HbA1c in relation to incident diabetes and diabetes-related complications in non-diabetic adults at baseline.

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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.

HbA1c levels in individuals heterozygous for hemoglobin variants.

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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.

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

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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.

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

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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

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

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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.

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

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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.

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

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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.

A novel double heterozygous Hb Fontainebleau/HbD Punjab hemoglobinopathy.

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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.

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

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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.

Trypanosoma brucei gambiense group 1 is distinguished by a unique amino acid substitution in the HpHb receptor implicated in human serum resistance.

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Rebecca E Symula

Full Text Available Trypanosoma brucei rhodesiense (Tbr and T. b. gambiense (Tbg, causative agents of Human African Trypanosomiasis (sleeping sickness in Africa, have evolved alternative mechanisms of resisting the activity of trypanosome lytic factors (TLFs, components of innate immunity in human serum that protect against infection by other African trypanosomes. In Tbr, lytic activity is suppressed by the Tbr-specific serum-resistance associated (SRA protein. The mechanism in Tbg is less well understood but has been hypothesized to involve altered activity and expression of haptoglobin haemoglobin receptor (HpHbR. HpHbR has been shown to facilitate internalization of TLF-1 in T.b. brucei (Tbb, a member of the T. brucei species complex that is susceptible to human serum. By evaluating the genetic variability of HpHbR in a comprehensive geographical and taxonomic context, we show that a single substitution that replaces leucine with serine at position 210 is conserved in the most widespread form of Tbg (Tbg group 1 and not found in related taxa, which are either human serum susceptible (Tbb or known to resist lysis via an alternative mechanism (Tbr and Tbg group 2. We hypothesize that this single substitution contributes to reduced uptake of TLF and thus may play a key role in conferring serum resistance to Tbg group 1. In contrast, similarity in HpHbR sequence among isolates of Tbg group 2 and Tbb/Tbr provides further evidence that human serum resistance in Tbg group 2 is likely independent of HpHbR function.

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

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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.

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

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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.

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

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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.

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

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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.

ROLE OF STEM CELL FACTOR IN THE REACTIVATION OF HUMAN FETAL HEMOGLOBIN

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Ugo Testa

2009-06-01

Full Text Available

In humans the switch from fetal to adult  hemoglobin (HbF→ HbA takes place in the perinatal and postnatal period, determining the progressive replacement of HbF with HbA synthesis ( i.e., the relative HbF content in red blood cells decreases from 80-90% to <1%. In spite of more than twenty years of intensive investigations on this classic model, the molecular mechanisms regulating the Hb switching, as well as HbF synthesis in adults, has been only in part elucidated. In adult life, the residual HbF, restricted to F cell compartment, may be reactivated up to 10-20% of total Hb synthesis in various conditions associated with “stress erythropoiesis”: this reactivation represented until now an interesting model of partial Hb switch reverse with important therapeutic implications in patients with hemoglobinopathies, and particularly in -thalassemia.
In vitro and in vivo models have led to the identification of several chemical compounds able to reactivate HbF synthesis in adult erythroid cells. Although the impact of these HbF inducers, including hypomethylating agents, histone deacetylase inhibitors and hydroxyurea, was clear on the natural history of sickle cell anemia, the benefit on the clinical course of -thalassemia was only limited: particularly, the toxicity and the modest increase in γ-globin reactivation indicated the need for improved agents able to induce higher levels of HbF.
In the present review we describe the biologic properties of Stem Cell Factor (SCF, a cytokine sustaining the survival and proliferation of erythroid cells, that at pharmacological doses acts as a potent stimulator of HbF synthesis in adult erythroid cells.

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

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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.

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

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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.

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

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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.

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.

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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.

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

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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...

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

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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.

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

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

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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

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...

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

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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.

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

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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/.

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

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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.

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

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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.

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

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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.

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

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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.

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.

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

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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.

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

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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.

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

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. 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. 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 Gastric cancer cell invasion obviously increased in wt-HB-EGF-expressing cells, but invasion in HB-EGF-mC-expressing cells showed a slight increase compared with control cells. Moreover, wt-HB-EGF overexpression increased the effectiveness of wound healing, but had no significant effect in HB-EGF-mC-expressing cells. 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

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.

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.

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

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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.

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.

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

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. 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. 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 < 0.01). The growth of wt-HB-EGF- and HB-EGF-mC-expressing cells significantly increased compared with control cells, but the growth of HB-EGF-mC-expressing cells was significantly decreased compared with wt-HB-EGF-expressing cells. Gastric cancer cell invasion obviously increased in wt-HB-EGF-expressing cells, but invasion in HB-EGF-mC-expressing cells showed a slight increase compared with control cells. Moreover, wt-HB-EGF overexpression increased the effectiveness of wound healing, but had no significant effect in HB-EGF-mC-expressing cells. Both the function of HB-EGF as an EGFR ligand and a novel signal for

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

Science.gov (United States)

2012-01-01

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 HB-EGF- and HB-EGF-mC-expressing cells significantly increased compared with control cells, but the growth of HB-EGF-mC-expressing cells was significantly decreased compared with wt-HB-EGF-expressing cells. Gastric cancer cell invasion obviously increased in wt-HB-EGF-expressing cells, but invasion in HB-EGF-mC-expressing cells showed a slight increase compared with control cells. Moreover, wt-HB-EGF overexpression increased the effectiveness of wound healing, but had no significant effect in HB-EGF-mC-expressing cells. Conclusions Both the function of HB-EGF as an EGFR ligand

Ethnic dependent differences in diagnostic accuracy of glycated hemoglobin (HbA1c) in Canadian adults.

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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.

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).

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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.

Can HbA1c be Used to Screen for Glucose Abnormalities Among Adults with Severe Mental Illness?

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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.

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

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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.

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

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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.

Association of plasma PCB levels and HbA1c concentration in Iran.

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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.

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.

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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.

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

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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.

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

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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.

Heme orientational disorder in human adult hemoglobin reconstituted with a ring fluorinated heme and its functional consequences

International Nuclear Information System (INIS)

Nagao, Satoshi; Hirai, Yueki; Kawano, Shin; Imai, Kiyohiro; Suzuki, Akihiro; Yamamoto, Yasuhiko

2007-01-01

A ring fluorinated heme, 13,17-bis(2-carboxylatoethyl)-3,8-diethyl-2-fluoro-7,12, 18-trimethyl-porphyrin-atoiron(III), has been incorporated into human adult hemoglobin (Hb A). The heme orientational disorder in the individual subunits of the protein has been readily characterized using 19 F NMR and the O 2 binding properties of the protein have been evaluated through the oxygen equilibrium analysis. The equilibrated orientations of hemes in α- and β- subunits of the reconstituted protein were found to be almost completely opposite to each other, and hence were largely different from those of the native and the previously reported reconstituted proteins [T. Jue, G.N. La Mar, Heme orientational heterogeneity in deuterohemin-reconstituted horse and human hemoglobin characterized by proton nuclear magnetic resonance spectroscopy, Biochem. Biophys. Res. Commun. 119 (1984) 640-645]. Despite the large difference in the degree of the heme orientational disorder in the subunits of the proteins, the O 2 affinity and the cooperativity of the protein reconstituted with 2-MF were similar to those of the proteins reconstituted with a series of hemes chemically modified at the heme 3- and 8-positions [K. Kawabe, K. Imaizumi, Z. Yoshida, K. Imai, I. Tyuma, Studies on reconstituted myoglobins and hemoglobins II. Role of the heme side chains in the oxygenation of hemoglobin, J. Biochem. 92 (1982) 1713-1722], whose O 2 affinity and cooperativity were higher and lower, respectively, relative to those of native protein. These results indicated that the heme orientational disorder could exert little effect, if any, on the O 2 affinity properties of Hb A. This finding provides new insights into structure-function relationship of Hb A

HbA1c monitoring interval in patients on treatment for stable type 2 diabetes. A ten-year retrospective, open cohort study.

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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.

HbA1c Levels among Primary Healthcare Patients with Type 2 Diabetes Mellitus in Oman

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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.

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

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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.

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

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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.

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

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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

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

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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.

C-Reactive Protein and Gamma-Glutamyltransferase Concentrations in Relation to the Prevalence of Type 2 Diabetes Diagnosed by Glucose or HbA1c Criteria in Chinese Adults in Qingdao, China

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J. Ren

2010-01-01

Full Text Available Aims. To investigate the association of C-reactive protein (CRP and gamma glutamyltransferase (GGT concentrations with newly diagnosed diabetes defined by either glucose or HbA1c criteria in Chinese adults. Methods. A population-based cross-sectional study was conducted in 2006. Data from 1167 men and 1607 women aged 35–74 years were analyzed. Diabetes was defined according to either glucose or HbA1c criteria alone. Results. Compared with nondiabetes, multivariate-adjusted OR (95%CI was 1.13 (0.90,1.42 in men and 1.21 (1.00,1.45 in women for CRP and 1.42 (1.18,1.72 and 1.57 (1.31,1.87 for GGT, respectively. Neither CRP nor GGT was associated with the presence of diabetes defined by the HbA1c criterion. Conclusions. The effect of elevated CRP on diabetes defined by the glucose criterion was mediated through obesity, but elevated GGT was an independent risk factor for diabetes in this Chinese population. None of the two was, however, associated with the elevated HbA1c concentrations.

Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is increased in osteoarthritis and regulates chondrocyte catabolic and anabolic activities

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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

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

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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

HbA1c levels as a function of emotional regulation and emotional intelligence in patients with type 2 diabetes.

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Coccaro, Emil F; Drossos, Tina; Phillipson, Louis

2016-10-01

Understanding the role of emotion in glycemic control may be critical for the long-term treatment of patients with type 2 diabetes (T2D). In this study we investigated the relationship between measures of emotional regulation and emotional intelligence and HbA1c levels in adult patients with T2 diabetes. 100 adult patients with T2 diabetes completed assessments of emotional regulation (i.e., affect intensity/lability) and emotional intelligence and were then correlated with HbA1c levels with several relevant covariates. HbA1c levels were significantly associated with affect intensity (AI: r=.24, p=.018) and with emotional intelligence (EI: r=-.29, p=.004), but not affect lability. These results were the same even after adding income, state depression scores, insulin-dependent status, serum cholesterol, diabetes literacy and self-care as covariates (AI: β=.33, p=.001; EI: β=-.31, p=.002). Diabetes self-care, but not diabetes literacy, was also associated with HbA1c levels (β=-.29, p=.003). These data suggest that aspects of emotional regulation and emotional intelligence play a role in glycemic control in adult patients with T2 diabetes and do so even in the context of several variables relevant to diabetes. If so, interventions that can reduce affect intensity and/or increase emotional intelligence may represent a new strategy in the glycemic control of adult patients with T2 diabetes. Copyright © 2016 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.

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

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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.

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.

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

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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

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

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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.

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

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

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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.

Dietary pattern trajectories during 15 years of follow-up and HbA1c, insulin resistance and diabetes prevalence among Chinese adults.

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Batis, Carolina; Mendez, Michelle A; Sotres-Alvarez, Daniela; Gordon-Larsen, Penny; Popkin, Barry

2014-08-01

Most research on dietary patterns and health outcomes does not include longitudinal exposure data. We used an innovative technique to capture dietary pattern trajectories and their association with haemoglobin A1c (HbA1c), homeostasis model of insulin resistance (HOMA-IR) and prevalence of newly diagnosed diabetes. We included 4096 adults with 3-6 waves of diet data (1991-2006) and biomarkers measured in 2009 from the China Health and Nutrition Survey. Diet was assessed with three 24-h recalls and a household food inventory. We used a dietary pattern previously identified with reduced rank regression that positively predicted diabetes in 2006 (high in wheat products and soy milk and low in rice, legumes, poultry, eggs and fish). We estimated a score for this dietary pattern for each subject at each wave. Using latent class trajectory analysis, we grouped subjects with similar dietary pattern score trajectories over time into five classes. Three trajectory classes were stable over time, and in two classes the diet became unhealthier over time (upward trend in dietary pattern score). Among two classes with similar scores in 2006, the one with the lower (healthier) initial score had an HbA1c 1.64% lower (-1.64 (95% CI -3.17 to -0.11)) and non-significantly a HOMA-IR 6.47% lower (-6.47 (-17.37 to 4.42)) and lower odds of diabetes (0.86 (0.44 to 1.67)). Our findings suggest that dietary pattern trajectories with healthier scores longitudinally had a lower HbA1c compared with those with unhealthier scores, even when the trajectories had similar scores in the end point. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Beyond HbA1c.

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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

Intracapillary HbO2 saturations in murine tumours and human tumour xenografts measured by cryospectrophotometry: relationship to tumour volume, tumour pH and fraction of radiobiologically hypoxic cells.

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Rofstad, E K; Fenton, B M; Sutherland, R M

1988-05-01

Frequency distributions for intracapillary HbO2 saturation were determined for two murine tumour lines (KHT, RIF-1) and two human ovarian carcinoma xenograft lines (MLS, OWI) using a cryospectrophotometric method. The aim was to search for possible relationships between HbO2 saturation status and tumour volume, tumour pH and fraction of radiobiologically hypoxic cells. Tumour pH was measured by 31P NMR spectroscopy. Hypoxic fractions were determined from cell survival curves for tumours irradiated in vivo and assayed in vitro. Tumours in the volume range 100-4000 mm3 were studied and the majority of the vessels were found to have HbO2 saturations below 10%. The volume-dependence of the HbO2 frequency distributions differed significantly among the four tumour lines; HbO2 saturation status decreased with increasing tumour volume for the KHT, RIF-1 and MLS lines and was independent of tumour volume for the OWI line. The data indicated that the rate of decrease in HbO2 saturation status during tumour growth was related to the rate of development of necrosis. The volume-dependence of tumour pH was very similar to that of the HbO2 saturation status for all tumour lines. Significant correlations were therefore found between HbO2 saturation status and tumour pH, both within tumour lines and across the four tumour lines, reflecting that the volume-dependence of both parameters probably was a compulsory consequence of reduced oxygen supply conditions during tumour growth. Hypoxic fraction increased during tumour growth for the KHT, RIF-1 and MLS lines and was volume-independent for the OWI line, suggesting a relationship between HbO2 saturation status and hypoxic fraction within tumour lines. However, there was no correlation between these two parameters across the four tumour lines, indicating that the hypoxic fraction of a tumour is not determined only by the oxygen supply conditions; other parameters may also be important, e.g. oxygen diffusivity, rate of oxygen

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

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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.

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

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.

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.

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.

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.

Both the frequency of HbA1c testing and the frequency of self-monitoring of blood glucose predict metabolic control: A multicentre analysis of 15 199 adult type 1 diabetes patients from Germany and Austria.

Science.gov (United States)

Schwandt, A; Best, F; Biester, T; Grünerbel, A; Kopp, F; Krakow, D; Laimer, M; Wagner, C; Holl, R W

2017-10-01

The objective of this study was to examine the association between metabolic control and frequency of haemoglobin A 1c (HbA 1c ) measurements and of self-monitoring of blood glucose, as well as the interaction of both. Data of 15 199 adult type 1 diabetes patients registered in a standardized electronic health record (DPV) were included. To model the association between metabolic control and frequency of HbA 1c testing or of self-monitoring of blood glucose, multiple hierarchic regression models with adjustment for confounders were fitted. Tukey-Kramer test was used to adjust P values for multiple comparisons. Vuong test was used to compare non-nested models. The baseline variables of the study population were median age 19.9 [Q1; Q3: 18.4; 32.2] years and diabetes duration 10.4 [6.8; 15.7] years. Haemoglobin A 1c was 60.4 [51.5; 72.5] mmol/mol. Frequency of HbA 1c testing was 8.0 [5.0; 9.0] within 2 years, and daily self-monitoring of blood glucose frequency was 5.0 [4.0; 6.0]. After adjustment, a U-shaped association between metabolic control and frequency of HbA 1c testing was observed with lowest HbA 1c levels in the 3-monthly HbA 1c testing group. There was an inverse relationship between self-monitoring of blood glucose and HbA 1c with lower HbA 1c associated with highest frequency of testing (>6 daily measurements). Quarterly HbA 1c testing and frequent self-monitoring of blood glucose were associated with best metabolic control. The adjusted Vuong Z statistic suggests that metabolic control might be better explained by HbA 1c testing compared to self-monitoring of blood glucose (P < .0001). This research reveals the importance of quarterly clinical HbA 1c monitoring together with frequent self-monitoring of blood glucose in diabetes management to reach and maintain target HbA 1c . Copyright © 2017 John Wiley & Sons, Ltd.

[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.

Socioeconomic inequality in Hepatitis B vaccination of rural adults in China.

Science.gov (United States)

Zhu, Dawei; Guo, Na; Wang, Jian; Nicholas, Stephen; Wang, Zhen; Zhang, Guojie; Shi, Luwen; Wangen, Knut Reidar

2018-02-01

Hepatitis B (HB) vaccination is the most effective way to prevent HB virus infection. While measures taken to control the prevalence of HB have achieved significant results, HB prevalence in rural China among adults remains problematic. This study sheds new light on the determinants of HB vaccine uptake and its inequality according to socioeconomic status in rural areas of China. We interviewed 22,283 adults, aged 18-59 years, from 8444 households, in 48 villages from 8 provinces. Vaccination status was modeled by using two logistic models: whether take at least one HB vaccine and whether to complete the entire vaccination regime. The Erreygers' concentration index ([Formula: see text]) was used to quantify the degree of inequality and the decomposition approach was used to uncover the determinants of inequality in vaccine uptake. We found that the coverage rate of HB vaccination is 20.2%, and the completion rate is 16.0%. The [Formula: see text] of at least one dose (0.081) and three doses (0.076) revealed a substantial pro-rich inequality. Income contributed the largest percentage to HB vaccination inequalities (52.17% for at least one dose and 52.03% for complete vaccinations). HB awareness was another important cause of inequality in HB vaccination (around 30%). These results imply that rich had a greater tendency to vaccinate and inequality favouring the rich was almost equal for the complete three doses. While the factors associated with HB vaccination uptake and inequalities were multifaceted, income status and HB awareness were the main barriers for the poor to take HB vaccine by adults in rural China.

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.

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.

Differential sensitivity of Chironomus and human hemoglobin to gamma radiation

Energy Technology Data Exchange (ETDEWEB)

Gaikwad, Pallavi S. [Stress Biology Research Laboratory, Department of Zoology, Savitribai Phule University, Pune, 411007 (India); Molecular Biology Division, Bhabha Atomic Research Centre, Trombay, Mumbai, 400085 (India); Panicker, Lata [Solid State Physics Division, Bhabha Atomic Research Centre, Trombay, Mumbai, 400085 (India); Mohole, Madhura; Sawant, Sangeeta [Bioinformatics Center, Savitribai Phule Pune University, Pune, 411007 (India); Mukhopadhyaya, Rita [Molecular Biology Division, Bhabha Atomic Research Centre, Trombay, Mumbai, 400085 (India); Nath, Bimalendu B., E-mail: bbnath@gmail.com [Stress Biology Research Laboratory, Department of Zoology, Savitribai Phule University, Pune, 411007 (India)

2016-08-05

Chironomus ramosus is known to tolerate high doses of gamma radiation exposure. Larvae of this insect possess more than 95% of hemoglobin (Hb) in its circulatory hemolymph. This is a comparative study to see effect of gamma radiation on Hb of Chironomus and humans, two evolutionarily diverse organisms one having extracellular and the other intracellular Hb respectively. Stability and integrity of Chironomus and human Hb to gamma radiation was compared using biophysical techniques like Dynamic Light Scattering (DLS), UV-visible spectroscopy, fluorescence spectrometry and CD spectroscopy after exposure of whole larvae, larval hemolymph, human peripheral blood, purified Chironomus and human Hb. Sequence- and structure-based bioinformatics methods were used to analyze the sequence and structural similarities or differences in the heme pockets of respective Hbs. Resistivity of Chironomus Hb to gamma radiation is remarkably higher than human Hb. Human Hb exhibited loss of heme iron at a relatively low dose of gamma radiation exposure as compared to Chironomus Hb. Unlike human Hb, the heme pocket of Chironomus Hb is rich in aromatic amino acids. Higher hydophobicity around heme pocket confers stability of Chironomus Hb compared to human Hb. Previously reported gamma radiation tolerance of Chironomus can be largely attributed to its evolutionarily ancient form of extracellular Hb as evident from the present study. -- Highlights: •Comparison of radiation tolerant Chironomus Hb and radiation sensitive Human Hb. •Amino acid composition of midge and human heme confer differential hydrophobicity. •Heme pocket of evolutionarily ancient midge Hb provide gamma radiation resistivity.

Differential sensitivity of Chironomus and human hemoglobin to gamma radiation

International Nuclear Information System (INIS)

Gaikwad, Pallavi S.; Panicker, Lata; Mohole, Madhura; Sawant, Sangeeta; Mukhopadhyaya, Rita; Nath, Bimalendu B.

2016-01-01

Chironomus ramosus is known to tolerate high doses of gamma radiation exposure. Larvae of this insect possess more than 95% of hemoglobin (Hb) in its circulatory hemolymph. This is a comparative study to see effect of gamma radiation on Hb of Chironomus and humans, two evolutionarily diverse organisms one having extracellular and the other intracellular Hb respectively. Stability and integrity of Chironomus and human Hb to gamma radiation was compared using biophysical techniques like Dynamic Light Scattering (DLS), UV-visible spectroscopy, fluorescence spectrometry and CD spectroscopy after exposure of whole larvae, larval hemolymph, human peripheral blood, purified Chironomus and human Hb. Sequence- and structure-based bioinformatics methods were used to analyze the sequence and structural similarities or differences in the heme pockets of respective Hbs. Resistivity of Chironomus Hb to gamma radiation is remarkably higher than human Hb. Human Hb exhibited loss of heme iron at a relatively low dose of gamma radiation exposure as compared to Chironomus Hb. Unlike human Hb, the heme pocket of Chironomus Hb is rich in aromatic amino acids. Higher hydophobicity around heme pocket confers stability of Chironomus Hb compared to human Hb. Previously reported gamma radiation tolerance of Chironomus can be largely attributed to its evolutionarily ancient form of extracellular Hb as evident from the present study. -- Highlights: •Comparison of radiation tolerant Chironomus Hb and radiation sensitive Human Hb. •Amino acid composition of midge and human heme confer differential hydrophobicity. •Heme pocket of evolutionarily ancient midge Hb provide gamma radiation resistivity.

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.

Updates of the HbVar database of human hemoglobin variants and thalassemia mutations

NARCIS (Netherlands)

B. Giardine (Belinda); J. Borg (Joseph); E. Viennas (Emmanouil); C. Pavlidis (Cristiana); K. Moradkhani (Kamran); P. Joly (Philippe); M. Bartsakoulia (Marina); C. Riemer (Cathy); W. Miller (Webb); G. Tzimas (Giannis); H. Wajcman (Henri); R.C. Hardison (Ross); G.P. Patrinos (George)

2014-01-01

textabstractHbVar (http://globin.bx.psu.edu/hbvar) is one of the oldest and most appreciated locus-specific databases launched in 2001 by a multi-center academic effort to provide timely information on the genomic alterations leading to hemoglobin variants and all types of thalassemia and

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.

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.

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.

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

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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.

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.

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

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.

Cellular senescence of human mammary epithelial cells (HMEC) is associated with an altered MMP-7/HB-EGF signaling and increased formation of elastin-like structures.

Science.gov (United States)

Bertram, Catharina; Hass, Ralf

2009-10-01

The extracellular matrix (ECM) and a complex interplay of cell-to-cell and cell-to-matrix (ECM) interactions provide important platforms to determine cellular senescence and a potentially tumorigenic transformation of normal human mammary epithelial cells (HMEC). An enhanced formation of extracellular filaments, consisting of elastin-like structures, in senescent post-selection HMEC populations was paralleled by a significantly increased expression of its precursor protein tropoelastin and matched with a markedly elevated activity of the cross-linking enzyme family of lysyl oxidases (LOX). RNAi experiments revealed both the ECM metalloproteinase MMP-7 and the growth factor HB-EGF as potential effectors of an increased tropoelastin expression. Moreover, co-localization of MMP-7 and HB-EGF as well as a concomittant downstream signaling via Fra-1 indicated a possible association between the reduced MMP-7 enzyme activity and an impaired HB-EGF processing, resulting in an enhanced tropoelastin synthesis during senescence of HMEC. In agreement with previous work, these findings suggested an important influence of the extracellular proteinase MMP-7 on the aging process of HMEC, affecting both extracellular remodeling as well as intracellular signaling pathways.

Single-Use Disposable Electrochemical Label-Free Immunosensor for Detection of Glycated Hemoglobin (HbA1c Using Differential Pulse Voltammetry (DPV

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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.

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.

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

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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.

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.

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.

Hemodynamic measurements in deep brain tissues of humans by near-infrared time-resolved spectroscopy

Science.gov (United States)

Suzuki, Hiroaki; Oda, Motoki; Yamaki, Etsuko; Suzuki, Toshihiko; Yamashita, Daisuke; Yoshimoto, Kenji; Homma, Shu; Yamashita, Yutaka

2014-03-01

Using near-infrared time-resolved spectroscopy (TRS), we measured the human head in transmittance mode to obtain the optical properties, tissue oxygenation, and hemodynamics of deep brain tissues in 50 healthy adult volunteers. The right ear canal was irradiated with 3-wavelengths of pulsed light (760, 795, and 835nm), and the photons passing through the human head were collected at the left ear canal. Optical signals with sufficient intensity could be obtained from 46 of the 50 volunteers. By analyzing the temporal profiles based on the photon diffusion theory, we successfully obtained absorption coefficients for each wavelength. The levels of oxygenated hemoglobin (HbO2), deoxygenated hemoglobin (Hb), total hemoglobin (tHb), and tissue oxygen saturation (SO2) were then determined by referring to the hemoglobin spectroscopic data. Compared with the SO2 values for the forehead measurements in reflectance mode, the SO2 values of the transmittance measurements of the human head were approximately 10% lower, and tHb values of the transmittance measurements were always lower than those of the forehead reflectance measurements. Moreover, the level of hemoglobin and the SO2 were strongly correlated between the human head measurements in transmittance mode and the forehead measurements in the reflectance mode, respectively. These results demonstrated a potential application of this TRS system in examining deep brain tissues of humans.

Glycated hemoglobin HbA1c, waist circumference, and waist-to-height ratio in overweight and obese adolescents

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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.

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

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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

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

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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

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.

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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.

Current Status of HbA1c Biosensors

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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

Prevalence and phenotype of diabetes and prediabetes using fasting glucose vs HbA1c in a Caribbean population.

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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.

Glycated haemoglobin (HbA1c ) and fasting plasma glucose relationships in sea-level and high-altitude settings.

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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.

Plasma microRNA-451 as a novel hemolytic marker for β0-thalassemia/HbE disease

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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

A new approach for the carbon monoxide (CO) exposure diagnosis: measurement of total CO in human blood versus carboxyhemoglobin (HbCO).

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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.

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

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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.

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.

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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.

Transfusion Associated Peak in Hb HPLC Chromatogram – a Case Report

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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

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.

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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.

Impact of age, BMI and HbA1c levels on the genome-wide DNA methylation and mRNA expression patterns in human adipose tissue and identification of epigenetic biomarkers in blood

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Rönn, Tina; Volkov, Petr; Gillberg, Linn

2015-01-01

Increased age, BMI and HbA1c levels are risk factors for several non-communicable diseases. However, the impact of these factors on the genome-wide DNA methylation pattern in human adipose tissue remains unknown. We analyzed the DNA methylation of ∼480 000 sites in human adipose tissue from 96 ma...

How does CKD affect HbA1c?

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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.

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

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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.

Effects of α-Thalassemia on HbA1c Measurement.

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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.

Survey of lead and CO--Hb in inhabitants in general

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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.

Knowledge and Outcome Measure of HbA1c Testing in Asian Indian Patients with Type 2 Diabetes from a Tertiary Care Center

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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

The optical emission from the supernova remnant HB 3

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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.

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

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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.

Hepatitis B serologic survey and review of immunization records of children, adolescents and adults in Fiji, 2008-2009.

Science.gov (United States)

Tsukakoshi, Tatsuhiko; Samuela, Josaia; Rafai, Eric V; Rabuatoka, Uraia; Honda, Sumihisa; Kamiya, Yasuhiko; Buerano, Corazon C; Morita, Kouichi

2015-03-03

In Fiji, hepatitis B (HB) vaccine was introduced into childhood immunization program in 1989 and has been administered as a pentavalent since 2006. This study aimed to: (i) survey and examine the extent to which HB infection continue to occur in children, adolescents and adults in Fiji, and (ii) determine HB coverage rates and timeliness of vaccine administration to children. Serum samples of children, adolescents and adults (aged 6 months to Fiji's HB vaccine control program is achieving its objectives.

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

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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.

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

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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.

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.

Is insulin the preferred treatment for HbA1c >9%?

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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

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

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.

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

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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.

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

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

Induction of anti-HBs in HB vaccine nonresponders in vivo by hepatitis B surface antigen-pulsed blood dendritic cells.

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Fazle Akbar, Sk Md; Furukawa, Shinya; Yoshida, Osamu; Hiasa, Yoichi; Horiike, Norio; Onji, Morikazu

2007-07-01

Antigen-pulsed dendritic cells (DCs) are now used for treatment of patients with cancers, however, the efficacy of these DCs has never been evaluated for prophylactic purposes. The aim of this study was (1) to prepare hepatitis B surface antigen (HBsAg)-pulsed human blood DCs, (2) to assess immunogenicity of HBsAg-pulsed DCs in vitro and (3) to evaluate the efficacy of HBsAg-pulsed DCs in hepatitis B (HB) vaccine nonresponders. Human peripheral blood DCs were cultured with HBsAg to prepare HBsAg-pulsed DCs. The expression of immunogenic epitopes of HBsAg on HBsAg-pulsed DCs was assessed in vitro. Finally, HBsAg-pulsed DCs were administered, intradermally to six HB vaccine nonresponders and the levels of antibody to HBsAg (anti-HBs) in the sera were assessed. HB vaccine nonresponders did not exhibit features of immediate, early or delayed adverse reactions due to administration of HBsAg-pulsed DCs. Anti-HBs were detected in the sera of all HB vaccine nonresponders within 28 days after administration of HBsAg-pulsed DCs. This study opens a new field of application of antigen-pulsed DCs for prophylactic purposes when adequate levels of protective antibody cannot be induced by traditional vaccination approaches.

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.

Hair cortisol concentration and glycated hemoglobin in African American adults.

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Lehrer, H Matthew; Dubois, Susan K; Maslowsky, Julie; Laudenslager, Mark L; Steinhardt, Mary A

2016-10-01

African Americans have higher diabetes prevalence compared to Whites. They also have elevated cortisol levels - indicating possible HPA axis dysregulation - which may raise blood glucose as part of the biological response to physiological and psychosocial stress. Little is known about chronic cortisol levels in African Americans, and even less about the role of chronically elevated cortisol in type 2 diabetes development in this racial group. We used analysis of cortisol in hair to examine associations of long-term (∼3months) cortisol levels with glycated hemoglobin (HbA1c) in a group of African American adults. In exploratory analyses, we also studied the relationship of hair dehydroepiandrosterone (DHEA) with HbA1c. Participants were 61 community-dwelling African American adults (85% female; mean age 54.30 years). The first 3cm of scalp-near hair were analyzed for cortisol and DHEA concentration using enzyme-linked immunoassay analysis. Glycated hemoglobin was assessed, and regression analyses predicting HbA1c from hair cortisol and DHEA were performed in the full sample and in a subsample of participants (n=20) meeting the National Institute of Diabetes and Digestive Kidney Disease (NIDDK) criteria for type 2 diabetes (HbA1c≥6.5%). In the full sample, HbA1c increased with hair cortisol level (β=0.22, p=0.04, f(2)=0.10), independent of age, sex, chronic health conditions, diabetes medication use, exercise, and depressive symptoms. In the subsample of participants with an HbA1c≥6.5%, hair cortisol was also positively related to HbA1c (β=0.45, p=0.04, f(2)=0.32), independent of diabetes medication use. Glycated hemoglobin was unrelated to hair DHEA in both the full sample and HbA1c≥6.5% subsample. Long-term HPA axis dysregulation in the form of elevated hair cortisol is associated with elevated HbA1c in African American adults. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

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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.

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

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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.

Hb TAYBE: clinical and morphological findings IN 43 patients.

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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.

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.

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...

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

Distribution of glycated haemoglobin and its determinants in Korean youth and young adults: a nationwide population-based study.

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Seo, Ji-Young; Hwang, Seung-Sik; Kim, Jae Hyun; Lee, Young Ah; Lee, Seong Yong; Shin, Choong Ho; Yang, Sei Won

2018-01-31

The present study aimed to describe the distribution of and to investigate the factors associated with glycated haemoglobin (HbA1c) values in Korean youth (10-19 years old) and young adults (20-29 years old). Data from the Korea Health and Nutrition Examination Survey (2011-2015) were used. A total of 6,418 participants (male 3,140 [53.2%]) aged 10-29 years were included in the analysis. Percentiles of HbA1c were calculated and HbA1c values were compared according to age, sex, and associated factors. The mean HbA1c values (% [mmol/mol]) were 5.42 ± 0.01 (35.7 ± 0.1) for youths and 5.32 ± 0.01 (34.7 ± 0.1) for young adults (P distribution of HbA1c values in Korean youth and young adults. There were significant differences in the level of HbA1c according to age and sex.

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

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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.

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.

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.

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....

Monomethylfumarate induces γ-globin expression and fetal hemoglobin production in cultured human retinal pigment epithelial (RPE) and erythroid cells, and in intact retina.

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Promsote, Wanwisa; Makala, Levi; Li, Biaoru; Smith, Sylvia B; Singh, Nagendra; Ganapathy, Vadivel; Pace, Betty S; Martin, Pamela M

2014-05-13

Sickle retinopathy (SR) is a major cause of vision loss in sickle cell disease (SCD). There are no strategies to prevent SR and treatments are extremely limited. The present study evaluated (1) the retinal pigment epithelial (RPE) cell as a hemoglobin producer and novel cellular target for fetal hemoglobin (HbF) induction, and (2) monomethylfumarate (MMF) as an HbF-inducing therapy and abrogator of oxidative stress and inflammation in SCD retina. Human globin gene expression was evaluated by RT-quantitative (q)PCR in the human RPE cell line ARPE-19 and in primary RPE cells isolated from Townes humanized SCD mice. γ-Globin promoter activity was monitored in KU812 stable dual luciferase reporter expressing cells treated with 0 to 1000 μM dimethylfumarate, MMF, or hydroxyurea (HU; positive control) by dual luciferase assay. Reverse transcriptase-qPCR, fluorescence-activated cell sorting (FACS), immunofluorescence, and Western blot techniques were used to evaluate γ-globin expression and HbF production in primary human erythroid progenitors, ARPE-19, and normal hemoglobin producing (HbAA) and homozygous β(s) mutation (HbSS) RPE that were treated similarly, and in MMF-injected (1000 μM) HbAA and HbSS retinas. Dihydroethidium labeling and nuclear factor (erythroid-derived 2)-like 2 (Nrf2), IL-1β, and VEGF expression were also analyzed. Retinal pigment epithelial cells express globin genes and synthesize adult and fetal hemoglobin MMF stimulated γ-globin expression and HbF production in cultured RPE and erythroid cells, and in HbSS mouse retina where it also reduced oxidative stress and inflammation. The production of hemoglobin by RPE suggests the potential involvement of this cell type in the etiology of SR. Monomethylfumarate influences multiple parameters consistent with improved retinal health in SCD and may therefore be of therapeutic potential in SR treatment. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

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

A two-step screening, measurement of HbA1c in association with FPG, may be useful in predicting diabetes.

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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.

Have you got any cholesterol? Adults' views of human nutrition

Science.gov (United States)

Schibeci, Renato; Wong, Khoon Yoong

1994-12-01

The general aim of our human nutrition project is to develop a health education model grounded in ‘everyday’ or ‘situated’ cognition (Hennessey, 1993). In 1993, we began pilot work to document adult understanding of human nutrition. We used a HyperCard stack as the basis for a series of interviews with 50 adults (25 university students, and 25 adults from offcampus). The interviews were transcribed and analysed using the NUDIST computer program. A summary of the views of these 50 adults on selected aspects of human nutrition is presented in this paper.

Development of novel antibacterial active, HaCaT biocompatible and biodegradable CA-g-P(3HB-EC biocomposites with caffeic acid as a functional entity

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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.

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

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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.  

Film and the Young Adult Novel.

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Foster, Harold M.

1994-01-01

Discusses films based on young adult novels and why they are often considered failures. Describes various films about young adults and their problems that have proven to be artistic successes. Gives close attention to film versions of S. E. Hinton's novels and of Robert Cormier's "The Chocolate War." (HB)

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

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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...

Design and synthesis of novel sulfonamide-containing bradykinin hB2 receptor antagonists. 1. Synthesis and SAR of alpha,alpha-dimethylglycine sulfonamides.

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Fattori, Daniela; Rossi, Cristina; Fincham, Christopher I; Berettoni, Marco; Calvani, Federico; Catrambone, Fernando; Felicetti, Patrizia; Gensini, Martina; Terracciano, Rosa; Altamura, Maria; Bressan, Alessandro; Giuliani, Sandro; Maggi, Carlo A; Meini, Stefania; Valenti, Claudio; Quartara, Laura

2006-06-15

We recently published the extensive in vivo pharmacological characterization of MEN 16132 (J. Pharmacol. Exp. Ther. 2005, 616-623; Eur. J. Pharmacol. 2005, 528, 7), a member of the sulfonamide-containing human B(2) receptor (hB(2)R) antagonists. Here we report, in detail, how this family of compounds was designed, synthesized, and optimized to provide a group of products with subnanomolar affinity for the hB(2)R and high in vivo potency after topical administration to the respiratory tract. The series was designed on the basis of indications from the X-ray structures of the key structural motifs A and B present in known antagonists and is characterized by the presence of an alpha,alpha-dialkyl amino acid. The first lead (17) of the series was submitted to extensive chemical work to elucidate the structural requirements to increase hB(2) receptor affinity and antagonist potency in bioassays expressing the human B(2) receptor (hB(2)R). The following structural features were selected: a 2,4-dimethylquinoline moiety and a piperazine linker acylated with a basic amino acid. The representative lead compound 68 inhibited the specific binding of [(3)H]BK to hB(2)R with a pKi of 9.4 and antagonized the BK-induced inositolphosphate (IP) accumulation in recombinant cell systems expressing the hB(2)R with a pA(2) of 9.1. Moreover, compound 68 when administered (300 nmol/kg) intratracheally in the anesthetized guinea pig, was able to significantly inhibit BK-induced bronchoconstriction for up to 120 min after its administration, while having a lower and shorter lasting effect on hypotension.

Transcriptional profiling of adult neural stem-like cells from the human brain.

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Cecilie Jonsgar Sandberg

Full Text Available There is a great potential for the development of new cell replacement strategies based on adult human neural stem-like cells. However, little is known about the hierarchy of cells and the unique molecular properties of stem- and progenitor cells of the nervous system. Stem cells from the adult human brain can be propagated and expanded in vitro as free floating neurospheres that are capable of self-renewal and differentiation into all three cell types of the central nervous system. Here we report the first global gene expression study of adult human neural stem-like cells originating from five human subventricular zone biopsies (mean age 42, range 33-60. Compared to adult human brain tissue, we identified 1,189 genes that were significantly up- and down-regulated in adult human neural stem-like cells (1% false discovery rate. We found that adult human neural stem-like cells express stem cell markers and have reduced levels of markers that are typical of the mature cells in the nervous system. We report that the genes being highly expressed in adult human neural stem-like cells are associated with developmental processes and the extracellular region of the cell. The calcium signaling pathway and neuroactive ligand-receptor interactions are enriched among the most differentially regulated genes between adult human neural stem-like cells and adult human brain tissue. We confirmed the expression of 10 of the most up-regulated genes in adult human neural stem-like cells in an additional sample set that included adult human neural stem-like cells (n = 6, foetal human neural stem cells (n = 1 and human brain tissues (n = 12. The NGFR, SLITRK6 and KCNS3 receptors were further investigated by immunofluorescence and shown to be heterogeneously expressed in spheres. These receptors could potentially serve as new markers for the identification and characterisation of neural stem- and progenitor cells or as targets for manipulation of cellular

Real-world Clinical Outcomes Among Patients With Type 2 Diabetes Receiving Canagliflozin at a Specialty Diabetes Clinic: Subgroup Analysis by Baseline HbA1c and Age.

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Johnson, June Felice; Parsa, Rahul; Bailey, Robert A

2017-06-01

Canagliflozin, a sodium glucose co-transporter 2 inhibitor developed for the treatment of type 2 diabetes mellitus (T2DM), has demonstrated effectiveness in patients with T2DM receiving care at a specialty diabetes clinic. We report the outcomes in these patients in subgroups classified by baseline hemoglobin A 1c (HbA 1c ) and age. This subgroup analysis was based on a review of data from the electronic health records of adults with T2DM who were prescribed canagliflozin at a specialty diabetes clinic and who returned for ≥1 follow-up office visit. Mean changes from baseline to the first and second follow-up office visits in HbA 1c , body weight, and systolic and diastolic blood pressure (BP) were calculated in each subgroup classified by baseline HbA 1c (≥7.0%, ≥8.0%, and >9.0%) and age (baseline HbA 1c ≥7.0%, ≥8.0%, and >9.0%, respectively; 396 and 66 patients were aged baseline HbA 1c and age experienced clinically and statistically significant reductions from baseline in HbA 1c , body weight, and systolic BP that were sustained over 2 office visits; diastolic BP was also reduced across baseline HbA 1c and age subgroups. Greater reductions in HbA 1c were seen among the canagliflozin-treated patients with higher baseline HbA 1c and among younger versus older patients. These findings from clinical practice demonstrate real-world effectiveness of canagliflozin in lowering HbA 1c , body weight, and systolic BP among patients with T2DM, regardless of baseline HbA 1c levels or age. Copyright © 2017 Elsevier HS Journals, Inc. All rights reserved.

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

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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

The Import of Abdominal Pain in Adults with Sickle Cell Disorder ...

African Journals Online (AJOL)

crisis in sickle cell patients with abdominal pain and their clinical correlates if any. METHODS: Clinical records of adults with SCD (Hb SS and Hb SC) attending the Haematology Outpatients' Clinic of the Obafemi Awolowo University Teaching Hospitals Complex, Southwest Nigerian, over a ten-year period, were reviewed.

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].

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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.

Posterior transverse interarch discrepancy on HbE β thalassemia patients

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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

Qualitative analysis neurons in the adult human dentate nucleus

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Marić Dušica

2012-01-01

Full Text Available Although many relevant findings regarding to the morphology and cytoarchitectural development of the dentate nucleus have been presented so far, very little qualitative information has been collected on neuronal morphology in the adult human dentate nucleus. The neurons were labelled by Golgi staining from thirty human cerebella, obtained from medico-legal forensic autopsies of adult human bodies and free of significant brain pathology. The human dentate neurons were qualitatively analyzed and these cells were classified into two main classes: the small and the large multipolar neurons. Considering the shape of the cell body, number of the primary dendrites, shape of the dendritic tree and their position within the dentate nucleus, three subclasses of the large multipolar neurons have been recognized. The classification of neurons from the human dentate nucleus has been qualitatively confirmed in fetuses and premature infants. This study represents the first qualitative analysis and classification of the large multipolar neurons in the dentate nucleus of the adult human.

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

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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.

Hemorheological alterations in adults with prediabetes identified by hemoglobin A1c levels.

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Marini, M A; Fiorentino, T V; Andreozzi, F; Mannino, G C; Succurro, E; Sciacqua, A; Perticone, F; Sesti, G

2017-07-01

A link between increased blood viscosity and type 2 diabetes has been previously reported. Herein, we investigated the association of blood viscosity with prediabetes, identified by glycated hemoglobin A1c (HbA1c) according to the new American Diabetes Association criteria, and subclinical atherosclerosis. The study cohort includes 1136 non-diabetic adults submitted to anthropometrical evaluation, an oral glucose tolerance test and ultrasound measurement of carotid intima-media thickness (IMT). Whole blood viscosity was estimated using a validated formula based on hematocrit and total plasma proteins. After adjusting for age, and gender, individuals with HbA1c-defined prediabetes (HbA1c 5.7-6.4% [39-47 mmol/mol]) exhibited significantly higher values of hematocrit, and predicted blood viscosity as compared with controls. Increased levels of IMT were observed in subjects with HbA1c-defined prediabetes in comparison to controls. Predicted blood viscosity was positively correlated with age, waist circumference, blood pressure, cholesterol, triglycerides, fibrinogen, white blood cell, HbA1c, fasting and 2-h post-load glucose levels, fasting insulin, IMT and inversely correlated with HDL and Matsuda index of insulin sensitivity. Of the three glycemic parameters, i.e. HbA1c, fasting and 2-h post-load glucose, only HbA1c showed a significant correlation with predicted blood viscosity (β = 0.054, P = 0.04) in a multivariate regression analysis model including multiple atherosclerosis risk factors. The study shows that individuals with HbA1c-defined prediabetes have increased predicted blood viscosity and IMT. The HbA1c criterion may be helpful to capture individuals with an increased risk of diabetes and cardiovascular disease who may benefit from an intensive lifestyle intervention. Copyright © 2017 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical

HbA1c, fasting plasma glucose and the prediction of diabetes

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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....

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

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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

HbA1c for diagnosis and prognosis of gestational diabetes mellitus.

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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.

Activin receptor subunits in normal and dysfunctional adult human testis

DEFF Research Database (Denmark)

Dias, V; Meachem, S; Rajpert-De Meyts, E

2008-01-01

The cellular sites of activin action and its regulation in the normal and dysfunctional adult human testis are unknown.......The cellular sites of activin action and its regulation in the normal and dysfunctional adult human testis are unknown....

Adult Education & Human Resource Development: Overlapping and Disparate Fields

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Watkins, Karen E.; Marsick, Victoria J.

2014-01-01

Adult education and human resource development as fields of practice and study share some roots in common but have grown in different directions in their histories. Adult education's roots focused initially on citizenship for a democratic society, whereas human resource development's roots are in performance at work. While they have…

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.

Are Ethnic Disparities in HbA1c Levels Explained by Mental Wellbeing? Analysis of Population-Based Data from the Health Survey for England.

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Umeh, Kanayo

2018-02-01

It is unclear how ethnic differences in HbA 1c levels are affected by individual variations in mental wellbeing. Thus, the aim of this study was to assess the extent to which HbA 1c disparities between Caucasian and South Asian adults are mediated by various aspects of positive psychological functioning. Data from the 2014 Health Survey for England was analysed using bootstrapping methods. A total of 3894 UK residents with HbA 1c data were eligible to participate. Mental wellbeing was assessed using the Warwick-Edinburgh Mental Well-being Scale. To reduce bias BMI, blood pressure, diabetes status, and other factors were treated as covariates. Ethnicity directly predicted blood sugar control (unadjusted coefficient -2.15; 95% CI -3.64, -0.67), with Caucasians generating lower average HbA 1c levels (37.68 mmol/mol (5.6%)) compared to South Asians (39.87 mmol/mol (5.8%)). This association was mediated by positive mental wellbeing, specifically concerning perceived vigour (unadjusted effect 0.30; 95% CI 0.13, 0.58): South Asians felt more energetic than Caucasians (unadjusted coefficient -0.32; 95% CI -0.49, -0.16), and greater perceived energy predicted lower HbA 1c levels (unadjusted coefficient -0.92; 95% CI -1.29, -0.55). This mediator effect accounted for just over 14% of the HbA 1c variance and was negated after adjusting for BMI. Caucasian experience better HbA 1c levels compared with their South Asian counterparts. However, this association is partly confounded by individual differences in perceived energy levels, which is implicated in better glycaemic control, and appears to serve a protective function in South Asians.

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.

Germline stem cells and neo-oogenesis in the adult human ovary.

Science.gov (United States)

Liu, Yifei; Wu, Chao; Lyu, Qifeng; Yang, Dongzi; Albertini, David F; Keefe, David L; Liu, Lin

2007-06-01

It remains unclear whether neo-oogenesis occurs in postnatal ovaries of mammals, based on studies in mice. We thought to test whether adult human ovaries contain germline stem cells (GSCs) and undergo neo-oogenesis. Rather than using genetic manipulation which is unethical in humans, we took the approach of analyzing the expression of meiotic marker genes and genes for germ cell proliferation, which are required for neo-oogenesis, in adult human ovaries covering an age range from 28 to 53 years old, compared to testis and fetal ovaries served as positive controls. We show that active meiosis, neo-oogenesis and GSCs are unlikely to exist in normal, adult, human ovaries. No early meiotic-specific or oogenesis-associated mRNAs for SPO11, PRDM9, SCP1, TERT and NOBOX were detectable in adult human ovaries using RT-PCR, compared to fetal ovary and adult testis controls. These findings are further corroborated by the absence of early meiocytes and proliferating germ cells in adult human ovarian cortex probed with markers for meiosis (SCP3), oogonium (OCT3/4, c-KIT), and cell cycle progression (Ki-67, PCNA), in contrast to fetal ovary controls. If postnatal oogenesis is confirmed in mice, then this species would represent an exception to the rule that neo-oogenesis does not occur in adults.

Improving Detection of Prediabetes in Children and Adults: Using Combinations of Blood Glucose Tests

Directory of Open Access Journals (Sweden)

Ike Solomon Okosun

2015-11-01

Full Text Available Aim: To determine combinations of blood glucose tests: oral glucose tolerance (OGT, fasting plasma glucose (FBG and hemoglobin A1C (HbA1C that are associated with highest diagnostic rates of prediabetes in non-diabetic American children and adults.Methods: The 2007-2008 U.S. National Health and Nutrition Examination Surveys data were used for this study. Overall and specific prevalence of prediabetes (defined using OGT+FPG, OGT+HbA1C, HbA1C+FPG and OGT+FPG+HbA1C tests were determined across age, race/ethnicity, sex and BMI categories.Results: FPG+HbA1C test was associated with significantly higher diagnostic rates of prediabetes across age, race/ethnicity and BMI. Estimates of overall prevalence of prediabetes using OGT+FPG, OGT+HbA1C, HbA1C+FPG and OGT+FPG+HbA1C tests were 20.3%, 24.2%, 33% and 34.3%, respectively. Compared to OGT+FPG, the use of HbA1C+FPG test in screening was associated with 44.8%, 135%, 38.6% and 35.9% increased prevalence of prediabetes in non-Hispanic White, non-Hispanic Black, Mexican-American and other racial/ethnic men, respectively. The corresponding values in women were 67.8%, 140%, 37.2% and 42.6%, respectively. Combined use of all blood glucose tests did not improve the overall and gender-specific prediabetes prevalence beyond what was observed using HbA1C+FPG test.Conclusions: HbA1C criteria were associated with higher diagnosis rates of prediabetes than FPG and OGT tests in non-diabetic American children and adults. Using a combination of HbA1C and FPG test in screening for prediabetes reduces intrinsic systematic bias in using just HbA1C testing and offers the benefits of each test. A well-defined HbA1C that takes into consideration race/ethnicity, gender, age and body mass index may improve detection of prediabetes in population and clinical settings.

A near infrared instrument to monitor relative hemoglobin concentrations of human bone tissue in vitro and in vivo

Science.gov (United States)

Aziz, Syed Mahfuzul; Khambatta, Faram; Vaithianathan, Tharshan; Thomas, John C.; Clark, Jillian M.; Marshall, Ruth

2010-04-01

A continuous wave near infrared instrument has been developed to monitor in vivo changes in the hemoglobin concentration of the trabecular compartment of human bone. The transmitter uses only two laser diodes of wavelengths 685 and 830 nm, and the receiver uses a single silicon photodiode operating in the photovoltaic mode. The functioning of the instrument and the depth of penetration of the near infrared signals was determined in vitro using tissue-equivalent phantoms. The instrument achieves a depth of penetration of approximately 2 cm for an optode separation of 4 cm and, therefore, has the capacity to interrogate the trabecular compartment of human bone. The functioning of the instrument was tested in vivo to evaluate the relative oxy-hemoglobin (HbO2) and deoxy-hemoglobin (Hb) concentrations of the proximal tibial bone of apparently healthy, normal weight, adult subjects in response to a 3 min on, 5 min off, vascular occlusion protocol. The traces of the relative Hb and HbO2 concentrations obtained were reproducible in controlled conditions. The instrument is relatively simple and flexible, and offers an inexpensive platform for further studies to obtain normative data for healthy cohorts, and to evaluate disease-specific performance characteristics for cohorts with vasculopathies of bone.

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

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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.

Hb A2 Episkopi - a novel δ-globin chain variant [HBD:c.428C>T] in a family of mixed Cypriot-Lebanese descent.

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Lederer, Carsten W; Pavlou, Eleni; Tanteles, George A; Evangelidou, Paola; Sismani, Carolina; Kolnagou, Annita; Sitarou, Maria; Christou, Soteroulla; Hadjigavriel, Michael; Kleanthous, Marina

2017-06-01

Thalassaemia is a potentially lethal inherited anaemia, caused by reduced or absent synthesis of globin chains. Measurement of the minor adult haemoglobin Hb A 2 , combining α- with δ-globin, is critical for the routine diagnosis of carrier status for α- or β-thalassaemia. Here, we aim to characterize a novel δ-globin variant, Hb A 2 Episkopi, in a single family of mixed Lebanese and Cypriot ancestry with mild hypochromic anaemia and otherwise normal globin genotype, which also presents with a coincidental 0.78-Mb sequence duplication on chromosome 1 (1q44) and developmental abnormalities. Analyses included comprehensive haematological analyses, cation-exchange high-performance liquid chromatography (CE-HPLC), cellulose acetate electrophoresis (CAE), Sanger sequencing and structure-based stability predictions for Hb A 2 Episkopi. The GCT > GTT missense mutation, underlying Hb A 2 Episkopi, HBD:c.428C > T, introduces a cd142 codon change in the mature protein, resulting in reduced normal Hb A 2 amounts and a novel, less abundant Hb A 2 variant (HGVS: HBD:p.A143V), detectable as a delayed peak by CE-HPLC. The latter was in line with structure-based stability predictions, which indicated that the substitution of a marginal, non-helical and non-interface residue, five amino acids from the δ-globin chain carboxy-terminus, was moderately destabilizing. Detection of the new variant depends on the diagnostic set-up and had failed by CAE and on an independent CE-HPLC system, which, in unfavourable circumstances, may lead to misdiagnoses of β-thalassaemia as α-thalassaemia. Given the mixed background of the affected family, the ethnic origin of the mutation is unclear, and this study thus suggests awareness for possible detection of Hb A 2 Episkopi in both the Cypriot and the Lebanese populations.

Hemoglobin A1c and arterial and ventricular stiffness in older adults.

Directory of Open Access Journals (Sweden)

Susan J Zieman

Full Text Available Arterial and ventricular stiffening are characteristics of diabetes and aging which confer significant morbidity and mortality; advanced glycation endproducts (AGE are implicated in this stiffening pathophysiology. We examined the association between HbA(1c, an AGE, with arterial and ventricular stiffness measures in older individuals without diabetes.Baseline HbA(1c was measured in 830 participants free of diabetes defined by fasting glucose or medication use in the Cardiovascular Health Study, a population-based cohort study of adults aged ≥ 65 years. We performed cross-sectional analyses using baseline exam data including echocardiography, ankle and brachial blood pressure measurement, and carotid ultrasonography. We examined the adjusted associations between HbA(1c and multiple arterial and ventricular stiffness measures by linear regression models and compared these results to the association of fasting glucose (FG with like measures.HbA(1c was correlated with fasting and 2-hour postload glucose levels (r = 0.21; p<0.001 for both and positively associated with greater body-mass index and black race. In adjusted models, HbA(1c was not associated with any measure of arterial or ventricular stiffness, including pulse pressure (PP, carotid intima-media thickness, ankle-brachial index, end-arterial elastance, or left ventricular mass (LVM. FG levels were positively associated with systolic, diastolic and PP and LVM.In this sample of older adults without diabetes, HbA(1c was not associated with arterial or ventricular stiffness measures, whereas FG levels were. The role of AGE in arterial and ventricular stiffness in older adults may be better assessed using alternate AGE markers.

Advanced glycation end products, measured in skin, vs. HbA1c in children with type 1 diabetes mellitus.

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Banser, Alena; Naafs, Jolanda C; Hoorweg-Nijman, Jantine Jg; van de Garde, Ewoudt Mw; van der Vorst, Marja Mj

2016-09-01

Advanced glycation end products (AGEs) are considered major contributors to microvascular and macrovascular complications in adult patients with diabetes mellitus. AGEs can be measured non-invasively with skin autofluorescence (sAF). The primary aim was to determine sAF values in children with type 1 diabetes mellitus and to study correlations between sAF values and HbA1c and mean HbA1c over the year prior to measurement In children with type 1 diabetes mellitus, sAF values were measured using the AGE Reader®. Laboratory and anthropometric values were extracted from medical charts. Correlations were studied using Pearson's correlation coefficient. Multivariable linear regression analysis was conducted to evaluate the effect of multiple study parameters on sAF values. The mean sAF value was 1.33 ± 0.36 arbitrary units (AU) in children with type 1 diabetes mellitus (n = 144). sAF values correlated positively with HbA1c measured at the same time (r = 0.485; p 1), mean HbA1c over the year prior to measurement (r = 0.578; p 1), age (r = 0.337; p 1), duration of type 1 diabetes mellitus (r = 0.277; p = 0.001), serum triglycerides (r = 0.399; p 1), and total cholesterol (r = 0.352; p = 0.001). sAF values were significantly higher in patients with non-white skin (1.56 vs. 1.27 AU, respectively, p = 0.001). In children with type 1 diabetes, sAF values correlate strongly with single HbA1c and mean HbA1c, making the non-invasive sAF measurement an interesting alternative to provide information about cumulative hyperglycemic states. To determine the value of sAF measurement in predicting long-term microvascular and macrovascular complications, further prospective follow-up studies are needed. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Abnormal pulmonary function in adults with sickle cell anemia.

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Klings, Elizabeth S; Wyszynski, Diego F; Nolan, Vikki G; Steinberg, Martin H

2006-06-01

Pulmonary complications of sickle cell anemia (Hb-SS) commonly cause morbidity, yet few large studies of pulmonary function tests (PFTs) in this population have been reported. PFTs (spirometry, lung volumes, and diffusion capacity for carbon monoxide [DLCO]) from 310 adults with Hb-SS were analyzed to determine the pattern of pulmonary dysfunction and their association with other systemic complications of sickle cell disease. Raw PFT data were compared with predicted values. Each subject was subclassified into one of five groups: obstructive physiology, restrictive physiology, mixed obstructive/restrictive physiology, isolated low DLCO, or normal. The association between laboratory data of patients with decreased DLCO or restrictive physiology and those of normal subjects was assessed by multivariate linear regression. Normal PFTs were present in only 31 of 310 (10%) patients. Overall, adults with Hb-SS were characterized by decreased total lung capacities (70.2 +/- 14.7% predicted) and DLCO (64.5 +/- 19.9%). The most common PFT patterns were restrictive physiology (74%) and isolated low DLCO (13%). Decreased DLCO was associated with thrombocytosis (p = 0.05), with hepatic dysfunction (elevated alanine aminotransferase; p = 0.07), and a trend toward renal dysfunction (elevated blood urea nitrogen and creatinine; p = 0.05 and 0.07, respectively). Pulmonary function is abnormal in 90% of adult patients with Hb-SS. Common abnormalities include restrictive physiology and decreased DLCO. Decreased DLCO may indicate more severe sickle vasculopathy characterized by impaired hepatic and renal function.

Influencing Pathways to Quality of Life and HbA1c in Patients With Diabetes: A Longitudinal Study That Inform Evidence-Based Practice.

Science.gov (United States)

Hsu, Hui-Chun; Lee, Yau-Jiunn; Wang, Ruey-Hsia

2018-04-01

Determining possible associated factors and the influencing pathways to hemoglobin A1C (HbA1C) levels and quality of life (QoL) will facilitate the development of effective interventions to improve the physical and psychosocial health of patients with type 2 diabetes mellitus (T2DM). To test a hypothesized model that addressed the pathways among personal characteristics, social support, diabetes distress, and self-care behaviors to HbA1C and QoL. A total of 382 adults with T2DM were recruited. Self-reported questionnaires and medical records were used to collect data regarding personal characteristics, diabetes distress, and social support at baseline. The self-care behaviors characters were collected 6 months later, as well as QoL and HbA1C levels 1 year later. The 12-month QoL directly affected 12-month HbA1C levels. The 6-month self-care behaviors directly affected 12-month QoL, and indirectly affected 12-month HbA1C levels through 12-month QoL. Baseline diabetes distress directly affected 12-month QoL. Moreover, baseline diabetes distress indirectly affected 12-month HbA1C levels through 12-month QoL. Baseline social support directly affected baseline diabetes distress and 6-month self-care behaviors. In addition, baseline social support indirectly affected 12-month QoL through baseline diabetes distress. Baseline social support also indirectly affected 12-month QoL through 6-month self-care behaviors. Enhancing QoL is important to improve HbA1C levels. Enhancing self-care behaviors is essential to improve subsequent HbA1C control and QoL. Reducing diabetes distress is crucial to improve subsequent QoL. Improving social support is suggested a favorable strategy to reduce diabetes distress and enhance subsequent self-care behaviors in patients with T2DM. © 2018 Sigma Theta Tau International.

Low fetal hemoglobin percentage is associated with silent brain lesions in adults with homozygous sickle cell disease.

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Calvet, David; Tuilier, Titien; Mélé, Nicolas; Turc, Guillaume; Habibi, Anoosha; Abdallah, Nassim Ait; Majhadi, Loubna; Hemery, François; Edjlali, Myriam; Galacteros, Frédéric; Bartolucci, Pablo

2017-12-12

Silent white matter changes (WMCs) on brain imaging are common in individuals with sickle cell disease (SCD) and are associated with cognitive deficits in children. We investigated the factors predictive of WMCs in adults with homozygous SCD and no history of neurological conditions. Patients were recruited from a cohort of adults with homozygous SCD followed up at an adult sickle cell referral center for which steady-state measurements of biological parameters and magnetic resonance imaging scans of the brain were available. WMCs were rated by consensus, on a validated age-related WMC scale. The prevalence of WMCs was 49% (95% confidence interval [CI], 39%-60%) in the 83 patients without vasculopathy included. In univariable analysis, the patients who had WMCs were more likely to be older ( P = .003) and to have hypertension ( P = .02), a lower mean corpuscular volume ( P = .005), a lower corpuscular hemoglobin concentration ( P = .008), and a lower fetal hemoglobin percentage (%HbF) ( P = .003). In multivariable analysis, only a lower %HbF remained associated with the presence of WMCs (odds ratio [OR] per 1% increase in %HbF, 0.84; 95% CI, 0.72-0.97; P = .021). %HbF was also associated with WMC burden ( P for trend = .007). Multivariable ordinal logistic regression showed an inverse relationship between WMC burden (age-related WMC score divided into 4 strata) and HbF level (OR for 1% increase in %HbF, 0.89; 95% CI, 0.79-0.99; P = .039). Our study suggests that HbF may protect against silent WMCs, decreasing the likelihood of WMCs being present and their severity. It may therefore be beneficial to increase HbF levels in patients with WMCs.

Hb A1c Separation by High Performance Liquid Chromatography in Hemoglobinopathies

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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.

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.

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.

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 ...

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

Nutritional intervention and impact of polyphenol on glycohemoglobin (HbA1c) in non-diabetic and type 2 diabetic subjects: Systematic review and nmeta-analysis.

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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.

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....

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.

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

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.

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.

ROLE OF STEM CELL FACTOR IN THE REACTIVATION OF HUMAN FETAL HEMOGLOBIN

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Marco Gabbianelli

2009-11-01

In vitro and in vivo models have led to the identification of several chemical compounds able to reactivate HbF synthesis in adult erythroid cells. Although the impact of these HbF inducers, including hypomethylating agents, histone deacetylase inhibitors and hydroxyurea, was clear on the natural history of sickle cell anemia, the benefit on the clinical course of -thalassemia was only limited: particularly, the toxicity and the modest increase in γ-globin reactivation indicated the need for improved agents able to induce higher levels of HbF. In the present review we describe the biologic properties of Stem Cell Factor (SCF, a cytokine sustaining the survival and proliferation of erythroid cells, that at pharmacological doses acts as a potent stimulator of HbF synthesis in adult erythroid cells.

Teaching for Visual Literacy: 50 Great Young Adult Films.

Science.gov (United States)

Teasley, Alan B.; Wilder, Ann

1994-01-01

Discusses how films portraying the lives of young adults can serve as the basis for a "viewer response" study of film and filmmaking. Lists and summarizes 50 films found to be suitable for teaching to young adults. Provides criteria by which the films were selected. (HB)

Low fetal hemoglobin percentage is associated with silent brain lesions in adults with homozygous sickle cell disease

OpenAIRE

Calvet, David; Tuilier, Titien; Mélé, Nicolas; Turc, Guillaume; Habibi, Anoosha; Abdallah, Nassim Ait; Majhadi, Loubna; Hemery, François; Edjlali, Myriam; Galacteros, Frédéric; Bartolucci, Pablo

2017-01-01

Low %HbF is independently associated with silent WMCs on brain imaging in adults with SCD.Our results highlight the potential use of therapeutic strategies inducing HbF expression in SCD patients with silent white matter changes.

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.

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

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.

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.

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…

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.

Adult Functional Literacy Curriculum: Effective Strategy for Human ...

African Journals Online (AJOL)

Adult functional literacy curriculum no doubt, is a panacea to human resource development in Nigeria. Government and non-government organizations have roles to play in providing functional education to adults who drop out of school or have no opportunity of attending the formal school system for all round development.

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

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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.

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

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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.

Abnormal Pulmonary Function in Adults with Sickle Cell Anemia

Science.gov (United States)

Klings, Elizabeth S.; Wyszynski, Diego F.; Nolan, Vikki G.; Steinberg, Martin H.

2006-01-01

Rationale: Pulmonary complications of sickle cell anemia (Hb-SS) commonly cause morbidity, yet few large studies of pulmonary function tests (PFTs) in this population have been reported. Objectives: PFTs (spirometry, lung volumes, and diffusion capacity for carbon monoxide [DLCO]) from 310 adults with Hb-SS were analyzed to determine the pattern of pulmonary dysfunction and their association with other systemic complications of sickle cell disease. Methods: Raw PFT data were compared with predicted values. Each subject was subclassified into one of five groups: obstructive physiology, restrictive physiology, mixed obstructive/restrictive physiology, isolated low DLCO, or normal. The association between laboratory data of patients with decreased DLCO or restrictive physiology and those of normal subjects was assessed by multivariate linear regression. Measurements and Main Results: Normal PFTs were present in only 31 of 310 (10%) patients. Overall, adults with Hb-SS were characterized by decreased total lung capacities (70.2 ± 14.7% predicted) and DlCO (64.5 ± 19.9%). The most common PFT patterns were restrictive physiology (74%) and isolated low DlCO (13%). Decreased DLCO was associated with thrombocytosis (p = 0.05), with hepatic dysfunction (elevated alanine aminotransferase; p = 0.07), and a trend toward renal dysfunction (elevated blood urea nitrogen and creatinine; p = 0.05 and 0.07, respectively). Conclusions: Pulmonary function is abnormal in 90% of adult patients with Hb-SS. Common abnormalities include restrictive physiology and decreased DLCO. Decreased DLCO may indicate more severe sickle vasculopathy characterized by impaired hepatic and renal function. PMID:16556694

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

Are Adults Diagnosed with Diabetes achieving the American Diabetes Association Clinical Practice Recommendations?

Science.gov (United States)

Pérez, Cynthia M.; Febo-Vázquez, Isaedmarie; Guzmán, Manuel; Ortiz, Ana Patricia; Suárez, Erick

2012-01-01

Objective This study assessed the proportion of adults with previously diagnosed diabetes mellitus (DM) who met selected preventive practices and treatment goals according to the American Diabetes Association (ADA) standards of medical care. Methods A secondary analysis of data collected for a previous epidemiologic study that used a probability cluster design to select 859 persons aged 21–79 years in the San Juan metropolitan area was undertaken. This study focused on 136 (15.8%) adults who self-reported DM. The Standards of Medical Care in Diabetes published by the ADA in 2011 were used to determine the proportion of adults achieving selected clinical practice recommendations. Results Less than half of adults achieved recommended treatment goals for LDL-cholesterol (47.8%), HDL-cholesterol (44.1%), blood pressure (41.2%) and HbA1c (28.7%). The percentage of adults achieving recommended levels of HbA1c, blood pressure and LDL-cholesterol simultaneously was 6.6%; the percentage achieving HbA1c, blood pressure, LDL-cholesterol, HDL-cholesterol, triglycerides and albumin-to-creatinine ratio target levels was only 2.2%. More than half (60.2%) reported daily self-monitoring of foot ulcers and HbA1c testing at least twice over the past year (52.3%). However, less than half reported annual dilated eye examination (49.2%), annual comprehensive foot examination (43.8%), daily self-monitoring blood glucose (37.5%), moderate or vigorous physical activity (33.8%), and self-management DM education (28.9%). Conclusion This study showed that a substantial proportion of adults with DM did not achieve ADA recommendations on selected preventive practices and treatment goals. Strategies to improve DM medical care and surveillance of preventive-care practices and treatment goals among affected individuals are essential for planning further initiatives that contribute to reduce the burden of DM complications. PMID:22432404

Optical Spectra of Hemoglobin Taken from Alcohol Dependent Humans

OpenAIRE

Dudok K.; Dudok T.; Vlokh I.; Vlokh R.

2005-01-01

Optical spectra of CNMetHb and CNMetHb-Coomassi G-250, taken from the blood of humans with alcohol dependence, are studied in the spectral range of 450–750nm. The shifts in the spectral absorption maxima of CNMetHb-Coomassi G-250 complexes are observed for the diseased persons with alcohol dependence. The obtained results show that the hemoglobin structure of alcohol dependent humans is changed.

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

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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.

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

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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.

HbA2 measurements in β-thalassemia and in other conditions

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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.

Hemoglobin A1c Is Positively Correlated with Framingham Risk Score in Older, Apparently Healthy Nondiabetic Korean Adults

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Ji Hye Shin

2013-06-01

Full Text Available BackgroundSeveral studies have suggested that elevated levels of hemoglobin A1c (HbA1c are associated with cardiovascular disease (CVD in nondiabetic individuals. However, it is unclear whether HbA1c levels can serve as a simple screening marker for increased CVD risk in nondiabetic individuals. Our objective was to evaluate the relationship between HbA1c levels and CVD risk using the Framingham risk score (FRS in older, apparently healthy nondiabetic Korean adults.MethodsWe retrospectively studied 2,879 Korean adults between the ages of 40 and 79 who underwent voluntary health check-ups at the Health Promotion Center of our hospital from July 2009 to June 2011. Subjects were subdivided based on their HbA1c levels into four groups: tertiles within the HbA1c normal tolerance range and a group for subjects with an increased risk for diabetes (IRD.ResultsThe mean FRS for the upper tertile (9.6±3.8 group was significantly higher than that of the middle tertile (8.4±4.0 and lower tertile (7.6±3.8 groups. In addition, FRS was highest in the IRD group (10.5±3.7. Multiple linear regression analysis demonstrated that HbA1c levels exhibited a significant positive correlation with FRS when adjusted for confounding variables in all subjects (β±standard error [SE], 0.018±0.002; R2, 0.131, women (β±SE, 0.023±0.003; R2, 0.170, and men (β±SE, 0.016±0.004; R2, 0.109.ConclusionHbA1c levels were positively correlated with FRS in older, apparently healthy nondiabetic Korean adults. We propose that HbA1c levels may reflect CVD risk in nondiabetic individuals.

Expression and Purification of Recombinant Human Basic Fibroblast Growth Factor Fusion Proteins and Their Uses in Human Stem Cell Culture.

Science.gov (United States)

Imsoonthornruksa, Sumeth; Pruksananonda, Kamthorn; Parnpai, Rangsun; Rungsiwiwut, Ruttachuk; Ketudat-Cairns, Mariena

2015-01-01

To reduce the cost of cytokines and growth factors in stem cell research, a simple method for the production of soluble and biological active human basic fibroblast growth factor (hbFGF) fusion protein in Escherichia coli was established. Under optimal conditions, approximately 60-80 mg of >95% pure hbFGF fusion proteins (Trx-6xHis-hbFGF and 6xHis-hbFGF) were obtained from 1 liter of culture broth. The purified hbFGF proteins, both with and without the fusion tags, were biologically active, which was confirmed by their ability to stimulate proliferation of NIH3T3 cells. The fusion proteins also have the ability to support several culture passages of undifferentiated human embryonic stem cells and induce pluripotent stem cells. This paper describes a low-cost and uncomplicated method for the production and purification of biologically active hbFGF fusion proteins. © 2015 S. Karger AG, Basel.

Rapid determination of human globin chains using reversed-phase high-performance liquid chromatography.

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Wan, Jun-Hui; Tian, Pei-Ling; Luo, Wei-Hao; Wu, Bing-Yi; Xiong, Fu; Zhou, Wan-Jun; Wei, Xiang-Cai; Xu, Xiang-Min

2012-07-15

Reversed-phase high-performance liquid chromatography (RP-HPLC) of human globin chains is an important tool for detecting thalassemias and hemoglobin variants. The challenges of this method that limit its clinical application are a long analytical time and complex sample preparation. The aim of this study was to establish a simple, rapid and high-resolution RP-HPLC method for the separation of globin chains in human blood. Red blood cells from newborns and adults were diluted in deionized water and injected directly onto a micro-jupiter C18 reversed-phase column (250 mm × 4.6 mm) with UV detection at 280 nm. Under the conditions of varying pH or the HPLC gradient, the globin chains (pre-β, β, δ, α, (G)γ and (A)γ) were denatured and separated from the heme groups in 12 min with a retention time coefficient of variation (CV) ranging from 0.11 to 1.29% and a peak area CV between 0.32% and 4.86%. Significant differences (P<0.05) among three groups (normal, Hb H and β thalassemia) were found in the area ratio of α/pre-β+β applying the rapid elution procedure, while P≥0.05 was obtained between the normal and α thalassemia silent/trait group. Based on the ANOVA results, receiver operating characteristic (ROC) curve analysis of the δ/β and α/pre-β+β area ratios showed a sensitivity of 100.0%, and a specificity of 100.0% for indicating β thalassemia carriers, and a sensitivity of 96.6% and a specificity of 89.6% for the prediction of hemoglobin H (Hb H) disease. The proposed cut-off was 0.026 of δ/β for β thalassemia carriers and 0.626 of α/pre-β+β for Hb H disease. In addition, abnormal hemoglobin hemoglobin E (Hb E) and Hb Westmead (Hb WS) were successfully identified using this RP-HPLC method. Our experience in developing this RP-HPLC method for the rapid separation of human globin chains could be of use for similar work. Copyright © 2012 Elsevier B.V. All rights reserved.

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

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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.

In vitro proliferation of adult human beta-cells.

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Sabine Rutti

Full Text Available A decrease in functional beta-cell mass is a key feature of type 2 diabetes. Glucagon-like peptide 1 (GLP-1 analogues induce proliferation of rodent beta-cells. However, the proliferative capacity of human beta-cells and its modulation by GLP-1 analogues remain to be fully investigated. We therefore sought to quantify adult human beta-cell proliferation in vitro and whether this is affected by the GLP-1 analogue liraglutide.Human islets from 7 adult cadaveric organ donors were dispersed into single cells. Beta-cells were purified by FACS. Non-sorted cells and the beta-cell enriched ("beta-cells" population were plated on extracellular matrix from rat (804G and human bladder carcinoma cells (HTB9 or bovine corneal endothelial ECM (BCEC. Cells were maintained in culture+/-liraglutide for 4 days in the presence of BrdU.Rare human beta-cell proliferation could be observed either in the purified beta-cell population (0.051±0.020%; 22 beta-cells proliferating out of 84'283 beta-cells counted or in the non-sorted cell population (0.055±0.011%; 104 proliferating beta-cells out of 232'826 beta-cells counted, independently of the matrix or the culture conditions. Liraglutide increased human beta-cell proliferation on BCEC in the non-sorted cell population (0.082±0.034% proliferating beta-cells vs. 0.017±0.008% in control, p<0.05.These results indicate that adult human beta-cell proliferation can occur in vitro but remains an extremely rare event with these donors and particular culture conditions. Liraglutide increases beta-cell proliferation only in the non-sorted cell population and only on BCEC. However, it cannot be excluded that human beta-cells may proliferate to a greater extent in situ in response to natural stimuli.

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

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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.

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.

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�

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.

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.

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.

Neural correlates of obstacle negotiation in older adults: An fNIRS study.

Science.gov (United States)

Chen, Michelle; Pillemer, Sarah; England, Sarah; Izzetoglu, Meltem; Mahoney, Jeannette R; Holtzer, Roee

2017-10-01

Older adults are less efficient at avoiding obstacles compared to young adults, especially under attention-demanding conditions. Using functional near-infrared-spectroscopy (fNIRS), recent studies implicated the prefrontal cortex (PFC) in cognitive control of locomotion, notably under dual-task walking conditions. The neural substrates underlying Obstacle Negotiation (ON), however, have not been established. The current study determined the role of the PFC in ON during walking in seniors. Non-demented older adults (n=90; mean age=78.1±5.5years; %female=51) underwent fNIRS acquisition to assess changes in hemodynamic activity in the PFC during normal-walk [NW] and walk-while-talk [WWT] conditions with and without obstacles. Obstacles were presented as red elliptical shapes using advanced laser technology, which resemble potholes. Linear mixed effects models were used to determine differences in oxygenated hemoglobin (HbO 2 ) levels among the four task conditions. The presence of slow gait, a risk factor for dementia and falls, served as a predictor hypothesized to moderate the effect of obstacles on PFC HbO 2 levels. PFC HbO 2 levels were significantly higher in WWT compared to NW (p<0.001) irrespective of ON. Slow gait moderated the effect of obstacles on HbO 2 levels across task conditions. Specifically, compared to participants with normal gait, PFC HbO 2 levels were significantly increased in ON-NW relative to NW (p=0.017) and ON-WWT relative to WWT (p<0.001) among individuals with slow gait. Consistent with Compensatory Reallocation, ON required greater PFC involvement among individuals with mobility limitations. Copyright © 2017 Elsevier B.V. All rights reserved.

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.

Hemoglobin A1c and Mortality in Older Adults With and Without Diabetes: Results From the National Health and Nutrition Examination Surveys (1988-2011).

Science.gov (United States)

Palta, Priya; Huang, Elbert S; Kalyani, Rita R; Golden, Sherita H; Yeh, Hsin-Chieh

2017-04-01

Hemoglobin A 1c (HbA 1c ) level has been associated with increased mortality in middle-aged populations. The optimal intensity of glucose control in older adults with diabetes remains uncertain. We sought to estimate the risk of mortality by HbA 1c levels among older adults with and without diabetes. We analyzed data from adults aged ≥65 years ( n = 7,333) from the Third National Health and Nutrition Examination Survey (NHANES III) (1998-1994) and Continuous NHANES (1999-2004) and their linked mortality data (through December 2011). Cox proportional hazards models were used to examine the relationship of HbA 1c with the risk of all-cause and cause-specific (cardiovascular disease [CVD], cancer, and non-CVD/noncancer) mortality, separately for adults with diabetes and without diabetes. Over a median follow-up of 8.9 years, 4,729 participants died (1,262 from CVD, 850 from cancer, and 2,617 from non-CVD/noncancer causes). Compared with those with diagnosed diabetes and an HbA 1c 8.0%. HRs were 1.6 (95% CI 1.02, 2.6) and 1.8 (95% CI 1.3, 2.6) for HbA 1c 8.0-8.9% and ≥9.0%, respectively ( P for trend 6.5% had a 1.3 (95% CI 1.03, 1.8) times greater risk of all-cause mortality compared with participants without diabetes and HbA 1c 5.0-5.6%. An HbA 1c >8.0% was associated with increased risk of all-cause and cause-specific mortality in older adults with diabetes. Our results support the idea that better glycemic control is important for reducing mortality; however, in light of the conflicting evidence base, there is also a need for individualized glycemic targets for older adults with diabetes depending on their demographics, duration of diabetes, and existing comorbidities. © 2017 by the American Diabetes Association.

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.

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\

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.

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.

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...

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.

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 ...

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.

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 ...

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.

Improvements in the HbVar database of human hemoglobin variants and thalassemia mutations for population and sequence variation studies.

NARCIS (Netherlands)

G.P. Patrinos (George); B. Giardine (Belinda); C. Riemer (Cathy); W. Miller (Webb); D.H. Chui (David); N.P. Anagnou (Nicholas); H. Wajcman (Henri); R.C. Hardison (Ross)

2004-01-01

textabstractHbVar (http://globin.cse.psu.edu/globin/hbvar/) is a relational database developed by a multi-center academic effort to provide up-to-date and high quality information on the genomic sequence changes leading to hemoglobin variants and all types of thalassemia and

Editorial: Technology for higher education, adult learning and human performance

OpenAIRE

Minhong Wang; Chi-Cheng Chang; Feng Wu

2013-01-01

This special issue is dedicated to technology-enabled approaches for improving higher education, adult learning, and human performance. Improvement of learning and human development for sustainable development has been recognized as a key strategy for individuals, institutions, and organizations to strengthen their competitive advantages. It becomes crucial to help adult learners and knowledge workers to improve their self-directed and life-long learning capabilities. Meanwhile, advances in t...

Progress on the artificial rearing of the army worm, Spodoptera (Laphygma) exigua Hb. and radiation sterilization in the male of this species

International Nuclear Information System (INIS)

Loaharanu, S.; Chiravathanapong, S.

1971-01-01

The army worm, Spodoptera exigua Hb. was reared for 6 more generations in an artificial medium containing Mung bean as a major component. By improving the rearing temperature and humidity conditions, better rearing results were obtained. The average percentage of development from eggs to pupae, from eggs to adults, and from pupae to adults was 41.7+-4.93, 38.44+-6.32 and 88.1+-1.48 respectively. The pupal weight was also calculated. In sterilization studies, the 3-day-old male pupae were subjected to gamma rays at 0, 5 and 10 krads. Upon emerging into adults, they were mated with non-irradiated female moths. Male moths emerged from pupae subjected to 10 krads of gamma rays could significantly induce infertility in eggs deposited

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.

Age-Related Gene Expression Differences in Monocytes from Human Neonates, Young Adults, and Older Adults.

Science.gov (United States)

Lissner, Michelle M; Thomas, Brandon J; Wee, Kathleen; Tong, Ann-Jay; Kollmann, Tobias R; Smale, Stephen T

2015-01-01

A variety of age-related differences in the innate and adaptive immune systems have been proposed to contribute to the increased susceptibility to infection of human neonates and older adults. The emergence of RNA sequencing (RNA-seq) provides an opportunity to obtain an unbiased, comprehensive, and quantitative view of gene expression differences in defined cell types from different age groups. An examination of ex vivo human monocyte responses to lipopolysaccharide stimulation or Listeria monocytogenes infection by RNA-seq revealed extensive similarities between neonates, young adults, and older adults, with an unexpectedly small number of genes exhibiting statistically significant age-dependent differences. By examining the differentially induced genes in the context of transcription factor binding motifs and RNA-seq data sets from mutant mouse strains, a previously described deficiency in interferon response factor-3 activity could be implicated in most of the differences between newborns and young adults. Contrary to these observations, older adults exhibited elevated expression of inflammatory genes at baseline, yet the responses following stimulation correlated more closely with those observed in younger adults. Notably, major differences in the expression of constitutively expressed genes were not observed, suggesting that the age-related differences are driven by environmental influences rather than cell-autonomous differences in monocyte development.

Race-ethnic differences in the association of genetic loci with HbA1c levels and mortality in U.S. adults: the third National Health and Nutrition Examination Survey (NHANES III)

Science.gov (United States)

2012-01-01

Background Hemoglobin A1c (HbA1c) levels diagnose diabetes, predict mortality and are associated with ten single nucleotide polymorphisms (SNPs) in white individuals. Genetic associations in other race groups are not known. We tested the hypotheses that there is race-ethnic variation in 1) HbA1c-associated risk allele frequencies (RAFs) for SNPs near SPTA1, HFE, ANK1, HK1, ATP11A, FN3K, TMPRSS6, G6PC2, GCK, MTNR1B; 2) association of SNPs with HbA1c and 3) association of SNPs with mortality. Methods We studied 3,041 non-diabetic individuals in the NHANES (National Health and Nutrition Examination Survey) III. We stratified the analysis by race/ethnicity (NHW: non-Hispanic white; NHB: non-Hispanic black; MA: Mexican American) to calculate RAF, calculated a genotype score by adding risk SNPs, and tested associations with SNPs and the genotype score using an additive genetic model, with type 1 error = 0.05. Results RAFs varied widely and at six loci race-ethnic differences in RAF were significant (p HbA1c in NHW (β = 0.012 HbA1c increase per risk allele, p = 0.04) and MA (β = 0.021, p = 0.005) but not NHB (β = 0.007, p = 0.39). The genotype score was not associated with mortality in any group (NHW: OR (per risk allele increase in mortality) = 1.07, p = 0.09; NHB: OR = 1.04, p = 0.39; MA: OR = 1.03, p = 0.71). Conclusion At many HbA1c loci in NHANES III there is substantial RAF race-ethnic heterogeneity. The combined impact of common HbA1c-associated variants on HbA1c levels varied by race-ethnicity, but did not influence mortality. PMID:22540250

The weight of nations: an estimation of adult human biomass

Directory of Open Access Journals (Sweden)

Walpole Sarah

2012-06-01

Full Text Available Abstract Background The energy requirement of species at each trophic level in an ecological pyramid is a function of the number of organisms and their average mass. Regarding human populations, although considerable attention is given to estimating the number of people, much less is given to estimating average mass, despite evidence that average body mass is increasing. We estimate global human biomass, its distribution by region and the proportion of biomass due to overweight and obesity. Methods For each country we used data on body mass index (BMI and height distribution to estimate average adult body mass. We calculated total biomass as the product of population size and average body mass. We estimated the percentage of the population that is overweight (BMI > 25 and obese (BMI > 30 and the biomass due to overweight and obesity. Results In 2005, global adult human biomass was approximately 287 million tonnes, of which 15 million tonnes were due to overweight (BMI > 25, a mass equivalent to that of 242 million people of average body mass (5% of global human biomass. Biomass due to obesity was 3.5 million tonnes, the mass equivalent of 56 million people of average body mass (1.2% of human biomass. North America has 6% of the world population but 34% of biomass due to obesity. Asia has 61% of the world population but 13% of biomass due to obesity. One tonne of human biomass corresponds to approximately 12 adults in North America and 17 adults in Asia. If all countries had the BMI distribution of the USA, the increase in human biomass of 58 million tonnes would be equivalent in mass to an extra 935 million people of average body mass, and have energy requirements equivalent to that of 473 million adults. Conclusions Increasing population fatness could have the same implications for world food energy demands as an extra half a billion people living on the earth.

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.

[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.

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.

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

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.

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

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.

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

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.

Low and fixed dose of hydroxyurea is effective and safe in patients with HbSβ(+) thalassemia with IVS1-5(G→C) mutation.

Science.gov (United States)

Dehury, Snehadhini; Purohit, Prasanta; Patel, Siris; Meher, Satyabrata; Kullu, Bipin Kishore; Sahoo, Lulup Kumar; Patel, Nayan Kumar; Mohapatra, Alok Kumar; Das, Kishalaya; Patel, Dilip Kumar

2015-06-01

Despite compelling evidence that hydroxyurea is safe and effective in sickle cell disease, it is prescribed sparingly due to several barriers like knowledge gaps in certain genotypes, apprehension about its safety and toxicity, and limited resources. We undertook this study to find out the efficacy and safety of HU in patients with HbSβ(+) -thalassemia with IVS1-5(G→C) mutation. We registered 318 patients with HbSβ(+) -thalassemia with IVS1-5(G→C) mutation. Of these, 203 were enrolled for hydroxyurea treatment at a low and fixed dose of 10 mg/kg/day. One hundred four patients (Group-I: 37 children and Group-II: 67 adults) with ≥2 years of hydroxyurea treatment were studied. The rate of vaso-occlusive crises, requirement of blood transfusion and rate of hospitalization reduced from 3 to 0.5, 1 to 0 and 1 to 0 in Group-I and 3 to 0, 1 to 0 and 0.5 to 0 in Group-II respectively after HU therapy (P hydroxyurea is suitable for treatment of patients with HbSβ(+) -thalassemia in resource poor setting. © 2014 Wiley Periodicals, Inc.

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

The relationship between generic and diabetes specific psychological factors and glycaemic control in adults with type 1 diabetes

DEFF Research Database (Denmark)

Shaban, C.; Fosbury, J. A.; Cavan, D. A.

2009-01-01

259 adults with type 1 diabetes completed measure of anxiety, depression and diabetes specific distress, HbA1c from medical records. Anxiety not depression predicted HbA1c, this association was mediated by illness specific cognitions. Targeting illness specific cognitions may be more productive...

Fetal hemoglobin is much less prone to DNA cleavage compared to the adult protein

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Sandeep Chakane

2017-08-01

Full Text Available Hemoglobin (Hb is well protected inside the red blood cells (RBCs. Upon hemolysis and when free in circulation, Hb can be involved in a range of radical generating reactions and may thereby attack several different biomolecules. In this study, we have examined the potential damaging effects of cell-free Hb on plasmid DNA (pDNA. Hb induced cleavage of supercoiled pDNA (sc pDNA which was proportional to the concentration of Hb applied. Almost 70% of sc pDNA was converted to open circular or linear DNA using 10 µM of Hb in 12 h. Hb can be present in several different forms. The oxy (HbO2 and met forms are most reactive, while the carboxy-protein shows only low hydrolytic activity. Hemoglobin A (HbA could easily induce complete pDNA cleavage while fetal hemoglobin (HbF was three-fold less reactive. By inserting, a redox active cysteine residue on the surface of the alpha chain of HbF by site-directed mutagenesis, the DNA cleavage reaction was enhanced by 82%. Reactive oxygen species were not directly involved in the reaction since addition of superoxide dismutase and catalase did not prevent pDNA cleavage. The reactivity of Hb with pDNA can rather be associated with the formation of protein based radicals. Keywords: Adult hemoglobin, Fetal hemoglobin, Supercoiled plasmid DNA, DNA cleavage, Cysteine, Protein radicals

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

The cell-penetrating peptide domain from human heparin-binding epidermal growth factor-like growth factor (HB-EGF) has anti-inflammatory activity in vitro and in vivo

International Nuclear Information System (INIS)

Lee, Jue-Yeon; Seo, Yoo-Na; Park, Hyun-Jung; Park, Yoon-Jeong; Chung, Chong-Pyoung

2012-01-01

Highlights: ► HBP sequence identified from HB-EGF has cell penetration activity. ► HBP inhibits the NF-κB dependent inflammatory responses. ► HBP directly blocks phosphorylation and degradation of IκBα. ► HBP inhibits nuclear translocation of NF-κB p65 subunit. -- Abstract: A heparin-binding peptide (HBP) sequence from human heparin-binding epidermal growth factor-like growth factor (HB-EGF) was identified and was shown to exhibit cell penetration activity. This cell penetration induced an anti-inflammatory reaction in lipopolysaccharide (LPS)-treated RAW 264.7 macrophages. HBP penetrated the cell membrane during the 10 min treatment and reduced the LPS-induced production of nitric oxide (NO), inducible nitric oxide synthase (iNOS), and cytokines (TNF-α and IL-6) in a concentration-dependent manner. Additionally, HBP inhibited the LPS-induced upregulation of cytokines, including TNF-α and IL-6, and decreased the interstitial infiltration of polymorphonuclear leukocytes in a lung inflammation model. HBP inhibited NF-κB-dependent inflammatory responses by directly blocking the phosphorylation and degradation of IκBα and by subsequently inhibiting the nuclear translocation of the p65 subunit of NF-κB. Taken together, this novel HBP may be potentially useful candidate for anti-inflammatory treatments and can be combined with other drugs of interest to transport attached molecules into cells.

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.

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

Control of glycemia and other cardiovascular disease risk factors in older adults with type 2 diabetes mellitus: data from the Adult Diabetes Control and Management.

Science.gov (United States)

Sazlina, Shariff-Ghazali; Mastura, Ismail; Ahmad, Zaiton; Cheong, Ai-Theng; Adam, Bujang-Mohamad; Jamaiyah, Haniff; Lee, Ping-Yein; Syed-Alwi, Syed-Abdul-Rahman; Chew, Boon-How; Sriwahyu, Taher

2014-01-01

The aims of the present study were to assess the control of glycemia and other cardiovascular disease risk factors, and the association between age and these controls among older adults with type 2 diabetes in Malaysia. A cross-sectional study was carried out using cases notified to the Adult Diabetes Control and Management database between 1 January and 31 December 2009. A total of 10 363 people aged over 60 years with type 2 diabetes mellitus were included in the analyses. A standard online case report form was used to record demographic data, clinical factors (diabetes duration, comorbid condition and treatment modalities), cardiovascular disease risk factors, diabetes complications and laboratory assessments. The cardiovascular disease risk factors controls assessed included glycosylated hemoglobin (HbA(1c)) control of cardiovascular disease risk factors was suboptimal in older adults with type 2 diabetes. The oldest elderly were more likely to achieve target HbA(1c) (<7.0%) and triglycerides (<1.7 mmol/L) than older adults aged 60-69 years. © 2013 Japan Geriatrics Society.

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.

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

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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.

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%…

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...

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

Determination of extinction coefficients of human hemoglobin in various redox states.

Science.gov (United States)

Meng, Fantao; Alayash, Abdu I

2017-03-15

The role of hemoglobin (Hb) redox forms in tissue and organ toxicities remain ambiguous despite the well-documented contribution of Hb redox reactivity to cellular and subcellular oxidative changes. Moreover, several recent studies, in which Hb toxicity were investigated, have shown conflicting outcomes. Uncertainties over the potential role of these species may in part be due to the protein preparation method of choice, the use of published extinction coefficients and the lack of suitable controls for Hb oxidation and heme loss. Highly purified and well characterized redox forms of human Hb were used in this study and the extinction coefficients of each Hb species (ferrous/oxy, ferric/met and ferryl) were determined. A new set of equations were established to improve accuracy in determining the transient ferryl Hb species. Additionally, heme concentrations in solutions and in human plasma were determined using a novel reversed phase HPLC method in conjugation with our photometric measurements. The use of more accurate redox-specific extinction coefficients and method calculations will be an invaluable tool for both in vitro and in vivo experiments aimed at determining the role of Hb-mediated vascular pathology in hemolytic anemias and when Hb is used as oxygen therapeutics. Published by Elsevier Inc.

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.

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

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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.

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

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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.

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

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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.

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

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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

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

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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.

Can sleep deprivation studies explain why human adults sleep?

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Brown, Lee K

2012-11-01

This review will concentrate on the consequences of sleep deprivation in adult humans. These findings form a paradigm that serves to demonstrate many of the critical functions of the sleep states. The drive to obtain food, water, and sleep constitutes important vegetative appetites throughout the animal kingdom. Unlike nutrition and hydration, the reasons for sleep have largely remained speculative. When adult humans are nonspecifically sleep-deprived, systemic effects may include defects in cognition, vigilance, emotional stability, risk-taking, and, possibly, moral reasoning. Appetite (for foodstuffs) increases and glucose intolerance may ensue. Procedural, declarative, and emotional memory are affected. Widespread alterations of immune function and inflammatory regulators can be observed, and functional MRI reveals profound changes in regional cerebral activity related to attention and memory. Selective deprivation of rapid eye movement (REM) sleep, on the contrary, appears to be more activating and to have lesser effects on immunity and inflammation. The findings support a critical need for sleep due to the widespread effects on the adult human that result from nonselective sleep deprivation. The effects of selective REM deprivation appear to be different and possibly less profound, and the functions of this sleep state remain enigmatic.

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

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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.

A nomogram to estimate the HbA1c response to different DPP-4 inhibitors in type 2 diabetes: a systematic review and meta-analysis of 98 trials with 24 163 patients

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Esposito, Katherine; Chiodini, Paolo; Maiorino, Maria Ida; Capuano, Annalisa; Cozzolino, Domenico; Petrizzo, Michela; Bellastella, Giuseppe; Giugliano, Dario

2015-01-01

Objectives To develop a nomogram for estimating the glycated haemoglobin (HbA1c) response to different dipeptidyl peptidase-4 (DPP-4) inhibitors in type 2 diabetes. Design A systematic review and meta-analysis of randomised controlled trials (RCTs) of DPP-4 inhibitors (vildagliptin, sitagliptin, saxagliptin, linagliptin and alogliptin) on HbA1c were conducted. Electronic searches were carried out up to December 2013. Trials were included if they were carried out on participants with type 2 diabetes, lasted at least 12 weeks, included at least 30 participants and had a final assessment of HbA1c. A random effect model was used to pool data. A nomogram was used to represent results of the metaregression model. Participants Adults with type 2 diabetes. Interventions Any DPP-4 inhibitor (vildagliptin, sitagliptin, saxagliptin, linagliptin or alogliptin). Outcome measures The HbA1c response to each DPP-4 inhibitor within 1 year of therapy. Results We screened 928 citations and reviewed 98 articles reporting 98 RCTs with 100 arms in 24 163 participants. There were 26 arms with vildagliptin, 37 with sitagliptin, 13 with saxagliptin, 13 with linagliptin and 11 with alogliptin. For all 100 arms, the mean baseline HbA1c value was 8.05% (64 mmol/mol); the decrease of HbA1c from baseline was −0.77% (95% CI −0.82 to −0.72%), with high heterogeneity (I2=96%). Multivariable metaregression model that included baseline HbA1c, type of DPP-4 inhibitor and fasting glucose explained 58% of variance between studies, with no significant interaction between them. Other factors, including age, previous diabetes drugs and duration of treatment added low predictive power (HbA1c reduction from baseline using the type of DPP-4 inhibitor, baseline values of HbA1c and fasting glucose. Conclusions Baseline HbA1c level and fasting glucose explain most of the variance in HbA1c change in response to DPP-4 inhibitors: each increase of 1.0% units HbA1c provides a 0.4–0.5% units greater

Race-ethnic differences in the association of genetic loci with HbA1c levels and mortality in U.S. adults: the third National Health and Nutrition Examination Survey (NHANES III

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Grimsby Jonna L

2012-04-01

Full Text Available Abstract Background Hemoglobin A1c (HbA1c levels diagnose diabetes, predict mortality and are associated with ten single nucleotide polymorphisms (SNPs in white individuals. Genetic associations in other race groups are not known. We tested the hypotheses that there is race-ethnic variation in 1 HbA1c-associated risk allele frequencies (RAFs for SNPs near SPTA1, HFE, ANK1, HK1, ATP11A, FN3K, TMPRSS6, G6PC2, GCK, MTNR1B; 2 association of SNPs with HbA1c and 3 association of SNPs with mortality. Methods We studied 3,041 non-diabetic individuals in the NHANES (National Health and Nutrition Examination Survey III. We stratified the analysis by race/ethnicity (NHW: non-Hispanic white; NHB: non-Hispanic black; MA: Mexican American to calculate RAF, calculated a genotype score by adding risk SNPs, and tested associations with SNPs and the genotype score using an additive genetic model, with type 1 error = 0.05. Results RAFs varied widely and at six loci race-ethnic differences in RAF were significant (p ATP11A, the SNP RAF was 54% in NHB, 18% in MA and 14% in NHW (p 1c in NHW (β = 0.012 HbA1c increase per risk allele, p = 0.04 and MA (β = 0.021, p = 0.005 but not NHB (β = 0.007, p = 0.39. The genotype score was not associated with mortality in any group (NHW: OR (per risk allele increase in mortality = 1.07, p = 0.09; NHB: OR = 1.04, p = 0.39; MA: OR = 1.03, p = 0.71. Conclusion At many HbA1c loci in NHANES III there is substantial RAF race-ethnic heterogeneity. The combined impact of common HbA1c-associated variants on HbA1c levels varied by race-ethnicity, but did not influence mortality.

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

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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.

Post-translational transformation of methionine to aspartate is catalyzed by heme iron and driven by peroxide: a novel subunit-specific mechanism in hemoglobin.

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Strader, Michael Brad; Hicks, Wayne A; Kassa, Tigist; Singleton, Eileen; Soman, Jayashree; Olson, John S; Weiss, Mitchell J; Mollan, Todd L; Wilson, Michael T; Alayash, Abdu I

2014-08-08

A pathogenic V67M mutation occurs at the E11 helical position within the heme pockets of variant human fetal and adult hemoglobins (Hb). Subsequent post-translational modification of Met to Asp was reported in γ subunits of human fetal Hb Toms River (γ67(E11)Val → Met) and β subunits of adult Hb (HbA) Bristol-Alesha (β67(E11)Val → Met) that were associated with hemolytic anemia. Using kinetic, proteomic, and crystal structural analysis, we were able to show that the Met → Asp transformation involves heme cycling through its oxoferryl state in the recombinant versions of both proteins. The conversion to Met and Asp enhanced the spontaneous autoxidation of the mutants relative to wild-type HbA and human fetal Hb, and the levels of Asp were elevated with increasing levels of hydrogen peroxide (H2O2). Using H2(18)O2, we verified incorporation of (18)O into the Asp carboxyl side chain confirming the role of H2O2 in the oxidation of the Met side chain. Under similar experimental conditions, there was no conversion to Asp at the αMet(E11) position in the corresponding HbA Evans (α62(E11)Val → Met). The crystal structures of the three recombinant Met(E11) mutants revealed similar thioether side chain orientations. However, as in the solution experiments, autoxidation of the Hb mutant crystals leads to electron density maps indicative of Asp(E11) formation in β subunits but not in α subunits. This novel post-translational modification highlights the nonequivalence of human Hb α, β, and γ subunits with respect to redox reactivity and may have direct implications to α/β hemoglobinopathies and design of oxidatively stable Hb-based oxygen therapeutics. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Contact and perspective taking improve humanness standards and perceptions of humanness of older adults and people with dementia: a cross-sectional survey study.

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Miron, Anca M; McFadden, Susan H; Hermus, Nathan J; Buelow, Jennifer; Nazario, Amanda S; Seelman, Katarena

2017-10-01

No empirical work has systematically explored perceptions of humanness of people with dementia and of older adults and the variables that could improve these perceptions. We thus investigated the role of contact and perspective taking in improving perceptions of humanness of these social groups. To do so, we developed a new concept, humanness standards, defined as the amount of evidence of ability impairment needed to conclude that elderly people and those with dementia have lost personhood. We used a cross-sectional survey design (n = 619) to assess participants' humanness standards and perceptions of uniquely human characteristics and human nature characteristics of two social groups (people with dementia and older adults). Half the participants (n = 311) completed a survey about people with dementia and half (n = 308) assessed older adults. People with dementia were perceived as possessing humanness characteristics to a lesser extent than were older adults. For both groups, contact predicted enhanced perceptions of humanness characteristics. Participants' degree of contact with individuals with dementia also predicted humanness standards, but only under low perspective-taking conditions. As predicted, for older adults, participants set the highest humanness impairment thresholds in the high contact/high perspective-taking condition. We conclude that while social programs that bring persons with dementia and other individuals in contact could change humanness standards and perceptions of humanness characteristics of people with dementia, in the case of elderly adults, the contact must be supplemented by variables that facilitate taking the perspective of the person.

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.

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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.

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.

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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.

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

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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.

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

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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.

Use of HbA1c for Diagnoses of Diabetes and Prediabetes: Comparison with Diagnoses Based on Fasting and 2-Hr Glucose Values and Effects of Gender, Race, and Age

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Moellering, Douglas R.

2014-01-01

Abstract Background: Glycated hemoglobin (HbA1c) has been advocated for the diagnosis of diabetes and prediabetes. Its performance has been commonly assessed in corroboration with elevated fasting plasma glucose (FPG), but not the combination of FPG and 2-hr glucose values. This study assesses receiver operating characteristics (ROC) curves of HbA1c pertaining to the diagnoses of prediabetes and diabetes by FPG and/or 2-hr glucose, and the effects of age, gender, and race. Methods: We assessed the utility of HbA1c for diagnosing diabetes and prediabetes among 5395 adults without known diabetes from the National Health and Nutrition Examination Survey (NHANES) 2005–2010. Results: Current cutoffs of HbA1c for diabetes (6.5%) or prediabetes (5.7%) exhibited low sensitivity (0.249 and 0.354, respectively) and high specificity in identifying patients diagnosed using both FPG and 2-hr glucose, resulting in large false-negative rates (75.1% and 64.9%). Misdiagnosis rates increased with age and in non-Hispanic whites and Mexican Americans. When HbA1c was combined with FPG for diagnoses, the false-negative rate remained high for diabetes (45.7%), but was reduced for prediabetes (9.2%). Conclusions: When assessed against diagnoses using both FPG and 2-hr glucose, HbA1c had low sensitivity and high specificity for identifying diabetes and prediabetes, which varied as a function of age and race. Regarding recently released American Diabetes Association (ADA) and joint European guidelines, it is important to consider that HbA1c values below 6.5% and 5.7% do not reliably exclude the presence of diabetes and prediabetes, respectively. Overall, the data argue for greater use of oral glucose tolerance tests (OGTTs) and both FPG and 2-hr glucose values for diagnosis of diabetes and prediabetes. PMID:24512556

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

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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.

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

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.

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

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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.

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

Glutathione Redox System in β-Thalassemia/Hb E Patients

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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.

Race-ethnic differences in the association of genetic loci with HbA1c levels and mortality in U.S. adults: the third National Health and Nutrition Examination Survey (NHANES III).

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Grimsby, Jonna L; Porneala, Bianca C; Vassy, Jason L; Yang, Quanhe; Florez, José C; Dupuis, Josée; Liu, Tiebin; Yesupriya, Ajay; Chang, Man-Huei; Ned, Renee M; Dowling, Nicole F; Khoury, Muin J; Meigs, James B

2012-04-27

Hemoglobin A1c (HbA1c) levels diagnose diabetes, predict mortality and are associated with ten single nucleotide polymorphisms (SNPs) in white individuals. Genetic associations in other race groups are not known. We tested the hypotheses that there is race-ethnic variation in 1) HbA1c-associated risk allele frequencies (RAFs) for SNPs near SPTA1, HFE, ANK1, HK1, ATP11A, FN3K, TMPRSS6, G6PC2, GCK, MTNR1B; 2) association of SNPs with HbA1c and 3) association of SNPs with mortality. We studied 3,041 non-diabetic individuals in the NHANES (National Health and Nutrition Examination Survey) III. We stratified the analysis by race/ethnicity (NHW: non-Hispanic white; NHB: non-Hispanic black; MA: Mexican American) to calculate RAF, calculated a genotype score by adding risk SNPs, and tested associations with SNPs and the genotype score using an additive genetic model, with type 1 error = 0.05. RAFs varied widely and at six loci race-ethnic differences in RAF were significant (p differed by race-ethnicity (NHW: 10.4, NHB: 11.0, MA: 10.7, p race-ethnic heterogeneity. The combined impact of common HbA1c-associated variants on HbA1c levels varied by race-ethnicity, but did not influence mortality.

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

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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

Oogenesis in cultures derived from adult human ovaries

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Caudle Michael R

2005-05-01

Full Text Available Abstract Ten years ago, we reported that in adult human females the ovarian surface epithelium (OSE is a source of germ cells. Recently, we also demonstrated that new primary follicles are formed by assembly of oocytes with nests of primitive granulosa cells in the ovarian cortex. The components of the new primary follicles, primitive granulosa and germ cells, differentiated sequentially from the OSE, which arises from cytokeratin positive mesenchymal progenitor cells residing in the ovarian tunica albuginea. In the present study, we investigated the possibility that the oocytes and granulosa cells may differentiate in cultures derived from adult human ovaries. Cells were scrapped from the surface of ovaries and cultured for 5 to 6 days, in the presence or absence of estrogenic stimuli [phenol red (PhR]. The OSE cells cultured in the medium without PhR differentiated into small (15 micron cells of granulosa phenotype, and epithelial, neural, and mesenchymal type cells. In contrast, OSE cells cultured in the presence of PhR differentiated directly into large (180 micron cells of the oocyte phenotype. Such cells exhibited germinal vesicle breakdown, expulsion of the polar body, and surface expression of zona pellucida proteins, i.e. characteristics of secondary oocytes. These in vitro studies confirm our in vivo observations that in adult human ovaries, the OSE is a bipotent source of oocytes and granulosa cells. Development of numerous mature oocytes from adult ovarian stem cells in vitro offers new strategies for the egg preservation, IVF utilization, and treatment of female infertility. In addition, other clinical applications aiming to utilize stem cells, and basic stem cell research as well, may employ totipotent embryonic stem cells developing from fertilized oocytes.

Distinct functional programming of human fetal and adult monocytes.

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Krow-Lucal, Elisabeth R; Kim, Charles C; Burt, Trevor D; McCune, Joseph M

2014-03-20

Preterm birth affects 1 out of 9 infants in the United States and is the leading cause of long-term neurologic handicap and infant mortality, accounting for 35% of all infant deaths in 2008. Although cytokines including interferon-γ (IFN-γ), interleukin-10 (IL-10), IL-6, and IL-1 are produced in response to in utero infection and are strongly associated with preterm labor, little is known about how human fetal immune cells respond to these cytokines. We demonstrate that fetal and adult CD14(+)CD16(-) classical monocytes are distinct in terms of basal transcriptional profiles and in phosphorylation of signal transducers and activators of transcription (STATs) in response to cytokines. Fetal monocytes phosphorylate canonical and noncanonical STATs and respond more strongly to IFN-γ, IL-6, and IL-4 than adult monocytes. We demonstrate a higher ratio of SOCS3 to IL-6 receptor in adult monocytes than in fetal monocytes, potentially explaining differences in STAT phosphorylation. Additionally, IFN-γ signaling results in upregulation of antigen presentation and costimulatory machinery in adult, but not fetal, monocytes. These findings represent the first evidence that primary human fetal and adult monocytes are functionally distinct, potentially explaining how these cells respond differentially to cytokines implicated in development, in utero infections, and the pathogenesis of preterm labor.

Understanding Older Adult's Perceptions of Factors that Support Trust in Human and Robot Care Providers.

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Stuck, Rachel E; Rogers, Wendy A

2017-06-01

As the population of older adults increase so will the need for care providers, both human and robot. Trust is a key aspect to establish and maintain a successful older adult-care provider relationship. However, due to trust volatility it is essential to understand it within specific contexts. This proposed mixed methods study will explore what dimensions of trust emerge as important within the human-human and human-robot dyads in older adults and care providers. First, this study will help identify key qualities that support trust in a care provider relationship. By understanding what older adults perceive as needing to trust humans and robots for various care tasks, we can begin to provide recommendations based on user expectations for design to support trust.

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

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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.

Cerebral time domain-NIRS: Reproducibility analysis, optical properties, hemoglobin species and tissue oxygen saturation in a cohort of adult subjects

OpenAIRE

Giacalone, Giacomo; Zanoletti, Marta; Contini, Davide; Rebecca, Re; Spinelli, Lorenzo; Roveri, Luisa; Torricelli, Alessandro

2017-01-01

The reproducibility of cerebral time-domain near-infrared spectroscopy (TD-NIRS) has not been investigated so far. Besides, reference intervals of cerebral optical properties, of absolute concentrations of deoxygenated-hemoglobin (HbR), oxygenated-hemoglobin (HbO), total hemoglobin (HbT) and tissue oxygen saturation (StO2) and their variability have not been reported. We have addressed these issues on a sample of 88 adult healthy subjects. TD-NIRS measurements at 690, 785, 830 nm were fitted ...

Models of human operators

International Nuclear Information System (INIS)

Knee, H.E.; Schryver, J.C.

1991-01-01

Models of human behavior and cognition (HB and C) are necessary for understanding the total response of complex systems. Many such models have come available over the past thirty years for various applications. Unfortunately, many potential model users remain skeptical about their practicality, acceptability, and usefulness. Such hesitancy stems in part to disbelief in the ability to model complex cognitive processes, and a belief that relevant human behavior can be adequately accounted for through the use of commonsense heuristics. This paper will highlight several models of HB and C and identify existing and potential applications in attempt to dispel such notions. (author)

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

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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

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

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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.

Does Acute Normobaric Hypoxia Induce Anapyrexia in Adult Humans?

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Seo, Yongsuk; Gerhart, Hayden D; Vaughan, Jeremiah; Kim, Jung-Hyun; Glickman, Ellen L

2017-06-01

Seo, Yongsuk, Hayden D. Gerhart, Jeremiah Vaughan, Jung-Hyun Kim, and Ellen L. Glickman. Does acute normobaric hypoxia induce anapyrexia in adult humans? High Alt Med Biol. 18:185-190, 2017.-Exposure to hypoxia is known to induce a reduction in core body temperature as a protective mechanism, which has been shown in both animals and humans. The purpose of this study was to test if acute exposure to normobaric hypoxia (NH) induces anapyrexia in adult humans in association with decreased peripheral oxygen saturation (SpO 2 ). Ten healthy male subjects were seated in atmospheres of normobaric normoxia 21% (NN21), NH 17% (NH17), and 13% (NH13) O 2 for 60 minutes in a counterbalanced manner. Rectal temperature (Tre) was continuously monitored together with the quantification of metabolic heat production (MHP) and body heat storage (S). Baseline physiological measurements showed no differences between the three conditions. SpO 2 was significantly decreased in NH17 and NH13 compared with NN21 (p ≤ 0.001). Tre decreased following 60 minutes of resting in all conditions, but, independent of the conditions, showed no association between Tre and levels of hypoxic SpO 2 . There was also no significant difference in either MHP or S between conditions. The present results showed no evidence of hypoxia-induced anapyrexia in adult humans during 1 hour of resting after exposure to NH either at 13% or 17% O 2 .

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.

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.

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

The moderating effect of social cognitive factors on self-management activities and HbA1c in Thai adults with type-2 diabetes

Directory of Open Access Journals (Sweden)

Somsak Thojampa

2017-01-01

Conclusion: The diabetes self-management activities were more strongly associated with HbA1c under conditions of high social support, self-efficacy and health beliefs with Buddhist values. Future interventions for T2DM self-management programs should incorporate mechanisms to measure and support these factors.

Inclusion bodies in loggerhead erythrocytes are associated with unstable hemoglobin and resemble human Heinz bodies.

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Basile, Filomena; Di Santi, Annalisa; Caldora, Mercedes; Ferretti, Luigi; Bentivegna, Flegra; Pica, Alessandra

2011-08-01

The aim of this study was to clarify the role of the erythrocyte inclusions found during the hematological screening of loggerhead population of the Mediterranean Sea. We studied the erythrocyte inclusions in blood specimens collected from six juvenile and nine adult specimens of the loggerhead turtle, Caretta caretta, from the Adriatic and Tyrrhenian Seas. Our study indicates that the percentage of mature erythrocytes containing inclusions ranged from 3 to 82%. Each erythrocyte contained only one round inclusion body. Inclusion bodies stained with May Grünwald-Giemsa show that their cytochemical and ultrastructure characteristics are identical to those of human Heinz bodies. Because Heinz bodies originate from the precipitation of unstable hemoglobin (Hb) and cause globular osmotic resistance to increase, we analyzed loggerhead Hb using electrophoresis and high-performance liquid chromatography to detect and quantitate Hb fractions. We also tested the resistance of Hb to alkaline pH, heat, isopropanol denaturation, and globular osmosis. Our hemogram results excluded the occurrence of any infection, which could be associated with an inclusion body, in all the specimens. Negative Feulgen staining indicated that the inclusion bodies are not derived from DNA fragmentation. We hypothesize that amino acid substitutions could explain why loggerhead Hb precipitates under normal physiologic conditions, forming Heinz bodies. The identification of inclusion bodies in loggerhead erythrocytes allow us to better understand the haematological characteristics and the physiology of these ancient reptiles, thus aiding efforts to conserve such an endangered species. Copyright © 2011 Wiley-Liss, Inc., A Wiley Company.

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.

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

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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.

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

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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.

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

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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.

On the Metabolism of Exogenous Ketones in Humans

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Brianna J. Stubbs

2017-10-01

Full Text Available Background and aims: Currently there is considerable interest in ketone metabolism owing to recently reported benefits of ketosis for human health. Traditionally, ketosis has been achieved by following a high-fat, low-carbohydrate “ketogenic” diet, but adherence to such diets can be difficult. An alternative way to increase blood D-β-hydroxybutyrate (D-βHB concentrations is ketone drinks, but the metabolic effects of exogenous ketones are relatively unknown. Here, healthy human volunteers took part in three randomized metabolic studies of drinks containing a ketone ester (KE; (R-3-hydroxybutyl (R-3-hydroxybutyrate, or ketone salts (KS; sodium plus potassium βHB.Methods and Results: In the first study, 15 participants consumed KE or KS drinks that delivered ~12 or ~24 g of βHB. Both drinks elevated blood D-βHB concentrations (D-βHB Cmax: KE 2.8 mM, KS 1.0 mM, P < 0.001, which returned to baseline within 3–4 h. KS drinks were found to contain 50% of the L-βHB isoform, which remained elevated in blood for over 8 h, but was not detectable after 24 h. Urinary excretion of both D-βHB and L-βHB was <1.5% of the total βHB ingested and was in proportion to the blood AUC. D-βHB, but not L-βHB, was slowly converted to breath acetone. The KE drink decreased blood pH by 0.10 and the KS drink increased urinary pH from 5.7 to 8.5. In the second study, the effect of a meal before a KE drink on blood D-βHB concentrations was determined in 16 participants. Food lowered blood D-βHB Cmax by 33% (Fed 2.2 mM, Fasted 3.3 mM, P < 0.001, but did not alter acetoacetate or breath acetone concentrations. All ketone drinks lowered blood glucose, free fatty acid and triglyceride concentrations, and had similar effects on blood electrolytes, which remained normal. In the final study, participants were given KE over 9 h as three drinks (n = 12 or a continuous nasogastric infusion (n = 4 to maintain blood D-βHB concentrations greater than 1 mM. Both drinks

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

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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.

Prevalence of psychological symptoms among adults with sickle cell disease in Korle-Bu Teaching Hospital, Ghana

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Michael Tetteh Anim

2016-11-01

Full Text Available Abstract Background Previous research revealed high prevalence of psychological symptoms among sickle cell disease (SCD patients in the West and Europe. In some Black SCD populations such as Nigeria and Jamaica, anxiety and depression had low prevalence rates compared to Europe. With difficulty locating research data on the prevalence of psychological symptoms in Ghana, this study aimed at exploring psychological symptoms among adults with SCD in a Teaching Hospital in Accra, Ghana. Methods Two hundred and one participants (males 102 and females 99 who were HbSS (n = 131 and HbSC (n = 70, aged 18 years and above were purposively recruited. Using the Brief Symptom Inventory (BSI in a cross-sectional survey, the research answered questions about the prevalence of psychological symptoms. It also examined gender and genotype differences in psychological symptoms scores. Results Results indicated that adults with SCD had non-distress psychological symptoms scores. Although paranoid ideation as a psychological symptom indicated “a little bit” score, its prevalence was only 1 %. The prevalence of psychological symptoms as indexed by the Positive Symptom Total (PST was 10 %. Anxiety, hostility, and depression were psychological symptoms with low scores. Furthermore, except psychoticism scores, males did not differ significantly from females in other psychological symptoms. On the contrary, HbSS participants differed significantly, reporting more psychological symptoms than their HbSC counterparts. Conclusions The study concluded that there was low prevalence of psychological symptoms among adults with SCD in this Ghanaian study. Although psychological symptoms distress scores were not observed among study participants at this time, females differed significantly by experiencing more psychoticism symptoms than males. HbSS participants also differed significantly by experiencing more depression, phobic anxiety, paranoid ideation

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

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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%.

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

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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.

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

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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.

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.)

Interaction of hemoglobin Grey Lynn (Vientiane) with a non-deletional α(+)-thalassemia in an adult Thai proband.

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Singha, Kritsada; Fucharoen, Goonnapa; Fucharoen, Supan

2014-01-01

Hemoglobin (Hb) Grey Lynn is a Hb variant caused by a substitution of Phe for Leu at position 91 of α1-globin chain, originally described in individual of unknown ethnic background. This article addresses the interaction of Hb Grey Lynn with a non-deletional α(+)-thalassemia found in Thailand, a hitherto un-described condition. The proband was adult Thai woman referred for investigation of mild anemia with Hb 90 g/L. Hb analyses using low pressure liquid chromatography raised a suspicion of abnormal Hb presence, which was failed to demonstrate by cellulose acetate electrophoresis and capillary electrophoresis. DNA sequencing identified a CTT (Leu) to TTT (Phe) mutation at codon 91 corresponding to the Hb Grey Lynn (Vientiane) [α91(FG3)Leu>Phe (α1) on α1-globin gene and a C deletion between codons 36 and 37 on α2-globin gene causing α(+)-thalassemia. As compared to those observed in a compound heterozygote for Hb Grey Lynn / α(0)-thalassemia reported previously, higher MCV (81.7 fL) and MCH (26.3 pg) values with a lower level of Hb Grey Lynn (19.7%) were observed in the proband. The normochromic normocytic anemia observed could be due to the interaction of Hb Grey Lynn with α(+)-thalassemia. The two mutations could be identified using PCR-RFLP and allele-specific PCR assays developed.

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

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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.

Development and application of the Chinese adult female computational phantom Rad-HUMAN

International Nuclear Information System (INIS)

Wu, Yican; Cheng, Mengyun; Wang, Wen; Fan, Yanchang; Zhao, Kai; He, Tao; Pei, Xi; Shang, Leiming; Chen, Chaobin; Long, Pengcheng; Cao, Ruifen; Wang, Guozhong; Zhou, Shaoheng; Yu, Shengpeng; Hu, Liqin; Zeng, Q.

2013-01-01

Rad-HUMAN is a whole-body numerical phantom of a Chinese adult woman which contains 46 organs and tissues and was created by MCAM6 software using the color photographs of the Chinese Visible Human dataset. This dataset was obtained from a 22-year old Chinese female cadaver judged to represent normal human anatomy as much as possible. The density and elemental composition recommended in the ICRP Publication 89 and in the ICRU report 44 were assigned to the organ and tissue in Rad-HUMAN for radiation protection purpose. The last step was to implement the anatomical data into a Monte Carlo code. Rad-HUMAN contains more than 28.8 billion tiny volume units, which produces an accurately whole-body numerical phantom of a Chinese adult female

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

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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.

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

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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.

Blood spot-based measures of glucose homeostasis and diabetes prevalence in a nationally representative population of young US adults.

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Nguyen, Quynh C; Whitsel, Eric A; Tabor, Joyce W; Cuthbertson, Carmen C; Wener, Mark H; Potter, Alan J; Halpern, Carolyn T; Killeya-Jones, Ley A; Hussey, Jon M; Suchindran, Chirayath; Harris, Kathleen Mullan

2014-12-01

We investigated understudied biomarker-based diabetes among young US adults, traditionally characterized by low cardiovascular disease risk. We examined 15,701 participants aged 24 to 32 years at Wave IV of the National Longitudinal Study of Adolescent Health (Add Health, 2008). The study used innovative and relatively noninvasive methods to collect capillary whole blood via finger prick at in-home examinations in all 50 states. Assays of dried blood spots produced reliable and accurate values of HbA1c. Reliability was lower for fasting glucose and lowest for random glucose. Mean (SD) HbA1c was 5.6% (0.8%). More than a quarter (27.4%) had HbA1c-defined prediabetes. HbA1c was highest in the black, non-Hispanic race/ethnic group, inversely associated with education, and more common among the overweight/obese and physically inactive. The prevalence of diabetes defined by previous diagnosis or use of antidiabetic medication was 2.9%. Further incorporating HbA1c and glucose values, the prevalence increased to 6.8%, and among these participants, 38.9% had a previous diagnosis of diabetes (i.e., aware). Among those aware, 37.6% were treated and 64.0% were controlled (i.e., HbA1c young adults faces a historically high risk of diabetes but there is ample opportunity for early detection and intervention. Copyright © 2014 Elsevier Inc. All rights reserved.

Hope matters to the glycemic control of adolescents and young adults with type 1 diabetes.

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Santos, Fábio R M; Sigulem, Daniel; Areco, Kelsy C N; Gabbay, Monica A L; Dib, Sergio A; Bernardo, Viviane

2015-05-01

This study investigated the association of hope and its factors with depression and glycemic control in adolescents and young adults with type 1 diabetes. A total of 113 patients were invited to participate. Significant negative correlations were found between hope and HbA1c and also between hope and depression. Hope showed a significant association with HbA1c and depression in the stepwise regression model. Among the hope factors, "inner positive expectancy" was significantly associated with HbA1c and depression. This study supports that hope matters to glycemic control and depression. Intervention strategies focusing on hope should be further explored. © The Author(s) 2015.

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

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

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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.

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

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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

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.

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

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.

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.

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.

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

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.

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).

Routine monitoring of diabetes mellitus in adults at primary health ...

African Journals Online (AJOL)

Glycaemic targets for control in type 1 diabetes mellitus* .... CGM can be useful in selected adults older than 25 years with type 1 diabetes to lower the HbA1c .... Lifestyle modifications should be addressed regularly, including weight loss if ...

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.

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

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.

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.

A role for the epidermal growth factor receptor signaling in development of intestinal serrated polyps in mice and humans.

Science.gov (United States)

Bongers, Gerold; Muniz, Luciana R; Pacer, Michelle E; Iuga, Alina C; Thirunarayanan, Nanthakumar; Slinger, Erik; Smit, Martine J; Reddy, E Premkumar; Mayer, Lloyd; Furtado, Glaucia C; Harpaz, Noam; Lira, Sergio A

2012-09-01

Epithelial cancers can be initiated by activating mutations in components of the mitogen-activated protein kinase signaling pathway such as v-raf murine sarcoma viral oncogene homolog B1 (BRAF), v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS), or epidermal growth factor receptor (EGFR). Human intestinal serrated polyps are a heterogeneous group of benign lesions, but some progress to colorectal cancer. Tumors that arise from these polyps frequently contain activating mutations in BRAF or KRAS, but little is known about the role of EGFR activation in their development. Polyp samples were obtained from adults during screening colonoscopies at Mount Sinai Hospital in New York. We measured levels of EGFR protein and phosphorylation in human serrated polyps by immunohistochemical and immunoblot analyses. We generated transgenic mice that express the ligand for EGFR, Heparin-binding EGF-like growth factor (HB-EGF), in the intestine. EGFR and the extracellular-regulated kinases (ERK)1/2 were phosphorylated in serrated areas of human hyperplastic polyps (HPPs), sessile serrated adenomas, and traditional serrated adenomas. EGFR and ERK1/2 were phosphorylated in the absence of KRAS or BRAF activating mutations in a subset of HPP. Transgenic expression of the EGFR ligand HB-EGF in the intestines of mice promoted development of small cecal serrated polyps. Mice that expressed a combination of HB-EGF and US28 (a constitutively active, G-protein-coupled receptor that increases processing of HB-EGF from the membrane) rapidly developed large cecal serrated polyps. These polyps were similar to HPPs and had increased phosphorylation of EGFR and ERK1/2 within the serrated epithelium. Administration of pharmacologic inhibitors of EGFR or MAPK to these transgenic mice significantly reduced polyp development. Activation of EGFR signaling in the intestine of mice promotes development of serrated polyps. EGFR signaling also is activated in human HPPs, sessile serrated adenomas

The potential pitfalls of studying adult sex ratios at aggregate levels in humans.

Science.gov (United States)

Pollet, Thomas V; Stoevenbelt, Andrea H; Kuppens, Toon

2017-09-19

Human adult sex ratios have been studied extensively across the biological and social sciences. While several studies have examined adult sex ratio effects in a multilevel perspective, many studies have focused on effects at an aggregated level only. In this paper, we review some key issues relating to such analyses. We address not only nation-level analyses, but also aggregation at lower levels, to investigate whether these issues extend to lower levels of aggregation. We illustrate these issues with novel databases covering a broad range of variables. Specifically, we discuss distributional issues with aggregated measures of adult sex ratio, significance testing, and statistical non-independence when using aggregate data. Firstly, we show that there are severe distributional issues with national adult sex ratio, such as extreme cases. Secondly, we demonstrate that many 'meaningless' variables are significantly correlated with adult sex ratio (e.g. the max. elevation level correlates with sex ratio at US state level). Finally, we re-examine associations between adult sex ratios and teenage fertility and find no robust evidence for an association at the aggregate level. Our review highlights the potential issues of using aggregate data on adult sex ratios to test hypotheses from an evolutionary perspective in humans.This article is part of the themed issue 'Adult sex ratios and reproductive decisions: a critical re-examination of sex differences in human and animal societies'. © 2017 The Author(s).

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.

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.

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

Nitrosylated hemoglobin levels in human venous erythrocytes correlate with vascular endothelial function measured by digital reactive hyperemia.

Directory of Open Access Journals (Sweden)

Irina I Lobysheva

Full Text Available Impaired nitric oxide (NO-dependent endothelial function is associated with the development of cardiovascular diseases. We hypothesized that erythrocyte levels of nitrosylated hemoglobin (HbNO-heme may reflect vascular endothelial function in vivo. We developed a modified subtraction method using Electron Paramagnetic Resonance (EPR spectroscopy to identify the 5-coordinate α-HbNO (HbNO concentration in human erythrocytes and examined its correlation with endothelial function assessed by peripheral arterial tonometry (PAT. Changes in digital pulse amplitude were measured by PAT during reactive hyperemia following brachial arterial occlusion in a group of healthy volunteers (50 subjects. Erythrocyte HbNO levels were measured at baseline and at the peak of hyperemia. We digitally subtracted an individual model EPR signal of erythrocyte free radicals from the whole EPR spectrum to unmask and quantitate the HbNO EPR signals.Mean erythrocyte HbNO concentration at baseline was 219+/-12 nmol/L (n = 50. HbNO levels and reactive hyperemia (RH indexes were higher in female (free of contraceptive pills than male subjects. We observed a dynamic increase of HbNO levels in erythrocytes isolated at 1-2 min of post-occlusion hyperemia (120+/-8% of basal levels; post-occlusion HbNO levels were correlated with basal levels. Both basal and post-occlusion HbNO levels were significantly correlated with reactive hyperemia (RH indexes (r = 0.58; P<0.0001 for basal HbNO.The study demonstrates quantitative measurements of 5-coordinate α-HbNO in human venous erythrocytes, its dynamic physiologic regulation and correlation with endothelial function measured by tonometry during hyperemia. This opens the way to further understanding of in vivo determinants of NO bioavailability in human circulation.

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.

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....

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....

Linking adult hippocampal neurogenesis with human physiology and disease.

Science.gov (United States)

Bowers, Megan; Jessberger, Sebastian

2016-07-01

We here review the existing evidence linking adult hippocampal neurogenesis and human brain function in physiology and disease. Furthermore, we aim to point out where evidence is missing, highlight current promising avenues of investigation, and suggest future tools and approaches to foster the link between life-long neurogenesis and human brain function. Developmental Dynamics 245:702-709, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

MdHB1 down-regulation activates anthocyanin biosynthesis in the white-fleshed apple cultivar 'Granny Smith'.

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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.

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.

Cerebral time domain-NIRS: reproducibility analysis, optical properties, hemoglobin species and tissue oxygen saturation in a cohort of adult subjects.

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Giacalone, Giacomo; Zanoletti, Marta; Contini, Davide; Re, Rebecca; Spinelli, Lorenzo; Roveri, Luisa; Torricelli, Alessandro

2017-11-01

The reproducibility of cerebral time-domain near-infrared spectroscopy (TD-NIRS) has not been investigated so far. Besides, reference intervals of cerebral optical properties, of absolute concentrations of deoxygenated-hemoglobin (HbR), oxygenated-hemoglobin (HbO), total hemoglobin (HbT) and tissue oxygen saturation (StO 2 ) and their variability have not been reported. We have addressed these issues on a sample of 88 adult healthy subjects. TD-NIRS measurements at 690, 785, 830 nm were fitted with the diffusion model for semi-infinite homogenous media. Reproducibility, performed on 3 measurements at 5 minutes intervals, ranges from 1.8 to 6.9% for each of the hemoglobin species. The mean ± SD global values of HbR, HbO, HbT, StO 2 are respectively 24 ± 7 μM, 33.3 ± 9.5 μM, 57.4 ± 15.8 μM, 58 ± 4.2%. StO 2 displays the narrowest range of variability across brain regions.

[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.

Functional characterization of fetal and adult yak hemoglobins: an oxygen cascade and its molecular basis

DEFF Research Database (Denmark)

Weber, Roy E.; Braunitzer, Gerhard; Lalthantluanga, Ralte

1988-01-01

In contrast to most other mammals, the yak, which is native to high altitudes, has two major fetal and two or four major adult hemoglobin (Hb) components. We report the oxygen affinities and sensitivities to pH and 2,3-diphosphoglycerate of the two fetal and two adult Hbs commonly found in calves...

Performance of HbA1c as an early diagnostic indicator of type 1 diabetes in children and youth.

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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.

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.

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

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.