Glycation precedes lens crystallin aggregation

International Nuclear Information System (INIS)

Swamy, M.S.; Perry, R.E.; Abraham, E.C.

1987-01-01

Non-enzymatic glycosylation (glycation) seems to have the potential to alter the structure of crystallins and make them susceptible to thiol oxidation leading to disulfide-linked high molecular weight (HMW) aggregate formation. They used streptozotocin diabetic rats during precataract and cataract stages and long-term cell-free glycation of bovine lens crystallins to study the relationship between glycation and lens crystallin aggregation. HMW aggregates and other protein components of the water-soluble (WS) and urea-soluble (US) fractions were separated by molecular sieve high performance liquid chromatography. Glycation was estimated by both [ 3 H]NaBH 4 reduction and phenylboronate agarose affinity chromatography. Levels of total glycated protein (GP) in the US fractions were about 2-fold higher than in the WS fractions and there was a linear increase in GP in both WS and US fractions. This increase was parallelled by a corresponding increase in HMW aggregates. Total GP extracted by the affinity method from the US fraction showed a predominance of HMW aggregates and vice versa. Cell-free glycation studies with bovine crystallins confirmed the results of the animals studies. Increasing glycation caused a corresponding increase in protein insolubilization and the insoluble fraction thus formed also contained more glycated protein. It appears that lens protein glycation, HMW aggregate formation, and protein insolubilization are interrelated

In vitro determination of hemoglobin A1c for diabetes diagnosis and management: technology update

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English E

2014-07-01

Full Text Available Emma English,1 Elise T Milosevich,1 W Garry John2 1School of Medicine, University of Nottingham, Royal Derby Hospital, Derby, United Kingdom; 2Department of Clinical Biochemistry, Norfolk and Norwich University Hospital, Norwich, United Kingdom Abstract: It is fascinating to consider the analytical improvements that have occurred since glycated hemoglobin was first used in routine clinical laboratories for diabetes monitoring around 1977; at that time methods displayed poor precision, there were no calibrators or material with assayed values for quality control purposes. This review outlines the major improvements in hemoglobin A1c (HbA1c measurement that have occurred since its introduction, and reflects on the increased importance of this hemoglobin fraction in the monitoring of glycemic control. The use of HbA1c as a diagnostic tool is discussed in addition to its use in monitoring the patient with diabetes; the biochemistry of HbA1c formation is described, and how these changes to the hemoglobin molecule have been used to develop methods to measure this fraction. Standardization of HbA1c is described in detail; the development of the IFCC Reference Measurement Procedure for HbA1c has enabled global standardization to be achieved which has allowed global targets to be set for glycemic control and diagnosis. The importance of factors that may interfere in the measurement of HbA1c are highlighted. Keywords: glycated hemoglobin, HbA1c, IFCC

Association of glycated hemoglobin with carotid intimal medial thickness in Asian Indians with normal glucose tolerance.

Science.gov (United States)

Venkataraman, Vijayachandrika; Amutha, Anandakumar; Anbalagan, Viknesh Prabu; Deepa, Mohan; Anjana, Ranjit Mohan; Unnikrishnan, Ranjit; Vamsi, Mamilla; Mohan, Viswananthan

2012-01-01

To assess the association of glycated hemoglobin (HbA1c) levels with carotid intimal medial thickness (CIMT) in Asian Indians with normal glucose tolerance (NGT). Subjects with NGT were recruited from the Chennai Urban Rural Epidemiology Study carried out on a representative population of Chennai, South India. All subjects had fasting plasma glucose right common carotid artery using high-resolution B-mode ultrasonography. The study group included 1383 NGT subjects, of whom 760 (54.9%) were women. The mean CIMT value in the 1st quartile of HbA1c (5.8) (prights reserved.

Influence of insulin sensitivity and secretion on glycated albumin and hemoglobin A1c in pregnant women with gestational diabetes mellitus.

Science.gov (United States)

Pan, Jiemin; Zhang, Feng; Zhang, Lei; Bao, Yuqian; Tao, Minfang; Jia, Weiping

2013-06-01

To examine the differential effects of insulin sensitivity and secretion on hemoglobin A1c (HbA1c) and glycated albumin (GA) at 24-32weeks of pregnancy in women with gestational diabetes mellitus (GDM). A cross-sectional, sequential case series study was performed in pregnant women with an abnormal 50-g oral glucose-screening test. Hemoglobin A1c and GA measurements were taken during oral glucose tolerance test (OGTT). The homeostasis model assessment of insulin resistance (HOMA-IR) and beta-cell function (HOMA-%β), insulin sensitivity index (ISOGTT), and modified insulinogenic index were calculated to assess insulin sensitivity and secretory function. A total of 713 pregnant women were enrolled. The GDM group had lower ISOGTT and insulinogenic index scores, and a higher HOMA-IR score. Hemoglobin A1c was positively correlated with HOMA-IR. Glycated albumin was negatively correlated with insulinogenic index and HOMA-%β. Multiple regression analysis revealed that HbA1c was independently associated with diastolic pressure, 0- and 120-minute glucose, and HOMA-IR; GA was independently associated with 0- and 120-minute glucose. Compared with HbA1c, GA is more closely correlated with fasting and postprandial glucose, regardless of insulin resistance and blood pressure, and might be a better monitoring index in women with GDM. Copyright © 2013 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

Trend of glycated hemoglobin testing in diabetic patients: to assess compliance with clinical practice guidelines

International Nuclear Information System (INIS)

Ghayur, S.; Tariq, H.

2013-01-01

Objective: To determine appropriate use of glycated hemoglobin (HbA1c) testing in accordance with current recommended guidelines. Study Design: Descriptive study. Place and Duration of Study: Chemical Pathology Department Shifa International Hospital, Islamabad from Oct 2011 to Oct 2012. Material and Methods: We randomly selected 170 known diabetic patients' data from our Laboratory Information System (LIS) who were retrospective analyzed for HbA1c to check for intervals and test frequency for each patient in one year. Patients with follow-up for at least one year at Shifa International Hospital, Islamabad and having their routine investigations in our chemical pathology laboratory were included. The concentrations of HbA1c for all the specimens were measured immunoturbidimetrically using a microparticle agglutination inhibition method. Four guidelines namely World Health Organization (WHO), American Diabetic Association (ADA), Canadian Diabetic Association (CDA) and National Institute for Health and Clinical Excellence (NICE) about HbA1c testing were utilized for data interpretation. All tests ordered within a 2 months period or more than 6 months following the previous order were labeled as inappropriate. Results: Only 35.8% of the patients were being properly monitored as per guidelines. Out of 64% patients who were inappropriately monitored, 12.9% had repeat orders within 2 months while 51.1% of patients were being monitored at longer interval against recommended guidelines. Conclusions: Glycated hemoglobin is a useful tool to objectively assess the prior glycemic control of patients with type 1 and type 2 diabetes. The study highlights that in large proportion of diabetic patients, HbA1c is not utilized properly as a tool to assess the risk of diabetic complications but in a small proportion is also tested unnecessarily which adds to avoidable health expenditure. (author)

Plasma disappearance of glycated and non-glycated albumin in type 1 (insulin-dependent) diabetes mellitus

DEFF Research Database (Denmark)

Bent-Hansen, L; Feldt-Rasmussen, B; Kverneland, Arne

1993-01-01

transport ratio) was determined from the disappearance data. The index was high in control subjects (1.021 +/- 0.0057 (SEM)). This reflects a mean difference between the two escape rates of 2.1% per hour (for comparison the mean of the fractional escape rate of non-glycated albumin of the normal control......The fractional plasma escape rates of glycated and non-glycated albumin have earlier been measured in groups of Type 1 (insulin-dependent) diabetic patients and control subjects. The escape of non-glycated albumin was similar in control subjects and normoalbuminuric patients, but elevated...... in patients with micro or macroalbuminuria. In all groups the escape rate of glycated albumin was lower than that of non-glycated albumin. Glycation increases the anionic charge of albumin. To assay for charge-dependent alterations of transport a selectivity index (non-glycated albumin/glycated albumin...

Glycated Hemoglobin Is Associated With the Growth Rate of Abdominal Aortic Aneurysms

DEFF Research Database (Denmark)

Kristensen, Katrine Lawaetz; Dahl, Marie; Rasmussen, Lars Melholt

2017-01-01

and HbA1c in the total study population (P=0.002). Both crude and adjusted analyses identified slower growth for the group with the highest HbA1c tertile compared with the lowest HbA1c tertile. After 3 years, the mean difference was 1.8 mm (confidence interval, 0.98–2.64). Similar significant differences......OBJECTIVE—: An inverse association between abdominal aortic aneurysms (AAAs) and diabetes mellitus exists; however, the cause remains unknown. This study aimed to evaluate whether the degree of glycemia is associated with aneurysm growth. APPROACH AND RESULTS—: The study was based on VIVA trial...... (Viborg Vascular), the randomized clinically controlled screening trial for abdominal aortic aneurysm in men aged 65 to 74 years in the Central Denmark Region. The screening included measurement of the abdominal aorta by ultrasound, analysis of glycated hemoglobin (HbA1c), and follow-up for ≤5 years...

Inhibition of protein glycation and advanced glycation end products ...

African Journals Online (AJOL)

Fatima

2012-06-26

Jun 26, 2012 ... acid (AA) can react with proteins, including hemoglobin and possibly interfere with protein glycation process. .... 50 mM) and AA (100, 200, 300 and 400 mM) at 37°C for five weeks ... drops were removed by patting the plate over a paper towel. The .... adults participating in the Beaver Dam Eye Study. In.

Effects of thyroid status on glycated hemoglobin

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Rana Bhattacharjee

2017-01-01

Full Text Available 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.

Streptozotocin-induced Diabetic Effects on the Sperm Fertility Parameters, Glycated Hemoglobin and Total Cholesterol in Mice

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A Sookhthezari

2016-01-01

(R2=0.90, P=0.012 was depicted between HbA1c and sperm concentration in the diabetic group. Epithelial vaculization of semineferous tubules was observed in the diabetic group in comparison with the control group and epidydimal ducts indicated increased volume of spermatoza in the controls when compared to the diabetic rats. Conclusion: As the study findings revealed diabetes was associated with decreased sperm concentration in the cauda epididymis even two weeks after hyperglycemia induction, which can be mentioned as a predective index for subfertility. Furthermore, Glycated hemoglobin revealed a negetive relationship with sperm concentration. Hypercholestrolemia was also shown in early stages of diabetes indicating an impairment in lipids metabolism, which was confirmed by the histology changes.

Raman Spectroscopy Provides a Powerful Diagnostic Tool for Accurate Determination of Albumin Glycation

OpenAIRE

Dingari, Narahara Chari; Kang, Jeon Woong; Dasari, Ramachandra R.; Barman, Ishan; Horowitz, Gary Leigh

2012-01-01

We present the first demonstration of glycated albumin detection and quantification using Raman spectroscopy without the addition of reagents. Glycated albumin is an important marker for monitoring the long-term glycemic history of diabetics, especially as its concentrations, in contrast to glycated hemoglobin levels, are unaffected by changes in erythrocyte life times. Clinically, glycated albumin concentrations show a strong correlation with the development of serious diabetes complications...

The Glycated Albumin to Glycated Hemoglobin Ratio Might Not Be Associated with Carotid Atherosclerosis in Patients with Type 1 Diabetes

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Wonjin Kim

2014-12-01

Full Text Available BackgroundThe ratio of glycated albumin to glycated hemoglobin (GA/A1c is known to be elevated in subjects with type 2 diabetes mellitus (T2DM who had decreased insulin secretion. Additionally, the carotid intima media thickness (IMT is greater in T2DM patients with higher GA/A1c ratios. We investigated whether increased GA/A1c ratio and IMT are also associated in type 1 diabetes mellitus (T1DM, which is characterized by lack of insulin secretory capacity.MethodsIn this cross-sectional study, we recruited 81 T1DM patients (33 men, 48 women; mean age 44.1±13.0 years who underwent carotid IMT, GA, and HbA1c measurements.ResultsThe mean GA/A1c ratio was 2.90. Based on these results, we classified the subjects into two groups: group I (GA/A1c ratio <2.90, n=36 and group II (GA/A1c ratio ≥2.90, n=45. Compared with group I, the body mass indexes (BMIs, waist circumferences, and IMTs were lower in group II. GA/A1c ratio was negatively correlated with BMI, urine albumin to creatinine ratio (P<0.001 for both, and both the mean and maximal IMT (P=0.001, both. However, after adjusting the confounding factors, we observed that IMT was no longer associated with GA/A1c ratio.ConclusionIn contrast to T2DM, IMT was not significantly related to GA/A1c ratio in the subjects with T1DM. This suggests that the correlations between GA/A1c ratio and the parameters known to be associated with atherosclerosis in T2DM could be manifested differently in T1DM. Further studies are needed to investigate these relationships in T1DM.

Can glycated hemoglobin act as a reliable glycemic indicator in patients with diabetic chronic kidney disease? evidence from the Northeast of Thailand

OpenAIRE

Sojib Bin Zaman; Naznin Hossain; Ahmed E. Rahman; Sheikh M.S. Islam

2017-01-01

Background: Chronic kidney diseases (CKD) is a common microvascular complication in patients with diabetes mellitus (DM) which requires adequate glycemic control. Glycated hemoglobin (HbA1c) is a conventional biomarker to estimate glycemic status, but its role in diabetic CKD patients is unclear. Therefore, this study aimed to determine whether patients with high HbA1c are associated to develop diabetic CKD.Methods: Data were obtained from a clinical registry of diabetic patients who were tre...

Isotope effects in the non enzymic glycation of hemoglobin catalyzed by DPG

International Nuclear Information System (INIS)

Gil, Herminia; Uzcategui, Jorge

1993-01-01

The paradigmatic reaction of glucose with hemoglobin (Hb A o ) has been studied and is known to occur most rapidly at the N-terminal valine of the β-subunit. An initial, rapid imine formation is succeeded by slower Amadori rearrangement. Non enzymic glycation of Hb A o was studied in vitro in buffer Tris 10 mM in H 2 O and D 2 O, pH 7.3, pD 7.8 at 37 deg C at a fixed concentration of 2,3 diphosphoglycerate (DPG). The reaction exhibits identical rates in protium and deuterium oxides. When D-glucose-2-h is compared with D-glucose-2-d, the kinetic isotope effect for the DPG-dependent rate is 2.1 ± 0.3, while the DPG-independent rate constant shows no isotope effect (1.1 ± 0.1). The absence of a rate in isotopic water solvents shows that proton donation for solvent, lyons or DPG does not limit the rate. The substrate isotope effect of around 2 for the DPG kinetic term indicates that the proton abstraction step of the Amadori rearrangement by DPG is wholly or partially rate-limiting for this reaction. (author)

Determination of glycated hemoglobin in patients with advanced liver disease

Science.gov (United States)

Lahousen, Theresa; Hegenbarth, Karin; Ille, Rottraut; Lipp, Rainer W.; Krause, Robert; Little, Randie R.; Schnedl, Wolfgang J.

2004-01-01

AIM: To evaluate the glycated hemoglobin (HbA 1c) determination methods and to determine fructosamine in patients with chronic hepatitis, compensated cirrhosis and in patients with chronic hepatitis treated with ribavirin. METHODS: HbA1c values were determined in 15 patients with compensated liver cirrhosis and in 20 patients with chronic hepatitis using the ion-exchange high performance liquid chromatography and the immunoassay methods. Fructosamine was determined using nitroblue tetrazolium. RESULTS: Forty percent of patients with liver cirrhosis had HbA1c results below the non-diabetic reference range by at least one HbA1c method, while fructosamine results were either within the reference range or elevated. Twenty percent of patients with chronic hepatitis (hepatic fibrosis) had HbA1c results below the non -diabetic reference range by at least one HbA1c method. In patients with chronic hepatitis treated with ribavirin, 50% of HbA1c results were below the non-diabetic reference using at least one of the HbA1c methods. CONCLUSION: Only evaluated in context with all liver function parameters as well as a red blood count including reticulocytes, HbA 1c results should be used in patients with advanced liver disease. HbA 1c and fructosamine measurements should be used with caution when evaluating long-term glucose control in patients with hepatic cirrhosis or in patients with chronic hepatitis and ribavirin treatment. PMID:15259084

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

Science.gov (United States)

Al-Hakeim, Hussein Kadhem; Abdulzahra, Mohammed Saied

2015-04-01

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. 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. 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. 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.

Hemoglobin fructation promotes heme degradation through the generation of endogenous reactive oxygen species

Science.gov (United States)

Goodarzi, M.; Moosavi-Movahedi, A. A.; Habibi-Rezaei, M.; Shourian, M.; Ghourchian, H.; Ahmad, F.; Farhadi, M.; Saboury, A. A.; Sheibani, N.

2014-09-01

Protein glycation is a cascade of nonenzymatic reactions between reducing sugars and amino groups of proteins. It is referred to as fructation when the reducing monosaccharide is fructose. Some potential mechanisms have been suggested for the generation of reactive oxygen species (ROS) by protein glycation reactions in the presence of glucose. In this state, glucose autoxidation, ketoamine, and oxidative advance glycation end products (AGEs) formation are considered as major sources of ROS and perhaps heme degradation during hemoglobin glycation. However, whether fructose mediated glycation produces ROS and heme degradation is unknown. Here we report that ROS (H2O2) production occurred during hemoglobin fructation in vitro using chemiluminescence methods. The enhanced heme exposure and degradation were determined using UV-Vis and fluorescence spectrophotometry. Following accumulation of ROS, heme degradation products were accumulated reaching a plateau along with the detected ROS. Thus, fructose may make a significant contribution to the production of ROS, glycation of proteins, and heme degradation during diabetes.

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

Science.gov (United States)

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

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. 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. 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 Indian pregnant women, a HbA1c of 5.0% (31 mmol/mol) or greater is associated with increased risk of macrosomia.

Isotope effects in the non enzymic glycation of hemoglobin catalyzed by DPG

Energy Technology Data Exchange (ETDEWEB)

Gil, Herminia; Uzcategui, Jorge [Universidad de Los Andes, Merida (Venezuela). Dept. de Quimica

1993-12-31

The paradigmatic reaction of glucose with hemoglobin (Hb A{sub o}) has been studied and is known to occur most rapidly at the N-terminal valine of the {beta}-subunit. An initial, rapid imine formation is succeeded by slower Amadori rearrangement. Non enzymic glycation of Hb A{sub o} was studied in vitro in buffer Tris 10 mM in H{sub 2} O and D{sub 2} O, pH 7.3, pD 7.8 at 37 deg C at a fixed concentration of 2,3 diphosphoglycerate (DPG). The reaction exhibits identical rates in protium and deuterium oxides. When D-glucose-2-h is compared with D-glucose-2-d, the kinetic isotope effect for the DPG-dependent rate is 2.1 {+-} 0.3, while the DPG-independent rate constant shows no isotope effect (1.1 {+-} 0.1). The absence of a rate in isotopic water solvents shows that proton donation for solvent, lyons or DPG does not limit the rate. The substrate isotope effect of around 2 for the DPG kinetic term indicates that the proton abstraction step of the Amadori rearrangement by DPG is wholly or partially rate-limiting for this reaction. (author) 23 refs., 4 figs.

Common Variants at 10 Genomic Loci Influence Hemoglobin A(1C) Levels via Glycemic and Nonglycemic Pathways

NARCIS (Netherlands)

Soranzo, Nicole; Sanna, Serena; Wheeler, Eleanor; Gieger, Christian; Radke, Doerte; Dupuis, Josee; Bouatia-Naji, Nabila; Langenberg, Claudia; Prokopenko, Inga; Stolerman, Elliot; Sandhu, Manjinder S.; Heeney, Matthew M.; Devaney, Joseph M.; Reilly, Muredach P.; Ricketts, Sally L.; Stewart, Alexandre F. R.; Voight, Benjamin F.; Willenborg, Christina; Wright, Benjamin; Altshuler, David; Arking, Dan; Balkau, Beverley; Barnes, Daniel; Boerwinkle, Eric; Boehm, Bernhard; Bonnefond, Amelie; Bonnycastle, Lori L.; Boomsma, Dorret I.; Boinstein, Stefan R.; Boettcher, Yvonne; Bumpstead, Suzannah; Burnett-Miller, Mary Susan; Campbell, Harry; Cao, Antonio; Chambers, John; Clark, Robert; Collins, Francis S.; Coresh, Josef; de Geus, Eco J. C.; Dei, Mariano; Deloukas, Panos; Doering, Angela; Egan, Josephine M.; Elosua, Roberto; Ferrucci, Luigi; Forouhi, Nita; Fox, Caroline S.; Franklin, Christopher; Zhao, Jing Hua; van der Hout, Annemarie

2010-01-01

OBJECTIVE-Glycated hemoglobin (HbA(1c)), 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 HbA(1c). We aimed to

The ethyl acetate fraction of corn silk exhibits dual antioxidant and anti-glycation activities and protects insulin-secreting cells from glucotoxicity.

Science.gov (United States)

Chang, Chia-Chuan; Yuan, Wei; Roan, Hsiao-Yuh; Chang, Jia-Ling; Huang, Hsiu-Chen; Lee, Yu-Ching; Tsay, Huey Jen; Liu, Hui-Kang

2016-11-03

In this study, we aimed to develop a Stigmata Maydis (corn silk) fraction with dual bio-activities against oxidative stress and protein glycation to protect β-cells from diabetes-induced failure. Corn silk fractions were prepared by partition and chemically characterised by thin-layer chromatography. Free radical scavenging assay, glycation assay, and cell-based viability test (neutral red) were employed to decide the best fraction. Cell death analysis was executed by annexin V/ Propidium iodide staining. Cell proliferation was measured by WST-1. Finally, β-cell function was evaluated by β-cell marker gene expression (RT-PCR) and acute insulin secretion test. Four corn silk fractions were prepared from an ethanolic crude extract of corn silk. In vitro assays indicate ethyl acetate fraction (YMS-EA) was the most potent fraction. YMS-EA also attenuated the hydrogen peroxide- or methylglyoxal-induced induction of reactive oxygen species, reduction of cell viability, and inhibition of cell proliferation. However, YMS-EA was unable to prevent hydrogen peroxide-induced apoptosis or advanced glycation end-products-induced toxicity. Under hyperglycemic conditions, YMS-EA effectively reduced ROS levels, improved mRNA expression of insulin, glucokinase, and PDX-1, and enhanced glucose-stimulated insulin secretion. The similarity of bioactivities among apigenin, luteolin, and YMS-EA indicated that dual activities of YMS-EA might be derived from those compounds. We concluded that YMS-EA fraction could be developed as a preventive food agent against the glucotoxicity to β-cells in Type 2 diabetes.

Raman spectroscopy provides a powerful diagnostic tool for accurate determination of albumin glycation.

Science.gov (United States)

Dingari, Narahara Chari; Horowitz, Gary L; Kang, Jeon Woong; Dasari, Ramachandra R; Barman, Ishan

2012-01-01

We present the first demonstration of glycated albumin detection and quantification using Raman spectroscopy without the addition of reagents. Glycated albumin is an important marker for monitoring the long-term glycemic history of diabetics, especially as its concentrations, in contrast to glycated hemoglobin levels, are unaffected by changes in erythrocyte life times. Clinically, glycated albumin concentrations show a strong correlation with the development of serious diabetes complications including nephropathy and retinopathy. In this article, we propose and evaluate the efficacy of Raman spectroscopy for determination of this important analyte. By utilizing the pre-concentration obtained through drop-coating deposition, we show that glycation of albumin leads to subtle, but consistent, changes in vibrational features, which with the help of multivariate classification techniques can be used to discriminate glycated albumin from the unglycated variant with 100% accuracy. Moreover, we demonstrate that the calibration model developed on the glycated albumin spectral dataset shows high predictive power, even at substantially lower concentrations than those typically encountered in clinical practice. In fact, the limit of detection for glycated albumin measurements is calculated to be approximately four times lower than its minimum physiological concentration. Importantly, in relation to the existing detection methods for glycated albumin, the proposed method is also completely reagent-free, requires barely any sample preparation and has the potential for simultaneous determination of glycated hemoglobin levels as well. Given these key advantages, we believe that the proposed approach can provide a uniquely powerful tool for quantification of glycation status of proteins in biopharmaceutical development as well as for glycemic marker determination in routine clinical diagnostics in the future.

Raman Spectroscopy Provides a Powerful Diagnostic Tool for Accurate Determination of Albumin Glycation

Science.gov (United States)

Dingari, Narahara Chari; Horowitz, Gary L.; Kang, Jeon Woong; Dasari, Ramachandra R.; Barman, Ishan

2012-01-01

We present the first demonstration of glycated albumin detection and quantification using Raman spectroscopy without the addition of reagents. Glycated albumin is an important marker for monitoring the long-term glycemic history of diabetics, especially as its concentrations, in contrast to glycated hemoglobin levels, are unaffected by changes in erythrocyte life times. Clinically, glycated albumin concentrations show a strong correlation with the development of serious diabetes complications including nephropathy and retinopathy. In this article, we propose and evaluate the efficacy of Raman spectroscopy for determination of this important analyte. By utilizing the pre-concentration obtained through drop-coating deposition, we show that glycation of albumin leads to subtle, but consistent, changes in vibrational features, which with the help of multivariate classification techniques can be used to discriminate glycated albumin from the unglycated variant with 100% accuracy. Moreover, we demonstrate that the calibration model developed on the glycated albumin spectral dataset shows high predictive power, even at substantially lower concentrations than those typically encountered in clinical practice. In fact, the limit of detection for glycated albumin measurements is calculated to be approximately four times lower than its minimum physiological concentration. Importantly, in relation to the existing detection methods for glycated albumin, the proposed method is also completely reagent-free, requires barely any sample preparation and has the potential for simultaneous determination of glycated hemoglobin levels as well. Given these key advantages, we believe that the proposed approach can provide a uniquely powerful tool for quantification of glycation status of proteins in biopharmaceutical development as well as for glycemic marker determination in routine clinical diagnostics in the future. PMID:22393405

Heterozygote Hemoglobin G-Coushatta as the Cause of a Falsely Decreased Hemoglobin A1C in an Ion-Exchange HPLC Method

Directory of Open Access Journals (Sweden)

Kurtoğlu Ayşegül Uğur

2017-09-01

Full Text Available Glycated hemoglobin (HbA1c is used for the assessment of glycemic control in patients with diabetes. The presence of genetic variants of hemoglobin can profoundly affect the accuracy of HbA1c measurement. Here, we report two cases of Hemoglobin G-Coushatta (HBB:c.68A>C variant that interferes in the measurement of HbA1c by a cation-exchange HPLC (CE-HPLC method. HbA1c was measured by a CE-HPLC method in a Tosoh HLC-723 G7 instrument. The HbA1c levels were 2.9% and 4%. These results alerted us to a possible presence of hemoglobinopathy. In the hemoglobin variant analysis, HbA2 levels were detected as 78.3% and 40.7% by HPLC using the short program for the Biorad Variant II. HbA1c levels were measured by an immunoturbidimetric assay in a Siemens Dimension instrument. HbA1c levels were reported as 5.5% and 5.3%. DNA mutation analysis was performed to detect the abnormal hemoglobin variant. Presence of Hemoglobin G-Coushatta variant was detected in the patients. The Hb G-Coushatta variants have an impact on the determination of glycated hemoglobin levels using CEHPLC resulting in a false low value. Therefore, it is necessary to use another measurement method.

Comprehensive Identification of Glycated Peptides and Their Glycation Motifs in Plasma and Erythrocytes of Control and Diabetic Subjects

Energy Technology Data Exchange (ETDEWEB)

Zhang, Qibin; Monroe, Matthew E.; Schepmoes, Athena A.; Clauss, Therese RW; Gritsenko, Marina A.; Meng, Da; Petyuk, Vladislav A.; Smith, Richard D.; Metz, Thomas O.

2011-07-01

Non-enzymatic glycation of proteins is implicated in diabetes mellitus and its related complications. In this report, we extend our previous development and refinement of proteomics-based methods for the analysis of non-enzymatically glycated proteins to comprehensively identify glycated proteins in normal and diabetic human plasma and erythrocytes. Using immunodepletion, enrichment, and fractionation strategies, we identified 7749 unique glycated peptides, corresponding to 3742 unique glycated proteins. Semi-quantitative comparisons revealed a number of proteins with glycation levels significantly increased in diabetes relative to control samples and that erythrocyte proteins are more extensively glycated than plasma proteins. A glycation motif analysis revealed amino acids that are favored more than others in the protein primary structures in the vicinity of the glycation sites in both sample types. The glycated peptides and corresponding proteins reported here provide a foundation for the potential identification of novel markers for diabetes, glycemia, or diabetic complications.

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

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Yu-Wei Chen

Full Text Available 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.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.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.The HGI index derived from FPG and HbA1c may be able to identify who will have a better response to DPP-4 inhibitors.

PSEUDOAFFINITY CHROMATOGRAPHY ENRICHMENT OF GLYCATED PEPTIDES FOR MONITORING ADVANCED GLYCATION END PRODUCTS (AGES IN METABOLIC DISORDERS

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Rajasekar R. Prasanna

2016-09-01

Full Text Available Advanced Glycation End (AGE products are produced due to diabetic progression and they are responsible for many complications in the diabetic disorder. The diabetic progression is measured, particularly following glycated hemoglobin using specific antibodies. However, the most abundant protein in blood, human serum albumin, is also found to be glycated which has a much shorter half life and gives information on short term glycemic control. In addition, glycated albumins are considered as markers of diabetic complications such as nephropathy, peripheral vascular calcification and also in Alzheimer’s disease. The glycation proceeds from the interaction between aldehyde group of sugar and the free amino group of the protein, resulting in the formation of Schiff’s base, which undergoes a series of modifications leading to generation of imidazoyl derivatives of amino acids known as Amadori rearrangement products. The imidazoyl derivatives from arginine and lysine are the most prominent modifications observed in proteins in the presence of reducing sugar and these imidazoyl derivatives have an affinity towards certain transition metal ions. Based on our earlier exhaustive work on trapping the histidine peptides using transition metal ion, Cu(II linked to imino-diacetate complex, we explored Cu(II immobilized metal affinity chromatography (IMAC as a potential tool for specific detection of glycated peptides of human serum albumin. Our results clearly demonstrate that Cu(II IMAC is able to detect glycated peptides very efficiently while the non-glycated forms were not retained on the Cu (II column as confirmed by LC-MS/MS analysis. We further discuss the utility of IMAC technology to enrich the detection of AGE products in plasma. We anticipate that these studies may provide valuable information on understanding disease pathologies and the potential of AGE products as biomarkers of various diseases including neurodegenerative, renal and

Prediction model for high glycated hemoglobin concentration among ethnic Chinese in Taiwan

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Lee Bai-Chin

2010-09-01

Full Text Available Abstract Background This study aimed to construct a prediction model to identify subjects with high glycated hemoglobin (HbA1c levels by incorporating anthropometric, lifestyle, clinical, and biochemical information in a large cross-sectional ethnic Chinese population in Taiwan from a health checkup center. Methods The prediction model was derived from multivariate logistic regression, and we evaluated the performance of the model in identifying the cases with high HbA1c levels (> = 7.0%. In total 17,773 participants (age > = 30 years were recruited and 323 participants (1.8% had high HbA1c levels. The study population was divided randomly into two parts, with 80% as the derivation data and 20% as the validation data. Results The point-based clinical model, including age (maximal 8 points, sex (1 point, family history (3 points, body mass index (2 points, waist circumference (4 points, and systolic blood pressure (3 points reached an area under the receiver operating characteristic curve (AUC of 0.723 (95% confidence interval, 0.677- 0.769 in the validation data. Adding biochemical measures such as triglycerides and HDL cholesterol improved the prediction power (AUC, 0.770 [0.723 - 0.817], P = Conclusions A prediction model was constructed for the prevalent risk of high HbA1c, which could be useful in identifying high risk subjects for diabetes among ethnic Chinese in Taiwan.

Association of grade of non-alcoholic fatty liver disease and glycated albumin to glycated hemoglobin ratio in patients with type 2 diabetes mellitus.

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Jung, Chan-Hee; Lee, Bora; Choi, Dug-Hyun; Jung, Sang-Hee; Kim, Bo-Yeon; Kim, Chul-Hee; Kang, Sung-Koo; Mok, Ji-Oh

2017-03-01

The aim of this study was to investigate the association between the glycated albumin (GA) to glycated hemoglobin (HbA1c) (GA/HbA1c) ratio and grade of non-alcoholic fatty liver disease (NAFLD) on ultrasonography (US) in patients with type 2 diabetes mellitus (T2DM). This retrospective, cross-sectional study was performed with data obtained from 186 T2DM patients. Participants were assessed for serum GA/HbA1c ratio and fatty liver using US. NAFLD was defined as ultrasonographically detected fatty liver and was graded as normal, mild, moderate, and severe fatty liver. A total of 98 subjects (53%) were diagnosed with NAFLD on US, of which 47 (48%) had moderate-to-severe grade of NAFLD. The mean GA level and GA/HbA1c ratio significantly decreased across increasing NAFLD stages (34% vs. 29% vs. 27% vs. 28%, p=0.023 for trend; 3.1vs. 2.9vs. 2.6vs. 2.7, p=0.001 for trend, respectively), whereas there was no significant difference in HbA1c level among groups (p=0.714 for trend). There was a significant decrease in prevalence of NAFLD across GA/HbA1c ratio tertiles (67% vs. 58% vs. 41%, p for trend=0.007). Multivariate logistic regression analysis showed that individuals with the lowest GA/HbA1c ratio had an odds ratio (OR) of 2.75 (95% CI=1.06-7.13) for having any grade of NAFLD and an OR of 4.48 [1.20-16.74] for moderate-to-severe grade NAFLD compared with the highest GA/HbA1c ratio even after adjustment for confounding factors (p=0.038, p=0.026, respectively). The present study showed that GA/HbA1c ratio was significantly inversely associated with the presence and severity of NAFLD on US. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Association Between Coronary Artery Calcification and the Hemoglobin Glycation Index: The Kangbuk Samsung Health Study.

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Rhee, Eun-Jung; Cho, Jung-Hwan; Kwon, Hyemi; Park, Se Eun; Park, Cheol-Young; Oh, Ki-Won; Park, Sung-Woo; Lee, Won-Young

2017-12-01

The hemoglobin glycation index (HGI) is known to be correlated with the risk for cardiovascular disease. To analyze the association between incident coronary artery calcification (CAC) and the changes in HGI among participants without diabetes, over 4 years. A retrospective study of 2052 nondiabetic participants in whom the coronary artery calcium score was measured repeatedly over 4 years, as part of a health checkup program in Kangbuk Samsung Hospital in Korea, and who had no CAC at baseline. The HGI was defined as the difference between the measured and predicted hemoglobin A1c (HbA1c) levels. A total of 201 participants developed CAC after 4 years, and the mean baseline HGI was significantly higher in those patients. The incidence of CAC gradually increased from the first to the fourth quartile groups of baseline HGI. The odds ratio (OR) for incident CAC was the highest among the four groups divided by the quartiles of the baseline HGI and was significant after adjustment for confounding variables (vs first quartile group: OR, 1.632; 95% confidence interval, 1.024 to 2.601). The incidence of and risk for CAC development were significantly higher than in other groups compared with the low-to-low group after adjustment for confounding factors; however, when baseline HbA1c level was included in the model, only participants with a low-to-high HGI over 4 years showed a significantly increased OR for CAC development compared with the low-to-low group (OR, 1.722; 95% confidence interval, 1.046 to 2.833). The participants with a high baseline HGI and consistently high HGI showed a higher risk for incident CAC than those with a low baseline HGI. An increased HGI over 4 years significantly increased the risk for CAC regardless of the baseline HbA1c levels. Copyright © 2017 Endocrine Society

Molten globule of hemoglobin proceeds into aggregates and advanced glycated end products.

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Afshin Iram

Full Text Available Conformational alterations of bovine hemoglobin (Hb upon sequential addition of glyoxal over a range of 0-90% v/v were investigated. At 20% v/v glyoxal, molten globule (MG state of Hb was observed by altered tryptophan fluorescence, high ANS binding, existence of intact heme, native-like secondary structure as depicted by far-UV circular dichroism (CD and ATR-FTIR spectra as well as loss in tertiary structure as confirmed by near-UV CD spectra. In addition, size exclusion chromatography analysis depicted that MG state at 20% v/v glyoxal corresponded to expanded pre-dissociated dimers. Aggregates of Hb were detected at 70% v/v glyoxal. These aggregates of Hb had altered tryptophan environment, low ANS binding, exposed heme, increased β-sheet secondary structure, loss in tertiary structure, enhanced thioflavin T (ThT fluorescence and red shifted Congo Red (CR absorbance. On incubating Hb with 30% v/v glyoxal for 0-20 days, advanced glycation end products (AGEs were detected on day 20. These AGEs were characterised by enhanced tryptophan fluorescence at 450 nm, exposure of heme, increase in intermolecular β-sheets, enhanced ThT fluorescence and red shift in CR absorbance. Comet assay revealed aggregates and AGEs to be genotoxic in nature. Scanning electron microscopy confirmed the amorphous structure of aggregates and branched fibrils of AGEs. The transformation of α-helix to β-sheet usually alters the normal protein to amyloidogenic resulting in a variety of protein conformational disorders such as diabetes, prion and Huntington's.

Correlation between Glycated Hemoglobin and Triglyceride Level in Type 2 Diabetes Mellitus.

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Naqvi, Syeda; Naveed, Shabnam; Ali, Zeeshan; Ahmad, Syed Masroor; Asadullah Khan, Raad; Raj, Honey; Shariff, Shoaib; Rupareliya, Chintan; Zahra, Fatima; Khan, Saba

2017-06-13

, physician-rated health status). After adjusting for relevant covariates, glycated hemoglobin was positively correlated with high triglyceride. Hence, HbA1c can be an indicator of triglyceride level and can be one of the predictors of cardiovascular risk factors in type 2 diabetes mellitus.

Vanillin restrains non-enzymatic glycation and aggregation of albumin by chemical chaperone like function.

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Awasthi, Saurabh; Saraswathi, N T

2016-06-01

Vanillin a major component of vanilla bean extract is commonly used a natural flavoring agent. Glycation is known to induce aggregation and fibrillation of globular proteins such as albumin, hemoglobin. Here we report the inhibitory potential of vanillin toward early and advanced glycation modification and amyloid like aggregation of albumin based on the determination of both early and advanced glycation and conformational changes in albumin using circular dichroism. Inhibition of aggregation and fibrillation of albumin was determined based on amyloid specific dyes i.e., Congo red and Thioflavin T and microscopic imaging. It was evident that vanillin restrains glycation of albumin and exhibits protective effect toward its native conformation. Copyright © 2016 Elsevier B.V. All rights reserved.

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

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Andreza Fabro de Bem

2006-06-01

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

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

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Balaji Bhavadharini

2017-01-01

Full Text Available 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.

Targeted quantification of N-1-(carboxymethyl) valine and N-1-(carboxyethyl) valine peptides of ?-hemoglobin for better diagnostics in diabetes

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Jagadeeshaprasad, Mashanipalya G.; Batkulwar, Kedar B.; Meshram, Nishita N.; Tiwari, Shalbha; Korwar, Arvind M.; Unnikrishnan, Ambika G.; Kulkarni, Mahesh J.

2016-01-01

Background N-1-(Deoxyfructosyl) valine (DFV) ?-hemoglobin (?-Hb), commonly referred as HbA1c, is widely used diagnostic marker in diabetes, believed to provide glycemic status of preceding 90?120?days. However, the turnover of hemoglobin is about 120?days, the DFV-?-Hb, an early and reversible glycation product eventually may undergo irreversible advanced glycation modifications such as carboxymethylation or carboxyethylation. Hence quantification of N-1-(carboxymethyl) valine (CMV) and N-1-(...

Association between blood glucose level derived using the oral glucose tolerance test and glycated hemoglobin level.

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Kim, Hyoung Joo; Kim, Young Geon; Park, Jin Soo; Ahn, Young Hwan; Ha, Kyoung Hwa; Kim, Dae Jung

2016-05-01

Glycated hemoglobin (HbA1c) is widely used as a marker of glycemic control. Translation of the HbA1c level to an average blood glucose level is useful because the latter figure is easily understood by patients. We studied the association between blood glucose levels revealed by the oral glucose tolerance test (OGTT) and HbA1c levels in a Korean population. A total of 1,000 subjects aged 30 to 64 years from the Cardiovascular and Metabolic Diseases Etiology Research Center cohort were included. Fasting glucose levels, post-load glucose levels at 30, 60, and 120 minutes into the OGTT, and HbA1c levels were measured. Linear regression of HbA1c with mean blood glucose levels derived using the OGTT revealed a significant correlation between these measures (predicted mean glucose [mg/dL] = 49.4 × HbA1c [%] - 149.6; R (2) = 0.54, p Glucose (ADAG) study and Diabetes Control and Complications Trial (DCCT) cohort. Discrepancies between our results and those of the ADAG study and DCCT cohort may be attributable to differences in the test methods used and the extent of insulin secretion. More studies are needed to evaluate the association between HbA1c and self monitoring blood glucose levels.

Multiwavelength pulse oximetry in the measurement of hemoglobin fractions

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Manzke, Bernd; Schwider, Johannes; Lutter, Norbert O.; Engelhardt, Kai; Stork, Wilhelm

1996-04-01

The two wavelength design of the majority of pulse oximeters assumes only two absorbing hemoglobin fractions, oxyhemoglobin (O2Hb), and reduced hemoglobin (HHb) irrespective of the presence of methemoglobin (MetHb) and carboxyhemoglobin (COHb). If MetHb or COHb is present, it contributes to the pulse-added absorbance signal and will be interpreted as either HHb or O2Hb or some combination of the two. In this paper we describe a noninvasive multi-wavelength pulse oximeter measuring O2Hb, HHb, MetHb, and COHb at a specified accuracy of 1.0%. The system was designed with respect to the results of numerical simulations. It consists of 9 laserdiodes (LDs) and 7 light emitting diodes (LEDs), a 16-bit analog-digital converter (ADC) and has a sampling rate of 16 kHz. The laser didoes and LEDs were coupled into multi-mode fibers and led with a liquid lightguide to the finger clip and then the photodiode. It also presents the results of a clinical study, including a setup with a quartz tungsten halogen lamp (with fiber output) and a diode array spectrometer, a standard pulse oximeter and two in-vitro oximeters (radiometer OSM3 and radiometer ABL 520) as references.

Glycated albumin as a marker of glycemia in diabetes and its vascular complications

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Maria Warwas

2015-05-01

Full Text Available Effective glycemic control is very important to prevent the onset and the progression of chronic complications in diabetic patients. It is known that glycation of various proteins is increased in diabetic patients compared with non-diabetics. Among these glycated proteins, glycated hemoglobin (HbA1c is commonly used as a gold standard index of glycemic control in the clinical setting. However, it can be unreliable in conditions affecting the lifespan of erythrocytes (120 days as well as in the clinical state in which glycemic control alleviates or deteriorates in a short period. By overcoming the shortcomings of HbA1c, glycated albumin (GA has gained interest as a useful index for an intermediate glycation period (2 weeks and pathogenic protein.After giving a brief overview of the key role of HbA1c as a long-term glycemic marker, this review focuses on (a glycation of human albumin and its main properties, (b methods of GA determination, (c the recent clinical status of GA as a glycemic index in diabetic patients and its association with vascular complications. Finally, conditions with a possible inaccurate GA level are also mentioned.

Inhibitory effect of Piper betle Linn. leaf extract on protein glycation--quantification and characterization of the antiglycation components.

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Bhattacherjee, Abhishek; Chakraborti, Abhay Sankar

2013-12-01

Piper betle Linn. is a Pan-Asiatic plant having several beneficial properties. Protein glycation and advanced glycation end products (AGEs) formation are associated with different pathophysiological conditions, including diabetes mellitus. Our study aims to find the effect of methanolic extract of P. betle leaves on in vitro protein glycation in bovine serum albumin (BSA)-glucose model. The extract inhibits glucose-induced glycation, thiol group modification and carbonyl formation in BSA in dose-dependent manner. It inhibits different stages of protein glycation, as demonstrated by using glycation models: hemoglobin-delta-gluconolactone (for early stage, Amadori product formation), BSA-methylglyoxal (for middle stage, formation of oxidative cleavage products) and BSA-glucose (for last stage, formation of AGEs) systems. Several phenolic compounds are isolated from the extract. Considering their relative amounts present in the extract, rutin appears to be the most active antiglycating agent. The extract of P. betle leaf may thus have beneficial effect in preventing protein glycation and associated complications in pathological conditions.

Determination of reference ranges for immature platelet and reticulocyte fractions and reticulocyte hemoglobin equivalent

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Iuri Vicente Camargo Morkis

Full Text Available ABSTRACT Introduction: The immature platelet and immature reticulocyte fractions represent the ratios of platelets and reticulocytes recently released into the circulation and thus with higher RNA content. They are considered early indicators of bone marrow recovery. Objective: The aim of this study was to determine the reference ranges for the immature platelet and reticulocyte fractions of hematologically normal individuals in a university hospital. Methods: Venous blood samples collected in ethylenediaminetetraacetic acid K3 were analyzed using a Sysmex XE-5000™ analyzer. Individuals with platelet and reticulocyte counts within the reference ranges, and a blood count within the laboratory's screening criteria were included. Individuals with clinical conditions that could affect hematological results were excluded. The immature platelet fraction, high, medium and low fluorescence reticulocyte fractions and reticulocyte hemoglobin equivalent were evaluated. The reference ranges were determined according to the recommendations of the International Federation of Clinical Chemistry. Results: One hundred and thirty-two outpatients were evaluated. The mean age was 44 years (range: 13-80 years, 72 (54.5% were women treated in a university hospital. The mean platelet count was 250.8 × 109/L and the mean reticulocyte count was 0.052 × 109/L. The following reference ranges were obtained: immature reticulocyte fraction 1.6-12.1%, the high, medium and low fluorescence reticulocyte fractions were 0.0-1.7%, 1.6-11.0% and 87.9-98.4%, respectively, the reticulocyte hemoglobin equivalent was 30.0-37.6% and immature platelet fraction was 0.8-5.6%. There was a statistically significant difference (p-value = 0.006 between genders in respect to the immature platelet fraction with 0.8-4.7% for females and 0.7-6.1% for males. The immature reticulocyte fraction was directly correlated with the reticulocyte count. Conclusion: Determining the reference range is

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

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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. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Hemoglobin

Science.gov (United States)

1993-03-08

affinity, which is less at low levels of hemoglobin saturation, increases markedly as fractional saturation increases. Thus, high affinity for 02 at... diphosphoglycerate (2,3-DPG), and carbon dioxide (Co 2). Since they are linked to 02 binding, they are called oxygen-linked effectors. The oxygen...hemoglobin molecule because of the negative charge of the ions. 2,3- Diphosphoglycerate is a molecule formed during the breakdown of sugar in normal human

Aspartic acid functions as carbonyl trapper to inhibit the formation of advanced glycation end products by chemical chaperone activity.

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Prasanna, Govindarajan; Saraswathi, N T

2016-05-01

Advanced glycation end products (AGEs) were implicated in pathology of numerous diseases. In this study, we present the bioactivity of aspartic acid (Asp) to inhibit the AGEs. Hemoglobin and bovine serum albumin (BSA) were glycated with glucose, fructose, and ribose in the presence and absence of Asp (100-200 μM). HbA1c inhibition was investigated using human blood and characterized by micro-column ion exchange chromatography. The effect of methyl glyoxal (MG) on hemoglobin and BSA was evaluated by fluorescence spectroscopy and gel electrophoresis. The effect of MG on red blood cells morphology was characterized by scanning electron micrographs. Molecular docking was performed on BSA with Asp. Asp is capable of inhibiting the formation of fluorescent AGEs by reacting with the reducing sugars. The presence of Asp as supplement in whole blood reduced the HbA1c% from 8.8 to 6.1. The presence of MG showed an increase in fluorescence and the presence of Asp inhibited the glycation thereby the fluorescence was quenched. MG also affected the electrophoretic mobility of hemoglobin and BSA by forming high molecular weight aggregates. Normal RBCs showed typical biconcave shape. MG modified RBCs showed twisted and elongated shape whereas the presence of ASP tends to protect RBC from twisting. Asp interacted with arginine residues of bovine serum albumin particularly ARG 194, ARG 198, and ARG 217 thereby stabilized the protein complex. We conclude that Asp has dual functions as a chemical chaperone to stabilize protein and as a dicarbonyl trapper, and thereby it can prevent the complications caused by glycation.

Correlation between Cholesterol, Triglycerides, Calculated, and Measured Lipoproteins: Whether Calculated Small Density Lipoprotein Fraction Predicts Cardiovascular Risks

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Sikandar Hayat Khan

2017-01-01

Full Text Available Background. Recent literature in lipidology has identified LDL-fractions to be more atherogenic. In this regard, small density LDL-cholesterol (sdLDLc has been considered to possess more atherogenicity than other LDL-fractions like large buoyant LDL-cholesterol (lbLDLc. Recently, Srisawasdi et al. have developed a method for calculating sdLDLc and lbLDLc based upon a regression equation. Using that in developing world may provide us with a valuable tool for ASCVD risk prediction. Objective. (1 To correlate directly measured and calculated lipid indices with insulin resistance, UACR, glycated hemoglobin, anthropometric indices, and blood pressure. (2 To evaluate these lipid parameters in subjects with or without metabolic syndrome, nephropathy, and hypertension and among various groups based upon glycated hemoglobin results. Design. Cross-sectional study. Place and Duration of Study. From Jan 2016 to 15 April 2017. Subjects and Methods. Finally enrolled subjects (male: 110, female: 122 were evaluated for differences in various lipid parameters, including measured LDL-cholesterol (mLDLc, HDLc and calculated LDL-cholesterol (cLDLc, non-HDLc, sdLDLC, lbLDLC, and their ratio among subjects with or without metabolic syndrome, nephropathy, glycation index, anthropometric indices, and hypertension. Results. Significant but weak correlation was mainly observed between anthropometric indices, insulin resistance, blood pressure, and nephropathy for non-HDLc, sdLDLc, and sdLDLc/lbLDLc. Generally lipid indices were higher among subjects with metabolic syndrome [{sdLDLc: 0.92 + 0.33 versus 0.70 + 0.29 (p 7.0%. Subjects having nephropathy (UACR > 2.4 mg/g had higher concentration of non-HDLc levels in comparison to sdLDLc [{non-HDLc: 3.68 + 0.59 versus 3.36 + 0.43} (p=0.007, {sdLDLc: 0.83 + 0.27 versus 0.75 + 0.35 (p=NS}]. Conclusion. Lipid markers including cLDLc and mLDLc are less associated with traditional ASCVD markers than non-HDLc, sdLDLc, and sd

Glycated Hemoglobin Levels in Patients with Decompensated Cirrhosis

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Jeffrey Nadelson

2016-01-01

Full Text Available 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 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.

Accumulation of glycation products in. cap alpha. -H pig lens crystallin and its bearing to diabetic cataract genesis

Energy Technology Data Exchange (ETDEWEB)

Vidal, P; Cabezas-Cerrato, J

1988-01-01

The incorporation of /sup 11/C-glucose in native pig crystalline by in vitro incubation was found, after subsequent dialysis, to affect all 5 classes of crystallin separated by Sepharose CL-6B column chromatography. Though the radioactivity of the ..cap alpha..-H fraction was three times greater than that of any of the others, autoradiographs of SDS-PAGE gels showed /sup 11/C-glucose adducts to be present in all soluble protein subunits, without there being any evidence of preferential glycation of the ..cap alpha..-H subunits. The concentration of stable glycation products in the ..cap alpha..-H chromatographic fraction of soluble crystallins is suggested to be due the addition of glycated material to this fraction as result of glycation-induced hyperaggregation, and not because the ..cap alpha..-H subunits were especially susceptible to glycation.

A novel glycated hemoglobin A1c-lowering traditional Chinese medicinal formula, identified by translational medicine study.

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Hsin-Yi Lo

Full Text Available 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.

Ebselen exhibits glycation-inhibiting properties and protects against osmotic fragility of human erythrocytes in vitro.

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Soares, Julio C M; Folmer, Vanderlei; Da Rocha, João B T; Nogueira, Cristina W

2014-05-01

Diabetic status is associated with an increase on oxidative stress markers in humans and animal models. We have investigated the in vitro effects of high concentrations of glucose on the profile of oxidative stress and osmotic fragility of blood from control and diabetic patients; we considered whether its antioxidant properties could afford some protection against glucose-induced osmotic fragility, and whether ebselen could act as an inhibitor of hemoglobin glycation. Raising blood glucose to 5-100 mmol/L resulted in a concentration-dependent increase of glycated hemoglobin (HbA1c; P Ebselen significantly reduced the glucose-induced increase in osmotic fragility and inhibited HbA1c formation (P < 0.0001). These results indicate that blood from patients with uncontrolled diabetes are more sensitive to osmotic shock than from patients with controlled diabetes and control subjects in relation to increased production of free radicals in vivo. © 2014 International Federation for Cell Biology.

Evidence for Consistency of the Glycation Gap in Diabetes

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Nayak, Ananth U.; Holland, Martin R.; Macdonald, David R.; Nevill, Alan; Singh, Baldev M.

2011-01-01

OBJECTIVE Discordance between HbA1c and fructosamine estimations in the assessment of glycemia is often encountered. A number of mechanisms might explain such discordance, but whether it is consistent is uncertain. This study aims to coanalyze paired glycosylated hemoglobin (HbA1c)-fructosamine estimations by using fructosamine to determine a predicted HbA1c, to calculate a glycation gap (G-gap) and to determine whether the G-gap is consistent over time. RESEARCH DESIGN AND METHODS We include...

Interaction of thyroid hormone and hemoglobin: nature of the interaction and effect of hemoglobin on thyroid hormone radioimmunoassay

International Nuclear Information System (INIS)

Davis, P.J.; Yoshida, K.; Schoenl, M.

1980-01-01

Gel filtration of human erythrocyte (RBC) lysate incubated with labeled thyroxine (Tu) or triiodothyronine (Tt) revealed co-elution of a major iodothyronine-binding fraction (R-2) and hemoglobin. Solutions of purified human hemoglobin and Tt also showed co-elution of hormone and hemoglobin. Because hematin and protoporphyrin were shown to bind labeled Tt, the oxygen-binding site on hemoglobin was excluded as the site of iodothyronine-hemoglobin interaction. Analysis of hormone binding by heme and globin moieties showed Tt binding to be limited to the heme fraction. Addition of excess unlabeled Tt to hemoglobin or heme incubated with labeled Tt indicated 75% to 90% of hormone binding was poorly dissociable. These observations suggested that the presence of hemoglobin in RBC lysate or in serum could influence the measurement of Tu and Tt by specific radioimmunoassay (RIA). Subsequent studies of the addition to serum of human hemoglobin revealed a significant reduction in Tt and Tu detectable by RIA in the presence of this protein. The effect was influenced by the concentration of hemoglobin and by duration and temperature of incubations of hemoglobin and serum prior to RIA

Association Between Neighborhood Supermarket Presence and Glycated Hemoglobin Levels Among Patients With Type 2 Diabetes Mellitus.

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Zhang, Y Tara; Mujahid, Mahasin S; Laraia, Barbara A; Warton, E Margaret; Blanchard, Samuel D; Moffet, Howard H; Downing, Janelle; Karter, Andrew J

2017-06-15

We estimated associations between neighborhood supermarket gain or loss and glycemic control (assessed by glycated hemoglobin (HbA1c) values) in patients from the Kaiser Permanente Northern California Diabetes Registry (n = 434,806 person-years; 2007-2010). Annual clinical measures were linked to metrics from a geographic information system for each patient's address of longest residence. We estimated the association between change in supermarket presence (gain, loss, or no change) and change in HbA1c value, adjusting for individual- and area-level attributes and according to baseline glycemic control (near normal, Supermarket loss was associated with worse HbA1c trajectories for those with good, moderate, and poor glycemic control at baseline, while supermarket gain was associated with marginally better HbA1c outcomes only among patients with near normal HbA1c values at baseline. Patients with the poorest baseline HbA1c values (≥9.0%) had the worst associated changes in glycemic control following either supermarket loss or gain. Differences were not clinically meaningful relative to no change in supermarket presence. For patients with type 2 diabetes mellitus, gaining neighborhood supermarket presence did not benefit glycemic control in a substantive way. The significance of supermarket changes on health depends on a complex interaction of resident, neighborhood, and store characteristics. © The Author 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Effect of chromium supplementation on glycated hemoglobin and fasting plasma glucose in patients with diabetes mellitus.

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Yin, Raynold V; Phung, Olivia J

2015-02-13

Chromium (Cr) is a trace element involved in glucose homeostasis. We aim to evaluate and quantify the effects of Cr supplementation on A1C and FPG in patients with T2DM. A systematic literature search of Pubmed, EMBASE and the Cochrane Library (from database inception to 11/2014) with no language restrictions sought RCTs or cohort studies evaluating Cr supplementation in T2DM vs control and reporting either change in glycated hemoglobin (A1C) or fasting plasma glucose (FPG). Meta-analysis was conducted on each subtype of Cr supplement separately, and was analyzed by random effects model to yield the weighted mean differences (WMD) and 95% confidence intervals (CIs). Heterogeneity was assessed by using the I(2) statistic. A total of 14 RCTs (n=875 participants, mean age range: 30 to 83 years old, 8 to 24 weeks of follow-up) were identified (Cr chloride: n=3 study, Cr picolinate: n=5 study, brewer's yeast: n=4 study and Cr yeast: n=3 study). Compared with placebo, Cr yeast, brewer's yeast and Cr picolinate did not show statistically significant effects on A1C. Furthermore, compared to control, Cr chloride, Cr yeast and Cr picolinate showed no effect on FPG, however, brewer's yeast showed a statistically significant decrease in FPG -19.23 mg/dL (95% CI=-35.30 to -3.16, I(2)=21%, n=137). Cr supplementation with brewer's yeast may provide marginal benefits in lowering FPG in patients with T2DM compared to placebo however it did not have any effect on A1C.

Glycated hemoglobin correlates with arterial stiffness and endothelial dysfunction in patients with resistant hypertension and uncontrolled diabetes mellitus.

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Moreno, Beatriz; de Faria, Ana Paula; Ritter, Alessandra Mileni Versuti; Yugar, Lara Buonalumi Tacito; Ferreira-Melo, Silvia Elaine; Amorim, Rivadavio; Modolo, Rodrigo; Fattori, André; Yugar-Toledo, Juan Carlos; Coca, Antonio; Moreno, Heitor

2018-05-01

This study aimed to evaluate the effects of glycated hemoglobin (HbA 1c ) on flow-mediated dilation, intima-media thickness, pulse wave velocity, and left ventricular mass index in patients with resistant hypertension (RHTN) comparing RHTN-controlled diabetes mellitus and RHTN-uncontrolled type 2 diabetes mellitus. Two groups were formed: HbA 1c diabetes mellitus: n = 98) and HbA 1c ≥7.0% (RHTN-uncontrolled diabetes mellitus: n = 122). Intima-media thickness and flow-mediated dilation were measured by high-resolution ultrasound, left ventricular mass index by echocardiography, and arterial stiffness by carotid-femoral pulse wave velocity. No differences in blood pressure levels were found between the groups but body mass index was higher in patients with RHTN-uncontrolled diabetes mellitus. Endothelial dysfunction and arterial stiffness were worse in patients with RHTN-uncontrolled diabetes mellitus. Intima-media thickness and left ventricular mass index measurements were similar between the groups. After adjustments, multiple linear regression analyses showed that HbA 1c was an independent predictor of flow-mediated dilation and pulse wave velocity in all patients with RHTN. In conclusion, HbA 1c may predict the grade of arterial stiffness and endothelial dysfunction in patients with RHTN, and superimposed uncontrolled diabetes mellitus implicates further impairment of vascular function. ©2018 Wiley Periodicals, Inc.

Lyophilized bovine hemoglobin as a possible reference material for the determination of hemoglobin derivatives in human blood

NARCIS (Netherlands)

Maas, BHA; Buursma, A; Ernst, RAJ; Maas, AHJ; Zijlstra, WG

We investigated the suitability of a lyophilized bovine hemoglobin (LBH) preparation containing various fractions of oxyhemoglobin (O(2)Hb), carboxyhemoglobin (COHb), and methemoglobin (MetHb) for quality assessment in multicomponent analysis (MCA) of hemoglobin derivatives. It was demonstrated that

Lyophilized bovine hemoglobin as a possible reference material for the determination of hemoglobin derivatives in human blood

NARCIS (Netherlands)

Maas, BHA; Buursma, A; Ernst, RAJ; Maas, AHJ; Zijlstra, WG

1998-01-01

We investigated the suitability of a lyophilized bovine hemoglobin (LBH) preparation containing various fractions of oxyhemoglobin (O(2)Hb), carboxyhemoglobin (COHb), and methemoglobin (MetHb) for quality assessment in multicomponent analysis (MCA) of hemoglobin derivatives. It was demonstrated that

Assessment of nonenzymatic glycation in protein by FTIR spectroscopy

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Otero de Joshi, Virginia; Joshi, Narahari V.; Gil, Herminia; Velasquez, William; Contreras, Silvia; Marquez, Glevis

1999-04-01

Detection of nonenzymatic glycated proteins is a very significant feature in diabetes, aging and related diseases, therefore we have carried out an FTIR spectroscopic study for glycated and native proteins such as (gamma) -globulin, human serum albumin. For this purpose, commercially available proteins were glycated by a usual procedure and their FTIR spectra were recorded together with that of the native ones. In order to follow the changes in time, (gamma) -globulin was glycated during 1, 2, 3, 5 and 8 weeks and their spectra were recorded. Direct verification was obtained by examining a model unit where the -NH2 group was attached to glucose. The spectrum shows a strong peak at 3500 cm-1 confirming the observed variation in time dependent spectra. The general features of the spectra are very similar and there was no additional structure or change in the peaks. This is understandable as not all the lysine residues are glycated, only a small fraction. Glucose is attached to the (epsilon) -amino group of lysine to form Amadori products, and therefore, the vibrational modes corresponding to the (epsilon) -NH2 unit of lysine are expected to be altered. This region exactly lies in the Amide I region of protein structure. Careful investigation of this part, indeed, shows a complex structure originated from alternations of -NH2 group. Thus, the present investigation indicates that an optical approach could be a rapid and effective method to identify the nonenzymatic glycation process.

Comments on Meo et al. 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. Int. J. Environ. Res. Public Health, 2015, 12, 14519–14528

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Seyed Alireza Mortazavi

2016-02-01

Full Text Available With great interest and enthusiasm, we have read the article by Meo et al. entitled “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” that is published in the latest issue of the International Journal of Environmental Research and Public Health [1].[...

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

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Lubia Velázquez-López

2016-01-01

Full Text Available 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.

Identification of a haptoglobin-hemoglobin complex in the Alaskan Least Cisco (Coregonus sardinella).

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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.

Correlation between Total Solar Irradiance and Glycated Hemoglobin 2 to 3 Months Later in Patients with Diabetes: A Big-Data Analysis.

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Kinchiku, Shigesumi; Kotani, Kazuhiko; Maruguchi, Yukiko; Aikou, Anna; Uenomachi, Hitoshi; Kajiya, Shouko

2016-12-01

Much attention has been paid recently to a relationship between glucose metabolism and weather. This study investigated the temporal correlation between total solar irradiance (TSI) and glycated hemoglobin (A1C) values in patients with diabetes. In 1531 patients with diabetes who received follow-up care between 2009 and 2013 (type 1 diabetes, 123 patients; type 2 diabetes, 1408 patients; male 53.6%; mean age, 61.2 years), A1C levels were measured a total of 58,830 times. The correlation between mean monthly TSI and mean A1C values from 1 to 4 months later was then examined. The mean values for TSI and A1C throughout the entire study period were 13.7 MJ/m 2 and 7.7%, respectively. The correlation coefficient between TSI and mean monthly A1C values at 1 to 4 months was -0.516, -0.734, -0.726 and -0.475, respectively (all p<0.001). There was a highly negative correlation between TSI and mean A1C values 2 to 3 months later in this population; thus, this fact may need to be considered when using A1C levels as a glycemic control index in patients with diabetes. Further studies are warranted. Copyright © 2016 Canadian Diabetes Association. Published by Elsevier Inc. All rights reserved.

Biphasic oxidation of oxy-hemoglobin in bloodstains

NARCIS (Netherlands)

Bremmer, Rolf H.; de Bruin, Daniel M.; de Joode, Maarten; Buma, Wybren Jan; van Leeuwen, Ton G.; Aalders, Maurice C. G.

2011-01-01

In forensic science, age determination of bloodstains can be crucial in reconstructing crimes. Upon exiting the body, bloodstains transit from bright red to dark brown, which is attributed to oxidation of oxy-hemoglobin (HbO(2)) to met-hemoglobin (met-Hb) and hemichrome (HC). The fractions of

Biphasic Oxidation of Oxy-Hemoglobin in Bloodstains

NARCIS (Netherlands)

Bremmer, R.H.; de Bruin, D.M.; de Joode, M.; Buma, W.J.; van Leeuwen, T.G.; Aalders, M.C.G.

2011-01-01

Background In forensic science, age determination of bloodstains can be crucial in reconstructing crimes. Upon exiting the body, bloodstains transit from bright red to dark brown, which is attributed to oxidation of oxy-hemoglobin (HbO2) to met-hemoglobin (met-Hb) and hemichrome (HC). The fractions

Glycated Lysine Residues: A Marker for Non-Enzymatic Protein Glycation in Age-Related Diseases

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Nadeem A. Ansari

2011-01-01

Full Text Available Nonenzymatic glycosylation or glycation of macromolecules, especially proteins leading to their oxidation, play an important role in diseases. Glycation of proteins primarily results in the formation of an early stage and stable Amadori-lysine product which undergo further irreversible chemical reactions to form advanced glycation endproducts (AGEs. This review focuses these products in lysine rich proteins such as collagen and human serum albumin for their role in aging and age-related diseases. Antigenic characteristics of glycated lysine residues in proteins together with the presence of serum autoantibodies to the glycated lysine products and lysine-rich proteins in diabetes and arthritis patients indicates that these modified lysine residues may be a novel biomarker for protein glycation in aging and age-related diseases.

Effect of cocoyam (Colocasia esculenta), unripe plantain (Musa paradisiaca) or their combination on glycated hemoglobin, lipogenic enzymes, and lipid metabolism of streptozotocin-induced diabetic rats.

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Eleazu, Chinedum Ogbonnaya; Eleazu, Kate Chinedum; Iroaganachi, Mercy Amarachi

2016-01-01

The possibility of combining unripe plantain [Musa paradisiacae Linn (Plantaginaceae)] and cocoyam [Colocassia esculenta Linn (Araceae)] in the management of diabetes has not been investigated. The objective of this study is to evaluate the antihyperglycemic and antihyperlipidemic actions of unripe plantain and cocoyam. Diabetes was induced in rats by intraperitoneal injection of streptozotocin (STZ) (65 mg/kg body weight). Twelve days after STZ induction, respective groups of diabetic rats were fed cocoyam (810 g/kg), unripe plantain (810 g/kg), and unripe plantain + cocoyam (405:405 g/kg) for 28 d. Body weights, feed intake, biochemical parameters, namely serum glucose, total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), very low-density lipoprotein (VLDL), atherogenic index, coronary risk index, triacylglycerol, glycated hemoglobin (HbA1C), hepatic isocitrate dehydrogenase, malic enzyme, and glucose-6-phosphate dehydrogenase of the rats and phytochemical composition of the test and standard rat feeds were measured. Cocoyam or unripe plantain alone significantly (p 0.05) at the end of experimentation and the feed samples contained considerable amounts of saponins, alkaloids, flavonoids, and tannins. Cocoyam or unripe plantain alone showed better antihyperglycemic and anihyperlipidemic action than their combination.

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

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Elysa Nur Safrida

2017-04-01

Full Text Available Background Central obesity has been associated with a high risk of insulin resistance. Waist circumference and waist-to-height ratio are anthropometric indices for determining central obesity and have been associated with increased blood pressure, cholesterol, and insulin levels. In adults, fat distribution around the waist is a valid predictor of glycated hemoglobin (HbA1clevels, and is currently recommended by experts as a diagnostic tool for diabetes. Central obesity measurement has advantages over fasting blood glucose and oral glucose tolerance tests, as it is simple and inexpensive to perform. Objective To assess for correlations between HbA1c level and waist circumference as well as waist-to-height ratio and to assess factors potentially associated with HbA1c levels in overweight and obese adolescents. Methods This cross-sectional study was done in four junior high schools in Yogyakarta, which were obtained by cluster sampling. Overweight and obese students who were generally healthy were included in the study. Subjects underwent waist circumference and waist-to-height ratio measurements, as well as blood tests for HbA1clevels. Results Sixty-seven children participated in the study, with 48 girls (71.6% and 19 boys (28.4%. Waist circumference and HbA1c levels were not significantly associated (r=0.178; P=0.15. However, waist-to-height ratio and HbA1c levels had a weak positive correlation (r=0.21; P=0.04. Linear regression analysis revealed that waist-to-height ratio had a significant association with HbA1c level (P=0.02, but age, sex, and nutritional status did not. Conclusion Waist-to-height ratio is correlated with HbA1c levels in overweight and obese adolescents.

HbA1c levels in individuals heterozygous for hemoglobin variants.

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

2017-04-01

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

Relationship of Glucose Variability With Glycated Hemoglobin and Daily Mean Glucose: A Post Hoc Analysis of Data From 5 Phase 3 Studies.

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Luo, Junxiang; Qu, Yongming; Zhang, Qianyi; Chang, Annette M; Jacober, Scott J

2018-03-01

The association of glucose variability (GV) with other glycemic measures is emerging as a topic of interest. The aim of this analysis is to study the correlation between GV and measures of glycemic control, such as glycated hemoglobin (HbA1c) and daily mean glucose (DMG). Data from 5 phase 3 trials were pooled into 3 analysis groups: type 2 diabetes (T2D) treated with basal insulin only, T2D treated with basal-bolus therapy, and type 1 diabetes (T1D). A generalized boosted model was used post hoc to assess the relationship of the following variables with glycemic control parameters (HbA1c and DMG): within-day GV, between-day GV (calculated using self-monitored blood glucose and fasting blood glucose [FBG]), hypoglycemia rate, and certain baseline characteristics. Within-day GV (calculated using standard deviation [SD]) was found to have a significant influence on endpoints HbA1c and DMG in all 3 patient groups. Between-day GV from FBG (calculated using SD), within-day GV (calculated using coefficient of variation), and hypoglycemia rate were found to significantly influence the endpoint HbA1c in the T2D basal-only group. Lower within-day GV was significantly associated with improvement in DMG and HbA1c. This finding suggests that GV could be a marker in the early phases of new antihyperglycemic therapy development for predicting clinical outcomes in terms of HbA1c and DMG.

Ex vivo instability of glycated albumin: A role for autoxidative glycation.

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Jeffs, Joshua W; Ferdosi, Shadi; Yassine, Hussein N; Borges, Chad R

2017-09-01

Ex vivo protein modifications occur within plasma and serum (P/S) samples due to prolonged exposure to the thawed state-which includes temperatures above -30 °C. Herein, the ex vivo glycation of human serum albumin from healthy and diabetic subjects was monitored in P/S samples stored for hours to months at -80 °C, -20 °C, and room temperature, as well as in samples subjected to multiple freeze-thaw cycles, incubated at different surface area-to-volume ratios or under different atmospheric compositions. A simple dilute-and-shoot method utilizing trap-and-elute LC-ESI-MS was employed to determine the relative abundances of the glycated forms of albumin-including forms of albumin bearing more than one glucose molecule. Significant increases in glycated albumin were found to occur within hours at room temperature, and within days at -20 °C. These increases continued over a period of 1-2 weeks at room temperature and over 200 days at -20 °C, ultimately resulting in a doubling of glycated albumin in both healthy and diabetic patients. It was also shown that samples stored at lower surface area-to-volume ratios or incubated under a nitrogen atmosphere experienced less rapid glucose adduction of albumin-suggesting a role for oxidative glycation in the ex vivo glycation of albumin. Copyright © 2017 Elsevier Inc. All rights reserved.

Advanced glycation endproducts form during ovalbumin digestion in the presence of fructose: Inhibition by chlorogenic acid.

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Bains, Yasmin; Gugliucci, Alejandro; Caccavello, Russell

2017-07-01

One mechanism by which fructose could exert deleterious effects is through intestinal formation and absorption of pro-inflammatory advanced glycation endproducts via the Maillard reaction. We employed simulated stomach and duodenum digestion of ovalbumin (OVA) to test the hypothesis that advanced glycation endproducts (AGEs) are formed by fructose during simulated digestion of a ubiquitous food protein under model physiological conditions. OVA was subjected to simulated gastric and intestinal digestion using standard models, in presence of fructose or glucose (0-100mM). Peptide fractions were analyzed by fluorescence spectroscopy and intensity at Excitation: λ370nm, Emission: λ 440nm. AGE adducts formed between fructose and OVA, evidenced by the peptide fractions (fructose-AGE formation on a ubiquitous dietary protein under model physiological conditions. Our study also suggests ways to decrease the damage: enteral fructose-AGE formation may be partially inhibited by co-intake of beverages, fruits and vegetables with concentrations of phenolics high enough to serve as anti-glycation agents. Copyright © 2017 Elsevier B.V. All rights reserved.

Prognostic significance of hemoglobin level in patients with congestive heart failure and normal ejection fraction.

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Varadarajan, Padmini; Gandhi, Siddharth; Sharma, Sanjay; Umakanthan, Branavan; Pai, Ramdas G

2006-10-01

Previous studies have shown low hemoglobin (Hb) to have an adverse effect on survival in patients with congestive heart failure (CHF) and reduced left ventricular (LV) ejection fraction (EF); but its effect on survival in patients with CHF and normal EF is not known. This study sought to determine whether low Hb has an effect on survival in patients with both CHF and normal EF. Detailed chart reviews were performed by medical residents on 2,246 patients (48% with normal EF) with a discharge diagnosis of CHF in a large tertiary care hospital from 1990 to 1999. The CHF diagnosis was validated using the Framingham criteria. Mortality data were obtained from the National Death Index. Survival analysis was performed using Kaplan-Meier and Cox regression models. By Kaplan-Meier analysis, low Hb (< 12 gm/dl) compared with normal hemoglobin was associated with a lower 5-year survival in patients with CHF and both normal (38 vs. 50%, p = 0.0008) and reduced (35 vs. 48%, p = 0.0009) EF. Using the Cox regression model, low Hb was an independent predictor of mortality after adjusting for age, gender, renal dysfunction, diabetes mellitus, hypertension, and EF in both groups of patients. Low Hb has an independent adverse effect on survival in patients with CHF and both normal and reduced EF in both groups of patients.

Glycated Lysine Residues: A Marker for Non-Enzymatic Protein Glycation in Age-Related Diseases

OpenAIRE

Ansari, Nadeem A.; Moinuddin,; Ali, Rashid

2011-01-01

Nonenzymatic glycosylation or glycation of macromolecules, especially proteins leading to their oxidation, play an important role in diseases. Glycation of proteins primarily results in the formation of an early stage and stable Amadori-lysine product which undergo further irreversible chemical reactions to form advanced glycation endproducts (AGEs). This review focuses these products in lysine rich proteins such as collagen and human serum albumin for their role in aging and age-related dise...

Lack of Correlation of the Serum 25(OH Vitamin D Levels with the Glycated Hemoglobin A1c and the Lipid Profile in Type 2 Diabetes Patients on Oral Antidiabetic Drugs – Preliminary Data

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Bakalov D.

2014-12-01

Full Text Available Data from different studies correlating the serum 25(OHD levels with the metabolic and glycemic parameters in type 2 diabetes patients are still varying. The objective if this study was to describe the correlation between serum 25(OHD levels and some metabolic parameters in Bulgarian type 2 diabetes patients on oral antidiabetic drugs. One hundred type 2 diabetes patients participated - 56 men and 44 women. The mean age and diabetes duration of the women was 59.0 and 9.8 years, of the men - 58.0 and 7.7 years respectively. Complete patient history was taken and physical examination was performed (body weight and height, waist circumference. Body composition was measured on a leg-to-leg body impedance analyzer (TBF-215, Tanita Corp., Tokyo, Japan. Serum levels of vitamin D were measured by electro-hemi-luminescent detection as 25-(ОН D Total (ECLIA, Elecsys 2010, Roche Diagnostics, Switzerland. Glycated hemoglobin A1c was measured on a NycoCard reader (Alere™. Total, HDL-cholesterol (direct and triglycerides were analyzed on a Cobas Integra 400+ analyzer. Correlation analysis was performed on a SPSS 13.0 for Windows platform and included 10 curves. The data were first analyzed for the group as a whole and then separately for men and women as well as in the different vitamin D tertiles. The mean serum 25-OH-vitamin D levels were 23.8 ± 12.1 nmol/l in women and 33.3 ± 20.0 nmol/l in men. We were unable to find any statistically significant correlation between serum 25(OH vitaminand the serum lipids (cholesterol profile and triglycerides. On the contrary, there was a weak correlation with the glycated hemoglobin A1c (cubic model, R2 = 0.178, p = 0.05 and the BMI (inverse model, R2 = 0.101, p = 0.038. The sub-analyses (men versus women or according to tertiles of vitamin D did not produce any additional information. The influence of vitamin D on the parameters of the metabolic control in type 2 diabetes is very weak on an individual level. It

Betanin reduces the accumulation and cross-links of collagen in high-fructose-fed rat heart through inhibiting non-enzymatic glycation.

Science.gov (United States)

Han, Junyan; Tan, Chang; Wang, Yiheng; Yang, Shaobin; Tan, Dehong

2015-02-05

We attempted to determine whether betanin (from natural pigments) that has antioxidant properties would be protective against fructose-induced diabetic cardiac fibrosis in Sprague-Dawley rats. Fructose water solution (30%) was accessed freely, and betanin (25 and 100 mg/kg/d) was administered by intra-gastric gavage continuously for 60 d. Rats were sacrificed after overnight fast. The rat blood and left ventricle were collected. In vitro antiglycation assay in bovine serum albumin/fructose system was also performed. In rats treated only with fructose, levels of plasma markers: glucose, insulin, HOMA and glycated hemoglobin rised, left ventricle collagen accumulated and cross-linked, profibrotic factor-transforming growth factor (TGF)-β1 and connective tissue growth factor (CTGF) protein expression increased, and soluble collagen decreased, compared with those in normal rats, showing fructose induces diabetic cardiac fibrosis. Treatment with betanin antagonized the changes of these parameters, demonstrating the antifibrotic role of betanin in the selected diabetic models. In further mechanistic study, betanin decreased protein glycation indicated by the decreased levels of protein glycation reactive intermediate (methylglyoxal), advanced glycation end product (N(ε)-(carboxymethyl) lysine) and receptors for advanced glycation end products (AGEs), antagonized oxidative stress and nuclear factor-κB activation elicited by fructose feeding, suggesting inhibition of glycation, oxidative stress and nuclear factor-κB activation may be involved in the antifibrotic mechanisms. Betanin also showed anitglycative effect in BSA/fructose system, which supported that anitglycation was involved in betanin's protective roles in vivo. Taken together, the potential for using betanin as an auxillary therapy for diabetic cardiomyopathy deserves to be explored further. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Oxygen Measurements in Liposome Encapsulated Hemoglobin

Science.gov (United States)

Phiri, Joshua Benjamin

Liposome encapsulated hemoglobins (LEH's) are of current interest as blood substitutes. An analytical methodology for rapid non-invasive measurements of oxygen in artificial oxygen carriers is examined. High resolution optical absorption spectra are calculated by means of a one dimensional diffusion approximation. The encapsulated hemoglobin is prepared from fresh defibrinated bovine blood. Liposomes are prepared from hydrogenated soy phosphatidylcholine (HSPC), cholesterol and dicetylphosphate using a bath sonication method. An integrating sphere spectrophotometer is employed for diffuse optics measurements. Data is collected using an automated data acquisition system employing lock-in -amplifiers. The concentrations of hemoglobin derivatives are evaluated from the corresponding extinction coefficients using a numerical technique of singular value decomposition, and verification of the results is done using Monte Carlo simulations. In situ measurements are required for the determination of hemoglobin derivatives because most encapsulation methods invariably lead to the formation of methemoglobin, a nonfunctional form of hemoglobin. The methods employed in this work lead to high resolution absorption spectra of oxyhemoglobin and other derivatives in red blood cells and liposome encapsulated hemoglobin (LEH). The analysis using singular value decomposition method offers a quantitative means of calculating the fractions of oxyhemoglobin and other hemoglobin derivatives in LEH samples. The analytical methods developed in this work will become even more useful when production of LEH as a blood substitute is scaled up to large volumes.

Relationship between retinopathy in type 2 diabetics and glycated hemoglobin%糖尿病视网膜病变与糖化血红蛋白的关系

Institute of Scientific and Technical Information of China (English)

马金力; 朱成义

2011-01-01

探讨糖化血红蛋白（glycated hemoglobin,HbA1c）与2型糖尿病性视网膜病变（diabetic retinopathy,DR）的关系.方法300例2型糖尿病患者,根据其有无糖尿病视网膜病变及病变程度分为3组:正常视网膜组(non-diabetic retinopathy group,NDR)、非增殖型视网膜病变组(nonproliferative diabetic retinopathy group,NPDR)和增殖型视网膜病变组(proliferative diabetic retinopathy group,PDR),同时测定患者HbA1c浓度,并对相关因素如年龄、性别、病程、血压、糖尿病家族史等进行统计分析.结果NDR组、NPDR组和PDR组的HbAlc浓度差异有统计学意义(P＜0.05).结论HbA1c可作为监测DR发生和发展的重要指标之一.

Relationship between pulmonary function and elevated glycated hemoglobin levels in health checkups: A cross-sectional observational study in Japanese participants

Directory of Open Access Journals (Sweden)

Saigo Baba

2017-11-01

Full Text Available Background: Insulin resistance has been associated with cytokines, including interleukin-6 and tumor necrosis factor alpha soluble receptor, both of which are elevated in chronic obstructive pulmonary disease (COPD. Few studies have investigated the relationship between pulmonary function tests using spirometry (PFT and fasting plasma glucose (FPG or glycated hemoglobin (HbA1c levels in Japanese participants. The purpose of this study was to clarify the relationship between PFT in Japanese people who had health checkups and their FPG or HbA1c levels. In the context of preventative medicine, we intend to connect early detection of COPD to an index of blood sugar. Methods: From August 2013 through March 2014, 1019 participants underwent health checkups. PFT, FPG, and HbA1c measurements were conducted. HbA1c levels were measured according to National Glycohemoglobin Standardization Program guidelines. Results: Participants with FPG ≥100 mg/dL and HbA1c ≥5.6% showed a significantly lower forced expiratory volume in 1 s:forced vital capacity ratio (FEV1/FVC compared to participants with lower FPG and Hb1Ac levels. Prevalence of FEV1/FVC values <70% in PFT differed significantly depending on sex, age, body mass index, FPG, HbA1c, and smoking habits. Age (≥60 years, HbA1c (≥5.6%, and current or former smoking were associated with FEV1/FVC values <70%. Conclusion: In Japan, HbA1c levels were higher in participants with FEV1/FVC values <70% in PFT than in those with FEV1/FVC ≥70%. In preventive medicine, PFT by spirometry should be performed in elderly participants with elevated HbA1c levels who are current or former smokers.

Combined use of fasting plasma glucose and glycated hemoglobin A1c in a stepwise fashion to detect undiagnosed diabetes mellitus.

Science.gov (United States)

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.

Association of diabetes-related distress, depression, medication adherence, and health-related quality of life with glycated hemoglobin, blood pressure, and lipids in adult patients with type 2 diabetes: a cross-sectional study

Directory of Open Access Journals (Sweden)

Chew BH

2015-04-01

Full Text Available Boon-How Chew,1 Mohd-Sidik Sherina,2 Noor-Hasliza Hassan3 1Department of Family Medicine, 2Department of Psychiatry, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang; 3Klinik Kesihatan Dengkil, Jalan Dengkil, Malaysia Abstract: This study examined the associations of diabetes-related distress (DRD, depressive symptoms, health-related quality of life (HRQoL, and medication adherence with glycemia, blood pressure (BP, and lipid biomarkers in adults with type 2 diabetes mellitus (T2D. This cross-sectional study was conducted in three Malaysian public health clinics in 2012–2013, recruited adult patients (aged ≥30 years with T2D who had been diagnosed for more than one year, were on active follow-up, and had recent blood test results. Univariable and multivariable analyses were performed to identify significant associated factors for glycated hemoglobin (HbA1c BP, and lipids. The response rate was 93.1% (700/752. The majority were females (52.8%, Malay (52.4%, and married (78.7%. DRD correlated with systolic BP (r= -0.16; depressive symptoms correlated with low-density lipoprotein cholesterol (r=0.12 and total cholesterol (r=0.13; medication adherence correlated with HbA1c (r= -0.14 and low-density lipoprotein cholesterol (r= -0.11; and HRQoL correlated with casual blood glucose (r= -0.11, high-density lipoprotein cholesterol (r= -0.13, and total cholesterol (r= -0.08. Multivariable analyses showed that HRQoL was significantly associated with casual blood glucose (adjusted B= -0.06, P=0.024; DRD was associated with systolic BP (adjusted B= -0.08, P=0.066; depressive symptoms were associated with low-density lipoprotein cholesterol (adjusted B=0.02, P=0.061, and medication adherence was associated with HbA1c (adjusted B= -0.11, P=0.082 and total cholesterol (adjusted B= -0.06, P=0.086. There were significant and distinctive associations of DRD, depressive symptoms, HRQoL, and medication adherence with

[Relationship among glycated compounds, superoxide dismutase activities, and other related analytes in diabetic patients classified by ages].

Science.gov (United States)

Maehata, E; Shimomura, H; Kiyose, H; Hayashi, A; Sakagishi, Y

1991-07-01

Among several glycated compounds (GC) which are based on Maillard reaction, glycated hemoglobin (HbA1c) and fructosamine (FRA) have been utilized widely as a markers of diabetes. Recently, glycated albumin (GA) has been pointed out as a new indicator. For the determination of GA, spectrophotometry combined with an affinity column method has been mainly used, however the procedure is complicated. Recently a two-column HPLC method (ion-exchange column and affinity column) has been developed by Shima. We have evaluated a GA analyzer GAA-2000 based on Shima's method. After a series of fundamental and performance evaluation studies, the GAA-2000 was found to be appropriate for our study. Reference values obtained from this equipment were 10.56-16.87%. Correlation coefficients based on GA using diabetic and diabetic nephropathy patient specimens (n = 87) were: FRA (r = 0.944) greater than HbA1c (r = 0.842) greater than Glucose (r = 0.510) Superoxide dismutase (SOD) and lipid peroxidase (LPO) with are produced in relation to active oxygen did not show a good correlation. Although we tried classify the patients according to juvenile (20-39), middle (40-64) and senile (greater than 65) the method of Asada et al., we could not find any distinct tendencies.

Impact of common genetic determinants of Hemoglobin A1c on type 2 diabetes risk and diagnosis in ancestrally diverse populations : A transethnic genome-wide meta-analysis

NARCIS (Netherlands)

Wheeler, Eleanor; Leong, Aaron; Liu, Ching-Ti; Hivert, Marie-France; Strawbridge, Rona J; Podmore, Clara; Li, Man; Yao, Jie; Sim, Xueling; Hong, Jaeyoung; Chu, Audrey Y; Zhang, Weihua; Wang, Xu; Chen, Peng; Maruthur, Nisa M; Porneala, Bianca C; Sharp, Stephen J; Jia, Yucheng; Kabagambe, Edmond K; Chang, Li-Ching; Chen, Wei-Min; Elks, Cathy E; Evans, Daniel S; Fan, Qiao; Giulianini, Franco; Go, Min Jin; Hottenga, Jouke-Jan; Hu, Yao; Jackson, Anne U; Kanoni, Stavroula; Kim, Young Jin; Kleber, Marcus E; Ladenvall, Claes; Lecoeur, Cecile; Lim, Sing-Hui; Lu, Yingchang; Mahajan, Anubha; Marzi, Carola; Nalls, Mike A; Navarro, Pau; Nolte, Ilja M; Sanna, Serena; van der Most, Peter J; Van Vliet-Ostaptchouk, Jana V.; Alizadeh, Behrooz Z; Hartman, Catharina A; Swertz, Morris; Oldehinkel, Albertine J; Snieder, Harold; Wolffenbuttel, Bruce H R

2017-01-01

Background Glycated hemoglobin (HbA1c) is used to diagnose type 2 diabetes (T2D) and assess glycemic control in patients with diabetes. Previous genome-wide association studies (GWAS) have identified 18 HbA1c-associated genetic variants. These variants proved to be classifiable by their likely

Impact of common genetic determinants of Hemoglobin A1c on type 2 diabetes risk and diagnosis in ancestrally diverse populations : A transethnic genome-wide meta-analysis

NARCIS (Netherlands)

Wheeler, Eleanor; Leong, Aaron; Liu, Ching-Ti; Hivert, Marie-France; Strawbridge, Rona J; Podmore, Clara; Li, Man; Yao, Jie; Sim, Xueling; Hong, Jaeyoung; Chu, Audrey Y; Zhang, Weihua; Wang, Xu; Chen, Peng; Maruthur, Nisa M; Porneala, Bianca C; Sharp, Stephen J; Jia, Yucheng; Kabagambe, Edmond K; Chang, Li-Ching; Chen, Wei-Min; Elks, Cathy E; Evans, Daniel S; Fan, Qiao; Giulianini, Franco; Go, Min Jin; Hottenga, Jouke-Jan; Hu, Yao; Jackson, Anne U; Kanoni, Stavroula; Kim, Young Jin; Kleber, Marcus E; Ladenvall, Claes; Lecoeur, Cecile; Lim, Sing-Hui; Lu, Yingchang; Mahajan, Anubha; Marzi, Carola; Nalls, Mike A; Navarro, Pau; Nolte, Ilja M; Rose, Lynda M; Rybin, Denis V; Sanna, Serena; Shi, Yuan; Stram, Daniel O; Takeuchi, Fumihiko; Tan, Shu Pei; van der Most, Peter J; van Vliet-Ostaptchouk, Jana V; Wong, Andrew; Yengo, Loic; Zhao, Wanting; Goel, Anuj; Martinez Larrad, Maria Teresa; Radke, Dörte; Salo, Perttu; Tanaka, Toshiko; van Iperen, Erik P A; Abecasis, Goncalo; Afaq, Saima; Alizadeh, Behrooz Z; Bertoni, Alain G; Bonnefond, Amelie; Böttcher, Yvonne; Bottinger, Erwin P; Campbell, Harry; Carlson, Olga D; Chen, Chien-Hsiun; Cho, Yoon Shin; Garvey, W Timothy; Gieger, Christian; Goodarzi, Mark O; Grallert, Harald; Hamsten, Anders; Hartman, Catharina A; Herder, Christian; Hsiung, Chao Agnes; Huang, Jie; Igase, Michiya; Isono, Masato; Katsuya, Tomohiro; Khor, Chiea-Chuen; Kiess, Wieland; Kohara, Katsuhiko; Kovacs, Peter; Lee, Juyoung; Lee, Wen-Jane; Lehne, Benjamin; Li, Huaixing; Liu, Jianjun; Lobbens, Stephane; Luan, Jian'an; Lyssenko, Valeriya; Meitinger, Thomas; Miki, Tetsuro; Miljkovic, Iva; Moon, Sanghoon; Mulas, Antonella; Müller, Gabriele; Müller-Nurasyid, Martina; Nagaraja, Ramaiah; Nauck, Matthias; Pankow, James S; Polasek, Ozren; Prokopenko, Inga; Ramos, Paula S; Rasmussen-Torvik, Laura J; Rathmann, Wolfgang; Rich, Stephen S; Robertson, Neil R; Roden, Michael; Roussel, Ronan; Rudan, Igor; Scott, Robert A; Scott, William R; Sennblad, Bengt; Siscovick, David S; Strauch, Konstantin; Sun, Shan-Liang; Swertz, Morris a.; Tajuddin, Salman M; Taylor, Kent D; Teo, Yik-Ying; Tham, Yih Chung; Tönjes, Anke; Wareham, Nicholas J; Willemsen, Gonneke; Wilsgaard, Tom; Hingorani, Aroon D; Egan, Josephine; Ferrucci, Luigi; Hovingh, G. Kees; Jula, Antti; Kivimaki, Mika; Kumari, Meena; Njølstad, Inger; Palmer, Colin N A; Serrano Ríos, Manuel; Stumvoll, Michael; Watkins, Hugh; Aung, Tin; Blüher, Matthias; Boehnke, Michael; Boomsma, Dorret I; Bornstein, Stefan R; Chambers, John C; Chasman, Daniel I; Chen, Yii-Der Ida; Chen, Yduan-Tsong; Cheng, Ching-Yu; Cucca, Francesco; de Geus, Eco J C; Deloukas, Panos; Evans, Michele K; Fornage, Myriam; Friedlander, Yechiel; Froguel, Philippe; Groop, Leif; Gross, Myron D; Harris, Tamara B; Hayward, Caroline; Heng, Chew-Kiat; Ingelsson, Erik; Kato, Norihiro; Kim, Bong-Jo; Koh, Woon-Puay; Kooner, Jaspal S; Körner, Antje; Kuh, Diana; Kuusisto, Johanna; Laakso, Markku; Lin, Xu; Liu, YongMei; Loos, Ruth J F; Magnusson, Patrik K E; März, Winfried; McCarthy, Mark I; Oldehinkel, Albertine J; Ong, Ken K; Pedersen, Nancy L; Pereira, Mark A; Peters, Annette; Ridker, Paul M; Sabanayagam, Charumathi; Sale, Michele; Saleheen, Danish; Saltevo, Juha; Schwarz, Peter Eh; Sheu, Wayne H H; Snieder, Harold; Spector, Timothy D; Tabara, Yasuharu; Tuomilehto, Jaakko; van Dam, Rob M; Wilson, James G; Wilson, James F; Wolffenbuttel, Bruce H R; Wong, Tien Yin; Wu, Jer-Yuarn; Yuan, Jian-Min; Zonderman, Alan B; Soranzo, Nicole; Guo, Xiuqing; Roberts, David J; Florez, Jose C; Sladek, Robert; Dupuis, Josée; Morris, Andrew P; Tai, E Shyong; Selvin, Elizabeth; Rotter, Jerome I; Langenberg, Claudia; Barroso, Inês; Meigs, James B

BACKGROUND: Glycated hemoglobin (HbA1c) is used to diagnose type 2 diabetes (T2D) and assess glycemic control in patients with diabetes. Previous genome-wide association studies (GWAS) have identified 18 HbA1c-associated genetic variants. These variants proved to be classifiable by their likely

Impact of common genetic determinants of Hemoglobin A1c on type 2 diabetes risk and diagnosis in ancestrally diverse populations : A transethnic genome-wide meta-analysis

NARCIS (Netherlands)

Wheeler, Eleanor; Leong, Aaron; Liu, Ching Ti; Hivert, Marie France; Strawbridge, Rona J.; Podmore, Clara; Li, Man; Yao, Jie; Sim, Xueling; Hong, Jaeyoung; Chu, Audrey Y.; Zhang, Weihua; Wang, Xu; Chen, Peng; Maruthur, Nisa M.; Porneala, Bianca C.; Sharp, Stephen J.; Jia, Yucheng; Kabagambe, Edmond K.; Chang, Li Ching; Chen, Wei Min; Elks, Cathy E.; Evans, Daniel S.; Fan, Qiao; Giulianini, Franco; Go, Min Jin; Hottenga, Jouke Jan; Hu, Yao; Jackson, Anne U.; Kanoni, Stavroula; Kim, Young Jin; Kleber, Marcus E.; Ladenvall, Claes; Lecoeur, Cecile; Lim, Sing Hui; Lu, Yingchang; Mahajan, Anubha; Marzi, Carola; Nalls, Mike A.; Navarro, Pau; Nolte, Ilja M.; Rose, Lynda M.; Rybin, Denis V.; Sanna, Serena; Shi, Yuan; Stram, Daniel O.; Takeuchi, Fumihiko; Tan, Shu Pei; van der Most, Peter J.; Van Vliet-Ostaptchouk, Jana V.; Wong, Andrew; Yengo, Loic; Zhao, Wanting; Goel, Anuj; Martinez Larrad, Maria Teresa; Radke, Dörte; Salo, Perttu; Tanaka, Toshiko; van Iperen, Erik P.A.; Abecasis, Goncalo; Afaq, Saima; Alizadeh, Behrooz Z.; Bertoni, Alain G.; Bonnefond, Amelie; Böttcher, Yvonne; Bottinger, Erwin P.; Campbell, Harry; Carlson, Olga D.; Chen, Chien Hsiun; Cho, Yoon Shin; Garvey, W. Timothy; Gieger, Christian; Goodarzi, Mark O.; Grallert, Harald; Hamsten, Anders; Hartman, Catharina A.; Herder, Christian; Hsiung, Chao Agnes; Huang, Jie; Igase, Michiya; Isono, Masato; Katsuya, Tomohiro; Khor, Chiea Chuen; Kiess, Wieland; Kohara, Katsuhiko; Kovacs, Peter; Lee, Juyoung; Lee, Wen Jane; Lehne, Benjamin; Li, Huaixing; Liu, Jianjun; Lobbens, Stephane; Luan, Jian'an; Lyssenko, Valeriya; Meitinger, Thomas; Miki, Tetsuro; Miljkovic, Iva; Moon, Sanghoon; Mulas, Antonella; Müller, Gabriele; Müller-Nurasyid, Martina; Nagaraja, Ramaiah; Nauck, Matthias; Pankow, James S.; Polasek, Ozren; Prokopenko, Inga; Ramos, Paula S.; Rasmussen-Torvik, Laura; Rathmann, Wolfgang; Rich, Stephen S.; Robertson, Neil R.; Roden, Michael; Roussel, Ronan; Rudan, Igor; Scott, Robert A.; Scott, William R.; Sennblad, Bengt; Siscovick, David S.; Strauch, Konstantin; Sun, Liang; Swertz, Morris; Tajuddin, Salman M.; Taylor, Kent D.; Teo, Yik Ying; Tham, Yih Chung; Tönjes, Anke; Wareham, Nicholas J.; Willemsen, Gonneke; Wilsgaard, Tom; Hingorani, Aroon D.; Egan, Josephine; Ferrucci, Luigi; Hovingh, G. Kees; Jula, Antti; Kivimaki, Mika; Kumari, Meena; Njølstad, Inger; Palmer, Colin N.A.; Serrano Ríos, Manuel; Stumvoll, Michael; Watkins, Hugh; Aung, Tin; Blüher, Matthias; Boehnke, Michael; Boomsma, Dorret I.; Bornstein, Stefan R.; Chambers, John C.; Chasman, Daniel I.; Chen, Yii Der Ida; Chen, Yduan Tsong; Cheng, Ching Yu; Cucca, Francesco; de Geus, Eco J.C.; Deloukas, Panos; Evans, Michele K.; Fornage, Myriam; Friedlander, Yechiel; Froguel, Philippe; Groop, Leif; Gross, Myron D.; Harris, Tamara B.; Hayward, Caroline; Heng, Chew Kiat; Ingelsson, Erik; Kato, Norihiro; Kim, Bong Jo; Koh, Woon Puay; Kooner, Jaspal S.; Körner, Antje; Kuh, Diana; Kuusisto, Johanna; Laakso, Markku; Lin, Xu; Liu, Yongmei; Loos, Ruth J.F.; Magnusson, Patrik K.E.; März, Winfried; McCarthy, Mark I.; Oldehinkel, Albertine J.; Ong, Ken K.; Pedersen, Nancy L.; Pereira, Mark A.; Peters, Annette; Ridker, Paul M.; Sabanayagam, Charumathi; Sale, Michele; Saleheen, Danish; Saltevo, Juha; Schwarz, Peter E.H.; Sheu, Wayne H.H.; Snieder, Harold; Spector, Timothy D.; Tabara, Yasuharu; Tuomilehto, Jaakko; van Dam, Rob M.; Wilson, James G.; Wilson, James F.; Wolffenbuttel, Bruce H.R.; Wong, Tien Yin; Wu, Jer Yuarn; Yuan, Jian Min; Zonderman, Alan B.; Soranzo, Nicole; Guo, Xiuqing; Roberts, David J.; Florez, Jose C.; Sladek, Robert; Dupuis, Josée; Morris, Andrew P.; Tai, E. Shyong; Selvin, Elizabeth; Rotter, Jerome I.; Langenberg, Claudia; Barroso, Inês; Meigs, James B.

2017-01-01

Background: Glycated hemoglobin (HbA1c) is used to diagnose type 2 diabetes (T2D) and assess glycemic control in patients with diabetes. Previous genome-wide association studies (GWAS) have identified 18 HbA1c-associated genetic variants. These variants proved to be classifiable by their likely

Impact of common genetic determinants of Hemoglobin A1c on type 2 diabetes risk and diagnosis in ancestrally diverse populations: A transethnic genome-wide meta-analysis

NARCIS (Netherlands)

Wheeler, Eleanor; Leong, Aaron; Liu, Ching-Ti; Hivert, Marie-France; Strawbridge, Rona J.; Podmore, Clara; Li, Man; Yao, Jie; Sim, Xueling; Hong, Jaeyoung; Chu, Audrey Y.; Zhang, Weihua; Wang, Xu; Chen, Peng; Maruthur, Nisa M.; Porneala, Bianca C.; Sharp, Stephen J.; Jia, Yucheng; Kabagambe, Edmond K.; Chang, Li-Ching; Chen, Wei-Min; Elks, Cathy E.; Evans, Daniel S.; Fan, Qiao; Giulianini, Franco; Go, Min Jin; Hottenga, Jouke-Jan; Hu, Yao; Jackson, Anne U.; Kanoni, Stavroula; Kim, Young Jin; Kleber, Marcus E.; Ladenvall, Claes; Lecoeur, Cecile; Lim, Sing-Hui; Lu, Yingchang; Mahajan, Anubha; Marzi, Carola; Nalls, Mike A.; Navarro, Pau; Nolte, Ilja M.; Rose, Lynda M.; Rybin, Denis V.; Sanna, Serena; Shi, Yuan; Stram, Daniel O.; Takeuchi, Fumihiko; Tan, Shu Pei; van der Most, Peter J.; van Vliet-Ostaptchouk, Jana V.; Wong, Andrew; Yengo, Loic; Zhao, Wanting; Goel, Anuj; Martinez Larrad, Maria Teresa; Radke, Dorte; Salo, Perttu; Tanaka, Toshiko; van Iperen, Erik P. A.; Abecasis, Goncalo; Afaq, Saima; Alizadeh, Behrooz Z.; Bertoni, Alain G.; Bonnefond, Amelie; Bottcher, Yvonne; Bottinger, Erwin P.; Campbell, Harry; Carlson, Olga D.; Chen, Chien-Hsiun; Cho, Yoon Shin; Garvey, W. Timothy; Gieger, Christian; Goodarzi, Mark O.; Grallert, Harald; Hamsten, Anders; Hartman, Catharina A.; Herder, Christian; Hsiung, Chao Agnes; Huang, Jie; Igase, Michiya; Isono, Masato; Katsuya, Tomohiro; Khor, Chiea-Chuen; Kiess, Wieland; Kohara, Katsuhiko; Kovacs, Peter; Lee, Juyoung; Lee, Wen-Jane; Lehne, Benjamin; Li, Huaixing; Liu, Jianjun; Lobbens, Stephane; Luan, Jian'an; Lyssenko, Valeriya; Meitinger, Thomas; Miki, Tetsuro; Miljkovic, Iva; Moon, Sanghoon; Mulas, Antonella; Muller, Gabriele; Muller-Nurasyid, Martina; Nagaraja, Ramaiah; Nauck, Matthias; Pankow, James S.; Polasek, Ozren; Prokopenko, Inga; Ramos, Paula S.; Rasmussen-Torvik, Laura; Rathmann, Wolfgang; Rich, Stephen S.; Robertson, Neil R.; Roden, Michael; Roussel, Ronan; Rudan, Igor; Scott, Robert A.; Scott, William R.; Sennblad, Bengt; Siscovick, David S.; Strauch, Konstantin; Sun, Liang; Swertz, Morris; Tajuddin, Salman M.; Taylor, Kent D.; teo, Yik-Ying; Tham, Yih Chung; Tonjes, Anke; Wareham, Nicholas J.; Willemsen, Gonneke; Wilsgaard, Tom; Hingorani, Aroon D.; Egan, Josephine; Ferrucci, Luigi; Hovingh, G. Kees; Jula, Antti; Kivimaki, Mika; Kumari, Meena; Njolstad, Inger; Palmer, Colin N. A.; Serrano Rios, Manuel; Stumvoll, Michael; Watkins, Hugh; Aung, Tin; Bluher, Matthias; Boehnke, Michael; Boomsma, Dorret I.; Bornstein, Stefan R.; Chambers, John C.; Chasman, Daniel I.; Chen, Yii-Der Ida; Chen, Yduan-Tsong; Cheng, Ching-Yu; Cucca, Francesco; de Geus, Eco J. C.; Deloukas, Panos; Evans, Michele K.; Fornage, Myriam; Friedlander, Yechiel; Froguel, Philippe; Groop, Leif; Gross, Myron D.; Harris, Tamara B.; Hayward, Caroline; Heng, Chew-Kiat; Ingelsson, Erik; Kato, Norihiro; Kim, Bong-Jo; Koh, Woon-Puay; Kooner, Jaspal S.; Korner, Antje; Kuh, Diana; Kuusisto, Johanna; Laakso, Markku; Lin, Xu; Liu, Yongmei; Loos, Ruth J. F.; Magnusson, Patrik K. E.; Marz, Winfried; McCarthy, Mark I.; Oldehinkel, Albertine J.; Ong, Ken K.; Pedersen, Nancy L.; Pereira, Mark A.; Peters, Annette; Ridker, Paul M.; Sabanayagam, Charumathi; Sale, Michele; Saleheen, Danish; Saltevo, Juha; Schwarz, Peter Eh; Sheu, Wayne H. H.; Snieder, Harold; Spector, Timothy D.; Tabara, Yasuharu; Tuomilehto, Jaakko; van Dam, Rob M.; Wilson, James G.; Wilson, James F.; Wolffenbuttel, Bruce H. R.; Wong, Tien Yin; Wu, Jer-Yuarn; Yuan, Jian-Min; Zonderman, Alan B.; Soranzo, Nicole; Guo, Xiuqing; Roberts, David J.; Florez, Jose C.; Sladek, Robert; Dupuis, Josee; Morris, Andrew P.; Tai, E.-Shyong; Selvin, Elizabeth; Rotter, Jerome I.; Langenberg, Claudia; Barroso, Ines; Meigs, James B.

2017-01-01

Background Glycated hemoglobin (HbA1c) is used to diagnose type 2 diabetes (T2D) and assess glycemic control in patients with diabetes. Previous genome-wide association studies (GWAS) have identified 18 HbA1c-associated genetic variants. These variants proved to be classifiable by their likely

Inhibition of Protein Glycation by Tiger Milk Mushroom [Lignosus rhinocerus (Cooke Ryvarden] and Search for Potential Anti-diabetic Activity-Related Metabolic Pathways by Genomic and Transcriptomic Data Mining

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Hui-Yeng Y. Yap

2018-02-01

Full Text Available Naturally occurring anti-glycation compounds have drawn much interest in recent years as they show potential in reducing or preventing the risk of chronic complications for diabetic patients. In this study, annotation of the genome–transcriptome data from tiger milk mushroom (Lignosus rhinocerus, syn. Lignosus rhinocerotis to PlantCyc enzymes database identified transcripts that are related to anti-diabetic properties, and these include genes that are involved in carotenoid and abscisic acid biosynthesis as well as genes that code for glyoxalase I, catalase-peroxidases, and superoxide dismutases. The existence of these genes suggests that L. rhinocerus may contain bioactive compound(s with anti-glycation properties that can be exploited for management of diabetic complications. A medium-molecular-weight (MMW fraction which was obtained from a combination of cold water extraction and Sephadex® G-50 (fine gel filtration chromatography of L. rhinocerus sclerotia powder was demonstrated to exhibit potent anti-glycation activity. The fraction specifically inhibited the formation of N-(carboxymethyllysine, pentosidine, and other advanced glycation end-product (AGE structures in a human serum albumin-glucose system, with an IC50 value of 0.001 mg/ml, almost 520 times lower than that of the positive control, aminoguanidine hydrochloride (IC50 = 0.52 mg/ml. Its ability to suppress protein glycation may be partly associated with its strong superoxide anion radical scavenging activity (10.16 ± 0.12 mmol TE/g. Our results suggest that the MMW fraction of L. rhinocerus shows potential to be developed into a potent glycation inhibitor for preventing AGE-mediated diabetic complications.

A1C Combined With Glycated Albumin Improves Detection of Prediabetes in Africans: The Africans in America Study

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Duong, Michelle T.; Aldana, Paola C.; Ricks, Madia; Tulloch-Reid, Marshall K.; Lozier, Jay N.; Chung, Stephanie T.; Sacks, David B.

2016-01-01

OBJECTIVE Slowing the diabetes epidemic in Africa requires improved detection of prediabetes. A1C, a form of glycated hemoglobin A, is recommended for diagnosing prediabetes. The glycated proteins, fructosamine and glycated albumin (GA), are hemoglobin-independent alternatives to A1C, but their efficacy in Africans is unknown. Our goals were to determine the ability of A1C, fructosamine, and GA to detect prediabetes in U.S.-based Africans and the value of combining A1C with either fructosamine or GA. RESEARCH DESIGN AND METHODS Oral glucose tolerance tests (OGTT) were performed in 217 self-identified healthy African immigrants (69% male, age 39 ± 10 years [mean ± SD], BMI 27.6 ± 4.5 kg/m2). A1C, fructosamine, and GA were measured. Prediabetes was diagnosed by American Diabetes Association criteria for glucose obtained from a 2-h OGTT. The thresholds to diagnose prediabetes by A1C, fructosamine, and GA were the cutoff at the upper tertile for each variable: ≥5.7% (39 mmol/mol) (range 4.2–6.6% [22.4–48.6 mmol/mol]), ≥230 µmol/L (range 161–269 µmol/L), and ≥13.35% (range 10.20–16.07%), respectively. RESULTS Prediabetes occurred in 34% (74 of 217). The diagnostic sensitivities of A1C, fructosamine, and GA were 50%, 41%, and 42%, respectively. The P values for comparison with A1C were both >0.3. Combining A1C with either fructosamine or GA increased sensitivities. However, the sensitivity of A1C combined with fructosamine was not better than for A1C alone (72% vs. 50%, P = 0.172). In contrast, the sensitivity of A1C combined with GA was higher than for A1C alone (78% vs. 50%, P prediabetes. However, combining A1C with GA made it possible to identify nearly 80% of Africans with prediabetes. PMID:26681716

Revaluation of biological variation of glycated hemoglobin (HbA(1c)) using an accurately designed protocol and an assay traceable to the IFCC reference system.

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Braga, Federica; Dolci, Alberto; Montagnana, Martina; Pagani, Franca; Paleari, Renata; Guidi, Gian Cesare; Mosca, Andrea; Panteghini, Mauro

2011-07-15

Glycated hemoglobin (HbA(1c)) has a key role for diagnosing diabetes and monitoring glycemic state. As recently reviewed, available data on HbA(1c) biological variation show marked heterogeneity. Here we experimentally revaluated these data using a well designed protocol. We took five EDTA whole blood specimens from 18 apparently healthy subjects on the same day, every two weeks for two months. Samples were stored at -80°C until analysis and assayed in duplicate in a single run by Roche Tina-quant® Gen.2 immunoassay. Data were analyzed by the ANOVA. To assess the assay traceability to the IFCC reference method, we preliminarily carried out a correlation experiment. The bias (mean±SD) of the Roche immunoassay was 0.3%±0.7%, confirming the traceability of the employed assay. No difference was found in HbA(1c) values between men and women. Within- and between-subject CV were 2.5% and 7.1%, respectively. Derived desirable analytical goals for imprecision, bias, and total error resulted 1.3%, 1.9%, and 3.9%, respectively. HbA(1c) had marked individuality, limiting the use of population-based reference limits for test interpretation. The estimated critical difference was ~10%. For the first time we defined biological variation and derived indices for the clinical application of HbA(1c) measurements using an accurately designed protocol and an assay standardized according to the IFCC. Copyright © 2011 Elsevier B.V. All rights reserved.

Glycation Reactions of Casein Micelles.

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Moeckel, Ulrike; Duerasch, Anja; Weiz, Alexander; Ruck, Michael; Henle, Thomas

2016-04-13

After suspensions of micellar casein or nonmicellar sodium caseinate had been heated, respectively, in the presence and absence of glucose for 0-4 h at 100 °C, glycation compounds were quantitated. The formation of Amadori products as indicators for the "early" Maillard reaction were in the same range for both micellar and nonmicellar caseins, indicating that reactive amino acid side chains within the micelles are accessible for glucose in a comparable way as in nonmicellar casein. Significant differences, however, were observed concerning the formation of the advanced glycation end products (AGEs), namely, N(ε)-carboxymethyllysine (CML), pyrraline, pentosidine, and glyoxal-lysine dimer (GOLD). CML could be observerd in higher amounts in nonmicellar casein, whereas in the micelles the pyrraline formation was increased. Pentosidine and GOLD were formed in comparable amounts. Furthermore, the extent of protein cross-linking was significantly higher in the glycated casein micelles than in the nonmicellar casein samples. Dynamic light scattering and scanning electron microscopy showed that glycation has no influence on the size of the casein micelles, indicating that cross-linking occurs only in the interior of the micelles, but altered the surface morphology. Studies on glycation and nonenzymatic cross-linking can contribute to the understanding of the structure of casein micelles.

The association between nonadherence and glycated hemoglobin among type 2 diabetes patients using basal insulin analogs

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DiBonaventura M

2014-06-01

Full Text Available Marco DiBonaventura,1 Neil Wintfeld,2 Joanna Huang,2 Amir Goren1 1Health Outcomes Practice, Kantar Health, New York, NY, 2Health Economics and Outcomes Research, Novo Nordisk, Princeton, NJ, USA Background: The main objective of this study was to investigate the relationship between adherence and both clinical (ie, glycated hemoglobin [HbA1c] and nonclinical (ie, health status, work impairment, and health care-resource use health outcomes among type 2 diabetes (T2D patients using basal insulin. Materials and methods: The 2012 US National Health and Wellness Survey dataset was used for this study (n=71,141. A total of 1,198 respondents who reported a diagnosis of T2D, were currently using basal insulin, and reported both their HbA1c and level of nonadherence were included in the analyses. Classical test theory and item response theory (IRT analyses were used to provide evidence for the Morisky Medication Adherence Scale (MMAS in this population. Adherence was then used as a predictor of HbA1c and nonclinical outcomes using regression modeling, controlling for demographics and health history. Results: A total of 61.44% of respondents were male, and the mean age was 60.65 (standard deviation 10.74 years. Internal consistency of the eight-item MMAS (MMAS-8 was adequate (Cronbach's α=0.68, and one factor was retained (eigenvalue =1.80. IRT analyses suggested that the MMAS-8 was most precise for those with high levels of nonadherence. A significant relationship between variables emerged, whereby each point increase in the level of nonadherence was associated with a 0.21 increase in HbA1c (B=0.212, P<0.05. A modest quadratic trend was also observed (B=0.026, P<0.05, indicating that the benefit to HbA1c may taper off at high adherence. Each point of nonadherence was associated with a 4.6%, 20.4%, and 20.9% increase in the number of physician visits, emergency room visits, and hospitalizations, respectively. Discussion: This study provides evidence that

Inhibitory potential of pure isoflavonoids, red clover, and alfalfa extracts on hemoglobin glycosylation

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Mohsen Hosseini

2015-03-01

Full Text Available BACKGROUND: Non-enzymatic glycosylation of hemoglobin is complications of diabetes. Antioxidant system imbalance can result in the emergence of free radicals’ destructive effects in the long-term. Red clover (Trifolium pratense L. and alfalfa (Medicago sativa L. contain isoflavonoids and have antioxidant activity. This experimental study evaluated the inhibitory activity of pure isoflavonoids (daidzein and genistein, red clover and alfalfa extracts on hemoglobin glycosylation. METHODS: This study was performed in Iran. Stock solution of hydroalcoholic extracts of red clover and alfalfa in concentrations of 1 and 10 g/100 ml and stock solution of daidzein and genistein in concentrations of 250 ng, 500 ng, 25 µg and 250 µg/100 ml were prepared as case groups. Control group was without hydroalcoholic extracts of plants and pure isoflavonoids. All experiments were performed in triplicate. Hemoglobin was prepared and antioxidant activities were investigated to estimate degree of nonenzymatic hemoglobin glycosylation. RESULTS: There was no significantly difference between used extracts (extract of red clover and alfalfa and control of the hemoglobin glycosylation but using daidzein (P = 0.046, 0.029 and 0.021, respectively and genistein (P = 0.034, 0.036 and 0.028 significantly inhibited (P < 0.050 this reaction in 25 µg/100 ml, 250 and 500 ng/100 ml concentrations when compared to control. in 25 µg/100 ml, 250 ng and 500 ng/100 ml concentrations percentage of inhibition were 32, 80 and 74.5% respectively with used of daidzein and were 21, 83 and 76% respectively with consumption of genistein. CONCLUSION: According to decrease of glycation of hemoglobin with isoflavonoids, two used plant in this study containing isoflavonoid may be useful on diabetes.   

Glycated Hemoglobin, Fasting Insulin and the Metabolic Syndrome in Males. Cross-Sectional Analyses of the Aragon Workers' Health Study Baseline.

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Saravia, Gabriela; Civeira, Fernando; Hurtado-Roca, Yamilee; Andres, Eva; Leon, Montserrat; Pocovi, Miguel; Ordovas, Jose; Guallar, Eliseo; Fernandez-Ortiz, Antonio; Casasnovas, Jose Antonio; Laclaustra, Martin

2015-01-01

Glycated hemoglobin (HbA1c) is currently used to diagnose diabetes mellitus, while insulin has been relegated to research. Both, however, may help understanding the metabolic syndrome and profiling patients. We examined the association of HbA1c and fasting insulin with clustering of metabolic syndrome criteria and insulin resistance as two essential characteristics of the metabolic syndrome. We used baseline data from 3200 non-diabetic male participants in the Aragon Workers' Health Study. We conducted analysis to estimate age-adjusted odds ratios (ORs) across tertiles of HbA1c and insulin. Fasting glucose and Homeostatic model assessment - Insulin Resistance were used as reference. Here we report the uppermost-to-lowest tertile ORs (95%CI). Mean age (SD) was 48.5 (8.8) years and 23% of participants had metabolic syndrome. The ORs for metabolic syndrome criteria tended to be higher across HbA1c than across glucose, except for high blood pressure. Insulin was associated with the criteria more strongly than HbA1c and similarly to Homeostatic model assessment - Insulin Resistance (HOMA-IR). For metabolic syndrome, the OR of HbA1c was 2.68, of insulin, 11.36, of glucose, 7.03, and of HOMA-IR, 14.40. For the clustering of 2 or more non-glycemic criteria, the OR of HbA1c was 2.10, of insulin, 8.94, of glucose, 1.73, and of HOMA-IR, 7.83. All ORs were statistically significant. The areas under the receiver operating characteristics curves for metabolic syndrome were 0.670 (across HbA1c values) and 0.770 (across insulin values), and, for insulin resistance, 0.647 (HbA1c) and 0.995 (insulin). Among non-metabolic syndrome patients, a small insulin elevation identified risk factor clustering. HbA1c and specially insulin levels were associated with metabolic syndrome criteria, their clustering, and insulin resistance. Insulin could provide early information in subjects prone to develop metabolic syndrome.

Glycation inhibitors extend yeast chronological lifespan by reducing advanced glycation end products and by back regulation of proteins involved in mitochondrial respiration.

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Kazi, Rubina S; Banarjee, Reema M; Deshmukh, Arati B; Patil, Gouri V; Jagadeeshaprasad, Mashanipalya G; Kulkarni, Mahesh J

2017-03-06

Advanced Glycation End products (AGEs) are implicated in aging process. Thus, reducing AGEs by using glycation inhibitors may help in attenuating the aging process. In this study using Saccharomyces cerevisiae yeast system, we show that Aminoguanidine (AMG), a well-known glycation inhibitor, decreases the AGE modification of proteins in non-calorie restriction (NR) (2% glucose) and extends chronological lifespan (CLS) similar to that of calorie restriction (CR) condition (0.5% glucose). Proteomic analysis revealed that AMG back regulates the expression of differentially expressed proteins especially those involved in mitochondrial respiration in NR condition, suggesting that it switches metabolism from fermentation to respiration, mimicking CR. AMG induced back regulation of differentially expressed proteins could be possibly due to its chemical effect or indirectly by glycation inhibition. To delineate this, Metformin (MET), a structural analog of AMG and a mild glycation inhibitor and Hydralazine (HYD), another potent glycation inhibitor but not structural analog of AMG were used. HYD was more effective than MET in mimicking AMG suggesting that glycation inhibition was responsible for restoration of differentially expressed proteins. Thus glycation inhibitors particularly AMG, HYD and MET extend yeast CLS by reducing AGEs, modulating the expression of proteins involved in mitochondrial respiration and possibly by scavenging glucose. This study reports the role of glycation in aging process. In the non-caloric restriction condition, carbohydrates such as glucose promote protein glycation and reduce CLS. While, the inhibitors of glycation such as AMG, HYD, MET mimic the caloric restriction condition by back regulating deregulated proteins involved in mitochondrial respiration which could facilitate shift of metabolism from fermentation to respiration and extend yeast CLS. These findings suggest that glycation inhibitors can be potential molecules that can be used

Effectiveness of an Interprofessional Glycemic Optimization Clinic on Preoperative Glycated Hemoglobin Levels for Adult Patients with Type 2 Diabetes Undergoing Bariatric Surgery.

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Houlden, Robyn L; Yen, Joy L; Moore, Sarah

2017-12-26

Bariatric surgery is an effective treatment for patients with type 2 diabetes and refractory obesity; however, many patients have nonoptimal glycemic control preoperatively. We created an interprofessional bariatric glycemic optimization clinic. Patients were seen monthly and received weekly phone calls. We analyzed the effectiveness in assisting patients reach a preoperative glycated hemoglobin (A1C) level of weight was 134.4±29.2 kg. Baseline body mass index was 48.2±8.3 kg/m 2 . Duration of diabetes was 9±7.9 years. Baseline A1C level was 9.0±1.2%. Number of antihyperglycemic agents at baseline was 2.7±0.96. Seventy-five percent reached a target A1C level of ≤7.5%, 92% reached a target of ≤8.0% and 95% reached a target of ≤8.5%; 32% had achieved A1C levels ≤7.5% at 1 month, 59% at 2 months, 70% at 3 months, 73% at 4 months and 75% at 5 months. Mean number of antihyperglycemic agents at target A1C levels was 3.6±1.1. Mean absolute decrease in A1C levels from baseline to target A1C levels was 1.7±1.2. Mean absolute change in weight was -1.9±8.0 kg. Percent change in body weight from baseline to target A1C level was -1.3±4.9%. Glycemic optimization for candidates with diabetes for bariatric surgery is possible in a short time by an interprofessional diabetes team and without weight gain. Further research is needed to determine whether better preoperative glycemic control improves bariatric surgery outcomes. Copyright © 2018. Published by Elsevier Inc.

Can glycated hemoglobin act as a reliable glycemic indicator in patients with diabetic chronic kidney disease? evidence from the Northeast of Thailand

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Sojib Bin Zaman

2017-08-01

Full Text Available Background: Chronic kidney diseases (CKD is a common microvascular complication in patients with diabetes mellitus (DM which requires adequate glycemic control. Glycated hemoglobin (HbA1c is a conventional biomarker to estimate glycemic status, but its role in diabetic CKD patients is unclear. Therefore, this study aimed to determine whether patients with high HbA1c are associated to develop diabetic CKD.Methods: Data were obtained from a clinical registry of diabetic patients who were treated in a district hospital in the Northeast of Thailand. CKD was defined according to the estimated glomerular filtration rate (eGFR<60mL/min/1.73m2. Anthropometric and biochemical measurements of the patient were taken by review of medical records. Multiple logistic regression analysis was used to determine the likelihood of the association between HbA1c and CKD.Results: Among 4,050 participants, 1,027 (25.3% developed diabetic CKD. Older age (adjusted odds ratio (AOR: 4.88, 95% confidence interval (CI: 3.71–6.42, p<0.05, female (AOR: 1.38, 95% CI: 1.05–1.73, p<0.05, and hypertension (AOR: 1.52, 95% CI: 1.21–1.91, p<0.05 were found as the risk factors of diabetic CKD. However, patients with high HbA1c (>6.5% were negatively associated with diabetic CKD (AOR: 0.66, 95% CI: 0.51–0.86, p<0.05.Conclusion: This study found patients with higher HbA1c level were not associated with diabetic CKD. Therefore, using the conventional cut-off values of HbA1c in diabetic CKD patients may be problematic in the clinical settings. Enhanced detection of glycemic status in patients with diabetic CKD is warranted to improve the outcome.

Comparative LC-MS/MS profiling of free and protein-bound early and advanced glycation-induced lysine modifications in dairy products

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Hegele, Joerg; Buetler, Timo; Delatour, Thierry

2008-01-01

Free and protein-bound forms of early and advanced glycation-induced lysine (Lys) modifications were quantified in dairy products by LC-MS/MS using a stable isotope dilution assay. The glycation profiles for N ε -fructoselysine (FL), N ε -carboxymethyllysine (CML) and pyrraline (Pyr) were monitored in raw and processed cow milk to investigate whether free glycation products could serve as fast and simple markers to assess the extent of protein glycation in dairy products. In all milk samples, the fraction of free glycation adducts was predominantly composed of advanced modifications, e.g. 8.34 ± 3.81 nmol CML per μmol of free Lys (Lys free ) and 81.5 ± 87.8 nmol Pyr μmol -1 Lys free -1 vs. 3.72 ± 1.29 nmol FL μmol -1 Lys free -1 . In contrast, the protein-bound early glycation product FL considerably outweighed the content of CML and Pyr in milk proteins of raw and processed cow milk, whereas severely heat treated milk products, e.g. condensed milk, contained a higher amount of protein-bound advanced glycation adducts. Typical values recorded for milk samples processed under mild conditions were 0.47 ± 0.08 nmol FL μmol -1 of protein-bound Lys (Lys p-b ), 0.04 ± 0.03 nmol CML μmol -1 Lys p-b -1 and 0.06 ± 0.02 nmol Pyr μmol -1 Lys p-b -1 . It was particularly noticeable, however, that mild heat treatment of raw milk, i.e. pasteurization and UHT treatment, did not significantly increase the amount of both free and protein-bound Lys modifications. In conclusion, the profiles of free and protein-bound glycation-induced Lys modifications were found to be different and a screening of free glycation adducts does, therefore, not allow for a conclusion about the protein glycation status of dairy products

Glycated hemoglobin A1c level is associated with high urinary albumin/creatinine ratio in non-diabetic adult population.

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Kang, Seok Hui; Park, Jong Won; Do, Jun Young; Cho, Kyu Hyang

2016-09-01

Regarding the association between glycated hemoglobin A1c (HbA1c) levels and microvascular complications, high HbA1c level in participants without diabetes mellitus (DM) may be associated with a high urinary albumin-to-creatinine ratio (UACR). Twelve thousand seven hundred and seventy four participants without DM were included in this study. The participants were divided into three groups according to HbA1c levels: a Low group (High group (>6.0%). A high UACR was defined as UACR ≥3.9 mg/g for men and UACR ≥7.5 mg/g for women. The proportions of participants with a high UACR in the Low, Middle, and High groups were 22.4%, 27.9%, and 38.1%, respectively. Both univariate and multivariate analyses showed that logUACR was greatest in the High group compared to the other groups. For participants without metabolic syndrome (MetS), the proportions of participants with high UACR and logUACR values were greatest in the High group compared to the other groups. For participants with MetS, no differences were found for proportions of participants with high UACR and logUACR values in the Low, Middle, and High groups. Non-DM participants with relatively high HbA1c levels should be closely monitored for UACR, especially if participants do not have MetS. KEY MESSAGES HbA1c level was positively associated with the proportion of participants with a high UACR and logUACR in participants without DM. For participants without MetS, the proportion of participants with a high UACR was greater in the High group than in the other groups and logUACR was greatest in the High group compared to the other groups. For participants with MetS, there were significant associations between HbA1c and the proportion of participants with a high UACR as a categorical variable or logUACR as a continuous variable, but the statistical significance of this finding was weak. No differences were found for proportions of participants with high UACR and logUACR values in the Low, Middle, and High groups.

Protein Glycation in Diabetes as Determined by Mass Spectrometry

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Annunziata Lapolla

2013-01-01

Full Text Available Diabetes is a common endocrine disorder characterized by hyperglycemia leading to nonenzymatic glycation of proteins, responsible for chronic complications. The development of mass spectrometric techniques able to give highly specific and reliable results in proteome field is of wide interest for physicians, giving them new tools to monitor the disease progression and the possible complications related to diabetes, as well as the effectiveness of therapeutic treatments. This paper reports and discusses some of the data pertaining protein glycation in diabetic subjects obtained by matrix-assisted laser desorption ionization (MALDI mass spectrometry (MS. The preliminary studies carried out by in vitro protein glycation experiments show clear differences in molecular weight of glycated and unglycated proteins. Then, the attention was focused on plasma proteins human serum albumin (HSA and immunoglobulin G (IgG. Enzymatic degradation products of in vitro glycated HSA were studied in order to simulate the in vivo enzymatic digestion of glycated species by the immunological system leading to the highly reactive advanced glycation end-products (AGEs peptides. Further studies led to the evaluation of glycated Apo A-I and glycated haemoglobin levels. A different MALDI approach was employed for the identification of markers of disease in urine samples of healthy, diabetic, nephropathic, and diabetic-nephropathic subjects.

The effect of glycation on bovine serum albumin conformation and ligand binding properties with regard to gliclazide

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Żurawska-Płaksej, Ewa; Rorbach-Dolata, Anna; Wiglusz, Katarzyna; Piwowar, Agnieszka

2018-01-01

may have a direct impact on the free drug fraction and its pharmacokinetic behavior, including the risk of hypoglycemic episodes or unexpected interactions with other ligands. The use of BSA in examining binding effects upon glycation seems to be good model for preliminary research and may be used to identify a potential drug response in a diabetic state.

Optical noninvasive calculation of hemoglobin components concentrations and fractional oxygen saturation using a ring-scattering pulse oximeter

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Abdallah, Omar; Stork, Wilhelm; Muller-Glaser, Klaus

2004-06-01

The deficiencies of the currently used pulse oximeter are discussed in diverse literature. A hazardous pitfalls of this method is that the pulse oximeter will not detect carboxyhemoglobin (COHb) and methemoglobin (metHb) concentrations. This leads to incorrect measurement of oxygen saturation by carbon monoxide poisoning and methemoglobinemia. Also the total hemoglobin concentration will not be considered and can only be measured in-vitro up to now. A second pitfall of the standard pulse oximetry is that it will not be able to show a result by low perfusion of tissues. This case is available inter alia when the patient is under shock or has a low blood pressure. The new non-invasive system we designed measures the actual (fractional) oxygen saturation and hemoglobin concentration. It will enable us also to measure COHb and metHb. The measurement can be applied at better perfused body central parts. Four or more light emitting diodes (LEDs) or laser diodes (LDs) and five photodiodes (PDs) are used. The reflected light signal detected by photodiodes is processed using a modified Lambert-Beer law (I=I0×e-α.d ). According to this law, when a non scattering probe is irradiated with light having the incident intensity I0, the intensity of transmitted light I decays exponentially with the absorption coefficient a of that probe and its thickness d. Modifications of this law have been performed following the theoretical developed models in literature, Monte Carlo simulation and experimental measurement.

Association of reduced zinc status with poor glycemic control in individuals with type 2 diabetes mellitus.

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Bandeira, Verônica da Silva; Pires, Liliane Viana; Hashimoto, Leila Leiko; Alencar, Luciane Luca de; Almondes, Kaluce Gonçalves Sousa; Lottenberg, Simão Augusto; Cozzolino, Silvia Maria Franciscato

2017-12-01

This study evaluated the relationship between the zinc-related nutritional status and glycemic and insulinemic markers in individuals with type 2 diabetes mellitus (T2DM). A total of 82 individuals with T2DM aged between 29 and 59 years were evaluated. The concentration of zinc in the plasma, erythrocytes, and urine was determined by the flame atomic absorption spectrometry method. Dietary intake was assessed using a 3-day 24-h recall. In addition, concentrations of serum glucose, glycated hemoglobin percentage, total cholesterol and fractions, triglycerides, and serum insulin were determined. The insulin resistance index (HOMA-IR) and β-cell function (HOMA- β) were calculated. The markers of zinc status (plasma: 83.3±11.9μg/dL, erythrocytes: 30.1±4.6μg/g Hb, urine: 899.1±622.4μg Zn/24h, and dietary: 9.9±0.8mg/day) were classified in tertiles and compared to insulinemic and glycemic markers. The results showed that lower zinc concentrations in plasma and erythrocytes, as well as its high urinary excretion, were associated with higher percentages of glycated hemoglobin, reflecting a worse glycemic control in individuals with T2DM (pzinc levels and glycated hemoglobin percentage (r=-0.325, p=0.003), and a positive correlation between urinary zinc excretion and glycemia (r=0.269, p=0.016), glycated hemoglobin percentage (r=0.318, p=0.004) and HOMA-IR (r=0.289, p=0.009). According to our study results, conclude that T2DM individuals with reduced zinc status exhibited poor glycemic control. Copyright © 2017 Elsevier GmbH. All rights reserved.

A study on human serum albumin influence on glycation of fibrinogen

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Kielmas, Martyna; Szewczuk, Zbigniew; Stefanowicz, Piotr

2013-01-01

Highlights: •The glycation of fibrinogen was investigated by isotopic labeling method. •The potential glycation sites in fibrinogen were identified. •Human serum albumin (HSA) inhibits the glycation of fibrinogen. •The effect of HSA on fibrinogen glycation is sequence-dependent. -- Abstract: Although in vivo glycation proceeds in complex mixture of proteins, previous studies did not take in consideration the influence of protein–protein interaction on Maillard reaction. The aim of our study was to test the influence of human serum albumin (HSA) on glycation of fibrinogen. The isotopic labeling using [ 13 C 6 ] glucose combined with LC-MS were applied as tool for identification possible glycation sites in fibrinogen and for evaluation the effect of HSA on the glycation level of selected amino acids in fibrinogen. The obtained data indicate that the addition of HSA protects the fibrinogen from glycation. The level of glycation in presence of HSA is reduced by 30–60% and depends on the location of glycated residue in sequence of protein

A study on human serum albumin influence on glycation of fibrinogen

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Kielmas, Martyna; Szewczuk, Zbigniew; Stefanowicz, Piotr, E-mail: Piotr.stefanowicz@chem.uni.wroc.pl

2013-09-13

Highlights: •The glycation of fibrinogen was investigated by isotopic labeling method. •The potential glycation sites in fibrinogen were identified. •Human serum albumin (HSA) inhibits the glycation of fibrinogen. •The effect of HSA on fibrinogen glycation is sequence-dependent. -- Abstract: Although in vivo glycation proceeds in complex mixture of proteins, previous studies did not take in consideration the influence of protein–protein interaction on Maillard reaction. The aim of our study was to test the influence of human serum albumin (HSA) on glycation of fibrinogen. The isotopic labeling using [{sup 13}C{sub 6}] glucose combined with LC-MS were applied as tool for identification possible glycation sites in fibrinogen and for evaluation the effect of HSA on the glycation level of selected amino acids in fibrinogen. The obtained data indicate that the addition of HSA protects the fibrinogen from glycation. The level of glycation in presence of HSA is reduced by 30–60% and depends on the location of glycated residue in sequence of protein.

Glycated albumin: from biochemistry and laboratory medicine to clinical practice.

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Dozio, Elena; Di Gaetano, Nicola; Findeisen, Peter; Corsi Romanelli, Massimiliano Marco

2017-03-01

This review summarizes current knowledge about glycated albumin. We review the changes induced by glycation on the properties of albumin, the pathological implications of high glycated albumin levels, glycated albumin quantification methods, and the use of glycated albumin as a complementary biomarker for diabetes mellitus diagnosis and monitoring and for dealing with long-term complications. The advantages and limits of this biomarker in different clinical settings are also discussed.

Characterization and cytological effects of a novel glycated gelatine substrate

International Nuclear Information System (INIS)

Boonkaew, Benjawan; Supaphol, Pitt; Tompkins, Kevin; Manokawinchoke, Jeeranan; Pavasant, Prasit

2014-01-01

Hyperglycemia in diabetes results in the glycation of long-lived proteins. Protein glycation leads to the formation of advanced glycation end products (AGEs), which are implicated in delayed wound healing and other diabetes-associated pathologies, one of which is periodontal disease. Research into the mechanisms by which glycated long-lived proteins such as collagen exert their effects can allow for the understanding of diabetic pathologies and the development of appropriate treatments. However, the high cost of purified protein can be a limitation for many laboratories around the world. The objective of this study was to develop a low-cost in vitro model of glycated gelatine as an alternative to the glycated collagen model. We investigated the glycation of gelatine type A, a denatured form of collagen, which is low-cost and abundantly available. In this study, gelatine was incubated for 7 days with ribose or methylglyoxal (MG). Cross-linking, autofluorescence and UV–Vis spectrophotometry assays were performed and indicated a dose-dependent linear increase in cross-linking and autofluorescence of gelatine by ribose and MG. MG produced more cross-linking compared to ribose at the same concentrations. The UV–Vis spectra of the glycated gelatines confirmed the presence of AGE fluorophores. Because diabetes is a risk factor for periodontal disease, the effect of the glycated substrates on the basic behaviour of human periodontal ligament (HPDL) cells was evaluated. Glycation dose dependently reduced HPDL attachment and cell spreading, indicating that the novel glycated gelatine substrate affects cell behaviour. These results show that gelatine glycated with ribose or MG can be used as low-cost in vitro models to study the effects of protein glycation on cell behaviour in diabetes and ageing. (paper)

Development of a screen-printed carbon electrode based disposable enzyme sensor strip for the measurement of glycated albumin.

Science.gov (United States)

Hatada, Mika; Tsugawa, Wakako; Kamio, Eri; Loew, Noya; Klonoff, David C; Sode, Koji

2017-02-15

Glycated proteins, such as glycated hemoglobin (HbA1c) or glycated albumin (GA) in the blood, are essential indicators of glycemic control for diabetes mellitus. Since GA, compared to HbA1c, is more sensitive to short term changes in glycemic levels, GA is expected to be used as an alternative or together with HbA1c as a surrogate marker indicator for glycemic control. In this paper we report the development of a sensing system for measuring GA by combining an enzyme analysis method, which is already used in clinical practice, with electrochemical principles. We used fructosyl amino acid oxidase, hexaammineruthenium(III) chloride as the electron mediator, and an inexpensive and economically attractive screen-printed carbon electrode. We used chronoamperometry to measure protease-digested GA samples. The developed sensor strips were able to measure protease-digested samples containing GA in very small sample volumes (1.3μL) within about 1min. We also prepared enzyme sensor strips suitable for clinical use in which the enzyme and the mediator were deposited and dried on. This sensor system showed a clear correlation between the GA concentration and the resulting current. The strips were stable following 3 months of storage at 37°C. We conclude that this disposable enzyme sensor strip system for measuring GA is suitable for point-of-care test (POCT) applications. Copyright © 2016 Elsevier B.V. All rights reserved.

Glycation inhibits trichloroacetic acid (TCA)-induced whey protein precipitation

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Four different WPI saccharide conjugates were successfully prepared to test whether glycation could inhibit WPI precipitation induced by trichloroacetic acid (TCA). Conjugates molecular weights after glycation were analyzed with SDS-PAGE. No significant secondary structure change due to glycation wa...

A1C Combined With Glycated Albumin Improves Detection of Prediabetes in Africans: The Africans in America Study.

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Sumner, Anne E; Duong, Michelle T; Aldana, Paola C; Ricks, Madia; Tulloch-Reid, Marshall K; Lozier, Jay N; Chung, Stephanie T; Sacks, David B

2016-02-01

Slowing the diabetes epidemic in Africa requires improved detection of prediabetes. A1C, a form of glycated hemoglobin A, is recommended for diagnosing prediabetes. The glycated proteins, fructosamine and glycated albumin (GA), are hemoglobin-independent alternatives to A1C, but their efficacy in Africans is unknown. Our goals were to determine the ability of A1C, fructosamine, and GA to detect prediabetes in U.S.-based Africans and the value of combining A1C with either fructosamine or GA. Oral glucose tolerance tests (OGTT) were performed in 217 self-identified healthy African immigrants (69% male, age 39 ± 10 years [mean ± SD], BMI 27.6 ± 4.5 kg/m(2)). A1C, fructosamine, and GA were measured. Prediabetes was diagnosed by American Diabetes Association criteria for glucose obtained from a 2-h OGTT. The thresholds to diagnose prediabetes by A1C, fructosamine, and GA were the cutoff at the upper tertile for each variable: ≥5.7% (39 mmol/mol) (range 4.2-6.6% [22.4-48.6 mmol/mol]), ≥230 µmol/L (range 161-269 µmol/L), and ≥13.35% (range 10.20-16.07%), respectively. Prediabetes occurred in 34% (74 of 217). The diagnostic sensitivities of A1C, fructosamine, and GA were 50%, 41%, and 42%, respectively. The P values for comparison with A1C were both >0.3. Combining A1C with either fructosamine or GA increased sensitivities. However, the sensitivity of A1C combined with fructosamine was not better than for A1C alone (72% vs. 50%, P = 0.172). In contrast, the sensitivity of A1C combined with GA was higher than for A1C alone (78% vs. 50%, P prediabetes. However, combining A1C with GA made it possible to identify nearly 80% of Africans with prediabetes. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Comparative LC-MS/MS profiling of free and protein-bound early and advanced glycation-induced lysine modifications in dairy products

Energy Technology Data Exchange (ETDEWEB)

Hegele, Joerg [Nestle Research Centre, Nestec Ltd., Vers-chez-les-Blanc, CH-1000 Lausanne 26 (Switzerland)], E-mail: joerg.hegele@rdls.nestle.com; Buetler, Timo; Delatour, Thierry [Nestle Research Centre, Nestec Ltd., Vers-chez-les-Blanc, CH-1000 Lausanne 26 (Switzerland)

2008-06-09

Free and protein-bound forms of early and advanced glycation-induced lysine (Lys) modifications were quantified in dairy products by LC-MS/MS using a stable isotope dilution assay. The glycation profiles for N{sup {epsilon}}-fructoselysine (FL), N{sup {epsilon}}-carboxymethyllysine (CML) and pyrraline (Pyr) were monitored in raw and processed cow milk to investigate whether free glycation products could serve as fast and simple markers to assess the extent of protein glycation in dairy products. In all milk samples, the fraction of free glycation adducts was predominantly composed of advanced modifications, e.g. 8.34 {+-} 3.81 nmol CML per {mu}mol of free Lys (Lys{sub free}) and 81.5 {+-} 87.8 nmol Pyr {mu}mol{sup -1} Lys{sub free}{sup -1} vs. 3.72 {+-} 1.29 nmol FL {mu}mol{sup -1} Lys{sub free}{sup -1}. In contrast, the protein-bound early glycation product FL considerably outweighed the content of CML and Pyr in milk proteins of raw and processed cow milk, whereas severely heat treated milk products, e.g. condensed milk, contained a higher amount of protein-bound advanced glycation adducts. Typical values recorded for milk samples processed under mild conditions were 0.47 {+-} 0.08 nmol FL {mu}mol{sup -1} of protein-bound Lys (Lys{sub p-b}), 0.04 {+-} 0.03 nmol CML {mu}mol{sup -1} Lys{sub p-b}{sup -1} and 0.06 {+-} 0.02 nmol Pyr {mu}mol{sup -1} Lys{sub p-b}{sup -1}. It was particularly noticeable, however, that mild heat treatment of raw milk, i.e. pasteurization and UHT treatment, did not significantly increase the amount of both free and protein-bound Lys modifications. In conclusion, the profiles of free and protein-bound glycation-induced Lys modifications were found to be different and a screening of free glycation adducts does, therefore, not allow for a conclusion about the protein glycation status of dairy products.

Evaluation of glycated albumin (GA) and GA/HbA1c ratio for diagnosis of diabetes and glycemic control: A comprehensive review.

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Yazdanpanah, Sara; Rabiee, Mohammad; Tahriri, Mohammadreza; Abdolrahim, Mojgan; Rajab, Asadollah; Jazayeri, Hossein E; Tayebi, Lobat

2017-06-01

Diabetes Mellitus (DM) is a group of metabolic diseases characterized by chronic high blood glucose concentrations (hyperglycemia). When it is left untreated or improperly managed, it can lead to acute complications including diabetic ketoacidosis and non-ketotic hyperosmolar coma. In addition, possible long-term complications include impotence, nerve damage, stroke, chronic kidney failure, cardiovascular disease, foot ulcers, and retinopathy. Historically, universal methods to measure glycemic control for the diagnosis of diabetes included fasting plasma glucose level (FPG), 2-h plasma glucose (2HP), and random plasma glucose. However, these measurements did not provide information about glycemic control over a long period of time. To address this problem, there has been a switch in the past decade to diagnosing diabetes and its severity through measurement of blood glycated proteins such as Hemoglobin A1c (HbA1c) and glycated albumin (GA). Diagnosis and evaluation of diabetes using glycated proteins has many advantages including high accuracy of glycemic control over a period of time. Currently, common laboratory methods used to measure glycated proteins are high-performance liquid chromatography (HPLC), immunoassay, and electrophoresis. HbA1c is one of the most important diagnostic factors for diabetes. However, some reports indicate that HbA1c is not a suitable marker to determine glycemic control in all diabetic patients. GA, which is not influenced by changes in the lifespan of erythrocytes, is thought to be a good alternative indicator of glycemic control in diabetic patients. Here, we review the literature that has investigated the suitability of HbA1c, GA and GA:HbA1c as indicators of long-term glycemic control and demonstrate the importance of selecting the appropriate glycated protein based on the patient's health status in order to provide useful and modern point-of-care monitoring and treatment.

Glycated hemoglobin: A powerful tool not used enough in primary care.

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Salinas, Maria; López-Garrigós, Maite; Flores, Emilio; Leiva-Salinas, Carlos

2018-03-01

Glycated haemoglobin (HbA1c) is one of the most useful and relevant laboratory tests currently available. The aim of the actual research was to study the variability and appropriateness in the request of HbA1c in primary care, and differences between regions, to assess if there would be an opportunity to improve the request. A cross-sectional study was conducted enrolling clinical Spanish laboratories. The number of HbA1c requested in 2014 by all general practitioners was reported by each participant. Test-utilization rate was expressed as tests per 1000 inhabitants. The index of variability was calculated, as the top decile divided by the bottom decile. HbA1c per 1000 inhabitants was compared between the different regions. To investigate whether HbA1c was appropriately requested to manage patients with diabetes, the real request was compared to the theoretically ideal number, according to prevalence of known diabetes mellitus in Spain and guideline recommendations. A total of 110 laboratories participated in the study, corresponding to a catchment area of 27 798 262 inhabitants (59.8% of the Spanish population) from 15 different autonomous communities (AACCs). 2 655 547 HbA1c were requested, a median of 93.9 (interquartile range (IQR): 33.4) per 1000 inhabitants. The variability index was 1.97. The HbA1c/1000 inhabitants was significantly different among the AACCs, ranging from 73.4 to 126.3. A total of 4 336 529 additional HbA1c would have been necessary to manage patients with diabetes according to guidelines, and 3 861 769 for diagnosis in asymptomatic patients. There was a high variability and significant differences between Spanish AACCs. Also a significant under-request of HbA1c was observed in Primary Care in Spain. © 2017 Wiley Periodicals, Inc.

Inhibition of protein glycation and advanced glycation end products ...

African Journals Online (AJOL)

Advanced glycation end products (AGEs) formation is increased in diabetes mellitus, leading to microvascular and macrovascular complications. Recently, much attention has been focused on natural and synthetic inhibitors to delay the onset or progression of diabetes and its comorbidities. Ascorbic acid (AA) can react with ...

Comparison of Hemoglobin A1c assay performance on two different commercial systems

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Jozo Ćorić

2015-04-01

Full Text Available Introduction: Glycated hemoglobin (HbA1c is formed by non-enzymatic binding of glucose to the free amino group of the N-terminal end of the ß-chain of hemoglobin A. HbA1c is representative of the mean blood glucose level over three months. The aim of the study was to evaluate the Hemoglobin A1c immunoturbidimetric assay performance on two different commercial systems.Methods: We evaluated the precision and trueness for determination of HbA1c in whole blood. Concentrations of total hemoglobin and HbA1c were evaluated on Dimension Xpand (Siemens and Cobas 501 (Roche analyzers. HbA1c was measured in a latex agglutination inhibition test. Commercial controls Liquichek Diabetes Control Level 1 and Liquichek Diabetes Control Level 2 (Bio Rad at two levels were used for quality control. Analytical validation of HbA1c included: within-run imprecision, between-day imprecision, inaccuracy and comparison determination on the human samples on 2 systems: Dimension Xpand and Cobas 501 analyzers. Results: Within-run imprecision on the commercially controls for Level 1 is 4.5% and Level 2 is 3.2% between-day imprecision on commercially controls is 6.1% Level 1 and 5.1% Level 2 for respectively inac- curacy on commercially controls for Level 1 is 1.8% and Level 2 is 4.8%. Method comparison on human samples shows the correlation coefficient of 0.99.Conclusion: The presented results of the analytical evaluation methods for the determination of HbA1c showed an acceptable accuracy and precision.

Difference between observed and predicted glycated hemoglobin at baseline and treatment response to vildagliptin-based dual oral therapy in patients with type 2 diabetes.

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Wang, Jun-Sing; Hung, Yi-Jen; Lu, Yung-Chuan; Tsai, Cheng-Lin; Yang, Wei-Shiung; Lee, Ting-I; Hsiao, Ya-Chun; Sheu, Wayne Huey-Herng

2018-04-01

We aimed to investigate the association of difference between observed and predicted glycated hemoglobin (dopHbA1c) and HbA1c reduction after vildagliptin-based oral therapy in patients with type 2 diabetes (T2D). This was a prospective observational study. Adults ≥ 20 years old with T2D and HbA1c ≧7% treated with oral anti-diabetic drugs (OADs) were eligible if their OADs were shifted to vildagliptin-based dual oral therapy. Fasting plasma glucose (FPG) and HbA1c were recorded at baseline, week 12, and week 24. To determine baseline dopHbA1c, a predicted HbA1c was calculated by inserting baseline FPG into a regression equation (HbA1c = FPG ∗ 0.0225 + 4.3806) developed from linear relationship between HbA1c and FPG in an independent cohort of 3239 outpatients with T2D (dopHbA1c = observed HbA1c - predicted HbA1c). Patients were assigned to low (≦0) or high (>0) dopHbA1c group according to their baseline dopHbA1c levels. The study endpoint was changes from baseline to week 24 in HbA1c levels. A total of 1224 patients were enrolled. Patients with a dopHbA1c >0 had a greater HbA1c reduction after vildagliptin-based dual oral therapy than those with a dopHbA1c ≦0 (-1.5 ± 2.0 vs. -0.4 ± 1.0%, p vildagliptin-based dual oral therapy. Copyright © 2018 Elsevier B.V. All rights reserved.

Profile of glycated-hemoglobin, antioxidant vitamin and cytokine levels in pulmonary tuberculosis patients: A cross sectional study at Pulmonary Diseases Center Semarang City, Indonesia

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Praba Ginandjar

2016-10-01

Full Text Available Background: Uncontrolled blood glucose, which marked by high level of HbA1c, increases risk of pulmonary TB because of cellular immunity dysfunction. This study aimed to analyze profile of glycated hemoglobin, antioxidant vitamins status and cytokines levels in active pulmonary TB patients. Methods: This was a cross sectional study, conducted at Pulmonary Diseases Center Semarang City, Indonesia. Study subject consisted of 62 pulmonary TB patients, diagnosed with positive acid fast bacilli and chest X-ray. ELISA was used to measure IFN-γ and IL-12. Status of antioxidant vitamins was determined by concentration of vitamin A and E using HPLC. Blood glucose control was determined by HbA1c concentration (HbA1c ≥7% is considered as uncontrolled. Results: A significant difference of age between pulmonary tuberculosis patients with normal and uncontrolled blood glucose (p = 0.000 was showed, while all other characteristics (sex, education, occupation did not differ with p = 0.050, 0.280, 0.380 respectively. Mean HbA1c was 7.25 ± 2.70%. Prevalence of uncontrolled glucose among pulmonary TB patients was 29%. Levels of IFN-γ and IL-12 did not differ according to HbA1c concentration (p = 0.159 and p = 0.965 respectively. Pulmonary tuberculosis patients with uncontrolled blood glucose has higher vitamin E (p = 0.006, while vitamin A did not differ significantly (p = 0.478. Conclusions: This study supports the importance of performing diabetes screening among pulmonary TB patients. Further study needs to be done to determine the feasibility of TB-DM co-management. Keywords: HbA1c, Pulmonary tuberculosis, Vitamin A, Vitamin E

The cutoffs and performance of glycated hemoglobin for diagnosing diabetes and prediabetes in a young and middle-aged population and in an elderly population.

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Yan, Shuang-Tong; Xiao, Hai-Ying; Tian, Hui; Li, Chun-Lin; Fang, Fu-Sheng; Li, Xiao-Ying; Cheng, Xiao-Ling; Li, Nan; Miao, Xin-Yu; Yang, Yan; Wang, Liang-Chen; Zou, Xiao-Man; Ma, Fang-Ling; He, Yao; Sai, Xiao-Yong

2015-08-01

The aims were to compare the appropriate cutoffs of glycated hemoglobin (HbA1c) in a population of varying ages and to evaluate the performance of HbA1c for diagnosing diabetes and prediabetes. A total of 1064 participants in the young and middle-aged group and 1671 in the elderly group were included and underwent HbA1c testing and an oral glucose tolerance test (OGTT). Sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) were calculated to evaluate the optimal HbA1c cutoffs. Kappa coefficients were used to test for agreement between HbA1c categorization and OGTT-based diagnoses. The optimal HbA1c cutoffs for diagnosing diabetes were 5.7% (39 mmol/mol) in the young and middle-aged group with a sensitivity of 66.7%, specificity of 86.7%, and AUC of 0.821 (95% CI: 0.686, 0.955) and 5.9% (41 mmol/mol) in the elderly group with a sensitivity of 80.4%, specificity of 73.3%, and AUC of 0.831 (0.801, 0.861). The optimal cutoffs for diagnosing prediabetes were 5.6% (38 mmol/mol) and 5.7% (39 mmol/mol) in the young and middle-aged group and in the elderly group, respectively. Agreement between the OGTT-based diagnosis of diabetes or prediabetes and the optimal HbA1c cutoff was low (all kappa coefficients prediabetes were appropriate. Furthermore, the performance of HbA1c for diagnosing diabetes and prediabetes was poor. HbA1c should be used in combination with traditional glucose criteria when detecting and diagnosing diabetes or prediabetes. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Longitudinal associations of nutritional factors with glycated hemoglobin in youth with type 1 diabetes: the SEARCH Nutrition Ancillary Study.

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Lamichhane, Archana P; Crandell, Jamie L; Jaacks, Lindsay M; Couch, Sarah C; Lawrence, Jean M; Mayer-Davis, Elizabeth J

2015-06-01

Improved glycated hemoglobin (Hb A1c) delays the progression of microvascular and macrovascular complications in individuals with type 1 diabetes (T1D). We previously showed that higher baseline intakes of n-3 (ω-3) fatty acids and leucine are associated with preserved β cell function 2 y later in youth with T1D. In the current study, we extend this work to explore the longitudinal associations of nutritional factors with Hb A1c in youth with T1D. We included 908 T1D youth with baseline and follow-up Hb A1c measurements. Nutritional factors assessed at baseline were as follows: breastfeeding status and timing of complimentary food introduction; intakes of leucine, carbohydrates, protein, fat, and fiber estimated from a food-frequency questionnaire (FFQ); and plasma biomarkers for vitamins D and E, eicosapentaenoic acid (EPA), and docosahexaenoic acid. We fit linear regression models adjusted for baseline Hb A1c, sociodemographic variables, diabetes-related variables, time between baseline and follow-up visits, saturated fat, physical activity, and for FFQ-derived nutrients, total calories. The vitamin D model was further adjusted for season and body mass index z score. The mean ± SD age and diabetes duration at baseline was 10.8 ± 3.9 y and 10.1 ± 5.8 mo, respectively. A total of 9.3% of participants had poor Hb A1c (value ≥9.5%) at baseline, which increased to 18.3% during follow-up (P 1). Intakes of EPA (β = -0.045, P = 0.046), leucine (β = -0.031, P = 0.0004), and protein (β = -0.003, P = 0.0002) were significantly negatively associated with follow-up Hb A1c after adjustment for confounders. Intake of carbohydrates was significantly positively (β = 0.001, P = 0.003) associated with follow-up Hb A1c after adjustment for confounders. Several nutritional factors may be associated with Hb A1c during early stages of disease progression in youth recently diagnosed with T1D. In addition to the overall role of major macronutrients such as carbohydrates and

Inhibition of Nonenzymatic Protein Glycation by Pomegranate and Other Fruit Juices

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Dorsey, Pamela Garner; Greenspan, Phillip

2014-01-01

Abstract The nonenzymatic glycation of proteins and the formation of advanced glycation endproducts in diabetes leads to the crosslinking of proteins and disease complications. Our study sought to demonstrate the effect of commonly consumed juices (pomegranate, cranberry, black cherry, pineapple, apple, and Concord grape) on the fructose-mediated glycation of albumin. Albumin glycation decreased by 98% in the presence of 10 μL of pomegranate juice/mL; other juices inhibited glycation by only 20%. Pomegranate juice produced the greatest inhibition on protein glycation when incubated at both the same phenolic concentration and the same antioxidant potential. Both punicalagin and ellagic acid significantly inhibited the glycation of albumin by ∼90% at 5 μg/mL. Sodium dodecyl sulfate–polyacrylamide gel electrophoresis revealed that pomegranate, but not apple juice, protected albumin from modification. These results demonstrate that pomegranate juice and two of its major constituents are potent inhibitors of fructose-mediated protein glycation. PMID:24433074

Ascorbic acid glycation of lens proteins produces UVA sensitizers similar to those in human lens

International Nuclear Information System (INIS)

Ortwerth, B.J.; Linetsky, Mikhail; Olesen, P.R.

1995-01-01

Soluble calf lens proteins were extensively glycated during a 4 week incubation with ascorbic acid in the presence of oxygen. Amino acids analysis of the dialyzed proteins removed at weekly intervals showed an increasing loss of lysine, arginine and histidine, consistent with the extensive protein cross-linking observed. Irradiation of the dialyzed samples with UVA light (1.0 kJ/cm 2 total illumination through a 338 nm cutoff filter) caused an increasing loss of tryptophan, an additional loss of histidine and the production of micromolar concentrations of hydrogen peroxide. No alteration in amino acid content and no photolytic effects were seen in proteins incubated without ascorbic acid in proteins incubated with glucose for 4 weeks. The rate of hydrogen peroxide formation was linear with each glycated sample with a maximum production of 25 nmol/mg protein illuminated. The possibility that the sensitizer activity was due to an ascorbate-induced oxidation of tryptophan was eliminated by the presence of a heavy metal ion chelator during the incubation and by showing equivalent effects with ascorbate-incubated ribonuclease A, which is devoid of tryptophan. The ascorbate-incubated samples displayed increasing absorbance at wavelengths above 300 nm and increasing fluorescence (340/430) as glycation proceeded. The spectra of the 4 week glycated proteins were identical to those obtained with a solubilized water-insoluble fraction from human lens, which is known to have UVA sensitizer activity. (Author)

Hemoglobin system of Sparus aurata: Changes in fishes farmed under extreme conditions

International Nuclear Information System (INIS)

Campo, Salvatore; Nastasi, Giancarlo; D'Ascola, Angela; Campo, Giuseppe M.; Avenoso, Angela; Traina, Paola; Calatroni, Alberto; Burrascano, Emanuele; Ferlazzo, Alida; Lupidi, Giulio; Gabbianelli, Rosita; Falcioni, Giancarlo

2008-01-01

In order to gain more knowledge on the stress responses of gilhead seabream (Sparus aurata) under extreme conditions, this study investigated the functional properties of the hemoglobin system and globin gene expression under hypoxia and low salinity. The oxygen affinity for the two hemoglobin components present inside the S. aurata erythrocyte was practically identical as was the influence of protons and organic phosphates (Root effect). The quantification of S. aurata hemoglobin fractions performed by HPLC and the data on gene expression of globin chains assayed by PCR indicate that under hypoxia and low salinity there is a change in the ratio between the two different hemoglobin components. The result indicating that the distinct hemoglobins present in S. aurata erythrocyte have almost identical functional properties, does not explain the adaptive response (expression change) following exposure of the animal to hypoxia or low salinity on the basis of their function as oxygen transporter. We hypothesize that other parallel biological functions that the hemoglobin molecule is known to display within the erythrocyte are involved in adaptive molecular mechanisms. The autoxidation-reduction cycle of hemoglobin could be involved in the response to particular living conditions

An enzymatic method for the rapid measurement of the hemoglobin A1c by a flow-injection system comprised of an electrochemical detector with a specific enzyme-reactor and a spectrophotometer

International Nuclear Information System (INIS)

Nanjo, Yoko; Hayashi, Ryuzo; Yao, Toshio

2007-01-01

A flow-injection analytical (FIA) system, comprised of an electrochemical detector with a fructosyl-peptide oxidase (FPOX-CET) reactor and a flow-type spectrophotometer, was proposed for the simultaneous measurement of glycohemoglobin and total hemoglobin in blood cell. The blood cell samples were hemolyzed with a surfactant and then treated with protease. In the first stage of operation, total hemoglobin in digested sample was determined spectrophotometrically. In the second stage, fructosyl valyl histidine (FVH) released from glycohemoglobin by the selective proteolysis was determined specifically using the electrochemical detector with the FPOX-CET reactor. The FIA system could be automatically processed at an analytical speed of 40 samples per hour. The proposed assay method could determine selectively only the glycated N-terminal residue of β-chain in glycohemoglobin and total hemoglobin in blood cell. The enzymatic hemoglobin A 1c (HbA 1c ) value calculated by the concentration ratio of the FVH to total hemoglobin, was closely correlated with the HbA 1c values certified by the Japan Diabetic Society (JDS) and the International Federation of Clinical Chemistry (IFCC)

Protective Effects of Ferulic Acid on High Glucose-Induced Protein Glycation, Lipid Peroxidation, and Membrane Ion Pump Activity in Human Erythrocytes.

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Weerachat Sompong

Full Text Available Ferulic acid (FA is the ubiquitous phytochemical phenolic derivative of cinnamic acid. Experimental studies in diabetic models demonstrate that FA possesses multiple mechanisms of action associated with anti-hyperglycemic activity. The mechanism by which FA prevents diabetes-associated vascular damages remains unknown. The aim of study was to investigate the protective effects of FA on protein glycation, lipid peroxidation, membrane ion pump activity, and phosphatidylserine exposure in high glucose-exposed human erythrocytes. Our results demonstrated that FA (10-100 μM significantly reduced the levels of glycated hemoglobin (HbA1c whereas 0.1-100 μM concentrations inhibited lipid peroxidation in erythrocytes exposed to 45 mM glucose. This was associated with increased glucose consumption. High glucose treatment also caused a significant reduction in Na+/K+-ATPase activity in the erythrocyte plasma membrane which could be reversed by FA. Furthermore, we found that FA (0.1-100 μM prevented high glucose-induced phosphatidylserine exposure. These findings provide insights into a novel mechanism of FA for the prevention of vascular dysfunction associated with diabetes.

Effect of glycation on α-crystallin structure and chaperone-like function

Science.gov (United States)

Kumar, P. Anil; Kumar, M. Satish; Reddy, G. Bhanuprakash

2007-01-01

The chaperone-like activity of α-crystallin is considered to play an important role in the maintenance of the transparency of the eye lens. However, in the case of aging and in diabetes, the chaperone function of α-crystallin is compromized, resulting in cataract formation. Several post-translational modifications, including non-enzymatic glycation, have been shown to affect the chaperone function of α-crystallin in aging and in diabetes. A variety of agents have been identified as the predominant sources for the formation of AGEs (advanced glycation end-products) in various tissues, including the lens. Nevertheless, glycation of α-crystallin with various sugars has resulted in divergent results. In the present in vitro study, we have investigated the effect of glucose, fructose, G6P (glucose 6-phosphate) and MGO (methylglyoxal), which represent the major classes of glycating agents, on the structure and chaperone function of α-crystallin. Modification of α-crystallin with all four agents resulted in the formation of glycated protein, increased AGE fluorescence, protein cross-linking and HMM (high-molecular-mass) aggregation. Interestingly, these glycation-related profiles were found to vary with different glycating agents. For instance, CML [Nϵ-(carboxymethyl)lysine] was the predominant AGE formed upon glycation of α-crystallin with these agents. Although fructose and MGO caused significant conformational changes, there were no significant structural perturbations with glucose and G6P. With the exception of MGO modification, glycation with other sugars resulted in decreased chaperone activity in aggregation assays. However, modification with all four sugars led to the loss of chaperone activity as assessed using an enzyme inactivation assay. Glycation-induced loss of α-crystallin chaperone activity was associated with decreased hydrophobicity. Furthermore, α-crystallin isolated from glycated TSP (total lens soluble protein) had also increased AGE

Hemoglobin C disease

Science.gov (United States)

Clinical hemoglobin C ... Hemoglobin C is an abnormal type of hemoglobin, the protein in red blood cells that carries oxygen. It is ... Americans. You are more likely to have hemoglobin C disease if someone in your family has had ...

Effects of non-enzymatic glycation in human serum albumin. Spectroscopic analysis

Science.gov (United States)

Szkudlarek, A.; Sułkowska, A.; Maciążek-Jurczyk, M.; Chudzik, M.; Równicka-Zubik, J.

2016-01-01

Human serum albumin (HSA), transporting protein, is exposed during its life to numerous factors that cause its functions become impaired. One of the basic factors - glycation of HSA - occurs in diabetes and may affect HSA-drug binding. Accumulation of advanced glycation end-products (AGEs) leads to diseases e.g. diabetic and non-diabetic cardiovascular diseases, Alzheimer disease, renal disfunction and in normal aging. The aim of the present work was to estimate how non-enzymatic glycation of human serum albumin altered its tertiary structure using fluorescence technique. We compared glycated human serum albumin by glucose (gHSAGLC) with HSA glycated by fructose (gHSAFRC). We focused on presenting the differences between gHSAFRC and nonglycated (HSA) albumin used acrylamide (Ac), potassium iodide (KI) and 2-(p-toluidino)naphthalene-6-sulfonic acid (TNS). Changes of the microenvironment around the tryptophan residue (Trp-214) of non-glycated and glycated proteins was investigated by the red-edge excitation shift method. Effect of glycation on ligand binding was examined by the binding of phenylbutazone (PHB) and ketoprofen (KP), which a primary high affinity binding site in serum albumin is subdomain IIA and IIIA, respectively. At an excitation and an emission wavelength of λex 335 nm and λem 420 nm, respectively the increase of fluorescence intensity and the blue-shift of maximum fluorescence was observed. It indicates that the glycation products decreases the polarity microenvironment around the fluorophores. Analysis of red-edge excitation shift method showed that the red-shift for gHSAFRC is higher than for HSA. Non-enzymatic glycation also caused, that the Trp residue of gHSAFRC becomes less accessible for the negatively charged quencher (I-), KSV value is smaller for gHSAFRC than for HSA. TNS fluorescent measurement demonstrated the decrease of hydrophobicity in the glycated albumin. KSV constants for gHSA-PHB systems are higher than for the unmodified serum

Pretreatment hemoglobin in early stage glottic cancer: red flag or red herring?

International Nuclear Information System (INIS)

Tucker, J. Curtis; Hixson, William C.; Kim, Robert Y.; Smith, Judy W.; Mayo, Matthew S.

1996-01-01

Purpose: To evaluate the impact of pretreatment hemoglobin levels on the recurrence rate of patients with early stage glottic carcinoma treated with definitive radiotherapy. Materials and Methods: Between May 1972 and December 1992, one hundred three patients with stage I or II glottic carcinoma were treated with definitive radiotherapy. The records were reviewed and analyzed for the effects of pretreatment hemoglobin and hematocrit, stage, dose per fraction (180 vs 200 cGy), treatment interruptions, and differentiation of the tumor. The majority of stage I patients were treated to a total dose of 64 to 66 Gy, and stage II patients were treated to 68 to 70 Gy. Mean and median follow up were 85 and 75 months, respectively. Results: With mean follow up of 85 months, the recurrence rate for patients with hemoglobin ≤13 g/dL was 33.3%, and patients with hemoglobin >13 g/dL was 20% (p 0.19). For stage I (n = 84), the recurrence rate with hemoglobin ≤13 g/dL and >13 g/dL was 26% and 17%, respectively (p = 0.51). For stage II patients (n = 19) with hemoglobin ≤13 g/dL and >13 g/dL, the recurrence rate was 50% and 36%, respectively (p = 0.66). Using a Fisher's exact test, the only variables showing a statistically significant prognosis for recurrence were treatment interruption and stage. The recurrence rate with a treatment interruption was 40% compared with 15% if there was no interruption (p 0.0039). The recurrence rate for stage I was 19%, and for stage II was 42% (p = 0.067). Other factors showed no significant increase in recurrence; dose per fraction (p = 0.421), grade of differentiation (p = 0.740). Conclusion: While pretreatment hemoglobin levels below 13 g/dL do not significantly affect the recurrence rates for T1N0 and T2N0 glottic carcinomas, treatment interruptions are a significant factor in the failure of these patients

Associations between basic indicators of inflammation and metabolic disturbances

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Sylwia Płaczkowska

2014-11-01

Full Text Available Background: Inflammation is involved in initiation and progression of diabetic complications related to cell damage of tissues, especially endothelial cells, and deepening of metabolic disturbances. This study was conducted in order to assess potential associations between basic laboratory parameters of inflammation and common metabolic factors such as glycated hemoglobin and C-reactive protein. Materials and methods: The studied group consisted of 95 patients with diabetes mellitus type 2 and 77 subjects without signs of disturbances in glucose metabolism, aged between 40 and 74 years. Fasting plasma glucose, glycated hemoglobin, complete blood count and high-sensitivity C-reactive protein concentration in blood were determined. Also blood pressure as well as weight and height measurements were taken to calculate BMI. Results: Fasting plasma glucose and glycated hemoglobin concentrations, total leukocyte count and granulocytes were significantly higher in diabetics. Significant correlations between both glycated hemoglobin and BMI and C-reactive protein concentration were noted. However, after adjusting for age and gender, leucocyte count was independently related to BMI and glycated hemoglobin, while C-reactive protein concentration was dependent on gender and BMI. Conclusion: Glycated hemoglobin as a marker of long-term glycemic control and BMI as an indicator of adipose tissue accumulation are significantly related to white blood cell count and C-reactive protein concentration, even when values of these parameters are in the normal range. This is consistent with the hypothesis that chronic activation of the immune system plays a role in the pathogenesis and progression of type 2 diabetes.

Evaluation of a reference material for glycated haemoglobin

NARCIS (Netherlands)

Weykamp, CW; Penders, TJ; Muskiet, FAJ; vanderSlik, W

The use of lyophilized blood as a reference material for glycated haemoglobin was investigated with respect to IFCC criteria for calibrators and control materials. Ninety-two laboratories, using 11 methods, detected no changes in glycated haemoglobin content when the lyophilizate was stored for one

Transcapillary escape rate and relative metabolic clearance of glycated and non-glycated albumin in type 1 (insulin-dependent) diabetes mellitus

DEFF Research Database (Denmark)

Bent-Hansen, L; Feldt-Rasmussen, B; Kverneland, A

1987-01-01

The transcapillary escape rate and relative plasma disappearance of glycated and non-glycated albumin were measured in 25 male Type 1 (insulin-dependent) diabetic patients using a double tracer technique. The patients were divided into three groups on the basis of their urinary albumin excretion......: group 1, normal albumin excretion (less than 30 mg/24 h) (n = 8); group 2, microalbuminuria (30-300 mg/24 h) (n = 9); and group 3, clinical nephropathy (greater than 300 mg/24 h) (n = 8). Six male age-matched non-diabetic persons served as control subjects. The transcapillary escape rate of glycated...... significant role in the development of late diabetic microvascular complications....

Semi-purification procedures of prions from a prion-infected brain using sucrose has no influence on the nonenzymatic glycation of the disease-associated prion isoform.

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Choi, Yeong-Gon; Kim, Jae-Il; Choi, Eun-Kyoung; Carp, Richard I; Kim, Yong-Sun

2016-01-01

Previous studies have shown that the Nε-carboxymethyl group is linked to not only one or more N-terminal Lys residues but also to one or more Lys residues of the protease-resistant core region of the pathogenic prion isoform (PrPSc) in prion-infected brains. Using an anti-advanced glycation end product (AGE) antibody, we detected nonenzymatically glycated PrPSc (AGE-PrPSc) in prion-infected brains following concentration by a series of ultracentrifugation steps with a sucrose cushion. In the present study, the levels of in vitro nonenzymatic glycation of PrPSc using sucrose were investigated to determine whether sucrose cushion can artificially and nonenzymatically induce in vitro glycation during ultracentrifugation. The first insoluble pellet fraction following the first ultracentrifugation (PU1st) collected from 263K scrapie-infected brains was incubated with sucrose, glucose or colloidal silica coated with polyvinylpyrrolidone (percoll). None of the compounds in vitro resulted in AGE-PrPSc. Nonetheless, glucose and percoll produced AGEs in vitro from other proteins within PU1st of the infected brains. This reaction could lead to the AGE-modified polymer(s) of nonenzymatic glycation-prone protein(s). This study showed that PrPSc is not nonenzymatically glycated in vitro with sucrose, glucose or percoll and that AGE-modified PrPSc can be isolated and enriched from prion-infected brains.

Extracellular matrix glycation and receptor for advanced glycation end-products activation: a missing piece in the puzzle of the association between diabetes and cancer.

Science.gov (United States)

Rojas, Armando; Añazco, Carolina; González, Ileana; Araya, Paulina

2018-04-05

A growing body of epidemiologic evidence suggests that people with diabetes are at a significantly higher risk of many forms of cancer. However, the molecular mechanisms underlying this association are not fully understood. Cancer cells are surrounded by a complex milieu, also known as tumor microenvironment, which contributes to the development and metastasis of tumors. Of note, one of the major components of this niche is the extracellular matrix (ECM), which becomes highly disorganized during neoplastic progression, thereby stimulating cancer cell transformation, growth and spread. One of the consequences of chronic hyperglycemia, the most frequently observed sign of diabetes and the etiological source of diabetes complications, is the irreversible glycation and oxidation of proteins and lipids leading to the formation of the advanced glycation end-products (AGEs). These compounds may covalently crosslink and biochemically modify structure and functions of many proteins, and AGEs accumulation is particularly high in long-living proteins with low biological turnover, features that are shared by most, if not all, ECM proteins. AGEs-modified proteins are recognized by AGE-binding proteins, and thus glycated ECM components have the potential to trigger Receptor for advanced glycation end-products-dependent mechanisms. The biological consequence of receptor for advanced glycation end-products activation mechanisms seems to be connected, in different ways, to drive some hallmarks of cancer onset and tumor growth. The present review intends to highlight the potential impact of ECM glycation on tumor progression by triggering receptor for advanced glycation end-products-mediated mechanisms.

A facile route to glycated albumin detection.

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Bohli, Nadra; Meilhac, Olivier; Rondeau, Philippe; Gueffrache, Syrine; Mora, Laurence; Abdelghani, Adnane

2018-07-01

In this paper we propose an easy way to detect the glycated form of human serum albumin which is biomarker for several diseases such as diabetes and Alzheimer. The detection platform is a label free impedimetric immunosensor, in which we used a monoclonal human serum albumin antibody as a bioreceptor and electrochemical impedance as a transducing method. The antibody was deposited onto a gold surface by simple physisorption technique. Bovine serum albumin was used as a blocking agent for non-specific binding interactions. Cyclic voltammetry and electrochemical impedance spectroscopy were used for the characterization of each layer. Human serum albumin was glycated at different levels with several concentrations of glucose ranging from 0 mM to 500 mM representing physiological, pathological (diabetic albumin) and suprapathological concentration of glucose. Through the calibration curves, we could clearly distinguish between two different areas related to physiological and pathological albumin glycation levels. The immunosensor displayed a linear range from 7.49% to 15.79% of glycated albumin to total albumin with a good sensitivity. Surface plasmon resonance imaging was also used to characterize the developed immunosensor. Copyright © 2018 Elsevier B.V. All rights reserved.

Simultaneous estimation of transcutaneous bilirubin, hemoglobin, and melanin based on diffuse reflectance spectroscopy

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Nishidate, Izumi; Abdul, Wares MD.; Ohtsu, Mizuki; Nakano, Kazuya; Haneishi, Hideaki

2018-02-01

We propose a method to estimate transcutaneous bilirubin, hemoglobin, and melanin based on the diffuse reflectance spectroscopy. In the proposed method, the Monte Carlo simulation-based multiple regression analysis for an absorbance spectrum in the visible wavelength region (460-590 nm) is used to specify the concentrations of bilirubin (Cbil), oxygenated hemoglobin (Coh), deoxygenated hemoglobin (Cdh), and melanin (Cm). Using the absorbance spectrum calculated from the measured diffuse reflectance spectrum as a response variable and the extinction coefficients of bilirubin, oxygenated hemoglobin, deoxygenated hemoglobin, and melanin, as predictor variables, multiple regression analysis provides regression coefficients. Concentrations of bilirubin, oxygenated hemoglobin, deoxygenated hemoglobin, and melanin, are then determined from the regression coefficients using conversion vectors that are numerically deduced in advance by the Monte Carlo simulations for light transport in skin. Total hemoglobin concentration (Cth) and tissue oxygen saturation (StO2) are simply calculated from the oxygenated hemoglobin and deoxygenated hemoglobin. In vivo animal experiments with bile duct ligation in rats demonstrated that the estimated Cbil is increased after ligation of bile duct and reaches to around 20 mg/dl at 72 h after the onset of the ligation, which corresponds to the reference value of Cbil measured by a commercially available transcutaneous bilirubin meter. We also performed in vivo experiments with rats while varying the fraction of inspired oxygen (FiO2). Coh and Cdh decreased and increased, respectively, as FiO2 decreased. Consequently, StO2 was dramatically decreased. The results in this study indicate potential of the method for simultaneous evaluation of multiple chromophores in skin tissue.

[Hb Burgos (α1 CD64(E13)(Asp→Asn)): a new hemoglobin variant detected during follow-up of diabetic patients].

Science.gov (United States)

de la Fuente-Gonzalo, Félix; Martínez Nieto, Jorge; Torrejón, María José; Mayor, Luis Antonio; Velasco, Diego; González Fernández, Fernando Ataulfo; Ropero Gradilla, Paloma

2015-01-06

The glycated hemoglobin (HbA1c) test by high performance liquid chromatography is a useful tool for the follow-up of diabetes mellitus patients. Some structural hemoglobin (Hb) variants are known to cause interference in the analytical measurement of HbA1c. In this study, it has been characterized a new Hb variant in 4 patients during their regular control of HbA1c. Selective α1 gene sequencing showed a mutation GAC>AAC at codon 64 within exon 2. This produces a change of aspartic acid (Asp) by asparagine (Asn) that does not produce any functional alteration so the resultant molecule behaves as a silent hemoglobinopathy. The structural Hb variants can be detected during the analysis of HbA1c and may alter its values. Though rare, this occurrence signals the need to being aware when measuring HbA1c. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

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

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

2013-01-01

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

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

Directory of Open Access Journals (Sweden)

Peng Chen

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

Spin Label Studies of the Hemoglobin-Membrane Interaction During Sickle Hemoglobin Polymerization

International Nuclear Information System (INIS)

Falcon Dieguez, Jose E.; Rodi, Pablo; Lores Guevara, Manuel A.; Gennaro, Ana Maria

2009-12-01

An enhanced hemoglobin-membrane association has been previously documented in Sickle Cell Anemia. However, it is not known how this interaction is modified during the hemoglobin S polymerization process. In this work, we use a model of reconstituted erythrocytes from ghost membranes whose cytoskeleton proteins had been previously labeled with the 4-maleimido Tempo spin label, and that were subsequently resealed with hemoglobin S or A solutions. Using EPR spectroscopy, we studied the time dependence of the spectral W/S parameter, indicative of the conformational state of cytoskeleton proteins (mainly spectrin) under spontaneous deoxygenation, with the aim of detecting the eventual effects due to hemoglobin S polymerization. The differences observed in the temporal behaviour of W/S in erythrocytes reconstituted with both hemoglobins were considered as experimental evidence of an increment in hemoglobin S-membrane interaction, as a result of the polymerization process of hemoglobin S under spontaneous deoxygenation. (author)

Hemoglobin (image)

Science.gov (United States)

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 ...

Glycation alters ligand binding, enzymatic, and pharmacological properties of human albumin.

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Baraka-Vidot, Jennifer; Planesse, Cynthia; Meilhac, Olivier; Militello, Valeria; van den Elsen, Jean; Bourdon, Emmanuel; Rondeau, Philippe

2015-05-19

Albumin, the major circulating protein in blood plasma, can be subjected to an increased level of glycation in a diabetic context. Albumin exerts crucial pharmacological activities through its drug binding capacity, i.e., ketoprofen, and via its esterase-like activity, allowing the conversion of prodrugs into active drugs. In this study, the impact of the glucose-mediated glycation on the pharmacological and biochemical properties of human albumin was investigated. Aggregation product levels and the redox state were quantified to assess the impact of glycation-mediated changes on the structural properties of albumin. Glucose-mediated changes in ketoprofen binding properties and esterase-like activity were evaluated using fluorescence spectroscopy and p-nitrophenyl acetate hydrolysis assays, respectively. With the exception of oxidative parameters, significant dose-dependent alterations in biochemical and functional properties of in vitro glycated albumin were observed. We also found that the dose-dependent increase in levels of glycation and protein aggregation and average molecular mass changes correlated with a gradual decrease in the affinity of albumin for ketoprofen and its esterase-like property. In parallel, significant alterations in both pharmacological properties were also evidenced in albumin purified from diabetic patients. Partial least-squares regression analyses established a significant correlation between glycation-mediated changes in biochemical and pharmacological properties of albumin, highlighting the important role for glycation in the variability of the drug response in a diabetic situation.

Diagnostic Accuracies of Glycated Hemoglobin, Fructosamine, and Homeostasis Model Assessment of Insulin Resistance in Predicting Impaired Fasting Glucose, Impaired Glucose Tolerance, or New Onset Diabetes After Transplantation.

Science.gov (United States)

Rosettenstein, Kerri; Viecelli, Andrea; Yong, Kenneth; Nguyen, Hung Do; Chakera, Aron; Chan, Doris; Dogra, Gursharan; Lim, Ee Mun; Wong, Germaine; Lim, Wai H

2016-07-01

New onset diabetes after transplantation (NODAT) is associated with a 3-fold greater risk of cardiovascular disease events, with early identification and treatment potentially attenuating this risk. The optimal screening test to identify those with NODAT remains unclear, and the aim of this study was to examine the diagnostic accuracies of 4 screening tests in identifying impaired fasting glucose, impaired glucose tolerance (IGT), and NODAT. This is a single-center prospective cohort study of 83 nondiabetic kidney transplant recipients between 2008 and 2011. Oral glucose tolerance test was considered the gold standard in identifying IFG/IGT or NODAT. Diagnostic accuracies of random blood glucose, glycated hemoglobin (HBA1c), fructosamine, and Homeostasis Model Assessment-Insulin Resistance in predicting IFG/IGT or NODAT were assessed using the area under the receiver operating characteristic curve. Forty (48%) recipients had IFG/IGT or NODAT. Compared with HBA1c with adjusted area under the curve (AUC) of 0.88 (95% confidence interval [95% CI], 0.77-0.93), fructosamine was the most accurate test with adjusted AUC of 0.92 (95% CI, 0.83-0.96). The adjusted AUCs of random blood glucose and Homeostasis Model Assessment-Insulin Resistance in identifying IFG/IGT were between 0.81 and 0.85. Restricting to identifying IGT/NODAT using 2-hour oral glucose tolerance test (n = 66), fructosamine was the most accurate diagnostic test with adjusted AUC of 0.93 (95% CI, 0.84-0.99), but not statistically different to HBA1c with adjusted AUC of 0.88 (95% CI, 0.76-0.96). Although HBA1c is an acceptable and widely used screening test in detecting IFG/IGT or NODAT, fructosamine may be a more accurate diagnostic test but this needs to be further examined in larger cohorts.

Oncocalyxone A functions as an anti-glycation agent in vitro.

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Ingrid Sofia Vieira de Melo

Full Text Available Advanced glycation endproducts (AGE are the result of post-translational changes to proteins, which ultimately compromise their structure and/or function. The identification of methods to prevent the formation of these compounds holds great promise in the development of alternative therapies for diseases such as diabetes. Plants used in traditional medicine are often rich sources of anti-glycation agents. Therefore, in this study, we investigated the anti-glycation activity of one such compound, Oncocalyxone A (Onco A. Using spectrofluorimetric techniques, we determined that Onco A inhibits AGE formation in a concentration-dependent manner. Its IC50 value (87.88 ± 3.08 μM was almost two times lower than the standard anti-glycation compound aminoguanidine (184.68 ± 4.85 μM. The excellent anti-glycation activity of Onco A makes it an exciting candidate for the treatment of diseases associated with excessive accumulation of AGE. However, additional studies are necessary to identify its mechanism of action, as well as the in vivo response in suitable model organisms.

Glycation induces formation of amyloid cross-beta structure in albumin.

Science.gov (United States)

Bouma, Barend; Kroon-Batenburg, Loes M J; Wu, Ya-Ping; Brünjes, Bettina; Posthuma, George; Kranenburg, Onno; de Groot, Philip G; Voest, Emile E; Gebbink, Martijn F B G

2003-10-24

Amyloid fibrils are components of proteinaceous plaques that are associated with conformational diseases such as Alzheimer's disease, transmissible spongiform encephalopathies, and familial amyloidosis. Amyloid polypeptides share a specific quarternary structure element known as cross-beta structure. Commonly, fibrillar aggregates are modified by advanced glycation end products (AGE). In addition, AGE formation itself induces protein aggregation. Both amyloid proteins and protein-AGE adducts bind multiligand receptors, such as receptor for AGE, CD36, and scavenger receptors A and B type I, and the serine protease tissue-type plasminogen activator (tPA). Based on these observations, we hypothesized that glycation induces refolding of globular proteins, accompanied by formation of cross-beta structure. Using transmission electron microscopy, we demonstrate here that glycated albumin condensates into fibrous or amorphous aggregates. These aggregates bind to amyloid-specific dyes Congo red and thioflavin T and to tPA. In contrast to globular albumin, glycated albumin contains amino acid residues in beta-sheet conformation, as measured with circular dichroism spectropolarimetry. Moreover, it displays cross-beta structure, as determined with x-ray fiber diffraction. We conclude that glycation induces refolding of initially globular albumin into amyloid fibrils comprising cross-beta structure. This would explain how glycated ligands and amyloid ligands can bind to the same multiligand "cross-beta structure" receptors and to tPA.

The impact of prematurity on fetal haemoglobin and how it can bias measurement of glycated haemoglobin

DEFF Research Database (Denmark)

Zachariassen, Gitte; Esberg, Gitte; Grytter, Carl

Background: The extent to which fetal hemoglobin (HbF) concentrations are increased in premature infants at the age of six to eight months is only sporadically described. The influence of HbF on measurement of glycated haemoglobin (HbA1c) has not been investigated in this population. Methods......: As part of a nutritional study on premature children, HbF and HbA1c were measured in 46 premature infants at the age of six to eight months. Results: Median HbF percentage was 10.3% (range 2.0 to 39.2%). In a multiple regression model only birth weight (P = 0.002) and post-conceptional age (P ... significantly from unadjusted values (4.4±0.4%), (P premature infants at six to eight months of age. The clinical implication of this work is a renewed attention on the prolonged Hb...

Destructive effect of non-enzymatic glycation on catalase and remediation via curcumin.

Science.gov (United States)

Mofidi Najjar, Fayezeh; Taghavi, Fereshteh; Ghadari, Rahim; Sheibani, Nader; Moosavi-Movahedi, Ali Akbar

2017-09-15

Non-enzymatic glycation of proteins is a post-translational modification that is produced by a covalent binding between reducing sugars and amino groups of lysine and arginine residues. In this paper the effect of pathological conditions, derived from hyperglycemia on bovine liver catalase (BLC) as a model protein was considered by measuring enzyme activity, reactive oxygen species (ROS) generation, and changes in catalase conformational properties. We observed that in the presence of glucose, the catalase activity gradually decreased. ROS generation was also involved in the glycation process. Thus, decreased BLC activity was partly considered as a result of ROS generation through glycation. However, in the presence of curcumin the amount of ROS was reduced resulting in increased activity of the glycated catalase. The effect of high glucose level and the potential inhibitory effect of curcumin on aggregation and structural changes of catalase were also investigated. Molecular dynamic simulations also showed that interaction of catalase with curcumin resulted in changes in accessible surface area (ASA) and pKa, two effective parameters of glycation, in potential glycation lysine residues. Thus, the decrease in ASA and increase in pKa of important lysine residues were considered as predominant factors in decreased glycation of BLC by curcumin. Copyright © 2017 Elsevier Inc. All rights reserved.

Dysfunctional lipoproteins from young smokers exacerbate cellular senescence and atherogenesis with smaller particle size and severe oxidation and glycation.

Science.gov (United States)

Park, Ki-Hoon; Shin, Dong-Gu; Cho, Kyung-Hyun

2014-07-01

Until now, there has been limited information on the effects of smoking on atherogenesis and senescence in the context of lipoprotein parameters, particularly in young smokers who have smoked fewer than 10 cigarettes per day for 3 years. In this study, lipoprotein profiles and functions were compared between smoker (n = 21) and control groups (n = 20). In the smoking group, ferric ion reduction abilities of serum and high-density lipoprotein (HDL) fractions were significantly reduced, and low-density lipoprotein (LDL) was severely oxidized. All lipoprotein particles from the smoker group showed higher advanced glycated end products with more triglyceride (TG) content compared with the control group. Lipoproteins from smokers showed faster agarose gel electromobility as well as greater smear band intensity in SDS-PAGE due to oxidation and glycation. LDL from smokers was more sensitive to oxidation and promoted foam cell forma-tion in macrophages. Gel filtration column chromatography revealed that the protein and cholesterol peaks of VLDL and LDL were elevated in the smoker group, whereas those of HDL were reduced. Human dermal fibroblast cells from the smoker group showed severe senescence following treatment with HDL2 and HDL3. Although HDL from young smokers showed impaired antioxidant ability, smaller particle size, and increased TG content, cholesteryl ester transfer protein activities were greatly enhanced in the serum and HDL fractions of the smoker group. In conclusion, smoking can cause production of dysfunctional lipoproteins having a smaller particle size that exacerbate senescence and atherogenic progress due to oxidation and glycation. © The Author 2014. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Calorimetric investigation of diclofenac drug binding to a panel of moderately glycated serum albumins.

Science.gov (United States)

Indurthi, Venkata S K; Leclerc, Estelle; Vetter, Stefan W

2014-08-01

Glycation alters the drug binding properties of serum proteins and could affect free drug concentrations in diabetic patients with elevated glycation levels. We investigated the effect of bovine serum albumin glycation by eight physiologically relevant glycation reagents (glucose, ribose, carboxymethyllysine, acetoin, methylglyoxal, glyceraldehyde, diacetyl and glycolaldehyde) on diclofenac drug binding. We used this non-steroidal anti-inflammatory drug diclofenac as a paradigm for acidic drugs with high serum binding and because of its potential cardiovascular risks in diabetic patients. Isothermal titration calorimetry showed that glycation reduced the binding affinity Ka of serum albumin and diclofenac 2 to 6-fold by reducing structural rigidity of albumin. Glycation affected the number of drug binding sites in a glycation reagent dependent manner and lead to a 25% decrease for most reagent, expect for ribose, with decreased by 60% and for the CML-modification, increased the number of binding sites by 60%. Using isothermal titration calorimetry and differential scanning calorimetry we derived the complete thermodynamic characterization of diclofenac binding to all glycated BSA samples. Our results suggest that glycation in diabetic patients could significantly alter the pharmacokinetics of the widely used over-the-counter NSDAI drug diclofenac and with possibly negative implications for patients. Copyright © 2014 Elsevier B.V. All rights reserved.

Products by Glycation Process

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Liliana Ortega

2015-01-01

Full Text Available The antioxidant properties of sweet and acid whey products were incremented by polymerization of their proteins by glycation of whey protein concentrates (WPC and their hydrolyzates (WPCH with ribose and glucose in individual experiments under similar concentration. Heating at 50°C during 20 h maximum and pH 7 and pH 9 were used in all tests. The higher activity was found in WPC glycosylates products with ribose at pH 7 and heating during 10–15 h. In comparable form, antioxidant activity in WPCH was incremented by prior hydrolysis to glycation with 25–45% of hydrolysis degree. Further functional properties of whey proteins (solubility, emulsion, and foam were also improved by the polymerization with ribose. The color of polymerized products due to Maillard reactions was associated with antioxidant activity of each compound; however comparative color in glycosylates products with glucose and ribose did not show this effect.

No effect of the hemoglobin solution HBOC-201 on the response of the rat R1H tumor to fractionated irradiation

International Nuclear Information System (INIS)

Raabe, A.

2005-01-01

Background and Purpose: Tumor hypoxia is regarded as one important underlying feature of radioresistance. The authors report on an experimental approach to improve tumor response to radiation by combining fractionated irradiation with HBOC-201, an ultrapurified polymerized hemoglobin solution, which is currently used in clinical phase II/III trials as alternative oxygen carrier and proved to be highly effective in tissue oxygenation (tpO 2 ). Material and Methods: Subcutaneously growing rhabdomyosarcoma R1H tumors of the rat were treated with either 40 Gy (2 Gy/fraction, 20 fractions in 2 weeks, ambient) followed by grade top-up doses (clamped) alone, or in combination with HBOC-201, or with HBOC-201 plus carbogen (95% O 2 +5% CO 2 ). Local tumor control (TCD50%) and growth delay were used as endpoints. In addition, the effect of HBOC-201 alone or in combination with carbogen on the tpO 2 of tumor and muscle was determined using a flexible stationary probe (Licox, GMS). Results: TCD50% values of 119 Gy (95% confidence interval 103; 135), 111 Gy (84; 138), and 102 Gy (83; 120) were determined for tumors irradiated alone, in combination with HBOC-201, and with HBOC-201 plus carbogen, respectively. Although the dose-response curves showed a slight shift to lower doses when HBOC-201 or HBOC-201 plus carbogen was added, the differences in TCD50% were not statistically significant. No effect was seen on the growth delay of recurrent tumors. HBOC-201 alone did not effect tumor or muscle tpO 2 . In combination with carbogen the mean tpO 2 muscle raised from 23.9 mmHg to 59.3 mmHg (p 2 by carbogen alone. Conclusion: Low-dose application of HBOC-201 does not improve the response of the rhabdomyosarcoma R1H of the rat to fractionated irradiation. (orig.)

No effect modification of serum bilirubin or coffee consumption on the association of gamma-glutamyltransferase with glycated hemoglobin in a cross-sectional study of Japanese men and women

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Wang Zhenjie

2012-10-01

Full Text Available Abstract Background Oxidative stress has been implicated in the development of type 2 diabetes mellitus. Bilirubin is a potent endogenous antioxidant, and coffee is a major source of exogenous antioxidants. Serum gamma-glutamyltransferase (GGT, a marker of oxidative stress, is a strong predictor of the risk of type 2 diabetes mellitus. This study evaluated the effect modification of bilirubin and coffee consumption on the association of serum GGT with glycated hemoglobin (HbA1c and the combined effect of bilirubin and coffee on HbA1c concentrations. Methods The subjects were 4492 men and 6242 women aged 49–76 years who participated in the baseline survey of an on-going cohort study on lifestyle-related diseases in Fukuoka, Japan. Geometric means of HbA1c were examined according to quartile categories of GGT, with stratification by serum total bilirubin (≥ 0.6 mg/dL versus less in men and ≥ 0.5 mg/dL versus less in women and coffee consumption ( Results HbA1 concentrations increased progressively with increasing levels of GGT in both men and women. The increasing trend of HbA1c concentrations associated with GGT did not differ by either bilirubin status or coffee consumption. Both men and women with high bilirubin had consistently lower concentrations of HbA1c across the GGT quartiles. Higher coffee consumption was associated with lower concentrations of HbA1c in women with low bilirubin (trend P = 0.04, but not with high bilirubin (trend P = 0.37. There was no such association between coffee and HbA1c in men with either low or high bilirubin levels. Conclusions Bilirubin is possibly protective against deterioration of glucose metabolism. Further studies are needed regarding the combined effect of bilirubin and coffee on glucose metabolism.

Age estimation of blood stains by hemoglobin derivative determination using reflectance spectroscopy

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Bremmer, Rolf H.; Nadort, Annemarie; van Leeuwen, Ton G.; van Gemert, Martin J. C.; Aalders, Maurice C. G.

2011-01-01

Blood stains can be crucial in reconstructing crime events. However, no reliable methods are currently available to establish the age of a blood stain on the crime scene. We show that determining the fractions of three hemoglobin derivatives in a blood stain at various ages enables relating these

Radioimmunochemical characterization of hemoglobins Lepore and Kenya: unique antigenic determinants located on hybrid hemoglobins

International Nuclear Information System (INIS)

Garver, F.A.; Altay, G.; Baker, M.M.; Gravely, M.; Huisman, T.H.J.

1978-01-01

Antisera were produced in rabbits to the three known types of Lepore hemoglobins, which contain hybrid delta-β non-α-chains, and to hemoglobin Kenya, which has a hybrid γ-β non-α-chain. By using a sensitive radioimmunoassay technique, the absorbed antisera were shown to contain an antibody population that was specific for the hybrid hemoglobin and did not cross-react with normal hemoglobins. However, with the absorbed Lepore-specific antisera, the three known types of Lepore hemoglobins were antigenically indistinguishable from each other, suggesting that antibodies are not produced to the primary structural differences which define the three non-α-chains of the Lepore hemoglobins. These studies demonstrate that the non-α-subunits of hemoglobins Lepore and Kenya possess unique antigenic determinant sites, evidently resulting from an altered polypeptide conformation

Biphasic oxidation of oxy-hemoglobin in bloodstains.

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Rolf H Bremmer

Full Text Available BACKGROUND: In forensic science, age determination of bloodstains can be crucial in reconstructing crimes. Upon exiting the body, bloodstains transit from bright red to dark brown, which is attributed to oxidation of oxy-hemoglobin (HbO(2 to met-hemoglobin (met-Hb and hemichrome (HC. The fractions of HbO(2, met-Hb and HC in a bloodstain can be used for age determination of bloodstains. In this study, we further analyze the conversion of HbO(2 to met-Hb and HC, and determine the effect of temperature and humidity on the conversion rates. METHODOLOGY: The fractions of HbO(2, met-Hb and HC in a bloodstain, as determined by quantitative analysis of optical reflectance spectra (450-800 nm, were measured as function of age, temperature and humidity. Additionally, Optical Coherence Tomography around 1300 nm was used to confirm quantitative spectral analysis approach. CONCLUSIONS: The oxidation rate of HbO(2 in bloodstains is biphasic. At first, the oxidation of HbO(2 is rapid, but slows down after a few hours. These oxidation rates are strongly temperature dependent. However, the oxidation of HbO(2 seems to be independent of humidity, whereas the transition of met-Hb into HC strongly depends on humidity. Knowledge of these decay rates is indispensable for translating laboratory results into forensic practice, and to enable bloodstain age determination on the crime scene.

Inhibitory effect of alliin from Allium sativum on the glycation of superoxide dismutase.

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Anwar, Shehwaz; Younus, Hina

2017-10-01

Inhibition of glycation is an important approach for alleviating diabetic complications. Alliin, the most abundant sulphur compound in garlic has been demonstrated to possess antidiabetic activity. However, there is no scientific evidence supporting its antiglycating activity. The objective of this study was to determine the inhibitory effect of alliin on glucose and methyglyoxal (MG)-induced glycation of an important antioxidant enzyme, superoxide dismutase (SOD). Glycation of SOD resulted in a decrease in enzyme activity, fragmentation/cross-linking, reduced cross-reactivity with anti-SOD antibodies, both tertiary and secondary structural changes, and formation of AGEs and fibrils. Alliin offered protection against glucose or MG induced glycation of SOD. The antiglycating potential of alliin appears to be comparable with that of quercetin which is reported to be a potent natural inhibitor of glycation. Alliin has a good antiglycating effect and hence is expected to have therapeutic potential in the prevention of glycation-mediated diabetic complications. Copyright © 2017 Elsevier B.V. All rights reserved.

The effects of 2,3-diphosphoglycerate, adenosine triphosphate, and glycosylated hemoglobin on the hemoglobin-oxygen affinity of diabetic patients

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Castilho E.M.

2003-01-01

Full Text Available The position of the oxygen dissociation curve (ODC is modulated by 2,3-diphosphoglycerate (2,3-DPG. Decreases in 2,3-DPG concentration within the red cell shift the curve to the left, whereas increases in concentration cause a shift to the right of the ODC. Some earlier studies on diabetic patients have reported that insulin treatment may reduce the red cell concentrations of 2,3-DPG, causing a shift of the ODC to the left, but the reports are contradictory. Three groups were compared in the present study: 1 nondiabetic control individuals (N = 19; 2 insulin-dependent diabetes mellitus (IDDM patients (on insulin treatment (N = 19; 3 non-insulin-dependent diabetes mellitus (NIDDM patients using oral hypoglycemic agents and no insulin treatment (N = 22. The overall position of the ODC was the same for the three groups despite an increase of the glycosylated hemoglobin fraction that was expected to shift the ODC to the left in both groups of diabetic patients (HbA1c: control, 4.6%; IDDM, 10.5%; NIDDM, 9.0%. In IDDM patients, the effect of the glycosylated hemoglobin fraction on the position of the ODC appeared to be counterbalanced by small though statistically significant increases in 2,3-DPG concentration from 2.05 (control to 2.45 µmol/ml blood (IDDM. Though not statistically significant, an increase of 2,3-DPG also occurred in NIDDM patients, while red cell ATP levels were the same for all groups. The positions of the ODC were the same for control subjects, IDDM and NIDDM patients. Thus, the PO2 at 50% hemoglobin-oxygen saturation was 26.8, 28.2 and 28.5 mmHg for control, IDDM and NIDDM, respectively. In conclusion, our data question the idea of adverse side effects of insulin treatment on oxygen transport. In other words, the shift to the left reported by others to be caused by insulin treatment was not detected.

The effects of 2,3-diphosphoglycerate, adenosine triphosphate, and glycosylated hemoglobin on the hemoglobin-oxygen affinity of diabetic patients.

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Castilho, E M; Glass, M L; Manço, J C

2003-06-01

The position of the oxygen dissociation curve (ODC) is modulated by 2,3-diphosphoglycerate (2,3-DPG). Decreases in 2,3-DPG concentration within the red cell shift the curve to the left, whereas increases in concentration cause a shift to the right of the ODC. Some earlier studies on diabetic patients have reported that insulin treatment may reduce the red cell concentrations of 2,3-DPG, causing a shift of the ODC to the left, but the reports are contradictory. Three groups were compared in the present study: 1) nondiabetic control individuals (N = 19); 2) insulin-dependent diabetes mellitus (IDDM) patients (on insulin treatment) (N = 19); 3) non-insulin-dependent diabetes mellitus (NIDDM) patients using oral hypoglycemic agents and no insulin treatment (N = 22). The overall position of the ODC was the same for the three groups despite an increase of the glycosylated hemoglobin fraction that was expected to shift the ODC to the left in both groups of diabetic patients (HbA1c: control, 4.6%; IDDM, 10.5%; NIDDM, 9.0%). In IDDM patients, the effect of the glycosylated hemoglobin fraction on the position of the ODC appeared to be counterbalanced by small though statistically significant increases in 2,3-DPG concentration from 2.05 (control) to 2.45 mol/ml blood (IDDM). Though not statistically significant, an increase of 2,3-DPG also occurred in NIDDM patients, while red cell ATP levels were the same for all groups. The positions of the ODC were the same for control subjects, IDDM and NIDDM patients. Thus, the PO2 at 50% hemoglobin-oxygen saturation was 26.8, 28.2 and 28.5 mmHg for control, IDDM and NIDDM, respectively. In conclusion, our data question the idea of adverse side effects of insulin treatment on oxygen transport. In other words, the shift to the left reported by others to be caused by insulin treatment was not detected.

Fish hemoglobins

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P.C. de Souza

2007-06-01

Full Text Available Vertebrate hemoglobin, contained in erythrocytes, is a globular protein with a quaternary structure composed of 4 globin chains (2 alpha and 2 beta and a prosthetic group named heme bound to each one. Having myoglobin as an ancestor, hemoglobin acquired the capacity to respond to chemical stimuli that modulate its function according to tissue requirements for oxygen. Fish are generally submitted to spatial and temporal O2 variations and have developed anatomical, physiological and biochemical strategies to adapt to the changing environmental gas availability. Structurally, most fish hemoglobins are tetrameric; however, those from some species such as lamprey and hagfish dissociate, being monomeric when oxygenated and oligomeric when deoxygenated. Fish blood frequently possesses several hemoglobins; the primary origin of this finding lies in the polymorphism that occurs in the globin loci, an aspect that may occasionally confer advantages to its carriers or even be a harmless evolutionary remnant. On the other hand, the functional properties exhibit different behaviors, ranging from a total absence of responses to allosteric regulation to drastic ones, such as the Root effect.

Coptis chinensis Polysaccharides Inhibit Advanced Glycation End Product Formation.

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Yang, Ye; Li, Yun; Yin, Dengke; Chen, Song; Gao, Xiangdong

2016-06-01

Coptis chinensis Franch (Huanglian) is commonly used to treat diabetes in China. In this study, the effects of the C. chinensis Franch polysaccharides (CCP) on advanced glycation end product (AGE) formation in vitro and in streptozotocin-induced diabetic mice were investigated. CCP significantly inhibited all the three periods of nonenzymatic protein glycation in vitro, including Amadori product, dicarbonyl compound, and AGE formation (P < .01). In diabetic mice, the administration of CCP not only improved both bodyweight and serum insulin and decreased fasting blood glucose and glycated serum protein concentrations but also decreased the AGE accumulations and morphological abnormalities in pancreas and liver. The inhibitory effects of CCP on AGE formation afford a potential therapeutic use in the prevention and treatment of diabetes.

Alpha chain hemoglobins with electrophoretic mobility similar to that of hemoglobin S in a newborn screening program.

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Silva, Marcilene Rezende; Sendin, Shimene Mascarenhas; Araujo, Isabela Couto de Oliveira; Pimentel, Fernanda Silva; Viana, Marcos Borato

2013-01-01

To characterize alpha-chain variant hemoglobins with electric mobility similar to that of hemoglobin S in a newborn screening program. β(S) allele and alpha-thalassemia deletions were investigated in 14 children who had undefined hemoglobin at birth and an electrophoretic profile similar to that of hemoglobin S when they were six months old. Gene sequencing and restriction enzymes (DdeI, BsaJI, NlaIV, Bsu36I and TaqI) were used to identify hemoglobins. Clinical and hematological data were obtained from children who attended scheduled medical visits. THE FOLLOWING ALPHA CHAIN VARIANTS WERE FOUND: seven children with hemoglobin Hasharon [alpha2 47(CE5) Asp>His, HbA2:c.142G>C], all associated with alpha-thalassemia, five with hemoglobin Ottawa [alpha1 15(A13) Gly>Arg, HBA1:c.46G>C], one with hemoglobin St Luke's [alpha1 95(G2) Pro>Arg, HBA1:c.287C>G] and another one with hemoglobin Etobicoke [alpha212 84(F5) Ser>Arg, HBA212:c.255C>G]. Two associations with hemoglobin S were found: one with hemoglobin Ottawa and one with hemoglobin St Luke's. The mutation underlying hemoglobin Etobicoke was located in a hybrid α212 allele in one child. There was no evidence of clinically relevant hemoglobins detected in this study. Apparently these are the first cases of hemoglobin Ottawa, St Luke's, Etobicoke and the α212 gene described in Brazil. The hemoglobins detected in this study may lead to false diagnosis of sickle cell trait or sickle cell disease when only isoelectric focusing is used in neonatal screening. Additional tests are necessary for the correct identification of hemoglobin variants.

Detection of Sickle Cell Hemoglobin in Haiti by Genotyping and Hemoglobin Solubility Tests

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Carter, Tamar E.; von Fricken, Michael; Romain, Jean R.; Memnon, Gladys; St. Victor, Yves; Schick, Laura; Okech, Bernard A.; Mulligan, Connie J.

2014-01-01

Sickle cell disease is a growing global health concern because infants born with the disorder in developing countries are now surviving longer with little access to diagnostic and management options. In Haiti, the current state of sickle cell disease/trait in the population is unclear. To inform future screening efforts in Haiti, we assayed sickle hemoglobin mutations using traditional hemoglobin solubility tests (HST) and add-on techniques, which incorporated spectrophotometry and insoluble hemoglobin separation. We also generated genotype data as a metric for HST performance. We found 19 of 202 individuals screened with HST were positive for sickle hemoglobin, five of whom did not carry the HbS allele. We show that spectrophotometry and insoluble hemoglobin separation add-on techniques could resolve false positives associated with the traditional HST approach, with some limitations. We also discuss the incorporation of insoluble hemoglobin separation observation with HST in suboptimal screening settings like Haiti. PMID:24957539

Effect of Temperature on Tolbutamide Binding to Glycated Serum Albumin

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Agnieszka Szkudlarek

2017-03-01

Full Text Available Glycation process occurs in protein and becomes more pronounced in diabetes when an increased amount of reducing sugar is present in bloodstream. Glycation of protein may cause conformational changes resulting in the alterations of its binding properties even though they occur at a distance from the binding sites. The changes in protein properties could be related to several pathological consequences such as diabetic and nondiabetic cardiovascular diseases, cataract, renal dysfunction and Alzheimer’s disease. The experiment was designed to test the impact of glycation process on sulfonylurea drug tolbutamide-albumin binding under physiological (T = 309 K and inflammatory (T = 311 K and T = 313 K states using fluorescence and UV-VIS spectroscopies. It was found in fluorescence analysis experiments that the modification of serum albumin in tryptophanyl and tyrosyl residues environment may affect the tolbutamide (TB binding to albumin in subdomain IIA and/or IIIA (Sudlow’s site I and/or II, and also in subdomains IB and IIB. We estimated the binding of tolbutamide to albumin described by a mixed nature of interaction (specific and nonspecific. The association constants Ka (L∙mol−1 for tolbutamide at its high affinity sites on non-glycated albumin were in the range of 1.98–7.88 × 104 L∙mol−1 (λex = 275 nm, 1.20–1.64 × 104 L∙mol−1 (λex = 295 nm and decreased to 1.24–0.42 × 104 L∙mol−1 at λex = 275 nm (T = 309 K and T = 311 K and increased to 2.79 × 104 L∙mol−1 at λex = 275 nm (T = 313 K and to 4.43–6.61 × 104 L∙mol−1 at λex = 295 nm due to the glycation process. Temperature dependence suggests the important role of van der Waals forces and hydrogen bonding in hydrophobic interactions between tolbutamide and both glycated and non-glycated albumin. We concluded that the changes in the environment of TB binding of albumin in subdomain IIA and/or IIIA as well as in subdomains IB and IIB influence on

Serum glycated albumin as a new glycemic marker in pediatric diabetes

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Ji Woo Lee

2013-12-01

Full Text Available PurposeSerum glycated albumin (GA has been recently used as another glycemic marker that reflects shorter term glycemic control than glycated hemoglobin (HbA1c. Insulin secretory function and glycemic fluctuation might be correlated with the ratio of GA to HbA1c (GA/HbA1c in diabetic adult patients. This study investigated the association of GA and GA/HbA1c ratio with the levels of fasting C-peptide, fasting plasma glucose in type 1 and type 2 pediatric diabetes.MethodsTotal 50 cases from 42 patients were included. The subjects were classified into type 1 diabetes mellitus (T1DM (n=30 and type 2 diabetes mellitus (T2DM (n=20 group. The associations among HbA1c, GA, and GA/HbA1c ratio were examined. The relationship between the three glycemic indices and fasting glucose, fasting C-peptide were analyzed.ResultsMean values of GA, the GA/HbA1c ratio were significantly higher in T1DM than T2DM. GA (r=0.532, P=0.001, HbA1c (r=0.519, P=0.002 and the GA/HbA1c ratio (r=0.409, P=0.016 were correlated with the fasting plasma glucose. Fasting C-peptide level arranged 4.22±3.22 ng/mL in T2DM, which was significantly above the values in T1DM (0.26±0.49 ng/mL. There were no significant correlation between HbA1c and fasting C-peptide level. However, GA and the GA/HbA1c ratio exhibited inverse correlations with fasting C-peptide level (r=-0.214, P=0.002; r=-0.516, P<0.001.ConclusionGA seems to more accurately reflects fasting plasma glucose level than HbA1c. GA, GA/HbA1c ratio appear to reflect insulin secretory function.

Glycation of polyclonal IgGs: Effect of sugar excipients during stability studies.

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Leblanc, Y; Bihoreau, N; Jube, M; Andre, M-H; Tellier, Z; Chevreux, G

2016-05-01

A number of intravenous immunoglobulin preparations are stabilized with sugar additives that may lead over time to undesirable glycation reactions especially in liquid formulation. This study aimed to evaluate the reactivity of sugar excipients on such preparations in condition of temperature, formulation and concentration commonly used for pharmaceutical products. Through an innovative LC-MS method reported to characterize post-translational modifications of IgGs Fc/2 fragments, a stability study of IVIg formulated with reducing and non-reducing sugars has been undertaken. The rate of polyclonal IgGs glycation was investigated during 6months at 5, 25, 30 and 40°C. High levels of glycation were observed with reducing sugars such as glucose and maltose in the first months of the stability study from 25°C. Non-reducing sugars presented a low reactivity even at the highest tested temperature (40°C). Furthermore, a site by site analysis was performed by MS/MS to determine the glycation sites which were mainly identified at Lys246, Lys248 and Lys324. This work points out the high probability of glycation reactions in some commercialized products and describes a useful method to characterize IVIg glycated products issued from reducing sugar excipients. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Alpha chain hemoglobins with electrophoretic mobility similar to that of hemoglobin S in a newborn screening program

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Marcilene Rezende Silva

2013-01-01

Full Text Available OBJECTIVE: To characterize alpha-chain variant hemoglobins with electric mobility similar to that of hemoglobin S in a newborn screening program. METHODS: βS allele and alpha-thalassemia deletions were investigated in 14 children who had undefined hemoglobin at birth and an electrophoretic profile similar to that of hemoglobin S when they were six months old. Gene sequencing and restriction enzymes (DdeI, BsaJI, NlaIV, Bsu36I and TaqI were used to identify hemoglobins. Clinical and hematological data were obtained from children who attended scheduled medical visits. RESULTS: The following alpha chain variants were found: seven children with hemoglobin Hasharon [alpha2 47(CE5 Asp>His, HbA2:c.142G>C], all associated with alpha-thalassemia, five with hemoglobin Ottawa [alpha1 15(A13 Gly>Arg, HBA1:c.46G>C], one with hemoglobin St Luke's [alpha1 95(G2 Pro>Arg, HBA1:c.287C>G] and another one with hemoglobin Etobicoke [alpha212 84(F5 Ser>Arg, HBA212:c.255C>G]. Two associations with hemoglobin S were found: one with hemoglobin Ottawa and one with hemoglobin St Luke's. The mutation underlying hemoglobin Etobicoke was located in a hybrid α212 allele in one child. There was no evidence of clinically relevant hemoglobins detected in this study. CONCLUSION: Apparently these are the first cases of hemoglobin Ottawa, St Luke's, Etobicoke and the α212 gene described in Brazil. The hemoglobins detected in this study may lead to false diagnosis of sickle cell trait or sickle cell disease when only isoelectric focusing is used in neonatal screening. Additional tests are necessary for the correct identification of hemoglobin variants.

Antioxidant, anti-glycation and anti-inflammatory activities of phenolic constituents from Cordia sinensis.

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Al-Musayeib, Nawal; Perveen, Shagufta; Fatima, Itrat; Nasir, Muhammad; Hussain, Ajaz

2011-12-08

Nine compounds have been isolated from the ethyl acetate soluble fraction of C. sinensis, namely protocatechuic acid (1), trans-caffeic acid (2), methyl rosmarinate (3), rosmarinic acid (4), kaempferide-3-O-β-D-glucopyranoside (5), kaempferol-3-O-β-D-glucopyranoside (6), quercetin-3-O-β-D-glucopyranoside (7), kaempferide-3-O-α-L-rhamnopyranosyl (1→6)-β-D-glucopyranoside (8) and kaempferol-3-O-α-L-rhamno-pyranosyl (1→6)-β-D-glucopyranoside (9), all reported for the first time from this species. The structures of these compounds were deduced on the basis of spectroscopic studies, including 1D and 2D NMR techniques. Compounds 1-9 were investigated for biological activity and showed significant anti-inflammatory activity in the carrageen induced rat paw edema test. The antioxidant activities of isolated compounds 1-9 were evaluated by the DPPH radical scavenging test, and compounds 1, 2, 4 and 7-9 exhibited marked scavenging activity compared to the standard BHA. These compounds were further studied for their anti-glycation properties and some compounds showed significant anti-glycation inhibitory activity. The purity of compounds 2-5, 8 and 9 was confirmed by HPLC. The implications of these results for the chemotaxonomic studies of the genus Cordia have also been discussed.

Advanced glycation end products in the skin are enhanced in COPD

NARCIS (Netherlands)

Hoonhorst, Susan J. M.; Loi, Adele T. Lo Tam; Hartman, Jorine E.; Telenga, Eef D.; van den Berge, Maarten; Koenderman, Leo; Lammers, Jan Willem J.; Boezen, H. Marike; Postma, Dirkje S.; ten Hacken, Nick H. T.

Background. Cigarette smoking is the main cause of chronic obstructive pulmonary disease (COPD) inducing oxidative stress and local tissue injury, resulting in pulmonary inflammation. Advanced glycation end products (AGEs) are produced by glycation and oxidation processes and their formation is

Hemoglobin Wayne Trait with Incidental Polycythemia.

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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. © 2017 by the Association of Clinical Scientists, Inc.

The Hemoglobin E Thalassemias

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Fucharoen, Suthat; Weatherall, David J.

2012-01-01

Hemoglobin E (HbE) is an extremely common structural hemoglobin variant that occurs at high frequencies throughout many Asian countries. It is a β-hemoglobin variant, which is produced at a slightly reduced rate and hence has the phenotype of a mild form of β thalassemia. Its interactions with different forms of α thalassemia result in a wide variety of clinical disorders, whereas its coinheritance with β thalassemia, a condition called hemoglobin E β thalassemia, is by far the most common severe form of β thalassemia in Asia and, globally, comprises approximately 50% of the clinically severe β-thalassemia disorders. PMID:22908199

Characterisation of advanced glycation endproducts in saliva from patients with diabetes mellitus

International Nuclear Information System (INIS)

Yoon, Min-Sung; Jankowski, Vera; Montag, Susanne; Zidek, Walter; Henning, Lars; Schlueter, Hartmut; Tepel, Martin; Jankowski, Joachim

2004-01-01

Patients with diabetes mellitus are prone to develop increased advanced glycation endproducts causing local complications and increased overall morbidity and mortality. Nuclear magnetic resonance spectra were determined in saliva of 52 consecutive patients with diabetes mellitus and 47 age-matched healthy control subjects. Resonance spectra showed specific peaks at 2.3, 7.3, and 8.4 ppm in saliva from patients with diabetes mellitus. These peaks could be generated by incubation of saliva from healthy control subjects with hypochloric acid in vitro, indicating the presence of advanced glycation endproducts. The presence of advanced glycation endproducts in patients with diabetes mellitus was associated with approximal plaque index, indicating increased periodontal damage. The study indicates that increased advanced glycation endproducts are involved in the pathogenesis of diabetic complications

Comparable Dietary Patterns Describe Dietary Behavior across Ethnic Groups in the Netherlands, but Different Elements in the Diet Are Associated with Glycated Hemoglobin and Fasting Glucose Concentrations.

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Dekker, Louise H; van Dam, Rob M; Snijder, Marieke B; Peters, Ron J G; Dekker, Jacqueline M; de Vries, Jeanne H M; de Boer, Evelien J; Schulze, Matthias B; Stronks, Karien; Nicolaou, Mary

2015-08-01

Ethnic minority populations in Western societies suffer from a disproportionate burden of type 2 diabetes (T2D). Insight into the role of dietary patterns in T2D may assist public health nutrition efforts in addressing these health disparities. We explored the association between dietary patterns and biomarkers of T2D in 5 ethnic groups living in Amsterdam, Netherlands. A total of 3776 men and women aged 18-70 y of Dutch, South Asian Surinamese, African-Surinamese, Turkish, and Moroccan origin from the HELIUS (HEalthy LIfe in an Urban Setting) study were included. Diet was assessed by using a food-frequency questionnaire, and dietary patterns were derived separately per ethnic group. First, food group-based dietary patterns were derived by using principal components analysis and the association with glycated hemoglobin (HbA1c) and plasma fasting glucose was assessed by using multivariable linear regression. Second, biomarker-driven dietary patterns based on HbA1c and fasting glucose concentrations were derived by applying reduced rank regression. Two comparable food group-based dietary patterns were identified in each ethnic group: a "meat and snack" pattern and a "vegetable" pattern. The meat-and-snack pattern derived within the Dutch origin population was significantly associated with HbA1c (β = 0.09; 95% CI: 0.00, 0.19) and fasting glucose (β = 0.18; 95% CI: 0.09, 0.26) concentrations. A biomarker-derived pattern characterized by red and processed meat was observed among Dutch-origin participants; however, among ethnic minority groups, this pattern was characterized by other foods including ethnicity-specific foods (e.g., roti, couscous). Although similar food group dietary patterns were derived within 5 ethnic groups, the association of the meat-and-snack pattern with fasting glucose concentrations differed by ethnicity. Taken together with the finding of ethnic differences in biomarker-driven dietary patterns, our results imply that addressing T2D risk in

Blood Pressure Is the Determinant for the Increased Risk for Intracranial Arterial Stenosis in Subjects with Elevated Glycated Hemoglobin Levels: The Kangbuk Samsung Health Study.

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Oh, Hyung-Geun; Rhee, Eun-Jung

2016-11-01

Ischemic stroke is known to be an important vascular complication of diabetes. Intracranial arterial stenosis (ICAS) is considered as an important cause of stroke in Asians. We aimed to analyze the risk for ICAS assessed by transcranial Doppler (TCD) ultrasonography in different groups of young Korean subjects divided by glycated hemoglobin (HbA1c) levels. This study included 10,437 participants without history of cardiovascular diseases (81.3% men, mean age 43 years) from a health screening program, in whom TCD ultrasonography was used to detect greater than 50% ICAS based on criteria modified from the SONIA (Stroke Outcomes and Neuroimaging of Intracranial Atherosclerosis) trial. The subjects were divided into 3 groups according to HbA1c levels: HbA1c < 5.7%, 5.7 ≤ HbA1c < 6.5%, and HbA1c ≥ 6.5% or under medication for diabetes. Among the participants, 3.0% of the subjects had ICAS. The subjects with ICAS tended to have higher mean HbA1c level compared with those without ICAS (5.8 ± .8 versus 5.7 ± .6, P = .063). The proportion of subjects with ICAS significantly increased as the HbA1c increased from the first to the third group (2.8%, 3.0%, 4.6%, P for linear trend = .022). In logistic regression analysis with ICAS as the dependent variable, the group with HbA1c ≥ 6.5% showed significantly increased odds ratio for ICAS with subjects with HbA1c < 5.7% as the reference after adjustment for confounding variables (1.575, 95% confidence interval 1.056-2.347). However, this significance disappeared with inclusion of presence of hypertension in the model. The risk for ICAS assessed by TCD was increased in young Korean subjects with HbA1c ≥ 6.5%. However, this significance was attenuated after adjustment for presence of hypertension, suggesting the importance of hypertension in ICAS. Copyright © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Determination of Mean Glycated Haemoglobin in Healthy Adults of a Local Population.

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Nida, Sumbal; Khan, Dilshad Ahmed; Ijaz, Aamir; Khan, Muhammad Qaiser Alam; Aleef, Hira; Abbasi, Maria

2017-07-01

To determine the mean hemoglobin HbA1C levels of disease-free adults in a local population and its optimum cutoff for the diagnosis of diabetes. Cross-sectional study. Department of Chemical Pathology and Endocrinology, Armed Forces Institute of Pathology, Rawalpindi, from January to September 2015. Healthy subjects aged 18 years and above of either gender were recruited from local population. Pregnant ladies and individuals with known diabetes, chronic kidney disease, chronic liver disease, congestive cardiac failure, anemia, hemoglobinopathies, mental illness and individuals on glucocorticoid therapy were excluded. Fasting plasma glucose (FPG) or 2-hour plasma glucose (2-h PG) was analyzed using hexokinase methodology and glycated hemoglobin (Hb A1C) was also analyzed using turbidimetric inhibition immunoassay technique. Receiver operating characteristic (ROC) curves were plotted. Differences among the groups were tested by one-way ANOVA, and p <0.05 was considered statistically significant. Among 558 subjects, 88.8% (496) were normoglycaemic (NG), 5.7% (32) were with impaired glucose fasting (IFG), and 5.4% (30) were diagnosed with diabetes mellitus (DM). A1C was 5.00 ±0.44% in NG and 6.28 ±1.16% in diabetics. FPG in NG was 4.55 ±0.95 mmol/Land in diabetics was 8.28 ±1.78 mmol/L. The optimal HbA1C cutoff value for diagnosis of DM was at 6.05% (AUC 0.827 95% CI 0.732 to 0.923, p ≤0.05 with its sensitivity of 53.3% and specificity of 98.5%. However, HbA1C showed suboptimal sensitivity and specificity for prediabetes. The mean HbAIC and cutoff point for diabetes in the study population is 5.07 ±0.58% and 6.05%, respectively (AUC 0.827, 95% CI: 0.732 to 0.923, p<0.001) with 53.3% sensitivity and 98.5% specificity.

The effect of Cerasus avium stalk extract on albumin glycation reaction

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Mohadeseh Abdoli

2014-10-01

Full Text Available Background: Non-enzymatic glycosylation of proteins is the major cause of diabetic complications. The inhibition of glycation process can reduce complications of diabetes. In the Iranian traditional medicine, the decoction (boiled extraction of Cerasus avium stalk is used as a hypoglycemic agent. The aim of this study was to investigate the in vitro inhibitory effects of decoction and ethanolic and aqueous extracts of Cerasus avium stalk on albumin glycation reaction. Methods: In this experimental study, first, the ethanolic, aqueous and decoction extracts of Cerasus avium stalk were prepared. Then, different concentrations of these extracts were prepared and added to albumin and glucose solutions. Finally, compared to control group that was not treated with any extracts, the albumin glycation rate in the groups treated with various concentrations of extracts was evaluated using TBA (thio-barbituric acid method. Results: The results showed that compared to control group, decoction of Cerasus avium stalk in the concentrations of 20, 10 and 2 mg/dl could reduce albumin glycation to 85.10±1.55, 72.35±1.75 and 51.25±1.22 %, respectively (P>0.001. Moreover, in the concentration of 20 mg/dl, the inhibitory effect of decoction of Cerasus avium stalk on the albumin glycation reaction was higher than those of aqueous (P=0.021 and ethanolic (P=0.009 extracts. Conclusion: The findings showed that the extracs of Cerasus avium stalk, in particular in the decoction form, could significantly reduce the rate of albumin glycation; therefore, it can be used for decreasing diabetes mellitus complications.

"STUDY ON THE EFFECT OF GARLIC ON THE IN VITRO ALBUMIN GLYCATION REACTION"

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N. Sheikh

2004-05-01

Full Text Available Garlic, an antioxidant plant, can react with amino groups of proteins to form Schiff bases. As diabetes leads to glycation of various proteins and this in turn has some effects on the structure of proteins and biochemical activity of them, the inhibition of this process seems very vital. For several years researchers in this field have done their best to recognize the antidiabetic compounds. The aim of this study is to determine the effects of garlic on albumin glycation in vitro.In the presence of various concentrations of garlic, albumin was glycated and evaluated using TBA (thio-barbituric acid method. The results showed that garlic has a statistically significant (P<0.05 effect in inhibiting or decreasing the reaction of albumin glycation. The findings of this research shows that garlic probably inhibits the reaction of glycation and decreases complications occurring in diabetes.

Phylogeny of Echinoderm Hemoglobins.

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Ana B Christensen

Full Text Available 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.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.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 vertebrates.

Impaired CD4+ and T-helper 17 cell memory response to Streptococcus pneumoniae is associated with elevated glucose and percent glycated hemoglobin A1c in Mexican Americans with type 2 diabetes mellitus.

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Martinez, Perla J; Mathews, Christine; Actor, Jeffrey K; Hwang, Shen-An; Brown, Eric L; De Santiago, Heather K; Fisher Hoch, Susan P; McCormick, Joseph B; Mirza, Shaper

2014-01-01

Individuals with type 2 diabetes are significantly more susceptible to pneumococcal infections than healthy individuals of the same age. Increased susceptibility is the result of impairments in both innate and adaptive immune systems. Given the central role of T-helper 17 (Th17) and T-regulatory (Treg) cells in pneumococcal infection and their altered phenotype in diabetes, this study was designed to analyze the Th17 and Treg cell responses to a whole heat-killed capsular type 2 strain of Streptococcus pneumoniae. Patients with diabetes demonstrated a lower frequency of total CD+T-cells, which showed a significant inverse association with elevated fasting blood glucose. Measurement of specific subsets indicated that those with diabetes had, low intracellular levels of interleukin (IL)-17, and lower pathogen-specific memory CD4+ and IL-17+ cell numbers. No significant difference was observed in the frequency of CD4+ and Th17 cells between those with and without diabetes. However, stratification of data by obesity indicated a significant increase in frequency of CD4+ and Th17 cells in obese individuals with diabetes compared with nonobese individual with diabetes. The memory CD+T-cell response was associated inversely with both fasting blood glucose and percent glycated hemoglobin A1c. This study demonstrated that those with type 2 diabetes have a diminished pathogen-specific memory CD4+ and Th17 response, and low percentages of CD+T-cells in response to S. pneumoniae stimulation. Copyright © 2014 Mosby, Inc. All rights reserved.

Human Achilles tendon glycation and function in diabetes

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Couppe, Christian; Svensson, Rene Brüggebusch; Kongsgaard, Mads

2016-01-01

Diabetic patients have an increased risk of foot ulcers, and glycation of collagen may increase tissue stiffness. We hypothesized that the level of glycemic control (glycation) may affect Achilles tendon stiffness, which can influence gait pattern. We therefore investigated the relationship between...... tissue cross-linking were greater in diabetic patients compared to controls. The higher foot pressure indicates that material stiffness of tendon and other tissue (e.g skin and joint capsule) may influence on foot gait. The difference in foot pressure distribution may contribute to the development...... of foot ulcers in diabetic patients....

Effect of glycation of albumin on its renal clearance in normal and diabetic rats

International Nuclear Information System (INIS)

Layton, G.J.; Jerums, G.

1988-01-01

Two independent techniques have been used to study the renal clearances of nonenzymatically glycated albumin and nonglycated albumin in normal and streptozotocin-induced diabetic rats, 16 to 24 weeks after the onset of diabetes. In the first technique, serum and urinary endogenous glycated and nonglycated albumin were separated using m-aminophenylboronate affinity chromatography and subsequently quantified by radioimmunoassay. Endogenous glycated albumin was cleared approximately twofold faster than nonglycated albumin in normal and diabetic rats. However, no difference was observed in the glycated albumin/nonglycated albumin clearance ratios (Cga/Calb) in normal and diabetic rats, respectively (2.18 +/- 0.39 vs 1.83 +/- 0.22, P greater than 0.05). The second technique measured the renal clearance of injected 125I-labelled glycated albumin and 125I-labelled albumin. The endogenous results were supported by the finding that 125I-labelled glycated albumin was cleared more rapidly than 125I-labelled albumin in normal (P less than 0.01) and diabetic (P less than 0.05) rats. The Cga/Calb ratio calculated for the radiolabelled albumins was 1.4 and 2.0 in normal and diabetic rats, respectively. This evidence suggests that nonenzymatic glycation of albumin increases its renal clearance to a similar degree in normal and diabetic rats

Prognostic Factors Affecting Locally Recurrent Rectal Cancer and Clinical Significance of Hemoglobin

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Rades, Dirk; Kuhn, Hildegard; Schultze, Juergen; Homann, Nils; Brandenburg, Bernd; Schulte, Rainer; Krull, Andreas; Schild, Steven E.; Dunst, Juergen

2008-01-01

Purpose: To investigate potential prognostic factors, including hemoglobin levels before and during radiotherapy, for associations with survival and local control in patients with unirradiated locally recurrent rectal cancer. Patients and Methods: Ten potential prognostic factors were investigated in 94 patients receiving radiotherapy for recurrent rectal cancer: age (≤68 vs. ≥69 years), gender, Eastern Cooperative Oncology Group performance status (0-1 vs. 2-3), American Joint Committee on Cancer (AJCC) stage (≤II vs. III vs. IV), grading (G1-2 vs. G3), surgery, administration of chemotherapy, radiation dose (equivalent dose in 2-Gy fractions: ≤50 vs. >50 Gy), and hemoglobin levels before (<12 vs. ≥12 g/dL) and during (majority of levels: <12 vs. ≥12 g/dL) radiotherapy. Multivariate analyses were performed, including hemoglobin levels, either before or during radiotherapy (not both) because these are confounding variables. Results: Improved survival was associated with better performance status (p < 0.001), lower AJCC stage (p = 0.023), surgery (p = 0.011), chemotherapy (p = 0.003), and hemoglobin levels ≥12 g/dL both before (p = 0.031) and during (p < 0.001) radiotherapy. On multivariate analyses, performance status, AJCC stage, and hemoglobin levels during radiotherapy maintained significance. Improved local control was associated with better performance status (p = 0.040), lower AJCC stage (p = 0.010), lower grading (p = 0.012), surgery (p < 0.001), chemotherapy (p < 0.001), and hemoglobin levels ≥12 g/dL before (p < 0.001) and during (p < 0.001) radiotherapy. On multivariate analyses, chemotherapy, grading, and hemoglobin levels before and during radiotherapy remained significant. Subgroup analyses of the patients having surgery demonstrated the extent of resection to be significantly associated with local control (p = 0.011) but not with survival (p = 0.45). Conclusion: Predictors for outcome in patients who received radiotherapy for locally

Fish hemoglobins

OpenAIRE

Souza,P.C. de; Bonilla-Rodriguez,G.O.

2007-01-01

Vertebrate hemoglobin, contained in erythrocytes, is a globular protein with a quaternary structure composed of 4 globin chains (2 alpha and 2 beta) and a prosthetic group named heme bound to each one. Having myoglobin as an ancestor, hemoglobin acquired the capacity to respond to chemical stimuli that modulate its function according to tissue requirements for oxygen. Fish are generally submitted to spatial and temporal O2 variations and have developed anatomical, physiological and biochemica...

The Extract of Litsea japonica Reduced the Development of Diabetic Nephropathy via the Inhibition of Advanced Glycation End Products Accumulation in db/db Mice

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Eunjin Sohn

2013-01-01

Full Text Available Increasing evidence indicates that advanced glycation end products (AGEs contribute to the pathogenesis of diabetic nephropathy. The aim of this study was to investigate the protective effect of L. japonica extract (LJE against renal damage in the db/db mouse. LJE (100 or 250 mg/kg per day was given to diabetic mice for 12 weeks. Body weight, blood glucose levels, glycated hemoglobin (HbA1c levels, and proteinuria were examined. In in vitro assay of the inhibition of AGE formation, immunohistochemical analysis of podocyte loss and AGE accumulations were performed. In 20-week-old db/db mice, severe hyperglycemia developed, and proteinuria was significantly increased. Diabetes induced markedly morphological alterations to the renal glomerular cells. AGE accumulations and podocyte loss were detected in renal glomeruli. LJE treatment significantly reduced proteinuria and AGE accumulations in diabetic mice. Moreover, the loss of nephrin, an important slit diaphragm component in the kidneys, was restored by LJE treatment. Our studies suggest that LJE might be beneficial for the treatment of diabetic nephropathy. The ability of LJE to attenuate proteinuria and podocyte dysfunction may be mediated by the inhibition of AGE accumulation in the context of diabetic nephropathy in db/db mice.

Acute insulin resistance mediated by advanced glycation endproducts in severely burned rats.

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Zhang, Xing; Xu, Jie; Cai, Xiaoqing; Ji, Lele; Li, Jia; Cao, Bing; Li, Jun; Hu, Dahai; Li, Yan; Wang, Haichang; Xiong, Lize; Xiao, Ruiping; Gao, Feng

2014-06-01

Hyperglycemia often occurs in severe burns; however, the underlying mechanisms and importance of managing postburn hyperglycemia are not well recognized. This study was designed to investigate the dynamic changes of postburn hyperglycemia and the underlying mechanisms and to evaluate whether early glycemic control is beneficial in severe burns. Prospective, randomized experimental study. Animal research laboratory. Sprague-Dawley rats. Anesthetized rats were subjected to a full-thickness burn injury comprising 40% of the total body surface area and were randomized to receive vehicle, insulin, and a soluble form of receptor for advanced glycation endproducts treatments. An in vitro study was performed on cultured H9C2 cells subjected to vehicle or carboxymethyllysine treatment. We found that blood glucose change presented a distinct pattern with two occurrences of hyperglycemia at 0.5- and 3-hour postburn, respectively. Acute insulin resistance evidenced by impaired insulin signaling and glucose uptake occurred at 3-hour postburn, which was associated with the second hyperglycemia and positively correlated with mortality. Mechanistically, we found that serum carboxymethyllysine, a dominant species of advanced glycation endproducts, increased within 1-hour postburn, preceding the occurrence of insulin resistance. More importantly, treatment of animals with soluble form of receptor for advanced glycation endproducts, blockade of advanced glycation endproducts signaling, alleviated severe burn-induced insulin resistance. In addition, early hyperglycemic control with insulin not only reduced serum carboxymethyllysine but also blunted postburn insulin resistance and reduced mortality. These findings suggest that severe burn-induced insulin resistance is partly at least mediated by serum advanced glycation endproducts and positively correlated with mortality. Early glycemic control with insulin or inhibition of advanced glycation endproducts with soluble form of receptor

Hemoglobin C, S-C, and E Diseases

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... quickly than others, resulting in chronic anemia. Hemoglobin C disease Hemoglobin C disease occurs mostly in blacks. ... a common complication of hemoglobin C disease. Hemoglobin S-C disease Hemoglobin S-C disease occurs in people who ...

The Effect of Turmeric , Cardamom and Ginger on in vitro Albumin Glycation

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N. Sheikh

2004-01-01

Full Text Available Diabetes mellitus is one of the most common disease in the world that imposes a tremendous health and societal burden whether that burden is measured in terms of sickness , use of health systems resources or costs. Hyperglycemia is the most important clinical sign of diabetes leading to glycation of the various proteins in the body that leads to change in their nature , structure and biochemical activity. One of the probable methods in the treatment of diabetes mellitus is decrease or inhibition of this reaction. It seems that Turmeric , Cardamom and Ginger are useful for this purpose. The main goal of this research is to determine the effect of above agents on in vitro albumin glycation. In the presence of various concentration of these agents , albumin was glycated and evaluated using TBA method. Results showed that these food additives have inhibitory effects on albumin glycation reaction with the concentraction of 1 g/dl , 0.2 g/dl and 0.1 g/dl. Among these agents , Ginger had the most inhibitory effect (78% with the concentration of 1 g/dl. The sequence of effect is : Ginger > Cardamom > Turmeric These findings showed that these agents decrease albumin glycation reaction.

Glycation of extracellular matrix proteins and its role in atherosclerosis 

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Aleksandra Kuzan

2012-10-01

Full Text Available Glycation consists in formation of advanced glycation end-products (AGE during non-enzymatic reaction between reducing sugars and proteins, lipids or nucleic acids. This review is focused mainly on glycation of collagen and its role in acceleration of vascular disease. Collagen is an extracellular matrix protein characterized by unique structure forming fibrils with great anti-tensile and anti-breaking strength. The protein builds the connective tissue and is responsible for biomechanical properties of blood vessels. It is reported that higher content of glycated collagen correlates with lower elasticity and greater toughness of the vessel walls and, as a consequence, a faster rate of atherosclerosis development. Numerous mechanisms connected with AGE formation are involved in atherogenesis, among others: receptor-mediated production of free radicals, triggering an inflammatory process, activation of leukocytes and thrombocytes, facilitation of LDL binding, change in level of growth factors, adhesion molecules, MMP and some other proteins’ expression. The coverages allow the development of therapeutic strategies to prevent or slow down the pathological processes connected with glycation of collagen and other proteins in the artery wall. The main strategies are based on limitation of exogenous AGE, consumption of products which contain rutin, treatment with drugs which inhibit AGE formation, such aspyridoxamine, and chemicals which are able to cleave already formed AGE protein-protein crosslinks, such as ALT-711.

Prevalence of Prediabetes and Undiagnosed Diabetes in Patients with HFpEF and HFrEF and Associated Clinical Outcomes

DEFF Research Database (Denmark)

Kristensen, Søren L; Jhund, Pardeep S; Lee, Matthew M Y

2017-01-01

PURPOSE: The prevalence and consequences of prediabetic dysglycemia and undiagnosed diabetes is unknown in patients with heart failure (HF) and preserved ejection fraction (HFpEF) and has not been compared to heart failure and reduced ejection fraction (HFrEF). METHODS: We examined the prevalence...... and outcomes associated with normoglycemia, prediabetic dysglycemia and diabetes (diagnosed and undiagnosed) among individuals with a baseline glycated hemoglobin (hemoglobin A1c, HbA1c) measurement stratified by HFrEF or HFpEF in the Candesartan in Heart failure Assessment of Reduction in Mortality...... and was available in 1072/3023 (35%) of patients with HFpEF and 1578/4576 (34%) patients with HFrEF. 18 and 16% had normoglycemia (HbA1c prediabetes (HbA1c 6.0-6.4), respectively. Finally among patients with HFpEF 22% had undiagnosed diabetes (HbA1c > 6.4), and 40% had known diabetes (any Hb...

A novel monoclonal antibody targeting carboxymethyllysine, an advanced glycation end product in atherosclerosis and pancreatic cancer.

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Ulrika Wendel

Full Text Available Advanced glycation end products are formed by non-enzymatic reactions between proteins and carbohydrates, causing irreversible lysine and arginine alterations that severely affect protein structure and function. The resulting modifications induce inflammation by binding to scavenger receptors. An increase in advanced glycation end products is observed in a number of diseases e.g. atherosclerosis and cancer. Since advanced glycation end products also are present in healthy individuals, their detection and quantification are of great importance for usage as potential biomarkers. Current methods for advanced glycation end product detection are though limited and solely measure total glycation. This study describes a new epitope-mapped single chain variable fragment, D1-B2, against carboxymethyllysine, produced from a phage library that was constructed from mouse immunizations. The phage library was selected against advanced glycation end product targets using a phage display platform. Characterization of its binding pattern was performed using large synthetic glycated peptide and protein libraries displayed on microarray slides. D1-B2 showed a preference for an aspartic acid, three positions N-terminally from a carboxymethyllysine residue and also bound to a broad collection of glycated proteins. Positive immunohistochemical staining of mouse atherosclerotic plaques and of a tissue microarray of human pancreatic tumors confirmed the usability of the new scFv for advanced glycation end product detection in tissues. This study demonstrates a promising methodology for high-throughput generation of epitope-mapped monoclonal antibodies against AGE.

Antioxidant, Anti-Glycation and Anti-Inflammatory Activities of Phenolic Constituents from Cordia sinensis

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Muhammad Nasir

2011-12-01

Full Text Available Nine compounds have been isolated from the ethyl acetate soluble fraction of C. sinensis, namely protocatechuic acid (1, trans-caffeic acid (2, methyl rosmarinate (3, rosmarinic acid (4, kaempferide-3-O-β-D-glucopyranoside (5, kaempferol-3-O-β-D-glucopyranoside (6, quercetin-3-O-β-D-glucopyranoside (7, kaempferide-3-O-α-L-rhamnopyranosyl (1→6-β-D-glucopyranoside (8 and kaempferol-3-O-α-L-rhamno-pyranosyl (1→6-β-D-glucopyranoside (9, all reported for the first time from this species. The structures of these compounds were deduced on the basis of spectroscopic studies, including 1D and 2D NMR techniques. Compounds 1–9 were investigated for biological activity and showed significant anti-inflammatory activity in the carrageen induced rat paw edema test. The antioxidant activities of isolated compounds 1–9 were evaluated by the DPPH radical scavenging test, and compounds 1, 2, 4 and 7–9 exhibited marked scavenging activity compared to the standard BHA. These compounds were further studied for their anti-glycation properties and some compounds showed significant anti-glycation inhibitory activity. The purity of compounds 2–5, 8 and 9 was confirmed by HPLC. The implications of these results for the chemotaxonomic studies of the genus Cordia have also been discussed.

Neurite regeneration in adult rat retinas exposed to advanced glycation end-products and regenerative effects of neurotrophin-4.

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Bikbova, Guzel; Oshitari, Toshiyuki; Yamamoto, Shuichi

2013-10-09

The purpose of this study was to determine the effect of low concentrations of advanced glycation end-products on neurite regeneration in isolated rat retinas, and to determine the effects of neurotrophin-4 on regeneration in advanced glycation end-products exposed retinas. Retinal explants of 4 adult Sprague-Dawley rats were cultured on collagen gel and were incubated in; (1) serum-free control culture media, (2) glucose-advanced glycation end-products-bovine serum albumin media, (3) glycolaldehyde-advanced glycation end-products-bovine serum albumin media, (4) glyceraldehyde-advanced glycation end-products-bovine serum albumin media, (5) glucose-advanced glycation end-products+neurotrophin-4 media, (6) glycolaldehyde-advanced glycation end-products+neurotrophin-4 media, or (7) glyceraldehyde-advanced glycation end-products+neurotrophin-4 supplemented culture media. After 7 days, the number of regenerating neurites from the explants was counted. Then, explants were fixed, cryosectioned, and stained for TUNEL. The ratio of TUNEL-positive cells to all cells in the ganglion cell layer was determined. Immunohistochemical examinations for the active-form of caspase-9 and apoptosis-inducing factor were performed. In retinas incubated with advanced glycation end-products containing media, the number of regenerating neurites were fewer than in retinas without advanced glycation end-products, and the number of TUNEL-positive cells and caspase-9- and apoptosis-inducing factor-immunopositive cells was significantly higher than in control media. Neurotrophin-4 supplementation increased the numbers of regenerating neuritis, and the number of TUNEL-positives, caspase-9-, and apoptosis-inducing factor-immunopositive cells were significantly fewer than that in advanced glycation end-products without neurotrophin-4 media. Low doses of advanced glycation end-products impede neurite regeneration in the rat retinas. Neurotrophin-4 significantly enhances neurite regeneration in

Evaluation of the Antioxidant and Anti-glication Effects of the Hexane Extract from Piper auritum Leaves in Vitro and Beneficial Activity on Oxidative Stress and Advanced Glycation End-Product-Mediated Renal Injury in Streptozotocin-Treated Diabetic Rats

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Adriana Maria Neira Gonzalez

2012-10-01

Full Text Available The aim of this study was to investigate the antioxidant activity of hexane extracts from leaves of Piper auritum (HS. Eight complementary in vitro test methods were used, including inhibition of DPPH· radicals, nitric oxide, superoxide anion, ion-chelating, ABTS, oxygen radical absorbance capacity, β-carotene bleaching and peroxy radical scavenging. The results indicated that HS possesses high antioxidant activity. To add to these finding we tested the effect against oxidative stress in liver, pancreas and kidney in diabetic rats. Low levels of SOD, CAT, GPx and GSH in diabetic rats were reverted to near normal values after treatment with HS. These results suggest that P. auritum prevents oxidative stress, acting as a suppressor of liver cell damage. Given the link between glycation and oxidation, we proposed that HS might possess significant in vitro antiglycation activity. Our data confirmed the inhibitory effect of HS on bovine serum albumin, serum glycosylated protein, glycation of LDL, and glycation hemoglobin. The effect of HS on diabetic renal damage was investigated using streptozotocin-induced diabetic rats. The oral administration of HS at a dose of 200 and 400 mg/kg body weight/day for 28 days significantly reduced advanced glycation endproduct (AGE formation, elevated renal glucose and thiobarbituric acid-reactive substance levels in the kidneys of diabetic rats. This implies that HS would alleviate the oxidative stress under diabetes through the inhibition of lipid peroxidation. These findings indicate that oxidative stress is increased in the diabetic rat kidney and that HS can prevent renal damage associated with diabetes by attenuating the oxidative stress.

Anti-glycated and antiradical activities in vitro of polysaccharides from Ganoderma capense.

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Yan, Chunyan; Kong, Fansheng; Zhang, Dezhi; Cui, Jiangxia

2013-01-01

Ganoderma capense is a Ganoderma species and is widely used, especially in Asia, as a well-known medicinal mushroom for health-promoting effect and for treatment of chronic diseases, such as diabetes, aging, etc. G. capense is rich of polysaccharide. To isolate the polysaccharides from G. capense and evaluate their anti-glycated and antiradical activities in vitro. The dried powder of submerged fermentation culturing mycelium of G. capense was defatted, extracted with water/alkaline water followed by ethanol precipitation and deproteinated. And four crude polysaccharides, named as GC50, GC70, GC90 and GCB, were obtained. For the first time, the in vitro anti-glycated activities of the four samples were studied by non-enzymatic glycation reaction. Then, the DPPH radical and hydroxyl radical assays were established to estimate the antiradical capacity of the four samples. Meanwhile the contents of polysaccharides were determined by phenol-sulphuric acid colorimetry. Preliminary antiradical in vitro studies indicated that the four crude polysaccharides showed concentration-dependent scavenging abilities on DPPH and hydroxyl radicals. The evaluation of anti-glycation activity suggested that GC70 had good potential for inhibiting the formation of advanced glycation end products. Time- and dose-dependent effects were also observed for all GC70 samples.

Cross-linking in collagen by nonenzymatic glycation increases the matrix stiffness in rabbit achilles tendon.

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Reddy, G Kesava

2004-01-01

Nonenzymatic glycation of connective tissue matrix proteins is a major contributor to the pathology of diabetes and aging. Previously the author and colleagues have shown that nonenzymatic glycation significantly enhances the matrix stability in the Achilles tendon (Reddy et al., 2002, Arch. Biochem. Biophys., 399, 174-180). The present study was designed to gain further insight into glycation-induced collagen cross-linking and its relationship to matrix stiffness in the rabbit Achilles tendon. The glycation process was initiated by incubating the Achilles tendons (n = 6) in phosphate-buffered saline containing ribose, whereas control tendons (n = 6) were incubated in phosphate-buffered saline without ribose. Eight weeks following glycation, the biomechanical attributes as well as the degree of collagen cross-linking were determined to examine the potential associations between matrix stiffness and molecular properties of collagen. Compared to nonglycated tendons, the glycated tendons showed increased maximum load, stress, strain, Young's modulus of elasticity, and toughness indicating that glycation increases the matrix stiffness in the tendons. Glycation of tendons resulted in a considerable decrease in soluble collagen content and a significant increase in insoluble collagen and pentosidine. Analysis of potential associations between the matrix stiffness and degree of collagen cross-linking showed that both insoluble collagen and pentosidine exhibited a significant positive correlation with the maximum load, stress, and strain, Young's modulus of elasticity, and toughness (r values ranging from.61 to.94) in the Achilles tendons. However, the soluble collagen content present in neutral salt buffer, acetate buffer, and acetate buffer containing pepsin showed an inverse relation with the various biomechanical attributes tested (r values ranging from.22 to.84) in the Achilles tendons. The results of the study demonstrate that glycation-induced collagen cross

Exploring the antioxidant property of bioflavonoid quercetin in preventing DNA glycation: A calorimetric and spectroscopic study

International Nuclear Information System (INIS)

Sengupta, Bidisa; Uematsu, Takashi; Jacobsson, Per; Swenson, Jan

2006-01-01

Reducing sugars for example glucose, fructose, etc., and their phosphate derivatives non-enzymatically glycate biological macromolecules (e.g., proteins, DNA and lipids) and is related to the production of free radicals. Here we present a novel study, using differential scanning calorimetry (DSC) along with UV/Vis absorption and photon correlation spectroscopy (PCS), on normal and glycated human placenta DNA and have explored the antioxidant property of the naturally occurring polyhydroxy flavone quercetin (3,3',4',5,7-pentahydroxyflavone) in preventing the glycation. The decrease in the absorption intensity of DNA in presence of sugars clearly indicates the existence of sugar molecules between the two bases of a base pair in the duplex DNA molecule. Variations were perceptible in the PCS relaxation profiles of normal and glycated DNA. The melting temperature of placenta DNA was decreased when glycated suggesting a decrease in the structural stability of the double-stranded glycated DNA. Our DSC and PCS data showed, for the first time, that the dramatic changes in the structural properties of glycated DNA can be prevented to a significant extent by adding quercetin. This study provides valuable insights regarding the structure, function, and dynamics of normal and glycated DNA molecules, underlying the manifestation of free radical mediated diseases, and their prevention using therapeutically active naturally occurring flavonoid quercetin

Hemoglobin Test: MedlinePlus Lab Test Information

Science.gov (United States)

... page: https://medlineplus.gov/labtests/hemoglobintest.html Hemoglobin Test To use the sharing features on this page, please enable JavaScript. What is a Hemoglobin Test? A hemoglobin test measures the levels of hemoglobin ...

Monotopic modifications derived from in vitro glycation of albumin with ribose

Czech Academy of Sciences Publication Activity Database

Pataridis, Statis; Šťastná, Zdeňka; Sedláková, Pavla; Mikšík, Ivan

2013-01-01

Roč. 34, č. 12 (2013), s. 1757-1763 ISSN 0173-0835 R&D Projects: GA ČR(CZ) GAP206/12/0453; GA ČR(CZ) GA203/08/1428 Institutional support: RVO:67985823 Keywords : advanced glycation end product (AGE) * albumin * CE-MS * glycation * LC-MS/MS Subject RIV: CB - Analytical Chemistry, Separation Impact factor: 3.161, year: 2013

Monitoring the progress of non-enzymatic glycation in vitro

International Nuclear Information System (INIS)

Shaw, S.M.; Crabbe, M.J.

1994-01-01

The progress of in vitro non-enzymatic glycation of bovine serum albumin was followed by using 14 C-glucose and a nitroblue tetrazolium assay, absorption and fluorescence spectroscopy, SDS gel electrophoresis and protease digestion. The number of adducts detectable using both 14 C-tracers and a fructosamine assay remained low at physiological glucose concentrations, fewer than five adducts being detectable. When glucose concentrations > 1.0 M were used the number of adducts was found to greatly exceed the number of lysyl residues available in BSA, indicative of cross-linking between Maillard products. Incubation of BSA with glucose concentrations of up to 160 mM for one month produced no observable increase in molecular weight by SDS gel electrophoresis, showing that at physiological glucose concentrations, increases in molecular weight were minimal for short incubation periods. Increases in absorption were proportial to both the glucose concentration and the incubation time. Several absorption peaks, at 370, 488 and 554 nm, were consistent in appearance throughout the course of each incubation. Fluorescence spectroscopy of the modified proteins showed a disappearance of the fluorescence associated with peptide bonds and aromatic residues and the appearance of a broad peak at longer wavelengths due to the wide range of absorptive/fluorescent wavelengths of the developing Maillard products. Protease digestion gave similar patterns with non-glycated and glycated protein, suggesting that glycation did not block digestion sites, and that partial digestion did not cause significant further exposure of susceptible sites. Our results show that while glycation ultimately results in protein conformational changes and the formation of large molecular weight species, these occur at a relatively late stage in the maturation of protein Maillard products, after ≥ nine months of incubation with glucose concentration of ≥ 20 mM. Monitoring of AGE maturation in vitro is better

Erythrocyte enrichment in hematopoietic progenitor cell cultures based on magnetic susceptibility of the hemoglobin.

Directory of Open Access Journals (Sweden)

Xiaoxia Jin

Full Text Available 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.

CORRELATION OF NON-ALCOHOLIC FATTY LIVER DISEASE AND FEATURES OF METABOLIC SYNDROME IN MORBIDLY OBESE PATIENTS IN THE PREOPERATIVE ASSESSMENT FOR BARIATRIC SURGERY

Science.gov (United States)

de BARROS, Fernando; SETÚBAL, Sergio; MARTINHO, José Manoel; FERRAZ, Loraine; GAUDÊNCIO, Andressa

2016-01-01

ABSTRACT Background: Obesity is an epidemic and chronic disease that can bring other comorbidities to the patient. Non-alcoholic fatty liver disease is present in up to 90% of these patients and can progress to hepatitis and hepatocarcinoma. The relationship of this liver disease and obesity is already well known; however, it is possible that some parameters of the comorbidities are more related than others in the pathophysiology of the disease. Aim: Was analyzed the relationship between non-alcoholic fatty liver disease (NAFLD) and the comorbidities of metabolic syndrome in morbidly obese patients. Methods: Was involved ultrasonography and laboratory assessment of obese patients before bariatric surgery. NAFLD was assessed using the same sonography parameters for all patients. Based on the results, the patients were divided into groups with and without NAFLD. Comparisons between them involved clinical and laboratory variables such as fasting blood glucose, insulin, HOMA-IR (homeostasis model assessment - insulin resistance), glycated hemoglobin, total cholesterol and fractions, triglycerides, alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transferase, C-reactive protein, albumin and ferritin. Patients who reported alcohol abuse (defined as the consumption of >14 drinks per week) or who had hepatitis were excluded. Results: Eighty-two patients (74 women and 8 men) were studied, of whom 53 (64.6%) had NAFLD and 29 (35.4%) did not. The levels of glycated hemoglobin (p=0.05) and LDL cholesterol (p=0.01) were significantly altered in patients with NAFLD. However, weight, body mass index and excess weight did not differ significantly between the groups (p=0.835, p=0.488 and p=0.727, respectively). Conclusions: Altered LDL cholesterol and glycated hemoglobin levels were related to the presence of NAFLD. PMID:28076482

Relationship between glycated haemoglobin and fasting plasma ...

African Journals Online (AJOL)

Emmanuel Musenge

2016-07-30

Jul 30, 2016 ... Relationship between glycated haemoglobin and fasting plasma glucose ... major stakeholders in the management of diabetes mellitus to consider FPG as an ..... HbA1c among customers of health examination services.

A new hemoglobin gene from soybean: a role for hemoglobin in all plants

DEFF Research Database (Denmark)

Anderson, C R; Jensen, E O; LLewellyn, D J

1996-01-01

We have isolated a new hemoglobin gene from soybean. It is expressed in cotyledons, stems of seedlings, roots, young leaves, and in some cells in the nodules that are associated with the nitrogen-fixing Bradyrhizobium symbiont. This contrasts with the expression of the leghemoglobins, which...... are active only in the infected cells of the nodules. The deduced protein sequence of the new gene shows only 58% similarity to one of the soybean leghemoglobins, but 85-87% similarity to hemoglobins from the nonlegumes Parasponia, Casuarina, and barley. The pattern of expression and the gene sequence...... indicate that this new gene is a nonsymbiotic legume hemoglobin. The finding of this gene in legumes and similar genes in other species strengthens our previous suggestion that genomes of all plants contain hemoglobin genes. The specialized leghemoglobin gene family may have arisen from a preexisting...

Posttranslational nitro-glycative modifications of albumin in Alzheimer's disease: implications in cytotoxicity and amyloid-β peptide aggregation.

Science.gov (United States)

Ramos-Fernández, Eva; Tajes, Marta; Palomer, Ernest; Ill-Raga, Gerard; Bosch-Morató, Mònica; Guivernau, Biuse; Román-Dégano, Irene; Eraso-Pichot, Abel; Alcolea, Daniel; Fortea, Juan; Nuñez, Laura; Paez, Antonio; Alameda, Francesc; Fernández-Busquets, Xavier; Lleó, Alberto; Elosúa, Roberto; Boada, Mercé; Valverde, Miguel A; Muñoz, Francisco J

2014-01-01

Glycation and nitrotyrosination are pathological posttranslational modifications that make proteins prone to losing their physiological properties. Since both modifications are increased in Alzheimer's disease (AD) due to amyloid-β peptide (Aβ) accumulation, we have studied their effect on albumin, the most abundant protein in cerebrospinal fluid and blood. Brain and plasmatic levels of glycated and nitrated albumin were significantly higher in AD patients than in controls. In vitro turbidometry and electron microscopy analyses demonstrated that glycation and nitrotyrosination promote changes in albumin structure and biochemical properties. Glycated albumin was more resistant to proteolysis and less uptake by hepatoma cells occurred. Glycated albumin also reduced the osmolarity expected for a solution containing native albumin. Both glycation and nitrotyrosination turned albumin cytotoxic in a cell type-dependent manner for cerebral and vascular cells. Finally, of particular relevance to AD, these modified albumins were significantly less effective in avoiding Aβ aggregation than native albumin. In summary, nitrotyrosination and especially glycation alter albumin structural and biochemical properties, and these modifications might contribute for the progression of AD.

Multicenter evaluation of an enzymatic method for glycated albumin.

Science.gov (United States)

Paleari, Renata; Bonetti, Graziella; Callà, Cinzia; Carta, Mariarosa; Ceriotti, Ferruccio; Di Gaetano, Nicola; Ferri, Marilisa; Guerra, Elena; Lavalle, Gabriella; Cascio, Claudia Lo; Martino, Francesca Gabriela; Montagnana, Martina; Moretti, Marco; Santini, Gabriele; Scribano, Donata; Testa, Roberto; Vero, Anna; Mosca, Andrea

2017-06-01

The use of glycated albumin (GA) has been proposed as an additional glycemic control marker particularly useful in intermediate-term monitoring and in situation when HbA 1c test is not reliable. We have performed the first multicenter evaluation of the analytical performance of the enzymatic method quantILab Glycated Albumin assay implemented on the most widely used clinical chemistry analyzers (i.e. Abbott Architect C8000, Beckman Coulter AU 480 and 680, Roche Cobas C6000, Siemens ADVIA 2400 and 2400 XPT). The repeatability of the GA measurement (expressed as CV, %) implemented in the participating centers ranged between 0.9% and 1.2%. The within-laboratory CVs ranged between 1.2% and 1.6%. A good alignment between laboratories was found, with correlation coefficients from 0.996 to 0.998. Linearity was confirmed in the range from 7.6 to 84.7%. The new enzymatic method for glycated albumin evaluated by our investigation is suitable for clinical use. Copyright © 2017 Elsevier B.V. All rights reserved.

Non-invasive hemoglobin monitoring.

Science.gov (United States)

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. Copyright © 2015 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.

Evaluation of the site specific protein glycation and antioxidant capacity of rare sugar-protein/peptide conjugates.

Science.gov (United States)

Sun, Yuanxia; Hayakawa, Shigeru; Ogawa, Masahiro; Izumori, Ken

2005-12-28

Protein-sugar conjugates generated in nonenzymatic glycation of alpha-lactalbumin (LA) with rare sugars [D-allose (All) and D-psicose (Psi)] and alimentary sugars as controls [D-glucose (Glc) and D-fructose (Fru)] were qualitatively determined by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). Mass spectra revealed that the extent of glycation at lysine residues on LA with D-aldose molecules was very much higher than that of glycation with d-ketose molecules. To identify the specific site of glycation, the peptide mapping was established from protease V8 digestion, using a combination of computational cutting of proteins and MALDI-TOF-MS. As compared to peptide mapping, three and seven glycation sites were located in the primary structure of LA-ketose and LA-aldose conjugates, respectively. On the other hand, the antioxidant activities of protein-sugar conjugates and their peptic hydrolysates were investigated by 1,1-diphenyl-2-picrylhydrazyl radical scavenging method. The antioxidant activities of proteins/peptides glycated with rare sugars were significantly higher than those modified with the control sugars. The results indicated that the glycation degree and position were not markedly different between rare sugar and corresponding control sugar, but the antioxidant properties of protein and its hydrolysate were significantly enhanced by modifying with rare sugar.

Blood Test: Hemoglobin A1C

Science.gov (United States)

... Why Are Hemoglobin A1c Tests Done? When a child has diabetes, hemoglobin A1c levels are followed to see how well medicines are working. If a child with diabetes has a high hemoglobin A1c level, it may ...

Hemoglobin estimation by the HemoCue® portable hemoglobin photometer in a resource poor setting

Directory of Open Access Journals (Sweden)

Idriss Ali

2011-04-01

Full Text Available Abstract Background In resource poor settings where automated hematology analyzers are not available, the Cyanmethemoglobin method is often used. This method though cheaper, takes more time. In blood donations, the semi-quantitative gravimetric copper sulfate method which is very easy and inexpensive may be used but does not provide an acceptable degree of accuracy. The HemoCue® hemoglobin photometer has been used for these purposes. This study was conducted to generate data to support or refute its use as a point-of-care device for hemoglobin estimation in mobile blood donations and critical care areas in health facilities. Method EDTA blood was collected from study participants drawn from five groups: pre-school children, school children, pregnant women, non-pregnant women and men. Blood collected was immediately processed to estimate the hemoglobin concentration using three different methods (HemoCue®, Sysmex KX21N and Cyanmethemoglobin. Agreement between the test methods was assessed by the method of Bland and Altman. The Intraclass correlation coefficient (ICC was used to determine the within subject variability of measured hemoglobin. Results Of 398 subjects, 42% were males with the overall mean age being 19.4 years. The overall mean hemoglobin as estimated by each method was 10.4 g/dl for HemoCue, 10.3 g/dl for Sysmex KX21N and 10.3 g/dl for Cyanmethemoglobin. Pairwise analysis revealed that the hemoglobin determined by the HemoCue method was higher than that measured by the KX21N and Cyanmethemoglobin. Comparing the hemoglobin determined by the HemoCue to Cyanmethemoglobin, the concordance correlation coefficient was 0.995 (95% CI: 0.994-0.996, p Conclusion Hemoglobin determined by the HemoCue method is comparable to that determined by the other methods. The HemoCue photometer is therefore recommended for use as on-the-spot device for determining hemoglobin in resource poor setting.

Determination of Mean Glycated Haemoglobin in Healthy Adults of a Local Population

International Nuclear Information System (INIS)

Nida, S.; Ijaz, A.; Aleef, H.; Khan, D. A.; Khan, M. Q. A.; Abbasi, M.

2017-01-01

Objective: To determine the mean hemoglobin HbA1C levels of disease-free adults in a local population and its optimum cutoff for the diagnosis of diabetes. Study Design: Cross-sectional study. Place and Duration of Study: Department of Chemical Pathology and Endocrinology, Armed Forces Institute of Pathology, Rawalpindi, from January to September 2015. Methodology: Healthy subjects aged 18 years and above of either gender were recruited from local population. Pregnant ladies and individuals with known diabetes, chronic kidney disease, chronic liver disease, congestive cardiac failure, anemia, hemoglobinopathies, mental illness and individuals on glucocorticoid therapy were excluded. Fasting plasma glucose (FPG) or 2-hour plasma glucose (2-h PG) was analyzed using hexokinase methodology and glycated hemoglobin (Hb A1C) was also analyzed using turbidimetric inhibition immunoassay technique. Receiver operating characteristic (ROC) curves were plotted. Differences among the groups were tested by one-way ANOVA, and p <0.05 was considered statistically significant. Results: Among 558 subjects, 88.8% (496) were normoglycaemic (NG), 5.7% (32) were with impaired glucose fasting (IFG), and 5.4% (30) were diagnosed with diabetes mellitus (DM). A1C was 5.00 0.44% in NG and 6.28 +-1.16% in diabetics. FPG in NG was 4.55 +-0.95 mmol/L and in diabetics was 8.28 1.78 mmol/L. The optimal HbA1C cutoff value for diagnosis of DM was at 6.05% (AUC 0.827 95% CI 0.732 to 0.923, p <=0.05 with its sensitivity of 53.3% and specificity of 98.5%. However, HbA1C showed suboptimal sensitivity and specificity for prediabetes. Conclusion: The mean HbAIC and cutoff point for diabetes in the study population is 5.07 +-0.58% and 6.05%, respectively (AUC 0.827, 95% CI: 0.732 to 0.923, p<0.001) with 53.3% sensitivity and 98.5% specificity. (author)

Determination Of Ph Including Hemoglobin Correction

Science.gov (United States)

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.

Fisetin lowers methylglyoxal dependent protein glycation and limits the complications of diabetes.

Directory of Open Access Journals (Sweden)

Pamela Maher

Full Text Available The elevated glycation of macromolecules by the reactive dicarbonyl and α-oxoaldehyde methylglyoxal (MG has been associated with diabetes and its complications. We have identified a rare flavone, fisetin, which increases the level and activity of glyoxalase 1, the enzyme required for the removal of MG, as well as the synthesis of its essential co-factor, glutathione. It is shown that fisetin reduces two major complications of diabetes in Akita mice, a model of type 1 diabetes. Although fisetin had no effect on the elevation of blood sugar, it reduced kidney hypertrophy and albuminuria and maintained normal levels of locomotion in the open field test. This correlated with a reduction in proteins glycated by MG in the blood, kidney and brain of fisetin-treated animals along with an increase in glyoxalase 1 enzyme activity and an elevation in the expression of the rate-limiting enzyme for the synthesis of glutathione, a co-factor for glyoxalase 1. The expression of the receptor for advanced glycation end products (RAGE, serum amyloid A and serum C-reactive protein, markers of protein oxidation, glycation and inflammation, were also increased in diabetic Akita mice and reduced by fisetin. It is concluded that fisetin lowers the elevation of MG-protein glycation that is associated with diabetes and ameliorates multiple complications of the disease. Therefore, fisetin or a synthetic derivative may have potential therapeutic use for the treatment of diabetic complications.

Fisetin Lowers Methylglyoxal Dependent Protein Glycation and Limits the Complications of Diabetes

Science.gov (United States)

Maher, Pamela; Dargusch, Richard; Ehren, Jennifer L.; Okada, Shinichi; Sharma, Kumar; Schubert, David

2011-01-01

The elevated glycation of macromolecules by the reactive dicarbonyl and α-oxoaldehyde methylglyoxal (MG) has been associated with diabetes and its complications. We have identified a rare flavone, fisetin, which increases the level and activity of glyoxalase 1, the enzyme required for the removal of MG, as well as the synthesis of its essential co-factor, glutathione. It is shown that fisetin reduces two major complications of diabetes in Akita mice, a model of type 1 diabetes. Although fisetin had no effect on the elevation of blood sugar, it reduced kidney hypertrophy and albuminuria and maintained normal levels of locomotion in the open field test. This correlated with a reduction in proteins glycated by MG in the blood, kidney and brain of fisetin-treated animals along with an increase in glyoxalase 1 enzyme activity and an elevation in the expression of the rate-limiting enzyme for the synthesis of glutathione, a co-factor for glyoxalase 1. The expression of the receptor for advanced glycation end products (RAGE), serum amyloid A and serum C-reactive protein, markers of protein oxidation, glycation and inflammation, were also increased in diabetic Akita mice and reduced by fisetin. It is concluded that fisetin lowers the elevation of MG-protein glycation that is associated with diabetes and ameliorates multiple complications of the disease. Therefore, fisetin or a synthetic derivative may have potential therapeutic use for the treatment of diabetic complications. PMID:21738623

Hemoglobin estimation by the HemoCue® portable hemoglobin photometer in a resource poor setting.

Science.gov (United States)

Nkrumah, Bernard; Nguah, Samuel Blay; Sarpong, Nimako; Dekker, Denise; Idriss, Ali; May, Juergen; Adu-Sarkodie, Yaw

2011-04-21

In resource poor settings where automated hematology analyzers are not available, the Cyanmethemoglobin method is often used. This method though cheaper, takes more time. In blood donations, the semi-quantitative gravimetric copper sulfate method which is very easy and inexpensive may be used but does not provide an acceptable degree of accuracy. The HemoCue® hemoglobin photometer has been used for these purposes. This study was conducted to generate data to support or refute its use as a point-of-care device for hemoglobin estimation in mobile blood donations and critical care areas in health facilities. EDTA blood was collected from study participants drawn from five groups: pre-school children, school children, pregnant women, non-pregnant women and men. Blood collected was immediately processed to estimate the hemoglobin concentration using three different methods (HemoCue®, Sysmex KX21N and Cyanmethemoglobin). Agreement between the test methods was assessed by the method of Bland and Altman. The Intraclass correlation coefficient (ICC) was used to determine the within subject variability of measured hemoglobin. Of 398 subjects, 42% were males with the overall mean age being 19.4 years. The overall mean hemoglobin as estimated by each method was 10.4 g/dl for HemoCue, 10.3 g/dl for Sysmex KX21N and 10.3 g/dl for Cyanmethemoglobin. Pairwise analysis revealed that the hemoglobin determined by the HemoCue method was higher than that measured by the KX21N and Cyanmethemoglobin. Comparing the hemoglobin determined by the HemoCue to Cyanmethemoglobin, the concordance correlation coefficient was 0.995 (95% CI: 0.994-0.996, p < 0.001). The Bland and Altman's limit of agreement was -0.389 - 0.644 g/dl with the mean difference being 0.127 (95% CI: 0.102-0.153) and a non-significant difference in variability between the two measurements (p = 0.843). After adjusting to assess the effect of other possible confounders such as sex, age and category of person, there was no

Nonlinear photoacoustic spectroscopy of hemoglobin

Energy Technology Data Exchange (ETDEWEB)

Danielli, Amos; Maslov, Konstantin; Favazza, Christopher P.; Xia, Jun; Wang, Lihong V., E-mail: LHWANG@WUSTL.EDU [Optical Imaging Laboratory, Department of Biomedical Engineering, Washington University in St. Louis, One Brookings Drive, St. Louis, Missouri 63130 (United States)

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.

Nonlinear photoacoustic spectroscopy of hemoglobin.

Science.gov (United States)

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.

Nonlinear photoacoustic spectroscopy of hemoglobin

International Nuclear Information System (INIS)

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

2015-01-01

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

EPR spectral changes of nitrosil hemes and their relation to the hemoglobin T-R transition

International Nuclear Information System (INIS)

Louro, S.R.W.; Ribeiro, P.C.; Bemski, G.

1980-09-01

EPR spectra of nitrosil-hemes were used to study the quaternary structure of hemoglobin. Human adult hemoglobin has been titrated with nitric oxide at pH 7.0 and 25 0 C. After the equilibration of NO among the α and β subunits the samples were frozen for EPR measurements. The spectra were fitted by linear combinations of three standard signals: the first arising from NO - β hemes and the other two arising from NO - α hemes of molecules in the high and low affinity conformations. The fractional amounts of α subunits exhibiting the high affinity spectrum fitted the two-state model with L = 7 x 10 6 , and csup(α) sub(NO) and csup(β) sub(NO) approximately 0.01. Hemoglobin has been marked with nitric oxide at one chain using low-saturation amounts of nitric oxide. The EPR spectra were studied as a function of oxygen saturation. Linear combinations of the three standard signals above fitted these spectra. The fractions of molecules exhibiting the high affinity spectrum fitted the two-state model with L = 7 x 10 6 , csub(O 2 ) = 0.0033 and csup(α) sub(NO) = 0.08, instead of csup(α) sub(NO) = 0.01.Thus, the two state model is not adequate to describe the conformational transition of these hybrids. The results are evidence of the nonequivalence between oxygen and nitric oxide as ligands. (Author) [pt

Cross-Linking in Collagen by Nonenzymatic Glycation Increases the Matrix Stiffness in Rabbit Achilles Tendon

OpenAIRE

Reddy, G. Kesava

2004-01-01

Nonenzymatic glycation of connective tissue matrix proteins is a major contributor to the pathology of diabetes and aging. Previously the author and colleagues have shown that nonenzymatic glycation significantly enhances the matrix stability in the Achilles tendon (Reddy et al., 2002, Arch. Biochem. Biophys., 399, 174–180). The present study was designed to gain further insight into glycation-induced collagen cross-linking and its relationship to matrix stiffness in the rabbit Achilles tendo...

Fluorescence lifetime measurements of native and glycated human serum albumin and bovine serum albumin

Science.gov (United States)

Joshi, Narahari V.; Joshi, Virgina O. d.; Contreras, Silvia; Gil, Herminia; Medina, Honorio; Siemiarczuk, Aleksander

1999-05-01

Nonenzymatic glycation, also known as Maillard reaction, plays an important role in the secondary complications of the diabetic pathology and aging, therefore, human serum albumin (HSA) and bovine serum albumin (BSA) were glycated by a conventional method in our laboratory using glucose as the glycating agent. Fluorescence lifetime measurements were carried out with a laser strobe fluorometer equipped with a nitrogen/dye laser and a frequency doubler as a pulsed excitation source. The samples were excited at 295 nm and the emission spectra were recorded at 345 nm. The obtained decay curves were tried for double and triple exponential functions. It has been found that the shorter lifetime increases for glycated proteins as compared with that of the native ones. For example, in the case of glycated BSA the lifetime increased from 1.36 ns to 2.30 ns. Similarly, for HSA, the lifetime increases from 1.58 ns to 2.26 ns. Meanwhile, the longer lifetime changed very slightly for both proteins (from 6.52 ns to 6.72 ns). The increase in the lifetime can be associated with the environmental effect; originated from the attachment of glucose to some lysine residues. A good example is Trp 214 which is in the cage of Lys 225, Lys 212, Lys 233, Lys 205, Lys 500, Lys 199 and Lys 195. If fluorescence lifetime technique is calibrated and properly used it could be employed for assessing glycation of proteins.

Reference interval determination of hemoglobin fractions in umbilical cord and placental blood by capillary electrophoresis.

Science.gov (United States)

Bó, Suzane Dal; de Oliveira Lemos, Fabiane Kreutz; Pedrazzani, Fabiane Spagnol; Cagliari, Cláudia Rosa; Scotti, Luciana

2016-04-01

Umbilical cord and placental blood (UCPB) is a rich source of hematopoietic stem cells widely used to treat diseases that did not have effective treatments until recently. Umbilical cord and placental blood banks (UCPBBs) are needed to be created to store UCPB. UCPB is collected immediately after birth, processed, and frozen until infusion. Detection of abnormal hemoglobins is one of UCPB screening tests available. The objective of the present study was to determine the reference interval for HbA, HbF, and HbA2 in UCPB using capillary electrophoresis. Methods: Observational retrospective study of UCPB samples undergoing hemoglobin electrophoresis was performed between April 2012 and May 2013. We analyzed 273 UCPB samples. All cords met the criteria of BrasilCORD. We found 19.9% (10.5–36.7%) for HbA, 80.1% (62.7–89.4%) for HbF, and 0.1% (0.0–0.6%) for HbA2. Data were expressed as median (P2.5–P97.5). Establishing specific reference intervals is the best option for most tests because such ranges reflect the status of the population in which the tests will be applied. The use of appropriate reference intervals ensures that clinical labs provide reliable information, thus enabling clinicians to correctly interpret results and choose the best approach for the target population.

The Preventive Effect of L-Lysine on Lysozyme Glycation in Type 2 Diabetes

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Hossein Mirmiranpour

2016-01-01

Full Text Available Lysozyme is a bactericidal enzyme whose structure and functions change in diabetes. Chemical chaperones are small molecules including polyamines (e.g. spermine, amino acids (e.g. L-lysine and polyols (e.g. glycerol. They can improve protein conformation in several stressful conditions such as glycation. In this study, the authors aimed to observe the effect of L-lysine as a chemical chaperone on structure and function of glycated lysozyme. In this study, in vitro and in vivo effects of L-lysine on lysozyme glycation were investigated. Lysozyme was incubated with glucose and/or L-lysine, followed by an investigation of its structure by electrophoresis, fluorescence spectroscopy, and circular dichroism spectroscopy and also assessment of its bactericidal activity against M. lysodeikticus. In the clinical trial, patients with type 2 diabetes mellitus (T2DM were randomly divided into two groups of 25 (test and control. All patients received metformin and glibenclamide for a three months period. The test group was supplemented with 3 g/day of L-lysine. The quantity and activity of lysozyme and other parameters were then measured. Among the test group, L-lysine was found to reduce the advanced glycation end products (AGEs in the sera of patients with T2DM and in vitro condition. This chemical chaperone reversed the alteration in lysozyme structure and function due to glycation and resulted in increased lysozyme activity. Structure and function of glycated lysozyme are significantly improved by l-lysine; therefore it can be considered an effective therapeutic supplementation in T2DM, decreasing the risk of infection in these patients.

Hemoglobin Variants: Biochemical Properties and Clinical Correlates

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Thom, Christopher S.; Dickson, Claire F.; Gell, David A.; Weiss, Mitchell J.

2013-01-01

Diseases affecting hemoglobin synthesis and function are extremely common worldwide. More than 1000 naturally occurring human hemoglobin variants with single amino acid substitutions throughout the molecule have been discovered, mainly through their clinical and/or laboratory manifestations. These variants alter hemoglobin structure and biochemical properties with physiological effects ranging from insignificant to severe. Studies of these mutations in patients and in the laboratory have produced a wealth of information on hemoglobin biochemistry and biology with significant implications for hematology practice. More generally, landmark studies of hemoglobin performed over the past 60 years have established important paradigms for the disciplines of structural biology, genetics, biochemistry, and medicine. Here we review the major classes of hemoglobin variants, emphasizing general concepts and illustrative examples. PMID:23388674

Bioprospecting the Curculigoside-Cinnamic Acid-Rich Fraction from Molineria latifolia Rhizome as a Potential Antioxidant Therapeutic Agent

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Der Jiun Ooi

2016-06-01

Full Text Available Increasing evidence from both experimental and clinical studies depicts the involvement of oxidative stress in the pathogenesis of various diseases. Specifically, disruption of homeostatic redox balance in accumulated body fat mass leads to obesity-associated metabolic syndrome. Strategies for the restoration of redox balance, potentially by exploring potent plant bioactives, have thus become the focus of therapeutic intervention. The present study aimed to bioprospect the potential use of the curculigoside-cinnamic acid-rich fraction from Molineria latifolia rhizome as an antioxidant therapeutic agent. The ethyl acetate fraction (EAF isolated from M. latifolia rhizome methanolic extract (RME contained the highest amount of phenolic compounds, particularly curculigoside and cinnamic acid. EAF demonstrated glycation inhibitory activities in both glucose- and fructose-mediated glycation models. In addition, in vitro chemical-based and cellular-based antioxidant assays showed that EAF exhibited high antioxidant activities and a protective effect against oxidative damage in 3T3-L1 preadipocytes. Although the efficacies of individual phenolics differed depending on the structure and concentration, a correlational study revealed strong correlations between total phenolic contents and antioxidant capacities. The results concluded that enriched phenolic contents in EAF (curculigoside-cinnamic acid-rich fraction contributed to the overall better reactivity. Our data suggest that this bioactive-rich fraction warrants therapeutic potential against oxidative stress-related disorders.

High affinity hemoglobin and Parkinson's disease.

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Graham, Jeffrey; Hobson, Douglas; Ponnampalam, Arjuna

2014-12-01

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra (SN) region of the midbrain. Oxidative damage in this region has been shown to play an important role in the pathogenesis of this disease. Human neurons have been discovered to contain hemoglobin, with an increased concentration seen in the neurons of the SN. High affinity hemoglobin is a clinical entity resulting from mutations that create a functional increase in the binding of hemoglobin to oxygen and an inability to efficiently unload it to tissues. This can result in a number of metabolic compensatory changes, including an elevation in circulating hemoglobin and an increase in the molecule 2,3-diphosphoglycerate (2,3-DPG). Population based studies have revealed that patients with PD have elevated hemoglobin as well as 2,3-DPG levels. Based on these observations, we hypothesize that the oxidative damage seen in PD is related to an underlying high affinity hemoglobin subtype. Copyright © 2014 Elsevier Ltd. All rights reserved.

Advanced glycation end products induce differential structural modifications and fibrillation of albumin

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Awasthi, Saurabh; Sankaranarayanan, Kamatchi; Saraswathi, N. T.

2016-06-01

Glycation induced amyloid fibrillation is fundamental to the development of many neurodegenerative and cardiovascular complications. Excessive non-enzymatic glycation in conditions such as hyperglycaemia results in the increased accumulation of advanced glycation end products (AGEs). AGEs are highly reactive pro-oxidants, which can lead to the activation of inflammatory pathways and development of oxidative stress. Recently, the effect of non-enzymatic glycation on protein structure has been the major research area, but the role of specific AGEs in such structural alteration and induction of fibrillation remains undefined. In this study, we determined the specific AGEs mediated structural modifications in albumin mainly considering carboxymethyllysine (CML), carboxyethyllysine (CEL), and argpyrimidine (Arg-P) which are the major AGEs formed in the body. We studied the secondary structural changes based on circular dichroism (CD) and spectroscopic analysis. The AGEs induced fibrillation was determined by Congo red binding and examination of scanning and transmission electron micrographs. The amyloidogenic regions in the sequence of BSA were determined using FoldAmyloid. It was observed that CEL modification of BSA leads to the development of fibrillar structures, which was evident from both secondary structure changes and TEM analysis.

Characteristic emission in glutaraldehyde polymerized hemoglobin

International Nuclear Information System (INIS)

Ma Li; Wang Xiaojun

2011-01-01

Hemoglobin with different modifications has been investigated using spectroscopic techniques. A new emission at around 371 nm has been observed under excitation of 305 nm from glutaraldehyde polymerized human hemoglobin. Intensity and peak position of the emission are dependent on both oxidation state and ligand environment and the emission has been identified from the hemoglobin oligomer.

Beyond genetic factors in familial amyloidotic polyneuropathy: protein glycation and the loss of fibrinogen's chaperone activity.

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Gonçalo da Costa

Full Text Available Familial amyloidotic polyneuropathy (FAP is a systemic conformational disease characterized by extracellular amyloid fibril formation from plasma transthyretin (TTR. This is a crippling, fatal disease for which liver transplantation is the only effective therapy. More than 80 TTR point mutations are associated with amyloidotic diseases and the most widely accepted disease model relates TTR tetramer instability with TTR point mutations. However, this model fails to explain two observations. First, native TTR also forms amyloid in systemic senile amyloidosis, a geriatric disease. Second, age at disease onset varies by decades for patients bearing the same mutation and some mutation carrier individuals are asymptomatic throughout their lives. Hence, mutations only accelerate the process and non-genetic factors must play a key role in the molecular mechanisms of disease. One of these factors is protein glycation, previously associated with conformational diseases like Alzheimer's and Parkinson's. The glycation hypothesis in FAP is supported by our previous discovery of methylglyoxal-derived glycation of amyloid fibrils in FAP patients. Here we show that plasma proteins are differentially glycated by methylglyoxal in FAP patients and that fibrinogen is the main glycation target. Moreover, we also found that fibrinogen interacts with TTR in plasma. Fibrinogen has chaperone activity which is compromised upon glycation by methylglyoxal. Hence, we propose that methylglyoxal glycation hampers the chaperone activity of fibrinogen, rendering TTR more prone to aggregation, amyloid formation and ultimately, disease.

Radio-ligand immunoassay for human hemoglobin variants

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Javid, J.; Pettis, P.K.; Miller, J.E.

1981-01-01

A quantitative method is described for the individual assay of human hemoglobin variants occurring singly or in mixture. The hemoglobin to be assayed is bound to specific antibody; the immune complex is attached to protein A-containing S. aureus and removed from the mixture. The hemoglobin thus isolated is quantified by its ability to bind radiolabeled haptoglobin. The technique is accurate and distinguishes among the 4 hemoglobins tested, namely Hb A, S, C and F. It has the advantage over conventional radioimmunoassay that a single probe, radiolabeled haptoglobin, is needed for the specific assay of any hemoglobin. (Auth.)

Serum glycated albumin is inversely influenced by fat mass and visceral adipose tissue in Chinese with normal glucose tolerance.

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Feifei Wang

Full Text Available BACKGROUND: Recent studies have revealed that body mass index (BMI inversely influenced serum glycated albumin (GA, which may cause an underestimation of GA-monitored short-term hyperglycemic control. OBJECTIVE: This study was to investigate the association between anthropometric variables (BMI and waist circumference (W and accurate adiposity variables (percentage of body fat (%fat, fat mass, free fat mass (FFM, subcutaneous fat area (SFA, and visceral fat area (VFA with serum GA. DESIGN: A total of 2563 subjects (1037 men, 593 premenopausal women, and 933 postmenopausal women with normal glucose tolerance underwent bioelectrical impedance body fat content measurement and magnetic resonance imaging. Serum GA and absolute value of GA (aGA were measured by enzymatic assay. RESULTS: Compared to the BMI <25.0 kg/m(2 group, the BMI ≥25.0 kg/m(2 group had significantly higher fasting plasma glucose, glycated hemoglobin A1c, and body fat parameters including W, %fat, fat mass, FFM, SFA, and VFA, but significantly lower aGA, and GA in all the three sex- and menopause-stratified groups (all P<0.05. GA decreased with the increment of fat mass for all three groups (all P for trend <0.001. In the same BMI category, men and postmenopausal women with elevated %fat (men, ≥25%; women, ≥35% still had significantly lower GA than those with normal %fat (men, <25%; women, <35% (all P<0.05. Multiple stepwise regression showed that %fat, fat mass, and VFA were independently associated with GA. CONCLUSIONS: Serum GA was inversely influenced by fat mass and visceral adipose tissue in Chinese with normal glucose tolerance.

Glycation of human cortical and cancellous bone captures differences in the formation of Maillard reaction products between glucose and ribose.

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Grażyna E Sroga

Full Text Available To better understand some aspects of bone matrix glycation, we used an in vitro glycation approach. Within two weeks, our glycation procedures led to the formation of advanced glycation end products (AGEs at the levels that corresponded to approx. 25-30 years of the natural in vivo glycation. Cortical and cancellous bones from human tibias were glycated in vitro using either glucose (glucosylation or ribose (ribosylation. Both glucosylation and ribosylation led to the formation of higher levels of AGEs and pentosidine (PEN in cancellous than cortical bone dissected from all tested donors (young, middle-age and elderly men and women. More efficient glycation of bone matrix proteins in cancellous bone most likely depended on the higher porosity of this tissue, which facilitated better accessibility of the sugars to the matrix proteins. Notably, glycation of cortical bone from older donors led to much higher AGEs levels as compared to young donors. Such efficient in vitro glycation of older cortical bone could result from aging-related increase in porosity caused by the loss of mineral content. In addition, more pronounced glycation in vivo would be driven by elevated oxidation processes. Interestingly, the levels of PEN formation differed pronouncedly between glucosylation and ribosylation. Ribosylation generated very high levels of PEN (approx. 6- vs. 2.5-fold higher PEN level than in glucosylated samples. Kinetic studies of AGEs and PEN formation in human cortical and cancellous bone matrix confirmed higher accumulation of fluorescent crosslinks for ribosylation. Our results suggest that in vitro glycation of bone using glucose leads to the formation of lower levels of AGEs including PEN, whereas ribosylation appears to support a pathway toward PEN formation. Our studies may help to understand differences in the progression of bone pathologies related to protein glycation by different sugars, and raise awareness for excessive sugar

SERUM MAGNESIUM, LIPID PROFILE AND GLYCATED HAEMOGLOBIN IN DIABETIC RETINOPATHY

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Sunanda Vusikala

2016-07-01

Full Text Available BACKGROUND Diabetic retinopathy is one of the important microvascular complications of diabetes mellitus of long duration. Alterations in trace metals like magnesium and lipid profile was observed in diabetic retinopathy with hyperglycaemic status. AIM The study was taken up to assess the role of magnesium, lipid profile and glycated haemoglobin in diabetic retinopathy. MATERIALS AND METHODS A total of 80 subjects between 40-65 years were included in the study. Group 1 includes 20 age and sex matched healthy controls. Group 2 includes 30 cases of Diabetes mellitus without retinopathy. Group 3 includes 30 cases of Diabetes mellitus with retinopathy. RESULTS Magnesium was found to be significantly low in the diabetic group with retinopathy. Serum cholesterol and triglycerides were significantly elevated in the diabetic group with retinopathy. Fasting and Postprandial plasma glucose and glycated haemoglobin (HbA1c levels confirmed the glycaemic status of each of the groups. CONCLUSIONS Hypomagnesemia, hypercholesterolaemia, hypertriglyceridemia was observed in diabetic retinopathy along with increased levels of glycated haemoglobin in our study.

Relationship of Baseline Hemoglobin Level with Serum Ferritin, Postphlebotomy Hemoglobin Changes, and Phlebotomy Requirements among HFE C282Y Homozygotes

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Seyed Ali Mousavi

2015-01-01

Full Text Available 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.

Relationship of Baseline Hemoglobin Level with Serum Ferritin, Postphlebotomy Hemoglobin Changes, and Phlebotomy Requirements among HFE C282Y Homozygotes

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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 (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 (baseline hemoglobin. Conclusion. Dividing C282Y-homozygous patients into just two subgroups according to the degree of baseline SF elevation may obscure important subgroup variations. PMID:26380265

Current therapeutic interventions in the glycation pathway: evidence from clinical studies.

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Engelen, L; Stehouwer, C D A; Schalkwijk, C G

2013-08-01

The increased formation of advanced glycation endproducts (AGEs) constitutes a potential mechanism of hyperglycaemia-induced micro- and macrovascular disease in diabetes. In vitro and animal experiments have shown that various interventions can inhibit formation and/or actions of AGEs, in particular the specific AGE inhibitor aminoguanidine and the AGEs crosslink breaker alagebrium, and the B vitamins pyridoxamine and thiamine, and the latter's synthetic derivative, benfotiamine. The potential clinical value of these interventions, however, remains to be established. The present review provides, from the clinical point of view, an overview of current evidence on interventions in the glycation pathway relating to (i) the clinical benefits of specific AGE inhibitors and AGE breakers and (ii) the potential AGE-inhibiting effects of therapies developed for purposes unrelated to the glycation pathway. We found that safety and/or efficacy in clinical studies with the specific AGE inhibitor, aminoguanidine and the AGE breaker, alagebrium, appeared to be a concern. The clinical evidence on the potential AGE-inhibiting effects of B vitamins is still limited. Finally, current evidence for AGE inhibition by therapies developed for purposes unrelated to glycation is limited due to a large heterogeneity in study designs and/or measurement techniques, which have often been sub-optimal. We conclude that, clinical evidence on interventions to inhibit formation and/or action of AGEs is currently weak and unconvincing. © 2012 Blackwell Publishing Ltd.

A review of variant hemoglobins interfering with hemoglobin A1c measurement.

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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. 2009 Diabetes Technology Society.

Effects on Diabetes Medications, Weight and Glycated Hemoglobin Among Adult Patients With Obesity and Type 2 Diabetes: 6-Month Observations From a Full Meal Replacement, Low-Calorie Diet Weight Management Program.

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Shiau, Judy Y; So, Derek Y F; Dent, Robert R

2018-02-01

A 6-month weight-management program with full meal replacement, low-calorie diet (full MR-LCD) (900 kcal/day for 6 to 12 weeks) follows a protocol for patients with diabetes for decreasing or discontinuing weight-gaining diabetes medications first (Group WG) and then titrating weight-neutral medications (Group WN). This is a retrospective cohort study (1992 to 2009) of weight, glycemic control and diabetes medications changes in 317 patients with obesity and type 2 diabetes who were taking medications. Group WG and Group WN were similar at baseline, except that glycated hemoglobin (A1C) levels were significantly lower in Group WN (7.5% vs. 6.6%; p<0.001). At 6 months, both groups had lost 16% of their weight, and the decreases or discontinuations of medications were 92.1% sulfonureas, 86.5% insulins, 78.8% thiazolidinediones, 77.8% alpha-glucosidase inhibitors, 50% meglitinides, 33.3% dipeptidyl peptidase-4 (DPP-4) inhibitors and 32.8% metformin. At 6 months, compared with baseline, A1C levels improved in Group WG and Group WN (6-month A1C levels 6.7% and 5.8%, respectively; p<0.0001), and Group WN had significantly better A1C levels than Group WG. At 6 months, 30% of patients were no longer taking diabetes medications and had significantly better percentages of weight loss compared with those taking medications (18.6% vs. 16%; p=0.002); both groups had improved glycemic control at 6 months (A1C 6.0% vs. A1C 6.6%; NS). In patients with obesity and type 2 diabetes taking medications, a full MR-LCD program appears to be safe and includes improvement in A1C levels. At 6 months, the percentage of weight loss can be significantly better in patients who no longer require diabetes medications, and A1C levels are best controlled in patients who are on WN medications. Copyright © 2017 Diabetes Canada. Published by Elsevier Inc. All rights reserved.

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

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Sultan Ayoub Meo

2015-11-01

Full Text Available 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.

Characterization of hemoglobin-benzo[a]pyrene adducts

International Nuclear Information System (INIS)

Haugen, D.A.; Myers, S.R.

1987-01-01

Cultures of Syrian hamster embryo (SHE) cells were supplemented with human Hb (0.2 mM heme) and [ 3 H]BP (1 μM). After a 24-h incubation, the medium was removed and subjected to cation-exchange liquid chromatography (CM-Sepharose) to resolve hemoglobins from serum proteins in the medium. The BP-treated Hb was subjected to analysis in each of three column chromatographic systems established for isolation and characterization of human hemoglobin and its genetic and post-translationally modified variants. Results demonstrate that hemoglobin-carcinogen adducts can be resolved from native hemoglobin by established conventional and high-performance liquid chromatographic procedures, suggesting the basis for development of general approaches for isolating and characterizing hemoglobin-carcinogen adducts. The results also suggest the basis for a model system in which adducts between carcinogens and human hemoglobin are formed in cultures of mammalian cells or tissues

Using an enzymatic galactose assay to detect lactose glycation extents of two proteins caseinate and soybean protein isolate via the Maillard reaction.

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Wang, Xiao-Peng; Zhao, Xin-Huai

2017-06-01

Glycation of food proteins via the Maillard reaction has been widely studied in the recent years; however, the amount of saccharide connected to proteins is usually not determined. An enzymatic galactose assay was proposed firstly in this study to detect lactose glycation extents of caseinate and soybean protein isolate (SPI) during the Maillard reaction at two temperatures and different times. The separated glycated proteins were hydrolysed to release galactose necessary for the enzymatic assay and glycation calculation. Caseinate and SPI both obtained the highest lactose glycation extents at 100 °C or 121 °C by a reaction time of 180 or 20 min. Short- and long-time reaction resulted in lower glycation extents. During the reaction, three chemical indices (absorbences at 294/490 nm and fluorescence intensities) of reaction mixtures increased continually, but another index reactable NH 2 of glycated proteins showed the opposite trend. In general, changing profiles of the four indices were inconsistent with those profiles of lactose glycation extents of glycated proteins, implying practical limitation of the four indices in studies. This proposed enzymatic assay could directly detect lactose glycation of the two proteins, and thus was more useful than the four chemical indices to monitor glycation of the two proteins. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

Inhibitory effect of gold nanoparticles on the D-ribose glycation of bovine serum albumin

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Liu W

2014-11-01

Full Text Available Weixi Liu,1 Menashi A Cohenford,1–3 Leslie Frost,3 Champika Seneviratne,4 Joel A Dain1 1Department of Chemistry, University of Rhode Island, Kingston, RI, USA; 2Department of Integrated Science and Technology, 3Department of Chemistry, Marshall University, Huntington, WV, USA; 4Department of Chemistry, College of the North Atlantic, Labrador, NL, Canada Abstract: Formation of advanced glycation end products (AGEs by nonenzymatic glycation of proteins is a major contributory factor to the pathophysiology of diabetic conditions including senile dementia and atherosclerosis. This study describes the inhibitory effect of gold nanoparticles (GNPs on the D-ribose glycation of bovine serum albumin (BSA. A combination of analytical methods including ultraviolet–visible spectrometry, high performance liquid chromatography, circular dichroism, and matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF mass spectrometry were used to determine the extent of BSA glycation in the presence of citrate reduced spherical GNPs of various sizes and concentrations. GNPs of particle diameters ranging from 2 nm to 20 nm inhibited BSA’s AGE formation. The extent of inhibition correlated with the total surface area of the nanoparticles. GNPs of highest total surface area yielded the most inhibition whereas those with the lowest total surface area inhibited the formation of AGEs the least. Additionally, when GNPs’ total surface areas were set the same, their antiglycation activities were similar. This inhibitory effect of GNPs on BSA’s glycation by D-ribose suggests that colloidal particles may have a therapeutic application for the treatment of diabetes and conditions that promote hyperglycemia. Keywords: gold nanoparticles, glycation, AGEs, GNPs, BSA

MR Imaging-derived Oxygen-Hemoglobin Dissociation Curves and Fetal-Placental Oxygen-Hemoglobin Affinities.

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Avni, Reut; Golani, Ofra; Akselrod-Ballin, Ayelet; Cohen, Yonni; Biton, Inbal; Garbow, Joel R; Neeman, Michal

2016-07-01

Purpose To generate magnetic resonance (MR) imaging-derived, oxygen-hemoglobin dissociation curves and to map fetal-placental oxygen-hemoglobin affinity in pregnant mice noninvasively by combining blood oxygen level-dependent (BOLD) T2* and oxygen-weighted T1 contrast mechanisms under different respiration challenges. Materials and Methods All procedures were approved by the Weizmann Institutional Animal Care and Use Committee. Pregnant mice were analyzed with MR imaging at 9.4 T on embryonic days 14.5 (eight dams and 58 fetuses; imprinting control region ICR strain) and 17.5 (21 dams and 158 fetuses) under respiration challenges ranging from hyperoxia to hypoxia (10 levels of oxygenation, 100%-10%; total imaging time, 100 minutes). A shorter protocol with normoxia to hyperoxia was also performed (five levels of oxygenation, 20%-100%; total imaging time, 60 minutes). Fast spin-echo anatomic images were obtained, followed by sequential acquisition of three-dimensional gradient-echo T2*- and T1-weighted images. Automated registration was applied to align regions of interest of the entire placenta, fetal liver, and maternal liver. Results were compared by using a two-tailed unpaired Student t test. R1 and R2* values were derived for each tissue. MR imaging-based oxygen-hemoglobin dissociation curves were constructed by nonlinear least square fitting of 1 minus the change in R2*divided by R2*at baseline as a function of R1 to a sigmoid-shaped curve. The apparent P50 (oxygen tension at which hemoglobin is 50% saturated) value was derived from the curves, calculated as the R1 scaled value (x) at which the change in R2* divided by R2*at baseline scaled (y) equals 0.5. Results The apparent P50 values were significantly lower in fetal liver than in maternal liver for both gestation stages (day 14.5: 21% ± 5 [P = .04] and day 17.5: 41% ± 7 [P hemoglobin dissociation curves with a shorter protocol that excluded the hypoxic periods was demonstrated. Conclusion MR imaging

Percutaneous Mitral Valve Repair in Mitral Regurgitation Reduces Cell-Free Hemoglobin and Improves Endothelial Function.

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Christos Rammos

Full Text Available Endothelial dysfunction is predictive for cardiovascular events and may be caused by decreased bioavailability of nitric oxide (NO. NO is scavenged by cell-free hemoglobin with reduction of bioavailable NO up to 70% subsequently deteriorating vascular function. While patients with mitral regurgitation (MR suffer from an impaired prognosis, mechanisms relating to coexistent vascular dysfunctions have not been described yet. Therapy of MR using a percutaneous mitral valve repair (PMVR approach has been shown to lead to significant clinical benefits. We here sought to investigate the role of endothelial function in MR and the potential impact of PMVR.Twenty-seven patients with moderate-to-severe MR treated with the MitraClip® device were enrolled in an open-label single-center observational study. Patients underwent clinical assessment, conventional echocardiography, and determination of endothelial function by measuring flow-mediated dilation (FMD of the brachial artery using high-resolution ultrasound at baseline and at 3-month follow-up. Patients with MR demonstrated decompartmentalized hemoglobin and reduced endothelial function (cell-free plasma hemoglobin in heme 28.9±3.8 μM, FMD 3.9±0.9%. Three months post-procedure, PMVR improved ejection fraction (from 41±3% to 46±3%, p = 0.03 and NYHA functional class (from 3.0±0.1 to 1.9±1.7, p<0.001. PMVR was associated with a decrease in cell free plasma hemoglobin (22.3±2.4 μM, p = 0.02 and improved endothelial functions (FMD 4.8±1.0%, p<0.0001.We demonstrate here that plasma from patients with MR contains significant amounts of cell-free hemoglobin, which is accompanied by endothelial dysfunction. PMVR therapy is associated with an improved hemoglobin decompartmentalization and vascular function.

Hemoglobin of mice with radiation-induced mutations at the hemoglobin loci

Energy Technology Data Exchange (ETDEWEB)

Popp, R A; Stratton, L P; Hawley, D K; Effron, K [Oak Ridge National Lab., TN (USA)

1979-01-15

Chemical analyses were done on the abnormal hemoglobins of the five (101 x SEC)F/sub 1/ offspring of X- irradiated adult SEC mice to determine which hemoglobin genes were expressed in each hemoglobin variant. Three offspring of irradiated SEC males did not express either of the two kinds of ..cap alpha..-chains normally found in all SEC mice. The deficient ..cap alpha..-chain synthesis caused these mice to exhibit an ..cap alpha..-thalassemia similar to human ..cap alpha..-thalassemia. Scanning electron microscopy was used to show that many erythrocytes of mice with ..cap alpha..-thalassemia have bizarre shapes; e.g. many erythrocytes appeared flattened or had thorny projections (acanthocytes). One mutant with a tandem duplication of a segment of chromosome 7 (site of locus determining ..beta..-chain structure) produced twice as much SEC as 101 ..beta..-chain polypeptides. One mutant that probably arose by non-disjunction of chromosome 7's in its unirradiated 101 mother and loss of chromosome 7 from the gamete of its irradiated SEC father did not express the SEC ..beta..-chain gene.

Hemoglobin of mice with radiation-induced mutations at the hemoglobin loci

International Nuclear Information System (INIS)

Popp, R.A.; Stratton, L.P.; Hawley, D.K.; Effron, K.

1979-01-01

Chemical analyses were done on the abnormal hemoglobins of the five (101 x SEC)F 1 offspring of X- irradiated adult SEC mice to determine which hemoglobin genes were expressed in each hemoglobin variant. Three offspring of irradiated SEC males did not express either of the two kinds of α-chains normally found in all SEC mice. The deficient α-chain synthesis caused these mice to exhibit an α-thalassemia similar to human α-thalassemia. Scanning electron microscopy was used to show that many erythrocytes of mice with α-thalassemia have bizarre shapes; e.g. many erythrocytes appeared flattened or had thorny projections (acanthocytes). One mutant with a tandem duplication of a segment of chromosome 7 (site of locus determining β-chain structure) produced twice as much SEC as 101 β-chain polypeptides. One mutant that probably arose by non-disjunction of chromosome 7's in its unirradiated 101 mother and loss of chromosome 7 from the gamete of its irradiated SEC father did not express the SEC β-chain gene. (author)

Accumulation of advanced glycation endproducts reduces chondrocyte-mediated extracellular matrix turnover in human articular cartilage

NARCIS (Netherlands)

Degroot, J.; Verzijl, N.; Jacobs, K. M.; Budde, M.; Bank, R. A.; Bijlsma, J. W.; TeKoppele, J. M.; Lafeber, F. P.

2001-01-01

The prevalence of osteoarthritis (OAs) increases with age and coincides with the accumulation of advanced glycation endproducts (AGEs) in articular cartilage, suggesting that accumulation of glycation products may be involved in the development of OA. This study was designed to examine the effects

Role of protein-bound carbonyl groups in the formation of advanced glycation endproducts.

Science.gov (United States)

Liggins, J; Furth, A J

1997-08-22

Several mechanisms have been postulated for the formation of advanced glycation endproducts (AGEs) from glycated proteins; they all feature protein-bound carbonyl intermediates. Using 2,4-dinitrophenylhydrazine (DNPH), we have detected these intermediates on bovine serum albumin, lysozyme and beta-lactoglobulin after in vitro glycation by glucose or fructose. Carbonyls were formed in parallel with AGE-fluorophores, via oxidative Maillard reactions. Neither Amadori nor Heyns products contributed to the DNPH reaction. Fluorophore and carbonyl yields were much enhanced in lipid-associated proteins, but both groups could also be detected in lipid-free proteins. When pre-glycated proteins were incubated in the absence of free sugar, carbonyl groups were rapidly lost in a first-order reaction, while fluorescence continued to develop beyond the 21 days of incubation. Another unexpected finding was that not all carbonyl groups were blocked by aminoguanidine, although there was complete inhibition of reactions leading to AGE-fluorescence. It is suggested that carbonyls acting as fluorophore precursors react readily with aminoguanidine, while others are resistant to this hydrazine, possibly because they are involved in ring closure. Factors influencing the relative rates of acyclisation and hydrazone formation are discussed, together with possible implications for antiglycation therapy.

Effect of Multiple Mutations in the Hemoglobin- and Hemoglobin-Haptoglobin-Binding Proteins, HgpA, HgpB, and HgpC, of Haemophilus influenzae Type b

OpenAIRE

Morton, Daniel J.; Whitby, Paul W.; Jin, Hongfan; Ren, Zhen; Stull, Terrence L.

1999-01-01

Haemophilus influenzae requires heme for growth and can utilize hemoglobin and hemoglobin-haptoglobin as heme sources. We previously identified two hemoglobin- and hemoglobin-haptoglobin-binding proteins, HgpA and HgpB, in H. influenzae HI689. Insertional mutation of hgpA and hgpB, either singly or together, did not abrogate the ability to utilize or bind either hemoglobin or the hemoglobin-haptoglobin complex. A hemoglobin affinity purification method was used to isolate a protein of approxi...

Diabetes induced testicular dysfunction amelioration by ethyl acetate fraction of hydromethanolic extract of root of Musa paradisiaca L. in streptozotocin-induced diabetic rat

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Kausik Chatterjee

2012-05-01

Full Text Available Objective: To investigate the diabetic therapeutic potentiality and antioxidative efficacy of ethyl acetate fraction of hydro-methanol (40:60 extract of root of Musa paradisiaca Lam. (Musaceae in streptozotocin-induced diabetic rat. Methods: Streptozotocin-induced diabetic state was confirmed by decreased serum insulin level and carbohydrate metabolomics i.e. increased fasting blood glucose level, glycated hemoglobin level and diminished glycogen contents in liver and skeletal muscle. Reproductive homeostasis alteration in diabetes was evaluated by reproductive organo-somatic indices, sperm count, motility and histological analysis of testicular seminiferous tubule along with levels of serum testosterone, testicular cholesterol and seminal vesicular fructose assessment. Oxidative stress in primary and accessory sex organs, and in sperm pellet was assessed by measuring antioxidant enzyme activities along with quantification of free radicals products. Testicular pro-apoptotic Bax-毩 mRNA expression pattern was studied semi-quantitatively by PCR technique. Reverse phase HPLC fingerprinting was performed using methanol and acetonitrile as mobile phase. Results: Oral administration of ethyl acetate fraction at a dose of 20 mg/0.5 mL of distilled water/100 gm body weight twice daily to the diabetic rats for 28 days significantly recovered organo-somatic indices, protected reproductive activities, corrected oxidative stress markers and pro-apoptotic mRNA expression pattern, which were deviated in diabetes mellitus from control level without any type of toxicity. HPLC fingerprinting shows five completely resolved peaks at 毸 max 254 nm and 342 nm. Conclusions: It has a promising antihyperglycaemic and antioxidative activity for curing diabetes induced reproductive disorders in streptozotocin-induced diabetic rat.

Led Astray by Hemoglobin A1c

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Jean Chen MD

2016-01-01

Full Text Available Hemoglobin A1c (A1c is used frequently to diagnose and treat diabetes mellitus. Therefore, it is important be aware of factors that may interfere with the accuracy of A1c measurements. This is a case of a rare hemoglobin variant that falsely elevated a nondiabetic patient’s A1c level and led to a misdiagnosis of diabetes. A 67-year-old male presented to endocrine clinic for further management after he was diagnosed with diabetes based on an elevated A1c of 10.7%, which is approximately equivalent to an average blood glucose of 260 mg/dL. Multiple repeat A1c levels remained >10%, but his home fasting and random glucose monitoring ranged from 92 to 130 mg/dL. Hemoglobin electrophoresis and subsequent genetic analysis diagnosed the patient with hemoglobin Wayne, a rare hemoglobin variant. This variant falsely elevates A1c levels when A1c is measured using cation-exchange high-performance liquid chromatography. When the boronate affinity method was applied instead, the patient’s A1c level was actually 4.7%. Though hemoglobin Wayne is clinically silent, this patient was erroneously diagnosed with diabetes and started on an antiglycemic medication. Due to this misdiagnosis, the patient was at risk of escalation in his “diabetes management” and hypoglycemia. Therefore, it is important that providers are aware of factors that may result in hemoglobin A1c inaccuracy including hemoglobin variants.

Moessbauer study of hemoglobin of diabetes

International Nuclear Information System (INIS)

Li Aiguo; Ni Xinbo; Cai Yingwen; Zhang Guilin; Zhang Hongde; Ge Yongxin

2000-01-01

The hemoglobins from normal adults (Gly-Hb 5%), people infected with diabetes (Gly-Hb 10%) and serious diabetics (Gly-Hb 15%) were investigated by Moessbauer spectroscopy at liquid nitrogen temperature. All the experimental spectra of hemoglobin are composed of three doublets corresponding to oxy-hemoglobin (Oxy-Hb), deoxy-hemoglobin (Deoxy-Hb) and low-spin hemo-chrome (Ls-Hemo) respectively. It is found that Oxy-Hb is decreasing but Deoxy-hb increasing for diabetes. Experimental results also indicate that the line-width of Moessbauer spectra of Oxy-Hb for diabetics is narrower than that for normal adults, showing that while Fe on Oxy-Hb exists in pile-up of some similar states for normal adults, but it becomes in single state for serious diabetes

An Increased Ratio of Glycated Albumin to HbA1c Is Associated with the Degree of Liver Fibrosis in Hepatitis B Virus-Positive Patients

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Hirayuki Enomoto

2014-01-01

Full Text Available Background. In hepatitis B virus- (HBV- positive patients, the relationship between the metabolic variables and histological degree of liver fibrosis has been poorly investigated. Methods. A total of 176 HBV-positive patients were assessed in whom the ratios of glycated albumin-to-glycated hemoglobin (GA/HbA1c were calculated in order to investigate the relationship with the degree of liver fibrosis. Results. The GA/HbA1c ratio increased in association with the severity of fibrosis (METAVIR scores: F0-1: 2.61 ± 0.24, F2: 2.65 ± 0.24, F3: 2.74 ± 0.38, and F4: 2.91 ± 0.63. The GA/HbA1c ratios were inversely correlated with four variables of liver function: the prothrombin time (PT percentage (P<0.0001, platelet count (P<0.0001, albumin value (P<0.0001, and cholinesterase value (P<0.0001. The GA/HbA1c ratio was positively correlated with two well-known markers of liver fibrosis, FIB-4 (P<0.0001 and the AST-to-platelet ratio index (APRI (P<0.0001. Furthermore, the GA/HbA1c showed better correlations with two variables of liver function (PT percentage and cholinesterase value than did FIB-4 and with all four variables than did the APRI. Conclusion. The GA/HbA1c ratio is associated with the degree of liver fibrosis in HBV-positive patients.

Extract of Bauhinia vahlii Shows Antihyperglycemic Activity, Reverses Oxidative Stress, and Protects against Liver Damage in Streptozotocin-induced Diabetic Rats

Science.gov (United States)

Elbanna, Ahmed H.; Nooh, Mohammed M.; Mahrous, Engy A.; Khaleel, Amal E.; Elalfy, Taha S.

2017-01-01

Background: Several studies have affirmed the effectiveness of some Bauhinia plants as antihyperglycemic agents. Objective: We investigated the possible effect of Bauhinia vahlii leaves extract in reducing hyperglycemia and reversing signs of organ damage associated with diabetes in streptozotocin (STZ) rat model. Materials and Methods: Both polar fraction of the B. vahlii leaves (defatted ethanolic extract [DEE]) and nonpolar fraction (n-hexane extract) were evaluated in vitro for α-glucosidase inhibition and 2,2-diphenyl-1-picrylhydrazyl radical scavenging potential. DEE was selected for further in vivo studies and was administered at two doses, i.e., 150 or 300 mg/kg to STZ-diabetic rats for 4 weeks. Results: Only DEE exhibited in vitro antioxidant and antihyperglycemic activities and its oral administration at both dose levels resulted in significant reduction in fasting blood glucose and glycated hemoglobin. Furthermore, signs of oxidative stress as indicated by hepatic reduced glutathione, nitric oxide, and malondialdehyde levels were completely reversed. In addition, histopathological examination and measurement of serum aspartate transaminase and alanine transaminase levels showed that DEE protected the liver from signs of liver pathogenesis when compared to diabetic untreated animals and those treated with metformin. Phytochemical analysis of DEE showed high flavonoids content with quercitrin as the major constituent along with other quercetin glycosides. Conclusion: This study strongly highlights the possible beneficial effect of B. vahlii leaves extract in relieving hyperglycemia and liver damage in STZ-diabetic rats and recommends further investigation of the value of quercetin derivatives in controlling diabetes and ameliorating liver damage associated with it. SUMMARY The polar fraction of the Bauhinia vahlii leaves (defatted ethanolic extract [DEE]) exhibited both in vitro antioxidant activity in 2,2-diphenyl-1-picrylhydrazyl scavenging assay and

A theoretical model for the effects of reduced hemoglobin-oxygen affinity on tumor oxygenation

International Nuclear Information System (INIS)

Kavanagh, Brian D.; Secomb, Timothy W.; Hsu, Richard; Lin, P.-S.; Venitz, Jurgen; Dewhirst, Mark W.

2002-01-01

Purpose: To develop a theoretical model for oxygen delivery to tumors, and to use the model to simulate the effects of changing the affinity of hemoglobin for oxygen on tumor oxygenation. Methods and Materials: Hemoglobin affinity is expressed in terms of P 50 , the partial pressure of oxygen (Po 2 ) at half saturation. Effects of changing P 50 on arterial Po 2 are predicted using an effective vessel approach to describe diffusive oxygen transport in the lungs, assuming fixed systemic oxygen demand and fixed blood flow rate. The decline in oxygen content of blood as it flows through normal tissue before entering the tumor region is assumed fixed. The hypoxic fraction of the tumor region is predicted using a three-dimensional simulation of diffusion from a network of vessels whose geometry is derived from observations of tumor microvasculature in the rat. Results: In air-breathing rats, predicted hypoxic fraction decreases with moderate increases in P 50 , but increases with further increases of P 50 , in agreement with previous experimental results. In rats breathing hyperoxic gases, and in humans breathing either normoxic or hyperoxic gases, increased P 50 is predicted to improve tumor oxygenation. Conclusions: The results support the administration of synthetic agents to increase P 50 during radiation treatment of tumors

Beneficial effects of Psidium guajava leaf extract on diabetic myocardium.

Science.gov (United States)

Soman, Sowmya; Rajamanickam, Chellam; Rauf, Arun A; Indira, Madambath

2013-01-01

Non enzymatic glycosylation (glycation) between reducing sugar and protein results in the formation of advanced glycation end products (AGEs), which is believed to play an important role in diabetes associated cardiovascular complications. Thus agents that inhibit the formation of AGEs are believed to have therapeutic potential against diabetic complications. In the present study we evaluated the antiglycative potential of ethyl acetate fraction of Psidium guajava leaves (PGEt) by administering the extract into streptozotocin induced diabetic rats. Daily administration of the extract for a period of one month significantly decreased the blood glucose, glycated hemoglobin and fructosamine levels in a dose dependent manner. Evaluation of the toxicity markers like SGOT and SGPT revealed the non toxic nature of the extract. Apart from this we evaluated the presence of cardiac isoform of liver alpha 2 macroglobulin, which is a major protein associated with earlier stages of cardiac hypertrophy. SDS-PAGE analysis showed that the level of this protein decreased significantly in extract treated groups compared to diabetic control. These findings support that the administration of PGEt extract may be beneficial for preventing cardiovascular complications associated with diabetes. Copyright © 2011 Elsevier GmbH. All rights reserved.

Two-photon excited fluorescence emission from hemoglobin

Science.gov (United States)

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.

Convergent evolution of hemoglobin switching in jawed and jawless vertebrates.

Science.gov (United States)

Rohlfing, Kim; Stuhlmann, Friederike; Docker, Margaret F; Burmester, Thorsten

2016-02-01

During development, humans and other jawed vertebrates (Gnathostomata) express distinct hemoglobin genes, resulting in different hemoglobin tetramers. Embryonic and fetal hemoglobin have higher oxygen affinities than the adult hemoglobin, sustaining the oxygen demand of the developing organism. Little is known about the expression of hemoglobins during development of jawless vertebrates (Agnatha). We identified three hemoglobin switches in the life cycle of the sea lamprey. Three hemoglobin genes are specifically expressed in the embryo, four genes in the filter feeding larva (ammocoete), and nine genes correspond to the adult hemoglobin chains. During the development from the parasitic to the reproductive adult, the composition of hemoglobin changes again, with a massive increase of chain aHb1. A single hemoglobin chain is expressed constitutively in all stages. We further showed the differential expression of other globin genes: Myoglobin 1 is most highly expressed in the reproductive adult, myoglobin 2 expression peaks in the larva. Globin X1 is restricted to the embryo; globin X2 was only found in the reproductive adult. Cytoglobin is expressed at low levels throughout the life cycle. Because the hemoglobins of jawed and jawless vertebrates evolved independently from a common globin ancestor, hemoglobin switching must also have evolved convergently in these taxa. Notably, the ontogeny of sea lamprey hemoglobins essentially recapitulates their phylogeny, with the embryonic hemoglobins emerging first, followed by the evolution of larval and adult hemoglobins.

Recent advances in α-synuclein functions, advanced glycation, and toxicity: implications for Parkinson's disease.

Science.gov (United States)

Guerrero, Erika; Vasudevaraju, P; Hegde, Muralidhar L; Britton, G B; Rao, K S

2013-04-01

The toxicity of α-synuclein in the neuropathology of Parkinson's disease which includes its hallmark aggregation has been studied scrupulously in the last decade. Although little is known regarding the normal functions of α-synuclein, its association with membrane phospholipids suggests its potential role in signaling pathways. Following extensive evidences for its nuclear localization, we and others recently demonstrated DNA binding activity of α-synuclein that modulates its conformation as well as aggregation properties. Furthermore, we also underscored the similarities among various amyloidogenic proteins involved in neurodegenerative diseases including amyloid beta peptides and tau. Our more recent studies show that α-synuclein is glycated and glycosylated both in vitro and in neurons, significantly affecting its folding, oligomeric, and DNA binding properties. Glycated α-synuclein causes increased genome damage both via its direct interaction with DNA and by increased generation of reactive oxygen species as glycation byproduct. In this review, we discuss the mechanisms of glycation and other posttranslational modifications of α-synuclein, including phosphorylation and nitration, and their role in neuronal death in Parkinson's disease.

THE EFFECTS OF GLYCATION ON THE BINDING OF HUMAN SERUM ALBUMIN TO WARFARIN AND L-TRYPTOPHAN

OpenAIRE

Joseph, K.S.; Hage, David S.

2010-01-01

Diabetes leads to elevated levels of glucose in blood which, in turn, can lead to the non-enzymatic glycation of serum proteins such as human serum albumin (HSA). It has been suggested that this increase in glycation can alter the ability of HSA to bind to drugs and other small solutes. This study used high-performance affinity chromatography (HPAC) to see if there is any significant change related to glycation in the binding of HSA to warfarin and L-tryptophan, which are often used as probe ...

Ovalbumin with Glycated Carboxyl Groups Shows Membrane-Damaging Activity

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Ching-Chia Tang

2017-02-01

Full Text Available The aim of the present study was to investigate whether glycated ovalbumin (OVA showed novel activity at the lipid-water interface. Mannosylated OVA (Man-OVA was prepared by modification of the carboxyl groups with p-aminophenyl α-dextro (d-mannopyranoside. An increase in the number of modified carboxyl groups increased the membrane-damaging activity of Man-OVA on cell membrane-mimicking vesicles, whereas OVA did not induce membrane permeability in the tested phospholipid vesicles. The glycation of carboxyl groups caused a notable change in the gross conformation of OVA. Moreover, owing to their spatial positions, the Trp residues in Man-OVA were more exposed, unlike those in OVA. Fluorescence quenching studies suggested that the Trp residues in Man-OVA were located on the interface binds with the lipid vesicles, and their microenvironment was abundant in positively charged residues. Although OVA and Man-OVA showed a similar binding affinity for lipid vesicles, the lipid-interacting feature of Man-OVA was distinct from that of OVA. Chemical modification studies revealed that Lys and Arg residues, but not Trp residues, played a crucial role in the membrane-damaging activity of Man-OVA. Taken together, our data suggest that glycation of carboxyl groups causes changes in the structural properties and membrane-interacting features of OVA, generating OVA with membrane-perturbing activities at the lipid-water interface.

Evaluation of Polyphenol Anthocyanin-Enriched Extracts of Blackberry, Black Raspberry, Blueberry, Cranberry, Red Raspberry, and Strawberry for Free Radical Scavenging, Reactive Carbonyl Species Trapping, Anti-Glycation, Anti-β-Amyloid Aggregation, and Microglial Neuroprotective Effects

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Hang Ma

2018-02-01

Full Text Available Glycation is associated with several neurodegenerative disorders, including Alzheimer’s disease (AD, where it potentiates the aggregation and toxicity of proteins such as β-amyloid (Aβ. Published studies support the anti-glycation and neuroprotective effects of several polyphenol-rich fruits, including berries, which are rich in anthocyanins. Herein, blackberry, black raspberry, blueberry, cranberry, red raspberry, and strawberry extracts were evaluated for: (1 total phenolic and anthocyanins contents, (2 free radical (DPPH scavenging and reactive carbonyl species (methylglyoxal; MGO trapping, (3 anti-glycation (using BSA-fructose and BSA-MGO models, (4 anti-Aβ aggregation (using thermal- and MGO-induced fibrillation models, and, (5 murine microglia (BV-2 neuroprotective properties. Berry crude extracts (CE were fractionated to yield anthocyanins-free (ACF and anthocyanins-enriched (ACE extracts. The berry ACEs (at 100 μg/mL showed superior free radical scavenging, reactive carbonyl species trapping, and anti-glycation effects compared to their respective ACFs. The berry ACEs (at 100 μg/mL inhibited both thermal- and MGO-induced Aβ fibrillation. In addition, the berry ACEs (at 20 μg/mL reduced H2O2-induced reactive oxygen species production, and lipopolysaccharide-induced nitric oxide species in BV-2 microglia as well as decreased H2O2-induced cytotoxicity and caspase-3/7 activity in BV-2 microglia. The free radical scavenging, reactive carbonyl trapping, anti-glycation, anti-Aβ fibrillation, and microglial neuroprotective effects of these berry extracts warrant further in vivo studies to evaluate their potential neuroprotective effects against AD.

Lack of association of glycated haemoglobin with blood pressure ...

African Journals Online (AJOL)

2013-04-12

Apr 12, 2013 ... Therefore, we examined the relationships of fasting glucose and glycated ... but factors that did associate significantly were age, male gender, rural location, abdominal obesity, alcohol intake .... in continuous variables were.

Nonenzymatic glycation of phosphatidylethanolamine in erythrocyte vesicles

International Nuclear Information System (INIS)

Patkowska, M.J.; Horowitz, M.I.

1986-01-01

Unsealed inside-out and right-side out vesicles were prepared from human red cells. The vesicles were incubated with D-glucose [ 14 C(U)] and sodium cyanoborohydride in phosphate buffer, pH 7.4. After incubation, lipids were extracted with 1-butanol and non-lipid contaminants removed by Sephadex G-25 chromatography. Phosphatidylethanolamine-sorbitol was purified by chromatography on columns of silicic acid and phenylboronate agarose gel. Phospholipase C (B. cereus) liberated phosphoethanolamine-sorbitol (I) which comigrated on TLC with synthetic I prepared by reductive condensation of phosphoethanolamine and D-glucose and also with the product of phospholipase C (B. cereus) hydrolysis of reference phosphatidylethanolamine-sorbitol. Exposure of I to alkaline phosphatase (E. coli) gave P/sub i/ and ethanolamine-sorbitol (II) which comigrated on TLC with synthetic II prepared by reductive condensation of ethanolamine and D-glucose or by phospholipase D hydrolysis of reference phosphatidylethanolamine-sorbitol. These studies demonstrate that vesicular phosphatidylethanolamine can be reductively glycated and illustrate the applicability of both phospholipase C and phospholipase D in characterizing glycated phosphoglycerides

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

Science.gov (United States)

Inada, Shinya; Koga, Masafumi

2017-01-01

We report that glycated albumin (GA) is higher relative to HbA1c in non-diabetic, gastrectomized subjects without anemia, and thus is a sign of oxyhyperglycemia. It is known that gastrectomized subjects are prone to iron-deficiency anemia (IDA), and that the HbA1c levels of subjects with IDA are falsely high. In the present study, the HbA1c and GA levels of gastrectomized subjects with IDA were compared with gastrectomized subjects without anemia. Seven non-diabetic gastrectomized subjects with IDA were enrolled in the present study. Twenty-eight non-diabetic gastrectomized subjects without anemia matched with the subjects with IDA in terms of age, gender, and body mass index were used as the controls. Although there were no significant differences in fasting plasma glucose and OGTT 2-hour plasma glucose (2-h PG) between the two groups, the HbA1c and GA levels in gastrectomized subjects with IDA were significantly higher than the controls. For all of the gastrectomized subjects (n=35), ferritin exhibited a significant negative correlation with HbA1c and GA, and a significant positive correlation with 2-h PG. In addition, the HbA1c and GA levels exhibited a significant negative correlation with the mean corpuscular hemoglobin and hemoglobin. The HbA1c and GA levels in gastrectomized subjects with IDA were significantly higher than those in controls. The high GA levels are attributed to a tendency in which patients with total gastrectomy, who are prone to IDA, are susceptible to postprandial hyperglycemia and reactive hypoglycemia, which in turn leads to large fluctuations in plasma glucose. © 2017 by the Association of Clinical Scientists, Inc.

Small angle X-ray scattering on concentrated hemoglobin solutions

International Nuclear Information System (INIS)

Zinke, M.; Damaschun, G.; Mueller, J.J.; Ruckpaul, K.

1978-01-01

The small-angle X-ray scattering technique was used to determine the intermolecular structure and interaction potentials in oxi-and deoxi-hemoglobin solutions. The pair correlation function obtained by the ZERNICKE-PRINS equation characterizes the intermolecular structure of the hemoglobin molecules. The intermolecular structure is concentration dependent. The hemoglobin molecules have a 'short range order structure' with a range of about 4 molecule diameters at 324 g/l. The potential functions of the hemoglobin-hemoglobin interaction have been determined on the basis of fluid theories. Except for the deoxi-hemoglobin solution having the concentration 370 g/l, the pair interaction consists in a short repulsion and a weak short-range attraction against kT. The potential minimum is between 1.2 - 1.5 nm above the greatest hemoglobin diameter. (author)

Spectroscopic study of gamma irradiated bovine hemoglobin

International Nuclear Information System (INIS)

Maghraby, Ahmed Mohamed; Ali, Maha Anwar

2007-01-01

In the present study, the effects of ionizing radiation of Cs-137 and Co-60 from 4.95 to 743.14 Gy and from 40 Gy to 300 kGy, respectively, on some bovine hemoglobin characteristics were studied. Such an effect was evaluated using electron paramagnetic resonance (EPR) spectroscopy, and infra-red (IR) spectroscopy. Bovine hemoglobin EPR spectra were recorded and analyzed before and after irradiation and changes were explained in detail. IR spectra of unirradiated and irradiated Bovine hemoglobin were recorded and analyzed also. It was found that ionizing radiation may lead to the increase of free radicals production, the decrease in α-helices contents, which reflects the degradation of hemoglobin molecular structure, or at least its incomplete performance. Results also show that the combined application of EPR and FTIR spectroscopy is a powerful tool for determining structural modification of bovine hemoglobin samples exposed to gamma irradiation

Genetic hemoglobin disorders rather than iron deficiency are a major predictor of hemoglobin concentration in women of reproductive age in rural prey Veng, Cambodia.

Science.gov (United States)

Karakochuk, Crystal D; Whitfield, Kyly C; Barr, Susan I; Lamers, Yvonne; Devlin, Angela M; Vercauteren, Suzanne M; Kroeun, Hou; Talukder, Aminuzzaman; McLean, Judy; Green, Timothy J

2015-01-01

Anemia is common in Cambodian women. Potential causes include micronutrient deficiencies, genetic hemoglobin disorders, inflammation, and disease. We aimed to investigate factors associated with anemia (low hemoglobin concentration) in rural Cambodian women (18-45 y) and to investigate the relations between hemoglobin disorders and other iron biomarkers. Blood samples were obtained from 450 women. A complete blood count was conducted, and serum and plasma were analyzed for ferritin, soluble transferrin receptor (sTfR), folate, vitamin B-12, retinol binding protein (RBP), C-reactive protein (CRP), and α1 acid glycoprotein (AGP). Hemoglobin electrophoresis and multiplex polymerase chain reaction were used to determine the prevalence and type of genetic hemoglobin disorders. Overall, 54% of women had a genetic hemoglobin disorder, which included 25 different genotypes (most commonly, hemoglobin E variants and α(3.7)-thalassemia). Of the 420 nonpregnant women, 29.5% had anemia (hemoglobin 8.3 mg/L), hemoglobin disorders, respectively. There was no biochemical evidence of vitamin A deficiency (RBP 5 mg/L) and 26% (AGP >1 g/L) of nonpregnant women, respectively. By using an adjusted linear regression model, the strongest predictors of hemoglobin concentration were hemoglobin E homozygous disorder and pregnancy status. Other predictors were 2 other heterozygous traits (hemoglobin E and Constant Spring), parity, RBP, log ferritin, and vitamin B-12. Multiple biomarkers for anemia and iron deficiency were significantly influenced by the presence of hemoglobin disorders, hence reducing their diagnostic sensitivity. Further investigation of the unexpectedly low prevalence of IDA in Cambodian women is warranted. © 2015 American Society for Nutrition.

The usage of fasting glucose and glycated hemoglobin for the identification of unknown type 2 diabetes in high risk patients with morbid obesity.

Science.gov (United States)

Valderhaug, Tone G; Sharma, Archana; Kravdal, Gunnhild; Rønningen, Reidun; Nermoen, Ingrid

2017-11-01

In spite of increased vigilance of undiagnosed type 2 diabetes (DM2), the prevalence of unknown DM2 in subjects with morbid obesity is not known. To assess the prevalence of undiagnosed DM2 and compare the performance of glycated A1c (HbA1c) and fasting glucose (FG) for the diagnosis of DM2 and prediabetes (preDM) in patients with morbid obesity. We measured fasting glucose and HbA1c in 537 consecutive patients with morbid obesity without previously known DM2. A total of 49 (9%) patients with morbid obesity had unknown DM2 out of which 16 (33%) fulfilled both the criteria for HbA1c and FG. Out of 284 (53%) subjects with preDM, 133 (47%) fulfilled both the criteria for HbA1c and FG. Measurements of agreement for FG and HbA1c were moderate for DM2 (κ = 0.461, p obesity.

Aspirin-mediated acetylation of haemoglobin increases in presence of high glucose concentration and decreases protein glycation

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Francesco Finamore

2015-09-01

Full Text Available Glycation represents the first stage in the development of diabetic complications. Aspirin was shown to prevent sugars reacting with proteins, but the exact mechanism of this interaction was not well defined. We performed a quantitative analysis to calculate the levels of acetylation and glycation of haemoglobin, among others red blood cell (RBC proteins, using a label free approach. After glucose incubation, increases in the acetylation levels were seen for several haemoglobin subunits, while a parallel decrease of their glycation levels was observed after aspirin incubation. These results suggest that, a mutual influence between these two modifications, occur at protein level.

Evaluation of Structure, Chaperone-Like Activity and Allergenicity of Reduced Glycated Adduct of Bovine β-casein.

Science.gov (United States)

Yousefi, Reza; Ferdowsi, Leila; Tavaf, Zohreh; Sadeghian, Tanaz; Tamaddon, Ali M; Moghtaderi, Mozhgan; Pourpak, Zahra

2017-01-01

Milk has a potent reducing environment with an important quantity of sugar levels. In the current study β-casein was glycated in the presence of D-glucose and sodium cyanoborohydride as a reducing agent. Then, the reduced glucitol adduct of β-casein was used for the structural and functional analyses using different spectroscopic techniques. The results of fluorescence and far ultraviolet circular dichroism assessments suggest important structural alteration upon non-enzymatic glycation of β-casein. In addition, the chaperone activity, micellization properties and antioxidant activity of this protein were altered upon glucose modification. Also, as a result of reduced glycation, the allergenicity profile of this protein remained largely unchanged. Additional to its energetic and nutritional values, β-casein has important functional properties. The native structure of this protein is important to perform accurately its biological functions. Non-enzymatic glycation under reducing state was capable to alter both structural and functional aspects of β-casein. Due to effective reducing environment and significant quantity of reducing sugar of human milk, similar structural and functional alterations are most likely to occur upon reducing glycation of β-casein in vivo. Also, these changes might be even intensified during chronic hyperglycemia in diabetic mothers. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Relationship Between Glycated Haemoglobin and Body Mass Index ...

African Journals Online (AJOL)

Blood pressure, Height, Weight were all measured and body mass index (BMI) calculated as weight (in kilograms) divided by height (in meters squared). Glycated haemoglobin was estimated using the ion exchange chromatography method. Result: A total of 100 healthy subjects, 50 males and 50 females, ages ranging ...

Glycated haemoglobin may in future be reported as estimated mean blood glucose concentration--secondary publication

DEFF Research Database (Denmark)

Borg, R.; Nerup, J.; Nathan, D.M.

2009-01-01

Glycated haemoglobin (HbA 1c ) is widely used to determine levels of chronic glycaemia, to judge the adequacy of diabetes treatment and to adjust therapy. HbA 1c results are expressed as the percentage of HbA that is glycated. Day-to-day management is guided by self-monitoring of capillary glucose...

Glycation in human fingernail clippings using ATR-FTIR spectrometry, a new marker for the diagnosis and monitoring of diabetes mellitus.

Science.gov (United States)

Coopman, Renaat; Van de Vyver, Thijs; Kishabongo, Antoine Sadiki; Katchunga, Philippe; Van Aken, Elisabeth H; Cikomola, Justin; Monteyne, Tinne; Speeckaert, Marijn M; Delanghe, Joris R

2017-01-01

Although HbA1c is a good diagnostic tool for diabetes, the precarity of the health system and the costs limit the use of this biomarker in developing countries. Fingernail clippings contain ±85% of keratins, which are prone to glycation. Nail keratin glycation may reflect the average glycemia over the last months. We explored if attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR) can be used as a non-invasive tool for assessing glycation in diabetes. Using ATR-FTIR spectroscopy, glycation and deglycation experiments with fructosamine 3-kinase allowed to identify the spectrum that corresponds with keratin glycation in fingernail clippings. Clippings of 105 healthy subjects and 127 diabetics were subjected to the standardized ATR-FTIR spectroscopy method. In vitro glycation resulted in an increased absorption at 1047cm -1 . Following enzymatic deglycation, this peak diminished significantly, proving that the AUC between 970 and 1140cm -1 corresponded with glycated proteins. Within-run CV of the assay was 3%. Storage of nail clippings at 37°C for 2weeks did not significantly change results. In diabetics, glycated nail protein concentrations (median: 1.51μmol/g protein, IQR: 1.37-1.85μmol/g protein) were significantly higher than in the controls (median: 1.19μmol/g protein, IQR: 1.09-1.26μmol/g protein) (p<0.0001). ROC analysis yielded an AUC of 0.92 at a cut-off point of 1.28μmol/g nail (specificity: 82%; sensitivity: 90%). No correlation was observed between the glycated nail protein concentrations and HbA1c. Protein glycation analysis in fingernails with ATR-FTIR spectroscopy could be an alternative affordable technique for diagnosing and monitoring diabetes. As the test does not consume reagents, and the preanalytical phase is extremely robust, the test could be particularly useful in developing countries. Copyright © 2016 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Association between Fluorescent Advanced Glycation End-Products and Vascular Complications in Type 2 Diabetic Patients

Directory of Open Access Journals (Sweden)

Alexis Guerin-Dubourg

2017-01-01

Full Text Available Objectives. Diabetes is a major health problem associated with hyperglycemia and chronically increased oxidative stress and enhanced formation of advanced glycation end-products (AGEs. The aim of this study was to determine whether oxidative plasma biomarkers in diabetic patients could be evidenced and associated with vascular complications. Methods. Oxidative stress biomarkers such as thiols, ischemia-modified albumin (IMA, glycated albumin (GA, fructosamine, and AGEs were measured in 75 patients with poorly controlled type 2 diabetes (HbA1c > 7.5% with (44 or without (31 vascular disease and in 31 nondiabetic controls. Results. Most biomarkers of oxidation and glycation were significantly increased in diabetic patients in comparison with nondiabetics. Fructosamines, GA, IMA, and AGEs were positively correlated and levels of fluorescent AGEs were significantly increased in the plasma from patients presenting vascular complication. Conclusions. These results bring new evidence for the potential interest of glycated albumin, oxidative stress, and glycoxidation parameters in the monitoring of type 2 diabetic patients. Furthermore, it emphasizes fluorescent AGEs as a putative indicator for vascular event prediction in diabetic patients.

Postoperative hemoglobin level in patients with femoral neck fracture.

Science.gov (United States)

Nagra, Navraj S; Van Popta, Dmitri; Whiteside, Sigrid; Holt, Edward M

2016-01-01

The aim of this study was to analyze the changes of hemoglobin levels in patients undergoing fixation for femoral neck fracture. Peroperative hemoglobin levels of patients who underwent either dynamic hip screw (DHS) fixation (n=74; mean age: 80 years) or hip hemiarthroplasty (n=104; mean age: 84 years) for femoral neck fracture was monitored. There was a statistically and clinically significant mean drop of 31.1 g/L between the preoperative (D0) and postoperative Day 5 Hb levels (pmeasurement, DHS patients had lower hemoglobin values over hemiarthroplasty patients (p=0.046). The decrease in hemoglobin in the first 24-hour postoperative period (D0 to Day 1) is an underestimation of the ultimate lowest value in hemoglobin found at Day 2. Relying on the Day 1 hemoglobin level could be detrimental to patient care. We propose a method of predicting patients likely to be transfused and recommend a protocol for patients undergoing femoral neck fracture surgery to standardize postoperative hemoglobin monitoring.

Skin advanced glycation end products in HIV infection are increased and predictive of development of cardiovascular events

NARCIS (Netherlands)

Sprenger, Herman G.; Bierman, Wouter F.; Martes, Melanie I.; Graaff, Reindert; van der Werf, Tjip S.; Smit, Andries J.

2017-01-01

Objective: HIV-1 infection is associated with an increased cardiovascular disease (CVD) risk. Advanced glycation end products are formed as stable markers of glycaemic and oxidative stress. Skin autofluorescence (SAF) as marker of accumulated advanced glycation end products is increased and

Diagnostics of impaired carbon metabolism in patients with ischemic heart disease.

Directory of Open Access Journals (Sweden)

G. B. Mankovsky

2018-06-01

Full Text Available Aim of the study – to investigate the prevalence of earlier non-diagnosed type 2 diabetes mellitus and prediabetes using different diagnostic approaches in patients with angiographically confirmed ischemic heart disease. Materials and methods. We studied 89 patients with ischemic heart disease, mean age 62+3,6 years. All patients had angiographically confirmed atherosclerotic lesions of coronary arteries. No patient had previously diagnosed diabetes mellitus or hyperglycemia in anamnesis. All patients underwent the detailed examination to reveal hidden diabetes or prediabetes, earlier non-diagnosed: glucose tolerance, fasting plasma glucose, glycated hemoglobin were measured and standard oral glucose tolerance test was performed. Results. Based on the results of fasting plasma glucose and oral glucose tolerance test, diabetes mellitus was diagnosed in 14 (16% patients studied, elevated glycated hemoglobin suggesting the presence of earlier non-diagnosed diabetes was found in 11 (12% patients. Each of the 3 diagnostic approaches used allowed to diagnose patients with non-diagnosed earlier type 2 diabetes mellitus and there were no statistically significant differences in the prevalence of earlier non-diagnosed diabetes depending on the method of diagnostics used, p>0.05. Prediabetes was diagnosed much more frequently – in 47 (53% patients while measuring glycated hemoglobin, in 43 (48% patients based on fasting plasma glucose levels and in 28 (31% patients according to elevated plasma glucose levels 2 hours after taking glucose. Conclusions. Our data revealed high prevalence of earlier non-diagnosed type 2 diabetes mellitus and prediabetes in patients with ischemic heart disease. The measurement of fasting plasma glucose, glycated hemoglobin and oral glucose tolerance test contribute each other in diagnostics of diabetes and prediabetes in the majority of cases.

Prediction of post translational modifications in avicennia marina Cu-Zn superoxide dismutase: implication of glycation on the enzyme structure

International Nuclear Information System (INIS)

Jabeen, U.; Salim, A.; Abbasi, A.

2012-01-01

3D homology model of Cu-Zn superoxide dismutase (SOD) from Avicennia marina (AMSOD) was constructed using the structural coordinates of Spinach SOD (SSOD). Prediction of post translational modification was done by PROSITE. The predicted sites were examined in the 3D model. AMSOD model was glycated using modeling software and changes in the structure was analyzed after glycation. The analysis revealed some potential sites and structural changes after glycation. (author)

Glycation, oxidation and glycoxidation of IgG: a biophysical, biochemical, immunological and hematological study.

Science.gov (United States)

Islam, Sidra; Moinuddin; Mir, Abdul Rouf; Raghav, Alok; Habib, Safia; Alam, Khursheed; Ali, Asif

2017-09-12

Glycation and oxidation induce structural alterations in the proteins in an interdependent manner with consequent pathological implications. The published literature presents wide range of modifications in conformational characteristics of proteins by glycation and oxidation; however, there is little data that could elaborate the cumulative effect of both the processes. This study has analysed the modifications in IgG by methylglyoxal (MG) (glycative stress), hydroxyl radical ([Formula: see text]) (oxidative stress) and by their combined action i.e. [Formula: see text] treatment of MG glycated IgG (glycoxidation). It further addresses the implications of the altered structural integrity of IgG on its immunological characteristics and impact on haematological parameters in rabbits. Using circular dichroism, FTIR, SDS-PAGE analysis, thioflavin-T fluorescence assay, congo red absorbance analysis, dynamic light scattering, transmission electron microscopy, ELISA, blood cell counts and rectal temperature studies, we report that the glycoxidative modification caused maximum alteration in the IgG as compared to the glycatively and oxidatively modified protein. Far-UV CD results confirmed the highest decline in the beta-pleated sheet content of the protein by glycoxidation. The damage led to the reduced flexibility and enhanced electronic interactions in IgG as observed by near-UV CD. Modifications caused cross-linking and adduct formation in the serum protein. The electron micrograph confirmed amorphous aggregation in modified IgG. The modifications increased the hydrodynamic radius of IgG by allowing the attachment of [Formula: see text] and MG residues. The glycoxidatively modified IgG induced the maximum antibody titres that showed high specificity towards the altered IgG. The glycoxidation of IgG leads to activation of inflammatory pathways.

A high throughput screening assay for identifying glycation inhibitors on MALDI-TOF target.

Science.gov (United States)

Zhang, Qiuting; Tu, Zongcai; Wang, Hui; Fan, Liangliang; Huang, Xiaoqin; Xiao, Hui

2015-03-01

The Maillard reaction plays an important role in the food industry, however, the deleterious effects generated by the advanced glycation end-products (AGEs) have been well recognized. Many efforts have been made to seek new AGE inhibitors, in particular those natural ones without adverse effect. We have developed a rapid, mass spectrometry based, on-plate screening assay for novel AGE inhibitors. The glycation reaction, inhibition feedback as well as the subsequent MALDI mass spectrometric analysis occurred on one single MALDI plate. At 1:10 M ratio of peptide to sugar, as little as 4h incubation time allowed the screening test to be ready for analysis. DSP, inhibition and IC50 were calculated to evaluate selected inhibitors and resulting inhibition efficiencies were consistent with available references. We demonstrated that this method provide a potential high throughput screening assay to analyze and identify the anti-glycation agents. Copyright © 2014 Elsevier Ltd. All rights reserved.

Effect of Maillard induced glycation on protein hydrolysis by lysine/arginine and non-lysine/arginine specific proteases

NARCIS (Netherlands)

Deng, Y.; Wierenga, P.A.; Schols, H.A.; Sforza, S.; Gruppen, H.

2017-01-01

Enzymatic protein hydrolysis is sensitive to modifications of protein structure, e.g. Maillard reaction. In early stages of the reaction glycation takes place, modifying the protein primary structure. In later stages protein aggregation occurs. The specific effect of glycation on protein

Hemoglobin levels in normal Filipino pregnant women.

Science.gov (United States)

Kuizon, M D; Natera, M G; Ancheta, L P; Platon, T P; Reyes, G D; Macapinlac, M P

1981-09-01

The hemoglobin concentrations during pregnancy in Filipinos belonging to the upper income group, who were prescribed 105 mg elemental iron daily, and who had acceptable levels of transferrin saturation, were examined in an attempt to define normal levels. The hemoglobin concentrations for each trimester followed a Gaussian distribution. The hemoglobin values equal to the mean minus one standard deviation were 11.4 gm/dl for the first trimester and 10.4 gm/dl for the second and third trimesters. Using these values as the lower limits of normal, in one group of pregnant women the prevalence of anemia during the last two trimesters was found lower than that obtained when WHO levels for normal were used. Groups of women with hemoglobin of 10.4 to 10.9 gm/dl (classified anemic by WHO criteria but normal in the present study) and those with 11.0 gm/dl and above could not be distinguished on the basis of their serum ferritin levels nor on the degree of decrease in their hemoglobin concentration during pregnancy. Many subjects in both groups, however, had serum ferritin levels less than 12 ng/ml which indicate poor iron stores. It might be desirable in future studies to determine the hemoglobin cut-off point that will delineate subjects who are both non-anemic and adequate in iron stores using serum ferritin levels as criterion for the latter.

Modifications of hemoglobin and myoglobin by Maillard reaction products (MRPs).

Science.gov (United States)

Ioannou, Aristos; Varotsis, Constantinos

2017-01-01

High performance liquid chromatography (HPLC) coupled with a Fraction Collector was employed to isolate Maillard reaction products (MRPs) formed in model systems comprising of asparagine and monosaccharides in the 60-180°C range. The primary MRP which is detected at 60°C is important for Acrylamide content and color/aroma development in foods and also in the field of food biotechnology for controlling the extent of the Maillard reaction with temperature. The discrete fractions of the reaction products were reacted with Hemoglobin (Hb) and Myoglobin (Mb) at physiological conditions and the reaction adducts were monitored by UV-vis and Attenuated Total Reflection-Fourier transform infrared (FTIR) spectrophotometry. The UV-vis kinetic profiles revealed the formation of a Soret transition characteristic of a low-spin six-coordinated species and the ATR-FTIR spectrum of the Hb-MRP and Mb-MRP fractions showed modifications in the protein Amide I and II vibrations. The UV-vis and the FTIR spectra of the Hb-MRPs indicate that the six-coordinated species is a hemichrome in which the distal E7 Histidine is coordinated to the heme Fe and blocks irreversibly the ligand binding site. Although the Mb-MRPs complex is a six-coordinated species, the 1608 cm-1 FTIR band characteristic of a hemichrome was not observed.

Glyoxalase I reduces glycative and oxidative stress and prevents age-related endothelial dysfunction through modulation of endothelial nitric oxide synthase phosphorylation.

Science.gov (United States)

Jo-Watanabe, Airi; Ohse, Takamoto; Nishimatsu, Hiroaki; Takahashi, Masao; Ikeda, Yoichiro; Wada, Takehiko; Shirakawa, Jun-ichi; Nagai, Ryoji; Miyata, Toshio; Nagano, Tetsuo; Hirata, Yasunobu; Inagi, Reiko; Nangaku, Masaomi

2014-06-01

Endothelial dysfunction is a major contributor to cardiovascular disease (CVD), particularly in elderly people. Studies have demonstrated the role of glycation in endothelial dysfunction in nonphysiological models, but the physiological role of glycation in age-related endothelial dysfunction has been poorly addressed. Here, to investigate how vascular glycation affects age-related endothelial function, we employed rats systemically overexpressing glyoxalase I (GLO1), which detoxifies methylglyoxal (MG), a representative precursor of glycation. Four groups of rats were examined, namely young (13 weeks old), mid-age (53 weeks old) wild-type, and GLO1 transgenic (WT/GLO1 Tg) rats. Age-related acceleration in glycation was attenuated in GLO1 Tg rats, together with lower aortic carboxymethyllysine (CML) and urinary 8-hydroxydeoxyguanosine (8-OHdG) levels. Age-related impairment of endothelium-dependent vasorelaxation was attenuated in GLO1 Tg rats, whereas endothelium-independent vasorelaxation was not different between WT and GLO1 Tg rats. Nitric oxide (NO) production was decreased in mid-age WT rats, but not in mid-age GLO1 Tg rats. Age-related inactivation of endothelial NO synthase (eNOS) due to phosphorylation of eNOS on Thr495 and dephosphorylation on Ser1177 was ameliorated in GLO1 Tg rats. In vitro, MG increased phosphorylation of eNOS (Thr495) in primary human aortic endothelial cells (HAECs), and overexpression of GLO1 decreased glycative stress and phosphorylation of eNOS (Thr495). Together, GLO1 reduced age-related endothelial glycative and oxidative stress, altered phohphorylation of eNOS, and attenuated endothelial dysfunction. As a molecular mechanism, GLO1 lessened inhibitory phosphorylation of eNOS (Thr495) by reducing glycative stress. Our study demonstrates that blunting glycative stress prevents the long-term impact of endothelial dysfunction on vascular aging. © 2014 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons

Combined effect of glycation and sodium carbonate-bicarbonate buffer concentration on IgG binding, IgE binding and conformation of ovalbumin.

Science.gov (United States)

Ma, Xiao-juan; Gao, Jin-yan; Chen, Hong-bing

2013-10-01

Ovalbumin (OVA) is a major allergen in hen egg. During thermal processing, reducing sugars contained in the hen egg white might easily undergo glycation with OVA, but few studies have been conducted on its corresponding immunoreactivity changes. The aim of the present study was to assess changes of the antigenicity, potential allergenicity and conformation of OVA after glycation in a wet-thermal processing system under different concentrations of sodium carbonate-bicarbonate buffer. IgE binding of the glycated OVA was increased after glycation, and the higher the sodium carbonate-bicarbonate buffer concentration, the higher the IgE binding capacity. The increase in IgE binding of OVA corresponded well with the disruption of the disulfide bond, which exposed the epitopes initially buried. Antigenicity of the glycated OVA was increased, and the amount of the increase varied among samples treated under different buffer concentrations. Glycation increased the allergenic potential for OVA, with the amount of increase varying with different sodium carbonate-bicarbonate buffer concentrations. © 2013 Society of Chemical Industry.

Individualized anemia management reduces hemoglobin variability in hemodialysis patients.

Science.gov (United States)

Gaweda, Adam E; Aronoff, George R; Jacobs, Alfred A; Rai, Shesh N; Brier, Michael E

2014-01-01

One-size-fits-all protocol-based approaches to anemia management with erythropoiesis-stimulating agents (ESAs) may result in undesired patterns of hemoglobin variability. In this single-center, double-blind, randomized controlled trial, we tested the hypothesis that individualized dosing of ESA improves hemoglobin variability over a standard population-based approach. We enrolled 62 hemodialysis patients and followed them over a 12-month period. Patients were randomly assigned to receive ESA doses guided by the Smart Anemia Manager algorithm (treatment) or by a standard protocol (control). Dose recommendations, performed on a monthly basis, were validated by an expert physician anemia manager. The primary outcome was the percentage of hemoglobin concentrations between 10 and 12 g/dl over the follow-up period. A total of 258 of 356 (72.5%) hemoglobin concentrations were between 10 and 12 g/dl in the treatment group, compared with 208 of 336 (61.9%) in the control group; 42 (11.8%) hemoglobin concentrations were hemoglobin concentrations were >12 g/dl in the treatment group compared with 46 (13.4%) in the control group. The median ESA dosage per patient was 2000 IU/wk in both groups. Five participants received 6 transfusions (21 U) in the treatment group, compared with 8 participants and 13 transfusions (31 U) in the control group. These results suggest that individualized ESA dosing decreases total hemoglobin variability compared with a population protocol-based approach. As hemoglobin levels are declining in hemodialysis patients, decreasing hemoglobin variability may help reduce the risk of transfusions in this population.

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

Science.gov (United States)

Booth, Ronald A; Jiang, Ying; Morrison, Howard; Orpana, Heather; Rogers Van Katwyk, Susan; Lemieux, Chantal

2018-02-01

Previous studies have shown varying sensitivity and specificity of hemoglobin A1c (HbA1c) to identify diabetes and prediabetes, compared to 2-h oral glucose tolerance testing (OGTT) and fasting plasma glucose (FPG), in different ethnic groups. Within the Canadian population, the ability of HbA1c to identify prediabetes and diabetes in First Nations, Métis and Inuit, East and South Asian ethnic groups has yet to be determined. We collected demographic, lifestyle information, biochemical results of glycemic status (FPG, OGTT, and HbA1c) from an ethnically diverse Canadian population sample, which included a purposeful sampling of First Nations, Métis, Inuit, South Asian and East Asian participants. Sensitivity and specificity using Canadian Diabetes Association (CDA) recommended cut-points varied between ethnic groups, with greater variability for identification of prediabetes than diabetes. Dysglycemia (prediabetes and diabetes) was identified with a sensitivity and specificity ranging from 47.1% to 87.5%, respectively in Caucasians to 24.1% and 88.8% in Inuit. Optimal HbA1c ethnic-specific cut-points for dysglycemia and diabetes were determined by receiver operating characteristic (ROC) curve analysis. Our sample showed broad differences in the ability of HbA1c to identify dysglycemia or diabetes in different ethnic groups. Optimal cut-points for dysglycemia or diabetes in all ethnic groups were substantially lower than CDA recommendations. Utilization of HbA1c as the sole biochemical diagnostic marker may produce varying degrees of false negative results depending on the ethnicity of screened individuals. Further research is necessary to identify and validate optimal ethnic specific cut-points used for diabetic screening in the Canadian population. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

Antioxidative capacity and binding affinity of the complex of green tea catechin and beta-lactoglobulin glycated by the Maillard reaction.

Science.gov (United States)

Perusko, Marija; Al-Hanish, Ayah; Mihailovic, Jelena; Minic, Simeon; Trifunovic, Sara; Prodic, Ivana; Cirkovic Velickovic, Tanja

2017-10-01

Major green tea catechin, epigallocatechin-3-gallate (EGCG), binds non-covalently to numerous dietary proteins, including beta-lactoglobulin of cow's milk. The effects of glycation of proteins via Maillard reaction on the binding capacity for polyphenols and the antiradical properties of the formed complexes have not been studied previously. Binding constant of BLG glycated by milk sugar lactose to EGCG was measured by the method of fluorophore quenching. Binding of EGCG was confirmed by CD and FTIR. The antioxidative properties of the complexes were examined by measuring ABTS radical scavenging capacity, superoxide anion scavenging capacity and total reducing power assay. Glycation of BLG does not significantly influence the binding constant of EGCG for the protein. Conformational changes were observed for both native and glycated BLG upon complexation with EGCG. Masking effect of polyphenol complexation on the antioxidative potential of the protein was of the similar degree for both glycated BLG and native BLG. Copyright © 2017 Elsevier Ltd. All rights reserved.

The interaction of 2,3-diphosphoglycerate with various human hemoglobins

Science.gov (United States)

Bunn, H. Franklin; Briehl, Robin W.

1970-01-01

Oxygen equilibria were measured on a number of human hemoglobins, which had been “stripped” of organic phosphates and isolated by column chromatography. In the presence of 2 × 10-4 M 2,3-diphosphoglycerate (2,3-DPG), the P50 of hemoglobins A, A2, S, and C increased about twofold, signifying a substantial and equal decrease in oxygen affinity. Furthermore, hemoglobins Chesapeake and MMilwaukee-1 which have intrinsically high and low oxygen affinities, respectively, also showed a twofold increase in P50 in the presence of 2 × 10-4 M 2,3-DPG. In comparison to these, hemoglobins AIC and F were less reactive with 2,3-DPG while hemoglobin FI showed virtually no reactivity. The N-terminal amino of each β-chain of hemoglobin AIC is linked to a hexose. In hemoglobin FI the N-terminal amino of each γ-chain is acetylated. These results suggest that the N-terminal amino groups of the non-α-chains are involved in the binding of 2,3-DPG to hemoglobin. PMID:5422014

Porphyromonas endodontalis binds, reduces and grows on human hemoglobin.

Science.gov (United States)

Zerr, M; Drake, D; Johnson, W; Cox, C D

2001-08-01

Porphyromonas endodontalis is a black-pigmented, obligate anaerobic rod-shaped bacterium implicated as playing a major role in endodontic infections. We have previously shown that P. endodontalis requires the porphyrin nucleus, preferably supplied as hemoglobin, as a growth supplement. The bacteria also actively transport free iron, although this activity does not support growth in the absence of a porphyrin source. The purpose of this study was to further investigate the binding and subsequent utilization of human hemoglobin by P. endodontalis. P. endodontalis binds hemoglobin and reduces the Fe(III) porphyrin, resulting in a steady accumulation of ferrous hemoglobin. Reduction of methemoglobin was similar to the extracellular reduction of nitrobluetetrazolium in the presence of oxidizable substrate. Turbidimetric and viable cell determinations showed that P. endodontalis grew when supplied only hemoglobin. Therefore, we conclude that hemoglobin appears to serve as a sole carbon and nitrogen source, and that these bacteria reduce extracellular compounds at the expense of oxidized substrates.

Post-transfusion hemoglobin values and patient blood management

DEFF Research Database (Denmark)

Moerman, Jan; Vermeulen, Edith; Van Mullem, Mia

2018-01-01

Objectives: The objective of this retrospective study was to evaluate the added value of communicating post-transfusion hemoglobin values to clinicians as a strategy to improve RBC utilization in a 500-bed hospital. Methods: The total number of RBC transfusions, the mean number of RBC units...... transfused per patient, the mean pre- and post-transfusion hemoglobin values, the ratio of patients transfused and the ratio of patients with a post-transfusion hemoglobin > 10.5 g/dL were calculated per service and per department for six months. The data were reported to each service and compared...... with the data of the department as peer group. The impact of this communication strategy was evaluated in the following six months. Results: In the six months pre-intervention, the mean post-transfusion hemoglobin value was 9.2 g/dL. Post-transfusion hemoglobin was > 10.5 g/dL in 13.4% of patients (112...

Hemoglobin affinity in Andean rodents

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HRVOJ OSTOJIC

2002-01-01

Full Text Available Blood hemoglobin oxygen affinity (P50 was measured in three Andean species and in the laboratory rat (control, all raised near sea level. Chinchilla lanigera (Molina, 1792 has an altitudinal habitat range from low Andean slopes up to 3000 m., while Chinchilla brevicaudata (Waterhouse, 1848 has an altitudinal range from 3000 to 5000 m. The laboratory type guinea pig, wild type guinea pig (Cavia porcellus, (Waterhouse, 1748, and laboratory rat (Rattus norvegicus were also raised at sea level. The Andean species had high hemoglobin oxygen affinities (low P50 compared with the rat. Chinchilla brevicaudata had a higher affinity than Chinchilla lanigera. The wild type guinea pig had a higher affinity than the laboratory type. As has been shown in other species, this is another example of an inverse correlation between the altitude level and the P50 values. This is the first hemoglobin oxygen affinity study in Chinchilla brevicaudata.

Covalent glycoinositolphospholipid (GPI binding to hemoglobin is associated with insulin-activation of erythrocyte membrane protease

Directory of Open Access Journals (Sweden)

VESNA NIKETIC

2004-05-01

Full Text Available Recently, it was demonstrated that prolonged hyperinsulinism associated with hypoglycemia, both in vivo and in vitro, caused covalent glycoinositolphospholipid (GPI binding to the C termini of both hemoglobin b-chains, which resulted in the formation of a novel, hitherto unrecognized, minor hemoglobin fraction (GPI-Hb (Niketic et al., Biochem. Biophys. Res. Commun. 239 (1997 435. In this study it was demonstrated that exposure of erythrocyte membranes to insulin causes the activation of membrane protease as well as that the formation of GPI-Hb parallels its activity. It is suggested that the insulin-activated protease is able to catalyze, albeit slowly, the transpeptidation, i.e., the replacement of the carboxy-terminal amino acid(s residues of the Hb b-chains with GPI as an exogenous nucleophile. To our knowledge the present results show for the first time that insulin stimulates protease activity in erythrocyte membranes, as well as that insulin-activated protease may be involved in post-translational GPI binding to proteins.

In Vitro Inhibitory Activity of Acca sellowiana Fruit Extract on End Products of Advanced Glycation.

Science.gov (United States)

Muñiz, Alethia; Garcia, Abraham H; Pérez, Rosa M; García, Efren V; González, Daphne E

2018-02-01

Hyperglycemia plays an important role in the pathogenesis of diabetic complications, as it increases protein glycation, as well as the progressive accumulation of advanced glycation end products (AGEs), which are complex structures that produce fluorescence. The glycation reaction raises the levels of protein carbonyl, N ε -(carboxymethyl)lysine (CML), and fructosamine and decreases the level of thiol groups. In the present study, the antiglycation activity was determined by fluorescence intensity using the bovine serum albumin (BSA)/glucose, CML method, and the level of fructosamine. The oxidation of proteins was determined by the carbonyl protein content and thiol groups. The results show that the hexane extract of Acca sellowiana (FOH) at different concentrations (0.30-5 mg/ml) significantly inhibited the formation of AGEs in the BSA/glucose model during the 4 weeks of the study. FOH reduced the levels of fructosamine and CML. Our results showed a significant effect of FOH in the prevention of oxidative damage of proteins, as well as an effect on the oxidation of thiol groups and carbonyl proteins. The present study indicates that FOH is effective in inhibiting the glycation of proteins in vitro, so it can prevent or ameliorate the chronic conditions of diabetes associated with the formation of AGEs.

Advanced glycation end products and RAGE: a common thread in aging, diabetes, neurodegeneration, and inflammation.

Science.gov (United States)

Ramasamy, Ravichandran; Vannucci, Susan J; Yan, Shirley Shi Du; Herold, Kevan; Yan, Shi Fang; Schmidt, Ann Marie

2005-07-01

The products of nonenzymatic glycation and oxidation of proteins and lipids, the advanced glycation end products (AGEs), accumulate in a wide variety of environments. AGEs may be generated rapidly or over long times stimulated by a range of distinct triggering mechanisms, thereby accounting for their roles in multiple settings and disease states. A critical property of AGEs is their ability to activate receptor for advanced glycation end products (RAGE), a signal transduction receptor of the immunoglobulin superfamily. It is our hypothesis that due to such interaction, AGEs impart a potent impact in tissues, stimulating processes linked to inflammation and its consequences. We hypothesize that AGEs cause perturbation in a diverse group of diseases, such as diabetes, inflammation, neurodegeneration, and aging. Thus, we propose that targeting this pathway may represent a logical step in the prevention/treatment of the sequelae of these disorders.

Insulin resistance is associated with carotid intima-media thickness in non-diabetic subjects. A cross-sectional analysis of the ELSA-Brasil cohort baseline.

Science.gov (United States)

Santos, Itamar S; Bittencourt, Márcio S; Goulart, Alessandra C; Schmidt, Maria Inês; Diniz, Maria de Fátima H S; Lotufo, Paulo A; Benseñor, Isabela M

2017-05-01

Epidemiological studies have analyzed the association between carotid intima-media thickness (CIMT) and insulin resistance, glucose levels or glycated hemoglobin with mixed results. We aimed to evaluate the association between CIMT and homeostasis model assessment - insulin resistance (HOMA-IR), fasting and post-load plasma glucose and glycated hemoglobin in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) baseline. We included 8028 participants (aged 35-74 years) without diabetes or overt cardiovascular disease who had complete CIMT data at baseline. We built crude and adjusted linear and binary logistic models to evaluate the association between CIMT and (a) HOMA-IR; (b) fasting plasma glucose; (c) post-load plasma glucose; and (d) glycated hemoglobin. We also built post-hoc models, stratified by sex. In the fully-adjusted linear models, only the association between CIMT (in mm) and HOMA-IR remained significant (β = 0.004; 95% confidence interval [95%CI]:0.001 to 0.006). Consistent with these results, only the association between the highest age- sex- and race-specific CIMT quartile and HOMA-IR was significant in the adjusted logistic model (odds ratio [OR]:1.10; 95% CI:1.04-1.17). The association between HOMA-IR and the highest CIMT quartile remained significant in sex-specific analyses (OR:1.10; 95% CI:1.02-1.20 for men and OR:1.10; 95% CI:1.02-1.20 for women). We did not find an independent association between CIMT and glucose or glycated hemoglobin. We found a direct association between HOMA-IR and CIMT in a large sample of non-diabetic participants. Mechanisms unrelated to glucose homeostasis, as a direct effect of insulin on atherosclerosis, or medial hypertrophy, may be involved. Copyright © 2017 Elsevier B.V. All rights reserved.

Glycemic Control and Urinary Tract Infections in Women with Type 1 Diabetes: Results from the DCCT/EDIC.

Science.gov (United States)

Lenherr, Sara M; Clemens, J Quentin; Braffett, Barbara H; Cleary, Patricia A; Dunn, Rodney L; Hotaling, James M; Jacobson, Alan M; Kim, Catherine; Herman, William; Brown, Jeanette S; Wessells, Hunter; Sarma, Aruna V

2016-10-01

We examined the relationship between glycemic control and urinary tract infections in women with type 1 diabetes mellitus. Women enrolled in the Epidemiology of Diabetes Interventions and Complications study, the observational followup of the Diabetes Control and Complications Trial, were surveyed to assess the rate of physician diagnosed urinary tract infections in the preceding 12 months. The relationship between glycated hemoglobin levels and number of urinary tract infections in the previous 12 months was assessed using a multivariable Poisson regression model. A total of 572 women were evaluated at year 17. Mean age was 50.7 ± 7.2 years, mean body mass index was 28.6 ± 5.9 kg/m(2), mean type 1 diabetes duration was 29.8 ± 5.0 years and mean glycated hemoglobin was 8.0% ± 0.9%. Of these women 86 (15.0%) reported at least 1 physician diagnosed urinary tract infection during the last 12 months. Higher glycated hemoglobin levels were significantly associated with number of urinary tract infections such that for every unit increase (1%) in recent glycated hemoglobin level, there was a 21% (p=0.02) increase in urinary tract infection frequency in the previous 12 months after adjusting for race, hysterectomy status, urinary incontinence, sexual activity in the last 12 months, peripheral and autonomic neuropathy, and nephropathy. The frequency of urinary tract infections increases with poor glycemic control in women with type 1 diabetes. This relationship is independent of other well described predictors of urinary tract infections and suggests that factors directly related to glycemic control may influence the risk of lower urinary tract infections. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Fucoidan as an inhibitor of thermally induced collagen glycation examined by acetate electrophoresis.

Science.gov (United States)

Pielesz, Anna; Paluch, Jadwiga

2014-08-01

Non-enzymatic glycation (Maillard reaction) in vitro could be a simple method to obtain glycoconjugates for studying their biological properties. Hence, fucoidan was retained by acetate electrophoresis indicating a strong interaction with the protein. A loss of colour in fucoidan bands was found for samples incubated with collagen as compared with samples of free fucoidan. Also under in vitro conditions at 100°C - simulating a sudden burn incident - fucoidan binds with collagen as a result of the Maillard reaction. In contrast, the colour of the fucoidan bands intensified for samples incubated with collagen, with the addition of glucose. Electrophoretic analyses were carried out after heating the samples to a temperature simulating a burn incident. The bands were found to intensify for samples incubated with collagen during a 30-day-long incubation. Thus, spontaneous in vitro glycation - i.e. without the addition of glucose - was confirmed. This process is highly intensified both by the temperature and time of incubation. For a sample incubated in vitro in a fucoidan solution containing glucose, glycation was confirmed in a preliminary FTIR and acetate electrophoresis examinations, occurring in collagen obtained from chicken skins. In particular, a new band emerging around 1746 cm(-1) was observed for above samples, as was its increasing intensity, as compared with samples without the addition of glucose. In the collagen glycation assay, while glucose reacts with collagen and forms cross-linked aggregates, fucoidan decreases the process of aggregation and recovery of native collagen. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Crystallographic analysis of human hemoglobin elucidates the structural basis of the potent and dual antisickling activity of pyridyl derivatives of vanillin

Energy Technology Data Exchange (ETDEWEB)

Abdulmalik, Osheiza [The Children’s Hospital of Philadelphia, Philadelphia, PA 19104 (United States); Ghatge, Mohini S.; Musayev, Faik N.; Parikh, Apurvasena [Virginia Commonwealth University, Richmond, VA 23298 (United States); Chen, Qiukan; Yang, Jisheng [The Children’s Hospital of Philadelphia, Philadelphia, PA 19104 (United States); Nnamani, Ijeoma [Duke University Medical Center, Durham, NC 27710 (United States); Danso-Danquah, Richmond [Virginia Commonwealth University, Richmond, VA 23298 (United States); Eseonu, Dorothy N. [Virginia Union University, Richmond, VA 23220 (United States); Asakura, Toshio [Duke University Medical Center, Durham, NC 27710 (United States); Abraham, Donald J.; Venitz, Jurgen; Safo, Martin K., E-mail: msafo@vcu.edu [Virginia Commonwealth University, Richmond, VA 23298 (United States); The Children’s Hospital of Philadelphia, Philadelphia, PA 19104 (United States)

2011-11-01

Pyridyl derivatives of vanillin increase the fraction of the more soluble oxygenated sickle hemoglobin and/or directly increase the solubility of deoxygenated sickle hemoglobin. Crystallographic analysis reveals the structural basis of the potent and dual antisickling activity of these derivatives. Vanillin has previously been studied clinically as an antisickling agent to treat sickle-cell disease. In vitro investigations with pyridyl derivatives of vanillin, including INN-312 and INN-298, showed as much as a 90-fold increase in antisickling activity compared with vanillin. The compounds preferentially bind to and modify sickle hemoglobin (Hb S) to increase the affinity of Hb for oxygen. INN-312 also led to a considerable increase in the solubility of deoxygenated Hb S under completely deoxygenated conditions. Crystallographic studies of normal human Hb with INN-312 and INN-298 showed that the compounds form Schiff-base adducts with the N-terminus of the α-subunits to constrain the liganded (or relaxed-state) Hb conformation relative to the unliganded (or tense-state) Hb conformation. Interestingly, while INN-298 binds and directs its meta-positioned pyridine-methoxy moiety (relative to the aldehyde moiety) further down the central water cavity of the protein, that of INN-312, which is ortho to the aldehyde, extends towards the surface of the protein. These studies suggest that these compounds may act to prevent sickling of SS cells by increasing the fraction of the soluble high-affinity Hb S and/or by stereospecific inhibition of deoxygenated Hb S polymerization.

Crystallographic analysis of human hemoglobin elucidates the structural basis of the potent and dual antisickling activity of pyridyl derivatives of vanillin

International Nuclear Information System (INIS)

Abdulmalik, Osheiza; Ghatge, Mohini S.; Musayev, Faik N.; Parikh, Apurvasena; Chen, Qiukan; Yang, Jisheng; Nnamani, Ijeoma; Danso-Danquah, Richmond; Eseonu, Dorothy N.; Asakura, Toshio; Abraham, Donald J.; Venitz, Jurgen; Safo, Martin K.

2011-01-01

Pyridyl derivatives of vanillin increase the fraction of the more soluble oxygenated sickle hemoglobin and/or directly increase the solubility of deoxygenated sickle hemoglobin. Crystallographic analysis reveals the structural basis of the potent and dual antisickling activity of these derivatives. Vanillin has previously been studied clinically as an antisickling agent to treat sickle-cell disease. In vitro investigations with pyridyl derivatives of vanillin, including INN-312 and INN-298, showed as much as a 90-fold increase in antisickling activity compared with vanillin. The compounds preferentially bind to and modify sickle hemoglobin (Hb S) to increase the affinity of Hb for oxygen. INN-312 also led to a considerable increase in the solubility of deoxygenated Hb S under completely deoxygenated conditions. Crystallographic studies of normal human Hb with INN-312 and INN-298 showed that the compounds form Schiff-base adducts with the N-terminus of the α-subunits to constrain the liganded (or relaxed-state) Hb conformation relative to the unliganded (or tense-state) Hb conformation. Interestingly, while INN-298 binds and directs its meta-positioned pyridine-methoxy moiety (relative to the aldehyde moiety) further down the central water cavity of the protein, that of INN-312, which is ortho to the aldehyde, extends towards the surface of the protein. These studies suggest that these compounds may act to prevent sickling of SS cells by increasing the fraction of the soluble high-affinity Hb S and/or by stereospecific inhibition of deoxygenated Hb S polymerization

Open tubular capillary electrochromatography: A useful microreactor for collagen I glycation and interaction studies with low-density lipoprotein particles

International Nuclear Information System (INIS)

D'Ulivo, Lucia; Witos, Joanna; Ooerni, Katariina; Kovanen, Petri T.; Riekkola, Marja-Liisa

2010-01-01

Diabetes, a multifunctional disease and a major cause of morbidity and mortality in the industrialized countries, strongly associates with the development and progression of atherosclerosis. One of the consequences of high level of glucose in the blood circulation is glycation of long-lived proteins, such as collagen I, the most abundant component of the extracellular matrix (ECM) in the arterial wall. Glycation is a long-lasting process that involves the reaction between a carbonyl group of the sugar and an amino group of the protein, usually a lysine residue. This reaction generates an Amadori product that may evolve in advanced glycation end products (AGEs). AGEs, as reactive molecules, can provoke cross-linking of collagen I fibrils. Since binding of low-density lipoproteins (LDLs) to the ECM of the inner layer of the arterial wall, the intima, has been implicated to be involved in the onset of the development of an atherosclerotic plaque, collagen modifications, which can affect the affinity of native and oxidized LDL for collagen I, can promote the entrapment of LDLs in the intima and accelerate the progression of atherosclerosis. In this study, open tubular capillary electrochromatography is proposed as a new microreactor to study in situ glycation of collagen I. The kinetics of glycation was first investigated in a fused silica collagen I-coated capillary. Dimethyl sulphoxide, injected as an electroosmotic flow marker, gave information about the charge of coating. Native and oxidized LDL, and selected peptide fragments from apolipoprotein B-100, the protein covering LDL particles, were injected as marker compounds to clarify the interactions between LDLs and the glycated collagen I coating. The method proposed is simple and inexpensive, since only small amounts of collagen and LDL are required. Atomic force microscopy images complemented our studies, highlighting the difference between unmodified and glycated collagen I surfaces.

Open tubular capillary electrochromatography: A useful microreactor for collagen I glycation and interaction studies with low-density lipoprotein particles

Energy Technology Data Exchange (ETDEWEB)

D' Ulivo, Lucia; Witos, Joanna [Laboratory of Analytical Chemistry, Department of Chemistry, P.O. Box 55, FIN-00014 University of Helsinki (Finland); Ooerni, Katariina; Kovanen, Petri T. [Wihuri Research Institute, Kalliolinnantie 4, FIN-00140, Helsinki (Finland); Riekkola, Marja-Liisa, E-mail: marja-liisa.riekkola@helsinki.fi [Laboratory of Analytical Chemistry, Department of Chemistry, P.O. Box 55, FIN-00014 University of Helsinki (Finland)

2010-04-07

Diabetes, a multifunctional disease and a major cause of morbidity and mortality in the industrialized countries, strongly associates with the development and progression of atherosclerosis. One of the consequences of high level of glucose in the blood circulation is glycation of long-lived proteins, such as collagen I, the most abundant component of the extracellular matrix (ECM) in the arterial wall. Glycation is a long-lasting process that involves the reaction between a carbonyl group of the sugar and an amino group of the protein, usually a lysine residue. This reaction generates an Amadori product that may evolve in advanced glycation end products (AGEs). AGEs, as reactive molecules, can provoke cross-linking of collagen I fibrils. Since binding of low-density lipoproteins (LDLs) to the ECM of the inner layer of the arterial wall, the intima, has been implicated to be involved in the onset of the development of an atherosclerotic plaque, collagen modifications, which can affect the affinity of native and oxidized LDL for collagen I, can promote the entrapment of LDLs in the intima and accelerate the progression of atherosclerosis. In this study, open tubular capillary electrochromatography is proposed as a new microreactor to study in situ glycation of collagen I. The kinetics of glycation was first investigated in a fused silica collagen I-coated capillary. Dimethyl sulphoxide, injected as an electroosmotic flow marker, gave information about the charge of coating. Native and oxidized LDL, and selected peptide fragments from apolipoprotein B-100, the protein covering LDL particles, were injected as marker compounds to clarify the interactions between LDLs and the glycated collagen I coating. The method proposed is simple and inexpensive, since only small amounts of collagen and LDL are required. Atomic force microscopy images complemented our studies, highlighting the difference between unmodified and glycated collagen I surfaces.

Committee on Diabetes Mellitus Indices of the Japan Society of Clinical Chemistry-recommended reference measurement procedure and reference materials for glycated albumin determination.

Science.gov (United States)

Takei, Izumi; Hoshino, Tadao; Tominaga, Makoto; Ishibashi, Midori; Kuwa, Katsuhiko; Umemoto, Masao; Tani, Wataru; Okahashi, Mikiko; Yasukawa, Keiko; Kohzuma, Takuji; Sato, Asako

2016-01-01

Glycated albumin is an intermediate glycaemic control marker for which there are several measurement procedures with entirely different reference intervals. We have developed a reference measurement procedure for the purpose of standardizing glycated albumin measurements. The isotope dilution liquid chromatography/tandem mass spectrometry method was developed as a reference measurement procedure for glycated albumin. The stable isotopes of lysine and fructosyl-lysine, which serve as an internal standard, were added to albumin isolated from serum, followed by hydrogenation. After hydrolysis of albumin with hot hydrochloric acid, the liberated lysine and fructosyl-lysine were measured by liquid chromatography/tandem mass spectrometry, and their concentrations were determined from each isotope ratio. The reference materials (JCCRM611) for determining of glycated albumin were prepared from pooled patient blood samples. The isotope dilution-tandem mass spectrometry calibration curve of fructosyl-lysine and lysine showed good linearity (r = 0.999). The inter-assay and intra-assay coefficient of variation values of glycated albumin measurement were 1.2 and 1.4%, respectively. The glycated albumin values of serum in patients with diabetes assessed through the use of this method showed a good relationship with routine measurement procedures (r = 0.997). The relationship of glycated albumin values of the reference material (JCCRM611) between these two methods was the same as the relationship with the patient serum samples. The Committee on Diabetes Mellitus Indices of the Japan Society of Clinical Chemistry recommends the isotope dilution liquid chromatography/tandem mass spectrometry method as a reference measurement procedure, and JCCRM611 as a certified reference material for glycated albumin measurement. In addition, we recommend the traceability system for glycated albumin measurement. © The Author(s) 2015.

Kadar Hemoglobin dan Kecerdasan Intelektual Anak

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Yuni Kusmiyati

2013-10-01

Full Text Available Kualitas sumber daya manusia dipengaruhi oleh inteligensi anak. Skor kecerdasan intelektual yang tidak menetap pada usia tertentu dapat berubah karena faktor genetik, gizi, dan lingkungan. Tujuan penelitian ini adalah mengetahui hubungan kadar hemoglobin dengan kecerdasan intelektual anak. Penelitian observasional dengan desain potong lintang ini dilakukan pada populasi siswa kelas VI Sekolah Dasar Negeri Giwangan Yogyakarta, tahun 2013. Penarikan sampel dilakukan dengan metode simple random sampling terhadap 37 sampel siswa. Instrumen untuk mengukur kecerdasan intelektual dengan Cultural Fair Intelligence Quotient Test yang dirancang untuk meminimalkan pengaruh kultural dengan memperhatikan prosedur evaluasi, instruksi, konten isi, dan respons peserta. Tes dilakukan oleh Biro Psikologi Universitas Ahmad Dahlan Yogyakarta, kadar hemoglobin diukur menggunakan Portable Hemoglobin Digital Analyzer Easy Touch secara digital.Variabel luar indeks massa tubuh diukur langsung menggunakan parameter tinggi badan dan berat badan. Analisis menggunakan uji regresi linier. Hasil penelitian menunjukkan indeks massa tubuh tidak berhubungan dengan kecerdasan intelektual (nilai p = 0,052. Anemia berhubungan cukup dengan kecerdasan anak (r = 0,491 dan berpola positif, semakin tinggi kadar hemoglobin semakin tinggi kecerdasan intelektual anak. Nilai koefisien determinasi 0,241 menerangkan bahwa 24,1% variasi anemia cukup baik untuk menjelaskan variabel kecerdasan intelektual. Ada hubungan antara kadar hemoglobin dengan kecerdasan intelektual (nilai p = 0,002. Quality of human resources is influenced by the child’s intelligent. Intelligence Quotient (IQ score will not settle at a certain age and can change due to genetic factors, nutrition, and the environment. The objective is known relationship of anemia with IQ to child. Method of observational study with cross sectional design. Population are students of class VI elementary school of Giwangan Yogyakarta in

Receptor targeting of hemoglobin mediated by the haptoglobins

DEFF Research Database (Denmark)

Nielsen, Marianne Jensby; Moestrup, Søren Kragh

2009-01-01

Haptoglobin, the haptoglobin-hemoglobin receptor CD163, and the heme oxygenase-1 are proteins with a well-established function in the clearance and metabolism of "free" hemoglobin released during intravascular hemolysis. This scavenging system counteracts the potentially harmful oxidative and NO......-scavenging effects associated with "free" hemoglobin, and, furthermore, elicits an anti-inflammatory response. In the late primate evolution, haptoglobin variants with distinct functions have arisen, including haptoglobin polymers and the haptoglobin-related protein. The latter associates with a subspecies of high......-density lipoprotein (HDL) particles playing a crucial role in the innate immunity against certain trypanosome parasites. Recent studies have elucidated this fairly sophisticated immune defense mechanism that takes advantage of a trypanosomal haptoglobin-hemoglobin receptor evolved to supply the parasite with heme...

Cell volume regulation in hemoglobin CC and AA erythrocytes

International Nuclear Information System (INIS)

Berkowitz, L.R.; Orringer, E.P.

1987-01-01

Swelling hemoglobin CC erythrocytes stimulates a ouabain-insensitive K flux that restores original cell volume. Studies were performed with the K analog, 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

d-Ribose as a Contributor to Glycated Haemoglobin

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Xixi Chen

2017-11-01

Full Text Available Glycated haemoglobin (HbA1c is the most important marker of hyperglycaemia in diabetes mellitus. We show that d-ribose reacts with haemoglobin, thus yielding HbA1c. Using mass spectrometry, we detected glycation of haemoglobin with d-ribose produces 10 carboxylmethyllysines (CMLs. The first-order rate constant of fructosamine formation for d-ribose was approximately 60 times higher than that for d-glucose at the initial stage. Zucker Diabetic Fatty (ZDF rat, a common model for type 2 diabetes mellitus (T2DM, had high levels of d-ribose and HbA1c, accompanied by a decrease of transketolase (TK in the liver. The administration of benfotiamine, an activator of TK, significantly decreased d-ribose followed by a decline in HbA1c. In clinical investigation, T2DM patients with high HbA1c had a high level of urine d-ribose, though the level of their urine d-glucose was low. That is, d-ribose contributes to HbA1c, which prompts future studies to further explore whether d-ribose plays a role in the pathophysiological mechanism of T2DM.

Hemoglobin and heme scavenger receptors

DEFF Research Database (Denmark)

Nielsen, Marianne Jensby; Møller, Holger Jon; Moestrup, Søren Kragh

2010-01-01

Heme, the functional group of hemoglobin, myoglobin, and other hemoproteins, is a highly toxic substance when it appears in the extracellular milieu. To circumvent potential harmful effects of heme from hemoproteins released during physiological or pathological cell damage (such as hemolysis...... and rhabdomyolysis), specific high capacity scavenging systems have evolved in the mammalian organism. Two major systems, which essentially function in a similar way by means of a circulating latent plasma carrier protein that upon ligand binding is recognized by a receptor, are represented by a) the hemoglobin...

21 CFR 864.7455 - Fetal hemoglobin assay.

Science.gov (United States)

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) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Kits and Packages § 864.7455 Fetal hemoglobin...

Modifications of hemoglobin and myoglobin by Maillard reaction products (MRPs.

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Aristos Ioannou

Full Text Available High performance liquid chromatography (HPLC coupled with a Fraction Collector was employed to isolate Maillard reaction products (MRPs formed in model systems comprising of asparagine and monosaccharides in the 60-180°C range. The primary MRP which is detected at 60°C is important for Acrylamide content and color/aroma development in foods and also in the field of food biotechnology for controlling the extent of the Maillard reaction with temperature. The discrete fractions of the reaction products were reacted with Hemoglobin (Hb and Myoglobin (Mb at physiological conditions and the reaction adducts were monitored by UV-vis and Attenuated Total Reflection-Fourier transform infrared (FTIR spectrophotometry. The UV-vis kinetic profiles revealed the formation of a Soret transition characteristic of a low-spin six-coordinated species and the ATR-FTIR spectrum of the Hb-MRP and Mb-MRP fractions showed modifications in the protein Amide I and II vibrations. The UV-vis and the FTIR spectra of the Hb-MRPs indicate that the six-coordinated species is a hemichrome in which the distal E7 Histidine is coordinated to the heme Fe and blocks irreversibly the ligand binding site. Although the Mb-MRPs complex is a six-coordinated species, the 1608 cm-1 FTIR band characteristic of a hemichrome was not observed.

Fluorescent eosin probe in investigations of structural changes in glycated proteins

Science.gov (United States)

Pravdin, A. B.; Kochubey, V. I.; Mel'Nikov, A. G.

2010-08-01

The possibility of using the luminescent-kinetic probe method to investigate structural changes in bovine serum albumin (BSA) upon nonenzymatic thermal glycation is studied. An increase in the glycation time lead to a decrease in the intensity of the probe (eosin) fluorescence and to a long-wavelength shift of its maximum, as well as to an increase in the eosin phosphorescence intensity, which indicates that eosin binds to hydrophobic regions of protein at any times of incubation of BSA with glucose. From a decrease in the rate constant of the triplet-triplet energy transfer between the donor (eosin) and acceptor (anthracene) bound to proteins, it is found that the changes observed in the spectral characteristics of eosin are caused by structural changes in albumin globules as a result of glycosylation.

Analysis of the relationships between type 2 diabetes status, glycemic control, and neuroimaging measures in the Diabetes Heart Study Mind.

Science.gov (United States)

Raffield, Laura M; Cox, Amanda J; Freedman, Barry I; Hugenschmidt, Christina E; Hsu, Fang-Chi; Wagner, Benjamin C; Xu, Jianzhao; Maldjian, Joseph A; Bowden, Donald W

2016-06-01

To examine the relationships between type 2 diabetes (T2D) status, glycemic control, and T2D duration with magnetic resonance imaging (MRI)-derived neuroimaging measures in European Americans from the Diabetes Heart Study (DHS) Mind cohort. Relationships were examined using marginal models with generalized estimating equations in 784 participants from 514 DHS Mind families. Fasting plasma glucose, glycated hemoglobin, and diabetes duration were analyzed in 682 participants with T2D. Models were adjusted for potential confounders, including age, sex, history of cardiovascular disease, smoking, educational attainment, and use of statins or blood pressure medications. Association was tested with gray and white matter volume, white matter lesion volume, gray matter cerebral blood flow, and white and gray matter fractional anisotropy and mean diffusivity. Adjusting for multiple comparisons, T2D status was associated with reduced white matter volume (p = 2.48 × 10(-6)) and reduced gray and white matter fractional anisotropy (p ≤ 0.001) in fully adjusted models, with a trend toward increased white matter lesion volume (p = 0.008) and increased gray and white matter mean diffusivity (p ≤ 0.031). Among T2D-affected participants, neither fasting glucose, glycated hemoglobin, nor diabetes duration were associated with the neuroimaging measures assessed (p > 0.05). While T2D was significantly associated with MRI-derived neuroimaging measures, differences in glycemic control in T2D-affected individuals in the DHS Mind study do not appear to significantly contribute to variation in these measures. This supports the idea that the presence or absence of T2D, not fine gradations of glycemic control, may be more significantly associated with age-related changes in the brain.

Assessment guidance of carbohydrate counting method in patients with type 2 diabetes mellitus.

Science.gov (United States)

Martins, Michelle R; Ambrosio, Ana Cristina T; Nery, Marcia; Aquino, Rita de Cássia; Queiroz, Marcia S

2014-04-01

We evaluated the application of the method of carbohydrate counting performed by 21 patients with type 2 diabetes, 1 year later attending a guidance course. Participants answered a questionnaire to assess patients' adhesion to carbohydrate counting as well as to identify habit changes and the method's applicability, and values of glycated hemoglobin were also analyzed. Most participants (76%) were females, and 25% of them had obesity degree III. There was a statistically significant decrease in glycated hemoglobin from 8.42±0.02% to 7.66±0.01% comparing values before and after counseling. We observed that although patients stated that the method was difficult they understood that carbohydrate counting could allow them make choices and have more freedom in their meals; we also verified if they understood accurately how to replace some foods used regularly in their diets and most patients correctly chose replacements for the groups of bread (76%), beans (67%) and noodles (67%). We concluded that participation in the course led to improved blood glucose control with a significant reduction of glycated hemoglobin, better understanding of food groups and the adoption of healthier eating habits. Copyright © 2013 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.

Analysis of glycation induced protein cross-linking inhibitory effects of some antidiabetic plants and spices.

Science.gov (United States)

Perera, Handunge Kumudu Irani; Handuwalage, Charith Sandaruwan

2015-06-09

Protein cross-linking which occurs towards the latter part of protein glycation is implicated in the development of chronic diabetic complications. Glycation induced protein cross-linking inhibitory effects of nine antidiabetic plants and three spices were evaluated in this study using a novel, simple, electrophoresis based method. Methanol extracts of thirteen plants including nine antidiabetic plants and three spices were used. Lysozyme and fructose were incubated at 37 °C in the presence or absence of different concentrations of plant extracts up to 31 days. Standard glycation inhibitor aminoguanidine and other appropriate controls were included. A recently established sodium dodecyl polyacrylamide gel electrophoresis (SDS-PAGE) method was used to detect the products of protein cross-linking in the incubation mixtures. High molecular weight protein products representing the dimer, trimer and tetramer of lysozyme were detected in the presence of fructose. Among the nine antidiabetic plants, seven showed glycation induced protein cross-linking inhibitory effects namely Ficus racemosa (FR) stem bark, Gymnema sylvestre (GS) leaves, Musa paradisiaca (MP) yam, Phyllanthus debilis (PD) whole plant, Phyllanthus emblica (PE) fruit, Pterocarpus marsupium (PM) latex and Tinospora cordifolia (TC) leaves. Inhibition observed with Coccinia grandis (CG) leaves and Strychnos potatorum (SP) seeds were much low. Leaves of Gymnema lactiferum (GL), the plant without known antidiabetic effects showed the lowest inhibition. All three spices namely Coriandrum sativum (CS) seeds, Cinnamomum zeylanicum (CZ) bark and Syzygium aromaticum (SA) flower buds showed cross-link inhibitory effects with higher effects in CS and SA. PD, PE, PM, CS and SA showed almost complete inhibition on the formation of cross-linking with 25 μg/ml extracts. Methanol extracts of PD, PE, PM, CS and SA have shown promising inhibitory effects on glycation induced protein cross-linking.

The in vitro effects of advanced glycation end products on basophil functions.

Science.gov (United States)

Han, Kaiyu; Suzukawa, Maho; Yamaguchi, Masao; Sugimoto, Naoya; Nakase, Yuko; Toda, Takako; Nagase, Hiroyuki; Ohta, Ken

2011-01-01

Basophils are thought to play pivotal roles in the pathogenesis of allergic reactions, but their roles in inflammation associated with systemic abnormalities such as metabolic disorders remain largely unknown. Advanced glycation end products (AGEs) are potentially important substances produced in high-glucose disease conditions. In this in vitro study, we investigated whether the biological functions of human basophils can be influenced by AGEs. We analyzed the effects of AGEs on various functions and markers of human basophils, including CD11b expression, apoptosis, degranulation, and cytokine production. Flow cytometric analysis indicated that the level of the receptor for AGEs (RAGE) on the surface of freshly isolated basophils was very low but was clearly upregulated by IL-3. Apoptosis of basophils was induced by high concentrations of glycated albumin. Although glycated albumin failed to affect the level of surface CD11b expression or to trigger degranulation or production of IL-4 and IL-13 in basophils, it dose-dependently induced IL-6 and IL-8 secretion. AGEs seem to act on human basophils; they suppress the cells' longevity but elicit secretion of inflammatory cytokines. Through these biological changes, basophils might play some roles in inflammatory conditions associated with metabolic disorders presenting elevated levels of AGEs. Copyright © 2011 S. Karger AG, Basel.

Genomic organization and evolution of the Atlantic salmon hemoglobin repertoire

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Phillips Ruth B

2010-10-01

Full Text Available Abstract Background The genomes of salmonids are considered pseudo-tetraploid undergoing reversion to a stable diploid state. Given the genome duplication and extensive biological data available for salmonids, they are excellent model organisms for studying comparative genomics, evolutionary processes, fates of duplicated genes and the genetic and physiological processes associated with complex behavioral phenotypes. The evolution of the tetrapod hemoglobin genes is well studied; however, little is known about the genomic organization and evolution of teleost hemoglobin genes, particularly those of salmonids. The Atlantic salmon serves as a representative salmonid species for genomics studies. Given the well documented role of hemoglobin in adaptation to varied environmental conditions as well as its use as a model protein for evolutionary analyses, an understanding of the genomic structure and organization of the Atlantic salmon α and β hemoglobin genes is of great interest. Results We identified four bacterial artificial chromosomes (BACs comprising two hemoglobin gene clusters spanning the entire α and β hemoglobin gene repertoire of the Atlantic salmon genome. Their chromosomal locations were established using fluorescence in situ hybridization (FISH analysis and linkage mapping, demonstrating that the two clusters are located on separate chromosomes. The BACs were sequenced and assembled into scaffolds, which were annotated for putatively functional and pseudogenized hemoglobin-like genes. This revealed that the tail-to-tail organization and alternating pattern of the α and β hemoglobin genes are well conserved in both clusters, as well as that the Atlantic salmon genome houses substantially more hemoglobin genes, including non-Bohr β globin genes, than the genomes of other teleosts that have been sequenced. Conclusions We suggest that the most parsimonious evolutionary path leading to the present organization of the Atlantic salmon

Genomic organization and evolution of the Atlantic salmon hemoglobin repertoire

Science.gov (United States)

2010-01-01

Background The genomes of salmonids are considered pseudo-tetraploid undergoing reversion to a stable diploid state. Given the genome duplication and extensive biological data available for salmonids, they are excellent model organisms for studying comparative genomics, evolutionary processes, fates of duplicated genes and the genetic and physiological processes associated with complex behavioral phenotypes. The evolution of the tetrapod hemoglobin genes is well studied; however, little is known about the genomic organization and evolution of teleost hemoglobin genes, particularly those of salmonids. The Atlantic salmon serves as a representative salmonid species for genomics studies. Given the well documented role of hemoglobin in adaptation to varied environmental conditions as well as its use as a model protein for evolutionary analyses, an understanding of the genomic structure and organization of the Atlantic salmon α and β hemoglobin genes is of great interest. Results We identified four bacterial artificial chromosomes (BACs) comprising two hemoglobin gene clusters spanning the entire α and β hemoglobin gene repertoire of the Atlantic salmon genome. Their chromosomal locations were established using fluorescence in situ hybridization (FISH) analysis and linkage mapping, demonstrating that the two clusters are located on separate chromosomes. The BACs were sequenced and assembled into scaffolds, which were annotated for putatively functional and pseudogenized hemoglobin-like genes. This revealed that the tail-to-tail organization and alternating pattern of the α and β hemoglobin genes are well conserved in both clusters, as well as that the Atlantic salmon genome houses substantially more hemoglobin genes, including non-Bohr β globin genes, than the genomes of other teleosts that have been sequenced. Conclusions We suggest that the most parsimonious evolutionary path leading to the present organization of the Atlantic salmon hemoglobin genes involves

Advanced glycation end product (AGE) modified proteins in tears of diabetic patients.

Science.gov (United States)

Zhao, Zhenjun; Liu, Jingfang; Shi, Bingyin; He, Shuixiang; Yao, Xiaoli; Willcox, Mark D P

2010-08-11

High glucose level in diabetic patients may lead to advanced glycation end product (AGE) modified proteins. This study investigated AGE modified proteins in tears and compared their levels in diabetic patients (DM) with non-diabetic controls (CTL). Basal tears were collected from DM with (DR) or without (DNR) retinopathy and CTL. Total AGE modified proteins were detected quantitatively by a dot immunobinding assay. The AGE modified proteins were separated in 1D- and 2D-SDS gels and detected by western-blotting. The individual AGE modified proteins were also compared between groups using densitometry. Compared with the CTL group, tear concentrations of AGE modified proteins were significantly elevated in DR and DNR groups. The concentration of AGE modified proteins in diabetic tears were positively correlated with AGE modified hemoglobin (HbA1c) and postprandial blood glucose level (PBG). Western blotting of AGE modified proteins from 1D-SDS gels showed several bands, the major one at around 60 kDa. The intensities of AGE modified protein bands were higher in DM tears than in CTL tears. Western blotting from 2D-SDS gels showed a strongly stained horizontal strip, which corresponded to the major band in 1D-SDS gels. Most of the other AGE modified protein species were within molecular weight of 30-60 kDa, PI 5.2-7.0. Densitometry analysis demonstrated several AGE modified proteins were elevated in DR or DNR tears. Total and some individual AGE modified proteins were elevated in DM tears. AGE modified proteins in tears may be used as biomarkers to diagnose diabetes and/or diabetic retinopathy.

Symbiotic and nonsymbiotic hemoglobin genes of Casuarina glauca

DEFF Research Database (Denmark)

Jacobsen-Lyon, K; Jensen, Erik Østergaard; Jørgensen, Jan-Elo

1995-01-01

Casuarina glauca has a gene encoding hemoglobin (cashb-nonsym). This gene is expressed in a number of plant tissues. Casuarina also has a second family of hemoglobin genes (cashb-sym) expressed at a high level in the nodules that Casuarina forms in a nitrogen-fixing symbiosis with the actinomycete...... of the Casuarina gene. The finding that the nonsymbiotic Casuarina gene is also correctly expressed in L. corniculatus suggests to us that a comparable non-symbiotic hemoglobin gene will be found in legume species. Udgivelsesdato: 1995-Feb...

Glycation and transglutaminase mediated glycosylation of fish gelatin peptides with glucosamine enhance bioactivity.

Science.gov (United States)

Hong, Pui Khoon; Gottardi, Davide; Ndagijimana, Maurice; Betti, Mirko

2014-01-01

A mixture of novel glycopeptides from glycosylation between cold water fish skin gelatin hydrolysates and glucosamine (GlcN) via transglutaminase (TGase), as well as glycation between fish gelatin hydrolysate and GlcN were identified by their pattern of molecular distribution using MALDI-TOF-MS. Glycated/glycosylated hydrolysates showed superior bioactivity to their original hydrolysates. Alcalase-derived fish skin gelatin hydrolysate glycosylated with GlcN in the presence of TGase at 25°C (FAT25) possessed antioxidant activity when tested in a linoleic acid oxidation system, when measured according to its 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging activity and when tested at the cellular level with human hepatocarcinoma (HepG2) cells as target cells. In addition, Alcalase-derived glycosylated hydrolysates showed specificity toward the inhibition of Escherichia coli (E. coli). The Flavourzyme-derived glycopeptides prepared at 37°C (FFC37 and FFT37) showed better DPPH scavenging activity than their native hydrolysates. The glycated Flavourzyme-derived hydrolysates were found to act as potential antimicrobial agents when incubated with E. coli and Bacillus subtilis. Copyright © 2013 Elsevier Ltd. All rights reserved.

Radiation - induced changes in the optical properties of hemoglobin molecule

International Nuclear Information System (INIS)

Selim, N.S; El-Marakby, S.M.

2009-01-01

Adult male albino rats were exposed to different doses of gamma radiation from Cs-137 source. Hemoglobin samples were analyzed 24 hrs after irradiation. The UV-visible spectrum of hemoglobin molecule was measured in the range 200 to 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

Hemoglobin levels in persons with depressive and/or anxiety disorders

NARCIS (Netherlands)

Lever-van Milligen, Bianca A.; Vogelzangs, Nicole; Smit, Johannes H.; Penninx, Brenda W. J. H.

Objective: Both low and high hemoglobin levels lead to more physical diseases, and both are linked to mortality. Low hemoglobin, often classified as anemia, has also been linked to more depressive symptoms, but whether both hemoglobin extremes are associated with depressive disorder and potentially

Dietary advanced glycation endproducts

DEFF Research Database (Denmark)

Poulsen, Malene Wibe

High heat cooking induces flavor, aroma, and color of food, but leads to formation of advanced glycation endproducts (AGEs) by the Maillard reaction. In addition to the formation in food, AGEs are also formed in vivo, and increased endogenous formation of AGEs has been linked to diabetic...... on postprandial subjective appetite sensations, appetite hormones, and markers of inflammation of two cooking methods that respectively induce or limit AGE formation were investigated in healthy overweight individuals. It was concluded that the meals affected subjective appetite sensations similarly, but the high...... sensitivity of cooking methods that induce or limit AGE formation were investigated in healthy overweight women. It was concluded that insulin sensitivity was improved with use of low heat cooking methods, compared with high heat cooking methods. In a rat study, effects on expression of AGE receptors, insulin...

Titania nanotubes decorated with gold nanoparticles for electrochemiluminescent biosensing of glycosylated hemoglobin

Energy Technology Data Exchange (ETDEWEB)

Zhao, Qun [Institute of Analytical Chemistry, Dushu Lake Campus, Soochow University, Industrial Park, Suzhou, 215123 (China); College of Chemistry and Chemical Engineering, Nantong University, Nantong, 226019 (China); Tang, Shan [Institute of Analytical Chemistry, Dushu Lake Campus, Soochow University, Industrial Park, Suzhou, 215123 (China); Fang, Chen [Institute of Analytical Chemistry, Dushu Lake Campus, Soochow University, Industrial Park, Suzhou, 215123 (China); Second Affiliated Hospital, Soochow University, Suzhou, 215004 (China); Tu, Yi-Feng, E-mail: tuyf@suda.edu.cn [Institute of Analytical Chemistry, Dushu Lake Campus, Soochow University, Industrial Park, Suzhou, 215123 (China)

2016-09-14

A glycated hemoglobin (HbA1c) biosensor with high performance has been constructed in this work. Here the fructosyl amino acid oxidase was immobilized onto a pre-functionalized indium tin oxide glass with titania nanotubes decorated with gold nanoparticles. The property of nanocomposite was characterized by transmission electromicroscopy, scanning electron microscopy, electrochemistry and spectroscopy. Under the optimum conditions, fructosyl valine was detected by this biosensor. It exhibited a linear detection range from 4.0 × 10{sup −9} M to 7.2 × 10{sup −7} M, and a limit of detection for 3.8 × 10{sup −9} M at the signal-to-noise ratio of 3. Thus the HbA1c level in whole blood samples of healthy individuals or diabetic patients were evaluated with designed biosensor after pre-treatment of hydrolysis. The results of our detection were closely consistent with that of the standard method. At the same time, our biosensor has some advantages including high sensitivity, disposable usage and low cost, which implies its great promising application in point-of-care testing of HbA1c. - Highlights: • The enhanced electrochemiluminescence of luminol by AuNPs/TiNTs. • An ECL biosensor for HbA1c assay with ultra-high sensitivity. • A promising disposable device for diabetic diagnosis and treatment even for POCT. • The excellent regression of detected results with gold-standard method.

Titania nanotubes decorated with gold nanoparticles for electrochemiluminescent biosensing of glycosylated hemoglobin

International Nuclear Information System (INIS)

Zhao, Qun; Tang, Shan; Fang, Chen; Tu, Yi-Feng

2016-01-01

A glycated hemoglobin (HbA1c) biosensor with high performance has been constructed in this work. Here the fructosyl amino acid oxidase was immobilized onto a pre-functionalized indium tin oxide glass with titania nanotubes decorated with gold nanoparticles. The property of nanocomposite was characterized by transmission electromicroscopy, scanning electron microscopy, electrochemistry and spectroscopy. Under the optimum conditions, fructosyl valine was detected by this biosensor. It exhibited a linear detection range from 4.0 × 10"−"9 M to 7.2 × 10"−"7 M, and a limit of detection for 3.8 × 10"−"9 M at the signal-to-noise ratio of 3. Thus the HbA1c level in whole blood samples of healthy individuals or diabetic patients were evaluated with designed biosensor after pre-treatment of hydrolysis. The results of our detection were closely consistent with that of the standard method. At the same time, our biosensor has some advantages including high sensitivity, disposable usage and low cost, which implies its great promising application in point-of-care testing of HbA1c. - Highlights: • The enhanced electrochemiluminescence of luminol by AuNPs/TiNTs. • An ECL biosensor for HbA1c assay with ultra-high sensitivity. • A promising disposable device for diabetic diagnosis and treatment even for POCT. • The excellent regression of detected results with gold-standard method.

Manipulation of hemoglobin expression affects Arabidopsis shoot organogenesis

DEFF Research Database (Denmark)

Wang, Yaping; Elhiti, Mohamed; Hebelstrup, Kim

2011-01-01

Over the past few years non-symbiotic plant hemoglobins have been described in a variety of plant species where they fulfill several functions ranging from detoxification processes to basic aspects of plant growth and post-embryonic development. To date no information is available on the role...... of hemoglobins during invitro morphogenesis. Shoot organogenesis was induced in Arabidopsis lines constitutively expressing class 1, 2 and 3 hemoglobins (GLB1, 2 and 3) and lines in which the respective genes were either downregulated by RNAi (GLB1) or knocked out (GLB2 and GLB3). The process was executed......, 15, and 16), feed-back repressors of the cytokinin pathway, was repressed in both hemoglobin over-expressors whereas that of several Type-B ARRs (ARR2, 12, and 13), transcription activators of cytokinin-responsive genes, was induced. Such changes enhanced the sensitivity of the root explants...

Studies on radiation induced changes in bovine hemoglobin type A

International Nuclear Information System (INIS)

Wdzieczak, J.; Duda, W.; Leyko, W.

1978-01-01

In this paper the structural and functional changes of gamma irradiated bovine hemoglobin are presented. Aqueous solutions/1%/of HbO 2 were irradiated in air with doses ranging from 1 to 4 Mrad. Isoelectric focusing indicated change of the charge of irradiated hemoglobin. The isoelectric point of hemoglobin was displaced towards more acid values with increasing doses, up from 1 Mrad. Fingerprint analysis and peptide column chromatography of irradiated hemoglobin demonstrated disturbances increasing with the dose. These changes were confirmed by amino acid analysis which showed that Cys, Met, Trp, His, Pro and Tyr residues were destroyed or modified following irradiation. At doses exceeding 1 Mrad the irradiated solutions of hemoglobin showed a decrease of heme-heme interaction and an increase of affinity for oxygen. Differences observed in oxygen-dissociation curves seem to be correlated with the radiation induced destruction of amino acid residues which are responsible for the functional properties of hemoglobin. (auth.)

A Perspective on Reagent Diversity and Non-covalent Binding of Reactive Carbonyl Species (RCS and Effector Reagents in Non-enzymatic Glycation (NEG: Mechanistic Considerations and Implications for Future Research

Directory of Open Access Journals (Sweden)

Kenneth J. Rodnick

2017-06-01

Full Text Available This perspective focuses on illustrating the underappreciated connections between reactive carbonyl species (RCS, initial binding in the nonenzymatic glycation (NEG process, and nonenzymatic covalent protein modification (here termed NECPM. While glucose is the central species involved in NEG, recent studies indicate that the initially-bound glucose species in the NEG of human hemoglobin (HbA and human serum albumin (HSA are non-RCS ring-closed isomers. The ring-opened glucose, an RCS structure that reacts in the NEG process, is most likely generated from previously-bound ring-closed isomers undergoing concerted acid/base reactions while bound to protein. The generation of the glucose RCS can involve concomitantly-bound physiological species (e.g., inorganic phosphate, water, etc.; here termed effector reagents. Extant NEG schemes do not account for these recent findings. In addition, effector reagent reactions with glucose in the serum and erythrocyte cytosol can generate RCS (e.g., glyoxal, glyceraldehyde, etc.. Recent research has shown that these RCS covalently modify proteins in vivo via NECPM mechanisms. A general scheme that reflects both the reagent and mechanistic diversity that can lead to NEG and NECPM is presented here. A perspective that accounts for the relationships between RCS, NEG, and NECPM can facilitate the understanding of site selectivity, may help explain overall glycation rates, and may have implications for the clinical assessment/control of diabetes mellitus. In view of this perspective, concentrations of ribose, fructose, Pi, bicarbonate, counter ions, and the resulting RCS generated within intracellular and extracellular compartments may be of importance and of clinical relevance. Future research is also proposed.

Anti-glycation and anti-oxidation properties of Capsicum frutescens and Curcuma longa fruits: possible role in prevention of diabetic complication.

Science.gov (United States)

Khan, Ibrar; Ahmad, Haroon; Ahmad, Bashir

2014-09-01

The accumulation of advanced glycationend products (AGE's) in the body, due to the non-enzymatic glycation of proteins is associated with several pathological conditions like aging and diabetes mellitus. Hence a plant having anti-glycation and anti-oxidation potentials may serve as therapeutic agent for diabetic complications and aging. In this study the anti-glycation and anti-oxidation properties of crude methanolic extracts of fruits of Capsicum frutescens and Curcuma longa were investigated. Among the two C. frutescens had more anti-glycation ability with a minimum inhibitory concentration (MIC50) of 90βg/mLas compared to 324βg/mL MIC50 of C. longa. Curcuma longa had the more anti-oxidation potential i.e. 35.01, 30.83 and 28.08% at 0.5mg, 0.25mg and 0.125mg respectively.

Hemoglobin Values During Pregnancy | Leffler | Nigerian Medical ...

African Journals Online (AJOL)

It is known that the iron turnover in expectant mothers is up to three times that of an average adult. This is reflected in lower hemoglobin levels. The study showed that hemoglobin levels can be maintained by taking Bio-Strath®, provided that the patients' diet contains adequate fresh fruits and vegetables, whole grains, lean ...

Clinical, hematological and genetic data of a cohort of children with hemoglobin SD

Directory of Open Access Journals (Sweden)

Paulo do Val Rezende

Full Text Available ABSTRACT INTRODUCTION: The hemoglobin FSD is very uncommon in newborn screening programs for sickle cell disease. In the program of Minas Gerais, Brazil, the clinical course of children with hemoglobin SD was observed to be heterogeneous. The objective of this study was to estimate the incidence (1999-2012 and to describe the natural history of a cohort of newborns with hemoglobin SD. METHODS: Isoelectric focusing was the primary method used in newborn screening. Polymerase chain reaction-restriction fragment length polymorphism and gene sequencing were used to identify mutant alleles and for haplotyping. Gap-polymerase chain reaction was used to detect alpha-thalassemia. RESULTS: Eleven cases of hemoglobin S/D-Punjab and eight of Hb S-Korle Bu were detected. Other variants with hemoglobin D mobility were not identified. All hemoglobin D-Punjab and hemoglobin Korle Bu alleles were associated with haplotype I. Among the children with hemoglobin S/D-Punjab, there were four with the ßS CAR haplotype, six with the Benin haplotype, and one atypical. Results of laboratory tests for hemoglobin S/D-Punjab and hemoglobin S-Korle Bu were: hemoglobin 8.0 and 12.3 g/dL (p-value <0.001, leukocyte count 13.9 × 109/L and 10.5 × 109/L (p-value = 0.003, reticulocytes 7.5% and 1.0% (p-value <0.001, hemoglobin F concentration 16.1% and 6.9% (p-value = 0.001 and oxygen saturation 91.9% and 97% (p-value = 0.002, respectively. Only hemoglobin S/D-Punjab children had acute pain crises and needed blood transfusions or hydroxyurea. Those with the Benin ßS haplotype had higher total hemoglobin and hemoglobin F concentrations compared to the CAR haplotype. Transcranial Doppler was normal in all children. CONCLUSION: The clinical course and blood cell counts of children with hemoglobin S/D-Punjab were very similar to those of hemoglobin SS children. In contrast, children with hemoglobin S-Korle Bu had clinical course and blood cell counts like children with the sickle

Oxidative stress in preeclampsia and the role of free fetal hemoglobin

Directory of Open Access Journals (Sweden)

Stefan Rocco Hansson

2015-01-01

Full Text Available Preeclampsia is a leading cause of pregnancy complications and affects 3–7 % of pregnant women. This review summarizes the current knowledge of a new potential etiology of the disease, with a special focus on hemoglobin-induced oxidative stress. Furthermore, we also suggest hemoglobin as a potential target for therapy. Gene and protein profiling studies have shown increased expression and accumulation of free fetal hemoglobin in the preeclamptic placenta. Predominantly due to oxidative damage to the placental barrier, fetal hemoglobin leaks over to the maternal circulation. Free hemoglobin and its metabolites are toxic in several ways; a ferrous hemoglobin (Fe2+ binds strongly to the vasodilator nitric oxide and reduces the availability of free nitric oxide, which results in vasoconstriction, b hemoglobin (Fe2+ with bound oxygen spontaneously generates free oxygen radicals and c the heme groups create an inflammatory response by inducing activation of neutrophils and cytokine production. The endogenous protein α1-microglobulin, with radical and heme binding properties, has shown both ex vivo and in vivo to have the ability to counteract free hemoglobin-induced placental and kidney damage. Oxidative stress in general, and more specifically fetal hemoglobin-induced oxidative stress, could play a key role in the pathology of preeclampsia seen both in the placenta and ultimately in the maternal endothelium.

Conformational changes in hemoglobin triggered by changing the iron charge

International Nuclear Information System (INIS)

Croci, S.; Achterhold, K.; Ortalli, I.; Parak, F. G.

2008-01-01

In this work the hemoglobin conformational changes induced by changing the iron charge have been studied and compared with Myoglobin. Moessbauer spectroscopy was used to follow the change of the iron conformation. In order to compare the conformational relaxation of hemoglobin and myoglobin, and to study a possible influence of the quaternary structure, an intermediate metastable state of hemoglobin has been created by low temperature X-ray irradiation of methemoglobin. The irradiation reduces the Fe(III) of the heme groups to Fe(II) Low Spin, where the water is still bound on the sixth coordination. Heating cycles performed at temperatures from 140 K to 200 K allow the molecules to overcome an activation energy barrier and to relax into a stable conformation such as deoxy-hemoglobin or carboxy-hemoglobin, if CO is present. Slightly different structures (conformational substates) reveal themselves as a distribution of energy barriers (ΔG). The distribution of the activation energy, for the decay of the Fe(II) Low Spin intermediate, has been fitted with a Gaussian. For comparison, published myoglobin data were re-analysed in the same way. The average energy value at characteristic temperature is very similar in case of myoglobin and hemoglobin. The larger Gaussian energy distribution for myoglobin with respect to hemoglobin shows that more conformational substates are available. This may be caused by a larger area exposed to water. In hemoglobin, part of the surface of the chains is not water accessible due to the quaternary structure.

[Therapeutically active dressings--biomaterials in a study of collagen glycation].

Science.gov (United States)

Pielesz, Anna; Paluch, Jadwiga

2012-01-01

Active dressings (biomaterials, hydrogels) are cross-linked three-dimensional macromolecular networks. One of the most important properties of active dressings, is their ability for controlled uptake, release and retention of molecules. The formation of advanced glycation end products AGEs progressively increases with normal aging. However, AGE products are formed at accelerated rates in age and stress-related diseases (burns, in wound healing) and also in vitro. The aim will be also to develop a series of gels showing ability of controlled uptake, release and retention of molecules. The hydrogels can be used as biologically and therapeutically (antibacterial and anticancer) active biomaterials. The following materials and reagents were used in the examination: dried plants: Equisetum arvense L., Pulmonaria officinalis L., Agropyron repens. Non-defatted films were extracted from the dried plants. The suspension was stirred and extracted. Temperature was controlled using a water bath. The filtrate was vacuum condensed. The gelling precipitate was poured onto Petri plates and dried. The swelling ratio and the percent loading were calculated. The released amount of CaCl2 at different time intervals was determined by measuring the conductivity. The extent of glycation in collagen was measured. Novel types of swelling hydrogels have been prepared from dried plants and alginic acid. The active dressings showed swelling in aqueous medium, swelling characteristics were dependent on the chemical composition of hydrogel. The hydrogels were also loaded with CaCl2 and their potential for release was judged by measuring conductivity. The activity of hydrogels--active dressings on collagen incubated with glucose showed an decrease in glycation. So, hydrogels--active dressings, a known antiglycating agent which have therapeutic role in wound healing.

A thermodynamical measure of cooperativity: application to hemoglobin

International Nuclear Information System (INIS)

Jacchieri, S.G.; Ferreira, R.C.

1984-01-01

A comparative analysis of the heat requirements for dioxygen exchange is made for hemoglobin and myoglobin, the latter taken as the prototype of the vertebrate hemoglobin's ancestor. it is shown that cooperativity manifests itself also in terms of energy utilization. (Author) [pt

Yeast Metabolites of Glycated Amino Acids in Beer.

Science.gov (United States)

Hellwig, Michael; Beer, Falco; Witte, Sophia; Henle, Thomas

2018-06-01

Glycation reactions (Maillard reactions) during the malting and brewing processes are important for the development of the characteristic color and flavor of beer. Recently, free and protein-bound Maillard reaction products (MRPs) such as pyrraline, formyline, and maltosine were found in beer. Furthermore, these amino acid derivatives are metabolized by Saccharomyces cerevisiae via the Ehrlich pathway. In this study, a method was developed for quantitation of individual Ehrlich intermediates derived from pyrraline, formyline, and maltosine. Following synthesis of the corresponding reference material, the MRP-derived new Ehrlich alcohols pyrralinol (up to 207 μg/L), formylinol (up to 50 μg/L), and maltosinol (up to 6.9 μg/L) were quantitated for the first time in commercial beer samples by reverse phase high performance liquid chromatography tandem mass spectrometry in the multiple reaction monitoring mode. This is equivalent to ca. 20-40% of the concentrations of the parent glycated amino acids. The metabolites were almost absent from alcohol-free beers and malt-based beverages. Two previously unknown valine-derived pyrrole derivatives were characterized and qualitatively identified in beer. The metabolites investigated represent new process-induced alkaloids that may influence brewing yeast performance due to structural similarities to quorum sensing and metal-binding molecules.

The clinical relevance of assessing advanced glycation endproducts accumulation in diabetes

NARCIS (Netherlands)

Meerwaldt, Robbert; Links, Thera; Zeebregts, Clark; Tio, Rene; Hillebrands, Jan-Luuk; Smit, Andries

2008-01-01

Cardiovascular disease is the major cause of morbidity and mortality associated with diabetes. There is increasing evidence that advanced glycation endproducts (AGEs) play a pivotal role in atherosclerosis, in particular in diabetes. AGE accumulation is a measure of cumulative metabolic and

Increased levels of advanced glycation end products positively correlate with iron overload and oxidative stress markers in patients with β-thalassemia major.

Science.gov (United States)

Mirlohi, Maryam Sadat; Yaghooti, Hamid; Shirali, Saeed; Aminasnafi, Ali; Olapour, Samaneh

2018-04-01

The impaired biosynthesis of the β-globin chain in β-thalassemia leads to the accumulation of unpaired alpha globin chains, failure in hemoglobin formation, and iron overload due to frequent blood transfusion. Iron excess causes oxidative stress and massive tissue injuries. Advanced glycation end products (AGEs) are harmful agents, and their production accelerates in oxidative conditions. This study was conducted on 45 patients with major β-thalassemia who received frequent blood transfusions and chelation therapy and were compared to 40 healthy subjects. Metabolic parameters including glycemic and iron indices, hepatic and renal functions tests, oxidative stress markers, and AGEs (carboxymethyl-lysine and pentosidine) levels were measured. All parameters were significantly increased in β-thalassemia compared to the control except for glutathione levels. Blood glucose, iron, serum ferritin, non-transferrin-bound iron (NTBI), MDA, soluble form of low-density lipoprotein receptor, glutathione peroxidase, total reactive oxygen species (ROS), and AGE levels were significantly higher in the β-thalassemia patients. Iron and ferritin showed a significant positive correlation with pentosidine (P overload in β-thalassemia major patients and highlight the enhanced formation of AGEs, which may play an important role in the pathogenesis of β-thalassemia major.

Changes in hemoglobin-oxygen affinity with shape variations of red blood cells

Science.gov (United States)

Chowdhury, Aniket; Dasgupta, Raktim; Majumder, Shovan K.

2017-10-01

Shape variations of red blood cells (RBCs) are known to occur upon exposure to various drugs or under diseased conditions. The commonly observed discocytic RBCs can be transformed to echinocytic or stomatocytic shape under such conditions. Raman spectra of the three major shape variations, namely discocyte, echinocyte, and stomatocyte, of RBCs were studied while subjecting the cells to oxygenated and deoxygenated conditions. Analysis of the recorded spectra suggests an increased level of hemoglobin (Hb)-oxygen affinity for the echinocytes. Also, some level of Hb degradation could be noticed for the deoxygenated echinocytes. The effects may arise from a reduced level of intracellular adenosine triphosphate in echinocytic cells and an increased fraction of submembrane Hb.

INTRINSIC REGULATION OF HEMOGLOBIN EXPRESSION BY VARIABLE SUBUNIT INTERFACE STRENGTHS

Science.gov (United States)

Manning, James M.; Popowicz, Anthony M.; Padovan, Julio C.; Chait, Brian T.; Manning, Lois R.

2012-01-01

SUMMARY The expression of the six types of human hemoglobin subunits over time is currently considered to be regulated mainly by transcription factors that bind to upstream control regions of the gene (the “extrinsic” component of regulation). Here we describe how subunit pairing and further assembly to tetramers in the liganded state is influenced by the affinity of subunits for one another (the “intrinsic” component of regulation). The adult hemoglobin dimers have the strongest subunit interfaces and the embryonic hemoglobins are the weakest with fetal hemoglobins of intermediate strength, corresponding to the temporal order of their expression. These variable subunit binding strengths and the attenuating effects of acetylation contribute to the differences with which these hemoglobin types form functional O2-binding tetramers consistent with gene switching. PMID:22129306

Diffusion coefficients of oxygen and hemoglobin as obtained simultaneously from photometric determination of the oxygenation of layers of hemoglobin solutions

NARCIS (Netherlands)

Spaan, J. A.; Kreuzer, F.; van Wely, F. K.

1980-01-01

The oxygenation of layers of deoxygenated hemoglobin solutions after a sudden exposure to a gas containing oxygen at a partial pressure P1 has been studied by a photometric method. Layer thicknesses varied between 50 and 250 micron, hemoglobin concentrations between 0.1 and 0.34kg/l, and oxygen

Mechanisms of the adjuvant effect of hemoglobin in experimental peritonitis. VII. Hemoglobin does not inhibit clearance of Escherichia coli from the peritoneal cavity

International Nuclear Information System (INIS)

Dunn, D.L.; Barke, R.A.; Lee, J.T. Jr.; Condie, R.M.; Humphrey, E.W.; Simmons, R.L.

1983-01-01

Hemoglobin has been shown to be a potent adjuvant in experimental Escherichia coli peritonitis, although a satisfactory mechanistic rationale is still obscure. Hemoglobin has been thought to impair intraperitoneal neutrophil function, delay clearance of bacteria from the peritoneal cavity by the normal absorptive mechanisms, or directly enhance bacterial growth. Using highly purified stroma-free hemoglobin (SFHgb), we have largely discounted any direct effect of hemoglobin on peritoneal white blood cell function. In the present study, we confirmed that uncontrolled proliferation of bacteria takes place in the presence of hemoglobin in the peritoneal cavity. Nonviable 5-iododeoxyuridine 125 I-labelled bacteria were then used to directly study peritoneal clearance kinetics, eliminating the problem of bacterial growth. SFHgb had no influence on the removal of intraperitoneal bacteria. The rate of bloodstream appearance of radiolabel was similar with or without intraperitoneal SFHgb. Thus, SFHgb does not prevent clearance of bacteria from the peritoneal cavity by interfering with normal host clearance mechanisms. SFHgb may act as a bacterial growth adjuvant, either by serving as a bacterial nutrient or by suitably modifying the environment so that extensive bacterial proliferation can occur. The latter hypothesis appears to be an area in which investigation concerning the adjuvant effect of hemoglobin may prove most fruitful

Effect of aqueous bark extract of Garuga pinnata Roxb. in streptozotocin-nicotinamide induced type-II diabetes mellitus.

Science.gov (United States)

Shirwaikar, Annie; Rajendran, K; Barik, Rakesh

2006-09-19

A study was undertaken to evaluate the antihyperglycemic activity of aqueous extract of bark of Garuga pinnata Roxb. (Burseraceae). The various parameters studied included fasting blood sugar levels, serum lipid levels, liver glycogen content, serum insulin level and glycated hemoglobin in diabetic and normal rats. Streptozotocin-nicotinamide was used to induce type-II diabetes mellitus. Treatment with the extract at two dose levels showed a significant increase in the liver glycogen and serum insulin level and a significant decrease in fasting blood glucose and glycated hemoglobin levels. The total cholesterol and serum triglycerides levels were also significantly reduced and the HDL cholesterol levels were significantly increased upon treatment with the extract thus proving the potent antidiabetic property of the plant.

Acute hydrodynamic damage induced by SPLITT fractionation and centrifugation in red blood cells.

Science.gov (United States)

Urbina, Adriana; Godoy-Silva, Ruben; Hoyos, Mauricio; Camacho, Marcela

2016-05-01

Though blood bank processing traditionally employs centrifugation, new separation techniques may be appealing for large scale processes. Split-flow fractionation (SPLITT) is a family of techniques that separates in absence of labelling and uses very low flow rates and force fields, and is therefore expected to minimize cell damage. However, the hydrodynamic stress and possible consequent damaging effects of SPLITT fractionation have not been yet examined. The aim of this study was to investigate the hydrodynamic damage of SPLITT fractionation to human red blood cells, and to compare these effects with those induced by centrifugation. Peripheral whole blood samples were collected from healthy volunteers. Samples were diluted in a buffered saline solution, and were exposed to SPLITT fractionation (flow rates 1-10 ml/min) or centrifugation (100-1500 g) for 10 min. Cell viability, shape, diameter, mean corpuscular hemoglobin, and membrane potential were measured. Under the operating conditions employed, both SPLITT and centrifugation maintained cell viability above 98%, but resulted in significant sublethal damage, including echinocyte formation, decreased cell diameter, decreased mean corpuscular hemoglobin, and membrane hyperpolarization which was inhibited by EGTA. Wall shear stress and maximum energy dissipation rate showed significant correlation with lethal and sublethal damage. Our data do not support the assumption that SPLITT fractionation induces very low shear stress and is innocuous to cell function. Some changes in SPLITT channel design are suggested to minimize cell damage. Measurement of membrane potential and cell diameter could provide a new, reliable and convenient basis for evaluation of hydrodynamic effects on different cell models, allowing identification of optimal operating conditions on different scales. Copyright © 2016 Elsevier B.V. All rights reserved.

Advanced glycation end products in clinical nephrology.

Science.gov (United States)

Kalousová, M; Zima, T; Tesar, V; Stípek, S; Sulková, S

2004-01-01

As a result of oxidative and carbonyl stress, advanced glycation end products (AGEs) are involved in the pathogenesis of severe and frequent diseases and their fatal vascular/cardiovascular complications, i.e. diabetes mellitus and its complications (nephropathy, angiopathy, neuropathy and retinopathy, renal failure and uremic and dialysis-associated complications), atherosclerosis and dialysis-related amyloidosis, neurodegenerative diseases, and rheumatoid arthritis. They are formed via non-enzymatic glycation which is specifically enhanced through the presence of oxidative and carbonyl stress, and their ability to form glycoxidation products in peptide and protein structures finally modulating or inducing biological reactivity. Food can be another source of AGEs; however, high serum AGEs in hemodialysis patients might reflect nutritional status better. Several methods of renal replacement therapy have been studied in connection with the AGE removal, but unfortunately the possibilities are still unsatisfactory even if high flux dialysis, hemofiltration, or hemodiafiltration give better results than conventional low flux dialysis. AGEs are currently being studied in the patients on peritoneal dialysis as their precursors can be formed in the dialysis fluid. AGEs can cause damage to the peritoneum and so a loss of ultrafiltration capacity. Many compounds give promising results in AGE inhibition (inhibition of formation of AGEs, inhibition of their action or degradation of AGEs), are tested for these properties, and eventually undergo clinical studies (e.g. aminoguanidine, OPB-9195, pyridoxamine, antioxidants, N-phenacylthiazolium bromide, antihypertensive drugs, angiotensin-converting enzyme inhibitors and angiotensin II receptor-1 antagonists). Copyright 2004 S. Karger AG, Basel

Plant hemoglobins: Important players at the crossroads between oxygen and nitric oxide

DEFF Research Database (Denmark)

Gupta, Kapuganti J; Hebelstrup, Kim; Mur, Luis A J

2011-01-01

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...... at high O2 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....

Effects of alagebrium, an advanced glycation endproduct breaker, on exercise tolerance and cardiac function in patients with chronic heart failure

NARCIS (Netherlands)

Hartog, Jasper W. L.; Willemsen, Suzan; van Veldhuisen, Dirk J.; Posma, Jan L.; van Wijk, Leen M.; Hummel, Yoran M.; Hillege, Hans L.; Voors, Adriaan A.

Aims Advanced glycation endproducts (AGEs) have been associated with the development and progression of chronic heart failure (CHF). Advanced glycation endproducts-crosslink breakers might be of benefit in HF, but only small-scale and uncontrolled data are available. Our aim was to conduct a

Reference values for the Chinese population of skin autofluorescence as a marker of advanced glycation end products accumulated in tissue

NARCIS (Netherlands)

Yue, X.; Hu, H.; Koetsier, M.; Graaff, R.; Han, C.

Aim Advanced glycation end products play an important role in the pathophysiology of several chronic and age-related diseases, especially diabetes mellitus. Skin autofluorescence is a non-invasive method for assessing levels of tissue advanced glycation end products. This study aims to establish the

Testing isotopic labeling with [¹³C₆]glucose as a method of advanced glycation sites identification.

Science.gov (United States)

Kielmas, Martyna; Kijewska, Monika; Stefanowicz, Piotr; Szewczuk, Zbigniew

2012-12-01

The Maillard reaction occurring between reducing sugars and reactive amino groups of biomolecules leads to the formation of a heterogeneous mixture of compounds: early, intermediate, and advanced glycation end products (AGEs). These compounds could be markers of certain diseases and of the premature aging process. Detection of Amadori products can be performed by various methods, including MS/MS techniques and affinity chromatography on immobilized boronic acid. However, the diversity of the structures of AGEs makes detection of these compounds more difficult. The aim of this study was to test a new method of AGE identification based on isotope (13)C labeling. The model protein (hen egg lysozyme) was modified with an equimolar mixture of [(12)C(6)]glucose and [(13)C(6)]glucose and then subjected to reduction of the disulfide bridges followed by tryptic hydrolysis. The digest obtained was analyzed by LC-MS. The glycation products were identified on the basis of characteristic isotopic patterns resulting from the use of isotopically labeled glucose. This method allowed identification of 38 early Maillard reaction products and five different structures of the end glycation products. This isotopic labeling technique combined with LC-MS is a sensitive method for identification of advanced glycation end products even if their chemical structure is unknown. Copyright © 2012 Elsevier Inc. All rights reserved.

Characteristics and enhanced antioxidant activity of glycated Morchella esculenta protein isolate

Directory of Open Access Journals (Sweden)

Qiang ZHANG

Full Text Available Abstract Morchella esculenta (L Pers. is a highly valued edible and medicinal fungus that remains underutilized. For this study, the effects of glycation treatment on antioxidant activity and characteristics of the M. esculenta protein isolate (MPI were investigated via the Maillard reaction. Conjugation between MPI and xylose was proven via UV-vis, FT-IR, intrinsic fluorescence analysis, and SDS-PAGE. Amino acid analysis revealed involvement of lysine, arginine and tyrosine in MPI, forming a covalent cross-link with xylose. Differential scanning calorimetry (DSC results showed that glycated MPI (MPIG possesses a more favorable thermal stability compared to native MPI (MPIN, heated MPI (MPIH and an unheated mixture of MPI and xylose (MPI-XM. MPIG exhibited significantly enhanced antioxidant activity compared to MPIN, MPIH, and MPI-XM. These results indicate MPIG can serve as a promising novel source of nutraceutical and functional ingredients that exert antioxidant activity.

Molecular Mechanism of AHSP-Mediated Stabilization of Alpha-Hemoglobin

Energy Technology Data Exchange (ETDEWEB)

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

2005-01-01

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

Biophysical Monitoring and dose response characteristics of irradiated hemoglobin

International Nuclear Information System (INIS)

Elshemey, W.M; Selim, N.S.; Desouky, O.

2003-01-01

The present work aims to move a step forward towards a deeper understanding of the scattering of x-ray, from lyophilized biological samples. Comparative study has been performed using LAXS and UV-visible spectrophotometry for monitoring the dose response characteristics of the hemoglobin molecule of irradiated blood. Blood samples were irradiated at doses ranging from 5 up to 100 Gy. Diluted hemoglobin solution was scanned in the UV- visible range (200-700 nm), and lyophilized hemoglobin was prepared for LAXS measurement. The radiation-induced changes in the hemoglobin structure have been evaluated. The LAXS profile of hemoglobin molecule is characterized by the presence of two peaks in the forward direction of scattering. These peaks were found to be sensitive to the variations in the molecular structure of a given sample. The obtained results suggest that the 1 s t peak, recorded at 4.65 o , is sensitive to the tertiary and quaternary structure of the globin part, while the major peak, recorded at 10.5 o , appeared to be related to its primary and secondary structure

21 CFR 522.1125 - Hemoglobin glutamer-200 (bovine).

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Hemoglobin glutamer-200 (bovine). 522.1125 Section... (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.1125 Hemoglobin glutamer-200 (bovine). (a) Specifications. Each 125 milliliter bag contains 13...

Expression of fully functional tetrameric human hemoglobin in Escherichia coli

International Nuclear Information System (INIS)

Hoffman, S.J.; Looker, D.L.; Roehrich, J.M.; Cozart, P.E.; Durfee, S.L.; Tedesco, J.L.; Stetler, G.L.

1990-01-01

Synthesis genes encoding the human α- and β-globin polypeptides have been expressed from a single operon in Escherichia coli. The α- and β-globin polypeptides associate into soluble tetramers, incorporate heme, and accumulate to >5% of the total cellular protein. Purified recombinant hemoglobin has the correct stoichiometry of α- and β-globin chains and contains a full complement of heme. Each globin chain also contains an additional methionine as an extension to the amino terminus. The recombinant hemoglobin has a C 4 reversed-phase HPLC profile essentially identical to that of human hemoglobin A 0 and comigrates with hemoglobin A 0 on SDS/PAGE. The visible spectrum and oxygen affinity are similar to that of native human hemoglobin A 0 . The authors have also expressed the α- and β-globin genes separately and found that the expression of the α-globin gene alone results in a marked decrease in the accumulation of α-globin in the cell. Separate expression of the β-globin gene results in high levels of insoluble β-globin. These observations suggest that the presence of α- and β-globin in the same cell stabilizes α-globin and aids the correct folding of β-globin. This system provides a simple method for expressing large quantities of recombinant hemoglobin and allows facile manipulation of the genes encoding hemoglobin to produce functionally altered forms of this protein

Propanil-induced methemoglobinemia and hemoglobin binding in the rat

Energy Technology Data Exchange (ETDEWEB)

McMillan, D.C.; McRae, T.A.; Hinson, J.A. (National Center for Toxicological Research, Jefferson, AR (USA))

1990-09-15

Administration of (ring-U-14C)propanil (3,4-dichloropropionanilide) to male Sprague-Dawley rats (30, 100, and 300 mg/kg, ip) increased the formation of methemoglobin at the two highest doses. Following a propanil dose of 100 mg/kg, methemoglobin formation attained a maximum level of 5% by 1.5 hr and declined to normal levels (approximately 2.5%) by 12 hr. Hemoglobin binding attained a maximum level of 50 pmol/mg protein by 12 hr, and remained constant for 24 hr. Following a propanil dose of 300 mg/kg, methemoglobin formation attained a maximum level of 24% by 4.5 hr, and declined to a level of 5% by 24 hr. Hemoglobin binding attained a maximum level of 425 pmol/mg protein by 12 hr, and remained constant for 24 hr. Hemoglobin binding was also detected at the lowest propanil dose (10 pmol/mg protein) even though methemoglobin formation was not observed. HPLC analysis of alkaline-treated hemoglobin from propanil-treated rats indicated the presence of one radiolabeled compound with the same HPLC retention time as 3,4-dichloraniline. These data are consistent with the concept that propanil is converted to N-hydroxy-3,4-dichloroaniline in the liver. Subsequently, this metabolite enters the erythrocyte and is oxidized by hemoglobin to 3,4-dichloronitrosobenzene with concomitant conversion of oxyhemoglobin to methemoglobin. The 3,4-dichloronitrosobenzene binds to cysteine residues on hemoglobin as the corresponding sulfinic acid amide adduct. These data suggest that human exposure to propanil may be monitored in the absence of observable toxicity by the analysis of propanil metabolites bound to hemoglobin.

Rice (Oryza) hemoglobins

Science.gov (United States)

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...

DAF in diabetic patients is subject to glycation/inactivation at its active site residues.

Science.gov (United States)

Flückiger, Rudolf; Cocuzzi, Enzo; Nagaraj, Ram H; Shoham, Menachem; Kern, Timothy S; Medof, M Edward

2018-01-01

Decay accelerating factor (DAF or CD55) is a cell associated C3 and C5 convertase regulator originally described in terms of protection of self-cells from systemic complement but now known to modulate adaptive T cell responses. It is expressed on all cell types. We investigated whether nonenzymatic glycation could impair its function and potentially be relevant to complications of diabetes mellitus and other conditions that result in nonenzymatic glycation including cancer, Alzheimer's disease, and aging. Immunoblots of affinity-purified DAF from erythrocytes of patients with diabetes showed pentosidine, glyoxal-AGEs, carboxymethyllysine, and argpyrimidine. HPLC/MS analyses of glucose modified DAF localized the sites of AGE modifications to K 125 adjacent to K 126 , K 127 at the junction of CCPs2-3 and spatially near R 96 , and R 100 , all identified as being critical for DAF's function. Functional analyses of glucose or ribose treated DAF protein showed profound loss of its regulatory activity. The data argue that de-regulated activation of systemic complement and de-regulated activation of T cells and leukocytes could result from non-enzymatic glycation of DAF. Copyright © 2017. Published by Elsevier Ltd.

Short-term effects of dietary advanced glycation end products in rats

DEFF Research Database (Denmark)

Poulsen, Malene Wibe; Andersen, Jeanette Marker; Hedegaard, Rikke Susanne Vingborg

2016-01-01

Dietary advanced glycation end products (AGE) formed during heating of food have gained interest as potential nutritional toxins with adverse effects on inflammation and glucose metabolism. In the present study, we investigated the short-term effects of high and low molecular weight (HMW and LMW)...

Evans Syndrome Complicated by Intratubular Hemoglobin Cast Nephropathy

Directory of Open Access Journals (Sweden)

Iván González

2017-01-01

Full Text Available Evans syndrome (ES is a rare autoimmune disorder whose exact pathophysiology is unknown. It is characterized by the simultaneous or subsequent development of autoimmune hemolytic anemia (AIHA and immune thrombocytopenia (ITP. Intravascular hemolysis, with hemoglobinemia, is known to produce acute kidney injury; however, the development of intratubular hemoglobin casts (hemoglobin cast nephropathy in the setting of acute hemolysis is uncommon. Likewise, the association of ES and acute renal failure is equally uncommon. We present a case of a 7-year-old girl with ES who developed acute kidney injury in the setting of intravascular hemolysis and had widespread intratubular hemoglobin casts.

21 CFR 864.7400 - Hemoglobin A2 assay.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Hemoglobin A2 assay. 864.7400 Section 864.7400 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Kits and Packages § 864.7400 Hemoglobin A2...

Action of carbon monoxide on the affinity of hemoglobin for oxygen

Energy Technology Data Exchange (ETDEWEB)

Vanuxem, D.; Weiller, P.J.; Guillot, C.; Grimaud, C.

1982-01-01

The authors have studied the action of carbon monoxide on the affinity of hemoglobin for oxygen by measuring P50 in whole blood and in stripped hemoglobin before and after exposition of blood samples from heavy smokers and polycythemic patients with high levels of HbCO to hyperbaric oxygen (2.2 ata). The concentration of 2,3-diphosphoglycerate was normal although P50 was significantly lowered, not only in whole blood but also in stripped hemoglobin. Hyperbaric oxygen normalized P50 by removing CO radicals from stripped hemoglobin. This may indicate that CO radicals exert a direct action on the hemoglobin molecule, at least at the HbCO levels studied in this work.

Nitrosyl hemoglobins: EPR above 80 K

Energy Technology Data Exchange (ETDEWEB)

Wajnberg, E.; Bemski, G.; El-Jaick, L.J.; Alves, O.C.

1995-03-01

The EPR spectra of nitrosyl hemoglobin and myoglobin in different conditions (native, denatured and lyophilized), as well as of hematin-NO were obtained in the temperature range of 80 K-280 K. There is a substantial and reversible.decrease of the areas of the EPR spectra of all the hemoglobin samples above 150 K. The interpretation of the results implies the existence of two conformational states in thermal equilibrium only one of which is EPR detectable. Thermodynamical parameters are determined for the hexa and penta-coordinated cases. (author). 25 refs, 3 figs.

Nitrosyl hemoglobins: EPR above 80 K

International Nuclear Information System (INIS)

Wajnberg, E.; Bemski, G.; El-Jaick, L.J.; Alves, O.C.

1995-03-01

The EPR spectra of nitrosyl hemoglobin and myoglobin in different conditions (native, denatured and lyophilized), as well as of hematin-NO were obtained in the temperature range of 80 K-280 K. There is a substantial and reversible.decrease of the areas of the EPR spectra of all the hemoglobin samples above 150 K. The interpretation of the results implies the existence of two conformational states in thermal equilibrium only one of which is EPR detectable. Thermodynamical parameters are determined for the hexa and penta-coordinated cases. (author). 25 refs, 3 figs

Generation of Soluble Advanced Glycation End Products Receptor (sRAGE)-Binding Ligands during Extensive Heat Treatment of Whey Protein/Lactose Mixtures Is Dependent on Glycation and Aggregation

NARCIS (Netherlands)

Liu, Fahui; Teodorowicz, Gosia; Wichers, Harry J.; Boekel, van Tiny; Hettinga, Kasper A.

2016-01-01

Heating of protein- and sugar-containing materials is considered the primary factor affecting the formation of advanced glycation end products (AGEs). This study aimed to investigate the influence of heating conditions, digestion, and aggregation on the binding capacity of AGEs to the soluble AGE

A spectroscopic study on the interaction between gold nanoparticles and hemoglobin

International Nuclear Information System (INIS)

Garabagiu, Sorina

2011-01-01

Highlights: ► The interaction was studied using UV–vis and fluorescence spectroscopy. ► Gold nanoparticles quench the fluorescence emission of hemoglobin solution. ► The binding and thermodynamic constants were calculated. ► Major impact: electrochemical applications of the complex onto a substrate. -- Abstract: The interaction between horse hemoglobin and gold nanoparticles was studied using optical spectroscopy. UV–vis and fluorescence spectra show that a spontaneous binding process occurred between hemoglobin and gold nanoparticles. The Soret band of hemoglobin in the presence of gold nanoparticles does not show significant changes, which proves that the protein retained its biological function. A shift to longer wavelengths appears in the plasmonic band of gold nanoparticles upon the attachment of hemoglobin molecules. Gold nanoparticles quench the fluorescence emission of tryptophan residues in the structure of hemoglobin. The Stern–Volmer quenching constant, the binding constant and the number of binding sites were also calculated. Thermodynamic parameters indicate that the binding was mainly due to hydrophobic interactions.

Human macrophage hemoglobin-iron metabolism in vitro

International Nuclear Information System (INIS)

Custer, G.; Balcerzak, S.; Rinehart, J.

1982-01-01

An entirely in vitro technique was employed to characterize hemoglobin-iron metabolism by human macrophages obtained by culture of blood monocytes and pulmonary alveolar macrophages. Macrophages phagocytized about three times as many erythrocytes as monocytes and six times as many erythrocytes as pulmonary alveolar macrophages. The rate of subsequent release of 59 Fe to the extracellular transferrin pool was two- to fourfold greater for macrophages as compared to the other two cell types. The kinetics of 59 Fe-transferrin release were characterized by a relatively rapid early phase (hours 1-4) followed by a slow phase (hours 4-72) for all three cell types. Intracellular movement of iron was characterized by a rapid shift from hemoglobin to ferritin that was complete with the onset of the slow phase of extracellular release. A transient increase in 59 Fe associated with an intracellular protein eluting with transferrin was also observed within 1 hour after phagocytosis. The process of hemoglobin-iron release to extracellular transferrin was inhibited at 4 degrees C but was unaffected by inhibitory of protein synthesis, glycolysis, microtubule function, and microfilament function. These data emphasize the rapidity of macrophage hemoglobin iron metabolism, provide a model for characterization of this process in vitro, and in general confirm data obtained utilizing in vivo animal models

Soluble Receptor for Advanced Glycation End Product: A Biomarker for Acute Coronary Syndrome

Directory of Open Access Journals (Sweden)

Louise J. N. Jensen

2015-01-01

Full Text Available The receptor of advanced glycation end products (RAGE and its ligands are linked to the pathogenesis of coronary artery disease (CAD, and circulating soluble receptor of advanced glycation end products (sRAGE, reflecting the RAGE activity, is suggested as a potential biomarker. Elevated sRAGE levels are reported in relation to acute ischemia and this review focuses on the role of sRAGE as a biomarker for the acute coronary syndrome (ACS. The current studies demonstrated that sRAGE levels are elevated in relation to ACS, however during a very narrow time period, indicating that the time of sampling needs attention. Interestingly, activation of RAGE may influence the pathogenesis and reflection in sRAGE levels in acute and stable CAD differently.

The Greenland shark Somniosus microcephalus-Hemoglobins and ligand-binding properties.

Directory of Open Access Journals (Sweden)

Roberta Russo

Full Text Available A large amount of data is currently available on the adaptive mechanisms of polar bony fish hemoglobins, but structural information on those of cartilaginous species is scarce. This study presents the first characterisation of the hemoglobin system of one of the longest-living vertebrate species (392 ± 120 years, the Arctic shark Somniosus microcephalus. Three major hemoglobins are found in its red blood cells and are made of two copies of the same α globin combined with two copies of three very similar β subunits. The three hemoglobins show very similar oxygenation and carbonylation properties, which are unaffected by urea, a very important compound in marine elasmobranch physiology. They display identical electronic absorption and resonance Raman spectra, indicating that their heme-pocket structures are identical or highly similar. The quaternary transition equilibrium between the relaxed (R and the tense (T states is more dependent on physiological allosteric effectors than in human hemoglobin, as also demonstrated in polar teleost hemoglobins. Similar to other cartilaginous fishes, we found no evidence for functional differentiation among the three isoforms. The very similar ligand-binding properties suggest that regulatory control of O2 transport may be at the cellular level and that it may involve changes in the cellular concentrations of allosteric effectors and/or variations of other systemic factors. The hemoglobins of this polar shark have evolved adaptive decreases in O2 affinity in comparison to temperate sharks.

Using the MWC model to describe heterotropic interactions in hemoglobin

Science.gov (United States)

Rapp, Olga

2017-01-01

Hemoglobin is a classical model allosteric protein. Research on hemoglobin parallels the development of key cooperativity and allostery concepts, such as the ‘all-or-none’ Hill formalism, the stepwise Adair binding formulation and the concerted Monod-Wymann-Changuex (MWC) allosteric model. While it is clear that the MWC model adequately describes the cooperative binding of oxygen to hemoglobin, rationalizing the effects of H+, CO2 or organophosphate ligands on hemoglobin-oxygen saturation using the same model remains controversial. According to the MWC model, allosteric ligands exert their effect on protein function by modulating the quaternary conformational transition of the protein. However, data fitting analysis of hemoglobin oxygen saturation curves in the presence or absence of inhibitory ligands persistently revealed effects on both relative oxygen affinity (c) and conformational changes (L), elementary MWC parameters. The recent realization that data fitting analysis using the traditional MWC model equation may not provide reliable estimates for L and c thus calls for a re-examination of previous data using alternative fitting strategies. In the current manuscript, we present two simple strategies for obtaining reliable estimates for MWC mechanistic parameters of hemoglobin steady-state saturation curves in cases of both evolutionary and physiological variations. Our results suggest that the simple MWC model provides a reasonable description that can also account for heterotropic interactions in hemoglobin. The results, moreover, offer a general roadmap for successful data fitting analysis using the MWC model. PMID:28793329

The impact of hemoglobin on the efficacy of phototherapy in hyperbilirubinemic infants

DEFF Research Database (Denmark)

Donneborg, Mette L; Vandborg, Pernille K; Hansen, Bo M

2017-01-01

BackgroundPhototherapy is the routine treatment for neonatal hyperbilirubinemia. Absorption of light in the skin transforms the native Z,Z-bilirubin to photobilirubins. This study investigates whether the hemoglobin concentration has an impact on efficacy of phototherapy, expressed by the decline...... decrease in TsB after 24 h was 121 (57-199) μmol/l; the median hemoglobin was 12.0 (7.0-14.7) mmol/l. There was a significant effect of hemoglobin concentration on the decrease in TsB of -3.61 μmol/mmol hemoglobin (P=0.022), after adjusting for initial TsB and postnatal age. That is, assuming the same...... initial TsB and postnatal age, for each mmol/l increase in hemoglobin, the decrease in TsB was 3.61 μmol/l smaller. In our hemoglobin range, the decrease in TsB is reduced by 28 μmol/l (23%).ConclusionIncreasing hemoglobin levels led to a decrease in the efficacy of phototherapy. Our data provide...

Comparative study of bedside and laboratory measurements of hemoglobin.

Science.gov (United States)

Krenzischek, D A; Tanseco, F V

1996-11-01

The purpose of this study was to examine the effects of variations in technique on measurements of hemoglobin level done at the bedside and to compare these results with laboratory measurements of hemoglobin. In accordance with hospital policy, procedure, and protocol, various techniques were used to obtain samples of capillary and venous blood and of blood from arterial and central venous catheters. Levels of hemoglobin were measured at the bedside and in the laboratory, and the results were compared. The Johns Hopkins Hospital adult postanesthesia care unit. A total of 187 blood samples were obtained from 62 adults who had undergone general surgery. Group I comprised 20 subjects with capillary and venous blood samples. Group II comprised 21 subjects with arterial blood samples. Group III comprised 21 subjects with central venous blood samples. The results showed that the amount of blood to be discarded before obtaining samples of arterial and central venous blood need not be any larger than double the dead space of the catheter, and that shaking the blood sample for 10 seconds was sufficient to mix the sample before measurement of hemoglobin levels. Results of bedside and laboratory measurements of hemoglobin level were comparable. Bedside measurement of hemoglobin increases efficiency in patient care, decreases risk of blood-transmitted infection for staff, and decreases cost to the patient. However, the persons who perform the assay must be responsible in adhering to the standard of practice to minimize errors in the measurements.

Prognostic value of hemoglobin concentration in radiotherapy for cancer of supraglottic larynx

International Nuclear Information System (INIS)

Tarnawski, Rafal; Skladowski, Krzysztof; Maciejewski, Boguslaw

1997-01-01

Purpose: The aim of this work is the estimation of correlations between hemoglobin concentration either before or after radiotherapy and local tumor control probability for laryngeal cancer. Methods and Materials: Retrospective analysis of 847 cases of laryngeal supraglottic squamous cell carcinoma treated with radiation alone was performed using maximum likelihood estimations, and step-wise logistic regression. All patients were in good initial performance status (Karnofsky index >70). The minimum follow-up time was 3 years. Results: Logistic regression showed that the hemoglobin concentration after radiotherapy is an important prognostic factor. There was a very strong correlation between hemoglobin concentration and tumor local control probability. Hemoglobin concentration at the beginning of radiotherapy does not correlate with treatment outcome, but any decrease of hemoglobin during therapy is a strong prognostic factor for treatment failure. Conclusions: Although regression models with many variables may be instable, the present results suggest that hemoglobin concentration after treatment is at least as important as overall treatment time. It was not possible to find out whether the low concentration of hemoglobin is an independent cause of low TCP or whether it reflects other mechanisms that may influence both hemoglobin level and the TCP

A nanocluster-based fluorescent sensor for sensitive hemoglobin detection.

Science.gov (United States)

Yang, Dongqin; Meng, Huijie; Tu, Yifeng; Yan, Jilin

2017-08-01

In this report, a fluorescence sensor for sensitive detection of hemoglobin was developed. Gold nanoclusters were first synthesized with bovine serum albumin. It was found that both hydrogen peroxide and hemoglobin could weakly quench the fluorescence from the gold nanoclusters, but when these two were applied onto the nanolcusters simultaneously, a much improved quenching was resulted. This enhancing effect was proved to come from the catalytic generation of hydroxyl radical by hemoglobin. Under an optimized condition, the quenching linearly related to the concentration of hemoglobin in the range of 1-250nM, and a limit of detection as low as 0.36nM could be obtained. This provided a sensitive means for the quantification of Hb. The sensor was then successfully applied for blood analyses with simple sample pretreatment. Copyright © 2017 Elsevier B.V. All rights reserved.

Temperature-dependent enthalpy of oxygenation in Antarctic fish hemoglobins

DEFF Research Database (Denmark)

Fago, A.; Wells, R.M.G.; Weber, Roy E.

1997-01-01

The effect of temperature on the oxygen-binding properties of the hemoglobins of three cold-adapted Antarctic fish species, Dissostichus mawsoni, Pagothenia borchgrevinki and Trematomus, sp., has been investigated under different pH values and buffer conditions. A clear non linear van't Hoff plot...... (logP(50) vs 1/T) of D. mawsoni hemoglobin indicates that the enthalpy of oxygenation (slope of the plot) is temperature dependent and that at high temperatures oxygen-binding becomes less exothermic. Nearly linear relationships were found in the hemoglobins of the other two species. The data were...... oxygen binding. The degree of the temperature dependence of the heat of oxygenation observed in these hemoglobins seems to reflect the differences in their allosteric effects rather than a specific molecular adaptation to low temperatures. Moreover, this study indicates that the disagreement between...

Hemoglobin Concentration and Risk of Incident Stroke in Community-Living Adults.

Science.gov (United States)

Panwar, Bhupesh; Judd, Suzanne E; Warnock, David G; McClellan, William M; Booth, John N; Muntner, Paul; Gutiérrez, Orlando M

2016-08-01

In previous observational studies, hemoglobin concentrations have been associated with an increased risk of stroke. However, these studies were limited by a relatively low number of stroke events, making it difficult to determine whether the association of hemoglobin and stroke differed by demographic or clinical factors. Using Cox proportional hazards analysis and Kaplan-Meier plots, we examined the association of baseline hemoglobin concentrations with incident stroke in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study, a cohort of black and white adults aged ≥45 years. A total of 518 participants developed stroke over a mean 7±2 years of follow-up. There was a statistically significant interaction between hemoglobin and sex (P=0.05) on the risk of incident stroke. In Cox regression models adjusted for demographic and clinical variables, there was no association of baseline hemoglobin concentration with incident stroke in men, whereas in women, the lowest (14.0 g/dL) quartiles of hemoglobin were associated with higher risk of stroke when compared with the second quartile (12.4-13.2 g/dL; quartile 1: hazard ratio, 1.59; 95% confidence interval, 1.09-2.31; quartile 2: referent; quartile 3: hazard ratio, 0.91; 95% confidence interval, 0.59-1.38; quartile 4: hazard ratio, 1.59; 95% confidence interval, 1.08-2.35). Similar results were observed in models stratified by hemoglobin and sex and when hemoglobin was modeled as a continuous variable using restricted quadratic spline regression. Lower and higher hemoglobin concentrations were associated with a higher risk of incident stroke in women. No such associations were found in men. © 2016 American Heart Association, Inc.

Nonenzymatic glycosylation of human hemoglobin at multiple sites

International Nuclear Information System (INIS)

Shapiro, R.; McManus, M.; Garrick, L.; McDonald, M.J.; Bunn, H.F.

1979-01-01

The most abundant minor hemoglobin component of human hemolysate is Hb A1c, which has glucose bound to the N-terminus of the beta chain by a ketoamine linkage. Hb A1c is formed slowly and continuously throughout the 120 day lifespan of the red cell. It can be synthesized in vitro by incubating purified hemoglobin with 14C-glucose. Other minor components, Hb A1a1 and Hb A1a2 are adducts of sugar phosphates at the N-terminus of the beta chain. Hb A1b contains an unidentified nonphosphorylated sugar at the beta N-terminus. In addition, a significant portion of the major hemoglobin component (Hb Ao) is also glycosylated by a glucose ketoamine linkage at other sites on the molecule, including the N-terminus of the alpha chain and the epsilon-amino group of several lysine residues on both the alpha and the beta chains. The results indicate that the interaction of glucose and hemoglobin is rather nonspecific and suggests that other proteins are modified in a similar fashion

Biophysical basis of hypoxic radioprotection by deoxygenated dextran-hemoglobin

International Nuclear Information System (INIS)

Wong, J.T.; Hill, R.P.

1986-01-01

Perfusion with deoxygenated dextran-hemoglobin provides an effective method for inducing hypoxic radioprotection of normal tissues during radiation treatment of tumors. In this study, the dependence of P50, the half-saturation pressure of oxygen binding to dextran-hemoglobin, was analyzed as a function of solution temperature and pH. The variation of attainable radioprotection with P50, and with the amount of collateral blood entering into the perfused region, was calculated. Upon perfusion of canine gracilis muscle with deoxygenated dextran-hemoglobin, a rapid onset of extensive venous hypoxia was observed

Histopathologic Study Following Administration of Liposome-Encapsulated Hemoglobin in the Normovolemic Rat

National Research Council Canada - National Science Library

Rudolph, Alan

1995-01-01

... bovine hemoglobin in the normovolemic rat. We have also examined the administration of the liposome vehicle, tetrameric bovine hemoglobin, and liposome encapsulated bovine hemoglobin that had been lyophilized with 300 mM trehalose...

Prior lactose glycation of caseinate via the Maillard reaction affects in vitro activities of the pepsin-trypsin digest toward intestinal epithelial cells.

Science.gov (United States)

Wang, X P; Zhao, X H

2017-07-01

The well-known Maillard reaction in milk occurs between lactose and milk proteins during thermal treatment, and its effects on milk nutrition and safety have been well studied. A lactose-glycated caseinate was prepared via this reaction and digested using 2 digestive proteases, pepsin and trypsin. The glycated caseinate digest was assessed for its in vitro activities on rat intestinal epithelial cells in terms of growth proliferation, anti-apoptotic effect, and differentiation induction using caseinate digest as reference, to verify potential effects of the Maillard reaction on these activities of caseinate digest to the cells. Two digests had proliferative and anti-apoptotic effects, and reached the highest effects at 0.02 g/L of digest concentration with treatment time of 24 h. In comparison with caseinate digest, glycated caseinate digest always showed weaker proliferative (5.3-14.2%) and anti-apoptotic (5.9-39.0%) effects, and was more toxic to the cells at 0.5 g/L of digest concentration with treatment time of 48 h. However, glycated caseinate digest at 2 incubation times of 4 to 7 d showed differentiation induction higher than caseinate digest, as it could confer the cells with increased activities in lactase (16.3-26.6%), sucrase (22.4-31.2%), and alkaline phosphatase (17.4-24.8%). Transmission electron microscopy observation results also confirmed higher differentiation induction of glycated caseinate digest. Amino acid loss and lactose glycation partially contributed to these decreased and enhanced activities of glycated caseinate digest, respectively. The Maillard reaction of caseinate and lactose is thus shown in this study to have effects on the activities of caseinate digest to intestinal epithelial cells. Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Structure and stability of human hemoglobin microparticles prepared with a double emulsion technique.

Science.gov (United States)

Cedrati, N; Bonneaux, F; Labrude, P; Maincent, P

1997-09-01

Hemoglobin solutions can be used as blood substitutes but they present some disadvantages often due to their rapid removal from the bloodstream after injection. A possible way of overcoming this problem is to trap hemoglobin inside particles. This study deals with the preparation, structure and stability of poly(lactic acid) and ethylcellulose microparticles containing human hemoglobin obtained with a double emulsion technique. We investigated the manufacturing process of these particles in order to increase the encapsulation ratio of hemoglobin. For this purpose, some parameters involved in the procedure were optimized, such as hemoglobin concentration and duration of stirring: hemoglobin loading increases with its concentration in the preparation and well-defined stirring time avoids a leakage of hemoglobin. Hemoglobin concentration, surfactant concentration i.e. poly(vinylic alcohol), amounts of polymer and solvent (methylene chloride), duration and speed of stirring. The microparticles were prepared with satisfactory yields (60 to 73%). They were spherical and their mean size was lower than 200 microns. The functional properties of entrapped hemoglobin were studied. The encapsulation did not alter hemoglobin and the oxygen affinity of the hemoglobin remained unmodified (P50 about 13.9 mm Hg in a Bis-Tris buffer pH 7.4 at 37 degrees C). Moreover, only low levels of methemoglobin could be detected (less than 3%). Besides, about 90% of encapsulated hemoglobin could be released from microparticles, with a speed related to the internal structure of the particles. The prepared microparticles were stored during one month at +4 degrees C. No degradation of the particle structure occurred and the functional properties of hemoglobin were preserved. These particles could provide a potential source of oxygen in the field of biotechnologies but any application for a transfusional purpose would first require a drastic reduction in particle size.

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African Journals Online (AJOL)

GB

2017-05-01

May 1, 2017 ... patient self-management education and support to prevent and ... Lifestyle changes such as nutrition therapy, weight loss ... Ethiopia. It plays an important role in teaching, ...... on Glycated hemoglobin and insulin sensitivity.

The mechanism of reduced IgG/IgE-binding of β-lactoglobulin by pulsed electric field pretreatment combined with glycation revealed by ECD/FTICR-MS.

Science.gov (United States)

Yang, Wenhua; Tu, Zongcai; Wang, Hui; Zhang, Lu; Kaltashov, Igor A; Zhao, Yunlong; Niu, Chendi; Yao, Honglin; Ye, Wenfeng

2018-01-24

Bovine β-lactoglobulin (β-Lg) is a major allergen existing in milk and causes about 90% of IgE-mediated cow's milk allergies. Previous studies showed that pulsed electric field (PEF) treatment could partially unfold the protein, which may contribute to the improvement of protein glycation. In this study, the effect of PEF pretreatment combined with glycation on the IgG/IgE-binding ability and the structure of β-Lg was investigated. The result showed that PEF pretreatment combined with glycation significantly reduced the IgG and IgE binding abilities, which was attributed to the changes of secondary and tertiary structure and the increase in glycation sites and degree of substitution per peptide (DSP) value determined by electron capture dissociation Fourier transform ion cyclotron resonance mass spectrometry (ECD/FTICR-MS). Unexpectedly, glycation sites (K47, K91 and K135) added by two mannose molecules were identified in glycated β-Lg with PEF pretreatment. Moreover, the results indicated that PEF pretreatment at 25 kV cm -1 for 60 μs promoted the reduction of IgG/IgE-binding capacity by increasing the glycation degree of β-Lg, whereas single PEF treatment under the same conditions markedly enhanced the IgG/IgE-binding ability by partially unfolding the structure of β-Lg. The results suggested that ECD/FTICR-MS could help us to understand the mechanism of reduction in the IgG/IgE-binding of β-Lg by structural characterization at the molecular level. Therefore, PEF pretreatment combined with glycation may provide an alternative method for β-Lg desensitization.

Effect of collagen turnover on the accumulation of advanced glycation end products

NARCIS (Netherlands)

Verzijl, N.; Degroot, J.; Thorpe, S. R.; Bank, R. A.; Shaw, J. N.; Lyons, T. J.; Bijlsma, J. W.; Lafeber, F. P.; Baynes, J. W.; TeKoppele, J. M.

2000-01-01

Collagen molecules in articular cartilage have an exceptionally long lifetime, which makes them susceptible to the accumulation of advanced glycation end products (AGEs). In fact, in comparison to other collagen-rich tissues, articular cartilage contains relatively high amounts of the AGE

[Hemoglobins, XXXII. Analysis of the primary structure of the monomeric hemoglobin CTT VIIA (erythrocruorin) or Chironomus thummi thummi, Diptera (author's transl)].

Science.gov (United States)

Kleinschmidt, T; Braunitzer, G

1980-01-01

The dimeric hemoglobin CTT VIIA (erythrocruorin) was isolated from the hemolymph of the larva from Chironomus thummi thummi and purified by preparative polyacrylamide gel electrophoresis. Peptides obtained by limited tryptical digestion were sequenced by automatic Edman degradation. For the elucidation of the sequence in the C-terminal region of the chain, additional cleavages with proteinase of Staphylococcus aureus and chymotrypsin were necessary. CTT VIIA is compared with human beta-chains and other hemoglobins of Chironomus. The amino acid residues in the pocket are especially discussed. Most of them are invariant in all Chironomus hemoglobins, independent of the size of the heme pocket, which is normal in some components and enlarged in others.

Cloned Hemoglobin Genes Enhance Growth Of Cells

Science.gov (United States)

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.

FRET imaging of hemoglobin concentration in Plasmodium falciparum-infected red cells.

Directory of Open Access Journals (Sweden)

Alessandro Esposito

Full Text Available During its intraerythrocytic asexual reproduction cycle Plasmodium falciparum consumes up to 80% of the host cell hemoglobin, in large excess over its metabolic needs. A model of the homeostasis of falciparum-infected red blood cells suggested an explanation based on the need to reduce the colloid-osmotic pressure within the host cell to prevent its premature lysis. Critical for this hypothesis was that the hemoglobin concentration within the host cell be progressively reduced from the trophozoite stage onwards.The experiments reported here were designed to test this hypothesis by direct measurements of the hemoglobin concentration in live, infected red cells. We developed a novel, non-invasive method to quantify the hemoglobin concentration in single cells, based on Förster resonance energy transfer between hemoglobin molecules and the fluorophore calcein. Fluorescence lifetime imaging allowed the quantitative mapping of the hemoglobin concentration within the cells. The average fluorescence lifetimes of uninfected cohorts was 270+/-30 ps (mean+/-SD; N = 45. In the cytoplasm of infected cells the fluorescence lifetime of calcein ranged from 290+/-20 ps for cells with ring stage parasites to 590+/-13 ps and 1050+/-60 ps for cells with young trophozoites and late stage trophozoite/early schizonts, respectively. This was equivalent to reductions in hemoglobin concentration spanning the range from 7.3 to 2.3 mM, in line with the model predictions. An unexpected ancillary finding was the existence of a microdomain under the host cell membrane with reduced calcein quenching by hemoglobin in cells with mature trophozoite stage parasites.The results support the predictions of the colloid-osmotic hypothesis and provide a better understanding of the homeostasis of malaria-infected red cells. In addition, they revealed the existence of a distinct peripheral microdomain in the host cell with limited access to hemoglobin molecules indicating the

Quantifying risk of penile prosthesis infection with elevated glycosylated hemoglobin.

Science.gov (United States)

Wilson, S K; Carson, C C; Cleves, M A; Delk, J R

1998-05-01

Elevation of glycosylated hemoglobin above levels of 11.5 mg.% has been considered a contraindication to penile prosthesis implantation in diabetic patients. We determine the predictive value of glycosylated hemoglobin A1C in penile prosthesis infections in diabetic and nondiabetic patients to confirm or deny this prevalent opinion. We conducted a 2-year prospective study of 389 patients, including 114 diabetics, who underwent 3-piece penile prosthesis implantation. All patients had similar preoperative preparation without regard to diabetic status, control or glycosylated hemoglobin A1C level. Risk of infection was statistically analyzed for diabetics versus nondiabetics, glycosylated hemoglobin A1C values above and below 11.5 mg.%, insulin dependent versus oral medication diabetics, and fasting blood sugars above and below 180 mg.%. Prosthesis infections developed in 10 diabetics (8.7%) and 11 nondiabetics (4.0%). No increased infection rate was observed in diabetics with high fasting sugars or diabetics on insulin. There was no statistically significant increased infection risk with increased levels of glycosylated hemoglobin A1C among all patients or among only the diabetics. In fact, there was no meaningful difference in the median or mean level of glycosylated hemoglobin A1C in the infected and noninfected patients regardless of diabetes. Use of glycosylated hemoglobin A1C values to identify and exclude surgical candidates with increased risk of infections is not proved by this study. Elevation of fasting sugar or insulin dependence also does not increase risk of infection in diabetics undergoing prosthesis implantation.

Presumptive binge eating disorder in type 2 diabetes mellitus patients and its effect in metabolic control

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Sandra Soares Melo

2009-09-01

Full Text Available Objective: This study sought to determine the presence of diagnosis suggestive of binge eating disorder in individuals with type 2 diabetes mellitus, and to evaluate the influence of such disorder on the metabolic control. Methods: sixty-three patients with type 2 diabetes mellitus and registered  at the Diabetes and Hypertension Program of a Health Unit in the town of Balneário Camboriú, Santa Catarina, Brazil, were evaluated. The diagnosis of binge eating disorder was made by analysis of the Questionnaire on Eating and Weight Patterms – Revised. For the evaluation of metabolic control, 10 ml of blood was collected, and the serum glucose, glycated hemoglobin, tryglicerides, cholestrol and fractions were determined. Weight and height were determined for evaluation of national nutritional state, according to the body mass index. Rresults: Among the evaluated individuals, 29% presented a diagnosis suggestive of binge eating disorder, with higher prevalence among females. The individuals with diagnosis suggestive of binge eating disorder presented a higher average body mass index value than the group without diagnosis. The serum concentrations of glycated hemoglobin (p = 0.02 and triglicerides (p = 0.03 were statistically higher in the group with diagnosis suggestive of binge eating disorder. Cconclusions: Based on the results of this study, it is possible to conclude that the presence of binge eating disorder in individuals with type 2 diabetes mellitus favors an increase in body weight and has a negative influence on metabolic control, contributing to the early emergence of complications related to the disease.

Hemoglobin Q-Thailand and its combinations with other forms of thalassemia or hemoglobinopathies in northern Thailand.

Science.gov (United States)

Panyasai, Sitthichai; Pornprasert, Sakorn

2014-01-01

There have been no reports for the frequency of Hb Q-Thailand [alpha 74(EF3)Asp --> His, GAC > CAC] and its combinations either with other forms of thalassemia or hemoglobinopathies in Northern Thailand. The aims of this study were to search for Hb Q-Thailand and its combinations in Northern Thai population and to analyze fractions of hemoglobin in Hb Q-Thailand and its combinations on high performance liquid chromatography (HPLC) chromatograms and/or capillary electrophoresis (CE) electrophoregrams. Blood samples from public and private hospitals in 7 northern provinces of Thailand were analyzed for thalassemia and hemoglobinopathy diagnoses using HPLC and/or CE and DNA analysis techniques at the Thalassemia Laboratory, Associated Medical Sciences Clinical Service Center, Chiang Mai, Thailand. Hb Q-Thailand was found in 13 of 13,596 (0.10%) samples; 6 were heterozygous Hb Q-Thailand, 4 were compound Hb Q-Thailand/alpha-thalassemia-1 Southeast Asian (SEA) type deletion and 3 with combinations of Hb Q-Thailand/beta(0)-thalassemia, Hb Q-Thailand/Hb E and Hb Q-Thailand/Hb E/alpha-thalassemia-1 SEA type deletion. The fractions of hemoglobin on HPLC chromatograms and CE electrophoregrams were observed based on types of combinations. Hb Q-Thailand and its combinations could be found in northern Thai population with the frequency of 0.10%. Thus, the better understanding of HPLC chromatogram and/or CE electrophoregram patterns of Hb Q-Thailand and its combination is essential for diagnosis and genetic counseling of thalassemia and hemoglobinopathies in this area.

PERBEDAAN KADAR HEMOGLOBIN METODE SIANMETHEMOGLOBIN DENGAN DAN TANPA SENTRIFUGASI PADA SAMPEL LEUKOSITOSIS

Directory of Open Access Journals (Sweden)

wahdah norsiah

2015-12-01

Full Text Available Abstract: Examination of hemoglobin levels influenced leukocytosis sianmethemoglobin method that causes increased absorbance measurements of hemoglobin levels increased significantly and the false blood sample that has been diluted with a solution Drabkins in centrifugation at 3000 rpm for 10 minutes and then the absorbance of the supernatant was measured with a photometer at λ 546 nm. This study aimed to analyze the differences in hemoglobin level examination siamethemoglobin method with and without centrifugation at sample leukocytosis. This type of research is observational research laboratory. The study design was cross-sectional study. Samples were taken from the remaining blood samples of patients who have been examined leukositnya number more than 20,000 / uL with Hematology Analyzer (CEL-DYN Ruby February-April 2014, and were divided into 4 groups based on criteria that group 1. leukocyte count of 20,000 / uL-29 999 / mL, group II. 30,000 / uL-39 999 / uL, the group III. 40,000 / uL-49,999 / uL, the group IV. More than 50,000 / uL. The number of samples taken were 20 samples of each group, a total sample of 80 samples. The analysis showed no significant difference in hemoglobin levels siamethemoglobin method with and without centrifugation at sample leukocytosis with a value of p = 0.000 less than 0.05 α. Leukocytosis Turbidity affects the difference in hemoglobin levels with and without centrifugation, the higher the number the greater the difference in leukocyte levels of hemoglobin, hemoglobin level examination results of the study based on the criteria of the number of leukocytes obtained by the difference in hemoglobin levels with and without centrifugation in group I. 0.22 ± 0.07 g / dL, group II 0.40 ± 0.22 g / dL, a group III. 0.44 ± 0.14 g / dL, Group IV. 0.85 ± 0.41 g / dL. The level of hemoglobin in the sample sianmethemoglobin method leukocytosis with more than 20,000 / uL need a centrifuge so that appropriate

[Hemoglobin variants in Colombian patients referred to discard hemoglobinopathies].

Science.gov (United States)

Romero-Sánchez, Consuelo; Gómez Gutiérrez, Alberto; Duarte, Yurani; Amazo, Constanza; Manosalva, Clara; Chila M, Lorena; Casas-Gómez, María Consuelo; Briceño Balcázar, Ignacio

2015-10-01

Oxygen transport is altered in hemoglobinopathies. To study the distribution of hemoglobinopathies in Andean subjects without African ancestry. We analyzed blood samples of 1,407 subjects aged 18 to 59 years (58% females), living in the central Andean region of Colombia, referred to discard hemoglobinopathies. The frequency and type of hemoglobinopathy was established by capillary and agarose gel electrophoresis. The frequency of hemoglobinopathies was 34.5% and higher among females. The structural variants found were: AS-heterozygous hemoglobin (8.1%), homozygous SS (3.7%), heterozygous SC (2.2%), AC heterozygotes (0.5%) and heterozygous AE (0.3%). Quantitative variants found were Hb A-Beta thalassemia (13.91%) and Hb H (0.06%), Beta-thalassemia heterozygotes C (0.88%), S-Beta thalassemia heterozygotes (6.07%) and compound heterozygous SC/Beta thalassemia (0.25%), with a persistence of fetal hemoglobin 0. Composite thalassemia was also found in 31%. All techniques showed good correlation and capillary electrophoresis demonstrated a greater detection of hemoglobin variants. The frequency of hemoglobin variants in the analyzed population was high, which is an important public health indicator. The most common hemoglobin variant was HbA/Increased structural Hb A2 and the mos frequent structural hemoglobinopathy was sickle cell trait. Capillary electrophoresis can discern any Hb variants present in the population.

Study of LAXS Profile of Hemoglobin from Irradiated Blood

International Nuclear Information System (INIS)

Selim, N.S.; Desouky, O.S.; Elshemey, W.M.

2006-01-01

The present work aims to move a step forward towards a deeper understanding of the scattering of x-ray, from lyophilized biological samples. Comparative study has been performed using low angle x-ray scattering (LAXS) and UV-visible spectrophotometry for monitoring the dose response characteristics of the hemoglobin molecule of irradiated blood. Blood samples were exposed to gamma rays, at doses ranging from 5 up to 100 Gy. Diluted hemoglobin solution was scanned in the UV-visible range (200-700 nm), and lyophilized hemoglobin was prepared for LAXS measurement. The radiation-induced changes in the hemoglobin structure have been evaluated. The LAXS profile of hemoglobin molecule is characterized by the presence of 2 peaks in the forward direction of scattering. These peaks were found to be sensitive to the variations in the molecular structure of a given sample. The obtained results suggest that the 1st peak, recorded at 4.65O (equivalent to momentum transfer, x= 0.526 nm-1), is sensitive to the tertiary and quaternary structure of the globin part, while the major peak, recorded at 10.5O (equivalent to momentum transfer, x= 1.189 nm-1), appeared to be related to its primary and secondary structure

Is a blood sample for hemoglobins in the transfusional range reliable?

Science.gov (United States)

López, A; Gómez, L; Petinal, G; Adán, N; Alvarado, S; Carballo, N

2018-02-27

To evaluate the correlation and agreement in our unit and population of hemoglobin in gasometry versus hematology analyzer, to evaluate errors in transfusion or lack thereof. strong association between Point-of-care (POC) and hematimetry, with P<.001, with a coefficient of determination r 2 of 0.56, an intraclass correlation coefficient of 0.63 and a Lin's concordance correlation coefficient of 0.65. For hemoglobins less than 7g/dL, a success rate of 29.41% was obtained. Low-moderate agreement of POC hemoglobin with standard haemothymetry. High probability of errors in the indication of transfusion based on gasometer hemoglobins, especially in low hemoglobins. Copyright © 2018 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.

Hemoglobin Levels Across the Pediatric Critical Care Spectrum: A Point Prevalence Study.

Science.gov (United States)

Hassan, Nabil E; Reischman, Diann E; Fitzgerald, Robert K; Faustino, Edward Vincent S

2018-05-01

To determine the prevailing hemoglobin levels in PICU patients, and any potential correlates. Post hoc analysis of prospective multicenter observational data. Fifty-nine PICUs in seven countries. PICU patients on four specific days in 2012. None. Patients' hemoglobin and other clinical and institutional data. Two thousand three hundred eighty-nine patients with median age of 1.9 years (interquartile range, 0.3-9.8 yr), weight 11.5 kg (interquartile range, 5.4-29.6 kg), and preceding PICU stay of 4.0 days (interquartile range, 1.0-13.0 d). Their median hemoglobin was 11.0 g/dL (interquartile range, 9.6-12.5 g/dL). The prevalence of transfusion in the 24 hours preceding data collection was 14.2%. Neonates had the highest hemoglobin at 13.1 g/dL (interquartile range, 11.2-15.0 g/dL) compared with other age groups (p < 0.001). The percentage of 31.3 of the patients had hemoglobin of greater than or equal to 12 g/dL, and 1.1% had hemoglobin of less than 7 g/dL. Blacks had lower median hemoglobin (10.5; interquartile range, 9.3-12.1 g/dL) compared with whites (median, 11.1; interquartile range, 9.0-12.6; p < 0.001). Patients in Spain and Portugal had the highest median hemoglobin (11.4; interquartile range, 10.0-12.6) compared with other regions outside of the United States (p < 0.001), and the highest proportion (31.3%) of transfused patients compared with all regions (p < 0.001). Patients in cardiac PICUs had higher median hemoglobin than those in mixed PICUs or noncardiac PICUs (12.3, 11.0, and 10.6 g/dL, respectively; p < 0.001). Cyanotic heart disease patients had the highest median hemoglobin (12.6 g/dL; interquartile range, 11.1-14.5). Multivariable regression analysis within diagnosis groups revealed that hemoglobin levels were significantly associated with the geographic location and history of complex cardiac disease in most of the models. In children with cancer, none of the variables tested correlated with patients' hemoglobin levels

A Perspective on the Maillard Reaction and the Analysis of Protein Glycation by Mass Spectrometry: Probing the Pathogenesis of Chronic Disease

Energy Technology Data Exchange (ETDEWEB)

Zhang, Qibin; Ames, Jennifer M.; Smith, Richard D.; Baynes, John; Metz, Thomas O.

2008-12-18

The Maillard reaction, starting from the glycation of protein and progressing to the formation of advanced glycation end-products (AGEs), is implicated in the development of complications of diabetes mellitus, as well as in the pathogenesis of cardiovascular, renal, and neurodegenerative diseases. In this perspective review, we provide on overview on the relevance of the Maillard reaction in the pathogenesis of chronic disease and discuss traditional approaches and recent developments in the analysis of glycated proteins by mass spectrometry. We propose that proteomics approaches, particularly bottom-up proteomics, will play a significant role in analyses of clinical samples leading to the identification of new markers of disease development and progression.

A perspective on the Maillard reaction and the analysis of protein glycation by mass spectrometry: probing the pathogenesis of chronic disease.

Science.gov (United States)

Zhang, Qibin; Ames, Jennifer M; Smith, Richard D; Baynes, John W; Metz, Thomas O

2009-02-01

The Maillard reaction, starting from the glycation of protein and progressing to the formation of advanced glycation end-products (AGEs), is implicated in the development of complications of diabetes mellitus, as well as in the pathogenesis of cardiovascular, renal, and neurodegenerative diseases. In this perspective review, we provide an overview on the relevance of the Maillard reaction in the pathogenesis of chronic disease and discuss traditional approaches and recent developments in the analysis of glycated proteins by mass spectrometry. We propose that proteomics approaches, particularly bottom-up proteomics, will play a significant role in analyses of clinical samples leading to the identification of new markers of disease development and progression.

(R)-α-Lipoic acid inhibits fructose-induced myoglobin fructation and the formation of advanced glycation end products (AGEs) in vitro.

Science.gov (United States)

Ghelani, Hardik; Razmovski-Naumovski, Valentina; Pragada, Rajeswara Rao; Nammi, Srinivas

2018-01-15

Fructose-mediated protein glycation (fructation) has been linked to an increase in diabetic and cardiovascular complications due to over consumption of high-fructose containing diets in recent times. The objective of the present study is to evaluate the protective effect of (R)-α-lipoic acid (ALA) against fructose-induced myoglobin fructation and the formation of advanced glycation end products (AGEs) in vitro. The anti-glycation activity of ALA was determined using the formation of AGEs fluorescence intensity, iron released from the heme moiety of myoglobin and the level of fructosamine. The fructation-induced myoglobin oxidation was examined using the level of protein carbonyl content and thiol group estimation. The results showed that co-incubation of myoglobin (1 mg/mL), fructose (1 M) and ALA (1, 2 and 4 mM) significantly inhibited the formation of AGEs during the 30 day study period. ALA markedly decreased the levels of fructosamine, which is directly associated with the reduction of AGEs formation. Furthermore, ALA significantly reduced free iron release from myoglobin which is attributed to the protection of myoglobin from fructose-induced glycation. The results also demonstrated a significant protective effect of ALA on myoglobin oxidative damages, as seen from decreased protein carbonyl content and increased protein thiols. These findings provide new insights into the anti-glycation properties of ALA and emphasize that ALA supplementation is beneficial in the prevention of AGEs-mediated diabetic and cardiovascular complications.

Point-of-care hemoglobin testing for postmortem diagnosis of anemia.

Science.gov (United States)

Na, Joo-Young; Park, Ji Hye; Choi, Byung Ha; Kim, Hyung-Seok; Park, Jong-Tae

2018-03-01

An autopsy involves examination of a body using invasive methods such as dissection, and includes various tests using samples procured during dissection. During medicolegal autopsies, the blood carboxyhemoglobin concentration is commonly measured using the AVOXimeter® 4000 as a point-of-care test. When evaluating the body following hypovolemic shock, characteristics such as reduced livor mortis or an anemic appearance of the viscera can be identified, but these observations arequite subjective. Thus, a more objective test is required for the postmortem diagnosis of anemia. In the present study, the AVOXimeter® 4000 was used to investigate the utility of point-of-care hemoglobin testing. Hemoglobin tests were performed in 93 autopsy cases. The AVOXimeter® 4000 and the BC-2800 Auto Hematology Analyzer were used to test identical samples in 29 of these cases. The results of hemoglobin tests performed with these two devices were statistically similar (r = 0.969). The results of hemoglobin tests using postmortem blood were compared with antemortem test results from medical records from 31 cases, and these results were similar. In 13 of 17 cases of death from internal hemorrhage, hemoglobin levels were lower in the cardiac blood than in blood from the affected body cavity, likely due to compensatory changes induced by antemortem hemorrhage. It is concluded that blood hemoglobin testing may be useful as a point-of-care test for diagnosing postmortem anemia.

Enhancement of Salinity Tolerance during Rice Seed Germination by Presoaking with Hemoglobin

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Sheng Xu

2011-04-01

Full Text Available Salinity stress is an important environmental constraint limiting the productivity of many crops worldwide. In this report, experiments were conducted to investigate the effects of seed presoaking by bovine hemoglobin, an inducer of heme oxygenase-1 (HO-1, on salinity tolerance in rice (Oryza sativa plants. The results showed that different concentrations of the hemoglobin (0.01, 0.05, 0.2, 1.0, and 5.0 g/L differentially alleviated the inhibition of rice seed germination and thereafter seedling shoot growth caused by 100 mM NaCl stress, and the responses of 1.0 g/L hemoglobin was the most obvious. Further analyses showed that application of hemoglobin not only increased the HO-1 gene expression, but also differentially induced catalase (CAT, ascorbate peroxidase (APX, and superoxide dismutase (SOD activities or transcripts, thus decreasing the lipid peroxidation in germinating rice seeds subjected to salt stress. Compared with non-hemoglobin treatment, hemoglobin presoaking also increased the potassium (K to sodium (Na ratio both in the root and shoot parts after salinity stress. The effect is specific for HO-1 since the potent HO-1 inhibitor zinc protoporphyrin IX (ZnPPIX blocked the positive actions of hemoglobin on seed germination and seedling shoot growth. Overall, these results suggested that hemoglobin performs an advantageous role in enhancement of salinity tolerance during rice seed germination.

Advanced glycation end-products (AGES) and heart failure : Pathophysiology and clinical implications

NARCIS (Netherlands)

Hartog, Jasper W. L.; Voors, Adriaan A.; Bakker, Stephan J. L.; Smit, Andries J.; van Veldhuisen, Dirk J.

2007-01-01

Advanced glycation end-products (AGEs) are molecules formed during a non-enzymatic reaction between proteins and sugar residues, called the Maillard reaction. AGEs accumulate in the human body with age, and accumulation is accelerated in the presence of diabetes mellitus. In patients with diabetes,

Structural and functional properties of hemoglobins from unicellular organisms as revealed by resonance Raman spectroscopy.

Science.gov (United States)

Egawa, Tsuyoshi; Yeh, Syun-Ru

2005-01-01

Hemoglobins have been discovered in organisms from virtually all kingdoms. Their presence in unicellular organisms suggests that the gene for hemoglobin is very ancient and that the hemoglobins must have functions other than oxygen transport, in view of the fact that O2 delivery is a diffusion-controlled process in these organisms. Based on sequence alignment, three groups of hemoglobins have been characterized in unicellular organisms. The group-one hemoglobins, termed truncated hemoglobins, consist of proteins with 110-140 amino acid residues and a novel two-over-two alpha-helical sandwich motif. The group-two hemoglobins, termed flavohemoglobins, consist of a hemoglobin domain, with a classical three-over-three alpha-helical sandwich motif, and a flavin-containing reductase domain that is covalently attached to it. The group-three hemoglobins consist of myoglobin-like proteins that have high sequence homology and structural similarity to the hemoglobin domain of flavohemoglobins. In this review, recent resonance Raman studies of each group of these proteins are presented. Their implications are discussed in the context of the structural and functional properties of these novel hemoglobins.

Hemoglobin Rahere, a human hemoglobin variant with amino acid substitution at the 2,3-diphosphoglycerate binding site. Functional consequences of the alteration and effects of bezafibrate on the oxygen bindings.

Science.gov (United States)

Sugihara, J; Imamura, T; Nagafuchi, S; Bonaventura, J; Bonaventura, C; Cashon, R

1985-09-01

We encountered an abnormal hemoglobin (Rahere), with a threonine residue replacing the beta 82 (EF6) lysine residue at the binding site of 2,3-diphosphoglycerate, which was responsible for overt erythrocytosis in two individuals of a Japanese family. Hemoglobin Rahere shows a lower oxygen affinity on the binding of 2,3-diphosphoglycerate or chloride ions than hemoglobin A. Although a decrease in the positive charge density at the binding sites of 2,3-diphosphoglycerate in hemoglobin Rahere apparently shifts the allosteric equilibrium toward the low affinity state, it greatly diminishes the cofactor effects by anions. The oxygen affinity of the patient's erythrocytes is substantially lowered by the presence of bezafibrate, which combines with sites different from those of 2,3-diphosphoglycerate in either hemoglobin Rahere or hemoglobin A.

Calorimetric and spectroscopic properties of small globular proteins (bovine serum albumin, hemoglobin) after free radical generation

International Nuclear Information System (INIS)

Farkas, N.; Belagyi, J.; Lorinczy, D.

2003-01-01

Mild oxidation of -SH-containing proteins (serum albumin, hemoglobin) by Ce(IV)-ions in the presence of the spin trap phenyl-tert-butylnitrone (PBN) resulted in the appearance of strongly immobilized nitroxide free radicals which evidences the formation of thiyl radicals on the thiol site of the proteins. In hydroxyl free radical generating system a fraction of strongly immobilized nitroxide radicals was also detected in these proteins, which implies that the oxidation of a fraction of the thiol groups was also involved in the free radical reaction. According to the differential scanning calorimetry (DSC) experiments the melting processes of the proteins were calorimetrically irreversible, therefore the two-state kinetic model was used to evaluate the experiments. The results support the view that site-specific interaction of SH-containing proteins with hydroxyl and thiyl free radicals is able to modify the internal dynamics of proteins and affect the conformation of large molecules

Novel subunit structure observed for noncooperative hemoglobin from Urechis caupo.

Science.gov (United States)

Kolatkar, P R; Meador, W E; Stanfield, R L; Hackert, M L

1988-03-05

Tetrameric hemoglobin from the "fat innkeeper" worm Urechis caupo possesses a novel subunit arrangement having an "inside out" quaternary structure in that the G/H helices are located on the outer surface of the tetramer. A 5-A resolution crystal structure reveals that although the individual subunits are beta-like, having a distinct D helix and the general myoglobin fold, the subunit contacts are very different from those previously observed for hemoglobins. Furthermore, the hemoglobin from U. caupo is also quite different from the unusual hemoglobin tetramer from clam which also has its G/H helices on the outer surface but with the hemes in close proximity through E-F helical contacts (Royer, W. E., Jr., Love, W. E., and Fenderson, F. F. (1985) Nature 316, 277-280).

Hemoglobin as a factor in the control of tumor oxygenation

International Nuclear Information System (INIS)

Hirst, D.G.

1987-01-01

The concentration of hemoglobin in the blood has been shown to have a market effect on the radiosensitivity of human and animal tumors. Experimental studies in mice indicate that radiosensitivity is influenced by a change in the hemoglobin level rather than by the absolute concentration. This dependence may be exploited to therapeutic advantage. Recent studies of hemoglobin/oxygen affinity have shown that the concentration of 2,3 diphosphoglycerate (2,3 DPG) affects tumor sensitivity to X-rays. Increased 2,3 DPG levels increase radiosensitivity in several mouse tumors. The time dependence of this effect remains to be established. The effective application of these effects in man may depend on the development of drugs which produce changes in hemoglobin affinity without the need for blood transfusions. Several drugs are currently being investigated

Effect of dietary advanced glycation end products on postprandial appetite, inflammation, and endothelial activation in healthy overweight individuals

DEFF Research Database (Denmark)

Poulsen, Malene Wibe; Bak, Monika Judyta; Andersen, Jeanette Marker

2014-01-01

Advanced glycation end products (AGEs) formed in food during high-heat cooking may induce overeating and inflammation. We investigated whether AGE contents in a single meal affect postprandial appetite and markers of inflammation, endothelial activation, and oxidative stress.......Advanced glycation end products (AGEs) formed in food during high-heat cooking may induce overeating and inflammation. We investigated whether AGE contents in a single meal affect postprandial appetite and markers of inflammation, endothelial activation, and oxidative stress....

Site-specific semisynthetic variant of human hemoglobin

International Nuclear Information System (INIS)

Hefta, S.A.; Lyle, S.B.; Busch, M.R.; Harris, D.E.; Matthew, J.B.; Gurd, F.R.N.

1988-01-01

A single round of Edman degradation was employed to remove the NH 2 -terminal valine from isolated α chains of human hemoglobin. Reconstitution of normal β chains with truncated or substituted α chains was used to form truncated (des-Val 1 -α1) and substituted ([[1- 13 C]Gly 1 ]α1) tetrameric hemoglobin analogs. Structural homology of the analogs with untreated native hemoglobin was established by using several spectroscopic and physical methods. Functional studies indicate that the reconstituted tetrameric protein containing des-Val 1 -α chains has a higher affinity for oxygen, is less influenced by chloride ions or 2,3-biphosphoglycerate, and shows lower cooperativity than native hemoglobin. These results confirm the key functional role of the α-chain NH 2 terminus in mediating cooperative oxygen binding across the dimer interface. The NH 2 -terminal pK/sub 1/2/ value was determined for the [ 13 C]glycine-substituted analog to be 7.46 +/- 0.09 at 15 0 C in the carbon monoxide-liganded form. This value, measured directly by 13 C NMR, agrees with the determination made by the less-direct 13 CO 2 method and confirms the role of this residue as a contributor to the alkaline Bohr effect; however, it is consistent with the presence of an NH 2 -terminal salt bridge to the carboxylate of Arg-141 of the α chain in the liganded form

Improvements in or relating to antibodies active against human hemoglobin Asub(1C)

International Nuclear Information System (INIS)

Javid, J.; Cerami, A.; Koenig, R.J.; Pettis, P.K.

1980-01-01

A method is described for preparing an antibody against human hemoglobin Asub(1c) which is substantially free of cross-reactivity against the human hemoglobins A 0 , Asub(1a) and Asub(1b). The antibodies are collected from cats, goats or sheep following injections of purified hemoglobin Asub(1c) antigen since these animals do not naturally produce hemoglobin Asub(1c). A radioimmunoassay method is also described whereby these antibodies are used to determine the quantity of hemoglobin Asub(1c) in blood samples. This is a useful technique in the diagnosis of diabetes mellitus. (U.K.)

Further studies on Hb Canebière [β12(G4)Asn→His], a low affinity hemoglobin variant

DEFF Research Database (Denmark)

Froelund, Ulf; Sandbakken, Erik; Szecsi, Pal Bela

2010-01-01

A case of Hb Canebière [ß102(G4)Asn¿His] was diagnosed in an otherwise healthy 21-year-old Danish woman. The clinical consequences were minor, since her only symptom consisted of transient cyanosis in lips and fingers when exposed to cold environments. Whole blood p50 was 59.9 mmHg. The Hb Canebi...... Canebière variant could not be separated from Hb A by high performance liquid chromatography (HPLC) and isoelectric focusing (IEF), and it was thus missed by routine hemoglobin (Hb) fractionation techniques....

Further studies on Hb Canebière [β12(G4)Asn→His], a low affinity hemoglobin variant

DEFF Research Database (Denmark)

Froelund, Ulf; Sandbakken, Erik; Szecsi, Pal Bela

2010-01-01

A case of Hb Canebière [β102(G4)Asn→His] was diagnosed in an otherwise healthy 21-year-old Danish woman. The clinical consequences were minor, since her only symptom consisted of transient cyanosis in lips and fingers when exposed to cold environments. Whole blood p50 was 59.9 mmHg. The Hb...... Canebière variant could not be separated from Hb A by high performance liquid chromatography (HPLC) and isoelectric focusing (IEF), and it was thus missed by routine hemoglobin (Hb) fractionation techniques....

Lower versus Higher Hemoglobin Threshold for Transfusion in Septic Shock

DEFF Research Database (Denmark)

Holst, Lars B; Haase, Nicolai; Wetterslev, Jørn

2014-01-01

BACKGROUND: Blood transfusions are frequently given to patients with septic shock. However, the benefits and harms of different hemoglobin thresholds for transfusion have not been established. METHODS: In this multicenter, parallel-group trial, we randomly assigned patients in the intensive care...... unit (ICU) who had septic shock and a hemoglobin concentration of 9 g per deciliter or less to receive 1 unit of leukoreduced red cells when the hemoglobin level was 7 g per deciliter or less (lower threshold) or when the level was 9 g per deciliter or less (higher threshold) during the ICU stay...... were similar in the two intervention groups. CONCLUSIONS: Among patients with septic shock, mortality at 90 days and rates of ischemic events and use of life support were similar among those assigned to blood transfusion at a higher hemoglobin threshold and those assigned to blood transfusion...

Hemoglobin Rahere, a human hemoglobin variant with amino acid substitution at the 2,3-diphosphoglycerate binding site. Functional consequences of the alteration and effects of bezafibrate on the oxygen bindings.

OpenAIRE

Sugihara, J; Imamura, T; Nagafuchi, S; Bonaventura, J; Bonaventura, C; Cashon, R

1985-01-01

We encountered an abnormal hemoglobin (Rahere), with a threonine residue replacing the beta 82 (EF6) lysine residue at the binding site of 2,3-diphosphoglycerate, which was responsible for overt erythrocytosis in two individuals of a Japanese family. Hemoglobin Rahere shows a lower oxygen affinity on the binding of 2,3-diphosphoglycerate or chloride ions than hemoglobin A. Although a decrease in the positive charge density at the binding sites of 2,3-diphosphoglycerate in hemoglobin Rahere ap...

The Receptor for Advanced Glycation End Products Impairs Host Defense in Pneumococcal Pneumonia

NARCIS (Netherlands)

van Zoelen, Marieke A. D.; Schouten, Marcel; de Vos, Alex F.; Florquin, Sandrine; Meijers, Joost C. M.; Nawroth, Peter P.; Bierhaus, Angelika; van der Poll, Tom

2009-01-01

Streptococcus pneumoniae is the most common cause of community-acquired pneumonia. The receptor for advanced glycation end products (RAGE) is a multiligand receptor that is expressed ubiquitously in the lungs. Engagement of RAGE leads to activation of multiple intracellular signaling pathways,

Influence of hemoglobin on non-invasive optical bilirubin sensing

Science.gov (United States)

Jiang, Jingying; Gong, Qiliang; Zou, Da; Xu, Kexin

2012-03-01

Since the abnormal metabolism of bilirubin could lead to diseases in the human body, especially the jaundice which is harmful to neonates. Traditional invasive measurements are difficult to be accepted by people because of pain and infection. Therefore, the real-time and non-invasive measurement of bilirubin is of great significance. However, the accuracy of currently transcutaneous bilirubinometry(TcB) is generally not high enough, and affected by many factors in the human skin, mostly by hemoglobin. In this talk, absorption spectra of hemoglobin and bilirubin have been collected and analyzed, then the Partial Least Squares (PLS) models have been built. By analyzing and comparing the Correlation and Root Mean Square Error of Prediction(RMSEP), the results show that the Correlation of bilirubin solution model is larger than that of the mixture solution added with hemoglobin, and its RMSEP value is smaller than that of mixture solution. Therefore, hemoglobin has influences on the non-invasive optical bilirubin sensing. In next step, it is necessary to investigate how to eliminate the influence.

Hemoglobin levels and new-onset heart failure in the community

NARCIS (Netherlands)

Klip, IJsbrand T.; Postmus, Douwe; Voors, Adriaan A.; Brouwers, Frank P. J.; Gansevoort, Ron T.; Bakker, Stephan J. L.; Hillege, Hans L.; de Boer, Rudolf A.; van der Harst, Pim; van Gilst, Wiek H.; van Veldhuisen, Dirk J.; van der Meer, Peter

Background In established cardiovascular disease and heart failure (HF), low hemoglobin levels are associated with unfavorable outcome. Whether hemoglobin levels are associated with the development of new-onset HF in the population is unclear. This study sought to investigate the relationship

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

Science.gov (United States)

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

2018-01-01

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

Modeling hemoglobin at optical frequency using the unconditionally stable fundamental ADI-FDTD method.

Science.gov (United States)

Heh, Ding Yu; Tan, Eng Leong

2011-04-12

This paper presents the modeling of hemoglobin at optical frequency (250 nm - 1000 nm) using the unconditionally stable fundamental alternating-direction-implicit finite-difference time-domain (FADI-FDTD) method. An accurate model based on complex conjugate pole-residue pairs is proposed to model the complex permittivity of hemoglobin at optical frequency. Two hemoglobin concentrations at 15 g/dL and 33 g/dL are considered. The model is then incorporated into the FADI-FDTD method for solving electromagnetic problems involving interaction of light with hemoglobin. The computation of transmission and reflection coefficients of a half space hemoglobin medium using the FADI-FDTD validates the accuracy of our model and method. The specific absorption rate (SAR) distribution of human capillary at optical frequency is also shown. While maintaining accuracy, the unconditionally stable FADI-FDTD method exhibits high efficiency in modeling hemoglobin.

Rifampicin reduces advanced glycation end products and activates DAF-16 to increase lifespan in Caenorhabditis elegans.

Science.gov (United States)

Golegaonkar, Sandeep; Tabrez, Syed S; Pandit, Awadhesh; Sethurathinam, Shalini; Jagadeeshaprasad, Mashanipalya G; Bansode, Sneha; Sampathkumar, Srinivasa-Gopalan; Kulkarni, Mahesh J; Mukhopadhyay, Arnab

2015-06-01

Advanced glycation end products (AGEs) are formed when glucose reacts nonenzymatically with proteins; these modifications are implicated in aging and pathogenesis of many age-related diseases including type II diabetes, atherosclerosis, and neurodegenerative disorders. Thus, pharmaceutical interventions that can reduce AGEs may delay age-onset diseases and extend lifespan. Using LC-MS(E), we show that rifampicin (RIF) reduces glycation of important cellular proteins in vivo and consequently increases lifespan in Caenorhabditis elegans by up to 60%. RIF analog rifamycin SV (RSV) possesses similar properties, while rifaximin (RMN) lacks antiglycation activity and therefore fails to affect lifespan positively. The efficacy of RIF and RSV as potent antiglycating agents may be attributed to the presence of a p-dihydroxyl moiety that can potentially undergo spontaneous oxidation to yield highly reactive p-quinone structures, a feature absent in RMN. We also show that supplementing rifampicin late in adulthood is sufficient to increase lifespan. For its effect on longevity, rifampicin requires DAF-18 (nematode PTEN) as well as JNK-1 and activates DAF-16, the FOXO homolog. Interestingly, the drug treatment modulates transcription of a different subset of DAF-16 target genes, those not controlled by the conserved Insulin-IGF-1-like signaling pathway. RIF failed to increase the lifespan of daf-16 null mutant despite reducing glycation, showing thereby that DAF-16 may not directly affect AGE formation. Together, our data suggest that the dual ability to reduce glycation in vivo and activate prolongevity processes through DAF-16 makes RIF and RSV effective lifespan-extending interventions. © 2015 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Optical wavelength selection for portable hemoglobin determination by near-infrared spectroscopy method

Science.gov (United States)

Tian, Han; Li, Ming; Wang, Yue; Sheng, Dinggao; Liu, Jun; Zhang, Linna

2017-11-01

Hemoglobin concentration is commonly used in clinical medicine to diagnose anemia, identify bleeding, and manage red blood cell transfusions. The golden standard method for determining hemoglobin concentration in blood requires reagent. Spectral methods were advantageous at fast and non-reagent measurement. However, model calibration with full spectrum is time-consuming. Moreover, it is necessary to use a few variables considering size and cost of instrumentation, especially for a portable biomedical instrument. This study presents different wavelength selection methods for optical wavelengths for total hemoglobin concentration determination in whole blood. The results showed that modelling using only two wavelengths combination (1143 nm, 1298 nm) can keep on the fine predictability with full spectrum. It appears that the proper selection of optical wavelengths can be more effective than using the whole spectra for determination hemoglobin in whole blood. We also discussed the influence of water absorptivity on the wavelength selection. This research provides valuable references for designing portable NIR instruments determining hemoglobin concentration, and may provide some experience for noninvasive hemoglobin measurement by NIR methods.

Identification and quantification of major maillard cross-links in human serum albumin and lens protein. Evidence for glucosepane as the dominant compound.

Science.gov (United States)

Biemel, Klaus M; Friedl, D Alexander; Lederer, Markus O

2002-07-12

Glycation reactions leading to protein modifications (advanced glycation end products) contribute to various pathologies associated with the general aging process and long term complications of diabetes. However, only few relevant compounds have so far been detected in vivo. We now report on the first unequivocal identification of the lysine-arginine cross-links glucosepane 5, DOGDIC 6, MODIC 7, and GODIC 8 in human material. For their accurate quantification by coupled liquid chromatography-electrospray ionization mass spectrometry, (13)C-labeled reference compounds were synthesized independently. Compounds 5-8 are formed via the alpha-dicarbonyl compounds N(6)-(2,3-dihydroxy-5,6-dioxohexyl)-l-lysinate (1a,b), 3-deoxyglucosone (), methylglyoxal (), and glyoxal (), respectively. The protein-bound dideoxyosone 1a,b seems to be of prime significance for cross-linking because it presumably is not detoxified by mammalian enzymes as readily as 2-4. Hence, the follow-up product glucosepane 5 was found to be the dominant compound. Up to 42.3 pmol of 5/mg of protein was identified in human serum albumin of diabetics; the level of 5 correlates markedly with the glycated hemoglobin HbA(1c). In the water-insoluble fraction of lens proteins from normoglycemics, concentration of 5 ranges between 132.3 and 241.7 pmol/mg. The advanced glycoxidation end product GODIC 8 is elevated significantly in brunescent lenses, indicating enhanced oxidative stress in this material. Compounds 5-8 thus appear predestined as markers for pathophysiological processes.

PLASMA PROTEIN AND HEMOGLOBIN PRODUCTION

Science.gov (United States)

Robscheit-Robbins, F. S.; Miller, L. L.; Whipple, G. H.

1947-01-01

Given healthy dogs fed abundant iron and protein-free or low protein diets with sustained anemia and hypoproteinemia, we can study the capacity of these animals to produce simultaneously new hemoglobin and plasma protein. Reserve stores of blood protein-building materials are measurably depleted and levels of 6 to 8 gm. per cent for hemoglobin and 4 to 5 gm. per cent for plasma protein can be maintained for weeks or months depending upon the intake of food proteins or amino acid mixtures. These dogs are very susceptible to infection and various poisons. Dogs tire of these diets and loss of appetite terminates many experiments. Under these conditions (double depletion) standard growth mixtures of essential amino acids are tested to show the response in blood protein output and urinary nitrogen balance. As a part of each tabulated experiment one of the essential amino acids is deleted from the complete growth mixture to compare such response with that of the whole mixture. Methionine, threonine, phenylalanine, and tryptophane when singly eliminated from the complete amino acid mixture do effect a sharp rise in urinary nitrogen. This loss of urinary nitrogen is corrected when the individual amino acid is replaced in the mixture. Histidine, lysine, and valine have a moderate influence upon urinary nitrogen balance toward nitrogen conservation. Leucine, isoleucine, and arginine have minimal or no effect upon urinary nitrogen balance when these individual amino acids are deleted from the complete growth mixture of amino acids during 3 to 4 week periods. Tryptophane and to a less extent phenylalanine and threonine when returned to the amino acid mixture are associated with a conspicuous preponderance of plasma protein output over the hemoglobin output (Table 4). Arginine, lysine, and histidine when returned to the amino acid mixture are associated with a large preponderance of hemoglobin output. Various amino acid mixtures under these conditions may give a positive

An analysis of postoperative hemoglobin levels in patients with a fractured neck of femur.

Science.gov (United States)

Nagra, Navraj S; van Popta, Dmitri; Whiteside, Sigrid; Holt, Edward M

2016-10-01

The aim of this study was to analyze the changes in hemoglobin level and to determine a suitable timeline for post-operative hemoglobin monitoring in patients undergoing fixation of femoral neck fracture. Patients who underwent either dynamic hip screw (DHS) fixation (n = 74, mean age: 80 years) or hip hemiarthroplasty (n = 104, mean age: 84 years) for femoral neck fracture were included into the study. The hemoglobin level of the patients was monitored perioperatively. Analysis found a statistically and clinically significant mean drop in hemoglobin of 31.1 g/L over time from pre-operatively (D0) to day-5 post-operatively (p hemoglobin values over hemiarthroplasty patients (p = 0.046). The decrease in hemoglobin in the first 24-h post-operative period (D0 to day-1) is an underestimation of the ultimate lowest value in hemoglobin found at day-2. Relying on the day-1 hemoglobin could be detrimental to patient care. We propose a method of predicting patients likely to be transfused, and recommend a protocol for patients undergoing femoral neck fracture surgery to standardize postoperative hemoglobin monitoring. Level IV Prognostic study. Copyright © 2016 Turkish Association of Orthopaedics and Traumatology. Production and hosting by Elsevier B.V. All rights reserved.

Nitric Oxide in Plants: The Roles of Ascorbate and Hemoglobin

Science.gov (United States)

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. PMID:24376554

Evaluation of non cyanide methods for hemoglobin estimation

Directory of Open Access Journals (Sweden)

Vinaya B Shah

2011-01-01

Full Text Available Background: The hemoglobincyanide method (HiCN method for measuring hemoglobin is used extensively worldwide; its advantages are the ready availability of a stable and internationally accepted reference standard calibrator. However, its use may create a problem, as the waste disposal of large volumes of reagent containing cyanide constitutes a potential toxic hazard. Aims and Objective: As an alternative to drabkin`s method of Hb estimation, we attempted to estimate hemoglobin by other non-cyanide methods: alkaline hematin detergent (AHD-575 using Triton X-100 as lyser and alkaline- borax method using quarternary ammonium detergents as lyser. Materials and Methods: The hemoglobin (Hb results on 200 samples of varying Hb concentrations obtained by these two cyanide free methods were compared with a cyanmethemoglobin method on a colorimeter which is light emitting diode (LED based. Hemoglobin was also estimated in one hundred blood donors and 25 blood samples of infants and compared by these methods. Statistical analysis used was Pearson`s correlation coefficient. Results: The response of the non cyanide method is linear for serially diluted blood samples over the Hb concentration range from 3gm/dl -20 gm/dl. The non cyanide methods has a precision of + 0.25g/dl (coefficient of variation= (2.34% and is suitable for use with fixed wavelength or with colorimeters at wavelength- 530 nm and 580 nm. Correlation of these two methods was excellent (r=0.98. The evaluation has shown it to be as reliable and reproducible as HiCN for measuring hemoglobin at all concentrations. The reagents used in non cyanide methods are non-biohazardous and did not affect the reliability of data determination and also the cost was less than HiCN method. Conclusions: Thus, non cyanide methods of Hb estimation offer possibility of safe and quality Hb estimation and should prove useful for routine laboratory use. Non cyanide methods is easily incorporated in hemobloginometers

Megalin and cubilin are endocytic receptors involved in renal clearance of hemoglobin

DEFF Research Database (Denmark)

Gburek, Jakub; Verroust, Pierre J; Willnow, Thomas E

2002-01-01

-Sepharose affinity chromatography of solubilized renal brush-border membranes. Apparent dissociation constants of 1.7 microM for megalin and 4.1 microM for cubilin were determined by surface plasmon resonance analysis. The binding was calcium dependent in both cases. Uptake of fluorescence-labeled hemoglobin by BN......The kidney is the main site of hemoglobin clearance and degradation in conditions of severe hemolysis. Herein it is reported that megalin and cubilin, two epithelial endocytic receptors, mediate the uptake of hemoglobin in renal proximal tubules. Both receptors were purified by use of hemoglobin...... not affect the uptake. By use of immunohistochemistry, it was demonstrated that uptake of hemoglobin in proximal tubules of rat, mouse, and dog kidneys occurs under physiologic conditions. Studies on normal and megalin knockout mouse kidney sections showed that megalin is responsible for physiologic...

Role of Reversible Histidine Coordination in Hydroxylamine Reduction by Plant Hemoglobins (Phytoglobins).

Science.gov (United States)

Athwal, Navjot Singh; Alagurajan, Jagannathan; Andreotti, Amy H; Hargrove, Mark S

2016-10-18

Reduction of hydroxylamine to ammonium by phytoglobin, a plant hexacoordinate hemoglobin, is much faster than that of other hexacoordinate hemoglobins or pentacoordinate hemoglobins such as myoglobin, leghemoglobin, and red blood cell hemoglobin. The reason for differences in reactivity is not known but could be intermolecular electron transfer between protein molecules in support of the required two-electron reduction, hydroxylamine binding, or active site architecture favoring the reaction. Experiments were conducted with phytoglobins from rice, tomato, and soybean along with human neuroglobin and soybean leghemoglobin that reveal hydroxylamine binding as the rate-limiting step. For hexacoordinate hemoglobins, binding is limited by the dissociation rate constant for the distal histidine, while leghemoglobin is limited by an intrinsically low affinity for hydroxylamine. When the distal histidine is removed from rice phytoglobin, a hydroxylamine-bound intermediate is formed and the reaction rate is diminished, indicating that the distal histidine imidazole side chain is critical for the reaction, albeit not for electron transfer but rather for direct interaction with the substrate. Together, these results demonstrate that phytoglobins are superior at hydroxylamine reduction because they have distal histidine coordination affinity constants near 1, and facile rate constants for binding and dissociation of the histidine side chain. Hexacoordinate hemoglobins such as neuroglobin are limited by tighter histidine coordination that blocks hydroxylamine binding, and pentacoordinate hemoglobins have intrinsically lower hydroxylamine affinities.

Placental morphology at different maternal hemoglobin levels: a histopathological study

International Nuclear Information System (INIS)

Kiran, N.; Zubair, A.; Malik, T.M.

2015-01-01

To evaluate the histopathological parameters of the placenta like weight, infarct and syncytial knots, at different maternal hemoglobin levels, in both qualitative and quantitative manner. Study design: Descriptive study Place and Duration of Study: Army Medical College, National University of Sciences and Technology in collaboration with Department of Obstetrics and Gynecology, Military Hospital, Rawalpindi, Pakistan, from December 2011 to November 2012. Patients and Methods: A total of 75 placentas were included, that were collected from full term mothers at the time of childbirth. Placental weight was taken without umbilical cord and gross placental infarcts were noted. Samples of placental tissue were taken and stained by haematoxylin and eosin (H and E). Microscopic study was done to evaluate placental infarcts and syncytial knots. Results: Mean placental weight at normal and low maternal hemoglobin was 581.67 ± 83.97g and 482.58 ± 104.74g respectively. Gross placental infarcts were found in all cases having low maternal hemoglobin concentration (60% cases). Syncytial knots were found in all placentas but they were considerably more at decreasing levels of maternal hemoglobin (19.79 ± 5.22). Conclusion: The present study showed decrease in placental weight, increase in placental infarcts and syncytial knot hyperplasia at low maternal hemoglobin concentration, displaying adaptive alterations. (author)

The refractive index of human hemoglobin in the visible range

International Nuclear Information System (INIS)

Zhernovaya, O; Tuchin, V; Sydoruk, O; Douplik, A

2011-01-01

Because the refractive index of hemoglobin in the visible range is sensitive to the hemoglobin concentration, optical investigations of hemoglobin are important for medical diagnostics and treatment. Direct measurements of the refractive index are, however, challenging; few such measurements have previously been reported, especially in a wide wavelength range. We directly measured the refractive index of human deoxygenated and oxygenated hemoglobin for nine wavelengths between 400 and 700 nm for the hemoglobin concentrations up to 140 g l -1 . This paper analyzes the results and suggests a set of model functions to calculate the refractive index depending on the concentration. At all wavelengths, the measured values of the refractive index depended on the concentration linearly. Analyzing the slope of the lines, we determined the specific refraction increments, derived a set of model functions for the refractive index depending on the concentration, and compared our results with those available in the literature. Based on the model functions, we further calculated the refractive index at the physiological concentration within the erythrocytes of 320 g l -1 . The results can be used to calculate the refractive index in the visible range for arbitrary concentrations provided that the refractive indices depend on the concentration linearly.

Current hemoglobin levels are more predictive of disease progression than hemoglobin measured at baseline in patients receiving antiretroviral treatment for HIV type 1 infection

DEFF Research Database (Denmark)

Kowalska, Justyna D; Mocroft, Amanda; Blaxhult, Anders

2007-01-01

The role of hemoglobin levels as an independent prognostic marker of progression to AIDS and/or death in HIV-infected patients starting combination antiretroviral therapy (cART) was investigated. A total of 2,579 patients from the EuroSIDA cohort with hemoglobin, CD4 cell count, and HIV RNA viral...

A new polyethyleneglycol-derivatized hemoglobin derivative with decreased oxygen affinity and limited toxicity.

Science.gov (United States)

Zolog, Oana; Mot, Augustin; Deac, Florina; Roman, Alina; Fischer-Fodor, Eva; Silaghi-Dumitrescu, Radu

2011-01-01

A new protocol is described for derivatization of hemoglobin with polyethyleneglycol (PEG) via reaction of the unmodified native hemoglobin with an activated amine-reacting polyethylene glycol derivative which, unlike protocols previously described, leads to formation of a peptide bond between hemoglobin and PEG. Dioxygen binding and peroxide reactivities of the derivatized hemoglobin are examined, and found to be within reasonable limits, with the particular observation that, unlike with a few other derivatization protocols, the dioxygen affinity is slightly lower than that of native Hb. In cell culture tests (human umbilical vein epithelial cells, HUVEC), the derivatization protocol induces no toxic effect. These results show promise towards applicability for production of hemoglobin-based blood substitutes.

Consequential secondary structure alterations and aggregation during prolonged casein glycation.

Science.gov (United States)

Jindal, Supriya; Naeem, Aabgeena

2013-05-01

Non-enzymatic glycosylation (glycation) of casein is a process used not just to ameliorate the quality of dairy products but also to increase the shelf life of canned foods, including baby milk supplements. Incubation of κ-casein with reducing sugars for 15 days at physiological temperature showed the formation of a molten globule state at day 9 and 12 during fructation and glucation respectively. This state exhibits substantial secondary structure and maximum ANS binding. Later on, glycation resulted in the formation of aggregates at day 12 in presence of fructose and day 15 in presence of glucose. Aggregates possess extensive β-sheet structure as revealed by far-UV CD and FTIR. These aggregates showed altered tryptophan environment, decrease ANS binding relative to molten globule state and increase in Thioflavin T fluorescence. Aggregates were also accompanied by the accumulation of AGEs, indicative of structural damage to the protein and formation of potentially harmful species at the physiological level. Fructose was more reactive than glucose and thus caused early and significant changes in the protein. From our studies, we conclude that controlling the extent of the Maillard reaction in the food industry is essential to counter its negative effects and expand its safety spectrum.

Haptoglobin radioassay based on binding to solid-phase hemoglobin

International Nuclear Information System (INIS)

Hooper, D.C.; Reed, R.A.; Peacock, A.C.

1979-01-01

A specific and sensitive assay for haptoglobin based on binding to an easily prepred Sepharose-bound hemoglobin reagent is described. The assay is suitable for directly determining radiolabeled amino acid incorporation into haptoglobin in several liver cell systems in vitro and can be adapted to measure unlabeled free haptoglobin in plasma samples regardlss of the presence of the haptoglobin--hemoglobin complex

Bio-optic signatures for advanced glycation end products in the skin in streptozotocin (STZ) Induced Diabetes (Conference Presentation)

Science.gov (United States)

Saidian, Mayer; Ponticorvo, Adrien; Rowland, Rebecca A.; Balbado, Melisa L.; Lentsch, Griffin; Balu, Mihaela; Alexander, Micheal; Shiri, Li; Lakey, Jonathan R. T.; Durkin, Anthony J.; Kohen, Roni; Tromberg, Bruce J.

2017-02-01

Type 1diabetes (T1D) is an autoimmune disorder that occurs due to the rapid destruction of insulin-producing beta cells, leading to insulin deficiency and the inability to regulate blood glucose levels and leads to destructive secondary complications. Advanced glycation end (AGEs) products, the result of the cross-linking of reducing sugars and proteins within the tissues, are one of the key causes of major complications associated with diabetes such as renal failure, blindness, nerve damage and vascular changes. Non-invasive techniques to detect AGEs are important for preventing the harmful effects of AGEs during diabetes mellitus. In this study, we utilized multiphoton microscopy to image biopsies taken from control rats and compared them to biopsies taken from streptozotocin (STZ) induced adult male diabetic rats. This was done at two and four weeks after the induction of hyperglycemia (>400 mg/dL) specifically to evaluate the effects of glycation on collagen. We chose to use an in-situ multiphoton microscopy method that combines multiphoton auto-florescence (AF) and second harmonic generation (SHG) to detect the microscopic influence of glycation. Initial results show high auto-florescence levels were present on the collagen, as a result of the accumulation of AGEs only two weeks after the STZ injection and considerably higher levels were present four weeks after the STZ injection. Future projects could involve evaluating advanced glycation end products in a clinical trial of diabetic patients.

Nephrin expression is reduced in human diabetic nephropathy: evidence for a distinct role for glycated albumin and angiotensin II.

Science.gov (United States)

Doublier, Sophie; Salvidio, Gennaro; Lupia, Enrico; Ruotsalainen, Vesa; Verzola, Daniela; Deferrari, Giacomo; Camussi, Giovanni

2003-04-01

We studied the distribution of nephrin in renal biopsies from 17 patients with diabetes and nephrotic syndrome (7 type 1 and 10 type 2 diabetes), 6 patients with diabetes and microalbuminuria (1 type 1 and 5 type 2 diabetes), and 10 normal subjects. Nephrin expression was semiquantitatively evaluated by measuring immunofluorescence intensity by digital image analysis. We found an extensive reduction of nephrin staining in both type 1 (67 +/- 9%; P < 0.001) and type 2 (65 +/- 10%; P < 0.001) diabetic patients with diabetes and nephrotic syndrome when compared with control subjects. The pattern of staining shifted from punctate/linear distribution to granular. In patients with microalbuminuria, the staining pattern of nephrin also showed granular distribution and reduction intensity of 69% in the patient with type 1 diabetes and of 62 +/- 4% (P < 0.001) in the patients with type 2 diabetes. In vitro studies on human cultured podocytes demonstrated that glycated albumin and angiotensin II reduced nephrin expression. Glycated albumin inhibited nephrin synthesis through the engagement of receptor for advanced glycation end products, whereas angiotensin II acted on cytoskeleton redistribution, inducing the shedding of nephrin. This study indicates that the alteration in nephrin expression is an early event in proteinuric patients with diabetes and suggests that glycated albumin and angiotensin II contribute to nephrin downregulation.

Microalbuminuria and glycated hemoglobin in children with type 1 ...

African Journals Online (AJOL)

Magdy A. Omar

2014-06-02

Jun 2, 2014 ... and diastolic blood pressure among diabetic children with and without MA (P = 0.556 and 0.781). ... decreased rates of microvascular complications (retinopathy, .... developments that allow the detection of minor abnormalities.

Advanced Glycation End-Products affect transcription factors regulating insulin gene expression

International Nuclear Information System (INIS)

Puddu, A.; Storace, D.; Odetti, P.; Viviani, G.L.

2010-01-01

Advanced Glycation End-Products (AGEs) are generated by the covalent interaction of reducing sugars with proteins, lipids or nucleic acids. AGEs are implicated in diabetic complications and pancreatic β-cell dysfunction. We previously demonstrated that exposure of the pancreatic islet cell line HIT-T15 to high concentrations of AGEs leads to a significant decrease of insulin secretion and content. Insulin gene transcription is positively regulated by the beta cell specific transcription factor PDX-1 (Pancreatic and Duodenal Homeobox-1). On the contrary, the forkhead transcription factor FoxO1 inhibits PDX-1 gene transcription. Activity of FoxO1 is regulated by post-translational modifications: phosphorylation deactivates FoxO1, and acetylation prevents FoxO1 ubiquitination. In this work we investigated whether AGEs affect expression and subcellular localization of PDX-1 and FoxO1. HIT-T15 cells were cultured for 5 days in presence of AGEs. Cells were then lysed and processed for subcellular fractionation. We determined intracellular insulin content, then we assessed the expression and subcellular localization of PDX-1, FoxO1, phosphoFoxO1 and acetylFoxO1. As expected intracellular insulin content was lower in HIT-T15 cells cultured with AGEs. The results showed that AGEs decreased expression and nuclear localization of PDX-1, reduced phosphorylation of FoxO1, and increased expression and acetylation of FoxO1. These results suggest that AGEs decrease insulin content unbalancing transcription factors regulating insulin gene expression.

Genetic and developmental variation of hemoglobin in the deermouse, Peromyscus maniculatus.

Science.gov (United States)

Maybank, K M; Dawson, W D

1976-04-01

A genetic investigation of electrophoretic hemoglobin variants of the deermouse, Peromyscus maniculatus, shows three alleles, Hblf, Hblr, and Hblo, at a duplicated site controlling the six adult phenotypes. The Hblf allele has not been described previously. The hemoglobin locus is not closely linked to the albino locus. Fetal hemoglobin is distinct from any of the adult components and has a slower electrophoretic mobility. The fetal phenotype changes to the adult type between the days 15 and 18 of prenatal life.

Relationship between advanced glycation end-products with the severity of chronic heart failure in 85 patients

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Amir Farhang Zand Parsa

2013-12-01

Full Text Available Background: Advanced glycation end-products (AGEs came up with the recent researches regarding new biomarkers for the diagnosis of heart failure. AGEs are the end products of non-enzymatic glycation and oxidation of proteins, lipids and nucleotides during Maillard biochemical reaction. Although it has been known that AGEs have a role in the pathogenesis of chronic heart failure (CHF, information regarding its role and its pathogenetic mechanism is very limited. The aim of this study was to find any relationship between AGEs with the etiology and severity of chronic heart failure.Methods: This study is a prospective cross sectional study that enrolled 85 patients with chronic heart failure. Measurement of left ventricle ejection fraction (LVEF was done by echocardiography. Blood samples were collected for measuring AGEs just before or after echocardiography assessment (in the same session. Measurement of AGEs was done by the enzyme-linked immunosorbent assay (ELISA method. The relationship between AGEs with the severity of CHF and as well as the etiology of CHF were evaluated via SPSS-15.Results: Of 85 patients 48 (56.5% patients were male and 37 (43.5% were female; Mean±SD of their ages was 55.8±13.4 years old (ranges from 27 to 84 years. Correlation coefficient between LVEF and AGEs was 0.269 (P=0.013. Mean of AGEs in patients with and without ischemic etiology of their heart failure were 16.8±9.8µg/ml and 11.6±7.3 µg/ml, respectively. Although trend was in favor of ischemic heart failure, the difference between two groups was not statistically significant (P= 0.141.Conclusion: According to this study the rate of AGES could be helpful in the diagnosis and assessment of severity of CHF. Based on our findings, higher blood levels of AGEs in the ischemic CHF cases, also it could be concluded that in the future this marker may be used for etiologic differentiation of heart failure syndrome.

Hemoglobin is essential for normal growth of Arabidopsis organs

DEFF Research Database (Denmark)

Hebelstrup, Kim Henrik; Hunt, Peter; Dennis, Elizabeth

2006-01-01

In Arabidopsis thaliana, the class I hemoglobin AHb1 is transiently expressed in the hydathodes of leaves and in floral buds from young inflorescences. Nitric oxide (NO) accumulates to high levels in these organs when AHb1 is silenced, indicating an important role in metabolizing NO. AHb1-silence...... suggests that 3-on-3 hemoglobins apart from a role in hypoxic stress play a general role under non-stressed conditions where they are essential for normal development by controlling the level of NO which tends to accumulate in floral buds and leaf hydathodes of plants......In Arabidopsis thaliana, the class I hemoglobin AHb1 is transiently expressed in the hydathodes of leaves and in floral buds from young inflorescences. Nitric oxide (NO) accumulates to high levels in these organs when AHb1 is silenced, indicating an important role in metabolizing NO. AHb1-silenced...... lines are viable but show a mutant phenotype affecting the regions where AHb1 is expressed. Arabidopsis lines with an insertional knockout or overexpression of AHb2, a class II 3-on-3 hemoglobin, were generated. Seedlings overexpressing AHb2 show enhanced survival of hypoxic stress. The AHb2 knockout...

Simultaneous pre-concentration and separation on simple paper-based analytical device for protein analysis.

Science.gov (United States)

Niu, Ji-Cheng; Zhou, Ting; Niu, Li-Li; Xie, Zhen-Sheng; Fang, Fang; Yang, Fu-Quan; Wu, Zhi-Yong

2018-02-01

In this work, fast isoelectric focusing (IEF) was successfully implemented on an open paper fluidic channel for simultaneous concentration and separation of proteins from complex matrix. With this simple device, IEF can be finished in 10 min with a resolution of 0.03 pH units and concentration factor of 10, as estimated by color model proteins by smartphone-based colorimetric detection. Fast detection of albumin from human serum and glycated hemoglobin (HBA1c) from blood cell was demonstrated. In addition, off-line identification of the model proteins from the IEF fractions with matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS) was also shown. This PAD IEF is potentially useful either for point of care test (POCT) or biomarker analysis as a cost-effective sample pretreatment method.

Clinical Value of High Mobility Group Box 1 and the Receptor for Advanced Glycation End-products in Head and Neck Cancer: A Systematic Review

Directory of Open Access Journals (Sweden)

Nguyen, Austin

2016-04-01

Full Text Available Introduction High mobility group box 1 is a versatile protein involved in gene transcription, extracellular signaling, and response to inflammation. Extracellularly, high mobility group box 1 binds to several receptors, notably the receptor for advanced glycation end-products. Expression of high mobility group box 1 and the receptor for advanced glycation end-products has been described in many cancers. Objectives To systematically review the available literature using PubMed and Web of Science to evaluate the clinical value of high mobility group box 1 and the receptor for advanced glycation end-products in head and neck squamous cell carcinomas. Data synthesis A total of eleven studies were included in this review. High mobility group box 1 overexpression is associated with poor prognosis and many clinical and pathological characteristics of head and neck squamous cell carcinomas patients. Additionally, the receptor for advanced glycation end-products demonstrates potential value as a clinical indicator of tumor angiogenesis and advanced staging. In diagnosis, high mobility group box 1 demonstrates low sensitivity. Conclusion High mobility group box 1 and the receptor for advanced glycation end-products are associated with clinical and pathological characteristics of head and neck squamous cell carcinomas. Further investigation of the prognostic and diagnostic value of these molecules is warranted.

Glycation-assisted synthesized gold nanoparticles inhibit growth of bone cancer cells.

Science.gov (United States)

Rahim, Moniba; Iram, Sana; Khan, Mohd Sajid; Khan, M Salman; Shukla, Ankur R; Srivastava, A K; Ahmad, Saheem

2014-05-01

This study presents a novel approach to synthesize glycogenic gold nanoparticles (glycogenic GNps) capped with glycated products (Schiff's base, Heyns products, fructosylamine etc.). These glycogenic GNps have been found to be active against human osteosarcoma cell line (Saos-2) with an IC50 of 0.187 mM, while the normal human embryonic lung cell line (L-132) remained unaffected up to 1mM concentration. The size of glycogenic GNps can also be controlled by varying the time of incubation of gold solution. Glycation reactions involving a combination of fructose and HSA (Human Serum Albumin) were found to be effective in the reduction of gold to glycogenic GNps whereas glucose in combination with HSA did not result in the reduction of gold. The progress of the reaction was followed using UV-visible spectroscopy and NBT (Nitroblue tetrazolium) assay. The glycogenic GNps were found to be spherical in shape with an average size of 24.3 nm, in a stable emulsion. These GNps were characterized using UV-visible spectroscopy, zeta potential analysis, transmission electron microscopy (TEM) and scanning electron microscopy (SEM). Copyright © 2013 Elsevier B.V. All rights reserved.

Determination of supplier-to-supplier and lot-to-lot variability in glycation of recombinant human serum albumin expressed in Oryza sativa.

Directory of Open Access Journals (Sweden)

Grant E Frahm

Full Text Available The use of different expression systems to produce the same recombinant human protein can result in expression-dependent chemical modifications (CMs leading to variability of structure, stability and immunogenicity. Of particular interest are recombinant human proteins expressed in plant-based systems, which have shown particularly high CM variability. In studies presented here, recombinant human serum albumins (rHSA produced in Oryza sativa (Asian rice (OsrHSA from a number of suppliers have been extensively characterized and compared to plasma-derived HSA (pHSA and rHSA expressed in yeast (Pichia pastoris and Saccharomyces cerevisiae. The heterogeneity of each sample was evaluated using size exclusion chromatography (SEC, reversed-phase high-performance liquid chromatography (RP-HPLC and capillary electrophoresis (CE. Modifications of the samples were identified by liquid chromatography-mass spectrometry (LC-MS. The secondary and tertiary structure of the albumin samples were assessed with far U/V circular dichroism spectropolarimetry (far U/V CD and fluorescence spectroscopy, respectively. Far U/V CD and fluorescence analyses were also used to assess thermal stability and drug binding. High molecular weight aggregates in OsrHSA samples were detected with SEC and supplier-to-supplier variability and, more critically, lot-to-lot variability in one manufactures supplied products were identified. LC-MS analysis identified a greater number of hexose-glycated arginine and lysine residues on OsrHSA compared to pHSA or rHSA expressed in yeast. This analysis also showed supplier-to-supplier and lot-to-lot variability in the degree of glycation at specific lysine and arginine residues for OsrHSA. Both the number of glycated residues and the degree of glycation correlated positively with the quantity of non-monomeric species and the chromatographic profiles of the samples. Tertiary structural changes were observed for most OsrHSA samples which

Aspartic protease activities of schistosomes cleave mammalian hemoglobins in a host-specific manner

Directory of Open Access Journals (Sweden)

Jeffrey W Koehler

2007-02-01

Full Text Available We examined the efficiency of digestion of hemoglobin from four mammalian species, human, cow, sheep, and horse by acidic extracts of mixed sex adults of Schistosoma japonicum and S. mansoni. Activity ascribable to aspartic protease(s from S. japonicum and S. mansoni cleaved human hemoglobin. In addition, aspartic protease activities from S. japonicum cleaved hemoglobin from bovine, sheep, and horse blood more efficiently than did the activity from extracts of S. mansoni. These findings support the hypothesis that substrate specificity of hemoglobin-degrading proteases employed by blood feeding helminth parasites influences parasite host species range; differences in amino acid sequences in key sites of the parasite proteases interact less or more efficiently with the hemoglobins of permissive or non-permissive hosts.

A microfluidic approach for hemoglobin detection in whole blood

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Nikita Taparia

2017-10-01

Full Text Available Diagnosis of anemia relies on the detection of hemoglobin levels in a blood sample. Conventional blood analyzers are not readily available in most low-resource regions where anemia is prevalent, so detection methods that are low-cost and point-of-care are needed. Here, we present a microfluidic approach to measure hemoglobin concentration in a sample of whole blood. Unlike conventional approaches, our microfluidic approach does not require hemolysis. We detect the level of hemoglobin in a blood sample optically by illuminating the blood in a microfluidic channel at a peak wavelength of 540 nm and measuring its absorbance using a CMOS sensor coupled with a lens to magnify the image onto the detector. We compare measurements in microchannels with channel heights of 50 and 115 μm and found the channel with the 50 μm height provided a better range of detection. Since we use whole blood and not lysed blood, we fit our data to an absorption model that includes optical scattering in order to obtain a calibration curve for our system. Based on this calibration curve and data collected, we can measure hemoglobin concentration within 1 g/dL for severe cases of anemia. In addition, we measured optical density for blood flowing at a shear rate of 500 s-1 and observed it did not affect the nonlinear model. With this method, we provide an approach that uses microfluidic detection of hemoglobin levels that can be integrated with other microfluidic approaches for blood analysis.

A microfluidic approach for hemoglobin detection in whole blood

Science.gov (United States)

Taparia, Nikita; Platten, Kimsey C.; Anderson, Kristin B.; Sniadecki, Nathan J.

2017-10-01

Diagnosis of anemia relies on the detection of hemoglobin levels in a blood sample. Conventional blood analyzers are not readily available in most low-resource regions where anemia is prevalent, so detection methods that are low-cost and point-of-care are needed. Here, we present a microfluidic approach to measure hemoglobin concentration in a sample of whole blood. Unlike conventional approaches, our microfluidic approach does not require hemolysis. We detect the level of hemoglobin in a blood sample optically by illuminating the blood in a microfluidic channel at a peak wavelength of 540 nm and measuring its absorbance using a CMOS sensor coupled with a lens to magnify the image onto the detector. We compare measurements in microchannels with channel heights of 50 and 115 μm and found the channel with the 50 μm height provided a better range of detection. Since we use whole blood and not lysed blood, we fit our data to an absorption model that includes optical scattering in order to obtain a calibration curve for our system. Based on this calibration curve and data collected, we can measure hemoglobin concentration within 1 g/dL for severe cases of anemia. In addition, we measured optical density for blood flowing at a shear rate of 500 s-1 and observed it did not affect the nonlinear model. With this method, we provide an approach that uses microfluidic detection of hemoglobin levels that can be integrated with other microfluidic approaches for blood analysis.

Concurrent measurement of cellular turbidity and hemoglobin to evaluate the antioxidant activity of plants.

Science.gov (United States)

Bellik, Yuva; Iguer-Ouada, Mokrane

2016-01-01

In past decades, a multitude of analytical methods for measuring antioxidant activity of plant extracts has been developed. However, when using methods to determine hemoglobin released from human erythrocytes treated with ginger extracts, we found hemoglobin concentrations were significantly higher than in untreated control samples. This suggests in the presence of antioxidants that measuring hemoglobin alone is not sufficient to determine hemolysis. We show concurrent measurement of erythrocyte concentration and hemoglobin is essential in such assays, and describe a new protocol based on simultaneous measurement of cellular turbidity and hemoglobin. Copyright © 2015 Elsevier Ltd. All rights reserved.

Characterizing harmful advanced glycation end-products (AGEs) and ribosylated aggregates of yellow mustard seed phytocystatin: Effects of different monosaccharides

Science.gov (United States)

Ahmed, Azaj; Shamsi, Anas; Bano, Bilqees

2017-01-01

Advanced glycation end products (AGEs) are at the core of variety of diseases ranging from diabetes to renal failure and hence gaining wide consideration. This study was aimed at characterizing the AGEs of phytocystatin isolated from mustard seeds (YMP) when incubated with different monosaccharides (glucose, ribose and mannose) using fluorescence, ultraviolet, circular dichroism (CD) spectroscopy and microscopy. Ribose was found to be the most potent glycating agent as evident by AGEs specific fluorescence and absorbance. YMP exists as a molten globule like structure on day 24 as depicted by high ANS fluorescence and altered intrinsic fluorescence. Glycated YMP as AGEs and ribose induced aggregates were observed at day 28 and 32 respectively. In our study we have also examined the anti-aggregative potential of polyphenol, resveratrol. Our results suggested the anti-aggregative behavior of resveratrol as it prevented the in vitro aggregation of YMP, although further studies are required to decode the mechanism by which resveratrol prevents the aggregation.

Total soluble and endogenous secretory receptor for advanced glycation endproducts (RAGE) in IBD

NARCIS (Netherlands)

Meijer, Berrie; Hoskin, Teagan; Ashcroft, Anna; Burgess, Laura; Keenan, Jacqueline I.; Falvey, James; Gearry, Richard B.; Day, Andrew S.

2014-01-01

Recruitment and activation of neutrophils, with release of specific proteins such as S100 proteins, is a feature of inflammatory bowel disease (IBD). Soluble forms of the receptor for advanced glycation endproducts (sRAGE), and variants such as endogenous secretory (esRAGE), can act as decoy

Study of methyl bromide reactivity with human and mouse hemoglobin

African Journals Online (AJOL)

A study has been carried out on in-vitro reactivity of human and mouse hemoglobin spectrophotometrically at physiological pH, using different protein to reagent ratios. Hemoglobin side chains were modified with different concentrations of methyl bromide on agro-soil fumigant. To ascertain if the site of alkylation was the ...

Induction of nano pore in Agrobacterial hemoglobin

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Mojtaba Tousheh

2014-01-01

Full Text Available Introduction: A variety of oxygen-transport and -binding proteins exist in organisms including bacteria, protozoans, and fungi all have hemoglobin-like proteins. In addition to dealing with transport and sensing of oxygen, they may also deal with NO2, CO2, sulfide compounds, and even O2 scavenging in environments. Also they detoxified chlorinated materials like P450 enzymes and peroxidases and use as a detector of nitrate and hydrogen peroxide. Pore-forming bacterial globins are interested for filtration. Materials and methods: Although there are data for bacterial toxin as a filter, here we used Agrobacterial hem to induce nano pore in the heme structure using point mutation. Results: Investigations showed that three amino acids leucine 76, alanine 83 and histidine 80 are important for pore formation in Agrobacterium hemoglobin. A point mutation on leucine 76 to glycine, histidine 80 to asparagine and alanine 83 to lysine step by step led to create the nano pore 0.7- 0.8 nm in the globin. Discussion and conclusion: These mutations in bacterial hemoglobin increase the stability when mutation is with it’s at pH7. This mutation decreases the aliphatic index however increase the stability index.

Purification, characterization and sequence analyses of the extracellular giant hemoglobin from Oligobrachia mashikoi

OpenAIRE

Nakagawa, Taro; Onoda, Seiko; Kanemori, Masaaki; Sasayama, Yuichi; Fukumori, Yoshihiro

2005-01-01

We purified an extracellular hemoglobin with the molecular mass of ca. 440 kDa from the whole homogenates of Oligobrachia mashikoi (phylum Pogonophora) by a one-step gel-filtration. The preparation was pure to be crystallized. The P50 values of the hemoglobin and the fresh blood prepared from O. mashikoi were about 0.82 Torr and 0.9 Torr, respectively, which were much lower than the P50 value of human hemoglobin. However, the n values of the hemoglobin and the blood were about 1.2 and 1.1, re...

Blood hemoglobin level and treatment outcome of early breast cancer

International Nuclear Information System (INIS)

Henke, M.; Sindlinger, F.; Ikenberg, H.; Gerds, T.; Schumacher, M.

2004-01-01

Background and purpose: to determine whether the blood hemoglobin concentration correlates with the prognosis of patients with early breast cancer and, if so, whether this is restricted to treatment modality. Patients and methods: data were collected retrospectively from patients with early breast cancer (T1,2 NO-2 MO) who underwent either breast-conserving surgery followed by adjuvant radiotherapy (BCS-RT; n = 96) or a modified radical mastectomy (MRM; n = 194). The effect of preoperative blood hemoglobin level, nodal status, histological grading and hormone receptor status on disease-free survival was determined for both treatment modalities using a cox regression model and visualized by kaplan-meier plots. Results: the blood hemoglobin concentration significantly correlated with disease-free survival of patients receiving BCS-RT (relative risk [RR]: 0.67 per g/dl; p = 0.007). This was independent of other known risk factors for breast cancer patients, as determined by multivariate analysis. By contrast, the blood hemoglobin level had no prognostic significance when patients were treated with MRM. Conclusion: blood hemoglobin concentration seems to affect the prognosis of patients with early breast cancer when a treatment schedule that includes radiotherapy is applied. Reduced radiosensitivity due to diminished tumor oxygenation may be the underlying cause. Confirmative trials and studies intended to elucidate the underlying mechanism are warranted. (orig.)

NITRITE REDUCTASE ACTIVITY OF NON-SYMBIOTIC HEMOGLOBINS FROM ARABIDOPSIS THALIANA†