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Sample records for adult hemoglobin hba

  1. [The hemoglobin of adult Andean condors (Vultur gryphus, Cathartiformes). The amino acid sequence of the major (HbA) and minor component (HbD)].

    PubMed

    Bauer, H; Braunitzer, G; Oberthür, W; Kösters, J; Grimm, F

    1985-12-01

    The complete amino-acid sequence of the alpha A- and the beta-chains of the major component (HbA) and the alpha D- and the beta-chains of the minor component (HbD) of Andean Condor (Vultur gryphus) is presented. The minor component with the alpha D-chains is present in smaller amounts (17%) than in other birds (25%). The comparison with the corresponding chains of Greylag Goose (Anser anser) shows 17 different amino acids (17 nucleotides, only one-point mutations) in the alpha A-chains and 8 (8 nucleotides) in the beta-chains. The alpha D-chains differ from those of the pheasant (Phasanius cholchicus cholchicus) in 24 amino acids (27 nucl., 3 two-point mutations). Seven alpha 1 beta 1-, one alpha 1 beta 2-, three alpha 1 alpha 1-contacts and one beta 1 beta 1-contact are exchanged. The systematy of Cathartiformes, Ciconiiformes and Phoenicopteriformes is discussed, based on the amino-acid exchanges of all known adult hemoglobins of birds.

  2. Glycated Hemoglobin (HbA1c): Clinical Applications of a Mathematical Concept

    PubMed Central

    Leow, Melvin Khee Shing

    2016-01-01

    Background and purpose: Glycated hemoglobin (HbA1c) reflects the cumulative glucose exposure of erythrocytes over a preceding time frame proportional to erythrocyte survival. HbA1c is thus an areal function of the glucose-time curve, an educationally useful concept to aid teaching and clinical judgment. Methods: An ordinary differential equation is formulated as a parsimonious model of HbA1c. The integrated form yields HbA1c as an area-under-the-curve (AUC) of a glucose-time profile. The rate constant of the HbA1c model is then derived using the validated regression equation in the ADAG study that links mean blood glucose and HbA1c with a very high degree of goodness-of-fit. Results: This model has didactic utility to enable patients, biomedical students and clinicians to appreciate how HbA1c may be conceptually inferred from discrete blood glucose values using continuous glucose monitoring system (CGMS) or self-monitored blood glucose (SMBG) glucometer readings as shown in the examples. It can be appreciated how hypoglycemia can occur with rapid HbA1c decline despite poor glycemic control. Conclusions: Being independent of laboratory assay pitfalls, computed ‘virtual’ HbA1c serves as an invaluable internal consistency cross-check against laboratory-measured HbA1c discordant with SMBG readings suggestive of inaccurate/fraudulent glucometer records or hematologic disorders including thalassemia and hemoglobinopathy. This model could be implemented within portable glucometers, CGMS devices and even smartphone apps for deriving tentative ‘virtual’ HbA1c from serial glucose readings as an adjunct to measured HbA1c. Such predicted ‘virtual’ HbA1c readily accessible via glucometers may serve as feedback to modify behavior and empower diabetic patients to achieve better glycemic control. PMID:27708483

  3. Challenges in HbA1c Analysis and Reporting in Patients with Variant Hemoglobins.

    PubMed

    Sultana, T A; Sheme, Z A; Sultana, G S; Sultana, B; Mishu, F A; Khan, N Z; Sarkar, B C; Muttalib, M A; Khan, S A; Choudhury, S; Mahtab, H

    2016-04-01

    Hemoglobin A1c (HbA(1)c) is a well-established indicator of mean glycemia. The presence of genetic variants of hemoglobin can profoundly affect the accuracy of HbA(1)c measurements. Variants of hemoglobin especially Hemoglobin E (HbE) is prevalent in South East Asia including Bangladesh. The objective of our study is to compare the HbA(1)c values measured on high performance liquid chromatography (HPLC) and Turbidimetric Inhibition Immunoassay (TINIA) in diabetic patients with variant hemoglobins including HbE. A total of 7595 diabetic patients receiving treatment at BIRDEM General Hospital were analyzed for HbA(1)c results within a period of two months from December 2013 to January 2014. Seventy two cases out of 7595 (0.95%) had either undetectable or below normal HbA(1)c levels (males-33 and females-39; ratio = 0.82:1) by HPLC method. In 34(0.45%) cases, HbA(1)c value was undetectable by HPLC method but was in the reportable range by TINIA method. In the other 38 (0.55%) cases, HbA(1)c levels were below the reportable range (<4%) by HPLC method but were in the normal or higher range by TINIA method. TINIA method did not agree with HPLC method on Bland Altman plot in the 38 cases with below normal HbA(1)c levels, [Mean bias -5.2(-9.3 to 1.0), 95% CI] but agreed very well [mean bias -0.21 (-0.84 to 0.42), y=1.1037+0.776X; r(2)=0.30, p<0.01] in controls. In control group mean MCV was 83.80±7.48 and in study group was 73.65±10.44. Alkaline electrophoresis confirmed the variant hemoglobin to be HbE. The fasting blood sugar levels of all the 72 cases correlated strongly with TINIA method (r(2) =0.75, p<0.0001) but not with HPLC (r = 0.24, p=0.13). In our regions where populations have a high prevalence of Hb variant, proper knowledge of hemoglobin variants which affect the measurements HbA(1)c level is essential. MCV of 80fl or below may serve as a rough guide to select samples that require analysis by TINIA method. Moreover, HPLC may be a convenient and inexpensive

  4. Luminol chemiluminescence biosensor for glycated hemoglobin (HbA1c) in human blood samples.

    PubMed

    Ahn, Kwang-Soo; Lee, JungHoon; Park, Jong-Myeon; Choi, Han Nim; Lee, Won-Yong

    2016-01-15

    Luminol chemiluminescence (CL) biosensor based on boronic acid modified gold substrate has been developed for the determination of glycated hemoglobin (HbA1c) in human blood samples. In order to selectively capture HbA1c in sample, carboxy-EG6-undecanethiol was self-assembled on a gold thin-film substrate, followed by covalent coupling of 3-aminophenyl boronic acid (3-APBA). The captured HbA1c containing four iron heme groups plays as a catalyst for luminol CL reaction in the presence of hydrogen peroxide, and thus the luminol CL response is linearly proportional to the amount of HbA1c captured on the biosensor surface. The present biosensor showed linear dynamic range of HbA1c from 2.5% to 17.0%, which well covers the clinically important concentration range. In addition, the present biosensor exhibited negligible response to interfering species such as hemoglobin, fructose, and sorbitol. The present HbA1c biosensor was applied to the determination of HbA1c in human blood samples and the results were well agreed with that obtained with a conventional method.

  5. Effect of the N-terminal residues on the quaternary dynamics of human adult hemoglobin

    NASA Astrophysics Data System (ADS)

    Chang, Shanyan; Mizuno, Misao; Ishikawa, Haruto; Mizutani, Yasuhisa

    2016-05-01

    The protein dynamics of human hemoglobin following ligand photolysis was studied by time-resolved resonance Raman spectroscopy. The time-resolved spectra of two kinds of recombinant hemoglobin expressed in Escherichia coli, normal recombinant hemoglobin and the α(V1M)/β(V1M) double mutant, were compared with those of human adult hemoglobin (HbA) purified from blood. A frequency shift of the iron-histidine stretching [ν(Fe-His)] band was observed in the time-resolved spectra of all three hemoglobin samples, indicative of tertiary and quaternary changes in the protein following photolysis. The spectral changes of the α(V1M)/β(V1M) double mutant were distinct from those of HbA in the tens of microseconds region, whereas the spectral changes of normal recombinant hemoglobin were similar to those of HbA isolated from blood. These results demonstrated that a structural change in the N-termini is involved in the second step of the quaternary structure change of hemoglobin. We discuss the implications of these results for understanding the allosteric pathway of HbA.

  6. Effect of low glycemic load diet on glycated hemoglobin (HbA1c) in poorly-controlled diabetes patients.

    PubMed

    Ziaee, Amir; Afaghi, Ahmad; Sarreshtehdari, Majied

    2011-12-29

    Different carbohydrate diets have been administrated to diabetic patients to evaluate the glycemic response, while Poor-controlled diabetes is increasing world wide. To investigate the role of an alternative carbohydrate diet on glycemic control, we explored the effect of a low glycemic load (Low GL)-high fat diet on glycemic response and also glycated hemoglobin (HbA1c) of poor-controlled diabetes patients. Hundred poorly-controlled diabetes patients, HbA1c > 8, age 52.8 ± 4.5 y, were administrated a low GL diet , GL = 67 (Energy 1800 kcal; total fat 36%; fat derived from olive oil and nuts 15%; carbohydrate 42%; protein 22%) for 10 weeks. Patients did their routine life style program during intervention. Fasting blood glucose and HbA1c before and after intervention with significant reduction were: 169 ± 17, 141 ± 12; 8.85% (73 mmol/mol) ± 0.22%, and 7.81% (62 mmol/mol) ± 0.27%; respectively (P < 0.001). Mean fasting blood glucose reduced by 28.1 ± 12.5 and HbA1c by 1.1% (11 mmol/mol) ± 0.3% (P=0.001). There was positive moderate correlation between HbA1c concentration before intervention and FBS reduction after intervention (P < 0.001, at 0.01 level, R =0.52), and strong positive correlation between FBS before intervention and FBS reduction (P < 0.001, at 0.01 level, R = 0.70). This study demonstrated that our alternative low glycemic load diet can be effective in glycemic control.

  7. 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.

    PubMed

    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.

  8. Association between Inflammation and Biological Variation in Hemoglobin A1c in U.S. Nondiabetic Adults

    PubMed Central

    Liu, Shuqian; Hempe, James M.; McCarter, Robert J.; Li, Shengxu

    2015-01-01

    Context: Inflammation is associated with higher glycated hemoglobin (HbA1c) levels. Whether the relationship is independent of blood glucose concentration remains unclear. Objective: The hemoglobin glycation index (HGI) was used to test the hypothesis that interindividual variation in HbA1c is associated with inflammation. Participants: This study used nondiabetic adults from the National Health and Nutrition Examination Survey (1999–2008). Main Outcome Measures: A subsample of participants was used to estimate the linear regression relationship between HbA1c and fasting plasma glucose (FPG). Predicted HbA1c were calculated for 7323 nondiabetic participants by inserting FPG into the equation, HbA1c = 0.017× FPG (mg/dL) + 3.7. HGI was calculated as the difference between the observed and predicted HbA1c and the population was divided into low, moderate, and high HGI subgroups. Polymorphonuclear leukocytes (PMNL), monocytes, and C-reactive protein (CRP) were used as biomarkers of inflammation. Results: Mean HbA1c, CRP, monocyte, and PMNL levels, but not FPG, progressively increased in the low, moderate, and high HGI subgroups. There were disproportionately more Blacks than whites in the high HGI subgroup. CRP (ß, 0.009; 95% confidence interval [CI], 0.0001–0.017), PMNL (ß, 0.036; 95% CI, 0.010–0.062), and monocyte count (ß, 0.072; 95% CI, 0.041–0.104) were each independent predictors of HGI after adjustment for age, sex, race, triglycerides, hemoglobin level, mean corpuscular volume, red cell distribution width, and obesity status. Conclusions: HGI reflects the effects of inflammation on HbA1c in a nondiabetic population of U.S. adults and may be a marker of risk associated with inflammation independent of FPG, race, and obesity. PMID:25867810

  9. Glycated Hemoglobin and Incident Type 2 Diabetes in Singaporean Chinese Adults: The Singapore Chinese Health Study

    PubMed Central

    Bancks, Michael P.; Koh, Woon-Puay; Yuan, Jian-Min; Gross, Myron D.

    2015-01-01

    Background The American Diabetes Association recently included glycated hemoglobin in the diagnostic criteria for diabetes, but research on the utility of this biomarker in Southeast Asians is scant. The aim of this study was to evaluate the association between percent HbA1c and incident diabetes in an Asian population of adult men and women without reported diabetes. Methods Data analysis of 5,770 men and women enrolled in the Singapore Chinese Health Study who provided a blood sample at the follow-up I visit (1999–2004) and had no cancer and no reported history of diabetes or cardiovascular disease events. Diabetes was defined as self-report of physician diagnosis, identified at the follow-up II visit (2006–2010). Results Hazard ratios (and 95% confidence intervals) for incident diabetes by 5 categories of HbA1c were estimated with Cox regression models and continuous HbA1c with cubic spline analysis. Compared to individuals with an HbA1c ≤ 5.7% (≤39 mmol/mol), individuals with HbA1c 5.8–5.9% (40–41 mmol/mol), 6.0–6.1% (42–43 mmol/mol), 6.2–6.4% (44–47 mmol/mol), and ≥ 6.5% (≥48 mmol/mol) had significantly increased risk for incident diabetes during follow-up. In cubic spline analysis, levels below 5.7% HbA1c were not significantly associated with incident diabetes. Conclusions Our study found a strong and graded association with HbA1c 5.8% and above with incident diabetes in Chinese men and women. PMID:25775375

  10. HbA1c overtesting and overtreatment among US adults with controlled type 2 diabetes, 2001-13: observational population based study

    PubMed Central

    Van Houten, Holly K; Ross, Joseph S; Montori, Victor M; Shah, Nilay D

    2015-01-01

    Study question What is the extent and effect of excessive testing for glycated hemoglobin (HbA1c) among adults with controlled type 2 diabetes? Methods A retrospective analysis of data from a national administrative claims database included commercially insured individuals in the USA, 2001-13. Study patients were aged 18 years or older, had type 2 diabetes with stable glycemic control (two consecutive tests showing HbA1c<7.0% within 24 months), did not use insulin, had no history of severe hypoglycemia or hyperglycemia, and were not pregnant. HbA1c testing frequency was measured within 24 months after the second (index) HbA1c test, and classified as guideline recommended (≤2 times/year), frequent (3-4 times/year), and excessive (≥5 times/year). Changes in treatment regimen were ascertained within three months of the index test. Study answer and limitations Of 31 545 patients in the study cohort (mean age 58 years; mean index HbA1c 6.2%), HbA1c testing frequency was excessive in 6% and frequent in 55%. Despite good glycemic control at baseline, treatment was further intensified by addition of glucose lowering drugs or insulin in 8.4% of patients (comprising 13%, 9%, and 7% of those tested excessively, frequently, and per guidelines, respectively; P<0.001). Compared with guideline recommended testing, excessive testing was associated with treatment intensification (odds ratio 1.35 (95% confidence interval 1.22 to 1.50)). Excessive testing rates remained unchanged in 2001-08, but fell significantly after 2009. The odds of excessive testing was 46% lower in 2011 than in 2001-02. The study population is not representative of all US patients with type 2 diabetes because it was restricted to commercially insured adults with stable and controlled diabetes not receiving insulin treatment. The study design did not capture the underuse of HbA1c testing. What this study adds In this US cohort of adults with stable and controlled type 2 diabetes, more than 60% received

  11. [Indicators of glycemic control --hemoglobin A1c (HbA1c), glycated albumin (GA), and 1,5-anhydroglucitol (1,5-AG)].

    PubMed

    Sato, Asako

    2014-01-01

    The clinical goal of diabetes management is a good quality of life that is not different from that of a healthy subjects. To fulfill the goal, prevention of complications is needed under good glycemic control. Although blood glucose measurement is essential for glycemic control, there are diurnal variations in blood glucose levels. An indicator of long-term glycemic control is necessary. HbA1c is the gold standard measurement for the assessment of glycemic control, and worldwide large scale clinical studies of diabetes complications have greatly valued HbA1c as an indicator of glycemic control. In addition, recently, HbA1c was recommended for use in the diagnosis of diabetes in Japan and in the United States. Although HbA1c is used widely and internationally, international standardization of the HbA1c value has not been achieved. In Japan, from April 2014, it has been decided to adopt the National Glycohemoglobin Standardization Program (NGSP) value, which is used by many countries globally, as the first step toward internationalization. Recently, cardiovascular disease in diabetic patients has been increasing in Japan. Relationships between postprandial hyperglycemia and cardiovascular disease have been noted. Therefore, the correction of postprandial hyperglycemia is one of the important goals of glycemic control to prevent cardiovascular disease. HbA1c or glycated albumin (GA) results from the glycation of hemoglobin or serum albumin and represents 2-month or 2-week glycemia, respectively. In addition, the glycation speed of GA is ten times faster than HbA1c, so GA is likely to reflect the variation in blood glucose and postprandial hyperglycemia in combination with HbA1c and its value. 1,5-anhydroglucitol (AG) is a marker of glycemia-induced glycosuria, since reabsorption of filtered 1,5-AG in the proximal tubule is competitively inhibited by glucose. It is an indicator to identify rapid changes in hyperglycemia. Understanding the characteristics of the

  12. Erythropoiesis in the Absence of Adult Hemoglobin

    PubMed Central

    Liu, Shanrun; McConnell, Sean C.

    2013-01-01

    During erythropoiesis, hemoglobin (Hb) synthesis increases from early progenitors to mature enucleated erythrocytes. Although Hb is one of the most extensively studied proteins, the role of Hb in erythroid lineage commitment, differentiation, and maturation remains unclear. In this study, we generate mouse embryos and embryonic stem (ES) cells with all of the adult α and β globin genes deleted (Hb Null). While Hb Null embryos die in midgestation, adult globin genes are not required for primitive or definitive erythroid lineage commitment. In vitro differentiation of Hb Null ES cells generates viable definitive proerythroblasts that undergo apoptosis upon terminal differentiation. Surprisingly, all stages of Hb Null-derived definitive erythroblasts develop normally in vivo in chimeric mice, and Hb Null erythroid cells undergo enucleation to form reticulocytes. Free heme toxicity is not observed in Hb Null-derived erythroblasts. Transplantation of Hb Null-derived bone marrow cells provides short-term radioprotection of lethally irradiated recipients, whose progressive anemia results in an erythroid hyperplasia composed entirely of Hb Null-derived erythroblasts. This novel experimental model system enables the role played by Hb in erythroid cell enucleation, cytoskeleton maturation, and heme and iron regulation to be studied. PMID:23530053

  13. The Electrophoretic Pattern of Hemoglobin in Newborn Babies, and Abnormalities of Hemoglobin F Synthesis in Adults

    PubMed Central

    Vella, F.; Cunningham, T. A.

    1967-01-01

    On routine electrophoretic analyses on filter paper and starch gel in an alkaline or neutral medium, no abnormal hemoglobin fractions were found in the blood of 600 newborn infants or their mothers. Trace amounts of hemoglobin Barts were noted in many of the blood samples from newborns when the starch gels (phosphate buffer pH 7.0) were stained with a benzidine/H2O2 reagent. In one infant, precocious cessation of synthesis of hemoglobin F was postulated to account for the small amounts of this hemoglobin found in a cord-blood specimen. Analysis of 15,000 blood samples from adults revealed two instances in which the hemoglobin F level was 20 and 35%, respectively. The former was attributed to a hereditary persistence of hemoglobin F, while the latter was associated with acute leukemia. In an addendum, the finding of an infant with an abnormal hemoglobin variant, resembling in many of its properties hemoglobin F Texas, is reported. ImagesFig. 1Fig. 2 PMID:6019054

  14. Association of HbA1c and cardiovascular and renal disease in an adult Mediterranean population

    PubMed Central

    2013-01-01

    Background Increasing evidence suggests a mechanistic link between the glycemic environment and renal and cardiovascular events, even below the threshold for diabetes. We aimed to assess the association between HbA1c and chronic kidney disease (CKD) and cardiovascular disease (CVD). Methods A cross-sectional study involving a random representative sample of 2270 adults from southern Spain (Malaga) was undertaken. We measured HbA1c, serum creatinine and albuminuria in fasting blood and urine samples. Results Individuals without diabetes in the upper HbA1c tertile had an unfavorable cardiovascular and renal profile and shared certain clinical characteristics with the patients with diabetes. Overall, a higher HbA1c concentration was strongly associated with CKD or CVD after adjustment for traditional risk factors. The patients with known diabetes had a 2-fold higher odds of CKD or CVD. However, when both parameters were introduced in the same model, the HbA1c concentration was only significantly associated with clinical endpoints (OR: 1.4, 95% CI, 1.1-1.6, P = 0.002). An increase in HbA1c of one percentage point was associated with a 30% to 40% increase in the rate of CKD or CVD. This relationship was apparent in persons with and without known diabetes. ROC curves illustrated that a HbA1c of 37 mmol/mol (5.5%) was the optimal value in terms of sensitivity and specificity for predicting endpoints in this population. Conclusion HbA1c levels were associated with a higher prevalence of CKD and CVD cross-sectionally, regardless of diabetes status. These data support the value of HbA1c as a marker of cardiovascular and renal disease in the general population. PMID:23865389

  15. Association Between the Presence of Iron Deficiency Anemia and Hemoglobin A1c in Korean Adults

    PubMed Central

    Hong, Jae W.; Ku, Cheol R.; Noh, Jung H.; Ko, Kyung S.; Rhee, Byoung D.; Kim, Dong-Jun

    2015-01-01

    Abstract Few studies have investigated the clinical effect of iron deficiency anemia (IDA) on the use of the Hemoglobin A1c (HbA1c) as a screening parameter for diabetes or prediabetes. We investigated the association between IDA and HbA1c levels in Korean adults. Among the 11,472 adults (≥19 years of age) who participated in the 2011–2012 Korea National Health and Nutrition Examination Survey (a cross-sectional and nationally representative survey conducted by the Korean Center for Disease Control for Health Statistics), 807 patients with diabetes currently taking anti-diabetes medications were excluded from this study. We compared the weighted HbA1c levels and weighted proportion (%) of HbA1c levels of ≥5.7%, ≥6.1%, and ≥6.5% according to the range of fasting plasma glucose (FPG) levels and the presence of IDA. Among 10,665 participants (weighted n = 35,229,108), the prevalence of anemia and IDA was 7.3% and 4.3%, respectively. The HbA1c levels were higher in participants with IDA (5.70% ± 0.02%) than in normal participants (5.59% ± 0.01%; P < 0.001), whereas there was no significant difference in FPG levels. In participants with an FPG level of <100 mg/dL and 100 to 125 mg/dL, the weighted HbA1c level was higher in those with IDA (5.59% ± 0.02% and 6.00% ± 0.05%) than in normal participants (5.44% ± 0.01% and 5.82% ± 0.01%) after adjusting for confounders such as age, sex, FPG level, heavy alcohol drinking, waist circumference, and smoking status as well as after exclusion of an estimated glomerular filtration rate of <60 mL/min/1.73 m2 (P < 0.001, <0.01). The weighted proportions (%) of an HbA1c level of ≥5.7% and ≥6.1% were also higher in participants with IDA than in normal participants (P < 0.001, <0.05). However, the weighted HbA1c levels in individuals with an FPG level ≥126 mg/dL and a weighted proportion (%) of an HbA1c level of ≥6.5% showed no significant differences according to

  16. Hemoglobin

    MedlinePlus

    ... AACC products and services. Advertising & Sponsorship: Policy | Opportunities Hemoglobin Share this page: Was this page helpful? Also known as: Hgb; Hb; H and H (Hemoglobin and Hematocrit) Formal name: Hemoglobin Related tests: Complete ...

  17. Increased nitrite reductase activity of fetal versus adult ovine hemoglobin

    PubMed Central

    Blood, Arlin B.; Tiso, Mauro; Verma, Shilpa T.; Lo, Jennifer; Joshi, Mahesh S.; Azarov, Ivan; Longo, Lawrence D.; Gladwin, Mark T.; Kim-Shapiro, Daniel B.; Power, Gordon G.

    2009-01-01

    Growing evidence indicates that nitrite, NO2−, serves as a circulating reservoir of nitric oxide (NO) bioactivity that is activated during physiological and pathological hypoxia. One of the intravascular mechanisms for nitrite conversion to NO is a chemical nitrite reductase activity of deoxyhemoglobin. The rate of NO production from this reaction is increased when hemoglobin is in the R conformation. Because the mammalian fetus exists in a low-oxygen environment compared with the adult and is exposed to episodes of severe ischemia during the normal birthing process, and because fetal hemoglobin assumes the R conformation more readily than adult hemoglobin, we hypothesized that nitrite reduction to NO may be enhanced in the fetal circulation. We found that the reaction was faster for fetal than maternal hemoglobin or blood and that the reactions were fastest at 50–80% oxygen saturation, consistent with an R-state catalysis that is predominant for fetal hemoglobin. Nitrite concentrations were similar in blood taken from chronically instrumented normoxic ewes and their fetuses but were elevated in response to chronic hypoxia. The findings suggest an augmented nitrite reductase activity of fetal hemoglobin and that the production of nitrite may participate in the regulation of vascular NO homeostasis in the fetus. PMID:19028797

  18. Relationship of Hemoglobin Concentration in Adult Asthmatic Patients.

    PubMed

    Nasreen, S; Nessa, A; Islam, M F; Husain, M F; Khatun, N; Wahed, F; Zannat, M R; Tajkia, T

    2016-10-01

    Asthma is a chronic inflammatory disorder of the airways, in which many cells and cellular elements play a role. Asthma is one of the most common diseases globally and currently affects 300 million people. The epidemic rise in anemia, asthma, and related allergic disease is a common major public health problem worldwide. Asthma and anemia associated with acute infections occur both in children and adults. This descriptive type of cross sectional study was done to find out the levels of hemoglobin concentration in adult asthmatic patients and carried out in the Department of Physiology, Mymensingh Medical College, Mymensingh, Bangladesh from July 2014 to January 2016. Fifty (50) male and 50 (fifty) female adult asthmatic patients aged 18-60 years were included in the study group. They are enrolled from the Department of Medicine, Mymensingh Medical College, Mymensingh, Bangladesh and also from locality. For comparison age matched 50 male and 50 female apparently healthy persons were also studied as control. Hemoglobin concentration was estimated by Cyanmethemoglobin method. For statistical analysis unpaired student's 't' test was used. Mean hemoglobin concentration was significantly decreased in study group in comparison to control group and the result was statistically significant (p<0.001). The study findings showed a high prevalence of anemia among asthmatic patients than non asthmatic healthy persons.

  19. Determination of the value of glycated hemoglobin HbA1c and fructosamine in assessing the risk of perioperative complications after cardiac surgery in patients with type 2 diabetes

    PubMed Central

    Wróbel, Marta; Rokicka, Dominika; Szymborska-Kajanek, Aleksandra; Foremny, Jerzy; Nadziakiewicz, Paweł; Zembala, Marian; Strojek, Krzysztof

    2016-01-01

    Introduction Patients with diabetes have a worse postoperative course and longer length of hospital stay after surgery. A good indicator of proper long-term (3 months) glycemic control is glycated hemoglobin (HbA1c), and fructosamine in the short term (2–3 weeks). Aim To determine the degree of glycemic control evaluated preoperatively by HbA1c and/or fructosamine influence on the postoperative course of patients with diabetes undergoing coronary artery bypass grafting (CABG) in 2014–2015. Material and methods Before the operation HbA1c (N < 7.0) and fructosamine (N < 280 µmol/l) were measured and depending on the results the respondents were divided into 4 groups: group I (n = 46) – normal both parameters; group II (n = 22) – high both values; group III (n = 4) – normal fructosamine/HbA1c high; group IV (n = 33) – high HbA1c/fructosamine normal. Statistical analysis was performed using the t-test assuming p < 0.05 to be statistically significant. Results One hundred and five patients were treated by CABG/OPCAB (39 female, 66 males). The mean age was 65.7 ±7.3, HbA1c: 7.23 ±1.2%, fructosamine: 261.8 ±43.8. There was no difference in the incidence of other postoperative complications between the two groups. Conclusions Glycated hemoglobin and fructosamine levels to a similar extent define the risk of perioperative complications in patients undergoing cardiac surgery. In patients in whom there is a need to quickly compensate for elevated blood glucose consider enabling determination of fructosamine. PMID:28096825

  20. Differential expression of murine adult hemoglobins in early ontogeny

    SciTech Connect

    Wawrzyniak, C.J.; Lewis, S.E.; Popp, R.A.

    1985-01-01

    A hemoglobin mutation is described that permits study of the expression of the two adult ..beta..-globin genes throughout fetal and postnatal development. Mice with a mutation at the Hbb/sup s/, ..beta..-globin locus, were used to study the relative levels of ..beta..-s2major and ..beta..-sminor globins specified by the mutant Hbb/sup s2/ haplotype during development. At 11.5 days of gestation ..beta..-sminor comprised over 80% and ..beta..-s2major under 20% of the adult beta-globin. The relative level of ..beta..-sminor decreased through fetal development; at birth ..beta..-sminor represented 33.7% of the ..beta..-globin. The adult values of 71.0% ..beta..-s2major and 29.0% ..beta..-sminor globin are expressed in mice six days after birth. Because the two ..beta..-globin genes are expressed in mice of the Hbb/sup 2s/ haplotype, both the ..beta..-smajor and ..beta..-sminor genes must be expressed in mice of the Hbb/sup s/ haplotype. Expression of the ..beta..-sminor gene is elevated to 35.6% in Hbb/sup s2/ mice that have been bled repeatedly. Thus, the 5' ..beta..-s2major and 3' ..beta..-sminor genes of the Hbb/sup s2/ haplotype and, presumably the 5' ..beta..-smajor and 3' ..beta..-sminor genes of the Hbb/sup s/ haplotype, are regulated independently and are homologous to the 5' ..beta..-dmajor and 3' ..beta..-dminor genes of the Hbb/sup d/ haplotype. Mice of the Hbb/sup s2/ haplotype are better than mice of the Hbb/sup d/ haplotytpe for studying the mechanisms of hemoglobin switching because the Hbb/sup s2/ each of the three embryonic and two adult hemoglobins can be separated by electrophoresis. 17 refs., 3 figs.

  1. Evidence for Association between SH2B1 Gene Variants and Glycated Hemoglobin in Nondiabetic European American Young Adults: The Add Health Study.

    PubMed

    Lange, Leslie A; Graff, Mariaelisa; Lange, Ethan M; Young, Kristin L; Richardson, Andrea S; Mohlke, Karen L; North, Kari E; Harris, Kathleen M; Gordon-Larsen, Penny

    2016-09-01

    Glycated hemoglobin (HbA1c) is used to classify glycaemia and type 2 diabetes (T2D). Body mass index (BMI) is a predictor of HbA1c levels and T2D. We tested 43 established BMI and obesity loci for association with HbA1c in a nationally representative multiethnic sample of young adults from the National Longitudinal Study of Adolescent to Adult Health [Add Health: age 24-34 years; n = 5641 European Americans (EA); 1740 African Americans (AA); 1444 Hispanic Americans (HA)] without T2D, using two levels of covariate adjustment (Model 1: age, sex, smoking, and geographic region; Model 2: Model 1 covariates plus BMI). Bonferroni adjustment was made for 43 SNPs and we considered P < 0.0011 statistically significant. Means (SD) for HbA1c were 5.4% (0.3) in EA, 5.7% (0.4) in AA, and 5.5% (0.3) in HA. We observed significant evidence for association with HbA1c for two variants near SH2B1 in EA (rs4788102, P = 2.2 × 10(-4) ; rs7359397, P = 9.8 × 10(-4) ) for Model 1. Both results were attenuated after adjustment for BMI (rs4788102, P = 1.7 × 10(-3) ; rs7359397, P = 4.6 × 10(-3) ). No variant reached Bonferroni-corrected significance in AA or HA. These results suggest that SH2B1 polymorphisms are associated with HbA1c, largely independent of BMI, in EA young adults.

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

    PubMed

    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.

  3. Hb Lake Tapawingo [α46(CE4)Phe→Ser; HBA2:c.140T>C]: a new unstable α chain hemoglobin variant associated with low systemic arterial saturation.

    PubMed

    Guest, Erin M; Neville, Kathleen A; Hoyer, James D; Safo, Martin K; Garg, Uttam; Saunders, Carol J; Abdulmalik, Osheiza; Zwick, David L

    2011-01-01

    A new unstable α-globin variant was detected in a child with hypoxemia and anemia. The child's mother was found to carry the same mutation. The hemoglobin (Hb) variant co-eluted with Hb A(2) by cation exchange high performance liquid chromatography (HPLC) and appeared cathodal to Hb A and anodal to Hb F by isoelectric focusing. It represented less than 20% of the total Hb and was unstable by isopropanol testing. Gene sequencing identified a missense mutation on the α2 gene [HBA2:c.140T>C]. Oxygen dissociation and P(50) test results were normal.

  4. Association of Exposure to Radio-Frequency Electromagnetic Field Radiation (RF-EMFR) Generated by Mobile Phone Base Stations with Glycated Hemoglobin (HbA1c) and Risk of Type 2 Diabetes Mellitus.

    PubMed

    Meo, Sultan Ayoub; Alsubaie, Yazeed; Almubarak, Zaid; Almutawa, Hisham; AlQasem, Yazeed; Hasanato, Rana Muhammed

    2015-11-13

    Installation of mobile phone base stations in residential areas has initiated public debate about possible adverse effects on human health. This study aimed to determine the association of exposure to radio frequency electromagnetic field radiation (RF-EMFR) generated by mobile phone base stations with glycated hemoglobin (HbA1c) and occurrence of type 2 diabetes mellitus. For this study, two different elementary schools (school-1 and school-2) were selected. We recruited 159 students in total; 96 male students from school-1, with age range 12-16 years, and 63 male students with age range 12-17 years from school-2. Mobile phone base stations with towers existed about 200 m away from the school buildings. RF-EMFR was measured inside both schools. In school-1, RF-EMFR was 9.601 nW/cm² at frequency of 925 MHz, and students had been exposed to RF-EMFR for a duration of 6 h daily, five days in a week. In school-2, RF-EMFR was 1.909 nW/cm² at frequency of 925 MHz and students had been exposed for 6 h daily, five days in a week. 5-6 mL blood was collected from all the students and HbA1c was measured by using a Dimension Xpand Plus Integrated Chemistry System, Siemens. The mean HbA1c for the students who were exposed to high RF-EMFR was significantly higher (5.44 ± 0.22) than the mean HbA1c for the students who were exposed to low RF-EMFR (5.32 ± 0.34) (p = 0.007). Moreover, students who were exposed to high RF-EMFR generated by MPBS had a significantly higher risk of type 2 diabetes mellitus (p = 0.016) relative to their counterparts who were exposed to low RF-EMFR. It is concluded that exposure to high RF-EMFR generated by MPBS is associated with elevated levels of HbA1c and risk of type 2 diabetes mellitus.

  5. Association of Exposure to Radio-Frequency Electromagnetic Field Radiation (RF-EMFR) Generated by Mobile Phone Base Stations with Glycated Hemoglobin (HbA1c) and Risk of Type 2 Diabetes Mellitus

    PubMed Central

    Meo, Sultan Ayoub; Alsubaie, Yazeed; Almubarak, Zaid; Almutawa, Hisham; AlQasem, Yazeed; Muhammed Hasanato, Rana

    2015-01-01

    Installation of mobile phone base stations in residential areas has initiated public debate about possible adverse effects on human health. This study aimed to determine the association of exposure to radio frequency electromagnetic field radiation (RF-EMFR) generated by mobile phone base stations with glycated hemoglobin (HbA1c) and occurrence of type 2 diabetes mellitus. For this study, two different elementary schools (school-1 and school-2) were selected. We recruited 159 students in total; 96 male students from school-1, with age range 12–16 years, and 63 male students with age range 12–17 years from school-2. Mobile phone base stations with towers existed about 200 m away from the school buildings. RF-EMFR was measured inside both schools. In school-1, RF-EMFR was 9.601 nW/cm2 at frequency of 925 MHz, and students had been exposed to RF-EMFR for a duration of 6 h daily, five days in a week. In school-2, RF-EMFR was 1.909 nW/cm2 at frequency of 925 MHz and students had been exposed for 6 h daily, five days in a week. 5–6 mL blood was collected from all the students and HbA1c was measured by using a Dimension Xpand Plus Integrated Chemistry System, Siemens. The mean HbA1c for the students who were exposed to high RF-EMFR was significantly higher (5.44 ± 0.22) than the mean HbA1c for the students who were exposed to low RF-EMFR (5.32 ± 0.34) (p = 0.007). Moreover, students who were exposed to high RF-EMFR generated by MPBS had a significantly higher risk of type 2 diabetes mellitus (p = 0.016) relative to their counterparts who were exposed to low RF-EMFR. It is concluded that exposure to high RF-EMFR generated by MPBS is associated with elevated levels of HbA1c and risk of type 2 diabetes mellitus. PMID:26580639

  6. Association between Alcohol Intake and Hemoglobin A1c in the Korean Adults: The 2011-2013 Korea National Health and Nutrition Examination Survey

    PubMed Central

    Hong, Jae Won; Noh, Jung Hyun; Kim, Dong-Jun

    2016-01-01

    Background Although alcohol consumption is commonly encountered in clinical practice, few studies have investigated the clinical significance of alcohol intake on the use of the hemoglobin A1c (HbA1c) level. Objectives This study was performed to investigate the association between alcohol intake and HbA1c level in the general population. Methods Among the 24,594 participants who participated in the 2011–2013 Korea National Health and Nutrition Examination Survey (KNHANES), 12,923 participants were analyzed in this study. We excluded diabetic patients currently taking antidiabetes medication. We compared the HbA1c level and proportions of patients with an HbA1c level of ≥5.7%, ≥6.1%, and ≥6.5% according to the fasting plasma glucose (FPG) concentration range and the amount of alcohol intake. The average amounts of daily alcohol intake were categorized into three groups: 0 g/day, <30 g/day, ≥30 g/day. Results The mean HbA1c level was 5.65%, and the mean FPG concentration was 95.3 mg/dl. The percentages of patients with an HbA1c level of ≥5.7%, ≥6.1%, and ≥6.5% were 42.6%, 13.4%, and 4.5%, respectively. The average amount of alcohol intake was 12.3 g/day. The percentages of subjects with alcohol intake 0, <30, and ≥ 30 g/day were 16.5%, 69.7%, and 13.8%, respectively. There was a significant positive relationship between alcohol intake and FPG concentration (P < 0.001), the prevalence of impaired fasting glucose (P < 0.001), and the prevalence of diabetes (P < 0.001). However, there was no significant relationship between the alcohol intake and HbA1c level. Overall, the adjusted HbA1c levels decreased across alcohol intake (5.70% ± 0.01%, 5.66% ± 0.01%, and 5.55% ± 0.01%) after adjustment for confounding factors such as age, sex, FPG concentration, college graduation, smoking history, presence of hypertension, waist circumference, serum total cholesterol concentration, serum high-density lipoprotein cholesterol concentration, serum triglyceride

  7. A novel hemoglobin variant found on the α1 chain: Hb KSVGH (HBA1: p.Lys57_Gly58insSerHisGlySerAlaGlnValLys).

    PubMed

    Wang, Mei-Chun; Tsai, Kuo-Wang; Chu, Chih-Hsun; Yu, Ming-Sun; Lam, Hing-Chung

    2015-01-01

    Glycosylated hemoglobin (Hb A1C) is a crucial indicator for the long-term control and the diagnosis of diabetes. However, the presence of hemoglobin (Hb) variants may affect the measured value of Hb A1C and result in an abnormal graph trend and inconsistency between the clinical blood sugar test and Hb A1C values. In this study, laboratory data of 41,267 patients with diabetes were collected. The Hb A1C levels and the graph results were examined. We identified 74 cases containing abnormal Hb A1C graph trends. The conducted blood cell counts and capillary Hb electrophoresis were used to analyze Hb variants. We also determined gene variation for the Hb variants by a sequence approach. Fifteen different types of Hb variants were identified in this study. Among these, we found a novel variant in which the α1 subunit of Hb showed an insertion of 24 nucleotides (nts) between the 56th and 57th residues. We named this novel variant Hb Kaohsiung Veterans General Hospital (Hb KSVGH) (HBA1: p.Lys57_Gly58insSerHisGlySerAlaGlnValLys).

  8. Implications of iron deficiency/anemia on the classification of diabetes using HbA1c

    PubMed Central

    Attard, S M; Herring, A H; Wang, H; Howard, A-G; Thompson, A L; Adair, L S; Mayer-Davis, E J; Gordon-Larsen, P

    2015-01-01

    Background/Objectives: Nonglycemic factors like iron deficiency (ID) or anemia may interfere with classification of diabetes and prediabetes using hemoglobin A1c (HbA1c). However, few population-based studies of diabetes in areas with endemic ID/anemia have been conducted. We aimed to determine how mutually exclusive categories of ID alone, anemia alone and iron-deficiency anemia (IDA) were each associated with prediabetes and diabetes prevalence using fasting blood glucose (FBG) versus HbA1c in a population-based study of adults with endemic ID/anemia. Subjects/Methods: We used data from the China Health and Nutrition Survey, a longitudinal, population-based study across 228 communities within nine provinces of China. This analysis included 7308 adults seen in the 2009 survey aged 18–75 years. We used descriptive and covariate-adjusted models to examine relative risk of prediabetes and diabetes using FBG alone, HbA1c alone, HbA1c and FBG, or neither (normoglycemia) by anemia alone, ID alone, IDA or normal iron/hemoglobin. Results: Approximately 65% of individuals with diabetes in our sample were concordantly classified with diabetes using both FBG and HbA1c, while 35% had a discordant diabetes classification: they were classified using either FBG or HbA1c, but not both. Fewer participants with ID alone versus normal iron/hemoglobin were classified with diabetes using HbA1c only. From covariate-adjusted, multinomial regression analyses, the adjusted prevalence of prediabetes using HbA1c only was 22% for men with anemia alone, but 13% for men with normal iron/hemoglobin. In contrast, the predicted prevalence of prediabetes using HbA1c only was 8% for women with ID alone, compared with 13% for women with normal iron/hemoglobin. Conclusions: These findings suggest potential misclassification of diabetes using HbA1c in areas of endemic ID/anemia. Estimating diabetes prevalence using HbA1c may result in under-diagnosis in women with ID and over-diagnosis in men with

  9. Interference of the Hope Hemoglobin With Hemoglobin A1c Results.

    PubMed

    Chakraborty, Sutirtha; Chanda, Dalia; Gain, Mithun; Krishnan, Prasad

    2015-01-01

    Hemoglobin A1c (HbA1c) is now considered to be the marker of choice in diagnosis and management of diabetes mellitus, based on the results of certain landmark clinical trials. Herein, we report the case of a 52-year-old ethnic Southeast Asian Indian man with impaired glucose tolerance whose glycated hemoglobin (ie, HbA1c) levels, as measured via Bio-Rad D10 high-performance liquid chromatography (HPLC) and Roche Tina-quant immunoassay were 47.8% and 44.0%, respectively. No variant hemoglobin (Hb) peak was observed via the D10 chromatogram. We assayed the patient specimen on the Sebia MINICAP capillary electrophoresis platform; the HbA1c level was 6.8%, with a large variant Hb peak of 42.0%. This finding suggested the possible presence of the heterozygous Hb Hope, which can result in spuriously elevated HbA1c results on HPLC and turbidimetric immunoassays. Although the capillary electrophoresis system was able to identify the variant, the A1c results should not be considered accurate due to overlapping of the variant and adult Hb peaks on the electrophoretogram reading. Hb Hope is usually clinically silent but can present such analytical challenges. Through this case study, we critically discuss the limitations of various HbA1c assay methods, highlighting the fact that laboratory professionals need to be aware of occurrences of Hb Hope, to help ensure patient safety.

  10. HMGA2 Moderately Increases Fetal Hemoglobin Expression in Human Adult Erythroblasts

    PubMed Central

    de Vasconcellos, Jaira F.; Lee, Y. Terry; Byrnes, Colleen; Tumburu, Laxminath; Rabel, Antoinette; Miller, Jeffery L.

    2016-01-01

    Induction of fetal hemoglobin (HbF) has therapeutic importance for patients with beta-hemoglobin disorders. Previous studies showed that let-7 microRNAs (miRNAs) are highly regulated in erythroid cells during the fetal-to-adult developmental transition, and that targeting let-7 mediated the up-regulation of HbF to greater than 30% of the total globin levels in human adult cultured erythroblasts. HMGA2 is a member of the high-mobility group A family of proteins and a validated target of the let-7 family of miRNAs. Here we investigate whether expression of HMGA2 directly regulates fetal hemoglobin in adult erythroblasts. Let-7 resistant HMGA2 expression was studied after lentiviral transduction of CD34(+) cells. The transgene was regulated by the erythroid-specific gene promoter region of the human SPTA1 gene (HMGA2-OE). HMGA2-OE caused significant increases in gamma-globin mRNA expression and HbF to around 16% of the total hemoglobin levels compared to matched control transductions. Interestingly, no significant changes in KLF1, SOX6, GATA1, ZBTB7A and BCL11A mRNA levels were observed. Overall, our data suggest that expression of HMGA2, a downstream target of let-7 miRNAs, causes moderately increased gamma-globin gene and protein expression in adult human erythroblasts. PMID:27861570

  11. Perioperative Hemoglobin Trajectory in Adult Cardiac Surgical Patients

    PubMed Central

    Scott, David A.; Tung, Hon-Ming Andrew; Slater, Reuben

    2015-01-01

    Abstract: Preoperative anemia and nadir hemoglobin (Hb) during cardiopulmonary bypass (CPB) have been identified as significant risk factors for blood transfusion during cardiac surgery. The aim of this study was to confirm the association between preoperative anemia, perioperative fluid management, and blood transfusion. In addition, the proportion of elective cardiac surgery patients presenting for surgery with anemia was identified to examine whether the opportunity exists for timely diagnosis and intervention. Data from referral until hospital discharge were comprehensively reviewed over a 12-month period for all nonemergency cardiac surgical patients operated on in our institution. Of the 342 patients identified, elective cases were referred a median of 35 days before preoperative clinic and operated on a median of 14 days subsequently. Subacute cases had a median of 3 days from referral to surgery. As per the World Health Organization (WHO) criteria for anemia, 24.2% of elective and 29.6% of subacute patients were anemic. Blood transfusion was administered to 46.2% of patients during their admission. Transfusion was more likely in patients who were female (odds ratio [OR]: 2.45, 95%confidence interval [CI]: 1.28–4.70), had a low body mass index (BMI) (OR: .89, 95% CI: .84–.94), preoperative anemia (OR: 5.15, 95% CI: 2.59–10.24), or renal impairment (OR: 5.44, 95% CI: 2.42–12.22). Hemodilution minimization strategies reduced the Hb fall during CPB, but not transfusion rates. This study identifies a high prevalence of preoperative anemia with sufficient time for elective referrals to undergo appropriate diagnosis and interventions. It also confirms that low red cell mass (anemia and low BMI) and renal impairment are predictors of perioperative blood transfusion. Perfusion strategies to reduce hemodilution are effective at minimizing the intraoperative fall in Hb concentration but did not influence transfusion rate. PMID:26543251

  12. Adult, embryonic and fetal hemoglobin are expressed in human glioblastoma cells.

    PubMed

    Emara, Marwan; Turner, A Robert; Allalunis-Turner, Joan

    2014-02-01

    Hemoglobin is a hemoprotein, produced mainly in erythrocytes circulating in the blood. However, non-erythroid hemoglobins have been previously reported in other cell types including human and rodent neurons of embryonic and adult brain, but not astrocytes and oligodendrocytes. Human glioblastoma multiforme (GBM) is the most aggressive tumor among gliomas. However, despite extensive basic and clinical research studies on GBM cells, little is known about glial defence mechanisms that allow these cells to survive and resist various types of treatment. We have shown previously that the newest members of vertebrate globin family, neuroglobin (Ngb) and cytoglobin (Cygb), are expressed in human GBM cells. In this study, we sought to determine whether hemoglobin is also expressed in GBM cells. Conventional RT-PCR, DNA sequencing, western blot analysis, mass spectrometry and fluorescence microscopy were used to investigate globin expression in GBM cell lines (M006x, M059J, M059K, M010b, U87R and U87T) that have unique characteristics in terms of tumor invasion and response to radiotherapy and hypoxia. The data showed that α, β, γ, δ, ζ and ε globins are expressed in all tested GBM cell lines. To our knowledge, we are the first to report expression of fetal, embryonic and adult hemoglobin in GBM cells under normal physiological conditions that may suggest an undefined function of those expressed hemoglobins. Together with our previous reports on globins (Ngb and Cygb) expression in GBM cells, the expression of different hemoglobins may constitute a part of series of active defence mechanisms supporting these cells to resist various types of treatments including chemotherapy and radiotherapy.

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

    PubMed

    Takahashi, Eiko; Moriyama, Kengo; Yamakado, Minoru

    2014-06-01

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

  14. Independent association of HbA(1c) and incident cardiovascular disease in people without diabetes.

    PubMed

    Adams, Robert J; Appleton, Sarah L; Hill, Catherine L; Wilson, David H; Taylor, Anne W; Chittleborough, Catherine R; Gill, Tiffany K; Ruffin, Richard E

    2009-03-01

    Recent studies have reported no association between elevated glycated hemoglobin (HbA(1c)) and incident cardiovascular disease (CVD) among women without diabetes. This study describes associations between HbA(1c) and new onset CVD in a representative adult population cohort. Assessment of participants in The North West Adelaide Health Study (NWAHS), a population study of randomly selected adults (age > or =18 years, n = 4,060), included measurement of height, weight, blood pressure, fasting lipids, glucose, and HbA(1c). A self-completed questionnaire assessed doctor-diagnosed diabetes, CVD and stroke, smoking status, and demographics. The cohort was followed for an average 3.5 years. Of the 2,913 adults free of diabetes at baseline and follow-up, 94 (3.5%) reported new onset coronary heart disease (CHD) and/or stroke. Compared with those with an HbA(1c) < or =5.0%, risk of new onset CVD was increased in those with HbA(1c) 5.4-5.6% (odds ratio (OR) 2.5, 95% confidence interval (CI) 1.4, 4.6), and > or =5.7% (OR 1.9, 95% CI 1.1, 3.4), after adjustment for other risk factors. The association was stronger in women than men (P = 0.03), and attenuated to only a small degree by addition of impaired fasting glucose (IFG), hypertension, hypercholesterolemia, BMI, waist circumference, or smoking to the model. Elevated HbA(1c) is related to new onset CVD over a relatively short follow-up period in both men and women without diabetes and who do not develop diabetes, after adjustment for other major risk factors. Unlike previous studies, this relationship was not substantially attenuated by other traditional risk factors.

  15. Relationship between hemoglobin levels and risk for suspected non-alcoholic fatty liver in Taiwanese adults.

    PubMed

    Bai, Chyi-Huey; Wu, Ming-Shun; Owaga, Eddy; Cheng, Shu-Yu; Pan, Wen-Harn; Chang, Jung-Su

    2014-10-31

    Body iron levels have recently been shown to be a strong predictor for non-alcoholic fatty liver disease (NAFLD). The aims of this study were to investigate the prevalence of NAFLD in a general adult population, and to investigate the relationship between body iron levels, NAFLD and the metabolic syndrome (MetS). 2186 adults participated in the third National Nutrition and Health Survey in Taiwan (NAHSIT, 2005-2008). The participants underwent anthropometry measurements and phlebotomy after an overnight fast, and those with excessive alcohol intake, iron overload of serum ferritin > 600 ng/ml, hepatitis viral infection and hepatocellular carcinoma were excluded. Suspected NAFLD was diagnosed by three alanine transaminase (ALT) cut-points: cut-point 1: serum ALT > 40 U/l; cut-point 2: ALT ≥ 25 U/l for male and ALT ≥ 17 U/l for female; and cut-point 3: ALT ≥ 35 U/l for male and ALT ≥ 26 U/l for female. The prevalence proportion of suspected NAFLD among Taiwanese adults was 6.6% (cut-point 1), 36% (cut-point 2); and 14.3% (cut-point 3). Body iron levels were significantly higher in individuals with suspected NAFLD compared with those without. Distribution of hemoglobin levels, but not serum ferritin levels, by decade of age showed strong correlation with the prevalence of suspected NAFLD in individuals with MetS. Multivariate adjusted odds ratio (OR) showed that the best predictors for suspected NAFLD with the MetS were hemoglobin [OR 1.43 (1.21-1.68); P < 0.0001] and hyperlipidemia [OR 1.52 (1.19-1.94); P = 0.0007]. In individuals without MetS, the adjusted OR of suspected NAFLD was markedly higher for hemoglobin [OR 1.25 (1.12-1.41); P < 0.0001]. In conclusion, adults with high hemoglobin levels (14.4 μg/dl for male and 13.2 μg/dl for female) are at the greatest risk for developing abnormal liver function. Hemoglobin test should be considered as a part of clinical evaluation for patients with NAFLD.

  16. Higher minor hemoglobin A2 levels in multiple sclerosis patients correlate with lesser disease severity

    PubMed Central

    Ozcan, Muhammed Emin; Ince, Bahri; Karadeli, Hasan Huseyin; Gedikbasi, Asuman; Asil, Talip; Altinoz, Meric A

    2016-01-01

    Objective To define whether minor adult hemoglobin A2 (HbA2, α2δ2) exerts any protective activity in multiple sclerosis (MS). Methods HbA2 levels were measured in 146 MS patients with high performance liquid chromatography and association with MS Severity Scores (MSSS) were determined. HbA2 associations with blood count parameters were also studied using blood counts evaluated on the same day of high performance liquid chromatography sampling. Routine biochemical parameters were also determined to rule out elusively influential factors, such as anemia and thyroid disorders. Results HbA2 levels negatively correlated with MSSS (Spearman correlation, R: −0.186, P=0.025). Exclusion of confounding factors with a generalized linear model revealed an even stronger negative correlation between HbA2 and MSSS (P<0.001). HbA2 positively correlated with red blood cells (RBCs) (R=0.350, P<0.001) and in turn, RBCs negatively correlated with MSSS (R=−0.180, P=0.031). Average HbA2 levels were highest among patients treated with interferon β1a. Conclusion RBC fragility is increased in MS, and recent data suggest that circulating free Hb contributes to neural injury in MS. HbA2 and its oxidative denaturation product hemichrome A2 enhance RBC membrane stability to a greater extent than do major HbA or hemichrome A. Reductions in ischemic cerebrovascular vascular events are reported in β-thalassemia carriers and HbA2 levels are considerably higher in this population. Episodic declines of cerebral blood flow were shown in bipolar disorder, and we have recently shown a protective role of HbA2 against postpartum episodes in females with bipolar disorder. HbA2’s erythroprotective functions may reduce free Hb and long-term neural injury in MS. PMID:27578976

  17. Therapeutic effect of Colla corii asini on improving anemia and hemoglobin compositions in pregnant women with thalassemia.

    PubMed

    Li, Yanfang; He, Hui; Yang, Lilin; Li, Xiangyi; Li, Daocheng; Luo, Songping

    2016-11-01

    Currently there is no consensus on treating anemia in pregnant thalassemia patients. In China, Colla corii asini (CCA) has been widely used for treating anemia for more than 2000 years. However, its clinical application in the thalassemia population is limited by a lack of quantitative evidence. The present study aims to investigate the therapeutic effect of CCA in increasing hemoglobin (Hb) concentration and improving abnormal hemoglobin compositions in pregnant patients with β-thalassemia. Seventy-two pregnant patients who met inclusion criteria were randomly assigned to either the treatment group or control group. Patients in the treatment group were given 15 g of CCA, while the control group were observed and followed up without any treatment. Levels of Hb, serum iron (SI), serum ferritin (SF) and three types of Hb components [adult hemoglobin (HbA), fetal hemoglobin (HbF), minor adult hemoglobin (HbA2)] were measured before and after treatment. Treatment with CCA led to a significant increase of Hb. The major Hb component induced by CCA was HbA, while levels of both HbA2 and HbF dropped after treatment. CCA treatment significantly increased SI, while SF remained unaffected. Our data suggest that CCA can improve anemia and optimize Hb components in pregnant patients with thalassemia without affecting iron reserves.

  18. A review of variant hemoglobins interfering with hemoglobin A1c measurement.

    PubMed

    Little, Randie R; Roberts, William L

    2009-05-01

    Hemoglobin A1c (HbA1c) is used routinely to monitor long-term glycemic control in people with diabetes mellitus, as HbA1c is related directly to risks for diabetic complications. The accuracy of HbA1c methods can be affected adversely by the presence of hemoglobin (Hb) variants or elevated levels of fetal hemoglobin (HbF). The effect of each variant or elevated HbF must be examined with each specific method. The most common Hb variants worldwide are HbS, HbE, HbC, and HbD. All of these Hb variants have single amino acid substitutions in the Hb beta chain. HbF is the major hemoglobin during intrauterine life; by the end of the first year, HbF falls to values close to adult levels of approximately 1%. However, elevated HbF levels can occur in certain pathologic conditions or with hereditary persistence of fetal hemoglobin. In a series of publications over the past several years, the effects of these four most common Hb variants and elevated HbF have been described. There are clinically significant interferences with some methods for each of these variants. A summary is given showing which methods are affected by the presence of the heterozygous variants S, E, C, and D and elevated HbF. Methods are divided by type (immunoassay, ion-exchange high-performance liquid chromatography, boronate affinity, other) with an indication of whether the result is artificially increased or decreased by the presence of a Hb variant. Laboratorians should be aware of the limitations of their method with respect to these interferences.

  19. Hemoglobin E Hemoglobinopathy in an Adult from Assam with Unusual Presentation: A Diagnostic Dilemma

    PubMed Central

    Kiran, Sunitha S; Aithal, Saraswathy; Belagavi, Charalingappa S

    2016-01-01

    Hemoglobin E (HbE) is estimated to affect at least one million people around the world. Carrier frequency of hemoglobin E/β-thalassemia (HbE/β-thalassemia) is highest in Southeast Asia, reaching as high as 60% in parts of Thailand, Laos, and Cambodia. In the Indian subcontinent, highest frequency is observed in The Northeast regions, but relatively rare in rest of the country. Increasing migration of population from highly affected areas is resulting in rising prevalence in The South and other parts of India. HbE/β-thalassemia is characterized by marked clinical diversity, phenotypic instability, and age-related changes in adaptation to anemia. This paper reports a case of HbE disease in an adult immigrant from Assam and documents the difficulties encountered in the definitive subtyping of HbE hemoglobinopathy. Distinguishing between homozygous HbE disease and HbE/β-thalassemia is a challenge to hematopathologist as both are clinically and hematologically similar. PMID:27365922

  20. Blood Test: Hemoglobin A1C

    MedlinePlus

    ... Your 1- to 2-Year-Old Blood Test: Hemoglobin A1c KidsHealth > For Parents > Blood Test: Hemoglobin A1c A A A What's in this article? ... de sangre: hemoglobina A1c What It Is A hemoglobin A1c (HbA1c) test is used to monitor long- ...

  1. Developing a reference system for the IFCC standardization of HbA2.

    PubMed

    Paleari, Renata; Caruso, Donatella; Kaiser, Patricia; Arsene, Cristian Gabriel; Schaeffer-Reiss, Christine; Van Dorsselaer, Alain; Bissé, Emmanuel; Ospina, Maria; De Jesús, Víctor R; Wild, Barbara; Mosca, Andrea

    2016-05-27

    The importance of hemoglobin A2 (HbA2) as an indicator of the presence of β-thalassemia was established many years ago. However, clinical application of recommended HbA2 cut off values is often hampered due to poor equivalence of HbA2 results among methods and laboratories. Thus, the IFCC standardization program for HbA2 was initiated in 2004 with the goal of achieving a complete reference system for this measurand. HbA2 standardization efforts are still in progress, including the development of a higher-order HbA2 reference measurement procedure and the preparation of a certified reference material in collaboration with the IRMM. Here, we review the past, present and future of HbA2 standardization and describe the current status of HbA2 testing.

  2. Evaluation of 1,5-Anhydroglucitol, Hemoglobin A1c, and Glucose Levels in Youth and Young Adults with Type 1 Diabetes and Healthy Controls

    PubMed Central

    Mehta, Sanjeev N.; Schwartz, Natalie; Wood, Jamie R.; Svoren, Britta M.; Laffel, Lori M.B.

    2013-01-01

    Background and objective Serum 1,5-anhydroglucitol (1,5-AG) is a marker of hyperglycemic excursions in adults with diabetes and HbA1c <8%. We compared 1,5-AG levels among youth and young adults with and without type 1 diabetes (T1D) and investigated the utility of 1,5-AG in the assessment of glycemic status in pediatric T1D. Methods We compared 1,5-AG, HbA1c, and plasma glucose levels in 138 patients with T1D (duration ≥1 year) and 136 healthy controls, ages 10–30 years. Within each group, we investigated associations between 1,5-AG and clinical characteristics, HbA1c and random plasma glucose. For patients with T1D, 1,5-AG was further analyzed according to HbA1c strata: <8%, 8–9%, and >9%. Results Compared to controls, patients with T1D had higher HbA1c (8.5±1.6% vs. 5.1±0.4%, p<0.0001), lower 1,5-AG (4.0±2.0 vs. 24.7±6.4 μg/mL, p<0.0001), and higher glucose (11.1±5.2 vs. 5.1±0.9 mmol/L, p<0.0001). Males had higher 1,5-AG than females within patients (4.5±2.3 vs. 3.4±1.6 μg/mL, p=0.003) and controls (26.0±6.6 vs. 23.5±6.0 μg/mL, p=0.02). 1,5-AG was not correlated with glucose in either group. 1,5-AG was significantly correlated to HbA1c in patients, but not controls. For patients with HbA1c <8%, 1,5-AG demonstrated the widest range and was not predicted by HbA1c; 1,5-AG levels were narrowly distributed among patients with HbA1c ≥8%. Conclusions Youth and young adults with T1D demonstrate similar 1,5-AG levels which are distinct from controls. 1,5-AG assessment may provide unique information beyond that provided by HbA1c in the mid-term assessment of glycemic control in young patients with T1D and HbA1c <8%. PMID:22060802

  3. The Long and Winding Road to Optimal HbA1c Measurement

    PubMed Central

    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

  4. A PEGylated bovine hemoglobin as a potent hemoglobin-based oxygen carrier.

    PubMed

    Wang, Ying; Wang, Linli; Yu, Weili; Gao, Dawei; You, Guoxing; Li, Penglong; Zhang, Shan; Zhang, Jun; Hu, Tao; Zhao, Lian; Zhou, Hong

    2017-01-01

    Hemoglobin (Hb)-based oxygen carriers (HBOCs) have been used as blood substitutes in surgery medicine and oxygen therapeutics for ischemic stroke. As a potent HBOC, the PEGylated Hb has received much attention for its oxygen delivery and plasma expanding ability. Two PEGylated Hbs, Euro-Hb, and MP4 have been developed for clinical trials, using human adult hemoglobin (HbA) as the original substrate. However, HbA was obtained from outdated human blood and its quantity available from this source may not be sufficient for mass production of PEGylated HbA. In contrast, bovine Hb (bHb) has no quantity constraints for its ample resource. Thus, bHb is of potential to function as an alternative substrate to obtain a PEGylated bHb (bHb-PEG). bHb-PEG was prepared under the same reaction condition as HbA-PEG, using maleimide chemistry. The structural, functional, solution and physiological properties of bHb-PEG were determined and compared with those of HbA-PEG. bHb-PEG showed higher hydrodynamic volume, colloidal osmotic pressure, viscosity and P50 than HbA-PEG. The high P50 of bHb can partially compensate the PEGylation-induced perturbation in the R to T state transition of HbA. bHb-PEG was non-vasoactive and could efficiently recover the mean arterial pressure of mice suffering from hemorrhagic shock. Thus, bHb-PEG is expected to function as a potent HBOC for its high oxygen delivery and strong plasma expanding ability. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 33:252-260, 2017.

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

    PubMed Central

    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 < 6.5% were more likely to be older (64 ± 15 versus 60 ± 15 years old, P = 0.01, mean ± STD), female (53.2% versus 38.2%, P = 0.008), leaner (29.7 ± 6.1 versus 33.0 ± 6.6 kg/m2, P = 0.000005), and less likely to be current smokers (18.1% versus 29.1%, P = 0.02) as compared to those with 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

  6. Hemoglobin derivatives

    MedlinePlus

    ... this page: //medlineplus.gov/ency/article/003371.htm Hemoglobin derivatives To use the sharing features on this page, please enable JavaScript. Hemoglobin derivatives are altered forms of hemoglobin . Hemoglobin is ...

  7. Glycosylated Hemoglobin Testing in the National Social Life, Health, and Aging Project

    PubMed Central

    O’Doherty, Katie; Schumm, L. Philip; McClintock, Martha K.; Huang, Elbert S.

    2014-01-01

    Objectives. Longitudinal biomeasures of health are still new in nationally representative social science survey research. Data measuring blood sugar control provide opportunities for understanding the development of diabetes and its complications in older adults, but researchers must be aware that some of the differences across time can be due to variations in measurement procedures. This is a well-recognized issue whenever all samples cannot be assayed at the same time and we sought to present the analytic methods to quantify and adjust for the variation. Method. We collected and analyzed HbA1C, glycated hemoglobin, a biomeasure of average blood sugar concentrations within the past few months. Improvements were made in the collection protocol for Wave 2, and assays were performed by a different lab. Results. The HbA1C data obtained during Wave 1 and Wave 2 are consistent with the expected population distributions for differences by gender, age, race/ethnicity, and diabetes status. Age-adjusted mean HbA1C declined slightly from Wave 1 to Wave 2 by −0.19 (95% confidence interval [CI]: −0.27, −0.10), and the average longitudinal change was −0.12 (95% CI: −0.18, −0.06). Discussion. Collection of HbA1C in Wave 2 permits researchers to examine the relationship between HbA1C and new health and social measures added in Wave 2, and to identify factors related to the change in HbA1C. Changes in collection protocol and labs between waves may have yielded small systematic differences that require analysts to carefully interpret absolute HbA1C values. We recommend analytic methods for cross wave differences in HbA1C and steps to ensure cross wave comparability in future studies PMID:25360021

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

    SciTech Connect

    Nagao, Satoshi; Hirai, Yueki; Kawano, Shin; Imai, Kiyohiro; Suzuki, Akihiro; Yamamoto, Yasuhiko . E-mail: yamamoto@chem.tsukuba.ac.jp

    2007-03-16

    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 {sup 19}F NMR and the O{sub 2} binding properties of the protein have been evaluated through the oxygen equilibrium analysis. The equilibrated orientations of hemes in {alpha}- and {beta}- 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{sub 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{sub 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{sub 2} affinity properties of Hb A. This finding provides new insights into structure-function relationship of Hb A.

  9. Axolotl hemoglobin: cDNA-derived amino acid sequences of two alpha globins and a beta globin from an adult Ambystoma mexicanum.

    PubMed

    Shishikura, Fumio; Takeuchi, Hiro-aki; Nagai, Takatoshi

    2005-11-01

    Erythrocytes of the adult axolotl, Ambystoma mexicanum, have multiple hemoglobins. We separated and purified two kinds of hemoglobin, termed major hemoglobin (Hb M) and minor hemoglobin (Hb m), from a five-year-old male by hydrophobic interaction column chromatography on Alkyl Superose. The hemoglobins have two distinct alpha type globin polypeptides (alphaM and alpham) and a common beta globin polypeptide, all of which were purified in FPLC on a reversed-phase column after S-pyridylethylation. The complete amino acid sequences of the three globin chains were determined separately using nucleotide sequencing with the assistance of protein sequencing. The mature globin molecules were composed of 141 amino acid residues for alphaM globin, 143 for alpham globin and 146 for beta globin. Comparing primary structures of the five kinds of axolotl globins, including two previously established alpha type globins from the same species, with other known globins of amphibians and representatives of other vertebrates, we constructed phylogenetic trees for amphibian hemoglobins and tetrapod hemoglobins. The molecular trees indicated that alphaM, alpham, beta and the previously known alpha major globin were adult types of globins and the other known alpha globin was a larval type. The existence of two to four more globins in the axolotl erythrocyte is predicted.

  10. Hydroxyurea-Increased Fetal Hemoglobin Is Associated with Less Organ Damage and Longer Survival in Adults with Sickle Cell Anemia

    PubMed Central

    Fitzhugh, Courtney D.; Hsieh, Matthew M.; Allen, Darlene; Coles, Wynona A.; Seamon, Cassie; Ring, Michael; Zhao, Xiongce; Minniti, Caterina P.; Rodgers, Griffin P.; Schechter, Alan N.; Tisdale, John F.; Taylor, James G.

    2015-01-01

    Background Adults with sickle cell anemia (HbSS) are inconsistently treated with hydroxyurea. Objectives We retrospectively evaluated the effects of elevating fetal hemoglobin with hydroxyurea on organ damage and survival in patients enrolled in our screening study between 2001 and 2010. Methods An electronic medical record facilitated development of a database for comparison of study parameters based on hydroxyurea exposure and dose. This study is registered with ClinicalTrials.gov, number NCT00011648. Results Three hundred eighty-three adults with homozygous sickle cell disease were analyzed with 59 deaths during study follow-up. Cox regression analysis revealed deceased subjects had more hepatic dysfunction (elevated alkaline phosphatase, Hazard Ratio = 1.005, 95% CI 1.003–1.006, p<0.0.0001), kidney dysfunction (elevated creatinine, Hazard Ratio = 1.13, 95% CI 1.00–1.27, p = 0.043), and cardiopulmonary dysfunction (elevated tricuspid jet velocity on echocardiogram, Hazard Ratio = 2.22, 1.23–4.02, p = 0.0082). Sixty-six percent of subjects were treated with hydroxyurea, although only 66% of those received a dose within the recommended therapeutic range. Hydroxyurea use was associated with improved survival (Hazard Ratio = 0.58, 95% CI 0.34–0.97, p = 0.040). This effect was most pronounced in those taking the recommended dose of 15–35 mg/kg/day (Hazard Ratio 0.36, 95% CI 0.17–0.73, p = 0.0050). Hydroxyurea use was not associated with changes in organ function over time. Further, subjects with higher fetal hemoglobin responses to hydroxyurea were more likely to survive (p = 0.0004). While alkaline phosphatase was lowest in patients with the best fetal hemoglobin response (95.4 versus 123.6, p = 0.0065 and 96.1 versus 113.6U/L, p = 0.041 at first and last visits, respectively), other markers of organ damage were not consistently improved over time in patients with the highest fetal hemoglobin levels. Conclusions Our data suggest that adults should be

  11. Upstream promoter mutation associated with a modest elevation of fetal hemoglobin expression in human adults.

    PubMed

    Gilman, J G; Mishima, N; Wen, X J; Kutlar, F; Huisman, T H

    1988-07-01

    In hereditary persistence of fetal hemoglobin, Hb F (alpha 2 gamma 2) is elevated after birth. Screening of sickle cell patients has revealed a family with elevated Hb F and high A gamma values. The propositus was a sickle cell patient with approximately 25% Hb F and 68.4% A gamma. He was heterozygous for the Benin (#19) and Mor beta S haplotypes. Five AS relatives with the Mor haplotype had 2.5% +/- 0.9% fetal hemoglobin and 92.8% +/- 2.8% A gamma, whereas two with the Benin haplotype had normal fetal hemoglobin (0.5%). The Mor haplotype is thus associated with the elevated Hb F in this family. The 13-kilobase (kb) Bg/II fragment containing the G gamma and A gamma genes of the Mor haplotype was cloned, and the G gamma and A gamma promoters sequenced from -383 to beyond the Cap sites. The Mor G gamma gene was normal, but the A gamma gene had a unique C----T mutation at -202. A different mutation at -202 of G gamma (C----G) was previously detected by other researchers in association with considerably higher Hb F in AS cases (15% to 25%). These data suggest either that -202 mutations affect the G gamma and A gamma promoters differently or that different nucleotide substitutions at -202 have divergent effects. Alternatively, additional unknown mutations could cause the differences in gene expression.

  12. Protonation states of histidine and other key residues in deoxy normal human adult hemoglobin by neutron protein crystallography

    SciTech Connect

    Kovalevsky, Andrey; Chatake, Toshiyuki; Shibayama, Naoya; Park, Sam-Yong; Ishikawa, Takuya; Mustyakimov, Marat; Fisher, S. Zoe; Langan, Paul; Morimoto, Yukio

    2010-11-01

    Using neutron diffraction analysis, the protonation states of 35 of 38 histidine residues were determined for the deoxy form of normal human adult hemoglobin. Distal and buried histidines may contribute to the increased affinity of the deoxy state for hydrogen ions and its decreased affinity for oxygen compared with the oxygenated form. The protonation states of the histidine residues key to the function of deoxy (T-state) human hemoglobin have been investigated using neutron protein crystallography. These residues can reversibly bind protons, thereby regulating the oxygen affinity of hemoglobin. By examining the OMIT F{sub o} − F{sub c} and 2F{sub o} − F{sub c} neutron scattering maps, the protonation states of 35 of the 38 His residues were directly determined. The remaining three residues were found to be disordered. Surprisingly, seven pairs of His residues from equivalent α or β chains, αHis20, αHis50, αHis58, αHis89, βHis63, βHis143 and βHis146, have different protonation states. The protonation of distal His residues in the α{sub 1}β{sub 1} heterodimer and the protonation of αHis103 in both subunits demonstrates that these residues may participate in buffering hydrogen ions and may influence the oxygen binding. The observed protonation states of His residues are compared with their ΔpK{sub a} between the deoxy and oxy states. Examination of inter-subunit interfaces provided evidence for interactions that are essential for the stability of the deoxy tertiary structure.

  13. Absolute measurement of cerebral optical coefficients, hemoglobin concentration and oxygen saturation in old and young adults with near-infrared spectroscopy

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We present near-infrared spectroscopy measurement of absolute cerebral hemoglobin concentration and saturation in a large sample of 36 healthy elderly (mean age, 85 ± 6 years) and 19 young adults (mean age, 28 ± 4 years). Non-invasive measurements were obtained on the forehead using a commercially a...

  14. Cutoff Point of HbA1c for Diagnosis of Diabetes Mellitus in Chinese Individuals

    PubMed Central

    Liu, Ming-Chuan; Li, Xin-Yu; Liu, Xu-Han; Feng, Qiu-Xia; Lu, Lu; Zhu, Zhu; Liu, Ying-Shu; Zhao, Wei; Gao, Zheng-Nan

    2016-01-01

    Background The purpose of the present study was to find the optimal threshold of glycated hemoglobin (HbA1c) for diagnosis of diabetes mellitus in Chinese individuals. Methods A total of 8 391 subjects (including 2 133 men and 6 258 women) aged 40–90 years with gradable retinal photographs were recruited. The relationship between HbA1c and diabetic retinopathy (DR) was examined. Receiver operating characteristic (ROC) curves were used to find the optimal threshold of HbA1c in screening DR and diagnosing diabetes. Results HbA1c values in patients with DR were significantly higher than in those with no DR. The ROC curve for HbA1c had an area under the curve of 0.881 (95%CI 0.857–0.905; P = 0.000). HbA1c at a cutoff of 6.5% had a high sensitivity (80.6%) and specificity (86.9%) for detecting DR. Conclusions HbA1c can be used to diagnose diabetes in a Chinese population, and the optimal HbA1c cutoff point for diagnosis is 6.5%. PMID:27861599

  15. Glycated Hemoglobin Level and Mortality in a Nondiabetic Population with CKD

    PubMed Central

    Metzger, Marie; Haymann, Jean-Philippe; Boffa, Jean-Jacques; Flamant, Martin; Vrtovsnik, François; Houillier, Pascal; Stengel, Benedicte; Thervet, Eric

    2015-01-01

    Background and objectives Glycated hemoglobin (HbA1c) is used to diagnose diabetes mellitus (DM) and guide its management. The association between higher HbA1c and progression to ESRD and mortality has been demonstrated in populations with DM. This study examined the association between HbA1c and these end points in a population with CKD and without DM. Design, setting, participants, & measurements In the hospital-based NephroTest cohort study, measured GFR (mGFR) was taken by 51Cr-EDTA renal clearance and HbA1c in 1165 adults with nondialysis CKD stages 1–5 and without DM between January 2000 and December 2010. The median follow-up was 3.48 years (interquartile range, 1.94–5.82) for the competing events of ESRD and pre-ESRD mortality. Time-fixed and time-dependent Cox models were used to estimate hazard ratios (HRs) for ESRD and mortality according to HbA1c, treated continuously or in tertiles. Results At inclusion, the mean mGFR was 42.2±19.9 ml/min per 1.73 m2, and the mean HbA1c value was 5.5%±0.5%. During follow-up, 109 patients died, and 162 patients reached ESRD. Pre-ESRD mortality was significantly associated with HbA1c treated continuously: for every 1% higher HbA1c, the crude HR was 2.16 (95% confidence interval [95% CI], 1.27 to 3.68), and it was 1.85 (95% CI, 1.05 to 3.24) after adjustment for mGFR and other risk factors of death. After excluding incident diabetes over time, the updated mean of HbA1c remained significantly associated with higher mortality risk: adjusted HR for the highest (5.7%–6.4%) versus the lowest tertile (<5.3%) was 2.62 (95% CI, 1.16 to 5.91). There was no association with ESRD risk after adjustment for risk factors of CKD progression. Conclusions In a CKD cohort, HbA1c values in the prediabetes range are associated with mortality. Such values should be therefore included among the risk factors for negative outcomes in CKD populations. PMID:25979978

  16. Hemoglobin (image)

    MedlinePlus

    Hemoglobin is the most important component of red blood cells. It is composed of a protein called ... exchanged for carbon dioxide. Abnormalities of an individual's hemoglobin value can indicate defects in the normal balance ...

  17. Electrochemical detection of HbA1c, a marker [correction of maker] for diabetes, using a flow immunoassay system.

    PubMed

    Tanaka, Tsuyoshi; Tsukube, Shoko; Izawa, Kojiro; Okochi, Mina; Lim, Tae-Kyu; Watanabe, Shugo; Harada, Manabu; Matsunaga, Tadashi

    2007-04-15

    An on-chip electrochemical flow immunoassay system for the detection of hemoglobin A1c (HbA1c) was developed using anti-human hemoglobin (Hb) IgG labeled with ferrocene monocarboxylic acid (Fc-COOH) and boronate-affinity chromatography. An on-chip column packed with boronate-activated agarose beads was used for the separation of HbA1c from both non-glycated Hb and free antibody. Anti-human Hb IgG conjugated to Fc-COOH (Fc-IgG) was used for the electrochemical detection of HbA1c. The assay procedure included immunoreactions with Fc-IgG and HbA1c, separation of immunocomplexes by boronate affinity, and electrochemical detection of Fc-IgG-HbA1c immunocomplexes. The immunoreaction mixtures were injected onto a boronate-affinity column. HbA1c-antibody complexes were then trapped onto the column by the affinity of HbA1c to boronic acid. Subsequently, elution buffer containing sorbitol was applied to elute HbA1c-antibody complexes and a current was detected by applying 600 mV versus Ag/AgCl. The elution signal was an estimation of the HbA1c amount. A linear correlation between the increase of current and HbA1c concentration was obtained up to an HbA1c concentration of 500 microg/ml. The HbA1c flow immunoassay was successfully achieved using hemolysates. This electrochemical flow immunoassay system enabled us to construct a novel point-of-care testing device for the monitoring of glycated proteins including HbA1c.

  18. Use of liposome encapsulated hemoglobin as an oxygen carrier for fetal and adult rat liver cell culture.

    PubMed

    Montagne, Kevin; Huang, Hongyun; Ohara, Keikou; Matsumoto, Kunio; Mizuno, Atsushi; Ohta, Katsuji; Sakai, Yasuyuki

    2011-11-01

    Engineering liver tissue constructs with sufficient cell mass for transplantation implies culturing large numbers of hepatocytes in a reduced volume; however, providing sufficient oxygen to dense cell cultures is still not feasible using only conventional culture medium. Liposome-encapsulated hemoglobin (LEH), an oxygen-carrying blood substitute originally designed for short-term perfusion, may be a good candidate as an oxygen carrier to cultured liver cells. In this study, we investigated the feasibility of maintaining long term hepatocyte cultures using LEH. Primary fetal and adult rat liver cells were directly exposed to LEH for 6 to 14 days in static culture or in a perfused flat plate bioreactor. The functions and viability of adult rat hepatocytes exposed to LEH were not adversely affected in static monolayer culture and were even improved in the bioreactor. However, some cytotoxicity of LEH was observed with fetal rat liver cells after 4 days of culture. LEH, though a suitable oxygen carrier for long-term culture of mature hepatocytes, is not suitable in its present form for perfusing fetal hepatocyte cultures in direct contact with the liposomes; either the LEH will have to be made less toxic or a more sophisticated bioreactor that prevents the direct contact between hepatocytes and perfusates will have to be designed if fetal cells are to be used for liver tissue engineering.

  19. Effects of thyroid status on glycated hemoglobin

    PubMed Central

    Bhattacharjee, Rana; Thukral, Anubhav; Chakraborty, Partha Pratim; Roy, Ajitesh; Goswami, Soumik; Ghosh, Sujoy; Mukhopadhyay, Pradip; Mukhopadhyay, Satinath; Chowdhury, Subhankar

    2017-01-01

    Introduction: Glycated hemoglobin (HbA1c) can be altered in different conditions. We hypothesize that HbA1c levels may change due to altered thyroid status, possibly due to changes in red blood cell (RBC) turnover. Objectives: The objective of this study was to determine the effects of altered thyroid status on HbA1c levels in individuals without diabetes, with overt hyper- and hypo-thyroidism, and if present, whether such changes in HbA1c are reversed after achieving euthyroid state. Methods: Euglycemic individuals with overt hypo- or hyper-thyroidism were selected. Age- and sex-matched controls were recruited. Baseline HbA1c and reticulocyte counts (for estimation of RBC turnover) were estimated in all the patients and compared. Thereafter, stable euthyroidism was achieved in a randomly selected subgroup and HbA1c and reticulocyte count was reassessed. HbA1c values and reticulocyte counts were compared with baseline in both the groups. Results: Hb A1c in patients initially selected was found to be significantly higher in hypothyroid group. HbA1c values in hyperthyroid patients were not significantly different from controls. HbA1c reduction and rise in reticulocyte count were significant in hypothyroid group following treatment without significant change in glucose level. Hb A1c did not change significantly following treatment in hyperthyroid group. The reticulocyte count, however, decreased significantly. Conclusion: Baseline HbA1c levels were found to be significantly higher in hypothyroid patients, which reduced significantly after achievement of euthyroidism without any change in glucose levels. Significant baseline or posttreatment change was not observed in hyperthyroid patients. Our study suggests that we should be cautious while interpreting HbA1c data in patients with hypothyroidism. PMID:28217494

  20. Reactivating Fetal Hemoglobin Expression in Human Adult Erythroblasts Through BCL11A Knockdown Using Targeted Endonucleases

    PubMed Central

    Bjurström, Carmen F; Mojadidi, Michelle; Phillips, John; Kuo, Caroline; Lai, Stephen; Lill, Georgia R; Cooper, Aaron; Kaufman, Michael; Urbinati, Fabrizia; Wang, Xiaoyan; Hollis, Roger P; Kohn, Donald B

    2016-01-01

    We examined the efficiency, specificity, and mutational signatures of zinc finger nucleases (ZFNs), transcriptional activator-like effector nucleases (TALENs), and clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9 systems designed to target the gene encoding the transcriptional repressor BCL11A, in human K562 cells and human CD34+ progenitor cells. ZFNs and TALENs were delivered as in vitro transcribed mRNA through electroporation; CRISPR/Cas9 was codelivered by Cas9 mRNA with plasmid-encoded guideRNA (gRNA) (pU6.g1) or in vitro transcribed gRNA (gR.1). Analyses of efficacy revealed that for these specific reagents and the delivery methods used, the ZFNs gave rise to more allelic disruption in the targeted locus compared to the TALENs and CRISPR/Cas9, which was associated with increased levels of fetal hemoglobin in erythroid cells produced in vitro from nuclease-treated CD34+ cells. Genome-wide analysis to evaluate the specificity of the nucleases revealed high specificity of this specific ZFN to the target site, while specific TALENs and CRISPRs evaluated showed off-target cleavage activity. ZFN gene-edited CD34+ cells had the capacity to engraft in NOD-PrkdcSCID-IL2Rγnull mice, while retaining multi-lineage potential, in contrast to TALEN gene-edited CD34+ cells. CRISPR engraftment levels mirrored the increased relative plasmid-mediated toxicity of pU6.g1/Cas9 in hematopoietic stem/progenitor cells (HSPCs), highlighting the value for the further improvements of CRISPR/Cas9 delivery in primary human HSPCs. PMID:28131278

  1. Monosodium glutamate intake increases hemoglobin level over 5 years among Chinese adults.

    PubMed

    Shi, Zumin; Yuan, Baojun; Taylor, Anne W; Dal Grande, Eleonora; Wittert, Gary A

    2012-09-01

    The aim of this analysis was to determine the relationship between monosodium glutamate (MSG) intake and change in hemoglobin (Hb) levels and the risk of anemia over 5 years in 1197 Chinese men and women who participated in the Jiangsu Nutrition Study (JIN). MSG intake and Hb were quantitatively assessed in 2002 and followed up in 2007. Diet and lifestyle factors were assessed at both time points. There was a positive association between MSG intake and increase in Hb among men but not women. In the multivariate model adjusting for demographic and lifestyle factors as well as baseline dietary pattern, the beta values and 95% confidence interval for Hb changes across quartiles of MSG intake were 0, 0.67(0.04-1.29), 0.99(0.38-1.60), 0.73(0.13-1.34) among men (p for trend 0.091); 0, -0.01(-0.45-0.43), 0.23(-0.25-0.71), and -0.45(-0.96-0.05) among women (p for trend 0.087). Among anemic participants at baseline, there was a significant inverse association between MSG intake and the risk of anemia at follow-up. Comparing extreme quartiles of MSG intake among those anemic at baseline, the relative risk for persistent anemia at follow-up was 0.49 (95% CI: 0.28-0.86, p < 0.01). The association was independent of dietary patterns and lifestyle factors. A dose-response relationship between MSG intake and increase in Hb levels among anemic participants was seen. MSG intake may have independent Hb-increasing effects, especially among men and those anemic at baseline.

  2. Application of glycated hemoglobin in the perinatal period

    PubMed Central

    Yu, Haiyan; Qi, Xiaorong; Wang, Xiaodong

    2014-01-01

    Glycated hemoglobin (HbA1c) is a special fragment formed by the binding of glucose to the C chain or D chain of hemoglobin A and as a result of non-enzymatic catalysis of mature hemoglobin and glucose, which is an indicator used to evaluate the blood glucose control in diabetes mellitus (DM) patients. Recent researches indicated that HbA1c could be applied in gestational diabetes mellitus (GDM) and pregnancy combined DM, and increasing of HbA1c was close associated with adverse outcomes of women with pregnancy combined DM and GDM. HbA1c was reported to have a significant importance in monitoring congenital malformation, abortion, perinatal mortality, preeclampsia, postpartum abnormal glucose metabolism, vascular complications and so on, which could be a test item during the second trimester. Sensitivity of HbA1c in diagnoses of DM is lower than oral glucose tolerance test (OGTT), thus OGTT is still the golden standard of GDM. Emphasis should be put on standardization of detection and threshold of HbA1c and establishment of HbA1c normal ranges of different trimesters, when HbA1c is used to diagnose pregnancy combined DM and GDM, and evaluate effects of treatments. PMID:25663962

  3. A Comparison of hs-CRP Levels in New Diabetes Groups Diagnosed Based on FPG, 2-hPG, or HbA1c Criteria.

    PubMed

    Tutuncu, Yildiz; Satman, Ilhan; Celik, Selda; Dinccag, Nevin; Karsidag, Kubilay; Telci, Aysegul; Genc, Sema; Issever, Halim; Tuomilehto, Jaakko; Omer, Beyhan

    2016-01-01

    Fasting plasma glucose (FPG) and hemoglobin A1c (HbA1c) have been used to diagnose new-onset diabetes mellitus (DM) in order to simplify the diagnostic tests compared with the 2-hour oral glucose tolerance test (OGTT; 2-hPG). We aimed to identify optimal cut-off points of high sensitive C-reactive protein (hs-CRP) in new-onset DM people based on FPG, 2-hPG, or HbA1c methods. Data derived from recent population-based survey in Turkey (TURDEP-II). The study included 26,499 adult people (63% women, response rate 85%). The mean serum concentration of hs-CRP in women was higher than in men (p < 0.001). The people with new-onset DM based on HbA1c had higher mean hs-CRP level than FPG based and 2-hPG based DM cases. In HbA1c, 2-hPG, and FPG based new-onset DM people, cut-off levels of hs-CRP in women were 2.9, 2.1, and 2.5 mg/L [27.5, 19.7, and 23.5 nmol/L] and corresponding values in men were 2.0, 1.8, and 1.8 mg/L (19.0, 16.9, and 16.9 nmol/L), respectively (sensitivity 60-65% and specificity 54-64%). Our results revealed that hs-CRP may not further strengthen the diagnosis of new-onset DM. Nevertheless, the highest hs-CRP level observed in new-onset DM people diagnosed with HbA1c criterion supports the general assumption that this method might recognize people in more advanced diabetic stage compared with other diagnostic methods.

  4. Effects of Hemoglobin Variants on Hemoglobin A1c Values Measured Using a High-Performance Liquid Chromatography Method

    PubMed Central

    De-La-Iglesia, Silvia; Ropero, Paloma; Nogueira-Salgueiro, Patricia; Santana-Benitez, Jesus

    2014-01-01

    Hemoglobin A1c (HbA1c) is routinely used to monitor long-term glycemic control and for diagnosing diabetes mellitus. However, hemoglobin (Hb) gene variants/modifications can affect the accuracy of some methods. The potential effect of Hb variants on HbA1c measurements was investigated using a high-performance liquid chromatography (HPLC) method compared with an immunoturbimetric assay. Fasting plasma glucose (FPG) and HbA1c levels were measured in 42 371 blood samples. Samples producing abnormal chromatograms were further analyzed to characterize any Hb variants. Fructosamine levels were determined in place of HbA1c levels when unstable Hb variants were identified. Abnormal HPLC chromatograms were obtained for 160 of 42 371 samples. In 26 samples HbS was identified and HbA1c results correlated with FPG. In the remaining 134 samples HbD, Hb Louisville, Hb Las Palmas, Hb N-Baltimore, or Hb Porto Alegre were identified and HbA1c did not correlate with FPG. These samples were retested using an immunoturbidimetric assay and the majority of results were accurate; only 3 (with the unstable Hb Louisville trait) gave aberrant HbA1c results. Hb variants can affect determination of HbA1c levels with some methods. Laboratories should be aware of Hb variants occurring locally and choose an appropriate HbA1c testing method. PMID:25355712

  5. What is the Role of HbA1c in Diabetic Hemodialysis Patients?

    PubMed

    Coelho, Silvia

    2016-01-01

    The definition of a good glycemic control in patients with diabetes mellitus on hemodialysis is far from settled. In the general population, hemoglobin A1c is highly correlated with the average glycemia of the last 8-12 weeks. However, in hemodialysis patients, the correlation of hbA1c with glycemia is weaker as it also reflects changes in hemoglobin characteristics and red blood cells half-life. As expected, studies show that the association between HbA1c and outcomes in these patients differ from the general population. Therefore, the value of HbA1c in the treatment of hemodialysis patients has been questioned. Guidelines are generally cautious in their recommendations about possible targets of HbA1c in this population. Indeed, the risk of not treating hyperglycemia should be weighed against the particularly high risk of precipitating hypoglycemia in dialysis patients. In this review, a critical analysis of the current role of HbA1c in the care of hemodialysis patients is presented.

  6. Significance of HbA1c Test in Diagnosis and Prognosis of Diabetic Patients

    PubMed Central

    Sherwani, Shariq I.; Khan, Haseeb A.; Ekhzaimy, Aishah; Masood, Afshan; Sakharkar, Meena K.

    2016-01-01

    Diabetes is a global endemic with rapidly increasing prevalence in both developing and developed countries. The American Diabetes Association has recommended glycated hemoglobin (HbA1c) as a possible substitute to fasting blood glucose for diagnosis of diabetes. HbA1c is an important indicator of long-term glycemic control with the ability to reflect the cumulative glycemic history of the preceding two to three months. HbA1c not only provides a reliable measure of chronic hyperglycemia but also correlates well with the risk of long-term diabetes complications. Elevated HbA1c has also been regarded as an independent risk factor for coronary heart disease and stroke in subjects with or without diabetes. The valuable information provided by a single HbA1c test has rendered it as a reliable biomarker for the diagnosis and prognosis of diabetes. This review highlights the role of HbA1c in diagnosis and prognosis of diabetes patients. PMID:27398023

  7. Absolute measurement of cerebral optical coefficients, hemoglobin concentration and oxygen saturation in old and young adults with near-infrared spectroscopy.

    PubMed

    Hallacoglu, Bertan; Sassaroli, Angelo; Wysocki, Michael; Guerrero-Berroa, Elizabeth; Schnaider Beeri, Michal; Haroutunian, Vahram; Shaul, Merav; Rosenberg, Irwin H; Troen, Aron M; Fantini, Sergio

    2012-08-01

    We present near-infrared spectroscopy measurement of absolute cerebral hemoglobin concentration and saturation in a large sample of 36 healthy elderly (mean age, 85 ± 6 years) and 19 young adults (mean age, 28 ± 4 years). Non-invasive measurements were obtained on the forehead using a commercially available multi-distance frequency-domain system and analyzed using a diffusion theory model for a semi-infinite, homogeneous medium with semi-infinite boundary conditions. Our study included repeat measurements, taken five months apart, on 16 elderly volunteers that demonstrate intra-subject reproducibility of the absolute measurements with cross-correlation coefficients of 0.9 for absorption coefficient (μa), oxy-hemoglobin concentration ([HbO2]), and total hemoglobin concentration ([HbT]), 0.7 for deoxy-hemoglobin concentration ([Hb]), 0.8 for hemoglobin oxygen saturation (StO2), and 0.7 for reduced scattering coefficient (μ's). We found significant differences between the two age groups. Compared to young subjects, elderly subjects had lower cerebral [HbO2], [Hb], [HbT], and StO2 by 10 ± 4 μM, 4 ± 3 μM, 14 ± 5 μM, and 6%±5%, respectively. Our results demonstrate the reliability and robustness of multi-distance near-infrared spectroscopy measurements based on a homogeneous model in the human forehead on a large sample of human subjects. Absolute, non-invasive optical measurements on the brain, such as those presented here, can significantly advance the development of NIRS technology as a tool for monitoring resting/basal cerebral perfusion, hemodynamics, oxygenation, and metabolism.

  8. Dietary glycemic index and glycemic load in relation to HbA1c in Japanese obese adults: a cross-sectional analysis of the Saku Control Obesity Program

    PubMed Central

    2012-01-01

    Background Dietary glycemic index or load is thought to play an important role in glucose metabolism. However, few studies have investigated the relation between glycemic index (GI) or load (GL) and glycemia in Asian populations. In this cross-sectional analysis of a randomized controlled trial, the Saku Control Obesity Program, we examined the relation between the baseline GI or GL and glycemia (HbA1c and fasting plasma glucose [FPG] levels), insulin resistance (HOMA-IR), β-cell function (HOMA-β), and other metabolic risk factors (lipid levels, diastolic and systolic blood pressure, and adiposity measures). Methods The participants were 227 obese Japanese women and men. We used multiple linear regression models and logistic regression models to adjust for potential confounding factors such as age, sex, visceral fat area, total energy intake, and physical activity levels. Results After adjustments for potential confounding factors, GI was not associated with HbA1c, but GL was positively associated with HbA1c. For increasing quartiles of GI, the adjusted mean HbA1c were 6.3%, 6.7%, 6.4%, and 6.4% (P for trend = 0.991). For increasing quartiles of GL, the adjusted mean HbA1c were 6.2%, 6.2%, 6.6%, and 6.5% (P for trend = 0.044). In addition, among participants with HbA1c ≥ 7.0%, 20 out of 28 (71%) had a high GL (≥ median); the adjusted odds ratio for HbA1c ≥ 7.0% among participants with higher GL was 3.1 (95% confidence interval [CI] = 1.2 to 8.1) compared to the participants with a lower GL (

  9. Common Variants at 10 Genomic Loci Influence Hemoglobin A1C Levels via Glycemic and Nonglycemic Pathways

    PubMed Central

    Soranzo, Nicole; Sanna, Serena; Wheeler, Eleanor; Gieger, Christian; Radke, Dörte; Dupuis, Josée; Bouatia-Naji, Nabila; Langenberg, Claudia; Prokopenko, Inga; Stolerman, Elliot; Sandhu, Manjinder S.; Heeney, Matthew M.; Devaney, Joseph M.; Reilly, Muredach P.; Ricketts, Sally L.

    2010-01-01

    OBJECTIVE Glycated hemoglobin (HbA1c), used to monitor and diagnose diabetes, is influenced by average glycemia over a 2- to 3-month period. Genetic factors affecting expression, turnover, and abnormal glycation of hemoglobin could also be associated with increased levels of HbA1c. We aimed to identify such genetic factors and investigate the extent to which they influence diabetes classification based on HbA1c levels. RESEARCH DESIGN AND METHODS We studied associations with HbA1c in up to 46,368 nondiabetic adults of European descent from 23 genome-wide association studies (GWAS) and 8 cohorts with de novo genotyped single nucleotide polymorphisms (SNPs). We combined studies using inverse-variance meta-analysis and tested mediation by glycemia using conditional analyses. We estimated the global effect of HbA1c loci using a multilocus risk score, and used net reclassification to estimate genetic effects on diabetes screening. RESULTS Ten loci reached genome-wide significant association with HbA1c, including six new loci near FN3K (lead SNP/P value, rs1046896/P = 1.6 × 10−26), HFE (rs1800562/P = 2.6 × 10−20), TMPRSS6 (rs855791/P = 2.7 × 10−14), ANK1 (rs4737009/P = 6.1 × 10−12), SPTA1 (rs2779116/P = 2.8 × 10−9) and ATP11A/TUBGCP3 (rs7998202/P = 5.2 × 10−9), and four known HbA1c loci: HK1 (rs16926246/P = 3.1 × 10−54), MTNR1B (rs1387153/P = 4.0 × 10−11), GCK (rs1799884/P = 1.5 × 10−20) and G6PC2/ABCB11 (rs552976/P = 8.2 × 10−18). We show that associations with HbA1c are partly a function of hyperglycemia associated with 3 of the 10 loci (GCK, G6PC2 and MTNR1B). The seven nonglycemic loci accounted for a 0.19 (% HbA1c) difference between the extreme 10% tails of the risk score, and would reclassify ∼2% of a general white population screened for diabetes with HbA1c. CONCLUSIONS GWAS identified 10 genetic loci reproducibly associated with HbA1c. Six are novel and seven map to loci where rarer variants cause hereditary anemias and iron

  10. Hemoglobin electrophoresis

    MedlinePlus

    ... is an abnormal form of hemoglobin associated with sickle cell anemia . In people with this condition, the red blood ... symptoms are much milder than they are in sickle cell anemia. Other, less common, abnormal Hb molecules cause other ...

  11. Gene duplication and the evolution of hemoglobin isoform differentiation in birds.

    PubMed

    Grispo, Michael T; Natarajan, Chandrasekhar; Projecto-Garcia, Joana; Moriyama, Hideaki; Weber, Roy E; Storz, Jay F

    2012-11-02

    The majority of bird species co-express two functionally distinct hemoglobin (Hb) isoforms in definitive erythrocytes as follows: HbA (the major adult Hb isoform, with α-chain subunits encoded by the α(A)-globin gene) and HbD (the minor adult Hb isoform, with α-chain subunits encoded by the α(D)-globin gene). The α(D)-globin gene originated via tandem duplication of an embryonic α-like globin gene in the stem lineage of tetrapod vertebrates, which suggests the possibility that functional differentiation between the HbA and HbD isoforms may be attributable to a retained ancestral character state in HbD that harkens back to a primordial, embryonic function. To investigate this possibility, we conducted a combined analysis of protein biochemistry and sequence evolution to characterize the structural and functional basis of Hb isoform differentiation in birds. Functional experiments involving purified HbA and HbD isoforms from 11 different bird species revealed that HbD is characterized by a consistently higher O(2) affinity in the presence of allosteric effectors such as organic phosphates and Cl(-) ions. In the case of both HbA and HbD, analyses of oxygenation properties under the two-state Monod-Wyman-Changeux allosteric model revealed that the pH dependence of Hb-O(2) affinity stems primarily from changes in the O(2) association constant of deoxy (T-state)-Hb. Ancestral sequence reconstructions revealed that the amino acid substitutions that distinguish the adult-expressed Hb isoforms are not attributable to the retention of an ancestral (pre-duplication) character state in the α(D)-globin gene that is shared with the embryonic α-like globin gene.

  12. Gene Duplication and the Evolution of Hemoglobin Isoform Differentiation in Birds*

    PubMed Central

    Grispo, Michael T.; Natarajan, Chandrasekhar; Projecto-Garcia, Joana; Moriyama, Hideaki; Weber, Roy E.; Storz, Jay F.

    2012-01-01

    The majority of bird species co-express two functionally distinct hemoglobin (Hb) isoforms in definitive erythrocytes as follows: HbA (the major adult Hb isoform, with α-chain subunits encoded by the αA-globin gene) and HbD (the minor adult Hb isoform, with α-chain subunits encoded by the αD-globin gene). The αD-globin gene originated via tandem duplication of an embryonic α-like globin gene in the stem lineage of tetrapod vertebrates, which suggests the possibility that functional differentiation between the HbA and HbD isoforms may be attributable to a retained ancestral character state in HbD that harkens back to a primordial, embryonic function. To investigate this possibility, we conducted a combined analysis of protein biochemistry and sequence evolution to characterize the structural and functional basis of Hb isoform differentiation in birds. Functional experiments involving purified HbA and HbD isoforms from 11 different bird species revealed that HbD is characterized by a consistently higher O2 affinity in the presence of allosteric effectors such as organic phosphates and Cl− ions. In the case of both HbA and HbD, analyses of oxygenation properties under the two-state Monod-Wyman-Changeux allosteric model revealed that the pH dependence of Hb-O2 affinity stems primarily from changes in the O2 association constant of deoxy (T-state)-Hb. Ancestral sequence reconstructions revealed that the amino acid substitutions that distinguish the adult-expressed Hb isoforms are not attributable to the retention of an ancestral (pre-duplication) character state in the αD-globin gene that is shared with the embryonic α-like globin gene. PMID:22962007

  13. Are the ADA hemoglobin A(1c) criteria relevant for the diagnosis of type 2 diabetes in youth?

    PubMed

    Kapadia, Chirag R

    2013-02-01

    Diagnostic criteria for diabetes in children have not been established with nearly the rigor as that employed in adults. Recently revised American Diabetes Association (ADA) criteria allowed utilization of hemoglobin A(1c) (HbA1c) ≥ 6.5 % for diagnosis of diabetes. A recent series of pediatric studies appear to show that HbA1c has lower sensitivity than Fasting plasma glucose (FPG) or oral glucose tolerance test (OGTT). However, FPG and OGTT have themselves never been validated in children. Studies to validate diagnostic thresholds in children appear unlikely to take place. Thus, accepting the major ADA diagnostic criteria appears to be the best course of action for the pediatric community. One area in which correlation studies between HbA1c and FPG or OGTT might shed light is in the definition of criteria for intervention in 'pre-diabetes,' as the Diabetes Prevention Program Trial did not use HbA1c. However, such treatment, and the exact diagnostic thresholds at which it should be initiated in children, remains unproven.

  14. Body fat percentage and hemoglobin levels are related to blood lead, cadmium, and mercury concentrations in a Korean Adult Population (KNHANES 2008-2010).

    PubMed

    Park, Sunmin; Lee, Byung-Kook

    2013-03-01

    Body stores of lead, cadmium, and mercury are determined by the levels in the circulation, and their levels in blood may be related to hemoglobin levels and their absorption by soft tissue and bone. We investigated the association of body fat percentage, hemoglobin levels, and nutrient intakes with the blood concentrations of lead, cadmium, and mercury in a Korean adult population. This study was based on data from the 2008-2010 Korean National Health and Nutritional Examination Survey (n = 4,522, aged ≥ 20 years), which examined nutritional, biochemical, and health-related parameters. A multiple regression analysis after controlling for covariates of age, body mass index, residence area, education level, smoking and drinking status, and bone mineral density for men, with menopausal status added for women in addition to covariates for men indicated that blood lead and mercury levels were negatively associated with body fat percentage only in men, and blood lead, cadmium, and mercury levels were positively related to hemoglobin levels in both genders. Additionally, blood lead levels were negatively associated with fat and carbohydrate intake in both men and women but blood mercury levels were only in men, but not women. Sodium intake was a positive predictor of blood lead levels in both genders but was a positive predictor of blood cadmium levels only in men. In conclusion, body fat percentage and hemoglobin levels need to be recognized as confounding factors when considering blood levels of lead, cadmium and mercury as biomarkers for their exposure. Fat, carbohydrates and sodium intakes are also associated with heavy metal levels in the circulation.

  15. Selection of aptamers specific for glycated hemoglobin and total hemoglobin using on-chip SELEX.

    PubMed

    Lin, Hsin-I; Wu, Ching-Chu; Yang, Ching-Hsuan; Chang, Ko-Wei; Lee, Gwo-Bin; Shiesh, Shu-Chu

    2015-01-21

    Blood glycated hemoglobin (HbA1c) levels reflecting average glucose concentrations over the past three months are fundamental for the diagnosis, monitoring, and risk assessment of diabetes. It has been hypothesized that aptamers, which are single-stranded DNAs or RNAs that demonstrate high affinity to a large variety of molecules ranging from small drugs, metabolites, or proteins, could be used for the measurement of HbA1c. Aptamers are selected through an in vitro process called systematic evolution of ligands by exponential enrichment (SELEX), and they can be chemically synthesized with high reproducibility at relatively low costs. This study therefore aimed to select HbA1c- and hemoglobin (Hb)-specific single-stranded DNA aptamers using an on-chip SELEX protocol. A microfluidic SELEX chip was developed to continuously and automatically carry out multiple rounds of SELEX to screen specific aptamers for HbA1c and Hb. HbA1c and Hb were first coated onto magnetic beads. Following several rounds of selection and enrichment with a randomized 40-mer DNA library, specific oligonucleotides were selected. The binding specificity and affinity were assessed by competitive and binding assays. Using the developed microfluidic system, the incubation and partitioning times were greatly decreased, and the entire process was shortened dramatically. Both HbA1c- and Hb-specific aptamers selected by the microfluidic system showed high specificity and affinity (dissociation constant, Kd = 7.6 ± 3.0 nM and 7.3 ± 2.2 nM for HbA1c and Hb, respectively). With further refinements in the assay, these aptamers may replace the conventional antibodies for in vitro diagnostics applications in the near future.

  16. A hemoglobin A1C immunoassay method not affected by carbamylated hemoglobin.

    PubMed

    Rose, A M; Tongate, C; Valdes, R

    1995-01-01

    Hemoglobin A1C (HbA1C) methods based on charge separation of Hb species are subject to interference from carbamylated Hb (carb Hb). Carb Hb adducts are formed via interaction of terminal amino groups of HbA with isocyanic acid, after the spontaneous dissociation of urea to cyanate. It is hypothesized that a new immunoassay method, using a monoclonal antibody that recognizes the N-terminus of the Hb beta-chain and its sugar moiety, should be refractory to cross-reactive interference from carb Hb. To test this hypothesis, Hb was carbamylated in vitro and co-migration of carb Hb assessed with HbA1C using an electrophoretic method. Densitometric scans - post sodium cyanate incubation and electrophoretic separation - showed a 5 to 7 fold elevation of the HbA1C peak only, while HbA1C values obtained using immunoassay were unaffected. Also assessed was carbamylation interference in vivo, and a positive proportional bias with the electrophoretic system (Y) was observed compared to the immunoassay system (X) (y = 1.2x - 0.21 percent). Others have shown that carb Hb may cause a clinically significant false elevation in patient HbA1C values, when methods based on charge separation of Hb species are used. It is our conclusion, however, that while carb Hb may play a role, the differences observed in this study are largely due to calibration.

  17. Metastable Mesoscopic Clusters in Solutions of Sickle-Cell Hemoglobin

    PubMed Central

    Pan, Weichun; Galkin, Oleg; Filobelo, Luis; Nagel, Ronald L.; Vekilov, Peter G.

    2007-01-01

    Sickle cell hemoglobin (HbS) is a mutant, whose polymerization while in deoxy state in the venous circulation underlies the debilitating sickle cell anemia. It has been suggested that the nucleation of the HbS polymers occurs within clusters of dense liquid, existing in HbS solutions. We use dynamic light scattering with solutions of deoxy-HbS, and, for comparison, of oxy-HbS and oxy-normal adult hemoglobin, HbA. We show that solutions of all three Hb variants contain clusters of dense liquid, several hundred nanometers in size, which are metastable with respect to the Hb solutions. The clusters form within a few seconds after solution preparation and their sizes and numbers remain relatively steady for up to 3 h. The lower bound of the cluster lifetime is 15 ms. The clusters exist in broad temperature and Hb concentration ranges, and occupy 10−5–10−2 of the solution volume. The results on the cluster properties can serve as test data for a potential future microscopic theory of cluster stability and kinetics. More importantly, if the clusters are a part of the nucleation mechanism of HbS polymers, the rate of HbS polymerization can be controlled by varying the cluster properties. PMID:17040989

  18. Two new hemoglobin variants: Hb Aix-Les-Bains [β5(A2)Pro→Leu; HBB:c.17 C>T] and Hb Dubai [α122(H5)His→Leu (α2); HBA2:c.368 A>T].

    PubMed

    Joly, Philippe; Garcia, Caroline; Lacan, Philippe; Couprie, Nicole; Francina, Alain

    2011-01-01

    We report two new hemoglobin (Hb) variants; one causing an impairment of the N-terminal glycation of the β-globin chain and the other a hematological phenotype of α-thalassemia (α-thal). The first variant is Hb Aix-les-Bains [β5(A2)Pro→Leu] and the second Hb Dubai [α122(H5)His→Leu (α2)]. These two new Hb variants were detected by chromatographic and electrophoretic methods and characterized by molecular studies. Hb Dubai gives an α-thalassemic phenotype and should be routinely detected for preventing severe Hb H disease in couples at-risk for α-thal.

  19. Development and characterization of K562 cell clones expressing BCL11A-XL: Decreased hemoglobin production with fetal hemoglobin inducers and its rescue with mithramycin

    PubMed Central

    Finotti, Alessia; Gasparello, Jessica; Breveglieri, Giulia; Cosenza, Lucia Carmela; Montagner, Giulia; Bresciani, Alberto; Altamura, Sergio; Bianchi, Nicoletta; Martini, Elisa; Gallerani, Eleonora; Borgatti, Monica; Gambari, Roberto

    2015-01-01

    Induction of fetal hemoglobin (HbF) is considered a promising strategy in the treatment of β-thalassemia, in which production of adult hemoglobin (HbA) is impaired by mutations affecting the β-globin gene. Recent results indicate that B-cell lymphoma/leukemia 11A (BCL11A) is a major repressor of γ-globin gene expression. Therefore, disrupting the binding of the BCL11A transcriptional repressor complex to the γ-globin gene promoter provides a novel approach for inducing expression of the γ-globin genes. To develop a cellular screening system for the identification of BCL11A inhibitors, we produced K562 cell clones with integrated copies of a BCL11A-XL expressing vector. We characterized 12 K562 clones expressing different levels of BCL11A-XL and found that a clear inverse relationship does exist between the levels of BCL11A-XL and the extent of hemoglobinization induced by a panel of HbF inducers. Using mithramycin as an inducer, we found that this molecule was the only HbF inducer efficient in rescuing the ability to differentiate along the erythroid program, even in K562 cell clones expressing high levels of BCL11A-XL, suggesting that BCL11A-XL activity is counteracted by mithramycin. PMID:26342260

  20. HbA1c and Glycated Albumin Levels Are High in Gastrectomized Subjects with Iron-Deficiency Anemia.

    PubMed

    Inada, Shinya; Koga, Masafumi

    2017-01-01

    We report that glycated albumin (GA) is higher relative to HbA1c in non-diabetic, gastrectomized subjects without anemia, and thus is a sign of oxyhyperglycemia. It is known that gastrectomized subjects are prone to iron-deficiency anemia (IDA), and that the HbA1c levels of subjects with IDA are falsely high. In the present study, the HbA1c and GA levels of gastrectomized subjects with IDA were compared with gastrectomized subjects without anemia. Seven non-diabetic gastrectomized subjects with IDA were enrolled in the present study. Twenty-eight non-diabetic gastrectomized subjects without anemia matched with the subjects with IDA in terms of age, gender, and body mass index were used as the controls. Although there were no significant differences in fasting plasma glucose and OGTT 2-hour plasma glucose (2-h PG) between the two groups, the HbA1c and GA levels in gastrectomized subjects with IDA were significantly higher than the controls. For all of the gastrectomized subjects (n=35), ferritin exhibited a significant negative correlation with HbA1c and GA, and a significant positive correlation with 2-h PG. In addition, the HbA1c and GA levels exhibited a significant negative correlation with the mean corpuscular hemoglobin and hemoglobin. The HbA1c and GA levels in gastrectomized subjects with IDA were significantly higher than those in controls. The high GA levels are attributed to a tendency in which patients with total gastrectomy, who are prone to IDA, are susceptible to postprandial hyperglycemia and reactive hypoglycemia, which in turn leads to large fluctuations in plasma glucose.

  1. Quantitative measurement of HbA1c by an immunoturbidimetric assay compared to a standard HPLC method.

    PubMed

    Hamwi, A; Schweiger, C R; Veitl, M; Schmid, R

    1995-07-01

    Determination of hemoglobin A1c (HbA1c) is one of the most important monitoring procedures for long-term control of diabetes mellitus. Several analytical methods have been developed for the measurement of glycohemoglobin (GHb). Those most frequently used are ion-exchange chromatography for HbA1c and affinity chromatography for total GHb. In this study, a new turbidimetric immunoassay for HbA1c (Boehringer Mannheim, Germany) was evaluated that was performed on a Hitachi 911 clinical chemistry analyzer (Boehringer Mannheim). Good linearity in the range of 5% to 15% HbA1c, within-run and between-run coefficients of variation ranging from 2.4% to 5.9% were obtained. Results of 179 diabetic and nondiabetic patients showed good correlation to those of a routine HPLC method (r = 0.96). In addition, HbA2, HbS, and HbF in samples from nondiabetic patients were not detected by the immunoturbimetric assay and the "labile" HbA1c fraction (Schiff base) did not interfere with the new test.

  2. [Biological variation of glycation and mean blood glucose have greater influence on Hba1c levels in type 1 young diabetic patients than glucose instability].

    PubMed

    Abourazzak, Sana; Dorchy, Harry; Willems, Dominique; Melot, Christian

    2010-01-01

    The aim of the study was to assess the relative influence of mean blood glucose (MBG), glucose instability (GI) and biological variation of glycohemoglobin (BVG) on HbA1c. The study included 378 unselected young type 1 diabetic patients with a diabetes duration > 1 year. There were 1,409 visits with simultaneous HbA1c determinations and self-monitoring of BG meter downloads. GI was quantified by measuring the standard deviation (SD) of the recorded BG values. A statistical model was developed to predict HbA1c from MBG. Hemoglobin glycation index (HGI) was calculated (HGI = observed HbA1c--predicted HbA1c) for each visit to assess BVG based on the directional deviation of observed HbA1c from that predicted by MBG in the model. Afterwards, the population was divided by thirds into high-, moderate-, and low-HGI groups, i.e. high-, moderate-, and low-glycators, reflecting BVG. A total of 246,000 preprandial BG measurements were analysed, with a mean of 177 per visit. Grand MBG +/- SD was 171 +/- 40 mg/dl. Predicted HbA1c was calculated from the equation: 3.8399 + 0.0242 x MBG (r = 0.66; p < 0.0001). A MBG change of 40 mg/dl corresponded to 1% change in HbA1c, within the range 6-12%. Multiple regression analysis showed no significant relationship between SD and HbA1c, after adjustment for MBG. MBG was 10 times more important than SD to predict HbA1c. MBG was not statistically different between the high- and low glycators, but HbA1c was significantly different. Multiple linear regression was used to predict HbA1c from MBG, SD and BVG (measured by HGI), adjusted for age, duration, gender and ethnic origin. BVG and MBG had large influences on HbA1c, the impact of BVG being 84% of the impact of MBG. On the other hand, GI had only 17% of the impact of MBG. In conclusion the effect of BVG on HbA1c is independent and much greater that the influence attributable to GI. Hemoglobin glycation phenotype, responsible for BVG, may be important for the clinical assessment of diabetic

  3. Association of Estimated Glomerular Filtration Rate with Hemoglobin Level in Korean Adults: The 2010–2012 Korea National Health and Nutrition Examination Survey

    PubMed Central

    Han, Sang Youb; Oh, Se Won; Hong, Jae Won; Yi, Seong Yoon; Noh, Jung Hyun; Lee, Hye Ran; Kim, Dong-Jun

    2016-01-01

    Purpose Little is known about anemia in patients with early renal dysfunction. We aimed to investigate the association of hemoglobin level and anemia prevalence with estimated glomerular filtration rate (eGFR) decline using a nation-wide representative sample of the adult Korean population. Methods In total, 17,373 participants (7,296 men; weighted n = 18,330,187; mean age, 44.2±0.3 years; 9,886 women, weighted n = 18,317,454; mean age, 46.9±0.3 years) were included. eGFR was divided into 5 groups: Group 1, ≥105; Group 2, 90–104; 75–89; Group 4, 60–74; and Group 5, <60 mL/min/1.73m2. Results The weighted anemia prevalence rates were 2.6% in men and 12.8% in women. In men, the weighted hemoglobin level increased with a decrease in eGFR; this value peaked at an eGFR of 60–89 mL/min/1.73m2 and decreased thereafter at an eGFR of <60 mL/min/1.73m2 (15.19±0.03, 15.35±0.03, 15.53±0.03, 15.52±0.06, and 14.90±0.12 g/dL from Groups 1 to 5) after adjustment for age, college graduation, cancer history, current smoking, waist circumference, serum cholesterol level, serum triglyceride level, and diastolic blood pressure. In women, the weighted hemoglobin level increased with a decrease in eGFR; this value peaked with an eGFR of 75–89 mL/min/1.73m2 and decreased thereafter (12.90±0.03, 13.08±0.02, 13.20±0.04, 13.14±0.05, and 12.47±0.11 g/dL from Groups 1 to 5) after adjustment for menstruation, pregnancy, estrogen replacement, and the above-mentioned variables. In both sexes, the weighted prevalence of anemia with an eGFR of 60–104 mL/min/1.73m2 was significantly lower than that with an eGFR of ≥105 mL/min/1.73m2 (men, 3.2±0.4%, 1.9±0.3%, 1.8±0.3%, 2.0±0.9%, and 18.1±3.1%; women, 14.0±0.8%, 11.2±0.7%, 10.5±1.0%, 13.2±1.6%, and 32.3±3.2% from Groups 1 to 5). Conclusions We noted a compensatory increase in the hemoglobin level with a minor decline in kidney function (in the range of eGFR ≥60 mL/min/1.73m2) prior to a marked decrease in

  4. Severe α-Thalassemia Intermedia Due to a Compound Heterozygosity for the Highly Unstable Hb Adana (HBA2: c.179G>A) and a Novel Codon 24 (HBA2: c.75T>A) Mutation

    PubMed Central

    Megawati, Dewi; Nainggolan, Ita M.; Swastika, Maria; Susanah, Susi; Mose, Johanes C.; Harahap, Alida R.

    2014-01-01

    HBA2 We report a novel mutation at codon 24 of the α2-globin gene (HBA2: c.75T > A) found in a Sundanese family. This novel mutation was detected during prenatal diagnosis. The couple already had a 7-year-old boy who exhibited clinically severe α-thalassemia intermedia (α-TI), and he was found to be a compound heterozygote for the novel mutation at codon 24 and the previously described Hb Adana (HBA2: c.179G > A) at codon 59 of the α2-globin gene. The father was a carrier of the novel point mutation and showed normal hemoglobin (Hb) and a low mean corpuscular volume (MCV) and mean corpuscular Hb (MCH) value. PMID:24351118

  5. Impact of glutathione-HbA1c on HbA1c measurement in diabetes diagnosis via array isoelectric focusing, liquid chromatography, mass spectrometry and ELISA.

    PubMed

    Li, Si; Guo, Chen-Gang; Chen, Lu; Yin, Xiao-Yang; Wu, Yi-Xin; Fan, Liu-Yin; Fan, Hui-Zhi; Cao, Cheng-Xi

    2013-10-15

    Hemoglobin A1c (HbA1c) has been proven to be a key biomarker for diabetes screening, and glutathiolation of HbA1c (viz., GSS-HbA1c) has been identified. However, the impact of GSS-HbA1c on the measurement of HbA1c for diabetes screening has not been quantitatively assessed yet. To address the issue, the micropreparative capillary isoelectric focusing (cIEF) developed in our previous work was used for the high resolution separation and purification of hemoglobin (Hb) species. The main fractions of HbA0, HbA3 and HbA1c extracted from the developed cIEF were identified by validated Mono S method. The proposed GSS-HbA1c fractions in the cIEF were pooled and identified by electrospray ionization mass spectrometry (ESI-MS). The HbA1c enzyme-linked immunosorbent assay (ELISA) kit was employed for further quantitative analysis of GSS-HbA1c. A total of 34 blood samples with HbA1c levels from 4.2% to 13.4% were assessed via the above comprehensive strategy of IEF-HPLC-MS-ELISA. It was demonstrated that the HbA1c levels detected by cation exchange LC were considerably influenced by the glutathiolation of Hb and the range of detected GSS-HbA1c values was between 0.23% and 0.74%. The results and developed cIEF methods have considerable significances for investigation of diabetes and clinical diagnosis.

  6. Genome annotation of a 1.5 Mb region of human chromosome 6q23 encompassing a quantitative trait locus for fetal hemoglobin expression in adults

    PubMed Central

    Close, James; Game, Laurence; Clark, Barnaby; Bergounioux, Jean; Gerovassili, Ageliki; Thein, Swee Lay

    2004-01-01

    Background Heterocellular hereditary persistence of fetal hemoglobin (HPFH) is a common multifactorial trait characterized by a modest increase of fetal hemoglobin levels in adults. We previously localized a Quantitative Trait Locus for HPFH in an extensive Asian-Indian kindred to chromosome 6q23. As part of the strategy of positional cloning and a means towards identification of the specific genetic alteration in this family, a thorough annotation of the candidate interval based on a strategy of in silico / wet biology approach with comparative genomics was conducted. Results The ~1.5 Mb candidate region was shown to contain five protein-coding genes. We discovered a very large uncharacterized gene containing WD40 and SH3 domains (AHI1), and extended the annotation of four previously characterized genes (MYB, ALDH8A1, HBS1L and PDE7B). We also identified several genes that do not appear to be protein coding, and generated 17 kb of novel transcript sequence data from re-sequencing 97 EST clones. Conclusion Detailed and thorough annotation of this 1.5 Mb interval in 6q confirms a high level of aberrant transcripts in testicular tissue. The candidate interval was shown to exhibit an extraordinary level of alternate splicing – 19 transcripts were identified for the 5 protein coding genes, but it appears that a significant portion (14/19) of these alternate transcripts did not have an open reading frame, hence their functional role is questionable. These transcripts may result from aberrant rather than regulated splicing. PMID:15169551

  7. Molecular mechanisms of human hemoglobin switching: selective undermethylation and expression of globin genes in embryonic, fetal, and adult erythroblasts.

    PubMed Central

    Mavilio, F; Giampaolo, A; Carè, A; Migliaccio, G; Calandrini, M; Russo, G; Pagliardi, G L; Mastroberardino, G; Marinucci, M; Peschle, C

    1983-01-01

    The globin chain synthetic pattern and the extent of DNA methylation within embryonic, fetal, and adult beta-like globin gene domains were evaluated in greater than or equal to 90% purified human erythroblasts from yolk sacs and fetal livers in the 6- to 12-wk gestational period as well as from adult marrows. The 6-wk erythroblasts produce essentially embryonic epsilon chains, whereas the 12-wk erythroblasts synthesize largely fetal gamma globin and the adult marrow erythroblasts synthesize almost exclusively adult beta chains. In all phases of ontogenic development, a strong correlation exists between DNA hypomethylation in the close flanking sequences of globin genes and their expression. These results suggest that modulation of the methylation pattern may represent a key mechanism for regulating expression of human globin genes during embryonic leads to fetal and fetal leads to adult Hb switches in humans. In ontogenic development this mechanism might in turn correlate with a gradual modification of chromatin structure in the non-alpha gene cluster, thus leading to a 5' leads to 3' activation of globin genes in a balanced fashion. Images PMID:6316333

  8. Hemoglobin C disease

    MedlinePlus

    Clinical hemoglobin C ... Hemoglobin C is an abnormal type of hemoglobin, the protein in red blood cells that carries oxygen. It is a type of hemoglobinopathy. The disease is caused by a problem with ...

  9. Development of hemoglobin A1c certified reference material by liquid chromatography isotope dilution mass spectrometry.

    PubMed

    Bi, Jiaming; Wu, Liqing; Yang, Bin; Yang, Yi; Wang, Jing

    2012-04-01

    We report the development of a National Institute of Metrology (NIM) hemoglobin A(1c) (HbA(1c)) certified reference material (CRM). Each CRM unit contains about 10 μL of hemoglobin. Both hemoglobin and glycated hemoglobin were quantitatively determined by high-performance liquid chromatography (HPLC)-isotope dilution mass spectrometry (IDMS) with synthesized VHLTPE and glycated VHLTPE as standards. The mass fraction of synthesized VHLTPE or glycated VHLTPE was also quantitatively determined by HPLC-IDMS with NIM amino acid CRMs as standards. The homogeneity and stability of the CRMs were examined with a commercial HbA(1c) analyzer based on the HPLC principle. Fifteen units were randomly selected for homogeneity examination, and statistical analysis showed there was no inhomogeneity. Examination of the stability showed that the CRM was stable for at least 6 months at -80 °C. Uncertainty components of the balance, amino acid purity, hydrolysis and proteolysis efficiency, method reproducibility, homogeneity, and stability were taken into consideration for uncertainty evaluation. The certified value of NIM HbA(1c) CRM was expressed as the ratio of HbA(1c) to total hemoglobin in moles, and was (9.6 ± 1.9)%. The CRM can be used as a calibration or validation standard for clinical diagnostics. It is expected to improve the comparability for HbA(1c) measurement in China.

  10. A field effect transistor (FET)-based immunosensor for detection of HbA1c and Hb.

    PubMed

    Bian, Chao; Tong, Jianhua; Sun, Jizhou; Zhang, Hong; Xue, Qiannan; Xia, Shanhong

    2011-04-01

    A field effect transistor (FET)-based immunosensor was developed for diabetes monitoring by detecting the concentrations of glycated hemoglobin (HbA1c) and hemoglobin (Hb). This immunosensor consists of a FET-based sensor chip and a disposable extended-gate electrode chip. The sensor chip was fabricated by standard CMOS process and was integrated with signal readout circuit. The disposable electrode chip, fabricated on polyester plastic board by Micro-Electro-Mechanical-Systems (MEMS) technique, was integrated with electrodes array and micro reaction pool. Biomolecules were immobilized on the electrode based on self-assembled monolayer and gold nanoparticles. Experimental results showed that the immunosensor achieved a linear response to HbA1c with the concentration from 4 to 24 μg/ml, and a linear response to Hb with the concentration from 60 to 180 μg/ml.

  11. Hemoglobin Ypsilanti: a high-oxygen-affinity hemoglobin demonstrated by two automated high-pressure liquid chromatography systems.

    PubMed

    Mais, Daniel D; Boxer, Laurence A; Gulbranson, Ronald D; Keren, David F

    2007-11-01

    Hemoglobin (Hb) Ypsilanti is a rare high-oxygen-affinity hemoglobin. Like other high-oxygen-affinity hemoglobins, Hb Ypsilanti manifests as erythrocytosis. Because the migration of many high-oxygen-affinity variants on alkaline and acid gels does not differ from that of HbA, oxygen-hemoglobin dissociation studies are often used to document their presence. Hb Ypsilanti is a notable exception because its electrophoresis pattern on alkaline gel is highly characteristic, exemplifying the phenomenon of hybrid formation in variant hemoglobins. In the past few years, several laboratories have begun to use high-pressure liquid chromatography (HPLC) as a screen for hemoglobinopathies. We demonstrate the elution profile of Hb Ypsilanti on the 2 most widely used HPLC methods.

  12. Hemoglobin A1c in predicting progression to diabetes.

    PubMed

    Nakagami, Tomoko; Tajima, Naoko; Oizumi, Toshihide; Karasawa, Shigeru; Wada, Kiriko; Kameda, Wataru; Susa, Shinji; Kato, Takeo; Daimon, Makoto

    2010-01-01

    The predictive value of hemoglobin A1c (HbA1c) in comparison to fasting plasma glucose (FPG) is evaluated for 5-year incident diabetes (DM), as HbA1c may be more practical than FPG in the screening for DM in the future. Of 1189 non-DM subjects aged 35-89 years old from the Funagata Study, 57 subjects (4.8%) had developed DM on the WHO criteria at 5-year follow-up. The odds ratio (95% confidence interval: CI) for a one standard deviation increase in FPG/HbA1c was 3.40 (2.44-4.74)/3.49 (2.42-5.02). The area under the receiver operating characteristic curve for FPG/HbA1c was 0.786 (95% CI: 0.719-0.853)/0.785 (0.714-0.855). The HbA1c corresponding to FPG 5.56 mmol/l was HbA1c 5.3%. There was no statistical difference in sensitivity between FPG 5.56 mmol/l and HbA1c 5.3% (61.4% vs. 56.1%), while specificity was higher in HbA1c 5.3% than FPG 5.56 mmol/l (87.8% vs. 82.5%, p-value<0.001). The fraction of incident case from those with baseline IGT was similar between the groups, however the fraction of people above the cut-off was significantly lower in HbA1c 5.3% than FPG 5.56 mmol/l (14.3% vs. 19.6%, p-value<0.001). HbA1c is similar to FPG to evaluate DM risk, and HbA1c could be practical and efficient to select subjects for intervention.

  13. 24 CFR 904.305 - Funding of HBA.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 24 Housing and Urban Development 4 2012-04-01 2012-04-01 false Funding of HBA. 904.305 Section 904... LOW RENT HOUSING HOMEOWNERSHIP OPPORTUNITIES Homebuyers Association (HBA) § 904.305 Funding of HBA. (a... HUD. Such contributions shall be subject to whatever restrictions are applied by HUD to the funding...

  14. 24 CFR 904.305 - Funding of HBA.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 24 Housing and Urban Development 4 2013-04-01 2013-04-01 false Funding of HBA. 904.305 Section 904... LOW RENT HOUSING HOMEOWNERSHIP OPPORTUNITIES Homebuyers Association (HBA) § 904.305 Funding of HBA. (a... HUD. Such contributions shall be subject to whatever restrictions are applied by HUD to the funding...

  15. Pediatric diabetes consortium type 1 diabetes new onset (NeOn) study: Factors associated with HbA1c levels one year after diagnosis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    To identify determinants of hemoglobin A1c (HbA1c) levels 1 yr after the diagnosis of type 1 diabetes (T1D) in participants in the Pediatric Diabetes Consortium (PDC) T1D New Onset (NeOn) Study. Diabetes-specific as well as socioeconomic factors during the first year following diagnosis were analyze...

  16. Effect of Iron Deficiency Anemia on Hemoglobin A1c Levels

    PubMed Central

    Sinha, Nitin; Mishra, T.K.; Singh, Tejinder

    2012-01-01

    Background Iron deficiency anemia is the most common form of anemia in India. Hemoglobin A1c (HbA1c) is used in diabetic patients as an index of glycemic control reflecting glucose levels of the previous 3 months. Like blood sugar levels, HbA1c levels are also affected by the presence of variant hemoglobins, hemolytic anemias, nutritional anemias, uremia, pregnancy, and acute blood loss. However, reports on the effects of iron deficiency anemia on HbA1c levels are inconsistent. We conducted a study to analyze the effects of iron deficiency anemia on HbA1c levels and to assess whether treatment of iron deficiency anemia affects HbA1c levels. Methods Fifty patients confirmed to have iron deficiency anemia were enrolled in this study. HbA1c and absolute HbA1c levels were measured both at baseline and at 2 months after treatment, and these values were compared with those in the control population. Results The mean baseline HbA1c level in anemic patients (4.6%) was significantly lower than that in the control group (5.5%, p<0.05). A significant increase was observed in the patients' absolute HbA1c levels at 2 months after treatment (0.29 g/dL vs. 0.73 g/dL, p<0.01). There was a significant difference between the baseline values of patients and controls (0.29 g/dL vs. 0.74 g/dL, p<0.01). Conclusions In contrast to the observations of previous studies, ours showed that HbA1c levels and absolute HbA1c levels increased with treatment of iron deficiency anemia. This could be attributable to nutritional deficiency and/or certain unknown variables. Further studies are warranted. PMID:22259774

  17. Hemoglobin allostery: new views on old players.

    PubMed

    Miele, Adriana Erica; Bellelli, Andrea; Brunori, Maurizio

    2013-05-13

    Proteins are dynamic molecular machines whose structure and function are modulated by environmental perturbations and natural selection. Allosteric regulation, discovered in 1963 as a novel molecular mechanism of enzymatic adaptation [Monod, Changeux & Jacob (1963). J. Mol. Biol.6, 306-329], seems to be the leit motiv of enzymes and metabolic pathways, enabling fine and quick responses toward external perturbations. Hemoglobin (Hb), the oxygen transporter of all vertebrates, has been for decades the paradigmatic system to test the validity of the conformational selection mechanism, the conceptual innovation introduced by Monod, Wyman and Changeux. We present hereby the results of a comparative analysis of structure, function and thermodynamics of two extensively investigated hemoglobins: human HbA and trout HbI. They represent a unique and challenging comparison to test the general validity of the stereochemical model proposed by Perutz. Indeed both proteins are ideal for the purpose being very similar yet very different. In fact, T-HbI is a low-ligand-affinity cooperative tetrameric Hb, insensitive to all allosteric effectors. This remarkable feature, besides being physiologically sound, supports the stereochemical model, given that the six residues identified in HbA as responsible for the Bohr and the 2,3-di-phosphoglycerate effects are all mutated. Comparison of the three-dimensional structures of HbA and T-HbI allows unveiling the molecular mechanism whereby the latter has a lower O2 affinity. Moreover, the energetic balance sheet shows that the salt bridges breaking upon allosteric quaternary transition are important yet insufficient to account for the free energy of heme-heme interactions in both hemoglobins.

  18. A Review on Glycosylated Hemoglobin in Polycystic Ovary Syndrome.

    PubMed

    Rezaee, Mohsen; Asadi, Nasrin; Pouralborz, Yasna; Ghodrat, Mahshid; Habibi, Shaghayegh

    2016-12-01

    Polycystic ovary syndrome (PCOS) is one of the most common reproductive endocrine disorders among women of reproductive age, with a variety of complications and consequences mostly due to hyperandrogenism and insulin resistance (IR). PCOS patients with IR are at risk for metabolic syndrome and diabetes mellitus (DM) along with its complications such as cardiovascular events. There are several methods for screening IR in patients with PCOS to predict DM and other complications. Fasting plasma glucose test, oral glucose tolerance test, and insulin and glycosylated hemoglobin (HbA1c) levels are some available screening tools for IR. The American Diabetes Association recommended HbA1c to screen for DM because HbA1c is not affected by day-to-day plasma glucose levels and reflects the plasma glucose status during 2-3 months before measurement. Some studies have evaluated the role of HbA1c as a screening method to predict DM in PCOS patients, however, there are still controversies in this matter. Also some studies reported that HbA1c has a correlation with complications of PCOS such as metabolic syndrome and cardiovascular events. We found that HbA1c could be a suitable screening test for IR in PCOS patients but more studies are recommended, omitting confounding factors that could affect IR in patients with PCOS, such as antihyperglycemic agents like metformin, or lifestyle modification, which can be effective in reducing IR in patients with PCOS.

  19. Production of β-globin and adult hemoglobin following G418 treatment of erythroid precursor cells from homozygous β039 thalassemia patients

    PubMed Central

    Salvatori, Francesca; Breveglieri, Giulia; Zuccato, Cristina; Finotti, Alessia; Bianchi, Nicoletta; Borgatti, Monica; Feriotto, Giordana; Destro, Federica; Canella, Alessandro; Brognara, Eleonora; Lampronti, Ilaria; Breda, Laura; Rivella, Stefano; Gambari, Roberto

    2013-01-01

    In several types of thalassemia (including β039-thalassemia), stop codon mutations lead to premature translation termination and to mRNA destabilization through nonsense-mediated decay. Drugs (for instance aminoglycosides) can be designed to suppress premature termination, inducing a ribosomal readthrough. These findings have introduced new hopes for the development of a pharmacologic approach to the cure of this disease. However, the effects of aminoglycosides on globin mRNA carrying β-thalassemia stop mutations have not yet been investigated. In this study, we have used a lentiviral construct containing the β039- thalassemia globin gene under control of the β-globin promoter and a LCR cassette. We demonstrated by fluorescence-activated cell sorting (FACS) analysis the production of β-globin by K562 cell clones expressing the β039-thalassemia globin gene and treated with G418. More importantly, after FACS and high-performance liquid chromatography (HPLC) analyses, erythroid precursor cells from β039-thalassemia patients were demonstrated to be able to produce β-globin and adult hemoglobin after treatment with G418. This study strongly suggests that ribosomal readthrough should be considered a strategy for developing experimental strategies for the treatment of β0-thalassemia caused by stop codon mutations. PMID:19810011

  20. Visceral fat area is associated with HbA1c but not dialysate-related glucose load in nondiabetic PD patients

    NASA Astrophysics Data System (ADS)

    Ho, Li-Chun; Yen, Chung-Jen; Chao, Chia-Ter; Chiang, Chih-Kang; Huang, Jenq-Wen; Hung, Kuan-Yu

    2015-08-01

    Factors associated with increased visceral fat area (VFA) have been well documented in the general population but rarely explored in nondiabetic individuals on peritoneal dialysis (PD). As glycosylated hemoglobin (HbA1c) is positively correlated with VFA in diabetic patients, we hypothesized that the same correlation would exist in nondiabetic PD patients. We enrolled 105 nondiabetic patients who had undergone chronic PD for more than 3 months. Each subject underwent an abdominal computed tomography (CT) scan, and the umbilicus cut was analyzed for VFA. VFA values, corrected for body mass index and subjected to natural logarithm transformations, were examined to determine whether they were correlated with HbA1c and other parameters. PD dialysates prescribed at the time of enrollment were recorded to calculate glucose load. We found that when 105 nondiabetic PD patients were classified according to tertiles of HbA1c, higher HbA1c was associated with larger VFA. Multiple linear regression analysis revealed that HbA1c was an independent determinant of VFA, while glucose load and other PD-specific factors were not. In summary, HbA1c, but not PD-related glucose load, was positively correlated with VFA in nondiabetic PD patients, suggesting clinical utility of HbA1c in the PD population.

  1. Efficacy of metabolic surgery on HbA1c decrease in type 2 diabetes mellitus patients with BMI <35 kg/m2--a review.

    PubMed

    Ngiam, Kee Yuan; Lee, Wei-Jei; Lee, Yi-Chih; Cheng, Anton

    2014-01-01

    High glycated hemoglobin A1c (HbA1c) is strongly correlated with developing type 2 diabetes mellitus (T2DM) complications; this study reviews the efficacy of various types of metabolic surgeries in reducing HbA1c levels in type 2 diabetics with BMI <35 kg/m(2). An electronic search of MEDLINE databases using terms 'metabolic surgery', type 2 diabetes mellitus, BMI <35 kg/m(2), and related keywords for studies published between 1987 and 2013. Data from 53 articles with 2,258 patients were selected for this review. The weighted mean change in HbA1c was -2.8 % (95 % CI -2.8 to -2.7, p < 0.01) and weighted mean BMI change was -5.5 kg/m(2) (95 % CI -5.6 to -5.4, p < 0.01). There was a strong correlation between weighted percentage mean change in HbA1c and BMI. Adjustable gastric banding and duodenal jejunal bypass were inferior to other surgeries in reducing BMI and HbA1c in BMI <35 kg/m(2). Metabolic surgery significantly decreases HbA1c in T2DM patients with BMI <35 kg/m(2) and that the magnitude of HbA1c change may be a useful surrogate of DM control.

  2. Universal metastability of sickle hemoglobin polymerization

    NASA Astrophysics Data System (ADS)

    Weng, Weijun

    Sickle hemoglobin (HbS) is a natural mutation of the normal hemoglobin (HbA) found in the red blood cells of human body. Polymerization of HbS occurs when the concentration of deoxyHbS exceeds a well-defined solubility, which is the underlying cause of the Sickle Cell Disease. It has long been assumed that thermodynamic equilibrium is reached when polymerization comes to an end. However, in this thesis we demonstrate that in confined volume as well as in bulk solution, HbS polymerization terminates prematurely, leaving the solution in a metastable state. A newly developed Reservoir method as well as modulated excitation method were adopted for the study. This discovery of universal metastability gives us new insights into understanding the mechanism of sickle cell disease.

  3. Inpatient HbA1c testing: a prospective observational study

    PubMed Central

    Nanayakkara, Natalie; Nguyen, Hang; Churilov, Leonid; Kong, Alvin; Pang, Nyuk; Hart, Graeme K; Owen-Jones, Elizabeth; White, Jennifer; Ross, Jane; Stevenson, Victoria; Bellomo, Rinaldo; Lam, Que; Crinis, Nicholas; Robbins, Raymond; Johnson, Doug; Baker, Scott T; Zajac, Jeffrey D; Ekinci, Elif I

    2015-01-01

    Objective To use admission inpatient glycated hemoglobin (HbA1c) testing to help investigate the prevalence of unrecognized diabetes, the cumulative prevalence of unrecognized and known diabetes, and the prevalence of poor glycemic control in both. Moreover, we aimed to determine the 6-month outcomes for these patients. Finally, we aimed to assess the independent association of diabetes with these outcomes. Research, design, and methods Prospective observational cohort study conducted in a tertiary hospital in Melbourne, Australia. Patients A cohort of 5082 inpatients ≥54 years admitted between July 2013 and January 2014 underwent HbA1c measurement. A previous diagnosis of diabetes was obtained from the hospital medical record. Patient follow-up was extended to 6 months. Results The prevalence of diabetes (known and unrecognized) was 34%. In particular, we identified that unrecognized but HbA1c-confirmed diabetes in 271 (5%, 95% CI 4.7% to 6.0%) patients, previously known diabetes in 1452 (29%, 95% CI 27.3% to 29.8%) patients; no diabetes in 3359 (66%, 95% CI 64.8–67.4%) patients. Overall 17% (95% CI 15.3% to 18.9%) of patients with an HbA1c of >6.5% had an HbA1c ≥8.5%. After adjusting for age, gender, Charlson Index score, estimated glomerular filtration rate, and hemoglobin levels, with admission unit treated as a random effect, patients with previously known diabetes had lower 6-month mortality (OR 0.69, 95% CI 0.56 to 0.87, p=0.001). However, there were no significant differences in proportions of intensive care unit admission, mechanical ventilation or readmission within 6 months between the 3 groups. Conclusions Approximately one-third of all inpatients ≥54 years of age admitted to hospital have diabetes of which about 1 in 6 was previously unrecognized. Moreover, poor glycemic control was common. Proportions of intensive care unit admission, mechanical ventilation, or readmission were similar between the groups. Finally, diabetes was

  4. [Sickle cell syndrome. Association between hemoglobin S and β thalassemia].

    PubMed

    Gasparini, Nehuen P; Agriello, Evangelina E; Zanella, M J Lorena; Iommi, María P; Maradei, Juan; Sandoval, Marisa J

    2016-01-01

    Sickle cell syndrome HbS/β thalassemia is an inheritable mendelian type disease where two affected alleles are simultaneously present, one from HbS (βS) and the other from β thalassemia. That situation is mainly linked to individuals who share African and Mediterranean ancestors. The mutation responsible for HbS is a point mutation, whereas for β thalassemia, there are more than 200 mutations that cause different degrees of deficiency synthesis of β globin chain, which justifies the clinical and genetic heterogeneity of this syndrome. It is presented a clinical case of a young adult man with limited resources that consulted by longstanding bone pain. The patient presented anemia with a marked microcytosis. Hemoglobin electrophoresis was performed, an abnormal peak in position of HbS and high HbA2 fraction were detected. These last results indicated two possible molecular alterations simultaneously, for this reason the molecular study was performed looking for the most common β thalassemia mutations in our population and, the point mutation responsible for S hemoglobinopathy. Clinical data and biochemical laboratory allowed the diagnosis of sickle cell syndrome. The molecular study confirmed the syndrome carrying mutations IVS-I nt 110 G > A, responsible for β thalassemia and, codon 6 A > T (GAG → GTG: Glu → Val) responsible for S hemoglobinophaty. Since it is a disease of high health impact, it is important to provide genetic counseling to the whole family.

  5. Glycated Hemoglobin Levels in Patients with Decompensated Cirrhosis

    PubMed Central

    Satapathy, Sanjaya K.

    2016-01-01

    Introduction. Aim of this study is to determine if HbA1c levels are a reliable predictor of glycemic control in patients with decompensated cirrhosis. Methods. 200 unique patients referred for liver transplantation at University of Tennessee/Methodist University Transplant Institute with a HbA1c result were included. Three glucose levels prior to the “measured” A1c (MA1c) were input into an HbA1c calculator from the American Diabetes Association website to determine the “calculated” A1c (CA1c). The differences between MA1c and CA1c levels were computed. Patients were divided into three groups: group A, difference of <0.5; group B, 0.51–1.5; and group C, >1.5. Results. 97 (49%) patients had hemoglobin A1c of less than 5%. Discordance between calculated and measured HbA1c of >0.5% was seen in 47% (n = 94). Higher level of discordance of greater than >1.5 was in 12% of patients (n = 24). Hemoglobin was an independent predictor for higher discordance (odds ratio 0.77 95%, CI 0.60–0.99, and p value 0.04). HbA1c was an independent predictor of occurrence of HCC (OR 2.69 955, CI 1.38–5.43, and p value 0.008). Conclusion. HbA1c is not a reliable predictor of glycemic control in patients with decompensated cirrhosis, especially in those with severe anemia. PMID:27882051

  6. Value of the combined examination of Cys-C and HbA1c for diagnosis of early renal injury in pediatric diabetes

    PubMed Central

    Qian, Tong; Tian, Lijun; Li, Yanyan; Zhang, Zhenru; Tian, Xiuying; Sun, Dan

    2017-01-01

    The objective of the present study was to evaluate the combined application of measuring cystatin C (Cys-C) and hemoglobin A1c (HbA1c) levels for early renal injury in pediatric patients with type 2 diabetes. A total of 130 children with type 2 diabetes admitted to our hospital from May 2013 to July 2015 were selected. Patients were divided according to whether there was complication of renal injury. In group A (n=65), the patients had renal injury and in group B (n=65), the patients did not have renal injury. The levels of Cys-C and HbA1c in the two groups were examined. The results showed that the levels of Cys-C and HbA1c of patients in group A were significantly higher than those in group B (P<0.05), and the positive rate of the combined examination of Cys-C and HbA1c in group A was 92.3%, and was higher than that of the individual examinations of either Cys-C or HbA1c (P<0.05). The Spearman's correlation coefficient analysis was applied to group B and showed that Cys-C was positively correlated with HbA1c (r=0.842, P<0.05). From analysis of the receiver operating characteristic curves, the combined examination of Cys-C and HbA1c surpassed the individual examinations of Cys-C or HbA1c in sensitivity and specificity (P<0.05). In conclusion, the positive detection rate of early renal injury was significantly increased by the combined examination of Cys-C and HbA1c in pediatric patients with type 2 diabetes, which is beneficial for early identification and diagnosis of this diseases and is worthy of clinical application.

  7. HbA1c as a Screening tool for Ketosis in Patients with Type 2 Diabetes Mellitus

    PubMed Central

    Zhu, Bing; Bu, Le; Zhang, Manna; Gusdon, Aaron M.; Zheng, Liang; Rampersad, Sharvan; Li, Jue; Qu, Shen

    2016-01-01

    Ketosis in patients with type 2 diabetes mellitus (T2DM) is overlooked due to atypical symptoms. The objective of this study is to evaluate the value of hemoglobin A1c (HbA1c) as a screening tool for ketosis in T2DM patients. This retrospective study consisted of 253 T2DM patients with ketosis at Shanghai 10th People’s Hospital during a period from January 1, 2011 to June 30, 2015. A control group consisted of 221 T2DM patients without ketosis randomly selected from inpatients during the same period. Receiver operating characteristic curve (ROC) analysis was used to examine the sensitivity and specificity of HbA1c as an indicator for ketosis. Higher HbA1c levels were correlated with ketosis. In patients with newly diagnosed T2DM, the area under the curve (AUC) was 0.832, with 95% confidence interval (CI) 0.754–0.911. The optimal threshold was 10.1% (87 mmol/mol). In patients with previously diagnosed T2DM, the AUC was 0.811 (95% CI: 0.767–0.856), with an optimal threshold of 8.6% (70 mmol/mol). HbA1c is a potential screening tool for ketosis in patients with T2DM. Ketosis is much more likely with HbA1c values at ≥10.1% in patients with newly diagnosed T2DM and HbA1c values at ≥8.6% in patients with previously diagnosed T2DM. PMID:28009017

  8. ICSH recommendations for assessing automated high-performance liquid chromatography and capillary electrophoresis equipment for the quantitation of HbA2.

    PubMed

    Stephens, A D; Colah, R; Fucharoen, S; Hoyer, J; Keren, D; McFarlane, A; Perrett, D; Wild, B J

    2015-10-01

    Automated high performance liquid chromatography and Capillary electrophoresis are used to quantitate the proportion of Hemoglobin A2 (HbA2 ) in blood samples order to enable screening and diagnosis of carriers of β-thalassemia. Since there is only a very small difference in HbA2 levels between people who are carriers and people who are not carriers such analyses need to be both precise and accurate. This paper examines the different parameters of such equipment and discusses how they should be assessed.

  9. Interactions of hemoglobin in live red blood cells measured by the electrophoresis release test.

    PubMed

    Su, Yan; Gao, Lijun; Ma, Qiang; Zhou, Lishe; Qin, Liangyi; Han, Lihong; Qin, Wenbin

    2010-09-01

    To elucidate the protein-protein interactions of hemoglobin (Hb) variants A and A(2), HbA was first shown to bind with HbA(2) in live red blood cells (RBCs) by diagonal electrophoresis and then the interaction between HbA and HbA(2) outside the RBC was shown by cross electrophoresis. The starch-agarose gel electrophoresis of hemolysate, RBCs, freeze-thawed RBCs and the supernatant of freeze-thawed RBCs showed that the interaction between HbA and HbA(2) was affected by membrane integrity. To identify the proteins involved in the interaction, protein components located between HbA and HbA(2) in RBCs (RBC HbA-HbA(2)) and hemolysate (hemolysate HbA-HbA(2)) were isolated from the starch-agarose gel and separated by 5-12% SDS-PAGE. The results showed that there was a ≈22 kDa protein band located in the RBC HbA-HbA(2) but not in hemolysate HbA-HbA(2). Sequencing by LC/MS/MS showed that this band was a protein complex that included mainly thioredoxin peroxidase B, α-globin, δ-globin and β-globin. Thus, using our unique in vivo whole blood cell electrophoresis release test, Hbs were proven for the first time to interact with other proteins in the live RBC.

  10. Association of high normal HbA1c and TSH levels with the risk of CHD: a 10-year cohort study and SVM analysis

    PubMed Central

    Li, Hui; Cui, Ying; Zhu, Yanan; Yan, Haiying; Xu, Wenge

    2017-01-01

    This study aimed to determine the association between the clinical reference range of serum glycated hemoglobin A1c (HbA1c) and thyrotropin (TSH) and the risk of coronary heart disease (CHD) in non-diabetic and euthyroid patients. We examined baseline HbA1c and TSH in 538 healthy participants, and then analyzed the associations and potential value of these indicators for predicting CHD using Cox proportional hazard and support vector machine analyses. During the median follow-up of 120 months, 39 participants later developed CHD. The baseline HbA1c and TSH within the reference range were positively associated with CHD risk. No correlation and interaction were found between the baseline HbA1c and TSH for the development of CHD. Disease event-free survival varied among participants with different baseline HbA1c quintiles, whereas disease event-free survival was similar for different TSH tertiles. The combination of these baselines showed sensitivity of 87.2%, specificity of 92.7%, and accuracy of 92.3% for identifying the participants who will later develop CHD. Relatively high but clinically normal HbA1c and TSH levels may increase the risk of CHD. Therefore, the combination of these indicators can serve as a biomarker for identifying healthy individuals from those who would later develop CHD. PMID:28345646

  11. Association of high normal HbA1c and TSH levels with the risk of CHD: a 10-year cohort study and SVM analysis.

    PubMed

    Li, Hui; Cui, Ying; Zhu, Yanan; Yan, Haiying; Xu, Wenge

    2017-03-27

    This study aimed to determine the association between the clinical reference range of serum glycated hemoglobin A1c (HbA1c) and thyrotropin (TSH) and the risk of coronary heart disease (CHD) in non-diabetic and euthyroid patients. We examined baseline HbA1c and TSH in 538 healthy participants, and then analyzed the associations and potential value of these indicators for predicting CHD using Cox proportional hazard and support vector machine analyses. During the median follow-up of 120 months, 39 participants later developed CHD. The baseline HbA1c and TSH within the reference range were positively associated with CHD risk. No correlation and interaction were found between the baseline HbA1c and TSH for the development of CHD. Disease event-free survival varied among participants with different baseline HbA1c quintiles, whereas disease event-free survival was similar for different TSH tertiles. The combination of these baselines showed sensitivity of 87.2%, specificity of 92.7%, and accuracy of 92.3% for identifying the participants who will later develop CHD. Relatively high but clinically normal HbA1c and TSH levels may increase the risk of CHD. Therefore, the combination of these indicators can serve as a biomarker for identifying healthy individuals from those who would later develop CHD.

  12. 24 CFR 904.304 - Functions of the HBA.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 24 Housing and Urban Development 4 2014-04-01 2014-04-01 false Functions of the HBA. 904.304 Section 904.304 Housing and Urban Development REGULATIONS RELATING TO HOUSING AND URBAN DEVELOPMENT... DEVELOPMENT LOW RENT HOUSING HOMEOWNERSHIP OPPORTUNITIES Homebuyers Association (HBA) § 904.304 Functions...

  13. 24 CFR 904.304 - Functions of the HBA.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 24 Housing and Urban Development 4 2012-04-01 2012-04-01 false Functions of the HBA. 904.304 Section 904.304 Housing and Urban Development REGULATIONS RELATING TO HOUSING AND URBAN DEVELOPMENT... DEVELOPMENT LOW RENT HOUSING HOMEOWNERSHIP OPPORTUNITIES Homebuyers Association (HBA) § 904.304 Functions...

  14. 24 CFR 904.304 - Functions of the HBA.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 24 Housing and Urban Development 4 2011-04-01 2011-04-01 false Functions of the HBA. 904.304 Section 904.304 Housing and Urban Development REGULATIONS RELATING TO HOUSING AND URBAN DEVELOPMENT... DEVELOPMENT LOW RENT HOUSING HOMEOWNERSHIP OPPORTUNITIES Homebuyers Association (HBA) § 904.304 Functions...

  15. Diabetes mellitus, hemoglobin A1C, and the incidence of total joint arthroplasty infection.

    PubMed

    Iorio, Richard; Williams, Kelly M; Marcantonio, Andrew J; Specht, Lawrence M; Tilzey, John F; Healy, William L

    2012-05-01

    Patients with diabetes have a higher incidence of infection after total joint arthroplasty (TJA) than patients without diabetes. Hemoglobin A1c (HbA1c) levels are a marker for blood glucose control in diabetic patients. A total of 3468 patients underwent 4241 primary or revision total hip arthroplasty or total knee arthroplasty at one institution. Hemoglobin A1c levels were examined to evaluate if there was a correlation between the control of HbA1c and infection after TJA. There were a total of 46 infections (28 deep and 18 superficial [9 cellulitis and 9 operative abscesses]). Twelve (3.43%) occurred in diabetic patients (n = 350; 8.3%) and 34 (0.87%) in nondiabetic patients (n = 3891; 91.7%) (P < .001). There were 9 deep (2.6%) infections in diabetic patients and 19 (0.49%) in nondiabetic patients. In noninfected, diabetic patients, HbA1c level ranged from 4.7% to 15.1% (mean, 6.92%). In infected diabetic patients, HbA1c level ranged from 5.1% to 11.7% (mean, 7.2%) (P < .445). The average HbA1c level in patients with diabetes was 6.93%. Diabetic patients have a significantly higher risk for infection after TJA. Hemoglobin A1c levels are not reliable for predicting the risk of infection after TJA.

  16. Blood pressure reduction due to hemoglobin glycosylation in type 2 diabetic patients

    PubMed Central

    Cabrales, Pedro; Vázquez, Miguel A Salazar; Vázquez, Beatriz Y Salazar; Rodríguez-Morán, Martha; Intaglietta, Marcos; Guerrero-Romero, Fernando

    2008-01-01

    Objective: To test the hypothesis that glycosylation of hemoglobin constitutes a risk factor for hypertension. Methods: A total of 129 relative uniform diabetic subjects (86 women and 42 men) were enrolled in a cross sectional study. Exclusion criteria included alcohol consumption, smoking, ischemic heart disease, stroke, neoplasia, renal, hepatic, and chronic inflammatory disease. Systolic and diastolic pressures were recorded in subsequent days and mean arterial blood pressure (MAP) was determined. Hemoglobin glycosylation was measured by determining the percentage glycosylated hemoglobin (HbA1c) by means of the automated microparticle enzyme immunoassay test. Results: MAP was found to be independent of the concentration of HbA1c; however, correcting MAP for the variability in hematocrit, to evidence the level of vasoconstriction (or vasodilatation) showed that MAP is negatively correlated with the concentration of HbA1c (p for trend <0.05), when patients treated for hypertension are excluded from the analysis. Patients treated for hypertension showed the opposite trend with increasing MAP as HbA1c increased (p for the difference in trends <0.05). Conclusions: Glycosylation per se appears to lead to blood pressure reduction in type 2 diabetic patients untreated for hypertension. Treatment for hypertension may be associated with a level of endothelial dysfunction that interferes with the antihypertensive effect of HbA1c. PMID:19066010

  17. Severe α-thalassemia intermedia due to a compound heterozygosity for the highly unstable Hb Adana (HBA2: c.179G>A) and a novel codon 24 (HBA2: c.75T>A) mutation.

    PubMed

    Megawati, Dewi; Nainggolan, Ita M; Swastika, Maria; Susanah, Susi; Mose, Johanes C; Harahap, Alida R; Setianingsih, Iswari

    2014-01-01

    We report a novel mutation at codon 24 of the α2-globin gene (HBA2: c.75T > A) found in a Sundanese family. This novel mutation was detected during prenatal diagnosis. The couple already had a 7-year-old boy who exhibited clinically severe α-thalassemia intermedia (α-TI), and he was found to be a compound heterozygote for the novel mutation at codon 24 and the previously described Hb Adana (HBA2: c.179G > A) at codon 59 of the α2-globin gene. The father was a carrier of the novel point mutation and showed normal hemoglobin (Hb) and a low mean corpuscular volume (MCV) and mean corpuscular Hb (MCH) value.

  18. Mutations in the paralogous human alpha-globin genes yielding identical hemoglobin variants.

    PubMed

    Moradkhani, Kamran; Préhu, Claude; Old, John; Henderson, Shirley; Balamitsa, Vera; Luo, Hong-Yuan; Poon, Man-Chiu; Chui, David H K; Wajcman, Henri; Patrinos, George P

    2009-06-01

    The human alpha-globin genes are paralogues, sharing a high degree of DNA sequence similarity and producing an identical alpha-globin chain. Over half of the alpha-globin structural variants reported to date are only characterized at the amino acid level. It is likely that a fraction of these variants, with phenotypes differing from one observation to another, may be due to the same mutation but on a different alpha-globin gene. There have been very few previous examples of hemoglobin variants that can be found at both HBA1 and HBA2 genes. Here, we report the results of a systematic multicenter study in a large multiethnic population to identify such variants and to analyze their differences from a functional and evolutionary perspective. We identified 14 different Hb variants resulting from identical mutations on either one of the two human alpha-globin paralogue genes. We also showed that the average percentage of hemoglobin variants due to a HBA2 gene mutation (alpha2) is higher than the percentage of hemoglobin variants due to the same HBA1 gene mutation (alpha1) and that the alpha2/alpha1 ratio varied between variants. These alpha-globin chain variants have most likely occurred via recurrent mutations, gene conversion events, or both. Based on these data, we propose a nomenclature for hemoglobin variants that fall into this category.

  19. A recombinant polymeric hemoglobin with conformational, functional, and physiological characteristics of an in vivo O2 transporter.

    PubMed

    Bobofchak, Kevin M; Mito, Toshiaki; Texel, Sarah J; Bellelli, Andrea; Nemoto, Masaaki; Traystman, Richard J; Koehler, Raymond C; Brinigar, William S; Fronticelli, Clara

    2003-08-01

    With the objective of developing a recombinant oxygen carrier suitable for therapeutic applications, we have employed an Escherichia coli expression system to synthesize in high-yield hemoglobin (Hb) Minotaur, containing alpha-human and beta-bovine chains. Polymerization of Hb Minotaur through S-S intermolecular cross-linking was obtained by introducing a Cys at position beta9 and substituting the naturally occurring Cys. This homogeneous polymer, Hb Polytaur, has a molecular mass of approximately 500 kDa and was resistant toward reducing agents present in blood. In mice, the circulating half-time (3 h) was fivefold greater than adult human Hb (HbA). The half-time of autooxidation measured in blood (46 h) exceeded the circulating retention time. Hypervolemic exchange transfusion resulted in increased arterial blood pressure similar to that with albumin. The increase in pressure was less than that obtained by transfusion of cross-linked tetrameric Hb known to undergo renovascular extravasation. The nitric oxide reactivity of Hb Polytaur was similar to HbA, suggesting that the diminished pressor response to Hb Polytaur was probably related to diminished extravasation. Transfusion of 3% Hb Polytaur during focal cerebral ischemia reduced infarct volume by 22%. Therefore, site-specific Cys insertion on the Hb surface results in uniform size polymers that do not produce the large pressor response seen with tetrameric Hb. Polymerization maintains physiologically relevant oxygen and heme affinity, stability toward denaturation and oxidation, and effective oxygen delivery as indicated by reduced cerebral ischemic damage.

  20. Dietary patterns associated with HbA1c and LDL cholesterol among individuals with type 1 diabetes in China

    PubMed Central

    Jaacks, Lindsay M.; Crandell, Jamie; Mendez, Michelle A.; Lamichhane, Archana P.; Liu, Wei; Ji, Linong; Du, Shufa; Rosamond, Wayne; Popkin, Barry M.; Mayer-Davis, Elizabeth J.

    2015-01-01

    Aims To identify dietary patterns that influence cardiometabolic risk among individuals with type 1 diabetes (T1D) in China. Methods Data are from a cross-sectional study of T1D in China (n=99). Dietary intake was assessed using three 24-hour recalls. Reduced rank regression was used to identify dietary patterns from a set of 20 food groups that maximized the explained variation in glycated hemoglobin A1c (HbA1c) and low-density lipoprotein (LDL) cholesterol. Results Dietary pattern 1 was characterized by low intakes of wheat products and high-fat cakes, and high intakes of beans and pickled vegetables. Dietary pattern 2 was characterized by low intakes of high-fat cakes, nuts/seeds, fish/shellfish, and teas/coffee, and high intakes of rice and eggs. Participants in the highest tertile of dietary pattern 1 had significantly (p<0.05) higher HbA1c and LDL cholesterol compared to participants in the lowest tertile: mean difference in HbA1c was 1.0 percentage point (11mmol/mol) and in LDL cholesterol was 0.36 mmol/L after adjustment for age and household income. Dietary pattern 2 was not associated with HbA1c or LDL cholesterol. Conclusions We identified a dietary pattern that is significantly related to HbA1c and LDL cholesterol. These findings provide support for behavioral strategies to prevent complications in individuals with T1D in China. PMID:25630525

  1. [Clinical and hematological profile of Lepore Hemoglobin in Ivory Coast].

    PubMed

    Sangare, A; Sanogo, I; Meite, M; Segbena, A; Toure, A H; Elenga, J P; Siransy, L; Allangba, O

    1994-01-01

    Out of 97320 hemoglobin electrophoreses performed in Abidjan between January 1976 and January 1991, all subjects with hemoglobin Lepore were isolated. This trait was identified by three techniques, i.e., alkaline pH electrophoresis, acid pH electrophoresis, and isoelectric focusing. Seventy-nine cases of hemoglobin Lepore were observed. All were heterozygotes with type HbA-Lepore (n = 54), HbC-Lepore (n = 8) or HbS Lepore (n = 17). Where heterozygosis A and C had clinically silent, heterozygosis Hb-S Lepore resulted in a moderate chronic hemolytic anemia and, in all cases, painful episodes similar to those observed during homozygote sickle-cell disease. However the onset of episodes was later and their occurrence was less frequent. On hemograms, the Lepore trait (HbA Lepore) appeared as a pseudo-polyglobulia with microcytosis; similar features were observed for heterozygosis HbC Lepore. Heterozygosis HbS Lepore caused moderate anemia (mean hemoglobin level: 10.66 g/dl) and microcytosis (MGV = 68.8 fl). The characteristics show that the clinical and hematological behavior of hemoglobin Lepore, a rare hemoglobin, is similar to heterozygous beta-thalassemia.

  2. 24 CFR 904.303 - Organizing the HBA.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    .... (a) The HBA should be organized and incorporated as early in the life of the development as is feasible, in order to allow selected homebuyers an opportunity to meet each other and begin forging a...

  3. Randomized Controlled Trial of a Community Health Worker Self-Management Support Intervention Among Low-Income Adults With Diabetes, Seattle, Washington, 2010–2014

    PubMed Central

    Taylor, Leslie; Silverman, Julie; Kiefer, Meghan; Hebert, Paul; Lessler, Dan; Krieger, James

    2017-01-01

    Introduction Community health workers (CHWs) can improve diabetes outcomes; however, questions remain about translating research findings into practical low-intensity models for safety-net providers. We tested the effectiveness of a home-based low-intensity CHW intervention for improving health outcomes among low-income adults with diabetes. Methods Low-income patients with glycated hemoglobin A1c (HbA1c) of 8.0% or higher in the 12 months before enrollment from 3 safety-net providers were randomized to a 12-month CHW-delivered diabetes self-management intervention or usual care. CHWs were based at a local health department. The primary outcome was change in HbA1c from baseline enrollment to 12 months; secondary outcomes included blood pressure and lipid levels, quality of life, and health care use. Results The change in HbA1c in the intervention group (n = 145) (unadjusted mean of 9.09% to 8.58%, change of −0.51) compared with the control group (n = 142) (9.04% to 8.71%, change of −0.33) was not significant (P = .54). In an analysis of participants with poor glycemic control (HbA1c >10%), the intervention group had a 1.23-point greater decrease in HbA1c compared with controls (P = .046). For the entire study population, we found a decrease in reported physician visits (P < .001) and no improvement in health-related quality of life (P = .07) in the intervention group compared with the control group. Conclusion A low-intensity CHW-delivered intervention to support diabetes self-management did not significantly improve HbA1c relative to usual care. Among the subgroup of participants with poor glycemic control (HbA1c >10% at baseline), the intervention was effective. PMID:28182863

  4. Socioeconomic status and glycemic control in adult patients with type 2 diabetes: a mediation analysis

    PubMed Central

    Houle, Janie; Lauzier-Jobin, François; Beaulieu, Marie-Dominique; Meunier, Sophie; Coulombe, Simon; Côté, José; Lespérance, François; Chiasson, Jean-Louis; Bherer, Louis; Lambert, Jean

    2016-01-01

    Objective The purpose of this study is to examine the contribution of health behaviors (self-management and coping), quality of care, and individual characteristics (depressive symptoms, self-efficacy, illness representations) as mediators in the relationship between socioeconomic status (SES) and glycemic control. Methods A sample of 295 adult patients with type 2 diabetes was recruited at the end of a diabetes education course. Glycemic control was evaluated through glycosylated hemoglobin (HbA1c). Living in poverty and education level were used as indicators of SES. Results Bootstrapping analysis showed that the significant effects of poverty and education level on HbA1c were mediated by avoidance coping and depressive symptoms. The representation that diabetes is unpredictable significantly mediated the relationship between living in poverty and HbA1c, while healthy diet mediated the relationship between education level and HbA1c. Conclusions To improve glycemic control among patients with low SES, professionals should regularly screen for depression, offering treatment when needed, and pay attention to patients' illness representations and coping strategies for handling stress related to their chronic disease. They should also support patients in improving their self-management skills for a healthy diet. PMID:27239316

  5. The optimal target hemoglobin.

    PubMed

    Ritz, E; Schwenger, V

    2000-07-01

    There is still controversy concerning the optimal target hemoglobin during treatment with recombinant human erythropoietin (rHuEPO). Some evidence suggests that hemoglobin concentrations higher than currently recommended lead to improvements in cognitive function, physical performance, and rehabilitation. At least in patients with advanced cardiac disease, however, one controlled trial failed to show a benefit from normalizing predialysis hemoglobin concentrations. In contrast, preliminary observations in three additional studies (albeit with limited statistical power) failed to show adverse cardiovascular effects from normalization of hemoglobin, but definite benefit with respect to quality of life, physical performance, and cardiac geometry. These observations are consistent with the notion that hemoglobin concentrations higher than those recommended by the National Kidney Foundation Dialysis Outcomes Quality Initiative Anemia Work Group are beneficial, at least in patients without advanced cardiac disease.

  6. Falsely increased HbA1c values by HPLC and falsely decreased values by immunoassay lead to identification of Hb Okayama and help in the management of a diabetic patient.

    PubMed

    Frers, C R; Dorn, S; Schmidt, W; Kochhan, L; Simon-Schultz, J; Arndt, R

    2000-01-01

    A falsely increased HbA1c value of 47.1% was determined by cation exchange chromatography during a routine HbA1c measurement of the blood sample from a 63-year-old diabetic male patient living in Hamburg, Germany. In former determinations by immunological assays falsely decreased values in the range of 5.0 to 5.5% were obtained. The sample was inconspicuous in alkaline hemoglobin electrophoresis. But acid hemoglobin electrophoresis confirmed the falsely increased value. These facts let us consider the existence of a heterozygous "silent hemoglobin variant", such as hemoglobin Okayama, with an amino acid substitution in one of the first four amino acids of the beta chain, representing the epitope of common immunoassays. DNA analyses confirmed this presumption and we found the heterozygous mutation hemoglobin Okayama [beta 2 (NA 2) His (CAC)-->Gln (CAA)]. Knowing that an immunological assay only detects about half of the present HbA1c, the obtained values can be used for therapeutic management of this diabetic patient.

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

    PubMed

    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.

  8. Hemoglobin e syndromes: emerging diagnostic challenge in north India.

    PubMed

    Sharma, Anjali; Marwah, Sadhna; Buxi, Gurdeep; Yadav, Rajbala

    2013-03-01

    Hemoglobin E (HbE) is one of the world's most common and important mutations. HbE disorders may be found in heterozygous (AE), homozygous (EE) and compound heterozygous state. It is important to distinguish HbE disorders diagnostically because of marked differences in clinical course among different genotypes. To find out whether RBC indices as obtained from automated cell counter can provide a clue to the diagnosis of HbE disease. This study was carried out in the Department of Clinical Pathology, PGIMER, Dr. Ram Manohar Lohia Hospital, New Delhi. It included antenatal pregnant females brought for routine check-up as well as referred patients suspected of having hemoglobinopathies. High Performance liquid chromatography was used as a confirmatory test for identification of hemoglobinopathy. Total 20 cases of subtype homozygous HbE (3), HbE trait (12) and Eβ-thalassemia (5) were identified. Statistical analysis was done to find out correlation between levels of HBA2, HBF with RBC indices. (a) There was negative correlation between HbA2/E peak values and RBC indices (Mean corpuscular volume (MCV) and Mean corpuscular hemoglobin) among all the three groups taken together. (b) There was positive correlation between HbA2/E and Red cell distribution width (RDW). (c) There was positive correlation between HbF values with MCV. The finding of positive correlation between HbA2/E and RDW may help in differentiating βthal (RDW normal) from HbE/βthal. In a patient with microcytic hypochromic blood picture and increased RDW, diagnosis of HbE/βthal should also be considered along with the more common Iron deficiency anemia. Thus, new insights into the knowledge of these diseases are important because they impart diagnostic challenges to all the experts involved in the treatment of anemic patients.

  9. A disposable amperometric dual-sensor for the detection of hemoglobin and glycated hemoglobin in a finger prick blood sample.

    PubMed

    Moon, Jong-Min; Kim, Dong-Min; Kim, Moo Hyun; Han, Jin-Yeong; Jung, Dong-Keun; Shim, Yoon-Bo

    2017-05-15

    A disposable microfluidic amperometric dual-sensor was developed for the detection of glycated hemoglobin (HbA1C) and total hemoglobin (Hb), separately, in a finger prick blood sample. The accurate level of total Hb was determined through the measurements of the cathodic currents of total Hb catalyzed by a toluidine blue O (TBO)-modified working electrode. Subsequently, after washing unbound Hb in the fluidic channel of dual sensor with PBS, the cathodic current by only HbA1C captured on aptamer was monitored using another aptamer/TBO-modified working electrode in the channel. To modify the sensor probe, poly(2,2´:5´,5″-terthiophene-3´-p-benzoic acid) and a multi-wall carbon nanotube (MWCNT) composite layer (pTBA@MWCNT) was electropolymerized on a screen printed carbon electrode (SPCE), followed by immobilization of TBO for the total Hb probe and aptamer/TBO for the HbA1C probe, respectively. The characterization of each sensor surface was performed using cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS), X-ray photoelectron spectroscopy (XPS), quartz crystal microbalance (QCM), field-emission scanning electron microscopy (FE-SEM), and transmission electron microscopy (TEM). The experimental conditions affecting the analytical signal were optimized in terms of the amount of TBO, pH, temperature, binding time, applied potential, and the content ratio of monomer and MWCNT. The dynamic ranges of Hb and HbA1C were from 0.1 to 10µM and from 0.006 to 0.74µM, with detection limits of 82(±4.2)nM and 3.7(±0.8)nM, respectively. The reliability of the proposed microfluidic dual-sensor for a finger prick blood sample (1µL) was evaluated in parallel with a conventional method (HPLC) for point-of-care analysis.

  10. Phylogeny of Echinoderm Hemoglobins

    PubMed Central

    Christensen, Ana B.; Herman, Joseph L.; Elphick, Maurice R.; Kober, Kord M.; Janies, Daniel; Linchangco, Gregorio; Semmens, Dean C.; Bailly, Xavier; Vinogradov, Serge N.; Hoogewijs, David

    2015-01-01

    Background Recent genomic information has revealed that neuroglobin and cytoglobin are the two principal lineages of vertebrate hemoglobins, with the latter encompassing the familiar myoglobin and α-globin/β-globin tetramer hemoglobin, and several minor groups. In contrast, very little is known about hemoglobins in echinoderms, a phylum of exclusively marine organisms closely related to vertebrates, beyond the presence of coelomic hemoglobins in sea cucumbers and brittle stars. We identified about 50 hemoglobins in sea urchin, starfish and sea cucumber genomes and transcriptomes, and used Bayesian inference to carry out a molecular phylogenetic analysis of their relationship to vertebrate sequences, specifically, to assess the hypothesis that the neuroglobin and cytoglobin lineages are also present in echinoderms. Results The genome of the sea urchin Strongylocentrotus purpuratus encodes several hemoglobins, including a unique chimeric 14-domain globin, 2 androglobin isoforms and a unique single androglobin domain protein. Other strongylocentrotid genomes appear to have similar repertoires of globin genes. We carried out molecular phylogenetic analyses of 52 hemoglobins identified in sea urchin, brittle star and sea cucumber genomes and transcriptomes, using different multiple sequence alignment methods coupled with Bayesian and maximum likelihood approaches. The results demonstrate that there are two major globin lineages in echinoderms, which are related to the vertebrate neuroglobin and cytoglobin lineages. Furthermore, the brittle star and sea cucumber coelomic hemoglobins appear to have evolved independently from the cytoglobin lineage, similar to the evolution of erythroid oxygen binding globins in cyclostomes and vertebrates. Conclusion The presence of echinoderm globins related to the vertebrate neuroglobin and cytoglobin lineages suggests that the split between neuroglobins and cytoglobins occurred in the deuterostome ancestor shared by echinoderms and

  11. Changes in HbA1c, body weight, and systolic blood pressure in type 2 diabetes patients initiating dapagliflozin therapy: a primary care database study

    PubMed Central

    Scheerer, Markus F; Rist, Roland; Proske, Orm; Meng, Annika; Kostev, Karel

    2016-01-01

    Aims To investigate changes in glycated hemoglobin (HbA1c), body weight (BW), and systolic blood pressure (SBP) in type 2 diabetes (T2D) primary care patients initiating dapagliflozin treatment. Methods T2D patients who started dapagliflozin in 985 general and 32 diabetologist practices (Disease Analyzer, Germany: December 2012–October 2014) were analyzed (3- and 6-month follow-up). Multivariate linear regression analyses were used to identify clinical characteristics and comorbidity associated with changes in HbA1c, BW, and SBP. Results The study included 1,169 T2D patients (age: 62.5 years; men: 59.3%; diabetologist care: 23%) with newly initiated dapagliflozin therapy. At the 3-month stage, dapagliflozin significantly reduced HbA1c (−0.8%±1.4%) compared to the baseline (8.5%±1.5%) (P<0.001). Changes were maintained after 6 months (−0.8%±1.5%) (P<0.001). Patients with high baseline HbA1c values (>9%) showed greater reductions in HbA1c than the overall sample (3 months −1.8%, 6 months −1.8%; both P<0.05). BW and SBP also showed statistically significant reductions with dapagliflozin over 3 and 6 months (−2.2 kg, P<0.001; −2.2 mmHg, P=0.003 and −2.5 kg, P<0.001; −2.3 mmHg, P=0.011, respectively). After 3 months, 53% of patients achieved a reduction in both HbA1c and BW; the same holds true for 45% of patients at the 6-month mark. Similar results were observed both in general and diabetologist practices. In multivariate analyses, baseline HbA1c (parameter estimate: −0.6479) and diabetologist care (−0.2553) were independent predictors of HbA1c change (6 months) (all P<0.05). Conclusion T2D patients treated with dapagliflozin therapy achieved statistically significant reductions in HbA1c, BW, and SBP in a real-world primary and diabetologist care setting. The changes were comparable to the results of the dapagliflozin clinical trial program. PMID:27822077

  12. Interpreting Hemoglobin A1C in Combination With Conventional Risk Factors for Prediction of Cardiovascular Risk

    PubMed Central

    Jarmul, Jamie A.; Pignone, Michael; Pletcher, Mark J.

    2015-01-01

    Background Hemoglobin A1C (HbA1C) is associated with increased risk of cardiovascular events, but its use for prediction of cardiovascular disease (CVD) events in combination with conventional risk factors has not been well defined. Methods and Results To understand the effect of HbA1C on CVD risk in the context of other CVD risk factors, we analyzed HbA1C and other CVD risk factor measurements in 2000 individuals aged 40-79 years old without pre-existing diabetes or cardiovascular disease from the 2011-2012 NHANES survey. The resulting regression model was used to predict the HbA1C distribution based on individual patient characteristics. We then calculated post-test 10-year atherosclerotic cardiovascular disease (ASCVD) risk incorporating the actual versus predicted HbA1C, according to established methods, for a set of example scenarios. Age, gender, race/ethnicity and traditional cardiovascular risk factors were significant predictors of HbA1C in our model, with the expected HbA1C distribution being significantly higher in non-Hispanic black, non-Hispanic Asian and Hispanic individuals than non-Hispanic white/other individuals. Incorporating the expected HbA1C distribution into pretest ASCVD risk has a modest effect on post-test ASCVD risk. In the patient examples we assessed, having an HbA1C < 5.7% reduced post-test risk by 0.4%-2.0% points, whereas having an HbA1C ≥ 6.5% increased post-test risk by 1.0%-2.5% points, depending on the scenario. The post-test risk increase from having an HbA1C ≥ 6.5 % tends to approximate the risk increase from being five years older in age. Conclusions HbA1C has modest effects on predicted ASCVD risk when considered in the context of conventional risk factors. PMID:26349840

  13. The amino-acid sequence of alpha A- and beta-chains from the major hemoglobin component of American flamingo (Phoenicopterus ruber ruber).

    PubMed

    Godovac-Zimmermann, J; Braunitzer, G

    1984-04-01

    The complete amino-acid sequence of alpha A- and beta-chains from the major hemoglobin component (HbA) of American Flamingo ( Phoenicopterus ruber ruber) is presented. The minor component (HbD) with alpha D-chains was detected in similar amounts (25%) as in chicken and pheasant hemoglobins. The comparison of American Flamingo and Greylag Goose (Anser anser) hemoglobins shows that alpha A-chains differ by 22 exchanges and beta-chains by only 4 exchanges. Two substitutions modify alpha 1 beta 1-contacts. Amino-acid replacements between American Flamingo and other bird hemoglobins are discussed.

  14. Hemoglobin Villejuif [beta 123(H1) Thr----Ile]: a new variant found in coincidence with polycythemia vera.

    PubMed

    Wajcman, H; Mrad, A; Blouquit, Y; Parmentier, C; Riou, J; Galacteros, F

    1989-12-01

    A new abnormal hemoglobin, Hb Villejuif [beta 123(H1) Thr----Ile] has been discovered during the exploration of a polycythemia in a 87-year-old patient of French origin. The isoelectric focusing of the lysate revealed the presence of a variant hemoglobin with an isoelectric point very close to that of HbA. The oxygen binding properties of the patient's red blood cells being normal, it was clear that the polycythemia was not a consequence of the presence of this hemoglobin. In fact, the red blood cell morphology and the involvement of the other blood cell lines, demonstrating excessive hemopoiesis, led to the diagnosis of polycythemia vera.

  15. Elevated glycated hemoglobin predicts macrosomia among Asian Indian pregnant women (WINGS-9)

    PubMed Central

    Bhavadharini, Balaji; Mahalakshmi, Manni Mohanraj; Deepa, Mohan; Harish, Ranjani; Malanda, Belma; Kayal, Arivudainambi; Belton, Anne; Saravanan, Ponnusamy; Ranjit, Unnikrishnan; Uma, Ram; Anjana, Ranjit Mohan; Mohan, Viswanathan

    2017-01-01

    Aim: The aim of this study was to determine the optimal glycated hemoglobin (HbA1c) cut point for diagnosis of gestational diabetes mellitus (GDM) and to evaluate the usefulness of HbA1c as a prognostic indicator for adverse pregnancy outcomes. Methods: HbA1c estimations were carried out in 1459 pregnant women attending antenatal care centers in urban and rural Tamil Nadu in South India. An oral glucose tolerance test was carried out using 75 g anhydrous glucose, and GDM was diagnosed using the International Association of the Diabetes and Pregnancy Study Groups criteria. Results: GDM was diagnosed in 195 women. Receiver operating curves showed a HbA1c cut point of ≥ 5.0% (≥31 mmol/mol) have a sensitivity of 66.2% and specificity of 56.2% for identifying GDM (area under the curve 0.679, confidence interval [CI]: 0.655–0.703). Women with HbA1c ≥ 5.0% (≥31 mmol/mol) were significantly older and had higher body mass index, greater history of previous GDM, and a higher prevalence of macrosomia compared to women with HbA1c < 5.0% (<31 mmol/mol). The adjusted odds ratio for macrosomia in those with HbA1c ≥ 5.0% (≥31 mmol/mol) was 1.92 (CI: 1.24–2.97, P = 0.003). However, other pregnancy outcomes were not significantly different. Conclusion: In Asian Indian pregnant women, a HbA1c of 5.0% (31 mmol/mol) or greater is associated with increased risk of macrosomia. PMID:28217520

  16. The value of admission glycosylated hemoglobin level in patients with acute myocardial infarction

    PubMed Central

    Cakmak, Mahmut; Cakmak, Nazmiye; Cetemen, Sebnem; Tanriverdi, Halil; Enc, Yavuz; Teskin, Onder; Kilic, I Dogu

    2008-01-01

    BACKGROUND: Glycosylated hemoglobin (HbA1c) level on admission is a prognostic factor for mortality in patients with and without diabetes after myocardial infarction. In the present study, the authors examined the relationship between admission HbA1c level and myocardial perfusion abnormalities in patients with acute myocardial infarction. METHODS: One hundred consecutive patients with acute myocardial infarction who were treated with thrombolytic therapy were included in the present prospective study. Blood glucose and HbA1c levels of all patients were measured within 3 h of admission. Patients were divided into three groups according to HbA1c level: 4.5% to 6.4% (n=25), 6.5% to 8.5% (n=28) and higher than 8.5% (n=47). All patients then underwent exercise thallium-201 imaging and coronary angiography to determine ischemic scores and the number of diseased coronary arteries four weeks after admission. RESULTS: Seven patients died within the four-week follow-up period. There was a significant relationship between admission HbA1c level and mortality (P=0.009). Furthermore, there was a significant relationship between HbA1c level and total ischemic scores in patients with acute myocardial infarction (r=0.482; P=0.001). Ischemic scores increased as HbA1c levels increased in patients with acute myocardial infarction. CONCLUSIONS: The results demonstrated that admission plasma glucose and HbA1c levels are prognostic factors associated with mortality after acute myocardial infarction. PMID:18464942

  17. Higher sensitivity of capillary electrophoresis in detecting hemoglobin A2'compared to traditional gel electrophoresis.

    PubMed

    Oleske, Deanna Alicia; Huang, Richard Sheng Poe; Dasgupta, Amitava; Nguyen, Andy; Wahed, Amer

    2014-01-01

    HbA2' (also called Hb B2) is the most common delta-globin chain defect and is reported to occur in 1-2% of the African American population. The major clinical significance of HbA2' is that the failure to detect it might lead to an underestimation of the total HbA2, leading to failure to diagnose β-thalassemia minor. In order to diagnose β-thalassemia minor, both HbA2 and HbA2' levels must be combined.Hb A2' accounts for a small percentage (1-2%) of the total hemoglobin in heterozygotes. It is difficult to detect this small amount by traditional gel electrophoresis. Using HPLC Hb A2' is easily detected as it produces a minor peak in the S window. Other conditions which might interfere with detection of HbA2' by HPLC include Hb S trait or Hb SS disease (Hb A2' hidden in the S peak), transfused Hb SS (Hb S peak may be very small), Hb C trait or Hb CC disease (glycosylated Hb C elutes in the S window), and Hb G (Hb G2 elutes in the S window). All of the above conditions, including Hb A2', occur most commonly in the same ethnic group (African American). We reviewed 654 consecutive cases over a period of three months for the presence of Hb A2' in our laboratory where capillary electrophoresis is used as the primary diagnostic tool. We detected seven cases (1.07 %) of HbA2'. In contrast, we did not detect any HbA2' using conventional gel electrophoresis in the last one year (2,580 cases). Although in none of the seven cases the sum of Hb A2 and Hb A2' exceeded 3.5%, we believe that capillary electrophoresis allows for a better detection of Hb A2' than gel electrophoresis and HPLC.

  18. 24 CFR 904.304 - Functions of the HBA.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ...) Coordinating, supervising, or managing the operation of credit union, child care, or other supportive services...) Developing programs and contracting for services such as child care centers to be located in the community... organizations; (5) Assisting homebuyers in planning the management role of the HBA and in negotiating...

  19. [Rapid hemoglobin A1c determination (a new possibility in diabetes care)].

    PubMed

    Jermendy, G; Nádas, J; Farkas, K

    1999-05-30

    To assess the long-term metabolic control, immunochemical method was used for hemoglobin A1c (HbA1c) determinations in diabetic patients. The use of DCA 2000 device (Bayer) resulted in immediate (< 6 min) HbA1c values. The reproducibility of this method was acceptable (within-run coefficients of variations were 3.48% and 4.80%). A close, linear correlation (r = 0.974; p < 0.001; n = 106) between HbA1c-values measured simultaneously by DCA 2000 and DIAMAT (Bio-Rad, method: high pressure liquid chromatography) was observed in diabetic patients. The new immunochemical method proved to be simple and reliable. The immediate (within 6 min) result makes the therapeutic decision easier during the care of diabetic patients.

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

    SciTech Connect

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

    2005-01-01

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

  1. Boronate-Modified Interdigitated Electrode Array for Selective Impedance-Based Sensing of Glycated Hemoglobin.

    PubMed

    Boonyasit, Yuwadee; Laiwattanapaisal, Wanida; Chailapakul, Orawon; Emnéus, Jenny; Heiskanen, Arto R

    2016-10-04

    An impedance-based label-free affinity sensor was developed for the recognition of glycated hemoglobin (HbA1c). Interdigitated gold microelectrode arrays (IDAs) were first modified with a self-assembled monolayer of cysteamine followed by cross-linking with glutaraldehyde and subsequent binding of 3-aminophenylboronic acid (APBA), which selectively binds HbA1c via cis-diol interactions. Impedance sensing was demonstrated to be highly responsive to the clinically relevant HbA1c levels (0.1%-8.36%) with a detection and quantitation limit of 0.024% (3σ/slope) and 0.08% (10σ/slope), respectively. The specificity of the assay was evaluated with nonglycated hemoglobin (HbAo), showing that the impedance response remained unchanged over the concentration range of 10 to 20 g dL(-1) HbAo. This demonstrated that the sensor system could be used to specifically distinguish HbA1c from HbAo. Moreover, the binding of HbA1c to the APBA-modified electrodes was reversible, providing a reusable sensing interface as well as showing a stable response after 4 weeks (96% of the initial response). When assaying normal (4.10%) and diabetic (8.36%) HbA1c levels (10 assays per day during a three-day period including a regeneration step after each assay), the overall assay reproducibility, expressed as relative standard error of the mean (n = 30), was 1.1%. The performance of the sensor system was also compared with a commercial method (n = 15) using patient-derived blood samples. A good agreement (Bland-Altman bias plot) and correlation (Passing-Bablok regression analysis) was demonstrated between the boronate-based affinity sensor and the standard method.

  2. Changes in the conformational state of hemoglobin in hemodialysed patients with chronic renal failure.

    PubMed

    Pieniazek, Anna; Gwozdzinski, Krzysztof

    2015-01-01

    The aim of this study was to evaluate the properties of internal components of erythrocytes in chronic renal failure (CRF) patients undergoing hemodialysis (HD) in comparison to control subjects. For investigation of conformational state of hemoglobin and nonheme proteins (NHP) the maleimide spin label (MSL) in electron paramagnetic resonance (EPR) was applied. The studies were performed using MSL in whole cells and hemolysate as well as proteins separated by ion exchange chromatography and checked by electrophoresis. Additionally the level of -SH groups in hemolysate and isolated internal proteins of CRF erythrocytes was determined using 4,4'-dithiodipyridine. All measurements were performed before and after hemodialysis. Oxidative stress accompanying CRF/hemodialysed patients caused a significant decrease in the mobility of internal components inside erythrocytes indicated by MSL (P < 0.02). The significant decrease in mobility of spin labeled HbA1c and HbA both before and after HD (P < 0.0002) as well as in nonheme proteins before hemodialysis (P < 0.05) versus control was indicated. Decrease in mobility of internal components of erythrocytes was accompanied by loss of thiols before and after hemodialysis versus control in NHP (P < 0.05), HbA1c (P < 0.0002), and HbA (P < 0.0005). These findings showed oxidative influence of hemodialysis on hemoglobins and internal nonheme proteins in erythrocytes of CRF patients.

  3. Autofluorescence characterization of advanced glycation end products of hemoglobin

    NASA Astrophysics Data System (ADS)

    Vigneshwaran, Nadanathangam; Bijukumar, Gopalakrishnapillai; Karmakar, Nivedita; Anand, Sneh; Misra, Anoop

    2005-01-01

    This article describes the analysis of autofluorescence of advanced glycation end products of hemoglobin (Hb-AGE). Formed as a result of slow, spontaneous and non-enzymatic glycation reactions, Hb-AGE possesses a characteristic autofluorescence at 308/345 nm ( λex/ λem). Even in the presence of heme as a quenching molecule, the surface presence of the glycated adduct gave rise to autofluorescence with the quantum yield of 0.19. The specificity of monoclonal antibody developed against common AGE structure with Hb-AGE was demonstrated using reduction in fluorescence polarization value due to increased molecular volume while binding. The formation of fluorescent adduct in hemoglobin in the advanced stage of glycation and the non-fluorescent HbA 1c will be of major use in distinguishing and to know the past status of diabetes mellitus. While autofluorescence correlated highly with HbA 1c value under in vivo condition ( r=0.85), it was moderate in the clinical samples ( r=0.55). The results suggest a non-linear relation between glycemia and glycation, indicating the application of Hb-AGE as a measure of susceptibility to glycation rather than glycation itself.

  4. Rice (Oryza) hemoglobins

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Hemoglobins (Hbs) corresponding to non-symbiotic (nsHb) and truncated (tHb) Hbs have been identified in rice (Oryza). This review discusses the major findings from the current studies on rice Hbs. At the molecular level, a family of the nshb genes, consisting of hb1, hb2, hb3, hb4 and hb5, and a sin...

  5. Gold nanoparticles-coated magnetic microspheres as affinity matrix for detection of hemoglobin A1c in blood by microfluidic immunoassay.

    PubMed

    Chen, Shao-Peng; Yu, Xiao-Dong; Xu, Jing-Juan; Chen, Hong-Yuan

    2011-08-15

    A novel microfluidic immunoassay system for specific detection of hemoglobin A1c (HbA1c) was developed based on a three-component shell/shell/core structured magnetic nanocomposite Au/chitosan/Fe(3)O(4), which was synthesized with easy handling feature of Fe(3)O(4) by magnet, high affinity for gold nanoparticles of chitosan and good immobilization ability for anti-human hemoglobin-A1c antibody (HbA1c mAb) of assembled colloidal gold nanoparticles. The resulting HbA1c mAb/Au/chitosan/Fe(3)O(4) magnetic nanoparticles were then introduced into microfluidic devices coupled with a gold nanoband microelectrode as electrochemical detector. After that, three-step rapid immunoreactions were carried out in the sequence of HbA1c, anti-human hemoglobin antibodies (Hb mAb) and the secondary alkaline phosphatase (AP)-conjugated antibody within 20 min. The current response of 1-naphtol obtained from the reaction between the secondary AP-conjugated antibody and 1-naphthyl phosphate (1-NP) increased proportionally to the HbA1c concentration. Under optimized electrophoresis and detection conditions, HbA1c responded linearly in the concentration of 0.05-1.5 μg mL(-1), with the detection limit of 0.025 μg mL(-1). This system was successfully employed for detection of HbA1c in blood with good accuracy and renewable ability. The proposed method proved its potential use in clinical immunoassay of HbA1c.

  6. Effect of ethnicity on HbA1c levels in individuals without diabetes: Systematic review and meta-analysis

    PubMed Central

    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 <0.001; I2 = 90%, p <0.001], Asians [0.24% (2.6 mmol/mol); 95% CI 0.16 to 0.33 (1.7 to 3.6), p <0.001; I2 = 80%, p = 0.0006] and Latinos [0.08% (0.9 mmol/mol); IC 95% 0.06 to 0.10 (0.7 to 1.1); p <0.001; I2 = 0%; p = 0.72] when compared to Whites. Conclusions/Interpretation This meta-analysis shows that, in individuals without DM, 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

  7. Methylglyoxal modification enhances the stability of hemoglobin and lowers its iron-mediated oxidation reactions: An in vitro study.

    PubMed

    Banerjee, Sauradipta; Chakraborti, Abhay Sankar

    2017-02-01

    Post-translational modification of proteins by Maillard reaction, known as glycation, is thought to be the root cause of different complications, particularly in diabetes mellitus and age-related disorders. Methylglyoxal (MG), a reactive α-oxoaldehyde, increases in diabetic condition and reacts with proteins to form advanced glycation end products (AGEs) following Maillard-like reaction. In the present study, we have investigated the in vitro effect of methylglyoxal (200, 300μm) on the heme protein hemoglobin (HbA0) (100μm) after incubation for one week at 25°C. Compared to HbA0, MG-treated HbA0 exhibited decreased absorbance around 280nm, reduced intrinsic fluorescence and lower surface hydrophobicity. MG treatment was not found to significantly affect the secondary structure of HbA0. The stability of MG-treated HbA0 was found to be higher compared to HbA0. Moreover, H2O2-mediated iron release and subsequent iron-mediated oxidation (Fenton) reactions were found to be lower in presence of MG-treated HbA0 compared to HbA0. As shown by mass spectrometric studies, MG modified Arg-92α, Arg-104β, Arg-31α and Arg-40β of HbA0 to hydroimidazolone adducts. The modifications thus appear to be associated with the observed structural alterations of the heme protein. Considering the increased level of MG in diabetes mellitus as well as its high reactivity, AGEs might be associated with structural and functional modifications of the protein including physiological significance.

  8. Determinants of Glycated Hemoglobin in Subjects With Impaired Glucose Tolerance: Subanalysis of the Japan Diabetes Prevention Program

    PubMed Central

    Sakane, Naoki; Sato, Juichi; Tsushita, Kazuyo; Tsujii, Satoru; Kotani, Kazuhiko; Tominaga, Makoto; Kawazu, Shoji; Sato, Yuzo; Usui, Takeshi; Kamae, Isao; Yoshida, Toshihide; Kiyohara, Yutaka; Sato, Shigeaki; Tsuzaki, Kokoro; Nirengi, Shinsuke; Takahashi, Kaoru; Kuzuya, Hideshi; Group, JDPP Research

    2017-01-01

    Background Limited evidence is available about the relationship of lifestyle factors with glycated hemoglobin (HbA1c) in subjects with impaired glucose tolerance. The aim of study was to identify such determinant factors of HbA1c in subjects with impaired glucose tolerance. Methods This cross-sectional study included 121 men and 124 women with impaired glucose tolerance, who were diagnosed based on a 75-g oral glucose tolerance test. Demographic and biochemical parameters, including the body mass index (BMI), fasting plasma glucose (FPG), 2-h post-load glucose (2-h PG), and HbA1c, were measured. The pancreatic β-cell function and insulin resistance were assessed using homeostasis model assessment (HOMA-β). Dietary intake was assessed by a food frequency questionnaire. Results The levels of FPG, 2-h PG, and carbohydrate intake were correlated with the HbA1c level in men, while the FPG and 2-h PG levels were correlated with the HbA1c level in women. In multiple regression analyses, BMI, FPG, 2-h PG, and white rice intake were associated with HbA1c levels in men, while BMI, FPG, HOMA-β, and bread intake were associated with HbA1c levels in women. Conclusions The present findings suggest that a substantial portion of HbA1c may be composed of not only glycemic but also several lifestyle factors in men with impaired glucose tolerance. These factors can be taken into consideration as modifiable determinants in assessing the HbA1c level for the diagnosis and therapeutic monitoring of the disease course. PMID:28270897

  9. Structural and functional characterization of Delphinus delphis hemoglobin system.

    PubMed

    Manconi, Barbara; Messana, Irene; Maggiani, Federica; Olianas, Alessandra; Pellegrini, Mariagiuseppina; Crnjar, Roberto; Castagnola, Massimo; Giardina, Bruno; Sanna, Maria Teresa

    2009-11-01

    Structural analysis of the hemoglobin (Hb) system of Delphinus delphis revealed a high globin multiplicity: HPLC-electrospray ionization-mass spectrometry (ESI-MS) analysis evidenced three major beta (beta1 16,022 Da, beta2 16,036 Da, beta3 16,036 Da, labeled according to their progressive elution times) and two major alpha globins (alpha1 15,345 Da, alpha2 15,329 Da). ESI-tandem mass and nucleotide sequence analyses showed that beta2 globin differs from beta1 for the substitution Val126 --> Leu, while beta3 globin differs from beta2 for the isobaric substitution Lys65 --> Gln. The alpha2 globin differs from the alpha1 for the substitution Ser15 --> Ala. Anion-exchange chromatography allowed the separation of two Hb fractions and HPLC-ESI-MS analysis revealed that the fraction with higher pI (HbI) contained beta1, beta2 and both the alpha globins, and the fraction with lower pI (HbII) contained beta3 and both the alpha globins. Both D. delphis Hb fractions displayed a lower intrinsic oxygen affinity, a decreased effect of 2,3-BPG and a reduced cooperativity with respect to human HbA(0), with HbII showing the more pronounced differences. With respect to HbA(0), either the substitution Probeta5 --> Gly or the Probeta5 --> Ala is present in all the cetacean beta globins sequenced so far, and it has been hypothesized that position 5 of beta globins may have a role in the interaction with 2,3-BPG. Regarding the particularly lowered cooperativity of HbII, it is interesting to observe that the variant human HbA, characterized by the substitution Lysbeta65 --> Gln (HbJ-Cairo) has a decreased cooperativity with respect to HbA(0).

  10. Hemoglobin A1c and Self-Monitored Average Glucose

    PubMed Central

    Kovatchev, Boris P.; Breton, Marc D.

    2015-01-01

    Background: Previously we have introduced the eA1c—a new approach to real-time tracking of average glycemia and estimation of HbA1c from infrequent self-monitoring (SMBG) data, which was developed and tested in type 2 diabetes. We now test eA1c in type 1 diabetes and assess its relationship to the hemoglobin glycation index (HGI)—an established predictor of complications and treatment effect. Methods: Reanalysis of previously published 12-month data from 120 patients with type 1 diabetes, age 39.15 (14.35) years, 51/69 males/females, baseline HbA1c = 7.99% (1.48), duration of diabetes 20.28 (12.92) years, number SMBG/day = 4.69 (1.84). Surrogate fasting BG and 7-point daily profiles were derived from these unstructured SMBG data and the previously reported eA1c method was applied without any changes. Following the literature, we calculated HGI = HbA1c – (0.009 × Fasting BG + 6.8). Results: The correlation of eA1c with reference HbA1c was r = .75, and its deviation from reference was MARD = 7.98%; 95% of all eA1c values fell within ±20% from reference. The HGI was well approximated by a linear combination of the eA1c calibration factors: HGI = 0.007552*θ1 + 0.007645*θ2 – 3.154 (P < .0001); 73% of low versus moderate-high HGIs were correctly classified by the same factors as well. Conclusions: The eA1c procedure developed in type 2 diabetes to track in real-time changes in average glycemia and present the results in HbA1c-equivalent units has shown similar performance in type 1 diabetes. The eA1c calibration factors are highly predictive of the HGI, thereby explaining partially the biological variation causing discrepancies between HbA1c and its linear estimates from SMBG data. PMID:26553023

  11. Whole Blood Donation Affects the Interpretation of Hemoglobin A1c

    PubMed Central

    Lenters-Westra, Erna; de Kort, Wim; Bokhorst, Arlinke G.; Bilo, Henk J. G.; Slingerland, Robbert J.; Vos, Michel J.

    2017-01-01

    Introduction Several factors, including changed dynamics of erythrocyte formation and degradation, can influence the degree of hemoglobin A1c (HbA1c) formation thereby affecting its use in monitoring diabetes. This study determines the influence of whole blood donation on HbA1c in both non-diabetic blood donors and blood donors with type 2 diabetes. Methods In this observational study, 23 non-diabetic blood donors and 21 blood donors with type 2 diabetes donated 475 mL whole blood and were followed prospectively for nine weeks. Each week blood samples were collected and analyzed for changes in HbA1c using three secondary reference measurement procedures. Results Twelve non-diabetic blood donors (52.2%) and 10 (58.8%) blood donors with type 2 diabetes had a significant reduction in HbA1c following blood donation (reduction >-4.28%, P < 0.05). All non-diabetic blood donors with a normal ferritin concentration predonation had a significant reduction in HbA1c. In the non-diabetic group the maximum reduction was -11.9%, in the type 2 diabetes group -12.0%. When eligible to donate again, 52.2% of the non-diabetic blood donors and 41.2% of the blood donors with type 2 diabetes had HbA1c concentrations significantly lower compared to their predonation concentration (reduction >-4.28%, P < 0.05). Conclusion Patients with type 2 diabetes contributing to whole blood donation programs can be at risk of falsely lowered HbA1c. This could lead to a wrong interpretation of their glycemic control by their general practitioner or internist. PMID:28118412

  12. Correlation Between Glycated Hemoglobin and Homa Indices in Type 2 Diabetes Mellitus: Prediction of Beta-Cell Function from Glycated Hemoglobin

    PubMed Central

    Al-Hakeim, Hussein Kadhem; Abdulzahra, Mohammed Saied

    2015-01-01

    Summary Background The present study aimed to determine the most efficient insulin resistance function related to glycemic control expressed as glycated hemoglobin (HbA1c) in type 2 diabetes mellitus patients (T2DM). The other aim is to derive equations for the prediction of beta cell functions containing HbA1c as a parameter in addition to fasting glucose and insulin. Methods T2DM Patients were grouped according to the following: (1) degree of control (good, fair, and poor control) and (2) insulin resistance as observed in obtained data and significant differences revealed by the homeostasis model assessment (HOMA) of related parameters (insulin resistance = HOMA2IR, beta-cell function = HOMA%B, and insulin sensitivity = HOMA%S) among groups. Correlations and forecasting regression analysis were calculated. Results HbA1c was found to be correlated with insulin resistance parameters in T2DM subgroups. This correlation was also significantly correlated with HOMA%B and the quantitative insulin sensitivity check index (QUICKI) in fair and poor control groups. Regression analysis was used to predict the forecasting equations for HOMA%B. The best applicable equations were derived for healthy control (HOMA2%B=−1.76*FBG+5.00*Insulin+4.69*HbA1c+189.84) and poor control groups (HOMA2%B=0.001* FBG+0.5*Insulin-8.67*HbA1c+101.96). These equations could be used to predict β-cell function (HOMA%B) after FBG, insulin and HbA1c values were obtained for healthy and poor control groups. In the good and fair control groups, the applicability of the HOMA model fails to yield appropriate results. Conclusions Beta-cell function is correlated with QUICKI and HbA1c and could be predicted properly from HbA1c, insulin, and glucose in the healthy and poor control groups. New regression equations were established that involve HbA1c. PMID:28356831

  13. An integrated microfluidic system for measurement of glycated hemoglobin levels by using an aptamer-antibody assay on magnetic beads.

    PubMed

    Chang, Ko-Wei; Li, Jinglun; Yang, Ching-Hsuan; Shiesh, Shu-Chu; Lee, Gwo-Bin

    2015-06-15

    Blood glycated hemoglobin (HbA1c), reflecting the average blood glucose level in the proceeding 2-3 months, is recommended for screening/diagnosing and patient management of diabetes. However, accurate measurement of the HbA1c level at the point of care is hampered by costly, large-scale instruments (such as high-performance liquid chromatography) or reagent instability of classical immunologic methods, which involve antibody-based immunoturbidimetry. In this work, an integrated microfluidic system using aptamer-based testing to measure HbA1c in blood samples is therefore presented. This measuring system used nucleic-acid aptamers that exhibited high sensitivity and high specificity for hemoglobin and HbA1c to perform a stable and robust testing. The compact microfluidic system consumed less samples and reagents and significantly shortened the detection time. Combining the advantages of microfluidics and aptamers, this integrated microsystem presents a promising tool for accurate and point-of-case HbA1c detection. To demonstrate its clinical utility, whole blood samples with clinically-relevant concentrations of HbA1c and Hb were automatically measured on the integrated microfluidic system. Experimental data showed that the developed aptamer-based microfluidic system is capable of detecting HbA1c and Hb with a good linear response. The entire process was completed within 25 min. The aptamer-antibody on-chip sandwich immunoassay may be further refined to allow diabetes screening and diagnosis at lower cost and earlier phase to minimize the risk of diabetic complications.

  14. Use of fructosyl peptide oxidase for HbA1c assay.

    PubMed

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

    2015-03-01

    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.

  15. Vitamin D Deficiency and Its Determinants in Adults: A Sample from Community-Based Settings in the United Arab Emirates

    PubMed Central

    Eldeirawi, Kamal; Harfil, Sondos; Fakhry, Randa

    2017-01-01

    Background. Vitamin D deficiency (VDD) is a public health concern in adults worldwide. This study aims to explore the extent of VDD and its associated factors among adults in the United Arab Emirates (UAE). Subjects and Methods. Quantitative, cross-sectional research was used to assess VDD and its associated factors in 216 adults recruited from randomly selected community-based healthcare settings over a six-month period. Recent values of vitamin D and glycated hemoglobin (HbA1c) were abstracted from medical records, followed by interviews with participants to obtain information on factors related to VDD and other covariates and to measure their heights and weights. Results. A total of 74% of participants demonstrated VDD (vitamin D serum level ≤ 30 nmol/L). Emirati participants had higher odds of having VDD compared to non-Emiratis (OR: 2.95; 95% CI: 1.58–5.52), with also significantly increased odds of the condition appearing in older, less educated, and employed adults. Diabetes type 2 (HbA1c ≥ 6.5%), depression, and obesity were significantly associated with an increased likelihood of VDD after accounting for other covariates. Conclusion. VDD is a significant problem for UAE adults and requires attention by public health policy makers. Diabetes, obesity, and depression need to be considered when screening for vitamin D. PMID:28352281

  16. Interaction between hypericin and hemoglobin.

    PubMed

    Vardapetyan, H R; Martirosyan, A S; Tiratsuyan, S G; Hovhannisyan, A A

    2010-10-05

    In the present work the hypericin interaction with hemoglobin was studied by absorption and fluorescence spectroscopy both under incubation in dark and visible light exposure. An absorption reduction in Soret band of hemoglobin (407 nm) was revealed under the photodynamic influence and incubation in dark with hypericin that had hypericin concentration and time dependent manner. Hypericin reduced the intensity of the hemoglobin emission peaks at 334 and 421 nm, correlating with hypericin concentration, incubation and irradiation time. An obvious increase in electrophoretic mobility of hemoglobin was observed under the incubation with hypericin. Simultaneously, a partial conversion of hemoglobin to met-hemoglobin and a pH decrease in hemoglobin solution were detected. Structural changes of hemoglobin caused by hypericin were accompanied by a change in peroxidase activity of the protein. Thus under the hypericin influence hemoglobin properties as a hydrogen peroxide detector could be improved and an effective determination of peroxide formation could be achieved. This makes hemoglobin an attractive 'recognition' element for construction of third-generation biosensors.

  17. Hemoglobin Drift after Cardiac Surgery

    PubMed Central

    George, Timothy J.; Beaty, Claude A.; Kilic, Arman; Haggerty, Kara A.; Frank, Steven M.; Savage, William J.; Whitman, Glenn J.

    2013-01-01

    Introduction Recent literature suggests that a restrictive approach to red blood cell transfusions is associated with improved outcomes in cardiac surgery (CS) patients. Even in the absence of bleeding, intravascular fluid shifts cause hemoglobin levels to drift postoperatively, possibly confounding the decision to transfuse. We undertook this study to define the natural progression of hemoglobin levels in postoperative CS patients. Methods We included all CS patients from 10/10-03/11 who did not receive a postoperative transfusion. Primary stratification was by intraoperative transfusion status. Change in hemoglobin was evaluated relative to the initial postoperative hemoglobin. Maximal drift was defined as the maximum minus the minimum hemoglobin for a given hospitalization. Final drift was defined as the difference between initial and discharge hemoglobin. Results Our final cohort included 199 patients, 71(36%) received an intraoperative transfusion while 128(64%) did not. The average initial and final hemoglobin for all patients were 11.0±1.4g/dL and 9.9±1.3g/dL, respectively, an final drift of 1.1±1.4g/dL. The maximal drift was 1.8±1.1g/dL and was similar regardless of intraoperative transfusion status(p=0.9). Although all patients’ hemoglobin initially dropped, 79% of patients reached a nadir and experienced a mean recovery of 0.7±0.7g/dL by discharge. On multivariable analysis, increasing CPB time was significantly associated with total hemoglobin drift(Coefficient/hour: 0.3[0.1–0.5]g/dL, p=0.02). Conclusions In this first report of hemoglobin drift following CS, although all postoperative patients experienced downward hemoglobin drift, 79% of patients exhibited hemoglobin recovery prior to discharge. Physicians should consider the eventual upward hemoglobin drift prior to administering red cell transfusions. PMID:22609121

  18. A micro-potentiometric hemoglobin immunosensor based on electropolymerized polypyrrole-gold nanoparticles composite.

    PubMed

    Qu, Lan; Xia, Shanhong; Bian, Chao; Sun, Jizhou; Han, Jinghong

    2009-08-15

    We report a novel micro-potentiometric hemoglobin (Hb) immunosensor based on electrochemically synthesized polypyrrole (PPy)-gold nanoparticles (AuNPs) composite. PPy-AuNPs film with AuNPs uniformly distributed in it was deposited on gold electrode surface by a simple and direct procedure, without the addition of any nanoparticles or reducing agent. And this generic method makes it possible to deposite different polymers on miniaturized electrodes. With the existence of AuNPs, the antibody immobilization onto the electrode surface was facilitated. Morphology study by field emission scanning electron microscope (FE-SEM) confirms the presence of AuNPs in PPy. Based on an ion-sensitive field-effect transistors (ISFETs) integrated chip, a micro-potentiometric immunosensor for Hb and hemoglobin-A1c (HbA1c) has been constructed. The sensor response was linear over the concentration range 60-180 microg/ml Hb and 4-18 microg/ml HbA1c. The Hb concentration in whole blood samples has also been analysed, with a linear dose-response behavior between 125 and 197 microg/ml and a sensitivity of 0.20 mV microg(-1)ml. The measuring ranges of the developed Hb and HbA1c immunosensors meet the clinical demand for measuring the HbA1c/Hb ratio of 5-20%. This sensor results in simple and rapid differential measurement of Hb and HbA1c, and has great potential to become an inexpensive and portable device for monitoring of diabetes.

  19. Hemoglobin: a gas transport molecule that is hormonally regulated in the ovarian follicle in mice and humans.

    PubMed

    Brown, Hannah M; Anastasi, Marie R; Frank, Laura A; Kind, Karen L; Richani, Dulama; Robker, Rebecca L; Russell, Darryl L; Gilchrist, Robert B; Thompson, Jeremy G

    2015-01-01

    An increasing number of nonerythroid tissues are found to express hemoglobin mRNA and protein. Hemoglobin is a well-described gas transport molecule, especially for O2, but also for NO, CO2, and CO, and also acts as a reactive oxygen species scavenger. We previously found Hba-a1 and Hbb mRNA and protein at high levels within mouse periovulatory cumulus cells, but not in cumulus following in vitro maturation. This led us to investigate the temporal and spatial regulation in follicular cells during the periovulatory period. Cumulus-oocyte complexes were collected from equine chorionic gonadotropin/human chorionic gonadotropin-treated peripubertal SV129 female mice and collected and analyzed for gene expression and protein localization at a variety of time points over the periovulatory period. A further cohort matured in vitro with different forms of hemoglobin (ferro- and ferrihemoglobin) under different O2 atmospheric conditions (2%, 5%, and 20% O2) were subsequently fertilized in vitro and cultured to the blastocyst stage. Murine mRNA transcripts for hemoglobin were regulated by stimulation of the ovulatory cascade, in both granulosa and cumulus cells, and expression of HBA1 and HBB was highly significant in human granulosa and cumulus, but erythrocyte cell marker genes were not. Several other genes involved in hemoglobin function were similarly luteinizing hormone-regulated, including genes for heme biosynthesis. Immunohistochemistry revealed a changing localization pattern of HBA-A1 protein in murine cumulus cells and oocytes following the ovulatory signal. Significantly, no positive staining for HBA-A1 protein was observed within in vitro-matured oocytes, but, if coincubated with ferro- or ferrihemoglobin, cytoplasmic HBA-A1 was observed, similar to in vivo-derived oocytes. Addition of ferro-, but not ferrihemoglobin, had a small, positive effect on blastocyst yield, but only under either 2% or 20% O2 gas atmosphere. The identification of hemoglobin within

  20. [Hemoglobin H: laboratory identification].

    PubMed

    Ribeiro, V S; de Araújo, J T

    1992-01-01

    Hemoglobin H (Hb H) disease is an alpha thalassemia form characterized by low synthesis of alpha chain and high beta chain concentration; this unbalance induces the beta chain tetramers formation. Hb H is relatively frequent in Thailand and Greece. Isolated cases have been reported in Chinese, Filipinos, Malaysians. In the Near East occasional cases were observed in Greek Cypriots and Jordanian Arabs. Hb H carriers were found in Italy, Spain, Canada, Indonesia and other countries. In Brazil there are descendants of Italians, Chinese and people of negro origin who are carriers of Hb H. We identified the Hb H by electrophoresis, instability and characteristic inclusion bodies.

  1. Disorders of Human Hemoglobin

    NASA Astrophysics Data System (ADS)

    Bank, Arthur; Mears, J. Gregory; Ramirez, Francesco

    1980-02-01

    Studies of the human hemoglobin system have provided new insights into the regulation of expression of a group of linked human genes, the γ -δ -β globin gene complex in man. In particular, the thalassemia syndromes and related disorders of man are inherited anemias that provide mutations for the study of the regulation of globin gene expression. New methods, including restriction enzyme analysis and cloning of cellular DNA, have made it feasible to define more precisely the structure and organization of the globin genes in cellular DNA. Deletions of specific globin gene fragments have already been found in certain of these disorders and have been applied in prenatal diagnosis.

  2. High-risk glycated hemoglobin trajectories established by mid-20s: findings from a birth cohort study

    PubMed Central

    Shearer, Dara M; Thomson, W Murray; Broadbent, Jonathan M; McLean, Rachael; Poulton, Richie; Mann, Jim

    2016-01-01

    Objective To describe the natural history of glycemia (as measured by glycated hemoglobin (HbA1c)) over 12 years using group-based trajectory modeling (GBTM), and to examine baseline predictors of trajectory. Research design and methods HbA1c data collected at ages 26, 32 and 38 in the long-running, prospective Dunedin Multidisciplinary Health and Development Study were used to assign study members (n=893) to trajectories applying GBTM. A generalization of the model allowed the statistical linking of baseline demographic, smoking and anthropometric characteristics to group membership probability. Results Mean HbA1c increased with age, as did prevalence of prediabetes, diabetes and dysglycemia. The greatest increase occurred between ages 26 and 32. Glycemic health status at age 26 predicted glycemic health status at age 38. 3 HbA1c trajectory groups were identified: ‘low’ (n=98, 11.0%); ‘medium’ (n=482, 54.0%); and ‘high’ (n=313, 35.0%) with mean HbA1c of 29.6, 34.1, and 38.7 mmol/mol, respectively, at age 38. High waist circumference (≥880 mm for women and ≥1020 mm for men), high waist-height ratio (≥0.50), and being a smoker at age 26 predicted membership of the least favorable trajectory over the next 12 years. High body mass index (≥30) at age 26 did not predict of trajectory. Conclusions Trajectories of HbA1c are established relatively early in adulthood. HbA1c levels, waist circumference, waist-height ratio, and smoking status at age 26 are valid clinical predictors for future dysglycemic risk. The identification of HbA1c trajectories and their predictors introduces the possibility of an individualized approach to prevention at an earlier stage than is currently done. PMID:27648291

  3. Elevated hemoglobin A1c Is Associated with Carotid Plaque Vulnerability: Novel Findings from Magnetic Resonance Imaging Study in Hypertensive Stroke Patients

    PubMed Central

    Sun, Beibei; Zhao, Huilin; Liu, Xiaosheng; Lu, Qing; Zhao, Xihai; Pu, Jun; Xu, Jianrong

    2016-01-01

    The association between hemoglobin A1c (HbA1c) level and carotid plaque vulnerability has been rarely studied by magnetic resonance imaging (MRI). The present study of MRI-identified carotid atherosclerotic lesions in hypertensive patients with acute stroke therefore sought to determine the associations between HbA1c level and plaque morphological and compositional characteristics and acute cerebral infarction (ACI) severity. Eighty hypertensive patients with acute stroke were enrolled; stratified into high (≥6.5%) and low (<6.5%) HbA1c groups; and underwent carotid and brain MRI to assess carotid plaque features and ACI volume in the region supplied by the internal carotid artery (ICA) in the symptomatic side. Plaque burden [percent wall volume (PWV), max wall thickness (max-WT)] and lipid-rich necrotic core (LRNC) were larger in the high as compared to the low HbA1c group. High HbA1c was an independent risk factor for the presence of plaque (odds ratio [OR] = 3.71) and LRNC plaque (OR = 7.08). HbA1c independently correlated with ACI severity among patients with ICA region cerebral infarction and carotid plaque. Our study suggested that an elevated HbA1c may have an adverse effect on carotid plaque vulnerability especially those with larger LRNC volumes in hypertensive stroke patients, which might exacerbate the severity of ACIs. PMID:27629481

  4. An Elevated HbA1c Level Is Associated With Short-Term Adverse Outcomes in Patients With Gastrointestinal Cancer and Type 2 Diabetes Mellitus

    PubMed Central

    Huang, Yingchun; Zheng, Huazhen; Chen, Peicong; Yang, Jin; Lin, Shaomin; Liu, Tingting; Chen, Shanwei; Lu, Siqiang; Chen, Junlian; Chen, Wenpu; Peng, Nanhai

    2017-01-01

    Background Although an elevated hemoglobin A1c (HbAc1) level is an independent predictor of worse survival in patients with both digestive cancer and diabetes mellitus, its relationship to short-term prognosis in these patients has not been addressed. This study assessed this relationship in gastrointestinal cancer (GIC) patients with type 2 diabetes mellitus (T2DM). Methods A retrospective review of patients with GIC with or without T2DM from 2004 to 2014 was performed. Patients with T2DM were grouped according to HbA1c level, either normal (mean < 7.0%) or elevated (mean ≥ 7.0%). Age- and sex-matched GIC patients without T2DM served as controls. Results One hundred and eighteen patients aged 33 - 81 years with T2DM met the study eligibility criteria; 51 were in the normal HbA1c group, and 67 were in the elevated HbA1c group. The 91 patients in the non-T2DM group were randomly selected and matched to the T2DM group in terms of admittance date, age, and sex. There was a trend toward a higher 180-day mortality rate in the T2DM group compared with the non-T2DM group (15.3% vs. 7.7%, P = 0.095) and in the elevated HbA1c group compared with the normal HbA1c group (19.4% vs. 9.8%, P = 0.151); however, the differences were not significant. The duration of the hospital stay was longer in patients with T2DM than in those without T2DM (13.2 vs. 8.9 days, P < 0.05) and in patients with elevated versus normal HbA1c levels (14.5 vs. 11.4 days, P < 0.05). Diabetic GIC patients with elevated HbA1c levels had significantly more total postoperative complications than those with normal HbA1c levels (25.4% vs. 9.8%, P < 0.05). In multivariate regression analyses, short-term adverse outcomes were strongly associated with elevated HbA1c levels (odds ratio (OR): 5.276; 95% confidence level (CI): 1.73 - 16.095; P < 0.05) and no strict antidiabetic treatment (OR: 7.65; 95% CI: 2.49 - 23.54; P < 0.001). Conclusion An elevated level of HbA1c significantly correlated with and was an

  5. A case of hemoglobin Hiroshima (β146 histidine to aspartic acid) with compensatory erythremia and undetectable HbA₁c.

    PubMed

    Nishimori, Hisakazu; Harano, Keiko; Wada, Hideho; Takano, Satoshi; Fukuda, Shinji; Takehara, Yukihito; Matsumoto, Hiroshi; Kumagai, Isao; Tanimoto, Mitsune; Takeda, Sho

    2012-06-01

    Hemoglobin (Hb) Hiroshima is an Hb variant that travels rapidly on electrophoresis and shows a fourfold increase in oxygen affinity and a decreased Bohr effect. We encountered a 40-year-old male patient with erythremia and an undetectable HbA(1c) level. The presence of an abnormal hemoglobin molecule was suggested by the results of high-performance liquid chromatography analysis. Subsequent gene analysis by direct sequencing confirmed Hb Hiroshima (β146 histidine → aspartic acid). Caution should be exercised when diagnosing erythremia.

  6. Haemoglobin J-Baltimore can be detected by HbA1c electropherogram but with underestimated HbA1c value.

    PubMed

    Brunel, Valéry; Lahary, Agnčs; Chagraoui, Abdeslam; Thuillez, Christian

    2016-01-01

    Glycated haemoglobin (HbA(1c)) is considered the gold standard for assessing diabetes compensation and treatment. In addition, fortuitous detection of haemoglobin variants during HbA1c measurement is not rare. Recently, two publications reported different conclusions on accuracy of HbA(1c) value using capillary electrophoresis method in presence of haemoglobin J-Baltimore (HbJ).
Here we describe the fortuitous detection of unknown HbJ using capillary electrophoresis for measurement of HbA(1c). A patient followed for gestational diabetes in our laboratory presented unknown haemoglobin on Capillarys 2 Flex Piercing analyser which was identified as HbJ. HbJ is not associated with haematological abnormalities. High Performance Liquid Chromatography methods are known to possibly underestimate HbA(1c) value in the presence of this variant. This variant and its glycated form are clearly distinguished on electropherogram but HbJ was responsible for underestimating the true area of HbA(1c).
 Capillary electrophoresis is a good method for detecting HbJ but does not seem suitable for evaluation of HbA(1C) value in patients in presence of HbJ variant.

  7. Potential Overtreatment of Diabetes Mellitus in Older Adults With Tight Glycemic Control

    PubMed Central

    Lipska, Kasia J.; Ross, Joseph S.; Miao, Yinghui; Shah, Nilay D.; Lee, Sei J.; Steinman, Michael A.

    2015-01-01

    IMPORTANCE In older adults with multiple serious comorbidities and functional limitations, the harms of intensive glycemic control likely exceed the benefits. OBJECTIVES To examine glycemic control levels among older adults with diabetes mellitus by health status and to estimate the prevalence of potential overtreatment of diabetes. DESIGN, SETTING, AND PARTICIPANTS Cross-sectional analysis of the data on 1288 older adults (≥65 years) with diabetes from the National Health and Nutrition Examination Survey (NHANES) from 2001 through 2010 who had a hemoglobin A1c (HbA1c) measurement. All analyses incorporated complex survey design to produce nationally representative estimates. EXPOSURES Health status categories: very complex/poor, based on difficulty with 2 or more activities of daily living or dialysis dependence; complex/intermediate, based on difficulty with 2 or more instrumental activities of daily living or presence of 3 or more chronic conditions; and relatively healthy if none of these were present. MAIN OUTCOMES AND MEASURES Tight glycemic control (HbA1c level, <7%) and use of diabetes medications likely to result in hypoglycemia (insulin or sulfonylureas). RESULTS Of 1288 older adults with diabetes, 50.7% (95% CI, 46.6%–54.8%), representing 3.1 million (95% CI, 2.7–3.5), were relatively healthy, 28.1% (95% CI, 24.8%–31.5%), representing 1.7 million (95% CI, 1.4–2.0), had complex/intermediate health, and 21.2% (95% CI, 18.3%–24.4%), representing 1.3 million (95% CI, 1.1–1.5), had very complex/poor health. Overall, 61.5% (95% CI, 57.5%–65.3%), representing 3.8 million (95% CI, 3.4–4.2), had an HbA1c level of less than 7%; this proportion did not differ across health status categories (62.8% [95% CI, 56.9%–68.3%]) were relatively healthy, 63.0% (95% CI, 57.0%–68.6%) had complex/intermediate health, and 56.4% (95% CI, 49.7%–62.9%) had very complex/poor health (P = .26). Of the older adults with an HbA1c level of less than 7%, 54.9% (95

  8. Factors associated with glycemic control in adult type 1 diabetes patients treated with insulin pump therapy.

    PubMed

    Matejko, Bartłomiej; Skupien, Jan; Mrozińska, Sandra; Grzanka, Małgorzata; Cyganek, Katarzyna; Kiec-Wilk, Beata; Malecki, Maciej T; Klupa, Tomasz

    2015-02-01

    Continuous subcutaneous insulin infusion (CSII) by insulin pump seems to improve glycemia and quality of life as compared to conventional insulin therapy in type 1 diabetes (T1DM). However, while many T1DM subjects achieve excellent glycemic control, some others cannot reach recommended goals. In a retrospective analysis, we searched for factors associated with glycemic control in T1DM patients treated with insulin pump therapy. Data from 192 patients (133 women and 59 men) treated with personal insulin pumps at the Department of Metabolic Diseases, University Hospital, Krakow, Poland were analyzed. Sources of information included medical records, memory read-outs from insulin pumps and data from glucose meters. Univariate, multivariate linear and logistic regression analysis for the association with hemoglobin A1c (HbA1c) level were performed. The mean age of the subjects was 28.9 (±11.2) years, the mean duration of T1DM-14.6 (±7.6) years, mean body mass index-23.5 (±3.1) kg/m2. The mean HbA1c level in the entire study group was 7.4% (57 mmol/mol). In the multivariate linear regression analysis, HbA1c correlated with the mean number of daily blood glucose measurements, number of hypoglycemic episodes per 100 blood glucose measurements, age at the examination, and continuous glucose monitoring system use. Multivariate logistic regression analysis for reaching the therapeutic target of HbA1c<7.0% (53 mmol/mol) showed that the independent predictors of achieving this goal included the same four variables. In a large clinical observation, we identified that patient-related and technological factors associated with glycemic control in adult pump-treated T1DM subjects.

  9. THE RENAL HANDLING OF HEMOGLOBIN

    PubMed Central

    Bunn, H. Franklin; Jandl, James H.

    1969-01-01

    The fate of small doses of isotopically labeled isologous hemoglobin was studied in the rat. When haptoglobin depleted animals were given 2.0 mg of 59Fe hemoglobin intravenously, nearly half was trapped by the kidneys. Kidney 59Fe activity disappeared slowly over several weeks. Whatever iron was lost from the kidneys was largely reutilized. In contrast, the porphyrin of hemoglobin absorbed by the kidneys appeared to be rapidly catabolized, since 5 hr after the injection of 14C or 59Fe heme-labeled hemoglobin only a small fraction was recovered as hematin. Likewise, after injection of globin-labeled hemoglobin, rapid disappearance of kidney protein activity indicated that the absorbed globin was readily catabolized in situ. PMID:5778790

  10. Integrative health coaching: a behavior skills approach that improves HbA1c and pharmacy claims-derived medication adherence

    PubMed Central

    Wolever, Ruth Q; Dreusicke, Mark H

    2016-01-01

    Objective Medication adherence requires underlying behavior skills and a supporting mindset that may not be addressed with education or reminders. Founded in the study of internal motivation and health psychology, integrative health coaching (IHC) helps patients gain insight into their behaviors and make long-term, sustainable lifestyle changes. The purpose of the study is to determine whether IHC improves oral medication adherence, glycated hemoglobin (HbA1c), and psychosocial measures, and to assess whether adherence changes are sustained after the intervention. Methods Using a prospective observational design, participants (n=56) received 14 coaching calls by telephone over 6 months. Medication possession ratio (MPR) was calculated for time intervals before, during, and after the intervention. HbA1c and patient-reported psychosocial outcomes were obtained to test interactions with MPR. Results Medication adherence (MPR) increased from 0.74±0.197 to 0.85±0.155 during coaching, and was sustained at 0.82±0.175 during a 6-month period after the study. Better adherence correlated with a greater decrease in HbA1c. HbA1c decreased from 8.0±1.92% to 7.7±1.70% over the 6-month intervention. All psychosocial measures showed significant improvement. In addition to discussing medication adherence strategies with their coach, patients discussed nutrition and exercise (86.9% of calls), stress management (39.8%), and social support and relationships (15.4%). Conclusions IHC targets internal motivation and supports behavior change by facilitating patients’ insight into their own behaviors, and it uses this insight to foster self-efficacy. This approach may yield sustainable results for medication adherence and warrants further exploration for health-related behavior change. PMID:27239318

  11. Application of sigma metrics for the assessment of quality assurance using the MQ-2000 PT HbA1c analyzer

    PubMed Central

    Huysal, Kağan; Budak, Yasemin U

    2015-01-01

    Introduction Glycosylated hemoglobin (HbA1c) concentrations measured in clinical chemistry laboratories show large differences between their interlaboratory reported values. Laboratory measurements of quality performance should be based on quantitative data. The sigma metrics model provides an objective method for the assessment of current HbA1c assays and is useful in quality management planning. The aim of our study was to evaluate the analytical performance of the MQ-2000 PT HbA1c analyzer test results in the context of our operating conditions on the sigma scale. Materials and methods The coefficient of variation was determined from the calculated mean and standard deviation evaluated from internal quality control (QC) (N = 168 days) (Shanghai Huachen Biological Reagent Co. Ltd, China) data, and records of external quality data (KBUDEK, İstanbul, Turkey) measured in the period from May to November 2013 were used to determine the bias. The resulting data and total allowable error rate (TEA = 10%) from the Clinical Laboratory Improvement Amendments of 1988 (CLIA’88) were used to calculate the sigma level. Results The calculated coefficient of variations (CVs) at the two levels, normal (QC1 = 36.6 ± 2.38 mmol/mol) and pathological (QC2 = 84.7 ± 2.68 mmol/mol), were 6.5% and 3.1%, respectively. The average bias between the external QC and MQ-2000 PT during the study period was 4.3%. The calculated average sigma value was 1.19. Conclusions The MQ-2000 PT HbA1c is a new analyser in the market; there is need for improvement and the method should be controlled with greater attention to ensure quality. PMID:26527591

  12. Glycated hemoglobin detection with electrochemical sensing amplified by gold nanoparticles embedded N-doped graphene nanosheet.

    PubMed

    Jain, Utkarsh; Chauhan, Nidhi

    2017-03-15

    In the diabetic patients the level of glucose must be determined without any short term fluctuations. The level of Glycated hemoglobin (HbA1c) is accordingly examined for checking diabetes mellitus. HbA1c is considered one of the primarily factor to discern the concentration of average plasma glucose over a long-drawn-out period. In our work, we describe a construction of biosensor which is based on fructosyl amino-acid oxidase (FAO) immobilized nitrogen-doped graphene/gold nanoparticles (AuNPs)/fluorine doped tin oxide (FTO) glass electrode. This constructed biosensor exhibits a wide linear range of 0.3 to 2000μM in response to HbA1c at +0.2V. Consequently, the detection limit of 0.2μM and good stability (4 months) were achieved. The electrocatalytic activity of this sensor was good as a result of synergistic effect of graphene and AuNPs (2D and 0D nanomaterials). The charge transfer resistance was decreased which was observed by electrochemical impedance spectroscopy (EIS) study. The graphene/AuNPs composites film reveals a distinguished electrochemical response to fructosyl valine (FV) which demonstrates a promising application for electrochemical detection of HbA1c in human blood samples.

  13. Is There a Role for HbA1c in Pregnancy?

    PubMed

    Hughes, Ruth C E; Rowan, Janet; Florkowski, Chris M

    2016-01-01

    Outside pregnancy, HbA1c analysis is used for monitoring, screening for and diagnosing diabetes and prediabetes. During pregnancy, the role for HbA1c analysis is not yet established. Physiological changes lower HbA1c levels, and pregnancy-specific reference ranges may need to be recognised. Other factors that influence HbA1c are also important to consider, particularly since emerging data suggest that, in early pregnancy, HbA1c elevations close to the reference range may both identify women with underlying hyperglycaemia and be associated with adverse pregnancy outcomes. In later pregnancy, HbA1c analysis is less useful than an oral glucose tolerance test (OGTT) at detecting gestational diabetes. Postpartum, HbA1c analysis detects fewer women with abnormal glucose tolerance than an OGTT, but the ease of testing may improve follow-up rates and combining HbA1c analysis with fasting plasma glucose or waist circumference may improve detection rates. This article discusses the relevance of HbA1c testing at different stages of pregnancy.

  14. Gene Turnover in the Avian Globin Gene Families and Evolutionary Changes in Hemoglobin Isoform Expression

    PubMed Central

    Opazo, Juan C.; Hoffmann, Federico G.; Natarajan, Chandrasekhar; Witt, Christopher C.; Berenbrink, Michael; Storz, Jay F.

    2015-01-01

    The apparent stasis in the evolution of avian chromosomes suggests that birds may have experienced relatively low rates of gene gain and loss in multigene families. To investigate this possibility and to explore the phenotypic consequences of variation in gene copy number, we examined evolutionary changes in the families of genes that encode the α- and β-type subunits of hemoglobin (Hb), the tetrameric α2β2 protein responsible for blood-O2 transport. A comparative genomic analysis of 52 bird species revealed that the size and membership composition of the α- and β-globin gene families have remained remarkably constant during approximately 100 My of avian evolution. Most interspecific variation in gene content is attributable to multiple independent inactivations of the αD-globin gene, which encodes the α-chain subunit of a functionally distinct Hb isoform (HbD) that is expressed in both embryonic and definitive erythrocytes. Due to consistent differences in O2-binding properties between HbD and the major adult-expressed Hb isoform, HbA (which incorporates products of the αA-globin gene), recurrent losses of αD-globin contribute to among-species variation in blood-O2 affinity. Analysis of HbA/HbD expression levels in the red blood cells of 122 bird species revealed high variability among lineages and strong phylogenetic signal. In comparison with the homologous gene clusters in mammals, the low retention rate for lineage-specific gene duplicates in the avian globin gene clusters suggests that the developmental regulation of Hb synthesis in birds may be more highly conserved, with orthologous genes having similar stage-specific expression profiles and similar functional properties in disparate taxa. PMID:25502940

  15. Gene turnover in the avian globin gene families and evolutionary changes in hemoglobin isoform expression.

    PubMed

    Opazo, Juan C; Hoffmann, Federico G; Natarajan, Chandrasekhar; Witt, Christopher C; Berenbrink, Michael; Storz, Jay F

    2015-04-01

    The apparent stasis in the evolution of avian chromosomes suggests that birds may have experienced relatively low rates of gene gain and loss in multigene families. To investigate this possibility and to explore the phenotypic consequences of variation in gene copy number, we examined evolutionary changes in the families of genes that encode the α- and β-type subunits of hemoglobin (Hb), the tetrameric α2β2 protein responsible for blood-O2 transport. A comparative genomic analysis of 52 bird species revealed that the size and membership composition of the α- and β-globin gene families have remained remarkably constant during approximately 100 My of avian evolution. Most interspecific variation in gene content is attributable to multiple independent inactivations of the α(D)-globin gene, which encodes the α-chain subunit of a functionally distinct Hb isoform (HbD) that is expressed in both embryonic and definitive erythrocytes. Due to consistent differences in O2-binding properties between HbD and the major adult-expressed Hb isoform, HbA (which incorporates products of the α(A)-globin gene), recurrent losses of α(D)-globin contribute to among-species variation in blood-O2 affinity. Analysis of HbA/HbD expression levels in the red blood cells of 122 bird species revealed high variability among lineages and strong phylogenetic signal. In comparison with the homologous gene clusters in mammals, the low retention rate for lineage-specific gene duplicates in the avian globin gene clusters suggests that the developmental regulation of Hb synthesis in birds may be more highly conserved, with orthologous genes having similar stage-specific expression profiles and similar functional properties in disparate taxa.

  16. Therapeutic levels of fetal hemoglobin in erythroid progeny of β-thalassemic CD34+ cells after lentiviral vector-mediated gene transfer

    PubMed Central

    Wilber, Andrew; Hargrove, Phillip W.; Kim, Yoon-Sang; Riberdy, Janice M.; Sankaran, Vijay G.; Papanikolaou, Eleni; Georgomanoli, Maria; Anagnou, Nicholas P.; Orkin, Stuart H.; Nienhuis, Arthur W.

    2011-01-01

    β-Thalassemia major results from severely reduced or absent expression of the β-chain of adult hemoglobin (α2β2;HbA). Increased levels of fetal hemoglobin (α2γ2;HbF), such as occurs with hereditary persistence of HbF, ameliorate the severity of β-thalassemia, raising the potential for genetic therapy directed at enhancing HbF. We used an in vitro model of human erythropoiesis to assay for enhanced production of HbF after gene delivery into CD34+ cells obtained from mobilized peripheral blood of normal adults or steady-state bone marrow from patients with β-thalassemia major. Lentiviral vectors encoding (1) a human γ-globin gene with or without an insulator, (2) a synthetic zinc-finger transcription factor designed to interact with the γ-globin gene promoters, or (3) a short-hairpin RNA targeting the γ-globin gene repressor, BCL11A, were tested. Erythroid progeny of normal CD34+ cells demonstrated levels of HbF up to 21% per vector copy. For β-thalassemic CD34+ cells, similar gene transfer efficiencies achieved HbF production ranging from 45% to 60%, resulting in up to a 3-fold increase in the total cellular Hb content. These observations suggest that both lentiviral-mediated γ-globin gene addition and genetic reactivation of endogenous γ-globin genes have potential to provide therapeutic HbF levels to patients with β-globin deficiency. PMID:21156846

  17. Prediction of glycated hemoglobin levels at 3 months after metabolic surgery based on the 7-day plasma metabolic profile.

    PubMed

    Kwon, Hyuk Nam; Lee, Yeon Ji; Kang, Ju-Hee; Choi, Ji-Ho; An, Yong Jin; Kang, Sunmi; Lee, Dae Hyun; Suh, Young Ju; Heo, Yoonseok; Park, Sunghyouk

    2014-01-01

    Metabolic surgery has been shown to provide better glycemic control for type 2 diabetes than conventional therapies. Still, the outcomes of the surgery are variable, and prognostic markers reflecting the metabolic changes by the surgery are yet to be established. NMR-based plasma metabolomics followed by multivariate regression was used to test the correlation between the metabolomic profile at 7-days after surgery and glycated hemoglobin (HbA1c) levels at 3-months (and up to 12 months with less patients), and to identify the relevant markers. Metabolomic profiles at 7-days could differentiate the patients according to the HbA1c improvement status at 3-months. The HbA1c values were predicted based on the metabolomics profile with partial least square regression, and found to be correlated with the observed values. Metabolite analysis suggested that 3-Hydroxybutyrate (3-HB) and glucose contributes to this prediction, and the [3-HB]/[glucose] exhibited a modest to good correlation with the HbA1c level at 3-months. The prediction of 3-month HbA1c using 7-day metabolomic profile and the suggested new criterion [3-HB]/[glucose] could augment current prognostic modalities and help clinicians decide if drug therapy is necessary.

  18. A Novel Glycated Hemoglobin A1c-Lowering Traditional Chinese Medicinal Formula, Identified by Translational Medicine Study

    PubMed Central

    Li, Tsai-Chung; Li, Chia-Cheng; Huang, Hui-Chi; Chen, Jaw-Chyun; Ho, Tin-Yun

    2014-01-01

    Diabetes is a chronic metabolic disorder that has a significant impact on the health care system. The reduction of glycated hemoglobin A1c is highly associated with the improvements of glycemic control and diabetic complications. In this study, we identified a traditional Chinese medicinal formula with a HbA1c-lowering potential from clinical evidences. By surveying 9,973 diabetic patients enrolled in Taiwan Diabetic Care Management Program, we found that Chu-Yeh-Shih-Kao-Tang (CYSKT) significantly reduced HbA1c values in diabetic patients. CYSKT reduced the levels of HbA1c and fasting blood glucose, and stimulated the blood glucose clearance in type 2 diabetic mice. CYSKT affected the expressions of genes associated with insulin signaling pathway, increased the amount of phosphorylated insulin receptor in cells and tissues, and stimulated the translocation of glucose transporter 4. Moreover, CYSKT affected the expressions of genes related to diabetic complications, improved the levels of renal function indexes, and increased the survival rate of diabetic mice. In conclusion, this was a translational medicine study that applied a “bedside-to-bench” approach to identify a novel HbA1c-lowering formula. Our findings suggested that oral administration of CYSKT affected insulin signaling pathway, decreased HbA1c and blood glucose levels, and consequently reduced mortality rate in type 2 diabetic mice. PMID:25133699

  19. What Do We Need beyond Hemoglobin A1c to Get the Complete Picture of Glycemia in People with Diabetes?

    PubMed Central

    Hinzmann, Rolf; Schlaeger, Christof; Tran, Cam Tuan

    2012-01-01

    Hemoglobin A1c (HbA1c) is currently the most commonly used marker for the determination of the glycemic status in people with diabetes and it is frequently used to guide therapy and especially medical treatment of people with diabetes. The measurement of HbA1c has reached a high level of analytical quality and, therefore, this biomarker is currently also suggested to be used for the diagnosis of diabetes. Nevertheless, it is crucial for people with diabetes and their treating physicians to be aware of possible interferences during its measurement as well as physiological or pathological factors that contribute to the HbA1c concentration without being related to glycemia, which are discussed in this review. We performed a comprehensive review of the literature based on PubMed searches on HbA1c in the treatment and diagnosis of diabetes including its most relevant limitations, glycemic variability and self-monitoring of blood glucose (SMBG). Although the high analytical quality of the HbA1c test is widely acknowledged, the clinical relevance of this marker regarding risk reduction of cardiovascular morbidity and mortality is still under debate. In this respect, we argue that glycemic variability as a further risk factor should deserve more attention in the treatment of diabetes. PMID:23055818

  20. Factors Influencing Changes in Hemoglobin A1c and Body Weight During Treatment of Type 2 Diabetes With Ipragliflozin: Interim Analysis of the ASSIGN-K Study

    PubMed Central

    Iemitsu, Kotaro; Iizuka, Takashi; Takihata, Masahiro; Takai, Masahiko; Nakajima, Shigeru; Minami, Nobuaki; Umezawa, Shinichi; Kanamori, Akira; Takeda, Hiroshi; Kawata, Takehiro; Ito, Shogo; Kikuchi, Taisuke; Amemiya, Hikaru; Kaneshiro, Mizuki; Mokubo, Atsuko; Takuma, Tetsuro; Machimura, Hideo; Tanaka, Keiji; Asakura, Taro; Kubota, Akira; Aoyagi, Sachio; Hoshino, Kazuhiko; Ishikawa, Masashi; Obana, Mitsuo; Sasai, Nobuo; Kaneshige, Hideaki; Miyakawa, Masaaki; Tanaka, Yasushi; Terauchi, Yasuo; Matsuba, Ikuro

    2016-01-01

    Background Ipragliflozin is a selective sodium glucose co-transporter 2 (SGLT2) inhibitor that blocks glucose reabsorption in the proximal tubules. SGLT2 inhibitors are expected to be effective in patients with insulin resistance and obesity, but it is important to select treatment according to patient background factors that minimizes the risk of adverse events. There have been a limited number of investigations into the relationship between the clinical efficacy (reducing hemoglobin A1c (HbA1c) and body weight (BW)) or safety of SGLT2 inhibitors and patient characteristics. Methods ASSIGN-K is an investigator-initiated, multicenter, prospective observational study examining the efficacy and safety of ipragliflozin (50 - 100 mg/day for 52 weeks) in Japanese patients with type 2 diabetes mellitus (T2DM) who had inadequate glycemic control with HbA1c ≥ 6.0% (National Glycohemoglobin Standardization Program) despite diet and exercise therapy or diet and exercise plus antidiabetic drug therapy. We conducted an interim analysis of the relationship between changes in HbA1c or BW and characteristics in patients who had been on treatment for more than 12 weeks. Results In 257 patients completing 12 weeks of treatment, HbA1c decreased significantly from 8.23% to 7.55% (-0.68%, P < 0.01). The change in HbA1c after 12 weeks was -0.17%, -0.33%, and -1.16% when baseline HbA1c was < 7%, 7% to < 8%, and ≥ 8%, respectively (P < 0.05, P < 0.01, and P < 0.01, respectively), and -1.30%, -0.62%, and -0.62% when baseline body mass index (BMI) was < 25, 25 to < 30, and ≥ 30, respectively (all P < 0.01). Stratified analysis showed that age, gender, or BMI did not have a significant influence on the improvement in HbA1c. Multiple regression analysis showed that reduction in HbA1c was greater as baseline HbA1c increased and the duration of diabetes decreased. A higher baseline HbA1c was associated with less weight loss. Conclusions Ipragliflozin significantly improved HbA1c in

  1. Delayed treatment of hemoglobin neurotoxicity.

    PubMed

    Regan, Raymond F; Rogers, Bret

    2003-01-01

    Hemoglobin is an oxidative neurotoxin that may contribute to cell injury after CNS trauma and hemorrhagic stroke. Prior studies have demonstrated that concomitant treatment with iron-chelating antioxidants prevents its neurotoxicity. However, the efficacy of these agents when applied hours after hemoglobin has not been determined, and is the subject of the present investigation. Consistent with prior observations, an increase in reactive oxygen species generation, detected by 2',7'-dichlorofluorescin oxidation, was observed when mixed neuronal/astrocyte cultures prepared from mouse cortex were exposed to hemoglobin alone. However, this oxidative stress developed slowly. A significant increase in the dichlorofluorescein signal compared with control, untreated cultures was not observed until four hours after addition of hemoglobin, and was followed by loss of membrane integrity and propidium iodide staining. Treating cultures with the 21-aminosteroid U74500A or the ferric iron chelator deferoxamine four hours after initiating hemoglobin treatment markedly attenuated reactive oxygen species production within 2 h. Continuous exposure to 5 micro M hemoglobin for 24 h resulted in death of about three-quarters of neurons, without injuring astrocytes. Most neuronal loss was prevented by concomitant treatment with U74500A; its effect was not significantly attenuated if treatment was delayed for 2-4 h, and it still prevented over half of neuronal death if treatment was delayed for 8 h. Similar neuroprotection was produced by delayed treatment with deferoxamine or the lipid-soluble iron chelator phenanthroline. None of these agents had any effect on neuronal death when added to cultures 12 h after hemoglobin. These results suggest that hemoglobin is a potent but slowly-acting neurotoxin. The delayed onset of hemoglobin neurotoxicity may make it an attractive target for therapeutic intervention.

  2. Serum iron, total iron binding capacity, plasma copper and hemoglobin types in anemic and poikilocytic calves.

    PubMed Central

    McGillivray, S R; Searcy, G P; Hirsch, V M

    1985-01-01

    Ninety-eight calves were studied to determine if anemia and poikilocytosis were related to iron or copper status or hemoglobin type. No significant differences were found in serum iron, total iron binding capacity, marrow iron, plasma copper or hemoglobin type between affected and normal calves. Poikilocytes were strongly inversely correlated (-0.9177) with age. Calves less than six weeks of age had more poikilocytes, lower serum iron, higher total iron binding capacity, less adult hemoglobin and more neonatal and fetal hemoglobin than calves greater than six weeks of age. Images Fig. 1. PMID:2412677

  3. Prevalence of Elevated Glycated Hemoglobin Concentrations in the Polycystic Ovary Syndrome: Anthropometrical and Metabolic Relationship in Amazonian Women

    PubMed Central

    de Medeiros, Sebastiao Freitas; Yamamoto, Marcia Marly Winck; Bueno, Herica Bernardes; Belizario, Danilla; Barbosa, Jacklyne Silva

    2014-01-01

    Background To determine the prevalence of elevated glycated hemoglobin (HbA1c) and to examine its relationship with other carbohydrate metabolic parameter among Brazilian women with polycystic ovary syndrome (PCOS). Methods A cross-sectional study including 288 PCOS patients was conducted. Anthropometrical, clinical, biochemical and endocrine parameters were evaluated. Results The mean age was 26.92 ± 5.51 years. HbA1c mean concentration was 5.83±1.34%. In 38.54% of patients, HbA1c was ≥ 5.7%. HbA1c was positively correlated with body weight (r = 0.142, P = 0.017), body mass index (P = 0.000), waist:hip ratio (P = 0.000), fat mass (P = 0.000), conicity index (P = 0.000), triglyceride (P = 0.001), C-peptide (P = 0.000), total testosterone (P = 0.003), free testosterone (P = 0.000), free androgen index (P = 0.006) and fasting insulin (P = 0.025). Using the oral glucose tolerance test, HbA1c showed positive correlation with glucose concentrations at any point in time (P < 0.05). Conclusions HbA1c was elevated in nearly 40% of PCOS patients and it showed positive correlation with several anthropometric and metabolic factors and androgen levels. The current study provides further evidence that HbA1C is higher in PCOS patients and may have a potential role in the prediction of dysglycemic disease in these women. PMID:24883154

  4. Non-invasive hemoglobin monitoring.

    PubMed

    Joseph, Bellal; Haider, Ansab; Rhee, Peter

    2016-09-01

    Technology has transformed the practice of medicine and surgery in particular over the last several decades. This change in practice has allowed diagnostic and therapeutic tests to be performed less invasively. Hemoglobin monitoring remains one of the most commonly performed diagnostic tests in the United States. Recently, non-invasive hemoglobin monitoring technology has gained popularity. The aim of this article is to review the principles of how this technology works, pros and cons, and the implications of non-invasive hemoglobin technology particularly in trauma surgery.

  5. Insights into Hemoglobin Assembly through in Vivo Mutagenesis of α-Hemoglobin Stabilizing Protein*

    PubMed Central

    Khandros, Eugene; Mollan, Todd L.; Yu, Xiang; Wang, Xiaomei; Yao, Yu; D'Souza, Janine; Gell, David A.; Olson, John S.; Weiss, Mitchell J.

    2012-01-01

    α-Hemoglobin stabilizing protein (AHSP) is believed to facilitate adult Hemoglobin A assembly and protect against toxic free α-globin subunits. Recombinant AHSP binds multiple forms of free α-globin to stabilize their structures and inhibit precipitation. However, AHSP also stimulates autooxidation of αO2 subunit and its rapid conversion to a partially unfolded bishistidyl hemichrome structure. To investigate these biochemical properties, we altered the evolutionarily conserved AHSP proline 30 in recombinantly expressed proteins and introduced identical mutations into the endogenous murine Ahsp gene. In vitro, the P30W AHSP variant bound oxygenated α chains with 30-fold increased affinity. Both P30W and P30A mutant proteins also caused decreased rates of αO2 autooxidation as compared with wild-type AHSP. Despite these abnormalities, mice harboring P30A or P30W Ahsp mutations exhibited no detectable defects in erythropoiesis at steady state or during induced stresses. Further biochemical studies revealed that the AHSP P30A and P30W substitutions had minimal effects on AHSP interactions with ferric α subunits. Together, our findings indicate that the ability of AHSP to stabilize nascent α chain folding intermediates prior to hemin reduction and incorporation into adult Hemoglobin A is physiologically more important than AHSP interactions with ferrous αO2 subunits. PMID:22287545

  6. In-Depth Comparative Characterization of Hemoglobin Glycation in Normal and Diabetic Bloods by LC-MSMS

    NASA Astrophysics Data System (ADS)

    Wang, Shih-Hao; Wang, Tzu-Fan; Wu, Chih-Hsing; Chen, Shu-Hui

    2014-05-01

    The glycation level at β-Val-1 of the hemoglobin β chain in human blood (HbA1c%) is used to diagnose diabetes and other diseases. However, hemoglobin glycation occurs on multiple sites on different isoforms with different kinetics, but its differential profile has not been clearly demonstrated. In this study, hemoglobin was extracted from the blood of normal and diabetic individuals by protein precipitation. Triplicate solutions prepared from each sample were directly analyzed or digested with multiple enzymes and then analyzed by nano-LC/MS via bottom-up approach for side-by-side characterization. Intact hemoglobin analysis indicated a single glucose-dominant glycation, which showed good correlation with the HbA1c% values. Moreover, full sequence (100 %) of α/β globin was mapped and seven glycation sites were unambiguously assigned. In addition to β-Val-1, two other major sites at α-Lys-61 and β-Lys-66, which contain the common sequence HGK K, and four minor sites (<1 %) on α-Val-1, β-Lys-132, α-Lys-127, and α-Lys-40 were identified. All sites were shown to exhibit similar patterns of site distribution despite different glucose levels. Both the intact mass measurement and bottom-up data consistently indicated that the total glycation percentage of the β-globin was twice higher than the α-globin. Using molecular modeling, the 3D structure of the consensus sequence (HGK K) was shown to contain a phosphate triangle cavity, which helps to catalyze the glycation reaction. For the first time, hemoglobin glycation in normal and diabetic bloods was comparatively characterized in-depth with 100 % sequence coverage. The results provide insight about the HbA1c parameter and help define the new and old markers.

  7. Phenotypic expression of hemoglobin A2 in beta-thalassemia trait with iron deficiency.

    PubMed

    Madan, N; Sikka, M; Sharma, S; Rusia, U

    1998-09-01

    Iron status was estimated in 463 heterozygous beta-thalassemics to delineate the effect of iron deficiency on the expression of hemoglobin A2 (HbA2) in these patients. One hundred and twenty-six (27.2%) patients with the trait were iron deficient. These iron-deficient patients had a significantly (p < 0.0002) higher prevalence of anemia (90.5%) compared with iron-replete patients with the trait (71.5%). The mean hemoglobin (Hb) concentration, MCV, and MCH were significantly (p < 0.0001) lower in patients with beta-thalassemia traits (BTT) who had iron deficiency than in those without iron deficiency. Mean RBC count and MCHC did not differ in the two groups. Mean HbA2 was not significantly different in the two groups of patients with the trait and was elevated (>3.5%) in all but one heterozygote investigated. Mean HbA2/cell was significantly (p < 0.05) lower in BTT patients with iron deficiency than in patients without iron deficiency. The presence of iron deficiency did not preclude the detection of BTT in this population. The effect of iron deficiency in BTT was apparent as a significant lowering of the Hb concentration and an increased prevalence of anemia. Iron therapy is warranted for BTT patients with iron-deficiency traits and would help to significantly raise their Hb concentration. The elevation of HbA2 was striking and could be used with reliability in making the diagnosis of BTT even in the presence of iron deficiency.

  8. Glycated hemoglobin and its spinoffs: Cardiovascular disease markers or risk factors?

    PubMed Central

    Saleh, Jumana

    2015-01-01

    Atherosclerosis is a major complication of diabetes, increasing the risk of cardiovascular related morbidities and mortalities. The hallmark of diabetes is hyperglycemia which duration is best predicted by elevated glycated haemoglobin A1C (HbA1C) levels. Diabetic complications are usually attributed to oxidative stress associated with glycation of major structural and functional proteins. This non-enzymatic glycation of long lived proteins such as collagen, albumin, fibrinogen, liver enzymes and globulins result in the formation of early and advanced glycation end products (AGEs) associated with the production of myriads of free radicles and oxidants that have detrimental effects leading to diabetic complications. AGEs have been extensively discussed in the literature as etiological factors in the advancement of atherogenic events. Mechanisms described include the effects of glycation on protein structure and function that lead to defective receptor binding, impairment of immune system and enzyme function and alteration of basement membrane structural integrity. Hemoglobin (Hb) is a major circulating protein susceptible to glycation. Glycated Hb, namely HbA1C is used as a useful tool in the diagnosis of diabetes progression. Many studies have shown strong positive associations between elevated HbA1C levels and existing cardiovascular disease and major risk factors. Also, several studies presented HbA1C as an independent predictor of cardiovascular risk. In spite of extensive reports on positive associations, limited evidence is available considering the role of glycated Hb in the etiology of atherosclerosis. This editorial highlights potential mechanisms by which glycated hemoglobin may contribute, as a causative factor, to the progression of atherosclerosis in diabetics. PMID:26322184

  9. Glycated hemoglobin and its spinoffs: Cardiovascular disease markers or risk factors?

    PubMed

    Saleh, Jumana

    2015-08-26

    Atherosclerosis is a major complication of diabetes, increasing the risk of cardiovascular related morbidities and mortalities. The hallmark of diabetes is hyperglycemia which duration is best predicted by elevated glycated haemoglobin A1C (HbA1C) levels. Diabetic complications are usually attributed to oxidative stress associated with glycation of major structural and functional proteins. This non-enzymatic glycation of long lived proteins such as collagen, albumin, fibrinogen, liver enzymes and globulins result in the formation of early and advanced glycation end products (AGEs) associated with the production of myriads of free radicles and oxidants that have detrimental effects leading to diabetic complications. AGEs have been extensively discussed in the literature as etiological factors in the advancement of atherogenic events. Mechanisms described include the effects of glycation on protein structure and function that lead to defective receptor binding, impairment of immune system and enzyme function and alteration of basement membrane structural integrity. Hemoglobin (Hb) is a major circulating protein susceptible to glycation. Glycated Hb, namely HbA1C is used as a useful tool in the diagnosis of diabetes progression. Many studies have shown strong positive associations between elevated HbA1C levels and existing cardiovascular disease and major risk factors. Also, several studies presented HbA1C as an independent predictor of cardiovascular risk. In spite of extensive reports on positive associations, limited evidence is available considering the role of glycated Hb in the etiology of atherosclerosis. This editorial highlights potential mechanisms by which glycated hemoglobin may contribute, as a causative factor, to the progression of atherosclerosis in diabetics.

  10. Achieving comparability with IFCC reference method for the measurement of hemoglobin A1c by use of an improved isotope-dilution mass spectrometry method.

    PubMed

    Liu, Hong; Wong, Lingkai; Yong, Sharon; Liu, Qinde; Lee, Tong Kooi

    2015-10-01

    The development of reference measurement methods for hemoglobin A1c (HbA1c) is important for quality assurance in diabetes management. The IFCC reference method using purified proteins as calibration standards is the recommended accuracy-based reference method for the standardization of HbA1c measurement. We developed a highly precise and accurate liquid chromatography-isotope-dilution tandem mass spectrometry (LC-IDMS/MS) procedure, which can serve as an alternative accuracy-based method for HbA1c measurement. In this method, enzymatic proteolysis was applied to sample preparation, followed by LC-IDMS/MS measurement of hemoglobin A0 (HbA0) and HbA1c, using two "signature" hexapeptides for calibration. The concentrations of the signature hexapeptide calibration solutions were, in turn, determined using a hydrolysis method with HCl, followed by LC-IDMS/MS measurement using amino acid solutions as calibration standards. These solutions were gravimetrically prepared from pure amino acid certified reference materials (CRMs). The developed LC-IDMS/MS method was used in participation in an IFCC ring trial for reference laboratories (RELA 2013 and 2014) for HbA1c, where our results were compared with those using the IFCC reference method. The deviations were found to be 0.4-1.7 mmol mol(-1) [or 0.04-0.16% in National Glygohemoglobin Standardization Program (NGSP) units], revealing good comparability with the IFCC reference method. The relative expanded uncertainty of the LC-IDMS/MS was in the range of 2.6% to 2.8% (1.6% to 2.2% after converting to NGSP units). With excellent method precision, good comparability with the IFCC reference method, and a small measurement uncertainty, the developed LC-IDMS/MS method may be used as an alternative accuracy-based reference method for HbA1c measurement.

  11. Association of Genomic Instability with HbA1c levels and Medication in Diabetic Patients

    PubMed Central

    Grindel, Annemarie; Brath, Helmut; Nersesyan, Armen; Knasmueller, Siegfried; Wagner, Karl-Heinz

    2017-01-01

    Diabetes Mellitus type 2 (DM2) is associated with increased cancer risk. Instability of the genetic material plays a key role in the aetiology of human cancer. This study aimed to analyse genomic instability with the micronucleus cytome assay in exfoliated buccal cells depending on glycated haemoglobin (HbA1c) levels and medication in 146 female DM2 patients. The occurrence of micronuclei was significantly increased in DM2 patients compared to healthy controls. Furthermore, it was doubled in DM2 patients with HbA1c > 7.5% compared to subjects with HbA1c ≤ 7.5%. Positive correlations were found between micronuclei frequencies and HbA1c as well as fasting plasma glucose. Patients under insulin treatment showed a two-fold increase in micronuclei frequencies compared to subjects under first-line medication (no drugs or monotherapy with non-insulin medication). However, after separation of HbA1c (cut-off 7.5%) only patients with severe DM2 characterised by high HbA1c and insulin treatment showed higher micronuclei frequencies but not patients with insulin treatment and low HbA1c. We demonstrated that the severity of DM2 accompanied by elevated micronuclei frequencies predict a possible enhanced cancer risk among female DM2 patients. Therapy, therefore, should focus on a strict HbA1c control and personalised medical treatments. PMID:28150817

  12. Nonlinear photoacoustic spectroscopy of hemoglobin

    NASA Astrophysics Data System (ADS)

    Danielli, Amos; Maslov, Konstantin; Favazza, Christopher P.; Xia, Jun; Wang, Lihong V.

    2015-05-01

    As light intensity increases in photoacoustic imaging, the saturation of optical absorption and the temperature dependence of the thermal expansion coefficient result in a measurable nonlinear dependence of the photoacoustic (PA) signal on the excitation pulse fluence. Here, under controlled conditions, we investigate the intensity-dependent photoacoustic signals from oxygenated and deoxygenated hemoglobin at varied optical wavelengths and molecular concentrations. The wavelength and concentration dependencies of the nonlinear PA spectrum are found to be significantly greater in oxygenated hemoglobin than in deoxygenated hemoglobin. These effects are further influenced by the hemoglobin concentration. These nonlinear phenomena provide insights into applications of photoacoustics, such as measurements of average inter-molecular distances on a nm scale or with a tuned selection of wavelengths, a more accurate quantitative PA tomography.

  13. More Refined Experiments with Hemoglobin.

    ERIC Educational Resources Information Center

    Morin, Phillippe

    1985-01-01

    Discusses materials needed, procedures used, and typical results obtained for experiments designed to make a numerical stepwise study of the oxygenation of hemoglobin, myoglobin, and other oxygen carriers. (JN)

  14. Nonlinear photoacoustic spectroscopy of hemoglobin

    SciTech Connect

    Danielli, Amos; Maslov, Konstantin; Favazza, Christopher P.; Xia, Jun; Wang, Lihong V.

    2015-05-18

    As light intensity increases in photoacoustic imaging, the saturation of optical absorption and the temperature dependence of the thermal expansion coefficient result in a measurable nonlinear dependence of the photoacoustic (PA) signal on the excitation pulse fluence. Here, under controlled conditions, we investigate the intensity-dependent photoacoustic signals from oxygenated and deoxygenated hemoglobin at varied optical wavelengths and molecular concentrations. The wavelength and concentration dependencies of the nonlinear PA spectrum are found to be significantly greater in oxygenated hemoglobin than in deoxygenated hemoglobin. These effects are further influenced by the hemoglobin concentration. These nonlinear phenomena provide insights into applications of photoacoustics, such as measurements of average inter-molecular distances on a nm scale or with a tuned selection of wavelengths, a more accurate quantitative PA tomography.

  15. Quality of HbA1c Measurement in Trinidad and Tobago

    PubMed Central

    Rastogi, Maynika V.; Ladenson, Paul; Goldstein, David E.; Little, Randie R.

    2015-01-01

    Background: Monitoring of HbA1c is the standard of care to assess diabetes control. In Trinidad & Tobago (T&T) there are no existing data on the quality of HbA1c measurement. Our study examined the precision and accuracy of HbA1c testing in T&T. Methods: Sets of 10 samples containing blinded duplicates were shipped to laboratories in T&T. This exercise was repeated 6 months later. Precision and accuracy were estimated for each laboratory/method. Results: T&T methods included immunoassay, capillary electrophoresis, and boronate affinity binding. Most, but not all, laboratories demonstrated acceptable precision and accuracy. Conclusions: Continuous oversight of HbA1c testing (eg, through proficiency testing) in T&T is recommended. These results highlight the lack of oversight of HbA1c testing in some developing countries. PMID:26553021

  16. HbA(1c)--an analyte of increasing importance.

    PubMed

    Higgins, Trefor

    2012-09-01

    Since the incorporation in 1976 of HbA(1c) into a monitoring program of individuals with diabetes, this test has become the gold standard for assessment of glycemic control. Analytical methods have steadily improved in the past two decades, largely through the efforts of the National Glycohemoglobin Standardization program (NGSP). The new definition of HbA(1c) and the introduction of an analytically pure calibrator have increased the possibility for greater improvements in analytical performance. Controversies exist in the reporting of HbA(1c). The use of HbA(1c) has expanded beyond the use solely as a measure of glycemic control into a test for screening and diagnosing diabetes. With improvements in analytical performance, the effects of demographic factors such as age and ethnicity and clinical factors such as iron deficiency have been observed. In this review, the history, formation, analytical methods and parameters that affect HbA(1c) analysis are discussed.

  17. Rice ( Oryza) hemoglobins

    PubMed Central

    Arredondo-Peter, Raúl; Moran, Jose F.; Sarath, Gautam

    2014-01-01

    Hemoglobins (Hbs) corresponding to non-symbiotic (nsHb) and truncated (tHb) Hbs have been identified in rice ( Oryza). This review discusses the major findings from the current studies on rice Hbs. At the molecular level, a family of the nshb genes, consisting of hb1, hb2, hb3, hb4 and hb5, and a single copy of the thb gene exist in Oryza sativa var. indica and O. sativa var. japonica, Hb transcripts coexist in rice organs and Hb polypeptides exist in rice embryonic and vegetative organs and in the cytoplasm of differentiating cells. At the structural level, the crystal structure of rice Hb1 has been elucidated, and the structures of the other rice Hbs have been modeled. Kinetic analysis indicated that rice Hb1 and 2, and possibly rice Hb3 and 4, exhibit a very high affinity for O 2, whereas rice Hb5 and tHb possibly exhibit a low to moderate affinity for O 2. Based on the accumulated information on the properties of rice Hbs and data from the analysis of other plant and non-plant Hbs, it is likely that Hbs play a variety of roles in rice organs, including O 2-transport, O 2-sensing, NO-scavenging and redox-signaling. From an evolutionary perspective, an outline for the evolution of rice Hbs is available. Rice nshb and thb genes vertically evolved through different lineages, rice nsHbs evolved into clade I and clade II lineages and rice nshbs and thbs evolved under the effect of neutral selection. This review also reveals lacunae in our ability to completely understand rice Hbs. Primary lacunae are the absence of experimental information about the precise functions of rice Hbs, the properties of modeled rice Hbs and the cis-elements and trans-acting factors that regulate the expression of rice hb genes, and the partial understanding of the evolution of rice Hbs. PMID:25653837

  18. Rice ( Oryza) hemoglobins.

    PubMed

    Arredondo-Peter, Raúl; Moran, Jose F; Sarath, Gautam

    2014-01-01

    Hemoglobins (Hbs) corresponding to non-symbiotic (nsHb) and truncated (tHb) Hbs have been identified in rice ( Oryza). This review discusses the major findings from the current studies on rice Hbs. At the molecular level, a family of the nshb genes, consisting of hb1, hb2, hb3, hb4 and hb5, and a single copy of the thb gene exist in Oryza sativa var. indica and O. sativa var. japonica, Hb transcripts coexist in rice organs and Hb polypeptides exist in rice embryonic and vegetative organs and in the cytoplasm of differentiating cells. At the structural level, the crystal structure of rice Hb1 has been elucidated, and the structures of the other rice Hbs have been modeled. Kinetic analysis indicated that rice Hb1 and 2, and possibly rice Hb3 and 4, exhibit a very high affinity for O 2, whereas rice Hb5 and tHb possibly exhibit a low to moderate affinity for O 2. Based on the accumulated information on the properties of rice Hbs and data from the analysis of other plant and non-plant Hbs, it is likely that Hbs play a variety of roles in rice organs, including O 2-transport, O 2-sensing, NO-scavenging and redox-signaling. From an evolutionary perspective, an outline for the evolution of rice Hbs is available. Rice nshb and thb genes vertically evolved through different lineages, rice nsHbs evolved into clade I and clade II lineages and rice nshbs and thbs evolved under the effect of neutral selection. This review also reveals lacunae in our ability to completely understand rice Hbs. Primary lacunae are the absence of experimental information about the precise functions of rice Hbs, the properties of modeled rice Hbs and the cis-elements and trans-acting factors that regulate the expression of rice hb genes, and the partial understanding of the evolution of rice Hbs.

  19. Globin chain analysis: an important tool in phenotype study of hemoglobin disorders.

    PubMed

    Wajcman, Henri; Riou, Jean

    2009-12-01

    Phenotype studies still occupy a key position in the diagnosis of hemoglobin (Hb) disorders. An additional dimension to the methods for diagnosis of Hb disorders which are mostly based on difference in charge of the Hb molecules may be brought by studying some properties of the globin chains. Among the methods proposed, reversed-phase liquid-chromatography (RP-LC) reveals differences in hydrophobicity allowing to discriminate between variants displaying identical charges. Thus, abnormal Hbs responsible for hematological disorders, such as chronic hemolytic anemia, erythrocytosis, or thalassemia like presentation, but with a charge similar to HbA or to that of a common variant may be revealed. Also RP-LC, which discriminates between the two types of gamma chains, may be of interest for diagnosis of hereditary persistence of fetal hemoglobin (HPFH) or for suggesting a haplotype in the case of sickle cell anemia.

  20. Re-evaluation of glycated hemoglobin and glycated albumin with continuous glucose monitoring system as markers of glycemia in patients with liver cirrhosis

    PubMed Central

    Isoda, Hiroshi; Takahashi, Hirokazu; Eguchi, Yuichiro; Kojima, Motoyasu; Inoue, Kanako; Murayama, Kenichiro; Matsuda, Yayoi; Anzai, Keizo

    2017-01-01

    Liver cirrhosis (LC) is frequently accompanied by glucose intolerance. The present study was designed to determine whether glycated hemoglobin A1c (HbA1c) and glycated albumin (GA) were predictive markers of glycemia, as determined by a continuous glucose monitoring system (CGMS), in patients with LC. A total of 30 patients with LC, including 3, 19, 5, 2 and 1 with LC due to hepatitis B virus, hepatitis C virus, non-alcoholic steatohepatitis, alcohol and unknown causes, respectively, were assessed by CGMS. The average, maximum and minimum blood glucose (BG) levels were measured by CGMS, and correlated with HbA1c and GA. The average, maximum and minimum BG in these individuals were 142±38.7, 209.3±65.7 and 85.1±25.4 mg/dl, respectively. HbA1c was significantly correlated with average BG (r=0.447, P=0.015) and maximum BG (r=0.523, P=0.004). In addition, GA was significantly correlated with average BG (r=0.687, P<0.001) and maximum BG (r=0.648, P<0.001). Neither HbA1c nor GA was significantly correlated with minimum BG. Correlation analysis yielded formulas by which HbA1c and GA were predictive of average BG in individuals with LC: Average BG=19.2 × HbA1c (%) + 36.5 and average BG=6.6 × GA (%) + 13.0, respectively. In conclusion, HbA1c and GA showed significant correlations with average and maximum BG, as determined by CGMS. The derived formulas allow for estimates of average BG based on HbA1c and GA, and may contribute to the control of glycemia in patients with LC. PMID:28123707

  1. Health Coaching Reduces HbA1c in Type 2 Diabetic Patients From a Lower-Socioeconomic Status Community: A Randomized Controlled Trial

    PubMed Central

    Wayne, Noah; Perez, Daniel F; Kaplan, David M

    2015-01-01

    Background Adoptions of health behaviors are crucial for maintaining good health after type 2 diabetes mellitus (T2DM) diagnoses. However, adherence to glucoregulating behaviors like regular exercise and balanced diet can be challenging, especially for people living in lower-socioeconomic status (SES) communities. Providing cost-effective interventions that improve self-management is important for improving quality of life and the sustainability of health care systems. Objective To evaluate a health coach intervention with and without the use of mobile phones to support health behavior change in patients with type 2 diabetes. Methods In this noninferiority, pragmatic randomized controlled trial (RCT), patients from two primary care health centers in Toronto, Canada, with type 2 diabetes and a glycated hemoglobin/hemoglobin A1c (HbA1c) level of ≥7.3% (56.3 mmol/mol) were randomized to receive 6 months of health coaching with or without mobile phone monitoring support. We hypothesized that both approaches would result in significant HbA1c reductions, although health coaching with mobile phone monitoring would result in significantly larger effects. Participants were evaluated at baseline, 3 months, and 6 months. The primary outcome was the change in HbA1c from baseline to 6 months (difference between and within groups). Other outcomes included weight, waist circumference, body mass index (BMI), satisfaction with life, depression and anxiety (Hospital Anxiety and Depression Scale [HADS]), positive and negative affect (Positive and Negative Affect Schedule [PANAS]), and quality of life (Short Form Health Survey-12 [SF-12]). Results A total of 138 patients were randomized and 7 were excluded for a substudy; of the remaining 131, 67 were allocated to the intervention group and 64 to the control group. Primary outcome data were available for 97 participants (74.0%). While both groups reduced their HbA1c levels, there were no significant between-group differences in

  2. Hemoglobin Wayne Trait with Incidental Polycythemia.

    PubMed

    Ambelil, Manju; Nguyen, Nghia; Dasgupta, Amitava; Risin, Semyon; Wahed, Amer

    2017-01-01

    Hemoglobinopathies, caused by mutations in the globin genes, are one of the most common inherited disorders. Many of the hemoglobin variants can be identified by hemoglobin analysis using conventional electrophoresis and high performance liquid chromatography; however hemoglobin DNA analysis may be necessary in other cases for confirmation. Here, we report a case of a rare alpha chain hemoglobin variant, hemoglobin Wayne, in a 47-year-old man who presented with secondary polycythemia. Capillary zone electrophoresis and high performance liquid chromatography revealed a significant amount of a hemoglobin variant, which was further confirmed by hemoglobin DNA sequencing as hemoglobin Wayne. Since the patient was not homozygous for hemoglobin Wayne, which is associated with secondary polycythemia, the laboratory diagnosis in this case was critical in ruling out hemoglobinopathy as the etiology of his polycythemia.

  3. Aggregation of normal and sickle hemoglobin in high concentration phosphate buffer.

    PubMed

    Chen, Kejing; Ballas, Samir K; Hantgan, Roy R; Kim-Shapiro, Daniel B

    2004-12-01

    Sickle cell disease is caused by a mutant form of hemoglobin, hemoglobin S, that polymerizes under hypoxic conditions. The extent and mechanism of polymerization are thus the subject of many studies of the pathophysiology of the disease and potential treatment strategies. To facilitate such studies, a model system using high concentration phosphate buffer (1.5 M-1.8 M) has been developed. To properly interpret results from studies using this model it is important to understand the similarities and differences in hemoglobin S polymerization in the model compared to polymerization under physiological conditions. In this article, we show that hemoglobin S and normal adult hemoglobin, hemoglobin A, aggregate in high concentration phosphate buffer even when the concentration of hemoglobin is below the solubility defined for polymerization. This phenomenon was not observed using 0.05 M phosphate buffer or in another model system we studied that uses dextran to enhance polymerization. We have used static light scattering, dynamic light scattering, and differential interference contrast microscopy to confirm aggregation of deoxygenated and oxygenated hemoglobins below their solubility and have shown that this aggregation is not observable using turbidity measurements, a common technique for assessing polymerization. We have also shown that the aggregation increases with increasing temperature in the range of 15 degrees -37 degrees C and that it increases as the concentration of phosphate increases. These studies contribute to the working knowledge of how to properly apply studies of hemoglobin S polymerization that are conducted using the high phosphate model.

  4. Multi-ethnic differences in HbA1c, blood pressure, and low-density-lipid cholesterol control among South Africans living with type 2 diabetes, after a 4-year follow-up

    PubMed Central

    Pinchevsky, Yacob; Shukla, Varada J; Butkow, Neil; Chirwa, Tobias; Raal, Frederick

    2016-01-01

    Purpose Our study set out to examine if disparities in control of glycated hemoglobin (HbA1c), blood pressure (BP), and low-density-lipoprotein cholesterol (LDL-C) existed among an urban multi-ethnic cohort of South Africans, living with type 2 diabetes mellitus (T2DM). Patients and methods This longitudinal, retrospective study consisted of 261 men and women with previously diagnosed T2DM who attended Charlotte Maxeke Johannesburg Academic Hospital, South Africa across two time periods 2009 and 2013. Demographic and clinical data were extracted from consecutive medical records. The primary outcome was to determine achievements in HbA1c, BP, and LDL-C among ethnic groups using evidence-based goals. Results The mean age of the cohort was 64 (±10.6) years, females represented 55%, and the self-reported diabetes duration was 16 (±10.6) years as at 2013. Black Africans (42.9%, n=112 of 261) were more likely to reach the HbA1c target (<7%) and less likely to have had retinopathy, nephropathy, or cardiovascular disease. Over two-thirds of mixed-ancestry patients attained the BP target (<140/80 mmHg), while 90.2% of Caucasians achieved LDL-C goals (<2.5 mmol/L). Overall, across the ethnic groups studied, we found that HbA1c control deteriorated over time, although BP levels remained the same and LDL-C levels drastically improved. Conclusion There was poor control of HbA1c, BP, and LDL-C across all ethnic groups. Although a minority achieved recommended targets, some ethnic groups appeared to have worse control than others. Timely aggressive actions in particularly high-risk ethnic groups will prevent/delay the complications commonly associated with T2DM. PMID:27895508

  5. Effect of baseline HbA1c level on the development of diabetes by lifestyle intervention in primary healthcare settings: insights from subanalysis of the Japan Diabetes Prevention Program

    PubMed Central

    Sakane, Naoki; Sato, Juichi; Tsushita, Kazuyo; Tsujii, Satoru; Kotani, Kazuhiko; Tominaga, Makoto; Kawazu, Shoji; Sato, Yuzo; Usui, Takeshi; Kamae, Isao; Yoshida, Toshihide; Kiyohara, Yutaka; Sato, Shigeaki; Tsuzaki, Kokoro; Takahashi, Kaoru; Kuzuya, Hideshi

    2014-01-01

    Objectives To determine the effects of a lifestyle intervention on the development of type 2 diabetes mellitus (T2DM) among participants with impaired glucose tolerance (IGT), in particular in the subgroup with baseline glycated hemoglobin (HbA1c) levels ≥5.7%, in primary healthcare settings. Design Randomized controlled trial. Setting 32 healthcare centers in Japan. Participants Participants with IGT, aged 30–60 years, were randomly assigned to either an intensive lifestyle intervention group (ILG) or a usual care group (UCG). Interventions During the initial 6 months, participants in the ILG received four group sessions on healthy lifestyles by public health providers. An individual session was further conducted biannually during the 3 years. Participants in the UCG received usual care such as one group session on healthy lifestyles. Outcome measures The primary endpoint was the development of T2DM based on an oral glucose tolerance test. Results The mean follow-up period was 2.3 years. The annual incidence of T2DM were 2.7 and 5.1/100 person-years of follow-up in the ILG (n=145) and UCG (n=149), respectively. The cumulative incidence of T2DM was significantly lower in the ILG than in the UCG among participants with HbA1c levels ≥5.7% (log-rank=3.52, p=0.06; Breslow=4.05, p=0.04; Tarone-Ware=3.79, p=0.05), while this was not found among participants with HbA1c levels <5.7%. Conclusions Intensive lifestyle intervention in primary healthcare setting is effective in preventing the development of T2DM in IGT participants with HbA1c levels ≥5.7%, relative to those with HbA1c levels <5.7%. Trial registration number UMIN000003136. PMID:25452854

  6. Reactions of arsine with hemoglobin

    SciTech Connect

    Hatlelid, K.M.; Brailsford, C.; Carter, D.E.

    1996-02-09

    The mechanism of arsine (AsH{sub 3}) induced hemolysis was studied in vitro using isolated red blood cells (RBCs) from the rat or dog. AsH{sub 3}-induced hemolysis of dog red blood cells was completely blocked by carbon monoxide (CO) preincubation and was reduced by pure oxygen (O{sub 2}) compared to incubations in air. Since CO and O{sub 2} bind to heme and also reduced hemolysis, these results suggested a reaction between AsH{sub 3} and hemoglobin in the hemeligand binding pocket or with the heme iron. Further, sodium nitrite induction of methemoglobin (metHb) to 85% and 34% of total Hb in otherwise intact RBCs resulted in 56% and 16% decreases in hemolysis, respectively, after incubation for 4 h. This provided additional evidence for the involvement of hemoglobin in the AsH{sub 3}-induced hemolysis mechanism. Reactions between AsH{sub 3} and hemoglobin were studied in solutions of purified dog hemoglobin. Spectrophotometric studies of the reaction of AsH{sub 3} with various purified hemoglobin species revealed that AsH{sub 3} reacted with HbO{sub 2} to produce metHb and, eventually, degraded Hb characterized by gross precipitation of the protein. AsH{sub 3} did not alter the spectrum of deoxyHb and did not cause degradation of metHb in oxygen, but bound to and reduced metHb in the absence of oxygen. These data indicate that a reaction of AsH{sub 3} with oxygenated hemoglobin, HbO{sub 2}, may lead to hemolysis, but there are reactions between AsH{sub 3} and metHb that may not be directly involved in the hemolytic process. 17 refs., 6 figs.

  7. The Associations Between Smoking Habits and Serum Triglyceride or Hemoglobin A1c Levels Differ According to Visceral Fat Accumulation

    PubMed Central

    Koda, Michiko; Kitamura, Itsuko; Okura, Tomohiro; Otsuka, Rei; Ando, Fujiko; Shimokata, Hiroshi

    2016-01-01

    Background Whether smokers and former smokers have worse lipid profiles or glucose levels than non-smokers remains unclear. Methods The subjects were 1152 Japanese males aged 42 to 81 years. The subjects were divided according to their smoking habits (nonsmokers, former smokers, and current smokers) and their visceral fat area (VFA) (<100 cm2 and ≥100 cm2). Results The serum triglyceride (TG) levels of 835 males were assessed. In the VFA ≥100 cm2 group, a significantly greater proportion of current smokers (47.3%) exhibited TG levels of ≥150 mg/dL compared with former smokers (36.4%) and non-smokers (18.8%). The difference in TG level distribution between former smokers and non-smokers was also significant. However, among the subjects with VFA of <100 cm2, the TG levels of the three smoking habit groups did not differ. The serum hemoglobin A1c (HbA1c) levels of 877 males were also assessed. In the VFA <100 cm2 group, significantly higher proportions of current smokers (17.9%) and former smokers (14.9%) demonstrated HbA1c levels of ≥5.6% compared with non-smokers (6.3%). In contrast, in the VFA ≥100 cm2 group, significantly fewer former smokers displayed HbA1c levels of ≥5.6% compared with non-smokers and current smokers. Furthermore, the interaction between smoking habits and VFA was associated with the subjects’ TG and HbA1c concentrations, and the associations of TG and HbA1c concentrations and smoking habits varied according to VFA. Conclusions Both smoking habits and VFA exhibited associations with TG and HbA1c concentrations. The associations between smoking habits and these parameters differed according to VFA. PMID:26616395

  8. Comparative study of glycated hemoglobin by ion exchange chromatography and affinity binding nycocard reader in type 2 diabetes mellitus.

    PubMed

    Gautam, N; Dubey, R K; Jayan, A; Nepaune, Y; Padmavathi, P; Chaudhary, S; Jha, S K; Sinha, A K

    2014-12-01

    The aim of this study was to compare the level of glycated hemoglobin (HbA1c) in type 2 Diabetes Mellitus (DM) patients by two different methods namely Ion Exchange Chromatography and Affinity Binding Nycocard Reader. This is a cross-sectional study conducted on confirmed type 2 diabetes mellitus patients (n = 100) who visited Out Patients Department of the Universal College of Medical Sciences Teaching hospital, Bhairahawa, Nepal from November 2012 to March 2013. The diagnosis of diabetes mellitus was done on the basis of their fasting (164.46 ± 45.33 mg/dl) and random (187.93 ± 78.02 mg/dl) serum glucose level along with clinical history highly suggestive of type 2 DM. The HbA1c values of (7.8 ± 1.9%) and (8.0 ± 2.2%) were found in DM patients as estimated by those two different methods respectively. The highest frequency was observed in HbA1c > 8.0% indicating maximum cases were under very poor glycemic control. However, there were no significant differences observed in HbA1c value showing both methods are comparable in nature and can be used in lab for ease of estimation. The significant raised in HbA1c indicates complications associated with DM and monitoring of therapy become hard for those patients. Despite having standard reference method for HbA1c determination, the availability of report at the time of the patient visit can be made easy by using Nycocard Reader and Ion Exchange Chromatography techniques without any delay in communicating glycemic control, clinical decision-making and changes in treatment regimen.

  9. An indirect comparison of HbA1c treatment effect with albiglutide and exenatide 2.0 mg QW using the Bucher method

    PubMed Central

    Martin, Alan A; Parks, Daniel

    2016-01-01

    No head-to-head comparisons exist between once-weekly (QW) glucagon-like peptide-1 receptor agonists; accordingly, this indirect comparison was conducted to evaluate the comparative efficacy of QW albiglutide vs QW exenatide. Following a systematic literature search, it was determined that HARMONY 7 and DURATION 6, Phase III trials for albiglutide and exenatide, respectively, were similar in study design and baseline characteristics and included a common comparator arm, making them suitable for an indirect comparison using the Bucher method. The primary endpoint of change from baseline in glycated hemoglobin (HbA1c) with albiglutide 50 mg QW and exenatide 2.0 mg QW was compared and tested for noninferiority. The indirect comparison showed a treatment difference of 0.0% (95% confidence interval: −0.189% to 0.189%) in mean change in HbA1c from baseline, and albiglutide 50 mg was noninferior to exenatide 2.0 mg QW at the noninferiority margin of 0.3%. In the absence of a head-to-head trial, these results can be used in pharmacoeconomic analysis and to inform health technology assessment and clinical decision making. PMID:27274297

  10. C-Peptide Level in Fasting Plasma and Pooled Urine Predicts HbA1c after Hospitalization in Patients with Type 2 Diabetes Mellitus.

    PubMed

    Sonoda, Remi; Tanaka, Kentaro; Kikuchi, Takako; Onishi, Yukiko; Takao, Toshiko; Tahara, Tazu; Yoshida, Yoko; Suzawa, Naoki; Kawazu, Shoji; Iwamoto, Yasuhiko; Kushiyama, Akifumi

    2016-01-01

    In this study, we investigate how measures of insulin secretion and other clinical information affect long-term glycemic control in patients with type 2 diabetes mellitus. Between October 2012 and June 2014, we monitored 202 diabetes patients who were admitted to the hospital of Asahi Life Foundation for glycemic control, as well as for training and education in diabetes management. We measured glycated hemoglobin (HbA1c) six months after discharge to assess disease management. In univariate analysis, fasting plasma C-peptide immunoreactivity (F-CPR) and pooled urine CPR (U-CPR) were significantly associated with HbA1c, in contrast to ΔCPR and C-peptide index (CPI). This association was strongly independent of most other patient variables. In exploratory factor analysis, five underlying factors, namely insulin resistance, aging, sex differences, insulin secretion, and glycemic control, represented patient characteristics. In particular, insulin secretion and resistance strongly influenced F-CPR, while insulin secretion affected U-CPR. In conclusion, the data indicate that among patients with type 2 diabetes mellitus, F-CPR and U-CPR may predict improved glycemic control six months after hospitalization.

  11. The Relationship Between Vegetables and Fruits Intake and Glycosylated Hemoglobin Values, Lipids Profiles and Nitrogen Status in Type II Inactive Diabetic Patients

    PubMed Central

    Tabesh, Marjan; Hariri, Mitra; Askari, Gholamreza; Ghiasvand, Reza; Tabesh, Maryam; Heydari, Asieh; Darvishi, Leila; Khorvash, Fariba

    2013-01-01

    Background: The prevalence of obesity and associated chronic disease such as diabetes is rapidly increasing in all part of the world. The World Health Organization has predicted that between 1997 and 2025 the number of diabetic patients will increase from 143 million to about 300 million. In diabetic patients, oxidative stress leads to non-enzymatic glycosylation of proteins such as hemoglobin and albumin, these proteins can play a significant role in pathogenesis of diabetes and development of chronic disorders in diabetic patients. Antioxidant nutrients can reduce the chronic disorders and complications of diabetes by inhibiting the oxidative reactions. Some important antioxidant such as vitamin A, vitamin C, vitamin E and selenium occur in vegetables and fruits. Our objective of this study was investigation of the relationship between vegetables and fruits intake ssand glycosylated hemoglobin (HbA1C) values in diabetic patients. Methods: One hundred and five diabetic patients participated in this cross-sectional study. The patients were referred to health center in Khomeini shahr. Glycosylated hemoglobin (HbA1C) values were measured by chromatography method. Data on dietary intake and vegetables and fruits consumption were obtained from validated food frequency questionnaires. Results: The unadjusted mean glycosylated hemoglobin (HbA1C) is significantly associated with the amount of vegetables and fruits intake (P = 0.014), but the relationship between consumption of fruits and HbA1C is not significant and the relationship between consumption of vegetables and HbA1C was roughly significant (P = 0.049). There were no significant relationship between vegetables and fruits intake and lipids profiles, BUN/creatinine and 24 h urinary protein (P > 0.05). Conclusions: Intake of vegetables and fruits may reduce the glycosylated hemoglobin, therefore choosing the appropriate diet with high fruits and vegetables may help to develop antioxidant defense and reduce the HbA1C

  12. Hemoglobin glycation index as a useful predictor of therapeutic responses to dipeptidyl peptidase-4 inhibitors in patients with type 2 diabetes

    PubMed Central

    Chen, Yu-Wei; Wang, Jun-Sing; Sheu, Wayne H-H; Lin, Shih-Yi; Lee, I-Te; Song, Yuh-Min; Fu, Chia-Po; Lee, Chia-Lin

    2017-01-01

    Introduction A high hemoglobin glycation index (HGI) and glycated hemoglobin (HbA1c) level are associated with greater inflammatory status, and dipeptidyl peptidase-4 (DPP-4) inhibitors can suppress inflammation. We aimed to evaluate the relationship between HGI and the therapeutic effect of DPP-4 inhibitors. Methods This retrospective cohort study followed 468 patients with type 2 diabetes receiving DPP-4 inhibitor treatment for 1 year. Estimated HbA1c was calculated using a linear regression equation derived from another 2969 randomly extracted patients with type 2 diabetes based on fasting plasma glucose (FPG) level. The subjects were divided into two groups based on HGI (HGI = observed HbA1c - estimated HbA1c). Mixed model repeated measures were used to compare the treatment efficacy after 1 year in patients with a low (HGI<0, n = 199) and high HGI (HGI≧0, n = 269). Results There were no significant group differences in mean changes of FPG after 1 year (-12.8 and -13.4 mg/dL in the low and high HGI groups, respectively). However, the patients with a high HGI had a significantly greater reduction in HbA1c from baseline compared to those with a low HGI (-1.9 versus -0.3% [-20.8 versus -3.3 mmol/mol]). Improvements in glycemic control were statistically significantly associated with the tested DPP-4 inhibitors in the high HGI group (-2.4, -1.4, -1.2 and -2.2% [-26.2, -15.3, -13.1 and -24.0 mmol/mol] for vildagliptin, linagliptin, saxagliptin and sitagliptin, respectively) but not in the low HGI group. Conclusions The HGI index derived from FPG and HbA1c may be able to identify who will have a better response to DPP-4 inhibitors. PMID:28182722

  13. A history of HbA1c through Clinical Chemistry and Laboratory Medicine.

    PubMed

    Gillery, Philippe

    2013-01-01

    HbA(1c) was discovered in the late 1960s and its use as marker of glycemic control has gradually increased over the course of the last four decades. Recognized as the gold standard of diabetic survey, this parameter was successfully implemented in clinical practice in the 1970s and 1980s and internationally standardized in the 1990s and 2000s. The use of standardized and well-controlled methods, with well-defined performance criteria, has recently opened new directions for HbA(1c) use in patient care, e.g., for diabetes diagnosis. Many reports devoted to HbA1c have been published in Clinical Chemistry and Laboratory Medicine (CCLM) journal. This review reminds the major steps of HbA(1c) history, with a special emphasis on the contribution of CCLM in this field.

  14. Detection of HbA(1c) by boronate affinity immunoassay using bacterial magnetic particles.

    PubMed

    Tanaka, T; Matsunaga, T

    2001-12-01

    We have developed a boronate affinity immunoassay system using m-aminophenylboronic acid (mAPB) coupling to bacterial magnetic particles (BMPs). Homobifunctional crosslinker, Bis-(succcimidyl)suberate (BS3), was employed for preparation of mAPB-BMPs conjugates (mAPB-BMPs). Quantities of HbA(1c) on mAPB-BMPs were evaluated based on luminescence from alkaline phosphatase-conjugated anti-Hb antibody (ALP-antibody) binding to HbA(1c) on the BMP surface. The binding of HbA(1c) to mAPB-BMPs occurred gradually and was almost completed within 10 mm. The coupling reaction is enhanced due to static electric interaction between the positive charges on HbA(1c) and negative charges on BMPs. The amount of HbA(1c) binding to mAPB-BMPs increased with increasing sodium chloride concentrations in the range of 0-100 mM. However, the amount of Hb binding to mAPB-BMPs also increased in high concentration of sodium chloride. The Hb binding to mAPB-BMPs was detached from mAPB-BMPs when Hb-mAPB-BMPs were washed with low salt buffer. This indicates that Hb is nonspecifically adsorbed onto the surface of mAPB-BMPs in high concentration of sodium chloride. These results suggest that selective separation of HbA(1c) using mAPB-BMPs can be achieved with these conditions. A dose-response curve was obtained between luminescence intensity and HbA(1c) concentration using a fully automated boronate affinity immunoassay. A linear relationship between luminescence intensity and HbA(1c) concentration was obtained in the range of 10-10(4) ng/ml.

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

    PubMed

    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%, P<0.01). We have shown for the first time that aldimine (LX1c) formation reaction 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.

  16. Distribution of hemoglobin phenotypes in four different districts of Porto Velho, Rondônia, Brazil.

    PubMed

    Andrade-Casseb, A; Krauze, A; Lafontaine, R M; Tada, M S; Silva, W A; Simões, A L; Engracia, V

    2008-10-01

    Hemoglobin profile studies have been carried out in four samples from different districts of Porto Velho (Rondônia State) in the western Amazonian region of Brazil: Candelária, Bate Estaca, Hemeron (at the State Blood Bank), and São Carlos. Samples from 337 unrelated individuals were collected during medical and paramedical team visits by professionals from the Instituto de Pesquisa em Patologia Tropical and the Centro de Pesquisa em Patologias Tropicais (both research institutes in tropical diseases). The aim of this study is to assess the frequency of alleles in the hemoglobin system, mainly alleles HB*A, *S, and *E. The overall phenotype frequencies were HB A,S = 0.025, HB A,E = 0.006, and HB A,A = 0.969. Samples from the blood bank subjects and samples from the homogeneous areas of São Carlos and Candelária plus Bate Estaca have a chi-square of heterogeneity of 6.383 (p = 0.041) and 8.406 (p = 0.015), respectively. The allele frequencies (HB*A = 0.984, HB*S = 0.012, and HB*E = 0.003) do not significantly differ from frequencies found in other Brazilian regions.

  17. Hemoglobin in a coacervate system.

    PubMed

    Ecanow, J; Ecanow, D; Ecanow, B

    1990-01-01

    Hemoglobin dissolved in a coacervate system shows the properties of a resuscitation fluid. In the coacervate system used, the equilibrium phase was the colloid rich phase. We propose a new definition of the coacervate phase to be that phase in a coacervate system which is most dissimilar to water in its physical chemical properties.

  18. Fiber in Diet Is Associated with Improvement of Glycated Hemoglobin and Lipid Profile in Mexican Patients with Type 2 Diabetes

    PubMed Central

    Velázquez-López, Lubia; Muñoz-Torres, Abril Violeta; García-Peña, Carmen; López-Alarcón, Mardia; Islas-Andrade, Sergio; Escobedo-de la Peña, Jorge

    2016-01-01

    Objective. To assess the association of dietary fiber on current everyday diet and other dietary components with glycated hemoglobin levels (HbA1c), glucose, lipids profile, and body weight body weight, in patients with type 2 diabetes. Methods. A cross-sectional survey of 395 patients with type 2 diabetes was performed. HbA1c, fasting glucose, triglycerides, and lipids profile were measured. Weight, waist circumference, blood pressure, and body composition were measured. Everyday diet with a semiquantitative food frequency questionnaire was evaluated. ANOVA, Kruskal-Wallis, chi-square tests and multivariate logistic regression were used in statistical analysis. Results. Higher fiber intake was associated with a low HbA1c, high HDL-c levels, low weight, and waist circumference. The highest tertile of calories consumption was associated with a higher fasting glucose level and weight. The highest tertile of carbohydrate consumption was associated with a lower weight. The lowest tertile of total fat and saturated fat was associated with the highest tertile of HDL-c levels, and lower saturated fat intake was associated with lower weight (p < 0.05). Conclusions. A higher content of fiber in the diet reduces HbA1c and triglycerides, while improving HDL-c levels. Increasing fiber consumption while lowering calorie consumption seems to be an appropriate strategy to reduce body weight and promote blood glucose control. PMID:27144178

  19. Radiation-induced changes in the optical properties of hemoglobin molecule.

    PubMed

    Selim, Nabila S; El-Marakby, Seham M

    2010-06-01

    Adult male Albino rats were exposed to different doses of gamma radiation from Cs-137 source. Hemoglobin samples were analyzed 24 h after irradiation. The UV-visible spectrum of hemoglobin molecule was measured in the range 200-700 nm. The overall spectrum of the hemoglobin molecule showed hypochromicity that increased with dose increase. To investigate the effect of radiation on the hemoglobin molecule, different parameters of the spectrum were calculated: molar absorption coefficient, absorption cross-section, transition dipole moment, dipole length, the optical energy gap and activation energy for each characteristic peak. The obtained results revealed that the radiation effect can induce rearrangement of the transition dipole moments and change molecular energy levels of the hemoglobin molecule.

  20. Radiation-induced changes in the optical properties of hemoglobin molecule

    NASA Astrophysics Data System (ADS)

    Selim, Nabila S.; El-Marakby, Seham M.

    2010-06-01

    Adult male Albino rats were exposed to different doses of gamma radiation from Cs-137 source. Hemoglobin samples were analyzed 24 h after irradiation. The UV-visible spectrum of hemoglobin molecule was measured in the range 200-700 nm. The overall spectrum of the hemoglobin molecule showed hypochromicity that increased with dose increase. To investigate the effect of radiation on the hemoglobin molecule, different parameters of the spectrum were calculated: molar absorption coefficient, absorption cross-section, transition dipole moment, dipole length, the optical energy gap and activation energy for each characteristic peak. The obtained results revealed that the radiation effect can induce rearrangement of the transition dipole moments and change molecular energy levels of the hemoglobin molecule.

  1. Recombinant Hemoglobins as Artificial Oxygen Carriers

    PubMed Central

    Fronticelli, Clara; Koehler, Raymond C.; Brinigar, William S.

    2008-01-01

    This paper describes the approaches we have taken to construct a) mutant hemoglobins with different oxygen affinities, and b) mutant hemoglobins and myoglobins that polymerize to high molecular weight aggregates in an effort to prevent extravasation and the associated vasoactivity. In vivo testing indicates that exchange transfusion of polymeric hemoglobins in mice does not result in vasoactivity and that polymeric hemoglobins are effective oxygen carriers to ischemic tissues irrespective of their oxygen affinity and cooperativity. PMID:17364470

  2. Carboxyalkylated Hemoglobin as a Potential Blood Substitute

    DTIC Science & Technology

    1989-09-20

    chromatography to remove minor and glycosylated hemoglobin components. Carbox) methylation Reaction - Many of the procedures have been described in our early...hemoglobin by peptide mapping after treatment with radiolabeled methyl acetyl phosphate. These binding sites are Met-l(3) and Lys-81(f) for liganded...ABSTRACT (Continue on reverse if necesary andia entify by block number) Carbox,, methylated hemoglobin is more stable than oxy hemoglobin during some

  3. DPP-4 inhibitor treatment: β-cell response but not HbA1c reduction is dependent on the duration of diabetes

    PubMed Central

    Kozlovski, Plamen; Bhosekar, Vaishali; Foley, James E

    2017-01-01

    Introduction Dipeptidyl peptidase-4 (DPP-4) inhibitors reduce hyperglycemia in patients with type 2 diabetes mellitus (T2DM) by enhancing insulin and suppressing glucagon secretion. Since T2DM is associated with progressive loss of β-cell function, we hypothesized that the DPP-4 inhibitor action to improve β-cell function would be attenuated with longer duration of T2DM. Methods Data from six randomized, placebo-controlled trials of 24 weeks duration, where β-cell response to vildagliptin 50 mg twice daily was assessed, were pooled. In each study, the insulin secretory rate relative to glucose (ISR/G 0–2h) during glucose load (standard meal or oral glucose tolerance test) was assessed at baseline and end of study. The mean placebo-subtracted difference (PSD) in the change in ISR/G 0–2h from baseline for each study was evaluated as a function of age, duration of T2DM, baseline ISR/G 0–2h, glycated hemoglobin (HbA1c), fasting plasma glucose, body mass index, and mean PSD in the change in HbA1c from baseline, using univariate model. Results There was a strong negative association between the PSD in the change from baseline in ISR/G 0–2h and duration of T2DM (r= −0.89, p<0.02). However, there was no association between the PSD in the change from baseline in ISR/G 0–2h and the PSD in the change from baseline in HbA1c (r=0.33, p=0.52). None of the other characteristics were significantly associated with mean PSD change in ISR/G 0–2h. Conclusion These findings indicate that the response of the β-cell, but not the HbA1c reduction, with vildagliptin is dependent on duration of T2DM. Further, it can be speculated that glucagon suppression may become the predominant mechanism via which glycemic control is improved when treatment with a DPP-4 inhibitor, such as vildagliptin, is initiated late in the natural course of T2DM.

  4. Fabrication of electrochemical interface based on boronic acid-modified pyrroloquinoline quinine/reduced graphene oxide composites for voltammetric determination of glycated hemoglobin.

    PubMed

    Zhou, Yanli; Dong, Hui; Liu, Lantao; Hao, Yuanqiang; Chang, Zhu; Xu, Maotian

    2015-02-15

    A voltammetric sensor for determination of glycated hemoglobin (HbA1c) was developed based on the composites of phenylboronic acid-modified pyrroloquinoline quinine (PBA-PQQ) and reduced graphene oxide. After the electrodeposition of reduced graphene oxide (ERGO) on the glassy carbon (GC) electrode, PQQ multilayer was decorated on the surface of the ERGO/GC electrode via potential cycling. Further modification with PBA would lead to the formation of the working electrode, namely PBA-PQQ/ERGO/GC electrode. PQQ on the electrode exhibited a quasi-reversible electrode process with 2-electron transfer and 2-proton participation, and the electron transfer efficiency was further enhanced by the introduction of ERGO layer. The complexation of PBA with HbA1c through specific boronic acid-diol recognition could cause the change of the oxidation peak current of PQQ on the electrode, which was utilized for HbA1c detection. Under the optimized conditions, the PBA-PQQ/ERGO/GC electrode provided high selectivity and high sensitivity for HbA1c detection with a linear range of 9.4-65.8 μg mL(-1) and a low detection limit of 1.25 μg mL(-1). The fabricated sensor was also successfully applied to determine the percentages of HbA1c in whole blood of healthy individuals.

  5. Burden of Diabetes and First Evidence for the Utility of HbA1c for Diagnosis and Detection of Diabetes in Urban Black South Africans: The Durban Diabetes Study

    PubMed Central

    Hird, Thomas R.; Pirie, Fraser J.; Esterhuizen, Tonya M.; O’Leary, Brian; McCarthy, Mark I.; Young, Elizabeth H.; Sandhu, Manjinder S.; Motala, Ayesha A.

    2016-01-01

    Objective Glycated haemoglobin (HbA1c) is recommended as an additional tool to glucose-based measures (fasting plasma glucose [FPG] and 2-hour plasma glucose [2PG] during oral glucose tolerance test [OGTT]) for the diagnosis of diabetes; however, its use in sub-Saharan African populations is not established. We assessed prevalence estimates and the diagnosis and detection of diabetes based on OGTT, FPG, and HbA1c in an urban black South African population. Research Design and Methods We conducted a population-based cross-sectional survey using multistage cluster sampling of adults aged ≥18 years in Durban (eThekwini municipality), KwaZulu-Natal. All participants had a 75-g OGTT and HbA1c measurements. Receiver operating characteristic (ROC) analysis was used to assess the overall diagnostic accuracy of HbA1c, using OGTT as the reference, and to determine optimal HbA1c cut-offs. Results Among 1190 participants (851 women, 92.6% response rate), the age-standardised prevalence of diabetes was 12.9% based on OGTT, 11.9% based on FPG, and 13.1% based on HbA1c. In participants without a previous history of diabetes (n = 1077), using OGTT as the reference, an HbA1c ≥48 mmol/mol (6.5%) detected diabetes with 70.3% sensitivity (95%CI 52.7–87.8) and 98.7% specificity (95%CI 97.9–99.4) (AUC 0.94 [95%CI 0.89–1.00]). Additional analyses suggested the optimal HbA1c cut-off for detection of diabetes in this population was 42 mmol/mol (6.0%) (sensitivity 89.2% [95%CI 78.6–99.8], specificity 92.0% [95%CI: 90.3–93.7]). Conclusions In an urban black South African population, we found a high prevalence of diabetes and provide the first evidence for the utility of HbA1c for the diagnosis and detection of diabetes in black Africans in sub-Saharan Africa. PMID:27560687

  6. Blood Test: Hemoglobin A1C

    MedlinePlus

    ... few minutes. previous continue What to Expect Either method (finger or heel sticking or vein withdrawal) of ... that since labs and offices may use different methods to measure HbA1c, the range of normal values ...

  7. Effects of Sleep Disorders on Hemoglobin A1c Levels in Type 2 Diabetic Patients

    PubMed Central

    Keskin, Ahmet; Ünalacak, Murat; Bilge, Uğur; Yildiz, Pinar; Güler, Seda; Selçuk, Engin Burak; Bilgin, Muzaffer

    2015-01-01

    Background: Studies have reported the presence of sleep disorders in approximately 50–70% of diabetic patients, and these may contribute to poor glycemic control, diabetic neuropathy, and overnight hypoglycemia. The aim of this study was to determine the frequency of sleep disorders in diabetic patients, and to investigate possible relationships between scores of these sleep disorders and obstructive sleep apnea syndrome (OSAS) and diabetic parameters (fasting blood glucose, glycated hemoglobin A1c [HbA1c], and lipid levels). Methods: We used the Berlin questionnaire (BQ) for OSAS, the Epworth Sleepiness Scale (ESS), and the Pittsburgh Sleep Quality Index (PSQI) to determine the frequency of sleep disorders and their possible relationships with fasting blood glucose, HbA1c, and lipid levels. Results: The study included 585 type 2 diabetic patients admitted to family medicine clinics between October and December 2014. Sleep, sleep quality, and sleep scores were used as the dependent variables in the analysis. The ESS scores showed that 54.40% of patients experienced excessive daytime sleepiness, and according to the PSQI, 64.30% experienced poor-quality sleep. The BQ results indicated that 50.20% of patients were at high-risk of OSAS. HbA1c levels correlated significantly with the ESS and PSQI results (r = 0.23, P < 0.001 and r = 0.14, P = 0.001, respectively), and were significantly higher in those with high-risk of OSAS as defined by the BQ (P < 0.001). These results showed that HbA1c levels were related to sleep disorders. Conclusions: Sleep disorders are common in diabetic patients and negatively affect the control of diabetes. Conversely, poor diabetes control is an important factor disturbing sleep quality. Addressing sleep disturbances in patients who have difficulty controlling their blood glucose has dual benefits: Preventing diabetic complications caused by sleep disturbance and improving diabetes control. PMID:26668142

  8. The amino acid sequence of Canada goose (Branta canadensis) and mute swan (Cygnus olor) hemoglobins. Two different species with identical beta-chains.

    PubMed

    Oberthür, W; Godovac-Zimmermann, J; Braunitzer, G; Wiesner, H

    1982-08-01

    The amino acid sequences of the alpha- and beta-chains from the major hemoglobin component (HbA) of Canada goose (Branta canadensis) and mute swan (Cygnus olor) are given. The alpha-chains are of the alpha A-type, since alpha D-type was expressed but only found in low concentrations. By homologous comparison, greylag goose hemoglobin (Anser anser) and Canada goose hemoglobin alpha-chains differ by two exchanges, and beta-chains by three exchanges. A valine substitution for threonine was found at position alpha 34 (B15). This exchange is a result of a two point mutation. Thus, there are three nucleotide mutations in alpha-chains, as in beta-chains. Substitutions in positions alpha 34 (B15) and beta 125 (H3) have modified intersubunit contacts (alpha 1 beta 1-contacts). A comparison of mute swan hemoglobin with greylag goose hemoglobin shows four exchanges in alpha-chains and three in beta-chains. Canada goose and mute swan have identical beta-chains, while alpha-chains differ in two amino acids. One of these exchanges is implicated in one of the alpha 1 beta 1-contact points (alpha 34) where isoleucine substitution for valine was found. Comparison of hemoglobins from different species in the same tribe (Anserini) shows a high homology between Canada goose and mute swan hemoglobins.

  9. Factor Analysis of Changes in Hemoglobin A1c After 12 Months of Sitagliptin Therapy in Patients With Type 2 Diabetes

    PubMed Central

    Yuasa, Shouhei; Sato, Kazuyoshi; Takai, Masahiko; Ishikawa, Masashi; Umezawa, Shinichi; Kubota, Akira; Maeda, Hajime; Kanamori, Akira; Miyakawa, Masaaki; Tanaka, Yasushi; Terauchi, Yasuo; Matsuba, Ikuro

    2016-01-01

    Background Sitagliptin, a dipeptidyl peptidase-4 inhibitor, is an effective oral antidiabetic agent as both monotherapy and when combined with insulin. Data from three observational studies performed in patients with type 2 diabetes receiving sitagliptin therapy in the routine clinical setting were integrated to conduct factor analysis of the changes in hemoglobin A1c (HbA1c), body weight, and estimated glomerular filtration rate (eGFR) over 12 months. Methods Among patients with type 2 diabetes attending medical institutions affiliated with Kanagawa Physicians Association, those using sitagliptin were followed for 1 year. In the ASSET-K and ASSIST-K studies, patients were managed by diabetologists, while they were managed by non-diabetologists in the ATTEST-K study. Patients were not administered insulin in ASSET-K, whereas insulin was administered in ASSIST-K. HbA1c (National Glycohemoglobin Standardization Program), blood glucose (fasting/postprandial), body weight, and renal function (serum creatinine and eGFR) were the efficacy endpoints. Factor analysis was performed by analysis of variance using the magnitude of the change in HbA1c, body weight, and eGFR after 12 months of sitagliptin therapy as response variables, and the study, sex, and age as explanatory variables. Results Of 1,327 patients registered in ASSET-K (diabetologists/without insulin), 1,167 patients in ASSIST-K (diabetologists/with insulin), and 530 patients in ATTEST-K (non-diabetologists), statistical analysis was carried out on 1,074, 854, and 411 patients, respectively. There were significant inter-study differences in patient characteristics (complications, duration of diabetes, and baseline HbA1c), the sitagliptin dose, and the use of other antidiabetic agents. HbA1c decreased significantly in all three studies. According to factor analysis, the magnitude of the change in HbA1c over 12 months showed significant inter-study differences and was also significantly influenced by the age

  10. Serum glycated hemoglobin level as a predictor of atrial fibrillation: A systematic review with meta-analysis and meta-regression

    PubMed Central

    Qi, Wenwei; Zhang, Nixiao; Korantzopoulos, Panagiotis; Letsas, Konstantinos P.; Cheng, Min; Di, Fusheng; Tse, Gary; Liu, Tong; Li, Guangping

    2017-01-01

    Background and Aim Glycated hemoglobin (HbA1c) is a long-term measure of glucose control. Although recent studies demonstrated a potential association between HbA1c levels and the risk of atrial fibrillation (AF), the results have been inconsistent. The aim of this meta-analysis is to evaluate the utility of HbA1c level in predicting AF. Methods PubMed and the Cochrane Library databases were searched for relevant studies up to March 2016. Prospective cohort studies and retrospective case-control studies were included. Relative risk (RR) or odds ratio (OR) with 95% confidence intervals (CIs) of AF development were determined for different HbA1c levels. The random effect model was conducted according to the test of heterogeneity among studies. Subgroup analyses and meta-regression models were carried out to identify potential sources of heterogeneity. Results Eight prospective cohort studies with 102,006 participants and 6 retrospective case-control studies with 57,669 patients were finally included in the meta-analysis. In the primary meta-analysis, HbA1c levels were not associated with an increased risk of AF whether as a continuous (RR, 1.06; 95% CI, 0.96–1.18) or categorical variable (RR, 0.99; 95% CI, 0.83–1.18). Nevertheless, prospective studies showed about 10% increased risk of AF with elevated HbA1c levels both as a continuous (RR, 1.11; 95% CI, 1.06–1.16) and as a categorical variable (RR, 1.09; 95% CI, 1.00–1.18). In subgroup analyses, pooled results from studies with longer follow-up durations, published after 2012, aged < 63 years, with exclusion of cardiac surgery patients demonstrated an increased risk of AF for every 1% increase in HbA1c levels, while studies conducted in the United States with longer follow-up (more than 96 months), larger sample size and higher quality score (≥6) showed an increased risk of AF for higher HbA1c level as a categorical variable. Conclusions Elevated serum HbA1c levels may be associated with an increased risk

  11. Stability study for magnetic reagent assaying Hb and HbA1c

    NASA Astrophysics Data System (ADS)

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

    2013-01-01

    Reagents for magnetically labeled immunoassay on human Hb and human HbA1c have been synthesized. The reagents consist of Fe3O4 magnetic particles biofunctionalized with antibodies against Hb and HbA1c. It has been demonstrated that the reagents can be applied to quantitatively detect Hb and HbA1c by using immunomagnetic reduction assay. In addition to characterizing the assay properties, such as the standard curve and the low-detection limit, the stability of reagents is investigated. To do this, the temporal dependence of particle sizes and the bio-activity of reagents are monitored. The results show that the reagents are highly stable when stored at 2-8 °C. This means that the reagents synthesized in this work are promising for practical applications.

  12. Development of an electrochemical immunosensor for the detection of HbA1c in serum.

    PubMed

    Liu, Guozhen; Khor, Sook Mei; Iyengar, Sridhar G; Gooding, J Justin

    2012-02-21

    An electrochemical immuno-biosensor for detecting glycosylated haemoglobin (HbA1c) is reported based on glassy carbon (GC) electrodes with a mixed layer of an oligo(phenylethynylene) molecular wire (MW) and an oligo(ethylene glycol) (OEG). The mixed layer is formed from in situ-generated aryl diazonium cations. To the distal end of the MW, a redox probe 1,1'-di(aminomethyl)ferrocene (FDMA) was attached followed by the covalent attachment of an epitope N-glycosylated pentapeptide (GPP), an analogon to HbA1c, to which an anti-HbA1c monocolonal antibody IgG can selectively bind. HbA1c was detected by a competitive inhibition assay based on the competition for binding to anti-HbA1c IgG antibodies between the analyte in solution, HbA1c, and the surface bound epitope GPP. Exposure of the GPP modified sensing interface to the mixture of anti-HbA1c IgG antibody and HbA1c results in the attenuation of ferrocene electrochemistry due to free antibody binding to the interface. Higher concentrations of analyte led to higher Faradaic currents as less anti-HbA1c IgG is available to bind to the electrode surface. It was observed that there is a good linear relationship between the relative Faradaic current of FDMA and the concentration of HbA1c from 4.5% to 15.1% of total haemoglobin in serum without the need for washing or rinsing steps.

  13. Shifting from glucose diagnosis to the new HbA1c diagnosis reduces the capability of the Finnish Diabetes Risk Score (FINDRISC) to screen for glucose abnormalities within a real-life primary healthcare preventive strategy

    PubMed Central

    2013-01-01

    Background To investigate differences in the performance of the Finnish Diabetes Risk Score (FINDRISC) as a screening tool for glucose abnormalities after shifting from glucose-based diagnostic criteria to the proposed new hemoglobin (Hb)A1c-based criteria. Methods A cross-sectional primary-care study was conducted as the first part of an active real-life lifestyle intervention to prevent type 2 diabetes within a high-risk Spanish Mediterranean population. Individuals without diabetes aged 45-75 years (n = 3,120) were screened using the FINDRISC. Where feasible, a subsequent 2-hour oral glucose tolerance test and HbA1c test were also carried out (n = 1,712). The performance of the risk score was calculated by applying the area under the curve (AUC) for the receiver operating characteristic, using three sets of criteria (2-hour glucose, fasting glucose, HbA1c) and three diagnostic categories (normal, pre-diabetes, diabetes). Results Defining diabetes by a single HbA1c measurement resulted in a significantly lower diabetes prevalence (3.6%) compared with diabetes defined by 2-hour plasma glucose (9.2%), but was not significantly lower than that obtained using fasting plasma glucose (3.1%). The FINDRISC at a cut-off of 14 had a reasonably high ability to predict diabetes using the diagnostic criteria of 2-hour or fasting glucose (AUC = 0.71) or all glucose abnormalities (AUC = 0.67 and 0.69, respectively). When HbA1c was used as the primary diagnostic criterion, the AUC for diabetes detection dropped to 0.67 (5.6% reduction in comparison with either 2-hour or fasting glucose) and fell to 0.55 for detection of all glucose abnormalities (17.9% and 20.3% reduction, respectively), with a relevant decrease in sensitivity of the risk score. Conclusions A shift from glucose-based diagnosis to HbA1c-based diagnosis substantially reduces the ability of the FINDRISC to screen for glucose abnormalities when applied in this real-life primary-care preventive strategy. PMID

  14. Hemoglobin

    MedlinePlus

    ... Failure of the right side of the heart ( cor pulmonale ) Severe chronic obstructive pulmonary disease (COPD) Scarring or ... chronic disease Aplastic anemia Bleeding CBC blood test Cor pulmonale Diabetes Drug-induced immune hemolytic anemia Erythropoietin test ...

  15. HbA1c as a Diagnostic Test for Diabetes Mellitus – Reviewing the Evidence

    PubMed Central

    Florkowski, Chris

    2013-01-01

    The evidence base in support of HbA1c as a diagnostic test for diabetes mellitus is focused on predicting a clinical outcome, considered to be the pinnacle of the Stockholm Hierarchy applied to reference intervals and clinical decision limits. In the case of diabetes, the major outcome of interest is the long term microvascular complications for which a large body of data has been accumulated, leading to the endorsement of HbA1c for diagnosis in many countries worldwide, with some variations in cut-offs and testing strategies. PMID:24151343

  16. Determination Of Ph Including Hemoglobin Correction

    DOEpatents

    Maynard, John D.; Hendee, Shonn P.; Rohrscheib, Mark R.; Nunez, David; Alam, M. Kathleen; Franke, James E.; Kemeny, Gabor J.

    2005-09-13

    Methods and apparatuses of determining the pH of a sample. A method can comprise determining an infrared spectrum of the sample, and determining the hemoglobin concentration of the sample. The hemoglobin concentration and the infrared spectrum can then be used to determine the pH of the sample. In some embodiments, the hemoglobin concentration can be used to select an model relating infrared spectra to pH that is applicable at the determined hemoglobin concentration. In other embodiments, a model relating hemoglobin concentration and infrared spectra to pH can be used. An apparatus according to the present invention can comprise an illumination system, adapted to supply radiation to a sample; a collection system, adapted to collect radiation expressed from the sample responsive to the incident radiation; and an analysis system, adapted to relate information about the incident radiation, the expressed radiation, and the hemoglobin concentration of the sample to pH.

  17. Hemoglobin Labeled by Radioactive Lysine

    DOE R&D Accomplishments Database

    Bale, W. F.; Yuile, C. L.; DeLaVergne, L.; Miller, L. L.; Whipple, G. H.

    1949-12-08

    This paper reports on the utilization of tagged epsilon carbon of DL-lysine by a dog both anemic and hypoproteinemic due to repeated bleeding plus a diet low in protein. The experiment extended over period of 234 days, a time sufficient to indicate an erythrocyte life span of at least 115 days based upon the rate of replacement of labeled red cell proteins. The proteins of broken down red cells seem not to be used with any great preference for the synthesis of new hemoglobin.

  18. Hydroxy methoxy benzaldehyde from Sesbania grandilfora inhibits the advanced glycation end products (AGEs)-mediated fibrillation in hemoglobin.

    PubMed

    Prasanna, G; Hari, N; Saraswathi, N T

    2017-03-20

    The present study was aimed to identify the active anti-glycation constituent from the leaves of Sesbania grandiflora. Characterization of the active constituent resulted in the identification of hydroxy methoxy benzaldehyde (HMB). The potential of HMB as anti-glycation lead was analyzed by fluorescence spectroscopy, fluorescence microscopy, scanning electron microscopy (SEM) and molecular interaction studies. Our results suggested that HMB inhibited formation of early (HbA1c) and advanced glycation end products (AGEs). The amyloid-like fibrillation in hemoglobin was also inhibited by HMB. SEM images indicated the protective effect against the formation of acanthocytes. Molecular docking studies showed that HMB was interacting with hemoglobin through hydrogen bonds with Arg141, Tyr140, and Thr137. Our findings suggest that HMB could be a better anti-glycation lead molecule towards novel AGEs inhibitors.

  19. Serum Uric Acid Levels were Dynamically Coupled with Hemoglobin A1c in the Development of Type 2 Diabetes

    NASA Astrophysics Data System (ADS)

    Wei, Fengjiang; Chang, Baocheng; Yang, Xilin; Wang, Yaogang; Chen, Liming; Li, Wei-Dong

    2016-06-01

    The aim of the study was to decipher the relationship between serum uric acid (SUA) and glycated hemoglobin A1c (HbA1c) or fasting plasma glucose (FPG) in both type 2 diabetes mellitus (T2DM) patients and normal subjects. A total of 2,250 unrelated T2DM patients and 4,420 Han Chinese subjects from a physical examination population were recruited for this study. In T2DM patients SUA levels were negatively correlated with HbA1c (rs = ‑0.109, P = 0.000) and 2 h plasma glucose levels (rs = ‑0.178, P = 0.000). In the physical examination population, SUA levels were inversely correlated with HbA1c (rs = ‑0.175, P = 0.000) and FPG (rs = ‑0.131, P = 0.009) in T2DM patients but positively correlated with HbA1c (rs = 0.040, P = 0.012) and FPG (rs = 0.084, P = 0.000) in normal-glucose subjects. Multivariate analyses showed that HbA1c was significantly negatively associated with HUA both in T2DM patients (OR = 0.872, 95% CI: 0.790~0.963) and in the physical examination T2DM patients (OR = 0.722, 95% CI: 0.539~0.968). Genetic association studies in T2DM patients showed that alleles of two glucose-uric acid transporter genes, ABCG2 and SLC2A9 were significantly associated with SUA levels (P < 0.05). SUA level is inversely correlated with HbA1c in T2DM patients but positively correlated with HbA1c in normal-glucose subjects. The reverse transporting of uric acid and glucose in renal tubules might be accounted for these associations.

  20. Hemoglobin Brigham (α2Aβ2100 Pro→Leu). HEMOGLOBIN VARIANT ASSOCIATED WITH FAMILIAL ERYTHROCYTOSIS

    PubMed Central

    Lokich, Jacob J.; Moloney, William C.; Bunn, H. Franklin; Bruckheimer, Sally M.; Ranney, Helen M.

    1973-01-01

    Erythrocytosis associated with the presence of a hemoglobin with increased oxygen affinity has been reported for 10 hemoglobin variants, most of which demonstrate altered electrophoretic mobility. Several members of a family were found to have erythrocytosis, and both the whole blood and the hemoglobin exhibited increased oxygen affinity. Phosphate-free hemoglobin solutions had a normal Bohr effect and reactivity to 2,3-diphosphoglycerate. The electrophoretic properties of the hemoglobin were normal, but on peptide mapping of a tryptic digest of the isolated β-chains, a normal βT11 peptide and an abnormal βT11 with greater Rf were seen. Analysis of the abnormal peptide showed the substitution of leucine for the normal proline at β100 (helical residue G2). The hemoglobin variant, designated Hb Brigham, serves to emphasize the necessity for detailed evaluation of the structure and function of hemoglobin in familial erythrocytosis even with electrophoretically “normal” hemoglobin. PMID:4719677

  1. Elevated glycated hemoglobin levels may increase the risk of atrial fibrillation in patients with diabetes mellitus

    PubMed Central

    Yang, Yu-Fan; Zhu, Wen-Qing; Cheng, Kuan; Chen, Qing-Xing; Xu, Ye; Pang, Yang; Liu, Gui-Jian; Ge, Jun-Bo

    2015-01-01

    Background: As the most common cardiac arrhythmia, atrial fibrillation (AF) is always accompanied with various complications if without detection and treatment timely. Blood-based pleiotropic molecule biomarkers have now been popularly applied in clinical detection. We hence performed this meta-analysis to evaluate the correlation of serum glycated hemoglobin (HbA1c) levels with the risk of AF in patients with diabetes mellitus (DM). Methods: Covering myriads of computerized databases, we identified potential relevant studies for statistical analysis. We used a standard reporting form to extract data from each included study. Newcastle-Ottawa Scale (NOS) criteria was used for methodological quality assessment. Statistical analyses were conducted with the STATA statistical software. Results: Six cohort studies in full text fulfilled our inclusion criteria, and following overestimation indicated that serum levels of HbA1c in DM patients with AF was higher than that in DM patients without AF (SMD = 0.67, 95% CI: 0.39-0.94, P < 0.001). Subgroup analyses by sample size and detection method implicated that elevated serum HbA1c levels exhibited significant correlations with an increased risk of AF in DM patients in the large-size subgroup (n ≥ 200), the small-size subgroup (n < 200), the high performance liquid chromatography (HPLC) subgroup and the non-HPLC subgroup (Large-size: SMD = 0.70, 95% CI: 0.38-1.03, P < 0.001; Small-size: SMD = 0.64, 95% CI: 0.09-1.19, P = 0.023; HPLC: SMD = 0.81, 95% CI: 0.49-1.12, P < 0.001; Non-HPLC: SMD = 0.36, 95% CI: 0.04-0.68, P = 0.029; respectively). Conclusion: Elevated serum HbA1c levels may be associated with an increased risk of AF in DM patients, possibly reflecting that serum HbA1c level might be a potential biomarker in the prediction of AF in DM patients. PMID:26064216

  2. Local Population Characteristics and Hemoglobin A1c Testing Rates among Diabetic Medicare Beneficiaries

    PubMed Central

    Yasaitis, Laura C.; Bubolz, Thomas; Skinner, Jonathan S.; Chandra, Amitabh

    2014-01-01

    Background Proposed payment reforms in the US healthcare system would hold providers accountable for the care delivered to an assigned patient population. Annual hemoglobin A1c (HbA1c) tests are recommended for all diabetics, but some patient populations may face barriers to high quality healthcare that are beyond providers' control. The magnitude of fine-grained variations in care for diabetic Medicare beneficiaries, and their associations with local population characteristics, are unknown. Methods HbA1c tests were recorded for 480,745 diabetic Medicare beneficiaries. Spatial analysis was used to create ZIP code-level estimated testing rates. Associations of testing rates with local population characteristics that are outside the control of providers – population density, the percent African American, with less than a high school education, or living in poverty – were assessed. Results In 2009, 83.3% of diabetic Medicare beneficiaries received HbA1c tests. Estimated ZIP code-level rates ranged from 71.0% in the lowest decile to 93.1% in the highest. With each 10% increase in the percent of the population that was African American, associated HbA1c testing rates were 0.24% lower (95% CI −0.32–−0.17); for identical increases in the percent with less than a high school education or the percent living in poverty, testing rates were 0.70% lower (−0.95–−0.46) and 1.6% lower (−1.8–−1.4), respectively. Testing rates were lowest in the least and most densely populated ZIP codes. Population characteristics explained 5% of testing rate variations. Conclusions HbA1c testing rates are associated with population characteristics, but these characteristics fail to explain the vast majority of variations. Consequently, even complete risk-adjustment may have little impact on some process of care quality measures; much of the ZIP code-related variations in testing rates likely result from provider-based differences and idiosyncratic local factors not related to

  3. Relation between glycosylated hemoglobin and lipid and thyroid hormone among patients with type 2 diabetes mellitus at King Abdulaziz Medical City, Riyadh

    PubMed Central

    Karar, Tarig; Alhammad, Rayan Ibrahim S.; Fattah, Mohamed Abdel; Alanazi, Abdullah; Qureshi, Shoeb

    2015-01-01

    Background: The main objectives of this study were to: (1) Evaluate the levels of thyroid hormones and glycosylated hemoglobin (HbA1c) among patients, (2) correlate between thyroid hormones and HbA1c and different types of lipids and HbA1c among diabetic patients. Materials and Methods: A retrospective chart review study was conducted at Department of Clinical Chemistry, King Abdulaziz Medical City (KAMC) in Riyadh, Saudi Arabia, during the period from August 2014 to December 2014, including 100 male and female patients diagnosed with diabetes mellitus (DM) type 2 and excluding patients with DM type 1. These patients were admitted to the hospital in 2013. Biochemical laboratory results were retrieved from biochemistry laboratory database while age and sex of patients were retrieved from patient files. Statistical analysis was performed using SPSS software conducting frequency analysis and correlation test. Results: The result showed increased mean levels of HbA1c (8.4%) and normal level of thyroid stimulating hormone (TSH) (4.5 mlU/L) and T4 (14.1 pmol/L). The results also showed a weak positive correlation between HbA1c and TSH (r = 0.212, P = 0.034) and insignificant correlation with thyroxin T4 (r = −0.018, P = 0.855). There was a weak positive correlation between HbA1c and total cholesterol and low density lipoprotein (r = 0.258, P = 0.001), (r = 0.297, P = 0.003), respectively. Conclusion: It is concluded that increased blood glucose could trigger anterior pituitary gland to increase secretion of TSH, whereas there was no direct correlation between increased glycemic index and the rate of thyroxine secretion. Furthermore, it is concluded that there is an association between blood glucose and some lipid markers. PMID:26604625

  4. [Evaluation of HbA1c using different methods in haemoglobin variant, Hb J-Bangkok].

    PubMed

    Sawaragi, Wakana; Shibuya, Hitoshi; Yasuda, Keiko; Suzuki, Haruki; Shimizu, Chikara; Matsuno, Kazuhiko

    2009-05-01

    A 31-year-old Japanese man with haemoglobin variant, Hb J-Bangkok [beta56 (D7) Gly-->Asp], was found by discrepant values between HbA1c and glycated-albumin. We measured HbA1c using three different methods, HPLC, enzyme assay and turbidimetric immunoassay. HbA1c value measured by HPLC was much lower than those by others. Furthermore, we estimated calculated glyco-haemoglobin value measured by high-resolution HPLC, revealing that HbA1c values measured by enzyme assay and turbidimetric immunoassay were comparable with calculated value. When measuring HbA1c value in haemoglobin variant, Hb J Bangkok, enzyme assay and turbidimetric immunoassay are useful methods.

  5. Nanoscale spectroscopy and imaging of hemoglobin.

    PubMed

    Kennedy, Eamonn; Yarrow, Fiona; Rice, James H

    2011-09-01

    Sub diffraction limited infrared absorption imaging of hemoglobin was performed by coupling IR optics with an atomic force microscope. Comparisons between the AFM topography and IR absorption images of micron sized hemoglobin features are presented, along with nanoscale IR spectroscopic analysis of the metalloprotein.

  6. Spectrophotometric Properties of Hemoglobin: Classroom Applications.

    ERIC Educational Resources Information Center

    Frary, Roger

    1997-01-01

    Discusses simple and safe techniques that can be used in the educational laboratory to study hemoglobin. Discusses the spectral properties of hemoglobin, spectral-absorbence curves of oxyhemoglobin and carboxyhemoglobin, tracking the conversion of oxyhemoglobin to methemoglobin, and changing from the oxyhemoglobin to deoxyhemoglobin conformation.…

  7. Optical detection of glucose and glycated hemoglobin using etched fiber Bragg gratings coated with functionalized reduced graphene oxide.

    PubMed

    Sridevi, S; Vasu, K S; Sampath, S; Asokan, S; Sood, A K

    2016-07-01

    An enhanced optical detection of D-glucose and glycated hemoglobin (HbA1c ) has been established in this study using etched fiber Bragg gratings (eFBG) coated with aminophenylboronic acid (APBA)-functionalized reduced graphene oxide (RGO). The read out, namely the shift in Bragg wavelength (ΔλB ) is highly sensitive to changes that occur due to the adsorption of glucose (or HbA1c ) molecules on the eFBG sensor coated with APBA-RGO complex through a five-membered cyclic ester bond formation between glucose and APBA molecules. A limit of detection of 1 nM is achieved with a linear range of detection from 1 nM to 10 mM in the case of D-glucose detection experiments. For HbA1c , a linear range of detection varying from 86 nM to 0.23 mM is achieved. The observation of only 4 pm (picometer) change in ΔλB even for the 10 mM lactose solution confirms the specificity of the APBA-RGO complex coated eFBG sensors to glucose molecules.

  8. Evaluation of hemoglobin A1c measurement from filter paper using high-performance liquid chromatography and immunoturbidimetric assay.

    PubMed

    Wu, Yonghua; Yang, Xu; Wang, Haining; Li, Zhenrong; Wang, Tiancheng

    2017-04-01

    Glycated hemoglobin (HbA1c) measurement from whole blood (WB) samples is inconvenient for epidemic surveillance and self-monitoring of glycemic level. We evaluated HbA1c measurement from WB blotted on filter paper (FP), which can be easily transported to central laboratories, with high-performance liquid chromatography (HPLC) and immunoturbidimetric assay (ITA). WB was applied to Whatman filter paper. By using HPLC and WB samples as reference methods, these FP samples were evaluated on HPLC and ITA. Inter- and intra-assay variation, WB vs. FP agreement and sample stability at 20-25 °C and -70 °C were assessed by statistical analysis. Results showed that the coefficient of variation (CV, %) of FP samples for HPLC and ITA were 0.44-1.02% and 1.47-2.72%, respectively (intra-assay); 2.13-3.56% and 3.21-4.82%, respectively (inter-assay). The correlation of WB HPLC with FP analyzed using HPLC and ITA are both significant (p < 0.001). Sample stability showed that FP method up to 5 days at 20-25 °C and 5 weeks at -70 °C is accurate and reproducible. In conclusion, FP samples analyzed by HPLC and ITA can both provide an alternative to WB for HbA1c measurement, supporting the use of FP method in epidemic surveillance and healthcare units.

  9. Determination of Human Hemoglobin Derivatives.

    PubMed

    Attia, Atef M M; Ibrahim, Fatma A A; Abd El-Latif, Noha A; Aziz, Samir W; Abdelmottaleb Moussa, Sherif A; Elalfy, Mohsen S

    2015-01-01

    The levels of the inactive hemoglobin (Hb) pigments [such as methemoglobin (metHb), carboxyhemoglobin (HbCO) and sulfohemoglobin (SHb)] and the active Hb [in the oxyhemoglobin (oxyHb) form] as well as the blood Hb concentration in healthy non pregnant female volunteers were determined using a newly developed multi-component spectrophotometric method. The results of this method revealed values of SHb% in the range (0.0727-0.370%), metHb% (0.43-1.0%), HbCO% (0.4-1.52%) and oxyHb% (97.06-98.62%). Furthermore, the results of this method revealed values of blood Hb concentration in the range (12.608-15.777 g/dL). The method is highly sensitive, accurate and reproducible.

  10. Monoclonal antibodies specific for sickle cell hemoglobin

    SciTech Connect

    Jensen, R.H.; Vanderlaan, M.; Grabske, R.J.; Branscomb, E.W.; Bigbee, W.L.; Stanker, L.H.

    1985-01-01

    Two mouse hybridoma cell lines were isolated which produce monoclonal antibodies that bind hemoglobin S. The mice were immunized with peptide-protein conjugates to stimulate a response to the amino terminal peptide of the beta chain of hemoglobin S, where the single amino acid difference between A and S occurs. Immunocharacterization of the antibodies shows that they bind specifically to the immunogen peptide and to hemoglobin S. The specificity for S is high enough that one AS cell in a mixture with a million AA cells is labeled by antibody, and such cells can be analyzed by flow cytometry. Immunoblotting of electrophoretic gels allows definitive identification of hemoglobin S as compared with other hemoglobins with similar electrophoretic mobility. 12 references, 4 figures.

  11. Degradation of human hemoglobin by Prevotella intermedia.

    PubMed

    Guan, Su-Min; Nagata, Hideki; Shizukuishi, Satoshi; Wu, Jun-Zheng

    2006-01-01

    In this study, the ability of Prevotella intermedia, an obligate anaerobic rod, to degrade human hemoglobin was determined by SDS-PAGE and the degradation was quantified by scanning densitometry. Both bacterial cells and culture supernatants degraded hemoglobin. The hemoglobin degradation by P. intermedia was time-dependent, heat sensitive, pH related and was not influenced by iron restriction. Inhibition studies demonstrated that a cysteine protease might be involved in hemoglobin degradation and this protease might require metal ions for its activity and it might be thiol-requiring and trypsin-inducible. The results indicate that P. intermedia is capable to release heme from hemoglobin, hence provide a source of iron for its proliferation.

  12. Structure and reactivity of hexacoordinate hemoglobins

    PubMed Central

    Kakar, Smita; Hoffman, Federico G.; Storz, Jay F.; Fabian, Marian; Hargrove, Mark S.

    2015-01-01

    The heme prosthetic group in hemoglobins is most often attached to the globin through coordination of either one or two histidine side chains. Those proteins with one histidine coordinating the heme iron are called “pentacoordinate” hemoglobins, a group represented by red blood cell hemoglobin and most other oxygen transporters. Those with two histidines are called “hexacoordinate hemoglobins”, which have broad representation among eukaryotes. Coordination of the second histidine in hexacoordinate Hbs is reversible, allowing for binding of exogenous ligands like oxygen, carbon monoxide, and nitric oxide. Research over the past several years has produced a fairly detailed picture of the structure and biochemistry of hexacoordinate hemoglobins from several species including neuroglobin and cytoglobin in animals, and the nonsymbiotic hemoglobins in plants. However, a clear understanding of the physiological functions of these proteins remains an elusive goal. PMID:20933319

  13. Analysis of Hemoglobin Glycation Using Microfluidic CE-MS: A Rapid, Mass Spectrometry Compatible Method for Assessing Diabetes Management.

    PubMed

    Redman, Erin A; Ramos-Payan, Maria; Mellors, J Scott; Ramsey, J Michael

    2016-05-17

    Diabetes has become a significant health problem worldwide with the rate of diagnosis increasing rapidly in recent years. Measurement of glycated blood proteins, particularly glycated hemoglobin (HbA1c), is an important diagnostic tool used to detect and manage the condition in patients. Described here is a method using microfluidic capillary electrophoresis with mass spectrometry detection (CE-MS) to assess hemoglobin glycation in whole blood lysate. Using denaturing conditions, the hemoglobin (Hb) tetramer dissociates into the alpha and beta subunits (α- and β-Hb), which are then separated via CE directly coupled to MS detection. Nearly baseline resolution is achieved between α-Hb, β-Hb, and glycated β-Hb. A second glycated β-Hb isomer that is partially resolved from β-Hb is detected in extracted ion electropherograms for glycated β-Hb. Glycation on α-Hb is also detected in the α-Hb mass spectrum. Additional modifications to the β-Hb are detected, including acetylation and a +57 Da species that could be the addition of a glyoxal moiety. Patient blood samples were analyzed using the microfluidic CE-MS method and a clinically used immunoassay to measure HbA1c. The percentage of glycated α-Hb and β-Hb was calculated from the microfluidic CE-MS data using peak areas generated from extracted ion electropherograms. The values for glycated β-Hb were found to correlate well with the HbA1c levels derived in the clinic, giving a slope of 1.20 and an R(2) value of 0.99 on a correlation plot. Glycation of human serum albumin (HSA) can also be measured using this technique. It was observed that patients with elevated glycated Hb levels also had higher levels of HSA glycation. Interestingly, the sample with the highest HbA1c levels did not have the highest levels of glycated HSA. Because the lifetime of HSA is shorter than Hb, this could indicate a recent lapse in glycemic control for that patient. The ability to assess both Hb and HSA glycation has the potential

  14. Evaluation of serum zinc status and glycated hemoglobin of type 2 diabetes mellitus patients in a tertiary care hospital of assam.

    PubMed

    Saharia, Gautom Kumar; Goswami, Rohini Kanta

    2013-01-01

    The present study was undertaken to find out any correlation between serum zinc concentration and HbA1C% in patients with type 2 diabetes mellitus (DM). The study was carried out on 50 newly diagnosed patients of type 2 diabetes and controls in the Department of Biochemistry, Assam Medical College and Hospital, Dibrugarh. Analyses of blood glucose (fasting and postprandial), glycated hemoglobin (HbA1c), serum zinc, urea, and creatinine concentrations were performed by standard methods. Concentrations of fasting and postprandial blood glucose were significantly higher in the diabetic group than controls (P < 0.001) and the mean HbA1c% was also higher in cases (8.32% ±1.58%). The mean serum zinc concentration in cases was found to be significantly lower than controls (79.85 ± 13.4 vs. 109.74 ± 9.72 μg/dL) and P < 0.001 with correlation coefficient r = -0.804. Present study revealed an inverse relationship between HbA1C% and serum zinc concentration in patients with type 2 DM, substantiated by regression analysis.

  15. Raman spectroscopy and PCA-SVM as a non-invasive diagnostic tool to identify and classify qualitatively glycated hemoglobin levels in vivo.

    PubMed

    Villa-Manríquez, J F; Castro-Ramos, J; Gutiérrez-Delgado, F; Lopéz-Pacheco, M A; Villanueva-Luna, A E

    2016-12-23

    In this study we identify and classify high and low levels of glycated hemoglobin (HbA1c) in healthy volunteers (HV) and diabetic patients (DP). Overall, 86 subjects were evaluated. The Raman spectrum was measured in three anatomical regions of the body: index fingertip, right ear lobe, and forehead. The measurements were performed to compare the difference between the HV and DP (22 well controlled diabetic patients (WCDP) (HbA1c <6.5%), and 49 not controlled diabetic patients (NCDP) (HbA1c ≥6.5%)). Multivariable methods such as principal components analysis (PCA) combined with support vector machine (SVM) were used to develop effective diagnostic algorithms for classification among these groups. The forehead of HV versus WCDP showed the highest sensitivity (100%) and specificity (100%). Sensitivity (100%) and specificity (60%), were highest in the forehead of WCDP, versus NCDP. In HV versus NCDP, the fingertip had the highest sensitivity (100%) and specificity (80%). The efficacy of the diagnostic algorithm by receiver operating characteristic (ROC) curve was confirmed. Overall, our study demonstrated that the combination of Raman spectroscopy and PCA-SVM are feasible non-invasive diagnostic tool in diabetes to classify qualitatively high and low levels of HbA1c in vivo.

  16. Assessing endothelial dysfunction in adolescents and young adults with type 1 diabetes mellitus using a non-invasive heat stimulus

    PubMed Central

    Shah, Amy S.; Gao, Zhiqian; Dolan, Lawrence M.; Dabelea, Dana; D'Agostino, Ralph B.; Urbina, Elaine M.

    2015-01-01

    Background Microvascular dysfunction is a key event in the development of atherosclerosis, which predates the clinical manifestations of vascular disease including stroke and myocardial infarction. Dysfunction of the microvasculature can be measured as a decreased microperfusion in response to heat. Objective We sought to evaluate the microvasculature using heat among adolescents and young adults with type 1 diabetes (T1D) compared to healthy non-diabetic controls. We hypothesized that youth with T1D would have impaired microvascular function measured as decreased perfusion. Methods We studied 181 adolescents and young adults with T1D and 96 age-, race-, and sex-matched healthy controls (mean age 19 yr). Patients were seen at an in-person study visit where demographics, anthropometrics, and laboratory data was obtained. Skin microvascular perfusion was measured on the volvar surface of the right forearm using a standard laser flow Doppler. Measurements were taken at baseline and after heating to 44° C. Results Youth with T1D had decreased microvascular perfusion as measured by lower percent change of perfusion units (1870 ± 945 vs. 2539 ± 1255, p < 0.01) and percent change in area under the curve (1870 ± 945 vs. 2539 ± 1255, p < 0.01) compared to controls. Glycosylated hemoglobin A1c (HbA1c) was found to be an independent determinant of microvascular function (p < 0.05). Conclusions Adolescents and young adults with T1D have evidence of microvascular dysfunction that can be detected using heat, a non-invasive physiologic stimulus. HbA1c appears to play an independent role in determining microvascular perfusion suggesting tight glycemic control is probably important for the development of vascular disease. PMID:25082568

  17. Mössbauer studies of hemoglobin in high altitude polycythemia

    NASA Astrophysics Data System (ADS)

    Xiufang, Zhang; Linming, Shen; Songsen, Chen; Yuanyuan, Liu; Naifei, Gao; Yuanming, Zheng; Zhaohui, Ao; Liangquan, Shong

    1990-07-01

    The Mössbauer spectra have been measured in erythrocytes from normal adults and the patients with high altitude polycythemia (HAPC). The results indicated that two subspectra “a” and “b”, corresponding to oxy- and deoxyhemoglobin respectively, were present in all blood samples, and a third subspectrum “c” was found to exist in almost all samples from the patients. The parameters of the third subspectra “cl” in most samples from the patients were similar to those of carbon monoxyhemoglobin. The components were considered to be the denatured hemoglobin in RBCs (red blood cells). Together with clinical analysis, a possible mechanism of HAPC has been discussed.

  18. Association of diabetes with tooth loss in Hispanic/Latino adults: findings from the Hispanic Community Health Study/Study of Latinos

    PubMed Central

    Greenblatt, Ariel P; Salazar, Christian R; Northridge, Mary E; Kaplan, Robert C; Taylor, George W; Finlayson, Tracy L; Qi, Qibin; Badner, Victor

    2016-01-01

    Objectives To investigate the association between diabetes mellitus and missing teeth in Hispanic/Latino adults from diverse heritage groups who reside in the USA. Research design and methods The Hispanic Community Health Study/Study of Latinos (HCHS/SOL) is a multicenter, population-based study of 18–74 years old who underwent a physical and oral examination (n=15 945). Glycemic status was categorized as diabetes, impaired, or normal, based on medication use, and American Diabetes Association criteria for fasting glucose and glycosylated hemoglobin (HbA1c). HbA1c<7% indicated good glycemic control, and HbA1c>7% indicated uncontrolled diabetes. We estimated ORs and 95% CIs for missing >9 teeth and being edentulous (missing all natural teeth), after adjustment for age, income, education, Hispanic background, study site/center, nativity, last dental visit, health insurance, diet quality, cigarette smoking, obesity, periodontitis, and C reactive protein. Results Persons with uncontrolled diabetes had a significant increased likelihood of missing >9 teeth and being edentulous as compared with persons with normal glycemic status (adjusted OR=1.92, 95% CI 1.44 to 2.55 and adjusted OR=1.73, 95% CI 1.22 to 2.46, respectively). The association appeared to be stronger at younger ages (18–44 years old; p for interaction <0.0001). However, we found no associations of either impaired glycemia or controlled diabetes with tooth loss in adjusted models. Conclusions Dentists should be aware of their Hispanic patients' diabetes status and whether or not they are well controlled, because these may affect tooth loss and impair oral function, which can lead to poor nutrition and complications of diabetes. PMID:27239319

  19. Properties of a recombinant human hemoglobin with aspartic acid 99(beta), an important intersubunit contact site, substituted by lysine.

    PubMed Central

    Yanase, H.; Cahill, S.; Martin de Llano, J. J.; Manning, L. R.; Schneider, K.; Chait, B. T.; Vandegriff, K. D.; Winslow, R. M.; Manning, J. M.

    1994-01-01

    Site-directed mutagenesis of an important subunit contact site, Asp-99(beta), by a Lys residue (D99K(beta)) was proven by sequencing the entire beta-globin gene and the mutant tryptic peptide. Oxygen equilibrium curves of the mutant hemoglobin (Hb) (2-15 mM in heme) indicated that it had an increased oxygen affinity and a lowered but significant amount of cooperativity compared to native HbA. However, in contrast to normal HbA, oxygen binding of the recombinant mutant Hb was only marginally affected by the allosteric regulators 2,3-diphosphoglycerate or inositol hexaphosphate and was not at all responsive to chloride. The efficiency of oxygen binding by HbA in the presence of allosteric regulators was limited by the mutant Hb. At concentrations of 0.2 mM or lower in heme, the mutant D99K(beta) Hb was predominantly a dimer as demonstrated by gel filtration, haptoglobin binding, fluorescence quenching, and light scattering. The purified dimeric recombinant Hb mutant exists in 2 forms that are separable on isoelectric focusing by about 0.1 pH unit, in contrast to tetrameric hemoglobin, which shows 1 band. These mutant forms, which were present in a ratio of 60:40, had the same masses for their heme and globin moieties as determined by mass spectrometry. The elution positions of the alpha- and beta-globin subunits on HPLC were identical. Circular dichroism studies showed that one form of the mutant Hb had a negative ellipticity at 410 nm and the other had positive ellipticity at this wavelength. The findings suggest that the 2 D99K(beta) recombinant mutant forms have differences in their heme-protein environments. PMID:7987216

  20. Hemoglobin Concentration and Cognitive Impairment in the Renal REasons for Geographic And Racial Differences in Stroke (REGARDS) Study

    PubMed Central

    Wadley, Virginia G.; Newsome, Britt B.; Zakai, Neil A.; McClure, Leslie A.; Howard, George; Warnock, David G.; McClellan, William

    2010-01-01

    Background. There is growing interest in determining the degree of anemia, which is clinically significant. The goal of this study was to determine the association between hemoglobin concentration and cognitive impairment in a large sample of U.S. adults. Methods. We used cross-sectional data from 19,701 adults participating in the REasons for Geographic And Racial Differences in Stroke study. Cognitive impairment was defined as a score of 4 or less on the six-item screener. Hemoglobin was analyzed in 1 g/dL increments relative to the World Health Organization (WHO) threshold (<13 g/dL for men and <12 g/dL for women). Results. The mean hemoglobin concentration was 13.7 ± 1.5 g/dL. The prevalence of cognitive impairment increased from 4.3% among individuals with a hemoglobin >3 g/dL above the WHO threshold to 16.8% for those with a hemoglobin ≥2 g/dL below the WHO threshold. After adjustment for demographics, chronic health conditions, health status, and inflammation, the association between reduced hemoglobin and cognitive impairment was attenuated and no longer significant, including among those with hemoglobin ≥2 g/dL below the WHO threshold (odds ratio 1.39, 95% confidence interval = 0.94–2.04). A test for linear trend was of borderline significance (p value = .06). For 94% of the sample within 2 g/dL of the WHO threshold, there was no relationship between hemoglobin concentration and the odds of cognitive impairment. The associations did not differ by sex and race. Conclusions. Within a large sample of community-dwelling adults, there was no significant association between hemoglobin concentration and cognitive impairment after multivariable adjustment. PMID:20634281

  1. UV-B protective effect of a polyacylated anthocyanin, HBA, in flower petals of the blue morning glory, Ipomoea tricolor cv. Heavenly Blue.

    PubMed

    Mori, Mihoko; Yoshida, Kumi; Ishigaki, Yasuhito; Matsunaga, Tsukasa; Nikaido, Osamu; Kameda, Kiyoshi; Kondo, Tadao

    2005-03-15

    The protective effects of polyacylated anthocyanin, heavenly blue anthocyanin (HBA), in blue flower petals of morning glory (Ipomoea tricolor cv. Heavenly Blue) against UV-B induced DNA damage were examined. We first clarified the concentration of HBA in epidermal vacuoles to be 12mM, and then constructed a UV-B irradiating apparatus resembling flower petal tissue to assess the screening effect of HBA. Monochromatic (280 and 310nm) or broad UV-B induced DNA lesions were reduced completely by the HBA filter to the same molecular numbers as those in living petal epidermis. However, diluted HBA solution and trisdeacyl HBA did not have the same reduction effect. HBA was more tolerant to solar radiation than trisdeacyl HBA. These data strongly suggest that polyacylated anthocyanins in flower petals can screen harmful UV-B efficiently. This action might be largely due to aromatic acyl residues.

  2. Mutational analysis of hemoglobin binding and heme utilization by a bacterial hemoglobin receptor.

    PubMed

    Fusco, W G; Choudhary, N R; Council, S E; Collins, E J; Leduc, I

    2013-07-01

    Iron is an essential nutrient for most living organisms. To acquire iron from their environment, Gram-negative bacteria use TonB-dependent transporters that bind host proteins at the bacterial surface and transport iron or heme to the periplasm via the Ton machinery. TonB-dependent transporters are barrel-shaped outer membrane proteins with 22 transmembrane domains, 11 surface-exposed loops, and a plug domain that occludes the pore. To identify key residues of TonB-dependent transporters involved in hemoglobin binding and heme transport and thereby locate putative protective epitopes, the hemoglobin receptor of Haemophilus ducreyi HgbA was used as a model of iron/heme acquisition from hemoglobin. Although all extracellular loops of HgbA are required by H. ducreyi to use hemoglobin as a source of iron/heme, we previously demonstrated that hemoglobin binding by HgbA only involves loops 5 and 7. Using deletion, substitution, and site-directed mutagenesis, we were able to differentiate hemoglobin binding and heme acquisition by HgbA. Deletion or substitution of the GYEAYNRQWWA region of loop 5 and alanine replacement of selected histidines affected hemoglobin binding by HgbA. Conversely, mutation of the phenylalanine in the loop 7 FRAP domain or substitution of the NRQWWA motif of loop 5 significantly abrogated utilization of heme from hemoglobin. Our findings show that hemoglobin binding and heme utilization by a bacterial hemoglobin receptor involve specific motifs of HgbA.

  3. The Importance of HbA1c Control in Patients with Subclinical Hypothyroidism

    PubMed Central

    Billic-Komarica, Edina; Beciragic, Amela; Junuzovic, Dzelaludin

    2012-01-01

    Goal: To investigate the correlation between TSH and HbA1c in the treatment of L-thyroxine in the process of glycemic control in patients with subclinical hypothyroidism. Patients and methods: The sample consisted of 100 patients, mean age 51.75±3.23 years, BMI=27.97±4.52 kg/m2, with SH (TSH>4.2 mU/L and normal serum T3 and T4). Laboratory diagnosis included the determination of free T3, free T4, thyroid antibodies, Tg, insulin, C-peptide and glucose during the OGTT, HbA1c, CRP and lipid levels. 20 patients with SH had prediabetes and 38 patients had DM. All patients were treated with low doses of L-thyroxine (25-50ug) and all were physically active. Results: After 6 months of treatment with L-thyroxine, the patients had normal or decreased TSH (5.85±0.92 vs. 3.54±0.55 mU/L), insulin levels (114.64±24.11 vs. 96.44±17.26 pmol/L) significantly reduced HbA1c (6.74±1.01 vs. 6.26±1.12) is reduced. Conclusion: The correlation between TSH and HbA1c was positive and significant (r=0.46). This indicates a significant effect of treatment with L-thyroxine on glycemic control in patients with subclinical hypothyroidism. PMID:23678326

  4. The Hemoglobin Glycation Index Identifies Subpopulations With Harms or Benefits From Intensive Treatment in the ACCORD Trial

    PubMed Central

    Liu, Shuqian; Myers, Leann; McCarter, Robert J.; Buse, John B.; Fonseca, Vivian

    2015-01-01

    OBJECTIVE This study tested the hypothesis that intensive treatment in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial disproportionately produced adverse outcomes in patients with diabetes with a high hemoglobin glycation index (HGI = observed HbA1c − predicted HbA1c). RESEARCH DESIGN AND METHODS ACCORD was a randomized controlled trial of 10,251 patients with type 2 diabetes assigned to standard or intensive treatment with HbA1c goals of 7.0% to 7.9% (53 to 63 mmol/mol) and less than 6% (42 mmol/mol), respectively. In this ancillary study, a linear regression equation (HbA1c = 0.009 × fasting plasma glucose [FPG] [mg/dL] + 6.8) was derived from 1,000 randomly extracted participants at baseline. Baseline FPG values were used to calculate predicted HbA1c and HGI for the remaining 9,125 participants. Kaplan-Meier and Cox regression were used to assess the effects of intensive treatment on outcomes in patients with a low, moderate, or high HGI. RESULTS Intensive treatment was associated with improved primary outcomes (composite of cardiovascular events) in the low (hazard ratio [HR] 0.75 [95% CI 0.59–0.95]) and moderate (HR 0.77 [95% CI 0.61–0.97]) HGI subgroups but not in the high HGI subgroup (HR 1.14 [95% CI 0.93–1.40]). Higher total mortality in intensively treated patients was confined to the high HGI subgroup (HR 1.41 [95% CI 1.10–1.80]). A high HGI was associated with a greater risk for hypoglycemia in the standard and intensive treatment groups. CONCLUSIONS HGI calculated at baseline identified subpopulations in ACCORD with harms or benefits from intensive glycemic control. HbA1c is not a one-size-fits-all indicator of blood glucose control, and taking this into account when making management decisions could improve diabetes care. PMID:25887355

  5. Glycated Hemoglobin and All-Cause and Cause-Specific Mortality in Singaporean Chinese Without Diagnosed Diabetes: The Singapore Chinese Health Study

    PubMed Central

    Bancks, Michael P.; Odegaard, Andrew O.; Pankow, James S.; Koh, Woon-Puay; Yuan, Jian-Min; Gross, Myron D.

    2014-01-01

    OBJECTIVE Glycated hemoglobin (HbA1c) is a robust biomarker of the preceding 2 to 3 months average blood glucose level. The aim of this study was to examine the association between HbA1c and mortality in a cohort of Southeast Asians. RESEARCH DESIGN AND METHODS Analysis of 7,388 men and women, mean age 62 years, from the Singapore Chinese Health Study who provided a blood sample at the follow-up I visit (1999–2004) and reported no history of diabetes, previous adverse cardiovascular events, or cancer. A total of 888 deaths were identified through 31 December 2011 via registry linkage. Participants represented a random study sample of potential control subjects for a nested case-control genome-wide association study of type 2 diabetes in the population. Hazard ratios (HRs) for all-cause and cause-specific mortality by six categories of HbA1c were estimated with Cox regression models. RESULTS Relative to participants with an HbA1c of 5.4–5.6% (36–38 mmol/mol), participants with HbA1c ≥6.5% (≥48 mmol/mol) had an increased risk of all-cause, cardiovascular, and cancer mortality during an average of 10.1 years of follow-up; HRs (95% CIs) were 1.96 (1.56–2.46), 2.63 (1.77–3.90), and 1.51 (1.04–2.18), respectively. No level of HbA1c was associated with increased risk of respiratory mortality. Levels <6.5% HbA1c were not associated with mortality during follow-up. The results did not materially change after excluding observation of first 3 years post–blood draw. CONCLUSIONS HbA1c levels consistent with undiagnosed type 2 diabetes (≥6.5%) are associated with an increased risk of all-cause and cause-specific mortality in Chinese men and women. PMID:25216509

  6. The Risk of Coronary Heart Disease Associated With Glycosylated Hemoglobin ≥ 6.5% is Pronounced in the Haptoglobin 2-2 Genotype

    PubMed Central

    Cahill, Leah E; Jensen, Majken K; Chiuve, Stephanie E; Shalom, Hadar; Pai, Jennifer K; Flint, Alan J; Mukamal, Kenneth J; Rexrode, Kathryn M; Levy, Andrew P; Rimm, Eric B

    2015-01-01

    BACKGROUND Research targeting glycosylated hemoglobin (HbA1c) to < 6.5% to prevent coronary heart disease (CHD) events has conflicting results. We previously observed the haptoglobin (Hp) Hp2-2 genotype is associated with a ~10-fold increased CHD risk among individuals with HbA1c ≥ 6.5%, and thus might be useful in identifying those at high risk of CHD who would benefit from maintaining HbA1c < 6.5%. OBJECTIVES We modeled whether HbA1c ≥ 6.5% in the Hp2-2 genotype is associated with CHD in a prospective case-control study nested within the Health Professionals Follow-Up Study (HPFS). METHODS HbA1c concentration and Hp genotype were determined for 695 incident cases of CHD from 1994–2010 and matched controls. Logistic regression models calculated relative risk (RR) and 95% confidence intervals (CI), for the first and second halves of follow-up, adjusting for confounding variables. A dataset from the Nurses’ Health Study (NHS) served as a replication cohort. RESULTS Prevalence of Hp2-2 genotype in HPFS was 39%. Compared to HbA1c < 6.5%, RR of CHD for HbA1c ≥ 6.5% for the Hp2-2 genotype over full follow-up was 3.07 (1.37–6.86)-- 3.88 (1.31–11.52) during the first half of follow-up and 2.16 (0.61–7.61) in the second half. The corresponding RRs (95% CI) for the Hp1-1 + Hp2-1 genotypes were 2.19 (1.14–4.24) (full follow-up), 1.60 (0.73–3.53) (first half), and 4.72 (1.26–17.65) (second half). CONCLUSIONS In 2 independent cohorts, risk of CHD associated with HbA1c ≥ 6.5% is pronounced in the Hp2-2 genotype, particularly in early cases. The Hp2-2 genotype may identify individuals at greatest CHD risk from hyperglycemia. PMID:26483103

  7. Preparation of Hemoglobin-Containing Microcapsules.

    DTIC Science & Technology

    1982-04-01

    L -i2 801 PREPARRTION OF HEMOGLOBIN-CONTAINING MICROCAPSULES (U) i/i I SRI INTERNATIONAL MENLO PRK CA Z REYES APR 82 UNLSSFE SRI1-2254-2 DRMDi,7-8@-C...R oI• _ AD I PREPARATION OF HEMOGLOBIN- /2 o ) CONTAINING MICROCAPSULES . 00 ANNUAL AND FINAL REPORT ZOILA REYES, Ph.D. APRIL 1982 Supported by U.S...1/31/82) PREPARATION OF HEMOGLOBIN-CONTAINING MICROCAPSULES 6. PERFORMING ORG. REPOR’ NUMBER 2254-2 7. AUTHOR(s) 8. CONTRACT OR GRANT NUMBER(s) Zoila

  8. Interaction of Human Hemoglobin with Methotrexate

    NASA Astrophysics Data System (ADS)

    Zaharia, M.; Gradinaru, R.

    2015-05-01

    This study focuses on the interaction between methotrexate and human hemoglobin using steady-state ultraviolet-visible and fluorescence quenching methods. Fluorescence quenching was found to be valuable in assessing drug binding to hemoglobin. The quenching of methotrexate is slightly smaller than the quenching observed with related analogs (dihydrofolate and tetrahydrofolate). The quenching studies were performed at four different temperatures and various pH values. The number of binding sites for tryptophan is ~1. Parameter-dependent assays revealed that electrostatic forces play an essential role in the methotrexate-hemoglobin interaction. Furthermore, the complex was easily eluted using gel filtration chromatography.

  9. Oxygenation properties and isoform diversity of snake hemoglobins

    PubMed Central

    Natarajan, Chandrasekhar; Moriyama, Hideaki; Hoffmann, Federico G.; Wang, Tobias; Fago, Angela; Malte, Hans; Overgaard, Johannes; Weber, Roy E.

    2015-01-01

    Available data suggest that snake hemoglobins (Hbs) are characterized by a combination of unusual structural and functional properties relative to the Hbs of other amniote vertebrates, including oxygenation-linked tetramer-dimer dissociation. However, standardized comparative data are lacking for snake Hbs, and the Hb isoform composition of snake red blood cells has not been systematically characterized. Here we present the results of an integrated analysis of snake Hbs and the underlying α- and β-type globin genes to characterize 1) Hb isoform composition of definitive erythrocytes, and 2) the oxygenation properties of isolated isoforms as well as composite hemolysates. We used species from three families as subjects for experimental studies of Hb function: South American rattlesnake, Crotalus durissus (Viperidae); Indian python, Python molurus (Pythonidae); and yellow-bellied sea snake, Pelamis platura (Elapidae). We analyzed allosteric properties of snake Hbs in terms of the Monod-Wyman-Changeux model and Adair four-step thermodynamic model. Hbs from each of the three species exhibited high intrinsic O2 affinities, low cooperativities, small Bohr factors in the absence of phosphates, and high sensitivities to ATP. Oxygenation properties of the snake Hbs could be explained entirely by allosteric transitions in the quaternary structure of intact tetramers, suggesting that ligation-dependent dissociation of Hb tetramers into αβ-dimers is not a universal feature of snake Hbs. Surprisingly, the major Hb isoform of the South American rattlesnake is homologous to the minor HbD of other amniotes and, contrary to the pattern of Hb isoform differentiation in birds and turtles, exhibits a lower O2 affinity than the HbA isoform. PMID:26354849

  10. Oxygenation properties and isoform diversity of snake hemoglobins.

    PubMed

    Storz, Jay F; Natarajan, Chandrasekhar; Moriyama, Hideaki; Hoffmann, Federico G; Wang, Tobias; Fago, Angela; Malte, Hans; Overgaard, Johannes; Weber, Roy E

    2015-11-01

    Available data suggest that snake hemoglobins (Hbs) are characterized by a combination of unusual structural and functional properties relative to the Hbs of other amniote vertebrates, including oxygenation-linked tetramer-dimer dissociation. However, standardized comparative data are lacking for snake Hbs, and the Hb isoform composition of snake red blood cells has not been systematically characterized. Here we present the results of an integrated analysis of snake Hbs and the underlying α- and β-type globin genes to characterize 1) Hb isoform composition of definitive erythrocytes, and 2) the oxygenation properties of isolated isoforms as well as composite hemolysates. We used species from three families as subjects for experimental studies of Hb function: South American rattlesnake, Crotalus durissus (Viperidae); Indian python, Python molurus (Pythonidae); and yellow-bellied sea snake, Pelamis platura (Elapidae). We analyzed allosteric properties of snake Hbs in terms of the Monod-Wyman-Changeux model and Adair four-step thermodynamic model. Hbs from each of the three species exhibited high intrinsic O2 affinities, low cooperativities, small Bohr factors in the absence of phosphates, and high sensitivities to ATP. Oxygenation properties of the snake Hbs could be explained entirely by allosteric transitions in the quaternary structure of intact tetramers, suggesting that ligation-dependent dissociation of Hb tetramers into αβ-dimers is not a universal feature of snake Hbs. Surprisingly, the major Hb isoform of the South American rattlesnake is homologous to the minor HbD of other amniotes and, contrary to the pattern of Hb isoform differentiation in birds and turtles, exhibits a lower O2 affinity than the HbA isoform.

  11. Diabetes mellitus: the long way of standardization of HbA(1c) to the level of highest metrological order.

    PubMed

    Kaiser, Patricia; Reinauer, Hans

    2011-01-01

    Glycated haemoglobin (HbA(1c)) measurements are used in clinical studies and for the management of diabetic patients. Various efforts were made to standardize the HbA(1c) measurements with consensus standards and standards based on a reference measurement procedure with external calibration. According to ISO 17511 a standard should meet highest accuracy possible, have a defined uncertainty of measurement and the calibration should be traceable to SI units. For HbA(1c) this has been realized using a LC-ID-MS procedure based on the existing reference measurement procedure.

  12. Stabilization of the T-state of human hemoglobin by proflavine, an antiseptic drug.

    PubMed

    Ascenzi, P; Colasanti, M; Fasano, M; Bertollini, A

    1999-06-01

    The effect of proflavine (3,6-diaminoacridine), an antiseptic drug, on the spectroscopic and oxygen binding properties of ferrous human adult hemoglobin (Hb) has been investigated. Upon binding of proflavine to the nitric oxide derivative of ferrous human adult hemoglobin (HbNO), the X-band EPR spectrum displays the characteristics which have been attributed to the T-state of the ligated tetramer. In parallel, oxygen affinity for the deoxygenated derivative of ferrous human adult Hb decreases in the presence of proflavine. The effect of proflavine on the spectroscopic and ligand binding properties of ferrous human adult Hb is reminiscent that of 2,3-D-glycerate bisphosphate, the physiological modulator of Hb action.

  13. Description of the phenotypes of 63 heterozygous, homozygous and compound heterozygous patients carrying the Hb Groene Hart [α119(H2)Pro→Ser; HBA1: c.358C>T] variant.

    PubMed

    Joly, Philippe; Lacan, Philippe; Garcia, Caroline; Francina, Alain

    2014-01-01

    We here report the phenotypes and genotypes of 63 patients of North African origin, carriers of Hb Groene Hart [Hb GH, α119(H2)Pro → Ser; HBA1: c.358C>T], an α(+)-thalassemia (α(+)-thal) hemoglobin (Hb) variant. Fifty patients were heterozygous, five were homozygous and eight also carried the common -α(3.7) (rightward) deletion in compound heterozygosity. The expression of the α(GH)-globin chain is increased in the following order: heterozygous, compound heterozygous and homozygous. Parallel significant changes of mean corpuscular Hb (MCH) and mean corpuscular volume (MCV) were also observed. Our large cohort of Hb GH carriers could have been obtained by the systematic realization of globin chain separation by reversed phase liquid chromatography (RP-LC) in our routine Hb testing.

  14. A Comparison Between the Effect of Cuminum Cyminum and Vitamin E on the Level of Leptin, Paraoxonase 1, HbA1c and Oxidized LDL in Diabetic Patients

    PubMed Central

    Samani Keihan, Ghatreh; Gharib, Mohammad Hossein; Momeni, Ali; Hemati, Zohreh; Sedighin, Roya

    2016-01-01

    Diabetes is one of the most common metabolic diseases in the world. Vitamin E reduces protein glycation and improves insulin sensitivity, while cumin is effective in remission of diabetes. Therefore this study was designed to evaluate the effects of vitamin E and cumin essential oil, on the blood level of leptin,glycosylated hemoglobin (HbA1C) and also on lipid profile in diabetic patients.In this double blind clinical trial, 95 diabetic patients were selected and randomly dividedinto three groups.The first group received cumin essential oil in capsule form. The second group received Vitamin E, and the third group was used ascontrol receiving oral gelatin capsules as placebo for three months period.Blood glucose, lipid profile, apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB), leptin, HbA1c, oxidized LDL (oxLDL), and paraoxonase1 activity were measured. The results showed reduction in oxLDL and significant increase in paraoxonase 1 in Vitamin E group by the end of the third month period (P<0.05). Cumin group showed decrease in blood glucose, HbA1C, triglyceride, leptin and ox-LDL. ApoA1 and paraoxonase1 were also increased by cumin treatment (P<0.05).Diabetic complications may have been reduced by intake of Vitamin E and cumin essential oil. Cumin in comparison with vitamin E has broader impact and it is more beneficial in terms of ability to reduce the diabetic index. PMID:28357199

  15. Lifestyle weight-loss intervention outcomes in overweight and obese adults with type 2 diabetes: a systematic review and meta-analysis of randomized clinical trials.

    PubMed

    Franz, Marion J; Boucher, Jackie L; Rutten-Ramos, Stephanie; VanWormer, Jeffrey J

    2015-09-01

    The majority of people with type 2 diabetes are overweight or obese, and weight loss is a recommended treatment strategy. A systematic review and meta-analysis was undertaken to answer the following primary question: In overweight or obese adults with type 2 diabetes, what are the outcomes on hemoglobin A1c (HbA1c) from lifestyle weight-loss interventions resulting in weight losses greater than or less than 5% at 12 months? Secondary questions are: What are the lipid (total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides) and blood pressure (systolic and diastolic) outcomes from lifestyle weight-loss interventions resulting in weight losses greater than or less than 5% at 12 months? And, what are the weight and metabolic outcomes from differing amounts of macronutrients in weight-loss interventions? Inclusion criteria included randomized clinical trial implementing weight-loss interventions in overweight or obese adults with type 2 diabetes, minimum 12-month study duration, a 70% completion rate, and an HbA1c value reported at 12 months. Eleven trials (eight compared two weight-loss interventions and three compared a weight-loss intervention group with a usual care/control group) with 6,754 participants met study criteria. At 12 months, 17 study groups (8 categories of weight-loss intervention) reported weight loss <5% of initial weight (-3.2 kg [95% CI: -5.9, -0.6]). A meta-analysis of the weight-loss interventions reported nonsignificant beneficial effects on HbA1c, lipids, or blood pressure. Two study groups reported a weight loss of ≥5%: a Mediterranean-style diet implemented in newly diagnosed adults with type 2 diabetes and an intensive lifestyle intervention implemented in the Look AHEAD (Action for Health in Diabetes) trial. Both included regular physical activity and frequent contact with health professionals and reported significant beneficial effects on HbA1c, lipids, and blood pressure. Five

  16. Hemoglobins, programmed cell death and somatic embryogenesis.

    PubMed

    Hill, Robert D; Huang, Shuanglong; Stasolla, Claudio

    2013-10-01

    Programmed cell death (PCD) is a universal process in all multicellular organisms. It is a critical component in a diverse number of processes ranging from growth and differentiation to response to stress. Somatic embryogenesis is one such process where PCD is significantly involved. Nitric oxide is increasingly being recognized as playing a significant role in regulating PCD in both mammalian and plant systems. Plant hemoglobins scavenge NO, and evidence is accumulating that events that modify NO levels in plants also affect hemoglobin expression. Here, we review the process of PCD, describing the involvement of NO and plant hemoglobins in the process. NO is an effector of cell death in both plants and vertebrates, triggering the cascade of events leading to targeted cell death that is a part of an organism's response to stress or to tissue differentiation and development. Expression of specific hemoglobins can alter this response in plants by scavenging the NO, thus, interrupting the death process. Somatic embryogenesis is used as a model system to demonstrate how cell-specific expression of different classes of hemoglobins can alter the embryogenic process, affecting hormone synthesis, cell metabolite levels and genes associated with PCD and embryogenic competence. We propose that plant hemoglobins influence somatic embryogenesis and PCD through cell-specific expression of a distinct plant hemoglobin. It is based on the premise that both embryogenic competence and PCD are strongly influenced by cellular NO levels. Increases in cellular NO levels result in elevated Zn(2+) and reactive-oxygen species associated with PCD, but they also result in decreased expression of MYC2, a transcription factor that is a negative effector of indoleacetic acid synthesis, a hormone that positively influences embryogenic competence. Cell-specific hemoglobin expression reduces NO levels as a result of NO scavenging, resulting in cell survival.

  17. Cloned Hemoglobin Genes Enhance Growth Of Cells

    NASA Technical Reports Server (NTRS)

    Khosla, Chaitan; Bailey, James E.

    1991-01-01

    Experiments show that portable deoxyribonucleic acid (DNA) sequences incorporated into host cells make them produce hemoglobins - oxygen-binding proteins essential to function of red blood cells. Method useful in several biotechnological applications. One, enhancement of growth of cells at higher densities. Another, production of hemoglobin to enhance supplies of oxygen in cells, for use in chemical reactions requiring oxygen, as additive to serum to increase transport of oxygen, and for binding and separating oxygen from mixtures of gases.

  18. Carboxyalkylated Hemoglobin as a Potential Blood Substitute.

    DTIC Science & Technology

    1991-11-19

    diisothiocyanatobenzene sulfonic acid. Collaborative studies with investigators at the Letterman Army Institute of Research indicated that carboxy - methylated hemoglobin... crosslinking agents so that we might find the one with the most desirable properties (2,3). In this annual report, we focus on the reagents studied in...can be considered as a mimic for both of these structures. Crosslinking of Hemoglobin A - In the past year we have sought a better crosslinking agent

  19. Hemoglobin parameters from diffuse reflectance data.

    PubMed

    Mourant, Judith R; Marina, Oana C; Hebert, Tiffany M; Kaur, Gurpreet; Smith, Harriet O

    2014-03-01

    Tissue vasculature is altered when cancer develops. Consequently, noninvasive methods of monitoring blood vessel size, density, and oxygenation would be valuable. Simple spectroscopy employing fiber optic probes to measure backscattering can potentially determine hemoglobin parameters. However, heterogeneity of blood distribution, the dependence of the tissue-volume-sampled on scattering and absorption, and the potential compression of tissue all hinder the accurate determination of hemoglobin parameters. We address each of these issues. A simple derivation of a correction factor for the absorption coefficient, μa, is presented. This correction factor depends not only on the vessel size, as others have shown, but also on the density of blood vessels. Monte Carlo simulations were used to determine the dependence of an effective pathlength of light through tissue which is parameterized as a ninth-order polynomial function of μa. The hemoglobin bands of backscattering spectra of cervical tissue are fit using these expressions to obtain effective blood vessel size and density, tissue hemoglobin concentration, and oxygenation. Hemoglobin concentration and vessel density were found to depend on the pressure applied during in vivo acquisition of the spectra. It is also shown that determined vessel size depends on the blood hemoglobin concentration used.

  20. Noninvasive hemoglobin monitoring: how accurate is enough?

    PubMed

    Rice, Mark J; Gravenstein, Nikolaus; Morey, Timothy E

    2013-10-01

    Evaluating the accuracy of medical devices has traditionally been a blend of statistical analyses, at times without contextualizing the clinical application. There have been a number of recent publications on the accuracy of a continuous noninvasive hemoglobin measurement device, the Masimo Radical-7 Pulse Co-oximeter, focusing on the traditional statistical metrics of bias and precision. In this review, which contains material presented at the Innovations and Applications of Monitoring Perfusion, Oxygenation, and Ventilation (IAMPOV) Symposium at Yale University in 2012, we critically investigated these metrics as applied to the new technology, exploring what is required of a noninvasive hemoglobin monitor and whether the conventional statistics adequately answer our questions about clinical accuracy. We discuss the glucose error grid, well known in the glucose monitoring literature, and describe an analogous version for hemoglobin monitoring. This hemoglobin error grid can be used to evaluate the required clinical accuracy (±g/dL) of a hemoglobin measurement device to provide more conclusive evidence on whether to transfuse an individual patient. The important decision to transfuse a patient usually requires both an accurate hemoglobin measurement and a physiologic reason to elect transfusion. It is our opinion that the published accuracy data of the Masimo Radical-7 is not good enough to make the transfusion decision.

  1. 21 CFR 864.7415 - Abnormal hemoglobin assay.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Abnormal hemoglobin assay. 864.7415 Section 864... hemoglobin assay. (a) Identification. An abnormal hemoglobin assay is a device consisting of the reagents... hemoglobin types. (b) Classification. Class II (performance standards)....

  2. 21 CFR 864.7415 - Abnormal hemoglobin assay.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Abnormal hemoglobin assay. 864.7415 Section 864... hemoglobin assay. (a) Identification. An abnormal hemoglobin assay is a device consisting of the reagents... hemoglobin types. (b) Classification. Class II (performance standards)....

  3. 21 CFR 866.5470 - Hemoglobin immunological test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Hemoglobin immunological test system. 866.5470... Hemoglobin immunological test system. (a) Indentification. A hemoglobin immunological test system is a device... hemoglobin (the oxygen-carrying pigment in red blood cells) in blood, urine, plasma, or other body...

  4. 21 CFR 864.5620 - Automated hemoglobin system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Automated hemoglobin system. 864.5620 Section 864....5620 Automated hemoglobin system. (a) Identification. An automated hemoglobin system is a fully... hemoglobin content of human blood. (b) Classification. Class II (performance standards)....

  5. 21 CFR 864.7500 - Whole blood hemoglobin assays.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Whole blood hemoglobin assays. 864.7500 Section... blood hemoglobin assays. (a) Identification. A whole blood hemoglobin assay is a device consisting or... hemoglobin content of whole blood for the detection of anemia. This generic device category does not...

  6. 21 CFR 864.7415 - Abnormal hemoglobin assay.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Abnormal hemoglobin assay. 864.7415 Section 864... hemoglobin assay. (a) Identification. An abnormal hemoglobin assay is a device consisting of the reagents... hemoglobin types. (b) Classification. Class II (performance standards)....

  7. 21 CFR 864.5620 - Automated hemoglobin system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Automated hemoglobin system. 864.5620 Section 864....5620 Automated hemoglobin system. (a) Identification. An automated hemoglobin system is a fully... hemoglobin content of human blood. (b) Classification. Class II (performance standards)....

  8. 21 CFR 864.7500 - Whole blood hemoglobin assays.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Whole blood hemoglobin assays. 864.7500 Section... blood hemoglobin assays. (a) Identification. A whole blood hemoglobin assay is a device consisting or... hemoglobin content of whole blood for the detection of anemia. This generic device category does not...

  9. 21 CFR 864.7440 - Electrophoretic hemoglobin analysis system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Electrophoretic hemoglobin analysis system. 864....7440 Electrophoretic hemoglobin analysis system. (a) Identification. An electrophoretic hemoglobin... hemoglobin types as an aid in the diagnosis of anemia or erythrocytosis (increased total red cell mass)...

  10. 21 CFR 864.7440 - Electrophoretic hemoglobin analysis system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Electrophoretic hemoglobin analysis system. 864....7440 Electrophoretic hemoglobin analysis system. (a) Identification. An electrophoretic hemoglobin... hemoglobin types as an aid in the diagnosis of anemia or erythrocytosis (increased total red cell mass)...

  11. 21 CFR 864.5620 - Automated hemoglobin system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Automated hemoglobin system. 864.5620 Section 864....5620 Automated hemoglobin system. (a) Identification. An automated hemoglobin system is a fully... hemoglobin content of human blood. (b) Classification. Class II (performance standards)....

  12. 21 CFR 864.7500 - Whole blood hemoglobin assays.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Whole blood hemoglobin assays. 864.7500 Section... blood hemoglobin assays. (a) Identification. A whole blood hemoglobin assay is a device consisting or... hemoglobin content of whole blood for the detection of anemia. This generic device category does not...

  13. 21 CFR 864.7440 - Electrophoretic hemoglobin analysis system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Electrophoretic hemoglobin analysis system. 864....7440 Electrophoretic hemoglobin analysis system. (a) Identification. An electrophoretic hemoglobin... hemoglobin types as an aid in the diagnosis of anemia or erythrocytosis (increased total red cell mass)...

  14. 21 CFR 864.5620 - Automated hemoglobin system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Automated hemoglobin system. 864.5620 Section 864....5620 Automated hemoglobin system. (a) Identification. An automated hemoglobin system is a fully... hemoglobin content of human blood. (b) Classification. Class II (performance standards)....

  15. 21 CFR 864.7440 - Electrophoretic hemoglobin analysis system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Electrophoretic hemoglobin analysis system. 864....7440 Electrophoretic hemoglobin analysis system. (a) Identification. An electrophoretic hemoglobin... hemoglobin types as an aid in the diagnosis of anemia or erythrocytosis (increased total red cell mass)...

  16. 21 CFR 866.5470 - Hemoglobin immunological test system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Hemoglobin immunological test system. 866.5470... Hemoglobin immunological test system. (a) Indentification. A hemoglobin immunological test system is a device... hemoglobin (the oxygen-carrying pigment in red blood cells) in blood, urine, plasma, or other body...

  17. 21 CFR 866.5470 - Hemoglobin immunological test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Hemoglobin immunological test system. 866.5470... Hemoglobin immunological test system. (a) Indentification. A hemoglobin immunological test system is a device... hemoglobin (the oxygen-carrying pigment in red blood cells) in blood, urine, plasma, or other body...

  18. 21 CFR 864.5620 - Automated hemoglobin system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Automated hemoglobin system. 864.5620 Section 864....5620 Automated hemoglobin system. (a) Identification. An automated hemoglobin system is a fully... hemoglobin content of human blood. (b) Classification. Class II (performance standards)....

  19. 21 CFR 864.7415 - Abnormal hemoglobin assay.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Abnormal hemoglobin assay. 864.7415 Section 864... hemoglobin assay. (a) Identification. An abnormal hemoglobin assay is a device consisting of the reagents... hemoglobin types. (b) Classification. Class II (performance standards)....

  20. 21 CFR 864.7500 - Whole blood hemoglobin assays.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Whole blood hemoglobin assays. 864.7500 Section... blood hemoglobin assays. (a) Identification. A whole blood hemoglobin assay is a device consisting or... hemoglobin content of whole blood for the detection of anemia. This generic device category does not...

  1. 21 CFR 866.5470 - Hemoglobin immunological test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Hemoglobin immunological test system. 866.5470... Hemoglobin immunological test system. (a) Indentification. A hemoglobin immunological test system is a device... hemoglobin (the oxygen-carrying pigment in red blood cells) in blood, urine, plasma, or other body...

  2. 21 CFR 864.7500 - Whole blood hemoglobin assays.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Whole blood hemoglobin assays. 864.7500 Section... blood hemoglobin assays. (a) Identification. A whole blood hemoglobin assay is a device consisting or... hemoglobin content of whole blood for the detection of anemia. This generic device category does not...

  3. 21 CFR 864.7415 - Abnormal hemoglobin assay.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Abnormal hemoglobin assay. 864.7415 Section 864... hemoglobin assay. (a) Identification. An abnormal hemoglobin assay is a device consisting of the reagents... hemoglobin types. (b) Classification. Class II (performance standards)....

  4. 21 CFR 864.7440 - Electrophoretic hemoglobin analysis system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Electrophoretic hemoglobin analysis system. 864....7440 Electrophoretic hemoglobin analysis system. (a) Identification. An electrophoretic hemoglobin... hemoglobin types as an aid in the diagnosis of anemia or erythrocytosis (increased total red cell mass)...

  5. Glycated hemoglobin is not an accurate indicator of glycemia in rainbow trout.

    PubMed

    Santin, A E; Searle, A J; Winston, V D; Powell, M S; Hardy, R W; Rodnick, K J

    2013-07-01

    Glycation occurs when glucose reacts non-enzymatically with proteins. This reaction depends upon time, ambient glucose concentration, and the molecular conformation of reactive amino acids. Little is known about protein glycation in fishes and the main objective of this study was to measure glycated hemoglobin (GHb) in rainbow trout, a glucose-intolerant species, under normoglycemic and hyperglycemic conditions. We also identified GHb isoforms in vivo and analyzed the structural environment surrounding potential glycation sites. Despite similar glycemia to healthy humans, GHb was an order of magnitude lower in rainbow trout (0.6%) compared with humans (6%) and was not affected by long-term hyperglycemia. Species differences in GHb appear to be related to differences in erythrocyte glucose, and differential expression and glycation of hemoglobin (Hb) isoforms may explain intraspecific differences in rainbow trout GHb. Computer analysis of glucose isomers (ringed-open and α- and β-pyranoses) interacting with the β-chain of rainbow trout HbI and HbIV, and human HbA did not reveal structural or energetic constraints for glucose binding (the initial step of glycation) for rainbow trout Hbs. Overall, there are significant differences between Hb glycation in humans and rainbow trout, and GHb does not appear to be an accurate indicator of glycemia over time in rainbow trout.

  6. Mutual effects of proton and sodium chloride on oxygenation of liganded human hemoglobin.

    PubMed

    Lepeshkevich, Sergei V; Dzhagarov, Boris M

    2005-12-01

    The different effects of pH and NaCl on individual O2-binding properties of alpha and beta subunits within liganded tetramer and dimer of human hemoglobin (HbA) were examined in a number of laser time-resolved spectroscopic measurements. A previously proposed approach [Dzhagarov BM & Lepeshkevich SV (2004) Chem Phys Lett390, 59-64] was used to determine the extent of subunit dissociation rate constant difference and subunit affinity difference from a single flash photolysis experiment. To investigate the effect of NaCl concentration on the association and dissociation rate constants we carried out a series of experiments at four different concentrations (0.1, 0.5, 1.0 and 2.0 m NaCl) over the pH range of the alkaline Bohr effect. As the data suggest, the individual properties of the alpha and beta subunits within the completely liganded tetrameric hemoglobin did not depend on pH under salt-free conditions. However, different effects NaCl on the individual kinetic properties of the alpha and beta subunits were revealed. Regulation of the O2-binding properties of the alpha and beta subunits within the liganded tetramer is proposed to be attained in two quite different ways.

  7. Phase Separation and Crystallization of Hemoglobin C in Transgenic Mouse and Human Erythrocytes

    PubMed Central

    Canterino, Joseph E.; Galkin, Oleg; Vekilov, Peter G.; Hirsch, Rhoda Elison

    2008-01-01

    Individuals expressing hemoglobin C (β6 Glu→Lys) present red blood cells (RBC) with intraerythrocytic crystals that form when hemoglobin (Hb) is oxygenated. Our earlier in vitro liquid-liquid (L-L) phase separation studies demonstrated that liganded HbC exhibits a stronger net intermolecular attraction with a longer range than liganded HbS or HbA, and that L-L phase separation preceded and enhanced crystallization. We now present evidence for the role of phase separation in HbC crystallization in the RBC, and the role of the RBC membrane as a nucleation center. RBC obtained from both human homozygous HbC patients and transgenic mice expressing only human HbC were studied by bright-field and differential interference contrast video-enhanced microscopy. RBC were exposed to hypertonic NaCl solution (1.5–3%) to induce crystallization within an appropriate experimental time frame. L-L phase separation occurred inside the RBC, which in turn enhanced the formation of intraerythrocytic crystals. RBC L-L phase separation and crystallization comply with the thermodynamic and kinetics laws established through in vitro studies of phase transformations. This is the first report, to the best of our knowledge, to capture a temporal view of intraerythrocytic HbC phase separation, crystal formation, and dissolution. PMID:18621841

  8. Tangential flow filtration of hemoglobin.

    PubMed

    Palmer, Andre F; Sun, Guoyong; Harris, David R

    2009-01-01

    Bovine and human hemoglobin (bHb and hHb, respectively) was purified from bovine and human red blood cells via tangential flow filtration (TFF) in four successive stages. TFF is a fast and simple method to purify Hb from RBCs using filtration through hollow fiber (HF) membranes. Most of the Hb was retained in stage III (100 kDa HF membrane) and displayed methemoglobin levels less than 1%, yielding final concentrations of 318 and 300 mg/mL for bHb and hHb, respectively. Purified Hb exhibited much lower endotoxin levels than their respective RBCs. The purity of Hb was initially assessed via SDS-PAGE, and showed tiny impurity bands for the stage III retentate. The oxygen affinity (P(50)) and cooperativity coefficient (n) were regressed from the measured oxygen-RBC/Hb equilibrium curves of RBCs and purified Hb. These results suggest that TFF yielded oxygen affinities of bHb and hHb that are comparable to values in the literature. LC-MS was used to measure the molecular weight of the alpha (alpha) and beta (beta) globin chains of purified Hb. No impurity peaks were present in the HPLC chromatograms of purified Hb. The mass of the molecular ions corresponding to the alpha and beta globin chains agreed well with the calculated theoretical mass of the alpha- and beta- globin chains. Taken together, our results demonstrate that HPLC-grade Hb can be generated via TFF. In general, this method can be more broadly applied to purify Hb from any source of RBCs. This work is significant, since it outlines a simple method for generating Hb for synthesis and/or formulation of Hb-based oxygen carriers.

  9. Measurement of HbA1c from stored whole blood samples in the Atherosclerosis Risk in Communities study

    PubMed Central

    SELVIN, Elizabeth; CORESH, Josef; ZHU, Hong; FOLSOM, Aaron; STEFFES, Michael W.

    2010-01-01

    Background The aims of the present study were to demonstrate the reliability of HbA1c measurements across two time periods and to compare these measurements with HbA1c distribution in the general US population. Methods HbA1c was measured in 14 069 whole blood samples in the Atherosclerosis Risk in Communities (ARIC) study using different HPLC instruments during two time periods, namely 2003–2004 and 2007–2008. At the time of measurement, samples had been in storage at –70°C for 14–18 years. To assess differences in values, HbA1c measurements were repeated in 383 samples at both periods. Indirect comparisons were made by comparing our measurements against those from a nationally representative study. Results The coefficients of variation for quality control samples were 1.8% (n = 89) in 2003–2004 and 1.4% (n = 259) in 2007–2008. The correlation between measurements at the two time points was high (r = 0.99), but with a slight bias: 0.29% points higher in 2007–2008 versus 2003–2004 (n = 383; P < 0.0001). The comparison yielded the following Deming regression equation: y(2007–2008) = 0.073+1.034x(2003–2004). After alignment using this equation, the distribution of HbA1c in the ARIC study was similar to that in the national study using fresh samples. Conclusions Measurements of HbA1c from samples stored for 14–18 years are highly reliable when using state-of-the-art HPLC instruments, but with some bias introduced over time. The HbA1c data now available in the ARIC study should be invaluable for investigations into the clinical utility of HbA1c as a diagnostic test for diabetes. PMID:20923494

  10. HbA1c for the diagnosis of diabetes mellitus in a developing country. A position article.

    PubMed

    Gomez-Perez, Francisco J; Aguilar-Salinas, Carlos A; Almeda-Valdes, Paloma; Cuevas-Ramos, Daniel; Lerman Garber, Israel; Rull, Juan A

    2010-05-01

    An Expert Committee of the American Diabetes Association and the European Association for the Study of Diabetes recommended a move to the use of HbA1c level to diagnose diabetes mellitus. Diagnosis should be made if the A1c level is > or = 6.5%. HbA1c provides a reliable measure of chronic glycemia, correlates well with the risk of long-term diabetes complications and technical limitations for standardization have been overcome in laboratories of the U.S. and Europe. The objective of this paper is to analyze critically the advantages and disadvantages of the use of HbA1c as a diagnostic method of diabetes in a developing country. The lack of a universal threshold for the diagnosis of diabetes, the cost of the test and the absence of the standardization network in the majority of the countries are major arguments for not including HbA1c as diagnostic criteria of diabetes. HbA1c diagnostic criteria has a low sensitivity. As a result, there is a lack of agreement between the HbA1c criteria with the other diagnostic methods that lead into significant variations in the number of affected cases. In addition, sensitivity and specificity vary among ethnic groups. No study has compared the diagnostic properties of the HbA1c in Latin America. In conclusion, the logistic limitations that exist in a large proportion of developing countries and the unsolved uncertainties that exist for the definition of the A1c criterion are strong arguments against the inclusion of HbA1c among the diagnostic criteria of diabetes.

  11. Effects of Qigong Exercise on Biomarkers and Mental and Physical Health in Adults With at Least One Risk Factor for Coronary Artery Disease.

    PubMed

    Hung, Hsuan-Man; Yeh, Shu-Hui; Chen, Chung-Hey

    2016-05-01

    Current medical technology permits the early detection of risk factors for coronary artery disease (CAD) in adults, and interventions are available to prevent CAD-related morbidity and mortality. The goal of this study was to determine the effectiveness of a Qigong exercise intervention in improving biomarker levels and mental and physical health outcomes in community-dwelling adults diagnosed with CAD risk factors, in a southern Taiwanese city. Participants were randomly assigned to an experimental (n= 84) group that participated in a 60-min Qigong group session 3 times per week for 3 months or a control (n= 61) group that did not receive the intervention. Self-perceived mental and physical health assessed with the Chinese Health Questionnaire-12, and body fat percentage were measured at baseline and 6, 12, and 16 weeks. Blood samples were collected at baseline and 12 weeks for analysis of lipid profiles, high-sensitivity C-reactive protein (hs-CRP), glycated hemoglobin (HbA1c), and fasting plasma sugar. Linear mixed model analyses revealed that experimental participants had significantly improved perceived mental and physical health and body fat percentage compared to the control group at 6 and 12 weeks but not 16 weeks. The lipid profiles were significantly more improved in the Qigong group than in the control group at 12 weeks. Qigong exercise, however, had no significant effects on hs-CRP, HbA1c, or fasting plasma sugar. Findings suggest that Qigong exercise improves a limited number of CAD risk factors in community-dwelling adults aged 40 years and over.

  12. Risk of Type 2 Diabetes Is Lower in US Adults Taking Chromium-Containing Supplements123

    PubMed Central

    McIver, David J; Grizales, Ana Maria; Brownstein, John S; Goldfine, Allison B

    2015-01-01

    Background: Dietary supplement use is widespread in the United States. Although it has been suggested in both in vitro and small in vivo human studies that chromium has potentially beneficial effects in type 2 diabetes (T2D), chromium supplementation in diabetes has not been investigated at the population level. Objective: The objective of this study was to examine the use and potential benefits of chromium supplementation in T2D by examining NHANES data. Methods: An individual was defined as having diabetes if he or she had a glycated hemoglobin (HbA1c) value of ≥6.5%, or reported having been diagnosed with diabetes. Data on all consumed dietary supplements from the NHANES database were analyzed, with the OR of having diabetes as the main outcome of interest based on chromium supplement use. Results: The NHANES for the years 1999–2010 included information on 62,160 individuals. After filtering the database for the required covariates (gender, ethnicity, socioeconomic status, body mass index, diabetes diagnosis, supplement usage, and laboratory HbA1c values), and when restricted to adults, the study cohort included 28,539 people. A total of 58.3% of people reported consuming a dietary supplement in the previous 30 d, 28.8% reported consuming a dietary supplement that contained chromium, and 0.7% consumed supplements that had “chromium” in the title. Compared with nonusers, the odds of having T2D (HbA1c ≥6.5%) were lower in persons who consumed chromium-containing supplements within the previous 30 d than in those who did not (OR: 0.73; 95% CI: 0.62, 0.86; P = 0.001). Supplement use alone (without chromium) did not influence the odds of having T2D (OR: 0.89; 95% CI: 0.77, 1.03; P = 0.11). Conclusions: Over one-half the adult US population consumes nutritional supplements, and over one-quarter consumes supplemental chromium. The odds of having T2D were lower in those who, in the previous 30 d, had consumed supplements containing chromium. Given the

  13. Association between HbA1c and carotid atherosclerosis among elderly Koreans with normal fasting glucose

    PubMed Central

    Lee, Seung Won; Kim, Hyeon Chang; Lee, Yong-ho; Song, Bo Mi; Choi, Hansol; Park, Ji Hye; Rhee, Yumie; Kim, Chang Oh

    2017-01-01

    Aim We examined whether glycated haemoglobin (HbA1c) is associated to carotid atherosclerosis in an elderly Korean population with normal fasting glucose. Methods Using data from the Korean Urban Rural Elderly study, we conducted a cross-sectional analysis of 1,133 participants (335 men and 798 women) with a mean age of 71.8 years. All participants had fasting blood glucose less than 100mg/dL (5.6 mmol/L) and HbA1c level below 6.5% (48 mmol/mol). They were also free from a history of cardiovascular disease, known type 2 diabetes mellitus or use of anti-diabetes medications. Carotid atherosclerosis was assessed by intima-media thickness (IMT) using ultrasonography. The association between HbA1c and carotid IMT was investigated using multivariable linear regression analysis. Results HbA1c levels were independently and positively associated with carotid IMT (β = 0.020, p = 0.045) after adjusting for sex, age, body mass index, systolic blood pressure, diastolic blood pressure, triglyceride, LDL cholesterol, smoking and alcohol intake. However, fasting insulin and glucose levels were not associated with carotid IMT. Conclusion HbA1c levels were positively associated with carotid atherosclerosis, as assessed by carotid IMT, in an elderly population with normoglycemia. Our study suggested that higher HbA1c level is an effective and informative marker of carotid atherosclerosis in an elderly population. PMID:28178313

  14. Effect of the systemic inflammatory response, as provoked by elective orthopaedic surgery, on HbA1c.

    PubMed

    Chadburn, Andrew J; Garman, Elizabeth; Abbas, Raad; Modupe, Anu; Ford, Clare; Thomas, Osmond L; Chugh, Sanjiv; Deshpande, Shreeram; Gama, Rousseau

    2017-01-01

    Background In acutely ill patients with new onset hyperglycaemia, plasma glucose cannot reliably distinguish between stress hyperglycaemia and undiagnosed diabetes mellitus. We, therefore, investigated the diagnostic reliability of glycated haemoglobin (HbA1c) in acute illness by prospectively evaluating the effect of the systemic inflammatory response, as provoked by elective orthopaedic surgery, on HbA1c. Methods HbA1c and serum C-reactive protein concentrations were compared before and two days after elective knee or hip surgery in 30 patients without diabetes. C-reactive protein was used to assess the systemic inflammatory response. Results The mean (standard deviation) serum C-reactive protein increased following surgery (4.8 [7.5] vs. 179.7 [61.9] mg/L; P<0.0001). HbA1c was similar before and after surgery (39.2 [5.4] vs. 38.1 [5.1] mmol/moL, respectively; P = 0.4363). Conclusions HbA1c is unaffected within two days of a systemic inflammatory response as provoked by elective orthopaedic surgery. This suggests that HbA1c may be able to differentiate newly presenting type 2 diabetes mellitus from stress hyperglycaemia in acutely ill patients with new onset hyperglycaemia.

  15. Polyethylene Glycol Camouflaged Earthworm Hemoglobin

    PubMed Central

    Moges, Selamawit; Nacharaju, Parimala; Roche, Camille; Dantsker, David; Palmer, Andre; Friedman, Joel M.

    2017-01-01

    Nearly 21 million components of blood and whole blood and transfused annually in the United States, while on average only 13.6 million units of blood are donated. As the demand for Red Blood Cells (RBCs) continues to increase due to the aging population, this deficit will be more significant. Despite decades of research to develop hemoglobin (Hb) based oxygen (O2) carriers (HBOCs) as RBC substitutes, there are no products approved for clinical use. Lumbricus terrestris erythrocruorin (LtEc) is the large acellular O2 carrying protein complex found in the earthworm Lumbricus terrestris. LtEc is an extremely stable protein complex, resistant to autoxidation, and capable of transporting O2 to tissue when transfused into mammals. These characteristics render LtEc a promising candidate for the development of the next generation HBOCs. LtEc has a short half-life in circulation, limiting its application as a bridge over days, until blood became available. Conjugation with polyethylene glycol (PEG-LtEc) can extend LtEc circulation time. This study explores PEG-LtEc pharmacokinetics and pharmacodynamics. To study PEG-LtEc pharmacokinetics, hamsters instrumented with the dorsal window chamber were subjected to a 40% exchange transfusion with 10 g/dL PEG-LtEc or LtEc and followed for 48 hours. To study the vascular response of PEG-LtEc, hamsters instrumented with the dorsal window chamber received multiple infusions of 10 g/dL PEG-LtEc or LtEc solution to increase plasma LtEc concentration to 0.5, then 1.0, and 1.5 g/dL, while monitoring the animals’ systemic and microcirculatory parameters. Results confirm that PEGylation of LtEc increases its circulation time, extending the half-life to 70 hours, 4 times longer than that of unPEGylated LtEc. However, PEGylation increased the rate of LtEc oxidation in vivo. Vascular analysis verified that PEG-LtEc showed the absence of microvascular vasoconstriction or systemic hypertension. The molecular size of PEG-LtEc did not change the

  16. Effects of polymerization on the oxygen carrying and redox properties of diaspirin cross-linked hemoglobin.

    PubMed

    Rogers, M S; Ryan, B B; Cashon, R E; Alayash, A I

    1995-04-27

    Human hemoglobin site specifically cross-linked with bis(3,5-dibromosalicyl)fumarate results in a low oxygen affinity hemoglobin-based red cell substitute (alpha-DBBF). Polymerization of alpha-DBBF by bis(maleoylglycylamide) polyethylene glycol (BMAA-PEG) yields poly alpha-DBBF which offers the added benefits of reduced renal clearance and increased retention in the vascular circulation. Oxygen equilibrium curves for poly alpha-DBBF are slightly left-shifted (higher O2 affinity) compared to those of alpha-DBBF; with a diminished cooperativity and a reduced Bohr effect. In rapid mixing experiments (oxygen dissociation and carbon monoxide binding), poly alpha-DBBF exhibits a several fold increase in the overall rate of deoxygenation and carbon monoxide binding kinetics over its cross-linked counterpart. The rate of nitric oxide binding to the oxidized form of poly alpha-DBBF shows little or no change compared to the intramolecularly cross-linked derivative. The reduction of cyanomet poly alpha-DBBF by dithionite is several fold faster than that of HbA0 and alpha-DBBF whereas the slow subsequent cyanide dissociation from the ferrous iron remained unchanged among all proteins. The propensity of poly alpha-DBBF for auto-oxidation is slightly enhanced over alpha-DBBF whereas the extent of oxidative modification by hydrogen peroxide is very similar. Polymerization appears to selectively modify ligand interactions and redox kinetics of the tetrameric cross-linked form which reflects a possibly more open heme pocket. The data suggests that changes in oxygenation properties of hemoglobin brought about by a given modification are not necessarily predictive of other functional changes.

  17. The effect of gamma-rays on the hemoglobin of whole-body irradiated mice

    NASA Astrophysics Data System (ADS)

    Ashry, H. A.; Selim, N. S.; El-Behay, A. Z.

    1994-07-01

    Changes in the UV-visible absorption spectrum of mouse hemoglobin as a result of whole body irradiation were studied. White albino adult mice were exposed to a Cs-137 γ-source at a dose rate of 47.5 Gy/h to different absorbed dose values ranging from 1 to 8 Gy. Blood specimens were taken 24 h after irradiation. The UV-visible absorption spectra of hemoglobin of irradiated and control mice were measured in the wavelength range from 200 to 700 nm. The obtained results showed significant changes in the bands measured at 340 nm, in the Soret band measured at 410 nm, also, the α- and β-bands measured at 537 and 572 nm showed significant decrease in intensity with the absorbed dose increase. The absorbance measured at 630 nm showed no significant changes. The radiation effect on the animal hemoglobin was discussed on the basis of the obtained results.

  18. Cytokine profiling of young overweight and obese female African American adults with prediabetes.

    PubMed

    Lucas, Rudolf; Parikh, Samip J; Sridhar, Supriya; Guo, De-Huang; Bhagatwala, Jigar; Dong, Yutong; Caldwell, Ruth; Mellor, Andrew; Caldwell, William; Zhu, Haidong; Dong, Yanbin

    2013-10-01

    Approximately 5-10% of subjects with prediabetes become diabetic every year. Inflammation is involved in the development of obesity-related type 2 diabetes (T2D). However, to date, the relationship between inflammation and prediabetes, defined by hemoglobin A1c (HbA1c) ≥5.7 and <6.5%, remains largely unexplored, especially in African Americans. Therefore, in this study we examined a comprehensive panel of 13 cytokines involved in the inflammatory response in overweight/obese subjects with prediabetes. A total of 21 otherwise healthy, overweight/obese, young adult African American females with prediabetes, together with 20 matched overweight/obese controls, were selected for this study. Plasma cytokines were assessed by multiplex cytokine profiling. Plasma concentrations of interleukin (IL)-5, IL-6, IL-7, tumor necrosis factor-α (TNF-α), and granulocyte-monocyte colony-stimulating factor (GM-CSF) were significantly higher in the prediabetic group, as compared to the control group (all p<0.05). Plasma concentrations of all the other cytokines, interferon-γ (IFN-γ), IL-1β, IL-2, IL-4, IL-8, IL-10, IL-12p70 and IL-13, seemed to be elevated in the prediabetic group, but failed to reach statistical significances. Upon merging both groups, HbA1c was found to be positively correlated with IFN-γ, IL-1β, IL-2, IL-5, IL-7, IL-8, TNF-α and GM-CSF. This study demonstrates elevated levels of various pro-inflammatory cytokines in overweight/obese young subjects with prediabetes, which place them at higher risk of developing T2D and cardiovascular diseases. Our data also call for further investigations in animal models and population cohorts to establish the roles of a variety of pro-inflammatory cytokines in the early development of obesity-related T2D.

  19. Comparison of admission random glucose, fasting glucose, and glycated hemoglobin in predicting the neurological outcome of acute ischemic stroke: a retrospective study

    PubMed Central

    Sung, Jia-Ying; Chen, Chin-I; Hsieh, Yi-Chen; Chen, Yih-Ru; Wu, Hsin-Chiao; Chan, Lung; Hu, Chaur-Jong; Hu, Han-Hwa; Chiou, Hung-Yi

    2017-01-01

    Background Hyperglycemia is a known predictor of negative outcomes in stroke. Several glycemic measures, including admission random glucose, fasting glucose, and glycated hemoglobin (HbA1c), have been associated with bad neurological outcomes in acute ischemic stroke, particularly in nondiabetic patients. However, the predictive power of these glycemic measures is yet to be investigated. Methods This retrospective study enrolled 484 patients with acute ischemic stroke from January 2009 to March 2013, and complete records of initial stroke severity, neurological outcomes at three months, and glycemic measures were evaluated. We examined the predictive power of admission random glucose, fasting glucose, and HbA1c for neurological outcomes in acute ischemic stroke. Furthermore, subgroup analyses of nondiabetic patients and patients with diabetes were performed separately. Results Receiver operating characteristic (ROC) analysis revealed that admission random glucose and fasting glucose were significant predictors of poor neurological outcomes, whereas HbA1c was not (areas under the ROC curve (AUCs): admission random glucose = 0.564, p = 0.026; fasting glucose = 0.598, p = 0.001; HbA1c = 0.510, p = 0.742). Subgroup analyses of nondiabetic patients and those with diabetes revealed that only fasting glucose predicts neurological outcomes in patients with diabetes, and the AUCs of these three glycemic measures did not differ between the two groups. A multivariate logistic regression analysis of the study patients indicated that only age, initial stroke severity, and fasting glucose were independent predictors of poor neurological outcomes, whereas admission random glucose and HbA1c were not (adjusted odds ratio: admission random glucose = 1.002, p = 0.228; fasting glucose = 1.005, p = 0.039; HbA1c = 1.160, p = 0.076). Furthermore, subgroup multivariate logistic regression analyses of nondiabetic patients and those with diabetes indicated that none of the three glycemic

  20. Hemoglobin genetics: recent contributions of GWAS and gene editing.

    PubMed

    Smith, Elenoe C; Orkin, Stuart H

    2016-10-01

    The β-hemoglobinopathies are inherited disorders resulting from altered coding potential or expression of the adult β-globin gene. Impaired expression of β-globin reduces adult hemoglobin (α2β2) production, the hallmark of β-thalassemia. A single-base mutation at codon 6 leads to formation of HbS (α2β(S)2) and sickle cell disease. While the basis of these diseases is known, therapy remains largely supportive. Bone marrow transplantation is the only curative therapy. Patients with elevated levels of fetal hemoglobin (HbF, α2γ2) as adults exhibit reduced symptoms and enhanced survival. The β-globin gene locus is a paradigm of cell- and developmental stage-specific regulation. Although the principal erythroid cell transcription factors are known, mechanisms responsible for silencing of the γ-globin gene were obscure until application of genome-wide association studies (GWAS). Here, we review findings in the field. GWAS identified BCL11A as a candidate negative regulator of γ-globin expression. Subsequent studies have established BCL11A as a quantitative repressor. GWAS-related single-nucleotide polymorphisms lie within an essential erythroid enhancer of the BCL11A gene. Disruption of a discrete region within the enhancer reduces BCL11A expression and induces HbF expression, providing the basis for gene therapy using gene editing tools. A recently identified, second silencing factor, leukemia/lymphoma-related factor/Pokemon, shares features with BCL11A, including interaction with the nucleosome remodeling deacetylase repressive complex. These findings suggest involvement of a common pathway for HbF silencing. In addition, we discuss other factors that may be involved in γ-globin gene silencing and their potential manipulation for therapeutic benefit in treating the β-hemoglobinopathies.

  1. Classification of the Disorders of Hemoglobin

    PubMed Central

    Forget, Bernard G.; Bunn, H. Franklin

    2013-01-01

    Over the years, study of the disorders of hemoglobin has served as a paradigm for gaining insights into the cellular and molecular biology, as well as the pathophysiology, of inherited genetic disorders. To date, more than 1000 disorders of hemoglobin synthesis and/or structure have been identified and characterized. Study of these disorders has established the principle of how a mutant genotype can alter the function of the encoded protein, which in turn can lead to a distinct clinical phenotype. Genotype/phenotype correlations have provided important understanding of pathophysiological mechanisms of disease. Before presenting a brief overview of these disorders, we provide a summary of the structure and function of hemoglobin, along with the mechanism of assembly of its subunits, as background for the rationale and basis of the different categories of disorders in the classification. PMID:23378597

  2. A rare hemoglobin variant, Hb Belliard

    PubMed Central

    Benavides, Raul

    2017-01-01

    There are many documented variants of hemoglobin; however, other than a limited number (such as sickle cell disease), very few are known to have any clinical significance. As advances in detection and identification continue through gel electrophoresis, capillary electrophoresis, and DNA sequencing, more rare variants are identified. Without case reporting, the significance of these variants will remain unknown or continue to be thought of as insignificant. Here we report a rare hemoglobin variant, Hb Belliard, which was detected in a 68-year-old Indian immigrant to the United States. He presented with elevated hemoglobin and was found to have a unique peak on capillary electrophoresis. The specimen was sent for sequencing and was subsequently found to have Hb Belliard. Currently, Hb Belliard is thought to be insignificant.

  3. Xanthochromia of the skull bone associated with HbA1c.

    PubMed

    Schäfer, T; Klintschar, M; Lichtinghagen, R; Plagemann, I; Smith, A; Budde, E; Hagemeier, L

    2016-03-01

    The color of the surface of 105 skull bones (part of the parietal bone) was determined using a portable spectral colorimeter (spectro color(®)). By this means it was possible to characterize the color objectively according to the L*a*b* color system defined by the "International Commission de l'Eclairage" (CIE). Biochemical markers of carbohydrate metabolism, HbA1c from venous blood, and glucose/lactate concentrations from vitreous humor, were also determined, for assessment of the ante-mortem plasma glucose concentration using Traub's sum formula. As biochemical markers for lipid metabolism disorder, cholesterol, triglycerides, high density lipoprotein (HDL), low density lipoprotein (LDL) and very low density lipoprotein (VLDL) were all determined from venous blood. There is a significant correlation of bone yellowing with HbA1c (p<0.001) and age (p<0.001). The literature asserts a significant correlation between diabetic condition and yellowing of the skull bone. Despite efforts to find the substance responsible for the yellowing of the bone in chronic metabolism disorder, no significant correlation was found between bone color and lipoproteins/bone extracted lipid acids.

  4. Carnivora: primary structure of the hemoglobins from ratel (Mellivora capensis).

    PubMed

    Rodewald, K; Braunitzer, G; Göltenboth, R

    1988-10-01

    The erythrocytes of adult ratel contain two hemoglobin components, with two alpha- and one beta-chains. In this paper, their complete amino acid sequences are presented. The two alpha-chains differ in one residue at position 34 (Ala----Val) only. The primary structure of the chains was determined by sequencing the N-terminal regions (45 steps) and the tryptic peptides after their isolation from the digests by reversed-phase high-performance liquid chromatography. The alignment of these peptides was deduced from homology with other carnivora globins. The alpha-chains show 21 and the beta-chains 11 exchanges compared with human globin chains. In the alpha-chains, one heme- and two alpha 1/beta 1 contacts are exchanged. In the beta-chains there are three exchanges which involve one alpha 1/beta 1-, one alpha 1/beta 2- and one heme-contact. Between the ratel hemoglobin and those of carnivora a high degree of homology was found.

  5. [Contributions and prospects of hemoglobin derivatives].

    PubMed

    Remy, B; Deby-Dupont, G; Lamy, M

    1997-06-21

    Anoxia-reoxygenation leads to severe metabolic alterations, which result in a generalized inflammatory reaction and multiple organ dysfunction. Direct blood transfusion limits these alterations, but is accompanied by risk of transmission of infections or viral diseases. To avoid these risks, "blood substitutes" have been designed. The modified hemoglobins are not true blood substitutes because they do not possess the complex functions of erythrocytes. They are only oxygen carriers, with a short intravascular life, adapted for temporary use. They are stable, devoid of toxicity and antigenicity, and are able to carry and deliver O2 without regulation of this oxygen transport and without chemical reaction with O2. They possess rheologic properties and an oncotic pressure like those of blood. The use of natural hemoglobin solutions, obtained after lysis of erythrocytes, remains "at risk" because these solutions easily form methemoglobin, increase the oncotic pressure, present renal toxicity, and possess a too high affinity for O2. For these reasons, 5 types of modified hemoglobin solutions have been designed, prepared from human or bovine hemoglobin or by genetic engineering. These hemoglobins are highly purified to eliminate trace amounts of stroma, lipids and endotoxins, which are responsible for acute toxicity. They are modified by internal cross-linking between the monomers, or by binding to macromolecules. Afterwards, they can be polymerized or encapsulated in liposomes. The purpose of these modifications is to modulate the affinity for O2 (by decreasing the binding of O2 and increasing its delivery to tissue), to reduce the dissociation into monomers and to guard against oxidation into methemoglobin. Encapsulation in liposomes allows co-encapsulation of effector molecules and protective substances. Genetic engineering allows the production of recombinant hemoglobin with selective modifications. The modified hemoglobin solutions are essentially used in hemorrhagic

  6. The impact of the HbA1c level of type 2 diabetics on the structure of haemoglobin

    PubMed Central

    Ye, Shaoying; Ruan, Ping; Yong, Junguang; Shen, Hongtao; Liao, Zhihong; Dong, Xiaolei

    2016-01-01

    This study explores the impact of HbA1c levels on the structure of haemoglobin (Hb) in patients with type 2 diabetes. Seventy-four diabetic patients were classified into the following two groups based on their level of HbA1c: group A, patients with good glycaemic control (HbA1c < 7.0%, n = 36); group B, patients with persistent hyperglycaemia (HbA1c ≥ 9.0%, n = 38). Thirty-four healthy people served as controls (group H). Hb structure was examined by Fourier transform infrared spectroscopy (FTIR), and diabetic erythrocytes were modelled to estimate the impact of glucose on these cells and Hb. Increasing glucose concentrations altered both erythrocyte parameters and the Hb secondary structure. Group B differed significantly from group H (p < 0.05): in the former, the ordered Hb secondary structure had a strong tendency to transform into a disordered secondary structure, decreasing structural stability. We presumed here that high HbA1c levels might be a factor contributing to Hb structural modifications in diabetic patients. FTIR spectral analysis can provide a novel way to investigate the pathogenesis of type 2 diabetes mellitus. PMID:27624402

  7. Hemoglobin D-Punjab: origin, distribution and laboratory diagnosis

    PubMed Central

    Torres, Lidiane de Souza; Okumura, Jéssika Viviani; Silva, Danilo Grünig Humberto da; Bonini-Domingos, Claudia Regina

    2015-01-01

    This review discusses hemoglobin D-Punjab, also known as hemoglobin D-Los Angeles, one of the most common hemoglobin variants worldwide. It is derived from a point mutation in the beta-globin gene (HBB: c.364G>C; rs33946267) prevalent in the Punjab region, Northwestern Indian. Hemoglobin D-Punjab can be inherited in heterozygosis with hemoglobin A causing no clinical or hematological alterations, or in homozygosis, the rarest form of inheritance, a condition that is commonly not related to clinical symptomatology. Moreover, this variant can exist in association with other hemoglobinopathies, such as thalassemias; the most noticeable clinical alterations occur when hemoglobin D-Punjab is associated to hemoglobin S. The clinical manifestations of this association can be similar to homozygosis for hemoglobin S. Although hemoglobin D-Punjab is a common variant globally with clinical importance especially in cases of double heterozygosis, hemoglobin S/D-Punjab is still understudied. In Brazil, for example, hemoglobin D-Punjab is the third most common hemoglobin variant. Thus, this paper summarizes information about the origin, geographic distribution, characterization and occurrence of hemoglobin D-Punjab haplotypes to try to improve our knowledge of this variant. Moreover, a list of the main techniques used in its identification is provided emphasizing the importance of complementary molecular analysis for accurate diagnosis. PMID:25818823

  8. Haptoglobin attenuates hemoglobin-induced heme oxygenase-1 in renal proximal tubule cells and kidneys of a mouse model of sickle cell disease.

    PubMed

    Chintagari, Narendranath Reddy; Nguyen, Julia; Belcher, John D; Vercellotti, Gregory M; Alayash, Abdu I

    2015-03-01

    Sickle cell disease (SCD), a hereditary hemolytic disorder is characterized by chronic hemolysis, oxidative stress, vaso-occlusion and end-organ damage. Hemolysis releases toxic cell-free hemoglobin (Hb) into circulation. Under physiologic conditions, plasma Hb binds to haptoglobin (Hp) and forms Hb-Hp dimers. The dimers bind to CD163 receptors on macrophages for further internalization and degradation. However, in SCD patients plasma Hp is depleted and free Hb is cleared primarily by proximal tubules of kidneys. Excess free Hb in plasma predisposes patients to renal damage. We hypothesized that administration of exogenous Hp reduces Hb-mediated renal damage. To test this hypothesis, human renal proximal tubular cells (HK-2) were exposed to HbA (50μM heme) for 24h. HbA increased the expression of heme oxygenase-1 (HO-1), an enzyme which degrades heme, reduces heme-mediated oxidative toxicity, and confers cytoprotection. Similarly, infusion of HbA (32μM heme/kg) induced HO-1 expression in kidneys of SCD mice. Immunohistochemistry confirmed the increased HO-1 expression in the proximal tubules of the kidney. Exogenous Hp attenuated the HbA-induced HO-1 expression in vitro and in SCD mice. Our results suggest that Hb-mediated oxidative toxicity may contribute to renal damage in SCD and that Hp treatment reduces heme/iron toxicity in the kidneys following hemolysis.

  9. Hemoglobin isoform differentiation and allosteric regulation of oxygen binding in the turtle, Trachemys scripta

    PubMed Central

    Damsgaard, Christian; Storz, Jay F.; Hoffmann, Federico G.

    2013-01-01

    When freshwater turtles acclimatize to winter hibernation, there is a gradual transition from aerobic to anaerobic metabolism, which may require adjustments of blood O2 transport before turtles become anoxic. Here, we report the effects of protons, anionic cofactors, and temperature on the O2-binding properties of isolated hemoglobin (Hb) isoforms, HbA and HbD, in the turtle Trachemys scripta. We determined the primary structures of the constituent subunits of the two Hb isoforms, and we related the measured functional properties to differences in O2 affinity between untreated hemolysates from turtles that were acclimated to normoxia and anoxia. Our data show that HbD has a consistently higher O2 affinity compared with HbA, whereas Bohr and temperature effects, as well as thiol reactivity, are similar. Although sequence data show amino acid substitutions at two known β-chain ATP-binding site positions, we find high ATP affinities for both Hb isoforms, suggesting an alternative and stronger binding site for ATP. The high ATP affinities indicate that, although ATP levels decrease in red blood cells of turtles acclimating to anoxia, the O2 affinity would remain largely unchanged, as confirmed by O2-binding measurements of untreated hemolysates from normoxic and anoxic turtles. Thus, the increase in blood-O2 affinity that accompanies winter acclimation is mainly attributable to a decrease in temperature rather than in concentrations of organic phosphates. This is the first extensive study on freshwater turtle Hb isoforms, providing molecular evidence for adaptive changes in O2 transport associated with acclimation to severe hypoxia. PMID:23986362

  10. Hemoglobin analyses in the Netherlands reveal more than 80 different variants including six novel ones.

    PubMed

    van Zwieten, Rob; Veldthuis, Martijn; Delzenne, Barend; Berghuis, Jeffrey; Groen, Joke; Ait Ichou, Fatima; Clifford, Els; Harteveld, Cornelis L; Stroobants, An K

    2014-01-01

    More than 20,000 blood samples of individuals living in The Netherlands and suspected of hemolytic anemia or diabetes were analyzed by high resolution cation exchange high performance liquid chromatography (HPLC). Besides common disease-related hemoglobins (Hbs), rare variants were also detected. The variant Hbs were retrospectively analyzed by capillary zone electrophoresis (CZE) and by isoelectric focusing (IEF). For unambiguous identification, the globin genes were sequenced. Most of the 80 Hb variants detected by initial screening on HPLC were also separated by capillary electrophoresis (CE), but a few variants were only detectable with one of these methods. Some variants were unstable, had thalassemic properties or increased oxygen affinity, and some interfered with Hb A2 measurement, detection of sickle cell Hb or Hb A1c quantification. Two of the six novel variants, Hb Enschede (HBA2: c.308G  > A, p.Ser103Asn) and Hb Weesp (HBA1: c.301C > T, p.Leu101Phe), had no clinical consequences. In contrast, two others appeared clinically significant: Hb Ede (HBB: c.53A > T, p.Lys18Met) caused thalassemia and Hb Waterland (HBB: c.428C > T, pAla143Val) was related to mild polycytemia. Hb A2-Venlo (HBD: c.193G > A, p.Gly65Ser) and Hb A2-Rotterdam (HBD: c.38A > C, p.Asn13Thr) interfered with Hb A2 quantification. This survey shows that HPLC analysis followed by globin gene sequencing of rare variants is an effective method to reveal Hb variants.

  11. Hemoglobin: A Nitric-Oxide Dioxygenase

    PubMed Central

    Gardner, Paul R.

    2012-01-01

    Members of the hemoglobin superfamily efficiently catalyze nitric-oxide dioxygenation, and when paired with native electron donors, function as NO dioxygenases (NODs). Indeed, the NOD function has emerged as a more common and ancient function than the well-known role in O2 transport-storage. Novel hemoglobins possessing a NOD function continue to be discovered in diverse life forms. Unique hemoglobin structures evolved, in part, for catalysis with different electron donors. The mechanism of NOD catalysis by representative single domain hemoglobins and multidomain flavohemoglobin occurs through a multistep mechanism involving O2 migration to the heme pocket, O2 binding-reduction, NO migration, radical-radical coupling, O-atom rearrangement, nitrate release, and heme iron re-reduction. Unraveling the physiological functions of multiple NODs with varying expression in organisms and the complexity of NO as both a poison and signaling molecule remain grand challenges for the NO field. NOD knockout organisms and cells expressing recombinant NODs are helping to advance our understanding of NO actions in microbial infection, plant senescence, cancer, mitochondrial function, iron metabolism, and tissue O2 homeostasis. NOD inhibitors are being pursued for therapeutic applications as antibiotics and antitumor agents. Transgenic NOD-expressing plants, fish, algae, and microbes are being developed for agriculture, aquaculture, and industry. PMID:24278729

  12. Comparative immunology of Galapagos iguana hemoglobins.

    PubMed

    Higgins, P J; Rand, C S

    1975-09-01

    The antigenic properties of the major hemoglobin component of the Galapgaos iguanas were studied using second-approximation qualitative and quantitative immunochemical techniques. Phylogenetic distances, relative to the Galapagos marine iguana. Amblyrhynchus cristatus, were established on the basis of immunological cross-reactions.

  13. Unrecognized hemoglobin SE disease as microcytosis

    PubMed Central

    Cooper, Barry; Guileyardo, Joseph; Mora, Adan

    2016-01-01

    Hemoglobin SE disease was first described during the 1950s as a relatively benign microcytosis, but increasing prevalence has revealed a predisposition towards vasoocclusive sickling. Recognition of SE hemoglobinopathies’ potential complications is crucial so medical measures can be utilized to avoid multiorgan injury. PMID:27365881

  14. RGB mapping of hemoglobin distribution in skin

    NASA Astrophysics Data System (ADS)

    Jakovels, Dainis; Spigulis, Janis; Rogule, Laura

    2011-07-01

    An experimental RGB imaging system based on commercial color camera was constructed, and its potential for mapping of hemoglobin distribution in skin was studied. Two types of LEDs (RGB and white "warm" LEDs) were compared as illuminators for acquiring images of vascular and pigmented skin malformations. A novel approach for studies of skin capillary refill by RGB analysis has been proposed and discussed.

  15. Hemoglobin-mediated nitric oxide signaling

    PubMed Central

    Helms, Christine; Kim-Shapiro, Daniel B.

    2013-01-01

    The rate that hemoglobin reacts with nitric oxide (NO) is limited by how fast NO can diffuse into the heme pocket. The reaction is as fast as any ligand/protein reaction can be and the result, when hemoglobin is in its oxygenated form, is formation of nitrate in what is known as the dioxygenation reaction. As nitrate, at the concentrations made through the dioxygenation reaction, is biologically inert, the only role hemoglobin was once thought to play in NO signaling was to inhibit it. However, there are now several mechanisms that have been discovered by which hemoglobin may preserve, control, and even create NO activity. These mechanisms involve compartmentalization of reacting species and conversion of NO from or into other species such as nitrosothiols or nitrite which could transport NO activity. Despite the tremendous amount of work devoted to this field, major questions concerning precise mechanisms of NO activity preservation as well as if and how Hb creates NO activity remain unanswered. PMID:23624304

  16. Metastable Polymerization of Sickle Hemoglobin in Droplets

    PubMed Central

    Aprelev, Alexey; Weng, Weijun; Zakharov, Mikhail; Rotter, Maria; Yosmanovich, Donna; Kwong, Suzanna; Briehl, Robin W.; Ferrone, Frank A.

    2007-01-01

    Sickle cell disease arises from a genetic mutation of one amino acid in each of the two hemoglobin β chains, leading to the polymerization of hemoglobin in the red cell upon deoxygenation, and is characterized by vascular crises and tissue damage due to the obstruction of small vessels by sickled cells. It has been an untested assumption that, in red cells that sickle, the growing polymer mass would consume monomers until the thermodynamically well-described monomer solubility was reached. By photolyzing droplets of sickle hemoglobin suspended in oil we find that polymerization does not exhaust the available store of monomers, but stops prematurely, leaving the solutions in a supersaturated, metastable state typically 20% above solubility at 37°C, though the particular values depend on the details of the experiment. We propose that polymer growth stops because the growing ends reach the droplet edge, whereas new polymer formation is thwarted by long nucleation times, since the hemoglobin concentration is lowered by depletion of monomers into the polymers that have formed. This finding suggests a new aspect to the pathophysiology of sickle cell disease, namely, that cells deoxygenated in the microcirculation are not merely undeformable, but will actively wedge themselves tightly against the walls of the microvasculature by a ratchet-like mechanism driven by the supersaturated solution. PMID:17493634

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

    PubMed

    Wisedpanichkij, Raewadee; Jindadamrongwech, Sumalee; Butthep, Punnee

    2015-01-01

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

  18. Hemoglobin Hasharon (α247 his(CD5)β2): a hemoglobin found in low concentration

    PubMed Central

    Charache, S.; Mondzac, A. M.; Gessner, U.

    1969-01-01

    Hemoglobin Hasharon (α247 his(CD5)β2) was found to comprise only 16-19% of hemolysates of carriers. These heterozygotes appeared to have mild, compensated, hemolytic anemia. Hb Hasharon was more heat-labile than hemoglobins A, S, or C. Its specific activity was higher than that of Hb A after administration of 59Fe to two carriers. When hemoglobin synthesis by bone marrow cells was studied in vitro, about 18% of incorporated leucine appeared in the Hb Hasharon fraction. It is suggested that Hb Hasharon is unstable in vivo, and that mild hemolytic anemia and a relatively small decrease in its concentration in hemolysates result from its denaturation within red cells. Decreased synthesis, which appears to be the major cause of the small amount of abnormal hemoglobin, may protect heterozygotes from clinically significant hemolytic anemia. Images PMID:5780195

  19. Analysis of bicarbonate binding to crocodilian hemoglobin.

    PubMed

    Bauer, C; Forster, M; Gros, G; Mosca, A; Perrella, M; Rollema, H S; Vogel, D

    1981-08-25

    Crocodilian hemoglobin has a high intrinsic oxygen affinity but does not react with those organic phosphate esters that normally control the oxygen affinity of blood in higher vertebrates. Instead, its oxygen affinity is greatly lowered by CO2. The present study was undertaken to determine the nature of the CO2 binding to the hemoglobin of a crocodilian species, the Caiman, both qualitatively and quantitatively. The following parameters were measured: (a) carbamino compounds of deoxy- and oxyhemoglobin, (b) the effect of CO2 (at constant pH) on the oxygen affinity of Caiman hemoglobin, (c) total CO2 concentration of hemoglobin solutions at different pH and pCO2 values, and (d) the effect of CO2 on CD spectra of Caiman aquomethemoglobin. An analysis of the results of these measurements revealed that CO2 binding in the form of carbamate was not oxygen-linked and cannot, therefore, mediate the CO2 effect on the oxygen affinity. It was found, however, that 2 mol of bicarbonate can be bound/hemoglobin tetramer and that the association constant of the bicarbonate anion greatly depends upon the state of ligation. At pH 7.02 and 25 degrees C, a numerical value of 2.0 X 10(3) M-1 was obtained for deoxyhemoglobin, while for oxyhemoglobin no significant bicarbonate binding could be observed. At more alkaline pH (pH greater than or equal to 7.5), the association constant for deoxyhemoglobin decreases. Circular dichroism of Caiman aquomethemoglobin decreased considerably in the 287-nm region upon addition of CO2 at constant pH, an effect very similar to the one caused by inositol hexaphosphate in human aquomethemoglobin.

  20. Validation and Modification of Dried Blood Spot-Based Glycosylated Hemoglobin Assay for the Longitudinal Aging Study in India

    PubMed Central

    Hu, Peifeng; Edenfield, Michael; Potter, Alan; Kale, Varsha; Risbud, Arun; Williams, Sharon; Lee, Jinkook; Bloom, David E.; Crimmins, Eileen; Seeman, Teresa

    2014-01-01

    Objectives This study aims to validate a modified dried blood spot (DBS)-based glycosylated hemoglobin (HbA1c) assay protocol, after a pretest in India showed poor correlation between the original DBS-based protocol and venous results. Methods The original protocol was tested on different chemistry analyzers and then simplified at the University of Washington (UW). A second pretest was conducted in India to validate the modified assay protocol, using 44 quality control specimens. Results Data from UW indicated that, using the original protocol, the correlation coefficients between DBS and venous results were above 0.98 on both Bio-Rad and Olympus chemistry analyzers. The protocol worked equally well on filter paper, with or without pre-treatment, and when the recommended amount of blood spot material, or less, was used. A second pretest of the modified protocol confirmed that DBS-based levels from both Olympus and Roche chemistry analyzers were well correlated with DBS results from UW (correlation coefficients were above 0.96), as well as with venous values (correlation coefficients were above 0.94). Conclusions The DBS-based HbA1c values are highly correlated with venous results. The pre-treatment of filter paper does not appear to be necessary. The poor results from the first pretest are probably due to factors unrelated to the protocol, such as problems with the chemistry analyzer or assay reagents. PMID:25472916

  1. Using both Principal Component Analysis and Reduced Rank Regression to Study Dietary Patterns and Diabetes in Chinese Adults

    PubMed Central

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

    2014-01-01

    Objective We examined the association between dietary patterns and diabetes using the strengths of two methods: principal component analysis (PCA) to identify the eating patterns of the population and reduced rank regression (RRR) to derive a pattern that explains the variation in hemoglobin A1c (HbA1c), homeostasis model of insulin resistance (HOMA-IR), and fasting glucose. Design We measured diet over a 3-day period with 24-hour recalls and a household food inventory in 2006 and used it to derive PCA and RRR dietary patterns. The outcomes were measured in 2009. Setting Adults (n = 4,316) from the China Health and Nutrition Survey. Results The adjusted odds ratio for diabetes prevalence (HbA1c ≥ 6.5%), comparing the highest dietary pattern score quartile to the lowest, was 1.26 (0.76, 2.08) for a modern high-wheat pattern (PCA; wheat products, fruits, eggs, milk, instant noodles and frozen dumplings), 0.76 (0.49, 1.17) for a traditional southern pattern (PCA; rice, meat, poultry, and fish), and 2.37 (1.56, 3.60) for the pattern derived with RRR. By comparing the dietary pattern structures of RRR and PCA, we found that the RRR pattern was also behaviorally meaningful. It combined the deleterious effects of the modern high-wheat (high intake of wheat buns and breads, deep-fried wheat, and soy milk) with the deleterious effects of consuming the opposite of the traditional southern (low intake of rice, poultry and game, fish and seafood). Conclusions Our findings suggest that using both PCA and RRR provided useful insights when studying the association of dietary patterns with diabetes. PMID:26784586

  2. 21 CFR 864.7455 - Fetal hemoglobin assay.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Fetal hemoglobin assay. 864.7455 Section 864.7455 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... hemoglobin polypeptide chains). The hemoglobin determination may be made by methods such as...

  3. 21 CFR 864.7455 - Fetal hemoglobin assay.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Fetal hemoglobin assay. 864.7455 Section 864.7455 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... hemoglobin polypeptide chains). The hemoglobin determination may be made by methods such as...

  4. 21 CFR 864.7455 - Fetal hemoglobin assay.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Fetal hemoglobin assay. 864.7455 Section 864.7455 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... hemoglobin polypeptide chains). The hemoglobin determination may be made by methods such as...

  5. 21 CFR 864.7455 - Fetal hemoglobin assay.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Fetal hemoglobin assay. 864.7455 Section 864.7455 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... hemoglobin polypeptide chains). The hemoglobin determination may be made by methods such as...

  6. Sensitivity of Routine Tests for Urine Protein to Hemoglobin

    PubMed Central

    Jansen, Barbara S.; Lumsden, John H.

    1985-01-01

    Increasing concentrations of canine hemoglobin were added to aliquots of urine and saline to determine the relative sensitivity of several hemoglobin and protein detection methods including commercial reagent strips and sulfosalicylic acid. The hemoglobin detection pads of the reagent strips were 50 times more sensitive than the protein detection pads, indicating the presence of hemoglobin at a concentration of 0.001 g/L whereas the protein pads did not react positively unless the hemoglobin concentration exceeded 0.05 g/L. The sulfosalicylic acid test was the least sensitive, detecting hemoglobin only at concentrations of 0.4 g/L or higher. These results were similar for hemoglobin added either in the form of lysed red blood cells, intact red blood cells or associated with plasma proteins in whole blood. It was shown that a urine hemoglobin concentration eliciting less than the maximal score on the hemoglobin detection pad will not be detected as “protein” either with the commercial urinalysis strips or with sulfosalicylic acid. It was also seen that hemoglobin becomes visible as a red pigment when exceeding 0.3-0.5 g/L in a clear, light urine. It follows that a positive urine protein reading in the presence of a positive but less than maximal hemoglobin score or a protein reading exceeding 1.0 g/L in a nonpigmented urine indicates “true” proteinuria in excess of hemoglobin and plasma proteins associated with urinary tract hemorrhage. PMID:17422554

  7. Photopyroelectric Technique for Hemoglobin Assessment in Human Blood

    NASA Astrophysics Data System (ADS)

    Balderas-López, J. A.; Gómez y Gómez, Y. M.; Bautista-Ramírez, M. E.

    2015-06-01

    A new photopyroelectric (PPE) methodology, for optical characterization of general liquids, was used for the assessment of hemoglobin in human blood. The optical absorption coefficient of a hemoglobin reference was measured with this PPE methodology and its corresponding absorptivity, at 532 nm, was obtained. This last reference was used for hemoglobin quantification of blood from a healthy man.

  8. 21 CFR 522.1125 - Hemoglobin glutamer-200 (bovine).

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Hemoglobin glutamer-200 (bovine). 522.1125 Section... § 522.1125 Hemoglobin glutamer-200 (bovine). (a) Specifications. Each 125 milliliter bag contains 13 grams per deciliter of polymerized hemoglobin of bovine origin in modified Lactated Ringer's...

  9. 21 CFR 522.1125 - Hemoglobin glutamer-200 (bovine).

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Hemoglobin glutamer-200 (bovine). 522.1125 Section... § 522.1125 Hemoglobin glutamer-200 (bovine). (a) Specifications. Each 125 milliliter bag contains 13 grams per deciliter of polymerized hemoglobin of bovine origin in modified Lactated Ringer's...

  10. 21 CFR 522.1125 - Hemoglobin glutamer-200 (bovine).

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Hemoglobin glutamer-200 (bovine). 522.1125 Section... § 522.1125 Hemoglobin glutamer-200 (bovine). (a) Specifications. Each 125 milliliter bag contains 13 grams per deciliter of polymerized hemoglobin of bovine origin in modified Lactated Ringer's...

  11. 21 CFR 864.7455 - Fetal hemoglobin assay.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Fetal hemoglobin assay. 864.7455 Section 864.7455...) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Kits and Packages § 864.7455 Fetal hemoglobin assay. (a) Identification. A fetal hemoglobin assay is a device that is used to determine the...

  12. 21 CFR 522.1125 - Hemoglobin glutamer-200 (bovine).

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Hemoglobin glutamer-200 (bovine). 522.1125 Section... § 522.1125 Hemoglobin glutamer-200 (bovine). (a) Specifications. Each 125 milliliter bag contains 13 grams per deciliter of polymerized hemoglobin of bovine origin in modified Lactated Ringer's...

  13. Bioimaging techniques for subcellular localization of plant hemoglobins and measurement of hemoglobin-dependent nitric oxide scavenging in planta.

    PubMed

    Hebelstrup, Kim H; Østergaard-Jensen, Erik; Hill, Robert D

    2008-01-01

    Plant hemoglobins are ubiquitous in all plant families. They are expressed at low levels in specific tissues. Several studies have established that plant hemoglobins are scavengers of nitric oxide (NO) and that varying the endogenous level of hemoglobin in plant cells negatively modulates bioactivity of NO generated under hypoxic conditions or during cellular signaling. Earlier methods for determination of hemoglobin-dependent scavenging in planta were based on measuring activity in whole plants or organs. Plant hemoglobins do not contain specific organelle localization signals; however, earlier reports on plant hemoglobin have demonstrated either cytosolic or nuclear localization, depending on the method or cell type investigated. We have developed two bioimaging techniques: one for visualization of hemoglobin-catalyzed scavenging of NO in specific cells and another for visualization of subcellular localization of green fluorescent protein-tagged plant hemoglobins in transformed Arabidopsis thaliana plants.

  14. The relationship between periapical lesions and the serum levels of glycosylated hemoglobin and C-reactive protein in type 2 diabetic patients

    PubMed Central

    Al-Zahrani, Mohammad S.; Abozor, Basel M.; Zawawi, Khalid H.

    2017-01-01

    Objectives: To investigate the relationship between the presence of periapical lesions (PL) and levels of glycosylated hemoglobin (HbA1c), and C-reactive protein (CRP) in patients with type 2 diabetes. Methods: This cross-sectional study was conducted at Ibn Sina National College for Medical Studies, Jeddah, Kingdom of Saudi Arabia, between September 2013 and February 2015. Medical and dental history and Sociodemographic data were obtained from participants. Dental and periodontal examinations were conducted and blood samples were obtained to determine levels of HbA1c and CRP. The presence of PL was recorded from panoramic and periapical radiographs. Descriptive statistics and multivariable linear and logistic regression models were used for data analyses. Results: One hundred patients were included; mean age was 48.9 ± 8.5 years. Of these patients, 14% had no PL, whereas 25% had one or 2 lesions, 32% had 3 or 4 lesions, and 29% had ≥5 PL. The mean HbA1c was 9.8% (± 2.5) mg/L and CRP was 6.9 mg/L (± 6.3). The presence of PL was significantly associated with a higher level of HbA1c independent of age, gender, probing depth, and plaque index (p=0.023). Individuals with PL were also more likely to have a high CRP level (>3 mg/L) independent of the previous covariates (odds ratio: 1.19; 95% confidence interval: 1.01-1.41). Conclusion: Periapical lesions are associated with a poorer glycemic control and a higher CRP level in type 2 diabetic patients. PMID:28042628

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

    PubMed

    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.

  16. Distribution of Glycated Haemoglobin According to Early-Life and Contemporary Characteristics in Adolescents and Adults without Diabetes: The 1982 and 1993 Pelotas Birth Cohorts

    PubMed Central

    Restrepo-Méndez, María Clara; Silveira, Vera M.; Miranda, Jaime J.; Gonçalves, Helen D.; Oliveira, Isabel O.; Horta, Bernardo L.; Gigante, Denise P.; Menezes, Ana Maria; Assunção, Maria Cecília F.

    2016-01-01

    Aim Glycated haemoglobin (HbA1c), a marker of glucose control in individuals with diabetes mellitus, is also related with the incidence of cardiometabolic risk in populations free of disease. The aim of this study was to describe the distribution of HbA1c levels according to early-life and contemporary factors in adolescents and adults without diabetes mellitus. Methods HbA1c was measured in adults aged 30 years and adolescents aged 18 years who are participants in the 1982 and 1993 Pelotas Birth Cohorts, respectively. Bivariate and multivariate analyses were performed to describe the HbA1c mean values according to early-life and contemporary characteristics collected prospectively since birth. Results The distribution of the HbA1c was approximately normal in both cohorts, with a mean (SD) 5.10% (0.43) in the 1982 cohort, and 4.89% (0.50) in the 1993 cohort. HbA1c mean levels were significantly higher in individuals self-reported as black/brown skin color compared to those self-reported as white in both cohorts. Parental history of diabetes was associated with higher HbA1c mean in adults, while stunting at one year old presented an inverse relation with the outcome in adolescents. No other early and contemporary factors were associated with HbA1c levels in adults or adolescents. Conclusions We found a consistent relationship between HbA1c and skin color in both cohorts. Further research is needed to understand the role of genomic ancestry on levels of HbA1c concentrations which may inform policies and preventive actions for diabetes mellitus and cardiometabolic risk. PMID:27626274

  17. Hemoglobin-Based Nanoarchitectonic Assemblies as Oxygen Carriers.

    PubMed

    Jia, Yi; Duan, Li; Li, Junbai

    2016-02-10

    Safe and effective artificial oxygen carriers are the subject of great interest due to the problems of traditional blood transfusion and enormous demand in clinical use. In view of its unique oxygen-transport ability and normal metabolic pathways, hemoglobin is regarded as an ideal oxygen-carrying unit. With advances in nano-biotechnology, hemoglobin assemblies as artificial oxygen carriers achieve great development. Here, recent progress on hemoglobin-based oxygen carriers is highlighted in view of two aspects: acellular hemoglobin-based oxygen carriers and cellular hemoglobin-based oxygen carriers. These novel oxygen carriers exhibit advantages over traditional carriers and will greatly promote research on reliable and feasible oxygen carriers.

  18. The Change in HbA1c Associated with Initial Adherence and Subsequent Change in Adherence among Diabetes Patients Newly Initiating Metformin Therapy.

    PubMed

    Nichols, Gregory A; Rosales, A Gabriela; Kimes, Teresa M; Tunceli, Kaan; Kurtyka, Karen; Mavros, Panagiotis

    2016-01-01

    Introduction. Whether changes in adherence are associated with changes in HbA1c is assumed but not known. Methods. We conducted a observational study of 2,844 type 2 diabetes patients who initiated metformin as their first antihyperglycemic drug. Using HbA1c measures before, 6-12 months after, and up to 3 years after metformin initiation, we analyzed HbA1c change as a function of initial adherence and change in adherence. Results. Compared with no adherence, initial adherence of 50-79% was associated with an adjusted reduction in HbA1c of 0.45% while adherence ≥80% was associated with HbA1c reduction of 0.73%. Change from some initial adherence (1-79%) to total nonadherence was associated with 0.25% increase in HbA1c. Change from some to full adherence was associated with an HbA1c decrease of 0.15%. Those associations were accentuated among patients not in glycemic control: change from some to no adherence was associated with an HbA1c increase of 0.63% and change from some to full adherence was associated with an HbA1c decrease of 0.40%. Conclusions. Initial adherence to newly prescribed metformin therapy produces substantial HbA1c reduction. Among those with modest adherence but suboptimal glycemic control, the difference between moving to full adherence versus nonadherence results in lower HbA1c of one percentage point.

  19. Light Scattering and Absorption Studies of Sickle Cell Hemoglobin

    NASA Astrophysics Data System (ADS)

    Kim-Shapiro, Daniel

    1997-11-01

    The use of physical techniques has been very important in understanding the pathophysiology of sickle cell disease. In particular, light scattering and absorption studies have been used to measure the kinetics of sickle cell hemoglobin polymerization and depolymerization (melting). The theory of sickle cell polymerization that has been derived and tested by these methods has not only led to an increased understanding of the pathophysiology of the disease but has also led to improved treatment strategies. Sickle cell disease effects about 1 out of 600 people of African descent born in the United States. The disease is caused by a mutant form of hemoglobin (the oxygen transporting molecule in the blood), hemoglobin S (HbS), which differs from normal adult hemoglobin by the substitution of a single amino acid for another. The polymerization of HbS, which occurs under conditions of low oxygen pressure, causes distortion and increased rigidity of the sickle red blood cell that leads to blockage of the capillaries and a host of resulting complications. The disease is associated with tissue damage, severe painful crises and a high degree of mortality. Light scattering studies of purified HbS and whole cells (conducted by F.A. Ferrone, J. Hofrichter, W.A. Eaton, and their associates) have been used to determine the mechanism of HbS polymerization. Polymerization will generally not occur when the hemoglobin is in an oxygen-rich environment. The question is, when HbS is rapidly deoxygenated (as it is when going from the lungs to the tissues) what is the kinetics of polymerization? Photolysis methods were used to rapidly deoxygenate HbS and light scattering was used as a function of time to measure the kinetics of polymerization. Polarized light scattering may be a more effective way to measure polymer content than total intensity light scattering. It was found that no polymerization occurs during a period of time called the delay time and subsequent polymerization occurs

  20. [Abnormal hemoglobins in Negroid Ecuadorian populations].

    PubMed

    Jara, N O; Guevara Espinoza, A; Guderian, R H

    1989-02-01

    The prevalence of hemoglobinopathies was determined in the black race located in two distinct geographical areas in Ecuador; in the coastal province of Esmeraldas, particularly the Santiago basin (Rio Cayapas and Rio Onzoles) and in the province of Imbabura, particularly in the intermoutain valley, Valle de Chota. A total of 2038 blood samples were analyzed, 1734 in Esmeraldas and 304 in Inbabura, of which 23.2% (473 individuals) were found to be carriers of abnormal hemoglobins, 25.4% (441) in Esmeraldas and 10.5% (32) in Imbabura. The abnormal hemoglobins found in Esmeraldas were Hb AS (19.2%), Hb AC (5.0%), Hb SS (0.6%) and Hb SC (0.5%) while in Imbabura only Hb AS (9.5%) and Hb AC (0.9%) were found. The factors that could influence the difference in prevalence found in the two geographical areas are discussed.

  1. Haematological parameters and HbA2 levels in beta-thalassaemia trait with coincident iron deficiency.

    PubMed

    Madan, N; Sikka, M; Sharma, S; Rusia, U

    1998-07-01

    Iron status was estimated in 463 heterozygous beta-thalassaemics to delineate the effect of iron deficiency (ID) on the haematological parameters and expression of HbA2 in these patients. One hundred and twenty six (27.2%) traits had coincident ID. These iron deficient traits had a significantly (p < 0.0002), higher prevalence of anaemia (90.5%) as compared to iron replete traits (71.5%). Mean haemoglobin concentration was significantly lower (p < 0.0001) in beta-thalassaemics with ID (10.7 +/- 1.5) g/al as compared to those without ID (11.6 +/- 1.6 g/dl). Mean MCV and MCH were significantly lowered (p < 0.0001) in patients of beta-thalassaemia trait (BTT) with ID than in these without ID. Mean HbA2 was not significantly different in the two groups of traits and was elevated (> or = 3.5%) in all except one patient. However, mean HbA2/cell was significantly (p < 0.05) lower in traits with ID. The effect of ID in BTT was apparent with significant lowering of haemoglobin concentration and increased prevalence of anaemia. Iron therapy is warranted in iron deficient traits and would help in significantly raising their haemoglobin concentration. Elevation in HbA2 values was striking and could be used with reliability for diagnosis of BTT even in the presence of ID.

  2. Free heme and sickle hemoglobin polymerization

    NASA Astrophysics Data System (ADS)

    Uzunova, Veselina V.

    This work investigates further the mechanism of one of the most interesting of the protein self-assembly systems---the polymerization of sickle hemoglobin and the role of free heme in it. Polymerization of sickle hemoglobin is the primary event in the pathology of a chronic hemolytic condition called sickle cell anemia with complex pathogenesis, unexplained variability and symptomatic treatment. Auto-oxidation develops in hemoglobin solutions exposed to room temperature and causes release of ferriheme. The composition of such solutions is investigated by mass spectrometry. Heme dimers whose amount corresponds to the initial amounts of heme released from the protein are followed. Differences in the dimer peak height are established for hemoglobin variants A, S and C and depending on the exposure duration. The effects of free heme on polymerization kinetics are studied. Growth rates and two characteristic parameters of nucleation are measured for stored Hb S. After dialysis of polymerizing solutions, no spherulites are detected at moderately high supersaturation and prolonged exposure times. The addition of 0.16-0.26 mM amounts of heme to dialyzed solutions leads to restoration of polymerization. The measured kinetic parameters have higher values compared to the ones before dialysis. The amount of heme in non-dialyzed aged solution is characterized using spectrophotometry. Three methods are used: difference in absorbance of dialyzed and non-dialyzed solutions, characteristic absorbance of heme-albumin complex and absorbance of non-dialyzed solutions with added potassium cyanide. The various approaches suggest the presence of 0.12 to 0.18 mM of free ferriheme in such solutions. Open questions are whether the same amounts of free heme are present in vivo and whether the same mechanism operates intracellulary. If the answer to those questions is positive, then removal of free heme from erythrocytes can influence their readiness to sickle.

  3. Carboxyalkylated Hemoglobin as a Potential Blood Substitute.

    DTIC Science & Technology

    1987-01-24

    I- 1.8 MICROCOpy RESOLUTION TEST CHART NAT OWAI BURErAU Of STANDARDS 1963-A OliC FIE COPJ Alit D CARBOXYALKYLATED HEMOGLOBIN AS AN POTENTIAL BLOOD...valine derivatives as the monocarboxymethyl and dicarboxymethyl derivatives, respectively. These derivatives are ninhydrin -negative. The lysine...derivative, wLich was eluted in 1 M acetic acid, was applied to an amino acid analyzer since it is ninhydrin -positive. Its position coincided with that of

  4. Pomalidomide and lenalidomide regulate erythropoiesis and fetal hemoglobin production in human CD34+ cells.

    PubMed

    Moutouh-de Parseval, Laure A; Verhelle, Dominique; Glezer, Emilia; Jensen-Pergakes, Kristen; Ferguson, Gregory D; Corral, Laura G; Morris, Christopher L; Muller, George; Brady, Helen; Chan, Kyle

    2008-01-01

    Sickle-cell disease (SCD) and beta thalassemia constitute worldwide public health problems. New therapies, including hydroxyurea, have attempted to augment the synthesis of fetal hemoglobin (HbF) and improve current treatment. Lenalidomide and pomalidomide are members of a class of immunomodulators used as anticancer agents. Because clinical trials have demonstrated that lenalidomide reduces or eliminates the need for transfusions in some patients with disrupted blood cell production, we investigated the effects of lenalidomide and pomalidomide on erythropoiesis and hemoglobin synthesis. We used an in vitro erythropoiesis model derived from human CD34+ progenitor cells from normal and SCD donors. We found that both compounds slowed erythroid maturation, increased proliferation of immature erythroid cells, and regulated hemoglobin transcription, resulting in potent induction of HbF without the cytotoxicity associated with other HbF inducers. When combined with hydroxyurea, pomalidomide and, to a lesser extent, lenalidomide were found to have synergistic effects on HbF upregulation. Our results elucidate what we believe to be a new mechanism of action of pomalidomide and lenalidomide and support the hypothesis that pomalidomide, used alone or in combination with hydroxyurea, may improve erythropoiesis and increase the ratio of fetal to adult hemoglobin. These findings support the evaluation of pomalidomide as an innovative new therapy for beta-hemoglobinopathies.

  5. Role of Altered Venous Blood Lactate and HbA1c in Women with Gestational Diabetes Mellitus

    PubMed Central

    Santhosh, N U; Krishnamurthy, N; Chethan, Chethana; Shilpashree, M K

    2016-01-01

    Introduction Being a mirror image of metabolic syndrome, Gestational Diabetes Mellitus (GDM) is associated with significant maternal and fetal morbidity. Increased blood lactate concentration and alterations of substrate utilization are partly involved in development of insulin resistance in GDM. Fetuses born to such mothers have shown low umbilical vein oxygen saturation and low oxygen content and increased lactate concentrations. These changes may certainly reflect enhanced fetal metabolism as a result of hyperglycaemia and hyperinsulinemia and therefore, these fetuses deserve intense surveillance at term and during delivery. Ideally, HbA1c should be maintained below 5% during their first trimesters and below 6% during third trimester. We planned to investigate GDM women for their HbA1c levels too. Aim To know if there is any alteration in blood lactate and/or HbA1c levels and to know if there is any correlation between these two parameters in GDM pregnancies, in comparison with the previous studies which measured lactate in cord blood and placental vessels of GDM women. Materials and Methods It was a hospital based prospective study on 40 women with gestational diabetes and 40 age-matched normal pregnant women. We analysed the biochemical and metabolic mileau in these women by estimating venous blood lactate and HbA1c levels. We paid special attention to follow them up regarding maternal complications if any and perinatal outcomes. The independent samples t-test and Pearson’s correlation test were applied. Results GDM mothers showed significantly higher lactate and HbA1c levels than normal pregnant women, both with p<0.001. Blood pressure and fetal birth weight were also significantly higher in GDM group than Normal Pregnant (NP) group, both with p-values of <0.001. Further, this increased lactate levels showed significant positive correlation with HbA1c, blood pressure and fetal birth weight. Conclusion Maternal blood lactate and HbA1c levels have a

  6. Fetal hemoglobin in sickle cell anemia.

    PubMed

    Akinsheye, Idowu; Alsultan, Abdulrahman; Solovieff, Nadia; Ngo, Duyen; Baldwin, Clinton T; Sebastiani, Paola; Chui, David H K; Steinberg, Martin H

    2011-07-07

    Fetal hemoglobin (HbF) is the major genetic modulator of the hematologic and clinical features of sickle cell disease, an effect mediated by its exclusion from the sickle hemoglobin polymer. Fetal hemoglobin genes are genetically regulated, and the level of HbF and its distribution among sickle erythrocytes is highly variable. Some patients with sickle cell disease have exceptionally high levels of HbF that are associated with the Senegal and Saudi-Indian haplotype of the HBB-like gene cluster; some patients with different haplotypes can have similarly high HbF. In these patients, high HbF is associated with generally milder but not asymptomatic disease. Studying these persons might provide additional insights into HbF gene regulation. HbF appears to benefit some complications of disease more than others. This might be related to the premature destruction of erythrocytes that do not contain HbF, even though the total HbF concentration is high. Recent insights into HbF regulation have spurred new efforts to induce high HbF levels in sickle cell disease beyond those achievable with the current limited repertory of HbF inducers.

  7. Small angle neutron scattering studies of HbA in concentrated solutions.

    PubMed Central

    Krueger, S; Chen, S H; Hofrichter, J; Nossal, R

    1990-01-01

    Differential cross-sections for neutrons scattered by normal human hemoglobin have been determined over the range of concentrations from 2 to approximately 35 weight percent. Data are compared with structure factors calculated from models of monodisperse hard spheres interacting through a screened Coulomb potential. Good agreement is noted when the volume fraction eta is adjusted during multivariate fitting of data, but the fitted value of eta is always lower than expected from the known Hb concentration of the samples. Calculations of cross-sections for polydisperse scatterers suggest that the samples may contain oligomers of the fundamental tetrameric Hb molecule. PMID:2207261

  8. The correlations of glycated hemoglobin and carbohydrate metabolism parameters with heart rate variability in apparently healthy sedentary young male subjects

    PubMed Central

    Cherkas, Andriy; Abrahamovych, Orest; Golota, Sergii; Nersesyan, Armen; Pichler, Christoph; Serhiyenko, Victoria; Knasmüller, Siegfried; Zarkovic, Neven; Eckl, Peter

    2015-01-01

    Introduction Sedentary lifestyle is a major risk factor for diabetes, cardiovascular and many other age-related diseases. Heart rate variability (HRV) reflects the function of regulatory systems of internal organs and may sensitively indicate early metabolic disturbances. We hypothesize that quantitative and qualitative changes of HRV in young subjects may reflect early metabolic derangements responsible for further development of clinically significant disease. Aim The aim of our study was to determine whether the parameters of carbohydrate metabolism (fasting blood glucose, HBA1c and surrogate insulin sensitivity/resistance indices) correlate with anthropometric data and HRV. Methods The study group consisted of 30 healthy sedentary male subjects aged 20–40, nonsmokers, mainly office and research employees, medical staff and students. Athletes, actively training more than one hour per week, severely obese and men of physical work were excluded from the study. HRV parameters were derived from short term ECG records (five minutes intervals) in supine position and during orthostatic test. Anthropometric data included height, weight, body mass index (BMI), age and body composition (estimation by bioelectric impedance method). The fasting blood glucose, insulin and C-peptide, homeostatic model assessment (HOMA-IR) index and glycated hemoglobin (HbA1c) were evaluated. Linear correlation coefficient (r) was calculated using Statistica 10.0 software. Results and discussion HOMA-IR index correlated positively with body weight, visceral fat and BMI (p=0.047, 0.027 and 0.017 respectively). In supine position pNN50 positively correlated with glucose/insulin ratio (p=0.011) and heart rate with HOMA-IR (p=0.006). In orthostatic test negative correlations of HBA1c with standard deviation, total and low frequency power were determined (p=0.034, 0.400 and 0.403 respectively), which indicates a gradual worsening of functional capacity of cardiovascular system with low

  9. Modelling the Relative Contribution of Fasting and Post-Prandial Plasma Glucose to HbA1c in Healthy and Type 2 Diabetic Subjects

    ERIC Educational Resources Information Center

    Ollerton, Richard L.; Luzio, Steven D.; Owens, David R.

    2004-01-01

    Glycated haemoglobin (HbA1c) is regarded as the gold standard of glucose homeostasis assessment in diabetes. There has been much discussion in recent medical literature of experimental results concerning the relative contribution of fasting and post-prandial glucose levels to the value of HbA1c. A mathematical model of haemoglobin glycation is…

  10. HbA(1c) diagnostic categories and beta-cell function relative to insulin sensitivity in overweight/obese adolescents

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The recommended HbA1c diagnostic categories remain controversial and their utility in doubt in pediatrics. We hypothesized that alterations in the pathophysiologic mechanisms of type 2 diabetes may be evident in the American Diabetes Association recommended at-risk/prediabetes category (HbA(1c) 5.7 ...

  11. The difference between oats and beta-glucan extract intake in the management of HbA1c, fasting glucose and insulin sensitivity: a meta-analysis of randomized controlled trials.

    PubMed

    He, Li-xia; Zhao, Jian; Huang, Yuan-sheng; Li, Yong

    2016-03-01

    Increasing oats and beta-glucan extract intake has been associated with improved glycemic control, which is associated with the reduction in the development of diabetes. This study aims to assess the different effects between oat (whole and bran) and beta-glucan extract intake on glycemic control and insulin sensitivity. PubMed, Embase, Medline, The Cochrane Library, CINAHL and Web of Science were searched up to February 2014. We included randomized controlled trials with interventions that lasted at least four weeks that compared oats and beta-glucan (extracted from oats or other sources) intake with a control. A total of 1351 articles were screened for eligibility, and relevant data were extracted from 18 studies (n = 1024). Oat product dose ranged from 20 g d(-1) to 136 g d(-1), and beta-glucan extract dose ranged from 3 g d(-1) to 10 g d(-1). Compared with the control, oat intake resulted in a greater decrease in fasting glucose and insulin of subjects (P < 0.05), but beta-glucan extract intake did not. Furthermore, oat intake resulted in a greater decrease in glycosylated hemoglobin (HbA1c) (P < 0.001, I(2) = 0%) and fasting glucose (P < 0.001, I(2) = 68%) after removing one study using a concentrate and a different design and fasting insulin of type 2 diabetes (T2D) (P < 0.001, I(2) = 0%). The intake of oats and beta-glucan extracted from oats were effective in decreasing fasting glucose (P = 0.007, I(2) = 91%) and fasting insulin of T2D (P < 0.001, I(2) = 0%) and tented to lower HbA1c (P = 0.09, I(2) = 92%). Higher consumption of whole oats and oat bran, but not oat or barley beta-glucan extracts, are associated with lower HbA1c, fasting glucose and fasting insulin of T2D, hyperlipidaemic and overweight subjects, especially people with T2D, which supports the need for clinical trials to evaluate the potential role of oats in approaching to the management of glycemic control and insulin sensitivity of diabetes or metabolic syndrome subjects.

  12. Treatment with insulin analogs, especially Glargine and Lispro, associates with better renal function and higher hemoglobin levels in Type 1 diabetic patients with impaired kidney function

    PubMed Central

    Hasslacher, Christoph; Kulozik, Felix; Lorenzo Bermejo, Justo

    2016-01-01

    Objectives: The influence of type of insulin treatment - insulin analogs versus human insulin - on the development of diabetes related vascular complications has been sparsely investigated. We examine here possible differences regarding kidney function and hemoglobin levels. Methods: Multiple linear regression was used to investigate the relationship between the following characteristics measured in 509 type 1 diabetic patients who were recruited in an outpatient practice: current clinical status and treatment modalities, type of injected insulin and the routine laboratory parameters hemoglobin, HbA1c, serum creatinine, eGFR, hs CRP and urinary albumin/creatinine ratio. Results: Compared with human insulin, multiple regression analysis taking into account possible confounders revealed that treatment with insulin analogs was associated with increased eGFR (+7.1 ml/min; P=0.0002), lower urinary albumin/creatinine ratio (ratio logarithm -0.4; P=0.003) and higher hemoglobin concentration (+0.31 g/dl; P=0.04). Stratification by type of insulin showed the best renal status for treatment with insulins Glargine and Lispro. Differences were consistent both for patients with normal (eGFR → 90 ml/min) and with an impaired (eGFR ← 90 ml/min) kidney function. Conclusions: Present results suggest that treatment of type 1 diabetic patients with normal and impaired renal function with insulin analogs, especially Glargine and Lispro, is associated with better kidney function, lower urinary albumin/creatinine ratio and lower hemoglobin concentration compared to therapy with human insulin. If confirmed by other studies, treatment with insulin analogs may be a further possibility in delaying progression of nephropathy and in preventing early hemoglobin decline. PMID:27540462

  13. Enhanced nitrite reductase activity associated with the haptoglobin complexed hemoglobin dimer: functional and antioxidative implications.

    PubMed

    Roche, Camille J; Dantsker, David; Alayash, Abdu I; Friedman, Joel M

    2012-06-30

    The presence of acellular hemoglobin (Hb) within the circulation is generally viewed as a pathological state that can result in toxic consequences. Haptoglobin (Hp), a globular protein found in the plasma, binds with high avidity the αβ dimers derived from the dissociation of Hb tetramer and thus helps clear free Hb. More recently there have been compelling indications that the redox properties of the Hp bound dimer (Hb-Hp) may play a more active role in controlling toxicity by limiting the potential tissue damage caused by propagation of the free-radicals generated within the heme containing globin chains. The present study further examines the potential protective effect of Hp through its impact on the production of nitric oxide (NO) from nitrite through nitrite reductase activity of the Hp bound αβ Hb dimer. The presented results show that the Hb dimer in the Hb-Hp complex has oxygen binding, CO recombination and spectroscopic properties consistent with an Hb species having properties similar to but not exactly the same as the R quaternary state of the Hb tetramer. Consistent with these observations is the finding that the initial nitrite reductase rate for Hb-Hp is approximately ten times that of HbA under the same conditions. These results in conjunction with the earlier redox properties of the Hb-Hp are discussed in terms of limiting the pathophysiological consequences of acellular Hb in the circulation.

  14. Alkaline Bohr effect of bird hemoglobins: the case of the flamingo.

    PubMed

    Sanna, Maria Teresa; Manconi, Barbara; Podda, Gabriella; Olianas, Alessandra; Pellegrini, Mariagiuseppina; Castagnola, Massimo; Messana, Irene; Giardina, Bruno

    2007-08-01

    The hemoglobin (Hb) substitution His-->Gln at position alpha89, very common in avian Hbs, is considered to be responsible for the weak Bohr effect of avian Hbs. Phoenicopterus ruber ruber is one of the few avian Hbs that possesses His at alpha89, but it has not been functionally characterized yet. In the present study the Hb system of the greater flamingo (P. ruber roseus), a bird that lives in Mediterranean areas, has been investigated to obtain further insight into the role played by the alpha89 residue in determining the strong reduction of the Bohr effect. Functional analysis of the two purified Hb components (HbA and HbD) of P. ruber roseus showed that both are characterized by high oxygen affinity in the absence of organic phosphates, a strong modulating effect of inositol hexaphosphate, and a reduced Bohr effect. Indeed, in spite of the close phylogenetic relationship between the two flamingo species, structural analysis based on tandem mass spectrometry of the alpha(A) chain of P. ruber roseus Hb showed that a Gln residue is present at position alpha89.

  15. The postnatal decline of hemoglobin F synthesis in normal full-term infants.

    PubMed

    Bard, H

    1975-02-01

    Studies were carried out during the 1st yr of life in normal infants born at term to determine the proportions of fetal hemoglobin (Hb F) and adult hemoglobin (Hb A) being synthesized, in order to describe the complete switchover from Hb F to Hb A synthesis during postnatal life. 53 blood samples from 37 infants were incubated in an amino acid mixture containing [14C]leucine and chromatographed on DEAE-Sephadex for separation of Hb F and Hb A fractions. The completeness of the CEAE-Sephadex separation of Hb A and Hb F at an age when the major portion of synthesis was of the adult type of hemoglobin was confirmed by globin chain chromatography with the use of carboxylmethyl cellulose. There was a rapid decline in Hb F synthesis postnatally until 16-20 wk of age when levels of 3.2% plus or minus SD 2.1% were reached. By combining this data with that previously published, the complete switchover from Hb F to Hb A synthesis can be described in humans in relation to postconceptional age. It follows a sigmoid curve; the steep portion, which lies between the 30th and 52nd postconceptional week, is preceded and follwoed by plateaus averaging 95% and 7% Hb F synthesis, respectively.

  16. Transcription factors LRF and BCL11A independently repress expression of fetal hemoglobin.

    PubMed

    Masuda, Takeshi; Wang, Xin; Maeda, Manami; Canver, Matthew C; Sher, Falak; Funnell, Alister P W; Fisher, Chris; Suciu, Maria; Martyn, Gabriella E; Norton, Laura J; Zhu, Catherine; Kurita, Ryo; Nakamura, Yukio; Xu, Jian; Higgs, Douglas R; Crossley, Merlin; Bauer, Daniel E; Orkin, Stuart H; Kharchenko, Peter V; Maeda, Takahiro

    2016-01-15

    Genes encoding human β-type globin undergo a developmental switch from embryonic to fetal to adult-type expression. Mutations in the adult form cause inherited hemoglobinopathies or globin disorders, including sickle cell disease and thalassemia. Some experimental results have suggested that these diseases could be treated by induction of fetal-type hemoglobin (HbF). However, the mechanisms that repress HbF in adults remain unclear. We found that the LRF/ZBTB7A transcription factor occupies fetal γ-globin genes and maintains the nucleosome density necessary for γ-globin gene silencing in adults, and that LRF confers its repressive activity through a NuRD repressor complex independent of the fetal globin repressor BCL11A. Our study may provide additional opportunities for therapeutic targeting in the treatment of hemoglobinopathies.

  17. Transcription factors LRF and BCL11A independently repress expression of fetal hemoglobin

    PubMed Central

    Masuda, Takeshi; Wang, Xin; Maeda, Manami; Canver, Matthew C.; Sher, Falak; Funnell, Alister P. W.; Fisher, Chris; Suciu, Maria; Martyn, Gabriella E.; Norton, Laura J.; Zhu, Catherine; Kurita, Ryo; Nakamura, Yukio; Xu, Jian; Higgs, Douglas R.; Crossley, Merlin; Bauer, Daniel E.; Orkin, Stuart H.; Kharchenko, Peter V.; Maeda, Takahiro

    2016-01-01

    Genes encoding human β-type globin undergo a developmental switch from embryonic to fetal to adult-type expression. Mutations in the adult form cause inherited hemoglobinopathies or globin disorders, including sickle cell disease and thalassemia. Some experimental results have suggested that these diseases could be treated by induction of fetal-type hemoglobin (HbF). However, the mechanisms that repress HbF in adults remain unclear. We found that the LRF/ZBTB7A transcription factor occupies fetal γ-globin genes and maintains the nucleosome density necessary for γ-globin gene silencing in adults, and that LRF confers its repressive activity through a NuRD repressor complex independent of the fetal globin repressor BCL11A. Our study may provide additional opportunities for therapeutic targeting in the treatment of hemoglobinopathies. PMID:26816381

  18. Relationship of Baseline Hemoglobin Level with Serum Ferritin, Postphlebotomy Hemoglobin Changes, and Phlebotomy Requirements among HFE C282Y Homozygotes.

    PubMed

    Mousavi, Seyed Ali; Mahmood, Faiza; Aandahl, Astrid; Knutsen, Teresa Risopatron; Llohn, Abid Hussain

    2015-01-01

    Objectives. We aimed to examine whether baseline hemoglobin levels in C282Y-homozygous patients are related to the degree of serum ferritin (SF) elevation and whether patients with different baseline hemoglobin have different phlebotomy requirements. Methods. A total of 196 patients (124 males and 72 females) who had undergone therapeutic phlebotomy and had SF and both pre- and posttreatment hemoglobin values were included in the study. Results. Bivariate correlation analysis suggested that baseline SF explains approximately 6 to 7% of the variation in baseline hemoglobin. The results also showed that males who had higher (≥150 g/L) baseline hemoglobin levels had a significantly greater reduction in their posttreatment hemoglobin despite requiring fewer phlebotomies to achieve iron depletion than those who had lower (<150 g/L) baseline hemoglobin, regardless of whether baseline SF was below or above 1000 µg/L. There were no significant differences between hemoglobin subgroups regarding baseline and treatment characteristics, except for transferrin saturation between male subgroups with SF above 1000 µg/L. Similar differences were observed when females with higher (≥138 g/L) baseline hemoglobin were compared with those with lower (<138 g/L) baseline hemoglobin. Conclusion. Dividing C282Y-homozygous patients into just two subgroups according to the degree of baseline SF elevation may obscure important subgroup variations.

  19. Universal Metastability of Sickle Hemoglobin Polymerization

    PubMed Central

    Weng, Weijun; Aprelev, Alexey; Briehl, Robin W.; Ferrone, Frank A.

    2008-01-01

    Summary Sickle hemoglobin (HbS) polymerization occurs when deoxy HbS concentration exceeds a well-defined solubility. In experiments using sickle hemoglobin droplets suspended in oil, it has been shown that when polymerization ceases the monomer concentration is above equilibrium solubility. We find that the final concentration in uniform bulk solutions (i.e. with negligible boundaries) agrees with the droplet measurements, and both exceed the expected solubility. To measure hemoglobin in uniform solutions we used modulated excitation of trace amounts of CO in gels of HbS. In this method, a small amount of CO is introduced to a spatially uniform deoxyHb sample, so that less than 2% of the sample is liganded. The liganded fraction is repeatedly photolyzed and the rate of recombination allows the concentration of deoxyHbS in the solution phase to be determined, even if polymers have formed. Both uniform and droplet samples exhibit the same quantitative behavior, exceeding solubility by an amount that depends on the initial concentration of the sample, as well as conditions under which the gel was formed. We hypothesize that the early termination of polymerization is due to the obstruction in polymer growth, which is consistent with the observation that pressing on slides lowers the final monomer concentration, making it closer to solubility. The thermodynamic solubility in free solution is thus only achieved in conditions with low polymer density or under external forces (such as found in sedimentation) that disrupt polymers. Since we find that only about 67% of the expected polymer mass forms, this result will impact any analysis predicated on predicting the polymer fraction in a given experiment. PMID:18308336

  20. Preparation of Hemoglobin-Containing Microcapsules.

    DTIC Science & Technology

    1981-06-01

    were suspended in saline for storage in a refrigerator. Although in these microencapsulation experiments, the Hb was not denatured, the microcapsules ... microencapsulated Hb, l.O-ml sample of the microcapsule suspension was diluted with 10 ml 0.9% NaCI. The absorption spectrum was taken immediately after dilution...AD A135 634 PREPARATION OF HEMOGLOBIN CONTA NING MICROCAPSULES (U) I/ ,R 224 AM OS NTERNATIDNAL MENOPARKO CA REYES AUNN8 SRI-2254-1 DAMD17-80-C-01?7

  1. Neutral changes during divergent evolution of hemoglobins

    NASA Technical Reports Server (NTRS)

    Jukes, T. H.

    1978-01-01

    A comparison of the mRNAs for rabbit and human beta-hemoglobins shows that synonymous changes in codons have accumulated three times as rapidly as nucleotide replacements that produced changes in amino acids. This agrees with predictions based on the so-called neutral theory. In addition, seven codon changes that appear to be single-base changes (according to maximum parsimony) are actually two-base changes. This indicates that the construction of primordial sequences is of limited significance when based on inferences that assume minimum base changes for amino acid replacements.

  2. EHMT1 and EHMT2 inhibition induces fetal hemoglobin expression

    PubMed Central

    Renneville, Aline; Van Galen, Peter; Canver, Matthew C.; McConkey, Marie; Krill-Burger, John M.; Dorfman, David M.; Holson, Edward B.; Bernstein, Bradley E.; Orkin, Stuart H.; Bauer, Daniel E.

    2015-01-01

    Fetal hemoglobin (HbF, α2γ2) induction is a well-validated strategy for sickle cell disease (SCD) treatment. Using a small-molecule screen, we found that UNC0638, a selective inhibitor of EHMT1 and EHMT2 histone methyltransferases, induces γ-globin expression. EHMT1/2 catalyze mono- and dimethylation of lysine 9 on histone 3 (H3K9), raising the possibility that H3K9Me2, a repressive chromatin mark, plays a role in silencing γ-globin expression. In primary human adult erythroid cells, UNC0638 and EHMT1 or EHMT2 short hairpin RNA–mediated knockdown significantly increased γ-globin expression, HbF synthesis, and the percentage of cells expressing HbF. At effective concentrations, UNC0638 did not alter cell morphology, proliferation, or erythroid differentiation of primary human CD34+ hematopoietic stem and progenitor cells in culture ex vivo. In murine erythroleukemia cells, UNC0638 and Ehmt2 CRISPR/Cas9-mediated knockout both led to a marked increase in expression of embryonic β-globin genes Hbb-εy and Hbb-βh1. In primary human adult erythroblasts, chromatin immunoprecipitation followed by sequencing analysis revealed that UNC0638 treatment leads to genome-wide depletion in H3K9Me2 and a concomitant increase in the activating mark H3K9Ac, which was especially pronounced at the γ-globin gene region. In RNA-sequencing analysis of erythroblasts, γ-globin genes were among the most significantly upregulated genes by UNC0638. Further increase in γ-globin expression in primary human adult erythroid cells was achieved by combining EHMT1/2 inhibition with the histone deacetylase inhibitor entinostat or hypomethylating agent decitabine. Our data provide genetic and pharmacologic evidence that EHMT1 and EHMT2 are epigenetic regulators involved in γ-globin repression and represent a novel therapeutic target for SCD. PMID:26320100

  3. EHMT1 and EHMT2 inhibition induces fetal hemoglobin expression.

    PubMed

    Renneville, Aline; Van Galen, Peter; Canver, Matthew C; McConkey, Marie; Krill-Burger, John M; Dorfman, David M; Holson, Edward B; Bernstein, Bradley E; Orkin, Stuart H; Bauer, Daniel E; Ebert, Benjamin L

    2015-10-15

    Fetal hemoglobin (HbF, α2γ2) induction is a well-validated strategy for sickle cell disease (SCD) treatment. Using a small-molecule screen, we found that UNC0638, a selective inhibitor of EHMT1 and EHMT2 histone methyltransferases, induces γ-globin expression. EHMT1/2 catalyze mono- and dimethylation of lysine 9 on histone 3 (H3K9), raising the possibility that H3K9Me2, a repressive chromatin mark, plays a role in silencing γ-globin expression. In primary human adult erythroid cells, UNC0638 and EHMT1 or EHMT2 short hairpin RNA-mediated knockdown significantly increased γ-globin expression, HbF synthesis, and the percentage of cells expressing HbF. At effective concentrations, UNC0638 did not alter cell morphology, proliferation, or erythroid differentiation of primary human CD34(+) hematopoietic stem and progenitor cells in culture ex vivo. In murine erythroleukemia cells, UNC0638 and Ehmt2 CRISPR/Cas9-mediated knockout both led to a marked increase in expression of embryonic β-globin genes Hbb-εy and Hbb-βh1. In primary human adult erythroblasts, chromatin immunoprecipitation followed by sequencing analysis revealed that UNC0638 treatment leads to genome-wide depletion in H3K9Me2 and a concomitant increase in the activating mark H3K9Ac, which was especially pronounced at the γ-globin gene region. In RNA-sequencing analysis of erythroblasts, γ-globin genes were among the most significantly upregulated genes by UNC0638. Further increase in γ-globin expression in primary human adult erythroid cells was achieved by combining EHMT1/2 inhibition with the histone deacetylase inhibitor entinostat or hypomethylating agent decitabine. Our data provide genetic and pharmacologic evidence that EHMT1 and EHMT2 are epigenetic regulators involved in γ-globin repression and represent a novel therapeutic target for SCD.

  4. Multiple hemoglobins of the cutthroat trout, Salmo clarki.

    PubMed

    Southard, J N; Berry, C R; Farley, T M

    1986-07-01

    Nine hemoglobins were purified from blood of Salmo clarki by ion-exchange chromatography and preparative isoelectric focusing. The subunit structures of eight of the purified hemoglobins were studied by electrophoresis of globins in the presence of urea. Six are alpha 2 beta 2 tetramers while two appear to be heterotetramers of the type alpha alpha' beta 2 and alpha alpha' beta beta'. The effects of pH, nucleotides, and temperature on the oxygen equilibria of the purified hemoglobins were studied. Five hemoglobins with isoelectric points from 9.1 to 7.1 and one minor hemoglobin with an isoelectric point of 5.9 appear to have essentially identical oxygen binding properties. All have similar oxygen equilibria which are independent of pH and temperature and not affected by saturating amounts of ATP. Another minor hemoglobin with an isoelectric point below 5.9 has similar oxygen equilibria except for a possible pH dependence. Two hemoglobins, with isoelectric points of 6.5 and 6.4, have oxygen binding properties which are strongly pH and temperature dependent. Addition of ATP or GTP causes a large decrease in the oxygen affinity without affecting the cooperativity of oxygen binding. The effect of GTP is slightly greater than that of ATP. No significant differences were observed in the oxygen equilibria of these two hemoglobins. The red blood cells of S. clarki were found to contain large amounts of both ATP and GTP, with an ATP:GTP ratio of 3:1. Both nucleotides may be important modulators of hemoglobin oxygen affinity in S. clarki, in contrast to the situation in S. gairdneri, in which red blood cell GTP concentrations are considerably lower. The presence of six or possibly seven hemoglobins with identical oxygen binding properties in S. clarki suggests that, to a large extent, the physiological role of multiple hemoglobins in this species involves phenomena not directly related to the oxygen binding properties of the hemoglobins.

  5. Medical Aspects of Sickle Hemoglobin in Military Personnel

    PubMed Central

    Brodine, C. E.; Uddin, D. E.

    1977-01-01

    The Department of Defense (DOD) will soon issue a directive to test all incoming military personnel for the presence of hemoglobin S. The military testing program for hemoglobin S is an occupational medicine program. This report includes a discussion of armed services physical standards, a description of the Navy effort to evaluate an automated system for detection of hemoglobin S, and the proposed DOD directive. PMID:833894

  6. Characterization of the hemoglobin of the backswimmer Anisops deanei (Hemiptera).

    PubMed

    Wawrowski, Agnes; Matthews, Philip G D; Gleixner, Eva; Kiger, Laurent; Marden, Michael C; Hankeln, Thomas; Burmester, Thorsten

    2012-09-01

    While O(2)-binding hemoglobin-like proteins are present in many insects, prominent amounts of hemoglobin have only been found in a few species. Backswimmers of the genera Anisops and Buenoa (Notonectidae) have high concentrations of hemoglobin in the large tracheal cells of the abdomen. Oxygen from the hemoglobin is delivered to a gas bubble and controls the buoyant density, which enables the bugs to maintain their position without swimming and to remain stationary in the mid-water zone where they hunt for prey. We have obtained the cDNA sequences of three Anisops deanei hemoglobin chains by RT-PCR and RACE techniques. The deduced amino acid sequences show an unusual insertion of a single amino acid in the conserved helix E, but this does not affect protein stability or ligand binding kinetics. Recombinant A. deanei hemoglobin has an oxygen affinity of P(50) = 2.4 kPa (18 torr) and reveals the presence of a dimeric fraction or two different conformations. The absorption spectra demonstrate that the Anisops hemoglobin is a typical pentacoordinate globin. Phylogenetic analyses show that the backswimmer hemoglobins evolved within Heteroptera and most likely originated from an intracellular hemoglobin with divergent function.

  7. WAXS studies of the structural diversity of hemoglobin in solution.

    SciTech Connect

    Makowski, L.; Bardhan, J.; Gore, D.; Lal, J.; Mandava, S.; Park, S.; Rodi, D. J.; Ho, N. T.; Ho, C.; Fischetti, R. F.

    2011-01-01

    Specific ligation states of hemoglobin are, when crystallized, capable of taking on multiple quaternary structures. The relationship between these structures, captured in crystal lattices, and hemoglobin structure in solution remains uncertain. Wide-angle X-ray solution scattering (WAXS) is a sensitive probe of protein structure in solution that can distinguish among similar structures and has the potential to contribute to these issues. We used WAXS to assess the relationships among the structures of human and bovine hemoglobins in different liganded forms in solution. WAXS data readily distinguished among the various forms of hemoglobins. WAXS patterns confirm some of the relationships among hemoglobin structures that have been defined through crystallography and NMR and extend others. For instance, methemoglobin A in solution is, as expected, nearly indistinguishable from HbCO A. Interestingly, for bovine hemoglobin, the differences between deoxy-Hb, methemoglobin and HbCO are smaller than the corresponding differences in human hemoglobin. WAXS data were also used to assess the spatial extent of structural fluctuations of various hemoglobins in solution. Dynamics has been implicated in allosteric control of hemoglobin, and increased dynamics has been associated with lowered oxygen affinity. Consistent with that notion, WAXS patterns indicate that deoxy-Hb A exhibits substantially larger structural fluctuations than HbCO A. Comparisons between the observed WAXS patterns and those predicted on the basis of atomic coordinate sets suggest that the structures of Hb in different liganded forms exhibit clear differences from known crystal structure.

  8. 21 CFR 864.7470 - Glycosylated hemoglobin assay.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... diabetes and to determine the proper insulin dosage for a patient. Elevated levels of glycosylated hemoglobin indicate uncontrolled diabetes in a patient. (b) Classification. Class II (performance standards)....

  9. 21 CFR 864.7470 - Glycosylated hemoglobin assay.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... diabetes and to determine the proper insulin dosage for a patient. Elevated levels of glycosylated hemoglobin indicate uncontrolled diabetes in a patient. (b) Classification. Class II (performance standards)....

  10. 21 CFR 864.7470 - Glycosylated hemoglobin assay.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... diabetes and to determine the proper insulin dosage for a patient. Elevated levels of glycosylated hemoglobin indicate uncontrolled diabetes in a patient. (b) Classification. Class II (performance standards)....

  11. 21 CFR 864.7470 - Glycosylated hemoglobin assay.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... diabetes and to determine the proper insulin dosage for a patient. Elevated levels of glycosylated hemoglobin indicate uncontrolled diabetes in a patient. (b) Classification. Class II (performance standards)....

  12. 21 CFR 864.7470 - Glycosylated hemoglobin assay.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... diabetes and to determine the proper insulin dosage for a patient. Elevated levels of glycosylated hemoglobin indicate uncontrolled diabetes in a patient. (b) Classification. Class II (performance standards)....

  13. Properties of Hemoglobin Decolorized with a Histidine-Specific Protease.

    PubMed

    Shi, Jing; de Roos, Andre; Schouten, Olaf; Zheng, Chaoya; Vink, Collin; Vonk, Brenda; Kliphuis, Annette; Schaap, Albert; Edens, Luppo

    2015-06-01

    This study investigated the application of Aspergilloglutamic peptidase (AGP) on porcine hemoglobin decolorization. AGP from fungus Aspergillus niger is identified to possess a high preference towards the histidine residues. As histidine residues in hemoglobin are known to coordinate the heme group within the globin molecule, we therefore hypothesized that incubating hemoglobin with a histidine-specific protease would efficiently separate the non-heme peptides from the heme-enriched peptides with a minimum degree of hydrolysis. AGP-decolored porcine hemoglobin hydrolysates were assessed on their functional (for example, color, emulsification, foaming, and water binding) and sensory properties. The results were compared with commercially available blood-derived proteins (subtilisin-decolored hemoglobin hydrolysates and plasma protein). It was observed that AGP is able to effectively decolor hemoglobin. The degree of hydrolysis (DH) increased less than 3% using AGP to achieve 90% color reduction of hemoglobin, whereas a DH increase of more than 20% is needed using subtilisin. The AGP-decolored hemoglobin hydrolysates (AGP-Hb) possess good emulsification, foaming, and water binding properties, which are better or comparable with the plasma protein, and much better than the subtilisin-decolored hemoglobin hydrolysates (subtilisin-Hb). The model canned meat with addition of AGP-Hb showed the highest value in hardness, springiness, and chewiness from the texture analysis. Furthermore, the canned meat with AGP-Hb was found to have a better sensory profile than the ones with addition of subtilisin-Hb and plasma protein.

  14. Hemoglobin alpha in the blood vessel wall

    PubMed Central

    Butcher, Joshua T.; Johnson, Tyler; Beers, Jody; Columbus, Linda; Isakson, Brant E

    2014-01-01

    Hemoglobin has been studied and well haracterized in red blood cells for over one hundred years. However, new work has indicated that the hemoglobin alpha subunit (Hbα) is also found within the blood vessel wall, where it appears to localize at the myoendothelial junction (MEJ) and plays a role in regulating nitric oxide (NO) signaling between endothelium and smooth muscle. This discovery has created a new paradigm for control of endothelial nitric oxide synthase activity, nitric oxide diffusion, and ultimately, control of vascular tone and blood pressure. This review will discuss the current knowledge of hemoglobin’s properties as a gas exchange molecule in the blood stream, and extrapolate the properties of Hbα biology to the MEJ signaling domain. Specifically, we propose that Hbα is present at the MEJ to regulate NO release and diffusion in a restricted physical space, which would have powerful implications for the regulation of blood flow in peripheral resistance arteries. PMID:24832680

  15. Effects of canagliflozin on body weight and relationship to HbA1c and blood pressure changes in patients with type 2 diabetes

    PubMed Central

    Stenlöf, Kaj; Leiter, Lawrence A.; Wilding, John P. H.; Blonde, Lawrence; Polidori, David; Xie, John; Sullivan, Daniel; Usiskin, Keith; Canovatchel, William; Meininger, Gary

    2016-01-01

    Aims/hypothesis Canagliflozin, a sodium glucose co-transporter 2 inhibitor, reduces HbA1c, body weight and systolic BP (SBP) in patients with type 2 diabetes. As weight loss is known to reduce both HbA1c and SBP, these analyses were performed to evaluate the contribution of weight loss resulting from treatment with canagliflozin to HbA1c and SBP reductions in patients with type 2 diabetes. Methods Pooled data from four placebo-controlled Phase 3 studies (N=2,250) in patients with type 2 diabetes were used in the analyses. In each study, patients were treated with placebo, canagliflozin 100 mg or canagliflozin 300 mg, once daily for 26 weeks. Changes from baseline in body weight, HbA1c and SBP were measured at week 26, and the contribution of weight loss to the lowering of HbA1c and SBP was obtained using ANCOVA. Results Canagliflozin 100 and 300 mg reduced mean body weight, HbA1c and SBP compared with placebo (p<0.001 for each), and more patients had body-weight reductions >0%, ≥5% and ≥10% with canagliflozin treatment than with placebo. Weight-loss-independent and weight-loss-associated mechanisms contributed to HbA1c and SBP lowering with canagliflozin: ~85% of HbA1c lowering and ~60% of SBP lowering was independent of weight loss. Conclusions/interpretation In patients with type 2 diabetes, canagliflozin provided clinically meaningful body-weight reductions, and the weight loss contributed to reductions in HbA1c and SBP. Trial registration ClinicalTrials.gov NCT01081834; NCT01106625; NCT01106677; and NCT01106690 PMID:25813214

  16. The Effect of Periodontal Treatment on Hemoglobin A1c Levels of Diabetic Patients: A Systematic Review and Meta-Analysis

    PubMed Central

    Wang, Xingxing; Han, Xu; Guo, Xiaojing; Luo, Xiaolong; Wang, Dalin

    2014-01-01

    Background There is growing evidence that periodontal treatment may affect glycemic control in diabetic patients. And several systematic reviews have been conducted to assess the effect of periodontal treatment on diabetes outcomes. Researches of this aspect are widely concerned, and several new controlled trials have been published. The aim of this study was to update the account for recent findings. Methods A literature search (until the end of January 2014) was carried out using various databases with language restriction to English. A randomized controlled trial (RCT) was selected if it investigated periodontal therapy for diabetic subjects compared with a control group received no periodontal treatment for at least 3 months of the follow-up period. The primary outcome was hemoglobin A1c (HbA1c), and secondary outcomes were periodontal parameters included probing pocket depth (PPD) and clinical attachment level (CAL). Results Ten trials of 1135 patients were included in the analysis. After the follow-up of 3 months, treatment substantially lowered HbA1c compared with no treatment after periodontal therapy (–0.36%, 95%CI, −0.52% to −0.19%, P<0.0001). Clinically substantial and statistically significant reduction of PPD and CAL were found between subjects with and without treatment after periodontal therapy (PPD −0.42 mm, 95%CI: −0.60 to −0.23, P<0.00001; CAL −0.34 mm, 95%CI: −0.52 to −0.16, P = 0.0002). And there is no significant change of the level of HbA1c at the 6-month comparing with no treatment (–0.30%, 95%CI, −0.69% to 0.09%, P = 0.13). Conclusions Periodontal treatment leads to the modest reduction in HbA1c along with the improvement of periodontal status in diabetic patients for 3 months, and this result is consistent with previous systematic reviews. And the effect of periodontal treatment on HbA1c cannot be observed at 6-month after treatment. PMID:25255331

  17. The Effect of Non-surgical Periodontal Therapy on Hemoglobin A1c Levels in Persons with Type 2 Diabetes and Chronic Periodontitis: A Randomized Clinical Trial

    PubMed Central

    Engebretson, Steven P.; Hyman, Leslie G.; Michalowicz, Bryan S.; Schoenfeld, Elinor R.; Gelato, Marie C.; Hou, Wei; Seaquist, Elizabeth R.; Reddy, Michael S.; Lewis, Cora E.; Oates, Thomas W.; Tripathy, Devjit; Katancik, James A.; Orlander, Philip R.; Paquette, David W.; Hanson, Naomi Q.; Tsai, Michael Y.

    2014-01-01

    Importance Chronic periodontitis, a destructive inflammatory disorder of the supporting structures of the teeth, is prevalent in patients with diabetes. Limited evidence suggests that periodontal therapy may improve glycemic control. Objective To determine if non-surgical periodontal treatment reduces hemoglobin A1c (HbA1c) in persons with type 2 diabetes (DM) and moderate to advanced chronic periodontitis. Design, Setting and Participants The Diabetes and Periodontal Therapy Trial (DPTT) is a 6-month, single-masked, randomized, multi-center clinical trial. Participants had DM, were taking stable doses of medications, had HbA1c ≥7% and <9%, and untreated periodontitis. Five hundred fourteen participants were enrolled between November 2009 and March 2012 from diabetes and dental clinics and communities affiliated with five academic medical centers. Intervention The treatment group (n=257) received scaling and root planing plus chlorhexidine oral rinse at baseline, and supportive periodontal therapy at three and six months. The control group (n=257) received no treatment for six months. Main Outcome Measure Difference in HbA1c change from baseline between groups at six months. Secondary outcomes included changes in probing pocket depths, clinical attachment loss, bleeding on probing, gingival index, fasting glucose, and the Homeostasis Model Assessment (HOMA2). Results Enrollment was stopped early due to futility. At 6 months, the periodontal therapy group increased HbA1c 0.17% (1.0) (mean (SD)) compared to 0.11% (1.0) in the control group, with no significant difference between groups based on a linear regression model adjusting for clinical site (mean difference = -0.05%; 95% Confidence Interval (CI): -0.23%, 0.12%; p=0.55). Probing depth, clinical attachment loss, bleeding on probing and gingival index measures improved in the treatment group compared to the control group at six months with adjusted between-group differences of 0.33mm (95% CI: 0.26, 0.39), 0

  18. Long-Term Single and Joint Effects of Excessive Daytime Napping on the HOMA-IR Index and Glycosylated Hemoglobin: A Prospective Cohort Study.

    PubMed

    Li, Xue; Pang, Xiuyu; Zhang, Qiao; Qu, Qiannuo; Hou, Zhigang; Liu, Zhipeng; Lv, Lin; Na, Guanqiong; Zhang, Wei; Sun, Changhao; Li, Ying

    2016-02-01

    This prospective cohort study was conducted to assess the duration of daytime napping and its effect combined with night sleep deprivation on the risk of developing high HOMA-IR (homeostasis model assessment of insulin resistance) index and disadvantageous changes in glycosylated hemoglobin (HbA1c) levels.A total of 5845 diabetes-free subjects (2736 women and 3109 men), 30 to 65 years of age, were targeted for this cohort study since 2008. Multiple adjusted Cox regression models were performed to evaluate the single and joint effects of daytime napping on the risk of an elevated HbA1c level and high HOMA-IR index.After an average of 4.5 years of follow-up, >30 minutes of daytime napping was significantly associated with an increased risk of an elevated HbA1c level (>6.5%) in men and women (all P trend < 0.05). Hazard ratios (HRs) for an HbA1c level between 5.7% and 6.4% were also significant in the entire cohort and women, but nonsignificant in men. HRs (95% confidence interval, CIs) for the high HOMA-IR index in the entire cohort, men, and women were 1.33 (1.10-1.62), 1.46 (1.08-1.98), and 1.47 (1.12-1.91), respectively. The combination of sleep deprivation with no naps or >30 minutes napping and the combination of no sleep deprivation with >30 minutes daytime napping were all associated with an HbA1c level >6.5% (HR = 2.08, 95% CI = 1.24-3.51; HR = 4.00, 95% CI = 2.03-7.90; and HR = 2.05, 95% CI = 1.29-3.27, respectively). No sleep deprivation combined with >30 minutes daytime napping correlated with a high risk of an HbA1c level between 5.7% and 6.4% and high HOMA-IR index (HR = 2.12, 95% CI = 1.48-3.02; and HR = 1.35, 95% CI = 1.10-1.65, respectively).Daytime napping >30 minutes was associated with a high risk of an elevated HbA1c level and high HOMA-IR index. No sleep deprivation combined with napping >30 minutes carries a risk of abnormal glucose metabolism. Sleep deprivation combined with brief daytime napping <30

  19. Implementation of the HbA1c IFCC unit --from the laboratory to the consumer: The New Zealand experience.

    PubMed

    Florkowski, Christopher; Crooke, Michael; Reed, Maxine

    2014-05-15

    In 2007, an international consensus statement recommended that HbA1c results should be reported world-wide in IFCC units (mmol/mol) and also the more familiar derived percentage units using a master equation. In New Zealand, the HbA1c IFCC units have been successfully implemented and used exclusively since 3rd October 2011 (following a 2 year period of reporting both units) for both patient monitoring and the diagnosis of diabetes, with a diagnostic cut-off of ≥50 mmol/mol. The consultation process in New Zealand dates back to 2003, well before the international recommendations were made. It reflects the close cooperation between the clinical and laboratory communities in New Zealand, particularly through the agency of the New Zealand Society for the Study of Diabetes (NZSSD), a key organisation in New Zealand open to all those involved in the care of people with diabetes and the national advisory body on scientific and clinical diabetes care and standards. There was a phased process of consultation designed to increase familiarity and comfort with the new units and the final step was coupled with the adoption of HbA1c as a diagnostic test with some evidence-based pragmatism around using the rounded cut-off. Genuine clinical engagement is vital in such a process.

  20. Heterogeneous behavior of lipids according to HbA1c levels undermines the plausibility of metabolic syndrome in type 1 diabetes: data from a nationwide multicenter survey

    PubMed Central

    2012-01-01

    Background Cardiovascular risk factors (CVRF) may cluster in type 1 diabetes, analogously to the metabolic syndrome described in type 2 diabetes. The threshold of HbA1c above which lipid variables start changing behavior is unclear. This study aims to 1) assess the behavior of dyslipidemia according to HbA1c values; 2) detect a threshold of HbA1c beyond which lipids start to change and 3) compare the clustering of lipids and other non-lipid CVRF among strata of HbA1c individuals with type 1 diabetes. Methods Effects of HbA1c quintiles (1st: ≤7.4%; 2nd: 7.5-8.5%; 3rd: 8.6-9.6%; 4th: 9.7-11.3%; and 5th: >11.5%) and covariates (gender, BMI, blood pressure, insulin daily dose, lipids, statin use, diabetes duration) on dyslipidemia were studied in 1275 individuals from the Brazilian multi-centre type 1 diabetes study and 171 normal controls. Results Body size and blood pressure were not correlated to lipids and glycemic control. OR (99% CI) for high-LDL were 2.07 (1.21-3.54) and 2.51 (1.46-4.31), in the 4th and 5th HbA1c quintiles, respectively. Hypertriglyceridemia increased in the 5th quintile of HbA1c, OR 2.76 (1.20-6.37). OR of low-HDL-cholesterol were 0.48 (0.24-0.98) and 0.41 (0.19-0.85) in the 3rd and 4th HbA1c quintiles, respectively. HDL-cholesterol correlated positively (0.437) with HbA1c in the 3rd quintile. HDL-cholesterol and insulin dose correlated inversely in all levels of glycemic control. Conclusions Correlation of serum lipids with HbA1c is heterogeneous across the spectrum of glycemic control in type 1 diabetes individuals. LDL-cholesterol and triglycerides worsened alongside HbA1c with distinct thresholds. Association of lower HDL-cholesterol with higher daily insulin dose is consistent and it points out to a role of exogenous hyperinsulinemia in the pathophysiology of the CVRF clustering. These data suggest diverse pathophysiological processes depending on HbA1c, refuting a unified explanation for cardiovascular risk in type 1 diabetes. PMID

  1. Glycaemic control is harder to achieve than blood pressure or lipid control in Irish adults with type 1 diabetes.

    PubMed

    Cotter, T G; Dinneen, S F; Healy, D A; Bell, M J; Cunningham, A; O'Shea, P M; Dunne, F; O'Brien, T; Finucane, F M

    2014-12-01

    We sought to determine the attainment of targets for glycaemic control and vascular risk reduction in an Irish cohort of T1DM adults. Of 797 patients (53% male, mean age 40.3 ± 14.8 years, HbA1c 8.5 ± 1.6% (69.6 ± 17.8 mmol mol(-1))), 15%, 68% and 62% achieved targets for HbA1c, blood pressure and LDL cholesterol, respectively.

  2. Using Automated HbA1c Testing to Detect Diabetes Mellitus in Orthopedic Inpatients and Its Effect on Outcomes

    PubMed Central

    Ekinci, Elif I.; Kong, Alvin; Churilov, Leonid; Nanayakkara, Natalie; Chiu, Wei Ling; Sumithran, Priya; Djukiadmodjo, Frida; Premaratne, Erosha; Owen-Jones, Elizabeth; Hart, Graeme Kevin; Robbins, Raymond; Hardidge, Andrew; Johnson, Douglas; Baker, Scott T.; Zajac, Jeffrey D.

    2017-01-01

    Aims The prevalence of diabetes is rising, and people with diabetes have higher rates of musculoskeletal-related comorbidities. HbA1c testing is a superior option for diabetes diagnosis in the inpatient setting. This study aimed to (i) demonstrate the feasibility of routine HbA1c testing to detect the presence of diabetes mellitus, (ii) to determine the prevalence of diabetes in orthopedic inpatients and (iii) to assess the association between diabetes and hospital outcomes and post-operative complications in orthopedic inpatients. Methods All patients aged ≥54 years admitted to Austin Health between July 2013 and January 2014 had routine automated HbA1c measurements using automated clinical information systems (CERNER). Patients with HbA1c ≥6.5% were diagnosed with diabetes. Baseline demographic and clinical data were obtained from hospital records. Results Of the 416 orthopedic inpatients included in this study, 22% (n = 93) were known to have diabetes, 4% (n = 15) had previously unrecognized diabetes and 74% (n = 308) did not have diabetes. Patients with diabetes had significantly higher Charlson comorbidity scores compared to patients without diabetes (median, IQR; 1 [0,2] vs 0 [0,0], p<0.001). After adjusting for age, gender, comorbidity score and estimated glomerular filtration rate, no significant differences in the length of stay (IRR = 0.92; 95%CI: 0.79–1.07; p = 0.280), rates of intensive care unit admission (OR = 1.04; 95%CI: 0.42–2.60, p = 0.934), 6-month mortality (OR = 0.52; 95%CI: 0.17–1.60, p = 0.252), 6-month hospital readmission (OR = 0.93; 95%CI: 0.46–1.87; p = 0.828) or any post-operative complications (OR = 0.98; 95%CI: 0.53–1.80; p = 0.944) were observed between patients with and without diabetes. Conclusions Routine HbA1c measurement using CERNER allows for rapid identification of inpatients admitted with diabetes. More than one in four patients admitted to a tertiary hospital orthopedic ward have diabetes. No statistically

  3. Direct measurement of equilibrium constants for high-affinity hemoglobins.

    PubMed

    Kundu, Suman; Premer, Scott A; Hoy, Julie A; Trent, James T; Hargrove, Mark S

    2003-06-01

    The biological functions of heme proteins are linked to their rate and affinity constants for ligand binding. Kinetic experiments are commonly used to measure equilibrium constants for traditional hemoglobins comprised of pentacoordinate ligand binding sites and simple bimolecular reaction schemes. However, kinetic methods do not always yield reliable equilibrium constants with more complex hemoglobins for which reaction mechanisms are not clearly understood. Furthermore, even where reaction mechanisms are clearly understood, it is very difficult to directly measure equilibrium constants for oxygen and carbon monoxide binding to high-affinity (K(D) < 1 micro M) hemoglobins. This work presents a method for direct measurement of equilibrium constants for high-affinity hemoglobins that utilizes a competition for ligands between the "target" protein and an array of "scavenger" hemoglobins with known affinities. This method is described for oxygen and carbon monoxide binding to two hexacoordinate hemoglobins: rice nonsymbiotic hemoglobin and Synechocystis hemoglobin. Our results demonstrate that although these proteins have different mechanisms for ligand binding, their affinities for oxygen and carbon monoxide are similar. Their large affinity constants for oxygen, 285 and approximately 100 micro M(-1) respectively, indicate that they are not capable of facilitating oxygen transport.

  4. Computation Of Facilitated Transport of O2 In Hemoglobin

    NASA Technical Reports Server (NTRS)

    Davis, Sanford

    1991-01-01

    Report describes computations of unsteady facilitated transport of oxygen through liquid membrane of hemoglobin. Used here, "facilitated transport" means diffusion of permeant through membrane in which that diffusion enhanced by reversible chemical reaction between permeant and membrane. In this case, reversible reactions between hemoglobin and oxygen.

  5. Altered Response to Neuroendocrine Challenge Linked to Indices of the Metabolic Syndrome in Healthy Adults

    PubMed Central

    Tyrka, A. R.; Walters, O. C.; Price, L. H.; Anderson, G. M.; Carpenter, L. L.

    2013-01-01

    Metabolic syndrome (MetS) is characterized by central obesity, hypertension, insulin resistance, and hypercholesterolemia. Hypothalamic-pituitary-adrenal (HPA) axis activity is frequently abnormal in MetS, and excessive cortisol exposure may be implicated in metabolic derangements. We investigated the hypothesis that cortisol and adrenocorticotropic hormone (ACTH) responses to a standardized neuroendocrine challenge test would be associated with indices of MetS in a community sample of healthy adults. Healthy adults, 125 men and 170 women, without significant medical problems or chronic medications were recruited from the community. Participants completed the dexamethasone/corticotropin-releasing hormone (Dex/CRH) test, and anthropometric measurements, blood pressure, glycosylated hemoglobin (HbA1c), and cholesterol were measured. Participants reported on their history of early life stress and recent stress, as well as mood and anxiety symptoms. Cortisol and ACTH responses to the Dex/CRH test were negatively associated with measures of central adiposity (p < 0.001) and blood pressure (p < 0.01), and positively associated with HDL cholesterol (p < 0.01). These findings remained significant after controlling for body mass index (BMI). Measures of stress and anxiety and depressive symptoms were negatively correlated with cortisol and ACTH responses in the Dex/CRH test but were not related to MetS indices. That altered HPA axis function is linked to MetS components even in a healthy community sample suggests that these processes may be involved in the pathogenesis of MetS. Identification of premorbid risk processes might allow for detection and intervention prior to the development of disease. PMID:22549400

  6. [Spectroscopic studies of guanidine hydrochloride-induced unfolding of hemoglobin].

    PubMed

    Li, Jin-Jing; Tang, Qian; Cao, Hong-Yu; Zhang, Yu-Jiao; Zhang, Tao; Zheng, Xue-Fang

    2012-09-01

    In the present paper, based on the ultraviolet-visible (UV-Vis) absorption spectroscopy, fluorescence spectroscopy, and stopped flow-fluorescence spectroscopy, the authors studied the protein unfolding process of hemoglobin induced by GdmHcl. The experiments result shows that there were two different procedures about GdmHcl inducing hemoglobin unfolding from the evidences of UV-Vis absorption spectrum and fluorescence phase diagrams. Namely, the hemoglobin subunit exhibits depolymerization, forming the intermediates when incubated with GdmHcl at the concentration of 1. 0 mol x L(-1). With the increase in the concentration, various subunit structure became loose gradually, and the protoheme collapsed eventually. UV-Vis absorption spectroscopy indicates that the addition of reductant can cooperate with the depolymerization of hemoglobin subunit and the disaggregation of protoheme. The reductant results in the unfolding procedure that hemoglobin from "three-state model" turns into "two-state model".

  7. Hemoglobin values: comparative survey of the 1976 Canadian Olympic team.

    PubMed Central

    Clement, D. B.; Asmundson, R. C.; Medhurst, C. W.

    1977-01-01

    In view of the role of hemoglobin in oxygen transport, the hemoglobin concentration in whole blood may indicate readiness for maximal physical performance. Hemoglobin concentrations were determined in members of the 1976 Canadian Olympic team and compared with those of the 1975 Canadian general population and with published data for the 1968 Australian and Dutch Olympic teams. The mean hemoglobin concentrations of the 123 male and 64 female Canadian Olympic athletes were 14.7 +/- 1.0 and 12.9 +/- 0.7 g/dL, respectively. Both male and female Canadian Olympic athletes had significantly lower (P less than 0.01) values than the other three groups. The suboptimal hemoglobin concentrations may be related to inadequate dietary intake of protein and iron. PMID:902207

  8. The effect of cationic starch on hemoglobin, and the primary attempt to encapsulate hemoglobin.

    PubMed

    Gao, Wei; Sha, Baoyong; Liu, Yongchun; Wu, Daocheng; Shen, Xin; Jing, Guixia

    2015-06-01

    Though starch has been a common material used for drug delivery, it has not been used as an encapsulation material for hemoglobin-based oxygen carriers. In this study, cationic amylose (CA) was synthesized by an etherification reaction. The interaction behaviors between CA and hemoglobin (Hb) were measured by zeta potential, size, and UV-Vis absorption spectra at different pH values. Cationic starch encapsulated Hb by electrostatic adhesion, reverse micelles, and cross-linking, and showed a core shell structure with a size of around 100 nm, when measured immediately after dispersing in PBS solution. However, we found that it was prone to swell, aggregate, and leak Hb with a longer duration of dispersal in PBS.

  9. Managing type 2 diabetes: balancing HbA1c and body weight.

    PubMed

    Mavian, Annie A; Miller, Stephan; Henry, Robert R

    2010-05-01

    Most patients with type 2 diabetes present with comorbid overweight or obesity. Reaching and maintaining acceptable glycemic control is more difficult in overweight and obese patients, and these conditions are associated with increased risk for cardiovascular and other diseases. Glycemic management for these patients is complicated by the fact that insulin and many of the oral medications available to treat type 2 diabetes produce additional weight gain. However, an increasing number of therapeutic options are available that are weight neutral or lead to weight loss in addition to their glycemic benefits. This article evaluates the evidence from clinical trials regarding the relative glycemic benefits, measured in terms of glycated hemoglobin change, versus the impact on body weight of each medication currently approved for type 2 diabetes. In general, the sulfonylureas, thiazolidinediones, and D-phenylalanine derivatives have been shown to promote weight gain. The dipeptidyl peptidase-4 inhibitors are weight neutral, while the biguanides, incretin mimetics, and amylin mimetics promote weight loss. Trials examining the glycemic benefits of the weight loss agents orlistat and sibutramine are also examined. Awareness of this evidence base can be used to inform medication selection in support of weight management goals for patients with type 2 diabetes.

  10. Bohr effect of hemoglobins: Accounting for differences in magnitude.

    PubMed

    Okonjo, Kehinde O

    2015-09-07

    The basis of the difference in the Bohr effect of various hemoglobins has remained enigmatic for decades. Fourteen amino acid residues, identical in pairs and located at specific 'Bohr group positions' in human hemoglobin, are implicated in the Bohr effect. All 14 are present in mouse, 11 in dog, eight in pigeon and 13 in guinea pig hemoglobin. The Bohr data for human and mouse hemoglobin are identical: the 14 Bohr groups appear at identical positions in both molecules. The dog data are different from the human because three Bohr group positions are occupied by non-ionizable groups in dog hemoglobin; the pigeon data are vastly different from the human because six Bohr group positions are occupied by non-ionizable groups in pigeon hemoglobin. The guinea pig data are quite complex. Quantitative analyses showed that only the pigeon data could be fitted with the Wyman equation for the Bohr effect. We demonstrate that, apart from guinea pig hemoglobin, the difference between the Bohr effect of each of the other hemoglobins and of pigeon hemoglobin can be accounted for quantitatively on the basis of the occupation of some of their Bohr group positions by non-ionizable groups in pigeon hemoglobin. We attribute the anomalous guinea pig result to a new salt-bridge formed in its R2 quaternary structure between the terminal NH3(+) group of one β-chain and the COO(-) terminal group of the partner β-chain in the same molecule. The pKas of this NH3(+) group are 6.33 in the R2 and 4.59 in the T state.

  11. Propofol Enhances Hemoglobin-Induced Cytotoxicity in Neurons

    PubMed Central

    Yuan, Jing; Cui, Guiyun; Li, Wenlu; Zhang, Xiaoli; Wang, Xiaoying; Zheng, Hui; Zhang, Jian; Xiang, Shuanglin; Xie, Zhongcong

    2016-01-01

    BACKGROUND It has been increasingly suggested that propofol protects against hypoxic-/ischemic-induced neuronal injury. As evidenced by hemorrhage-induced stroke, hemorrhage into the brain may also cause brain damage. Whether propofol protects against hemorrhage-induced brain damage remains unknown. Therefore, in this study, we investigated the effects of propofol on hemoglobin-induced cytotoxicity in cultured mouse cortical neurons. METHODS Neurons were prepared from the cortex of embryonic 15-day-old mice. Hemoglobin was used to induce cytotoxicity in the neurons. The neurons were then treated with propofol for 4 hours. Cytotoxicity was determined by lactate dehydrogenase release assay. Caspase-3 activation was examined by Western blot analysis. Finally, the free radical scavenger U83836E was used to examine the potential involvement of oxidative stress in propofol’s effects on hemoglobin-induced cytotoxicity. RESULTS We found that treatment with hemoglobin induced cytotoxicity in the neurons. Propofol enhanced hemoglobin-induced cytotoxicity. Specifically, there was a significant difference in the amount of lactate dehydrogenase release between hemoglobin plus saline (19.84% ± 5.38%) and hemoglobin plus propofol (35.79% ± 4.41%) in mouse cortical neurons (P = 0.00058, Wilcoxon Mann-Whitney U test, n = 8 in the control group or the treatment group). U83836E did not attenuate the enhancing effects of propofol on hemoglobin-induced cytotoxicity in the neurons, and propofol did not significantly affect caspase-3 activation induced by hemoglobin. These data suggested that caspase-3 activation and oxidative stress might not be the underlying mechanisms by which propofol enhanced hemoglobin-induced cytotoxicity. Moreover, these data suggested that the neuroprotective effects of propofol would be dependent on the condition of the brain injury, which will need to be confirmed in future studies. CONCLUSIONS These results from our current proof-of-concept study should

  12. Noninvasive measurement of cerebral hemoglobin oxygen saturation using two near infrared spectroscopy approaches.

    PubMed

    Quaresima, V; Sacco, S; Totaro, R; Ferrari, M

    2000-04-01

    Spatially resolved spectroscopy (SRS) is a new near infrared spectroscopy (NIRS) method that, using the multi-distance approach, measures local cerebral cortex hemoglobin oxygen saturation [J. Matcher, P. Kirkpatrick, K. Nahid, M. Cope, and D. T. Delpy, Proc. SPIE 2389, 486-495 (1995)]. Using a conventional continuous wave NIRS photometer, cerebral venous oxygen saturation (SvO2) can be calculated from oxyhemoglobin and total hemoglobin rise induced by partial occlusion of jugular vein [C. E. Elwell, S. J. Matcher, L. Tyszczuk, J. H. Meek, and D. T. Delpy, Adv. Exp. Med. Biol. 411, 453-460 (1997)]. The aim of this study was to compare direct measurements of forehead tissue oxygenation index (TOI) with the calculated SvO2 during venous occlusion in 16 adult volunteers using a clinical two-channel SRS oximeter (NIRO-300). Measured TOI and calculated SvO2 values of either right or left forehead did not significantly differ. A good agreement between the two NIRS methods was also demonstrated. On 16 other subjects, no significant differences were found between the right and left forehead TOI values measured simultaneously, and between the TOI values measured by channel 1 or 2 on the same side. The results confirm that cerebral cortex hemoglobin oxygen saturation, measured directly by the SRS method, reflects predominantly the saturation of the intracranial venous compartment of circulation.

  13. Erythrocyte Enrichment in Hematopoietic Progenitor Cell Cultures Based on Magnetic Susceptibility of the Hemoglobin

    PubMed Central

    Jin, Xiaoxia; Abbot, Stewart; Zhang, Xiaokui; Kang, Lin; Voskinarian-Berse, Vanessa; Zhao, Rui; Kameneva, Marina V.; Moore, Lee R.; Chalmers, Jeffrey J.; Zborowski, Maciej

    2012-01-01

    Using novel media formulations, it has been demonstrated that human placenta and umbilical cord blood-derived CD34+ cells can be expanded and differentiated into erythroid cells with high efficiency. However, obtaining mature and functional erythrocytes from the immature cell cultures with high purity and in an efficient manner remains a significant challenge. A distinguishing feature of a reticulocyte and maturing erythrocyte is the increasing concentration of hemoglobin and decreasing cell volume that results in increased cell magnetophoretic mobility (MM) when exposed to high magnetic fields and gradients, under anoxic conditions. Taking advantage of these initial observations, we studied a noninvasive (label-free) magnetic separation and analysis process to enrich and identify cultured functional erythrocytes. In addition to the magnetic cell separation and cell motion analysis in the magnetic field, the cell cultures were characterized for cell sedimentation rate, cell volume distributions using differential interference microscopy, immunophenotyping (glycophorin A), hemoglobin concentration and shear-induced deformability (elongation index, EI, by ektacytometry) to test for mature erythrocyte attributes. A commercial, packed column high-gradient magnetic separator (HGMS) was used for magnetic separation. The magnetically enriched fraction comprised 80% of the maturing cells (predominantly reticulocytes) that showed near 70% overlap of EI with the reference cord blood-derived RBC and over 50% overlap with the adult donor RBCs. The results demonstrate feasibility of label-free magnetic enrichment of erythrocyte fraction of CD34+ progenitor-derived cultures based on the presence of paramagnetic hemoglobin in the maturing erythrocytes. PMID:22952572

  14. Erythrocyte enrichment in hematopoietic progenitor cell cultures based on magnetic susceptibility of the hemoglobin.

    PubMed

    Jin, Xiaoxia; Abbot, Stewart; Zhang, Xiaokui; Kang, Lin; Voskinarian-Berse, Vanessa; Zhao, Rui; Kameneva, Marina V; Moore, Lee R; Chalmers, Jeffrey J; Zborowski, Maciej

    2012-01-01

    Using novel media formulations, it has been demonstrated that human placenta and umbilical cord blood-derived CD34+ cells can be expanded and differentiated into erythroid cells with high efficiency. However, obtaining mature and functional erythrocytes from the immature cell cultures with high purity and in an efficient manner remains a significant challenge. A distinguishing feature of a reticulocyte and maturing erythrocyte is the increasing concentration of hemoglobin and decreasing cell volume that results in increased cell magnetophoretic mobility (MM) when exposed to high magnetic fields and gradients, under anoxic conditions. Taking advantage of these initial observations, we studied a noninvasive (label-free) magnetic separation and analysis process to enrich and identify cultured functional erythrocytes. In addition to the magnetic cell separation and cell motion analysis in the magnetic field, the cell cultures were characterized for cell sedimentation rate, cell volume distributions using differential interference microscopy, immunophenotyping (glycophorin A), hemoglobin concentration and shear-induced deformability (elongation index, EI, by ektacytometry) to test for mature erythrocyte attributes. A commercial, packed column high-gradient magnetic separator (HGMS) was used for magnetic separation. The magnetically enriched fraction comprised 80% of the maturing cells (predominantly reticulocytes) that showed near 70% overlap of EI with the reference cord blood-derived RBC and over 50% overlap with the adult donor RBCs. The results demonstrate feasibility of label-free magnetic enrichment of erythrocyte fraction of CD34+ progenitor-derived cultures based on the presence of paramagnetic hemoglobin in the maturing erythrocytes.

  15. Does Iron Deficiency Anaemia and its Severity Influence HbA1C Level in Non Diabetics? An Analysis of 150 Cases

    PubMed Central

    Ganapathy, Shivashekar; Arunachalam, Sundaram; Raja, Veena; Ramraj, Balaji

    2017-01-01

    Introduction Anaemia has a high prevalence having great impact worldwide and potentially contributing to the pathogenesis of various chronic diseases. Approximately 1/3rd of patients with anaemia have iron deficiency. American Diabetes Association (ADA) has affirmed Glycated Haemoglobin (HbA1C) ≥ 6.5% as a diagnostic criterion for Diabetes Mellitus (DM). Variation of HbA1C in Iron Deficiency Anaemia (IDA) has clashing results. Aim To decide the impact of IDA on HbA1C levels among non diabetics. To assess and analyse the variation of HbA1C according to the degree of anaemia (mild, moderate and severe). Materials and Methods This cross-sectional study was carried out in SRM Medical College Hospital and Research Centre, Chennai, Tamil Nadu from February 2016 to October 2016 and approved by our Institutional Ethical Committee. Totally 150 non diabetics (75 with IDA and 75 without IDA) were included in this study. Medical history was recorded and HbA1C, Haemoglobin (Hb), Haematocrit (Hct), red cell indices, serum iron, ferritin and Fasting Plasma Glucose (FPG) were tested. Results The IDA patients in this study had a mean HbA1C (6.84±0.07%) which was higher than the non anaemic group (5.12±0.04%) and this difference was statistically significant (p< 0.05). HbA1C level was increased when severity of anaemia worsened. Also, noteworthy statistical significance was observed between no anaemia, mild, moderate and severe anaemia (p< 0.05). Conclusion In this study, we observed a positive correlation between IDA and elevated HbA1C level in non-diabetic population.

  16. Altered Concentrations of Copper, Zinc, and Iron are Associated With Increased Levels of Glycated Hemoglobin in Patients With Type 2 Diabetes Mellitus and Their First-Degree Relatives

    PubMed Central

    Atari-Hajipirloo, Somayeh; Valizadeh, Neda; Khadem-Ansari, Mohammad-Hassan; Rasmi, Yousef; Kheradmand, Fatemeh

    2016-01-01

    Background The altered levels of some essential trace elements and antioxidant minerals have been observed in diabetic patients. Objectives The aim of the present study was to compare the concentrations of essential trace elements, copper (Cu), zinc (Zn), and iron (Fe) in the serum of patients who have type 2 diabetes mellitus (T2DM) with those of their non-diabetic first-degree relatives (FDR) and control subjects. The association between glycated hemoglobin (HbA1c) and levels of metals was also evaluated. Patients and Methods We studied 46 subjects with T2DM, 46 FDR, and 50 control subjects matched for age and sex. Serum concentrations of Cu, Zn, and Fe were measured by colorimetric kit. Fasting blood glucose (FBG) and HbA1c were assayed using the standard kit. Results An imbalance in the levels of the studied metals was observed in both patients with T2DM and FDR. We found significantly decreased levels of Zn and higher levels of Cu and Fe in the patients with T2DM and FDR when compared with the control subjects (P < 0.05). HbA1c levels were positively correlated with Cu and Fe and inversely correlated with Zn in the patients with T2DM and FDR (P < 0.05). Conclusions The patients with T2DM and FDR had altered contents of Cu, Zn, and Fe that might be a predisposing factor to the development of diabetes in future or vice versa the result of diabetes development. Impaired metabolism of these elements may contribute to the augmented risk of developing type 2 diabetes mellitus later in the life of their first-degree relatives. PMID:27761143

  17. Combined use of fasting plasma glucose and glycated hemoglobin A1c in a stepwise fashion to detect undiagnosed diabetes mellitus.

    PubMed

    Nakagami, Tomoko; Tominaga, Makoto; Nishimura, Rimei; Daimon, Makoto; Oizumi, Toshihide; Yoshiike, Nobuo; Tajima, Naoko

    2007-09-01

    Type 2 diabetes mellitus (DM) is a common and serious condition related with considerable morbidity. Screening for DM is one strategy for reducing this burden. In Japan National Diabetes Screening Program (JNDSP) guideline, the combined use of fasting plasma glucose (FPG) and glycated hemoglobin A1c (HbA1c) in a stepwise fashion has been recommended to identify the group of people needing life-style counseling or medical care. However, the efficacy of this program has not been fully evaluated, as an oral glucose tolerance test (OGTT) is not mandatory in the guideline. The aim of this study was to assess the validity of the screening test scenario, in which an OGTT would be applied to people needing life-style counseling or medical care on this guideline: FPG 110-125 mg/dl and HbA1c over 5.5%. Subjects were 1,726 inhabitants without a previous history of DM in the Funagata study, which is a population-based survey conducted in Yamagata prefecture to clarify the risk factors, related conditions, and consequences of DM. DM was diagnosed according to the 1999 World Health Organization criteria. The prevalence of undiagnosed DM was 6.6%. The tested screening scenario gave a sensitivity of 55.3%, a specificity of 98.4%, a positive predictive value of 70.8%, and a negative predictive value of 96.9% for undiagnosed DM. In conclusion, the screening test scenario, in which an OGTT would be followed by the combined use of FPG and HbA1c in a stepwise fashion according to the JNDSP guideline, was not effective in identifying people with undiagnosed DM.

  18. Familial secondary erythrocytosis due to increased oxygen affinity is caused by destabilization of the T state of hemoglobin Brigham (α2β2Pro100Leu)

    PubMed Central

    Mollan, Todd L; Abraham, Bindu; Strader, Michael Brad; Jia, Yiping; Lozier, Jay N; Olson, John S; Alayash, Abdu I

    2012-01-01

    Hemoglobin Brigham (β Pro100 to Leu) was first reported in a patient with familial erythrocytosis. Erythrocytes of an affected individual from the same family contain both HbA and Hb Brigham and exhibit elevated O2 affinity compared with normal cells (P50 = 23 mm Hg vs. 31 mmHg at pH 7.4 at 37°C). O2 affinities measured for hemolysates were sensitive to changes in pH or chloride concentrations, indicating little change in the Bohr and Chloride effects. Hb Brigham was separated from normal HbA by nondenaturing cation exchange liquid chromatography, and the amino acid substitution was verified by mass spectrometry. The properties of Hb Brigham isolated from the patient's blood were then compared with those of recombinant Hb Brigham expressed in Escherichia coli. Kinetic experiments suggest that the rate constants for ligand binding and release in the high (R) and low (T) affinity quaternary states of Hb Brigham are similar to those of native hemoglobin. However, the Brigham mutation decreases the T to R equilibrium constant (L) which accelerates the switch to the R state during ligand binding to deoxy-Hb, increasing the rate of association by approximately twofold, and decelerates the switch during ligand dissociation from HbO2, decreasing the rate approximately twofold. These kinetic data help explain the high O2 affinity characteristics of Hb Brigham and provide further evidence for the importance of the contribution of Pro100 to intersubunit contacts and stabilization of the T quaternary structure. PMID:22821886

  19. New analytical tools and epidemiological data for the identification of HbA2 borderline subjects in the screening for beta-thalassemia.

    PubMed

    Mosca, Andrea; Paleari, Renata; Galanello, Renzo; Sollaino, Carla; Perseu, Lucia; Demartis, Franca Rosa; Passarello, Cristina; Giambona, Antonino; Maggio, Aurelio

    2008-08-01

    The increase of HbA(2) is the most important feature in the identification of beta-thalassemia carriers. However, some carriers are difficult to identify, because the level of HbA(2) is not in the typical range. Few data are available concerning the prevalence of such unusual phenotypes, and knowing their expected prevalence could be helpful in detecting systematic drifts in the analytical systems for HbA(2) quantification. In this study we report a retrospective investigation in two centres with high prevalence of beta-thalassemia. The prevalence of borderline subjects was found to be 2.2 and 3.0%, respectively. The genotypes of a subgroup of these subjects were then analyzed and in about 25% of cases a mutation in the globin genes was identified. We conclude that the occurrence of HbA(2) borderline phenotypes is not a rare event. In order to obtain more accurate HbA(2) measurements the development of an international reference measurement system for HbA(2), based on quantitative peptide mapping, has been recently started. We believe that the innovative approach of our method could also be used as a model to develop accurate quantitative methods for other red cell proteins relevant to the biodynamic properties and the surface electrochemistry of erythrocytes.

  20. Reduced Histone H3 Lysine 9 Methylation Contributes to the Pathogenesis of Latent Autoimmune Diabetes in Adults via Regulation of SUV39H2 and KDM4C

    PubMed Central

    Liu, Xi-yu

    2017-01-01

    Aims. Latent autoimmune diabetes in adults (LADA) is an autoimmune disease of which the mechanism is not clear. Emerging evidence suggests that histone methylation contributes to autoimmunity. Methods. Blood CD4+ T lymphocytes from 26 LADA patients and 26 healthy controls were isolated to detect histone H3 lysine 4 and H3 lysine 9 methylation status. Results. Reduced global H3 lysine 9 methylation was observed in LADA patients' CD4+ T lymphocytes, compared to healthy controls (P < 0.05). H3 lysine 4 methylation was not statistically different. The reduced H3 lysine 9 methylation was associated with GADA titer but not correlated with glycosylated hemoglobin (HbA1c). When the LADA patient group was divided into those with complication and those without, relatively reduced global H3 lysine 9 methylation was observed in LADA patients with complication (P < 0.05). The expression of histone methyltransferase SUV39H2 for H3 lysine 9 methylation was downregulated in LADA patients, and the expression of histone demethylase KDM4C which made H3 lysine 9 demethylation was upregulated. Conclusion. The reduction of histone H3 lysine 9 methylation which may due to the downregulation of methyltransferase SUV39H2 and the upregulation of demethylase KDM4C was found in CD4+ T lymphocytes of LADA patients.

  1. Prognostic value of glycated hemoglobin in colorectal cancer

    PubMed Central

    Ferroni, Patrizia; Formica, Vincenzo; Della-Morte, David; Lucchetti, Jessica; Spila, Antonella; D'Alessandro, Roberta; Riondino, Silvia; Guadagni, Fiorella; Roselli, Mario

    2016-01-01

    AIM To investigate the clinical significance of routinely used glycemic parameters in a cohort of colorectal cancer (CRC) patients. METHODS Pre-treatment fasting blood glucose, insulin, HbA1c and homeostasis model of risk assessment (HOMA-IR) were retrospectively evaluated in a case-control study of 224 CRC and 112 control subjects matched for sex, obesity and diabetes frequency and blood lipid profile. Furthermore, the prognostic value of routinely used glycemic parameters towards progression-free (PFS) and overall survival (OS) was prospectively evaluated. RESULTS Fasting blood glucose, insulin, HOMA-IR and HbA1c (all P < 0.0001) levels were higher in non-diabetic CRC patients compared with obesity-matched controls. All parameters were associated with increased CRC risk at ROC analysis, but no relationship with clinical-pathological variables or survival outcomes was observed for glycemia, insulinemia or HOMA-IR. Conversely, advanced CRC stage (P = 0.018) was an independent predictor of increased HbA1c levels, which were also higher in patients who had disease progression compared with those who did not (P = 0.05). Elevated HbA1c levels showed a negative prognostic value both in terms of PFS (HR = 1.24) and OS (HR = 1.36) after adjustment for major confounders, which was further confirmed in a subgroup analysis performed after exclusion of diabetic patients. CONCLUSION HbA1c might have a negative prognostic value in CRC, thus suggesting that glycemic metabolic markers should be carefully monitored in these patients, independently of overt diabetes. PMID:28018105

  2. The primary structure of genetic variants of mouse hemoglobin

    SciTech Connect

    Popp, R.A.; Bailiff, E.G.; Skow, L.C.; Whitney, J.B. III

    1982-01-01

    The primary structures of the ..cap alpha.. globins from CE/J, DBA/2J, and a stock of Potter's mice were determined to identify the amino acid substitutions associated with the unique isoelectric focusing patterns of these hemoglobins. In addition, the primary structures of the ..cap alpha.. globins from MOL III and PERU mice were studied in search of amino acid substitutions that may not be detected by isoelectric focusing. CE/J hemoglobin contains a unique kind of ..cap alpha.. globin called chain 5. It differs from the single kind of ..cap alpha.. globin (chain 1) in C57BL/6 by having alanine rather than glycine at position 78. DBA/2J hemoglobin has two kinds of ..cap alpha.. globins: one half is like chain 5 and the other half is like chain 1. The hemoglobin from Potter's stock of Mus musculus molossinus also contains chains 1 and 5, but they are expressed at different levels (i.e., 80% chain 1 and 20% chain 5). MOL III hemoglobin has a single kind of ..cap alpha.. globin identical to that in C57BL/6, and PERU hemoglobin contains approximately 40% chain 1 and 60% chain 4. Chains 1 and 4 have different amino acids at positions 25, 62, and 68. These studies confirm that mouse hemoglobins separable by isoelectric focusing, but not by other means of electrophoresis, have substitutions of neutrally charged amino acids in their ..cap alpha.. chains.

  3. Two-photon excited fluorescence emission from hemoglobin

    NASA Astrophysics Data System (ADS)

    Sun, Qiqi; Zeng, Yan; Zhang, Wei; Zheng, Wei; Luo, Yi; Qu, Jianan Y.

    2015-03-01

    Hemoglobin, one of the most important proteins in blood, is responsible for oxygen transportation in almost all vertebrates. Recently, we discovered two-photon excited hemoglobin fluorescence and achieved label-free microvascular imaging based on the hemoglobin fluorescence. However, the mechanism of its fluorescence emission still remains unknown. In this work, we studied the two-photon excited fluorescence properties of the hemoglobin subunits, heme/hemin (iron (II)/(III) protoporphyrin IX) and globin. We first studied the properties of heme and the similar spectral and temporal characteristics of heme and hemoglobin fluorescence provide strong evidence that heme is the fluorophore in hemoglobin. Then we studied the fluorescence properties of hemin, globin and methemoglobin, and found that the hemin may have the main effect on the methemoglobin fluorescence and that globin has tryptophan fluorescence like other proteins. Finally, since heme is a centrosymmetric molecule, that the Soret band fluorescence of heme and hemoglobin was not observed in the single photon process in the previous study may be due to the parity selection rule. The discovery of heme two-photon excited fluorescence may open a new window for heme biology research, since heme as a cofactor of hemoprotein has many functions, including chemical catalysis, electron transfer and diatomic gases transportation.

  4. Site-specific PEGylation of hemoglobin at Cys-93(beta): correlation between the colligative properties of the PEGylated protein and the length of the conjugated PEG chain.

    PubMed

    Manjula, B N; Tsai, A; Upadhya, R; Perumalsamy, K; Smith, P K; Malavalli, A; Vandegriff, K; Winslow, R M; Intaglietta, M; Prabhakaran, M; Friedman, J M; Acharya, A S

    2003-01-01

    Increasing the molecular size of acellular hemoglobin (Hb) has been proposed as an approach to reduce its undesirable vasoactive properties. The finding that bovine Hb surface decorated with about 10 copies of PEG5K per tetramer is vasoactive provides support for this concept. The PEGylated bovine Hb has a strikingly larger molecular radius than HbA (1). The colligative properties of the PEGylated bovine Hb are distinct from those of HbA and even polymerized Hb, suggesting a role for the colligative properties of PEGylated Hb in neutralizing the vasoactivity of acellular Hb. To correlate the colligative properties of surface-decorated Hb with the mass of the PEG attached and also its vasoactivity, we have developed a new maleimide-based protocol for the site-specific conjugation of PEG to Hb, taking advantage of the unusually high reactivity of Cys-93(beta) of oxy HbA and the high reactivity of the maleimide to protein thiols. PEG chains of 5, 10, and 20 kDa have been functionalized at one of their hydroxyl groups with a maleidophenyl moiety through a carbamate linkage and used to conjugate the PEG chains at the beta-93 Cys of HbA to generate PEGylated Hbs carrying two copies of PEG (of varying chain length) per tetramer. Homogeneous preparations of (SP-PEG5K)(2)-HbA, (SP-PEG10K)(2)-HbA, and (SP-PEG20K)(2)-HbA have been isolated by ion exchange chromatography. The oxygen affinity of Hb is increased slightly on PEGylation, but the length of the PEG-chain had very little additional influence on the O(2) affinity. Both the hydrodynamic volume and the molecular radius of the Hb increased on surface decoration with PEG and exhibited a linear correlation with the mass of the PEG chain attached. On the other hand, both the viscosity and the colloidal osmotic pressure (COP) of the PEGylated Hbs exhibited an exponential increase with the increase in PEG chain length. In contrast to the molecular volume, viscosity, and COP, the vasoactivity of the PEGylated Hbs was not a

  5. Prevalence and Risk Factors of Elevated Blood Pressure, Overweight, and Dyslipidemia in Adolescent and Young Adults in Rural Nepal

    PubMed Central

    Stewart, Christine P.; Wu, Lee S.F.; LeClerq, Steven C.; Khatry, Subarna K.; West, Keith P.

    2013-01-01

    Abstract Background Chronic disease begins early in life, yet population data are sparse on potential causal factors in children and young adults in South Asia. Methods We assessed risk factors for chronic disease in two population cohorts, aged 9–23 years, in rural Nepal. Assessed variables included short height (less than −2 z), high body mass index (BMI) (z>0.42), waist circumference (WC) >90 cm (male) or 80 cm (female) or age-adjusted child cutoff], high blood pressure (>120/80 mmHg), fasting glucose (≥100 mg/dL), glycosylated hemoglobin (HbA1c) (>7%), blood lipids [triglyceride, high-density lipoprotein cholesterol (HDL-C), and total cholesterol], diet, smoking, alcohol, and socioeconomic status (SES) factors. Results The population was stunted (46%) and few were overweight (∼2%–4% with high BMI or WC). Twelve percent had high blood pressure. Plasma hypertriglyceridemia (≥150 mg/dL) affected ∼8.5%, and 78% had low HDL-C concentrations <40 mg/dL (male) or <50 mg/dL (female)], while few (≤3%) had elevated total cholesterol (≥180 mg/dL), glucose, and HbA1c. Females were at higher risk than males for high blood pressure [odds ratio (OR) 1.9; 95% confidence interval (CI) 1.6–2.3] and overweight (4.2; 3.0–5.8), but had lower risk of dyslipidemia (0.7; 0.6–0.9). Ethnic plains Madheshi were less likely to be overweight (0.3; 0.2–0.4), but had greater risk of dyslipidemia (1.4; 1.1–1.7) versus those of Hill origin. Some dietary factors were significantly associated with high blood pressure or dyslipidemia, but not overweight. Conclusions Dyslipidemia and high blood pressure are emerging health concerns among young adults in rural Nepal. PMID:23682595

  6. Development of an immunoassay to detect benzene adducts in hemoglobin

    SciTech Connect

    Grassman, J.A.

    1993-01-01

    The purpose of this project was to develop an immunoassay to detect the adducts formed in hemoglobin after exposure to benzene, which is known to cause bone marrow degeneration and acute myelogenous leukemia. The use of benzene-adduct detection as a biological monitoring method would permit measurement of low exposures and exposures sustained weeks earlier. The reactivity of hydroquinone, an important benzene metabolite, with blood proteins and amino acids was investigated in order to decide which antigens and analytes were likely to be suitable for immunoassay development. The second section determined the combination of benzene-metabolite and antigen need to produce an immunoassay with the requisite low detection limit and specificity. The immunoassays with the best performance were tested on hemoglobin from benzene-exposed mice. In vitro studies showed that hydroquinone efficiently formed adducts with erythrocyte membranes and hemoglobin but not with albumin. Adduction efficiency was greater in incubations using purified hemoglobin than whole blood. Cysteine accounted for 15 to 27% of the adducts formed by hydroquinone. The site of the other adducts were not identified although there was evidence that the hemoglobin heme was adducted. Adducts were found on only 1 of the 2 globin chains. Tryptic digestion of the globin failed to associate the adducts with a specific peptide. Antigens made from hydroquinone-adducted hemoglobin but not hydroquinone-adducted cysteines coupled to carrier proteins effectively elicited adduct-specific antibodies. Interference due to reactivity to hemoglobin was controlled by using uniform quantities of hemoglobin in all wells. The mid-range of the best assays were approximately 12 pmoles HQ per well. Antibodies directed toward hemoglobin adducted with the benzene metabolites phenol, catechol and 1,2,4-trihydroxybenzene were also made. The performance of the anti-1,2,4-trihydroxybenzene were suitable for quantitative immunoassays.

  7. HCHL expression in hairy roots of Beta vulgaris yields a high accumulation of p-hydroxybenzoic acid (pHBA) glucose ester, and linkage of pHBA into cell walls.

    PubMed

    Rahman, Laiq ur; Kouno, Hitomi; Hashiguchi, Yuya; Yamamoto, Hirobumi; Narbad, Arjan; Parr, Adrian; Walton, Nicholas; Ikenaga, Toshihiko; Kitamura, Yoshie

    2009-10-01

    As part of a study to explore the potential for new or modified bio-product formation, Beta vulgaris (sugar beet) has been genetically modified to express in root-organ culture a bacterial gene of phenylpropanoid catabolism. The HCHL gene, encoding p-hydroxycinnamoyl-CoA hydratase/lyase, was introduced into B. vulgaris under the control of a CaMV 35S promoter, using Agrobacterium rhizogenes LBA 9402. Hairy root clones expressing the HCHL gene, together with non-expressing clones, were analysed and revealed that one expression-positive clone accumulated the glucose ester of p-hydroxybenzoic acid (pHBA) at about 14% on a dry weight basis. This is the best yield achieved in plant systems so far. Determination of cell-wall components liberated by alkaline hydrolysis confirmed that the ratio of pHBA to ferulic acid was considerably higher in the HCHL-expressing clones, whereas only ferulic acid was detected in a non-expressing clone. The change in cell-wall components also resulted in a decrease in tensile strength in the HCHL-expressing clones.

  8. [Hemoglobin O Arab in Ivory Coast and western Africa].

    PubMed

    Sangare, A; Sanogo, I; Meite, M; Ambofo, Y; Abesopie, V; Segbena, A; Tolo, A

    1992-01-01

    The authors report 44 cases of hemoglobin O Arab share out in 3 phenotypes (A O Arab, C O Arab and S O Arab). The study of this abnormal hemoglobin has allowed the following conclusions: The Hb O Arab is a rare mutant of hemoglobin. The heterozygote form A O Arab and the association Hb C--Hb O Arab do not present any clinical and hematological manifestations. The associations Hb S--Hb O Arab brings about a serious hemoglobinopathy which has clinical and hematological features like the sickle-cell disease (SSFA2).

  9. Hemoglobin function and allosteric regulation in semi-fossorial rodents (family Sciuridae) with different altitudinal ranges.

    PubMed

    Revsbech, Inge G; Tufts, Danielle M; Projecto-Garcia, Joana; Moriyama, Hideaki; Weber, Roy E; Storz, Jay F; Fago, Angela

    2013-11-15

    Semi-fossorial ground squirrels face challenges to respiratory gas transport associated with the chronic hypoxia and hypercapnia of underground burrows, and such challenges are compounded in species that are native to high altitude. During hibernation, such species must also contend with vicissitudes of blood gas concentrations and plasma pH caused by episodic breathing. Here, we report an analysis of hemoglobin (Hb) function in six species of marmotine ground squirrels with different altitudinal distributions. Regardless of their native altitude, all species have high Hb-O2 affinities, mainly due to suppressed sensitivities to allosteric effectors [2,3-diphosphoglycerate (DPG) and chloride ions]. This suppressed anion sensitivity is surprising given that all canonical anion-binding sites are conserved. Two sciurid species, the golden-mantled and thirteen-lined ground squirrel, have Hb-O2 affinities that are characterized by high pH sensitivity and low thermal sensitivity relative to the Hbs of humans and other mammals. The pronounced Bohr effect is surprising in light of highly unusual amino acid substitutions at the C-termini that are known to abolish the Bohr effect in human HbA. Taken together, the high O2 affinity of sciurid Hbs suggests an enhanced capacity for pulmonary O2 loading under hypoxic and hypercapnic conditions, while the large Bohr effect should help to ensure efficient O2 unloading in tissue capillaries. In spite of the relatively low thermal sensitivities of the sciurid Hbs, our results indicate that the effect of hypothermia on Hb oxygenation is the main factor contributing to the increased blood-O2 affinity in hibernating ground squirrels.

  10. Polychelated cryogels: hemoglobin adsorption from human blood.

    PubMed

    Erol, Kadir

    2017-02-01

    The separation and purification methods are extremely important for the hemoglobin (Hb) which is a crucial biomolecule. The adsorption technique is popular among these methods and the cryogels have been used quite much due to their macropores and interconnected flow channels. In this study, the Hb adsorption onto the Cu(II) immobilized poly(2-hydroxyethyl methacrylate-glycidyl methacrylate), poly(HEMA-GMA)-Cu(II), cryogels was investigated under different conditions (pH, interaction time, initial Hb concentration, temperature and ionic strength) to optimize adsorption conditions. The swelling test, Fourier transform infrared (FT-IR) spectroscopy, scanning electron microscope (SEM), surface area (BET), elemental and ICP-OES analysis were performed for the characterization of cryogels. Polyethyleneimine (PEI) molecule was used as a Cu(II)-chelating ligand. The Hb adsorption capacity of cryogels was determined as 193.8 mg Hb/g cryogel. The isolation of Hb from human blood was also studied under optimum adsorption conditions determined and the Hb (124.5 mg/g cryogel) was isolated. The adsorption model was investigated in the light of Langmuir and Freundlich adsorption isotherm models and it was determined to be more appropriate to the Langmuir adsorption isotherm model.

  11. Hyperspectral imaging for dermal hemoglobin spectroscopy

    NASA Astrophysics Data System (ADS)

    Dwyer, Peter J.; DiMarzio, Charles A.

    1999-10-01

    It has been shown previously that images collected at selected wavelengths in a sufficiently narrow bandwidth can be used to produce maps of the oxygen saturation of hemoglobin in the dermis. A four-wavelength algorithm has been developed based on a two-layer model of the skin, in which the blood is contained in the lower layer (dermis), while the upper layer attenuates some of the reflection and adds a clutter term. In the present work, the algorithm is compared analytically to simpler algorithms using three wavelengths and based on a single-layer model. It is shown through Monte-Carlo models that, for typical skin, the single-layer model is adequate to analyze data from fiber-optical reflectance spectroscopy, but the two-layer model produces better results for imaging systems. Although the model does not address the full complexity of reflectance of a two-layer skin, it has proven to be sufficient to recover the oxygen saturation, and perhaps other medically relevant information. The algorithm is demonstrated on a suction blister, where the epidermis is removed to reveal the underlying dermis. Applications for this imaging modality exist in dermatology, in surgery, and in developing treatment plans for various diseases.

  12. High-altitude adaptations in vertebrate hemoglobins.

    PubMed

    Weber, Roy E

    2007-09-30

    Vertebrates at high altitude are subjected to hypoxic conditions that challenge aerobic metabolism. O(2) transport from the respiratory surfaces to tissues requires matching between the O(2) loading and unloading tensions and the O(2)-affinity of blood, which is an integrated function of hemoglobin's intrinsic O(2)-affinity and its allosteric interaction with cellular effectors (organic phosphates, protons and chloride). Whereas short-term altitudinal adaptations predominantly involve adjustments in allosteric interactions, long-term, genetically-coded adaptations typically involve changes in the structure of the haemoglobin molecules. The latter commonly comprise substitutions of amino acid residues at the effector binding sites, the heme-protein contacts, or at intersubunit contacts that stabilize either the low-affinity ('Tense') or the high-affinity ('Relaxed') structures of the molecules. Molecular heterogeneity (multiple isoHbs with differentiated oxygenation properties) can further broaden the range of physico-chemical conditions where Hb functions under altitudinal hypoxia. This treatise reviews the molecular and cellular mechanisms that adapt haemoglobin-oxygen affinities in mammals, birds and ectothermic vertebrates at high altitude.

  13. MP4, a vasodilatory PEGylated hemoglobin.

    PubMed

    Cole, Russell H; Vandegriff, Kim D

    2011-01-01

    A vasodilatory hemoglobin (Hb)-based O(2) carrier (HBOC) has been developed by surface conjugation polyethylene glycol to tetrameric human Hb (MP4, Sangart, San Diego). Because the NO-binding kinetics of MP4 are similar to vasoconstrictive HBOCs, we propose that the decoupling of NO scavenging from vascular response is a consequence of MP4's high O(2) affinity (p50 = 5 mmHg) and unique surface chemistry. The release of ATP from erythrocytes is vasodilatory and the application of a high O(2) affinity HBOC minimizes ATP interference with intravascular ATP signaling. A second potential mechanism of action for MP4 involves the surface conjugation of polyethylene glycol (PEG) to tetrameric human Hb. It has been shown that the addition of unconjugated high molecular weight (Mw) PEG to cultured lung endothelial cells causes an immediate and significant reduction in endothelial permeability; an effect opposite to that of endothelial agonists such as cell-free Hb. It appears that some of the benefits of the PEG-endothelium interaction are carried onto molecules such as PEGylated Hb and PEGylated albumin, as demonstrated by favorable hemodynamic responses in vivo. PEGylation of ß93 cysteine residues, as in MP4, has also been reported to increase the nitrite reductase activity of Hb and enhance conversion of endogenous nitrite to bioactive NO.

  14. NITRO MUSK BOUND TO CARP HEMOGLOBIN ...

    EPA Pesticide Factsheets

    Nitroaromatic compounds including synthetic nitro musks are important raw materials and intermediates in the synthesis of explosives, dyes, and pesticides, pharmaceutical and personal care-products (PPCPs). The nitro musks such as musk xylene (MX) and musk ketone (MK) are extensively used as fragrance ingredients in PPCPs and other commercial toiletries. Identification and quantification of a bound 4-amino-MX (4-AMX) metabolite as well as a 2- amino-MK (2-AMK) metabolite were carried out by gas chromatography-mass spectrometry' (GC/MS), with selected ion monitoring (SIM) in both the electron ionization (ElMS) and electron capture (EC) negative ion chemical ionization (NICIMS) modes. Detection of 4-AMX and 2-AMK occurred after the cysteine adducts in carp hemoglobin, derived from the nitroso metabolites, were released by alkaline hydrolysis. The released metabolites were extracted into n-hexane. The extract was preconcentrated by evaporation, and analyzed by GC-SIM-MS. A comparison between the El and EC approaches was made. EC NICIMS detected both metabolites whereas only 4-AMX was detected by ElMS. The EC NICIMS approach exhibited fewer matrix responses and provided a lower detection limit. Quantitation in both approaches was based on internal standard and a calibration plot. The research focused on in the subtasks is the development and application of state-of the-art technologies to meet the needs of the public, Office of Water, and ORD in the area of Water Q

  15. Selenium binding to human hemoglobin via selenotrisulfide.

    PubMed

    Haratake, Mamoru; Fujimoto, Katsuyoshi; Ono, Masahiro; Nakayama, Morio

    2005-05-25

    Selenotrisulfide (e.g., glutathione selenotrisulfide (GSSeSG)) is an important intermediate in the metabolism of selenite. However, its reactivity with biological substances such as peptides and proteins in the subsequent metabolism is still far from clearly understood, because of its chemical instability under physiological conditions. Penicillamine (Pen) is capable of generating a chemically stable and isolatable selenotrisulfide, PenSSeSPen. To explore the metabolic fate of selenite in red blood cells (RBC), we investigated the reaction of selenotrisulfide with human hemoglobin (Hb) using PenSSeSPen as a model. PenSSeSPen rapidly reacted with Hb under physiological conditions. From the analysis of selenium binding using the Langmuir type binding equation, the apparent binding number of selenium per Hb tetramer almost corresponded to the number of reactive thiol groups of Hb. The thiol group blockade of Hb by iodoacetamide treatment completely inhibited the reaction of PenSSeSPen with Hb. In addition, MALDI-TOF mass spectrometric analysis of the selenium-bound Hb revealed that PenSSe moiety binds to the beta subunits of Hb. Overall, the reaction of PenSSeSPen with Hb appears to involve the thiol exchange between Pen and the cysteine residues on the beta subunit of Hb.

  16. [Age and sex variations of HbA(1C) in a French population without known diabetes aged 6 to 79 years].

    PubMed

    Gusto, Gaëlle; Vol, Sylviane; Born, Catherine; Balkau, Beverley; Lamy, Jocelyne; Bourderioux, Christiane; Lantieri, Olivier; Tichet, Jean

    2011-01-01

    HbA(1C) is being used for screening and diagnosing diabetes. We determined mean values of HbA(1C) according to age and sex in a large population without known diabetes, in a wide age range 6-79  years. 5,138 men and women without known diabetes aged 6-79  years participated in a routine health examination provided by their medical insurance. HbA(1C) was assessed on an HPLC analyzer aligned with a DCCT method. HbA(1C) was approximately normally distributed in both men and women. Mean (SD) HbA(1C) were, for men vs women, in percentages 5.3 (0.4) vs 5.2 (0.3), in mmol/mol 34 (5) vs 34 (4) and in estimated blood glucose in mmol/L 5.83 (0.67) vs 5.75 (0.53). HbA(1C) increased with age by 0.08% every 10  years and this was attenuated to a 0.04% increase after adjustment on fasting plasma glucose. Between 15 and 49  years, women had lower values than men (p < 0.0001), but no sex differences were observed before and after this age range. In our population, 0.6% had HbA(1C) greater or equal to 6.5% and 88% (96% of men and 73% of women) of them had fasting plasma glucose greater or equal to 6,1 mmol/L. Threshold of 6.0% selected 2.8% of our population.

  17. Coexpression of Human α- and Circularly Permuted β-Globins Yields a Hemoglobin with Normal R State but Modified T State Properties†

    PubMed Central

    Asmundson, Anna L.; Taber, Alexandria M.; van der Walde, Adella; Lin, Danielle H.; Olson, John S.; Anthony-Cahill, Spencer J.

    2009-01-01

    For the first time, a circularly permuted human β-globin (cpβ) has been coexpressed with human α-globin in bacterial cells and shown to associate to form α-cpβ hemoglobin in solution. Flash photolysis studies of α-cpβ show markedly biphasic CO and O2 kinetics with the amplitudes for the fast association phases being dominant due the presence of large amounts of high-affinity liganded hemoglobin dimers. Extensive dimerization of liganded but not deoxygenated α-cpβ was observed by gel chromatography. The rate constants for O2 and CO binding to the R state forms of α-cpβ are almost identical to those of native HbA (k′R(CO) ≈ 5.0 μM−1 s−1; k′R(O2) ≈ 50 μM−1 s−1), and the rate of O2 dissociation from fully oxygenated α-cpβ is also very similar to that observed for HbA (kR(O2) ≈ 21–28 s−1). When the equilibrium deoxyHb form of α-cpβ is reacted with CO in rapid mixing experiments, the observed time courses are monophasic and the observed bimolecular association rate constant is ∼1.0 μM−1 s−1, which is intermediate between the R state rate measured in partial photolysis experiments (∼5 μM−1 s−1) and that observed for T state deoxyHbA (k′T(CO) ≈ 0.1 to 0.2 μM−1 s−1). Thus the deoxygenated permutated β subunits generate an intermediate, higher affinity, deoxyHb quaternary state. This conclusion is supported by equilibrium oxygen binding measurements in which α-cpβ exhibits a P50 of ∼1.5 mmHg and a low n-value (∼1.3) at pH 7, 20 °C, compared to 8.5 mmHg and n ≈ 2.8 for native HbA under identical, dilute conditions. PMID:19397368

  18. Prevalence of β-Thalassemia and hemoglobin E in two migrant populations of Manipur, North East India.

    PubMed

    Achoubi, Nongthombam; Asghar, Mohammad; Saraswathy, Kallur Nava; Murry, Benrithung

    2012-10-01

    Hemoglobinopathies are a group of inherited single-gene disorders found commonly in the Mediterranean region, Middle East, Indian subcontinent, Burma, and South East Asia. As many as 229 mutation variants of β-thalassemia are reported in the world, many community/region-specific mutations. Very little on thalassemia has been reported in Manipur, a North Eastern Indian state. Thus, a community genetic approach through population screening can be applied to the people of Manipur and a total of 602 blood samples from unrelated Meitei Brahmins (n=300) and Meitei Muslims (n=302) were screened for abnormal hemoglobins by Naked Eye Single Tube Red Cell Osmotic Fragility Test (NESTROFT). HBA(2) level was estimated by using high-performance liquid chromatography and molecular analysis was done by using PCR. Sequencing was also carried out to confirm the mutations. High frequencies of NESTROFT positive (10%) and NESTROFT doubtful (11%) cases were found among the Meitei Brahmins in comparison to the Meitei Muslims [NESTROFT positive (3.31%) and NESTROFT doubtful (1.33%)]. The allele frequency of HB*E was 0.022 and 0.012 among the Meitei Brahmin and Meitei Muslim, respectively. Sequencing of the β-globin gene confirmed a very rare β-thalassemia [-90 C→T (0.33%)] among the Meitei Brahmins of Manipur. This mutation with hemoglobin E in one of the present population hints the presence of the Mongoloid stock among them, possibly from China. There is a need for further studies on other populations of Manipur and the neighboring North East Indian states using such genetic markers.

  19. Distribution, adaptation and physiological meaning of thiols from vertebrate hemoglobins.

    PubMed

    Reischl, Evaldo; Dafre, Alcir Luiz; Franco, Jeferson Luis; Wilhelm Filho, Danilo

    2007-01-01

    In the present review, the sequences of hemoglobins (Hb) of 267 adult vertebrate species belonging to eight major vertebrate taxa are examined for the presence and location of cysteinyl residues in an attempt at correlation with their ecophysiology. Essentially, all vertebrates have surface cysteinyl residues in Hb molecules whereby their thiol groups may become highly reactive. Thiol-rich Hbs may display eight or more thiols per tetramer. In vertebrates so far examined, the cysteinyl residues occur in 44 different sequence positions in alpha chains and 41 positions in beta chains. Most of them are conservatively located and occur in only a few positions in Teleostei, Aves and Mammalia, whereas they are dispersed in Amphibia. The internal cysteinyl residue alpha104 is ubiquitous in vertebrates. Residue beta93 is highly conserved in reptiles, birds and mammals. The number of cysteine residues per tetramer with solvent access varies in vertebrates, mammalians and bony fish having the lowest number of external residues, whereas nearly all external cysteine residues in Aves and Lepidosauria are of the surface crevice type. In cartilaginous fish, amphibians, Crocodylidae and fresh water turtles, a substantial portion of the solvent accessible thiols are of the totally external type. Recent evidence shows that some Hb thiol groups are highly reactive and undergo extensive and reversible S-thiolation, and that they may be implicated in interorgan redox equilibrium processes. Participation of thiol groups in nitric oxide ((*)NO) metabolism has also been proved. The evidence argues for a new physiologically relevant role for Hb via involvement in free radical and antioxidant metabolism.

  20. Vitreoscilla hemoglobin renders Enterobacter aerogenes highly susceptible to heavy metals.

    PubMed

    Geckil, Hikmet; Arman, Ahmet; Gencer, Salih; Ates, Burhan; Yilmaz, H Ramazan

    2004-12-01

    When expressed in heterologous microorganisms Vitreoscilla hemoglobin (VHb) acts as oxygen storage and causes a higher oxygen uptake. In this study, the effect of this protein on growth, sensitivity and antioxidant properties of Enterobacter aerogenes exposed to metal stress was investigated. The strain expressing VHb was more sensitive to mercury and cadmium as the minimal inhibitory concentration (MIC) for these metals was up to 2-fold lower in this strain than the host and the recombinant strain carrying a comparable plasmid. At lower concentrations than MIC, the metals partially limited growth and caused an inhibition proportional to metal concentration applied. The growth pattern of VHb expressing strain was also distinctly different from other two non-hemoglobin strains. The hemoglobin containing strain showed substantially higher superoxide dismuates (SOD) activity than the non-hemoglobin strains, while catalase levels were similar in all strains. All strains exposed to copper, however, showed similar MIC values, growth patterns, and SOD and catalase levels.

  1. Solid hemoglobin-polymer phantoms for evaluation of biophotonic systems.

    PubMed

    Jang, Hyounguk; Pfefer, T Joshua; Chen, Yu

    2015-09-15

    Stable tissue phantoms that incorporate the spectral absorption properties of hemoglobin would benefit a wide range of biophotonic technologies. Toward this end, we have developed and validated a novel polymer material incorporating hemoglobin. Our solid hemoglobin-polymer (SHP) material is fabricated by mixing liquid silicone base with a hemoglobin solution, followed by sonication and low temperature curing. The optical properties of samples were determined over 450-1000 nm using the inverse adding-doubling method and the Beer-Lambert law. Measurements indicated SHP optical stability over four months. Near-infrared spectroscopy and hyperspectral imaging measurements of SHP samples were performed to demonstrate the utility of this approach. SHP materials have the potential to improve tissue-simulating phantoms used for development, evaluation, and standardization of optical devices for oximetry and other applications.

  2. Weak binding gases as modulators of hemoglobin function

    SciTech Connect

    Schoenborn, B P; Saxena, A; North, B E

    1980-01-01

    Studies are reported in which the mechanisms of binding of inert gaseous agents to hemoglobin and myoglobin are investigated. Specific binding sites are mapped. Possible effects on sickle cell formation and oxygen binding are discussed. (ACR)

  3. Increased Vascular Resistance with Hemoglobin-Based Oxygen Carriers

    DTIC Science & Technology

    1993-01-01

    vascular resistance. Swine resuscitated with otofHb exhibited the rapid onset of marked systemic hypertension . The blood pressure rose within seconds...virtual absence of red blood cells (3), hemoglobin solutions have produced hypertension irn animals or have not supported an increase in cardiac output...with blood volume expansion. Half of all the humans administered hemoglobin in published trials demonstrated hypertension (4), and a recent human

  4. The Manufacture and Study of Hemoglobin-Saline Solution.

    DTIC Science & Technology

    1981-02-25

    The saturation, as measured with the Co-oximeter, was corrected for the proportion of methemoglobin and carboxyhemoglobin , to reflect the per... measurements of the chemical characteristics of the solution during total-exchange transfusion in baboons. These included the monitoring of plasma and...methemoglobin values studied was 7 to 53% of total hemoglobin. 4 A plot of hemoglobin values obtained with the IL 282 (y) vs those measured by the

  5. Neohemoglobins and Cross-Linked Hemoglobins as Blood Substitute.

    DTIC Science & Technology

    1982-12-01

    normal SFH. For bovine hemoglobi, cross-linking of the oxy and carboxy derivatives increased substantially the oxygen affinity and eliminated the oxygen...hemoglobins were prepared by the filtration method. The respective heme-free proteins (apohemoglobins) were prepared by extraction with methyl ...protein. Recombined neohemoglogins and cross-linked hemoglobins were purified by chromatography on CM cellulose using a linear gradient formed by equal

  6. Monoclonal antibodies recognizing single amino acid substitutions in hemoglobin

    SciTech Connect

    Stanker, L.H.; Branscomb, E.; Vanderlaan, M.; Jensen, R.H.

    1986-06-01

    Four monoclonal antibodies (mAb) to non-human primate hemoglobin referred to as Cap-4, Cap-5, Rh-2, and Rh-4, and two mAb to human hemoglobin, referred to as H-1 and H-3 were isolated and were partially characterized. Binding studies with these mAb on a panel of hemoglobins and isolated ..cap alpha.. and ..beta.. globin chains revealed a unique reactivity pattern for each mAb. Amino acid sequence analysis of the antigens used to generate the binding data suggests that the specific recognition of certain hemoglobin antigens by each mAb is controlled by the presence of a particular amino acid at a specific position within the epitope. The use of synthetic peptides as antigens confirmed this observation for five of the mAb. No synthetic peptides were tested with the sixth mAb, Rh-2. The amino acids required for binding of mAb Cap-4, Cap-5, Rh-4, and Rh-2 to hemoglobin are alanine at ..beta..5, threonine at ..beta..13, glutamine at ..beta..125, and leucine at ..cap alpha..68. The non-human primate hemoglobin antibodies require a specific amino acid that is not present in human hemoglobin. The amino acid required for binding of Cap-4, Cap-5, and Rh-4 could arise by a single base change in the ..beta.. globin gene, whereas the amino acid required for Rh-2 binding could only occur if two base changes occurred. Thus these mAb are candidate probes for a somatic cell mutation assay on the basis of the detection of peripheral blood red cells that possess single amino acid substituted hemoglobin as a result of single base substitutions in the globin genes of precursor cells.

  7. Intensive Treatment and Severe Hypoglycemia Among Adults With Type 2 Diabetes

    PubMed Central

    McCoy, Rozalina G.; Lipska, Kasia J.; Yao, Xiaoxi; Ross, Joseph S.; Montori, Victor M.; Shah, Nilay D.

    2017-01-01

    Importance Intensive glucose-lowering treatment among patients with non–insulin-requiring type 2 diabetes may increase the risk of hypoglycemia. Objectives To estimate the prevalence of intensive treatment and the association between intensive treatment, clinical complexity, and incidence of severe hypoglycemia among adults with type 2 diabetes who are not using insulin. Design, Setting, and Participants Retrospective analysis of administrative, pharmacy, and laboratory data from the OptumLabs Data Warehouse from January 1, 2001, through December 31, 2013. The study included nonpregnant adults 18 years or older with type 2 diabetes who achieved and maintained a hemoglobin A1c (HbA1c) level less than 7.0% without use of insulin and had no episodes of severe hypoglycemia or hyperglycemia in the prior 12 months. Main Outcomes and Measures Risk-adjusted probability of intensive treatment and incident severe hypoglycemia, stratified by patient clinical complexity. Intensive treatment was defined as use of more glucose-lowering medications than recommended by practice guidelines at specific index HbA1c levels. Severe hypoglycemia was ascertained by ambulatory, emergency department, and hospital claims for hypoglycemia during the 2 years after the index HbA1c test. Patients were categorized as having high vs low clinical complexity if they were 75 years or older, had dementia or end-stage renal disease, or had 3 or more serious chronic conditions. Results Of 31 542 eligible patients (median age, 58 years; interquartile range, 51–65 years; 15 483 women [49.1%]; 18 188 white [57.7%]), 3910 (12.4%) had clinical complexity. The risk-adjusted probability of intensive treatment was 25.7% (95% CI, 25.1%–26.2%) in patients with low clinical complexity and 20.8% (95% CI, 19.4%–22.2%) in patients with high clinical complexity. In patients with low clinical complexity, the risk-adjusted probability of severe hypoglycemia during the subsequent 2 years was 1.02% (95% CI, 0

  8. Cell volume regulation in hemoglobin CC and AA erythrocytes

    SciTech Connect

    Berkowitz, L.R.; Orringer, E.P.

    1987-03-01

    Swelling hemoglobin CC erythrocytes stimulates a ouabain-insensitive K flux that restores original cell volume. Studies were performed with the K analog, /sup 86/Rb. This volume regulatory pathway was characterized for its anion dependence, sensitivity to loop diuretics, and requirement for Na. The swelling-induced K flux was eliminated if intracellular chloride was replaced by nitrate and both swelling-activated K influx and efflux were partially inhibited by 1 mM furosemide or bumetanide. K influx in swollen hemoglobin CC cells was not diminished when Na in the incubation medium was replaced with choline, indicating Na independence of the swelling-induced flux. Identical experiments with hemoglobin AA cells also demonstrated a swelling-induced increase in K flux, but the magnitude and duration of this increase were considerably less than that seen with hemoglobin CC cells. The increased K flux in hemoglobin AA cells was likewise sensitive to anion replacement and to loop diuretics and did not require the presence of Na. These data indicate that a volume-activated K pathway with similar transport characteristics exists in both hemoglobin CC and AA red cells.

  9. Nitric oxide in plants: the roles of ascorbate and hemoglobin.

    PubMed

    Wang, Xiaoguang; Hargrove, Mark S

    2013-01-01

    Ascorbic acid and hemoglobins have been linked to nitric oxide metabolism in plants. It has been hypothesized that ascorbic acid directly reduces plant hemoglobin in support of NO scavenging, producing nitrate and monodehydroascorbate. In this scenario, monodehydroascorbate reductase uses NADH to reduce monodehydroascorbate back to ascorbate to sustain the cycle. To test this hypothesis, rates of rice nonsymbiotic hemoglobin reduction by ascorbate were measured directly, in the presence and absence of purified rice monodehydroascorbate reductase and NADH. Solution NO scavenging was also measured methodically in the presence and absence of rice nonsymbiotic hemoglobin and monodehydroascorbate reductase, under hypoxic and normoxic conditions, in an effort to gauge the likelihood of these proteins affecting NO metabolism in plant tissues. Our results indicate that ascorbic acid slowly reduces rice nonsymbiotic hemoglobin at a rate identical to myoglobin reduction. The product of the reaction is monodehydroascorbate, which can be efficiently reduced back to ascorbate in the presence of monodehydroascorbate reductase and NADH. However, our NO scavenging results suggest that the direct reduction of plant hemoglobin by ascorbic acid is unlikely to serve as a significant factor in NO metabolism, even in the presence of monodehydroascorbate reductase. Finally, the possibility that the direct reaction of nitrite/nitrous acid and ascorbic acid produces NO was measured at various pH values mimicking hypoxic plant cells. Our results suggest that this reaction is a likely source of NO as the plant cell pH drops below 7, and as nitrite concentrations rise to mM levels during hypoxia.

  10. Hemoglobin Uptake by Paracoccidioides spp. Is Receptor-Mediated

    PubMed Central

    Bailão, Elisa Flávia Luiz Cardoso; Parente, Juliana Alves; Pigosso, Laurine Lacerda; de Castro, Kelly Pacheco; Fonseca, Fernanda Lopes; Silva-Bailão, Mirelle Garcia; Báo, Sônia Nair; Bailão, Alexandre Melo; Rodrigues, Marcio L.; Hernandez, Orville; McEwen, Juan G.; Soares, Célia Maria de Almeida

    2014-01-01

    Iron is essential for the proliferation of fungal pathogens during infection. The availability of iron is limited due to its association with host proteins. Fungal pathogens have evolved different mechanisms to acquire iron from host; however, little is known regarding how Paracoccidioides species incorporate and metabolize this ion. In this work, host iron sources that are used by Paracoccidioides spp. were investigated. Robust fungal growth in the presence of the iron-containing molecules hemin and hemoglobin was observed. Paracoccidioides spp. present hemolytic activity and have the ability to internalize a protoporphyrin ring. Using real-time PCR and nanoUPLC-MSE proteomic approaches, fungal growth in the presence of hemoglobin was shown to result in the positive regulation of transcripts that encode putative hemoglobin receptors, in addition to the induction of proteins that are required for amino acid metabolism and vacuolar protein degradation. In fact, one hemoglobin receptor ortholog, Rbt5, was identified as a surface GPI-anchored protein that recognized hemin, protoporphyrin and hemoglobin in vitro. Antisense RNA technology and Agrobacterium tumefaciens-mediated transformation were used to generate mitotically stable Pbrbt5 mutants. The knockdown strain had a lower survival inside macrophages and in mouse spleen when compared with the parental strain, which suggested that Rbt5 could act as a virulence factor. In summary, our data indicate that Paracoccidioides spp. can use hemoglobin as an iron source most likely through receptor-mediated pathways that might be relevant for pathogenic mechanisms. PMID:24831516

  11. Relative phase of oscillations of cerebral oxy-hemoglobin and deoxy-hemoglobin concentrations during sleep

    NASA Astrophysics Data System (ADS)

    Pierro, Michele L.; Sassaroli, Angelo; Bergethon, Peter R.; Fantini, Sergio

    2012-02-01

    We present a near-infrared spectroscopy study of the instantaneous phase difference between spontaneous oscillations of cerebral deoxy-hemoglobin and oxy-hemoglobin concentrations ([Hb] and [HbO], respectively) in the low-frequency range, namely 0.04-0.12 Hz. We report phase measurements during the transitions between different sleep stages in a whole-night study of a human subject. We have found that the phase difference between [Hb] and [HbO] low-frequency oscillations tends to be greater in deep sleep (by ~96° on average) and REM sleep (by ~77° on average) compared to the awake state. In particular, we have observed progressive phase increases as the subject transitions from awake conditions into non-REM sleep stages N1, N2, and N3. Corresponding phase decreases were recorded in the reversed transitions from sleep stages N3 to N2, and N2 to awake. These results illustrate the physiological information content of phase measurements of [Hb] and [HbO] oscillations that reflect the different cerebral hemodynamic conditions of the different sleep stages, and that can find broader applicability in a wide range of near-infrared spectroscopy brain studies.

  12. A semi-mechanistic model of the relationship between average glucose and HbA1c in healthy and diabetic subjects.

    PubMed

    Lledó-García, Rocío; Mazer, Norman A; Karlsson, Mats O

    2013-04-01

    HbA1c is the most commonly used biomarker for the adequacy of glycemic management in diabetic patients and a surrogate endpoint for anti-diabetic drug approval. In spite of an empirical description for the relationship between average glucose (AG) and HbA1c concentrations, obtained from the A1c-derived average glucose (ADAG) study by Nathan et al., a model for the non-steady-state relationship is still lacking. Using data from the ADAG study, we here develop such models that utilize literature information on (patho)physiological processes and assay characteristics. The model incorporates the red blood cell (RBC) aging description, and uses prior values of the glycosylation rate constant (KG), mean RBC life-span (LS) and mean RBC precursor LS obtained from the literature. Different hypothesis were tested to explain the observed non-proportional relationship between AG and HbA1c. Both an inverse dependence of LS on AG and a non-specificity of the National Glycohemoglobin Standardization Program assay used could well describe the data. Both explanations have mechanistic support and could be incorporated, alone or in combination, in models allowing prediction of the time-course of HbA1c changes associated with changes in AG from, for example dietary or therapeutic interventions, and vice versa, to infer changes in AG from observed changes in HbA1c. The selection between the alternative mechanistic models require gathering of new information.

  13. Interaction between Mean Arterial Pressure and HbA1c in Prediction of Cardiovascular Disease Hospitalisation: A Population-Based Case-Control Study

    PubMed Central

    Yu, Dahai; Zhao, Zhanzheng; Simmons, David

    2016-01-01

    Objective. To explore the relationship between mean arterial pressure (MAP), HbA1c, and cardiovascular (CV) hospitalisation risk in type 2 diabetes. Design. Population-based case-control study. Settings. Primary and secondary care level in Cambridgeshire, United Kingdom. Participants. 588 patients with type 2 diabetes from 18 English general practices recording a CV hospitalisation in 2009–2011 were included. Risk-set sampling was used to select 2920 gender, age, and practice matched control type 2 diabetes patients. Main Outcome Measure. Conditional logistic regression was used to explore further dose-response relationships between MAP, HbA1c, and CV hospitalisation risk. Results. The relationship between MAP and CV hospitalisation was nonlinear (P < 0.001 for linearity test). The MAP associated with the lowest CV hospitalisation risk was 97 (95% CI: 93–101) mmHg. An interaction between MAP and HbA1c for increased risk of cardiovascular hospitalisation was observed among those with HbA1c < 7% (53 mmol/mol) and MAP < 97 mmHg. Conclusions. In type 2 diabetes, MAP is a good predictor of CV hospitalisation risk. CV hospitalisation is lowest with a MAP between 93 and 101 mmHg. CV hospitalisation was particularly high among those with both a low MAP and a lower HbA1c. PMID:27382575

  14. Are the Same Clinical Risk Factors Relevant for Incident Diabetes Defined by Treatment, Fasting Plasma Glucose, and HbA1c?

    PubMed Central

    Balkau, Beverley; Soulimane, Soraya; Lange, Céline; Gautier, Alain; Tichet, Jean; Vol, Sylviane

    2011-01-01

    OBJECTIVE To compare incidences and risk factors for diabetes using seven definitions, with combinations of pharmacological treatment, fasting plasma glucose (FPG) ≥7.0 mmol/L, and HbA1c ≥6.5%. RESEARCH DESIGN AND METHODS Participants aged 30–65 years from the Data from an Epidemiological Study on the Insulin Resistance Syndrome (DESIR) cohort were followed for 9 years. RESULTS More men had incident diabetes as defined by FPG ≥7.0 mmol/L and/or treatment than by HbA1c ≥6.5% and/or treatment: 7.5% (140/1,867) and 5.3% (99/1,874), respectively (P < 0.009); for women incidences were similar: 3.2% (63/1,958) and 3.4% (66/1,954). Known risk factors predicted diabetes for almost all definitions. Among those with incident diabetes by FPG alone versus HbA1c alone, there were more men (78 vs. 35%), case patients were 8 years younger, and fewer were alcohol abstainers (12 vs. 35%) (all P < 0.005). A diabetes risk score discriminated well between those with and without incident diabetes for all definitions. CONCLUSIONS In men, FPG definitions yielded more incident cases of diabetes than HbA1c definitions, in contrast with women. An FPG-derived risk score remained relevant for HbA1c-defined diabetes. PMID:21346181

  15. Generating S-Nitrosothiols from Hemoglobin

    PubMed Central

    Roche, Camille J.; Cassera, Maria B.; Dantsker, David; Hirsch, Rhoda Elison; Friedman, Joel M.

    2013-01-01

    In vitro, ferrous deoxy-hemes in hemoglobin (Hb) react with nitrite to generate nitric oxide (NO) through a nitrite reductase reaction. In vivo studies indicate Hb with nitrite can be a source of NO bioactivity. The nitrite reductase reaction does not appear to account fully for this activity because free NO is short lived especially within the red blood cell. Thus, the exporting of NO bioactivity both out of the RBC and over a large distance requires an additional mechanism. A nitrite anhydrase (NA) reaction in which N2O3, a potent S-nitrosating agent, is produced through the reaction of NO with ferric heme-bound nitrite has been proposed (Basu, S., Grubina, R., Huang, J., Conradie, J., Huang, Z., Jeffers, A., Jiang, A., He, X., Azarov, I., Seibert, R., Mehta, A., Patel, R., King, S. B., Hogg, N., Ghosh, A., Gladwin, M. T., and Kim-Shapiro, D. B. (2007) Nat. Chem. Biol. 3, 785–794) as a possible mechanism. Legitimate concerns, including physiological relevance and the nature of the mechanism, have been raised concerning the NA reaction. This study addresses these concerns demonstrating NO and nitrite with ferric hemes under near physiological conditions yield an intermediate having the properties of the purported NA heme-bound N2O3 intermediate. The results indicate that ferric heme sites, traditionally viewed as a source of potential toxicity, can be functionally significant, especially for partially oxygenated/partially met-R state Hb that arises from the NO dioxygenation reaction. In the presence of low levels of nitrite and either NO or a suitable reductant such as l-cysteine, these ferric heme sites can function as a generator for the formation of S-nitrosothiols such as S-nitrosoglutathione and, as such, should be considered as a source of RBC-derived and exportable bioactive NO. PMID:23775069

  16. Original Research: Generation of non-deletional hereditary persistence of fetal hemoglobin β-globin locus yeast artificial chromosome transgenic mouse models: -175 Black HPFH and -195 Brazilian HPFH

    PubMed Central

    Braghini, Carolina A; Costa, Flavia C; Fedosyuk, Halyna; Neades, Renee Y; Novikova, Lesya V; Parker, Matthew P; Winefield, Robert D

    2016-01-01

    Fetal hemoglobin is a major genetic modifier of the phenotypic heterogeneity in patients with sickle cell disease and certain β-thalassemias. Normal levels of fetal hemoglobin postnatally are approximately 1% of total hemoglobin. Patients who have hereditary persistence of fetal hemoglobin, characterized by elevated synthesis of γ-globin in adulthood, show reduced disease pathophysiology. Hereditary persistence of fetal hemoglobin is caused by β-globin locus deletions (deletional hereditary persistence of fetal hemoglobin) or γ-globin gene promoter point mutations (non-deletional hereditary persistence of fetal hemoglobin). Current research has focused on elucidating the pathways involved in the maintenance/reactivation of γ-globin in adult life. To better understand these pathways, we generated new β-globin locus yeast artificial chromosome transgenic mice bearing the Aγ-globin -175 T > C or -195 C > G hereditary persistence of fetal hemoglobin mutations to model naturally occurring hereditary persistence of fetal hemoglobin. Adult -175 and -195 mutant β-YAC mice displayed a hereditary persistence of fetal hemoglobin phenotype, as measured at the mRNA and protein levels. The molecular basis for these phenotypes was examined by chromatin immunoprecipitation of transcription factor/co-factor binding, including YY1, PAX1, TAL1, LMO2, and LDB1. In -175 HPFH versus wild-type samples, the occupancy of LMO2, TAL1 and LDB1 proteins was enriched in HPFH mice (5.8-fold, 5.2-fold and 2.7-fold, respectively), a result that concurs with a recent study in cell lines showing that these proteins form a complex with GATA-1 to mediate long-range interactions between the locus control region and the Aγ-globin gene. Both hereditary persistence of fetal hemoglobin mutations result in a gain of Aγ-globin activation, in contrast to other hereditary persistence of fetal hemoglobin mutations that result in a loss of repression. The mice provide additional tools to study

  17. Dithionite Tube Test - A Rapid, Inexpensive Technique for the Detection of Hemoglobin S and Non-S Sickling Hemoglobin.

    DTIC Science & Technology

    hemoglobinopathies of low solubility such as Kings County and Stanleyville II. The dithionite and urea-dithionite tests, however, will provide rapid, accurate, reliable, and inexpensive screening for hemoglobin S. (Author)

  18. Identification of a haptoglobin-hemoglobin complex in the Alaskan Least Cisco (Coregonus sardinella).

    PubMed

    Wahl, S M; Boger, J K; Michael, V; Duffy, L K

    1992-01-01

    The hemoglobin and a hemoglobin binding protein have been characterized in the Arctic fish (Coregonus sardinella). The evolutionary significance of the hemoglobin and plasma protein differences between fish and mammals is still unresolved. Blood samples from the Alaskan Least Cisco were separated into plasma and hemoglobin fractions and the proteins in these fractions were analyzed both by alkaline agarose gel electrophoresis, by isolelectric focusing, and by capillary electrophoresis. Staining the plasma proteins gels with o-dianisidine revealed hemoglobin containing protein complexes. A hemoglobin-containing band was observed in hemolyzed plasma which did not migrate with free hemoglobin, and is believed to be hemoglobin-haptoglobin complex. Size exclusion chromatography further characterized the hemoglobin as disassociating freely into dimers, and hemoglobin-haptoglobin complex having a molecular weight greater then 200,000 daltons.

  19. Molecular and physicochemical characterization of hemoglobin from the high-altitude Taiwanese brown-toothed shrew (Episoriculus fumidus).

    PubMed

    Campbell, Kevin L; Signore, Anthony V; Harada, Masashi; Weber, Roy E

    2012-08-01

    Red-toothed shrews (subfamily Soricinae) exhibit the highest mass-specific rates of O₂ consumption recorded among eutherian mammals, though surprisingly no data appears to be available on the functional characteristics of their hemoglobin (Hb). As a first step in addressing this shortcoming, we investigated the O₂ binding characteristics of Taiwanese brown-toothed shrew (Episoriculus fumidus) Hb and its temperature and pH dependence in the absence and presence of anionic red blood cell effectors. Although comparative data regarding the intrinsic O₂ affinity of other shrew species are currently unavailable, our data suggest that the sensitivity of this high-elevation endemic species' Hb to allosteric effector molecules is similar to that of the two lowland species of white-toothed (crocidurine) shrews examined to date. The efficient exploitation of blood O₂ reserves by E. fumidus appears to be achieved via synergistic modulation of O₂ affinity by Cl⁻ and organic phosphates that moreover dramatically lowers the overall enthalpy of oxygenation of their Hb. Oxygen unloading is presumably further enhanced by a relatively high Bohr effect (ΔLog P₅₀/ΔpH = -0.69) and marked reduction in the titratable histidine content (predicted low proton buffering value) of the component globin chains relative to human HbA. Notably, however, the limited data available suggest these latter attributes may be widespread among shrews and hence likely are not adaptations to chronic altitudinal hypoxia per se.

  20. A molecular study of a family with Greek hereditary persistence of fetal hemoglobin and beta-thalassemia.

    PubMed

    Giglioni, B; Casini, C; Mantovani, R; Merli, S; Comi, P; Ottolenghi, S; Saglio, G; Camaschella, C; Mazza, U

    1984-11-01

    A family was studied in which two inherited defects of the non-alpha-globin cluster segregate: Greek hereditary persistence of fetal hemoglobin (HPFH) and beta-thalassemia. Fragments of the non-alpha-globin cluster from two patients were cloned in cosmid and phage lambda vectors, and assigned to either the HPFH or beta-thalassemic chromosome on the basis of the demonstration of a polymorphic BglII site in the HPFH gamma-globin cluster. The thalassemic beta-globin gene carries a mutation at nucleotide 1 of the intervening sequence I, known to cause beta zero-thalassemia; the beta-globin gene from the HPFH chromosome is entirely normal, both in the intron-exon sequence and in 5' flanking regions required for transcription. As the compound HPFH/beta-thalassemia heterozygote synthesizes HbA, these data prove that the HPFH beta-globin gene is functional, although at a decreased rate; its lower activity is likely to be due to a distant mutation. The HPFH A gamma-globin gene shows only two mutations: a T----C substitution in the large intervening sequence (responsible for the BglII polymorphic site) and a C----T substitution 196 nucleotides 5' to the cap site; the 5' flanking sequence is normal up to -1350 nucleotides upstream from the gene. Circumstantial evidence suggests that the mutation at -196 may be responsible for the abnormally high expression of the A gamma-globin gene.

  1. Lyophilized bovine hemoglobin as a possible reference material for the determination of hemoglobin derivatives in human blood.

    PubMed

    Maas, B H; Buursma, A; Ernst, R A; Maas, A H; Zijlstra, W G

    1998-11-01

    We investigated the suitability of a lyophilized bovine hemoglobin (LBH) preparation containing various fractions of oxyhemoglobin (O2Hb), carboxyhemoglobin (COHb), and methemoglobin (MetHb) for quality assessment in multicomponent analysis (MCA) of hemoglobin derivatives. It was demonstrated that a stable preparation of these components after reconstitution yields a hemoglobin solution that is spectrophotometrically equivalent with a fresh bovine hemoglobin solution. The preparation was found to be stable for at least 1 year when it is kept at 2-8 degrees C and for 1 h after reconstitution. We determined the fractions of O2Hb, COHb, and MetHb of several LBH preparations, using the complete spectra of 480-650 nm with 2-nm intervals and absorptivities as determined for pure LBH solutions. A field trial involving various types of multiwavelength hemoglobin photometers showed the suitability of LBH as a quality-control material. Computer models of the various common multiwavelength hemoglobin photometers may be useful for establishing more accurate target values of LBH preparations for each type of photometer and for studying the importance of the influence of specific factors such as wavelength selection, absorptivity values, and interfering dyes.

  2. Analysis of Chlorination, Nitration, and Nitrosylation of Tyrosine and Oxidation of Methionine and Cysteine in Hemoglobin from Type 2 Diabetes Mellitus Patients by Nanoflow Liquid Chromatography Tandem Mass Spectrometry.

    PubMed

    Chen, Hauh-Jyun Candy; Yang, Ya-Fen; Lai, Pang-Yen; Chen, Pin-Fan

    2016-09-20

    The post-translational modification (PTM) of proteins by endogenous reactive chlorine, nitrogen, and oxygen species is implicated in certain pathological conditions, including diabetes mellitus. Evidence showed that the extents of modifications on a number of proteins are elevated in diabetic patients. Measuring modification on hemoglobin has been used to monitor the extent of exposure. This study develops an assay for simultaneous quantification of the extent of chlorination, nitration, and oxidation in human hemoglobin and to examine whether the level of any of these modifications is higher in poorly controlled type 2 diabetic mellitus patients. This mass spectrometry-based assay used the bottom-up proteomic strategy. Due to the low amount of endogenous modification, we first characterized the sites of chlorination at tyrosine in hypochlorous acid-treated hemoglobin by an accurate mass spectrometer. The extents of chlorination, nitration, and oxidation of a total of 12 sites and types of modifications in hemoglobin were measured by nanoflow liquid chromatography-nanospray ionization tandem mass spectrometry under the selected reaction monitoring mode. Relative quantification of these PTMs in hemoglobin extracted from blood samples shows that the extents of chlorination at α-Tyr-24, nitration at α-Tyr-42, and oxidation at the three methionine residues are significantly higher in diabetic patients (n = 19) than in nondiabetic individuals (n = 18). After excluding the factor of smoking, chlorination at α-Tyr-24, nitration at α-Tyr-42, and oxidation at the three methionine residues are significantly higher in the nonsmoking diabetic patients (n = 12) than in normal nonsmoking subjects (n = 11). Multiple regression analysis performed on the combined effect of age, body-mass index (BMI), and HbA1c showed that the diabetes factor HbA1c contributes significantly to the extent of chlorination at α-Tyr-24 in nonsmokers. In addition, age contributes to oxidation at

  3. Quantification of extra-cerebral and cerebral hemoglobin concentrations during physical exercise using time-domain near infrared spectroscopy.

    PubMed

    Auger, Héloïse; Bherer, Louis; Boucher, Étienne; Hoge, Richard; Lesage, Frédéric; Dehaes, Mathieu

    2016-10-01

    Fitness is known to have beneficial effects on brain anatomy and function. However, the understanding of mechanisms underlying immediate and long-term neurophysiological changes due to exercise is currently incomplete due to the lack of tools to investigate brain function during physical activity. In this study, we used time-domain near infrared spectroscopy (TD-NIRS) to quantify and discriminate extra-cerebral and cerebral hemoglobin concentrations and oxygen saturation (SO2) in young adults at rest and during incremental intensity exercise. In extra-cerebral tissue, an increase in deoxy-hemoglobin (HbR) and a decrease in SO2 were observed while only cerebral HbR increased at high intensity exercise. Results in extra-cerebral tissue are consistent with thermoregulatory mechanisms to dissipate excess heat through skin blood flow, while cerebral changes are in agreement with cerebral blood flow (CBF) redistribution mechanisms to meet oxygen demand in activated regions during exercise. No significant difference was observed in oxy- (HbO2) and total hemoglobin (HbT). In addition HbO2, HbR and HbT increased with subject's peak power output (equivalent to the maximum oxygen volume consumption; VO2 peak) supporting previous observations of increased total mass of red blood cells in trained individuals. Our results also revealed known gender differences with higher hemoglobin in men. Our approach in quantifying both extra-cerebral and cerebral absolute hemoglobin during exercise may help to better interpret past and future continuous-wave NIRS studies that are prone to extra-cerebral contamination and allow a better understanding of acute cerebral changes due to physical exercise.

  4. Quantification of extra-cerebral and cerebral hemoglobin concentrations during physical exercise using time-domain near infrared spectroscopy

    PubMed Central

    Auger, Héloïse; Bherer, Louis; Boucher, Étienne; Hoge, Richard; Lesage, Frédéric; Dehaes, Mathieu

    2016-01-01

    Fitness is known to have beneficial effects on brain anatomy and function. However, the understanding of mechanisms underlying immediate and long-term neurophysiological changes due to exercise is currently incomplete due to the lack of tools to investigate brain function during physical activity. In this study, we used time-domain near infrared spectroscopy (TD-NIRS) to quantify and discriminate extra-cerebral and cerebral hemoglobin concentrations and oxygen saturation (SO2) in young adults at rest and during incremental intensity exercise. In extra-cerebral tissue, an increase in deoxy-hemoglobin (HbR) and a decrease in SO2 were observed while only cerebral HbR increased at high intensity exercise. Results in extra-cerebral tissue are consistent with thermoregulatory mechanisms to dissipate excess heat through skin blood flow, while cerebral changes are in agreement with cerebral blood flow (CBF) redistribution mechanisms to meet oxygen demand in activated regions during exercise. No significant difference was observed in oxy- (HbO2) and total hemoglobin (HbT). In addition HbO2, HbR and HbT increased with subject’s peak power output (equivalent to the maximum oxygen volume consumption; VO2 peak) supporting previous observations of increased total mass of red blood cells in trained individuals. Our results also revealed known gender differences with higher hemoglobin in men. Our approach in quantifying both extra-cerebral and cerebral absolute hemoglobin during exercise may help to better interpret past and future continuous-wave NIRS studies that are prone to extra-cerebral contamination and allow a better understanding of acute cerebral changes due to physical exercise. PMID:27867696

  5. Hemoglobin Wood beta97(FG4) His replaced by Leu. A new high-oxygen-affinity hemoglobin associated with familial erythrocytosis.

    PubMed

    Taketa, F; Huang, Y P; Libnoch, J A; Dessel, B H

    1975-08-19

    The characterization of hemoglobin Wood (beta97(FG4) His replaced by Leu), a high oxygen affinity hemoglobin with reduced Hill constant is described. The amino acid substitution occurs at the alpha1beta2 interface, in the same position as in hemoglobin Malmö (beta97(FG4) His replaced by Gln) and in an homologous position when compared with hemoglobins Chesapeake (alpha92(FG4) Arg replaced by Leu) and J. Capetown (alpha92(fg4) arg replaced by Gln).

  6. Structural transition temperature of hemoglobins correlates with species' body temperature.

    PubMed

    Zerlin, Kay Frank Thorsten; Kasischke, Nicole; Digel, Ilya; Maggakis-Kelemen, Christina; Temiz Artmann, Aysegül; Porst, Dariusz; Kayser, Peter; Linder, Peter; Artmann, Gerhard Michael

    2007-12-01

    Human red blood cells (RBCs) exhibit sudden changes in their biophysical properties at body temperature (T (B)). RBCs were seen to undergo a spontaneous transition from blockage to passage at T (C) = 36.4 +/- 0.3 degrees C, when the temperature dependency of RBC-passages through 1.3 mum narrow micropipettes was observed. Moreover, concentrated hemoglobin solutions (45 g/dl) showed a viscosity breakdown between 36 and 37 degrees C. With human hemoglobin, a structural transition was observed at T (B) as circular dichroism (CD) experiments revealed. This leads to the assumption that a species' body temperature occupies a unique position on the temperature scale and may even be imprinted in the structure of certain proteins. In this study, it was investigated whether hemoglobins of species with a T (B) different from those of human show temperature transitions and whether those were also linked to the species' T (B). The main conclusion was drawn from dynamic light scattering (DLS) and CD experiments. It was observed that such structural temperature transitions did occur in hemoglobins from all studied species and were correlated linearly (slope 0.81, r = 0.95) with the species' body temperature. We presumed that alpha-helices of hemoglobin were able to unfold more readily around T (B). alpha-helical unfolding would initiate molecular aggregation causing RBC passage and viscosity breakdown as mentioned above. Thus, structural molecular changes of hemoglobin could determine biophysical effects visible on a macroscopic scale. It is hypothesized that the species' body temperature was imprinted into the structure of hemoglobins.

  7. The effect of nano-curcumin on HbA1c, fasting blood glucose, and lipid profile in diabetic subjects: a randomized clinical trial

    PubMed Central

    Rahimi, Hamid Reza; Mohammadpour, Amir Hooshang; Dastani, Mostafa; Jaafari, Mahmoud Reza; Abnous, Khalil; Ghayour Mobarhan, Majid; Kazemi Oskuee, Reza

    2016-01-01

    Objective: Diabetes mellitus is defined as a group of metabolic diseases characterized by hyperglycemia resulting from defects in insulin secretion, insulin action, or both or insulin resistance. Curcumin inhibits NF-κB signaling pathway. The aim of this study is evaluation of the effect of Nano-curcumin on HbA1C, fast blood glucose and lipid profile in diabetic patients. Materials and Methods: Seventy type-2 diabetic patients (fasting blood glucose (FBG) ≥ 126 mg/dL or 2-hr postprandial blood glucose ≥200 mg/dl) randomly receivedeither Curcumin (as nano-micelle 80 mg/day) or placebo for 3 months in a double blind randomized clinical trial. Fasting blood glucose, HbA1C, and lipids profile were checked before and after the intervention. Data analyses, including parametric and nonparametric tests were done using the SPSS 11.5 software. A p value < 0.05 was regarded as statistically significant. (RCT registration code: IRCT2013081114330N1) Results: Mean age, BMI, FBG, total cholesterol (TC), triglyceride (TG), LDL, HDL, HbA1c , and sex and had no significant difference at the baseline between the groups. In Nano-curcumin group, a significant decrease was found in HbA1C, FBG, TG, and BMI comparing results of each subject before and after the treatment (p<0.05). By comparing pre- and post-treatment values among the groups, HbA1c, eAG, LDL-C, and BMI variables showed significant differences (p<0.05). Conclusion: These findings suggest an HbA1c lowering effect for Nano-curcumin in type-2 diabetes; also, it is partially decrease in serum LDL-C and BMI. PMID:27761427

  8. Comparative analysis of cellulose acetate hemoglobin electrophoresis and high performance liquid chromatography for quantitative determination of hemoglobin A2

    PubMed Central

    Khosa, Shafi Mohammad; Moinuddin, Moinuddin; Mehmood, Hassan Osman; Qamar, Khansa

    2015-01-01

    Background The present study is designed to evaluate the reliability and cost effectiveness of cellulose acetate Hb electrophoresis and high performance liquid chromatography (HPLC) in the determination of HbA2 levels. Methods The test population comprised 160 individuals divided into four groups: normal individuals, β-thalassemia trait (BTT) patients, iron deficiency anemia (IDA) patients, and co-morbid patients (BTT with IDA). HbA2 levels determined using cellulose acetate Hb electrophoresis and HPLC were compared. Results HbA2 levels were found to be diagnostic for classical BTT using either method. In co-morbid cases, both techniques failed to diagnose all cases of BTT. The sensitivity, specificity, and Youden's index for detection of the co-morbid condition was 69% and 66% for HPLC and cellulose acetate Hb electrophoresis, respectively. Conclusion This study revealed that semi-automated cellulose acetate Hb electrophoresis is more suitable for use in β-thalassemia prevention programs in low-income countries like Pakistan. This technique is easily available, simple and cost effective. PMID:25830130

  9. Peptide nucleic acids targeting β-globin mRNAs selectively inhibit hemoglobin production in murine erythroleukemia cells

    PubMed Central

    MONTAGNER, GIULIA; GEMMO, CHIARA; FABBRI, ENRICA; MANICARDI, ALEX; ACCARDO, IGEA; BIANCHI, NICOLETTA; FINOTTI, ALESSIA; BREVEGLIERI, GIULIA; SALVATORI, FRANCESCA; BORGATTI, MONICA; LAMPRONTI, ILARIA; BRESCIANI, ALBERTO; ALTAMURA, SERGIO; CORRADINI, ROBERTO; GAMBARI, ROBERTO

    2015-01-01

    In the treatment of hemoglobinopathies, amending altered hemoglobins and/or globins produced in excess is an important part of therapeutic strategies and the selective inhibition of globin production may be clinically beneficial. Therefore the development of drug-based methods for the selective inhibition of globin accumulation is required. In this study, we employed peptide nucleic acids (PNAs) to alter globin gene expression. The main conclusion of the present study was that PNAs designed to target adult murine β-globin mRNA inhibit hemoglobin accumulation and erythroid differentiation of murine erythroleukemia (MEL) cells with high efficiency and fair selectivity. No major effects were observed on cell proliferation. Our study supports the concept that PNAs may be used to target mRNAs that, similar to globin mRNAs, are expressed at very high levels in differentiating erythroid cells. Our data suggest that PNAs inhibit the excess production of globins involved in the pathophysiology of hemoglobinopathies. PMID:25405921

  10. Hemoglobin research and the origins of molecular medicine

    PubMed Central

    2008-01-01

    Much of our understanding of human physiology, and of many aspects of pathology, has its antecedents in laboratory and clinical studies of hemoglobin. Over the last century, knowledge of the genetics, functions, and diseases of the hemoglobin proteins has been refined to the molecular level by analyses of their crystallographic structures and by cloning and sequencing of their genes and surrounding DNA. In the last few decades, research has opened up new paradigms for hemoglobin related to processes such as its role in the transport of nitric oxide and the complex developmental control of the α-like and β-like globin gene clusters. It is noteworthy that this recent work has had implications for understanding and treating the prevalent diseases of hemoglobin, especially the use of hydroxyurea to elevate fetal hemoglobin in sickle cell disease. It is likely that current research will also have significant clinical implications, as well as lessons for other aspects of molecular medicine, the origin of which can be largely traced to this research tradition. PMID:18988877

  11. Electrospray ionization mass spectrometric characterization of acrylamide adducts to hemoglobin

    SciTech Connect

    Springer, D.L.; Goheen, S.C.; Edmonds, C.G. ); Bull, R.J.; Sylvester, D.M. )

    1993-01-01

    The most common procedure to identify hemoglobin adducts has been to cleave the adducts from the protein and characterize the adducting species, by, for example, derivatization and gas chromatography/mass spectrometry. To extend these approaches we used electrospray ionization mass spectrometry (ESI-MS) to characterize adducted hemoglobin. For this we incubated [[sup 14]C]acrylamide with the purified human hemoglobin (type A[sub 0]) under conditions that yielded high adduct levels. When the hemoglobin was separated by reversed-phase high-performance liquid chromatography (HPLC), 65% of the radioactivity copurified with the [beta]-subunit. Three adducted species were prominent in the ESI mass spectrum of the intact [beta]-subunit, indicating acrylamide adduction (i.e., mass increase of 71 Da) and two addition unidentified moieties with mass increments of 102 and 135 Da. Endoproteinase Glu-C digestion of the adducted [beta]-subunit resulted in a peptide mixture that, upon reversed-phase HPLC separation, provided several radiolabeled peptides. Using ESI-MS we identified these as the V[sub 91-101] and V[sub 102-122] peptides that represent the cysteine-containing peptides of the [beta]-subunit. These results provide definitive information on acrylamide-modified human hemoglobin and demonstrate that ESI-MS provides valuable structure information on chemically adducted proteins. 30 refs., 9 figs., 3 tabs.

  12. Therapeutic hemoglobin levels after gene transfer in β-thalassemia mice and in hematopoietic cells of β-thalassemia and sickle cells disease patients.

    PubMed

    Breda, Laura; Casu, Carla; Gardenghi, Sara; Bianchi, Nicoletta; Cartegni, Luca; Narla, Mohandas; Yazdanbakhsh, Karina; Musso, Marco; Manwani, Deepa; Little, Jane; Gardner, Lawrence B; Kleinert, Dorothy A; Prus, Eugenia; Fibach, Eitan; Grady, Robert W; Giardina, Patricia J; Gambari, Roberto; Rivella, Stefano

    2012-01-01

    Preclinical and clinical studies demonstrate the feasibility of treating β-thalassemia and Sickle Cell Disease (SCD) by lentiviral-mediated transfer of the human β-globin gene. However, previous studies have not addressed whether the ability of lentiviral vectors to increase hemoglobin synthesis might vary in different patients.We generated lentiviral vectors carrying the human β-globin gene with and without an ankyrin insulator and compared their ability to induce hemoglobin synthesis in vitro and in thalassemic mice. We found that insertion of an ankyrin insulator leads to higher, potentially therapeutic levels of human β-globin through a novel mechanism that links the rate of transcription of the transgenic β-globin mRNA during erythroid differentiation with polysomal binding and efficient translation, as reported here for the first time. We also established a preclinical assay to test the ability of this novel vector to synthesize adult hemoglobin in erythroid precursors and in CD34(+) cells isolated from patients affected by β-thalassemia and SCD. Among the thalassemic patients, we identified a subset of specimens in which hemoglobin production can be achieved using fewer copies of the vector integrated than in others. In SCD specimens the treatment with AnkT9W ameliorates erythropoiesis by increasing adult hemoglobin (Hb A) and concurrently reducing the sickling tetramer (Hb S).Our results suggest two major findings. First, we discovered that for the purpose of expressing the β-globin gene the ankyrin element is particularly suitable. Second, our analysis of a large group of specimens from β-thalassemic and SCD patients indicates that clinical trials could benefit from a simple test to predict the relationship between the number of vector copies integrated and the total amount of hemoglobin produced in the erythroid cells of prospective patients. This approach would provide vital information to select the best candidates for these clinical trials

  13. Therapeutic Hemoglobin Levels after Gene Transfer in β-Thalassemia Mice and in Hematopoietic Cells of β-Thalassemia and Sickle Cells Disease Patients

    PubMed Central

    Breda, Laura; Casu, Carla; Gardenghi, Sara; Bianchi, Nicoletta; Cartegni, Luca; Narla, Mohandas; Yazdanbakhsh, Karina; Musso, Marco; Manwani, Deepa; Little, Jane; Gardner, Lawrence B.; Kleinert, Dorothy A.; Prus, Eugenia; Fibach, Eitan; Grady, Robert W.; Giardina, Patricia J.; Gambari, Roberto; Rivella, Stefano

    2012-01-01

    Preclinical and clinical studies demonstrate the feasibility of treating β-thalassemia and Sickle Cell Disease (SCD) by lentiviral-mediated transfer of the human β-globin gene. However, previous studies have not addressed whether the ability of lentiviral vectors to increase hemoglobin synthesis might vary in different patients. We generated lentiviral vectors carrying the human β-globin gene with and without an ankyrin insulator and compared their ability to induce hemoglobin synthesis in vitro and in thalassemic mice. We found that insertion of an ankyrin insulator leads to higher, potentially therapeutic levels of human β-globin through a novel mechanism that links the rate of transcription of the transgenic β-globin mRNA during erythroid differentiation with polysomal binding and efficient translation, as reported here for the first time. We also established a preclinical assay to test the ability of this novel vector to synthesize adult hemoglobin in erythroid precursors and in CD34+ cells isolated from patients affected by β-thalassemia and SCD. Among the thalassemic patients, we identified a subset of specimens in which hemoglobin production can be achieved using fewer copies of the vector integrated than in others. In SCD specimens the treatment with AnkT9W ameliorates erythropoiesis by increasing adult hemoglobin (Hb A) and concurrently reducing the sickling tetramer (Hb S). Our results suggest two major findings. First, we discovered that for the purpose of expressing the β-globin gene the ankyrin element is particularly suitable. Second, our analysis of a large group of specimens from β-thalassemic and SCD patients indicates that clinical trials could benefit from a simple test to predict the relationship between the number of vector copies integrated and the total amount of hemoglobin produced in the erythroid cells of prospective patients. This approach would provide vital information to select the best candidates for these clinical trials

  14. Hemoglobin stimulates mononuclear leukocytes to release interleukin-8 and tumor necrosis factor alpha.

    PubMed

    McFaul, S J; Bowman, P D; Villa, V M; Gutierrez-Ibanez, M J; Johnson, M; Smith, D

    1994-11-01

    Incubation of human mononuclear leukocytes (MNL) with human stroma-free hemolysate (SFH), purified adult hemoglobin Ao (HbAo), and oxidized HbAo (METHb) caused MNL to release compounds into the supernate that mediated neutrophil (polymorphonuclear leukocytes, PMN) chemotaxis and PMN adherence to human umbilical vein endothelial cells (HUVEC). Chemotaxis and PMN adherence to HUVEC were reduced significantly when supernates were preincubated with neutralizing antibodies to interleukin-8 (IL-8) and tumor necrosis factor alpha (TNF-alpha), respectively, suggesting that IL-8 and TNF-alpha played significant roles in mediating these activities. Greatest chemotactic activity was observed in supernates of MNL treated with HbAo; while greatest PMN/endothelial cell (EC) adherence activity was observed in supernates of MNL treated with METHb. Furthermore, PMN/EC adherence activity was a function of METHb content in each hemoglobin solution. PMN chemotaxis, PMN adherence to HUVEC, and cytokine release increased as a function of increasing incubation time. Chemotactic activity was detected in HbAo-treated and METHb-treated MNL supernates after incubation for 6 hours and was maximal by 10 hours. IL-8 was detected in both HbAo and METHb-MNL supernates by 4 hours. PMN/EC adherence activity was detected in HbAo-MNL supernates at 10 hours and in METHb-MNL supernates at 4 hours. TNF-alpha was detected in METHb and HbAo-MNL supernates at 4 and 12 hours, respectively. These results suggest that hemoglobin solutions stimulate MNL to release IL-8 and TNF-alpha in quantities sufficient to induce PMN chemotaxis and PMN adherence to HUVEC. This is a US government work. There are no restrictions on its use.

  15. Plant hemoglobins: important players at the crossroads between oxygen and nitric oxide.

    PubMed

    Gupta, Kapuganti J; Hebelstrup, Kim H; Mur, Luis A J; Igamberdiev, Abir U

    2011-12-15

    Plant hemoglobins constitute a diverse group of hemeproteins and evolutionarily belong to three different classes. Class 1 hemoglobins possess an extremely high affinity to oxygen and their main function consists in scavenging of nitric oxide (NO) at very low oxygen levels. Class 2 hemoglobins have a lower oxygen affinity and they facilitate oxygen supply to developing tissues. Symbiotic hemoglobins in nodules have mostly evolved from class 2 hemoglobins. Class 3 hemoglobins are truncated and represent a clade with a very low similarity to class 1 and 2 hemoglobins. They may regulate oxygen delivery at high O(2) concentrations. Depending on their physical properties, hemoglobins belong either to hexacoordinate non-symbiotic or pentacoordinate symbiotic groups. Plant hemoglobins are plausible targets for improving resistance to multiple stresses.

  16. Membrane-associated sickle hemoglobin: a major determinant of sickle erythrocyte rigidity.

    PubMed

    Evans, E A; Mohandas, N

    1987-11-01

    Micropipette aspiration tests on single erythrocytes have previously shown that the static rigidity (membrane shear modulus) of oxygenated sickle cells increased with increasing hemoglobin concentration, whereas the rigidity of normal cells was independent of hemoglobin concentration. Moreover, it was observed that after mechanical extension, sickle cells exhibited persistent deformation more frequently and to a greater extent than normal cells. To ascertain if differences in association of normal and sickle hemoglobin with the membrane could account for these observations, we measured rheologic properties of normal membranes reconstituted with sickle hemoglobin and sickle membranes reconstituted with normal hemoglobin. The static rigidity of normal ghosts reloaded with sickle hemoglobin was higher than those of either normal ghosts reloaded with normal hemoglobin or native normal cells. On the other hand, the increased rigidity of native sickle cells decreased to near-normal values following reconstitution with normal hemoglobin. Furthermore, we observed that normal ghosts reconstituted with sickle hemoglobin exhibited persistent bumps after mechanical extension, but no bumps formed on normal ghosts reconstituted with normal hemoglobin. Moreover residual bumps were not produced on sickle cells reloaded with normal hemoglobin. Since mechanical characteristics peculiar to sickle cells could be induced in normal cells by incorporation of sickle hemoglobin, and since normal characteristics could be restored to sickle cells by incorporation of normal hemoglobin, we suggest that the interaction of sickle hemoglobin with the cell membrane is responsible for augmented static rigidity of oxygenated sickle erythrocytes.

  17. Mastomys (rodentia: muridae) species distinguished by hemoglobin pattern differences.

    PubMed

    Robbins, C B; Krebs, J W; Johnson, K M

    1983-05-01

    Hemoglobin electrophoresis patterns were found to be reliable markers for distinguishing two species of Mastomys in Sierra Leone having 32 and 38 chromosomes. All 32-chromosome animals exhibited a single hemoglobin pattern, whereas those with 38-chromosomes had four distinguishable patterns. Both karyotypes were present throughout Sierra Leone. The 38-chromosome species was more prevalent in the Guinea savanna zone to the north, while the 32-chromosome species was most dominant in human-modified high forest areas of the eastern and southern parts of the country. In almost all situations the 32-chromosome species was more common in houses than in bush habitats; the reverse was true for Mastomys having 38 chromosomes. Analysis of hemoglobin patterns thus becomes useful for species identification, and is necessary to understand the roles of the different Mastomys forms as reservoirs of human diseases, such as Lassa fever in West Africa.

  18. Hemoglobin Koya Dora: high frequency of a chain termination mutant.

    PubMed Central

    De Jong, W W; Meera Khan, P; Bernini, L F

    1975-01-01

    Approximately 10% of the members of the Koya Dora tribe from Andhra Pradesh (India) carry an alpha chain hemoglobin variant, Hb Koya Dora (Hb KD), usually in amounts of 0.5%-2% of total hemoglobin. In four presumed homozygotes for Hb KD, up to 10% of the abnormal hemoglobin was present. The alpha chain of Hb KD was found to be elongated by at least 16 residues, possibly as a result of a mutation of the normal alpha chain termination codon UAA TO UCA, coding for serine. A pedigree in which two individuals possess Hb KD as well as the alpha chain variant Hb Rampa and normal Hb A proves the existence of two alpha chain loci in this population. Hb DK resembles the previously described Hb Constant Spring [6, 7] in many aspects, probably also in its alpha thalassemia-like expression. Images Fig. 1 Fig. 2 PMID:1155453

  19. Iron Deficiency in Adolescents and Young Adults.

    ERIC Educational Resources Information Center

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

    1990-01-01

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

  20. Electrochemical behavior of immobilized hemoglobin in alkaline solution

    NASA Astrophysics Data System (ADS)

    Jović-Jovičić, Nataša; Mojović, Zorica; Mojović, Miloš; Banković, Predrag; Ajduković, Marija; Milutinović-Nikolić, Aleksandra; Jovanović, Dušan

    2017-04-01

    Glassy carbon electrode was modified with different synthesized hybrid clay-based materials and tested in alkaline solution with and without H2O2. The hybrid materials were obtained by immobilizing hemoglobin (Hb) on acid activated (AA) clay, or on AA clay modified with different sodium dodecyl sulfate (SDS) loadings. The obtained materials were characterized using DR UV-vis and ESR spectroscopy, elemental analysis, and SEM. The characterization confirmed higher degree of hemoglobin incorporation in the presence of SDS. The presence of SDS on the surface of clay particles resulted in the partial oxidation/denaturation of hemoglobin and formation of hemichrome. Cyclic voltammetry was used for the investigation of the electrochemical behavior of immobilized hemoglobin in alkaline solution. Two cathodic peaks at -0.45 V and -0.70 V were recorded and ascribed to the reduction of heme Fe(III)/Fe(II), and formation of HbFe(I) - highly reduced form of hemoglobin - respectively. The latter peak reflects hemoglobin denaturation. The presence of H2O2 in the alkaline solution increased current intensities corresponding to both peaks (-0.45 V and -0.7 V). Linear response of peak current intensity vs. H2O2 concentration was monitored for all investigated samples within different H2O2 concentration ranges. The AA-SDS1.0-Hb electrode exhibited the highest current response with linear regression equation in the following form: I(μA) = 7.99 + 1.056 × [H2O2] (mM) (R = 0.996). The limit of detection of 28 μM was estimated using the 3 sigma method. Different modified electrodes exhibited different degrees of denaturation resistance. The obtained values of Michaelis-Menten constant indicated that prolonged cycling in the presence of SDS increases protein denaturation.