Quantifying risk of penile prosthesis infection with elevated glycosylated hemoglobin.

PubMed

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.

Association of hemoglobin values at booking with adverse maternal outcomes among Peruvian populations living at different altitudes.

PubMed

Gonzales, Gustavo F; Tapia, Vilma; Gasco, Manuel; Carrillo, Carlos E; Fort, Alfredo L

2012-05-01

To determine hemoglobin values associated with adverse maternal outcomes among Peruvian populations at different altitudes. A retrospective cohort study was conducted using data from the Perinatal Information System. Adverse maternal outcomes were assessed. Risk of pre-eclampsia increased at maternal hemoglobin levels above 14.5 g/dL (OR 1.27; 95% CI, 1.18-1.36) or below 7.0 g/dL (OR 1.52; CI 95%, 1.08-2.14). Altitude above 2000 m reduced risk (OR 0.65; 95% CI 0.62-0.68). Risk of postpartum hemorrhage (PPH) increased with moderate/severe anemia (OR 6.15; 95% CI, 3.86-9.78) and at moderate altitudes (OR 1.26; 95% CI, 1.12-1.43). Mild anemia at any altitude was associated with reduced risk of pre-eclampsia (OR 0.85, 95% CI, 0.81-0.89) and PPH (OR 1.01; 95% CI, 0.88-1.15). Risk of premature rupture of membranes was reduced at high hemoglobin values. Maternal mortality increased at hemoglobin levels below 9.0 g/dL (OR 5.68; 95% CI, 2.97-10.80) and above 14.5 g/dL (OR 2.18; 95% CI, 1.22-3.91). Maternal mortality increased at moderate altitudes (OR 29.2; 95% CI, 2.62-324.60) and high altitudes (OR 66.4; 95% CI, 6.65-780.30) when hemoglobin levels were below 9.0 g/dL. Elevated altitude and hemoglobin levels influence maternal outcomes. Copyright © 2012 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

Noninvasive Assessment of Excessive Erythrocytosis as a Screening Method for Chronic Mountain Sickness at High Altitude.

PubMed

Vyas, Kaetan J; Danz, David; Gilman, Robert H; Wise, Robert A; León-Velarde, Fabiola; Miranda, J Jaime; Checkley, William

2015-06-01

Vyas, Kaetan J., David Danz, Robert H. Gilman, Robert A. Wise, Fabiola León-Velarde, J. Jaime Miranda, and William Checkley. Noninvasive assessment of excessive erythrocytosis as a screening method for chronic mountain sickness at high altitude. High Alt Med Biol 16:162-168, 2015.--Globally, over 140 million people are at risk of developing chronic mountain sickness, a common maladaptation to life at high altitude (>2500 meters above sea level). The diagnosis is contingent upon the identification of excessive erythrocytosis (EE). Current best practices to identify EE require a venous blood draw, which is cumbersome for large-scale surveillance. We evaluated two point-of-care biomarkers to screen for EE: noninvasive spot-check tests of total hemoglobin and oxyhemoglobin saturation (Pronto-7, Masimo Corporation). We conducted paired evaluations of total serum hemoglobin from a venous blood draw and noninvasive, spot-check testing of total hemoglobin and oxyhemoglobin saturation with the Pronto-7 in 382 adults aged ≥35 years living in Puno, Peru (3825 meters above sea level). We used the Bland-Altman method to measure agreement between the noninvasive hemoglobin assessment and the gold standard lab hemoglobin analyzer. Mean age was 58.8 years and 47% were male. The Pronto-7 test was unsuccessful in 21 (5%) participants. Limits of agreement between total hemoglobin measured via venous blood draw and the noninvasive, spot-check test ranged from -2.8 g/dL (95% CI -3.0 to -2.5) to 2.5 g/dL (95% CI 2.2 to 2.7), with a bias of -0.2 g/dL (95% CI -0.3 to -0.02) for the difference between total hemoglobin and noninvasive hemoglobin concentrations. Overall, the noninvasive spot-check test of total hemoglobin had a better area under the receiver operating characteristic curve compared to oxyhemoglobin saturation for the identification of EE as measured by a gold standard laboratory hemoglobin analyzer (0.96 vs. 0.82; p<0.001). Best cut-off values to screen for EE with the Pronto 7 were ≥19.9 g/dL in males and ≥17.5 g/dL in females. At these cut-points, sensitivity and specificity were both 92% and 89% for males and females, respectively. A noninvasive, spot-check test of total hemoglobin had low bias and high discrimination for the detection of EE in high altitude Peru, and may be a useful point-of-care tool for large-scale surveillance in high-altitude settings.

Hemoglobin

DTIC Science & Technology

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

Proinflammatory state and circulating erythropoietin in persons with and without anemia.

PubMed

Ferrucci, Luigi; Guralnik, Jack M; Woodman, Richard C; Bandinelli, Stefania; Lauretani, Fulvio; Corsi, Anna Maria; Chaves, Paulo H M; Ershler, William B; Longo, Dan L

2005-11-01

High circulating levels of proinflammatory cytokines cause anemia, perhaps by interacting with erythropoietin production or biological activity. We characterize the relationships of systemic inflammation, erythropoietin, and hemoglobin. Data are from the InCHIANTI (Invecchiare in Chianti, aging in the Chianti area) study population. A sample of 1270 persons aged 65 years or older and 30 men and 30 women from each age-decade 20 to 70 years were randomly selected from the residents in the Chianti, Italy, geographic area. Of the 1714 eligible persons, 1235 had complete data on inflammatory markers, erythropoietin, hemoglobin, potential causes of anemia, and other relevant covariates. Anemia was defined as hemoglobin less than 12 g/dL in women and less than 13 g/dL in men. Independent of age, sex, and hemoglobin, the number of elevated inflammatory markers (C-reactive protein, interleukin-6, interleukin-1beta, and tumor necrosis factor-alpha) was associated with progressively higher erythropoietin in non-anemic participants but lower erythropoietin in anemic participants. Findings were consistent across different causes of anemia. The threshold at which the effect of inflammation on erythropoietin reversed was close to 13.0 g/dL of hemoglobin. Our findings suggest that anemia of inflammation evolves from a "pre-anemic" stage characterized by a compensatory increment of erythropoietin that maintains normal hemoglobin levels to a stage of clinically evident anemia in which erythropoietin levels are not high enough to maintain normal hemoglobin, possibly because of the inhibitory effect of inflammation on erythropoietin production. This hypothesis requires testing in a longitudinal study.

Sherpas share genetic variations with Tibetans for high-altitude adaptation.

PubMed

Bhandari, Sushil; Zhang, Xiaoming; Cui, Chaoying; Yangla; Liu, Lan; Ouzhuluobu; Baimakangzhuo; Gonggalanzi; Bai, Caijuan; Bianba; Peng, Yi; Zhang, Hui; Xiang, Kun; Shi, Hong; Liu, Shiming; Gengdeng; Wu, Tianyi; Qi, Xuebin; Su, Bing

2017-01-01

Sherpas, a highlander population living in Khumbu region of Nepal, are well known for their superior climbing ability in Himalayas. However, the genetic basis of their adaptation to high-altitude environments remains elusive. We collected DNA samples of 582 Sherpas from Nepal and Tibetan Autonomous Region of China, and we measured their hemoglobin levels and degrees of blood oxygen saturation. We genotyped 29 EPAS1 SNPs, two EGLN1 SNPs and the TED polymorphism (3.4 kb deletion) in Sherpas. We also performed genetic association analysis among these sequence variants with phenotypic data. We found similar allele frequencies on the tested 32 variants of these genes in Sherpas and Tibetans. Sherpa individuals carrying the derived alleles of EPAS1 (rs113305133, rs116611511 and rs12467821), EGLN1 (rs186996510 and rs12097901) and TED have lower hemoglobin levels when compared with those wild-type allele carriers. Most of the EPAS1 variants showing significant association with hemoglobin levels in Tibetans were replicated in Sherpas. The shared sequence variants and hemoglobin trait between Sherpas and Tibetans indicate a shared genetic basis for high-altitude adaptation, consistent with the proposal that Sherpas are in fact a recently derived population from Tibetans and they inherited adaptive variants for high-altitude adaptation from their Tibetan ancestors.

Schoolchildren with Learning Difficulties Have Low Iron Status and High Anemia Prevalence

PubMed Central

Arcanjo, C. P. C.; Santos, P. R.

2016-01-01

Background. In developing countries there is high prevalence of iron deficiency anemia, which reduces cognitive performance, work performance, and endurance; it also causes learning difficulties and negative impact on development for infant population. Methods. The study concerns a case-control study; data was collected from an appropriate sample consisting of schoolchildren aged 8 years. The sample was divided into two subgroups: those with deficient initial reading skills (DIRS) (case) and those without (control). Blood samples were taken to analyze hemoglobin and serum ferritin levels. These results were then used to compare the two groups with Student's t-test. Association between DIRS and anemia was analyzed using odds ratio (OR). Results. Hemoglobin and serum ferritin levels of schoolchildren with DIRS were statistically lower when compared to those without, hemoglobin p = 0.02 and serum ferritin p = 0.04. DIRS was statistically associated with a risk of anemia with a weighted OR of 1.62. Conclusions. In this study, schoolchildren with DIRS had lower hemoglobin and serum ferritin levels when compared to those without. PMID:27703806

Schoolchildren with Learning Difficulties Have Low Iron Status and High Anemia Prevalence.

PubMed

Arcanjo, F P N; Arcanjo, C P C; Santos, P R

2016-01-01

Background . In developing countries there is high prevalence of iron deficiency anemia, which reduces cognitive performance, work performance, and endurance; it also causes learning difficulties and negative impact on development for infant population. Methods . The study concerns a case-control study; data was collected from an appropriate sample consisting of schoolchildren aged 8 years. The sample was divided into two subgroups: those with deficient initial reading skills (DIRS) (case) and those without (control). Blood samples were taken to analyze hemoglobin and serum ferritin levels. These results were then used to compare the two groups with Student's t -test. Association between DIRS and anemia was analyzed using odds ratio (OR). Results . Hemoglobin and serum ferritin levels of schoolchildren with DIRS were statistically lower when compared to those without, hemoglobin p = 0.02 and serum ferritin p = 0.04. DIRS was statistically associated with a risk of anemia with a weighted OR of 1.62. Conclusions . In this study, schoolchildren with DIRS had lower hemoglobin and serum ferritin levels when compared to those without.

I. RENAL THRESHOLDS FOR HEMOGLOBIN IN DOGS

PubMed Central

Lichty, John A.; Havill, William H.; Whipple, George H.

1932-01-01

We use the term "renal threshold for hemoglobin" to indicate the smallest amount of hemoglobin which given intravenously will effect the appearance of recognizable hemoglobin in the urine. The initial renal threshold level for dog hemoglobin is established by the methods employed at an average value of 155 mg. hemoglobin per kilo body weight with maximal values of 210 and minimal of 124. Repeated daily injections of hemoglobin will depress this initial renal threshold level on the average 46 per cent with maximal values of 110 and minimal values of 60 mg. hemoglobin per kilo body weight. This minimal or depression threshold is relatively constant if the injections are continued. Rest periods without injections cause a return of the renal threshold for hemoglobin toward the initial threshold levels—recovery threshold level. Injections of hemoglobin below the initial threshold level but above the minimal or depression threshold will eventually reduce the renal threshold for hemoglobin to its depression threshold level. We believe the depression threshold or minimal renal threshold level due to repeated hemoglobin injections is a little above the glomerular threshold which we assume is the base line threshold for hemoglobin. Our reasons for this belief in the glomerular threshold are given above and in the other papers of this series. PMID:19870016

The influence of hydroxyurea on oxidative stress in sickle cell anemia

PubMed Central

Torres, Lidiane de Souza; da Silva, Danilo Grünig Humberto; Belini Junior, Edis; de Almeida, Eduardo Alves; Lobo, Clarisse Lopes de Castro; Cançado, Rodolfo Delfini; Ruiz, Milton Artur; Bonini-Domingos, Claudia Regina

2012-01-01

Objective The oxidative stress in 20 sickle cell anemia patients taking hydroxyurea and 13 sickle cell anemia patients who did not take hydroxyurea was compared with a control group of 96 individuals without any hemoglobinopathy. Methods Oxidative stress was assessed by thiobarbituric acid reactive species production, the Trolox-equivalent antioxidant capacity and plasma glutathione levels. Results Thiobarbituric acid reactive species values were higher in patients without specific medication, followed by patients taking hydroxyurea and the Control Group (p < 0.0001). The antioxidant capacity was higher in patients taking hydroxyurea and lower in the Control Group (p = 0.0002 for Trolox-equivalent antioxidant capacity and p < 0.0292 for plasma glutathione). Thiobarbituric acid reactive species levels were correlated with higher hemoglobin S levels (r = 0.55; p = 0.0040) and lower hemoglobin F concentrations(r = -0.52; p = 0.0067). On the other hand, plasma glutathione levels were negatively correlated with hemoglobin S levels (r = -0.49; p = 0.0111) and positively associated with hemoglobin F values (r = 0.56; p = 0.0031). Conclusion Sickle cell anemia patients have high oxidative stress and, conversely, increased antioxidant activity. The increase in hemoglobin F levels provided by hydroxyurea and its antioxidant action may explain the reduction in lipid peroxidation and increased antioxidant defenses in these individuals. PMID:23323065

Noninvasive Assessment of Excessive Erythrocytosis as a Screening Method for Chronic Mountain Sickness at High Altitude

PubMed Central

Vyas, Kaetan J.; Danz, David; Gilman, Robert H.; Wise, Robert A.; León-Velarde, Fabiola; Jaime Miranda, J.

2015-01-01

Abstract Vyas, Kaetan J., David Danz, Robert H. Gilman, Robert A. Wise, Fabiola León-Velarde, J. Jaime Miranda, and William Checkley. Noninvasive assessment of excessive erythrocytosis as a screening method for chronic mountain sickness at high altitude. High Alt Med Biol 16:162–168, 2015.—Globally, over 140 million people are at risk of developing chronic mountain sickness, a common maladaptation to life at high altitude (>2500 meters above sea level). The diagnosis is contingent upon the identification of excessive erythrocytosis (EE). Current best practices to identify EE require a venous blood draw, which is cumbersome for large-scale surveillance. We evaluated two point-of-care biomarkers to screen for EE: noninvasive spot-check tests of total hemoglobin and oxyhemoglobin saturation (Pronto-7, Masimo Corporation). We conducted paired evaluations of total serum hemoglobin from a venous blood draw and noninvasive, spot-check testing of total hemoglobin and oxyhemoglobin saturation with the Pronto-7 in 382 adults aged ≥35 years living in Puno, Peru (3825 meters above sea level). We used the Bland-Altman method to measure agreement between the noninvasive hemoglobin assessment and the gold standard lab hemoglobin analyzer. Mean age was 58.8 years and 47% were male. The Pronto-7 test was unsuccessful in 21 (5%) participants. Limits of agreement between total hemoglobin measured via venous blood draw and the noninvasive, spot-check test ranged from −2.8 g/dL (95% CI −3.0 to −2.5) to 2.5 g/dL (95% CI 2.2 to 2.7), with a bias of −0.2 g/dL (95% CI −0.3 to −0.02) for the difference between total hemoglobin and noninvasive hemoglobin concentrations. Overall, the noninvasive spot-check test of total hemoglobin had a better area under the receiver operating characteristic curve compared to oxyhemoglobin saturation for the identification of EE as measured by a gold standard laboratory hemoglobin analyzer (0.96 vs. 0.82; p<0.001). Best cut-off values to screen for EE with the Pronto 7 were ≥19.9 g/dL in males and ≥17.5 g/dL in females. At these cut-points, sensitivity and specificity were both 92% and 89% for males and females, respectively. A noninvasive, spot-check test of total hemoglobin had low bias and high discrimination for the detection of EE in high altitude Peru, and may be a useful point-of-care tool for large-scale surveillance in high-altitude settings. PMID:25973777

Convergent evolution of hemoglobin switching in jawed and jawless vertebrates.

PubMed

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.

Effects of Epoetin Alfa Titration Practices, Implemented After Changes to Product Labeling, on Hemoglobin Levels, Transfusion Use, and Hospitalization Rates.

PubMed

Molony, Julia T; Monda, Keri L; Li, Suying; Beaubrun, Anne C; Gilbertson, David T; Bradbury, Brian D; Collins, Allan J

2016-08-01

Little is known about epoetin alfa (EPO) dosing at dialysis centers after implementation of the US Medicare prospective payment system and revision of the EPO label in 2011. Retrospective cohort study. Approximately 412,000 adult hemodialysis patients with Medicare Parts A and B as primary payer in 2009 to 2012 to describe EPO dosing and hemoglobin patterns; of these, about 70,000 patients clustered in about 1,300 dialysis facilities to evaluate facility-level EPO titration practices and patient-level outcomes in 2012. Facility EPO titration practices when hemoglobin levels were <10 and >11g/dL (grouped treatment variable) determined from monthly EPO dosing and hemoglobin level patterns. Patient mean hemoglobin levels, red blood cell transfusion rates, and all-cause and cause-specific hospitalization rates using a facility-based analysis. Monthly EPO dose and hemoglobin level, red blood cell transfusion rates, and all-cause and cause-specific hospitalization rates. Monthly EPO doses declined across all hemoglobin levels, with the greatest decline in patients with hemoglobin levels < 10g/dL (July-October 2011). In 2012, nine distinct facility titration practices were identified. Across groups, mean hemoglobin levels differed slightly (10.5-10.8g/dL) but within-patient hemoglobin standard deviations were similar (∼0.68g/dL). Patients at facilities implementing greater dose reductions and smaller dose escalations had lower hemoglobin levels and higher transfusion rates. In contrast, patients at facilities that implemented greater dose escalations (and large or small dose reductions) had higher hemoglobin levels and lower transfusion rates. There were no clinically meaningful differences in all-cause or cause-specific hospitalization events across groups. Possibly incomplete claims data; excluded small facilities and those without consistent titration patterns; hemoglobin levels reported monthly; inferred facility practice from observed dosing. Following prospective payment system implementation and labeling revisions, EPO doses declined significantly. Under the new label, facility EPO titration practices were associated with mean hemoglobin levels (but not standard deviations) and transfusion use, but not hospitalization rates. Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Sun-dried cowpeas and amaranth leaves recipe improves β-carotene and retinol levels in serum and hemoglobin concentration among preschool children.

PubMed

Nawiri, Mildred P; Nyambaka, Hudson; Murungi, Jane I

2013-03-01

Vitamin A deficiency (VAD) and anemia are major challenges among children and expecting and lactating mothers in developing countries. Intervention with locally available dark green leafy vegetables (DGLV) is more sustainable to eradicate VAD, being cost-effective and readily adaptable to local communities. DGLV contain high levels of iron and β-carotene (BC) and therefore useful in fighting VAD and anemia. Since DGLVs are season-dependent sun-drying enables their availability during low seasons. However, their contribution to the bioavailability of BC and the improvement of hemoglobin are not well understood. The study therefore investigated the effect of consuming cooked recipe consisting of sun-dried amaranth and cowpea leaves on the levels of BC, retinol, and hemoglobin in preschool children from Machakos District, a semiarid region in Kenya. Vegetables were purchased from local vegetable market, with some sun-dried in an open shade. Levels of BC and retinol in serum and BC in fresh and processed vegetables were determined by a HPLC method and hemoglobin using a portable Hemocue Analyzer. All-trans-BC levels in uncooked fresh cowpea and amaranth leaves were 806.0 μg/g and 599.0 μg/g dry matter, respectively, while the dehydration and cooking processes retained the β-carotene levels at over 60 %. Consumption of the dehydrated vegetables significantly improved both serum BC and retinol levels (p < 0.05), while the baseline hemoglobin levels improved by 4.6 %. The study has shown that intervention with locally available sun-dried vegetables improves the bioavailability of BC, retinol, and hemoglobin levels among preschool children.

The narrow therapeutic window of glycated hemoglobin and assay variability.

PubMed

Hosseini, S S; Bibler, I; Charles, M A

1999-12-01

Glycated hemoglobin is measured by a variety of assays, each of which has a unique normal level. Our purpose is to show that among the different assays available in the United States, using the same patient's blood sample, assay results may vary widely and may more or less easily achieve a glycated hemoglobin value within the normal range. The following assays were compared using the same patient's blood sample for each pair of assays: glycohemoglobin affinity assay (GHB Reader; Isolab, Akron, OH) versus gel electrophoresis assay (n = 76); Isolab versus ion capture assay (IMX; Abbott Laboratories, Irving, TX) (n = 57); monoclonal antibody assay (DCA2000; Bayer Diagnostics, Pittsburgh, PA) versus IMX (n = 100); and high-performance liquid chromatography (HPLC) assay (Bio-Rad Variant A1c; Bio-Rad Laboratories, Richmond, CA) versus IMX assay (n = 55). Our analyses indicate that a relative ranking can be established for the ease of achieving a normal glycated hemoglobin level. The ranking indicates that the most stringent or difficult assays for achieving a normal level are the Isolab and DCA2000 assays. The intermediate assays are the IMX and Bio-Rad Variant, and the easiest method for achieving a normal value is the gel electrophoresis assay. Our results indicate that various glycated hemoglobin assays vary widely and are associated with more or less difficulty for an individual patient to achieve a glycated hemoglobin level within the normal range. These results are especially significant with respect to (1) the clinically narrow therapeutic window of glycated hemoglobin values in type 1 diabetes to avoid rapidly advancing severe hypoglycemia rates and chronic microvascular complication rates, and (2) the glycated hemoglobin threshold for rapidly advancing macrovascular disease in both type 1 and type 2 patients.

Effectiveness of disease-management programs for improving diabetes care: a meta-analysis.

PubMed

Pimouguet, Clément; Le Goff, Mélanie; Thiébaut, Rodolphe; Dartigues, Jean François; Helmer, Catherine

2011-02-08

We conducted a meta-analysis of randomized controlled trials to assess the effectiveness of disease-management programs for improving glycemic control in adults with diabetes mellitus and to study which components of programs are associated with their effectiveness. We searched several databases for studies published up to December 2009. We included randomized controlled trials involving adults with type 1 or 2 diabetes that evaluated the effect of disease-management programs on glycated hemoglobin (hemoglobin A₁(C)) concentrations. We performed a meta-regression analysis to determine the effective components of the programs. We included 41 randomized controlled trials in our review. Across these trials, disease-management programs resulted in a significant reduction in hemoglobin A₁(C) levels (pooled standardized mean difference between intervention and control groups -0.38 [95% confidence interval -0.47 to -0.29], which corresponds to an absolute mean difference of 0.51%). The finding was robust in the sensitivity analyses based on quality assessment. Programs in which the disease manager was able to start or modify treatment with or without prior approval from the primary care physician resulted in a greater improvement in hemoglobin A₁(C) levels (standardized mean difference -0.60 v. -0.28 in trials with no approval to do so; p < 0.001). Programs with a moderate or high frequency of contact reported a significant reduction in hemoglobin A₁(C) levels compared with usual care; nevertheless, only programs with a high frequency of contact led to a significantly greater reduction compared with low-frequency contact programs (standardized mean difference -0.56 v. -0.30, p = 0.03). Disease-management programs had a clinically moderate but significant impact on hemoglobin A₁(C) levels among adults with diabetes. Effective components of programs were a high frequency of patient contact and the ability for disease managers to adjust treatment with or without prior physician approval.

Effectiveness of disease-management programs for improving diabetes care: a meta-analysis

PubMed Central

Pimouguet, Clément; Le Goff, Mélanie; Thiébaut, Rodolphe; Dartigues, Jean François; Helmer, Catherine

2011-01-01

Background We conducted a meta-analysis of randomized controlled trials to assess the effectiveness of disease-management programs for improving glycemic control in adults with diabetes mellitus and to study which components of programs are associated with their effectiveness. Methods We searched several databases for studies published up to December 2009. We included randomized controlled trials involving adults with type 1 or 2 diabetes that evaluated the effect of disease-management programs on glycated hemoglobin (hemoglobin A1C) concentrations. We performed a meta-regression analysis to determine the effective components of the programs. Results We included 41 randomized controlled trials in our review. Across these trials, disease-management programs resulted in a significant reduction in hemoglobin A1C levels (pooled standardized mean difference between intervention and control groups −0.38 [95% confidence interval −0.47 to −0.29], which corresponds to an absolute mean difference of 0.51%). The finding was robust in the sensitivity analyses based on quality assessment. Programs in which the disease manager was able to start or modify treatment with or without prior approval from the primary care physician resulted in a greater improvement in hemoglobin A1C levels (standardized mean difference −0.60 v. −0.28 in trials with no approval to do so; p < 0.001). Programs with a moderate or high frequency of contact reported a significant reduction in hemoglobin A1C levels compared with usual care; nevertheless, only programs with a high frequency of contact led to a significantly greater reduction compared with low-frequency contact programs (standardized mean difference −0.56 v. −0.30, p = 0.03). Interpretation Disease-management programs had a clinically moderate but significant impact on hemoglobin A1C levels among adults with diabetes. Effective components of programs were a high frequency of patient contact and the ability for disease managers to adjust treatment with or without prior physician approval. PMID:21149524

IV. HEMOGLOBIN INJECTIONS AND CONSERVATION OF PIGMENT BY KIDNEY, LIVER AND SPLEEN

PubMed Central

Newman, William V.; Whipple, George H.

1932-01-01

When the minimal renal threshold for blood hemoglobin is exceeded there is observed a deposit of iron staining pigment in the epithelium of the renal convoluted tubules. At a certain point this epithelium cannot take up more hemoglobin and this coincides with the minimal renal threshold level. When the injections of blood hemoglobin are kept below the minimal renal threshold level we note a complete absence of iron staining pigment in the renal tubular epithelium. Given a deposit of iron staining pigment in the tubular epithelium, it will slowly disappear during rest periods with no hemoglobin injections. Anemia due to bleeding will accelerate this removal of pigment from the renal epithelium and this indicates a conservation of material by the kidney for use in construction of new hemoglobin. Pigment giving a positive stain for iron will be found in the liver and spleen when hemoglobin injections are given, regardless of the renal threshold. Removal of this pigment is accelerated by anemia due to bleeding and as a rule an anemia period of 2 months at a level of 1/3 normal (40 to 50 per cent hemoglobin) will render the spleen, liver and kidney free from iron staining pigment. Pigment giving a positive iron stain is frequently observed in the mesenteric and lower retroperitoneal lymph glands. This is merely a drainage of pigment and phagocytes including pigment from some organ in which the pigment deposit was primary. In stock dogs in this laboratory the hemoglobin level is quite high when the animals are in a perfectly normal state. The blood hemoglobin averages 120 to 150 per cent hemoglobin. In such dogs iron staining pigment in the spleen is a common finding and on occasion is observed in the liver. To establish an accurate base line for the study of iron and iron staining pigment storage due to diet intake one must submit these dogs to a preliminary anemia period of at least 2 months. Muscle hemoglobin has a very low renal threshold and escapes freely into the urine when given intravenously. Contrasting with blood hemoglobin this musde hemoglobin under identical conditions does not cause the deposit of iron staining pigment within the epithelium of the renal tubules. A pigment giving no iron staining reaction may be found in the epithelium of the convoluted tubules of the kidney. Whether this is due to dietary or other factors is uncertain but this indicates pigment conservation by the kidney. Finally we would emphasize again the fact that the kidney is of considerable importance in the conservation of hemoglobin and hemoglobin split products which presumably are utilized to build up new hemoglobin. PMID:19870019

Association in Long-Evans hooded rats of red cell 2,3-diphosphoglycerate levels with hemoglobin types.

PubMed

Brewer, G; Gilman, J; Noble, N; Crews, V

1978-08-01

Two sublines of commercially available Long-Evans hooded rats have been developed by genetic selection. These sublines have widely differing levels of erythrocyte 2,3-diphosphoglycerate (DPG) due to different alleles at a single genetic locus. In the present work, it is shown that rats from the commercial population are also polymorphic at a hemoglobin locus, probably involving two alleles of the IIIbeta-globin chain locus. Particular hemoglobin types have been found to be strongly associated with certain DPG types, not only in the high-DPG and low-DPG lines but also in the commercial population. Two explanations for this association are considered. One is a single-locus hypothesis, with hemoglobin allelic variation causing DPG variation, and the other is a two-locus hypothesis, with marked linkage disequilibrium.

Genetic variants associated with fetal hemoglobin levels show the diverse ethnic origin in Colombian patients with sickle cell anemia.

PubMed

Fong, Cristian; Menzel, Stephan; Lizarralde, María Alejandra; Barreto, Guillermo

2015-01-01

Fetal hemoglobin is an important factor in modulating the severity of sickle cell anemia. Its level in peripheral blood underlies strong genetic determination. Associated loci with increased levels of fetal hemoglobin display population-specific allele frequencies. We investigated the presence and effect of known common genetic variants promoting fetal hemoglobin persistence (rs11886868, rs9399137, rs4895441, and rs7482144) in 60 Colombian patients with sickle cell anemia. Four single nucleotide polymorphisms (SNP) were genotyped by restriction fragment length polymorphisms (RFLP) and the use of the TaqMan procedure. Fetal hemoglobin (HbF) from these patients was quantified using the oxyhemoglobin alkaline denaturation technique. Genotype frequencies were compared with frequencies reported in global reference populations. We detected genetic variants in the four SNPs, reported to be associated with higher HbF levels for all four SNPs in the Colombian patients. Genetic association between SNPs and HbF levels did not reach statistical significance. The frequency of these variants reflected the specific ethnic make-up of our patient population: A high prevalence of rs7482144-'A' reflects the West-African origin of the sickle cell mutation, while high frequencies of rs4895441-'G' and rs11886868-'C' point to a significant influence of an Amerindian ethnic background in the Colombian sickle cell disease population. These results showed that in the sickle cell disease population in Colombia there is not a unique genetic background, but two (African and Amerindian). This unique genetic situation will provide opportunities for a further study of these loci, such as fine-mapping and molecular-biological investigation. Colombian patients are expected to yield a distinctive insight into the effect of modifier loci in sickle cell disease.

[Levels of anemia and hemoglobin in pregnant adolescents who attended health care facilities of Ministry of Health of Peru, 2009-2012].

PubMed

Munares-García, Oscar; Gómez-Guizado, Guillermo

2014-01-01

To determine hemoglobin levels and anemia in pregnant adolescents who attended the health care facilities of the Ministry of Health of Peru between the years 2009 and 2012. Cross-sectional study of secondary data analysis using the Information System of the Nutritional Status of Children and Pregnant Women (SIEN). 265,788 records of pregnant women aged 10 to 19 years were reviewed. Hemoglobin levels (g/dL) and the percentage of anemia in the first, second and third trimesters were measured. Descriptive statistics with confidence intervals at 95% were applied. 3.4% of pregnant women were aged 10 to 14 years (early adolescence), 21.6% between 15 to 16 years (middle adolescence) and 75% between 17 to 19 years (late adolescence). Hemoglobin levels in pregnant adolescents were 11.6 ± 1.3 g/dL in 2009 and 11.5 ± 1.3 g/dL during the years 2010, 2011 and 2012. The overall incidence of anemia for 2009 was 25.1% (95% CI 24.4-25.8); for 2010 was 26.0% (95% CI 25.3-26.6) for 2011 was 26.4% (95% CI 25.8-27.1) and 25.2% for 2012 (95% CI 24.6-25.9). Hemoglobin levels were on average lower for pregnant residents in high Andean areas. About a quarter of pregnant adolescents in our sample had anemia.

IR Spectra of Different O2-Content Hemoglobin from Computational Study: Promising Detector of Hemoglobin Variant in Medical Diagnosis.

PubMed

Zhou, Su-Qin; Chen, Tu-Nan; Ji, Guang-Fu; Wang, En-Ren

2017-06-01

IR spectra of heme and different O 2 -content hemoglobin were studied by the quantum computation method at the molecule level. IR spectra of heme and different O 2 -content hemoglobin were quantificationally characterized from 0 to 100 THz. The IR spectra of oxy-heme and de-oxy-heme are obviously different at the frequency regions of 9.08-9.48, 38.38-39.78, 50.46-50.82, and 89.04-91.00 THz. At 24.72 THz, there exists the absorption peak for oxy-heme, whereas there is not the absorption peak for de-oxy-heme. Whether the heme contains Fe-O-O bond or not has the great influence on its IR spectra and vibration intensities of functional groups in the mid-infrared area. The IR adsorption peak shape changes hardly for different O 2 -content hemoglobin. However, there exist three frequency regions corresponding to the large change of IR adsorption intensities for containing-O 2 hemoglobin in comparison with de-oxy-hemoglobin, which are 11.08-15.93, 44.70-50.22, and 88.00-96.68 THz regions, respectively. The most differential values with IR intensity of different O 2 -content hemoglobin all exceed 1.0 × 10 4  L mol -1  cm -1 . With the increase of oxygen content, the absorption peak appears in the high-frequency region for the containing-O 2 hemoglobin in comparison with de-oxy-hemoglobin. The more the O 2 -content is, the greater the absorption peak is at the high-frequency region. The IR spectra of different O 2 -content hemoglobin are so obviously different in the mid-infrared region that it is very easy to distinguish the hemoglobin variant by means of IR spectra detector. IR spectra of hemoglobin from quantum computation can provide scientific basis and specific identification of hemoglobin variant resulting from different O 2 contents in medical diagnosis.

Mapping of hemoglobin in erythrocytes and erythrocyte ghosts using two photon excitation fluorescence microscopy

NASA Astrophysics Data System (ADS)

Bukara, Katarina; Jovanić, Svetlana; Drvenica, Ivana T.; Stančić, Ana; Ilić, Vesna; Rabasović, Mihailo D.; Pantelić, Dejan; Jelenković, Branislav; Bugarski, Branko; Krmpot, Aleksandar J.

2017-02-01

The present study describes utilization of two photon excitation fluorescence (2PE) microscopy for visualization of the hemoglobin in human and porcine erythrocytes and their empty membranes (i.e., ghosts). High-quality, label- and fixation-free visualization of hemoglobin was achieved at excitation wavelength 730 nm by detecting visible autofluorescence. Localization in the suspension and spatial distribution (i.e., mapping) of residual hemoglobin in erythrocyte ghosts has been resolved by 2PE. Prior to the 2PE mapping, the presence of residual hemoglobin in the bulk suspension of erythrocyte ghosts was confirmed by cyanmethemoglobin assay. 2PE analysis revealed that the distribution of hemoglobin in intact erythrocytes follows the cells' shape. Two types of erythrocytes, human and porcine, characterized with discocyte and echinocyte morphology, respectively, showed significant differences in hemoglobin distribution. The 2PE images have revealed that despite an extensive washing out procedure after gradual hypotonic hemolysis, a certain amount of hemoglobin localized on the intracellular side always remains bound to the membrane and cannot be eliminated. The obtained results open the possibility to use 2PE microscopy to examine hemoglobin distribution in erythrocytes and estimate the purity level of erythrocyte ghosts in biotechnological processes.

Assessment of Microcirculatory Hemoglobin Levels in Normal and Diabetic Subjects using Diffuse Reflectance Spectroscopy in the Visible Region — a Pilot Study

NASA Astrophysics Data System (ADS)

Sujatha, N.; Anand, B. S. Suresh; Nivetha, K. Bala; Narayanamurthy, V. B.; Seshadri, V.; Poddar, R.

2015-07-01

Light-based diagnostic techniques provide a minimally invasive way for selective biomarker estimation when tissues transform from a normal to a malignant state. Spectroscopic techniques based on diffuse reflectance characterize the changes in tissue hemoglobin/oxygenation levels during the tissue transformation process. Recent clinical investigations have shown that changes in tissue oxygenation and microcirculation are observed in diabetic subjects in the initial and progressive stages. In this pilot study, we discuss the potential of diffuse reflectance spectroscopy (DRS) in the visible (Vis) range to differentiate the skin microcirculatory hemoglobin levels between normal and advanced diabetic subjects with and without neuropathy. Average concentration of hemoglobin as well as hemoglobin oxygen saturation within the probed tissue volume is estimated for a total of four different sites in the foot sole. The results indicate a statistically significant decrease in average total hemoglobin and increase in hemoglobin oxygen saturation levels for diabetic foot compared with a normal foot. The present study demonstrates the ability of reflectance spectroscopy in the Vis range to determine and differentiate the changes in tissue hemoglobin and hemoglobin oxygen saturation levels in normal and diabetic subjects.

Efficacy and safety of the Gardos channel blocker, senicapoc (ICA-17043), in patients with sickle cell anemia.

PubMed

Ataga, Kenneth I; Smith, Wally R; De Castro, Laura M; Swerdlow, Paul; Saunthararajah, Yogen; Castro, Oswaldo; Vichinsky, Elliot; Kutlar, Abdullah; Orringer, Eugene P; Rigdon, Greg C; Stocker, Jonathan W

2008-04-15

Senicapoc, a novel Gardos channel inhibitor, limits solute and water loss, thereby preserving sickle red blood cell (RBC) hydration. Because hemoglobin S polymerization is profoundly influenced by intracellular hemoglobin concentration, senicapoc could improve sickle RBC survival. In a 12-week, multicenter, phase 2, randomized, double-blind, dose-finding study, we evaluated senicapoc's safety and its effect on hemoglobin level and markers of RBC hemolysis in sickle cell anemia patients. The patients were randomized into 3 treatment arms: placebo; low-dose (6 mg/day) senicapoc; and high-dose (10 mg/day) senicapoc. For the primary efficacy end point (change in hemoglobin level from baseline), the mean response to high-dose senicapoc treatment exceeded placebo (6.8 g/L [0.68 g/dL] vs 0.1 g/L [0.01 g/dL], P < .001). Treatment with high-dose senicapoc also produced significant decreases in such secondary end points as percentage of dense RBCs (-2.41 vs -0.08, P < .001); reticulocytes (-4.12 vs -0.46, P < .001); lactate dehydrogenase (-121 U/L vs -15 U/L, P = .002); and indirect bilirubin (-1.18 mg/dL vs 0.12 mg/dL, P < .001). Finally, senicapoc was safe and well tolerated. The increased hemoglobin concentration and concomitant decrease in the total number of reticulocytes and various markers of RBC destruction following senicapoc administration suggests a possible increase in the survival of sickle RBCs. This study is registered at http://clinicaltrials.gov as NCT00040677.

The Genetic Architecture of Adaptations to High Altitude in Ethiopia

PubMed Central

Alkorta-Aranburu, Gorka; Beall, Cynthia M.; Witonsky, David B.; Gebremedhin, Amha; Pritchard, Jonathan K.; Di Rienzo, Anna

2012-01-01

Although hypoxia is a major stress on physiological processes, several human populations have survived for millennia at high altitudes, suggesting that they have adapted to hypoxic conditions. This hypothesis was recently corroborated by studies of Tibetan highlanders, which showed that polymorphisms in candidate genes show signatures of natural selection as well as well-replicated association signals for variation in hemoglobin levels. We extended genomic analysis to two Ethiopian ethnic groups: Amhara and Oromo. For each ethnic group, we sampled low and high altitude residents, thus allowing genetic and phenotypic comparisons across altitudes and across ethnic groups. Genome-wide SNP genotype data were collected in these samples by using Illumina arrays. We find that variants associated with hemoglobin variation among Tibetans or other variants at the same loci do not influence the trait in Ethiopians. However, in the Amhara, SNP rs10803083 is associated with hemoglobin levels at genome-wide levels of significance. No significant genotype association was observed for oxygen saturation levels in either ethnic group. Approaches based on allele frequency divergence did not detect outliers in candidate hypoxia genes, but the most differentiated variants between high- and lowlanders have a clear role in pathogen defense. Interestingly, a significant excess of allele frequency divergence was consistently detected for genes involved in cell cycle control and DNA damage and repair, thus pointing to new pathways for high altitude adaptations. Finally, a comparison of CpG methylation levels between high- and lowlanders found several significant signals at individual genes in the Oromo. PMID:23236293

Hemoglobin Test: MedlinePlus Lab Test Information

MedlinePlus

... 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 ...

Erythropoietin, Iron Depletion and Relative Thrombocytosis: A Possible Explanation for Hemoglobin-Survival Paradox in Chronic Kidney Disease

PubMed Central

Streja, Elani; Kovesdy, Csaba P; Greenland, Sander; Kopple, Joel D.; McAllister, Charles J; Nissenson, Allen R; Kalantar-Zadeh, Kamyar

2017-01-01

Background High doses of human recombinant erythropoietin (rHuEPO) to achieve hemoglobin levels above 13 g/dL in chronic kidney disease appear associated with elevated mortality. Study Design We conducted logistic regression and survival analyses in a retrospective cohort of maintenance hemodialysis (MHD) patients to examine the hypothesis that the induced iron depletion with resultant relative thrombocytosis may be a possible contributor to the link between the high rHuEPO dose associated hemoglobin ≥13 g/dL and mortality. Setting & Participants The national database of a large dialysis organization (DaVita) with 40,787 MHD patients during July to December 2001 and their survival up to July 2004 were examined. Predictors Hemoglobin level, platelet count and administered rHuEPO dose during each calendar quarter. Outcomes & other Measurements Case-mix adjusted 3-year all-cause mortality; and measures of iron stores including serum ferritin and iron saturation ratio (ISAT). Results Higher platelet count was associated with lower iron stores and higher prescribed rHuEPO dose. Compared to hemoglobin of 12-13 g/dL, hemoglobin ≥13 g/dL was associated with increased mortality in the presence of relative thrombocytosis, i.e., platelet count ≥300,000/μl, (case-mix adjusted death-rate ratio [RR]: 1.21, 95% confidence limits [CL]: 1.02–1.44, P=0.03) as opposed to the absence of relative thrombocytosis (RR: 1.04, 95% CL: 0.98–1.08, P=0.13). Prescribed rHuEPO dose >20,000 units/week was associated with higher likelihood of iron depletion (ISAT<20%) and relative thrombocytosis (case-mix adjusted odds ratio: 2.53 [CL: 2.37–2.69] and 1.36 [CL: 1.30–1.42], respectively, p<0.001) and increased mortality over 3 years (death-rate ratio of 1.59, CL: 1.54, 1.65, p<0.001). Limitations Our results may incorporate uncontrolled confounding. Achieved hemoglobin may have different mortality-predictability than targeted hemoglobin. Conclusions Iron depletion and associated relative thrombocytosis might contribute to increased mortality when administering high rHuEPO doses to achieve hemoglobin ≥13 g/dL in MHD patients. Randomized trials are needed to test these observational associations. PMID:18760517

Identification of Hemoglobin Levels Based on Anthropometric Indices in Elderly Koreans

PubMed Central

Kim, Jong Yeol

2016-01-01

Objectives Anemia is independently and strongly associated with an increased risk of mortality in older people and is also strongly associated with obesity. The objectives of the present study were to examine the associations between the hemoglobin level and various anthropometric indices, to predict low and normal hemoglobin levels using combined anthropometric indices, and to assess differences in the hemoglobin level and anthropometric indices between Korean men and women. Methods A total of 7,156 individuals ranging in age from 53–90 years participated in this retrospective cross-sectional study. Binary logistic regression (LR) and naïve Bayes (NB) models were used to identify significant differences in the anthropometric indices between subjects with low and normal hemoglobin levels and to assess the predictive power of these indices for the hemoglobin level. Results Among all of the variables, age displayed the strongest association with the hemoglobin level in both men (p < 0.0001, odds ratio [OR] = 0.487, area under the receiver operating characteristic curve based on the LR [LR-AUC] = 0.702, NB-AUC = 0.701) and women (p < 0.0001, OR = 0.636, LR-AUC = 0.625, NB-AUC = 0.624). Among the anthropometric indices, weight and body mass index (BMI) were the best predictors of the hemoglobin level. The predictive powers of all of the variables were higher in men than in women. The AUC values for the NB-Wrapper and LR-Wrapper predictive models generated using combined anthropometric indices were 0.734 and 0.723, respectively, for men and 0.649 and 0.652, respectively, for women. The use of combined anthropometric indices may improve the predictive power for the hemoglobin level. Discussion Among the various anthropometric indices, with the exception of age, we did not identify any indices that were better predictors than weight and BMI for low and normal hemoglobin levels. In addition, none of the ratios between pairs of indices were good indicators of the hemoglobin level. Finally, the Korean men tended to have higher associations between the anthropometric indices and anemia than the women. PMID:27812118

Hemoglobin diffusion and the dynamics of oxygen capture by red blood cells.

PubMed

Longeville, Stéphane; Stingaciu, Laura-Roxana

2017-09-05

Translational diffusion of macromolecules in cell is generally assumed to be anomalous due high macromolecular crowding of the milieu. Red blood cells are a special case of cells filled quasi exclusively (95% of the dry weight of the cell) with an almost spherical protein: hemoglobin. Hemoglobin diffusion has since a long time been recognized as facilitating the rate of oxygen diffusion through a solution. We address in this paper the question on how hemoglobin diffusion in the red blood cells can help the oxygen capture at the cell level and hence to improve oxygen transport. We report a measurement by neutron spin echo spectroscopy of the diffusion of hemoglobin in solutions with increasing protein concentration. We show that hemoglobin diffusion in solution can be described as Brownian motion up to physiological concentration and that hemoglobin diffusion in the red blood cells and in solutions at similar concentration are the same. Finally, using a simple model and the concentration dependence of the diffusion of the protein reported here, we show that hemoglobin concentration observed in human red blood cells ([Formula: see text]330 g.L -1 ) corresponds to an optimum for oxygen transport for individuals under strong activity.

Hemoglobin diffusion and the dynamics of oxygen capture by red blood cells

DOE PAGES

Longeville, Stéphane; Stingaciu, Laura-Roxana

2017-09-05

Translational diffusion of macromolecules in cell is generally assumed to be anomalous due high macromolecular crowding of the milieu. Red blood cells are a special case of cells filled quasi exclusively (95% of the dry weight of the cell) with an almost spherical protein: hemoglobin. Hemoglobin diffusion has since a long time been recognized as facilitating the rate of oxygen diffusion through a solution. We address in this paper the question on how hemoglobin diffusion in the red blood cells can help the oxygen capture at the cell level and hence to improve oxygen transport. We report a measurement bymore » neutron spin echo spectroscopy of the diffusion of hemoglobin in solutions with increasing protein concentration. We show that hemoglobin diffusion in solution can be described as Brownian motion up to physiological concentration and that hemoglobin diffusion in the red blood cells and in solutions at similar concentration are the same. Finally, using a simple model and the concentration dependence of the diffusion of the protein reported here, we show that hemoglobin concentration observed in human red blood cells (≃330 g.L -1) corresponds to an optimum for oxygen transport for individuals under strong activity.« less

Hemoglobin diffusion and the dynamics of oxygen capture by red blood cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Longeville, Stéphane; Stingaciu, Laura-Roxana

Translational diffusion of macromolecules in cell is generally assumed to be anomalous due high macromolecular crowding of the milieu. Red blood cells are a special case of cells filled quasi exclusively (95% of the dry weight of the cell) with an almost spherical protein: hemoglobin. Hemoglobin diffusion has since a long time been recognized as facilitating the rate of oxygen diffusion through a solution. We address in this paper the question on how hemoglobin diffusion in the red blood cells can help the oxygen capture at the cell level and hence to improve oxygen transport. We report a measurement bymore » neutron spin echo spectroscopy of the diffusion of hemoglobin in solutions with increasing protein concentration. We show that hemoglobin diffusion in solution can be described as Brownian motion up to physiological concentration and that hemoglobin diffusion in the red blood cells and in solutions at similar concentration are the same. Finally, using a simple model and the concentration dependence of the diffusion of the protein reported here, we show that hemoglobin concentration observed in human red blood cells (≃330 g.L -1) corresponds to an optimum for oxygen transport for individuals under strong activity.« less

[Effect of high-intensity interval training on the reduction of glycosylated hemoglobin in type-2 diabetic adult patients].

PubMed

Aguilera Eguía, Raúl Alberto; Russell Guzmán, Javier Antonio; Soto Muñoz, Marcelo Enrique; Villegas González, Bastián Eduardo; Poblete Aro, Carlos Emilio; Ibacache Palma, Alejandro

2015-03-05

Type 2 diabetes mellitus is one of the major non-communicable chronic diseases in the world. Its prevalence in Chile is significant, and complications associated with this disease involve great costs, which is why prevention and treatment of this condition are essential. Physical exercise is an effective means for prevention and treatment of type 2 diabetes mellitus. The emergence of new forms of physical training, such as "high intensity interval training", presents novel therapeutic alternatives for patients and health care professionals. To assess the validity and applicability of the results regarding the effectiveness of high intensity interval training in reducing glycosylated hemoglobin in adult patients with type 2 diabetes mellitus and answer the following question: In subjects with type 2 diabetes, can the method of high intensity interval training compared to moderate intensity exercise decrease glycosylated hemoglobin? We performed a critical analysis of the article "Feasibility and preliminary effectiveness of high intensity interval training in type 2 diabetes". We found no significant differences in the amount of glycosylated hemoglobin between groups of high intensity interval training and moderate-intensity exercise upon completion of the study (p>0.05). In adult patients with type 2 diabetes mellitus, high intensity interval training does not significantly improve glycosylated hemoglobin levels. Despite this, the high intensity interval training method shows as much improvement in body composition and physical condition as the moderate intensity exercise program.

Hemoglobin levels and transfusions in neurocritically ill patients: a systematic review of comparative studies

PubMed Central

2012-01-01

Introduction Accumulating evidence suggests that, in critically ill patients, a lower hemoglobin transfusion threshold is safe. However, the optimal hemoglobin level and associated transfusion threshold remain unknown in neurocritically ill patients. Methods We conducted a systematic review of comparative studies (randomized and nonrandomized) to evaluate the effect of hemoglobin levels on mortality, neurologic function, intensive care unit (ICU) and hospital length of stay, duration of mechanical ventilation, and multiple organ failure in adult and pediatric neurocritically ill patients. We searched MEDLINE, The Cochrane Central Register of Controlled Trials, Embase, Web of Knowledge, and Google Scholar. Studies focusing on any neurocritical care conditions were included. Data are presented by using odds ratios for dichotomous outcomes and mean differences for continuous outcomes. Results Among 4,310 retrieved records, six studies met inclusion criteria (n = 537). Four studies were conducted in traumatic brain injury (TBI), one in subarachnoid hemorrhage (SAH), and one in a mixed population of neurocritically ill patients. The minimal hemoglobin levels or transfusion thresholds ranged from 7 to 10 g/dl in the lower-Hb groups and from 9.3 to 11.5 g/dl in the higher-Hb groups. Three studies had a low risk of bias, and three had a high risk of bias. No effect was observed on mortality, duration of mechanical ventilation, or multiple organ failure. In studies reporting on length of stay (n = 4), one reported a significant shorter ICU stay (mean, -11.4 days (95% confidence interval, -16.1 to -6.7)), and one, a shorter hospital stay (mean, -5.7 days (-10.3 to -1.1)) in the lower-Hb groups, whereas the other two found no significant association. Conclusions We found insufficient evidence to confirm or refute a difference in effect between lower- and higher-Hb groups in neurocritically ill patients. Considering the lack of evidence regarding long-term neurologic functional outcomes and the high risk of bias of half the studies, no recommendation can be made regarding which hemoglobin level to target and which associated transfusion strategy (restrictive or liberal) to favor in neurocritically ill patients. PMID:22471943

Hepcidin level predicts hemoglobin concentration in individuals undergoing repeated phlebotomy.

PubMed

Mast, Alan E; Schlumpf, Karen S; Wright, David J; Johnson, Bryce; Glynn, Simone A; Busch, Michael P; Olbina, Gordana; Westerman, Mark; Nemeth, Elizabeta; Ganz, Tomas

2013-08-01

Dietary iron absorption is regulated by hepcidin, an iron regulatory protein produced by the liver. Hepcidin production is regulated by iron stores, erythropoiesis and inflammation, but its physiology when repeated blood loss occurs has not been characterized. Hepcidin was assayed in plasma samples obtained from 114 first-time/reactivated (no blood donations in preceding 2 years) female donors and 34 frequent (≥3 red blood cell donations in preceding 12 months) male donors as they were phlebotomized ≥4 times over 18-24 months. Hepcidin levels were compared to ferritin and hemoglobin levels using multivariable repeated measures regression models. Hepcidin, ferritin and hemoglobin levels declined with increasing frequency of donation in the first-time/reactivated females. Hepcidin and ferritin levels correlated well with each other (Spearman's correlation of 0.74), but on average hepcidin varied more between donations for a given donor relative to ferritin. In a multivariable repeated measures regression model the predicted inter-donation decline in hemoglobin varied as a function of hepcidin and ferritin; hemoglobin was 0.51 g/dL lower for subjects with low (>45.7 ng/mL) or decreasing hepcidin and low ferritin (>26 ng/mL), and was essentially zero for other subjects including those with high (>45.7 ng/mL) or increasing hepcidin and low ferritin (>26 ng/mL) levels (P<0.001). In conclusion, hepcidin levels change rapidly in response to dietary iron needed for erythropoiesis. The dynamic regulation of hepcidin in the presence of a low levels of ferritin suggests that plasma hepcidin concentration may provide clinically useful information about an individual's iron status (and hence capacity to tolerate repeated blood donations) beyond that of ferritin alone. Clinicaltrials.gov identifier: NCT00097006.

Immune hemolytic anemia

MedlinePlus

... Absolute reticulocyte count Direct or indirect Coombs test Hemoglobin in the urine LDH (level of this enzyme ... of tissue damage) Red blood cell count (RBC), hemoglobin, and hematocrit Serum bilirubin level Serum free hemoglobin ...

2,4,6-Trinitrotoluene (TNT) air concentrations, hemoglobin changes, and anemia cases in respirator protected TNT munitions demilitarization workers.

PubMed

Bradley, Melville D

2011-03-01

2,4,6-Trinitrotoluene (TNT) is an explosive used in munitions production that is known to cause both aplastic and hemolytic anemia in exposed workers. Anemia in a TNT worker is considered a sentinel health event (occupational) (SHE(O)) in the United States (US). Deaths have been reported secondary to aplastic anemia. Studies have shown that TNT systemic absorption is significant by both the respiratory and dermal routes. No studies encountered looked at hemoglobin change or anemia cases in respiratory protected workers. It is hypothesized that respiratory protection is insufficient to protect TNT workers from the risk of anemia development and hemoglobin concentration drop. A records review of eight groups of respiratory protected TNT workers' pre-exposure hemoglobin levels were compared with their during-exposure hemoglobin levels for statistically significant (alpha level 0.05) hemoglobin level changes, and anemia cases were recorded. A curve estimation analysis was performed between mean TNT air concentrations and mean hemoglobin change values. Statistically significant hemoglobin level drops and anemia cases were apparent at TNT air concentrations about the REL and PEL in respiratory protected workers. There were no anemia cases or statistically significant hemoglobin level drops at concentrations about the TLV, however. A statistically significant inverse non-linear regression model was found to be the best fit for regressing hemoglobin change on TNT air concentration. Respiratory protection may be inadequate to prevent workers who are at risk for TNT skin absorption from developing anemia. This study contributes evidence that the TLV should be considered for adoption as the new PEL.

Relationship of hemoglobin to occupational exposure to motor vehicle exhaust.

PubMed

Potula, V; Hu, H

1996-01-01

To study the relationship of hemoglobin to exposure to motor vehicle exhaust. Survey. Traffic police, bus drivers, and auto-shop workers (all exposed to auto exhaust in Madras, India) and unexposed office workers. We measured levels of blood lead (by graphite furnace atomic absorption spectrophotometry), and hemoglobin. Information also was collected on age, employment duration, smoking status, alcohol ingestion, and diet type (vegetarian or nonvegetarian). Increasing exposure to motor vehicle exhaust, as reflected by job category, was significantly associated with lower levels of hemoglobin (p < 0.01). A final multivariate regression model was constructed that began with indicator variables for each job (with office workers as the reference category) and included age, duration of employment, blood lead level, alcohol ingestion, dietary type, and smoking status. After a backward-elimination procedure, employment duration as an auto-shop worker or bus driver remained as significant correlates of lower hemoglobin level and current smoking and long employment duration as significant correlates of higher hemoglobin level. Occupational exposure to automobile exhaust may be a risk factor for decreased hemoglobin level in Madras. This effect appears to be independent of blood lead level and may represent hematopoietic suppression incurred by benzene or accumulated lead burden (which is not well reflected by blood lead levels). Smoking probably increased hemoglobin level through the chronic effects of exposure to carbon monoxide. In this study, a long employment duration may have served as a proxy for better socioeconomic, and therefore, better nutritional status.

A review of variant hemoglobins interfering with hemoglobin A1c measurement.

PubMed

Little, Randie R; Roberts, William L

2009-05-01

Hemoglobin A1c (HbA1c) is used routinely to monitor long-term glycemic control in people with diabetes mellitus, as HbA1c is related directly to risks for diabetic complications. The accuracy of HbA1c methods can be affected adversely by the presence of hemoglobin (Hb) variants or elevated levels of fetal hemoglobin (HbF). The effect of each variant or elevated HbF must be examined with each specific method. The most common Hb variants worldwide are HbS, HbE, HbC, and HbD. All of these Hb variants have single amino acid substitutions in the Hb beta chain. HbF is the major hemoglobin during intrauterine life; by the end of the first year, HbF falls to values close to adult levels of approximately 1%. However, elevated HbF levels can occur in certain pathologic conditions or with hereditary persistence of fetal hemoglobin. In a series of publications over the past several years, the effects of these four most common Hb variants and elevated HbF have been described. There are clinically significant interferences with some methods for each of these variants. A summary is given showing which methods are affected by the presence of the heterozygous variants S, E, C, and D and elevated HbF. Methods are divided by type (immunoassay, ion-exchange high-performance liquid chromatography, boronate affinity, other) with an indication of whether the result is artificially increased or decreased by the presence of a Hb variant. Laboratorians should be aware of the limitations of their method with respect to these interferences. 2009 Diabetes Technology Society.

[Hemoglobin and testosterone: importance on high altitude acclimatization and adaptation].

PubMed

Gonzales, Gustavo F

2011-03-01

The different types of response mechanisms that the organism uses when exposed to hypoxia include accommodation, acclimatization and adaptation. Accommodation is the initial response to acute exposure to high altitude hypoxia and is characterized by an increase in ventilation and heart rate. Acclimatization is observed in individuals temporarily exposed to high altitude, and to some extent, it enables them to tolerate the high altitudes. In this phase, erythropoiesis is increased, resulting in higher hemoglobin and hematocrit levels to improve oxygen delivery capacity. Adaptation is the process of natural acclimatization where genetical variations and acclimatization play a role in allowing subjects to live without any difficulties at high altitudes. Testosterone is a hormone that regulates erythropoiesis and ventilation and could be associated to the processes of acclimatization and adaptation to high altitude. Excessive erythrocytosis, which leads to chronic mountain sickness, is caused by low arterial oxygen saturation, ventilatory inefficiency and reduced ventilatory response to hypoxia. Testosterone increases during acute exposure to high altitude and also in natives at high altitude with excessive erythrocytosis. Results of current research allow us to conclude that increase in serum testosterone and hemoglobin is adequate for acclimatization, as they improve oxygen transport, but not for high altitude adaptation, since high serum testosterone levels are associated to excessive erythrocytosis.

Determinants of anemia among young children in rural India.

PubMed

Pasricha, Sant-Rayn; Black, James; Muthayya, Sumithra; Shet, Anita; Bhat, Vijay; Nagaraj, Savitha; Prashanth, N S; Sudarshan, H; Biggs, Beverley-Ann; Shet, Arun S

2010-07-01

More than 75% of Indian toddlers are anemic. Data on factors associated with anemia in India are limited. The objective of this study was to determine biological, nutritional, and socioeconomic risk factors for anemia in this vulnerable age group. We conducted a cross-sectional study of children aged 12 to 23 months in 2 rural districts of Karnataka, India. Children were excluded if they were unwell or had received a blood transfusion. Hemoglobin, ferritin, folate, vitamin B(12), retinol-binding protein, and C-reactive protein (CRP) levels were determined. Children were also tested for hemoglobinopathy, malaria infection, and hookworm infestation. Anthropometric measurements, nutritional intake, family wealth, and food security were recorded. In addition, maternal hemoglobin level was measured. Anemia (hemoglobin level < 11.0 g/dL) was detected in 75.3% of the 401 children sampled. Anemia was associated with iron deficiency (low ferritin level), maternal anemia, and food insecurity. Children's ferritin levels were directly associated with their iron intake and CRP levels and with maternal hemoglobin level and inversely associated with continued breastfeeding and the child's energy intake. A multivariate model for the child's hemoglobin level revealed associations with log(ferritin level) (coefficient: 1.20; P < .001), folate level (0.05; P < .01), maternal hemoglobin level (0.16; P < .001), family wealth index (0.02; P < .05), child's age (0.05 per month; P < .005), hemoglobinopathy (-1.51; P < .001), CRP level (-0.18; P < .001), and male gender (-0.38; P < .05). Wealth index and food insecurity could be interchanged in this model. Hemoglobin level was primarily associated with iron status in these Indian toddlers; however, maternal hemoglobin level, family wealth, and food insecurity were also important factors. Strategies for minimizing childhood anemia must include optimized iron intake but should simultaneously address maternal anemia, poverty, and food insecurity.

Bioimaging techniques for subcellular localization of plant hemoglobins and measurement of hemoglobin-dependent nitric oxide scavenging in planta.

PubMed

Hebelstrup, Kim H; Østergaard-Jensen, Erik; Hill, Robert D

2008-01-01

Plant hemoglobins are ubiquitous in all plant families. They are expressed at low levels in specific tissues. Several studies have established that plant hemoglobins are scavengers of nitric oxide (NO) and that varying the endogenous level of hemoglobin in plant cells negatively modulates bioactivity of NO generated under hypoxic conditions or during cellular signaling. Earlier methods for determination of hemoglobin-dependent scavenging in planta were based on measuring activity in whole plants or organs. Plant hemoglobins do not contain specific organelle localization signals; however, earlier reports on plant hemoglobin have demonstrated either cytosolic or nuclear localization, depending on the method or cell type investigated. We have developed two bioimaging techniques: one for visualization of hemoglobin-catalyzed scavenging of NO in specific cells and another for visualization of subcellular localization of green fluorescent protein-tagged plant hemoglobins in transformed Arabidopsis thaliana plants.

Biomarker analysis of hemoglobin adducts of acrylamide and glycidamide enantiomers for mid-term internal exposure assessment by isotope dilution ultra-high performance liquid chromatography tandem mass spectrometry.

PubMed

Zhang, Yu; Wang, Qiao; Zhang, Gong; Jia, Wei; Ren, Yiping; Wu, Yongning

2018-02-01

Hemoglobin (Hb) adducts of acrylamide (AA) and its oxidative metabolite glycidamide (GA) are important biomarkers for evaluating the mid-term exposure of acrylamide toxicity in vivo. Taking pentafluoro-2-methylphenyl isothiocyanates of N-(2-carbamoylethyl)valine (AAVal-PFPTH) and N-(2-carbamoyl-2-hydroxyethy)valine (GAVal-PFPTH) as target analytes, we developed an isotope dilution ultra-high performance liquid chromatograph tandem mass spectrometry (UHPLC-MS/MS) method for the simultaneous determination of AA and GA hemoglobin (Hb) adducts under the electroscopy ionization negative (ESI‾) mode in the present work. Among them, the enantiomer pair of GA-Hb adducts was firstly identified and successfully separated at baseline level. The method achieved high sensitivity with the LOD and LOQ ranging 1.43-5.05pmol/g Hb and 4.78-16.82pmol/g Hb, respectively. The recovery rates with low, intermediate and high spiking levels were calculated as 97.0-105.2%, 97.4-106.4% and 100.3-111.2%, respectively. Acceptable within-laboratory reproducibility (RSD < 13.7%) substantially supported the robustness of current UHPLC-MS/MS method, which was successfully applied to measure the hemoglobin adducts of acrylamide and glycidamide enantiomers in blood of both rats and humans. A linear exposure assessment model was developed for estimating the daily exposure to acrylamide in humans via considering acrylamide hemoglobin adducts as variables, indicating a novel connect between biomarker-based internal exposure and dietary-based external exposure. Overall, the present instrumental analysis and related internal exposure assessment model provide a substantially methodological support for profiling the internal biological exposure and estimating the external dietary exposure to acrylamide. Copyright © 2017 Elsevier B.V. All rights reserved.

Genetic Convergence in the Adaptation of Dogs and Humans to the High-Altitude Environment of the Tibetan Plateau

PubMed Central

Wang, Guo-Dong; Fan, Ruo-Xi; Zhai, Weiwei; Liu, Fei; Wang, Lu; Zhong, Li; Wu, Hong; Yang, He-Chuan; Wu, Shi-Fang; Zhu, Chun-Ling; Li, Yan; Gao, Yun; Ge, Ri-Li; Wu, Chung-I; Zhang, Ya-Ping

2014-01-01

The high-altitude hypoxic environment represents one of the most extreme challenges for mammals. Previous studies of humans on the Tibetan plateau and in the Andes Mountains have identified statistical signatures of selection in different sets of loci. Here, we first measured the hemoglobin levels in village dogs from Tibet and those from Chinese lowlands. We found that the hemoglobin levels are very similar between the two groups, suggesting that Tibetan dogs might share similar adaptive strategies as the Tibetan people. Through a whole-genome sequencing approach, we have identified EPAS1 and HBB as candidate genes for the hypoxic adaptation on the Tibetan plateau. The population genetic analysis shows a significant convergence between humans and dogs in Tibet. The similarities in the sets of loci that exhibit putative signatures of selection and the hemoglobin levels between humans and dogs of the same environment, but not between human populations in different regions, suggests an extraordinary landscape of convergent evolution between human beings and their best friend on the Tibetan plateau. PMID:25091388

Candidate Sequence Variants and Fetal Hemoglobin in Children with Sickle Cell Disease Treated with Hydroxyurea

PubMed Central

Green, Nancy S.; Ender, Katherine L.; Pashankar, Farzana; Driscoll, Catherine; Giardina, Patricia J.; Mullen, Craig A.; Clark, Lorraine N.; Manwani, Deepa; Crotty, Jennifer; Kisselev, Sergey; Neville, Kathleen A.; Hoppe, Carolyn; Barral, Sandra

2013-01-01

Background Fetal hemoglobin level is a heritable complex trait that strongly correlates swith the clinical severity of sickle cell disease. Only few genetic loci have been identified as robustly associated with fetal hemoglobin in patients with sickle cell disease, primarily adults. The sole approved pharmacologic therapy for this disease is hydroxyurea, with effects largely attributable to induction of fetal hemoglobin. Methodology/Principal Findings In a multi-site observational analysis of children with sickle cell disease, candidate single nucleotide polymorphisms associated with baseline fetal hemoglobin levels in adult sickle cell disease were examined in children at baseline and induced by hydroxyurea therapy. For baseline levels, single marker analysis demonstrated significant association with BCL11A and the beta and epsilon globin loci (HBB and HBE, respectively), with an additive attributable variance from these loci of 23%. Among a subset of children on hydroxyurea, baseline fetal hemoglobin levels explained 33% of the variance in induced levels. The variant in HBE accounted for an additional 13% of the variance in induced levels, while variants in the HBB and BCL11A loci did not contribute beyond baseline levels. Conclusions/Significance These findings clarify the overlap between baseline and hydroxyurea-induced fetal hemoglobin levels in pediatric disease. Studies assessing influences of specific sequence variants in these and other genetic loci in larger populations and in unusual hydroxyurea responders are needed to further understand the maintenance and therapeutic induction of fetal hemoglobin in pediatric sickle cell disease. PMID:23409025

Longitudinal Discriminant Analysis of Hemoglobin Level for Predicting Preeclampsia

PubMed Central

Nasiri, Malihe; Faghihzadeh, Soghrat; Alavi Majd, Hamid; Zayeri, Farid; Kariman, Noorosadat; Safavi Ardebili, Nastaran

2015-01-01

Background: Preeclampsia is one of the most serious complications during pregnancy with important effects on health of mother and fetus that causes maternal and fetal morbidity and mortality. This study was performed to evaluate whether high levels of hemoglobin may increase the risk of preeclampsia. Objectives: The present study aimed to predict preeclampsia by the hemoglobin profiles through longitudinal discriminant analysis and comparing the error rate of discrimination in longitudinal and cross sectional data. Patients and Methods: In a prospective cohort study from October 2010 to July 2011, 650 pregnant women referred to the prenatal clinic of Milad Hospital in Tehran were evaluated in 3 stages. The hemoglobin level of each woman was measured in the first, second, and third trimester of pregnancy by an expert technician. The subjects were followed up to delivery and preeclampsia was the main outcome under study. The covariance pattern and linear-mixed effects models are common methods that were applied for discriminant analysis of longitudinal data. Also Student t, Mann-Whitney U, and chi-square tests were used for comparing the demographic and clinical characteristics between two groups. Statistical analyses were performed using the SAS software version 9.1. Results: The prevalence rate of preeclampsia was 7.2% (47 women). The women with preeclampsia had a higher mean of hemoglobin values and the difference was 0.46 g/dL (P = 0.003). Also the mean of hemoglobin in the first trimester was higher than that of the second trimester, and was lower than that of the third trimester and the differences were significant (P = 0.015 and P < 0.001, respectively). The sensitivity for longitudinal data and cross-sectional data in three trimesters was 90%, 67%, 72%, and 54% and the specificity was 88%, 55%, 63%, and 50%, respectively. Conclusions: The levels of hemoglobin can be used to predict preeclampsia and monitoring the pregnant women and its regular measure in 3 trimesters help us to identify women at risk for preeclampsia. PMID:26019901

Fetal hemoglobin in sickle cell anemia: The Arab-Indian haplotype and new therapeutic agents.

PubMed

Habara, Alawi H; Shaikho, Elmutaz M; Steinberg, Martin H

2017-11-01

Fetal hemoglobin (HbF) has well-known tempering effects on the symptoms of sickle cell disease and its levels vary among patients with different haplotypes of the sickle hemoglobin gene. Compared with sickle cell anemia haplotypes found in patients of African descent, HbF levels in Saudi and Indian patients with the Arab-Indian (AI) haplotype exceed that in any other haplotype by nearly twofold. Genetic association studies have identified some loci associated with high HbF in the AI haplotype but these observations require functional confirmation. Saudi patients with the Benin haplotype have HbF levels almost twice as high as African patients with this haplotype but this difference is unexplained. Hydroxyurea is still the only FDA approved drug for HbF induction in sickle cell disease. While most patients treated with hydroxyurea have an increase in HbF and some clinical improvement, 10 to 20% of adults show little response to this agent. We review the genetic basis of HbF regulation focusing on sickle cell anemia in Saudi Arabia and discuss new drugs that can induce increased levels of HbF. © 2017 Wiley Periodicals, Inc.

Protocol adherence and the ability to achieve target haemoglobin levels in haemodialysis patients.

PubMed

Chan, Kevin; Moran, John; Hlatky, Mark; Lafayette, Richard

2009-06-01

Anemia management remains complicated in patients with endstage renal disease on hemodialysis. We wished to evaluate the effect of protocol adherence to EPO and intravenous iron dosing on achieving the desired range of hemoglobin levels. A cohort of hemodialysis patients was studied to evaluate the rate of adherence to EPO and iron dosing protocols over a 5 month period. A database was completed to evaluate all known comorbidities, demographic factors, and facility issues that might affect hemoglobin levels. A logistic regression model was employed to evaluate the effect of adherence to the anemia protocols on the probability of achieving a hemoglobin level below, within or above the targeted range of 11-12.5 g/dl. Among 2114 patients, we found that adherence to both the EPO and iron dosing protocol resulted in the greatest probability of achieving the target hemoglobin range (56 +/- 5% in anemia protocol adherent patients versus 42 +/- 7% in non adherent patients). This was predominantly due to a lowered risk of having above target hemoglobin levels rather than below. The use of the anemia protocols was associated with lower rates of hospitalization (9 +/- 0.7 visits/100 months in adherent group vs 15 +/- 2 in non adherent group) and lower utilization of both EPO and intravenous iron. Furthermore, patients in the adherent groups had less variability of their hemoglobin levels month by month, at least as judged by standard deviation. Adherence to anemia protocols, as practiced in the dialysis units included in this cohort, may improve hemodialysis patients' ability to achieve target hemoglobin levels, and by avoiding above target hemoglobin values, lower drug utilization and reduce variability of hemoglobin levels.

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

PubMed Central

Mousavi, Seyed Ali; Mahmood, Faiza; Aandahl, Astrid; Knutsen, Teresa Risopatron; Llohn, Abid Hussain

2015-01-01

Objectives. We aimed to examine whether baseline hemoglobin levels in C282Y-homozygous patients are related to the degree of serum ferritin (SF) elevation and whether patients with different baseline hemoglobin have different phlebotomy requirements. Methods. A total of 196 patients (124 males and 72 females) who had undergone therapeutic phlebotomy and had SF and both pre- and posttreatment hemoglobin values were included in the study. Results. Bivariate correlation analysis suggested that baseline SF explains approximately 6 to 7% of the variation in baseline hemoglobin. The results also showed that males who had higher (≥150 g/L) baseline hemoglobin levels had a significantly greater reduction in their posttreatment hemoglobin despite requiring fewer phlebotomies to achieve iron depletion than those who had lower (<150 g/L) baseline hemoglobin, regardless of whether baseline SF was below or above 1000 µg/L. There were no significant differences between hemoglobin subgroups regarding baseline and treatment characteristics, except for transferrin saturation between male subgroups with SF above 1000 µg/L. Similar differences were observed when females with higher (≥138 g/L) baseline hemoglobin were compared with those with lower (<138 g/L) baseline hemoglobin. Conclusion. Dividing C282Y-homozygous patients into just two subgroups according to the degree of baseline SF elevation may obscure important subgroup variations. PMID:26380265

Precision of noninvasive hemoglobin-level measurement by pulse co-oximetry in patients admitted to intensive care units for severe gastrointestinal bleeds.

PubMed

Coquin, Julien; Dewitte, Antoine; Manach, Yannick Le; Caujolle, Marie; Joannes-Boyau, Olivier; Fleureau, Catherine; Janvier, Gérard; Ouattara, Alexandre

2012-09-01

Measurement of total hemoglobin, based on pulse co-oximetry, is a continuous and noninvasive method that has been principally evaluated in healthy volunteers subjected to hemodilution. We tested the hypothesis that its accuracy could adversely affect patients presenting with severe hemorrhage, which is traditionally associated with increased microvascular tone. Observational study. Twelve-bed mixed medico-surgical intensive care unit. Thirty-three patients admitted to our critical care unit for gastrointestinal bleeds were included. A spectrophotometric sensor was positioned on the patient's fingertip and connected to a pulse co-oximeter. During the first 24 hrs following admission, venous hemoglobin level was determined at the laboratory every 8 hrs and was compared with hemoglobin levels displayed on the pulse co-oximeter measurements screen and/or measured from capillary blood using a portable photometer. The primary end point was the percentage of inaccurate measurements, which were defined as >15% difference compared with reference values or their unavailability for any technical reason. Twenty-five (19%) measurements of pulse co-oximeter measurements were unavailable from the screen. Pulse co-oximeter measurements and capillary hemoglobin levels were significantly correlated to venous hemoglobin level. For venous hemoglobin level compared with pulse co-oximeter measurements (n = 105), and for venous hemoglobin level compared with capillary hemoglobin levels (n = 111), the biases were, respectively, 1.0 ± 1.9 g dL and 0.4 ± 1.0 g dL (p < .05). The proportion of inaccurate measurements was significantly higher for pulse co-oximeter measurements (56% vs. 15%, p < .05). Although the use of norepinephrine did not affect concordance parameters, unavailability of measurements was frequently observed (42% vs. 15%, p < .05). Determination of pulse co-oximetry-based hemoglobin in patients presenting with severe gastrointestinal bleeds can be inaccurate, which renders its use to guide transfusion decisions potentially hazardous. The unavailability of measurements, especially during vasopressor infusion, represents another serious limitation for hemorrhagic patients.

Hepcidin-Induced Iron Deficiency Is Related to Transient Anemia and Hypoferremia in Kawasaki Disease Patients

PubMed Central

Huang, Ying-Hsien; Kuo, Ho-Chang; Huang, Fu-Chen; Yu, Hong-Ren; Hsieh, Kai-Sheng; Yang, Ya-Ling; Sheen, Jiunn-Ming; Li, Sung-Chou; Kuo, Hsing-Chun

2016-01-01

Kawasaki disease (KD) is a type of systemic vasculitis that primarily affects children under the age of five years old. For sufferers of KD, intravenous immunoglobulin (IVIG) has been found to successfully diminish the occurrence of coronary artery lesions. Anemia is commonly found in KD patients, and we have shown that in appropriately elevated hepcidin levels are related to decreased hemoglobin levels in these patients. In this study, we investigated the time period of anemia and iron metabolism during different stages of KD. A total of 100 patients with KD and 20 control subjects were enrolled in this study for red blood cell and hemoglobin analysis. Furthermore, plasma, urine hepcidin, and plasma IL-6 levels were evaluated using enzyme-linked immunosorbent assay in 20 KD patients and controls. Changes in hemoglobin, plasma iron levels, and total iron binding capacity (TIBC) were also measured in patients with KD. Hemoglobin, iron levels, and TIBC were lower (p < 0.001, p = 0.009, and p < 0.001, respectively) while plasma IL-6 and hepcidin levels (both p < 0.001) were higher in patients with KD than in the controls prior to IVIG administration. Moreover, plasma hepcidin levels were positively and significantly correlated with urine hepcidin levels (p < 0.001) prior to IVIG administration. After IVIG treatment, plasma hepcidin and hemoglobin levels significantly decreased (both p < 0.001). Of particular note was a subsequent gradual increase in hemoglobin levels during the three weeks after IVIG treatment; nevertheless, the hemoglobin levels stayed lower in KD patients than in the controls (p = 0.045). These findings provide a longitudinal study of hemoglobin changes and among the first evidence that hepcidin induces transient anemia and hypoferremia during KD’s acute inflammatory phase. PMID:27187366

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

PubMed Central

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

2015-01-01

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

A highly fluorescent hydrophilic ionic liquid as a potential probe for the sensing of biomacromolecules.

PubMed

Chen, Xu-Wei; Liu, Jia-Wei; Wang, Jian-Hua

2011-02-17

With respect to the conventional imidazolium ionic liquids which generally create very weak fluorescence with quantum yields at extremely low levels of 0.005-0.02, a symmetrical hydrophilic ionic liquid 1,3-butylimidazolium chloride (BBimCl) was found to be highly fluorescent with λ(em) at 388 nm when excited at λ(ex) < 340 nm. The very high quantum yield of BBimCl in aqueous medium, derived to be 0.523 when excited at 315 nm, was attributed to its symmetrical plane conjugating structure. In the presence of hemoglobin, the fluorescence of BBimCl could be significantly quenched, resulting from the coordinating interaction between the iron atom in the heme group of hemoglobin and the cationic imidazolium moiety. This feature of the present hydrophilic ionic liquid makes it a promising fluorescence probe candidate for the sensitive sensing of hemoglobin. A linear regression was observed within 3 × 10(-7) to 5 × 10(-6) mol L(-1) for hemoglobin, and a detection limit of 7.3 × 10(-8) mol L(-1) was derived.

Economic Analysis of the Reduction of Blood Transfusions during Surgical Procedures While Continuous Hemoglobin Monitoring Is Used

PubMed Central

Ribed-Sánchez, Borja; Varea-Díaz, Sara; Corbacho-Fabregat, Carlos; Pérez-Oteyza, Jaime; Belda-Iniesta, Cristóbal

2018-01-01

Background: Two million transfusions are performed in Spain every year. These come at a high economic price for the health system, increasing the morbidity and mortality rates. The way of obtaining the hemoglobin concentration value is via invasive and intermittent methods, the results of which take time to obtain. The drawbacks of this method mean that some transfusions are unnecessary. New continuous noninvasive hemoglobin measurement technology can save unnecessary transfusions. Methods: A prospective study was carried out with a historical control of two homogeneous groups. The control group used the traditional hemoglobin measurement methodology. The experimental group used the new continuous hemoglobin measurement technology. The difference was analyzed by comparing the transfused units of the groups. The economic savings was calculated by multiplying the cost of a transfusion by the difference in units, taking into account measurement costs. Results: The percentage of patients needing a transfusion decreased by 7.4%, and the number of transfused units per patient by 12.56%. Economic savings per patient were €20.59. At the national level, savings were estimated to be 13,500 transfusions (€1.736 million). Conclusions: Constant monitoring of the hemoglobin level significantly reduces the need for blood transfusions. By using this new measurement technology, health care facilities can significantly reduce costs and improve care quality. PMID:29702617

Maternal and Perinatal Outcomes in Second Hemoglobin Measurement in Nonanemic Women at First Booking: Effect of Altitude of Residence in Peru

PubMed Central

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 <19.9 kg/m2, living without partner, <5 antenatal care visits, first parity, multiparity, and preeclampsia. Lower risk for moderate/severe 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. PMID:22577573

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

PubMed

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 <19.9 kg/m(2), living without partner, <5 antenatal care visits, first parity, multiparity, and preeclampsia. Lower risk for moderate/severe 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.

Age and anemia management: relationship of hemoglobin levels with mortality might differ between elderly and nonelderly hemodialysis patients

PubMed Central

Hanafusa, Norio; Nomura, Takanobu; Hasegawa, Takeshi; Nangaku, Masaomi

2014-01-01

Background The elderly hemodialyzed population is growing. However, little is known about the relationship between hemoglobin level and survival according to age. We investigated the effect of age on the relationship between hemoglobin and survival within the Japan Dialysis Outcomes and Practice Patterns Study (DOPPS) cohort. Methods We enrolled the entire Japan DOPPS phases 3 and 4 population. Patients were divided by the age of 75 years into two groups. Cox's proportional hazard model was used with hemoglobin at every 4 months treated as a time-dependent variable. The interaction of age and hemoglobin was analyzed. Results We included 3341 patients in the analyses. The primary outcome occurred in 567 patients during the median follow-up of 2.64 years. Hemoglobin of entire population was 10.3 ± 1.3 g/dL. The median of epoetin dose was 3000 IU/week. Interaction was found between ages stratified by the age of 75 years and hemoglobin values (P = 0.045) with use of Cox's proportional hazard model. The nonelderly population had poorer prognosis with hemoglobin <10 g/dL, while elderly population only with hemoglobin <9 g/dL. For both hemoglobin strata <9, ≥9 and <10 g/dL, interactions between age and hemoglobin were significant. Subgroup analysis indicated that interaction between age and Hb levels was observed only in the nondiabetic nephropathy group. Several sensitivity analyses demonstrated a similar trend with the original analyses and reinforced the robustness. Conclusions The elderly population might tolerate low hemoglobin levels. Our findings open the way for further investigation of individualized anemia management. PMID:25150218

Hemoglobin levels triggering erythropoiesis-stimulating agent therapy in patients with cancer: the shift after United States Food and Drug Administration policy changes.

PubMed

Stroupe, Kevin T; Tarlov, Elizabeth; Lee, Todd A; Weichle, Thomas W; Zhang, Qiuying L; Michaelis, Laura C; Ozer, Howard; Durazo-Arvizu, Ramon; Browning, Margaret M; Hynes, Denise M

2012-11-01

To determine whether the hemoglobin level at which health care providers prescribed erythropoiesis-stimulating agent (ESA) therapy (trigger hemoglobin level) for their patients receiving chemotherapy was lower after the United States Food and Drug Administration (FDA) mandated a black-box warning in March 2007. Retrospective analysis. U.S. Department of Veterans Affairs Healthcare System (VA) national databases. A total of 7450 patients who were diagnosed with cancer between 2002 and 2009, were undergoing chemotherapy, and who received an ESA within 12 months after their cancer diagnosis. Data were collected on patients' demographic, clinical, environmental, and treatment-related factors. After controlling for these factors, multivariable regression analyses were used to compare the trigger hemoglobin level before and after the FDA-mandated labeling change. The average trigger hemoglobin level was 0.73 g/dl lower after the labeling change (95% confidence interval [CI] -0.84 to -0.63). Moreover, the decline in trigger hemoglobin levels began in mid-2006, when the average trigger hemoglobin level fell from 10.50 g/dl in early 2006 (95% CI 10.36-10.63) to 9.30 g/dl by late 2009 (95% CI 9.10-9.49). Even before the 2007 FDA-mandated changes in ESA product labeling, hemoglobin levels that triggered ESA treatment began declining for patients receiving cancer care within the VA. This highlights the critical importance of dissemination of postmarketing safety data to impact shifts in ESA use for anemia management. © 2012 Pharmacotherapy Publications, Inc.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rades, Dirk; Kuhn, Hildegard; Schultze, Juergen

2008-03-15

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

High Levels of Hemoglobin Promote Carotid Adventitial Vasa Vasorum Neoangiogenesis in Chronic Kidney Disease

PubMed Central

Martinez-Alonso, Montserrat; Belart, Montserrat; Vilar, Ana; Martín, Marisa; Craver, Lourdes; Betriu, Àngels; Valdivielso, José Manuel; Fernández, Elvira

2017-01-01

Chronic kidney disease (CKD) patients, characterized by traditional and nontraditional risk factors, are prone to develop atheromatosis and thus cardiovascular events and mortality. The angiogenesis of the adventitial vasa vasorum (aVV) surrounding the carotid has been described as the atheromatosis initiator. Therefore, the aim of the study was to (1) evaluate if the carotid aVV in CKD patients increases in comparison to its physiological value of healthy patients; (2) explore which traditional or nontraditional risk factor including inflammation, bone and mineral metabolism, and anemia could be related to the aVV angiogenesis. CKD patients without previous cardiovascular events (44, stages 3-4; 37, stage 5D) and 65 healthy subjects were compared. The carotid aVV and the intima-media thickness (cIMT) were evaluated by ultrasound. CKD patients at stages 3-4 showed higher aVV of the right carotid artery even after adjusting for age. Importantly, a multiple linear regression model showed hemoglobin levels > 12.5 g/dL as the factor for an estimated higher aVV of the right carotid artery. In conclusion, the association of hemoglobin with higher aVV could suggest the role of high hemoglobin in the higher incidence of adverse cardiovascular outcomes in CKD patients. PMID:28133420

Effects of intensive glucose lowering in type 2 diabetes.

PubMed

Gerstein, Hertzel C; Miller, Michael E; Byington, Robert P; Goff, David C; Bigger, J Thomas; Buse, John B; Cushman, William C; Genuth, Saul; Ismail-Beigi, Faramarz; Grimm, Richard H; Probstfield, Jeffrey L; Simons-Morton, Denise G; Friedewald, William T

2008-06-12

Epidemiologic studies have shown a relationship between glycated hemoglobin levels and cardiovascular events in patients with type 2 diabetes. We investigated whether intensive therapy to target normal glycated hemoglobin levels would reduce cardiovascular events in patients with type 2 diabetes who had either established cardiovascular disease or additional cardiovascular risk factors. In this randomized study, 10,251 patients (mean age, 62.2 years) with a median glycated hemoglobin level of 8.1% were assigned to receive intensive therapy (targeting a glycated hemoglobin level below 6.0%) or standard therapy (targeting a level from 7.0 to 7.9%). Of these patients, 38% were women, and 35% had had a previous cardiovascular event. The primary outcome was a composite of nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes. The finding of higher mortality in the intensive-therapy group led to a discontinuation of intensive therapy after a mean of 3.5 years of follow-up. At 1 year, stable median glycated hemoglobin levels of 6.4% and 7.5% were achieved in the intensive-therapy group and the standard-therapy group, respectively. During follow-up, the primary outcome occurred in 352 patients in the intensive-therapy group, as compared with 371 in the standard-therapy group (hazard ratio, 0.90; 95% confidence interval [CI], 0.78 to 1.04; P=0.16). At the same time, 257 patients in the intensive-therapy group died, as compared with 203 patients in the standard-therapy group (hazard ratio, 1.22; 95% CI, 1.01 to 1.46; P=0.04). Hypoglycemia requiring assistance and weight gain of more than 10 kg were more frequent in the intensive-therapy group (P<0.001). As compared with standard therapy, the use of intensive therapy to target normal glycated hemoglobin levels for 3.5 years increased mortality and did not significantly reduce major cardiovascular events. These findings identify a previously unrecognized harm of intensive glucose lowering in high-risk patients with type 2 diabetes. (ClinicalTrials.gov number, NCT00000620.) 2008 Massachusetts Medical Society

Effects of Intensive Glucose Lowering in Type 2 Diabetes

PubMed Central

2015-01-01

Background Epidemiologic studies have shown a relationship between glycated hemoglobin levels and cardiovascular events in patients with type 2 diabetes. We investigated whether intensive therapy to target normal glycated hemoglobin levels would reduce cardiovascular events in patients with type 2 diabetes who had either established cardiovascular disease or additional cardiovascular risk factors. Methods In this randomized study, 10,251 patients (mean age, 62.2 years) with a median glycated hemoglobin level of 8.1% were assigned to receive intensive therapy (targeting a glycated hemoglobin level below 6.0%) or standard therapy (targeting a level from 7.0 to 7.9%). Of these patients, 38% were women, and 35% had had a previous cardiovascular event. The primary outcome was a composite of nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes. The finding higher mortality in the intensive-therapy group led to a discontinuation of intensive therapy after a mean of 3.5 years of follow-up. Results At 1 year, stable median glycated hemoglobin levels of 6.4% and 7.5% were achieved in the intensive-therapy group and the standard-therapy group, respectively. During follow-up, the primary outcome occurred in 352 patients in the intensive-therapy group, as compared with 371 in the standard-therapy group (hazard ratio, 0.90; 95% confidence interval [CI], 0.78 to 1.04; P = 0.16). At the same time, 257 patients in the intensive-therapy group died, as compared with 203 patients in the standard-therapy group (hazard ratio, 1.22; 95% CI, 1.01 to 1.46; P = 0.04). Hypoglycemia requiring assistance and weight gain of more than 10 kg were more frequent in the intensive-therapy group (P<0.001). Conclusions As compared with standard therapy, the use of intensive therapy to target normal glycated hemoglobin levels for 3.5 years increased mortality and did not significantly reduce major cardiovascular events. These findings identify a previously unrecognized harm of intensive glucose lowering in high-risk patients with type 2 diabetes. (ClinicalTrials.gov number, NCT00000620.) PMID:18539917

Fecal hemoglobin excretion in elderly patients with atrial fibrillation: combined aspirin and low-dose warfarin vs conventional warfarin therapy.

PubMed

Blackshear, J L; Baker, V S; Holland, A; Litin, S C; Ahlquist, D A; Hart, R G; Ellefson, R; Koehler, J

1996-03-25

Antithrombotic prophylaxis using combined aspirin and low-dose warfarin is under evaluation in several clinical trials. However, therapy may result in increased gastrointestinal blood loss and clinical bleeding vs conventional single-agent antithrombotic therapy. To assess differences in gastrointestinal blood loss, we measured quantitative fecal hemoglobin equivalents (HemoQuant, Mayo Medical Laboratory, Rochester, Minn) in 117 patients, mean age 71 years, 1 month after initiation of assigned therapy in the Stroke Prevention in Atrial Fibrillation III Study. Sixty-three of these patients who had characteristics for high risk of stroke were randomly assigned to conventional adjusted-dose warfarin therapy (international normalized ratio, 2.0 to 3.0) or low-dose combined therapy (warfarin [international normalization ratio,<1.5] plus 325 mg/d of enteric-coated aspirin). The remaining 54 patients with low risk of stroke received 325 mg/d of enteric-coated aspirin. Among the 63 at high risk of stroke, abnormal values (>2mg of hemoglobin per gram of stool) were detected in 11% and values greater than 4 mg of hemoglobin per gram of stool were found in 8%. Mean ( +/- SD) values were more for those randomly assigned to receive combined therapy (1.7 +/- 3.3 mg of hemoglobin per gram of stool vs adjusted-dose warfarin therapy, 1.0 +/- 1.9 mg/g; P=.003). The 54 nonrandomized patients with low risk of stroke receiving aspirin alone had a mean (+/- SD) HemoQuant value of 0.8 +/- 0.7mg of hemoglobin per gram of stool 1 month after entry in the study. Abnormal levels of fecal hemoglobin excretion were common in elderly patients with high risk of atrial fibrillation 1 month after randomization to prophylactic antithrombotic therapy. Combined warfarin and aspirin therapy was associated with greater fecal hemoglobin excretion than standard warfarin therapy, suggesting the potential for increased gastrointestinal hemorrhage.

Pitfalls in the biological diagnosis of common hemoglobin disorders.

PubMed

Wajcman, Henri; Moradkhani, Kamran

2015-01-01

In West-European countries, hemoglobin disorders are no more rare diseases. Programs for diagnosis of heterozygous carriers have been established to prevent cases with major sickle cell disease or thalassemias. These studies have been done essentially by high performance liquid chromatography on cation-exchange columns and electrophoresis (mostly capillary electrophoresis). They have been done through systematic population studies or premarital diagnosis. We describe in this work the frequent or rare pitfalls encountered, which led to false negative or positive diagnosis both in the field of sickle cell disease and thalassemias. In the absence of a well identified hemoglobin disorder in the proband's family, it is a rule that the use of a single test is insufficient to identify formally HbS. The presence of HbS could also be masked by another hemoglobin abnormality. The sole measurement of HbA2 level is insufficient to characterize a thalassemic trait: this level needs always to be interpreted considering RBC parameters and iron metabolic status. In difficult cases, the definitive answer may require a family study and/or a molecular genetic characterization.

Hemoglobin Levels Across the Pediatric Critical Care Spectrum: A Point Prevalence Study.

PubMed

Hassan, Nabil E; Reischman, Diann E; Fitzgerald, Robert K; Faustino, Edward Vincent S

2018-05-01

To determine the prevailing hemoglobin levels in PICU patients, and any potential correlates. Post hoc analysis of prospective multicenter observational data. Fifty-nine PICUs in seven countries. PICU patients on four specific days in 2012. None. Patients' hemoglobin and other clinical and institutional data. Two thousand three hundred eighty-nine patients with median age of 1.9 years (interquartile range, 0.3-9.8 yr), weight 11.5 kg (interquartile range, 5.4-29.6 kg), and preceding PICU stay of 4.0 days (interquartile range, 1.0-13.0 d). Their median hemoglobin was 11.0 g/dL (interquartile range, 9.6-12.5 g/dL). The prevalence of transfusion in the 24 hours preceding data collection was 14.2%. Neonates had the highest hemoglobin at 13.1 g/dL (interquartile range, 11.2-15.0 g/dL) compared with other age groups (p < 0.001). The percentage of 31.3 of the patients had hemoglobin of greater than or equal to 12 g/dL, and 1.1% had hemoglobin of less than 7 g/dL. Blacks had lower median hemoglobin (10.5; interquartile range, 9.3-12.1 g/dL) compared with whites (median, 11.1; interquartile range, 9.0-12.6; p < 0.001). Patients in Spain and Portugal had the highest median hemoglobin (11.4; interquartile range, 10.0-12.6) compared with other regions outside of the United States (p < 0.001), and the highest proportion (31.3%) of transfused patients compared with all regions (p < 0.001). Patients in cardiac PICUs had higher median hemoglobin than those in mixed PICUs or noncardiac PICUs (12.3, 11.0, and 10.6 g/dL, respectively; p < 0.001). Cyanotic heart disease patients had the highest median hemoglobin (12.6 g/dL; interquartile range, 11.1-14.5). Multivariable regression analysis within diagnosis groups revealed that hemoglobin levels were significantly associated with the geographic location and history of complex cardiac disease in most of the models. In children with cancer, none of the variables tested correlated with patients' hemoglobin levels. Patients' hemoglobin levels correlated with demographics like age, race, geographic location, and cardiac disease, but none found in cancer patients. Future investigations should account for the effects of these variables.

Cinnamon extract improves fasting blood glucose and glycosylated hemoglobin level in Chinese patients with type 2 diabetes.

PubMed

Lu, Ting; Sheng, Hongguang; Wu, Johnna; Cheng, Yuan; Zhu, Jianming; Chen, Yan

2012-06-01

For thousands of years, cinnamon has been used as a traditional treatment in China. However, there are no studies to date that investigate whether cinnamon supplements are able to aid in the treatment of type 2 diabetes in Chinese subjects. We hypothesized cinnamon should be effective in improving blood glucose control in Chinese patients with type 2 diabetes. To address this hypothesis, we performed a randomized, double-blinded clinical study to analyze the effect of cinnamon extract on glycosylated hemoglobin A(1c) and fasting blood glucose levels in Chinese patients with type 2 diabetes. A total of 66 patients with type 2 diabetes were recruited and randomly divided into 3 groups: placebo and low-dose and high-dose supplementation with cinnamon extract at 120 and 360 mg/d, respectively. Patients in all 3 groups took gliclazide during the entire 3 months of the study. Both hemoglobin A(1c) and fasting blood glucose levels were significantly reduced in patients in the low- and high-dose groups, whereas they were not changed in the placebo group. The blood triglyceride levels were also significantly reduced in the low-dose group. The blood levels of total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and liver transaminase remained unchanged in the 3 groups. In conclusion, our study indicates that cinnamon supplementation is able to significantly improve blood glucose control in Chinese patients with type 2 diabetes. Copyright © 2012 Elsevier Inc. All rights reserved.

Genetic convergence in the adaptation of dogs and humans to the high-altitude environment of the tibetan plateau.

PubMed

Wang, Guo-Dong; Fan, Ruo-Xi; Zhai, Weiwei; Liu, Fei; Wang, Lu; Zhong, Li; Wu, Hong; Yang, He-Chuan; Wu, Shi-Fang; Zhu, Chun-Ling; Li, Yan; Gao, Yun; Ge, Ri-Li; Wu, Chung-I; Zhang, Ya-Ping

2014-08-01

The high-altitude hypoxic environment represents one of the most extreme challenges for mammals. Previous studies of humans on the Tibetan plateau and in the Andes Mountains have identified statistical signatures of selection in different sets of loci. Here, we first measured the hemoglobin levels in village dogs from Tibet and those from Chinese lowlands. We found that the hemoglobin levels are very similar between the two groups, suggesting that Tibetan dogs might share similar adaptive strategies as the Tibetan people. Through a whole-genome sequencing approach, we have identified EPAS1 and HBB as candidate genes for the hypoxic adaptation on the Tibetan plateau. The population genetic analysis shows a significant convergence between humans and dogs in Tibet. The similarities in the sets of loci that exhibit putative signatures of selection and the hemoglobin levels between humans and dogs of the same environment, but not between human populations in different regions, suggests an extraordinary landscape of convergent evolution between human beings and their best friend on the Tibetan plateau. © The Author(s) 2014. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

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

PubMed

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

2015-12-01

Induction of fetal hemoglobin (HbF) is considered a promising strategy in the treatment of β-thalassemia, in which production of adult hemoglobin (HbA) is impaired by mutations affecting the β-globin gene. Recent results indicate that B-cell lymphoma/leukemia 11A (BCL11A) is a major repressor of γ-globin gene expression. Therefore, disrupting the binding of the BCL11A transcriptional repressor complex to the γ-globin gene promoter provides a novel approach for inducing expression of the γ-globin genes. To develop a cellular screening system for the identification of BCL11A inhibitors, we produced K562 cell clones with integrated copies of a BCL11A-XL expressing vector. We characterized 12 K562 clones expressing different levels of BCL11A-XL and found that a clear inverse relationship does exist between the levels of BCL11A-XL and the extent of hemoglobinization induced by a panel of HbF inducers. Using mithramycin as an inducer, we found that this molecule was the only HbF inducer efficient in rescuing the ability to differentiate along the erythroid program, even in K562 cell clones expressing high levels of BCL11A-XL, suggesting that BCL11A-XL activity is counteracted by mithramycin. Copyright © 2015 ISEH - International Society for Experimental Hematology. Published by Elsevier Inc. All rights reserved.

The Greenland shark Somniosus microcephalus-Hemoglobins and ligand-binding properties.

PubMed

Russo, Roberta; Giordano, Daniela; Paredi, Gianluca; Marchesani, Francesco; Milazzo, Lisa; Altomonte, Giovanna; Del Canale, Pietro; Abbruzzetti, Stefania; Ascenzi, Paolo; di Prisco, Guido; Viappiani, Cristiano; Fago, Angela; Bruno, Stefano; Smulevich, Giulietta; Verde, Cinzia

2017-01-01

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.

The Greenland shark Somniosus microcephalus—Hemoglobins and ligand-binding properties

PubMed Central

Paredi, Gianluca; Marchesani, Francesco; Milazzo, Lisa; Altomonte, Giovanna; Del Canale, Pietro; Abbruzzetti, Stefania; Ascenzi, Paolo; di Prisco, Guido; Viappiani, Cristiano; Fago, Angela; Bruno, Stefano; Smulevich, Giulietta

2017-01-01

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. PMID:29023598

The mechanism of formation, structure and physiological relevance of covalent hemoglobin attachment to the erythrocyte membrane.

PubMed

Welbourn, Elizabeth M; Wilson, Michael T; Yusof, Ashril; Metodiev, Metodi V; Cooper, Chris E

2017-02-01

Covalent hemoglobin binding to membranes leads to band 3 (AE1) clustering and the removal of erythrocytes from the circulation; it is also implicated in blood storage lesions. Damaged hemoglobin, with the heme being in a redox and oxygen-binding inactive hemichrome form, has been implicated as the binding species. However, previous studies used strong non-physiological oxidants. In vivo hemoglobin is constantly being oxidised to methemoglobin (ferric), with around 1% of hemoglobin being in this form at any one time. In this study we tested the ability of the natural oxidised form of hemoglobin (methemoglobin) in the presence or absence of the physiological oxidant hydrogen peroxide to initiate membrane binding. The higher the oxidation state of hemoglobin (from Fe(III) to Fe(V)) the more binding was observed, with approximately 50% of this binding requiring reactive sulphydryl groups. The hemoglobin bound was in a high molecular weight complex containing spectrin, ankyrin and band 4.2, which are common to one of the cytoskeletal nodes. Unusually, we showed that hemoglobin bound in this way was redox active and capable of ligand binding. It can initiate lipid peroxidation showing the potential to cause cell damage. In vivo oxidative stress studies using extreme endurance exercise challenges showed an increase in hemoglobin membrane binding, especially in older cells with lower levels of antioxidant enzymes. These are then targeted for destruction. We propose a model where mild oxidative stress initiates the binding of redox active hemoglobin to the membrane. The maximum lifetime of the erythrocyte is thus governed by the redox activity of the cell; from the moment of its release into the circulation the timer is set. Copyright © 2016. Published by Elsevier Inc.

Effects of growth, diving history, and high altitude on blood oxygen capacity in harbor seals

NASA Technical Reports Server (NTRS)

Kodama, A. M.; Elsner, R.; Pace, N.

1977-01-01

Blood volume and body composition for diving and nondiving harbor seals were measured at six-week intervals during a 10-month period of captitivity. Whole body hematocrit, red cell volume per kg of lean body mass, and total circulating hemoglobin per kg lean body mass were significantly higher in the diving group, but relatively large blood volumes expressed in terms of body weight (11-12%) were found in both groups. A pair of harbor seals exposed to high altitude for about three months registered significant increases in red cell volume, blood hemoglobin levels, and blood volume expressed in terms of body weight; results of alveolar gas analyses indicate that hyperventilation also occurred. These typical mammalian responses to hypoxia suggest that the harbor seal's large blood volume and high hemoglobin content are an expression of phylogenetic control, and that in spite of its adaptability to apnea during its diving life, the animal cannot be considered preacclimatized to high altitude.

Exposure to fluoride in smelter workers in a primary aluminum industry in India.

PubMed

Susheela, A K; Mondal, N K; Singh, A

2013-04-01

Fluoride is used increasingly in a variety of industries in India. Emission of fluoride dust and fumes from the smelters of primary aluminum producing industries is dissipated in the work environment and poses occupational health hazards. To study the prevalence of health complaints and its association with fluoride level in body fluids of smelter workers in a primary aluminum producing industry. In an aluminum industry, health status of 462 smelter workers, 60 supervisors working in the smelter unit, 62 non-smelter workers (control group 1) and 30 administration staff (control group 2) were assessed between 2007 and 2009. Their health complaints were recorded and categorized into 4 groups: 1) gastro-intestinal complaints; 2) non-skeletal manifestations; 3) skeletal symptoms; and (4) respiratory problems. Fluoride level in body fluids, nails, and drinking water was tested by an ion selective electrode; hemoglobin level was tested using HemoCue. The total complaints reported by study groups were significantly higher than the control groups. Smelter workers had a significantly (p<0.001) higher urinary and serum fluoride level than non-smelter workers; the nail fluoride content was also higher in smelter workers than non-smelter workers (p<0.001). The smelter workers with higher hemoglobin level had a significantly (p<0.001) lower urinary fluoride concentration and complained less frequently of health problems. Only 1.4% of the smelter workers were consuming water with high fluoride concentrations. A high percentage of participants was using substances with high fluoride contents. Industrial emission of fluoride is not the only important sources of fluoride exposure--consumption of substance with high levels of fluoride is another important route of entry of fluoride into the body. Measurement of hemoglobin provides a reliable indicator for monitoring the health status of employees at risk of fluorosis.

Chromatofocusing and isoelectric focusing in immobilized pH gradients compared for characterization of human hemoglobin variants.

PubMed

Paleari, R; Arcelloni, C; Paroni, R; Fermo, I; Mosca, A

1989-03-01

We compared the performance of two highly resolving methods, chromatofocusing (CRF) and isoelectric focusing in immobilized pH gradients (IPGF), for the separation of human hemoglobin variants. Lysates containing 13 different hemoglobins, including variants of clinical and geographical importance, and four electrophoretically "silent" variants (Hb Brockton, Hb Cheverly, Hb Köln, and Hb Waco) were analyzed. Both techniques showed a good intrarun precision (CV = 0.87% for CRF, 0.27% for IPGF) and high and similar resolving power (0.010 pH units, with the pH gradients used in this work). The use of an ultranarrow IPGF range (pH 7.15-7.35; pH gradient = 0.019 pH/cm) allowed the resolution between Hb Brockton, Hb Köln, and Hb A. In some cases (Hb D-Los Angeles, Hb F, Hb Waco), the variants were separated from Hb A in different orders, depending on which technique was used, probably because of the different analytical principles of the two methods. As a second-level test, both procedures are informative for characterization of human hemoglobin variants.

Hydroxyurea therapy requires HbF induction for clinical benefit in a sickle cell mouse model

PubMed Central

Lebensburger, Jeffrey D.; Pestina, Tamara I.; Ware, Russell E.; Boyd, Kelli L.; Persons, Derek A.

2010-01-01

Hydroxyurea has proven clinical efficacy in patients with sickle cell disease. Potential mechanisms for the beneficial effects include fetal hemoglobin induction and the reduction of cell adhesive properties, inflammation and hypercoagulability. Using a murine model of sickle cell disease in which fetal hemoglobin induction does not occur, we evaluated whether hydroxyurea administration would still yield improvements in hematologic parameters and reduce end-organ damage. Animals given a maximally tolerated dose of hydroxyurea that resulted in significant reductions in the neutrophil and platelet counts showed no improvement in hemolytic anemia and end-organ damage compared to control mice. In contrast, animals having high levels of fetal hemoglobin due to gene transfer with a γ-globin lentiviral vector showed correction of anemia and organ damage. These data suggest that induction of fetal hemoglobin by hydroxyurea is an essential mechanism for its clinical benefits. PMID:20378564

Differences in hemoglobin adduct levels of acrylamide in the general population with respect to dietary intake, smoking habits and gender.

PubMed

Hagmar, Lars; Wirfält, Elisabet; Paulsson, Birgit; Törnqvist, Margareta

2005-02-07

The variation in dietary exposure to acrylamide (AA) has been studied through measurement of hemoglobin adduct levels from AA, as a measurement of internal dose, in a sample from the blood bank of the Malmö Diet and Cancer Cohort (n=28,098). The blood donors are well characterised with regard to their food habits, and 142 individuals were selected to obtain highest possible variation in the adduct levels from AA (none, random or high intake of coffee, fried potato, crisp bread and snacks, food items estimated to have high levels of AA). Among 70 non-smokers the AA-adduct levels varied by a factor of 5, and ranged between 0.02 and 0.1 nmol/g, with considerable overlap in AA-adduct levels between the different dietary groups. There was a significant difference between men with high dietary exposure to AA compared to men with low dietary exposure (P=0.04). No such difference was found for women. As expected a higher level (range: 0.03-0.43 nmol/g) of the AA-adduct, due to AA in tobacco smoke, was found in smokers. Smoking women with high dietary exposure to AA had significantly higher AA-adduct levels compared to smoking women with low dietary exposure (P=0.01). No such significant difference was found in smoking men. The median hemoglobin (Hb) adduct level in the randomly selected group of non-smokers was compatible with earlier studies (0.031 nmol/g). The variation in the average internal dose, measured as Hb adducts, was somewhat smaller than estimated for daily intake by food consumption questionnaires in other studies. Thus, the observed relatively narrow inter-individual variation in AA-adduct levels means that estimates of individual dietary AA intake have to be very precise if they should be useful in future cancer epidemiology.

Patterns of glycemic control using glycosylated hemoglobin in diabetics.

PubMed

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 significant (P = .007). Sixty-five percent of the case had IDRS higher than 60. Glycaemic control in diabetics can be better assessed with glycosylated hemoglobin and FPG together. A positive correlation between FPG and HbA1c allows for the use of HbA1c along with FPG in diagnosing type 2 DM but the two should not be used interchangeably. IDRS can be used as a screening tool for diabetes.

Hemoglobin Wayne Trait with Incidental Polycythemia.

PubMed

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

2017-01-01

Hemoglobinopathies, caused by mutations in the globin genes, are one of the most common inherited disorders. Many of the hemoglobin variants can be identified by hemoglobin analysis using conventional electrophoresis and high performance liquid chromatography; however hemoglobin DNA analysis may be necessary in other cases for confirmation. Here, we report a case of a rare alpha chain hemoglobin variant, hemoglobin Wayne, in a 47-year-old man who presented with secondary polycythemia. Capillary zone electrophoresis and high performance liquid chromatography revealed a significant amount of a hemoglobin variant, which was further confirmed by hemoglobin DNA sequencing as hemoglobin Wayne. Since the patient was not homozygous for hemoglobin Wayne, which is associated with secondary polycythemia, the laboratory diagnosis in this case was critical in ruling out hemoglobinopathy as the etiology of his polycythemia. © 2017 by the Association of Clinical Scientists, Inc.

Positive Association of Vitamin E Supplementation with Hemoglobin Levels in Mildly Anemic Healthy Pakistani Adults.

PubMed

Jilani, Tanveer; Azam, Iqbal; Moiz, Bushra; Mehboobali, Naseema; Perwaiz Iqbal, Mohammad

2015-01-01

Hemoglobin levels slightly below the lower limit of normal are common in adults in the general population in developing countries. A few human studies have suggested the use of antioxidant vitamins in the correction of mild anemia. The objective of the present study was to investigate the association of vitamin E supplementation in mildly anemic healthy adults with post-supplemental blood hemoglobin levels in the general population of Karachi, Pakistan. In a single-blinded and placebo-controlled randomized trial, 124 mildly anemic subjects from the General Practitioners' Clinics and personnel of the Aga Khan University were randomized into intervention (n = 82) and control (n = 42) group. In the intervention group, each subject was given vitamin E (400 mg) everyday for a period of three months, while control group subjects received a placebo. Eighty six subjects completed the trial. Fasting venous blood was collected at baseline and after three months of supplementation. Hemoglobin levels and serum/plasma concentrations of vitamin E, vitamin B12, folate, ferritin, serum transferrin receptor (sTfR), glucose, total cholesterol, triglycerides, LDL-cholesterol, HDL-cholesterol, creatinine, total-antioxidant-status and erythropoietin were measured and analyzed using repeated measures ANOVA and multiple linear regression. The adjusted regression coefficients (β) and standard error [SE(β)] of the significant predictors of post-supplemental hemoglobin levels were serum concentration of vitamin E (0.983[0.095]), gender (- 0.656[0.244]), sTfR (- 0.06[0.02]) and baseline hemoglobin levels (0.768[0.077]). The study showed a positive association between vitamin E supplementation and enhanced hemoglobin levels in mildly anemic adults.

Elevated lead levels and changes in blood morphology and erythrocyte CR1 in preschool children from an e-waste area.

PubMed

Dai, Yifeng; Huo, Xia; Zhang, Yu; Yang, Tian; Li, Minghui; Xu, Xijin

2017-08-15

Improper dismantling and combustion of electronic waste (e-waste) may release persistent organic pollutants and heavy metals that possess potential risk for human health. Lead (Pb) is carried through the circulatory system by erythrocytes and is known to alter the functions of hematopoietic and immune systems. The aim of the study was to investigate the effect of Pb exposure on blood morphology and erythrocyte complement receptor 1 (CR1) levels as related to immunologic function in preschool children. We recruited 484 preschool children, 2- to 6-years of age, among whom 332 children were from Guiyu, a typical and primitive e-waste processing area, and 152 children from Haojiang (reference area). Results showed that the blood Pb level (BPb) and erythrocyte Pb level (EPb) of exposed children were significantly higher, but, the mean corpuscular hemoglobin concentration (MCHC) and erythrocyte CR1 levels were significantly lower than reference children. Elevated EPb and BPb was related to disadvantageous changes in hematocrit (HCT), mean corpuscular volume (MCV), hemoglobin (HGB), mean corpuscular hemoglobin (MCH), and MCHC, respectively, in children from the e-waste recycling area. Furthermore, in the high Pb-exposed group, the Pb toxicity of erythrocytes was more significant compared to the low Pb-exposed group in e-waste-exposed children. Combine with the BPb and EPb would be better to evaluating the Pb toxicity of erythrocytes. Compared to low Pb exposure, high BPb and EPb were associated with lower erythrocyte CR1 expression in all children. Our data suggests that elevated Pb levels result in adverse changes in blood morphology, hemoglobin synthesis and CR1 expression, which might be a non-negligible threat to erythrocyte immunity development in local preschool children. It is therefore imperative for any intervention to control the Pb exposure of children and actively educate adults to raise their environmental awareness of potential e-waste pollution during the recycling process. Copyright © 2017 Elsevier B.V. All rights reserved.

Acceptability, Safety, and Efficacy of Oral Administration of Extracts of Black or Red Maca (Lepidium meyenii) in Adult Human Subjects: A Randomized, Double-Blind, Placebo-Controlled Study

PubMed Central

Gonzales-Arimborgo, Carla; Yupanqui, Irma; Montero, Elsa; Alarcón-Yaquetto, Dulce E.; Zevallos-Concha, Alisson; Caballero, Lidia; Gasco, Manuel; Zhao, Jianping; Khan, Ikhlas A.; Gonzales, Gustavo F.

2016-01-01

The plant maca, grown at 4000 m altitude in the Peruvian Central Andes, contains hypocotyls that have been used as food and in traditional medicine for centuries. The aim of this research was to provide results on some health effects of oral administration of spray-dried extracts of black or red maca (Lepidium meyenii) in adult human subjects living at low (LA) and high altitude (HA). A total of 175 participants were given 3 g of either placebo, black, or red maca extract daily for 12 weeks. Primary outcomes were changes in sexual desire, mood, energy, health-related quality of life score (HRQL), and chronic mountain sickness (CMS) score, or in glycaemia, blood pressure, and hemoglobin levels. Secondary outcomes were acceptability and safety, assessed using the Likert test and side effect self-recording, respectively, and the effect of altitude. At low altitude, 32, 30, and 32 participants started the study receiving placebo, red maca, or black maca, respectively. At high altitudes, 33, 35, and 31 participants started the study receiving placebo, red maca, and black maca, respectively. Consumption of spray-dried extracts of red and black maca resulted in improvement in mood, energy, and health status, and reduced CMS score. Fatty acids and macamides were higher in spray-dried extracts of black maca than in red maca. GABA predominated in spray-dried extracts of red maca. Effects on mood, energy, and CMS score were better with red maca. Black maca and, in smaller proportions, red maca reduced hemoglobin levels only in highlanders with abnormally high hemoglobin levels; neither variety of maca reduced hemoglobin levels in lowlanders. Black maca reduced blood glucose levels. Both varieties produced similar responses in mood, and HRQL score. Maca extracts consumed at LA or HA had good acceptability and did not show serious adverse effects. In conclusion, maca extract consumption relative to the placebo improved quality of life parameters. Differences in the level of improvement between red and black maca are probably due to differences in the composition of these two plant varieties. Both maca extracts were well tolerated and safe. PMID:27548190

Acceptability, Safety, and Efficacy of Oral Administration of Extracts of Black or Red Maca (Lepidium meyenii) in Adult Human Subjects: A Randomized, Double-Blind, Placebo-Controlled Study.

PubMed

Gonzales-Arimborgo, Carla; Yupanqui, Irma; Montero, Elsa; Alarcón-Yaquetto, Dulce E; Zevallos-Concha, Alisson; Caballero, Lidia; Gasco, Manuel; Zhao, Jianping; Khan, Ikhlas A; Gonzales, Gustavo F

2016-08-18

The plant maca, grown at 4000 m altitude in the Peruvian Central Andes, contains hypocotyls that have been used as food and in traditional medicine for centuries. The aim of this research was to provide results on some health effects of oral administration of spray-dried extracts of black or red maca (Lepidium meyenii) in adult human subjects living at low (LA) and high altitude (HA). A total of 175 participants were given 3 g of either placebo, black, or red maca extract daily for 12 weeks. Primary outcomes were changes in sexual desire, mood, energy, health-related quality of life score (HRQL), and chronic mountain sickness (CMS) score, or in glycaemia, blood pressure, and hemoglobin levels. Secondary outcomes were acceptability and safety, assessed using the Likert test and side effect self-recording, respectively, and the effect of altitude. At low altitude, 32, 30, and 32 participants started the study receiving placebo, red maca, or black maca, respectively. At high altitudes, 33, 35, and 31 participants started the study receiving placebo, red maca, and black maca, respectively. Consumption of spray-dried extracts of red and black maca resulted in improvement in mood, energy, and health status, and reduced CMS score. Fatty acids and macamides were higher in spray-dried extracts of black maca than in red maca. GABA predominated in spray-dried extracts of red maca. Effects on mood, energy, and CMS score were better with red maca. Black maca and, in smaller proportions, red maca reduced hemoglobin levels only in highlanders with abnormally high hemoglobin levels; neither variety of maca reduced hemoglobin levels in lowlanders. Black maca reduced blood glucose levels. Both varieties produced similar responses in mood, and HRQL score. Maca extracts consumed at LA or HA had good acceptability and did not show serious adverse effects. In conclusion, maca extract consumption relative to the placebo improved quality of life parameters. Differences in the level of improvement between red and black maca are probably due to differences in the composition of these two plant varieties. Both maca extracts were well tolerated and safe.

Detection of Hemoglobin New York [β113 (G15) Val→Glu, GTG>GAG] in a Thai Woman by Capillary Electrophoresis.

PubMed

Panyasai, Sitthichai; Pornprasert, Sakorn

2016-12-01

Hemoglobin (Hb) New York [β113 (G15) Val→Glu, GTG>GAG] is a very rare β-chain variant found in Thailand. This variant is often missed by routine laboratory testing because Hb New York and Hb A have the identical retention time on high performance liquid chromatography. We reported here for the first time that the detection of Hb New York in a Thai woman by using capillary electrophoresis (CE). A peak of Hb New York located ahead of Hb A at the electrophoretic zone 11 with a level of 42.8 %. The DNA sequencing revealed the GTG>GAG mutation at codon 113 for Hb New York on one allele of β-globin gene. Therefore, the CE has a high efficiency to prevent the misinterpretation of hemoglobin analysis in patients who are heterozygote of this variant.

Association between serum ferritin and hemoglobin levels and bone health in Korean adolescents

PubMed Central

Jung, Dong-Wook; Park, Joo-Hyun; Kim, Do-Hoon; Choi, Moonyoung; Kim, Shinhye; Kim, Hyonchong; Seul, Da-eun; Park, Soo Gyeong; Jung, Jin-Hyung; Han, Kyungdo; Park, Young-Gyu

2017-01-01

Abstract It is important to identify risk factors for low bone mass at a young age. An influence of iron store on bone health in the general population has been reported but has not been studied in adolescents. This study aimed to investigate the relationship between hemoglobin and serum ferritin levels and bone mineral content (BMC) in South Korean adolescents. This study was based on data collected during the 2009to 2010 Korea National Health and Nutrition Examination Survey. We included 1321 participants aged 10 to 18 years. BMC was measured at the femur and lumbar spine using dual-energy x-ray absorptiometry, and hemoglobin and serum ferritin levels were examined. In boys, hemoglobin and serum ferritin levels were positively associated with BMC of the total femur and lumbar spine after adjusting for confounders, and hemoglobin levels significantly increased as BMC increased at all sites (P for trend = .001 for total femur, .01 for femur neck, and <.001 for lumbar spine). Likewise, serum ferritin levels showed increasing trends according to increasing BMC of the total femur and lumbar spine in boys (P for trend = .04 for total femur; and <.001 for lumbar spine). However, these associations were not observed in girls. This study suggests a positive relationship between serum ferritin and hemoglobin levels and BMC in South Korean adolescent boys. PMID:29390554

Fetal hemoglobin regulation in β-thalassemia: heterogeneity, modifiers and therapeutic approaches.

PubMed

Sripichai, Orapan; Fucharoen, Suthat

2016-12-01

Stress erythropoiesis induces fetal hemoglobin (HbF) expression in β-thalassemias, however the level of expression is highly variable. The last decade has seen dramatic advances in our understanding of the molecular regulators of HbF production and the genetic factors associated with HbF levels, leading to the promise of new methods of the clinical induction of HbF. Areas covered: This article will review the heterogeneity and genetic modifiers of HbF and HbF induction therapy in β-thalassemia. Expert commentary: One promising curative β-thalassemia therapy is to induce HbF synthesis in β-thalassemic erythrocytes to therapeutic levels before clinical symptom occurs. Further understanding of HbF level variation and regulation is needed in order to predict the response from HbF-inducing approaches.

Impact of preoperative levels of hemoglobin and albumin on the survival of pancreatic carcinoma.

PubMed

Ruiz-Tovar, J; Martín-Pérez, E; Fernández-Contreras, M E; Reguero-Callejas, M E; Gamallo-Amat, C

2010-11-01

Pancreatic cancer presents the worst survival rates of all neoplasms. Surgical resection is the only potentially curative treatment, but is associated with high complication rates and outcome is bad even in those resected cases. Therefore, candidates amenable for resection must be carefully selected. Identification of prognostic factors preoperatively may help to improve the treatment of these patients, focusing on individually management based on the expected response. We perform a retrospective study of 59 patients with histological diagnosis of pancreatic carcinoma between 1999 and 2003, looking for possible prognostic factors. We analyze 59 patients, 32 males and 27 females with a mean age of 63.8 years. All the patients were operated, performing palliative surgery in 32% and tumoral resection in 68%, including pancreaticoduodenectomies in 51% and distal pancreatectomy in 17%. Median global survival was 14 months (Range 1-110).We observed that preoperative levels of hemoglobin under 12 g/dl (p = 0.0006) and serum albumina under 2.8 g/dl (p = 0.021) are associated with worse survival. Preoperative levels of hemoglobin and serum albumina may be prognostic indicators in pancreatic cancer.

Hemoglobins, programmed cell death and somatic embryogenesis.

PubMed

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

2013-10-01

Programmed cell death (PCD) is a universal process in all multicellular organisms. It is a critical component in a diverse number of processes ranging from growth and differentiation to response to stress. Somatic embryogenesis is one such process where PCD is significantly involved. Nitric oxide is increasingly being recognized as playing a significant role in regulating PCD in both mammalian and plant systems. Plant hemoglobins scavenge NO, and evidence is accumulating that events that modify NO levels in plants also affect hemoglobin expression. Here, we review the process of PCD, describing the involvement of NO and plant hemoglobins in the process. NO is an effector of cell death in both plants and vertebrates, triggering the cascade of events leading to targeted cell death that is a part of an organism's response to stress or to tissue differentiation and development. Expression of specific hemoglobins can alter this response in plants by scavenging the NO, thus, interrupting the death process. Somatic embryogenesis is used as a model system to demonstrate how cell-specific expression of different classes of hemoglobins can alter the embryogenic process, affecting hormone synthesis, cell metabolite levels and genes associated with PCD and embryogenic competence. We propose that plant hemoglobins influence somatic embryogenesis and PCD through cell-specific expression of a distinct plant hemoglobin. It is based on the premise that both embryogenic competence and PCD are strongly influenced by cellular NO levels. Increases in cellular NO levels result in elevated Zn(2+) and reactive-oxygen species associated with PCD, but they also result in decreased expression of MYC2, a transcription factor that is a negative effector of indoleacetic acid synthesis, a hormone that positively influences embryogenic competence. Cell-specific hemoglobin expression reduces NO levels as a result of NO scavenging, resulting in cell survival. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Variation in hemoglobin concentration among samples of high-altitude natives in the Andes and the Himalayas.

PubMed

Beall, Cynthia M; Brittenham, Gary M; Macuaga, Francisco; Barragan, Mario

1990-01-01

This paper presents data on hemoglobin concentration in a rural Andean sample at 3,800-3,900 m and incorporates them into a review intended to evaluate possible sources of the range of variation in mean hemoglobin concentration among samples obtained at high altitude. Between 3,400 and 4,000 m, rural Himalayan highlanders average 1.4 gm/dl lower mean hemoglobin concentration than rural Andean highlanders. With respect to potential causes of anemia, it is concluded that the relatively low values of rural Himalyan populations are not explicable by lower hypoxic stress or different techniques of obtaining and analyzing blood samples and are probably not explicable by nutritional deficiency and disease. With respect to potential causes of polycythemia within Andean populations, it is concluded that the somewhat higher values of some mining and urban samples of Andean higlanders may not be due to the mining occupation per se but may be due partly to the inclusion of European and mestizo (with at most 500 years of high-altitude ancestry) along with Amerindian highlanders (with millenia of high-altitude ancestry) as well as to the inclusion of highlanders living well above their own habitual altitudes of residence. The Andean polycythemia is probably not due to obesity, high androgen levels, or frequent intermittent hypoxemia during sleep. The effect of heavy smoking cannot be evaluated. Further work on hematological adaptation to high altitude must pay special attention to sample characteristics. Copyright © 1990 Wiley-Liss, Inc., A Wiley Company.

[Effects of a lipid-based nutrient supplement on hemoglobin levels and anthropometric indicators in children from five districts in Huánuco Peru].

PubMed

Vargas-Vásquez, Alejandro; Bado, Ricardo; Alcázar, Lorena; Aquino, Oscar; Rodríguez, Amelia; Novalbos, José Pedro

2015-01-01

Objectives . To determine the effect of consumption of a lipid-based nutrient supplement (LNS) on hemoglobin levels, anemia and anthropometric indicators in children aged six to eleven months old in five districts in the province of Ambo in the region of Huanuco, Peru. A pre-experimental, pre-post study was performed. The study population included children aged six to eleven months old in 19 health facilities in five districts with very high vulnerability to chronic malnutrition in the province of Ambo, Huanuco. Data from 147 children who received the lipid-based nutrient supplement (LNS) from six to eleven months old were obtained. The mean hemoglobin significantly increased by 0.67 g/dL (p<0.05), the proportion of anemia dropped by 27 percentage points (p<0.001) and the mean z score for height/age decreased by 0.12 (p<0.05). No significant differences for z scores of weight/age and weight/height at the end of the study were found. The LNS had an adherence greater than 90%, and less than 10% of children in the study reported discomfort during consumption. LNS supplementation achieved improved hemoglobin levels and reduced the prevalence of anemia in children under twelve months, which might constitute an effective alternative to prevent and control childhood anemia.

Immunohistochemical detection of osteopontin in advanced head-and-neck cancer: prognostic role and correlation with oxygen electrode measurements, hypoxia-inducible-factor-1alpha-related markers, and hemoglobin levels.

PubMed

Bache, Matthias; Reddemann, Rolf; Said, Harun M; Holzhausen, Hans-Jürgen; Taubert, Helge; Becker, Axel; Kuhnt, Thomas; Hänsgen, Gabriele; Dunst, Jürgen; Vordermark, Dirk

2006-12-01

The tumor-associated glycoprotein osteopontin (OPN) is discussed as a plasma marker of tumor hypoxia. However, the association of immunohistochemical OPN expression in tumor sections with tumor oxygenation parameters (HF5, median pO(2)), the hypoxia-related markers hypoxia-inducible factor-1alpha (HIF-1alpha) and carbonic anhydrase IX (CAIX), or hemoglobin and systemic vascular endothelial growth factor (VEGF) levels has not been investigated. Tumor tissue sections of 34 patients with advanced head-and-neck cancer treated with radiotherapy were assessed by immunochemistry for the expression of OPN, HIF-1alpha, and CA IX. Relationship of OPN expression with tumor oxygenation parameters (HF5, median pO(2)), HIF-1alpha and CA IX expression, hemoglobin and serum VEGF level, and clinical parameters was studied. Bivariate analysis showed a significant correlation of positive OPN staining with low hemoglobin level (p = 0.02), high HIF-1alpha expression (p = 0.02), and high serum vascular endothelial growth factor level (p = 0.02) for advanced head-and-neck cancer. Furthermore, considering the 31 Stage IV patients, the median pO(2) correlated significantly with the OPN expression (p = 0.02). OPN expression alone had only a small impact on prognosis. However, in a univariate Cox proportional hazard regression model, the expression of either OPN or HIF-1alpha or CA IX was associated with a 4.1-fold increased risk of death (p = 0.02) compared with negativity of all three markers. Osteopontin expression detected immunohistochemically is associated with oxygenation parameters in advanced head-and-neck cancer. When the results of OPN, HIF-1alpha, and CA IX immunohistochemistry are combined into a hypoxic profile, a strong and statistically significant impact on overall survival is found.

Immunohistochemical detection of osteopontin in advanced head-and-neck cancer: Prognostic role and correlation with oxygen electrode measurements, hypoxia-inducible-factor-1{alpha}-related markers, and hemoglobin levels

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bache, Matthias; Reddemann, Rolf; Institute of Pathology, Martin-Luther-University Halle-Wittenberg, Halle

2006-12-01

Purpose: The tumor-associated glycoprotein osteopontin (OPN) is discussed as a plasma marker of tumor hypoxia. However, the association of immunohistochemical OPN expression in tumor sections with tumor oxygenation parameters (HF5, median pO{sub 2}), the hypoxia-related markers hypoxia-inducible factor-1{alpha} (HIF-1{alpha}) and carbonic anhydrase IX (CAIX), or hemoglobin and systemic vascular endothelial growth factor (VEGF) levels has not been investigated. Methods and Materials: Tumor tissue sections of 34 patients with advanced head-and-neck cancer treated with radiotherapy were assessed by immunochemistry for the expression of OPN, HIF-1{alpha}, and CA IX. Relationship of OPN expression with tumor oxygenation parameters (HF5, median pO{sub 2}), HIF-1{alpha}more » and CA IX expression, hemoglobin and serum VEGF level, and clinical parameters was studied. Results: Bivariate analysis showed a significant correlation of positive OPN staining with low hemoglobin level (p = 0.02), high HIF-1{alpha} expression (p = 0.02), and high serum vascular endothelial growth factor level (p = 0.02) for advanced head-and-neck cancer. Furthermore, considering the 31 Stage IV patients, the median pO{sub 2} correlated significantly with the OPN expression (p = 0.02). OPN expression alone had only a small impact on prognosis. However, in a univariate Cox proportional hazard regression model, the expression of either OPN or HIF-1{alpha} or CA IX was associated with a 4.1-fold increased risk of death (p = 0.02) compared with negativity of all three markers. Conclusion: Osteopontin expression detected immunohistochemically is associated with oxygenation parameters in advanced head-and-neck cancer. When the results of OPN, HIF-1{alpha}, and CA IX immunohistochemistry are combined into a hypoxic profile, a strong and statistically significant impact on overall survival is found.« less

Noninvasive investigation of skin local hypothermia influence upon local oxygenation and hemoglobin concentration

NASA Astrophysics Data System (ADS)

Douplik, Alexandre Y.; Kessler, Manfred D.; Kakihana, Yasuyuki; Krug, Alfons

1997-08-01

Functional evaluation of local hemoglobin concentration and hemoglobin oxygenation based on back scattering spectra from human skin in vivo have been obtained in visible range (502 - 628 nm) by a rapid microlightguide spectrometer (EMPHO II) with step 250 micrometer. Analysis of received results has shown that during local cooling there is two nearly simultaneous reactions: reduction of hemoglobin concentration and increase of hemoglobin oxygenation level. In a case when one has used previous heating of planning place for cooling, reduction of hemoglobin concentration is expressed higher by 22 - 33%.

Anemia prevalence and hemoglobin levels are associated with long-term exposure to air pollution in an older population.

PubMed

Honda, Trenton; Pun, Vivian C; Manjourides, Justin; Suh, Helen

2017-04-01

Anemia, a highly prevalent disorder in elderly populations, is associated with numerous adverse health outcomes, including increased mortality, impaired functional status and cognitive disorders. Approximately two-thirds of anemia in American elderly is caused by chronic inflammation or is unexplained. A potential contributing factor may include air pollution exposures, which have been shown to increase systemic inflammation and affect erythropoiesis. Few studies, however, have investigated the associations of air pollution on hemoglobin levels and anemia. We used linear regression models and modified Poisson regression with robust error variance to examine the associations of particulate matter (PM 2.5 ) and nitrogen dioxide (NO 2 ) on hemoglobin concentrations and prevalence of anemia, respectively, among 4121 older Americans enrolled in the National Social Life, Health, and Aging Project. We estimated participant-specific exposures to PM 2.5 using spatio-temporal models, and to NO 2 using nearest measurements from Environmental Protection Agency's Air Quality System. Hemoglobin levels were measured for participants in each of two data collection waves from dried blood spots. Anemia was defined using World Health Organization hemoglobin-based criteria of <13 and <12g/dL for men and women, respectively. Models were adjusted for age, sex, smoking status, race, income, education, neighborhood socioeconomic status, region, urbanicity and medication use. Mediation by C-reactive protein (CRP), a marker of systemic inflammation, was also investigated. An inter-quartile range (IQR, 3.9μg/m 3 ) increase in the one-year moving average PM 2.5 was positively associated with anemia prevalence (prevalence ratio, or PR 1.33, 95% CI: 1.23, 1.45) and decreases in average hemoglobin of 0.81g/dL (p<0.001). Similarly, an IQR (9.6ppb) increase in NO 2 was associated with anemia prevalence (PR 1.43, 95% CI: 1.25, 1.63) and a decrease in average hemoglobin of 0.81g/dL (p<0.001). Strong dose-response relationships were identified for both pollutants. Mediation of the effect of PM 2.5 by CRP was also identified (p=0.007). Air pollution exposures were significantly associated with increased prevalence of anemia and decreased hemoglobin levels in a cohort of older Americans. If causal, these associations could indicate that chronic air pollution exposure is an important risk factor for anemia in older adults. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Anemia Prevalence and Hemoglobin Levels are Associated with Long-Term Exposure to Air Pollution in an Older Population

PubMed Central

Honda, Trenton; Pun, Vivian C.; Manjourides, Justin; Suh, Helen

2017-01-01

BACKGROUND Anemia, a highly prevalent disorder in elderly populations, is associated with numerous adverse health outcomes, including increased mortality, impaired functional status and cognitive disorders. Approximately two-thirds of anemia in American elderly is caused by chronic inflammation or is unexplained. A potential contributing factor may include air pollution exposures, which have been shown to increase systemic inflammation and affect erythropoiesis. Few studies, however, have investigated the associations of air pollution on hemoglobin levels and anemia. METHODS We used linear regression models and modified Poisson regression with robust error variance to examine the associations of particulate matter (PM2.5) and nitrogen dioxide (NO2) on hemoglobin concentrations and prevalence of anemia, respectively, among 4,121 older Americans enrolled in the National Social Life, Health, and Aging Project. We estimated participant-specific exposures to PM2.5 using spatio-temporal models, and to NO2 using nearest measurements from Environmental Protection Agency’s Air Quality System. Hemoglobin levels were measured for participants in each of two data collection waves from dried blood spots. Anemia was defined using World Health Organization hemoglobin-based criteria of <13 and <12 g/dL for men and women, respectively. Models were adjusted for age, sex, smoking status, race, income, education, neighborhood socioeconomic status, region, urbanicity and medication use. Mediation by C-reactive protein (CRP), a marker of systemic inflammation, was also investigated. RESULTS An inter-quartile range (IQR, 3.9 μg/m3) increase in the one-year moving average PM2.5 was positively associated with anemia prevalence (prevalence ratio, or PR 1.33, 95% CI: 1.23, 1.45) and decreases in average hemoglobin of 0.81 g/dL (p<0.001). Similarly, an IQR (9.6 ppb) increase in NO2 was associated with anemia prevalence (PR 1.43, 95% CI: 1.25, 1.63) and a decrease in average hemoglobin of 0.81 g/dL (p<0.001). Strong dose-response relationships were identified for both pollutants. Mediation of the effect of PM2.5 by CRP was also identified (P=0.007). CONCLUSIONS/INTERPRETATIONS Air pollution exposures were significantly associated with increased prevalence of anemia and decreased hemoglobin levels in a cohort of older Americans. If causal, these associations could indicate that chronic air pollution exposure is an important risk factor for anemia in older adults. PMID:28153527

Association of classical markers and establishment of the dyslipidemic sub-phenotype of sickle cell anemia.

PubMed

Aleluia, Milena Magalhães; da Guarda, Caroline Conceição; Santiago, Rayra Pereira; Fonseca, Teresa Cristina Cardoso; Neves, Fábia Idalina; de Souza, Regiana Quinto; Farias, Larissa Alves; Pimenta, Felipe Araújo; Fiuza, Luciana Magalhães; Pitanga, Thassila Nogueira; Ferreira, Júnia Raquel Dutra; Adorno, Elisângela Vitória; Cerqueira, Bruno Antônio Veloso; Gonçalves, Marilda de Souza

2017-04-11

Sickle cell anemia (SCA) patients exhibit sub-phenotypes associated to hemolysis and vaso-occlusion. The disease has a chronic inflammatory nature that has been also associated to alterations in the lipid profile. This study aims to analyze hematological and biochemical parameters to provide knowledge about the SCA sub-phenotypes previously described and suggest a dyslipidemic sub-phenotype. A cross-sectional study was conducted from 2013 to 2014, and 99 SCA patients in steady state were enrolled. We assessed correlations and associations with hematological and biochemical data and investigated the co-inheritance of -α 3.7Kb -thalassemia (-α 3.7Kb -thal). Correlation analyses were performed using Spearman and Pearson coefficient. The median of quantitative variables between two groups was compared using t-test and Mann-Whitney. P-values <0.05 were considered statistically significant. We found significant association of high lactate dehydrogenase levels with decreased red blood cell count and hematocrit as well as high levels of total and indirect bilirubin. SCA patients with low nitric oxide metabolites had high total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol and reduced very low-density cholesterol, triglycerides, direct bilirubin level and reticulocyte counts. In SCA patients with high-density lipoprotein cholesterol greater than 40 mg/dL, we observed increased red blood cell count, hemoglobin, hematocrit, and fetal hemoglobin and decreased nitric oxide metabolites levels. The presence of -α 3.7Kb -thal was associated with high red blood cell count and low mean corpuscular volume, mean corpuscular hemoglobin, platelet count and total and indirect bilirubin levels. Our results provide additional information about the association between biomarkers and co-inheritance of -α 3.7Kb -thal in SCA, and suggest the role of dyslipidemia and nitric oxide metabolites in the characterization of this sub-phenotype.

Mutation Screening of the Krüppel-like Factor 1 Gene in Individuals With Increased Fetal Hemoglobin Referred for Hemoglobinopathy Investigation in South of Iran.

PubMed

Hamid, Mohammad; Ershadi Oskouei, Sanaz; Shariati, Gholamreza; Babaei, Esmaeil; Galehdari, Hamid; Saberi, Alihossein; Sedaghat, Alireza

2018-04-01

Any mutation in the Krüppel-like factor 1 (KLF1) gene may interfere with its proper related function in the erythropoiesis process and lead to alterations in proper activation of its downstream protein through globin switching, which results in an increase in fetal hemoglobin (HbF). This study aimed to investigate whether KLF1 mutation can associate with high level of HbF in individuals with increased fetal hemoglobin referred for screening of hemoglobinopathies in south of Iran. The human KLF1 gene was amplified via the polymerase chain reaction procedure, and sequencing was used to determine any mutation in these patients. Moreover, XmnI polymorphisms in the position of -158 of γ-globin gene promoter were analyzed in all patients by polymerase chain reaction restriction fragment length polymorphism. Analysis of sequencing revealed a missense mutation in the KLF1 gene, p.Ser102Pro (c.304T>C), which was detectable in 10 of 23 cases with elevated HbF level. This mutation was only detected in individuals who had a HbF level between 3.1% and 25.6%. Statistical analysis showed that the frequency of C allele is significantly correlated with a high level of HbF (P<0.05). The allele frequency of positive result of XmnI polymorphism in individuals with increased HbF level was also significant, which showed an association with increased HbF level (P<0.05). To the best of our knowledge, this is the first report of p.Ser102Pro (c.304T>C) in the KLF1 gene in β-thalassemia patients with increased level of fetal hemoglobin. According to statistical results of p.Ser102Pro mutation and XmnI polymorphism, it has been strongly suggested that both polymorphisms have an association with increased HbF samples. These nucleotide changes alone may not be the only elements raising the level of HbF, and other regulatory and modifying factors also play a role in HbF production.

Association between serum ferritin and hemoglobin levels and bone health in Korean adolescents: A nationwide population-based study.

PubMed

Jung, Dong-Wook; Park, Joo-Hyun; Kim, Do-Hoon; Choi, Moonyoung; Kim, Shinhye; Kim, Hyonchong; Seul, Da-Eun; Park, Soo Gyeong; Jung, Jin-Hyung; Han, Kyungdo; Park, Young-Gyu

2017-12-01

It is important to identify risk factors for low bone mass at a young age. An influence of iron store on bone health in the general population has been reported but has not been studied in adolescents. This study aimed to investigate the relationship between hemoglobin and serum ferritin levels and bone mineral content (BMC) in South Korean adolescents.This study was based on data collected during the 2009to 2010 Korea National Health and Nutrition Examination Survey. We included 1321 participants aged 10 to 18 years. BMC was measured at the femur and lumbar spine using dual-energy x-ray absorptiometry, and hemoglobin and serum ferritin levels were examined.In boys, hemoglobin and serum ferritin levels were positively associated with BMC of the total femur and lumbar spine after adjusting for confounders, and hemoglobin levels significantly increased as BMC increased at all sites (P for trend = .001 for total femur, .01 for femur neck, and <.001 for lumbar spine). Likewise, serum ferritin levels showed increasing trends according to increasing BMC of the total femur and lumbar spine in boys (P for trend = .04 for total femur; and <.001 for lumbar spine). However, these associations were not observed in girls.This study suggests a positive relationship between serum ferritin and hemoglobin levels and BMC in South Korean adolescent boys. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

Purification of diverse hemoglobins by metal salt precipitation.

PubMed

Zimmerman, Devon; Dienes, Jack; Abdulmalik, Osheiza; Elmer, Jacob J

2016-09-01

Although donated blood is the preferred material for transfusion, its limited availability and stringent storage requirements have motivated the development of blood substitutes. The giant extracellular hemoglobin (aka erythrocruorin) of the earthworm Lumbricus terrestris (LtEc) has shown promise as a blood substitute, but an efficient purification method for LtEc must be developed to meet the potential large demand for blood substitutes. In this work, an optimized purification process that uses divalent and trivalent metal salts to selectively precipitate human, earthworm, and bloodworm hemoglobin (HbA, LtEc, and GdHb, respectively) from crude solutions was developed. Although several metal ions were able to selectively precipitate LtEc, Zn(2+) and Ni(2+) provided the lowest heme oxidation and highest overall yield of LtEc. In contrast, Zn(2+) was the only metal ion that completely precipitated HbA and GdHb. Polyacrylamide gel electrophoresis (PAGE) analysis shows that metal precipitation removes several impurities to provide highly pure hemoglobin samples. Heme oxidation levels were relatively low for Zn(2+)-purified HbA and LtEc (2.4±1.3% and 5.3±2.1%, respectively), but slightly higher for Ni(2+)-purified LtEc (8.4±1.2%). The oxygen affinity and cooperativity of the precipitated samples are also identical to samples purified with tangential flow filtration (TFF) alone, indicating the metal precipitation does not significantly affect the function of the hemoglobins. Overall, these results show that hemoglobins from several different species can be highly purified using a combination of metal (Zn(2+)) precipitation and tangential flow filtration. Copyright © 2015 Elsevier Inc. All rights reserved.

Comparison of the BioRad Variant and Primus Ultra2 high-pressure liquid chromatography (HPLC) instruments for the detection of variant hemoglobins.

PubMed

Gosselin, R C; Carlin, A C; Dwyre, D M

2011-04-01

Hemoglobin variants are a result of genetic changes resulting in abnormal or dys-synchronous hemoglobin chain production (thalassemia) or the generation of hemoglobin chain variants such as hemoglobin S. Automated high-pressure liquid chromatography (HPLC) systems have become the method of choice for the evaluation of patients suspected with hemoglobinopathies. In this study, we evaluated the performance of two HPLC methods used in the detection of common hemoglobin variants: Variant and Ultra2. There were 377 samples tested, 26% (99/377) with HbS, 8.5% (32/377) with HbC, 20.7% (78/377) with other hemoglobin variant or thalassemia, and 2.9% with increased hemoglobin A(1) c. The interpretations of each chromatograph were compared. There were no differences noted for hemoglobins A(0), S, or C. There were significant differences between HPLC methods for hemoglobins F, A(2), and A(1) c. However, there was good concordance between normal and abnormal interpretations (97.9% and 96.2%, respectively). Both Variant and Ultra2 HPLC methods were able to detect most common hemoglobin variants. There was better discrimination for fast hemoglobins, between hemoglobins E and A(2), and between hemoglobins S and F using the Ultra2 HPLC method. © 2010 Blackwell Publishing Ltd.

Effects of nutritional and psychological status of the patients with advanced stomach cancer on physical performance status.

PubMed

Tian, Jun; Chen, Zhen-chun; Hang, Li-Fang

2009-10-01

The aim of this study was to assess the associations between coping mode, nutritional status, and psychological status and performance status of the patients with advanced stomach cancer. An epidemiological survey was conducted among 233 patients with advanced stomach cancer in Fujian, China. In-person interviews were performed for the participants with respect to information of psychological status prior to chemotherapy, nutritional status during chemotherapy, and physical performance status after chemotherapy. Multivariate logistic regression analyses showed that the level of hemoglobin (HB), level of daily calorie intake, score of Depression Status Inventory (DSI), and score of confrontation subscale of Medical Coping Modes Questionnaire had a significant influence on performance status (P < 0.05). The relative risks (95% confidence interval) were 2.06 (1.12-3.79) for low level of hemoglobin versus normal level of hemoglobin, 1.16 (1.02-1.32) for low level of daily calorie intake versus normal level of daily calorie intake, 5.89 (2.00-17.31) for DSI score > or =40 versus DSI score <40, and 3.17 (1.73-5.78) for low score of confrontation versus high score of confrontation, respectively. Depression, low score of "Confrontation", low levels of HB, and low level of daily calorie intake may be the risk factors of poor performance status of the patients with advanced stomach cancer.

Decreased nitrite levels in erythrocytes of children with β-thalassemia/hemoglobin E.

PubMed

Suvachananonda, Thitiwat; Wankham, Amara; Srihirun, Sirada; Tanratana, Pansakorn; Unchern, Supeenun; Fucharoen, Suthat; Chuansumrit, Ampaiwan; Sirachainan, Nongnuch; Sibmooh, Nathawut

2013-09-01

Nitrite anion is bioactive nitric oxide (NO) species circulating in blood, and represents the NO bioavailability and endothelial function. In this study, we aimed to investigate the nitrite levels and the correlation with hemolysis and severity in β-thalassemia/hemoglobin E (β-thal/HbE). 38 Children (12.0±1.9 years of age) with a diagnosis of mild, moderate and severe β-thalassemia were enrolled in the study. The blood nitrite levels and potential plasma NO consumption were measured by the chemiluminescence method. The nitrite levels in whole blood and erythrocytes of the severe thalassemia subjects were lower than those of the control subjects. At day 7 after transfusion of packed erythrocytes, the nitrite levels in erythrocytes increased. The plasma hemoglobin and NO consumption increased in the severe thalassemia subjects. The nitrite levels in erythrocytes inversely correlated with plasma hemoglobin, lactate dehydrogenase activity, potential NO consumption, and lipid peroxidation. Our studies demonstrate the decreased NO bioavailability in thalassemia, which could result from endothelial dysfunction, the increased potential NO consumption in plasma by cell-free hemoglobin and oxidative stress. Copyright © 2013 Elsevier Inc. All rights reserved.

Protective effect of total flavonoids of seabuckthorn (Hippophae rhamnoides) in simulated high-altitude polycythemia in rats.

PubMed

Zhou, Ji-Yin; Zhou, Shi-Wen; Du, Xiao-Huang; Zeng, Sheng-Ya

2012-09-28

Seabuckthorn (Hippophae rhamnoides L.) has been used to treat high altitude diseases. The effects of five-week treatment with total flavonoids of seabuckthorn (35, 70, 140 mg/kg, ig) on cobalt chloride (5.5 mg/kg, ip)- and hypobaric chamber (simulating 5,000 m)-induced high-altitude polycythemia in rats were measured. Total flavonoids decreased red blood cell number, hemoglobin, hematocrit, mean corpuscular hemoglobin levels, span of red blood cell electrophoretic mobility, aggregation index of red blood cell, plasma viscosity, whole blood viscosity, and increased deformation index of red blood cell, erythropoietin level in serum. Total flavonoids increased pH, pO₂, Sp(O₂), pCO₂ levels in arterial blood, and increased Na⁺, HCO₃⁻, Cl⁻, but decreased K⁺ concentrations. Total flavonoids increased mean arterial pressure, left ventricular systolic pressure, end-diastolic pressure, maximal rate of rise and decrease, decreased heart rate and protected right ventricle morphology. Changes in hemodynamic, hematologic parameters, and erythropoietin content suggest that administration of total flavonoids from seabuckthorn may be useful in the prevention of high altitude polycythaemia in rats.

Genome-wide analysis of aberrantly expressed lncRNAs and miRNAs with associated co-expression and ceRNA networks in β-thalassemia and hereditary persistence of fetal hemoglobin.

PubMed

Lai, Ketong; Jia, Siyuan; Yu, Shanjuan; Luo, Jianming; He, Yunyan

2017-07-25

The implications of lncRNAs regarding fetal hemoglobin (HbF) induction in hemoglobin disorders remain poorly understood. In this study, microarray analysis was performed to profile lncRNAs, miRNAs and mRNAs in individuals with hereditary persistence of fetal hemoglobin (HPFH), β-thalassemia carriers with high HbF levels and healthy controls. The results show aberrant expression of 862 lncRNAs, 568 mRNAs and 63 miRNAs in the high-HbF group compared with the control group. Altered NR_001589, NR_120526, T315543, miR-486-3p, miR-19b-1-5p and miR-20a-3p expression was confirmed by quantitative reverse transcription-polymerase chain reaction, and Spearman correlation coefficients revealed significant positive correlations with HbF. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses showed the hematopoietic cell lineage and apoptosis to be most significantly dysregulated in HbF induction. We analyzed coding genes near the lncRNAs and constructed a coding-noncoding co-expression network. Based on the results, lncRNAs likely contribute to increased HbF levels by activating expression of HBE1 and hematopoietic cell lineage-inducible molecules and by inhibiting that of apoptosis-inducible molecules. Finally, through construction of a competing endogenous RNA network, we found that 6 lncRNAs could bind competitively with miR-486-3p, resulting in increased HbF levels. Taken together, our findings provide new insights into the mechanisms of HbF induction and potentially provide new targets for the treatment of β-thalassemia major.

Genome-wide analysis of aberrantly expressed lncRNAs and miRNAs with associated co-expression and ceRNA networks in β-thalassemia and hereditary persistence of fetal hemoglobin

PubMed Central

Yu, Shanjuan; Luo, Jianming; He, Yunyan

2017-01-01

The implications of lncRNAs regarding fetal hemoglobin (HbF) induction in hemoglobin disorders remain poorly understood. In this study, microarray analysis was performed to profile lncRNAs, miRNAs and mRNAs in individuals with hereditary persistence of fetal hemoglobin (HPFH), β-thalassemia carriers with high HbF levels and healthy controls. The results show aberrant expression of 862 lncRNAs, 568 mRNAs and 63 miRNAs in the high-HbF group compared with the control group. Altered NR_001589, NR_120526, T315543, miR-486-3p, miR-19b-1-5p and miR-20a-3p expression was confirmed by quantitative reverse transcription-polymerase chain reaction, and Spearman correlation coefficients revealed significant positive correlations with HbF. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses showed the hematopoietic cell lineage and apoptosis to be most significantly dysregulated in HbF induction. We analyzed coding genes near the lncRNAs and constructed a coding-noncoding co-expression network. Based on the results, lncRNAs likely contribute to increased HbF levels by activating expression of HBE1 and hematopoietic cell lineage-inducible molecules and by inhibiting that of apoptosis-inducible molecules. Finally, through construction of a competing endogenous RNA network, we found that 6 lncRNAs could bind competitively with miR-486-3p, resulting in increased HbF levels. Taken together, our findings provide new insights into the mechanisms of HbF induction and potentially provide new targets for the treatment of β-thalassemia major. PMID:28624809

The adaptation of the fetal red cells of newborn lambs to extrauterine life: the role of 2,3-diphosphoglycerate and and adult hemoglobin.

PubMed

Bard, H; Fouron, J C; Grothe, A M; Soukini, M A; Cornet, A

1976-10-01

The purpose of this study was to determine the interrelationship of the rise and fall of 2,3-diphosphoglycerate (DPG) with the increase in adult hemoglobin and the decrease in red cell oxygen hemoglobin affinity after birth in normal lambs. It was found that the mean maximum DPG level was 26.71 +/- 4.98 mol/g Hb at 7.5 +/- 1.1 days. At the same time the mean P50 and adult hemoglobin level was 27.0 +/- 1.4 mm Hg and 31.1 +/- 11.i%, respectively. In the individual lambs, the level of their maximum DPG correlated inversely with the amount of adult hemoglobin (r-0.77, P less than 0.05). Once the DPG began to decrease, there was an inverse correlation between the DPG and the adult hemoglobin present in the red cell (r = 0.68, P less than 0.001). It appeared that the rise in DPG postanatally is only a compensatory mechanism until an adequate amount of adult hemoglobin is present. This fact was borne out by the second part of the study in which exchange transfusions with adult red cells were performed on five newborn lambs during the first 24 hr after birth and aborted the rise in DPG.

Hemoglobin-derived porphyrins preserved in a Middle Eocene blood-engorged mosquito

PubMed Central

Greenwalt, Dale E.; Goreva, Yulia S.; Siljeström, Sandra M.; Rose, Tim; Harbach, Ralph E.

2013-01-01

Although hematophagy is found in ∼14,000 species of extant insects, the fossil record of blood-feeding insects is extremely poor and largely confined to specimens identified as hematophagic based on their taxonomic affinities with extant hematophagic insects; direct evidence of hematophagy is limited to four insect fossils in which trypanosomes and the malarial protozoan Plasmodium have been found. Here, we describe a blood-engorged mosquito from the Middle Eocene Kishenehn Formation in Montana. This unique specimen provided the opportunity to ask whether or not hemoglobin, or biomolecules derived from hemoglobin, were preserved in the fossilized blood meal. The abdomen of the fossil mosquito was shown to contain very high levels of iron, and mass spectrometry data provided a convincing identification of porphyrin molecules derived from the oxygen-carrying heme moiety of hemoglobin. These data confirm the existence of taphonomic conditions conducive to the preservation of biomolecules through deep time and support previous reports of the existence of heme-derived porphyrins in terrestrial fossils. PMID:24127577

Have You Given Blood Lately?

MedlinePlus

... physical assessment that includes measuring vital signs and hemoglobin levels donating the blood (This takes about 15 ... per applicable state law have a normal blood hemoglobin level be free of infections that can be ...

Survival of rats subjected to acute anemia at different levels of erythrocyte 2,3-diphosphoglycerate.

PubMed

Arturson, G; Westman, M

1975-12-01

An experimental procedure was worked out in which rats were subjected to an exchange of erythrocytes, followed by acute anemia by means of hemodilution. One group of rats received erythrocytes with a high concentration of 2,3-diphosphoglycerate (DPG), and the other group was given erythrocytes with a low DPG concentration. The survival rate was equal in the two groups. Irrespective of DPG concentration, the rats whose hemoglobin concentration reached the lowest level died. The rats that died were also more acidotic than the others. The results indicate that the hemoglobin concentration and the pH value were more important determinants for survival than the DPG concentrations.

The influence of demographic, physical, behavioral, and dietary factors on hemoglobin adduct levels of acrylamide and glycidamide in the general U.S. population.

PubMed

Duke, Tina J; Ruestow, Peter S; Marsh, Gary M

2018-03-24

This study aims to better understand the individual characteristics and dietary factors that affect the relationship between estimated consumption of acrylamide and measured acrylamide hemoglobin adduct levels (HbAA) and glycidamide hemoglobin adduct levels (HbGA). Acrylamide levels in individual food items, estimated by the U.S. Food and Drug Administration, were linked to data collected in the 2003-2004 National Health and Nutrition Examination Survey. Multivariable linear regression was used to evaluate the relationship between estimated consumption of acrylamide and HbAA. A significant association between acrylamide intake and HbAA was observed, after adjustment for gender, race/ethnicity, smoking status, age, and BMI (R 2 = 0.34). Across quartiles of acrylamide consumption, HbAA and HbGA levels increased monotonically. Among nonsmokers, an evaluation of three heavily consumed, high AA concentration foods showed a positive trend between the consumed amount of fried potatoes and HbAA in children, adolescents, and adults. A significant positive trend between the consumed amount of potato chips or coffee was indicated in adolescents, adults, and seniors. Consumption of some individual foods affects HbAA concentrations more strongly and in an age-dependent manner. Our results suggest that effective dietary guidelines for controlling acrylamide intake should be subpopulation specific.

Hematological changes in Eleginops maclovinus during an experimental Caligus rogercresseyi infestation.

PubMed

Peña-Rehbein, Patricio; Ruiz, Karin; Ortloff, Alexander; Pizarro, María Isabel; Navarrete, Carolina

2013-01-01

Eleginops maclovinus has been an important fishery resource in Chile since 1957. Caligus rogercresseyi is one of the most prevalent ectoparasite species found on E. maclovinus. Hematocrit, hemoglobin level, red blood cell count (RBC), white blood cell count (WBC), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC) and differential white blood cell count were determined before and after an experimental infestation with C. rogercresseyi. We found significant differences in the hemoglobin level, WBC, MCV, MCH, MCHC, hematocrit level and RBC between infested and uninfested fish. Furthermore correlations between number of C. rogercresseyi with hematocrit, MCHC, neutrophil, eosinophil and lymphocyte counts were found. Hematological reference ranges of E. maclovinus in captivity conditions were also established.

Schistosomiasis japonica and childhood nutritional status in northeastern Leyte, the Philippines: a randomized trial of praziquantel versus placebo.

PubMed

McGarvey, S T; Aligui, G; Graham, K K; Peters, P; Olds, G R; Olveda, R

1996-05-01

The hypothesis that infection with Schistosoma japonicum causes decreased nutritional status was studied in a randomized trial among 170 males and females, mean (SD) age 11.4 (3.5) years, residing in an endemic region of northeastern Leyte, Philippines. The S. japonicum-infected children were randomized to receive praziquantel or placebo and followed-up six months after randomization. Stature, weight, triceps, subscapular, and calf skinfold thicknesses and their sum, and hemoglobin level were measured at baseline and follow-up. Schistosoma japonicum eggs were detected in Kato-Katz stool smears and the intensity of infection was assessed by quantitative egg count. Intensities of hookworm, ascaris, and trichuris infections were also measured. The six-month levels of the anthropometric measures and hemoglobin were adjusted for age and their baseline levels and then compared between the praziquantel and placebo groups. Treatment interactions were also analyzed by sex. Baseline anthropometric and hemoglobin levels and parasite infection intensities were the same in the two groups. At six months, the praziquantel group had significantly higher hemoglobin levels (P < 0.001) and sum of skinfolds (P < 0.001) than the placebo group. Males had a significantly greater increase in hemoglobin levels with treatment than did females. The hemoglobin increase was not due to changes in hookworm intensity. The results show that schistosomiasis japonica caused decreased nutritional status in children and probably is partly responsible for the malnutrition and reduction in growth for age described in prior cross-sectional studies.

Direct Measurement of Equilibrium Constants for High-Affinity Hemoglobins

PubMed Central

Kundu, Suman; Premer, Scott A.; Hoy, Julie A.; Trent, James T.; Hargrove, Mark S.

2003-01-01

The biological functions of heme proteins are linked to their rate and affinity constants for ligand binding. Kinetic experiments are commonly used to measure equilibrium constants for traditional hemoglobins comprised of pentacoordinate ligand binding sites and simple bimolecular reaction schemes. However, kinetic methods do not always yield reliable equilibrium constants with more complex hemoglobins for which reaction mechanisms are not clearly understood. Furthermore, even where reaction mechanisms are clearly understood, it is very difficult to directly measure equilibrium constants for oxygen and carbon monoxide binding to high-affinity (KD ≪ 1 μM) hemoglobins. This work presents a method for direct measurement of equilibrium constants for high-affinity hemoglobins that utilizes a competition for ligands between the "target" protein and an array of "scavenger" hemoglobins with known affinities. This method is described for oxygen and carbon monoxide binding to two hexacoordinate hemoglobins: rice nonsymbiotic hemoglobin and Synechocystis hemoglobin. Our results demonstrate that although these proteins have different mechanisms for ligand binding, their affinities for oxygen and carbon monoxide are similar. Their large affinity constants for oxygen, 285 and ∼100 μM−1 respectively, indicate that they are not capable of facilitating oxygen transport. PMID:12770899

Development and validation of a noncontact spectroscopic device for hemoglobin estimation at point-of-care

NASA Astrophysics Data System (ADS)

Sarkar, Probir Kumar; Pal, Sanchari; Polley, Nabarun; Aich, Rajarshi; Adhikari, Aniruddha; Halder, Animesh; Chakrabarti, Subhananda; Chakrabarti, Prantar; Pal, Samir Kumar

2017-05-01

Anemia severely and adversely affects human health and socioeconomic development. Measuring hemoglobin with the minimal involvement of human and financial resources has always been challenging. We describe a translational spectroscopic technique for noncontact hemoglobin measurement at low-resource point-of-care settings in human subjects, independent of their skin color, age, and sex, by measuring the optical spectrum of the blood flowing in the vascular bed of the bulbar conjunctiva. We developed software on the LabVIEW platform for automatic data acquisition and interpretation by nonexperts. The device is calibrated by comparing the differential absorbance of light of wavelength 576 and 600 nm with the clinical hemoglobin level of the subject. Our proposed method is consistent with the results obtained using the current gold standard, the automated hematology analyzer. The proposed noncontact optical device for hemoglobin estimation is highly efficient, inexpensive, feasible, and extremely useful in low-resource point-of-care settings. The device output correlates with the different degrees of anemia with absolute and trending accuracy similar to those of widely used invasive methods. Moreover, the device can instantaneously transmit the generated report to a medical expert through e-mail, text messaging, or mobile apps.

Does Racial/Ethnic Identity Influence the Effectiveness of a Community Health Worker Intervention for African American and Latino Adults With Type 2 Diabetes?

PubMed

Murayama, Hiroshi; Spencer, Michael S; Sinco, Brandy R; Palmisano, Gloria; Kieffer, Edith C

2017-06-01

Community health worker (CHW) interventions are known to be an effective strategy to improve health behaviors and outcomes in relation to diabetes, particularly for racial/ethnic communities. Although understanding the function of identity with same race/ethnicity among clients of CHW interventions could contribute to more effective program design, few studies have explored whether levels of racial/ethnic identity among participants can influence the effectiveness of CHW interventions. We tested the relationship between level of racial/ethnic identity and changes in hemoglobin A1c and diabetes self-efficacy among low-income African American and Latino adults with type 2 diabetes who participated in a CHW intervention. Data came from a randomized controlled trial of the CHW intervention with a 6-month delayed control group design for 164 African American and Latino adults in Detroit, Michigan. Racial/ethnic identity was created from two items and classified into high, moderate, and low. We combined the two arms (immediate and delayed) into one because there was no significant difference in baseline characteristics, other than age and postintervention self-efficacy, and multivariable linear regression models were applied in the analysis. Possession of high racial/ethnic identity was associated with greater improvement both in hemoglobin A1c and diabetes self-efficacy at 6 months. Moreover, among those with high hemoglobin A1c at preintervention, higher racial/ethnic identity had a greater impact on hemoglobin A1c improvement, compared with those with lower identity. This study suggests the importance of considering racial/ethnic identity of the participants in designing and operating the CHW intervention for racial/ethnic minority population.

Beneficial Effects of ragi (Finger Millet) on Hematological Parameters, Body Mass Index, and Scholastic Performance among Anemic Adolescent High-School Girls (AHSG).

PubMed

Karkada, Suja; Upadhya, Sharmila; Upadhya, Subramanya; Bhat, Gopalakrishna

2018-03-29

Adolescence is a period characterized by rapid physical, emotional, and mental growth and changes potentially resulting in health challenges. Anemia, which is a fairly common complication in this age group, is reported to negatively affect the cognitive ability of adolescents. Traditionally, ragi (Finger millet: Eleusine coracana), a cereal available in India, has been recommended as nutritional supplement to combat anemia because of its high protein and mineral content as well as anti-microbial property. This study sought to establish the effect of ragi in improving hematological parameters, body mass index, and scholastic performance among adolescent school girls. Sixty adolescent girls were randomly selected and divided into intervention (n = 30) and control groups (n = 30). The effect of dietary supplementation of ragi porridge on hematological parameters was evaluated on the intervention group at 45 and 90 days. Both groups were monitored for changes in body mass index and scholastic performance. A statistically significant increase in hemoglobin levels was observed in the intervention group after 90 days (from a mean of 11.3 g% to 12.54 g%; t (29)  = 7.514, p < .0001), with no significant changes in the control group. No statistically significant differences between the two groups were observed for mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, mean corpuscular volume, red cell distribution width, body mass index, and scholastic performance. The data show that daily dietary supplementation with ragi porridge has a positive effect on hemoglobin levels in adolescent high schools girls. A well planned nutrition education with dietary supplementation is thus recommended for better outcomes.

[Arginase Level in Suspended Red Blood Cells Storaged for Different Time].

PubMed

Fan, Li-Ping; Huang, Hao-Bo; Wei, Shi-Jin; Fu, Dan-Hui; Zeng, Feng; Huang, Qing-Hua; Hong, Jin-Quan

2015-10-01

To explore the effect of storage time on arginase level, and the possible source of arginase in suspended red blood cells (RBC). The arginase and myeloperoxidase (MPO) levels in suspended RBC and control plasma were detected by ELISA. The free hemoglobin level in suspended RBC and control plasma were detected by colorimetric method. The relationship between arginase level, MPO level and free hemoglobin level in suspended RBC was analyzed by the related methods. The arginase and free hemoglobin levels in suspended RBC were higher than those in control plasma. Otherwise, MPO level was not significantly different between suspended RBC and control plasma. All of them did not increase along with prolonging of storage time. There was not a significant correlation between arginase level and free hemoglobin level in suspended RBC of different storage time (r = 0.03), but arginase level positively correlated with MPO level in the suspended RBC of different storage time (r = 0.76). The arginase level in suspended RBC storaged for different time increases significantly, but not along with prolonging of storage time. The main possible source of arginase in the suspended RBC is the residual white blood cell, especially neutrophils.

Serum selenium concentrations and diabetes in U.S. adults: National Health and Nutrition Examination Survey (NHANES) 2003-2004

USDA-ARS?s Scientific Manuscript database

BACKGROUND: Increasing evidence suggests that high selenium levels are associated with diabetes and other cardiometabolic risk factors. OBJECTIVES: We evaluated the association of serum selenium concentrations with fasting plasma glucose, glycosylated hemoglobin levels, and diabetes in the most rec...

Methemoglobinemia and ascorbate deficiency in hemoglobin E β thalassemia: metabolic and clinical implications

PubMed Central

Allen, Angela; Fisher, Christopher; Premawardhena, Anuja; Bandara, Dayananda; Perera, Ashok; Allen, Stephen; St Pierre, Timothy; Olivieri, Nancy

2012-01-01

During investigations of the phenotypic diversity of hemoglobin (Hb) E β thalassemia, a patient was encountered with persistently high levels of methemoglobin associated with a left-shift in the oxygen dissociation curve, profound ascorbate deficiency, and clinical features of scurvy; these abnormalities were corrected by treatment with vitamin C. Studies of erythropoietin production before and after treatment suggested that, as in an ascorbate-deficient murine model, the human hypoxia induction factor pathway is not totally dependent on ascorbate levels. A follow-up study of 45 patients with HbE β thalassemia showed that methemoglobin levels were significantly increased and that there was also a significant reduction in plasma ascorbate levels. Haptoglobin levels were significantly reduced, and the high frequency of the 2.2 haptoglobin genotype may place an additional pressure on ascorbate as a free-radical scavenger in this population. There was, in addition, a highly significant correlation between methemoglobin levels, splenectomy, and factors that modify the degree of globin-chain imbalance. Because methemoglobin levels are modified by several mechanisms and may play a role in both adaptation to anemia and vascular damage, there is a strong case for its further study in other forms of thalassemia and sickle-cell anemia, particularly when splenic function is defective. PMID:22885163

Evaluation of four rapid methods for hemoglobin screening of whole blood donors in mobile collection settings.

PubMed

Gómez-Simón, Antonia; Navarro-Núñez, Leyre; Pérez-Ceballos, Elena; Lozano, María L; Candela, María J; Cascales, Almudena; Martínez, Constantino; Corral, Javier; Vicente, Vicente; Rivera, José

2007-06-01

Predonation hemoglobin measurement is a problematic requirement in mobile donation settings, where accurate determination of venous hemoglobin by hematology analyzers is not available. We have evaluated hemoglobin screening in prospective donors by the semiquantitative copper sulphate test and by capillary blood samples analyzed by three portable photometers, HemoCue, STAT-Site MHgb, and the CompoLab HB system. Capillary blood samples were obtained from 380 donors and tested by the copper sulphate test and by at least one of the named portable photometers. Predonation venous hemoglobin was also determined in all donors using a Coulter Max-M analyzer. The three photometers provided acceptable reproducibility (CV below 5%), and displayed a significant correlation between the capillary blood samples and the venous hemoglobin (R2 0.5-0.8). HemoCue showed the best agreement with venous hemoglobin determination, followed by STAT-Site MHgb, and the CompoLab HB system. The copper sulphate test provided the highest rate of donors acceptance (83%) despite unacceptable hemoglobin levels, and the lowest rate for donor deferral (1%) despite acceptable hemoglobin levels. The percentage of donors correctly categorized for blood donation by the portable hemoglobinometers was 85%, 82%, and 76% for CompoLab HB system, HemoCue and STAT-Site, respectively. Our data suggest that hemoglobin determination remains a conflictive issue in donor selection in the mobile setting. Without appropriate performance control, capillary hemoglobin screening by either the copper sulphate method or by the novel portable hemoglobinometers could be inaccurate, thus potentially affecting both donor safety and the blood supply.

The analysis of blood lead levels changeability over the 5-year observation in workers occupationally exposed to lead.

PubMed

Dobrakowski, Michał; Boroń, Marta; Kasperczyk, Sławomir; Kozłowska, Agnieszka; Kasperczyk, Aleksandra; Płachetka, Anna; Pawlas, Natalia

2017-06-01

The aim of the present study was to compare a group of workers with stable lead levels with a group of workers with fluctuating lead levels in terms of selected hematological, biochemical, and immunological parameters. The examined group included male workers occupationally exposed to lead. Blood lead (PbB) levels were measured every 3 months during the 5-year observation. Based on standard deviation of mean PbB levels, the examined population was divided into two groups: low level of fluctuation (L-SD) and high level of fluctuation (H-SD) groups. The mean and maximal PbB levels were significantly higher in the H-SD group than in the L-SD group by 9 and 22%, respectively. At the same time, the maximal level of zinc protoporphyrin (ZPP) and standard deviation of mean ZPP level were higher in the H-SD group by 29 and 55%, respectively. The maximal level of hemoglobin and white blood cell (WBC) count as well as standard deviation of the mean hemoglobin level and WBC count were higher in the H-SD group by 2, 8, 58, and 24%, respectively. The expression of nuclear factor kappa-B1 gene and telomerase reverse transcriptase gene was significantly greater in the H-SD group than in the L-SD group by 11 and 28%, respectively. Workers occupationally exposed to lead do not represent a homogenous population. Some present stable lead levels, whereas others have fluctuating lead levels. These fluctuations are related to secondary changes in ZPP and hemoglobin levels as well as WBC count.

Novel Visualization of Large Health Related Data Sets

DTIC Science & Technology

2015-03-01

Health Record Data: A Systematic Review B: McPeek Hinz E, Borland D, Shah H, West V, Hammond WE. Temporal Visualization of Diabetes Mellitus via Hemoglobin ...H, Borland D, McPeek Hinz E, West V, Hammond WE. Demonstration of Temporal Visualization of Diabetes Mellitus via Hemoglobin A1C Levels E... Hemoglobin A1c Levels and MultivariateVisualization of System-Wide National Health Service Data Using Radial Coordinates. (Copies in Appendix) 4.3

[Hemoglobin levels in pregnant women seen in health care centers of the Peruvian Ministry of Health, 2011].

PubMed

Munares-García, Oscar; Gómez-Guizado, Guillermo; Barboza-Del Carpio, Juan; Sánchez-Abanto, José

2012-01-01

Determine hemoglobin levels and prevalence of anemia in pregnant women seen in health care centers of the Ministry of Health at national level. Cross-cut study where the database of the Information System on the Nutritional Health of Children under 5 and Pregnant Women (SIEN) were analyzed. 287 691 records of pregnant women examined at the health care centers of the Peruvian Ministry of Health in 2011 were included, hemoglobin levels corrected by height, age, gestational age, altitude and prevalence of anemia (light, moderate and serious) were analyzed. Descriptive statistics and the chi-square method were used. Nationwide prevalence of anemia in pregnant women was 28.0%, with mild anemia being at 25.1%, moderate anemia at 2.6% and severe anemia at 0.2%. Hemoglobin levels are higher in older and younger women during the first months of pregnancy, prevalence of anemia decreases with altitude. Furthermore, prevalence is higher in the Highland regions. Huancavelica was the region with higher prevalence of anemia (53.6%), followed by Puno with 51.0%. Hemoglobin levels get higher as the mother gets older, and they go down in keeping with the gestation trimester and altitude. Huancavelica has the highest prevalence of anemia in pregnant women.

The effect of Iron Supplying on VO2 MAX and Haematology Parameter on Menstrual Woman

NASA Astrophysics Data System (ADS)

Nailuvar Sinaga, Rika; Sari Harahap, Novita; Mediyana Sari, Rima

2018-03-01

One of the supporting factors to have good aerobic endurance requires high VO2 max levels supported by good quality and quantity level of Haematology parameter especially such as erythrocytes, hematocrit and hemoglobin. One of the components in hemoglobin is iron which functions as theoxygen transport to parts of all body required in the process of metabolism. The objective of this research was to find out the difference between VO2 Max and Haematology parameter between iron supplying and no iron supplyingonmenstrual woman. The type of this research is quasi experimental research with non-randomized control group Pretest-Postest Design. The subjectsarethe studentsat faculty of Sports Sciences, Medan State University with the criteria of female gender, monthly regular menstrual cycle, having the level of health and the level of training, willing to be a sample by filling out informed consent. The total number of research subjectsis twenty students, divided into two groups namely the treatment group and the control group. The hematology parameter was measuredby Haemotology analyzer and VO2 Max was measured by multi-stage run. The result showed that there was a significant effect of iron supplyingon the increase of erythrocyte level on menstrual women, hemotocrit, haemoglobin and an increase in VO2 Max. Iron supplying on menstrual woman has the effect on the increase of erythrocyte, hematocrit, hemoglobin level and VO2 Max

Effects of Iron Supplementation and Activity on Serum Iron Depletion and Hemoglobin Levels in Female Athletes

ERIC Educational Resources Information Center

Cooter, G. Rankin; Mowbray, Kathy W.

1978-01-01

Research revealed that a four-month basketball training program did not significantly alter serum iron, total iron binding capacity, hemoglobin, and percent saturation levels in female basketball athletes. (JD)

Inhaled nitric oxide augments nitric oxide transport on sickle cell hemoglobin without affecting oxygen affinity.

PubMed

Gladwin, M T; Schechter, A N; Shelhamer, J H; Pannell, L K; Conway, D A; Hrinczenko, B W; Nichols, J S; Pease-Fye, M E; Noguchi, C T; Rodgers, G P; Ognibene, F P

1999-10-01

Nitric oxide (NO) inhalation has been reported to increase the oxygen affinity of sickle cell erythrocytes. Also, proposed allosteric mechanisms for hemoglobin, based on S-nitrosation of beta-chain cysteine 93, raise the possibility of altering the pathophysiology of sickle cell disease by inhibiting polymerization or by increasing NO delivery to the tissue. We studied the effects of a 2-hour treatment, using varying concentrations of inhaled NO. Oxygen affinity, as measured by P(50), did not respond to inhaled NO, either in controls or in individuals with sickle cell disease. At baseline, the arterial and venous levels of nitrosylated hemoglobin were not significantly different, but NO inhalation led to a dose-dependent increase in mean nitrosylated hemoglobin, and at the highest dosage, a significant arterial-venous difference emerged. The levels of nitrosylated hemoglobin are too low to affect overall hemoglobin oxygen affinity, but augmented NO transport to the microvasculature seems a promising strategy for improving microvascular perfusion.

The high affinity of small-molecule antioxidants for hemoglobin.

PubMed

Puscas, Cristina; Radu, Luana; Carrascoza, Francisco; Mot, Augustin C; Amariei, Diana; Lungu, Oana; Scurtu, Florina; Podea, Paula; Septelean, Raluca; Matei, Alina; Mic, Mihaela; Attia, Amr A; Silaghi-Dumitrescu, Radu

2018-06-18

Hemoglobin has previously been shown to display ascorbate peroxidase and urate peroxidase activity, with measurable Michaelis-Menten parameters that reveal a particularly low Km for ascorbate as well as for urate - lower than the respective in vivo concentrations of these antioxidants in blood. Also, direct detection of a hemoglobin-ascorbate interaction was possible by monitoring the 1H-NMR spectrum of ascorbate in the presence of hemoglobin. The relative difference in structures between ascorbate and urate may raise the question as to exactly what the defining structural features would be, for a substrate that binds to hemoglobin with high affinity. Reported here are Michaelis-Menten parameters for hemoglobin acting as peroxidase against a number of other substrates of varying structures - gallate, caffeate, rutin, 3-hydroxyflavone, 3,6-dihydroxyflavone, quercetin, epicatechin, luteolin - all with high affinities (some higher than those of physiologically-relevant redox partners of Hb - ascorbate and urate). Moreover, this high affinity appears general to animal hemoglobins. 1 H-NMR and 13 C-NMR spectra reveal a general pattern wherein small hydrophilic antioxidants appear to all have their signals affected, presumably due to binding to hemoglobin. Fluorescence and calorimetry measurements confirm these conclusions. Docking calculations confirm the existence of binding sites on hemoglobin and on myoglobin for ascorbate as well as for other antioxidants. Support is found for involvement of Tyr42 in binding of three out of the four substrates investigated in the case of hemoglobin (including ascorbate and urate, as blood-contained relevant substrates), but also for Tyr145 (with urate and caffeate) and Tyr35 (with gallate). Copyright © 2018 Elsevier Inc. All rights reserved.

A Mountain or a Plateau? Hematological Traits Vary Nonlinearly with Altitude in a Highland Lizard.

PubMed

González-Morales, Juan Carlos; Beamonte-Barrientos, Rene; Bastiaans, Elizabeth; Guevara-Fiore, Palestina; Quintana, Erendira; Fajardo, Victor

High-altitude organisms exhibit hematological adaptations to augment blood transport of oxygen. One common mechanism is through increased values of blood traits such as erythrocyte count, hematocrit, and hemoglobin concentration. However, a positive relationship between altitude and blood traits is not observed in all high-altitude systems. To understand how organisms adapt to high altitudes, it is important to document physiological patterns related to hypoxia gradients from a greater variety of species. Here, we present an extensive hematological description for three populations of Sceloporus grammicus living at 2,500, 3,400, and 4,300 m. We did not find a linear increase with altitude for any of the blood traits we measured. Instead, we found nonlinear relationships between altitude and the blood traits erythrocyte number, erythrocyte size, hematocrit, and hemoglobin concentration. Erythrocyte number and hematocrit leveled off as altitude increased, whereas hemoglobin concentration and erythrocyte size were highest at intermediate altitude. Additionally, lizards from our three study populations are similar in blood pH, serum electrolytes, glucose, and lactate. Given that the highest-altitude population did not show the highest levels of the variables we measured, we suggest these lizards may be using different adaptations to cope with hypoxia than lizards at low or intermediate altitudes. We discuss future directions that research could take to investigate such potential adaptations.

Asymptomatic Child Heterozygous for Hemoglobin S and Hemoglobin Pôrto Alegre

PubMed Central

Lojo, Liliana; Santiago-Borrero, Pedro; Rivera, Enid; Renta, Jessicca; Cadilla, Carmen L

2013-01-01

Hemoglobin Pôrto Alegre (PA) is a rare hemoglobin resulting from a mutation in β9(A6)Ser→Cys. We describe an asymptomatic Puerto Rican female with combined heterozygosity for Hb PA and Hb S. Since birth, she has maintained normal hemoglobin, bilirubin, LDH levels, and reticulocyte count. Peripheral smear evaluation has revealed normal erythrocyte morphology with no changes suggestive of hemolysis. We conclude that the presence of Hb PA does not increase the risk of red blood cell sickling in patients who carry the Hb S mutation. PMID:21225927

Epoetin alfa improves survival after chemoradiation for Stage III esophageal cancer: Final results of a prospective observational study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rades, Dirk; Tribius, Silke; Yekebas, Emre F.

Purpose: This prospective, nonrandomized study evaluates the effectiveness of epoetin alfa to maintain the hemoglobin levels at 12 to14 g/dL (optimal range for tumor oxygenation) during chemoradiation for Stage III esophageal cancer and its impact on overall survival (OS), metastatic-free survival (MFS), and locoregional control (LC). Methods and Materials: Ninety-six patients were included. Forty-two patients received epoetin alfa (150 IU/kg, 3 times a week) during radiotherapy, which was started at hemoglobin less than 13 g/dL and stopped at 14 g/dL or higher. Hemoglobin levels were measured weekly during RT. Results: Both groups were balanced for age, sex, performance status, tumormore » length/location, histology, grading, T-stage/N-stage, chemotherapy, treatment schedule, and hemoglobin before RT. Median change of hemoglobin was +0.3 g/dL/wk with epoetin alfa and -0.5 g/dL/wk without epoetin alfa. At least 60% of hemoglobin levels were 12 to 14 g/dL in 64% and 17% of the patients, respectively (p < 0.001). Patients who received epoetin alfa had better OS (32% vs. 8% at 2 years, p = 0.009) and LC (67% vs. 15% at 2 years, p = 0.001). MFS was not significantly different (42% vs. 18% at 2 years, p = 0.09). Conclusions: The findings suggest that epoetin alfa when used to maintain the hemoglobin levels at 12 to 14 g/dL can improve OS and LC of Stage III esophageal cancer patients.« less

Oxygen-modifying treatment with ARCON reduces the prognostic significance of hemoglobin in squamous cell carcinoma of the head and neck

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hoogsteen, Ilse J.; Pop, Lucas A.M.; Marres, Henri A.M.

2006-01-01

Purpose: To evaluate the prognostic significance of hemoglobin (Hb) levels measured before and during treatment with accelerated radiotherapy with carbogen and nicotinamide (ARCON). Methods and Materials: Two hundred fifteen patients with locally advanced tumors of the head and neck were included in a phase II trial of ARCON. This treatment regimen combines accelerated radiotherapy for reduction of repopulation with carbogen breathing and nicotinamide to reduce hypoxia. In these patients, Hb levels were measured before, during, and after radiotherapy. Results: Preirradiation and postirradiation Hb levels were available for 206 and 195 patients respectively. Hb levels below normal were most frequently seenmore » among patients with T4 (p < 0.001) and N2 (p < 0.01) disease. Patients with a larynx tumor had significantly higher Hb levels (p < 0.01) than other tumor sites. During radiotherapy, 69 patients experienced a decrease in Hb level. In a multivariate analysis there was no prognostic impact of Hb level on locoregional control, disease-free survival, and overall survival. Primary tumor site was independently prognostic for locoregional control (p = 0.018), and gender was the only prognostic factor for disease-free and overall survival (p < 0.05). High locoregional control rates were obtained for tumors of the larynx (77%) and oropharynx (72%). Conclusion: Hemoglobin level was not found to be of prognostic significance for outcome in patients with squamous cell carcinoma of the head and neck after oxygen-modifying treatment with ARCON.« less

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

PubMed

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 < 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 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 mean cellular volume, serum ferritin, and serum transferrin receptor were 76.6, 12.9, and 4.89 mg/L, respectively. Reticulocyte hemoglobin content had the largest area under the curve of 0.929, while those for mean cellular volume, serum ferritin, serum transferrin receptor were 0.922, 0.887, and 0.900, respectively. Reticulocyte hemoglobin content has a high sensitivity and specificity in the diagnosis of iron deficiency anemia, and its comprehensive diagnostic efficacy is better than other traditional indicators-such as serum ferritin and serum transferrin receptor.

Hemoglobin A1c Level Is Not Related to the Severity of Atherosclerosis in Patients with Acute Coronary Syndrome.

PubMed

Wang, Xinhong; Han, Zhenhua; Hao, Guanghua; Li, Yongqin; Dong, Xin; Wang, Congxia

2015-01-01

The relationship between hemoglobin A1c (HbA1c) levels and the extent of coronary artery stenosis in patients with acute coronary syndrome (ACS) remains uncertain. The present study aimed to assess the correlation of HbA1c level with angiographic coronary atherosclerosis. 292 consecutive ACS patients were enrolled and stratified into three groups according to HbA1c levels (group 1: < 6.0%, n = 137; group 2: 6.0-6.4%, n = 67; group 3: ≥ 6.5%, n = 88). The severity of coronary arteriosclerosis was assessed by Gensini score. The relationship between HbA1c and Gensini score was analyzed by multiple variables analysis. HbA1c level was not associated with the severity of CAD assessed by Gensini score in patients with ACS, even after the adjustment for other risk factors. However, NT-proBNP, ApoA1 and LVEF levels were independent predictors for CAD severity. Moreover, HbA1c level was not associated with the risk of high Gensini score (> 40) by logistic regression analysis. Diabetes mellitus (DM) and LVEF levels were two independent risk factors for high Gensini score. HbA1c level is not a significant and independent marker for the severity of angiography in ACS patients, even in high-risk patients.

Predictors of Hyporesponsiveness to Erythropoiesis-Stimulating Agents in Hemodialysis Patients

PubMed Central

Kalantar-Zadeh, Kamyar; Lee, Grace H; Miller, Jessica E.; Streja, Elani; Jing, Jennie; Robertson, John A; Kovesdy, Csaba P.

2009-01-01

Background Identification of predictors of hyporesponsiveness to erythropoietin-stimulating agents (ESA) in hemodialysis (HD) patients may help improve anemia management and reduce hemoglobin variability. Study Design We conducted repeated measure and logistic regression analyses in a retrospective cohort of long-term HD patients to examine the association of iron markers and measures of renal osteodystrophy with ESA-responsiveness. The ESA-response coefficient at the individual level, i.e., the least-confounded dose-response association, was separated from the population level, assumed to represent confounding by medical indication. Setting/Participants The national database of a large dialysis organization (DaVita) with 38,328 surviving prevalent HD patients over 12 months, who received ESA for at least 3 consecutive calendar quarters, was examined. Predictors Serum levels of ferritin, iron saturation ratio (ISAT), intact parathyroid hormone (PTH) and alkaline phosphatase levels. Outcomes/Other Measurements The main outcome was case-mix adjusted hemoglobin response to quarterly averaged ESA dose at individual level. The odds ratio (OR) of the greatest vs. poorest ESA-response quartile at patient level was calculated. OR<1.0 indicated ESA hyporesponsiveness and OR>1.0 enhanced responsiveness. Results The mean (±SD) ESA-response coefficients of the least to most responsive quartiles were 0.301±0.033, 0.344±0.004, 0.357±0.004, and 0.389±0.026 g/dL higher hemoglobin per 1,000 units/week higher ESA dose in each quarter, respectively. The ORs of the greatest vs. poorest ESA-responsiveness at patient level were the following: Serum ferritin<200 ng/ml: 0.77 [95% confidence interval: 0.70–0.86] (reference: 200–500 ng/ml), ISAT<20%: 0.54 [0.49–0.59] (reference: 20–30%), intact PTH≥600 pg/ml: 0.54 [0.49–0.60] (reference: 150–300 pg/ml), and alkaline phosphatase ≥160 IU/L: 0.64 [0.58–0.70] (reference: 80–120 IU/L). Lower estimated dietary protein intake and serum levels of nutritional markers were also associated with higher risk of ESA-hyporesponsiveness. Limitations Our results may incorporate uncontrolled confounding. Achieved hemoglobin may have different associations than targeted hemoglobin. Conclusions In long-term HD patients, low iron stores, hyperparathyroidism and high turnover bone disease are associated with significant ESA-hyporesponsiveness. Prospective studies are needed to verify these associations. PMID:19339087

Iron bioavailability of maize hemoglobin in a Caco-2 cell culture model

USDA-ARS?s Scientific Manuscript database

Maize is an important staple crop in many parts of the world but has low iron bioavailability, in part due to its high phytate content. Hemoglobin is a form of iron that is highly bioavailable and its bioavailability is not inhibited by phytate. We hypothesize that maize hemoglobin is a highly bioav...

Effects of lead and cadmium co-exposure on hemoglobin in a Chinese population.

PubMed

Chen, Xiao; Zhou, Hao; Li, Xiaoshuang; Wang, Zhongqiu; Zhu, Guoying; Jin, Taiyi

2015-03-01

Cadmium (Cd) and lead (Pb) show adverse effects on hemoglobin. But most studies are focussed on one single agent. In this study, we observed the main and interactive effects of Cd and Pb on the hemoglobin level in a Chinese population. A total of 308 persons (202 women and 106 men), living in controlled and polluted areas, were included in this study. Blood and urine were collected to determine the levels of hemoglobin (Hb), Cd, Pb, and urinary N-acetyl-β-D-glucosaminidase (UNAG). The Cd and Pb level of subjects living in the polluted area were significantly higher compared to those living in the control area (p<0.05). The level of hemoglobin was declined with the increasing BPb (p<0.05) and BCd in women. The Hb of women and men with the highest level of BCd and BPb were decreased by 8.3g/L and 10.7 g/L compared to those with the lowest level of BCd and BPb, respectively. The Hb level of those women and men with the highest level of UNAG decreased by 4.2g/L and 17.2g/L compared with those with low level of UNAG, respectively. Hb was negatively associated with BPb, BCd, and UNAG. This study evidenced that Cd and Pb can influence Hb level. In addition, our study shows that Cd and Pb may have interactive effects on Hb and Hb level was correlated with tubular dysfunction caused by Cd and Pb exposure. Copyright © 2015 Elsevier B.V. All rights reserved.

Blood levels of toxic metals and rare earth elements commonly found in e-waste may exert subtle effects on hemoglobin concentration in sub-Saharan immigrants.

PubMed

Henríquez-Hernández, Luis Alberto; Boada, Luis D; Carranza, Cristina; Pérez-Arellano, José Luis; González-Antuña, Ana; Camacho, María; Almeida-González, Maira; Zumbado, Manuel; Luzardo, Octavio P

2017-12-01

Pollution by heavy metals and more recently by rare earth elements (REE) and other minor elements (ME) has increased due in part to their high use in technological and electronic devices. This contamination can become very relevant in those sites where e-waste is improperly processed, as it is the case in many countries of the African continent. Exposure to some toxic elements has been associated to certain hematological disorders, specifically anemia. In this study, the concentrations of 48 elements (including REE and other ME) were determined by ICP-MS in whole blood samples of sub-Saharan immigrants with anemia (n=63) and without anemia (n=78). We found that the levels of Fe, Cr, Cu, Mn, Mo, and Se were significantly higher in the control group than in the anemia group, suggesting that anemia was mainly due to nutritional deficiencies. However, since other authors have suggested that in addition to nutritional deficiency, exposure to some elements may influence hemoglobin levels, we wanted to explore the role of a broad panel of toxic and "emerging" elements in hemoglobin deficiency. We found that the levels of Ag, As, Ba, Bi, Ce, Eu, Er, Ga, La, Nb, Nd, Pb, Pr, Sm, Sn, Ta, Th, Tl, U and V were higher in anemic participants than in controls. For most of these elements an inverse correlation with hemoglobin concentration was found. Some of them also correlated inversely with blood iron levels, pointing to the possibility that a higher rate of intestinal uptake of these could exist in relation to a nutritional deficiency of iron. However, the higher levels of Pb, and the group of REE and other ME in anemic participants were independent of iron levels, pointing to the possibility that these elements could play a role in the development of anemia. Copyright © 2017 Elsevier Ltd. All rights reserved.

Low affinity PEGylated hemoglobin from Trematomus bernacchii, a model for hemoglobin-based blood substitutes

PubMed Central

2011-01-01

Background Conjugation of human and animal hemoglobins with polyethylene glycol has been widely explored as a means to develop blood substitutes, a novel pharmaceutical class to be used in surgery or emergency medicine. However, PEGylation of human hemoglobin led to products with significantly different oxygen binding properties with respect to the unmodified tetramer and high NO dioxygenase reactivity, known causes of toxicity. These recent findings call for the biotechnological development of stable, low-affinity PEGylated hemoglobins with low NO dioxygenase reactivity. Results To investigate the effects of PEGylation on protein structure and function, we compared the PEGylation products of human hemoglobin and Trematomus bernacchii hemoglobin, a natural variant endowed with a remarkably low oxygen affinity and high tetramer stability. We show that extension arm facilitated PEGylation chemistry based on the reaction of T. bernacchii hemoglobin with 2-iminothiolane and maleimido-functionalyzed polyethylene glycol (MW 5000 Da) leads to a tetraPEGylated product, more homogeneous than the corresponding derivative of human hemoglobin. PEGylated T. bernacchii hemoglobin largely retains the low affinity of the unmodified tetramer, with a p50 50 times higher than PEGylated human hemoglobin. Moreover, it is still sensitive to protons and the allosteric effector ATP, indicating the retention of allosteric regulation. It is also 10-fold less reactive towards nitrogen monoxide than PEGylated human hemoglobin. Conclusions These results indicate that PEGylated hemoglobins, provided that a suitable starting hemoglobin variant is chosen, can cover a wide range of oxygen-binding properties, potentially meeting the functional requirements of blood substitutes in terms of oxygen affinity, tetramer stability and NO dioxygenase reactivity. PMID:22185675

Long-term effects of intensive glucose lowering on cardiovascular outcomes.

PubMed

Gerstein, Hertzel C; Miller, Michael E; Genuth, Saul; Ismail-Beigi, Faramarz; Buse, John B; Goff, David C; Probstfield, Jeffrey L; Cushman, William C; Ginsberg, Henry N; Bigger, J Thomas; Grimm, Richard H; Byington, Robert P; Rosenberg, Yves D; Friedewald, William T

2011-03-03

Intensive glucose lowering has previously been shown to increase mortality among persons with advanced type 2 diabetes and a high risk of cardiovascular disease. This report describes the 5-year outcomes of a mean of 3.7 years of intensive glucose lowering on mortality and key cardiovascular events. We randomly assigned participants with type 2 diabetes and cardiovascular disease or additional cardiovascular risk factors to receive intensive therapy (targeting a glycated hemoglobin level below 6.0%) or standard therapy (targeting a level of 7 to 7.9%). After termination of the intensive therapy, due to higher mortality in the intensive-therapy group, the target glycated hemoglobin level was 7 to 7.9% for all participants, who were followed until the planned end of the trial. Before the intensive therapy was terminated, the intensive-therapy group did not differ significantly from the standard-therapy group in the rate of the primary outcome (a composite of nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes) (P=0.13) but had more deaths from any cause (primarily cardiovascular) (hazard ratio, 1.21; 95% confidence interval [CI], 1.02 to 1.44) and fewer nonfatal myocardial infarctions (hazard ratio, 0.79; 95% CI, 0.66 to 0.95). These trends persisted during the entire follow-up period (hazard ratio for death, 1.19; 95% CI, 1.03 to 1.38; and hazard ratio for nonfatal myocardial infarction, 0.82; 95% CI, 0.70 to 0.96). After the intensive intervention was terminated, the median glycated hemoglobin level in the intensive-therapy group rose from 6.4% to 7.2%, and the use of glucose-lowering medications and rates of severe hypoglycemia and other adverse events were similar in the two groups. As compared with standard therapy, the use of intensive therapy for 3.7 years to target a glycated hemoglobin level below 6% reduced 5-year nonfatal myocardial infarctions but increased 5-year mortality. Such a strategy cannot be recommended for high-risk patients with advanced type 2 diabetes. (Funded by the National Heart, Lung and Blood Institute; ClinicalTrials.gov number, NCT00000620.).

Three-state combinatorial switch models as applied to the binding of oxygen by human hemoglobin.

PubMed

Straume, M; Johnson, M L

1988-02-23

We have generated a series of all 6561 unique, discrete three-state combinatorial switch models to describe the partitioning of the cooperative oxygen-binding free change among the 10 variously ligated forms of human hemoglobin tetramers. These models were inspired by the experimental observation of Smith and Ackers that the cooperative free energy of the intersubunit contact regions of the 10 possible ligated forms of human hemoglobin tetramers can be represented by a particular distribution of three distinct energy levels [Smith, F. R., & Ackers, G. K. (1985) Proc. Natl. Acad. Sci. U.S.A. 82, 5347-5351]. A statistical thermodynamic formulation accounting for both dimer-tetramer equilibria and ligand binding properties of hemoglobin solutions as a function of oxygen and protein concentrations was utilized to exhaustively test these thermodynamic models. In this series of models each of the 10 ligated forms of the hemoglobin tetramer can exist in one, and only one, of three possible energy levels; i.e., each ligated form was assumed to be associated with a discrete energy state. This series of models includes all possible ways that the 10 ligation states of hemoglobin can be distributed into three distinct cooperative energy levels. The mathematical models, as presented here, do not permit equilibria between energy states to exist for any of the 10 unique ligated forms of hemoglobin tetramers. These models were analyzed by nonlinear least-squares estimation of the free energy parameters characteristic of this statistical thermodynamic development.(ABSTRACT TRUNCATED AT 250 WORDS)

Asymptomatic child heterozygous for hemoglobin S and hemoglobin Pôrto Alegre.

PubMed

Lojo, Liliana; Santiago-Borrero, Pedro; Rivera, Enid; Renta, Jessicca; Cadilla, Carmen L

2011-03-01

Hemoglobin Pôrto Alegre (PA) is a rare hemoglobin resulting from a mutation in β9(A6)Ser → Cys. We describe an asymptomatic Puerto Rican female with combined heterozygosity for Hb PA and Hb S. Since birth, she has maintained normal hemoglobin, bilirubin, LDH levels, and reticulocyte count. Peripheral smear evaluation has revealed normal erythrocyte morphology with no changes suggestive of hemolysis. We conclude that the presence of Hb PA does not increase the risk of red blood cell sickling in patients who carry the Hb S mutation. Copyright © 2010 Wiley-Liss, Inc.

Chromatographic measurements of hemoglobin A2 in blood samples that contain sickle hemoglobin.

PubMed

Shokrani, M; Terrell, F; Turner, E A; Aguinaga, M D

2000-04-01

In the sickle cell syndromes, Hb A2 measurements aid in the differential diagnosis of sickle cell anemia from sickle-beta-thalassemia. The purpose of this study is to assess the Hb A2 levels in samples containing sickle hemoglobin (Hb S) by the use of an automated high performance liquid chromatography system (HPLC-Variant beta-thalassemia Short Program). The blood samples analyzed were from individuals of African descent living in the state of Tennessee who had either sickle cell trait (Hb AS), sickle cell disease (Hb SS), or sickle cell-hemoglobin C disease (Hb SC). Interestingly, the Hb A2 levels determined by HPLC were found elevated in samples containing Hb S. The Hb A2 mean in Hb AS samples (n=146) is 4.09% (SD +/- 0.42, range 2.20 to 5.20%); in Hb SS samples (n=33) it is 3.90% (SD +/- 1.08, range 0.60 to 5.90%); and in Hb SC samples (n=27) it is 4.46% (SD +/- 0.70, range 2.30 to 5.91%). The Hb A2 mean by HPLC in normal individuals (Hb AA, n=70) is 2.57% (SD +/- 0.25, range 2.1 to 3.0%), and the Hb A2 range in beta-thalassemia carriers is 4 to 9%. Our results show that the Hb A2 levels in Hb S-containing samples partially overlap with those expected from beta-thalassemia carriers. The hemoglobinopathy laboratory should be aware of this apparent elevation in Hb A2 levels determined by HPLC in individuals carrying Hb S. Other factors, such as family history and clinical symptoms, should be taken into account before a diagnosis of sickle cell trait, sickle-beta-thalassemia, or sickle cell anemia is made.

Nutritional status and CD4 cell counts in patients with HIV/AIDS receiving antiretroviral therapy.

PubMed

Santos, Ana Célia Oliveira dos; Almeida, Ana Maria Rampeloti

2013-01-01

Even with current highly active antiretroviral therapy, individuals with AIDS continue to exhibit important nutritional deficits and reduced levels of albumin and hemoglobin, which may be directly related to their cluster of differentiation 4 (CD4) cell counts. The aim of this study was to characterize the nutritional status of individuals with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) and relate the findings to the albumin level, hemoglobin level and CD4 cell count. Patients over 20 years of age with AIDS who were hospitalized in a university hospital and were receiving antiretroviral therapy were studied with regard to clinical, anthropometric, biochemical and sociodemographic characteristics. Body mass index, percentage of weight loss, arm circumference, triceps skinfold and arm muscle circumference were analyzed. Data on albumin, hemoglobin, hematocrit and CD4 cell count were obtained from patient charts. Statistical analysis was performed using Fisher's exact test, Student's t-test for independent variables and the Mann-Whitney U-test. The level of significance was set to 0.05 (α = 5%). Statistical analysis was performed using Statistical Package for the Social Sciences (SPSS) 17.0 software for Windows. Of the 50 patients evaluated, 70% were male. The prevalence of malnutrition was higher when the definition was based on arm circumference and triceps skinfold measurement. The concentrations of all biochemical variables were significantly lower among patients with a body mass index of less than 18.5kg/m2. The CD4 cell count, albumin, hemoglobin and hematocrit anthropometric measures were directly related to each other. These findings underscore the importance of nutritional follow-up for underweight patients with AIDS, as nutritional status proved to be related to important biochemical alterations.

A genome-editing strategy to treat β-hemoglobinopathies that recapitulates a mutation associated with a benign genetic condition.

PubMed

Traxler, Elizabeth A; Yao, Yu; Wang, Yong-Dong; Woodard, Kaitly J; Kurita, Ryo; Nakamura, Yukio; Hughes, Jim R; Hardison, Ross C; Blobel, Gerd A; Li, Chunliang; Weiss, Mitchell J

2016-09-01

Disorders resulting from mutations in the hemoglobin subunit beta gene (HBB; which encodes β-globin), mainly sickle cell disease (SCD) and β-thalassemia, become symptomatic postnatally as fetal γ-globin expression from two paralogous genes, hemoglobin subunit gamma 1 (HBG1) and HBG2, decreases and adult β-globin expression increases, thereby shifting red blood cell (RBC) hemoglobin from the fetal (referred to as HbF or α2γ2) to adult (referred to as HbA or α2β2) form. These disorders are alleviated when postnatal expression of fetal γ-globin is maintained. For example, in hereditary persistence of fetal hemoglobin (HPFH), a benign genetic condition, mutations attenuate γ-globin-to-β-globin switching, causing high-level HbF expression throughout life. Co-inheritance of HPFH with β-thalassemia- or SCD-associated gene mutations alleviates their clinical manifestations. Here we performed CRISPR-Cas9-mediated genome editing of human blood progenitors to mutate a 13-nt sequence that is present in the promoters of the HBG1 and HBG2 genes, thereby recapitulating a naturally occurring HPFH-associated mutation. Edited progenitors produced RBCs with increased HbF levels that were sufficient to inhibit the pathological hypoxia-induced RBC morphology found in SCD. Our findings identify a potential DNA target for genome-editing-mediated therapy of β-hemoglobinopathies.

Racial Contrasts in Hemoglobin Levels and Dietary Patterns Related to Hematopoiesis in Children: The Bogalusa Heart Study.

ERIC Educational Resources Information Center

Nicklas, Theresa A.; And Others

1987-01-01

Racial differences in hemoglobin were explored in pre-adolescent and adolescent children. After controlling for variations in dietary patterns, race accounted for a notable proportion of hemoglobin variance in both age groups. These differences exist independently of nutrient intake and maturational changes. (Author/VM)

High exposure to zidovudine during the first 2 weeks of life and concentration-toxicity relationships.

PubMed

Hirt, Déborah; Warszawski, Josiane; Firtion, Ghislaine; Giraud, Carole; Chappuy, Hélène; Lechenadec, Jérôme; Benaboud, Sihem; Urien, Saïk; Blanche, Stéphane; Tréluyer, Jean-Marc

2013-08-15

The aims of the study were in a large group of neonates to identify the relative effect of bodyweight, postnatal age, and gestational age on zidovudine (ZDV) pharmacokinetics; to link concentrations with lactate and hemoglobin levels; and to find the more appropriate neonatal ZDV dose. In 484 neonates aged 3-30 days, born to HIV-infected mothers, 767 ZDV and 417 ZDV glucuronide concentrations were collected. Using a population approach, ZDV clearance per kilogram increased with postnatal age but not with gestational age. High neonatal exposures were found as follows: 14,025 ng/mL·h the first week and 6528 ng/mL·h the second week in comparison to 3000 ng/mL·h in adults. At month 1, median lactate level was 2.8 mmol/L (60%, ≥2.5 mmol/L) and median hemoglobin was 10.1 g/dL (90%, <12 g/dL). ZDV trough concentrations at first sampling (days 3-7) or at last sampling (day 20 ± 10) were significantly negatively correlated to hemoglobin at months 1, 3, and 6 (P < 0.02). ZDV maximal or trough concentrations at days 3-7 and at day 20 ± 10 were significantly positively correlated to lactate levels at months 3 and 6, respectively. To obtain an exposure comparable to adults, which should reduce neonatal toxicity, doses should to be decreased during the first 2 weeks of life.

Blood oxygen binding in hypoxaemic calves.

PubMed

Cambier, Carole; Clerbaux, Thierry; Detry, Bruno; Marville, Vincent; Frans, Albert; Gustin, Pascal

2002-01-01

Blood oxygen transport and tissue oxygenation were studied in 28 calves from the Belgian White and Blue breed (20 healthy and 8 hypoxaemic ones). Hypoxaemic calves were selected according to their high respiratory frequency and to their low partial oxygen pressure (PaO2) in the arterial blood. Venous and arterial blood samples were collected, and 2,3-diphosphoglycerate, adenosine triphosphate, chloride, inorganic phosphate and hemoglobin concentrations, and pH, PCO, and PO2 were determined. An oxygen equilibrium curve (OEC) was measured in standard conditions, for each animal. The arterial and venous OEC were calculated, taking body temperature, pH and PCO2 values in arterial and venous blood into account. The oxygen exchange fraction (OEF%), corresponding to the degree of blood desaturation between the arterial and the venous compartments, and the amount of oxygen released at the tissue level by 100 mL of blood (OEF Vol%) were calculated from the arterial and venous OEC combined with the PO2 and hemoglobin concentration. In hypoxaemic calves investigated in this study, the hemoglobin oxygen affinity, measured under standard conditions, was not modified. On the contrary, in vivo acidosis and hypercapnia induced a decrease in the hemoglobin oxygen affinity in arterial blood, which combined to the decrease in PaO2 led to a reduced hemoglobin saturation degree in the arterial compartment. However, this did not impair the oxygen exchange fraction (OEF%), since the hemoglobin saturation degree in venous blood was also diminished.

Practical considerations in the development of hemoglobin-based oxygen therapeutics.

PubMed

Kim, Hae Won; Estep, Timothy N

2012-09-01

The development of hemoglobin based oxygen therapeutics (HBOCs) requires consideration of a number of factors. While the enabling technology derives from fundamental research on protein biochemistry and biological interactions, translation of these research insights into usable medical therapeutics demands the application of considerable technical expertise and consideration and reconciliation of a myriad of manufacturing, medical, and regulatory requirements. The HBOC development challenge is further exacerbated by the extremely high intravenous doses required for many of the indications contemplated for these products, which in turn implies an extremely high level of purity is required. This communication discusses several of the important product configuration and developmental considerations that impact the translation of fundamental research discoveries on HBOCs into usable medical therapeutics.

Molecularly imprinted composite cryogels for hemoglobin depletion from human blood.

PubMed

Baydemir, Gözde; Andaç, Müge; Perçin, Işιk; Derazshamshir, Ali; Denizli, Adil

2014-09-01

A molecularly imprinted composite cryogel (MICC) was prepared for depletion of hemoglobin from human blood prior to use in proteome applications. Poly(hydroxyethyl methacrylate) based MICC was prepared with high gel fraction yields up to 90%, and characterized by Fourier transform infrared spectrophotometer, scanning electron microscopy, swelling studies, flow dynamics and surface area measurements. MICC exhibited a high binding capacity and selectivity for hemoglobin in the presence of immunoglobulin G, albumin and myoglobin. MICC column was successfully applied in fast protein liquid chromatography system for selective depletion of hemoglobin for human blood. The depletion ratio was highly increased by embedding microspheres into the cryogel (93.2%). Finally, MICC can be reused many times with no apparent decrease in hemoglobin adsorption capacity. Copyright © 2014 John Wiley & Sons, Ltd.

HbA1c levels in individuals heterozygous for hemoglobin variants.

PubMed

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.

Regulation of nonsymbiotic and truncated hemoglobin genes of Lotus japonicus in plant organs and in response to nitric oxide and hormones.

PubMed

Bustos-Sanmamed, Pilar; Tovar-Méndez, Alejandro; Crespi, Martin; Sato, Shusei; Tabata, Satoshi; Becana, Manuel

2011-02-01

• In legumes, symbiotic leghemoglobins facilitate oxygen diffusion to the bacteroids, but the roles of nonsymbiotic and truncated hemoglobins are largely unknown. Here the five hemoglobin genes of Lotus japonicus have been functionally characterized to gain insight into their regulatory mechanisms. • Plants were exposed to nitric oxide donors, stressful conditions, and hormones. Gene expression profiling was determined by quantitative PCR, and gene activities were localized using in situ hybridization and promoter-reporter gene fusions. • The LjGLB1-1, LjGLB2, and LjGLB3-1 mRNA expression levels were very high in nodules relative to other plant organs. The expression of these genes was localized in the vascular bundles, cortex, and infected tissue. LjGLB1-1 was the only gene induced by nitric oxide. Cytokinins caused nearly complete inactivation of LjGLB2 and LjGLB3-1 in nodules and induction of LjGLB1-1 in roots. Abscisic acid induced LjGLB1-1 in nodules and LjGLB1-2 and LjGLB2 in roots, whereas polyamines and jasmonic acid induced LjGLB1-1 only in roots. • The enhanced expression of the three types of hemoglobins in nodules, the colocalization of gene activities in nodule and root tissues with high metabolic rates, and their distinct regulatory mechanisms point out complementary roles of hemoglobins and strongly support the hypothesis that LjGLB1-1, LjGLB2, and LjGLB3-1 are required for symbiosis. © 2010 The Authors. New Phytologist © 2010 New Phytologist Trust.

Non-invasive prediction of hemoglobin levels by principal component and back propagation artificial neural network

PubMed Central

Ding, Haiquan; Lu, Qipeng; Gao, Hongzhi; Peng, Zhongqi

2014-01-01

To facilitate non-invasive diagnosis of anemia, specific equipment was developed, and non-invasive hemoglobin (HB) detection method based on back propagation artificial neural network (BP-ANN) was studied. In this paper, we combined a broadband light source composed of 9 LEDs with grating spectrograph and Si photodiode array, and then developed a high-performance spectrophotometric system. By using this equipment, fingertip spectra of 109 volunteers were measured. In order to deduct the interference of redundant data, principal component analysis (PCA) was applied to reduce the dimensionality of collected spectra. Then the principal components of the spectra were taken as input of BP-ANN model. On this basis we obtained the optimal network structure, in which node numbers of input layer, hidden layer, and output layer was 9, 11, and 1. Calibration and correction sample sets were used for analyzing the accuracy of non-invasive hemoglobin measurement, and prediction sample set was used for testing the adaptability of the model. The correlation coefficient of network model established by this method is 0.94, standard error of calibration, correction, and prediction are 11.29g/L, 11.47g/L, and 11.01g/L respectively. The result proves that there exist good correlations between spectra of three sample sets and actual hemoglobin level, and the model has a good robustness. It is indicated that the developed spectrophotometric system has potential for the non-invasive detection of HB levels with the method of BP-ANN combined with PCA. PMID:24761296

Individualized drug dosing using RBF-Galerkin method: Case of anemia management in chronic kidney disease.

PubMed

Mirinejad, Hossein; Gaweda, Adam E; Brier, Michael E; Zurada, Jacek M; Inanc, Tamer

2017-09-01

Anemia is a common comorbidity in patients with chronic kidney disease (CKD) and is frequently associated with decreased physical component of quality of life, as well as adverse cardiovascular events. Current treatment methods for renal anemia are mostly population-based approaches treating individual patients with a one-size-fits-all model. However, FDA recommendations stipulate individualized anemia treatment with precise control of the hemoglobin concentration and minimal drug utilization. In accordance with these recommendations, this work presents an individualized drug dosing approach to anemia management by leveraging the theory of optimal control. A Multiple Receding Horizon Control (MRHC) approach based on the RBF-Galerkin optimization method is proposed for individualized anemia management in CKD patients. Recently developed by the authors, the RBF-Galerkin method uses the radial basis function approximation along with the Galerkin error projection to solve constrained optimal control problems numerically. The proposed approach is applied to generate optimal dosing recommendations for individual patients. Performance of the proposed approach (MRHC) is compared in silico to that of a population-based anemia management protocol and an individualized multiple model predictive control method for two case scenarios: hemoglobin measurement with and without observational errors. In silico comparison indicates that hemoglobin concentration with MRHC method has less variation among the methods, especially in presence of measurement errors. In addition, the average achieved hemoglobin level from the MRHC is significantly closer to the target hemoglobin than that of the other two methods, according to the analysis of variance (ANOVA) statistical test. Furthermore, drug dosages recommended by the MRHC are more stable and accurate and reach the steady-state value notably faster than those generated by the other two methods. The proposed method is highly efficient for the control of hemoglobin level, yet provides accurate dosage adjustments in the treatment of CKD anemia. Copyright © 2017 Elsevier B.V. All rights reserved.

Hemoglobin Function in Stored Blood.

DTIC Science & Technology

1974-08-01

States during 1973. Several advantages over ACA) are important. Blood stored in CPD maintains higher ./ levels of 2,3-DPG (2,3- diphosphoglycerate ) and a...survival and ATP levels in stored blood is explained by the several functions of ATP which are necessary for cell viability. However, ATP levels do...not correlate with oxygen affinity during storage. Levels of 2,3-DPG determine oxygen affinity and thus hemoglobin function. (12,13) When normal levels

Clinical Practice Guidelines From the AABB: Red Blood Cell Transfusion Thresholds and Storage.

PubMed

Carson, Jeffrey L; Guyatt, Gordon; Heddle, Nancy M; Grossman, Brenda J; Cohn, Claudia S; Fung, Mark K; Gernsheimer, Terry; Holcomb, John B; Kaplan, Lewis J; Katz, Louis M; Peterson, Nikki; Ramsey, Glenn; Rao, Sunil V; Roback, John D; Shander, Aryeh; Tobian, Aaron A R

2016-11-15

More than 100 million units of blood are collected worldwide each year, yet the indication for red blood cell (RBC) transfusion and the optimal length of RBC storage prior to transfusion are uncertain. To provide recommendations for the target hemoglobin level for RBC transfusion among hospitalized adult patients who are hemodynamically stable and the length of time RBCs should be stored prior to transfusion. Reference librarians conducted a literature search for randomized clinical trials (RCTs) evaluating hemoglobin thresholds for RBC transfusion (1950-May 2016) and RBC storage duration (1948-May 2016) without language restrictions. The results were summarized using the Grading of Recommendations Assessment, Development and Evaluation method. For RBC transfusion thresholds, 31 RCTs included 12 587 participants and compared restrictive thresholds (transfusion not indicated until the hemoglobin level is 7-8 g/dL) with liberal thresholds (transfusion not indicated until the hemoglobin level is 9-10 g/dL). The summary estimates across trials demonstrated that restrictive RBC transfusion thresholds were not associated with higher rates of adverse clinical outcomes, including 30-day mortality, myocardial infarction, cerebrovascular accident, rebleeding, pneumonia, or thromboembolism. For RBC storage duration, 13 RCTs included 5515 participants randomly allocated to receive fresher blood or standard-issue blood. These RCTs demonstrated that fresher blood did not improve clinical outcomes. It is good practice to consider the hemoglobin level, the overall clinical context, patient preferences, and alternative therapies when making transfusion decisions regarding an individual patient. Recommendation 1: a restrictive RBC transfusion threshold in which the transfusion is not indicated until the hemoglobin level is 7 g/dL is recommended for hospitalized adult patients who are hemodynamically stable, including critically ill patients, rather than when the hemoglobin level is 10 g/dL (strong recommendation, moderate quality evidence). A restrictive RBC transfusion threshold of 8 g/dL is recommended for patients undergoing orthopedic surgery, cardiac surgery, and those with preexisting cardiovascular disease (strong recommendation, moderate quality evidence). The restrictive transfusion threshold of 7 g/dL is likely comparable with 8 g/dL, but RCT evidence is not available for all patient categories. These recommendations do not apply to patients with acute coronary syndrome, severe thrombocytopenia (patients treated for hematological or oncological reasons who are at risk of bleeding), and chronic transfusion-dependent anemia (not recommended due to insufficient evidence). Recommendation 2: patients, including neonates, should receive RBC units selected at any point within their licensed dating period (standard issue) rather than limiting patients to transfusion of only fresh (storage length: <10 days) RBC units (strong recommendation, moderate quality evidence). Research in RBC transfusion medicine has significantly advanced the science in recent years and provides high-quality evidence to inform guidelines. A restrictive transfusion threshold is safe in most clinical settings and the current blood banking practices of using standard-issue blood should be continued.

Hemoglobin drop after anesthesia in craniosynstosis: Dilemma of operate or not to operate

PubMed Central

El-Ghandour, Nihal; Kassem, Salah; Al Sabbagh, Abdelrahman J.; Al-Banyan, Ayman; Shubbak, Firas A.; Hassib, Ahmad; Zaki, Hazem

2011-01-01

An infant with craniosynostosis for craniectomy and cranial-vault remodelling was detected to have very low hemoglobin (6.8 gm%) after induction of anesthesia. This posed a dilemma whether to proceed with or abandon the surgical procedure. The case was postponed and was rescheduled for surgery one week later with hope that his hemoglobin would rise during this period. However, even before second anesthesia his hemoglobin level was found to be unchanged. Meticulous anesthesia management resulted in uneventful surgical procedure. PMID:25885398

Combined intravenous, topical and oral tranexamic acid administration in total knee replacement: Evaluation of safety in patients with previous thromboembolism and effect on hemoglobin level and transfusion rate.

PubMed

Jansen, Joris A; Lameijer, Joost R C; Snoeker, Barbara A M

2017-10-01

The aims of this study were to investigate the safety of combined intravenous, oral and topical tranexamic acid (TXA) in primary total knee replacement. We assessed dose-related efficacy on hemoglobin level, transfusion, length of stay and thromboembolic complications. In addition, TXA safety in patients with previous history of thromboembolism >12months ago was monitored specifically. From January 2013 until January 2016, 922 patients were included who received TXA after primary total knee replacement. Patients without TXA administration or with thromboembolic events <12months ago were excluded. TXA dosage groups were divided into ≤10mg/kg, >10-25mg/kg and >25-50mg/kg. Between the three TXA groups no significant difference was found in thromboembolic complications (deep venous thrombosis (DVT) and pulmonary embolism (PE)), wound leakage and transfusion rate. For patients with DVT or PE in their history >12months ago specifically, no more complications were noted in higher-TXA-dosage groups compared to the low-dosage group. Length of stay was shorter in the highest-TXA-dosage group compared with lower-dosage groups (median two vs three days). With high TXA dose a smaller difference between pre- and postoperative Hb was found: the >25-50mg/kg TXA group had a 0.419mmol/l smaller decrease in postoperative hemoglobin compared to the lowest-dosage group (P<0.05). Combined intravenous, oral and topical TXA is effective in knee replacement and can safely be given to patients with a thromboembolic history >12months ago. High dosage (>25-50mg/kg) TXA resulted in the smallest decrease in postoperative hemoglobin. Copyright © 2017 Elsevier B.V. All rights reserved.

Optimized retrograde cerebral perfusion reduces ischemic energy depletion.

PubMed

Oda, Teiji; Kimura, Tetsuhiro; Ogata, Yoshitaka; Fujise, Yutaka

2004-01-01

It has been reported that retrograde cerebral perfusion (RCP) provides minimal capillary flow; however, the extent to which RCP can provide aerobic metabolic support is unknown. We evaluated whether perfusate composition optimization for RCP would preserve brain energy metabolism during hypothermic circulatory arrest (HCA) at 20 degrees C in rats. Three types of perfusates were prepared: hemoglobin-free saline, rat red blood cells, and artificial blood substitute (liposome-encapsulated hemoglobin); perfusates were made hypertonic, cooled to 20 degrees C, and oxygenated and CO(2) was administered (pH-stat management). Circulatory arrest was induced in 24 pH-stat-ventilated Wistar rats that had been surface cooled to 20 degrees C; 18 were assigned to the RCP group in which one of the three ( n = 6 each) perfusates was administered via the maxillary vein, and 6 received no perfusion. In two similarly surface-cooled rats (controls), brains were excised when the temperature reached 20 degrees C. After 20 min of RCP or HCA, brains were excised and immediately frozen; brain high-energy phosphates, adenosine, and water content were measured. The liposome-encapsulated hemoglobin perfusate preserved levels of brain tissue adenosine triphosphates and energy charge, but not significantly better than rat red blood cells. Both maintained significantly higher levels than perfusion with oxygenated saline or hypothermic circulatory arrest alone ( P = 0.0419-0.0001), under which regimes high-energy phosphates and energy charge declined to similar low values. RCP with hypertonic solution prevented brain edema. RCP with optimized composition perfusate (pH-stat, hypertonic rat red blood cells or liposome-encapsulated hemoglobin) reduced ischemic energy depletion during 20 min of HCA at 20 degrees C in rats.

Anemia among HIV-Infected Patients Initiating Antiretroviral Therapy in South Africa: Improvement in Hemoglobin regardless of Degree of Immunosuppression and the Initiating ART Regimen.

PubMed

Takuva, Simbarashe; Maskew, Mhairi; Brennan, Alana T; Sanne, Ian; Macphail, A Patrick; Fox, Mathew P

2013-01-01

Among those with HIV, anemia is a strong risk factor for disease progression and death independent of CD4 count and viral load. Understanding the role of anemia in HIV treatment is critical to developing strategies to reduce morbidity and mortality. We conducted a prospective analysis among 10,259 HIV-infected adults initiating first-line ART between April 2004 and August 2009 in Johannesburg, South Africa. The prevalence of anemia at ART initiation was 25.8%. Mean hemoglobin increased independent of baseline CD4. Females, lower BMI, WHO stage III/IV, lower CD4 count, and zidovudine use were associated with increased risk of developing anemia during follow-up. After initiation of ART, hemoglobin improved, regardless of regimen type and the degree of immunosuppression. Between 0 and 6 months on ART, the magnitude of hemoglobin increase was linearly related to CD4 count. However, between 6 and 24 months on ART, hemoglobin levels showed a sustained overall increase, the magnitude of which was similar regardless of baseline CD4 level. This increase in hemoglobin was seen even among patients on zidovudine containing regimens. Since low hemoglobin is an established adverse prognostic marker, prompt identification of anemia may result in improved morbidity and mortality of patients initiating ART.

[Molecular-genetic basis of regulation of the synthesis of individual types of hemoglobin].

PubMed

Starodub, N F

1980-01-01

The data on the control of ontogenetic hemoglobin type synthesis were analyzed in normal and pathological human and animal organisms. The assumption is made that such control depends on the level of erythroid cell differentiation and erythropoetic factors activity. The latters act as a trigger in switching of qualitative hemoglobin production.

[The overweight, the obesity and the glycemic control among diabetics of the provincial reference center of diabetes (CRD), Kenitra, Morocco].

PubMed

Lotfi, Zeghari; Aboussaleh, Youssef; Sbaibi, Rachid; Achouri, Imane; Benguedour, Rachid

2017-01-01

Diabetes is a disorder of assimilation, use and storage of sugars provided in the diet. Its management is based on follow-up of overweight and obese patients and on regular glycemic control. This study aimed to analyze overweight, obesity and glycemic control in 2227 patients with different types of diabetes (type 1, 2 and gestational) presenting to the Provincial referral center of diabetes (RCD) in Kenitra, Morocco. We conducted a study over the period January-December 2015. Overweight and obesity assessment was performed using Body Mass Index calculator (BMI = weight/height 2 (kg/m 2 ). Overweight and obesity were defined by BMI > 25 kg/m 2 and BMI > 30 kg/m 2 respectively; the weight and the height were measured according to World Health Organization's recommendations. Glycemic control was based on glycated hemoglobin levels and fasting blood glucose test. Current guidelines recommend a glycosylated hemoglobin level of 7% and a fasting blood glucose of 0.70g/l - 1.10g/L. The age of patients ranged from 8 months to 80 years, with a prevalence of diabetic patients from the urban environment (74%) compared to those from the rural areas (26%). The entire study population was overweight. The average BMI of women showed a trend toward obesity (BMI≈30): (29.21 kg/m 2 ± 3,1) in patients with gestational diabetes and (29.15 kg/m 2 ± 3.2) in patients with type 2 diabetes. Blood sugar levels were above the standards: 8.5% ± 2.6 > 7% for glycosylated hemoglobin and 1.5 g/L ± 1.3>1.10g/L for fasting blood glucose. The difference between glycosylated hemoglobin levels between men (8.57% ± 2.6) and women (8.1% ± 2.3) were not significant (p > 0.05), it was the same with fasting blood glucose: men (1.44 g/L ± 1,1) and women (1.43 g/L ± 1.2). Pearson's correlation coefficients were highly significant (p<0.005); on the one hand between BMI and fasting blood glucose(r = 0.5) and on the other hand between BMI and glycosylated hemoglobin levels (r = 0.4). The entire study population had BMI and glycaemic control levels above the standards. More research is needed on diabetic patients in order to develop a remediation plan.

Hemoglobin adducts as biomarkers of 1,3-butadiene in occupationally low exposed Italian workers and a few diesel-exposed miners.

PubMed

Begemann, P; Upton, P B; Ranasinghe, A; Swenberg, J A; Soleo, L; Vimercati, L; Gelormini, A; Fustinoni, S; Zwirner-Baier, I; Neumann, H G

2001-06-01

Hemoglobin adducts were determined as biomarkers of 1,3-butadiene (BD) in 30 workers and 10 controls from an Italian BD plant and in 14 diesel-exposed miners. N-(2,3,4-trihydroxybutyl)valine (THBVal), an N-terminal valine globin adduct of reactive butadiene metabolites, was analyzed by gas chromatography/high resolution mass spectrometry after a modified Edman degradation and further acetylation. The BD exposure for the plant workers was 31 microg/m(3) (personal sampling). Whereas there was no detectable difference in hemoglobin adduct levels (range 17.7-61.4 pmol/g globin) between the total group of exposed and controls, slight but significant differences could be found between two subgroups of workers from different production units as well as one subgroup and controls (P<0.05), between smoking (n=13) and non-smoking exposed workers (n=17; P=0.066) as well as between smoking exposed workers and controls (P=0.055). Adduct levels of the miners (all non-smokers) were in the same range as those of the Italian BD-workers and controls. The internal exposure and strain measured by THBVal levels resulting from a very low occupational BD exposure was in the range of the contribution of moderate smoking.

Tendency for oxidation of annelid hemoglobin at alkaline pH and dissociated states probed by redox titration.

PubMed

Bispo, Jose Ailton Conceicao; Landini, Gustavo Fraga; Santos, Jose Luis Rocha; Norberto, Douglas Ricardo; Bonafe, Carlos Francisco Sampaio

2005-08-01

The redox titration of extracellular hemoglobin of Glossoscolex paulistus (Annelidea) was investigated in different pH conditions and after dissociation induced by pressure. Oxidation increased with increasing pH, as shown by the reduced amount of ferricyanide necessary for the oxidation of hemoglobin. This behavior was the opposite of that of vertebrate hemoglobins. The potential of half oxidation (E1/2) changed from -65.3 to +146.8 mV when the pH increased from 4.50 to 8.75. The functional properties indicated a reduction in the log P50 from 1.28 to 0.28 in this pH range. The dissociation at alkaline pH or induced by high pressure, confirmed by HPLC gel filtration, suggested that disassembly of the hemoglobin could be involved in the increased potential for oxidation. These results suggest that the high stability and prolonged lifetime common to invertebrate hemoglobins is related to their low tendency to oxidize at acidic pH, in contrast to vertebrate hemoglobins.

Insensitivity of cerebral oxygen transport to oxygen affinity of hemoglobin-based oxygen carriers.

PubMed

Koehler, Raymond C; Fronticelli, Clara; Bucci, Enrico

2008-10-01

The cerebrovascular effects of exchange transfusion of various cell-free hemoglobins that possess different oxygen affinities are reviewed. Reducing hematocrit by transfusion of a non-oxygen-carrying solution dilates pial arterioles on the brain surface and increases cerebral blood flow to maintain a constant bulk oxygen transport to the brain. In contrast, transfusion of hemoglobins with P50 of 4-34 Torr causes constriction of pial arterioles that offsets the decrease in blood viscosity to maintain cerebral blood flow and oxygen transport. The autoregulatory constriction is dependent on synthesis of 20-HETE from arachidonic acid. This oxygen-dependent reaction is apparently enhanced by facilitated oxygen diffusion from the red cell to the endothelium arising from increased plasma oxygen solubility in the presence of low or high-affinity hemoglobin. Exchange transfusion of recombinant hemoglobin polymers with P50 of 3 and 18 Torr reduces infarct volume from experimental stroke. Cell-free hemoglobins do not require a P50 as high as red blood cell hemoglobin to facilitate oxygen delivery.

Transcriptional regulation of fetal to adult hemoglobin switching: new therapeutic opportunities

PubMed Central

Wilber, Andrew; Nienhuis, Arthur W.

2011-01-01

In humans, embryonic, fetal, and adult hemoglobins are sequentially expressed in developing erythroblasts during ontogeny. For the past 40 years, this process has been the subject of intensive study because of its value to enlighten the biology of developmental gene regulation and because fetal hemoglobin can significantly ameliorate the clinical manifestations of both sickle cell disease and β-thalassemia. Understanding the normal process of loss of fetal globin expression and activation of adult globin expression could potentially lead to new therapeutic approaches for these hemoglobin disorders. Herein, we briefly review the history of the study of hemoglobin switching and then focus on recent discoveries in the field that now make new therapeutic approaches seem feasible in the future. Erythroid-specific knockdown of fetal gene repressors or enforced expression of fetal gene activators may provide clinically applicable approaches for genetic treatment of hemoglobin disorders that would benefit from increased fetal hemoglobin levels. PMID:21321359

Modulatory effects of naringin on hepatic key enzymes of carbohydrate metabolism in high-fat diet/low-dose streptozotocin-induced diabetes in rats.

PubMed

Pari, Leelavinothan; Chandramohan, Ramasamy

2017-07-01

We evaluated the modulatory effects of naringin on altered hepatic key enzymes of carbohydrate metabolism in high-fat diet/low-dose streptozotocin-induced diabetic rats. Oral treatment of naringin at a doses of 20, 40 and 80 mg/kg body weight to diabetic rats for 30 days resulted in a significant reduction in the levels of plasma glucose, blood glycosylated hemoglobin and increase in the levels of plasma insulin and blood hemoglobin. The altered activities of the hepatic key enzymes of carbohydrate metabolism such as hexokinase, glucose-6-phosphatase, fructose-1,6-bisphosphatase, glucose-6-phosphate dehydrogenase, glycogen synthase, glycogen phosphorylase and glycogen content of diabetic rats were significantly reverted to near normal levels by the treatment of naringin in a dose-dependent manner. Naringin at a dose of 80 mg/kg body weight showed the highest significant effect than the other two doses (20 and 40 mg/kg). Further, immunohistochemical observation of pancreas revealed that naringin-treated diabetic rats showed the increased number of insulin immunoreactive β-cells, which confirmed the biochemical findings. These findings revealed that naringin has potential antihyperglycemic activity in high-fat diet/low-dose streptozotocin-induced diabetic rats.

Nutrition education and knowledge, attitude and hemoglobin status of Malaysian adolescents.

PubMed

Yusoff, Hafzan; Daud, Wan Nudri Wan; Ahmad, Zulkifli

2012-01-01

A higher occurrence of iron deficiency anemia is present in rural Malaysia than urban Malaysia due to a lower socio-economic status of rural residents. This study was conducted in Tanah Merah, a rural district of Kelantan, Malaysia. Our objective was to investigate the impact of nutrition education alone, daily iron, folate and vitamin C supplementation or both on knowledge, attitudes and hemoglobin status of adolescent students. Two hundred eighty fourth year secondary students were each assigned by school to 1 of 4 different treatment groups. Each intervention was carried out for 3 months followed by 3 months without treatment. A validated self-reported knowledge and attitude questionnaire was administered; hemoglobin levels were measured before and after intervention. At baseline, no significant difference in hemoglobin was noted among the 4 groups (p = 0.06). The changes in hemoglobin levels at 3 months were 11, 4.6, 3.9 and -3.7% for the supplementation, nutrition education, combination and control groups, respectively. The changes at 6 months were 1.0, 6.8, 3.7 and -14.8%, respectively. Significant improvements in knowledge and attitude were evidenced in both the nutritional education and combination groups. The supplementation and control groups had no improvement in knowledge or attitudes. This study suggests nutritional education increases knowledge, attitudes and hemoglobin levels among Malaysian secondary school adolescents.

Adaptation and evolution of deep-sea scale worms (Annelida: Polynoidae): insights from transcriptome comparison with a shallow-water species

NASA Astrophysics Data System (ADS)

Zhang, Yanjie; Sun, Jin; Chen, Chong; Watanabe, Hiromi K.; Feng, Dong; Zhang, Yu; Chiu, Jill M. Y.; Qian, Pei-Yuan; Qiu, Jian-Wen

2017-04-01

Polynoid scale worms (Polynoidae, Annelida) invaded deep-sea chemosynthesis-based ecosystems approximately 60 million years ago, but little is known about their genetic adaptation to the extreme deep-sea environment. In this study, we reported the first two transcriptomes of deep-sea polynoids (Branchipolynoe pettiboneae, Lepidonotopodium sp.) and compared them with the transcriptome of a shallow-water polynoid (Harmothoe imbricata). We determined codon and amino acid usage, positive selected genes, highly expressed genes and putative duplicated genes. Transcriptome assembly produced 98,806 to 225,709 contigs in the three species. There were more positively charged amino acids (i.e., histidine and arginine) and less negatively charged amino acids (i.e., aspartic acid and glutamic acid) in the deep-sea species. There were 120 genes showing clear evidence of positive selection. Among the 10% most highly expressed genes, there were more hemoglobin genes with high expression levels in both deep-sea species. The duplicated genes related to DNA recombination and metabolism, and gene expression were only enriched in deep-sea species. Deep-sea scale worms adopted two strategies of adaptation to hypoxia in the chemosynthesis-based habitats (i.e., rapid evolution of tetra-domain hemoglobin in Branchipolynoe or high expression of single-domain hemoglobin in Lepidonotopodium sp.).

Adaptation and evolution of deep-sea scale worms (Annelida: Polynoidae): insights from transcriptome comparison with a shallow-water species

PubMed Central

Zhang, Yanjie; Sun, Jin; Chen, Chong; Watanabe, Hiromi K.; Feng, Dong; Zhang, Yu; Chiu, Jill M.Y.; Qian, Pei-Yuan; Qiu, Jian-Wen

2017-01-01

Polynoid scale worms (Polynoidae, Annelida) invaded deep-sea chemosynthesis-based ecosystems approximately 60 million years ago, but little is known about their genetic adaptation to the extreme deep-sea environment. In this study, we reported the first two transcriptomes of deep-sea polynoids (Branchipolynoe pettiboneae, Lepidonotopodium sp.) and compared them with the transcriptome of a shallow-water polynoid (Harmothoe imbricata). We determined codon and amino acid usage, positive selected genes, highly expressed genes and putative duplicated genes. Transcriptome assembly produced 98,806 to 225,709 contigs in the three species. There were more positively charged amino acids (i.e., histidine and arginine) and less negatively charged amino acids (i.e., aspartic acid and glutamic acid) in the deep-sea species. There were 120 genes showing clear evidence of positive selection. Among the 10% most highly expressed genes, there were more hemoglobin genes with high expression levels in both deep-sea species. The duplicated genes related to DNA recombination and metabolism, and gene expression were only enriched in deep-sea species. Deep-sea scale worms adopted two strategies of adaptation to hypoxia in the chemosynthesis-based habitats (i.e., rapid evolution of tetra-domain hemoglobin in Branchipolynoe or high expression of single-domain hemoglobin in Lepidonotopodium sp.). PMID:28397791

21 CFR 864.7470 - Glycosylated hemoglobin assay.

Code of Federal Regulations, 2013 CFR

2013-04-01

... diabetes and to determine the proper insulin dosage for a patient. Elevated levels of glycosylated hemoglobin indicate uncontrolled diabetes in a patient. (b) Classification. Class II (performance standards...

21 CFR 864.7470 - Glycosylated hemoglobin assay.

Code of Federal Regulations, 2012 CFR

2012-04-01

... diabetes and to determine the proper insulin dosage for a patient. Elevated levels of glycosylated hemoglobin indicate uncontrolled diabetes in a patient. (b) Classification. Class II (performance standards...

21 CFR 864.7470 - Glycosylated hemoglobin assay.

Code of Federal Regulations, 2014 CFR

2014-04-01

... diabetes and to determine the proper insulin dosage for a patient. Elevated levels of glycosylated hemoglobin indicate uncontrolled diabetes in a patient. (b) Classification. Class II (performance standards...

21 CFR 864.7470 - Glycosylated hemoglobin assay.

Code of Federal Regulations, 2010 CFR

2010-04-01

... diabetes and to determine the proper insulin dosage for a patient. Elevated levels of glycosylated hemoglobin indicate uncontrolled diabetes in a patient. (b) Classification. Class II (performance standards...

The anemia of primary autonomic failure and its reversal with recombinant erythropoietin

NASA Technical Reports Server (NTRS)

Biaggioni, I.; Robertson, D.; Krantz, S.; Jones, M.; Haile, V.

1994-01-01

OBJECTIVE: To determine if chronic sympathetic deprivation is associated with anemia and a low erythropoietin response. DESIGN: Survey of the prevalence and characteristics of anemia in patients with severe primary autonomic failure. SETTING: A referral service for autonomic failure in a tertiary teaching hospital. PATIENTS: 84 patients with primary autonomic failure who had symptomatic orthostatic hypotension. INTERVENTION: Open-label trial with human recombinant erythropoietin. RESULTS: Anemia was present in 32 of 84 patients (38%; 95% Cl, 27% to 50%). Plasma norepinephrine levels, measured in patients standing upright, were lower in the patient group with lower hemoglobin levels. Mean values in 22 patients with a hemoglobin level of less than 120 g/L were as follows: hemoglobin, 108 g/L (range, 87 to 118 g/L); hematocrit, 0.33; corrected reticulocyte counts, 0.008; mean corpuscular volume, 89 fL (89 microns 3); serum iron, 16.5 mumol/L (92 micrograms/dL); total iron binding capacity, 43.3 mumol/L (242 micrograms/dL); ferritin, 184 micrograms/L; serum vitamin B12, 410 pmol/L (556 pg/mL); and serum folate, 22.7 nmol/L (10 ng/mL). No relation was found between serum erythropoietin and blood hemoglobin levels. In seven of nine patients with autonomic failure who had hemoglobin levels less than 120 g/L, serum erythropoietin levels decreased below the 95% confidence interval corresponding to patients with iron deficiency anemia. Therapy with recombinant erythropoietin improved mean hemoglobin levels (from 108 to 133 g/L) in all patients treated (n = 5) at relatively low doses (25 to 50 units/kg body weight, subcutaneously, three times a week). CONCLUSIONS: Our data support the hypothesis that the sympathetic nervous system stimulates erythropoiesis in humans because anemia is a frequent occurrence in patients with severe autonomic failure and is associated with a blunted erythropoietin response.

Crystal structure analysis of Great Cormorant (Phalacrocorax carbo) Hemoglobin.

PubMed

Ganapathy, Jagadeesan; Palayam, Malathy; Pennathur, Gautam; Sanmargam, Aravindhan; Krishnasamy, Gunasekaran

2018-06-20

Hemoglobin (Hb) molecule consists of α2β2 dimers arranged in fashion having pseudo-222 symmetry. The subunits are composed of the specific functional prosthetic group "heme'' and a protein moiety "globin". Bird Hbs are functionally similar to mammalian Hbs and regulated by inositol pentaphosphate (IPP) but they are structurally dissimilar with mammalian Hbs in adaptation to vital environment such as high altitudes, high speed flights and oxygen affinity. The insufficient structural studies on avian Hbs limit us to understand their degree of adaptation to such critical environments. So far, detailed structural studies of bar-headed goose (BHG) and graylag goose (GLG) Hb structures were reported to expose their remarkable difference in molecular level adaptation. The striking contrasts to its close relative the bar headed goose, which lives at high altitude and capable of tolerating severe hypoxic environment is mainly due its structural features. The Great Cormorant (GCT) can fly and swim, the dual characteristic of GCT leads to study the details of adaptation of high oxygen affinity in avian species and to know about the role of amino acid substitutions at α1β1 interface, the crystal structure of Great cormorant is studied. The structure of GCT Hb has been solved at 3.5Å resolution and it is compared with the other high oxygen affinity Hb (graylag goose (GLG), bar headed goose (BHG) and human (HMN) hemoglobin) structures. To determine the crystal structure of Great Cormorant (GCT) Hemoglobin and to compare its three dimensional structure with other high and low oxygen affinity hemoglobin species to understand its characteristic features of high oxygen affinity. The GCT hemoglobin has been purified, crystallized and data sets were processed using iMosflm. The integrated data has been solved using Molecular replacement method using Graylag hemoglobin (1FAW) as the template. The structure refinement has been carried out using Refmac which reduced the Rwork and Rfree to 23% and 27% respectively. The structure has been deposited in Protein Data Bank with PDB code: 3WR1. The Great cormorant hemoglobin consists of 287 amino acids, two heme and one water molecule located in alpha heme site. The structure has been crystallized in a tetragonal system having half a molecule in the assymetric unit. In order to characterize the tertiary and quaternary structural differences, the structure of cormorant hemoglobin is compared with GLG, BHG and human Hb. The larger variation observed between GCT and human Hb indicates that GCT Hb differs remarkably from human. The α1β1 interface of Great cormorant Hb is similar to bar-headed goose Hb with few amino acid substitutions. It has been found that the interaction which is common among avian hemoglobins (α119 Pro- β55Leu) is altered by Ala 119 in GCT. This intra-dimer contact (α119 Pro - β 55 Leu) disruption leads to high oxygen affinity in BGH Hb. In cormorant, GLG and human the proline is unchanged but interestingly, in cormorant Hb, the β55 position was found to be Thr instead of Leu. Similar kind of substitutions (β 55 Leu - Ser) observed in Andean goose Hb structure leads to elevated oxygen affinity between Hb-O2. To our surprise, such type of substitution at β 55 (Thr) in cormorant Hb confirms that it is comparable with Andean goose Hb structure. Thus the sequence, structural differences at alpha, beta heme pocket and interface contacts confirms that GCT adopts high oxygen affinity conformation. The three dimensional structure of Great cormorant hemoglobin has been investigated to understand its unique structural features to adopt during hypoxia condition. The comparative studies of GCT's α, β heme pockets and the subunit interface with other Hbs reveal its similarities with goose Hbs. Also the loss of α119 - β55 contact in GCT and its unique mutation (Leu β55 Thr ) as in goose Hbs may play an important role in oxygen affinity. Thus by comparing the sequence and overall structural similarities with high and low oxygen affinity species, it appears that GCT has more possibilities to subsist with low oxygen demand. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Structural and functional properties of hemoglobins from unicellular organisms as revealed by resonance Raman spectroscopy.

PubMed

Egawa, Tsuyoshi; Yeh, Syun-Ru

2005-01-01

Hemoglobins have been discovered in organisms from virtually all kingdoms. Their presence in unicellular organisms suggests that the gene for hemoglobin is very ancient and that the hemoglobins must have functions other than oxygen transport, in view of the fact that O2 delivery is a diffusion-controlled process in these organisms. Based on sequence alignment, three groups of hemoglobins have been characterized in unicellular organisms. The group-one hemoglobins, termed truncated hemoglobins, consist of proteins with 110-140 amino acid residues and a novel two-over-two alpha-helical sandwich motif. The group-two hemoglobins, termed flavohemoglobins, consist of a hemoglobin domain, with a classical three-over-three alpha-helical sandwich motif, and a flavin-containing reductase domain that is covalently attached to it. The group-three hemoglobins consist of myoglobin-like proteins that have high sequence homology and structural similarity to the hemoglobin domain of flavohemoglobins. In this review, recent resonance Raman studies of each group of these proteins are presented. Their implications are discussed in the context of the structural and functional properties of these novel hemoglobins.

Hemopressins and other hemoglobin-derived peptides in mouse brain: Comparison between brain, blood, and heart peptidome and regulation in Cpefat/fat mice

PubMed Central

Gelman, Julia S.; Sironi, Juan; Castro, Leandro M.; Ferro, Emer S.; Fricker, Lloyd D.

2010-01-01

Many hemoglobin-derived peptides are present in mouse brain, and several of these have bioactive properties including the hemopressins, a related series of peptides that bind to cannabinoid CB1 receptors. Although hemoglobin is a major component of red blood cells, it is also present in neurons and glia. To examine whether the hemoglobin-derived peptides in brain are similar to those present in blood and heart, we used a peptidomics approach involving mass spectrometry. Many hemoglobin-derived peptides are found only in brain and not in blood, whereas all hemoglobin-derived peptides found in heart were also seen in blood. Thus, it is likely that the majority of the hemoglobin-derived peptides detected in brain are produced from brain hemoglobin and not erythrocytes. We also examined if the hemopressins and other major hemoglobin-derived peptides were regulated in the Cpefat/fat mouse; previously these mice were reported to have elevated levels of several hemoglobin-derived peptides. Many, but not all of the hemoglobin-derived peptides were elevated in several brain regions of the Cpefat/fat mouse. Taken together, these findings suggest that the post-translational processing of alpha and beta hemoglobin into the hemopressins, as well as other peptides, is upregulated in some but not all Cpefat/fat mouse brain regions. PMID:20202081

C.E.R.A. administered once monthly corrects and maintains stable hemoglobin levels in chronic kidney disease patients not on dialysis: the observational study MICENAS II.

PubMed

Martínez-Castelao, Alberto; Cases, Aleix; Coll, Elisabeth; Bonal, Jordi; Galceran, Josep M; Fort, Joan; Moreso, Francesc; Torregrosa, Vicente; Guirado, Lluís; Ruiz, Pilar

2015-01-01

C.E.R.A. (continuous erythropoietin receptor activator, pegilated-rHuEPO ß) corrects and maintains stable hemoglobin levels in once-monthly administration in chronic kidney disease (CKD) patients. The aim of this study was to evaluate the management of anemia with C.E.R.A. in CKD patients not on dialysis in the clinical setting. Two hundred seventy two anemic CKD patients not on dialysis treated with C.E.R.A. were included in this retrospective, observational, multicentric study during 2010. Demographical characteristics, analytical parameters concerning anemia, treatment data and iron status were recorded. C.E.R.A. achieved a good control of anemia in both naïve patients (mean Hemoglobin 11.6g/dL) and patients converted from a previous ESA (mean Hemoglobin 11.7g/dL). Most naïve patients received C.E.R.A. once monthly during the correction phase and required a low monthly dose (median dose 75 µg/month). The same median dose was required in patients converted from a previous ESA, and it was lower than recommended in the Summary of Product Characteristics (SPC). Iron status was adequate in 75% of anemic CKD patients, but only 50% of anemic patients with iron deficiency received iron supplementation. C.E.R.A. corrects and maintains stable hemoglobin levels in anemic CKD patients not on dialysis, requiring conversion doses lower than those recommended by the SPC, and achieving target hemoglobin levels with once-monthly dosing frequency both in naïve and converted patients.

Correlation of Oxygenated Hemoglobin Concentration and Psychophysical Amount on Speech Recognition

NASA Astrophysics Data System (ADS)

Nozawa, Akio; Ide, Hideto

The subjective understanding on oral language understanding task is quantitatively evaluated by the fluctuation of oxygenated hemoglobin concentration measured by the near-infrared spectroscopy. The English listening comprehension test wihch consists of two difficulty level was executed by 4 subjects during the measurement. A significant correlation was found between the subjective understanding and the fluctuation of oxygenated hemoglobin concentration.

Association of hemoglobin A(1c) level with the severity of coronary artery disease in patients with diabetes mellitus.

PubMed

Ravipati, Gautham; Aronow, Wilbert S; Ahn, Chul; Sujata, Kumbar; Saulle, Leonardo N; Weiss, Melvin B

2006-04-01

Coronary angiography was performed in 152 men and 163 women with diabetes mellitus (mean age 55 +/- 8 years) because of chest pain. The mean hemoglobin A(1c) level was 6.66 +/- 0.58% in 132 patients with 0-vessel coronary artery disease (CAD), 8.00 +/- 0.84% in 40 patients with 1-vessel CAD, 8.83 +/- 1.45% in 76 patients with 2-vessel CAD, and 10.40 +/- 2.28% in 67 patients with 3- or 4-vessel CAD. There was a significant increasing trend of hemoglobin A(1c) levels over the increasing number of vessels with CAD (p <0.0001).

Oxygenation level and hemoglobin concentration in experimental tumor estimated by diffuse optical spectroscopy

NASA Astrophysics Data System (ADS)

Orlova, A. G.; Kirillin, M. Yu.; Volovetsky, A. B.; Shilyagina, N. Yu.; Sergeeva, E. A.; Golubiatnikov, G. Yu.; Turchin, I. V.

2017-07-01

Using diffuse optical spectroscopy the level of oxygenation and hemoglobin concentration in experimental tumor in comparison with normal muscle tissue of mice have been studied. Subcutaneously growing SKBR-3 was used as a tumor model. Continuous wave fiber probe diffuse optical spectroscopy system was employed. Optical properties extraction approach was based on diffusion approximation. Decreased blood oxygen saturation level and increased total hemoglobin content were demonstrated in the neoplasm. The main reason of such differences between tumor and norm was significant elevation of deoxyhemoglobin concentration in SKBR-3. The method can be useful for diagnosis of tumors as well as for study of blood flow parameters of tumor models with different angiogenic properties.

Visual Learning Alters the Spontaneous Activity of the Resting Human Brain: An fNIRS Study

PubMed Central

Niu, Haijing; Li, Hao; Sun, Li; Su, Yongming; Huang, Jing; Song, Yan

2014-01-01

Resting-state functional connectivity (RSFC) has been widely used to investigate spontaneous brain activity that exhibits correlated fluctuations. RSFC has been found to be changed along the developmental course and after learning. Here, we investigated whether and how visual learning modified the resting oxygenated hemoglobin (HbO) functional brain connectivity by using functional near-infrared spectroscopy (fNIRS). We demonstrate that after five days of training on an orientation discrimination task constrained to the right visual field, resting HbO functional connectivity and directed mutual interaction between high-level visual cortex and frontal/central areas involved in the top-down control were significantly modified. Moreover, these changes, which correlated with the degree of perceptual learning, were not limited to the trained left visual cortex. We conclude that the resting oxygenated hemoglobin functional connectivity could be used as a predictor of visual learning, supporting the involvement of high-level visual cortex and the involvement of frontal/central cortex during visual perceptual learning. PMID:25243168

Visual learning alters the spontaneous activity of the resting human brain: an fNIRS study.

PubMed

Niu, Haijing; Li, Hao; Sun, Li; Su, Yongming; Huang, Jing; Song, Yan

2014-01-01

Resting-state functional connectivity (RSFC) has been widely used to investigate spontaneous brain activity that exhibits correlated fluctuations. RSFC has been found to be changed along the developmental course and after learning. Here, we investigated whether and how visual learning modified the resting oxygenated hemoglobin (HbO) functional brain connectivity by using functional near-infrared spectroscopy (fNIRS). We demonstrate that after five days of training on an orientation discrimination task constrained to the right visual field, resting HbO functional connectivity and directed mutual interaction between high-level visual cortex and frontal/central areas involved in the top-down control were significantly modified. Moreover, these changes, which correlated with the degree of perceptual learning, were not limited to the trained left visual cortex. We conclude that the resting oxygenated hemoglobin functional connectivity could be used as a predictor of visual learning, supporting the involvement of high-level visual cortex and the involvement of frontal/central cortex during visual perceptual learning.

Lead poisoning in United States-bound refugee children: Thailand-Burma border, 2009.

PubMed

Mitchell, Tarissa; Jentes, Emily; Ortega, Luis; Scalia Sucosky, Marissa; Jefferies, Taran; Bajcevic, Predrag; Parr, Valentina; Jones, Warren; Brown, Mary Jean; Painter, John

2012-02-01

Elevated blood lead levels lead to permanent neurocognitive sequelae in children. Resettled refugee children in the United States are considered at high risk for elevated blood lead levels, but the prevalence of and risk factors for elevated blood lead levels before resettlement have not been described. Blood samples from children aged 6 months to 14 years from refugee camps in Thailand were tested for lead and hemoglobin. Sixty-seven children with elevated blood lead levels (venous ≥10 µg/dL) or undetectable (capillary <3.3 µg/dL) blood lead levels participated in a case-control study. Of 642 children, 33 (5.1%) had elevated blood lead levels. Children aged <2 years had the highest prevalence (14.5%). Among children aged <2 years included in a case-control study, elevated blood lead levels risk factors included hemoglobin <10 g/dL, exposure to car batteries, and taking traditional medicines. The prevalence of elevated blood lead levels among tested US-bound Burmese refugee children was higher than the current US prevalence, and was especially high among children <2 years old. Refugee children may arrive in the United States with elevated blood lead levels. A population-specific understanding of preexisting lead exposures can enhance postarrival lead-poisoning prevention efforts, based on Centers for Disease Control and Prevention recommendations for resettled refugee children, and can lead to remediation efforts overseas.

Cinnamon use in type 2 diabetes: an updated systematic review and meta-analysis.

PubMed

Allen, Robert W; Schwartzman, Emmanuelle; Baker, William L; Coleman, Craig I; Phung, Olivia J

2013-01-01

Cinnamon has been studied in randomized controlled trials (RCTs) for its glycemic-lowering effects, but studies have been small and show conflicting results. A prior meta-analysis did not show significant results, but several RCTs have been published since then. We conducted an updated systematic review and meta-analysis of RCTs evaluating cinnamon's effect on glycemia and lipid levels. MEDLINE, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) were searched through February 2012. Included RCTs evaluated cinnamon compared with control in patients with type 2 diabetes and reported at least one of the following: glycated hemoglobin (A1c), fasting plasma glucose, total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), or triglycerides. Weighted mean differences (with 95% confidence intervals) for endpoints were calculated using random-effects models. In a meta-analysis of 10 RCTs (n = 543 patients), cinnamon doses of 120 mg/d to 6 g/d for 4 to 18 weeks reduced levels of fasting plasma glucose (-24.59 mg/dL; 95% CI, -40.52 to -8.67 mg/dL), total cholesterol (-15.60 mg/dL; 95% CI, -29.76 to -1.44 mg/dL), LDL-C (-9.42 mg/dL; 95% CI, -17.21 to -1.63 mg/dL), and triglycerides (-29.59 mg/dL; 95% CI, -48.27 to -10.91 mg/dL). Cinnamon also increased levels of HDL-C (1.66 mg/dL; 95% CI, 1.09 to 2.24 mg/dL). No significant effect on hemoglobin A1c levels (-0.16%; 95%, CI -0.39% to 0.02%) was seen. High degrees of heterogeneity were present for all analyses except HDL-C (I(2) ranging from 66.5% to 94.72%). The consumption of cinnamon is associated with a statistically significant decrease in levels of fasting plasma glucose, total cholesterol, LDL-C, and triglyceride levels, and an increase in HDL-C levels; however, no significant effect on hemoglobin A1c was found. The high degree of heterogeneity may limit the ability to apply these results to patient care, because the preferred dose and duration of therapy are unclear.

The Relationship Between Hemoglobin Level and Intellectual Function.

ERIC Educational Resources Information Center

Munro, Nancy

In a study to learn whether or not poor nutrition, as indicated by low hemoglobin levels, affects intelligence and behavior, 113 Head Start children in Missoula, Montana took part. Group testing with the Lorge Thorndike Intelligence Test and individual testing with the Wechsler and Primary Scale of Intelligence or Wechsler Intelligence Scale for…

Prevalence of glutathione S-transferase gene deletions and their effect on sickle cell patients.

PubMed

Sanjay, Pandey; Mani, Mishra Rahasy; Sweta, Pandey; Vineet, Shah; Kumar, Ahuja Rajesh; Renu, Saxena

2012-01-01

Glutathione S-transferase gene deletions are known detoxification agents and cause oxidative damage. Due to the different pathophysiology of anemia in thalassemia and sickle cell disease, there are significant differences in the pathophysiology of iron overload and iron-related complications in these disorders. The aim of this study was to estimate the frequency of the GSTM1 and GSTT1 genotypes in sickle cell disease patients and their effect on iron status. Forty sickle cell anemia and sixty sickle ß-thalassemia patients and 100 controls were evaluated to determine the frequency of GST gene deletions. Complete blood counts were performed by an automated cell analyzer. Hemoglobin F, hemoglobin A, hemoglobin A2 and hemoglobin S were measured and diagnosis of patients was achieved by high performance liquid chromatography with DNA extraction by the phenol-chloroform method. The GST null genotype was determined using multiplex polymerase chain reaction and serum ferritin was measured using an ELISA kit. Statistical analysis was by EpiInfo and GraphPad statistics software. An increased frequency of the GSTT1 null genotype (p-value = 0.05) was seen in the patients. The mean serum ferritin level was higher in patients with the GST genotypes than in controls; this was statistically significant for all genotypes except GSTM1, however the higher levels of serum ferritin were due to blood transfusions in patients. GST deletions do not play a direct role in iron overload of sickle cell patients.

Tranexamic acid administration to older patients undergoing primary total hip arthroplasty conserves hemoglobin and reduces blood loss.

PubMed

El Beheiry, Hossam; Lubberdink, Ashley; Clements, Nigel; Dihllon, Kiran; Sharma, Vicky

2018-06-01

Tranexamic acid effects in older people are difficult to predict. This study investigated the following research questions: 1) Is tranexamic acid effective in older patients undergoing primary total hip arthroplasty (THA)? and 2) Is there a difference in the effect of tranexamic acid between younger and older patients? This was a 2-phase retrospective matched-pair study of patients who underwent THA in 2007-2013. All procedures were performed by surgeons with at least 10 years' experience as senior consultant. In the first phase, 58 patients aged 65 years or more who received tranexamic acid were matched 1:1 with patients who did not receive tranexamic acid for age, sex, American Society of Anesthesiologists (ASA) classification and body mass index. In the second phase, 58 patients aged 65 years or more who received tranexamic acid were matched 1:1 with patients less than 65 years of age who received tranexamic acid for sex, ASA classification and body mass index. The primary outcome measures were percent maximum decrease in hemoglobin level and estimated blood loss after surgery. In the first phase, patients who received tranexamic acid conserved postoperative hemoglobin by a mean of 10.26 g/L (standard deviation [SD] 9.89 g/L) compared to the control group ( p < 0.001). The mean difference in the estimated perioperative blood loss between the 2 groups was 410 mL (SD 376 mL) ( p < 0.001), which indicated less bleeding in the treatment group. In the second phase, there was no difference between the younger (mean age 55.1 [SD 7.28] yr) and older (mean age 75.6 [SD 6.35] yr) groups in mean lowest postoperative hemoglobin level or percent decrease in hemoglobin level. Tranexamic acid reduced the postoperative decrease in hemoglobin level and blood loss in older patients. Moreover, the significant hemoglobin-sparing effect of tranexamic acid in older patients was similar to that observed in younger patients.

Three-year efficacy of complex insulin regimens in type 2 diabetes.

PubMed

Holman, Rury R; Farmer, Andrew J; Davies, Melanie J; Levy, Jonathan C; Darbyshire, Julie L; Keenan, Joanne F; Paul, Sanjoy K

2009-10-29

Evidence supporting the addition of specific insulin regimens to oral therapy in patients with type 2 diabetes mellitus is limited. In this 3-year open-label, multicenter trial, we evaluated 708 patients who had suboptimal glycated hemoglobin levels while taking metformin and sulfonylurea therapy. Patients were randomly assigned to receive biphasic insulin aspart twice daily, prandial insulin aspart three times daily, or basal insulin detemir once daily (twice if required). Sulfonylurea therapy was replaced by a second type of insulin if hyperglycemia became unacceptable during the first year of the study or subsequently if glycated hemoglobin levels were more than 6.5%. Outcome measures were glycated hemoglobin levels, the proportion of patients with a glycated hemoglobin level of 6.5% or less, the rate of hypoglycemia, and weight gain. Median glycated hemoglobin levels were similar for patients receiving biphasic (7.1%), prandial (6.8%), and basal (6.9%) insulin-based regimens (P=0.28). However, fewer patients had a level of 6.5% or less in the biphasic group (31.9%) than in the prandial group (44.7%, P=0.006) or in the basal group (43.2%, P=0.03), with 67.7%, 73.6%, and 81.6%, respectively, taking a second type of insulin (P=0.002). [corrected] Median rates of hypoglycemia per patient per year were lowest in the basal group (1.7), higher in the biphasic group (3.0), and highest in the prandial group (5.7) (P<0.001 for the overall comparison). The mean weight gain was higher in the prandial group than in either the biphasic group or the basal group. Other adverse event rates were similar in the three groups. Patients who added a basal or prandial insulin-based regimen to oral therapy had better glycated hemoglobin control than patients who added a biphasic insulin-based regimen. Fewer hypoglycemic episodes and less weight gain occurred in patients adding basal insulin. (Current Controlled Trials number, ISRCTN51125379.) 2009 Massachusetts Medical Society

Characterization of glycidol-hemoglobin adducts as biomarkers of exposure and in vivo dose

DOE Office of Scientific and Technical Information (OSTI.GOV)

Honda, Hiroshi, E-mail: honda.hiroshi@kao.co.jp; Törnqvist, Margareta; Nishiyama, Naohiro

2014-03-15

Hemoglobin adducts have been used as biomarkers of exposure to reactive chemicals. Glycidol, an animal carcinogen, has been reported to form N-(2,3-dihydroxy-propyl)valine adducts to hemoglobin (diHOPrVal). To support the use of these adducts as markers of glycidol exposure, we investigated the kinetics of diHOPrVal formation and its elimination in vitro and in vivo. Five groups of rats were orally administered a single dose of glycidol ranging from 0 to 75 mg/kg bw, and diHOPrVal levels were measured 24 h after administration. A dose-dependent increase in diHOPrVal levels was observed with high linearity (R{sup 2} = 0.943). Blood sampling at differentmore » time points (1, 10, 20, or 40 days) from four groups administered glycidol at 12 mg/kg bw suggested a linear decrease in diHOPrVal levels compatible with the normal turnover of rat erythrocytes (life span, 61 days), with the calculated first-order elimination rate constant (k{sub el}) indicating that the diHOPrVal adduct was chemically stable. Then, we measured the second-order rate constant (k{sub val}) for the reaction of glycidol with N-terminal valine in rat and human hemoglobin in in vitro experiments with whole blood. The k{sub val} was 6.7 ± 1.1 and 5.6 ± 1.3 (pmol/g globin per μMh) in rat and human blood, respectively, indicating no species differences. In vivo doses estimated from k{sub val} and diHOPrVal levels were in agreement with the area under the (concentration–time) curve values determined in our earlier toxicokinetic study in rats. Our results indicate that diHOPrVal is a useful biomarker for quantification of glycidol exposure and for risk assessment. - Highlight: • Glycidol-hemoglobin adduct (diHOPrVal) was characterized for exposure evaluation. • We studied the kinetics of diHOPrVal formation and elimination in vitro and in vivo. • Dose dependent formation and chemical stability were confirmed in the rat study. • In vivo dose (AUC) of glycidol could be estimated from diHOPrVal levels. • diHOPrVal is considered a useful exposure and in vivo dose marker of G.« less

Insensitivity of cerebral oxygen transport to oxygen affinity of hemoglobin-based oxygen carriers

PubMed Central

Koehler, Raymond C.; Fronticelli, Clara; Bucci, Enrico

2008-01-01

The cerebrovascular effects of exchange transfusion of various cell-free hemoglobins that possess different oxygen affinities are reviewed. Reducing hematocrit by transfusion of a non-oxygen-carrying solution dilates pial arterioles on the brain surface and increases cerebral blood flow to maintain a constant bulk oxygen transport to the brain. In contrast, transfusion of hemoglobins with P50 of 4–34 Torr causes constriction of pial arterioles that offsets the decrease in blood viscosity to maintain cerebral blood flow and oxygen transport. The autoregulatory constriction is dependent on synthesis of 20-HETE from arachidonic acid. This oxygen-dependent reaction is apparently enhanced by facilitated oxygen diffusion from the red cell to the endothelium arising from increased plasma oxygen solubility in the presence of low or high-affinity hemoglobin. Exchange transfusion of recombinant hemoglobin polymers with P50 of 3 and 18 Torr reduces infarct volume from experimental stroke. Cell-free hemoglobins do not require a P50 as high as red blood cell hemoglobin to facilitate oxygen delivery. PMID:18230370

Heme Iron Concentrate and Iron Sulfate Added to Chocolate Biscuits: Effects on Hematological Indices of Mexican Schoolchildren.

PubMed

Quintero-Gutiérrez, Adrián Guillermo; González-Rosendo, Guillermina; Pozo, Javier Polo; Villanueva-Sánchez, Javier

2016-08-01

Food fortification is one of the most effective strategies for increasing iron intake in the population. A simple blind trial was conducted to compare the effect of 2 forms of iron fortification and assess the changes in hemoglobin and iron status indices among preschool children from rural communities. Hemoglobin was evaluated in 47 children aged 3-6 years old. For 72 days (10-week period), children ate Nito biscuits. Thirteen pupils with elevated hemoglobin levels were assigned to the biscuit control group, and pupils with hemoglobin equal to 13.5 mg/dL or less were randomly allocated to consume fortified biscuits with a heme iron concentrate (n = 15) or iron sulfate (n = 19). Changes in hemoglobin, plasma ferritin, and other hematological indices were evaluated with analysis of variance (ANOVA) for repeated measurements. Except mean corpuscular hemoglobin concentrations (+1.27 ± 2.25 g/dL), hematological indices increased significantly across the study: Mean corpuscular volume (+2.2 ± 1.0 f/dL), red blood cells (+0.30 ± 0.37 M/μL), mean corpuscular hemoglobin (+1.8 ± 1.74 pg), hemoglobin (+1.68 ± 0.91 g/dL), hematocrit (+3.43% ± 3.03%), and plasma ferritin (+18.38 ± 22.1 μg/L) were all p < 0.05. After 10 weeks, the adjusted effect of the iron-fortified chocolate biscuits in the hemoglobin levels was higher than the control group (+1.1 ± 0.2 g/dL) but no difference was found between consumers of fortified biscuits with heme iron concentrate or iron sulfate (+1.9 ± 0.2 g/dL and +2.0 ± 0.2 g/dL, respectively). Heme iron concentrate and iron sulfate were equally effective in increasing Hb levels and hematological indices. Processed foods were shown to be an effective, valuable, and admissible intervention to prevent anemia in preschool children.

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

PubMed

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 < 0.05 was considered statistically significant for all the tests applied for significance. The association of high 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 < 0.001 and odds ratio was 2.038 (95% confidence interval: 1.397 - 2.972). Logistic regression models were adjusted for demographic factors (age, race, gender), lifestyle factors (smoking, body mass index, lifestyle) and health status factors (blood pressure, physician-rated health status). After adjusting for relevant covariates, glycated hemoglobin was positively correlated with high triglyceride. Hence, HbA1c can be an indicator of triglyceride level and can be one of the predictors of cardiovascular risk factors in type 2 diabetes mellitus.

The relation between hemoglobin variability and carotid intima-media thickness in chronic hemodialysis patients.

PubMed

Ganidagli, Safa Ersen; Altunoren, Orcun; Erken, Ertuğrul; Isık, Ismet Onder; Ganidagli, Berivan; Eren, Necmi; Yavuz, Yasemin Coskun; Gungor, Ozkan

2017-10-01

Hemoglobin variability is a common problem among hemodialysis patients. We have previously demonstrated an association between Hb variability and left ventricular mass index. In this study, we investigated a possible relation between Hb variability and carotid intima-media thickness (CIMT). Twelve-month hemoglobin (Hb) values of 135 patients on maintenance hemodialysis were examined retrospectively. The range of 11-12 gr/dl was accepted as normal according to the KDOQI guidelines. Hemoglobin levels were classified as: Hb < 11 gr/dl:Low, Hb = 11-12 gr/dl:Normal and Hb > 12 gr/dl:High. According to 12-month Hb trajectory, the patients were divided into three groups: low-normal (LN), normal-high (NH) and low-high (LH). The CIMT measurements were taken on common carotid arteries bilaterally, and the average of these measurements were taken. The groups were compared in terms of CIMT measurements, demographic and laboratory features. The LN, NH and LH groups were similar in terms of age, gender, incidence of diabetes mellitus, hypertension and cardiovascular diseases. Duration of hemodialysis, hemodialysis adequacy, serum lipids and CaxP products were also similar among the groups. The mean CIMT value was 0.601 ± 0.107, 0.744 ± 0.139 and 0.604 ± 0.134 mm in the LN, LH and NH groups, respectively (p < 0.001). CIMT was significantly higher in LH than in the other two groups. In our study, when the three groups with similar risk factors for atherosclerosis were examined, we found that the LH group with the highest hemoglobin variability has the highest CIMT. This study is the first study to demonstrate that Hb variability is associated with an increase in CIMT in HD patients.

Reproducing the Hemoglobin Saturation Profile, a Marker of the Blood Oxygenation Level Dependent (BOLD) fMRI Effect, at the Microscopic Level.

PubMed

Hadjistassou, Constantinos; Moyle, Keri; Ventikos, Yiannis

2016-01-01

The advent of functional MRI in the mid-1990s has catalyzed progress pertaining to scientific discoveries in neuroscience. With the prospect of elucidating the physiological aspect of the Blood Oxygenation Level Dependent (BOLD) effect we present a computational capillary-tissue system capable of mapping venous hemoglobin saturation- a marker of the BOLD hemodynamic response. Free and facilitated diffusion and convection for hemoglobin and oxygen are considered in the radial and axial directions. Hemoglobin reaction kinetics are governed by the oxyhemoglobin dissociation curve. Brain activation, mimicked by dynamic transitions in cerebral blood velocity (CBv) and oxidative metabolism (CMRO2), is simulated by normalized changes in m = (ΔCBv/CBv)/(ΔCMRO2/CMRO2) of values 2, 3 and 4. Venous hemoglobin saturation profiles and peak oxygenation results, for m = 2, based upon a 50% and a 25% increase in CBv and CMRO2, respectively, lie within physiological limits exhibiting excellent correlation with the BOLD signal, for short-duration stimuli. Our analysis suggests basal CBv and CMRO2 values of 0.6 mm/s and 200 μmol/100g/min. Coupled CBv and CMRO2 responses, for m = 3 and m = 4, overestimate peak hemoglobin saturation, confirming the system's responsiveness to changes in hematocrit, CBv and CMRO2. Finally, factoring in neurovascular effects, we show that no initial dip will be observed unless there is a time delay in the onset of increased CBv relative to CMRO2.

Reproducing the Hemoglobin Saturation Profile, a Marker of the Blood Oxygenation Level Dependent (BOLD) fMRI Effect, at the Microscopic Level

PubMed Central

Hadjistassou, Constantinos; Moyle, Keri; Ventikos, Yiannis

2016-01-01

The advent of functional MRI in the mid-1990s has catalyzed progress pertaining to scientific discoveries in neuroscience. With the prospect of elucidating the physiological aspect of the Blood Oxygenation Level Dependent (BOLD) effect we present a computational capillary-tissue system capable of mapping venous hemoglobin saturation— a marker of the BOLD hemodynamic response. Free and facilitated diffusion and convection for hemoglobin and oxygen are considered in the radial and axial directions. Hemoglobin reaction kinetics are governed by the oxyhemoglobin dissociation curve. Brain activation, mimicked by dynamic transitions in cerebral blood velocity (CBv) and oxidative metabolism (CMRO2), is simulated by normalized changes in m = (ΔCBv/CBv)/(ΔCMRO2/CMRO2) of values 2, 3 and 4. Venous hemoglobin saturation profiles and peak oxygenation results, for m = 2, based upon a 50% and a 25% increase in CBv and CMRO2, respectively, lie within physiological limits exhibiting excellent correlation with the BOLD signal, for short-duration stimuli. Our analysis suggests basal CBv and CMRO2 values of 0.6 mm/s and 200 μmol/100g/min. Coupled CBv and CMRO2 responses, for m = 3 and m = 4, overestimate peak hemoglobin saturation, confirming the system’s responsiveness to changes in hematocrit, CBv and CMRO2. Finally, factoring in neurovascular effects, we show that no initial dip will be observed unless there is a time delay in the onset of increased CBv relative to CMRO2. PMID:26939128

A microfluidic approach for hemoglobin detection in whole blood

NASA Astrophysics Data System (ADS)

Taparia, Nikita; Platten, Kimsey C.; Anderson, Kristin B.; Sniadecki, Nathan J.

2017-10-01

Diagnosis of anemia relies on the detection of hemoglobin levels in a blood sample. Conventional blood analyzers are not readily available in most low-resource regions where anemia is prevalent, so detection methods that are low-cost and point-of-care are needed. Here, we present a microfluidic approach to measure hemoglobin concentration in a sample of whole blood. Unlike conventional approaches, our microfluidic approach does not require hemolysis. We detect the level of hemoglobin in a blood sample optically by illuminating the blood in a microfluidic channel at a peak wavelength of 540 nm and measuring its absorbance using a CMOS sensor coupled with a lens to magnify the image onto the detector. We compare measurements in microchannels with channel heights of 50 and 115 μm and found the channel with the 50 μm height provided a better range of detection. Since we use whole blood and not lysed blood, we fit our data to an absorption model that includes optical scattering in order to obtain a calibration curve for our system. Based on this calibration curve and data collected, we can measure hemoglobin concentration within 1 g/dL for severe cases of anemia. In addition, we measured optical density for blood flowing at a shear rate of 500 s-1 and observed it did not affect the nonlinear model. With this method, we provide an approach that uses microfluidic detection of hemoglobin levels that can be integrated with other microfluidic approaches for blood analysis.

Hematinic deficiencies and anemia statuses in antigastric parietal cell antibody-positive erosive oral lichen planus patients with desquamative gingivitis.

PubMed

Chang, Julia Yu-Fong; Wang, Yi-Ping; Wu, Yang-Che; Wu, Yu-Hsueh; Tseng, Chih-Huang; Sun, Andy

2016-10-01

Erosive oral lichen planus (EOLP) patients with desquamative gingivitis (DG) are sometimes encountered in our oral mucosal disease clinic. This study assessed hematinic deficiencies and anemia statuses in antigastric parietal cell antibody (GPCA)-positive EOLP patients with DG (GPCA + /DG + /EOLP patients). The blood hemoglobin, iron, vitamin B12, folic acid, and homocysteine concentrations and serum GPCA levels in 92 GPCA + /DG + /EOLP patients and 184 age- and sex-matched healthy controls were measured and compared between the two groups. We found that 27 (29.3%), 16 (17.4%), and 27 (29.3%) of 92 GPCA + /DG + /EOLP patients had hemoglobin (men < 13 g/dL and women < 12 g/dL), iron (< 60 μg/dL), and vitamin B12 (< 200 pg/mL) deficiencies, respectively. Moreover, 37 (40.2%) of 92 GPCA + /DG + /EOLP patients had an abnormally high blood homocysteine level (> 12.1μM). GPCA + /DG + /EOLP patients had a significantly higher frequency of hemoglobin, iron, or vitamin B12 deficiency and an abnormally high blood homocysteine level than healthy control individuals (all p < 0.001). Of 27 anemic GPCA + /DG + /EOLP patients, 13 (48.2%) had pernicious anemia, five (18.5%) had iron deficiency anemia, one (3.7%) had thalassemia trait, and the remaining eight (29.6%) had normocytic anemia. Moreover, of the 92 GPCA + /DG + /EOLP patients, 24 had macrocytosis, and only 13 (54.2%) of these 24 patients had pernicious anemia. We conclude that GPCA + /DG + /EOLP patients may have vitamin B12 deficiency, iron deficiency, and an abnormally high blood homocysteine level. In addition to pernicious anemia, GPCA + /DG + /EOLP patients may sometimes have normocytic anemia or iron deficiency anemia. Copyright © 2016. Published by Elsevier B.V.

Structure and stability of human hemoglobin microparticles prepared with a double emulsion technique.

PubMed

Cedrati, N; Bonneaux, F; Labrude, P; Maincent, P

1997-09-01

Hemoglobin solutions can be used as blood substitutes but they present some disadvantages often due to their rapid removal from the bloodstream after injection. A possible way of overcoming this problem is to trap hemoglobin inside particles. This study deals with the preparation, structure and stability of poly(lactic acid) and ethylcellulose microparticles containing human hemoglobin obtained with a double emulsion technique. We investigated the manufacturing process of these particles in order to increase the encapsulation ratio of hemoglobin. For this purpose, some parameters involved in the procedure were optimized, such as hemoglobin concentration and duration of stirring: hemoglobin loading increases with its concentration in the preparation and well-defined stirring time avoids a leakage of hemoglobin. Hemoglobin concentration, surfactant concentration i.e. poly(vinylic alcohol), amounts of polymer and solvent (methylene chloride), duration and speed of stirring. The microparticles were prepared with satisfactory yields (60 to 73%). They were spherical and their mean size was lower than 200 microns. The functional properties of entrapped hemoglobin were studied. The encapsulation did not alter hemoglobin and the oxygen affinity of the hemoglobin remained unmodified (P50 about 13.9 mm Hg in a Bis-Tris buffer pH 7.4 at 37 degrees C). Moreover, only low levels of methemoglobin could be detected (less than 3%). Besides, about 90% of encapsulated hemoglobin could be released from microparticles, with a speed related to the internal structure of the particles. The prepared microparticles were stored during one month at +4 degrees C. No degradation of the particle structure occurred and the functional properties of hemoglobin were preserved. These particles could provide a potential source of oxygen in the field of biotechnologies but any application for a transfusional purpose would first require a drastic reduction in particle size.

Partial Red Blood Cell Exchange in Children and Young Patients with Sickle Cell Disease: Manual Versus Automated Procedure.

PubMed

Escobar, Carlos; Moniz, Marta; Nunes, Pedro; Abadesso, Clara; Ferreira, Teresa; Barra, António; Lichtner, Anabela; Loureiro, Helena; Dias, Alexandra; Almeida, Helena

2017-10-31

The benefits of manual versus automated red blood cell exchange have rarely been documented and studies in young sickle cell disease patients are scarce. We aim to describe and compare our experience in these two procedures. Young patients (≤ 21 years old) who underwent manual- or automated-red blood cell exchange for prevention or treatment of sickle cell disease complications were included. Clinical, technical and hematological data were prospectively recorded and analyzed. Ninety-four red blood cell exchange sessions were performed over a period of 68 months, including 57 manual and 37 automated, 63 for chronic complications prevention, 30 for acute complications and one in the pre-operative setting. Mean decrease in sickle hemoglobin levels was higher in automated-red blood cell exchange (p < 0.001) and permitted a higher sickle hemoglobin level decrease per volume removed (p < 0.001), while hemoglobin and hematocrit remained stable. Ferritin levels on chronic patients decreased 54%. Most frequent concern was catheter outflow obstruction on manual-red blood cell exchange and access alarm on automated-red blood cell exchange. No major complication or alloimunization was recorded. Automated-red blood cell exchange decreased sickle hemoglobin levels more efficiently than manual procedure in the setting of acute and chronic complications of sickle cell disease, with minor technical concerns mainly due to vascular access. The threshold of sickle hemoglobin should be individualized for clinical and hematological goals. In our cohort of young patients, the need for an acceptable venous access was a limiting factor, but iron-overload was avoided. Automated red blood cell exchange is safe and well tolerated. It permits a higher sickle hemoglobin removal efficacy, better volume status control and iron-overload avoidance.

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

PubMed

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.

Comparison of capillary electrophoresis and high performance liquid chromatography for detection and quantification of hemoglobin New York.

PubMed

You-Qiong, Li; Hui-Ping, Huang; Zhi-Zhong, Chen; Lin, Zhao; Liang, Liang; Gui-Fang, Qin; Yun, Mo

2016-01-01

Hemoglobin (Hb) New York [β113 (G15) Val→Glu, GTG→GAG], also known as Hb Kaohsiung, is one of the most common Hb variants in South China. Currently, most used screening methods for hemoglobinopathies in South China are high performance liquid chromatography (HPLC) and capillary electrophoresis (CE). However, there is no study comparing the performance of CE and HPLC in the detection of Hb New York. In total 15 samples (including 13 adult blood samples and 2 cord blood samples) with heterozygous Hb New York were analyzed by CE and HPLC. Levels of Hb New York, HbA2, Hb, mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) were compared within the two groups. All 15 cases (100%) were detected by CE, whereas none was detected by HPLC. Mean values of Hb New York and HbA2 in adult heterozygous group were (43.82±2.47)% and (2.85±0.31)%, respectively; mean values for cord blood group were (7.95±0.78)% and (0.30±0.14)%. CE allows the detection of Hb New York, while this variant is not separated from Hb A on HPLC. CE may be the preferred method for hemoglobinopathy screening in areas with high prevalence of Hb New York.

[Study on anemia and vitamin A and vitamin D nutritional status of Chinese urban pregnant women in 2010-2012].

PubMed

Hu, Y C; Chen, J; Li, M; Wang, R; Li, W D; Yang, Y H; Yang, C; Yun, C F; Yang, L C; Yang, X G

2017-02-06

Objective: To evaluate the prevalence of anemia and the nutritional status of vitamins A and D by analyzing hemoglobin, serum retinol, and serum 25-hydroxyvitamin D levels in Chinese urban pregnant women during 2010-2012. Methods: Data were obtained from the China Nutrition and Health Survey in 2010-2012. Using multi-stage stratified sampling and population proportional stratified random sampling, 2 250 pregnant women from 34 metropolis and 41 middle-sized and small cities were included in this study. Information was collected using a questionnaire survey. The blood hemoglobin concentration was determined using the cyanmethemoglobin method, and anemia was determined using the World Health Organization guidelines combined with the elevation correction standard. The serum retinol level was determined using high-performance liquid chromatography, and vitamin A deficiency (VAD) was judged by the related standard recommended by the World Health Organization. The vitamin D level was determined using enzyme-linked immunosorbent assay and vitamin D deficiency was judged by the recommendation standards from the Institute of Medicine of The National Academies. The hemoglobin, serum retinol, and serum 25-hydroxyvitamin D levels were compared, along with differences in the prevalence of anemia, VAD, and the vitamin D deficiency rate (including deficiency and serious deficiency). Results: A total of 1 738 cases of hemoglobin level, 594 cases of serum retinol level, and 1 027 cases of serum 25-hydroxyvitamin D were available for analysis in this study. The overall blood hemoglobin level ( P (50) ( P (25)- P (75))) was 122.70 (114.00-131.10) g/L; 123.70 (115.21-132.00) g/L for metropolis and 122.01 (113.30-130.40) g/L for middle-sized and small cities. The blood hemoglobin level of metropolis residents was significantly higher than that of middle-sized and small city residents ( P= 0.027). The overall prevalence of anemia was 17.0% (295/1 738). The overall serum retinol level ( P (50) ( P (25)- P (75))) was 1.61 (1.20-2.06) μmol/L; 1.50 (1.04-2.06) μmol/L for metropolis and 1.63 (1.31-2.05) μmol/L for middle-sized and small cities. The serum retinol level of metropolis residents was significantly higher than that of middle-sized and small city residents ( P= 0.033). The overall prevalence of VAD was 7.4% (47/639); 11.5% (33/286) for metropolis and 4.0% (14/353) for middle-sized and small cities. A significant difference was observed in the prevalence of VAD between metropolis and middle-sized and small city residents ( P< 0.001). The overall serum 25-hydroxyvitamin D level ( P (50) ( P (25)- P (75))) was 15.41 (11.79-20.23) ng/ml; 14.71 (11.15-19.07) ng/ml for metropolis and 16.02 (12.65-21.36) ng/ml for middle-sized and small cities. A significant difference was observed in the vitamin D level between metropolis and middle-sized and small city residents ( P< 0.001). The overall prevalence of vitamin D deficiency was 74.3% (763/1 027); A significant difference was observed in the prevalence of serious vitamin D deficiency between metropolis (30.64%(144/470)) and middle-sized and small city residents (26%(267/1 027))( P= 0.002). There were no significant differences between blood hemoglobin level and the prevalence of anemia, VAD, and vitamin D deficiency. Conclusion: The prevalence of anemia in Chinese urban pregnant women improved from 2002 to 2012. The prevalence of vitamin D deficiency in pregnant women was generally more serious, while a certain percentage of women had VAD. The prevalence of VAD and serious vitamin D deficiency among pregnant women from metropolis was significantly higher than that of pregnant women from medium and small-sized cities.

U-shaped curve for risk associated with maternal hemoglobin, iron status, or iron supplementation.

PubMed

Dewey, Kathryn G; Oaks, Brietta M

2017-12-01

Both iron deficiency (ID) and excess can lead to impaired health status. There is substantial evidence of a U-shaped curve between the risk of adverse birth outcomes and maternal hemoglobin concentrations during pregnancy; however, it is unclear whether those relations are attributable to conditions of low and high iron status or to other mechanisms. We summarized current evidence from human studies regarding the association between birth outcomes and maternal hemoglobin concentrations or iron status. We also reviewed effects of iron supplementation on birth outcomes among women at low risk of ID and the potential mechanisms for adverse effects of high iron status during pregnancy. Overall, we confirmed a U-shaped curve for the risk of adverse birth outcomes with maternal hemoglobin concentrations, but the relations differ by trimester. For low hemoglobin concentrations, the link with adverse outcomes is more evident when hemoglobin concentrations are measured in early pregnancy. These relations generally became weaker or nonexistent when hemoglobin concentrations are measured in the second or third trimesters. Associations between high hemoglobin concentration and adverse birth outcomes are evident in all 3 trimesters but evidence is mixed. There is less evidence for the associations between maternal iron status and adverse birth outcomes. Most studies used serum ferritin (SF) concentrations as the indicator of iron status, which makes the interpretation of results challenging because SF concentrations increase in response to inflammation or infection. The effect of iron supplementation during pregnancy may depend on initial iron status. There are several mechanisms through which high iron status during pregnancy may have adverse effects on birth outcomes, including oxidative stress, increased blood viscosity, and impaired systemic response to inflammation and infection. Research is needed to understand the biological processes that underlie the U-shaped curves seen in observational studies. Reevaluation of cutoffs for hemoglobin concentrations and indicators of iron status during pregnancy is also needed. © 2017 American Society for Nutrition.

The effect of differences in altitude location of an aquaculture on fish’s hematocrit and fish’s haemoglobin of Carp fish and resistance to bacterial attack

NASA Astrophysics Data System (ADS)

Rosidah; Rizal, A.; Rustikawati, I.; Octavia, F.

2018-04-01

The aim for this research is to analyze the relation between the height place of aquaculture and life directness towards Aeromonas hydrophila attack for hematocrit and hemoglobin degrees on Cyprinus carpio L. This research have been doing on February - March 2017 at UPT PTBP Kepanjen (as Group 1), Malang (332 amsl) and UPT PBAT Umbulan IBAT as Group 2 (955 amsl). The treatment that be used is Cyprinus carpio infected by Aeromonas hydrophila. Parameters was observed, are hematocrit, hemoglobin degrees, clinical symptom of fish and the quality of water. The result of this investigation, hematocrit and hemoglobin degrees of Cyprinus carpio in level low land (Group 1, 332 amsl) around 12.8 % and 9.58 g/dL, meanwhile hematocrit and hemoglobin degrees in level up land (Group 2, 955 amsl) around 24.19 % and 12.64 g/dL. Cyprinus carpio L. after infected by Aeromonas hydrophila, it shows the clinical symptoms : its mucus be left, bleeding, its scale get peeled off and dropsy. The life directness of that Cyprinus carpio L. maintaining in 15 days 0 %. The differences between the height level of aquaculture for hematocrit and hemoglobin degrees also life directness towards Aeromonas hydrophila attack on Cyprinus carpio L.

Oxygen Measurements in Liposome Encapsulated Hemoglobin

NASA Astrophysics Data System (ADS)

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.

Reticulocyte hemoglobin equivalent as a potential marker for diagnosis of iron deficiency.

PubMed

Toki, Yasumichi; Ikuta, Katsuya; Kawahara, Yoshie; Niizeki, Noriyasu; Kon, Masayuki; Enomoto, Motoki; Tada, Yuko; Hatayama, Mayumi; Yamamoto, Masayo; Ito, Satoshi; Shindo, Motohiro; Kikuchi, Yoko; Inoue, Mitsutaka; Sato, Kazuya; Fujiya, Mikihiro; Okumura, Toshikatsu

2017-07-01

Evaluation of parameters relating to serum ferritin and iron is critically important in the diagnosis of iron deficiency anemia (IDA). The recent development of automated systems for hematology analysis has made it possible to measure reticulocyte hemoglobin equivalent (RET-He), which is thought to reflect iron content in reticulocytes, in the same sample used for complete blood count tests. If RET-He is, indeed, capable of evaluating iron deficiency (ID), it would be useful for immediate diagnosis of IDA. In the present study, we examined the usefulness of RET-He for diagnosis of ID. Blood samples were obtained from 211 patients. Anemia was defined as hemoglobin (Hb) level of <12 g/dL. Iron deficiency was defined as serum ferritin level of <12 ng/mL. Patients were classified into four groups: IDA, ID, control, and non-ID with anemia. Patients in the IDA group had significantly lower RET-He levels than those in the control group. RET-He correlated with serum ferritin in the IDA and ID groups. The area under the curve for RET-He was 0.902, indicating that RET-He facilitates the diagnosis of ID with high accuracy. RET-He changed in parallel with changes in Hb during iron administration for 21 IDA patients. Our results indicate that RET-He may be a clinically useful marker for determining ID in the general population.

Comparison of levonorgestrel-releasing intrauterine device with oral progestins in heavy menstrual bleeding (HMB) cases with uterine leiomyoma (LNG-IUD and oral progestin usage in myoma uteri).

PubMed

Tosun, Ayse Kavasoglu; Tosun, Ismet; Suer, Necdet

2014-07-01

To compare the effectiveness and acceptability of LNG-IUD with oral progesterone (norethisterone acetate; NETA) in achieving a reduction in volume of the myomas, hemoglobin levels, satisfaction of the women. This study includes randomized 30 women treated by LNG-IUD and randomized 30 women treated by oral norethisterone (NETA). All these participants in the study have received medical treatment and had been registered as patients in Istanbul Medeniyet University Göztepe Education and Research Hospital. Leiomyoma volumes and hemoglobin levels have been determined. In the third and sixth months, these measurements have been done again. We examined the adverse effects and the treatment continuity. For the statistical analysis of the findings NCSS [Number Cruncher Statistical System] 2007 & PASS 2008 program; student t, Mann Whitney U, Paired Samples t, Wilcoxon Signed Ranks, Ki-Kare, Fisher's Exact Ki-Kare tests have been used. After six months treatment, the reduction of bleeding determined by Visual Bleeding Score (VBS) in LNG-IUD group is 80% and in oral norethisteron group is 56%; in both groups leiomyoma volumes and hemoglobin levels were significantly high. LNG-IUD is a good alternative treatment to the oral progesterone in long term minimizing the hysterectomy for myoma uteri because of the good patient tolerance and easy usage.

The First Report of a 290-bp Deletion in β-Globin Gene in the South of Iran

PubMed Central

Hamid, Mohammad; Nejad, Ladan Dawoody; Shariati, Gholamreza; Galehdari, Hamid; Saberi, Alihossein; Mohammadi-Anaei, Marziye

2017-01-01

Background: β-thalassemia is one of the most widespread diseases in the world, including Iran. In this study, we reported, for the first time, a 290-bp β-globin gene deletion in the south of Iran. Methods: Four individuals from three unrelated families with Arabic ethnic background were studied in Khuzestan Province. Red blood cell indices and hemoglobin analysis were carried out according to the standard methods. Genomic DNA was obtained from peripheral blood cells by salting out procedures. β-globin gene amplification, multiplex ligation-dependent probe amplification (MLPA), and DNA sequencing were performed. Results: The PCR followed by sequencing and MLPA test of the β-globin gene confirmed the presence of a 290-bp deletion in the heterozygous form, along with -88C>A mutation. All the individuals had elevated hemoglobin A2 and normal fetal hemoglobin levels. Conclusions: This mutation causes β0-thalassemia and can be highly useful for prenatal diagnosis in compound heterozygous condition with different β-globin gene mutations. PMID:26948378

Association of Testosterone Levels With Anemia in Older Men

PubMed Central

Roy, Cindy N.; Snyder, Peter J.; Stephens-Shields, Alisa J.; Artz, Andrew S.; Bhasin, Shalender; Cohen, Harvey J.; Farrar, John T.; Gill, Thomas M.; Zeldow, Bret; Cella, David; Barrett-Connor, Elizabeth; Cauley, Jane A.; Crandall, Jill P.; Cunningham, Glenn R.; Ensrud, Kristine E.; Lewis, Cora E.; Matsumoto, Alvin M.; Molitch, Mark E.; Pahor, Marco; Swerdloff, Ronald S.; Cifelli, Denise; Hou, Xiaoling; Resnick, Susan M.; Walston, Jeremy D.; Anton, Stephen; Basaria, Shehzad; Diem, Susan J.; Wang, Christina; Schrier, Stanley L.; Ellenberg, Susan S.

2017-01-01

Importance In one-third of older men with anemia, no recognized cause can be found. Objective To determine if testosterone treatment of men 65 years or older with unequivocally low testosterone levels and unexplained anemia would increase their hemoglobin concentration. Design, Setting, and Participants A double-blinded, placebo-controlled trial with treatment allocation by minimization using 788 men 65 years or older who have average testosterone levels of less than 275 ng/dL. Of 788 participants, 126 were anemic (hemoglobin Š12.7 g/dL), 62 of whom had no known cause. The trial was conducted in 12 academic medical centers in the United States from June 2010 to June 2014. Interventions Testosterone gel, the dose adjusted to maintain the testosterone levels normal for young men, or placebo gel for 12 months. Main Outcomes and Measures The percent of men with unexplained anemia whose hemoglobin levels increased by 1.0 g/dL or more in response to testosterone compared with placebo. The statistical analysis was intent-to-treat by a logistic mixed effects model adjusted for balancing factors. Results The men had a mean age of 74.8 years and body mass index (BMI) (calculated as weight in kilograms divided by height in meters squared) of 30.7; 84.9% were white. Testosterone treatment resulted in a greater percentage of men with unexplained anemia whose month 12 hemoglobin levels had increased by 1.0 g/dL or more over baseline (54%) than did placebo (15%) (adjusted OR, 31.5; 95% CI, 3.7-277.8; P = .002) and a greater percentage of men who at month 12 were no longer anemic (58.3%) compared with placebo (22.2%) (adjusted OR, 17.0; 95% CI, 2.8-104.0; P = .002). Testosterone treatment also resulted in a greater percentage of men with anemia of known cause whose month 12 hemoglobin levels had increased by 1.0 g/dL or more (52%) than did placebo (19%) (adjusted OR, 8.2; 95% CI, 2.1-31.9; P = .003). Testosterone treatment resulted in a hemoglobin concentration of more than 17.5 g/dL in 6 men who had not been anemic at baseline. Conclusions and Relevance Among older men with low testosterone levels, testosterone treatment significantly increased the hemoglobin levels of those with unexplained anemia as well as those with anemia from known causes. These increases may be of clinical value, as suggested by the magnitude of the changes and the correction of anemia in most men, but the overall health benefits remain to be established. Measurement of testosterone levels might be considered in men 65 years or older who have unexplained anemia and symptoms of low testosterone levels. PMID:28241237

Hb Potomac (101 Glu replaced by Asp): speculations on placental oxygen transport in carriers of high-affinity hemoglobins.

PubMed

Charache, S; Jacobson, R; Brimhall, B; Murphy, E A; Hathaway, P; Winslow, R; Jones, R; Rath, C; Simkovich, J

1978-02-01

Blood from a woman with unexplained erythrocytosis had increased oxygen affinity, but no abnormality could be detected by electrophoresis or chromatography of her hemolysate. Separation of the tryptic peptides of her beta chains disclosed two half-sized peaks in the regions of beta T-11. The faster of these was abnormal, with the structure beta 101 Glu replaced by Asp. The new hemoglobin was called "Potomac." Three of the proband's four surviving siblings and both of her children were carriers. Differences in the ratio of carrier: normal children born to male of female carriers of 23 other high-affinity hemoglobins were not significant. The high proportion of carriers in this kindred was probably due to chance alone, and not because high maternal oxygen affinity interfered with oxygen transport to fetuses with normal hemoglobin.

Immunological non-response and low hemoglobin levels are predictors of incident tuberculosis among HIV-infected individuals on Truvada-based therapy in Botswana.

PubMed

Mupfumi, Lucy; Moyo, Sikhulile; Molebatsi, Kesaobaka; Thami, Prisca K; Anderson, Motswedi; Mogashoa, Tuelo; Iketleng, Thato; Makhema, Joseph; Marlink, Ric; Kasvosve, Ishmael; Essex, Max; Musonda, Rosemary M; Gaseitsiwe, Simani

2018-01-01

There is a high burden of tuberculosis (TB) in HIV antiretroviral programmes in Africa. However, few studies have looked at predictors of incident TB while on Truvada-based combination antiretroviral therapy (cART) regimens. We estimated TB incidence among individuals enrolled into an observational cohort evaluating the efficacy and tolerability of Truvada-based cART in Gaborone, Botswana between 2008 and 2011. We used Cox proportional hazards regressions to determine predictors of incident TB. Of 300 participants enrolled, 45 (15%) had a diagnosis of TB at baseline. During 428 person-years (py) of follow-up, the incidence rate of TB was 3.04/100py (95% CI, 1.69-5.06), with 60% of the cases occurring within 3 months of ART initiation. Incident cases had low baseline CD4+ T cell counts (153cells/mm3 [Q1, Q3: 82, 242]; p = 0.69) and hemoglobin levels (9.2g/dl [Q1, Q3: 8.5,10.1]; p<0.01). In univariate analysis, low BMI (HR = 0.73; 95% CI 0.58-0.91; p = 0.01) and hemoglobin levels <8 g/dl (HR = 10.84; 95%CI: 2.99-40.06; p<0.01) were risk factors for TB. Time to incident TB diagnosis was significantly reduced in patients with poor immunological recovery (p = 0.04). There was no association between baseline viral load and risk of TB (HR = 1.75; 95%CI: 0.70-4.37). Low hemoglobin levels prior to initiation of ART are significant predictors of incident tuberculosis. Therefore, there is potential utility of iron biomarkers to identify patients at risk of TB prior to initiation on ART. Furthermore, additional strategies are required for patients with poor immunological recovery to reduce excess risk of TB while on ART.

Primary structure of the hemoglobins from Sphenodon (Sphenodon punctatus, Tuatara, Rynchocephalia). Evidence for the expression of alpha D-gene.

PubMed

Abbasi, A; Wells, R M; Brittain, T; Braunitzer, G

1988-08-01

Sphenodon is the sole representative of the "beakhead" reptiles which were widely distributed during the Triassic period before the spectacular rise of dinosaurs. Sphenodon punctatus is the only survivor ("living fossil") of this period. The morphological features of Sphenodon are remarkably conservative and differ little from reptiles living 200 million years ago. In the present paper the determination of the primary structure of the tetrameric hemoglobins is described: three components are identified: hemoglobin A' (alpha A2 beta II2), hemoglobin A (alpha A2 beta I2) and hemoglobin D (alpha D2 beta II2). The components were characterized electrophoretically, the four different peptide chains were characterized by Triton electrophoresis as well as by high-performance liquid chromatography. The hemoglobins and--under dissociating conditions--also the chains, were isolated on columns of cellulose ion exchangers. Sequence determination was carried out after cleavage of the individual chains with trypsin and after a specific chemical cleavage of the Asp-Pro bond. For sequence determination the film technique and gas-phase method were employed. The data are compared with the sequence of the human hemoglobin, and interpretations of the amino-acid sequences are given. Particularly notable is the evidence of hemoglobin D: this hemoglobin (alpha D2 beta II2) is found only in birds, and in two cases in turtles. However, this component is not found in other reptiles. The results make possible an interpretation of the relatively high oxygen affinity and explain the lack of cooperativity (myoglobin properties) of these tetrameric hemoglobins.

Effect of altitude on oxygen binding by hemoglobin and on organic phosphate levels

PubMed Central

Lenfant, Claude; Torrance, John; English, Eugenia; Finch, Clement A.; Reynafarje, Cesar; Ramos, Jose; Faura, Jose

1968-01-01

The relationship between oxygen dissociation and 2,3-diphosphoglycerate (2,3-DPG) in the red cell has been studied in subjects moving from low to high altitude and vice versa. Within 24 hr following the change in altitude there was a change in hemoglobin affinity for oxygen; this modification therefore represents an important rapid adaptive mechanism to anoxia. A parallel change occurred in the organic phosphate content of the red cell. While this study does not provide direct evidence of a cause-effect relationship, the data strongly suggest that with anoxia, the observed rise in organic phosphate content of the red cell is responsible for increased availability of oxygen to tissues. Images PMID:5725278

Fibroblast Growth Factor 2-A Predictor of Outcome for Patients Irradiated for Stage II-III Non-Small-Cell Lung Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rades, Dirk, E-mail: Rades.Dirk@gmx.net; Setter, Cornelia; Dahl, Olav

2012-01-01

Purpose: The prognostic value of the tumor cell expression of the fibroblast growth factor 2 (FGF-2) in patients with non-small-cell lung cancer (NSCLC) is unclear. The present study investigated the effect of tumor cell expression of FGF-2 on the outcome of 60 patients irradiated for Stage II-III NSCLC. Methods and Materials: The effect of FGF-2 expression and 13 additional factors on locoregional control (LRC), metastasis-free survival (MFS), and overall survival (OS) were retrospectively evaluated. These additional factors included age, gender, Karnofsky performance status, histologic type, histologic grade, T and N category, American Joint Committee on Cancer stage, surgery, chemotherapy, pack-years,more » smoking during radiotherapy, and hemoglobin during radiotherapy. Locoregional failure was identified by endoscopy or computed tomography. Univariate analyses were performed with the Kaplan-Meier method and the Wilcoxon test and multivariate analyses with the Cox proportional hazard model. Results: On univariate analysis, improved LRC was associated with surgery (p = .017), greater hemoglobin levels (p = .036), and FGF-2 negativity (p <.001). On multivariate analysis of LRC, surgery (relative risk [RR], 2.44; p = .037), and FGF-2 expression (RR, 5.06; p <.001) maintained significance. On univariate analysis, improved MFS was associated with squamous cell carcinoma (p = .020), greater hemoglobin levels (p = .007), and FGF-2 negativity (p = .001). On multivariate analysis of MFS, the hemoglobin levels (RR, 2.65; p = .019) and FGF-2 expression (RR, 3.05; p = .004) were significant. On univariate analysis, improved OS was associated with a lower N category (p = .048), greater hemoglobin levels (p <.001), and FGF-2 negativity (p <.001). On multivariate analysis of OS, greater hemoglobin levels (RR, 4.62; p = .002) and FGF-2 expression (RR, 3.25; p = .002) maintained significance. Conclusions: Tumor cell expression of FGF-2 appeared to be an independent negative predictor of LRC, MFS, and OS.« less

Randomized controlled open-label trial of vitamin E-bonded polysulfone dialyzer and erythropoiesis-stimulating agent response.

PubMed

Sanaka, Tsutomu; Mochizuki, Takahiro; Kinugasa, Eriko; Kusano, Eiji; Ohwada, Shigeru; Kuno, Tsutomu; Kojima, Kenichiro; Kobayashi, Shuzo; Satoh, Minoru; Shimada, Noriaki; Nakao, Kazushi; Nakazawa, Ryoichi; Nishimura, Hideki; Noiri, Eisei; Shigematsu, Takashi; Tomo, Tadashi; Maeda, Teiryo

2013-06-01

A 1-year multicenter prospective randomized controlled study was conducted on the effects of vitamin E-bonded polysulfone dialyzers on erythropoiesis-stimulating agent response in hemodialysis patients. Major inclusion criteria were use of high-flux polysulfone dialyzers with 50-70 ml/min β2-microglobulin clearance over 3 months, transferrin saturation over 20%, same erythropoiesis-stimulating agent for over 3 months, and hemoglobin at 10-12 g/dl. Hemodialysis patients were placed in four interventional groups: two hemoglobin ranges (10.0-10.9 or 11.0-11.9 g/dl) and two dialyzers. Patients were randomly assigned by central registration to a vitamin E-bonded polysulfone dialyzers or polysulfone control group. Primary end point was relative erythropoiesis resistance index at baseline between groups at 12 months. Erythropoiesis resistance index was defined as total weekly erythropoiesis-stimulating agent dose divided by hemoglobin. There were no statistically significant differences in age or sex. There was no significant difference in relative erythropoiesis resistance index between vitamin E-bonded polysulfone dialyzers and control groups at 12 months (vitamin E-bonded polysulfone dialyzers: 1.1, control: 1.3). The vitamin E-bonded polysulfone dialyzers group showed better relative erythropoiesis resistance index than the control group at 11.0-11.9 g/dl hemoglobin (vitamin E-bonded polysulfone dialyzers: 1.0, control: 1.4 at 12 months, significant difference) but no difference at 10.0-10.9 g/dl hemoglobin. The overall relative erythropoiesis resistance index showed no difference between the vitamin E-bonded polysulfone dialyzers and control groups, although the change in relative erythropoiesis resistance index differed according to hemoglobin level.

Randomized Controlled Open-Label Trial of Vitamin E-Bonded Polysulfone Dialyzer and Erythropoiesis-Stimulating Agent Response

PubMed Central

Mochizuki, Takahiro; Kinugasa, Eriko; Kusano, Eiji; Ohwada, Shigeru; Kuno, Tsutomu; Kojima, Kenichiro; Kobayashi, Shuzo; Satoh, Minoru; Shimada, Noriaki; Nakao, Kazushi; Nakazawa, Ryoichi; Nishimura, Hideki; Noiri, Eisei; Shigematsu, Takashi; Tomo, Tadashi; Maeda, Teiryo

2013-01-01

Summary Background and objectives A 1-year multicenter prospective randomized controlled study was conducted on the effects of vitamin E-bonded polysulfone dialyzers on erythropoiesis-stimulating agent response in hemodialysis patients. Design, setting, participants, & measurements Major inclusion criteria were use of high-flux polysulfone dialyzers with 50–70 ml/min β2-microglobulin clearance over 3 months, transferrin saturation over 20%, same erythropoiesis-stimulating agent for over 3 months, and hemoglobin at 10–12 g/dl. Hemodialysis patients were placed in four interventional groups: two hemoglobin ranges (10.0–10.9 or 11.0–11.9 g/dl) and two dialyzers. Patients were randomly assigned by central registration to a vitamin E-bonded polysulfone dialyzers or polysulfone control group. Primary end point was relative erythropoiesis resistance index at baseline between groups at 12 months. Erythropoiesis resistance index was defined as total weekly erythropoiesis-stimulating agent dose divided by hemoglobin. Results There were no statistically significant differences in age or sex. There was no significant difference in relative erythropoiesis resistance index between vitamin E-bonded polysulfone dialyzers and control groups at 12 months (vitamin E-bonded polysulfone dialyzers: 1.1, control: 1.3). The vitamin E-bonded polysulfone dialyzers group showed better relative erythropoiesis resistance index than the control group at 11.0–11.9 g/dl hemoglobin (vitamin E-bonded polysulfone dialyzers: 1.0, control: 1.4 at 12 months, significant difference) but no difference at 10.0–10.9 g/dl hemoglobin. Conclusions The overall relative erythropoiesis resistance index showed no difference between the vitamin E-bonded polysulfone dialyzers and control groups, although the change in relative erythropoiesis resistance index differed according to hemoglobin level. PMID:23599410

The influence of socioeconomic status on the hemoglobin level and anthropometry of sickle cell anemia patients in steady state at the Lagos University Teaching Hospital.

PubMed

Animasahun, B A; Temiye, E O; Ogunkunle, O O; Izuora, A N; Njokanma, O F

2011-01-01

Sickle cell anemia (SCA) has multisystemic manifestations and is associated with severe morbidity and high mortality. It commonly affects growth leading to wasting and stunting. This study aimed to determine the influence of socioeconomic status on the nutritional status using anthropometric measurements and steady-state hemoglobin, of children with homozygous SCA, aged 1 year to 10 years in steady state at the Lagos University Teaching Hospital. This is a cross-sectional study involving 100 children with SCA and 100 age-, sex-, and social class-matched controls that fulfilled the inclusion criteria. Social class was assessed using educational attainment and occupation of parents. Hemoglobin concentration was determined using the oxy-hemoglobin method. This study demonstrated a significantly lower mean weight and weight-for-height in the SCA patients than those of controls (P < 0.001). By contrast, this study did not demonstrate any statistical significant difference in the mean height and mean body mass index of SCA patients and controls (P = 0.06) and (P = 0.12), respectively. The mean weight, height, and body mass indices of the subjects and controls were consistently below those of the NCHS standards. The magnitude of the difference from the NCHS standard was also more pronounced in the subjects, increased with advancing age and affected male subjects more than females. Progressive declines in the anthropometric attainment and hemoglobin concentration were observed from social class 1 to 4; this was statistically significant in controls (P = 0.00) but not in subjects (P > 0.1). However, SCA patients had significantly lower values than controls in each of the social classes. Poor socioeconomic status has an adverse effect on the nutritional status and hemoglobin of SCA patients.

Enhancement of welan gum production in Sphingomonas sp. HT-1 via heterologous expression of Vitreoscilla hemoglobin gene.

PubMed

Liu, Xiaoliu; Zhu, Ping; Jiang, Ruifan; Wu, Lingtian; Feng, Xiaohai; Li, Sha; Xu, Hong

2017-01-20

Welan gum is a microbial polysaccharide produced by Sphingomonas sp. Its production is limited by the dissolved oxygen levels in the highly viscous fermentation. A strategy of heterologous expression of the Vitreoscilla hemoglobin gene in Sphingomonas sp. HT-1 was investigated to alleviate oxygen limitation and improve the yield of welan gum. Ultimately, the welan gum production increased from 25.3g/L to 34.6g/L, whereas the rheological behavior of welan gum solutions remained virtually unchanged. The transcriptional levels of the key genes in the electron transfer chain, TCA cycle and welan gum synthesis pathway, as well as ATP level revealed that the VHb expression in Sphingomonas sp. HT-1 enhanced welan gum biosynthesis by improving respiration and ATP supply. This study would pave the genetic manipulation way for enhancing welan gum yield, and it's also of great importance for the industrial applications of welan gum under harsh conditions. Copyright © 2016 Elsevier Ltd. All rights reserved.

Active Brazilian crack cocaine users: nutritional, anthropometric, and drug use profiles.

PubMed

Escobar, Mariana; Scherer, Juliana N; Soares, Cassia M; Guimarães, Luciano S P; Hagen, Martine E; von Diemen, Lisia; Pechansky, Flavio

2018-02-15

To evaluate the nutritional status of crack users and to analyze its correlation with drug use profiles. Cross-sectional study with 108 crack users. Anthropometric data were assessed through body mass index (BMI) and bioimpedance (BIA) measurements. A blood test to analyze hematocrit, hemoglobin, glucose, and lipid profiles was also performed. Crack use was determined through a standardized interview. Based on BMI and BIA, most individuals were eutrophic (about 70%). Regarding hematological parameters, we found that hemoglobin and hematocrit levels were below normal for 32.4 and 30.6% of patients, respectively. Considering normal parameters, a large part of the sample (60.2%) had low levels of HDL cholesterol and high levels of triglycerides (38%). There were no significant correlations between drug profile and nutritional variables. This is a pioneering study that examines the nutritional status of crack users. Our results showed that most crack users present normal anthropometric findings and the prevalence of underweight is low. However, blood analysis showed changes and a specific type of malnutrition.

Erythrocyte isozymes of phosphofructokinase in genetically high- and low-2,3-diphosphoglycerate rats.

PubMed

Noble, N A; Kuwashima, L H; Togioka, T T; Tanaka, K R

1982-12-01

A major locus (Dpg) with two alleles (d and D) controls erythrocyte 2,3-diphosphoglycerate (DPG) levels in Long-Evans rats and is closely linked to a locus (Hbb) determining a hemoglobin electrophoretic polymorphism. Glycolytic intermediate levels and phosphofructokinase (PFK) kinetic studies suggest that in vivo PFK activity differences underlie the differences in DPG levels. We report here chromatographic and immunologic evidence that rat erythrocyte PFK is composed of two isozymes which elute from DEAE-Sephadex at positions identical to those of the isozymes in platelets and liver, respectively. The percentage of platelet-type PFK is significantly (P less than 0.05) smaller in low-DPG (dd) hemolysates than in DD hemolysates regardless of hemoglobin phenotype. When hemolysates were prepared in a stabilizing buffer, PFK specific activity was significantly (P less than 0.005) higher in DD rats. These data suggest that the PFK kinetic differences may result from alterations in the isozyme composition of active PFK.

Alteration of the α1β2/α2β1 subunit interface contributes to the increased hemoglobin-oxygen affinity of high-altitude deer mice

PubMed Central

Inoguchi, Noriko; Mizuno, Nobuhiro; Baba, Seiki; Kumasaka, Takashi; Natarajan, Chandrasekhar; Storz, Jay F.

2017-01-01

Background Deer mice (Peromyscus maniculatus) that are native to high altitudes in the Rocky Mountains have evolved hemoglobins with an increased oxygen-binding affinity relative to those of lowland conspecifics. To elucidate the molecular mechanisms responsible for the evolved increase in hemoglobin-oxygen affinity, the crystal structure of the highland hemoglobin variant was solved and compared with the previously reported structure for the lowland variant. Results Highland hemoglobin yielded at least two crystal types, in which the longest axes were 507 and 230 Å. Using the smaller unit cell crystal, the structure was solved at 2.2 Å resolution. The asymmetric unit contained two tetrameric hemoglobin molecules. Conclusions The analyses revealed that αPro50 in the highland hemoglobin variant promoted a stable interaction between αHis45 and heme that was not seen in the αHis50 lowland variant. The αPro50 mutation also altered the nature of atomic contacts at the α1β2/α2β1 intersubunit interfaces. These results demonstrate how affinity-altering changes in intersubunit interactions can be produced by mutations at structurally remote sites. PMID:28362841

Alteration of the α1β2/α2β1 subunit interface contributes to the increased hemoglobin-oxygen affinity of high-altitude deer mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Inoguchi, Noriko; Mizuno, Nobuhiro; Baba, Seiki

2017-03-31

Deer mice (Peromyscus maniculatus) that are native to high altitudes in the Rocky Mountains have evolved hemoglobins with an increased oxygen-binding affinity relative to those of lowland conspecifics. To elucidate the molecular mechanisms responsible for the evolved increase in hemoglobin-oxygen affinity, the crystal structure of the highland hemoglobin variant was solved and compared with the previously reported structure for the lowland variant. Highland hemoglobin yielded at least two crystal types, in which the longest axes were 507 and 230 Å. Using the smaller unit cell crystal, the structure was solved at 2.2 Å resolution. The asymmetric unit contained two tetramericmore » hemoglobin molecules. The analyses revealed that αPro50 in the highland hemoglobin variant promoted a stable interaction between αHis45 and heme that was not seen in the αHis50 lowland variant. The αPro50 mutation also altered the nature of atomic contacts at the α1β2/α2β1 intersubunit interfaces. These results demonstrate how affinity-altering changes in intersubunit interactions can be produced by mutations at structurally remote sites.« less

A coordination polymer based magnetic adsorbent material for hemoglobin isolation from human whole blood, highly selective and recoverable

NASA Astrophysics Data System (ADS)

Zhang, Xiaoxing; Tan, Jipeng; Xu, Xinxin; Shi, Fanian; Li, Guanglu; Yang, Yiqiao

2017-09-01

A composite material has been obtained successfully through the loading of nanoscale coordination polymer on magnetic Fe3O4@SiO2 core-shell particle. In this composite material, coordination polymer nanoparticles distribute uniformly on Fe3O4@SiO2 and these two components are "tied" together firmly with chemical bonds. Adsorption experiments suggest this composite material exhibits very excellent selectivity to hemoglobin. But under the same condition, its adsorption to bovine serum albumin can almost be ignored. This selectivity can be attributed to the existence of hydrophobic interactions between coordination polymer nanoparticle and hemoglobin. For composite material, the hemoglobin adsorption process follows Langmuir model perfectly with high speed. The adsorbed hemoglobin can be eluted easily by sodium dodecyl sulfate stripping reagent with structure and biological activity of hemoglobin keeps well. The composite material was also employed to separate hemoglobin from human whole blood, which receives a very satisfactory result. Furthermore, magnetic measurement reveals ferromagnetic character of this composite material with magnetization saturation 3.56 emu g-1 and this guarantees its excellent magnetic separation performance from the treated solution.

Early childhood hemoglobin level is a strong predictor of hemoglobin levels during later childhood among low-income Alaska children.

PubMed

Gessner, Bradford D

2009-12-01

For unknown reasons, Arctic Indigenous children have iron deficiency and anemia prevalences up to 10 times higher than national reference populations. The current study sought to identify the importance of Alaska Native status, residence and hemoglobin (Hb) level at age 10 to 23 months for predicting Hb levels at age 24 to 59 months when controlling for potential confounders. Retrospective cohort. A birth certificate database was linked to a database containing hemoglobin levels determined through the U.S. Supplemental Nutrition Program for Women, Infants and Children (WIC) among Alaskan children age 10 to 59 months evaluated from 1999-2006. Of children with a birth certificate matched to WIC data, Alaska Native status and residence in western and northern Alaska were associated strongly with anemia at both ages. Nevertheless, of 5,796 children with Hb levels determined at both ages, the single strongest predictor of Hb level at age 24 to 59 months was Hb level at age 10 to 23 months. The community-level anemia prevalence among children age 10 to 23 months was predictive of community-level anemia prevalence among children age 24 to 59 months. The early onset of anemia and the strong association between earlier and later Hb levels or anemia at both the individual and community levels suggest a role for prenatal effects that remain until at least age 5 years. This is true particularly of Yupik and Inupiat children, who make up the primary residents of western and northern Alaska.

The Hemoglobin E Thalassemias

PubMed Central

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

Monoclonal antibodies to human hemoglobin S and cell lines for the production thereof

DOEpatents

Jensen, Ronald H.; Vanderlaan, Martin; Bigbee, William L.; Stanker, Larry H.; Branscomb, Elbert W.; Grabske, Robert J.

1988-01-01

The present invention provides monoclonal antibodies specific to and distinguish between hemoglobin S and hemoglobin A and methods for their production and use. These antibodies are capable of distinguishing between two hemoglobin types which differ from each other by only a single amino acid residue. The antibodies produced according to the present method are useful as immunofluorescent markers to enumerate circulating red blood cells which have the property of altered expression of the hemoglobin gene due to somatic mutation in stem cells. Such a measurement is contemplated as an assay for in vivo cellular somatic mutations in humans. Since the monoclonal antibodies produced in accordance with the instant invention exhibit a high degree of specificity to and greater affinity for hemoglobin S, they are suitable for labeling human red blood cells for flow cytometric detection of hemoglobin genotype.

Perioperative factors associated with pressure ulcer development after major surgery.

PubMed

Kim, Jeong Min; Lee, Hyunjeong; Ha, Taehoon; Na, Sungwon

2018-02-01

Postoperative pressure ulcers are important indicators of perioperative care quality, and are serious and expensive complications during critical care. This study aimed to identify perioperative risk factors for postoperative pressure ulcers. This retrospective case-control study evaluated 2,498 patients who underwent major surgery. Forty-three patients developed postoperative pressure ulcers and were matched to 86 control patients based on age, sex, surgery, and comorbidities. The pressure ulcer group had lower baseline hemoglobin and albumin levels, compared to the control group. The pressure ulcer group also had higher values for lactate levels, blood loss, and number of packed red blood cell ( p RBC) units. Univariate analysis revealed that pressure ulcer development was associated with preoperative hemoglobin levels, albumin levels, lactate levels, intraoperative blood loss, number of p RBC units, Acute Physiologic and Chronic Health Evaluation II score, Braden scale score, postoperative ventilator care, and patient restraint. In the multiple logistic regression analysis, only preoperative low albumin levels (odds ratio [OR]: 0.21, 95% CI: 0.05-0.82; P < 0.05) and high lactate levels (OR: 1.70, 95% CI: 1.07-2.71; P < 0.05) were independently associated with pressure ulcer development. A receiver operating characteristic curve was used to assess the predictive power of the logistic regression model, and the area under the curve was 0.88 (95% CI: 0.79-0.97; P < 0.001). The present study revealed that preoperative low albumin levels and high lactate levels were significantly associated with pressure ulcer development after surgery.

Using the effects of maternal nutritional indicators (hemoglobin and total protein) on baby's birth weight outcome to forecast a paradigm shift toward increased levels of non-communicable diseases in children.

PubMed

Ahmadu, Baba Usman; Yakubu, Nyandaiti; Yusuph, Haruna; Alfred, Marshall; Bazza, Buba; Lamurde, Abdullahi Suleiman

2013-01-01

Maternal malnutrition can lead to low birth weight in babies, which puts them at risk of developing non-communicable diseases later in life. Evidence from developed countries has shown that low birth weight is associated with a predisposition to higher rates of non-communicable diseases later in life. However, information on this is lacking in developing countries. Thus, this work studied the effects of maternal nutritional indicators (hemoglobin and total protein) on birth weight outcome of babies to forecast a paradigm shift toward increased levels of non-communicable diseases in children. Mother-baby pairs were enrolled in this study using systematic random sampling. Maternal haemogblobin and total proteins were measured using micro-hematocrit and biuret methods, and birth weights of their babies were estimated using the bassinet weighing scale. Of the 168 (100%) babies that participated in this study, 122 (72.6%) were delivered at term and 142 (84.5%) had normal birth weights. Mean comparison of baby's birth weight and maternal hemoglobin was not significant (P = 0.483), that for maternal total protein was also not significant (P = 0.411). Even though positive correlation coefficients were observed between birth weight of babies, maternal hemoglobin and total proteins, these were however not significant. Maternal nutrition did not contribute significantly to low birth weight in our babies. Therefore, association between maternal nutrition and low birth weight to predict future development of non-communicable diseases in our study group is highly unlikely. However, we recommend further work.

Allosteric properties of hemoglobin and the plasma membrane of the erythrocyte: new insights in gas transport and metabolic modulation.

PubMed

De Rosa, Maria Cristina; Carelli Alinovi, Cristiana; Galtieri, Antonio; Russo, Annamaria; Giardina, Bruno

2008-02-01

Within the red blood cell the hemoglobin molecule is subjected to modulation mechanisms, namely homo- and heterotropic interactions, which optimize its functional behavior to the specific physiological requirements. At the cellular level, these modulation mechanisms are utilized to perform a number of other functions that are not minor with respect to the basic function of oxygen transport. Here we report some key examples concerning: (i) the interaction of hemoglobin with band 3 and its influence on glucose metabolism; (ii) the role of the ligand-linked quaternary transition of hemoglobin in the control of "NO bioactivity" and of gas diffusion; (iii) the interaction of plasma membrane with the various oxidative derivatives of the hemoglobin molecule. (c) 2008 IUBMB.

Type 2 Diabetes and Spina Bifida

MedlinePlus

... c-peptide; and fasting lipid panel. • Hemoglobin A1C test which indicates the body’s long term control of blood sugar Hemoglobin Levels Normal = less than 5.7% Pre-Diabetes = 5.7% – 6.4% Diabetes = 6.5% ...

Muscle Oxygen Supply Impairment during Exercise in Poorly Controlled Type 1 Diabetes

PubMed Central

TAGOUGUI, SEMAH; LECLAIR, ERWAN; FONTAINE, PIERRE; MATRAN, RÉGIS; MARAIS, GAELLE; AUCOUTURIER, JULIEN; DESCATOIRE, AURÉLIEN; VAMBERGUE, ANNE; OUSSAIDENE, KAHINA; BAQUET, GEORGES; HEYMAN, ELSA

2015-01-01

ABSTRACT Purpose Aerobic fitness, as reflected by maximal oxygen (O2) uptake (V˙O2max), is impaired in poorly controlled patients with type 1 diabetes. The mechanisms underlying this impairment remain to be explored. This study sought to investigate whether type 1 diabetes and high levels of glycated hemoglobin (HbA1c) influence O2 supply including O2 delivery and release to active muscles during maximal exercise. Methods Two groups of patients with uncomplicated type 1 diabetes (T1D-A, n = 11, with adequate glycemic control, HbA1c <7.0%; T1D-I, n = 12 with inadequate glycemic control, HbA1c >8%) were compared with healthy controls (CON-A, n = 11; CON-I, n = 12, respectively) matched for physical activity and body composition. Subjects performed exhaustive incremental exercise to determine V˙O2max. Throughout the exercise, near-infrared spectroscopy allowed investigation of changes in oxyhemoglobin, deoxyhemoglobin, and total hemoglobin in the vastus lateralis. Venous and arterialized capillary blood was sampled during exercise to assess arterial O2 transport and factors able to shift the oxyhemoglobin dissociation curve. Results Arterial O2 content was comparable between groups. However, changes in total hemoglobin (i.e., muscle blood volume) was significantly lower in T1D-I compared with that in CON-I. T1D-I also had impaired changes in deoxyhemoglobin levels and increase during high-intensity exercise despite normal erythrocyte 2,3-diphosphoglycerate levels. Finally, V˙O2max was lower in T1D-I compared with that in CON-I. No differences were observed between T1D-A and CON-A. Conclusions Poorly controlled patients displayed lower V˙O2max and blunted muscle deoxyhemoglobin increase. The latter supports the hypotheses of increase in O2 affinity induced by hemoglobin glycation and/or of a disturbed balance between nutritive and nonnutritive muscle blood flow. Furthermore, reduced exercise muscle blood volume in poorly controlled patients may warn clinicians of microvascular dysfunction occurring even before overt microangiopathy. PMID:24983346

Exenatide's effect in reducing weight and glycosylated hemoglobin level in an Arab population with type 2 diabetes.

PubMed

Bashier, Alaaeldin M; Abdelgadir, Elamin I; Khalifa, Azza A; Rashid, Fouzia; Abuelkeir, Sona M; Bachet, Fawzi E

2014-11-01

To determine whether exenatide is effective in reducing weight and glycosylated hemoglobin level (HbA1c), and to investigate its efficacy in improving lipid profile, blood pressure, and creatinine levels in the Arab population. This study was conducted at the Endocrine Unit, Dubai Hospital, Dubai, United Arab Emirates. We retrospectively collected data from patients with type 2 diabetes started on exenatide between November 2011 and February 2012. Data included demographics, clinical, laboratory results, and medications used. A general linear model adjusted by baseline characteristics (weight, HbA1C, age, use of statins, and duration of diabetes) was used to assess changes between baseline and end of trial in HbA1C, weight, low density lipoprotein cholesterol, total cholesterol, triglycerides, creatinine, and blood pressure. After 6 months of treatment with exenatide, the HbA1c decreased by 0.47% (95% confidence level [CI]: -0.01 - 0.95) (p=0.055). Weight reduction was highly significant; 5.6 kg (95% CI: 3.34 - 7.85) (p<0.001). Those reductions remained significant after adjustment for confounding factors. This study showed that weight reduction was highly significant with exenatide. The borderline significance in HbA1c reduction can be attributed to the small sample size. 

Acrylamide exposure measured by food frequency questionnaire and hemoglobin adduct levels and prostate cancer risk in the Cancer of the Prostate in Sweden Study

PubMed Central

Wilson, Kathryn M.; Bälter, Katarina; Adami, Hans-Olov; Grönberg, Henrik; Vikström, Anna C.; Paulsson, Birgit; Törnqvist, Margareta; Mucci, Lorelei A.

2010-01-01

Acrylamide, a probable human carcinogen, is formed during the cooking of many commonly consumed foods. Data are scant on whether dietary acrylamide represents an important cancer risk in humans. We studied the association between acrylamide and prostate cancer risk using two measures of acrylamide exposure: intake from a food frequency questionnaire (FFQ) and acrylamide adducts to hemoglobin. We also studied the correlation between these two exposure measures. We used data from the population-based case-control study Cancer of the Prostate in Sweden (CAPS). Dietary data was available for 1499 cases and 1118 controls. Hemoglobin adducts of acrylamide were measured in blood samples from a subset of 170 cases and 161 controls. We calculated odds ratios (ORs) for the risk of prostate cancer in high versus low quantiles of acrylamide exposure using logistic regression. The correlation between FFQ acrylamide intake and acrylamide adducts in non-smokers was 0.25 (95% confidence interval: 0.14–0.35), adjusted for age, region, energy intake, and laboratory batch. Among controls the correlation was 0.35 (95% CI: 0.21–0.48); among cases it was 0.15 (95% CI: 0.00–0.30). The OR of prostate cancer for the highest versus lowest quartile of acrylamide adducts was 0.93 (95% CI: 0.47–1.85, p-value for trend=0.98). For FFQ acrylamide, the OR of prostate cancer for the highest versus lowest quintile was 0.97 (95% CI: 0.75–1.27, p trend=0.67). No significant associations were found between acrylamide exposure and risk of prostate cancer by stage, grade, or PSA level. Acrylamide adducts to hemoglobin and FFQ-measured acrylamide intake were moderately correlated. Neither measure of acrylamide exposure – hemoglobin adducts or FFQ – was associated with risk of prostate cancer. PMID:19142870

Measurements of coherent hemodynamics to enrich the physiological information provided by near-infrared spectroscopy (NIRS) and functional MRI

NASA Astrophysics Data System (ADS)

Sassaroli, Angelo; Tgavalekos, Kristen; Pham, Thao; Krishnamurthy, Nishanth; Fantini, Sergio

2018-02-01

Hemodynamic-based neuroimaging techniques such as functional magnetic resonance imaging (fMRI) and near-infrared spectroscopy (NIRS) sense hemoglobin concentration in cerebral tissue. The local concentration of hemoglobin, which is differentiated into oxy- and deoxy-hemoglobin by NIRS, features spontaneous oscillations over time scales of 10-100 s in response to a number of local and systemic physiological processes. If one of such processes becomes the dominant source of cerebral hemodynamics, there is a high coherence between this process and the associated hemodynamics. In this work, we report a method to identify such conditions of coherent hemodynamics, which may be exploited to study and quantify microvasculature and microcirculation properties. We discuss how a critical value of significant coherence may depend on the specific data collection scheme (for example, the total acquisition time) and the nature of the hemodynamic data (in particular, oxy- and deoxy-hemoglobin concentrations measured with NIRS show an intrinsic level of correlation that must be taken into account). A frequency-resolved study of coherent hemodynamics is the basis for the new technique of coherent hemodynamics spectroscopy (CHS), which aims to provide measures of cerebral blood flow and cerebral autoregulation. While these concepts apply in principle to both fMRI and NIRS data, in this article we focus on NIRS data.

Predictors of change in nutritional and hemoglobin status among adults treated for tuberculosis in Tanzania.

PubMed

Kawai, K; Villamor, E; Mugusi, F M; Saathoff, E; Urassa, W; Bosch, R J; Spiegelman, D; Fawzi, W W

2011-10-01

Patients with tuberculosis (TB) often suffer from profound malnutrition. To examine the patterns and predictors of change in nutritional and hemoglobin status during and after TB treatment. A total of 471 human immunodeficiency virus (HIV) positive and 416 HIV-negative adults with pulmonary TB were prospectively followed in Dar es Salaam, Tanzania. All patients received 8 months' TB treatment following enrollment. About 40% of HIV-positive and 47% of HIV-negative TB patients had body mass index (BMI) < 18.5 kg/m 2 at baseline, while about 94% of HIV-positive and 84% of HIV-negative participants were anemic at baseline. Both HIV-positive and HIV-negative patients experienced increases in BMI and hemoglobin concentrations over the course of TB treatment. Among HIV- positive patients, older age, low CD4 cell counts, and high viral load were independently associated with a smaller increase in BMI from baseline to 8 months. Fe- male sex, older age, low CD4 cell counts, previous TB infection and less money spent on food were independently associated with a smaller improvement in hemoglobin levels among HIV-positive patients during treatment. HIV-positive TB patients, especially those with low CD4 cell counts, showed poor nutritional recovery during TB treatment. Adequate nutritional support should be considered during TB treatment.

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

PubMed Central

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

Antidiabetic Activity of Aqueous Leaves Extract of Sesbania sesban (L) Merr. in Streptozotocin Induced Diabetic Rats

PubMed Central

Pandhare, Ramdas B.; Sangameswaran, B.; Mohite, Popat B.; Khanage, Shantaram G.

2011-01-01

The aqueous leaves extract of Sesbania sesban (L) Merr. (Family: Fabaceae) was evaluated for its antidiabetic potential on normal and streptozotocin (STZ)-induced diabetic rats. In the chronic model, the aqueous extract was administered to normal and STZ- induced diabetic rats at the doses of 250 and 500 mg/kg body weight (b.w.) p.o. per day for 30 days. The fasting Blood Glucose Levels (BGL), serum insulin level and biochemical data such as glycosylated hemoglobin, Total Cholesterol (TC), Triglycerides (TG), High Density Lipoproteins (HDL) and Low Density Lipoproteins (LDL) were evaluated and all were compared to that of the known anti-diabetic drug glibenclamide (0.25 mg/kg b.w.). The statistical data indicated significant increase in the body weight, liver glycogen, serum insulin and HDL levels and decrease in blood glucose, glycosylated hemoglobin, total cholesterol and serum triglycerides when compared with glibenclamide. Thus the aqueous leaves extract of Sesbania sesban had beneficial effects in reducing the elevated blood glucose level and lipid profile of STZ-induced diabetic rats. PMID:23407749

The fate of phenylhydroxylamine in human red cells.

PubMed

Kiese, M; Taeger, K

1976-01-01

Phenylhydroxylamine added to human red cells under aerobic conditions and in the presence of glucose was partly reduced to aniline. About half the hydroxylamine was recovered as amine after a 2-hr incubation. The aniline, after acetylation, was identified as acetanilide by melting point, Rf-value in TCL as well as UV, IR, and NMR spectroscopy. The fate of the remaining phenylhydroxylamine was followed by use of 14C-labeled phenylhydroxylamine. About 30% of the total radioactivity was bound to hemoglobin or other proteins and about 20% was found in highly polar low-molecular substances which were insoluble in organic solvents. The elucidation of the sites at which phenylhydroxylamine was bound to hemoglobin was complicated by the lability of the bonds. When purified human hemoglobin had reacted with radioactive phenylhydroxylamine, large proportions of the radioactivity bound to hemoglobin were removed by treatment with acid or with PMB for separation of alpha- and beta-chains. The radioactive compound liberated from hemoglobin by acid was found to be aniline. After reaction with phenylhydroxylamine the number of SH groups titrable with PMB was found to be diminished. Pretreatment of hemoglobin with N-ethylmaleimide or PMB decreased the amount of phenylhydroxylamine bound to hemoglobin but did not fully prevent the reaction. Tryptic digestion of hemoglobin after reaction with radioactive phenylhydroxylamine yielded tryptic peptides with lower specific activity than that of hemoglobin. Chymotryptic digestion of the tryptic core yielded a core with specific activity much higher than that of hemoglobin. Fingerprinting of the tryptic or chymotryptic hydrolyzates showed the presence of peptides with high and other ones with low or no radioactivity and of radioactive compounds which did not react with ninhydrin. In the covalent binding of phenylhydroxylamine to globin the SH group beta93 plays an important role, but other yet unknown sites are also reactive.

Vitamin D and glycemic control in diabetes mellitus type 2.

PubMed

Kostoglou-Athanassiou, Ifigenia; Athanassiou, Panagiotis; Gkountouvas, Anastasios; Kaldrymides, Philippos

2013-08-01

The extraskeletal effects of vitamin D have attracted considerable interest. Vitamin D deficiency appears to be related to the development of diabetes mellitus type 2 and the metabolic syndrome. Vitamin D may affect glucose homeostasis, vitamin D levels having been found to be inversely related to glycosylated hemoglobin levels in gestational diabetes mellitus. In addition, vitamin D appears to protect from the development of gestational diabetes mellitus. The aim was to study levels of 25-hydroxy vitamin D3 [25(OH)D3] and the relationship between 25(OH)D3 levels and glycemic control in patients with diabetes mellitus type 2. Glycosylated hemoglobin (HbA1c) and 25(OH)D3 levels were measured in a group of 120 diabetes mellitus type 2 patients. The same measurements were performed in a group of 120 control subjects of the same age and sex. 25(OH)D3 was measured by radioimmunoassay and glycosylated hemoglobin (HbA1c) was measured by high-performance liquid chromatography. 25(OH)D3 levels were lower in the diabetes mellitus type 2 patients than in the control group, being 19.26 ± 0.95 ng/ml and 25.49 ± 1.02 ng/ml, in the patient and control groups, respectively (p < 0.001, Student's t-test). 25(OH)D3 levels were found to be inversely associated with HbA1c levels in the diabetic patients (p = 0.008, r (2) = 0.058, linear regression). 25(OH)D3 levels were found to be inversely associated with HbA1c when the patient and control groups were analysed together (p < 0.001, r (2) = 0.086). Vitamin D levels appeared to be lower in diabetes mellitus type 2 patients than in the control group, vitamin D levels being related to glycemic control in diabetes mellitus type 2. These findings may have therapeutic implications as cautious vitamin D supplementation may improve glycemic control in diabetes mellitus type 2.

Fetal hemoglobin in sickle cell anemia: a glass half full?

PubMed

Steinberg, Martin H; Chui, David H K; Dover, George J; Sebastiani, Paola; Alsultan, Abdulrahman

2014-01-23

Fetal hemoglobin (HbF) modulates the phenotype of sickle cell anemia by inhibiting deoxy sickle hemoglobin (HbS) polymerization. The blood concentration of HbF, or the number of cells with detectable HbF (F-cells), does not measure the amount of HbF/F-cell. Even patients with high HbF can have severe disease because HbF is unevenly distributed among F-cells, and some cells might have insufficient concentrations to inhibit HbS polymerization. With mean HbF levels of 5%, 10%, 20%, and 30%, the distribution of HbF/F-cell can greatly vary, even if the mean is constant. For example, with 20% HbF, as few as 1% and as many as 24% of cells can have polymer-inhibiting, or protective, levels of HbF of ∼10 pg; with lower HbF, few or no protected cells can be present. Only when the total HbF concentration is near 30% is it possible for the number of protected cells to approach 70%. Rather than the total number of F-cells or the concentration of HbF in the hemolysate, HbF/F-cell and the proportion of F-cells that have enough HbF to thwart HbS polymerization is the most critical predictor of the likelihood of severe sickle cell disease.

Hemoglobin oxygen affinty in patients with low-output heart failure and cardiogenic shock after acute myocardial infaraction.

PubMed

Agostoni, A; Lotto, A; Stabilini, R; Bernasconi, C; Gerli, G; Gattinoni, L; Lapichino, G; Sslvadé, P

1975-06-01

The aim of this study was to determine the oxigen affinity actually present in vivo in blood from patients with acute myocardial infarction. Patients with uncomplicated acute myocardial infarction had normal value of P50 in vivo (partial pressure of oxygen at which 50 percent of the hemoglobin is saturated with oxygen at fixed levels of pHand PC02 present in vivo). Also the values of P50 in vivo of blood from patients with low cardiac output with mild or severe heart failured did not differ from the normal mean. This was the consequence of an increase of 2, 3-diphosphoglycerate levels (which reduces the oxygen affinity of hemoglobin) and of the immediate effect of alkalosis (Bohr effect). By contrast, the values of P50 in vivo were significantly increased in patients with cardiogenic shock. This could be ascribed to the state of acute acidiosis present in these patients. In these conditions the changes in the values of P50 in vivo play an important role in the oxygen delivery to the tissues. However, high values of P50 do not enhance oxygen delivery when a severe arterial hypoxemia (P02 smaller than 40-45 mm Hg) is also present.

42 CFR 494.90 - Condition: Patient plan of care.

Code of Federal Regulations, 2010 CFR

2010-10-01

...-based professionally-accepted clinical nutrition indicators may be monitored, as appropriate. (3... achieve and sustain the clinically appropriate hemoglobin/hematocrit level. The patient's hemoglobin... is a change in transplant candidate status. (d) Standard: Patient education and training. The patient...

Tranexamic acid administration to older patients undergoing primary total hip arthroplasty conserves hemoglobin and reduces blood loss

PubMed Central

Lubberdink, Ashley; Clements, Nigel; Dihllon, Kiran; Sharma, Vicky

2018-01-01

Background Tranexamic acid effects in older people are difficult to predict. This study investigated the following research questions: 1) Is tranexamic acid effective in older patients undergoing primary total hip arthroplasty (THA)? and 2) Is there a difference in the effect of tranexamic acid between younger and older patients? Methods This was a 2-phase retrospective matched-pair study of patients who underwent THA in 2007–2013. All procedures were performed by surgeons with at least 10 years’ experience as senior consultant. In the first phase, 58 patients aged 65 years or more who received tranexamic acid were matched 1:1 with patients who did not receive tranexamic acid for age, sex, American Society of Anesthesiologists (ASA) classification and body mass index. In the second phase, 58 patients aged 65 years or more who received tranexamic acid were matched 1:1 with patients less than 65 years of age who received tranexamic acid for sex, ASA classification and body mass index. The primary outcome measures were percent maximum decrease in hemoglobin level and estimated blood loss after surgery. Results In the first phase, patients who received tranexamic acid conserved postoperative hemoglobin by a mean of 10.26 g/L (standard deviation [SD] 9.89 g/L) compared to the control group (p < 0.001). The mean difference in the estimated perioperative blood loss between the 2 groups was 410 mL (SD 376 mL) (p < 0.001), which indicated less bleeding in the treatment group. In the second phase, there was no difference between the younger (mean age 55.1 [SD 7.28] yr) and older (mean age 75.6 [SD 6.35] yr) groups in mean lowest postoperative hemoglobin level or percent decrease in hemoglobin level. Conclusion Tranexamic acid reduced the postoperative decrease in hemoglobin level and blood loss in older patients. Moreover, the significant hemoglobin-sparing effect of tranexamic acid in older patients was similar to that observed in younger patients. PMID:29806815

INVESTIGATION OF THE RADICAL-MEDIATED PRODUCTION OF BENZENE OXIDE PROTEIN ADDUCTS IN VITRO AND IN VIVO

EPA Science Inventory

High background levels of benzene oxide (BO) adducts with hemoglobin and albumin (BO-Hb and BO-Alb) have been measured in unexposed humans and animals. To test the influence of radical-mediated pathways on production of these BO-protein adducts, we employed Fenton chemistry to...

Monoclonal antibodies to human hemoglobin S and cell lines for the production thereof

DOEpatents

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

1984-11-29

The present invention provides monoclonal antibodies specific to and distinguishing between hemoglobin S and hemoglobin A and methods for their production and use. These antibodies are capable of distinguishing between two hemoglobin types which differ from each other by only a single amino acid residue. The antibodies produced according to the present method are useful as immunofluorescent markers to enumerate circulating red blood cells which have the property of altered expression of the hemoglobin gene due to somatic mutation in stem cells. Such a measurement is contemplated as an assay for in vivo cellular somatic mutations in humans. Since the monoclonal antibodies produced in accordance with the instant invention exhibit a high degree of specificity to and greater affinity for hemoglobin S, they are suitable for labeling human red blood cells for flow cytometric detection of hemoglobin genotype. 4 figs.

Modeling hemoglobin at optical frequency using the unconditionally stable fundamental ADI-FDTD method.

PubMed

Heh, Ding Yu; Tan, Eng Leong

2011-04-12

This paper presents the modeling of hemoglobin at optical frequency (250 nm - 1000 nm) using the unconditionally stable fundamental alternating-direction-implicit finite-difference time-domain (FADI-FDTD) method. An accurate model based on complex conjugate pole-residue pairs is proposed to model the complex permittivity of hemoglobin at optical frequency. Two hemoglobin concentrations at 15 g/dL and 33 g/dL are considered. The model is then incorporated into the FADI-FDTD method for solving electromagnetic problems involving interaction of light with hemoglobin. The computation of transmission and reflection coefficients of a half space hemoglobin medium using the FADI-FDTD validates the accuracy of our model and method. The specific absorption rate (SAR) distribution of human capillary at optical frequency is also shown. While maintaining accuracy, the unconditionally stable FADI-FDTD method exhibits high efficiency in modeling hemoglobin.

Modeling hemoglobin at optical frequency using the unconditionally stable fundamental ADI-FDTD method

PubMed Central

Heh, Ding Yu; Tan, Eng Leong

2011-01-01

This paper presents the modeling of hemoglobin at optical frequency (250 nm – 1000 nm) using the unconditionally stable fundamental alternating-direction-implicit finite-difference time-domain (FADI-FDTD) method. An accurate model based on complex conjugate pole-residue pairs is proposed to model the complex permittivity of hemoglobin at optical frequency. Two hemoglobin concentrations at 15 g/dL and 33 g/dL are considered. The model is then incorporated into the FADI-FDTD method for solving electromagnetic problems involving interaction of light with hemoglobin. The computation of transmission and reflection coefficients of a half space hemoglobin medium using the FADI-FDTD validates the accuracy of our model and method. The specific absorption rate (SAR) distribution of human capillary at optical frequency is also shown. While maintaining accuracy, the unconditionally stable FADI-FDTD method exhibits high efficiency in modeling hemoglobin. PMID:21559129

[The Relevance of Hemolysis in Anesthesia and Intensive Care Medicine].

PubMed

Graw, Jan A; Baron, David M; Francis, Roland C E

2018-04-01

Hemolysis leads to an increase of circulating intravascular cell-free hemoglobin. Increased plasma concentrations of cell-free hemoglobin are relevant in critically ill patients because cell-free hemoglobin causes vasoconstriction by depletion of endothelial nitric oxide, oxidative stress, and inflammation. Furthermore, cell-free hemoglobin contributes to tissue injuries such as renal failure and intestinal mucosa damage after cardiac surgery. High concentrations of cell-free hemoglobin are associated with an increased mortality in patients with sepsis. Currently, it is unclear if hemolysis associated with transfusion of packed red blood cells that have been stored for prolonged periods of time is relevant for the clinical outcome. However, humans possess plasma proteins haptoglobin and hemopexin which bind to plasma hemoglobin and cell-free heme, respectively. The haptoglobin-hemoglobin and hemopexin-heme complexes are then eliminated from the plasma by hepatic or splenic uptake. Georg Thieme Verlag KG Stuttgart · New York.

High-Efficiency Synthesis of Human α-Endorphin and Magainin in the Erythrocytes of Transgenic Mice: A Production System for Therapeutic Peptides

NASA Astrophysics Data System (ADS)

Sharma, Ajay; Khoury-Christianson, Anastasia M.; White, Steven P.; Dhanjal, Nirpal K.; Huang, Wen; Paulhiac, Clara; Friedman, Eric J.; Manjula, Belur N.; Kumar, Ramesh

1994-09-01

Chemical synthesis of peptides, though feasible, is hindered by considerations of cost, purity, and efficiency of synthesizing longer chains. Here we describe a transgenic system for producing peptides of therapeutic interest as fusion proteins at low cost and high purity. Transgenic hemoglobin expression technology using the locus control region was employed to produce fusion hemoglobins in the erythrocytes of mice. The fusion hemoglobin contains the desired peptide as an extension at the C end of human α-globin. A protein cleavage site is inserted between the C end of the α-globin chain and the N-terminal residue of the desired peptide. The peptide is recovered after cleavage of the fusion protein with enzymes that recognize this cleavage signal as their substrate. Due to the selective compartmentalization of hemoglobin in the erythrocytes, purification of the fusion hemoglobin is easy and efficient. Because of its compact and highly ordered structure, the internal sites of hemoglobin are resistant to protease digestion and the desired peptide is efficiently released and recovered. The applicability of this approach was established by producing a 16-mer α-endorphin peptide and a 26-mer magainin peptide in transgenic mice. Transgenic animals and their progeny expressing these fusion proteins remain healthy, even when the fusion protein is expressed at >25% of the total hemoglobin in the erythrocytes. Additional applications and potential improvements of this methodology are discussed.

Subunit assembly of hemoglobin: an important determinant of hematologic phenotype.

PubMed

Bunn, H F

1987-01-01

Hemoglobin's physiologic properties depend on the orderly assembly of its subunits in erythropoietic cells. The biosynthesis of alpha- and beta-globin polypeptide chains is normally balanced. Heme rapidly binds to the globin subunit, either during translation or shortly thereafter. The formation of the alpha beta-dimer is facilitated by electrostatic attraction of a positively charged alpha-subunit to a negatively charged beta-subunit. The alpha beta-dimer dissociates extremely slowly. The difference between the rate of dissociation of alpha beta- and alpha gamma-dimers with increasing pH explains the well-known alkaline resistance of Hb F. Two dimers combine to form the functioning alpha 2 beta 2-tetramer. This model of hemoglobin assembly explains the different levels of positively charged and negatively charged mutant hemoglobins that are encountered in heterozygotes and the effect of alpha-thalassemia and heme deficiency states in modifying the level of the variant hemoglobin as well as Hb A2. Electrostatic interactions also affect the binding of hemoglobin to the cytoplasmic surface of the red cell membrane and may underlie the formation of target cells. Enhanced binding of positively charged variants such as S and C trigger a normally dormant pathway for potassium and water loss. Thus, the positive charge on beta c is responsible for the two major contributors to the pathogenesis of Hb SC disease: increased proportion of Hb S and increased intracellular hemoglobin concentration. It is likely that electrostatic interactions play an important role in the assembly of a number of other multisubunit macromolecules, including membrane receptors, cytoskeletal proteins, and DNA binding proteins.

Prevalence of Iron Deficiency Anaemia Among School Children in Kenitra, Northwest of Morocco.

PubMed

Achouri, I; Aboussaleh, Y; Sbaibi, R; Ahami, A; El Hioui, M

2015-04-01

Iron deficiency anaemia is an important health problem in Morocco. This study was conducted to estimate the prevalence of anaemia among school children in Kenitra. The sample represents school children of all educational levels and age ranged between 6-15 years. The level of hemoglobin, haematocrit, mean corpuscular volume, mean corpuscular hemoglobin and mean corpuscular hemoglobin concentration was measured in a group of 271 school children. The seric iron was assessed and anaemia was defined when hemoglobin < 11.5 g dL(-1). A questionnaire was developed to obtain information about the daily food consumption and socio-economic conditions. The prevalence of anaemia was 16.2%. The mean hemoglobin concentration was 12.53 g dL(-1) in boys and 12.52 g dL(-1) in girls. The results suggest that iron deficiency is an important determinant of anaemia in this population. There was a significant relationship between education of the mother and anaemia in children (p = 0.004) but not with the family income. It is concluded that improving the economic status of the family, women education and health education about balanced animal and plant food consumption are recommended strategies to reduce the burden of anaemia.

Differences in the clinical and genotypic presentation of sickle cell disease around the world

PubMed Central

Saraf, Santosh L.; Molokie, Robert E.; Nouraie, Mehdi; Sable, Craig A.; Luchtman-Jones, Lori; Ensing, Gregory J.; Campbell, Andrew D.; Rana, Sohail R.; Niu, Xiao M.; Machado, Roberto F.; Gladwin, Mark T.; Gordeuk, Victor R.

2014-01-01

Summary Sickle cell disease (SCD), caused by a mutation in the β-globin gene HBB, is widely distributed in malaria endemic regions. Cardiopulmonary complications are major causes of morbidity and mortality. Hemoglobin SS (Hb SS) represents a large proportion of SCD in the Americas, United Kingdom, and certain regions of Africa while higher proportions of hemoglobin SC are observed in Burkina Faso and hemoglobin Sβ-thalassemia in Greece and India. Coinheritance of α-thalassemia and persistence of hemoglobin F production are observed in highest frequency in certain regions of India and the Middle East. As confirmed in the PUSH and Walk-PHaSST studies, Hb SS, absence of co-inheriting alpha-thalassemia, and low hemoglobin F levels tend to be associated with more hemolysis, lower hemoglobin oxygen saturations, greater proportions of elevated tricuspid regurgitant jet velocity and brain natriuretic peptide, and increased left ventricular mass index. Identification of additional genetic modifiers will improve prediction of cardiopulmonary complications in SCD. PMID:24361300

Maternal hemoglobin concentration and adverse pregnancy outcomes at low and moderate altitudes in Peru.

PubMed

Gonzales, Gustavo F; Tapia, Vilma; Gasco, Manuel; Carrillo, Carlos E

2012-07-01

To identify associations of maternal hemoglobin (Hb) with perinatal outcomes at low and moderate altitudes in Peru. Study of records with sequential information using perinatal database system. The study included 295 651 pregnant women with their products. Using multiple logistic regression analysis, we estimated the probability of stillbirths, preterm and small for gestational age (SGA) births associated with maternal Hb levels at low (0-1999 m) and moderate altitudes (2000-2999 m). Maternal Hb decreased as pregnancy progressed from first to third trimester at both altitudes. Hb was higher at moderate than at low altitude (p < 0.001). Risks for stillbirths increased with low maternal Hb (odds ratio [OR]: 1.39 for Hb 9-9.9; OR: 1.84 for Hb 8-8.9; OR: 3.25 for Hb 7-7.9; and OR: 7.8 for Hb <7 g/dl); with Hb higher than 14.5 g/dl (OR: 1.31) and with altitudes ≥ 2000 m (OR: 1.2). High preterm rates were also observed with low Hbs (OR: 1.16 for Hb 9-9.9; OR: 1.64 for Hb 8-8.9; OR: 2.25 for Hb 7-7.9; and OR:2.87 for Hb<7 g/dl) and with Hb higher than 14.5 g/dl (OR: 1.14). High SGA rates were observed in neonates with maternal Hb of 7-7.9 (OR: 1.35) and <7 g/dl (OR:1.57), and higher than 14.5 g/dl (OR: 1.33), and with moderate altitudes (OR: 1.12). The cut-off points for lower risks of stillbirth and preterm births was 10 g/dl, and for SGA 9 g/dl of hemoglobin. Low and high maternal Hb levels and moderate altitude were independent risk factors for adverse perinatal outcomes.

Decreased lung function with mediation of blood parameters linked to e-waste lead and cadmium exposure in preschool children.

PubMed

Zeng, Xiang; Xu, Xijin; Boezen, H Marike; Vonk, Judith M; Wu, Weidong; Huo, Xia

2017-11-01

Blood lead (Pb) and cadmium (Cd) levels have been associated with lower lung function in adults and smokers, but whether this also holds for children from electronic waste (e-waste) recycling areas is still unknown. To investigate the contribution of blood heavy metals and lung function levels, and the relationship among living area, the blood parameter levels, and the lung function levels, a total of 206 preschool children from Guiyu (exposed area), and Haojiang and Xiashan (reference areas) were recruited and required to undergo blood tests and lung function tests during the study period. Preschool children living in e-waste exposed areas were found to have a 1.37 μg/dL increase in blood Pb, 1.18 μg/L increase in blood Cd, and a 41.00 × 10 9 /L increase in platelet counts, while having a 2.82 g/L decrease in hemoglobin, 92 mL decrease in FVC and 86 mL decrease in FEV 1 . Each unit of hemoglobin (1 g/L) decline was associated with 5 mL decrease in FVC and 4 mL decrease in FEV 1 . We conclude that children living in e-waste exposed area have higher levels of blood Pb, Cd and platelets, and lower levels of hemoglobin and lung function. Hemoglobin can be a good predictor for lung function levels. Copyright © 2017 Elsevier Ltd. All rights reserved.

Health status of copper refinery workers with specific reference to selenium exposure

DOE Office of Scientific and Technical Information (OSTI.GOV)

Holness, D.L.; Taraschuk, I.G.; Nethercott, J.R.

1989-09-01

Copper refinery workers exposed to selenium were studied before, during, and after a shutdown period. Urine selenium levels were 83 {plus minus} 30 mumol/mol creatinine and 69 {plus minus} 27 mumol/mol creatinine when measured on two occasions during exposure compared with 56 {plus minus} 17 mumol/mol creatinine when the workers had been free of exposure for 10 wk during a shutdown. The refinery workers reported more nose and eye irritation, indigestion, stomach pain, and fatigue than controls. Garlic-like breath odor was reported to be personally and socially offensive by many of the workers. Reporting of symptoms, pulmonary function indices, andmore » laboratory test results did not change with exposure except for hemoglobin level, which rose during the shutdown. Hemoglobin levels were found to be inversely correlated with the urine selenium level, and there was a positive correlation noted for the interactive effect of urine selenium and urine arsenic levels on hemoglobin.49 references.« less

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

PubMed

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

Hb Molfetta [beta126(H4)Val-->Leu, GTG-->CTG]: a new, silent, neutral beta chain variant found in an Italian woman.

PubMed

Qualtieri, Antonio; Le, Pera Maria; Pedace, Vera; Magariello, Angela; Brancati, Carlo

2002-02-01

We have identified a new neutral hemoglobin variant in a pregnant Italian woman, that resulted from a GTG-->CTG replacement at codon 126 of the beta chain, corresponding to a Val-->Leu amino acid change at position beta126(H4). Thermal and isopropanol stability tests were normal and there were no abnormal clinical features. Routine electrophoretic and ion exchange chromatographic methods for hemoglobin separation failed to show this variant, but reversed phase high performance liquid chromatography revealed an abnormal peak eluting near the normal beta chain. No abnormal tryptic peptide was revealed on the high performance liquid chromatographic elution pattern of the total globin digest. The mutation was determined at the DNA level by amplification of the three beta exons by polymerase chain reaction and direct sequencing of one exon that showed an abnormal migration on single strand conformational polymorphism analysis.

Cinnamon Use in Type 2 Diabetes: An Updated Systematic Review and Meta-Analysis

PubMed Central

Allen, Robert W.; Schwartzman, Emmanuelle; Baker, William L.; Coleman, Craig I.; Phung, Olivia J.

2013-01-01

PURPOSE Cinnamon has been studied in randomized controlled trials (RCTs) for its glycemic-lowering effects, but studies have been small and show conflicting results. A prior meta-analysis did not show significant results, but several RCTs have been published since then. We conducted an updated systematic review and meta-analysis of RCTs evaluating cinnamon’s effect on glycemia and lipid levels. METHODS MEDLINE, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) were searched through February 2012. Included RCTs evaluated cinnamon compared with control in patients with type 2 diabetes and reported at least one of the following: glycated hemoglobin (A1c), fasting plasma glucose, total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), or triglycerides. Weighted mean differences (with 95% confidence intervals) for endpoints were calculated using random-effects models. RESULTS In a meta-analysis of 10 RCTs (n = 543 patients), cinnamon doses of 120 mg/d to 6 g/d for 4 to 18 weeks reduced levels of fasting plasma glucose (−24.59 mg/dL; 95% CI, −40.52 to −8.67 mg/dL), total cholesterol (−15.60 mg/dL; 95% CI, −29.76 to −1.44 mg/dL), LDL-C (−9.42 mg/dL; 95% CI, −17.21 to −1.63 mg/dL), and triglycerides (−29.59 mg/dL; 95% CI, −48.27 to −10.91 mg/dL). Cinnamon also increased levels of HDL-C (1.66 mg/dL; 95% CI, 1.09 to 2.24 mg/dL). No significant effect on hemoglobin A1c levels (−0.16%; 95%, CI −0.39% to 0.02%) was seen. High degrees of heterogeneity were present for all analyses except HDL-C (I2 ranging from 66.5% to 94.72%). CONCLUSIONS The consumption of cinnamon is associated with a statistically significant decrease in levels of fasting plasma glucose, total cholesterol, LDL-C, and triglyceride levels, and an increase in HDL-C levels; however, no significant effect on hemoglobin A1c was found. The high degree of heterogeneity may limit the ability to apply these results to patient care, because the preferred dose and duration of therapy are unclear. PMID:24019277

Gene Therapy in a Patient with Sickle Cell Disease.

PubMed

Ribeil, Jean-Antoine; Hacein-Bey-Abina, Salima; Payen, Emmanuel; Magnani, Alessandra; Semeraro, Michaela; Magrin, Elisa; Caccavelli, Laure; Neven, Benedicte; Bourget, Philippe; El Nemer, Wassim; Bartolucci, Pablo; Weber, Leslie; Puy, Hervé; Meritet, Jean-François; Grevent, David; Beuzard, Yves; Chrétien, Stany; Lefebvre, Thibaud; Ross, Robert W; Negre, Olivier; Veres, Gabor; Sandler, Laura; Soni, Sandeep; de Montalembert, Mariane; Blanche, Stéphane; Leboulch, Philippe; Cavazzana, Marina

2017-03-02

Sickle cell disease results from a homozygous missense mutation in the β-globin gene that causes polymerization of hemoglobin S. Gene therapy for patients with this disorder is complicated by the complex cellular abnormalities and challenges in achieving effective, persistent inhibition of polymerization of hemoglobin S. We describe our first patient treated with lentiviral vector-mediated addition of an antisickling β-globin gene into autologous hematopoietic stem cells. Adverse events were consistent with busulfan conditioning. Fifteen months after treatment, the level of therapeutic antisickling β-globin remained high (approximately 50% of β-like-globin chains) without recurrence of sickle crises and with correction of the biologic hallmarks of the disease. (Funded by Bluebird Bio and others; HGB-205 ClinicalTrials.gov number, NCT02151526 .).

Locally Advanced Stage IV Squamous Cell Carcinoma of the Head and Neck: Impact of Pre-Radiotherapy Hemoglobin Level and Interruptions During Radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rades, Dirk; Department of Radiation Oncology, University Medical Center Hamburg-Eppendorf, Hamburg; Stoehr, Monika

2008-03-15

Purpose: Stage IV head and neck cancer patients carry a poor prognosis. Clear understanding of prognostic factors can help to optimize care for the individual patient. This study investigated 11 potential prognostic factors including pre-radiotherapy hemoglobin level and interruptions during radiotherapy for overall survival (OS), metastases-free survival (MFS), and locoregional control (LC) after radiochemotherapy. Methods and Materials: Eleven factors were investigated in 153 patients receiving radiochemotherapy for Stage IV squamous cell head and neck cancer: age, gender, Karnofsky performance score (KPS), tumor site, grading, T stage, N stage, pre-radiotherapy hemoglobin level, surgery, chemotherapy type, and interruptions during radiotherapy >1 week.more » Results: On multivariate analysis, improved OS was associated with KPS 90-100 (relative risk [RR], 2.36; 95% confidence interval [CI], 1.20-4.93; p = .012), hemoglobin {>=}12 g/dL (RR, 1.88; 95% CI, 1.01-3.53; p = .048), and no radiotherapy interruptions (RR, 2.59; 95% CI, 1.15-5.78; p = .021). Improved LC was significantly associated with lower T stage (RR, 2.17; 95% CI, 1.16-4.63; p = .013), hemoglobin {>=}12 g/dL (RR, 4.12; 95% CI, 1.92-9.09; p < .001), surgery (RR, 2.67; 95% CI, 1.28-5.88; p = .008), and no radiotherapy interruptions (RR, 3.32; 95% CI, 1.26-8.79; p = .015). Improved MFS was associated with KPS 90-100 (RR, 3.41; 95% CI, 1.46-8.85; p = .012). Conclusions: Significant predictors for outcome in Stage IV head and neck cancer were performance status, stage, surgery, pre-radiotherapy hemoglobin level, and interruptions during radiotherapy >1 week. It appears important to avoid anemia and radiotherapy interruptions to achieve the best treatment results.« less

Oral Iron Supplementation After Blood Donation

PubMed Central

Kiss, Joseph E.; Brambilla, Donald; Glynn, Simone A.; Mast, Alan E.; Spencer, Bryan R.; Stone, Mars; Kleinman, Steven H.; Cable, Ritchard G.

2016-01-01

IMPORTANCE Although blood donation is allowed every 8 weeks in the United States, recovery of hemoglobin to the currently accepted standard (12.5 g/dL) is frequently delayed, and some donors become anemic. OBJECTIVE To determine the effect of oral iron supplementation on hemoglobin recovery time (days to recovery of 80% of hemoglobin removed) and recovery of iron stores in iron-depleted (“low ferritin,” ≤26 ng/mL) and iron-replete (“higher ferritin,” >26 ng/mL) blood donors. DESIGN, SETTING, AND PARTICIPANTS Randomized, nonblinded clinical trial of blood donors stratified by ferritin level, sex, and age conducted in 4 regional blood centers in the United States in 2012. Included were 215 eligible participants aged 18 to 79 years who had not donated whole blood or red blood cells within 4 months. INTERVENTIONS One tablet of ferrous gluconate (37.5 mg of elemental iron) daily or no iron for 24 weeks (168 days) after donating a unit of whole blood (500 mL). MAIN OUTCOMES AND MEASURES Time to recovery of 80% of the postdonation decrease in hemoglobin and recovery of ferritin level to baseline as a measure of iron stores. RESULTS The mean baseline hemoglobin levels were comparable in the iron and no-iron groups and declined from a mean (SD) of 13.4 (1.1) g/dL to 12.0 (1.2) g/dL after donation in the low-ferritin group and from 14.2 (1.1) g/dL to 12.9 (1.2) g/dL in the higher-ferritin group. Compared with participants who did not receive iron supplementation, those who received iron supplementation had shortened time to 80% hemoglobin recovery in both the low-ferritin and higher-ferritin groups. Recovery of iron stores in all participants who received supplements took a median of 76 days (IQR, 20–126); for participants not taking iron, median recovery time was longer than 168 days (IQR, 147->168 days; P < .001). Without iron supplements, 67% of participants did not recover iron stores by 168 days. Low-Ferritin Group (≤26 ng/mL) Higher-Ferritin Group (>26 ng/mL) IronNo IronIronNo Iron Time to 80% hemoglobin recovery, mean (IQR), d32 (30–34)158 (126–>168)31 (29–33)78 (66–95) Time to recovery of baseline ferritin levels, median (IQR), d21 (12–84)>168 (128–>168)107 (75–141)>168 (>168–>168) CONCLUSIONS AND RELEVANCE Among blood donors with normal hemoglobin levels, low-dose iron supplementation, compared with no supplementation, reduced time to 80% recovery of the postdonation decrease in hemoglobin concentration in donors with low ferritin (≤26 ng/mL) or higher ferritin (>26 ng/mL). TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01555060 PMID:25668261

Implementation of the Diabetes Practice Guideline in the Army Medical Department: Final Evaluation

DTIC Science & Technology

2005-01-01

Diabetes Quality Improvement Project DRG Diagnosis-Related Group ER Emergency room FMP Family Member Prefix HBA1c Hemoglobin A1c HCSR Health-Care Service...glycemic control by assessing and managing glycosylated hemoglobin, reported as hemoglobin A1c ( HbA1c ) lev- els. Assess HbA1c levels relative to target...frequency involved in adjusting insulin dosages Increase in the percentage of noninsulin patients who fill prescribed medications to control HbA1c

Effects of school-based deworming on hemoglobin level, growth development and school performance of primary school children in North Sumatera

NASA Astrophysics Data System (ADS)

Pasaribu, A. P.; Angellee, J.; Pasaribu, S.

2018-03-01

Worm infestation is mainly caused by soil-transmitted helminths (STH) infecting one-third of the world’s population, where the most affected are primary school children. This chronic, long-lasting infection can affect the growth aspects in children. A school-based deworming is one of the treatments recommended by WHO to counterattack worm infection in primary school children. To evaluate the effect of school-based deworming on the hemoglobin level, growth and school performance of primary school children, an open randomized clinical trial was conducted on 165 targeted populations in SukaKaro village, North Sumatra; 156 of which were then chosen based on inclusion and exclusion criteria. The samples’ feces- sampling, hemoglobin level, and growth chart data were recorded on the first day of study before any treatment was given. They were then divided into two groups; the first group of 80 samples did not receive any treatment, while the second group of 76 samples received 400mg of albendazole as part of a school-based deworming program. The samples were being followed up after sixth months of study. In conclusion, albendazole is able to improve the hemoglobin level, growth development, and school performance of the samples, although there were no significant differences between the two groups.

Increased 2,3-Diphosphoglycerate During Normocapnic Hypobaric Hypoxia,

DTIC Science & Technology

Maintenance of normal plasma pH at high altitude (HA) by acetazolamide has been shown to prevent the HA-induced change in 2,3- diphosphoglycerate (DPG...had significant elevations in DPG above sea- level values after two days. Mean corpuscular hemoglobin concentrations (MCHC) remained within normal...limits during the first two days, then decreased significantly below sea- level values in Group I (days 3-5) and Group II (days 4-5). Thus prevention of

The hemoglobin system of the serpent eel Ophisurus serpens: structural and functional characterization.

PubMed

Manconi, Barbara; Pellegrini, Mariagiuseppina; Messana, Irene; Sanna, Maria Teresa; Castagnola, Massimo; Iavarone, Federica; Coluccia, Elisabetta; Giardina, Bruno; Olianas, Alessandra

2013-10-01

The hemoglobin system of the serpent eel Ophisurus serpens was structurally and functionally characterized with the aim of comparing it to the hemoglobin system of other fish species, as oxygen loading under the severe habitat conditions experienced by O. serpens could have necessitated specific adaptation mechanisms during evolution. The hemoglobin system of O. serpens includes one cathodic and four anodic components. The molecular mass of the α and β chains of the cathodic component as well as the 2 α and 4 β of the anodic components were determined. Analysis of the intact α and β chains from cathodic hemoglobin and their proteolytic digestion products by high-resolution MS and MS/MS experiments resulted in 92 and 95 % sequence coverage of the α and β globins, respectively. The oxygen binding properties of both hemoglobin components were analyzed with respect to their interactions with their physiological effectors. Stripped cathodic hemoglobin displayed the highest oxygen affinity among Anguilliformes with no significant effect of pH on O2-affinity. In the presence of both chloride and organic phosphates, O2-affinity was strongly reduced, and cooperativity was enhanced; moreover, cathodic hemoglobin contains two indistinguishable GTP-binding sites. Stripped anodic hemoglobins exhibited both low O2-affinity and low cooperativity and a larger Bohr effect than cathodic hemoglobin. The cathodic hemoglobin of O. serpens and the corresponding component of Conger conger share the greatest structural and functional similarity among hemoglobin systems of Anguilliformes studied to date, consistent with their phylogenetic relationship.

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

PubMed Central

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

2017-01-01

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

Clinical study of repaglinide efficacy and safety in type 2 diabetes mellitus patients with blood glucose levels inadequately controlled by sitagliptin.

PubMed

Kawamori, Ryuzo; Kaku, Kohei; Hanafusa, Toshiaki; Ioriya, Katsuhisa; Kageyama, Shigeru; Hotta, Nigishi

2016-03-01

The aim of the present study was to evaluate the long-term efficacy and safety of adding repaglinide in patients with type 2 diabetes mellitus whose blood glucose levels were not sufficiently controlled by treatment with a dipeptidyl peptidase-4 inhibitor, sitagliptin, in addition to diet and exercise therapies. This was a multicenter, uncontrolled, dose-titration study with a treatment period of 52 weeks. The primary end-point was the change in glycated hemoglobin levels from baseline. The glycated hemoglobin level was 7.43 ± 0.57% (mean ± standard deviation) at baseline, and decreased to 6.93 ± 0.91% at the end of the study. The mean changes in glycated hemoglobin levels at 4 weeks and at the end of the study were -0.44 ± 0.28% and -0.50 ± 0.82%, respectively. The glycated hemoglobin-lowering effect was maintained for 52 weeks. The rate of adverse events was 86.0% (86/100), and there were 352 adverse events. The rate of adverse drug reactions was 21.0% (21/100). Hypoglycemia was reported in 5.0% (5/100) of patients, but there was no incidence of 'major hypoglycemia'. Combination therapy with repaglinide and sitagliptin was considered effective for a long term without clinical safety problems in patients with type 2 diabetes mellitus.

Effect of NaFeEDTA-Fortified Soy Sauce on Anemia Prevalence in China: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

PubMed

Huo, Jun Sheng; Yin, Ji Yong; Sun, Jing; Huang, Jian; Lu, Zhen Xin; Regina, Moench-Pfanner; Chen, Jun Shi; Chen, Chun Ming

2015-11-01

To assess the effect of sodium iron ethylenediaminetetraacetate (NaFeEDTA)-fortified soy sauce on anemia prevalence in the Chinese population. A systematic review was performed to identify potential studies by searching the electronic databases of PubMed, Cochrane Library, WHO Library, HighWire, CNKI, and other sources. The selection criteria included randomized controlled trials that compared the efficacy of NaFeEDTA-fortified soy sauce with that of non-fortified soy sauce. Anemia rates and hemoglobin levels were the outcomes of interest. Inclusion decisions, quality assessment, and data extraction were performed by two reviewers independently. A total of 16 studies met the inclusion criteria for anemia rate analysis, of which 12 studies met the inclusion criteria for hemoglobin analysis. All included studies assessed the effect of NaFeEDTA-fortified soy sauce on anemia rates and hemoglobin concentrations. After the intervention, the hemoglobin concentration increased and anemia rates decreased significantly as compared with the non-fortified soy sauce groups. For anemia rates, data from 16 studies could be pooled, and the pooled estimate odds ratio was 0.25 (95% CI 0.19-0.35). For hemoglobin concentrations, data from 12 studies could be pooled, and the pooled weighted mean difference was 8.81 g/L (95% CI 5.96-11.67). NaFeEDTA-fortified soy sauce has a positive effect on anemia control and prevention in the at-risk population. Copyright © 2015 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.

Erythrocyte enzymes in groups of Rattus norvegicus with genetic differences in 2,3-diphosphoglycerate levels.

PubMed

Noble, N A; Tanaka, K R

1979-01-01

1. A major locus with two alleles is responsible for large differences in erythrocyte 2,3-diphosphoglycerate (DPG) levels in Rattus norvegicus. Blood from homozygous High-DPG, homozygous Low-DPG and heterozygous animals was used to measure blood indices and red cell enzyme activities. 2. Significant differences between groups were found in DPG levels, white blood cell counts and hemoglobin levels. 3. The results suggest that none of the red cell enzymes assayed is structurally or quantitatively different in the three groups.

V. THE IRON CONTENT OF BLOOD FREE TISSUES AND VISCERA

PubMed Central

Bogniard, Robert P.; Whipple, George H.

1932-01-01

When hemoglobin is set free in the circulation the kidney plays an important part in the conservation of iron. When the renal threshold is not exceeded by the hemoglobin in the blood there is little or no excess iron deposited in the kidney but when superthreshold doses of blood hemoglobin are given the epithelium of the convoluted tubules accumulates much iron and the iron analyses may show 5 times normal values. The normal dog (140 to 150 per cent hemoglobin) has a large reserve store of iron in the liver, spleen and marrow. Diets may modify this storage of iron in these tissues. To bring conclusive proof relating to the individual diet factors, the reserve store of iron should be depleted by an anemia period of 2 to 3 months. Complete removal of red cells from tissue capillaries is essential for accurate iron assays of fresh tissue. The method described accomplishes this without causing gross tissue edema. The lowest iron content is observed in the pancreas, stomach, jejunum, colon and urinary bladder. These figures average from 1 to 2 mg. iron per 100 gm. fresh tissue. This shows that smooth muscle and mucous membranes contain little iron. Striated muscle (heart, psoas) shows a relatively low iron content but uniform values close to 4 mg. per 100 gm. tissue. Lungs show a considerable fluctuation with low iron values in anemia (3.7 mg.) and higher values in health (6 to 7 mg.). The spleen shows maximal fluctuations and the highest reserve storage of iron per 100 gm. fresh tissue. The spleen iron analyses show low values in anemia (7 to 15 mg.) and wide differences in controls (25 to 50 mg.). With hemoglobin injections the iron storage is conspicuous and iron analyses may run as high as l50 to 175 mg. iron per 100 gm. fresh tissue. Bone marrow of the rib runs in parallel with the spleen as regards iron storage following hemoglobin injections and depletion following anemia periods. The liver because of its weight always contains the main bulk of the iron stored in the blood free tissues of the body. Its store is depleted by anemia even to levels of 4 to 5 mg. iron per 100 gm. fresh tissue. In the normal dog the iron store in the liver averages 25 mg. per 100 gm. tissue. Frequent hemoglobin injections may increase this level to 31 mg. iron per 100 gm. The liver is considered the most active clearing house for iron storage and utilization. PMID:19870020

Thalassemia and Hemoglobin E in Southern Thai Blood Donors

PubMed Central

Kruachan, Kwanta; Sengking, Warachaya; Horpet, Dararat; Sungyuan, Ubol

2014-01-01

Thalassemia and hemoglobin E (Hb E) are common in Thailand. Individuals with thalassemia trait usually have a normal hemoglobin concentration or mild anemia. Therefore, thalassemic individuals who have minimum acceptable Hb level may be accepted as blood donors. This study was aimed at determining the frequency of α-thalassemia 1 trait, β-thalassemia trait, and Hb E-related syndromes in Southern Thai blood donors. One hundred and sixteen voluntary blood donors, Southern Thailand origin, were recruited for thalassemia and Hb E screening by red blood cell indices/dichlorophenolindophenol precipitation test. β-Thalassemia and Hb E were then identified by high performance liquid chromatography and 4 common α-thalassemia deletions were characterized by a single tube-multiplex gap-polymerase chain reaction. Overall frequency of hemoglobinopathies was 12.9%, classified as follows: homozygous α-thalassemia 2 (1.7%), heterozygous α-thalassemia 1 (1.7%), heterozygous β-thalassemia without α-thalassemia (0.9%), heterozygous Hb E without α-thalassemia (5.2%), double heterozygotes for Hb E/α-thalassemia 1 (1.7%), homozygous Hb E without α-thalassemia (0.9%), and homozygous Hb E with heterozygous α-thalassemia 2 (0.9%). The usefulness of thalassemia screening is not only for receiving highly effective red blood cells in the recipients but also for encouraging the control and prevention program of thalassemia in blood donors. PMID:25050123

Noninvasive assessment of the risk of tobacco abuse in oral mucosa using fluorescence spectroscopy: a clinical approach

NASA Astrophysics Data System (ADS)

Nazeer, Shaiju S.; Asish, Rajashekharan; Venugopal, Chandrashekharan; Anita, Balan; Gupta, Arun Kumar; Jayasree, Ramapurath S.

2014-05-01

Tobacco abuse and alcoholism cause cancer, emphysema, and heart disease, which contribute to high death rates, globally. Society pays a significant cost for these habits whose first demonstration in many cases is in the oral cavity. Oral cavity disorders are highly curable if a screening procedure is available to diagnose them in the earliest stages. The aim of the study is to identify the severity of tobacco abuse, in oral cavity, as reflected by the emission from endogenous fluorophores and the chromophore hemoglobin. A group who had no tobacco habits and another with a history of tobacco abuse were included in this study. To compare the results with a pathological condition, a group of leukoplakia patients were also included. Emission from porphyrin and the spectral filtering modulation effect of hemoglobin were collected from different sites. Multivariate analysis strengthened the spectral features with a sensitivity of 60% to 100% and a specificity of 76% to 100% for the discrimination. Total hemoglobin and porphyrin levels of habitués and leukoplakia groups were comparable, indicating the alarming situation about the risk of tobacco abuse. Results prove that fluorescence spectroscopy along with multivariate analysis is an effective noninvasive tool for the early diagnosis of pathological changes due to tobacco abuse.

Factors affecting response and tolerability to ferumoxytol in nondialysis chronic kidney disease patients.

PubMed

Fishbane, Steven; Bolton, W Kline; Winkelmayer, Wolfgang C; Strauss, William; Li, Zhu; Pereira, Brian J G

2012-09-01

Ferumoxytol is a unique intravenous (i.v.) iron therapy. This report examines factors affecting hemoglobin response to i.v. ferumoxytol, and the relationship between hematologic parameters, concomitant erythropoiesis-stimulating agents (ESA), and adverse events (AEs) in nondialysis CKD patients. A series of post-hoc efficacy and safety analyses were performed using pooled data from two identically designed Phase III studies in 608 nondialysis CKD patients randomized to receive two 510 mg i.v. injections of ferumoxytol within 5 ± 3 days versus oral iron. Ferumoxytol resulted in a significant increase in hemoglobin in the presence and absence of ESA, and across a range of baseline hemoglobin, transferrin saturation, ferritin, and reticulocyte hemoglobin content levels. Adverse event rates with ferumoxytol were similar across quartiles of change in hemoglobin; there were no trends suggesting an increased rate of cardiovascular AEs with higher maximum achieved hemoglobin or faster rate of hemoglobin rise. There was no meaningful difference in the rate of AEs, serious AEs, and cardiovascular AEs between patients receiving or not receiving ESA. These analyses add to the knowledge of predictors of response and safety outcomes associated with i.v. iron therapy in nondialysis CKD patients.

Frontal cortical oxygenation changes during gravity-induced loss of consciousness in humans: a near-infrared spatially resolved spectroscopic study.

PubMed

Kurihara, Koichi; Kikukawa, Azusa; Kobayashi, Asao; Nakadate, Toshio

2007-10-01

Gravity (G)-induced loss of consciousness (G-LOC), which is presumably caused by a reduction of cerebral blood flow resulting in a decreased oxygen supply to the brain, is a major threat to pilots of high-performance fighter aircraft. The application of cerebral near-infrared spectroscopy (NIRS) to monitor gravity-induced cerebral oxygenation debt has generated concern over potential sources of extracranial contamination. The recently developed NIR spatially resolved spectroscopy (SRS-NIRS) has been confirmed to provide frontal cortical tissue hemoglobin saturation [tissue oxygenation index (TOI)]. In this study, we monitored the TOI and the standard NIRS measured chromophore concentration changes of oxygenated hemoglobin and deoxygenated hemoglobin in 141 healthy male pilots during various levels of +G(z) (head-to-foot inertial forces) exposure to identify the differences between subjects who lose consciousness and those who do not during high +G(z) exposure. Subjects were exposed to seven centrifuge profiles, with +G(z) levels from 4 to 8 G(z) and an onset rate from 0.1 to 6.0 G(z)/s. The SRS-NIRS revealed an approximately 15% decrease in the TOI in G-LOC. The present study also demonstrated the TOI to be a useful variable to evaluate the effect of the anti-G protection system. However, there was no significant difference found between conditions with and without G-LOC in subjects with terminated G exposure. Further studies that elucidate the mechanism(s) behind the wide variety of individual differences may be needed for a method of G-LOC prediction to be effectively realized.

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

PubMed

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.

The preparation and characterization of monomethoxypoly(ethylene glycol)-b-poly-DL-lactide microcapsules containing bovine hemoglobin.

PubMed

Meng, Fan-Tao; Zhang, Wan-Zhong; Ma, Guang-Hui; Su, Zhi-Guo

2003-08-01

Methoxypoly(ethylene glycol)-b-poly-DL-lactide (PELA) microcapsules containing bovine hemoglobin (bHb) were prepared by a W/O/W double emulsion-solvent diffusion process. bHb solution was used as the internal aqueous phase, PELA/organic solvent as the oil phase, and polyvinyl alcohol (PVA) solution as the external aqueous phase. This W/O/W double emulsion was added into a large volume of water (solidification solution) to allow organic solvent to diffuse into water. The optimum preparative condition for PELA microcapsules loaded with bovine hemoglobin was investigated. It was found that homogenization rate, type of organic solvent, and volume of the solidification solution influenced the activity of bovine hemoglobin encapsulated. When the homogenization rate was lower than 9000 rpm and ethyl acetate was used as the organic solvent, there was no significant influence on the activity of hemoglobin. High homogenization rate as 12 000 rpm decreased the P50 and Hill coefficient. Increasing the volume of solidification solution had an effect of improving the activity of microencapsulated hemoglobin. The composition of the PELA had the most important influence on the success of encapsulation. Microcapsules fabricated by PELA with MPEG2k block (molecular weight of MPEG block: 2000) achieved a high entrapment efficiency of 90%, better than PL A homopolymer and PELA with MPEG5k blocks. Hemoglobin microcapsules with native loading oxygen activity (P50 = 26.0 mmHg, Hill coefficient = 2.4), mean size of about 10 microm, and high entrapment efficiency (ca. 93%) were obtained at the optimum condition.

Is combined topical and intravenous tranexamic acid superior to single use of tranexamic acid in total joint arthroplasty?

PubMed Central

Yang, Liqing; Du, Shuai; Sun, Yuefeng

2017-01-01

Abstract Background: To compare the efficacy and safety of the combined application of both intravenous and topical tranexamic acid (TXA) versus the single use of either application in patients with total knee and hip arthroplasty (TKA and THA). Methods: Potentially relevant studies were identified from electronic databases including Medline, PubMed, Embase, ScienceDirect, and the Cochrane Library. Randomized control trials (RCTs) of patients prepared for total joint arthroplasty that compared combined TXA with placebo were retrieved. The primary endpoint was hemoglobin decline or postoperative hemoglobin level, blood loss, drainage volume, transfusion requirements. The secondary outcomes were length of stay (LOS), and operation time as well as surgery-related adverse effects, such as wound infection, deep vein thrombosis (DVT), and pulmonary embolism (PE). After testing for publication bias and heterogeneity between studies, data were aggregated for random-effects models when necessary. Results: Five RCTs that included 604 patients met the inclusion criteria. The present meta-analysis indicated significant differences existed in the total blood loss (mean difference [MD] = −134.65, 95% CI: −191.66 to −77.64, P < .0001), postoperative hemoglobin level (MD = 0.74, 95% CI: 0.39–1.10, P < .0001), drainage volume (MD = −47.44, 95% CI: −64.55 to −30.33, P < .00001), and transfusion rate (risk difference [RD] = −0.06, 95% CI: −0.10 to −0.02, P = .006) between groups. Conclusion: Combined administration of TXA in TKA and THA was associated with significantly reduced total blood loss, postoperative hemoglobin decline, drainage volume, and transfusion requirements. Well-designed, high-quality RCTs with long-term follow-up are still required. PMID:28746213

Efficacy and safety of subcutaneous administration of lyophilized powder of alfa-erythropoietin to maintain hemoglobin concentrations among hemodialysis patients.

PubMed

Satirapoj, Bancha; Dispan, Rattanawan; Supasyndh, Ouppatham

2017-01-01

Anemia associated with chronic kidney disease (CKD) often requires treatment with recombinant human erythropoietin (EPO). This study investigated the therapeutic equivalence between lyophilized powder and standard liquid EPO alfa by subcutaneous (SC) administration in hemoglobin maintenance among patients on hemodialysis. This was a single-blinded, randomized, controlled, single-center, parallel-group study regarding the treatment of anemia among CKD patients on hemodialysis and being treated with stable doses of EPO alfa at least for 12 weeks. Anemic hemodialysis patients (n=63) received standard liquid or lyophilized powder EPO alfa for 24 weeks by SC administration. Achievement of the target hemoglobin concentration and safety and tolerability end points were documented. Baseline mean hemoglobin level was 11.1±0.7 g/dL using lyophilized powder EPO alfa and 11.2±0.9 g/dL using standard liquid EPO alfa. The baseline median dose of EPO alfa was 126.4 (interquartile range [IQR] 81.6-163.6) U/kg/week in the lyophilized powder EPO alfa group and 116.9 (IQR 76.5-144.1) U/kg/week in the standard liquid EPO alfa group. Treatment with SC lyophilized powder EPO alfa maintained mean hemoglobin and hematocrit concentrations after switching from standard liquid EPO alfa. No statistical significance between groups was reported for hemoglobin concentrations and weekly dose of EPO alfa during the study. No safety concerns were raised, including positive anti-EPO antibodies. In this study of anemia therapy among patients with end-stage renal disease on hemodialysis therapy, the SC injection of lyophilized powder EPO alfa was well tolerated and effectively maintained hemoglobin levels. Future studies of larger size and longer duration will be required to assess safety profiles.

Perioperative factors associated with pressure ulcer development after major surgery

PubMed Central

2018-01-01

Background Postoperative pressure ulcers are important indicators of perioperative care quality, and are serious and expensive complications during critical care. This study aimed to identify perioperative risk factors for postoperative pressure ulcers. Methods This retrospective case-control study evaluated 2,498 patients who underwent major surgery. Forty-three patients developed postoperative pressure ulcers and were matched to 86 control patients based on age, sex, surgery, and comorbidities. Results The pressure ulcer group had lower baseline hemoglobin and albumin levels, compared to the control group. The pressure ulcer group also had higher values for lactate levels, blood loss, and number of packed red blood cell (pRBC) units. Univariate analysis revealed that pressure ulcer development was associated with preoperative hemoglobin levels, albumin levels, lactate levels, intraoperative blood loss, number of pRBC units, Acute Physiologic and Chronic Health Evaluation II score, Braden scale score, postoperative ventilator care, and patient restraint. In the multiple logistic regression analysis, only preoperative low albumin levels (odds ratio [OR]: 0.21, 95% CI: 0.05–0.82; P < 0.05) and high lactate levels (OR: 1.70, 95% CI: 1.07–2.71; P < 0.05) were independently associated with pressure ulcer development. A receiver operating characteristic curve was used to assess the predictive power of the logistic regression model, and the area under the curve was 0.88 (95% CI: 0.79–0.97; P < 0.001). Conclusions The present study revealed that preoperative low albumin levels and high lactate levels were significantly associated with pressure ulcer development after surgery. PMID:29441175

Comparison of Pre- and Postoperative Hemoglobin and Hematocrit Levels in Hip Arthroscopy

PubMed Central

Seijas, Roberto; Espinosa, Wenceslao; Sallent, Andrea; Cuscó, Xavier; Cugat, Ramón; Ares, Oscar

2015-01-01

Purpose : to assess the loss in hematocrit and hemoglobin, if any, 24 hours after hip arthroscopy. Methods : thirty-five patients were included. Laboratory tests including complete blood count and white blood cells were performed one week prior to surgery and 24 hours after. Surgical time, volume of saline perfusion and pump perfusion was also recorded. Results : mean preoperative hematocrit was 42.01% (4.63 SD), whereas mean postoperative hematocrit at 24 h decreased to 36.78% (SD 5.11) (p <0.021.). Mean preoperative hemoglobin was 14.23 g/dL (1.73 SD), and mean postoperative hemoglobin at 24 h decreased to 12.40 g/dL (SD 1.92) (p =0.03.). Platelets and white blood cells, as well as the remaining biochemical parameters showed no significant difference between preoperative and postoperative samples. Lost blood volume worked out with the logarithmic method for estimated blood loss was which 0.78 liters (SD 0.45). Lost blood volume taking into account, the red blood cell mass was also 0.78 liters (SD 0.45). Conclusion : a significant decrease in hemoglobin and hematocrit after hip arthroscopy was observed. Although patients did not show clinical signs of anemia or bleeding, blood loss should be considered when planning a hip arthroscopy, especially in patients at risk of anemia. According to our results, we recommend a postoperative control analysis at 24 h. Level of Evidence : level II, Diagnostic Study. PMID:26401169

Hemolytic anemia repressed hepcidin level without hepatocyte iron overload: lesson from Günther disease model

PubMed Central

Millot, Sarah; Delaby, Constance; Moulouel, Boualem; Lefebvre, Thibaud; Pilard, Nathalie; Ducrot, Nicolas; Ged, Cécile; Lettéron, Philippe; de Franceschi, Lucia; Deybach, Jean Charles; Beaumont, Carole; Gouya, Laurent; De Verneuil, Hubert; Lyoumi, Saïd; Puy, Hervé; Karim, Zoubida

2017-01-01

Hemolysis occurring in hematologic diseases is often associated with an iron loading anemia. This iron overload is the result of a massive outflow of hemoglobin into the bloodstream, but the mechanism of hemoglobin handling has not been fully elucidated. Here, in a congenital erythropoietic porphyria mouse model, we evaluate the impact of hemolysis and regenerative anemia on hepcidin synthesis and iron metabolism. Hemolysis was confirmed by a complete drop in haptoglobin, hemopexin and increased plasma lactate dehydrogenase, an increased red blood cell distribution width and osmotic fragility, a reduced half-life of red blood cells, and increased expression of heme oxygenase 1. The erythropoiesis-induced Fam132b was increased, hepcidin mRNA repressed, and transepithelial iron transport in isolated duodenal loops increased. Iron was mostly accumulated in liver and spleen macrophages but transferrin saturation remained within the normal range. The expression levels of hemoglobin-haptoglobin receptor CD163 and hemopexin receptor CD91 were drastically reduced in both liver and spleen, resulting in heme- and hemoglobin-derived iron elimination in urine. In the kidney, the megalin/cubilin endocytic complex, heme oxygenase 1 and the iron exporter ferroportin were induced, which is reminiscent of significant renal handling of hemoglobin-derived iron. Our results highlight ironbound hemoglobin urinary clearance mechanism and strongly suggest that, in addition to the sequestration of iron in macrophages, kidney may play a major role in protecting hepatocytes from iron overload in chronic hemolysis. PMID:28143953

Hemolytic anemia repressed hepcidin level without hepatocyte iron overload: lesson from Günther disease model.

PubMed

Millot, Sarah; Delaby, Constance; Moulouel, Boualem; Lefebvre, Thibaud; Pilard, Nathalie; Ducrot, Nicolas; Ged, Cécile; Lettéron, Philippe; de Franceschi, Lucia; Deybach, Jean Charles; Beaumont, Carole; Gouya, Laurent; De Verneuil, Hubert; Lyoumi, Saïd; Puy, Hervé; Karim, Zoubida

2017-02-01

Hemolysis occurring in hematologic diseases is often associated with an iron loading anemia. This iron overload is the result of a massive outflow of hemoglobin into the bloodstream, but the mechanism of hemoglobin handling has not been fully elucidated. Here, in a congenital erythropoietic porphyria mouse model, we evaluate the impact of hemolysis and regenerative anemia on hepcidin synthesis and iron metabolism. Hemolysis was confirmed by a complete drop in haptoglobin, hemopexin and increased plasma lactate dehydrogenase, an increased red blood cell distribution width and osmotic fragility, a reduced half-life of red blood cells, and increased expression of heme oxygenase 1. The erythropoiesis-induced Fam132b was increased, hepcidin mRNA repressed, and transepithelial iron transport in isolated duodenal loops increased. Iron was mostly accumulated in liver and spleen macrophages but transferrin saturation remained within the normal range. The expression levels of hemoglobin-haptoglobin receptor CD163 and hemopexin receptor CD91 were drastically reduced in both liver and spleen, resulting in heme- and hemoglobin-derived iron elimination in urine. In the kidney, the megalin/cubilin endocytic complex, heme oxygenase 1 and the iron exporter ferroportin were induced, which is reminiscent of significant renal handling of hemoglobin-derived iron. Our results highlight ironbound hemoglobin urinary clearance mechanism and strongly suggest that, in addition to the sequestration of iron in macrophages, kidney may play a major role in protecting hepatocytes from iron overload in chronic hemolysis. Copyright© Ferrata Storti Foundation.

Smartphone spectrometer for non-invasive diffuse reflectance spectroscopy based hemoglobin sensing (Conference Presentation)

NASA Astrophysics Data System (ADS)

Edwards, Perry S.

2016-10-01

Fiber-optic based diffuse reflectance spectroscopy (DRS) is shown to be a highly specific and highly sensitive method for non-invasive detection of various cancers (e.g. cervical and oral) as well as many other diseases. Fiber-optic DRS diagnosis relies on non-invasive biomarker detection (e.g. oxy- and deoxy-hemoglobin) and can be done without the need for sophisticated laboratory analysis of samples. Thus, it is highly amenable for clinical adoption especially in resource scarce regions that have limited access to such developed laboratory infrastructure. Despite the demonstrated effectiveness of fiber-optic DRS, such systems remain cost prohibitive in many of these regions, mainly due to the use of bulky and expensive spectrometers. Here, a fiber-optic DRS system is coupled to a smartphone spectrometer and is proposed as a low-cost solution for non-invasive tissue hemoglobin sensing. The performance of the system is assessed by measuring tissue phantoms with varying hemoglobin concentrations. A DRS retrieval algorithm is used to extract hemoglobin parameters from the measurements and determine the accuracy of the system. The results are then compared with those of a previously reported fiber-optic DRS system which is based on a larger more expensive spectrometer system. The preliminary results are encouraging and indicate the potential of the smartphone spectrometer as a viable low-cost option for non-invasive tissue hemoglobin sensing.

Augmented water binding and low cellular water content in erythrocytes of camel and camelids.

PubMed

Bogner, P; Csutora, P; Cameron, I L; Wheatley, D N; Miseta, A

1998-12-01

We investigated a link between hemoglobin primary structure, hemoglobin hydrophobicity-hydrophilicity, and erythrocyte water content in various mammalian species. Some hemoglobin molecules, particularly those of the camel and camelids, contain more charged amino acid residues and are more hydrophilic than the hemoglobins of human and a number of other mammalian species. To test the in vivo significance of these alterations of hemoglobin primary structure, we determined the osmotically unresponsive erythrocyte water fractions in mannit solutions of various osmolarities at 4 degreesC. Among the species investigated, the size of the osmotically unresponsive erythrocyte water fraction relates in a positive linear way to hemoglobin hydrophilicity. The extreme low total erythrocyte water content of camel erythrocytes (1.1-1.3 g water/g dry mass) may be explained by a comparatively high osmotically unresponsive erythrocyte water fraction. It is proposed that alterations of hemoglobin sequences of camel and camelids may be the part of a natural selection process aimed at protecting these animals against osmotic dehydration in arid environments.

Augmented water binding and low cellular water content in erythrocytes of camel and camelids.

PubMed Central

Bogner, P; Csutora, P; Cameron, I L; Wheatley, D N; Miseta, A

1998-01-01

We investigated a link between hemoglobin primary structure, hemoglobin hydrophobicity-hydrophilicity, and erythrocyte water content in various mammalian species. Some hemoglobin molecules, particularly those of the camel and camelids, contain more charged amino acid residues and are more hydrophilic than the hemoglobins of human and a number of other mammalian species. To test the in vivo significance of these alterations of hemoglobin primary structure, we determined the osmotically unresponsive erythrocyte water fractions in mannit solutions of various osmolarities at 4 degreesC. Among the species investigated, the size of the osmotically unresponsive erythrocyte water fraction relates in a positive linear way to hemoglobin hydrophilicity. The extreme low total erythrocyte water content of camel erythrocytes (1.1-1.3 g water/g dry mass) may be explained by a comparatively high osmotically unresponsive erythrocyte water fraction. It is proposed that alterations of hemoglobin sequences of camel and camelids may be the part of a natural selection process aimed at protecting these animals against osmotic dehydration in arid environments. PMID:9826628

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.

PubMed

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.

Association of subclinical inflammation, glycated hemoglobin and risk for obstructive sleep apnea syndrome.

PubMed

D'Aurea, Carolina Vicaria Rodrigues; Cerazi, Bruno Gion de Andrade; Laurinavicius, Antonio Gabriele; Janovsky, Carolina Castro Porto Silva; Conceição, Raquel Dilguerian de Oliveira; Santos, Raul D; Bittencourt, Márcio Sommer

2017-01-01

To investigate the inter-relation between high sensitivity C-reactive protein and glycated hemoglobin in prediction of risk of obstructive sleep apnea. We included all individuals participating in a check-up program at the Preventive Medicine Center of Hospital Israelita Albert Einstein in 2014. The Berlin questionnaire for risk of obstructive sleep apnea was used, and the high sensitivity C-reactive protein and glycated hemoglobin levels were evaluated. The sample included 7,115 participants (age 43.4±9.6 years, 24.4% women). The Berlin questionnaire showed changes in 434 (6.1%) individuals. This finding was associated with high sensitivity C-reactive protein and glycated hemoglobin levels (p<0.001). However, only the association between the Berlin questionnaire result and glycated hemoglobin remained significant in the adjusted multivariate analysis, for the traditional risk factors and for an additional model, including high-density lipoprotein cholesterol and triglycerides. The glycated hemoglobin, even below the threshold for diagnosis of diabetes, is independently associated with obstructive sleep apnea syndrome, even after adjustment for obesity and C-reactive protein. These findings suggest a possible pathophysiological link between changes in insulin resistance and obstructive sleep apnea syndrome, independently from obesity or low-grade inflammation. Investigar a inter-relação entre proteína C-reativa de alta sensibilidade e hemoglobina glicada na predição do risco de apneia obstrutiva do sono. Foram incluídos todos os indivíduos participantes do programa de check-up do Centro de Medicina Preventiva Hospital Israelita Albert Einstein em 2014. Foi aplicado o questionário de Berlin sobre risco de apneia do sono, e avaliadas as dosagens de hemoglobina glicada e proteína C-reativa de alta sensibilidade. Foram incluídos 7.115 participantes (idade 43,4±9,6 anos, 24,4% mulheres). A prevalência de alteração no questionário de Berlin foi de 434 (6,1%). A alteração do questionário de Berlin associou-se positivamente aos resultados da proteína C-reativa de alta sensibilidade e da hemoglobina glicada (p<0,001). No entanto, apenas a associação entre o resultado do questionário de Berlin e a hemoglobina glicada permaneceu significativa na análise multivariada ajustada tanto para fatores de risco tradicionais quanto para um modelo adicional, que incluiu também lipoproteína de alta densidade-colesterol (HDL-c) e triglicérides. A hemoglobina glicada, mesmo em valores abaixo do critério diagnóstico para diabetes mellitus, está associada de forma independente ao risco para síndrome da apneia obstrutiva do sono, mesmo após ajuste para obesidade e proteína C-reativa. Estes achados sugerem possível ligação fisiopatológica entre alterações na resistência insulínica e a síndrome da apneia obstrutiva do sono, que independe da obesidade ou inflamação de baixo grau.

Heart failure and diabetes: collateral benefit of chronic disease management.

PubMed

Ware, Molly G; Flavell, Carol M; Lewis, Eldrin F; Nohria, Anju; Warner-Stevenson, Lynne; Givertz, Michael M

2006-01-01

To test the hypothesis that a focus on heart failure (HF) care may be associated with inadequate diabetes care, the authors screened 78 patients (aged 64+/-11 years; 69% male) with diabetes enrolled in an HF disease management program for diabetes care as recommended by the American Diabetes Association (ADA). Ninety-five percent of patients had hemoglobin A1c levels measured within 12 months, and 71% monitored their glucose at least once daily. Most patients received counseling regarding diabetic diet and exercise, and approximately 80% reported receiving regular eye and foot examinations. Mean hemoglobin A1c level was 7.8+/-1.9%. There was no relationship between hemoglobin A1c levels and New York Heart Association class or history of HF hospitalizations. Contrary to the authors' hypothesis, patients in an HF disease management program demonstrated levels of diabetic care close to ADA goals. "Collateral benefit" of HF disease management may contribute to improved patient outcomes in diabetic patients with HF.

Hemoglobin levels and prevalence of anemia in pregnant women assisted in primary health care services, before and after fortification of flour.

PubMed

Araújo, Claudia Regina Marchiori Antunes; Uchimura, Taqueco Teruya; Fujimori, Elizabeth; Nishida, Fernanda Shizue; Veloso, Giovanna Batista Leite; Szarfarc, Sophia Cornblutz

2013-06-01

We evaluated hemoglobin-Hb levels and prevalence of anemia in pregnant women before and after fortification of flour. It was developed a study to evaluate intervention, of the type before and after, with independent population samples. Study was conducted in primary health care services in Maringá, PR. We assessed 366 and 419 medical records, Before and After implementation of fortification. Pregnant women with Hb < 11g/dL were considered anemic. Data were submitted to multiple linear regression analysis. There was low prevalence of anemia affecting 12.3% and 9.4% pregnant women Before and After fortification (p > 0.05), but the Group After the fortification had higher Hb levels (p < 0.05). Hb levels associated with Group, gestational age, previous pregnancy number, employment and marital status (p < 0.05). Although the fortification of flour may have had role in increasing the mean hemoglobin, we need consider the contribution of other variables not investigated.

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

PubMed

Inada, Shinya; Koga, Masafumi

2017-01-01

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

Identification of five genetic variants as novel determinants of type 2 diabetes mellitus in Japanese by exome-wide association studies.

PubMed

Yamada, Yoshiji; Sakuma, Jun; Takeuchi, Ichiro; Yasukochi, Yoshiki; Kato, Kimihiko; Oguri, Mitsutoshi; Fujimaki, Tetsuo; Horibe, Hideki; Muramatsu, Masaaki; Sawabe, Motoji; Fujiwara, Yoshinori; Taniguchi, Yu; Obuchi, Shuichi; Kawai, Hisashi; Shinkai, Shoji; Mori, Seijiro; Arai, Tomio; Tanaka, Masashi

2017-10-06

We performed exome-wide association studies to identify single nucleotide polymorphisms that either influence fasting plasma glucose level or blood hemoglobin A 1c content or confer susceptibility to type 2 diabetes mellitus in Japanese. Exome-wide association studies were performed with the use of Illumina Human Exome-12 DNA Analysis or Infinium Exome-24 BeadChip arrays and with 11,729 or 8635 subjects for fasting plasma glucose level or blood hemoglobin A 1c content, respectively, or with 14,023 subjects for type 2 diabetes mellitus (3573 cases, 10,450 controls). The relation of genotypes of 41,265 polymorphisms to fasting plasma glucose level or blood hemoglobin A 1c content was examined by linear regression analysis. After Bonferroni's correction, 41 and 17 polymorphisms were significantly ( P < 1.21 × 10 -6 ) associated with fasting plasma glucose level or blood hemoglobin A 1c content, respectively, with two polymorphisms (rs139421991, rs189305583) being associated with both. Examination of the relation of allele frequencies to type 2 diabetes mellitus with Fisher's exact test revealed that 87 polymorphisms were significantly ( P < 1.21 × 10 -6 ) associated with type 2 diabetes mellitus. Subsequent multivariable logistic regression analysis with adjustment for age and sex showed that four polymorphisms (rs138313632, rs76974938, rs139012426, rs147317864) were significantly ( P < 1.44 × 10 -4 ) associated with type 2 diabetes mellitus, with rs138313632 and rs139012426 also being associated with fasting plasma glucose and rs76974938 with blood hemoglobin A 1c . Five polymorphisms-rs139421991 of CAT , rs189305583 of PDCL2 , rs138313632 of RUFY1 , rs139012426 of LOC100505549 , and rs76974938 of C21orf59 -may be novel determinants of type 2 diabetes mellitus.

Balanced globin protein expression and heme biosynthesis improve production of human hemoglobin in Saccharomyces cerevisiae.

PubMed

Liu, Lifang; Martínez, José L; Liu, Zihe; Petranovic, Dina; Nielsen, Jens

2014-01-01

Due to limitations associated with whole blood for transfusions (antigen compatibility, transmission of infections, supply and storage), the use of cell-free hemoglobin as an oxygen carrier substitute has been in the center of research interest for decades. Human hemoglobin has previously been synthesized in yeast, however the challenge is to balance the expression of the two different globin subunits, as well as the supply of the prosthetic heme required for obtaining the active hemoglobin (α2β2). In this work we evaluated the expression of different combinations of α and β peptides and combined this with metabolic engineering of the heme biosynthetic pathway. Through evaluation of several different strategies we showed that engineering the biosynthesis pathway can substantially increase the heme level in yeast cells, and this resulted in a significant enhancement of human hemoglobin production. Besides demonstration of improved hemoglobin production our work demonstrates a novel strategy for improving the production of complex proteins, especially multimers with a prosthetic group. © 2013 Published by International Metabolic Engineering Society on behalf of International Metabolic Engineering Society.

Ethnically Tibetan women in Nepal with low hemoglobin concentration have better reproductive outcomes

PubMed Central

Cho, Jang Ik; Basnyat, Buddha; Jeong, Choongwon; Di Rienzo, Anna; Childs, Geoff; Craig, Sienna R.; Sun, Jiayang

2017-01-01

Abstract Background and objectives: Tibetans have distinctively low hemoglobin concentrations at high altitudes compared with visitors and Andean highlanders. This study hypothesized that natural selection favors an unelevated hemoglobin concentration among Tibetans. It considered nonheritable sociocultural factors affecting reproductive success and tested the hypotheses that a higher percent of oxygen saturation of hemoglobin (indicating less stress) or lower hemoglobin concentration (indicating dampened response) associated with higher lifetime reproductive success. Methodology: We sampled 1006 post-reproductive ethnically Tibetan women residing at 3000–4100 m in Nepal. We collected reproductive histories by interviews in native dialects and noninvasive physiological measurements. Regression analyses selected influential covariates of measures of reproductive success: the numbers of pregnancies, live births and children surviving to age 15. Results: Taking factors such as marriage status, age of first birth and access to health care into account, we found a higher percent of oxygen saturation associated weakly and an unelevated hemoglobin concentration associated strongly with better reproductive success. Women who lost all their pregnancies or all their live births had hemoglobin concentrations significantly higher than the sample mean. Elevated hemoglobin concentration associated with a lower probability a pregnancy progressed to a live birth. Conclusions and implications: These findings are consistent with the hypothesis that unelevated hemoglobin concentration is an adaptation shaped by natural selection resulting in the relatively low hemoglobin concentration of Tibetans compared with visitors and Andean highlanders. PMID:28567284

[Hemoglobin changes (Hb) in miners exposed to high altitude and associated factors].

PubMed

Mejia, Christian R; Quiñones-Laveriano, Dante M; Gomero, Raúl; Pérez-Pérez, Luis

To determine the variation of hemoglobin (Hb) in two groups of miners working at different altitudes. A longitudinal study conducted in a private company. Hb was obtained from entrance exams and annual checks of workers at two locations: at sea level and at Peruvian highlands (4,100 m), taken by trained staff and equipment calibrated to environmental conditions. We analyzed variations in the course of the years with the PA-GEE statistical test; p values were obtained. Of the 376 workers, 89% (322) were men, the median age was 32 years (range 20-57) and 84% (304) were at high altitude. In multivariate analysis, male sex (p < 0.001), body mass index (BMI; p = 0.021) and working at high altitude (p < 0.001) were associated with the greatest variation of Hb in time, adjusted for age, length, and type of work. These findings should be considered for health surveillance of workers exposed to similar conditions to prevent chronic mountain sickness. The change in Hb of miners was associated with male sex, BMI, and work at high altitude.

Once-Monthly Continuous Erythropoietin Receptor Activator (C.E.R.A.) in Patients with Hemodialysis-Dependent Chronic Kidney Disease: Pooled Data from Phase III Trials.

PubMed

Locatelli, Francesco; Choukroun, Gabriel; Truman, Matt; Wiggenhauser, Alfons; Fliser, Danilo

2016-04-01

Erythropoiesis-stimulating agents and iron are commonly used in patients with chronic kidney disease with the aim of correcting anemia and maintaining stable hemoglobin levels. We analyzed pooled data from 13 studies with similar designs included in the Umbrella Continuous Erythropoietin Receptor Activator (C.E.R.A.) program to investigate the effects of continuous erythropoiesis receptor activator in clinically relevant subgroups of patients with chronic kidney disease and to determine whether the efficacy and safety outcomes demonstrated in the overall chronic kidney disease population are maintained in specific subgroups. Data from 13 Phase III trials set up with similar design were retrospectively pooled for this analysis. Patients with chronic kidney disease who had previously been receiving epoetin or darbepoetin were switched to continuous erythropoiesis receptor activator once-monthly after a 4- to 8-week screening period. Patients entered a 16-week continuous erythropoiesis receptor activator dose-titration period followed by an 8-week evaluation period. In total, 2060 patients were included in the analysis. Subgroups were defined based on: hemoglobin target range [lower (10.0-12.0 g/dL)/upper (10.5-13.0 g/dL)], gender (female/male), age (<65/≥65), baseline N-terminal pro-B-type natriuretic peptide levels (<5000/≥5000), cardiovascular risk factors (diabetes/cardiac/vascular/none). Across all subgroups analyzed, switching from shorter-acting erythropoiesis-stimulating agents to continuous erythropoiesis receptor activator once-monthly maintained stable hemoglobin concentrations in a high proportion of patients (78%), with only moderate hemoglobin fluctuations and a low number of dose changes. The safety profile across subgroups was as expected based on pre-existing risk factors; observed increases in adverse events were attributable to underlying risk factors rather than study drug. This retrospective analysis of 13 trials showed that continuous erythropoiesis receptor activator once-monthly maintained stable hemoglobin levels across a number of clinically relevant patient subgroups, including those with higher inherent cardiovascular risk. The safety profile was consistent with that previously established in the chronic kidney disease population. CLINICALTRIALS. NCT00413894/NCT00545571/NCT00517413/NCT00560404/NCT00882713/NCT00550680/NCT00576303/NCT00660023/NCT00717821/NCT00642850/NCT00605293/NCT00661505/NCT00699348. F. Hoffmann-La Roche Ltd, Basel, Switzerland.

Association of anemia, child and family characteristics with elevated blood lead concentrations in preschool children from Montevideo, Uruguay.

PubMed

Queirolo, Elena I; Ettinger, Adrienne S; Stoltzfus, Rebecca J; Kordas, Katarzyna

2010-01-01

Elevated blood lead levels (BPbs) have been identified in Uruguayan children in the La Teja neighborhood of Montevideo, but the extent of lead exposure in other city areas is unknown. Sources and predictors of exposure also remain understudied in this population. In 2007, the authors screened lead and hemoglobin levels in capillary blood of 222 preschool children from several areas of Montevideo, Uruguay, and identified predictors of elevated BPbs. Mean BPb was 9.0 +/- 6.0 microg/dL and 32.9% of children had levels >or= 10microg/dL. Mean hemoglobin level was 10.5 +/- 1.5 g/dL, with 44.1% having levels <10.5g/dL. Older child age, hemoglobin <10.5g/dL, and putting fingers/toys in the mouth were associated with higher BPbs. Young maternal age, less education, father's job with potential risk of lead exposure, and fewer family possessions were also associated with higher BPbs. Pediatric lead exposure is a public health problem in Uruguay, with children experiencing elevated BPbs at a young age.

A hospital policy change toward delayed cord clamping is effective in improving hemoglobin levels and anemia status of 8-month-old Peruvian infants.

PubMed

Gyorkos, Theresa W; Maheu-Giroux, Mathieu; Blouin, Brittany; Creed-Kanashiro, Hilary; Casapía, Martín; Aguilar, Eder; Silva, Hermánn; Joseph, Serene A; Penny, Mary E

2012-12-01

To assess the effectiveness of a hospital policy change toward delayed cord clamping on infant hemoglobin (Hb) levels and anemia status at 4 and 8 months of age. A cohort of Peruvian mothers and infants, originating from a pre/post study investigating a change in hospital policy from early to delayed cord clamping, was followed until 8 months postpartum. Infant hemoglobin levels and anemia status were measured at 4 and 8 months postpartum. Following the hospital policy change, adjusted mean infant Hb levels improved by 0.89 gdl(-1) [95% confidence interval (95% CI) 0.57-1.22] and anemia was significantly reduced (aOR = 0.38; 95% CI 0.19-0.78) at 8 months postpartum. A hospital policy change toward delayed cord clamping is effective in improving Hb levels and the anemia status of 8-month-old infants. Prior to scaling-up this intervention, issues related to training, monitoring, safety, additional long-term benefits and specific local conditions should be investigated.

CD73 and AMPD3 deficiency enhance metabolic performance via erythrocyte ATP that decreases hemoglobin oxygen affinity.

PubMed

O'Brien, William G; Berka, Vladimir; Tsai, Ah-Lim; Zhao, Zhaoyang; Lee, Cheng Chi

2015-08-07

Erythrocytes are the key target in 5'-AMP induced hypometabolism. To understand how regulation of endogenous erythrocyte AMP levels modulates systemic metabolism, we generated mice deficient in both CD73 and AMPD3, the key catabolic enzymes for extracellular and intra-erythrocyte AMP, respectively. Under physiological conditions, these mice displayed enhanced capacity for physical activity accompanied by significantly higher food and oxygen consumption, compared to wild type mice. Erythrocytes from Ampd3(-/-) mice exhibited higher half-saturation pressure of oxygen (p50) and about 3-fold higher levels of ATP and ADP, while they maintained normal 2,3-bisphosphoglycerate (2,3-BPG), methemoglobin levels and intracellular pH. The affinity of mammalian hemoglobin for oxygen is thought to be regulated primarily by 2,3-BPG levels and pH (the Bohr effect). However, our results show that increased endogenous levels of ATP and ADP, but not AMP, directly increase the p50 value of hemoglobin. Additionally, the rise in erythrocyte p50 directly correlates with an enhanced capability of systemic metabolism.

Parvovirus B19 in anemic liver transplant recipients.

PubMed Central

Ndimbie, O K; Frezza, E; Jordan, J A; Koch, W; van Thiel, D H

1996-01-01

Five hundred thirty-three liver transplant recipients were seen for follow-up care over a 6-month period. Of these, 23 (4.3%) had a hemoglobin level of < or = 9 g/dl, with 19 being eligible for inclusion in this study. The median hemoglobin level was 8.7 g/dl. Two patients had iron-deficiency anemia. All of the patients were on therapeutic drugs which can suppress erythropoiesis or shorten the lifespan of mature erythrocytes. Six patients (31.6%) were viremic for human parvovirus B19 but none was B19 immunoglobulin M seropositive. Two patients were immunoglobulin M seropositive for cytomegalovirus. The patients with circulating B19 DNA were not easily distinguished from those without the virus by their laboratory results. The absence of reticulocyte counts for these patients contributed to this inability to differentiate B19 from other causes of anemia, particularly drug myelotoxicity. The high likelihood of making a specific diagnosis with the increasing availability of PCR should spur the search for this virus in the liver transplant population. PMID:8914771

Hydroxyurea therapy of a murine model of sickle cell anemia inhibits the progression of pneumococcal disease by down-modulating E-selectin

PubMed Central

Lebensburger, Jeffrey D.; Howard, Thad; Hu, Yunming; Pestina, Tamara I.; Gao, Geli; Johnson, Melissa; Zakharenko, Stanislav S.; Ware, Russell E.; Tuomanen, Elaine I.; Persons, Derek A.

2012-01-01

Sickle cell anemia is characterized by chronic hemolysis coupled with extensive vascular inflammation. This inflammatory state also mechanistically promotes a high risk of lethal, invasive pneumococcal infection. Current treatments to reduce vaso-occlusive complications include chronic hydroxyurea therapy to induce fetal hemoglobin. Because hydroxyurea also reduces leukocytosis, an understanding of the impact of this treatment on pneumococcal pathogenesis is needed. Using a sickle cell mouse model of pneumococcal pneumonia and sepsis, administration of hydroxyurea was found to significantly improve survival. Hydroxyurea treatment decreased neutrophil extravasation into the infected lung coincident with significantly reduced levels of E-selectin in serum and on pulmonary epithelia. The protective effect of hydroxyurea was abrogated in mice deficient in E-selectin. The decrease in E-selectin levels was also evident in human sickle cell patients receiving hydroxyurea therapy. These data indicate that in addition to induction of fetal hemoglobin, hydroxyurea attenuates leukocyte–endothelial interactions in sickle cell anemia, resulting in protection against lethal pneumococcal sepsis. PMID:22130804

[Regulation of the β-globin gene family expression, useful in the search for new therapeutic targets for hemoglobinopathies].

PubMed

Scheps, Karen G; Varela, Viviana

Different hemoglobin isoforms are expressed during the embryonic, fetal and postnatal stages. They are formed by combination of polypeptide chains synthesized from the α- and β-globin gene clusters. Based on the fact that the presence of high hemoglobin F levels is beneficial in both sickle cell disease and severe thalassemic syndromes, a revision of the regulation of the β-globin cluster expression is proposed, especially regarding the genes encoding the y-globin chains (HBG1 and HBG2). In this review we describe the current knowledge about transcription factors and epigenetic regulators involved in the switches of the β-globin cluster. It is expected that the consolidation of knowledge in this field will allow finding new therapeutic targets for the treatment of hemoglobinopathies.

Iron-Chelating Therapy for Transfusional Iron Overload

PubMed Central

Brittenham, Gary M.

2011-01-01

A 16-year-old boy with sickle cell anemia undergoes routine screening with transcranial Doppler ultrasonography to assess the risk of stroke. This examination shows an abnormally elevated blood-flow velocity in the middle cerebral artery. The hemoglobin level is 7.2 g per deciliter, the reticulocyte count is 12.5%, and the fetal hemoglobin level is 8.0%. Long-term treatment with red-cell transfusion is initiated to prevent stroke. A hematologist recommends prophylactic iron-chelating therapy. PMID:21226580

Albumin, Hemoglobin, and the Trajectory of Cognitive Function in Community-Dwelling Older Japanese: A 13-Year Longitudinal Study.

PubMed

Murayama, H; Shinkai, S; Nishi, M; Taniguchi, Y; Amano, H; Seino, S; Yokoyama, Y; Yoshida, H; Fujiwara, Y; Ito, H

2017-01-01

Cognitive function can substantially decline over a long period, and understanding the trajectory of cognitive function is important. However, little is known about the linkage between nutritional biomarkers and long-term cognitive change. We analyzed 13-year longitudinal data for older Japanese to examine the associations of serum albumin and hemoglobin levels with the trajectory of cognitive function. Longitudinal study. Community-based. A total of 1,744 community-dwelling adults aged 65 years or older who participated in annual health examinations in Kusatsu town, Gunma Prefecture, Japan, from 2002-2014. Cognitive function was assessed annually by the Mini-Mental State Examination (MMSE). Albumin and hemoglobin levels at baseline (the year when a respondent first participated in the health examination) were divided into quartiles. Hierarchical linear modeling was used to analyze intrapersonal and interpersonal differences in cognitive function. Participants' MMSE scores decreased at an accelerated rate over the 13-year period. Participants with the lowest baseline albumin level (below the first quartile line) showed a greater accelerated decline in MMSE scores over time, compared with those with the highest level (above the third quartile line). Moreover, MMSE scores in participants with a lower hemoglobin level and lower MMSE score at baseline tended to decline faster over time at an accelerated rate. These findings yield new insights about the complex and diverse roles of these nutritional biomarkers on the trajectory of cognitive function in old age.

Body Growth and Rapid Hematological Development Support Breath Hold of Baby Belugas (Delphinapterus leucas) during Subice Transit.

PubMed

Noren, Shawn R; Poll, Caryn P; Edwards, Matthew S

Body size and oxygen stores in the blood and muscle set breath-hold limits in marine mammals, yet these characteristics are understudied in immature cetaceans. We examined body mass and hematology from birth through adulthood in beluga whales (Delphinapterus leucas). At birth, body mass was 8% and 6% of the maximum mass recorded for adult females and males, respectively. Body mass then increased rapidly, approaching an asymptote around 12 yr for females and 18 yr for males. Interestingly, red blood cell counts, hemoglobin content, and hematocrit levels decreased after birth; this neonatal anemia was reversed as levels increased after 2 mo postpartum. Mature levels were obtained at approximately 8, 9, and 11 mo postpartum, respectively. Neonatal mean corpuscular hemoglobin also increased with ontogeny; mature levels were achieved by approximately 13 mo after birth. In contrast, mean corpuscular volume and mean corpuscular hemoglobin concentration demonstrated a significant but subtle increase throughout ontogeny. Our results indicate that postnatal maturation was required and that maturation occurred far earlier than the age at weaning (i.e., 2-3 yr postpartum). This is atypical of marine mammals, which generally achieve mature hemoglobin levels at weaning. Hematological maturation before maternal independence undoubtedly supports the prolonged breath holds of young belugas transiting under sea ice. This assessment enhances our knowledge of cetacean physiology and provides important inputs for determining age-specific dive capacity, yielding insights into age-specific flexibility to alter underwater behaviors, as will be required for future regime shifts and disturbances.

Theoretical model for optical oximetry at the capillary level: exploring hemoglobin oxygen saturation through backscattering of single red blood cells

NASA Astrophysics Data System (ADS)

Liu, Rongrong; Spicer, Graham; Chen, Siyu; Zhang, Hao F.; Yi, Ji; Backman, Vadim

2017-02-01

Oxygen saturation (sO2) of red blood cells (RBCs) in capillaries can indirectly assess local tissue oxygenation and metabolic function. For example, the altered retinal oxygenation in diabetic retinopathy and local hypoxia during tumor development in cancer are reflected by abnormal sO2 of local capillary networks. However, it is far from clear whether accurate label-free optical oximetry (i.e., measuring hemoglobin sO2) is feasible from dispersed RBCs at the single capillary level. The sO2-dependent hemoglobin absorption contrast present in optical scattering signal is complicated by geometry-dependent scattering from RBCs. We present a numerical study of backscattering spectra from single RBCs based on the first-order Born approximation, considering practical factors: RBC orientations, size variation, and deformations. We show that the oscillatory spectral behavior of RBC geometries is smoothed by variations in cell size and orientation, resulting in clear sO2-dependent spectral contrast. In addition, this spectral contrast persists with different mean cellular hemoglobin content and different deformations of RBCs. This study shows for the first time the feasibility of, and provides a theoretical model for, label-free optical oximetry at the single capillary level using backscattering-based imaging modalities, challenging the popular view that such measurements are impossible at the single capillary level.

Test-retest assessment of functional near-infrared spectroscopy to measure risk decision making in young adults

NASA Astrophysics Data System (ADS)

Li, Lin; Lin, Zijing; Cazzell, Mary; Liu, Hanli

2013-03-01

Investigation of the reliability and reproducibility of the hemodynamic response is important for interpretation and understanding of the results of functional near-infrared spectroscopy (fNIRS). It measures optical signals absorbed by the brain tissue and reflects the neuronal activities indirectly. Here we described an fNIRS study measured in the prefrontal region (Brodman area 9, 10, part of 46)to examine the risk decision-making behavior in nine young adults. The Balloon Analog Risk Task (BART) is widely used to test the level of risk taking ability in the field of psychology. BART was a protocol utilized in this study to evoke a risk-taking environment with a gambling-like balloon game in each subject. Specifically, we recorded the brain oxygenated-hemoglobin (HbO) and deoxygenated-hemoglobin (HHb) changes during the two repeated measurements within a time interval of 3 weeks. The results demonstrate that the changes in HbO2 amplitudes have high reliability at the group level, and that the spatial patterns of the tomographic images have high reproducibility in size and a moderate degree of overlap. Overall, this study confirms that the hemodynamic response to risk decision-making (i.e., BART) seen by fNIRS is highly reliable and reproducible.

Middle cerebral artery peak systolic velocity to predict fetal hemoglobin levels in twin anemia-polycythemia sequence.

PubMed

Slaghekke, F; Pasman, S; Veujoz, M; Middeldorp, J M; Lewi, L; Devlieger, R; Favre, R; Lopriore, E; Oepkes, D

2015-10-01

To evaluate the diagnostic accuracy of middle cerebral artery peak systolic velocity (MCA-PSV) Doppler measurements in prediction of hemoglobin levels in twin anemia-polycythemia sequence (TAPS). This study involved a consecutive cohort comprising monochorionic twin pregnancies complicated by TAPS managed at three European fetal medicine centers between 2005 and 2013. The accuracy of MCA-PSV, measured immediately prior to fetal hemoglobin (Hb) measurement by fetal or cord blood sampling, for prediction of anemia and polycythemia was assessed using 2 × 2 tables. A total of 116 measurements (74 recorded in donors and 42 in recipients) from 43 twin pregnancies complicated by TAPS were available for analysis. MCA-PSV multiples of the median (MoM) values correlated well with Hb levels (r = - 0.86; P < 0.001). The sensitivity of MCA-PSV ≥ 1.5 MoM to predict severe anemia (Hb deficit > 5 SD below the mean) in TAPS donors was 94% (95% CI, 85-98%); specificity was 74% (95% CI, 62-83%); positive and negative predictive values were 76% (95% CI, 65-85%) and 94% (95% CI, 83-98%), respectively. The sensitivity of MCA-PSV ≤ 1.0 MoM to predict polycythemia (Hb level > 5 SD above the mean) in TAPS recipients was 97% (95% CI, 87-99%); specificity was 96% (95% CI, 89-99%); positive and negative predictive values were 93% (95% CI, 81-97%) and 99% (95% CI, 93-100%), respectively. MCA-PSV measurement has high diagnostic accuracy for predicting abnormal Hb levels in fetuses with TAPS. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

Copper and the oxidation of hemoglobin: a comparison of horse and human hemoglobins.

PubMed

Rifkind, J M; Lauer, L D; Chiang, S C; Li, N C

1976-11-30

Oxidation studies of hemoglobin by Cu(II) indicate that for horse hemoglobin, up to a Cu(II)/heme molar ratio of 0.5, all of the Cu(II) added is used to rapidly oxidize the heme. On the other hand, most of the Cu(II) added to human hemoglobin at low Cu(II)/heme molar ratios is unable to oxidize the heme. Only at Cu(II)/heme molar ratios greater than 0.5 does the amount of oxidation per added Cu(II) approach that of horse hemoglobin. At the same time, binding studies indicate that human hemoglobin has an additional binding site involving one copper for every two hemes, which has a higher copper affinity than the single horse hemoglobin binding site. The Cu(II) oxidation of human hemoglobin is explained utilizing this additional binding site by a mechanism where a transfer of electrons cannot occur between the heme and the Cu(II) bound to the high affinity human binding site. The electron transfer must involve the Cu(II) bound to the lower affinity human hemoglobin binding site, which is similar to the only horse hemoglobin site. The involvement of beta-2 histidine in the binding of this additional copper is indicated by a comparison of the amino acid sequences of various hemoglobins which possess the additional site, with the amino acid sequences of hemoglobins which do not possess the additional site. Zn(II), Hg(II), and N-ethylmaleimide (NEM) are found to decrease the Cu(II) oxidation of hemoglobin. The sulfhydryl reagents, Hg(II) and NEM, produce a very dramatic decrease in the rate of oxidation, which can only be explained by an effect on the rate for the actual transfer of electrons between the Cu(II) and the Fe(II). The effect of Zn(II) is much smaller and can, for the most part, be explained by the increased oxygen affinity, which affects the ligand dissociation process that must precede the electron transfer process.

Prenatal diagnosis of hemoglobinopathies: evaluation of techniques for analysing globin-chain synthesis in blood samples obtained by fetoscopy.

PubMed Central

Congote, L. F.; Hamilton, E. F.; Chow, J. C.; Perry, T. B.

1982-01-01

Three techniques for analysing hemoglobin synthesis in blood samples obtained by fetoscopy were evaluated. Of the fetuses studied, 12 were not at risk of genetic disorders, 10 were at risk of beta-thalassemia, 2 were at risk of sickle cell anemia and 1 was at risk of both diseases. The conventional method of prenatal diagnosis of hemoglobinopathies, involving the separation of globin chains labelled with a radioactive isotope on carboxymethyl cellulose (CMC) columns, was compared with a method involving globin-chain separation by high-pressure liquid chromatography (HPLC) and with direct analysis of labelled hemoglobin tetramers obtained from cell lysates by chromatography on ion-exchange columns. The last method is technically the simplest and can be used for diagnosing beta-thalassemia and sickle cell anemia. However, it gives spuriously high levels of adult hemoglobin in samples containing nonlabelled adult hemoglobin. HPLC is the fastest method for prenatal diagnosis of beta-thalassemia and may prove as reliable as the CMC method. Of the 13 fetuses at risk for hemoglobinopathies, 1 was predicted to be affected, and the diagnosis was confirmed in the abortus. Of 12 predicted to be unaffected, 1 was aborted spontaneously and was unavailable for confirmatory studies, as were 3 of the infants; however, the diagnosis was confirmed in seven cases and is awaiting confirmation when the infant in 6 months old in one case. Couples at risk of bearing a child with a hemoglobinopathy should be referred for genetic counselling before pregnancy or, at the latest, by the 12th week of gestation so that prenatal diagnosis can be attempted by amniocentesis, safer procedure, with restriction endonuclease analysis of the amniotic fluid cells. PMID:7139502

[The modification of structural and functional properties of human hemoglobin induced by nitroglycerin under different oxygen regime conditions].

PubMed

Artyukhov, V G; Kalaeva, E A; Putintseva, O V; Polyubez'eva, A I

2016-03-01

Human oxyhemoglobin exhibits high resistance to nitroglycerin during incubation of the protein with this compound for 0.3-3 h. Prolonged exposure (24 h) leads to activation of methemoglobin production. In the presence of nitroglycerin hemoglobin molecules undergo rapid oxidation during deoxygenation with formation of methemoglobin as the terminal product of human oxyhemoglobin interaction with nitroglycerin. The scheme of interaction processes of oxyhemoglobin with nitroglycerin in different conditions of oxygen regime is proposed. Partially deliganded hemoglobin plays the leading role in the initiation of hemoglobin oxidation processes.

Pseudopolycythemia, pseudothrombocytopenia, and pseudoleukopenia due to overfilling of blood collection vacuum tubes.

PubMed

Pewarchuk, W; VanderBoom, J; Blajchman, M A

1992-01-01

A patient blood sample with an unexpectedly high hemoglobin level, high hematocrit, low white blood cell count, and low platelet count was recognized as being spurious based on previously available data. Repeated testing of the original sample showed a gradual return of all parameters to expected levels. We provide evidence that the overfilling of blood collection vacuum tubes can lead to inadequate sample mixing and that, in combination with the settling of the cellular contents in the collection tubes, can result in spuriously abnormal hematological parameters as estimated by an automated method.

Staphylococcus aureus Growth using Human Hemoglobin as an Iron Source

PubMed Central

Pishchany, Gleb; Haley, Kathryn P.; Skaar, Eric P.

2013-01-01

S. aureus is a pathogenic bacterium that requires iron to carry out vital metabolic functions and cause disease. The most abundant reservoir of iron inside the human host is heme, which is the cofactor of hemoglobin. To acquire iron from hemoglobin, S. aureus utilizes an elaborate system known as the iron-regulated surface determinant (Isd) system1. Components of the Isd system first bind host hemoglobin, then extract and import heme, and finally liberate iron from heme in the bacterial cytoplasm2,3. This pathway has been dissected through numerous in vitro studies4-9. Further, the contribution of the Isd system to infection has been repeatedly demonstrated in mouse models8,10-14. Establishing the contribution of the Isd system to hemoglobin-derived iron acquisition and growth has proven to be more challenging. Growth assays using hemoglobin as a sole iron source are complicated by the instability of commercially available hemoglobin, contaminating free iron in the growth medium, and toxicity associated with iron chelators. Here we present a method that overcomes these limitations. High quality hemoglobin is prepared from fresh blood and is stored in liquid nitrogen. Purified hemoglobin is supplemented into iron-deplete medium mimicking the iron-poor environment encountered by pathogens inside the vertebrate host. By starving S. aureus of free iron and supplementing with a minimally manipulated form of hemoglobin we induce growth in a manner that is entirely dependent on the ability to bind hemoglobin, extract heme, pass heme through the bacterial cell envelope and degrade heme in the cytoplasm. This assay will be useful for researchers seeking to elucidate the mechanisms of hemoglobin-/heme-derived iron acquisition in S. aureus and possibly other bacterial pathogens. PMID:23426144

Erythrocyte creatine as a marker of intravascular hemolysis due to left ventricular outflow tract obstruction in hypertrophic cardiomyopathy.

PubMed

Kubo, Toru; Okumiya, Toshika; Baba, Yuichi; Hirota, Takayoshi; Tanioka, Katsutoshi; Yamasaki, Naohito; Sugiura, Tetsuro; Doi, Yoshinori L; Kitaoka, Hiroaki

2016-03-01

Erythrocyte creatine, a marker of erythrocyte age that increases with shortening of erythrocyte survival, has been reported to be a quantitative and reliable marker for intravascular hemolysis. We hypothesized that hemolysis could also occur due to intraventricular obstruction in patients with hypertrophic cardiomyopathy (HCM). The purpose of this study was to examine the presence of subclinical hemolysis and the relation between intravascular hemolysis and intraventricular pressure gradient (IVPG). We measured erythrocyte creatine in 92 HCM patients. Twelve patients had left ventricular outflow tract obstruction (LVOTO), 4 had midventricular obstruction (MVO), and the remaining 76 were non-obstructive. Erythrocyte creatine levels ranged from 0.92 to 4.36μmol/g hemoglobin. Higher levels of erythrocyte creatine were associated with higher IVPG (r=0.437, p<0.001). If erythrocyte creatine levels are high (≥1.8μmol/g hemoglobin), subclinical hemolysis is considered to be present. Half of LVOTO patients and no MVO patients showed high erythrocyte creatine levels. Although non-obstructive patients did not show significant intraventricular obstruction at rest, some showed high erythrocyte creatine levels. When LVOT-PG was measured during the strain phase of the Valsalva maneuver in 20 non-obstructive patients, 7 of those 20 patients showed LVOTO. In the 20 patients, there was no relation between erythrocyte creatine levels and LVOT-PG before the Valsalva maneuver (r=0.125, p=0.600), whereas there was a significant correlation between erythrocyte creatine and LVOT-PG provoked by the Valsalva maneuver (r=0.695, p=0.001). There is biochemical evidence of subclinical hemolysis in patients with HCM, and this hemolysis seems to be associated with LVOTO provoked by daily physical activities. Copyright © 2015 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

Evaluating the capacity to generate and preserve nitric oxide bioactivity in highly purified earthworm erythrocruorin: a giant polymeric hemoglobin with potential blood substitute properties.

PubMed

Roche, Camille J; Talwar, Abhinav; Palmer, Andre F; Cabrales, Pedro; Gerfen, Gary; Friedman, Joel M

2015-01-02

The giant extracellular hemoglobin (erythrocruorin) from the earth worm (Lumbricus terrestris) has shown promise as a potential hemoglobin-based oxygen carrier (HBOC) in in vivo animal studies. An important beneficial characteristic of this hemoglobin (LtHb) is the large number of heme-based oxygen transport sites that helps overcome issues of osmotic stress when attempting to provide enough material for efficient oxygen delivery. A potentially important additional property is the capacity of the HBOC either to generate nitric oxide (NO) or to preserve NO bioactivity to compensate for decreased levels of NO in the circulation. The present study compares the NO-generating and NO bioactivity-preserving capability of LtHb with that of human adult hemoglobin (HbA) through several reactions including the nitrite reductase, reductive nitrosylation, and still controversial nitrite anhydrase reactions. An assignment of a heme-bound dinitrogen trioxide as the stable intermediate associated with the nitrite anhydrase reaction in both LtHb and HbA is supported based on functional and EPR spectroscopic studies. The role of the redox potential as a factor contributing to the NO-generating activity of these two proteins is evaluated. The results show that LtHb undergoes the same reactions as HbA and that the reduced efficacy for these reactions for LtHb relative to HbA is consistent with the much higher redox potential of LtHb. Evidence of functional heterogeneity in LtHb is explained in terms of the large difference in the redox potential of the isolated subunits. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Comparison of hemostatic matrix and standard hemostasis in patients undergoing primary TKA.

PubMed

Comadoll, James L; Comadoll, Shea; Hutchcraft, Audrey; Krishnan, Sangeeta; Farrell, Kelly; Kreuwel, Huub T C; Bechter, Mark

2012-06-01

Bleeding after total knee arthroplasty increases the risk of pain, delayed rehabilitation, blood transfusion, and transfusion-associated complications. The authors compared pre- and postoperative decreases in hemoglobin as a surrogate for blood loss in consecutive patients treated at a single institution by the same surgeon (J.L.C.) using conventional hemostatic methods (electrocautery, suturing, or manual compression) or a gelatin and thrombin-based hemostatic matrix during total knee arthroplasty. Data were collected retrospectively by chart review. The population comprised 165 controls and 184 patients treated with hemostatic matrix. Median age was 66 years (range, 28-89 years); 66% were women. The arithmetic mean ± SD for the maximal postoperative decrease in hemoglobin was 3.18 ± 0.94 g/dL for controls and 2.19 ± 0.83 g/dL for the hemostatic matrix group. Least squares means estimates of the group difference (controls-hemostatic matrix) in the maximal decrease in hemoglobin was 0.96 g/dL (95% confidence interval, 0.77-1.14 mg/dL; P<.0001). Statistically significant covariate effects were observed for preoperative hemoglobin level (P<.0001) and body mass index (P=.0029). Transfusions were infrequent in both groups. The frequency of acceptable range of motion was high (control, 88%; hemostatic matrix, 84%). In both groups, overall mean tourniquet time was approximately 1 hour, and the most common length of stay was 3 to 5 days. No serious complications related to the hemostatic agent were observed. These data demonstrate that the use of a flowable hemostatic matrix results in less reduction in hemoglobin than the use of conventional hemostatic methods in patient undergoing total knee arthroplasty. Copyright 2012, SLACK Incorporated.

Risk factors associated with hypogonadism in β-thalassemia major patients: predictors for a frequent complication of a rare disease.

PubMed

Albu, Alice; Barbu, Carmen Gabriela; Antonie, Lavinia; Vladareanu, Florentina; Fica, Simona

2014-09-01

β-Thalassemia major (BTM) is a rare disease that challenges clinicians because of the high prevalence of complications despite progress in the development of new therapeutic methods. The aim of this study was to identify clinical and hematological parameters associated with hypogonadism, the most frequent iron overload-related complication found in Romanian patients. Patients with BTM were evaluated in the Endocrinology Department of Elias Hospital between February 2004 and December 2013. Only patients who provided written informed consent were included in the study. A complete physical and hormonal evaluation was performed on all patients, and data regarding treatment of the hematological disease were collected. Of the evaluable patients, 85 were included in the study (median age, 21[10] years; range, 13-36 years). We found that 30.6% of the study participants (26 of 85) had normal gonadal status, 54.1% (46 of 85) had early forms of hypogonadism (delayed or arrested puberty), and 15.3% (n = 13) developed hypogonadism after complete sexual maturation. Patients with any form of hypogonadism were older (median age 22 vs 16.5 years, P = 0.047), had significantly lower average hemoglobin levels (P = 0.003), and had higher levels of serum ferritin (P = 0.006) versus patients without hypogonadism. Patients with delayed puberty were associated with increased average serum ferritin levels (P = 0.007), decreased hemoglobin levels (P = 0.001), and increased age at initiation of iron chelation therapy (P < 0.01). We found no significant differences between patients with early forms of hypogonadism and those with hypogonadism after complete sexual maturation, with respect to the analyzed parameters. Patients with adult hypogonadism were significantly older (median age 26 vs 16.5 years, P = 0.007) and tended to have higher serum ferritin levels (P = 0.056) compared with patients without hypogonadism. Our data show that hypogonadism is highly prevalent among Romanian patients with BTM, its presence being associated with higher iron overload and lower hemoglobin values. The late start of iron chelation therapy was particularly associated with pubertal abnormalities.

Rice (Oryza) hemoglobins

USDA-ARS?s Scientific Manuscript database

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...

Human hemoglobin structural and functional alterations and heme degradation upon interaction with benzene: A spectroscopic study.

PubMed

Hosseinzadeh, Reza; Moosavi-Movahedi, Ali Akbar

2016-03-15

Here, the effect of benzene on hemoglobin structure, stability and heme prosthetic group integrity was studied by different methods. These included UV-vis absorption spectrophotometry, normal and synchronous fluorescence techniques, and differential scanning calorimetry (DSC). Our results indicated that benzene has high hemolytic potential even at low concentrations. The UV-vis spectroscopic results demonstrated that benzene altered both the globin chain and the heme prosthetic group of hemoglobin increasing met- and deoxy-Hb, while decreasing oxy-Hb. However, with increasing benzene the concentration of all species decreased due to heme destruction. The spectrophotometric results show that benzene has a high potential for penetrating the hydrophobic pocket of hemoglobin. These results were consistent with the molecular docking simulation results of benzene-hHb. Aggregation and thermal denaturation studies show that the increased benzene concentration induced hemoglobin aggregation with a decrease in stability, which is consistent with the DSC results. Conventional fluorescence spectroscopy revealed that the heme degradation species were produced in the presence of benzene. The results of constant wavelength synchronous fluorescence spectroscopy (CWSFS) indicated that at least five heme-degraded species were produced. Together, our results indicated that benzene has adverse effects on hemoglobin structure and function, and heme degradation. Copyright © 2015 Elsevier B.V. All rights reserved.

Hemoglobin switching in sheep and goats. VI. Commitment of erythroid colony-forming cells to the synthesis of betaC globin

PubMed Central

1976-01-01

Bone marrow from mature goats and sheep was cultured in plasma clots, and three erythropoietin (ESF)-dependent responses-growth (colony formation), differentiation (globin production), and initiation of hemoglobin C (alpha2beta2C) synthesis--were quantitated. ESF concentrations below 0.01 U/ml supported colony growth and adult hemoglobin production in cultures of goat marrow, while maximal hemoglobin C synthesis (70%), as measured between 72 and 96 h in culture, required a 100-fold higher ESF concentration. Sheep marrow was cultured in a medium enriched to enhance growth and to permit complete maturation of colonies. These colonies active in hemoglobin synthesis between 24 and 96 h produced mainly adult hemoglobin, and only between 96 and 120 h did sheep colonies develop which produced mainly hemoglobin C (up to 70%). A similar heterogeneity may exist among goat colonies. Thus, when goat bone marrow was fractionated by unit gravity sedimentation, more hemoglobin C synthesis was observed in colonies derived from cells of intermediate sedimentation velocity than in colonies derived from the most rapidly sedimenting cells. Brief exposure of sheep (in vivo) and goat (in vitro) bone marrow to a high ESF concentration committed precursor cells to the generation of colonies which, even at low ESF concentration, produced hemoglobin C. Committment to hemoglobin phenotype appears to be an early and probably irreversible event in the development of an erythroid cell. PMID:993267

[Prevalence of hemoglobinopathies in pregnant women in the Lanzarote health sanitary area].

PubMed

Calvo-Villas, J M; Zapata Ramos, M F; Cuesta Tovar, J; de la Iglesia Iñigo, S; Ropero Gradilla, P; Carreter de Granda, E; Sicilia Guillén, F

2006-05-01

The aim of this study is to analyze the global prevalence of carriers of heterozygous hemoglobinopathies among pregnant women settled in Lanzarote. A epidemiologic cross-sectional observational investigation was undertaken to study the prevalence of hemoglobinopathies in 2,436 pregnant women in Lanzarote. The techniques of primary screening were hemoglobin electrophoresis on cellulose acetate at alkaline pH for the detection of hemoglobin variants, and the quantification of HbA2 and HbF for the diagnosis of b thalassemia trait. The study to confirm the diagnosis of structural hemoglobinopathies was based on hemoglobin electrophoresis on citrate agar at acid pH, isolectric focusing and high-performance liquid chromatography (HPLC). The molecular characterization of b thalassemia trait (HbA2 >3.5%) was carried out by techniques using a real time PCR procedure with specific fluorescently labelled hybridization probes and allele-specific amplification (PCR-ARMS). The global prevalence of hemoglobinopathies was 11.90 corresponding to 9.44 for structural hemoglobinopathies and 2.46 for heterozygous b thalassemias. A variant hemoglobin was detected on 23 women and the distribution was as follows: thirteen carriers of hemoglobin S, seven HbC trait, two HbD trait and one "unstable" hemoglobin. 82.6% of the variant hemoglobins found were from migrant population from Africa and America. The high prevalence of carriers of structural hemoglobinopathies in Lanzarote justifies the initiation of programs for screening for hemoglobinopathies to prevent the emergence of severe states causing disease.

Fasting serum glucose and glycosylated hemoglobin level in obesity.

PubMed

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 <0.001) for 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 correlation between BMI with fasting serum glucose and glycosylated hemoglobin emphasizes the importance of maintenance of normal BMI to prevent early onset of type 2 diabetes mellitus.

Quantification of tissue oxygenation levels using diffuse reflectance spectroscopy

NASA Astrophysics Data System (ADS)

B. S., Suresh Anand; N., Sujatha

2011-08-01

Tumor growth is characterized by increased metabolic activity. The light absorption profile of hemoglobin in dysplastic tissue is different from a normal tissue. Neovascularization is a hallmark of many diseases and can serve as a predictive biomarker for the detection of cancers. Spectroscopic techniques can provide information about the metabolic and morphological changes related to the progression of neoplasia. Diffuse reflectance spectroscopy (DRS) measures the absorption and scattering properties of a biological tissue and this method can provide clinically useful information for the early diagnosis of epithelial precancers. We used tissue simulating phantoms with absorbing and scattering molecules for the determination of total hemoglobin concentration, hemoglobin oxygen saturation and intensity difference between the deoxy and oxy hemoglobin bands. The results show promising approach for the differentiating normal and malignant states of a tissue.

Liberal or restrictive transfusion in high-risk patients after hip surgery.

PubMed

Carson, Jeffrey L; Terrin, Michael L; Noveck, Helaine; Sanders, David W; Chaitman, Bernard R; Rhoads, George G; Nemo, George; Dragert, Karen; Beaupre, Lauren; Hildebrand, Kevin; Macaulay, William; Lewis, Courtland; Cook, Donald Richard; Dobbin, Gwendolyn; Zakriya, Khwaja J; Apple, Fred S; Horney, Rebecca A; Magaziner, Jay

2011-12-29

The hemoglobin threshold at which postoperative red-cell transfusion is warranted is controversial. We conducted a randomized trial to determine whether a higher threshold for blood transfusion would improve recovery in patients who had undergone surgery for hip fracture. We enrolled 2016 patients who were 50 years of age or older, who had either a history of or risk factors for cardiovascular disease, and whose hemoglobin level was below 10 g per deciliter after hip-fracture surgery. We randomly assigned patients to a liberal transfusion strategy (a hemoglobin threshold of 10 g per deciliter) or a restrictive transfusion strategy (symptoms of anemia or at physician discretion for a hemoglobin level of <8 g per deciliter). The primary outcome was death or an inability to walk across a room without human assistance on 60-day follow-up. A median of 2 units of red cells were transfused in the liberal-strategy group and none in the restrictive-strategy group. The rates of the primary outcome were 35.2% in the liberal-strategy group and 34.7% in the restrictive-strategy group (odds ratio in the liberal-strategy group, 1.01; 95% confidence interval [CI], 0.84 to 1.22), for an absolute risk difference of 0.5 percentage points (95% CI, -3.7 to 4.7). The rates of in-hospital acute coronary syndrome or death were 4.3% and 5.2%, respectively (absolute risk difference, -0.9%; 99% CI, -3.3 to 1.6), and rates of death on 60-day follow-up were 7.6% and 6.6%, respectively (absolute risk difference, 1.0%; 99% CI, -1.9 to 4.0). The rates of other complications were similar in the two groups. A liberal transfusion strategy, as compared with a restrictive strategy, did not reduce rates of death or inability to walk independently on 60-day follow-up or reduce in-hospital morbidity in elderly patients at high cardiovascular risk. (Funded by the National Heart, Lung, and Blood Institute; FOCUS ClinicalTrials.gov number, NCT00071032.).

Hemoglobin level as a risk factor for lower respiratory tract infections in Lebanese children.

PubMed

Mourad, Sawsan; Rajab, Mariam; Alameddine, Aouni; Fares, Mohammad; Ziade, Fouad; Merhi, Bassem Abou

2010-10-01

Pneumonia is the biggest single cause of childhood death under the age of 5 years, and anemia affects approximately 30% of infants and children all over the world. Determination of the relationship between anemia and lower respiratory tract infection as a risk factor in Lebanese children. A total number of two hundred infants and children aged nine months to twelve years were included; One hundred cases were hospitalized for lower respiratory tract infection in Department of Pediatrics, Makassed General Hospital, and one hundred healthy, age and sex matched controls, were selected from outpatient department. Complete blood count, iron level, ferritin level, and total iron binding capacity were taken if hemoglobin level less than eleven gram per deci-liter. In addition peripheral blood smear, chest radiograph and C-reactive protein were done to hospitalized cases. Definition of iron deficiency anemia and normal laboratory values were predetermined. Anemia was found in 32% of hospitalized cases and 16% of healthy controls. Mean hemoglobin level was 9.99 ± 0.62 gram per deci-liter and 11.99 ± 0.92 gram per deci-liter in anemic and non-anemic group respectively with a significant P-value of 0.001. C-reactive protein levels and number hospitalization days were similar among the anemic and non-anemic group. History of recurrent chest infections was significantly higher in both anemic group and hospitalized cases compared to non-anemic group and healthy controls. Low hemoglobin level was a risk factor for lower respiratory tract infection with a P-value of 0.008. Anemic children were two times more susceptible to lower respiratory tract infection compared to the control group, and iron deficiency anemia was predominating. Accurate diagnosis and prevention of anemia, whatever its etiology, is essential.

Identification of a Novel Class of Covalent Modifiers of Hemoglobin as Potential Antisickling Agents

PubMed Central

Omar, A. M.; Mahran, M. A.; Ghatge, M. S.; Chowdhury, N.; Bamane, F. H. A.; El-Araby, M. E.; Abdulmalik, O.; Safo, M. K.

2015-01-01

Aromatic aldehydes and ethacrynic acid (ECA) exhibit antipolymerization properties that are beneficial for sickle cell disease therapy. Based on ECA pharmacophore and its atomic interaction with hemoglobin, we designed and synthesized several compounds--designated as KAUS (imidazolylacryloyl derivatives)--that we hypothesized would bind covalently to βCys93 of hemoglobin and inhibit sickling. The compounds surprisingly showed weak allosteric and antisickling properties. X-ray studies of hemoglobin in complex with representative KAUS compounds revealed an unanticipated mode of Michael addition reaction between the β-unsaturated carbon and the N-terminal αVal1 nitrogen at the α-cleft of hemoglobin, with no observable interaction with βCys93. Interestingly, the compounds exhibited almost no reactivity with the free amino acids, L-Val, L-His and L-Lys, however showed some reactivity with both glutathione and L-Cys. Our findings provide a molecular level explanation to the compounds biological activities and an important framework for targeted modifications that would yield novel potent antisickling agents. PMID:25974708

The Influence of Glycated Hemoglobin on the Cross Susceptibility Between Type 1 Diabetes Mellitus and Periodontal Disease.

PubMed

Lappin, David F; Robertson, Douglas; Hodge, Penny; Treagus, David; Awang, Raja A; Ramage, Gordon; Nile, Christopher J

2015-11-01

Periodontal disease is a major complication of type 1 diabetes mellitus (T1DM). The aim of the present study is to investigate the relationship between glycated hemoglobin and circulating levels of interleukin (IL)-6, IL-8, and C-X-C motif chemokine ligand 5 (CXCL5) in non-smoking patients suffering from T1DM, with and without periodontitis. In addition, to determine the effect of advanced glycation end products (AGE) in the presence and absence of Porphyromonas gingivalis lipopolysaccharide (LPS) on IL-6, IL-8, and CXCL5 expression by THP-1 monocytes and OKF6/TERT-2 cells. There were 104 participants in the study: 19 healthy volunteers, 23 patients with periodontitis, 28 patients with T1DM, and 34 patients with T1DM and periodontitis. Levels of blood glucose/glycated hemoglobin (International Federation of Clinical Chemistry [IFCC]) were determined by high-performance liquid chromatography. Levels of IL-6, IL-8, and CXCL5 in plasma were determined by enzyme-linked immunosorbent assay (ELISA). In vitro stimulation of OKF6/TERT-2 cells and THP-1 monocytes was performed with combinations of AGE and P. gingivalis LPS. Changes in expression of IL-6, IL-8, and CXCL5 were monitored by ELISA and real-time polymerase chain reaction. Patients with diabetes and periodontitis had higher plasma levels of IL-8 than patients with periodontitis alone. Plasma levels of IL-8 correlated significantly with IFCC units, clinical probing depth, and attachment loss. AGE and LPS, alone or in combination, stimulated IL-6, IL-8, and CXCL5 expression in both OKF6/TERT-2 cells and THP-1 monocytes. Elevated plasma levels of IL-8 potentially contribute to the cross-susceptibility between periodontitis and T1DM. P. gingivalis LPS and AGE in combination caused significantly greater expression of IL-6, IL-8, and CXCL5 from THP-1 monocytes and OKF6/TERT-2 cells than LPS alone.

Prevalence of common hemoglobin variants in an afro-descendent Ecuadorian population

PubMed Central

2013-01-01

Background Hemoglobinopathies are among the most studied and frequent pathologies. These genetic disorders are considered a very important health care threat in many tropical countries. Ecuador is a tropical Latin-American country with an important presence of afro-descendants (7.2%). Afro-descendants are among the ethnic groups with higher frequency of hemoglobinopathies reported. Ambuqui is a region within the Imbabura province with an important presence of afro-descendants (>50%). The present study analyzed the frequency of the most common hemoglobin variants in an asymptomatic afro-descendent population using capillary electrophoresis. Findings From 114 individuals, 25 (22%) reported a hemoglobin variant. All individuals that presented hemoglobin variants were heterozygotes (asymptomatic). Hemoglobin S (sickle cell trait) was the most frequent variant found (14%), followed by hemoglobin E (4.4%), Fetal (2.6%) and C (1%). Conclusion Prevalence of hemoglobin S was consistent with populations from other countries, but it was lower than other Ecuadorian afro-descendent populations. Frequency of hemoglobin C was lower than other afro-descendent populations. This data suggests the possibility of gene flow from Native American individuals to the Ambuqui population there by lowering the frequency of their hemoglobin variants compared with other afro-descendant populations. Evaluating the frequency of hemoglobinopathies in Ecuadorian populations is essential. Despite the high frequency of these disorders, very few health care facilities implement hemoglobinopathies tests as a routine practice. PMID:23557107

Diagnostic approach to hemoglobins with high oxygen affinity: experience from France and Belgium and review of the literature.

PubMed

Orvain, Corentin; Joly, Philippe; Pissard, Serge; Badiou, Stéphanie; Badens, Catherine; Bonello-Palot, Nathalie; Couque, Nathalie; Gulbis, Béatrice; Aguilar-Martinez, Patricia

2017-02-01

Congenital causes of erythrocytosis are now more easily identified due to the improvement of the molecular characterization of many of them. Among these causes, hemoglobins with high oxygen affinity take a large place. The aim of this work was to reevaluate the diagnostic approach of these disorders. To assess the current practices, we sent a questionnaire to the expert laboratories in the diagnosis of hemoglobinopathies in France and Belgium. In parallel, we gathered the methods used for the diagnosis of the hemoglobins with high oxygen affinity indexed in the international database HbVar. Even though they remain a rare cause of erythrocytosis (1 to 5 positive diagnosis every year in each of the questioned specialized laboratories), hemoglobins with high oxygen affinity are increasingly suspected by clinicians. Phenotypic assessment by laboratory techniques remains a main step in their diagnosis as it enables the finding of 93% of them in the questioned laboratories (28 of the 30 variants diagnosed during the last 5 years). Among the 96 hemoglobin variants with high oxygen affinity indexed in the international database, 87% could be diagnosed with phenotypic techniques. A direct measure of the p50 with the Hemox-Analyzer is included in the diagnostic approach of half of the laboratories only, because of the poor availability of this apparatus. Comparatively, the estimation of p50 by blood gas analyzers on venous blood is a much more convenient and attractive method but due to the lack of proof as to its effectiveness in the diagnosis of hemoglobins with high oxygen affinity, it requires further investigations. Beta- and alphaglobin genes analysis by molecular biology techniques is essential as it either allows a quick and definite identification of the variant or definitely excludes the diagnosis. It is thus systematically performed as a first or second step method, according to the laboratory practice.

BCL11A Enhancer Haplotypes and Fetal Hemoglobin in Sickle Cell Anemia

PubMed Central

Sebastiani, P.; Farrell, J.J.; Alsultan, A.; Wang, S.; Edward, H. L.; Shappell, H.; Bae, H.; Milton, J. N.; Baldwin, C.T.; Al-Rubaish, A.M.; Naserullah, Z.; Al-Muhanna, F.; Alsuliman, A.; Patra, P. K.; Farrer, L.A.; Ngo, D.; Vathipadiekal, V.; Chui, D.H.K.; Al-Ali, A.K.; Steinberg, M.H.

2015-01-01

Background Fetal hemoglobin (HbF) levels in sickle cell anemia patients vary. We genotyped polymorphisms in the erythroid-specific enhancer of BCL11A to see if they might account for the very high HbF associated with the Arab-Indian (AI) haplotype and Benin haplotype of sickle cell anemia. Methods and Results Six BCL112A enhancer SNPs and their haplotypes were studied in Saudi Arabs from the Eastern Province and Indian patients with AI haplotype (HbF ~20%), African Americans (HbF ~7%), and Saudi Arabs from the Southwestern Province (HbF ~12%). Four SNPs (rs1427407, rs6706648, rs6738440, and rs7606173) and their haplotypes were consistently associated with HbF levels. The distributions of haplotypes differ in the 3 cohorts but not their genetic effects: the haplotype TCAG was associated with the lowest HbF level and the haplotype GTAC was associated with the highest HbF level and differences in HbF levels between carriers of these haplotypes in all cohorts was approximately 6%. Conclusions Common HbF BCL11A enhancer haplotypes in patients with African origin and AI sickle cell anemia have similar effects on HbF but they do not explain their differences in HbF. PMID:25703683

Environmental lead exposure among primary school children in Shebin El-Kom District, Menoufiya Governorate, Egypt.

PubMed

Abdel Rasoul, G M; Al-Batanony, M A; Mahrous, O A; Abo-Salem, M E; Gabr, H M

2012-10-01

Lead still remains an important problem for poor, inner-city, ethnic minority children, with a particular emphasis on lead paint and dust. In Egypt, there is no national survey about the prevalence of elevated blood lead level among children. To assess the environmental lead level as well as to determine blood lead level among primary school children and find out its relationship with their intelligent quotient (IQ), hemoglobin level, hearing impairment and school performance. 190 primary school children from rural and urban areas were selected and their blood lead levels (BLL), hemoglobin concentrations, IQ, hearing threshold and school performance were measured. Also, environmental lead level was measured in the school and home. The mean value of environmental lead (μg/m3) in urban schools air was significantly higher than that in rural areas. BLL had a significant negative correlation with hemoglobin level and IQ; it was positively correlated with the hearing threshold. With increasing BLL, the school performance of children decreased significantly. Exposure to lead would deteriorate IQ, school performance and hearing level of school children. Even in the absence of overt clinical manifestations of lead toxicity, lead intoxication should be among differential diagnosis in children presenting anemia, intellectual impairment, poor academic performance and hearing impairment.

[EFFICIENCY OF HAEMOGLOBIN REGENERATION IN THE NUTRITIONAL FERROPENIC ANAEMIA RECOVERY WITH GOAT MILK-BASED DIETS].

PubMed

Serrano Reina, José Antonio; Nestares Pleguezuelo, Teresa; Muñoz Alférez, Ma José; Díaz Castro, Javier; López Aliaga, Ma Inmaculada

2015-10-01

in spite of the high incidence/prevalence of iron deficiency anemia (IDA) and the beneficial effects derived from the consumption of goat milk, scarce is known about the recovery of the anemia following a balanced diet accompanied by the intake of goat milk of goat. The aim of the current study is to assess, in rats with experimentally induced nutritional iron deficiency anemia, the effects of goat or cow milk-based diets, supplied during 30 days, on the recovery of the anemia and the efficiency of regeneration of the hemoglobin. 40 male Wistar albino rats newly weaned were divided at random in two experimental groups and they were fed ad libitum for 40 days with AIN-93G diet, either with normal iron content (control group, 45 mg/kg diet), or low iron content (anaemic group, 5 mg/kg diet). Samples of blood form the caudal vein were collected for the hematologic control of the anemia. Later, both experimental groups (control and iron deficient) were fed for 30 days with goat or cow milk- based diets. After finishing the experimental period and previous anesthesia the animals were withdrawn by canulation of the abdominal aorta, and the obtained blood was gathered in tubes with EDTA as anticoagulant for the later determination of hematologic parameters and the efficiency of regeneration of the hemoglobin. after the consumption of a diet with low iron content during 40 days, the rats were anaemic, with a concentration of hemoglobin, hematocrit, serum iron, mean corpuscular volume (MCV), serum ferritin and low transferrin (p < 0.001), whereas the levels of platelets and the total iron binding capacity (TIBC) were raised (p < 0.001), findings consistent with the anemia induced experimentally in the animals. The efficiency of regeneration of the hemoglobin was higher in control and anaemic rats fed goat milk-based diet in comparison with those fed cow milk-based diet (p < 0.001) due to, partly, to the major levels of serum iron and hemoglobin, and to the best nutritive utilization of iron in the animals that consumed the goat milk-based diet thanks to the excellent nutritional characteristics of this type of milk. the consumption during 30 days of goat or cow milk-based diets favors the recovery of the iron deficiency anemia, especially with the goat milk, due to the major efficiency of regeneration of the hemoglobin, index that shows the quantity of iron of the diet used for the synthesis of hemoglobin. Therefore, it would be recommendable the consumption of goat milk in the context of a balanced diet in healthy populations and, especially in those at risk of suffering iron deficiency. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

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

NASA Astrophysics Data System (ADS)

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

2014-03-01

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

Hemoglobin magnetism in aqueous solution probed by muon spin relaxation and future applications to brain research

PubMed Central

Nagamine, Kanetada; Shimomura, Koichiro; Miyadera, Haruo; Kim, Yong-Jae; Scheicher, Ralph Hendrik; Das, Tara Prasad; Schultz, Jerome Samson

2007-01-01

A marked difference in spin relaxation behavior due to hemoglobin magnetism was found for positive muons (μ+) in deoxyhemoglobin in comparison with that observed in oxyhemoglobin in aqueous solution at room temperature under zero and external longitudinal magnetic fields upto 0.4 Tesla. At the same time, small but significant unique relaxation pattern was observed in nonmagnetic oxyhemoglobin. Combined with our previous measurements on hemoglobin in human blood, application of this type of measurement to the studies of the level of oxygenation in various regions of the human brain is suggested. PMID:24019590

Do high blood folate concentrations exacerbate metabolic abnormalities in people with low vitamin B-12 status?123

PubMed Central

Mills, James L; Carter, Tonia C; Scott, John M; Troendle, James F; Gibney, Eileen R; Shane, Barry; Kirke, Peadar N; Ueland, Per M; Brody, Lawrence C; Molloy, Anne M

2011-01-01

Background: In elderly individuals with low serum vitamin B-12, those who have high serum folate have been reported to have greater abnormalities in the following biomarkers for vitamin B-12 deficiency: low hemoglobin and elevated total homocysteine (tHcy) and methylmalonic acid (MMA). This suggests that folate exacerbates vitamin B-12–related metabolic abnormalities. Objective: We determined whether high serum folate in individuals with low serum vitamin B-12 increases the deleterious effects of low vitamin B-12 on biomarkers of vitamin B-12 cellular function. Design: In this cross-sectional study, 2507 university students provided data on medical history and exposure to folic acid and vitamin B-12 supplements. Blood was collected to measure serum and red blood cell folate (RCF), hemoglobin, plasma tHcy, and MMA, holotranscobalamin, and ferritin in serum. Results: In subjects with low vitamin B-12 concentrations (<148 pmol/L), those who had high folate concentrations (>30 nmol/L; group 1) did not show greater abnormalities in vitamin B-12 cellular function in any area than did those with lower folate concentrations (≤30 nmol/L; group 2). Group 1 had significantly higher holotranscobalamin and RCF, significantly lower tHcy, and nonsignificantly lower (P = 0.057) MMA concentrations than did group 2. The groups did not differ significantly in hemoglobin or ferritin. Compared with group 2, group 1 had significantly higher mean intakes of folic acid and vitamin B-12 from supplements and fortified food. Conclusions: In this young adult population, high folate concentrations did not exacerbate the biochemical abnormalities related to vitamin B-12 deficiency. These results provide reassurance that folic acid in fortified foods and supplements does not interfere with vitamin B-12 metabolism at the cellular level in a healthy population. PMID:21653798

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

PubMed

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 (<5.7%), Middle group (5.7-6.0%), and 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.

Pulsed high oxygen induces a hypoxic-like response in human umbilical endothelial cells and in humans.

PubMed

Cimino, F; Balestra, C; Germonpré, P; De Bels, D; Tillmans, F; Saija, A; Speciale, A; Virgili, F

2012-12-01

It has been proposed that relative changes of oxygen availability, rather than steady-state hypoxic or hyperoxic conditions, play an important role in hypoxia-inducible factor (HIF) transcriptional effects. According to this hypothesis describing the "normobaric oxygen paradox", normoxia following a hyperoxic event is sensed by tissues as an oxygen shortage, upregulating HIF-1 activity. With the aim of confirming, at cellular and at functional level, that normoxia following a hyperoxic event is "interpreted" as a hypoxic event, we report a combination of experiments addressing the effects of an intermittent increase of oxygen concentration on HIF-1 levels and the activity level of specific oxygen-modulated proteins in cultured human umbilical vein endothelial cells and the effects of hemoglobin levels after intermittent breathing of normobaric high (100%) and low (15%) oxygen in vivo in humans. Our experiments confirm that, during recovery after hyperoxia, an increase of HIF expression occurs in human umbilical vein endothelial cells, associated with an increase of matrix metalloproteinases activity. These data suggest that endothelial cells "interpret" the return to normoxia after hyperoxia as a hypoxic stimulus. At functional level, our data show that breathing both 15 and 100% oxygen 30 min every other day for a period of 10 days induces an increase of hemoglobin levels in humans. This effect was enhanced after the cessation of the oxygen breathing. These results indicate that a sudden decrease in tissue oxygen tension after hyperoxia may act as a trigger for erythropoietin synthesis, thus corroborating the hypothesis that "relative" hypoxia is a potent stimulator of HIF-mediated gene expressions.

Presence of metabolic syndrome in football linemen.

PubMed

Buell, Jackie L; Calland, Doug; Hanks, Fiona; Johnston, Bruce; Pester, Benjamin; Sweeney, Robert; Thorne, Robert

2008-01-01

Metabolic syndrome is a clustering of symptoms associated with abdominal obesity that demonstrates a high risk for cardiovascular disease and type II diabetes mellitus. To evaluate football linemen in National Collegiate Athletic Association Divisions I, II, and III schools for the presence of metabolic syndrome according to the American Heart Association/National Heart, Lung, and Blood Institute criteria as well as to document other related biomarkers. Cross-sectional descriptive study. Three university locations on the first full day of football camp in early morning. Of 76 football linemen, 70 were able to provide blood samples. Height, mass, blood pressure, upper-body skinfolds, and waist circumference were measured at various stations. Two small venous samples of blood were collected and analyzed in a hospital laboratory for fasting insulin, glucose, high-density lipoprotein, total cholesterol, triglycerides, C-reactive protein, and glycosylated hemoglobin. The last station was a verbal family history for cardiovascular disease and diabetes; also, athletes filled out a nutrition attitudes questionnaire. Of the 70 athletes, 34 were identified as having metabolic syndrome according to measures of blood pressure, waist circumference, fasting glucose, high-density lipoprotein, and triglycerides. The mean total cholesterol-to-high-density lipoprotein cholesterol ratio for the group was 4.95, with 32 participants displaying values higher than 5.0. Twelve volunteers had total cholesterol levels greater than 200 mmol/L, 15 had high levels of C-reactive protein, and 9 had slightly elevated levels of glycosylated hemoglobin. Although athletes might be assumed to be protected from risks of cardiovascular disease, we found a high incidence of metabolic syndrome and other associated adverse biomarkers for heart disease in collegiate football linemen. Early screening, awareness, and intervention may have favorable effects on the overall health outcomes of football linemen.

Comparison of intravenous versus topical tranexamic acid in total knee arthroplasty: a prospective randomized study.

PubMed

Patel, Jay N; Spanyer, Jonathon M; Smith, Langan S; Huang, Jiapeng; Yakkanti, Madhusudhan R; Malkani, Arthur L

2014-08-01

The purpose of this study was to compare the efficacy of topical Tranexamic Acid (TXA) versus Intravenous (IV) Tranexamic Acid for reduction of blood loss following primary total knee arthroplasty (TKA). This prospective randomized study involved 89 patients comparing topical administration of 2.0g TXA, versus IV administration of 10mg/kg. There were no differences between the two groups with regard to patient demographics or perioperative function. The primary outcome measure, perioperative change in hemoglobin level, showed a decrease of 3.06 ± 1.02 in the IV group and 3.42 ± 1.07 in the topical group (P = 0.108). There were no statistical differences between the groups in preoperative hemoglobin level, lowest postoperative hemoglobin level, or total drain output. One patient in the topical group required blood transfusion (P = 0.342). Based on our study, topical Tranexamic Acid has similar efficacy to IV Tranexamic Acid for TKA patients. Copyright © 2014 Elsevier Inc. All rights reserved.

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

PubMed

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.

Characteristics of High-Resolution Hemoglobin Measurement Microchip Integrated with Signal Processing Circuit

NASA Astrophysics Data System (ADS)

Noda, Toshihiko; Takao, Hidekuni; Ashiki, Mitsuaki; Ebi, Hiroyuki; Sawada, Kazuaki; Ishida, Makoto

2004-04-01

In this study, a microchip for measurement of hemoglobin in human blood has been proposed, fabricated and evaluated. The measurement principle of hemoglobin is based on the “cyanmethemoglobin method” that calculates the cyanmethemoglobin concentration by absorption photometry. A glass/silicon/silicon structure was used for the microchip. The middle silicon layer includes flow channels, and 45° mirrors formed at each end of the flow channels. Photodiodes and metal oxide semiconductor (MOS) integrated circuits were fabricated on the bottom silicon layer. The performance of the microchip for hemoglobin measurement was evaluated using a solution of red food color instead of a real blood sample. The fabricated microchip exhibited a similar performance to a nonminiaturized absorption cell which has the same optical path length. Signal processing output varied with solution concentration from 5.32 V to 5.55 V with very high stability due to differential signal processing.

Hemoglobin Decline in Children with Chronic Kidney Disease: Baseline Results from the Chronic Kidney Disease in Children Prospective Cohort Study

PubMed Central

Fadrowski, Jeffrey J.; Pierce, Christopher B.; Cole, Stephen R.; Moxey-Mims, Marva; Warady, Bradley A.; Furth, Susan L.

2008-01-01

Background and objectives: The level of glomerular filtration rate at which hemoglobin declines in chronic kidney disease is poorly described in the pediatric population. Design, setting, participants, & measurements: This cross-sectional study of North American children with chronic kidney disease examined the association of glomerular filtration rate, determined by the plasma disappearance of iohexol, and hemoglobin concentration. Results: Of the 340 patients studied, the mean age was 11 ± 4 yr, the mean glomerular filtration rate was 42 ± 14 ml/min per 1.73 m2, and the mean hemoglobin was 12.5 ± 1.5. Below a glomerular filtration rate of 43, the hemoglobin declined by 0.3 g/dl (95% confidence interval −0.2 to −0.5) for every 5-ml/min per 1.73 m2 decrease in glomerular filtration rate. Above a glomerular filtration rate of 43 ml/min per 1.73 m2, the hemoglobin showed a nonsignificant decline of 0.1 g/dl for every 5-ml/min per 1.73 m2 decrease in glomerular filtration rate. Conclusions: In pediatric patients with chronic kidney disease, hemoglobin declines as an iohexol-determined glomerular filtration rate decreases below 43 ml/min per 1.73 m2. Because serum creatinine–based estimated glomerular filtration rates may overestimate measured glomerular filtration rate in this population, clinicians need to be mindful of the potential for hemoglobin decline and anemia even at early stages of chronic kidney disease, as determined by current Schwartz formula estimates. Future longitudinal analyses will further characterize the relationship between glomerular filtration rate and hemoglobin, including elucidation of reasons for the heterogeneity of this association among individuals. PMID:18235140

Impact of race/ethnicity on the efficacy and safety of commonly used insulin regimens: a post hoc analysis of clinical trials in type 2 diabetes mellitus.

PubMed

Davidson, Jaime A; Lacaya, Lyndon B; Jiang, Honghua; Heilmann, Cory R; Scism-Bacon, Jamie L; Gates, Jeffrey R; Jackson, Jeffrey A

2010-01-01

To explore the impact of race/ethnicity on the efficacy and safety of commonly used insulin regimens in patients with type 2 diabetes mellitus. In this post hoc analysis, pooled data from 11 multinational clinical trials involving 1455 patients with type 2 diabetes were used to compare specific insulin treatments in Latino/Hispanic, Asian, African-descent, and Caucasian patients. Insulin treatments included once daily insulin glargine or neutral protamine Hagedorn (BASAL), insulin lispro mix 75/25 twice daily (LMBID), or insulin lispro mix 50/50 three times daily (LMTID). Race/ethnicity was associated with significant outcome differences for each of the insulin regimens. BASAL therapy was associated with greater improvement in several measures of glycemic control among Latino/Hispanic patients compared with Caucasian patients (lower end point hemoglobin A1c, greater reduction in hemoglobin A1c from baseline, and a larger proportion of patients achieving hemoglobin A1c level <7%). In contrast, LMBID therapy was associated with higher end point hemoglobin A1c and a smaller decrease in hemoglobin A1c from baseline in Latino/Hispanic and Asian patients than in Caucasian patients. Furthermore, fewer Asian patients attained a hemoglobin A1c level <7% than did Caucasians patients. For LMTID therapy, hemoglobin A1c outcomes were comparable across patient groups. Fasting blood glucose and glycemic excursions varied among racial/ethnic groups for the 3 insulin regimens. Weight change was comparable among racial/ethnic groups in each insulin regimen. During treatment with LMTID, Asian patients experienced higher incidence and rate of severe hypoglycemia than Caucasian patients. Latino/Hispanic, Asian, and African-descent patients with type 2 diabetes show different metabolic responses to insulin therapy, dependent in part on insulin type and regimen intensity.

B-type natriuretic peptide and plasma hemoglobin levels following transfusion of shorter-storage versus longer-storage Red Blood Cells: results from the TOTAL randomized trial

PubMed Central

Dhabangi, Aggrey; Ainomugisha, Brenda; Cserti-Gazdewich, Christine; Ddungu, Henry; Kyeyune, Dorothy; Musisi, Ezra; Opoka, Robert; Stowell, Christopher P.; Dzik, Walter H

2016-01-01

Background Prior studies have suggested that transfusion of stored RBCs with increased levels of cell free hemoglobin might reduce the bioavailability of recipient nitric oxide (NO) and cause myocardial strain. Methods Ugandan children (ages 6 to 60 months) with severe anemia and lactic acidosis were randomly assigned to receive RBCs stored 1-10 days versus 25-35 days. B-type natriuretic peptide (BNP), vital signs, renal function tests, and plasma hemoglobin were measured. Most children had either malaria or sickle cell disease and were thus at risk for reduced NO bioavailability. Results 70 patients received RBCs stored 1-10 days and 77 received RBCs stored 25-35 days. The median (IQR) cell free hemoglobin was nearly three times higher in longer-storage RBCs (26.4 [15.5-43.4] μmol/L) than in shorter-storage RBCs (10.8 [7.8-18.6] μmol/L), p<0.0001. Median (IQR) BNP 2 hours post-transfusion was 156 (59-650) pg/mL (shorter-storage) versus 158 (59-425) pg/mL (longer-storage), p=0.76. BNP values 22 hours post-transfusion were 110 (46-337) pg/mL (shorter-storage) versus 96 (49-310) pg/mL (longer-storage), p=0.76. Changes in BNP within individuals from pre-transfusion to 2-hour (or 22-hour) post-transfusion were not significantly different between the study groups. BNP change following transfusion did not correlate with the concentration of cell free hemoglobin in the RBC supernatant. Blood pressure, BUN, creatinine, and change in plasma hemoglobin were not significantly different in the two groups. Conclusion In a randomized trial among children at risk for reduced NO bioavailability, we found that BNP, blood pressure, creatinine, and plasma hemoglobin were not higher in patients receiving RBCs stored for 25-35 days versus 1-10 days. PMID:27302626

Diet and iron status of nonpregnant women in rural Central Mexico.

PubMed

Backstrand, Jeffrey R; Allen, Lindsay H; Black, Anne K; de Mata, Margarita; Pelto, Gretel H

2002-07-01

Few studies have examined the relation of iron status to diet in populations from developing countries with high levels of iron deficiency and diets of poor quality. The objective was to identify nutrients, dietary constituents, and foods that are associated with better iron status in a rural Mexican population. A prospective cohort study was conducted in rural central Mexico. The subjects were 125 nonpregnant women aged 16-44 y. During the 12 mo before blood collection, food intakes were assessed repeatedly by a combination of dietary recalls, food weighing, and food diaries [mean (+/-SD) days of food intake data: 18.8 +/- 5.9 d]. Hemoglobin, hematocrit, and plasma ferritin were measured at the end of the study. Higher plasma ferritin concentrations were associated with greater intakes of nonheme iron and ascorbic acid after control for age, BMI, breast-feeding, season, and the time since the birth of the last child. Higher ascorbic acid intakes, but not higher intakes of heme and nonheme iron, predicted a lower risk of low hemoglobin and hematocrit values after control for the background variables. Consumption of the alcoholic beverage pulque predicted a lower risk of low ferritin and low hemoglobin values. Seasonal variation in ferritin, hemoglobin, and hematocrit values was observed. Better iron status was associated with greater intakes of foods containing nonheme iron and ascorbic acid. PULQUE:a beverage containing iron, ascorbic acid, and alcohol-may influence the iron status of women in rural central Mexico.

Laboratory evaluations of erectile dysfunction: an evidence based approach.

PubMed

Bodie, Joshua; Lewis, Jean; Schow, Doug; Monga, Manoj

2003-06-01

We evaluate the prevalence of laboratory abnormalities in men presenting for initial evaluation and therapy of erectile dysfunction. The computerized charts of men receiving treatment for erectile dysfunction from 1987 to 2002 were retrospectively reviewed. We pooled laboratory data for 3,547 men with erectile dysfunction to assess the prevalence of laboratory abnormalities. Values of the common laboratory screening tests for erectile dysfunction were recorded for testosterone, prolactin, luteinizing hormone, thyroid-stimulating hormone, hemoglobin A(Ic), prostate specific antigen, hemoglobin, cholesterol and creatinine. Of those patients evaluated 18.7% had low testosterone, 4.6% had increased prolactin, 14.6% had abnormal luteinizing hormone, 4.0% had increased thyroid-stimulating hormone, 8.3% had increased prostate specific antigen, 26.5% had anemia and 11.9% tested had renal insufficiency. A high percentage of patients presenting with a primary complaint of erectile dysfunction had increased hemoglobin A(Ic) and total serum cholesterol levels (52.9% and 48.4%, respectively). An evidence based approach to standardization of laboratory evaluations for men presenting with erectile dysfunction is recommended. Laboratory screening should be directed to identify those risk factors that may benefit from lifestyle modification and pharmacological intervention.

Point-of-care hemoglobin testing for postmortem diagnosis of anemia.

PubMed

Na, Joo-Young; Park, Ji Hye; Choi, Byung Ha; Kim, Hyung-Seok; Park, Jong-Tae

2018-03-01

An autopsy involves examination of a body using invasive methods such as dissection, and includes various tests using samples procured during dissection. During medicolegal autopsies, the blood carboxyhemoglobin concentration is commonly measured using the AVOXimeter® 4000 as a point-of-care test. When evaluating the body following hypovolemic shock, characteristics such as reduced livor mortis or an anemic appearance of the viscera can be identified, but these observations arequite subjective. Thus, a more objective test is required for the postmortem diagnosis of anemia. In the present study, the AVOXimeter® 4000 was used to investigate the utility of point-of-care hemoglobin testing. Hemoglobin tests were performed in 93 autopsy cases. The AVOXimeter® 4000 and the BC-2800 Auto Hematology Analyzer were used to test identical samples in 29 of these cases. The results of hemoglobin tests performed with these two devices were statistically similar (r = 0.969). The results of hemoglobin tests using postmortem blood were compared with antemortem test results from medical records from 31 cases, and these results were similar. In 13 of 17 cases of death from internal hemorrhage, hemoglobin levels were lower in the cardiac blood than in blood from the affected body cavity, likely due to compensatory changes induced by antemortem hemorrhage. It is concluded that blood hemoglobin testing may be useful as a point-of-care test for diagnosing postmortem anemia.

Gel Filtration Of Dilute Human Embryonic Hemoglobins Reveals Basis For Their Increased Oxygen Binding

PubMed Central

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

2016-01-01

This report establishes a correlation between two known properties of the human embryonic hemoglobins-- their weak subunit assemblies as demonstrated here by gel filtration at very dilute protein concentrations and their high oxygen affinities and reduced cooperativities reported previously by others but without a mechanistic basis. We demonstrate here that their high oxygen affinities are a consequence of their weak assemblies. Weak vs strong hemoglobin tetramers represent a regulatory mechanism to modulate oxygen binding capacity by altering the equilibrium between the various steps in the assembly process that can be described as an inverse allosteric effect. PMID:27965062

Gel filtration of dilute human embryonic hemoglobins reveals basis for their increased oxygen binding.

PubMed

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

2017-02-15

This report establishes a correlation between two known properties of the human embryonic hemoglobins-- their weak subunit assemblies as demonstrated here by gel filtration at very dilute protein concentrations and their high oxygen affinities and reduced cooperativities reported previously by others but without a mechanistic basis. We demonstrate here that their high oxygen affinities are a consequence of their weak assemblies. Weak vs strong hemoglobin tetramers represent a regulatory mechanism to modulate oxygen binding capacity by altering the equilibrium between the various steps in the assembly process that can be described as an inverse allosteric effect. Copyright © 2016 Elsevier Inc. All rights reserved.

Effect of potentially interfering substances on the measurement of HIV-1 viral load by the bDNA assay.

PubMed

Alonso, R; García de Viedma, D; Rodríguez-Creixems, M; Bouza, E

1999-03-01

As high heterogeneity of plasma composition may be responsible for interference with HIV-1 viral load determination by the bDNA assay, the potential interference caused by a number of plasma components was examined. Among the biochemical substances assayed, cholesterol, bilirubin, and triglycerides did not affect viral load quantification. Hemoglobin did not interfere with the assay at concentrations lower than or equal to 14 g/dl. Above this concentration, measurements decreased by up to 0.78 log, but these hemoglobin levels do not usually occur in the clinical setting. None of the antiretroviral drugs assayed (AZT, dDC, d4T, 3TC and Indinavir) interfered with the measurement. HIV bDNA is a robust assay even in those frequent circumstances in which plasma composition differs notably from normal.

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

PubMed

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

2017-08-01

In this study we identify and classify high and low levels of glycated hemoglobin (HbA1c) in healthy volunteers (HV) and diabetic patients (DP). Overall, 86 subjects were evaluated. The Raman spectrum was measured in three anatomical regions of the body: index fingertip, right ear lobe, and forehead. The measurements were performed to compare the difference between the HV and DP (22 well controlled diabetic patients (WCDP) (HbA1c <6.5%), and 49 not controlled diabetic patients (NCDP) (HbA1c ≥6.5%)). Multivariable methods such as principal components analysis (PCA) combined with support vector machine (SVM) were used to develop effective diagnostic algorithms for classification among these groups. The forehead of HV versus WCDP showed the highest sensitivity (100%) and specificity (100%). Sensitivity (100%) and specificity (60%), were highest in the forehead of WCDP, versus NCDP. In HV versus NCDP, the fingertip had the highest sensitivity (100%) and specificity (80%). The efficacy of the diagnostic algorithm by receiver operating characteristic (ROC) curve was confirmed. Overall, our study demonstrated that the combination of Raman spectroscopy and PCA-SVM are feasible non-invasive diagnostic tool in diabetes to classify qualitatively high and low levels of HbA1c in vivo. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Low Hemoglobin among Pregnant Women in Midwives Practice of Primary Health Care, Jatinangor, Indonesia: Iron Deficiency Anemia or β-Thalassemia Trait?

PubMed Central

Susanti, Ari Indra; Winarno, Gatot; Sugianli, Adhi Kristianto; Susanto, Herman; Panigoro, Ramdan

2017-01-01

Low hemoglobin (Hb) or anemia is common among pregnant women in developing countries which may cause adverse pregnancy outcomes and maternal deaths. Our study aimed to assess Hb level measured by midwives in primary health care facility at rural area of Jatinangor, Indonesia, and to explore whether the anemia was due to iron deficiency (IDA) or β-thalassemia trait (β-TT). Pregnant women (n = 105) had finger prick test for Hb level during a regular antenatal care examination from October to November 2016. Hb level by finger prick test was compared with venous blood, measured by complete blood count (CBC). Indices including MCV and MCH and indices of Shine & Lal, Mentzer, Srivastava, Engels & Frase, Ehsani, and Sirdah were analyzed to differentiate anemia due to IDA and anemia due to suspect β-TT. HbA2 was measured to confirm β-TT. Anemic pregnant women were found in 86.7% by finger prick test compared to 21.9% (n = 23) by CBC. The prevalence of β-TT in our study was 5.7%. Hb measurement among pregnant women in low resource area is highly important; however, finger prick test in this study showed a high frequency of anemia which may lead to iron oversupplementation. A standard CBC is encouraged; MCV and MCH would help midwives to identify β-TT. PMID:28634546

High Presence of Extracellular Hemoglobin in the Periventricular White Matter Following Preterm Intraventricular Hemorrhage

PubMed Central

Ley, David; Romantsik, Olga; Vallius, Suvi; Sveinsdóttir, Kristbjörg; Sveinsdóttir, Snjolaug; Agyemang, Alex A.; Baumgarten, Maria; Mörgelin, Matthias; Lutay, Nataliya; Bruschettini, Matteo; Holmqvist, Bo; Gram, Magnus

2016-01-01

Severe cerebral intraventricular hemorrhage (IVH) in preterm infants continues to be a major clinical problem, occurring in about 15–20% of very preterm infants. In contrast to other brain lesions the incidence of IVH has not been reduced over the last decade, but actually slightly increased. Currently over 50% of surviving infants develop post-hemorrhagic ventricular dilatation and about 35% develop severe neurological impairment, mainly cerebral palsy and intellectual disability. To date there is no therapy available to prevent infants from developing either hydrocephalus or serious neurological disability. It is known that blood rapidly accumulates within the ventricles following IVH and this leads to disruption of normal anatomy and increased local pressure. However, the molecular mechanisms causing brain injury following IVH are incompletely understood. We propose that extracellular hemoglobin is central in the pathophysiology of periventricular white matter damage following IVH. Using a preterm rabbit pup model of IVH the distribution of extracellular hemoglobin was characterized at 72 h following hemorrhage. Evaluation of histology, histochemistry, hemoglobin immunolabeling and scanning electron microscopy revealed presence of extensive amounts of extracellular hemoglobin, i.e., not retained within erythrocytes, in the periventricular white matter, widely distributed throughout the brain. Furthermore, double immunolabeling together with the migration and differentiation markers polysialic acid neural cell adhesion molecule (PSA-NCAM) demonstrates that a significant proportion of the extracellular hemoglobin is distributed in areas of the periventricular white matter with high extracellular plasticity. In conclusion, these findings support that extracellular hemoglobin may contribute to the pathophysiological processes that cause irreversible damage to the immature brain following IVH. PMID:27536248

Correction of Murine Sickle Cell Disease Using γ-Globin Lentiviral Vectors to Mediate High-level Expression of Fetal Hemoglobin

PubMed Central

Pestina, Tamara I; Hargrove, Phillip W; Jay, Dennis; Gray, John T; Boyd, Kelli M; Persons, Derek A

2008-01-01

Increased levels of red cell fetal hemogloblin, whether due to hereditary persistence of expression or from induction with hydroxyurea therapy, effectively ameliorate sickle cell disease (SCD). Therefore, we developed erythroid-specific, γ-globin lentiviral vectors for hematopoietic stem cell (HSC)-targeted gene therapy with the goal of permanently increasing fetal hemoglobin (HbF) production in sickle red cells. We evaluated two different γ-globin lentiviral vectors for therapeutic efficacy in the BERK sickle cell mouse model. The first vector, V5, contained the γ-globin gene driven by 3.1 kb of β-globin regulatory sequences and a 130-bp β-globin promoter. The second vector, V5m3, was identical except that the γ-globin 3′-untranslated region (3′-UTR) was replaced with the β-globin 3′-UTR. Adult erythroid cells have β-globin mRNA 3′-UTR-binding proteins that enhance β-globin mRNA stability and we postulated this design might enhance γ-globin expression. Stem cell gene transfer was efficient and nearly all red cells in transplanted mice expressed human γ-globin. Both vectors demonstrated efficacy in disease correction, with the V5m3 vector producing a higher level of γ-globin mRNA which was associated with high-level correction of anemia and secondary organ pathology. These data support the rationale for a gene therapy approach to SCD by permanently enhancing HbF using a γ-globin lentiviral vector. PMID:19050697

Testosterone Administration Inhibits Hepcidin Transcription and is Associated with Increased Iron Incorporation into Red Blood Cells

PubMed Central

Guo, Wen; Bachman, Eric; Li, Michelle; Roy, Cindy N.; Blusztajn, Jerzy; Wong, Siu; Chan, Stephen Y.; Serra, Carlo; Jasuja, Ravi; Travison, Thomas G.; Muckenthaler, Martina U.; Nemeth, Elizabeta; Bhasin, Shalender

2013-01-01

Testosterone administration increases hemoglobin levels and has been used to treat anemia of chronic disease. Erythrocytosis is the most frequent adverse event associated with testosterone therapy of hypogonadal men, especially older men. However, the mechanisms by which testosterone increases hemoglobin remain unknown. Testosterone administration in male and female mice was associated with a greater increase in hemoglobin and hematocrit, reticulocyte count, reticulocyte hemoglobin concentration, and serum iron and transferring saturation than placebo. Testosterone downregulated hepatic hepcidin mRNA expression, upregulated renal erythropoietin mRNA expression, and increased erythropoietin levels. Testosterone-induced suppression of hepcidin expression was independent of its effects on erythropoietin or hypoxia-sensing mechanisms. Transgenic mice with liver-specific constitutive hepcidin over-expression failed to exhibit the expected increase in hemoglobin in response to testosterone administration. Testosterone upregulated splenic ferroportin expression and reduced iron retention in spleen. After intravenous administration of transferrin-bound 58Fe, the amount of 58Fe incorporated into red blood cells was significantly greater in testosterone-treated mice than in placebo-treated mice. Serum from testosterone-treated mice stimulated hemoglobin synthesis in K562 erythroleukemia cells more than that from vehicle-treated mice. Testosterone administration promoted the association of androgen receptor (AR) with Smad1 and Smad4 to reduce their binding to BMP-response elements in hepcidin promoter in the liver. Ectopic expression of AR in hepatocytes suppressed hepcidin transcription; this effect was blocked dose-dependently by AR antagonist flutamide. Testosterone did not affect hepcidin mRNA stability. Conclusion: Testosterone inhibits hepcidin transcription through its interaction with BMP-Smad signaling. Testosterone administration is associated with increased iron incorporation into red blood cells. PMID:23399021

Association between anemia and subclinical infection in children in Paraíba State, Brazil

PubMed Central

Sales, Márcia Cristina; de Queiroz, Everton Oliveira; Paiva, Adriana de Azevedo

2011-01-01

Background With subclinical infection, serum iron concentrations are reduced, altering the synthesis of hemoglobin, the main indicator of anemia. Objective To evaluate the association between subclinical infection and anemia in children of Paraíba State. Methods This is a cross-sectional study involving 1116 children aged 6 to 59 months from nine municipalities of Paraíba State. Demographic and socioeconomic data were collected by means of a specific questionnaire. The C-reactive protein and hemoglobin levels were determined by the latex agglutination technique and automated counter, respectively. C-reactive protein values ≥ 6 mg/L were used as indicative of subclinical infection, while the presence of anemia was determined by hemoglobin values < 11.0 g/dL. The data were analyzed using the Epi Info computer program, with significance being set at 5%. Results Data from this research showed that 80.1% of the children belonged to families that were below the bread line, with per capita income < ½ of the minimum wage at that time (R$ 350.00 approximately US$ 175.00). The prevalences of subclinical infection and anemia were 11.3% and 36.3%, respectively. Subclinical infection was significantly associated with anemia (p-value < 0.05). There were lower levels of hemoglobin in children with C-reactive protein ≥ 6 mg/L, with a mean hemoglobin level in children with subclinical infection of 10.93 g/dL (standard deviation - SD = 1.21 g/dL) and without infection of 11.26 g/dL (SD = 1.18 g/dL) (p-value < 0.05). Conclusion Anemia is associated with subclinical infection in this population, indicating that this is an important variable to be considered in studies of the prevalence of anemia in children. PMID:23284254

Spectral reflectance of the ocular fundus as a diagnostic marker for cerebral malaria

NASA Astrophysics Data System (ADS)

Liu, Xun; Rice, David A.; Khoobehi, Bahram

2012-03-01

The challenge of correctly identifying malaria infection continues to impede our efforts to control this disease. Recent studies report highly specific retinal changes in severe malaria patients; these retinal changes may represent a very useful diagnostic indicator for this disease. To further explore the ocular manifestations of malaria, we used hyperspectral imaging to study retinal changes caused by Plasmodium berghei ANKA parasitization in a mouse model. We collected the spectral reflectance of the ocular fundus from hyperspectral images of the mouse eye. The blood oxygen sensitive spectral region was normalized for variances in illumination, and used to calculate relative values that correspond to oxygenated hemoglobin levels. Oxygen hemoglobin levels are markedly lower in parasitized mice, indicating that hemoglobin digestion by P. berghei may be detected using spectral reflectance. Furthermore, the ocular reflectance of parasitized mice was abnormally elevated between 660nm and 750nm, suggesting fluorescence in this region. While the source of this fluorescence is not yet clear, its presence correlates strongly with P. Berghei parasitization, and may indicate the presence of hemozoin deposits in the retinal vasculature. The pathology of severe malaria still presents many questions for clinicians and scientists, and our understanding of cerebral malaria has been generally confined to clinical observation and postmortem examination. As the retina represents a portion of the central nervous system that can be easily examined noninvasively, our technique may provide the basis for an automated tool to detect and examine severe malaria via retinal changes.

Glomerular Hyperfiltration in Adult Sickle Cell Anemia: A Frequent Hemolysis Associated Feature

PubMed Central

Stankovic, Katia; Levy, Pierre; Avellino, Virginie; Tharaux, Pierre-Louis; Letavernier, Emmanuel; Grateau, Gilles; Baud, Laurent; Girot, Robert; Lionnet, François

2010-01-01

Background and objectives: Sickle cell anemia-associated nephropathy is a growing matter of concern because renal failure affects most aging sickle cell anemia patients. Glomerular damage is a common feature revealed by a microalbuminuria or a macroalbuminuria. Although glomerular hyperfiltration has been described for decades in this population, its prevalence in young adults is unknown. Design, setting, participants, & measurements: To address this issue, as well as the clinical and biologic correlates of hyperfiltration, a single-center, cross-sectional study of 280 homozygous SS disease patients was performed. Results: The prevalence of hyperfiltration assessed by Modification of Diet in Renal Disease estimated GFR was 51%. Among patients with hyperfiltration, 49% had hyperfiltration alone, whereas 36% and 15% had an associated microalbuminuria or macroalbuminuria, respectively. Estimated GFR sensitivity and specificity for hyperfiltration were 94% and 63%, respectively, in a selected subgroup of 48 patients (measured GFR was assessed by urinary 51Cr EDTA clearance). In patients with no albuminuria, hyperfiltration status was significantly associated with a young age (years), the absence of alpha thalassemia, a lower hemoglobin level (g/dl), and a lower fetal hemoglobin. The role of chronic hemolysis was further strengthened by multivariate analysis showing a correlation between estimated GFR and a low plasma fetal hemoglobin level, a young age, and a high reticulocyte count (r2 = 0.54). Conclusions: Together, the data suggest that the pathophysiology of hyperfiltration would rather be attributable to the hemolysis-associated vasculopathy rather than a viscosity-vaso-occlusive process. PMID:20185605

Mean hemoglobin levels in venous blood samples and prevalence of anemia in Japanese elementary and junior high school students.

PubMed

Igarashi, Toru; Itoh, Yasuhiko; Maeda, Miho; Igarashi, Tsutomu; Fukunaga, Yoshitaka

2012-01-01

Screening for anemia has been performed in schools in Japan for over 30 years. The long-term effect of the nuclear power plant disaster on the prevalence of anemia in school age children is unknown. This research was performed to evaluate the prevalence of anemia in school age children and to determine grade-level and gender-related reference hemoglobin (Hb) levels prior to the nuclear disaster. Data for this research were obtained from results of screening for anemia obtained by venous blood sampling in schools in 2002. Mean Hb levels were calculated for each grade level (elementary school grades 1-6 and junior high school years 1-3) and according to gender, and the prevalence of anemia was determined. In our research, Tokyo Health Service Association guidelines were used to determine reference Hb levels for anemia. We demonstrated that Hb levels in boys increased with age during childhood and adolescence (from 13.1 ± 0.7 g/dL in 7 year olds to 14.9 ± 1.1 g/dL in 15 year olds); in girls, Hb levels peaked at menarche (13.7 ± 0.8 g/dL in 12 year olds), decreasing slightly thereafter (13.4 ± 1.1 g/dL in 15 year olds). The prevalence of anemia was 0.26% in elementary school boys, 0.27% in elementary school girls, and 1.21% in junior high school boys. The prevalence of anemia in second- and third-year junior high school girls was lower than that in first-year junior high school girls. Among all junior high school girls, 5.73% had mild anemia. Iron-deficiency anemia is the commonest type of anemia in high school girls, secondary to the relative lack of iron due to menstruation, the growth spurt and exercise. Appropriate dietary therapy and treatment of anemia, together with education about the dietary prevention of anemia, are important to reduce the prevalence of anemia in high school students. When complete blood counts are performed in regions thought to be affected by the Fukushima nuclear power plant disaster, our report can serve as a reference during evaluation of Hb levels.

Patients with sickle cell disease taking hydroxyurea in the Hemocentro Regional de Montes Claros

PubMed Central

Santos, Fernanda Kelle de Souza; Maia, Caroline Nogueira

2011-01-01

Background The development of therapies for sickle cell disease has received special attention, particularly those that reduce the polymerization of hemoglobin S. Hydroxyurea is a commonly used medication because it has the ability to raise levels of fetal hemoglobin, decrease the frequency of vaso-occlusive episodes and thus improve the clinical course of sickle cell disease patients. Objective To study hematological data and the clinical profile of sickle cell disease patients taking hydroxyurea in a regional blood center. Methods From the charts of 20 patients with sickle cell anemia, the clinical outcomes and a number of hematological variables were analyzed before and during treatment with hydroxyurea. Results The patients' ages ranged from 6 to 41 years old, most were dark skinned and there was a predominance of women. The main symptom that defined whether patients were prescribed hydroxyurea was painful crises followed by hospitalizations. During treatment with hydroxyurea there were significant increases in hemoglobin, fetal hemoglobin, mean corpuscular volume and mean corpuscular hemoglobin. The reticulocyte and white blood cell counts dropped significantly with treatment. A positive correlation was found between fetal hemoglobin and mean corpuscular volume before and during treatment. Additionally, a correlation was found between the white blood cell and reticulocyte counts before treatment with hydroxyurea. Conclusion Most patients showed improvements with treatment as demonstrated by increases in hemoglobin, fetal hemoglobin and mean corpuscular volume, as well as by reductions in the reticulocyte and white blood cell counts. Clinically, more than 50% of patients had a significant reduction of events. PMID:23284256

Regulatory Effect of Low-Intensity Optical Radiation on Oxygenation of Blood Irradiated In Vivo and Metabolic Processes

NASA Astrophysics Data System (ADS)

Zalesskaya, G. A.; Laskina, O. V.

2016-03-01

For three series of blood samples, we have studied the effect of therapeutic doses of low-intensity optical radiation (LOR) on oxygenation parameters of blood irradiated in vivo, and also on the levels of some metabolites: lactate, glucose, cholesterol. The quality of blood oxygenation was assessed using three parameters: the partial pressure of oxygen pVO2, the oxygen saturation of hemoglobin SVO2, and the oxygen level in arterial and venous blood, varying under the influence of low-intensity optical radiation due to photodissociation of hemoglobin/ligand complexes. We have established that during photohemotherapy (PHT), including extracorporeal, supravascular, and intravenous blood irradiation, positive changes occur in the oxygenation parameters and the metabolite levels, while after the courses of PHT have been completed, the individual changes in such parameters in individual patients were both positive and negative. The regulatory effect of PHT was apparent in the tendency toward a decrease in high initial values and an increase in low initial values both for the oxygenation parameters and for the metabolites; but at the doses recommended for use, PHT had a regulatory but still not a normalizing effect.

A microfluidic device integrating dual CMOS polysilicon nanowire sensors for on-chip whole blood processing and simultaneous detection of multiple analytes.

PubMed

Kuan, Da-Han; Wang, I-Shun; Lin, Jiun-Rue; Yang, Chao-Han; Huang, Chi-Hsien; Lin, Yen-Hung; Lin, Chih-Ting; Huang, Nien-Tsu

2016-08-02

The hemoglobin-A1c test, measuring the ratio of glycated hemoglobin (HbA1c) to hemoglobin (Hb) levels, has been a standard assay in diabetes diagnosis that removes the day-to-day glucose level variation. Currently, the HbA1c test is restricted to hospitals and central laboratories due to the laborious, time-consuming whole blood processing and bulky instruments. In this paper, we have developed a microfluidic device integrating dual CMOS polysilicon nanowire sensors (MINS) for on-chip whole blood processing and simultaneous detection of multiple analytes. The micromachined polymethylmethacrylate (PMMA) microfluidic device consisted of a serpentine microchannel with multiple dam structures designed for non-lysed cells or debris trapping, uniform plasma/buffer mixing and dilution. The CMOS-fabricated polysilicon nanowire sensors integrated with the microfluidic device were designed for the simultaneous, label-free electrical detection of multiple analytes. Our study first measured the Hb and HbA1c levels in 11 clinical samples via these nanowire sensors. The results were compared with those of standard Hb and HbA1c measurement methods (Hb: the sodium lauryl sulfate hemoglobin detection method; HbA1c: cation-exchange high-performance liquid chromatography) and showed comparable outcomes. Finally, we successfully demonstrated the efficacy of the MINS device's on-chip whole blood processing followed by simultaneous Hb and HbA1c measurement in a clinical sample. Compared to current Hb and HbA1c sensing instruments, the MINS platform is compact and can simultaneously detect two analytes with only 5 μL of whole blood, which corresponds to a 300-fold blood volume reduction. The total assay time, including the in situ sample processing and analyte detection, was just 30 minutes. Based on its on-chip whole blood processing and simultaneous multiple analyte detection functionalities with a lower sample volume requirement and shorter process time, the MINS device can be effectively applied to real-time diabetes diagnostics and monitoring in point-of-care settings.

Comparison of the accuracy of hemoglobin point of care testing using HemoCue and GEM Premier 3000 with automated hematology analyzer in emergency room.

PubMed

Zatloukal, Jan; Pouska, Jiri; Kletecka, Jakub; Pradl, Richard; Benes, Jan

2016-12-01

The laboratory analysis provides accurate, but time consuming hemoglobin level estimation especially in the emergency setting. The reliability of time-sparing point of care devices (POCT) remains uncertain. We tested two POCT devices accuracy (HemoCue ® 201 + and Gem ® Premier™3000) in routine emergency department workflow. Blood samples taken from patients admitted to the emergency department were analyzed for hemoglobin concentration using a laboratory reference Beckman Coulter LH 750 (HB LAB ), the HemoCue (HB HC ) and the Gem Premier 3000 (HB GEM ). Pairwise comparison for each device and Hb LAB was performed using correlation and the Bland-Altman methods. The reliability of transfusion decision was assessed using three-zone error grid. A total of 292 measurements were performed in 99 patients. Mean hemoglobin level were 115 ± 33, 110 ± 28 and 111 ± 30 g/l for Hb HC , Hb GEM and Hb LAB respectively. A significant correlation was observed for both devices: Hb HC versus Hb LAB (r 2  = 0.93, p < 0.001) and HB GEM versus HB LAB (r 2  = 0.86, p < 0.001). The Bland-Altman method revealed bias of -3.7 g/l (limits of agreement -20.9 to 13.5) for HB HC and HB LAB and 2.5 g/l (-18.6 to 23.5) for HB GEM and HB LAB , which significantly differed between POCT devices (p < 0.001). Using the error grid methodology: 94 or 91 % of values (Hb HC and Hb GEM ) fell in the zone of acceptable difference (A), whereas 0 and 1 % (Hb HC and Hb GEM ) were unacceptable (zone C). The absolute accuracy of tested POCT devices was low though reaching a high level of correlation with laboratory measurement. The results of the Morey´s error grid were unfavorable for both POCT devices.

Effect of gamma radiation on the growth, survival, hematology and histological parameters of rainbow trout (Oncorhynchus mykiss) larvae.

PubMed

Oujifard, Amin; Amiri, Roghayeh; Shahhosseini, Gholamreza; Davoodi, Reza; Moghaddam, Jamshid Amiri

2015-08-01

Effects of low (1, 2.5 and 5Gy) and high doses (10, 20 and 40Gy) of gamma radiation were examined on the growth, survival, blood parameters and morphological changes of the intestines of rainbow trout (Oncorhynchus mykiss) larvae (103±20mg) after 12 weeks of exposure. Negative effects of gamma radiation on growth and survival were observed as radiation level and time increased. Changes were well documented at 10 and 20Gy. All the fish were dead at the dose of 40Gy. In all the treatments, levels of red blood cells (RBC), hematocrit (HCT) and hemoglobin (HB) were significantly (P<0.05) declined as the irradiation levels increased, whereas the amount of mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) did not change. No significant differences (P>0.05) were found in the levels of white blood cells (WBC), lymphocytes and monocytes. Destruction of the intestinal epithelium cells was indicated as the irradiation levels increased to 1Gy and above. The highest levels of growth, survival, specific growth rate (SGR), condition factor (CF) and protein efficiency rate (PER) were obtained in the control treatment. The results showed that gamma rays can be a potential means for damaging rainbow trout cells. Copyright © 2015 Elsevier B.V. All rights reserved.

The severity of muscle ischemia during intermittent claudication.

PubMed

Egun, Anselm; Farooq, Vasim; Torella, Francesco; Cowley, Richard; Thorniley, Maureen S; McCollum, Charles N

2002-07-01

The degree of ischemia during intermittent claudication is difficult to quantify. We evaluated calf muscle ischemia during exercise in patients with claudication with near infrared spectroscopy. A Critikon Cerebral Redox Model 2001 (Johnson & Johnson Medical, Newport, Gwent, United Kingdom) was used to measure calf muscle deoxygenated hemoglobin (HHb), oxygenated hemoglobin (O(2)Hb), and total hemoglobin levels and oxygenation index (HbD; HbD = O(2)Hb - HHb) in 16 patients with claudication and in 14 control subjects before, during, and after walking on a treadmill for 1 minute (submaximal exercise). These measures were repeated after a second maximal exercise in patients with claudication and after 7 minutes walking in control subjects. Near-infrared spectroscopy readings during maximal exercise were then compared with a model of total ischemia induced with tourniquet in 16 young control subjects. Total hemoglobin level changed little during exercise in both patients with claudication and control subjects. HHb levels rose, and O(2)Hb level and HbD falls were more pronounced in patients with claudication than in control subjects after submaximal and maximal exercise. During maximal exercise, HbD fell markedly by a median (interquartile range) of 210.5 micromol/cm (108.2 to 337.0 micromol/cm) in patients with claudication compared with 66.0 micromol/cm (44.0 to 101.0 micromol/cm) in elderly control subjects and 41.0 micromol/cm (36.0 to 65.0 micromol/cm) in young control subjects (P <.001). This fall also was greater than the HbD fall induced with tourniquet ischemia at 90.8 micromol/cm (57.6 to 126.2 micromol/cm; P =.006). Hemoglobin desaturation in exercising calf muscle is profound in patients with claudication, considerably greater even than that induced with three minutes of tourniquet occlusion. Further studies are necessary to investigate the relationship between the inflammatory response and near-infrared spectroscopy during exercise in patients with claudication.

Configuration of the Hemoglobin Oxygen Dissociation Curve Demystified: A Basic Mathematical Proof for Medical and Biological Sciences Undergraduates

ERIC Educational Resources Information Center

Leow, Melvin Khee-Shing

2007-01-01

The oxygen dissociation curve (ODC) of hemoglobin (Hb) has been widely studied and mathematically described for nearly a century. Numerous mathematical models have been designed to predict with ever-increasing accuracy the behavior of oxygen transport by Hb in differing conditions of pH, carbon dioxide, temperature, Hb levels, and…

Residual blood processing by centrifugation, cell salvage or ultrafiltration in cardiac surgery: effects on clinical hemostatic and ex-vivo rheological parameters.

PubMed

Vonk, Alexander B; Muntajit, Warayouth; Bhagirath, Pranav; van Barneveld, Laurentius J; Romijn, Johannes W; de Vroege, Roel; Boer, Christa

2012-10-01

The study compared the effects of three blood concentration techniques after cardiopulmonary bypass on clinical hemostatic and ex-vivo rheological parameters. Residual blood of patients undergoing elective cardiac surgery was processed by centrifugation, cell salvage or ultrafiltration, and retransfused (n = 17 per group). Study parameters included blood loss, (free) hemoglobin, hematocrit, fibrinogen and erythrocyte aggregation, deformability and 2,3-diphosphoglycerate content. Patient characteristics were similar between groups. Ultrafiltration was associated with the highest weight of the transfusion bag [649 ± 261 vs. 320 ± 134 g (centrifugation) and 391 ± 158 g (cell salvage); P < 0.01]. Cell salvage resulted in the lowest hemolysis levels in the transfusion bag. Retransfusion of cell saver blood induced the largest gain in postoperative patient hemoglobin levels when compared to centrifugation and ultrafiltration, and was associated with the largest increase in 2,3-diphosphoglycerate when compared to ultrafiltration (Δ2,3-diphosphoglycerate 1.34 ± 1.92 vs. -0.77 ± 1.56 mmol/l; P = 0.03). Cell salvage is superior with respect to postoperative hemoglobin gain and washout of free hemoglobin when compared to centrifugation or ultrafiltration.

Overproduction of alpha chains provides a proton-insensitive component to the bluefish hemoglobin system.

PubMed

Bonaventura, Celia; Godette, Gerald; Stevens, Robert; Brenowitz, Michael; Henkens, Robert

2005-12-09

Expression of alpha and beta chains and their post-translational assembly into alpha(2)beta(2) tetramers is fundamental to the formation and function of most vertebrate hemoglobins. There is a strong evolutionary bias that favors expression of equal amounts of the two types of chains, because cooperativity, pH sensitivity, and anionic control of function occurs only for the alpha(2)beta(2) tetramers. Remarkably, an over-production of alpha chains, as in the pathological condition known as beta thalassemia in humans, is adaptive rather than pathological in the bluefish hemoglobin system. The thalassemia of the bluefish is a novel means of providing for oxygen uptake and delivery when low pH conditions incapacitate the highly pH-sensitive Root effect hemoglobins of the fish. Although fish often have pH-insensitive along with highly pH-sensitive hemoglobins, having pH-insensitive alpha chain monomers in circulation is an unusual structural variation. The role of bluefish alpha chains in oxygen transport is enabled by their remarkably lower oxygen affinity relative to human alpha chains. This is the first reported case of a thalassemic condition that is maintained in a species as an adaptive advantage.

Method of acetaldehyde measurement with minimal artifactual formation in red blood cells and plasma of actively drinking subjects with alcoholism.

PubMed

Hernandez-Munoz, R; Ma, X L; Baraona, E; Lieber, C S

1992-07-01

After alcohol consumption, a substantial amount of acetaldehyde that is reversibly bound to protein and nonprotein components of the red blood cells circulates in the blood and could cause extrahepatic toxicity. However, acetaldehyde measurement in human red blood cells is hampered by considerable ex vivo artifactual formation as a result of nonenzymatic oxidation of ethanol during protein precipitation. To eliminate this source of artifactual formation, free and reversibly bound acetaldehyde were trapped with semicarbazide from red blood cell hemolysates, and both the stroma and the hemoglobin were sequentially removed by centrifugation and ion-exchange chromatography in carboxymethyl Sephadex, respectively. The eluted semi-carbazone was dissociated with perchloric acid, and the acetaldehyde that was released in the protein-free supernatants was measured by head-space gas chromatography. Maximal retention of hemoglobin by carboxymethyl Sephadex and complete recovery of acetaldehyde and ethanol were achieved at a pH of 5.3. The artifactual formation decreased from 2.62 +/- 0.32 mumol of acetaldehyde per millimole of ethanol in the initial hemolysates to 1.38 +/- 0.20 mumol after removal of the stroma and to a level that is comparable to measurements in plasma (0.09 +/- 0.02 mumol) after removal of both the stroma and the hemoglobin. In 12 actively drinking subjects with alcoholism, with blood ethanol levels that ranged between 9 and 81 mmol/L, the concentrations of acetaldehyde in red blood cells (11.50 +/- 1.46 mumol/L; range: 7.5 to 22 mumol/L) were minimally affected by blood ethanol levels and were three times as high as those in the plasma (3.74 +/- 1.49 mumol/L).(ABSTRACT TRUNCATED AT 250 WORDS)

A randomized, placebo-controlled, crossover study of an herbal preparation containing Vernonia cinerea in the treatment of type 2 diabetes.

PubMed

Bin Sayeed, Muhammad Shahdaat; Mostofa, A G M; Ferdous, F M Touhidul Islam; Islam, Md Siddiqul

2013-09-01

A randomized, single-center, double-blind, crossover clinical trial investigated the effects of an herbal preparation containing Vernonia cinerea in patients with type 2 diabetes mellitus. 48 patients with type 2 diabetes mellitus for longer than 6 months were divided into two groups matched for demographic and paraclinical variables. One group received a standard preparation of V. cinerea for 3 months, followed by placebo for another 3 months, and the other group received treatment in the reverse order. All patients received detailed advice on diet, exercise, and lifestyle modification. Glucose level was documented every 2 weeks, and hemoglobin A1c, total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein cholesterol, triglycerides, aspartate aminotransferase, alanine aminotransferase, and creatinine levels were determined at recruitment, 3 months, and study completion at 6 months. Glucose, hemoglobin A1c, cholesterol, LDL cholesterol, and triglyceride levels decreased significantly in both groups. No significant differences were seen in aspartate aminotransferase, alanine aminotransferase, or creatinine levels, indicating that use of the herbal preparation had no adverse effect on liver or renal function. Herbal treatment with V. cinerea has a beneficial effect on reducing the glycemic state in patients with type 2 diabetes.

EVALUATION AND MANAGEMENT OF ANEMIA IN THE ELDERLY

PubMed Central

Goodnough, Lawrence Tim; Schrier, Stanley L.

2015-01-01

Anemia is now recognized as a risk factor for a number of adverse outcomes in the elderly, including hospitalization, morbidity, and mortality. What constitutes appropriate evaluation and management for an elderly patient with anemia, and when to initiate a referral to a hematologist, are significant issues. Attempts to identify suggested hemoglobin levels for blood transfusion therapy have been confounded for elderly patients with their co-morbidities. Since no specific recommended hemoglobin threshold has stood the test of time, prudent transfusion practices to maintain hemoglobin thresholds of 9–10 g/dl in the elderly are indicated, unless or until evidence emerges to indicate otherwise. PMID:24122955

Hemoglobins emerging roles in mental disorders. Metabolical, genetical and immunological aspects.

PubMed

Altinoz, Meric A; Ince, Bahri

2017-10-01

Hemoglobin (Hb) expression in the central nervous system is recently shown. Cooccurences of mental disorders (mainly bipolar disorder (BD) and tic disorders) with β- or α-thalassemia trait or erythrocytosis were witnessed, which may be due to peripheral or central hypoxia/hyperoxia or haplotypal gene interactions. β-Globin genes reside at 11p15.5 close to tyrosine hydroxylase, dopamine receptor DRD4 and Brain Derived Neurotrophic Factor, which involve in psychiatric diseases. α-Globin genes reside at 16p13.3 which associates with BD, tic disorders, ATR-16 Syndrome and Rubinstein Taybi Syndrome (RTS). CREB-Binding Protein (CEBBP)-gene is mutated in RTS, which commonly associates with mood disorders. 16p13.3 region also contains GRIN2A gene encoding N-methyl-d-aspartate receptor-2A and SSTR5 (Somatostatin Receptor-5), again involving in mental disorders. We demonstrated a protective role of minor HbA2 against post-partum episodes in BD and association of higher minor HbF (fetal hemoglobin) levels with family history of psychosis in a BD-patient cohort. HbA2 increases in cardiac ischemia and in mountain dwellers indicating its likely protection against ischemia/hypoxia. HMGIY, a repressive transcription factor of δ-globin chain of HbA2 is increased in lymphocytes of schizophrenics. In autism, deletional mutations were found in BCL11A gene, which cause persistence of HbF at high levels in adulthood. Also, certain polymorphisms in BCL11A strongly associate with schizophrenia. Further, many drugs from anabolic steroids to antimalarial agents elevate HbF and may cause mania. We ascribe a protective role to HbA2 and a maladaptive detrimental role to HbF in psychopathology. We believe that future studies on hemoglobins may pave to discover novel pathogenesis mechanisms in mental disorders. Copyright © 2017 ISDN. Published by Elsevier Ltd. All rights reserved.

Oxygen binding properties of hemoglobin from the white rhinoceros (beta 2-GLU) and the tapir.

PubMed

Baumann, R; Mazur, G; Braunitzer, G

1984-04-01

The beta-chain of rhinoceros hemoglobin contains glutamic acid at position beta 2, and important site for the binding of organic phosphates. We have investigated the oxygen binding properties of this hemoglobin and its interaction with ATP, 2,3-diphosphoglycerate, CO2 and chloride. The results show that the presence of GLU at position beta 2 nearly abolishes the effect of organic phosphates and CO2, whereas the oxygen-linked binding of chloride is not affected. Thus rhinoceros hemoglobin has only protons and chloride anions as major allosteric effectors for the control of its oxygen affinity. From the results obtained with hemoglobin solutions it can be calculated that the blood oxygen affinity of the rhinoceros must be rather high with a P50 of about 20 torr at pH 7.4 and 37 degrees C, which conforms with observations obtained for other large mammals.

Color stabilization of porcine hemoglobin during spray-drying and powder storage by combining chelating and reducing agents.

PubMed

Salvador, P; Toldrà, M; Parés, D; Carretero, C; Saguer, E

2009-10-01

This work focuses on the effects of adding a chelating agent - such as nicotinic acid (NA, 2% w/v) or nicotinamide (Nam, 2.5% w/v) - along with glucose as a reducing agent (G, 10% w/v) to fresh porcine hemoglobin in order to stabilize its red color during spray-drying and powder storage at room temperature. Correlations between the CIELAB color parameters and the relative percentages of the different hemoglobin derivatives (liganded and deliganded ferrohemoglobin, and methemoglobin) were analyzed. The results indicate that, although little effects could be observed for any of the combined treatments on fresh hemoglobin, they were effective against pigment autoxidation during dehydration and subsequent storage. From the results, it can also be concluded that glucose was the main contributor to the color stabilization of the hemoglobin powder, probably due to its high water retention capacity.

Effect of high protein vs high carbohydrate intake on insulin sensitivity, body weight, hemoglobin A1c, and blood pressure in patients with type 2 diabetes mellitus.

PubMed

Sargrad, Karin R; Homko, Carol; Mozzoli, Maria; Boden, Guenther

2005-04-01

Extremely low carbohydrate/high protein diets are popular methods of weight loss. Compliance with these diets is poor and long-term effectiveness and the safety of these diets for patients with type 2 diabetes is not known. The objective of the current study was to evaluate effects of less extreme changes in carbohydrate or protein diets on weight, insulin sensitivity, glycemic control, cardiovascular risk factors (blood pressure, lipid levels), and renal function in obese inner-city patients with type 2 diabetes. Study patients were admitted to the General Clinical Research Center for 24 hours for initial tests including a hyperinsulinemic-euglycemic clamp (for measurement of insulin sensitivity), bioelectrical impedance analysis (BIA) and anthropometric measurements (for assessment of body composition), indirect calorimetry (for measurement of REE), electronic blood pressure monitoring, and blood chemistries to measure blood lipids levels along with renal and hepatic functions. Six patients with type 2 diabetes (five women and one man) were randomly assigned to the high-protein diet (40% carbohydrate, 30% protein, 30% fat) and six patients (four women and two men) to the high-carbohydrate diet (55% carbohydrate, 15% protein, 30% fat). All patients returned to the General Clinical Research Center weekly for monitoring of food records; dietary compliance; and measurements of body weight, blood pressure, and blood glucose. After 8 weeks on these diets, all patients were readmitted to the General Clinical Research Center for the same series of tests. Twelve study patients were taught to select either the high-protein or high-carbohydrate diet and were followed for 8 weeks. Insulin sensitivity, hemoglobin A1c, weight, and blood pressure were measured. Statistical significance was assessed using two-tailed Student's t tests and two-way repeated measures analysis of variance. Both the high-carbohydrate and high-protein groups lost weight (-2.2+/-0.9 kg, -2.5+/-1.6 kg, respectively, P <.05) and the difference between the groups was not significant (P =.9). In the high-carbohydrate group, hemoglobin A1c decreased (from 8.2% to 6.9%, P <.03), fasting plasma glucose decreased (from 8.8 to 7.2 mmol/L, P <.02), and insulin sensitivity increased (from 12.8 to 17.2 micromol/kg/min, P <.03). No significant changes in these parameters occurred in the high-protein group, instead systolic and diastolic blood pressures decreased (-10.5+/-2.3 mm Hg, P =.003 and -18+/-9.0 mm Hg, P <.05, respectively). After 2 months on these hypocaloric diets, each diet had either no or minimal effects on lipid levels (total cholesterol, low-density lipoprotein, high-density lipoprotein), renal (blood urea nitrogen, serum creatinine), or hepatic function (aspartate aminotransferase, alanine aminotransferase, bilirubin).

Double-blind randomized controlled trial of rolls fortified with microencapsulated iron.

PubMed

Barbosa, Teresa Negreira Navarro; Taddei, José Augusto de Aguiar Carrazedo; Palma, Domingos; Ancona-Lopez, Fábio; Braga, Josefina Aparecida Pellegrini

2012-01-01

To evaluate the impact of the fortification of rolls with microencapsulated iron sulfate with sodium alginate on the hemoglobin levels in preschoolers as compared to controls. Double-blind randomized controlled trial comprised of children aged 2 to 6 years with initial hemoglobin exceeding 9 g/dL from four not-for-profit daycares randomly selected in the city of São Paulo - Brazil. Children of 2 daycares (n = 88) received rolls with fortified wheat flour as the exposed group (EC) and children of 2 daycares (n = 85) received rolls without fortification as the control group (CG) over a 24-week period. Rolls with 4 mg iron each were offered once a day, five days a week. Hemoglobin concentrations were determined in capillary blood by HemoCue® at three moments of trial: baseline (Ml), after 12 and 24 weeks of intervention (M2, M3). Hemoglobin concentration presented significant increase up to M3 in EG (11.7-12.5-12.6 g/dL) and in CG (11.1-12.4-12.3 g/dL) with higher elevations in children initially with anemia. There was significant reduction in the occurrence of anemia from 22% to 9% in EG and from 47% to 8.2% in CG at M3. Rolls fortified with microencapsulated iron sulfate were well tolerated, increased hemoglobin levels and reduced the occurrence of anemia, but with no difference compared to the control group.

Effects of sounds generated by a dental turbine and a stream on regional cerebral blood flow and cardiovascular responses.

PubMed

Mishima, Riho; Kudo, Takumu; Tsunetsugu, Yuko; Miyazaki, Yoshifumi; Yamamura, Chie; Yamada, Yoshiaki

2004-09-01

Effects of sound generated by a dental turbine and a small stream (murmur) and the effects of no sound (null, control) on heart rate, systolic and diastolic blood pressure, and hemodynamic changes (oxygenated, deoxygenated, and total hemoglobin concentrations) in the frontal cortex were measured in 18 young volunteers. Questionnaires completed by the volunteers were also evaluated. Near-infrared spectroscopy and the Finapres technique were employed to measure hemodynamic and vascular responses, respectively. The subjects assessed the murmur, null, and turbine sounds as "pleasant," "natural," and "unpleasant," respectively. Blood pressures changed in response to the murmur, null, and turbine sound stimuli as expected: lower than the control level, unchanged, and higher than the control level, respectively. Mean blood pressure values tended to increase gradually over the recording time even during the null sound stimulation, possibly because of the recording environment. Oxygenated hemoglobin concentrations decreased drastically in response to the dental turbine sound, while deoxygenated hemoglobin concentrations remained unchanged and thus total hemoglobin concentrations decreased (due to the decreased oxygenated hemoglobin concentrations). Hemodynamic responses to the murmuring sound and the null sound were slight or unchanged, respectively. Surprisingly, heart rate measurements remained fairly stable in response to the stimulatory noises. In conclusion, we demonstrate here that sound generated by a dental turbine may affect cerebral blood flow and metabolism as well as autonomic responses. Copyright 2004 The Society of the Nippon Dental University

[Interest of the study of a not identified peak on a hemoglobin chromatogram: delta variant or inter-sample contaminations?].

PubMed

Desmons, Aurore; Jaisson, Stéphane; Gillery, Philippe; Guillard, Emmanuelle

2013-01-01

D-10(®) (Bio-Rad) analyzer using cationic exchange high performance chromatography (HPLC) allows the detection of the main hemoglobin variants. This observation shows the presence of a peak on chromatogram with a low intensity and no quantifiable which can lead to different diagnosis. Inter-sample contaminations can be confused with the presence of an hemoglobin variant. This case highlights the importance of the knowledge of technicals limits for validation and clinical use of results.

Noninvasive monitoring of cerebral oxygenation in preterm infants: preliminary observations.

PubMed

Brazy, J E; Lewis, D V; Mitnick, M H; Jöbsis vander Vliet, F F

1985-02-01

A noninvasive optical method for bedside monitoring of cerebral oxygenation in small preterm infants was evaluated. Through differential absorbance of near infrared light, changes in the oxidation-reduction level of cytochrome aa3, in the oxygenation state of hemoglobin and in tissue blood volume were assessed in the transilluminated anterior cerebral field. Overall, cerebral oxygenated hemoglobin correlated significantly with transcutaneous oxygen, r = .44 p less than .0001; however, correlation was best in the absence of cardiorespiratory disease. Hypoxia with or without bradycardia led to hemoglobin deoxygenation and a shift in cytochrome aa3 to a more reduced state. When hypoxic episodes came in series or were prolonged, aa3 reduction occurred simultaneous with hemoglobin deoxygenation but its recovery to base-line values sometimes lagged behind the return of hemoglobin oxygenation. In one infant with a large patent ductus arteriosus, even brief episodes of mild bradycardia caused precipitous reduction of cytochrome aa3 before any shift to greater hemoglobin deoxygenation. This response disappeared after ductal ligation. In general, the antecedent state of cerebral oxygenation, the severity and duration of deoxygenation, and the presence or absence of circulatory abnormalities all influenced the aa3 response to hypoxia. Continuous noninvasive near infrared monitoring of cerebral oxygenation can be performed on sick preterm infants at the bedside.

Extended-release niacin treatment of the atherogenic lipid profile and lipoprotein(a) in diabetes.

PubMed

Pan, Jianqiu; Van, Joanne T; Chan, Eve; Kesala, Renata L; Lin, Michael; Charles, M Arthur

2002-09-01

We tested the hypotheses that extended-release niacin is effective for the separate treatments of abnormalities in low-density liprotein (LDL) size, high-density lipoprotein (HDL)-2, and lipoprotein(a) [Lp(a)] without potential negative effects on glycated hemoglobin levels. The lipids that constitute the atherogenic lipid profile (ALP), such as triglycerides, small, dense LDL-cholesterol particle concentration, LDL particle size, total HDL-cholesterol (HDLc), HDL-2, and HDL-2 cholesterol concentration, as well as total LDL-cholesterol (LDLc) and Lp(a), were measured in 36 diabetic patients with primary abnormalities of LDL particle size (n = 25), HDL-2 (n = 23), and/or Lp(a) (n = 12) before and after extended-release niacin treatment. LDL particle size and HDL-2 were measured using polyacrylamide gradient gel electrophoreses and Lp(a) was measured by enzyme-linked immunosorbent assay (ELISA). After extended-release niacin, LDL peak particle diameter increased from 25.2 +/- 0.6 nm to 26.1 +/- 0.7 nm (P <.0001); small, dense LDLc concentration decreased from 30 +/- 17 mg/dL to 17 +/- 10 mg/dL (P <.0001); total HDLc increased from 42 +/- 9 mg/dL to 57 +/- 16 mg/dL (P <.0001); HDL-2 as the percent of total HDLc mass increased from 34% +/- 10% to 51% +/- 17% (P <.0001); and Lp(a) decreased from 37 +/- 10 mg/dL to 23 +/- 10 mg/dL (P <.001). Mean hemoglobin A(1c) level was improved during treatment from 7.5% +/- 1.6% to 6.5% +/- 0.9% (P <.0001). A subset of patients who had no change in hemoglobin A(1c) levels before and after treatment (6.8% +/- 1% v 6.7% +/- 1%; not significant) showed identical lipid changes. Twenty-two percent of patients were unable to tolerate extended-release niacin due to reversible side effects. These data indicate that in diabetic patients, extended-release niacin (1) is effective for separately treating diabetic dyslipidemias associated with abnormal LDL size, HDL-2, and Lp(a) independently of glycated hemoglobin levels; (2) must be used with modern and aggressive oral hypoglycemic agents or insulin treatment; and (3) is a major drug for the treatment of diabetic dyslipidemias because of its broad spectrum of effectiveness for the ALP and Lp(a). Copyright 2002, Elsevier Science (USA). All rights reserved.

Cigarette smoking reduces platelet reactivity independently of clopidogrel treatment in patients with non-ST elevation acute coronary syndromes.

PubMed

Crimi, Gabriele; Somaschini, Alberto; Cattaneo, Marco; Angiolillo, Dominick J; Piscione, Federico; Palmerini, Tullio; De Servi, Stefano

2018-05-01

Smokers receiving clopidogrel show a lower residual platelet reactivity than non-smokers, a phenomenon generally ascribed to smoking-induced increased production of clopidogrel active metabolite, but also associated with the high hemoglobin levels of smokers, which decreases platelet reactivity in tests that measure platelet function in whole blood. We evaluated the impact of cigarette smoking and of hemoglobin levels on platelet reactivity index (PRI) measured by the vasodilator-stimulated phosphoprotein phosphorylation (VASP-P) assay in whole blood samples from patients with non-ST elevation acute coronary syndrome (NSTE-ACS) undergoing percutaneous coronary interventions, both before and after clopidogrel administration. PRI was measured in 718 clopidogrel-naïve NSTE-ACS patients, both before and 1 month after treatment with clopidogrel (75 mg daily). Smokers (n = 347, 48%) had significantly lower mean PRI levels at both baseline (57.7 ± 24.1 vs. 64.8 ± 19.8, p < 0.001) and 1 month (43.4 ± 20.3% vs. 46.8 ± 18.0%, p = 0.017) than non-smokers. After adjusting for potential confounders (age, sex, diabetes, chronic kidney disease, Syntax score>15), the β coefficient of smoke on PRI was -8.51 [-11.90 to -5.11, p < 0.001] at baseline and -3.41 [-6.30 to -0.51, p = 0.02] after 1 month. Hemoglobin was higher in smokers (13.8 ± 1.5 g/dL) than non-smokers (13.1 ± 1.7 g/dL, p < 0.001), but was not significantly correlated with PRI both at baseline (Rho = 0.02, p = 0.60) and at 1 month (Rho = 0.01, p = 0.80). Our analysis confirms that clopidogrel-treated smokers have lower platelet reactivity, measured by the VASP-P assay, compared to clopidogrel-treated non-smokers. However, smokers had lower platelet reactivity already before receiving clopidogrel treatment, suggesting that smoke affects platelet reactivity independently of its potential effect on the pharmacokinetics of clopidogrel. Our data also indicate that such an effect is not mediated by increased hemoglobin levels.

Delayed-Onset Hemolytic Anemia in Patients with Travel-Associated Severe Malaria Treated with Artesunate, France, 2011–2013

PubMed Central

Thellier, Marc; Ndour, Papa Alioune; Ader, Flavie; Roussel, Camille; Sonneville, Romain; Mayaux, Julien; Matheron, Sophie; Angoulvant, Adela; Wyplosz, Benjamin; Rapp, Christophe; Pistone, Thierry; Lebrun-Vignes, Bénédicte; Kendjo, Eric; Danis, Martin; Houzé, Sandrine; Bricaire, François; Mazier, Dominique; Buffet, Pierre; Caumes, Eric

2015-01-01

Artesunate is the most effective treatment for severe malaria. However, delayed-onset hemolytic anemia has been observed in ≈20% of travelers who receive artesunate, ≈60% of whom require transfusion. This finding could discourage physicians from using artesunate. We prospectively evaluated a cohort of 123 patients in France who had severe imported malaria that was treated with artesunate; our evaluation focused on outcome, adverse events, and postartesunate delayed-onset hemolysis (PADH). Of the 123 patients, 6 (5%) died. Overall, 97 adverse events occurred. Among the 78 patients who received follow-up for >8 days after treatment initiation, 76 (97%) had anemia, and 21 (27%) of the 78 cases were recorded as PADH. The median drop in hemoglobin levels was 1.3 g/dL; 15% of patients with PADH had hemoglobin levels of <7 g/dL, and 1 required transfusion. Despite the high incidence of PADH, the resulting anemia remained mild in 85% of cases. This reassuring result confirms the safety and therapeutic benefit of artesunate. PMID:25898007

Characteristics and clinical correlates of MPL 515W>L/K mutation in essential thrombocythemia.

PubMed

Vannucchi, Alessandro M; Antonioli, Elisabetta; Guglielmelli, Paola; Pancrazzi, Alessandro; Guerini, Vittoria; Barosi, Giovanni; Ruggeri, Marco; Specchia, Giorgina; Lo-Coco, Francesco; Delaini, Federica; Villani, Laura; Finotto, Silvia; Ammatuna, Emanuele; Alterini, Renato; Carrai, Valentina; Capaccioli, Gloria; Di Lollo, Simonetta; Liso, Vincenzo; Rambaldi, Alessandro; Bosi, Alberto; Barbui, Tiziano

2008-08-01

Among 994 patients with essential thrombocythemia (ET) who were genotyped for the MPLW515L/K mutation, 30 patients carrying the mutation were identified (3.0%), 8 of whom also displayed the JAK2V671F mutation. MPLW515L/K patients presented lower hemoglobin levels and higher platelet counts than did wild type (wt) MPL; these differences were highly significant compared with MPLwt/JAK2V617F-positive patients. Reduced hemoglobin and increased platelet levels were preferentially associated with the W515L and W515K alleles, respectively. MPL mutation was a significant risk factor for microvessel disturbances, suggesting platelet hyperreactivity associated with constitutively active MPL; arterial thromboses were increased only in comparison to MPLwt/JAK2wt patients. MPLW515L/K patients presented reduced total and erythroid bone marrow cellularity, whereas the numbers of megakaryocytes, megakaryocytic clusters, and small-sized megakaryocytes were all significantly increased. These data indicate that MPLW515L/K mutations do not define a distinct phenotype in ET, although some differences depended on the JAK2V617F mutational status of the counterpart.

DOE Office of Scientific and Technical Information (OSTI.GOV)

de Alarcon, P.A.; Donovan, M.E.; Forbes, G.B.

To determine the hemoglobin concentration at which iron absorption is minimal, five subjects with thalassemia major and one with thalassemia intermedia underwent a series of iron-absorption studies. The effect of tea as an inhibitor of non-heme iron absorption was also tested. Iron absorption increased as the hemoglobin concentration decreased, although iron absorption was much higher at any given hemoglobin level in the subject with thalassemia intermedia. In the subjects with thalassemia major, iron absorption averaged 10% at hemoglobin concentrations between 9 and 10 and 2.7 per cent between 11 and 13 g per deciliter. The percentage of iron absorbed couldmore » be accurately predicted from the nucleated red-cell count (r = 0.91, P < 0.001). Tea produced a 41 to 95% inhibition of iron absorption. Since patients with thalassemia intermedia may absorb a large percentage of dietary iron, inhibitors of iron absorption, such as tea, may be useful in their management.« less

Nitric Oxide in Plants: The Roles of Ascorbate and Hemoglobin

PubMed Central

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 concentration does not impact 3-month outcome following acute ischemic stroke.

PubMed

Sharma, Kartavya; Johnson, Daniel J; Johnson, Brenda; Frank, Steven M; Stevens, Robert D

2018-06-02

There is uncertainty regarding the effect of anemia and red blood cell transfusion on functional outcome following acute ischemic stroke. We studied the relationship of hemoglobin parameters and red cell transfusion with post stroke functional outcome after adjustment for neurological severity and medical comorbidities. Retrospective cohort study of 536 patients discharged with a diagnosis of ischemic stroke from a tertiary care hospital between January 2012 and April 2015. Hemoglobin level at hospital admission, lowest recorded value during hospitalization (nadir), delta hemoglobin (admission minus nadir), red cell transfusion during hospitalization were noted. Charlson Comorbidity Index (CCI) was computed as a summary measure of medical comorbidities. A multivariable logistic regression model was used to determine risk-adjusted odds of unfavorable outcome, defined as a modified Rankin Score of > 2. Anemia was present on hospital admission in 31% of patients. Forty five percent of patients had unfavorable outcome. In the univariable analysis increasing age, admission National Institutes of Health Stroke Scale (NIHSS), CCI, nadir hemoglobin, delta hemoglobin and blood transfusion were associated with unfavorable outcome. In the multivariable model, only increasing age, CCI and NIHSS remained associated with unfavorable outcome. No quadratic association was found on repeating the model to identify a possible U-shaped relationship of hemoglobin with outcome. Our findings contradict prior observational studies and highlight an area of clinical equipoise regarding the optimal management of anemia in patients hospitalized for ischemic stroke. This uncertainty could be addressed with appropriately designed clinical trials.

[The effect of vegetarian diet on selected biochemical and blood morphology parameters].

PubMed

Nazarewicz, Rafał

2007-01-01

The objective was to examine whether vegetarian diet influence biochemical parameters of blood and plasma urea in selective vegetarian group. The investigation covered 41 subject, 22 of them had been applying vegetarian diet and 19 were omnivorous. The study shows statistically significant lower values of white blood cells, % and amounts of neutrocytes and insignificant lower level of red blood cells, hemoglobine, hematocrit and platelet in vegetarian group. Significant lower plasma urea level was observed in that group. These changes indicate that high quality deficiency protein was due to vegetarian diet.

Computational Model for Tumor Oxygenation Applied to Clinical Data on Breast Tumor Hemoglobin Concentrations Suggests Vascular Dilatation and Compression.

PubMed

Welter, Michael; Fredrich, Thierry; Rinneberg, Herbert; Rieger, Heiko

2016-01-01

We present a computational model for trans-vascular oxygen transport in synthetic tumor and host tissue blood vessel networks, aiming at qualitatively explaining published data of optical mammography, which were obtained from 87 breast cancer patients. The data generally show average hemoglobin concentration to be higher in tumors versus host tissue whereas average oxy-to total hemoglobin concentration (vascular segment RBC-volume-weighted blood oxygenation) can be above or below normal. Starting from a synthetic arterio-venous initial network the tumor vasculature was generated by processes involving cooption, angiogenesis, and vessel regression. Calculations of spatially resolved blood flow, hematocrit, oxy- and total hemoglobin concentrations, blood and tissue oxygenation were carried out for ninety tumor and associated normal vessel networks starting from various assumed geometries of feeding arteries and draining veins. Spatial heterogeneity in the extra-vascular partial oxygen pressure distribution can be related to various tumor compartments characterized by varying capillary densities and blood flow characteristics. The reported higher average hemoglobin concentration of tumors is explained by growth and dilatation of tumor blood vessels. Even assuming sixfold metabolic rate of oxygen consumption in tumorous versus host tissue, the predicted oxygen hemoglobin concentrations are above normal. Such tumors are likely associated with high tumor blood flow caused by high-caliber blood vessels crossing the tumor volume and hence oxygen supply exceeding oxygen demand. Tumor oxy- to total hemoglobin concentration below normal could only be achieved by reducing tumor vessel radii during growth by a randomly selected factor, simulating compression caused by intra-tumoral solid stress due to proliferation of cells and extracellular matrix. Since compression of blood vessels will impede chemotherapy we conclude that tumors with oxy- to total hemoglobin concentration below normal are less likely to respond to chemotherapy. Such behavior was recently reported for neo-adjuvant chemotherapy of locally advanced breast tumors.

Computational Model for Tumor Oxygenation Applied to Clinical Data on Breast Tumor Hemoglobin Concentrations Suggests Vascular Dilatation and Compression

PubMed Central

Welter, Michael; Fredrich, Thierry; Rinneberg, Herbert; Rieger, Heiko

2016-01-01

We present a computational model for trans-vascular oxygen transport in synthetic tumor and host tissue blood vessel networks, aiming at qualitatively explaining published data of optical mammography, which were obtained from 87 breast cancer patients. The data generally show average hemoglobin concentration to be higher in tumors versus host tissue whereas average oxy-to total hemoglobin concentration (vascular segment RBC-volume-weighted blood oxygenation) can be above or below normal. Starting from a synthetic arterio-venous initial network the tumor vasculature was generated by processes involving cooption, angiogenesis, and vessel regression. Calculations of spatially resolved blood flow, hematocrit, oxy- and total hemoglobin concentrations, blood and tissue oxygenation were carried out for ninety tumor and associated normal vessel networks starting from various assumed geometries of feeding arteries and draining veins. Spatial heterogeneity in the extra-vascular partial oxygen pressure distribution can be related to various tumor compartments characterized by varying capillary densities and blood flow characteristics. The reported higher average hemoglobin concentration of tumors is explained by growth and dilatation of tumor blood vessels. Even assuming sixfold metabolic rate of oxygen consumption in tumorous versus host tissue, the predicted oxygen hemoglobin concentrations are above normal. Such tumors are likely associated with high tumor blood flow caused by high-caliber blood vessels crossing the tumor volume and hence oxygen supply exceeding oxygen demand. Tumor oxy- to total hemoglobin concentration below normal could only be achieved by reducing tumor vessel radii during growth by a randomly selected factor, simulating compression caused by intra-tumoral solid stress due to proliferation of cells and extracellular matrix. Since compression of blood vessels will impede chemotherapy we conclude that tumors with oxy- to total hemoglobin concentration below normal are less likely to respond to chemotherapy. Such behavior was recently reported for neo-adjuvant chemotherapy of locally advanced breast tumors. PMID:27547939

Factors influencing brain natriuretic peptide levels in healthy pregnant women.

PubMed

Mayama, Michinori; Yoshihara, Masato; Uno, Kaname; Tano, Sho; Takeda, Takehiko; Ukai, Mayu; Kishigami, Yasuyuki; Oguchi, Hidenori

2017-02-01

The normal range of plasma brain natriuretic peptide (BNP) in pregnant women is still unclear. Moreover, pregnant women experience dynamic body weight changes and suffer from anemia, but effects on maternal BNP have not been investigated. This study aimed to reveal the normal plasma BNP range and examine the effects of physiological changes on BNP among pregnant women. Plasma BNP, hemoglobin, plasma creatinine and BMI were measured in 58 non-pregnant control women and in 773 normal pregnant women at late pregnancy, early postpartum and 1-month postpartum. Mean plasma BNP (in pg/mL) was 11.8 (95% confidence interval: 0-27.5) in non-pregnant women, 17.9 (0-44.7, p<0.001) at late pregnancy, 42.5 (0-112.6, p<0.001) early postpartum and 16.1 (0-43.9, p=0.001) 1-month postpartum. Multiple regression analysis revealed that pre-delivery BNP levels were negatively correlated with BMI (p<0.001) and hemoglobin (p=0.002) and positively correlated with creatinine (p<0.001). Post-delivery BNP was positively associated with body weight change during pregnancy (p=0.001) and post-delivery creatinine (p=0.010) but negatively associated with body weight loss at delivery (p<0.001) and post-delivery hemoglobin (p=0.004). Even normal pregnancy affects plasma BNP, particularly in the early postpartum period, indicative of cardiac stress. Plasma BNP levels are affected by BMI, body weight changes, creatinine and hemoglobin levels; therefore, these factors should be considered when analysing cardiac function and the physiological implications of BNP levels in pregnant women. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Increased N7-methyldeoxyguanosine DNA adducts after occupational exposure to pesticides and influence of genetic polymorphisms of paraoxonase-1 and glutathione S-transferase M1 and T1.

PubMed

Gómez-Martín, Antonio; Altakroni, Bashar; Lozano-Paniagua, David; Margison, Geoffrey P; de Vocht, Frank; Povey, Andrew C; Hernández, Antonio F

2015-06-01

There are concerns about genetic risks associated with long-term exposure to pesticides as these compounds may damage DNA, resulting in mutations that eventually lead to cancer, neurological, and reproductive adverse health effects. This study assessed DNA damage in intensive agricultural workers exposed to pesticides by determining the levels of N7-methyldeoxyguanosine (N7-MedG), an adduct known to be a robust biomarker of recent exposure to chemical methylating agents. A cohort of 39 plastic greenhouse workers was assessed for changes in lymphocyte DNA N7-MedG levels between low level and high level exposures during the course of a spraying season. The contributions of genetic polymorphisms of the pesticide-metabolizing enzymes paraoxonase-1 (PON1) and the glutathione S-transferases, GSTM1 and GSTT1, on N7-MedG levels and other potential confounders were also assessed. N7-MedG increased in the period of high pesticide exposure as compared to the low exposure period (0.23 and 0.18 µmol N7-MedG/mol dG for the unadjusted and adjusted linear mixed models, P = 0.02 and 0.08, respectively). Significant decreased levels of erythrocyte acetylcholinesterase and plasma cholinesterase were observed in the high versus low exposure period in both the unadjusted (2.85 U/g hemoglobin and 213.13 U/L, respectively) and adjusted linear mixed models (2.99 U/g hemoglobin and 230.77 U/L, respectively), indicating pesticide intake. In intensive agriculture workers, higher pesticide exposure increased DNA alkylation levels, further demonstrating the genotoxicity of pesticides in man. In addition, pesticide-exposed individuals with inherited susceptible metabolic genotypes (particularly, null genotype for GSTM1 and the PON1 192R allele) appear to have an increased risk of genotoxic DNA damage. Environ. Mol. Mutagen. 56:437-445, 2015. © 2014 Wiley Periodicals, Inc. © 2014 Wiley Periodicals, Inc.

High oxygen affinity hemoglobins.

PubMed

Mangin, O

2017-02-01

High oxygen affinity hemoglobins are responsible for rare and heterogeneous autosomic dominant genetic diseases. They cause pure erythrocytosis, sometimes accountable for hyperviscosity and thrombosis, or hemolysis. Differential diagnoses must be first ruled out. The diagnosis is based on the identification of a decreased P50, and their possible characterization by cation exchange-high performance liquid chromatography and capillary electrophoresis. Finally, genetic studies of the responsible globin chain gene will confirm the mutation. The prognosis mainly relies on the P50 decrease rate and on the hemoglobin cooperativity impairment. Disease management should be personalized, and it should primarily depend on smoking cessation and physical activity. Phlebotomy and platelet aggregation inhibitors' prescriptions can be discussed. There is no contraindication to flights, high-altitude conditions, or pregnancy. Nevertheless, blood donation must be prohibited. Copyright © 2016 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.

Blood transfusion reduction with intravenous iron in gynecologic cancer patients receiving chemotherapy.

PubMed

Dangsuwan, Penkae; Manchana, Tarinee

2010-03-01

To compare the incidence of repeated red blood cell (RBC) transfusion in anemic gynecologic cancer patients receiving platinum-based chemotherapy comparing intravenous and oral iron. Forty-four anemic gynecologic cancer patients (hemoglobin level below 10 mg/dl) who required RBC transfusion were stratified and randomized according to baseline hemoglobin levels and chemotherapy regimen. Study group received 200 mg of intravenous iron sucrose and control group received oral ferrous sulphate 600 mg/day. RBC transfusion requirement in the consecutive cycle of chemotherapy was the primary outcome. Quality of life was evaluated by validated Thai version of the Functional Assessment of Cancer Therapy-Anemia (FACT-An). In a total of the 44 patients, there were 22 patients in each group. Five patients (22.7%) in the study group and 14 patients (63.6%) in the control group required RBC transfusion in consecutive cycle of chemotherapy (p=0.01). No significant difference in baseline hemoglobin and hematocrit levels was demonstrated in both groups. Significantly higher mean hemoglobin and hematocrit levels after treatment were reported in the study group (10.0+/-0.8 g/dl and 30.5+/-2.4%) than the control group (9.5+/-0.9 g/dl and 28.4+/-2.7%). No significant change of total FACT-An scores was noted between before and after treatment in both groups. No serious adverse events were reported and there was no significant difference among adverse events between both groups. Intravenous iron is an alternative treatment for anemic gynecologic cancer patients receiving platinum-based chemotherapy and reduces the incidence of RBC transfusion without serious adverse events.

The effect of nandrolone decanoate on bone mineral density, muscle mass, and hemoglobin levels in elderly women with osteoporosis: a double-blind, randomized, placebo-controlled clinical trial.

PubMed

Frisoli, Alberto; Chaves, Paulo H M; Pinheiro, Marcelo Medeiros; Szejnfeld, Vera Lucia

2005-05-01

In a randomized, double-blind, placebo-controlled clinical trial, we evaluated the effect of a 2-year treatment with nandrolone decanoate (ND) on bone mineral density (BMD) of lumbar spine, femoral neck, and trochanter and on vertebral fracture rate, muscle mass, and hemoglobin levels. Sixty-five osteoporotic women older than 70 years were studied. Thirty-two patients received injections of 50 mg ND, and 33 received placebos every 3 weeks. All patients received 500 mg calcium tablets daily. Compared to baseline, ND increased the BMD of the lumbar spine (3.4% +/- 6.0 and 3.7% +/- 7.4; p < .05) and femoral neck (4.1% +/- 7.3 and 4.7% +/- 8.0; p < .05) after 1 and 2 years, respectively. The BMD of trochanter increased significantly only after the first year (4.8% +/- 9.3, p < .05). Compared to the placebo group, the ND group presented with significantly increased BMD of the trochanter and neck. ND significantly reduced incidence of new vertebral fractures (21% vs 43% in the placebo group; p < .05). ND showed a significant statistical increase in lean body mass after the first (6.2% +/- 5.8; p < .01) and second years (11.9% +/- 29.2; p < .01). In addition, a 2-year treatment with ND significantly increased hemoglobin levels compared to baseline (14.3%; p < .01) and placebo (p < .01). ND increased BMD, hemoglobin levels, and muscle mass, and reduced the vertebral fracture rate of elderly osteoporotic women.

Granulocyte-colony stimulating factor administration among hemoglobin S trait donors: A single center experience from the Eastern Mediterranean region.

PubMed

Gereklioglu, Cigdem; Asma, Suheyl; Korur, Aslı; Tepebaşı, Songul; Aytan, Pelin; Yeral, Mahmut; Kozanoglu, Ilknur; Boga, Can; Ozdogu, Hakan

2018-02-01

Assessment of Hemoglobin S trait donors has gained importance together with the increased allogeneic peripheral stem cell transplant activity for sickle cell disease in the regions where the disease is prevalent. Outcomes of Granulocyte-Colony Stimulating Factor (G-CSF) administration are obscure for hemoglobin S trait donors. This study aims at investigating the incidence of hemoglobin S carrier status and outcomes of G-CSF administration among donors who live in Eastern Mediterranean region. The cross-sectional, single-center cohort study was performed with 147 donors between January 2013 and March 2017. Prevalence of hemoglobin S trait was estimated and subjects with or without Hemogobin S trait were compared with regard to stem cell characteristics, early and late clinical outcomes after G-CSF administration. Eleven out of 147 donors (7.48%) were found as hemoglobin S trait. G-CSF administration was successfully completed and yielded good harvesting results in hemoglobin S trait donors. No statistically significant difference was found between groups with regard to early and late side effects, stem cell characteristics. Blood pressures and QTc values were within normal ranges in both groups. Groups were similar with regard to CD34 values. G-CSF seems safe in hemoglobin S trait donors. Their being eligible as donors would increase the chance of the patients for allogeneic stem cell transplantation in high prevalence regions. Further studies are required to reveal the safety profile of G-SCF in hemoglobin S carriers in different regions. © 2017 Wiley Periodicals, Inc.

Genomic organization and evolution of the Atlantic salmon hemoglobin repertoire

PubMed Central

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 the loss of a single hemoglobin gene cluster after the whole genome duplication (WGD) at the base of the teleost radiation but prior to the salmonid-specific WGD, which then produced the duplicated copies seen today. We also propose that the relatively high number of hemoglobin genes as well as the presence of non-Bohr β hemoglobin genes may be due to the dynamic life history of salmon and the diverse environmental conditions that the species encounters. Data deposition: BACs S0155C07 and S0079J05 (fps135): GenBank GQ898924; BACs S0055H05 and S0014B03 (fps1046): GenBank GQ898925 PMID:20923558

Subunit dissociation in fish hemoglobins.

PubMed

Edelstein, S J; McEwen, B; Gibson, Q H

1976-12-10

The tetramer-dimer dissociation equilibria (K 4,2) of several fish hemoglobins have been examined by sedimentation velocity measurements with a scanner-computer system for the ultracentrifuge and by flash photolysis measurements using rapid kinetic methods. Samples studied in detail included hemoglobins from a marine teleost, Brevoortia tyrannus (common name, menhaden); a fresh water teleost, Cyprinus carpio, (common name, carp); and an elasmobranch Prionace glauca (common name, blue shark). For all three species in the CO form at pH 7, in 0.1 M phosphate buffer, sedimentation coefficients of 4.3 S (typical of tetrameric hemoglobin) are observed in the micromolar concentration range. In contrast, mammalian hemoglobins dissociate appreciably to dimers under these conditions. The inability to detect dissociation in three fish hemoglobins at the lowest concentrations examined indicates that K 4,2 must have a value of 10(-8) M or less. In flash photolysis experiments on very dilute solutions in long path length cells, two kinetic components were detected with their proportions varying as expected for an equilibrium between tetramers (the slower component) and dimers (the faster component); values of K 4,2 for the three fish hemoglobins in the range 10(-9) to 10(-8) M were calculated from these data. Thus, the values of K 4,2 for liganded forms of the fish hemoglobins appear to be midway between the value for liganded human hemoglobin (K 4,2 approximately 10(-6) M) and unliganded human hemoglobin (K 4,2 approximately 10(-12) M). This conclusion is supported by measurements on solutions containing guanidine hydrochloride to enhance the degree of dissociation. All three fish hemoglobins are appreciably dissociated at guanidine concentrations of about 0.8 M, which is roughly midway between the guanidine concentrations needed to cause comparable dissociation of liganded human hemoglobin (about 0.4 M) and unliganded human hemoglobin (about 1.6 M). Kinetic measurements on solutions containing guanidine hydrochloride indicated that there are changes in both the absolute rates and the proportions of the fast and slow components, which along with other factors complicated the analysis of the data in terms of dissociation constants. Measurements were also made in solutions containing urea to promote dissociation, but with this agent very high concentrations (about 6 M) were required to give measureable dissociation and the fish hemoglobins were unstable under these conditions, with appreciable loss of absorbance spectra in both the sedimentation and kinetic experiments.

HEMOGLOBIN AND PLASMA PROTEIN PRODUCTION

PubMed Central

Robscheit-Robbins, F. S.; Miller, L. L.; Whipple, G. H.

1946-01-01

Given healthy dogs, fed abundant iron and protein-free or low protein diets, with sustained anemia and hypoproteinemia due to bleeding, we can study the capacity of these animals to produce simultaneousiy new hemoglobin and plasma protein. The reserve stores of blood protein-producing materials in this way are largely depleted, and levels of 6 to 8 gm. per cent for hemoglobin and 4 to 5 gm. per cent for plasma protein can be maintained for considerable periods of time. These dogs are very susceptible to infection and to injury by many poisons. Dogs tire of these diets and loss of appetite terminates many experiments. These incomplete experiments are not recorded in the present paper but give supporting evidence in harmony with those tabulated. Under these conditions (double depletion) the dogs use effectively the proteins listed above—egg, lactalbumin, meat, beef plasma, and digests of various food proteins and hemoglobin. Egg protein at times seems to favor slightly the production of plasma protein when compared with the average response (Tables 1 and 2). Various digests and concentrates compare favorably with good food proteins in the production of new hemoglobin and plasma protein in these doubly depleted dogs. Whole beef plasma by mouth is well utilized and the production of new hemoglobin is, if anything, above the average—certainly plasma protein production is not especially favored. "Modified" beef plasma by vein causes fatal anaphylaxis (Table 4). Hemoglobin digests are well used by mouth to form both hemoglobin and plasma protein. Supplementation by amino acids is recorded. Methionine in one experiment may have been responsible for a better protein output and digest utilization (Table 7). PMID:19871543

Hospitals adopt intensive programs for diabetic patients to avoid high inpatient costs.

PubMed

Conklin, M S

1994-06-01

Just over a year ago, a 24-year-old man walked into a free health screening at Palmyra Medical Centers in Albany, Ga., complaining of weight loss, unending thirst and frequent urination. A quick blood test revealed the man was diabetic, with an alarming hemoglobin A1c level of 20.1. After six months of intervention, the man's hemoglobin dropped to an excellent rating of 7.1 and his physician is now ready to take him off insulin, said Layne Cox, program manager of the Diabetes Treatment Center at Palmyra, a Columbia/HCA hospital. While health fairs of yesterday were used to attract patients into the hospital, today's outreach programs are measured by success stories such as this. The goal now is to keep patients healthy and out of the hospital to reduce costs to managed care plans and health-care providers at risk through capitation contracts.

Improved ethanol production from cheese whey, whey powder, and sugar beet molasses by "Vitreoscilla hemoglobin expressing" Escherichia coli.

PubMed

Akbas, Meltem Yesilcimen; Sar, Taner; Ozcelik, Busra

2014-01-01

This work investigated the improvement of ethanol production by engineered ethanologenic Escherichia coli to express the hemoglobin from the bacterium Vitreoscilla (VHb). Ethanologenic E. coli strain FBR5 and FBR5 transformed with the VHb gene in two constructs (strains TS3 and TS4) were grown in cheese whey (CW) medium at small and large scales, at both high and low aeration, or with whey powder (WP) or sugar beet molasses hydrolysate (SBMH) media at large scale and low aeration. Culture pH, cell growth, VHb levels, and ethanol production were evaluated after 48 h. VHb expression in TS3 and TS4 enhanced their ethanol production in CW (21-419%), in WP (17-362%), or in SBMH (48-118%) media. This work extends the findings that "VHb technology" may be useful for improving the production of ethanol from waste and byproducts of various sources.

Assessment of knowledge level on anaemia among pregnant women in Putrajaya

NASA Astrophysics Data System (ADS)

Adznam, Siti Nur'Hidayah; Sedek, Razalee; Kasim, Zalifah Mohd

2018-04-01

Anaemia during pregnancy is a common problem which affects both the mother's and her child's health. The aim of this study was to determine knowledge level on anaemia among pregnant women in Putrajaya. This study was also been carried out to identify the relationship between knowledge according to socio-demographic and antenatal characteristics. A total of 370 subjects were participated in this study. Subjects comprised of pregnant women who attended four health clinics in Putrajaya to undergo first antenatal visit for the current pregnancy. Socio-demographic information, antenatal characteristics and knowledge related to anaemia were collected using questionnaires. Blood samples were taken to identify hemoglobin level of subjects using Sysmex Hematology Analyzer machine (Sysmex Europe GmbH). The mean age of subjects was 30.2 ± 4.2 years and the mean hemoglobin level was 12.1 ± 4.8 g/dL. The median score for subject's knowledge towards anaemia was 84.2 corresponding to a high level of anaemia knowledge. Result of this study revealed that 55.7% of subjects had high knowledge on anaemia during pregnancy while 28.6% had moderate knowledge followed by 15.7% with low knowledge score. Most subjects correctly answered the general questions on the survey but under the assumption regarding the cause of anaemia. They were also lacking in knowledge regarding the risks of anaemia. Knowledge score was significantly associated with gestational week (p<0.05) and number of children (p<0.01) while there were no significant association with others characteristics. Improvement of anaemia knowledge is the most relevant step to ensure the practice and attitude of subjects towards anaemia are at its optimum level during pregnancy. The results of this study have identified specific areas of health education for pregnant women with regard to anaemia.

Effect of Chronic Blood Transfusion on Biomarkers of Coagulation Activation and Thrombin Generation in Sickle Cell Patients at Risk for Stroke

PubMed Central

Hyacinth, Hyacinth I.; Adams, Robert J.; Greenberg, Charles S.; Voeks, Jenifer H.; Hill, Allyson; Hibbert, Jacqueline M.; Gee, Beatrice E.

2015-01-01

Hypercoagulability in sickle cell disease (SCD) is associated with multiple SCD phenotypes, association with stroke risk has not been well described. We hypothesized that serum levels of biomarkers of coagulation activation correlate with high transcranial Doppler ultrasound velocity and decreases with blood transfusion therapy in SCD patients. Stored serum samples from subjects in the Stroke Prevention in Sickle Cell Anemia (STOP) trial were analyzed using ELISA and protein multiplexing techniques. 40 subjects from each treatment arm (Standard Care [SC] and Transfusion [Tx]) at three time points—baseline, study exit and one year post-trial and 10 each of age matched children with SCD but normal TCD (SNTCD) and with normal hemoglobin (HbAA) were analyzed. At baseline, median vWF, TAT and D-dimer levels were significantly higher among STOP subjects than either HbAA or SNTCD. At study exit, median hemoglobin level was significantly higher while median TCD velocity was significantly lower in Tx compared to SC subjects. Median vWF (409.6 vs. 542.9 μg/ml), TAT (24.8 vs. 40.0 ng/ml) and D-dimer (9.2 vs. 19.1 μg/ml) levels were also significantly lower in the Tx compared to the SC group at study exit. Blood levels of biomarkers coagulation activation/thrombin generation correlated positively with TCD velocity and negatively with number of blood transfusions. Biomarkers of coagulation activation/thrombin generation were significantly elevated in children with SCD, at high risk for stroke. Reduction in levels of these biomarkers correlated with reduction in stroke risk (lower TCD velocity), indicating a possible role for hypercoagulation in SCD associated stroke. PMID:26305570

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

PubMed

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

2016-01-01

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

Microscopic diffusion and hydrodynamic interactions of hemoglobin in red blood cells.

PubMed

Doster, Wolfgang; Longeville, Stéphane

2007-08-15

The cytoplasm of red blood cells is congested with the oxygen storage protein hemoglobin occupying a quarter of the cell volume. The high protein concentration leads to a reduced mobility; the self-diffusion coefficient of hemoglobin in blood cells is six times lower than in dilute solution. This effect is generally assigned to excluded volume effects in crowded media. However, the collective or gradient diffusion coefficient of hemoglobin is only weakly dependent on concentration, suggesting the compensation of osmotic and friction forces. This would exclude hydrodynamic interactions, which are of dynamic origin and do not contribute to the osmotic pressure. Hydrodynamic coupling between protein molecules is dominant at short time- and length scales before direct interactions are fully established. Employing neutron spin-echo-spectroscopy, we study hemoglobin diffusion on a nanosecond timescale and protein displacements on the scale of a few nanometers. A time- and wave-vector dependent diffusion coefficient is found, suggesting the crossover of self- and collective diffusion. Moreover, a wave-vector dependent friction function is derived, which is a characteristic feature of hydrodynamic interactions. The wave-vector and concentration dependence of the long-time self-diffusion coefficient of hemoglobin agree qualitatively with theoretical results on hydrodynamics in hard spheres suspensions. Quantitative agreement requires us to adjust the volume fraction by including part of the hydration shell: Proteins exhibit a larger surface/volume ratio compared to standard colloids of much larger size. It is concluded that hydrodynamic and not direct interactions dominate long-range molecular transport at high concentration.

Validation of NIRS in measuring tissue hemoglobin concentration and oxygen saturation on ex vivo and isolated limb models

NASA Astrophysics Data System (ADS)

Xu, Xiaorong; Zhu, Wen; Padival, Vikram; Xia, Mengna; Cheng, Xuefeng; Bush, Robin; Christenson, Linda; Chan, Tim; Doherty, Tim; Iatridis, Angelo

2003-07-01

Photonify"s tissue spectrometer uses Near-Infrared Spectroscopy for real-time, noninvasive measurement of hemoglobin concentration and oxygen saturation [SO2] of biological tissues. The technology was validated by a series of ex vivo and animal studies. In the ex vivo experiment, a close loop blood circulation system was built, precisely controlling the oxygen saturation and the hemoglobin concentration of a liquid phantom. Photonify"s tissue spectrometer was placed on the surface of the liquid phantom for real time measurement and compared with a gas analyzer, considered the gold standard to measure oxygen saturation and hemoglobin concentration. In the animal experiment, the right hind limb of each dog accepted onto the study was surgically removed. The limb was kept viable by connecting the femoral vein and artery to a blood-primed extracorporeal circuit. Different concentrations of hemoglobin were obtained by adding designated amount of saline solution into the perfusion circuit. Photonify"s tissue spectrometers measured oxygen saturation and hemoglobin concentration at various locations on the limb and compared with gas analyzer results. The test results demonstrated that Photonify"s tissue spectrometers were able to detect the relative changes in tissue oxygen saturation and hemoglobin concentration with a high linear correlation compared to the gas analyzer

Discovery of GBT440, an Orally Bioavailable R-State Stabilizer of Sickle Cell Hemoglobin.

PubMed

Metcalf, Brian; Chuang, Chihyuan; Dufu, Kobina; Patel, Mira P; Silva-Garcia, Abel; Johnson, Carl; Lu, Qing; Partridge, James R; Patskovska, Larysa; Patskovsky, Yury; Almo, Steven C; Jacobson, Matthew P; Hua, Lan; Xu, Qing; Gwaltney, Stephen L; Yee, Calvin; Harris, Jason; Morgan, Bradley P; James, Joyce; Xu, Donghong; Hutchaleelaha, Athiwat; Paulvannan, Kumar; Oksenberg, Donna; Li, Zhe

2017-03-09

We report the discovery of a new potent allosteric effector of sickle cell hemoglobin, GBT440 ( 36 ), that increases the affinity of hemoglobin for oxygen and consequently inhibits its polymerization when subjected to hypoxic conditions. Unlike earlier allosteric activators that bind covalently to hemoglobin in a 2:1 stoichiometry, 36 binds with a 1:1 stoichiometry. Compound 36 is orally bioavailable and partitions highly and favorably into the red blood cell with a RBC/plasma ratio of ∼150. This partitioning onto the target protein is anticipated to allow therapeutic concentrations to be achieved in the red blood cell at low plasma concentrations. GBT440 ( 36 ) is in Phase 3 clinical trials for the treatment of sickle cell disease (NCT03036813).

Neonatal Screening and the Clinical Outcome in Children with Sickle Cell Disease in Central India

PubMed Central

Upadhye, Dipti S.; Jain, Dipty L.; Trivedi, Yogesh L.; Nadkarni, Anita H.; Ghosh, Kanjaksha; Colah, Roshan B.

2016-01-01

Background Sickle cell disease (SCD) is a major health burden in India. The objective of the study was to establish a neonatal screening program and to understand the clinical course of children with SCD in central India. Methods and Findings Pregnant mothers were screened for sickle hemoglobin using the solubility test. Babies were screened by high performance liquid chromatography if the mother was positive for sickle hemoglobin. The diagnosis was confirmed by molecular analysis. They received early prophylactic treatment and vaccination. Of 2134 newborns screened, 104 were sickle homozygous (SS), seven had sickle β-thalassemia (S-β thal) and 978 were sickle heterozygous (AS). The other hemoglobin abnormalities detected included HbS -δβ thalassemia-1, HbSD disease-2, HbE traits-5, β-thalassemia traits-4, alpha chain variants-3 and HbH disease-1.These babies were followed up regularly for hematological and clinical evaluation. Pain, severe anemia requiring blood transfusions and acute febrile illness were the major complications with 59.7, 45.1 and 42.6 cases per 100 person years. Fetal hemoglobin (HbF) levels were inversely associated with vaso-oclussive crisis (VOC) and severe anemia while presence of alpha thalassemia increased the rate of painful events and sepsis. Six early deaths occurred among the SS babies. Conclusion A systematic follow up of this first newborn SCD cohort in central India showed that 47% of babies presented within 1 year of age. In spite of the presence of the Arab-Indian haplotype many babies had severe manifestations. PMID:26785407

Effects of PCBs and PBDEs on thyroid hormone, lymphocyte proliferation, hematology and kidney injury markers in residents of an e-waste dismantling area in Zhejiang, China.

PubMed

Xu, Peiwei; Lou, Xiaoming; Ding, Gangqiang; Shen, Haitao; Wu, Lizhi; Chen, Zhijian; Han, Jianlong; Wang, Xiaofeng

2015-12-01

Polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) are two typical categories of contaminants released from e-waste dismantling environments. In China, the body burdens of PCBs and PBDEs are associated with abnormal thyroid hormones in populations from e-waste dismantling sites, but the results are limited and contradictory. In this study, we measured the serum levels of PCBs and PBDEs and the thyroid hormone free triiodothyronine (FT3), free thyroxine (FT4) and thyroid-stimulating hormone (TSH) in 40 residents in an e-waste dismantling area and in 15 residents in a control area. Additionally, we also measured some lymphocyte proliferation indexes, hematologic parameters and kidney injury markers, including white blood cells, neutrophils, monocytes, lymphocytes, hemoglobin, platelets, serum creatinine and beta 2-microglobulin (β2-MG). The results indicated that the mean level of ΣPCBs in the exposure group was significantly higher than that in the control group (964.39 and 67.98 ng g(-1), p<0.0001), but the mean level of ΣPBDEs in the exposure group was not significantly higher than that in the controls (139.32 vs. 75.74 ng g(-1), p>0.05). We determined that serum levels of FT3, FT4, monocytes and lymphocytes were significantly lower, whereas the levels of neutrophils, hemoglobin, platelets and serum creatinine were significantly higher in the exposed group (p<0.05). The mean level of ΣPCBs was negatively correlated with levels of FT3, FT4, monocytes and lymphocytes (p<0.05) and positively correlated with levels of neutrophils, hemoglobin, serum creatinine and β2-MG (p<0.05). Additionally, the mean level of ΣPBDEs was positively correlated with levels of white blood cells, hemoglobin and platelets (p<0.05). Our data suggest that exposure to an e-waste dismantling environment may increase the body burdens of PCBs and the specific PBDEs congeners in native residents and that the contaminants released from e-waste may contribute to abnormal changes in body levels of thyroid hormone, hematology and kidney injury markers. Copyright © 2015. Published by Elsevier B.V.

The effect of high- and low-glycemic index energy restricted diets on plasma lipid and glucose profiles in type 2 diabetic subjects with varying glycemic control.

PubMed

Heilbronn, Leonie K; Noakes, Manny; Clifton, Peter M

2002-04-01

To determine whether glycemic index (GI) differentially affects improved glucose and lipid profiles observed during weight loss in overweight subjects previously diagnosed with type 2 diabetes with variable glucose tolerance. Twenty-three female and twenty-two male overweight subjects participated in 12 weeks of energy restriction (average BMI 33.2 kg/m2, age 56.7 years, glycated hemoglobin (GHb) 6.7%). After a four-week run-in on a high saturated fat (SFA) diet (1540 kcal/day, 17% SFA), the free-living subjects were randomly assigned to either a high- (75 GI units) or low- (43 GI units) GI diet (1440 kcal/day, 60% carbohydrate, 5% SFA) for eight weeks. Weight, serum lipids, plasma glucose and glycated hemoglobin were measured every four weeks. An oral glucose tolerance test (OGTT) was also performed at baseline, weeks 4 and 12. From the baseline OGTT results subjects were divided into three groups of low, median and high glucose tolerance. At baseline, BMI, age and glycated hemoglobin concentrations were not different between subjects allocated to the high- or low-GI diets. After four weeks, weight loss was 3.6+/-0.3 kg. Fasting glucose (-5.6%), glycated hemoglobin (-2.8%), area under the glucose curve (-13.0%) and triglyceride (-13.8%) concentrations were reduced (p < 0.02). Between weeks 4 and 12 reductions were observed in weight (-4.9%), fasting glucose (-4.6%), area under glucose curve (-10.1%), glycated hemoglobin (-7.2%), triglyceride (-7.5%) and LDL-C (-13.2%) concentrations. Weight loss was not different between low and high-GI diets. However, glycated hemoglobin was reduced twofold more in subjects consuming a low-GI diet as compared to subjects consuming a high-GI diet, but this was not statistically significant. LDL concentrations were also reduced more in subjects with low glucose tolerance on the low-GI diet (p = 0.02). Weight loss produces substantial improvements in glycemic control and lipoprotein metabolism. Lowering the glycemic index of high carbohydrate, low fat diets increases the fall in LDL cholesterol in subjects with type 2 diabetes with low glucose tolerance, but has little effect on glycemic control.

Dependence of erythroid differentiation on cell replication in dimethyl sulfoxide-treated friend leukemia-virus-infected cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wiens, A.W.; McClintock, P.R.; Papaconstantinou, J.

1976-01-01

The dimethyl sulfoxide (Me/sub 2/SO)-mediated induction of hemoglobin synthesis in Friend leukemia cells (a murine erythroblastoid cell line) is coupled with the number of cell replications occurring in the presence of inducer. Varying concentrations of proflavine increase the generation time of these cells from 24 hours to over 50 hours, and in each case the induction of hemoglobin synthesis follows the completion of two cell doublings. Once the induction is initiated, the rate of hemoglobin accumulation is not affected by proflavine. These data indicate that proflavine does not affect the transcription or translation of globin mRNA and that the delaymore » in induction of hemoglobin synthesis is due to its effect on the rate of cellular replication. In experiments using high concentrations of thymidine to block replication, hemoglobin accumulation is prevented only if the cells are blocked prior to 36 hours after Me/sub 2/SO addition. If the cells have completed two generations in the presence of Me/sub 2/SO, there is no effect upon their ability to synthesize hemoglobin even though their growth is arrested. Thus, the inhibition of hemoglobin synthesis by proflavine is not merely the result of a toxic effect on newly subcultured cells but is due to its effect on cellular replication. These experiments confirm that, after addition of Me/sub 2/SO, Friend leukemia cells require more than one complete cell cycle in order to synthesize hemoglobin.« less

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

NASA Astrophysics Data System (ADS)

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

2017-10-01

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

Lower Hemoglobin Concentration Is Associated with Retinal Ischemia and the Severity of Diabetic Retinopathy in Type 2 Diabetes

PubMed Central

Traveset, Alicia; Rubinat, Esther; Ortega, Emilio; Alcubierre, Nuria; Vazquez, Beatriz; Hernández, Marta; Jurjo, Carmen; Espinet, Ramon; Ezpeleta, Juan Antonio; Mauricio, Didac

2016-01-01

Aims. To assess the association of blood oxygen-transport capacity variables with the prevalence of diabetic retinopathy (DR), retinal ischemia, and macular oedema in patients with type 2 diabetes mellitus (T2DM). Methods. Cross-sectional, case-control study (N = 312) with T2DM: 153 individuals with DR and 159 individuals with no DR. Participants were classified according to the severity of DR and the presence of retinal ischemia or macular oedema. Hematological variables were collected by standardized methods. Three logistic models were adjusted to ascertain the association between hematologic variables with the severity of DR and the presence of retinal ischemia or macular oedema. Results. Individuals with severe DR showed significantly lower hemoglobin, hematocrit, and erythrocyte levels compared with those with mild disease and in individuals with retinal ischemia and macular oedema compared with those without these disorders. Hemoglobin was the only factor that showed a significant inverse association with the severity of DR [beta-coefficient = −0.52, P value = 0.003] and retinal ischemia [beta-coefficient = −0.49, P value = 0.001]. Lower erythrocyte level showed a marginally significant association with macular oedema [beta-coefficient = −0.86, P value = 0.055]. Conclusions. In patients with DR, low blood oxygen-transport capacity was associated with more severe DR and the presence of retinal ischemia. Low hemoglobin levels may have a key role in the development and progression of DR. PMID:27200379

Lower Hemoglobin Concentration Is Associated with Retinal Ischemia and the Severity of Diabetic Retinopathy in Type 2 Diabetes.

PubMed

Traveset, Alicia; Rubinat, Esther; Ortega, Emilio; Alcubierre, Nuria; Vazquez, Beatriz; Hernández, Marta; Jurjo, Carmen; Espinet, Ramon; Ezpeleta, Juan Antonio; Mauricio, Didac

2016-01-01

Aims. To assess the association of blood oxygen-transport capacity variables with the prevalence of diabetic retinopathy (DR), retinal ischemia, and macular oedema in patients with type 2 diabetes mellitus (T2DM). Methods. Cross-sectional, case-control study (N = 312) with T2DM: 153 individuals with DR and 159 individuals with no DR. Participants were classified according to the severity of DR and the presence of retinal ischemia or macular oedema. Hematological variables were collected by standardized methods. Three logistic models were adjusted to ascertain the association between hematologic variables with the severity of DR and the presence of retinal ischemia or macular oedema. Results. Individuals with severe DR showed significantly lower hemoglobin, hematocrit, and erythrocyte levels compared with those with mild disease and in individuals with retinal ischemia and macular oedema compared with those without these disorders. Hemoglobin was the only factor that showed a significant inverse association with the severity of DR [beta-coefficient = -0.52, P value = 0.003] and retinal ischemia [beta-coefficient = -0.49, P value = 0.001]. Lower erythrocyte level showed a marginally significant association with macular oedema [beta-coefficient = -0.86, P value = 0.055]. Conclusions. In patients with DR, low blood oxygen-transport capacity was associated with more severe DR and the presence of retinal ischemia. Low hemoglobin levels may have a key role in the development and progression of DR.

Actual 5-Year Nutritional Outcomes of Patients with Gastric Cancer.

PubMed

Kim, Ki Hyun; Park, Dong Jin; Park, Young Suk; Ahn, Sang Hoon; Park, Do Joong; Kim, Hyung Ho

2017-06-01

In this study, we aimed to evaluate the rarely reported long-term nutritional results of patients with gastric cancer after curative gastrectomy. We retrospectively reviewed the prospectively collected medical records of 658 patients who underwent radical gastrectomy with curative intent for gastric cancer from January 2008 to December 2009 and had no recurrences. All patients were followed for 5 years. Nutritional statuses were assessed using measurements of body weight, serum hemoglobin, total lymphocyte count (TLC), protein, albumin, cholesterol, and nutritional risk index (NRI). Patients who underwent total gastrectomy had lower body weights, hemoglobin, protein, albumin, and cholesterol levels. TLC and NRI valued after the first postoperative year (P<0.05), and lower hemoglobin and NRI valued during the fifth postoperative year than patients who underwent distal gastrectomy (P<0.05). Patients who received adjuvant chemotherapy after gastrectomy had lower hemoglobin, protein, albumin, and cholesterol levels. TLC and NRI valued during the first postoperative year, than those who underwent gastrectomy only (P<0.05). Regarding post-distal gastrectomy reconstruction, those who underwent Roux-en-Y had lower cholesterol levels than did those who underwent Billroth-I and Billroth-II reconstruction at the first and fifth years after gastrectomy, respectively (P<0.05). Patients undergoing total or distal gastrectomy with Roux-en-Y anastomosis or adjuvant chemotherapy after surgery should be monitored carefully for malnutrition during the first postoperative year, and patients undergoing total gastrectomy should be monitored for malnutrition and anemia for 5 years.

Efficient synthesis of molecularly imprinted polymers with bio-recognition sites for the selective separation of bovine hemoglobin.

PubMed

Zhang, Zulei; Li, Lei

2018-06-01

We developed a facile approach to the construction of bio-recognition sites in silica nanoparticles for efficient separation of bovine hemoglobin based on amino-functionalized silica nanoparticles grafting by 3-aminopropyltriethoxylsilane providing hydrogen bonds with bovine hemoglobin through surface molecularly imprinting technology. The resulting amino-functionalized silica surface molecularly imprinted polymers were characterized using scanning electron microscope, transmission electronic microscopy, Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, and thermogravimetric analysis. Results showed that the as-synthesized imprinted polymers exhibited spherical morphology and favorable thermal stability. The binding adsorption experiments showed that the imprinted polymers can reach equilibrium within 1 h. The Langmuir isotherm and pseudo-second-order kinetic model fitted the adsorption data well. Meanwhile, the imprinted polymers possessed a maximum binding capacity up to 90.3 mg/g and highly selectivity for the recognition of bovine hemoglobin. Moreover, such high binding capacity and selectivity retained after eight cycles, indicating the good stability and reusability of the imprinted polymers. Finally, successful application in the selective recognition of bovine hemoglobin from a real bovine blood sample indicated that the imprinted polymers displayed great potentials in efficient purification and separation of target proteins. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Mild splenic sequestration crises in sickle-hemoglobin C disease.

PubMed

Andrews, J; Buchanan, G R

1984-06-01

Acute splenic sequestration crisis ( ASSC ), a common complication in homozygous sickle cell anemia, has been described infrequently in sickle-hemoglobin C (SC) disease in the absence of high altitude exposure. In this report, we describe three children with hemoglobin SC disease who developed episodes of ASSC that were milder than those generally described in sickle cell anemia. In one patient, an antecedent triggering event was not recognized. The other two children may have had a predisposing cause for massive intrasplenic sickling in that one had an associated mononucleosis syndrome and the other an episode of hypovolemic shock following severe epistaxis. ASSC may occur in patients with SC disease and does not necessarily require a hypoxic trigger associated with high altitudes.

Toxicological evaluations of Stigma maydis (corn silk) aqueous extract on hematological and lipid parameters in Wistar rats.

PubMed

Saheed, Sabiu; Oladipipo, Ajani E; Abdulazeez, Abubakar A; Olarewaju, Sulyman A; Ismaila, Nurain O; Emmanuel, Irondi A; Fatimah, Quadri D; Aisha, Abubakar Y

2015-01-01

Despite the acclaimed phytotherapeutic attributes of Stigma maydis in folkloric medicine, there is paucity of information on its toxicity profile on hematological and lipid parameters. The toxicological effect of aqueous extract of corn silk at 100, 200 and 400 mg/kg body weight on hematological indices in Wistar rats were evaluated progressively at 24 h after 1, 7, 14, 21 and 28 days. Lipid parameters were also analyzed at the end of the experimental period. We observed that the extract did not exhibit any significant ( p  > 0.05) effect on red blood cells, hematocrit, hemoglobin, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, and mean platelet volume at all the tested doses. The study however showed a significant increase in the serum levels of white blood cell, platelet, lymphocytes, high-density lipoprotein cholesterol; as well as feeding pattern in the animals, while the concentrations of total cholesterol, low-density lipoprotein cholesterol, and artherogenic index value were significantly lowered. These findings are suggestive of non-hematotoxic potential of the extract. Overall, the effect exhibited by corn silk extract in this study proved that, it is unlikely to be hematotoxic and could be a good candidature in the management of coronary heart diseases if consumed at the doses investigated.

Some blood chemistry values for five Chesapeake Bay area fishes

USGS Publications Warehouse

Hunn, J.B.; Robinson, P.F.

1966-01-01

Blood samples from gizzard shad,largemouth bass, white perch, pumpkinseed, and toadfish were analyzed for hemoglobin, total plasma protein, total plasma cholesterol, and ion concentrations of plasma sodium, potassium, and chloride. The hemoglobin concentration and total plasma cholesterol found in a given species seem to have positive correlation with the customary activity level of that species. The plasma ionic concentrations in general agree with those found by other authors.

Data bank of optical properties of biological tissue and blood in the visible and near infrared spectral region

NASA Astrophysics Data System (ADS)

Khairullina, Alphiya Y.; Bui, Lilia; Oleinik, Tatiana V.; Artishevsky, Nelli; Prigoun, Natalia; Sevkovsky, Jakov; Mokhort, Tatiana

1996-12-01

The data bank contains optical, ordinary biochemical and biophysical information on 120 venous blood samples of donors, healthy persons, patients with high pathology, 60 tissue samples. The optical parameters include diffuse reflection R((lambda) ) and transmission T((lambda) ) coefficients for optically thick layers, the absorption K((lambda) ) and extinction (epsilon) ((lambda) ) spectra, oxygenation degree CO2, parameter p determined by sizes and shapes of cells and their aggregates, refractive index of a disperse phase relative to surrounding media, and cooperative effects at high relative concentration. The peculiarities in absorption K((lambda) spectra are connected with different pathologies. It is shown from K((lambda) ) that the grade of pathology connected with the concentration of hemoglobin and mithohondrion together with oxygenation degree of blood and tissues, with the pathological hemoglobin's forms and its decomposition products of different levels. Parameter p is an important diagnostic parameter. We consider that it is necessary to include the oxygenation degree and erythrocyte's aggregation parameter to extend the range of common diagnostic parameters of blood by the first rota.

Blood lead: Its effect on trace element levels and iron structure in hemoglobin

NASA Astrophysics Data System (ADS)

Jin, C.; Li, Y.; Li, Y. L.; Zou, Y.; Zhang, G. L.; Normura, M.; Zhu, G. Y.

2008-08-01

Lead is a ubiquitous environmental pollutant that induce a broad range of physiological and biochemical dysfunctions. The purpose of this study was to investigate its effects on trace elements and the iron structure in hemoglobin. Blood samples were collected from rats that had been exposed to lead. The concentration of trace elements in whole blood and blood plasma was determined by ICP-MS and the results indicate that lead exists mainly in the red blood cells and only about 1-3% in the blood plasma. Following lead exposure, the concentrations of zinc and iron in blood decrease, as does the hemoglobin level. This indicates that the heme biosynthetic pathway is inhibited by lead toxicity and that lead poisoning-associated anemia occurs. The selenium concentration also decreases after lead exposure, which may lead to an increased rate of free radical production. The effect of lead in the blood on iron structure in hemoglobin was determined by EXAFS. After lead exposure, the Fe-O bond length increases by about 0.07 Å and the Fe-Np bond length slightly increases, but the Fe-N ɛ bond length remains unchanged. This indicates that the blood content of Hb increases, but that the content of HbO 2 decreases.

Direct estimation of evoked hemoglobin changes by multimodality fusion imaging

PubMed Central

Huppert, Theodore J.; Diamond, Solomon G.; Boas, David A.

2009-01-01

In the last two decades, both diffuse optical tomography (DOT) and blood oxygen level dependent (BOLD)-based functional magnetic resonance imaging (fMRI) methods have been developed as noninvasive tools for imaging evoked cerebral hemodynamic changes in studies of brain activity. Although these two technologies measure functional contrast from similar physiological sources, i.e., changes in hemoglobin levels, these two modalities are based on distinct physical and biophysical principles leading to both limitations and strengths to each method. In this work, we describe a unified linear model to combine the complimentary spatial, temporal, and spectroscopic resolutions of concurrently measured optical tomography and fMRI signals. Using numerical simulations, we demonstrate that concurrent optical and BOLD measurements can be used to create cross-calibrated estimates of absolute micromolar deoxyhemoglobin changes. We apply this new analysis tool to experimental data acquired simultaneously with both DOT and BOLD imaging during a motor task, demonstrate the ability to more robustly estimate hemoglobin changes in comparison to DOT alone, and show how this approach can provide cross-calibrated estimates of hemoglobin changes. Using this multimodal method, we estimate the calibration of the 3 tesla BOLD signal to be −0.55% ± 0.40% signal change per micromolar change of deoxyhemoglobin. PMID:19021411

Monitoring exposure to acrylonitrile using adducts with N-terminal valine in hemoglobin.

PubMed

Osterman-Golkar, S M; MacNeela, J P; Turner, M J; Walker, V E; Swenberg, J A; Sumner, S J; Youtsey, N; Fennell, T R

1994-12-01

Human exposure to acrylonitrile (ACN), a carcinogen in rats, may occur in industrial settings, through waste water and tobacco smoke. ACN is an electrophilic compound and binds covalently to nucleophilic sites in macromolecules. Measurements of adducts with hemoglobin could be utilized for improved exposure assessments. In this study, a method for quantification of N-(2-cyanoethyl)valine (CEVal), the product of reaction of ACN with N-terminal valine in hemoglobin has been developed. The method is based on the N-alkyl Edman procedure, which involves derivatization of the globin with pentafluorophenyl isothiocyanate and gas chromatographic-mass spectrometric analysis of the resulting thiohydantoin. An internal standard was prepared by reacting valylglycylglycine with [2H3]ACN, spiked with [14C]ACN to a known sp. act. Levels of CEVal were measured in globin from rats exposed to 3-300 p.p.m. ACN in drinking water for 105 days and from humans (four smokers and four non-smokers). CEVal was detected at all exposure levels in the drinking water study. The relationship between adduct level and water concentration was linear at concentrations of 10 p.p.m. (corresponding to an average daily uptake of c. 0.74 mg ACN/kg body wt during the 65 days prior to sacrifice) and below, with a slope of 37.7 pmol CEVal/g globin/p.p.m. At higher concentrations, adduct levels increased sublinearly, indicating saturation of a metabolic process for elimination of ACN. Comparison of adduct formation with the estimated dose (mg/kg/day) of ACN indicated that at low dose (0-10 p.p.m.) CEVal = 0.508 x ACN dose + 0.048 and at high dose (35-300 p.p.m.) CEVal = 1.142 x ACN dose - 1.098. Globin from the smokers (10-20 cigarettes/day) contained about 90 pmol CEVal/g, whereas the adduct levels in globin from non-smokers were below the detection limit. The analytical sensitivity should be sufficient to allow monitoring of occupationally exposed workers at levels well below the current Occupational Safety and Health Administration standard of 2 p.p.m.

Influence of hemoglobin on non-invasive optical bilirubin sensing

NASA Astrophysics Data System (ADS)

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.

High temperature unfolding of a truncated hemoglobin by molecular dynamics simulation.

PubMed

Sharma, Ravi Datta; Kanwal, Rajnee; Lynn, Andrew M; Singh, Prerna; Pasha, Syed Tazeen; Fatma, Tasneem; Jawaid, Safdar

2013-09-01

Heme containing proteins are associated with peroxidase activity. The proteins like hemoglobin, myoglobins, cytochrome c and micro-peroxidase other than peroxidases have been shown to exhibit weak peroxidase-like activity. This weak peroxidase-like activity in hemoglobin-like molecules is due to heme moiety. We conducted molecular dynamics (MD) studies to decipher the unfolding path of Ba-Glb (a truncated hemoglobin from Bacillus anthracis) and the role of heme moiety to its unfolding path. The similar unfolding path is also observed in vitro by UV/VIS spectroscopy. The data confirmed that the unfolding of Ba-Glb follows a three state process with a meta-stable (intermediate) state between the native and unfolded conformations. The present study is supported by several unfolding parameters like root-mean-square-deviation (RMSD), dictionary of protein secondary structure (DSSP), and free energy landscape. Understanding the structure of hemoglobin like proteins in unicellular dreaded pathogens like B. anthracis will pave way for newer drug discovery targets and in the disease management of anthrax.

Senicapoc (ICA-17043): a potential therapy for the prevention and treatment of hemolysis-associated complications in sickle cell anemia.

PubMed

Ataga, Kenneth I; Stocker, Jonathan

2009-02-01

Sickle cell disease (SCD) is characterized by hemolytic as well as vaso-occlusive complications. The development of treatments for this inherited disease is based on an understanding of its pathophysiology. Polymerization of sickle hemoglobin is dependent on several independent factors, including the intracellular hemoglobin concentration. The hydration state (and intracellular hemoglobin concentration) of the sickle erythrocyte depends on the loss of solute and osmotically obliged water through specific pathways. Senicapoc (also known as ICA-17043) is a potent blocker of the Gardos channel, a calcium-activated potassium channel of intermediate conductance, in the red blood cell. Preclinical studies and studies in transgenic models of SCD show that inhibition of potassium efflux through the Gardos channel is associated with an increased hemoglobin level, decreased dense cells and decreased hemolysis. Senicapoc is well tolerated when administered to SCD patients and produces dose-dependent increases in hemoglobin and decreases in markers of hemolysis. Despite the lack of a reduction in the frequency of pain episodes, the increasing recognition that hemolysis contributes to the development of several SCD-related complications suggests that by decreasing hemolysis, senicapoc may yet prove to be beneficial in this disease.

Second Trimester Maternal Serum Screening for Fetal Down Syndrome: as a Screening Test for Hemoglobin Bart's Disease: A Prospective Population-based Study.

PubMed

Wanapirak, Chanane; Piyamomgkol, Wirawit; Sirichotiyakul, Supatra; Tongprasert, Fuanglada; Srisupundit, Kasemsri; Luewan, Suchaya; Traisrisilp, Kuntharee; Jatavan, Phudit; Tongsong, Theera

2018-06-21

To determine the effectiveness of second-trimester maternal serum screening (MSS) for Down syndrome as a screening test for fetal hemoglobin (Hb) Bart's disease among an unselected population. A secondary analysis of a large prospective database (20,254 pregnancies) was conducted to compare the levels of MSS, alpha-fetoprotein (AFP), free beta-human chorionic gonadotropin (hCG) and unconjugated estriol (uE3) between pregnancies with Hb Bart's disease and unaffected pregnancies. The median AFP levels were much higher among affected fetuses, (1.96 vs. 1.12 multiple of the median (MoM); p<0.001), yielding a sensitivity of 81.6% and specificity of 86.4%. Thus, AFP measurement is effective in predicting fetal Hb Bart's disease among an unselected population when using a cut-off value of 1.5 MoM. The serum free b-hCG levels were slightly, but significantly, higher in the affected pregnancies, while the serum uE3 levels were minimally, but significantly, lower among the affected pregnancies. Second trimester maternal serum AFP levels were significantly elevated in cases of fetal Hb Bart's disease. Pregnancies with unexplained elevated serum AFP levels in areas of high prevalence of Hb Bart's disease should always undergo a detailed ultrasound examination to detect any early signs of fetal anemia before development of hydrops fetalis. This article is protected by copyright. All rights reserved.

Promotion of spinosad biosynthesis by chromosomal integration of the Vitreoscilla hemoglobin gene in Saccharopolyspora spinosa.

PubMed

Luo, Yushuang; Kou, Xiaoxiao; Ding, Xuezhi; Hu, Shengbiao; Tang, Ying; Li, Wenping; Huang, Fan; Yang, Qi; Chen, Hanna; Xia, Liqiu

2012-02-01

To promote spinosad biosynthesis by improving the limited oxygen supply during high-density fermentation of Saccharopolyspora spinosa, the open reading frame of the Vitreoscilla hemoglobin gene was placed under the control of the promoter for the erythromycin resistance gene by splicing using overlapping extension PCR. This was cloned into the integrating vector pSET152, yielding the Vitreoscilla hemoglobin gene expression plasmid pSET152EVHB. This was then introduced into S. spinosa SP06081 by conjugal transfer, and integrated into the chromosome by site-specific recombination at the integration site ΦC31 on pSET152EVHB. The resultant conjugant, S. spinosa S078-1101, was genetically stable. The integration was further confirmed by PCR and Southern blotting analysis. A carbon monoxide differential spectrum assay showed that active Vitreoscilla hemoglobin was successfully expressed in S. spinosa S078-1101. Fermentation results revealed that expression of the Vitreoscilla hemoglobin gene significantly promoted spinosad biosynthesis under normal oxygen and moderately oxygen-limiting conditions (P<0.01). These findings demonstrate that integrating expression of the Vitreoscilla hemoglobin gene improves oxygen uptake and is an effective means for the genetic improvement of S. spinosa fermentation.

Polyphenolic compounds appear to limit the nutritional benefit of biofortified higher iron black bean (Phaseolus vulgaris L.)

PubMed Central

2014-01-01

Background Our objective was to determine if a biofortified variety of black bean can provide more bioavailable-iron (Fe) than a standard variety. Two lines of black beans (Phaseolus-vulgaris L.), a standard (DOR500; 59μg Fe/g) and biofortified (MIB465; 88μg Fe/g) were used. The DOR500 is a common commercial variety, and the MIB465 is a line developed for higher-Fe content. Given the high prevalence of Fe-deficiency anemia worldwide, it is important to determine if Fe-biofortified black beans can provide more absorbable-Fe. Methods Black bean based diets were formulated to meet the nutrient requirements for the broiler (Gallus-gallus) except for Fe (dietary Fe-concentrations were 39.4±0.2 and 52.9±0.9 mg/kg diet, standard vs. biofortified, respectively). Birds (n=14) were fed the diets for 6-weeks. Hemoglobin-(Hb), liver-ferritin and Fe-related transporter/enzyme gene-expression were measured. Hemoglobin-maintenance-efficiency and total-body-Hb-Fe values were used to estimate Fe-bioavailability. Results Hemoglobin-maintenance-efficiency values were higher (P<0.05) in the group consuming the standard-Fe beans on days 14, 21 and 28; indicating a compensatory response to lower dietary-Fe. Final total-Hb-Fe body content was higher in the biofortified vs. the standard group (26.6±0.9 and 24.4±0.8 mg, respectively; P<0.05). There were no differences in liver-ferritin or in expression of DMT-1, Dcyt-B, and ferroportin. In-vitro Fe-bioavailability assessment indicated very low Fe-bioavailability from both diets and between the two bean varieties (P>0.05). Such extremely-low in-vitro Fe-bioavailability measurement is indicative of the presence of high levels of polyphenolic-compounds that may inhibit Fe-absorption. High levels of these compounds would be expected in the black bean seed-coats. Conclusions The parameters of Fe-status measured in this study indicate that only a minor increase in absorbable-Fe was achieved with the higher-Fe beans. The results also raise the possibility that breeding for increased Fe-concentration elevated the levels of polyphenolic-compounds that can reduce bean Fe-bioavailability, although the higher levels of polyphenolics in the higher-Fe beans may simply be coincidental or an environmental effect. Regardless, Fe-biofortified beans remain a promising vehicle for increasing intakes of bioavailable-Fe in human populations that consume high levels of these beans as a dietary staple, and the bean polyphenol profile must be further evaluated and modified if possible in order to improve the nutritional quality of higher-Fe beans. PMID:24669764

Low modulus biomimetic microgel particles with high loading of hemoglobin.

PubMed

Chen, Kai; Merkel, Timothy J; Pandya, Ashish; Napier, Mary E; Luft, J Christopher; Daniel, Will; Sheiko, Sergei; DeSimone, Joseph M

2012-09-10

We synthesized extremely deformable red blood cell-like microgel particles and loaded them with bovine hemoglobin (Hb) to potentiate oxygen transport. With similar shape and size as red blood cells (RBCs), the particles were fabricated using the PRINT (particle replication in nonwetting templates) technique. Low cross-linking of the hydrogel resulted in very low mesh density for these particles, allowing passive diffusion of hemoglobin throughout the particles. Hb was secured in the particles through covalent conjugation of the lysine groups of Hb to carboxyl groups in the particles via EDC/NHS coupling. Confocal microscopy of particles bound to fluorescent dye-labeled Hb confirmed the uniform distribution of Hb throughout the particle interior, as opposed to the surface conjugation only. High loading ratios, up to 5 times the amount of Hb to polymer by weight, were obtained without a significant effect on particle stability and shape, though particle diameter decreased slightly with Hb conjugation. Analysis of the protein by circular dichroism (CD) spectroscopy showed that the secondary structure of Hb was unperturbed by conjugation to the particles. Methemoglobin in the particles could be maintained at a low level and the loaded Hb could still bind oxygen, as studied by UV-vis spectroscopy. Hb-loaded particles with moderate loading ratios demonstrated excellent deformability in microfluidic devices, easily deforming to pass through restricted pores half as wide as the diameter of the particles. The suspension of concentrated particles with a Hb concentration of 5.2 g/dL showed comparable viscosity to that of mouse blood, and the particles remained intact even after being sheared at a constant high rate (1000 1/s) for 10 min. Armed with the ability to control size, shape, deformability, and loading of Hb into RBC mimics, we will discuss the implications for artificial blood.

Low Modulus Biomimetic Microgel Particles with High Loading of Hemoglobin

PubMed Central

Chen, Kai; Merkel, Timothy J.; Pandya, Ashish; Napier, Mary E.; Luft, J. Christopher; Daniel, Will; Sheiko, Sergei

2012-01-01

We synthesized extremely deformable red blood cell-like microgel particles and loaded them with bovine hemoglobin (Hb) to potentiate oxygen transport. With similar shape and size as red blood cells (RBCs), the particles were fabricated using the PRINT® (Particle Replication In Non-wetting Templates) technique. Low crosslinking of the hydrogel resulted in very low mesh density for these particles, allowing passive diffusion of hemoglobin throughout the particles. Hb was secured in the particles through covalent conjugation of the lysine groups of Hb to carboxyl groups in the particles via EDC/NHS coupling. Confocal microscopy of particles bound to fluorescent dye-labeled Hb confirmed the uniform distribution of Hb throughout the particle interior, as opposed to the surface conjugation only. High loading ratios, up to 5 times the amount of Hb to polymer by weight, were obtained, without a significant effect on particle stability, shape, though particle diameter decreased slightly with Hb conjugation. Analysis of the protein by circular dichroism (CD) spectroscopy showed that the secondary structure of Hb was unperturbed by conjugation to the particles. Methemoglobin in the particles could be maintained at a low level and the loaded Hb could still bind oxygen as studied by UV-vis spectroscopy. Hb-loaded particles with moderate loading ratios demonstrated excellent deformability in microfluidic devices, easily deforming to pass through restricted pores half as wide as the diameter of the particles. The suspension of concentrated particles with Hb concentration of 5.2 g/dL showed comparable viscosity to that of mouse blood, and the particles remained intact even after being sheared at a constant high rate (1,000 1/s) for 10 min. Armed with the ability to control size, shape, deformability, and loading of Hb into RBC mimics, we will discuss the implications for artificial blood. PMID:22852860

Blood transfusion in pediatric cardiac surgery.

PubMed

Durandy, Yves

2010-11-01

The aim of the study is to measure the volume of homologous blood needed for one pediatric patient during his hospital stay. Over a 4-month period, all the patients operated upon with a blood prime or requiring blood transfusion during their hospital stay were included in this study.The cardiopulmonary bypass protocol associates a miniaturized bypass circuit, vacuum-assisted venous drainage, and microplegia. The volume of each blood product opened is known and the volume of blood product remaining, following the last transfusion, is measured. Data collected areas follows: patient weight; hemoglobin level before surgery,during bypass, and in intensive care after the last transfusion;time to extubation; and degree of inotropic support.Forty-six patients weighing 5.1 1.5 kg were included in this study. Cardiopulmonary bypass priming volume was 100 mL for patients up to 3.5 kg, 120 mL for patients between 3.6 and 7.5 kg, and 160 mL for patients between 7.6 and 8.6 kg. The volume of blood transfusion was 271 112 mL, hemoglobin level before surgery was 10.3 1.7 g/dL, hemoglobin level during surgery was 11.0 1.5 g/dL, and hemoglobin level after the last transfusion was 12.3 2.4 g/dL. Time to extubation was 12 3.3 h, and inotropic support was enoximone in 37 patients,whereas 6 patients needed enoximone and epinephrine.No patient needed reexploration for bleeding and one patient received a platelet transfusion.The mean blood transfusion volume was equivalent to 60% of the patient’s total blood volume (estimated to be 80 mL/kg).

Institution of basal-bolus therapy at diagnosis for children with type 1 diabetes mellitus.

PubMed

Adhikari, Soumya; Adams-Huet, Beverley; Wang, Yu-Chi A; Marks, James F; White, Perrin C

2009-04-01

We studied whether the institution of basal-bolus therapy immediately after diagnosis improved glycemic control in the first year after diagnosis for children with newly diagnosed type 1 diabetes mellitus. We reviewed the charts of 459 children > or =6 years of age who were diagnosed as having type 1 diabetes between July 1, 2002, and June 30, 2006 (212 treated with basal-bolus therapy and 247 treated with a more-conventional neutral protamine Hagedorn regimen). We abstracted data obtained at diagnosis and at quarterly clinic visits and compared groups by using repeated-measures, mixed-linear model analysis. We also reviewed the records of 198 children with preexisting type 1 diabetes mellitus of >1-year duration who changed from the neutral protamine Hagedorn regimen to a basal-bolus regimen during the review period. Glargine-treated subjects with newly diagnosed diabetes had lower hemoglobin A1c levels at 3, 6, 9, and 12 months after diagnosis than did neutral protamine Hagedorn-treated subjects (average hemoglobin A1c levels of 7.05% with glargine and 7.63% with neutral protamine Hagedorn, estimated across months 3, 6, 9, and 12, according to repeated-measures models adjusted for age at diagnosis and baseline hemoglobin A1c levels; treatment difference: 0.58%). Children with long-standing diabetes had no clinically important changes in their hemoglobin A1c levels in the first year after changing regimens. The institution of basal-bolus therapy with insulin glargine at the time of diagnosis of type 1 diabetes was associated with improved glycemic control, in comparison with more-conventional neutral protamine Hagedorn regimens, during the first year after diagnosis.

Hemoglobin Cleavage Site-Specificity of the Plasmodium falciparum Cysteine Proteases Falcipain-2 and Falcipain-3

PubMed Central

Subramanian, Shoba; Hardt, Markus; Choe, Youngchool; Niles, Richard K.; Johansen, Eric B.; Legac, Jennifer; Gut, Jiri; Kerr, Iain D.; Craik, Charles S.; Rosenthal, Philip J.

2009-01-01

The Plasmodium falciparum cysteine proteases falcipain-2 and falcipain-3 degrade host hemoglobin to provide free amino acids for parasite protein synthesis. Hemoglobin hydrolysis has been described as an ordered process initiated by aspartic proteases, but cysteine protease inhibitors completely block the process, suggesting that cysteine proteases can also initiate hemoglobin hydrolysis. To characterize the specific roles of falcipains, we used three approaches. First, using random P1 – P4 amino acid substrate libraries, falcipain-2 and falcipain-3 demonstrated strong preference for cleavage sites with Leu at the P2 position. Second, with overlapping peptides spanning α and β globin and proteolysis-dependent 18O labeling, hydrolysis was seen at many cleavage sites. Third, with intact hemoglobin, numerous cleavage products were identified. Our results suggest that hemoglobin hydrolysis by malaria parasites is not a highly ordered process, but rather proceeds with rapid cleavage by falcipains at multiple sites. However, falcipain-2 and falcipain-3 show strong specificity for P2 Leu in small peptide substrates, in agreement with the specificity in optimized small molecule inhibitors that was identified previously. These results are consistent with a principal role of falcipain-2 and falcipain-3 in the hydrolysis of hemoglobin by P. falciparum and with the possibility of developing small molecule inhibitors with optimized specificity as antimalarial agents. PMID:19357776

Associations between comorbid anxiety, diabetes control, and overall medical burden in patients with serious mental illness and diabetes.

PubMed

Bajor, Laura A; Gunzler, Douglas; Einstadter, Douglas; Thomas, Charles; McCormick, Richard; Perzynski, Adam T; Kanuch, Stephanie W; Cassidy, Kristin A; Dawson, Neal V; Sajatovic, Martha

2015-01-01

While previous work has demonstrated elevation of both comorbid anxiety disorders and diabetes mellitus type II in individuals with serious mental illness, little is known regarding the impact of comorbid anxiety on diabetes mellitus type II outcomes in serious mental illness populations. We analyzed baseline data from patients with serious mental illness and diabetes mellitus type II to examine relationships between comorbid anxiety, glucose control as measured by hemoglobin A1c score, and overall illness burden. Using baseline data from an ongoing prospective treatment study involving 157 individuals with serious mental illness and diabetes mellitus type II, we compared individuals with and without a comorbid anxiety disorder and compared hemoglobin A1c levels between these groups to assess the relationship between anxiety and management of diabetes mellitus type II. We conducted a similar analysis using cumulative number of anxiety diagnoses as a proxy for anxiety load. Finally, we searched for associations between anxiety and overall medical illness burden as measured by Charlson score. Anxiety disorders were seen in 33.1% (N=52) of individuals with serious mental illness and diabetes mellitus type II and were associated with increased severity of depressive symptoms and decreased function. Hemoglobin A1c levels were not significantly different in those with or without anxiety, and having multiple anxiety disorders was not associated with differences in diabetes mellitus type II control. However, depressive symptoms were significantly associated with higher hemoglobin A1c levels. Neither comorbid anxiety nor anxiety load was significantly associated with overall medical burden. One in three people with serious mental illness and diabetes mellitus type II had anxiety. Depressive symptoms were significantly associated with Hb1Ac levels while anxiety symptoms had no relation to hemoglobin A1c; this is consistent with previously published work. More studies are needed to better understand the relationship between depression, anxiety, and health management in people with serious mental illness and diabetes mellitus type II. © The Author(s) 2015.

Simulations and experiments of photon propagation in biological tissue and liquid crystal waveguides

NASA Astrophysics Data System (ADS)

Lines, Collin M.

The development of non-invasive methods to probe human tissue is an ongoing challenge in biomedical optics. In vivo measurements by conventional methods are limited by the mean free path (MFP) of a photon, which is governed by the spatial distribution of chromophores and the absorption and scattering properties of the tissue. As one of the strongest chromophores in human tissues, hemoglobin concentrations in human tissue greatly affect the MFP of photons in visible wavelengths (i.e. bruising). Changes in the concentration of hemoglobin and other chromophores within the tissue (minor trauma causing a contusion, increased bilirubin due to jaundice, etc.) will affect the MFP, leading to a visibly different appearance (color) of the tissue. As color perception is a complex physiological process, these changes are diffcult to quantify by human observation alone. The transport of hemoglobin and its breakdown products in tissue is related to a number of medical conditions that could benefit from a non-invasive method to determine the hemoglobin levels.

Effect of 2,3-diphosphoglycerate on oxygen affinity of blood in sickle cell anemia

PubMed Central

Charache, Samuel; Grisolia, Santiago; Fiedler, Adam J.; Hellegers, Andre E.

1970-01-01

Blood of patients with sickle cell anemia (SS) exhibits decreased affinity for oxygen, although the oxygen affinity of hemoglobin S is the same as that of hemoglobin A. SS red cells contain more 2,3-diphosphoglycerate (DPG) than normal erythrocytes. The oxygen affinity of hemolyzed red cells is decreased by added DPG, and hemolysates prepared from SS red cells do not differ from normal hemolysates in this regard. Reduction of oxygen affinity to the levels found in intact SS red cells required DPG concentrations in excess of those found in most SS patients. The same was true of oxygen affinity of patients with pyruvate kinase deficiency. Other organic phosphates, as well as inorganic ions, are known to alter the oxygen affinity of dilute solutions of hemoglobin. These substances, the state of aggregation of hemoglobin molecules, and cytoarchitectural factors probably play roles in determining oxygen affinity of both normal and SS red cells. PMID:5443181

The relationship between extent of hemoglobin purification and the performance characteristics of a blood-based flocculant

USDA-ARS?s Scientific Manuscript database

Whole blood is a highly complex substance. Hemoglobin, the most abundant blood protein, can function as a flocculant of colloidal clay; most of the other blood components exhibit poor flocculant activity. For the purpose of processing raw whole blood into a flocculant product, the practical value of...

FORMATION OF NITRO MUSK ADDUCTS OF RAINBOW TROUT HEMOGLOBIN FOR POTENTIAL USE AS BIOMARKERS OF EXPOSURE

EPA Science Inventory

The high use of nitro musk xylene (MX) and musk ketone (MK) as fragrances, and their persistence and bioaccumulation potential make them ubiquitous environmental contaminants. The 4-amino-MX (AMX) and 2-amino-MK (AMK) metabolites have been detected in trout fish hemoglobin (Hb) s...

Cation-exchange high-performance liquid chromatography for variant hemoglobins and HbF/A2: What must hematopathologists know about methodology?

PubMed

Sharma, Prashant; Das, Reena

2016-03-26

Cation-exchange high-performance liquid chromatography (CE-HPLC) is a widely used laboratory test to detect variant hemoglobins as well as quantify hemoglobins F and A2 for the diagnosis of thalassemia syndromes. It's versatility, speed, reproducibility and convenience have made CE-HPLC the method of choice to initially screen for hemoglobin disorders. Despite its popularity, several methodological aspects of the technology remain obscure to pathologists and this may have consequences in specific situations. This paper discusses the basic principles of the technique, the initial quality control steps and the interpretation of various controls and variables that are available on the instrument output. Subsequent sections are devoted to methodological considerations that arise during reporting of cases. For instance, common problems of misidentified peaks, totals crossing 100%, causes of total area being above or below acceptable limits and the importance of pre-integration region peaks are dealt with. Ultimately, CE-HPLC remains an investigation, the reporting of which combines in-depth knowledge of the biological basics with more than a working knowledge of the technological aspects of the technique.

Human llamas: adaptation to altitude in subjects with high hemoglobin oxygen affinity.

PubMed Central

Hebbel, R P; Eaton, J W; Kronenberg, R S; Zanjani, E D; Moore, L G; Berger, E M

1978-01-01

To assess the adaptive value of the right-shift of the oxyhemoglobin dissociation curve (decreased affinity for oxygen) observed in humans upon altitude exposure, the short-term physiologic responses to altitude-induced hypoxia were evaluated in two subjects with a high oxygen affinity hemoglobin (Hb Andrew-Minneapolis) and in two of their normal siblings. In striking contrast to normal subjects, at moderately high altitude (3,100 m) the high affinity subjects manifested: (a) lesser increments in resting heart rate; (b) minimal increases in plasma and urinary erythropoietin; (c) no decrement in maximal oxygen consumption; and (d) no thrombocytopenia. There was no difference between subject pairs in 2,3-diphosphoglycerate response to altitude exposure. These results tend to contradict the belief that a decrease in hemoglobin oxygen affinity is of adaptive value to humans at moderate altitudes. Rather, they support the hypothesis that, despite disadvantages at low altitude, a left-shifted oxyhemoglobin dissociation curve may confer a degree of preadaptation to altitude. PMID:29054

[Significance of considering hemoglobin derivatives and acid-base balance in the evaluation of the blood oxygen-transport system].

PubMed

Matiushichev, V B; Shamratova, V G; Krapivko, Iu K

2009-12-01

Factor analysis was used to study the pattern of relationships of a number of hematological parameters in clinically healthy young subjects and in patients with moderate anemia. The level of total hemoglobin and the concentration of red blood cells were ascertained to control blood oxygen-transporting function in not full measure and these might be referred to as basic characteristics only conventionally. To clarify the picture, these criteria should be supplemented by the information on other parameters. It is concluded that the introduction of the ratio of a number of hemoglobin derivatives, blood oxygen regimen and acid-base balance can substantially increase the validity of clinical opinions as to this blood function.

Iron deficiency and anemia: a common problem in female elite soccer players.

PubMed

Landahl, Göran; Adolfsson, Peter; Börjesson, Mats; Mannheimer, Clas; Rödjer, Stig

2005-12-01

The objective of the study was to determine the prevalence of iron deficiency and iron deficiency anemia among elite women soccer players. Hemoglobin, serum iron, serum total iron binding capacity, and ferritin were determined in 28 female soccer players called up for the national team. Of the investigated female soccer players, 57% had iron deficiency and 29% iron deficiency anemia 6 months before the FIFA Women's World Cup. It is concluded that iron deficiency and iron deficiency anemia is common in female soccer players at the top international level. Some might suffer from relative anemia and measurement of hemoglobin alone is not sufficient to reveal relative anemia. Regular monitoring of hemoglobin concentration and iron status is necessary to institute iron supplementation when indicated.

The prevalence of abnormal leukocyte count, and its predisposing factors, in patients with sickle cell disease in Saudi Arabia.

PubMed

Ahmed, Anwar E; Ali, Yosra Z; Al-Suliman, Ahmad M; Albagshi, Jafar M; Al Salamah, Majid; Elsayid, Mohieldin; Alanazi, Wala R; Ahmed, Rayan A; McClish, Donna K; Al-Jahdali, Hamdan

2017-01-01

High white blood cell (WBC) count is an indicator of sickle cell disease (SCD) severity, however, there are limited studies on WBC counts in Saudi Arabian patients with SCD. The aim of this study was to estimate the prevalence of abnormal leukocyte count (either low or high) and identify factors associated with high WBC counts in a sample of Saudi patients with SCD. A cross-sectional and retrospective chart review study was carried out on 290 SCD patients who were routinely treated at King Fahad Hospital in Hofuf, Saudi Arabia. An interview was conducted to assess clinical presentations, and we reviewed patient charts to collect data on blood test parameters for the previous 6 months. Almost half (131 [45.2%]) of the sample had abnormal leukocyte counts: low WBC counts 15 (5.2%) and high 116 (40%). High WBC counts were associated with shortness of breath ( P =0.022), tiredness ( P =0.039), swelling in hands/feet ( P =0.020), and back pain ( P =0.007). The mean hemoglobin was higher in patients with normal WBC counts ( P =0.024), while the mean hemoglobin S was high in patients with high WBC counts ( P =0.003). After adjustment for potential confounders, predictors of high WBC counts were male gender (adjusted odds ratio [aOR]=3.63) and patients with cough (aOR=2.18), low hemoglobin (aOR=0.76), and low heart rate (aOR=0.97). Abnormal leukocyte count was common: approximately five in ten Saudi SCD patients assessed in this sample. Male gender, cough, low hemoglobin, and low heart rate were associated with high WBC count. Strategies targeting high WBC count could prevent disease complication and thus could be beneficial for SCD patients.

The effect of a nutrition education program on the nutritional knowledge, hemoglobin levels, and nutritional status of Nicaraguan adolescent girls.

PubMed

Moore, Jean Burley; Pawloski, Lisa; Rodriguez, Claudia; Lumbi, Laura; Ailinger, Rita

2009-01-01

The purpose of this study was to examine the effect of a community-based nutrition education program on the nutritional knowledge, hemoglobin levels, and nutritional status of Nicaraguan adolescent girls and the nutritional knowledge of their mothers. Self-care deficit nursing theory was used in this study. This longitudinal study used a mixed quantitative/qualitative design to study the effect of the nutrition education program. The nonprobability sample consisted of 182 adolescent girls and 67 of their mothers. The setting for the study was a community (barrio) in Managua, Nicaragua. INTERVENTION/MEASUREMENT: A team of nurse and nutrition researchers created the nutrition education program designed to improve girls' and mother's nutrition-related self-care operations. Data collection was carried out for 4 years for girls and 2 years for mothers in Managua, Nicaragua, using questionnaires, a HemoCue, and anthropometric measures. The findings of this study were that girls' and mothers' nutritional knowledge scores significantly improved in most cases after participation in the nutrition intervention program. Girls' hemoglobin levels did not significantly improve and their nutritional status findings were mixed. Girls and mothers described what dietary changes girls made and why.

Elliptocytes and tailed poikilocytes correlate with severity of iron-deficiency anemia.

PubMed

Rodgers, M S; Chang, C C; Kass, L

1999-05-01

This study examines the relationships between abnormal RBC morphology, RBC indices measured with an automated hematology analyzer, serum iron studies, and severity of anemia in patients with findings indicative of iron-deficiency anemia. Counts and morphologic classification of 1,000 RBCs from each of 22 patients were performed, and correlations were determined between parameters. The Student t test was used to determine the level of significance for correlations between parameters. Several significant relationships were found. As the percentage of elliptocytes increased, hemoglobin concentration, hematocrit, RBC concentration, and mean corpuscular hemoglobin level decreased (r = .48, .44, .40, and .49, respectively; P < .05). As the percentage of tailed poikilocytes increased, hemoglobin concentration, hematocrit, and RBC concentration decreased (r = .70, .77, and .71, respectively; P < .01) and RBC distribution width increased (r = .73; P < .01). Of significance, serum ferritin levels, long considered the best single indicator of iron deficiency, showed no correlation with the morphologic abnormalities assessed, severity of anemia, or any of the analyzer-generated indices. Our results indicate that microscopic evaluation of RBC morphology remains an important tool for the pathologist to evaluate the severity of anemia in patients with iron deficiency.

[Effects of high-intensity interval training and nutritional education in patients with type 2 diabetes].

PubMed

Mangiamarchi, Pedro; Caniuqueo, Alexis; Ramírez-Campillo, Rodrigo; Cárdenas, Patricio; Morales, Sylvana; Cano-Montoya, Johnattan; Bresciani, Guilherme; Álvarez, Cristian

2017-07-01

High-intensity interval training (HIIT) improves cardiometabolic markers, but its effects on the quality of life of patients with type 2 diabetes (T2D) is not well known. To determine the effects of a 12-week HIIT exercise program on cardiometabolic and quality of life variables of T2D patients. Nine T2D women were assigned to a HIIT + nutritional education (GE) and 10, to a nutritional education alone group (GC). At baseline and after each intervention, anthropometric and body composition parameters using bio-impedance were assessed, and a blood sample was obtained to measure serum lipid levels, blood glucose and glycated hemoglobin. Quality of life was assessed using the SF-12 questionnaire adapted for the Chilean population. There were no significant changes on the lipid profile variables in the GE group, although HDL cholesterol was increased significantly (p < 0.05) in the GC group. Total fat mass was decreased in the GE group from 43.5 ± 1.5 to 41.9 ± 1.5%, p < 0.01. Fasting glucose and glycated hemoglobin decreased in the GE group. There was a significant correlation between the decrease in total fat mass and that of glycated hemoglobin. There were significant increases in quality of life parameters; physical function, physical role, pain, general health, vitality, emotional role, mental health, and social function in the GE but not in the GC group. A 12-week program of HIIT plus nutritional education improves cardiometabolic and quality of life parameters on type 2 diabetics.

Prevalence of β-Thalassemia and hemoglobin E in two migrant populations of Manipur, North East India.

PubMed

Achoubi, Nongthombam; Asghar, Mohammad; Saraswathy, Kallur Nava; Murry, Benrithung

2012-10-01

Hemoglobinopathies are a group of inherited single-gene disorders found commonly in the Mediterranean region, Middle East, Indian subcontinent, Burma, and South East Asia. As many as 229 mutation variants of β-thalassemia are reported in the world, many community/region-specific mutations. Very little on thalassemia has been reported in Manipur, a North Eastern Indian state. Thus, a community genetic approach through population screening can be applied to the people of Manipur and a total of 602 blood samples from unrelated Meitei Brahmins (n=300) and Meitei Muslims (n=302) were screened for abnormal hemoglobins by Naked Eye Single Tube Red Cell Osmotic Fragility Test (NESTROFT). HBA(2) level was estimated by using high-performance liquid chromatography and molecular analysis was done by using PCR. Sequencing was also carried out to confirm the mutations. High frequencies of NESTROFT positive (10%) and NESTROFT doubtful (11%) cases were found among the Meitei Brahmins in comparison to the Meitei Muslims [NESTROFT positive (3.31%) and NESTROFT doubtful (1.33%)]. The allele frequency of HB*E was 0.022 and 0.012 among the Meitei Brahmin and Meitei Muslim, respectively. Sequencing of the β-globin gene confirmed a very rare β-thalassemia [-90 C→T (0.33%)] among the Meitei Brahmins of Manipur. This mutation with hemoglobin E in one of the present population hints the presence of the Mongoloid stock among them, possibly from China. There is a need for further studies on other populations of Manipur and the neighboring North East Indian states using such genetic markers.

Daily use of Sprinkles micronutrient powder for 2 months reduces anemia among children 6 to 36 months of age in the Kyrgyz Republic: a cluster-randomized trial.

PubMed

Lundeen, Elizabeth; Schueth, Tobias; Toktobaev, Nurjan; Zlotkin, Stanley; Hyder, S M Ziauddin; Houser, Robert

2010-09-01

Iron-deficiency anemia is widespread among young children in the Kyrgyz Republic, and there is an urgent need to identify an effective intervention to address this significant public health problem. To test the effectiveness of a 2-month intervention with daily home fortification of complementary food using micronutrient powder (Sprinkles) in reducing anemia among children 6 to 36 months of age in the Kyrgyz Republic. In this cluster-randomized, community-based effectiveness trial conducted in three regions of the Kyrgyz Republic, 24 clusters of children aged 6 to 36 months were randomly assigned to two groups. The intervention group (12 clusters, n = 1,103) received 60 sachets of micronutrient powder (12.5 mg elemental iron), which were taken as one sachet daily for 2 months. The control group (12 clusters, n = 1,090) did not receive micronutrient powder until after the study period. Blood hemoglobin concentration was assessed at the start and end of the intervention. From baseline to follow-up, the mean hemoglobin concentration in the intervention group increased by 7 g/L, whereas it decreased by 2 g/L in the control group (p < .001). The prevalence of anemia (hemoglobin < 110 g/L) in the intervention group decreased from 72% at baseline to 52% at follow-up, whereas it increased from 72% to 75% in the control group (p < .001). Compliance with the intervention was high, with children consuming on average 45 of the 60 sachets given. A course of 60 Sprinkles micronutrient powder sachets taken daily for 2 months is effective in improving hemoglobin levels and reducing the prevalence of anemia among young children in the Kyrgyz Republic.

Can the hemoglobin characteristics of vesicomyid clam species influence their distribution in deep-sea sulfide-rich sediments? A case study in the Angola Basin

NASA Astrophysics Data System (ADS)

Decker, C.; Zorn, N.; Le Bruchec, J.; Caprais, J. C.; Potier, N.; Leize-Wagner, E.; Lallier, F. H.; Olu, K.; Andersen, A. C.

2017-08-01

Vesicomyids live in endosymbiosis with sulfur-oxidizing bacteria and therefore need hydrogen sulfide to survive. They can nevertheless live in a wide range of sulfide and oxygen levels and depths, which may explain the exceptional diversity of this clam family in deep-sea habitats. In the Gulf of Guinea, nine species of vesicomyid clams are known to live in cold-seep areas with pockmarks from 600 to 3200 m deep, as well as in the organic-rich sediments of the Congo deep-sea fan at 5000 m deep. Our previous study showed that two species living in a giant pockmark have different oxygen carriers, suggesting different adaptations to hypoxia. Here, we studied the hemoglobin structure and oxygen affinity in three other species, Calyptogena valdiviae, Elenaconcha guiness and Abyssogena southwardae to determine whether the characteristics of their oxygen carriers contribute to their distribution in sulfide-rich sediments at a regional scale. Documenting pairwise species associations in various proportions, we give a semi-quantitative account of their local distribution and oxygen and sulfide measurements at seven sites. Mass spectrometry showed that each vesicomyid species has four intracellular monomeric hemoglobin molecules of 15-16 kDa, all differing in their molecular mass. As expected, the monomers showed no cooperativity in oxygen binding. Their oxygen affinities were very high (below 1 Torr), but differed significantly. C. valdiviae had the highest affinity and was dominant in the Harp pockmark, the site with the lowest oxygen content (half the value of fully oxygenated water). A. southwardae dominated in the Congo Lobe area, the site with the deepest sulfides. We discuss how hemoglobin may favor an active, vertical distribution of vesicomyids in sulfide-rich sediments.

White Matter Damage Relates to Oxygen Saturation in Children With Sickle Cell Anemia Without Silent Cerebral Infarcts.

PubMed

Kawadler, Jamie M; Kirkham, Fenella J; Clayden, Jonathan D; Hollocks, Matthew J; Seymour, Emma L; Edey, Rosanna; Telfer, Paul; Robins, Andrew; Wilkey, Olu; Barker, Simon; Cox, Tim C S; Clark, Chris A

2015-07-01

Sickle cell anemia is associated with compromised oxygen-carrying capability of hemoglobin and a high incidence of overt and silent stroke. However, in children with no evidence of cerebral infarction, there are changes in brain morphometry relative to healthy controls, which may be related to chronic anemia and oxygen desaturation. A whole-brain tract-based spatial statistics analysis was carried out in 25 children with sickle cell anemia with no evidence of abnormality on T2-weighted magnetic resonance imaging (13 male, age range: 8-18 years) and 14 age- and race-matched controls (7 male, age range: 10-19 years) to determine the extent of white matter injury. The hypotheses that white matter damage is related to daytime peripheral oxygen saturation and steady-state hemoglobin were tested. Fractional anisotropy was found to be significantly lower in patients in the subcortical white matter (corticospinal tract and cerebellum), whereas mean diffusivity and radial diffusivity were higher in patients in widespread areas. There was a significant negative relationship between radial diffusivity and oxygen saturation (P<0.05) in the anterior corpus callosum and a trend-level negative relationship between radial diffusivity and hemoglobin (P<0.1) in the midbody of the corpus callosum. These data show widespread white matter abnormalities in a sample of asymptomatic children with sickle cell anemia, and provides for the first time direct evidence of a relationship between brain microstructure and markers of disease severity (eg, peripheral oxygen saturation and steady-state hemoglobin). This study suggests that diffusion tensor imaging metrics may serve as a biomarker for future trials of reducing hypoxic exposure. © 2015 American Heart Association, Inc.

Evaluation of a next generation direct whole blood enzymatic assay for hemoglobin A1c on the ARCHITECT c8000 chemistry system.

PubMed

Teodoro-Morrison, Tracy; Janssen, Marcel J W; Mols, Jasper; Hendrickx, Ben H E; Velmans, Mathieu H; Lotz, Johannes; Lackner, Karl; Lennartz, Lieselotte; Armbruster, David; Maine, Gregory; Yip, Paul M

2015-01-01

The utility of HbA1c for the diagnosis of type 2 diabetes requires an accurate, precise and robust test measurement system. Currently, immunoassay and HPLC are the most popular methods for HbA1c quantification, noting however the limitations associated with some platforms, such as imprecision or interference from common hemoglobin variants. Abbott Diagnostics has introduced a fully automated direct enzymatic method for the quantification of HbA1c from whole blood on the ARCHITECT chemistry system. Here we completed a method evaluation of the ARCHITECT HbA1c enzymatic assay for imprecision, accuracy, method comparison, interference from hemoglobin variants and specimen stability. This was completed at three independent clinical laboratories in North America and Europe. The total imprecision ranged from 0.5% to 2.2% CV with low and high level control materials. Around the diagnostic cut-off of 48 mmol/mol, the total imprecision was 0.6% CV. Mean bias using reference samples from IFCC and CAP ranged from -1.1 to 1.0 mmol/mol. The enzymatic assay also showed excellent agreement with HPLC methods, with slopes of 1.01 and correlation coefficients ranging from 0.984 to 0.996 compared to Menarini Adams HA-8160, Bio-Rad Variant II and Variant II Turbo instruments. Finally, no significant effect was observed for erythrocyte sedimentation or interference from common hemoglobin variants in patient samples containing heterozygous HbS, HbC, HbD, HbE, and up to 10% HbF. The ARCHITECT enzymatic assay for HbA1c is a robust and fully automated method that meets the performance requirements to support the diagnosis of type 2 diabetes.

Elevated carboxyhemoglobin in a marine mammal, the northern elephant seal

PubMed Central

Tift, Michael S.; Ponganis, Paul J.; Crocker, Daniel E.

2014-01-01

Low concentrations of endogenous carbon monoxide (CO), generated primarily through degradation of heme from heme-proteins, have been shown to maintain physiological function of organs and to exert cytoprotective effects. However, high concentrations of carboxyhemoglobin (COHb), formed by CO binding to hemoglobin, potentially prevent adequate O2 delivery to tissues by lowering arterial O2 content. Elevated heme-protein concentrations, as found in marine mammals, are likely associated with greater heme degradation, more endogenous CO production and, consequently, elevated COHb concentrations. Therefore, we measured COHb in elephant seals, a species with large blood volumes and elevated hemoglobin and myoglobin concentrations. The levels of COHb were positively related to the total hemoglobin concentration. The maximum COHb value was 10.4% of total hemoglobin concentration. The mean (±s.e.m.) value in adult seals was 8.7±0.3% (N=6), while juveniles and pups (with lower heme-protein contents) had lower mean COHb values of 7.6±0.2% and 7.1±0.3%, respectively (N=9 and N=9, respectively). Serial samples over several hours revealed little to no fluctuation in COHb values. This consistent elevation in COHb suggests that the magnitude and/or rate of heme-protein turnover is much higher than in terrestrial mammals. The maximum COHb values from this study decrease total body O2 stores by 7%, thereby reducing the calculated aerobic dive limit for this species. However, the constant presence of elevated CO in blood may also protect against potential ischemia–reperfusion injury associated with the extreme breath-holds of elephant seals. We suggest the elephant seal represents an ideal model for understanding the potential cytoprotective effects, mechanisms of action and evolutionary adaptation associated with chronically elevated concentrations of endogenously produced CO. PMID:24829326

Elevated carboxyhemoglobin in a marine mammal, the northern elephant seal.

PubMed

Tift, Michael S; Ponganis, Paul J; Crocker, Daniel E

2014-05-15

Low concentrations of endogenous carbon monoxide (CO), generated primarily through degradation of heme from heme-proteins, have been shown to maintain physiological function of organs and to exert cytoprotective effects. However, high concentrations of carboxyhemoglobin (COHb), formed by CO binding to hemoglobin, potentially prevent adequate O2 delivery to tissues by lowering arterial O2 content. Elevated heme-protein concentrations, as found in marine mammals, are likely associated with greater heme degradation, more endogenous CO production and, consequently, elevated COHb concentrations. Therefore, we measured COHb in elephant seals, a species with large blood volumes and elevated hemoglobin and myoglobin concentrations. The levels of COHb were positively related to the total hemoglobin concentration. The maximum COHb value was 10.4% of total hemoglobin concentration. The mean (± s.e.m.) value in adult seals was 8.7 ± 0.3% (N=6), while juveniles and pups (with lower heme-protein contents) had lower mean COHb values of 7.6 ± 0.2% and 7.1 ± 0.3%, respectively (N=9 and N=9, respectively). Serial samples over several hours revealed little to no fluctuation in COHb values. This consistent elevation in COHb suggests that the magnitude and/or rate of heme-protein turnover is much higher than in terrestrial mammals. The maximum COHb values from this study decrease total body O2 stores by 7%, thereby reducing the calculated aerobic dive limit for this species. However, the constant presence of elevated CO in blood may also protect against potential ischemia-reperfusion injury associated with the extreme breath-holds of elephant seals. We suggest the elephant seal represents an ideal model for understanding the potential cytoprotective effects, mechanisms of action and evolutionary adaptation associated with chronically elevated concentrations of endogenously produced CO. © 2014. Published by The Company of Biologists Ltd.

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

PubMed

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 (p<0.05). Furthermore, there was a significant inverse correlation between plasma zinc 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.

Effect of short term zinc supplementation on iron status of children with acute diarrhea.

PubMed

Zaka-ur-Rab, Zeeba; Ahmad, Syed Moiz; Naim, Mohammed; Alam, Seema; Adnan, Mohammad

2015-05-01

To study the effect of short term (2 wk) zinc supplementation on hemoglobin and iron status of children with acute diarrhea. This study was a prospective, open label, single arm interventional trial conducted from June 2008 through October 2009 in a teaching hospital of North India. Three to sixty months old children presenting with acute diarrhea participated in the study. Subjects were supplemented with recommended doses of oral zinc gluconate for 2 wk. Changes in levels of hemoglobin, serum iron, total iron binding capacity, and serum ferritin were the main outcome measures. Sixty-two patients completed the study successfully. The prevalence of anemia before and after 2 wk of zinc supplementation remained unchanged. However, a small decline (p > 0.05) was observed in mean hemoglobin (from 8.95 ± 1.4 to 8.73 ± 1.43 g/dL), serum iron (79.56 ± 45.81 to 78.61 ± 44.41 μg/dL) and ferritin (84.77 ± 45.35 to 83.55 ± 44.10 ng/mL) levels. Total iron binding capacity increased from 331.60 ± 109.72 to 341.30 ± 119.90 μg/dL post supplementation (p > 0.05). Even though statistically insignificant, the small change observed in the levels of hemoglobin, and indicators of iron status following short term zinc supplementation might assume significance in some settings in developing countries where children receive short courses of zinc repeatedly for frequent diarrheal episodes.

Real-world utilization of darbepoetin alfa in cancer chemotherapy patients.

PubMed

Pan, Xiaoyun Lucy; Nordstrom, Beth L; MacLachlan, Sharon; Lin, Junji; Xu, Hairong; Sharma, Anjali; Chandler, David; Li, Xiaoyan Shawn

2017-01-01

Objectives To provide an understanding of darbepoetin alfa dose patterns in cancer patients undergoing myelosuppressive chemotherapy starting from 2011. Study design This is a retrospective cohort study using a proprietary outpatient oncology database. Methods Metastatic, solid tumor cancer patients receiving concomitant myelosuppressive chemotherapy and darbepoetin alfa with an associated hemoglobin <10 g/dL during 2011-2015 were identified. The analysis was restricted to the first continuous exposure to chemotherapy agents (maximum allowable gap of 90 days between consecutive exposures) with darbepoetin alfa for each eligible patient. Initial, maintenance, weekly, and cumulative doses of darbepoetin alfa were examined across all darbepoetin alfa users. Subgroup analyses were conducted by chemotherapy type, baseline hemoglobin level, year of chemotherapy, solid tumor type, and initial dosing schedule. Differences in weekly doses across subgroups were evaluated using Wilcoxon rank-sum tests. Results Among 835 eligible patients, over 90% were 50 years or older. Mean chemotherapy course duration was 248 days, and mean duration of darbepoetin alfa treatment was 106 days. The mean weekly darbepoetin alfa dose was 110 µg. Patients received a mean of 4.3 darbepoetin alfa injections in the first chemotherapy course. There were no statistically significant differences (all P values > .05) in weekly dose by chemotherapy type, baseline hemoglobin level, year of chemotherapy, or solid tumor type. Conclusion The average weekly darbepoetin alfa dose among metastatic cancer patients with chemotherapy-induced anemia from this study was 110 µg, which was lower than the labeled dosage for most adults. This estimate did not differ over time, across chemotherapy regimens, baseline hemoglobin levels, or solid tumor types.

Selected terpenes from leaves of Ocimum basilicum L. induce hemoglobin accumulation in human K562 cells.

PubMed

Feriotto, Giordana; Marchetti, Nicola; Costa, Valentina; Torricelli, Piera; Beninati, Simone; Tagliati, Federico; Mischiati, Carlo

2018-06-01

Re-expression of fetal hemoglobin (HbF) was proposed as a possible therapeutic strategy for β-haemoglobinopathies. Although several inducers of HbF were tested in clinical trials, only hydroxyurea (HU) received FDA approval. Despite it produced adequate HbF levels only in half of HU-treated SCD patients, and was ineffective at all in β-thalassemia patients, beneficial effects of this approach suggested to continue in this direction identifying further molecules capable of inducing HbF. We tested the potential of essential oil isolated from Ocimum basilicum L. leaves (ObEO) in inducing hemoglobin biosynthesis. Initially, dose-dependent effect and kinetics of hemoglobin accumulation in K562 cells after treatment with ObEO were evaluated. ObEO induced dose-dependent hemoglobin accumulation superior to hydroxyurea and rapamycin and a strongest γ-globin mRNA expression. Terpenes composition of ObEO was studied by GC-MS. Three main constituents, linalool, eugenol and eucalyptol, represented about 75% of total. A blend of these three terpenes fully replicated the ObEO's biological effect, thus indicating that one of them or all together could be the active ingredients. When terpenes were tested individually, eugenol was the only one inducing stable hemoglobin accumulation, while eucalyptol and linalool produced only a small transient response. However, eugenol potential was strongly enhanced in the presence of eucalyptol and linalool, suggesting a synergistic effect on hemoglobin accumulation. By these results, the discovery of a new inducer and the interesting activity of a blend of major terpenes from ObOE on Hb accumulation could have positive fallouts on β-thalassemia and sickle cells anemia. Copyright © 2018 Elsevier B.V. All rights reserved.

Identification of a Hemolysis Threshold That Increases Plasma and Serum Zinc Concentration.

PubMed

Killilea, David W; Rohner, Fabian; Ghosh, Shibani; Otoo, Gloria E; Smith, Lauren; Siekmann, Jonathan H; King, Janet C

2017-06-01

Background: Plasma or serum zinc concentration (PZC or SZC) is the primary measure of zinc status, but accurate sampling requires controlling for hemolysis to prevent leakage of zinc from erythrocytes. It is not established how much hemolysis can occur without changing PZC/SZC concentrations. Objective: This study determines a guideline for the level of hemolysis that can significantly elevate PZC/SZC. Methods: The effect of hemolysis on PZC/SZC was estimated by using standard hematologic variables and mineral content. The calculated hemolysis threshold was then compared with results from an in vitro study and a population survey. Hemolysis was assessed by hemoglobin and iron concentrations, direct spectrophotometry, and visual assessment of the plasma or serum. Zinc and iron concentrations were determined by inductively coupled plasma spectrometry. Results: A 5% increase in PZC/SZC was calculated to result from the lysis of 1.15% of the erythrocytes in whole blood, corresponding to ∼1 g hemoglobin/L added into the plasma or serum. Similarly, the addition of simulated hemolysate to control plasma in vitro caused a 5% increase in PZC when hemoglobin concentrations reached 1.18 ± 0.10 g/L. In addition, serum samples from a population nutritional survey were scored for hemolysis and analyzed for changes in SZC; samples with hemolysis in the range of 1-2.5 g hemoglobin/L showed an estimated increase in SZC of 6% compared with nonhemolyzed samples. Each approach indicated that a 5% increase in PZC/SZC occurs at ∼1 g hemoglobin/L in plasma or serum. This concentration of hemoglobin can be readily identified directly by chemical hemoglobin assays or indirectly by direct spectrophotometry or matching to a color scale. Conclusions: A threshold of 1 g hemoglobin/L is recommended for PZC/SZC measurements to avoid increases in zinc caused by hemolysis. The use of this threshold may improve zinc assessment for monitoring zinc status and nutritional interventions.

Identification of a Hemolysis Threshold That Increases Plasma and Serum Zinc Concentration123

PubMed Central

Otoo, Gloria E; Smith, Lauren; Siekmann, Jonathan H

2017-01-01

Background: Plasma or serum zinc concentration (PZC or SZC) is the primary measure of zinc status, but accurate sampling requires controlling for hemolysis to prevent leakage of zinc from erythrocytes. It is not established how much hemolysis can occur without changing PZC/SZC concentrations. Objective: This study determines a guideline for the level of hemolysis that can significantly elevate PZC/SZC. Methods: The effect of hemolysis on PZC/SZC was estimated by using standard hematologic variables and mineral content. The calculated hemolysis threshold was then compared with results from an in vitro study and a population survey. Hemolysis was assessed by hemoglobin and iron concentrations, direct spectrophotometry, and visual assessment of the plasma or serum. Zinc and iron concentrations were determined by inductively coupled plasma spectrometry. Results: A 5% increase in PZC/SZC was calculated to result from the lysis of 1.15% of the erythrocytes in whole blood, corresponding to ∼1 g hemoglobin/L added into the plasma or serum. Similarly, the addition of simulated hemolysate to control plasma in vitro caused a 5% increase in PZC when hemoglobin concentrations reached 1.18 ± 0.10 g/L. In addition, serum samples from a population nutritional survey were scored for hemolysis and analyzed for changes in SZC; samples with hemolysis in the range of 1–2.5 g hemoglobin/L showed an estimated increase in SZC of 6% compared with nonhemolyzed samples. Each approach indicated that a 5% increase in PZC/SZC occurs at ∼1 g hemoglobin/L in plasma or serum. This concentration of hemoglobin can be readily identified directly by chemical hemoglobin assays or indirectly by direct spectrophotometry or matching to a color scale. Conclusions: A threshold of 1 g hemoglobin/L is recommended for PZC/SZC measurements to avoid increases in zinc caused by hemolysis. The use of this threshold may improve zinc assessment for monitoring zinc status and nutritional interventions. PMID:28490675

Exploring the Association of Hemoglobin Level and Adverse Events in Children with Cancer Presenting with Fever in Neutropenia

PubMed Central

Ammann, Roland A.; Niggli, Felix K.; Leibundgut, Kurt; Teuffel, Oliver; Bodmer, Nicole

2014-01-01

Background In children and adolescents with fever in neutropenia (FN) during chemotherapy for cancer, hemoglobin ≥90 g/L at presentation with FN had been associated with adverse events (AE). This analysis explored three hypothetical pathophysiological mechanisms potentially explaining this counterintuitive finding, and further analyzed the statistical association between hemoglobin and AE. Methods Two of 8 centers, reporting on 311 of 421 FN episodes in 138 of 215 patients participated in this retrospective analysis based on prospectively collected data from three databases (SPOG 2003 FN, transfusion and hematology laboratories). Associations with AE were analyzed using mixed logistic regression. Results Hemoglobin was ≥90 g/L in 141 (45%) of 311 FN episodes, specifically in 59/103 (57%) episodes with AE, and in 82/208 (39%) without (OR, 2.3; 99%CI, 1.1–4.9; P = 0.004). In FN with AE, hemoglobin was bimodally distributed with a dip around 85 g/L. There were no significant interactions for center, age and sex. In multivariate mixed logistic regression, AE was significantly and independently associated with leukopenia (leukocytes <0.3 G/L; OR, 3.3; 99%CI, 1.1–99; P = 0.004), dehydration (hemoglobinPresentation/hemoglobin8–72 hours ≥1.10 in untransfused patients; OR, 3.5; 99%CI, 1.1–11.4; P = 0.006) and non-moderate anemia (difference from 85 g/L; 1.6 per 10 g/L; 1.0–2.6; P = 0.005), but not with recent transfusion of packed red blood cells (pRBC), very recent transfusion of pRBC or platelets, or with hemoglobin ≥90 g/L as such. Conclusions Non-moderate anemia and dehydration were significantly and relevantly associated with the risk of AE in children with cancer and FN. These results need validation in prospective cohorts before clinical implementation. PMID:25020130

Detection of IgE, IgG, IgA and IgM antibodies against raw and processed food antigens

PubMed Central

Vojdani, Aristo

2009-01-01

Background Despite the first documented case of food allergy to cooked food in 1921 by Prausnitz and Kustner, all commercial food antigens are prepared from raw food. Furthermore, all IgE and IgG antibodies against dietary proteins offered by many clinical laboratories are measured against raw food antigens. Methods We developed an enzyme-linked immunosorbent assay for the measurement of IgE, IgG, IgA and IgM antibodies against raw and processed food antigens. Sera with low or high reactivity to modified food antigens were subjected to myelin basic protein, oxidized low density lipoprotein, and advanced glycation end products (AGE) such as AGE-human serum albumin and AGE-hemoglobin. Results Compared to raw food antigens, IgE antibodies showed a 3–8-fold increase against processed food antigens in 31% of the patients. Similarly, IgG, IgA and IgM antibodies against modified food antigens overall were found at much higher levels than antibody reactions against raw food antigens. Almost every tested serum with high levels of antibodies against modified food antigens showed very high levels of antibodies against myelin basic protein, oxidized low density lipoprotein, AGE-human serum albumin and AGE-hemoglobin. Conclusion We conclude that the determination of food allergy, intolerance and sensitivity would be improved by testing IgE, IgG, IgA and IgM antibodies against both raw and processed food antigens. Antibodies against modified food antigens, by reacting with AGEs and tissue proteins, may cause perturbation in degenerative and autoimmune diseases such as diabetes, atherosclerosis, inflammation, autoimmunity, neurodegeneration and neuroautoimmunity. PMID:19435515

Early trends from the Study to Evaluate the Prospective Payment System Impact on Small Dialysis Organizations (STEPPS).

PubMed

Brunelli, Steven M; Monda, Keri L; Burkart, John M; Gitlin, Matthew; Neumann, Peter J; Park, Grace S; Symonian-Silver, Margarita; Yue, Susan; Bradbury, Brian D; Rubin, Robert J

2013-06-01

Launched in January 2011, the prospective payment system (PPS) for the US Medicare End-Stage Renal Disease Program bundled payment for services previously reimbursed independently. Small dialysis organizations may be particularly susceptible to the financial implications of the PPS. The ongoing Study to Evaluate the Prospective Payment System Impact on Small Dialysis Organizations (STEPPS) was designed to describe trends in care and outcomes over the period of PPS implementation. This report details early results between October 2010 and June 2011. Prospective observational cohort study of patients from a sample of 51 small dialysis organizations. 1,873 adult hemodialysis and peritoneal dialysis patients. Secular trends in processes of care, anemia, metabolic bone disease management, and red blood cell transfusions. Facility-level data are collected quarterly. Patient characteristics were collected at enrollment and scheduled intervals thereafter. Clinical outcomes are collected on an ongoing basis. Over time, no significant changes were observed in patient to staff ratios. There was a temporal trend toward greater use of peritoneal dialysis (from 2.4% to 3.6%; P = 0.09). Use of cinacalcet, phosphate binders, and oral vitamin D increased; intravenous (IV) vitamin D use decreased (P for trend for all <0.001). Parathyroid hormone levels increased (from 273 to 324 pg/dL; P < 0.001). Erythropoiesis-stimulating agent doses decreased (P < 0.001 for IV epoetin alfa and IV darbepoetin alfa), particularly high doses. Mean hemoglobin levels decreased (P < 0.001), the percentage of patients with hemoglobin levels <10 g/dL increased (from 12.7% to 16.8%), and transfusion rates increased (from 14.3 to 19.6/100 person-years; P = 0.1). Changes in anemia management were more pronounced for African American patients. Limited data were available for the prebundle period. Secular trends may be subject to the ecologic fallacy and are not causal in nature. In the period after PPS implementation, IV vitamin D use decreased, use of oral therapies for metabolic bone disease increased, erythropoiesis-stimulating agent use and hemoglobin levels decreased, and transfusion rates increased numerically. Copyright © 2013 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Oral vitamin C supplementation reduces erythropoietin requirement in hemodialysis patients with functional iron deficiency.

PubMed

Sultana, Tanjim; DeVita, Maria V; Michelis, Michael F

2016-09-01

Functional iron deficiency (FID) is a major cause of persistent anemia in dialysis patients and also contributes to a suboptimal response to erythropoietin (Epo) administration. Vitamin C acts as an enzyme cofactor and enhances mobilization of the ferrous form of iron to transferrin thus increasing its bioavailability. High-dose intravenous vitamin C has been shown to decrease the Epo requirement and improve hemoglobin levels in previous studies. This study assessed the effect of low-dose oral vitamin C on possible reduction in Epo dose requirements in stable hemodialysis patients with FID. This prospective study included 22 stable hemodialysis patients with FID defined as transferrin saturation (T sat) <30 % and ferritin levels of >100 mcg/L with Epo requirement of ≥4000 U/HD session. Patients received oral vitamin C 250 mg daily for 3 months. Hemoglobin, iron and T sat levels were recorded monthly. No one received iron supplementation during the study period. There was a significant reduction in median Epo dose requirement in the 15 patients who completed the study, from 203.1 U/kg/week (95 % CI 188.4-270.6) to 172.8 U/kg/week (95 % CI 160.2-214.8), (P = 0.01). In the seven responders, there was 33 % reduction in Epo dose from their baseline. Despite adjustment of Epo dose, the mean hemoglobin level was significantly increased from 10.1 ± 0.6 to 10.7 ± 0.6 mg/dL (P = 0.03). No adverse effects of oral vitamin C were observed. Daily low-dose oral vitamin C supplementation reduced Epo dose requirements in hemodialysis patients with FID. Limitations of this study include a small sample size and the lack of measurements of vitamin C and oxalate levels. Despite concerns regarding oral vitamin C absorption in dialysis patients, this study indicates vitamin C was well tolerated by all participants without reported adverse effect.

Euthyroid submedian free T4 and subclinical hypothyroidism may have a detrimental clinical effect in Down syndrome.

PubMed

Tenenbaum, Ariel; Lebel, Eyal; Malkiel, Sarah; Kastiel, Yael; Abulibdeh, Abdulsalam; Zangen, David Haim

2012-01-01

Aberrant thyroid function is highly prevalent in Down syndrome (DS). We aimed to find whether subclinical hypothyroidism (SCH) or low-normal free T4 (FT4) are associated with a detrimental clinical outcome in untreated DS patients. 157 patients assessed at Hadassah Down Syndrome Center between 2004 and 2010 by comprehensive clinical evaluation and tests for hemoglobin, FT4 and thyroid-stimulating hormone (TSH) were subdivided into subgroups including: clinical hypothyroidism, SCH, euthyroid submedian or supramedian FT4, and alternatively for euthyroidism and TSH levels (submedian or supramedian TSH). Hypothyroidism was found in 21.7% and SCH in another 14.9% of the patients. Moderate/severe hypotonia were more frequent among SCH patients compared to euthyroid patients (52.6 vs. 16.4%, p = 0.002). Patient's hemoglobin levels were lower in the euthyroid submedian FT4 group compared to the euthyroid supramedian FT4 group (10.9 vs. 0% below the normal range, p = 0.001). Interestingly, FT4 levels correlated negatively with increasing age among euthyroid DS patients (Pearson's correlation coefficient = -0.324, p = 0.009). SCH and euthyroid submedian FT4 may have significant clinical sequelae, such as hypotonia and anemia. Interventional studies with L-thyroxine replacement may be indicated in these subpopulations. Our finding that FT4 levels decrease with age in DS (contrasting the general population trend) may indicate redefining the normal FT4 levels range in DS. Copyright © 2012 S. Karger AG, Basel.

Late-life Hemoglobin and the Incidence of Parkinson’s Disease

PubMed Central

Abbott, Robert D.; Ross, G. Webster; Tanner, Caroline M.; Andersen, Julie K.; Masaki, Kamal H.; Rodriguez, Beatriz L.; White, Lon R.; Petrovitch, Helen

2010-01-01

Background Brain iron promotes neurodegeneration in Parkinson’s disease (PD). While hemoglobin (Hb) is the most abundant source of peripheral iron in humans, its relationship with PD is uncertain. This report examines the association between Hb in late-life and PD incidence. Methods From 1991-1993, Hb was measured in 3,507 men in the Honolulu-Asia Aging Study. Men were aged 71-93 years and without PD. Participants were followed until 2001 for incident PD. Results Hb levels declined markedly with age. For men aged 71-75 years, 14.8% had levels <14 g/dL versus 53.6% in those aged 86 and older (p<0.001). During follow-up, 47 men developed PD (19.8/10,000 person-years). After age-adjustment, PD incidence rose significantly from 10.3 to 34.9/10,000 person-years as Hb increased from <14 to ≥16 g/dL (p=0.024, relative hazard 3.2, 95% CI 1.2-8.9). Associations persisted after accounting for early mortality and adjustments for concomitant risk factors. Conclusions While Hb declines with advancing age, evidence suggests that Hb that remains high in elderly men is associated with an increased risk of PD. PMID:20709430

Long-Term Single and Joint Effects of Excessive Daytime Napping on the HOMA-IR Index and Glycosylated Hemoglobin: A Prospective Cohort Study.

PubMed

Li, Xue; Pang, Xiuyu; Zhang, Qiao; Qu, Qiannuo; Hou, Zhigang; Liu, Zhipeng; Lv, Lin; Na, Guanqiong; Zhang, Wei; Sun, Changhao; Li, Ying

2016-02-01

This prospective cohort study was conducted to assess the duration of daytime napping and its effect combined with night sleep deprivation on the risk of developing high HOMA-IR (homeostasis model assessment of insulin resistance) index and disadvantageous changes in glycosylated hemoglobin (HbA1c) levels.A total of 5845 diabetes-free subjects (2736 women and 3109 men), 30 to 65 years of age, were targeted for this cohort study since 2008. Multiple adjusted Cox regression models were performed to evaluate the single and joint effects of daytime napping on the risk of an elevated HbA1c level and high HOMA-IR index.After an average of 4.5 years of follow-up, >30 minutes of daytime napping was significantly associated with an increased risk of an elevated HbA1c level (>6.5%) in men and women (all P trend < 0.05). Hazard ratios (HRs) for an HbA1c level between 5.7% and 6.4% were also significant in the entire cohort and women, but nonsignificant in men. HRs (95% confidence interval, CIs) for the high HOMA-IR index in the entire cohort, men, and women were 1.33 (1.10-1.62), 1.46 (1.08-1.98), and 1.47 (1.12-1.91), respectively. The combination of sleep deprivation with no naps or >30 minutes napping and the combination of no sleep deprivation with >30 minutes daytime napping were all associated with an HbA1c level >6.5% (HR = 2.08, 95% CI = 1.24-3.51; HR = 4.00, 95% CI = 2.03-7.90; and HR = 2.05, 95% CI = 1.29-3.27, respectively). No sleep deprivation combined with >30 minutes daytime napping correlated with a high risk of an HbA1c level between 5.7% and 6.4% and high HOMA-IR index (HR = 2.12, 95% CI = 1.48-3.02; and HR = 1.35, 95% CI = 1.10-1.65, respectively).Daytime napping >30 minutes was associated with a high risk of an elevated HbA1c level and high HOMA-IR index. No sleep deprivation combined with napping >30 minutes carries a risk of abnormal glucose metabolism. Sleep deprivation combined with brief daytime napping <30 minutes was not associated with a risk for an elevated HbA1c level and high HOMA-IR index.

Long-Term Single and Joint Effects of Excessive Daytime Napping on the HOMA-IR Index and Glycosylated Hemoglobin

PubMed Central

Li, Xue; Pang, Xiuyu; Zhang, Qiao; Qu, Qiannuo; Hou, Zhigang; Liu, Zhipeng; Lv, Lin; Na, Guanqiong; Zhang, Wei; Sun, Changhao; Li, Ying

2016-01-01

Abstract This prospective cohort study was conducted to assess the duration of daytime napping and its effect combined with night sleep deprivation on the risk of developing high HOMA-IR (homeostasis model assessment of insulin resistance) index and disadvantageous changes in glycosylated hemoglobin (HbA1c) levels. A total of 5845 diabetes-free subjects (2736 women and 3109 men), 30 to 65 years of age, were targeted for this cohort study since 2008. Multiple adjusted Cox regression models were performed to evaluate the single and joint effects of daytime napping on the risk of an elevated HbA1c level and high HOMA-IR index. After an average of 4.5 years of follow-up, >30 minutes of daytime napping was significantly associated with an increased risk of an elevated HbA1c level (>6.5%) in men and women (all P trend < 0.05). Hazard ratios (HRs) for an HbA1c level between 5.7% and 6.4% were also significant in the entire cohort and women, but nonsignificant in men. HRs (95% confidence interval, CIs) for the high HOMA-IR index in the entire cohort, men, and women were 1.33 (1.10–1.62), 1.46 (1.08–1.98), and 1.47 (1.12–1.91), respectively. The combination of sleep deprivation with no naps or >30 minutes napping and the combination of no sleep deprivation with >30 minutes daytime napping were all associated with an HbA1c level >6.5% (HR = 2.08, 95% CI = 1.24–3.51; HR = 4.00, 95% CI = 2.03–7.90; and HR = 2.05, 95% CI = 1.29–3.27, respectively). No sleep deprivation combined with >30 minutes daytime napping correlated with a high risk of an HbA1c level between 5.7% and 6.4% and high HOMA-IR index (HR = 2.12, 95% CI = 1.48–3.02; and HR = 1.35, 95% CI = 1.10–1.65, respectively). Daytime napping >30 minutes was associated with a high risk of an elevated HbA1c level and high HOMA-IR index. No sleep deprivation combined with napping >30 minutes carries a risk of abnormal glucose metabolism. Sleep deprivation combined with brief daytime napping <30 minutes was not associated with a risk for an elevated HbA1c level and high HOMA-IR index. PMID:26844520

Interleukin 8 as a vaso-occlusive marker in Brazilian patients with sickle cell disease.

PubMed

Gonçalves, M S; Queiroz, I L; Cardoso, S A; Zanetti, A; Strapazoni, A C; Adorno, E; Albuquerque, A; Sant'Ana, A; dos Reis, M G; Barral, A; Barral Netto, M

2001-10-01

Sickle cell disease has a worldwide distribution and is a public health problem in Brazil. Although vaso-occlusive crisis (VOC) is one of the most important clinical features of the disease, there are still several steps of its pathogenesis which are unknown. The increase of the chemotactic factor interleukin 8 (IL-8) has been reported to be involved in sickle cell disease crisis, but this has not been demonstrated conclusively. In the present study we analyzed serum IL-8 levels by ELISA and hematological parameters and hemoglobin patterns by standard techniques in 23 (21 SS and 2 SC) Brazilian patients with sickle cell syndromes during VOC caused by different inducing factors, 22 (21 SS and 1 SC) sickle cell patients out of crisis, and 11 healthy controls. Increased IL-8 levels were observed in 19 of 23 VOC patients (79.2%), 3 of them with more than 1,000 pg/ml. Seventeen of 22 (77.3%) non-crisis patients showed low IL-8 levels (less than 15 pg/ml). Healthy controls had low IL-8 levels. A significant difference in serum IL-8 levels was observed between crisis and non-crisis sickle cell patients (P<0.0001). There was no correlation between IL-8 levels and hematological data or hemoglobin patterns. High serum IL-8 levels were observed in VOC patients independently of the crisis-inducing factor. We conclude that in the studied population, IL-8 concentration may be a useful VOC marker, although the mechanism of the pathogenic process of sickle cell VOC syndromes remains unclear.

Influence of socioeconomic and psychological factors in glycemic control in young children with type 1 diabetes mellitus.

PubMed

Andrade, Carlos Jefferson do Nascimento; Alves, Crésio de Aragão Dantas

2018-01-04

To evaluate the influence of socioeconomic and psychological factors on glycemic control in young children with type 1 diabetes mellitus. This was a cross-sectional study assessing prepubertal children with type 1 diabetes mellitus. The authors analyzed the socioeconomic status using the Brazil Economic Classification Criterion (Critério de Classificação Econômica Brasil [CCEB]) and psychological conditions through the Brazilian version of the Problem Areas in Diabetes, associated with glycemic control, measured by glycated hemoglobin (HbA1c). Descriptive analysis was used. The variables were assessed by bivariate and multivariate robust Poisson regression model, as well as Fisher's exact and Pearson's chi-squared tests to obtain the ratios of gross and adjusted prevalence ratio, with confidence interval being estimated at 95%. A total of 68 children with type 1 diabetes mellitus were included in the study. A negative association between glycemic control (glycated hemoglobin levels), socioeconomic status (Brazil Economic Classification Criterion), and psychological condition (Brazilian version of the Problem Areas in Diabetes) was observed. Among the study participants, 73.5% (n=50) of the children had an unfavorable socioeconomic status; these participants were 1.4 times more likely to present altered glycated hemoglobin values. In relation to individuals with compromised psychological status, 26 (38.2%) had a score above 70, thus being classified with psychological stress; these children were 1.68 times more likely (95% confidence interval: 1.101, 1.301) to have higher glycated hemoglobin levels. The socioeconomic conditions and psychological characteristics of the study participants were negatively associated with glycated hemoglobin results. These data reinforce the importance of the studied variables as predictors of glycemic control. Copyright © 2017. Published by Elsevier Editora Ltda.

Erratum to: Blood HbO2 and HbCO2 dissociation curves at varied O2, CO2, pH, 2,3-DPG and temperature levels.

PubMed

Dash, Ranjan K; Bassingthwaighte, James B

2010-04-01

New mathematical model equations for O(2) and CO(2) saturations of hemoglobin (S(HbO)(2) and S(HbCO)(2) are developed here from the equilibrium binding of O(2) and CO(2) with hemoglobin inside RBCs. They are in the form of an invertible Hill-type equation with the apparent Hill coefficients KHbO(2) and KHbCO(2) in the expressions for SHbO(2) and SHbCO(2) dependent on the levels of O(2) and CO(2) partial pressures (P(O)(2) and P(CO)(2)), pH, 2,3-DPG concentration, and temperature in blood. The invertibility of these new equations allows PO(2) and PCO(2) to be computed efficiently from S(HbO)(2) and S(HbCO)(2) and vice versa. The oxyhemoglobin (HbO(2)) and carbamino-hemoglobin (HbCO(2)) dissociation curves computed from these equations are in good agreement with the published experimental and theoretical curves in the literature. The model solutions describe that, at standard physiological conditions, the hemoglobin is about 97.2% saturated by O(2) and the amino group of hemoglobin is about 13.1% saturated by CO(2). The O(2) and CO(2) content in whole blood are also calculated here from the gas solubilities, hematocrits, and the new formulas for S(HbO)(2) and S(HbCO)(2). Because of the mathematical simplicity and invertibility, these new formulas can be conveniently used in the modeling of simultaneous transport and exchange of O(2) and CO(2) in the alveoli-blood and blood-tissue exchange systems.

The High Prevalence of Anemia in Cambodian Children and Women Cannot Be Satisfactorily Explained by Nutritional Deficiencies or Hemoglobin Disorders

PubMed Central

Wieringa, Frank Tammo; Dahl, Miriam; Chamnan, Chhoun; Poirot, Etienne; Kuong, Khov; Sophonneary, Prak; Sinuon, Muth; Greuffeille, Valerie; Hong, Rathavuth; Berger, Jacques; Dijkhuizen, Marjoleine Amma; Laillou, Arnaud

2016-01-01

Background: Anemia is highly prevalent in Cambodian women and children, but data on causes of anemia are scarce. We performed a national micronutrient survey in children and women that was linked to the Cambodian Demographic Health Survey 2014 (CDHS-2014) to assess the prevalence of micronutrient deficiency, hemoglobin disorders and intestinal parasite infection. Methods: One-sixth of households from the CDHS-2014 were selected for a follow-up visit for the micronutrient survey. Households were visited from two weeks to two months after the CDHS-2014 visit. Data on micronutrient status were available for 1512 subjects (792 children and 720 women). Results: Anemia was found in 43% of the women and 53% of the children. Hemoglobin disorders affected >50% of the population, with Hemoglobin-E the most prevalent disorder. Deficiencies of iron (ferritin < 15 g/L), vitamin A (retinol-binding-protein (RBP) < 0.70 mol/L) or vitamin B12 (<150 pmol/L) were not prevalent in the women (<5% for all), whereas 17.8% of the women had low concentrations of folic acid (<10 nmol/L). In the children, the prevalence of iron, vitamin A, vitamin B12 or folic acid deficiency was <10%. Zinc deficiency, hookworm infection and hemoglobinopathy were significantly associated with anemia in children, whereas in the women none of the factors was significantly associated with anemia. Iron deficiency anemia (IDA) was more prevalent in children <2 years, but in older children and women, the prevalence of IDA was <5%. The most prevalent, preventable causes of anemia were hookworm infection and zinc and folic acid deficiency. Over 40% of the anemia was not caused by nutritional factors. Conclusion: The very high prevalence of anemia in Cambodian women and children cannot be explained solely by micronutrient deficiencies and hemoglobin disorders. Micronutrient interventions to improve anemia prevalence are likely to have limited impact in the Cambodian setting. The focus of current interventions to reduce the high prevalence of anemia in children and women should be broadened to include zinc and folic acid as well as effective anti-hookworm measures. PMID:27338454

Diagnostic yield and predictive factors of findings in small-bowel capsule endoscopy in the setting of iron-deficiency anemia.

PubMed

Olano, Carolina; Pazos, Ximena; Avendaño, Karla; Calleri, Alfonso; Ketzoian, Carlos

2018-06-01

 Despite the widespread use of small-bowel capsule endoscopy (CE), there is still limited data on its utility and effectiveness for the diagnosis and management of patients with iron-deficiency anemia (IDA).  To assess the diagnostic yield of CE and the factors predicting positive findings in patients with IDA.  Patients with unexplained IDA and negative upper and lower endoscopy were included. A positive diagnostic yield was considered when CE diagnosed one or more lesions that could explain the IDA. Sex, age, NSAID consumption, blood transfusion requirement, and ferritin and hemoglobin levels were recorded.  In total, 120 CE were included (mean age 58.5 years; F/M 82:38). Mean hemoglobin levels were 9 g/dL and mean ferritin levels were 15.7 ng/mL. Positive findings were present in 50 % of patients. The most frequent was angiodysplasia (45 %). Despite several baseline variables being significantly associated with positive findings, using a logistic regression model, it was verified that male sex (OR 3.93; 95 %CI 1.57 - 9.86), age (OR 1.03; 95 %CI 1.00 - 1.06), and hemoglobin levels (OR 0.73; 95 %CI 0.57 - 0.94) were the variables having an independent effect on the probability of obtaining positive findings. Age older than 50 years (OR 14.05; 95 %CI 1.69 - 116.23) and male sex (OR 3.63; 95 %CI 1.29 - 10.17) were the variables which increased the risk of diagnosing angiodysplasia.  CE is a useful technique in patients with IDA. To improve its yield, it is necessary to select patients carefully. Male sex, older age, and low hemoglobin levels were associated with a risk of positive finding in this group of patients. The risk of diagnosing angiodysplasia increased with male sex and older age.

Factors associated with the nutritional status of children less than 5 years of age

PubMed Central

Miglioli, Teresa Cristina; Fonseca, Vania Matos; Gomes, Saint Clair; da Silva, Katia Silveira; de Lira, Pedro Israel Cabral; Batista, Malaquias

2015-01-01

OBJECTIVE To analyze if the nutritional status of children aged less than five years is related to the biological conditions of their mothers, environmental and socioeconomic factors, and access to health services and social programs. METHODS This cross-sectional population-based study analyzed 664 mothers and 790 children using canonical correlation analysis. Dependent variables were characteristics of the children (weight/age, height/age, BMI/age, hemoglobin, and retinol serum levels). Independent variables were those related to the mothers’ nutritional status (BMI, hemoglobin, and retinol serum levels), age, environmental and socioeconomic factors and access to health service and social programs. A < 0.05 significance level was adopted to select the interpreted canonical functions (CF) and ± 0.40 as canonical load value of the analyzed variables. RESULTS Three canonical functions were selected, concentrating 89.9% of the variability of the relationship among the groups. In the first canonical function, weight/age (-0.73) and height/age (-0.99) of the children were directly related to the mother’s height (-0.82), prenatal appointments (-0.43), geographical area of the residence (-0.41), and household income per capita (-0.42). Inverse relationship between the variables related to the children and people/room (0.44) showed that the larger the number of people/room, the poorer their nutritional status. Rural residents were found to have the worse nutritional conditions. In the second canonical function, the BMI of the mother (-0.48) was related to BMI/age and retinol of the children, indicating that as women gained weight so did their children. Underweight women tended to have children with vitamin A deficiency. In the third canonical function, hemoglobin (-0.72) and retinol serum levels (-0.40) of the children were directly related to the mother’s hemoglobin levels (-0.43). CONCLUSIONS Mothers and children were associated concerning anemia, vitamin A deficiency and anthropometric markers. Living in rural areas is a determining factor for the families health status. PMID:26398874

Demographic details, clinical features, and nutritional characteristics of young adults with Type 1 diabetes mellitus - A South Indian tertiary center experience.

PubMed

Joseph, Mini; Shyamasunder, Asha H; Gupta, Riddhi D; Anand, Vijayalakshmi; Thomas, Nihal

2016-01-01

Type 1 diabetes mellitus (T1DM) accounts for 5-10% of all diagnosed diabetes and the highest incidence is found in India. The main objectives were to study the demographic, clinical, and nutritional characteristics of young adults with T1DM and its effect glycosylated hemoglobin levels. This cross-sectional study was conducted among young adults with T1DM (18-45 years of age) in a tertiary hospital in South India. Data were obtained from updated medical records. The dietary data were assessed from food diaries and 24 h recall method. Anthropometry was determined. The analysis revealed that socio-economic variables did not affect the glycosylated hemoglobin levels. The mean glycosylated hemoglobin value was 8.81 ± 2.38%. Nearly, half the patients were malnourished. The overall dietary intake was inadequate. The multivariate regression model, adjusted for confounding factors such as gender, age, and body mass index, revealed that only duration of diabetes and protein intake were significant predictors of glycosylated hemoglobin status ( P < 0.005). Integrated care provided at subsidized cost has been pivotal in effective diabetes management. However, there is an urgent need to educate our patients on nutrition therapy. T1DM patients need specialized advice to ensure appropriately balanced nutrition that has a significant impact on their long-term glycemic control.

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

PubMed Central

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

2008-01-01

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

Blood conservation strategies to reduce the need for red blood cell transfusion in critically ill patients

PubMed Central

Tinmouth, Alan T.; McIntyre, Lauralynn A.; Fowler, Robert A.

2008-01-01

Anemia commonly affects critically ill patients. The causes are multifactorial and include acute blood loss, blood loss from diagnostic testing and blunted red blood cell production. Blood transfusions are frequently given to patients in intensive care units to treat low hemoglobin levels due to either acute blood loss or subacute anemia associated with critical illness. Although blood transfusion is a life-saving therapy, evidence suggests that it may be associated with an increased risk of morbidity and mortality. A number of blood conservation strategies exist that may mitigate anemia in hospital patients and limit the need for transfusion. These strategies include the use of hemostatic agents, hemoglobin substitutes and blood salvage techniques, the reduction of blood loss associated with diagnostic testing, the use of erythropoietin and the use of restrictive blood transfusion triggers. Strategies to reduce blood loss associated with diagnostic testing and the use of hemostatic agents and erythropoietin result in higher hemoglobin levels, but they have not been shown to reduce the need for blood transfusions or to improve clinical outcomes. Lowering the hemoglobin threshold at which blood is transfused will reduce the need for transfusions and is not associated with increased morbidity or mortality among most critically ill patients without active cardiac disease. Further research is needed to determine the potential roles for other blood conservation strategies. PMID:18166731

The prognostic significance of prostate specific antigen in metastatic hormone-resistant prostate cancer.

PubMed Central

Fosså, S. D.; Waehre, H.; Paus, E.

1992-01-01

Twenty-seven of 152 patients (18%) with progressing hormone resistant prostate cancer had normal serum levels of prostate specific antigen (PSA less than or equal to 10 micrograms l-1), when referred for secondary treatment. PSA was significantly correlated with the extent of skeletal metastases (R: 0.35) and the levels of hemoglobin (R: -0.19) and serum alkaline phosphatase (R: 0.30). In a multivariate Cox regression analysis the survival of the 152 patients was not correlated with the PSA level but with the patients performance status, the level of hemoglobin, and the time between primary hormone treatment and relapse. The lack of serum PSA to predict survival may be explained by a heterogenous composition of hormone resistant prostate cancer as regards differentiated and/or PSA producing vs undifferentiated and/or PSA non-producing cells. PMID:1379059

Selective Removal of Hemoglobin from Blood Using Hierarchical Copper Shells Anchored to Magnetic Nanoparticles

PubMed Central

Wang, Yaokun; Yan, Mingyang

2017-01-01

Hierarchical copper shells anchored on magnetic nanoparticles were designed and fabricated to selectively deplete hemoglobin from human blood by immobilized metal affinity chromatography. Briefly, CoFe2O4 nanoparticles coated with polyacrylic acid were first synthesized by a one-pot solvothermal method. Hierarchical copper shells were then deposited by immobilizing Cu2+ on nanoparticles and subsequently by reducing between the solid CoFe2O4@COOH and copper solution with NaBH4. The resulting nanoparticles were characterized by scanning electron microscopy, transmission electron microscopy, Fourier transform infrared spectrometry, X-ray photoelectron spectroscopy, and vibrating sample magnetometry. The particles were also tested against purified bovine hemoglobin over a range of pH, contact time, and initial protein concentration. Hemoglobin adsorption followed pseudo-second-order kinetics and reached equilibrium in 90 min. Isothermal data also fit the Langmuir model well, with calculated maximum adsorption capacity 666 mg g−1. Due to the high density of Cu2+ on the shell, the nanoparticles efficiently and selectively deplete hemoglobin from human blood. Taken together, the results demonstrate that the particles with hierarchical copper shells effectively remove abundant, histidine-rich proteins, such as hemoglobin from human blood, and thereby minimize interference in diagnostic and other assays. PMID:28316987

Purification and spectroscopic characterization of Ctb, a group III truncated hemoglobin implicated in oxygen metabolism in the food-borne pathogen Campylobacter jejuni†

PubMed Central

Wainwright, Laura M.; Wang, Yinghua; Park, Simon F.; Yeh, Syun-Ru; Poole, Robert K.

2008-01-01

Campylobacter jejuni is a foodborne bacterial pathogen that possesses two distinct hemoglobins, encoded by the ctb and cgb genes. The former codes for a truncated hemoglobin (Ctb) in group III, an assemblage of uncharacterized globins in diverse clinically- and technologically-significant bacteria. Here, we show that Ctb purifies as a monomeric, predominantly oxygenated species. Optical spectra of ferric, ferrous, O2- and CO-bound forms resemble those of other hemoglobins. However, resonance Raman analysis shows Ctb to have an atypical νFe-CO stretching mode at 514 cm-1, compared to the other truncated hemoglobins that have been characterized so far. This implies unique roles in ligand stabilisation for TyrB10, HisE7 and TrpG8, residues highly conserved within group III truncated hemoglobins. Since C. jejuni is a microaerophile, and a ctb mutant exhibits O2-dependent growth defects, one of the hypothesised roles of Ctb is in the detoxification, sequestration or transfer of O2 The midpoint potential (Eh) of Ctb was found to be −33 mV, but no evidence was obtained in vitro to support the hypothesis that Ctb is reducible by NADH or NADPH. This truncated hemoglobin may function in the facilitation of O2 transfer to one of the terminal oxidases of C. jejuni or instead facilitate O2 transfer to Cgb for NO detoxification. PMID:16681372

Solid-Phase Extraction of Hemoglobin from Human Whole Blood with a Coordination-Polymer-Derived Composite Material Based on ZnO and Mesoporous Carbon.

PubMed

Jia, Yuan; Xu, Xinxin; Ou, Jinzhao; Liu, Xiaoxia

2017-11-13

A composite material, ZnO@MC, has been synthesized successfully by calcination using a one-dimensional zinc-based coordination polymer as the precursor. In ZnO@MC, ZnO particles with a size of about 5-8 nm are dispersed evenly in a mesoporous carbon matrix. Adsorption experiments at pH 6.8 with 2 mg ZnO@MC as adsorbent illustrated an adsorption efficiency of 92.3 % in 5 mL hemoglobin (Hb) solution with a concentration of 100 mg L -1 . In contrast, the adsorption of bovine serum albumin can almost be ignored under the same conditions. The selectivity originates from a strong Zn II -histidine interaction between ZnO@MC and hemoglobin. The adsorption behavior of hemoglobin on ZnO@MC fits the Temkin model perfectly with a capacity as high as 11646 mg g -1 . The hemoglobin adsorbed on the composite material can be eluted easily with sodium dodecyl sulfate stripping reagent with an extraction efficiency of 87.7 %. Circular dichroism spectra and protein activity studies suggest the structure and biological activity of hemoglobin is the same before and after the adsorption/desorption experiment. Finally, the ZnO@MC composite material was employed to extract hemoglobin from human whole blood without any pretreatment, and gave a very satisfactory result. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

[Importance of binding of 2,3-diphosphoglycerate and ATP to hemoglobin for erythrocyte glycolysis: activation by 2,3-diphosphoglycerate of hexokinase at intracellular conditions].

PubMed

Geier, T; Glende, M; Reich, J G

1978-01-01

In a theoretical study the influence of hemoglobin and Mg-ions as binding partners of red cell 2,3-diphosphoglycerate and ATP was investigated. Free hemoglobin may be an efficient competitor of Mg2+ for the ligand ATP. At conditions which favour hemoglobin as binding partner (i.e. desoxygenation, low medium pH and incubation temperature, as in blood preservation) up to 95% of the whole cellular ATP (ca. 2mM in cell water) may be bound to hemoglobin (ca. 7 mM). This binding is largely prevented in the presence of physiological amounts of diphosphoglycerate (ca. 7 mM) which is in excess and has a higher binding affinity to hemoglobin. Therefore, diphosphoglycerate keeps ATP (MgATP) in cell water solution at conditions in which Hb would trop it in the presence of Mg2+ (ca. 3mM). It can be calculated that, by lack of free MgATP, the activity of hexokinase within the cell drops by a factor of greater than 10 when diphosphoglycerate is metabolized. This indirect activation by diphosphoglycerate of hexokinase is operative at free concentrations of DPG far below those which exert the well known excess inhibitory effect on hexokinase and phosphofructokinase. In a model study, the activation by diphosphoglycerate of the initial two-kinase stage was introduced into a simplified kinetic model of glycolysis. A pronounced hysteresis loop of the stationary concentrations of ATP and diphosphoglycerate was produced indicating the existence of several stationary states, one with high ATP and high diphosphoglycerate, the other one with low values. It is demonstrated that diphosphoglycerate, being a protector of glycolysis at physiological concentrations, triggers an autocatalytic breakdown of the energy state when permitted to drop to low values.