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.

Unloading oxygen in a capillary vessel under a pathological condition.

PubMed

Escobar, C; Méndez, F

2008-10-01

In this work, we study theoretically the unloading of oxygen from a hemoglobin molecule to the wall of a typical capillary vessel, considering that the hemoglobin under pathological conditions, obeys the rheological Maxwell model. Based on recent experimental evidences in hypertension, we consider that the red blood cells (RBCs) are composed by a single continuous medium in contrast with the classical particulate or discrete RBC models, which are only valid under normal physiological conditions. The analysis considers the hemodynamic interactions between the plasma and the hemoglobin, both circulating in a long horizontal capillary. We apply numerical and analytical methods to obtain the main fluid-dynamic characteristics for both fluids in the limit of low Reynolds and Womersley numbers. A diffusion boundary layer formulation for the oxygen transport in the combined plasma-hemoglobin core region is presented. The main aspects derived are the time and spatial evolution of the membrane. The hemoglobin and plasma velocities and the pressure distributions are shown. For the oxygen unloading the results are the oxy-hemoglobin saturation, the oxygen flux and the oxygen concentration in the cell-free plasma layer. The volume fraction of red blood cells and the Strouhal number have a great influence on the hemodynamic interactions.

Hemoglobin C disease

MedlinePlus

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

Sickle cell anemia

MedlinePlus

Anemia - sickle cell; Hemoglobin SS disease (Hb SS); Sickle cell disease ... Sickle cell anemia is caused by an abnormal type of hemoglobin called hemoglobin S. Hemoglobin is a protein inside red blood cells ...

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.

Anemia of Inflammation and Chronic Disease

MedlinePlus

... of red blood cells or the amount of hemoglobin in the red blood cells drops below normal, ... prevents the body’s cells from getting enough oxygen. Hemoglobin is an iron-rich protein that gives blood ...

Long-term Effects on the Histology and Function of Livers and Spleens in Rats after 33% Toploading of PEG-PLA-nano Artificial Red Blood Cells

PubMed Central

Liu, Zun Chang; Chang, Thomas M.S.

2012-01-01

This study is to investigate the long-term effects of nanodimension PEG-PLA artificial red blood cells containing hemoglobin and red blood cell enzymes on the liver and spleen after 1/3 blood volume top loading in rats. The experimental rats received one of the following infusions: Nano artificial red blood cells in Ringer lactate, Ringer lactate, stroma-free hemoglobin, polyhemoglobin, and autologous rat whole blood. Blood samples were taken before infusions and on days 1, 7, and 21 after infusions for analysis. Nano artificial red blood cells, polyhemoglobin, Ringer lactate and rat red blood cells did not have any significant adverse effects on alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, creatine kinase, amylase and creatine kinase. On the other hand, stroma-free hemoglobin induced significant adverse effects on liver as shown by elevation in alanine aminotransferase and aspartate aminotransferase throughout the 21 days. On day 21 after infusions rats were sacrificed and livers and spleens were excised for histological examination. Nano artificial red blood cells, polyhemoglobin, Ringer lactate and rat red blood cells did not cause any abnormalities in the microscopic histology of the livers and spleens. In the stroma-free hemoglobin group the livers showed accumulation of hemoglobin in central veins and sinusoids, and hepatic steatosis. In conclusion, injected nano artificial red blood cells can be efficiently metabolized and removed by the reticuloendothelial system, and do not have any biochemical or histological adverse effects on the livers or the spleens. PMID:19043818

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 role of facilitated diffusion in oxygen transport by cell-free hemoglobins: implications for the design of hemoglobin-based oxygen carriers.

PubMed

McCarthy, M R; Vandegriff, K D; Winslow, R M

2001-08-30

We compared rates of oxygen transport in an in vitro capillary system using red blood cells (RBCs) and cell-free hemoglobins. The axial PO(2) drop down the capillary was calculated using finite-element analysis. RBCs, unmodified hemoglobin (HbA(0)), cross-linked hemoglobin (alpha alpha-Hb) and hemoglobin conjugated to polyethylene-glycol (PEG-Hb) were evaluated. According to their fractional saturation curves, PEG-Hb showed the least desaturation down the capillary, which most closely matched the RBCs; HbA(0) and alpha alpha-Hb showed much greater desaturation. A lumped diffusion parameter, K*, was calculated based on the Fick diffusion equation with a term for facilitated diffusion. The overall rates of oxygen transfer are consistent with hemoglobin diffusion rates according to the Stokes-Einstein Law and with previously measured blood pressure responses in rats. This study provides a conceptual framework for the design of a 'blood substitute' based on mimicking O(2) transport by RBCs to prevent autoregulatory changes in blood flow and pressure.

In vitro photoacoustic measurement of hemoglobin oxygen saturation using a single pulsed broadband supercontinuum laser source.

PubMed

Lee, Changho; Jeon, Mansik; Jeon, Min Yong; Kim, Jeehyun; Kim, Chulhong

2014-06-20

We have utilized a single pulsed broadband supercontinuum laser source to photoacoustically sense total hemoglobin concentration (HbT) and oxygen saturation of hemoglobin (SO2) in bloods in vitro. Unlike existing expensive and bulky laser systems typically used for functional photoacoustic imaging (PAI), our laser system is relatively cost-effective and compact. Instead of using two single wavelengths, two wavelength bands were applied to distinguish the concentrations of two different chromophores in the mixture. In addition, we have successfully extracted the total dye concentration and the ratio of the red dye concentration to the total dye concentration in mixed red and blue dye solutions in phantoms. The results indicate that PAI with a cheap and compact fiber based laser source can potentially provide HbT and SO2 in live animals in vivo.

Use of supernatant refractive index and supernatant hemoglobin concentration to assess residual glycerol concentration in cryopreserved red blood cells.

PubMed

Wong, Kenneth A; Nsier, Nada; Acker, Jason P

2009-10-01

Red blood cells (RBCs) cryopreserved in glycerol must be deglycerolized prior to transfusion. The adequacy of glycerol removal is commonly assessed by measurement of the refractive index (RI) of the supernatant fluid. However, the presence of free hemoglobin in the supernatant falsely increases the RI and may lead to discard of units that have an acceptable residual glycerol concentration. We performed an analysis of the diagnostic accuracy of 3 methods for residual glycerol measurement - refractometry, osmometry, and a glycerol assay kit. Residual glycerol measurement using these methods was performed on 12 deglycerolized, citrate-phosphate-dextrose (CPD)/saline-adenine-glucose-mannitol (SAGM) leukoreduced RBCs. A calculation that estimates the glycerol concentration based on the refractive index and supernatant hemoglobin concentration was developed and ensures that units with an elevated RI due to the presence of hemoglobin are not discarded if their residual glycerol concentration was <1.0% (w/v). Osmometry was an accurate method for estimating residual glycerol concentration. Refractometry overestimated the residual glycerol concentration due to the interference from hemoglobin. However, when supernatant hemoglobin values were measured and used in the calculation for glycerol concentration, refractometry accurately estimated the residual glycerol concentration. The residual glycerol concentration of cryopreserved, deglycerolized CPD/SAGM RBCs can be accurately estimated using the supernatant refractive index and an equation that accounts for the supernatant hemoglobin concentration.

Sickle Cell Disease

MedlinePlus

... there is a problem with your hemoglobin. Hemoglobin is a protein in red blood cells that carries oxygen throughout the body. With ... Because of this, you may not have enough red blood cells. This is a condition called anemia, and it can make ...

Nanobiotechnological modification of hemoglobin and enzymes from this laboratory

PubMed Central

Chang, Thomas Ming Swi

2012-01-01

Polyhemoglobin is formed by the nanobiotechnological assembling of hemoglobin molecules into soluble nanodimension complex. A further step involves the nanobiotechnological assembly of hemoglobin, catalase and superoxide dismutase into a soluble nanodimension complex. This acts both as oxygen carrier and antioxidant to prevent the oxidative effects of hemoglobin. A further step is the preparation of nanodimension artificial red blood cells that contain hemoglobin and all the enzymes present in red blood cells. Other approaches include a polyhemoglobin–fibrinogen that acts as an oxygen carrier with platelet-like activity, and a polyhemoglobin–tyrosinase to retard the growth of a fatal skin cancer, melanoma. PMID:18565337

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.

Pseudosickling of hemoglobin Setif.

PubMed

Charache, S; Raik, E; Holtzclaw, D; Hathaway, P J; Powell, E; Fleming, P

1987-07-01

Hemoglobin Setif produces pseudosickling of red cells in vitro; the nature of the process and the conditions that "trigger" it are unknown. Studies of red cells, hemolysates, purified hemoglobin solutions, and artificial mixtures of Hb A and Setif suggest that pseudosickling is produced by intracellular crystallization of insoluble hemoglobin. Increased tonicity of the suspending medium accentuates the process, probably by causing a rise in intracellular hemoglobin concentration. If precipitates from A/Setif mixtures are analyzed, they always contain Hb A, suggesting an unusual mechanism for the process. Despite the fact that osmolality in the renal medulla is similar to that which produces pseudosickling in vitro, carriers do not have renal dysfunction of the type found in patients with sickle cell disease.

Thalassemia

MedlinePlus

... disorder that affects the way the body makes hemoglobin. Hemoglobin is the part of red blood cells that ... alpha globin and beta globin; these proteins make hemoglobin. In thalassemia, a gene that makes these proteins ...

Research opportunities in loss of red blood cell mass in space flight

NASA Technical Reports Server (NTRS)

Talbot, J. M.; Fisher, K. D.

1985-01-01

Decreases of red blood cell mass and plasma volume have been observed consistently following manned space flights. Losses of red cell mass by United States astronauts have averaged 10 to 15% (range: 2 to 21%). Based on postflight estimates of total hemoglobin, Soviet cosmonauts engaged in space missions lasting from 1 to 7 months have exhibited somewhat greater losses. Restoration of red cell mass requires from 4 to 6 weeks following return to Earth, regardless of the duration of space flight.

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 ...

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.

21 CFR 866.5470 - Hemoglobin immunological test system.

Code of Federal Regulations, 2011 CFR

2011-04-01

... hemoglobin (the oxygen-carrying pigment in red blood cells) in blood, urine, plasma, or other body fluids... Hemoglobin immunological test system. (a) Indentification. A hemoglobin immunological test system is a device... blood cells), and leukemia (cancer of the blood-forming organs). (b) Classification. Class II...

21 CFR 866.5470 - Hemoglobin immunological test system.

Code of Federal Regulations, 2013 CFR

2013-04-01

... hemoglobin (the oxygen-carrying pigment in red blood cells) in blood, urine, plasma, or other body fluids... Hemoglobin immunological test system. (a) Indentification. A hemoglobin immunological test system is a device... blood cells), and leukemia (cancer of the blood-forming organs). (b) Classification. Class II...

21 CFR 866.5470 - Hemoglobin immunological test system.

Code of Federal Regulations, 2012 CFR

2012-04-01

... hemoglobin (the oxygen-carrying pigment in red blood cells) in blood, urine, plasma, or other body fluids... Hemoglobin immunological test system. (a) Indentification. A hemoglobin immunological test system is a device... blood cells), and leukemia (cancer of the blood-forming organs). (b) Classification. Class II...

21 CFR 866.5470 - Hemoglobin immunological test system.

Code of Federal Regulations, 2014 CFR

2014-04-01

... hemoglobin (the oxygen-carrying pigment in red blood cells) in blood, urine, plasma, or other body fluids... Hemoglobin immunological test system. (a) Indentification. A hemoglobin immunological test system is a device... blood cells), and leukemia (cancer of the blood-forming organs). (b) Classification. Class II...

Dynamic regulation of erythropoiesis: A computer model of general applicability

NASA Technical Reports Server (NTRS)

Leonard, J. I.

1979-01-01

A mathematical model for the control of erythropoiesis was developed based on the balance between oxygen supply and demand at a renal oxygen detector which controls erythropoietin release and red cell production. Feedback regulation of tissue oxygen tension is accomplished by adjustments of hemoglobin levels resulting from the output of a renal-bone marrow controller. Special consideration was given to the determinants of tissue oxygenation including evaluation of the influence of blood flow, capillary diffusivity, oxygen uptake and oxygen-hemoglobin affinity. A theoretical analysis of the overall control system is presented. Computer simulations of altitude hypoxia, red cell infusion hyperoxia, and homolytic anemia demonstrate validity of the model for general human application in health and disease.

Prenatal Care: First Trimester Visits

MedlinePlus

... your baby's father is Rh positive. Measure your hemoglobin. Hemoglobin is an iron-rich protein found in red ... lungs so that it can be exhaled. Low hemoglobin is a sign of anemia — a lack of ...

A systems analysis of the erythropoietic responses to weightlessness. Volume 2: Description of the model of erythropoiesis regulation. Part A: Model for regulation of erythropoiesis. Part B: Detailed description of the model for regulation of erythropoiesis

NASA Technical Reports Server (NTRS)

Leonard, J. I.

1985-01-01

A mathematical model of the erythropoiesis on total red blood cell mass is presented. The loss of red cell mass has been a consistent finding during space flight. Computer simulation of this phenomenon required a model that could account for oxygen transport, red cell production, and red cell destruction. The elements incorporated into the feedback regulation loop of the model are based on the accepted concept that erythrocyte production is governed by the balance between oxygen supply and demand in the body. The mechanisms and pathways of the control circuit include oxygenation of hemoglobin and oxygenation of tissues by blood transport and diffusional processes. Other features of the model include a variable oxygen-hemoglobin affinity, and time delays which represent time for erythropoietin (erythrocyte-stimulating hormone) distribution in plasma, and time for maturation of the erythrocytes in bone marrow.

Sickle Cell Disease and Your Baby

MedlinePlus

... of SCD are: Sickle cell anemia (also called hemoglobin SS). Hemoglobin is the part of red blood cells that ... one sickle cell gene change from each parent. Hemoglobin SC. This condition is caused when a baby ...

Self-Monitoring Artificial Red Cells with Sufficient Oxygen Supply for Enhanced Photodynamic Therapy

NASA Astrophysics Data System (ADS)

Luo, Zhenyu; Zheng, Mingbin; Zhao, Pengfei; Chen, Ze; Siu, Fungming; Gong, Ping; Gao, Guanhui; Sheng, Zonghai; Zheng, Cuifang; Ma, Yifan; Cai, Lintao

2016-03-01

Photodynamic therapy has been increasingly applied in clinical cancer treatments. However, native hypoxic tumoural microenvironment and lacking oxygen supply are the major barriers hindering photodynamic reactions. To solve this problem, we have developed biomimetic artificial red cells by loading complexes of oxygen-carrier (hemoglobin) and photosensitizer (indocyanine green) for boosted photodynamic strategy. Such nanosystem provides a coupling structure with stable self-oxygen supply and acting as an ideal fluorescent/photoacoustic imaging probe, dynamically monitoring the nanoparticle biodistribution and the treatment of PDT. Upon exposure to near-infrared laser, the remote-triggered photosensitizer generates massive cytotoxic reactive oxygen species (ROS) with sufficient oxygen supply. Importantly, hemoglobin is simultaneously oxidized into the more active and resident ferryl-hemoglobin leading to persistent cytotoxicity. ROS and ferryl-hemoglobin synergistically trigger the oxidative damage of xenograft tumour resulting in complete suppression. The artificial red cells with self-monitoring and boosted photodynamic efficacy could serve as a versatile theranostic platform.

21 CFR 864.8165 - Calibrator for hemoglobin or hematocrit measurement.

Code of Federal Regulations, 2011 CFR

2011-04-01

... hemoglobin or hematocrit measurement is a device that approximates whole blood, red blood cells, or a hemoglobin derivative and that is used to set instruments intended to measure hemoglobin, the hematocrit, or both. It is a material whose characteristics have been precisely and accurately determined. (b...

21 CFR 864.8165 - Calibrator for hemoglobin or hematocrit measurement.

Code of Federal Regulations, 2010 CFR

2010-04-01

... hemoglobin or hematocrit measurement is a device that approximates whole blood, red blood cells, or a hemoglobin derivative and that is used to set instruments intended to measure hemoglobin, the hematocrit, or both. It is a material whose characteristics have been precisely and accurately determined. (b...

21 CFR 864.8165 - Calibrator for hemoglobin or hematocrit measurement.

Code of Federal Regulations, 2014 CFR

2014-04-01

... hemoglobin or hematocrit measurement is a device that approximates whole blood, red blood cells, or a hemoglobin derivative and that is used to set instruments intended to measure hemoglobin, the hematocrit, or both. It is a material whose characteristics have been precisely and accurately determined. (b...

21 CFR 864.8165 - Calibrator for hemoglobin or hematocrit measurement.

Code of Federal Regulations, 2013 CFR

2013-04-01

... hemoglobin or hematocrit measurement is a device that approximates whole blood, red blood cells, or a hemoglobin derivative and that is used to set instruments intended to measure hemoglobin, the hematocrit, or both. It is a material whose characteristics have been precisely and accurately determined. (b...

21 CFR 864.8165 - Calibrator for hemoglobin or hematocrit measurement.

Code of Federal Regulations, 2012 CFR

2012-04-01

... hemoglobin or hematocrit measurement is a device that approximates whole blood, red blood cells, or a hemoglobin derivative and that is used to set instruments intended to measure hemoglobin, the hematocrit, or both. It is a material whose characteristics have been precisely and accurately determined. (b...

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.

Molecular dynamics simulations indicate that deoxyhemoglobin, oxyhemoglobin, carboxyhemoglobin, and glycated hemoglobin under compression and shear exhibit an anisotropic mechanical behavior.

PubMed

Yesudasan, Sumith; Wang, Xianqiao; Averett, Rodney D

2018-05-01

We developed a new mechanical model for determining the compression and shear mechanical behavior of four different hemoglobin structures. Previous studies on hemoglobin structures have focused primarily on overall mechanical behavior; however, this study investigates the mechanical behavior of hemoglobin, a major constituent of red blood cells, using steered molecular dynamics (SMD) simulations to obtain anisotropic mechanical behavior under compression and shear loading conditions. Four different configurations of hemoglobin molecules were considered: deoxyhemoglobin (deoxyHb), oxyhemoglobin (HbO 2 ), carboxyhemoglobin (HbCO), and glycated hemoglobin (HbA 1C ). The SMD simulations were performed on the hemoglobin variants to estimate their unidirectional stiffness and shear stiffness. Although hemoglobin is structurally denoted as a globular protein due to its spherical shape and secondary structure, our simulation results show a significant variation in the mechanical strength in different directions (anisotropy) and also a strength variation among the four different hemoglobin configurations studied. The glycated hemoglobin molecule possesses an overall higher compressive mechanical stiffness and shear stiffness when compared to deoxyhemoglobin, oxyhemoglobin, and carboxyhemoglobin molecules. Further results from the models indicate that the hemoglobin structures studied possess a soft outer shell and a stiff core based on stiffness.

[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.

76 FR 51041 - Hemoglobin Standards and Maintaining Adequate Iron Stores in Blood Donors; Public Workshop

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-17

... Donors.'' The purpose of this public workshop is to discuss blood donor hemoglobin and hematocrit... that prospective blood donors, particularly women, are deferred. Allogeneic donors of a unit of red blood cells generally may not donate more than once in an 8 week period to ensure recovery of their red...

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.

21 CFR 864.8625 - Hematology quality control mixture.

Code of Federal Regulations, 2011 CFR

2011-04-01

... parameters such as white cell count (WBC), red cell count (RBC), platelet count (PLT), hemoglobin, hematocrit (HCT), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC). (b) Classification. Class II (performance standards). [45 FR 60637, Sept. 12...

Relationship between serum 25-hydroxyvitamin D and red blood cell indices in German adolescents.

PubMed

Doudin, Asmma; Becker, Andreas; Rothenberger, Aribert; Meyer, Thomas

2018-04-01

Since the impact of vitamin D on red blood cell formation has not been well studied, we aimed at assessing the putative link between serum 25-hydroxyvitamin D (25[OH]D) concentrations and hematological markers of erythropoiesis in a large cohort of German adolescents aged 11 to 17 years. In total, 5066 participants from the population-based, nationally representative KiGGS study (Kinder- und Jugendgesundheitssurvey, German Health Interview and Examination Survey for Children and Adolescents) were grouped into either tertiles or clinically accepted cutoff levels for serum 25(OH)D. Results demonstrated significant and inverse correlations between 25(OH)D levels and several hematological parameters including hemoglobin concentration (r = - 0.04, p = 0.003), mean corpuscular hemoglobin (r = - 0.11, p < 0.001), red blood cell count (r = - 0.04, p = 0.002), and soluble transferrin receptor (r = - 0.1, p < 0.001), whereas, in contrast, serum 25(OH)D was positively correlated to the mean corpuscular volume of erythrocytes (r = 0.08, p < 0.001). Multinomial regression models adjusted for clinically relevant confounders confirmed statistically significant differences between the two strata of 25(OH)D groups with respect to red blood cell markers (hemoglobin concentration, red blood cell count, mean corpuscular volume, and corpuscular hemoglobin, as well as iron and soluble transferrin receptor). The link between serum 25(OH)D and several important hematological parameters may point to an inhibitory role of vitamin D in the regulation of erythropoiesis in adolescents. What is Known: • The physiological effects of vitamin D on calcium homeostasis and bone metabolism have been established. • However, much less is known about the impact of circulating vitamin D on erythropoiesis. What is New: • Data from the KiGGS study in German adolescents demonstrated significant associations between serum vitamin D concentrations and red blood cell indices. • Further studies should be conducted to decipher the underlying mechanisms of vitamin D on erythropoiesis.

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).

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.

Hemoglobin (image)

MedlinePlus

... oxygen. In the lungs, oxygen is exchanged for carbon dioxide. Abnormalities of an individual's hemoglobin value can indicate defects in the normal balance between red blood cell production and destruction. Both ...

A Comparison of Red Cell Rejuvenation versus Mechanical Washing for the Prevention of Transfusion-associated Organ Injury in Swine.

PubMed

Woźniak, Marcin J; Qureshi, Saqib; Sullo, Nikol; Dott, William; Cardigan, Rebecca; Wiltshire, Michael; Nath, Mintu; Patel, Nishith N; Kumar, Tracy; Goodall, Alison H; Murphy, Gavin J

2018-02-01

We evaluated the effects of two interventions that modify the red cell storage lesion on kidney and lung injury in experimental models of transfusion. White-landrace pigs (n = 32) were allocated to receive sham transfusion (crystalloid), 14-day stored allogeneic red cells, 14-day red cells washed using the red cells washing/salvage system (CATS; Fresenius, Germany), or 14-day red cells rejuvenated using the inosine solution (Rejuvesol solution; Zimmer Biomet, USA) and washed using the CATS device. Functional, biochemical, and histologic markers of organ injury were assessed for up to 24 h posttransfusion. Transfusion of 14 day red cells resulted in lung injury (lung injury score vs. sham, mean difference -0.3 (95% CI, -0.6 to -0.1; P = 0.02), pulmonary endothelial dysfunction, and tissue leukocyte sequestration. Mechanical washing reduced red cell-derived microvesicles but increased cell-free hemoglobin in 14-day red cell units. Transfusion of washed red cells reduced leukocyte sequestration but did not reduce the lung injury score (mean difference -0.2; 95% CI, -0.5 to 0.1; P = 0.19) relative to 14-day cells. Transfusion of washed red cells also increased endothelial activation and kidney injury. Rejuvenation restored adenosine triphosphate to that of fresh red cells and reduced microvesicle concentrations without increasing cell-free hemoglobin release. Transfusion of rejuvenated red cells reduced plasma cell-free hemoglobin, leukocyte sequestration, and endothelial dysfunction in recipients and reduced lung and kidney injury relative to 14-day or washed 14-day cells. Reversal of the red cell storage lesion by rejuvenation reduces transfusion-associated organ injury in swine.

Assessment of changes in plasma hemoglobin and potassium levels in red cell units during processing and storage.

PubMed

Saini, Nishant; Basu, Sabita; Kaur, Ravneet; Kaur, Jasbinder

2015-06-01

Red cell units undergo changes during storage and processing. The study was planned to assess plasma potassium, plasma hemoglobin, percentage hemolysis during storage and to determine the effects of outdoor blood collection and processing on those parameters. Blood collection in three types of blood storage bags was done - single CPDA bag (40 outdoor and 40 in-house collection), triple CPD + SAGM bag (40 in-house collection) and quadruple CPD + SAGM bag with integral leukoreduction filter (40 in-house collection). All bags were sampled on day 0 (day of collection), day 1 (after processing), day 7, day 14 and day 28 for measurement of percentage hemolysis and potassium levels in the plasma of bag contents. There was significant increase in percentage hemolysis, plasma hemoglobin and plasma potassium level in all the groups during storage (p < 0.001). No significant difference was found between any parameter analyzed for outdoor and in-house collected single CPDA red cell units. There was significant lower percentage hemolysis (p < 0.001) and potassium (day 7 to day 14 - p < 0.05 and day 14 to day 28 - p < 0.001) in red cell units from day 7 onward until day 28 of storage in the leukoreduced quadruple bag as compared to the triple bag. The in-house single CPDA red cell units showed significantly more hemolysis (p < 0.001) as compared to the triple bags with SAGM additive solution after 28 days of storage. There is gradual increase in plasma hemoglobin and plasma potassium levels during the storage of red blood cells. Blood collection can be safely undertaken in outdoor blood donation camps even in hot summer months in monitored blood transport boxes. SAGM additive solution decreases the red cell hemolysis and allows extended storage of red cells. Prestorage leukoreduction decreases the red cell hemolysis and improves the quality of blood. Copyright © 2015 Elsevier Ltd. All rights reserved.

[Hemoglobin oxygen transport capacity in surgical endotoxicosis ].

PubMed

Poryadin, G V; Vlasov, A P; Trofimov, V A; Vlasova, T I; Kamkina, O V; Grigoryev, A G; Vlasov, P A

2016-01-01

In surgical endointoxication hemoglobin oxygen transport capacity of red blood cells (hemoglobin affinity ligands: the ability to bind and release ligands) is reduced and is associated with the severity of endogenous intoxication. Violation of oxygen transport function of hemoglobin at endogenous intoxication is associated with conformational changes of a biomolecule, and its possible influence on reactive oxygen species, which confirmed in experiments in vitro: under the influence of oxygen-iron ascorbate ability of hemoglobin deteriorates. Largely similar structural and functional changes in hemoglobin occur in patients with surgical endotoxicosis.

Anemia and Iron Deficiency in Vietnamese Children, 6 to 11 Years Old.

PubMed

Le Nguyen Bao, Khanh; Tran Thuy, Nga; Nguyen Huu, Chinh; Khouw, Ilse; Deurenberg, Paul

2016-07-01

In a population sample of 385 children, 6 to 11 years old, venous blood parameters-hemoglobin (Hb), ferritin, red blood cell count (RBC), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), C-reactive protein (CRP), and α1-acid glycoprotein (AGP)-were determined to get insight into the iron status. The prevalence of anemia was 11.4%; 5.6% had iron deficiency (ID), whereas 0.4% had ID anemia. Correction for inflammation based on CRP and AGP did not markedly change the overall prevalence of ID and ID anemia. Stunted children had lower Hb and ferritin values compared with nonstunted children, and thin children had lower values compared with normal-weight or overweight and obese children. Many nonanemic children had alert values for RBC, MCV, MCH, and MCHC. It is concluded that although the prevalence of anemia is of the magnitude of a mild public health problem, the iron status of many nonanemic children is borderline, as indicated by a high number of children with low values for red blood cytology. © 2016 APJPH.

Red cell volume with changes in plasma osmolarity during maximal exercise.

NASA Technical Reports Server (NTRS)

Van Beaumont, W.

1973-01-01

The volume of the red cell in vivo was measured during acute changes in plasma osmolarity evoked through short (6 to 8 min) maximal exercise in six male volunteer subjects. Simultaneous measurements of mean corpuscular red cell volume (MCV), hematocrit, blood hemoglobin, mean corpuscular hemoglobin concentration (MCHC), and plasma osmolarity showed that there was no change in the MCV or MCHC with a concomitant rise of nearly 6% in plasma osmolarity. Apparently, in vivo, the volume of the red cell in exercising healthy human subjects does not change measurably, in spite of significant changes in osmotic pressure of the surrounding medium. Consequently, it is not justified to correct postexercise hematocrit measurements for changes in plasma osmolarity.

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.

Contrast enhancement for in vivo visible reflectance imaging of tissue oxygenation.

PubMed

Crane, Nicole J; Schultz, Zachary D; Levin, Ira W

2007-08-01

Results are presented illustrating a straightforward algorithm to be used for real-time monitoring of oxygenation levels in blood cells and tissue based on the visible spectrum of hemoglobin. Absorbance images obtained from the visible reflection of white light through separate red and blue bandpass filters recorded by monochrome charge-coupled devices (CCDs) are combined to create enhanced images that suggest a quantitative correlation between the degree of oxygenated and deoxygenated hemoglobin in red blood cells. The filter bandpass regions are chosen specifically to mimic the color response of commercial 3-CCD cameras, representative of detectors with which the operating room laparoscopic tower systems are equipped. Adaptation of this filter approach is demonstrated for laparoscopic donor nephrectomies in which images are analyzed in terms of real-time in vivo monitoring of tissue oxygenation.

Combinatorial Screening Of Inorganic And Organometallic Materials

DOEpatents

Li, Yi , Li, Jing , Britton, Ted W.

2002-06-25

A method for differentiating and enumerating nucleated red blood cells in a blood sample is described. The method includes the steps of lysing red blood cells of a blood sample with a lytic reagent, measuring nucleated blood cells by DC impedance measurement in a non-focused flow aperture, differentiating nucleated red blood cells from other cell types, and reporting nucleated red blood cells in the blood sample. The method further includes subtracting nucleated red blood cells and other interference materials from the count of remaining blood cells, and reporting a corrected white blood cell count of the blood sample. Additionally, the method further includes measuring spectrophotometric absorbance of the sample mixture at a predetermined wavelength of a hemoglobin chromogen formed upon lysing the blood sample, and reporting hemoglobin concentration of the blood sample.

User's instructions for the erythropoiesis regulatory model

NASA Technical Reports Server (NTRS)

1978-01-01

The purpose of the model provides a method to analyze some of the events that could account for the decrease in red cell mass observed in crewmen returning from space missions. The model is based on the premise that erythrocyte production is governed by the balance between oxygen supply and demand at a renal sensing site. Oxygen supply is taken to be a function of arterial oxygen tension, mean corpuscular hemoglobin concentration, oxy-hemoglobin carrying capacity, hematocrit, and blood flow. Erythrocyte destruction is based on the law of mass action. The instantaneous hematocrit value is derived by integrating changes in production and destruction rates and accounting for the degree of plasma dilution.

Hemoglobin electrophoresis

MedlinePlus

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

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.

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

Five-coordinate H64Q neuroglobin as a ligand-trap antidote for carbon monoxide poisoning

PubMed Central

Azarov, Ivan; Wang, Ling; Rose, Jason J.; Xu, Qinzi; Huang, Xueyin N.; Belanger, Andrea; Wang, Ying; Guo, Lanping; Liu, Chen; Ucer, Kamil B.; McTiernan, Charles F.; O’Donnell, Christopher P.; Shiva, Sruti; Tejero, Jesús; Kim-Shapiro, Daniel B.; Gladwin, Mark T.

2016-01-01

Carbon monoxide (CO) is a leading cause of poisoning deaths worldwide, with no available antidotal therapy. We introduce a potential treatment paradigm for CO poisoning, based on near-irreversible binding of CO by an engineered human neuroglobin (Ngb). Ngb is a six-coordinate hemoprotein, with the heme iron coordinated by two histidine residues. We mutated the distal histidine to glutamine (H64Q) and substituted three surface cysteines with less reactive amino acids to form a five-coordinate heme protein (Ngb-H64Q-CCC). This molecule exhibited an unusually high affinity for gaseous ligands, with a P50 value for oxygen of 0.015 mmHg. Ngb-H64Q-CCC bound CO about 500 times more strongly than did hemoglobin. Incubation of Ngb-H64Q-CCC with 100% CO-saturated hemoglobin, either cell-free or encapsulated in human red blood cells, reduced the half-life of carboxy-hemoglobin to 0.11 and 0.41 minutes, respectively, from a value that is ≥ 200 minutes when the hemoglobin or cells are only exposed to air. Infusions of Ngb-H64Q-CCC to CO-poisoned mice enhanced CO removal from red blood cells, restored heart rate and blood pressure, increased survival, and were followed by rapid renal elimination of CO-bound Ngb-H64Q-CCC. Heme-based scavenger molecules with very high CO binding affinity such as our mutant five-coordinate Ngb are potential antidotes for CO poisoning by virtue of their ability to bind and eliminate CO. PMID:27928027

In vivo imaging of tissue scattering parameter and cerebral hemodynamics in rat brain with a digital red-green-blue camera

NASA Astrophysics Data System (ADS)

Nishidate, Izumi; Mustari, Afrina; Kawauchi, Satoko; Sato, Shunichi; Sato, Manabu; Kokubo, Yasuaki

2017-02-01

We propose a rapid imaging method to monitor the spatial distribution of total hemoglobin concentration (CHbT), the tissue oxygen saturation, and the scattering power b in the expression of μs'=aλ-b as the scattering parameters in cerebral cortex using a digital red-green-blue camera. In the method, the RGB-values are converted into the tristimulus values in CIEXYZ color space which is compatible with the common RGB working spaces. Monte Carlo simulation (MCS) for light transport in tissue is used to specify a relation among the tristimulus XYZ-values and the concentration of oxygenated hemoglobin, that of deoxygenated hemoglobin, and the scattering power b. In the present study, we performed sequential recordings of RGB images of in vivo exposed rat brain during the cortical spreading depolarization evoked by the topical application of KCl. Changes in the total hemoglobin concentration and the tissue oxygen saturation imply the temporary change in cerebral blood flow during CSD. Decrease in the scattering power b was observed before the profound increase in the total hemoglobin concentration, which is indicative of the reversible morphological changes in brain tissue during CSD. The results in this study indicate potential of the method to evaluate the pathophysiological conditions in brain tissue with a digital red-green-blue camera.

Toward laboratory blood test-comparable photometric assessments for anemia in veterinary hematology

NASA Astrophysics Data System (ADS)

Kim, Taehoon; Choi, Seung Ho; Lambert-Cheatham, Nathan; Xu, Zhengbin; Kritchevsky, Janice E.; Bertin, Francois-René; Kim, Young L.

2016-10-01

Anemia associated with intestinal parasites and malnutrition is the leading cause of morbidity and mortality in small ruminants worldwide. Qualitative scoring of conjunctival redness has been developed so that farmers can gauge anemia in sheep and goats to identify animals that require treatment. For clinically relevant anemia diagnosis, complete blood count-comparable quantitative methods often rely on complicated and expensive optical instruments, requiring detailed spectral information of hemoglobin. We report experimental and numerical results for simple, yet reliable, noninvasive hemoglobin detection that can be correlated with laboratory-based blood hemoglobin testing for anemia diagnosis. In our pilot animal study using calves, we exploit the third eyelid (i.e., palpebral conjunctiva) as an effective sensing site. To further test spectrometer-free (or spectrometerless) hemoglobin assessments, we implement full spectral reconstruction from RGB data and partial least square regression. The unique combination of RGB-based spectral reconstruction and partial least square regression could potentially offer uncomplicated instrumentation and avoid the use of a spectrometer, which is vital for realizing a compact and inexpensive hematology device for quantitative anemia detection in the farm field.

Toward laboratory blood test-comparable photometric assessments for anemia in veterinary hematology.

PubMed

Kim, Taehoon; Choi, Seung Ho; Lambert-Cheatham, Nathan; Xu, Zhengbin; Kritchevsky, Janice E; Bertin, Francois-René; Kim, Young L

2016-10-01

Anemia associated with intestinal parasites and malnutrition is the leading cause of morbidity and mortality in small ruminants worldwide. Qualitative scoring of conjunctival redness has been developed so that farmers can gauge anemia in sheep and goats to identify animals that require treatment. For clinically relevant anemia diagnosis, complete blood count-comparable quantitative methods often rely on complicated and expensive optical instruments, requiring detailed spectral information of hemoglobin. We report experimental and numerical results for simple, yet reliable, noninvasive hemoglobin detection that can be correlated with laboratory-based blood hemoglobin testing for anemia diagnosis. In our pilot animal study using calves, we exploit the third eyelid (i.e., palpebral conjunctiva) as an effective sensing site. To further test spectrometer-free (or spectrometerless) hemoglobin assessments, we implement full spectral reconstruction from RGB data and partial least square regression. The unique combination of RGB-based spectral reconstruction and partial least square regression could potentially offer uncomplicated instrumentation and avoid the use of a spectrometer, which is vital for realizing a compact and inexpensive hematology device for quantitative anemia detection in the farm field.

Human induced pluripotent stem cells can reach complete terminal maturation: in vivo and in vitro evidence in the erythropoietic differentiation model

PubMed Central

Kobari, Ladan; Yates, Frank; Oudrhiri, Noufissa; Francina, Alain; Kiger, Laurent; Mazurier, Christelle; Rouzbeh, Shaghayegh; El-Nemer, Wassim; Hebert, Nicolas; Giarratana, Marie-Catherine; François, Sabine; Chapel, Alain; Lapillonne, Hélène; Luton, Dominique; Bennaceur-Griscelli, Annelise; Douay, Luc

2012-01-01

Background Human induced pluripotent stem cells offer perspectives for cell therapy and research models for diseases. We applied this approach to the normal and pathological erythroid differentiation model by establishing induced pluripotent stem cells from normal and homozygous sickle cell disease donors. Design and Methods We addressed the question as to whether these cells can reach complete erythroid terminal maturation notably with a complete switch from fetal to adult hemoglobin. Sickle cell disease induced pluripotent stem cells were differentiated in vitro into red blood cells and characterized for their terminal maturation in terms of hemoglobin content, oxygen transport capacity, deformability, sickling and adherence. Nucleated erythroblast populations generated from normal and pathological induced pluripotent stem cells were then injected into non-obese diabetic severe combined immunodeficiency mice to follow the in vivo hemoglobin maturation. Results We observed that in vitro erythroid differentiation results in predominance of fetal hemoglobin which rescues the functionality of red blood cells in the pathological model of sickle cell disease. We observed, in vivo, the switch from fetal to adult hemoglobin after infusion of nucleated erythroid precursors derived from either normal or pathological induced pluripotent stem cells into mice. Conclusions These results demonstrate that human induced pluripotent stem cells: i) can achieve complete terminal erythroid maturation, in vitro in terms of nucleus expulsion and in vivo in terms of hemoglobin maturation; and ii) open the way to generation of functionally corrected red blood cells from sickle cell disease induced pluripotent stem cells, without any genetic modification or drug treatment. PMID:22733021

Aloe emodin, an anthroquinone from Aloe vera acts as an anti aggregatory agent to the thermally aggregated hemoglobin

NASA Astrophysics Data System (ADS)

Furkan, Mohammad; Alam, Md Tauqir; Rizvi, Asim; Khan, Kashan; Ali, Abad; Shamsuzzaman; Naeem, Aabgeena

2017-05-01

Aggregation of proteins is a physiological process which contributes to the pathophysiology of several maladies including diabetes mellitus, Huntington's and Alzheimer's disease. In this study we have reported that aloe emodin (AE), an anthroquinone, which is one of the active components of the Aloe vera plant, acts as an inhibitor of hemoglobin (Hb) aggregation. Hb was thermally aggregated at 60 °C for four days as evident by increased thioflavin T and ANS fluorescence, shifted congo red absorbance, appearance of β sheet structure, increase in turbidity and presence of oligomeric aggregates. Increasing concentration of AE partially reverses the aggregation of the model heme protein (hemoglobin). The maximum effect of AE was observed at 100 μM followed by saturation at 125 μM. The results were confirmed by UV-visible spectrometry, intrinsic fluorescence, ThT, ANS, congo red assay as well as transmission electron microscopy (TEM). These results were also supported by fourier transform infrared spectroscopy (FTIR) and circular dichroism (CD) which shows the disappearance of β sheet structure and appearance of α helices. This study will serve as baseline for translatory research and the development of AE based therapeutics for diseases attributed to protein aggregation.

Effect of Red Light-Emitting Diodes Irradiation on Hemoglobin for Potential Hypertension Treatment Based on Confocal Micro-Raman Spectroscopy.

PubMed

Qiu, Xuejun; Huang, Hanchuan; Huang, Zhitong; Zhuang, Zhengfei; Guo, Zhouyi; Liu, Songhao

2017-01-01

Red light-emitting diodes (LED) were used to irradiate the isolated hypertension hemoglobin (Hb) and Raman spectra difference was recorded using confocal micro-Raman spectroscopy. Differences were observed between the controlled and irradiated Hb by comparing the spectra records. The Raman spectrum at the 1399 cm -1 band decreased following prolonged LED irradiation. The intensity of the 1639 cm -1 band decreased dramatically in the first five minutes and then gradually increased in a time-dependent manner. This observation indicated that LED irradiation increased the ability of oxygen binding in Hb. The appearance of the heme aggregation band at 1399 cm -1 , in addition to the oxygen marker band at 1639 cm -1 , indicated that, in our study, 30 min of irradiation with 15.0 mW was suitable for inhibiting heme aggregation and enhancing the oxygen-carrying capacity of Hb. Principal component analysis showed a one-to-one relationship between irradiated Hb at different time points and the corresponding Raman spectra. Our approach could be used to analyze the hemoglobin from patients with confocal micro-Raman spectroscopy and is helpful for developing new nondrug hypertension therapy.

Development of Liposome Encapsulated Hemoglobin (LEH) and Studies of Hemorrhagic Shock by Use of Imaging Studies with Oxygen-15 and Other Radiotracers

DTIC Science & Technology

2004-09-01

hemoglobin in the oxy-hemoglobin state [Stratton 1988; Takeoka 1997]. 3) Decreased Vasoactivity. Because LEH has physical properties closer to red cells...in rabbit arterial segments. J Appl Physiol 82:1826-1835. [21] Sakai H, Horinouchi H, Masada Y, Takeoka S, Ikeda E, Takaori M, Kobayashi K and...4317-4325. [22] Sakai H, Horinouchi H, Tomiyama K, Ikeda E, Takeoka S, Kobayashi K and Tsuchida E (2001) Hemoglobin-vesicles as oxygen carriers

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.

Augmentation of oxygen transport by various hemoglobins as determined by pulsed field gradient NMR.

PubMed

Budhiraja, Vikas; Hellums, J David; Post, Jan F M

2002-11-01

Diffusion of oxyhemoglobin has been shown to augment the oxygen transport inside the red blood cells. Measurement of hemoglobin diffusion coefficients by pulsed-field gradient (PFG) nuclear magnetic resonance (NMR) technique can be used for estimating this augmentation effect. Self-diffusion coefficients of polymerized and unpolymerized bovine hemoglobin (Hb) and several other proteins were measured using this technique. The Hb diffusion coefficient was used to determine the effective permeability of oxygen and augmentation of oxygen transport through samples of Hb solutions due to diffusion of oxyhemoglobin. The values compared well with our previous diffusion cell measurements of effective diffusivity and augmentation. Our NMR studies show that even at low concentrations the augmentation of oxygen transport due to diffusion can be significant. The PFG NMR technique can thus provide an accurate and easy method for measuring augmentation of oxygen transport, especially in dilute samples of Hb. The results on polyhemoglobin and high-molecular-weight hemoglobin are of both basic interest and practical value in assessing the promise and performance of hemoglobin-based blood substitutes.

Association between red blood cell indices and CD4 count in HIV-positive reproductive women

NASA Astrophysics Data System (ADS)

Lumbanraja, S. N.; Siregar, D. I. S.

2018-03-01

Red blood cell indices, hemoglobin, and hematocrit reflect rapidity of HIV disease progression. This study aims to determine red blood cell indices and CD4 count in HIV-positive reproductive women. This study was a cross sectional study conducted at AIDS outpatient clinic at Haji Adam Malik General Hospital, Medan Indonesia. All seropositive reproductive women within antiretroviral therapy consented for blood count and CD4 examination. Data were collected and analyzed with SPSS 19. In subjects with CD4≤350 mm3, mean hemoglobin was 10.95 ± 2.01, hematocrit was 31.83 ± 5.04%, MCV was 84.17 ± 11.41, MCH was 25.98 ± 2.65, and MCHC was 32.18 ± 2.17. Mean hemoglobin, hematocrit, and MCH value was significantly lower in subjects with CD4 ≤350 mm3 (p=0.014; p=0.001; p=0.01; respectively). Lower Hb, Ht, and MCH associated with thelower CD4 count.

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

Method for determining properties of red blood cells

DOEpatents

Gourley, Paul L.

2001-01-01

A method for quantifying the concentration of hemoglobin in a cell, and indicia of anemia, comprises determining the wavelength of the longitudinal mode of a liquid in a laser microcavity; determining the wavelength of the fundamental transverse mode of a red blood cell in the liquid in the laser microcavity; and determining if the cell is anemic from the difference between the wavelength of the longitudinal mode and the fundamental transverse mode. In addition to measuring hemoglobin, the invention includes a method using intracavity laser spectroscopy to measure the change in spectra as a function of time for measuring the influx of water into a red blood cell and the cell's subsequent rupture.

[Susceptibility of induced sickle in samples of heterozygous hemoglobin S patients (sickle cell trait) suffering diabetes mellitus type 2].

PubMed

Díaz-Piedra, Pablo; Cervantes-Villagrana, Alberto Rafael; Ramos-Jiménez, Raúl; Presno-Bernal, José Miguel; Cervantes-Villagrana, Rodolfo Daniel

2015-01-01

Hemoglobin S is an abnormal protein that induces morphological changes in erythrocyte in low-oxygen conditions. In Mexico, it is reported that up to 13.7% of the population with mutation in one allele are considered asymptomatic (sickle cell trait). The sickle cell trait and diabetes mellitus are conditions that occur together in more than one million patients worldwide. Both diseases possibly produce microvascular changes in retinopathy and acute chest syndrome. The aim of this study was to evaluate the induction of sickle cells in samples of diabetic patients with sickle cell trait to identify altered red cell parameters. We obtained samples of diabetic patients to determine hemoglobin A1c and S; furthermore, red blood cell biometrics data were analyzed. We found that older men with diabetes were susceptible to generate sickle cells and this correlated with reduced red blood cell count and an increase in media cell volume. In samples of women diabetes, there were no differences. We conclude that samples from patients with sickle cell trait and diabetes can cause sickle cells with high frequency in men, with lower red blood cells count and increased mean corpuscular volume as susceptibility parameters.

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.

[Establishment and validation of a neonatal pig model of hemolytic jaundice].

PubMed

Li, Yong-Fu; Ma, Yue-Lan; Nie, Ling; Chen, Shuan; Jin, Mei-Fang; Wang, San-Lan

2016-05-01

To establish a neonatal pig model of hemolytic jaundice. Twelve seven-day-old purebred Yorkshire pigs were randomly divided into an experimental group and a control group (n=6 each). Immunization of New Zealand white rabbits was used to prepare rabbit anti-porcine red blood cell antibodies, and rabbit anti-porcine red blood cell serum was separated. The neonatal pigs in the experimental group were given an intravenous injection of rabbit anti-porcine red blood cell serum (5 mL), and those in the control group were given an intravenous injection of normal saline (5 mL). Venous blood samples were collected every 6 hours for routine blood test and liver function evaluation. The experimental group had a significantly higher serum bilirubin level than the control group at 18 hours after the injection of rabbit anti-porcine red blood cell serum (64±30 μmol/L vs 20±4 μmol/L; P<0.05). In the experimental group, the serum bilirubin level reached the peak at 48 hours (275±31 μmol/L), and decreased significantly at 96 hours after the injection (95±17 μmol/L), but all significantly higher than that in the control group (P<0.05). At 18 hours after the injection, the experimental group had a significantly lower red blood cell (RBC) count than the control group [(4.58±0.32)×10(12)/L vs (5.09±0.44)×10(12)/L; P<0.05]; at 24 hours, the experimental group showed further reductions in RBC count and hemoglobin level and had significantly lower RBC count and hemoglobin level than the control group [RBC: (4.21±0.24)×10(12)/L vs (5.11±0.39)×10(12)/L, P<0.05; hemoglobin: 87±3 g vs 97±6 g, P<0.05]. The differences in RBC count and hemoglobin level between the two groups were largest at 36-48 hours. The neonatal pig model of hemolytic jaundice simulates the pathological process of human hemolytic jaundice well and provides good biological and material bases for further investigation of neonatal hemolysis.

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

Evidence by chromatography and mass spectrometry that inorganic nitrite induces S-glutathionylation of hemoglobin in human red blood cells.

PubMed

Böhmer, Anke; Pich, Andreas; Schmidt, Mario; Haghikia, Arash; Tsikas, Dimitrios

2016-04-15

Previously we found by HPLC with fluorescence detection that inorganic nitrite induces oxidation of glutathione (GSH) to its disulfide (GSSG) in intact and more abundantly in lyzed red blood cells (RBCs) from healthy humans. In the present work, we performed MS-based protein analysis and observed that nitrite (range, 0-20mM) induces formation of S-glutathionyl hemoglobin (HbSSG) at cysteine (Cys) β93 and β112 of oxyhemoglobin (HbO2) in lyzed human RBCs (range, 6-8mM HbO2). Hemoglobin species were isolated from incubation mixtures of nitrite in lyzed RBCs by ultrafiltration or affinity chromatography and analyzed by HPLC and LC-MS/MS. The mechanism likely involves inhibition of catalase activity by nitrite (IC50, 9 μM), which allows H2O2 to accumulate and oxidize Cys moieties of oxyhemoglobin and erythrocytic GSH to form HbSSG in addition to GSSG. In freshly prepared hemolysate samples, nitrite induced release of superoxide and molecular oxygen. In the presence of paracetamol and nitrite in hemolysate samples, 3-nitro-paracetamol was detected. Nitrite also induced S-nitroso hemoglobin (HbSNO) formation in low yield (i.e., 0.1%). Synthetic cysteine (Cys), glutathione (GSH), N-acetylcysteine (NAC) and N-acetylcysteine ethyl ester (NACET) inhibited nitrite-induced modifications of oxyhemoglobin including methemoglobin, HbSSG (CysSH > NACET > GSH ≈ NAC; thiol concentration, 50 μM) and HbSNO. Nitrite-induced oxidative modifications may alter physiological hemoglobin functions and may require alternative treatments for conditions associated with oxidized hemoglobin like in nitrite-induced methemoglobinemia. Accumulation of soluble Cys in RBCs via oral administration of NACET could be a new promising strategy to prevent nitrite-induced methemoglobinemia by nitrite and other oxidants. Copyright © 2016 Elsevier B.V. All rights reserved.

Transfusion of Packed Red Blood Cells--The Indications Have Changed.

PubMed

Cook, Alan; Miller, Nate

2015-12-01

Whole blood/packed red blood cells (pRBC) units transfused in the U.S. totaled 13,785,000 in 2011. A single institution in South Dakota transfused 6,485 units of pRBC in 2013. Current thresholds for transfusion have changed and each transfusion has the risk of causing an adverse reaction; thus, it is important to ensure pRBCs are administered appropriately. Due to these changes and the potential risks associated with transfusion, we reviewed the literature regarding appropriate indications for transfusion of pRBC. Our review specifically focused on four disease entities: iron-deficiency anemia, acute upper gastrointestinal (GI) bleeding, acute coronary syndromes, and chronic ischemic heart disease. Based on our findings, we recommend utilizing an overall conservative approach to the transfusion of pRBC. In patients with iron-deficiency anemia, first try alternative methods to improve hemoglobin levels; in those with acute GI bleeding, transfuse for hemoglobin less than 7 g/dL; in patients with acute coronary syndromes, let symptoms/signs be your guide; and in patients with ischemic heart disease, transfuse for hemoglobin levels less than 8 g/dL or if they are symptomatic. Most importantly, be cautious to not fixate on numbers alone; always incorporate patients' symptoms and co-morbidities when considering whether to transfuse pRBCs.

Blood doping and its detection.

PubMed

Jelkmann, Wolfgang; Lundby, Carsten

2011-09-01

Hemoglobin mass is a key factor for maximal exercise capacity. Some athletes apply prohibited techniques and substances with intent to increase hemoglobin mass and physical performance, and this is often difficult to prove directly. Autologous red blood cell transfusion cannot be traced on reinfusion, and also recombinant erythropoietic proteins are detectable only within a certain timeframe. Novel erythropoietic substances, such as mimetics of erythropoietin (Epo) and activators of the Epo gene, may soon enter the sports scene. In addition, Epo gene transfer maneuvers are imaginable. Effective since December 2009, the World Anti-Doping Agency has therefore implemented "Athlete Biologic Passport Operating Guidelines," which are based on the monitoring of several parameters for mature red blood cells and reticulocytes. Blood doping may be assumed, when these parameters change in a nonphysiologic way. Hematologists should be familiar with blood doping practices as they may play an important role in evaluating blood profiles of athletes with respect to manipulations, as contrasted with the established diagnosis of clinical disorders and genetic variations.

The Chronic and Acute Effects of Exercise Upon Selected Blood Measures.

ERIC Educational Resources Information Center

Roitman, J. L.; Brewer, J. P.

This study investigated the effects of chronic and acute exercise upon selected blood measures and indices. Nine male cross-country runners were studied. Red blood count, hemoglobin, and hematocrit were measured using standard laboratory techniques; mean corpuscular volume (MCV), mean corpuscular hemoglobin, and mean corpuscular hemoglobin…

Automatic detection and segmentation of vascular structures in dermoscopy images using a novel vesselness measure based on pixel redness and tubularness

NASA Astrophysics Data System (ADS)

Kharazmi, Pegah; Lui, Harvey; Stoecker, William V.; Lee, Tim

2015-03-01

Vascular structures are one of the most important features in the diagnosis and assessment of skin disorders. The presence and clinical appearance of vascular structures in skin lesions is a discriminating factor among different skin diseases. In this paper, we address the problem of segmentation of vascular patterns in dermoscopy images. Our proposed method is composed of three parts. First, based on biological properties of human skin, we decompose the skin to melanin and hemoglobin component using independent component analysis of skin color images. The relative quantities and pure color densities of each component were then estimated. Subsequently, we obtain three reference vectors of the mean RGB values for normal skin, pigmented skin and blood vessels from the hemoglobin component by averaging over 100000 pixels of each group outlined by an expert. Based on the Euclidean distance thresholding, we generate a mask image that extracts the red regions of the skin. Finally, Frangi measure was applied to the extracted red areas to segment the tubular structures. Finally, Otsu's thresholding was applied to segment the vascular structures and get a binary vessel mask image. The algorithm was implemented on a set of 50 dermoscopy images. In order to evaluate the performance of our method, we have artificially extended some of the existing vessels in our dermoscopy data set and evaluated the performance of the algorithm to segment the newly added vessel pixels. A sensitivity of 95% and specificity of 87% were achieved.

Oxygen transport in blood at high altitude: role of the hemoglobin-oxygen affinity and impact of the phenomena related to hemoglobin allosterism and red cell function.

PubMed

Samaja, Michele; Crespi, Tiziano; Guazzi, Marco; Vandegriff, Kim D

2003-10-01

Altitude hypoxia is a major challenge to the blood O2 transport system, and adjustments of the blood-O2 affinity might contribute significantly to hypoxia adaptation. In principle, lowering the blood-O2 affinity is advantageous because it lowers the circulatory load required to assure adequate tissue oxygenation up to a threshold corresponding to about 5,000 m altitude, whereas at higher altitudes an increased blood-O2 affinity appears more advantageous. However, the rather contradictory experimental evidence raises the question whether other factors superimpose on the apparent changes of the blood-O2 affinity. The most important of these are as follows: (1) absolute temperature and temperature gradients within the body; (2) the intracapillary Bohr effect; (3) the red cell population heterogeneity in terms of O2 affinity; (4) control of altitude alkalosis; (5) the possible role of hemoglobin as a carrier of the vasodilator nitric oxide; (6) the effect of varied red cell transit times through the capillaries.

In vivo imaging of scattering and absorption properties of exposed brain using a digital red-green-blue camera

NASA Astrophysics Data System (ADS)

Nishidate, Izumi; Yoshida, Keiichiro; Kawauchi, Satoko; Sato, Shunichi; Sato, Manabu

2014-03-01

We investigate a method to estimate the spectral images of reduced scattering coefficients and the absorption coefficients of in vivo exposed brain tissues in the range from visible to near-infrared wavelength (500-760 nm) based on diffuse reflectance spectroscopy using a digital RGB camera. In the proposed method, the multi-spectral reflectance images of in vivo exposed brain are reconstructed from the digital red, green blue images using the Wiener estimation algorithm. The Monte Carlo simulation-based multiple regression analysis for the absorbance spectra is then used to specify the absorption and scattering parameters of brain tissue. In this analysis, the concentration of oxygenated hemoglobin and that of deoxygenated hemoglobin are estimated as the absorption parameters whereas the scattering amplitude a and the scattering power b in the expression of μs'=aλ-b as the scattering parameters, respectively. The spectra of absorption and reduced scattering coefficients are reconstructed from the absorption and scattering parameters, and finally, the spectral images of absorption and reduced scattering coefficients are estimated. The estimated images of absorption coefficients were dominated by the spectral characteristics of hemoglobin. The estimated spectral images of reduced scattering coefficients showed a broad scattering spectrum, exhibiting larger magnitude at shorter wavelengths, corresponding to the typical spectrum of brain tissue published in the literature. In vivo experiments with exposed brain of rats during CSD confirmed the possibility of the method to evaluate both hemodynamics and changes in tissue morphology due to electrical depolarization.

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.

Effect of red blood cells on the growth of Porphyromonas endodontalis and microbial community development.

PubMed

Zerr, M A; Cox, C D; Johnson, W T; Drake, D R

1998-04-01

Establishment of a microbial community in the root canal system depends on numerous factors, of which nutrient availability may be one of the most important. We hypothesized that the presence of red blood cells or hemoglobin in this environment could cause shifts in microbial composition of communities, resulting in organisms such as Porphyromonas endodontalis becoming more dominant. An in vitro model system using mixed, batch cultures was performed with the bacteria P. endodontalis, Fusobacterium nucleatum, Peptostreptococcus micros and Campylobacter rectus. Bacteria were cultured in media with or without the addition of washed red blood cells, hemoglobin, or serum. Cyclic growth studies revealed that P. endodontalis was lost from the community of organisms after three cycles. However, inclusion of red blood cells resulted in establishment of this organism. Moreover, red blood cells added to pure cultures of P. endodontalis substantially enhanced growth and protected the organisms from oxygen. We conclude that the presence of red blood cells could result in shifts of microbial communities of organisms within the root canal system.

Effects of Aged Stored Autologous Red Blood Cells on Human Endothelial Function

PubMed Central

Kanias, Tamir; Triulzi, Darrel; Donadee, Chenell; Barge, Suchitra; Badlam, Jessica; Jain, Shilpa; Belanger, Andrea M.; Kim-Shapiro, Daniel B.

2015-01-01

Rationale: A major abnormality that characterizes the red cell “storage lesion” is increased hemolysis and reduced red cell lifespan after infusion. Low levels of intravascular hemolysis after transfusion of aged stored red cells disrupt nitric oxide (NO) bioavailabity, via accelerated NO scavenging reaction with cell-free plasma hemoglobin. The degree of intravascular hemolysis post-transfusion and effects on endothelial-dependent vasodilation responses to acetylcholine have not been fully characterized in humans. Objectives: To evaluate the effects of blood aged to the limits of Food and Drug Administration–approved storage time on the human microcirculation and endothelial function. Methods: Eighteen healthy individuals donated 1 U of leukopheresed red cells, divided and autologously transfused into the forearm brachial artery 5 and 42 days after blood donation. Blood samples were obtained from stored blood bag supernatants and the antecubital vein of the infusion arm. Forearm blood flow measurements were performed using strain-gauge plethysmography during transfusion, followed by testing of endothelium-dependent blood flow with increasing doses of intraarterial acetylcholine. Measurements and Main Results: We demonstrate that aged stored blood has higher levels of arginase-1 and cell-free plasma hemoglobin. Compared with 5-day blood, the transfusion of 42-day packed red cells decreases acetylcholine-dependent forearm blood flows. Intravascular venous levels of arginase-1 and cell-free plasma hemoglobin increase immediately after red cell transfusion, with more significant increases observed after infusion of 42-day-old blood. Conclusions: We demonstrate that the transfusion of blood at the limits of Food and Drug Administration–approved storage has a significant effect on the forearm circulation and impairs endothelial function. Clinical trial registered with www.clinicaltrials.gov (NCT 01137656) PMID:26222884

Effect of hemoglobin polymerization on oxygen transport in hemoglobin solutions.

PubMed

Budhiraja, Vikas; Hellums, J David

2002-09-01

The effect of hemoglobin (Hb) polymerization on facilitated transport of oxygen in a bovine hemoglobin-based oxygen carrier was studied using a diffusion cell. In high oxygen tension gradient experiments (HOTG) at 37 degrees C the diffusion of dissolved oxygen in polymerized Hb samples was similar to that in unpolymerized Hb solutions during oxygen uptake. However, in the oxygen release experiments, the transport by diffusion of dissolved oxygen was augmented by diffusion of oxyhemoglobin over a range of oxygen saturations. The augmentation was up to 30% in the case of polymerized Hb and up to 100% in the case of unpolymerized Hb solution. In experiments performed at constant, low oxygen tension gradients in the range of physiological significance, the augmentation effect was less than that in the HOTG experiments. Oxygen transport in polymerized Hb samples was approximately the same as that in unpolymerized samples over a wide range of oxygen tensions. However, at oxygen tensions lower than 30 mm Hg, there were more significant augmentation effects in unpolymerized bovine Hb samples than in polymerized Hb. The results presented here are the first accurate, quantitative measurements of effective diffusion coefficients for oxygen transport in hemoglobin-based oxygen carriers of the type being evaluated to replace red cells in transfusions. In all cases the oxygen carrier was found to have higher effective oxygen diffusion coefficients than blood.

Genetic modulation of sickle cell anemia

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

Steinberg, M.H.

1995-05-01

Sickle cell anemia, a common disorder associated with reduced life span of the red blood cell and vasoocclusive events, is caused by a mutation in the {Beta}-hemoglobin gene. Yet, despite this genetic homogeneity, the phenotype of the disease is heterogeneous. This suggests the modulating influence of associated inherited traits. Some of these may influence the accumulation of fetal hemoglobin, a hemoglobin type that interferes with the polymerization of sickle hemoglobin. Another inherited trait determines the accumulation of {alpha}-globin chains. This review focuses on potential genetic regulators of the phenotype of sickle cell anemia. 125 refs., 6 figs., 3 tabs.

Cloned Hemoglobin Genes Enhance Growth Of Cells

NASA Technical Reports Server (NTRS)

Khosla, Chaitan; Bailey, James E.

1991-01-01

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

OSMOTIC PROPERTIES OF HUMAN RED CELLS.

PubMed

SAVITZ, D; SIDEL, V W; SOLOMON, A K

1964-09-01

The hematocrit method as a technique for determining red cell volume under anisotonic conditions has been reexamined and has been shown, with appropriate corrections for trapped plasma, to provide a true measure of cell volume. Cell volume changes in response to equilibration in anisotonic media were found to be much less than those predicted for an ideal osmometer; this anomalous behavior cannot be explained by solute leakage or by the changing osmotic coefficient of hemoglobin, but is quantitatively accounted for by the hypothesis that 20 per cent of intracellular water is bound to hemoglobin and is unavailable for participation in osmotic shifts.

The nature of multiphoton fluorescence from red blood cells

NASA Astrophysics Data System (ADS)

Saytashev, Ilyas; Murphy, Michael; Osseiran, Sam; Spence, Dana M.; Evans, Conor L.; Dantus, Marcos

2016-03-01

We report on the nature of multiphoton excited fluorescence observed from human erythrocytes (red blood cells RBC's) and their "ghosts" following 800nm sub-15 fs excitation. The detected optical signal is assigned as two-photon excited fluorescence from hemoglobin. Our findings are supported by wavelength-resolved fluorescence lifetime decay measurements using time-correlated single photon counting system from RBC's, their ghosts as well as in vitro samples of various fluorophores including riboflavin, NADH, NAD(P)H, hemoglobin. We find that low-energy and short-duration pulses allow two-photon imaging of RBC's, but longer more intense pulses lead to their destruction.

Direct sGC Activation Bypasses NO Scavenging Reactions of Intravascular Free Oxy-Hemoglobin and Limits Vasoconstriction

PubMed Central

Tabima, D. Marcela; Specht, Patricia A.C.; Tejero, Jesús; Champion, Hunter C.; Kim-Shapiro, Daniel B.; Baust, Jeff; Mik, Egbert G.; Hildesheim, Mariana; Stasch, Johannes-Peter; Becker, Eva-Maria; Truebel, Hubert

2013-01-01

Abstract Aims: Hemoglobin-based oxygen carriers (HBOC) provide a potential alternative to red blood cell (RBC) transfusion. Their clinical application has been limited by adverse effects, in large part thought to be mediated by the intravascular scavenging of the vasodilator nitric oxide (NO) by cell-free plasma oxy-hemoglobin. Free hemoglobin may also cause endothelial dysfunction and platelet activation in hemolytic diseases and after transfusion of aged stored RBCs. The new soluble guanylate cyclase (sGC) stimulator Bay 41-8543 and sGC activator Bay 60-2770 directly modulate sGC, independent of NO bioavailability, providing a potential therapeutic mechanism to bypass hemoglobin-mediated NO inactivation. Results: Infusions of human hemoglobin solutions and the HBOC Oxyglobin into rats produced a severe hypertensive response, even at low plasma heme concentrations approaching 10 μM. These reactions were only observed for ferrous oxy-hemoglobin and not analogs that do not rapidly scavenge NO. Infusions of L-NG-Nitroarginine methyl ester (L-NAME), a competitive NO synthase inhibitor, after hemoglobin infusion did not produce additive vasoconstriction, suggesting that vasoconstriction is related to scavenging of vascular NO. Open-chest hemodynamic studies confirmed that hypertension occurred secondary to direct effects on increasing vascular resistance, with limited negative cardiac inotropic effects. Intravascular hemoglobin reduced the vasodilatory potency of sodium nitroprusside (SNP) and sildenafil, but had no effect on vasodilatation by direct NO-independent activation of sGC by BAY 41-8543 and BAY 60-2770. Innovation and Conclusion: These data suggest that both sGC stimulators and sGC activators could be used to restore cyclic guanosine monophosphate-dependent vasodilation in conditions where cell-free plasma hemoglobin is sufficient to inhibit endogenous NO signaling. Antioxid. Redox Signal. 19, 2232–2243. PMID:23697678

Transfusions and blood loss in total hip and knee arthroplasty: a prospective observational study.

PubMed

Carling, Malin S; Jeppsson, Anders; Eriksson, Bengt I; Brisby, Helena

2015-03-28

There is a high prevalence of blood product transfusions in orthopedic surgery. The reported prevalence of red blood cell transfusions in unselected patients undergoing hip or knee replacement varies between 21% and 70%. We determined current blood loss and transfusion prevalence in total hip and knee arthroplasty when tranexamic acid was used as a routine prophylaxis, and further investigated potential predictors for excessive blood loss and transfusion requirement. In total, 193 consecutive patients undergoing unilateral hip (n = 114) or knee arthroplasty (n = 79) were included in a prospective observational study. Estimated perioperative blood loss was calculated and transfusions of allogeneic blood products registered and related to patient characteristics and perioperative variables. Overall transfusion rate was 16% (18% in hip patients and 11% in knee patients, p = 0.19). Median estimated blood loss was significantly higher in hip patients (984 vs 789 mL, p < 0.001). Preoperative hemoglobin concentration was the only independent predictor of red blood cell transfusion in hip patients while low hemoglobin concentration, body mass index, and operation time were independent predictors for red blood cell transfusion in knee patients. The prevalence of red blood cell transfusion was lower than previously reported in unselected total hip or knee arthroplasty patients. Routine use of tranexamic acid may have contributed. Low preoperative hemoglobin levels, low body mass index, and long operation increase the risk for red blood cell transfusion.

Hemoglobin Dynamics in Red Blood Cells: Correlation to Body Temperature

PubMed Central

Stadler, A. M.; Digel, I.; Artmann, G. M.; Embs, J. P.; Zaccai, G.; Büldt, G.

2008-01-01

A transition in hemoglobin behavior at close to body temperature has been discovered recently by micropipette aspiration experiments on single red blood cells (RBCs) and circular dichroism spectroscopy on hemoglobin solutions. The transition temperature was directly correlated to the body temperatures of a variety of species. In an exploration of the molecular basis for the transition, we present neutron scattering measurements of the temperature dependence of hemoglobin dynamics in whole human RBCs in vivo. The data reveal a change in the geometry of internal protein motions at 36.9°C, at human body temperature. Above that temperature, amino acid side-chain motions occupy larger volumes than expected from normal temperature dependence, indicating partial unfolding of the protein. Global protein diffusion in RBCs was also measured and the findings compared favorably with theoretical predictions for short-time self-diffusion of noncharged hard-sphere colloids. The results demonstrated that changes in molecular dynamics in the picosecond time range and angstrom length scale might well be connected to a macroscopic effect on whole RBCs that occurs at body temperature. PMID:18708462

Hemoglobin dynamics in red blood cells: correlation to body temperature.

PubMed

Stadler, A M; Digel, I; Artmann, G M; Embs, J P; Zaccai, G; Büldt, G

2008-12-01

A transition in hemoglobin behavior at close to body temperature has been discovered recently by micropipette aspiration experiments on single red blood cells (RBCs) and circular dichroism spectroscopy on hemoglobin solutions. The transition temperature was directly correlated to the body temperatures of a variety of species. In an exploration of the molecular basis for the transition, we present neutron scattering measurements of the temperature dependence of hemoglobin dynamics in whole human RBCs in vivo. The data reveal a change in the geometry of internal protein motions at 36.9 degrees C, at human body temperature. Above that temperature, amino acid side-chain motions occupy larger volumes than expected from normal temperature dependence, indicating partial unfolding of the protein. Global protein diffusion in RBCs was also measured and the findings compared favorably with theoretical predictions for short-time self-diffusion of noncharged hard-sphere colloids. The results demonstrated that changes in molecular dynamics in the picosecond time range and angstrom length scale might well be connected to a macroscopic effect on whole RBCs that occurs at body temperature.

[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.

[Optimization of trehalose loading in red blood cells before freeze-drying].

PubMed

Zhuang, Yuan; Liu, Jing-Han; Ouyang, Xi-Lin; Chen, Lin-Feng; Che, Ji

2007-04-01

The key points for better protection of trehalose in freeze-drying red blood cells (RBCs) are to resolve non-osmosis of trehalose to red blood cells and to make cytoplasmic trehalose to reach effective concentration. This study was aimed to investigate the regularity of loading RBCs with trehalose, screen out optimal loading condition and evaluate the effect of trehalose on physico-chemical parameters of RBCs during the period of loading. The cytoplasmic trehalose concentration in red blood cells, free hemoglobin and ATP level were determined at different incubation temperatures (4, 22 and 37 degrees C), different trehaolse concentrations (0, 200, 400, 600, 800 and 1000 mmol/L) and different incubation times (2, 4, 6, 8 and 10 hours), the cytoplasmic trehalose, free hemoglobin (FHb), hemoglobin (Hb) and mean corpuscular volume (MCV) in fresh RBCs and RBCs stored for 72 hours at 4 degrees C were compared, when loading condition was ensured. The results showed that with increase of incubation temperature, time and extracellular trehalose concentration, the loading of trehalose in RBCs also increased. Under the optimal loading condition, cytoplasmic trehalose concentration and free hemoglobin level of fresh RBCs and RBCs stored for 72 hours at 4 degrees C were 65.505 +/- 6.314 mmol/L, 66.2 +/- 5.002 mmol/L and 6.567 +/- 2.568 g/L, 16.168 +/- 3.922 g/L respectively. It is concluded that the most optimal condition of loading trehalose is that fresh RBCs incubate in 800 mmol/L trehalose solution for 8 hours at 37 degrees C. This condition can result in a efficient cytoplasmic trehalose concentration. The study provides an important basis for long-term preservation of RBCs.

Relative deformability of red blood cells in sickle cell trait and sickle cell anemia by trapping and dragging

NASA Astrophysics Data System (ADS)

Solomon, Rance; Cooper, James; Welker, Gabriel; Aguilar, Elaura; Flanagan, Brooke; Pennycuff, Chelsey; Scott, David; Farone, Anthony; Farone, Mary; Erenso, Daniel; Mushi, Robert; del Pilar Aguinaga, Maria

2013-06-01

Genetic mutation of the β-globin gene or inheritance of this mutated gene changes the chemical composition of the oxygen-carrying hemoglobin molecule that could lead to either the heterozygote genotype, resulting in sickle cell trait (SCT), or the homozygote genotype, resulting in sickle cell anemia (SCA). These mutations could affect the reversible elastic deformations of the red blood cells (RBCs) which are vital for biological functions. We have investigated this effect by studying the differences in the deformability of RBCs from blood samples of an individual with SCT and an untreated patient with SCA along with hemoglobin quantitation of each blood sample. Infrared 1064 nm laser trap force along with drag shear force are used to induce deformation in the RBCs. Ultra2-High Performance Liquid Chromatography (UHPLC) is used for the hemoglobin quantitation.

Blood indicators of seasonal metabolic patterns in captive adult gray wolves

USGS Publications Warehouse

Seal, U.S.; Mech, L.D.

1983-01-01

Blood samples and physical data were collected weekly from a colony of gray wolves (Canis lupus) maintained under natural weather arid light conditions. Sampling over 33 continuous months indicated that hemoglobin, hematocrit, red blood cells, mean corpuscular hemoglobin concentration (MCHC), and thyroxine exhibited consistent circannual patterns of variation in both males and females. Hemoglobin levels peaked at 15-16 g/dl in January in females and at 16-17 g/dl in February in males, and were lowest in August at 10.5-11.5 g/dl (P < 0.00001). The cyclic patterns of hematocrit, red blood cells, and MCHC were similarly timed. Females also had a cyclic pattern of white blood cell counts and body weight; their weight peaked in early February and was lowest in August (P < 0.001). Body temperature, urea nitrogen, mean corpuscular volume (MCV), serum glucose, and cortisol did not follow a consistent seasonal pattern.

Raman spectroscopic monitoring of the bioeffects of nitroglycerin on Hb-O II in single red blood cell

NASA Astrophysics Data System (ADS)

Chiang, Huihua Kenny; Ruan, Hung-Shiang; Cheng, Hung-You; Fang, Tung-Ting

2007-02-01

Raman spectroscopy has been shown to have the potential for providing oxygenated ability of erythrocytes. Raman line at 1638 cm-1 has also been reported as one significant oxygenic indicator for erythrocytes. In this research, we develop the Raman spectroscopic monitoring of the bioeffects of Nitroglycerin on hemoglobin oxygen saturation in a single red blood cell (RBC). Nitroglycerin has been frequently used in the management of angina pectoris. Nitroglycerin liberates nitric oxide (NO) to blood vessels. NO is an oxidizer that easily converts hemoglobin to methemoglobin. The conversion may cause the decrease of oxygenated ability of erythrocytes. In this study, we observed the oxidize state of erythrocytes caused by the over dosage of Nitroglycerin. When the dose of Nitroglycerin exceeds 2x10 -4 M, the oxygenic state of erythrocytes decreases significantly. The Raman spectroscopic results demonstrate the observation of the bioeffects of Nitroglycerin on hemoglobin.

What befalls the proteins and water in a living cell when the cell dies?

PubMed

Ling, Gilbert N; Fu, Ya-zhen

2005-01-01

The solvency of solutes of varying molecular size in the intracellular water of freshly-killed Ehrlich carcinoma cells fits the same theoretical curve that describes the solvency of similar solutes in a 36% solution of native bovine hemoglobin--a protein found only in red blood cells and making up 97.3% of the red cell's total intracellular proteins. The merging of the two sets of data confirms the prediction of the AI Hypothesis that key intracellular protein(s) in dying cells undergo(es) a transition from: (1) one in which the polypeptide NHCO groups assume a fully-extended conformation with relatively strong power of polarizing and orienting the bulk-phase water in multilayers; to (2) one in which most of the polypeptide NHCO groups are engaged in alpha-helical and other "introvert" conformations (see below for definition) with much weaker power in polarizing-orienting multilayers of bulk-phase water. This concordance of the two sets of data also shows that what we now call native hemoglobin--supposedly denoting hemoglobin found in its natural state in living red blood cells--, in fact, more closely resembles the water-polarizing, and -orienting intracellular proteins in dead cells. Although in the dead Ehrlich carcinoma cells as well as in the 36% solution of native hemoglobin, much of the protein's polypeptide NHCO groups are engaged in alpha-helical and other "introvert" conformation (Perutz 1969; Weissbluth 1974), both systems produce a weak but nonetheless pervasive and "long-range" water polarization and orientation. It is suggested that in both the dead Ehrlich carcinoma ascites cells and in the 36% native bovine hemoglobin solution, enough polypeptide NHCO groups assume the fully-extended conformation to produce the weak but far-reaching multilayer water polarization and orientation observed.

Structure and reactivity of hexacoordinate hemoglobins

PubMed Central

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

2015-01-01

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

Feasibility study of red blood cell debulking by magnetic field-flow fractionation with step-programmed flow

PubMed Central

Moore, Lee R.; Williams, P. Stephen; Nehl, Franziska; Abe, Koji; Chalmers, Jeffrey J.; Zborowski, Maciej

2013-01-01

Emerging applications of rare cell separation and analysis, such as separation of mature red blood cells from hematopoietic cell cultures require efficient methods of red blood cell (RBC) debulking. We have tested the feasibility of magnetic RBC separation as an alternative to centrifugal separation using an approach based on the mechanism of magnetic field-flow fractionation (MgFFF). A specially designed permanent magnet assembly generated a quadrupole field having a maximum field of 1.68 T at the magnet pole tips, zero field at the aperture axis, and a nearly constant radial field gradient of 1.75 T/mm (with a negligible angular component) inside a cylindrical aperture of 1.9 mm (diameter) and 76 mm (length). The cell samples included high-spin hemoglobin RBCs obtained by chemical conversion of hemoglobin to methemoglobin (met RBC) or by exposure to anoxic conditions (deoxy RBC), low-spin hemoglobin obtained by exposure of RBC suspension to ambient air (oxy RBC), and mixtures of deoxy RBC and cells from a KG-1a white blood cell (WBC) line. The observation that met RBCs did not elute from the channel at the lower flow rate of 0.05 mL/min applied for 15 min but quickly eluted at the subsequent higher flow rate of 2.0 mL/min was in agreement with FFF theory. The well-defined experimental conditions (precise field and flow characteristics) and a well-established FFF theory verified by studies with model cell systems provided us with a strong basis for making predictions about potential practical applications of the magnetic RBC separation. PMID:24141316

Mechanistic Modeling of Hemoglobin Glycation and Red Blood Cell Kinetics Enables Personalized Diabetes Monitoring

PubMed Central

Malka, Roy; Nathan, David M.; Higgins, John M.

2017-01-01

The glycated hemoglobin assay (HbA1c) is essential for the diagnosis and management of diabetes because it provides the best estimate of a patient’s average blood glucose (AG) over the preceding 2–3 months and is the best predictor of disease complications. However, there is substantial unexplained glucose-independent variation in HbA1c that makes AG estimation inaccurate and limits the precision of medical care for diabetics. The true AG of a non-diabetic and a poorly-controlled diabetic may differ by less than 15 mg/dL, but patients with identical HbA1c and thus identical HbA1c-based estimates of AG may have true AG that differs by more than 60 mg/dl. We combine a mechanistic mathematical model of hemoglobin glycation and red blood cell flux with large sets of intra-patient glucose measurements to derive patient-specific estimates of non-glycemic determinants of HbA1c including mean red blood cell age (MRBC). We find that interpatient variation in derived MRBC explains all glucose-independent variation in HbA1c. We then use our model to personalize prospective estimates of AG and reduce errors by more than 50% in four independent sets of more than 200 patients. The current standard of care provided AG estimates with errors > 15 mg/dL for 1 in 3 patients. Our patient-specific method reduced this error rate to 1 in 10. This personalized approach to estimating AG from HbA1c should improve medical care for diabetes using existing clinical measurements. PMID:27708063

Feasibility study of red blood cell debulking by magnetic field-flow fractionation with step-programmed flow.

PubMed

Moore, Lee R; Williams, P Stephen; Nehl, Franziska; Abe, Koji; Chalmers, Jeffrey J; Zborowski, Maciej

2014-02-01

Emerging applications of rare cell separation and analysis, such as separation of mature red blood cells from hematopoietic cell cultures, require efficient methods of red blood cell (RBC) debulking. We have tested the feasibility of magnetic RBC separation as an alternative to centrifugal separation using an approach based on the mechanism of magnetic field-flow fractionation (MgFFF). A specially designed permanent magnet assembly generated a quadrupole field having a maximum field of 1.68 T at the magnet pole tips, zero field at the aperture axis, and a nearly constant radial field gradient of 1.75 T/mm (with a negligible angular component) inside a cylindrical aperture of 1.9 mm (diameter) and 76 mm (length). The cell samples included high-spin hemoglobin RBCs obtained by chemical conversion of hemoglobin to methemoglobin (met RBC) or by exposure to anoxic conditions (deoxy RBC), low-spin hemoglobin obtained by exposure of RBC suspension to ambient air (oxy RBC), and mixtures of deoxy RBC and cells from a KG-1a white blood cell (WBC) line. The observation that met RBCs did not elute from the channel at the lower flow rate of 0.05 mL/min applied for 15 min but quickly eluted at the subsequent higher flow rate of 2.0 mL/min was in agreement with FFF theory. The well-defined experimental conditions (precise field and flow characteristics) and a well-established FFF theory verified by studies with model cell systems provided us with a strong basis for making predictions about potential practical applications of the magnetic RBC separation.

Red blood cell thickness is evolutionarily constrained by slow, hemoglobin-restricted diffusion in cytoplasm.

PubMed

Richardson, Sarah L; Swietach, Pawel

2016-10-25

During capillary transit, red blood cells (RBCs) must exchange large quantities of CO 2 and O 2 in typically less than one second, but the degree to which this is rate-limited by diffusion through cytoplasm is not known. Gas diffusivity is intuitively assumed to be fast and this would imply that the intracellular path-length, defined by RBC shape, is not a factor that could meaningfully compromise physiology. Here, we evaluated CO 2 diffusivity (D CO2 ) in RBCs and related our results to cell shape. D CO2 inside RBCs was determined by fluorescence imaging of [H + ] dynamics in cells under superfusion. This method is based on the principle that H + diffusion is facilitated by CO 2 /HCO 3 - buffer and thus provides a read-out of D CO2 . By imaging the spread of H + ions from a photochemically-activated source (6-nitroveratraldehyde), D CO2 in human RBCs was calculated to be only 5% of the rate in water. Measurements on RBCs containing different hemoglobin concentrations demonstrated a halving of D CO2 with every 75 g/L increase in mean corpuscular hemoglobin concentration (MCHC). Thus, to compensate for highly-restricted cytoplasmic diffusion, RBC thickness must be reduced as appropriate for its MCHC. This can explain the inverse relationship between MCHC and RBC thickness determined from >250 animal species.

Red blood cell thickness is evolutionarily constrained by slow, hemoglobin-restricted diffusion in cytoplasm

PubMed Central

Richardson, Sarah L.; Swietach, Pawel

2016-01-01

During capillary transit, red blood cells (RBCs) must exchange large quantities of CO2 and O2 in typically less than one second, but the degree to which this is rate-limited by diffusion through cytoplasm is not known. Gas diffusivity is intuitively assumed to be fast and this would imply that the intracellular path-length, defined by RBC shape, is not a factor that could meaningfully compromise physiology. Here, we evaluated CO2 diffusivity (DCO2) in RBCs and related our results to cell shape. DCO2 inside RBCs was determined by fluorescence imaging of [H+] dynamics in cells under superfusion. This method is based on the principle that H+ diffusion is facilitated by CO2/HCO3− buffer and thus provides a read-out of DCO2. By imaging the spread of H+ ions from a photochemically-activated source (6-nitroveratraldehyde), DCO2 in human RBCs was calculated to be only 5% of the rate in water. Measurements on RBCs containing different hemoglobin concentrations demonstrated a halving of DCO2 with every 75 g/L increase in mean corpuscular hemoglobin concentration (MCHC). Thus, to compensate for highly-restricted cytoplasmic diffusion, RBC thickness must be reduced as appropriate for its MCHC. This can explain the inverse relationship between MCHC and RBC thickness determined from >250 animal species. PMID:27777410

Knowledge and Attitude of Nigerian Adolescents to Premarital Genotying.

ERIC Educational Resources Information Center

Egbochuku, E. O.; Imogie, A. O.

Sickle cell disease (SCD) refers to a group of hereditary disorders of the structure of hemoglobin of red blood cells. This disorder involves the inheritance of two abnormal genes, which are related to the hemoglobin promotion, at least, one of which is the sickle cell gene. Nigeria, by virtue of her large population, has the greatest number of…

The measurement of hemoglobin oxygen saturation using multiwavelength photoacoustic microscopy

NASA Astrophysics Data System (ADS)

Deng, Zilin; Yang, Xiaoquan; Yu, Lejun; Gong, Hui

2010-02-01

Hemoglobin oxygen saturation (SO2) is one of the most critical functional parameters to the metabolism. In this paper, we mainly introduced some initial results of measuring blood oxygen using multi-wavelength photoacoustic microscopy (PAM). In phantom study, we demonstrate the photoacoustic signal amplitude increases linearly with the concentration of red or blue ink. Then the calculated concentration of red ink in double-ink mixtures with PAM has a 5% difference with the result measured with spectrophotometric analysis. In ex vivo experiment, the measured result exhibt 15% difference between the PAM and spectrophotometric analysis. Experiment results suggest that PAM could be used to determine the SO2 quantitatively.

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.

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.

Jaundice

MedlinePlus

... causes your skin and the whites of your eyes to turn yellow. Too much bilirubin causes jaundice. Bilirubin is a yellow chemical in hemoglobin, the substance that carries oxygen in your red blood cells. As red blood cells break down, your body builds new cells to replace them. The old ones are ...

Pseudoreticulocytosis in a patient with hemoglobin Köln due to autofluorescent erythrocytes enumerated as reticulocytes by the Cell-Dyn 4000.

PubMed

Sato, Shoko; Hirayama, Koichi; Koyama, Akio; Harano, Teruo; Nagasawa, Toshiro; Ninomiya, Haruhiko

2004-01-01

Pseudoreticulocytosis in a 25-year-old female patient with hemoglobin Köln is reported. The abnormal hemoglobin, hemoglobin Köln (beta chain, Val98-->Met), had previously been confirmed in the patient at the age of 21 years, as well as in her mother, by polymerase chain reaction-based direct sequence analysis of the beta globin gene. The patient underwent splenectomy at the age of 22 years. On her admission to our hospital for treatment of an immunoglobulin A nephropathy, an analysis by an automated hematology analyzer, the Abbott Cell-Dyn 4000 (CD4000), reported a marked reticulocytosis. Staining by the Brecher method with new methylene blue indicated a moderate reticulocytosis (5.7%) of a lesser extent than that indicated by the CD4000 (51.1%). The frequencies of red blood cells (RBC) with Pappenheimer bodies (13.8%), Heinz bodies (32.7%), and Howell-Jolly bodies (0.3%) were increased. The CD4000 detects RBC with RNA fluorescently stained with CD4K530 as reticulocytes. Autofluorescence of RBC with hemoglobin Köln, as we demonstrated by flow cytometry and fluorescent microscopy, was considered to have caused the pseudoreticulocytosis on the fully automated reticulocyte enumeration by the CD4000.

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.

21 CFR 866.5460 - Haptoglobin immunological test system.

Code of Federal Regulations, 2014 CFR

2014-04-01

... that binds hemoglobin, the oxygen-carrying pigment in red blood cells) in serum. Measurement of haptoglobin may aid in the diagnosis of hemolytic diseases (diseases in which the red blood cells rupture and... Haptoglobin immunological test system. (a) Identification. A haptoglobin immunological test system is a device...

21 CFR 866.5460 - Haptoglobin immunological test system.

Code of Federal Regulations, 2012 CFR

2012-04-01

... that binds hemoglobin, the oxygen-carrying pigment in red blood cells) in serum. Measurement of haptoglobin may aid in the diagnosis of hemolytic diseases (diseases in which the red blood cells rupture and... Haptoglobin immunological test system. (a) Identification. A haptoglobin immunological test system is a device...

21 CFR 866.5460 - Haptoglobin immunological test system.

Code of Federal Regulations, 2013 CFR

2013-04-01

... that binds hemoglobin, the oxygen-carrying pigment in red blood cells) in serum. Measurement of haptoglobin may aid in the diagnosis of hemolytic diseases (diseases in which the red blood cells rupture and... Haptoglobin immunological test system. (a) Identification. A haptoglobin immunological test system is a device...

21 CFR 866.5460 - Haptoglobin immunological test system.

Code of Federal Regulations, 2011 CFR

2011-04-01

... that binds hemoglobin, the oxygen-carrying pigment in red blood cells) in serum. Measurement of haptoglobin may aid in the diagnosis of hemolytic diseases (diseases in which the red blood cells rupture and... Haptoglobin immunological test system. (a) Identification. A haptoglobin immunological test system is a device...

Blood transfusion-acquired hemoglobin C.

PubMed

Suarez, A A; Polski, J M; Grossman, B J; Johnston, M F

1999-07-01

Unexpected and confusing laboratory test results can occur if a blood sample is inadvertently collected following a blood transfusion. A potential for transfusion-acquired hemoglobinopathy exists because heterozygous individuals show no significant abnormalities during the blood donor screening process. Such spurious results are infrequently reported in the medical literature. We report a case of hemoglobin C passively transferred during a red blood cell transfusion. The proper interpretation in our case was assisted by calculations comparing expected hemoglobin C concentration with the measured value. A review of the literature on transfusion-related preanalytic errors is provided.

[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.

Solid phase pegylation of hemoglobin.

PubMed

Suo, Xiaoyan; Zheng, Chunyang; Yu, Pengzhan; Lu, Xiuling; Ma, Guanghui; Su, Zhiguo

2009-01-01

A solid phase conjugation process was developed for attachment of polyethylene glycol to hemoglobin molecule. Bovine hemoglobin was loaded onto an ion exchange chromatography column and adsorbed by the solid medium. Succinimidyl carbonate mPEG was introduced in the mobile phase after the adsorption. Pegylation took place between the hemoglobin on the solid phase, and the pegylation reagent in the liquid phase. A further elution was carried out to separate the pegylated and the unpegylated protein. Analysis by HPSEC, SDS-PAGE, and MALLS demonstrated that the fractions eluted from the solid phase contained well-defined components. Pegylated hemoglobin with one PEG chain was obtained with the yield of 75%, in comparison to the yield of 30% in the liquid phase pegylation. The P(50) values of the mono-pegylated hemoglobin, prepared with SC-mPEG 5 kDa, 10 kDa and 20 kDa, were 19.97, 20.23 and 20.54 mmHg, which were much closer to the value of red blood cells than that of pegylated hemoglobin prepared with the conventional method.

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.

[The chemical action of gun powder gases on biological tissues in a point-blank shot].

PubMed

Popov, V L; Isakov, V D; Babakhanian, R V; Karnasevich, Iu A

1992-01-01

Chemical effect of gun powder gas on the biologic tissues manifests by red-brown staining of the tissues, mainly at the expense of methemoglobin and sulfhemoglobin. Scarlet staining of the tissues at the edges of gun-shot wounds is not a specific marker of a shot made from a short distance; it may emerge several hours after wounding at the expense of hydroxy-hemoglobin and is not at all related to the chemical effect of gun powder gas. The conditions conducive to scarlet staining are an open wound permitting free oxygenation by air oxygen and hemoglobin transfer from the injured red cells into blood plasma and adjacent tissues.

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.

The rate of the deoxygenation reaction limits myoglobin- and hemoglobin-facilitated O₂ diffusion in cells.

PubMed

Endeward, Volker

2012-05-01

A mathematical model describing facilitation of O(2) diffusion by the diffusion of myoglobin and hemoglobin is presented. The equations are solved numerically by a finite-difference method for the conditions as they prevail in cardiac and skeletal muscle and in red cells without major simplifications. It is demonstrated that, in the range of intracellular diffusion distances, the degree of facilitation is limited by the rate of the chemical reaction between myglobin or hemoglobin and O(2). The results are presented in the form of relationships between the degree of facilitation and the length of the diffusion path on the basis of the known kinetics of the oxygenation-deoxygenation reactions. It is concluded that the limitation by reaction kinetics reduces the maximally possible facilitated oxygen diffusion in cardiomyoctes by ∼50% and in skeletal muscle fibers by ∼ 20%. For human red blood cells, a reduction of facilitated O(2) diffusion by 36% is obtained in agreement with previous reports. This indicates that, especially in cardiomyocytes and red cells, chemical equilibrium between myoglobin or hemoglobin and O(2) is far from being established, an assumption that previously has often been made. Although the "O(2) transport function" of myoglobin in cardiac muscle cells thus is severely limited by the chemical reaction kinetics, and to a lesser extent also in skeletal muscle, it is noteworthy that the speed of release of O(2) from MbO(2), the "storage function," is not limited by the reaction kinetics under physiological conditions.

Red blood cells in sports: effects of exercise and training on oxygen supply by red blood cells

PubMed Central

Mairbäurl, Heimo

2013-01-01

During exercise the cardiovascular system has to warrant substrate supply to working muscle. The main function of red blood cells in exercise is the transport of O2 from the lungs to the tissues and the delivery of metabolically produced CO2 to the lungs for expiration. Hemoglobin also contributes to the blood's buffering capacity, and ATP and NO release from red blood cells contributes to vasodilation and improved blood flow to working muscle. These functions require adequate amounts of red blood cells in circulation. Trained athletes, particularly in endurance sports, have a decreased hematocrit, which is sometimes called “sports anemia.” This is not anemia in a clinical sense, because athletes have in fact an increased total mass of red blood cells and hemoglobin in circulation relative to sedentary individuals. The slight decrease in hematocrit by training is brought about by an increased plasma volume (PV). The mechanisms that increase total red blood cell mass by training are not understood fully. Despite stimulated erythropoiesis, exercise can decrease the red blood cell mass by intravascular hemolysis mainly of senescent red blood cells, which is caused by mechanical rupture when red blood cells pass through capillaries in contracting muscles, and by compression of red cells e.g., in foot soles during running or in hand palms in weightlifters. Together, these adjustments cause a decrease in the average age of the population of circulating red blood cells in trained athletes. These younger red cells are characterized by improved oxygen release and deformability, both of which also improve tissue oxygen supply during exercise. PMID:24273518

Role of hemolysis in red cell adenosine triphosphate release in simulated exercise conditions in vitro.

PubMed

Mairbäurl, Heimo; Ruppe, Florian A; Bärtsch, Peter

2013-10-01

Specific adenosine triphosphate (ATP) release from red blood cells has been discussed as a possible mediator controlling microcirculation in states of decreased tissue oxygen. Because intravascular hemolysis might also contribute to plasma ATP, we tested in vitro which portion of ATP release is due to hemolysis in typical exercise-induced strains to the red blood cells (shear stress, deoxygenation, and lactic acidosis). Human erythrocytes were suspended in dextran-containing media (hematocrit 10%) and were exposed to shear stress in a rotating Couette viscometer at 37°C. Desaturation (oxygen saturation of hemoglobin ∼20%) was achieved by tonometry with N2 before shear stress exposure. Cells not exposed to shear stress were used as controls. Na lactate (15 mM), lactic acid (15 mM, pH 7.0), and HCl (pH 7.0) were added to simulate exercise-induced lactic acidosis. After incubation, extracellular hemoglobin was measured to quantify hemolysis. ATP was measured with the luciferase assay. Shear stress increased extracellular ATP in a stress-related and time-dependent manner. Hypoxia induced a ∼10-fold increase in extracellular ATP in nonsheared cells and shear stress-exposed cells. Lactic acid had no significant effect on ATP release and hemolysis. In normoxic cells, approximately 20%-50% of extracellular ATP was due to hemolysis. This proportion decreased to less than 10% in hypoxic cells. Our results indicate that when exposing red blood cells to typical strains they encounter when passing through capillaries of exercising skeletal muscle, ATP release from red blood cells is caused mainly by deoxygenation and shear stress, whereas lactic acidosis had only a minor effect. Hemolysis effects were decreased when hemoglobin was deoxygenated. Together, by specific release and hemolysis, extracellular ATP reaches values that have been shown to cause local vasodilatation.

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)

Non-invasive spectroscopy of transfusable red blood cells stored inside sealed plastic blood-bags.

PubMed

Buckley, K; Atkins, C G; Chen, D; Schulze, H G; Devine, D V; Blades, M W; Turner, R F B

2016-03-07

After being separated from (donated) whole blood, red blood cells are suspended in specially formulated additive solutions and stored (at 4 °C) in polyvinyl chloride (PVC) blood-bags until they are needed for transfusion. With time, the prepared red cell concentrate (RCC) is known to undergo biochemical changes that lower effectiveness of the transfusion, and thus regulations are in place that limit the storage period to 42 days. At present, RCC is not subjected to analytical testing prior to transfusion. In this study, we use Spatially Offset Raman Spectroscopy (SORS) to probe, non-invasively, the biochemistry of RCC inside sealed blood-bags. The retrieved spectra compare well with conventional Raman spectra (of sampled aliquots) and are dominated by features associated with hemoglobin. In addition to the analytical demonstration that SORS can be used to retrieve RCC spectra from standard clinical blood-bags without breaking the sterility of the system, the data reveal interesting detail about the oxygenation-state of the stored cells themselves, namely that some blood-bags unexpectedly contain measurable amounts of deoxygenated hemoglobin after weeks of storage. The demonstration that chemical information can be obtained non-invasively using spectroscopy will enable new studies of RCC degeneration, and points the way to a Raman-based instrument for quality-control in a blood-bank or hospital setting.

Red blood cell indices and prevalence of hemoglobinopathies and glucose 6 phosphate dehydrogenase deficiencies in male Tanzanian residents of Dar es Salaam.

PubMed

Mwakasungula, Solomon; Schindler, Tobias; Jongo, Said; Moreno, Elena; Kamaka, Kasimu; Mohammed, Mgeni; Joseph, Selina; Rashid, Ramla; Athuman, Thabit; Tumbo, Anneth Mwasi; Hamad, Ali; Lweno, Omar; Tanner, Marcel; Shekalaghe, Seif; Daubenberger, Claudia A

2014-01-01

Hemoglobinopathies, disorders of hemoglobin structure and production, are one of the most common monogenic disorders in humans. Glucose 6 phosphate dehydrogenase deficiency (G6PD) is an inherited enzymopathy resulting in increased oxygen stress susceptibility of red blood cells. The distributions of these genetic traits in populations living in tropical and subtropical regions where malaria has been or is still present are thought to result from survival advantage against severe life threatening malaria disease. 384 male Tanzanian volunteers residing in Dar es Salaam were typed for G6PD, sickle cell disease and α-thalassemia. The most prominent red blood cell polymorphism was heterozygous α(+)-thalassemia (37.8%), followed by the G6PD(A) deficiency (16.4%), heterozygous sickle cell trait (15.9%), G6PD(A-) deficiency (13.5%) and homozygous α(+)-thalassemia (5.2%). 35%, 45%, 17% and 3% of these volunteers were carriers of wild type gene loci, one, two or three of these hemoglobinopathies, respectively. We find that using a cut off value of 28.6 pg. for mean corpuscular hemoglobin (MCH), heterozygous α(+)-thalassemia can be predicted with a sensitivity of 84% and specificity of 72% in this male population. All subjects carrying homozygous α(+)-thalassemia were identified based on their MCH value < 28.6 pg.

A case of red-cell adenosine deaminase overproduction associated with hereditary hemolytic anemia found in Japan.

PubMed

Miwa, S; Fujii, H; Matsumoto, N; Nakatsuji, T; Oda, S; Asano, H; Asano, S

1978-01-01

A case of red cell adenosine deaminase (ADA) overproduction associated with hereditary hemolytic anemia is reported here. This appears to be the second report. Proband is a 38-year-old Japanese male who had hemoglobin, 15.8 g/100 ml; reticulocyte count, 4.5%; serum indirect bilirubin, 4.9 mg/100 ml; 51Cr-labeled red cell half-life, 12 days; red cells showed moderate stomatocytosis. His red cell ADA activity showed 40-fold increase while that of the mother showed 4-fold increase. The mother was hematologically normal. The father had a normal enzyme activity. The proband and the mother showed slightly high serum uric acid levels. The proband's red cell showed: ATP, 628 nmoles/ml (normal, 1,010--1,550); adenine nucleotide pool, 46% of the normal mean; 2,3-diphosphoglycerate content, 3,782 nmoles/ml (normal 4,170--5,300); increased oxygen affinity of hemoglobin, P50 of intact erythrocytes being 21.8 mmHg (normal, 24.1--26.1). Red cell glycolytic intermediates in the proband were low in general, and the rate of lactate production was low. Kinetic studies using crude hemolysate revealed a normal Km for adenosine, normal electrophoretic mobility but slightly abnormal pH curve and slightly low utilization of 2-deoxyadenosine. The ADA activity of lymphocytes was nearly normal.

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

Genetic resistance to malaria, oxidative stress and hemoglobin oxidation.

PubMed

Destro Bisol, G

1999-09-01

I describe a model which posits the molecular basis of some malaria-resistance genes in the interaction between oxidized hemoglobin and membrane components. The model is supported by a considerable body of evidence which indicates that erythrocytes of genetically protected individuals (carriers of sickle cell trait, alpha- and beta-thalassemia, and G6PD deficiency) are susceptible to the increase of oxidation of hemoglobin following H2O2 release in the host cell by Plasmodium falciparum. I suggest that the irreversible interaction between oxidized hemoglobin and the red cell membrane could trigger mechanisms that: (i) reduce invasion of erythrocytes by the falciparum parasite; (ii) impair parasite survival and development within the cell; (iii) accelerate infected erythrocyte clearance by phagocytosis.

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.

Hearing Loss and Auditory Function in Sickle Cell Disease

ERIC Educational Resources Information Center

Burch-Sims, G.P.; Matlock, V.R.

2005-01-01

Sickle cell disease was first reported in 1910 by J. Herrick, and since then, various associated conditions and complications have been described. Sickle cell disease is a hereditary disorder characterized by abnormality of the hemoglobin in the red blood cell. During periods of decreased oxygen tension in the red blood cell's environment, the…

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

PubMed

Castilho, E M; Glass, M L; Manço, J C

2003-06-01

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

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.

Cost-effective and Rapid Blood Analysis on a Cell-phone

PubMed Central

Zhu, Hongying; Sencan, Ikbal; Wong, Justin; Dimitrov, Stoyan; Tseng, Derek; Nagashima, Keita; Ozcan, Aydogan

2013-01-01

We demonstrate a compact and cost-effective imaging cytometry platform installed on a cell-phone for the measurement of the density of red and white blood cells as well as hemoglobin concentration in human blood samples. Fluorescent and bright-field images of blood samples are captured using separate optical attachments to the cell-phone and are rapidly processed through a custom-developed smart application running on the phone for counting of blood cells and determining hemoglobin density. We evaluated the performance of this cell-phone based blood analysis platform using anonymous human blood samples and achieved comparable results to a standard bench-top hematology analyser. Test results can either be stored on the cell-phone memory or be transmitted to a central server, providing remote diagnosis opportunities even in field settings. PMID:23392286

Cost-effective and rapid blood analysis on a cell-phone.

PubMed

Zhu, Hongying; Sencan, Ikbal; Wong, Justin; Dimitrov, Stoyan; Tseng, Derek; Nagashima, Keita; Ozcan, Aydogan

2013-04-07

We demonstrate a compact and cost-effective imaging cytometry platform installed on a cell-phone for the measurement of the density of red and white blood cells as well as hemoglobin concentration in human blood samples. Fluorescent and bright-field images of blood samples are captured using separate optical attachments to the cell-phone and are rapidly processed through a custom-developed smart application running on the phone for counting of blood cells and determining hemoglobin density. We evaluated the performance of this cell-phone based blood analysis platform using anonymous human blood samples and achieved comparable results to a standard bench-top hematology analyser. Test results can either be stored on the cell-phone memory or be transmitted to a central server, providing remote diagnosis opportunities even in field settings.

The Mechanism of Blood Function and Production After Injury.

DTIC Science & Technology

1980-02-01

radioactive 59Fe labeled red cell dilution method described by Garcia7 . Red cell 2,3 diphosphoglycerate levels were measured using a commercial kit...and protein depleted rats was also associated with elevated 2,3 diphosphoglycerate levels (p<.05)(Table IV) suggesting partial compensation for anemic...Brewer, G.J.: The relationship between red cell 2,3 diphosphoglycerate and levels of hemoglobin in the human. Proc.Soc. Exp.Biol.Med. 150(1): 215-9

Optical wavelength selection for portable hemoglobin determination by near-infrared spectroscopy method

NASA Astrophysics Data System (ADS)

Tian, Han; Li, Ming; Wang, Yue; Sheng, Dinggao; Liu, Jun; Zhang, Linna

2017-11-01

Hemoglobin concentration is commonly used in clinical medicine to diagnose anemia, identify bleeding, and manage red blood cell transfusions. The golden standard method for determining hemoglobin concentration in blood requires reagent. Spectral methods were advantageous at fast and non-reagent measurement. However, model calibration with full spectrum is time-consuming. Moreover, it is necessary to use a few variables considering size and cost of instrumentation, especially for a portable biomedical instrument. This study presents different wavelength selection methods for optical wavelengths for total hemoglobin concentration determination in whole blood. The results showed that modelling using only two wavelengths combination (1143 nm, 1298 nm) can keep on the fine predictability with full spectrum. It appears that the proper selection of optical wavelengths can be more effective than using the whole spectra for determination hemoglobin in whole blood. We also discussed the influence of water absorptivity on the wavelength selection. This research provides valuable references for designing portable NIR instruments determining hemoglobin concentration, and may provide some experience for noninvasive hemoglobin measurement by NIR methods.

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.

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

Rouyer-Fessard, P.; Garel, M.C.; Domenget, C.

The soluble pool of alpha hemoglobin chains present in blood or bone marrow cells was measured with a new affinity method using a specific probe, beta A hemoglobin chain labeled with ({sup 3}H)N-ethylmaleimide. This pool of soluble alpha chains was 0.067 {plus minus} 0.017% of hemoglobin in blood of normal adult, 0.11 {plus minus} 0.03% in heterozygous beta thalassemia and ranged from 0.26 to 1.30% in homozygous beta thalassemia intermedia. This elevated pool of soluble alpha chains observed in human beta thalassemia intermedia decreased 33-fold from a value of 10% of total hemoglobin in bone marrow cells to 0.3% inmore » the most dense red blood cells. The amount of insoluble alpha chains was measured by using the polyacrylamide gel electrophoresis in urea and Triton X-100. In beta thalassemia intermedia the amount of insoluble alpha chains was correlated with the decreased spectrin content of red cell membrane and was associated with a decrease in ankyrin and with other abnormalities of the electrophoretic pattern of membrane proteins. The loss and topology of the reactive thiol groups of membrane proteins was determined by using ({sup 3}H)N-ethylmaleimide added to membrane ghosts prior to urea and Triton X-100 electrophoresis. Spectrin and ankyrin were the major proteins with the most important decrease of thiol groups.« less

Clinical factors and the decision to transfuse chronic dialysis patients.

PubMed

Whitman, Cynthia B; Shreay, Sanatan; Gitlin, Matthew; van Oijen, Martijn G H; Spiegel, Brennan M R

2013-11-01

Red blood cell transfusion was previously the principle therapy for anemia in CKD but became less prevalent after the introduction of erythropoiesis-stimulating agents. This study used adaptive choice-based conjoint analysis to identify preferences and predictors of transfusion decision-making in CKD. A computerized adaptive choice-based conjoint survey was administered between June and August of 2012 to nephrologists, internists, and hospitalists listed in the American Medical Association Masterfile. The survey quantified the relative importance of 10 patient attributes, including hemoglobin levels, age, occult blood in stool, severity of illness, eligibility for transplant, iron indices, erythropoiesis-stimulating agents, cardiovascular disease, and functional status. Triggers of transfusions in common dialysis scenarios were studied, and based on adaptive choice-based conjoint-derived preferences, relative importance by performing multivariable regression to identify predictors of transfusion preferences was assessed. A total of 350 providers completed the survey (n=305 nephrologists; mean age=46 years; 21% women). Of 10 attributes assessed, absolute hemoglobin level was the most important driver of transfusions, accounting for 29% of decision-making, followed by functional status (16%) and cardiovascular comorbidities (12%); 92% of providers transfused when hemoglobin was 7.5 g/dl, independent of other factors. In multivariable regression, Veterans Administration providers were more likely to transfuse at 8.0 g/dl (odds ratio, 5.9; 95% confidence interval, 1.9 to 18.4). Although transplant eligibility explained only 5% of decision-making, nephrologists were five times more likely to value it as important compared with non-nephrologists (odds ratio, 5.2; 95% confidence interval, 2.4 to 11.1). Adaptive choice-based conjoint analysis was useful in predicting influences on transfusion decisions. Hemoglobin level, functional status, and cardiovascular comorbidities most strongly influenced transfusion decision-making, but preference variations were observed among subgroups.

Trpc2 Depletion Protects RBC from Oxidative Stress-Induced Hemolysis

PubMed Central

Hirschler-Laszkiewicz, Iwona; Zhang, Wenyi; Keefer, Kerry; Conrad, Kathleen; Tong, Qin; Chen, Shu-jen; Bronson, Sarah; Cheung, Joseph Y.; Miller, Barbara A.

2011-01-01

Transient receptor potential channels Trpc2 and Trpc3 are expressed on normal murine erythroid precursors, and erythropoietin stimulates an increase in intracellular calcium ([Ca2+]i) through TRPC2 and TRPC3. Because modulation of [Ca2+]i is an important signaling pathway in erythroid proliferation and differentiation, Trpc2, Trpc3, and Trpc2/Trpc3 double knockout mice were utilized to explore the roles of these channels in erythropoiesis. Trpc2, Trpc3, and Trpc2/Trpc3 double knockout mice were not anemic, and had similar red blood cell counts, hemoglobins, and reticulocyte counts as wild type littermate controls. Although the erythropoietin induced increase in [Ca2+]i was reduced, these knockout mice showed no defects in red cell production. The major phenotypic difference at steady state was that the mean corpuscular volume, mean corpuscular hemoglobin, and hematocrit of red cells were significantly greater in Trpc2 and Trpc2/Trpc3 double knockout mice, and mean corpuscular hemoglobin concentration was significantly reduced. All hematological parameters in Trpc3 knockout mice were similar to controls. When exposed to phenyhydrazine, unlike the Trpc3 knockouts, Trpc2 and Trpc2/Trpc3 double knockout mice showed significant resistance to hemolysis. This was associated with significant reduction in hydrogen peroxide-induced calcium influx in erythroblasts. While erythropoietin induced calcium influx through TRPC2 or TRPC3 is not critical for erythroid production, these data demonstrate that TRPC2 plays an important role in oxidative stress-induced hemolysis which may be related to reduced calcium entry in red cells in the presence of Trpc2 depletion. PMID:21924222

Improving outcome of trauma patients by implementing patient blood management.

PubMed

Füllenbach, Christoph; Zacharowski, Kai; Meybohm, Patrick

2017-04-01

Patient blood management aims to improve patient outcome and safety by reducing the number of unnecessary red blood cell transfusions and vitalizing patient-specific anemia reserves. While this is increasingly recognized as best clinical practice in elective surgery, the implementation in the setting of trauma is restrained because of typically nonelective (emergency) surgery and, in specific circumstances, allogeneic blood transfusions as life-saving therapy. Viscoelastic diagnostics allow a precise identification of trauma-induced coagulopathy. A coagulation factor concentrate-based therapy is increasingly recognized as a fast and effective concept to correct coagulopathy and minimize blood loss. Using smaller tubes has a great potential to reduce the severity of phlebotomy-induced anemia. Washed cell salvage may reduce the number of allogeneic blood transfusions. Intravenous iron (with or without erythropoietin) may result in an increase of hemoglobin levels and reduced red blood cell transfusion requirements. Although a restrictive transfusion strategy is recommended in general, a target hemoglobin level of 7-9 g/dl is recommended in acute bleeding patients. In the setting of trauma, options to avoid unnecessary blood loss and reduce blood transfusion are manifold. These are likely to improve safety and outcome of trauma patients while potentially reducing therapeutic costs.

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.

Hemoglobin Threshold for Blood Transfusion in a Pediatric Intensive Care Unit.

PubMed

Chegondi, Madhuradhar; Sasaki, Jun; Raszynski, André; Totapally, Balagangadhar R

2016-07-01

To evaluate the hemoglobin threshold for red cell transfusion in children admitted to a pediatric intensive care unit (PICU). Retrospective chart review study. Tertiary care PICU. Critically ill pediatric patients requiring blood transfusion. No intervention. We analyzed the charts of all children between 1 month and 21 years of age who received packed red blood cell (PRBC) transfusions during a 2-year period. The target patients were identified from our blood bank database. For analysis, the patients were subdivided into four groups: acute blood loss (postsurgically, trauma, or acute gastrointestinal bleeding from other causes), hematologic (hematologic malignancies, bone marrow suppression, hemolytic anemia, or sickle cell disease), unstable (FiO 2 > 0.6 and/or on inotropic support), and stable groups. We also compared the pre-transfusion hemoglobin threshold in all unstable patients with that of all stable patients. A total of 571 transfusion episodes in 284 patients were analyzed. 28% (n = 160) of transfusions were administered to patients in the acute blood loss group, 36% (n = 206) to hematologic patients, 17% (n = 99) to unstable patients, and 18% (n = 106) to stable patients. The mean pre-transfusion hemoglobin (± SD) in all children as well as in the acute blood loss, hematologic, unstable and stable groups was 7.3 ± 1.20, 7.83 ± 1.32, 6.97 ± 1.31, 7.96 ± 1.37, 7.31 ± 1.09 g/dl, respectively. The transfusion threshold for acute blood loss and unstable groups was higher compared to hematologic and stable groups (p < 0.001; ANOVA with multiple comparisons). The mean pre-transfusion hemoglobin threshold for stable and unstable patients among all groups was 7.3 ± 1.3 and 7.9 ± 1.3 (p < 0.0001), respectively. The observed mortality rate was higher among children who received transfusion compared to other children admitted to PICU. The hemoglobin threshold for transfusion varied according to clinical conditions. Overall, the hemoglobin threshold for transfusion was 7.3 ± 1.20 g/dl.

Biofortified red mottled beans (phaseolus vulgaris L.) in a maize and bean diet provide more bioavailable iron than standard red mottled beans: studies in poultry (Gallus gallus) and an in vitro digestion/Caco-2 model

USDA-ARS?s Scientific Manuscript database

The objective was to compare the capacities of biofortified and standard colored beans to deliver iron (Fe) for hemoglobin synthesis. Two isolines of large-seeded, red mottled Andean beans (Phaseolus valgaris L.), one standard (“Low FE”) and the other biofortified (“High Fe”) in Fe (49 and 71 ug Fe...

Liquid Storage at 4 deg C of Previously Frozen Red Cells

DTIC Science & Technology

1987-12-01

adenosine tnphosphate (ATP). 2.3- acceptable red cell function. A post-thaw storage ca- diphosphoglycerate (2.3-DPG), glucose, supernatant hemo...and Received for publication September 22. 1986; revision received supernatant hemoglobin levels within the acceptable range, November 29, 1986, and...percent. All units were sterile at the end of the 21-day post- thaw storage period. 6.9 The mean red cell ATP and 2,3-DPG levels are shown in Figure 1

Visualization of hemodynamics and light scattering in exposed brain of rat using multispectral image reconstruction based on Wiener estimation method

NASA Astrophysics Data System (ADS)

Nishidate, Izumi; Ishizuka, Tomohiro; Yoshida, Keiichiro; Kawauchi, Satoko; Sato, Shunichi; Sato, Manabu

2015-07-01

We investigate a method to estimate the spectral images of reduced scattering coefficients and the absorption coefficients of in vivo exposed brain tissues in the range from visible to near-infrared wavelength (500-760 nm) based on diffuse reflectance spectroscopy using a digital RGB camera. In the proposed method, the multi-spectral reflectance images of in vivo exposed brain are reconstructed from the digital red, green, blue images using the Wiener estimation algorithm. The Monte Carlo simulation-based multiple regression analysis for the absorbance spectra is then used to specify the absorption and scattering parameters of brain tissue. In this analysis, the concentration of oxygenated hemoglobin and that of deoxygenated hemoglobin are estimated as the absorption parameters whereas the scattering amplitude a and the scattering power b in the expression of μs'=aλ-b as the scattering parameters, respectively. The spectra of absorption and reduced scattering coefficients are reconstructed from the absorption and scattering parameters, and finally, the spectral images of absorption and reduced scattering coefficients are estimated. We performed simultaneous recordings of spectral diffuse reflectance images and of the electrophysiological signals for in vivo exposed rat brain during the cortical spreading depression evoked by the topical application of KCl. Changes in the total hemoglobin concentration and the tissue oxygen saturation imply the temporary change in cerebral blood flow during CSD. Change in the reduced scattering coefficient was observed before the profound increase in the total hemoglobin concentration, and its occurrence was synchronized with the negative dc shift of the local field potential.

Effectiveness of Provider Education Followed by Computerized Provider Order Entry Alerts in Reducing Inappropriate Red Blood Cell Transfusion.

PubMed

Patel, Vijay M; Rains, Anna W; Clark, Christopher T

2016-01-01

To reduce the rate of inappropriate red blood cell transfusion, a provider education program, followed by alerts in the computerized provider order entry system (CPOE), was established to encourage AABB transfusion guidelines. Metrics were established for nonemergent inpatient transfusions. Service lines with high order volume were targeted with formal education regarding AABB 2012 transfusion guidelines. Transfusion orders were reviewed in real time with email communications sent to ordering providers falling outside of AABB recommendations. After 12 months of provider education, alerts were activated in CPOE. With provider education alone, the incidence of pretransfusion hemoglobin levels greater than 8 g/dL decreased from 16.64% to 6.36%, posttransfusion hemoglobin levels greater than 10 g/dL from 14.03% to 3.78%, and number of nonemergent two-unit red blood cell orders from 45.26% to 22.66%. Red blood cell utilization decreased by 13%. No additional significant reduction in nonemergent two-unit orders was observed with CPOE alerts. Provider education, an effective and low-cost method, should be considered as a first-line method for reducing inappropriate red blood cell transfusion rates in stable adult inpatients. Alerts in the computerized order entry system did not significantly lower the percentage of two-unit red blood cells orders but may help to maintain educational efforts.

Digital image analysis of fingernail colour in cadavers comparing carbon monoxide poisoning to controls.

PubMed

Langlois, Neil E I

2010-03-01

Carbon monoxide is a component of motor vehicle exhaust fumes, provided a functional catalytic converter is not present. This gas binds avidly to the hemoglobin molecule in red blood cells preventing its oxygen transport function, effectively poisoning the body by starving it of oxygen. In binding to hemoglobin, carbon monoxide forms carboxyhemoglobin, which has a characteristic bright pink color. It has been remarked that the fingernails of victims of carbon monoxide tend to exhibit pink color, otherwise fingernails of deceased bodies tend towards a dark red to blue color. This study sought to objectively determine by using digital image analysis if a color difference occurred between the fingernails of a group of cadavers with carbon monoxide poisoning compared to a group of controls. The fingernails of the carbon monoxide group did tend to be more red than the controls, but due to overlap between the two groups assessment of the fingernails cannot be recommended as a rapid screening test.

Multi-spectral imaging of oxygen saturation

NASA Astrophysics Data System (ADS)

Savelieva, Tatiana A.; Stratonnikov, Aleksander A.; Loschenov, Victor B.

2008-06-01

The system of multi-spectral imaging of oxygen saturation is an instrument that can record both spectral and spatial information about a sample. In this project, the spectral imaging technique is used for monitoring of oxygen saturation of hemoglobin in human tissues. This system can be used for monitoring spatial distribution of oxygen saturation in photodynamic therapy, surgery or sports medicine. Diffuse reflectance spectroscopy in the visible range is an effective and extensively used technique for the non-invasive study and characterization of various biological tissues. In this article, a short review of modeling techniques being currently in use for diffuse reflection from semi-infinite turbid media is presented. A simple and practical model for use with a real-time imaging system is proposed. This model is based on linear approximation of the dependence of the diffuse reflectance coefficient on relation between absorbance and reduced scattering coefficient. This dependence was obtained with the Monte Carlo simulation of photon propagation in turbid media. Spectra of the oxygenated and deoxygenated forms of hemoglobin differ mostly in the red area (520 - 600 nm) and have several characteristic points there. Thus four band-pass filters were used for multi-spectral imaging. After having measured the reflectance, the data obtained are used for fitting the concentration of oxygenated and free hemoglobin, and hemoglobin oxygen saturation.

Red blood cell transfusion in newborn infants

PubMed Central

Whyte, Robin K; Jefferies, Ann L

2014-01-01

Red blood cell transfusion is an important and frequent component of neonatal intensive care. The present position statement addresses the methods and indications for red blood cell transfusion of the newborn, based on a review of the current literature. The most frequent indications for blood transfusion in the newborn are the acute treatment of perinatal hemorrhagic shock and the recurrent correction of anemia of prematurity. Perinatal hemorrhagic shock requires immediate treatment with large quantities of red blood cells; the effects of massive transfusion on other blood components must be considered. Some guidelines are now available from clinical trials investigating transfusion in anemia of prematurity; however, considerable uncertainty remains. There is weak evidence that cognitive impairment may be more severe at follow-up in extremely low birth weight infants transfused at lower hemoglobin thresholds; therefore, these thresholds should be maintained by transfusion therapy. Although the risks of transfusion have declined considerably in recent years, they can be minimized further by carefully restricting neonatal blood sampling. PMID:24855419

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

Altered peripheral profile of blood cells in Alzheimer disease

PubMed Central

Chen, Si-Han; Bu, Xian-Le; Jin, Wang-Sheng; Shen, Lin-Lin; Wang, Jun; Zhuang, Zheng-Qian; Zhang, Tao; Zeng, Fan; Yao, Xiu-Qing; Zhou, Hua-Dong; Wang, Yan-Jiang

2017-01-01

Abstract Alzheimer disease (AD) has been made a global priority for its multifactorial pathogenesis and lack of disease-modifying therapies. We sought to investigate the changes of profile of blood routine in AD and its correlation with the disease severity. In all, 92 AD patients and 84 age and sex-matched normal controls were enrolled and their profiles of blood routine were evaluated. Alzheimer disease patients had increased levels of mean corpuscular hemoglobin, mean corpuscular volume, red cell distribution width-standard deviation, mean platelet volume,and decreased levels of platelet distribution width, red blood cell, hematocrit, hemoglobin, lymphocyte, and basophil compared with normal controls. Alterations in quantity and quality of blood cells may be involved in the pathogenesis of AD and contribute to the disease progression. PMID:28538375

Preoperative Anemia in Cardiac Operation: Does Hemoglobin Tell the Whole Story?

PubMed

Dai, Lu; Mick, Stephanie L; McCrae, Keith R; Houghtaling, Penny L; Sabik, Joseph F; Blackstone, Eugene H; Koch, Colleen G

2018-01-01

Preoperative anemia, defined by hemoglobin level, is associated with elevated risk after cardiac operation. Better understanding of anemia requires characterization beyond this. This investigation focuses on red cell size and its association with patient characteristics and outcomes after cardiac operation. From January 2010 to January 2014, 10,589 patients underwent elective cardiac operations at Cleveland Clinic. Anemia was characterized as normocytic, microcytic, or macrocytic based on mean corpuscular volume (MCV). Models for hospital complications were developed using multivariable logistic regression. Other outcomes were postoperative transfusion and intensive care unit (ICU) and postoperative hospital lengths of stay. A total of 2,715 patients (26%) were anemic. Of these, 2,365 (87%) had normocytic, 219 (8.1%) microcytic, and 131 (4.8%) macrocytic anemia. Non-anemic patients (n = 2,041, 26%) received transfusions compared with 1,553 (66%) normocytic, 148 (68%) microcytic, and 97 (74%) macrocytic anemia patients. Patients with normocytic or macrocytic anemia had more renal failure (normocytic: odds ratio (OR) 1.9, macrocytic: OR 3.5), other complications (normocytic: OR 1.3, macrocytic: OR 2.2) and death (normocytic: OR 2.0, macrocytic: OR 6.2) than non-anemic patients; patients with microcytic anemia had fewer reoperations (OR 0.35) and less postoperative atrial fibrillation (OR 0.50). Anemic patients experienced longer ICU (27 versus 48 hours, p < 0.001) and postoperative hospital (6.1 versus 7.4 days, p < 0.001) length of stay than non-anemic patients. Cardiac surgical patients are often anemic. Demographic characteristics, comorbidities, and outcomes are dissimilar according to red cell size. Patients with microcytic anemia had the lowest hemoglobin levels, yet the best clinical outcomes among anemic patients. MCV from the standard complete blood count adds additional information beyond hemoglobin for targeted intervention. Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Seasonal variations in red deer (Cervus elaphus) hematology related to antler growth and biometrics measurements.

PubMed

Gaspar-López, Enrique; Landete-Castillejos, Tomás; Estevez, Jose Antonio; Ceacero, Francisco; Gallego, Laureano; García, Andrés Jose

2011-04-01

The aim of the study was to relate seasonal hematology changes with the rest of physiological variations suffered by red deer, such as antler and biometrics cycle, and to assess the relationship between hematology and the effort performed in antler development. Blood samples were taken from 21 male red deer every 4 weeks during 18 months. Samples were analyzed for the main hematological parameters. Simultaneously, biometrics measurements were taken, such as antler length, body weight, body condition score, testicular diameter (TD), and thoracic and neck girth. All the blood cell types (erythrocytes, leukocytes, and platelets) showed seasonal variations, increasing as antler cleaning approached, as did hematocrit and hemoglobin. The final size of antlers was negatively related to leukocyte count, nonlymphoid leukocyte count, red cell distribution width, mean corpuscular hemoglobin, mean platelet volume, and TD, whereas it was positively related to body condition during antler growth. Huge seasonal variations in some hematological values have been found to be related to changes in antler and biometrics measurements. Since these variations are even greater than the caused by deer handling, they should be taken into account when evaluating hematology in deer populations. Copyright © 2011 Wiley-Liss, Inc., A Wiley Company.

Red blood cells release factors with growth and survival bioactivities for normal and leukemic T cells.

PubMed

Antunes, Ricardo F; Brandão, Cláudia; Maia, Margarida; Arosa, Fernando A

2011-01-01

Human red blood cells are emerging as a cell type capable to regulate biological processes of neighboring cells. Hereby, we show that human red blood cell conditioned media contains bioactive factors that favor proliferation of normal activated T cells and leukemic Jurkat T cells, and therefore called erythrocyte-derived growth and survival factors. Flow cytometry and electron microscopy in parallel with bioactivity assays revealed that the erythrocyte factors are present in the vesicle-free supernatant, which contains up to 20 different proteins. The erythrocyte factors are thermosensitive and do not contain lipids. Native polyacrylamide gel electrophoresis followed by passive elution and mass spectrometry identification reduced the potential erythrocyte factors to hemoglobin and peroxiredoxin II. Two-dimensional differential gel electrophoresis of the erythrocyte factors revealed the presence of multiple hemoglobin oxy-deoxy states and peroxiredoxin II isoforms differing in their isoelectric point akin to the presence of β-globin chains. Our results show that red blood cells release protein factors with the capacity to sustain T-cell growth and survival. These factors may have an unforeseen role in sustaining malignant cell growth and survival in vivo.

Polycythemia vera.

PubMed

Stuart, Brian J; Viera, Anthony J

2004-05-01

Polycythemia vera is a chronic myeloproliferative disorder characterized by increased red blood cell mass. The resultant hyperviscosity of the blood predisposes such patients to thrombosis. Polycythemia vera should be suspected in patients with elevated hemoglobin or hematocrit levels, splenomegaly, or portal venous thrombosis. Secondary causes of increased red blood cell mass (e.g., heavy smoking, chronic pulmonary disease, renal disease) are more common than polycythemia vera and must be excluded. Diagnosis is made using criteria developed by the Polycythemia Vera Study Group; major criteria include elevated red blood cell mass, normal oxygen saturation, and palpable splenomegaly. Untreated patients may survive for six to 18 months, whereas adequate treatment may extend life expectancy to more than 10 years. Treatment includes phlebotomy with the possible addition of myelosuppressive agents based on a risk-stratified approach. Agents under investigation include interferon alfa-2b, anagrelide, and aspirin. Consultation with a hematologist is recommended.

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

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

Swelling hemoglobin CC erythrocytes stimulates a ouabain-insensitive K flux that restores original cell volume. Studies were performed with the K analog, /sup 86/Rb. This volume regulatory pathway was characterized for its anion dependence, sensitivity to loop diuretics, and requirement for Na. The swelling-induced K flux was eliminated if intracellular chloride was replaced by nitrate and both swelling-activated K influx and efflux were partially inhibited by 1 mM furosemide or bumetanide. K influx in swollen hemoglobin CC cells was not diminished when Na in the incubation medium was replaced with choline, indicating Na independence of the swelling-induced flux. Identical experiments withmore » hemoglobin AA cells also demonstrated a swelling-induced increase in K flux, but the magnitude and duration of this increase were considerably less than that seen with hemoglobin CC cells. The increased K flux in hemoglobin AA cells was likewise sensitive to anion replacement and to loop diuretics and did not require the presence of Na. These data indicate that a volume-activated K pathway with similar transport characteristics exists in both hemoglobin CC and AA red cells.« less

The role of hemoglobin oxygen affinity in oxygen transport at high altitude.

PubMed

Winslow, Robert M

2007-09-30

Hemoglobin is involved in the regulation of O(2) transport in two ways: a long-term adjustment in red cell mass is mediated by erythropoietin (EPO), a response to renal oxgyenation. Short-term, rapid-response adjustments are mediated by ventilation, cardiac output, hemoglobin oxygen affinity (P50), barriers to O(2) diffusion, and the control of local microvascular tissue perfusion. The distribution of O(2) between dissolved (PO2) and hemoglobin-bound (saturation) is the familiar oxygen equilibrium curve, whose position is noted as P50. Human hemoglobin is not genetically adapted for function at high altitude. However, more specialized species native to high altitudes (guinea pig and bar-headed goose, for example) seem to have a lower P50 than their sea level counterparts, an adaptation that presumably promotes O(2) uptake from a hypoxic environment. Humans, native to very high altitude either in the Andes or Himalayan mountains, also can increase O(2) affinity, not because of a fundamental difference in hemoglobin structure or function, but because of extreme hyperventilation and alkalosis.

Red blood cell aggregation, aggregate strength and oxygen transport potential of blood are abnormal in both homozygous sickle cell anemia and sickle-hemoglobin C disease.

PubMed

Tripette, Julien; Alexy, Tamas; Hardy-Dessources, Marie-Dominique; Mougenel, Daniele; Beltan, Eric; Chalabi, Tawfik; Chout, Roger; Etienne-Julan, Maryse; Hue, Olivier; Meiselman, Herbert J; Connes, Philippe

2009-08-01

Recent evidence suggests that red blood cell aggregation and the ratio of hematocrit to blood viscosity (HVR), an index of the oxygen transport potential of blood, might considerably modulate blood flow dynamics in the microcirculation. It thus seems likely that these factors could play a role in sickle cell disease. We compared red blood cell aggregation characteristics, blood viscosity and HVR at different shear rates between sickle cell anemia and sickle cell hemoglobin C disease (SCC) patients, sickle cell trait carriers (AS) and control individuals (AA). Blood viscosity determined at high shear rate was lower in sickle cell anemia (n=21) than in AA (n=52), AS (n=33) or SCC (n=21), and was markedly increased in both SCC and AS. Despite differences in blood viscosity, both sickle cell anemia and SCC had similar low HVR values compared to both AA and AS. Sickle cell anemia (n=21) and SCC (n=19) subjects had a lower red blood cell aggregation index and longer time for red blood cell aggregates formation than AA (n=16) and AS (n=15), and a 2 to 3 fold greater shear rate required to disperse red blood cell aggregates. The low HVR levels found in sickle cell anemia and SCC indicates a comparable low oxygen transport potential of blood in both genotypes. Red blood cell aggregation properties are likely to be involved in the pathophysiology of sickle cell disease: the increased shear forces needed to disperse red blood cell aggregates may disturb blood flow, especially at the microcirculatory level, since red blood cell are only able to pass through narrow capillaries as single cells rather than as aggregates.

Interaction between phloretin and the red blood cell membrane

PubMed Central

1976-01-01

Phloretin binding to red blood cell components has been characterized at pH6, where binding and inhibitory potency are maximal. Binding to intact red cells and to purified hemoglobin are nonsaturated processes approximately equal in magnitude, which strongly suggests that most of the red cell binding may be ascribed to hemoglobin. This conclusion is supported by the fact that homoglobin-free red cell ghosts can bind only 10% as much phloretin as an equivalent number of red cells. The permeability of the red cell membrane to phloretin has been determined by a direct measurement at the time-course of the phloretin uptake. At a 2% hematocrit, the half time for phloretin uptake is 8.7s, corresponding to a permeability coefficient of 2 x 10(-4) cm/s. The concentration dependence of the binding to ghosts reveals two saturable components. Phloretin binds with high affinity (K diss = 1.5 muM) to about 2.5 x 10(6) sites per cell; it also binds with lower affinity (Kdiss = 54 muM) to a second (5.5 x 10(7) per cell) set of sites. In sonicated total lipid extracts of red cell ghosts, phloretin binding consists of a single, saturable component. Its affinity and total number of sites are not significantly different from those of the low affinity binding process in ghosts. No high affinity binding of phloretin is exhibited by the red cell lipid extracts. Therefore, the high affinity phloretin binding sites are related to membrane proteins, and the low affinity sites result from phloretin binding to lipid. The identification of these two types of binding sites allows phloretin effects on protein-mediated transport processes to be distinguished from effects on the lipid region of the membrane. PMID:5575

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.

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

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

PubMed

Parrow, Nermi L; Tu, Hongbin; Nichols, James; Violet, Pierre-Christian; Pittman, Corinne A; Fitzhugh, Courtney; Fleming, Robert E; Mohandas, Narla; Tisdale, John F; Levine, Mark

2017-06-01

Decreased erythrocyte deformability, as measured by ektacytometry, may be associated with disease severity in sickle cell anemia (SCA). Heterogeneous populations of rigid and deformable cells in SCA blood result in distortions of diffraction pattern measurements that correlate with the concentration of hemoglobin S (HbS) and the percentage of irreversibly sickled cells. We hypothesize that red cell heterogeneity, as well as deformability, will also be influenced by the concentration of alternative hemoglobins such as fetal hemoglobin (HbF) and the adult variant, HbA 2 . To test this hypothesis, we investigate the relationship between diffraction pattern distortion, osmotic gradient ektacytometry parameters, and the hemoglobin composition of SCA blood. We observe a correlation between the extent of diffraction pattern distortions and percentage of HbF and HbA 2 . Osmotic gradient ektacytometry data indicate that minimum elongation in the hypotonic region is positively correlated with HbF, as is the osmolality at which it occurs. The osmolality at both minimum and maximum elongation is inversely correlated with HbS and HbA 2 . These data suggest that HbF may effectively improve surface-to-volume ratio and osmotic fragility in SCA erythrocytes. HbA 2 may be relatively ineffective in improving these characteristics or cellular hydration at the levels found in this patient cohort. Copyright © 2017. Published by Elsevier Inc.

Imaging the effect of hemoglobin on properties of RBCs using common-path digital holographic microscope

NASA Astrophysics Data System (ADS)

Joglekar, M.; Shah, H.; Trivedi, V.; Mahajan, S.; Chhaniwal, V.; Leitgeb, R.; Javidi, B.; Anand, A.

2017-07-01

Adequate supply of oxygen to the body is the most essential requirement. In vertebrate species this function is performed by Hemoglobin contained in red blood cells. The mass concentration of the Hb determines the oxygen carrying capacity of the blood. Thus it becomes necessary to determine its concentration in the blood, which helps in monitoring the health of a person. If the amount of Hb crosses certain range, then it is considered critical. As the Hb constitutes upto 96% of red blood cells dry content, it would be interesting to examine various physical and mechanical parameters of RBCs which depends upon its concentration. Various diseases bring about significant variation in the amount of hemoglobin which may alter certain parameters of the RBC such as surface area, volume, membrane fluctuation etc. The study of the variations of these parameters may be helpful in determining Hb content which will reflect the state of health of a human body leading to disease diagnosis. Any increase or decrease in the amount of Hb will change the density and hence the optical thickness of the RBCs, which affects the cell membrane and thereby changing its mechanical and physical properties. Here we describe the use of lateral shearing digital holographic microscope for quantifying the cell parameters for studying the change in biophysical properties of cells due to variation in hemoglobin concentration.

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

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.

Efficacy and safety of new complementary feeding guidelines with an emphasis on red meat consumption: a randomized trial in Bogota, Colombia.

PubMed

Olaya, Gilma A; Lawson, Margaret; Fewtrell, Mary S

2013-10-01

Iron deficiency and poor linear growth are common in infants from deprived socioeconomic backgrounds and may be associated with inadequate complementary feeding (CF) practices. We tested the hypothesis that new CF guidelines emphasizing meat as a source of iron and zinc would improve linear growth, iron, and zinc status in infants living in poor socioeconomic circumstances in Bogota, Colombia. A total of 85 term infants who were exclusively breastfed for ≥4 mo were randomly assigned at 6 mo of age to a control group [CG (n = 43); current advice] or intervention group (new guidelines group [NGG (n = 42); with counseling to 1) continue breastfeeding, 2) offer red meat ≥3 d/wk, and 3) offer fruit and vegetables daily]). Main outcomes were 1) linear growth from 6 to 12 mo of age; 2) hemoglobin, hematocrit, iron [serum ferritin (SF)], and zinc status at 12 mo of age; and 3) meat intake at 12 mo of age (by using a food-frequency questionnaire). A total of 38 infants/group provided data at 12 mo of age. NGG infants had significantly higher red meat intake [mean ± SD: 5.4 ± 1.8 compared with 3.5 ± 1.7 d/wk at 12 mo of age; P < 0.001), higher hemoglobin and hematocrit at 12 mo of age, and a significantly greater increase in hemoglobin (mean ± SD change: 0.41 ± 0.8 compared with -0.13 ± 1.0; P = 0.01) and hematocrit (1.04 ± 2.2 compared with -0.15 ± 2.4; P = 0.03) from 6 to 12 mo of age than those in CG infants. There were no significant differences in linear growth from 6 to 12 mo of age or in SF or zinc. The new guidelines showed efficacy with higher red meat intake and positive effects on hemoglobin and hematocrit. The intervention was acceptable and affordable for most mothers. These preliminary results suggest that the intervention merits investigation in a larger cohort with longer-term follow-up. This trial was registered at http://isrctn.org as ISRCTN57733004.

Current controversies in the management of the anemia of prematurity.

PubMed

Bishara, Nader; Ohls, Robin K

2009-02-01

Preterm infants, especially those with extremely low birth weight (ELBW) are exposed to frequent blood draws as part of their care in the neonatal intensive care unit. ELBW infants develop the anemia of prematurity (AOP), a hypo-proliferative anemia marked by inadequate production of erythropoietin (Epo). Treatment of AOP includes red blood cell transfusions, which are given to preterm infants based on indications and guidelines (hematocrit/hemoglobin levels, ventilation and oxygen need, apneas and bradycardias, poor weight gain) that are relatively non-specific. In this article we review recent studies evaluating transfusion guidelines, discuss ways to decrease phlebotomy losses and examine the use of red cell growth factors such as Epo in preventing and treating anemia in preterm infants.

Blood values of the canvasback duck by age, sex and season

USGS Publications Warehouse

Kocan, R.M.; Pitts, S.M.

1976-01-01

Blood samples were obtained from canvasback ducklings from Manitoba and Saskatchewan and from immature and adult canvasbacks on the Mississippi River near LaCrosse, Wisconsin and the Chesapeake Bay. These samples were used to determine baseline data on red cell counts, hematocrit, total protein, glucose, cholesterol, hemoglobin and distribution of plasma proteins. Calculations were also made to determine mean corpuscular volume, mean corpuscular hemoglobin and mean corpuscular hemoglobin concentration. The major differences noted were between ducklings and adults. The former having higher total protein and lower hematocrit, glucose and cholesterol values. These hematologic values were collected in order to provide baseline information on apparently healthy canvasbacks, thereby providing disease investigators with a standard of comparison

21 CFR 862.1590 - Porphobilinogen test system.

Code of Federal Regulations, 2011 CFR

2011-04-01

... intended to measure porphobilinogen (one of the derivatives of hemoglobin which can make the urine a red color) in urine. Measurements obtained by this device are used in the diagnosis and treatment of...

21 CFR 862.1590 - Porphobilinogen test system.

Code of Federal Regulations, 2012 CFR

2012-04-01

... intended to measure porphobilinogen (one of the derivatives of hemoglobin which can make the urine a red color) in urine. Measurements obtained by this device are used in the diagnosis and treatment of...

21 CFR 862.1590 - Porphobilinogen test system.

Code of Federal Regulations, 2013 CFR

2013-04-01

... intended to measure porphobilinogen (one of the derivatives of hemoglobin which can make the urine a red color) in urine. Measurements obtained by this device are used in the diagnosis and treatment of...

Interaction of Jet Fuel Hydrocarbon Components with Red Blood Cells and Hemoglobin

DTIC Science & Technology

2014-06-24

Directorate (RHDJ), Wright-Patterson AFB, OH. The authors would like to thank Maj. Paul Eden, Nicole Schaeublin, Christin Grabinski, Dr. Jeff Gearhart...We would also like to thank LtCol. Norman Fox (Laboratory Flight Commander), Mrs. Nersa Loh (Supervisor, Transfusion Services), and Mr. Dan Fischer ...Approximately 7.8 mg of hemoglobin sample was concentrated into a total volume of 5 mL of Fischer PBS pH 7.5 buffer using an Amicon Centrifugal Filter Unit

Oxygen transport in congenital heart disease: influence of fetal hemoglobin, red cell pH, and 2,3-diphosphoglycerate.

PubMed

Versmold, H T; Linderkamp, C; Döhlemann, C; Riegel, K P

1976-06-01

In 48 individuals (age 1 day to 13 years) with congenital heart disease, blood oxygen transport function was studied in order to evaluate adaptive changes in shunt hypoxemia and to investigate the in vivo regulation of erythrocyte 2, 3-diphosphoglycerate concentration (RBC 2, 3-DPG) in the presence of fetal hemoglobin (HbF). Arterial pO2 and oxygen content, oxygen capacity, acid base status, oxygen affinity, HbF fraction, plasma pH, red cell pH, and RBC 2, 3-DPG were determined. During the first 50 days of life values of standard P50 (stdP50) (37, pH 7.4), actual in vivo P50 (actP50), RBC 2, 3-DPG, O2 capacity, arterial plasma pH, and red cell pH were scattered around the normal range, although tending to low values for stdP50 and arterial plasma pH and to high values for O2 capacity. After the third month, stdP50 actP50, RBC 2, 3-DPG, O2 capacity, and red cell pH were found to be elevated. Plasma pH and actP50 were scattered around the normal range (Figs. 1 and 2). Intraerythrocytic pH in hypoxemic infants was increased compared with normal children when related to plasma pH (Fig. 3). A close to normal intraerythrocytic pH was therefore found in the hypoxemic infants with low plasma pH, and an increased intraerythrocytic pH in the hypoxemic children with normal plasma pH (Fig. 1). A significant negative correlation exists between erythrocyte H+ ion and 2, 3-DPG concentration (Fig. 5); regression constants derived from data at high (mean 47%) and low (mean 9%) fractions of HbF are not significantly different (Regression Equations 8 and 11 in Table 1). Thus, the known difference in 2, 3-DPG binding to fetal or adult deoxyhemoglobin does not measurably influence the erythrocyte 2, 3-DPG concentration, indicating that in vivo the 2, 3-DPG synthesis in hypoxia is virtually regulated by the erythrocyte pH, which in turn is determined by plasma pH and the oxygenation state of hemoglobin.

Construction of an improved amperometric acrylamide biosensor based on hemoglobin immobilized onto carboxylated multi-walled carbon nanotubes/iron oxide nanoparticles/chitosan composite film.

PubMed

Batra, Bhawna; Lata, Suman; Pundir, C S

2013-11-01

A method is described for construction of an improved amperometric acrylamide biosensor based on covalent immobilization of hemoglobin (Hb) onto nanocomposite of carboxylated multi-walled carbon nanotubes (cMWCNT) and iron oxide nanoparticles (Fe3O4NPs) electrodeposited onto Au electrode through chitosan (CHIT) film. The Hb/cMWCNT-Fe3O4NP/CHIT/Au electrode was characterized by scanning electron microscopy, Fourier transform infra-red spectroscopy, electrochemical impedance spectroscopy, and differential pulse voltammetry at different stages of its construction. The biosensor was based on interaction between acrylamide and Hb, which led to decrease in the electroactivity of Hb, i.e., current generated during its reversible conversion [Fe(II)/Fe(III)]. The biosensor showed optimum response within 8 s at pH 5.0 and 30 °C. The linear working range for acrylamide was 3-90 nM, with a detection limit of 0.02 nM and sensitivity of 36.9 μA/nM/cm(2). The biosensor was evaluated and employed for determination of acrylamide in potato crisps.

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

Microfluidic approach of Sickled Cell Anemia

NASA Astrophysics Data System (ADS)

Abkarian, Manouk; Loiseau, Etienne; Massiera, Gladys

2012-11-01

Sickle Cell Anemia is a disorder of the microcirculation caused by a genetic point mutation that produces an altered hemoglobin protein called HbS. HbS self-assembles reversibly into long rope like fibers inside the red blood cells. The resulting distorded sickled red blood cells are believed to block the smallest capillaries of the tissues producing anemia. Despite the large amount of work that provided a thorough understanding of HbS polymerization in bulk as well as in intact red blood cells at rest, no consequent cellular scale approaches of the study of polymerization and its link to the capillary obstruction have been proposed in microflow, although the problem of obstruction is in essence a circulatory problem. Here, we use microfluidic channels, designed to mimic physiological conditions (flow velocity, oxygen concentration, hematocrit...) of the microcirculation to carry out a biomimetic study at the cellular scale of sickled cell vaso-occlusion. We show that flow geometry, oxygen concentration, white blood cells and free hemoglobin S are essential in the formation of original cell aggregates which could play a role in the vaso-occlusion events.

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 FACTOR DETERMINING THE SPREAD OF RED MARROW DURING ANEMIA

PubMed Central

McMaster, Philip D.; Haessler, Herbert

1921-01-01

Rabbits in which a chronic anemia of moderate grade is induced by repeated bleedings repair the hemoglobin loss much more rapidly when given subcutaneous injections of hemoglobin than when this is not the case. But the effect of the injections is not manifest for several weeks, during which many pale corpuscles are put out by the marrow; whence it follows that the introduced pigment does not find its way in quantity direct to the new-formed cells but must follow a more or less roundabout metabolic route, perhaps the same one as that of ordinary iron compounds destined for the blood. The rapid replacement of the circulating hemoglobin in the injected animals occurs chiefly through an increased production of corpuscular substance having the same color index as that found in uninjected, anemic controls. By color index in this connection is meant the relation of hemoglobin to the volume of the massed corpuscles. Late in the period of bleedings and hemoglobin injections the demand for stroma for the new-formed blood is far greater than in control animals that have been merely bled, yet the circulating corpuscles show no lessening in resistance to salt solution, such as might perhaps be expected were there a stroma lack. The hematopoietic tissue of the injected animals undergoes an extensive increase—a fact which speaks strongly for the view that the elements out of which stroma is formed are still abundant. The factor which determines the spread of red marrow during anemia is shown by our experiments to be the presence in the body of hemoglobin, or perhaps of its precursors, in excess of the amount which can be utilized by the marrow already existing. Numerous illustrations in support of the point can be adduced from human pathology. Two will suffice. The widespread "currant jelly" marrow of pernicious anemia is found in an organism rendered anemic but supplied with hemoglobin in excess; while the pale, restricted marrow of cases suffering from chronic anemia due to repeated hemorrhages is associated with depletion of the constituents necessary for pigment production. PMID:19868579

Role of Reversible Histidine Coordination in Hydroxylamine Reduction by Plant Hemoglobins (Phytoglobins).

PubMed

Athwal, Navjot Singh; Alagurajan, Jagannathan; Andreotti, Amy H; Hargrove, Mark S

2016-10-18

Reduction of hydroxylamine to ammonium by phytoglobin, a plant hexacoordinate hemoglobin, is much faster than that of other hexacoordinate hemoglobins or pentacoordinate hemoglobins such as myoglobin, leghemoglobin, and red blood cell hemoglobin. The reason for differences in reactivity is not known but could be intermolecular electron transfer between protein molecules in support of the required two-electron reduction, hydroxylamine binding, or active site architecture favoring the reaction. Experiments were conducted with phytoglobins from rice, tomato, and soybean along with human neuroglobin and soybean leghemoglobin that reveal hydroxylamine binding as the rate-limiting step. For hexacoordinate hemoglobins, binding is limited by the dissociation rate constant for the distal histidine, while leghemoglobin is limited by an intrinsically low affinity for hydroxylamine. When the distal histidine is removed from rice phytoglobin, a hydroxylamine-bound intermediate is formed and the reaction rate is diminished, indicating that the distal histidine imidazole side chain is critical for the reaction, albeit not for electron transfer but rather for direct interaction with the substrate. Together, these results demonstrate that phytoglobins are superior at hydroxylamine reduction because they have distal histidine coordination affinity constants near 1, and facile rate constants for binding and dissociation of the histidine side chain. Hexacoordinate hemoglobins such as neuroglobin are limited by tighter histidine coordination that blocks hydroxylamine binding, and pentacoordinate hemoglobins have intrinsically lower hydroxylamine affinities.

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

Hemoglobin Function in Stored Blood.

DTIC Science & Technology

1977-12-31

reverse aide if neceseary and Identify by block number) Blood preservation, Red Cell Function, 2,3- Diphosphoglycerate , Adenine, Inosine, Methylene Blue...2,3-DPG, pH, and glucose levels of whole blood and packed cells studied in CPD-adenine with the following variables: pH, glucose concentrations...aimed directly at maintaining red cell 2,3-DPG levels during blood storage in order for transfused blood to deliver oxygen to the tissues immediately

The effect of abnormal hemoglobins on the membrane regulation of cell hydration.

PubMed

Clark, M R; Shohet, S B

Several hemoglobinopathies are associated with abnormalities in the permeability of the red cell membrane, in some cases leading to permanent alterations of the intracellular milieu. Homozygous sickle cell disease is the most thoroughly studied example. Deoxygenation of sickle cells causes a transient increase in the permeability to monovalent cations and Ca; prolonged deoxygenation can lead to a permanent accumulation of Ca and loss of total cations and water. Although the mechanisms for the permeability changes are not yet defined, mechanical stress on the membrane, with subsequent damages by excess Ca or membrane-associated hemoglobin have been suggested to play a role. Loss of cell water and increase in mean cell hemoglobin concentration causes massive reduction of cell deformability in the oxygenated state and makes the hemoglobin more likely to undergo sickling because of the strong concentration dependence of the sickling process. Limited evidence suggests the occurrence of permeability defects in other hemoglobinopathies and the thalassemias. The suggested alterations range from a slight increase in K permeability of incubated thalassemia cells to substantial dehydration of cells from patients with homozygous hemoglobin C disease. Oxidative damage to the membrane, involving an abnormal hemoglobin-membrane association, may underly the permeability changes in these cells.

Clinical Factors and the Decision to Transfuse Chronic Dialysis Patients

PubMed Central

Whitman, Cynthia B.; Shreay, Sanatan; Gitlin, Matthew; van Oijen, Martijn G. H.

2013-01-01

Summary Background and objectives Red blood cell transfusion was previously the principle therapy for anemia in CKD but became less prevalent after the introduction of erythropoiesis-stimulating agents. This study used adaptive choice-based conjoint analysis to identify preferences and predictors of transfusion decision-making in CKD. Design, setting, participants, & measurements A computerized adaptive choice-based conjoint survey was administered between June and August of 2012 to nephrologists, internists, and hospitalists listed in the American Medical Association Masterfile. The survey quantified the relative importance of 10 patient attributes, including hemoglobin levels, age, occult blood in stool, severity of illness, eligibility for transplant, iron indices, erythropoiesis-stimulating agents, cardiovascular disease, and functional status. Triggers of transfusions in common dialysis scenarios were studied, and based on adaptive choice-based conjoint-derived preferences, relative importance by performing multivariable regression to identify predictors of transfusion preferences was assessed. Results A total of 350 providers completed the survey (n=305 nephrologists; mean age=46 years; 21% women). Of 10 attributes assessed, absolute hemoglobin level was the most important driver of transfusions, accounting for 29% of decision-making, followed by functional status (16%) and cardiovascular comorbidities (12%); 92% of providers transfused when hemoglobin was 7.5 g/dl, independent of other factors. In multivariable regression, Veterans Administration providers were more likely to transfuse at 8.0 g/dl (odds ratio, 5.9; 95% confidence interval, 1.9 to 18.4). Although transplant eligibility explained only 5% of decision-making, nephrologists were five times more likely to value it as important compared with non-nephrologists (odds ratio, 5.2; 95% confidence interval, 2.4 to11.1). Conclusions Adaptive choice-based conjoint analysis was useful in predicting influences on transfusion decisions. Hemoglobin level, functional status, and cardiovascular comorbidities most strongly influenced transfusion decision-making, but preference variations were observed among subgroups. PMID:23929931

The changes of red blood cell viscoelasticity and sports anemia in male 24-hr ultra-marathoners.

PubMed

Liu, Che-Hung; Tseng, Yen-Fang; Lai, Jiun-I; Chen, Yin-Quan; Wang, Shih-Hao; Kao, Wei-Fong; Li, Li-Hua; Chiu, Yu-Hui; How, Chorng-Kuang; Chang, Wen-Han

2018-05-01

In endurance sports, stress, dehydration and release of chemical factors have been associated with red blood cell (RBC) alterations of structure and function, which may contribute to sports anemia, a well-observed phenomenon during long-distance running. Until now, the investigation of the changes of viscoelastic properties of RBC membrane, a decisive factor of RBC deformability to avoid hemolysis, is lacking, especially in an Oriental population. nineteen runners were prospectively recruited into our study. Hematological parameters were analyzed before and immediately after the 2015 Taipei 24H Ultra-Marathon Festival, Taiwan. Video particle tracking microrheology was used to determine viscoelastic properties of each RBC sample by calculating the dynamic elastic modulus G'(f) and the viscous modulus G″(f) at frequency f = 20 Hz. Haptoglobin, RBC count, hemoglobin, hematocrit, mean cell hemoglobin, plasma free hemoglobin and unsaturated iron-binding capacity values of the recruited runners showed a statistically significant drop in the post-race values. Blood concentration of reticulocyte and ferritin were significantly higher at post-race compared with pre-race. 15 out of the 19 runners had a concurrent change in the elastic and the viscous moduli of their RBCs. Changes in the elastic and the viscous moduli were correlated with changes in the RBC count, hemoglobin and hematocrit. Viscoelasticity properties, the elastic modulus G'(f) and the viscous modulus G″(f) of RBCs are associated with endurance exercise-induced anemia. Copyright © 2017. Published by Elsevier Taiwan LLC.

ABO blood groups and malaria related clinical outcome.

PubMed

Deepa; Alwar, Vanamala A; Rameshkumar, Karuna; Ross, Cecil

2011-03-01

The study was undertaken to correlate the blood groups and clinical presentations in malaria patients and to understand the differential host susceptibility in malaria. From October 2007 to September 2008, malaria positive patients' samples were evaluated in this study. Hemoglobin, total leukocyte count, and platelet count of each patient were done on an automated cell counter. After determining the blood groups, malarial species and the severity of clinical course were correlated. A total of 100 patients were included in the study, of which 63 cases were positive for Plasmodium falciparum and 37 cases were positive for P. vivax infection and 11 patients had mixed infection. The results of the blood groups showed 22 - 'A' group, 42 - 'B' group, 35 - 'O' group and 1 was 'AB' group. When the clinical courses between different groups were compared using the following parameters for severe infection--a parasitic load of >10/1000 RBCs, severe anemia with hemoglobin < 6 g%, platelet count of <10,000/mm3, hepato or splenomegaly or clinical signs of severe malaria such as fever >101°F and other organ involvement, it was observed that 'O' group had an advantage over other the groups. The difference in rosetting ability between red blood cells of different 'ABO' blood groups with a diminished rosetting potential in blood group 'O' red blood cells was due to the differential host susceptibility. 'O' group had an advantage over the other three blood groups. Based on literature and the results of this study, the diminished rosetting potential in blood group 'O' red blood cells is suggested as the basis for the differential host susceptibility.

Study of smartphone suitability for mapping of skin chromophores

NASA Astrophysics Data System (ADS)

Kuzmina, Ilona; Lacis, Matiss; Spigulis, Janis; Berzina, Anna; Valeine, Lauma

2015-09-01

RGB (red-green-blue) technique for mapping skin chromophores by smartphones is proposed and studied. Three smartphones of different manufacturers were tested on skin phantoms and in vivo on benign skin lesions using a specially designed light source for illumination. Hemoglobin and melanin indices obtained by these smartphones showed differences in both tests. In vitro tests showed an increment of hemoglobin and melanin indices with the concentration of chromophores in phantoms. In vivo tests indicated higher hemoglobin index in hemangiomas than in nevi and healthy skin, and nevi showed higher melanin index compared to the healthy skin. Smartphones that allow switching off the automatic camera settings provided useful data, while those with "embedded" automatic settings appear to be useless for distant skin chromophore mapping.

Study of smartphone suitability for mapping of skin chromophores.

PubMed

Kuzmina, Ilona; Lacis, Matiss; Spigulis, Janis; Berzina, Anna; Valeine, Lauma

2015-09-01

RGB (red-green-blue) technique for mapping skin chromophores by smartphones is proposed and studied. Three smartphones of different manufacturers were tested on skin phantoms and in vivo on benign skin lesions using a specially designed light source for illumination. Hemoglobin and melanin indices obtained by these smartphones showed differences in both tests. In vitro tests showed an increment of hemoglobin and melanin indices with the concentration of chromophores in phantoms. In vivo tests indicated higher hemoglobin index in hemangiomas than in nevi and healthy skin, and nevi showed higher melanin index compared to the healthy skin. Smartphones that allow switching off the automatic camera settings provided useful data, while those with “embedded” automatic settings appear to be useless for distant skin chromophore mapping.

Evaluation of anemia diagnosis based on elastic light scattering (Conference Presentation)

NASA Astrophysics Data System (ADS)

Tong, Lieshu; Wang, Xinrui; Xie, Dengling; Chen, Xiaoya; Chu, Kaiqin; Dou, Hu; Smith, Zachary J.

2017-03-01

Currently, one-third of humanity is still suffering from anemia. In China the most common forms of anemia are iron deficiency and Thalassemia minor. Differentiating these two is the key to effective treatment. Iron deficiency is caused by malnutrition and can be cured by iron supplementation. Thalassemia is a hereditary disease in which the hemoglobin β chain is lowered or absent. Iron therapy is not effective, and there is evidence that iron therapy may be harmful to patients with Thalassemia. Both anemias can be diagnosed using red blood cell morphology: Iron deficiency presents a smaller mean cell volume compared to normal cells, but with a wide distribution; Thalassemia, meanwhile, presents a very small cell size and tight particle size distribution. Several researchers have proposed diagnostic indices based on red cell morphology to differentiate these two diseases. However, these indices lack sensitivity and specificity and are constructed without statistical rigor. Using multivariate methods we demonstrate a new classification method based on red cell morphology that diagnoses anemia in a Chinese population with enough accuracy for its use as a screening method. We further demonstrate a low cost instrument that precisely measures red cell morphology using elastic light scattering. This instrument is combined with an automated analysis program that processes scattering data to report red cell morphology without the need for user intervention. Despite using consumer-grade components, when comparing our experimental results with gold-standard measurements, the device can still achieve the high precision required for sensing clinically significant changes in red cell morphology.

Active nitric oxide produced in the red cell under hypoxic conditions by deoxyhemoglobin-mediated nitrite reduction.

PubMed

Nagababu, Enika; Ramasamy, Somasundaram; Abernethy, Darrell R; Rifkind, Joseph M

2003-11-21

Recent studies have generated a great deal of interest in a possible role for red blood cells in the transport of nitric oxide (NO) to the microcirculation and the vascular effect of this nitric oxide in facilitating the flow of blood through the microcirculation. Many questions have, however, been raised regarding such a mechanism. We have instead identified a completely new mechanism to explain the role of red cells in the delivery of NO to the microcirculation. This new mechanism results in the production of NO in the microcirculation where it is needed. Nitrite produced when NO reacts with oxygen in arterial blood is reutilized in the arterioles when the partial pressure of oxygen decreases and the deoxygenated hemoglobin formed reduces the nitrite regenerating NO. Nitrite reduction by hemoglobin results in a major fraction of the NO generated retained in the intermediate state where NO is bound to Hb(III) and in equilibrium with the nitrosonium cation bound to Hb(II). This pool of NO, unlike Hb(II)NO, is weakly bound and can be released from the heme. The instability of Hb(III)NO in oxygen and its displacement when flushed with argon requires that reliable determinations of red blood cell NO must be performed on freshly lysed samples without permitting the sample to be oxygenated. In fresh blood samples Hb(III)NO accounts for 75% of the red cell NO with appreciably higher values in venous blood than arterial blood. These findings confirm that nitrite reduction at reduced oxygen pressures is a major source for red cell NO. The formation and potential release from the red cell of this NO could have a major impact in regulating the flow of blood through the microcirculation.

Should modulation of p50 be a therapeutic target in the critically ill?

PubMed

Srinivasan, Amudan J; Morkane, Clare; Martin, Daniel S; Welsby, Ian J

2017-05-01

A defining feature of human hemoglobin is its oxygen binding affinity, quantified by the partial pressure of oxygen at which hemoglobin is 50% saturated (p50), and the variability of this parameter over a range of physiological and environmental states. Modulation of this property of hemoglobin can directly affect the degree of peripheral oxygen offloading and tissue oxygenation. Areas covered: This review summarizes the role of hemoglobin oxygen affinity in normal and abnormal physiology and discusses the current state of the literature regarding artificial modulation of p50. Hypoxic tumors, sickle cell disease, heart failure, and transfusion medicine are discussed in the context of recent advances in hemoglobin oxygen affinity manipulation. Expert commentary: Of particular clinical interest is the possibility of maintaining adequate end-organ oxygen availability in patients with anemia or compromised cardiac function via an increase in systemic p50. This increase in systemic p50 can be achieved with small molecule drugs or a packed red blood cell unit processing variant called rejuvenation, and human trials are needed to better understand the potential clinical benefits to modulating p50.

Method using CO for extending the useful shelf-life of refrigerated red blood cells

DOEpatents

Bitensky, Mark W.

1995-01-01

Method using CO for extending the useful shelf-life of refrigerated red blood cells. Carbon monoxide is utilized for stabilizing hemoglobin in red blood cells to be stored at low temperature. Changes observed in the stored cells are similar to those found in normal red cell aging in the body, the extent thereof being directly related to the duration of refrigerated storage. Changes in cell buoyant density, vesiculation, and the tendency of stored cells to bind autologous IgG antibody directed against polymerized band 3 IgG, all of which are related to red blood cell senescence and increase with refrigerated storage time, have been substantially slowed when red blood cells are treated with CO. Removal of the carbon monoxide from the red blood cells is readily and efficiently accomplished by photolysis in the presence of oxygen so that the stored red blood cells may be safely transfused into a recipient.

A mathematical and experimental simulation of the hematological response to weightlessness

NASA Technical Reports Server (NTRS)

Kimzey, S. L.; Leonard, J. I.; Johnson, P. C.

1979-01-01

A mathematical model of erythropoiesis control was used to simulate the effects of bedrest and zero-g on the circulating red cell mass. The model incorporates the best current understanding of the dynamics of red cell production and destruction and the associated feedback regulation. Specifically studied were the hemodynamic responses of a 28-day bedrest study devised to simulate Skylab experience. The results support the hypothesis that red cell loss during supine bedrest is a normal physiological feedback process in response to hemoconcentration enhanced tissue oxygenation and suppression of red cell production. Model simulation suggested the possibilities that this period was marked by some combination of increased oxygen-hemoglobin affinity, small reduction in mean red cell life span, ineffective erythropoiesis, or abnormal reticulocytosis.

High incidence of 3-thalassemia, hemoglobin E, and glucose-6-phosphate dehydrogenase deficiency in populations of malaria-endemic southern Shan State, Myanmar.

PubMed

Than, Aung Myint; Harano, Teruo; Harano, Keiko; Myint, Aye Aye; Ogino, Tetsuya; Okadaa, Shigeru

2005-08-01

Samples from 916 members of various ethnic groups from malaria-endemic southern Shan State, Myanmar, were analyzed for 3-thalassemia (3-thal), 3-thalassemia (3-thal), abnormal hemoglobin variants, and glucose-6-phosphate dehydrogenase (G6PD) deficiency. Of these subjects, 530 (57.9%) were found to have at least one of these red cell genetic disorders. The overall frequencies for the various red cell genetic disorders were as follows: 3-thal, 37.5% (343/916); hemoglobin E (Hb-E), 20.3% (186/916); G6PD-Mahidol, 17.5% (160/916); and 3-thal, 0.3% (3/916). The frequencies of combined disorders were 6.9% (63/ 916) for 3-thal/Hb-E, 5.7% (52/916) for 3-thal/G6PD-Mahidol, 2.8% (26/916) for Hb-E/G6PD-Mahidol, 1.1% (10/916) for 3-thal/Hb-E/G6PD-Mahidol, and 0.1% (1/916) for 3-thal/3-thal/G6PD-Mahidol. Of the various ethnic and non-ethnic groups, the Bamar population showed the highest frequencies of 3-thal (56.9%, 177/311), Hb-E (28.3%, 88/311), and G6PD-Mahidol (21.2%, 66/311) (all duplicated and triplicated cases were included). In addition, 2 new mutations, an 3 gene triplication (/333(anti3.7); 0.2%, 2/916) and Hb-Neapolis (0.1%, 1/916), were detected. Our results showed that race was the dominant factor affecting the frequencies of red cell genetic disorders in malaria-endemic areas of Myanmar.

Effect of Packed Red Blood Cell Cryopreservation on Development of the Storage Lesion and Inflammation

DTIC Science & Technology

2015-09-01

Scientific International Inc., Hampton, NH) at 22°C. Lactic acid (LA) and cell free potassium (K+) were measured using point of care clinical blood...equilibrium maintained by adenosine triphosphate (ATP) dependent potassium pumps [17]. Lactic acid accumulation was more pronounced in the first 21 days...Hct hematocrit Hgb hemoglobin K+ cell free potassium LA lactic acid pRBC packed red blood cell PS phosphatidylserine

Previous cryopreservation alters the natural history of the red blood cell storage lesion

PubMed Central

Chang, Alex L.; Hoehn, Richard S.; Jernigan, Peter; Cox, Daniel; Schreiber, Martin; Pritts, Timothy A.

2016-01-01

Background During storage, packed red blood cells (pRBCs) undergo a number of biochemical, metabolic and morphologic changes, collectively known as the “storage lesion”. We aimed to determine the effect of cryopreservation on the red blood cell storage lesion compared to traditional 4°C storage. Methods Previously cryopreserved human packed red blood cells were compared to age matched never frozen packed red blood cells obtained from the local blood bank. The development of the red cell storage lesion was evaluated after 7, 14, 21, 28, and 42 days of storage at 4°C in AS-3 storage medium. We measured physiological parameters including cell counts, lactic acid and potassium concentrations as well as signs of eryptosis including loss of phosphatidylserine (PS) asymmetry, microparticle production and osmotic fragility in hypotonic saline. Results Compared to controls, previously cryopreserved pRBC at 7 days of storage in AS-3 showed lower red cell counts (3.7 vs 5.3 ×10^6 cells/uL, p(<0.01), hemoglobin (12.0 vs 16.5 g/dL, p<0.01), hematocrit (33.0 vs 46.5%, p<0.01), and pH (6.27 vs 6.72, p<0.01). Over 28 days of storage, storage cryopreserved pRBC developed increased cell free hemoglobin (0.7 vs 0.3 g/dL, p<0.01), greater PS exposure (10.1 vs 3.3%, p<0.01), and microparticle production (30,836 vs 1,802 MP/uL, p<0.01). Previously cryopreserved cells were also less resistant to osmotic stress. Conclusion The red blood cell storage lesion is accelerated in previously cryopreserved pRBC after thawing. Biochemical deterioration of thawed and deglycerolized red cells suggests that storage time prior to transfusion should be limited in order to achieve similar risk profiles as never frozen standard liquid storage pRBC units. PMID:27380532

Gene Therapy in Patients with Transfusion-Dependent β-Thalassemia.

PubMed

Thompson, Alexis A; Walters, Mark C; Kwiatkowski, Janet; Rasko, John E J; Ribeil, Jean-Antoine; Hongeng, Suradej; Magrin, Elisa; Schiller, Gary J; Payen, Emmanuel; Semeraro, Michaela; Moshous, Despina; Lefrere, Francois; Puy, Hervé; Bourget, Philippe; Magnani, Alessandra; Caccavelli, Laure; Diana, Jean-Sébastien; Suarez, Felipe; Monpoux, Fabrice; Brousse, Valentine; Poirot, Catherine; Brouzes, Chantal; Meritet, Jean-François; Pondarré, Corinne; Beuzard, Yves; Chrétien, Stany; Lefebvre, Thibaud; Teachey, David T; Anurathapan, Usanarat; Ho, P Joy; von Kalle, Christof; Kletzel, Morris; Vichinsky, Elliott; Soni, Sandeep; Veres, Gabor; Negre, Olivier; Ross, Robert W; Davidson, David; Petrusich, Alexandria; Sandler, Laura; Asmal, Mohammed; Hermine, Olivier; De Montalembert, Mariane; Hacein-Bey-Abina, Salima; Blanche, Stéphane; Leboulch, Philippe; Cavazzana, Marina

2018-04-19

Donor availability and transplantation-related risks limit the broad use of allogeneic hematopoietic-cell transplantation in patients with transfusion-dependent β-thalassemia. After previously establishing that lentiviral transfer of a marked β-globin (β A-T87Q ) gene could substitute for long-term red-cell transfusions in a patient with β-thalassemia, we wanted to evaluate the safety and efficacy of such gene therapy in patients with transfusion-dependent β-thalassemia. In two phase 1-2 studies, we obtained mobilized autologous CD34+ cells from 22 patients (12 to 35 years of age) with transfusion-dependent β-thalassemia and transduced the cells ex vivo with LentiGlobin BB305 vector, which encodes adult hemoglobin (HbA) with a T87Q amino acid substitution (HbA T87Q ). The cells were then reinfused after the patients had undergone myeloablative busulfan conditioning. We subsequently monitored adverse events, vector integration, and levels of replication-competent lentivirus. Efficacy assessments included levels of total hemoglobin and HbA T87Q , transfusion requirements, and average vector copy number. At a median of 26 months (range, 15 to 42) after infusion of the gene-modified cells, all but 1 of the 13 patients who had a non-β 0 /β 0 genotype had stopped receiving red-cell transfusions; the levels of HbA T87Q ranged from 3.4 to 10.0 g per deciliter, and the levels of total hemoglobin ranged from 8.2 to 13.7 g per deciliter. Correction of biologic markers of dyserythropoiesis was achieved in evaluated patients with hemoglobin levels near normal ranges. In 9 patients with a β 0 /β 0 genotype or two copies of the IVS1-110 mutation, the median annualized transfusion volume was decreased by 73%, and red-cell transfusions were discontinued in 3 patients. Treatment-related adverse events were typical of those associated with autologous stem-cell transplantation. No clonal dominance related to vector integration was observed. Gene therapy with autologous CD34+ cells transduced with the BB305 vector reduced or eliminated the need for long-term red-cell transfusions in 22 patients with severe β-thalassemia without serious adverse events related to the drug product. (Funded by Bluebird Bio and others; HGB-204 and HGB-205 ClinicalTrials.gov numbers, NCT01745120 and NCT02151526 .).

Dynamics of erythrocyte count, hemoglobin, and catalase activity in rat blood in hypokinesia, muscular activity and restoration

NASA Technical Reports Server (NTRS)

Taneyeva, G. V.; Potapovich, G. M.; Voloshko, N. A.; Uteshev, A. B.

1980-01-01

Tests were conducted to prove that muscular exertion (in this instance swimming) of different duration and intensity, as well as hypodynamia, result in an increase of hemoglobin and number of red blood cells in peripheral blood rats. Catalase activity increased with an increase in the duration of swimming, but only up to 6 hr; with 7-9 hr of swimming as well as in hypodynamia, catalase activity decreased. It was also observed that under hypodynamia as well as in 3, 5 and 6 hr exertion (swimming) the color index of blood decreased. Pressure chamber treatment (for 8 min each day for one week), alternating a 2 min negative pressure up to 35 mm Hg with 1 min positive pressure, increased the erythrocyte count and hemoglobin content.

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

Hemoglobin consumption by P. falciparum in individual erythrocytes imaged via quantitative phase spectroscopy

NASA Astrophysics Data System (ADS)

Rinehart, Matthew T.; Park, Han Sang; Walzer, Katelyn A.; Chi, Jen-Tsan Ashley; Wax, Adam

2016-04-01

Plasmodium falciparum infection causes structural and biochemical changes in red blood cells (RBCs). To quantify these changes, we apply a novel optical technique, quantitative phase spectroscopy (QPS) to characterize individual red blood cells (RBCs) during the intraerythrocytic life cycle of P. falciparum. QPS captures hyperspectral holograms of individual RBCs to measure spectroscopic changes across the visible wavelength range (475-700 nm), providing complex information, i.e. amplitude and phase, about the light field which has interacted with the cell. The complex field provides complimentary information on hemoglobin content and cell mass, which are both found to dramatically change upon infection by P. falciparum. Hb content progressively decreases with parasite life cycle, with an average 72.2% reduction observed for RBCs infected by schizont-stage P. falciparum compared to uninfected cells. Infection also resulted in a 33.1% reduction in RBC’s optical volume, a measure of the cells’ non-aqueous components. Notably, optical volume is only partially correlated with hemoglobin content, suggesting that changes in other dry mass components such as parasite mass may also be assessed using this technique. The unique ability of QPS to discriminate individual healthy and infected cells using spectroscopic changes indicates that the approach can be used to detect disease.

Cellular function reinstitution of offspring red blood cells cloned from the sickle cell disease patient blood post CRISPR genome editing.

PubMed

Wen, Jianguo; Tao, Wenjing; Hao, Suyang; Zu, Youli

2017-06-13

Sickle cell disease (SCD) is a disorder of red blood cells (RBCs) expressing abnormal hemoglobin-S (HbS) due to genetic inheritance of homologous HbS gene. However, people with the sickle cell trait (SCT) carry a single allele of HbS and do not usually suffer from SCD symptoms, thus providing a rationale to treat SCD. To validate gene therapy potential, hematopoietic stem cells were isolated from the SCD patient blood and treated with CRISPR/Cas9 approach. To precisely dissect genome-editing effects, erythroid progenitor cells were cloned from single colonies of CRISPR-treated cells and then expanded for simultaneous gene, protein, and cellular function studies. Genotyping and sequencing analysis revealed that the genome-edited erythroid progenitor colonies were converted to SCT genotype from SCD genotype. HPLC protein assays confirmed reinstallation of normal hemoglobin at a similar level with HbS in the cloned genome-edited erythroid progenitor cells. For cell function evaluation, in vitro RBC differentiation of the cloned erythroid progenitor cells was induced. As expected, cell sickling assays indicated function reinstitution of the genome-edited offspring SCD RBCs, which became more resistant to sickling under hypoxia condition. This study is an exploration of genome editing of SCD HSPCs.

Physiological Effects of Continuous Colored Light Exposure on Mayer Wave Activity in Cerebral Hemodynamics: A Functional Near-Infrared Spectroscopy (fNIRS) Study.

PubMed

Metz, A J; Klein, S D; Scholkmann, F; Wolf, U

2017-01-01

We are increasingly exposed to colored light, but its impact on human physiology is not yet extensively investigated. In the present study we aimed to determine the effects of colored light on human cerebral Mayer wave activity (MWA). We measured oxy- ([O 2 Hb]), deoxy- ([HHb]), total hemoglobin ([tHb]) concentrations and tissue oxygen saturation (StO 2 ) by functional near-infrared spectroscopy (fNIRS) in the left and right pre-frontal cortex (L-PFC, R-PFC) of 17 subjects (median age: 29 years, 6 women). In a randomized crossover design subjects were exposed to blue, red, green, and yellow LED light for 10 min. Pre-light (8 min, baseline) and post-light (15 min, recovery) conditions were darkness. MWA was calculated from band-pass filtered fNIRS signals (~0.08-0.12 Hz). The medians from the last 3 min of each period (baseline, light exposure, recovery) were statistically analyzed. MWA was increased during red and green light vs. baseline and after blue light exposure in recovery in the L-PFC. MWA differed depending on the chosen frequency range, filter design, and type of signals to analyze (raw intensity, hemoglobin signal from multi-distance method or modified Beer-Lambert law, or within hemoglobin signals).

Effects of formalin fixation on tissue optical properties of in-vitro brain samples

NASA Astrophysics Data System (ADS)

Anand, Suresh; Cicchi, Riccardo; Martelli, Fabrizio; Giordano, Flavio; Buccoliero, Anna Maria; Guerrini, Renzo; Pavone, Francesco S.

2015-03-01

Application of light spectroscopy based techniques for the detection of cancers have emerged as a promising approach for tumor diagnostics. In-vivo or freshly excised samples are normally used for point spectroscopic studies. However, ethical issues related to in-vivo studies, rapid decay of surgically excised tissues and sample availability puts a limitation on in-vivo and in-vitro studies. There has been a few studies reported on the application of formalin fixed samples with good discrimination capability. Usually formalin fixation is performed to prevent degradation of tissues after surgical resection. Fixing tissues in formalin prevents cell death by forming cross-linkages with proteins. Previous investigations have revealed that washing tissues fixed in formalin using phosphate buffered saline is known to reduce the effects of formalin during spectroscopic measurements. But this could not be the case with reflectance measurements. Hemoglobin is a principal absorbing medium in biological tissues in the visible range. Formalin fixation causes hemoglobin to seep out from red blood cells. Also, there could be alterations in the refractive index of tissues when fixed in formalin. In this study, we propose to investigate the changes in tissue optical properties between freshly excised and formalin fixed brain tissues. The results indicate a complete change in the spectral profile in the visible range where hemoglobin has its maximum absorption peaks. The characteristic bands of oxy-hemoglobin at 540, 580 nm and deoxy-hemoglobin at 555 nm disappear in the case of samples fixed in formalin. In addition, an increased spectral intensity was observed for the wavelengths greater than 650 nm where scattering phenomena are presumed to dominate.

Hemoglobin stability: observations on the denaturation of normal and abnormal hemoglobins by oxidant dyes, heat, and alkali

PubMed Central

Rieder, Ronald F.

1970-01-01

Several unstable mutant hemoglobins have alterations which affect areas of the molecule involved in the attachment of heme to globin. Loss of heme from globin has been demonstrated during the denaturation of some of these unstable mutants. The importance of heme ligands for the stability of hemoglobin was illustrated in the present experiments on the denaturation of several hemoglobins and hemoglobin derivatives by heat, oxidative dyes, and alkali. Heating of normal hemolysates diluted to 4 g of hemoglobin per 100 ml at 50°C for 20 hr in 0.05 M sodium phosphate, pH 7.4, caused precipitation of 23-54% of the hemoglobin. Dialysis against water or dilution of the sample decreased denaturation to 12-20%. Precipitation was decreased to less than 3.5% by the presence of 0.015 M potassium cyanide. Increasing the ionic strength of the medium increased precipitation. Cyanide prevented the formation of inclusion bodies when red cells containing unstable hemoglobin Philly, β35 tyr → phe, were incubated with the redox dye new methylene blue. Conversion to methemoglobin increased the rate of alkali denaturation of hemoglobin but the presence of potassium cyanide returned the denaturation rate to that of ferrohemoglobin. The ability of cyanide to decrease heat precipitation of hemoglobin may depend on a dimeric or tetrameric state of the hemoglobin molecule. Purified β-chains, which exist as tetramers, were stabilized but purified monomeric α-chains were not rendered more heat resistant by the ligand. Stabilization of hemoglobin by cyanide required binding of the ligand to only one heme of an αβ-dimer. Hemoglobin Gun Hill, an unstable molecule with heme groups present only on the α-chains was quite heat stable in the presence of cyanide. The binding of cyanide to the iron atom in methemoglobin is thought to be associated with increased planarity of the heme group and increased stability of the heme-globin complex. The stabilizing effect of cyanide in the above experiments suggests that Heinz body formation, heat precipitation of hemoglobin, and the increased alkali denaturation of methemoglobin depend on changes of heme-globin binding. Images PMID:5480860

Fluorescent measurements in whole blood and plasma using red-emitting dyes

NASA Astrophysics Data System (ADS)

Abugo, Omoefe O.; Herman, Petr; Lakowicz, Joseph R.

2000-04-01

We have determined the fluorescence characteristics of albumin blue 670 and Rhodamine 800 in plasma and blood in order to test the feasibility of making direct fluorescence sensing measurements in blood. These dyes were used because of their absorption in the red/NIR where absorption by hemoglobin is minimized. Front face illumination and detection was used to minimize absorption and scattering during measurement. Fluorescence emission was observed for these dyes in plasma and blood. Attenuation of the fluorescence emission was observed in blood because of hemoglobin absorption. Using frequency domain fluorometry, we recovered the expected lifetime parameters for both dyes in blood and plasma. We were able to quantify HSA concentrations using changes in the mean lifetime of AB670, a dye previously shown to bind preferentially to HSA. Rh800 concentrations in plasma and blood were also determined using modulation sensing. Anisotropy measurements revealed high Anisotropy for these dyes in plasma and blood. It also showed an increase in the anisotropy of AB670 with increase in HSA concentration in the presence of red blood cells. These results indicate that qualitative and quantitative fluorescence measurements can be made directly in blood without the need to process the blood.

Numbers, Neurons and Tides, Oh My!

ERIC Educational Resources Information Center

Ortiz, Mary Theresa

2006-01-01

Mathematical applications to biology are presented in Anatomy & Physiology, General and Marine Biology. Body measurements and anatomical terminology are integrated, and problems involving neuron conduction speed, red blood cells, hemoglobin and glomerular filtration presented. General Biology applications include trans-membrane potential and…

Associations between blood BTEXS concentrations and hematologic parameters among adult residents of the U.S. Gulf States.

PubMed

Doherty, Brett T; Kwok, Richard K; Curry, Matthew D; Ekenga, Christine; Chambers, David; Sandler, Dale P; Engel, Lawrence S

2017-07-01

Studies of workers exposed to benzene at average air concentrations below one part per million suggest that benzene, a known hematotoxin, causes hematopoietic damage even at low exposure levels. However, evidence of such effects outside of occupational settings and for other volatile organic compounds (VOCs) is limited. To investigate associations between ambient exposures to five VOCs, including benzene, and hematologic parameters among adult residents of the U.S. Gulf Coast. Blood concentrations of selected VOCs were measured in a sample of adult participants in the Gulf Long-term Follow-up Study (GuLF STUDY) during 2012 and 2013. Complete blood counts with differentials were also performed on a subset of participants (n=406). We used these data together with detailed questionnaire data to estimate adjusted associations between blood BTEXS (benzene, toluene, ethylbenzene, o-xylene, m/p-xylene, and styrene) concentrations and hematologic parameters using generalized linear models. We observed inverse associations between blood benzene concentrations and hemoglobin concentration and mean corpuscular hemoglobin concentration, and a positive association with red cell distribution width among tobacco smoke-unexposed participants (n=146). Among tobacco smoke-exposed participants (n=247), we observed positive associations between blood VOC concentrations and several hematologic parameters, including increased white blood cell and platelet counts, suggestive of hematopoietic stimulation typically associated with tobacco smoke exposure. Most associations were stronger for benzene than for the other VOCs. Our results suggest that ambient exposure to BTEXS, particularly benzene, may be associated with hematologic effects, including decreased hemoglobin concentration, mean corpuscular hemoglobin concentration, and increased red cell distribution width. Published by Elsevier Inc.

Far red/near infrared light-induced cardioprotection under normal and diabetic conditions

NASA Astrophysics Data System (ADS)

Keszler, Agnes; Baumgardt, Shelley; Hwe, Christopher; Bienengraeber, Martin

2015-03-01

Far red/near infrared light (NIR) is beneficial against cardiac ischemia and reperfusion injury (I/R), although the exact underlying mechanism is unknown. Previously we established that NIR enhanced the cardioprotective effect of nitrite in the rabbit heart. Furthermore, we observed that the nitrosyl myoglobin (MbNO) level in ischemic tissue decreased upon irradiation of the heart. Our hypothesis was that protection against I/R is dependent on nitric oxide (NO)-release from heme-proteins, and remains present during diabetes. When mice were subjected to I/R NIR (660 nm) applied during the beginning of reperfusion reduced infarct size dose dependently compared to untreated animals. Similarly, the isolated (Langendorff) heart model resulted in sustained left ventricular diastolic pressure after I/R in NIR-treated hearts. NIRinduced protection was preserved in a diabetic mouse model (db/db) and during acute hyperglycemia. NIR liberated NO from nitrosyl hemoglobin (HbNO) and MbNO as well as from HbNO isolated from the blood of diabetic animals. In the Langendorff model, after application of the nitrosylated form of a hemoglobin-based oxygen carrier as an NO donor NIR induced an increase in NADH level, suggesting a mild inhibition of mitochondrial respiration by NO during reperfusion. Taken together, NIR applied during reperfusion protects the myocardium against I/R in a NO-dependent and mitochondrion-targeted manner. This unique mechanism is conserved under diabetic conditions where other protective strategies fail.

Mature red blood cells: from optical model to inverse light-scattering problem.

PubMed

Gilev, Konstantin V; Yurkin, Maxim A; Chernyshova, Ekaterina S; Strokotov, Dmitry I; Chernyshev, Andrei V; Maltsev, Valeri P

2016-04-01

We propose a method for characterization of mature red blood cells (RBCs) morphology, based on measurement of light-scattering patterns (LSPs) of individual RBCs with the scanning flow cytometer and on solution of the inverse light-scattering (ILS) problem for each LSP. We considered a RBC shape model, corresponding to the minimal bending energy of the membrane with isotropic elasticity, and constructed an analytical approximation, which allows rapid simulation of the shape, given the diameter and minimal and maximal thicknesses. The ILS problem was solved by the nearest-neighbor interpolation using a preliminary calculated database of 250,000 theoretical LSPs. For each RBC in blood sample we determined three abovementioned shape characteristics and refractive index, which also allows us to calculate volume, surface area, sphericity index, spontaneous curvature, hemoglobin concentration and content.

Mature red blood cells: from optical model to inverse light-scattering problem

PubMed Central

Gilev, Konstantin V.; Yurkin, Maxim A.; Chernyshova, Ekaterina S.; Strokotov, Dmitry I.; Chernyshev, Andrei V.; Maltsev, Valeri P.

2016-01-01

We propose a method for characterization of mature red blood cells (RBCs) morphology, based on measurement of light-scattering patterns (LSPs) of individual RBCs with the scanning flow cytometer and on solution of the inverse light-scattering (ILS) problem for each LSP. We considered a RBC shape model, corresponding to the minimal bending energy of the membrane with isotropic elasticity, and constructed an analytical approximation, which allows rapid simulation of the shape, given the diameter and minimal and maximal thicknesses. The ILS problem was solved by the nearest-neighbor interpolation using a preliminary calculated database of 250,000 theoretical LSPs. For each RBC in blood sample we determined three abovementioned shape characteristics and refractive index, which also allows us to calculate volume, surface area, sphericity index, spontaneous curvature, hemoglobin concentration and content. PMID:27446656

A Novel Automated Slide-Based Technology for Visualization, Counting, and Characterization of the Formed Elements of Blood: A Proof of Concept Study.

PubMed

Winkelman, James W; Tanasijevic, Milenko J; Zahniser, David J

2017-08-01

- A novel automated slide-based approach to the complete blood count and white blood cell differential count is introduced. - To present proof of concept for an image-based approach to complete blood count, based on a new slide preparation technique. A preliminary data comparison with the current flow-based technology is shown. - A prototype instrument uses a proprietary method and technology to deposit a precise volume of undiluted peripheral whole blood in a monolayer onto a glass microscope slide so that every cell can be distinguished, counted, and imaged. The slide is stained, and then multispectral image analysis is used to measure the complete blood count parameters. Images from a 600-cell white blood cell differential count, as well as 5000 red blood cells and a variable number of platelets, that are present in 600 high-power fields are made available for a technologist to view on a computer screen. An initial comparison of the basic complete blood count parameters was performed, comparing 1857 specimens on both the new instrument and a flow-based hematology analyzer. - Excellent correlations were obtained between the prototype instrument and a flow-based system. The primary parameters of white blood cell, red blood cell, and platelet counts resulted in correlation coefficients (r) of 0.99, 0.99, and 0.98, respectively. Other indices included hemoglobin (r = 0.99), hematocrit (r = 0.99), mean cellular volume (r = 0.90), mean corpuscular hemoglobin (r = 0.97), and mean platelet volume (r = 0.87). For the automated white blood cell differential counts, r values were calculated for neutrophils (r = 0.98), lymphocytes (r = 0.97), monocytes (r = 0.76), eosinophils (r = 0.96), and basophils (r = 0.63). - Quantitative results for components of the complete blood count and automated white blood cell differential count can be developed by image analysis of a monolayer preparation of a known volume of peripheral blood.

Coinheritance of hemoglobin D-Punjab and β0-thalassemia 3.4 kb deletion in a Thai girl

PubMed Central

Panyasai, Sitthichai; Rahad, Sarinna; Pornprasert, Sakorn

2017-01-01

Hemoglobin (Hb) D. Punjab [β121(GH4) Glu→Gln; HBB: C.364G>C] and β0-thalassemia 3.4 kb deletion are very rare in the Thai population. For the first time, the coinheritance of HbD-Punjab with β0-thalassemia 3.4 kb deletion was reported in a 7-year-old Thai girl. She had mild anemia (Hb 115.0 g/L and mean corpuscular hemoglobin 18.1 pg) with red blood cell microcytosis (mean corpuscular volume 52.5 fL). By capillary electrophoresis (CE), HbD-Punjab was found at a migration position of 180 s with the value of 81.9% while the level of HbA2 was 7.3%. Based on the elevated HbA2, the molecular analysis for detection of β0-thalassemia mutations was performed. The 490 bp amplified fragments from β0-thalassemia 3.4 kb deletion was observed. Thus, the coinheritance of HbD-Punjab with β0-thalassemia can be found in the Thai population. The HbA2 measured on CE is a reliable parameter for differentiating the homozygote of HbD-Punjab and compound heterozygote of HbD-Punjab and β0-thalassemia. PMID:28970692

Aryloxyalkanoic Acids as Non-Covalent Modifiers of the Allosteric Properties of Hemoglobin

PubMed Central

Omar, Abdelsattar M.; Mahran, Mona A.; Ghatge, Mohini S.; Bamane, Faida H. A.; Ahmed, Mostafa H.; El-Araby, Moustafa E.; Abdulmalik, Osheiza; Safo, Martin K.

2017-01-01

Hemoglobin (Hb) modifiers that stereospecifically inhibit sickle hemoglobin polymer formation and/or allosterically increase Hb affinity for oxygen have been shown to prevent the primary pathophysiology of sickle cell disease (SCD), specifically, Hb polymerization and red blood cell sickling. Several such compounds are currently being clinically studied for the treatment of SCD. Based on the previously reported non-covalent Hb binding characteristics of substituted aryloxyalkanoic acids that exhibited antisickling properties, we designed, synthesized and evaluated 18 new compounds (KAUS II series) for enhanced antisickling activities. Surprisingly, select test compounds showed no antisickling effects or promoted erythrocyte sickling. Additionally, the compounds showed no significant effect on Hb oxygen affinity (or in some cases, even decreased the affinity for oxygen). The X-ray structure of deoxygenated Hb in complex with a prototype compound, KAUS-23, revealed that the effector bound in the central water cavity of the protein, providing atomic level explanations for the observed functional and biological activities. Although the structural modification did not lead to the anticipated biological effects, the findings provide important direction for designing candidate antisickling agents, as well as a framework for novel Hb allosteric effectors that conversely, decrease the protein affinity for oxygen for potential therapeutic use for hypoxic- and/or ischemic-related diseases. PMID:27529207

Energy metabolism and hematology of white-tailed deer fawns

USGS Publications Warehouse

Rawson, R.E.; DelGiudice, G.D.; Dziuk, H.E.; Mech, L.D.

1992-01-01

Resting metabolic rates, weight gains and hematologic profiles of six newborn, captive white-tailed deer (Odocoileus virginianus) fawns (four females, two males) were determined during the first 3 mo of life. Estimated mean daily weight gain of fawns was 0.2 kg. The regression equation for metabolic rate was: Metabolic rate (kcal/kg0.75/day) = 56.1 +/- 1.3 (age in days), r = 0.65, P less than 0.001). Regression equations were also used to relate age to red blood cell count (RBC), hemoglobin concentration (Hb), packed cell volume, white blood cell count, mean corpuscular volume, mean corpuscular hemoglobin concentration (MCHC), and mean corpuscular hemoglobin. The age relationships of Hb, MCHC, and smaller RBC's were indicative of an increasing and more efficient oxygen-carrying and exchange capacity to fulfill the increasing metabolic demands for oxygen associated with increasing body size.

Method using CO for extending the useful shelf-life of refrigerated red blood cells

DOEpatents

Bitensky, M.W.

1995-12-19

A method is disclosed using CO for extending the useful shelf-life of refrigerated red blood cells. Carbon monoxide is utilized for stabilizing hemoglobin in red blood cells to be stored at low temperature. Changes observed in the stored cells are similar to those found in normal red cell aging in the body, the extent thereof being directly related to the duration of refrigerated storage. Changes in cell buoyant density, vesiculation, and the tendency of stored cells to bind autologous IgG antibody directed against polymerized band 3 IgG, all of which are related to red blood cell senescence and increase with refrigerated storage time, have been substantially slowed when red blood cells are treated with CO. Removal of the carbon monoxide from the red blood cells is readily and efficiently accomplished by photolysis in the presence of oxygen so that the stored red blood cells may be safely transfused into a recipient. 5 figs.

Thrombotic thrombocytopenic purpura and sickle cell crisis.

PubMed

Shelat, Suresh G

2010-04-01

Described is a case of acute chest syndrome in a sickle-cell patient (hemoglobin SS) who also developed signs and symptoms of thrombotic thrombocytopenic purpura, including thrombocytopenia and hemolysis (anemia, elevated lactate dehydrogenase, presence of schistocytes, dark-colored plasma, and elevations in nucleated red blood cells). The ADAMTS13 activity level was normal. Discussed are the diagnosis and therapeutic management issues and the challenges of differentiating the vasoocclusive and hemolytic complications of sickling red blood cells from the thrombotic microangiopathy of thrombotic thrombocytopenic purpura.

Small-angle X-ray scattering probe of intermolecular interaction in red blood cells

NASA Astrophysics Data System (ADS)

Liu, Guan-Fen; Wang, We-Jia; Xu, Jia-Hua; Dong, Yu-Hui

2015-03-01

With high concentrations of hemoglobin (Hb) in red blood cells, self-interactions among these molecules could increase the propensities of their polymerization and aggregation. In the present work, high concentration Hb in solution and red blood cells were analyzed by small-angle X-ray scattering. Calculation of the effective structure factor indicates that the interaction of Hb molecules is the same when they are crowded together in both the cell and physiological saline. The Hb molecules stay individual without the formation of aggregates and clusters in cells. Supported by National Basic Research Program of China (2009CB918600) and National Natural Science Foundation of China (10979005)

The influence of water versus carbohydrate-electrolyte hydration on blood components during a 16-km military march.

PubMed

de Carvalho, Moisés Vieira; Marins, João Carlos Bouzas; Silami-Garcia, Emerson

2007-01-01

The purpose of this study was to identify and to compare the effects of ingesting liquids during a 16-km military march under moderate environmental conditions. Twenty-six volunteer male subjects were randomly divided into two groups. Group GW received water (n=12), and group GP received an electrolytic carbohydrate solution (n=14). Blood and urine samples were obtained immediately before and after the march. No significant differences between the drinks were found for any of the measured variables. However, important results (p < 0.05) were observed by comparing variables before and after exercise. The variables included sodium, hematocrit, red blood cell, hemoglobin, and lactic acid levels and body weight (group GW) and sodium, potassium, hematocrit, red blood cell, hemoglobin, and lactic acid levels (group GP). Under the environmental conditions and hydration procedures applied, the results of this study showed similarities in the behavior of the variables, regardless of the kind of beverage consumed.

Formation of hemoglobin photoproduct is responsible for two-photon and single photon-excited fluorescence of red blood cells

NASA Astrophysics Data System (ADS)

Shirshin, Evgeny A.; Yakimov, Boris P.; Rodionov, Sergey A.; Omelyanenko, Nikolai P.; Priezzhev, Alexander V.; Fadeev, Victor V.; Lademann, Juergen; Darvin, Maxim E.

2018-07-01

Two-photon excited fluorescence of red blood cells (RBC) has been reported to be applicable for their assessment in vitro and in vivo. The corresponding fluorescence emission was ascribed to hemoglobin (Hb), however, as Hb is essentially non-fluorescent at single-photon excitation, the mechanism of two-photon excited fluorescence of RBC remains debatable. Here we show that a fluorescent photoproduct, characterized by an ultrafast decay of excitation, is formed after irradiation of Hb with femtosecond laser pulses with ca. 8 · 10‑5 quantum yield, and that it is also fluorescent at single-photon excitation. The formation of a similar photoproduct was also shown for Hb continuous wave irradiation with blue light with ca. 10‑5 formation quantum yield. The kinetics of the Hb photoproduct formation and its spectral properties were investigated. The obtained results clarify the processes responsible for RBC fluorescence observed in two-photon microscopy experiments.

Using digital inpainting to estimate incident light intensity for the calculation of red blood cell oxygen saturation from microscopy images.

PubMed

Sové, Richard J; Drakos, Nicole E; Fraser, Graham M; Ellis, Christopher G

2018-05-25

Red blood cell oxygen saturation is an important indicator of oxygen supply to tissues in the body. Oxygen saturation can be measured by taking advantage of spectroscopic properties of hemoglobin. When this technique is applied to transmission microscopy, the calculation of saturation requires determination of incident light intensity at each pixel occupied by the red blood cell; this value is often approximated from a sequence of images as the maximum intensity over time. This method often fails when the red blood cells are moving too slowly, or if hematocrit is too large since there is not a large enough gap between the cells to accurately calculate the incident intensity value. A new method of approximating incident light intensity is proposed using digital inpainting. This novel approach estimates incident light intensity with an average percent error of approximately 3%, which exceeds the accuracy of the maximum intensity based method in most cases. The error in incident light intensity corresponds to a maximum error of approximately 2% saturation. Therefore, though this new method is computationally more demanding than the traditional technique, it can be used in cases where the maximum intensity-based method fails (e.g. stationary cells), or when higher accuracy is required. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

[Ischemic Changes in the Electrocardiogram and Circulatory Collapse Accompanied by Severe Anemia Owing to the Delay of Red Blood Cell Concentrate Transfusion in Two Patients with Intraoperative Massive Bleeding].

PubMed

Horiuchi, Toshinori; Noguchi, Teruo; Kurita, Naoko; Yamaguchi, Ayako; Takeda, Masafumi; Sha, Keiichi; Nagahata, Toshihiro

2016-01-01

We present two patients developing intraoperative massive bleeding and showed ischemic changes in the electrocardiogram and circulatory collapse accompanied by severe anemia owing to the delay of red blood cell concentrate transfusion. One patient underwent hepatectomy and the other pancreaticoduodenectomy. Their lowest hemoglobin concentration was around 2 g x dl(-1), and they showed ischemic changes in the electrocardiogram and severe decreases in blood pressure. The former received compatible red blood cell concentrate and the latter received uncrossmatched same blood group red blood cell concentrate immediately, and their electrocardiogram and blood pressure quickly improved. To avoid life-threatening anemia, emergency red blood cell concentrate transfusion including compatible different blood group transfusion should be applied for intraoperative massive bleeding.

[Can venous iron and tranexamic acid reduce the transfusion need? Report on a non randomized, case control study].

PubMed

Essola, L; Kouégnigan Rérambiah, L; Obame, R; Issembè, H; Sima Zué, A

2017-06-01

To evaluate if the association of injectable iron and tranexamic acid allows a significant saving in transfusion, in cases of myomectomies and hysterectomies. This is a prospective, non randomized study done over 8 months (from January 2013 to August 2013). Were included, patients undergoing hysterectomy or myomectomy who had a hemoglobin level greater than or equal to 8g/dl and less than 12g/dl. Two groups were compared: group A consisting of patients for whom a pack red cells was ordered and the group B which patients received intravenous iron preoperatively and tranexamic acid perioperatively. The level of hemoglobin, pre- and postoperative, the average number of blood units per patient and estimated blood loss was compared. The transfusion economy was evaluated. During this period, 87 patients with a mean age of 40±9 years (range: 23 and 70years) were included according to our criteria: 44 patients in group A and 43 patients in group B. Initial mean hemoglobin in both groups was 9.1±0.7g/dl. In group B, after iron administration, the mean hemoglobin was 11.3±0.7g/dl. The average number of red blood cells received intraoperative patient in group A was 1.54±0.51. The estimated blood loss was significant greater (P=0.0002) in group A (571.6±237.1ml) than in group B (213.7±131.7ml). No transfusion was performed in group B. The association intravenous iron and tranexamic acid resulted in the reduction of transfusion requirements in our setting. It could be integrated in the strategy for sparing blood transfusion in scheduled surgery with hemorrhagic risks. Copyright © 2017. Published by Elsevier SAS.

[Massive transfusion of washed red blood cells: acid-base and electrolyth changes for different wash solutions].

PubMed

Sümpelmann, R; Schürholz, T; Marx, G; Ahrenshop, O; Zander, R

2003-09-01

The composition of normal saline (NaCl), the standard wash solution for cell saver autotransfusion, is considerably different from physiologic plasma values in small infants. Therefore, we investigated acid-base and electrolyte changes during massive cell saver autotransfusion with different wash solutions in young pigs. After approval by the animal protection authorities 15 young pigs (weight 10.6 +/- 1.1 kg, blood volume 848 +/- 88 ml, mean+/-SD) underwent 15 cycles of cell saver autotransfusion (Haemolite 2plus, Haemonetics). For each cycle, 100 ml arterial blood was withdrawn, washed with NaCl, physiologic multielectrolyte solution (PME, V Infusionslösung 296 mval Elektrolyte, Baxter) or physiologic erythrocyte protection solution (PEP, 3.2 % gelatine, pH 7.40, cHCO3 24 mmol/l), and then retransfused. Analyses of acid-base, electrolyte, and hematologic parameters were performed for systemic and washed blood samples. For NaCl there was a progressive decrease in systemic pH, HCO3 and base excess (BE) and an increase in chloride values (Cl) (p < 0.05). Use of PME slightly decreased pH (n. s.), whereas HCO3, BE and Cl remained stable. PEP slightly increased pH, HCO3 and BE, and decreased Cl (n. s.). Free hemoglobin increased in NaCl and PME (p < 0.05) and was below baseline in PEP (n. s.). Lactic acid course was comparable in all groups. The use of NaCl as wash solution for massive autotransfusion resulted in metabolic acidosis caused by dilution of HCO3 and increased Cl values. Fewer systemic acid-base and electrolyte changes were observed, when blood was washed with PME or PEP. The decreased hemoglobin release with PEP is possibly due to a gelatine specific electrostatic surface coating of erythrocyte membranes. For massive transfusion of washed red blood cells, physiologic multielectrolyte solution and physiologic erythrocyte protection solution should be preferred to NaCl, especially for small infants.

Effects of lead shot ingestion on delta-aminolevulinic acid dehydratase activity, hemoglobin concentration, and serum chemistry in bald eagles

USGS Publications Warehouse

Hoffman, D.J.; Pattee, O.H.; Wiemeyer, Stanley N.; Mulhern, B.

1981-01-01

Lead shot ingestion by bald eagles (Haliaeetus leucocephalus) is considered to be widespread and has been implicated in the death of eagles in nature. It was recently demonstrated under experimental conditions that ingestion of as few as 10 lead shot resulted in death within 12 to 20 days. In the present study hematological responses to lead toxicity including red blood cell ALAD activity, hemoglobin concentration and 23 different blood serum chemistries were examined in five captive bald eagles that were unsuitable for rehabilitation and release. Eagles were dosed by force-feeding with 10 lead shot; they were redosed if regurgitation occurred. Red blood cell ALAD activity was inhibited by nearly 80% within 24 hours when mean blood lead concentration had increased to 0.8 parts per million (ppm). By the end of 1 week there was a significant decrease (20-25%) in hematocrit and hemoglobin, and the mean blood lead concentration was over 3 ppm. Within as little as 1-2 weeks after dosing, significant elevations in serum creatinine and serum alanine aminotransferase occurred, as well as a significant decrease in the ratio of serum aspartic aminotransferase to serum alanine aminotransferase. The mean blood lead concentration was over 5 ppm by the end of 2 weeks. These changes in serum chemistry may be indicative of kidney and liver alterations.

Non-invasive Self-Care Anemia Detection during Pregnancy Using a Smartphone Camera

NASA Astrophysics Data System (ADS)

Anggraeni, M. D.; Fatoni, A.

2017-02-01

Indonesian maternal mortality rate is the highest in South East Asia. Postpartum hemorrhage is the major causes of maternal mortality in Indonesia. Anemia during pregnancy contributes significantly to postpartum hemorrhage. Early detection of anemia during pregnancy may save mothers from maternal death. This research aim to develop a non-invasive self-care anemia detection based on the palpebral color observation and using a smartphone camera. The color intensity (Red, Green, and Blue) was then measured using a Colorgrab software (Loomatix) and analyzed compared to the hemoglobin concentration of the samples, measured using standard Spectrophotometer method. The result showed that the red color intensity had a high correlation (R2=0.814) with a linear regression of y=14.486x + 50.228. This preliminary study may be used as anemia early detection which more objective compared to visual assessment usually performed.

Sickling of red blood cells through rapid oxygen exchange in microfluidic drops.

PubMed

Abbyad, Paul; Tharaux, Pierre-Louis; Martin, Jean-Louis; Baroud, Charles N; Alexandrou, Antigoni

2010-10-07

We have developed a microfluidic approach to study the sickling of red blood cells associated with sickle cell anemia by rapidly varying the oxygen partial pressure within flowing microdroplets. By using the perfluorinated carrier oil as a sink or source of oxygen, the oxygen level within the water droplets quickly equilibrates through exchange with the surrounding oil. This provides control over the oxygen partial pressure within an aqueous drop ranging from 1 kPa to ambient partial pressure, i.e. 21 kPa. The dynamics of the oxygen exchange is characterized through fluorescence lifetime measurements of a ruthenium compound dissolved in the aqueous phase. The gas exchange is shown to occur primarily during and directly after droplet formation, in 0.1 to 0.5 s depending on the droplet diameter and speed. The controlled deoxygenation is used to trigger the polymerization of hemoglobin within sickle red blood cells, encapsulated in drops. This process is observed using polarization microscopy, which yields a robust criterion to detect polymerization based on transmitted light intensity through crossed polarizers.

Physiological red cell, 2,3-diphosphoglycerate increase by the sixth hour after birth.

PubMed

Barretto, O C; Nonoyama, K; Deutsch, A D; Ramos, J L

1995-01-01

As the available hemoglobin A1 at birth ranges from 20 to 30% a possible mechanism to favor oxygen release to the tissues could be a decrease of hemoglobin A1 affinity to oxygen. This may be accomplished by an increase in blood pH soon after birth and by an elevation in red cell 2,3-diphosphoglycerate (2,3-DPG). This hypothesis is supported by Valleri and Hirsch, who described a rapid 2,3-DPG recovery of transfused depleted 2,3-DPG red cells. That being so, we carried out this current study by assaying the 2,3-DPG of cord blood from 22 newborns and at 6, 24 and 72 hours after birth, as well as those enzymes assumed to be envolved in the 2,3-DPG levels regulation. 2,3-DPG (nmoles g-1 Hb) demonstrated the following values: cord blood: 9,770 +/- 1,026; 6h: 12,773 +/- 1,726; 72 h: 11,990 +/- 728, unveiling a distinct behavior of a sharp increase of 30% by the sixth hour. This confirmed our hypothesis. Regarding the metabolic mechanisms which can account for the 2,3-DPG increase, besides the rise of blood pH, we detected a significant decrease of the 2,3-DPG phosphatase activity, which might diminish the 2,3-DPG breakdown.

The prevalence of hemoglobin S and glucose-6-phosphate dehydrogenase deficiency in Jordanian newborn.

PubMed

Talafih, K; Hunaiti, A A; Gharaibeh, N; Gharaibeh, M; Jaradat, S

1996-10-01

The aim of this study was to determine the incidence of HbS and glucose-6-phosphate dehydrogenase (G6PD) deficiency in Jordanian newborn. A total of 181 male and female babies born at Princess Basma Teaching Hospital, randomly selected, and cord blood samples were collected, and the erythrocyte G6PD activity was measured, and the hemoglobin electrophoresis for blood lysate was conducted and scanned for HbS scanning. The frequencies of two major red cell genetic defects, sickle hemoglobin (HbS) and deficiency G6PD was determined, of the studied subjects 10 (11%) females and 11 (12%) males were found to be deficient in the G6PD gene. The frequency of HbS carriers among the females was 4% while it was 6% among males. The coincidence of both G6PD deficiency and sickle cell hemoglobin in the samples was 1%. No coincidence was found between G6PD deficiency and hyperbilirubinemia. A better understanding of the distributions of these genetic disorders has the potential to aid in the more efficient utilization of health care resources and improved planning.

Destruction of newly released red blood cells in space flight

NASA Technical Reports Server (NTRS)

Alfrey, C. P.; Udden, M. M.; Huntoon, C. L.; Driscoll, T.

1996-01-01

Space flight results in a rapid change in total blood volume, plasma volume, and red blood cell mass because the space to contain blood is decreased. The plasma volume and total blood volume decreases during the first hours in space and remain at a decreased level for the remainder of the flight. During the first several hours following return to earth, plasma volume and total blood volume increase to preflight levels. During the first few days in space recently produced red blood cells disappear from the blood resulting in a decrease in red blood cell mass of 10-15%. Red cells 12 d old or older survive normally and production of new cells continues at near preflight levels. After the first few days in space, the red cell mass is stable at the decreased level. Following return to earth the hemoglobin and red blood cell mass concentrations decrease reflecting the increase in plasma volume. The erythropoietin levels increase responding to "postflight anemia"; red cell production increases, and the red cell mass is restored to preflight levels after several weeks.

The influence of environmental P(O(2)) on hemoglobin oxygen saturation in developing zebrafish Danio rerio.

PubMed

Grillitsch, Sandra; Medgyesy, Nikolaus; Schwerte, Thorsten; Pelster, Bernd

2005-01-01

Several studies suggest that during early larval development of lower vertebrates convective blood flow is not essential to supply oxygen to the tissues, but information about the oxygenation status of larvae during the time of cutaneous respiration is still missing. If convective oxygen transport contributes to the oxygen supply to tissues, venous blood in the central circulatory system should be partly deoxygenated, and hyperoxia should increase the oxygen saturation of the hemoglobin. To analyze the changes in hemoglobin oxygen saturation induced by hyperoxic incubation, zebrafish larvae were incubated in a tiny chamber between polytetrafluoroethylene membranes (Teflon), so that the oxygen supply could be rapidly modified. Hemoglobin oxygen saturation was measured in vivo by combining video imaging techniques with a spectrophotometrical analysis of hemoglobin light absorption at specific wavelengths for maximal absorption of oxygenated and deoxygenated blood (413 nm and 431 nm, respectively) under normoxic conditions and after a 10 min period of hyperoxia (P(O(2))=100 kPa), assuming that at a P(O(2)) of 100 kPa the hemoglobin is fully saturated. The results demonstrated that red blood cell oxygenation of zebrafish larvae at 4 days post fertilization (d.p.f.), 5 d.p.f. and 12 d.p.f. could be increased by hyperoxia. The data suggest that at the time of yolk sac degradation (i.e. 4 d.p.f. and 5 d.p.f.), when the total surface area of the animal is reduced, bulk diffusion of oxygen may not be sufficient to prevent a partial deoxygenation of the hemoglobin. The decrease in hemoglobin oxygenation observed at 12 d.p.f. confirms earlier studies indicating that at 12-14 d.p.f., convective oxygen transport becomes necessary to ensure oxygen supply to the growing tissues.

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

The Relationship Between Preoperative Hemoglobin Concentration, Use of Hospital Resources, and Outcomes in Cardiac Surgery.

PubMed

Hallward, George; Balani, Nikhail; McCorkell, Stuart; Roxburgh, James; Cornelius, Victoria

2016-08-01

Preoperative anemia is an established risk factor associated with adverse perioperative outcomes after cardiac surgery. However, limited information exists regarding the relationship between preoperative hemoglobin concentration and outcomes. The aim of this study was to investigate how outcomes are affected by preoperative hemoglobin concentration in a cohort of patients undergoing cardiac surgery. A retrospective, observational cohort study. A single-center tertiary referral hospital. The study comprised 1,972 adult patients undergoing elective and nonelective cardiac surgery. The independent relationship of preoperative hemoglobin concentration was explored on blood transfusion rates, return to the operating room for bleeding and/or cardiac tamponade, postoperative intensive care unit (ICU) and in-hospital length of stay, and mortality. The overall prevalence of anemia was 32% (629/1,972 patients). For every 1-unit increase in hemoglobin (g/dL), blood transfusion requirements were reduced by 11%, 8%, and 3% for red blood cell units, platelet pools, and fresh frozen plasma units, respectively (adjusted incident rate ratio 0.89 [95% CI 0.87-0.91], 0.92 [0.88-0.97], and 0.97 [0.96-0.99]). For each 1-unit increase in hemoglobin (g/dL), the probability (over time) of discharge from the ICU and hospital increased (adjusted hazard ratio estimates 1.04 [1.00-1.08] and 1.12 [1.12-1.16], respectively). A lower preoperative hemoglobin concentration resulted in increased use of hospital resources after cardiac surgery. Each g/dL unit fall in preoperative hemoglobin concentration resulted in increased blood transfusion requirements and increased postoperative ICU and hospital length of stay. Copyright © 2016 Elsevier Inc. All rights reserved.

Novel noninvasive point-of-care device for real time hemoglobin monitoring

NASA Astrophysics Data System (ADS)

Timm, Ulrich; Gewiss, Helge; Kraitl, Jens; Stuepmann, Kirstin; Hinz, Michael; Koball, Sebastian; Ewald, Hartmut

2014-02-01

During the perioperative period, which includes the period before surgery and after surgery (postoperative), it is essential to measure diagnostic parameters such as: blood oxygen saturation; hemoglobin (Hb) concentration; and pulse rate. The Hb concentration in human blood is an important parameter to evaluate the physiological condition of an individual, as Hb is the oxygen carrying component of red blood cells. By determining the Hb concentration, it is possible, for example, to observe intraoperative or postoperative bleeding, and use this information as a trigger for autologous/ allogenic blood transfusions. In blood donation center it is also an essential parameter for the decision regarding the acceptance of the donor.

Mössbauer studies of hemoglobin in erythrocytes exposed to neutron radiation

NASA Astrophysics Data System (ADS)

Niemiec, Katarzyna; Kaczmarska, Magdalena; Buczkowski, Mateusz; Fornal, Maria; Pohorecki, Władysław; Matlak, Krzysztof; Korecki, Józef; Grodzicki, Tomasz; Burda, Kvetoslava

2012-03-01

We studied radiation effects on the stability of various states of hemoglobin (Hb) in red blood cells (RBC) irradiated with a very low dose of neutron rays, 50 μGy. We investigated RBCs isolated from blood of healthy donors. Mössbauer spectroscopy was applied to monitor different forms of Hb. Our results show, for the first time, that oxyhemoglobin (OxyHb) and deoxyhemoglobin (DeoxyHb) are two Hb forms sensitive to such a low neutron radiation. Both Hbs change into a new Hb form (Hbirr). Additionally, OxyHb transfers into HbOH/H2O, which under our experimental conditions is resistant to the action of neutron rays.

Mössbauer studies of hemoglobin in high altitude polycythemia

NASA Astrophysics Data System (ADS)

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

1990-07-01

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

21 CFR 862.1785 - Urinary urobilinogen (nonquantitative) test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Urinary urobilinogen (nonquantitative) test system. 862.1785 Section 862.1785 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... urobilinogen (a bile pigment degradation product of red cell hemoglobin) in urine. Estimations obtained by this...

Transcutaneous regional venous oximetry: a feasibility study.

PubMed

Thiele, Robert H; Tucker-Schwartz, Jason M; Lu, Yao; Gillies, George T; Durieux, Marcel E

2011-06-01

The arterial pulse oximeter, which was introduced clinically in the 1970s, is a convenient, useful, and now ubiquitous anesthesia monitor. Unfortunately, although percent saturation of arterial hemoglobin is, along with cardiac output and concentration of hemoglobin, one of 3 components of oxygen delivery, it does not indicate whether oxygen delivery to a region of interest is adequate. Knowledge of peripheral or regional venous oxygen saturation (Sxvo₂) may lend insight into analysis of regional oxygen supply and demand. Our goal was to assess the suitability of 3 anatomic sites for the transcutaneous assessment of Sxvo₂. Using a Nonin reflectance oximetry probe (provided by Nonin Medical, Plymouth, MN) placed directly over the antecubital, external jugular, and internal jugular veins in 10 volunteers, we measured the absorbance of red and infrared electromagnetic radiation. We performed fast Fourier transformation on these absorbance waveforms. The ratio of pulsatile absorbance of red and infrared radiation at different frequencies was compared with nonpulsatile absorption, and Sxvo₂ was calculated based on previously derived empiric correlations. Estimates of transcutaneous Sxvo₂ ranged from 41% to 97%, with mean values of 75%, 80%, and 80% at the antecubital, external jugular, and internal jugular veins, respectively. Overall, 93% of predicted Sxvo₂ values were < 90%. Validation and subsequent improvement of this technique requires correlation of our results with venous blood gas measurements, followed by incorporation of technologies from related fields in oximetry (fetal reflectance oximetry and near-infrared spectroscopy), as well as the development of advanced signal processing techniques.

Perioperative hemoglobin area under the curve is an independent predictor of renal failure after cardiac surgery. Results from a Spanish multicenter retrospective cohort study

PubMed Central

Duque-Sosa, Paula; Iribarren, María Josefa; Rábago, Gregorio

2017-01-01

Perioperative anemia is an important risk factor for cardiac surgery-associated acute kidney injury (CSA-AKI). Nonetheless, the severity of the anemia and the time in the perioperative period in which the hemoglobin level should be considered as a risk factor is conflicting. The present study introduces the concept of perioperative hemoglobin area under the curve (pHb-AUC) as a surrogate marker of the evolution of perioperative hemoglobin concentration. Through a retrospective analysis of prospectively collected data, we assessed this new variable as a risk factor for the development of acute kidney injury after cardiac surgery in 966 adult patients who underwent cardiac surgery with cardiopulmonary bypass, at twenty-three academic hospitals in Spain. Exclusion criteria were patients on renal replacement therapy, who needed a reoperation because of bleeding and/or with missing perioperative hemoglobin or creatinine values. Using a multivariate regression analysis, we found that a pHb-AUC <19 g/dL was an independent risk factor for CSA-AKI even after adjustment for intraoperative red blood cell transfusion (OR 1.41, p <0.05). It was also associated with mortality (OR 2.48, p <0.01) and prolonged hospital length of stay (4.67 ± 0.99 days, p <0.001) PMID:28225801

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.

Mobile phone exposure influences some erythrocytes parameters in vitro. A novel source of preanalytical variability?

PubMed

Danese, Elisa; Lippi, Giuseppe; Brocco, Giorgio; Montagnana, Martina; Salvagno, Gian Luca

2016-06-01

The effect of radiofrequency exposure on human health and health care equipment is a matter of ongoing debate. This study was planned to investigate the influence of radiofrequency (RF) waves emitted by a commercial mobile phone on red blood cells (RBC) in vitro. The study population consisted of 16 ostensibly healthy volunteers. Two whole blood specimens were collected from each volunteer. One sample was placed in a plastic rack, 1 cm distant from the chassis of a commercial mobile phone which was activated by a remote phone call lasting 30 min. The other blood sample was placed in another plastic rack, but was kept distant from any type of RF source. The main RBC parameters including RBC count, hematocrit (Ht), hemoglobin, mean corpuscular platelet volume (MPV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC) and RBC distribution width (RDW-CV) were assessed with an Advia 2120. The exposure of whole blood to the mobile phone call significantly increased Ht, hemoglobin, MCV and MCH, whereas the RBC count, MCHC and RDW-CV remained unchanged. A significant correlation was observed between variation of Ht and those of hemoglobin (p=0.008), MCV (p=0.009) or MCH (p=0.037), as well as between hemoglobin and MCV (p=0.048). Increased values were found in 13/16 (81%) samples for both Ht and hemoglobin, 14/16 (88%) samples for MCH and 16/16 (100%) samples for MCV. These results suggest that close mobile phone exposure may be an unappreciated and possibly underestimated cause of preanalytical bias in RBC testing.

Studies on the erythron and the ferrokinetic responses in beagles adapted to hypergravity

NASA Technical Reports Server (NTRS)

Beckman, D. A.; Evans, J. W.; Oyama, J.

1978-01-01

Red cell survival, ferrokinetics, and hematologic parameters were investigated in beagle dogs exposed to chronic hypergravity (2.6 Gx). Ineffective erythropoiesis, red cell mass, plasma volume, and Cr-51-elution were significantly increased; maximum Fe-59 incorporation was decreased; and there was no change in the mean erythrocyte life span following autologous injection of Cr-51-labeled red cells and Fe-59-labeled transferrin. Red cell count, F(cells), total body hemoglobin (Hb), susceptability to osmotic lysis, and differential reticulocyte count were increased. White blood cell count, venous blood %Hb, mean cell volume, mean cell Hb, mean cell Hb concentration, and serum iron were decreased. No changes were observed for body mass, mg Fe per g Hb, iron binding capacity, percent saturation of iron carrying capacity, or the electrophoretic mobility of purified Hb. This study indicated that chronic exposure to hypergravity induced changes in red cell size, volume, total mass, and membrane permeability.

Development of Recombinant Hemoglobin-Based Oxygen Carriers

PubMed Central

Varnado, Cornelius L.; Mollan, Todd L.; Birukou, Ivan; Smith, Bryan J.Z.; Henderson, Douglas P.

2013-01-01

Abstract Significance: The worldwide blood shortage has generated a significant demand for alternatives to whole blood and packed red blood cells for use in transfusion therapy. One such alternative involves the use of acellular recombinant hemoglobin (Hb) as an oxygen carrier. Recent Advances: Large amounts of recombinant human Hb can be expressed and purified from transgenic Escherichia coli. The physiological suitability of this material can be enhanced using protein-engineering strategies to address specific efficacy and toxicity issues. Mutagenesis of Hb can (i) adjust dioxygen affinity over a 100-fold range, (ii) reduce nitric oxide (NO) scavenging over 30-fold without compromising dioxygen binding, (iii) slow the rate of autooxidation, (iv) slow the rate of hemin loss, (v) impede subunit dissociation, and (vi) diminish irreversible subunit denaturation. Recombinant Hb production is potentially unlimited and readily subjected to current good manufacturing practices, but may be restricted by cost. Acellular Hb-based O2 carriers have superior shelf-life compared to red blood cells, are universally compatible, and provide an alternative for patients for whom no other alternative blood products are available or acceptable. Critical Issues: Remaining objectives include increasing Hb stability, mitigating iron-catalyzed and iron-centered oxidative reactivity, lowering the rate of hemin loss, and lowering the costs of expression and purification. Although many mutations and chemical modifications have been proposed to address these issues, the precise ensemble of mutations has not yet been identified. Future Directions: Future studies are aimed at selecting various combinations of mutations that can reduce NO scavenging, autooxidation, oxidative degradation, and denaturation without compromising O2 delivery, and then investigating their suitability and safety in vivo. Antioxid. Redox Signal. 18, 2314–2328. PMID:23025383

Multimodal optical imaging of microvessel network convective oxygen transport dynamics.

PubMed

Dedeugd, Casey; Wankhede, Mamta; Sorg, Brian S

2009-04-01

Convective oxygen transport by microvessels depends on several parameters, including red blood cell flux and oxygen saturation. We demonstrate the use of intravital microscopy techniques to measure hemoglobin saturations, red blood cell fluxes and velocities, and microvessel cross-sectional areas in regions of microvascular networks containing multiple vessels. With these methods, data can be obtained at high spatial and temporal resolution and correlations between oxygen transport and hemodynamic parameters can be assessed. In vivo data are presented for a mouse mammary adenocarcinoma grown in a dorsal skinfold window chamber model.

Effect of Red Blood Cell Storage on Cardiac Performance. Improved Myocardial Oxygen Delivery and Function during Constant Flow Coronary Perfusion with Low Oxy-Hemoglobin Affinity Human Red Blood Cells in Normothermic and Hypothermic Rabbit Hearts.

DTIC Science & Technology

1983-02-01

with an isovolumic left ven- tricular balloon. Coronary flow was held constant to simulate the physiolog of coronary atherosclerosis and other...erythrocyte DPG content can potentially benefit patients with coronary atherosclerosis , or other states with a limited coronary vasodilator reserve, who...Coronary flow was held constant to simulate the physiology of coronary atherosclerosis and other conditions of limited coronary vasodilator reserve

Hematology and immunology studies

NASA Technical Reports Server (NTRS)

Kimzey, S. L.

1977-01-01

A coordinated series of experiments were conducted to evaluate immunologic and hemotologic system responses of Skylab crewmen to prolonged space flights. A reduced PHA responsiveness was observed on recovery, together with a reduced number of T-cells, with both values returning to normal 3 to 5 days postflight. Subnormal red cell count, hemoglobin concentration, and hematocrit values also returned gradually to preflight limits. Most pronounced changes were found in the shape of red blood cells during extended space missions with a rapid reversal of these changes upon reentry into a normal gravitational environment.

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.

A Red Carpet for Iron Metabolism

PubMed Central

Muckenthaler, Martina U.; Rivella, Stefano; Hentze, Matthias W.; Galy, Bruno

2017-01-01

200 billion red blood cells (RBCs) are produced every day, requiring more than 2 × 3 1015 iron atoms every second to maintain adequate erythropoiesis. These numbers translate into 20 mL of blood being produced each day, containing 6 g of hemoglobin and 20 mg of iron. These impressive numbers illustrate why the making and breaking of RBCs is at the heart of iron physiology, providing an ideal context to discuss recent progress in understanding the systemic and cellular mechanisms that underlie the regulation of iron homeostasis and its disorders. PMID:28129536

Red blood cells, still vital after all these years: Commentary on Canadian Blood Services' International Symposium 2017.

PubMed

Qadri, Syed M; Donkor, David A; Yan, Matthew; Ning, Shuoyan; Branch, Donald R; Seghatchian, Jerard; Sheffield, William P

2018-04-01

Canadian Blood Services (CBS), Canada's national blood transfusion service, has for many years sponsored an annual conference, for the education and awareness of interested participants, showcasing the latest evidence-based understanding of both basic science and clinical issues in transfusion medicine and science. The 15th iteration of this symposium took place September 9, 2017 and focused on some of the vital aspects of red blood cells (RBC), in line with the" 3Rs" concept, namely the provision of the Right red blood cell (RBC) product to the Right patient at the Right time. Presentations touched upon: the evolution of blood banking in North America; the monocyte monolayer assay as a predictor of post-transfusion hemolysis; hemoglobin-based oxygen carriers; RBC alloimmunization; serological approaches to complex RBC antibody problems; randomized clinical trials related to the age of stored RBC; RBC genotyping; pathophysiology, prevention and treatment of hemolytic disease of the fetus and newborn (HDFN); and testing and timing in perinatal serology. This commentary provides summaries of all speakers' presentations annotated with relevant references. Special thanks are due to all contributors for their praiseworthy approaches in sharing their experiences and knowledge on this interesting scientific/clinical and management theme. Copyright © 2018 Elsevier Ltd. All rights reserved.

Numerical simulation of oxygen delivery to muscle tissue in the presence of hemoglobin-based oxygen carriers.

PubMed

Patton, Jaqunda N; Palmer, Andre F

2006-01-01

This work represents a culmination of research on oxygen transport to muscle tissue, which takes into account oxygen transport due to convection, diffusion, and the kinetics of simultaneous reactions between oxygen and hemoglobin and myoglobin. The effect of adding hemoglobin-based oxygen carriers (HBOCs) to the plasma layer of blood in a single capillary surrounded by muscle tissue based on the geometry of the Krogh tissue cylinder is examined for a range of HBOC oxygen affinity, HBOC concentration, capillary inlet oxygen tension (pO(2)), and hematocrit. The full capillary length of the hamster retractor muscle was modeled under resting (V(max) = 1.57 x 10(-4) mLO(2) mL(-1) s(-1), cell velocity (v(c)) = 0.015 cm/s) and working (V(max) = 1.57 x 10(-3) mLO(2) mL(-1) s(-1), v(c) = 0.075 cm/s) conditions. Two spacings between the red blood cell (RBC) and the capillary wall were examined, corresponding to a capillary with and without an endothelial surface layer. Simulations led to the following conclusions, which lend physiological insight into oxygen transport to muscle tissue in the presence of HBOCs: (1) The reaction kinetics between oxygen and myoglobin in the tissue region, oxygen and HBOCs in the plasma, and oxygen and RBCs in the capillary lumen should not be neglected. (2) Simulation results yielded new insight into possible mechanisms of oxygen transport in the presence of HBOCs. (3) HBOCs may act as a source or sink for oxygen in the capillary and may compete with RBCs for oxygen. (4) HBOCs return oxygen delivery to muscle tissue to normal for varying degrees of hypoxia (inlet capillary pO(2) < 30 mmHg) and anemia (hematocrit < 46%) for the hamster model.

Increased viscosity of hemoglobin-based oxygen carriers retards NO-binding when perfused through narrow gas-permeable tubes.

PubMed

Sakai, Hiromi; Okuda, Naoto; Takeoka, Shinji; Tsuchida, Eishun

2011-03-01

Increased fluid viscosity of a solution of hemoglobin-based oxygen carriers (HBOCs) reduces vasoconstrictive effects because increased shear stress on the vascular wall enhances the production of vasorelaxation factors such as NO. Nevertheless, on a microcirculatory level, it remains unclear how viscosity affects the reaction of HBOCs and NO. In this study, different HBOCs were perfused through narrow gas-permeable tubes (25 μm inner diameter at 1 mm/s centerline velocity; hemoglobin concentration [Hb]=5 g/dL). The reaction was examined microscopically based on the Hb visible-light absorption spectrum. When immersed in a NO atmosphere, the NO-binding of deoxygenated Hb solution (viscosity, 1.1 cP at 1000 s(-1)) in the tube occurred about twice as rapidly as that of red blood cells (RBCs): 1.6 cP. Binding was reduced by PEGylation (PEG-Hb, 7.7 cP), by addition of a high molecular weight hydroxyethyl starch (HES) (2.8 cP), and by encapsulation to form Hb-vesicles (HbVs, 1.5 cP; particle size 279 nm). However, the reduction was not as great as that shown for RBCs. A mixture of HbVs and HES (6.2 cP) showed almost identical NO-binding to that of RBCs. Higher viscosity and particle size might reduce lateral diffusion when particles are flowing. The HbVs with HES showed the slowest NO-binding. Furthermore, Hb encapsulation and PEGylation, but not HES-addition, tended to retard CO-binding. Increased viscosity reportedly enhances production of endothelium NO. In addition, our results show that the increased viscosity also inhibits the reaction with NO. Each effect might mitigate vasoconstriction. Copyright © 2010 Elsevier Inc. All rights reserved.

Thermodynamic approach to oxygen delivery in vivo by natural and artificial oxygen carriers.

PubMed

Bucci, Enrico

2009-06-01

Oxygen is a toxic gas, still indispensable to aerobic life. This paper explores how normal physiology uses the physico-chemical and thermodynamic characteristics of oxygen for transforming a toxic gas into a non toxic indispensable metabolite. Plasma oxygen concentration is in the range of 10(-5) M, insufficient to sustain metabolism. Oxygen carriers, present in blood, release oxygen into plasma, thereby replacing consumed oxygen and buffering PO(2) near their P(50). They are the natural cell-bound carriers, like hemoglobin inside red cells, myoglobin inside myocytes, and artificial cell-free hemoglobin-based oxygen carriers (HBOC) dissolved in plasma. Metabolic oxygen replacement can be defined as cell-bound and cell-free delivery. Cell-bound delivery is retarded by the slow diffusion of oxygen in plasma and interstitial fluids. The 40% hematocrit of normal blood compensates for the delay, coping with the fast oxygen consumption by mitochondria. Facilitated oxygen diffusion by HBOCs corrects for the slow diffusion, making cell-free delivery relatively independent from P(50). At all oxygen affinities, HBOCs produce hyperoxygenations that are compensated by vasoconstrictions. There is a strict direct correlation between the rate of oxygen replacement and hemoglobin content of blood. The free energy loss of the gradient adds a relevant regulation of tissues oxygenation. Oxygen is retained intravascularly by the limited permeability to gases of vessel walls.

Medical Surveillance Monthly Report. Volume 19, Number 7

DTIC Science & Technology

2012-07-01

education for recruits at acces- sion. While the Marine Corps and...other Services. This may reflect that most servicewomen receive chlamydia screening, treatment and education imme- diately upon accession, while... hemoglobin , the substance in red blood cells (RBCs) that carries oxygen from the lungs to the rest of the body. In the face of

Adenosine triphosphate and diphosphoglycerate levels in red blood cells from patients with Down's syndrome.

PubMed

Knull, H R; Bronstein, W W; Porter, P J

1978-09-15

The levels of ATP and ATP plus DPG were significantly elevated in erythrocytes from Down's syndrome patients when compared to erythrocytes from age matched controls. The hemoglobin content and hematocrit values were significantly reduced. The resultant tendency towards anemia probably explains the elevation in metabolite levels.

Simultaneous determination of hemolysis and hematocrit in extracorporeal circulation by plasma surface reflectance spectroscopy.

PubMed

Sakota, Daisuke; Kani, Yuki; Kosaka, Ryo; Nishida, Masahiro; Maruyama, Osamu

2013-01-01

To achieve quantitative non-invasive optical diagnosis of blood abnormalities during extracorporeal circulation therapies, plasma surface reflectance spectroscopy was developed by implementing oblique-incidence optical fiber reflectometry on the surface of circulating blood. The reflected light in the wavelength range from 450 to 600 nm changed with respect to the plasma free hemoglobin level and could be used to quantify the free hemoglobin at an accuracy of 5.7 ± 3.5 mg/dL. In contrast, the spectrum did not changed by varying the hematocrit. In the wavelength range from 600 to 800 nm, the obtained spectrum was affected by both the hematocrit change and hemolysis. The linear correlation between the hematocrit value and the spectrum was confirmed at R(2) = 0.99. The feasibility of determining of the hematocrit of arbitrary hemolyzed blood was confirmed. The developed system permits the extraction of the optical characteristics of both plasma and red blood cells without centrifugation. The study establishes non-invasive optical diagnostics capable of analyzing the optical properties of both plasma and red blood cells.

Mantle Cell Hyperplasia of Peripheral Lymph Nodes as Initial Manifestation of Sickle Cell Disease.

PubMed

Monabbati, Ahmad; Noori, Sadat; Safaei, Akbar; Ramzi, Mani; Eghbali, Seyedsajjad; Adib, Ali

2016-01-01

Sickle cell disease (SCD) is a well known hemoglobinopathy with usual manifestations including anemia, hyperbilirubinemia, and vasoocclusive complications. Despite presence of mild splenomegaly in early phase of the disease, lymphadenopathy is not an often finding of SCD. We introduce an undiagnosed case of SCD who presented in third decade of his life with multiple cervical lymphadenopathies and mild splenomegaly persistent for about five years. Histopathologic examination of the resected lymph nodes showed expansion of the mantle cell layers of secondary follicles as well as several monomorphic mantle cell nodules. To rule out possibility of a malignant process involving lymph nodes, an immunohistochemical panel was ordered which was in favor of benign mantle cell hyperplasia. Immunoglobulin gene rearrangement study showed no clonal bands and confirmed benign nature of the process. Respecting mild abnormalities on Complete Blood Count, peripheral blood smear was reviewed revealing some typical sickle red blood cells as well as rare nucleated red blood cells. Solubility test for hemoglobin (HB) S was positive. Hemoglobin electrophoresis confirmed diagnosis of homozygous HbS disease.

[Full blood count reference values in children of 8 to 12 years old residing at 2,760 m above sea level].

PubMed

Armando García-Miranda, L; Contreras, I; Estrada, J A

2014-04-01

To determine reference values for full blood count parameters in a population of children 8 to 12 years old, living at an altitude of 2760 m above sea level. Our sample consisted of 102 individuals on whom a full blood count was performed. The parameters included: total number of red blood cells, platelets, white cells, and a differential count (millions/μl and %) of neutrophils, lymphocytes, monocytes, eosinophils and basophils. Additionally, we obtained values for hemoglobin, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin, concentration of corpuscular hemoglobin and red blood cell distribution width. The results were statistically analyzed with a non-parametric test, to divide the sample in quartiles and obtain the lower and upper limits for our intervals. Moreover, the values for the intervals obtained from this analysis were compared to intervals obtained estimating+- 2 standard deviations above and below from our mean values. Our results showed significant differences compared to normal interval values reported for the adult Mexican population in most of the parameters studied. The full blood count is an important laboratory test used routinely for the initial assessment of a patient. Values of full blood counts in healthy individuals vary according to gender, age and geographic location; therefore, each population should have its own reference values. Copyright © 2013 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

Hematologic and Biochemical Values of Wild Red-Tailed Amazon Parrot (Amazona brasiliensis) Nestlings With Abnormal Clinical Examination in Rasa Island, Brazil.

PubMed

Vaz, Frederico Fontanelli; Locatelli-Dittrich, Rosangela; Beltrame, Olair Carlos; Sipinski, Elenise Angelotti Bastos; Abbud, Maria Cecília; Sezerban, Rafael Meirelles

2016-12-01

The red-tailed Amazon parrot (Amazona brasiliensis) is an endangered psittacine species, but little information is available about abnormal clinical findings and hematologic and biochemical values of this species, which are important for monitoring the health of this population. To determine hematologic and biochemical values for wild red-tailed parrot nestlings exhibiting abnormal clinical findings, 31 nestlings from the Rasa Island (Paraná State, Southern Brazil) were physically restrained for clinical examination and blood sample collection. On physical examination, 26 birds had mild abnormalities and 5 had severe disorders. Parrots were divided into 5 groups according to the following clinical findings: presence of ectoparasites (group 1), respiratory disorders (group 2), chronic skin lesions caused by fly larvae (group 3), beak disorders (group 4), and severe clinical signs (group 5). Abnormal hematologic and biochemical findings in the nestlings were high total protein in group 3; low values for hemoglobin and mean corpuscular hemoglobin concentration in group 4; low glucose concentration, high mean absolute heterophil count, and high heterophil : lymphocyte ratio in group 5; high concentrations of total plasma protein in groups 3 and 4; and high globulin concentration in groups 3 and 5. In general, the population assessed was in good condition. These results provide a guide to the expected clinical findings associated with hematologic and biochemical concentrations in a population of free-living parrots with abnormal clinical examination findings. The data support the conservation planning and health monitoring of the endangered red-tailed Amazon parrot.

Image analysis of skin color heterogeneity focusing on skin chromophores and the age-related changes in facial skin.

PubMed

Kikuchi, Kumiko; Masuda, Yuji; Yamashita, Toyonobu; Kawai, Eriko; Hirao, Tetsuji

2015-05-01

Heterogeneity with respect to skin color tone is one of the key factors in visual perception of facial attractiveness and age. However, there have been few studies on quantitative analyses of the color heterogeneity of facial skin. The purpose of this study was to develop image evaluation methods for skin color heterogeneity focusing on skin chromophores and then characterize ethnic differences and age-related changes. A facial imaging system equipped with an illumination unit and a high-resolution digital camera was used to develop image evaluation methods for skin color heterogeneity. First, melanin and/or hemoglobin images were obtained using pigment-specific image-processing techniques, which involved conversion from Commission Internationale de l'Eclairage XYZ color values to melanin and/or hemoglobin indexes as measures of their contents. Second, a spatial frequency analysis with threshold settings was applied to the individual images. Cheek skin images of 194 healthy Asian and Caucasian female subjects were acquired using the imaging system. Applying this methodology, the skin color heterogeneity of Asian and Caucasian faces was characterized. The proposed pigment-specific image-processing techniques allowed visual discrimination of skin redness from skin pigmentation. In the heterogeneity analyses of cheek skin color, age-related changes in melanin were clearly detected in Asian and Caucasian skin. Furthermore, it was found that the heterogeneity indexes of hemoglobin were significantly higher in Caucasian skin than in Asian skin. We have developed evaluation methods for skin color heterogeneity by image analyses based on the major chromophores, melanin and hemoglobin, with special reference to their size. This methodology focusing on skin color heterogeneity should be useful for better understanding of aging and ethnic differences. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Intrinsic toxicity of hemoglobin: how to counteract it.

PubMed

Simoni, Jan; Simoni, Grace; Moeller, John F

2009-02-01

The development of safe and effective blood substitutes is of great importance in both civilian and military medicine. The currently tested hemoglobin (Hb)-based oxygen carriers, however, have toxicity and efficacy problems. A number of unwanted effects have been observed in human trials, creating doubts about their clinical usefulness. In some subjects, vasoconstriction and decreased blood flow to the vital organs, heart attack, stroke, systemic inflammation, organ damage, and even death, have been attributed to the transfusion of these experimental products. Hb is a well-known pressor agent and strong oxidant, although the full understanding of its intrinsic toxicity is yet to be uncovered. In particular, the complete mechanism of Hb-induced vasoconstriction needs full elucidation. Knowledge of the biological events that trigger the induction of genes upon treatment with redox-active Hb, as well as its catabolism, is still incomplete. It seems that our limited knowledge of free Hb effects in vivo is the main reason for not yet having a viable substitute of human blood. The future for universal red cell substitutes is in the new-generation products that address all of Hb's intrinsic toxicity issues.

Nitric oxide pathology and therapeutics in sickle cell disease.

PubMed

Kim-Shapiro, Daniel B; Gladwin, Mark T

2018-01-01

Sickle cell disease is caused by a mutant form of hemoglobin that polymerizes under hypoxic conditions which leads to red blood cell (RBC) distortion, calcium-influx mediated RBC dehydration, increased RBC adhesivity, reduced RBC deformability, increased RBC fragility, and hemolysis. These impairments in RBC structure and function result in multifaceted downstream pathology including inflammation, endothelial cell activation, platelet and leukocyte activation and adhesion, and thrombosis, all of which contribute vascular occlusion and substantial morbidity and mortality. Hemoglobin released upon RBC hemolysis scavenges nitric oxide (NO) and generates reactive oxygen species (ROS) and thereby decreases bioavailability of this important signaling molecule. As the endothelium-derived relaxing factor, NO acts as a vasodilator and also decreases platelet, leukocyte, and endothelial cell activation. Thus, low NO bioavailability contributes to pathology in sickle cell disease and its restoration could serve as an effective treatment. Despite its promise, clinical trials based on restoring NO bioavailability have so far been mainly disappointing. However, particular "NO donating" agents such as nitrite, which unlike some other NO donors can improve sickle RBC properties, may yet prove effective.

Transfusion strategy for acute upper gastrointestinal bleeding.

PubMed

Handel, James; Lang, Eddy

2015-09-01

Clinical question Does a hemoglobin transfusion threshold of 70 g/L yield better patient outcomes than a threshold of 90 g/L in patients with acute upper gastrointestinal bleeding? Article chosen Villanueva C, Colomo A, Bosch A, et al. Transfusion strategies for acute upper gastrointestinal bleeding. N Engl J Med 2013;368(1):11-21. Study objectives The authors of this study measured mortality, from any cause, within the first 45 days, in patients with acute upper gastrointestinal bleeding, who were managed with a hemoglobin threshold for red cell transfusion of either 70 g/L or 90 g/L. The secondary outcome measures included rate of further bleeding and rate of adverse events.

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.

Membrane-bound 2,3-diphosphoglycerate phosphatase of human erythrocytes.

PubMed

Schröter, W; Neuvians, M

1970-12-01

Gradual osmotic hemolysis of human erythrocytes reduces the cell content of whole protein, hemoglobin, 2,3-diphosphoglycerate and triosephosphate isomerase extensively, but not that of membrane protein and 2,3-diphosphoglycerate phosphatase. After the refilling of the ghosts with 2,3-diphosphoglycerate and reconstitution of the membrane, the 2,3-diphosphoglycerate phosphatase activity equals that of intact red cells. The membrane-bound 2,3-diphosphoglycerate phosphatase can be activated by sodium hyposulfite. The enzyme system of ghosts seems to differ from that of intact red cells with regard to the optima of pH and temperature. It remains to be elucidated if the membrane binding of the 2,3-diphosphoglycerate phosphatase is related to the transfer of inorganic phosphate across the red cell membrane.

Characterization of morphological response of red cells in a sucrose solution.

PubMed

Rudenko, Sergey V

2009-01-01

The dynamics of red cell shape changes following transfer into sucrose media having a low chloride content was studied. Based on a large number of measurements, six types of morphological response (MR), differing both in the degree of shape changes and the time course of the process, were identified. The most prominent type of response is a triphasic sequence of shape changes consisting of a fast transformation into a sphere (phase 1), followed by restoration of the discoid shape (phase 2) and final transformation into spherostomatocytes (phase 3), with individual parameters which could vary significantly. It was found that individual morphological response exhibited day to day variations, depending on the initial state of the red blood cells and the donor, but to a larger extent depended on the composition of the sucrose solution, such as concentration and type of buffers, the presence of EDTA, calcium, as well as very small amounts of extracellular hemoglobin. MR shows strong pH and ionic strength dependence. Low pH inhibited phase 1 and high pH changed dramatically the time course of the response. Increasing ionic strength inhibited all phases of MR, and at concentrations above 10-20 mM NaCl it was fully suppressed. Tris and phosphate were also inhibitory whereas HEPES, MOPS and Tricine were less effective. MR occurred also in hypertonic or hypotonic sucrose solutions, with exception of extreme hypotonicity due to volume restrictions. It is concluded that strong membrane depolarization per se is not a causal factor leading to MR, and its different phases could be regulated independently. For some types of morphological response the fast shape transformation from sphere to disc and back to sphere occurs within a 10 s time interval and could be accelerated several fold in the presence of a small amount of hemoglobin. It is suggested that MR represents a type of general cell reaction that occurs upon exposure to low ionic strength.

Globin switches in yolk sac-like primitive and fetal-like definitive red blood cells produced from human embryonic stem cells.

PubMed

Qiu, Caihong; Olivier, Emmanuel N; Velho, Michelle; Bouhassira, Eric E

2008-02-15

We have previously shown that coculture of human embryonic stem cells (hESCs) for 14 days with immortalized fetal hepatocytes yields CD34(+) cells that can be expanded in serum-free liquid culture into large numbers of megaloblastic nucleated erythroblasts resembling yolk sac-derived cells. We show here that these primitive erythroblasts undergo a switch in hemoglobin (Hb) composition during late terminal erythroid maturation with the basophilic erythroblasts expressing predominantly Hb Gower I (zeta(2)epsilon(2)) and the orthochromatic erythroblasts hemoglobin Gower II (alpha(2)epsilon(2)). This suggests that the switch from Hb Gower I to Hb Gower II, the first hemoglobin switch in humans is a maturation switch not a lineage switch. We also show that extending the coculture of the hESCs with immortalized fetal hepatocytes to 35 days yields CD34(+) cells that differentiate into more developmentally mature, fetal liver-like erythroblasts, that are smaller, express mostly fetal hemoglobin, and can enucleate. We conclude that hESC-derived erythropoiesis closely mimics early human development because the first 2 human hemoglobin switches are recapitulated, and because yolk sac-like and fetal liver-like cells are sequentially produced. Development of a method that yields erythroid cells with an adult phenotype remains necessary, because the most mature cells that can be produced with current systems express less than 2% adult beta-globin mRNA.

Biomechanics and biorheology of red blood cells in sickle cell anemia

PubMed Central

Li, Xuejin; Dao, Ming; Lykotrafitis, George; Karniadakis, George Em

2017-01-01

Sickle cell anemia (SCA) is an inherited blood disorder that causes painful crises due to vaso-occlusion of small blood vessels. The primary cause of the clinical phenotype of SCA is the intracellular polymerization of sickle hemoglobin resulting in sickling of red blood cells (RBCs) in deoxygenated conditions. In this review, we discuss the biomechanical and biorheological characteristics of sickle RBCs and sickle blood as well as their implications toward a better understanding of the pathophysiology and pathogenesis of SCA. Additionally, we highlight the adhesive heterogeneity of RBCs in SCA and their specific contribution to vaso-occlusive crisis. PMID:27876368

The effect of some medical treatments of thalassemia on the red blood cells

NASA Astrophysics Data System (ADS)

Zhang, Xiufang; Shen, Linming; Bao, Hongxia; Din, Xiaolan; Wang, Rongxin; Liu, Yuanyuan; Gao, Naifei; Huang, Youwen

1992-04-01

The Mössbauer spectroscopy (MS) and circular dichroism (CD) measurements have been used to investigate the effect of some medical treatments on the red blood cells (RBCs) of the patients with HbH discase and β-thalassemia (Thal.) major, respectively. The results indicate that both splenectomy and treatment with myleran are effective to alleviate the symptoms of anemia for some patients, but both of them are different in the effect on the RBCs of the patients. On the basis of the results, a hypothesis on the course of denaturation in hemoglobin (Hb) of the patients is proposed.

Autonomic nervous system involvement in sickle cell disease.

PubMed

Coates, Thomas D; Chalacheva, Patjanaporn; Zeltzer, Lonnie; Khoo, Michael C K

2018-01-01

Sickle cell disease (SCD) is a genetic disorder of hemoglobin producing hemoglobin-S (HbS) and resulting in recurrent severe episodes of pain, organ damage and premature death due to vaso- occlusion. Deoxy HbS polymerizes, causing red cells to become rigid and lodge in the microvasculature if they do not escape into larger vessels before this transformation occurs. The mechanism that triggers this transition from steady state to vaso-occlusive crisis (VOC) is not known. Patients state that cold, emotional stress, and pain itself can trigger these events. In spite of the connection between these symptoms and the autonomic nervous system (ANS), and the fact that the ANS regulates regional microvascular blood flow, the role of the ANS in sickle pathophysiology has not been significantly investigated. We will briefly review the mechanism of SCD vaso-occlusion, the dysautonomia associated with SCD and sickle trait, and the role that the ANS may play in the genesis of sickle vaso-occlusive crisis.

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

C-Window Peaks on CE-HPLC are Extremely Rare in Northern India, and Only Infrequently Represent HbC.

PubMed

Dass, Jasmita; Mittal, Suchi; Saraf, Amrita; Kotwal, Jyoti

2018-01-01

Hemoglobin C (HbC, HBB:c.19G > A) is a structural variant that has been reported rarely from India. This was a retrospective review of all high performance liquid chromatography (HPLCs) submitted over a 14 year period to a tertiary care center in North India with an aim of finding hemoglobins that elute in the C-window. Of the 32,364 HPLCs screened, 6 cases showed peaks in the C-window. Of these 6 cases, only two cases contained hemoglobin C. These was one case each of HbC/β thalassemia and compound heterozygosity for HbC and HbD. There were 4 cases which showed very similar red cell indices and chromatograms with multiple peaks eluting in D-window, C-window and an additional peak with a retention time of 4.74 min. These four cases were compound heterozygous for an α chain variant HbQ-India and a β-chain variant HbD.

The ratio of hemoglobin to red cell distribution width as a novel prognostic parameter in esophageal squamous cell carcinoma: a retrospective study from southern China

PubMed Central

Bi, Xiwen; Yang, Hang; An, Xin; Wang, Fenghua; Jiang, Wenqi

2016-01-01

Background We propose a novel prognostic parameter for esophageal squamous cell carcinoma (ESCC)—hemoglobin/red cell distribution width (HB/RDW) ratio. Its clinical prognostic value and relationship with other clinicopathological characteristics were investigated in ESCC patients. Results The optimal cut-off value was 0.989 for the HB/RDW ratio. The HB/RDW ratio (P= 0.035), tumor depth (P = 0.020) and lymph node status (P<0.001) were identified to be an independent prognostic factors of OS by multivariate analysis, which was validated by bootstrap resampling. Patients with a low HB/RDW ratio had a 1.416 times greater risk of dying during follow-up compared with those with a high HB/RDW (95% CI = 1.024–1.958, P = 0.035). Materials and Methods We retrospectively analyzed 362 patients who underwent curative treatment at a single institution between January 2007 and December 2008. The chi-square test was used to evaluate relationships between the HB/RDW ratio and other clinicopathological variables; the Kaplan–Meier method was used to analyze the 5-year overall survival (OS); and the Cox proportional hazards models were used for univariate and multivariate analyses of variables related to OS. Conclusion A significant association was found between the HB/RDW ratio and clinical characteristics and survival outcomes in ESCC patients. Based on these findings, we believe that the HB/RDW ratio is a novel and promising prognostic parameter for ESCC patients. PMID:27223088

Search for antisickling agents from plants.

PubMed

Dash, Bisnu Prasad; Archana, Y; Satapathy, Nibarana; Naik, Soumendra Kumar

2013-01-01

The sickle cell disease is fatal in nature. Thousands of children are dying off due to this health problem throughout the globe. Due to the rapid development of diagnosis and clinical managements such patients are living up to a respectable age. But as there is no permanent cure the patients are suffering from bone and joint pain, jaundice, hepato-splenomegaly, chronic infections etc. The main physiological complicacy is due to the polymerization of sickle hemoglobin (HbS), (sickling process) inside the red blood cell (RBC) of these patients during deoxygenating state. The change of RBC from spherical to sickle shape is due to the polymerization of mutant hemoglobin (HbS) inside the RBC and membrane distortion during anoxic condition. The mechanism and the process of sickling are very complex and multifactor in nature. To get rid from such complicacies it is necessary to suitably and accurately stop the sickling of RBC of the patients. The potential anti-sickling agents either from natural sources and/or synthetic molecules may be helpful for reducing the clinical morbidity of the patients. A lot of natural compounds from plant extracts have been tried by several workers in recent past. Most of the studies are based on in vitro red cell sickling studies and their mode of action has not been properly understood. Although, few studies have been in vivo in nature pertaining to transgenic sickle animal model, there is paucity of data on the human studies. The result of such studies although has shown some degree of success, a promising anti-sickling agent is yet to be established.

Search for antisickling agents from plants

PubMed Central

Dash, Bisnu Prasad; Archana, Y.; Satapathy, Nibarana; Naik, Soumendra Kumar

2013-01-01

The sickle cell disease is fatal in nature. Thousands of children are dying off due to this health problem throughout the globe. Due to the rapid development of diagnosis and clinical managements such patients are living up to a respectable age. But as there is no permanent cure the patients are suffering from bone and joint pain, jaundice, hepato-splenomegaly, chronic infections etc. The main physiological complicacy is due to the polymerization of sickle hemoglobin (HbS), (sickling process) inside the red blood cell (RBC) of these patients during deoxygenating state. The change of RBC from spherical to sickle shape is due to the polymerization of mutant hemoglobin (HbS) inside the RBC and membrane distortion during anoxic condition. The mechanism and the process of sickling are very complex and multifactor in nature. To get rid from such complicacies it is necessary to suitably and accurately stop the sickling of RBC of the patients. The potential anti-sickling agents either from natural sources and/or synthetic molecules may be helpful for reducing the clinical morbidity of the patients. A lot of natural compounds from plant extracts have been tried by several workers in recent past. Most of the studies are based on in vitro red cell sickling studies and their mode of action has not been properly understood. Although, few studies have been in vivo in nature pertaining to transgenic sickle animal model, there is paucity of data on the human studies. The result of such studies although has shown some degree of success, a promising anti-sickling agent is yet to be established. PMID:23922457

Testosterone-dependent sex differences in red blood cell hemolysis in storage, stress, and disease.

PubMed

Kanias, Tamir; Sinchar, Derek; Osei-Hwedieh, David; Baust, Jeffrey J; Jordan, Andrew; Zimring, James C; Waterman, Hayley R; de Wolski, Karen S; Acker, Jason P; Gladwin, Mark T

2016-10-01

Red blood cell (RBC) hemolysis represents an intrinsic mechanism for human vascular disease. Intravascular hemolysis releases hemoglobin and other metabolites that inhibit nitric oxide signaling and drive oxidative and inflammatory stress. Although these pathways are important in disease pathogenesis, genetic and population modifiers of hemolysis, including sex, have not been established. We studied sex differences in storage or stress-induced hemolysis in RBC units from the United States and Canada in 22 inbred mouse strains and in patients with sickle cell disease (SCD) using measures of hemolysis in 315 patients who had homozygous SS hemoglobin from the Walk-PHASST cohort. A mouse model also was used to evaluate posttransfusion recovery of stored RBCs, and gonadectomy was used to determine the mechanisms related to sex hormones. An analysis of predisposition to hemolysis based on sex revealed that male RBCs consistently exhibit increased susceptibility to hemolysis compared with females in response to routine cold storage, under osmotic or oxidative stress, after transfusion in mice, and in patients with SCD. The sex difference is intrinsic to the RBC and is not mediated by plasmatic factors or female sex hormones. Importantly, orchiectomy in mice improves RBC storage stability and posttransfusion recovery, whereas testosterone repletion therapy exacerbates hemolytic response to osmotic or oxidative stress. Our findings suggest that testosterone increases susceptibility to hemolysis across human diseases, suggesting that male sex may modulate clinical outcomes in blood storage and SCD and establishing a role for donor genetic variables in the viability of stored RBCs and in human hemolytic diseases. © 2016 AABB.

Temperature transition of human hemoglobin at body temperature: effects of calcium.

PubMed Central

Kelemen, C; Chien, S; Artmann, G M

2001-01-01

We studied the effects of calcium ion concentration on the temperature dependence of rheological behavior of human red blood cells (RBCs) and concentrated hemoglobin solutions. Our previous study (G. M. Artmann, C. Kelemen, D. Porst, G. Büldt, and S. Chien, 1998, Biophys. J., 75:3179-3183) showed a critical temperature (Tc) of 36.4 +/- 0.3 degrees C at which the RBCs underwent a transition from non-passage to passage through 1.3 microm micropipettes in response to an aspiration pressure of -2.3 kPa. An increase in intracellular Ca2+ concentration by using the ionophore A23187 reduced the passability of intact RBCs through small micropipettes above T(c); the micropipette diameter needed for >90% passage increased to 1.7 microm. Viscometry of concentrated hemoglobin solutions (45 and 50 g/dl) showed a sudden viscosity transition at 36 +/- 1 degrees C (Tc(eta)) at all calcium concentrations investigated. Below Tc(eta), the viscosity value of the concentrated hemoglobin solution at 1.8 mM Ca(2+) was higher than that at other concentrations (0.2 microM, 9 mM, and 18 mM). Above Tc(eta), the viscosity was almost Ca2+ independent. At 1.8 mM Ca2+ and 36 +/- 1 degrees C, the activation energy calculated from the viscometry data showed a strong dependence on the hemoglobin concentration. We propose that the transition of rheological behavior is attributable to a high-to-low viscosity transition mediated by a partial release of the hemoglobin-bound water. PMID:11371439

Molecular cloning and characterization of adult Sparus aurata hemoglobin genes.

PubMed

Campo, Salvatore; Nastasi, Giancarlo; Fedeli, Donatella; D'Ascola, Angela; Campo, Giuseppe M; Avenoso, Angela; Ferlazzo, Alida; Calatroni, Alberto; Falcioni, Giancarlo

2010-04-01

Among Teleosts, Sparus aurata occupies a prominent place in the gastronomic and economic fields of the Mediterranean basin and other geographic districts. The knowledge of its molecular structures and functional features, such as hemoglobin, may be helpful to understand the adaptive biochemical mechanisms that allow this fish to live under extreme conditions, including fish farming. In Sparus aurata red blood cells two different alpha and one beta hemoglobin genes have been identified. The alpha1 gene codifies a putative protein of 144 amino acids, the alpha2 gene produces a protein of 143 amino acids, and the beta gene encodes a chain of 148 amino acids. Comparative analysis of various hemoglobins indicates that allosteric regulation can be modified by the substitution of one or a few key residues. The comparison of the percentage sequence differences for alpha and beta chains in fishes indicates that evolutionary relationships between different species may be helpful to understand the mechanisms of their differentiation from other vertebrates. Hemoglobin alpha and beta chains of about 50 teleostean temperate and Antarctic fishes were analyzed to build phylogenetic trees using different algorithms: the neighbor-joining method, the maximum likelihood approach, and the Bayesian inference computation. Sparus aurata alpha chains are positioned in a paraphyletic cluster, which includes the same subunit of Chrysophrys auratus and Seriola quinqueradiata, whereas the beta chain is on an homophyletic branch with that of Chrysophrys auratus. Therefore, the phylogenetic approach suggests that both Sparus aurata hemoglobin alpha genes are paralogues and may have derived from a duplication event.

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

Vitvitsky, Victor; Yadav, Pramod K.; An, Sojin

Hydrogen sulfide is a cardioprotective signaling molecule but is toxic at elevated concentrations. Red blood cells can synthesize H2S but, lacking organelles, cannot dispose of H2S via the mitochondrial sulfide oxidation pathway. We have recently shown that at high sulfide concentrations, ferric hemoglobin oxidizes H2S to a mixture of thiosulfate and iron-bound polysulfides in which the latter species predominates. Here, we report the crystal structure of human hemoglobin containing low spin ferric sulfide, the first intermediate in heme-catalyzed sulfide oxidation. The structure provides molecular insights into why sulfide is susceptible to oxidation in human hemoglobin but is stabilized against itmore » in HbI, a specialized sulfide-carrying hemoglobin from a mollusk adapted to life in a sulfide-rich environment. We have also captured a second sulfide bound at a postulated ligand entry/exit site in the α-subunit of hemoglobin, which, to the best of our knowledge, represents the first direct evidence for this site being used to access the heme iron. Hydrodisulfide, a postulated intermediate at the junction between thiosulfate and polysulfide formation, coordinates ferric hemoglobin and, in the presence of air, generated thiosulfate. At low sulfide/heme iron ratios, the product distribution between thiosulfate and iron-bound polysulfides was approximately equal. The iron-bound polysulfides were unstable at physiological glutathione concentrations and were reduced with concomitant formation of glutathione persulfide, glutathione disulfide, and H2S. Hence, although polysulfides are unlikely to be stable in the reducing intracellular milieu, glutathione persulfide could serve as a persulfide donor for protein persulfidation, a posttranslational modification by which H2S is postulated to signal.« less

Hemoglobin-based O2 carrier O2 affinity and capillary inlet pO2 are important factors that influence O2 transport in a capillary.

PubMed

Dimino, Michael L; Palmer, Andre F

2007-01-01

Hemopure (Biopure; Cambridge, MA) and PolyHeme (Northfield Laboratories; Evanston, IL) are two acellular hemoglobin-based O2 carriers (HBOCs) currently in phase III clinical trials for use as red blood cell substitutes. The most common adverse side effect that these HBOCs exhibit is increased vasoconstriction. Autoregulatory theory has been presented as a possible explanation for this physiological effect, where it is hypothesized that low-affinity HBOCs over-deliver O2 to tissues surrounding arterioles, thereby eliciting vasoconstriction. In this paper, we wanted to investigate HBOC oxygenation of tissue surrounding a capillary, which is the smallest element of the circulatory system. An a priori model has been developed in which the performance of mixtures of acellular HBOCs (synthesized by our group and others) and human red blood cells (hRBCs) has been simulated using a Krogh tissue cylinder model (KTCM) comprising a capillary surrounded by a capillary membrane and skeletal muscle tissue in cylindrical coordinates with specified tissue O2 consumption rates and Michaelis-Menten kinetics. In this study, the total hemoglobin (hRBCs and HBOCs) concentration was kept constant. The HBOCs studied possessed O2 affinities that were higher and lower compared to hRBCs (P50's spanned 5-55 mmHg), and the equilibrium binding/release of oxygen to/from the HBOCs was modeled using the Adair equation. At normoxic inlet pO2's, there was no correlation between O2 flux out of the capillary and the O2 affinity of the HBOC. However, a correlation was found between the average pO2 tension in the capillary and the O2 affinity of the HBOC. Additionally, we studied the change in the O2 equilibrium curve of HBOCs with different O2 affinities over a wide range of inlet pO2's and found that changing the inlet pO2 greatly affected which HBOC, having a unique O2 affinity, best delivered O2 to the surrounding tissue. The analysis of oxygen transport presented could lead to a better prediction of which acellular HBOC is best suited for a specific transfusion application that many times depends on the capillary inlet pO2 tension.

Hematological findings in neotropical fish Hoplias malabaricus exposed to subchronic and dietary doses of methylmercury, inorganic lead, and tributyltin chloride.

PubMed

Oliveira Ribeiro, C A; Filipak Neto, F; Mela, M; Silva, P H; Randi, M A F; Rabitto, I S; Alves Costa, J R M; Pelletier, E

2006-05-01

Hematological indices are gaining general acceptance as valuable tools in monitoring various aspects the health of fish exposed to contaminants. In this work some effects of methyl mercury (MeHg), inorganic lead (Pb2+), and tributyltin (TBT) in a tropical fish species were evaluated by hematological methods after a trophic exposition at a subchronic level. Forty-two mature individuals of the freshwater top predator fish Hoplias malabaricus were exposed to trophic doses (each 5 days) of MeHg (0.075 microg g(-1)), Pb2+ (21 microg g(-1)), and TBT (0.3 microg g(-1)) using young fish Astyanax sp. as prey vehicle. After 14 successive doses over 70 days, blood was sampled from exposed and control groups to evaluate hematological effects of metals on erythrocytes, total leukocytes and differential leukocytes counts, hematocrit, hemoglobin concentration, and red blood cell indices mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC). Transmission electron microscopy and image analysis of erythrocytes were also used to investigate some morphometric parameters. Results show no significant effects in MCH and MCHC for all tested metals, but differences were found in erythrocytes, hemoglobin, hematocrit, MCV, and white blood cells counts. The number of leukocytes was increased in the presence of MeHg, suggesting effects on the immune system. Also the MCV increased in individuals exposed to MeHg. No ultrastructural damages were observed in red blood cells but the image analysis using light microscopy revealed differences in area, elongation, and roundness of erythrocytes from individuals exposed to Pb2+ and TBT but not in the group exposed to MeHg. The present work shows that changes in hematological and blood indices could highlight some barely detectable metal effects in fish after laboratory exposure to contaminated food, but their application in field biomonitoring using H. malabaricus will need more detailed studies and a careful consideration of environmental parameters.

Red Blood Cell Susceptibility to Pneumolysin

PubMed Central

Bokori-Brown, Monika; Petrov, Peter G.; Khafaji, Mawya A.; Mughal, Muhammad K.; Naylor, Claire E.; Shore, Angela C.; Gooding, Kim M.; Casanova, Francesco; Mitchell, Tim J.; Titball, Richard W.; Winlove, C. Peter

2016-01-01

This study investigated the effect of the biochemical and biophysical properties of the plasma membrane as well as membrane morphology on the susceptibility of human red blood cells to the cholesterol-dependent cytolysin pneumolysin, a key virulence factor of Streptococcus pneumoniae, using single cell studies. We show a correlation between the physical properties of the membrane (bending rigidity and surface and dipole electrostatic potentials) and the susceptibility of red blood cells to pneumolysin-induced hemolysis. We demonstrate that biochemical modifications of the membrane induced by oxidative stress, lipid scrambling, and artificial cell aging modulate the cell response to the toxin. We provide evidence that the diversity of response to pneumolysin in diabetic red blood cells correlates with levels of glycated hemoglobin and that the mechanical properties of the red blood cell plasma membrane are altered in diabetes. Finally, we show that diabetic red blood cells are more resistant to pneumolysin and the related toxin perfringolysin O relative to healthy red blood cells. Taken together, these studies indicate that the diversity of cell response to pneumolysin within a population of human red blood cells is influenced by the biophysical and biochemical status of the plasma membrane and the chemical and/or oxidative stress pre-history of the cell. PMID:26984406

Mechanisms Linking Red Blood Cell Disorders and Cardiovascular Diseases

PubMed Central

2015-01-01

The present paper aims to review the main pathophysiological links between red blood cell disorders and cardiovascular diseases, provides a brief description of the latest studies in this area, and considers implications for clinical practice and therapy. Anemia is associated with a special risk in proatherosclerotic conditions and heart disease and became a new therapeutic target. Guidelines must be updated for the management of patients with red blood cell disorders and cardiovascular diseases, and targets for hemoglobin level should be established. Risk scores in several cardiovascular diseases should include red blood cell count and RDW. Complete blood count and hemorheological parameters represent useful, inexpensive, widely available tools for the management and prognosis of patients with coronary heart disease, heart failure, hypertension, arrhythmias, and stroke. Hypoxia and iron accumulation cause the most important cardiovascular effects of sickle cell disease and thalassemia. Patients with congenital chronic hemolytic anemia undergoing splenectomy should be monitored, considering thromboembolic and cardiovascular risk. PMID:25710019

Rheologic and hemodynamic characteristics of red cells of mouse, rat and human.

PubMed

Chen, D; Kaul, D K

1994-01-01

The present study compares hematologic, rheologic and hemodynamic characteristics of red cells from mouse, rat and human. Red cells in these species are biconcave discs that show significant differences in diameter and mean corpuscular volume (MCV). However, differences in mean corpuscular hemoglobin concentration (MCHC) are not significant. Viscosity measurement of washed red cell suspensions (in each case the medium osmolarity adjusted to match plasma osmolarity) showed significant interspecies differences at shear rates of 37.5 and 750 sec-1 as follows: Human > rat > mouse. Hemodynamic and microcirculatory behavior of these red cells was investigated in the artificially perfused ex vivo mesocecum vasculature of the rat. Hemodynamic measurements in the whole ex vivo mesocecum preparation revealed maximal increase in the peripheral resistance unit (PRU) for the human red cells followed by the rat and mouse red cells, respectively at a hematocrit (Hct) of 40%. Further, measurements of red cell velocities (Vrbc) in single arterioles of the mesocecum vasculature, during sustained perfusion with washed red cell suspensions, showed that at any given perfusion pressure (Pa), Vrbc for both mouse and rat red cells was higher than that for human red cells, while Vrbc for mouse red cells was higher than that for the rat. These results demonstrate that the microvascular flow behavior of these red cells is likely to be influenced by both physical and rheologic characteristics.

Discriminating the hemolytic risk of blood type A plasmas using the complement hemolysis using human erythrocytes (CHUHE) assay.

PubMed

Cunnion, Kenji M; Hair, Pamela S; Krishna, Neel K; Sass, Megan A; Enos, Clinton W; Whitley, Pamela H; Maes, Lanne Y; Goldberg, Corinne L

2017-03-01

The agglutination-based cross-matching method is sensitive for antibody binding to red blood cells but is only partially predictive of complement-mediated hemolysis, which is important in many acute hemolytic transfusion reactions. Here, we describe complement hemolysis using human erythrocytes (CHUHE) assays that directly evaluate complement-mediated hemolysis between individual serum-plasma and red blood cell combinations. The CHUHE assay is used to evaluate correlations between agglutination titers and complement-mediated hemolysis as well as the hemolytic potential of plasma from type A blood donors. Plasma or serum from each type A blood donor was incubated with AB or B red blood cells in the CHUHE assay and measured for free hemoglobin release. CHUHE assays for serum or plasma demonstrate a wide, dynamic range and high sensitivity for complement-mediated hemolysis for individual serum/plasma and red blood cell combinations. CHUHE results suggest that agglutination assays alone are only moderately predictive of complement-mediated hemolysis. CHUHE results also suggest that plasma from particular type A blood donors produce minimal complement-mediated hemolysis, whereas plasma from other type A blood donors produce moderate to high-level complement-mediated hemolysis, depending on the red blood cell donor. The current results indicate that the CHUHE assay can be used to assess complement-mediated hemolysis for plasma or serum from a type A blood donor, providing additional risk discrimination over agglutination titers alone. © 2016 AABB.

Stabilization of red blood cells by the plasticizer, diethylhexylphthalate.

PubMed

Horowitz, B; Stryker, M H; Waldman, A A; Woods, K R; Gass, J D; Drago, J

1985-01-01

The red blood cells of blood stored in containers made of polyvinylchloride (PVC) film are osmotically more stable and lose on average about 1/3 less hemoglobin than when blood is stored in another plastic [poly-(ethylene-co-ethyl acrylate); EEA]. The stability of uniform volumes of stored red blood cells varies directly with PVC surface area, whereas changes in EEA surface area have comparatively little or no effect. PVC contains high concentrations of the plasticizer, diethylhexylphthalate (DEHP), known to migrate into blood and to have a high potential for toxicity. To determine if DEHP could be the red cell stabilizing agent in PVC, whole blood was stored in containers made from EEA into which was incorporated varying amounts of DEHP. Incorporation of DEHP into EEA significantly reduced erythrocyte osmotic fragility (p = 0.01). The degree of reduced fragility correlated with the level of DEHP in the cell phase implicating DEHP in PVC containers as the stabilizing agent for red cells.

Association between red cell distribution width and the risk of heart events in patients with coronary artery disease.

PubMed

Li, Weimin; Li, Xiaoting; Wang, Maofeng; Ge, Xuan; Li, Feixiang; Huang, Bian; Peng, Jiren; Li, Guohong; Lu, Liang; Yu, Zhuoyuan; Ma, Jiaojiao; Xu, Liaohang; Jin, Meijuan; Si, Hongping; Wan, Rugen

2015-04-01

Red cell distribution width (RDW) has been found to be a novel prognostic biomarker in patients with coronary artery disease (CAD); however, the association between RDW and the risk of heart events in patients with CAD is yet to be fully elucidated. Thus, the aim of the present study was to determine whether an elevated RDW was associated with the Framingham risk score (FRS) in patients with CAD. Data were retrospectively collected from Affiliated Dongyang Hospital of Wenzhou Medical University (Dongyang, China). The patients had undergone a coronary angiography and their clinical data were integrated. The patients (male, 260; female, 132) were divided into two groups based on the results of the coronary angiography, namely the CAD (n=283) and control groups (n=109). The FRS was calculated for all the subjects, and complete blood count testing with biochemical measurements was performed. The mean RDW level was 13.7±1.8% in the CAD group and 13.1±1.0% in the control group, while the mean FRS was 9.0±4.9 in the CAD group and 6.4±3.9 in the control group. The RDW and FRS were significantly higher in the CAD group compared with the control group (P<0.001). No statistically significant differences were observed between the groups with regard to the hematocrit, mean corpuscular volume, platelets, glucose, urea, albumin, aspartate aminotransferase, total cholesterol, triglycerides (TG), high-density lipoprotein cholesterol, low-density lipoprotein cholesterol and N-terminal pro-brain natriuretic peptide (P>0.05). The RDW was shown to significantly correlate with the red blood cell (RBC) count ( r =-0.133, P=0.029), hemoglobin level ( r =-0.207, P=0.001) and TG level ( r =0.226, P<0.001) within the laboratory parameters, as well as the FRS ( r =0.206, P<0.001). In the stepwise multivariate linear regression, which included the RBC count, hemoglobin level, TG level and RDW, the FRS was predicted by hemoglobin ( r 2 =0.034, P=0.001), TG ( r 2 =0.059, P<0.001) and RDW ( r 2 =0.030, P=0.003) parameters. Therefore, a novel association was revealed between higher levels of RDW and an elevated FRS in patients with CAD, which raises the possibility that a simple marker, RDW, may be associated with an increased risk of heart events in CAD patients.

Anemia prevalence and risk factors in pregnant women in an urban area of Pakistan.

PubMed

Baig-Ansari, Naila; Badruddin, Salma Halai; Karmaliani, Rozina; Harris, Hillary; Jehan, Imtiaz; Pasha, Omrana; Moss, Nancy; McClure, Elizabeth M; Goldenberg, Robert L

2008-06-01

Anemia affects almost two-thirds of pregnant women in developing countries and contributes to maternal morbidity and mortality and to low birthweight. To determine the prevalence of anemia and the dietary and socioeconomic factors associated with anemia in pregnant women living in an urban community setting in Hyderabad, Pakistan. This was a prospective, observational study of 1,369 pregnant women enrolled at 20 to 26 weeks of gestation and followed to 6 weeks postpartum. A blood sample was obtained at enrollment to determine hemoglobin levels. Information on nutritional knowledge, attitudes, and practice and dietary history regarding usual food intake before and during pregnancy were obtained by trained interviewers within 1 week of enrollment. The prevalence of anemia (defined by the World Health Organization as hemoglobin < 11.0 g/dL) in these subjects was 90.5%; of these, 75.0% had mild anemia (hemoglobin from 9.0 to 10.9 g/dL) and 14.8% had moderate anemia (hemoglobin from 7.0 to 8.9 g/dL). Only 0.7% were severely anemic (hemoglobin < 7.0 g/ dL). Nonanemic women were significantly taller, weighed more, and had a higher body mass index. Multivariate analysis after adjustment for education, pregnancy history, iron supplementation, and height showed that drinking more than three cups of tea per day before pregnancy (adjusted prevalence odds ratio [aPOR], 3.2; 95% confidence interval [CI], 1.3 to 8.0), consumption of clay or dirt during pregnancy (aPOR, 3.7; 95% CI, 1.1 to 12.3), and never consuming eggs or consuming eggs less than twice a week during pregnancy (aPOR, 1.7; 95% CI, 1.1 to 2.5) were significantly associated with anemia. Consumption of red meat less than twice a week prior to pregnancy was marginally associated with anemia (aPOR, 1.2; 95% CI, 0.8 to 1.8) but was significantly associated with lower mean hemoglobin concentrations (9.9 vs. 10.0 g/dL, p = .05) during the study period. A subanalysis excluding women with mild anemia found similar associations to those of the main model, albeit even stronger. A high percentage of women at 20 to 26 weeks of pregnancy had mild to moderate anemia. Pica, tea consumption, and low intake of eggs and red meat were associated with anemia. Women of childbearing age should be provided nutritional education regarding food sources of iron, especially prior to becoming pregnant, and taught how food choices can either enhance or interfere with iron absorption.

Hematological Profile and Martial Status in Rugby Players during Whole Body Cryostimulation

PubMed Central

Lombardi, Giovanni; Lanteri, Patrizia; Porcelli, Simone; Mauri, Clara; Colombini, Alessandra; Grasso, Dalila; Zani, Viviana; Bonomi, Felice Giulio; Melegati, Gianluca; Banfi, Giuseppe

2013-01-01

Cold-based therapies are commonly applied to alleviate pain symptoms secondary to inflammatory diseases, but also to treat injuries or overuse, as done in sports rehabilitation. Whole body cryotherapy, a relatively new form of cold therapy, consists of short whole-body exposure to extremely cold air (−110°C to −140°C). Cryostimulation is gaining wider acceptance as an effective part of physical therapy to accelerate muscle recovery in rugby players. The aim of this study was to evaluate the effect of repeated cryostimulation sessions on the hematological profile and martial status markers in professional rugby players. Twenty-seven professional rugby players received 2 daily cryostimulation treatments for 7 consecutive days. Blood samples were collected before and after administration of the cryotherapic protocol and hematological profiles were obtained. No changes in the leukocyte count or composition were seen. There was a decrease in the values for erythrocytes, hematocrit, hemoglobin and mean corpuscular hemoglobin content, and an increase in mean corpuscular volume and red cell distribution width. Platelet count and mean volume remained unchanged. Serum transferrin and ferritin decreased, while soluble transferrin receptor increased. Serum iron and transferrin saturation were unchanged, as was reticulocyte count, whereas the immature reticulocyte fraction decreased substantially. In conclusion, in this sample of professional rugby players, cryostimulation modified the hematological profile, with a reduction in erythrocyte count and hemoglobinization paralleled by a change in martial status markers. PMID:23383348

Analysis of cytopenia in geriatric inpatients.

PubMed

Röhrig, G; Becker, I; Pappas, K; Polidori, M C; Schulz, R J

2018-02-01

Peripheral blood dyscrasias in older patients are repeatedly seen in geriatric clinical practice; however, there is substantial lack of data about the epidemiology, possible causes and treatment options in this patient group. Proton pump inhibitors (PPI) are extensively used in older patients and associated with leukopenia. The primary objective of this study was the assessment of encoded cytopenia prevalence in a geriatric patient cohort and the secondary objective was the assessment of putative causes and the analysis of PPI administration in patients with cytopenia. Retrospective evaluation of patients admitted to the geriatric department of a German urban hospital between 2010 and 2012. Electronic patient data were screened for encoded diagnosis of cytopenia according to the International Classification of Diseases (ICD) 10. Inclusion criteria were ICD code D69.0-9 and/or D70.0-7, age ≥60 years and exclusion criteria were no ICD code D69.0-9 and/or D70.0-7 and age <60 years. Out of 9328 screened inpatients 54 patients remained for analysis. Study parameters included hemoglobin (Hb), red blood cell count (RBC), leucocytes, platelets, mean cell volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), red cell distribution width (RDW), presence of leukopenia (<4000/µl), presence of thrombocytopenia (<140,000/µl) and presence of anemia according to the World Health Organization (WHO). Substitution of blood products, medication with PPI and potential causes for dyscrasias were evaluated based on electronic patient records. The mean age was 78.3 ± 6.5 years (27 females, 27 males), anemia was seen in 78%, leukopenia was encoded in13% and thrombocytopenia in 44.4%. In most of the patients no substitution of blood products was documented. In most of the patients (20.4%) cytopenia was attributed to either heparin-induced thrombocytopenia (HIT) or hemato-oncologic (20.4%) diseases, followed by drug association in 18.5%. In 70.8% of the study patients PPIs were administered but the indication for PPI administration remained unclear in 20.4%. The results encourage accurate assessment of blood dyscrasias and appropriate documentation as well as indication check for PPI treatment in geriatric inpatients.

Decrease in the red cell cofactor 2,3-diphosphoglycerate increases hemoglobin oxygen affinity in the hibernating brown bear Ursus arctos.

PubMed

Revsbech, Inge G; Malte, Hans; Fröbert, Ole; Evans, Alina; Blanc, Stéphane; Josefsson, Johan; Fago, Angela

2013-01-01

During winter hibernation, brown bears (Ursus arctos) reduce basal O(2) consumption rate to ∼25% compared with the active state, while body temperature decreases moderately (to ∼30°C), suggesting a temperature-independent component in their metabolic depression. To establish whether changes in O(2) consumption during hibernation correlate with changes in blood O(2) affinity, we took blood samples from the same six individuals of hibernating and nonhibernating free-ranging brown bears during winter and summer, respectively. A single hemoglobin (Hb) component was detected in all samples, indicating no switch in Hb synthesis. O(2) binding curves measured on red blood cell lysates at 30°C and 37°C showed a less temperature-sensitive O(2) affinity than in other vertebrates. Furthermore, hemolysates from hibernating bears consistently showed lower cooperativity and higher O(2) affinity than their summer counterparts, regardless of the temperature. We found that this increase in O(2) affinity was associated with a significant decrease in the red cell Hb-cofactor 2,3-diphosphoglycerate (DPG) during hibernation to approximately half of the summer value. Experiments performed on purified Hb, to which DPG had been added to match summer and winter levels, confirmed that the low DPG content was the cause of the left shift in the Hb-O(2) equilibrium curve during hibernation. Levels of plasma lactate indicated that glycolysis is not upregulated during hibernation and that metabolism is essentially aerobic. Calculations show that the increase in Hb-O(2) affinity and decrease in cooperativity resulting from decreased red cell DPG may be crucial in maintaining a fairly constant tissue oxygen tension during hibernation in vivo.

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.

Coenzyme Q supplementation in pulmonary arterial hypertension

PubMed Central

Sharp, Jacqueline; Farha, Samar; Park, Margaret M.; Comhair, Suzy A.; Lundgrin, Erika L.; Tang, W.H. Wilson; Bongard, Robert D.; Merker, Marilyn P.; Erzurum, Serpil C.

2014-01-01

Mitochondrial dysfunction is a fundamental abnormality in the vascular endothelium and smooth muscle of patients with pulmonary arterial hypertension (PAH). Because coenzyme Q (CoQ) is essential for mitochondrial function and efficient oxygen utilization as the electron carrier in the inner mitochondrial membrane, we hypothesized that CoQ would improve mitochondrial function and benefit PAH patients. To test this, oxidized and reduced levels of CoQ, cardiac function by echocardiogram, mitochondrial functions of heme synthesis and cellular metabolism were evaluated in PAH patients (N=8) in comparison to healthy controls (N=7), at baseline and after 12 weeks oral CoQ supplementation. CoQ levels were similar among PAH and control individuals, and increased in all subjects with CoQ supplementation. PAH patients had higher CoQ levels than controls with supplementation, and a tendency to a higher reduced-to-oxidized CoQ ratio. Cardiac parameters improved with CoQ supplementation, although 6-minute walk distances and BNP levels did not significantly change. Consistent with improved mitochondrial synthetic function, hemoglobin increased and red cell distribution width (RDW) decreased in PAH patients with CoQ, while hemoglobin declined slightly and RDW did not change in healthy controls. In contrast, metabolic and redox parameters, including lactate, pyruvate and reduced or oxidized gluthathione, did not change in PAH patients with CoQ. In summary, CoQ improved hemoglobin and red cell maturation in PAH, but longer studies and/or higher doses with a randomized placebo-controlled controlled design are necessary to evaluate the clinical benefit of this simple nutritional supplement. PMID:25180165

Quantitative trait locus linkage analysis in a large Amish pedigree identifies novel candidate loci for erythrocyte traits

PubMed Central

Hinckley, Jesse D; Abbott, Diana; Burns, Trudy L; Heiman, Meadow; Shapiro, Amy D; Wang, Kai; Di Paola, Jorge

2013-01-01

We characterized a large Amish pedigree and, in 384 pedigree members, analyzed the genetic variance components with covariate screen as well as genome-wide quantitative trait locus (QTL) linkage analysis of red blood cell count (RBC), hemoglobin (HB), hematocrit (HCT), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), red cell distribution width (RDW), platelet count (PLT), and white blood cell count (WBC) using SOLAR. Age and gender were found to be significant covariates in many CBC traits. We obtained significant heritability estimates for RBC, MCV, MCH, MCHC, RDW, PLT, and WBC. We report four candidate loci with Logarithm of the odds (LOD) scores above 2.0: 6q25 (MCH), 9q33 (WBC), 10p12 (RDW), and 20q13 (MCV). We also report eleven candidate loci with LOD scores between 1.5 and <2.0. Bivariate linkage analysis of MCV and MCH on chromosome 20 resulted in a higher maximum LOD score of 3.14. Linkage signals on chromosomes 4q28, 6p22, 6q25, and 20q13 are concomitant with previously reported QTL. All other linkage signals reported herein represent novel evidence of candidate QTL. Interestingly rs1800562, the most common causal variant of hereditary hemochromatosis in HFE (6p22) was associated with MCH and MCHC in this family. Linkage studies like the one presented here will allow investigators to focus the search for rare variants amidst the noise encountered in the large amounts of data generated by whole-genome sequencing. PMID:24058921

Effects of occupational exposure of X-Ray on hematological parameters of diagnostic technicians

NASA Astrophysics Data System (ADS)

Taqi, Ali H.; Faraj, Kharman A.; Zaynal, Sarah A.; Hameed, Ahmed M.; Mahmood, Abd-Alkader A.

2018-06-01

The aim of this study was to identify the effects of long term exposure of X-ray on diagnostic technicians which they work at Kirkuk hospitals through examining some hematological parameters which are white blood cells (WBC), Neutrophils, Lymphocyte, Monocyte, Eosinophil, Basophil, Reactive Lymphocyte, red blood cells (RBC), hemoglobin (Hb), hematocrit (HCT), Mean Cell Volume (MCV), Mean Corpuscular Hemoglobin (MCH), Mean Cell Hemoglobin Concentration (MCHC), Red Cell Distribution Width (RDW), Platelet (PLT). The study included 54 male diagnostic technicians and 54 male healthy controls match with the first group to show any alteration of the hematological parameters. The diagnostic technicians divided into two groups depending on their work experience and hours working per day. The statistical analysis was performed using (Graph-pad) program. Our results showed that the Complete blood cells count (CBC) parameters (Neutrophil, Monocytes, Basophile, MCV, RDW and PLT) significantly (P<.05) decreased while the parameters (Lymphocytes, RBC, Hb and HCT) significantly (P<.05) increased and strong significantly (P<.0001) increasing was recorded for the parameter Reactive lymphocytes mostly in all groups of the diagnostic technicians compared with their controls. We concluded that chronic exposure of X-ray can significantly alter some hematological parameters and the number of hours working per day has observable effects on the some hematological parameters. We recommended training and courses about hazard of ionizing radiation should be organized for enhance the healthcare quality of the technicians and to improve their knowledge about benefit of radiation protection tools to protect themselves from any overexposure during the daily life.

Sickle red cell dehydration: mechanisms and interventions.

PubMed

Bookchin, Robert M; Lew, Virgilio L

2002-03-01

A critical link between the single molecular defect in sickle cell anemia and the extensive pathology of this disease is the reversible increase in red cell membrane permeability generated by hemoglobin S polymers in the deoxygenated state. This permeability, usually described as P (sickle), triggers a chain of events in which two constitutive transporters of the red cell membrane become activated-the recently cloned intermediate conductance, Ca 2+ -sensitive K channel, and the electroneutral K:Cl cotransporter-leading to sickle cell dehydration. This article reviews knowledge of the dehydration mechanism, stressing the marked heterogeneity of dehydration rates in sickle cell populations, and discusses recent contributions to understanding of the function and regulation of P (sickle), Ca 2+ -sensitive K channel, and K:Cl cotransporter, and of therapies targeted at these transporters.

A Hemoglobin Based Oxygen Carrier, Bovine Polymerized Hemoglobin (HBOC-201) versus Hetastarch (HEX) in an Uncontrolled Liver Injury Hemorrhagic Shock Swine Model with Delayed Evacuation

DTIC Science & Technology

2004-10-01

A Hemoglobin Based Oxygen Carrier, Bovine Polymerized Hemoglobin (HBOC-201) versus Hetastarch (HEX) in an Uncontrolled Liver Injury Hemorrhagic Shock...Transcutaneous tis- sue oxygenation was restored more rap- idly in HBOC-201 pigs, there was a trend to lower lactic acid, and base deficit was less...lactic acidosis and base deficit (BD) abnormalities, indicating on-going hypoperfusion.2–4 As these abnormalities measured upon hospital arrival

Health Risk Assessment of Women in Submarines: Reproductive and Developmental Toxicity Evaluation of Major Submarine Atmosphere Components (CO, CO2 and O2) in Rats (Rattus norvegicus) - Phase II (Neurological and Reproductive Performance Study)

DTIC Science & Technology

2011-10-11

exposed parents. Statistically significant increases in hematopoietic activity (mild polycythemia , leukocytosis and thrombocytosis) were...Tables 25 & 26). Polycythemia (increased red blood cells, with expected increases in hemoglobin and hematocrit) is an established effect of

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.

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

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

An integrated photo-thermal sensing system for rapid and direct diagnosis of anemia.

PubMed

Kwak, Bong Seop; Kim, Hyung Joon; Kim, Hyun Ok; Jung, Hyo-Il

2010-12-15

This article presents a thermal biosensor to diagnose the anemia without chemical treatments using temperature increase of red blood cells (RBC) when hemoglobin molecules absorb specific wavelength of photons and convert them to thermal energy. For measuring temperature change of red blood cell, the micro-scaled platinum resistance temperature detector (Pt RTD) was developed. For maintenance of constant ambient temperature, we designed and fabricated a thermostat system. The thermostat system consists of a K-type thermocouple and two electric heaters that serve to increase the system temperature, which is monitored by the thermocouple. Both heaters and the thermocouple were connected to a proportional-integral-derivative (PID) controller and enabled to maintain the temperature constant (<±0.1°C). For specific heating of red blood cell, 8.0 W/cm(2) diode pumped solid state (DPSS) continuous wave (CW) laser module was used with 532 nm wavelength. Using this system, we successfully measured the temperature variations (from 66.33±2.72°C to 74.16±2.06°C) of whole blood samples from 10 anemic patients and subsequently determined the concentration of hemoglobin (from 7.2 g/dL to 9.8 g/dL). The method proposed in this paper requires significantly less amount of whole blood sample (6 μl) compared with the conventional methods (175 μl) and allows instantaneous diagnosis (3 s) of anemia. Copyright © 2010 Elsevier B.V. All rights reserved.

Relationship among circulating hemoglobin, nitric oxide synthase activities and angiogenic poise in red- and white-blooded Antarctic notothenioid fishes.

PubMed

Beers, Jody M; Borley, Kimberly A; Sidell, Bruce D

2010-08-01

Nitric oxide (NO)-mediated angiogenesis may play a role in establishing dense retinal vasculatures of Antarctic hemoglobinless icefishes (suborder: Notothenioidei). We hypothesized that loss of hemoglobin (Hb) leads to elevation in [NO] due to decreased degradation of the compound when the NO-scavenger Hb is absent, thereby inducing vascular growth. We found that total mass of NO metabolites, nitrite plus nitrate (NO(x)), in plasma is greater in icefishes than in red-blooded notothenioids [e.g. C. aceratus (Hb-), 22.7+/-2.9 microM; N. coriiceps (Hb+), 14.7+/-1.7 microM], suggesting a higher NO load in hemoglobinless animals. High NO levels do not appear to be a result of greater NO synthesis; we consistently measured lower activities of the enzyme catalyzing NO production, nitric oxide synthase, in tissues of icefishes than in Hb-expressing notothenioids [e.g. 96+/-10 and 216+/-39 pmol(min g wet wt)(-1) in brain tissue of C. aceratus (Hb-) and G. gibberifrons (Hb+), respectively]. Levels of mRNA for hypoxia-induced (HIF-1alpha and PHD2) and angiogenic genes (VEGF) were similar in red- and white-blooded species, indicating that vascular maintenance in adult animals does not require differences in angiogenic tone. This does not preclude a cause-and-effect relationship between absence of Hb and NO-mediated angiogenesis during earlier ontogenetic stages of icefishes. Copyright (c) 2010 Elsevier Inc. All rights reserved.

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.

Mechanisms of Human Erythrocytic Bioactivation of Nitrite*

PubMed Central

Liu, Chen; Wajih, Nadeem; Liu, Xiaohua; Basu, Swati; Janes, John; Marvel, Madison; Keggi, Christian; Helms, Christine C.; Lee, Amber N.; Belanger, Andrea M.; Diz, Debra I.; Laurienti, Paul J.; Caudell, David L.; Wang, Jun; Gladwin, Mark T.; Kim-Shapiro, Daniel B.

2015-01-01

Nitrite signaling likely occurs through its reduction to nitric oxide (NO). Several reports support a role of erythrocytes and hemoglobin in nitrite reduction, but this remains controversial, and alternative reductive pathways have been proposed. In this work we determined whether the primary human erythrocytic nitrite reductase is hemoglobin as opposed to other erythrocytic proteins that have been suggested to be the major source of nitrite reduction. We employed several different assays to determine NO production from nitrite in erythrocytes including electron paramagnetic resonance detection of nitrosyl hemoglobin, chemiluminescent detection of NO, and inhibition of platelet activation and aggregation. Our studies show that NO is formed by red blood cells and inhibits platelet activation. Nitric oxide formation and signaling can be recapitulated with isolated deoxyhemoglobin. Importantly, there is limited NO production from erythrocytic xanthine oxidoreductase and nitric-oxide synthase. Under certain conditions we find dorzolamide (an inhibitor of carbonic anhydrase) results in diminished nitrite bioactivation, but the role of carbonic anhydrase is abrogated when physiological concentrations of CO2 are present. Importantly, carbon monoxide, which inhibits hemoglobin function as a nitrite reductase, abolishes nitrite bioactivation. Overall our data suggest that deoxyhemoglobin is the primary erythrocytic nitrite reductase operating under physiological conditions and accounts for nitrite-mediated NO signaling in blood. PMID:25471374

Reduced iron parameters and cognitive processes in children and adolescents with DM1 compared to those with standard parameters.

PubMed

Mojs, Ewa; Stanisławska-Kubiak, Maia; Wójciak, Rafał W; Wojciechowska, Julita; Przewoźniak, Sabina

2016-03-01

Anemia in patients with diabetes is not scarce and may contribute to the complications of the disease. The risk of iron deficiency parameters in child sufferers of diabetes type 1, observed in studies, can lead to cognitive impairment. The aim of the study was to determine whether children and adolescents with diabetes type 1, in whom reduced ferric parameters are observed in control tests, may also show reduced cognitive performance. The study included 100 children with diabetes type 1 at the age of 6-17 years. During control tests, patients' morphological blood parameters were measured: red blood cells (RBC), hemoglobin, glycosylated hemoglobin, hematocrit, RBC volume, the molar mass of hemoglobin in RBC (MCH), mean corpuscular hemoglobin in RBC and iron concentrations in serum using flame atomic absorption spectroscopy and the Wechsler Intelligence Scale for Children (WISC-R). Results in the group of children with a diabetes type 1 significantly lower concentration of three ferric parameters affect the non-verbal intelligence measured with WISC-R. The prevalence of reduced ferric parameters justifies further screening in all children with diabetes type 1 and taking up appropriate preventive measures to reduce the risk of their occurrence. Copyright © 2016 American Federation for Medical Research.

[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.

Biomechanics and biorheology of red blood cells in sickle cell anemia.

PubMed

Li, Xuejin; Dao, Ming; Lykotrafitis, George; Karniadakis, George Em

2017-01-04

Sickle cell anemia (SCA) is an inherited blood disorder that causes painful crises due to vaso-occlusion of small blood vessels. The primary cause of the clinical phenotype of SCA is the intracellular polymerization of sickle hemoglobin resulting in sickling of red blood cells (RBCs) in deoxygenated conditions. In this review, we discuss the biomechanical and biorheological characteristics of sickle RBCs and sickle blood as well as their implications toward a better understanding of the pathophysiology and pathogenesis of SCA. Additionally, we highlight the adhesive heterogeneity of RBCs in SCA and their specific contribution to vaso-occlusive crisis. Copyright © 2016 Elsevier Ltd. All rights reserved.

INCREASED BLOOD VOLUME IN POLYCYTHEMIA VERA AND THE EFFECT ON IT OF TREATMENT WITH P$sup 3$$sup 2$

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

Burger, T.; Keszthelyi, B.; Peer, J.

1961-01-01

The effect of this treatment was studied in 3 patients with polycythemia vera having hematocrits of 70-80% and red cell counts of 6-8 x 10/sup 6/. Plasma volume was also elevated and the red cell volume was decreased to 80-5 mu m/sup 3/ from a normal mean of 87. After a single injection of 3-10 mc inorganic P/sup 32/O/sub 4/, subjective symptoms improved as well as the hematologic values. Hematocrit, hemoglobin, and counts of erythrocytes, leukocytes, and thrombocytes fell. Blood volume and viscosity also declined. (H.H.D.)

Population-based screening for anemia using first-time blood donors

PubMed Central

Mast, Alan E.; Steele, Whitney R.; Johnson, Bryce; Wright, David J.; Cable, Ritchard G.; Carey, Patricia; Gottschall, Jerome L.; Kiss, Joseph E.; Simon, Toby L.; Murphy, Edward L.

2012-01-01

Background Anemia is an important public health concern. Data from population-based surveys such as the National Health and Nutrition Examination Survey (NHANES) are the gold standard, but are obtained infrequently and include only small samples from certain minority groups. Objectives We assessed whether readily available databases of blood donor hemoglobin values could be used as a surrogate for population hemoglobin values from NHANES. Design Blood donor venous and fingerstick hemoglobin values were compared to 10,254 NHANES 2005-2008 venous hemoglobin values using demographically stratified analyses and ANOVA. Fingerstick hemoglobins or hematocrits were converted to venous hemoglobin estimates using regression analysis. Results Venous hemoglobin values from 1,609 first time donors correlated extremely well with NHANES data across different age, gender and demographic groups. Cigarette smoking increased hemoglobin by 0.26 to 0.59 g/dL depending on intensity. Converted fingerstick hemoglobin from 36,793 first time donors agreed well with NHANES hemoglobin (weighted mean hemoglobin of 15.53 g/dL for donors and 15.73 g/dL for NHANES) with similar variation in mean hemoglobin by age. However, compared to NHANES, the larger donor dataset showed reduced differences in mean hemoglobin between Blacks and other races/ethnicities. Conclusions Overall, first-time donor fingerstick hemoglobins approximate U.S. population data and represent a readily available public health resource for ongoing anemia surveillance. PMID:22460662

Molecular controls of the oxygenation and redox reactions of hemoglobin.

PubMed

Bonaventura, Celia; Henkens, Robert; Alayash, Abdu I; Banerjee, Sambuddha; Crumbliss, Alvin L

2013-06-10

The broad classes of O(2)-binding proteins known as hemoglobins (Hbs) carry out oxygenation and redox functions that allow organisms with significantly different physiological demands to exist in a wide range of environments. This is aided by allosteric controls that modulate the protein's redox reactions as well as its O(2)-binding functions. The controls of Hb's redox reactions can differ appreciably from the molecular controls for Hb oxygenation and come into play in elegant mechanisms for dealing with nitrosative stress, in the malarial resistance conferred by sickle cell Hb, and in the as-yet unsuccessful designs for safe and effective blood substitutes. An important basic principle in consideration of Hb's redox reactions is the distinction between kinetic and thermodynamic reaction control. Clarification of these modes of control is critical to gaining an increased understanding of Hb-mediated oxidative processes and oxidative toxicity in vivo. This review addresses emerging concepts and some unresolved questions regarding the interplay between the oxygenation and oxidation reactions of structurally diverse Hbs, both within red blood cells and under acellular conditions. Developing methods that control Hb-mediated oxidative toxicity will be critical to the future development of Hb-based blood substitutes.

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

Early resuscitation with polymerized bovine hemoglobin reverses acidosis, but not peripheral tissue oxygenation, in a severe hamster shock model.

PubMed

Wettstein, Reto; Tsai, Amy G; Harder, Yves; Erni, Dominique; Intaglietta, Marcos

2006-11-01

Awake hamsters equipped with the dorsal window chamber preparation were subjected to hemorrhage of 50% of the estimated blood volume. Initial resuscitation (25% of estimated blood volume) with polymerized bovine hemoglobin (PBH) or 10% hydroxyethyl starch (HES) occurred in concert with an equivolumetric bleeding to simulate the early, prehospital setting (exchange transfusion). Resuscitation (25% of estimated blood volume) without bleeding was performed with PBH, HES, or autologous red blood cells (HES-RBCs). Peripheral microcirculation, tissue oxygenation, and systemic hemodynamic and blood gas parameters were assessed. After exchange transfusion, base deficit was -8.6 +/- 3.7 mmol/L (PBH) and -5.1 +/- 5.3 mmol/L (HES) (not significant). Functional capillary density was 17% +/- 6% of baseline (PBH) and 31% +/- 11% (HES) (P < 0.05) and arteriolar diameter 73% +/- 3% of baseline (PBH) and 90% + 5% (HES) (P < 0.01). At the end, hemoglobin levels were 3.7 +/- 0.3 g/dL with HES, 8.2 +/- 0.6 g/dL with PBH, and 10.4 +/- 0.8 g/dL with HES-RBCs (P < 0.01 HES vs. PBH and HES-RBCs, P < 0.05 PBH vs. HES-RBCs). Base excess was restored to baseline with PBH and HES-RBCs, but not with HES (P < 0.05). Functional capillary density was 46% +/- 5% of baseline (PBH), 62% + 20% (HES-RBCs), and 36% +/- 19% (HES) (P < 0.01 HES-RBCs vs. HES). Peripheral oxygen delivery and consumption was highest with HES-RBCs, followed by PBH (P < 0.05 HES-RBCs vs. PBH, P < 0.01 HES-RBCs and PBH vs. HES). In conclusion, the PBH led to a correction of base deficit comparable to blood transfusion. However, oxygenation of the peripheral tissue was inferior with PBH. This was attributed to its negative impact on the peripheral microcirculation caused by arteriolar vasoconstriction.

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

Swarup, S.; Chatterjea, J.B.; Hosain, P.

Several Hb. E-thalassemia and a few other cases of hematological interest were subjected to radio-iron tests using tracer doses of only 0.035 plus or minus 0.005 mu c/kg. of bodyweight and gas-flow counter for assaying the radio-activity of the samples. Serum iron and hemoglobin iron concentrations; curves for plasma iron clearance and appearance of radio-iron in red cells, and the plasma iron and the red cell iron turnover rates were obtained by standard methods. The results showed an increased rate of plasma clearance but decreased utilization of iron by erythrocytes in Hb. E-thalassemia disease; plasma iron-clearance pattern was similar tomore » iron deficiency anemia but the red cell radio-iron uptake pattern bore similarity to aplastic anemia. This suggests that ineffective erythropoiesis contributes significantly to the causation of anemia in Hb. E-thalassemia disease. (auth)« less

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.

Restrictive or Liberal Red-Cell Transfusion for Cardiac Surgery.

PubMed

Mazer, C David; Whitlock, Richard P; Fergusson, Dean A; Hall, Judith; Belley-Cote, Emilie; Connolly, Katherine; Khanykin, Boris; Gregory, Alexander J; de Médicis, Étienne; McGuinness, Shay; Royse, Alistair; Carrier, François M; Young, Paul J; Villar, Juan C; Grocott, Hilary P; Seeberger, Manfred D; Fremes, Stephen; Lellouche, François; Syed, Summer; Byrne, Kelly; Bagshaw, Sean M; Hwang, Nian C; Mehta, Chirag; Painter, Thomas W; Royse, Colin; Verma, Subodh; Hare, Gregory M T; Cohen, Ashley; Thorpe, Kevin E; Jüni, Peter; Shehata, Nadine

2017-11-30

The effect of a restrictive versus liberal red-cell transfusion strategy on clinical outcomes in patients undergoing cardiac surgery remains unclear. In this multicenter, open-label, noninferiority trial, we randomly assigned 5243 adults undergoing cardiac surgery who had a European System for Cardiac Operative Risk Evaluation (EuroSCORE) I of 6 or more (on a scale from 0 to 47, with higher scores indicating a higher risk of death after cardiac surgery) to a restrictive red-cell transfusion threshold (transfuse if hemoglobin level was <7.5 g per deciliter, starting from induction of anesthesia) or a liberal red-cell transfusion threshold (transfuse if hemoglobin level was <9.5 g per deciliter in the operating room or intensive care unit [ICU] or was <8.5 g per deciliter in the non-ICU ward). The primary composite outcome was death from any cause, myocardial infarction, stroke, or new-onset renal failure with dialysis by hospital discharge or by day 28, whichever came first. Secondary outcomes included red-cell transfusion and other clinical outcomes. The primary outcome occurred in 11.4% of the patients in the restrictive-threshold group, as compared with 12.5% of those in the liberal-threshold group (absolute risk difference, -1.11 percentage points; 95% confidence interval [CI], -2.93 to 0.72; odds ratio, 0.90; 95% CI, 0.76 to 1.07; P<0.001 for noninferiority). Mortality was 3.0% in the restrictive-threshold group and 3.6% in the liberal-threshold group (odds ratio, 0.85; 95% CI, 0.62 to 1.16). Red-cell transfusion occurred in 52.3% of the patients in the restrictive-threshold group, as compared with 72.6% of those in the liberal-threshold group (odds ratio, 0.41; 95% CI, 0.37 to 0.47). There were no significant between-group differences with regard to the other secondary outcomes. In patients undergoing cardiac surgery who were at moderate-to-high risk for death, a restrictive strategy regarding red-cell transfusion was noninferior to a liberal strategy with respect to the composite outcome of death from any cause, myocardial infarction, stroke, or new-onset renal failure with dialysis, with less blood transfused. (Funded by the Canadian Institutes of Health Research and others; TRICS III ClinicalTrials.gov number, NCT02042898 .).

Veterinary Research Manpower Development for Defense

DTIC Science & Technology

2013-09-01

combination of Newcastle Disease (ND) control and improved husbandry practices shows promise as a means to improve the nutrition and overall quality of...of antibiotic resistance.  T. gondii seropositive cats had significantly lower levels of hemoglobin , red blood cell counts, and hematocrit (Pɘ.05...dogs.  The body condition scores of captive elephants declined after the age of 40 years suggesting that the nutritional needs of older

Hematologic responses to hypobaric hyperoxia.

NASA Technical Reports Server (NTRS)

Larkin, E. C.; Adams, J. D.; Williams, W. T.; Duncan, D. M.

1972-01-01

Study of the effects of hypoxia, activity, and G forces on human hematopoiesis in an attempt to elucidate these phenomena more precisely. Eight subjects were exposed to an atmosphere of 100% O2 at 258 mm Hg for 30 days, and thereafter immediately exposed to transverse G forces, simulating the Gemini flights' reentry profile. All subjects displayed a significant continuous decline in red cell mass during the exposure period, as measured by the carbon monoxide-dilution method. The Cr51 method also indicated a decline in red blood corpuscle mass. The decrease in red cell mass was due to suppression of erythropoiesis and to hemolysis. After exposure to hyperoxia, all subjects exhibited elevated plasma hemoglobin levels, decreased reticulocyte counts, and decreased red cell survivals. CO production rates and urine erythropoietin levels were unchanged. Two hours after termination of exposure to hyperoxia, all subjects exhibited increased reticulocyte counts which were sustained for longer than two weeks. The progressive decrease in red cell mass was promptly arrested on return to ground level atmospheres. Within 116 days after exposure to hyperoxia, the hematologic parameters of all eight subjects had returned to control levels.

Network simulation-based optimization of centrifugo-pneumatic blood plasma separation

PubMed Central

Zehnle, S.; Zengerle, R.; von Stetten, F.; Paust, N.

2017-01-01

Automated and robust separation of 14 μl of plasma from 40 μl of whole blood at a purity of 99.81% ± 0.11% within 43 s is demonstrated for the hematocrit range of 20%–60% in a centrifugal microfluidic polymer disk. At high rotational frequency, red blood cells (RBCs) within whole blood are concentrated in a radial outer RBC collection chamber. Simultaneously, plasma is concentrated in a radial inner pneumatic chamber, where a defined air volume is enclosed and compressed. Subsequent reduction of the rotational frequency to not lower than 25 Hz enables rapid transfer of supernatant plasma into a plasma collection chamber, with highly suppressed resuspension of red blood cells. Disk design and the rotational protocol are optimized to make the process fast, robust, and insusceptible for undesired cell resuspension. Numerical network simulation with lumped model elements is used to predict and optimize the fluidic characteristics. Lysis of the remaining red blood cells in the purified plasma, followed by measurement of the hemoglobin concentration, was used to determine plasma purity. Due to the pneumatic actuation, no surface treatment of the fluidic cartridge or any additional external means are required, offering the possibility for low-cost mass fabrication technologies, such as injection molding or thermoforming. PMID:28798850

Donor preoperative oxygen delivery and post-extubation hypoxia impact donation after circulatory death hypoxic cholangiopathy.

PubMed

Chirichella, Thomas J; Dunham, C Michael; Zimmerman, Michael A; Phelan, Elise M; Mandell, M Susan; Conzen, Kendra D; Kelley, Stephen E; Nydam, Trevor L; Bak, Thomas E; Kam, Igal; Wachs, Michael E

2016-03-28

To evaluate donation after circulatory death (DCD) orthotopic liver transplant outcomes [hypoxic cholangiopathy (HC) and patient/graft survival] and donor risk-conditions. From 2003-2013, 45 DCD donor transplants were performed. Predonation physiologic data from UNOS DonorNet included preoperative systolic and diastolic blood pressure, heart rate, pH, SpO2, PaO2, FiO2, and hemoglobin. Mean arterial blood pressure was computed from the systolic and diastolic blood pressures. Donor preoperative arterial O2 content was computed as [hemoglobin (gm/dL) × 1.37 (mL O2/gm) × SpO2%) + (0.003 × PaO2)]. The amount of preoperative donor red blood cell transfusions given and vasopressor use during the intensive care unit stay were documented. Donors who were transfused ≥ 1 unit of red-cells or received ≥ 2 vasopressors in the preoperative period were categorized as the red-cell/multi-pressor group. Following withdrawal of life support, donor ischemia time was computed as the number-of-minutes from onset of diastolic blood pressure < 60 mmHg until aortic cross clamping. Donor hypoxemia time was the number-of-minutes from onset of pulse oximetry < 80% until clamping. Donor hypoxia score was (ischemia time + hypoxemia time) ÷ donor preoperative hemoglobin. The 1, 3, and 5 year graft and patient survival rates were 83%, 77%, 60%; and 92%, 84%, and 72%, respectively. HC occurred in 49% with 16% requiring retransplant. HC occurred in donors with increased age (33.0 ± 10.6 years vs 25.6 ± 8.4 years, P = 0.014), less preoperative multiple vasopressors or red-cell transfusion (9.5% vs 54.6%, P = 0.002), lower preoperative hemoglobin (10.7 ± 2.2 gm/dL vs 12.3 ± 2.1 gm/dL, P = 0.017), lower preoperative arterial oxygen content (14.8 ± 2.8 mL O2/100 mL blood vs 16.8 ± 3.3 mL O2/100 mL blood, P = 0.049), greater hypoxia score >2.0 (69.6% vs 25.0%, P = 0.006), and increased preoperative mean arterial pressure (92.7 ± 16.2 mmHg vs 83.8 ± 18.5 mmHg, P = 0.10). HC was independently associated with age, multi-pressor/red-cell transfusion status, arterial oxygen content, hypoxia score, and mean arterial pressure (r(2) = 0.6197). The transplantation rate was greater for the later period with more liberal donor selection [era 2 (7.1/year)], compared to our early experience [era 1 (2.5/year)]. HC occurred in 63.0% during era 2 and in 29.4% during era 1 (P = 0.03). Era 2 donors had longer times for extubation-to-asystole (14.4 ± 4.7 m vs 9.3 ± 4.5 m, P = 0.001), ischemia (13.9 ± 5.9 m vs 9.7 ± 5.6 m, P = 0.03), and hypoxemia (16.0 ± 5.1 m vs 11.1 ± 6.7 m, P = 0.013) and a higher hypoxia score > 2.0 rate (73.1% vs 28.6%, P = 0.006). Easily measured donor indices, including a hypoxia score, provide an objective measure of DCD liver transplantation risk for recipient HC. Donor selection criteria influence HC rates.

Donor preoperative oxygen delivery and post-extubation hypoxia impact donation after circulatory death hypoxic cholangiopathy

PubMed Central

Chirichella, Thomas J; Dunham, C Michael; Zimmerman, Michael A; Phelan, Elise M; Mandell, M Susan; Conzen, Kendra D; Kelley, Stephen E; Nydam, Trevor L; Bak, Thomas E; Kam, Igal; Wachs, Michael E

2016-01-01

AIM: To evaluate donation after circulatory death (DCD) orthotopic liver transplant outcomes [hypoxic cholangiopathy (HC) and patient/graft survival] and donor risk-conditions. METHODS: From 2003-2013, 45 DCD donor transplants were performed. Predonation physiologic data from UNOS DonorNet included preoperative systolic and diastolic blood pressure, heart rate, pH, SpO2, PaO2, FiO2, and hemoglobin. Mean arterial blood pressure was computed from the systolic and diastolic blood pressures. Donor preoperative arterial O2 content was computed as [hemoglobin (gm/dL) × 1.37 (mL O2/gm) × SpO2%) + (0.003 × PaO2)]. The amount of preoperative donor red blood cell transfusions given and vasopressor use during the intensive care unit stay were documented. Donors who were transfused ≥ 1 unit of red-cells or received ≥ 2 vasopressors in the preoperative period were categorized as the red-cell/multi-pressor group. Following withdrawal of life support, donor ischemia time was computed as the number-of-minutes from onset of diastolic blood pressure < 60 mmHg until aortic cross clamping. Donor hypoxemia time was the number-of-minutes from onset of pulse oximetry < 80% until clamping. Donor hypoxia score was (ischemia time + hypoxemia time) ÷ donor preoperative hemoglobin. RESULTS: The 1, 3, and 5 year graft and patient survival rates were 83%, 77%, 60%; and 92%, 84%, and 72%, respectively. HC occurred in 49% with 16% requiring retransplant. HC occurred in donors with increased age (33.0 ± 10.6 years vs 25.6 ± 8.4 years, P = 0.014), less preoperative multiple vasopressors or red-cell transfusion (9.5% vs 54.6%, P = 0.002), lower preoperative hemoglobin (10.7 ± 2.2 gm/dL vs 12.3 ± 2.1 gm/dL, P = 0.017), lower preoperative arterial oxygen content (14.8 ± 2.8 mL O2/100 mL blood vs 16.8 ± 3.3 mL O2/100 mL blood, P = 0.049), greater hypoxia score >2.0 (69.6% vs 25.0%, P = 0.006), and increased preoperative mean arterial pressure (92.7 ± 16.2 mmHg vs 83.8 ± 18.5 mmHg, P = 0.10). HC was independently associated with age, multi-pressor/red-cell transfusion status, arterial oxygen content, hypoxia score, and mean arterial pressure (r2 = 0.6197). The transplantation rate was greater for the later period with more liberal donor selection [era 2 (7.1/year)], compared to our early experience [era 1 (2.5/year)]. HC occurred in 63.0% during era 2 and in 29.4% during era 1 (P = 0.03). Era 2 donors had longer times for extubation-to-asystole (14.4 ± 4.7 m vs 9.3 ± 4.5 m, P = 0.001), ischemia (13.9 ± 5.9 m vs 9.7 ± 5.6 m, P = 0.03), and hypoxemia (16.0 ± 5.1 m vs 11.1 ± 6.7 m, P = 0.013) and a higher hypoxia score > 2.0 rate (73.1% vs 28.6%, P = 0.006). CONCLUSION: Easily measured donor indices, including a hypoxia score, provide an objective measure of DCD liver transplantation risk for recipient HC. Donor selection criteria influence HC rates. PMID:27022221

HEALTH STATUS OF RED-FOOTED BOOBIES ( SULA SULA) DETERMINED BY HEMATOLOGY, BIOCHEMISTRY, BLOOD GASES, AND PHYSICAL EXAMINATION.

PubMed

Lewbart, Gregory A; Ulloa, Catalina; Deresienski, Diane; Regalado, Cristina; Muñoz-Pérez, Juan-Pablo; Garcia, Juan; Hardesty, Britta Denise; Valle, Carlos A

2017-12-01

The red-footed booby ( Sula sula) is a widely distributed sulid native to the Galápagos archipelago. Hematology and blood chemistry parameters have been published for this species, but not from the San Cristóbal rookery. Analyses were run on blood samples drawn from 31 manually restrained red-footed boobies that were captured by hand from their nests at Punta Pitt on San Cristóbal Island. A portable blood analyzer (iSTAT) was used to obtain near immediate field results for pH, partial pressure of oxygen, partial pressure of carbon dioxide, bicarbonate, hematocrit, hemoglobin, sodium, potassium, ionized calcium, and glucose. Blood lactate was measured using a portable Lactate Plus™ analyzer. Average heart rate, respiratory rate, body weight, body temperature, and biochemistry and hematology parameters were comparable to those of healthy individuals of other sulids. The reported results provide baseline data that can be used for comparisons among populations and in detecting changes in health status among Galápagos red-footed boobies.

Evaluating appropriate red blood cell transfusions: a quality audit at 10 Ontario hospitals to determine the optimal measure for assessing appropriateness.

PubMed

Spradbrow, Jordan; Cohen, Robert; Lin, Yulia; Armali, Chantal; Collins, Allison; Cserti-Gazdewich, Christine; Lieberman, Lani; Pavenski, Katerina; Pendergrast, Jacob; Webert, Kathryn; Callum, Jeannie

2016-10-01

Evaluating the appropriateness of red blood cell (RBC) transfusion requires labor-intensive medical chart audits and expert adjudication. We sought to determine the appropriateness of RBC transfusions at 10 hospitals using retrospective chart review and to determine whether simple metrics (proportion of single-unit transfusions, RBCs/100 acute inpatient days, proportion of transfusions with pretransfusion hemoglobin <80 g/L or posttransfusion hemoglobin <90 g/L) could be used as surrogate markers of appropriateness by comparing their values with the results from the audit. An initial block of 30 RBC units was dually adjudicated for appropriateness followed by additional blocks of 10 units until the difference between the cumulative percentage of appropriate RBC units in the preceding block and final block was <3%. Pearson correlation tests were used to evaluate associations between the metrics and percentages of appropriate transfusions per hospital. Two-by-two tables were used to assess the utility of the metrics to classify transfusions for appropriateness. Of the 498 units audited, 78% were adjudicated as appropriate (κ = 0.9603), with significant variability between institutions (p < 0.0001). Fifty audits or less were required at nine of the institutions. The values of the metrics were not found to have significant correlations with appropriateness, and the metric that misclassified the smallest proportion of transfusions for appropriateness was pretransfusion hemoglobin <80 g/L, at 24%. Our findings suggest that a chart audit of 50 RBC transfusions with adjudication using robust criteria is the optimal means of evaluating RBC transfusion appropriateness at an institution for benchmarking and quality-improvement initiatives. © 2016 AABB.

Exposure from the Chernobyl accident had adverse effects on erythrocytes, leukocytes, and, platelets in children in the Narodichesky region, Ukraine: A 6-year follow-up study

PubMed Central

Stepanova, Eugenia; Karmaus, Wilfried; Naboka, Marina; Vdovenko, Vitaliy; Mousseau, Tim; Shestopalov, Viacheslav M; Vena, John; Svendsen, Erik; Underhill, Dwight; Pastides, Harris

2008-01-01

Background After the Chernobyl nuclear accident on April 26, 1986, all children in the contaminated territory of the Narodichesky region, Zhitomir Oblast, Ukraine, were obliged to participate in a yearly medical examination. We present the results from these examinations for the years 1993 to 1998. Since the hematopoietic system is an important target, we investigated the association between residential soil density of 137Caesium (137Cs) and hemoglobin concentration, and erythrocyte, platelet, and leukocyte counts in 1,251 children, using 4,989 repeated measurements taken from 1993 to 1998. Methods Soil contamination measurements from 38 settlements were used as exposures. Blood counts were conducted using the same auto-analyzer in all investigations for all years. We used linear mixed models to compensate for the repeated measurements of each child over the six year period. We estimated the adjusted means for all markers, controlling for potential confounders. Results Data show a statistically significant reduction in red and white blood cell counts, platelet counts and hemoglobin with increasing residential 137Cs soil contamination. Over the six-year observation period, hematologic markers did improve. In children with the higher exposure who were born before the accident, this improvement was more pronounced for platelet counts, and less for red blood cells and hemoglobin. There was no exposure×time interaction for white blood cell counts and not in 702 children who were born after the accident. The initial exposure gradient persisted in this sub-sample of children. Conclusion The study is the first longitudinal analysis from a large cohort of children after the Chernobyl accident. The findings suggest persistent adverse hematological effects associated with residential 137Cs exposure. PMID:18513393

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.

Establishment of reference intervals for complete blood count parameters during normal pregnancy in Beijing.

PubMed

Li, Aiwei; Yang, Shuo; Zhang, Jie; Qiao, Rui

2017-11-01

To observe the changes of complete blood count (CBC) parameters during pregnancy and establish appropriate reference intervals for healthy pregnant women. Healthy pregnant women took the blood tests at all trimesters. All blood samples were processed on Sysmex XE-2100. The following CBC parameters were analyzed: red blood cell count (RBC), hemoglobin (Hb), hematocrit (Hct), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), red blood cell distribution width (RDW), platelet count (PLT), mean platelet volume (MPV), platelet distribution width (PDW), white blood cell count (WBC), and leukocyte differential count. Reference intervals were established using the 2.5th and 97.5th percentile of the distribution. Complete blood count parameters showed dynamic changes during trimesters. RBC, Hb, Hct declined at trimester 1, reaching their lowest point at trimester 2, and began to rise again at trimester 3. WBC, neutrophil count (Neut), monocyte count (MONO), RDW, and PDW went up from trimester 1 to trimester 3. On the contrary, MCHC, lymphocyte count (LYMPH), PLT, and MPV gradually descended during pregnancy. There were statistical significances in all CBC parameters between pregnant women and normal women, regardless of the trimesters (P<.001). The median obtained were (normal vs pregnancy) as follows: RBC 4.50 vs 3.94×10 12 /L, Hb 137 vs 120 g/L, WBC 5.71 vs 9.06×10 9 /L, LYMPH% 32.2 vs 18.0, Neut% 58.7 vs 75.0, and PLT 251 vs 202×10 9 /L. The changes of CBC parameters during pregnancy are described, and reference intervals for Beijing pregnant women are demonstrated in this study. © 2017 Wiley Periodicals, Inc.

Measurement of total hemoglobin reduces red cell transfusion in hospitalized patients undergoing cardiac surgery: a retrospective database analysis.

PubMed

Craver, Christopher; Belk, Kathy W; Myers, Gerard J

2018-01-01

Historically, perioperative hemoglobin monitoring has relied on calculated saturation, using blood gas devices that measure plasma hematocrit (Hct). Co-oximetry, which measures total hemoglobin (tHb), yields a more comprehensive assessment of hemodilution. The purpose of this study was to examine the association of tHb measurement by co-oximetry and Hct, using conductivity with red blood cell (RBC) transfusion, length of stay (LOS) and inpatient costs in patients having major cardiac surgery. A retrospective study was conducted on patients who underwent coronary artery bypass graft (CABG) and/or valve replacement (VR) procedures from January 2014 to June 2016, using MedAssets discharge data. The patient population was sub-divided by the measurement modality (tHb and Hct), using detailed billing records and Current Procedural Terminology coding. Cost was calculated using hospital-specific cost-to-charge ratios. Multivariable logistic regression was performed to identify significant drivers of RBC transfusion and resource utilization. The study population included 18,169 cardiovascular surgery patients. Hct-monitored patients accounted for 66% of the population and were more likely to have dual CABG and VR procedures (10.4% vs 8.9%, p=0.0069). After controlling for patient and hospital characteristics, as well as patient comorbidities, Hct-monitored patients had significantly higher RBC transfusion risk (OR=1.26, CI 1.15-1.38, p<0.0001), longer LOS (IRR=1.08, p<0.0001) and higher costs (IRR=1.15, p<0.0001) than tHb-monitored patients. RBC transfusions were a significant driver of LOS (IRR=1.25, p<0.0001) and cost (IRR=1.22, p<0.0001). tHb monitoring during cardiovascular surgery could offer a significant reduction in RBC transfusion, length of stay and hospital cost compared to Hct monitoring.

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

Phenotypic plasticity in blood–oxygen transport in highland and lowland deer mice

PubMed Central

Tufts, Danielle M.; Revsbech, Inge G.; Cheviron, Zachary A.; Weber, Roy E.; Fago, Angela; Storz, Jay F.

2013-01-01

SUMMARY In vertebrates living at high altitude, arterial hypoxemia may be ameliorated by reversible changes in the oxygen-carrying capacity of the blood (regulated by erythropoiesis) and/or changes in blood–oxygen affinity (regulated by allosteric effectors of hemoglobin function). These hematological traits often differ between taxa that are native to different elevational zones, but it is often unknown whether the observed physiological differences reflect fixed, genetically based differences or environmentally induced acclimatization responses (phenotypic plasticity). Here, we report measurements of hematological traits related to blood–O2 transport in populations of deer mice (Peromyscus maniculatus) that are native to high- and low-altitude environments. We conducted a common-garden breeding experiment to assess whether altitude-related physiological differences were attributable to developmental plasticity and/or physiological plasticity during adulthood. Under conditions prevailing in their native habitats, high-altitude deer mice from the Rocky Mountains exhibited a number of pronounced hematological differences relative to low-altitude conspecifics from the Great Plains: higher hemoglobin concentrations, higher hematocrits, higher erythrocytic concentrations of 2,3-diphosphoglycerate (an allosteric regulator of hemoglobin–oxygen affinity), lower mean corpuscular hemoglobin concentrations and smaller red blood cells. However, these differences disappeared after 6 weeks of acclimation to normoxia at low altitude. The measured traits were also indistinguishable between the F1 progeny of highland and lowland mice, indicating that there were no persistent differences in phenotype that could be attributed to developmental plasticity. These results indicate that the naturally occurring hematological differences between highland and lowland mice are environmentally induced and are largely attributable to physiological plasticity during adulthood. PMID:23239893

CLINICAL APPLICATION OF RECOMBINANT ERYTHROPOIETIN IN BETA-THALASSAEMIA INTERMEDIA.

PubMed

Asadov, Ch; Alimirzoyeva, Z; Hasanova, M; Mammadova, T; Shirinova, A

2016-06-01

Research objective is to study the efficacy of recombinant erythropoietin (epoetin alfa) as alternative method of treatment beta-thalassemia intermedia. Study involved 58 patients with beta-thalassemia intermedia (23 women and 35 men). In all observed patients was defined levels of hemoglobin (Hb), red blood cells (RBC), erythrocyte indexes (MCV, MCH, MCHC), hemoglobin fractions (HbA, HbA2, HbF), serum ferritin, serum erythropoietin before and after administrated rEPO. All patients received rEPO during 6 month at the dose - 10000 IU subcutaneously. The majority of patients - 39 (67%) had a good response to rEPO (increase in hemoglobin level more than 20 g/l); 16 patients (28%) had a mean response (increase in Hb 10 - 20 g/l); in 3 (5%) patients occurred poor response to rEPO therapy (increase in Hb <10 g/l). After rEPO treatment of beta-thalassemia intermedia patients there was a statistically significant change in the number of RBC, levels of HbF and sEPO. The evaluation of interdependence between the indices of the baseline sEPO and increased Hb values in patients after rEPO treatment revealed the presence of the reverse direct relationship (r=-0.67). Based on the results, it can be concluded that the use of rEPO in complex therapy of beta-thalassemia intermedia leads to increased levels of Hb and consequently reducing the need for blood transfusions, and accordingly expected to prevent severe complications of blood transfusion (alloimmunization, hypersplenism, iron overload, contamination transmissible infections) facilitating normal growth and development, and a better quality of life.

Multispectral imaging of absorption and scattering properties of in vivo exposed rat brain using a digital red-green-blue camera.

PubMed

Yoshida, Keiichiro; Nishidate, Izumi; Ishizuka, Tomohiro; Kawauchi, Satoko; Sato, Shunichi; Sato, Manabu

2015-05-01

In order to estimate multispectral images of the absorption and scattering properties in the cerebral cortex of in vivo rat brain, we investigated spectral reflectance images estimated by the Wiener estimation method using a digital RGB camera. A Monte Carlo simulation-based multiple regression analysis for the corresponding spectral absorbance images at nine wavelengths (500, 520, 540, 560, 570, 580, 600, 730, and 760 nm) was then used to specify the absorption and scattering parameters of brain tissue. In this analysis, the concentrations of oxygenated hemoglobin and that of deoxygenated hemoglobin were estimated as the absorption parameters, whereas the coefficient a and the exponent b of the reduced scattering coefficient spectrum approximated by a power law function were estimated as the scattering parameters. The spectra of absorption and reduced scattering coefficients were reconstructed from the absorption and scattering parameters, and the spectral images of absorption and reduced scattering coefficients were then estimated. In order to confirm the feasibility of this method, we performed in vivo experiments on exposed rat brain. The estimated images of the absorption coefficients were dominated by the spectral characteristics of hemoglobin. The estimated spectral images of the reduced scattering coefficients had a broad scattering spectrum, exhibiting a larger magnitude at shorter wavelengths, corresponding to the typical spectrum of brain tissue published in the literature. The changes in the estimated absorption and scattering parameters during normoxia, hyperoxia, and anoxia indicate the potential applicability of the method by which to evaluate the pathophysiological conditions of in vivo brain due to the loss of tissue viability.

Anemia prevalence and risk factors in pregnant women in an urban area of Pakistan

PubMed Central

Baig-Ansari, Naila; Badruddin, Salma Halai; Karmaliani, Rozina; Harris, Hillary; Jehan, Imtiaz; Pasha, Omrana; Moss, Nancy; McClure, Elizabeth M.; Goldenberg, Robert L.

2014-01-01

Background. Anemia affects almost two-thirds of pregnant women in developing countries and contributes to maternal morbidity and mortality and to low birthweight. Objective. To determine the prevalence of anemia and the dietary and socioeconomic factors associated with anemia in pregnant women living in an urban community setting in Hyderabad, Pakistan. Methods. This was a prospective, observational study of 1,369 pregnant women enrolled at 20 to 26 weeks of gestation and followed to 6 weeks postpartum. A blood sample was obtained at enrollment to determine hemoglobin levels. Information on nutritional knowledge, attitudes, and practice and dietary history regarding usual food intake before and during pregnancy were obtained by trained interviewers within 1 week of enrollment. Results. The prevalence of anemia (defined by the World Health Organization as hemoglobin < 11.0 g/dL) in these subjects was 90.5%; of these, 75.0% had mild anemia (hemoglobin from 9.0 to 10.9 g/dL) and 14.8% had moderate anemia (hemoglobin from 7.0 to 8.9 g/dL). Only 0.7% were severely anemic (hemoglobin < 7.0 g/dL). Nonanemic women were significantly taller, weighed more, and had a higher body mass index. Multivariate analysis after adjustment for education, pregnancy history, iron supplementation, and height showed that drinking more than three cups of tea per day before pregnancy (adjusted prevalence odds ratio [aPOR], 3.2; 95% confidence interval [CI], 1.3 to 8.0), consumption of clay or dirt during pregnancy (aPOR, 3.7; 95% CI, 1.1 to 12.3), and never consuming eggs or consuming eggs less than twice a week during pregnancy (aPOR, 1.7; 95% CI, 1.1 to 2.5) were significantly associated with anemia. Consumption of red meat less than twice a week prior to pregnancy was marginally associated with anemia (aPOR, 1.2; 95% CI, 0.8 to 1.8) but was significantly associated with lower mean hemoglobin concentrations (9.9 vs. 10.0 g/dL, p = .05) during the study period. A subanalysis excluding women with mild anemia found similar associations to those of the main model, albeit even stronger. Conclusions. A high percentage of women at 20 to 26 weeks of pregnancy had mild to moderate anemia. Pica, tea consumption, and low intake of eggs and red meat were associated with anemia. Women of childbearing age should be provided nutritional education regarding food sources of iron, especially prior to becoming pregnant, and taught how food choices can either enhance or interfere with iron absorption. PMID:18693477

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

NASA Astrophysics Data System (ADS)

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

2018-02-01

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

Hematological findings in neotropical fish Hoplias malabaricus exposed to subchronic and dietary doses of methylmercury, inorganic lead, and tributyltin chloride

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

Oliveira Ribeiro, C.A.; Filipak Neto, F.; Mela, M.

2006-05-15

Hematological indices are gaining general acceptance as valuable tools in monitoring various aspects the health of fish exposed to contaminants. In this work some effects of methyl mercury (MeHg), inorganic lead (Pb{sup 2+}), and tributyltin (TBT) in a tropical fish species were evaluated by hematological methods after a trophic exposition at a subchronic level. Forty-two mature individuals of the freshwater top predator fish Hoplias malabaricus were exposed to trophic doses (each 5 days) of MeHg (0.075 {mu}g g{sup -1}), Pb{sup 2+} (21 {mu}g g{sup -1}), and TBT (0.3 {mu}g g{sup -1}) using young fish Astyanax sp. as prey vehicle. Aftermore » 14 successive doses over 70 days, blood was sampled from exposed and control groups to evaluate hematological effects of metals on erythrocytes, total leukocytes and differential leukocytes counts, hematocrit, hemoglobin concentration, and red blood cell indices mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC). Transmission electron microscopy and image analysis of erythrocytes were also used to investigate some morphometric parameters. Results show no significant effects in MCH and MCHC for all tested metals, but differences were found in erythrocytes, hemoglobin, hematocrit, MCV, and white blood cells counts. The number of leukocytes was increased in the presence of MeHg, suggesting effects on the immune system. Also the MCV increased in individuals exposed to MeHg. No ultrastructural damages were observed in red blood cells but the image analysis using light microscopy revealed differences in area, elongation, and roundness of erythrocytes from individuals exposed to Pb{sup 2+} and TBT but not in the group exposed to MeHg. The present work shows that changes in hematological and blood indices could highlight some barely detectable metal effects in fish after laboratory exposure to contaminated food, but their application in field biomonitoring using H. malabaricus will need more detailed studies and a careful consideration of environmental parameters.« less

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.).

[Effects of tranexamic acid combined with temporary drain clamping on postoperative blood loss in total knee arthroplasty].

PubMed

Dong, Yi-Long; Qian, Yue-Nan; Zhong, Xi-Qiang; Shen, Guang-Jie; Cai, Chun-Yuan

2017-04-25

To evaluate the efficacy and safety of one dose tranexamic acid combined with temporary drain lamping in primary unilateral total knee arthroplasty. Total 160 patients undergoing unilateral primary total knee arthroplasty between January 2012 and December 2013 were randomly divided into four groups(40 cases in each group):group A (the drain was clamped for 2 hours after the operation and the patients received 20 ml physiological saline), group B(the drain was clamped for 2 hours after the operation and the patients received 10 ml tranexamic acid and 10 ml physiological saline), group C (the drain was clamped for 4 hours after the operation and the patients received 20 ml physiological saline) and group D(the drain was clamped for 4 hours after the operation and the patients received 10 ml tranexamic acid and 10 ml physiological saline). The postoperative hemoglobin level, maximum hemoglobin loss, wound drainage, blood loss, the volume of blood transfusion, the number of patients inquiring blood transfusion, venous thrombo embolism rate, and ecchymosis rate were recorded and compared among the four groups. There was no incision infection, severe hypoxia, and symptomatic pulmonary embolism in these groups. There were significant differences in hemoglobin content one day after operation in each group( F =12.26, P =0.000), in the hemoglobin content 7 days after operation in each group( F =20.74, P =0.000), in postoperative drainage in each group( F =38.71, P =0.000);in the amount of invisible red blood cell loss in each group( F =83.41, P =0.000), and in total red blood cell loss in each group( F =102.68, P =0.000). Color Doppler ultrasound examination found that the total incidence of VTE was 3%(5/160) and there were no significant differences in each group( P =0.892). There were no significant differences in postoperative subcutaneous ecchymosis area>1% incidence( P =0.143). Topical tranexami acid treatment combined with temporary clamping of drain for 4 hours could reduce postoperative blood loss, blood transfusion, and ecchymosis rate without increasing the risk of thromboembolic event after total knee arthroplasty.

A comparison of blood nitric oxide metabolites and hemoglobin functional properties among diving mammals.

PubMed

Fago, Angela; Parraga, Daniel Garcia; Petersen, Elin E; Kristensen, Niels; Giouri, Lea; Jensen, Frank B

2017-03-01

The ability of marine mammals to hunt prey at depth is known to rely on enhanced oxygen stores and on selective distribution of blood flow, but the molecular mechanisms regulating blood flow and oxygen transport remain unresolved. To investigate the molecular mechanisms that may be important in regulating blood flow, we measured concentration of nitrite and S-nitrosothiols (SNO), two metabolites of the vasodilator nitric oxide (NO), in the blood of 5 species of marine mammals differing in their dive duration: bottlenose dolphin, South American sea lion, harbor seal, walrus and beluga whale. We also examined oxygen affinity, sensitivity to 2,3-diphosphoglycerate (DPG) and nitrite reductase activity of the hemoglobin (Hb) to search for possible adaptive variations in these functional properties. We found levels of plasma and red blood cells nitrite similar to those reported for terrestrial mammals, but unusually high concentrations of red blood cell SNO in bottlenose dolphin, walrus and beluga whale, suggesting enhanced SNO-dependent signaling in these species. Purified Hbs showed similar functional properties in terms of oxygen affinity and sensitivity to DPG, indicating that reported large variations in blood oxygen affinity among diving mammals likely derive from phenotypic variations in red blood cell DPG levels. The nitrite reductase activities of the Hbs were overall slightly higher than that of human Hb, with the Hb of beluga whale, capable of longest dives, having the highest activity. Taken together, these results underscore adaptive variations in circulatory NO metabolism in diving mammals but not in the oxygenation properties of the Hb. Copyright © 2016 Elsevier Inc. All rights reserved.

Comparative study of the effect of BPA and its selected analogues on hemoglobin oxidation, morphological alterations and hemolytic changes in human erythrocytes.

PubMed

Maćczak, Aneta; Bukowska, Bożena; Michałowicz, Jaromir

2015-01-01

Bisphenol A (BPA) has been shown to provoke many deleterious impacts on human health, and thus it is now successively substituted by BPA analogues, whose effects have been poorly investigated. Up to now, only one study has been realized to assess the effect of BPA on human erythrocytes, which showed its significant hemolytic and oxidative potential. Moreover, no study has been conducted to evaluate the effect of BPA analogues on red blood cells. The purpose of the present study was to compare the impact of BPA and its selected analogues such as bisphenol F (BPF), bisphenol S (BPS) and bisphenol AF (BPAF) on hemolytic and morphological changes and hemoglobin oxidation (methemoglobin formation) of human erythrocytes. The erythrocytes were incubated with different bisphenols concentrations ranging from 0.5 to 500μg/ml for 1, 4 and 24h. The compounds examined caused hemolysis in human erythrocytes with BPAF exhibiting the strongest effect. All bisphenols examined caused methemoglobin formation with BPA inducing the strongest oxidative potential. Flow cytometry analysis showed that all bisphenols (excluding BPS) induced significant changes in erythrocytes size. Changes in red blood cells shape were conducted using phase contrast microscopy. It was noticed that BPA and BPAF induced echinocytosis, BPF caused stomatocytosis, while BPS did not provoke significant changes in shape of red blood cells. Generally, the results showed that BPS, which is the main substituent of bisphenol A in polymers and thermal paper production, exhibited significantly lower disturbance of erythrocyte functions than BPA. Copyright © 2015 Elsevier Inc. All rights reserved.

Mechanism of transport and distribution of organic solvents in blood

NASA Technical Reports Server (NTRS)

Lam, C. W.; Galen, T. J.; Boyd, J. F.; Pierson, D. L.

1990-01-01

Little is known about the mechanism of transport and distribution of volatile organic compounds in blood. Studies were conducted on five typical organic solvents to investigate how these compounds are transported and distributed in blood. Groups of four to five rats were exposed for 2 hr to 500 ppm of n-hexane, toluene, chloroform, methyl isobutyl ketone (MIBK), or diethyl ether vapor; 94, 66, 90, 51, or 49%, respectively, of these solvents in the blood were found in the red blood cells (RBCs). Very similar results were obtained in vitro when aqueous solutions of these solvents were added to rat blood. In vitro studies were also conducted on human blood with these solvents; 66, 43, 65, 49, or 46%, respectively, of the added solvent was taken up by the RBCs. These results indicate that RBCs from humans and rats exhibited substantial differences in affinity for the three more hydrophobic solvents studied. When solutions of these solvents were added to human plasma and RBC samples, large fractions (51-96%) of the solvents were recovered from ammonium sulfate-precipitated plasma proteins and hemoglobin. Smaller fractions were recovered from plasma water and red cell water. Less than 10% of each of the added solvents in RBC samples was found in the red cell membrane ghosts. These results indicate that RBCs play an important role in the uptake and transport of these solvents. Proteins, chiefly hemoglobin, are the major carriers of these compounds in blood. It can be inferred from the results of the present study that volatile lipophilic organic solvents are probably taken up by the hydrophobic sites of blood proteins.

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

Drugs for preventing red blood cell dehydration in people with sickle cell disease.

PubMed

Nagalla, Srikanth; Ballas, Samir K

2012-07-11

Sickle cell disease is an inherited disorder of hemoglobin, resulting in abnormal red blood cells. These are rigid and may block blood vessels leading to acute painful crises and other complications. Recent research has focused on therapies to rehydrate the sickled cells by reducing the loss of water and ions from them. Little is known about the effectiveness and safety of such drugs. To assess the relative risks and benefits of drugs to rehydrate sickled red blood cells. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register.Last search of the Group's Trials Register: 25 October 2011. Randomized or quasi-randomized controlled trials of drugs to rehydrate sickled red blood cells compared to placebo or an alternative treatment. Both authors independently selected studies for inclusion, assessed study quality and extracted data. Of the 51 studies identified, three met the inclusion criteria. The first study tested the effectiveness of zinc sulphate to prevent sickle cell-related crises in a total of 145 participants and showed a significant reduction in painful crises over one and a half years, mean difference -2.83 (95% confidence interval -3.51 to -2.15). However, analysis was restricted due to limited statistical data. Changes to red cell parameters and blood counts were inconsistent. No serious adverse events were noted in the study.The second study was a Phase II dose-finding study of senicapoc (a Gardos channel blocker) compared to placebo. Compared to the placebo group the high dose senicapoc showed significant improvement in change in hemoglobin level, number and proportion of dense red blood cells, red blood cell count and indices and hematocrit. The results with low-dose senicapoc were similar to the high-dose senicapoc group but of lesser magnitude. There was no difference in the frequency of painful crises between the three groups. A subsequent Phase III study of senicapoc was terminated early since there was no difference observed between the treatment and control groups in the primary end point of painful crises. While the results of zinc for reducing sickle-related crises are encouraging, larger and longer-term multicenter studies are needed to evaluate the effectiveness of this therapy for people with sickle cell disease.While the Phase II and the prematurely terminated phase III studies of senicapoc showed that the drug improved red cell survival (depending on dose), this did not lead to fewer painful crises.

Pathophysiology and Clinical Manifestations of the β-Thalassemias

PubMed Central

Nienhuis, Arthur W.; Nathan, David G.

2012-01-01

The β-thalassemia syndromes reflect deficient or absent β-globin synthesis usually owing to a mutation in the β-globin locus. The relative excess of α-globin results in the formation of insoluble aggregates leading to ineffective erythropoiesis and shortened red cell survival. A relatively high capacity for fetal hemoglobin synthesis is a major genetic modifier of disease severity, with polymorphisms in other genes also having a significant role. Iron overload secondary to enhanced absorption and red cell transfusions causes an increase in liver iron and in various other tissues, leading to endocrine and cardiac dysfunction. Modern chelation regimens are effective in removing iron and preserving or restoring organ function. PMID:23209183

Rapid identification of iron deficiency in blood donors with red cell indexes provided by Advia 120.

PubMed

Radtke, Hartmut; Meyer, Tina; Kalus, Ulrich; Röcker, Lothar; Salama, Abdulgabar; Kiesewetter, Holger; Latza, Reinhard

2005-01-01

A new generation of automated hematology analyzers allows the rapid determination of various red cell (RBC) indexes, including the percentage of hypochromic mature RBCs (HYPOm) and the hemoglobin (Hb) content of reticulocytes (CHr). These indexes have not yet been validated as measures for the detection of iron deficiency in blood donors. Iron status was evaluated in a total of 1142 unselected prospective blood donors based on measurement of serum ferritin, soluble transferrin receptor, and Hb compared to RBC indexes provided by an automated hematology analyzer (Advia 120, Bayer HealthCare) including HYPOm and CHr. Assuming that the most precise measure for body iron storage is related to the logarithm of the ratio of soluble transferrin receptor to ferritin, the sensitivity of ferritin for the diagnosis of iron depletion was 89 percent compared to 57 percent for HYPOm and CHr, respectively, to 69 percent for the combination of both RBC indexes, and to 26 percent for Hb concentration. The RBC indexes HYPOm und CHr are significantly better screening measures for identification of iron depletion in blood donors than Hb.

Continuous optical measurement system of hemolysis during a photosensitization reaction using absorption spectrum

NASA Astrophysics Data System (ADS)

Hamada, R.; Ogawa, E.; Arai, T.

2018-02-01

To investigate hemolysis phenomena during a photosensitization reaction with the reaction condition continuously and simultaneously for a safety assessment of hemolysis side effect, we constructed an optical system to measure blood sample absorption spectrum during the reaction. Hemolysis degree might be under estimated in general evaluation methods because there is a constant oxygen pressure assumption in spite of oxygen depression take place. By investigating hemoglobin oxidation and oxygen desorption dynamics obtained from the contribution of the visible absorption spectrum and multiple regression analysis, both the hemolysis phenomena and its oxygen environment might be obtained with time. A 664 nm wavelength laser beam for the reaction excitation and 475-650 nm light beam for measuring the absorbance spectrum were arranged perpendicularly crossing. A quartz glass cuvette with 1×10 mm in dimensions for the spectrum measurement was located at this crossing point. A red blood cells suspension medium was arranged with low hematocrit containing 30 μg/ml talaporfin sodium. This medium was irradiated up to 40 J/cm2 . The met-hemoglobin, oxygenatedhemoglobin, and deoxygenated-hemoglobin concentrations were calculated by a multiple regression analysis from the measured spectra. We confirmed the met-hemoglobin concentration increased and oxygen saturation decreased with the irradiation time, which seems to indicate the hemolysis progression and oxygen consumption, respectively. By using our measuring system, the hemolysis progression seems to be obtained with oxygen environment information.

A Rare Non-Hemolytic Case of Idiopathic Cold Agglutinin Disease.

PubMed

Erkus, Edip; Kocak, Mehmet Z; Aktas, Gulali; Ozen, Mehmet; Atak, Burcin M; Duman, Tuba T; Tekce, Buket K; Savli, Haluk

2018-06-01

Cold agglutinin disease is a very rare condition associated with agglutination of erythrocytes in cold environment usually due to IgM type antibodies. Other than hemolytic anemias, it may interfere with routine hemogram tests due to miscalculation of red blood cell count (RBC) and other hemogram parameters calculated with involvement of RBC. Awareness of the condition is important to overcome laboratory errors. We studied a peripheral blood smear and repeated the hemogram test at 37°C to establish the diagnosis of cold agglutinin disease. Initial hemogram test results of the fifty-eight year-old man was as follows: RBC: 1.34 M/µL, hemoglobin (Hb): 12.4 g/dL, hematocrit (Htc): 11.8%, mean corpuscular hemoglobin (MCH): 92.4 pg, and mean corpuscular hemoglobin concentration (MCHC): 105 gr/dL. Despite the standard indirect Coombs test being negative, repeated tests at room temperature was 4+. We suspected cold agglutinin disease and repeated the hemogram test using the Bain-Marie method at 37°C and the test results showed RBC: 3.4 M/µL, hemoglobin: 12.6 g/dL, hematocrit: 30.2%, MCH: 31.7 pg, and MCHC: 41.8 g/dL. Inappropriate hemogram results may be a sign of underlying cold agglutinin disease. Hemolytic anemia not always accompanies the disease; however, cold exposure may trigger erythrocyte agglutination in vitro and may cause erratic laboratory results.

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.

Red maple (Acer rubrum) leaf toxicosis in horses: a retrospective study of 32 cases.

PubMed

Alward, Ashley; Corriher, Candice A; Barton, Michelle H; Sellon, Debra C; Blikslager, Anthony T; Jones, Samuel L

2006-01-01

Ingestion of wilted red maple leaves by horses can result in severe hemolytic anemia and methemoglobinemia. Little is known about what factors influence the outcome of red maple leaf toxicosis in horses. Our hypothesis was that physical examination findings, clinicopathologic variables or therapeutic modalities may predict outcome in horses with red maple leaf toxicity. Horses with red maple leaf toxicosis presented to referral hospitals in the southeast region of the United States. A multi-institutional retrospective study was designed to identify factors that predict mortality in horses with red maple toxicosis. Thirty-two horses with red maple toxicosis were identified, 19 of which died. Twenty-nine horses presented with anemia and 24 had clinicopathologic evidence of systemic inflammation. Renal insufficiency was identified in 12/30 (41%) horses. Laminitis (9/28) and colic (13/30) also were identified in horses with red maple toxicosis, but development of these 2 conditions did not have a negative effect on short-term survival. Horses with red maple toxicosis that survived to discharge were likely to have developed pyrexia during hospitalization (P = .030). Horses that were treated with a corticosteroid had a significantly increased likelihood of death (P = .045). There was no significant relationship between initial serum hemoglobin concentration, methemoglobin concentration, or percentage methemoglobin and mortality in this horse series. This study suggests that information obtained on initial examination cannot be used to accurately predict survival in horses with red maple toxicosis, but horses that receive corticosteroids are unlikely to survive.

Burn Injuries in Children and the Use of Biological Dressings

DTIC Science & Technology

2013-08-01

in, any commercial or- ganizations pertaining to this educational activity. The opinions or assertions contained herein are the private views of the...and mechanical integrity of the skin.6 Blood vessels run within the dermis and extend into the dermal papillae, providing nutrition . Beneath the dermis...confined places where oxygen is replaced by dangerous gases. Carbon monoxide binds the hemoglobin molecule in red blood cells more strongly than does

Abstracts of Papers Presented at the Annual Meeting of the Society of General Physiologists Held at Woods Hole, Massachusetts on 10-13 September 1992.

DTIC Science & Technology

1992-09-13

Qualitative Alteration of K-Cl Cotransport in Red Blood Cells with Hemoglobin S NORMA C. ADRAGNA and PETER K. LAUF, Departments of Pharmacology & Toxicology and...Adair, B. D.. 2 Brant. S. R.. 107. 122, 138 Adragna . N. C.. 139 Breituieser. (G. E., 150 Agre, P.. 127 Brot-Liroche. E., 147 Aitnizo. M.. 43 Browning, K

The Molecular Epidemiology of Malaria in Western Kenya

DTIC Science & Technology

2002-09-01

earliest identified) genetic factors are the inherited disorders of hemoglobin (sickle cell and thalassemia ). Individuals that are homozygous for the HbS...probably due to impaired entry into, and growth of parasites in, affected erythrocytes (8). The mechanism of protection of α and β thalassemia ...observed among young children with α− thalassemia (9). 4 The authors have proposed that more frequent infections of immature red blood cells might

Sickle cell disease biochip: a functional red blood cell adhesion assay for monitoring sickle cell disease

PubMed Central

ALAPAN, YUNUS; KIM, CEONNE; ADHIKARI, ANIMA; GRAY, KAYLA E.; GURKAN-CAVUSOGLU, EVREN; LITTLE, JANE A.; GURKAN, UMUT A.

2016-01-01

Sickle cell disease (SCD) afflicts millions of people worldwide and is associated with considerable morbidity and mortality. Chronic and acute vaso-occlusion are the clinical hallmarks of SCD and can result in pain crisis, widespread organ damage, and early movtality. Even though the molecular underpinnings of SCD were identified more than 60 years ago, there are no molecular or biophysical markers of disease severity that are feasibly measured in the clinic. Abnormal cellular adhesion to vascular endothelium is at the root of vaso-occlusion. However, cellular adhesion is not currently evaluated clinically. Here, we present a clinically applicable microfluidic device (SCD biochip) that allows serial quantitative evaluation of red blood cell (RBC) adhesion to endothelium-associated protein-immobilized microchannels, in a closed and preprocessing-free system. With the SCD biochip, we have analyzed blood samples from more than 100 subjects and have shown associations between the measured RBC adhesion to endothelium-associated proteins (fibronectin and laminin) and individual RBC characteristics, including hemoglobin content, fetal hemoglobin concentration, plasma lactate dehydrogenase level, and reticulocyte count. The SCD biochip is a functional adhesion assay, reflecting quantitative evaluation of RBC adhesion, which could be used at baseline, during crises, relative to various long-term complications, and before and after therapeutic interventions. PMID:27063958

Ameliorative Effects of Operculina turpethum and its Isolated Stigma-5,22dien-3-o-β-D-glucopyranoside on the Hematological Parameters of Male Mice Exposed to N-Nitrosodimethylamine, a Potent Carcinogen

PubMed Central

Sharma, Veena; Singh, Manu

2014-01-01

Objectives: Enormous propensity of plants to synthesize a variety of structurally diverse bioactive compounds, has made the plant kingdom a potential source of chemical constituents with various therapeutic values, including antitumor and cytotoxic activities. Blood is a good indicator to determine the physiological and pathological status of man and animal. The objective of the present study is to determine the effect of Operculina turpethum root extract and its isolated glycoside treatment on the hematological parameters in the mice with N-Nitrosodimethylamine (NDMA) induced cancer. Materials and Methods: The body weights of the animals were recorded before and after the experiment. Non-coagulated blood was tested for total erythrocyte count, total leukocyte count, hemoglobin, differential leukocyte count (DLC) and for other blood indices. Results: A significant (P < 0.01), (P < 0.001) recovery of the red blood cell and white blood cell counts, packed cell volume and hemoglobin content in the host after 21 day treatment was shown. Conclusion: These results show that the extract of Operculina turpethum is relatively safe following oral administration and have possible stimulatory effect on red blood cell production and there was dose dependent therapeutic effect. PMID:24748732

The Effect of Size of Red Cells on the Kinetics of Their Oxygen Uptake

PubMed Central

Holland, R. A. B.; Forster, R. E.

1966-01-01

Using a double-beam stopped-flow apparatus estimations were made of the velocity constant for the initial uptake of oxygen by fully reduced erythrocytes (k'c). Mammalian cells were studied with volumes varying from 20 µ3 (goat) to 90 µ3 (man), as were bullfrog cells (680 µ3). Measurements were made under physiological conditions of pH, P CO2, and temperature. In man k'c was 80 mM -1 sec-1 and in other species smaller cells generally had a greater value for k'c than did the larger cells. In the goat it was 1.8 times as great as the human value; in the bullfrog it was only one-fifth as great. These differences could not be accounted for by interspecific differences in hemoglobin kinetics. The differences probably represent a true effect of size conferring some biological advantage on the species with the smaller cells. The cell membrane offered resistance to oxygen passage. Using the usual red cell model of an infinite sheet of reduced hemoglobin, membrane permeability appeared to differ among mammals. If, as is likely, the effective cell halfthickness differs among mammals, actual membrane permeability differences may be less. A method for measurement of oxygen saturation of dilute cell suspensions is also described. PMID:5943611

Quality of Evidence-Based Guidelines for Transfusion of Red Blood Cells and Plasma: A Systematic Review.

PubMed

Pavenski, Katerina; Stanworth, Simon; Fung, Mark; Wood, Erica M; Pink, Joanne; Murphy, Michael F; Hume, Heather; Nahirniak, Susan; Webert, Kathryn E; Tanael, Susano; Landry, Denise; Shehata, Nadine

2018-06-01

Many transfusion guidelines are available, but little appraisal of their quality has been undertaken. The quality of guidelines may potentially influence adoption. Our aim was to determine the quality of evidence-based transfusion guidelines (EBG) for red cells and plasma, using the Appraisal of Guidelines for Research and Evaluation (AGREE II) instrument, and assess duplication and consistency of recommendations. MEDLINE and EMBASE were systematically searched for EBG from 2005 to June 3, 2016. Citations were reviewed for inclusion in duplicate. A guideline was included if it had a specified clinical question, described a systematic search strategy, included critical appraisal of the literature and a description of how recommendations were developed. Four to six physicians used AGREE II to appraise each guideline. Median and scaled scores were calculated, with each item scored on a scale of one to seven, seven representing the highest score. Of 6174 citations, 30 guidelines met inclusion criteria. Twenty six guidelines had recommendations for red cells and 18 included recommendations for plasma use. The median score, the scaled score and the interquartile range of the scaled score were: scope and purpose: median score 5, scaled score 60%, IQR (49-74%); stakeholder involvement 4, 43%, (33-49%); rigor of development 4, 41%, (19-59%); clarity of presentation 5, 69%, (52-81%); applicability 1, 16%, (9-23%); editorial independence 3, 43%, (20-58%). Sixteen guidelines were evaluated to have a scaled domain score of 50% or less. Variations in recommendations were found for the use of hemoglobin triggers for red cell transfusion in patients with acute coronary syndromes and for plasma use for patients with bleeding. Our findings document, limited rigor in guideline development and duplication and inconsistencies in recommendations for the same topic. The process of developing guidelines for red cells and plasma transfusion can be enhanced to improve implementation. Copyright © 2018 Elsevier Inc. All rights reserved.

PLASMA AND RED CELL RADIOIRON FOLLOWING INTRAVENOUS INJECTION

PubMed Central

Yuile, C. L.; Bly, C. G.; Stewart, W. B.; Izzo, A. J.; Wells, J. C.; Whipple, G. H.

1949-01-01

Sterile inflammation induced by repeated subcutaneous injections of turpentine in non-anemic, non-iron—deficient dogs, leads to a fall in plasma iron concentration, the development of a moderate anemia, and a marked delay in the uptake by the red blood cells of intravenous radioiron. Similar periods of inflammation in anemic, iron-deficient dogs on a diet low in iron cause no increase in the degree of anemia and no inhibition of red blood cell uptake of intravenous radioiron. Radioiron appears only in traces in abscess exudates. Intravenous iron disappearance curves following a single injection are uninfluenced by sterile inflammation in either anemic or non-anemic dogs. The impairment of hemoglobin synthesis caused by inflammation is at most a relative matter, since the anemia that develops is seldom severe or progressive, and since the inhibition can be overcome if the marrow is sufficiently stimulated by the demands of a severe continuing anemia. PMID:18140660

Multi-omics Evidence for Inheritance of Energy Pathways in Red Blood Cells.

PubMed

Weisenhorn, Erin M M; van T Erve, Thomas J; Riley, Nicholas M; Hess, John R; Raife, Thomas J; Coon, Joshua J

2016-12-01

Each year over 90 million units of blood are transfused worldwide. Our dependence on this blood supply mandates optimized blood management and storage. During storage, red blood cells undergo degenerative processes resulting in altered metabolic characteristics which may make blood less viable for transfusion. However, not all stored blood spoils at the same rate, a difference that has been attributed to variable rates of energy usage and metabolism in red blood cells. Specific metabolite abundances are heritable traits; however, the link between heritability of energy metabolism and red blood cell storage profiles is unclear. Herein we performed a comprehensive metabolomics and proteomics study of red blood cells from 18 mono- and di-zygotic twin pairs to measure heritability and identify correlations with ATP and other molecular indices of energy metabolism. Without using affinity-based hemoglobin depletion, our work afforded the deepest multi-omic characterization of red blood cell membranes to date (1280 membrane proteins and 330 metabolites), with 119 membrane protein and 148 metabolite concentrations found to be over 30% heritable. We demonstrate a high degree of heritability in the concentration of energy metabolism metabolites, especially glycolytic metabolites. In addition to being heritable, proteins and metabolites involved in glycolysis and redox metabolism are highly correlated, suggesting that crucial energy metabolism pathways are inherited en bloc at distinct levels. We conclude that individuals can inherit a phenotype composed of higher or lower concentrations of these proteins together. This can result in vastly different red blood cells storage profiles which may need to be considered to develop precise and individualized storage options. Beyond guiding proper blood storage, this intimate link in heritability between energy and redox metabolism pathways may someday prove useful in determining the predisposition of an individual toward metabolic diseases. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Investigating the adduct formation of organic mercury species with carbonic anhydrase and hemoglobin from human red blood cell hemolysate by means of LC/ESI-TOF-MS and LC/ICP-MS.

PubMed

Hogeback, Jens; Schwarzer, Miriam; Wehe, Christoph A; Sperling, Michael; Karst, Uwe

2016-01-01

The interaction of mercury species with human erythrocytes is studied to investigate possible high molecular binding partners for mercury species. Human blood hemolysate was spiked with methylmercury and investigated by means of liquid chromatography (LC) coupled to electrospray ionization time of flight mass spectrometry (ESI-ToF-MS) and inductively coupled plasma mass spectrometry (ICP-MS). Beside adduct formation of mercury species with hemoglobin, the main compound of the erythrocytes, mercury binding to the enzyme carbonic anhydrase was revealed. Due to an enzymatic digest of the protein-mercury adduct, the binding site at the free thiol group of the protein was identified. These results indicate that carbonic anhydrase might play a role in mercury toxicity.

THE EFFECTS OF EXPERIMENTAL PLETHORA ON BLOOD PRODUCTION.

PubMed

Robertson, O H

1917-08-01

With the purpose of determining whether a diminished activity of the bone marrow could be brought about experimentally, plethora was produced in rabbits by means of repeated small transfusions of blood. Counts of the number of reticulated red cells in the circulating blood were made during the course of the experiments as an index to changes in the activity of the bone marrow. With the development of plethora, the number of reticulated cells in the blood decreased. In the majority of the plethoric animals, this diminution was extreme, and in some instances, reticulated cells practically disappeared from the blood. A comparison of the red bone marrow of these animals with that of normal controls revealed a marked reduction in the content of reticulated cells. After a number of transfusions, there occurred in some of the plethoric rabbits a sudden and marked drop in hemoglobin. The hemoglobin continued to fall until a severe grade of anemia was reached. This was followed by an extremely rapid regeneration accompanied by a striking rise in color index. During regeneration, the reticulated cells were enormously increased in number. Taken together, these facts show that the bone marrow is markedly influenced by plethora. The diminished number of reticulated cells observed, both in the circulating blood and in the marrow, would make it appear that a decided decrease in blood production occurs. The reduction in the number of these cells cannot be due to changes in the constitution of the red cells put out by the bone marrow, as a result of an increased quantity of hemoglobin in the body, because during regeneration from the above mentioned anemia, when the color index was very high, reticulated cells were still present in large numbers. That the activity of the bone marrow does actually diminish during plethora is further evidenced by the occurrence of the anemia. The most reasonable explanation of this phenomenon is that the recipient develops an immunity against the blood of the donors, which results in the destruction of the strange cells that are in circulation. In keeping with this conception is the appearance of isoagglutinins for the donors' red cells in the blood of the recipient, at about the time of the beginning fall in hemoglobin. The occurrence of anemia as a result of the destruction of the alien blood only would seem to be due to the circumstance that, during the period of plethora, blood production is greatly diminished; as a consequence, the blood cells proper to the recipient are gradually reduced in number and replaced by alien cells until the latter come to constitute the bulk of the animal's blood. In those rabbits developing anemia, the initial drop of hemoglobin from the plethoric level to the normal was constantly accompanied by a marked rise in the number of reticulated cells. This brought up a subsidiary problem for study. With the idea that the stimulation of the bone marrow might be due to the presence of an increased quantity of broken down blood, rabbits, were injected intravenously with large amounts of laked blood cells. The procedure had no evident effect on the blood picture. It was then found that simple blood removal from a plethoric animal which brought back the hemoglobin to the normal level, or even to a point somewhat above, sufficed to cause a marked increase in the number of reticulated cells. Although these findings are not conclusive, they suggest an explanation for the increased bone marrow activity accompanying the initial drop of hemoglobin in the plethoric rabbits; namely, that the organism had in some way adapted itself during the period of plethora to the presence of a greater amount of blood and that the result of blood loss in such an organism was a relative but not absolute anemia. The finding that the activity of the bone marrow can be depressed by the introduction of a large quantity of blood into the circulation accounts for the diminished bone marrow activity which sometimes occurs after transfusion in pernicious anemia. In such cases there is a marked drop in the number of reticulated cells and other evidence of bone marrow depression; the patient shows no benefit from transfusion or may grow rapidly worse. The cause of this depression is best explained on the basis that in severe instances of the disease where exhaustion of the bone marrow is imminent, the stimulus of the anemia is only just sufficient to keep the marrow functioning. A sudden lowering of this stimulus is brought about by the introduction of a large quantity of blood into the circulation, and the result is a fall in the activity of the bone marrow. It follows from this that in pernicious anemia with a feebly reacting bone marrow as indicated by the number of reticulated red cells, small transfusions are preferable to large ones.

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.

Multi-color phase imaging and sickle cell anemia (Conference Presentation)

NASA Astrophysics Data System (ADS)

Hosseini, Poorya; Zhou, Renjie; Yaqoob, Zahid; So, Peter T. C.

2016-03-01

Quantitative phase measurements at multiple wavelengths has created an opportunity for exploring new avenues in phase microscopy such as enhancing imaging-depth (1), measuring hemoglobin concentrations in erythrocytes (2), and more recently in tomographic mapping of the refractive index of live cells (3). To this end, quantitative phase imaging has been demonstrated both at few selected spectral points as well as with high spectral resolution (4,5). However, most of these developed techniques compromise imaging speed, field of view, or the spectral resolution to perform interferometric measurements at multiple colors. In the specific application of quantitative phase in studying blood diseases and red blood cells, current techniques lack the required sensitivity to quantify biological properties of interest at individual cell level. Recently, we have set out to develop a stable quantitative interferometric microscope allowing for measurements of such properties for red cells without compromising field of view or speed of the measurements. The feasibility of the approach will be initially demonstrated in measuring dispersion curves of known solutions, followed by measuring biological properties of red cells in sickle cell anemia. References: 1. Mann CJ, Bingham PR, Paquit VC, Tobin KW. Quantitative phase imaging by three-wavelength digital holography. Opt Express. 2008;16(13):9753-64. 2. Park Y, Yamauchi T, Choi W, Dasari R, Feld MS. Spectroscopic phase microscopy for quantifying hemoglobin concentrations in intact red blood cells. Opt Lett. 2009;34(23):3668-70. 3. Hosseini P, Sung Y, Choi Y, Lue N, Yaqoob Z, So P. Scanning color optical tomography (SCOT). Opt Express. 2015;23(15):19752-62. 4. Jung J-H, Jang J, Park Y. Spectro-refractometry of individual microscopic objects using swept-source quantitative phase imaging. Anal Chem. 2013;85(21):10519-25. 5. Rinehart M, Zhu Y, Wax A. Quantitative phase spectroscopy. Biomed Opt Express. 2012;3(5):958-65.

Leukocyte, red blood cell and morphological adaptation to moderate physical training in rats undernourished in the neonatal period

PubMed Central

Viana, Marcelo Tavares; Perez, Manuella Cavalcanti; Ribas, Valdenilson Ribeiro; Martins, Gilberto de Freire; de Castro, Célia Maria Machado Barbosa

2012-01-01

Objective To analyze the impact of moderate physical exercise on the total and differential leukocyte counts and red blood cell count of 36 sixty-day-old adult male Wistar rats subjected to early malnourishment. Methods The rats were divided in nourished (N - casein 17%) and malnourished groups (M - casein 8%) and thesegroups were then subdivided in trained (T) untrained (U) creating four groups NT, NU, MT and MU. The NT and MTgroups were submitted to moderate physical exercise using a treadmill (60 min/day, 5 days/week for 8 weeks). Onthe 1st day, before the training started T0 and 24 hours after the last training day of the week (T1 until T8), a 1 mLaliquot of blood was collected from the animals' tails for analysis. The total leukocyte count was evaluated in a cellcounter with an electronic microscope. The cyanmethemoglobin technique was used to measure the hemoglobin level. The hematocrit values were determined as a percentage using the micro-hematocrit technique with a microcapillaryreader and a cell counter was used to determine the red blood cell count. The t-test was used for statistical analysis and a p-value < 0.05 was considered significant. Data are expressed as means ± standard deviation. Results There was a significant difference in the total leukocyte count between the NT (9.1 ± 0.1) and MT groups (8.0 ± 0.1) from T1 and in neutrophils between the NT (22.1 ± 0.6) and MT groups (24.6 ± 1.8) from T7 (p < 0.05). There was no statistical significance in the hemoglobin, hematocrit and red blood cell count from T1. Conclusions According to the results of this study, moderate physical exercise seems to have induced physiologic adaptation in adult rats from T1. PMID:23049442

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%.

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.

Red blood cell vesiculation in hereditary hemolytic anemia

PubMed Central

Alaarg, Amr; Schiffelers, Raymond M.; van Solinge, Wouter W.; van Wijk, Richard

2013-01-01

Hereditary hemolytic anemia encompasses a heterogeneous group of anemias characterized by decreased red blood cell survival because of inherited membrane, enzyme, or hemoglobin disorders. Affected red blood cells are more fragile, less deformable, and more susceptible to shear stress and oxidative damage, and show increased vesiculation. Red blood cells, as essentially all cells, constitutively release phospholipid extracellular vesicles in vivo and in vitro in a process known as vesiculation. These extracellular vesicles comprise a heterogeneous group of vesicles of different sizes and intracellular origins. They are described in literature as exosomes if they originate from multi-vesicular bodies, or as microvesicles when formed by a one-step budding process directly from the plasma membrane. Extracellular vesicles contain a multitude of bioactive molecules that are implicated in intercellular communication and in different biological and pathophysiological processes. Mature red blood cells release in principle only microvesicles. In hereditary hemolytic anemias, the underlying molecular defect affects and determines red blood cell vesiculation, resulting in shedding microvesicles of different compositions and concentrations. Despite extensive research into red blood cell biochemistry and physiology, little is known about red cell deformability and vesiculation in hereditary hemolytic anemias, and the associated pathophysiological role is incompletely assessed. In this review, we discuss recent progress in understanding extracellular vesicles biology, with focus on red blood cell vesiculation. Also, we review recent scientific findings on the molecular defects of hereditary hemolytic anemias, and their correlation with red blood cell deformability and vesiculation. Integrating bio-analytical findings on abnormalities of red blood cells and their microvesicles will be critical for a better understanding of the pathophysiology of hereditary hemolytic anemias. PMID:24379786

Phosphatidylserine exposure and red cell viability in red cell aging and in hemolytic anemia.

PubMed

Boas, F E; Forman, L; Beutler, E

1998-03-17

Phosphatidylserine (PS) normally localizes to the inner leaflet of cell membranes but becomes exposed in abnormal or apoptotic cells, signaling macrophages to ingest them. Along similar lines, it seemed possible that the removal of red cells from circulation because of normal aging or in hemolytic anemias might be triggered by PS exposure. To investigate the role of PS exposure in normal red cell aging, we used N-hydroxysuccinimide-biotin to tag rabbit red cells in vivo, then used phycoerythrin-streptavidin to label the biotinylated cells, and annexin V-fluorescein isothiocyanate (FITC) to detect the exposed PS. Flow cytometric analysis of these cells drawn at 10-day intervals up to 70 days after biotinylation indicated that older, biotinylated cells expose more PS. Furthermore, our data match a simple model of red cell senescence that assumes both an age-dependent destruction of senescent red cells preceded by several hours of PS exposure and a random destruction of red cells without PS exposure. By using this model, we demonstrated that the exposure of PS parallels the rate at which biotinylated red cells are removed from circulation. On the other hand, using an annexin V-FITC label and flow cytometry demonstrates that exposed PS does not cause the reduced red cell life span of patients with hemolytic anemia, with the possible exception of those with unstable hemoglobins or sickle cell anemia. Thus, in some cases PS exposure on the cell surface may signal the removal of red cells from circulation, but in other cases some other signal must trigger the sequestration of cells.

Measurement of Hemoglobin Synthesis Rate in Vivo Using a Stable Isotope Method

PubMed Central

Hibbert, Jacqueline M.; Sutherland, George B.; Wright, Luther L.; Wolfe, Luke G.; Wolfe, Kimberly A.; Gao, Shi Ping; Gore, Dennis C.; Abd-Elfattah, Anwar S.

2015-01-01

We developed a method to measure hemoglobin synthesis rate (SynHb) in humans, assuming that free glycine in the red blood cell (RBC) represents free glycine in bone marrow for hemoglobin synthesis. The present rat study examines this assumption of the method and quantifies SynHb in rats. Sprague–Dawley rats (n = 9) were studied, [2-13C]glycine was intravenously infused over 24 h (2.5 mg kg−1 h−1), blood was drawn for glycine and heme isolation, and bone marrow was harvested for glycine isolation. Isotopic enrichments of glycine and heme were measured, fractional hemoglobin synthesis rate (fSynHb% day−1) was calculated, and from this a value for SynHb (mg g−1 day−1) was derived. Mean body weight was 446 ± 10 g (mean ± SE) and hemoglobin concentration was 14 ± 0.5 g dl−1. At 24 h, the mean isotopic enrichment, atom percentage excess (APE), of the RBC free glycine (1.56 ± 0.18 APE) was similar to the bone marrow (1.68 ± 0.15 APE). The rate of incorporation of 13C into heme increased over time from 0.0004 APE/h between 6 and 12 h, to 0.0014 APE/h between 12 and 18 h, and 0.0024 APE/h between 18 and 24 h. Consequently, fSynHb (1.19 ± 0.32, 2.92 ± 0.66, and 4.22 ± 0.56% day−1, respectively) and SynHb (0.11 ± 0.03, 0.28 ± 0.05, and 0.42 ± 0.05 mg g−1 day−1, respectively) showed similar patterns over the 24-h study period. We conclude that (1) enrichment of free glycine in the circulating RBC approximates enrichment of bone marrow free glycine for heme formation and (2) this pattern of hemoglobin synthesis rate is reflecting the characteristic release and gradual maturation of reticulocytes in the circulation. PMID:11262164

Influence of sickle hemoglobin polymerization and membrane properties on deformability of sickle erythrocytes in the microcirculation.

PubMed Central

Dong, C; Chadwick, R S; Schechter, A N

1992-01-01

The rheological properties of normal erythrocytes appear to be largely determined by those of the red cell membrane. In sickle cell disease, the intracellular polymerization of sickle hemoglobin upon deoxygenation leads to a marked increase in intracellular viscosity and elastic stiffness as well as having indirect effects on the cell membrane. To estimate the components of abnormal cell rheology due to the polymerization process and that due to the membrane abnormalities, we have developed a simple mathematical model of whole cell deformability in narrow vessels. This model uses hydrodynamic lubrication theory to describe the pulsatile flow in the gap between a cell and the vessel wall. The interior of the cell is modeled as a Voigt viscoelastic solid with parameters for the viscous and elastic moduli, while the membrane is assigned an elastic shear modulus. In response to an oscillatory fluid shear stress, the cell--modeled as a cylinder of constant volume and surface area--undergoes a conical deformation which may be calculated. We use published values of normal and sickle cell membrane elastic modulus and of sickle hemoglobin viscous and elastic moduli as a function of oxygen saturation, to estimate normalized tip displacement, d/ho, and relative hydrodynamic resistance, Rr, as a function of polymer fraction of hemoglobin for sickle erythrocytes. These results show the transition from membrane to internal polymer dominance of deformability as oxygen saturation is lowered. More detailed experimental data, including those at other oscillatory frequencies and for cells with higher concentrations of hemoglobin S, are needed to apply fully this approach to understanding the deformability of sickle erythrocytes in the microcirculation. The model should be useful for reconciling the vast and disparate sets of data available on the abnormal properties of sickle cell hemoglobin and sickle erythrocyte membranes, the two main factors that lead to pathology in patients with this disease. PMID:1420913

High affinity hemoglobin and Parkinson's disease.

PubMed

Graham, Jeffrey; Hobson, Douglas; Ponnampalam, Arjuna

2014-12-01

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

Regulation of nitrite transport in red blood cells by hemoglobin oxygen fractional saturation.

PubMed

Vitturi, Dario A; Teng, Xinjun; Toledo, José C; Matalon, Sadis; Lancaster, Jack R; Patel, Rakesh P

2009-05-01

Allosteric regulation of nitrite reduction by deoxyhemoglobin has been proposed to mediate nitric oxide (NO) formation during hypoxia. Nitrite is predominantly an anion at physiological pH, raising questions about the mechanism by which it enters the red blood cell (RBC) and whether this is regulated and coupled to deoxyhemoglobin-mediated reduction. We tested the hypothesis that nitrite transport by RBCs is regulated by fractional saturation. Using human RBCs, nitrite consumption was faster at lower fractional saturations, consistent with faster reactions with deoxyheme. A membrane-based regulation was suggested by slower nitrite consumption with intact versus lysed RBCs. Interestingly, upon nitrite addition, intracellular nitrite concentrations attained a steady state that, despite increased rates of consumption, did not change with decreasing oxygen tensions, suggesting a deoxygenation-sensitive step that either increases nitrite import or decreases the rate of nitrite export. A role for anion exchanger (AE)-1 in the control of nitrite export was suggested by increased intracellular nitrite concentrations in RBCs treated with DIDS. Moreover, deoxygenation decreased steady-state levels of intracellular nitrite in AE-1-inhibited RBCs. Based on these data, we propose a model in which deoxyhemoglobin binding to AE-1 inhibits nitrite export under low oxygen tensions allowing for the coupling between deoxygenation and nitrite reduction to NO along the arterial-to-venous gradient.

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.

Genetic basis of congenital erythrocytosis: mutation update and online databases.

PubMed

Bento, Celeste; Percy, Melanie J; Gardie, Betty; Maia, Tabita Magalhães; van Wijk, Richard; Perrotta, Silverio; Della Ragione, Fulvio; Almeida, Helena; Rossi, Cedric; Girodon, François; Aström, Maria; Neumann, Drorit; Schnittger, Susanne; Landin, Britta; Minkov, Milen; Randi, Maria Luigia; Richard, Stéphane; Casadevall, Nicole; Vainchenker, William; Rives, Susana; Hermouet, Sylvie; Ribeiro, M Leticia; McMullin, Mary Frances; Cario, Holger; Chauveau, Aurelie; Gimenez-Roqueplo, Anne-Paule; Bressac-de-Paillerets, Brigitte; Altindirek, Didem; Lorenzo, Felipe; Lambert, Frederic; Dan, Harlev; Gad-Lapiteau, Sophie; Catarina Oliveira, Ana; Rossi, Cédric; Fraga, Cristina; Taradin, Gennadiy; Martin-Nuñez, Guillermo; Vitória, Helena; Diaz Aguado, Herrera; Palmblad, Jan; Vidán, Julia; Relvas, Luis; Ribeiro, Maria Leticia; Luigi Larocca, Maria; Luigia Randi, Maria; Pedro Silveira, Maria; Percy, Melanie; Gross, Mor; Marques da Costa, Ricardo; Beshara, Soheir; Ben-Ami, Tal; Ugo, Valérie

2014-01-01

Congenital erythrocytosis (CE), or congenital polycythemia, represents a rare and heterogeneous clinical entity. It is caused by deregulated red blood cell production where erythrocyte overproduction results in elevated hemoglobin and hematocrit levels. Primary congenital familial erythrocytosis is associated with low erythropoietin (Epo) levels and results from mutations in the Epo receptor gene (EPOR). Secondary CE arises from conditions causing tissue hypoxia and results in increased Epo production. These include hemoglobin variants with increased affinity for oxygen (HBB, HBA mutations), decreased production of 2,3-bisphosphoglycerate due to BPGM mutations, or mutations in the genes involved in the hypoxia sensing pathway (VHL, EPAS1, and EGLN1). Depending on the affected gene, CE can be inherited either in an autosomal dominant or recessive mode, with sporadic cases arising de novo. Despite recent important discoveries in the molecular pathogenesis of CE, the molecular causes remain to be identified in about 70% of the patients. With the objective of collecting all the published and unpublished cases of CE the COST action MPN&MPNr-Euronet developed a comprehensive Internet-based database focusing on the registration of clinical history, hematological, biochemical, and molecular data (http://www.erythrocytosis.org/). In addition, unreported mutations are also curated in the corresponding Leiden Open Variation Database. © 2013 WILEY PERIODICALS, INC.

Evaluation of a pointwise microcirculation assessment method using liquid and multilayered tissue simulating phantoms

NASA Astrophysics Data System (ADS)

Fredriksson, Ingemar; Saager, Rolf B.; Durkin, Anthony J.; Strömberg, Tomas

2017-11-01

A fiber-optic probe-based instrument, designed for assessment of parameters related to microcirculation, red blood cell tissue fraction (fRBC), oxygen saturation (S), and speed resolved perfusion, has been evaluated using state-of-the-art tissue phantoms. The probe integrates diffuse reflectance spectroscopy (DRS) at two source-detector separations and laser Doppler flowmetry, using an inverse Monte Carlo method for identifying the parameters of a multilayered tissue model. Here, we characterize the accuracy of the DRS aspect of the instrument using (1) liquid blood phantoms containing yeast and (2) epidermis-dermis mimicking solid-layered phantoms fabricated from polydimethylsiloxane, titanium oxide, hemoglobin, and coffee. The root-mean-square (RMS) deviations for fRBC for the two liquid phantoms were 11% and 5.3%, respectively, and 11% for the solid phantoms with highest hemoglobin signatures. The RMS deviation for S was 5.2% and 2.9%, respectively, for the liquid phantoms, and 2.9% for the solid phantoms. RMS deviation for the reduced scattering coefficient (μs‧), for the solid phantoms was 15% (475 to 850 nm). For the liquid phantoms, the RMS deviation in average vessel diameter (D) was 1 μm. In conclusion, the skin microcirculation parameters fRBC and S, as well as, μs‧ and D are estimated with reasonable accuracy.

Molecular Controls of the Oxygenation and Redox Reactions of Hemoglobin

PubMed Central

Henkens, Robert; Alayash, Abdu I.; Banerjee, Sambuddha; Crumbliss, Alvin L.

2013-01-01

Abstract Significance: The broad classes of O2-binding proteins known as hemoglobins (Hbs) carry out oxygenation and redox functions that allow organisms with significantly different physiological demands to exist in a wide range of environments. This is aided by allosteric controls that modulate the protein's redox reactions as well as its O2-binding functions. Recent Advances: The controls of Hb's redox reactions can differ appreciably from the molecular controls for Hb oxygenation and come into play in elegant mechanisms for dealing with nitrosative stress, in the malarial resistance conferred by sickle cell Hb, and in the as-yet unsuccessful designs for safe and effective blood substitutes. Critical Issues: An important basic principle in consideration of Hb's redox reactions is the distinction between kinetic and thermodynamic reaction control. Clarification of these modes of control is critical to gaining an increased understanding of Hb-mediated oxidative processes and oxidative toxicity in vivo. Future Directions: This review addresses emerging concepts and some unresolved questions regarding the interplay between the oxygenation and oxidation reactions of structurally diverse Hbs, both within red blood cells and under acellular conditions. Developing methods that control Hb-mediated oxidative toxicity will be critical to the future development of Hb-based blood substitutes. Antioxid. Redox Signal. 18, 2298–2313. PMID:23198874

Red cell alloantibodies in thalassemia major. Results of an Italian cooperative study.

PubMed

Sirchia, G; Zanella, A; Parravicini, A; Morelati, F; Rebulla, P; Masera, G

1985-01-01

Clinical and serological data on 1435 Italian thalassemia major patients were collected during a cooperative study involving 19 centers in 10 regions. The main findings were as follows: 18 percent of the patients were under 6 years of age, 63 percent between 6 and 15, and 19 percent over 15. Forty-one percent had undergone splenectomy. Sixty-two percent of the patients were maintained at pretransfusion hemoglobin levels higher than 10 g per dl, 36 percent between 8 and 10 g per dl, and 2 percent below 8 g per dl. Overall, 5.2 percent of the patients had clinically significant red cell alloantibodies (136 alloantibodies in 74 patients). One-half of the immunized patients had more than one and one-fourth had more than two alloantibodies. The specificities of the 136 alloantibodies were almost exclusively confined to the common antigens of the Rh, Kell, Kidd, and Duffy systems, in that decreasing order of frequency. The antibody screening procedure, using a low-ionic-strength solution antiglobulin test against a three-red-cell panel and the patient's own red cells (autocontrol) with a serum to cell ratio of 100 to 1 was shown to be an adequate technique for red cell antibody detection.

Study on the Mechanism of Interaction between Phthalate Acid Esters and Bovine Hemoglobin.

PubMed

Chi, Zhenxing; Zhao, Jing; You, Hong; Wang, Mingjing

2016-08-03

Phthalate acid esters (PAEs) are widely used in plastic products as a series of chemical softeners. However, PAEs, which now exist in many environmental media such as the atmosphere, water, and soil, have been shown to be environmental endocrine disruptors. Hemoglobin is a functional protein that carries oxygen in the red blood cells of animals. This study aims at revealing the interactions between bovine hemoglobin (BHb) and PAEs using spectroscopic and molecular modeling methods. The results indicate that the selected representative PAEs-dimethyl phthalate (DMP), diethyl phthalate (DEP), and dibutyl phthalate (DBP)-can interact with BHb to form BHb-PAE complexes with one binding site, mainly relying on hydrophobic forces, with the affinity order DMP > DEP > DBP, opposite to the order of side-chain length. The binding of PAEs can cause conformational and micro-environmental changes in BHb, which may affect the physiological functions of Hb. Furthermore, molecular docking was applied to define the specific binding sites, the results of which show that all the three PAEs can bind into the central cavity of BHb. The study contributes to expound the toxic mechanism of PAEs in vivo from the point of hematological toxicology.

Effect of hemoglobin- and Perflubron-based oxygen carriers on common clinical laboratory tests.

PubMed

Ma, Z; Monk, T G; Goodnough, L T; McClellan, A; Gawryl, M; Clark, T; Moreira, P; Keipert, P E; Scott, M G

1997-09-01

Polymerized hemoglobin solutions (Hb-based oxygen carriers; HBOCs) and a second-generation perfluorocarbon (PFC) emulsion (Perflubron) are in clinical trials as temporary oxygen carriers ("blood substitutes"). Plasma and serum samples from patients receiving HBOCs look markedly red, whereas those from patients receiving PFC appear to be lipemic. Because hemolysis and lipemia are well-known interferents in many assays, we examined the effects of these substances on clinical chemistry, immunoassay, therapeutic drug, and coagulation tests. HBOC concentrations up to 50 g/L caused essentially no interference for Na, K, Cl, urea, total CO2, P, uric acid, Mg, creatinine, and glucose values determined by the Hitachi 747 or Vitros 750 analyzers (or both) or for immunoassays of lidocaine, N-acetylprocainamide, procainamide, digoxin, phenytoin, quinidine, or theophylline performed on the Abbott AxSym or TDx. Gentamycin and vancomycin assays on the AxSym exhibited a significant positive and negative interference, respectively. Immunoassays for TSH on the Abbott IMx and for troponin I on the Dade Stratus were unaffected by HBOC at this concentration. Tests for total protein, albumin, LDH, AST, ALT, GGT, amylase, lipase, and cholesterol were significantly affected to various extents at different HBOC concentrations on the Hitachi 747 and Vitros 750. The CK-MB assay on the Stratus exhibited a negative interference at 5 g/L HBOC. HBOC interference in coagulation tests was method-dependent-fibrometer-based methods on the BBL Fibro System were free from interference, but optical-based methods on the MLA 1000C exhibited interferences at 20 g/L HBOC. A 1:20 dilution of the PFC-based oxygen carrier (600 g/L) caused no interference on any of these chemistry or immunoassay tests except for amylase and ammonia on the Vitros 750 and plasma iron on the Hitachi 747.

RED CELL STROMA PROTEIN RICH IN VITAMIN B12 DURING ACTIVE REGENERATION

PubMed Central

Whipple, G. H.; Robscheit-Robbins, F. S.; Bale, W. F.

1955-01-01

During active blood regeneration in anemia in dogs an increase occurs in the stroma protein of the red cells. When vitamin B12 with radioactive cobalt is given at the start of this blood regeneration one finds concentration of labeled B 12 in the stroma protein but not in the hemoglobin. After the acute phase of red cell regeneration is ended the concentration of B12 in stroma protein falls rapidly to very low levels within 2 weeks. Subsequent episodes of red blood cell regeneration seems not to cause remobilization of radioactive cobalt into red cells from other body stores. It appears that the vitamin B12 is a factor of importance in the first steps of stroma protein formation in the first few days of the life of the red cell in the dog. This response in dogs and the response in pernicious anemia to vitamin B12 may have some points in common. Distribution of the B12-radioactive cobalt in the organs and tissues at autopsy has been recorded. Some very suggestive localizations were noted and some variation 1 week and 7 weeks after B12 injections. Radioactive cobalt escapes in the urine during the weeks following B12 injections. PMID:13271685

The effects of deoxygenation of adult and fetal hemoglobin on the synthesis of red cell 2,3-diphosphoglycerate and its in vivo consequences.

PubMed

Oski, F A; Gottlieb, A J; Miller, W W; Delivoria-Papadopoulos, M

1970-02-01

Patients over 1 month of age with arterial oxygen pressures of less than 60 mm Hg were found to have elevated red cell 2,3-diphosphoglycerate (2,3-DPG) levels and blood with a decreased affinity for oxygen. The increase in 2,3-DPG was proportional to the degree of hypoxemia. In patients under 1 month of age this relationship was not observed. Red cells from adults, but not newborns, showed rapid increases in 2,3-DPG when incubated under nitrogen. Adult, but not fetal, deoxyhemoglobin was shown to facilitate in vitro synthesis of 2,3-DPG by binding this organic phosphate and relieving the product inhibition of 2,3-DPG mutase. Throughout a wide range change in oxygen affinity as measured by the P(50) is linear with respect to the 2,3-DPG concentration; a change of 430 mmumoles of 2,3-DPG/ml of red blood corpuscles (RBC) resulting in a change of the P(50) of 1 mm Hg. It appears that the 2,3-DPG of the adult's red cells responds rapidly to metabolic and environmental influences and in turn effects metabolism and the cellular environment. Many of these effects are not shared by the red cells of the newborn.

Proton transfer from imidazole to chloranil studied by FTIR spectroscopy

NASA Astrophysics Data System (ADS)

Sharma, Amit

2018-05-01

Imidazole is incorporated into many important biological molecules. The most obvious is the amino acid histidine, which has an imidazole side chain. Histidine is present in many proteins and enzymes and plays a vital part in the structure and binding functions of hemoglobin. Therefore it is important to study its proton transfer property. In the present work proton transfer from imidazole to chloranil is investigated by Fourier Transform Infra red Spectroscopy.

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.

Depression and anxiety symptoms are associated with white blood cell count and red cell distribution width: A sex-stratified analysis in a population-based study.

PubMed

Shafiee, Mojtaba; Tayefi, Maryam; Hassanian, Seyed Mahdi; Ghaneifar, Zahra; Parizadeh, Mohammad Reza; Avan, Amir; Rahmani, Farzad; Khorasanchi, Zahra; Azarpajouh, Mahmoud Reza; Safarian, Hamideh; Moohebati, Mohsen; Heidari-Bakavoli, Alireza; Esmaeili, Habibolah; Nematy, Mohsen; Safarian, Mohammad; Ebrahimi, Mahmoud; Ferns, Gordon A; Mokhber, Naghmeh; Ghayour-Mobarhan, Majid

2017-10-01

Depression and anxiety are two common mood disorders that are both linked to systemic inflammation. Increased white blood cell (WBC) count and red cell distribution width (RDW) are associated with negative clinical outcomes in a wide variety of pathological conditions. WBC is a non-specific inflammatory marker and RDW is also strongly related to other inflammatory markers. Therefore, we proposed that there might be an association between these hematological inflammatory markers and depression/anxiety symptoms. The primary objective of this study was to examine the association between depression/anxiety symptoms and hematological inflammatory markers including WBC and RDW in a large population-based study. Symptoms of depression and anxiety and a complete blood count (CBC) were measured in 9274 participants (40% males and 60% females) aged 35-65 years, enrolled in a population-based cohort (MASHAD) study in north-eastern Iran. Symptoms of depression and anxiety were evaluated using the Beck Depression and Anxiety Inventories. The mean WBC count increased with increasing severity of symptoms of depression and anxiety among men. Male participants with severe depression had significantly higher values of RDW (p<0.001); however, this relationship was less marked among women (p=0.004). In addition, men (but not women) with severe anxiety symptoms had significantly higher values of RDW (p<0.001). Moreover, there was a negative association between red blood cell (RBC) and mean corpuscular hemoglobin (MCH) and symptoms of depression/anxiety. Our results suggest that higher depression and anxiety scores are associated with an enhanced inflammatory state, as assessed by higher hematological inflammatory markers including WBC and RDW, even after adjusting for potential confounders. Copyright © 2017 Elsevier Ltd. All rights reserved.

Evaluation of arterial oxygen saturation using RGB camera-based remote photoplethysmography

NASA Astrophysics Data System (ADS)

Nishidate, Izumi; Nakano, Kazuya; McDuff, Daniel; Niizeki, Kyuichi; Aizu, Yoshihisa; Haneishi, Hideaki

2018-02-01

Plethysmogram is the periodic variation in blood volume due to the cardiac pulse traveling through the body. Photo-plethysmograph (PPG) has been widely used to assess the cardiovascular system such as heart rate, blood pressure, cardiac output, vascular compliance. We have previously proposed a non-contact PPG imaging method using a digital red-green-blue camera. In the method, the Monte Carlo simulation for light transport is used to specify a relationship among the RGB-values and the concentrations of oxygenated hemoglobin (CHbO) and deoxygenated hemoglobin (CHbR). The total hemoglobin concentration (CHbT) can be calculated as a sum of CHbO and CHbR. Applying the fast Fourier transform (FFT) band pass filters to each pixel of the sequential images for CHbT along the time line, two-dimentional plethysmogram can be reconstructed. In this study, we further extend the method to imaging the arterial oxygen saturation (SaO2). The PPG signals for both CHbO and CHbR are extracted by the FFT band pass filter and the pulse wave amplitudes (PWAs) of CHbO and CHbR are calculated. We assume that the PWA for CHbO and that for CHbR are decreased and increased as SaO2 is decreased. The ratio of PWA for CHbO and that for CHbR are associated to the reference value of SaO2 measured by a commercially available pulse oximeter, which provide an empirical formula to estimate SaO2 from the PPG signal at each pixel of RGB image. In vivo animal experiments with rats during varying the fraction of inspired oxygen (FiO2) demonstrated the feasibility of the proposed method.

Characterization of the increased binding of acetaldehyde to red blood cells in alcoholics.

PubMed

Hernández-Muñoz, R; Baraona, E; Blacksberg, I; Lieber, C S

1989-10-01

Using equilibrium dialysis, we found that acetaldehyde, at the levels commonly occurring after ethanol ingestion, did not bind detectably to plasma proteins, but there was significant binding to red blood cells, more in alcoholics than in nonalcoholics. The binding to red blood cells was inhibited by pyridoxal phosphate and N-ethylmaleimide, suggesting adduction to amino and thiol groups. Binding kinetics were consistent with at least two sites. The one with the highest affinity for acetaldehyde corresponded to hemoglobin. Its affinity and Bmax were not changed in alcoholics, but these binding sites accounted for only 44% of the sites available in the red blood cells of alcoholics and 80% of those in controls. Moreover, this binding was not inhibited by N-ethylmaleimide. There was no detectable binding to red cell ghosts. Nonprotein binding was then assessed by changes in NADH produced by the addition of protein-free fractions of the cells to an alcohol dehydrogenase system in equilibrium; this revealed a second binder of lower affinity, larger capacity and with sensitivity to both inhibitors. This binding (possibly due to thiazolidine formation with cysteine) was enhanced in alcoholics, whose red blood cell cysteine content was doubled. Levels of red blood cell cysteine and acetaldehyde remained high for 2 weeks after withdrawal. Because of the prolonged persistence after withdrawal, these changes may provide new markers of alcoholism.

Genome-wide association study of red blood cell traits in Hispanics/Latinos: The Hispanic Community Health Study/Study of Latinos

PubMed Central

Morrison, Jean V.; Brown, Lisa; Schurmann, Claudia; Chen, Diane D.; Liu, Yong Mei; Auer, Paul L.; Taylor, Kent D.; Papanicolaou, George; Kurita, Ryo; Nakamura, Yukio; Loos, Ruth J. F.; North, Kari E.; Thornton, Timothy A.; Pankratz, Nathan; Bauer, Daniel E.

2017-01-01

Prior GWAS have identified loci associated with red blood cell (RBC) traits in populations of European, African, and Asian ancestry. These studies have not included individuals with an Amerindian ancestral background, such as Hispanics/Latinos, nor evaluated the full spectrum of genomic variation beyond single nucleotide variants. Using a custom genotyping array enriched for Amerindian ancestral content and 1000 Genomes imputation, we performed GWAS in 12,502 participants of Hispanic Community Health Study and Study of Latinos (HCHS/SOL) for hematocrit, hemoglobin, RBC count, RBC distribution width (RDW), and RBC indices. Approximately 60% of previously reported RBC trait loci generalized to HCHS/SOL Hispanics/Latinos, including African ancestral alpha- and beta-globin gene variants. In addition to the known 3.8kb alpha-globin copy number variant, we identified an Amerindian ancestral association in an alpha-globin regulatory region on chromosome 16p13.3 for mean corpuscular volume and mean corpuscular hemoglobin. We also discovered and replicated three genome-wide significant variants in previously unreported loci for RDW (SLC12A2 rs17764730, PSMB5 rs941718), and hematocrit (PROX1 rs3754140). Among the proxy variants at the SLC12A2 locus we identified rs3812049, located in a bi-directional promoter between SLC12A2 (which encodes a red cell membrane ion-transport protein) and an upstream anti-sense long-noncoding RNA, LINC01184, as the likely causal variant. We further demonstrate that disruption of the regulatory element harboring rs3812049 affects transcription of SLC12A2 and LINC01184 in human erythroid progenitor cells. Together, these results reinforce the importance of genetic study of diverse ancestral populations, in particular Hispanics/Latinos. PMID:28453575

Red blood cell membrane water permeability increases with length of ex vivo storage.

PubMed

Alshalani, Abdulrahman; Acker, Jason P

2017-06-01

Water transport across the red blood cell (RBC) membrane is an essential cell function that needs to be preserved during ex vivo storage. Progressive biochemical depletion during storage can result in significant conformational and compositional changes to the membrane. Characterizing the changes to RBC water permeability can help in evaluating the quality of stored blood products and aid in the development of improved methods for the cryopreservation of red blood cells. This study aimed to characterize the water permeability (L p ), osmotically inactive fraction (b), and Arrhenius activation energy (E a ) at defined storage time-points throughout storage and to correlate the observed results with other in vitro RBC quality parameters. RBCs were collected from age- and sex-matched blood donors. A stopped flow spectrophotometer was used to determine L p and b by monitoring changes in hemoglobin autofluorescence when RBCs were exposed to anisotonic solutions. Experimental values of L p were characterized at three different temperatures (4, 20 and 37 °C) to determine the E a . Results showed that L p , b, and E a of stored RBCs significantly increase by day 21 of storage. Degradation of the RBC membrane with length of storage was seen as an increase in hemolysis and supernatant potassium, and a decrease in deformability, mean corpuscular hemoglobin concentration and supernatant sodium. RBC osmotic characteristics were shown to change with storage and correlate with changes in RBC membrane quality metrics. Monitoring water parameters is a predictor of membrane damage and loss of membrane integrity in ex vivo stored RBCs. Copyright © 2017 Elsevier Inc. All rights reserved.

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.

Neuronal Death After Hemorrhagic Stroke In Vitro and In Vivo Shares Features of Ferroptosis and Necroptosis

PubMed Central

Zille, Marietta; Karuppagounder, Saravanan S.; Chen, Yingxin; Gough, Peter J.; Phil, D.; Bertin, John; Finger, Joshua; Milner, Teresa A.; Jonas, Elizabeth A.; Ratan, Rajiv R.

2017-01-01

Background and Purpose Intracerebral hemorrhage (ICH) leads to disability or death with few established treatments. Adverse outcomes following ICH result from irreversible damage to neurons resulting from primary and secondary injury. Secondary injury has been attributed to hemoglobin and its oxidized product hemin from lysed red blood cells. The aim of this study was to identify the underlying cell death mechanisms attributable to secondary injury by hemoglobin and hemin to broaden treatment options. Methods We investigated cell death mechanisms in cultured neurons exposed to hemoglobin or hemin. Chemical inhibitors implicated in all known cell death pathways were employed. Identified cell death mechanisms were confirmed using molecular markers and electron microscopy. Results Chemical inhibitors of ferroptosis and necroptosis protected against hemoglobin- and hemin-induced toxicity. By contrast, inhibitors of caspase-dependent apoptosis, protein or mRNA synthesis, autophagy, mitophagy or parthanatos had no effect. Accordingly, molecular markers of ferroptosis and necroptosis were increased following ICH in vitro and in vivo. Electron microscopy showed that hemin induced a necrotic phenotype. Necroptosis and ferroptosis inhibitors each abrogated death by greater than 80% and had similar therapeutic windows in vitro. Conclusion Experimental ICH shares features of ferroptotic and necroptotic cell death, but not caspase-dependent apoptosis or autophagy. We propose that ferroptosis or necroptotic signaling induced by lysed blood is sufficient to reach a threshold of death that leads to neuronal necrosis and that inhibition of either one of these pathways can bring cells below that threshold to survival. PMID:28250197

Effect of nanosilver on blood parameters in chickens having aflatoxicosis.

PubMed

Gholami-Ahangaran, Majid; Zia-Jahromi, Noosha

2014-03-01

This experiment is designed to investigate the positive effects of commercial nanosilver compound on blood parameters in experimental aflatoxicosis in broiler chickens. For this, 270 one-day-old broiler chickens were randomly divided into six treatment groups with three replicates. The experimental groups were group A: chickens fed with basal diet; group B: chickens fed with 3 ppm productive aflatoxin in basal diet; groups of C, D, E and F received Mycoad (2.5 g/kg diet), Mycoad (2.5 g/kg diet) + productive aflatoxin (3 ppm), Nanocid (2500 ppm), and Nanocid (2500 ppm) + productive aflatoxin (3 ppm) in basal diet, respectively. Results revealed that some of the blood parameters such as mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration lymphocytes, neutrophils, basophils, monocytes, and eosinophils percentage were not affected in this experiment; whereas, hemoglobin percentage and white blood cell (WBC) count in all the groups fed with 3 ppm aflatoxin except nanocid + aflatoxin decreased significantly (p < 0.05). There are no significant differences between the groups that received nanocid + aflatoxin and mycoad + aflatoxin in hemoglobin percentage and WBC count parameters. The red blood cell count and hematocrit in chickens received aflatoxin were significantly lower than other groups (p < 0.05). Therefore, this study suggests that nanocid similar as mycoad can be useful in reducing the adverse effects of aflatoxin on blood parameters in chickens affected with aflatoxicosis.

Cell-free oxygen carriers: scientific foundations, clinical development, and new directions.

PubMed

Winslow, Robert M

2008-10-01

The most significant hurdle to the development of a safe and effective hemoglobin-based oxygen carrier ("blood substitute") is generally thought to be its propensity to cause vasoconstriction in the microcirculation and hypertension. Two theories for this effect are currently being studied: in one, scavenging NO by hemoglobin reduces vasorelaxation; in the other, cell-free hemoglobin oversupplies O2 (a known vasoconstrictor) to vascular walls by facilitated diffusion. While both mechanisms might lead to reduction of local NO concentration, the important distinction between the two is that if the NO scavenging theory is correct, it greatly diminishes the prospects to develop any solution based on free hemoglobin. However, if the O2-oversupply theory is correct, modifications to the hemoglobin molecule can be envisioned that can prevent oversupply and reduce toxicity. This review summarizes the development of Hemospan, a novel modification of human hemoglobin whose design is based on the O2-oversupply theory. Because of its low P50 and increased molecular size, the release of O2 in resistance vessels (arterioles) by Hemospan is restricted, and vasoconstriction is greatly reduced.

Electrocardiographic Presentation, Cardiac Arrhythmias, and Their Management in β-Thalassemia Major Patients.

PubMed

Russo, Vincenzo; Rago, Anna; Papa, Andrea Antonio; Nigro, Gerardo

2016-07-01

Beta-thalassemia major (β-TM) is a genetic hemoglobin disorder characterized by an absent synthesis of globin chains that are essential for hemoglobin formation, causing chronic hemolytic anemia. Clinical management of thalassemia major consists in regular long-life red blood cell transfusions and iron chelation therapy to remove iron introduced in excess with transfusions. Iron deposition in combination with inflammatory and immunogenic factors is involved in the pathophysiology of cardiac dysfunction in these patients. Heart failure and arrhythmias, caused by myocardial siderosis, are the most important life-limiting complications of iron overload in beta-thalassemia patients. Cardiac complications are responsible for 71% of global death in the beta-thalassemia major patients. The aim of this review was to describe the most frequent electrocardiographic abnormalities and arrhythmias observed in β-TM patients, analyzing their prognostic impact and current treatment strategies. © 2016 Wiley Periodicals, Inc.

Effects of winter fasting and refeeding on white-tailed deer blood profiles

USGS Publications Warehouse

DelGiudice, G.D.; Mech, L.D.; Seal, U.S.; Karns, P.D.

1987-01-01

This study examined the effects of dietary protein, fasting, and refeeding on blood characteristics of 9 nonpregnant, female white-tailed deer (Odocoileus virginianus) in captivity from 23 February to 3 May 1984. Percent weight loss was greater in fasted deer than in deer fed diets of 2 crude protein levels. Fasting effects were also observed for hemoglobin (Hb), red blood cell (RBC) counts, packed cell volume (PCV), cholesterol, triglycerides, serum urea nitrogen (SUN), potassium (K), glucose, phosphorus (P), insulin, thyroxine (T4), and total protein (TP). Refeeding influenced cholesterol, sodium (Na), and calcium (Ca). Hemoglobin, PCV, Ca, P, and albumin varied with time in fasted deer. Changes over time in the fed deer occurred for several hematological and serum characteristics. Data are presented to serve as reference values for better understanding of data collected from free-ranging deer under less known conditions.

Drugs for preventing red blood cell dehydration in people with sickle cell disease.

PubMed

Nagalla, Srikanth; Ballas, Samir K

2016-03-04

Sickle cell disease is an inherited disorder of hemoglobin, resulting in abnormal red blood cells. These are rigid and may block blood vessels leading to acute painful crises and other complications. Recent research has focused on therapies to rehydrate the sickled cells by reducing the loss of water and ions from them. Little is known about the effectiveness and safety of such drugs. This is an updated version of a previously published review. To assess the relative risks and benefits of drugs to rehydrate sickled red blood cells. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register.Last search of the Group's Trials Register: 28 November 2015. Randomized or quasi-randomized controlled trials of drugs to rehydrate sickled red blood cells compared to placebo or an alternative treatment. Both authors independently selected studies for inclusion, assessed study quality and extracted data. Of the 51 studies identified, three met the inclusion criteria. The first study tested the effectiveness of zinc sulphate to prevent sickle cell-related crises in a total of 145 participants and showed a significant reduction in painful crises over one and a half years, mean difference -2.83 (95% confidence interval -3.51 to -2.15). However, analysis was restricted due to limited statistical data. Changes to red cell parameters and blood counts were inconsistent. No serious adverse events were noted in the study.The second study was a Phase II dose-finding study of senicapoc (a Gardos channel blocker) compared to placebo. Compared to the placebo group the high dose senicapoc showed significant improvement in change in hemoglobin level, number and proportion of dense red blood cells, red blood cell count and indices and hematocrit. The results with low-dose senicapoc were similar to the high-dose senicapoc group but of lesser magnitude. There was no difference in the frequency of painful crises between the three groups. A subsequent Phase III study of senicapoc was terminated early since there was no difference observed between the treatment and control groups in the primary end point of painful crises. While the results of zinc for reducing sickle-related crises are encouraging, larger and longer-term multicenter studies are needed to evaluate the effectiveness of this therapy for people with sickle cell disease.While the Phase II and the prematurely terminated phase III studies of senicapoc showed that the drug improved red cell survival (depending on dose), this did not lead to fewer painful crises.We will continue to run searches to identify any potentially relevant trials; however, we do not plan to update other sections of the review until new trials are published.

Concurrent measurement of cellular turbidity and hemoglobin to evaluate the antioxidant activity of plants.

PubMed

Bellik, Yuva; Iguer-Ouada, Mokrane

2016-01-01

In past decades, a multitude of analytical methods for measuring antioxidant activity of plant extracts has been developed. However, when using methods to determine hemoglobin released from human erythrocytes treated with ginger extracts, we found hemoglobin concentrations were significantly higher than in untreated control samples. This suggests in the presence of antioxidants that measuring hemoglobin alone is not sufficient to determine hemolysis. We show concurrent measurement of erythrocyte concentration and hemoglobin is essential in such assays, and describe a new protocol based on simultaneous measurement of cellular turbidity and hemoglobin. Copyright © 2015 Elsevier Ltd. All rights reserved.

The effect of Base Transceiver Station waves on some immunological and hematological factors in exposed persons.

PubMed

Taheri, Mohammad; Roshanaei, Ghodratollah; Ghaffari, Jamileh; Rahimnejad, Samira; Khosroshahi, Behzad Nazel; Aliabadi, Mohsen; Eftekharian, Mohammad Mahdi

2017-01-01

Since the number of mobile subscribers has significantly increased in recent years, the installation and deployment of Base Transceiver Station (BTS) antennas sending and receiving signals has become common and inevitable in different regions. In this study, we have tried to evaluate the effect of the waves on some immunological and hematological parameters in exposed individuals. In this study, the exposed and non-exposed individuals were used as the test and control groups, respectively. The test group was healthy people who resided in the vicinity of the Base Transceiver Station (BTS) antenna and received the maximum of radiation. The control group was selected from the healthy individuals that were matched with the exposed group by age. They resided in a distance of Base Transceiver Station (BTS) antenna and received the minimum of radiation. After stating complete explanations and obtaining the consent, the venous blood samples were taken from them. Then, CBC and the level of cytokines including IL-4, IL-10 and interferon γ were performed on the samples and the results were analyzed by SPSS software. In the test group, the whole number of white blood cells, the level of hematocrit, percent of monocytes, eosinophils and basophils were significantly lower than the control group. The number of red blood cells, their average volume and the mean concentration of hemoglobin were notably higher than the controls. There was not observed a significant difference between the two groups in hemoglobin, its mean concentration, platelet count, percent of lymphocytes and neutrophils as well as serum levels of cytokines IL-4, IL-10 and interferon γ . It seems that radiation of mobile phone antennas influenced the blood and immune systems, but further study should be done to exactly determine the targets.

A mobile phone-based approach to detection of hemolysis.

PubMed

Archibong, Edikan; Konnaiyan, Karthik Raj; Kaplan, Howard; Pyayt, Anna

2017-02-15

Preeclampsia and HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome are pregnancy-related complications with high rates of morbidity and mortality. HELLP syndrome, in particular, can be difficult to diagnose. Recent work suggests that elevated levels of free cell hemoglobin in blood plasma can, as early as the first trimester, potentially serve as a diagnostic biomarker for impending complications. We therefore developed a point-of-care mobile phone-based platform that can quickly characterize a patient's level of hemolysis by measuring the color of blood plasma. The custom hardware and software are designed to be easy to use. A sample of the whole blood (~10µL or less) is first collected into a clear capillary tube or microtube, which is then inserted into a low-cost 3D-printed sample holder attached to the phone. A 5-10min period of quiescence allows for gravitational sedimentation of the red blood cells, leaving a layer of yellowish plasma at the top of the tube. The phone camera then photographs the capillary tube and analyzes the color components of the cell-free plasma layer. The software converts these color values to a concentration of free hemoglobin, based on a built-in calibration curve, and reports the patient's hemolysis level: non-hemolyzed, slightly hemolyzed, mildly hemolyzed, frankly hemolyzed, or grossly hemolyzed.. The accuracy of the method is ~1mgdL -1 . This phone-based point-of-care system provides the potentially life-saving advantage of a turnaround time of about 10min (versus 4+hours for conventional laboratory analytical methods) and a cost of approximately one dollar USD (assuming you have the phone and the software are already available). Copyright © 2016 Elsevier B.V. All rights reserved.

Evaluation of Membrane Systems for Washing/Deglycerolizing Packed Red Blood Cells

DTIC Science & Technology

1987-03-20

d process should reduce the ss than 400 mOsm/kg H20 minutes. The plasma should be less than of centrifugal cessfully demonstrated the rane...2000 ml of wash solution in 35 to 45 minutes. The plasma hemoglobin (Hb) concentration in the washed RBCs should be less than 150 mg/dl. During...plasmapheresis, and the concentration of blood plasma applications, the membranes retain blood but remove water and paration that must be accomplished

THE HEMOGLOBIN FUNCTION OF BLOOD AT 4C.

DTIC Science & Technology

depends on the red cell concentration of 2,3- diphosphoglycerate (2,3-DPG), this metabolic intermediate was assayed and oxygen dissociation curves...the storage period in blood stored in CPD than in ACD. If adenine was present the p50 and 2,3-DPG levels declined more rapidly. However, adenine and...inosine in CPD-stored blood allowed the p50 and 2,3-DPG to persist at near normal levels for most of the 3-week storage period. (Author)

Hemoglobin-driven pathophysiology is an in vivo consequence of the red blood cell storage lesion that can be attenuated in guinea pigs by haptoglobin therapy.

PubMed

Baek, Jin Hyen; D'Agnillo, Felice; Vallelian, Florence; Pereira, Claudia P; Williams, Matthew C; Jia, Yiping; Schaer, Dominik J; Buehler, Paul W

2012-04-01

Massive transfusion of blood can lead to clinical complications, including multiorgan dysfunction and even death. Such severe clinical outcomes have been associated with longer red blood cell (rbc) storage times. Collectively referred to as the rbc storage lesion, rbc storage results in multiple biochemical changes that impact intracellular processes as well as membrane and cytoskeletal properties, resulting in cellular injury in vitro. However, how the rbc storage lesion triggers pathophysiology in vivo remains poorly defined. In this study, we developed a guinea pig transfusion model with blood stored under standard blood banking conditions for 2 (new), 21 (intermediate), or 28 days (old blood). Transfusion with old but not new blood led to intravascular hemolysis, acute hypertension, vascular injury, and kidney dysfunction associated with pathophysiology driven by hemoglobin (Hb). These adverse effects were dramatically attenuated when the high-affinity Hb scavenger haptoglobin (Hp) was administered at the time of transfusion with old blood. Pathologies observed after transfusion with old blood, together with the favorable response to Hp supplementation, allowed us to define the in vivo consequences of the rbc storage lesion as storage-related posttransfusion hemolysis producing Hb-driven pathophysiology. Hb sequestration by Hp might therefore be a therapeutic modality for enhancing transfusion safety in severely ill or massively transfused patients.

The protective effects of taurine on acute ammonia toxicity in grass carp Ctenopharynodon idellus.

PubMed

Xing, Xiaodan; Li, Ming; Yuan, Lixia; Song, Meize; Ren, Qianyan; Shi, Ge; Meng, Fanxing; Wang, Rixin

2016-09-01

The four experimental groups were carried out to test the response of grass carp Ctenopharyngodon idella to ammonia toxicity and taurine: group 1 was injected with NaCl, group 2 was injected with ammonium acetate, group 3 was injected with ammonium acetate and taurine, and group 4 was injected taurine. Fish in group 2 had the highest ammonia content in the liver and brain, and alanine, arginine, glutamine, glutamate and glycine contents in liver. Brain alanine and glutamate of fish in group 2 were significantly higher than those of fish in group 1. Malondialdehyde content of fish in group 2 was the highest, but superoxide dismutase and glutathione activities were the lowest. Although fish in group 2 had the lowest red cell count and hemoglobin, the highest alkaline phosphatase, complement C3, C4 and total immunoglobulin contents appeared in this group. In addition, superoxide dismutase and glutathione activities, red cell count and hemoglobin of fish in group 3 were significantly higher than those of fish in group 2, but malondialdehyde content is the opposite. This study indicates that ammonia exerts its toxic effects by interfering with amino acid transport, inducing reactive oxygen species generation and malondialdehyde accumulation, leading to blood deterioration and over-activation of immune response. The exogenous taurine could mitigate the adverse effect of high ammonia level on fish physiological disorder. Copyright © 2016 Elsevier Ltd. All rights reserved.

Low-cost 420nm blue laser diode for tissue cutting and hemostasis

NASA Astrophysics Data System (ADS)

Linden, Kurt J.

2016-03-01

This paper describes the use of a 420 nm blue laser diode for possible surgery and hemostasis. The optical absorption of blood-containing tissue is strongly determined by the absorption characteristics of blood. Blood is primarily comprised of plasma (yellowish extracellular fluid that is approximately 95% water by volume) and formed elements: red blood cells (RBCs), white blood cells (WBCs) and platelets. The RBCs (hemoglobin) are the most numerous, and due to the spectral absorption characteristics of hemoglobin, the optical absorption of blood has a strong relative maximum value in the 420 nm blue region of the optical spectrum. Small, low-cost laser diodes emitting at 420 nm with tens of watts of continuous wave (CW) optical power are becoming commercially available. Experiments on the use of such laser diodes for tissue cutting with simultaneous hemostasis were carried out and are here described. It was found that 1 mm deep x 1 mm wide cuts can be achieved in red meat at a focused laser power level of 3 W moving at a velocity of ~ 1 mm/s. The peripheral necrosis and thermal damage zone extended over a width of approximately 0.5 mm adjacent to the cuts. Preliminary hemostasis experiments were carried out with fresh equine blood in Tygon tubing, where it was demonstrated that cauterization can occur in regions of intentional partial tubing puncture.

SOD2 deficiency in hematopoietic cells in mice results in reduced red blood cell deformability and increased heme degradation

PubMed Central

Mohanty, Joy G.; Nagababu, Enika; Friedman, Jeffrey S.; Rifkind, Joseph M.

2013-01-01

Among the three types of super oxide dismutases (SODs) known, SOD2 deficiency is lethal in neonatal mice owing to cardiomyopathy caused by severe oxidative damage. SOD2 is found in red blood cell (RBC) precursors, but not in mature RBCs. To investigate the potential damage to mature RBCs resulting from SOD2 deficiency in precursor cells, we studied RBCs from mice in which fetal liver stem cells deficient in SOD2 were capable of efficiently rescuing lethally irradiated host animals. These transplanted animals lack SOD2 only in hematopoietically generated cells and live longer than SOD2 knockouts. In these mice, approximately 2.8% of their total RBCs in circulation are iron-laden reticulocytes, with numerous siderocytic granules and increased protein oxidation similar to that seen in sideroblastic anemia. We have studied the RBC deformability and oxidative stress in these animals and the control group by measuring them with a microfluidic ektacytometer and assaying fluorescent heme degradation products with a fluorimeter, respectively. In addition, the rate of hemoglobin oxidation in RBCs from these mice and the control group were measured spectrophotometrically. The results show that RBCs from these SOD2-deficient mice have reduced deformability, increased heme degradation products, and an increased rate of hemoglobin oxidation compared with control animals, indicative of increased RBC oxidative stress. PMID:23142655

PCBP1 and NCOA4 regulate erythroid iron storage and heme biosynthesis

PubMed Central

Ryu, Moon-Suhn; Zhang, Deliang; Protchenko, Olga; Shakoury-Elizeh, Minoo

2017-01-01

Developing erythrocytes take up exceptionally large amounts of iron, which must be transferred to mitochondria for incorporation into heme. This massive iron flux must be precisely controlled to permit the coordinated synthesis of heme and hemoglobin while avoiding the toxic effects of chemically reactive iron. In cultured animal cells, iron chaperones poly rC–binding protein 1 (PCBP1) and PCBP2 deliver iron to ferritin, the sole cytosolic iron storage protein, and nuclear receptor coactivator 4 (NCOA4) mediates the autophagic turnover of ferritin. The roles of PCBP, ferritin, and NCOA4 in erythroid development remain unclear. Here, we show that PCBP1, NCOA4, and ferritin are critical for murine red cell development. Using a cultured cell model of erythroid differentiation, depletion of PCBP1 or NCOA4 impaired iron trafficking through ferritin, which resulted in reduced heme synthesis, reduced hemoglobin formation, and perturbation of erythroid regulatory systems. Mice lacking Pcbp1 exhibited microcytic anemia and activation of compensatory erythropoiesis via the regulators erythropoietin and erythroferrone. Ex vivo differentiation of erythroid precursors from Pcbp1-deficient mice confirmed defects in ferritin iron flux and heme synthesis. These studies demonstrate the importance of ferritin for the vectorial transfer of imported iron to mitochondria in developing red cells and of PCBP1 and NCOA4 in mediating iron flux through ferritin. PMID:28375153

Performance evaluation of Samsung LABGEO(HC10) Hematology Analyzer.

PubMed

Park, Il Joong; Ahn, Sunhyun; Kim, Young In; Kang, Seon Joo; Cho, Sung Ran

2014-08-01

The Samsung LABGEO(HC10) Hematology Analyzer (LABGEO(HC10)) is a recently developed automated hematology analyzer that uses impedance technologies. The analyzer provides 18 parameters including 3-part differential at a maximum rate of 80 samples per hour. To evaluate the performance of the LABGEO(HC10). We evaluated precision, linearity, carryover, and relationship for complete blood cell count parameters between the LABGEO(HC10) and the LH780 (Beckman Coulter Inc) in a university hospital in Korea according to the Clinical and Laboratory Standards Institute guidelines. Sample stability and differences due to the anticoagulant used (K₂EDTA versus K₃EDTA) were also evaluated. The LABGEO(HC10) showed linearity over a wide range and minimal carryover (<1%) for white blood cell, hemoglobin, red blood cell, and platelet parameters. Correlation between the LABGEO(HC10) and the LH780 was good for all complete blood cell count parameters (R > 0.92) except for mean corpuscular hemoglobin concentration. The bias estimated was acceptable for all parameters investigated except for monocyte count. Most parameters were stable until 24 hours both at room temperature and at 4°C. The difference by anticoagulant type was statistically insignificant for all parameters except for a few red cell parameters. The accurate results achievable and simplicity of operation make the unit recommendable for small to medium-sized laboratories.

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

A Bovine Hemoglobin-Based Oxygen Carrier as Pump Prime for Cardiopulmonary Bypass: Reduced Systemic Lactic Acidosis and Improved Cerebral Oxygen Metabolism During Low-flow in a Porcine Model

DTIC Science & Technology

2010-11-10

1 A bovine hemoglobin-based oxygen carrier as pump prime for cardiopulmonary bypass: reduced systemic lactic acidosis and improved cerebral...2010 2. REPORT TYPE Final Report 3. DATES COVERED (From - To) June 2007 - November 2010 4. TITLE AND SUBTITLE A bovine hemoglobin-based oxygen...carrier as pump prime for cardiopulmonary bypass: reduced systemic lactic acidosis and improved cerebral oxygen metabolism during low-flow in a

A historically significant study that at once disproves the membrane (pump) theory and confirms that nano-protoplasm is the ultimate physical basis of life--yet so simple and low-cost that it could easily be repeated in many high school biology classrooms worldwide.

PubMed

Ling, Gilbert N; Ochsenfeld, Margaret M

2008-01-01

In 1889 Abderhalden reported his discovery that there is no (or as shown later, little) sodium ion (Na+) in human red blood cells even though these cells live in a medium rich in Na+. History shows that all major theories of the living cell are built around this basic phenomenon seen in all the living cells that have been carefully examined. One of these theories has been steadily evolving but is yet-to-be widely known. Named the association-induction hypothesis (AIH), it has been presented thus far in four books dated 1962, 1984, 1992 and 2001 respectively. In this theory, the low Na+ in living cells originates from (i) an above-normal molecule-to-molecule interaction among the bulk-phase cell water molecules, in consequence of (ii) their (self-propagating) polarization-orientation by the backbone NHCO groups of (fully-extended) cell protein(s), when (iii) the protein(s) involved is under the control of the electron-withdrawing cardinal adsorbent (EWC), ATP. A mature human red blood cell (rbc) has no nucleus, nor other organelle. 64% of the rbc is water; 35% belongs to a single protein, hemoglobin (Hb). This twofold simplicity allows the concoction of an ultra-simple model (USM) of the red blood cell's cytoplasmic protoplasm, which comprises almost entirely of hemoglobin, water, K+ and ATP. Only in the USM, the ATP has been replaced by an artificial but theoretically authentic EWC, H+ (given as HCl). To test the theory with the aid of the USM, we filled dialysis sacs with a 40% solution of pure (ferri-) hemoglobin followed by incubating the sacs till equilibrium in solutions containing different amounts of HCI (including zero) but a constant (low) concentration of NaCl. We then determined the equilibrium ratio of the Na+ concentration inside the sac over that in the solution outside and refer to this ratio as qNaCl. When no H+ was added, the qNaCl stayed at unity as predicted by the theory. More important (and also predicted by the theory,) when the right amount of H+ had been added, qNaCl fell to the 0.1- 0.3 range found in living red blood (and other) cells. These and other findings presented confirm the AIH's theory of life at the most basic level: in the resting living state, microscopic, or nano-protoplasm, is the ultimate physical basis of life. (See Post Script on page 111.)

Longevity-associated mitochondrial DNA 5178 C/A polymorphism modulates the effects of coffee consumption on erythrocytic parameters in Japanese men: an exploratory cross-sectional analysis.

PubMed

Kokaze, Akatsuki; Ishikawa, Mamoru; Matsunaga, Naomi; Karita, Kanae; Yoshida, Masao; Ohtsu, Tadahiro; Ochiai, Hirotaka; Shirasawa, Takako; Nanri, Hinako; Saga, Nobuyuki; Ohtsu, Iichiro; Hoshino, Hiromi; Takashima, Yutaka

2014-12-20

Mitochondrial DNA 5178 cytosine/adenine (Mt5178 C/A) polymorphism reportedly modulates the effects of coffee consumption on the risk of hypertension, dyslipidemia and abnormal glucose tolerance. The objective of this analysis was to investigate whether Mt5178 C/A polymorphism modifies the effects of coffee consumption on erythrocytic parameters in male Japanese health check-up examinees. A total of 436 men (mean age ± standard deviation, 54.1 ± 7.8 years) were selected from among individuals visiting the hospital for regular medical check-ups. After Mt5178 C/A genotyping, an exploratory cross-sectional analysis assessing the joint effects of Mt5178 C/A polymorphism and coffee consumption on red blood cell counts, hematocrit and hemoglobin was conducted. For Mt5178C genotypic men, after adjustment for age, body mass index, alcohol consumption, habitual smoking and green tea consumption, coffee consumption significantly decreased red blood cell counts (P for trend = 0.022) and hemoglobin (P for trend = 0.035). The risk of anemia, defined as hemoglobin of <14 g/dL, after the aforementioned adjustment, appeared to depend on coffee consumption (P for trend = 0.078), and the adjusted odds ratio for anemia was significantly higher in men who consumed ≥4 cups of coffee per day than in those who consumed <1 cup per day (odds ratio = 3.771, 95% confidence interval: 1.088 to 13.06, P = 0.036). For Mt5178A genotypic men, coffee consumption possibly reduced the risk of anemia (P for trend = 0.049). However, after the aforementioned adjustment, the statistical significance disappeared (P for trend = 0.137). This exploratory cross-sectional analysis suggests that Mt5178 C/A polymorphism modulates the effects of coffee consumption on erythrocytic parameters and the risk of anemia in male Japanese health check-up examinees.

The amphibious fish Kryptolebias marmoratus uses different strategies to maintain oxygen delivery during aquatic hypoxia and air exposure.

PubMed

Turko, Andy J; Robertson, Cayleih E; Bianchini, Kristin; Freeman, Megan; Wright, Patricia A

2014-11-15

Despite the abundance of oxygen in atmospheric air relative to water, the initial loss of respiratory surface area and accumulation of carbon dioxide in the blood of amphibious fishes during emersion may result in hypoxemia. Given that the ability to respond to low oxygen conditions predates the vertebrate invasion of land, we hypothesized that amphibious fishes maintain O2 uptake and transport while emersed by mounting a co-opted hypoxia response. We acclimated the amphibious fish Kryptolebias marmoratus, which are able to remain active for weeks in both air and water, for 7 days to normoxic brackish water (15‰, ~21kPa O2; control), aquatic hypoxia (~3.6kPa), normoxic air (~21 kPa) or aerial hypoxia (~13.6kPa). Angiogenesis in the skin and bucco-opercular chamber was pronounced in air- versus water-acclimated fish, but not in response to hypoxia. Aquatic hypoxia increased the O2-carrying capacity of blood via a large (40%) increase in red blood cell density and a small increase in the affinity of hemoglobin for O2 (P50 decreased 11%). In contrast, air exposure increased the hemoglobin O2 affinity (decreased P50) by 25% without affecting the number of red blood cells. Acclimation to aerial hypoxia both increased the O2-carrying capacity and decreased the hemoglobin O2 affinity. These results suggest that O2 transport is regulated both by O2 availability and also, independently, by air exposure. The ability of the hematological system to respond to air exposure independent of O2 availability may allow extant amphibious fishes, and may also have allowed primitive tetrapods to cope with the complex challenges of aerial respiration during the invasion of land. © 2014. Published by The Company of Biologists Ltd.

Hyporesponsiveness to Darbepoetin Alfa in Patients With Heart Failure and Anemia in the RED-HF Study (Reduction of Events by Darbepoetin Alfa in Heart Failure): Clinical and Prognostic Associations.

PubMed

van der Meer, Peter; Grote Beverborg, Niels; Pfeffer, Marc A; Olson, Kurt; Anand, Inder S; Westenbrink, B Daan; McMurray, John J V; Swedberg, Karl; Young, James B; Solomon, Scott D; van Veldhuisen, Dirk J

2018-02-01

A poor response to erythropoiesis-stimulating agents such as darbepoetin alfa has been associated with adverse outcomes in patients with diabetes mellitus, chronic kidney disease, and anemia; whether this is also true in heart failure is unclear. We performed a post hoc analysis of the RED-HF trial (Reduction of Events by Darbepoetin Alfa in Heart Failure), in which 1008 patients with systolic heart failure and anemia (hemoglobin level, 9.0-12.0 g/dL) were randomized to darbepoetin alfa. We examined the relationship between the hematopoietic response to darbepoetin alfa and the incidence of all-cause death or first heart failure hospitalization during a follow-up of 28 months. For the purposes of the present study, patients in the lowest quartile of hemoglobin change after 4 weeks were considered nonresponders. The median initial hemoglobin change in nonresponders (n=252) was -0.25 g/dL and +1.00 g/dL in the remainder of patients (n=756). Worse renal function, lower sodium levels, and less use of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers were independently associated with nonresponse. Although a low endogenous erythropoietin level helped to differentiate responders from nonresponders, its predictive value in a multivariable model was poor (C statistic=0.69). Nonresponders had a higher rate of all-cause death or first heart failure hospitalization (hazard ratio, 1.25; 95% confidence interval, 1.02-1.54) and a higher risk of all-cause mortality (hazard ratio, 1.30; 95% confidence interval, 1.04-1.63) than responders. A poor response to darbepoetin alfa was associated with worse outcomes in heart failure patients with anemia. Patients with a poor response were difficult to identify using clinical and biochemical biomarkers. URL: https://www.clinicaltrials.gov. Unique identifier: NCT00358215. © 2018 American Heart Association, Inc.

Transport of the highly charged myo-inositol hexakisphosphate molecule across the red blood cell membrane: a phase transfer and biological study.

PubMed

Vincent, Stéphane P; Lehn, Jean-Marie; Lazarte, Jaime; Nicolau, Claude

2002-09-01

To address the problem of delivering highly charged small molecules, such as phytic acid (InsP(6) or IHP), across biological membranes, we investigated an approach based on a non-covalent interaction between transport molecule(s) and IHP. Thus, we synthesized a collection of compounds containing IHP ionically bound to lipophilic (but non-lipidic) ammonium or poly-ammonium cations. First, we assessed the ability of these water-soluble salts to cross a biological membrane by measuring the partition coefficients between human serum and 1-octanol. In view of the ability of IHP to act as potent effector for oxygen release, the O(2)-hemoglobin dissociation curves were then measured for the most efficient salts on whole blood. From both the biological and the physical properties of IHP-ammonium salts we determined that cycloalkylamines (or poly-amines) were the best transport molecules, especially cycloheptyl- and cyclooctylamine. Indeed, the octanol/serum partition coefficient of IHP undecacyclooctylammonium salt, is superior to 1, which is very favorable for potential uptake into the red blood cell membrane. A qualitative correlation was found between the partitioning experiments and the biological evaluations performed on whole blood.

Normal saline is associated with increased sickle red cell stiffness and prolonged transit times in a microfluidic model of the capillary system.

PubMed

Carden, Marcus A; Fay, Meredith; Sakurai, Yumiko; McFarland, Brynn; Blanche, Sydney; DiPrete, Caleb; Joiner, Clinton H; Sulchek, Todd; Lam, Wilbur A

2017-07-01

Vaso-occlusive crisis (VOC) is a complex process that occurs in patients with sickle cell disease (SCD) and is often associated with pain and urgent hospitalization. A major instigator of VOC is microvascular obstruction by pathologically stiffened sickle red blood cells (RBCs), and thus, therapy relies heavily on optimizing intravenous fluid (IVF) hydration to increase RBC deformability. However, no evidence-based guidelines regarding the choice of IVF currently exist. We therefore analyzed alterations in biomechanical properties of sickle RBCs isolated from patients with homozygous SCD (hemoglobin SS) after exposure to different osmolarities of clinical IVF formulations. Atomic force microscopy (AFM) was used to assess stiffness of RBCs after exposure to different IVFs. A microfluidic model of the human capillary system was used to assess transit time (TT) and propensity to occlusion after exposure to the different IVF formulations. Sickle RBCs exposed to normal saline (NS) had increased stiffness, TTs, and propensity to microchannel occlusion compared to other osmolarities. NS, an IVF formulation often used to treat patients with SCD during VOC, may induce localized microvascular obstruction due to alterations of sickle RBC biomechanical properties. © 2017 John Wiley & Sons Ltd.

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

PubMed

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

2012-07-15

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

Hematologic parameters of astrorats flown on SL-3

NASA Technical Reports Server (NTRS)

Lange, R. D.; Andrews, R. B.; Gibson, L. A.; Wright, P.; Dunn, C. D. R.

1985-01-01

Hematologic studies were performed on a group of large and small rats which were sacrificed after flying in life sciences shuttle engineering flight SL-3. The results are presented on flight (F) and control (C) 200 gm rats. The small flight animals demonstrated a significant increase in hematocrits, red blood cell counts, hemoglobins and peripheral blood percentages of neutrophils as well as a decrease in percentage of lymphocytes. Erythropoietin (Ep) determinations were similar for the two groups as were the bone marrow an spleen differential counts. In vitro cultures for erythroid colonies of bone marrow showed that in response to different doses of Ep, in all cases where differnces were statistically significant, the F rats had increased colony counts. The changes in red cell parameters could be caused by a decrease in plasma volume. However, no isotopic studies were possible on this flight and this lack points up the need for such studies to determine the red cell mass and plasma volume.

Hemorheological alterations of red blood cells induced by non-thermal dielectric barrier discharge plasma

NASA Astrophysics Data System (ADS)

Kim, Jeongho; Kim, Jae Hyung; Chang, Boksoon; Choi, Eun Ha; Park, Hun-Kuk

2016-11-01

Atmospheric pressure non-thermal plasma has been introduced in various applications such as wound healing, sterilization of infected tissues, blood coagulation, delicate surgeries, and so on. The non-thermal plasma generates reactive oxygen species (ROS), including ozone. Various groups have reported that the produced ROS influence proliferation and differentiation of cells, as well as apoptosis and growth arrest of tumor cells. In this study, we investigated the effects of non-thermal plasma on rheological characteristics of red blood cells (RBC). We experimentally measured the extent of hemolysis, deformability, and aggregation of red blood cells (RBC) with respect to exposure times of non-thermal plasma. RBC morphology was also examined using field-emission scanning electron microscopy. The absorbance of hemoglobin released from the RBCs increased with increasing exposure time of the non-thermal plasma. Values of the elongation index and aggregation index were shown to decrease significantly with increasing plasma exposure times. Therefore, hemorheological properties of RBCs could be utilized to assess the performance of various non-thermal plasmas.

β-Thalassemia and Polycythemia vera: targeting chronic stress erythropoiesis.

PubMed

Crielaard, Bart J; Rivella, Stefano

2014-06-01

β-Thalassemia and Polycythemia vera are genetic disorders which affect the synthesis of red blood cells, also referred to as erythropoiesis. Although essentially different in clinical presentation - patients with β-thalassemia have an impairment in β-globin synthesis leading to defective erythrocytes and anemia, while patients with Polycythemia vera present with high hemoglobin levels because of excessive red blood cell synthesis - both pathologies may characterized by lasting high erythropoietic activity, i.e. chronic stress erythropoiesis. In both diseases, therapeutic strategies targeting chronic stress erythropoiesis may improve the address phenotype and prevent secondary pathology, such as iron overload. The current review will address the basic concepts of these strategies to reduce chronic stress erythropoiesis, which may have significant clinical implications in the near future. Copyright © 2014 Elsevier Ltd. All rights reserved.

Transformation of membrane nanosurface of red blood cells under hemin action

NASA Astrophysics Data System (ADS)

Kozlova, Elena; Chernysh, Alexander; Moroz, Victor; Gudkova, Olga; Sergunova, Victoria; Kuzovlev, Artem

2014-08-01

Hemin is the product of hemoglobin oxidation. Some diseases may lead to a formation of hemin. The accumulation of hemin causes destruction of red blood cells (RBC) membranes. In this study the process of development of topological defects of RBC membranes within the size range from nanoscale to microscale levels is shown. The formation of the grain-like structures in the membrane (``grains'') with typical sizes of 120-200 nm was experimentally shown. The process of formation of ``grains'' was dependent on the hemin concentration and incubation time. The possible mechanism of membrane nanostructure alterations is proposed. The kinetic equations of formation and transformation of small and medium topological defects were analyzed. This research can be used to study the cell intoxication and analyze the action of various agents on RBC membranes.

Hydroxycarbamide-Induced Changes in E/beta Thalassemia Red Blood Cells

PubMed Central

Sylvia, Singer T.; Elliott, Vichinsky; Sandra, Larkin; Nancy, Olivieri; Nancy, Sweeters; Frans, Kuypers A.

2010-01-01

In thalassemia, fetal hemoglobin (HbF) augmentation with hydroxycarbamide (also known as hydroxyurea) is not always successful. The expected parallel effects on RBC membrane deformability, cell hydration and membrane phospholipid organization, all important for extending RBC life span and increasing Hb, have been infrequently examined. We analyzed these characteristics in 15 non-transfused E/β 0 thalassemia patients treated with HU (mean 10.2 months). Membrane deformability and cell hydration mildly improved in association with increased HbF levels approaching statistical significance (r = 0.51, p=0.06). All measures improved considerably splenectomized patients. These findings underscore the disappointing results of hydroxyurea treatment in clinical trials; and the importance of examining the effect on red cell characteristics for the development and understanding of HbF-enhancing agents. PMID:18821710

Red cell exchange to mitigate a delayed hemolytic transfusion reaction in a patient transfused with incompatible red blood cells.

PubMed

Irani, Mehraboon S; Karafin, Matthew S; Ernster, Luke

2017-02-01

A red cell exchange was performed to prevent a potentially fatal hemolytic transfusion reaction in a patient with anti-e who was transfused with e-antigen unscreened red blood cells during liver transplant surgery. A 64-year-old woman with cirrhosis due to hepatitis C was scheduled to receive a liver transplant. She had a previously documented anti-e, an antibody to the Rh(e)-antigen that is known to cause delayed hemolytic transfusion reactions. Pre-operatively and intra-operatively, she had massive hemorrhage which required transfusion of 34 e-antigen unscreened red blood cells (RBCs) most of which were incompatible. The hemoglobin dropped from 9.1 g/dL on post-operative day (POD)1 to 6.6 g/dL on POD6, with no evidence of blood loss. The bilirubin also increased from 5.0 mg/dL on POD 1 to 11.0 mg/dL on POD 6. As she was also becoming more hemodynamically unstable, a red cell exchange with 10 units of e-negative RBCs was performed on POD 6. She improved clinically and was extubated the following day. A few residual transfused e-positive red cells were detected after the red cell exchange until POD 13. This case illustrates how a red cell exchange can mitigate the potentially harmful effects of a delayed hemolytic transfusion reaction caused by red cell antibodies. With massive intraoperative blood loss it may not be possible to have antigen-negative RBCs immediately available, particularly for the e-antigen, which is present in 98% of the donor population. The ability to perform such a procedure may be life-saving in such patients. J. Clin. Apheresis 32:59-61, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

The effects of deoxygenation of adult and fetal hemoglobin on the synthesis of red cell 2,3-diphosphoglycerate and its in vivo consequences

PubMed Central

Oski, Frank A.; Gottlieb, Arlan J.; Miller, William W.; Delivoria-Papadopoulos, Maria

1970-01-01

Patients over 1 month of age with arterial oxygen pressures of less than 60 mm Hg were found to have elevated red cell 2,3-diphosphoglycerate (2,3-DPG) levels and blood with a decreased affinity for oxygen. The increase in 2,3-DPG was proportional to the degree of hypoxemia. In patients under 1 month of age this relationship was not observed. Red cells from adults, but not newborns, showed rapid increases in 2,3-DPG when incubated under nitrogen. Adult, but not fetal, deoxyhemoglobin was shown to facilitate in vitro synthesis of 2,3-DPG by binding this organic phosphate and relieving the product inhibition of 2,3-DPG mutase. Throughout a wide range change in oxygen affinity as measured by the P50 is linear with respect to the 2,3-DPG concentration; a change of 430 mμmoles of 2,3-DPG/ml of red blood corpuscles (RBC) resulting in a change of the P50 of 1 mm Hg. It appears that the 2,3-DPG of the adult's red cells responds rapidly to metabolic and environmental influences and in turn effects metabolism and the cellular environment. Many of these effects are not shared by the red cells of the newborn. PMID:5411790

Weathered MC252 crude oil-induced anemia and abnormal erythroid morphology in double-crested cormorants (Phalacrocorax auritus) with light microscopic and ultrastructural description of Heinz bodies.

PubMed

Harr, Kendal E; Cunningham, Fred L; Pritsos, Chris A; Pritsos, Karen L; Muthumalage, Thivanka; Dorr, Brian S; Horak, Katherine E; Hanson-Dorr, Katie C; Dean, Karen M; Cacela, Dave; McFadden, Andrew K; Link, Jane E; Healy, Katherine A; Tuttle, Pete; Bursian, Steven J

2017-12-01

Injury assessment of birds following the Deepwater Horizon (DWH) oil spill in 2010 was part of the Natural Resource Damage Assessment. One reported effect was hemolytic anemia with the presence of Heinz bodies (HB) in birds, however, the role of route and magnitude of exposure to oil is unknown. The purpose of the present study was to determine if double-crested cormorants (Phalacocorax auritis; DCCO) exposed orally and dermally to artificially weathered crude oil would develop hemolytic anemia including HB and reticulocytosis. In the oral experiment, sub-adult, mixed-sex DCCOs were fed control (n = 8) or oil-injected fish with a daily target dose of 5 (n = 9) or 10 (n = 9) ml oil/kg for 21 days. Then, subadult control (n = 12) and treated (n = 13) cormorant groups of similar sex-ratio were dermally treated with approximately 13ml of water or weathered MC252 crude oil, respectively, every 3 days for 6 dosages approximating 20% surface coverage. Collected whole blood samples were analyzed by light (new methylene blue) and transmission electron microscopy. Both oral and dermal treatment with weathered DWH MC252 crude oil induced regenerative, but inadequately compensated, anemia due to hemolysis and hematochezia as indicated by decreased packed cell volume, relative increase in reticulocytes with lack of difference in corrected reticulocyte count, and morphologic evidence of oxidant damage at the ultrastructural level. Hemoglobin precipitation, HB formation, degenerate organelles, and systemic oxidant damage were documented. Heinz bodies were typically <2µm in length and smaller than in mammals. These oblong cytoplasmic inclusions were difficult to see upon routine blood smear evaluation and lacked the classic button appearance found in mammalian red blood cells. They could be found as light, homogeneous blue inclusions upon new methylene blue staining. Ultrastructurally, HB appeared as homogeneous, electron-dense structures within the cytosol and lacked membranous structure. Oxidant damage in avian red blood cells results in degenerate organelles and precipitated hemoglobin or HB with different morphology than that found in mammalian red blood cells. Ultrastructural evaluation is needed to definitively identify HB and damaged organelles to confirm oxidant damage. The best field technique based on the data in this study is assessment of PCV with storage of blood in glutaraldehyde for possible TEM analysis. Copyright © 2017 Elsevier Inc. All rights reserved.

Directly observed reversible shape changes and hemoglobin stratification during centrifugation of human and Amphiuma red blood cells.

PubMed

Hoffman, Joseph F; Inoué, Shinya

2006-02-21

This paper describes changes that occur in human and Amphiuma red blood cells observed during centrifugation with a special microscope. Dilute suspensions of cells were layered, in a centrifuge chamber, above an osmotically matched dense solution, containing Nycodenz, Ficoll, or Percoll (Pharmacia) that formed a density gradient that allowed the cells to slowly settle to an equilibrium position. Biconcave human red blood cells moved downward at low forces with minimum wobble. The cells oriented vertically when the force field was increased and Hb sedimented as the lower part of each cell became bulged and assumed a "bag-like" shape. The upper centripetal portion of the cell became thinner and remained biconcave. These changes occurred rapidly and were completely reversible upon lowering the centrifugal force. Bag-shaped cells, upon touching red cells in rouleau, immediately reverted to biconcave disks as they flipped onto a stack. Amphiuma red cells displayed a different type of reversible stratification and deformation at high force fields. Here the cells became stretched, with the nucleus now moving centrifugally, the Hb moving centripetally, and the bottom of the cells becoming thinner and clear. Nevertheless, the distribution of the marginal bands at the cells' rim was unchanged. We conclude that centrifugation, per se, while changing a red cell's shape and the distribution of its intracellular constituents, does so in a completely reversible manner. Centrifugation of red cells harboring altered or missing structural elements could provide information on shape determinants that are still unexplained.

Immune hemolytic anemia associated with probenecid.

PubMed

Sosler, S D; Behzad, O; Garratty, G; Lee, C L; Postoway, N; Khomo, O

1985-09-01

Upon hospital admission a patient was found to have severe anemia and a strongly positive direct antiglobulin test (DAT). The patient was taking probenecid periodically for gout. An antibody was detected in the patient's serum that only reacted with red blood cells (RBCs) when probenecid was added. Eluates from the patient's RBCs, with and without the presence of drug, were nonreactive. Upon the discontinuation of probenecid, the patient's hemoglobin level improved steadily. We believe this to be the first reported case of immune hemolytic anemia associated with probenecid.

Near Infra-Red Spectroscopy to Reduce Prophylactic Fasciotomies for and Missed Cases of Acute Compartment Syndrome in Soldiers Injured in OEF/OIF

DTIC Science & Technology

2013-10-01

demonstrated that NIRS measurement of hemoglobin oxygen saturation in the tibial compartment provided reliable and sensitive correlation to increases...on 60 healthy participants. Our results indicated that NIRS was able to detect changes in oxygen saturation of muscle with exercise in all 60...Model 41 Introduction 42 Over the last two decades, tissue oxygenation saturation (StO2) measured by near infrared 43 spectroscopy (NIRS) has

Multiscale modelling of Flow-Induced Blood Cell Damage

NASA Astrophysics Data System (ADS)

Liu, Yaling; Sohrabi, Salman

2017-11-01

We study red blood cell (RBC) damage and hemolysis at cellular level. Under high shear rates, pores form on RBC membranes through which hemoglobin (Hb) leaks out and increases free Hb content of plasma leading to hemolysis. By coupling lattice Boltzmann and spring connected network models through immersed boundary method, we estimate hemolysis of a single RBC under various shear rates. The developed cellular damage model can be used as a predictive tool for hydrodynamic and hematologic design optimization of blood-wetting medical devices.

Hemoglobin Function and Red Cell Metabolism in Stored Blood

DTIC Science & Technology

1988-04-01

but still worsen ATP maintenance relative to the CPD-A control. Ascorbate (or vitamin C ), at a 10 mM concentration, maintains near normal 2,3-DPG...ORGANIZATION U.S. Army Medical (if applicable) Research & Development Command Contract No. DADAI7-72- C -2005 8c. ADDRESS(City, State, and ZIP Code) 10- SOURCE OF...ATTENTION OF SGRD-RMI-S SUBJECT: Review of Draft Final Report, April 1, 1988, for Contract No. DADAI7-72- C -2005 Ben R. Dawson, M.D. University of

Therapeutic Applications Of Argon Laser

NASA Astrophysics Data System (ADS)

Brunetaud, J. M.; Mosquet, L.; Mordon, S.; Rotteleur, G.

1984-03-01

Argon laser has a C.W. emission and emits several lines between 487 and 544 nm. This radiation is well absorbed by living tissue and especially where there are red pigments (hemoglobin, myoglobin) or black pigments (melanine). Therapeutic applications mainly use thermal effects. By varying the parameters, (optic power, size of exposed area, exposure time) ; one can obtain a coagulation (maximal tissular temperature 60° - 80°) or a vaporization (temperature over 100°). Section occures when the vaporized area is very thin (below 0.5 mm).

Risks Associated with Fresh Whole Blood and Red Blood Cell Transfusions in a Combat Support Hospital

DTIC Science & Technology

2007-01-01

collection of information if it does not display a currently valid OMB control number. 1. REPORT DATE 2007 2 . REPORT TYPE 3 . DATES COVERED 00-00-2007...coagulation function [13, 14] Increased RBC aggregation [28] Increased free hemoglobin [29] Decreased 2 , 3 DPG and tissue perfusion [30] Decreased oxygen...0.07%) were positive for human lymphotropic virus enzyme immunoassay, and none of 2,831 were positive for both human immunodeficiency virus 1/ 2 and

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.

Evaluation of hematological and biochemical parameters of pesticide retailers following occupational exposure to a mixture of pesticides.

PubMed

Neghab, Masoud; Jalilian, Hamed; Taheri, Shekoufeh; Tatar, Mohsen; Haji Zadeh, Zeynab

2018-06-01

This study was undertaken to ascertain whether light occupational exposure to pesticides by retailers might be associated with any liver, kidney, nervous system dysfunction or hematological abnormalities. In this cross-sectional study, 70 male pesticide retailers (cases) and 64 male subjects, randomly selected from the constructions workers of city council contractors, as the referent group, were investigated. Urine and blood samples were taken from all subjects for urine analysis, hematological and biochemical parameters. Data analysis was conducted through SPSS v.19 using t-test and chi-square test. The results of urine analysis showed that the frequency of abnormal urine tests was significantly higher in cases than in referent individuals. Similarly, the results of CBC showed that the mean values of monocyte, hemoglobin, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin and platelet distribution width were significantly lower, and mean corpuscular hemoglobin concentration and red blood cell distribution width were significantly higher in retailers. No significant differences were found for other parameters. These findings indicate that an association exists between exposure to pesticides by retailers and early subtle and sub-clinical changes in the urine tests and hematological parameters. Engineering measures are recommended to eliminate exposure to pesticides and to prevent its associated outcomes. Copyright © 2018 Elsevier Inc. All rights reserved.

Hematology and erythrocyte osmotic fragility of the Franquet's fruit bat (Epomops franqueti).

PubMed

Ekeolu, Oyetunde Kazeem; Adebiyi, Olamide Elizabeth

2018-03-15

Hematological parameters are vital diagnostic tools for understanding health dynamics of humans and animals. Franquet's fruit bat (Epomops franqueti) is host to several parasites such as protozoa, bacteria, viruses and mites. Yet, studies exploring the values of its blood components with interest for research or food purposes are scarce. Thus, this study was carried out to investigate the hematological values of the adult E. franqueti. Seventeen (nine female and eight male) apparently healthy adult E. franqueti were captured from their roosting colony. Blood samples were collected for determination of erythrocyte indices [red blood cell count (RBC), packed cell volume (PCV), hemoglobin (Hb) concentration, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH) and mean corpuscular hemoglobin concentration (MCHC)] and leukocyte indices [total white blood cell counts (WBC), lymphocytes, eosinophil, monocytes, neutrophil count and erythrocytes osmotic fragility]. There were no significant (p≥0.05) sex-related differences in RBC, PCV, Hb concentration, MCV, MCH, MCHC and total and differential WBC of E. franqueti. Erythrocyte osmotic fragility was significantly higher in female than in male E. franqueti at 0.1% NaCl. These considerations are critical in establishing reference ranges of blood parameters for E. franqueti and may provide insight to why they serve as reservoir hosts for several microorganisms.

Ecotoxicological impacts of clofibric acid and diclofenac in common carp (Cyprinus carpio) fingerlings: hematological, biochemical, ionoregulatory and enzymological responses.

PubMed

Saravanan, Manoharan; Karthika, Subramanian; Malarvizhi, Annamalai; Ramesh, Mathan

2011-11-15

Investigation on the toxic effects of pharmaceutical drugs namely clofibric acid (CA) and diclofenac (DCF) were studied in a common carp Cyprinus carpio at different concentrations such as 1, 10 and 100 μg L(-1) for a short-term period of 96 h under static bioassay method. At all concentrations, red blood cell (RBC), plasma sodium (Na(+)), potassium (K(+)), and glutamate oxaloacetate transaminase (GOT) levels were decreased in fish treated with CA and DCF. Contrastingly, white blood cell (WBC), plasma glucose, protein, lactate dehydrogenase (LDH) and gill Na(+)/K(+)-ATPase level were increased. However, a mixed trend was observed in hemoglobin (Hb), hematocrit (Hct), plasma chloride (Cl(-)), mean cellular volume (MCV), mean cellular hemoglobin (MCH), mean cellular hemoglobin concentration (MCHC) and glutamate pyruvate transaminase (GPT) levels. There was a significant (P<0.01 and P<0.05) change in all parameters measured in fish exposed to different concentrations of CA and DCF. In summary, the alterations in hematological, biochemical, ionoregulatory and enzymological parameters can be used as biomarkers in monitoring the toxicity of CA and DCF in aquatic environment. However, more detailed studies on using of specific biomarkers to monitor the human pharmaceuticals are needed. Copyright © 2011 Elsevier B.V. All rights reserved.

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

PubMed Central

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

2008-01-01

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

Alteration of Blood Parameters and Histoarchitecture of Liver and Kidney of Silver Barb after Chronic Exposure to Quinalphos

PubMed Central

Mohammod Mostakim, Golam; Zahangir, Md. Mahiuddin; Monir Mishu, Mahbuba; Rahman, Md. Khalilur; Islam, M. Sadiqul

2015-01-01

Quinalphos (QP) is commonly used for pest control in the agricultural fields surrounding freshwater reservoirs. This study was conducted to evaluate the chronic toxicity of this pesticide on blood parameters and some organs of silver barb, Barbonymus gonionotus. Fish were exposed to two sublethal concentrations, 0.47 ppm and 0.94 ppm, of QP for a period of 28 days. All the blood parameters (red blood cell, hematocrit, and hemoglobin) and blood glucose except for white blood cells decreased with increasing concentration of toxicant and become significantly lower (p < 0.05) at higher concentration when compared with control. The derived hematological indices of mean corpuscular volume, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration were equally altered compared to control. Histoarchitectural changes of liver and kidney were observed after exposure to the QP. Hypertrophy of hepatocytes, mild to severe necrosis, ruptured central vein, and vacuolation were observed in the liver of treated groups. Highly degenerated kidney tubules and hematopoietic tissue, degeneration of renal corpuscle, vacuolization, and necrosis were evident in the kidney of treated groups. In conclusion, chronic exposure to QP at sublethal concentrations induced hematological and histological alterations in silver barb and offers a simple tool to evaluate toxicity derived alterations. PMID:26635877

Weights and hematology of wild black bears during hibernation

USGS Publications Warehouse

DelGiudice, Glenn D.; Rogers, Lynn L.; Allen, Arthur W.; Seal, U.S.

1991-01-01

We compared weights and hematological profiles of adult (greater than 3-yr-old) female black bears (Ursus americanus) during hibernation (after 8 January). We handled 28 bears one to four times (total of 47) over 4 yr of varying mast and berry production. Mean weight of lactating bears was greater (P less than 0.0001) than that of non-lactating females. White blood cells (P less than 0.05) and mean corpuscular volume (P = 0.005) also differed between lactating and non-lactating bears. Hemoglobin (P = 0.006) and mean corpuscular hemoglobin concentration (P = 0.02) varied among years; values were lowest during 1975, following decreased precipitation and the occurrence of a second year of mast and berry crop shortages in a three-year period. Significant (P less than 0.05) interaction between reproductive status (lactating versus non-lactating) and study year for hemoglobin, red blood cells, and packed cell volume, and increased mean corpuscular volume, suggested a greater nutritional challenge for lactating females compared to non-lactating females during the 1975 denning season. Our data suggest that hematological characteristics of denning bears may be more sensitive than weights as indicators of annual changes in nutritional status; however, other influential factors, in addition to mast and berry crop production, remain to be examined.

The Impact of Red Blood Cell Transfusion on Cerebral Tissue Oxygen Saturation in Severe Traumatic Brain Injury.

PubMed

McCredie, Victoria A; Piva, Simone; Santos, Marlene; Xiong, Wei; de Oliveira Manoel, Airton Leonardo; Rigamonti, Andrea; Hare, Gregory M T; Chapman, Martin G; Baker, Andrew J

2017-04-01

There are a range of opinions on the benefits and thresholds for the transfusion of red blood cells in critically ill patients with traumatic brain injury (TBI) and an urgent need to understand the neurophysiologic effects. The aim of this study was to examine the influence of red blood cell transfusions on cerebral tissue oxygenation (SctO 2 ) in critically ill TBI patients. This prospective observational study enrolled consecutive TBI patients with anemia requiring transfusion. Cerebral tissue oxygen saturation (SctO 2 ) was measured noninvasively with bilateral frontal scalp probes using near-infrared spectroscopy (NIRS) technology. Data were collected at baseline and for 24 h after transfusion. The primary outcome was the applicability of a four-wavelength near-infrared spectrometer to monitor SctO 2 changes during a transfusion. Secondary outcomes included the correlation of SctO 2 with other relevant physiological variables, the dependence of SctO 2 on baseline hemoglobin and transfusion, and the effect of red blood cell transfusion on fractional tissue oxygen extraction. We enrolled 24 patients with severe TBI, of which five patients (21 %) were excluded due to poor SctO 2 signal quality from large subdural hematomas and bifrontal decompressive craniectomies. Twenty transfusions were monitored in 19 patients. The mean pre- and post-transfusion hemoglobin concentrations were significantly different [74 g/L (SD 8 g/L) and 84 g/L (SD 9 g/L), respectively; p value <0.0001]. Post-transfusion SctO 2 was not significantly greater than pre-transfusion SctO 2 [left-side pre-transfusion 69 % (SD 7) vs. post-transfusion 70 % (SD 10); p = 0.68, and right-side pre-transfusion 69 % (SD 5) vs. post-transfusion 71 % (SD 7); p = 0.11]. In a multivariable mixed linear analysis, mean arterial pressure was the only variable significantly associated with a change in SctO 2 . The bifrontal method of recording changes in NIRS signal was not able to detect a measurable impact on SctO 2 in this sample of patients receiving red blood cell transfusion therapy in a narrow but conventionally relevant, range of anemia.

Blood replacement with nanobiotechnologically engineered hemoglobin and hemoglobin nanocapsules

PubMed Central

Chang, Thomas Ming Swi

2012-01-01

Unlike donor red blood cells (RBCs), blood substitutes can be treated to remove infective agents and can be used on the spot or in the ambulance in emergency without the time-consuming typing and cross-matching. Donor RBC requires storage at 4° and is only good for 42 days, but blood substitutes can be stored for much longer time. For example, a bovine polyhemoglobin (PolyHb) can be stored at room temperature for more than 1 year. It has been shown as far back as 1957 that artificial RBC can be prepared with ultrathin polymer membranes of nanodimension thickness. To increase the circulation time, the first-generation engineered hemoglobin (Hb) is formed by using glutaraldehyde to crosslink Hb into soluble nanodimension PolyHb that has been tested clinically in patients. Further extension includes conjugated Hb, intramolecularly crosslinked Hb and recombinant Hb. For certain clinical uses, in addition to engineered Hb, we also need antioxidants to remove oxygen radicals to prevent injury from ischemia reperfusion. Thus, we use nanobiotechnology to prepare second-generation engineered Hb by assembling Hb together with superoxide dismutase (SOD) and catalase (CAT) to form a nanodimension soluble complex of polyhemoglobin (PolyHb)-CAT-SOD. A third generation system is to prepare nanodimension complete artificial RBCs that can circulate for sufficient length of time after infusion. One approach uses lipid vesicles to encapsulate hemoglobin (Hb). Another approach is to use biodegradable polymer-like polylactic acid or a copolymer of polyethylene glycol-polylactide (PEG-PLA) to form the membrane of nanodimension complete artificial RBC (www.artcell.mcgill.ca). PMID:20564467

Erythropoietin reduces anemia and transfusions after chemotherapy with paclitaxel and carboplatin.

PubMed

Dunphy, F R; Dunleavy, T L; Harrison, B R; Boyd, J H; Varvares, M A; Dunphy, C H; Rodriguez, J J; McDonough, E M; Minster, J R; McGrady, M D

1997-04-15

The authors report on anemia observed during preoperative paclitaxel and carboplatin chemotherapy in patients with advanced head and neck carcinoma and discuss how the use of recombinant human erythropoietin (r-HuEPO) ameliorates this anemia, reducing the need for subsequent packed red blood cell (PRBC) transfusions. Response to r-HuEPO was defined as reduced hemoglobin fall during preoperative chemotherapy and reduced transfusion requirements during surgery. Thirty-six patients with advanced head and neck carcinoma were evaluable after treatment with preoperative chemotherapy using paclitaxel and carboplatin. Group 1 was comprised of 14 patients who empirically received r-HuEPO at a dose of 150 U/kg 3 times per week for 3 weeks; in patients deemed nonresponders, the dose was increased to 300 U/kg and 450 U/kg in the subsequent courses. Group 2 was comprised of 22 patients who did not receive r-HuEPO. During preoperative chemotherapy, the mean hemoglobin fall was 0.5 g/dL in Group 1 (P = 0.40). In Group 2 there was a statistically significant mean hemoglobin fall of 3.3 g/dL (P < 0.0001). There was also a nonstatistically significant trend toward fewer PRBC transfusions: none of 14 patients (0%) in Group 1 versus 4 of 22 patients (18%) in Group 2 (P = 0.141). A significant fall in hemoglobin and an increase in the need for transfusions were observed in head and neck carcinoma patients receiving carboplatin and paclitaxel chemotherapy prior to surgery. Empiric r-HuEPO therapy appeared to prevent anemia and reduced the need for PRBC transfusions.

Anemia and Dental Caries in Pregnant Women: a Prospective Cohort Study.

PubMed

Costa, Elisa Miranda; Azevedo, Juliana A P; Martins, Rafiza F M; Alves, Cláudia M C; Ribeiro, Cecília C C; Thomaz, Erika B A F

2017-06-01

The objective was to evaluate the effect of anemia during pregnancy on the risk of dental caries development in pregnant women. A prospective cohort including a sample of pregnant women in a prenatal care unit of São Luís, Brazil, was done. The incidence of dental caries during pregnancy, according to Nyvad's criteria, was the outcome. The main independent variables were serum iron, ferritin, hemoglobin, erythrocyte, hematocrit, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), and red cell distribution width (RDW). Pregnant women (n = 121) were evaluated at two moments: up to 16th week of gestational age (T1) and in the last trimester of pregnancy (T2). Crude and adjusted associations were estimated by the incidence ratio risk (IRR) and respective 95% confidence intervals (95%CI). After adjustment, higher serum concentrations of ferritin (IRR = 0.97, 95%CI 0.95-0.99) in T1, and Fe (IRR = 0.99, 95%CI 0.98-0.99), ferritin (IRR = 0.99, 95%CI 0.98-0.99), erythrocyte (IRR = 0.71, 95%CI 0.50-0.99), hemoglobin (IRR = 0.84, 95%CI 0.73-0.96), hematocrit (IRR = 0.93, 95%CI 0.88-0.98), MCV (IRR = 0.91, 95%CI 0.86-0.96), and MCH (IRR = 0.83, 95%CI 0.74-0.93) in T2, were associated with fewer incidence of dental caries in pregnant women. Iron deficiency anemia during pregnancy is a risk factor for the incidence of dental caries in these women.

Physiological and hematological changes in Chum Salmon artificially infected with Erythrocytic Necrosis virus

USGS Publications Warehouse

Haney, D.C.; Hursh, D.A.; Mix, M.C.; Winton, J.R.

1992-01-01

Chum salmon Oncorhynchus keta were injected with erythrocytic necrosis virus (ENV) to study the physiological and hematological consequences of ENV infection. Infected and control fish were held in pathogen-free seawater and sampled for 5 weeks. Physiological tests included measures of plasma cortisol, glucose, protein, and osmolality; blood lactic acid; and liver glycogen. In general, ENV-infected fish had lower plasma glucose and blood lactic acid, and higher liver glycogen concentrations than did control fish. Hematological tests included red and white blood cell (RBC and WBC) counts, hematocrit, measurement of blood hemoglobin concentration, and a determination of erythrocyte fragility. Infected fish had lower RBC counts, hematocrits, and hemoglobin concentrations; higher WBC counts; and less fragile erythrocytes than did control fish. The hematology data indicated that erythrocytes of infected fish had higher mean corpuscular volume, depressed mean corpuscular hemoglobin concentration, and slightly lower mean corpuscular hemoglobin. Erythrocytic inclusions were observed in the cytoplasm of RBCs from infected fish. The infection progressed steadily through week 4, after which the fish appeared to begin recovering. In a second study, fish were infected with ENV for 3 weeks, and recovery from a stress challenge test was measured. Plasma glucose concentrations and osmclality were higher in infected fish, whereas plasma cortisol and blood lactate were only slightly elevated. These studies indicate that chum salmon withstood the effects of ENV infection without in-eversible physiological consequences. However, when subjected to a stress challenge test, infected fish recovered more slowly than control fish and had increased osmoregulatory difficulties.

Biophysical Characterisation of Neuroglobin of the Icefish, a Natural Knockout for Hemoglobin and Myoglobin. Comparison with Human Neuroglobin

PubMed Central

Giordano, Daniela; Boron, Ignacio; Abbruzzetti, Stefania; Van Leuven, Wendy; Nicoletti, Francesco P.; Forti, Flavio; Bruno, Stefano; Cheng, C-H. Christina; Moens, Luc; di Prisco, Guido; Nadra, Alejandro D.; Estrin, Darío; Smulevich, Giulietta; Dewilde, Sylvia; Viappiani, Cristiano; Verde, Cinzia

2012-01-01

The Antarctic icefish Chaenocephalus aceratus lacks the globins common to most vertebrates, hemoglobin and myoglobin, but has retained neuroglobin in the brain. This conserved globin has been cloned, over-expressed and purified. To highlight similarities and differences, the structural features of the neuroglobin of this colourless-blooded fish were compared with those of the well characterised human neuroglobin as well as with the neuroglobin from the retina of the red blooded, hemoglobin and myoglobin-containing, closely related Antarctic notothenioid Dissostichus mawsoni. A detailed structural and functional analysis of the two Antarctic fish neuroglobins was carried out by UV-visible and Resonance Raman spectroscopies, molecular dynamics simulations and laser-flash photolysis. Similar to the human protein, Antarctic fish neuroglobins can reversibly bind oxygen and CO in the Fe2+ form, and show six-coordination by distal His in the absence of exogenous ligands. A very large and structured internal cavity, with discrete docking sites, was identified in the modelled three-dimensional structures of the Antarctic neuroglobins. Estimate of the free-energy barriers from laser-flash photolysis and Implicit Ligand Sampling showed that the cavities are accessible from the solvent in both proteins. Comparison of structural and functional properties suggests that the two Antarctic fish neuroglobins most likely preserved and possibly improved the function recently proposed for human neuroglobin in ligand multichemistry. Despite subtle differences, the adaptation of Antarctic fish neuroglobins does not seem to parallel the dramatic adaptation of the oxygen carrying globins, hemoglobin and myoglobin, in the same organisms. PMID:23226490

Red cell density is sex and race dependent in the adult.

PubMed

Blumenfeld, N; Fabry, M E; Thysen, B; Nagel, R L

1988-09-01

Using a highly sensitive method for the determination of red cell densities (Percoll-Stractan continuous isopyknic gradients), we find that, in adults, this parameter varies with sex and race. Whites have red cell densities (expressed as mean corpuscular hemoglobin concentration [MCHC]) that are, on the average, 0.7 gm/dl higher than those in blacks (the difference of the means has p less than 2 x 10(-7]. White men have, on the average, 0.6 gm/dl higher MCHC than white women (the difference of the means has p less than 6 x 10(-5]. We find a strong correlation between all red cell densities and intracellular K+ and a slightly weaker correlation between red cell density and intracellular Na+ + K+. Men have an average intraerythrocytic K+ that is approximately 4.5 mmol/L of red cells less than that of women among whites as well as blacks (p less than 10(-5) and p less than 9 x 10(-4), respectively). Blacks have significantly higher plasma ferritin levels than do whites (in addition to the sex difference). Future work will have to dissect the possible causes of these differences, which include the high incidence of deletional alpha-thalassemia (-a/aa) among blacks, menstruation, hormonal effects, and the red cell transport and volume regulation differences between sexes and races. Whatever the cause of the sex and racial differences reported here, they are bound to affect the pathophysiologic expression of genetic red cell diseases that are particularly sensitive to the MCHC, such as the sickle cell syndromes.

The Use of an Acellular Oxygen Carrier in a Human Liver Model of Normothermic Machine Perfusion.

PubMed

Laing, Richard W; Bhogal, Ricky H; Wallace, Lorraine; Boteon, Yuri; Neil, Desley A H; Smith, Amanda; Stephenson, Barney T F; Schlegel, Andrea; Hübscher, Stefan G; Mirza, Darius F; Afford, Simon C; Mergental, Hynek

2017-11-01

Normothermic machine perfusion of the liver (NMP-L) is a novel technique that preserves liver grafts under near-physiological conditions while maintaining their normal metabolic activity. This process requires an adequate oxygen supply, typically delivered by packed red blood cells (RBC). We present the first experience using an acellular hemoglobin-based oxygen carrier (HBOC) Hemopure in a human model of NMP-L. Five discarded high-risk human livers were perfused with HBOC-based perfusion fluid and matched to 5 RBC-perfused livers. Perfusion parameters, oxygen extraction, metabolic activity, and histological features were compared during 6 hours of NMP-L. The cytotoxicity of Hemopure was also tested on human hepatic primary cell line cultures using an in vitro model of ischemia reperfusion injury. The vascular flow parameters and the perfusate lactate clearance were similar in both groups. The HBOC-perfused livers extracted more oxygen than those perfused with RBCs (O2 extraction ratio 13.75 vs 9.43 % ×10 per gram of tissue, P = 0.001). In vitro exposure to Hemopure did not alter intracellular levels of reactive oxygen species, and there was no increase in apoptosis or necrosis observed in any of the tested cell lines. Histological findings were comparable between groups. There was no evidence of histological damage caused by Hemopure. Hemopure can be used as an alternative oxygen carrier to packed red cells in NMP-L perfusion fluid.

Nitric oxide in red blood cell adaptation to hypoxia.

PubMed

Zhao, Yajin; Wang, Xiang; Noviana, Milody; Hou, Man

2018-06-01

Nitric oxide (NO) appears to be involved in virtually every aspect of cardiovascular biology. Most attention has been focused on the role of endothelial-derived NO in basal blood flow regulation by relaxing vascular smooth muscle; however, it is now known that NO derived from red blood cells (RBCs) plays a fundamental role in vascular homeostasis by enhancing oxygen (O2) release at the cellular and physiological level. Hypoxia is an often seen problem in diverse conditions; systemic adaptations to hypoxia permit people to adjust to the hypoxic environment at high altitudes and to disease processes. In addition to the cardiopulmonary and hematologic adaptations that support systemic O2 delivery in hypoxia, RBCs assist through newly described NO-based mechanisms, in line with their vital role in O2 transport and delivery. Furthermore, to increase the local blood flow in proportion to metabolic demand, NO regulates membrane mechanical properties thereby modulating RBC deformability and O2 carrying-releasing function. In this review article, we focus on the effect of NO bioactivity on RBC-based mechanisms that regulate blood flow and RBC deformability. RBC adaptations to hypoxia are summarized, with particular attention to NO-dependent S-nitrosylation of membrane proteins and hemoglobin (S-nitrosohemoglobin). The NO/S-nitrosylation/RBC vasoregulatory cascade contributes fundamentally to the molecular understanding of the role of NO in human adaptation to hypoxia and may inform novel therapeutic strategies.

Establishment of new complete blood count reference values for healthy Thai adults.

PubMed

Wongkrajang, P; Chinswangwatanakul, W; Mokkhamakkun, C; Chuangsuwanich, N; Wesarachkitti, B; Thaowto, B; Laiwejpithaya, S; Komkhum, O

2018-04-28

Laboratory reference ranges are essential for diagnostic orientation and treatment decision. As complete blood count parameters are influenced by various factors, including gender, geographic origin, and ethnic origin, it is important to establish specific hematologic reference values for specific populations. This study was conducted at the Department of Clinical Pathology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand. Blood samples were taken from healthy adults aged 18-60 years that attended a health check-up program at our hospital during February 2015 to July 2015. Hematologic and routine chemistry analysis were performed. Participants were determined to be healthy based on medical history and routine medical examinations. Serum vitamin B12, folate, ferritin, and hemoglobin typing were also analyzed to exclude the possible presence of anemia. A statistically significant difference was observed between males and females for Hb level, hematocrit level, red blood cell count, mean corpuscular hemoglobin concentration, percentage neutrophils, monocytes and eosinophils, and absolute neutrophil, lymphocyte, basophil, and platelet counts. Accordingly, gender-specific reference intervals were established for all complete blood count parameters in healthy Thai adult population. The reference value ranges established in this study reflect significant differences between genders. It is possible that these reference ranges may be generalizable to adults living in Thailand. The findings of this study emphasize the importance of establishing specific hematologic reference values for specific populations. © 2018 John Wiley & Sons Ltd.

The use of biomarkers to describe plasma-, red cell-, and blood volume from a simple blood test.

PubMed

Lobigs, Louisa Margit; Sottas, Pierre-Edouard; Bourdon, Pitre Collier; Nikolovski, Zoran; El-Gingo, Mohamed; Varamenti, Evdokia; Peeling, Peter; Dawson, Brian; Schumacher, Yorck Olaf

2017-01-01

Plasma volume and red cell mass are key health markers used to monitor numerous disease states, such as heart failure, kidney disease, or sepsis. Nevertheless, there is currently no practically applicable method to easily measure absolute plasma or red cell volumes in a clinical setting. Here, a novel marker for plasma volume and red cell mass was developed through analysis of the observed variability caused by plasma volume shifts in common biochemical measures, selected based on their propensity to present with low variations over time. Once a month for 6 months, serum and whole blood samples were collected from 33 active males. Concurrently, the CO-rebreathing method was applied to determine target levels of hemoglobin mass (HbM) and blood volumes. The variability of 18 common chemistry markers and 27 Full Blood Count variables was investigated and matched to the observed plasma volume variation. After the removal of between-subject variations using a Bayesian model, multivariate analysis identified two sets of 8 and 15 biomarkers explaining 68% and 69% of plasma volume variance, respectively. The final multiparametric model contains a weighting function to allow for isolated abnormalities in single biomarkers. This proof-of-concept investigation describes a novel approach to estimate absolute vascular volumes, with a simple blood test. Despite the physiological instability of critically ill patients, it is hypothesized the model, with its multiparametric approach and weighting function, maintains the capacity to describe vascular volumes. This model has potential to transform volume management in clinical settings. Am. J. Hematol. 92:62-67, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Women with Red Hair Report A Slightly Increased Rate of Bruising, but Have Normal Coagulation Tests

PubMed Central

Liem, Edwin B.; Hollensead, Sandra C.; Joiner, Teresa V.

2005-01-01

There is an anecdotal impression that redheads experience more perioperative bleeding complications than those with other hair colors. We, therefore, tested the hypothesis that perceived problems with hemostasis could be detected with commonly used coagulation tests. Se studied healthy female Caucasian volunteers, 18 to 40 years, comparable in terms of height, weight, and age, with natural bright red (n = 25) or black or dark brown (n = 26) hair. Volunteers were questioned about their bleeding history and the following tests were performed: complete blood count, prothrombin time/international normalized ratio, activated partial thromboplastin time, platelet function analysis (PFA-100), and platelet aggregation using standard turbidimetric methodology. Agonists for aggregation were adenosine diphosphate, arachidonic acid, collagen, epinephrine, and two concentrations of ristocetin. The red-haired volunteers reported significantly more bruising, but there were no significant differences between the red- and dark-haired groups in hemoglobin concentration, platelet numbers, prothrombin time/international normalized ratio, or activated partial thromboplastin time. Furthermore, no significant differences in platelet function, as measured with the PFA-100 or with platelet aggregometry, were observed. We conclude that if redheads have hemostasis abnormalities, they are subtle. PMID:16368849

A theoretical model for optical oximetry at the capillary-level by optical coherence tomography (Conference Presentation)

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 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 red blood cells (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. Here we provide a theoretical model to calculate the backscattering spectra of single RBCs based on the first-order Born approximation, considering the orientation, size variation, and deformation of RBCs. 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 deformations of RBCs, allowing the sO2 of individual RBCs in capillaries to be characterized. The theoretical model is verified by Mie theory and experiments using visible light optical coherence tomography (vis-OCT). Thus, 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 by backscattering-based imaging modalities, challenging the popular view that such measurements are impossible at the single-capillary level. This is promising for in vivo backscattering-based optical oximetry at the single-capillary level, to measure local capillary sO2 for early diagnosis, progression monitoring, and treatment evaluation of diabetic retinopathy and cancer.

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

[Role of hemoglobin affinity to oxygen in adaptation to hypoxemia].

PubMed

Kwasiborski, Przemysław Jerzy; Kowalczyk, Paweł; Zieliński, Jakub; Przybylski, Jacek; Cwetsch, Andrzej

2010-04-01

One of the basic mechanisms of adapting to hypoxemia is a decrease in the affinity of hemoglobin for oxygen. This process occurs mainly due to the increased synthesis of 2,3-diphosphoglycerate (2,3-DPG) in the erythrocytes, as well as through the Bohr effect. Hemoglobin with decreased affinity for oxygen increases the oxygenation of tissues, because it gives up oxygen more easily during microcirculation. In foetal circulation, however, at a partial oxygen pressure (pO2) of 25 mmHg in the umbilical vein, the oxygen carrier is type F hemoglobin which has a high oxygen affinity. The commonly accepted role for hemoglobin F is limited to facilitating diffusion through the placenta. Is fetal life the only moment when haemoglobin F is useful? THE AIM OF STUDY was to create a mathematical model, which would answer the question at what conditions an increase, rather than a decrease, in haemoglobin oxygen affinity is of benefit to the body. Using the kinetics of dissociation of oxygen from hemoglobin described by the Hill equation as the basis for further discussion, we created a mathematical model describing the pO2 value in the microcirculatory system and its dependence on arterial blood pO2. The calculations were performed for hemoglobin with low oxygen affinity (adult type) and high-affinity hemoglobin (fetal type). The modelling took into account both physiological and pathological ranges of acid-base equilibrium and tissue oxygen extraction parameters. It was shown that for the physiological range of acid-base equilibrium and the resting level of tissue oxygen extraction parameters, with an arterial blood pO2 of 26.8 mmHg, the higher-affinity hemoglobin becomes the more effective oxygen carrier. It was also demonstrated that the arterial blood pO2, below which the high-affinity hemoglobin becomes the more effective carrier, is dependent on blood pH and the difference between the arterial and venous oxygen saturation levels. Simulations performed for the pathological states showed that acidosis and increased tissue oxygen demand lead to a broadened arterial blood pO2 range, in which the high-affinity hemoglobin is more efficient. Contrary to the widely held view that the only response to hypoxemia is a decrease in haemoglobin oxygen affinity, it was shown that under extreme hypoxemic conditions, an increased haemoglobin oxygen affinity improves the oxygenation of tissues. It was also shown that the dominance of hemoglobin with a high oxygen affinity rapidly exceeds hemoglobin with low oxygen affinity in the case of acidosis with its accompanying high tissue oxygen extraction. In cases of extreme disruptions of the acid-base equilibrium, the dominance of high-oxygen-affinity hemoglobin spans over the entire possible range of pO2 in arterial blood.

Hemoglobin thresholds and red blood cell transfusion in adult patients with moderate or severe traumatic brain injuries: A retrospective cohort study.

PubMed

Boutin, Amélie; Moore, Lynne; Green, Robert S; Zarychanski, Ryan; Erdogan, Mete; Lauzier, François; English, Shane; Fergusson, Dean A; Butler, Michael; McIntyre, Lauralyn; Chassé, Michaël; Lessard Bonaventure, Paule; Léger, Caroline; Desjardins, Philippe; Griesdale, Donald; Lacroix, Jacques; Turgeon, Alexis F

2018-06-01

We aimed to evaluate the association between transfusion practices and clinical outcomes in patients with traumatic brain injury. We conducted a retrospective cohort study of adult patients with moderate or severe traumatic brain injury admitted to the intensive care unit (ICU) of a level I trauma center between 2009 and 2013. The associations between hemoglobin (Hb) level, red blood cell (RBC) transfusion and clinical outcomes were estimated using robust Poisson models and proportional hazard models with time-dependent variables, adjusted for confounders. We included 215 patients. Sixty-six patients (30.7%) were transfused during ICU stay. The median pre-transfusion Hb among transfused patients was 81g/L (IQR 67-100), while median nadir Hb among non-transfused patients was 110g/L (IQR 93-123). Poor outcomes were significantly more frequent in patients who were transfused (mortality risk ratio [RR]: 2.15 [95% CI 1.37-3.38] and hazard ratio: 3.06 [95% CI 1.57-5.97]; neurological complications RR: 3.40 [95% CI 1.35-8.56]; trauma complications RR: 1.65 [95% CI 1.31-2.08]; ICU length of stay geometric mean ratio: 1.42 [95% CI 1.06-1.92]). During ICU stay, transfused patients tended to have lower Hb levels and worse outcomes than patients who did not receive RBCs, after adjustment for confounders. Copyright © 2017 Elsevier Inc. All rights reserved.

[Study on the interaction of hemoglobin and Cu(II)-ARS complex].

PubMed

Wu, Xiao-Hua; Miao, Ji-Gen; Miao, Yu-Qing; Chen, Jian-Rong

2007-06-01

The reaction of hemoglobin (Hb) with copper(II)-Alizarin red S (ARS) complex was studied in H3PO4-KH2PO4 buffer solution (pH 4. 2) by ultraviolet-visible spectrophotometry. The results show that the interaction of Hb and Cu(II)-ARS complex produces red ionic association complex with its maximum absorption peak at 537 nm. At the maximum absorption, the composition of the complex was determined to be n(Hb) : n(Cu(II)) : n(ARS) =1 : 4 : 8, and the apparent molar absorptivity was 1.52 x 10(5) L x mol(-1) x cm(-1). The concentration of Hb is linear with the absorbency in the range of 1.0 x 10(-7)-2.0 x 10(-6) mol x L(-1) and the regression equation was established as A = 0.026 9 + 151 675c (mol x L(-1)) with the coefficient r = 0.997 2. The effects of solution acidity, reagent amount, reaction time, temperature, ionic strength and the added surfactant were examined on the formation of the Hb-Cu(II)-ARS complex. A preliminary investigation was carried out to elucidate the reaction mechanism, and it could be concluded that the Hb and Cu(II)-ARS complex are combined mainly by electrostatic attraction. Further investigation was also undertaken to find out the effects of common amino acids and metallic ions on the formation of Hb-Cu(II)-ARS complex.

A simple biofuel cell cathode with human red blood cells as electrocatalysts for oxygen reduction reaction.

PubMed

Ayato, Yusuke; Sakurai, Kenichiro; Fukunaga, Saori; Suganuma, Takuya; Yamagiwa, Kiyofumi; Shiroishi, Hidenobu; Kuwano, Jun

2014-05-15

A red blood cell (RBC) from human exhibited direct electron transfer (DET) activity on a bare indium tin oxide (ITO) electrode. A formal potential of -0.152 V vs. a silver-silver chloride saturated potassium chloride (Ag|AgCl|KCl(satd.)) was estimated for the human RBC (type AB) from a pair of redox peaks at around 0.089 and -0.215 V (vs. Ag|AgCl|KCl(satd.)) on cyclic voltammetric (CV) measurements in a phosphate buffered saline (PBS; 39 mM; pH 7.4) solution. The results agreed well with those of a redox couple for iron-bearing heme groups in hemoglobin molecules (HbFe(II)/HbFe(III)) on the bare ITO electrodes, indicated that DET active species were hemoglobin (Hb) molecules encapsulated by a phospholipid bilayer membrane of the human RBC. The quantity of electrochemically active Hb in the human RBC was estimated to be 30 pmol cm(-2). In addition, the human RBC exhibited oxygen reduction reaction (ORR) activity in the dioxygen (O2) saturated PBS solution at the negative potential from ca. -0.15 V (vs. Ag|AgCl|KCl(satd.)). A single cell test proved that a biofuel cell (BFC) with an O2|RBC|ITO cathode showed the open-circuit voltage (OCV) of ca. 0.43 V and the maximum power density of ca. 0.68 μW cm(-2). © 2013 Published by Elsevier B.V.

Measuring osmosis and hemolysis of red blood cells.

PubMed

Goodhead, Lauren K; MacMillan, Frances M

2017-06-01

Since the discovery of the composition and structure of the mammalian cell membrane, biologists have had a clearer understanding of how substances enter and exit the cell's interior. The selectively permeable nature of the cell membrane allows the movement of some solutes and prevents the movement of others. This has important consequences for cell volume and the integrity of the cell and, as a result, is of utmost clinical importance, for example in the administration of isotonic intravenous infusions. The concepts of osmolarity and tonicity are often confused by students as impermeant isosmotic solutes such as NaCl are also isotonic; however, isosmotic solutes such as urea are actually hypotonic due to the permeant nature of the membrane. By placing red blood cells in solutions of differing osmolarities and tonicities, this experiment demonstrates the effects of osmosis and the resultant changes in cell volume. Using hemoglobin standard solutions, where known concentrations of hemoglobin are produced, the proportion of hemolysis and the effect of this on resultant hematocrit can be estimated. No change in cell volume occurs in isotonic NaCl, and, by placing blood cells in hypotonic NaCl, incomplete hemolysis occurs. By changing the bathing solution to either distilled water or isosmotic urea, complete hemolysis occurs due to their hypotonic effects. With the use of animal blood in this practical, students gain useful experience in handling tissue fluids and calculating dilutions and can appreciate the science behind clinical scenarios. Copyright © 2017 the American Physiological Society.

Hemoglobin redox reactions and red blood cell aging.

PubMed

Rifkind, Joseph M; Nagababu, Enika

2013-06-10

The physiological mechanism(s) for recognition and removal of red blood cells (RBCs) from circulation after 120 days of its lifespan is not fully understood. Many of the processes thought to be associated with the removal of RBCs involve oxidative stress. We have focused on hemoglobin (Hb) redox reactions, which is the major source of RBC oxidative stress. The importance of Hb redox reactions have been shown to originate in large parts from the continuous slow autoxidation of Hb producing superoxide and its dramatic increase under hypoxic conditions. In addition, oxidative stress has been shown to be associated with redox reactions that originate from Hb reactions with nitrite and nitric oxide (NO) and the resultant formation of highly toxic peroxynitrite when NO reacts with superoxide released during Hb autoxidation. The interaction of Hb, particularly under hypoxic conditions with band 3 of the RBC membrane is critical for the generating the RBC membrane changes that trigger the removal of cells from circulation. These changes include exposure of antigenic sites, increased calcium leakage into the RBC, and the resultant leakage of potassium out of the RBC causing cell shrinkage and impaired deformability. The need to understand the oxidative damage to specific membrane proteins that result from redox reactions occurring when Hb is bound to the membrane. Proteomic studies that can pinpoint the specific proteins damaged under different conditions will help elucidate the cellular aging processes that result in cells being removed from circulation.

Biochemical and hematological effects of lead ingestion in nestling American kestrels (Falco sparverius)

USGS Publications Warehouse

Hoffman, D.J.; Franson, J.C.; Pattee, O.H.; Bunck, C.M.; Murray, H.C.

1985-01-01

1. One-day old American kestrel (Faico sparverius) nestlings were orally dosed daily with 5 μl/g of corn oil (controls), 25, 125 or 625 mg/kg of metallic lead in corn oil for 10 days.2. Forty per cent of the nestlings receiving 625 mg/kg of lead died after 6 days and growth rates were significantly depressed in the two highest lead dosed groups. At 10 days hematocrit values were significantly lower in the two highest lead treated groups, and hemoglobin content and red blood cell (δ-aminolevulinic acid dehydratase (ALAD) activity was depressed in all lead treated groups. Plasma creatine phosphokinase decreased in the two highest treatment groups.3. Brain, liver and kidney ALAD activities, brain RNA to protein ratio and liver protein concentration decreased after lead exposure whereas liver DNA, DNA to RNA ratio and DNA to protein ratio increased. Brain monoamine oxidase and ATPase were not significantly altered.4. Measurements of the ontogeny of hematological variants and enzymes in normal development, using additional untreated nestlings, revealed decreases in red blood cell ALAD, plasma aspartate amino transferase, lactate dehydrogenase, brain DNA and RNA and liver DNA, whereas hematocrit, hemoglobin, plasma alkaline phosphatase, brain monoamine oxidase, brain ALAD and liver ALAD increased during the first 10 days of posthatching development.5. Biochemical and hematological alterations were more severe than those reported in adult kestrels or precocial young birds exposed to lead. Alterations may be due in part to delayed development.

Assessment of Wearable Technology for Integrated Decision Support

DTIC Science & Technology

2016-05-01

absorption of red  light by oxygen‐bound (or unbound)  hemoglobin   in the blood (see figure 9).  The measurement  is achieved by  shining both  red  light...Leadership  &  Education , Personnel, and Facilities (DOTMLPF) assessment. There may, however, be a clear  value  in keeping these decision support tools closer...Soldier mission sets.  The “Signature TrRacking for Optimized  Nutrition  and traininG” (STRONG) Lab at Air Force Research Labs at Wright Patterson Air

In vitro optical detection of simulated blood pulse in a human tooth pulp model.

PubMed

Niklas, A; Hiller, K-A; Jaeger, A; Brandt, M; Putzger, J; Ermer, C; Schulz, I; Monkman, G; Giglberger, S; Hirmer, M; Danilov, S; Ganichev, S; Schmalz, G

2014-01-01

Noninvasive optical methods such as photoplethysmography, established for blood pulse detection in organs, have been proposed for vitality testing of human dental pulp. However, no information is available on the mechanism of action in a closed pulp chamber and on the impairing influence of other than pulpal blood flow sources. Therefore, the aim of the present in vitro study was to develop a device for the optical detection of pulpal blood pulse and to investigate the influence of different parameters (including gingival blood flow [GBF] simulation) on the derived signals. Air, Millipore water, human erythrocyte suspensions (HES), non-particulate hemoglobin suspension (NPHS), and lysed hemoglobin suspension (LHES) were pulsed through a flexible (silicone) or a rigid (glass) tube placed within an extracted human molar in a tooth-gingiva model. HES was additionally pulsed through a rigid tube around the tooth, simulating GBF alone or combined with the flow through the tooth by two separate peristaltic pumps. Light from high-power light-emitting diodes (625 nm (red) and 940 nm (infrared [IR]); Golden Dragon, Osram, Germany) was introduced to the coronal/buccal part of the tooth, and the signal amplitude [∆U, in volts] of transmitted light was detected by a sensor at the opposite side of the tooth. Signal processing was carried out by means of a newly developed blood pulse detector. Finally, experiments were repeated with the application of rubber dam (blue, purple, pink, and black), aluminum foil, and black antistatic plastic foil. Nonparametric statistical analysis was applied (n = 5; α = 0.05). Signals were obtained for HES and LHES, but not with air, Millipore water, or NPHS. Using a flexible tube, signals for HES were higher for IR compared to red light, whereas for the rigid tube, the signals were significantly higher for red light than for IR. In general, significantly less signal amplitude was recorded for HES with the rigid glass tube than with the flexible tube, but it was still enough to be detected. ∆U from gingiva compared to tooth was significantly lower for red light and higher for IR. Shielding the gingiva was effective for 940 nm light and negligible for 625 nm light. Pulpal blood pulse can be optically detected in a rigid environment such as a pulp chamber, but GBF may interfere with the signal and the shielding effect of the rubber dam depends on the light wavelength used. The optically based recording of blood pulse may be a suitable method for pulp vitality testing, if improvements in the differentiation between different sources of blood pulse are possible.

Hypergravity-Induced Changes in Hematological and Lymphocyte Function Parameters in a Mouse Model

NASA Technical Reports Server (NTRS)

Gridley, Daila S.; Miller, Glen M.; Nelson, Gregory A.; Pecaut, Michael J.

2003-01-01

The purpose of this study was to quantify hypergravity-induced changes in hematological and lymphocyte characteristics. Mice were subjected to 1, 2, and 3G and euthanized on days 1 , 4, 7, 10, and 21. The data show that increased gravitational force resulted in persistent hypothermia. Red blood cell (RBC) counts, hematocrit, and hemoglobin were reduced by day 21, whereas hemoglobin and RBC volume were low at most times of measurement. A transient increase was noted in platelet numbers in the 3G group. Fluctuations in spontaneous blastogenesis of lymphocytes were dependent upon centrifugation time and not gravity. Changes in splenocyte responses to T and B cell mitogens due to gravity were also noted. Cytokine production was primarily affected during the first week; IL-2, IL-4 and TNF-alpha were increased, whereas IFN-gamma was decreased. These findings indicate that altered gravity can influence both hematological and functional variables that may translate into serious health consequences.

Nonpharmacological, Blood Conservation Techniques for Preventing Neonatal Anemia—Effective and Promising Strategies for Reducing Transfusion

PubMed Central

Carroll, Patrick D.; Widness, John A.

2012-01-01

The development of anemia after birth in very premature, critically ill newborn infants is a universal well-described phenomenon. Although preventing anemia in this population, along with efforts to establish optimal red blood cell (RBC) transfusion and pharmacologic therapy continue to be actively investigated, the present review focuses exclusively on nonpharmacological approaches to the prevention and treatment of neonatal anemia. We begin with an overview of topics relevant to nonpharmacological techniques. These topics include neonatal and fetoplacental hemoglobin levels and blood volumes, clinical and laboratory practices applied in critically ill neonates, and current RBC transfusion practice guidelines. This is followed by a discussion of the most effective and promising nonpharmacological blood conservation strategies and techniques. Fortunately, many of these techniques are feasible in most neonatal intensive care units. When applied together, these techniques are more effective than existing pharmacotherapies in significantly decreasing neonatal RBC transfusions. They include increasing hemoglobin endowment and circulating blood volume at birth; removing less blood for laboratory testing; and optimizing nutrition. PMID:22818543

Preparation and characterization of hemoglobin-silver composites as biocompatible antiseptics.

PubMed

Li, Peiyuan; Tong, Zhangfa; Jia, Zhiruo; Su, Wei

2016-11-01

Microbial contamination has been a major challenge in a wide variety of fields such as biomedical and biomaterial applications. The development of biomaterials that possess excellent antibacterial ability and biocompatibility is of great importance to enhance the service life of biomaterials. In this study, the main protein component of red blood cells, hemoglobin (Hb), was employed to prepare Ag-Hb nanocomposites as novel biocompatible antiseptics. The formation of Ag-Hb nanocomposites on the titanium substrate are confirmed by field-emission scanning electron microscopy, Fourier transformed infrared spectroscopic, contact angles, and inductively coupled plasma atomic emission spectrometry analysis. The Ag-Hb titanium shows potent antibacterial ability against planktonic bacteria in the suspension and ability to prevent bacterial adhesion. Moreover, the Ag-Hb titanium shows excellent biocompatibility, which supports healthy osteoblast cellular activity and osteoblast differentiation. The results indicate that the Ag-Hb nanocomposites can be potentially useful for the fabrication of biomaterials for long-term applications. © The Author(s) 2016.

Comparison of immunohematological profile between endurance- and power-oriented elite athletes.

PubMed

Morgado, José P; Matias, Catarina N; Monteiro, Cristina P; Alves, Francisco; Reis, Joana F; Santos, Diana A; Silva, Analiza M; Martins, Fátima; Seixas, Maria T; Rocha-Pereira, Petronila; Sardinha, Luís B; Laires, Maria J

2017-03-01

There is general perception that elite athletes are highly susceptible to changes in immunohematological profile. The objective of this study was to compare immunohematological parameters of elite athletes of different aerobic and muscular strength sports and analyze changes over 2 months. Sixteen judoists and 14 swimmers were evaluated 2 months before (M1) and immediately prior to competition (M2). Hemogram and lymphocytes subpopulations were assessed with automatic counter and flow cytometry, respectively. Judoists had higher neutrophils and lower monocytes and eosinophils percentages than swimmers at M1 and M2. At M2 judoists had lower red blood cells (RBC), hemoglobin, and hematocrit than swimmers. At M2 judoists' hematocrit and CD16 decreased while swimmers' hemoglobin and hematocrit increased. In conclusion, neither sports characteristics nor intense training seem to displace the athletes' immunohematological profile out of the clinical range, despite the possibility of occurrence of microlesions that may stimulate production of leukocytes and reduction of RBC in judoists.

Neocytolysis on descent from altitude: a newly recognized mechanism for the control of red cell mass

NASA Technical Reports Server (NTRS)

Rice, L.; Ruiz, W.; Driscoll, T.; Whitley, C. E.; Tapia, R.; Hachey, D. L.; Gonzales, G. F.; Alfrey, C. P.

2001-01-01

BACKGROUND: Studies of space-flight anemia have uncovered a physiologic process, neocytolysis, by which young red blood cells are selectively hemolyzed, allowing rapid adaptation when red cell mass is excessive for a new environment. OBJECTIVES: 1) To confirm that neocytolysis occurs in another situation of acute plethora-when high-altitude dwellers with polycythemia descend to sea level; and 2) to clarify the role of erythropoietin suppression. DESIGN: Prospective observational and interventional study. SETTING: Cerro de Pasco (4380 m) and Lima (sea level), Peru. PARTICIPANTS: Nine volunteers with polycythemia. INTERVENTIONS: Volunteers were transported to sea level; three received low-dose erythropoietin. MEASUREMENTS: Changes in red cell mass, hematocrit, hemoglobin concentration, reticulocyte count, ferritin level, serum erythropoietin, and enrichment of administered(13)C in heme. RESULTS: In six participants, red cell mass decreased by 7% to 10% within a few days of descent; this decrease was mirrored by a rapid increase in serum ferritin level. Reticulocyte production did not decrease, a finding that establishes a hemolytic mechanism.(13)C changes in circulating heme were consistent with hemolysis of young cells. Erythropoietin was suppressed, and administration of exogenous erythropoietin prevented the changes in red cell mass, serum ferritin level, and(13)C-heme. CONCLUSIONS: Neocytolysis and the role of erythropoietin are confirmed in persons with polycythemia who descend from high altitude. This may have implications that extend beyond space and altitude medicine to renal disease and other situations of erythropoietin suppression, hemolysis, and polycythemia.

Red-light excitation of protoporphyrin IX fluorescence for subsurface tumor detection.

PubMed

Roberts, David W; Olson, Jonathan D; Evans, Linton T; Kolste, Kolbein K; Kanick, Stephen C; Fan, Xiaoyao; Bravo, Jaime J; Wilson, Brian C; Leblond, Frederic; Marois, Mikael; Paulsen, Keith D

2018-06-01

OBJECTIVE The objective of this study was to detect 5-aminolevulinic acid (ALA)-induced tumor fluorescence from glioma below the surface of the surgical field by using red-light illumination. METHODS To overcome the shallow tissue penetration of blue light, which maximally excites the ALA-induced fluorophore protoporphyrin IX (PpIX) but is also strongly absorbed by hemoglobin and oxyhemoglobin, a system was developed to illuminate the surgical field with red light (620-640 nm) matching a secondary, smaller absorption peak of PpIX and detecting the fluorescence emission through a 650-nm longpass filter. This wide-field spectroscopic imaging system was used in conjunction with conventional blue-light fluorescence for comparison in 29 patients undergoing craniotomy for resection of high-grade glioma, low-grade glioma, meningioma, or metastasis. RESULTS Although, as expected, red-light excitation is less sensitive to PpIX in exposed tumor, it did reveal tumor at a depth up to 5 mm below the resection bed in 22 of 24 patients who also exhibited PpIX fluorescence under blue-light excitation during the course of surgery. CONCLUSIONS Red-light excitation of tumor-associated PpIX fluorescence below the surface of the surgical field can be achieved intraoperatively and enables detection of subsurface tumor that is not visualized under conventional blue-light excitation. Clinical trial registration no.: NCT02191488 (clinicaltrials.gov).

Characterizations of individual human red blood cells from patients with diabetes mellitus (Conference Presentation)

NASA Astrophysics Data System (ADS)

Lee, SangYun; Jang, Seongsoo; Park, HyunJoo; Park, YongKeun

2016-03-01

We systematically measure the morphological, biochemical, and biomechanical properties of individual human red blood cells (RBCs) from patients with diabetes mellitus using quantitative phase imaging technique to characterize the diabetic red cells with respect to those of the healthy. The 3-D refractive index tomograms and 2-D dynamic membrane fluctuation maps of individual RBCs are reconstructed from a set of the retrieved complex optical fields at various laser incidence angles using the Common-path diffraction optical tomography, from which volume, surface area, sphericity, hemoglobin (Hb) concentration, Hb content, and membrane fluctuation are obtained simultaneously. The correlative relations among the retrieved red cell indices of diabetic and healthy RBCs are also investigated with capabilities of individual cell measurement. As expected, there are no significant alterations in morphologies (cellular volumes, surface area, and sphericity) between diabetic and healthy RBCs. However, despite the minute mean corpuscular Hb differences in cell blood count datasheet, the measured Hb concentrations and Hb contents of diabetic RBCs are statistically higher than those of healthy RBCs, which might be related to the glycation of Hb molecules by hyperglycemia. Meanwhile, the membrane fluctuations of diabetic RBCs are clearly diminished compared to healthy red cells, implying the significantly decreased RBC deformability. In particular, it seems that the membrane fluctuations have mild negative relationships with the reported HbA1c levels.

Clinical Course of Homozygous Hemoglobin Constant Spring in Pediatric Patients.

PubMed

Komvilaisak, Patcharee; Jetsrisuparb, Arunee; Fucharoen, Goonnapa; Komwilaisak, Ratana; Jirapradittha, Junya; Kiatchoosakun, Pakaphan

2018-04-17

Hemoglobin (Hb) Constant Spring is an alpha-globin gene variant due to a mutation of the stop codon resulting in the elongation of the encoded polypeptide from 141 to 172 amino acid residues. Patients with homozygous Hb Constant Spring are usually mildly anemic. We retrospectively describe clinical manifestations, diagnosis, laboratory investigations, treatment, and associated findings in pediatric patients with homozygous Hb Constant Spring followed-up at Srinagarind Hospital. Sixteen pediatric cases (5 males and 11 females) were diagnosed in utero (N=6) or postnatal (n=10). Eleven cases were diagnosed with homozygous Hb Constant Spring, 4 with homozygous Hb Constant Spring with heterozygous Hb E, and 1 with homozygous Hb Constant Spring with homozygous Hb E. Three cases were delivered preterm. Six patients had low birth weights. Clinical manifestations included fetal anemia in 6 cases, hepatomegaly in 1 case, hepatosplenomegaly in 2 cases, splenomegaly in 1 case. Twelve cases exhibited early neonatal jaundice, 9 of which required phototherapy. Six cases received red cell transfusions; 1 (3), >1 (3). After the first few months of life, almost all patients had mild microcytic hypochromic anemia and an increased reticulocyte count with a wide red cell distribution (RDW), but no longer required red cell transfusion. At 1 to 2 years of age, some patients still had mild microcytic hypochromic anemia and some had normocytic hypochromic anemia with Hb around 10 g/dL, increased reticulocyte count and wide RDW. Associated findings included hypothyroidism (2), congenital heart diseases (4), genitourinary abnormalities (3), gastrointestinal abnormalities (2), and developmental delay (1). Pediatric patients with homozygous Hb Constant Spring developed severe anemia in utero and up to the age of 2 to 3 months postnatal, requiring blood transfusions. Subsequently, their anemia was mild with no evidence of hepatosplenomegaly. Their Hb level was above 9 g/dL with hypochromic microcytic blood pictures as well as wide RDW. Blood transfusions have not been necessary since then.

Tract specific analysis in patients with sickle cell disease

NASA Astrophysics Data System (ADS)

Chai, Yaqiong; Coloigner, Julie; Qu, Xiaoping; Choi, Soyoung; Bush, Adam; Borzage, Matt; Vu, Chau; Lepore, Natasha; Wood, John

2015-12-01

Sickle cell disease (SCD) is a hereditary blood disorder in which the oxygen-carrying hemoglobin molecule in red blood cells is abnormal. It affects numerous people in the world and leads to a shorter life span, pain, anemia, serious infections and neurocognitive decline. Tract-Specific Analysis (TSA) is a statistical method to evaluate white matter alterations due to neurocognitive diseases, using diffusion tensor magnetic resonance images. Here, for the first time, TSA is used to compare 11 major brain white matter (WM) tracts between SCD patients and age-matched healthy subjects. Alterations are found in the corpus callosum (CC), the cortico-spinal tract (CST), inferior fronto-occipital fasciculus (IFO), inferior longitudinal fasciculus (ILF), superior longitudinal fasciculus (SLF), and uncinated fasciculus (UNC). Based on previous studies on the neurocognitive functions of these tracts, the significant areas found in this paper might be related to several cognitive impairments and depression, both of which are observed in SCD patients.

Microscopic or occult hematuria, when reflex testing is not good laboratory practice.

PubMed

Froom, Paul; Barak, Mira

2010-01-01

Consensus opinion suggests that hematuria found by dipstick and not confirmed on microscopic examination (<2 erythrocytes per high power field) signifies a false-positive reagent strip test result. Standard practice is to repeat the dipstick test several days later and if still positive to confirm by microscopic examination. If discordant results are obtained, experts recommend reflex testing for urinary myoglobin and hemoglobin concentrations. The question is whether or not this approach represents good laboratory practice. These recommendations are not evidence based. We conclude that the reference range for red blood cells on the reagent strip should be increased to 25x10(6) cells/L for young men, and 50x10(6) cells/L for the rest of the adult population, ranges consistent with flow cytometry reports. Confirmation reflex testing using tests that have inferior sensitivity, precision and probably accuracy is not recommended.

Comparative In Vivo Effects of Hemoglobin-Based Oxygen Carriers (HBOC) with Varying Prooxidant and Physiological Reactivity.

PubMed

Toma, Vlad Al; Farcaș, Anca D; Roman, Ioana; Sevastre, Bogdan; Hathazi, Denisa; Scurtu, Florina; Damian, Grigore; Silaghi-Dumitrescu, Radu

2016-01-01

A series of hemoglobin-based oxygen carrier candidates (HBOC), previously noted for their differences in prooxidative and physiological reactivity, were compared in terms of the negative effects displayed upon injection in Wistar rats. At the concentrations tested, antioxidant strategies based on albumin as well as based on rubrerythrin appear to offer observable physiological advantages.

A computational model of oxygen delivery by hemoglobin-based oxygen carriers in three-dimensional microvascular networks.

PubMed

Tsoukias, Nikolaos M; Goldman, Daniel; Vadapalli, Arjun; Pittman, Roland N; Popel, Aleksander S

2007-10-21

A detailed computational model is developed to simulate oxygen transport from a three-dimensional (3D) microvascular network to the surrounding tissue in the presence of hemoglobin-based oxygen carriers. The model accounts for nonlinear O(2) consumption, myoglobin-facilitated diffusion and nonlinear oxyhemoglobin dissociation in the RBCs and plasma. It also includes a detailed description of intravascular resistance to O(2) transport and is capable of incorporating realistic 3D microvascular network geometries. Simulations in this study were performed using a computer-generated microvascular architecture that mimics morphometric parameters for the hamster cheek pouch retractor muscle. Theoretical results are presented next to corresponding experimental data. Phosphorescence quenching microscopy provided PO(2) measurements at the arteriolar and venular ends of capillaries in the hamster retractor muscle before and after isovolemic hemodilution with three different hemodilutents: a non-oxygen-carrying plasma expander and two hemoglobin solutions with different oxygen affinities. Sample results in a microvascular network show an enhancement of diffusive shunting between arterioles, venules and capillaries and a decrease in hemoglobin's effectiveness for tissue oxygenation when its affinity for O(2) is decreased. Model simulations suggest that microvascular network anatomy can affect the optimal hemoglobin affinity for reducing tissue hypoxia. O(2) transport simulations in realistic representations of microvascular networks should provide a theoretical framework for choosing optimal parameter values in the development of hemoglobin-based blood substitutes.

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.

Affinity of hemoglobin for the cytoplasmic fragment of human erythrocyte membrane band 3. Equilibrium measurements at physiological pH using matrix-bound proteins: the effects of ionic strength, deoxygenation and of 2,3-diphosphoglycerate.

PubMed

Chétrite, G; Cassoly, R

1985-10-05

The cytoplasmic fragment of band 3 protein isolated from the human erythrocyte membrane was linked to a CNBr-activated Sepharose matrix in an attempt to measure, in batch experiments, its equilibrium binding constant with oxy- and deoxyhemoglobin at physiological pH and ionic strength values and in the presence or the absence of 2,3-diphosphoglycerate. All the experiments were done at pH 7.2, and equilibrium constants were computed on the basis of one hemoglobin tetramer bound per monomer of fragment. In 10 mM-phosphate buffer, a dissociation constant KD = 2 X 10(-4)M was measured for oxyhemoglobin and was shown to increase to 8 X 10(-4)M in the presence of 50 mM-NaCl. Association could not be demonstrated at higher salt concentrations. Diphosphoglycerate-stripped deoxyhemoglobin was shown to associate more strongly with the cytoplasmic fragment of band 3. In 10 mM-bis-Tris (pH 7.2) and in the presence of 120 mM-NaCl, a dissociation constant KD = 4 X 10(-4)M was measured. Upon addition of increasing amounts of 2,3-diphosphoglycerate, the complex formed between deoxyhemoglobin and the cytoplasmic fragment of band 3 was dissociated. On the reasonable assumption that the hemoglobin binding site present on band 3 fragment was not modified upon linking the protein to the Sepharose matrix, the results indicated that diphosphoglycerate-stripped deoxyhemoglobin or partially liganded hemoglobin tetramers in the T state could bind band 3 inside the intact human red blood cell.

Targetting the hemozoin synthesis pathway for antimalarial drug and detected by TEM (Transmission electron microscope)

NASA Astrophysics Data System (ADS)

Abbas, Jamilah; Artanti, Nina; Sundowo, Andini; Dewijanti, Indah Dwiatmi; Hanafi, Muhammad; Lisa, Syafrudin, Din

2017-11-01

Malaria is a major public health problem mainly due to the development of resistance by the most lethal causative parasite species, the alarming spread of drug resistance and limited number of effective drug available now. Therefore it is important to discover new antimalarial drug. Malaria is caused by a singlecelled parasite from the genus Plasmodium. Plasmodium falciparum parasite infect red blood cells, ingesting and degradation hemoglobin in the acidic food vacuola trough a sequential metabolic process involving multiple proteases. During these process, hemoglobin is utilized as the predominant source of nutrition. Proteolysis of hemoglobin yields amino acid for protein synthesis as well as toxic heme. Massive degradation of hemoglobin generates large amount of toxic heme. Malaria parasite has evolved a distinct mechanism for detoxification of heme through conversion into insoluble crystalline pigment, known as hemozoin (β hematoin). Hemozoin synthesis is an indispensable process for the parasite and is the target for action of several known antimalarial drug. TEM (Transmission Electron Microscope) technology for hemozoin formation in vitro assay was done in this research. Calophyllum aerophyllum Lauterb as medicinal plants was used as a source of antimalarial drug. Acetone extracts of C. lowii showed growth inhibition against parasite P. falciparum with IC50 = 5.2 µg/mL. Whereas from hexane, acetone and methanol fraction of C. aerophyllum showed growth inhibition with IC50 = 0.054, 0.055 and 0.0054 µg/mL respectively. New drug from Calophyllum might have potential compounds that have unique structures and mechanism of action which required to develop new drug for treatment of sensitive and drug resistant strain of malaria.

Effect of Repeated Whole Blood Donations on Aerobic Capacity and Hemoglobin Mass in Moderately Trained Male Subjects: A Randomized Controlled Trial.

PubMed

Meurrens, Julie; Steiner, Thomas; Ponette, Jonathan; Janssen, Hans Antonius; Ramaekers, Monique; Wehrlin, Jon Peter; Vandekerckhove, Philippe; Deldicque, Louise

2016-12-01

The aims of the present study were to investigate the impact of three whole blood donations on endurance capacity and hematological parameters and to determine the duration to fully recover initial endurance capacity and hematological parameters after each donation. Twenty-four moderately trained subjects were randomly divided in a donation (n = 16) and a placebo (n = 8) group. Each of the three donations was interspersed by 3 months, and the recovery of endurance capacity and hematological parameters was monitored up to 1 month after donation. Maximal power output, peak oxygen consumption, and hemoglobin mass decreased (p < 0.001) up to 4 weeks after a single blood donation with a maximal decrease of 4, 10, and 7%, respectively. Hematocrit, hemoglobin concentration, ferritin, and red blood cell count (RBC), all key hematological parameters for oxygen transport, were lowered by a single donation (p < 0.001) and cumulatively further affected by the repetition of the donations (p < 0.001). The maximal decrease after a blood donation was 11% for hematocrit, 10% for hemoglobin concentration, 50% for ferritin, and 12% for RBC (p < 0.001). Maximal power output cumulatively increased in the placebo group as the maximal exercise tests were repeated (p < 0.001), which indicates positive training adaptations. This increase in maximal power output over the whole duration of the study was not observed in the donation group. Maximal, but not submaximal, endurance capacity was altered after blood donation in moderately trained people and the expected increase in capacity after multiple maximal exercise tests was not present when repeating whole blood donations.

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.

A rare case of a three way complex variant positive Philadelphia translocation involving chromosome (9;11;22)(q34;p15;q11) in chronic myeloid leukemia: A case report

PubMed Central

Asif, Muhammad; Hussain, Abrar; Rasool, Mahmood

2016-01-01

The t(9;22)(q34;q11) translocation is present in 90–95% of patients with chronic myeloid leukemia (CML). Variant complex translocations have been observed in 5–8% of CML patients, in which a third chromosome other than (9;22) is involved. Imatinib mesylate is the first line breakpoint cluster region-Abelson gene (BCR/ABL)-targeted oral therapy for CML, and may produce a complete response in 70–80% of CML patients in the chronic phase. In the present study, a bone marrow sample was used for conventional cytogenetic analysis, and the fluorescence in situ hybridization (FISH) test was used for BCR/ABL gene detection. A hematological analysis was also performed to determine the white blood cell (WBC) count, red blood cell count, hemoglobin levels, packed and mean cell volumes, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration and platelet values of the patient. The hematological analysis of the patient indicated the increased WBC of 186.5×103 cells/µl, and decreased hemoglobin levels of 11.1 g/dl. The FISH test revealed that 67% cells demonstrated BCR/ABL gene translocation. The patient was treated with 400 mg imatinib mesylate daily, and was monitored at various intervals over a 6-month period. The present study reports the rare case of a patient that demonstrates a three-way Philadelphia chromosome-positive translocation involving 46XY,t(9;11;22)(q34;p15;q11)[10], alongside CML in the chronic phase. The translocation was analyzed using cytogenetic and FISH tests. PMID:27602125

Blood flow estimation in gastroscopic true-color images

NASA Astrophysics Data System (ADS)

Jacoby, Raffael S.; Herpers, Rainer; Zwiebel, Franz M.; Englmeier, Karl-Hans

1995-05-01

The assessment of blood flow in the gastrointestinal mucosa might be an important factor for the diagnosis and treatment of several diseases such as ulcers, gastritis, colitis, or early cancer. The quantity of blood flow is roughly estimated by computing the spatial hemoglobin distribution in the mucosa. The presented method enables a practical realization by calculating approximately the hemoglobin concentration based on a spectrophotometric analysis of endoscopic true-color images, which are recorded during routine examinations. A system model based on the reflectance spectroscopic law of Kubelka-Munk is derived which enables an estimation of the hemoglobin concentration by means of the color values of the images. Additionally, a transformation of the color values is developed in order to improve the luminance independence. Applying this transformation and estimating the hemoglobin concentration for each pixel of interest, the hemoglobin distribution can be computed. The obtained results are mostly independent of luminance. An initial validation of the presented method is performed by a quantitative estimation of the reproducibility.

A Molecular Dynamic Modeling of Hemoglobin-Hemoglobin Interactions

NASA Astrophysics Data System (ADS)

Wu, Tao; Yang, Ye; Sheldon Wang, X.; Cohen, Barry; Ge, Hongya

2010-05-01

In this paper, we present a study of hemoglobin-hemoglobin interaction with model reduction methods. We begin with a simple spring-mass system with given parameters (mass and stiffness). With this known system, we compare the mode superposition method with Singular Value Decomposition (SVD) based Principal Component Analysis (PCA). Through PCA we are able to recover the principal direction of this system, namely the model direction. This model direction will be matched with the eigenvector derived from mode superposition analysis. The same technique will be implemented in a much more complicated hemoglobin-hemoglobin molecule interaction model, in which thousands of atoms in hemoglobin molecules are coupled with tens of thousands of T3 water molecule models. In this model, complex inter-atomic and inter-molecular potentials are replaced by nonlinear springs. We employ the same method to get the most significant modes and their frequencies of this complex dynamical system. More complex physical phenomena can then be further studied by these coarse grained models.