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.

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

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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.

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

Science.gov (United States)

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

Dyslipidemia is quite prevalent in non-insulin dependent diabetes mellitus. Maintaining tight glycemic along with lipid control plays an essential role in preventing micro- and macro-vascular complications associated with diabetes. The main purpose of the study was to highlight the relationship between glycosylated hemoglobin (HbA1c) and triglyceride levels. This may in turn help in predicting the triglyceride status of type 2 diabetics and therefore identifying patients at increased risk from cardiovascular events. Hypertriglyceridemia is one of the common risk factors for coronary artery disease in type 2 diabetes mellitus (DM). Careful monitoring of the blood glucose level can be used to predict lipid status and can prevent most of the complications associated with the disease. This is a cross-sectional study using data collected from the outpatient diabetic clinic of Jinnah Postgraduate Medical Centre (JPMC) Karachi, Pakistan. Patients of age 18 years and above were recruited from the clinic. A total of consenting 509 patients of type 2 diabetes mellitus were enrolled over a period of 11 months.  For statistical analysis, SPSS Statistics for Windows, Version 17.0 ( IBM Corp, Armonk, New York) was used and Chi-square and Pearson's correlation coefficient was used to find the association between triglyceride and HbA1c. The HbA1c was dichotomized into four groups on the basis of cut-off. Chi-square was used for association between HbA1c with various cut-off values and high triglyceride levels. Odds-ratio and its 95% confidence interval were calculated to estimate the level of risk between high triglyceride levels and HbA1c groups. The p-value triglyceride was evaluated in four different groups of HbA1c, with a cut-off seven, eight, nine and 10 respectively. With HbA1c cut-off value of 7%, 74% patients had high triglycerides and showed a significant association with high triglyceride levels at p index, lifestyle) and health status factors (blood pressure

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)

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.

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...

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

Science.gov (United States)

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.

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...

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.

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)

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.

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

Science.gov (United States)

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.

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

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

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.

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.

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

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

2015-01-01

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

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.

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 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.

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-(...

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

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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.

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.

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.

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.

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

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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.

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.

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.

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.

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.

Evidence for Consistency of the Glycation Gap in Diabetes

OpenAIRE

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...

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

Science.gov (United States)

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

[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.

Hemoglobin cut-off values in healthy Turkish infants

Institute of Scientific and Technical Information of China (English)

Ahmet Arvas; Emel Gür; DurmuşDoğan

2014-01-01

Background: Anemia is a widespread public health problem associated with an increased risk of morbidity and mortality. This study was undertaken to determine the cut-off value of hemoglobin for infant anemia. Methods: A cross-sectional retrospective study was carried out at well-baby clinics of a tertiary care hospital. A total of 1484 healthy infants aged between 4 to 24 months were included in the study. The relationship of hemoglobin (Hb) levels with mother age, birth weight, weight gain rate, feeding, and gender was evaluated. Results: The Hb levels were assessed in four age groups (4 months, 6 months, 9-12 months, and 15-24 months) and the cut-off values of Hb were determined. Hb cut-off values (5th percentile for age) were detected as 97 g/L and 93 g/L at 4 months and 6 months, respectively. In older infants, the 5th percentile was 90.5 g/L and 93.4 g/L at 9-12 months and 15-24 months, respectively. The two values were lower than the World Health Organization criteria for anemia, which could partly due to the lack of information on iron status in our population. However, this difference highlights the need for further studies on normal Hb levels in healthy infants in developing countries. Hb levels of females were higher in all age groups; however, a statistically significant difference was found in gender in only 6 month-old infants. No statistically significant difference was found among Hb levels, mother's age, birth weight, weight gain rate, and nutritional status. Conclusion: Hb cut-off values in infants should be re-evaluated and be compatible with growth and development of children in that community.

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, 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.

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.

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)

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 ...

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.

Hemoglobin (image)

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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 ...

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

Science.gov (United States)

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.

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

Directory of Open Access Journals (Sweden)

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.

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.

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...

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

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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

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.

Possible discrepancy of HbA1c values and its assessment among patients with chronic renal failure, hemodialysis and other diseases.

Science.gov (United States)

Inoue, Kaori; Goto, Atsushi; Kishimoto, Miyako; Tsujimoto, Tetsuro; Yamamoto-Honda, Ritsuko; Noto, Hiroshi; Kajio, Hiroshi; Terauchi, Yasuo; Noda, Mitsuhiko

2015-12-01

Glycated hemoglobin (HbA1c) and glycated albumin (GA) are frequently used as glycemic control markers. However, these markers are influenced by alterations in hemoglobin and albumin metabolism. Thus, conditions such as anemia, chronic renal failure, hypersplenism, chronic liver diseases, hyperthyroidism, hypoalbuminemia, and pregnancy need to be considered when interpreting HbA1c or GA values. Using data from patients with normal albumin and hemoglobin metabolism, we previously established a linear regression equation describing the GA value versus the HbA1c value to calculate an extrapolated HbA1c (eHbA1c) value for the accurate evaluation of glycemic control. In this study, we investigated the difference between the measured HbA1c and the eHbA1c values for patients with various conditions. Data sets for a total of 2461 occasions were obtained from 731 patients whose HbA1c and GA values were simultaneously measured. We excluded patients with missing data or changeable HbA1c levels, and patients who had received transfusions or steroids within the previous 3 months. Finally, we included 44 patients with chronic renal failure (CRF), 10 patients who were undergoing hemodialysis (HD), 7 patients with hematological malignancies and a hemoglobin level of less than 10 g/dL (HM), and 12 patients with chronic liver diseases (CLD). In all the groups, the eHbA1c values were significantly higher than the measured HbA1c values. The median difference was 0.75 % (95 % CI 0.40-1.10 %, P for the difference is <0.001) in the CRF group, 0.80 % (95 % CI 0.30-1.65 %, P for the difference is 0.041) in the HD group, 0.90 % (95 % CI 0.90-1.30 %, P for the difference is 0.028) in the HM group, and 0.85 % (95 % CI 0.40-1.50 %, P for the difference is 0.009) in the CLD group. We found that the measured HbA1c values were lower than the eHbA1c values in each of the groups.

[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.

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

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.

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

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...

HbA1c levels in individuals heterozygous for hemoglobin variants.

Science.gov (United States)

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

2017-04-01

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

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.

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.

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

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.

[Sensitivity, specificity, and predictive values of the level of hemoglobin, hematocrit and platelet count as an activity index in ulcerative colitis].

Science.gov (United States)

Ibarra-Rodríguez, J Jesús; Santiago-Luna, Ernesto; Velázquez-Ramírez, Gabriela Abigail; López-Ramírez, María Karina Lizbeth; Fuentes-Orozco, Clotilde; Cortés-Flores, Ana Olivia; González-Ojeda, Alejandro

2005-01-01

Ulcerative colitis (UC) is a disease characterized by relapsing and remitting non-infectious inflammation of the colorectal mucosa. Its heterogeneity makes assessment of the disease's activity a prerequisite for a rational choice of therapy. We aimed to determine sensitivity, specificity, positive and negative predictive values of hemoglobin, hematocrit, and platelets to develop a simplified activity index of UC. Sixty patients with UC were included and submitted to measurements of hemoglobin, hematocrit, and platelets, as well as sigmoidoscopy and biopsy. Sensitivity and specificity, positive and negative predictive values were correlated with the reported degree of activity in the biopsy. Kruskal-Wallis test was used to determine differences between groups, and Pearson and Spearman rank tests were used to correlate each parameter with the degree of activity. A p value hemoglobin level was 51% and 100% for hematocrit, respectively, 51% and 100% for hematocrit, and 84% and 100% for platelet counts. Spearman's correlation for hemoglobin was r = -0.866 (p hematocrit r = -0.864 (p Hemoglobin and hematocrit are useful to catalog the degree of activity of UC when it is severe. Platelet count may be a marker of severity at any time, due to its high sensitivity and specificity as a diagnostic test.

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.

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

Science.gov (United States)

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

2013-01-01

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

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

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Peng Chen

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

Radioprotective properties of some heterocyclic nitrogenous compounds against changes in hemoglobin concentration and hematocrit value in x-irradiated mice

International Nuclear Information System (INIS)

Rousdhy, H.; Pierotti, T.; Polverelli, M.

1969-01-01

Radioprotective properties of imidazole and benzimidazole have been proved in previous works. In this study, authors try to demonstrate radioprotective action of these compounds in comparison with cysteamine upon the hematopoietic system after lethal X-irradiation. Results show: no drastic variations of hematologic constants (hemoglobin concentration and hematocrit value) after intraperitoneal injection of radioprotective compounds apart certain apparent reactions with the heterocyclic compounds; the better radioprotective action of benzimidazole. Twenty five days after irradiation, hemoglobin concentration and hematocrit of radio protected mice return to normal values. (author) [fr

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.

[Analysis of Cut-off Value in Screening of Thalassemia by Capillary Hemoglobin Electrophoresis for Pregnant Women from Shenzhen Region of China].

Science.gov (United States)

Huo, Mei; Wu, Wen-Yuan; Liu, Mei; Gan, Zhi-Biao; Mao, Wei-Yu; Lin, Rong-Yao; Liu, Ai-Qin; He, Gui-Rong

2016-04-01

To investigate the cut-off value in screening of thalassemia in pregnant women from Shenzhen region by capillary hemoglobin electrophoresis. The data of capillary hemoglobin electrophoresis and genetic diagnosis of thalassemia from 2122 examined prenatal women were retrospectively analyzed. Capillary hemoglobin electrophoresis and α-, β- genetic diagnosis of thalassemia were carried out for every woman. Hemoglobin electrophoresis was performed using Capillarys 2 full-automated electrophoresis instrument. Gap polymerase chain reaction and reverse dot blot were used for genetic diagnosis of thalassemia genotyping test. The cut-off value in screening of thalassemia was determined by receiver operating characteristic curve and next to analyze the value of HbA2 and HbF in screening of thalassemia using the decided cut-off value. The areas under the curve (AUC(Roc)) of HbA2 for diagnosis of α-, β- thalassemia were 0.75 and 0.981 respectively, and the AUC(Roc) of HbF for diagnosis of β-thalassemia was 0.787. When HbA2 ≤ 2.55 was taken as the cut-off value of HbA2 for diagnosis of α-thalassemia, the sensitivity, specificity, positive likelihood ratio (LR(+)) and negative likelihood ratio (LR(-)) were 89.5%, 54.8%, 1.98, 0.19 respectively. When HbA2 ≥3.9 was taken as the cut off value of HbA2 for diagnosis of β-thalassemia, the sensitivity, specificity, LR(+) and LR(-) were 96.1%, 99.8% 480.5, 0.04 respectively. When HbF ≥0.75 was taken as the cut off value of HbF for diagnosis of β-thalassemia, the sensitivity, specificity, LR(+) and LR(-) were 83.6%, 61.8% respectively. The cut-off value in screening of thalassemia by capillarys 2 full automated electrophoresis instrument is different from that of the traditional method of hemoglobin electrophoresis, such as cellulose acetate membrane electrophoresis and agarose gel electrophoresis. Each laboratory should establish their own respective cut off value.

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.

The Added Value of Oral Glucose Tolerance Testing in Pre-Diabetes

NARCIS (Netherlands)

Luijf, Yoeri M.; Hermanides, Jeroen; Serlie, Mireille J.; Hoekstra, Joost B.; Soeters, Maarten R.

2011-01-01

With the increased acceptance of glycated hemoglobin measurement as the test of choice for the diagnosis and detection of diabetes, doubts which surround the use of the oral glucose tolerance test (OGTT) in detecting disturbances in glucose levels have become even more apparent. Metabolically, there

Clinical value of hemoglobin and its association with hepatocyte steatosis in chronic hepatitis B patients

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WANG Peng

2017-07-01

Full Text Available :ObjectiveTo investigate the clinical value of hemoglobin and its association with hepatocyte steatosis in chronic hepatitis B (CHB patients. MethodsA retrospective analysis was performed for the clinical and pathological data of 1580 CHB patients who were hospitalized in The First People′s Hospital of Shunde from January 2006 to December 2014 and underwent liver biopsy, among whom 216 (13.67% had hepatocyte steatosis (hepatocyte steatosis group and 1364 had no hepatocyte steatosis (non-hepatocyte steatosis group. The patients were divided into groups 1, 2, and 3 according to hemoglobin level, and the clinical and pathological features were analyzed and compared between the three groups. The t-test was used for comparison of continuous data between group; a one-way analysis of variance was used for comparision between multiple groups. The Mann-Whitney U test was used for ranked data between groups. The Kruskal-wallis H test was used for ranked data between multiple groups; the chi-square test was used for comparison of categorical data between groups. Spearman correlation analysis was also performed to determine the correlation between two variables. Univariate logistic regression analysis and multivariate stepwise regression analysis were used to identify the influencing factors for hepatocyte steatosis. ResultsBody mass index (BMI, systolic pressure, diastolic pressure, uric acid, total cholesterol, low-density lipoprotein, and HBV DNA load increased with the increase in hemoglobin level (F=12718,3024,4026,4624,38276,28108,7358, all P＜0.05. The incidence rates of hepatocyte steatosis in groups 1, 2, and 3 were 7.59%, 1176%,and 21.67%, respectively (χ2=44.23, P＜0.05. Hemoglobin was positively correlated with hepatic steatosis (rs=0.211, P＜0001. The multivariate logistic regression analysis showed that hemoglobin (odds ratio ［OR］=1.066, P＜0.05, BMI (OR=1576, P＜005, age (OR=1.041, P＜0.05, sex

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.

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

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

Science.gov (United States)

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

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

Directory of Open Access Journals (Sweden)

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.

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

Science.gov (United States)

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

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.

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

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

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.   

Postoperative hemoglobin level in patients with femoral neck fracture.

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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.

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.

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.

Decreasing the critical value of hemoglobin required for physician notification reduces the rate of blood transfusions

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Larson EA

2016-06-01

Full Text Available Eric A Larson,1 Paul A Thompson,1,2 Zachary K Anderson,3 Keith A Anderson,4 Roxana A Lupu,1 Vicki Tigner,5 Wendell W Hoffman6,7 1Department of Internal Medicine, 2Department of Pediatrics, Sanford School of Medicine, University of South Dakota, Sioux Falls, SD, 3Department of Internal Medicine, Fairview Health Services, Edina, MN, 4Department of Laboratory Medicine, Sanford School of Medicine, University of South Dakota, 5Medical Staff Services, 6Department of Infectious Disease, Sanford Health, Sanford USD Medical Center, 7Department of Infectious Disease, Sanford School of Medicine, University of South Dakota, Sioux Falls, SD, USAAbstract: Red blood cell transfusions have been cited as one of the most overused therapeutic interventions in the USA. Excessively aggressive transfusion practices may be driven by mandatory physician notification of critical hemoglobin values that do not generally require transfusion. We examined the effect of decreasing the critical value of hemoglobin from 8 to 7 g/dL at our institution. Along with this change, mandatory provider notification for readings between 7 and 8 g/dL was rescinded. Transfusion rates were compared retrospectively during paired 5-month periods for patients presenting in three key hemoglobin ranges (6.00–6.99, 7.00–7.99, and 8.00–8.99 g/dL. A change in transfusion practices was hypothesized in the 7–8 g/dL range, which was no longer labeled critical and for which mandated physician calls were rescinded. Transfusion rates showed a statistically significant 8% decrease (P≤0.0001 during the 5-month period post change in our transfusion practices. This decrease in the 7.00–7.99 g/dL range was significantly greater than the 2% decrease observed in either the 6–6.99 g/dL (P=0.0017 or 8–8.99 g/dL (P≤0.0001 range. Cost savings of up to $700,000/year were extrapolated from our results showing 491 fewer units of red blood cells transfused during the 5-month post change. These cost

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

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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

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.

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.

Modification of hemoglobin level and hematocrit value in the peripheral blood of mice after 45Ca internal irradiation by MPG (2-mercaptopropionylglycine)

International Nuclear Information System (INIS)

Bhagat, R.M.; Kumar, A.

1986-01-01

Radioprotective effect of MPG has been studied on the hemoglobin level and hematocrit value of peripheral blood of Swiss albino mice against radiation-induced changes after injecting radiocalcium ( 45 Ca) at the dose level of 37 kBq/g body weight. MPG was injected 15-30 minutes before 45 Ca injection at dose of 20 mg/kg body weight intraperitoneally and also MPG was injected at various repeated doses. It has been observed that MPG in repeated doses is effective in reducing the radiation-induced changes in the hemoglobin and hematocrit value of peripheral blood of Swiss albino mice following 45 Ca internal irradiation. (author)

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.

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

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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.

Hemoglobin levels in normal Filipino pregnant women.

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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.

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...

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

Science.gov (United States)

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.

70-year old female patient with mismatch between hematocrit and hemoglobin values: the effects of cold agglutinin on complete blood count.

Science.gov (United States)

Ercan, Serif; Calışkan, Mustafa; Koptur, Erhan

2014-01-01

There are a number of pre-analytical and analytical factors, which cause false results in the complete blood count. The present case identifies cold agglutinins as the cause for the mismatch between hematocrit and hemoglobin values. 70-year old female patient had a history of cerebrovascular diseases and rheumatoid arthritis. During routine laboratory examination, the patient had normal leukocyte and platelet counts; however, the hemoglobin (Hb: 105 g/L) and hematocrit (HCT: 0.214 L/L) results were discordant. Hemolysis, lipemia and cold agglutinin were evaluated as possible reasons for the mismatch between hematocrit and hemoglobin values. First blood sample was slightly hemolysed. Redrawn sample without hemolysis or lipemia was analyzed but the mismatch became even more distinct (Hb: 104 g/L and HCT: 0.08 L/L). In this sample, the titration of the cold agglutinin was determined and found to be positive at 1:64 dilution ratios. After an incubation of the sample at 37°C for 2 hours, reversibility of agglutination was observed. We conclude that cold agglutinins may interfere with the analysis of erythrocyte and erythrocyte-related parameters (HCT, MCV, MCH and MCHC); however, Hb, leukocyte and platelet counts are not affected.

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.

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...

Capillary versus Venous Hemoglobin Determination in the Assessment of Healthy Blood Donors

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Patel, Abhilasha J.; Wesley, Robert; Leitman, Susan F.; Bryant, Barbara J.

2013-01-01

Background and Objectives To determine the accuracy of fingerstick hemoglobin assessment in blood donors, the performance of a portable hemoglobinometer (HemoCue Hb 201+) was prospectively compared with that of an automated hematology analyzer (Cell-Dyn 4000). Hemoglobin values obtained by the latter were used as the “true” result. Material and Methods Capillary fingerstick samples were assayed by HemoCue in 150 donors. Fingerstick samples from two sites, one on each hand, were obtained from a subset of 50 subjects. Concurrent venous samples were tested using both HemoCue and Cell-Dyn devices. Results Capillary hemoglobin values (HemoCue) were significantly greater than venous hemoglobin values (HemoCue), which in turn were significantly greater than venous hemoglobin values by Cell-Dyn (mean ± SD: 14.05 ± 1.51, 13.89 ± 1.31, 13.62 ± 1.23, respectively; phemoglobin screening criteria (≥12.5 g/dL) by capillary HemoCue, but were deferred by Cell-Dyn values (false-pass). Five donors (3%) were deferred by capillary sampling, but passed by Cell-Dyn (false-fail). Substantial variability in repeated fingerstick HemoCue results was seen (mean hemoglobin 13.72 vs. 13.70 g/dL, absolute mean difference between paired samples 0.76 g/dL). Hand dominance was not a factor. Conclusions Capillary samples assessed via a portable device yielded higher hemoglobin values than venous samples assessed on an automated analyzer. False-pass and false-fail rates were low and acceptable in the donor screening setting, with “true” values not differing by a clinically significant degree from threshold values used to assess acceptability for blood donation. PMID:23294266

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

Science.gov (United States)

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.

Science.gov (United States)

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.

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

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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.

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.

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

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.

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)

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

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.

Quantifying risk of penile prosthesis infection with elevated glycosylated hemoglobin.

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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.

Hemoglobin C disease

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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 ...

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.

Prognostic value of hemoglobin concentrations in patients with advanced head and neck cancer treated with combined radio-chemotherapy and surgery

International Nuclear Information System (INIS)

Wagner, W.; Hermann, R.; Koch, O.; Hartlapp, J.; Krech, R.

2000-01-01

Purpose: Hemoglobin levels are currently the focus of interest as prognostic factors in patients with head and neck cancer. Most published clinical trials have confirmed hemoglobin to process a significant influence on survival in patients treated with radiotherapy. In our study we have investigated the prognostic value of hemoglobin in a combined modality schedule. Patients and Methods: Forty-three patients with advanced head and neck tumors were treated with combined radiochemotherapy. The therapy comprised 2 courses of induction chemotherapy with ifosfamide (1,500 mg/m 2 , day 1 to 5) and cisplatin (60 mg/m 2 , day 5) followed by hyperfractionated accelerated radiotherapy with a total dose of only 30 Gy. Surgery involved tumor resection and neck dissection. Results: The 1-year overall survival rate and the 2-year survival rate were 79% and 56%, respectively. The 1- and 2-year recurrence-free survival rates were 68% and 49%, respectively. Prognostic factors with an impact on survival were seen in tumor size (T3 vs T4, p=0.0088), response to radio-chemotherapy at the primary site (no vital tumor rest vs vital tumor rest, p=0.045), response to lymph node radio-chemotherapy (no vital tumor cells vs vital tumor cells, p=0.013) and level of hemoglobin after radio-chemotherapy (Hb≥11.5 g/dl vs [de

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

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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.

Radioprotective properties of some heterocyclic nitrogenous compounds against changes in hemoglobin concentration and hematocrit value in x-irradiated mice; Proprietes radioprotectrices de certains composes heterocycliques azotes sur les variations du taux d'hemoglobine et de la valeur hematocrite chez la souris irradiee

Energy Technology Data Exchange (ETDEWEB)

Rousdhy, H; Pierotti, T; Polverelli, M [Commissariat a l' Energie Atomique, Grenoble (France). Centre d' Etudes Nucleaires

1969-07-01

Radioprotective properties of imidazole and benzimidazole have been proved in previous works. In this study, authors try to demonstrate radioprotective action of these compounds in comparison with cysteamine upon the hematopoietic system after lethal X-irradiation. Results show: no drastic variations of hematologic constants (hemoglobin concentration and hematocrit value) after intraperitoneal injection of radioprotective compounds apart certain apparent reactions with the heterocyclic compounds; the better radioprotective action of benzimidazole. Twenty five days after irradiation, hemoglobin concentration and hematocrit of radio protected mice return to normal values. (author) [French] Les proprietes radioprotectrices de l'imidazole et du benzimidazole ayant ete demontrees dans de precedents travaux, les auteurs se sont attaches a etudier l'action de ces produits sur le systeme hematopofetique en comparaison avec celle de la cysteamine, apres une irradiation a dose letale. A l'aide des criteres choisis, les resultats demontrent: qu'en dehors de certaines reactions apparentes, succedant a l'injection intraperitoneale des heterocycles azotes, les constantes hematologiques (taux d'hemoglobine et valeur hematocrite) ne sont que legerement modifiees; la superiorite du benzimidazole sur les autres produits utilises. Enfin, le vingt-cinquieme jour apres irradiation, les souris protegees par les heterocycles azotes ont un taux d'hemoglobine et une valeur hematocrite tout a fait normaux. (auteur)

Hemoglobin and hematocrit values of Saudi newborns in the high altitude of Abha, Saudi Arabia

International Nuclear Information System (INIS)

Bassuni, W.; Asindi, A.A.; Mustafa, F.S.; Hassan, B.; Din, Z.S.; Kumar, R.K.

1996-01-01

A study was designed to determine the red cell values (hemoglobin and hematocrit) of neonates born in the high altitude of Abha and to compare these values with known values of other lowland areas of Saudi Arabia. From the cord blood of 587 normal, appropriate for gestational age and term infants born in 1993 in Abha Maternity Hospital, the ranges of Hb and Hct were 130 to 240 g/L and 0.24 to 0.79 L/L respectively. The mean Hb was 187 g/L. There was no significant difference between the male and female values. Also, 17% of the infants in this study were polycythemic, while no polycythemia was recorded in these lowland areas and only 2% to 4% in the general global newborn population. It was therefore revealed that Abha newborns had higher red cell values at the birth when compared to other newborns in the low altitude areas of Riyadh and Jeddah (P<0.001). We postulate that high altitude (2700 meters above sea level) of Abha, and therefore its relative hypoxia, has induced high red cell values in infants born in the city. The phenomenon therefore warrants the adoption of higher red cell reference values and not necessarily those already documented in other Saudi new born populations. (author)

Reference values of glycosylated haemoglobin and fructosamin in dogs

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Olair Carlos Beltrame

2014-09-01

Full Text Available Glycated haemoglobin and fructosamin levels are not commonly used to diagnosis Diabetes mellitus in dogs due to a lack of reference values. To estabilish the reference values and determination methods of glycated haemoglobin and frutosamine, both male and females, healthy dogs, 2-8 years old (n=100 were used. The methodologies used were the ionic resin and the kinetic method by the reduction of blue nitrotetrazolium, respectively. Medium values of glycated haemoglobin of 5.3-7.01% and 277.52-387. 30 for fructosamin established by Brazilian Diabetes Society methods can be adopted for dogs, both males and females.

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....

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.

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

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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.

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

Albumin, the major serum protein, plays a variety of functions, including binding and transporting endogenous and exogenous ligands. Its molecular structure is sensitive to different environmental modifiers, among which glucose is one of the most significant. In vivo albumin glycation occurs under physiological conditions, but it is increased in diabetes. Since bovine serum albumin (BSA) may serve as a model protein in in vitro experiments, we aimed to investigate the impact of glucose-mediated BSA glycation on the binding capacity towards gliclazide, as well as the ability of this drug to prevent glycation of the BSA molecule. To reflect normo- and hyperglycemia, the conditions of the glycation process were established. Structural changes of albumin after interaction with gliclazide (0-14 μM) were determined using fluorescence quenching and circular dichroism spectroscopy. Moreover, thermodynamic parameters as well as energy transfer parameters were determined. Calculated Stern-Volmer quenching constants, as well as binding constants for the BSA-gliclazide complex, were lower for the glycated form of albumin than for the unmodified protein. The largest, over 2-fold, decrease in values of binding parameters was observed for the sample with 30 mM of glucose, reflecting the poorly controlled diabetic state, which indicates that the degree of glycation had a critical influence on binding with gliclazide. In contrast to significant changes in the tertiary structure of BSA upon binding with gliclazide, only slight changes in the secondary structure were observed, which was reflected by about a 3% decrease of the α-helix content of glycated BSA (regardless of glucose concentration) in comparison to unmodified BSA. The presence of gliclazide during glycation did not affect its progress. The results of this study indicate that glycation significantly changed the binding ability of BSA towards gliclazide and the scale of these changes depended on glucose concentration. It

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

International Nuclear Information System (INIS)

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

Kadar Hemoglobin dan Kecerdasan Intelektual Anak

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Yuni Kusmiyati

2013-10-01

2013. Sample was taken by simple random sampling, obtained 37 students. Measuring of instruments IQ with CFQT, hemoglobin was measured using a Portable Digital Analyzer Easy Touch is a digital gauge Hb, external variable body mass index was meas- ured directly using the parameters height and weight of children. Analysis using Linear Regression. This research showed BMI was not associated with IQ (p value = 0.052. Relationship with the child’s intelligence anemia showed enough relationship (r = 0.491 and a positive pattern, where the higher levels Haemoglobin as the higher IQ score of the child’s. The coefficient of 0.241 explained 24.1 % variation anemia that is good enough to explain the variable IQ. There is a relationship between hemoglobin levels with IQ (p value = 0.002.

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.

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)

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.)

Comparison of the gold standard of hemoglobin measurement with the clinical standard (BGA) and noninvasive hemoglobin measurement (SpHb) in small children: a prospective diagnostic observational study.

Science.gov (United States)

Wittenmeier, Eva; Bellosevich, Sophia; Mauff, Susanne; Schmidtmann, Irene; Eli, Michael; Pestel, Gunther; Noppens, Ruediger R

2015-10-01

Collecting a blood sample is usually necessary to measure hemoglobin levels in children. Especially in small children, noninvasively measuring the hemoglobin level could be extraordinarily helpful, but its precision and accuracy in the clinical environment remain unclear. In this study, noninvasive hemoglobin measurement and blood gas analysis were compared to hemoglobin measurement in a clinical laboratory. In 60 healthy preoperative children (0.2-7.6 years old), hemoglobin was measured using a noninvasive method (SpHb; Radical-7 Pulse Co-Oximeter), a blood gas analyzer (clinical standard, BGAHb; ABL 800 Flex), and a laboratory hematology analyzer (reference method, labHb; Siemens Advia). Agreement between the results was assessed by Bland-Altman analysis and by determining the percentage of outliers. Sixty SpHb measurements, 60 labHb measurements, and 59 BGAHb measurements were evaluated. In 38% of the children, the location of the SpHb sensor had to be changed more than twice for the signal quality to be sufficient. The bias/limits of agreement between SpHb and labHb were -0.65/-3.4 to 2.1 g·dl(-1) . Forty-four percent of the SpHb values differed from the reference value by more than 1 g·dl(-1) . Age, difficulty of measurement, and the perfusion index (PI) had no influence on the accuracy of SpHb. The bias/limits of agreement between BGAHb and labHb were 1.14/-1.6 to 3.9 g·dl(-1) . Furthermore, 66% of the BGAHb values differed from the reference values by more than 1 g·dl(-1) . The absolute mean difference between SpHb and labHb (1.1 g·dl(-1) ) was smaller than the absolute mean difference between BGAHb and labHb (1.5 g·dl(-1) /P = 0.024). Noninvasive measurement of hemoglobin agrees more with the reference method than the measurement of hemoglobin using a blood gas analyzer. However, both methods can show clinically relevant differences from the reference method (ClinicalTrials.gov: NCT01693016). © 2015 John Wiley & Sons Ltd.

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

Science.gov (United States)

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.

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.

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

Utility of glycated albumin for the diagnosis of diabetes mellitus in a Japanese population study: results from the Kyushu and Okinawa Populaiton Study (KOPS)

Science.gov (United States)

Glycated albumin is a measure of the mean plasma glucose concentration over approximately 2-3 weeks. We determined reference values for glycated albumin, and assessed its utility for the diagnosis of type 2 diabetes mellitus in the general population. We studied 1,575 men and women (mean age, 49.9 y...

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.

Characteristics and enhanced antioxidant activity of glycated Morchella esculenta protein isolate

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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.

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.

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

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

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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.

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...

Clinical Significance of Reticulocyte Hemoglobin Content in the Diagnosis of Iron Deficiency Anemia

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Mustafa Karagülle

2013-06-01

Full Text Available OBJECTIVE: The aim of this study was to evaluate the clinical significance of reticulocyte hemoglobin content (CHr in the diagnosis of iron deficiency anemia (IDA and to compare it with other conventional iron parameters. METHODS: A total of 32 female patients with IDA (serum hemoglobin 120 g/L and serum ferritin <20 ng/mL were enrolled. RESULTS: CHr was 24.95±3.92 pg in female patients with IDA and 29.93±2.96 pg in female patients with iron deficiency. CHr showed a significant positive correlation with hemoglobin, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, serum iron, and transferrin saturation and a significant negative correlation with transferrin and total iron-binding capacity. The cut-off value of CHr for detecting IDA was 29 pg. CONCLUSION: Our data demonstrate that CHr is a useful parameter that can be confidently used in the diagnosis of IDA, and a CHr cut-off value of 29 pg predicts IDA.

Hemoglobin as an independent prognostic factor in the radiotherapy of head and neck tumors

International Nuclear Information System (INIS)

Schaefer, U.; Micke, O.; Mueller, S.B.; Schueller, P.; Willich, N.

2003-01-01

Purpose: The purpose of this study was to analyze the prognostic value of baseline hemoglobin levels before radiotherapy in patients with head and neck tumors. Patients and Methods: In a retrospective study with a median follow-up of 43 months, we analyzed the results of 214 patients irradiated for head and neck cancer between January 1, 1990 and January 1, 1998 (180 men and 34 women; median age 58 years). The treatment concept consisted in adjuvant radiotherapy in 58 patients, 77 patients received definitive radiochemotherapy, 42 patients definitive radiotherapy, and 37 patients reirradiation for in-field recurrence. Baseline hemoglobin values were divided in four groups of the same patient number (quartiles). Several known prognostic factors like sex, tumor stage, histologic grading, performance status, and treatment scheme were analyzed for their influence on overall and event-free survival and correlated with pretreatment hemoglobin values (Kaplan-Meier method). In addition, univariate und multivariate logistic regression analyses were carried out to evaluate the effect of baseline hemoglobin on response rates. Results: The median survival (event-free survival) of all patients amounted to 15 months (10 months). 25%, 50%, and 75% of patients had hemoglobin values < 11.2 g/dl, < 12.7 g/dl, and < 13.9 g/dl, respectively. In the univariate analysis, the following variables were significant prognostic factors for overall/event-free survival (log-rank test): treatment concept (p < 0.001/ p < 0.001), tumor stage (p < 0.001/p < 0.001), general condition (p < 0.001/p < 0.001), and pretreatment hemoglobin (p = 0.014/p = 0.05). Multivariate analysis (Cox) proved these parameters to be independent of each other. In addition, response rate after radiation showed a strong association between hemoglobin and local control probability (p = 0.02). Conclusion: In this retrospective analysis, baseline hemoglobin level was shown to be an independent significant prognostic factor in

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 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.

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

Is Routine Ordering of Both Hemoglobin and Hematocrit Justifiable?

Science.gov (United States)

Addison, David J.

1966-01-01

In order to assess the value of routine simultaneous hemoglobin and hematocrit determinations, paired determinations in the following groups were studied: (1) 360 consecutive pairs from the hematology laboratory, (2) 95 pairs on general medical patients, (3) 43 pairs on 10 patients with upper gastrointestinal hemorrhage, and (4) 62 pairs on 10 patients with burns. These values were plotted on scatter diagrams. In the 560 pairs only three disparate determinations were found. It is concluded that, in most clinical situations, determination of the hemoglobin or the hematocrit as a screening procedure provides as much useful information as the simultaneous determination of both. PMID:5296947

Anemia and hemoglobin levels among Indigenous Xavante children, Central Brazil.

Science.gov (United States)

Ferreira, Aline Alves; Santos, Ricardo Ventura; Souza, July Anne Mendonça de; Welch, James R; Coimbra, Carlos E A

2017-01-01

To evaluate the prevalence of anemia, mean hemoglobin levels, and the main nutritional, demographic, and socioeconomic factors among Xavante children in Mato Grosso State, Brazil. A survey was conducted with children under 10 years of age in two indigenous Xavante communities within the Pimentel Barbosa Indigenous Reserve. Hemoglobin concentration levels, anthropometric measurements, and socioeconomic/demographic data were collected by means of clinical measurements and structured interviews. The cut-off points recommended by the World Health Organization were used for anemia classification. Linear regression analyses with hemoglobin as the outcome and Poisson regression with robust variance and with the presence or absence of anemia as outcomes were performed (95%CI). Lower mean hemoglobin values were observed in children under 2 years of age, without a significant difference between sexes. Anemia was observed among 50.8% of children overall, with the highest prevalence among children under 2 years of age (77.8%). Age of the child was inversely associated with the occurrence of anemia (adjusted PR = 0.60; 95%CI 0.38-0.95) and mean hemoglobin values increased significantly with age. Greater height-for-age z-score values reduced the probability of having anemia by 1.8 times (adjusted PR = 0.59; 95%CI 0.34-1.00). Presence of another child with anemia within the household increased the probability of the occurrence of anemia by 52.9% (adjusted PR = 1.89; 95%CI 1.16-3.09). Elevated levels of anemia among Xavante children reveal a disparity between this Indigenous population and the national Brazilian population. Results suggest that anemia is determined by complex and variable relationships between socioeconomic, sociodemographic, and biological factors.

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

Science.gov (United States)

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.

Modification of postnatal hemoglobin level and hematocrit value in the peripheral blood of mice after gamma radiation in utero by MPG (2-mercaptopropionylglycine)

International Nuclear Information System (INIS)

Goyal, P.K.; Kumar, S.; Dev, P.K.

1980-01-01

Pregnant Swiss albino mice were irradiated with oamma radiation at post-conception days 14.5, 16.25 and 18.25. Hemoglobin level and hematocrit value in the peripheral blood of the male offsprings were found to be below normal during the early postnatal development. The value became normal from 4 week onwards. However these values were found to be significantly elevated in the early postnatal development of the male offsprings of the mice which were administered MPG before irradiation. The possible radioprotective mechanism of MPG is discussed. (M.G.B.)

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.

Science.gov (United States)

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.

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.

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

Science.gov (United States)

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

Science.gov (United States)

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

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

Science.gov (United States)

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.

Hematocrit and Serum Hemoglobin Do Not Influence Values in Computed Tomography Perfusion of Patients With Acute Ischemic Stroke.

Science.gov (United States)

Karwacki, Grzegorz Marek; Benz, Matthias Richard; Tyndall, Anthony Joseph; Ulmer, Stephan

There is a correlation between both serum hemoglobin (HGB) and hematocrit (HCT) and attenuation values of vessels in noncontrast-enhanced computed tomography (NECT), which could influence calculated perfusion maps in CT perfusion. We retrospectively included 45 patients, who presented with acute new neurological symptoms and underwent NECT and CT perfusion (128-row multi detector scanner, coverage: 6.9 cm craniocaudally; 80 kV; 200 mAs; temporal resolution: 2 seconds using 40 mL Ultravist 370 at a flow rate of 5 mL/s) on admission and a follow-up MRI within 1 week of admission. Hematocrit, HGB, and attenuation values did not differ between patients with stroke and controls. A statistically significant correlation was found between HCT and HGB and attenuation values in the internal carotid artery or middle cerebral artery on NECT (P Hematocrit and HGB do not influence calculated perfusion maps. There is no need for HCT/HGB-adjusted cerebral blood volume thresholds in stroke patients.

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.

Science.gov (United States)

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

Science.gov (United States)

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.

Science.gov (United States)

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

Accuracy of hemoglobin A1c imputation using fasting plasma glucose in diabetes research using electronic health records data

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Stanley Xu

2014-05-01

Full Text Available In studies that use electronic health record data, imputation of important data elements such as Glycated hemoglobin (A1c has become common. However, few studies have systematically examined the validity of various imputation strategies for missing A1c values. We derived a complete dataset using an incident diabetes population that has no missing values in A1c, fasting and random plasma glucose (FPG and RPG, age, and gender. We then created missing A1c values under two assumptions: missing completely at random (MCAR and missing at random (MAR. We then imputed A1c values, compared the imputed values to the true A1c values, and used these data to assess the impact of A1c on initiation of antihyperglycemic therapy. Under MCAR, imputation of A1c based on FPG 1 estimated a continuous A1c within ± 1.88% of the true A1c 68.3% of the time; 2 estimated a categorical A1c within ± one category from the true A1c about 50% of the time. Including RPG in imputation slightly improved the precision but did not improve the accuracy. Under MAR, including gender and age in addition to FPG improved the accuracy of imputed continuous A1c but not categorical A1c. Moreover, imputation of up to 33% of missing A1c values did not change the accuracy and precision and did not alter the impact of A1c on initiation of antihyperglycemic therapy. When using A1c values as a predictor variable, a simple imputation algorithm based only on age, sex, and fasting plasma glucose gave acceptable results.

Goal disturbance and coping in children with Type I Diabetes Mellitus : Relationships with health-related quality of life and A1C

NARCIS (Netherlands)

van Bussel, A.; Nieuwesteeg, A.M.; Janssen, E.; van Bakel, H.J.A.; Van den Bergh, B.R.H.; Maas-van Schaaijk, N.; Odink, R.; Rijk, C.H.A.M.; Hartman, E.E.

2013-01-01

Objective Our first objective was to compare the health-related quality of life (HRQoL) of children with type 1 diabetes mellitus (8–12 years) with that of a healthy reference group, and to compare glycated hemoglobin (A1C) values of these children to recommended guidelines. Our second objective was

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.

Science.gov (United States)

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.

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.

Science.gov (United States)

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

DEFF Research Database (Denmark)

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

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.

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.

A retrospective cohort study of blood hemoglobin levels in blood donors and competitive rowers

DEFF Research Database (Denmark)

Johansson, P.I.; Ullum, H.; Jensen, K.

2009-01-01

To investigate the distribution of blood hemoglobin levels in healthy blood donors and elite athletes, a retrospective cohort study from 2001 to 2005 of candidate blood donors and elite rowers in Denmark was performed. Eighty-five thousand eight hundred and forty-six blood donors were identified.......3% of the females demonstrated values above the recommended limit for athletic competition. Thus, the prevalence of a high hemoglobin value was greater in the rowers, of both gender, than in the candidate blood donors (Pblood are seen regularly in normal...... (36 962 males), and 3.9% of the males had a blood hemoglobin above 10.5 mM, equalling a hematocrit of 51% and, 1.6% of the females had hemoglobin above 9.7 mM, corresponding to a hematocrit above 47%. One thousand four hundred and six rowers (1116 males) were investigated and 10.4% of the males and 8...

Evaluation of the Efficiency of the Reticulocyte Hemoglobin Content on Diagnosis for Iron Deficiency Anemia in Chinese Adults

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Jie Cai

2017-05-01

Full Text Available Our aim was to evaluate the cut-off value and efficiency of using reticulocyte hemoglobin content as a marker to diagnose iron deficiency anemia in Chinese adults. 140 adults who needed bone marrow aspiration for diagnosis at the hematology department of the Peking Union Medical College Hospital were enrolled according to the inclusive and exclusive criteria. Venous blood samples were collected to detect complete blood count, including hemoglobin, reticulocyte hemoglobin content, hematocrit, mean cellular volume, corpuscular hemoglobin concentration, hemoglobin content, free erythrocyte protoporphyrin; iron indexes of serum ferritin, serum transferrin receptor, and unsaturated iron-binding capacity; and inflammation markers of C-reactive protein and α-acid glycoprotein. Bone marrow samples were obtained for the bone marrow iron staining, which was used as the standard for the evaluation of iron status in this study. Subjects were divided into three groups according to hemoglobin levels and bone marrow iron staining results: the IDA (iron deficiency anemia group, the NIDA (non-iron deficiency anemia group, and the control group. The differences of the above-mentioned indexes were compared among the three groups and the effect of inflammation was also considered. The cut-off value of reticulocyte hemoglobin content was determined by receiver operation curves. The IDA group (n = 56 had significantly lower reticulocyte hemoglobin content, mean cellular volume, corpuscular hemoglobin concentration, hemoglobin content, and serum ferritin; and higher free erythrocyte protoporphyrin, unsaturated iron-binding capacity, and serum transferrin receptor (p < 0.05 compared with the NIDA group (n = 38 and control group (n = 46. Hematocrit, serum ferritin, and unsaturated iron-binding capacity were significantly affected by inflammation while reticulocyte hemoglobin content and other parameters were not. The cut-off value of reticulocyte hemoglobin content for

Evaluation of the Efficiency of the Reticulocyte Hemoglobin Content on Diagnosis for Iron Deficiency Anemia in Chinese Adults.

Science.gov (United States)

Cai, Jie; Wu, Meng; Ren, Jie; Du, Yali; Long, Zhangbiao; Li, Guoxun; Han, Bing; Yang, Lichen

2017-05-02

Our aim was to evaluate the cut-off value and efficiency of using reticulocyte hemoglobin content as a marker to diagnose iron deficiency anemia in Chinese adults. 140 adults who needed bone marrow aspiration for diagnosis at the hematology department of the Peking Union Medical College Hospital were enrolled according to the inclusive and exclusive criteria. Venous blood samples were collected to detect complete blood count, including hemoglobin, reticulocyte hemoglobin content, hematocrit, mean cellular volume, corpuscular hemoglobin concentration, hemoglobin content, free erythrocyte protoporphyrin; iron indexes of serum ferritin, serum transferrin receptor, and unsaturated iron-binding capacity; and inflammation markers of C-reactive protein and α-acid glycoprotein. Bone marrow samples were obtained for the bone marrow iron staining, which was used as the standard for the evaluation of iron status in this study. Subjects were divided into three groups according to hemoglobin levels and bone marrow iron staining results: the IDA (iron deficiency anemia) group, the NIDA (non-iron deficiency anemia) group, and the control group. The differences of the above-mentioned indexes were compared among the three groups and the effect of inflammation was also considered. The cut-off value of reticulocyte hemoglobin content was determined by receiver operation curves. The IDA group ( n = 56) had significantly lower reticulocyte hemoglobin content, mean cellular volume, corpuscular hemoglobin concentration, hemoglobin content, and serum ferritin; and higher free erythrocyte protoporphyrin, unsaturated iron-binding capacity, and serum transferrin receptor ( p iron-binding capacity were significantly affected by inflammation while reticulocyte hemoglobin content and other parameters were not. The cut-off value of reticulocyte hemoglobin content for diagnosing iron deficiency anemia was 27.2 pg, with a sensitivity of 87.5% and a specificity of 92.9%. The cut-off values for

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

Science.gov (United States)

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

Science.gov (United States)

... 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.

Red cell distribution width is associated with hemoglobin A1C elevation, but not glucose elevation.

Science.gov (United States)

Bao, Xue; Wan, Min; Gu, Yeqing; Song, Yanqi; Zhang, Qing; Liu, Li; Meng, Ge; Wu, Hongmei; Xia, Yang; Shi, HongBin; Su, Qian; Fang, Liyun; Yang, Huijun; Yu, Fei; Sun, Shaomei; Wang, Xing; Zhou, Ming; Jia, Qiyu; Song, Kun; Wang, Guolin; Yu, Ming; Niu, Kaijun

2017-10-01

To investigate the association between red cell distribution width (RDW) and elevation of glucose/glycated hemoglobin (HbA1c). An analysis was conducted using data from a prospective cohort study of adults. People without prediabetes or diabetes (n=7,795) were followed for a mean of 2.90years (range: 1-7years, 95% confidence interval: 2.86-2.94years). Glucose elevation is defined as fasting glucose levels exceeding 5.6mmol/l, or 2-hour glucose values in the oral glucose tolerance test exceeding 7.8mmol/l. HbA1c elevation is defined as a HbA1c value exceeding a normal limit of 39mmol/mol (5.7%). Adjusted Cox proportional hazards regression models were used to assess the association between RDW quartiles and elevation of HbA1c/glucose. The multiple-adjusted hazard ratios (95% confidence interval) of HbA1c elevation for increased quartiles of RDW were 1.00 (reference), 1.08 (0.89, 1.30), 1.28 (1.07, 1.54), and 1.54 (1.29, 1.85) (P for trend<0.0001). However, no significant association was observed between RDW and blood glucose (fasting and postprandial). Elevated RDW is independently related to future HbA1c elevation, but not to glucose elevation. This suggests that RDW may associate with HbA1c through a non-glycemic way, which should be taken into consideration when using HbA1c as a diagnostic criterion of prediabetes or diabetes. Copyright © 2017 Elsevier Inc. All rights reserved.

Glycation of extracellular matrix proteins and its role in atherosclerosis 

Directory of Open Access Journals (Sweden)

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.

COMPARISON OF FRUCTOSAMINE AND GLYCOSYLATED HEMOGLOBIN IN A NON-INSULIN DEPENDENT DIABETIC POPULATION

Directory of Open Access Journals (Sweden)

M. Amini

1999-08-01

Full Text Available In an attempt to determine the clinical value of frnctosamine assay for monitoring type II diabetic patients, correlation of frnctosamine with glycosylated hemoglobin was studied. 100 patients with type II diabetes mcllitus were compared with 100 normal subjects. Fasting blood glucose, glycosylated hemoglobin, albumin and frnctosamine were measured in alt subjects. In the diabetic patients, a significant correlation was observed between fasting blood glucose and glycosylated hemoglobin (r = 0.64, p < 0.01 and scrum frnctosamine (r = 0.7, P < 0.01. Tlicrc was also a significant correlation between glycosylated hemoglobin and scrum frtictosmine (r = .94, I'<0.01. Frnctosamine, assay can be used as an index of diabetes control.

Maternal hemoglobin concentration and hematocrit values may affect fetus development by influencing placental angiogenesis.

Science.gov (United States)

Stangret, Aleksandra; Wnuk, Anna; Szewczyk, Grzegorz; Pyzlak, Michał; Szukiewicz, Dariusz

2017-01-01

Vasculogenesis and angiogenesis are crucial for maintaining proper placental perfusion and optimal fetal development. Among other physical and chemical factors, hypoxia is known to stimulate angiogenic processes. Preplacental type of hypoxia is often associated with maternal anemia and is thought to enhance vascularization within the fetoplacental unit. The goal of this study was to establish the correlation between the local expression of vascular endothelial growth factor (VEGF) and placenta growth factor (PlGF) receptors (flt-1, flk-1) with maternal hemoglobin (Hb) concentration, hematocrit (Ht) values and the infant birthweight. In total, 43 specimens of term placentas obtained from normal course pregnancies delivered at term were included in the study. The expression of flt-1 and flk-1 receptors was analyzed by immunohistochemical staining. Vascular/extravascular tissular index (V/EVTI) was measured by assessing a total vascular area. Nonparametric Mann-Whitney U-test and Spearman's rank correlation were used to compare the various parameters and their differences between the groups. Among the patients with low Hb concentration, nearly 2-fold greater expression of the flt-1 receptor was positively correlated with infants birthweight (p = 0.028). Increased placental vascular density (increased flt-1 expression), during a physiological course of gestation, may be an adaptive response to lowered maternal Hb concentration and Ht values encountered during pregnancy.

Hemoglobin and hematocrit at the end of hemodialysis: a better way to adjust erythropoietin dose?

Science.gov (United States)

Rangel, Erika B; Andreoli, Maria Claudia; Matos, Ana Cristina C; Guimarães-Souza, Nadia K; Mallet, Ana Cláudia; Carneiro, Fabiana D; Santos, Bento C

2010-04-01

A severe disadvantage of administration of recombinant human erythropoietin to hemodialysis patients has been reported. A significant correlation has been shown with hemoglobin values determined online by use of the blood volume monitor (BVM) and by laboratory measurement. Online hemoglobin and hematocrit were measured by use of the BVM during hemodialysis session. Data were analyzed by t test and statistical significance was defined as a P of hemoglobin and hematocrit from 11.6 +/- 1.9 to 13.9 +/- 2.4 g/dL (17.4 +/- 7.1%, P = 0.02) and from 34.4 +/- 6.8 to 42 +/- 8.3% (20.6 +/- 8.8%, P = 0.022), respectively, were observed from the beginning to the end of dialysis. We hypothesize that a new strategy for adjusting erythropoietin dose may be based on hemoglobin and hematocrit values evaluated at the end of hemodialysis, when patients are no longer hypervolemic. Inadvertent high levels of hemoglobin could be one explanation why patients present higher rates of cardiovascular and access-related events, especially when monitored online by use of the BVM to achieve the dry weight.

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

Directory of Open Access Journals (Sweden)

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.

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.

Outcome analysis of hemoglobin A1c, weight, and blood pressure in a VA diabetes education program.

Science.gov (United States)

North, Susan L; Palmer, Glen A

2015-01-01

To determine the effect of a specific diabetes education class (Basics) on hemoglobin A1c values, weight, and systolic blood pressure. In this retrospective study, the researchers compared 2 groups of male veterans with a recent diagnosis of type 2 diabetes. One group received diabetes group education (n = 175) over a 4-month period, and the other received standard diabetes management follow-up (n = 184). Outpatient clinic setting in the Midwest. Basics class compared with standard level of care. Pre- and post-laboratory values for hemoglobin A1c, weight, and systolic blood pressure. Multivariate analysis of covariance and follow-up univariate statistics for significant differences. Findings revealed significant differences in hemoglobin A1c (P education curriculum and reduction of hemoglobin A1c values. Some participants also had added benefit of significant weight loss. Published by Elsevier Inc.

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

Science.gov (United States)

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

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

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

Science.gov (United States)

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.

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.

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

Electron self-exchange in hemoglobins revealed by deutero-hemin substitution.

Science.gov (United States)

Athwal, Navjot Singh; Alagurajan, Jagannathan; Sturms, Ryan; Fulton, D Bruce; Andreotti, Amy H; Hargrove, Mark S

2015-09-01

Hemoglobins (phytoglobins) from rice plants (nsHb1) and from the cyanobacterium Synechocystis (PCC 6803) (SynHb) can reduce hydroxylamine with two electrons to form ammonium. The reaction requires intermolecular electron transfer between protein molecules, and rapid electron self-exchange might play a role in distinguishing these hemoglobins from others with slower reaction rates, such as myoglobin. A relatively rapid electron self-exchange rate constant has been measured for SynHb by NMR, but the rate constant for myoglobin is equivocal and a value for nsHb1 has not yet been measured. Here we report electron self-exchange rate constants for nsHb1 and Mb as a test of their role in hydroxylamine reduction. These proteins are not suitable for analysis by NMR ZZ exchange, so a method was developed that uses cross-reactions between each hemoglobin and its deutero-hemin substituted counterpart. The resulting electron transfer is between identical proteins with low driving forces and thus closely approximates true electron self-exchange. The reactions can be monitored spectrally due to the distinct spectra of the prosthetic groups, and from this electron self-exchange rate constants of 880 (SynHb), 2900 (nsHb1), and 0.05M(-1) s(-1) (Mb) have been measured for each hemoglobin. Calculations of cross-reactions using these values accurately predict hydroxylamine reduction rates for each protein, suggesting that electron self-exchange plays an important role in the reaction. Copyright © 2015 Elsevier Inc. All rights reserved.

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 ...

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

Science.gov (United States)

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.

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

γ irradiation of aqueous solutions of human hemoglobin in atmospheres of air and argon

International Nuclear Information System (INIS)

Puchala, M.; Szweda-Lewandowska, Z.; Leyko, W.

1979-01-01

In this study, the degrees of destruction of hemoglobin irradiated in atmospheres of air and argon were compared. Hemoglobin preparations were irradiated in the forms: oxyhemoglobin (HbO 2 ) deoxyhemoglobin (Hb 2+ ) and methemoglobin (MetHb) applying doses of 0.5 to 5 Mrad. The degree of hemoglobin destruction was estimate on the basis of changes in the values of the absorption coefficient at the Soret band, the absorption ratio A 505 /A 563 determined after conversion of irradiated preparations into MetHb, absorption coefficinets for pyridine hemochromogen obtained from irradiated preparations, and changes in parameters characterizing the hemoglobin oxygenation reaction (log p/sub 1/2/O 2 and the Hill n coefficient). The calculated oxygen enhancement ratios S were generally higher than 1 for the parameters estimated. This indicates that the presence of oxygen during irradiation enhances hemoglobin destruction

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...

A new method for detecting hemoglobin directly in whole blood using photon attenuation techniques

International Nuclear Information System (INIS)

Medhat, M.E.

2014-01-01

The objective of the proposed work is focused on measuring iron concentration directly in whole blood as tool for estimating hemoglobin and anemic conditions in patients across the world. The investigated method depends on theory of photon attenuation through transmission of low energy in whole blood sample. The mathematical expressions for calculating hemoglobin and iron deficit on blood using photon attenuation are derived. Calculations are carried out for estimating concentration of iron in blood samples taken from children, adults and old patients and therefore measuring their hemoglobin and iron deficit from normal values. Theoretical mass attenuation coefficient values were obtained using the XCOM program. A high-resolution gamma-ray spectrometry based on high purity germanium detector was employed to measure attenuation of strongly collimated monoenergetic gamma beam through blood samples. (author)

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.

In vivo integrated photoacoustic and confocal microscopy of hemoglobin oxygen saturation and oxygen partial pressure.

Science.gov (United States)

Wang, Yu; Hu, Song; Maslov, Konstantin; Zhang, Yu; Xia, Younan; Wang, Lihong V

2011-04-01

We developed dual-modality microscope integrating photoacoustic microscopy (PAM) and fluorescence confocal microscopy (FCM) to noninvasively image hemoglobin oxygen saturation (sO₂) and oxygen partial pressure (pO₂) in vivo in single blood vessels with high spatial resolution. While PAM measures sO₂ by imaging hemoglobin optical absorption at two wavelengths, FCM quantifies pO₂ using phosphorescence quenching. The variations of sO₂ and pO₂ values in multiple orders of vessel branches under hyperoxic (100% oxygen) and normoxic (21% oxygen) conditions correlate well with the oxygen-hemoglobin dissociation curve. In addition, the total concentration of hemoglobin is imaged by PAM at an isosbestic wavelength.

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.

Estimation of biological variation and reference change value of glycated hemoglobin (HbA(1c)) when two analytical methods are used.

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Ucar, Fatma; Erden, Gonul; Ginis, Zeynep; Ozturk, Gulfer; Sezer, Sevilay; Gurler, Mukaddes; Guneyk, Ahmet

2013-10-01

Available data on biological variation of HbA1c revealed marked heterogeneity. We therefore investigated and estimated the components of biological variation for HbA1c in a group of healthy individuals by applying a recommended and strictly designed study protocol using two different assay methods. Each month, samples were derived on the same day, for three months. Four EDTA whole blood samples were collected from each individual (20 women, 9 men; 20-45 years of age) and stored at -80°C until analysis. HbA1c values were measured by both high performance liquid chromatography (HPLC) (Shimadzu, Prominence, Japan) and boronate affinity chromatography methods (Trinity Biotech, Premier Hb9210, Ireland). All samples were assayed in duplicate in a single batch for each assay method. Estimations were calculated according to the formulas described by Fraser and Harris. The within subject (CV(I))-between subject (CV(G)) biological variations were 1.17% and 5.58%, respectively for HPLC. The calculated CV(I) and CV(G) were 2.15% and 4.03%, respectively for boronate affinity chromatography. Reference change value (RCV) for HPLC and boronate affinity chromatography was 5.4% and 10.4% respectively and individuality index of HbA(1c) was 0.35 and 0.93 respectively. This study for the first time described the components of biological variation for HbA1c in healthy individuals by two different assay methods. Obtained findings showed that the difference between CV(A) values of the methods might considerably affect RCV. These data regarding biological variation of HbA(1c) could be useful for a better evaluation of HbA(1c) test results in clinical interpretation. Copyright © 2013 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Non-invasive hemoglobin monitoring.

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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.

Determination of Human Hemoglobin Derivatives.

Science.gov (United States)

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

2015-01-01

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

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 ...

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

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

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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.

Patterns of glycemic control using glycosylated hemoglobin in diabetics.

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Kahlon, Arunpreet Singh; Pathak, Rambha

2011-07-01

Till now estimation of blood glucose is the highly effective method for diagnosing diabetes mellitus but it provides a short-term picture of control. More evidence is required to prove that plasma glucose and glycosylated hemoglobin levels together gives a better estimate of glycemic control and compliance with treatment. Indian diabetes risk score (IDRS) is a simplified screening tool for identifying undiagnosed diabetic subjects, requires minimum time, and effort and can help to considerably reduce the costs of screening. To study patterns of glycemic control using glycosylated hemoglobin in diabetic patients. To find out correlation between levels of plasma glucose and glycosylated hemoglobin in diabetics and to calculate IDRS of the study population. A cross sectional study was conducted among 300 known diabetic patients attending outpatient department of a rural medical college in Haryana, India. Following standard procedures and protocols FPG and glycosylated hemoglobin were measured to find out a pattern of glycemic control in them after taking their written and informed consent. A correlation between the levels of glycosylated hemoglobin and fasting blood glucose was also calculated. These patients were made to fill a performa and their demographic and clinical risk factors were noted and based on this, their IDRS was calculated. This was done to validate the IDRS in Indian rural population. Fifty-two percent of the population had fasting plasma glucose level between 125-150 mg/dl, 21% had this level between 151-175 mg/dl. Thirteen percent of the study subjects had HbA1C between 6.5-7.5, more than half (57.3%) had this value between 7.5-8.5, 12% and 18% had values between 8.5-9.5 and 9.5-10.5, respectively. Twelve percent of the participants had HbA1C level higher than 10.5. Correlation of fasting plasma glucose level and HbA1C was also studied and found that correlation coefficient came out to be .311. This correlation was found to be statistically

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.

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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

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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

Fructosamine and Hemoglobin A1c Correlations in HIV-Infected Adults in Routine Clinical Care: Impact of Anemia and Albumin Levels

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Luisa Duran

2015-01-01

Full Text Available Fructosamine is an alternative method to hemoglobin A1c (HbA1c for determining average glycemia. However, its use has not been extensively evaluated in persons living with HIV (PLWH. We examined the relationship between HbA1c and fructosamine values, specifically focusing on anemia (which can affect HbA1c and albumin as a marker of liver disease. We included 345 PLWH from two sites. We examined Spearman rank correlations between fructosamine and HbA1c and performed linear test for trends to compare fructosamine and HbA1c correlations by hemoglobin and albumin quartiles. We examined discrepant individuals with values elevated only on one test. We found a correlation of 0.70 between fructosamine and HbA1c levels. Trend tests for correlations between fructosamine and HbA1c were significant for both albumin (p=0.05 and hemoglobin (p=0.01 with the lowest correlations in the lowest hemoglobin quartile. We identified participants with unremarkable HbA1c values but elevated fructosamine values. These discrepant individuals had lower mean hemoglobin levels than those elevated by both tests. We demonstrated a large correlation between HbA1c and fructosamine across a range of hemoglobin and albumin levels. There were discrepant cases particularly among those with lower hemoglobin levels. Future studies are needed to clarify the use of fructosamine for diabetes management in PWLH.

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

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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

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...

Antithrombin activity, platelet count, hemoglobin concentration and hematocrit value determined immediately before vaginal delivery among healthy women.

Science.gov (United States)

Morikawa, Mamoru; Yamada, Takashi; Yamada, Takahiro; Koyama, Takahiro; Akaishi, Rina; Ishikawa, Satoshi; Takeda, Masamitsu; Nishida, Ryutaro; Araki, Naoto; Minakami, Hisanori

2012-08-01

To determine the normal reference values for antithrombin (AT) activity, platelet count (Plt), hemoglobin concentration (Hb), and hematocrit value (Ht) immediately before vaginal delivery among healthy pregnant women with singleton pregnancies and to determine association of these blood parameters with fetal growth. A complete blood count was performed and the AT activity was examined in 300 consecutive women admitted to hospital at > or = gestational week 36 for labor pains and/or the rupture of fetal membranes. All the women were normotensive and had singleton pregnancies, and none of the women had proteinuria, a weekly weight gain > or = 0.5 kg, or other specific complications upon admission. All the women attempted a vaginal delivery. The medians (5th-95th percentile) were 90% (71-110%) for AT activity, 234x10(9)/L (150-337x10(9)/L) for Plt, 11.0 g/dL (9.5-12.8 g/dL) for Hb, and 34.0% (30.4-38.6%) for Ht. Women with an Hb value of > or = the median (11.0 g/dL) gave birth to significantly smaller infants than their counterparts. A considerable number of healthy women exhibit a reduced AT activity and/or platelet count immediately before delivery. Hemoconcentration evidenced by a raised Hb value adversely effects on infant growth. Our data may be helpful when considering the normal ranges of these blood parameters for healthy parturient women.

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

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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.

Effect of ethanol of the radiation sensitivity of human hemoglobin

International Nuclear Information System (INIS)

Szweda-Lewandowska, Z.; Puchala, M.

1981-01-01

Radiation sensitivity of oxy-, deoxy-, and methemoglobin (HbOs, Hbbj, and MetHb) in water solutions containing 0.2 M ethanol and in ethanol-free solutions was compared. Radiation sensitivity was estimated on the basis of changes in absorbance at the Soret band (a = 430 nm for deoxyhemoglobin), changes in the absorbance ration Avqv/Avwt determined after conversion of irradiated preparations to methemoglobin, and changes in the value of parameters describing the reaction of hemoglobin oxygenation. The protection coefficient p of hemoglobin by ethanol (ratio of a change in the absence of ethanol to that in its presence) calculated from changes in absorbance at the Soret band equaled about 1.5 at a 4-Mrad dose in all bases except MetHb irradiated in air for which p was much higher (about 3.2). The protection coefficient p' calculated from Dtx values for changes in Avchemically bondv/Avwt equaled 2.2 for HbOs, and 2.8 for MetHb for preparations irradiated in air; p' = 1.7 for Hbbj and 1.8 for MetHb for preparations irradiated under argon. On the basis of these results, the role of /sup ./OH radicals and oxygen in the radiation damage of hemoglobin is discussed

Oxygen Association-Dissociation and Stability Analysis on Mouse Hemoglobins with Mutant α- and β-Globins

Science.gov (United States)

D'Surney, S. J.; Popp, R. A.

1992-01-01

Oxygen association-dissociation and hemoglobin stability analysis were performed on mouse hemoglobins with amino acid substitutions in an α-globin (α89, His to Leu) and a β-globin (β59, Lys to Ile). The variant α-globin, designated chain 5(m) in the Hba(g2) haplotype, had a high oxygen affinity and was stable. The variant β-globin, (β(s2)) of the Hbb(s2) haplotype, also had an elevated oxygen affinity and in addition was moderately unstable in 19% isopropanol. Hemoglobins from the expected nine (Hba(g2)/Hba(g2);Hbb(s)/Hbb(s) X Hba(a)/Hba(a);Hbb(s2)/Hbb(s2)) F(2) genotypes can be grouped into five classes of P(50) values characterized by strict additivity and dependency on mutant globin gene dosage; physiologically, both globin variants gave indistinguishable effects on oxygen affinity. The hemoglobin of normal mice (Hba(a)/Hba(a);Hbb(s)/Hbb(s)) had a P(50) = 40 mm Hg and the hemoglobin of Hba(g2)/Hba(g2);Hbb(s2)/Hbb(s2) F(2) mice had a P(50) = 25 mm Hg (human P(50) = 26 mm Hg). Peripheral blood from Hba(g2)/Hba(g2);Hbb(s)/Hbb(s), Hba(a)/Hba(a);Hbb(s2)/Hbb(s2) and Hba(g2)/Hba(g2);Hbb(s2)/Hbb(s2) mice exhibited normal hematological values except for a slightly higher hematocrit for Hba(g2)/Hba(g2);Hbb(s)/Hbb(s) and Hba(g2)/Hba(g2);Hbb(s2)/Hbb(s2) mice, slightly elevated red cell counts for mice of the three mutant genotypes, and significantly lower values for the mean corpuscular volume and mean corpuscular hemoglobin for Hba(g2)/Hba(g2);Hbb(s2)/Hbb(s2) mice. PMID:1427042

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

Science.gov (United States)

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

High affinity hemoglobin and Parkinson's disease.

Science.gov (United States)

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

Science.gov (United States)

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

International Nuclear Information System (INIS)

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.)

Effect of periodontal therapy on type 2 diabetes mellitus patients with chronic periodontitis with the evaluation of HbA1c

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Manvi Chandra Agarwal

2016-01-01

Full Text Available Context: In the recent years, a two-way correlation has been postulated between periodontitis and systemic conditions. One such condition is diabetes mellitus (DM. Several studies have demonstrated a close relationship between DM and chronic periodontitis. Aims: To assess the effect of periodontal therapy and scaling and root planing (SRP on the metabolic control in type 2 DM patients with chronic periodontitis based on the estimation of glycated hemoglobin (HbA1c. Settings and Design: A prospective, comparative, clinical study was performed on 50 patients suffering from type 2 DM with moderate, generalized chronic periodontitis. The study period was 6 months. Type 2 moderately controlled diabetic patients with glycated hemoglobin values within the range of 6-8% were selected. Patients with major diabetic complications, history of any antibiotic intake or periodontal treatment within the last 4 months, and smoking habits were excluded. Materials and Methods: The parameters recorded were gingival index (GI, plaque index (PI, sulcus bleeding index (SBI, probing pocket depth (PPD, clinical attachment level (CAL, and glycated hemoglobin. The recordings were done at baseline and 6 months after scaling and root planing procedures. HbA1c was measured by NycoCard Reader. Statistical Analysis Used: Karl-Pearson coefficient test, Z-test, and paired t-test. Results: Reductions in all the clinical parameters were observed and were found to be statistically significant (P < 0.005. Conclusions: Scaling and root planing resulted in a statistically significant reduction in the clinical parameters and HbA1c. So, periodontal treatment should be included in the management of diabetic patients.

Haematological values for captive harpy eagle (Harpia harpyja

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Marcos J. Oliveira

2014-08-01

Full Text Available Decreasing of harpy eagle (Harpia harpyja populations in natural environments, mainly in non-preserved areas, makes captive population management an important contribution to genetic diversity conservation. The aim of this study is to evaluate hematological parameters for captive harpy eagles maintained at the wild animals breeding center of Itaipu Binacional, Paraná State, Brazil. Fourteen blood samples from nine harpy eagles were collected from animals of both sexes, of different ages and with no clinical signs of disease. Significant variations were found in haematological values of hematocrit, hemoglobin, mean corpuscular hemoglobin (MCH, mean corpuscular hemoglobin concentration (MCHC, leukocyte, a relative number of heterophils, absolute and relative number of lymphocytes, monocytes, eosinophils, basophils and plasma protein between groups of young (less than six months old and adult birds. Comparing males and females there was variation in the values of erythrocytes, hemoglobin, mean corpuscular volume (MCV, mean corpuscular hemoglobin (MCH on heterophils, absolute and relative number of lymphocytes, eosinophils and basophils. There was also variation in the values of red blood cells, hematocrit, hemoglobin, mean corpuscular volume (MCV, mean corpuscular hemoglobin (MCH, mean corpuscular hemoglobin concentration (MCHC, leukocyte count, absolute number of lymphocytes, eosinophils and basophils among birds that study compared to another reference birds. Due to the limited information available on harpy eagle hematology, this study will be useful to the clinical assessment of birds maintained in captivity.

Comparative and quantitative determination of total hemoglobin concentration in normal and psoriatic patients

International Nuclear Information System (INIS)

Mahesar, S.M.; Dahot, M.U.; Khuhawar, M.Y.; Mahesar, H.U.

2004-01-01

The cyanmethaemoglobin technique is now recommended as the standard method by International Committee for Standardization in Hematology and British Standards Institution 1966. The hemoglobin is treated with reagent containing potassium ferricyanide, Potassium cyanide and potassium dihydrogen phosphate. The ferricyanide forms methamoglobin which is converted to cyanmethaemoglobin by the cyanide. The average values of hemoglobin, percent determined from the blood samples of normal and psoriatic (n=44) males and (n=35) females were 15.0, 12.7, 13.6 and 11.2 g/100ml. The decrease in hemoglobin concentration could be due to anemia resulting during the cell proliferation epidermis in inflammatory state and Keratolytic disorder which take place in psoriasis. (author)

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.

Delivery of iron-fortified yoghurt, through a dairy value chain program, increases hemoglobin concentration among children 24 to 59 months old in Northern Senegal: A cluster-randomized control trial.

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Le Port, Agnes; Bernard, Tanguy; Hidrobo, Melissa; Birba, Ousmane; Rawat, Rahul; Ruel, Marie T

2017-01-01

Innovative strategies are needed to enhance the nutritional impact of agriculture. Value chain approaches, which use supply chains to add value (usually economic) to products as they move from producers to consumers, can be used to increase access to nutritious foods and improve nutritional status. This study tested whether a dairy value chain could be used to distribute a micronutrient-fortified yoghurt (MNFY) (conditional upon the producer supplying a minimum amount of cow milk/day) to improve hemoglobin and reduce anemia among preschool children in a remote area in Northern Senegal. A cluster randomized control trial was used to compare 204 children (24 to 59 months of age at baseline) from households who received the MNFY coupled to a behavior change communication (BCC) campaign focusing on anemia prevention to 245 children from a control group (receiving BCC only) after one year. Randomization was done at the level of the family concession (households from the same family) (n = 321). Eligible households had a child of the target age and were willing to deliver milk to the dairy factory. Changes in anemia and hemoglobin between groups were assessed using mixed regression models. Anemia prevalence was very high at baseline (80%) and dropped to close to 60% at endline, with no differences between intervention groups. Hemoglobin increased by 0.55 g/dL, 95%CI (0.27; 0.84) more in the intervention compared to the control group after one year, in models that controlled for potentially confounding factors. The impact was greater (0.72 g/dL, 95%CI (0.34; 1.12)) for boys, compared to girls (0.38 g/dL, 95%CI (-0.03; 0.80)). The dairy value chain was a successful strategy to distribute MNFY among pastoralists in Northern Senegal, and increase Hb concentrations among their children. This study is one of the first proofs of concept showing that a nutrition-sensitive agriculture value chain approach can contribute to improved child nutrition in a remote pastoralist

[Noninvasive total hemoglobin monitoring based on multiwave spectrophotometry in obstetrics and gynecology].

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Pyregov, A V; Ovechkin, A Iu; Petrov, S V

2012-01-01

Results of prospective randomized comparative research of 2 total hemoglobin estimation methods are presented. There were laboratory tests and continuous noninvasive technique with multiwave spectrophotometry on the Masimo Rainbow SET. Research was carried out in two stages. At the 1st stage (gynecology)--67 patients were included and in second stage (obstetrics)--44 patients during and after Cesarean section. The standard deviation of noninvasive total hemoglobin estimation from absolute values (invasive) was 7.2 and 4.1%, an standard deviation in a sample--5.2 and 2.7 % in gynecologic operations and surgical delivery respectively, that confirms lack of reliable indicators differences. The method of continuous noninvasive total hemoglobin estimation with multiwave spectrophotometry on the Masimo Rainbow SET technology can be recommended for use in obstetrics and gynecology.

Patterns of glycemic control using glycosylated hemoglobin in diabetics

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Arunpreet Singh Kahlon

2011-01-01

Full Text Available Aim : Till now estimation of blood glucose is the highly effective method for diagnosing diabetes mellitus but it provides a short-term picture of control. More evidence is required to prove that plasma glucose and glycosylated hemoglobin levels together gives a better estimate of glycemic control and compliance with treatment. Indian diabetes risk score (IDRS is a simplified screening tool for identifying undiagnosed diabetic subjects, requires minimum time, and effort and can help to considerably reduce the costs of screening. Objective : To study patterns of glycemic control using glycosylated hemoglobin in diabetic patients. To find out correlation between levels of plasma glucose and glycosylated hemoglobin in diabetics and to calculate IDRS of the study population. Materials and Methods : A cross sectional study was conducted among 300 known diabetic patients attending outpatient department of a rural medical college in Haryana, India. Following standard procedures and protocols FPG and glycosylated hemoglobin were measured to find out a pattern of glycemic control in them after taking their written and informed consent. A correlation between the levels of glycosylated hemoglobin and fasting blood glucose was also calculated. These patients were made to fill a performa and their demographic and clinical risk factors were noted and based on this, their IDRS was calculated. This was done to validate the IDRS in Indian rural population. Results : Fifty-two percent of the population had fasting plasma glucose level between 125-150 mg/dl, 21% had this level between 151-175 mg/dl. Thirteen percent of the study subjects had HbA1C between 6.5-7.5, more than half (57.3% had this value between 7.5-8.5, 12% and 18% had values between 8.5-9.5 and 9.5-10.5, respectively. Twelve percent of the participants had HbA1C level higher than 10.5. Correlation of fasting plasma glucose level and HbA1C was also studied and found that correlation coefficient came

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.

A Microplate Assay for the Determination of Hemoglobin Concentration

National Research Council Canada - National Science Library

Frenchik, Michael D; McFaul, Steve J; Tsonev, Latchezar I

2004-01-01

... (NaOH), and converts all hemoglobin species, including COHb, to AHD within 5 min. Both protocols are carried out in cuvettes, and are, therefore, time intensive and difficult to manage when many samples are quantified. This impedes acquisition of triplicate values for each sample necessary to improve accuracy and determine statistical significance.

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

Hemoglobin levels and blood transfusion in patients with sepsis in Internal Medicine Departments.

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Muady, Gassan Fuad; Bitterman, Haim; Laor, Arie; Vardi, Moshe; Urin, Vitally; Ghanem-Zoubi, Nesrin

2016-10-13

Acute reduction in hemoglobin levels is frequently seen during sepsis. Previous studies have focused on the management of anemia in patients with septic shock admitted to intensive care units (ICU's), including aggressive blood transfusion aiming to enhance tissue oxygenation. To study the changes in hemoglobin concentrations during the first week of sepsis in the setting of Internal Medicine (IM) units, and their correlation to survival. Observational prospective study. We recorded hemoglobin values upon admission and throughout the first week of hospital stay in a consecutive cohort of septic patients admitted to IM units at a community hospital, the patients were enrolled into a prospective registry. Data on blood transfusions was also collected, we examined the correlation between hemoglobin concentrations during the first week of sepsis and survival, the effect of blood transfusion was also assessed. Eight hundred and fifteen patients (815) with sepsis were enrolled between February 2008 to January 2009. More than 20 % of them had hemoglobin levels less than 10g/dL on admission, a rate that was doubled during the first week of sepsis. Overall, 68 (8.3 %) received blood transfusions, 14 of them (20.6 %) due to bleeding. Typically, blood transfusion was given to older patients with a higher rate of malignancy and lower hemoglobin levels. While hemoglobin concentration on admission had strong correlation with in-hospital mortality (O.R-0.83 [95 % C.I. 0.74-0.92], blood transfusion was not found to be an independent predicting factor for mortality. Anemia is very common in sepsis. While hemoglobin level on admission exhibit independent correlation with survival, blood transfusion do not.

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

Science.gov (United States)

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

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

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

2016-09-01

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

Reference Values of Reticulocyte Hemoglobin Content and Their Relation With Other Indicators of Iron Status in Healthy Children.

Science.gov (United States)

López-Ruzafa, Encarnación; Vázquez-López, Maria A; Lendinez-Molinos, Francisco; Poveda-González, Juan; Galera-Martínez, Rafael; Bonillo-Perales, Antonio; Martín-González, Manuel

2016-10-01

Reticulocyte hemoglobin content (CHr) is considered an indicator of functional iron deficiency, but is understudied in children. The goals of this study are to determine the reference intervals for CHr in healthy children, and their relation with iron parameters, erythropoiesis, and individual conditions. A total of 902 children without iron deficiency, aged 1 to 11 years were analyzed in a cross-sectional study. Besides a physical examination of the subjects and a questionnaire completed by their parents, the complete blood count, serum transferrin receptor, ferritin, transferrin saturation, erythrocyte protoporphyrin, serum erythropoietin, C-reactive protein, and CHr levels were measured. Changes in CHr, iron status, and erythropoiesis at different age intervals were analyzed and linear multiple regression was used to identify the factors that determine CHr variability. Mean value obtained for CHr was 30.9±1.8 pg (P2.5-P97.5: 26.9 to 34.3 pg), but the influence of age on CHr (the values increased with age) and on the iron parameters justified the establishment of different reference ranges. In addition to age, nutritional status, hematologic measurements, reticulocytes, transferrin saturation, and erythrocyte protoporphyrin accounted for 39% of CHr variability.

Hemoglobin Kinetics and Long-term Prognosis in Heart Failure.

Science.gov (United States)

Díez-López, Carles; Lupón, Josep; de Antonio, Marta; Zamora, Elisabet; Domingo, Mar; Santesmases, Javier; Troya, Maria-Isabel; Boldó, Maria; Bayes-Genis, Antoni

2016-09-01

The influence of hemoglobin kinetics on outcomes in heart failure has been incompletely established. Hemoglobin was determined at the first visit and at 6 months. Anemia was defined according to World Health Organization criteria (hemoglobin < 13g/dL for men and hemoglobin < 12g/dL for women). Patients were classified relative to their hemoglobin values as nonanemic (both measurements normal), transiently anemic (anemic at the first visit but not at 6 months), newly anemic (nonanemic initially but anemic at 6 months), or permanently anemic (anemic in both measurements). A total of 1173 consecutive patients (71.9% men, mean age 66.8±12.2 years) were included in the study. In all, 476 patients (40.6%) were considered nonanemic, 170 (14.5%) had transient anemia, 147 (12.5%) developed new-onset anemia, and 380 (32.4%) were persistently anemic. During a follow-up of 3.7±2.8 years after the 6-month visit, 494 patients died. On comprehensive multivariable analyses, anemia (P < .001) and the type of anemia (P < .001) remained as independent predictors of all-cause mortality. Compared with patients without anemia, patients with persistent anemia (hazard ratio [HR] = 1.62; 95% confidence interval [95%CI], 1.30-2.03; P < .001) and new-onset anemia (HR = 1.39; 95%CI, 1.04-1.87, P = .03) had higher mortality, and even transient anemia showed a similar trend, although without reaching statistical significance (HR = 1.31; 95%CI, 0.97-1.77, P = .075). Anemia, especially persistent and of new-onset, and to a lesser degree, transient anemia, is deleterious in heart failure. Copyright © 2016 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

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...

Led Astray by Hemoglobin A1c

Directory of Open Access Journals (Sweden)

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

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.

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.

Diagnostic value of cystatin C for diagnosis of early renal damages in type 2 diabetic mellitus patients: The first experience in Iran

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Mitra Javanmardi

2015-01-01

Full Text Available Background: Diabetic nephropathy (DN is one of the most important complications of diabetes mellitus. Now-a-days, cystatin C (CysC is introduced as a new marker for diagnosis of renal damages; however, use of this marker in clinical laboratories is still controversial. The present study was aimed to evaluate the diagnostic value of serum CysC for early detection or monitoring treatment of kidney damages in the Kurdish people with type 2 diabetes mellitus. Materials and Methods: Glomerular filtration rate (GFR was estimated by Modification of Diet in Renal Disease formula. Serum CysC and urine microalbumin were also measured in 126 diabetic and healthy subjects. Blood glycated hemoglobin (Hb also measured in all healthy and diabetic patients. Two independent samples t-test, Mann-Whitney U-test, one-way ANOVA, and Kruskal-Wallis test, as well as Pearson/Spearman correlation coefficient statistical tests were used as appropriate. Results: Serum CysC was higher (1312.41 ng/ml in diabetic patients with GFR <60 ml/min than other subjects (993.25 ng/ml (patients with normal kidney function and healthy subjects. A borderline significant correlation between CysC and estimating GFR (rs = −0.16, P = 0.05 but highly significant with microalbumin (rs = 0.22, P = 0.014 was observed. Serum CysC sensitivity, negative and positive predictive values were 100 and 4%. Conclusion: CysC cover variation of GFR and urine microalbumin, but it cannot be used as a surrogating marker of glycated Hb. According to our results, it seems that serum CysC is a useful marker for screening of DN; but it cannot be used for monitoring of treatment in diabetic patients.

Effects of gamma irradiation on the structure and function of human hemoglobin

International Nuclear Information System (INIS)

Szweda-Lewandowska, Z.; Puchala, M.; Leyko, W.

1976-01-01

In this paper physicochemical and functional properties of irradiated aqueous hemoglobin solutions are presented. HbO 2 solutions (5 percent) were irradiated in air with doses ranging from 0.5 to 5 Mrad at the efficiency of 1 Mrad/hr. At doses exceeding 1 Mrad, coagulation of small amounts of protein was observed. Hemoglobin which remained in the solution consisted of a mixture of HbO 2 and MetHb. At doses of 4 and 5 Mrad the presence of hemochromogen was established. The appropriate hydrodynamic parameters--molecular weight, sedimentation constant, and limiting viscosity value--do not differ from the control values up to a dose of 1 Mrad. At greater doses sedimentation constants and the limiting viscosity number increase. The decrease in the values of the second virial coefficient and the electrophoretic behavior in polyacrylamide gel suggest some changes in the electric charge of the molecules. Simultaneously, a considerable part of the molecules exhibits an increased affinity for oxygen and a decreased heme--heme interaction

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

Directory of Open Access Journals (Sweden)

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.

PERBEDAAN KADAR HEMOGLOBIN METODE SIANMETHEMOGLOBIN DENGAN DAN TANPA SENTRIFUGASI PADA SAMPEL LEUKOSITOSIS

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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

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.

Reference ranges for hematocrit and blood hemoglobin concentration during the neonatal period: data from a multihospital health care system.

Science.gov (United States)

Jopling, Jeffery; Henry, Erick; Wiedmeier, Susan E; Christensen, Robert D

2009-02-01

"Reference ranges" are developed when it is impossible or inappropriate to establish "normal ranges" by drawing blood on healthy normal volunteers. Reference ranges for the hematocrit and the blood hemoglobin concentration of newborn infants have previously been reported from relatively small sample sizes by using measurement methods that now are considered outmoded. We sought to develop reference ranges for hematocrit and hemoglobin during the neonatal period (28 days) by using very large sample sizes and modern hematology analyzers, accounting for gestational and postnatal age and gender. Data were assembled from a multihospital health care system after exclusion of patients with a high likelihood of an abnormal value and those who were receiving blood transfusions. During the interval from 22 to 40 weeks' gestation, the hematocrit and blood hemoglobin concentration increased approximately linearly. For every week advance in gestational age, the hematocrit increased by 0.64% and the hemoglobin concentration increased by 0.21 g/dL. No difference was seen on the basis of gender. During the 4-hour interval after birth, hematocrit/hemoglobin values of late preterm and term neonates (35-42 weeks' gestation) increased by 3.6% +/- 0.5% (mean +/- SD), those of neonates of 29 to 34 weeks' gestation remained unchanged, and those of hematocrit/hemoglobin occurred. The figures presented herein describe reference ranges for hematocrit and blood hemoglobin concentration during the neonatal period, accounting for gestational and postnatal age.

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

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.

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.

The Relationship between Serum 25-Hydroxyvitamin D Concentration, Cardiorespiratory Fitness, and Insulin Resistance in Japanese Men

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Xiaomin Sun

2014-12-01

Full Text Available Here, we aim to investigate the independent and combined associations of serum 25-hydroxyvitamin D (25(OHD and cardiorespiratory fitness (CRF with glucose metabolism. Fasting blood samples of 107 men aged 40–79 years were analyzed for 25(OHD, glucose, insulin, glycated hemoglobin, and lipid profile. Homeostasis model assessment of insulin resistance index (HOMA-IR was calculated from the fasting concentrations of glucose and insulin. Visceral fat area (VFA was determined by magnetic resonance imaging and CRF by measuring maximal oxygen uptake. Median 25(OHD concentration was 36.3 nmol/L, while the prevalence of 25(OHD deficiency was 74.8%. Participants with high CRF had significantly lower HOMA-IR, glycated hemoglobin, and insulin values than participants with low CRF (p < 0.05. Higher 25(OHD concentration was strongly correlated with lower HOMA-IR and insulin values independent of VFA (p < 0.01 but significantly affected by CRF. In the high CRF group, participants with higher 25(OHD concentration had lower HOMA-IR values than participants with low 25(OHD concentration (p < 0.05. Higher 25(OHD and CRF are crucial for reducing insulin resistance regardless of abdominal fat. In addition, higher 25(OHD concentration may strengthen the effect of CRF on reducing insulin resistance in middle-aged and elderly Japanese men with high CRF.

[Differences between observed and estimated by hematocrit hemoglobin and its relevance in the diagnosis of anemia among coastal population in Venezuela: analysis of the second national study of human growth and development (SENACREDH)].

Science.gov (United States)

Flores-Torres, Jessica; Echeverría-Ortega, María; Arria-Bohorquez, Melissa; Hidalgo, Glida; Albano-Ramos, Carlos; Sanz, Rafael; Rodríguez-Morales, Alfonso J

2011-03-01

To evaluate the differences between the observed hemoglobin levels and those estimated based on hematocrit in the context of the 2nd National Study of Human Growth and Development of the Venezuelan Population (SENACREDH). 6,004 individuals were chosen by a probabilistic multistage cluster sampling representing 7,286,781 inhabitants from North Central Coastal area (Vargas, Carabobo, Capital District, Aragua and Miranda). Means of observed and estimated hemoglobin (hematocrit/3) were compared, using t test for related samples and linear regression. Mean difference between the values of observed and estimated hemoglobin was -0.3446 ±0.0002 (phemoglobin values. Regression models of hemoglobin on hematocrit showed an r2=0,87. In order to correct the estimation, we propose a new formula for calculating hemoglobin based on haematocrit values: estimated hemoglobin=(Haematocrit/3.135)+ 0.257. There is an overestimation of hemoglobin levels from hematocrit levels and therefore an underestimation of the prevalence of anemia; however, a high positive correlation between them was found, allowing modeling for achieving a better estimation of the hemoglobin from the hematocrit value.

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.

EFFECT OF ROSELLE (HIBISCUS SABDARIFFA ON CHANGES IN HEMOGLOBIN LEVELS IN PREGNANT WOMEN WITH ANEMIA TAKING IRON SUPPLEMENT

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Rif’atun Nisa

2017-12-01

Full Text Available Background: Anemia during pregnancy is one of the most common disorders in pregnant women in Indonesia. The Government has made efforts to overcome this problem, however, the rate of anemic mothers remains high. Rosella (Hibiscus Sabdariffa is considered able to increase the hemoglobin levels in pregnant mothers. Objective: To analyze the effect of Rosella flower extract (Hibiscus Sabdariffa on the increase of Hemoglobin level in pregnant women with anemia receiving Fe tablet. Methods: This study was a quasy experiment with pretest-posttest control group design conducted in November - December 2016 in the working area of Tlogosari Wetan Community Health Center. Forty-two participants were selected using accidental sampling, which 21 assigned in the experiment and control group. All samples were pregnant women in the second trimester suffering from anemia and receiving iron tablets. Hemoglobin levels were measured using hematology analyzer in laboratory. Independent t-test and paired t-test were used for data analysis. Results: Paired t-test obtained p-value 0.00 (<0.05, indicated that there was an increase of hemoglobin levels in both experiment and control group. The mean increase of hemoglobin levels in the control group was 0.61 gr and in the experiment group was 1.08. The hemoglobin levels in the experiment group were higher than the levels in the control group. Independent t-test obtained p-value 0.000 (<0.05 indicating that there was a significant difference of mean of hemoglobin levels between the control group and the treatment group. Conclusion: The consumption of rosella extract combined with Fe tablet showed a significant increase of hemoglobin levels compared with the consumption of Fe tablet alone. Therefore, it is suggested for midwife to use the result of this research as a evidence practice through counseling for pregnant mother about utilization of rosella extract that can increase hemoglobin level in pregnant woman with anemia.

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

Disturbance in hemoglobin metabolism and in vivo antimalarial activity of azole antimycotics

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Juan Ricardo Rodrigues

2011-02-01

Full Text Available Plasmodium parasites degrade host hemoglobin to obtain free amino acids, essential for protein synthesis. During this event, free toxic heme moieties crystallize spontaneously to produce a non-toxic pigment called hemozoin or ß-hematin. In this context, a group of azole antimycotics, clotrimazole (CTZ, ketoconazole (KTZ and fluconazole (FCZ, were investigated for their abilities to inhibit ß-hematin synthesis (IßHS and hemoglobin proteolysis (IHbP in vitro. The ß-hematin synthesis was recorded by spectrophotometry at 405 nm and the hemoglobin proteolysis was determined by SDS-PAGE 12.5%, followed by densitometric analysis. Compounds were also assayed in vivo in a malaria murine model. CTZ and KTZ exhibited the maximal effects inhibiting both biochemical events, showing inhibition of β-hematin synthesis (IC50 values of 12.4 ± 0.9 µM and 14.4 ± 1.4 µM respectively and inhibition of hemoglobin proteolysis (80.1 ± 2.0% and 55.3 ± 3.6%, respectively. There is a broad correlation to the in vivo results, especially CTZ, which reduced the parasitemia (%P of infected-mice at 4th day post-infection significantly compared to non-treated controls (12.4 ± 3.0% compared to 26.6 ± 3.7%, p = 0.014 and prolonged the survival days post-infection. The results indicated that the inhibition of the hemoglobin metabolism by the azole antimycotics could be responsible for their antimalarial effect.

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.

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.

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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

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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.

Fasting serum glucose and glycosylated hemoglobin level in obesity.

Science.gov (United States)

Das, R K; Nessa, A; Hossain, M A; Siddiqui, N I; Hussain, M A

2014-04-01

Obesity is a condition in which the body fat stores are increased to an extent which impairs health and leads to serious health consequences. The amount of body fat is difficult to measure directly, and is usually determined from an indirect measure - the body mass index (BMI). Increased BMI in obese persons is directly associated with an increase in metabolic disease, such as type 2 diabetes mellitus. This Analytical cross sectional study was undertaken to assess the relation between obesity and glycemic control of body by measuring fasting serum glucose and glycosylated hemoglobin. This study was carried out in the Department of Physiology, Mymensingh Medical College, Mymensingh from 1st July 2011 to 30th June 2012 on 120 equally divided male and female persons within the age range of 25 to 55 years. Age more than 55 years and less than 25 years and diagnosed case of Hypothyroidism, Cushing's syndrome, polycystic ovary, Antipsychotic drug user and regular steroid users were excluded. Non probability purposive type of sampling technique was used for selecting the study subjects. Measurement of body mass index was done as per procedure. Fasting serum glucose was estimated by glucose oxidase method and Glycosylated hemoglobin by Boronate Affinity method. Statistical analysis was done by SPSS (version 17.0). Data were expressed as Mean±SE and statistical significance of difference among the groups were calculated by unpaired student's 't' test and Pearson's correlation coefficient tests were done as applicable. The Mean±SE of fasting serum glucose was significant at 1% level (P value obese group of BMI. There was no significant difference of glycosylated hemoglobin level between control and study groups. But there was positive correlation within each group. Fasting serum glucose also showed a bit stronger positive correlation with BMI. Both obese male and female persons showed higher levels of fasting serum glucose and glycosylated hemoglobin. The observed positive

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.

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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.

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.

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

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.

Screening for type 2 diabetes and prediabetes in obese youth: evaluating alternate markers of glycemia - 1,5-anhydroglucitol, fructosamine, and glycated albumin.

Science.gov (United States)

Chan, Christine L; Pyle, Laura; Kelsey, Megan; Newnes, Lindsey; Zeitler, Philip S; Nadeau, Kristen J

2016-05-01

Hemoglobin A1c (HbA1c) is increasingly performed over the oral glucose tolerance test (OGTT) as the initial screening test for type 2 diabetes in youth. However, the optimal strategy for identifying type 2 diabetes in youth remains controversial. Alternate glycemic markers have been proposed as potentially useful tools for diabetes screening. We examined the relationships among fructosamine (FA), glycated albumin (GA), and 1,5-anhydroglucitol (1,5-AG) with traditional screening tests, HbA1c and OGTT. Youth 10-18 yrs, BMI ≥85th‰, and HbA1c prediabetes and diabetes. One hundred and seventeen, 62% female, 59% Hispanic, 22% White, 17% black, median 14.1 yr, and body mass index (BMI) z-score 2.3 participated. Median values of each alternate marker differed significantly between prediabetes and diabetes HbA1c and 2hG categories (p prediabetes HbA1c. Area under the receiver operating characteristic curves (ROC-AUCs) for alternate markers as predictors of prediabetes (0.5-0.66) were low; however, alternate marker ROC-AUCs for identifying diabetes (0.82-0.98) were excellent. Although the alternate markers were poor predictors of prediabetes, they all performed well predicting diabetes by 2hG and HbA1c. Whereas the usefulness of these markers for identifying prediabetes is limited, they may be useful in certain scenarios as second line screening tools for diabetes in overweight/obese youth. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Maternal and perinatal outcomes in second hemoglobin measurement in nonanemic women at first booking: effect of altitude of residence in peru.

Science.gov (United States)

Gonzales, Gustavo F; Tapia, Vilma; Fort, Alfredo L

2012-01-01

Objective. To determine changes in hemoglobin concentration at second measurements after a normal hemoglobin concentration was detected at first booking during pregnancy at low and at high altitudes. Methods. This is a secondary analysis of a large database obtained from the Perinatal Information System in Peru which includes 379,816 pregnant women and their babies from 43 maternity units in Peru. Results. Most women remained with normal hemoglobin values at second measurement (75.1%). However, 21.4% of women became anemic at the second measurement. In all, 2.8% resulted with moderate/severe anemia and 3.5% with erythrocytosis (Hb>14.5 g/dL). In all cases Hb was higher as altitude increased. Risk for moderate/severe anemia increased associated with higher gestational age at second measurement of hemoglobin, BMI anemia was observed with normal high Hb level at first booking living at moderate and high altitude, and high BMI. Conclusion. Prevalence of anemia increases as pregnancy progress, and that a normal value at first booking may not be considered sufficient as Hb values should be observed throughout pregnancy. BMI was a risk for anemia in a second measurement.

Associations of Glycemic Control With Cardiovascular Outcomes Among US Hemodialysis Patients With Diabetes Mellitus.

Science.gov (United States)

Rhee, Jinnie J; Zheng, Yuanchao; Montez-Rath, Maria E; Chang, Tara I; Winkelmayer, Wolfgang C

2017-06-07

There is a lack of data on the relationship between glycemic control and cardiovascular end points in hemodialysis patients with diabetes mellitus. We included adult Medicare-insured patients with diabetes mellitus who initiated in-center hemodialysis treatment from 2006 to 2008 and survived for >90 days. Quarterly mean time-averaged glycated hemoglobin (HbA 1c ) values were categorized into diabetes mellitus. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Antimicrobial activity and safety evaluation of peptides isolated from the hemoglobin of chickens.

Science.gov (United States)

Hu, Fengjiao; Wu, Qiaoxing; Song, Shuang; She, Ruiping; Zhao, Yue; Yang, Yifei; Zhang, Meikun; Du, Fang; Soomro, Majid Hussain; Shi, Ruihan

2016-12-05

Hemoglobin is a rich source of biological peptides. As a byproduct and even wastewater of poultry-slaughtering facilities, chicken blood is one of the most abundant source of hemoglobin. In this study, the chicken hemoglobin antimicrobial peptides (CHAP) were isolated and the antimicrobial and bactericidal activities were tested by the agarose diffusion assay, minimum inhibitory concentration (MIC) analysis, minimal bactericidal concentration (MBC) analysis, and time-dependent inhibitory and bactericidal assays. The results demonstrated that CHAP had potent and rapid antimicrobial activity against 19 bacterial strains, including 9 multidrug-resistant bacterial strains. Bacterial biofilm and NaCl permeability assays, transmission electron microscopy (TEM) and scanning electron microscopy (SEM) were further performed to detect the mechanism of its antimicrobial effect. Additionally, CHAP showed low hemolytic activity, embryo toxicity, and high stability in different temperatures and animal plasma. CHAP may have great potential for expanding production and development value in animal medication, the breeding industry and environment protection.

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

International Nuclear Information System (INIS)

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

1994-01-01

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

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.

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

2018-02-01

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

SPECTROPHOTOMETRY OF HEMOGLOBIN - ABSORPTION-SPECTRA OF RAT OXYHEMOGLOBIN, DEOXYHEMOGLOBIN, CARBOXYHEMOGLOBIN, AND METHEMOGLOBIN

NARCIS (Netherlands)

ZIJLSTRA, WG; BUURSMA, A; FALKE, HE; CATSBURG, JF

The absorptivity at 540 nm of methemoglobincyanide from rat blood was determined on the basis of iron and found to be equal to the established value for human methemoglobincyanide (11,01/mmol/cm). On this basis the absorption spectra of the common derivatives were determined for rat hemoglobin.

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

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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

Neo-Epitopes Generated on Hydroxyl Radical Modified GlycatedIgG Have Role in Immunopathology of Diabetes Type 2.

Directory of Open Access Journals (Sweden)

Sidra Islam

Full Text Available Glycoxidation plays a crucial role in diabetes and its associated complications. Among the glycoxidation agents, methylglyoxal (MG is known to have very highglycationpotential witha concomitant generation of reactive oxygen species (ROS during its synthesis and degradation. The presentstudy probes the MG and ROSinduced structural damage to immunoglobulin G (IgG and alterations in its immunogenicity in diabetes type 2 patients (T2DM. Human IgG was first glycated with MG followed by hydroxyl radical (OH• modification. Glycoxidation mediated effects on IgG were evaluated by various physicochemical techniques likeultraviolet (UV and fluorescence spectroscopy, 8-anilinonaphthalene-1-sulfonic acid (ANS binding studies, carbonyl andfree sulfhydryl groups assay, matrix assisted laser desorption ionization mass spectrometry-time of flight (MALDI-TOF, red blood cell (RBC haemolysis assay, Congored (CR staining analysis and scanning electron microscopy (SEM. The results revealed hyperchromicityin UV, advanced glycation end product (AGEspecific and ANS fluorescence, quenching in tyrosine and tryptophan fluorescence intensity,enhanced carbonyl content,reduction in free sulfhydryl groups,pronounced shift in m/z value of IgGand decrease in antioxidant activity in RBC induced haemolysis assayupon glycoxidation. SEM and CRstaining assay showed highly altered surface morphology in glycoxidised sample as compared to the native. Enzyme linked immunosorbent assay (ELISA and band shift assay were performed to assess the changes in immunogenicity of IgG upon glyoxidation and its role in T2DM. The serum antibodies derived from T2DM patients demonstrated strong affinity towards OH• treated MG glycatedIgG (OH•-MG-IgG when compared to native IgG (N-IgG or IgGs treated with MG alone (MG-IgG or OH• alone (OH•-IgG. This study shows the cumulating effect of OH• on the glycation potential of MG. The results point towards the modification of IgG in diabetes patients

New-Onset Diabetes Mellitus After Transplantation in a Cynomolgus Macaque (Macaca fasicularis).

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Matthews, Kristin A; Tonsho, Makoto; Madsen, Joren C

2015-08-01

A 5.5-y-old intact male cynomolgus macaque (Macaca fasicularis) presented with inappetence and weight loss 57 d after heterotopic heart and thymus transplantation while receiving an immunosuppressant regimen consisting of tacrolimus, mycophenolate mofetil, and methylprednisolone to prevent graft rejection. A serum chemistry panel, a glycated hemoglobin test, and urinalysis performed at presentation revealed elevated blood glucose and glycated hemoglobin (HbA1c) levels (727 mg/dL and 10.1%, respectively), glucosuria, and ketonuria. Diabetes mellitus was diagnosed, and insulin therapy was initiated immediately. The macaque was weaned off the immunosuppressive therapy as his clinical condition improved and stabilized. Approximately 74 d after discontinuation of the immunosuppressants, the blood glucose normalized, and the insulin therapy was stopped. The animal's blood glucose and HbA1c values have remained within normal limits since this time. We suspect that our macaque experienced new-onset diabetes mellitus after transplantation, a condition that is commonly observed in human transplant patients but not well described in NHP. To our knowledge, this report represents the first documented case of new-onset diabetes mellitus after transplantation in a cynomolgus macaque.

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.

Glycosylated hemoglobin testing in the National Social Life, Health, and Aging Project.

Science.gov (United States)

Gregg, Forest T; O'Doherty, Katie; Schumm, L Philip; McClintock, Martha K; Huang, Elbert S

2014-11-01

Longitudinal biomeasures of health are still new in nationally representative social science survey research. Data measuring blood sugar control provide opportunities for understanding the development of diabetes and its complications in older adults, but researchers must be aware that some of the differences across time can be due to variations in measurement procedures. This is a well-recognized issue whenever all samples cannot be assayed at the same time and we sought to present the analytic methods to quantify and adjust for the variation. We collected and analyzed HbA1C, glycated hemoglobin, a biomeasure of average blood sugar concentrations within the past few months. Improvements were made in the collection protocol for Wave 2, and assays were performed by a different lab. The HbA1C data obtained during Wave 1 and Wave 2 are consistent with the expected population distributions for differences by gender, age, race/ethnicity, and diabetes status. Age-adjusted mean HbA1C declined slightly from Wave 1 to Wave 2 by -0.19 (95% confidence interval [CI]: -0.27, -0.10), and the average longitudinal change was -0.12 (95% CI: -0.18, -0.06). Collection of HbA1C in Wave 2 permits researchers to examine the relationship between HbA1C and new health and social measures added in Wave 2, and to identify factors related to the change in HbA1C. Changes in collection protocol and labs between waves may have yielded small systematic differences that require analysts to carefully interpret absolute HbA1C values. We recommend analytic methods for cross wave differences in HbA1C and steps to ensure cross wave comparability in future studies. © The Author 2014. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Hemoglobin, red blood cell count, hematocrit and derived parameters for diagnosing anemia in elderly males

International Nuclear Information System (INIS)

Khan, Z.; Nawaz, M.

2013-01-01

Anemia is one of the most common micronutrient deficiency in our community. Nutritional anaemias are caused when there is an inadequate body store of a specific nutrient needed for hemoglobin synthesis. The most common nutrient deficiency is of iron. Therefore, a cross-sectional survey was conducted on the healthy elderly male, aged >= 40 and 77 years (n=60) volunteers in order to assess their blood parameters, such as hemoglobin concentration (Hb), hematocrit (HCT), red blood cell count (RBC), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH) and mean corpuscular hemoglobin concentration (MCHC) for the diagnosis of anemia. The demographic results showed mean values (50.10+-8.79) years for age, 66-68 +- 1.95 inches for height , 71.43 +- 6.43 kg body weight, 98.34+-0.48 degree F body temperature, 124 +- 8.67 systolic blood pressure, 82.17 +- 4.15 diastolic pressure while, The pulse rate was found to be 74.63 +- 7.02/minute. Similarly, mean values for lean body weight (LBW) found to be 49.9+-2.89, ideal body weight (IBW) 60.9 +- 4.49, body surface area (BSA) was 1.8 +- 0.1 m2 whereas, body mass index (BMI) showed mean value 24.9 +- 2.6 kg/m2. More so, overall mean Hb found to be 13.60 g/dl, RBC 4.6 mill/mm3, HCT/PCV 43%, MCV 92.95fl, MCH 29.42 pg and MCHC was found to be 31.73 g/dl. The normal range of Hb for men was 13-17 g/dl and 31.67% of the subjects participated in the study was considered to be anemic showing less Hb than normal range. The volunteers were suggested to improve the dietary habits and to take iron supplements in order to overcome the iron deficiency anemia. (author)

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.

Roles of the β 146 histidyl residue in the molecular basis of the Bohr Effect of hemoglobin: A proton nuclear magnetic resonance study

International Nuclear Information System (INIS)

Busch, M.R.; Mace, J.E.; Ho, N.T.; Ho, Chien

1991-01-01

Assessment of the roles of the carboxyl-terminal β146 histidyl residues in the alkaline Bohr effect in human and normal adult hemoglobin by high-resolution proton nuclear magnetic resonance spectroscopy requires assignment of the resonances corresponding to these residues. By a careful spectroscopic study of human normal adult hemoglobin, enzymatically prepared des(His146β)-hemoglobin, and the mutant hemoglobins Cowtown (β146His → Leu) and York (β146His → Pro), the authors have resolved some of these conflicting results. By a close incremental variation of pH over a wide range in chloride-free 0.1 M N-(2-hydroxyethyl)piperazine-N'-2-ethanesulfonic acid buffer, a single resonance has been found to be consistently missing in the proton nuclear magnetic resonance spectra of these hemoglobin variants. The results indicate that the contribution of the β146 histidyl residues is 0.52 H + /hemoglobin tetramer at pH 7.6, markedly less than 0.8 H + /hemoglobin tetramer estimated by study of the mutant hemoglobin Cowtown (β146His → Leu) by Shih and Perutz. They have found that at least two histidyl residues in the carbonmonoxy form of this mutant have pK values that are perturbed, and they suggest that these pK differences may in part account for this discrepancy. The results show that the pK values of β146 histidyl residues in the carbonmonoxy form of hemoglobin are substantially affected by the presence of chloride and other anions in the solvent, and thus, the contribution of this amino acid residue to the alkaline Bohr effect can be shown to vary widely in magnitude, depending on the solvent composition. These results demonstrate that the detailed molecular mechanisms of the alkaline Bohr effect are not unique but are affected both by the hemoglobin structure and by the interactions with the solvent components in which the hemoglobin molecule resides

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.

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

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

Directory of Open Access Journals (Sweden)

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...

Monitor hemoglobin concentration and oxygen saturation in living mouse tail using photoacoustic CT scanner

Science.gov (United States)

Liu, Bo; Kruger, Robert; Reinecke, Daniel; Stantz, Keith M.

2010-02-01

Purpose: The purpose of this study is to use PCT spectroscopy scanner to monitor the hemoglobin concentration and oxygen saturation change of living mouse by imaging the artery and veins in a mouse tail. Materials and Methods: One mouse tail was scanned using the PCT small animal scanner at the isosbestic wavelength (796nm) to obtain its hemoglobin concentration. Immediately after the scan, the mouse was euthanized and its blood was extracted from the heart. The true hemoglobin concentration was measured using a co-oximeter. Reconstruction correction algorithm to compensate the acoustic signal loss due to the existence of bone structure in the mouse tail was developed. After the correction, the hemoglobin concentration was calculated from the PCT images and compared with co-oximeter result. Next, one mouse were immobilized in the PCT scanner. Gas with different concentrations of oxygen was given to mouse to change the oxygen saturation. PCT tail vessel spectroscopy scans were performed 15 minutes after the introduction of gas. The oxygen saturation values were then calculated to monitor the oxygen saturation change of mouse. Results: The systematic error for hemoglobin concentration measurement was less than 5% based on preliminary analysis. Same correction technique was used for oxygen saturation calculation. After correction, the oxygen saturation level change matches the oxygen volume ratio change of the introduced gas. Conclusion: This living mouse tail experiment has shown that NIR PCT-spectroscopy can be used to monitor the oxygen saturation status in living small animals.

Status gizi, kadar hemoglobin, ureum, dan kreatinin pasien konseling gizi hemodialisa

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Kristiawan P. A. Nugroho

2018-01-01

Full Text Available ABSTRACTBackground : Patients who are undergoing hemodialysis therapy must know which foods that may be consumed including foods containing animal protein, low potassium, and low salt. The role of nutritionists is needed to provide nutritional counseling related to dietary adjustment. Studies that have been conducted by previous researchers are about diet from hemodialysis patients and the various factors that affect dietary compliance of patients, but no one has been studying the relation related to nutritional status, hemoglobin, ureum, and creatinine levels before and after doing a counseling that also has a relationship with diet and dietary compliance for hemodialysis patients.Objectives : To analyze the relationship of nutritional status, hemoglobin, ureum, and creatinine levels of hemodialysis patients before and after doing nutritional counseling in RSUD Ungaran. Methods : The study used a descriptive quantitaive method with one group pretest posttest design with cross sectional approach. The research was conducted in Hemodialysis Unit of RSUD Ungaran with a total sampling of 30 hemodialysis patient. Primary data were obtained from respondent’s data entry and FFQ, observation, and interviews. Secondary data were obtained from respondent’s medical records include the level of hemoglobin, urea, and cretinine. Data were analyzed using SPSS programme with Paired t Test. Results : The results of SPSS analysis showed that probability value from urea men 0,016 < 0,05 and urea women – hemoglobin men and women – creatinin men and women overall 0,000 < 0,05, which means that the average levels of those components before and after doing a nutritional counseling is different.Conclusions : A nutritional counseling indicate any change in the nutritional status of the entire hemodialysis patients, based on hemoglobin levels increased, while urea and creatinine levels decreased; but all those components are not in the normal category. Levels of

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...

THE EFFECTIVENESS OF MIXED JUICE MUNG BEAN AND GUAVA FOR INCREASING HEMOGLOBIN LEVEL IN CANCER PATIENT WITH CHEMOTHERAPY

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Nurul Huda

2016-09-01

Full Text Available Cancer is a chronic disease with high morbidity and mortality rate in a year. One of therapy in curing cancer is chemotherapy. But unfortunately chemotherapy has some negative effects such as decreasing the level of hemoglobin (Hb. Mung bean that contain a lot of iron and Guava which is rich of vitamin C for iron absorption are useful in cancer patient with chemotherapy. Therefore, a mixture of both is believed in increasing hemoglobin level significantly. The purpose of this study was to determine the effectiveness of mixed juice mung bean and guava for increasing hemoglobin level in experiment and control group of cancer patient with chemotherapy.This research used Quasi Experiment design with pretest-posttest design control group approach. The total number of respondent was 30 chosen by purposive sampling method. Results of this study showed hemoglobin level in experiment group 14.07 and 10.42 in control group with p value (0,000 < α (0,05. It can be concluded that a mixture juice mung beans and guava effective for increasing hemoglobin level in cancer patient with chemotherapy. This research suggests that this mixture can be an option for nursing intervention in increasing hemoglobin level for cancer patient after receiving chemotherapy.

Do blood tests cause anemia in hospitalized patients? The effect of diagnostic phlebotomy on hemoglobin and hematocrit levels.

Science.gov (United States)

Thavendiranathan, Paaladinesh; Bagai, Akshay; Ebidia, Albert; Detsky, Allan S; Choudhry, Niteesh K

2005-06-01

To determine whether phlebotomy contributes to changes in hemoglobin and hematocrit levels in hospitalized general internal medicine patients. Retrospective cohort study. General internal medicine inpatient service at a tertiary care hospital. All adult patients discharged from the Toronto General Hospital's internal medicine service between January 1 and June 30, 2001. A total of 989 hospitalizations were reviewed and 404 hospitalizations were included in our analysis. Mean (SD) hemoglobin and hematocrit changes during hospitalization were 7.9 (12.6) g/L (Phemoglobin and hematocrit were predicted by the volume of phlebotomy, length of hospital stay, admission hemoglobin/hematocrit value, age, Charlson comorbidity index, and admission intravascular volume status. The volume of phlebotomy remained a strong predictor of drop in hemoglobin and hematocrit after adjusting for other predictors using multivariate analysis (Phemoglobin and hematocrit of 7.0 g/L and 1.9%, respectively. Phlebotomy is highly associated with changes in hemoglobin and hematocrit levels for patients admitted to an internal medicine service and can contribute to anemia. This anemia, in turn, may have significant consequences, especially for patients with cardiorespiratory diseases. Knowing the expected changes in hemoglobin and hematocrit due to diagnostic phlebotomy will help guide when to investigate anemia in hospitalized patients.

Biochemistry Applied to Everyday Life: Chemical Equilibrium and the Transporting Function of the Hemoglobin

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Carlos Mario Echeverría Palacio

2006-12-01

Full Text Available The hemoglobin is a blood protein which cantransport oxygen, a gas insoluble in water, todifferent organs where it is required for the properfunction; this protein also transports themetabolic products, CO2 and H+ for theirexcretion. This process depends on pH, the BPGconcentration, pO2 and pCO2. The cooperativebinding between hemoglobin and those compoundsand the conformational changes necessaryfor oxygen and CO2 uptake and release inthe specific place where they are required. Abruptchanges of atmospheric pressure associatedwith height and the exposure to other gases suchas CO present in vehicles and closed roomscould compromise the normal functioning of theorganism because their presence affects thetransport function of the hemoglobin. In thispaper, we will explain everyday phenomenarelated to the transport of gases through hemoglobinas a demonstration that a knowledge ofbiochemistry begins to be useful from now on to understand everyday situations and give usan expectation of their value to comprehendmany health problems that would be faced inthe future

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 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.

Efficacy and safety of once-weekly intravenous epoetin alfa in maintaining hemoglobin levels in hemodialysis patients.

Science.gov (United States)

Locatelli, Francesco; Villa, Giuseppe; Messa, Piergiorgio; Filippini, Armando; Cannella, Giuseppe; De Ferrari, Giacomo; Naso, Agostino; Rossi, Egidio; Formica, Marco; Lombardi, Luigi; Rotolo, Ugo; Conte, Feruccio

2008-01-01

Although an erythropoiesis-stimulating agent (ESA) is most frequently administered intravenously for treatment of anemia in patients with chronic kidney disease who are on dialysis, few studies have compared the efficacy of different intravenous (i.v.) dosing schedules. This multicenter, phase IIIb, open-label, controlled study randomized 289 stable hemodialysis patients to continue with conventional dosing of i.v. epoetin alfa or darbepoetin, or to switch to once-weekly i.v. epoetin alfa at the same cumulative weekly starting dose, to maintain hemoglobin levels at 11.0-13.0 g/dL, and within 1.0 g/dL of the baseline value. Hemoglobin levels and ESA doses were recorded every 4 weeks for 28 weeks. Hemoglobin levels fell significantly and ESA doses increased significantly between baseline and week 28 (mean of week 16-28 values) in the once-weekly epoetin alfa group, compared with the conventional treatment group (phemoglobin levels between the groups was 0.73 g/dL (greater than the threshold for therapeutic equivalence of 0.5 g/dL). The changes between groups from baseline was significant at all time points for hemoglobin levels (0.36, 0.46, 0.81, 0.87, 0.78, 0.62 and 0.49 g/dL) and from week 12 for ESA dose (718.5, 1,326.5, 1,732.0, 1,839.7 and 1,959.1 IU/week; p=0.005). Hemoglobin was maintained at the target level in 78% and 84% of patients on conventional dosing, and 67% and 64% of those on once-weekly epoetin alfa in the intention-to-treat (p=0.1) and per protocol (p=0.016) populations, respectively. This study did not show therapeutic equivalence of once-weekly i.v. epoetin alfa with conventional dosing regimens.

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...

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

Science.gov (United States)

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.

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

Analysis of drug-protein binding using on-line immunoextraction and high-performance affinity microcolumns: Studies with normal and glycated human serum albumin.

Science.gov (United States)

Matsuda, Ryan; Jobe, Donald; Beyersdorf, Jared; Hage, David S

2015-10-16

A method combining on-line immunoextraction microcolumns with high-performance affinity chromatography (HPAC) was developed and tested for use in examining drug-protein interactions with normal or modified proteins. Normal human serum albumin (HSA) and glycated HSA were used as model proteins for this work. High-performance immunoextraction microcolumns with sizes of 1.0-2.0 cm × 2.1mm i.d. and containing anti-HSA polyclonal antibodies were developed and tested for their ability to bind normal HSA or glycated HSA. These microcolumns were able to extract up to 82-93% for either type of protein at 0.05-0.10 mL/min and had a binding capacity of 0.34-0.42 nmol HSA for a 1.0 cm × 2.1mm i.d. microcolumn. The immunoextraction microcolumns and their adsorbed proteins were tested for use in various approaches for drug binding studies. Frontal analysis was used with the adsorbed HSA/glycated HSA to measure the overall affinities of these proteins for the drugs warfarin and gliclazide, giving comparable values to those obtained previously using similar protein preparations that had been covalently immobilized within HPAC columns. Zonal elution competition studies with gliclazide were next performed to examine the specific interactions of this drug at Sudlow sites I and II of the adsorbed proteins. These results were also comparable to those noted in prior work with covalently immobilized samples of normal HSA or glycated HSA. These experiments indicated that drug-protein binding studies can be carried out by using on-line immunoextraction microcolumns with HPAC. The same method could be used in the future with clinical samples and other drugs or proteins of interest in pharmaceutical studies or biomedical research. Copyright © 2015 Elsevier B.V. All rights reserved.

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.

Ability of the Masimo pulse CO-Oximeter to detect changes in hemoglobin.

Science.gov (United States)

Colquhoun, Douglas A; Forkin, Katherine T; Durieux, Marcel E; Thiele, Robert H

2012-04-01

The decision to administer blood products is complex and multifactorial. Accurate assessment of the concentration of hemoglobin [Hgb] is a key component of this evaluation. Recently a noninvasive method of continuously measuring hemoglobin (SpHb) has become available with multi-wavelength Pulse CO-Oximetry. The accuracy of this device is well documented, but the trending ability of this monitor has not been previously described. Twenty patients undergoing major thoracic and lumbar spine surgery were recruited. All patients received radial arterial lines. On the contralateral index finger, a R1 25 sensor (Rev E) was applied and connected to a Radical-7 Pulse CO-Oximeter (both Masimo Corp, Irvine, CA). Blood samples were drawn intermittently at the anesthesia provider's discretion and were analyzed by the operating room satellite laboratory CO-Oximeter. The value of Hgb and SpHb at that time point was compared. Trend analysis was performed by the four quadrant plot technique, testing directionality of change, and Critchley's polar plot method testing both directionality and magnitude of the change in values. Eighty-eight samples recorded at times of sufficient signal quality were available for analysis. Four quadrant plot analysis revealed 94% of data within the quadrants associated with the correct direction change, and 90% of data points lay within the analysis bounds proposed by Critchley. Pulse CO-Oximetry offers an acceptable trend monitor in patients undergoing major spine surgery. Future work should explore the ability of this device to detect large changes in hemoglobin, as well as its applicability in additional surgical and non-surgical patient populations.

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

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

2017-07-01

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

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...

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

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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.

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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.

The Prognostic Value of Hemoglobin Concentration in Postoperative Radiotherapy of 835 Patients With Laryngeal Cancer

International Nuclear Information System (INIS)

Rutkowski, Tomasz; Suwinski, Rafal; Idasiak, Adam

2007-01-01

Purpose: To investigate the prognostic value of hemoglobin (Hb) concentration in patients with laryngeal cancer treated with postoperative radiotherapy (pRT). Methods and Materials: The records of 835 patients who underwent pRT between 1980 and 2003 were reviewed. Most patients (526 of 835 patients; 63%) were in advanced clinical stages (T3-T4) and 371 of 835 patients (44%) were node positive. Total laryngectomy had been performed in 676 of 835 patients (81%). Median Hb concentration before (Hb0) and after pRT (Hb1) was the same (13.3 g/dl). However, individual differences between Hb1 and Hb0 (dHb) varied within a broad range (-8.8; 5.0 g/dl). Univariate and multivariate analyses were performed to identify variables significantly associated with locoregional control (LRC), metastases-free survival, and overall survival. Results: Patients with dHb greater than 0 had significantly improved 5-year LRC compared with those with dHb of 0 or less (80% vs. 72%, p = 0.01). Conversely, when categorized, neither Hb0 nor Hb1 had a significant influence on LRC. In multivariate analysis, dHb remained a prognostic factor for LRC (p = 0.01) among the other variables, which included overall radiation treatment time and nodal status. None of the Hb-related variables significantly influenced metastases-free or overall survival. Conclusion: Individual change in Hb concentration during the course of pRT (dHb) rather than Hb level before or after pRT appeared as an independent prognostic factor for LRC in this set of patients

Oxidative stress in preeclampsia and the role of free fetal hemoglobin

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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.

[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.

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

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)

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.

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

A microcalorimetry and binding study on interaction of dodecyl trimethylammonium bromide with wigeon hemoglobin

International Nuclear Information System (INIS)

Bordbar, A.K.; Moosavi-Movahedi, A.A.; Amini, M.K.

2003-01-01

The thermodynamic parameters for the binding of dodecyl trimethylammonium bromide (DTAB) with wigeon hemoglobin (Hb) in aqueous solution at various pH and 27 deg. C have been measured by equilibrium dialysis and titration microcalorimetry techniques. The Scatchard plots represent unusual features at neutral and alkaline pH and specific binding at acidic pH. This leads us to analyze the binding data by fitting the data to the Hill equation for multiclasses of binding sites. The best fit was obtained with the equation for one class at acidic pH and two classes at neutral and alkaline pH. The thermodynamic analysis of the binding process shows that the strength of binding at neutral pH is more than these at other pH values. This can be related to the more accessible hydrophobic surface area of wigeon hemoglobin at this pH. The endothermic enthalpy data which was measured by microcalorimetry confirms the binding data analysis and represents the more regular and stable structure of wigeon hemoglobin at neutral pH

Perbandingan Zat Besi dengan dan Tanpa Vitamin C terhadap Kadar Hemoglobin Wanita Usia Subur

Directory of Open Access Journals (Sweden)

Tuti Anggriani Utama

2013-03-01

only iron. Intervention is the provision of iron with and without vitamin C, one capsule a week.Mean of hemoglobin level in control group before intervention was 9.15 gram/dL increased to 10.19 gram/dL in after intervention. Treatment group also show increasing hemoglobin level mean before and after intervention from 9.5 gram/dL to 11.44 gram/dL. Paired T test revealed significant differences between control and treatment group (p value = 0.000. It is hoped this research can be used as one input and evaluation of nutrition programs planning to do in order to improve healthy lifestyles of women workers at PT Sarana Mandiri Mukti Kapahiang.

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.

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

Iron stores in 70-year-old Danish men and women. Evaluation in 469 individuals by serum ferritin and hemoglobin

DEFF Research Database (Denmark)

Milman, N; Schultz-Larsen, K

1994-01-01

Iron status, including serum (S-) ferritin and hemoglobin (Hb) was assessed in a population survey of 469 old subjects (70 years of age; 254 men, 215 women); 7.9% of the participants had abnormal laboratory tests indicating diseases which might be connected with inappropriately high S-ferritin le......Iron status, including serum (S-) ferritin and hemoglobin (Hb) was assessed in a population survey of 469 old subjects (70 years of age; 254 men, 215 women); 7.9% of the participants had abnormal laboratory tests indicating diseases which might be connected with inappropriately high S......-ferritin levels. Men had a median S-ferritin of 114 micrograms/L, 5-95 percentile 28-373 micrograms/L; 2.4% had values depleted iron stores), 3.5% values from 15-30 micrograms/L (i.e., small iron stores), and 94.1% values > 30 micrograms/L (e.g., replete iron stores); 74.4% had values...

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

A Multifunctional Bread Rich in Beta Glucans and Low in Starch Improves Metabolic Control in Type 2 Diabetes: A Controlled Trial.

Science.gov (United States)

Tessari, Paolo; Lante, Anna

2017-03-17

Functional foods may be useful for people with diabetes. The soluble fibers beta glucans can modify starch digestion and improve postprandial glucose response. We analyzed the metabolic effects of a specifically designed 'functional' bread, low in starch, rich in fibers (7 g/100 g), with a beta glucan/starch ratio of (7.6:100, g/g), in people with type 2 diabetes mellitus. Methods : Clinical and metabolic data from two groups of age-, sex- and glycated hemoglobin-matched diabetic subjects, taking either the functional bread or regular white bread, over a roughly six-month observation period, were retrieved. Bread intake did not change during the trial. The functional bread reduced glycated hemoglobin by ~0.5% (absolute units) vs. pre-treatment values ( p = 0.028), and by ~0.6% vs. the control group ( p = 0.027). Post-prandial and mean plasma glucose was decreased in the treatment group too. Body weight, blood pressure and plasma lipids did not change. The acceptance of the functional bread was good in the majority of subjects, except for taste. A starch-restricted, fiber-rich functional bread, with an increased beta glucan/starch ratio, improved long term metabolic control, and may be indicated in the dietary treatment of type 2 diabetes.

Multidisciplinary Treatment of the Metabolic Syndrome Lowers Blood Pressure Variability Independent of Blood Pressure Control.

Science.gov (United States)

Marcus, Yonit; Segev, Elad; Shefer, Gabi; Sack, Jessica; Tal, Brurya; Yaron, Marianna; Carmeli, Eli; Shefer, Lili; Margaliot, Miri; Limor, Rona; Gilad, Suzan; Sofer, Yael; Stern, Naftali

2016-01-01

Blood pressure (BP) variability (BPV) contributes to target organ damage independent of BP. The authors examined the effect of a 1-year multidisciplinary intervention on BPV in patients with the metabolic syndrome (MetS) as defined by criteria from the Third Report of the Adult Treatment Panel. Forty-four nondiabetic patients underwent clinical and biochemical profiling, 24-hour ambulatory BP monitoring (ABPM), body composition, carotid intima-media thickness, and carotid-femoral pulse wave velocity (PWV). The intervention targeted all MetS components. BPV was assessed by the standard deviation of daytime systolic BP derived from ABPM. Patients with low and high BPV (lower or higher than the median daytime standard deviation of 11.6 mm Hg) did not differ in regards to systolic and diastolic BP, age, fasting glucose, glycated hemoglobin, and body mass index, but the high-variability group had higher values of low-density lipoprotein and leg fat. The 1-year intervention resulted in weight reduction but not BP-lowering. BPV declined in the high-variability group in association with lowering of PWV, C-reactive protein, glycated hemoglobin, alanine aminotransferase, asymmetric dimethylarginine, and increased high-density lipoprotein cholesterol. A multidisciplinary intervention independent of BP-lowering normalized BPV, lowered PWV, and enhanced metabolic control. © 2015 Wiley Periodicals, Inc.

A Multifunctional Bread Rich in Beta Glucans and Low in Starch Improves Metabolic Control in Type 2 Diabetes: A Controlled Trial

Science.gov (United States)

Tessari, Paolo; Lante, Anna

2017-01-01

Design: Functional foods may be useful for people with diabetes. The soluble fibers beta glucans can modify starch digestion and improve postprandial glucose response. We analyzed the metabolic effects of a specifically designed ‘functional’ bread, low in starch, rich in fibers (7 g/100 g), with a beta glucan/starch ratio of (7.6:100, g/g), in people with type 2 diabetes mellitus. Methods: Clinical and metabolic data from two groups of age-, sex- and glycated hemoglobin-matched diabetic subjects, taking either the functional bread or regular white bread, over a roughly six-month observation period, were retrieved. Results: Bread intake did not change during the trial. The functional bread reduced glycated hemoglobin by ~0.5% (absolute units) vs. pre-treatment values (p = 0.028), and by ~0.6% vs. the control group (p = 0.027). Post-prandial and mean plasma glucose was decreased in the treatment group too. Body weight, blood pressure and plasma lipids did not change. The acceptance of the functional bread was good in the majority of subjects, except for taste. Conclusions: A starch-restricted, fiber-rich functional bread, with an increased beta glucan/starch ratio, improved long term metabolic control, and may be indicated in the dietary treatment of type 2 diabetes. PMID:28304350

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

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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.

Cationic composition and acid-base state of the extracellular fluid, and specific buffer value of hemoglobin from the branchiopod crustacean Triops cancriformis.

Science.gov (United States)

Pirow, Ralph; Buchen, Ina; Richter, Marc; Allmer, Carsten; Nunes, Frank; Günsel, Andreas; Heikens, Wiebke; Lamkemeyer, Tobias; von Reumont, Björn M; Hetz, Stefan K

2009-04-01

Recent insights into the allosteric control of oxygen binding in the extracellular hemoglobin (Hb) of the tadpole shrimp Triops cancriformis raised the question about the physico-chemical properties of the protein's native environment. This study determined the cationic composition and acid-base state of the animal's extracellular fluid. The physiological concentrations of potential cationic effectors (calcium, magnesium) were more than one order of magnitude below the level effective to increase Hb oxygen affinity. The extracellular fluid in the pericardial space had a typical bicarbonate concentration of 7.6 mM but a remarkably high CO(2) partial pressure of 1.36 kPa at pH 7.52 and 20 degrees C. The discrepancy between this high CO(2) partial pressure and the comparably low values for water-breathing decapods could not solely be explained by the hemolymph-sampling procedure but may additionally arise from differences in cardiovascular complexity and efficiency. T. cancriformis hemolymph had a non-bicarbonate buffer value of 2.1 meq L(-1) pH(-1). Hb covered 40-60% of the non-bicarbonate buffering power. The specific buffer value of Hb of 1.1 meq (mmol heme)(-1) pH(-1) suggested a minimum requirement of two titratable histidines per heme-binding domain, which is supported by available information from N-terminal sequencing and expressed sequence tags.

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

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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

IS HEMOGLOBIN E GENE WIDELY SPREAD IN THE STATE OF MADHYA PRADESH IN CENTRAL INDIA? EVIDENCE FROM FIVE TYPICAL FAMILIES

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R S Balgir

2014-09-01

Full Text Available Background: Red cell inherited hemoglobin anomalies are commonly encountered in the central region of India. These cause a public health concern due to high degree of morbidity, mortality, and fetal loss in the backward, underprivileged, and vulnerable people. Purpose: To report five typical families of hemoglobin E disorders identified for the first time in the state of Madhya Pradesh from central India. Methods: Out of a total of 445 couples/families (excluding the present study with 1526 persons (848 males and 678 females referred from a tertiary hospital in central India for investigations of anemia/hemoglobinopathies during the period from March 2010 to February 2014, we came across five typical rare couples/families of hemoglobin E disorders worthy of detailed investigations. Laboratory investigations were carried out following the standard procedures after cross checking for quality control from time to time. Results: For the first time, we have encountered nine cases of heterozygous hemoglobin E trait, two members with hemoglobin E-β-thalassemia (double heterozygosity, two cases of sickle cell-hemoglobin E disease (double heterozygosity, and none with homozygous hemoglobin E. Cases  of hemoglobin E trait, hemoglobin E-β-thalassemia, sickle cell-β-thalassemia and sickle cell-E disease showed moderate to severe anemia, and target cells, and reduced values of red cell indices like RBC, Hb level, HCT, MCV, MCH and MCHC, representing abnormal hematological profile and clinical manifestations before blood transfusion. Conclusions: Double heterozygosity for hemoglobinopathies such as occurrence of β-thalassemia mutation with structurally abnormal hemoglobins (Hb S and Hb E is a rare entity, but occurs with severe clinical manifestations only in those areas or communities where these are highly prevalent, testifying the migrations and genetic admixture. Distribution of hemoglobin E and β-thalassemia in different districts of Madhya Pradesh

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

Hemoglobin, hematocrit, and changes in cerebral blood flow: the Second Manifestations of ARTerial disease-Magnetic Resonance study.

Science.gov (United States)

van der Veen, Pieternella H; Muller, Majon; Vincken, Koen L; Westerink, Jan; Mali, Willem P T M; van der Graaf, Yolanda; Geerlings, Mirjam I

2015-03-01

Hemoglobin and hematocrit are important determinants of blood viscosity and arterial oxygen content and may therefore influence cerebral blood flow (CBF). We examined cross-sectional and prospective associations of hemoglobin and hematocrit with CBF in 569 patients with manifest arterial disease (mean age 57 ± 10 years) with available data on magnetic resonance angiography to measure parenchymal CBF. Mean (SD) parenchymal CBF at baseline was 52.3 (9.8) mL/min/100 mL and decreased with 1.5 (11.0) mL/min/100 mL after on average 3.9 years of follow-up. Linear regression analyses showed that greater hemoglobin and hematocrit values were associated with lower baseline parenchymal CBF and more decline in parenchymal CBF over time, independent of cardiovascular risk factors, use of antiplatelet drugs, anticoagulants, or diuretics, and brain measures: adjusted mean differences (95% confidence interval [CI]) in decline in parenchymal CBF between patients in the lower and upper quartiles of hemoglobin and hematocrit were -2.48 (95% CI -3.70 to -1.25) and -3.69 (95% CI -5.45 to -1.94) mL/min/100 mL. Higher hemoglobin and hematocrit were associated with lower baseline parenchymal CBF and a greater decline in parenchymal CBF over time, possibly as a result of physiological compensating mechanisms. Copyright © 2015 Elsevier Inc. All rights reserved.

Investigations of immunoglobulins, circulating immune complexes and plasma free hemoglobin in cancer patients on 60Co gamma-ray therapy

International Nuclear Information System (INIS)

Horvath, M.; Rode, I.L.; Fekete, B.; Kiss, B.; Ringwald, G.

1981-01-01

32 patients with different tumours were irradiated by 60 Co gamma-rays. During therapy lasting for several weeks, changes in the content of immunoglobulin and of some other serum proteins, circulating immune complexes and plasma free hemoglobin were determined. Immunosuppression according to immunoglobulin content in serum was not produced by this type of radiation. Decrease in immune complex levels was a good prognostic sign. Low values of plasma hemoglobin content during treatment indicated that no erythrocyte membrane damage had been effected. (orig.) [de

Diabetes mellitus defined by hemoglobin A1c value: Risk characterization for incidence among Japanese subjects in the JPHC Diabetes Study.

Science.gov (United States)

Kato, Masayuki; Takahashi, Yoshihiko; Matsushita, Yumi; Mizoue, Tetsuya; Inoue, Manami; Kadowaki, Takashi; Tsugane, Shoichiro; Noda, Mitsuhiko

2011-10-07

Aims/Introduction:  Although several risk factors for type 2 diabetes have been identified, most of them have been identified in studies on Western populations, and they should be evaluated in a Japanese population. In 2010, new diagnostic criteria for diabetes mellitus using hemoglobin A1c (HbA1c) were released and its use in epidemiological studies has many advantages. The aim of the present study was to evaluate risk factors for type 2 diabetes defined based on HbA1c values in a Japanese population.   A total of 9223 subjects (3076 men and 6147 women) were followed up for 5 years. Diabetes was defined based on self-report or HbA1c value. Risk factors for diabetes were evaluated as odds ratios adjusted for potential confounding factors by logistic regression.   During the 5-year follow-up period, we documented 518 incident cases of diabetes (232 men and 286 women). Of the 518 incident cases, 310 cases were diagnosed by HbA1c alone. Among the men, age, smoking (both past smoking and current smoking) and family history of diabetes significantly increased the risk of diabetes. Among the women, body mass index, family history of diabetes and hypertension significantly increased the risk of diabetes. These results did not change markedly after adjustment for the baseline HbA1c values, and the baseline HbA1c value itself was a significant risk factor for diabetes mellitus.   Known risk factors for diabetes established in Western populations also increased the risk of diabetes in a Japanese population defined on the basis of HbA1c values. (J Diabetes Invest, doi: 10.1111/j.2040-1124.2011.00119.x, 2011).

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

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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.

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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.