lu, Zaijun; Su, Xuantao; Li, Li; Yuan, Cunzhong; Feng, Jinbo; Yan, Shi; Kong, Beihua; Song, Kun

    2018-04-04

    Photodynamic therapy (PDT) is considered as an innovative and attractive modality to treat ovarian cancer. In this study, a biodegradable polymer poly (ethylene glycol)-poly (lactic acid)(PLA)-folate (FA-PEG-PLA) was prepared in order to synthesize an active targeting, water soluble and pharmacomodulated photosensitizer nano-carriers. The drug loading content, encapsulation efficiency, in vitro and in vivo release were characterized, in which HB/FA-PEG-PLA micelles had a high encapsulation efficiency and much slower control release for drugs compared to free drugs (pHB/FA-PEG-PLA micelles, the cellular uptake study in vitro were tested, which owned significantly enhanced uptake of HB/FA-PEG-PLA micelles in SKOV3 (FR+) compared to A2780 cancer cells (FR-). The enhanced uptake of HB/FA-PEG-PLA micelles to cancer cells resulted in a more effective post-PDT killing of SKOV3 cells compared to plain micelles and free drugs. Binding and uptake of HB/FA-PEG-PLA micelles by SKOV3 cells were also observed in vivo after intraperitoneal injection of folate targeted micelles in tumor-bearing ascitic ovarian cancer animals. The drug levels in ascitic tumor tissues were increased by 20-fold (pHB-loaded micelles were mainly distributed in kidney and liver (the main clearance organs) in biodistribution. These results demonstrated that our new developed PDT photosensitizer HB/FA-PEG-PLA micelles has a high drug-loading capacity, good biocompatibility, control drug release, and enhanced targeting and antitumor effect, which is a potential approach to future targeting ovarian cancer therapy. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  4. Single-Use Disposable Electrochemical Label-Free Immunosensor for Detection of Glycated Hemoglobin (HbA1c Using Differential Pulse Voltammetry (DPV

    Directory of Open Access Journals (Sweden)

    Alireza Molazemhosseini

    2016-07-01

    Full Text Available A single-use disposable in vitro electrochemical immunosensor for the detection of HbA1c in undiluted human serum using differential pulse voltammetry (DPV was developed. A three-electrode configuration electrochemical biosensor consisted of 10-nm-thin gold film working and counter electrodes and a thick-film printed Ag/AgCl reference electrode was fabricated on a polyethylene terephthalate (PET substrate. Micro-fabrication techniques including sputtering vapor deposition and thick-film printing were used to fabricate the biosensor. This was a roll-to-roll cost-effective manufacturing process making the single-use disposable in vitro HbA1c biosensor a reality. Self-assembled monolayers of 3-Mercaptopropionic acid (MPA were employed to covalently immobilize anti-HbA1c on the surface of gold electrodes. Electrochemical impedance spectroscopy (EIS and X-ray photoelectron spectroscopy (XPS confirmed the excellent coverage of MPA-SAM and the upward orientation of carboxylic groups. The hindering effect of HbA1c on the ferricyanide/ferrocyanide electron transfer reaction was exploited as the HbA1c detection mechanism. The biosensor showed a linear range of 7.5–20 µg/mL of HbA1c in 0.1 M PBS. Using undiluted human serum as the test medium, the biosensor presented an excellent linear behavior (R2 = 0.999 in the range of 0.1–0.25 mg/mL of HbA1c. The potential application of this biosensor for in vitro measurement of HbA1c for diabetic management was demonstrated.

  5. Single-Use Disposable Electrochemical Label-Free Immunosensor for Detection of Glycated Hemoglobin (HbA1c) Using Differential Pulse Voltammetry (DPV).

    Science.gov (United States)

    Molazemhosseini, Alireza; Magagnin, Luca; Vena, Pasquale; Liu, Chung-Chiun

    2016-07-01

    A single-use disposable in vitro electrochemical immunosensor for the detection of HbA1c in undiluted human serum using differential pulse voltammetry (DPV) was developed. A three-electrode configuration electrochemical biosensor consisted of 10-nm-thin gold film working and counter electrodes and a thick-film printed Ag/AgCl reference electrode was fabricated on a polyethylene terephthalate (PET) substrate. Micro-fabrication techniques including sputtering vapor deposition and thick-film printing were used to fabricate the biosensor. This was a roll-to-roll cost-effective manufacturing process making the single-use disposable in vitro HbA1c biosensor a reality. Self-assembled monolayers of 3-Mercaptopropionic acid (MPA) were employed to covalently immobilize anti-HbA1c on the surface of gold electrodes. Electrochemical impedance spectroscopy (EIS) and X-ray photoelectron spectroscopy (XPS) confirmed the excellent coverage of MPA-SAM and the upward orientation of carboxylic groups. The hindering effect of HbA1c on the ferricyanide/ferrocyanide electron transfer reaction was exploited as the HbA1c detection mechanism. The biosensor showed a linear range of 7.5-20 µg/mL of HbA1c in 0.1 M PBS. Using undiluted human serum as the test medium, the biosensor presented an excellent linear behavior (R² = 0.999) in the range of 0.1-0.25 mg/mL of HbA1c. The potential application of this biosensor for in vitro measurement of HbA1c for diabetic management was demonstrated.

  6. A novel hemoglobin variant found on the α1 chain: Hb KSVGH (HBA1: p.Lys57_Gly58insSerHisGlySerAlaGlnValLys).

    Science.gov (United States)

    Wang, Mei-Chun; Tsai, Kuo-Wang; Chu, Chih-Hsun; Yu, Ming-Sun; Lam, Hing-Chung

    2015-01-01

    Glycosylated hemoglobin (Hb A1C) is a crucial indicator for the long-term control and the diagnosis of diabetes. However, the presence of hemoglobin (Hb) variants may affect the measured value of Hb A1C and result in an abnormal graph trend and inconsistency between the clinical blood sugar test and Hb A1C values. In this study, laboratory data of 41,267 patients with diabetes were collected. The Hb A1C levels and the graph results were examined. We identified 74 cases containing abnormal Hb A1C graph trends. The conducted blood cell counts and capillary Hb electrophoresis were used to analyze Hb variants. We also determined gene variation for the Hb variants by a sequence approach. Fifteen different types of Hb variants were identified in this study. Among these, we found a novel variant in which the α1 subunit of Hb showed an insertion of 24 nucleotides (nts) between the 56th and 57th residues. We named this novel variant Hb Kaohsiung Veterans General Hospital (Hb KSVGH) (HBA1: p.Lys57_Gly58insSerHisGlySerAlaGlnValLys).

  7. Factors associated with reaching or not reaching target HbA1c after initiation of basal or premixed insulin in patients with type 2 diabetes.

    Science.gov (United States)

    Scheen, A J; Schmitt, H; Jiang, H H; Ivanyi, T

    2017-02-01

    To evaluate factors associated with reaching or not reaching target glycated haemoglobin (HbA 1c ) levels by analysing the respective contributions of fasting hyperglycaemia (FHG), also referred to as basal hyperglycaemia, vs postprandial hyperglycaemia (PHG) before and after initiation of a basal or premixed insulin regimen in patients with type 2 diabetes. This post-hoc analysis of insulin-naïve patients in the DURABLE study randomised to receive either insulin glargine or insulin lispro mix 25 evaluated the percentages of patients achieving a target HbA 1c of <7.0% (<53mmol/mol) per baseline HbA 1c quartiles, and the effect of each insulin regimen on the relative contributions of PHG and FHG to overall hyperglycaemia. Patients had comparable demographic characteristics and similar HbA 1c and FHG values at baseline in each HbA 1c quartile regardless of whether they reached the target HbA 1c . The higher the HbA 1c quartile, the greater was the decrease in HbA 1c , but also the smaller the percentage of patients achieving the target HbA 1c . HbA 1c and FHG decreased more in patients reaching the target, resulting in significantly lower values at endpoint in all baseline HbA 1c quartiles with either insulin treatment. Patients not achieving the target HbA 1c had slightly higher insulin doses, but lower total hypoglycaemia rates. Smaller decreases in FHG were associated with not reaching the target HbA 1c , suggesting a need to increase basal or premixed insulin doses to achieve targeted fasting plasma glucose and improve patient response before introducing more intensive prandial insulin regimens. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  8. Regional variations in frequency of glycosylated hemoglobin (HbA1c) monitoring in Korea: A multilevel analysis of nationwide data.

    Science.gov (United States)

    Yoo, Kyoung-Hun; Shin, Dong-Wook; Cho, Mi-Hee; Kim, Sang-Hyuck; Bahk, Hyun-Jung; Kim, Shin-Hye; Jeong, Su-Min; Yun, Jae-Moon; Park, Jin-Ho; Kim, Heesun; Cho, BeLong

    2017-09-01

    Suboptimal frequency of glycosylated hemoglobin (HbA1c) monitoring is associated with poor diabetes control. We aimed to analyze compliance to HbA1c testing guidelines and explore associated individual and area-level determinants, focusing on regional variation. This cross-sectional study between the period of 2012-2013 was conducted by using the Korean National Health Insurance Research Database, and included 45,634 patients diagnosed with diabetes mellitus, who were prescribed any anti-diabetic medications, including insulin. We calculated the proportion of each HbA1c testing frequency (≥1, ≥2, or ≥4 times per year) stratified by 17 administrative regions. Multilevel and multivariate logistic analyses were performed with regional (proportion of farmer population) and individual characteristics (age, sex, income level, duration of diabetes, and most visited medical institution). Overall, 67.3% of the patients received≥1 HbA1c test per year; 37.8% and 6.1% received ≥2 and ≥4 tests per year, respectively. Those managed in secondary-level hospitals or clinics and those living in rural areas were less likely to receive HbA1c testing. Even after adjusting for individual and regional level characteristics, significant area level variation was observed (variance participant coefficients were 7.91%, 9.58%, and 14.43% for testing frequencies of ≥1, ≥2, and ≥4 times a year, respectively). The frequency of HbA1c monitoring is suboptimal in Korea, especially in rural areas. Moreover, significant regional variation was observed, implying a contextual effect. This suggests the need for developing policy actions to improve HbA1c monitoring. In particular, access to HbA1c testing in rural primary care clinics must be improved. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. The impact of ambient temperature on HbA1c in Taiwanese type 2 diabetic patients: The most vulnerable subgroup.

    Science.gov (United States)

    Tien, Kai-Jen; Yang, Chwen-Yi; Weng, Shih-Feng; Liu, Su-Yen; Hsieh, Ming-Chia; Chou, Chien-Wen

    2016-05-01

    The relationship between temperature variability and HbA1c has been reported in Caucasians, but not for Asians of Taiwanese origin. This study investigated the impact of temperature on HbA1c in various groups of Taiwanese with type 2 diabetes in Taiwan. For this longitudinal follow-up study which started in 2006, we recruited a total of 4399 patients with type 2 diabetes who had been regularly followed up at Chi Mei Medical Center and obtained local temperature data for 2006 to 2011 from Taiwan's Central Weather Bureau. We used a generalized estimated equation (GEE) to analyze the HbA1c level and its change over time with temperature and temperature changes, respectively. We found a negative correlation between HbA1c and temperature (R = -0.475, p = 0.001). For every 1°C decrement in temperature, there was an increase in the risk of having a HbA1c level >7% [p HbA1c > 7% among those in the lowest quartile of temperatures than the highest quartile (p = 0.0038, adjusted OR: 1.13). Patients with diabetic patients were at higher risk of HbA1C > 7% in the winter and spring than those in the summer (adjusted OR: 1.13, p = 0.0027; adjusted OR: 1.14, p = 0.0022). After adjusting for various confounders, we found people who were younger than 65 years old, people who had diabetes for longer than 6 years, and people who had a body mass index (BMI) HbA1c levels in Taiwanese people with type 2 diabetes, especially in people under 65 years old, people with diabetes for longer than 6 years, and those with a BMI < 24. Copyright © 2015. Published by Elsevier B.V.

  10. Prenatal control of Hb Bart's disease in mainland China: can we do better?

    Science.gov (United States)

    He, Ping; Yang, Yu; Li, Ru; Li, Dong-Zhi

    2014-01-01

    The aim of the present study was to report a 3-year experience on the prenatal control of Hb Bart's (γ4) disease in Mainland China. All pregnancies with fetal Hb Bart's disease were included from January 2011 to December 2013. The main clinical characteristics of the affected pregnancies were reviewed, including maternal reproductive history, prenatal care in the current pregnancy, the gestation of pregnancy at the time of booking, the gestation at the time of prenatal diagnosis (PND), and the complications associated with the pregnancy. A total of 246 cases of fetal Hb Bart's disease were identified during the study period; among these, 177 (72.0%) were diagnosed in early gestation (≤24 weeks), and 69 (28.0%) in late gestation. Most (87.0%) of the patients presenting in late pregnancy had late or no prenatal care. Twenty (29.0%) had major obstetrical complications in patients presenting in late pregnancy, and five (5.0%) in patients presenting in relatively early pregnancy. The delay in PND deprived couples of opportunities to make informed decisions early in pregnancy. Efforts for designing and targeting strategies to improve the timeliness of prenatal care are urgently needed.

  11. HbA1c Levels among Primary Healthcare Patients with Type 2 Diabetes Mellitus in Oman

    Directory of Open Access Journals (Sweden)

    Jawad A Al-Lawati

    2012-11-01

    Full Text Available Objectives: To investigate whether younger patients with type 2 diabetes mellitus have higher glycated hemoglobin A1c (HbA1c levels compared to older patients, and to determine the factors associated with higher HbA1c levels.Methods: Data from 1,266 patients from all over Oman were used to obtain the mean HbA1c level, odds ratios (OR, and 95% confidence intervals (CI from multiple logistic regression models with age groups, sex, duration of diabetes, diabetes treatment, body mass index, estimated glomerular filtration rate (eGFR, tobacco use, and healthcare index as predictors of good (HbA1c <7% vs.poor (≥7% glycemic control.Results: Mean HbA1c levels were 8.9, 8.3, and 7.8 in the age groups 20-39, 40-59 and 60+ years, respectively. After controlling for all other covariates, the OR of good glycemic control increased with age, 40-59 years old (OR=1.7; 95% CI 1.1 to 2.6 and 60+ year (OR=2.5; 95% CI 1.6 to 4.0, female gender (OR=1.5; 95% CI 1.2 to 2.0 and in patients with eGFR ≥60 mL/min/1.73 m2 (OR=1.9; 95% CI 1.1 to 3.3. Longer duration of diabetes (≥5years and treatment with oral agents or insulin were inversely related to good glycemic control.Conclusion: Younger Omani adults exhibit worse glycemic levels compared to older adults posing a formidable challenge to diabetes care teams.

  12. A1c Gear: Laboratory quality HbA1c measurement at the point of care.

    Science.gov (United States)

    Ejilemele, Adetoun; Unabia, Jamie; Ju, Hyunsu; Petersen, John R

    2015-05-20

    HbA1c is an important part of assessing the diabetic control and since the use of point-of-care devices for monitoring HbA1c is increasing, it is important to determine how these devices compare to the central laboratory. One hundred and twenty patient samples were analyzed on the Bio-Rad Variant™II and one POC analyzer (Sakae A1c Gear). Three patient sample pools containing ~5%, ~7%, and ~10% HbA1c levels were run over 20 days. Three reagent lots and three instruments were evaluated for the A1c Gear. The 120 patient samples showed strong correlation (R(2)>0.989) when compared to the Variant™II with means=8.06% and 7.81%, for Variant IIand A1c Gear, respectively. Changing reagent lots or instruments had no impact for the A1c Gear. The ~5%, ~7%, and ~10% pools within-run and between-run imprecision was between 0.87-1.33% and 1.03-1.32%, and 1.41-2.35% and 1.24-1.89% with total imprecision of 1.67-2.35% and 1.61-2.31% for the A1c Gear and Variant II, respectively. The A1c Gear showed a small negative bias (0.25% HbA1c) across HbA1c measurement ranges of Gear meets the criteria of total CV Gear can give results as precise as the laboratory at the POC. Copyright © 2015. Published by Elsevier B.V.

  13. The change points of HbA(1C) for detection of retinopathy in Chinese type 2 diabetic patients.

    Science.gov (United States)

    Hou, Jia-Ning; Bi, Yu-Fang; Xu, Min; Huang, Yun; Li, Xiao-Ying; Wang, Wei-Qing; Chen, Yu-Hong; Ning, Guang

    2011-03-01

    To investigate the change points of HbA(1C) for detection of retinopathy in Chinese type 2 diabetic patients. This cross-sectional investigation included 992 diagnosed type 2 diabetic patients, who received non-mydriatic digital fundus photography examination. Joinpoint regression software was adopted to identify the change points of HbA(1C) in association with retinopathy prevalence. The mean age of all patients was 59.1 ± 8.4 years and the duration of diabetes was 5.5 (95% CI: 5.2-5.9) years. The prevalence of retinopathy was 10.3% in total, and 4.1%, 7.4% and 19.6% in patients with different diabetes duration of ≤ 5 years, 5-10 years and >10 years, respectively. The change point of HbA(1C) was 6.5% (95%CI 5.8-7.5%), at which retinopathy prevalence began to rise sharply. Furthermore, in subjects with diabetes duration ≤ 5 years, 5-10 years and >10 years, the change points of HbA(1C) were 8.1% (95%CI 7.9-8.3%), 6.1% (95%CI 5.7-6.8%), 5.6% (95%CI 5.1-8.1%) for detection of retinopathy, respectively. The steepest increase in retinopathy prevalence occurred when HbA(1C) reached 6.5%. However, the duration of diabetes should be taken into concern, when using the change points of HbA(1C) for detection of retinopathy in diabetic patients. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  14. Perfil hematimétrico e identificação da hemoglobina do bicho preguiça Bradypus variegatus

    OpenAIRE

    Ferrari Ramos, Francimar

    2006-01-01

    O objetivo deste estudo foi, em preguiças Bradypus variegatus, estabelecer o perfil hematimétrico e identificar os tipos de hemoglobina (Hb), além de avaliar se existe influência do sexo sobre estes parâmetros. Estudou-se 10 preguiças (6 machos e 4 fêmeas), não anestesiadas, mantidas em cativeiro, pesando (X±DP) 3,6±0,79kg e com temperatura retal média de 30±1oC. Coleta de sangue, através de punção da veia cefálica medial do membro anterior, foi obtida para realização da hematimetria, do esfr...

  15. A new gene deletion in the alpha-like globin gene cluster as the molecular basis for the rare alpha-thalassemia-1(--/alpha alpha) in blacks: HbH disease in sickle cell trait.

    Science.gov (United States)

    Steinberg, M H; Coleman, M B; Adams, J G; Hartmann, R C; Saba, H; Anagnou, N P

    1986-02-01

    A novel deletion of at least 26 kilobase of DNA, including both alpha-globin genes, the psi alpha- and psi zeta-globin genes, but sparing the functional zeta-gene was found in a 10-year-old black boy with HbH disease and sickle cell trait. This particular deletion has not previously been described in blacks. Its existence makes it likely that the absence of Hb Barts hydrops fetalis in blacks is due to the rarity of the chromosome lacking two alpha-globin genes rather than a result of early embryonic death due to the failure to synthesize embryonic hemoglobins because of deletion of functional zeta-globin genes.

  16. Primary and booster vaccination with DTPw-HB/Hib pentavalent vaccine in Costa Rican children who had received a birth dose of hepatitis B vaccine

    Directory of Open Access Journals (Sweden)

    Idis Faingezicht

    2002-10-01

    Full Text Available Objective. The DTPw-HB/Hib pentavalent combination vaccine has been developed following recommendations of the World Health Organization for the introduction of hepatitis B (HB and Haemophilus influenzae type b (Hib vaccines into routine childhood vaccination programs. The objectives of this study were to: 1 analyze the immunogenicity and the reactogenicity of the DTPw-HB/Hib pentavalent combination vaccine in comparison to separate injections of DTPw-HB and Hib vaccines as primary vaccination in a group of children who had received a dose of HB vaccine at birth and 2 in the second year of life to assess the antibody persistence as well as the response to a DTPw-HB/Hib or DTPw/Hib booster. Methods. In the first part of the study (primary-vaccination stage, conducted in 1998-1999, we analyzed the immunogenicity and reactogenicity of the DTPw-HB/Hib combination vaccine in comparison to separate injections of DTPw-HB and Hib vaccines as primary vaccination at 2, 4, and 6 months of age in 207 Costa Rican children who had received a dose of HB vaccine at birth. Later, in the booster-vaccination stage of the study, in 1999-2000, in a subset of the children (69 toddlers, now 15-18 months old, antibody persistence was measured, and response to a DTPw-HB/Hib or DTPw/Hib booster was also assessed. Results. In both primary-vaccination groups, at least 97.5% of the infants reached protective levels of antibodies (seropositivity against the antigens employed in the vaccines. The DTPw-HB/Hib pentavalent combination vaccine did not result in more local reactions than did the DTPw-HB vaccine alone, and, in terms of general reactions, there was no clinically significant difference between the combination or separate injections, and with the pentavalent vaccine having the benefit of needing one less injection. Nine months after the third dose of the primary-vaccination course, antibody persistence was similar in both groups, with over 93% of children still having

  17. Lacking deoxygenation-linked interaction between cytoplasmic domain of band 3 and HbF from fetal red blood cells

    DEFF Research Database (Denmark)

    Weber, Roy E.

    2007-01-01

    Aim: Several of the red blood cell's metabolic and membrane functions display dependence on haemoglobin oxygenation. In adult human red cells, the increased glycolytic rate at low O2 tension results from binding of deoxygenated HbA at negatively charged, N-terminal, cytoplasmic domain of the memb......Aim: Several of the red blood cell's metabolic and membrane functions display dependence on haemoglobin oxygenation. In adult human red cells, the increased glycolytic rate at low O2 tension results from binding of deoxygenated HbA at negatively charged, N-terminal, cytoplasmic domain...... of the membrane protein band 3, which liberates glycolytic enzymes from this site. This study aims to investigate the role of fetal HbF (that has lower anion-binding capacity than HbA) in fetal red cells (that are subjected to low O2 tensions), and to elucidate possible linkage (e.g. via the major red cell...... membrane organising centre, band 3) between the individual oxygenation-linked reactions encountered in red cells. Methods: The interaction between band 3 and Hb is analysed in terms of the effects, measured under different conditions, of a 10-mer peptide that corresponds to the N-terminus of human band 3...

  18. Hb I-Toulouse in association with homozygosity for the α3.7 deletion in a Pacific Island woman

    Directory of Open Access Journals (Sweden)

    Beverley Pullon

    2016-11-01

    Full Text Available Only four cases of Hb I-Toulouse have been reported to date. Current literature associates Hb I-Toulouse in the heterozygote with a mild chronic hemolytic anemia. The variant is mildly unstable with a tendency to form metHb. The quantity of the variant in heterozygotes has been reported as varying between 33 to 40%. This report confirms the finding from a single case, that a reduced percentage of Hb IToulouse along with microcytosis can be attributed to the co-inheritance of an abnormal α globin genotype. This current case was found in a woman of Pacific People ethnicity residing in New Zealand. There is a high prevalence of α thalassemia in this ethnic group and New Zealand has the highest Pacific population in the world. Therefore, if a reduced percentage of Hb I-Toulouse is found with microcytosis and normal iron studies, co-inheritance with α thalassemia should be considered. 目前仅有四例Hb I-Toulouse的病例报告。 当前的文献将杂合子中的Hb I-Toulouse与慢性溶血性贫血相关联。 这种变异体轻度不稳定,有形成高铁血红蛋白(metHb)的倾向。 杂合子中变异体数量据报道为33%至40%不等。 本报告证实从单一病例得到的结果,即伴有小红细胞症的更低Hb I-Toulouse百分比可被归结为异常α球蛋白基因型的合并遗传。 该例当前病例在一名居住在新西兰的太平洋诸岛族裔女性身上发现。 在这个族群中存在较高的α地中海贫血患病率,而在全世界新西兰的太平洋诸岛族裔人口最多。 因此,如果发现Hb I-Toulouse的百分比更低,同时伴有小红细胞症并且检查铁含量正常,则应考虑α地中海贫血的合并遗传。

  19. Problemas na padronização da reação em cadeia da polimerase para diagnóstico da tuberculose pulmonar

    Directory of Open Access Journals (Sweden)

    Bollela Valdes R.

    1999-01-01

    Full Text Available OBJETIVO: Padronizar reação em cadeia da polimerase para diagnóstico de tuberculose pulmonar, comparando os resultados obtidos com as técnicas microbiológicas clássicas, e analisar seu uso numa região de alta prevalência da tuberculose. MÉTODOS: Foram descontaminadas, após a baciloscopia, 42 amostras de escarro de pacientes. Em seguida, procedeu-se ao cultivo em Lowenstein-Jensen e à reação em cadeia da polimerase com "primers" que amplificam um fragmento de 123 pares de base do genoma do Mycobacterium tuberculosis. RESULTADOS: Das 42 amostras de escarro, 10 apresentaram cultura positiva para M. tuberculosis. Dez foram positivas à baciloscopia e 16 mostraram-se positivas na reação em cadeia da polimerase. A sensibilidade e especificidade do teste em relação à cultura foi de 90% e 81%, respectivamente. CONCLUSÕES: A reação em cadeia da polimerase tem sensibilidade comparável à da cultura e pode ser realizada em apenas um dia, resultando em tratamento precoce e melhor controle da doença. A padronização e avaliação de técnicas de biologia molecular no diagnóstico da tuberculose no Brasil é imprescindível na discussão da implantação deste exame na rotina diagnóstica em centros de referência.

  20. Prevalence of high HbA1c levels in Brazilian adolescents: The Study of Cardiovascular Risk in Adolescents.

    Science.gov (United States)

    de Cássia Lima Fernandes, Rita; Teló, Gabriela H; Cureau, Felipe V; Barufaldi, Laura A; Kuschnir, Maria Cristina C; Schaan, Beatriz D; Szklo, Moyses; Bloch, Katia V

    2017-03-01

    To evaluate the prevalence of elevated glycated haemoglobin (HbA1c) levels in a population of adolescents participating in the Study of Cardiovascular Risk in Adolescents. This is a school-based cross-sectional study based on a complex sample of adolescents 12-17years old representative at the national and macro-regional levels and for each Brazilian state capital. Blood was collected in schools and then evaluated in a single laboratory. HbA1c levels were considered elevated if ⩾5.7% (39mmol/mol) and were analyzed according to sex, age, macro-region, type of school, skin color, and nutritional status. Data from 37,804 adolescents were analyzed. The mean level of HbA1c was 5.4% (95%CI 5.4-5.4) (36mmol/mol [95%CI 36-36]), and 20.5% (95%CI 19.1-22.0) of adolescents presented values ⩾5.7% (⩾39mmol/mol). Among males, 23.6% (95%CI 21.8-25.6) showed elevated HbA1c levels compared to 17.5% (95%CI 15.9-19.2) observed in females. The prevalence of elevated levels of HbA1c was higher in adolescents with black skin color (27.6%; 95%CI 23.2-32.4) vs. white skin color (16.9%; 95%CI 15.4-18.5), and higher in those who studied in public schools (21.6%; 95%CI 20.0-23.4) vs. private schools (16.7%; 95%CI 14.7-19.0). Among obese adolescents, 29.7% (95%CI 25.4-34.3) had elevated levels of HbA1c, compared to 19.3% (95%CI 18.0-20.7) in normal weight students and 19.7% (95%CI 17.1-22.6) in overweight adolescents. Obese male adolescents of lower socioeconomic status had a higher prevalence of elevated HbA1c levels. Our findings highlight the importance of focusing on this high risk group for interventions to prevent diabetes. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Detection of Hb Rothschild HBB: c.[112T>A or 112T>C], Through High Index of Suspicion on Abnormal Pulse Oximetry.

    Science.gov (United States)

    Alli, Nazeer A; Wessels, Piet; Rampersad, Narisha; Clark, Barnaby E; Thein, Swee Lay

    2017-03-01

    We describe a case with a low oxygen affinity hemoglobin (Hb) variant who presented with cyanosis in the absence of cardiopulmonary disease. The patient, a 27-year-old pregnant female (P1G2), complained of a productive cough and bluish discoloration of the lips that started 3 days prior to seeking attention. She had no previous episodes and has generally been in good health. A positive family history of cyanosis was obtained in one sibling. Systematic examination, notably the cardiorespiratory system, revealed no abnormalities. The arterial Hb oxygen saturation (SpO 2 ) on pulse oximetry was 81.0% and Hb separation studies revealed an Hb variant identified as Hb Rothschild [β37(C3)Trp→Arg] (HBB: c.[112 T>A or 112 T>C]) by gene sequencing. The amino acid substitution (Trp→Arg) is an important contact point at the α1β2 interface and favors a T-quaternary state of the Hb tetramer. This leads to a low oxygen affinity state, which results in premature release of oxygen and drop in oxygen saturation. In the absence of cardiopulmonary disease, a decreased oxygen saturation reading, with or without cyanosis, should arouse suspicion for a possible dysHb.

  2. HbA1c as a Predictor of Diabetes and as an Outcome in the Diabetes Prevention Program: A Randomized Clinical Trial

    Science.gov (United States)

    2015-01-01

    OBJECTIVE Glycated hemoglobin (HbA1c), a standard measure of chronic glycemia for managing diabetes, has been proposed to diagnose diabetes and identify people at risk. The Diabetes Prevention Program (DPP) was a 3.2-year randomized clinical trial of preventing type 2 diabetes with a 10-year follow-up study, the DPP Outcomes Study (DPPOS). We evaluated baseline HbA1c as a predictor of diabetes and determined the effects of treatments on diabetes defined by an HbA1c ≥6.5% (48 mmol/mol). RESEARCH DESIGN AND METHODS We randomized 3,234 nondiabetic adults at high risk of diabetes to placebo, metformin, or intensive lifestyle intervention and followed them for the development of diabetes as diagnosed by fasting plasma glucose (FPG) and 2-h postload glucose (2hPG) concentrations (1997 American Diabetes Association [ADA] criteria). HbA1c was measured but not used for study eligibility or outcomes. We now evaluate treatment effects in the 2,765 participants who did not have diabetes at baseline according to FPG, 2hPG, or HbA1c (2010 ADA criteria). RESULTS Baseline HbA1c predicted incident diabetes in all treatment groups. Diabetes incidence defined by HbA1c ≥6.5% was reduced by 44% by metformin and 49% by lifestyle during the DPP and by 38% by metformin and 29% by lifestyle throughout follow-up. Unlike the primary DPP and DPPOS findings based on glucose criteria, metformin and lifestyle were similarly effective in preventing diabetes defined by HbA1c. CONCLUSIONS HbA1c predicted incident diabetes. In contrast to the superiority of the lifestyle intervention on glucose-defined diabetes, metformin and lifestyle interventions had similar effects in preventing HbA1c-defined diabetes. The long-term implications for other health outcomes remain to be determined. PMID:25336746

  3. The Effect of Prolonged Glucosamine Usage on HbA1c Levels and New-Onset Diabetes Mellitus in Overweight and Obese Middle-Aged Women.

    Science.gov (United States)

    Gommans, Yvonne M M; Runhaar, Jos; Jacobs, Marloes L; Bierma-Zeinstra, Sita M A

    2017-06-01

    The aim of the present study was to evaluate the effect of a 2.5-year glucosamine sulfate intervention on hemoglobin A1c (HbA1c) levels and the incidence of new-onset diabetes mellitus over 6.5 years in middle-aged women with a body mass index ≥27 kg/m 2 . In total, 407 women were randomized into either oral crystalline glucosamine sulfate or placebo. At baseline, 1 year, 2.5 years, and 6.5 years, a blood sample for the HbA1c level was drawn and questionnaires were taken. After 6.5 years there were missing data for some variables, therefore, multiple imputation was used. With the imputed data, a generalized estimating equation was performed to analyze the effect of glucosamine sulfate usage over 6.5 years. Finally, these analyses were rerun for the 2 subgroups of participants with and without high HbA1c level (≥42 mmol/mol) at baseline. There was no significant effect of a 2.5-year glucosamine sulfate intervention on mean HbA1c level or on obtaining a high HbA1c level or new-onset diabetes mellitus over 6.5 years. The subgroup analyses of participants with and without high HbA1c level at baseline were also not statistically significant. However, participants with a high HbA1c level at baseline had higher odds ratios compared with the participants with a normal HbA1c at baseline. There was no effect of glucosamine sulfate on mean HbA1c level nor on obtaining a high HbA1c level or new-onset diabetes mellitus over 6.5 years, especially in participants with a normal HbA1c level at baseline. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Association of glycated albumin to HbA1c ratio with diabetic retinopathy but not diabetic nephropathy in patients with type 2 diabetes.

    Science.gov (United States)

    Umayahara, Yutaka; Fujita, Yohei; Watanabe, Hirotaka; Kasai, Noriko; Fujiki, Noritaka; Hatazaki, Masahiro; Koga, Masafumi

    2017-04-01

    The ratio of glycated albumin to HbA1c (GA/HbA1c ratio) is a known indicator that reflects fluctuations in plasma glucose. In this study, the association of the GA/HbA1c ratio to diabetic nephropathy and diabetic retinopathy in patients with type 2 diabetes was investigated. Among patients with type 2 diabetes, 613 patients (364 males and 249 females, aged 63.2±12.5, body mass index (BMI) 25.4±4.8kg/m 2 ) were enrolled. Patients with overt proteinuria, reduced renal function, or anemia were excluded. In a comparison between patients with and without diabetic nephropathy, significance was observed in insulin therapy, HbA1c, and GA. In addition, in a comparison between patients with and without diabetic retinopathy, the GA/HbA1c ratio along with insulin therapy, HbA1c, and GA showed significant differences. When the GA/HbA1c ratios were divided into three groups and compared, the rates of diabetic nephropathy did not show any significance, while the rate of diabetic retinopathy increased significantly as the GA/HbA1c ratio increased. In multivariable analyses, while insulin therapy and BMI were the significant independent variables for diabetic nephropathy, insulin therapy and the GA/HbA1c ratios were the significant independent variable for diabetic retinopathy. The GA/HbA1c ratio was associated with diabetic retinopathy, but not with diabetic nephropathy in patients with type 2 diabetes. These results suggest that the development and progression of diabetic retinopathy is associated with plasma glucose fluctuations. Copyright © 2016 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  5. Up-regulation of HB-EGF by the COX-2/PGE2 signaling associates with the cisplatin resistance and tumor recurrence of advanced HNSCC.

    Science.gov (United States)

    Yang, Cheng-Chieh; Tu, Hsi-Feng; Wu, Cheng-Hsien; Chang, Hsiu-Chuan; Chiang, Wei-Fan; Shih, Nai-Chia; Lee, Yong-Syu; Kao, Shou-Yen; Chang, Kuo-Wei

    2016-05-01

    When treating advanced HNSCC, a cisplatin-based systemic regimen benefit patient survival. However, chemoresistance will greatly reduce the effectiveness of this approach. The identification of molecules that contribute to cisplatin resistance may potentially improve the survival. Both HB-EGF and COX-2 have been reported to increase cisplatin-resistance. Here, we have focused on the regulation of HB-EGF/COX-2 and their roles in cisplatin resistance. IHC staining was used to measure the expression levels of HB-EGF and COX-2 on the tissue microarray from 43 tissue samples of patients with advanced HNSCC. siRNA, western blot and qRT-PCR were used to dissect the regulation between EGF, Akt, COX-2, PGE2, and cisplatin sensitivity. The correlation between HB-EGF, COX2 and HNSCC progression was analyzed by the receiver operating characteristic (ROC) curve and Kaplan-Meier disease free survival. Patients of advanced HNSCC patients with increased HB-EGF and COX-2 expression have higher tumor recurrent rates that was related to cisplatin resistance. The resistance was mediated via an increased expression of HB-EGF and COX-2. The activation of Akt by either EGF or areca nut extract were able to upregulate COX-2, which would increase the expression of HB-EGF in a PGE2 dependent manner. Inhibition and knockdown of COX-2 resulted in a decrease in HB-EGF. In the tissue samples from HNSCC patients, there was a significant positive correlation between the expression of COX-2 and HB-EGF. Our results suggested that COX-2 and HB-EGF are important in development of HNSCC cisplatin resistance. These findings may help the development of new strategies for overcoming cisplatin resistance. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. A two-step screening, measurement of HbA1c in association with FPG, may be useful in predicting diabetes.

    Directory of Open Access Journals (Sweden)

    Kyoko Nomura

    Full Text Available BACKGROUNDS: We compared the usefulness of fasting plasma glucose (FPG, or hemoglobin A1c (HbA1c, or both in predicting type 2 diabetes. METHODS: This retrospective cohort study investigated 9,322 Japanese adults (4,786 men and 4,536 women, aged 19-69 yrs, free of diabetes at baseline. Usefulness was assessed by predictive values (PV, sensitivity, specificity, and the area under the receiver operating characteristic curve (AUROC maximised under the best cut-off point. RESULTS: During the average 6 years of follow-up, 221 men (4.6% and 92 women (2% developed diabetes. The best cut-off points for FPG (i.e., 5.67 mmol/l for men and 5.5 mmol/l for women gave excellent AUROC, and the highest positive PV (13% for men and 9% for women in predicting diabetes. In high risk subjects with FPG 6.1-6.9 mmol/l, 119 men (26.8% and 39 women (28.3% developed diabetes. Under the best cut-off points of FPG 6.39 mmol/l and A1c 5.8, AUROC and positive PV for FPG slightly decreased indicating FPG became less useful and were statistically indistinguishable from those for HbA1c in men. In fact, HbA1c was the most useful in women: HbA1c of 6.0% gave the highest positive likelihood ratio of 2.74 and larger AUROC than did FPG. Although AUROC for HbA1c was acceptable and indistinguishable from that for the combined use, HbA1c had higher specificity and positive LR than did the combined use. CONCLUSIONS: This study demonstrated that FPG was the most useful to predict diabetes in the general population. However, in subjects with FPG 6.1-6.9 mmol/l, FPG became less useful and diagnostic performance of FPG was indistinguishable from that of HbA1c in men whereas HbA1c was the most useful in women. Thus, a two-step screening, measurement of HbA1c in association with FPG, may be useful in predicting diabetes.

  7. Registration of Food Barley (Hordeum vulgare L.) Variety HB 1307 ...

    African Journals Online (AJOL)

    Six-rowed food type barley, HB 1307, was developed by Holetta Agricultural Research Center (HARC) from a cross between a landrace line and exotic germplasm (Awra gebs-1 x IBON93/91) and released in 2006 for mid and high altitude areas. The three consecutive years\\' (2002-2004) tests proved its superiority in grain ...

  8. Determining the Threshold for HbA1c as a Predictor for Adverse Outcomes After Total Joint Arthroplasty: A Multicenter, Retrospective Study.

    Science.gov (United States)

    Tarabichi, Majd; Shohat, Noam; Kheir, Michael M; Adelani, Muyibat; Brigati, David; Kearns, Sean M; Patel, Pankajkumar; Clohisy, John C; Higuera, Carlos A; Levine, Brett R; Schwarzkopf, Ran; Parvizi, Javad; Jiranek, William A

    2017-09-01

    Although HbA1c is commonly used for assessing glycemic control before surgery, there is no consensus regarding its role and the appropriate threshold in predicting adverse outcomes. This study was designed to evaluate the potential link between HbA1c and subsequent periprosthetic joint infection (PJI), with the intention of determining the optimal threshold for HbA1c. This is a multicenter retrospective study, which identified 1645 diabetic patients who underwent primary total joint arthroplasty (1004 knees and 641 hips) between 2001 and 2015. All patients had an HbA1c measured within 3 months of surgery. The primary outcome of interest was a PJI at 1 year based on the Musculoskeletal Infection Society criteria. Secondary outcomes included orthopedic (wound and mechanical complications) and nonorthopedic complications (sepsis, thromboembolism, genitourinary, and cardiovascular complications). A regression analysis was performed to determine the independent influence of HbA1c for predicting PJI. Overall 22 cases of PJI occurred at 1 year (1.3%). HbA1c at a threshold of 7.7 was distinct for predicting PJI (area under the curve, 0.65; 95% confidence interval, 0.51-0.78). Using this threshold, PJI rates increased from 0.8% (11 of 1441) to 5.4% (11 of 204). In the stepwise logistic regression analysis, PJI remained the only variable associated with higher HbA1c (odds ratio, 1.5; confidence interval, 1.2-2.0; P = .0001). There was no association between high HbA1c levels and other complications assessed. High HbA1c levels are associated with an increased risk for PJI. A threshold of 7.7% seems to be more indicative of infection than the commonly used 7% and should perhaps be the goal in preoperative patient optimization. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Are There Clinical Implications of Racial Differences in HbA1c? A Difference, to Be a Difference, Must Make a Difference

    Science.gov (United States)

    Selvin, Elizabeth

    2016-01-01

    Studies that have compared HbA1c levels by race have consistently demonstrated higher HbA1c levels in African Americans than in whites. These racial differences in HbA1c have not been explained by measured differences in glycemia, sociodemographic factors, clinical factors, access to care, or quality of care. Recently, a number of nonglycemic factors and several genetic polymorphisms that operate through nonglycemic mechanisms have been associated with HbA1c. Their distributions across racial groups and their impact on hemoglobin glycation need to be systematically explored. Thus, on the basis of evidence for racial differences in HbA1c, current clinical guidelines from the American Diabetes Association state: “It is important to take…race/ethnicity…into consideration when using the A1C to diagnose diabetes.” However, it is not clear from the guidelines how this recommendation might be actualized. So, the critical question is not whether racial differences in HbA1c exist between African Americans and whites; the important question is whether the observed differences in HbA1c level are clinically meaningful. Therefore, given the current controversy, we provide a Point-Counterpoint debate on this issue. In the preceding point narrative, Dr. Herman provides his argument that the failure to acknowledge that HbA1c might be a biased measure of average glycemia and an unwillingness to rigorously investigate this hypothesis will slow scientific progress and has the potential to do great harm. In the counterpoint narrative below, Dr. Selvin argues that there is no compelling evidence for racial differences in the validity of HbA1c as a measure of hyperglycemia and that race is a poor surrogate for differences in underlying causes of disease risk. —William T. Cefalu Editor in Chief, Diabetes Care PMID:27457637

  10. Molecular characterization of a heme-binding protein of Bacteroides fragilis BE1.

    OpenAIRE

    Otto, B R; Kusters, J G; Luirink, J; de Graaf, F K; Oudega, B

    1996-01-01

    An iron-repressible 44-kDa outer membrane protein plays a crucial role in the acquisition of heme by the anaerobic bacterium Bacteroides fragilis. The DNA sequence of the gene encoding the 44-kDa protein (hupA) was determined. The hupA gene encodes a protein of 431 amino acid residues with a calculated molecular mass of 48,189 Da. The hupA gene is preceded by an open reading frame of 480 bp that probably encodes a protein with a calculated molecular mass of 18,073 Da. hupA and this open readi...

  11. Efficacy and safety of total dose infusion of low molecular weight iron dextran in the treatment of iron deficiency anemia during pregnancy

    International Nuclear Information System (INIS)

    Ayub, R.; Tariq, N.; Iqbal, M.; Jafery, T.

    2008-01-01

    To determine the efficacy and safety of Total Dose Infusion (TDI) of low molecular weight iron dextran for the treatment of iron deficiency anemia compared to oral iron replacement during pregnancy through improvement in hemoglobin (Hb) after intervention. Non-randomized control trial. A group of 100 pregnant women with gestational age greater than 12 weeks with confirmed diagnosis of iron deficiency anemia attending the antenatal clinics were enrolled in this study. Total dose iron infusion of low molecular iron dextran was given to these patients after calculating iron deficit, in a monitored in-patient setting. Control comprised of a second group of 50 pregnant females matched for age, parity and baseline hemoglobin, tolerant to oral iron supplementation (ferrous sulphate 200 mg three times a day) attending the antenatal clinics during the same period. Post-treatment hemoglobin levels of study group as well as the oral control group were determined between 3 to 4 weeks. In the intervention group, mean pre-infusion hemoglobin level was 8.57 +- 0.9 gm/dl (range 5-10.5 gm/dl) and mean post-infusion Hb was 11.0 +- 1.1 (range 8.4-14.3 gm/dl). In control group, mean pre-oral intake Hb level was 9.5 +- 0.9 gm/dl (range 7-10.5 gm/dl) and mean post-oral intake Hb was 10.2 +- 1.2 gm/dl (range 6.4-12.8 gm/dl). Mean increase of Hb in intervention group was 2.43 gm/dl (95% CI 2.4 - 3.8) and for controls it was 0.7 gm/dl (95% CI 0.6-2.3). Flushing and palpitations were observed in 4% of interventional group patients and none in the control group. No significant adverse reactions were observed in either group. We conclude that the total parenteral iron replacement with low molecular weight iron dextran is an effective and safe method for the treatment of iron deficiency anemia in a selected group of pregnant women. (author)

  12. Development of novel antibacterial active, HaCaT biocompatible and biodegradable CA-g-P(3HB-EC biocomposites with caffeic acid as a functional entity

    Directory of Open Access Journals (Sweden)

    H. M. N. Iqbal

    2015-09-01

    Full Text Available We have developed novel composites by grafting caffeic acid (CA onto the P(3HB-EC based material and laccase from Trametes versicolor was used for grafting purposes. The resulting composites were designated as CA-g-P(3HB-EC i.e., P(3HB-EC (control, 5CA-g-P(3HB-EC, 10CA-g-P(3HB-EC, 15CA-g-P(3HB-EC and 20CA-g-P(3HB-EC. FT-IR (Fourier-transform infrared spectroscopy was used to examine the functional and elemental groups of the control and laccase-assisted graft composites. Evidently, 15CA-g-P(3HB-EC composite exhibited resilient antibacterial activity against Gram-positive and Gram-negative bacterial strains. Moreover, a significant level of biocompatibility and biodegradability of the CA-g-P(3HB-EC composites was also achieved with the human keratinocytes-like HaCaT cells and soil burial evaluation, respectively. In conclusion, the newly developed novel composites with multi characteristics could well represent the new wave of biomaterials for medical applications, and more specifically have promising future in the infection free would dressings, burn and/or skin regeneration field due to their sophisticated characteristics.

  13. Evaluation of hydrogen bond networks in cellulose Iβ and II crystals using density functional theory and Car-Parrinello molecular dynamics.

    Science.gov (United States)

    Hayakawa, Daichi; Nishiyama, Yoshiharu; Mazeau, Karim; Ueda, Kazuyoshi

    2017-09-08

    Crystal models of cellulose Iβ and II, which contain various hydrogen bonding (HB) networks, were analyzed using density functional theory and Car-Parrinello molecular dynamics (CPMD) simulations. From the CPMD trajectories, the power spectra of the velocity correlation functions of hydroxyl groups involved in hydrogen bonds were calculated. For the Iβ allomorph, HB network A, which is dominant according to the neutron diffraction data, was stable, and the power spectrum represented the essential features of the experimental IR spectra. In contrast, network B, which is a minor structure, was unstable because its hydroxymethyl groups reoriented during the CPMD simulation, yielding a different crystal structure to that determined by experiments. For the II allomorph, a HB network A is proposed based on diffraction data, whereas molecular modeling identifies an alternative network B. Our simulations showed that the interaction energies of the cellulose II (B) model are slightly more favorable than model II(A). However, the evaluation of the free energy should be waited for the accurate determination from the energy point of view. For the IR calculation, cellulose II (B) model reproduces the spectra better than model II (A). Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. The sunflower transcription factor HaHB11 improves yield, biomass and tolerance to flooding in transgenic Arabidopsis plants.

    Science.gov (United States)

    Cabello, Julieta V; Giacomelli, Jorge I; Piattoni, Claudia V; Iglesias, Alberto A; Chan, Raquel L

    2016-03-20

    HaHB11 is a member of the sunflower homeodomain-leucine zipper I subfamily of transcription factors. The analysis of a sunflower microarray hybridized with RNA from HaHB11-transformed leaf-disks indicated the regulation of many genes encoding enzymes from glycolisis and fermentative pathways. A 1300bp promoter sequence, fused to the GUS reporter gene, was used to transform Arabidopsis plants showing an induction of expression after flooding treatments, concurrently with HaHB11 regulation by submergence in sunflower. Arabidopsis transgenic plants expressing HaHB11 under the control of the CaMV 35S promoter and its own promoter were obtained and these plants exhibited significant increases in rosette and stem biomass. All the lines produced more seeds than controls and particularly, those of high expression level doubled seeds yield. Transgenic plants also showed tolerance to flooding stress, both to submergence and waterlogging. Carbohydrates contents were higher in the transgenics compared to wild type and decreased less after submergence treatments. Finally, transcript levels of selected genes involved in glycolisis and fermentative pathways as well as the corresponding enzymatic activities were assessed both, in sunflower and transgenic Arabidopsis plants, before and after submergence. Altogether, the present work leads us to propose HaHB11 as a biotechnological tool to improve crops yield, biomass and flooding tolerance. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. Estimation of biological variation and reference change value of glycated hemoglobin (HbA(1c)) when two analytical methods are used.

    Science.gov (United States)

    Ucar, Fatma; Erden, Gonul; Ginis, Zeynep; Ozturk, Gulfer; Sezer, Sevilay; Gurler, Mukaddes; Guneyk, Ahmet

    2013-10-01

    Available data on biological variation of HbA1c revealed marked heterogeneity. We therefore investigated and estimated the components of biological variation for HbA1c in a group of healthy individuals by applying a recommended and strictly designed study protocol using two different assay methods. Each month, samples were derived on the same day, for three months. Four EDTA whole blood samples were collected from each individual (20 women, 9 men; 20-45 years of age) and stored at -80°C until analysis. HbA1c values were measured by both high performance liquid chromatography (HPLC) (Shimadzu, Prominence, Japan) and boronate affinity chromatography methods (Trinity Biotech, Premier Hb9210, Ireland). All samples were assayed in duplicate in a single batch for each assay method. Estimations were calculated according to the formulas described by Fraser and Harris. The within subject (CV(I))-between subject (CV(G)) biological variations were 1.17% and 5.58%, respectively for HPLC. The calculated CV(I) and CV(G) were 2.15% and 4.03%, respectively for boronate affinity chromatography. Reference change value (RCV) for HPLC and boronate affinity chromatography was 5.4% and 10.4% respectively and individuality index of HbA(1c) was 0.35 and 0.93 respectively. This study for the first time described the components of biological variation for HbA1c in healthy individuals by two different assay methods. Obtained findings showed that the difference between CV(A) values of the methods might considerably affect RCV. These data regarding biological variation of HbA(1c) could be useful for a better evaluation of HbA(1c) test results in clinical interpretation. Copyright © 2013 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  16. Diagnostic performance of HbA1c for diabetes in Arab vs. European populations: a systematic review and meta-analysis.

    Science.gov (United States)

    Bertran, E A; Berlie, H D; Taylor, A; Divine, G; Jaber, L A

    2017-02-01

    To examine differences in the performance of HbA 1c for diagnosing diabetes in Arabs compared with Europeans. The PubMed, Embase and Cochrane library databases were searched for records published between 1998 and 2015. Estimates of sensitivity, specificity and log diagnostic odds ratios for an HbA 1c cut-point of 48 mmol/mol (6.5%) were compared between Arabs and Europeans, using a bivariate linear mixed-model approach. For studies reporting multiple cut-points, population-specific summary receiver operating characteristic (SROC) curves were constructed. In addition, sensitivity, specificity and Youden Index were estimated for strata defined by HbA 1c cut-point and population type. Database searches yielded 1912 unique records; 618 full-text articles were reviewed. Fourteen studies met the inclusion criteria; hand-searching yielded three additional eligible studies. Three Arab (N = 2880) and 16 European populations (N = 49 127) were included in the analysis. Summary sensitivity and specificity for a HbA 1c cut-point of 48 mmol/mol (6.5%) in both populations were 42% (33-51%), and 97% (95-98%). There was no difference in area under SROC curves between Arab and European populations (0.844 vs. 0.847; P = 0.867), suggesting no difference in HbA 1c diagnostic accuracy between populations. Multiple cut-point summary estimates stratified by population suggest that Arabs have lower sensitivity and higher specificity at a HbA 1c cut-point of 44 mmol/mol (6.2%) compared with European populations. Estimates also suggest similar test performance at cut-points of 44 mmol/mol (6.2%) and 48 mmol/mol (6.5%) for Arabs. Given the low sensitivity of HbA 1c in the high-risk Arab American population, we recommend a combination of glucose-based and HbA 1c testing to ensure an accurate and timely diagnosis of diabetes. © 2016 Diabetes UK.

  17. Periodontal inflamed surface area and C-reactive protein as predictors of HbA1c: a study in Indonesia.

    Science.gov (United States)

    Susanto, Hendri; Nesse, Willem; Dijkstra, Pieter U; Hoedemaker, Evelien; van Reenen, Yvonne Huijser; Agustina, Dewi; Vissink, Arjan; Abbas, Frank

    2012-08-01

    Periodontitis may exert an infectious and inflammatory burden, evidenced by increased C-reactive protein (CRP). This burden may impair blood glucose control (HbA1c). The aim of our study was to analyze whether periodontitis severity as measured with the periodontal inflamed surface area (PISA) and CRP predict HbA1c levels in a group of healthy Indonesians and a group of Indonesians treated for type 2 diabetes mellitus (DM2). A full-mouth periodontal examination, including probing pocket depth, gingival recession, clinical attachment loss, plaque index and bleeding on probing, was performed in 132 healthy Indonesians and 101 Indonesians treated for DM2. Using these data, PISA was calculated. In addition, HbA1c and CRP were analyzed. A validated questionnaire was used to assess smoking, body mass index (BMI), education and medical conditions. In regression analyses, it was assessed whether periodontitis severity and CRP predict HbA1c, controlling for confounding and effect modification (i.e., age, sex, BMI, pack years, and education). In healthy Indonesians, PISA and CRP predicted HbA1c as did age, sex, and smoking. In Indonesians treated for DM2, PISA did not predict HbA1c. Periodontitis may impair blood glucose regulation in healthy Indonesians in conjunction with elevated CRP levels. The potential effect of periodontitis on glucose control in DM2 patients may be masked by DM2 treatment. periodontitis may impair blood glucose control through exerting an inflammatory and infectious burden evidenced by increased levels of CRP.

  18. Common Hemoglobin Variants in Southern Taiwan and Their Effect on the Determination of HbA1c by Ion-exchange High-performance Liquid Chromatography

    Directory of Open Access Journals (Sweden)

    Chih-Hsun Chu

    2009-07-01

    Conclusion: The existence of Hb variants may result in false HbA1c measurement. The possible presence of spuriously low HbA1c levels or abnormal HPLC chromatograms by using ion-exchange methods should be kept in mind.

  19. Relationship between Plasma Ferritin Level and Siderocyte Number in Splenectomized β-Thalassemia/HbE Patients

    Directory of Open Access Journals (Sweden)

    A. Tripatara

    2012-01-01

    Full Text Available Introduction. In iron overload status, excess iron deposits in reticuloendothelial cells and tissues and can be detected using Prussian blue staining. The aim of this paper was to investigate the relationship between siderocyte numbers and plasma ferritin levels (a practically standard marker of iron overload in the blood of the splenectomized and nonsplenectomized β-thalassemia/HbE patients, who are at risk of iron overload. Methods. EDTA blood samples from 64 patients with 35 splenectomized and 29 nonsplenectomized β-thalassemia/HbE patients, who received regular blood transfusions, and 20 normal individuals were investigated for siderocyte numbers, plasma ferritin levels, and complete blood counts. Results. The average percent siderocytes in splenectomized and nonsplenectomized β-thalassemia/HbE patients were 11.5% and 0.08%, respectively, and plasma ferritin levels of 2,332 μg/L and 1,279 μg/L, respectively. Percent siderocytes showed a good correlation with plasma ferritin levels only in splenectomized patients (r=0.69, P<0.001. A receiver operating curve analysis from splenectomized patients’ data indicated that siderocytes at 3% cut-off are the best predictor for plasma ferritin level ≥1,000 μg/L with 92.9% sensitivity and 42.9% specificity. Conclusion. Circulating siderocyte numbers can be used as a screening test for the assessment of the iron overload in splenectomized β-thalassemia/HbE patients in the place where serum ferritin is not available.

  20. ST6Gal1, Cox-2 and HB-EGF mRNA Expression in Breast Cancer

    Directory of Open Access Journals (Sweden)

    Aliakbar Taherian

    2015-01-01

    Full Text Available Background: ST6Gal1, Cox-2 and HB-EGF genes are involved in different tumors and their enhanced expressions often correlate with poor prognosis. In this study we assay the expressions of these genes by reverse transcriptase-PCR in 54 breast cancer samples. Methods: Tissue samples were either formalin-fixed for histopathological examination or frozen for reverse transcriptase-PCR. Image program was used for the densitometry of the image of the gels and the expression of different genes was normalized with beta actin expression. The student's t-test and correlation matrix were used for data analyses. Results: We observed significantly higher expressions of ST6Gal1 (P= 0.040, Cox- 2 (P= 0.001 and HB-EGF (P= 0.009 in the tumor region compared to the margin samples. A significant correlation was found between HB-EGF and Cox-2 expression (P= 0.001. There was a positive correlation between total score, tumor size, histology grade and nuclear grade but there was a reverse correlation between age and tumor size, histology grade and total score. Conclusion: Expressions of ST6Gal1, Cox-2 and HB-EGF in breast tumor samples in this and a number of other studies emphasize their role as important markers in breast cancer. The use of medications to inhibit either their individual expressions or the possible inhibition of all three genes may improve patient survival and prevent metastasis.

  1. Extreme Levels of HbA1c Increase Incident ESRD Risk in Chinese Patients with Type 2 Diabetes: Competing Risk Analysis in National Cohort of Taiwan Diabetes Study

    Science.gov (United States)

    Liu, Chiu-Shong; Huang, Chiu-Ching; Lin, Wen-Yuan; Chiang, Jen-Huai; Lin, Cheng-Chieh; Li, Tsai-Chung

    2015-01-01

    Background Whether HbA1c is a predictor of end-stage renal disease (ESRD) in type 2 diabetes patients remains unclear. This study evaluated relationship between HbA1c and ESRD in Chinese patients with type 2 diabetes. Methods Patients aged ≥ 30 years who were free of ESRD (n = 51 681) were included from National Diabetes Care Management Program from 2002–2003. Extended Cox proportional hazard model with competing risk of death served to evaluate association between HbA1c level and ESRD. Results A total of 2613 (5.06%) people developed ESRD during a follow-up period of 8.1 years. Overall incidence rate of ESRD was 6.26 per 1000 person-years. Patients with high levels of HbA1c had a high incidence rate of ESRD, from 4.29 for HbA1c of  6.0%–6.9% to 10.33 for HbA1c ≥ 10.0% per 1000 person-years. Patients with HbA1c HbA1c  of 6.0%–6.9%. A J-shaped relationship between HbA1c level and ESRD risk was observed. After adjustment, patients with HbA1c HbA1c of 6.0%–6.9%. Conclusions Diabetes care has focused on preventing hyperglycemia, but not hypoglycemia. Our study revealed that HbA1c level ≥ 7.0% was linked with increased ESRD risk in type 2 diabetes patients, and that HbA1c HbA1c targets and improve outcomes without increasing the risk to this population. Clinicians need to pay attention to HbA1c results on diabetic nephropathy. PMID:26098901

  2. Estudos QSAR e Ancoragem Molecular de Inibidores da Atividade Biológica do Fator de Inibição da Migração dos Macrófagos (MIF

    Directory of Open Access Journals (Sweden)

    Alex Gutterres Taranto

    2012-08-01

    Full Text Available Cumarina e 4-Cromonas são promissores inibidores de fator inibição da migração de macrófagos (MIF, uma proteína envolvida em doenças inflamatórias, como artrite reumatóide e outras patologias. Estudos teóricos de QSAR e ancoragem molecular de um conjunto de compostos mostraram correlação com estudos experimentais. Os descritores doadores de ligação hidrogênio e momento dipolo total foram capazes de prever atividade inibitória de compostos contra o MIF (MIFi . Paralelamente, estudos de ancoragem molecular também foram capazes de identificar ligações hidrogênio e hidrofóbicas entre os ligantes e o MIF. Como resultado, ambas as metodologias mostraram as contribuições de ligação de hidrogênio e interações hidrofóbicas para explicar a atividade de compostos inibidores de MIF, descrevendo os grupos farmacofóricos destes compostos. Adicionalmente, um conjunto de cumarinas naturais e sintéticas foi submetido aos modelos QSAR e de ancoragem molecular a fim de que as suas atividades contra MIF fossem preditas. Ambas as metodologias de modelagem molecular puderam estimar as interações intermoleculares entre inibidores e a enzima, os quais foram muito similares a compostos descritos previamente. Estes resultados podem ser úteis para o desenho de novos compostos contra doenças inflamatórias como artrite reumatóide.

  3. Detecção de potenciais marcadores moleculares séricos da doença de Hodgkin Detection of potential serum molecular markers for Hodgkin's disease

    Directory of Open Access Journals (Sweden)

    Paulo Costa Carvalho

    2005-06-01

    Full Text Available MOTIVAÇÃO: Neste trabalho foi analisado o perfil de proteínas séricas de pacientes com doença de Hodgkin (DH localizada e avançada em busca de novos e potenciais biomarcadores para o diagnóstico médico. MATERIAIS E MÉTODOS: O perfil de proteínas presentes no soro de 14 indivíduos saudáveis, 14 pacientes com DH avançada e 15 pacientes com DH localizada, assim como pools de soro dos respectivos grupos, foi analisado em gel desnaturante de poliacrilamida a 12% corado pela prata. A densitometria e a intensidade média das bandas de interesse foram estudadas utilizando-se o Kodak 1D Scientific Imaging System. RESULTADOS E CONCLUSÕES: O perfil protéico apresentou acentuada variação entre os pacientes examinados; entretanto foi observada a indução predominante de determinadas proteínas (aproximadamente 26kDa e 18kDa, cuja expressão foi substancialmente diferente quando em comparação com os controles (p AIM: In this work the serum protein profile of patients with localized and advanced Hodgkin's disease (HD was analyzed to search for new potential biomarkers of medical interest. MATERIALS AND METHODS: The serum protein profile of 14 healthy donors, 14 patients with advanced disease, 15 patients with localized disease and serum pools of the respective groups, were analyzed using silver stained 12% denaturating polyacrylamide gel. The densitometry and mean band intensity from the bands of interest were analyzed using the Kodak 1D Scientific Imaging System. RESULTS AND CONCLUSION: The patients' protein profiles presented heterogenous variations; however over-expressed proteins of approximately 26kDa and 18kDa were proven to be statistically different when compared to healthy donors. Such proteins could potentially constitute in molecular markers for diagnosis and patient treatment follow-up.

  4. National Survey on Internal Quality Control for HbA(1c) Analytical Instruments in 331 Hospital Laboratories of China.

    Science.gov (United States)

    Zeng, Rong; Wang, Wei; Zhao, Haijian; Fei, Yang; Wang, Zhiguo

    2015-01-01

    The narrow gap of HbA1 value of mass fraction between "normal" (control of inter-assay standardization, assay precision, and trueness. This survey was initiated to obtain knowledge of the current situation of internal quality control (IQC) practice for HbA(1c) in China and find out the most appropriate quality specifications. Data of IQC for HbA(1c) in 331 institutions participating in the national proficiency testing (PT) programs in China were evaluated using four levels of quality specifications, and the percentages of laboratories meeting the quality requirement were calculated to find out the most appropriate quality specifications for control materials of HbA(1c) in China. The IQC data varied vastly among 331 clinical laboratories in China. The measurement of control materials covered a wide range from 4.52% to 12.24% (inter-quartile range) and there were significant differences among the CVs of different methods, including LPLC, CE-HPLC, AC-HPLC, immunoturbidimetry, and others. Among the four main methods, CE-HPLC and AC-HPLC achieved a better precision. As we can see, the performance of laboratories for HbA(1c) has yet to be improved. Clinical laboratories in China should improve their performance with a stricter imprecision criteria.

  5. 31P NMR spectroscopy and HbO2 cryospectrophotometry in prediction of tumor radioresistance caused by hypoxia.

    Science.gov (United States)

    Rofstad, E K; DeMuth, P; Fenton, B M; Ceckler, T L; Sutherland, R M

    1989-04-01

    The aim of this study was to search for possible relationships between the fraction of radiobiologically hypoxic cells in tumors and their 31P NMR spectral parameters and intracapillary HbO2 saturations. Four different tumor lines, two murine sarcomas (KHT, RIF-1) and two human ovarian carcinoma xenografts (MLS, OWI), were used. When tumor volume increased from about 200 mm3 to about 2000 mm3, hypoxic fraction increased from 12 to 23% for the KHT line, from 0.9 to 1.7% for the RIF-1 line, and from 9 to 28% for the MLS line. The OWI line showed similar hypoxic fractions at 200 (17%) and 2000 mm3 (15%). Tumor bioenergetic status decreased, that is, the inorganic phosphate (Pi) resonance increased and the phosphocreatine (PCr) and nucleoside triphosphate beta (NTP beta) resonances decreased, with increasing tumor volume for the KHT, RIF-1, and MLS lines, whereas the OWI line did not show any changes in the 31P NMR spectral parameters during tumor growth. Similarly, tumor HbO2 saturation status, that is, the fraction of vessels with HbO2 saturation above 30%, decreased with increasing tumor volume for the KHT, RIF-1, and MLS lines, but remained unchanged during tumor growth for the OWI line. Although the data indicated a relationship between hypoxic fraction and tumor bioenergetic status as well as tumor HbO2 saturation status within a specific line during tumor growth, there was no correlation between hypoxic fraction and tumor bioenergetic status or tumor HbO2 saturation status across the four tumor lines. This may have occurred because cell survival time under hypoxic stress as well as fraction of non-clonogenic, but metabolically active hypoxic cells differed among the tumor lines. This indicates that 31P NMR spectroscopy and HbO2 cryospectrophotometry data have to be supplemented with other data to be useful in prediction of tumor radioresistance caused by hypoxia.

  6. Effect of iron deficiency anemia and iron supplementation on HbA1c levels - Implications for diagnosis of prediabetes and diabetes mellitus in Asian Indians.

    Science.gov (United States)

    Madhu, S V; Raj, Abhishek; Gupta, Stuti; Giri, S; Rusia, Usha

    2017-05-01

    We investigated the effect of iron deficiency anemia (IDA) on levels of glycated hemoglobin (HbA1c) and to compare its levels before and after iron supplementations. Age and sex matched subjects were enrolled and clustered in 2 groups: IDA (n=62) and healthy controls (HC; n=60). HbA1c levels were estimated by HPLC. Hemogram were estimated by hematology analyser. Serum ferritin (ELISA) and other parameters of iron profile were measured by standard guidelines of ICSH. HbA1c values and iron studies were repeated after 3months of iron supplementation to determine the effect of iron therapy on HbA1c levels. Significantly higher HbA1c levels were observed in IDA subjects compared to HC (5.51±0.696 v/s 4.85±0.461%, pHbA1c and hemoglobin, hematocrit, RBC count, MCH, MCHC and serum ferritin in IDA subjects (r=-0.632, -0.652, -0.384, -0.236, -0.192 and -0.441). Significant decline was noticed in HbA1c levels in IDA subjects after iron supplementation (5.51±0.696 before treatment v/s 5.044±0.603 post-treatment; pHbA1c in pre-diabetes range normalised to normal glucose tolerance (NGT) range and out of 6 patients with pre-treatment HbA1c in diabetes range, 5 reverted to pre-diabetes range while 1 of them reverted to the NGT range. Caution must be exercised in interpreting the results of HbA1c in patients of IDA and iron deficiency must be corrected before diagnosing diabetes and pre-diabetes solely on the basis of HbA1c criteria. Copyright © 2016. Published by Elsevier B.V.

  7. Nutritional intervention and impact of polyphenol on glycohemoglobin (HbA1c) in non-diabetic and type 2 diabetic subjects: Systematic review and nmeta-analysis.

    Science.gov (United States)

    Palma-Duran, Susana A; Vlassopoulos, Antonis; Lean, Mike; Govan, Lindsay; Combet, Emilie

    2017-03-24

    Polyphenols have been extensively studied for their antioxidant and anti-inflammatory properties. Recently, their antiglycative actions by oxidative stress modulation have been linked to the prevention of diabetes and associated complications. This article assesses the evidence for polyphenol interventions on glycohemoglobin (HbA1c) in non-diabetic, pre-diabetic, and type 2 diabetes mellitus (T2DM) subjects. A systematic review of polyphenols' clinical trials on HbA1c in humans was performed according to the Preferred Reporting Items for Systematic Review and Meta-Analysis. Thirty-six controlled randomized trials with HbA1c values were included. Polyphenols (extracts, supplements, and foods) were supplemented (28 mg to 1.5 g) for 0.7 to 12 months. Combining all subjects (n = 1954, mean baseline HbA1c = 7.03%, 53 mmol/mol), polyphenol supplementation significantly (P HbA1c% by -0.53 ± 0.12 units (-5.79 ± 0.13 mmol/mol). This reduction was significant (P HbA1c = 7.44%, 58 mmol/mol), with HbA1c% lowered by -0.21 ± 0.04 units (-2.29 ± 0.4 mmol/mol). Polyphenol supplementation had no significant effect (P > 0.21) in the non-diabetic (n = 258, mean baseline HbA1c = 5.47%, 36 mmol/mol) and the pre-diabetic subjects (n = 270, mean baseline HbA1c = 6.06%, 43 mmol/mol) strata: -0.39 ± 0.27 HbA1c% units (-4.3 ± 0.3 mmol/mol), and -0.38 ± 0.31 units (-4.2 ± 0.31 mmol/mol), respectively. In conclusion, polyphenols can successfully reduce HbA1c in T2DM without any intervention at glycemia, and could contribute to the prevention of diabetes complications.

  8. Prenatal control of Hb Bart's hydrops fetalis: a two-year experience at a mainland Chinese hospital.

    Science.gov (United States)

    Liao, Can; Pan, Min; Han, Jin; Yang, Xin; Zhen, Li; Li, Jian; Li, Ru; Li, Dong-Zhi

    2015-03-01

    α-Thalassemia is a common inherited disease in southern China. The severest form is Hb Bart's hydrops fetalis, in which the affected fetuses almost always die in utero or shortly after birth, and the mothers are at high risk for severe morbidity. Therefore, this condition should be controlled, especially prenatally. In this study, we reported on a two-year experience in prenatal control of Hb Bart's hydrops fetalis at a mainland Chinese hospital. Totally, 573 pregnancies at risk for Hb Bart's hydrops fetalis were referred and different prenatal procedures were offered depending on the gestational age at presentation. One hundred fifty-two affected fetuses were diagnosed prenatally; among these, only half presented in early gestation, and were terminated in time. Although our prenatal program has successfully prevented the birth of children with severe thalassemia, it does not show a satisfactory outcome, considering the gestational age when an affected pregnancy is terminated.

  9. Risk assessment and HbA1c measurement in Norwegian community pharmacies to identify people with undiagnosed type 2 diabetes – A feasibility study

    Science.gov (United States)

    Kjome, Reidun Lisbet Skeide; Sandberg, Sverre; Sølvik, Una Ørvim

    2018-01-01

    Objectives Determine the feasibility of using a diabetes risk assessment tool followed by HbA1c-measurement in a community-pharmacy setting in Norway. Methods In this longitudinal study two pharmacists in each of three community pharmacies were trained to perform risk assessments, HbA1c-measurements and counselling. Pharmacy customers who were > 18 years old and could understand and speak Norwegian or English were recruited in the pharmacies during a two-months-period. Information about the service was presented in local newspapers, social media, leaflets and posters at the pharmacy. Customers wishing to participate contacted the pharmacy staff. Participants completed a validated diabetes risk test and a background questionnaire including a validated instrument for self-rated health. A HbA1c measurement was performed for individuals with a moderate to high risk of developing diabetes. If HbA1c ≥ 6.5% they were recommended to visit their general practitioner for follow-up. The pharmacies performed internal and external quality control of the HbA1c instrument. Results Of the 211 included participants 97 (46%) were > 50 years old. HbA1c was measured for the 47 participants (22%) with high risk. Thirty-two (15%) had HbA1c values internal and external quality control for HbA1c were within set limits. Conclusion The pharmacists were able to perform the risk assessment and measurement of HbA1c, and pharmacy customers were willing to participate. The HbA1c measurements fulfilled the requirements for analytical quality. Thus, it is feasible to implement this service in community pharmacies in Norway. In a large-scale study the inclusion criteria should be increased to 45 years in accordance with the population the risk test has been validated for. PMID:29474501

  10. The Analysis of the Possible Thermal Emission at Radio Frequencies from an Evolved Supernova Remnant HB 3 (G132.7+1.3: Revisited

    Directory of Open Access Journals (Sweden)

    Onić, D.

    2008-12-01

    Full Text Available It has recently been reported that some of the flux density values for an evolved supernova remnant (SNR HB 3 (G132.7$+$1.3 are not accurate enough. In this work we therefore revised the analysis of the possible thermal emission at radio frequencies from this SNR using the recently published, corrected flux density values. A model including the sum of non-thermal (purely synchrotron and thermal (bremsstrahlung components is applied to fit the integrated radio spectrum of this SNR. The contribution of thermal component to the total volume emissivity at $1 mathrm{GHz}$ is estimated to be $approx37 \\%$. The ambient density is also estimated to be $napprox 9 mathrm{cm}^{-3}$ for $mathrm{T}=10^{4} mathrm{K}$. Again we obtained a relatively significant presence of thermal emission at radio frequencies from the SNR, which can support interaction between SNR HB 3 and adjacent molecular cloud associated with the mbox{H,{sc ii}} region W3. Our model estimates for thermal component contribution to total volume emissivity at $1 mathrm{GHz}$ and ambient density are similar to those obtained earlier ($approx40 \\%$, $approx10 mathrm{cm^{-3}}$. It is thus obvious that the corrected flux density values do not affect the basic conclusions.

  11. (HbA1c) levels with Iinsulin resistance in obese children.

    African Journals Online (AJOL)

    Objectives: We investigated the relationship between insulin resistance reflected by homeostasis model assessment (HOMA-IR) index and serum HbA1c levels of obese children. Material and Methods: This study included 70 obese and 60 normal weight healthy children between the ages of 3 and 15. Anthropometric ...

  12. Predictors of HbA1c levels in patients initiating metformin

    NARCIS (Netherlands)

    Martono, Doti P; Hak, Eelko; Lambers Heerspink, Hiddo; Wilffert, Bob; Denig, Petra

    2016-01-01

    Objective: The aim was to assess demographic and clinical factors as predictors of short (6 months) and long term (18 months) HbA1c levels in diabetes patients initiating metformin treatment. Research design and methods: We conducted a cohort study including type 2 diabetes patients who received

  13. Laserlike Vibrational Instability in Rectifying Molecular Conductors

    DEFF Research Database (Denmark)

    Lu, Jing Tao; Hedegård, Per; Brandbyge, Mads

    2011-01-01

    We study the damping of molecular vibrations due to electron-hole pair excitations in donor-acceptor (D-A) type molecular rectifiers. At finite voltage additional nonequilibrium electron-hole pair excitations involving both electrodes become possible, and contribute to the stimulated emission....... We investigate the effect in realistic molecular rectifier structures using first-principles calculations....

  14. Cross-sectional comparison of point-of-care with laboratory HbA1c in detecting diabetes in real-world remote Aboriginal settings

    Science.gov (United States)

    Marley, Julia V; Oh, May S; Hadgraft, Nyssa; Singleton, Sally; Isaacs, Kim; Atkinson, David

    2015-01-01

    Objectives To determine if point-of-care (POC) glycated haemoglobin (HbA1c) is sufficiently accurate in real-world remote settings to predict or exclude the diagnosis of diabetes based on laboratory HbA1c measurements. Design Cross-sectional study comparing POC capillary HbA1c results with corresponding venous HbA1c levels measured in a reference laboratory. Participants Aboriginal patients ≥15 years old who were due for diabetes screening at the participating clinics were invited to participate. Two hundred and fifty-five Aboriginal participants were enrolled and 241 were included in the analysis. Setting 6 primary healthcare sites in the remote Kimberley region of Western Australia from September 2011 to November 2013. Main outcome measures Concordance and mean differences between POC capillary blood HbA1c measurement and laboratory measurement of venous blood HbA1c level; POC capillary blood HbA1c equivalence value for screening for diabetes or a high risk of developing diabetes; sensitivity, specificity and positive-predictive value for diagnosing and screening for diabetes; barriers to conducting POC testing. Results Concordance between POC and laboratory results was good (ρ=0.88, pHbA1c measurements ≥6.5%, 48 mmol/mol had a specificity of 98.2% and sensitivity of 73.7% for laboratory measurements ≥6.5%. The POC equivalence value for screening for diabetes or a high risk of developing diabetes was ≥5.7%, 39 mmol/mol (sensitivity, 91%; specificity, 76.7% for laboratory measurements ≥6.0%, 42 mmol/mol). Staff trained by other clinic staff ‘on the job’ performed as well as people with formal accredited training. Staff reported difficulty in maintaining formal accreditation. Conclusions POC HbA1c testing is sufficiently accurate to be a useful component in screening for, and diagnosing, diabetes in remote communities. Limited local training is adequate to produce results comparable to laboratory results and accreditation processes need to

  15. Peri-conceptional HbA1c and risk of serious adverse pregnancy outcome in 933 women with type 1 diabetes

    DEFF Research Database (Denmark)

    Jensen, Dorte M; Korsholm, Lars; Ovesen, Per

    2009-01-01

    Objectives : To study the association between peri-conceptional HbA1c and serious adverse pregnancy outcome (congenital malformations and perinatal mortality). Methods: Prospective data collection in 933 singleton pregnancies complicated by type 1 diabetes. Results: The risk of serious adverse ou...... malformation rate increased significantly at HbA1c above 10.4% whereas perinatal mortality was increased even at Hba1c below 6.9%. Conclusions: These results support recent guidelines of pre-conceptional HbA1c levels below 7% in women with type 1 diabetes....

  16. Comparison of a point-of-care analyser for the determination of HbA1c with HPLC method.

    Science.gov (United States)

    Grant, D A; Dunseath, G J; Churm, R; Luzio, S D

    2017-08-01

    As the use of Point of Care Testing (POCT) devices for measurement of glycated haemoglobin (HbA1c) increases, it is imperative to determine how their performance compares to laboratory methods. This study compared the performance of the automated Quo-Test POCT device (EKF Diagnostics), which uses boronate fluorescence quenching technology, with a laboratory based High Performance Liquid Chromatography (HPLC) method (Biorad D10) for measurement of HbA1c. Whole blood EDTA samples from subjects (n=100) with and without diabetes were assayed using a BioRad D10 and a Quo-Test analyser. Intra-assay variation was determined by measuring six HbA1c samples in triplicate and inter-assay variation was determined by assaying four samples on 4 days. Stability was determined by assaying three samples stored at -20 °C for 14 and 28 days post collection. Median (IQR) HbA1c was 60 (44.0-71.2) mmol/mol (7.6 (6.17-8.66) %) and 62 (45.0-69.0) mmol/mol (7.8 (6.27-8.46) %) for D10 and Quo-Test, respectively, with very good agreement (R 2 =0.969, Pglucose intolerance (IGT and T2DM) and 100% for diagnosis of T2DM. Good agreement between the D10 and Quo-Test was seen across a wide HbA1c range. The Quo-Test POCT device provided similar performance to a laboratory based HPLC method.

  17. Extension arm facilitated pegylation of alphaalpha-hemoglobin with modifications targeted exclusively to amino groups: functional and structural advantages of free Cys-93(beta) in the PEG-Hb adduct.

    Science.gov (United States)

    Li, Dongxia; Hu, Tao; Manjula, Belur N; Acharya, Seetharama A

    2009-11-01

    Cys-93(beta) of hemoglobin (Hb) was reversibly protected as a mixed disulfide with thiopyridine during extension arm facilitated (EAF) PEGylation and its influence on the structural and functional properties of the EAF-PEG-Hb has been investigated. Avoiding PEGylation of Cys-93(beta) in the EAF-PEG-Hb lowers the level of perturbation of heme pocket, alpha1beta2 interface, autoxidation, heme loss, and the O(2) affinity, as compared to the EAF-PEG-Hb with PEGylation of Cys-93(beta).The structural and functional advantages of reversible protection of Cys-93(beta) during EAF PEGylation of oxy-Hb has been compared with Euro PEG-Hb generated by EAF PEGylation of deoxy Hb where Cys-93(beta) is free in the final product. The alphaalpha-fumaryl cross-linking and EAF PEGylation targeted exclusively to Lys residues has been combined together for generation of second-generation EAF-PEG-Hb with lower oxygen affinity. The PEG chains engineered on Lys as well as PEGylation of Cys-93(beta) independently contribute to the stabilization of oxy conformation of Hb and hence increase the oxygen affinity of Hb. However, oxygen affinity of the EAF-PEG-alphaalpha-Hb is more sensitive to the presence of PEGylation on Cys-93(beta) than that of the EAF-PEG-Hb. The present modified EAF PEGylation platform is expected to facilitate the design of novel versions of the EAF-PEG-Hbs that can now integrate the advantages of avoiding PEGylation of Cys-93(beta).

  18. One Drop | Mobile on iPhone and Apple Watch: An Evaluation of HbA1c Improvement Associated With Tracking Self-Care.

    Science.gov (United States)

    Osborn, Chandra Y; van Ginkel, Joost R; Marrero, David G; Rodbard, David; Huddleston, Brian; Dachis, Jeff

    2017-11-29

    The One Drop | Mobile app supports manual and passive (via HealthKit and One Drop's glucose meter) tracking of self-care and glycated hemoglobin A 1c (HbA 1c ). We assessed the HbA 1c change of a sample of people with type 1 diabetes (T1D) or type 2 diabetes (T2D) using the One Drop | Mobile app on iPhone and Apple Watch, and tested relationships between self-care tracking with the app and HbA 1c change. In June 2017, we identified people with diabetes using the One Drop | Mobile app on iPhone and Apple Watch who entered two HbA 1c measurements in the app 60 to 365 days apart. We assessed the relationship between using the app and HbA 1c change. Users had T1D (n=65) or T2D (n=191), were 22.7% (58/219) female, with diabetes for a mean 8.34 (SD 8.79) years, and tracked a mean 2176.35 (SD 3430.23) self-care activities between HbA 1c entries. There was a significant 1.36% or 14.9 mmol/mol HbA 1c reduction (F=62.60, PApple Watch may favorably impact glycemic control. ©Chandra Y Osborn, Joost R van Ginkel, David G Marrero, David Rodbard, Brian Huddleston, Jeff Dachis. Originally published in JMIR Mhealth and Uhealth (http://mhealth.jmir.org), 29.11.2017.

  19. Haemoglobin Fontainebleau (HBA2: c. 64G>C) in Oman: molecular and haematological characteristics and interaction with various haemoglobinopathies.

    Science.gov (United States)

    Daar, Shahina; Al Zadjali, Shoaib; Alkindi, Salam; Wali, Yasser; Al-Rawas, Abdulhakeem; Al-Haddabi, Humood; Al-Riyami, Arwa Z

    2018-04-01

    To describe the laboratory features of haemoglobin Fontainebleau (Hb FB) and its interactions with various α and β globin gene mutations in the Omani population. Over a period of 10 years, a total of 94 blood samples were suspected to have an α variant on HPLC at the Sultan Qaboos University Hospital, Muscat, Oman. Molecular testing was performed using PCR based techniques to define the variant and to analyse other interacting mutations in either α or β globin genes. Of 94 subjects, molecular analysis confirmed the Hb FB variant in 55 samples (38 non-cord and 17 cord blood). A total of 36/38 non-cord samples were heterozygous for the variant, while all 17 cord blood samples were heterozygotes. A total of 43/55 individuals had a concomitant α and/or β globin gene mutation. Hb FB is the the most common α variant in the Omani population. We report the different HPLC profiles of this variant that we observed, with and without other haemoglobinopathies in non-cord and cord blood samples. This is the first report describing the HPLC profiles of this α globin chain variant on 1 year follow-up testing of cord blood samples. With careful analysis by HPLC, it is possible not only to identify Hb FB but also to predict any concomitant α and/or β globin gene mutations. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  20. A new approach for the carbon monoxide (CO) exposure diagnosis: measurement of total CO in human blood versus carboxyhemoglobin (HbCO).

    Science.gov (United States)

    Varlet, Vincent; De Croutte, Emma Lagroy; Augsburger, Marc; Mangin, Patrice

    2013-07-01

    The aim of the study is to present the application of a headspace-gas chromatography-mass spectrometry (HS-GC-MS) method for the determination of the carbon monoxide (CO) blood concentration and to compare it with carboxyhemoglobin (HbCO) saturation. In postmortem cases, the HbCO measured by spectrophotometry frequently leads to inaccurate results due to inadequate samples or analyses. The true role of CO intoxication in the death of a person could be misclassified. The estimation of HbCO from HS-GC-MS CO measurements provides helpful information by determining the total CO levels (CO linked to hemoglobin (HbCO) and CO dissociated from hemoglobin). The CO concentrations were converted in HbCO saturation levels to define cutoff blood CO values. CO limits were defined as less than 1 μmol/mL for living persons, less than 1.5 μmol/mL for dead persons without CO exposure, and greater than 3 μmol/mL for dead persons with clear CO poisoning. © 2013 American Academy of Forensic Sciences.