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.

[Cardiac manifestations of sickle cell anemia].

PubMed

Gacon, P H; Donatien, Y

HEMOGLOBINS S AND C: Drepanocytosis, the occurrence of sickle cells (drepanocytes) in the blood, is an inherited condition. Electrophoresis demonstrates hemoglobin SS in homozygous subjects who present the typical clinical features of severe hemolytic sickle-cell anemia. Heterozygous subjects have sickle-cell anemia trait, an asymptomatic condition associated with a 50% hemoglobin S and 50% hemoglobin C at electrophoresis. Hemoglobin S and C are transmitted by Mendelian inheritance. CARDIAC DISORDERS: Well-known, cardiac disorders occur in more than 82% of homozygous subjects while only 2% of heterozygous subjects are affected. Heart murmur, radiological cardiomegaly, or eletrocardiographic anomalies are often the only signs. There is a risk of fatal heart failure in children and neonates. Acute rheumatic fever or infectious endocarditis, particularly due to pneumococcal or Haemophilus influenzae infection, may trigger heart failure. CARDIAC ANOMALIES: Patients with sickle-cell anemia can develop an "anemic heart" expressed by an elevated cardiac output and systemic ejection volume at rest and a fall in arteriolar peripheral resistance. Patients who develop cor pulmonae have an elevated pulmonary pressure at exercise and experience venous occlusive events with a progressive reduction in the pulmonary vascular bed and development of a left-right shunt. Myocardiopathy leads to left ventricular dysfunction contrasting with the dilated right heart seen at echocardiography and rare cases of transmural infarction.

Artificial Cells, Blood Substitutes, and Immobilization Biotechnology. Volume 22, Number 3, 1994.

DTIC Science & Technology

1994-05-01

culture, microorganisms, enzymes, drugs, receptors, sorbents, immunosorbents and other biologically active molecules. (2) Artificial cells, microcapsules ...recombinant hemoglobin, and others. Chemistry, methods, in-vitro studies, in-vivo evaluations and clinical results. (4) Microencapsulation and other

Artificial Cells, Blood Substitutes, and Immobilization Biotechnology. Volume 22 Number 2, 1994.

DTIC Science & Technology

1994-05-01

culture, microorganisms, enzymes, drugs, receptors, sorbents, immunosorbents and other biologically active molecules. (2) Artificial cells, microcapsules ...recombinant hemoglobin, and others. Chemistry, methods, in-vitro studies, in-vivo evaluations and clinical results. (4) Microencapsulation and other

Artificial Cells, Blood Substitutes, and Immobilization Biotechnology, Volume 22 Number 4, 1994.

DTIC Science & Technology

1994-01-01

culture, microorganisms, enzymes, drugs, receptors, sorbents, immunosorbents and other biologically active molecules. (2) Artificial cells, microcapsules ...recombinant hemoglobin, and others. Chemistry, methods, in-vitro studies, in-vivo evaluations and clinical results. (4) Microencapsulation and other

Hematologic reference values for clinically healthy captive golden conures (Guaruba guarouba).

PubMed

Prioste, Fabíola Eloisa Setim; Zwarg, Ticiana; Teixeira, Rodrigo Hidalgo; Vanstreels, Ralph Eric Thijl; Rocha, Arnaldo; Matushima, Eliana Reiko

2012-12-01

Golden conures or ararajubas (Guaruba guarouba) are endangered parrots endemic to the Brazilian Amazon forest. Body mass, blood cell counts, and total plasma protein were determined for 70 clinically healthy golden conures captive at zoologic parks and private breeder facilities in Brazil. Hematologic results (mean +/- SD) were: Erythrocytes 3.6 +/- 0.5 x 10(6) cells/mm3, hemoglobin 12.8 +/- 1.4 g/dl, packed cell volume 46 +/- 3.8%, mean corpuscular volume 132 +/- 20 fl, mean corpuscular hemoglobin (MCH) 36 +/- 5.7 pg, mean corpuscular hemoglobin concentration (MCHC) 28 +/- 3.5%, thrombocytes 26.3 +/- 9.3 x 10(3) cells/mm3, leukocytes 11.9 +/- 4.5 x 10(3) cells/mm3, heterophils 6284 +/- 2715 cells/mm3, lymphocytes 5473 +/- 2408 cells/ mm3, monocytes 113 +/- 162 cells/mm3, eosinophils 10 +/- 42 cells/mm3, basophils 27 +/- 64 cells/mm3. Body mass was 254 +/- 24.9 g and total plasma protein (TPP) was 3.54 +/- 0.58 g/dl. No statistical differences were observed between genders within age groups. Differences between juveniles (J) and adults (A) were identified for TPP (J < A), MCH (J > A), and MCHC (J > A). These results provide reliable reference values for the clinical interpretation of hematologic results for the species. Hematology may be an important tool for population health investigations on free-ranging golden conure populations and will also be essential to survey the health of release candidates in future reintroduction programs.

Pathophysiology of infectious hematopoietic necrosis virus disease in rainbow trout: hematological and blood chemical changes in moribund fish

USGS Publications Warehouse

Amend, D.F.; Smith, L.

1975-01-01

Infectious hematopoietic necrosis (IHN) is a rhabdoviral disease of rainbow trout (Salmo gairdneri). Trout were injected with IHNV, and various hematological and biochemical measurements of clinically ill fish were compared to uninfected controls. Infected fish had reduced corpuscular counts, hemoglobin, and packed cell volume, but normal mean corpuscular volume, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration. The percentage of immature erythrocytes was increased, but the percentage of leukocytes was unchanged. Differential leukocyte counts showed a significant decrease in neutrophils, increase in lymphocytes, but no change in monocytes. Unidentifiable necrobiotic cells were prevelant in blood smears and hematopoietic tissue imprints. Plasma bicarbonate, chloride, calcium, phosphorus, bilirubin, and osmolality were significantly reduced, but plasma glucose and anterior kidney ascorbate were unchanged. Plasma pH increased and the alpha fractions of the serum proteins were altered. No change was found in plasma enzymes, except that a LDH isozyme was significantly increased. The alkali reserve was diminished and alterations in acid-base and fluid balance occurred. Death probably resulted from a severe electrolyte and fluid imbalance caused by renal failure.

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

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.

Remedial Investigation/Baseline Risk Assessment for the Ravines and Beach Area Study areas of the Surplus Operable Unit, Fort Sheridan, Illinois, Volume 3 - BRA Text and BRA Appendices A-L

DTIC Science & Technology

1998-04-13

and Sydnor, 1968). The lymphoid system can also be affected resulting in lymphopenia. Toxic effects have been observed in the rapidly dividing cells ...polycyclic aromatic hydrocarbons have demonstrated the toxic effects of these compounds on rapidly proliferating cells . An intraperitoneal injection...b); however, higher doses are reported to result in testicular effects and decreased hemoglobin and packed cell volume (Kluwe et al, 1982; Gray et

Cell Salvage Used in Scoliosis Surgery: Is It Really Effective?

PubMed

Liu, Jia-Ming; Fu, Bi-Qi; Chen, Wen-Zhao; Chen, Jiang-Wei; Huang, Shan-Hu; Liu, Zhi-Li

2017-05-01

Scoliosis surgery usually is associated with large volume of intraoperative blood loss, and cell salvage is used commonly to filter and retranfusion autologous blood to patients. The efficacy of using cell salvage in scoliosis surgery, however, is still controversial. The purpose of this study is to make clear that intraoperative use of cell salvage is effective to decrease the volume of perioperative allogenic blood transfusion in scoliosis surgery. A meta-analysis was conducted to identify the relevant studies from PubMed, Embase, Medline, Cochrane library, and Google scholar until July 2016. All randomized trials and controlled clinical studies comparing the clinical outcomes of using cell salvage versus noncell salvage in scoliosis surgery were retrieved for the meta-analysis. The data were analyzed by RevMan 5.3. A total of 7 studies with 562 patients were included in this meta-analysis. Based on the analysis, the volumes of perioperative and postoperative allogenic red blood cell (RBC) transfusion in cell salvage group were significantly less than those in control group (P = 0.04 and P = 0.01); however, no significant difference was detected in the amount of intraoperative allogenic RBC transfusion and the risk of patients needing allogenic blood transfusion between the 2 groups (P = 0.14 and P = 0.61). Both the hemoglobin and hematocrit levels on the first day after surgery were significantly greater in cell salvage group than those in control group (P = 0.002 and P < 0.001). No significant differences, however, were noted in neither hemoglobin nor hematocrit level at the time of discharge between the 2 groups (P = 0.76 and P = 0.32). One of the included study reported the number of patients with complications related to transfusion in the two groups, which was not significant different (P = 0.507). Cell salvage significantly reduced the volumes of perioperative and postoperative allogenic RBC transfusion in scoliosis surgery and increased the hemoglobin and hematocrit levels on the first day postoperatively. In addition, it seemed not to increase the rate of transfusion complications during the surgery. Copyright © 2017 Elsevier Inc. All rights reserved.

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

Theory of nematic order with aggregate dehydration for reversibly assembling proteins in concentrated solutions: Application to sickle-cell hemoglobin polymers

NASA Astrophysics Data System (ADS)

Hentschke, Reinhard; Herzfeld, Judith

1991-06-01

The reversible association of globular protein molecules in concentrated solution leads to highly polydisperse fibers, e.g., actin filaments, microtubules, and sickle-cell hemoglobin fibers. At high concentrations, excluded-volume interactions between the fibers lead to spontaneous alignment analogous to that in simple lyotropic liquid crystals. However, the phase behavior of reversibly associating proteins is complicated by the threefold coupling between the growth, alignment, and hydration of the fibers. In protein systems aggregates contain substantial solvent, which may cause them to swell or shrink, depending on osmotic stress. Extending previous work, we present a model for the equilibrium phase behavior of the above-noted protein systems in terms of simple intra- and interaggregate interactions, combined with equilibration of fiber-incorporated solvent with the bulk solvent. Specifically, we compare our model results to recent osmotic pressure data for sickle-cell hemoglobin and find excellent agreement. This comparison shows that particle interactions sufficient to cause alignment are also sufficient to squeeze significant amounts of solvent out of protein fibers. In addition, the model is in accord with findings from independent sedimentation and birefringence studies on sickle-cell hemoglobin.

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.

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.

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.

Hematological changes in nephritis in poultry induced by diets high in protein, high in calcium, containing urea, or deficient in vitamin A.

PubMed

Chandra, M; Singh, B; Singh, N; Ahuja, S P

1984-04-01

Nephritis was induced in 300, 18-day-old male Arbor Acre broiler chicks by feeding diets high (42.28%) in protein, high (3.27%) in calcium, containing urea (5%), or deficient in vitamin A. Various hematological parameters were studied at weekly intervals. Normocytic-normochromic anemia, characterized by a decrease in total erythrocyte counts, hemoglobin, packed cell volume, and an increase in erythrocyte sedimentation rate, was evident in the birds kept on diets high in protein, high in calcium, or deficient in vitamin A. Increased total erythrocytes, hemoglobin packed cell volume, and erythrocyte sedimentation rate was observed in birds fed urea. Differential leucocyte counts revealed lymphopenia, heterophilia and monocytosis in birds kept on diets high in protein, containing urea, or deficient in vitamin A. However, lymphocytosis, heteropenia , and monocytosis were recorded in birds fed the high calcium diet.

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.

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.)

Kolaviron and vitamin E ameliorate hematotoxicity and oxidative stress in brains of prepubertal rats treated with an anticonvulsant phenytoin.

PubMed

Owoeye, Olatunde; Adedara, Isaac A; Bakare, Oluwafemi S; Adeyemo, Oluwatobi A; Egun, Christa; Farombi, Ebenezer O

2014-06-01

Phenytoin (PHT), an anticonvulsant agent, widely used for the treatment of epilepsy has been reported to exhibit toxic side effects. The present study investigated the protective effects of kolaviron and vitamin E on hematotoxicity and neurotoxicity induced by phenytoin, in prepubertal male rats. The animals were treated with PHT (75 mg/kg) separately or in combination with either kolaviron (200 mg/kg) or vitamin E (500 mg/kg) for 14 days. Phenytoin treatment significantly decreased the hemoglobin, white blood cells, lymphocytes and mean corpuscular volume levels without affecting red blood cell, packed cell volume, neutrophils, mean corpuscular hemoglobin and mean corpuscular hemoglobin concentration when compared with the control rats. There was a significant increase in lipid peroxidation and hydrogen peroxide levels with marked depletion in antioxidant status in brains of PHT-treated rats when compared with the control. Although PHT treatment had no effect on the granular layer, widest diameter of Purkinje cells and Purkinje layer of the cerebellum, it significantly reduced its molecular layer and the density of Purkinje cell. Administration of PHT significantly reduced the densities of the granule cells of the dentate gyrus and the pyramidal neurons of the cornu ammonis of hippocampus proper. Co-treatment with kolaviron and vitamin E effectively reversed the PHT-mediated alterations in the hematology, brain antioxidant status and histomorphometry when compared to PHT only. Taken together, the present data indicate the abilities of kolaviron and vitamin E to ameliorate phenytoin-induced hematotoxicity and oxidative stress in brains of rats.

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

Disorders of erythrocyte hydration.

PubMed

Gallagher, Patrick G

2017-12-21

The erythrocyte contains a network of pathways that regulate salt and water content in the face of extracellular and intracellular osmotic perturbations. This allows the erythrocyte to maintain a narrow range of cell hemoglobin concentration, a process critical for normal red blood cell function and survival. Primary disorders that perturb volume homeostasis jeopardize the erythrocyte and may lead to its premature destruction. These disorders are marked by clinical, laboratory, and physiologic heterogeneity. Recent studies have revealed that these disorders are also marked by genetic heterogeneity. They have implicated roles for several proteins, PIEZO1, a mammalian mechanosensory protein; GLUT1, the glucose transporter; SLC4A1, the anion transporter; RhAG, the Rh-associated glycoprotein; KCNN4, the Gardos channel; and ABCB6, an adenosine triphosphate-binding cassette family member, in the maintenance of erythrocyte volume homeostasis. Secondary disorders of erythrocyte hydration include sickle cell disease, thalassemia, hemoglobin CC, and hereditary spherocytosis, where cellular dehydration may be a significant contributor to disease pathology and clinical complications. Understanding the pathways regulating erythrocyte water and solute content may reveal innovative strategies to maintain normal volume in disorders associated with primary or secondary cellular dehydration. These mechanisms will serve as a paradigm for other cells and may reveal new therapeutic targets for disease prevention and treatment beyond the erythrocyte. © 2017 by The American Society of Hematology.

Hemoglobin and mean platelet volume predicts diffuse T1-MRI white matter volume decrease in sickle cell disease patients.

PubMed

Choi, Soyoung; Bush, Adam M; Borzage, Matthew T; Joshi, Anand A; Mack, William J; Coates, Thomas D; Leahy, Richard M; Wood, John C

2017-01-01

Sickle cell disease (SCD) is a life-threatening genetic condition. Patients suffer from chronic systemic and cerebral vascular disease that leads to early and cumulative neurological damage. Few studies have quantified the effects of this disease on brain morphometry and even fewer efforts have been devoted to older patients despite the progressive nature of the disease. This study quantifies global and regional brain volumes in adolescent and young adult patients with SCD and racially matched controls with the aim of distinguishing between age related changes associated with normal brain maturation and damage from sickle cell disease. T1 weighted images were acquired on 33 clinically asymptomatic SCD patients (age = 21.3 ± 7.8; F = 18, M = 15) and 32 racially matched control subjects (age = 24.4 ± 7.5; F = 22, M = 10). Exclusion criteria included pregnancy, previous overt stroke, acute chest, or pain crisis hospitalization within one month. All brain volume comparisons were corrected for age and sex. Globally, grey matter volume was not different but white matter volume was 8.1% lower (p = 0.0056) in the right hemisphere and 6.8% (p = 0.0068) in the left hemisphere in SCD patients compared with controls. Multivariate analysis retained hemoglobin (β = 0.33; p = 0.0036), sex (β = 0.35; p = 0.0017) and mean platelet volume (β = 0.27; p = 0.016) as significant factors in the final prediction model for white matter volume for a combined r 2 of 0.37 (p < 0.0001). Lower white matter volume was confined to phylogenetically younger brain regions in the anterior and middle cerebral artery distributions. Our findings suggest that there are diffuse white matter abnormalities in SCD patients, especially in the frontal, parietal and temporal lobes, that are associated with low hemoglobin levels and mean platelet volume. The pattern of brain loss suggests chronic microvascular insufficiency and tissue hypoxia as the causal mechanism. However, longitudinal studies of global and regional brain morphometry can help us give further insights on the pathophysiology of SCD in the brain.

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

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.

Orthotopic AY-27 rat bladder urothelial cell carcinoma model presented an elevated methemoglobin proportion in the increased total hemoglobin content when evaluated in vivo by single-fiber reflectance spectroscopy

NASA Astrophysics Data System (ADS)

Sun, Tengfei; Davis, Carole A.; Hurst, Robert E.; Slaton, Joel W.; Piao, Daqing

2017-02-01

In vivo single-fiber reflectance spectroscopy (SfRS) was performed on an orthotopic AY-27 rat bladder urothelial cell carcinoma model to explore potential spectroscopic features revealing neoplastic changes. AY-27 bladder tumor cells were intravesically instilled in four rats and allowed to implant and grow for one week, with two additional rats as the control. A total of 107 SfRS measurements were taken from 27 sites on two control bladders and 80 from four AY-27 treated bladders. The spectral profiles obtained from AY-27 treated bladders revealed various levels of a methemoglobin (MetHb) characteristic spectral feature around 635nm. A multisegment spectral analysis method estimated concentrations of five chromophore compositions including oxyhemoglobin, deoxyhemoglobin, MetHb, lipid and water. The total hemoglobin concentration ([HbT]), the MetHb proportion in the total hemoglobin and the lipid volume content showed possible correlations. The 80 measurements from the AY-27 treated bladders could separate to three sub-sets according to the MetHb proportion. Specifically, 72 were in subset 1 with low proportion (5.3%<[MetHb]<7%), 6 in subset 2 with moderate proportion (7%<[MetHb]<30%), and 2 in subset 3 with significant proportion (>30%). When grouped according to [MetHB], the [HbT] increased from 368 μM of subset 1 to 488 μM of subset 2 to 541 μM of subset 3, in comparison to the 285 μM of the control. The increased total hemoglobin and the elevation of MetHb proportion may signify angiogenesis and degradation in hemoglobin oxygen-transport. Additionally, the lipid volume content decreased from 2.58% in the control to <0.2% in the tumor groups, indicating disruption of subepithelium tissue architecture.

Haematolohical profile of subacute oral toxicity of molybdenum and ameliorative efficacy of copper salt in goats.

PubMed

Kusum; Raina, R; Verma, P K; Pankaj, N K; Kant, V; Kumar, J; Srivastava, A K

2010-07-01

Molybdenum toxicity produces a state of secondary hypocuprosis, resulting into alterations in normal hematological profile. In the present study, ammonium molybdate alone and with copper sulfate (II) pentahydrate (ameliorative agent) was administered orally for 30 consecutive days in healthy goats of group 1 and 2, respectively, to access the effect on the hematological profile on different predetermined days of dosing. Administration of ammonium molybdate alone produced significant decline in the mean values of hemoglobin (Hb), packed cell volume (PCV), total leukocyte count (TLC), total erythrocyte count (TEC), and mean corpuscular hemoglobin concentration (MCHC), with a significant increase in neutrophil level and mean corpuscular volume (MCV). However, values of erythrocyte sedimentation rate, mean corpuscular hemoglobin, and differential leukocyte count were not significantly altered. On comparing observations of ameliorative group with the group 1 goats, it is concluded that the ameliorative copper salt has beneficial effects in alleviating the alterations in the values of Hb, PCV, TLC, TEC, MCV, MCHC, and neutrophils.

Haematolohical Profile of Subacute Oral Toxicity of Molybdenum and Ameliorative Efficacy of Copper Salt in Goats

PubMed Central

Kusum; Raina, R.; Verma, P. K.; Pankaj, N. K.; Kant, V.; Kumar, J.; Srivastava, A. K.

2010-01-01

Molybdenum toxicity produces a state of secondary hypocuprosis, resulting into alterations in normal hematological profile. In the present study, ammonium molybdate alone and with copper sulfate (II) pentahydrate (ameliorative agent) was administered orally for 30 consecutive days in healthy goats of group 1 and 2, respectively, to access the effect on the hematological profile on different predetermined days of dosing. Administration of ammonium molybdate alone produced significant decline in the mean values of hemoglobin (Hb), packed cell volume (PCV), total leukocyte count (TLC), total erythrocyte count (TEC), and mean corpuscular hemoglobin concentration (MCHC), with a significant increase in neutrophil level and mean corpuscular volume (MCV). However, values of erythrocyte sedimentation rate, mean corpuscular hemoglobin, and differential leukocyte count were not significantly altered. On comparing observations of ameliorative group with the group 1 goats, it is concluded that the ameliorative copper salt has beneficial effects in alleviating the alterations in the values of Hb, PCV, TLC, TEC, MCV, MCHC, and neutrophils. PMID:21170251

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.

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.

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.

Effects of hydroxyurea on blood rheology in sickle cell anemia: A two-years follow-up study.

PubMed

Lemonne, Nathalie; Möckesch, Berenike; Charlot, Keyne; Garnier, Yohann; Waltz, Xavier; Lamarre, Yann; Antoine-Jonville, Sophie; Etienne-Julan, Maryse; Hardy-Dessources, Marie-Dominique; Romana, Marc; Connes, Philippe

2017-01-01

The aim of the present study was to test the effects of hydroxyurea (HU) therapy on clinical, hematological and hemorheological parameters in adult patients with sickle cell anemia (SCA). Hematological and hemorheological parameters were measured in 28 SCA patients before HU therapy (i.e., baseline) and at 6, 12 and 24 months of treatment. RBC deformability was determined by ektacytometry at 30 Pa. RBC aggregation properties were investigated by light-backscatter method. Blood viscosity was measured at 225 s-1 by a cone-plate viscometer. The rates of vaso-occlusive crises and acute chest syndrome were lower at 1 and 2 years of HU therapy compared to baseline. The proportion of patients with leg ulcers tended to decrease after 2 years of treatment. Hemoglobin oxygen saturation improved with HU therapy. HU therapy induced a decrease of platelet and white blood cell counts and a rise in fetal hemoglobin level and mean cell volume. While hemoglobin concentrations increased under HU, blood viscosity remained unchanged all along the study. RBC deformability increased over baseline values at 6 months of HU therapy and continued to rise until the end of the follow-up period. In conclusion, the improvement in RBC deformability probably compensates the increase of hemoglobin on blood viscosity and participates to the improvement of the clinical status of patients.

Magnetic measurements on human erythrocytes: Normal, beta thalassemia major, and sickle

NASA Astrophysics Data System (ADS)

Sakhnini, Lama

2003-05-01

In this article magnetic measurements were made on human erythrocytes at different hemoglobin states (normal and reduced hemoglobin). Different blood samples: normal, beta thalassemia major, and sickle were studied. Beta thalassemia major and sickle samples were taken from patients receiving lifelong blood transfusion treatment. All samples examined exhibited diamagnetic behavior. Beta thalassemia major and sickle samples showed higher diamagnetic susceptibilities than that for the normal, which was attributed to the increase of membrane to hemoglobin volume ratio of the abnormal cells. Magnetic measurements showed that the erythrocytes in the reduced state showed less diamagnetic response in comparison with erythrocytes in the normal state. Analysis of the paramagnetic component of magnetization curves gave an effective magnetic moment of μeff=7.6 μB per reduced hemoglobin molecule. The same procedure was applied to sickle and beta thalassemia major samples and values for μeff were found to be comparable to that of the normal erythrocytes.

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.

Parathyroid hormone ablation alters erythrocyte parameters that are rescued by calcium-sensing receptor gene deletion

PubMed Central

Romero, Jose R.; Youte, Rodeler; Brown, Edward M.; Pollak, Martin R.; Goltzman, David; Karaplis, Andrew; Pong, Lie-Chin; Chien, Lawrence; Chattopadhyay, Naibedya; Rivera, Alicia

2013-01-01

The mechanisms by which parathyroid hormone (PTH) produces anemia, are unclear. Parathyroid hormone secretion is regulated by the extracellular Ca2+-sensing receptor. We investigated the effects of ablating PTH on hematological indices and erythrocytes volume regulation in wild-type, PTH-null and Ca2+-sensing receptor-null/PTH-null mice. The erythrocyte parameters were measured in whole mouse blood and volume regulatory systems were determined by plasma membrane K+ fluxes and osmotic fragility was measured by hemoglobin determination at varying osmolarities. We observed that the absence of PTH significantly increases mean erythrocyte volume and reticulocyte counts, while decreasing erythrocyte counts, hemoglobin, hematocrit, and mean corpuscular hemoglobin concentration. These changes were accompanied by increases in erythrocyte cation content, a denser cell population and increased K+ permeability, which were in part mediated by activation of the K+/Cl− cotransporter and Gardos channel. In addition we observed that erythrocyte osmotic fragility in PTH-null compared with wild-type mice was enhanced. When Ca2+-sensing receptor gene was deleted on the background of PTH-null mice, we observed that several of the alterations in erythrocyte parameters of PTH-null mice were largely rescued, particularly those related to erythrocyte volume, K+ fluxes and osmotic fragility, and became similar to those observed in wild-type mice. Our results demonstrate that Ca2+-sensing receptor and parathyroid hormone are functionally coupled to maintain erythrocyte homeostasis. PMID:23528155

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.

Molecular analysis and association with clinical and laboratory manifestations in children with sickle cell anemia

PubMed Central

Camilo-Araújo, Roberta Faria; Amancio, Olga Maria Silverio; Figueiredo, Maria Stella; Cabanãs-Pedro, Ana Carolina; Braga, Josefina Aparecida Pellegrini

2014-01-01

Objectives To analyze the frequency of βS-globin haplotypes and alpha-thalassemia, and their influence on clinical manifestations and the hematological profile of children with sickle cell anemia. Method The frequency of βS-globin haplotypes and alpha-thalassemia and any association with clinical and laboratorial manifestations were determined in 117 sickle cell anemia children aged 3–71 months. The confirmation of hemoglobin SS and determination of the haplotypes were achieved by polymerase chain reaction-restriction fragment length polymorphism, and alpha-thalassemia genotyping was by multiplex polymerase chain reaction (single-tube multiplex-polymerase chain reaction). Results The genotype distribution of haplotypes was 43 (36.7%) Central African Republic/Benin, 41 (35.0%) Central African Republic/Central African Republic, 20 (17.0%) Rare/atypical, and 13 (11.1%) Benin/Benin. The frequency of the α3.7 deletion was 1.71% as homozygous (−α3.7/−α3.7) and 11.9% as heterozygous (−α3.7/αα). The only significant association in respect to haplotypes was related to the mean corpuscular volume. The presence of alpha-thalassemia was significantly associated to decreases in mean corpuscular volume, mean corpuscular hemoglobin and reticulocyte count and to an increase in the red blood cell count. There were no significant associations of βS-globin haplotypes and alpha-thalassemia with clinical manifestations. Conclusions In the study population, the frequency of alpha-thalassemia was similar to published data in Brazil with the Central African Republic haplotype being the most common, followed by the Benin haplotype. βS-globin haplotypes and interaction between alpha-thalassemia and sickle cell anemia did not influence fetal hemoglobin concentrations or the number of clinical manifestations. PMID:25305165

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.

Computational Model for Tumor Oxygenation Applied to Clinical Data on Breast Tumor Hemoglobin Concentrations Suggests Vascular Dilatation and Compression.

PubMed

Welter, Michael; Fredrich, Thierry; Rinneberg, Herbert; Rieger, Heiko

2016-01-01

We present a computational model for trans-vascular oxygen transport in synthetic tumor and host tissue blood vessel networks, aiming at qualitatively explaining published data of optical mammography, which were obtained from 87 breast cancer patients. The data generally show average hemoglobin concentration to be higher in tumors versus host tissue whereas average oxy-to total hemoglobin concentration (vascular segment RBC-volume-weighted blood oxygenation) can be above or below normal. Starting from a synthetic arterio-venous initial network the tumor vasculature was generated by processes involving cooption, angiogenesis, and vessel regression. Calculations of spatially resolved blood flow, hematocrit, oxy- and total hemoglobin concentrations, blood and tissue oxygenation were carried out for ninety tumor and associated normal vessel networks starting from various assumed geometries of feeding arteries and draining veins. Spatial heterogeneity in the extra-vascular partial oxygen pressure distribution can be related to various tumor compartments characterized by varying capillary densities and blood flow characteristics. The reported higher average hemoglobin concentration of tumors is explained by growth and dilatation of tumor blood vessels. Even assuming sixfold metabolic rate of oxygen consumption in tumorous versus host tissue, the predicted oxygen hemoglobin concentrations are above normal. Such tumors are likely associated with high tumor blood flow caused by high-caliber blood vessels crossing the tumor volume and hence oxygen supply exceeding oxygen demand. Tumor oxy- to total hemoglobin concentration below normal could only be achieved by reducing tumor vessel radii during growth by a randomly selected factor, simulating compression caused by intra-tumoral solid stress due to proliferation of cells and extracellular matrix. Since compression of blood vessels will impede chemotherapy we conclude that tumors with oxy- to total hemoglobin concentration below normal are less likely to respond to chemotherapy. Such behavior was recently reported for neo-adjuvant chemotherapy of locally advanced breast tumors.

Computational Model for Tumor Oxygenation Applied to Clinical Data on Breast Tumor Hemoglobin Concentrations Suggests Vascular Dilatation and Compression

PubMed Central

Welter, Michael; Fredrich, Thierry; Rinneberg, Herbert; Rieger, Heiko

2016-01-01

We present a computational model for trans-vascular oxygen transport in synthetic tumor and host tissue blood vessel networks, aiming at qualitatively explaining published data of optical mammography, which were obtained from 87 breast cancer patients. The data generally show average hemoglobin concentration to be higher in tumors versus host tissue whereas average oxy-to total hemoglobin concentration (vascular segment RBC-volume-weighted blood oxygenation) can be above or below normal. Starting from a synthetic arterio-venous initial network the tumor vasculature was generated by processes involving cooption, angiogenesis, and vessel regression. Calculations of spatially resolved blood flow, hematocrit, oxy- and total hemoglobin concentrations, blood and tissue oxygenation were carried out for ninety tumor and associated normal vessel networks starting from various assumed geometries of feeding arteries and draining veins. Spatial heterogeneity in the extra-vascular partial oxygen pressure distribution can be related to various tumor compartments characterized by varying capillary densities and blood flow characteristics. The reported higher average hemoglobin concentration of tumors is explained by growth and dilatation of tumor blood vessels. Even assuming sixfold metabolic rate of oxygen consumption in tumorous versus host tissue, the predicted oxygen hemoglobin concentrations are above normal. Such tumors are likely associated with high tumor blood flow caused by high-caliber blood vessels crossing the tumor volume and hence oxygen supply exceeding oxygen demand. Tumor oxy- to total hemoglobin concentration below normal could only be achieved by reducing tumor vessel radii during growth by a randomly selected factor, simulating compression caused by intra-tumoral solid stress due to proliferation of cells and extracellular matrix. Since compression of blood vessels will impede chemotherapy we conclude that tumors with oxy- to total hemoglobin concentration below normal are less likely to respond to chemotherapy. Such behavior was recently reported for neo-adjuvant chemotherapy of locally advanced breast tumors. PMID:27547939

Low Volume Resuscitation with Cell Impermeants

DTIC Science & Technology

2016-04-01

to rise) and a fall in peripheral vascular resistance . In this model, hemorrhage and blood loss was controlled so any changes in hemoglobin...appealing. The increase in capillary filling together with reduced resistance to flow in these peripheral beds leads to increased blood flow and oxygen...delivery. The low resistance , compared to saline controls, likely represents a physical decompression of the capillary beds by controlling cell and

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 ...

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.

Hemoglobin degradation in malaria-infected erythrocytes determined from live cell magnetophoresis

PubMed Central

Moore, Lee R.; Fujioka, Hisashi; Williams, P. Stephen; Chalmers, Jeffrey J.; Grimberg, Brian; Zimmerman, Peter; Zborowski, Maciej

2013-01-01

During intra-erythrocytic development, malaria trophozoites digest hemoglobin, which leads to parasite growth and asexual replication while accumulating toxic heme. To avoid death, the parasite synthesizes insoluble hemozoin crystals in the digestive vacuole through polymerization of β-hematin dimers. In the process, the heme is converted to a high-spin ferriheme whose magnetic properties were studied as early as 1936 by Pauling et al. Here, by magnetophoretic cell motion analysis, we provide evidence for a graduated increase of live cell magnetic susceptibility with developing blood-stage parasites, compatible with the increase in hemozoin content and the mechanism used by P. falciparum to avoid heme toxicity. The measured magnetophoretic mobility of the erythrocyte infected with a late-stage schizont form was m = 2.94 × 10−6 mm3 s/kg, corresponding to the net volume magnetic susceptibility (relative to water) of Δχ = 1.80 × 10−6, significantly higher than that of the oxygenated erythrocyte (−0.18×10−6) but lower than that of the fully deoxygenated erythrocyte (3.33×10−6). The corresponding fraction of hemoglobin converted to hemozoin, calculated based on the known magnetic susceptibilities of hemoglobin heme and hemozoin ferriheme, was 0.50, in agreement with the published biochemical and crystallography data. Magnetophoretic analysis of live erythrocytes could become significant for antimalarial drug susceptibility and resistance determination. PMID:16461330

Parathyroid hormone ablation alters erythrocyte parameters that are rescued by calcium-sensing receptor gene deletion.

PubMed

Romero, Jose R; Youte, Rodeler; Brown, Edward M; Pollak, Martin R; Goltzman, David; Karaplis, Andrew; Pong, Lie-Chin; Chien, Lawrence; Chattopadhyay, Naibedya; Rivera, Alicia

2013-07-01

The mechanisms by which parathyroid hormone (PTH) produces anemia are unclear. Parathyroid hormone secretion is regulated by the extracellular Ca2+ -sensing receptor. We investigated the effects of ablating PTH on hematological indices and erythrocytes volume regulation in wild-type, PTH-null, and Ca2+ -sensing receptor-null/PTH-null mice. The erythrocyte parameters were measured in whole mouse blood, and volume regulatory systems were determined by plasma membrane K+ fluxes, and osmotic fragility was measured by hemoglobin determination at varying osmolarities. We observed that the absence of PTH significantly increases mean erythrocyte volume and reticulocyte counts, while decreasing erythrocyte counts, hemoglobin, hematocrit, and mean corpuscular hemoglobin concentration. These changes were accompanied by increases in erythrocyte cation content, a denser cell population, and increased K+ permeability, which were in part mediated by activation of the K+ /Cl- cotransporter and Gardos channel. In addition we observed that erythrocyte osmotic fragility in PTH-null compared with wild-type mice was enhanced. When Ca2+ -sensing receptor gene was deleted on the background of PTH-null mice, we observed that several of the alterations in erythrocyte parameters of PTH-null mice were largely rescued, particularly those related to erythrocyte volume, K+ fluxes and osmotic fragility, and became similar to those observed in wild-type mice. Our results demonstrate that Ca2+ -sensing receptor and parathyroid hormone are functionally coupled to maintain erythrocyte homeostasis. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

Anemia, transfusion, and phlebotomy practices in critically ill patients with prolonged ICU length of stay: a cohort study

PubMed Central

Chant, Clarence; Wilson, Gail; Friedrich, Jan O

2006-01-01

Introduction Anemia among the critically ill has been described in patients with short to medium length of stay (LOS) in the intensive care unit (ICU), but it has not been described in long-stay ICU patients. This study was performed to characterize anemia, transfusion, and phlebotomy practices in patients with prolonged ICU LOS. Methods We conducted a retrospective chart review of consecutive patients admitted to a medical-surgical ICU in a tertiary care university hospital over three years; patients included had a continuous LOS in the ICU of 30 days or longer. Information on transfusion, phlebotomy, and outcomes were collected daily from days 22 to 112 of the ICU stay. Results A total of 155 patients were enrolled. The mean age, admission Acute Physiology and Chronic Health Evaluation II score, and median ICU LOS were 62.3 ± 16.3 years, 23 ± 8, and 49 days (interquartile range 36–70 days), respectively. Mean hemoglobin remained stable at 9.4 ± 1.4 g/dl from day 7 onward. Mean daily phlebotomy volume was 13.3 ± 7.3 ml, and 62% of patients received a mean of 3.4 ± 5.3 units of packed red blood cells at a mean hemoglobin trigger of 7.7 ± 0.9 g/dl after day 21. Transfused patients had significantly greater acuity of illness, phlebotomy volumes, ICU LOS and mortality, and had a lower hemoglobin than did those who were not transfused. Multivariate logistic regression analysis identified the following as independently associated with the likelihood of requiring transfusion in nonbleeding patients: baseline hemoglobin, daily phlebotomy volume, ICU LOS, and erythropoietin therapy (used almost exclusively in dialysis dependent renal failure in this cohort of patients). Small increases in average phlebotomy (3.5 ml/day, 95% confidence interval 2.4–6.8 ml/day) were associated with a doubling in the odds of being transfused after day 21. Conclusion Anemia, phlebotomy, and transfusions, despite low hemoglobin triggers, are common in ICU patients long after admission. Small decreases in phlebotomy volume are associated with significantly reduced transfusion requirements in patients with prolonged ICU LOS. PMID:17002795

Mean platelet volume (MPV) predicts middle distance running performance.

PubMed

Lippi, Giuseppe; Salvagno, Gian Luca; Danese, Elisa; Skafidas, Spyros; Tarperi, Cantor; Guidi, Gian Cesare; Schena, Federico

2014-01-01

Running economy and performance in middle distance running depend on several physiological factors, which include anthropometric variables, functional characteristics, training volume and intensity. Since little information is available about hematological predictors of middle distance running time, we investigated whether some hematological parameters may be associated with middle distance running performance in a large sample of recreational runners. The study population consisted in 43 amateur runners (15 females, 28 males; median age 47 years), who successfully concluded a 21.1 km half-marathon at 75-85% of their maximal aerobic power (VO2max). Whole blood was collected 10 min before the run started and immediately thereafter, and hematological testing was completed within 2 hours after sample collection. The values of lymphocytes and eosinophils exhibited a significant decrease compared to pre-run values, whereas those of mean corpuscular volume (MCV), platelets, mean platelet volume (MPV), white blood cells (WBCs), neutrophils and monocytes were significantly increased after the run. In univariate analysis, significant associations with running time were found for pre-run values of hematocrit, hemoglobin, mean corpuscular hemoglobin (MCH), red blood cell distribution width (RDW), MPV, reticulocyte hemoglobin concentration (RetCHR), and post-run values of MCH, RDW, MPV, monocytes and RetCHR. In multivariate analysis, in which running time was entered as dependent variable whereas age, sex, blood lactate, body mass index, VO2max, mean training regimen and the hematological parameters significantly associated with running performance in univariate analysis were entered as independent variables, only MPV values before and after the trial remained significantly associated with running time. After adjustment for platelet count, the MPV value before the run (p = 0.042), but not thereafter (p = 0.247), remained significantly associated with running performance. The significant association between baseline MPV and running time suggest that hyperactive platelets may exert some pleiotropic effects on endurance performance.

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.

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

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

PubMed

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

2017-05-02

Our aim was to evaluate the cut-off value and efficiency of using reticulocyte hemoglobin content as a marker to diagnose iron deficiency anemia in Chinese adults. 140 adults who needed bone marrow aspiration for diagnosis at the hematology department of the Peking Union Medical College Hospital were enrolled according to the inclusive and exclusive criteria. Venous blood samples were collected to detect complete blood count, including hemoglobin, reticulocyte hemoglobin content, hematocrit, mean cellular volume, corpuscular hemoglobin concentration, hemoglobin content, free erythrocyte protoporphyrin; iron indexes of serum ferritin, serum transferrin receptor, and unsaturated iron-binding capacity; and inflammation markers of C-reactive protein and α-acid glycoprotein. Bone marrow samples were obtained for the bone marrow iron staining, which was used as the standard for the evaluation of iron status in this study. Subjects were divided into three groups according to hemoglobin levels and bone marrow iron staining results: the IDA (iron deficiency anemia) group, the NIDA (non-iron deficiency anemia) group, and the control group. The differences of the above-mentioned indexes were compared among the three groups and the effect of inflammation was also considered. The cut-off value of reticulocyte hemoglobin content was determined by receiver operation curves. The IDA group ( n = 56) had significantly lower reticulocyte hemoglobin content, mean cellular volume, corpuscular hemoglobin concentration, hemoglobin content, and serum ferritin; and higher free erythrocyte protoporphyrin, unsaturated iron-binding capacity, and serum transferrin receptor ( p < 0.05) compared with the NIDA group ( n = 38) and control group ( n = 46). Hematocrit, serum ferritin, and unsaturated iron-binding capacity were significantly affected by inflammation while reticulocyte hemoglobin content and other parameters were not. The cut-off value of reticulocyte hemoglobin content for diagnosing iron deficiency anemia was 27.2 pg, with a sensitivity of 87.5% and a specificity of 92.9%. The cut-off values for mean cellular volume, serum ferritin, and serum transferrin receptor were 76.6, 12.9, and 4.89 mg/L, respectively. Reticulocyte hemoglobin content had the largest area under the curve of 0.929, while those for mean cellular volume, serum ferritin, serum transferrin receptor were 0.922, 0.887, and 0.900, respectively. Reticulocyte hemoglobin content has a high sensitivity and specificity in the diagnosis of iron deficiency anemia, and its comprehensive diagnostic efficacy is better than other traditional indicators-such as serum ferritin and serum transferrin receptor.

Association Between Hematological Indices and Coronary Calcification in Symptomatic Patients without History of Coronary Artery Disease

PubMed Central

Chaikriangkrai, Kongkiat; Kassi, Mahwash; Alchalabi, Sama; Bala, Sayf Khaleel; Adigun, Rosalyn; Botero, Sharleen; Chang, Su Min

2014-01-01

Background: Atherosclerotic coronary artery disease (CAD) has long been shown to involve chronic low-grade subclinical inflammation. However, whether there is association between hematological indices assessed by complete blood count (CBC) and coronary atherosclerotic burden has not been well studied. Materials and Methods: Consecutive 868 patients without known CAD who presented with acute chest pain to emergency department and underwent coronary artery calcium (CAC) scoring evaluation by multi-detector cardiac computed tomography were included in our study. Clinical characteristics and CBC indices were compared among different CAC groups. Results: The cohort comprised 60% male with a mean age of 61 (SD = 14) years. Median Framingham risk of CAD was 4% (range 1-16%). Median CAC score was 0 (IQR 0-43). Higher CAC groups had significantly higher Framingham risk of CAD than lower CAC groups (P < 0.001). Among different CAC categories, there was no statistically significant difference in hemoglobin level (p 0.45), mean corpuscular volume (p 0.43), mean corpuscular hemoglobin (p 0.28), mean corpuscular hemoglobin volume (p 0.36), red cell distribution width (0.42), total white blood cell counts (p 0.291), neutrophil counts (p 0.352), lymphocyte counts (p 0.92), neutrophil to lymphocyte ratio (p 0.68), monocyte count (p 0.48), and platelet counts (p 0.25). Conclusion: Our study did not detect significant association between hematological indices assessed with CBC and coronary calcification in symptomatic patients without known CAD. PMID:25317386

N-terminal pro-brain natriuretic peptide in prevalent peritoneal dialysis patients.

PubMed

Adachi, Yoko; Nishio, Akira

2008-01-01

Previous reports have shown that N-terminal pro-brain natriuretic peptide (NT-Pro-BNP) is a predictive marker for mortality in both peritoneal dialysis (PD) and hemodialysis (HD) patients. The aim of the present study was to clarify whether NT-Pro-BNP reflects a specific status in PD patients. We analyzed 40 stable PD patients, allocating them to one of two groups (20 each) according to the median value of NT-Pro-BNP: group A below and group B above 5423 pg/mL. In group B as compared with group A, red blood cell (RBC) counts, hemoglobin, hematocrit, sodium, chlorine, albumin, and daily urinary volume were significantly lower, and cardiothoracic ratio (CTR) and daily ultrafiltration volume were significantly higher. Patients using icodextrin and diabetic patients showed significantly higher NT-Pro-BNP values. We observed significant correlations between NT-Pro-BNP and RBC count, hematocrit, hemoglobin, sodium, chlorine, albumin, lactate dehydrogenase, CTR, daily urinary volume, and ultrafiltration volume. Multiple regression analysis revealed that increasing CTR and hyponatremia were significant predictors of an increase in NT-Pro-BNP. Our results indicate that increased serum NT-Pro-BNP well reflects anemia status, water balance, hyponatremia, and hypoalbuminemia in prevalent PD patients.

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.

Jerusalem artichoke enriched diet on growth performance, immuno-hematological changes and disease resistance against Aeromonas hydrophila in Asian seabass (Lates calcarifer).

PubMed

Syed Raffic Ali, Sajjad; Ambasankar, Kondusamy; Saiyad Musthafa, Mohamed; Harikrishnan, Ramasamy

2017-11-01

A 45 days feeding trial was conducted to study the effect of Jerusalem artichoke (JA) on growth performance, body composition, biochemical, immuno-hematological parameters and disease resistance in Asian seabass (Lates calcarifer) fingerlings against Aeromonas hydrophila. JA was supplemented at three different levels viz., control 0, 5, 10, and 20 g kg -1 in the commercial diet (403 g kg -1 protein and 89 g kg -1 lipid) in L. calcarifer. The results showed that there were no significant (P > 0.05) differences in various growth parameters, while the whole body composition showed significant differences (P < 0.05) between control and treatment groups. Hematological parameters showed that red blood cells (RBC), white blood cells (WBC), hemoglobin (Hb), pack cell volume (PCV), mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC) were not significantly (P > 0.05) affected by dietary supplementation of JA at different concentration. However, the mean corpuscular volume (MCV) was significantly (P < 0.05) higher in the fish fed with 20 g kg -1  JA supplemented diet. Biochemical parameters revealed that glucose, urea, cholesterol, and triglyceride showed significant (P < 0.05) differences between control and treatments groups. Interestingly, 20 g kg -1  JA supplemented diet significantly modulates the innate immune response and disease resistance against Aeromonas hydrophila compared with control and other treatment groups. The results of the study revealed that 20 g kg -1  JA supplementation has a beneficial effect in the biochemical, immunological and disease resistance in L. calcarifer juveniles. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

[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.

Serum free hemoglobin test

MedlinePlus

... the red blood cells. Most of the hemoglobin is found inside the red blood cells, not in the serum. Hemoglobin carries oxygen ... Hemoglobin (Hb) is the main component of red blood cells. It is a ... oxygen. This test is done to diagnose or monitor how severe ...

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

PubMed

Longeville, Stéphane; Stingaciu, Laura-Roxana

2017-09-05

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

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

DOE PAGES

Longeville, Stéphane; Stingaciu, Laura-Roxana

2017-09-05

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

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

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

Longeville, Stéphane; Stingaciu, Laura-Roxana

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

[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.

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 ...

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.

Effects of hydroxyurea treatment for patients with hemoglobin SC disease.

PubMed

Luchtman-Jones, Lori; Pressel, Sara; Hilliard, Lee; Brown, R Clark; Smith, Mary G; Thompson, Alexis A; Lee, Margaret T; Rothman, Jennifer; Rogers, Zora R; Owen, William; Imran, Hamayun; Thornburg, Courtney; Kwiatkowski, Janet L; Aygun, Banu; Nelson, Stephen; Roberts, Carla; Gauger, Cynthia; Piccone, Connie; Kalfa, Theodosia; Alvarez, Ofelia; Hassell, Kathryn; Davis, Barry R; Ware, Russell E

2016-02-01

Although hemoglobin SC (HbSC) disease is usually considered less severe than sickle cell anemia (SCA), which includes HbSS and HbS/β(0) -thalassemia genotypes, many patients with HbSC experience severe disease complications, including vaso-occlusive pain, acute chest syndrome, avascular necrosis, retinopathy, and poor quality of life. Fully 20 years after the clinical and laboratory efficacy of hydroxyurea was proven in adult SCA patients, the safety and utility of hydroxyurea treatment for HbSC patients remain unclear. Recent NHLBI evidence-based guidelines highlight this as a critical knowledge gap, noting HbSC accounts for ∼30% of sickle cell patients within the United States. To date, only 5 publications have reported short-term, incomplete, or conflicting laboratory and clinical outcomes of hydroxyurea treatment in a total of 71 adults and children with HbSC. We now report on a cohort of 133 adult and pediatric HbSC patients who received hydroxyurea, typically for recurrent vaso-occlusive pain. Hydroxyurea treatment was associated with a stable hemoglobin concentration; increased fetal hemoglobin (HbF) and mean corpuscular volume (MCV); and reduced white blood cell count (WBC), absolute neutrophil count (ANC), and absolute reticulocyte count (ARC). Reversible cytopenias occurred in 22% of patients, primarily neutropenia and thrombocytopenia. Painful events were reduced with hydroxyurea, more in patients >15 years old. These multicenter data support the safety and potentially salutary effects of hydroxyurea treatment for HbSC disease; however, a multicenter, placebo-controlled, Phase 3 clinical trial is needed to determine if hydroxyurea therapy has efficacy for patients with HbSC disease. © 2015 Wiley Periodicals, Inc.

Effects of PEG-PLA-nano Artificial Cells Containing Hemoglobin on Kidney Function and Renal Histology in Rats

PubMed Central

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

2012-01-01

This study is to investigate the long-term effects of PEG-PLA nano artificial cells containing hemoglobin (NanoRBC) on renal function and renal histology after 1/3 blood volume top loading in rats. The experimental rats received one of the following infusions: NanoRBC in Ringer lactate, Ringer lactate, stroma-free hemoglobin (SFHB), polyhemoglobin (PolyHb), autologous rat whole blood (rat RBC). Blood samples were taken before infusions and on days 1, 7 and 21 after infusions for biochemistry analysis. Rats were sacrificed on day 21 after infusions and kidneys were excised for histology examination. Infusion of SFHB induced significant decrease in renal function damage evidenced by elevated serum urea, creatinine and uric acid throughout the 21 days. Kidney histology in SFHb infusion group revealed focal tubular necrosis and intraluminal cellular debris in the proximal tubules, whereas the glomeruli were not observed damaged. In all the other groups, NanoRBC, PolyHb, Ringer lactate and rat RBC, there were no abnormalities in renal biochemistry or histology. In conclusion, injection of NanoRBC did not have adverse effects on renal function nor renal histology. PMID:18979292

Hemoglobin Aggregation in Single Red Blood Cells of Sickle Cell Anemia

NASA Astrophysics Data System (ADS)

Nishio, Izumi; Tanaka, Toyoichi; Sun, Shao-Tang; Imanishi, Yuri; Tsuyoshi Ohnishi, S.

1983-06-01

A laser light scattering technique was used to observe the extent of hemoglobin aggregation in solitary red blood cells of sickle cell anemia. Hemoglobin aggregation was confirmed in deoxygenated cells. The light scattering technique can also be applied to cytoplasmic studies of any biological cell.

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

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.

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

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.

Effects of isotretinoin on the platelet counts and the mean platelet volume in patients with acne vulgaris.

PubMed

Ataseven, Arzu; Ugur Bilgin, Aynur

2014-01-01

Aim. The aim of this study was to evaluate the platelet counts and the mean platelet volume in patients who received isotretinoin for the treatment of acne vulgaris. Method. A total of 110 patients were included in this retrospective study. Complete blood count parameters were recorded prior to and three-months following the treatment. Results. Both platelet counts and the mean platelet volume were significantly decreased following the treatment. No significant differences were noted on the levels of hemoglobin, hematocrit, and white blood cell count. Conclusion. Platelet counts and mean platelet volume significantly decreased following isotretinoin treatment. Since the decrease of platelet counts and the mean platelet volume was seen concomitantly, it is concluded that the effect of isotretinoin was through the suppression of bone marrow.

Dependence of erythroid differentiation on cell replication in dimethyl sulfoxide-treated friend leukemia-virus-infected cells

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

Wiens, A.W.; McClintock, P.R.; Papaconstantinou, J.

1976-01-01

The dimethyl sulfoxide (Me/sub 2/SO)-mediated induction of hemoglobin synthesis in Friend leukemia cells (a murine erythroblastoid cell line) is coupled with the number of cell replications occurring in the presence of inducer. Varying concentrations of proflavine increase the generation time of these cells from 24 hours to over 50 hours, and in each case the induction of hemoglobin synthesis follows the completion of two cell doublings. Once the induction is initiated, the rate of hemoglobin accumulation is not affected by proflavine. These data indicate that proflavine does not affect the transcription or translation of globin mRNA and that the delaymore » in induction of hemoglobin synthesis is due to its effect on the rate of cellular replication. In experiments using high concentrations of thymidine to block replication, hemoglobin accumulation is prevented only if the cells are blocked prior to 36 hours after Me/sub 2/SO addition. If the cells have completed two generations in the presence of Me/sub 2/SO, there is no effect upon their ability to synthesize hemoglobin even though their growth is arrested. Thus, the inhibition of hemoglobin synthesis by proflavine is not merely the result of a toxic effect on newly subcultured cells but is due to its effect on cellular replication. These experiments confirm that, after addition of Me/sub 2/SO, Friend leukemia cells require more than one complete cell cycle in order to synthesize hemoglobin.« less

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.

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

DOEpatents

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

1988-01-01

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

Perioperative Management of Sickle Cell Disease

PubMed Central

Adjepong, Kwame Ofori; Otegbeye, Folashade

2018-01-01

Over 30 million people worldwide have sickle cell disease (SCD). Emergent and non-emergent surgical procedures in SCD have been associated with relatively increased risks of peri-operative mortality, vaso-occlusive (painful) crisis, acute chest syndrome, post-operative infections, congestive heart failure, cerebrovascular accident and acute kidney injury. Pre-operative assessment must include a careful review of the patient’s known crisis triggers, baseline hematologic profile, usual transfusion requirements, pre-existing organ dysfunction and opioid use. Use of preoperative blood transfusions should be selective and decisions individualized based on the baseline hemoglobin, surgical procedure and anticipated volume of blood loss. Intra- and post-operative management should focus on minimizing hypoxia, hypothermia, acidosis, and intravascular volume depletion. Pre- and post-operative incentive spirometry use should be encouraged. PMID:29755709

Perioperative Management of Sickle Cell Disease.

PubMed

Adjepong, Kwame Ofori; Otegbeye, Folashade; Adjepong, Yaw Amoateng

2018-01-01

Over 30 million people worldwide have sickle cell disease (SCD). Emergent and non-emergent surgical procedures in SCD have been associated with relatively increased risks of peri-operative mortality, vaso-occlusive (painful) crisis, acute chest syndrome, post-operative infections, congestive heart failure, cerebrovascular accident and acute kidney injury. Pre-operative assessment must include a careful review of the patient's known crisis triggers, baseline hematologic profile, usual transfusion requirements, pre-existing organ dysfunction and opioid use. Use of preoperative blood transfusions should be selective and decisions individualized based on the baseline hemoglobin, surgical procedure and anticipated volume of blood loss. Intra- and post-operative management should focus on minimizing hypoxia, hypothermia, acidosis, and intravascular volume depletion. Pre- and post-operative incentive spirometry use should be encouraged.

CDC Grand Rounds: Improving the Lives of Persons with Sickle Cell Disease.

PubMed

Hulihan, Mary; Hassell, Kathryn L; Raphael, Jean L; Smith-Whitley, Kim; Thorpe, Phoebe

2017-11-24

Approximately 100,000 Americans have sickle cell disease (SCD), a group of recessively inherited red blood cell disorders characterized by abnormal hemoglobin, called hemoglobin S or sickle hemoglobin, in the red blood cells. Persons with hemoglobin SS or hemoglobin Sß 0 thalassemia, also known as sickle cell anemia (SCA), have the most severe form of SCD. Hemoglobin SC disease and hemoglobin Sß + thalassemia are other common forms of SCD. Red blood cells that contain sickle hemoglobin are inflexible and can stick to vessel walls, causing a blockage that slows or stops blood flow. When this happens, oxygen cannot reach nearby tissues, leading to attacks of sudden, severe pain, called pain crises, which are the clinical hallmark of SCD. The red cell sickling and poor oxygen delivery can also cause damage to the brain, spleen, eyes, lungs, liver, and multiple other organs and organ systems. These chronic complications can lead to increased morbidity, early mortality, or both. Tremendous strides in treating and preventing the complications of SCD have extended life expectancy. Now, nearly 95% of persons born with SCD in the United States reach age 18 years (1); however, adults with the most severe forms of SCD have a life span that is 20-30 years shorter than that of persons without SCD (2).

Serum-free Erythroid Differentiation for Efficient Genetic Modification and High-Level Adult Hemoglobin Production.

PubMed

Uchida, Naoya; Demirci, Selami; Haro-Mora, Juan J; Fujita, Atsushi; Raines, Lydia N; Hsieh, Matthew M; Tisdale, John F

2018-06-15

In vitro erythroid differentiation from primary human cells is valuable to develop genetic strategies for hemoglobin disorders. However, current erythroid differentiation methods are encumbered by modest transduction rates and high baseline fetal hemoglobin production. In this study, we sought to improve both genetic modification and hemoglobin production among human erythroid cells in vitro . To model therapeutic strategies, we transduced human CD34 + cells and peripheral blood mononuclear cells (PBMCs) with lentiviral vectors and compared erythropoietin-based erythroid differentiation using fetal-bovine-serum-containing media and serum-free media. We observed more efficient transduction (85%-93%) in serum-free media than serum-containing media (20%-69%), whereas the addition of knockout serum replacement (KSR) was required for serum-free media to promote efficient erythroid differentiation (96%). High-level adult hemoglobin production detectable by electrophoresis was achieved using serum-free media similar to serum-containing media. Importantly, low fetal hemoglobin production was observed in the optimized serum-free media. Using KSR-containing, serum-free erythroid differentiation media, therapeutic adult hemoglobin production was detected at protein levels with β-globin lentiviral transduction in both CD34 + cells and PBMCs from sickle cell disease subjects. Our in vitro erythroid differentiation system provides a practical evaluation platform for adult hemoglobin production among human erythroid cells following genetic manipulation.

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...

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.

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.

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

PubMed

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

2003-08-01

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

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

PubMed Central

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

2014-01-01

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

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.

The Role of Chlorogenic Acid Supplementation in Anemia and Mineral Disturbances Induced by 4-Tert-Octylphenol Toxicity.

PubMed

Koriem, Khaled M M; Arbid, Mahmoud S S; Gomaa, Nawal E

2018-01-02

4-tert-octylphenol (OP) is an endocrine-disrupting chemical that causes harmful effects to human health. Chlorogenic acid is the major dietary polyphenol present in various foods and beverages. The aim of the present study was to evaluate the protective role of chlorogenic acid in anemia and mineral disturbance occurring in OP toxicity in rats. Thirty-two male albino rats were divided into four equal groups (8 rats/group) as follows. The first (control) group was treated daily with an oral dose of 1 ml saline for two weeks. The second group was treated daily with an oral dose of 60 mg chlorogenic acid/kg body weight for two weeks. The third and fourth groups received daily intraperitoneal (ip) injections with 100 mg OP/kg body weight for two weeks; the fourth group was treated daily with an oral dose of 60 mg chlorogenic acid/kg body weight for three weeks starting one week before OP injections. The results revealed that OP induced significant decreases in hemoglobin, hematocrit, red blood cells, mean cell volume, mean cell hemoglobin, mean cell hemoglobin concentration, platelet count, white blood cells, lymphocyte and neutrophil percent, transferrin receptor, serum calcium, phosphorous, sodium, potassium, chloride, glutathione-S-transferase, glutathione peroxidase, catalase, glutathione reductase, and superoxide dismutase. Moreover, significant increases in serum hepcidin, ferritin, transferrin, erythropoietin, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, urea, creatinine, selenium, zinc, manganese, copper, iron, malondialdehyde, and protein carbonyl levels were found in OP groups. OP exposure also induced cell apoptosis. Chlorogenic acid pretreatment in OP-treated groups restored all the mentioned parameters to approach the normal values. In conclusion, chlorogenic acid protects from anemia and mineral disturbances in 4-tert-octylphenol toxicity by ameliorating oxidative stress and apoptosis.

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 .).

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.

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

A proposal to standardize reporting units for fecal immunochemical tests for hemoglobin.

PubMed

Fraser, Callum G; Allison, James E; Halloran, Stephen P; Young, Graeme P

2012-06-06

Fecal immunochemical tests for hemoglobin are replacing traditional guaiac fecal occult blood tests in population screening programs for many reasons. However, the many available fecal immunochemical test devices use a range of sampling methods, differ with regard to hemoglobin stability, and report hemoglobin concentrations in different ways. The methods for sampling, the mass of feces collected, and the volume and characteristics of the buffer used in the sampling device also vary among fecal immunochemical tests, making comparisons of test performance characteristics difficult. Fecal immunochemical test results may be expressed as the hemoglobin concentration in the sampling device buffer and, sometimes, albeit rarely, as the hemoglobin concentration per mass of feces. The current lack of consistency in units for reporting hemoglobin concentration is particularly problematic because apparently similar hemoglobin concentrations obtained with different devices can lead to very different clinical interpretations. Consistent adoption of an internationally accepted method for reporting results would facilitate comparisons of outcomes from these tests. We propose a simple strategy for reporting fecal hemoglobin concentration that will facilitate the comparison of results between fecal immunochemical test devices and across clinical studies. Such reporting is readily achieved by defining the mass of feces sampled and the volume of sample buffer (with confidence intervals) and expressing results as micrograms of hemoglobin per gram of feces. We propose that manufacturers of fecal immunochemical tests provide this information and that the authors of research articles, guidelines, and policy articles, as well as pathology services and regulatory bodies, adopt this metric when reporting fecal immunochemical test results.

Comparison of stored red blood cell washing techniques for priming extracorporeal circuits.

PubMed

Sasaki, Jun; Tirotta, Christopher; Lim, Hyunsoo; Kubes, Kathleen; Salvaggio, Jane; Hannan, Robert; Burke, Redmond; Ojito, Jorge

2018-03-01

The aim of this study was to compare three different blood washing techniques and describe the differences for the composition of the washed red blood cells (RBC). Stored RBCs less than 5 days old were washed using three different techniques. 1) Washing with normal saline with the COBE Model 2991 blood processor in the blood bank (BB-S). 2) Washing with normal saline with the Continuous AutoTransfusion System (C.A.T.S) in the operating room (OR-S). 3) Washing with Plasma-Lyte with the C.A.T.S in the operating room (OR-PL). Then, we compared the values for hemoglobin (Hb), hematocrit (Hct), blood volume, RBC volume, lactate, glucose, sodium and potassium of the three different groups. Forty-five units of RBCs were washed and analyzed (15 for each technique). The OR-S RBCs, when compared to the BB-S RBCs, had lower hemoglobin (g/dL) (22.8 vs 24.1, p=0.006), lower hematocrit (%) (67 vs 71, p=0.006), higher RBC volume (ml) (161 vs 130, p<0.001), higher glucose (mg/dL) (185 vs 46, p<0.001) and lower sodium (mmol/L) (153 vs 158, p<0.001). When compared to the OR-S RBCs, the OR-PL RBCs showed higher potassium (mmol/L) (5.3 vs 2, p<0.001) and lower sodium (mmol/L) (129 vs 153, p<0.001). RBCs washed with an autotransfusion device had a higher RBC volume and more physiological levels of glucose and sodium when compared with the blood processor in the blood bank. It can be an alternative option to use RBCs washed with an autotransfusion device for priming the extracorporeal circuits utilized in patients undergoing cardiac surgery.

Hemoglobin switching in sheep and goats. VI. Commitment of erythroid colony-forming cells to the synthesis of betaC globin

PubMed Central

1976-01-01

Bone marrow from mature goats and sheep was cultured in plasma clots, and three erythropoietin (ESF)-dependent responses-growth (colony formation), differentiation (globin production), and initiation of hemoglobin C (alpha2beta2C) synthesis--were quantitated. ESF concentrations below 0.01 U/ml supported colony growth and adult hemoglobin production in cultures of goat marrow, while maximal hemoglobin C synthesis (70%), as measured between 72 and 96 h in culture, required a 100-fold higher ESF concentration. Sheep marrow was cultured in a medium enriched to enhance growth and to permit complete maturation of colonies. These colonies active in hemoglobin synthesis between 24 and 96 h produced mainly adult hemoglobin, and only between 96 and 120 h did sheep colonies develop which produced mainly hemoglobin C (up to 70%). A similar heterogeneity may exist among goat colonies. Thus, when goat bone marrow was fractionated by unit gravity sedimentation, more hemoglobin C synthesis was observed in colonies derived from cells of intermediate sedimentation velocity than in colonies derived from the most rapidly sedimenting cells. Brief exposure of sheep (in vivo) and goat (in vitro) bone marrow to a high ESF concentration committed precursor cells to the generation of colonies which, even at low ESF concentration, produced hemoglobin C. Committment to hemoglobin phenotype appears to be an early and probably irreversible event in the development of an erythroid cell. PMID:993267

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.

Genetics Home Reference: autosomal recessive congenital methemoglobinemia

MedlinePlus

... it alters a molecule within these cells called hemoglobin . Hemoglobin carries oxygen to cells and tissues throughout the ... autosomal recessive congenital methemoglobinemia , some of the normal hemoglobin is replaced by an abnormal form called methemoglobin, ...

Nonpharmacological, blood conservation techniques for preventing neonatal anemia--effective and promising strategies for reducing transfusion.

PubMed

Carroll, Patrick D; Widness, John A

2012-08-01

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. Copyright © 2012 Elsevier Inc. All rights reserved.

The effect of climbing Mount Everest on spleen contraction and increase in hemoglobin concentration during breath holding and exercise.

PubMed

Engan, Harald K; Lodin-Sundström, Angelica; Schagatay, Fanny; Schagatay, Erika

2014-04-01

Release of stored red blood cells resulting from spleen contraction improves human performance in various hypoxic situations. This study determined spleen volume resulting from two contraction-evoking stimuli: breath holding and exercise before and after altitude acclimatization during a Mount Everest ascent (8848 m). Eight climbers performed the following protocol before and after the climb: 5 min ambient air respiration at 1370 m during rest, 20 min oxygen respiration, 20 min ambient air respiration at 1370 m, three maximal-effort breath holds spaced by 2 min, 10 min ambient air respiration, 5 min of cycling at 100 W, and finally 10 min ambient air respiration. We measured spleen volume by ultrasound and capillary hemoglobin (HB) concentration after each exposure, and heart rate (HR) and arterial oxygen saturation (Sao2) continuously. Mean (SD) baseline spleen volume was unchanged at 213 (101) mL before and 206 (52) mL after the climb. Before the climb, spleen volume was reduced to 184 (83) mL after three breath holds, and after the climb three breath holds resulted in a spleen volume of 132 (26) mL (p=0.032). After exercise, the preclimb spleen volume was 186 (89) mL vs. 112 (389) mL) after the climb (p=0.003). Breath hold duration and cardiovascular responses were unchanged after the climb. We concluded that spleen contraction may be enhanced by altitude acclimatization, probably reflecting both the acclimatization to chronic hypoxic exposure and acute hypoxia during physical work.

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 ...

The association between hematological parameters and metabolic syndrome in Iranian men: A single center large-scale study.

PubMed

Ahmadzadeh, Jamal; Mansorian, Behnam; Attari, Mohammad Mirza-Aghazadeh; Mohebbi, Ira; Naz-Avar, Raha; Moghadam, Karaim; Ghareh-Bagh, Seyyed Adel Khoshbou

Some studies have demonstrated that metabolic syndrome is associated with hematological parameters. The present study explores the relationship between hematological parameters and numbers of metabolic syndrome conditions in Iranian men. This cross-sectional study included 11,114 participants who were professional drivers of commercial motor vehicles, and were enrolled in the Iranian Health Surveys between 2014 and 2016. Diagnosis of metabolic syndrome was made according to International Diabetes Federation criteria. Clinical data, including anthropometric measurements and serum parameters, were collected. Odds ratios for hematological parameters and metabolic syndrome were calculated using binary logistic regression models. We found that hemoglobin; platelet, and white blood cell counts increased with increasing numbers of metabolic syndrome components (p<0.05 for all). The odds ratio of metabolic syndrome significantly increased across successive quartiles of platelet (1.00, 1.25, 1.29, and 1.51) and white blood cell counts (1.00, 1.51, 1.79, and 2.11) with the lowest quartile as the referent group. Similar associations for hemoglobin and hematocrit in the top quartile were also observed. We did not observe any significant difference in the mean of neutrophil count, mean platelet volume (MPV), red cell distribution width, or platelet distribution width among participants with or without metabolic syndrome. Our findings indicate that high levels of major hematological parameters such as hemoglobin, hematocrit, as well as platelet and white blood cell counts could be novel indicators for the development of metabolic syndrome. Copyright © 2017 Diabetes India. Published by Elsevier Ltd. All rights reserved.

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

Regulatory mechanisms of hemoglobin oxygen affinity in acidosis and alkalosis

PubMed Central

Bellingham, A. J.; Detter, J. C.; Lenfant, C.

1971-01-01

The recent reports of the effect of 2,3-diphosphoglycerate (2,3-DPG) on hemoglobin affinity for oxygen suggested that this substance may play a role in man's adaptation to acidosis and alkalosis. A study of the effect of induced acidosis and alkalosis on the oxyhemoglobin dissociation curve of normal man was therefore carried out, and the mechanisms involved in the physiological regulation of hemoglobin oxygen affinity examined. In acute changes of plasma pH there was no alteration in red cell 2,3-DPG content. However, there were changes in hemoglobin oxygen affinity and these correlated with changes in mean corpuscular hemoglobin concentration (MCHC). With maintained acidosis and alkalosis, red cell 2,3-DPG content was altered and correlated with the changes in hemoglobin oxygen affinity. Both of these mechanisms shift the hemoglobin oxygen dissociation curve opposite to the direct pH (Bohr) effect, and providing the rate of pH change is neither too rapid nor too large, they counteract the direct pH effect and the in vivo hemoglobin oxygen affinity remains unchanged. It is also shown that approximately 35% of the change in hemoglobin oxygen affinity resulting from an alteration in red cell 2,3-DPG, is explained by effect of 2,3-DPG on the red cell pH. PMID:5545127

Helicobacter pylori infection in Mongolian gerbils does not initiate hematological diseases

PubMed Central

Xie, Chuan; Xu, Li-Yao; Li, Wei; Yang, Zhen; Lu, Nong-Hua

2014-01-01

AIM: To investigate whether Helicobacter pylori (H. pylori) infection contributes to idiopathic thrombocytopenic purpura (ITP) or iron-deficiency anemia (IDA) onset in gerbils. METHODS: A total of 135 Mongolian gerbils were randomly divided into two groups: an H. pylori infection group and a control group. Both groups were fed the same diet and the same amount of food. Each group was then divided into three subgroups, which were sacrificed at 6, 12, or 18 mo for analysis. At each time point, arterial blood was collected from the abdominal aorta and a complete blood cell count was analyzed in the clinical laboratory in the First Affiliated Hospital of Nanchang University. RESULTS: There were no significant differences in platelet counts (938.00 ± 270.27/L vs 962.95 ± 162.56 × 109/L), red blood cell counts (8.11 ± 1.25/L vs 8.44 ± 1.48 × 1012/L), or hemoglobin levels (136.9 ± 8.76 g/L vs 123.21 ± 18.42 g/L) between the control and the H. pylori groups, respectively, at 18 mo. With the exception of the mean corpuscular volume (MCV), all other indicators, including white blood cell counts, hematocrit, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, red blood cell distribution width, mean platelet volume, platelet distribution width, lymphocyte count, and lymphocyte count percentage, showed no significant differences between the control and H. pylori infection groups at each time point. The MCV in the H. pylori infection group (52.32 f/L ± 2.86 f/L) was significantly lower than the control group (55.63 ± 1.89 f/L) at 18 mo (P = 0.005), though no significant differences were observed at 6 (54.40 ± 2.44 f/L vs 53.30 ± 1.86 f/L) or 12 mo (53.73 ± 2.31 f/L vs 54.80 ± 3.34 f/L). CONCLUSION: A single H. pylori infection is insufficient to cause onset of ITP or IDA and other factors may be required for disease onset. PMID:25232266

[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.

Hemoglobin senses body temperature.

PubMed

Artmann, G M; Digel, Ilya; Zerlin, K F; Maggakis-Kelemen, Ch; Linder, Pt; Porst, D; Kayser, P; Stadler, A M; Dikta, G; Temiz Artmann, A

2009-06-01

When aspirating human red blood cells (RBCs) into 1.3 mum pipettes (DeltaP = -2.3 kPa), a transition from blocking the pipette below a critical temperature T(c) = 36.3 +/- 0.3 degrees C to passing it above the T(c) occurred (micropipette passage transition). With a 1.1 mum pipette no passage was seen which enabled RBC volume measurements also above T(c). With increasing temperature RBCs lost volume significantly faster below than above a T(c) = 36.4 +/- 0.7 (volume transition). Colloid osmotic pressure (COP) measurements of RBCs in autologous plasma (25 degrees C < or = T < or = 39.5 degrees C) showed a T (c) at 37.1 +/- 0.2 degrees C above which the COP rapidly decreased (COP transition). In NMR T(1)-relaxation time measurements, the T(1) of RBCs in autologous plasma changed from a linear (r = 0.99) increment below T(c) = 37 +/- 1 degrees C at a rate of 0.023 s/K into zero slope above T(c) (RBC T(1) transition). An amorphous hemoglobin-water gel formed in the spherical trail, the residual partial sphere of the aspirated RBC. At T(c), a sudden fluidization of the gel occurs. All changes mentioned above happen at a distinct T(c) close to body temperature. The T(c) is moved +0.8 degrees C to higher temperatures when a D(2)O buffer is used. We suggest a mechanism similar to a "glass transition" or a "colloidal phase transition". At T(c), the stabilizing Hb bound water molecules reach a threshold number enabling a partial Hb unfolding. Thus, Hb senses body temperature which must be inscribed in the primary structure of hemoglobin and possibly other proteins.

Blood transfusion in pediatric cardiac surgery.

PubMed

Durandy, Yves

2010-11-01

The aim of the study is to measure the volume of homologous blood needed for one pediatric patient during his hospital stay. Over a 4-month period, all the patients operated upon with a blood prime or requiring blood transfusion during their hospital stay were included in this study.The cardiopulmonary bypass protocol associates a miniaturized bypass circuit, vacuum-assisted venous drainage, and microplegia. The volume of each blood product opened is known and the volume of blood product remaining, following the last transfusion, is measured. Data collected areas follows: patient weight; hemoglobin level before surgery,during bypass, and in intensive care after the last transfusion;time to extubation; and degree of inotropic support.Forty-six patients weighing 5.1 1.5 kg were included in this study. Cardiopulmonary bypass priming volume was 100 mL for patients up to 3.5 kg, 120 mL for patients between 3.6 and 7.5 kg, and 160 mL for patients between 7.6 and 8.6 kg. The volume of blood transfusion was 271 112 mL, hemoglobin level before surgery was 10.3 1.7 g/dL, hemoglobin level during surgery was 11.0 1.5 g/dL, and hemoglobin level after the last transfusion was 12.3 2.4 g/dL. Time to extubation was 12 3.3 h, and inotropic support was enoximone in 37 patients,whereas 6 patients needed enoximone and epinephrine.No patient needed reexploration for bleeding and one patient received a platelet transfusion.The mean blood transfusion volume was equivalent to 60% of the patient’s total blood volume (estimated to be 80 mL/kg).

Hemoglobins, programmed cell death and somatic embryogenesis.

PubMed

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

2013-10-01

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

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.

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.

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.

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.

Prefrontal cerebral blood volume patterns while playing video games--a near-infrared spectroscopy study.

PubMed

Nagamitsu, Shinichiro; Nagano, Miki; Yamashita, Yushiro; Takashima, Sachio; Matsuishi, Toyojiro

2006-06-01

Video game playing is an attractive form of entertainment among school-age children. Although this activity reportedly has many adverse effects on child development, these effects remain controversial. To investigate the effect of video game playing on regional cerebral blood volume, we measured cerebral hemoglobin concentrations using near-infrared spectroscopy in 12 normal volunteers consisting of six children and six adults. A Hitachi Optical Topography system was used to measure hemoglobin changes. For all subjects, the video game Donkey Kong was played on a Game Boy device. After spectroscopic probes were positioned on the scalp near the target brain regions, the participants were asked to play the game for nine periods of 15s each, with 15-s rest intervals between these task periods. Significant increases in bilateral prefrontal total-hemoglobin concentrations were observed in four of the adults during video game playing. On the other hand, significant decreases in bilateral prefrontal total-hemoglobin concentrations were seen in two of the children. A significant positive correlation between mean oxy-hemoglobin changes in the prefrontal region and those in the bilateral motor cortex area was seen in adults. Playing video games gave rise to dynamic changes in cerebral blood volume in both age groups, while the difference in the prefrontal oxygenation patterns suggested an age-dependent utilization of different neural circuits during video game tasks.

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

PubMed Central

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

2013-01-01

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

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.

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

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.

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

PubMed

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

2014-02-01

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

Studies on the alterations in haematological indices, micronuclei induction and pathological marker enzyme activities in Channa punctatus (spotted snakehead) perciformes, channidae exposed to thermal power plant effluent.

PubMed

Javed, Mehjbeen; Ahmad, Irshad; Ahmad, Ajaz; Usmani, Nazura; Ahmad, Masood

2016-01-01

The present study was conducted to assess the toxicity of thermal power plant effluent containing heavy metals (Fe > Cu > Zn > Mn > Ni > Co > Cr) on haematological indices, micronuclei, lobed nuclei and activity of pathological marker enzymes [alkaline phosphatase (ALP), aspartate transferase (AST), alanine transferase (ALT) and creatine kinase (CK)] in Channa punctatus. Total erythrocyte count (-54.52 %), hemoglobin (-36.98 %), packed cell volume (-36.25 %), mean corpuscular hemoglobin concentration (-1.41 %) and oxygen (O2) carrying capacity (-37.04 %) declined significantly over reference fish, however total leukocyte count (+25.43 %), mean corpuscular hemoglobin (+33.52 %) and mean corpuscular volume (+35.49 %) showed elevation. High frequency of micronuclei (1133.3 %) and lobed nuclei (150 %) were observed in exposed fish which may indicate mutagenesis. Activities of pathological marker enzymes ALP, AST, ALT and CK increased significantly in serum of exposed fish. The ratio of ALT: AST in exposed fish was beyond 1 which indicates manifestation of pathological processes. These biomarkers show that fish have macrocytic hypochromic anemia. Leukocytosis showed general defence response against heavy metal toxicity and marker enzymes showed tissue degeneration. In conclusion, thermal power plant effluent has strong potential to induce micronuclei, tissue pathology, making the fish anemic, weak, stressed and vulnerable to diseases.

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

Effect of tranexamic acid on gross hematuria: A pilot randomized clinical trial study.

PubMed

Moharamzadeh, Payman; Ojaghihaghighi, Seyedhossein; Amjadi, Mohsen; Rahmani, Farzad; Farjamnia, Arezoo

2017-12-01

Local forms of the tranexamic acid have been effective in treating many haemorrhagic cases. So that the aim of the current study is to assess the effectiveness of local tranexamic acid in controlling painless hematuria in patients referred to the emergency department. This is a randomized, double-blind clinical trial study, which was conducted on 50 patients with complaints of painless lower urinary tract bleeding during June 2014 and August 2015. The patients were randomly divided into two groups of 25 people each, one group receiving tranexamic acid and the other given a placebo. During bladder irrigation, local tranexamic acid and the placebo were injected into the bladder via Foley catheter. Patients were examined over 24h in terms of the amount of normal saline serum used for irrigation, level of hemoglobin, and blood in urine. In this study it was observed that consumption of tranexamic acid significantly decreased the volume of used serum for bladder irrigation (P=0.041) and the microscopic status of urine decreased significantly in terms of the hematuria after 24h (P=0.026). However, the rate of packed cell transfusion and drop in hemoglobin levels showed no significant difference in both groups of patients (P˃0.05). The results of this study showed that tranexamic acid could significantly reduce the volume of required serum for bladder irrigation to clear urine, but it had no significant effect on the drop in serum hemoglobin levels. Copyright © 2017 Elsevier Inc. All rights reserved.

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

PubMed

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

1999-10-01

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

Granulocyte-colony stimulating factor administration among hemoglobin S trait donors: A single center experience from the Eastern Mediterranean region.

PubMed

Gereklioglu, Cigdem; Asma, Suheyl; Korur, Aslı; Tepebaşı, Songul; Aytan, Pelin; Yeral, Mahmut; Kozanoglu, Ilknur; Boga, Can; Ozdogu, Hakan

2018-02-01

Assessment of Hemoglobin S trait donors has gained importance together with the increased allogeneic peripheral stem cell transplant activity for sickle cell disease in the regions where the disease is prevalent. Outcomes of Granulocyte-Colony Stimulating Factor (G-CSF) administration are obscure for hemoglobin S trait donors. This study aims at investigating the incidence of hemoglobin S carrier status and outcomes of G-CSF administration among donors who live in Eastern Mediterranean region. The cross-sectional, single-center cohort study was performed with 147 donors between January 2013 and March 2017. Prevalence of hemoglobin S trait was estimated and subjects with or without Hemogobin S trait were compared with regard to stem cell characteristics, early and late clinical outcomes after G-CSF administration. Eleven out of 147 donors (7.48%) were found as hemoglobin S trait. G-CSF administration was successfully completed and yielded good harvesting results in hemoglobin S trait donors. No statistically significant difference was found between groups with regard to early and late side effects, stem cell characteristics. Blood pressures and QTc values were within normal ranges in both groups. Groups were similar with regard to CD34 values. G-CSF seems safe in hemoglobin S trait donors. Their being eligible as donors would increase the chance of the patients for allogeneic stem cell transplantation in high prevalence regions. Further studies are required to reveal the safety profile of G-SCF in hemoglobin S carriers in different regions. © 2017 Wiley Periodicals, Inc.

Single-cell measurement of red blood cell oxygen affinity.

PubMed

Di Caprio, Giuseppe; Stokes, Chris; Higgins, John M; Schonbrun, Ethan

2015-08-11

Oxygen is transported throughout the body by hemoglobin (Hb) in red blood cells (RBCs). Although the oxygen affinity of blood is well-understood and routinely assessed in patients by pulse oximetry, variability at the single-cell level has not been previously measured. In contrast, single-cell measurements of RBC volume and Hb concentration are taken millions of times per day by clinical hematology analyzers, and they are important factors in determining the health of the hematologic system. To better understand the variability and determinants of oxygen affinity on a cellular level, we have developed a system that quantifies the oxygen saturation, cell volume, and Hb concentration for individual RBCs in high throughput. We find that the variability in single-cell saturation peaks at an oxygen partial pressure of 2.9%, which corresponds to the maximum slope of the oxygen-Hb dissociation curve. In addition, single-cell oxygen affinity is positively correlated with Hb concentration but independent of osmolarity, which suggests variation in the Hb to 2,3-diphosphoglycerate (2-3 DPG) ratio on a cellular level. By quantifying the functional behavior of a cellular population, our system adds a dimension to blood cell analysis and other measurements of single-cell variability.

Single-cell measurement of red blood cell oxygen affinity

PubMed Central

Di Caprio, Giuseppe; Stokes, Chris; Higgins, John M.; Schonbrun, Ethan

2015-01-01

Oxygen is transported throughout the body by hemoglobin (Hb) in red blood cells (RBCs). Although the oxygen affinity of blood is well-understood and routinely assessed in patients by pulse oximetry, variability at the single-cell level has not been previously measured. In contrast, single-cell measurements of RBC volume and Hb concentration are taken millions of times per day by clinical hematology analyzers, and they are important factors in determining the health of the hematologic system. To better understand the variability and determinants of oxygen affinity on a cellular level, we have developed a system that quantifies the oxygen saturation, cell volume, and Hb concentration for individual RBCs in high throughput. We find that the variability in single-cell saturation peaks at an oxygen partial pressure of 2.9%, which corresponds to the maximum slope of the oxygen–Hb dissociation curve. In addition, single-cell oxygen affinity is positively correlated with Hb concentration but independent of osmolarity, which suggests variation in the Hb to 2,3-diphosphoglycerate (2–3 DPG) ratio on a cellular level. By quantifying the functional behavior of a cellular population, our system adds a dimension to blood cell analysis and other measurements of single-cell variability. PMID:26216973

Hypervolemia and plasma vasopressin response during water immersion in men

NASA Technical Reports Server (NTRS)

Greenleaf, J. E.; Morse, J. T.; Barnes, P. R.; Silver, J.; Keil, L. C.

1983-01-01

Immersion studies were performed on seven mildly dehydrated male subjects to examine the effect of suppression of plasma vasopressin (PVP) on diuresis in water immersion. The water was kept at close to 34.5 C and the subjects remained in the water for 4 hr after sitting for 2 hr. Na and K levels in the serum and urine were analyzed, as were osmolality, red blood cell count, renin activity, total protein, albumin amounts, hematocrit, and hemoglobin. Plasma volume was monitored from samples drawn at specified intervals during immersion. The plasma volume increased significantly 30 min after immersion, but no PVP was observed. The dehydration induced elevated serum osmotic concentrations. It is concluded that the hydration condition before immersion and the volume of fluid intake during immersion affects the hemodilution during immersion.

Correlation of low levels of nitrite and high levels of fetal hemoglobin in patients with sickle cell disease at baseline

PubMed Central

Elias, Darcielle Bruna Dias; Rocha, Lilianne Brito da Silva; Cavalcante, Maritza Barbosa; Pedrosa, Alano Martins; Justino, Izabel Cristina Bandeira; Gonçalves, Romélia Pinheiro

2012-01-01

Background Sickle cell disease is a hemoglobinopathy characterized by hemolytic anemia, increased susceptibility to infections and recurrent vaso-occlusive crises that reduces the quality of life of sufferers. Objective To evaluate the correlation of the levels of lactate dehydrogenase, malonaldehyde and nitrite to fetal hemoglobin in patients with sickle cell disease not under treatment with hydroxyurea in outpatients at a university hospital in Fortaleza, Ceará, Brazil. Methods Forty-four patients diagnosed with sickle cell disease were enrolled at baseline. Diagnosis was confirmed by evaluating the beta globin gene using polymerase chain reaction-restriction fragment length polymorphism. The concentration of fetal hemoglobin was obtained by high-performance liquid chromatography. Serum levels of nitrite, malonaldehyde and lactate dehydrogenase were measured by biochemical methods. Results Significantly higher levels of lactate dehydrogenase, nitrite and malonaldehyde were observed in patients with sickle cell disease compared to a control group. The study of the correlation between fetal hemoglobin levels and these variables showed a negative correlation with nitrite levels. No correlation was found between fetal hemoglobin and malonaldehyde or lactate dehydrogenase. When the study population was stratified according to fetal hemoglobin levels, a decrease in the levels of nitrite was observed with higher levels of fetal hemoglobin (p-value = 0.0415). Conclusion The results show that, similar to fetal hemoglobin levels, the concentration of nitrite can predict the clinical course of the disease, but should not be used alone as a modulator of prognosis in patients with sickle cell disease. PMID:23049438

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).

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.

Hematological and metabolic responses to training in racing sled dogs fed diets containing medium, low, or zero carbohydrate.

PubMed

Kronfeld, D S; Hammel, E P; Ramberg, C F; Dunlap, H L

1977-03-01

In a 28 week study, 18 racing sled dogs were trained to maximal fitness in 12 weeks, sustained through a racing season of 12 weeks, followed by gradual of training of 4 weeks. The dogs were fed a predominantly cereal diet prior to the study; experimental diets containing more chicken and meat by products were introduced from the 2nd to the 4th week of training. On an energy basis, the diets contained protein, fat, and carbohydrate in the proportions of 39:61:0 (diet A), 32:45:23 (diet B), and 28:34:38 (diet C). Blood samples were taken at rest just before the start of training, at 6, 12,24 and 28 weeks; 33 variables were measured on most samples. The results were subjected to analysis of variance. No adverse effects were observed in dogs fed the extreme diet A. Significant relationships to training were shown by serum glutamic oxaloacetic transaminase, creatinine, packed cell volume, calcium, hemoglobin, and globulin. Serum cholesterol concentration increased with the introduction of the higher protein-fat diets; the high concentrations attenuated with time but rose again when training was abated. Dogs on diet A maintained higher serum concentrations of albumin, calcium, magnesium, and free fatty acids during the racing season than did dogs fed diets B or C. They also exhibited the greatest increases in red cell count, hemoglobin concentration, and packed cell volume during training. High values of red cell indices were not sustained through the racing season in dogs fed diet C. In addition to attributes already widely appreciated, viz. a higher energy density an digestibility, the carbohydrate-free, high-fat diet A appeared to confer advantages for prolonged strenuous running in terms of certain metabolic responses to training.

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.

The accuracy of noninvasive hemoglobin monitoring using the radical-7 pulse CO-Oximeter in children undergoing neurosurgery.

PubMed

Park, Yong-Hee; Lee, Ji-Hyun; Song, Hyun-Gul; Byon, Hyo-Jin; Kim, Hee-Soo; Kim, Jin-Tae

2012-12-01

The most common method for determining the hemoglobin concentration is to draw blood from a patient. However, the Radical-7 Pulse CO-Oximeter (Masimo Corporation, Irvine, CA) can noninvasively provide continuous hemoglobin concentration (SpHb). In our study we compared noninvasive measurements of SpHb with simultaneous laboratory measurements of total hemoglobin in arterial blood samples taken from children (tHb). Arterial blood samples were analyzed using a laboratory CO-oximeter, and SpHb was simultaneously recorded in pediatric patients undergoing neurosurgery. When patients met the criteria for hypovolemia, 10 mL/kg of colloids or red blood cells were administered over 10 minutes. SpHb and tHb data were collected before and after intravascular volume resuscitation. The relationship between SpHb and tHb was assessed using a 4-quadrant plot, linear regression, mixed-effect model, and modified Bland-Altman analyses. One hundred nineteen paired samples were analyzed. The correlation coefficient between SpHb and tHb was 0.53 (P < 0.001), whereas that of change in SpHb versus change in tHb was 0.75 (P < 0.001). The average difference (bias) between tHb and SpHb was 0.90 g/dL (95% confidence interval [CI], 0.48-1.32 g/dL) and 1 standard deviation of the difference (sd) was 1.35 g/dL. The concordance rate (a measure of the number of data points that are in 1 of the 2 quadrants of agreement) determined using a 4-quadrant plot was 93%. The correlation coefficient between SpHb and tHb after intravascular volume resuscitation was 0.58 (P < 0.001), whereas that of changes in SpHb and tHb was 0.87 (P < 0.001). The bias immediately after volume resuscitation was 1.18 g/dL (95% CI, 0.81-1.55 g/dL), and sd was 1.28 g/dL with a concordance rate of 94.4%. The bias was -0.03 g/dL when tHb was ≥11 g/dL, which was significantly lower in comparison with biases when tHb <9 g/dL (1.24 g/dL) and tHb was 9-11 g/dL (1.17 g/dL) (P = 0.004). The Radical-7 Pulse CO-Oximeter can be useful as a trend monitor in children during surgery even immediately after intravascular volume expanders are administered. However, it is advisable to confirm the baseline hemoglobin level and to consider the influence of tHb level on the bias. In addition, one should be cautious with regard to using SpHb alone when making transfusion decisions.

Diffuse Reflectance Spectroscopy (DRS) of radiation-induced re-oxygenation in sensitive and resistant head and neck tumor xenografts

NASA Astrophysics Data System (ADS)

Dadgar, Sina; Rodríguez Troncoso, Joel; Rajaram, Narasimhan

2018-02-01

Currently, anatomical assessment of tumor volume performed several weeks after completion of treatment is the clinical standard to determine whether a cancer patient has responded to a treatment. However, functional changes within the tumor could potentially provide information regarding treatment resistance or response much earlier than anatomical changes. We have used diffuse reflectance spectroscopy to assess the short and long-term re-oxygenation kinetics of a human head and neck squamous cell carcinoma xenografts in response to radiation therapy. First, we injected UM-SCC-22B cell line into the flank of 50 mice to grow xenografts. Once the tumor volume reached 200 mm3 (designated as Day 1), the mice were distributed into radiation and control groups. Members of radiation group underwent a clinical dose of radiation of 2 Gy/day on Days 1, 4, 7, and 10 for a cumulative dose of 8 Gy. DRS spectra of these tumors were collected for 14 days during and after therapy, and the collected spectra of each tumor were converted to its optical properties using a lookup table-base inverse model. We found statistically significant differences in tumor growth rate between two groups which is in indication of the sensitivity of this cell line to radiation. We further acquired significantly different contents of hemoglobin and scattering magnitude and size in two groups. The scattering has previously been associated with necrosis. We furthermore found significantly different time-dependent changes in vascular oxygenation and tumor hemoglobin concentration in post-radiation days.

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

Plasma volume during stress in man - Osmolality and red cell volume

NASA Technical Reports Server (NTRS)

Greenleaf, J. E.; Convertino, V. A.; Mangseth, G. R.

1979-01-01

The purpose was (1) to test the hypothesis that in man there is a range of plasma osmolality within which the red cell volume (RCV) and mean corpuscular volume (MCV) remain essentially constant and (2) to determine the upper limit of this range. During a variety of stresses - submaximal and maximal exercise, heat and altitude exposure, +Gz acceleration, and tilting - changes in plasma osmolality between -1 and +13 mosmol/kg resulted in essentially no change in the regression of percent change in plasma volume (PV) calculated from a change in hematocrit (Hct) on that calculated from a change in Hct + hemoglobin (Hb), i.e., the RCV and MCV were constant. Factors that do not influence RCV are the level of metabolism, heat exposure at rest, and short-term orthostasis (heat-to-foot acceleration). Factors that may influence RCV are exposure to high altitude and long-term orthostasis (head-up tilting). Factors that definitely influence RCV are prior dehydration and extended periods of stress. Thus, either the Hct or the Hct + Hb equations can be used to calculate percent changes in PV under short-term periods of stress when the change in plasma osmolality is less than 13 mosmol/kg.

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.

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

Initial Assessment and Resuscitation in Nonvariceal Upper Gastrointestinal Bleeding.

PubMed

Simon, Tracey G; Travis, Anne C; Saltzman, John R

2015-07-01

Acute nonvariceal upper gastrointestinal bleeding remains an important cause of hospital admission with an associated mortality of 2-14%. Initial patient evaluation includes rapid hemodynamic assessment, large-bore intravenous catheter insertion and volume resuscitation. A hemoglobin transfusion threshold of 7 g/dL is recommended, and packed red blood cell transfusion may be necessary to restore intravascular volume and improve tissue perfusion. Patients should be risk stratified into low- and high-risk categories, using validated prognostic scoring systems such as the Glasgow-Blatchford, AIMS65 or Rockall scores. Effective early management of acute, nonvariceal upper gastrointestinal hemorrhage is critical for improving patient outcomes. Copyright © 2015 Elsevier Inc. All rights reserved.

Detoxifying effect of Nelumbo nucifera and Aegle marmelos on hematological parameters of Common Carp (Cyprinus carpio L.)

PubMed Central

Vinodhini, Rajamanickam

2010-01-01

The objective of this study was to investigate the efficacy of Nelumbo nucifera and Aegle marmelos on common carp exposed to sub-lethal concentrations of combined heavy metals (5 ppm) under laboratory conditions. The fish were treated with Nelumbo nucifera (500 mg/kg bwt) and Aegle marmelos (500 mg/kgbwt) for 30 days as a dietary supplement. The blood biochemical parameters of the fish were evaluated by analyzing the level of red blood cells (RBC), packed cell volume (PCV), hemoglobin concentration, glucose, cholesterol, iron and copper. The findings of the present investigation showed significant increase in hemoglobin (p<0.001), RBC (p<0.01) and PCV (p<0.01) of herbal drug-treated groups compared with metal-exposed fish. Conversely, glucose and cholesterol level in blood of common carp showed significant reduction compared with heavy-metal-exposed groups. All the values measured in Nelumbo nucifera and Aegle marmelos treated fish were restored comparably to control fish. Our results confirmed that Nelumbo nucifera and Aegle marmelos provide a detoxification mechanism for heavy metals in common carp. PMID:21331178

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 ...

One-step genetic correction of hemoglobin E/beta-thalassemia patient-derived iPSCs by the CRISPR/Cas9 system.

PubMed

Wattanapanitch, Methichit; Damkham, Nattaya; Potirat, Ponthip; Trakarnsanga, Kongtana; Janan, Montira; U-Pratya, Yaowalak; Kheolamai, Pakpoom; Klincumhom, Nuttha; Issaragrisil, Surapol

2018-02-26

Thalassemia is the most common genetic disease worldwide; those with severe disease require lifelong blood transfusion and iron chelation therapy. The definitive cure for thalassemia is allogeneic hematopoietic stem cell transplantation, which is limited due to lack of HLA-matched donors and the risk of post-transplant complications. Induced pluripotent stem cell (iPSC) technology offers prospects for autologous cell-based therapy which could avoid the immunological problems. We now report genetic correction of the beta hemoglobin (HBB) gene in iPSCs derived from a patient with a double heterozygote for hemoglobin E and β-thalassemia (HbE/β-thalassemia), the most common thalassemia syndrome in Thailand and Southeast Asia. We used the CRISPR/Cas9 system to target the hemoglobin E mutation from one allele of the HBB gene by homology-directed repair with a single-stranded DNA oligonucleotide template. DNA sequences of the corrected iPSCs were validated by Sanger sequencing. The corrected clones were differentiated into hematopoietic progenitor and erythroid cells to confirm their multilineage differentiation potential and hemoglobin expression. The hemoglobin E mutation of HbE/β-thalassemia iPSCs was seamlessly corrected by the CRISPR/Cas9 system. The corrected clones were differentiated into hematopoietic progenitor cells under feeder-free and OP9 coculture systems. These progenitor cells were further expanded in erythroid liquid culture system and developed into erythroid cells that expressed mature HBB gene and HBB protein. Our study provides a strategy to correct hemoglobin E mutation in one step and these corrected iPSCs can be differentiated into hematopoietic stem cells to be used for autologous transplantation in patients with HbE/β-thalassemia in the future.

MO-G-BRF-06: Radiotherapy and Prompt Oxygen Dynamics

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

Kissick, M; Campos, D; Adamson, E

Purpose: Adaptive radiotherapy requires a knowledge of the changing local tumor oxygen concentrations for times on the order of the treatment time, a time scale far shorter than cell death and proliferation. This knowledge will be needed to guide hypofractionated radiotherapy. Methods: A diffuse optical probe system was developed to spatially average over the whole interior of athymic Sprague Dawley nude mouse xenografts of human head and neck cancers. The blood volume and hemoglobin saturation was measured in real time. The quantities were measured with spectral fitting before and after 10 Gy of radiation is applied. An MRI BOLD scanmore » is acquired before and after 10 Gy that measures regional changes in R2* which is inversely proportional to oxygen availability. Simulations were performed to fit the blood oxygen dynamics and infer changes in hypoxia within the tumor. Results: The optical probe measured nearly constant blood volume and a significant drop in hemoglobin saturation of about 30% after 10 Gy over the time scale of less than 30 minutes. The averaged R2* within the tumor volume increased by 15% after the 10 Gy dose, which is consistent with the optical results. The simulations and experiments support likely dynamic metabolic changes and/or fast vasoconstrictive signals are occurring that change the oxygen concentrations significantly, but not cell death or proliferation. Conclusion: Significant oxygen changes were observed to occur within 30 minutes, coinciding with the treatment time scale. This dynamic is very important for patient specific adaptive therapy. For hypofractionated therapy, the local instantaneous oxygen content is likely the most important variable to control. The invention of a bedside device for the purpose of measuring the instantaneous response to large radiation doses would be an important step to future improvements in outcome.« less

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.

Subchronic Toxicity Studies on 1,3,5-Trinitrobenzene, 1,3- Dinitrobenzene, and Tetryl in Rats. Subchronic Toxicity Evaluation of 1,3,5- Trinitrobenzene in Fischer 344 Rats

DTIC Science & Technology

1994-05-01

cton ofMO,,natt. ’"An saqe jr~n ’edw tc.ngin o...rm to Wailoqto. HeCdos11#, ¶ n1e i Oueftoc D or.,e fwaft at~on OOWctl~t~ and AeoOat. 12 11 J~flfflOI 0S...controls in both sexes.3 14. SUBJECT TERMS 115 . NUMBER OF PAGES 16. PRICE CODE 17. SECURITv CLASSIFICATION 13. SECURITY CLASSIFICATION 19. SECURITY...NJ). Total red and white blood cell counts, platelet count, differential leukocyte count, hemoglobin, and packed cell volume were measured and

Prevalence of Anemia and Hemoglobin Disorders Among School Children in Myanmar.

PubMed

Wah, Saw Thu; Yi, Yoon Shwe; Khin, Aye Aye; Plabplueng, Chotiros; Nuchnoi, Pornlada

2017-01-01

The prevalence of anemia is high in the population of Myanmar and hypochromic microcytic anemia (HMA) is predominant. The objective of our study was to determine the prevalence of anemia and causes of HMA among school children. A cross-sectional study was conducted on 239 children from Thanlyin and Insein Townships, Yangon Region, Myanmar. Complete blood count (CBC) and blood film morphology was examined on venous blood samples. Hypochromic microcytic anemia cases were subsequently analyzed for serum ferritin and cellulose acetate hemoglobin (Hb) electrophoresis. The prevalence of anemia was 46.4%; 27.6% had mild, while 18.8% had moderate anemia, and no case of severe anemia was detected. The mean Hb concentration was 11.7 ± 0.9 g/dL. The younger age group (8-11 years) had a significantly higher prevalence of anemia than the older age group (12-15 years) (p = 0.029). Blood film morphology revealed a 50.6% red blood cell (RBC) disorder; HMA was the most common type (70.2%). Out of 85 children with HMA, three children (3.5%) had iron deficiency and all had comorbidity with Hb AE (β A /β E ) (Hb E trait). Hemoglobin electrophoresis illustrated that Hb AA (β A /β A ) (31, 36.5%) and Hb AE (β A /β E ) trait (31, 36.5%) were the most common types followed by β-thalassemia (β-thal) trait (19, 22.3%) and Hb EE (β E /β E ) (homozygous Hb E; HBB: c.79G>A) (three, 3.5%). Hematocrit [or packed cell volume (PCV)], mean corpuscular volume (MCV), mean corpuscular Hb (MCH) and mean corpuscular Hb concentration (MCHC), showed a significant difference between Hb AE, Hb EE and β-thal trait (p = 0.029, 0.023, 0.015 and 0.01, respectively). Our findings will provide valuable information for the management of anemia in the Myanmar school-age population.

Static structures and dynamics of hemoglobin vesicle (HBV) developed as a transfusion alternative.

PubMed

Sato, Takaaki; Sakai, Hiromi; Sou, Keitaro; Medebach, Martin; Glatter, Otto; Tsuchida, Eishun

2009-06-18

Hemoglobin vesicle (HbV) is an artificial oxygen carrier that encapsulates solution of purified and highly concentrated (ca. 38 g dL(-1)) human hemoglobin. Its exceptionally high concentration as a liposomal product (ca. 40% volume fraction) achieves an oxygen-carrying capacity comparable to that of blood. We use small-angle X-ray scattering (SAXS) and dynamic light scattering (DLS) to investigate the hierarchical structures and dynamics of HbVs in concentrated suspensions. SAXS data revealed unilamellar shell structure and internal density profile of the artificial cell membrane for Hb encapsulation. The SAXS intensity of HbV at scattering vector q > 0.5 nm(-1) manifests dissolution states of the encapsulated Hbs in the inner aqueous phase of the vesicle having ca. 240 nm diameter. The peak position as well as the height and width of static structure factor of Hb before and after encapsulation are almost identical, demonstrating the preserved protein-protein interactions in the confined space. To overcome multiple scattering from turbid samples, we employed thin layer-cell DLS combined with the so-called bruteforce and echo techniques, which allows us to observe collective diffusion dynamics of HbVs without dilution. A pronounced slowdown of the HbV diffusion and eventual emergence of dynamically arrested state in the presence of high-concentration plasma substitutes (water-soluble polymers), such as dextran, modified fluid gelatin, and hydroxylethyl starch, can be explained by depletion interaction. A significantly weaker effect of recombinant human serum albumin on HbV flocculation and viscosity enhancement than those induced by other polymers is clearly attributed to the specificity as a protein; its compact structure efficiently reduces the reservoir polymer volume fraction that determines the depth of the attractive potential between HbVs. These phenomena are technically essential for controlling the suspension rheology, which is advantageous for versatile clinical applications.

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.

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.

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.

[The physiologic significance of 2,3-diphosphoglycerate and changes in its erythrocyte levels in an experiment].

PubMed

Béder, I; Orgonásová, M; Brozman, B; Horecký, J; Mataseje, A

1990-05-01

The regulatory effect of 2,3-DPG on oxygen transport and binding to hemoglobin was analyzed. Under conditions of substitution hemodilution by isooncotic 3.4% Rheodextran (Spofa), changes in the content of 2,3-DPG in arterial and venous blood were enzymatically determined over several days. Reference values of 2,3-DPG were obtained in the studied series of dogs (2.05 +/- 0.74 x 10(-6) mol.ml-1 in whole blood 4.69 +/- 1.52 x 10(-6) mol.g-1 of erythrocyte volume, and 13.39 +/- 2.82 x 10(-6) mol.ml-1 of hemoglobin). In anesthetized animals the content of 2,3-DPG in arterial blood was significantly higher (6.28 +/- 0.84 x 10(-6) mol.ml-1 of erythrocyte volume) than in venous blood (6.01 +/- 0.80 x 10(-6) mol.ml-1 of erythrocyte volume). At substitution hemodilution the 2,3-DPG content in erythrocytes of venous blood decreased from 5.46 +/- 0.67 to 4.97 +/- 1.31 x 10(-6) mol.ml-1 of erythrocyte volume. The subsequent increase to 6.04 +/- 0.71 x 10(-6) mol.ml-1 of erythrocyte volume was achieved by nonlinear increase over the following days, at persisting low hemoglobin content in blood.

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

PubMed

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

2013-01-01

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

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

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…

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 ...

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 ...

21 CFR 864.5300 - Red cell indices device.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Red cell indices device. 864.5300 Section 864.5300....5300 Red cell indices device. (a) Identification. A red cell indices device, usually part of a larger... corpuscular hemoglobin (MCH), and the mean corpuscular hemoglobin concentration (MCHC). The red cell indices...

21 CFR 864.5300 - Red cell indices device.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Red cell indices device. 864.5300 Section 864.5300....5300 Red cell indices device. (a) Identification. A red cell indices device, usually part of a larger... corpuscular hemoglobin (MCH), and the mean corpuscular hemoglobin concentration (MCHC). The red cell indices...

21 CFR 864.5300 - Red cell indices device.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Red cell indices device. 864.5300 Section 864.5300....5300 Red cell indices device. (a) Identification. A red cell indices device, usually part of a larger... corpuscular hemoglobin (MCH), and the mean corpuscular hemoglobin concentration (MCHC). The red cell indices...

21 CFR 864.5300 - Red cell indices device.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Red cell indices device. 864.5300 Section 864.5300....5300 Red cell indices device. (a) Identification. A red cell indices device, usually part of a larger... corpuscular hemoglobin (MCH), and the mean corpuscular hemoglobin concentration (MCHC). The red cell indices...

21 CFR 864.5300 - Red cell indices device.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Red cell indices device. 864.5300 Section 864.5300....5300 Red cell indices device. (a) Identification. A red cell indices device, usually part of a larger... corpuscular hemoglobin (MCH), and the mean corpuscular hemoglobin concentration (MCHC). The red cell indices...

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 ...

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

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.

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.

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...

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

PubMed

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

2017-02-01

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

Smart fast blood counting of trace volumes of body fluids from various mammalian species using a compact custom-built microscope cytometer (Conference Presentation)

NASA Astrophysics Data System (ADS)

Smith, Zachary J.; Gao, Tingjuan; Lin, Tzu-Yin; Carrade-Holt, Danielle; Lane, Stephen M.; Matthews, Dennis L.; Dwyre, Denis M.; Wachsmann-Hogiu, Sebastian

2016-03-01

Cell counting in human body fluids such as blood, urine, and CSF is a critical step in the diagnostic process for many diseases. Current automated methods for cell counting are based on flow cytometry systems. However, these automated methods are bulky, costly, require significant user expertise, and are not well suited to counting cells in fluids other than blood. Therefore, their use is limited to large central laboratories that process enough volume of blood to recoup the significant capital investment these instruments require. We present in this talk a combination of a (1) low-cost microscope system, (2) simple sample preparation method, and (3) fully automated analysis designed for providing cell counts in blood and body fluids. We show results on both humans and companion and farm animals, showing that accurate red cell, white cell, and platelet counts, as well as hemoglobin concentration, can be accurately obtained in blood, as well as a 3-part white cell differential in human samples. We can also accurately count red and white cells in body fluids with a limit of detection ~3 orders of magnitude smaller than current automated instruments. This method uses less than 1 microliter of blood, and less than 5 microliters of body fluids to make its measurements, making it highly compatible with finger-stick style collections, as well as appropriate for small animals such as laboratory mice where larger volume blood collections are dangerous to the animal's health.

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

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.

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.

Effect of gamma radiation on the growth, survival, hematology and histological parameters of rainbow trout (Oncorhynchus mykiss) larvae.

PubMed

Oujifard, Amin; Amiri, Roghayeh; Shahhosseini, Gholamreza; Davoodi, Reza; Moghaddam, Jamshid Amiri

2015-08-01

Effects of low (1, 2.5 and 5Gy) and high doses (10, 20 and 40Gy) of gamma radiation were examined on the growth, survival, blood parameters and morphological changes of the intestines of rainbow trout (Oncorhynchus mykiss) larvae (103±20mg) after 12 weeks of exposure. Negative effects of gamma radiation on growth and survival were observed as radiation level and time increased. Changes were well documented at 10 and 20Gy. All the fish were dead at the dose of 40Gy. In all the treatments, levels of red blood cells (RBC), hematocrit (HCT) and hemoglobin (HB) were significantly (P<0.05) declined as the irradiation levels increased, whereas the amount of mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) did not change. No significant differences (P>0.05) were found in the levels of white blood cells (WBC), lymphocytes and monocytes. Destruction of the intestinal epithelium cells was indicated as the irradiation levels increased to 1Gy and above. The highest levels of growth, survival, specific growth rate (SGR), condition factor (CF) and protein efficiency rate (PER) were obtained in the control treatment. The results showed that gamma rays can be a potential means for damaging rainbow trout cells. Copyright © 2015 Elsevier B.V. All rights reserved.

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 ...

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.

Intravascular hemolysis and the pathophysiology of sickle cell disease

PubMed Central

Kato, Gregory J.; Steinberg, Martin H.; Gladwin, Mark T.

2017-01-01

Hemolysis is a fundamental feature of sickle cell anemia that contributes to its pathophysiology and phenotypic variability. Decompartmentalized hemoglobin, arginase 1, asymmetric dimethylarginine, and adenine nucleotides are all products of hemolysis that promote vasomotor dysfunction, proliferative vasculopathy, and a multitude of clinical complications of pulmonary and systemic vasculopathy, including pulmonary hypertension, leg ulcers, priapism, chronic kidney disease, and large-artery ischemic stroke. Nitric oxide (NO) is inactivated by cell-free hemoglobin in a dioxygenation reaction that also oxidizes hemoglobin to methemoglobin, a non–oxygen-binding form of hemoglobin that readily loses heme. Circulating hemoglobin and heme represent erythrocytic danger-associated molecular pattern (eDAMP) molecules, which activate the innate immune system and endothelium to an inflammatory, proadhesive state that promotes sickle vaso-occlusion and acute lung injury in murine models of sickle cell disease. Intravascular hemolysis can impair NO bioavailability and cause oxidative stress, altering redox balance and amplifying physiological processes that govern blood flow, hemostasis, inflammation, and angiogenesis. These pathological responses promote regional vasoconstriction and subsequent blood vessel remodeling. Thus, intravascular hemolysis represents an intrinsic mechanism for human vascular disease that manifests clinical complications in sickle cell disease and other chronic hereditary or acquired hemolytic anemias. PMID:28248201

Visualizing red blood cell sickling and the effects of inhibition of sphingosine kinase 1 using soft X-ray tomography

DOE PAGES

Darrow, Michele C.; Zhang, Yujin; Cinquin, Bertrand P.; ...

2016-08-09

Sickle cell disease is a destructive genetic disorder characterized by the formation of fibrils of deoxygenated hemoglobin, leading to the red blood cell (RBC) morphology changes that underlie the clinical manifestations of this disease. Here, using cryogenic soft X-ray tomography (SXT), we characterized the morphology of sickled RBCs in terms of volume and the number of protrusions per cell. We were able to identify statistically a relationship between the number of protrusions and the volume of the cell, which is known to correlate to the severity of sickling. This structural polymorphism allows for the classification of the stages of themore » sickling process. Recent studies have shown that elevated sphingosine kinase 1 (Sphk1)-mediated sphingosine 1-phosphate production contributes to sickling. Here, we further demonstrate that compound 5C, an inhibitor of Sphk1, has anti-sickling properties. Additionally, the variation in cellular morphology upon treatment suggests that this drug acts to delay the sickling process. SXT is an effective tool that can be used to identify the morphology of the sickling process and assess the effectiveness of potential therapeutics.« less

Visualizing red blood cell sickling and the effects of inhibition of sphingosine kinase 1 using soft X-ray tomography

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

Darrow, Michele C.; Zhang, Yujin; Cinquin, Bertrand P.

Sickle cell disease is a destructive genetic disorder characterized by the formation of fibrils of deoxygenated hemoglobin, leading to the red blood cell (RBC) morphology changes that underlie the clinical manifestations of this disease. Here, using cryogenic soft X-ray tomography (SXT), we characterized the morphology of sickled RBCs in terms of volume and the number of protrusions per cell. We were able to identify statistically a relationship between the number of protrusions and the volume of the cell, which is known to correlate to the severity of sickling. This structural polymorphism allows for the classification of the stages of themore » sickling process. Recent studies have shown that elevated sphingosine kinase 1 (Sphk1)-mediated sphingosine 1-phosphate production contributes to sickling. Here, we further demonstrate that compound 5C, an inhibitor of Sphk1, has anti-sickling properties. Additionally, the variation in cellular morphology upon treatment suggests that this drug acts to delay the sickling process. SXT is an effective tool that can be used to identify the morphology of the sickling process and assess the effectiveness of potential therapeutics.« less

Comparison of Blood Loss in Laser Lipolysis vs Traditional Liposuction.

PubMed

Abdelaal, Mohammed Mahmoud; Aboelatta, Yasser Abdallah

2014-08-01

Laser-assisted liposuction has been associated with reduced blood loss. However, this clinical finding has not been evaluated objectively. In this study, the authors objectively estimated the blood loss volume associated with laser lipolysis vs traditional liposuction in various anatomic regions. In this prospective study, 56 patients underwent equal amounts of traditional and laser-assisted liposuction at 2 contralateral anatomic sites. Blood loss volumes were calculated from the lipoaspirates by measuring hemoglobin and red blood cell content. The data were analyzed statistically with repeated-measures analysis of variance and the Mann-Whitney U test. Laser lipolysis can reduce blood loss by more than 50% compared with traditional liposuction. Laser lipolysis resulted in significant reductions in mean blood loss volumes in the abdomen, flanks, back, and breast. The authors provide objective evidence that laser lipolysis significantly reduces blood loss compared with traditional liposuction. 3. © 2014 The American Society for Aesthetic Plastic Surgery, Inc.

Physiological responses of mules on prolonged exposure to high altitude (3 650 m)

NASA Astrophysics Data System (ADS)

Riar, S. S.; Shankar Bhat, K.; Sen Gupta, J.

1982-06-01

Eight healthy male animals were inducted and kept for 2 1/2 years at 3 650 m altitude and subjected to normal work schedules. Physiological measurements viz. heart rate, blood pressure, minute ventilation, oxygen consumption, respiration rate, hemoglobin, packed cell haematocrit volume and eosinophil count were made on these animals at periodic intervals. On acute induction to an altitude of 3 650 m these animals demonstrated a sudden increase in tidal volume, a decrease in Rf and no change in VE, suggesting a decreased dead space/tidal volume ratio at altitude. However, all these changes stabilised within 3 weeks but on prolongation of stay, the physical state of these animals was adversely affected. The respiratory adjustments occurring on return to sea level appear to be a response to thermal stress. The initial increase in heart rate and blood pressure stabilised by the 2nd week.

Photoacoustic spectroscopic imaging of intra-tumor heterogeneity and molecular identification

NASA Astrophysics Data System (ADS)

Stantz, Keith M.; Liu, Bo; Cao, Minsong; Reinecke, Dan; Miller, Kathy; Kruger, Robert

2006-02-01

Purpose. To evaluate photoacoustic spectroscopy as a potential imaging modality capable of measuring intra-tumor heterogeneity and spectral features associated with hemoglobin and the molecular probe indocyanine green (ICG). Material and Methods. Immune deficient mice were injected with wildtype and VEGF enhanced MCF-7 breast cancer cells or SKOV3x ovarian cancer cells, which were allowed to grow to a size of 6-12 mm in diameter. Two mice were imaged alive and after euthanasia for (oxy/deoxy)-hemoglobin content. A 0.4 mL volume of 1 μg/mL concentration of ICG was injected into the tail veins of two mice prior to imaging using the photoacoustic computed tomography (PCT) spectrometer (Optosonics, Inc., Indianapolis, IN 46202) scanner. Mouse images were acquired for wavelengths spanning 700-920 nm, after which the major organs were excised, and similarly imaged. A histological study was performed by sectioning the organ and optically imaging the fluorescence distribution. Results. Calibration of PCT-spectroscopy with different samples of oxygenated blood reproduced a hemoglobin dissociation curve consistent with empirical formula with an average error of 5.6%. In vivo PCT determination of SaO II levels within the tumor vascular was measurably tracked, and spatially correlated to the periphery of the tumor. Statistical and systematic errors associated with hypoxia were estimated to be 10 and 13%, respectively. Measured ICG concentrations determined by contrast-differential PCT images in excised organs (tumor, liver) were approximately 0.8 μg/mL, consistent with fluorescent histological results. Also, the difference in the ratio of ICG concentration in the gall bladder-to-vasculature between the mice was consistent with excretion times between the two mice. Conclusion. PCT spectroscopic imaging has shown to be a noninvasive modality capable of imaging intra-tumor heterogeneity of (oxy/deoxy)-hemoglobin and ICG in vivo, with an estimated error in SaO II at 17% and in ICG at 0.8 μg/mL in excised tissue. Ongoing development of spectroscopic analysis techniques, probe development, and calibration techniques are being developed to improve sensitivity to both exogenous molecular probes and (oxy/deoxy)-hemoglobin fraction.

Red cell substitutes.

PubMed

Winslow, Robert M

2007-01-01

Oxygen-carrying plasma expanders (blood substitutes) have been sought for over a century. Development of current products is a result of evolution in the understanding of proteins in general, of hemoglobin in particular, and of how cell-free hemoglobin interacts with the control of local blood flow to ensure adequate tissue oxygenation. Hemoglobin-based products are considered in four "generations" corresponding to major improvements. First-generation products consisted of hemoglobin, freed of red cell membranes (stroma-free hemoglobin [SFH]), which was renal toxic and vasoactive. Second-generation products were polymerized with aldehyde reagents to reduce or eliminate the renal toxicity, but the products were heterogeneous and still vasoactive. Third-generation products employed more specific intramolecular crosslinking to eliminate polymerization and promote homogeneity, but they also remained vasoactive. Fourth-generation products are based on a new understanding of the way in which microvascular blood flow is controlled and the influence of O(2) delivery to vascular walls. After more than a century of research, one of these new solutions should find use as an alternative to red cells for transfusion in certain clinical settings.

Optical fiber spectroscopy measures perfusion of the brain in a murine Alzheimer's disease model

NASA Astrophysics Data System (ADS)

Ahn, Hyung Jin; Strickland, Sidney; Krueger, James; Gareau, Daniel

2014-02-01

Optical fiber spectroscopy is a versatile tool for measuring diffuse reflectance and extracting absorption information that can noninvasively quantify the presence of chromophores such as oxyhemoglobin and deoxy-hemoglobin in tissues. Cerebrovascular abnormalities were widely recognized in Alzheimer's disease (AD) patients. We analyzed blood volume fraction and level of oxygenated hemoglobin in Tg6799 mice, which are transgenic mice expressing five different familial Alzheimer disease-associated mutations in the human amyloid precursor protein and presenilin-1 genes. Diffuse reflectance spectra were iteratively fit as weighted sums of oxy- and deoxy-hemoglobin. Our observations showed slightly hypoxic conditions and significantly increased blood volume in the Alzheimer's mice versus wild type. These results suggest that hyperperfusion of our AD mice may be a compensating mechanism for impaired cerebral vascular function and somehow relevant with early stage of AD patients. Ongoing work focuses on developing a cannula fixture that allows measurement in awake, behaving animals.

Transfection of the Human Heme Oxygenase Gene Into Rabbit Coronary Microvessel Endothelial Cells: Protective Effect Against Heme and Hemoglobin Toxicity

NASA Astrophysics Data System (ADS)

Abraham, N. G.; Lavrovsky, Y.; Schwartzman, M. L.; Stoltz, R. A.; Levere, R. D.; Gerritsen, M. E.

1995-07-01

Heme oxygenase (HO) is a stress protein and has been suggested to participate in defense mechanisms against agents that may induce oxidative injury such as metals, endotoxin, heme/hemoglobin, and various cytokines. Overexpression of HO in cells might therefore protect against oxidative stress produced by certain of these agents, specifically heme and hemoglobin, by catalyzing their degradation to bilirubin, which itself has antioxidant properties. We report here the successful in vitro transfection of rabbit coronary microvessel endothelial cells with a functioning gene encoding the human HO enzyme. A plasmid containing the cytomegalovirus promoter and the human HO cDNA complexed to cationic liposomes (Lipofectin) was used to transfect rabbit endothelial cells. Cells transfected with human HO exhibited an ≈3.0-fold increase in enzyme activity and expressed a severalfold induction of human HO mRNA as compared with endogenous rabbit HO mRNA. Transfected and nontransfected cells expressed factor VIII antigen and exhibited similar acetylated low-density lipoprotein uptake (two important features that characterize endothelial cells) with >85% of cells staining positive for each marker. Moreover, cells transfected with the human HO gene acquired substantial resistance to toxicity produced by exposure to recombinant hemoglobin and heme as compared with nontransfected cells. The protective effect of HO overexpression against heme/hemoglobin toxicity in endothelial cells shown in these studies provides direct evidence that the inductive response of human HO to such injurious stimuli represents an important tissue adaptive mechanism for moderating the severity of cell damage produced by these blood components.

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

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.

The aeromedical significance of sickle-cell trait : a review.

DOT National Transportation Integrated Search

1976-01-01

This report present some of the technical background necessary for understanding the aeromedical importance of sickle-cell disease and the sickle-trait carrier, whose erythrocytes contain mixtures of hemoglobin S and normal hemoglobin A. This carrier...

Genetics Home Reference: sickle cell disease

MedlinePlus

... of beta-globin; this abnormality is called beta thalassemia . In people with sickle cell disease , at least ... globin. If mutations that produce hemoglobin S and beta thalassemia occur together, individuals have hemoglobin S- beta thalassemia (HbSBetaThal) ...

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

PubMed Central

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

2010-01-01

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

The Hb E (HBB: c.79G>A), Mean Corpuscular Volume, Mean Corpuscular Hemoglobin Cutoff Points in Double Heterozygous Hb E/- -SEA α-Thalassemia-1 Carriers are Dependent on Hemoglobin Levels.

PubMed

Leckngam, Prapapun; Limweeraprajak, Ektong; Kiewkarnkha, Tiemjan; Tatu, Thanusak

2017-01-01

Identifying double heterozygosities in Hb E (HBB: c.79 G>A)/- - SEA (Southeast Asian) (α-thalassemia-1) (α-thal-1) in patients first diagnosed as carrying Hb E is important in thalassemia control. Low Hb E, mean corpuscular volume (MCV) and mean corpuscular hemoglobin (Hb) (MCH) levels have been observed in this double heterozygosity. However, the cutoff points of these parameters have never been systematically established. Here, we analyzed Hb E and red blood cell (RBC) parameters in 372 Hb E patients grouped by Hb levels, by the status of - - SEA and -α 3.7 (α-thal-2; rightward) deletions, to establish the cutoff points. Then, the established cutoff points were evaluated in 184 Hb E patients. It was found that the cutoff points of Hb E, MCV, MCH were significantly dependent on the Hb levels. In the group having Hb levels <10.0 g/dL, the cutoff points of Hb E, MCV and MCH were 21.2%, 64.9 fL and 21.0 pg, respectively, and were 25.6%, 72.8 fL and 23.9 pg, respectively, in the group having Hb levels 10.0-11.9 g/dL. Finally, in the group having Hb levels ≥12.0 g/dL, the cutoff points of Hb E, MCV and MCH were 27.1%, 76.7 fL and 25.3 pg, respectively. Thus, to screen for the double heterozygous Hb E/- - SEA anomaly in patients initially diagnosed as carrying Hb E, the Hb levels must be taken into account in choosing the suitable cutoff points of these three parameters.

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

[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.

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

Transient spontaneous engraftment of CD34 hematopoietic cord blood stem cells as seen in peripheral blood: treatment of leprosy patients with anemia by placental umbilical cord whole blood transfusion.

PubMed

Bhattacharya, N

2006-01-01

Cord blood, because of its rich mix of fetal and adult hemoglobin, high platelet and white blood cell (WBC) counts, and a plasma filled with cytokine and growth factors, as well as its hypoantigenic nature and altered metabolic profile, has all the potential of a real and safe alternative to adult blood transfusion. Our experience of 74 units (50 ml-146 ml mean, 86 ml +/- 7.6 ml SD, median 80 ml, mean packed cell volume 48 +/- 4.1 SD, mean percent hemoglobin concentration 16.2 g/dl +/- 1.8 g/dl of placental umbilical cord whole blood collection (from 1 April 1999) after lower uterine cesarean section (LUCS) from consenting mothers and transfusion of the same to 16 informed, consenting patients with percent plasma hemoglobin 8 g/dl or less, is presented here. After collection the blood was immediately preserved in the refrigerator and transfused within 72 hours of collection. Fifteen males and one female, aged 12-72 yrs (mean 48.4 yrs) participated: five cases were pausibacillary type (PB) and 11 cases were multibacillary type (MB). The clinical spectrum of the cases varied widely from the tuberculoid to the lepromatous type and one patient presented with gangrene of the leg preceding an auto amputation which was infested with maggots. Each case was approved by the institutional ethical committee and received two to eight units of freshly collected placental umbilical cord blood in one transfusion without encountering any clinical, immunological or non-immunological reaction. Seven days after completion of the placental umbilical cord blood transfusion, the peripheral blood hematopoietic stem cell (CD34) estimation revealed a rise from the pretransfusion base level (.09%), varying from 3.6% to 16.2%, in 75% of the cases, without provoking any clinical graft vs host reaction in any of the leprosy victims. This value returned to normal within three months in most cases.

Monomethylfumarate Induces γ-Globin Expression and Fetal Hemoglobin Production in Cultured Human Retinal Pigment Epithelial (RPE) and Erythroid Cells, and in Intact Retina

PubMed Central

Promsote, Wanwisa; Makala, Levi; Li, Biaoru; Smith, Sylvia B.; Singh, Nagendra; Ganapathy, Vadivel; Pace, Betty S.; Martin, Pamela M.

2014-01-01

Purpose. Sickle retinopathy (SR) is a major cause of vision loss in sickle cell disease (SCD). There are no strategies to prevent SR and treatments are extremely limited. The present study evaluated (1) the retinal pigment epithelial (RPE) cell as a hemoglobin producer and novel cellular target for fetal hemoglobin (HbF) induction, and (2) monomethylfumarate (MMF) as an HbF-inducing therapy and abrogator of oxidative stress and inflammation in SCD retina. Methods. Human globin gene expression was evaluated by RT–quantitative (q)PCR in the human RPE cell line ARPE-19 and in primary RPE cells isolated from Townes humanized SCD mice. γ-Globin promoter activity was monitored in KU812 stable dual luciferase reporter expressing cells treated with 0 to 1000 μM dimethylfumarate, MMF, or hydroxyurea (HU; positive control) by dual luciferase assay. Reverse transcriptase–qPCR, fluorescence-activated cell sorting (FACS), immunofluorescence, and Western blot techniques were used to evaluate γ-globin expression and HbF production in primary human erythroid progenitors, ARPE-19, and normal hemoglobin producing (HbAA) and homozygous βs mutation (HbSS) RPE that were treated similarly, and in MMF-injected (1000 μM) HbAA and HbSS retinas. Dihydroethidium labeling and nuclear factor (erythroid-derived 2)-like 2 (Nrf2), IL-1β, and VEGF expression were also analyzed. Results. Retinal pigment epithelial cells express globin genes and synthesize adult and fetal hemoglobin MMF stimulated γ-globin expression and HbF production in cultured RPE and erythroid cells, and in HbSS mouse retina where it also reduced oxidative stress and inflammation. Conclusions. The production of hemoglobin by RPE suggests the potential involvement of this cell type in the etiology of SR. Monomethylfumarate influences multiple parameters consistent with improved retinal health in SCD and may therefore be of therapeutic potential in SR treatment. PMID:24825111

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

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.

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.

A Theoretical Study of some Rheological Properties of the Aggregation of the Molecules Deoxy- Hemoglobin S

NASA Astrophysics Data System (ADS)

Mensah, Francis; Grant, Julius; Thorpe, Arthur

2010-02-01

Sickle cell disease is a serious public health problem that affects many people worldwide. In this paper, the Langevin equation is used for hemoglobin's aggregation in sickle cell anemia. Several parameters are explored such as the time-dependent deformation of the aggregates whose plot gives a sigmoid, the time-dependent expressions obtained for the coefficient of viscosity and the elastic modulus which characterize the aggregation of the sickle hemoglobin. Other properties such as the viscoelastic and the elasto-thixotropic properties of the sickle hemoglobin polymer are also described. An attempt is made to approach the polymerization process in terms of a dynamical system. )

Disease resistance and health parameters of growth-hormone transgenic and wild-type coho salmon, Oncorhynchus kisutch.

PubMed

Kim, Jin-Hyoung; Balfry, Shannon; Devlin, Robert H

2013-06-01

To extend previous findings regarding fish health and disease susceptibility of growth-enhanced fish, hematological and immunological parameters have been compared between growth hormone (GH) transgenic and wild-type non-transgenic coho salmon (Oncorhynchus kisutch). Compared to non-transgenic coho salmon, transgenic fish had significantly higher hematocrit (Hct), hemoglobin (Hb), mean cellular hemoglobin (MCH), mean cellular volume (MCV), and erythrocyte numbers, and lower white cell numbers. In addition, resistance to the bacterial pathogen Aeromonas salmonicida (causal agent of furunculosis) has been assessed between the strains. Higher susceptibility of transgenic fish to this disease challenge was observed in two separate year classes of fish. The present findings provide fundamental knowledge of the disease resistance on GH enhanced transgenic coho salmon, which is of importance for assessing the fitness of transgenic strains for environmental risk assessments, and for improving our understanding effects of growth modification on basic immune functions. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

Differentiating between dengue fever and malaria using hematological parameters in endemic areas of Thailand.

PubMed

Kotepui, Manas; PhunPhuech, Bhukdee; Phiwklam, Nuoil; Uthaisar, Kwuntida

2017-03-02

Dengue fever (DF) and malaria are the two major public health concerns in tropical countries such as Thailand. Early differentiation between dengue and malaria could help clinicians to identify patients who should be closely monitored for signs of dengue hemorrhagic fever or severe malaria. This study aims to build knowledge on diagnostic markers that are used to discriminate between the infections, which frequently occur in malaria-endemic areas, such as the ones in Thailand. A retrospective study was conducted in Phop Phra Hospital, a hospital located in the Thailand-Burma border area, a malaria-endemic area, between 2013 and 2015. In brief, data on 336 patients infected with malaria were compared to data on 347 patients infected with DF. White blood cells, neutrophil, monocyte, eosinophil, neutrophil-lymphocyte ratio, and monocyte-lymphocyte ratio were significantly lower in patients with DF compared to patients with malaria (P < 0.0001). In contrast, red blood cells, hemoglobin, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration were significantly higher in patients with DF as compared to patients with malaria (P < 0.0001). A decision tree model revealed that using neutrophils, lymphocyte, MCHC, and gender was guided to discriminate between dengue and malaria infection. This study concluded that several hematological parameters were different for diagnosing DF and malaria. A decision tree model revealed that using neutrophils, lymphocyte, MCHC, and gender was guided to discriminate patients with dengue and malaria infection. In addition, using these markers will thus lead to early detection, diagnosis, and prompt treatment of these tropical diseases.

Simultaneous, noninvasive, in vivo, continuous monitoring of hematocrit, vascular volume, hemoglobin oxygen saturation, pulse rate and breathing rate in humans and other animal models using a single light source

NASA Astrophysics Data System (ADS)

Dent, Paul; Tun, Sai Han; Fillioe, Seth; Deng, Bin; Satalin, Josh; Nieman, Gary; Wilcox, Kailyn; Searles, Quinn; Narsipur, Sri; Peterson, Charles M.; Goodisman, Jerry; Mostrom, James; Steinmann, Richard; Chaiken, J.

2018-02-01

We previously reported a new algorithm "PV[O]H" for continuous, noninvasive, in vivo monitoring of hematocrit changes in blood and have since shown its utility for monitoring in humans during 1) hemodialysis, 2) orthostatic perturbations and 3) during blood loss and fluid replacement in a rat model. We now show that the algorithm is sensitive to changes in hemoglobin oxygen saturation. We document the phenomenology of the effect and explain the effect using new results obtained from humans and rat models. The oxygen sensitivity derives from the differential absorption of autofluorescence originating in the static tissues by oxy and deoxy hemoglobin. Using this approach we show how to perform simultaneous, noninvasive, in vivo, continuous monitoring of hematocrit, vascular volume, hemoglobin oxygen saturation, pulse rate and breathing rate in mammals using a single light source. We suspect that monitoring of changes in this suite of vital signs can be provided with improved time response, sensitivity and precision compared to existing methodologies. Initial results also offer a more detailed glimpse into the systemic oxygen transport in the circulatory system of humans.

[Targeted newborn screening for sickle-cell anemia: Sickling test (Emmel test) boundaries in the prenatal assessment in West African area].

PubMed

Diallo, D A; Guindo, A; Touré, B A; Sarro, Y S; Sima, M; Tessougué, O; Baraika, M A; Guindo, P; Traoré, M; Diallo, M; Dorie, A

2018-05-01

Newborn screening for sickle cell anemia is necessary in Africa where the disease is more frequent. Hemoglobin electrophoresis is used for screening, but is limited by a high cost and difficult access. Sickling test (Emmel test), which is more affordable and technically more accessible, is often requested for prenatal assessment of pregnant women in West African areas to reserve screening for newborns from mothers in whom the positive sickling test attests the presence of hemoglobin S. This study aims to evaluate the number of undetected sickle cell anemia newborns by a screening policy targeting only newborns from mothers in whom a sickling test would have been positive. From 2010 to 2012, in Bamako, Mali, West Africa, 2489 newborns were routinely screened for sickle cell anemia at the umbilical cord or heel by isoelectrofocusing and, if necessary, by high-performance liquid chromatography. These newborns were born from 2420 mothers whose hemoglobin was studied by isoelectrofocusing. The data was recorded and processed using Excel software version 14.0.0. We calculated the frequency of the sickle cell gene in mothers and newborns as well as the number of SCA newborns from heterozygous or C homozygous mothers. Of the 2489 newborns, 16 had sickle cell anemia (6 SS and 10 SC); 198 had the sickle cell trait; 139 were AC and 1 was CC. Of the 10 newborns with SC profile, 3 were born from mothers not carrying the S gene but the C gene of hemoglobin and in which an Emmel test would have been negative. Targeted newborn screening, based on the results of sickling test in pregnant women, would misdiagnose more than one of six sickle cell anemia newborns who would not benefit from early care. Cost-effectiveness studies of routine newborn screening for sickle cell anemia should lead to a better screening strategy in contexts where hemoglobin S and other hemoglobin defect genes coexist. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

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.

Protein quality, hematological properties and nutritional status of albino rats fed complementary foods with fermented popcorn, African locust bean, and bambara groundnut flour blends

PubMed Central

Keshinro, Oluremi Olufunke

2012-01-01

The objective of this study was to determine protein quality and hematological properties of infant diets formulated from local food materials. The food materials were obtained locally, fermented, and milled into flour. The flours were mixed as 70% popcorn and 30% African locust bean (FPA), 70% popcorn and 30% bambara groundnut (FPB), and 70% popcorn, 20% bambara groundnut, and 10% African locust bean (FPAB). Proximate analysis, protein quality, hematological properties, and anthropometric measurements of the animals fed with the formulations were investigated. The protein contents of the formulated diets were significantly higher than that of Cerelac (a commercial preparation) (15.75 ± 0.01 g/100 g) and ogi (traditional complementary food) (6.52 ± 0.31 g/100 g). The energy value of FPAB (464.94 ± 1.22 kcal) was higher than those of FPA (441.41 ± 3.05 kcal) and FPB (441.48 ± 3.05 kcal). The biological value (BV) of FPAB (60.20%) was the highest followed by FPB (44.24%) and FPA (41.15%); however, BV of the diets was higher than that of ogi (10.03%) but lower than that of Cerelac (70.43%). Net protein utilization (NPU) of the formulations was 41.16-60.20%, whereas true protein digestibility was 41.05-60.05%. Metabolizable energy (232.98 kcal) and digestible energy (83.69 kcal) of FPAB were the highest, whereas that of FPA had the lowest values. The protein digestibility values corrected for amino acid score of the diets (0.22-0.44) were lower than that of Cerelac (0.52), but higher than that of ogi (0.21). The growth patterns and hematological properties (packed cell volume, red blood cells, hemoglobin, mean corpuscular hemoglobin concentration, mean corpuscular hemoglobin, and mean corpuscular volume) of the formulated diets were higher than those of ogi, but lower than those of Cerelac. In conclusion, we established that the FPAB food sample was rated best in terms of protein quality over the other formulated diets. Therefore, a FPAB blend may be used as a substitute for ogi. PMID:23198016

Protein quality, hematological properties and nutritional status of albino rats fed complementary foods with fermented popcorn, African locust bean, and bambara groundnut flour blends.

PubMed

Ijarotimi, Oluwole Steve; Keshinro, Oluremi Olufunke

2012-10-01

The objective of this study was to determine protein quality and hematological properties of infant diets formulated from local food materials. The food materials were obtained locally, fermented, and milled into flour. The flours were mixed as 70% popcorn and 30% African locust bean (FPA), 70% popcorn and 30% bambara groundnut (FPB), and 70% popcorn, 20% bambara groundnut, and 10% African locust bean (FPAB). Proximate analysis, protein quality, hematological properties, and anthropometric measurements of the animals fed with the formulations were investigated. The protein contents of the formulated diets were significantly higher than that of Cerelac (a commercial preparation) (15.75 ± 0.01 g/100 g) and ogi (traditional complementary food) (6.52 ± 0.31 g/100 g). The energy value of FPAB (464.94 ± 1.22 kcal) was higher than those of FPA (441.41 ± 3.05 kcal) and FPB (441.48 ± 3.05 kcal). The biological value (BV) of FPAB (60.20%) was the highest followed by FPB (44.24%) and FPA (41.15%); however, BV of the diets was higher than that of ogi (10.03%) but lower than that of Cerelac (70.43%). Net protein utilization (NPU) of the formulations was 41.16-60.20%, whereas true protein digestibility was 41.05-60.05%. Metabolizable energy (232.98 kcal) and digestible energy (83.69 kcal) of FPAB were the highest, whereas that of FPA had the lowest values. The protein digestibility values corrected for amino acid score of the diets (0.22-0.44) were lower than that of Cerelac (0.52), but higher than that of ogi (0.21). The growth patterns and hematological properties (packed cell volume, red blood cells, hemoglobin, mean corpuscular hemoglobin concentration, mean corpuscular hemoglobin, and mean corpuscular volume) of the formulated diets were higher than those of ogi, but lower than those of Cerelac. In conclusion, we established that the FPAB food sample was rated best in terms of protein quality over the other formulated diets. Therefore, a FPAB blend may be used as a substitute for ogi.

Transcriptional Mechanisms Underlying Hemoglobin Synthesis

PubMed Central

Katsumura, Koichi R.; DeVilbiss, Andrew W.; Pope, Nathaniel J.; Johnson, Kirby D.; Bresnick, Emery H.

2013-01-01

The physiological switch in expression of the embryonic, fetal, and adult β-like globin genes has garnered enormous attention from investigators interested in transcriptional mechanisms and the molecular basis of hemoglobinopathies. These efforts have led to the discovery of cell type-specific transcription factors, unprecedented mechanisms of transcriptional coregulator function, genome biology principles, unique contributions of nuclear organization to transcription and cell function, and promising therapeutic targets. Given the vast literature accrued on this topic, this article will focus on the master regulator of erythroid cell development and function GATA-1, its associated proteins, and its frontline role in controlling hemoglobin synthesis. GATA-1 is a crucial regulator of genes encoding hemoglobin subunits and heme biosynthetic enzymes. GATA-1-dependent mechanisms constitute an essential regulatory core that nucleates additional mechanisms to achieve the physiological control of hemoglobin synthesis. PMID:23838521

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

PubMed Central

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

2014-01-01

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

Sickle Trait in African-American Hemodialysis Patients and Higher Erythropoiesis-Stimulating Agent Dose

PubMed Central

Lacson, Eduardo K.; Kshirsagar, Abhijit V.; Key, Nigel S.; Hogan, Susan L.; Hakim, Raymond M.; Mooney, Ann; Jani, Chinu M.; Johnson, Curtis; Hu, Yichun; Falk, Ronald J.; Lazarus, J. Michael

2014-01-01

African Americans require higher doses of erythropoiesis-stimulating agents (ESAs) during dialysis to manage anemia, but the influence of sickle cell trait and other hemoglobinopathy traits on anemia in dialysis patients has not been adequately evaluated. We performed a cross-sectional study of a large cohort of adult African-American hemodialysis patients in the United States to determine the prevalence of hemoglobinopathy traits and quantify their influence on ESA dosing. Laboratory and clinical data were obtained over 6 months in 2011. Among 5319 African-American patients, 542 (10.2%) patients had sickle cell trait, and 129 (2.4%) patients had hemoglobin C trait; no other hemoglobinopathy traits were present. Sickle cell trait was more common in this cohort than the general African-American population (10.2% versus 6.5%–8.7%, respectively, P<0.05). Among 5002 patients (10.3% sickle cell trait and 2.4% hemoglobin C trait) receiving ESAs, demographic and clinical variables were similar across groups, with achieved hemoglobin levels being nearly identical. Patients with hemoglobinopathy traits received higher median doses of ESA than patients with normal hemoglobin (4737.4 versus 4364.1 units/treatment, respectively, P=0.02). In multivariable analyses, hemoglobinopathy traits associated with 13.2% more ESA per treatment (P=0.001). Within subgroups, sickle cell trait patients received 13.2% (P=0.003) higher dose and hemoglobin C trait patients exhibited a similar difference (12.9%, P=0.12). Sensitivity analyses using weight-based dosing definitions and separate logistic regression models showed comparable associations. Our findings suggest that the presence of sickle cell trait and hemoglobin C trait may explain, at least in part, prior observations of greater ESA doses administered to African-American dialysis patients relative to Caucasian patients. PMID:24459231

Sickle Cell Anemia and Its Phenotypes.

PubMed

Williams, Thomas N; Thein, Swee Lay

2018-04-11

In the 100 years since sickle cell anemia (SCA) was first described in the medical literature, studies of its molecular and pathophysiological basis have been at the vanguard of scientific discovery. By contrast, the translation of such knowledge into treatments that improve the lives of those affected has been much too slow. Recent years, however, have seen major advances on several fronts. A more detailed understanding of the switch from fetal to adult hemoglobin and the identification of regulators such as BCL11A provide hope that these findings will be translated into genomic-based approaches to the therapeutic reactivation of hemoglobin F production in patients with SCA. Meanwhile, an unprecedented number of new drugs aimed at both the treatment and prevention of end-organ damage are now in the pipeline, outcomes from potentially curative treatments such as allogeneic hematopoietic stem cell transplantation are improving, and great strides are being made in gene therapy, where methods employing both antisickling β-globin lentiviral vectors and gene editing are now entering clinical trials. Encouragingly, after a century of neglect, the profile of the vast majority of those with SCA in Africa and India is also finally improving. Expected final online publication date for the Annual Review of Genomics and Human Genetics Volume 19 is August 31, 2018. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

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…

Bivariate and multivariate analyses of the influence of blood variables of patients submitted to Roux-en-Y gastric bypass on the stability of erythrocyte membrane against the chaotropic action of ethanol.

PubMed

de Arvelos, Leticia Ramos; Rocha, Vanessa Custódio Afonso; Felix, Gabriela Pereira; da Cunha, Cleine Chagas; Bernardino Neto, Morun; da Silva Garrote Filho, Mario; de Fátima Pinheiro, Conceição; Resende, Elmiro Santos; Penha-Silva, Nilson

2013-03-01

The stability of the erythrocyte membrane, which is essential for the maintenance of cell functions, occurs in a critical region of fluidity, which depends largely on its composition and the composition and characteristics of the medium. As the composition of the erythrocyte membrane is influenced by several blood variables, the stability of the erythrocyte membrane must have relations with them. The present study aimed to evaluate, by bivariate and multivariate statistical analyses, the correlations and causal relationships between hematologic and biochemical variables and the stability of the erythrocyte membrane against the chaotropic action of ethanol. The validity of this type of analysis depends on the homogeneity of the population and on the variability of the studied parameters, conditions that can be filled by patients who undergo bariatric surgery by the technique of Roux-en-Y gastric bypass since they will suffer feeding restrictions that have great impact on their blood composition. Pathway analysis revealed that an increase in hemoglobin leads to decreased stability of the cell, probably through a process mediated by an increase in mean corpuscular volume. Furthermore, an increase in the mean corpuscular hemoglobin (MCH) leads to an increase in erythrocyte membrane stability, probably because higher values of MCH are associated with smaller quantities of red blood cells and a larger contact area between the cell membrane and ethanol present in the medium.

Improved hydroxyurea effect with the use of text messaging in children with sickle cell anemia.

PubMed

Estepp, Jeremie H; Winter, Bryan; Johnson, Margery; Smeltzer, Matthew P; Howard, Scott C; Hankins, Jane S

2014-11-01

In children with sickle cell anemia (SCA), hydroxyurea reduces morbidity, but adherence is frequently suboptimal. Because most families of children with SCA have access to cellular telephone services, we assessed the impact of text messaged reminders as a tool to improve adherence to hydroxyurea. All patients <19 years of age with HbSS or HbSβ(0) thalassemia who were treated with hydroxyurea at a maximal tolerated dosage (MTD) at St. Jude Children's Research Hospital Comprehensive Pediatric Sickle Cell Program and who received automated text message reminders (SIMON®) were retrospectively identified. Laboratory parameters, hospitalizations, and medication possession ratios (MPR) prior to and after initiation of SIMON® were compared to assess the impact of SIMON®. Of the 97.3% of families with access to a cell phone, 91% elected to receive text message reminders. Among 55 children receiving hydroxyurea at MTD, laboratory parameters reflected waning medication compliance during the 12 months prior to SIMON®. Following initiation of SIMON®, children had higher mean corpuscular volumes, hemoglobin levels and fetal hemoglobin percentages and lower absolute reticulocyte counts and bilirubin levels, suggesting improved medication adherence. Hospitalizations were uncommon before and after SIMON®, and medication possession ratios (MPRs) were high before and after SIMON®, neither was significantly changed. SIMON® was feasible and improved hematologic parameters in children with SCA receiving hydroxyurea at a MTD. Future work will include extension of this technology to children with other chronic medical conditions who require daily use of medication. © 2014 Wiley Periodicals, Inc.

A microfluidic device integrating dual CMOS polysilicon nanowire sensors for on-chip whole blood processing and simultaneous detection of multiple analytes.

PubMed

Kuan, Da-Han; Wang, I-Shun; Lin, Jiun-Rue; Yang, Chao-Han; Huang, Chi-Hsien; Lin, Yen-Hung; Lin, Chih-Ting; Huang, Nien-Tsu

2016-08-02

The hemoglobin-A1c test, measuring the ratio of glycated hemoglobin (HbA1c) to hemoglobin (Hb) levels, has been a standard assay in diabetes diagnosis that removes the day-to-day glucose level variation. Currently, the HbA1c test is restricted to hospitals and central laboratories due to the laborious, time-consuming whole blood processing and bulky instruments. In this paper, we have developed a microfluidic device integrating dual CMOS polysilicon nanowire sensors (MINS) for on-chip whole blood processing and simultaneous detection of multiple analytes. The micromachined polymethylmethacrylate (PMMA) microfluidic device consisted of a serpentine microchannel with multiple dam structures designed for non-lysed cells or debris trapping, uniform plasma/buffer mixing and dilution. The CMOS-fabricated polysilicon nanowire sensors integrated with the microfluidic device were designed for the simultaneous, label-free electrical detection of multiple analytes. Our study first measured the Hb and HbA1c levels in 11 clinical samples via these nanowire sensors. The results were compared with those of standard Hb and HbA1c measurement methods (Hb: the sodium lauryl sulfate hemoglobin detection method; HbA1c: cation-exchange high-performance liquid chromatography) and showed comparable outcomes. Finally, we successfully demonstrated the efficacy of the MINS device's on-chip whole blood processing followed by simultaneous Hb and HbA1c measurement in a clinical sample. Compared to current Hb and HbA1c sensing instruments, the MINS platform is compact and can simultaneously detect two analytes with only 5 μL of whole blood, which corresponds to a 300-fold blood volume reduction. The total assay time, including the in situ sample processing and analyte detection, was just 30 minutes. Based on its on-chip whole blood processing and simultaneous multiple analyte detection functionalities with a lower sample volume requirement and shorter process time, the MINS device can be effectively applied to real-time diabetes diagnostics and monitoring in point-of-care settings.

Toxicity of dietary lead in young cockerels

USGS Publications Warehouse

Franson, J. Christian; Custer, Thomas W.

1982-01-01

Day-old cockerels received 1850 ppm dietary lead for 4 wks. Blood delta-aminolevulinic acid dehydratase (ALAD) activity was reduced to 1.6% of control activity by the end of the study. Hemoglobin concentration (Hb) in lead-exposed cockerels was significantly less than that of controls at 7, 14, and 28 days, and packed cell volume (PCV) was significantly reduced at 14 days. Blood lead residues reached 832 ug/dl in exposed cockerels; kidney residues were about three times liver residues. At the termination of the study mean body weight of lead-exposed birds was 47% of controls.

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.

The Effects of Acute High-Intensity Interval Training on Hematological Parameters in Sedentary Subjects.

PubMed

Belviranli, Muaz; Okudan, Nilsel; Kabak, Banu

2017-07-19

The objective of the study was to determine the effects of acute high-intensity interval training (HIIT) on hematological parameters in sedentary men. Ten healthy, non-smoker, and sedentary men aged between 18 and 24 years participated in the study. All subjects performed four Wingate tests with 4 min intervals between the tests. Blood samples were collected at pre-exercise, immediately after, 3 and 6 h after the fourth Wingate test. Hematological parameters were analyzed in these samples. The results showed that hematocrit percentage, hemoglobin values, red cell count, mean cell volume, platelet count, total white cell count, and counts of the white cell subgroups increased immediately after the acute HIIT and their values began to return to resting levels 3 h after exercise, and completely returned to resting levels 6 h after exercise. In conclusion, acute HIIT causes an inflammatory response in blood.

[Specific features of blood cell composition and structure in fishes from the pelagial and coastal zones of Lake Baikal].

PubMed

Iakhnenko, V M; Klimenkov, I V

2009-01-01

Differences in the proportions and ultrastructure of peripheral blood cells between the Baikal cisco and roach have been revealed. Both species contain all main cell types involved in the immune response in higher vertebrates. However, cells mediating the innate immune response are represented in the Baikal cisco only by monocytes and pseudogranulocytes, whereas the blood of roach additionally contains true granulocytes. Significantly greater numbers of leukocytes and thrombocytes per unit volume in the roach are evidence for mobilization of the immune system in this species. The peripheral blood of both species contains lymphocytes, which are responsible for adaptive immunity. The content of hemoglobin in erythrocytes is lower in the roach than in the Baikal cisco. The state of blood in the two species may be considered adapted to typical conditions in their habitats.

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.

Toxic Hazards Research Unit. Annual Technical Report. 1978

DTIC Science & Technology

1978-08-01

determinations made for the following battery of clinical tests: HCT Bilirubin RBC Glucose WBC Triglycerides HGB Iron Alkaline Sedimentation Phosphatase Rate ...Count WBC Hematocrit HCT Hemoglobin HGB Sedimentation Rate SEDI Reticulocytes RETIC MCORP Mean Corpuscular Volume MCV Mean Corpuscular Hemoglobin MCH...Contract F33615-76-C-5005 9. PERFORMING ORGANIZATION NAME AND ADDRESS 10. PPOGPAM ELEMENT, PROJECT , TASK University of California, Irvine APEA A WORK UNIT

Proceedings of the 2010 AFMS Medical Research Symposium. Volume 5. Nursing Track: Abstracts and Presentations

DTIC Science & Technology

2011-03-15

management, toxicology/health risks (e.g., particulates nanomaterials, radiation, etc.), monitoring disease trends , other areas of preventive medicine...will include hematocrit, hemoglobin, mean corpuscle volume, iron, total iron binding capacity, Ferritin , and soluble transferring receptor. The

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.

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

Nanobiotechnology for hemoglobin-based blood substitutes.

PubMed

Chang, T M S

2009-04-01

Nanobiotechnology is the assembling of biological molecules into nanodimension complexes. This has been used for the preparation of polyhemoglobin formed by the assembling of hemoglobin molecules into a soluble nanodimension complex. New generations of this approach include the nanobiotechnological assembly of hemoglobin, catalase, and superoxide dismutase into a soluble nanodimension complex. This acts as an oxygen carrier and an antioxidant for those conditions with potential for ischemiareperfusion injuries. Another recent novel approach is the assembling of hemoglobin and fibrinogen into a soluble nanodimension polyhemoglobin-fibrinogen complex that acts as an oxygen carrier with platelet-like activity. This is potentially useful in cases of extensive blood loss requiring massive replacement using blood substitutes, resulting in the need for the replacement of platelets and clotting factors. A further step is the preparation of nanodimension artificial red blood cells that contain hemoglobin and all the enzymes present in red blood cells.

Residual blood processing by centrifugation, cell salvage or ultrafiltration in cardiac surgery: effects on clinical hemostatic and ex-vivo rheological parameters.

PubMed

Vonk, Alexander B; Muntajit, Warayouth; Bhagirath, Pranav; van Barneveld, Laurentius J; Romijn, Johannes W; de Vroege, Roel; Boer, Christa

2012-10-01

The study compared the effects of three blood concentration techniques after cardiopulmonary bypass on clinical hemostatic and ex-vivo rheological parameters. Residual blood of patients undergoing elective cardiac surgery was processed by centrifugation, cell salvage or ultrafiltration, and retransfused (n = 17 per group). Study parameters included blood loss, (free) hemoglobin, hematocrit, fibrinogen and erythrocyte aggregation, deformability and 2,3-diphosphoglycerate content. Patient characteristics were similar between groups. Ultrafiltration was associated with the highest weight of the transfusion bag [649 ± 261 vs. 320 ± 134 g (centrifugation) and 391 ± 158 g (cell salvage); P < 0.01]. Cell salvage resulted in the lowest hemolysis levels in the transfusion bag. Retransfusion of cell saver blood induced the largest gain in postoperative patient hemoglobin levels when compared to centrifugation and ultrafiltration, and was associated with the largest increase in 2,3-diphosphoglycerate when compared to ultrafiltration (Δ2,3-diphosphoglycerate 1.34 ± 1.92 vs. -0.77 ± 1.56 mmol/l; P = 0.03). Cell salvage is superior with respect to postoperative hemoglobin gain and washout of free hemoglobin when compared to centrifugation or ultrafiltration.

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.

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

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.

Imaging hypoxia using 3D photoacoustic spectroscopy

NASA Astrophysics Data System (ADS)

Stantz, Keith M.

2010-02-01

Purpose: The objective is to develop a multivariate in vivo hemodynamic model of tissue oxygenation (MiHMO2) based on 3D photoacoustic spectroscopy. Introduction: Low oxygen levels, or hypoxia, deprives cancer cells of oxygen and confers resistance to irradiation, some chemotherapeutic drugs, and oxygen-dependent therapies (phototherapy) leading to treatment failure and poor disease-free and overall survival. For example, clinical studies of patients with breast carcinomas, cervical cancer, and head and neck carcinomas (HNC) are more likely to suffer local reoccurrence and metastasis if their tumors are hypoxic. A novel method to non invasively measure tumor hypoxia, identify its type, and monitor its heterogeneity is devised by measuring tumor hemodynamics, MiHMO2. Material and Methods: Simulations are performed to compare tumor pO2 levels and hypoxia based on physiology - perfusion, fractional plasma volume, fractional cellular volume - and its hemoglobin status - oxygen saturation and hemoglobin concentration - based on in vivo measurements of breast, prostate, and ovarian tumors. Simulations of MiHMO2 are performed to assess the influence of scanner resolutions and different mathematic models of oxygen delivery. Results: Sensitivity of pO2 and hypoxic fraction to photoacoustic scanner resolution and dependencies on model complexity will be presented using hemodynamic parameters for different tumors. Conclusions: Photoacoustic CT spectroscopy provides a unique ability to monitor hemodynamic and cellular physiology in tissue, which can be used to longitudinally monitor tumor oxygenation and its response to anti-angiogenic therapies.

The influence of hydroxyurea on oxidative stress in sickle cell anemia

PubMed Central

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

2012-01-01

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

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.

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.

Live high-train low for 24 days increases hemoglobin mass and red cell volume in elite endurance athletes.

PubMed

Wehrlin, Jon Peter; Zuest, Peter; Hallén, Jostein; Marti, Bernard

2006-06-01

The effect of live high-train low on hemoglobin mass (Hbmass) and red cell volume (RCV) in elite endurance athletes is still controversial. We expected that Hb(mass) and RCV would increase, when using a presumably adequate hypoxic dose. An altitude group (AG) of 10 Swiss national team orienteers (5 men and 5 women) lived at 2,500 m (18 h per day) and trained at 1,800 and 1,000 m above sea level for 24 days. Before and after altitude, Hbmass, RCV (carbon monoxide rebreathing method), blood, iron, and performance parameters were determined. Seven Swiss national team cross-country skiers (3 men and 4 women) served as "sea level" (500-1,600 m) control group (CG) for the changes in Hbmass and RCV. The AG increased Hbmass (805+/-209 vs. 848+/-225 g; P<0.01) and RCV (2,353+/-611 vs. 2,470+/-653 ml; P<0.01), whereas there was no change for the CG (Hbmass: 849+/-197 vs. 858+/-205 g; RCV: 2,373+/-536 vs. 2,387+/-551 ml). Serum erythropoietin (P<0.001), reticulocytes (P<0.001), transferrin (P<0.001), soluble transferrin receptor (P<0.05), and hematocrit (P<0.01) increased, whereas ferritin (P<0.05) decreased in the AG. These changes were associated with an increased maximal oxygen uptake (3,515+/-837 vs. 3,660+/-770 ml/min; P<0.05) and improved 5,000-m running times (1,098+/-104 vs. 1,080+/-98 s; P<0.01) from pre- to postaltitude. Living at 2,500 m and training at lower altitudes for 24 days increases Hbmass and RCV. These changes may contribute to enhance performance of elite endurance athletes.

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.

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

PubMed

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

2014-01-01

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

Placental umbilical cord whole blood transfusion to combat anemia in the background of tuberculosis and emaciation and its potential role as an immuno-adjuvant therapy for the under-resourced people of the world.

PubMed

Bhattacharya, N

2006-01-01

Tuberculosis causes approximately 1.5 billion latent infections, 8 million new clinical cases, and 3 million deaths annually, making it the most prevalent infectious disease in the world. Anemia and malnutrition are essential comorbidities with tuberculosis. Cord blood, because of its rich mix of fetal and adult hemoglobin, high platelet and WBC counts, and a plasma filled with cytokine and growth factors, as well as its hypo-antigenic nature and altered metabolic profile, has all the potential of a real and safe alternative to adult blood transfusion. We transfused 106 units (48 ml-148 ml mean 81 ml +/- 6.6 ml SD, median 82 ml, mean packed cell volume 49.4 +/- 3.1 SD, mean percent hemoglobin concentration 16.3 g/dl +/- 1.7 g/dl SD) of placental umbilical cord whole blood (from 1 April 1999 to 1st 2005) after lower uterine cesarean section from consenting mothers to 21 informed consenting patients with tuberculosis who had percent plasma hemoglobin of 8 g/dl or less. After collection, the blood was immediately transfused following the standard adult blood transfusion protocol. Each case was passed through the institutional ethical committee. The patients received 2-21 units of freshly collected placental umbilical cord blood without encountering any clinical, immunological or non-immunological reactions. Three days after completion of the placental umbilical cord blood transfusion, the peripheral blood hematopoietic stem cell (CD34) estimation revealed a rise from the pretransfusion base level (.09%), varying from 2.99% to 33%, which returned to base level in 66.66% at the three-month CD34 re-estimation, without provoking any clinical graft vs host reaction in any of the patients.

Hemopoiesis in the pig-tailed monkey Macaca nemestrina during chronic altitude exposure.

NASA Technical Reports Server (NTRS)

Buderer, M. C.; Pace, N.

1972-01-01

Study of monkeys for 180 days at 3800 m altitude to examine their hemopoietic response. Plasma volume was found to be reduced while red cell volume increased steadily for four to five months. Reduction in mean corpuscular hemoglobin content was observed from day 30 to day 120 at altitude. Total plasma protein concentration was unchanged at altitude, but marked reduction in the albumin/globulin ratio occurred. Total circulating plasma protein and albumin were reduced in amount, whereas nonalbumin protein was unchanged. These results imply loss of albumin coupled with a corresponding loss of water from the blood and maintenance of normal plasma osmotic pressure. The body/venous hematocrit ratio was found to be reduced at altitude, possibly as a consequence of the expanded capillary volume of the body. The hemopoietic responses of the pig-tailed monkey at altitude require at least several months for completion, and closely resemble those seen in man; thus, the monkey can serve well for long-term studies of high-altitude acclimatization.

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 ...

Stimulation of eryptosis by aluminium ions

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

Niemoeller, Olivier M.; Kiedaisch, Valentin; Dreischer, Peter

2006-12-01

Aluminium salts are utilized to impede intestinal phosphate absorption in chronic renal failure. Toxic side effects include anemia, which could result from impaired formation or accelerated clearance of circulating erythrocytes. Erythrocytes may be cleared secondary to suicidal erythrocyte death or eryptosis, which is characterized by cell shrinkage and exposure of phosphatidylserine (PS) at the erythrocyte surface. As macrophages are equipped with PS receptors, they bind, engulf and degrade PS-exposing cells. The present experiments have been performed to explore whether Al{sup 3+} ions trigger eryptosis. The PS exposure was estimated from annexin binding and cell volume from forward scatter in FACSmore » analysis. Exposure to Al{sup 3+} ions ({>=} 10 {mu}M Al{sup 3+} for 24 h) indeed significantly increased annexin binding, an effect paralleled by decrease of forward scatter at higher concentrations ({>=} 30 {mu}M Al{sup 3+}). According to Fluo3 fluorescence Al{sup 3+} ions ({>=} 30 {mu}M for 3 h) increased cytosolic Ca{sup 2+} activity. Al{sup 3+} ions ({>=} 10 {mu}M for 24 h) further decreased cytosolic ATP concentrations. Energy depletion by removal of glucose similarly triggered annexin binding, an effect not further enhanced by Al{sup 3+} ions. The eryptosis was paralleled by release of hemoglobin, pointing to loss of cell membrane integrity. In conclusion, Al{sup 3+} ions decrease cytosolic ATP leading to activation of Ca{sup 2+}-permeable cation channels, Ca{sup 2+} entry, stimulation of cell membrane scrambling and cell shrinkage. Moreover, Al{sup 3+} ions lead to loss of cellular hemoglobin, a feature of hemolysis. Both effects are expected to decrease the life span of circulating erythrocytes and presumably contribute to the development of anemia during Al{sup 3+} intoxication.« less

Multispectral and phase-contrast diffuse optical tomography of breast cancer during neoadjuvant chemotherapy: a case study

NASA Astrophysics Data System (ADS)

Liang, Xiaoping; Zhang, Qizhi; Staal, Stephen; Grobmyer, Stephen; Jiang, Huabei

2009-02-01

Multispectral and phase-contrast diffuse optical tomography are used to track treatment progress in a patient with locally advanced invasive carcinoma of the breast cancer during neoadjuvant chemotherapy. Two types of chemotherapy treatment including four cycles of Adriamycin/Cytoxin (AC cycles) and twelve cycles of Taxol/Herceptin (TH cycles) were applied to patient. A total of eight optical exams were performed before and within the chemotherapy. Images of tissue refractive index, and absorption and scattering coefficients, as well as oxy-hemoglobin and deoxy-hemoglobin concentrations along with scattering particle volume fraction and mean diameter of cellular components were all obtained. The tumor was identified through absorption and scattering images. Tumor shrinkage was observed during the course of chemotherapy from all the optical images. Our results show that oxy-hemoglobin, deoxy-hemoglobin and total hemoglobin in tumor decreased after chemotherapy compared to that of before chemotherapy. Significant changes in tumor refractive index along with tumor cellular morphology during the entire chemotherapy are also observed.

Gadd34 Requirement for Normal Hemoglobin Synthesis

PubMed Central

Patterson, Andrew D.; Hollander, M. Christine; Miller, Georgina F.; Fornace, Albert J.

2006-01-01

The protein encoded by growth arrest and DNA damage-inducible transcript 34 (Gadd34) is associated with translation initiation regulation following certain stress responses. Through interaction with the protein phosphatase 1 catalytic subunit (PP1c), Gadd34 recruits PP1c for the removal of an inhibitory phosphate group on the α subunit of elongation initiation factor 2, thereby reversing the shutoff of protein synthesis initiated by stress-inducible kinases. In the absence of stress, the physiologic consequences of Gadd34 function are not known. Initial analysis of Gadd34-null mice revealed several significant findings, including hypersplenism, decreased erythrocyte volume, increased numbers of circulating erythrocytes, and decreased hemoglobin content, resembling some thalassemia syndromes. Biochemical analysis of the hemoglobin-producing reticulocyte (an erythrocyte precursor) revealed that the decreased hemoglobin content in the Gadd34-null erythrocyte is due to the reduced initiation of the globin translation machinery. We propose that an equilibrium state exists between Gadd34/PP1c and the opposing heme-regulated inhibitor kinase during hemoglobin synthesis in the reticulocyte. PMID:16478986

Activity of Brazilian propolis against Aeromonas hydrophila and its effect on Nile tilapia growth, hematological and non-specific immune response under bacterial infection.

PubMed

Orsi, Ricardo O; Santos, Vivian G Dos; Pezzato, Luiz E; Carvalho, Pedro L P F DE; Teixeira, Caroline P; Freitas, Jakeline M A; Padovani, Carlos R; Sartori, Maria M P; Barros, Margarida M

2017-01-01

The effect of the ethanolic extract of propolis (EEP) on Aeromonas hydrophila was analyzed by determination of minimum inhibitory concentration (MIC). Then, the effects of crude propolis powder (CPP) on growth, hemato-immune parameters of the Nile tilapia, as well as its effects on resistance to A. hydrophila challenge were investigated. The CPP (0.5, 1.0, 1.5, 2.0, 2.5 and 3.0%) was added to the diet of 280 Nile tilapia (50.0 ± 5.7 g fish-1). Hemato-immune parameters were analyzed before and after the bacterial challenge. Red blood cell, hematocrit, hemoglobin, mean corpuscular volume (MCV), mean corpuscular hemoglobin concentration (MCHC), and hydrogen peroxide (H2O2) and nitric oxide (NO) were evaluated. The MIC of the EEP was 13% (v/v) with a bactericidal effect after 24 hours. Growth performance was significantly lower for those fish fed diets containing 2.5 and 3% of CPP compared to the control diet. Differences in CPP levels affected fish hemoglobin, neutrophils number and NO following the bacterial challenge. For others parameters no significant differences were observed. Our results show that although propolis has bactericidal properties in vitro, the addition of crude propolis powder to Nile tilapia extruded diets does not necessarily lead to an improvement of fish health.

[Analysis of hematological phenotype and genotype of 23 patients from Guangdong with co-inherited hemoglobin Hb Westmead and β-thalassemia].

PubMed

Yan, Miansheng; Gan, Xin; Liu, Min; Huang, Bin; Zhong, Liangying

2016-10-01

To analyze the genotype-phenotype correlation among carriers from Guangdong with co-inherited hemoglobin Hb Westmead (HbWS) and β-thalassemia. Twenty three patients (including 9 males and 14 females, aged 1-53 year old) were diagnosed by hematological analysis and genetic testing. Complete blood cell count and hemoglobin electrophoresis analysis were performed on a XE4000i automatic hemocyte analyzer. Hb, HbF and HbA2 were tested by high performance liquid chromatography (HPLC). Gap-PCR was adopted to detect three common thalassemia deletions. Reverse dot-blotting (RDB) assay was applied for detecting three common non-deletional α2 gene mutations and β-thalassemia. Among the 23 patients, 12 showed anemia, among whom 9 had mild anemia and 3 had moderate anemia. The lowest Hb was 68 g/L, and both mean corpuscular volume and mean corpuscular hemoglobin were lower than average, while HbA2 was higher than 3.5%. Genetic analysis confirmed that 5 cases had αWS-α/α-α, β CD654/β N (21.7%), 4 had α WS-α/α-α, β CD41-42/β N (17.4%), 5 had α WS-α/α-α, β CD17/β N (21.7%), 4 had α WS-α/α-α, β CD28/β N (17.4%), 1 had α WS-α/α-α, β CD71-72/β N (4.3%), 1 had αWS-α/α-α, β CD27-28/β N (4.3%), 1 had α WS-α/α-α, β CD41-42/β CD17 (4.3%), 2 had a concomitant β-thalassemia heterozygosity and -α 3.7 deletion. Patients with co-existing Hb WS and other β-thalassemia trait may show variable clinical features. Such compound heterozygotes are usually misdiagnosed during screening by hemoglobin electrophoresis, accurate diagnose should be attained by molecular diagnosis.

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.

Association between sickle cell and β-thalassemia genes and hemoglobin concentration and anemia in children and non-pregnant women in Sierra Leone: ancillary analysis of data from Sierra Leone's 2013 National Micronutrient Survey.

PubMed

Wirth, James P; Ansumana, Rashid; Woodruff, Bradley A; Koroma, Aminata S; Hodges, Mary H

2018-01-17

By measuring the associations between the presence of sickle cell and β-thalassemia genes, we assessed the extent to which these hemoglobinopathies contribute to the high prevalence of anemia observed in preschool-aged children and women of reproductive age in Sierra Leone. The prevalence of anemia was statistically significantly higher in children with homozygous sickle cell genes (HbSS) than in children with normal hemoglobin genes (HbAA or HbAC), but there was no difference in anemia prevalence in those with heterozygous sickle cell trait (HbAS or HbSC) compared with those with normal hemoglobin genes. In women, there was no difference in anemia prevalence by sickle cell status. In both children and women, there was no difference in the anemia prevalence for individuals with or without the β-thalassemia gene. For both sickle cell and β-thalassemia, there was no significant difference in hemoglobin concentrations by sickle cell or β-thalassemia status. Anemia prevalence was higher in children and women with homozygous sickle cell (HbSS). However, as the prevalence of HbSS children (5.4%) and women (1.6%) was quite small, it is unlikely that these hemoglobinopathies substantially contributed to the high anemia prevalence found in the 2013 national micronutrient survey.

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.

The Effects of Ethanol on the Morphological and Biochemical Properties of Individual Human Red Blood Cells.

PubMed

Lee, Sang Yun; Park, Hyun Joo; Best-Popescu, Catherine; Jang, Seongsoo; Park, Yong Keun

2015-01-01

Here, we report the results of a study on the effects of ethanol exposure on human red blood cells (RBCs) using quantitative phase imaging techniques at the level of individual cells. Three-dimensional refractive index tomograms and dynamic membrane fluctuations of RBCs were measured using common-path diffraction optical tomography, from which morphological (volume, surface area, and sphericity); biochemical (hemoglobin (Hb) concentration and Hb content); and biomechanical (membrane fluctuation) parameters were retrieved at various concentrations of ethanol. RBCs exposed to the ethanol concentration of 0.1 and 0.3% v/v exhibited cell sphericities higher than those of normal cells. However, mean surface area and sphericity of RBCs in a lethal alcoholic condition (0.5% v/v) are not statistically different with those of healthy RBCs. Meanwhile, significant decreases of Hb content and concentration in RBC cytoplasm at the lethal condition were observed. Furthermore, dynamic fluctuation of RBC membranes increased significantly upon ethanol treatments, indicating ethanol-induced membrane fluidization.

Bioactive natural constituents from lemongrass tea and erythropoiesis boosting effects: potential use in prevention and treatment of anemia.

PubMed

Ekpenyong, Christopher E; Daniel, Nyebuk E; Antai, Atim B

2015-01-01

This study assessed the effects of lemongrass (Cymbopogon citratus) tea on hematologic indices in human volunteers. One hundred five subjects (55 men and 50 women), aged 18 to 35 years, were randomly assigned to groups set to orally receive infusion prepared from 2, 4, or 8 g of C. citratus leaves once daily for 30 days. Assessment of hematologic indices (hemoglobin concentration [Hb], packed cell volume [PCV], red blood cell [RBC] count, mean cell Hb [MCH], mean cell volume [MCV], mean cell Hb concentration [MCHC], total white blood cell [WBC-total] and differentials, and platelets) were performed 1 day before (baseline), and at 10 (acute) and 30 days (subchronic phase) after the initiation of treatment. Results obtained on days 10 and 30 were compared with baseline values. Infusions prepared from C. citratus leaf powder, which tested positive for tannins, saponins, alkaloids, flavonoids, macro- and micronutrients, significantly increased PCV, Hb, and RBC (P<.05) in all subjects, particularly in the subchronic phase of the study. MCH, MCV, and MCHC were not significantly different from baseline values in both the sexes. WBCs and differentials significantly decreased (P<.05) with the exception of neutrophils and lymphocytes, which significantly increased in some or all groups (P<.05), respectively. C. citratus leaf infusion appears to exert an erythropoiesis boosting effect, likely due to some nutritional constituents and its antioxidant and pharmacologic properties.

Exploring the relationship of peripheral total bilirubin, red blood cell, and hemoglobin with blood pressure during childhood and adolescence.

PubMed

Chen, Xiao-Tian; Yang, Song; Yang, Ya-Ming; Zhao, Hai-Long; Chen, Yan-Chun; Zhao, Xiang-Hai; Wen, Jin-Bo; Tian, Yuan-Rui; Yan, Wei-Li; Shen, Chong

2017-11-04

Total bilirubin is beneficial for protecting cardiovascular diseases in adults. The authors aimed to investigate the association of total bilirubin, red blood cell, and hemoglobin levels with the prevalence of high blood pressure in children and adolescents. A total of 3776 students (aged from 6 to 16 years old) were examined using cluster sampling. Pre-high blood pressure and high blood pressure were respectively defined as the point of 90th and 95th percentiles based on the Fourth Report on the Diagnosis, Evaluation, and Treatment of High Blood Pressure in Children and Adolescents. Both systolic and diastolic blood pressure were standardized into z-scores. Peripheral total bilirubin, red blood cell and hemoglobin levels were significantly correlated with age, and also varied with gender. Peripheral total bilirubin was negatively correlated with systolic blood pressure in 6- and 9-year-old boys, whilst positively correlated with diastolic blood pressure in the 12-year-old boys and 13- to 15-year-old girls (p<0.05). Higher levels of red blood cell and hemoglobin were observed in pre-high blood pressure and high blood pressure students when compared with their normotensive peers (p<0.01). The increases in red blood cell and hemoglobin were significantly associated with high blood pressure after adjusting for confounding factors. The ORs (95% CI) of each of the increases were 2.44 (1.52-3.92) and 1.04 (1.03-1.06), respectively. No statistical association between total bilirubin and high blood pressure was observed (p>0.05). Total bilirubin could be weakly correlated with both systolic and diastolic blood pressure, as correlations varied with age and gender in children and adolescents; in turn, the increased levels of red blood cell and hemoglobin are proposed to be positively associated with the prevalence of high blood pressure. Copyright © 2017 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

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

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

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

2012-01-01

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

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

PubMed

Starodub, N F

1980-01-01

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

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

USDA-ARS?s Scientific Manuscript database

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

Staphylococcus aureus IsdB Is a Hemoglobin Receptor Required for Heme Iron Utilization▿

PubMed Central

Torres, Victor J.; Pishchany, Gleb; Humayun, Munir; Schneewind, Olaf; Skaar, Eric P.

2006-01-01

The pathogenesis of human infections caused by the gram-positive microbe Staphylococcus aureus has been previously shown to be reliant on the acquisition of iron from host hemoproteins. The iron-regulated surface determinant system (Isd) encodes a heme transport apparatus containing three cell wall-anchored proteins (IsdA, IsdB, and IsdH) that are exposed on the staphylococcal surface and hence have the potential to interact with human hemoproteins. Here we report that S. aureus can utilize the host hemoproteins hemoglobin and myoglobin, but not hemopexin, as iron sources for bacterial growth. We demonstrate that staphylococci capture hemoglobin on the bacterial surface via IsdB and that inactivation of isdB, but not isdA or isdH, significantly decreases hemoglobin binding to the staphylococcal cell wall and impairs the ability of S. aureus to utilize hemoglobin as an iron source. Stable-isotope-tracking experiments revealed removal of heme iron from hemoglobin and transport of this compound into staphylococci. Importantly, mutants lacking isdB, but not isdH, display a reduction in virulence in a murine model of abscess formation. Thus, IsdB-mediated scavenging of iron from hemoglobin represents an important virulence strategy for S. aureus replication in host tissues and for the establishment of persistent staphylococcal infections. PMID:17041042

Digital PCR analysis of maternal plasma for noninvasive detection of sickle cell anemia.

PubMed

Barrett, Angela N; McDonnell, Thomas C R; Chan, K C Allen; Chitty, Lyn S

2012-06-01

Cell-free fetal DNA (cffDNA) constitutes approximately 10% of the cell-free DNA in maternal plasma and is a suitable source of fetal genetic material for noninvasive prenatal diagnosis (NIPD). The objective of this study was to determine the feasibility of using digital PCR for NIPD in pregnancies at risk of sickle cell anemia. Minor-groove binder (MGB) TaqMan probes were designed to discriminate between wild-type hemoglobin A and mutant (hemoglobin S) alleles encoded by the HBB (hemoglobin, beta) gene in cffDNA isolated from maternal plasma samples obtained from pregnancies at risk of sickle cell anemia. The fractional fetal DNA concentration was assessed in male-bearing pregnancies with a digital PCR assay for the Y chromosome-specific marker DYS14. In pregnancies with a female fetus, a panel of biallelic insertion/deletion polymorphism (indel) markers was developed for the quantification of the fetal DNA fraction. We used digital real-time PCR to analyze the dosage of the variant encoding hemoglobin S relative to that encoding wild-type hemoglobin A. The sickle cell genotype was correctly determined in 82% (37 of 45) of male fetuses and 75% (15 of 20) of female fetuses. Mutation status was determined correctly in 100% of the cases (25 samples) with fractional fetal DNA concentrations >7%. The panel of indels was informative in 65% of the female-bearing pregnancies. Digital PCR can be used to determine the genotype of fetuses at risk for sickle cell anemia. Optimization of the fractional fetal DNA concentration is essential. More-informative indel markers are needed for this assay's comprehensive use in cases of a female fetus.

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

PubMed

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

2015-01-01

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

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.

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.

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

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.

Atomic detail brownian dynamics simulations of concentrated protein solutions with a mean field treatment of hydrodynamic interactions.

PubMed

Mereghetti, Paolo; Wade, Rebecca C

2012-07-26

High macromolecular concentrations are a distinguishing feature of living organisms. Understanding how the high concentration of solutes affects the dynamic properties of biological macromolecules is fundamental for the comprehension of biological processes in living systems. In this paper, we describe the implementation of mean field models of translational and rotational hydrodynamic interactions into an atomically detailed many-protein brownian dynamics simulation method. Concentrated solutions (30-40% volume fraction) of myoglobin, hemoglobin A, and sickle cell hemoglobin S were simulated, and static structure factors, oligomer formation, and translational and rotational self-diffusion coefficients were computed. Good agreement of computed properties with available experimental data was obtained. The results show the importance of both solvent mediated interactions and weak protein-protein interactions for accurately describing the dynamics and the association properties of concentrated protein solutions. Specifically, they show a qualitative difference in the translational and rotational dynamics of the systems studied. Although the translational diffusion coefficient is controlled by macromolecular shape and hydrodynamic interactions, the rotational diffusion coefficient is affected by macromolecular shape, direct intermolecular interactions, and both translational and rotational hydrodynamic interactions.

A clinical analysis of erythrocytapheresis for the treatment of polycythemia.

PubMed

Liu, Huasheng; Liu, Haibo; Shen, Jingzhi; Sun, Chunhong; Guo, Caili; Lin, Huan; Yao, Jianna; Ma, Rui; Zhang, Mei

2013-04-01

To evaluate the efficacy and safety of erythrocytapheresis (ECP) in the treatment of polycythemia. Patients diagnosed with polycythemia were included in this retrospective analysis and treated with ECP (n=20) or conventional treatments (exsanguination; n=20). Blood laboratory values and adverse effects were recorded. In ECP-treated patients mean red blood cell (RBC) collection time was 25.7±4.5min (range: 19-37min), with a mean collection volume of 773.5±129.3mL (range: 600-1002mL). From baseline, ECP reduced the mean number of RBCs (0.6×10(12)/L [7.6%]), mean hemoglobin (31.1g/L [14.8%]), and mean hematocrit (13.1% [20.2%]) (P<0.001 for each). After ECP, a marked reduction in symptoms associated with polycythemia was also observed. Treatment of patients with polycythemia using ECP reduces RBC count, hemoglobin, and hematocrit. The advantages associated with ECP over conventional therapy should be considered when choosing a treatment plan for patients with polycythemia. Copyright © 2013. Published by Elsevier Ltd.

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

PubMed Central

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

2015-01-01

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

Spirometry, Static Lung Volumes, and Diffusing Capacity.

PubMed

Vaz Fragoso, Carlos A; Cain, Hilary C; Casaburi, Richard; Lee, Patty J; Iannone, Lynne; Leo-Summers, Linda S; Van Ness, Peter H

2017-09-01

Spirometric Z-scores from the Global Lung Initiative (GLI) rigorously account for age-related changes in lung function and are thus age-appropriate when establishing spirometric impairments, including a restrictive pattern and air-flow obstruction. However, GLI-defined spirometric impairments have not yet been evaluated regarding associations with static lung volumes (total lung capacity [TLC], functional residual capacity [FRC], and residual volume [RV]) and gas exchange (diffusing capacity). We performed a retrospective review of pulmonary function tests in subjects ≥40 y old (mean age 64.6 y), including pre-bronchodilator measures for: spirometry ( n = 2,586), static lung volumes by helium dilution with inspiratory capacity maneuver ( n = 2,586), and hemoglobin-adjusted single-breath diffusing capacity ( n = 2,508). Using multivariable linear regression, adjusted least-squares means (adj LS Means) were calculated for TLC, FRC, RV, and hemoglobin-adjusted single-breath diffusing capacity. The adj LS Means were expressed with and without height-cubed standardization and stratified by GLI-defined spirometry, including normal ( n = 1,251), restrictive pattern ( n = 663), and air-flow obstruction (mild, [ n = 128]; moderate, [ n = 150]; and severe, [ n = 394]). Relative to normal spirometry, restrictive-pattern had lower adj LS Means for TLC, FRC, RV, and hemoglobin-adjusted single-breath diffusing capacity ( P ≤ .001). Conversely, relative to normal spirometry, mild, moderate, and severe air-flow obstruction had higher adj LS Means for FRC and RV ( P < .001). However, only mild and moderate air-flow obstruction had higher adj LS Means for TLC ( P < .001), while only moderate and severe air-flow obstruction had higher adj LS Means for RV/TLC ( P < .001) and lower adj LS Means for hemoglobin-adjusted single-breath diffusing capacity ( P < .001). Notably, TLC (calculated as FRC + inspiratory capacity) was not increased in severe air-flow obstruction ( P ≥ .11) because inspiratory capacity decreased with increasing air-flow obstruction ( P < .001), thus opposing the increased FRC ( P < .001). Finally, P values were similar whether adj LS Means were height-cubed standardized. A GLI-defined spirometric restrictive pattern is strongly associated with a restrictive ventilatory defect (decreased TLC, FRC, and RV), while GLI-defined spirometric air-flow obstruction is strongly associated with hyperinflation (increased FRC) and air trapping (increased RV and RV/TLC). Both spirometric impairments were strongly associated with impaired gas exchange (decreased hemoglobin-adjusted single-breath diffusing capacity). Copyright © 2017 by Daedalus Enterprises.

A Biphasic Change of Regional Blood Volume in the Frontal Cortex during Non-Rapid Eye Movement Sleep: A Near-Infrared Spectroscopy Study.

PubMed

Zhang, Zhongxing; Khatami, Ramin

2015-08-01

Current knowledge on hemodynamics in sleep is limited because available techniques do not allow continuous recordings and mainly focus on cerebral blood flow while neglecting other important parameters, such as blood volume (BV) and vasomotor activity. Observational study. Continuous measures of hemodynamics over the left forehead and biceps were performed using near-infrared spectroscopy (NIRS) during nocturnal polysomnography in 16 healthy participants in sleep laboratory. Temporal dynamics and mean values of cerebral and muscular oxygenated hemoglobin (HbO2), deoxygenated hemoglobin (HHb), and BV during different sleep stages were compared. A biphasic change of cerebral BV was observed which contrasted a monotonic increase of muscular BV during non-rapid eye movement sleep. A significant decrement in cerebral HbO2 and BV accompanied by an increase of HHb was recorded at sleep onset (Phase I). Prior to slow wave sleep (SWS) HbO2 and BV turned to increase whereas HHb began to decrease in subsequent Phase II suggested increased brain perfusion during SWS. The cerebral HbO2 slope correlated to BV slope in Phase I and II, but it only correlated to HHb slope in Phase II. The occurrence time of inflection points correlated to SWS latencies. Initial decrease of brain perfusion with decreased blood volume (BV) and oxygenated hemoglobin (HbO2) together with increasing muscular BV fit thermoregulation process at sleep onset. The uncorrelated and correlated slopes of HbO2 and deoxygenated hemoglobin indicate different mechanisms underlying the biphasic hemodynamic process in light sleep and slow wave sleep (SWS). In SWS, changes in vasomotor activity (i.e., increased vasodilatation) may mediate increasing cerebral and muscular BV. © 2015 Associated Professional Sleep Societies, LLC.

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

PubMed Central

Yang, Liqing; Du, Shuai; Sun, Yuefeng

2017-01-01

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

Anemia in patients with coinherited thalassemia and glucose-6-phosphate dehydrogenase deficiency.

PubMed

Pornprasert, Sakorn; Phanthong, Siratcha

2013-01-01

Thalassemia and glucose-6-phosphate dehydrogenase (G-6-PD) deficiency are genetic disorders that cause hemolytic anemia. In areas with high frequencies of both hematological disorders, coinheritance of G-6-PD deficiency with thalassemia can be found. Whether G-6-PD deficiency, coinherited with thalassemia, enhances severe anemia is still unclear. Hematological parameters between thalassemia carriers with G-6-PD deficiency and those without G-6-PD deficiency were compared. The G-6-PD deficiency was diagnosed in 410 blood samples from thalassemia patients using a fluorescent spot test. The levels of hemoglobin (Hb), packed cell volume (PCV), mean corpuscular volume (MCV) and Hb A2/Hb E [β26(B8)Glu→Lys; HBB: c.79G>A] were measured using an automated blood counter and high performance liquid chromatography (HPLC), respectively. The G-6-PD deficiency was found in 37 samples (9.02%). Mean levels of Hb, PCV, MCV and Hb A2/E were similar between the two groups. Thus, G-6-PD deficiency did not enhance red blood cell pathology or induce more anemic severity in thalassemia patients.

Iron deficiency alters megakaryopoiesis and platelet phenotype independent of thrombopoietin.

PubMed

Evstatiev, Rayko; Bukaty, Adam; Jimenez, Kristine; Kulnigg-Dabsch, Stefanie; Surman, Lidia; Schmid, Werner; Eferl, Robert; Lippert, Kathrin; Scheiber-Mojdehkar, Barbara; Kvasnicka, Hans Michael; Khare, Vineeta; Gasche, Christoph

2014-05-01

Iron deficiency is a common cause of reactive thrombocytosis, however, the exact pathways have not been revealed. Here we aimed to study the mechanisms behind iron deficiency-induced thrombocytosis. Within few weeks, iron-depleted diet caused iron deficiency in young Sprague-Dawley rats, as reflected by a drop in hemoglobin, mean corpuscular volume, hepatic iron content and hepcidin mRNA in the liver. Thrombocytosis established in parallel. Moreover, platelets produced in iron deficient animals displayed a higher mean platelet volume and increased aggregation. Bone marrow studies revealed subtle alterations that are suggestive of expansion of megakaryocyte progenitors, an increase in megakaryocyte ploidy and accelerated megakaryocyte differentiation. Iron deficiency did not alter the production of hematopoietic growth factors such as thrombopoietin, interleukin 6 or interleukin 11. Megakaryocytic cell lines grown in iron-depleted conditions exhibited reduced proliferation but increased ploidy and cell size. Our data suggest that iron deficiency increases megakaryopoietic differentiation and alters platelet phenotype without changes in megakaryocyte growth factors, specifically TPO. Iron deficiency-induced thrombocytosis may have evolved to maintain or increase the coagulation capacity in conditions with chronic bleeding. Copyright © 2014 Wiley Periodicals, Inc.

PARTITIONING OF BENZENE IN SICKLE CELL BLOOD AND NORMAL BLOOD AND IN THE BLOOD OF THE GUINEA PIG, MOUSE, AND RAT

EPA Science Inventory

Abstract
Benzene was used as a prototypic volatile organic chemical to ascertain whether the insoluble form of hemoglobin (HbS) from subjects with homozygous sickle cell disease (SCD) has a greater VOC carrying capacity than hemoglobin (Hb) from normal subjects (HbA) which is ...

Modulation of sickle cell crisis by naturally occurring band 3 specific antibodies -- a malaria link.

PubMed

Kennedy, James Randall

2002-05-01

This paper's focus is prevention of sickle cell adhesion resulting from the erythrocyte's prematurely denatured hemoglobin. This denatured hemoglobin causes a molecule called band 3 to cluster on the erythrocyte's surface and adhere to the CD36 molecule located on the microvascular endothelium. Natural antibodies recognize these clusters on senescent erythrocytes and prevent their endothelial adhesion and target them for reticuloendothelial elimination. Band 3 is also displayed on the erythrocytes of individuals with falciparum malaria and the vaso-occlusive pathology in these patients is prevented in individuals with sickle trait. The hypothesis is that prematurely denatured sickle hemoglobin results in an up regulation of natural antibodies which control erythrocyte adhesion in both malaria and sickle cell disease.

[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.

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.

Evaluation of nonsurgical periodontal therapy in chronic periodontitis patients with anemia by estimating hematological parameters and high-sensitivity C-reactive protein levels

PubMed Central

Musalaiah, S. V. V. S.; Anupama, M.; Nagasree, M.; Krishna, Ch. Murali; Kumar, Aravind; Kumar, P. Mohan

2014-01-01

Background: Periodontal tissues mount an immune inflammatory response to bacteria and their products. Certain inflammatory cytokines produced during periodontal inflammation increase the production of acute phase proteins like high‑sensitivity C‑reactive protein (hs‑CRP) and can depress erythropoietin production leading to the development of anemia. Aim: The aim of this study is to investigate the efficacy of nonsurgical periodontal therapy on red blood cell (RBC) parameters and hs-CRP in chronic periodontitis patients with anemia. Materials and Methods: This is a longitudinal, interventional study with 6-month follow-up. A total of 30 subjects with anemia and chronic periodontitis with age group of 33-55 years were selected by screening hemoglobin (Hb) levels and examining periodontal findings. The clinical parameters plaque index (PI), gingival index (GI), probing pocket depth (PPD) and clinical attachment level (CAL) were recorded at baseline. Laboratory blood investigations were performed to evaluate RBC count, Hb, packed cell volume (PCV), erythrocyte sedimentation rate (ESR) and red cell indices, hs-CRP at baseline. Nonsurgical periodontal therapy was performed for all patients. Patients were recalled after 6 months. The clinical and hematological parameters were re-evaluated to analyze the changes after nonsurgical periodontal therapy. Results: The results showed that there was a significant increase in Hb levels, RBC count and PCV from baseline to 6 months after nonsurgical periodontal therapy. There is significant decrease in levels of ESR and hs-CRP levels after nonsurgical periodontal therapy indicating resolution of periodontal inflammation. There is a significant decrease in PPD, scores of PI and GI and significant increase in CAL gain. Minimal changes in mean corpuscular volume, mean corpuscular hemoglobin (MCH) and MCH concentration indicated that the lower values of red cell parameters are not due to any vitamin and mineral deficiencies, but secondary to the chronic inflammatory changes associated with chronic periodontal disease. Conclusion: The present study strengthens the hypothesis that chronic periodontitis may lead to anemia and provides evidence that nonsurgical periodontal therapy can improve the anemic status and reduce levels of hs-CRP in patients with chronic periodontitis. PMID:25210388

Evaluation of nonsurgical periodontal therapy in chronic periodontitis patients with anemia by estimating hematological parameters and high-sensitivity C-reactive protein levels.

PubMed

Musalaiah, S V V S; Anupama, M; Nagasree, M; Krishna, Ch Murali; Kumar, Aravind; Kumar, P Mohan

2014-07-01

Periodontal tissues mount an immune inflammatory response to bacteria and their products. Certain inflammatory cytokines produced during periodontal inflammation increase the production of acute phase proteins like high‑sensitivity C‑reactive protein (hs‑CRP) and can depress erythropoietin production leading to the development of anemia. The aim of this study is to investigate the efficacy of nonsurgical periodontal therapy on red blood cell (RBC) parameters and hs-CRP in chronic periodontitis patients with anemia. This is a longitudinal, interventional study with 6-month follow-up. A total of 30 subjects with anemia and chronic periodontitis with age group of 33-55 years were selected by screening hemoglobin (Hb) levels and examining periodontal findings. The clinical parameters plaque index (PI), gingival index (GI), probing pocket depth (PPD) and clinical attachment level (CAL) were recorded at baseline. Laboratory blood investigations were performed to evaluate RBC count, Hb, packed cell volume (PCV), erythrocyte sedimentation rate (ESR) and red cell indices, hs-CRP at baseline. Nonsurgical periodontal therapy was performed for all patients. Patients were recalled after 6 months. The clinical and hematological parameters were re-evaluated to analyze the changes after nonsurgical periodontal therapy. The results showed that there was a significant increase in Hb levels, RBC count and PCV from baseline to 6 months after nonsurgical periodontal therapy. There is significant decrease in levels of ESR and hs-CRP levels after nonsurgical periodontal therapy indicating resolution of periodontal inflammation. There is a significant decrease in PPD, scores of PI and GI and significant increase in CAL gain. Minimal changes in mean corpuscular volume, mean corpuscular hemoglobin (MCH) and MCH concentration indicated that the lower values of red cell parameters are not due to any vitamin and mineral deficiencies, but secondary to the chronic inflammatory changes associated with chronic periodontal disease. The present study strengthens the hypothesis that chronic periodontitis may lead to anemia and provides evidence that nonsurgical periodontal therapy can improve the anemic status and reduce levels of hs-CRP in patients with chronic periodontitis.

[Iron nutritional status in pregnant adolescents at the beginning of gestation].

PubMed

Hertrampf, E; Olivares, M; Letelier, A; Castillo, C

1994-12-01

The frequency of anemia and iron nutrition deficiency was assessed in 342 low socioeconomic level pregnant teenagers at entry to prenatal care in 5 outpatient clinics from a South Orient area of Santiago Chile. According to the Center for Disease Control Criteria, 1.2% of women had iron deficiency anemia. Iron stores were insufficient (defined as a serum ferritin lower than 20 g/L) in 55% for women and depleted (serum ferritin lower than 10 g/L) in 21%. Women with more than 14 weeks of gestation had lower packed red cell volumes, hemoglobin, mean corpuscular volumes and ferritin levels than women with less than 14 of gestation. It is concluded that the prevalence of iron deficiency anemia is lower than that predicted for a highly vulnerable group but the high frequency of low iron stores should encourage the use of iron supplementation in these teenagers.

Low midpregnancy placental volume in rural Indian women: A cause for low birth weight?

PubMed

Kinare, A S; Natekar, A S; Chinchwadkar, M C; Yajnik, C S; Coyaji, K J; Fall, C H; Howe, D T

2000-02-01

We sought to study midpregnancy placental volume in rural Indian women, its maternal determinants, and its relationship to neonatal size. We performed a prospective community-based study of maternal nutrition and fetal growth in 6 villages near the city of Pune. Measurements included midpregnancy placental volume determined by means of ultrasonography at 15 to 18 weeks' gestation, maternal anthropometric measurements before and during pregnancy, and maternal blood pressure and biochemical parameters during pregnancy. Neonatal size and placental weight were measured at birth. The mothers were short and underweight (mean height, 1.52 m; weight, 42 kg; body mass index, 18 kg/m(2)) and produced small babies (mean birth weight, 2648 g). Midpregnancy placental volume (median, 144 mL) was related to the mother's prepregnancy weight (r = 0.15; P <.001) but not to weight gain during pregnancy, blood pressure, or circulating hemoglobin, ferritin, red blood cell folate, or glucose concentrations. Midpregnancy placental volume was related to placental weight at birth (r = 0.29; P <.001) and birth weight (r = 0.25; P <.001) independent of maternal size. In Indian mothers midpregnancy placental volume is significantly associated with prepregnant maternal weight and is an independent predictor of birth weight. Our findings may provide clues to the high prevalence of low-birth-weight infants in India.

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

[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.

Influences of red blood cell and platelet counts on the distribution and elimination of crystalloid fluid.

PubMed

Hahn, Robert G

2017-01-01

A high number of blood cells increases the viscosity of the blood. The present study explored whether variations in blood cell counts are relevant to the distribution and elimination of infused crystalloid fluid. On three different occasions, 10 healthy male volunteers received an intravenous infusion of 25mL/kg of Ringer's acetate, Ringer's lactate, and isotonic saline over 30min. Blood hemoglobin and urinary excretion were monitored for 4h and used as input in a two-volume kinetic model, using nonlinear mixed effects software. The covariates used in the kinetic model were red blood cell and platelet counts, the total leukocyte count, the use of isotonic saline, and the arterial pressure. Red blood cell and platelet counts in the upper end of the normal range were associated with a decreased rate of distribution and redistribution of crystalloid fluid. Simulations showed that high counts were correlated with volume expansion of the peripheral (interstitial) fluid space, while the plasma volume was less affected. In contrast, the total leukocyte count had no influence on the distribution, redistribution, or elimination. The use of isotonic saline caused a transient reduction in the systolic arterial pressure (P<0.05) and doubled the half-life of infused fluid in the body when compared to the two Ringer solutions. Isotonic saline did not decrease the serum potassium concentration, despite the fact that saline is potassium-free. High red blood cell and platelet counts are associated with peripheral accumulation of infused crystalloid fluid. Copyright © 2017 The Lithuanian University of Health Sciences. Production and hosting by Elsevier Sp. z o.o. All rights reserved.

Selected terpenes from leaves of Ocimum basilicum L. induce hemoglobin accumulation in human K562 cells.

PubMed

Feriotto, Giordana; Marchetti, Nicola; Costa, Valentina; Torricelli, Piera; Beninati, Simone; Tagliati, Federico; Mischiati, Carlo

2018-06-01

Re-expression of fetal hemoglobin (HbF) was proposed as a possible therapeutic strategy for β-haemoglobinopathies. Although several inducers of HbF were tested in clinical trials, only hydroxyurea (HU) received FDA approval. Despite it produced adequate HbF levels only in half of HU-treated SCD patients, and was ineffective at all in β-thalassemia patients, beneficial effects of this approach suggested to continue in this direction identifying further molecules capable of inducing HbF. We tested the potential of essential oil isolated from Ocimum basilicum L. leaves (ObEO) in inducing hemoglobin biosynthesis. Initially, dose-dependent effect and kinetics of hemoglobin accumulation in K562 cells after treatment with ObEO were evaluated. ObEO induced dose-dependent hemoglobin accumulation superior to hydroxyurea and rapamycin and a strongest γ-globin mRNA expression. Terpenes composition of ObEO was studied by GC-MS. Three main constituents, linalool, eugenol and eucalyptol, represented about 75% of total. A blend of these three terpenes fully replicated the ObEO's biological effect, thus indicating that one of them or all together could be the active ingredients. When terpenes were tested individually, eugenol was the only one inducing stable hemoglobin accumulation, while eucalyptol and linalool produced only a small transient response. However, eugenol potential was strongly enhanced in the presence of eucalyptol and linalool, suggesting a synergistic effect on hemoglobin accumulation. By these results, the discovery of a new inducer and the interesting activity of a blend of major terpenes from ObOE on Hb accumulation could have positive fallouts on β-thalassemia and sickle cells anemia. Copyright © 2018 Elsevier B.V. All rights reserved.

[Heme-iron in the human body].

PubMed

Balla, József; Balla, György; Lakatos, Béla; Jeney, Viktória; Szentmihályi, Klára

2007-09-09

Iron is essential for all living organism, although in excess amount it is dangerous via catalyzing the formation of reactive oxygen species. Absorption of iron is strictly controlled resulting in a fine balance of iron-loss and iron-uptake. In countries where the ingestion of heme-iron is significant by meal, great part of iron content in the body originates from heme. Heme derived from food is absorbed by a receptor-mediated manner by enterocytes of small intestine then it is degraded in a reaction catalyzed by heme oxygenase. Iron released from the porphyrin ring leaves enterocytes as transferrin associated iron. Prosthetic group of several proteins contains heme, therefore, it is synthesized by all cells. One of the most significant heme proteins is hemoglobin which transports oxygen in the erythrocytes. Hemoglobin released from erythrocyte during intravascular hemolysis binds to haptoglobin and is taken up by cells of the monocyte-macrophage lineage. Oxidation of hemoglobin (ferro) to methemoglobin (ferri) is inhibited by the structure of hemoglobin although it is not hindered. Superoxide anion is also formed in the reaction that initiates further free radical reactions. In contrast to ferrohemoglobin, methemoglobin readily releases heme, therefore, oxidation of hemoglobin drives the formation of free heme in plasma. Heme binds to a plasma protein, hemopexin, and is internalized by cells of monocyte-macrophage lineage in a receptor-mediated manner, then degraded in reaction catalysed by heme oxygenase. Heme is also taken up by plasma lipoproteins and endothelial cells leading to oxidation of LDL and subsequent endothelial cell damage. The purpose of this work was to summarize the processes related to heme.

Porphyromonas endodontalis binds, reduces and grows on human hemoglobin.

PubMed

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

2001-08-01

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

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

PubMed Central

Wilber, Andrew; Nienhuis, Arthur W.

2011-01-01

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

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.

Evaluating visibility of age spot and freckle based on simulated spectral reflectance distribution and facial color image

NASA Astrophysics Data System (ADS)

Hirose, Misa; Toyota, Saori; Tsumura, Norimichi

2018-02-01

In this research, we evaluate the visibility of age spot and freckle with changing the blood volume based on simulated spectral reflectance distribution and the actual facial color images, and compare these results. First, we generate three types of spatial distribution of age spot and freckle in patch-like images based on the simulated spectral reflectance. The spectral reflectance is simulated using Monte Carlo simulation of light transport in multi-layered tissue. Next, we reconstruct the facial color image with changing the blood volume. We acquire the concentration distribution of melanin, hemoglobin and shading components by applying the independent component analysis on a facial color image. We reproduce images using the obtained melanin and shading concentration and the changed hemoglobin concentration. Finally, we evaluate the visibility of pigmentations using simulated spectral reflectance distribution and facial color images. In the result of simulated spectral reflectance distribution, we found that the visibility became lower as the blood volume increases. However, we can see that a specific blood volume reduces the visibility of the actual pigmentations from the result of the facial color images.

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.

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

PubMed

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

2014-07-01

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

Macular Choroidal Thickness May Be the Earliest Determiner to Detect the Onset of Diabetic Retinopathy in Patients with Prediabetes: A Prospective and Comparative Study.

PubMed

Yazgan, Serpil; Arpaci, Dilek; Celik, Haci Ugur; Dogan, Mustafa; Isık, Irem

2017-07-01

To evaluate the macular and peripapillary choroidal thickness and retinal volume in prediabetes. This prospective comparative study included 53 patients with prediabetes and 53 age- and sex-matched healthy subjects. Only right eyes were selected. Choroidal thicknesses (CT) and retinal volume were measured by optical coherence tomography. Macular CT was measured at the seven points including macular center, 1, 2, and 3 mm distances along the temporal and nasal scans. Peripapillary CT was measured at the eight points of the optic disk area. Systemic and laboratory findings of the subjects were also recorded. There were no significant differences in blood pressures, ocular findings including intraocular pressure, visual acuity, and refractive powers, and macular volumes between the two groups (p > 0.005). Macular and peripapillary CT at all measuring points, body mass index (BMI), fasting blood glucose (FBG), hemoglobinA1C, and lipid profile were significantly higher in prediabetic patients (p < 0.05). There was a significant positive correlation between all points of macular choroidal thicknesses with BMI, FBG, and hemoglobin A1C (p < 0.05). Prediabetic factors including impaired FBG, increased hemoglobinA1C, and BMI are independent risk factors for increase in choroidal thickness. Increased macular choroidal thickness may be the earliest determiner to detect the onset of diabetic retinopathy in prediabetes.

Hematologic Profile and Semen Quality of Male Timor Deer (Rusa timorensis) at Various Hierarchies

NASA Astrophysics Data System (ADS)

Samsudewa, D.; Capitan, S. S.; Sevilla, C. C.; Vega, R. S. A.; Ocampo, P. P.

2018-02-01

The aim of this research was to observe hematologic profile i.e. erythrocyte count, hemoglobin and hematocrit and semen quality, i.e. semen volume, sperm motility and sperm abnormality of α-male, β-male and subordinate male Timor deer raised under captivity. Twelve males (51 ± 6 months old; 68.29 ± 8.41kg body weight) at similar antler stages were use in this study. Before and after 43 days of establishment of dominance hierarchy blood were sampled after sedation for erythrocyte count, hemoglobin (mg/dL), and hematocrit (%). Likewise, semen was collected using electroejaculator and were analyzed for semen volume (ml), sperm motility (%) and sperm abnormality (%) to compare male deer at various heirarchies. Wilcoxon signed ranks test and Kruskal-Wallis H test of non-parametric analysis was done. Significant difference was tested with Mann-Whitney U test. The results showed that highest count of erythrocyte shown on α and β-male (1.60 million per µL). The highest increase in hematocrit was observed in β-male (5%) and then followed by S2-male (4%). S2-male had the highest increase in hemoglobin (0.13 g/dL). The highest increase in semen volume was observed in α -male (0.75 ml). Social stress affected negatively the sperm motility and abnormality (P<0.05). The highest decrease was observed in S2-male.

Evaluation of the concomitant use of methotrexate and curcumin on Freund's complete adjuvant-induced arthritis and hematological indices in rats.

PubMed

Banji, David; Pinnapureddy, Jyothi; Banji, Otilia J F; Kumar, A Ranjith; Reddy, K Narsi

2011-09-01

To evaluate the concomitant administration of methotrexate and curcumin for antiarthiritic activity in rats. Arthritis was induced in rats following a single subplantar injection of Freund's complete adjuvant (0.1 ml). Rats were divided into six groups of six animals each. Group I and II were control injected with saline and Freund's complete adjuvant (0.1 ml), respectively. Group III arthritic rats were treated with curcumin (100 mg/kg, i.p.) on alternate days. Group IV received methotrexate (MTX) (2 mg/kg, i.p.) once in a week. Group-V and VI were treated with MTX (1 mg/kg, i.p.) once in a week and after 30 min received curcumin (30 mg/kg and 100 mg/kg, thrice a week, i.p.) from 10(th) to 45(th) days, respectively. Body weight and the paw volume was measured on 9(th), 16(th), 23(rd), 30(th), 37(th), and 45(th) days. Determination of complete blood cell counts, hemoglobin concentration, hematocrit, mean corpuscular volume, and mean corpuscular hemoglobin concentration was determined on the 46(th) day. An improvement in body weight and a significant (P < 0.05) reduction in arthritis was observed with the combination treatment as compared to the positive control. A significant improvement in the hematological profile was also observed in rats treated with curcumin and methotrexate. The study showed a significant anti-arthritic action and protection from hematological toxicity with the combination treatment of methotrexate and curcumin.

Feasibility of direct oxygenation of primary-cultured rat hepatocytes using polyethylene glycol-decorated liposome-encapsulated hemoglobin (LEH).

PubMed

Naruto, Hirosuke; Huang, Hongyun; Nishikawa, Masaki; Kojima, Nobuhiko; Mizuno, Atsushi; Ohta, Katsuji; Sakai, Yasuyuki

2007-10-01

We tested the short-term efficacy of liposome-encapsulated hemoglobin (LEH) in cultured rat hepatocytes. Supplementation with LEH (20% of the hemoglobin concentration of blood) did not lower albumin production in static culture, and completely reversed the cell death and deterioration in albumin production caused by an oxygen shortage in 2D flat-plate perfusion bioreactors.

Truncated hemoglobins in actinorhizal nodules of Datisca glomerata.

PubMed

Pawlowski, K; Jacobsen, K R; Alloisio, N; Ford Denison, R; Klein, M; Tjepkema, J D; Winzer, T; Sirrenberg, A; Guan, C; Berry, A M

2007-11-01

Three types of hemoglobins exist in higher plants, symbiotic, non-symbiotic, and truncated hemoglobins. Symbiotic (class II) hemoglobins play a role in oxygen supply to intracellular nitrogen-fixing symbionts in legume root nodules, and in one case ( Parasponia Sp.), a non-symbiotic (class I) hemoglobin has been recruited for this function. Here we report the induction of a host gene, dgtrHB1, encoding a truncated hemoglobin in Frankia-induced nodules of the actinorhizal plant Datisca glomerata. Induction takes place specifically in cells infected by the microsymbiont, prior to the onset of bacterial nitrogen fixation. A bacterial gene (Frankia trHBO) encoding a truncated hemoglobin with O (2)-binding kinetics suitable for the facilitation of O (2) diffusion ( ) is also expressed in symbiosis. Nodule oximetry confirms the presence of a molecule that binds oxygen reversibly in D. glomerata nodules, but indicates a low overall hemoglobin concentration suggesting a local function. Frankia trHbO is likely to be responsible for this activity. The function of the D. glomerata truncated hemoglobin is unknown; a possible role in nitric oxide detoxification is suggested.

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

PubMed

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

2015-12-01

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

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.

Chemical Immobilization of Sloth Bears (Melursus ursinus) with Ketamine Hydrochloride and Xylazine Hydrochloride: Hematology and Serum Biochemical Values

PubMed Central

Veeraselvam, M.; Sridhar, R.; Perumal, P.; Jayathangaraj, M. G.

2014-01-01

The present study was conducted to define the physiological responses of captive sloth bears immobilized with ketamine hydrochloride and xylazine hydrochloride and to determine and compare the values of hematology and serum biochemical parameters between sexes. A total of 15 sloth bears were immobilized using combination of ketamine hydrochloride and xylazine hydrochloride drugs at the dose rate of 5.0 milligram (mg) per kg body weight and 2.0 mg per kg body weight, respectively. The use of combination of these drugs was found satisfactory for the chemical immobilization of captive sloth bears. There were no significant differences observed in induction time and recovery time and physiological parameters such as heart rate, respiratory rate, and rectal temperature between sexes. Health related parameters comprising hematological values like packed cell volume (PCV), hemoglobin (Hb), red blood cell count (RBC), erythrocyte indices, and so forth and biochemical values like total protein, blood urea nitrogen (BUN), creatinine, alkaline amino-transferase (ALT), aspartate amino-transferase (AST), and so forth were estimated in 11 (5 males and 6 females) apparently healthy bears. Comparison between sexes revealed significant difference in PCV (P < 0.05) and mean corpuscular hemoglobin concentration (MCHC) (P < 0.05). The study might help to evaluate health profiles of sloth bears for appropriate line treatment. PMID:24876990

[Pernicious anemia: diagnosis and course in Burkina Faso].

PubMed

Koulidiati, J; Sawadogo, S; Sagna, Y; Somda, K S; Tieno, H; Kafando, E; Drabo, Y J

2015-01-01

Pernicious anemia (also known as Biermer disease or anemia, Addison or Addisonian anemia, and Addison-Biermer anemia) is an autoimmune atrophic gastritis responsible for vitamin B12 malabsorption due to a deficiency of intrinsic factor. We report eight cases of pernicious anemia in Burkina Faso, collected over a 44-month period. The three criteria for diagnosis of pernicious anemia were: vitamin B12 deficiency, gastric disease (gastric histology) with presence of anti-intrinsic factor, and/or anti-gastric parietal cell antibodies in serum. All patients had anemia, with a mean hemoglobin level of 8.75 g/100 mL. The average mean corpuscular volume (MCV) was 122.1 fL the average mean corpuscular hemoglobin (MCH) 39.3 pg, the mean reticulocyte count 12.069 10(9)/L reticulocytes, and the mean rate of megaloblast marrow cells 17.2%. The serum vitamin B12 level ranged from 35 to 71 pmol/L. Antibodies against intrinsic factor were found in all eight patients. All ABO blood groups were present with a predominance (4 cases) of group O. Endoscopy found a normal fundic mucosa in three patients. Histology showed gastric atrophy and intestinal metaplasia for six patients (85.7%). Under B12 vitamin therapy, the course was favorable in all patients; seven patients also had 10 days of iron therapy. We recommend a gastric biopsy even in the absence of macroscopic gastric lesions on the upper gastrointestinal endoscopy.

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

PubMed

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

2014-01-23

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

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

Gray wolf density and its association with weights and hematology of pups from 1970 to 1988

USGS Publications Warehouse

DelGiudice, Glenn D.; Mech, L. David; Seal, U.S.

1991-01-01

We examined weights and hematologic profiles of gray wolf (Canis lupus) pups and the associated wolf density in the east-central Superior National Forest of northeastern Minnesota (USA) during 1970 to 1988. We collected weight and hematologic data from 117 pups (57 females, 60 males) during 1 September to 22 November each year. The wolf density (wolves/800 km2) trend was divided into three phases: high (72 ± 7), 1970 to 1975; medium (44 ± 2), 1976 to 1983; and low (27 ± 2), 1984 to 1988. Wolf numbers declined (P = 0.0001) 39 and 63% from 1970 to 1975 to 1976 to 1983 and from 1970 to 1975 to 1984 to 1988, respectively. Weight was similar between male and female pups and did not vary as wolf density changed. Mean hemoglobin (P = 0.04), red (P = 0.0001) and white blood cells (P = 0.002), mean corpuscular volume, mean corpuscular hemoglobin concentration and mean corpuscular hemoglobin (P = 0.0001) did differ among the multi-annual phases of changing wolf density. Weight and hematologic data also were compared to values from captive wolf pups. The high, but declining wolf density was associated with macrocytic, normochromic anemia in wolf pups, whereas the lowest density coincided with a hypochromic anemia. Although hematologic values show promise for assessing wolf pup condition and wolf population status, they must be used cautiously until data are available from other populations.

Novel optical oxy/deoxy hemoglobin monitoring as a modality for non-invasive real-time monitoring of cognitive activity and beyond

NASA Astrophysics Data System (ADS)

Davies-Shaw, Dana; Huser, Thomas R.

2008-02-01

We report on the successful development of a custom in vitro system that provides a physiologically relevant means of demonstrating optical methodologies for the calibration and validation of oxygen delivery and hemoglobin oxygen binding dynamics in the brain. While measured optical signals have generally been equated to heme absorbance values that are, in turn, presumed to correspond to oxygen delivery, there has been little specific study of the sigmoidal oxygen binding dynamics of hemoglobin, a tetrameric protein, within physiologically relevant parameters. Our development of this novel analytical device addresses this issue, and is a significant step towards the minimally invasive and real-time monitoring of spatially resolved cognitive processes. As such, it is of particular interest for the detection of autistic brain activity in infants and young children. Moreover, our device and approach bring with them the ability to quantify and spatially resolve oxygen delivery down to volumes relevant to individual cell oxygen uptake, without any oxygen consumption, and with a temporal resolution that is physically unachievable by any oxygen tracking modality such as fMRI etc. Such a capability opens up myriad possibilities for further investigation, such as real-time tumor biopsy and resection; the tracking and quantification of cellular proliferation, as well as metabolic measures of tissue viability, to name but a few. Our system has also been engineered to be synergistic with virtually all imaging techniques, optical and otherwise.

Rapid rather than gradual weight reduction impairs hemorheological parameters of Taekwondo athletes through reduction in RBC-NOS activation.

PubMed

Yang, Woo Hwi; Heine, Oliver; Pauly, Sebastian; Kim, Pilsang; Bloch, Wilhelm; Mester, Joachim; Grau, Marijke

2015-01-01

Rapid weight reduction is part of the pre-competition routine and has been shown to negatively affect psychological and physiological performance of Taekwondo (TKD) athletes. This is caused by a reduction of the body water and an electrolyte imbalance. So far, it is unknown whether weight reduction also affects hemorheological properties and hemorheology-influencing nitric oxide (NO) signaling, important for oxygen supply to the muscles and organs. For this purpose, ten male TKD athletes reduced their body weight by 5% within four days (rapid weight reduction, RWR). After a recovery phase, athletes reduced body weight by 5% within four weeks (gradual weight reduction, GWR). Each intervention was preceded by two baseline measurements and followed by a simulated competition. Basal blood parameters (red blood cell (RBC) count, hemoglobin concentration, hematocrit, mean corpuscular volume, mean cellular hemoglobin and mean cellular hemoglobin concentration), RBC-NO synthase activation, RBC nitrite as marker for NO synthesis, RBC deformability and aggregation parameters were determined on a total of eight investigation days. Basal blood parameters were not affected by the two interventions. In contrast to GWR, RWR decreased activation of RBC-NO synthase, RBC nitrite, respective NO concentration and RBC deformability. Additionally, RWR increased RBC aggregation and disaggregation threshold. The results point out that a rapid weight reduction negatively affects hemorheological parameters and NO signaling in RBC which might limit performance capacity. Thus, GWR should be preferred to achieve the desired weight prior to a competition to avoid these negative effects.

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

Hematologic and plasma chemistry values in captive psittacine birds.

PubMed

Polo, F J; Peinado, V I; Viscor, G; Palomeque, J

1998-01-01

Reference values for some hematologic parameters in 19 species and plasma chemical values in 11 species of Psittacine birds, including cockatoos, parrots, amazons, macaws, conures, and lories, were established for use in veterinary medicine. The following parameters were studied: hematocrit, hemoglobin concentration, erythrocyte number, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, erythrocyte dimensions, leukocyte number and differential leukocyte count, glucose, urea, uric acid, cholesterol, triglycerides, creatinine, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, creatinine phosphokinase, lactic dehydrogenase, gamma glutamyl transpeptidase, total plasma protein, albumin, globulins, albumin-globulin ratio, sodium, potassium, calcium, magnesium, total phosphorus, chloride, and osmolality. Hematologically, the Psittacine is a very homogeneous avian group, with small differences between species. They are, however, different from other groups of birds.

Clinical Utility of Multimodality Imaging with Dynamic Contrast-Enhanced MRI, Diffusion-Weighted MRI, and 18F-FDG PET/CT for the Prediction of Neck Control in Oropharyngeal or Hypopharyngeal Squamous Cell Carcinoma Treated with Chemoradiation

PubMed Central

Chan, Sheng-Chieh; Lin, Yu-Chun; Yen, Tzu-Chen; Liao, Chun-Ta; Chang, Joseph Tung-Chieh; Ko, Sheung-Fat; Wang, Hung- Ming; Chang, Chee-Jen; Wang, Jiun-Jie

2014-01-01

The clinical usefulness of pretreatment imaging techniques for predicting neck control in patients with oropharyngeal or hypopharyngeal squamous cell carcinoma (OHSCC) treated with chemoradiation remains unclear. In this prospective study, we investigated the role of pretreatment dynamic contrast-enhanced perfusion MR imaging (DCE-PWI), diffusion-weighted MR imaging (DWI), and [18F]fluorodeoxyglucose-positron emission tomography (18F-FDG PET)/CT derived imaging markers for the prediction of neck control in OHSCC patients treated with chemoradiation. Patients with untreated OHSCC scheduled for chemoradiation between August, 2010 and July, 2012 were eligible for the study. Clinical variables and the following imaging parameters of metastatic neck lymph nodes were examined in relation to neck control: transfer constant, volume of blood plasma, and volume of extracellular extravascular space (Ve) on DCE-PWI; apparent diffusion coefficient (ADC) on DWI; maximum standardized uptake value, metabolic tumor volume, and total lesion glycolysis on 18F-FDG PET/CT. There were 69 patients (37 with oropharynx SCC and 32 with hypopharynx SCC) with successful pretreatment DCE-PWI and DWI available for analysis. After a median follow-up of 31 months, 25 (36.2%) participants had neck failure. Multivariate analysis identified hemoglobin level <14.3 g/dL (P = 0.019), Ve <0.23 (P = 0.040), and ADC >1.14×10−3 mm2/s (P = 0.003) as independent prognostic factors for 3-year neck control. A prognostic scoring system was formulated by summing up the three significant predictors of neck control. Patients with scores of 2–3 had significantly poorer neck control and overall survival rates than patients with scores of 0–1. We conclude that hemoglobin levels, Ve, and ADC are independent pretreatment prognostic factors for neck control in OHSCC treated with chemoradiation. Their combination may identify a subgroup of patients at high risk of developing neck failure. PMID:25531391

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.

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.

Analysis of Retinal Thinning Using Spectral-domain Optical Coherence Tomography Imaging of Sickle Cell Retinopathy Eyes Compared to Age- and Race-Matched Control Eyes.

PubMed

Lim, Jennifer I; Cao, Dingcai

2018-03-17

To determine whether the retina is thinner in sickle cell patients than in race- and age-matched controls, and, if it is thinner, whether there is any association with systemic diseases. Sickle cell and control (age- and race-matched) patients were prospectively enrolled from a university retina clinic into this observational study. Participants underwent visual acuity testing, slit-lamp biomicroscopy, dilated ophthalmoscopy, and spectral-domain optical coherence tomography imaging. Sickle cell retinal lesions, degree of vascular tortuosity, caliber of arteriovenous anastomosis, and stage of retinopathy were noted. Early Treatment Diabetic Retinopathy Study (ETDRS) subfield measurements were compared between sickle cell and control subjects and also among sickle cell hemoglobin subtypes. Associations between ETDRS subfield measurements and hemoglobin subtype, retinopathy stage, and systemic diseases were assessed. A total of 513 sickle cell eyes (260 patients) and 75 control eyes (39 patients) had median visual acuities of 20/20. ETDRS central (P = .002), inner (nasal P = .009, superior P = .021, temporal P < .001, inferior P = .017), and temporal outer (P = .012) subfield measurements were thinner in sickle cell eyes compared to control eyes. Hemoglobin SS eyes had significantly thinner inner ETDRS subfield measurements compared to SC and SThal eyes. Retinal thinning in all subfields was associated with age (P = .017) for sickle cell and control eyes. No association was found between retinal thinning and hydroxyurea use or arteriovenous anastomosis caliber. The macula is thinner in sickle cell eyes compared to control eyes; retinal thickness decreases with increasing age and sickle cell retinopathy stage and is most severe in hemoglobin SS subtypes. Copyright © 2018 Elsevier Inc. All rights reserved.

Effect of chronic altitude hypoxia on hematologic and glycolytic parameters.

PubMed

Clench, J; Ferrell, R E; Schull, W J

1982-05-01

The physiological effect of chronic exposure to altitude hypoxia on the glycolytic intermediates, adenosine triphosphate and 2,3-diphosphoglyceric acid, and the hematologic parameters, hemoglobin, hematocrit, and mean cell hemoglobin concentration, has been examined in an indigenous population, the Aymara, of the Departamento de Arica, Chile. This population normally resides at three altitudes: the coast (0-500 m), the sierra (2,500-3,500 m), and the altiplano (above 4,200 m). After isolation of altitude from other environmental factors (age, sex, body build, ethnicity, smoking, and residential permanence), an increase in 2,3-diphosphoglycerate and a decrease in adenosine triphosphate was observed. Both hemoglobin and hematocrit increased as expected, but mean cell hemoglobin concentration declined. It is proposed that a decline in the activity of a single enzyme, pyruvate kinase, can account for these observed changes and suggests a pivotal role for pyruvate kinase in the physiological adaptation to altitude hypoxia.

Design Modification of Electrophoretic Equipment

NASA Technical Reports Server (NTRS)

Reddick, J. M.; Hirsch, I.

1973-01-01

The improved design of a zone electrophoretic sampler is reported that can be used in mass screening for hemoglobin S, the cause of sickle cell anemia. Considered is a high voltage multicell cellulose acetate device that requires 5 to 6 minutes electrophoresis periods; cells may be activitated individually or simultaneously. A multisample hemoglobin applicator standardizes the amount of sample applied and transfers the homolysate to the electrical wires.

Noninvasive monitoring of cerebral oxygenation in preterm infants: preliminary observations.

PubMed

Brazy, J E; Lewis, D V; Mitnick, M H; Jöbsis vander Vliet, F F

1985-02-01

A noninvasive optical method for bedside monitoring of cerebral oxygenation in small preterm infants was evaluated. Through differential absorbance of near infrared light, changes in the oxidation-reduction level of cytochrome aa3, in the oxygenation state of hemoglobin and in tissue blood volume were assessed in the transilluminated anterior cerebral field. Overall, cerebral oxygenated hemoglobin correlated significantly with transcutaneous oxygen, r = .44 p less than .0001; however, correlation was best in the absence of cardiorespiratory disease. Hypoxia with or without bradycardia led to hemoglobin deoxygenation and a shift in cytochrome aa3 to a more reduced state. When hypoxic episodes came in series or were prolonged, aa3 reduction occurred simultaneous with hemoglobin deoxygenation but its recovery to base-line values sometimes lagged behind the return of hemoglobin oxygenation. In one infant with a large patent ductus arteriosus, even brief episodes of mild bradycardia caused precipitous reduction of cytochrome aa3 before any shift to greater hemoglobin deoxygenation. This response disappeared after ductal ligation. In general, the antecedent state of cerebral oxygenation, the severity and duration of deoxygenation, and the presence or absence of circulatory abnormalities all influenced the aa3 response to hypoxia. Continuous noninvasive near infrared monitoring of cerebral oxygenation can be performed on sick preterm infants at the bedside.

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

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

Prevalence of anaemia in pregnant women during the last trimester: consequense for birth weight.

PubMed

Demmouche, A; Lazrag, A; Moulessehoul, S

2011-04-01

Iron deficiency continues to be one of the most prevalent single-nutrient deficiencies in the world. The current study aimed to estimate the prevalence of iron deficiency anemia (IDA) among pregnant women who attend Antenatal Care Centers in Sidi Bel Abbes, Algeria. The effect of anaemia on infant birth weight was also examined. The study was conducted during the period March-Mai, 2010 and the sample consisted of 207 pregnant women (in the third trimesters) in the age group (17-41) years. The subjects were not taking iron, folate or vitamin B12 supplements at the time of the study. Blood samples were collected from each pregnant woman and a questionnaire was completed at the time of blood collection. A series of determinations was conducted to determine hemoglobin concentration (Hb); packed cell volume (PCV); corpuscular hemoglobin concentration (MCHC), corpuscular volume (MCV). The effect of anemia on the weight of new born babies was examined by calculating the correlation coefficient of birth weight and hematological indexes. The overall prevalence of anemia was found to be 46.86%. According to the severity anemia was 36.08% mild, 49.48% moderate and 14.43% severe anemia. The mean values (+/- SD) of haematological indexes were as follows: Hb 9.00 +/- 1.57 g/dl; PCV 27 +/- 5.37%; mean corpuscular haemoglobin concentration (MCHC) 33.75 +/- 2.69 g/dl and mean corpuscular volume (MCV) 75.7 +/- 10.4 fl. The results have shown that 46.39% of the subjects had MCV values less than standard value of 75 fl suggesting a microcytic anemia. The mean haemoglobin concentration was 9 +/- 1.57 g/dl while the mean birth weight was 3201.54 +/- 566.71 g. There was a not significant correlation between the Hb level and the birth weight of the infants (r = 0.28, p > 0.05). The prevalence of low birth weight was 9.2%. There was no statistically significant haemoglobin concentration /foetal birth weight difference among the various hemoglobin concentration (Chi square test = 0.34, p > 0.05). Anemia had no significant obstetric adverse effects in our pregnant population (Fischer test = 0.06, p > 0.05). There was no statistically significant difference in mean birth weight among the various haemoglobin groups suggesting that other parameters may play important roles in influencing the birth weight than the maternal haemoglobin concentration.

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

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.

Tissue lead distribution and hematologic effects in American kestrels (Falco sparverius) fed biologically incorporated lead

USGS Publications Warehouse

Custer, T.W.; Franson, J.C.; Pattee, O.H.

1984-01-01

American kestrels were fed a diet containing 0.5, 120, 212, and 448 ppm (dry wt) biologically incorporated lead (Pb) for 60 days. The diet consisted of homogenized 4-wk-old cockerels raised on feed mixed with and without lead. No kestrels died and weights did not differ among treatment groups. The control group (0.5 ppm Pb) had the lowest mean concentration of lead and the high dietary group had the highest for the following tissues: Kidney, liver, femur, brain, and blood. Concentrations of lead were significantly correlated among tissues. There were no differences among treatment groups for packed cell volume, hemoglobin concentration, or erythrocyte count.

Rapid increase in red blood cell density driven by K:Cl cotransport in a subset of sickle cell anemia reticulocytes and discocytes.

PubMed

Fabry, M E; Romero, J R; Buchanan, I D; Suzuka, S M; Stamatoyannopoulos, G; Nagel, R L; Canessa, M

1991-07-01

We have previously demonstrated that young normal (AA) and sickle cell anemia (SS) red blood cells are capable of a volume regulatory decrease response (VRD) driven by a K:Cl cotransporter that is activated by low pH or hypotonic conditions. We now report on the characteristics of young SS cells (SS2, discocytes) capable of rapid increase in density in response to swelling. We have isolated cells with high VRD response (H-VRD) and low VRD response (L-VRD) cells by incubation and density-gradient centrifugation under hypotonic conditions. Comparison of these cells in patients homozygous for hemoglobin (Hb)S indicated that H-VRD cells have 91% more reticulocytes (P less than 9 x 10(-9) than L-VRD cells, 25% less HbF (P less than 5.5 x 10(-5), 106% more NEM (N-methylmaleimide)-stimulated K:Cl cotransport activity (P less than 2 x 10(-4), and 86% more volume-stimulated K:Cl cotransport activity (P less than 1.8 x 10(-3). H-VRD and L-VRD cells have similar G-6-PD and Na+/H+ antiport activity. In agreement with the reduced percent HbF in H-VRD cells, F cells (red blood cells that contain fetal Hb) are depleted from the H-VRD population; however, F reticulocytes are enriched in the H-VRD population to the same extent as non-F reticulocytes, which suggests that both F and non-F reticulocytes have a similar initial distribution of volume-sensitive K:Cl cotransport activity but that it may be more rapidly inactivated in F than in S reticulocytes. We find that H-VRD cells consist of 20% reticulocytes (or 79% of all reticulocytes in SS2) and 80% more mature cells. This study demonstrates the role of K:Cl cotransport in determining red blood cell density, the heterogeneity of K:Cl cotransport activity in reticulocytes, and the capacity for rapid change in the density of reticulocytes with high K:Cl cotransport activity. We speculate that the H-VRD population may be more susceptible to generation of dense and irreversibly sickled cells.

Isoproterenol attenuates high vascular pressure-induced permeability increases in isolated rat lungs.

PubMed

Parker, J C; Ivey, C L

1997-12-01

To separate the contributions of cellular and basement membrane components of the alveolar capillary barrier to the increased microvascular permeability induced by high pulmonary venous pressures (Ppv), we subjected isolated rat lungs to increases in Ppv, which increased capillary filtration coefficient (Kfc) without significant hemorrhage (31 cmH2O) and with obvious extravasation of red blood cells (43 cmH2O). Isoproterenol (20 microM) was infused in one group (Iso) to identify a reversible cellular component of injury, and residual blood volumes were measured to assess extravasation of red blood cells through ruptured basement membranes. In untreated lungs (High Ppv group), Kfc increased 6.2 +/- 1.3 and 38.3 +/- 15.2 times baseline during the 31 and 43 cmH2O Ppv states. In Iso lungs, Kfc was 36.2% (P < 0.05) and 64.3% of that in the High Ppv group at these Ppv states. Residual blood volumes calculated from tissue hemoglobin contents were significantly increased by 53-66% in the high Ppv groups, compared with low vascular pressure controls, but there was no significant difference between High Ppv and Iso groups. Thus isoproterenol significantly attenuated vascular pressure-induced Kfc increases at moderate Ppv, possibly because of an endothelial effect, but it did not affect red cell extravasation at higher vascular pressures.

Nitric Oxide in Plants: The Roles of Ascorbate and Hemoglobin

PubMed Central

Wang, Xiaoguang; Hargrove, Mark S.

2013-01-01

Ascorbic acid and hemoglobins have been linked to nitric oxide metabolism in plants. It has been hypothesized that ascorbic acid directly reduces plant hemoglobin in support of NO scavenging, producing nitrate and monodehydroascorbate. In this scenario, monodehydroascorbate reductase uses NADH to reduce monodehydroascorbate back to ascorbate to sustain the cycle. To test this hypothesis, rates of rice nonsymbiotic hemoglobin reduction by ascorbate were measured directly, in the presence and absence of purified rice monodehydroascorbate reductase and NADH. Solution NO scavenging was also measured methodically in the presence and absence of rice nonsymbiotic hemoglobin and monodehydroascorbate reductase, under hypoxic and normoxic conditions, in an effort to gauge the likelihood of these proteins affecting NO metabolism in plant tissues. Our results indicate that ascorbic acid slowly reduces rice nonsymbiotic hemoglobin at a rate identical to myoglobin reduction. The product of the reaction is monodehydroascorbate, which can be efficiently reduced back to ascorbate in the presence of monodehydroascorbate reductase and NADH. However, our NO scavenging results suggest that the direct reduction of plant hemoglobin by ascorbic acid is unlikely to serve as a significant factor in NO metabolism, even in the presence of monodehydroascorbate reductase. Finally, the possibility that the direct reaction of nitrite/nitrous acid and ascorbic acid produces NO was measured at various pH values mimicking hypoxic plant cells. Our results suggest that this reaction is a likely source of NO as the plant cell pH drops below 7, and as nitrite concentrations rise to mM levels during hypoxia. PMID:24376554

Regulation of Hemoglobin β-Chain Synthesis in Bone Marrow Erythroid Cells by α Chains

PubMed Central

Wolf, Jeffrey L.; Mason, R. George; Honig, George R.

1973-01-01

Synthesis of α and β chains of hemoglobin was studied in vitro in intact reticulocytes and bone marrow cells. The cells were from rabbits having a variant form of hemoglobin in which L-isoleucine is in the α but not in the β chains. This characteristic permitted a selective inhibition of α-chain synthesis to be produced by addition to the incubation medium of L-O-methylthreonine, an inhibitor of protein synthesis that is a specific antagonist of L-isoleucine. In studies with reticulocytes, 25 mM L-O-methylthreonine produced a 60-70% inhibition of α-chain synthesis, but β-chain synthesis was unaffected even after incubation times for 4 hr. Because reticulocytes contain a pool of uncombined α chains which might have obscured the demonstration of an α chain-dependent mechanism for β-chain synthesis, subsequent studies were done with bone marrow cells. The latter had little or no detectable α-chain pool. A substantial inhibition of α-chain synthesis by the bone marrow cells was produced by the isoleucine antagonist but was also accompanied by a significantly decreased rate of β-chain synthesis. These findings suggest that the coordinated synthesis of the complementary α- and β-globin chains of hemoglobin may reflect in part a modifying effect of α-chain synthesis on the synthesis of β chains. PMID:4519634

Pulsed-dosing with oral sodium phenylbutyrate increases hemoglobin F in a patient with sickle cell anemia.

PubMed

Hines, Patrick; Dover, George J; Resar, Linda M S

2008-02-01

Increasing hemoglobin F (HbF) appears to be beneficial for patients with sickle cell anemia. We previously demonstrated that daily, oral sodium phenylbutyrate (OSPB) induces HbF synthesis in pediatric and adult patients with hemoglobin SS (HbSS). The high doses and need for daily therapy, however, have limited its use. Here, we report a patient treated with pulsed-dosing of OSPB for over 3 years. This patient developed a modest, but sustained elevation in HbF over the course of therapy without side effects. Although larger studies are needed, this case demonstrates that pulsed-dosing with OSPB enhances HbF synthesis. (c) 2007 Wiley-Liss, Inc.

Comparative study of sickle cell anemia and hemoglobin SC disease: clinical characterization, laboratory biomarkers and genetic profiles.

PubMed

Aleluia, Milena Magalhães; Fonseca, Teresa Cristina Cardoso; Souza, Regiana Quinto; Neves, Fábia Idalina; da Guarda, Caroline Conceição; Santiago, Rayra Pereira; Cunha, Bruna Laís Almeida; Figueiredo, Camylla Villas Boas; Santana, Sânzio Silva; da Paz, Silvana Sousa; Ferreira, Júnia Raquel Dutra; Cerqueira, Bruno Antônio Veloso; Gonçalves, Marilda de Souza

2017-01-01

In this study, we evaluate the association of different clinical profiles, laboratory and genetic biomarkers in patients with sickle cell anemia (SCA) and hemoglobin SC disease (HbSC) in attempt to characterize the sickle cell disease (SCD) genotypes. We conducted a cross-sectional study from 2013 to 2014 in 200 SCD individuals (141 with SCA; 59 with HbSC) and analyzed demographic data to characterize the study population. In addition, we determined the association of hematological, biochemical and genetic markers including the β S -globin gene haplotypes and the 3.7 Kb deletion of α-thalassemia (-α 3.7Kb -thal), as well as the occurrence of clinical events in both SCD genotypes. Laboratory parameters showed a hemolytic profile associated with endothelial dysfunction in SCA individuals; however, the HbSC genotype was more associated with increased blood viscosity and inflammatory conditions. The BEN haplotype was the most frequently observed and was associated with elevated fetal hemoglobin (HbF) and low S hemoglobin (HbS). The -α 3.7Kb -thal prevalence was 0.09 (9%), and it was associated with elevated hemoglobin and hematocrit concentrations. Clinical events were more frequent in SCA patients. Our data emphasize the differences between SCA and HbSC patients based on laboratory parameters and the clinical and genetic profile of both genotypes.

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

NASA Astrophysics Data System (ADS)

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

2017-02-01

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

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

PubMed

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

2012-01-01

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

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.

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

Photon dynamics in tissue imaging

NASA Astrophysics Data System (ADS)

Chance, Britton; Haselgrove, John C.; Wang, NaiGuang; Maris, Michael B.; Sevick-Muraca, Eva M.

1991-11-01

The emerging need for a fast, safe economical approach to global and localized measures of desaturation of hemoglobin with oxygen (HbO2) in the human brain motivates further research on time-resolved spectroscopy in four areas of study. (1) To afford quantization of hemoglobin saturation through time-resolved spectroscopy in the time domain (TD) and in the frequency domain (FD). Evaluation of dual-wavelength TD and FD spectrometers for determining quantitatively hemoglobin desaturation and blood-volume changes by calculations that are insensitive to mutual interference is proposed. The diffusion equation, as it applies especially to TD studies, and the absorption ((mu) a) and scattering ((mu) s) coefficients provide their independent determination from the late and early respective portions of the kinetics of the emergent photons in response to a short input pulse (50-100 psec). (2) The identification of the photon-pathlength change due to the arterial pulse in the brain tissue by FD methods with Fourier transformation affords an opportunity to employ principles of pulse oximetry to vessels localized deep within the brain tissue. (3) Localization of desaturation of hemoglobin in portions of the brain can be achieved through dual-wavelength scanning of the input/output optical fibers across the head for an X-Y coordinate and varying the distance between input and output ((rho) ) or the time delay in data acquisition to afford an in-depth Z scan. Localizations of shed blood, which have an effective concentration of over 10 times that of capillary-bed blood, are identified by X, Y, Z scans using only a single wavelength. (4) Independent measurements of absorption ((mu) a) and scattering ((mu) s) coefficients, particularly by TD techniques, affords structural mapping of the brain, which can be used to diagnose brain tumor and neuronal degeneration. Two experimental systems are used to critically evaluate these studies; the first, a hemoglobin/lipid/yeast model in which intermittent oxygenation gives saturation/desaturation effects and addition of hemoglobin simulates increased blood volume. These models can be global or may contain localized ''black'' absorbers simulating brain bleeds or model-stroke volumes in which oxygenation/deoxygenation simulates normoxia/hypoxia. Secondly, animal brains are used to model the following changes in vivo: global or localized hypoxia, brain bleeding, and hematomas by epidural blood injection, and physiological changes by epilepsy. Neuronal degeneration causing scattering effects is modeled by injection, epidurally or into the animal model brain, highly scattering material such as polystyrene spheres. The proposal envisages a basic science study of photon migration in the brain with important applications to stroke, epilepsy, brain trauma, and neuronal degenerative disease.

Comparison of Spectra Optia and COBE Spectra apheresis systems' performances for red blood cell exchange procedures.

PubMed

Kim, Jaehyup; Joseph, Ranjit; Matevosyan, Karen; Sarode, Ravi

2016-12-01

Spectra Optia (Terumo BCT, Lakewood, CO) was FDA approved for red blood cell exchange (RBCx) procedures in January 2014 and is expected to replace COBE spectra (Terumo BCT) very soon in the USA. The performance characteristics of these devices for Isovolemic Hemodilution (IHD-RBCx) procedure were compared in this study. A total of 114 IHD-RBCx procedures from 19 patients were analyzed. For every patient, three procedures on each device with similar pre-procedure hematocrits were compared. Pre and post procedure laboratory parameters compared were hemoglobin S (HbS), hematocrits (Hct), platelet counts and fraction of cells remaining (FCR). Statistical analysis was performed using t-test adjusted by the Holm-Bonferroni method to reduce family-wise error rate. There were no significant differences between these two devices in regards to HbS, Hct, FCR and platelet counts (p = > 0.05). However, rinseback volume (124.2 ± 8.9 ml) and normal saline replacement volume during IHD phase (296.1 ± 97.2 ml) were lower in Spectra Optia as compared to COBE Spectra (337 ± 33.8 ml and 326.6 ± 105.2 ml, p value <0.001 and 0.030 respectively). Spectra Optia had a longer run time (107.1 ± 15.9 min vs 123.8 ± 19.6 min, p value <0.001) overall. Performance characteristics of Spectra Optia for HbS, Hct and FCR were similar to COBE Spectra for IHD-RBCx. IHD-RBCx procedure on Optia required less normal saline replacement volume and rinse back volume but with overall longer procedure run time. Copyright © 2016. Published by Elsevier Ltd.

Photolyses of mammalian carboxy-hemoglobin studied by photoacoustic calorimetry

NASA Astrophysics Data System (ADS)

Zhao, JinYu; Li, JiaHuang; Zhang, Zheng; Zhang, ShuYi; Qu, Min; Fang, JianWen; Hua, ZiChun

2013-07-01

The enthalpy and conformational volume changes in the photolyses of carboxy-hemoglobin (HbCO) of human, bovine, pig, horse and rabbit are investigated by photoacoustic calorimetry. Considering the time scales of the exciting laser pulse and the receiving ultrasound transducers (PVDF films and PZT ceramics), as well as the reaction lifetimes in the photolysis processes of HbCO, the measured results are related to the geminate recombination and tertiary relaxation in photolyses of HbCO. Moreover, the quantum yields of the five mammals are also measured by laser pump-probe technique. The results show that the dynamic parameters, such as enthalpy and conformational volume changes, differ between the processes of the geminate recombination and tertiary relaxation. Also, the dynamic parameters differ among the five mammals although some of them may be consistent with each other.

Blood mononuclear cell gene expression profiles characterize the oxidant, hemolytic, and inflammatory stress of sickle cell disease

PubMed Central

Jison, Maria L.; Munson, Peter J.; Barb, Jennifer J.; Suffredini, Anthony F.; Talwar, Shefali; Logun, Carolea; Raghavachari, Nalini; Beigel, John H.; Shelhamer, James H.; Danner, Robert L.; Gladwin, Mark T.

2016-01-01

In sickle cell disease, deoxygenation of intra-erythrocytic hemoglobin S leads to hemoglobin polymerization, erythrocyte rigidity, hemolysis, and microvascular occlusion. Ischemia-reperfusion injury, plasma hemoglobin-mediated nitric oxide consumption, and free radical generation activate systemic inflammatory responses. To characterize the role of circulating leukocytes in sickle cell pathogenesis we performed global transcriptional analysis of blood mononuclear cells from 27 patients in steady-state sickle cell disease (10 patients treated and 17 patients untreated with hydroxyurea) compared with 13 control subjects. We used gender-specific gene expression to validate human microarray experiments. Patients with sickle cell disease demonstrated differential gene expression of 112 genes involved in heme metabolism, cell-cycle regulation, antioxidant and stress responses, inflammation, and angiogenesis. Inducible heme oxygenase-1 and downstream proteins biliverdin reductase and p21, a cyclin-dependent kinase, were up-regulated, potentially contributing to phenotypic heterogeneity and absence of atherosclerosis in patients with sickle cell disease despite endothelial dysfunction and vascular inflammation. Hydroxyurea therapy did not significantly affect leukocyte gene expression, suggesting that such therapy has limited direct anti-inflammatory activity beyond leukoreduction. Global transcriptional analysis of circulating leukocytes highlights the intense oxidant and inflammatory nature of steady-state sickle cell disease and provides insight into the broad compensatory responses to vascular injury. PMID:15031206

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

PubMed

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

2015-04-01

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

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.

Sex-specific reference intervals of hematologic and biochemical analytes in Sprague-Dawley rats using the nonparametric rank percentile method.

PubMed

He, Qili; Su, Guoming; Liu, Keliang; Zhang, Fangcheng; Jiang, Yong; Gao, Jun; Liu, Lida; Jiang, Zhongren; Jin, Minwu; Xie, Huiping

2017-01-01

Hematologic and biochemical analytes of Sprague-Dawley rats are commonly used to determine effects that were induced by treatment and to evaluate organ dysfunction in toxicological safety assessments, but reference intervals have not been well established for these analytes. Reference intervals as presently defined for these analytes in Sprague-Dawley rats have not used internationally recommended statistical method nor stratified by sex. Thus, we aimed to establish sex-specific reference intervals for hematologic and biochemical parameters in Sprague-Dawley rats according to Clinical and Laboratory Standards Institute C28-A3 and American Society for Veterinary Clinical Pathology guideline. Hematology and biochemistry blood samples were collected from 500 healthy Sprague-Dawley rats (250 males and 250 females) in the control groups. We measured 24 hematologic analytes with the Sysmex XT-2100i analyzer, 9 biochemical analytes with the Olympus AU400 analyzer. We then determined statistically relevant sex partitions and calculated reference intervals, including corresponding 90% confidence intervals, using nonparametric rank percentile method. We observed that most hematologic and biochemical analytes of Sprague-Dawley rats were significantly influenced by sex. Males had higher hemoglobin, hematocrit, red blood cell count, red cell distribution width, mean corpuscular volume, mean corpuscular hemoglobin, white blood cell count, neutrophils, lymphocytes, monocytes, percentage of neutrophils, percentage of monocytes, alanine aminotransferase, aspartate aminotransferase, and triglycerides compared to females. Females had higher mean corpuscular hemoglobin concentration, plateletcrit, platelet count, eosinophils, percentage of lymphocytes, percentage of eosinophils, creatinine, glucose, total cholesterol and urea compared to males. Sex partition was required for most hematologic and biochemical analytes in Sprague-Dawley rats. We established sex-specific reference intervals, including corresponding 90% confidence intervals, for Sprague-Dawley rats. Understanding the significant discrepancies in hematologic and biochemical analytes between male and female Sprague-Dawley rats provides important insight into physiological effects in test rats. Establishment of locally sex-specific reference intervals allows a more precise evaluation of animal quality and experimental results of Sprague-Dawley rats in our toxicology safety assessment.

The influence of moderate-intensity physical effort on peripheral blood in adults with Down syndrome - a pilot study.

PubMed

Aleksander-Szymanowicz, P; Marchewka, A; Dabrowski, Z; Teleglow, A; Bac, A; Glodzik, J

2014-10-01

The aim of this study was to evaluate the influence of a six-week aerobic training on peripheral blood in adults with Down syndrome. Fifteen men with Down syndrome (average age 22.4 years ± 0.91) with moderate or severe intellectual disability took part in the study. Patients underwent a training program three times a week for six weeks. Venous blood samples of 10 ml were collected from every examined patient, 24 hours before and after the exercise. The blood samples were submitted to hematological examination (hematocrit, fibrinogen, plasma viscosity, red blood cell (RBC) number, RBC indicators: mean corpuscular volume (MCV), mean corpuscular hemoglobin concentration (MCHC), mean corpuscular hemoglobin (MCH)), reduced glutathione (GSH) level and number of macrocytes, polikilocytrometric examination of RBC and rheological blood examination (elongation index (EI), aggregation index (AI), syllectogram amplitude (AMP), aggregation half time (t1/2)) was made by LORCA. Amoderate six-week physical training performed on a cycloergometer resulted in a statistically significant decrease in the MCV value, hematocrit and plasma viscosity. The six-week cycloergometer training caused a statistically significant increase in the GSH level and erythrocyte pliability at a shear stress of 0.58 Pa.

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.

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.

Effects of Khaya senegalensis leaves on performance, carcass traits, hemtological and biochemical parameters in rabbits

PubMed Central

Abdel-Wareth, A. A. A.; Hammad, Seddik; Ahmed, Hassan

2014-01-01

One of the challenges facing farmers today is to ensure adequate integration of natural resources into animal feeds. The aim of the present study is to evaluate the effects of Khaya senegalensis (KS) leaves on the performance of growing male rabbits, carcass traits and biochemical as well as hematological parameters. Thirty New Zealand White male growing rabbits were randomly divided into 3 groups (10 rabbits per group). Group I (control) received standard rabbit diet. Rabbits in group II and group III were fed standard rabbit diet supplemented with 35 % and 65 % KS leaves, respectively. All rabbits were fed daily for 25 days. The performance parameters and carcass criteria, including daily body weight gain, final body weight, and the percentage of dressing, were increased in rabbits fed 35 % KS when compared to the control group. Kidney and liver weight ratios increased significantly in group II but dropped in group III. Furthermore, liver enzymes - alanine aminotransferase and aspartate transaminase and kidney function parameters - urea, and creatinine - increased in both group II (significant P<0.05) and in group III (significant P<0.01) when compared to the control group. Moreover, KS leaves induced a significant increase (P<0.05) in the total white blood cell count, the percentage of granulocytes and the platelet count; whereas, the percentage of lymphocytes, red blood cell count, hemoglobin content, mean corpuscular hemoglobin, mean corpuscular volume and mean corpuscular hemoglobin concentration were not statistically significantly changed. This study demonstrates that the performance parameters and carcass traits are improved by the replacement of rabbit's diet with KS leaves. However, KS leaves may adversely affect liver and kidney function in a dose-dependent manner. Therefore, further studies are required to elucidate the maximum tolerable and toxic, as well as lethal doses, and to isolate the pharmacologically active components from KS leaves. PMID:26417277

Response and adaptation of Beagle dogs to hypergravity

NASA Technical Reports Server (NTRS)

Oyama, J.

1975-01-01

Eight male Beagle dogs, five months old, were centrifuged continuously for three months at progressively increasing loads. Heart rate and deep body temperature were monitored continuously by implant biotelemetry. Initially, centrifuged dogs showed transient decreases in heart rate and body temperature along with changes in their diurnal rhythm patterns. Compared with normal gravity controls, exposed dogs showed a slower growth rate and a reduced amount of body fat. Blood protein, total lipids, cholesterol, calcium, packed cell volume, red blood cell count, and hemoglobin were also decreased significantly. Absolute weights of the leg bones of centrifuged dogs were significantly greater than controls. Photon absorptiometry revealed significant density increases in selective regions of the femur and humerus of centrifuged dogs. In spite of the various changes noted, results from this and other studies affirm the view that dogs can tolerate and adapt to sustained loads as high as 2.5 g without serious impairment of their body structure and function.

Sickle cell anemia and mitral valve replacement. Case report.

PubMed

Bomfim, V; Ribeiro, A; Gouvea, F; Pereira, J; Björk, V

1989-01-01

An 8-year-old black boy with sickle cell disease and severe hemolytic anemia crisis (95% hemoglobin S) also had mitral incompetence due to rheumatic valve disease. A 27 mm monostrut Björk-Shiley valve prosthesis was implanted after partial exchange transfusions had reduced the hemoglobin S to less than 40%. High-flow normothermic perfusion was used during extracorporeal circulation, with care taken to avoid hypoxia and acidosis. Postoperative recovery was uneventful.

[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.

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.

Analytical performance evaluation of a high-volume hematology laboratory utilizing sigma metrics as standard of excellence.

PubMed

Shaikh, M S; Moiz, B

2016-04-01

Around two-thirds of important clinical decisions about the management of patients are based on laboratory test results. Clinical laboratories are required to adopt quality control (QC) measures to ensure provision of accurate and precise results. Six sigma is a statistical tool, which provides opportunity to assess performance at the highest level of excellence. The purpose of this study was to assess performance of our hematological parameters on sigma scale in order to identify gaps and hence areas of improvement in patient care. Twelve analytes included in the study were hemoglobin (Hb), hematocrit (Hct), red blood cell count (RBC), mean corpuscular volume (MCV), red cell distribution width (RDW), total leukocyte count (TLC) with percentages of neutrophils (Neutr%) and lymphocytes (Lymph %), platelet count (Plt), mean platelet volume (MPV), prothrombin time (PT), and fibrinogen (Fbg). Internal quality control data and external quality assurance survey results were utilized for the calculation of sigma metrics for each analyte. Acceptable sigma value of ≥3 was obtained for the majority of the analytes included in the analysis. MCV, Plt, and Fbg achieved value of <3 for level 1 (low abnormal) control. PT performed poorly on both level 1 and 2 controls with sigma value of <3. Despite acceptable conventional QC tools, application of sigma metrics can identify analytical deficits and hence prospects for the improvement in clinical laboratories. © 2016 John Wiley & Sons Ltd.

Microvascular oxygen consumption during sickle cell pain crisis.

PubMed

Rowley, Carol A; Ikeda, Allison K; Seidel, Miles; Anaebere, Tiffany C; Antalek, Matthew D; Seamon, Catherine; Conrey, Anna K; Mendelsohn, Laurel; Nichols, James; Gorbach, Alexander M; Kato, Gregory J; Ackerman, Hans

2014-05-15

Sickle cell disease is an inherited blood disorder characterized by chronic hemolytic anemia and episodic vaso-occlusive pain crises. Vaso-occlusion occurs when deoxygenated hemoglobin S polymerizes and erythrocytes sickle and adhere in the microvasculature, a process dependent on the concentration of hemoglobin S and the rate of deoxygenation, among other factors. We measured oxygen consumption in the thenar eminence during brachial artery occlusion in sickle cell patients and healthy individuals. Microvascular oxygen consumption was greater in sickle cell patients than in healthy individuals (median [interquartile range]; sickle cell: 0.91 [0.75-1.07] vs healthy: 0.75 [0.62-0.94] -ΔHbO2/min, P < .05) and was elevated further during acute pain crisis (crisis: 1.10 [0.78-1.30] vs recovered: 0.88 [0.76-1.03] -ΔHbO2/min, P < .05). Increased microvascular oxygen consumption during pain crisis could affect the local oxygen saturation of hemoglobin when oxygen delivery is limiting. Identifying the mechanisms of elevated oxygen consumption during pain crisis might lead to the development of new therapeutic interventions. This trial was registered at www.clinicaltrials.gov as #NCT01568710.

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.

Mild splenic sequestration crises in sickle-hemoglobin C disease.

PubMed

Andrews, J; Buchanan, G R

1984-06-01

Acute splenic sequestration crisis ( ASSC ), a common complication in homozygous sickle cell anemia, has been described infrequently in sickle-hemoglobin C (SC) disease in the absence of high altitude exposure. In this report, we describe three children with hemoglobin SC disease who developed episodes of ASSC that were milder than those generally described in sickle cell anemia. In one patient, an antecedent triggering event was not recognized. The other two children may have had a predisposing cause for massive intrasplenic sickling in that one had an associated mononucleosis syndrome and the other an episode of hypovolemic shock following severe epistaxis. ASSC may occur in patients with SC disease and does not necessarily require a hypoxic trigger associated with high altitudes.

Synergistic effects of intravenous and intra-articular tranexamic acid on reducing hemoglobin loss in revision total knee arthroplasty: a prospective, randomized, controlled study.

PubMed

Yuan, Xiangwei; Wang, Jiaxing; Wang, Qiaojie; Zhang, Xianlong

2018-04-01

Tranexamic acid decreases blood loss in primary total knee arthroplasty, and no related prospective randomized clinical trials have been conducted to evaluate the effectiveness and safety of tranexamic acid in revision total knee arthroplasty. Thus, we conducted this work to evaluate the synergistic effects of intravenous plus intra-articular tranexamic acid on reducing hemoglobin loss compared with intra-articular tranexamic acid alone in revision total knee arthroplasty. This prospective, controlled study randomized 96 patients undergoing revision total knee arthroplasty into two groups: an intravenous plus intra-articular tranexamic acid group (48 patients who received 20 mg/kg intravenous tranexamic acid and 3.0 g intra-articular tranexamic acid); and an intra-articular tranexamic acid alone group (48 patients who received the same intravenous volume of normal saline and 3.0 g intra-articular tranexamic acid). The primary outcome was hemoglobin loss. Secondary outcomes included the volume of drain output, the percentage of patients who received transfusions, the number of units transfused, and thromboembolic events. The baseline data, preoperative hemoglobin, and tourniquet time were similar in both groups. There was significantly less hemoglobin loss in the intravenous plus intra-articular tranexamic acid group compared with the intra-articular tranexamic acid alone group (2.7 ± 0.6 g/dL and 3.7 ± 0.7 g/dL; p < 0.001). Compared with the intra-articular tranexamic acid alone group, the intravenous plus intra-articular tranexamic acid group also had significantly less drain output, fewer patients who received transfusions, and fewer units transfused (all p < 0.05). There were no significant differences in thromboembolic events in the two groups during the 3-month follow-up. Compared with intra-articular tranexamic acid alone, combined intravenous plus intra-articular tranexamic acid significantly reduced hemoglobin loss and the need for transfusion without an apparent increase in thromboembolic events in patients who underwent revision total knee arthroplasty. © 2018 AABB.

Dhatrilauha: Right choice for iron deficiency anemia in pregnancy.

PubMed

Roy, Anuradha; Dwivedi, Manjari

2014-01-01

Anemia in pregnancy is multi-factorial. Iron deficiency anemia (IDA) is the most common one. Major cause is increased demand of iron during pregnancy. In Ayurveda, under Pandu-Roga the features of anemia are described. It is characterized by Vaivarnyata or Varnanasha (change/destruction in normal color of the body), a disorder of Pitta vitiation. Ayurvedic management is an effective way of curing anemia in general by a large number of Lauha preparations of which Dhatrilauha has been used widely for centuries. To evaluate the effect of Dhatrilauha in the management of IDA based on the scientific parameters among pregnant patients. A total of 58 cases were selected by simple randomized sampling method as per inclusion criteria of pregnant women between 4(th) and 7(th) months of pregnancy with a clinical diagnosis and laboratory confirmation of IDA. Dhatrilauha 500 mg in two divided doses after food with normal potable water were given for 45 days with three follow-ups, each of 15 days intervals. Final assessment was done after completion of 45 days and results were statistically analyzed by using Cochran's Q-test and Student's t-test. Dhatrilauha showed statistically significant (P < 0.01) improvement in the majority of sign-symptoms and objective parameters such as weakness, fatigue, palpitation, effort intolerance, breathlessness, heartburn, pallor, constipation, hemoglobin, red blood cells (RBC), hematocrit, mean corpuscular volume, mean corpuscular hemoglobin concentration, RBC distribution width, mean platelet volume, serum iron, and total iron binding capacity. Dhatrilauha possesses many fold effectiveness in anemia (IDA), which was evidenced with the significant results obtained in the majority of parameters in this study.

A relay network of extracellular heme-binding proteins drives C. albicans iron acquisition from hemoglobin.

PubMed

Kuznets, Galit; Vigonsky, Elena; Weissman, Ziva; Lalli, Daniela; Gildor, Tsvia; Kauffman, Sarah J; Turano, Paola; Becker, Jeffrey; Lewinson, Oded; Kornitzer, Daniel

2014-10-01

Iron scavenging constitutes a crucial challenge for survival of pathogenic microorganisms in the iron-poor host environment. Candida albicans, like many microbial pathogens, is able to utilize iron from hemoglobin, the largest iron pool in the host's body. Rbt5 is an extracellular glycosylphosphatidylinositol (GPI)-anchored heme-binding protein of the CFEM family that facilitates heme-iron uptake by an unknown mechanism. Here, we characterize an additional C. albicans CFEM protein gene, PGA7, deletion of which elicits a more severe heme-iron utilization phenotype than deletion of RBT5. The virulence of the pga7-/- mutant is reduced in a mouse model of systemic infection, consistent with a requirement for heme-iron utilization for C. albicans pathogenicity. The Pga7 and Rbt5 proteins exhibit distinct cell wall attachment, and discrete localization within the cell envelope, with Rbt5 being more exposed than Pga7. Both proteins are shown here to efficiently extract heme from hemoglobin. Surprisingly, while Pga7 has a higher affinity for heme in vitro, we find that heme transfer can occur bi-directionally between Pga7 and Rbt5, supporting a model in which they cooperate in a heme-acquisition relay. Together, our data delineate the roles of Pga7 and Rbt5 in a cell surface protein network that transfers heme from extracellular hemoglobin to the endocytic pathway, and provide a paradigm for how receptors embedded in the cell wall matrix can mediate nutrient uptake across the fungal cell envelope.

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 different modes of using tranexamic acid administration on reducing hidden blood loss in total hip arthroplasty].

PubMed

Ni, Jin-Rong; Wang, Li-Xin; Chen, Xin-Jun

2016-08-25

To compare the clinical efficacy of using tranexamic acid in different ways to reduce the hidden blood loss in patients who receiving total hip arthroplasty (THA). Totally 68 patients with osteonecrosis of the femeral head treated by total hip arthroplasty in our hospital from February 2010 to July 2015 were randomly divided into the intravenous drip group (group A) and the topical application group (group B). In group A, there were 19 males and 15 females, with an average age of (62.0±6.4) years old, preoperative average hemoglobin was (121.30±8.15) g/L, average Hematocrit was (0.470±0.039) L/L. In group B, there were 18 males and 16 females, with an average age of (64.0±7.5) years old, preoperative average hemoglobin was (125.28±9.37) g/L, average Hematocrit was (0.490±0.041) L/L. The operation incision were performed through the posterolateral approach and the normal operation mode, biological prosthesis was selected. Through different ways the tranexamic acid was used to control of intraoperative and postoperative bleeding. Tranexamic acid was intra articular injection as a dose of 10 mg/kg 10 min to patient before anesthesia in intravenous drip group. In topic group, 3 g of tranexamic acid was dissolved in 120 ml saline and divided into three equal parts, then two pieces of gauze were immersed in 40 ml tranexamic acid solution. One gauze with 40 ml tranexamic acid was used to soak the acetabulum for 5 minutes after the acetabular preparation, another gauze was inserted in the femoral canal for 5 minutes after femoral canal broach preparation. The remaining 40 ml tranexamic acid fluid was injected into the hip joint after fascia closure. Place the drainage tube and clip it for 3 hours. Hemoglobin (Hb) and Hematocrit (Hct) were recorded at 72 hours after operation. The total blood loss, dominant blood loss, and hidden blood loss were calculated. In group A, postoperative hemoglobin difference before and after operation was (32.34±7.42) g/L, total blood loss was (833.6±81.4) ml, the hidden blood loss was (276.3±57.9) ml, red blood cell volume was (10.1±1.4) L/L;In group B, hemoglobin difference before and after operation was (28.2±6.1) g/L, total blood loss was (792.5±61.8) ml, the hidden blood loss was (297.5±50.3) ml, red blood cell volume was (9.2±1.2) L/L. There was no statistical significance about those aspect ( P >0.05). Compared of blood coagulation function between two groups, in group A: PT (12.78±2.03) s, APTT (34.27±3.91) s, INR (32.34±7.42); and in group B: PT (13.17±2.19) s, APTT (32.36±3.18) s, INR (28.24±6.14). There was no significant differences also ( P >0.05). Compared with intravenous application, topical application of tranexamic acid could also effectively reduce total blood loss and hidden blood loss, postoperative blood transfusion rate in primary total hip arthroplasty, while does not increase the risk of DVT.

Measurement of Human Blood and Plasma Volumes

NASA Technical Reports Server (NTRS)

Greenleaf, J. E.; Szalkay, H. G. H.

1987-01-01

Report reviews techniques for measuring blood-plasma volume in humans. Common technique of using radioactive iodine isotope to label plasma albumin involves unwarranted risks from low-level radiation. Report emphasizes techniques using Evans-blue-dye (T-1824) labeling of albumin, hematocrit or hemoglobin/hematocrit measurements, or blood densitometry. In Evans-blue-dye technique, plasma volume determined from decrease in dye concentration occurring after small amount of dye solution injected into circulatory system. Subjection of Evans blue dye to test for carcinogenicity gave negative results.

Ultrasonic processing for recovery of chicken erythrocyte hemoglobin

USDA-ARS?s Scientific Manuscript database

Hemoglobin from chicken blood has been shown to be a good substitute for synthetic polymeric flocculants. One stage of processing the blood entails breaking open the cells and releasing the cytoplasmic contents; in the present study, we investigate the use of ultrasonic processing at this stage. Was...

The effects of Spirulina on anemia and immune function in senior citizens

PubMed Central

Selmi, Carlo; Leung, Patrick SC; Fischer, Laura; German, Bruce; Yang, Chen-Yen; Kenny, Thomas P; Cysewski, Gerry R; Gershwin, M Eric

2011-01-01

Anemia and immunological dysfunction (i.e. immunosenescence) are commonly found in older subjects and nutritional approaches are sought to counteract these phenomena. Spirulina is a filamentous and multicellular bule-green alga capable of reducing inflammation and also manifesting antioxidant effects. We hypothesized that Spirulina may ameliorate anemia and immunosenescence in senior citizens with a history of anemia. We enrolled 40 volunteers of both sexes with an age of 50 years or older who had no history of major chronic diseases. Participants took a Spirulina supplementation for 12 weeks and were administered comprehensive dietary questionnaires to determine their nutritional regimen during the study. Complete cell count (CCC) and indoleamine 2,3-dioxygenase (IDO) enzyme activity, as a sign of immune function, were determined at baseline and weeks 6 and 12 of supplementation. Thirty study participants completed the entire study and the data obtained were analyzed. Over the 12-week study period, there was a steady increase in average values of mean corpuscular hemoglobin in subjects of both sexes. In addition, mean corpuscular volume and mean corpuscular hemoglobin concentration also increased in male participants. Older women appeared to benefit more rapidly from Spirulina supplements. Similarly, the majority of subjects manifested increased IDO activity and white blood cell count at 6 and 12 weeks of Spirulina supplementation. Spirulina may ameliorate anemia and immunosenescence in older subjects. We encourage large human studies to determine whether this safe supplement could prove beneficial in randomized clinical trials. PMID:21278762

The effects of Spirulina on anemia and immune function in senior citizens.

PubMed

Selmi, Carlo; Leung, Patrick S C; Fischer, Laura; German, Bruce; Yang, Chen-Yen; Kenny, Thomas P; Cysewski, Gerry R; Gershwin, M Eric

2011-05-01

Anemia and immunological dysfunction (i.e. immunosenescence) are commonly found in older subjects and nutritional approaches are sought to counteract these phenomena. Spirulina is a filamentous and multicellular bule-green alga capable of reducing inflammation and also manifesting antioxidant effects. We hypothesized that Spirulina may ameliorate anemia and immunosenescence in senior citizens with a history of anemia. We enrolled 40 volunteers of both sexes with an age of 50 years or older who had no history of major chronic diseases. Participants took a Spirulina supplementation for 12 weeks and were administered comprehensive dietary questionnaires to determine their nutritional regimen during the study. Complete cell count (CCC) and indoleamine 2,3-dioxygenase (IDO) enzyme activity, as a sign of immune function, were determined at baseline and weeks 6 and 12 of supplementation. Thirty study participants completed the entire study and the data obtained were analyzed. Over the 12-week study period, there was a steady increase in average values of mean corpuscular hemoglobin in subjects of both sexes. In addition, mean corpuscular volume and mean corpuscular hemoglobin concentration also increased in male participants. Older women appeared to benefit more rapidly from Spirulina supplements. Similarly, the majority of subjects manifested increased IDO activity and white blood cell count at 6 and 12 weeks of Spirulina supplementation. Spirulina may ameliorate anemia and immunosenescence in older subjects. We encourage large human studies to determine whether this safe supplement could prove beneficial in randomized clinical trials.

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.

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

Kidney epithelium specific deletion of kelch-like ECH-associated protein 1 (Keap1) causes hydronephrosis in mice.

PubMed

Noel, Sanjeev; Arend, Lois J; Bandapalle, Samatha; Reddy, Sekhar P; Rabb, Hamid

2016-08-02

Transcription factor Nrf2 protects from experimental acute kidney injury (AKI) and is promising to limit progression in human chronic kidney disease (CKD) by upregulating multiple antioxidant genes. We recently demonstrated that deletion of Keap1, the endogenous inhibitor of Nrf2, in T lymphocytes significantly protects from AKI. In this study, we investigated the effect of Keap1 deletion on Nrf2 mediated antioxidant response in the renal tubular epithelial cells. We deleted Keap1 exon 2 and 3 in the renal tubular epithelial cells by crossing Ksp-Cre mice with Keap1 floxed (Keap1 (f/f)) mice. Deletion of Keap1 gene in the kidney epithelial cells of Ksp-Keap1 (-/-) mice and its effect on Nrf2 target gene expression was performed using PCR and real-time PCR respectively. Histological evaluation was performed on H&E stained sections. Complete blood count, serum and urine analysis were performed to assess systemic effects of defective kidney development. Student's T test was used to determine statistical difference between the groups. Ksp-Cre resulted in the deletion of Keap1 exon 2 and 3 and subsequent upregulation of Nrf2 target genes, Nqo1, Gclm and Gclc in the kidney epithelial cells of Ksp-Keap1 (-/-) mice at baseline. Renal epithelial cell specific deletion of Keap1 in Ksp-Keap1 (-/-) mice caused marked renal pelvic expansion and significant compression of medullary parenchyma consistent with hydronephrosis in both (3 month-old) males and females. Kidneys from 6 month-old Ksp-Keap1 (-/-) mice showed progressive hydronephrosis. Hematological, biochemical and urinary analysis showed significantly higher red blood cell count (p = 0.04), hemoglobin (p = 0.01), hematocrit (p = 0.02), mean cell volume (p = 0.02) and mean cell hemoglobin concentration (p = 0.003) in Ksp-Keap1 (-/-) mice in comparison to Keap1 (f/f) mice. These unexpected findings demonstrate that Keap1 deletion in renal tubular epithelial cells results in an abnormal kidney development consistent with hydronephrosis and reveals a novel Keap1 mediated signaling pathway in renal development.

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

PubMed

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

2000-04-01

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

In vivo multispectral photoacoustic and photothermal flow cytometry with multicolor dyes: a potential for real-time assessment of circulation, dye-cell interaction, and blood volume

PubMed Central

Proskurnin, Mikhail A.; Zhidkova, Tatyana V.; Volkov, Dmitry S.; Sarimollaoglu, Mustafa; Galanzha, Ekaterina I.; Mock, Donald; Zharov, Vladimir P.

2011-01-01

Recently, photoacoustic (PA) flow cytometry (PAFC) has been developed for in vivo detection of circulating tumor cells and bacteria targeted by nanoparticles. Here, we propose multispectral PAFC with multiple dyes having distinctive absorption spectra as multicolor PA contrast agents. As a first step of our proof-of-concept, we characterized high-speed PAFC capability to monitor the clearance of three dyes (ICG, MB, and TB) in an animal model in vivo and in real time. We observed strong dynamic PA signal fluctuations, which can be associated with interactions of dyes with circulating blood cells and plasma proteins. PAFC demonstrated enumeration of circulating red and white blood cells labeled with ICG and MB, respectively, and detection of rare dead cells uptaking TB directly in bloodstream. The possibility for accurate measurements of various dye concentrations including CV and BG were verified in vitro using complementary to PAFC photothermal (PT) technique and spectrophotometry under batch and flow conditions. We further analyze the potential of integrated PAFC/PT spectroscopy with multiple dyes for rapid and accurate measurements of circulating blood volume without a priori information on hemoglobin content, which is impossible with existing optical techniques. This is important in many medical conditions including surgery and trauma with extensive blood loss, rapid fluid administration, transfusion of red blood cells. The potential for developing a robust clinical PAFC prototype that is, safe for human, and its applications for studying the liver function are further highlighted. PMID:21905207

Effects of regional hemoconcentration during LBNP on plasma volume determinations. [Lower Body Negative Pressure

NASA Technical Reports Server (NTRS)

Loeppky, J. A.; Kobayashi, Y.; Venters, M. D.; Luft, U. C.

1979-01-01

Blood samples were obtained from forearm vein or artery with indwelling cannula (1) before, (2) during the last min, and (3) about 2 min after lower body negative pressure (LBNP) in 16 experiments to determine whether plasma volume (PV) estimates were affected by regional hemoconcentration in the lower body. Total hemoglobin (THb) was estimated with the CO method prior to LBNP. Hemoglobin (Hb) and hematocrit (Hct) values from (2) gave only a 3% (87 ml) loss in PV due to LBNP, assuming no change in THb. However, Hb and Hct values from (3) showed an 11% loss in PV (313 ml). This 72% underestimation of PV loss with (2) must have resulted from the sequestration of blood and subsequent hemoconcentration in the lower body during LBNP. The effects of LBNP on PV should be estimated 1-3 min after exposure, after mixing but before extravascular fluid returns to the circulation.

Comparison of intravenous versus topical tranexamic acid in primary total hip and knee arthroplasty: An updated meta-analysis.

PubMed

Xie, Jinwei; Hu, Qinsheng; Huang, Qiang; Ma, Jun; Lei, Yiting; Pei, Fuxing

2017-05-01

The appropriate route for administering tranexamic acid in primary total hip (THA) and knee arthroplasty (TKA) remains controversial. The purpose of this meta-analysis was to compare the efficacy and safety of topical or intravenous tranexamic acid. PubMed, EMBASE, and the Cochrane Library databases were systematically searched for randomized controlled trials (RCTs) comparing topical and intravenous tranexamic acid following primary THA or TKA. Primary outcomes were transfusion frequency and maximum drop in hemoglobin. Other parameters included total blood loss (TBL), hidden blood loss, drainage volume, hemoglobin level on postoperative day 1 (POD 1), deep vein thrombosis (DVT), pulmonary embolism (PE), wound complications and other adverse events. Data were analyzed using Rev Man 5.2. A total of 18 RCTs involving TKA and 4 RCTs involving THA, corresponding to approximately 2260 patients, were included in the meta-analysis. No significant difference between topical and intravenous tranexamic acid was found in transfusion requirement (RR 1.14, 95%CI 0.87 to 1.50, p=0.35). The maximum drop in hemoglobin was significantly smaller in the intravenous group than in the topical group (MD 0.33g/dL, 95%CI 0.07 to 0.58, p=0.01); similar results were observed for the subset of studies involving THA (MD 0.49g/dL, 95%CI 0.28 to 0.70, p<0.001) and the subset involving TKA (MD 0.30g/dL, 95%CI 0.02 to 0.59, p=0.04). The topical and intravenous groups did not differ significantly in TBL, drainage volume, hemoglobin level on POD 1, DVT, PE, wound complications or other adverse events. The available evidence indicates similar transfusion requirements and safety for topical and intravenous tranexamic acid in THA and TKA. However, intravenous injection seems to be associated with a smaller maximum drop in hemoglobin. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effects of chronic dietary lead in American kestrels (Falco sparverius)

USGS Publications Warehouse

Franson, J. Christian; Sileo, Louis; Pattee, Oliver H.; Moore, John F.

1983-01-01

American kestrels were fed a diet containing 0, 10, or 50 ppm lead (Pb) powder for at least 5 mo. Blood delta-aminolevulinic acid dehydratase (ALAD) activity in birds receiving 50 ppm Pb was as low as 20% of controls but no significant effects were noted in packed cell volume (PCV) or hemoglobin concentration (Hb). Mean liver Pb residues in birds fed 50 ppm Pb were 1.3 and 2.4 ppm (dry wt) for males and females, respectively. Liver Pb residues in birds fed 10 ppm Pb were not significantly greater than controls. There was no significant correlation between blood ALAD activity and blood Pb concentration, no consistent histopathological lesions were noted, and body and organ weights were not affected.

A hypothesis of target cell formation in sickle cell disease.

PubMed

Wong, P

2016-08-01

A fraction of erythrocytes appear as target cells in stained blood smears in sickle cell disease, due to a inheritance of the hemoglobin variant Hb S, polymerizing upon deoxygenation. These cells appear in a three dimension as thin cups. A process of their formation in this disease is proposed based on a band 3-based mechanism of the erythrocyte shape control, able to explain the erythrocyte echinocytosis by glucose depletion. It indicates that their formation is due to a stomatocytogenic slow outward transport of the dibasic form of endogenous Pi with an H(+) by band 3, promoted by the decrease of the Donnan ratio, which decreases cell pH and volume, attributed by a decrease of cell KCl concentration by the higher efflux of K(+)Cl(-) cotransport and Ca(2+) activation of the Gardos channel. Its implications are briefly discussed with respect to target cells per se, target cell formation in other hemoglobinopathies, acquired and inherited disorders of the lipid metabolism and dehydrated hereditary stomatocytosis as well as a stomatocyte presence in a double heterozygote of Hb S and Hb C and of an involvement of the process of target cell formation in acanthocytosis in acquired and inherited disorders. Copyright © 2016 Elsevier Ltd. All rights reserved.

Hypoxic survival requires a 2-on-2 hemoglobin in a process involving nitric oxide

PubMed Central

Hemschemeier, Anja; Düner, Melis; Casero, David; Merchant, Sabeeha S.; Winkler, Martin; Happe, Thomas

2013-01-01

Hemoglobins are recognized today as a diverse family of proteins present in all kingdoms of life and performing multiple reactions beyond O2 chemistry. The physiological roles of most hemoglobins remain elusive. Here, we show that a 2-on-2 (“truncated”) hemoglobin, termed THB8, is required for hypoxic growth and the expression of anaerobic genes in Chlamydomonas reinhardtii. THB8 is 1 of 12 2-on-2 hemoglobins in this species. It belongs to a subclass within the 2-on-2 hemoglobin class I family whose members feature a remarkable variety of domain arrangements and lengths. Posttranscriptional silencing of the THB8 gene results in the mis-regulation of several genes and a growth defect under hypoxic conditions. The latter is intensified in the presence of an NO scavenger, which also impairs growth of wild-type cells. As recombinant THB8 furthermore reacts with NO, the results of this study indicate that THB8 is part of an NO-dependent signaling pathway. PMID:23754374

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.

Renal effects of multiple infusion of pyridoxalated-hemoglobin-polyoxyethylene conjugate (PHP) solution in dogs.

PubMed

Takahashi, T; Iwasaki, K; Malchesky, P S; Harasaki, H; Matsushita, M; Nosé, Y; Rolin, H; Hall, P M

1993-03-01

Pyridoxalated-hemoglobin-polyoxyethylene conjugate (PHP), which is made from out-dated human red blood cells by two major chemical modifications, namely pyridoxalation and conjugation with polyoxyethylene (POE), is currently under development as a physiological oxygen carrier. This study assessed the effects of PHP-88 solution, which contains 8% (wt/vol) each of hemoglobin (Hb) and maltose, on renal function when it was infused 3 times every other day into the intact circulation of 8 dogs (5 dogs for the PHP group and 3 for the control group; 20 ml/kg for the first infusion, and 10 ml/kg each for the second and third infusions, at the rate of 2.5 ml/h/kg). Serial determinations of glomerular filtration rate (GFR) and renal plasma flow (RPF) were carried out pre- and postinfusion for up to 3 months along with measurements of blood and urine analyses, urine output rate, fractional excretion of sodium (FES), and free water clearance (CH2O). The results showed that plasma colloid osmotic pressure (COP) elevated an average of 3.3 mm Hg (p = 0.0085), and GFR and RPF tended to increase by 13% (NS) and 38% (NS), respectively, immediately after the third infusion with PHP solution. Urine output rate increased during and after the infusion, and FES and CH2O also increased for 24 h after the infusion in both groups. Blood urea nitrogen, serum creatinine, and serum Na+ concentrations were not affected greatly by the infusions, but hematocrit was decreased by 8% in the PHP group, indicating approximately a 42% expansion of plasma volume. These changes were observed to return to their preinfusion levels by 1 week postinfusion. Renal histology of the PHP group obtained at 2 weeks postinfusion revealed vacuole formation in the proximal tubules which was not associated with any pathologic changes indicative of cell death or regeneration. In 4 out of 5 dogs at 3 months postinfusion (necropsy), the vacuoles were not present. Though urinary N-acetyl-beta-glucosaminidase (NAG) activity had significantly increased after infusion, it returned to the preinfusion level by 1 month postinfusion. No detrimental effect of vacuoles on the assessed renal tubular functions was confirmed in the present study. The results demonstrated that multiple infusions of PHP solutions were well tolerated in normal dogs, and the observed effects were conceived predominantly attributable to the physiological response of the kidneys to an oncotic load into the circulation, which produced plasma volume expansion.

[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.

Skeletal Muscle Metrics on Clinical 18F-FDG PET/CT Predict Health Outcomes in Patients with Sarcoma

PubMed Central

Foster, Brent; Boutin, Robert D.; Lenchik, Leon; Gedeon, David; Liu, Yu; Nittur, Vinay; Badawi, Ramsey D.; Li, Chin-Shang; Canter, Robert J.; Chaudhari, Abhijit J.

2018-01-01

The aim of this study was to determine the association of measures of skeletal muscle determined from 18F-FDG PET/CT with health outcomes in patients with soft-tissue sarcoma. 14 patients (8 women and 6 men; mean age 66.5 years) with sarcoma had PET/CT examinations. On CTs of the abdomen and pelvis, skeletal muscle was segmented, and cross-sectional muscle area, muscle volume, and muscle attenuation were determined. Within the segmented muscle, intramuscular fat area, volume, and density were derived. On PET images, the standardized uptake value (SUV) of muscle was determined. Regression analyses were conducted to determine the association between the imaging measures and health outcomes including overall survival (OS), local recurrence-free survival (LRFS), distant cancer recurrence (DCR), and major surgical complications (MSC). The association between imaging metrics and pre-therapy levels of serum C-reactive protein (CRP), creatinine, hemoglobin, and albumin was determined. Decreased volumetric muscle CT attenuation was associated with increased DCR. Increased PET SUV of muscle was associated with decreased OS and LRFS. Lower muscle SUV was associated with lower serum hemoglobin and albumin. Muscle measurements obtained on routine 18F-FDG PET/CT are associated with outcomes and serum hemoglobin and albumin in patients with sarcoma. PMID:29756042

Skeletal Muscle Metrics on Clinical 18F-FDG PET/CT Predict Health Outcomes in Patients with Sarcoma.

PubMed

Foster, Brent; Boutin, Robert D; Lenchik, Leon; Gedeon, David; Liu, Yu; Nittur, Vinay; Badawi, Ramsey D; Li, Chin-Shang; Canter, Robert J; Chaudhari, Abhijit J

2018-01-01

The aim of this study was to determine the association of measures of skeletal muscle determined from 18 F-FDG PET/CT with health outcomes in patients with soft-tissue sarcoma. 14 patients (8 women and 6 men; mean age 66.5 years) with sarcoma had PET/CT examinations. On CTs of the abdomen and pelvis, skeletal muscle was segmented, and cross-sectional muscle area, muscle volume, and muscle attenuation were determined. Within the segmented muscle, intramuscular fat area, volume, and density were derived. On PET images, the standardized uptake value (SUV) of muscle was determined. Regression analyses were conducted to determine the association between the imaging measures and health outcomes including overall survival (OS), local recurrence-free survival (LRFS), distant cancer recurrence (DCR), and major surgical complications (MSC). The association between imaging metrics and pre-therapy levels of serum C-reactive protein (CRP), creatinine, hemoglobin, and albumin was determined. Decreased volumetric muscle CT attenuation was associated with increased DCR. Increased PET SUV of muscle was associated with decreased OS and LRFS. Lower muscle SUV was associated with lower serum hemoglobin and albumin. Muscle measurements obtained on routine 18 F-FDG PET/CT are associated with outcomes and serum hemoglobin and albumin in patients with sarcoma.

Evaluating dynamic contrast-enhanced and photoacoustic CT to assess intra-tumor heterogeneity in xenograft mouse models

NASA Astrophysics Data System (ADS)

Stantz, Keith M.; Liu, Bo; Cao, Minsong; Reinecke, Dan; Dzemidzic, Mario; Liang, Yun; Kruger, Robert

2006-03-01

Purpose: To evaluate photoacoustic CT spectroscopy (PCT-S) and dynamic contrast-enhanced CT (DCE-CT) ability to measure parameters - oxygen saturation and vascular physiology - associated with the intra-tumor oxygenation status. Material and Methods: Breast (VEGF165 enhance MCF-7) and ovarian (SKOV3x) cancer cells were implanted into the fat pads and flanks of immune deficient mice and allowed to grow to a diameter of 8-15 mm. CT was used to determine physiological parameters by acquiring a sequence of scans over a 10 minute period after an i.v. injection of a radio-opaque contrast agent (Isovue). These time-dependent contrast-enhanced curves were fit to a two-compartmental model determining tumor perfusion, fractional plasma volume, permeability-surface area produce, and fractional interstitial volume on a voxel-by-voxel basis. After which, the tumors were imaged using photoacoustic CT (Optosonics, Inc., Indianapolis, IN 46202). The near infrared spectra (700-910 nm) within the vasculature was fit to linear combination of measured oxy- and deoxy-hemoglobin blood samples to obtain oxygen saturation levels (SaO II). Results: The PCT-S scanner was first calibrated using different samples of oxygenated blood, from which a statistical error ranging from 2.5-6.5% was measured and a plot of the hemoglobin dissociation curve was consistent with empirical formula. In vivo determination of tumor vasculature SaO II levels were measurably tracked, and spatially correlated to the periphery of the tumor. Tumor depend variations in SaO II - 0.32 (ovarian) and 0.60 (breast) - and in vascular physiology - perfusion, 1.03 and 0.063 mL/min/mL, and fractional plasma volume, 0.20 and 0.07 - were observed. Conclusion: Combined, PCT-S and CED-CT has the potential to measure intra-tumor levels of tumor oxygen saturation and vascular physiology, key parameters associated with hypoxia.

Heme iron uptake by Caco-2 cells is a saturable, temperature sensitive and modulated by extracellular pH and potassium.

PubMed

Arredondo, Miguel; Kloosterman, Janneke; Núñez, Sergio; Segovia, Fabián; Candia, Valeria; Flores, Sebastián; Le Blanc, Solange; Olivares, Manuel; Pizarro, Fernando

2008-11-01

It is known that heme iron and inorganic iron are absorbed differently. Heme iron is found in the diet mainly in the form of hemoglobin and myoglobin. The mechanism of iron absorption remains uncertain. This study focused on the heme iron uptake by Caco-2 cells from a hemoglobin digest and its response to different iron concentrations. We studied the intracellular Fe concentration and the effect of time, K+ depletion, and cytosol acidification on apical uptake and transepithelial transport in cells incubated with different heme Fe concentrations. Cells incubated with hemoglobin-digest showed a lower intracellular Fe concentration than cells grown with inorganic Fe. However, uptake and transepithelial transport of Fe was higher in cells incubated with heme Fe. Heme Fe uptake had a low Vmax and Km as compared to inorganic Fe uptake and did not compete with non-heme Fe uptake. Heme Fe uptake was inhibited in cells exposed to K+ depletion or cytosol acidification. Heme oxygenase 1 expression increased and DMT1 expression decreased with higher heme Fe concentrations in the media. The uptake of heme iron is a saturable and temperature-dependent process and, therefore, could occur through a mechanism involving both a receptor and the endocytic pathway.

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.

Mapping Polymerization and Allostery of Hemoglobin S Using Point Mutations

PubMed Central

Weinkam, Patrick; Sali, Andrej

2014-01-01

Hemoglobin is a complex system that undergoes conformational changes in response to oxygen, allosteric effectors, mutations, and environmental changes. Here, we study allostery and polymerization of hemoglobin and its variants by application of two previously described methods: (i) AllosMod for simulating allostery dynamics given two allosterically related input structures and (ii) a machine-learning method for dynamics- and structure-based prediction of the mutation impact on allostery (Weinkam et al. J. Mol. Biol. 2013), now applicable to systems with multiple coupled binding sites such as hemoglobin. First, we predict the relative stabilities of substates and microstates of hemoglobin, which are determined primarily by entropy within our model. Next, we predict the impact of 866 annotated mutations on hemoglobin’s oxygen binding equilibrium. We then discuss a subset of 30 mutations that occur in the presence of the sickle cell mutation and whose effects on polymerization have been measured. Seven of these HbS mutations occur in three predicted druggable binding pockets that might be exploited to directly inhibit polymerization; one of these binding pockets is not apparent in the crystal structure but only in structures generated by AllosMod. For the 30 mutations, we predict that mutation-induced conformational changes within a single tetramer tend not to significantly impact polymerization; instead, these mutations more likely impact polymerization by directly perturbing a polymerization interface. Finally, our analysis of allostery allows us to hypothesize why hemoglobin evolved to have multiple subunits and a persistent low frequency sickle cell mutation. PMID:23957820

Exploring the Cytotoxic Potential of Triterpenoids-enriched Fraction of Bacopa monnieri by Implementing In vitro, In vivo, and In silico Approaches.

PubMed

Mallick, Md Nasar; Khan, Washim; Parveen, Rabea; Ahmad, Sayeed; Sadaf; Najm, Mohammad Zeeshan; Ahmad, Istaq; Husain, Syed Akhtar

2017-10-01

Bacopa monnieri (BM) is a herbaceous plant traditionally used from time immemorial in Ayurvedic and folklore medicines. We hypothesized that the extract of the whole plant might contain numerous molecules with having antitumor activities that could be very effective in killing of human cancer cells. This work investigated anticancer activity of bioactive fraction of BM. The hydroalcoholic extract of BM was fractionated with different solvent, namely, hexane, dichloromethane (DCM), acetone, methanol, and water. The in vitro anticancer activity was performed against various Human Cancer Cell lines, namely, Colon (HT29, Colo320, and Caco2), Lung (A549), Cervix (HeLa, SiHa), and Breast (MCF-7, MDAMB-231). Further, DCM fraction was evaluated in vivo for anticancer activity against Ehrlich ascites carcinoma (EAC) tumor-bearing mice since it showed the best cytotoxicity at 72 h (IC 50 41.0-60.0 µg/mL). The metabolic fingerprinting of these extract were carried out using high-performance thin-layer chromatography along with quantification of bacoside A, bacoside B, cucurbitacin B, cucurbitacin E, and bittulinic acid. Oral administration of DCM fraction at a dose of 40 mg/kg rendered prominent reduction of tumor regression parameters such as tumor weight, packed cell volume, tumor volume and viable tumor cell count as compared to the untreated mice of the EAC control group. The anticancer activity of DCM fraction may be due to the presence of large amount of bacoside A, B and cucurbitacins. The molecular docking studies of major metabolites with targeted proteins predicted the anticancer activity of DCM fraction which was in support of in vivo activity. The in vitro , in vivo , analytical and in silico studies on DCM fraction of Bacopa monieri has proved its great potential for development of anticancer phytopharmaceuticals. A new HPTLC method has been developed and validated for the qualitative and quantitative analysis of bacoside A, B, cucurbitacin B, D, E and bittulinic acid in Bacopa monnieri extract. Enrichment of active anticancer metabolites was done by polarity based fractionations of hydroalcoholic extract of Bacopa. DCM fraction of a hydroalcoholic extract of Bacopa showed anticancer potential against human cancer cell line (IC50 41.0-60.0 µg/mL) and in EAC treated mice (at a dose of 40 mg/kg body weight). The anticancer activity of Bacopa may be due to the presence of bacosides and cucurbitacin and it was confirmed by in silico screening. Abbreviations used: DBM: DCM fraction of Bacopa monnieri; DCM: Dichloromethane; EAC: Ehrlich ascites carcinoma; HCT: Hematocrit; HGB: Hemoglobin; HPTLC: High performance thin layer chromatography; ICH: International council for Harmonisation; LOD: Limit of detection; LOQ: Limit of quantification; LYM: Lymphocytes; MCH: Mean corpuscular hemoglobin; MCHC: Mean corpuscular haemoglobin concentration (MCHC); MCV: Mean corpuscular volume; MTT: 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; PLT: Platelet; RBC: Red blood cell; RDW: Red blood cell distribution width; RSD: Relative standard deviation; WBC: White blood cells.

Exploring the Cytotoxic Potential of Triterpenoids-enriched Fraction of Bacopa monnieri by Implementing In vitro, In vivo, and In silico Approaches

PubMed Central

Mallick, Md. Nasar; Khan, Washim; Parveen, Rabea; Ahmad, Sayeed; Sadaf; Najm, Mohammad Zeeshan; Ahmad, Istaq; Husain, Syed Akhtar

2017-01-01

Background: Bacopa monnieri (BM) is a herbaceous plant traditionally used from time immemorial in Ayurvedic and folklore medicines. We hypothesized that the extract of the whole plant might contain numerous molecules with having antitumor activities that could be very effective in killing of human cancer cells. Objectives: This work investigated anticancer activity of bioactive fraction of BM. Materials and Methods: The hydroalcoholic extract of BM was fractionated with different solvent, namely, hexane, dichloromethane (DCM), acetone, methanol, and water. The in vitro anticancer activity was performed against various Human Cancer Cell lines, namely, Colon (HT29, Colo320, and Caco2), Lung (A549), Cervix (HeLa, SiHa), and Breast (MCF-7, MDAMB-231). Further, DCM fraction was evaluated in vivo for anticancer activity against Ehrlich ascites carcinoma (EAC) tumor-bearing mice since it showed the best cytotoxicity at 72 h (IC50 41.0–60.0 µg/mL). The metabolic fingerprinting of these extract were carried out using high-performance thin-layer chromatography along with quantification of bacoside A, bacoside B, cucurbitacin B, cucurbitacin E, and bittulinic acid. Results: Oral administration of DCM fraction at a dose of 40 mg/kg rendered prominent reduction of tumor regression parameters such as tumor weight, packed cell volume, tumor volume and viable tumor cell count as compared to the untreated mice of the EAC control group. The anticancer activity of DCM fraction may be due to the presence of large amount of bacoside A, B and cucurbitacins. The molecular docking studies of major metabolites with targeted proteins predicted the anticancer activity of DCM fraction which was in support of in vivo activity. Conclusion: The in vitro, in vivo, analytical and in silico studies on DCM fraction of Bacopa monieri has proved its great potential for development of anticancer phytopharmaceuticals. SUMMARY A new HPTLC method has been developed and validated for the qualitative and quantitative analysis of bacoside A, B, cucurbitacin B, D, E and bittulinic acid in Bacopa monnieri extract. Enrichment of active anticancer metabolites was done by polarity based fractionations of hydroalcoholic extract of Bacopa. DCM fraction of a hydroalcoholic extract of Bacopa showed anticancer potential against human cancer cell line (IC50 41.0-60.0 µg/mL) and in EAC treated mice (at a dose of 40 mg/kg body weight). The anticancer activity of Bacopa may be due to the presence of bacosides and cucurbitacin and it was confirmed by in silico screening. Abbreviations used: DBM: DCM fraction of Bacopa monnieri; DCM: Dichloromethane; EAC: Ehrlich ascites carcinoma; HCT: Hematocrit; HGB: Hemoglobin; HPTLC: High performance thin layer chromatography; ICH: International council for Harmonisation; LOD: Limit of detection; LOQ: Limit of quantification; LYM: Lymphocytes; MCH: Mean corpuscular hemoglobin; MCHC: Mean corpuscular haemoglobin concentration (MCHC); MCV: Mean corpuscular volume; MTT: 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; PLT: Platelet; RBC: Red blood cell; RDW: Red blood cell distribution width; RSD: Relative standard deviation; WBC: White blood cells. PMID:29142420

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

Kapp, O.H.; Mainwaring, M.G.; Vinogradov, S.N.

A fraction of the extracellular hemoglobin of Lumbricus terrestris, obtained by gel filtration at neutral pH subsequent to dissociation either at pH 9.8 or at pH 4.0 or at pH 7.0 in 10 mM sodium phosphotungstate, consisting of the three subunits D1 (31 kDa), D2 (37 kDa) and T (50 kDa), produced two peaks when subjected to FPLC on a Superose 6 column at neutral pH. Peak I, eluting at a slightly greater volume than the native hemoglobin, consisted of reassociated hexagonal bilayer structures when examined by scanning transmission electron microscopy. The dimensions of the three reassociated hexagonal bilayer structuresmore » were 25 nm x 16 nm. Although the latter are smaller than the dimensions of the native hemoglobin, 30 nm x 20 nm, the diameter of the central cavity remained unchanged. Subtraction of the digitized and averaged images of the reassociated forms from those of the native hemoglobin suggested that the spatial localization of the fourth subunit, subunit M (16.7 kDa), was limited primarily to the periphery of the molecule.« less

Physiological, biochemical and histometric responses of Nile tilapia (Oreochromis niloticus L.) by dietary organic chromium (chromium picolinate) supplementation.

PubMed

Mehrim, Ahmed I

2014-05-01

Chromium has been recognized as a new and important micro-nutrient, essential for both human and animal nutrition. This study was conducted to evaluate the appropriateness and/or the use of safety level of dietary chromium picolinate (Cr-Pic), and its effects on the physiological responses, the histometric characteristics, and the chemical analysis of dorsal muscles of mono-sex Nile tilapia, Oreochromis niloticus. A total of 420 fingerlings (28.00 ± 0.96 g) were randomly distributed into 21 fiberglass tanks representing seven treatments at a rate of 20 fish m(-3). The control fish group (T1) was fed a Cr-Pic free basal diet. Other fish groups were fed the basal diet supplemented with 200 (T2), 400 (T3), 600 (T4), 800 (T5), 1000 (T6) and 1200 μg Cr-Pic kg(-1) diet (T7). Diets were offered to fish at a feeding rate of 3% of life body weight for 12 weeks. Results revealed that blood hematological parameters (hemoglobin, red blood cells, packed cell volume, mean corpuscular hemoglobin concentration, blood platelets, and white blood cells lymphocytes); serum biochemical measurements (total testosterone, high density lipoprotein, total protein, albumin, and globulin); and the dry matter and crude protein of the fish dorsal muscles all have significantly increased (P ⩽ 0.05) in the T3 treatment compared with the other treatments. Meanwhile, no significant differences were found among all treatments with regard to the histometric characteristics. It can be concluded that Cr-Pic at 400 μg kg(-1) diet (T3) seems to be the most appropriate level for O. niloticus fingerlings.

Hemoglobin Labeled by Radioactive Lysine

DOE R&D Accomplishments Database

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

1949-12-08

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

Plasma volume methodology: Evans blue, hemoglobin-hematocrit, and mass density transformations

NASA Technical Reports Server (NTRS)

Greenleaf, J. E.; Hinghofer-Szalkay, H.

1985-01-01

Methods for measuring absolute levels and changes in plasma volume are presented along with derivations of pertinent equations. Reduction in variability of the Evans blue dye dilution technique using chromatographic column purification suggests that the day-to-day variability in the plasma volume in humans is less than + or - 20 m1. Mass density determination using the mechanical-oscillator technique provides a method for measuring vascular fluid shifts continuously for assessing the density of the filtrate, and for quantifying movements of protein across microvascular walls. Equations for the calculation of volume and density of shifted fluid are presented.

Staphylococcus aureus Growth using Human Hemoglobin as an Iron Source

PubMed Central

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

2013-01-01

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

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

PubMed Central

Kawai, Kosuke; Villamor, Eduardo; Mugusi, Ferdinand M; Saathoff, Elmar; Urassa, Willy; Bosch, Ronald J; Spiegelman, Donna; Fawzi, Wafaie W

2012-01-01

BACKGROUND Patients with tuberculosis (TB) often suffer from profound malnutrition. OBJECTIVE To examine the patterns and predictors of change in nutritional and hemoglobin status during and after TB treatment. METHODS A total of 471 HIV-positive and 416 HIV-negative adults with pulmonary TB were prospectively followed in Dar es Salaam, Tanzania. All patients received 8 months TB treatment following enrollment. RESULTS About 40% of HIV-positive and 47% of HIV-negative TB patients had BMI <18.5 kg/m2 at baseline. About 94% of HIV-positive and 84% of HIV-negative participants were anemic at baseline. Both HIV-positive and HIV-negative patients experienced increases in BMI and hemoglobin concentrations over the course of TB treatment. Among HIV-positive patients, older age, low CD4 cell counts, and high viral load were independently associated with a smaller increase in BMI from baseline to 8 months. Female sex, older age, low CD4 cell counts, previous TB infection, and less money spent on food were independently associated with a smaller improvement in hemoglobin among HIV-positive patients during treatment. CONCLUSION HIV- positive TB patients, especially those with low CD4 cell counts, showed poor nutritional recovery during TB treatment. Adequate nutritional support should be considered during TB treatment. PMID:22283899

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

PubMed

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

2011-10-01

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

Prevalence of common hemoglobin variants in an afro-descendent Ecuadorian population

PubMed Central

2013-01-01

Background Hemoglobinopathies are among the most studied and frequent pathologies. These genetic disorders are considered a very important health care threat in many tropical countries. Ecuador is a tropical Latin-American country with an important presence of afro-descendants (7.2%). Afro-descendants are among the ethnic groups with higher frequency of hemoglobinopathies reported. Ambuqui is a region within the Imbabura province with an important presence of afro-descendants (>50%). The present study analyzed the frequency of the most common hemoglobin variants in an asymptomatic afro-descendent population using capillary electrophoresis. Findings From 114 individuals, 25 (22%) reported a hemoglobin variant. All individuals that presented hemoglobin variants were heterozygotes (asymptomatic). Hemoglobin S (sickle cell trait) was the most frequent variant found (14%), followed by hemoglobin E (4.4%), Fetal (2.6%) and C (1%). Conclusion Prevalence of hemoglobin S was consistent with populations from other countries, but it was lower than other Ecuadorian afro-descendent populations. Frequency of hemoglobin C was lower than other afro-descendent populations. This data suggests the possibility of gene flow from Native American individuals to the Ambuqui population there by lowering the frequency of their hemoglobin variants compared with other afro-descendant populations. Evaluating the frequency of hemoglobinopathies in Ecuadorian populations is essential. Despite the high frequency of these disorders, very few health care facilities implement hemoglobinopathies tests as a routine practice. PMID:23557107

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.

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

PubMed

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

2017-11-01

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

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 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.

A Relay Network of Extracellular Heme-Binding Proteins Drives C. albicans Iron Acquisition from Hemoglobin

PubMed Central

Kuznets, Galit; Vigonsky, Elena; Weissman, Ziva; Lalli, Daniela; Gildor, Tsvia; Kauffman, Sarah J.; Turano, Paola; Becker, Jeffrey; Lewinson, Oded; Kornitzer, Daniel

2014-01-01

Iron scavenging constitutes a crucial challenge for survival of pathogenic microorganisms in the iron-poor host environment. Candida albicans, like many microbial pathogens, is able to utilize iron from hemoglobin, the largest iron pool in the host's body. Rbt5 is an extracellular glycosylphosphatidylinositol (GPI)-anchored heme-binding protein of the CFEM family that facilitates heme-iron uptake by an unknown mechanism. Here, we characterize an additional C. albicans CFEM protein gene, PGA7, deletion of which elicits a more severe heme-iron utilization phenotype than deletion of RBT5. The virulence of the pga7−/− mutant is reduced in a mouse model of systemic infection, consistent with a requirement for heme-iron utilization for C. albicans pathogenicity. The Pga7 and Rbt5 proteins exhibit distinct cell wall attachment, and discrete localization within the cell envelope, with Rbt5 being more exposed than Pga7. Both proteins are shown here to efficiently extract heme from hemoglobin. Surprisingly, while Pga7 has a higher affinity for heme in vitro, we find that heme transfer can occur bi-directionally between Pga7 and Rbt5, supporting a model in which they cooperate in a heme-acquisition relay. Together, our data delineate the roles of Pga7 and Rbt5 in a cell surface protein network that transfers heme from extracellular hemoglobin to the endocytic pathway, and provide a paradigm for how receptors embedded in the cell wall matrix can mediate nutrient uptake across the fungal cell envelope. PMID:25275454

Blood smear

MedlinePlus

... in which there is excessive breakdown of hemoglobin ( thalassemia ) The presence of cells called burr cells may ... shaped cells may indicate: Myelofibrosis Severe iron deficiency Thalassemia major Cancer in the bone marrow Anemia caused ...

Light-induced protoporphyrin release from erythrocytes in erythropoietic protoporphyria.

PubMed Central

Sandberg, S; Brun, A

1982-01-01

The photohemolysis of normal erythrocytes incubated with protoporphyrin is reduced in the presence of albumin. When globin is added to normal erythrocytes loaded with protoporphyrin, protoporphyrin is bound to globin. During irradiation protoporphyrin moves from globin to the erythrocyte membrane and photohemolysis is initiated. Erythrocytes in patients with erythropoietic protoporphyria contain large amounts of protoporphyrin bound to hemoglobin. Upon irradiation of these cells in the absence of albumin, 40% of protoporphyrin and 80% of hemoglobin is released after 240 kJ/m2. The released protoporphyrin is hemoglobin bound. In contrast, when albumin is present only 8% of hemoglobin is released whereas protoporphyrin is released to 76%. The released protoporphyrin is albumin bound. A hypothesis for the release of erythrocyte protoporphyrin in erythropoietic protoporphyria without simultaneous hemolysis is proposed. Upon irradiation protoporphyrin photodamages its binding sites on hemoglobin, moves through the plasma membrane, and is bound to albumin in plasma. PMID:7107898

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.

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.

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.

Influence of prehospital fluid resuscitation on patients with multiple injuries in hemorrhagic shock in patients from the DGU trauma registry

PubMed Central

Huβmann, Björn; Lefering, Rolf; Taeger, Georg; Waydhas, Christian; Ruchholtz, Steffen

2011-01-01

Background: Severe bleeding as a result of trauma frequently leads to poor outcome by means of direct or delayed mechanisms. Prehospital fluid therapy is still regarded as the main option of primary treatment in many rescue situations. Our study aimed to assess the influence of prehospital fluid replacement on the posttraumatic course of severely injured patients in a retrospective analysis of matched pairs. Materials and Methods: We reviewed data from 35,664 patients recorded in the Trauma Registry of the German Society for Trauma Surgery (DGU). The following patients were selected: patients having an Injury Severity Score >16 points, who were ≥16 years of age, with trauma, excluding those with craniocerebral injuries, who were admitted directly to the participating hospitals from the accident site. All patients had recorded values for replaced volume and blood pressure, hemoglobin concentration, and units of packed red blood cells given. The patients were matched based on similar blood pressure characteristics, age groups, and type of accident to create pairs. Pairs were subdivided into two groups based on the volumes infused prior to hospitalization: group 1: 0-1500 (low), group 2: ≥2000 mL (high) volume. Results: We identified 1351 pairs consistent with the inclusion criteria. Patients in group 2 received significantly more packed red blood cells (group 1: 6.9 units, group 2: 9.2 units; P=0.001), they had a significantly reduced capacity of blood coagulation (prothrombin ratio: group 1: 72%, group 2: 61.4%; P≤0.001), and a lower hemoglobin value on arrival at hospital (group 1: 10.6 mg/dL, group 2: 9.1 mg/dL; P≤0.001). The number of ICU-free days concerning the first 30 days after trauma was significantly higher in group 1 (group 1: 11.5 d, group 2: 10.1 d; P≤0.001). By comparison, the rate of sepsis was significantly lower in the first group (group 1: 13.8%, group 2: 18.6%; P=0.002); the same applies to organ failure (group 1: 36.0%, group 2: 39.2%; P≤0.001). Conclusion: The high amounts of intravenous fluid replacement was related to early traumatic coagulopathy, organ failure, and sepsis rate. PMID:22090739

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.

Pitfalls in the biological diagnosis of common hemoglobin disorders.

PubMed

Wajcman, Henri; Moradkhani, Kamran

2015-01-01

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

Hypoxia increases erythropoiesis and decreases thrombocytopoiesis in mice: a comparison of two mouse strains.

PubMed

Cottrell, M B; Jackson, C W; McDonald, T P

1991-07-01

Several previous studies have shown that hypoxia increases erythropoiesis and decreases thrombocytopoiesis in mice. It has been postulated that the thrombocytopenia is caused by stem cell competition between the erythrocytic and megakaryocytic cell lines. In the present work, we compared the effects of severe hypoxia (5.5-6.0% O2) in both male and female C3H and BALB/c mice by measuring their abilities to produce red blood cells and platelets. All mice had significant increases in packed cell volumes and marked decreases in platelet production after hypoxia; however, there were significant differences in the degree of stimulation in the two mouse strains. After 14 days of hypoxia, the percentage of 35S incorporation into platelets, total circulating platelet counts and total circulating platelet masses were lower in C3H mice than in BALB/c mice, but platelet sizes were larger. Also, hypoxia caused greater changes in male mice than in female mice, with male C3H mice showing the greatest increase in packed cell volumes and the lowest platelet counts of all mice tested. The least responses were observed in female BALB/c mice. BALB/c mice had higher P50 (right-shifted O2 dissociation curves) and lower erythrocyte 2,3-diphosphoglycerate values than C3H mice, indicating a lower hemoglobin O2 affinity for BALB/c mice. The results indicate that the effects of hypoxia are not direct upon platelet production, but that the thrombocytopenia is a result of stimulation of erythropoiesis. These data support the stem cell competition hypothesis and illustrate that the degree of the inverse relationship between red blood cells and platelet production of hypoxic mice is dependent, to a large degree, upon the sex and strain of mice that are used.

Comparative evaluation of the depletion-red cell exchange program with the Spectra Optia and the isovolemic hemodilution-red cell exchange method with the COBE Spectra in sickle cell disease patients.

PubMed

Poullin, Pascale; Sanderson, Frederick; Bernit, Emmanuelle; Brun, Marion; Berdah, Yael; Badens, Catherine

2016-10-01

This study aims to compare in patients with sickle cell disease (SCD), the technical performance and packed red blood cell unit consumption between the automated depletion/Red Blood Cell exchange (RBCx) program (Spectra Optia Apheresis System) with the isovolemic hemodilution (IHD)/RBCx procedure (COBE Spectra Apheresis System) in a routine clinical setting. We retrospectively reviewed the data of 23 patients treated between October 2010 and August 2013 who underwent repeated RBCx on both apheresis systems for preventive indications. Each patient was their own control and had undergone two procedures on each system, totaling 46 sessions per group. On Spectra Optia, we performed the automated depletion/RBCx program. For COBE Spectra, we used a modified IHD/RBCx protocol. All patients had an initial 250 mL depletion offset by a 5% albumin prior to the exchange procedure, for the respective device, with leucodepleted Rh/Kell compatible and cross-matched RBC packs. All procedures were well tolerated except three mild febrile nonhemolytic reactions. Postprocedure hemoglobin S (HbS), fraction of cells remaining (FCR), procedure duration and processed blood and anticoagulant volumes were comparable in the two groups. However, the RBCx volume was significantly higher for the Spectra Optia group (+71 mL, P = 0.01), with no significant difference in the number of RBC units used. Technical performance and packed RBC unit consumption were not compromised when switching from the COBE Spectra IHD/RBCx protocol to the depletion/RBCx protocol on the Spectra Optia. Tolerability was equal for both protocols. J. Clin. Apheresis 31:429-433, 2016. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

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

PubMed Central

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

2017-01-01

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

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

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

Inoguchi, Noriko; Mizuno, Nobuhiro; Baba, Seiki

2017-03-31

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

Interactions between peroxiredoxin 2, hemichrome and the erythrocyte membrane.

PubMed

Bayer, Simone B; Low, Felicia M; Hampton, Mark B; Winterbourn, Christine C

2016-12-01

Peroxiredoxin 2 (Prx2) is an abundant antioxidant protein in erythrocytes that protects against hemolytic anemia resulting from hemoglobin oxidation and Heinz body formation. A small fraction of Prx2 is bound to the cell membrane, but the mechanism and relevance of binding are not clear. We have investigated Prx2 interactions with the erythrocyte membrane and oxidized hemoglobin and whether these interactions are dependent on Prx2 redox state. Membrane binding of Prx2 in erythrocytes decreased when the cells were treated with H 2 O 2 , but studies with purified Prx2 and isolated ghosts showed that the interaction was independent of Prx2 redox state. Hemoglobin oxidation leads to the formation of hemichrome, a denatured form of the protein that binds to Band3 protein in the cell membrane as part of the senescence process and is a precursor of Heinz bodies. Hemichrome competed with Prx2 and decreased Prx2 binding to the membrane, potentially explaining the decreased binding in oxidant-exposed cells. The increased membrane binding of Prx2 seen with increasing intracellular calcium was less sensitive to H 2 O 2 or hemichrome, suggesting an alternative mode of binding. Prx2 was also shown to exhibit chaperone-like activity by retarding the precipitation of pre-formed hemichrome. Our results suggest that Prx2, by restricting membrane binding of hemichrome, could impede Band3 clustering and exposure of senescence antigens. This mechanism, plus the observed chaperone activity for oxidized hemoglobin, may help protect against hemolytic anemia.

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.

Ischemic duodenal ulcer, an unusual presentation of sickle cell disease.

PubMed

Julka, Rahul N; Aduli, Farshad; Lamps, Laura W; Olden, Kevin W

2008-03-01

Sickle cell disease is caused by molecular abnormalities in the formation of hemoglobin, leading to pain crisis from recurrent vascular occlusion by sickled hemoglobin. Impaired flow in the microvasculature can lead to ischemia, tissue infarction and ulceration. Abdominal pain, a common complaint in sickle cell disease, can be due to an uncommon etiology, ischemic duodenal ulceration. This is due to primary mucosal infarction caused by sickling, leading to poor healing of infarcted areas. Prompt endoscopic and/or urgent surgical intervention should be considered, particularly if anticoagulation is an issue, as proton pump inhibitor use is ineffective in healing this type of ulcer.

Topical Olive Leaf Extract Improves Healing of Oral Mucositis in Golden Hamsters.

PubMed

Showraki, Najmeh; Mardani, Maryam; Emamghoreishi, Masoumeh; Andishe-Tadbir, Azadeh; Aram, Alireza; Mehriar, Peiman; Omidi, Mahmoud; Sepehrimanesh, Masood; Koohi-Hosseinabadi, Omid; Tanideh, Nader

2016-12-01

Oral mucositis (OM) is a common side effect of anti-cancer drugs and needs significant attention for its prevention. This study aimed to evaluate the healing effects of olive leaf extract on 5-fluorouracil-induced OM in golden hamster. OM was induced in 63 male golden hamsters by the combination of 5-fluorouracil injections (days 0, 5 and 10) and the abrasion of the cheek pouch (days 3 and 4). On day 12, hamsters were received topical olive leaf extract ointment, base of ointment, or no treatment (control) for 5 days. Histopathology evaluations, blood examinations, and tissue malondialdehyde level measurement were performed 1, 3 and 5 days after treatments. Histopathology score and tissue malondialdehyde level were significantly lower in olive leaf extract treated group in comparison with control and base groups ( p = 0.000). Significant decreases in white blood cell, hemoglobin, hematocrit , and mean corpuscular volume and an increase in mean corpuscular hemoglobin concentration were observed in olive leaf extract treated group in comparison with control and base groups ( p < 0.05). Our findings demonstrated that daily application of olive leaf extract ointment had healing effect on 5-fluorouracil induced OM in hamsters. Moreover, the beneficial effect of olive leaf extract on OM might be due to its antioxidant and anti-inflammatory properties.

Red Blood Cell Transfusion Need for Elective Primary Posterior Lumbar Fusion in A High-Volume Center for Spine Surgery

PubMed Central

Ristagno, Giuseppe; Beluffi, Simonetta; Tanzi, Dario; Belloli, Federica; Carmagnini, Paola; Croci, Massimo; D’Aviri, Giuseppe; Menasce, Guido; Pastore, Juan C.; Pellanda, Armando; Pollini, Alberto; Savoia, Giorgio

2018-01-01

(1) Background: This study evaluated the perioperative red blood cell (RBC) transfusion need and determined predictors for transfusion in patients undergoing elective primary lumbar posterior spine fusion in a high-volume center for spine surgery. (2) Methods: Data from all patients undergoing spine surgery between 1 January 2014 and 31 December 2016 were reviewed. Patients’ demographics and comorbidities, perioperative laboratory results, and operative time were analyzed in relation to RBC transfusion. Multivariate logistic regression analysis was performed to identify the predictors of transfusion. (3) Results: A total of 874 elective surgeries for primary spine fusion were performed over the three years. Only 54 cases (6%) required RBC transfusion. Compared to the non-transfused patients, transfused patients were mainly female (p = 0.0008), significantly older, with a higher ASA grade (p = 0.0002), and with lower pre-surgery hemoglobin (HB) level and hematocrit (p < 0.0001). In the multivariate logistic regression, a lower pre-surgery HB (OR (95% CI) 2.84 (2.11–3.82)), a higher ASA class (1.77 (1.03–3.05)) and a longer operative time (1.02 (1.01–1.02)) were independently associated with RBC transfusion. (4) Conclusions: In the instance of elective surgery for primary posterior lumbar fusion in a high-volume center for spine surgery, the need for RBC transfusion is low. Factors anticipating transfusion should be taken into consideration in the patient’s pre-surgery preparation. PMID:29385760

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.

Transcatheter Arterial Embolization of Angiographically Visible and Occult Renal Capsular Artery Hemorrhage in 28 Patients.

PubMed

Park, Hyo Jung; Shin, Ji Hoon; Han, Ki-Chang; Yoon, Hyun-Ki; Ko, Gi-Young; Sung, Kyu-Bo

2016-07-01

To evaluate the effectiveness and safety of transcatheter arterial embolization to control bleeding from the renal capsular artery (RCA). Embolization was performed in 28 patients (14 men; mean age, 49.7 y). Presence and type of previous invasive procedures, initial presentation, and coagulation profile were reviewed. Any preceding abdominal computed tomography (CT) findings were analyzed. Angiographic findings were categorized as active bleeding, suspicious for bleeding, or no bleeding. Technical and clinical success and clinical outcomes were evaluated. Changes in hemoglobin level and transfusion volume of packed red blood cells (pBRCs) before and after embolization were evaluated with the paired t test and Wilcoxon signed-rank test, respectively. Technical and clinical success rates of therapeutic embolization for active bleeding (n = 11) were 90.9% and 80%, respectively. One case of technical failure (5.9%) and 3 cases of postembolization bleeding (18.7%) were noted in the prophylactic embolization group in patients with suspicion of bleeding (n = 13) or no bleeding (n = 4). Transient renal insufficiency occurred in 4 patients (14.3%). The average hemoglobin level and volume of transfused pBRCs changed from 8.1 g/dL to 9.9 g/dL and from 871 mL to 543 mL, respectively (P < .05). Extravasation of contrast media or acute hematoma in the right subhepatic or perirenal space on CT was noted in 21 patients (78%). Embolization can provide an effective and safe method to control RCA bleeding. Perirenal invasive procedures and signs of active or recent right subhepatic or perirenal hemorrhage should raise the suspicion of an RCA source. Copyright © 2016 SIR. Published by Elsevier Inc. All rights reserved.

Dhatrilauha: Right choice for iron deficiency anemia in pregnancy

PubMed Central

Roy, Anuradha; Dwivedi, Manjari

2014-01-01

Background: Anemia in pregnancy is multi-factorial. Iron deficiency anemia (IDA) is the most common one. Major cause is increased demand of iron during pregnancy. In Ayurveda, under Pandu-Roga the features of anemia are described. It is characterized by Vaivarnyata or Varnanasha (change/destruction in normal color of the body), a disorder of Pitta vitiation. Ayurvedic management is an effective way of curing anemia in general by a large number of Lauha preparations of which Dhatrilauha has been used widely for centuries. Aim: To evaluate the effect of Dhatrilauha in the management of IDA based on the scientific parameters among pregnant patients. Materials and Methods: A total of 58 cases were selected by simple randomized sampling method as per inclusion criteria of pregnant women between 4th and 7th months of pregnancy with a clinical diagnosis and laboratory confirmation of IDA. Dhatrilauha 500 mg in two divided doses after food with normal potable water were given for 45 days with three follow-ups, each of 15 days intervals. Final assessment was done after completion of 45 days and results were statistically analyzed by using Cochran's Q-test and Student's t-test. Results: Dhatrilauha showed statistically significant (P < 0.01) improvement in the majority of sign-symptoms and objective parameters such as weakness, fatigue, palpitation, effort intolerance, breathlessness, heartburn, pallor, constipation, hemoglobin, red blood cells (RBC), hematocrit, mean corpuscular volume, mean corpuscular hemoglobin concentration, RBC distribution width, mean platelet volume, serum iron, and total iron binding capacity. Conclusion: Dhatrilauha possesses many fold effectiveness in anemia (IDA), which was evidenced with the significant results obtained in the majority of parameters in this study. PMID:25972720

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

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.

Preliminary Crystallographic Study of Hemoglobin from Buffalo (Bubalus bubalis): A Low Oxygen Affinity Species.

PubMed

Balasubramanian, Moovarkumudalvan; Moorthy, Ponnuraj Sathya; Neelagandan, Kamariah; Ponnuswamy, Mondikalipudur Nanjappa Gounder

2009-01-01

Hemoglobin is a tetrameric, iron-containing metalloprotein, which plays a vital role in the transportation of oxygen from lungs to tissues and carbon dioxide back to lungs. Though good amount of work has already been done on hemoglobins, the scarcity of data on three dimensional structures pertaining to low oxygen affinity hemoglobins from mammalian species, motivated our group to work on this problem specifically. Herein, we report the preliminary crystallographic analysis of buffalo hemoglobin, which belongs to low oxygen affinity species. The buffalo blood was collected, purified by anion exchange chromatography and crystallized with PEG 3350 using 50mM phosphate buffer at pH 6.7 as a precipitant by hanging drop vapor diffusion method. Data collection was carried out using mar345dtb image plate detector system. Buffalo hemoglobin crystallizes in orthorhombic space group P2(1)2(1)2(1) with one whole biological molecule (alpha2beta2) in the asymmetric unit with cell dimensions a=63.064A, b=74.677A, c=110.224A.

Hematology from embryo to adult in the bobwhite quail (Colinus virginianus): Differential effects in the adult of clutch, sex and hypoxic incubation.

PubMed

Flores-Santin, Josele; Rojas Antich, Maria; Tazawa, Hiroshi; Burggren, Warren W

2018-04-01

Hematology and its regulation in developing birds have been primarily investigated in response to relatively short-term environmental challenges in the embryo. Yet, whether any changes induced in the embryo persist into adulthood as a hematological form of "fetal programming" is unknown. We hypothesized that: 1) chronic as opposed to acute hypoxic incubation will alter hematological respiratory variables in embryos of bobwhite quail (Colinus virginianus), and 2) alterations first appearing in the embryo will persist into hatchlings through into adulthood. To test these hypotheses, we first developed an embryo-to-adult profile of normal hematological development by measuring hematocrit (Hct), red blood cell concentration ([RBC]), hemoglobin concentration ([Hb]), mean corpuscular volume, mean corpuscular hemoglobin and mean corpuscular hemoglobin concentration, as well plasma osmolality. Hct, [RBC] and [Hb] in normoxic-incubated birds (controls) steadily increased from ~22%, ~1.6 × 10 6  μL -1 and ~7 g% in day 12 embryos to almost double the values at maturity in adult birds. Both cohort and sex affected hematology of normoxic-incubated birds. A second population, incubated from day 0 (d0) in 15% O 2 , surprisingly revealed little or no significant difference from controls in hematology in embryos. In hatchlings and adults, hypoxic incubation caused no significant modification to any variables. Compared to major hematological effects caused by hypoxic incubation in chickens, the hematology of the bobwhite quail embryo appears to be minimally affected by hypoxic incubation, with very few effects induced during hypoxic incubation actually persisting into adulthood. Copyright © 2018 Elsevier Inc. All rights reserved.

Functional and anatomical evidence of cerebral tissue hypoxia in young sickle cell anemia mice.

PubMed

Cahill, Lindsay S; Gazdzinski, Lisa M; Tsui, Albert Ky; Zhou, Yu-Qing; Portnoy, Sharon; Liu, Elaine; Mazer, C David; Hare, Gregory Mt; Kassner, Andrea; Sled, John G

2017-03-01

Cerebral ischemia is a significant source of morbidity in children with sickle cell anemia; however, the mechanism of injury is poorly understood. Increased cerebral blood flow and low hemoglobin levels in children with sickle cell anemia are associated with increased stroke risk, suggesting that anemia-induced tissue hypoxia may be an important factor contributing to subsequent morbidity. To better understand the pathophysiology of brain injury, brain physiology and morphology were characterized in a transgenic mouse model, the Townes sickle cell model. Relative to age-matched controls, sickle cell anemia mice demonstrated: (1) decreased brain tissue pO 2 and increased expression of hypoxia signaling protein in the perivascular regions of the cerebral cortex; (2) elevated basal cerebral blood flow , consistent with adaptation to anemia-induced tissue hypoxia; (3) significant reduction in cerebrovascular blood flow reactivity to a hypercapnic challenge; (4) increased diameter of the carotid artery; and (5) significant volume changes in white and gray matter regions in the brain, as assessed by ex vivo magnetic resonance imaging. Collectively, these findings support the hypothesis that brain tissue hypoxia contributes to adaptive physiological and anatomic changes in Townes sickle cell mice. These findings may help define the pathophysiology for stroke in children with sickle cell anemia.

Functional and anatomical evidence of cerebral tissue hypoxia in young sickle cell anemia mice

PubMed Central

Gazdzinski, Lisa M; Tsui, Albert KY; Zhou, Yu-Qing; Portnoy, Sharon; Liu, Elaine; Mazer, C David; Hare, Gregory MT; Kassner, Andrea; Sled, John G

2016-01-01

Cerebral ischemia is a significant source of morbidity in children with sickle cell anemia; however, the mechanism of injury is poorly understood. Increased cerebral blood flow and low hemoglobin levels in children with sickle cell anemia are associated with increased stroke risk, suggesting that anemia-induced tissue hypoxia may be an important factor contributing to subsequent morbidity. To better understand the pathophysiology of brain injury, brain physiology and morphology were characterized in a transgenic mouse model, the Townes sickle cell model. Relative to age-matched controls, sickle cell anemia mice demonstrated: (1) decreased brain tissue pO2 and increased expression of hypoxia signaling protein in the perivascular regions of the cerebral cortex; (2) elevated basal cerebral blood flow , consistent with adaptation to anemia-induced tissue hypoxia; (3) significant reduction in cerebrovascular blood flow reactivity to a hypercapnic challenge; (4) increased diameter of the carotid artery; and (5) significant volume changes in white and gray matter regions in the brain, as assessed by ex vivo magnetic resonance imaging. Collectively, these findings support the hypothesis that brain tissue hypoxia contributes to adaptive physiological and anatomic changes in Townes sickle cell mice. These findings may help define the pathophysiology for stroke in children with sickle cell anemia. PMID:27165012

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.

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...

Gardos pathway to sickle cell therapies?

PubMed

Joiner, Clinton H

2008-04-15

In this issue of Blood, Ataga and colleagues report that treatment of sickle cell disease patients with senicapoc, a Gardos channel inhibitor, reduces the number of dehydrated cells, increases hemoglobin levels, and diminishes hemolysis.

Autologous cytokine-induced killer cell immunotherapy may improve overall survival in advanced malignant melanoma patients.

PubMed

Zhang, Yong; Zhu, Yu'nan; Zhao, Erjiang; He, Xiaolei; Zhao, Lingdi; Wang, Zibing; Fu, Xiaomin; Qi, Yalong; Ma, Baozhen; Song, Yongping; Gao, Quanli

2017-11-01

Our study was conducted to explore the efficacy of autologous cytokine-induced killer (CIK) cells in patients with advanced malignant melanoma. Materials & Methods: Here we reviewed 113 stage IV malignant melanoma patients among which 68 patients received CIK cell immunotherapy alone, while 45 patients accepted CIK cell therapy combined with chemotherapy. Results: We found that the median survival time in CIK cell group was longer than the combined therapy group (21 vs 15 months, p = 0.07). In addition, serum hemoglobin level as well as monocyte proportion and lymphocyte count were associated with patients' survival time. These indicated that CIK cell immunotherapy might extend survival time in advanced malignant melanoma patients. Furthermore, serum hemoglobin level, monocyte proportion and lymphocyte count could be prognostic indicators for melanoma.

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.

Low Volume Aerobic Training Heightens Muscle Deoxygenation in Early Post-Angina Pectoris Patients.

PubMed

Takagi, Shun; Murase, Norio; Kime, Ryotaro; Niwayama, Masatsugu; Osada, Takuya; Katsumura, Toshihito

2016-01-01

The aim of this study was to investigate the effect of low volume aerobic exercise training on muscle O2 dynamics during exercise in early post-angina pectoris (AP) patients, as a pilot study. Seven AP patients (age: 72 ± 6 years) participated in aerobic exercise training for 12 weeks. Training consisted of continuous cycling exercise for 30 min at the individual's estimated lactate threshold, and the subjects trained for 15 ± 5 exercise sessions over 12 weeks. Before and after training, the subjects performed ramp cycling exercise until exhaustion. Muscle O2 saturation (SmO2) and relative changes from rest in deoxygenated hemoglobin concentration (∆Deoxy-Hb) and total hemoglobin concentration (∆Total-Hb) were monitored at the vastus lateralis by near infrared spatial resolved spectroscopy during exercise. The SmO2 was significantly lower and ∆Deoxy-Hb was significantly higher after training than before training, while there were no significant changes in ∆Total-Hb. These results indicated that muscle deoxygenation and muscle O2 extraction were potentially heightened by aerobic exercise training in AP patients, even though the exercise training volume was low.

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

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.

Portal hypertension and hypersplenism in extrahepatic portal venous obstruction: Are they related?

PubMed

Kilambi, Ragini; Singh, Anand Narayan; Madhusudhan, Kumble Seetharama; Pal, Sujoy; Saxena, Renu; Shalimar; Dash, Nihar Ranjan; Sahni, Peush

2018-06-23

Portal hypertension (PHT) due to extrahepatic portal venous obstruction (EHPVO) is common in developing countries. Hypersplenism is a near-constant feature of EHPVO, but its significance, unlike in cirrhotics, is unknown. We aimed to study the relationship between hypersplenism and the severity of PHT in patients with EHPVO. This prospective study was done at a tertiary care center from January 2014 to August 2015. All patients with EHPVO who underwent a splenectomy and a shunt or devascularization were included. Data regarding clinical profile, preoperative parameters, and intraoperative details were recorded. The correlation was studied between hypersplenism and the intraoperatively measured portal pressures and markers of PHT. Of the 40 patients studied (mean [SD] age 22.4 [8.4] years), hematological hypersplenism was present in 39 (97.5%). The mean (SD) hemoglobin, total leukocyte counts (TLC), and platelet counts were 9.9 (2.4) g/dL, 2971 (1239) cells/mm 3 , and 66,400 (32047) cells/mm 3 , respectively. The mean (SD) sonographic spleen volume (SV), splenic weight, and intraoperative portal pressure were 1084.7 (553.9) cm 3 , 1088.7 (454.7) g, and 35.6 (5.1) mmHg, respectively. The TLC and platelet counts correlated inversely with the portal pressure. Additionally, the platelet counts correlated negatively with eradicated variceal status, SV, and weight; hemoglobin with SV and weight; and TLC with SV. Multivariate analysis showed the platelet counts were an independent predictor of portal pressures and platelet counts ≤ 53,500 cells/mm 3 indicated significantly high portal pressures. The platelet counts showed a significant inverse correlation with portal pressures in patients with EHPVO and may be used as surrogate markers of PHT. A platelet count ≤ 53,500 cells/mm 3 is predictive of significantly high pressures.

In vivo multispectral photoacoustic and photothermal flow cytometry with multicolor dyes: a potential for real-time assessment of circulation, dye-cell interaction, and blood volume.

PubMed

Proskurnin, Mikhail A; Zhidkova, Tatyana V; Volkov, Dmitry S; Sarimollaoglu, Mustafa; Galanzha, Ekaterina I; Mock, Donald; Nedosekin, Dmitry A; Zharov, Vladimir P

2011-10-01

Recently, photoacoustic (PA) flow cytometry (PAFC) has been developed for in vivo detection of circulating tumor cells and bacteria targeted by nanoparticles. Here, we propose multispectral PAFC with multiple dyes having distinctive absorption spectra as multicolor PA contrast agents. As a first step of our proof-of-concept, we characterized high-speed PAFC capability to monitor the clearance of three dyes (Indocyanine Green [ICG], Methylene Blue [MB], and Trypan Blue [TB]) in an animal model in vivo and in real time. We observed strong dynamic PA signal fluctuations, which can be associated with interactions of dyes with circulating blood cells and plasma proteins. PAFC demonstrated enumeration of circulating red and white blood cells labeled with ICG and MB, respectively, and detection of rare dead cells uptaking TB directly in bloodstream. The possibility for accurate measurements of various dye concentrations including Crystal Violet and Brilliant Green were verified in vitro using complementary to PAFC photothermal (PT) technique and spectrophotometry under batch and flow conditions. We further analyze the potential of integrated PAFC/PT spectroscopy with multiple dyes for rapid and accurate measurements of circulating blood volume without a priori information on hemoglobin content, which is impossible with existing optical techniques. This is important in many medical conditions including surgery and trauma with extensive blood loss, rapid fluid administration, and transfusion of red blood cells. The potential for developing a robust clinical PAFC prototype that is safe for human, and its applications for studying the liver function are further highlighted. Copyright © 2011 International Society for Advancement of Cytometry.

A Randomized Controlled Trial of Low-Dose Tranexamic Acid versus Placebo to Reduce Red Blood Cell Transfusion During Complex Multilevel Spine Fusion Surgery.

PubMed

Carabini, Louanne M; Moreland, Natalie C; Vealey, Ryan J; Bebawy, John F; Koski, Tyler R; Koht, Antoun; Gupta, Dhanesh K; Avram, Michael J

2018-02-01

Multilevel spine fusion surgery for adult deformity correction is associated with significant blood loss and coagulopathy. Tranexamic acid reduces blood loss in high-risk surgery, but the efficacy of a low-dose regimen is unknown. Sixty-one patients undergoing multilevel complex spinal fusion with and without osteotomies were randomly assigned to receive low-dose tranexamic acid (10 mg/kg loading dose, then 1 mg·kg -1 ·hr -1 throughout surgery) or placebo. The primary outcome was the total volume of red blood cells transfused intraoperatively. Thirty-one patients received tranexamic acid, and 30 patients received placebo. Patient demographics, risk of major transfusion, preoperative hemoglobin, and surgical risk of the 2 groups were similar. There was a significant decrease in total volume of red blood cells transfused (placebo group median 1460 mL vs. tranexamic acid group 1140 mL; median difference 463 mL, 95% confidence interval 15 to 914 mL, P = 0.034), with a decrease in cell saver transfusion (placebo group median 490 mL vs. tranexamic acid group 256 mL; median difference 166 mL, 95% confidence interval 0 to 368 mL, P = 0.042). The decrease in packed red blood cell transfusion did not reach statistical significance (placebo group median 1050 mL vs. tranexamic acid group 600 mL; median difference 300 mL, 95% confidence interval 0 to 600 mL, P = 0.097). Our results support the use of low-dose tranexamic acid during complex multilevel spine fusion surgery to decrease total red blood cell transfusion. Copyright © 2017 Elsevier Inc. All rights reserved.

Transverse water relaxation in whole blood and erythrocytes at 3T, 7T, 9.4T, 11.7T and 16.4T; determination of intracellular hemoglobin and extracellular albumin relaxivities.

PubMed

Grgac, Ksenija; Li, Wenbo; Huang, Alan; Qin, Qin; van Zijl, Peter C M

2017-05-01

Blood is a physiological substance with multiple water compartments, which contain water-binding proteins such as hemoglobin in erythrocytes and albumin in plasma. Knowing the water transverse (R 2 ) relaxation rates from these different blood compartments is a prerequisite for quantifying the blood oxygenation level-dependent (BOLD) effect. Here, we report the Carr-Purcell-Meiboom-Gill (CPMG) based transverse (R 2CPMG ) relaxation rates of water in bovine blood samples circulated in a perfusion system at physiological temperature in order to mimic blood perfusion in humans. R 2CPMG values of blood plasma, lysed packed erythrocytes, lysed plasma/erythrocyte mixtures, and whole blood at 3 T, 7 T, 9.4 T, 11.7 T and 16.4 T were measured as a function of hematocrit or hemoglobin concentration, oxygenation, and CPMG inter-echo spacing (τ cp ). R 2CPMG in lysed cells showed a small τ cp dependence, attributed to the water exchange rate between free and hemoglobin-bound water to be much faster than τ cp . This was contrary to the tangential dependence in whole blood, where a much slower exchange between cells and blood plasma applies. Whole blood data were fitted as a function of τ cp using a general tangential correlation time model applicable for exchange as well as diffusion contributions to R 2CPMG , and the intercept R 20blood at infinitely short τ cp was determined. The R 20blood values at different hematocrit and the R 2CPMG values of lysed erythrocyte/plasma mixtures at different hemoglobin concentration were used to determine the relaxivity of hemoglobin inside the erythrocyte (r 2Hb ) and albumin (r 2Alb ) in plasma. The r 2Hb values obtained from lysed erythrocytes and whole blood were comparable at full oxygenation. However, while r 2Hb determined from lysed cells showed a linear dependence on oxygenation, this dependence became quadratic in whole blood. This possibly suggests an additional relaxation effect inside intact cells, perhaps due to hemoglobin proximity to the erythrocyte membrane. However, we cannot exclude that this is a consequence of the simple tangential model used to remove relaxation contributions from exchange and diffusion. The extensive data set presented should be useful for future theory development for the transverse relaxation of blood. Copyright © 2016 Elsevier Inc. All rights reserved.

Outcomes after 18 months of eliglustat therapy in treatment‐naïve adults with Gaucher disease type 1: The phase 3 ENGAGE trial

PubMed Central

Lukina, Elena; Ben Turkia, Hadhami; Shankar, Suma P.; Baris, Hagit; Ghosn, Marwan; Mehta, Atul; Packman, Seymour; Pastores, Gregory; Petakov, Milan; Assouline, Sarit; Balwani, Manisha; Danda, Sumita; Hadjiev, Evgueniy; Ortega, Andres; Gaemers, Sebastiaan J. M.; Tayag, Regina; Peterschmitt, M. Judith

2017-01-01

Abstract Eliglustat, an oral substrate reduction therapy, is a first‐line treatment for adults with Gaucher disease type 1 (GD1) who are poor, intermediate, or extensive CYP2D6 metabolizers (>90% of patients). In the primary analysis of the Phase 3 ENGAGE trial (NCT00891202), eliglustat treatment for 9 months resulted in significant reductions in spleen and liver volumes and increases in hemoglobin concentration and platelet count compared with placebo. We report 18‐month outcomes of patients who entered the trial extension period, in which all patients received eliglustat. Of 40 trial patients, 39 entered the extension period, and 38 completed 18 months. Absolute values and percent change over time were determined for spleen and liver volume, hemoglobin concentration, platelet count, bone mineral density, bone marrow burden, and Gaucher disease biomarkers. For patients randomized to eliglustat in the double‐blind period, continuing treatment with eliglustat for 9 more months resulted in incremental improvement of all disease parameters. For patients randomized to placebo in the double‐blind period, eliglustat treatment during the 9‐month, open‐label period resulted in significant decrease of spleen and liver volumes and significant increase of hemoglobin and platelets, with a similar rate of change to patients who had received eliglustat in the double‐blind period. Eliglustat treatment was also associated with improvement in bone marrow burden score, bone mineral density, and established biomarkers of Gaucher disease, including reduction of the bioactive lipid, glucosylsphingosine. These findings underscore the efficacy of eliglustat in treatment‐naïve patients. Eliglustat was well‐tolerated, and there were no new safety concerns with longer‐term exposure. PMID:28762527

The repeated-bout effect: influence on biceps brachii oxygenation and myoelectrical activity.

PubMed

Muthalib, Makii; Lee, Hoseong; Millet, Guillaume Y; Ferrari, Marco; Nosaka, Kazunori

2011-05-01

This study investigated biceps brachii oxygenation and myoelectrical activity during and following maximal eccentric exercise to better understand the repeated-bout effect. Ten men performed two bouts of eccentric exercise (ECC1, ECC2), consisting of 10 sets of 6 maximal lengthening contractions of the elbow flexors separated by 4 wk. Tissue oxygenation index minimum amplitude (TOI(min)), mean and maximum total hemoglobin volume by near-infrared spectroscopy, torque, and surface electromyography root mean square (EMG(RMS)) during exercise were compared between ECC1 and ECC2. Changes in maximal voluntary isometric contraction (MVC) torque, range of motion, plasma creatine kinase activity, muscle soreness, TOI(min), and EMG(RMS) during sustained (10-s) and 30-repeated isometric contraction tasks at 30% (same absolute force) and 100% MVC (same relative force) for 4 days postexercise were compared between ECC1 and ECC2. No significant differences between ECC1 and ECC2 were evident for changes in torque, TOI(min), mean total hemoglobin volume, maximum total hemoglobin volume, and EMG(RMS) during exercise. Smaller (P < 0.05) changes and faster recovery of muscle damage markers were evident following ECC2 than ECC1. During 30% MVC tasks, TOI(min) did not change, but EMG(RMS) increased 1-4 days following ECC1 and ECC2. During 100% MVC tasks, EMG(RMS) did not change, but torque and TOI(min) decreased 1-4 days following ECC1 and ECC2. TOI(min) during 100% MVC tasks and EMG(RMS) during 30% MVC tasks recovered faster (P < 0.05) following ECC2 than ECC1. We conclude that the repeated-bout effect cannot be explained by altered muscle activation or metabolic/hemodynamic changes, and the faster recovery in muscle oxygenation and activation was mainly due to faster recovery of force.

Effects of feeding and fasting on wolf blood and urine characteristics

USGS Publications Warehouse

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

1987-01-01

Feeding and fasting trials were conducted with 2 groups (A and B) of 4 gray wolves (Canis lupus) each during January 1980. The groups were fed for 9 days and fasted for 10 days in a cross-over design. Blood and urine samples and weight data were collected every 2-3 days during each trial. Hemoglobin (Hb) concentrations, red blood cell (RBC) counts, and hematocrits (HCT) were elevated in both groups during fasting. White blood cell (WBC) counts, serum urea nitrogen (SUN), triiodothyronine (T3), and insulin concentrations decreased during fasting in Groups A and B. Mean corpuscular hemoglobin concentration (MCHC), serum cholesterol, triglyceride, and iron (Fe) concentrations were diminished in fasted Group A wolves compared to fed Group B. Creatine phosphokinase (CPK) concentrations were elevated in fed Group A wolves. Serum creatinine (C) concentrations were reduced in both groups during feeding. Urinary urea: creatinine (U:C), potassium:creatine (K:C), and sodium:creatinine (Na:C, pooled Group A and B data) ratios decreased in fasted wolves. Differences were not found between fed and fasted wolves for mean corpuscular volume (MCV), serum cortisol, glucose, calcium (Ca), bilirubin, serum glutamate-oxaloacetate transaminase (SGOT), serum glutamate-pyruvate transaminase (SGOT), serum glutamate-pyruvate transaminase (SGPT), alkaline phosphatase, and luteinizing hormone (LH) concentrations, total iron binding capacity (TIBC), and urinary calcium: creatine (Ca:C) ratios. Analysis of multiple blood or urine samples collected from free-ranging wolves would be useful in enabling researches and managers to identify the nutritional status and general health of wolves over time.

In Vitro Evaluation of the Fresenius Kabi CATSmart Autotransfusion System.

PubMed

Alberts, Melissa; Groom, Robert C; Walczak, Richard; Kramer, Robert; Karpiel, Adrienne; Dieter, Jeanette; Sheth, Lisa; Greene, Nathaniel H; Jooste, Edmund H

2017-06-01

Use of autotransfusion systems to collect, wash, and concentrate shed blood during surgical procedures is a widely used method for reducing postoperative anemia and the need for blood transfusions. The aim of this study was to evaluate the CATSmart Continuous Autotransfusion System wash program performance with small (200 or 700 mL) and large volumes (1,000 mL) of shed blood and to determine non-inferiority of the CATSmart to the C.A.T.S plus system. Human whole blood was collected in citrate phosphate dextrose, diluted, and divided into two aliquots to be processed as a pair using the C.A.T.S plus and CATSmart systems with their corresponding wash programs: low-volume, high quality/smart, or emergency wash. Final packed red cell product was analyzed for red blood cell (RBC), white blood cell, and platelet counts; hemoglobin; hemolysis; RBC recovery rates; and elimination of albumin, total protein, and potassium. The mean hematocrit (HCT) after processing with CATSmart and C.A.T.S plus systems were 59.63% and 57.71%, respectively. The calculated overall RBC recovery rates on the CATSmart and C.A.T.S plus systems were 85.41% and 84.99%, respectively. Elimination of albumin (97.5%, 98.0%), total proteins (97.1%, 97.5%), and potassium (92.1%, 91.9%) were also calculated for the CATSmart and C.A.T.S plus systems. The CATSmart and C.A.T.S plus systems both provided a high-quality product in terms of HCT, protein elimination, and hemolysis rates across the range of tested shed blood volumes and all wash programs. The study was able to confirm the CATSmart is non-inferior to the C.A.T.S plus system.

In Vitro Evaluation of the Fresenius Kabi CATSmart Autotransfusion System

PubMed Central

Alberts, Melissa; Groom, Robert C.; Walczak, Richard; Kramer, Robert; Karpiel, Adrienne; Dieter, Jeanette; Sheth, Lisa; Greene, Nathaniel H.; Jooste, Edmund H.

2017-01-01

Abstract: Use of autotransfusion systems to collect, wash, and concentrate shed blood during surgical procedures is a widely used method for reducing postoperative anemia and the need for blood transfusions. The aim of this study was to evaluate the CATSmart Continuous Autotransfusion System wash program performance with small (200 or 700 mL) and large volumes (1,000 mL) of shed blood and to determine non-inferiority of the CATSmart to the C.A.T.Splus system. Human whole blood was collected in citrate phosphate dextrose, diluted, and divided into two aliquots to be processed as a pair using the C.A.T.Splus and CATSmart systems with their corresponding wash programs: low-volume, high quality/smart, or emergency wash. Final packed red cell product was analyzed for red blood cell (RBC), white blood cell, and platelet counts; hemoglobin; hemolysis; RBC recovery rates; and elimination of albumin, total protein, and potassium. The mean hematocrit (HCT) after processing with CATSmart and C.A.T.Splus systems were 59.63% and 57.71%, respectively. The calculated overall RBC recovery rates on the CATSmart and C.A.T.Splus systems were 85.41% and 84.99%, respectively. Elimination of albumin (97.5%, 98.0%), total proteins (97.1%, 97.5%), and potassium (92.1%, 91.9%) were also calculated for the CATSmart and C.A.T.Splus systems. The CATSmart and C.A.T.Splus systems both provided a high-quality product in terms of HCT, protein elimination, and hemolysis rates across the range of tested shed blood volumes and all wash programs. The study was able to confirm the CATSmart is non-inferior to the C.A.T.Splus system. PMID:28638159

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.

Interleukin-6 Directly Impairs the Erythroid Development of Human TF-1 Erythroleukemic Cells

PubMed Central

McCranor, Bryan J.; Kim, Min Jung; Cruz, Nicole M.; Xue, Qian-Li; Berger, Alan E.; Walston, Jeremy D.; Civin, Curt I.; Roy, Cindy N.

2013-01-01

Anemia of inflammation or chronic disease is a highly prevalent form of anemia. The inflammatory cytokine interleukin-6 (IL-6) negatively correlates with hemoglobin concentration in many disease states. The IL-6-hepcidin antimicrobial peptide axis promotes iron-restricted anemia; however the full role of IL-6 in anemia of inflammation is not well-defined. We previously reported that chronic inflammation had a negative impact on maturation of erythroid progenitors in a mouse model. We hypothesized that IL-6 may be responsible for impaired erythropoiesis, independent of iron restriction. To test the hypothesis we utilized the human erythroleukemia TF-1 cell line to model erythroid maturation and exposed them to varying doses of IL-6 over six days. At 10 ng/ml, IL-6 significantly repressed erythropoietin-dependent TF-1 erythroid maturation. While IL-6 did not decrease the expression of genes associated with hemoglobin synthesis, we observed impaired hemoglobin synthesis as demonstrated by decreased benzidine staining. We also observed that IL-6 down regulated expression of the gene SLC4a1 which is expressed late in erythropoiesis. Those findings suggested that IL-6-dependent inhibition of hemoglobin synthesis might occur. We investigated the impact of IL-6 on mitochondria. IL-6 decreased the mitochondrial membrane potential at all treatment doses, and significantly decreased mitochondrial mass at the highest dose. Our studies indicate that IL-6 may impair mitochondrial function in maturing erythroid cells resulting in impaired hemoglobin production and erythroid maturation. Our findings may indicate a novel pathway of action for IL-6 in the anemia of inflammation, and draw attention to the potential for new therapeutic targets that affect late erythroid development. PMID:24119518

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

PubMed

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

2013-01-01

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

Statistical methods for estimating normal blood chemistry ranges and variance in rainbow trout (Salmo gairdneri), Shasta Strain

USGS Publications Warehouse

Wedemeyer, Gary A.; Nelson, Nancy C.

1975-01-01

Gaussian and nonparametric (percentile estimate and tolerance interval) statistical methods were used to estimate normal ranges for blood chemistry (bicarbonate, bilirubin, calcium, hematocrit, hemoglobin, magnesium, mean cell hemoglobin concentration, osmolality, inorganic phosphorus, and pH for juvenile rainbow (Salmo gairdneri, Shasta strain) trout held under defined environmental conditions. The percentile estimate and Gaussian methods gave similar normal ranges, whereas the tolerance interval method gave consistently wider ranges for all blood variables except hemoglobin. If the underlying frequency distribution is unknown, the percentile estimate procedure would be the method of choice.

Hemoglobin Regulates the Metabolic, Synthetic, Detoxification, and Biotransformation Functions of Hepatoma Cells Cultured in a Hollow Fiber Bioreactor

PubMed Central

Chen, Guo

2010-01-01

Hepatic hollow fiber (HF) bioreactors constitute one type of extracorporeal bioartificial liver assist device (BLAD). Ideally, cultured hepatocytes in a BLAD should closely mimic the in vivo oxygenation environment of the liver sinusoid to yield a device with optimal performance. However, most BLADs, including hepatic HF bioreactors, suffer from O2 limited transport toward cultured hepatocytes, which reduces their performance. We hypothesize that supplementation of hemoglobin-based O2 carriers into the circulating cell culture medium of hepatic HF bioreactors is a feasible and effective strategy to improve bioreactor oxygenation and performance. We examined the effect of bovine hemoglobin (BvHb) supplementation (15 g/L) in the circulating cell culture medium of hepatic HF bioreactors on hepatocyte proliferation, metabolism, and varied liver functions, including biosynthesis, detoxification, and biotransformation. It was observed that BvHb supplementation supported the maintenance of a higher cell mass in the extracapillary space, improved hepatocyte metabolic efficiency (i.e., hepatocytes consumed much less glucose), improved hepatocyte capacity for drug metabolism, and conserved both albumin synthesis and ammonia detoxification functions compared to controls (no BvHb supplementation) under the same experimental conditions. PMID:20528678

An Iron-Regulated Autolysin Remodels the Cell Wall To Facilitate Heme Acquisition in Staphylococcus lugdunensis

PubMed Central

Farrand, Allison J.; Haley, Kathryn P.; Lareau, Nichole M.; Heilbronner, Simon; McLean, John A.; Foster, Timothy

2015-01-01

Bacteria alter their cell surface in response to changing environments, including those encountered upon invasion of a host during infection. One alteration that occurs in several Gram-positive pathogens is the presentation of cell wall-anchored components of the iron-regulated surface determinant (Isd) system, which extracts heme from host hemoglobin to fulfill the bacterial requirement for iron. Staphylococcus lugdunensis, an opportunistic pathogen that causes infective endocarditis, encodes an Isd system. Unique among the known Isd systems, S. lugdunensis contains a gene encoding a putative autolysin located adjacent to the Isd operon. To elucidate the function of this putative autolysin, here named IsdP, we investigated its contribution to Isd protein localization and hemoglobin-dependent iron acquisition. S. lugdunensis IsdP was found to be iron regulated and cotranscribed with the Isd operon. IsdP is a specialized peptidoglycan hydrolase that cleaves the stem peptide and pentaglycine crossbridge of the cell wall and alters processing and anchoring of a major Isd system component, IsdC. Perturbation of IsdC localization due to isdP inactivation results in a hemoglobin utilization growth defect. These studies establish IsdP as an autolysin that functions in heme acquisition and describe a role for IsdP in cell wall reorganization to accommodate nutrient uptake systems during infection. PMID:26123800

Beta Thalassemia (For Parents)

MedlinePlus

... July 2015 More on this topic for: Parents Kids Teens Blood Transfusions Iron Iron-Deficiency Anemia Blood Test: Hemoglobin Electrophoresis Sickle Cell Disease Alpha Thalassemia Anemia Word! Anemia About Anemia Stem Cell Transplants Blood Transfusions Anemia Sickle Cell Disease ...

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.

Mixtures of tense and relaxed state polymerized human hemoglobin regulate oxygen affinity and tissue construct oxygenation

PubMed Central

Belcher, Donald Andrew; Banerjee, Uddyalok; Baehr, Christopher Michael; Richardson, Kristopher Emil; Cabrales, Pedro; Berthiaume, François

2017-01-01

Pure tense (T) and relaxed (R) quaternary state polymerized human hemoglobins (PolyhHbs) were synthesized and their biophysical properties characterized, along with mixtures of T- and R-state PolyhHbs. It was observed that the oxygen affinity of PolyhHb mixtures varied linearly with T-state mole fraction. Computational analysis of PolyhHb facilitated oxygenation of a single fiber in a hepatic hollow fiber (HF) bioreactor was performed to evaluate the oxygenation potential of T- and R-state PolyhHb mixtures. PolyhHb mixtures with T-state mole fractions greater than 50% resulted in hypoxic and hyperoxic zones occupying less than 5% of the total extra capillary space (ECS). Under these conditions, the ratio of the pericentral volume to the perivenous volume in the ECS doubled as the T-state mole fraction increased from 50 to 100%. These results show the effect of varying the T/R-state PolyhHb mole fraction on oxygenation of tissue-engineered constructs and their potential to oxygenate tissues. PMID:29020036

NIR time domain diffuse optical tomography experiments on human forearm

NASA Astrophysics Data System (ADS)

Zhao, Huijuan; Gao, Feng; Tanikawa, Yukari; Homma, Kazuhiro; Yamada, Yukio

2003-07-01

To date, the applications of near infrared (NIR) diffusion optical tomography (DOT) are mostly focused on the potential of imaging woman breast, human head hemodynamics and neonatal head. For the neonates, who are suffered from ischaemia or hemorrhages in brain, bedside monitoring of the cerebral perfusion situation, e.g., the blood oxygen saturation and blood volume, is necessary for avoiding permanent injure. NIR DOT is on the promising tools because it is noninvasive, smaller in size, and moveable. Prior to achieving the ultimate goal of imaging infant brain and woman breast using DOT, in this paper, the developed methodologies are justified by imaging in vivo human forearms. The absolute absorption- and scattering-coefficient images revealed the inner structure of the forearm and the bones were clearly distinguished from the muscle. The differential images showed the changes in oxy-hemoglobin, deoxy-hemoglobin and blood volume during the hand-gripping exercises, which are consistent with the physiological process reported on literatures.

Can Eosinophil Count, Platelet Count, and Mean Platelet Volume Be a Positive Predictive Factor in Penile Arteriogenic Erectile Dysfunction Etiopathogenesis?

PubMed Central

Sönmez, Mehmet Giray; Göğer, Yunus Emre; Sönmez, Leyla Öztürk; Aydın, Arif; Balasar, Mehmet; Kara, Cengiz

2016-01-01

Blood count parameters of patients referring with erectile dysfunction (ED) were examined in this study and it was investigated whether eosinophil count (EC), platelet count (PC), and mean platelet volume values among the suspected predictive parameters which may play a role in especially penile arteriogenic ED etiopathogenesis had a contribution on pathogenesis. Patients referring with ED complaint were evaluated. Depending on the medical story, ED degree was determined by measuring International Index of Erectile Function. Penile Doppler ultrasonography was taken in patients suspected to have vasculogenic ED. According to penile Doppler ultrasonography result, patients with arterial deficiency were included in the penile arteriogenic ED group and the patients with normal results were included in the nonvasculogenic ED group. A total of 36 patients participated in the study from the penile arteriogenic ED group and 32 patients from the nonvasculogenic ED group. Compared with the nonvasculogenic ED group, the penile arteriogenic ED group’s low International Index of Erectile Function score, high EC, mean platelet volume and PC values were detected to be statistically significant (p < .001, p = .021, p = .018, p = .034, respectively). No statistically significant difference was observed among the two groups when age, white blood cells, red blood cells, and hemoglobin values were considered. Pansystolic volume velocities were detected as statistically significantly low compared with the nonvasculogenic ED group in the measurements made in 5th, 10th, 15th, and 20th minutes on the right and left sides in the penile arteriogenic ED group. High MPV value and PC is a significant predictive factor for penile arteriogenic ED and vasculogenic ED and high EC is specifically predictive of arteriogenic ED. PMID:27895254

True Anemia-Red Blood Cell Volume Deficit-in Heart Failure: A Systematic Review.

PubMed

Montero, David; Lundby, Carsten; Ruschitzka, Frank; Flammer, Andreas J

2017-05-01

Anemia in heart failure (HF) is commonly diagnosed according to hemoglobin concentration [Hb], hence may be the result of hemodilution or true red blood cell volume (RBCV) deficit. Whether true (nonhemodilutional) anemia in HF can or cannot be generally inferred by [Hb] measurements and clinical correlates remains unclear. The purpose of this study was to systematically review the literature and investigate the status and correlates of RBCV in patients with HF. MEDLINE, Scopus, and Web of Science were searched since their inceptions until April 2016 for articles directly reporting or allowing the calculation of intravascular volumes (RBCV, plasma volume) in patients with HF according to the International Council for Standardization in Hematology. Eighteen studies were included after systematic review, comprising a total of 368 patients with HF (limits for mean age=49-80 years, sex=0%-92% females, left ventricular ejection fraction=26%-61%). Mean RBCV was reduced (limits=67%-88% of normal) in all studies including HF patients with anemia (low [Hb]) (7 studies, n=127), whereas only 2 of 10 studies in nonanemic patients with HF presented lower than normal mean RBCV (90% and 96%). In metaregression analyses, RBCV was positively associated with [Hb] ( B =6.10, SE=1.44) and negatively associated with age ( B =-1.14, SE=0.23), % females ( B =-0.38, SE=0.04), left ventricular ejection fraction ( B =-0.81, SE=0.20), and body mass index ( B =-3.55, SE=0.46; P <0.001). Presence or absence of true anemia in patients with HF as determined by RBCV status mainly concurs with diagnosis based on [Hb] and presents negative relationships with age, female sex, left ventricular ejection fraction, and body mass index. © 2017 American Heart Association, Inc.

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

Key endothelial cell angiogenic mechanisms are stimulated by the circulating milieu in sickle cell disease and attenuated by hydroxyurea

PubMed Central

Lopes, Flavia C. M.; Traina, Fabiola; Almeida, Camila B.; Leonardo, Flavia C.; Franco-Penteado, Carla F.; Garrido, Vanessa T.; Colella, Marina P.; Soares, Raquel; Olalla-Saad, Sara T.; Costa, Fernando F.; Conran, Nicola

2015-01-01

As hypoxia-induced inflammatory angiogenesis may contribute to the manifestations of sickle cell disease, we compared the angiogenic molecular profiles of plasma from sickle cell disease individuals and correlated these with in vitro endothelial cell-mediated angiogenesis-stimulating activity and in vivo neovascularization. Bioplex demonstrated that plasma from patients with steady-state sickle cell anemia contained elevated concentrations of pro-angiogenic factors (angiopoietin-1, basic fibroblast growth factor, vascular endothelial growth factor, vascular endothelial growth factor-D and placental growth factor) and displayed potent pro-angiogenic activity, significantly increasing endothelial cell proliferation, migration and capillary-like structure formation. In vivo neovascularization of Matrigel plugs was significantly greater in sickle cell disease mice than in non-sickle cell disease mice, consistent with an up-regulation of angiogenesis in the disease. In plasma from patients with hemoglobin SC disease without proliferative retinopathy, anti-angiogenic endostatin and thrombospondin-2 were significantly elevated. In contrast, plasma from hemoglobin SC individuals with proliferative retinopathy had a pro-angiogenic profile and more significant effects on endothelial cell proliferation and capillary formation than plasma from patients without retinopathy. Hydroxyurea therapy was associated with significant reductions in plasma angiogenic factors and inhibition of endothelial cell-mediated angiogenic mechanisms and neovascularization. Thus, individuals with sickle cell anemia or hemoglobin SC disease with retinopathy present a highly angiogenic circulating milieu, capable of stimulating key endothelial cell-mediated angiogenic mechanisms. Combination anti-angiogenic therapy to prevent the progression of unregulated neovascularization and associated manifestations in sickle cell disease, such as pulmonary hypertension, may be indicated; furthermore, the benefits and drawbacks of the potent anti-angiogenic effects of hydroxyurea should be clarified. PMID:25769545

Identification of a Novel Class of Covalent Modifiers of Hemoglobin as Potential Antisickling Agents

PubMed Central

Omar, A. M.; Mahran, M. A.; Ghatge, M. S.; Chowdhury, N.; Bamane, F. H. A.; El-Araby, M. E.; Abdulmalik, O.; Safo, M. K.

2015-01-01

Aromatic aldehydes and ethacrynic acid (ECA) exhibit antipolymerization properties that are beneficial for sickle cell disease therapy. Based on ECA pharmacophore and its atomic interaction with hemoglobin, we designed and synthesized several compounds--designated as KAUS (imidazolylacryloyl derivatives)--that we hypothesized would bind covalently to βCys93 of hemoglobin and inhibit sickling. The compounds surprisingly showed weak allosteric and antisickling properties. X-ray studies of hemoglobin in complex with representative KAUS compounds revealed an unanticipated mode of Michael addition reaction between the β-unsaturated carbon and the N-terminal αVal1 nitrogen at the α-cleft of hemoglobin, with no observable interaction with βCys93. Interestingly, the compounds exhibited almost no reactivity with the free amino acids, L-Val, L-His and L-Lys, however showed some reactivity with both glutathione and L-Cys. Our findings provide a molecular level explanation to the compounds biological activities and an important framework for targeted modifications that would yield novel potent antisickling agents. PMID:25974708

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

Efficacy of supplementation in filipino children.

PubMed

Tayao, Charisse Marie S

2015-01-01

At present, in the absence of an anemia prevention and screening program in Barangay Vasra, this will aid in the formation of programs that would teach about this health related issue, with an intervention that could be used efficiently by the health workers at the non-government organization run center. The aim of the following study is to establish the efficacy of iron supplementation alone versus iron and ascorbic acid supplementation in improving the hemoglobin (Hgb), hematocrit (Hct), reticulocyte count and red cell indices of anemic undernourished children 5-10 years of age at Lingap Center, Barangay Vasra, Quezon City. Anemic undernourished male and female children 5-10 years of age enrolled in the Supplementary Feeding Program of Lingap Center, Barangay Vasra, Quezon City. Prospective, experimental trial comparing two interventions-iron supplementation alone versus iron and ascorbic acid supplementation. A total of 25 children participated in this study, with a majority being female at 52% (13/25) of the total. Those who received iron supplementation alone for 6 months, while there were 50% (6/12) of either sex, whereas subjects who took iron and ascorbic acid supplementation for 6 months were predominantly female at 53.85% (7/13). Data obtained before and after iron supplementation alone revealed that there was an increase among the levels of Hgb, Hct, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC) and reticulocyte count, with the rise statistically significant. Hematological values gained before and after iron and ascorbic acid supplementation uncovered that there was an augmentation among the levels of Hct, MCV, MCH, MCHC and reticulocyte count, with the improvement statistically significant. Encompassing both interventions, the differences in findings were statistically significant in red blood cell (RBC) count, with the level progression statistically significant. Overall, the results were statistically significant in terms of RBC count alone. Therefore, this study demonstrated that compliance with intake of supplementation is a factor in improving the hematological parameters of these subjects. To address iron deficiency anemia, a similar endeavor may establish a system of support in Lingap Center to ensure the screening and therapeutic management of this population.

Efficacy of Supplementation in Filipino Children

PubMed Central

Tayao, Charisse Marie S.

2015-01-01

Introduction: At present, in the absence of an anemia prevention and screening program in Barangay Vasra, this will aid in the formation of programs that would teach about this health related issue, with an intervention that could be used efficiently by the health workers at the non-government organization run center. Objective: The aim of the following study is to establish the efficacy of iron supplementation alone versus iron and ascorbic acid supplementation in improving the hemoglobin (Hgb), hematocrit (Hct), reticulocyte count and red cell indices of anemic undernourished children 5-10 years of age at Lingap Center, Barangay Vasra, Quezon City. Methodology: Anemic undernourished male and female children 5-10 years of age enrolled in the Supplementary Feeding Program of Lingap Center, Barangay Vasra, Quezon City. Study Design: Prospective, experimental trial comparing two interventions-iron supplementation alone versus iron and ascorbic acid supplementation. Results: A total of 25 children participated in this study, with a majority being female at 52% (13/25) of the total. Those who received iron supplementation alone for 6 months, while there were 50% (6/12) of either sex, whereas subjects who took iron and ascorbic acid supplementation for 6 months were predominantly female at 53.85% (7/13). Data obtained before and after iron supplementation alone revealed that there was an increase among the levels of Hgb, Hct, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC) and reticulocyte count, with the rise statistically significant. Hematological values gained before and after iron and ascorbic acid supplementation uncovered that there was an augmentation among the levels of Hct, MCV, MCH, MCHC and reticulocyte count, with the improvement statistically significant. Encompassing both interventions, the differences in findings were statistically significant in red blood cell (RBC) count, with the level progression statistically significant. Conclusion: Overall, the results were statistically significant in terms of RBC count alone. Therefore, this study demonstrated that compliance with intake of supplementation is a factor in improving the hematological parameters of these subjects. To address iron deficiency anemia, a similar endeavor may establish a system of support in Lingap Center to ensure the screening and therapeutic management of this population. PMID:25810994

Time-resolved optical spectroscopic quantification of red blood cell damage caused by cardiovascular devices

NASA Astrophysics Data System (ADS)

Sakota, D.; Sakamoto, R.; Sobajima, H.; Yokoyama, N.; Yokoyama, Y.; Waguri, S.; Ohuchi, K.; Takatani, S.

2008-02-01

Cardiovascular devices such as heart-lung machine generate un-physiological level of shear stress to damage red blood cells, leading to hemolysis. The diagnostic techniques of cell damages, however, have not yet been established. In this study, the time-resolved optical spectroscopy was applied to quantify red blood cell (RBC) damages caused by the extracorporeal circulation system. Experimentally, the fresh porcine blood was subjected to varying degrees of shear stress in the rotary blood pump, followed with measurement of the time-resolved transmission characteristics using the pico-second pulses at 651 nm. The propagated optical energy through the blood specimen was detected using a streak camera. The data were analyzed in terms of the mean cell volume (MCV) and mean cell hemoglobin concentration (MCHC) measured separately versus the energy and propagation time of the light pulses. The results showed that as the circulation time increased, the MCV increased with decrease in MCHC. It was speculated that the older RBCs with smaller size and fragile membrane properties had been selectively destroyed by the shear stress. The time-resolved optical spectroscopy is a useful technique in quantifying the RBCs' damages by measuring the energy and propagation time of the ultra-short light pulses through the blood.

Optical oximetry of volume-oscillating vascular compartments: contributions from oscillatory blood flow

NASA Astrophysics Data System (ADS)

Kainerstorfer, Jana M.; Sassaroli, Angelo; Fantini, Sergio

2016-10-01

We present a quantitative analysis of dynamic diffuse optical measurements to obtain oxygen saturation of hemoglobin in volume oscillating compartments. We used a phasor representation of oscillatory hemodynamics at the heart rate and respiration frequency to separate the oscillations of tissue concentrations of oxyhemoglobin (O) and deoxyhemoglobin (D) into components due to blood volume (subscript V) and blood flow (subscript F): O=OV+OF, D=DV+DF. This is achieved by setting the phase angle Arg(OF)-Arg(O), which can be estimated by a hemodynamic model that we recently developed. We found this angle to be -72 deg for the cardiac pulsation at 1 Hz, and -7 deg for paced breathing at 0.1 Hz. Setting this angle, we can obtain the oxygen saturation of hemoglobin of the volume-oscillating vascular compartment, SV=|OV|/(|OV|+|DV|). We demonstrate this approach with cerebral near-infrared spectroscopy measurements on healthy volunteers at rest (n=4) and during 0.1 Hz paced breathing (n=3) with a 24-channel system. Rest data at the cardiac frequency were used to calculate the arterial saturation, S(a); over all subjects and channels, we found ==0.96±0.02. In the case of paced breathing, we found =0.66±0.14, which reflects venous-dominated hemodynamics at the respiratory frequency.

Light Scattering and Absorption Studies of Sickle Cell Hemoglobin

NASA Astrophysics Data System (ADS)

Kim-Shapiro, Daniel

1997-11-01

The use of physical techniques has been very important in understanding the pathophysiology of sickle cell disease. In particular, light scattering and absorption studies have been used to measure the kinetics of sickle cell hemoglobin polymerization and depolymerization (melting). The theory of sickle cell polymerization that has been derived and tested by these methods has not only led to an increased understanding of the pathophysiology of the disease but has also led to improved treatment strategies. Sickle cell disease effects about 1 out of 600 people of African descent born in the United States. The disease is caused by a mutant form of hemoglobin (the oxygen transporting molecule in the blood), hemoglobin S (HbS), which differs from normal adult hemoglobin by the substitution of a single amino acid for another. The polymerization of HbS, which occurs under conditions of low oxygen pressure, causes distortion and increased rigidity of the sickle red blood cell that leads to blockage of the capillaries and a host of resulting complications. The disease is associated with tissue damage, severe painful crises and a high degree of mortality. Light scattering studies of purified HbS and whole cells (conducted by F.A. Ferrone, J. Hofrichter, W.A. Eaton, and their associates) have been used to determine the mechanism of HbS polymerization. Polymerization will generally not occur when the hemoglobin is in an oxygen-rich environment. The question is, when HbS is rapidly deoxygenated (as it is when going from the lungs to the tissues) what is the kinetics of polymerization? Photolysis methods were used to rapidly deoxygenate HbS and light scattering was used as a function of time to measure the kinetics of polymerization. Polarized light scattering may be a more effective way to measure polymer content than total intensity light scattering. It was found that no polymerization occurs during a period of time called the delay time and subsequent polymerization occurs exponentially. The length of this delay time depends on the concentration of deoxy-HbS. The kinetics of polymerization was described by a novel double nucleation mechanism. These light scattering studies led to the understanding that many cells could travel through oxygen deficient tissue without sickling due to the delay time in polymerization. Some treatment strategies involve prolonging the delay time. Less work has been done in trying to understand polymer melting. Such investigations are important in order to determine whether polymers that reach the lungs melt before they enter the oxygen deficient tissues. I have initially addressed this problem by exploring the kinetics of oxygen binding to the polymers. These studies were conducted using time-resolved linear dichroism following laser photolysis. Preliminary studies in my laboratory indicate that polymer melting is slow enough to be an important consideration in understanding sickle cell disease. One of the most common therapies for sickle cell disease that is currently used involves administering the drug, hydroxyurea. The mechanism by which this drug benefits patients is not fully understood. One of its mechanisms (as determined by light scattering and absorption studies) involves increasing the delay time for polymerization.

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.

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

PubMed

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

2011-01-01

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

Pathophysiologically based drug treatment of sickle cell disease.

PubMed

Steinberg, Martin H

2006-04-01

Sickle cell disease is a systemic disorder that is caused by a mutation (Glu6Val) in the gene that encodes beta globin. The sickle hemoglobin molecule (HbS) is a tetramer of two alpha-globin chains and two sickle beta-globin chains, and has the tendency to polymerize when deoxygenated. HbS facilitates abnormal interactions between the sickle erythrocyte and leukocytes and endothelial cells, which trigger a complex pathobiology. This multifaceted pathophysiology provides the opportunity to interrupt the disease at multiple sites, including polymerization of HbS, erythrocyte density and cell-cell interactions. For example, it is possible to induce higher concentrations of fetal hemoglobin, which disrupts the pathology-initiating step of HbS polymerization. Furthermore, it is possible to improve the hydration of sickle erythrocytes and it might be feasible to counteract the endothelial, inflammatory and oxidative abnormalities of sickle cell disease. A therapeutic approach that targets several sites of pathobiology might be most promising.

Is Erythrocyte Protoporphyrin a Better Single Screening Test for Iron Deficiency Compared to Hemoglobin or Mean Cell Volume in Children and Women?

PubMed

Mei, Zuguo; Flores-Ayala, Rafael C; Grummer-Strawn, Laurence M; Brittenham, Gary M

2017-05-31

Hemoglobin (Hb), mean cell volume (MCV), and erythrocyte protoporphyrin (EP) are commonly used to screen for iron deficiency (ID), but systematic evaluation of the sensitivity and specificity of these tests is limited. The objective of this study is to determine the sensitivity and specificity of Hb, MCV, and EP measurements in screening for ID in preschool children, non-pregnant women 15-49 years of age, and pregnant women. Data from the National Health and Nutrition Examination Surveys (NHANES) (NHANES 2003-2006: n = 861, children three to five years of age; n = 3112, non-pregnant women 15 to 49 years of age. NHANES 1999-2006: n = 1150, pregnant women) were examined for this purpose. Children or women with blood lead ≥10 µg/dL or C-reactive protein (CRP) >5.0 mg/L were excluded. ID was defined as total body iron stores <0 mg/kg body weight, calculated from the ratio of soluble transferrin receptor (sTfR) to serum ferritin (SF). The receiver operating characteristic (ROC) curve was used to characterize the sensitivity and specificity of Hb, MCV, and EP measurements in screening for ID. In detecting ID in children three to five years of age, EP (Area under the Curve (AUC) 0.80) was superior to Hb (AUC 0.62) ( p < 0.01) but not statistically different from MCV (AUC 0.73). In women, EP and Hb were comparable (non-pregnant AUC 0.86 and 0.84, respectively; pregnant 0.77 and 0.74, respectively), and both were better than MCV (non-pregnant AUC 0.80; pregnant 0.70) ( p < 0.01). We concluded that the sensitivity and specificity of EP in screening for ID were consistently superior to or at least as effective as those of Hb and MCV in each population examined. For children three to five years of age, EP screening for ID was significantly better than Hb and similar to MCV. For both non-pregnant and pregnant women, the performance of EP and Hb were comparable; both were significantly superior to MCV.

Hematologic and serum biochemical reference intervals for Florida panthers.

USGS Publications Warehouse

Dunbar, M.R.; Nol, P.; Linda, S.B.

1997-01-01

Ninety-four blood samples were collected from 48 (29 males and 19 females) free-ranging Florida panthers (Felis concolor coryi) captured in southern Florida (USA) from 1983 to 1994 for routine hematological and serum biochemical analysis. Florida panthers in the northern portion of their range had significantly higher red blood cell (mean +/- SD = 7.923 x 10(6) +/- 0.854 x 10(6)/microliter), hemoglobin (12.53 +/- 1.66 g/dl), and packed cell volume (36.97 +/- 4.27%) values compared to those of panthers localized in more southern parts of Florida (7.148 x 10(6) +/- 1.045 x 10(6)/microliter, 11.60 +/- 1.62 g/dl, and 34.82 +/- 5.99%, respectively). Adults had significantly higher mean serum total protein (7.50 +/- 0.59 g/dl) and packed cell volume (36.90 +/- 4.97%) values than juveniles (6.88 +/- 0.49 g/dl and 34.54 +/- 5.30%). However, mean serum albumin concentrations were significantly higher in juveniles (3.80 +/- 0.26 g/dl) when compared to adult values (3.58 +/- 0.26 g/dl). Mean serum calcium concentrations were significantly higher in juveniles (10.33 +/- 0.39 mg/dl) than in adults (9.66 +/- 0.45 mg/dl). Additionally, mean serum iron concentrations were significantly higher in those panthers of intergrade genetic stock compared to values in those of authentic genetic stock (105.6 +/- 72.1 micrograms/dl versus 59.3 +/- 19.7 micrograms/dl, respectively).

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.

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.

Strategies for Small Volume Resuscitation: Hyperosmotic-Hyperoncotic Solutions, Hemoglobin Based Oxygen Carriers and Closed-Loop Resuscitation

NASA Technical Reports Server (NTRS)

Kramer, George C.; Wade, Charles E.; Dubick, Michael A.; Atkins, James L.

2004-01-01

Introduction: Logistic constraints on combat casualty care preclude traditional resuscitation strategies which can require volumes and weights 3 fold or greater than hemorrhaged volume. We present a review of quantitative analyses of clinical and animal data on small volume strategies using 1) hypertonic-hyperosmotic solutions (HHS); 2) hemoglobin based oxygen carriers (HBOCs) and 3) closed-loop infusion regimens.Methods and Results: Literature searches and recent queries to industry and academic researchers have allowed us to evaluate the record of 81 human HHS studies (12 trauma trials), 19 human HBOCs studies (3trauma trials) and two clinical studies of closed-loop resuscitation.There are several hundreds animal studies and at least 82 clinical trials and reports evaluating small volume7.2%-7.5% hypertonic saline (HS) most often combined with colloids, e.g., dextran (HSD) or hetastarch(HSS). HSD and HSS data has been published for 1,108 and 392 patients, respectively. Human studies have documented volume sparing and hemodynamic improvements. Meta-analyses suggest improved survival for hypotensive trauma patients treated with HSD with significant reductions in mortality found for patients with blood pressure < 70 mmHg, head trauma, and penetrating injury requiring surgery. HSD and HSS have received regulatory approval in 14 and 3 countries, respectively, with 81,000+ units sold. The primary reported use was head injury and trauma resuscitation. Complications and reported adverse events are surprisingly rare and not significantly different from other solutions.HBOCs are potent volume expanders in addition to oxygen carriers with volume expansion greater than standard colloids. Several investigators have evaluated small volume hyperoncotic HBOCs or HS-HBOC formulations for hypotensive and normotensive resuscitation in animals. A consistent finding in resuscitation with HBOCs is depressed cardiac output. There is some evidence that HBOCs more efficiently unload oxygen from plasma hemoglobin as well as facilitate RBC unloading. We analyzed one volunteer study, 15 intraoperative trials, and 3 trauma studies using HBOCs. Perioperative studies generally suggest ability to deliver oxygen, but one trauma trial using HBOCs (HemAssist) for treatment of trauma resulted in a dramatic increase in mortality, while an intraoperative trauma study using Polyheme demonstrated reductions in blood use and lower mortality compared to historic controls of patients refusing blood. Transfusion reductions with HBOC use have been modest. Two HBOCs (Hemopure and Polyheme) are now in new or planned large-scale multicenter prehospital trials of trauma treatment. A new implementation of small volume resuscitation is closed-loop resuscitation (CLR), which employs microprocessors to titrate just enough fluid to reach a physiologic target . Animal studies suggest less risk of rebleeding in uncontrolled hemorrhage and a reduction in fluid needs with CLR. The first clinical application of CLR was treatment of burn shock and the US Army. Conclusions: Independently sponsored civilian trauma trials and clinical evaluations in operational combat conditions of different small volume strategies are warranted.

Developmental Function in Toddlers With Sickle Cell Anemia

PubMed Central

Elkin, T. David; Brown, R. Clark; Glass, Penny; Rana, Sohail; Casella, James F.; Kalpatthi, Ram V.; Pavlakis, Steven; Mi, Zhibao; Wang, Winfred C.

2013-01-01

BACKGROUND: Neurocognitive impairment occurs in children and adults with sickle cell anemia, but little is known about neurodevelopment in very young children. We examined the neurodevelopmental status of infants participating in the Pediatric Hydroxyurea Phase III Clinical Trial (Baby Hug) to determine relationships with age, cerebral blood flow velocity, and hemoglobin concentration. METHODS: Standardized measures of infant neurodevelopment were administered to 193 infants with hemoglobin SS or hemoglobin S-β0 thalassemia between 7 and 18 months of age at the time of their baseline evaluation. Associations between neurodevelopmental scores and age, family income, parent education, hemoglobin concentration, and transcranial Doppler velocity were examined. RESULTS: Mean functioning on the baseline neurodevelopment scales was in the average range. There were no mental development scores <70 (impaired); 22 children had scores in the clinically significant range, 11 with impaired psychomotor scores and 11 with problematic behavior rating scores. Significantly poorer performance was observed with older age at baseline. Behavior rating scores were an average of 2.82 percentile points lower per month of age, with similar patterns observed with parent report using adaptive behavior scales. Parent-reported functional abilities and hemoglobin were negatively associated with higher transcranial Doppler velocities. CONCLUSIONS: Whereas overall functioning was in the normal range, behavioral and adaptive function was poorer with older age, even in this very young group of children. Explanatory mechanisms for this association between poorer developmental function and older age need to be identified. PMID:23296434

Beyond the Golden Hours: Caring for Septic Patients After the Initial Resuscitation.

PubMed

Gelinas, Jean P; Walley, Keith R

2016-06-01

Recognition and management of agitation, delirium, and pain are key areas. Reduced use of sedatives is an important measure that must be coupled with increased patient engagement, mobilization, and exercise. Use of low tidal volumes and low mean airway pressures during mechanical ventilation is helpful. A key hemodynamic principle following early aggressive volume resuscitation is subsequent careful assessment to avoid unnecessary additional volume administration and adverse consequences of frank volume overload. Substantial evidence now supports a lower hemoglobin transfusion threshold of 7 g/dL. A rush to initiate enteral or parenteral feeds is not clearly supported by the current evidence. Copyright © 2016 Elsevier Inc. All rights reserved.

Low volume tubes are not effective to reduce the rate of hemolyzed specimens from the emergency department.

PubMed

Lippi, Giuseppe; Bonelli, Patrizia; Graiani, Virna; Caleffi, Catia; Cervellin, Gianfranco

2014-02-01

Spurious hemolysis is the leading source of nonconformities that can be recorded in diagnostic samples, especially those collected in the emergency department (ED). The aim of this study was to assess whether the shift from regular to low volume blood collection tubes may reduce the rate of hemolysis in a large urban ED, where approximately 80% of blood collections are performed through catheters. In a former 5-month period, blood collection in the ED was performed using 5.0mL (13×100mm) plastic serum tubes, which were then completely replaced with 3.5mL (13×75mm) plastic serum tubes for another period of 5months. The rate of hemolyzed specimens (i.e., those containing a cell-free hemoglobin ≥0.5gL) collected in the two periods was compared by Fisher exact test. The rate of hemolyzed specimens received from the ED increased from 3.5% using 5.0mL plastic serum tubes to 5.2% after introduction of 3.5mL plastic serum tubes (p<0.001). The use of low volume tubes was not effective to decrease the hemolysis rate in a large urban ED. Copyright © 2013 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

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.

Prefrontal Dysfunction in Attention-Deficit/Hyperactivity Disorder as Measured by Near-Infrared Spectroscopy

ERIC Educational Resources Information Center

Negoro, Hideki; Sawada, Masayuki; Iida, Junzo; Ota, Toyosaku; Tanaka, Shohei; Kishimoto, Toshifumi

2010-01-01

Recent developments in near-infrared spectroscopy (NIRS) have enabled non-invasive clarification of brain functions in psychiatric disorders with measurement of hemoglobin concentrations as cerebral blood volume. Twenty medication-naive children with attention-deficit/hyperactivity disorder (ADHD) and 20 age- and sex-matched healthy control…

Hemosomegenesis and hemoglobin biosynthesis in vertebrates.

PubMed

Brunner Júnior, A; de Rizzo, E; Morena, D D; Cianciarullo, A M; Jared, C; Morena, P

1992-08-01

1. Ultrastructural observations on maturing rabbit embryo erythroid cells led to the finding of hemoglobinized organelles distinguishable from mitochondria due to their highly dense matrix, two or three longitudinally arranged double lamellae, and smaller diameters. Intraorganellar 50-60 A particles identical to those contained in the hemoglobinized cytoplasm were found. 2. Their hemoglobin (Hb) content was demonstrated by electrophoresis of the concentrated supernatant from the isolated, washed, and osmotically lysed organellar fraction. We have proposed that these organelles are the sites for heme integration into the globin (G) polypeptide chains and subunits assembly. The term hemosome has been suggested for such entities. 3. This hypothesis has been sustained by several analytical and experimental works based on the postulation that hemosomes should be found at higher frequencies where the Hb biosynthesis rate is more intensive, or where the induction of this biosynthesis is always dependent on the formation of hemosomes. 4. Maturing erythroid cells of the circulating embryo blood contain hemosomes in higher frequency than in liver erythroid cells, coinciding with the higher Hb biosynthesis rate in peripheral blood than in the liver. In bleeding anemia, the decay of Hb concentration parallels the reduction of the mean number of hemosomes per reticulocyte, in comparison with normal reticulocytes. 5. In HeLa cells and epithelial cultured cells induced to synthesize Hb, it was shown that this biosynthesis is ever concomitant with the formation of hemosomes and depends on the presence of erythropoietin, as occurs in erythroid cells. 6. Studies on hemosomegenesis and Hb biosynthesis experimentally effected in epithelial cultured cells, allowed the interpretation of the sequence of events leading to hemosome formation in maturing erythroid cells. Simultaneously with iron uptake, mitochondria differentiate to lamellated bodies and, successively, expansions rise for ferruginous compounds and G polypeptides gathering, followed by prehemosome vesicles formation, which condense and change to prohemosomes that afterwards evolve to hemosomes. 7. These dynamics, and organellar Hb have been detected in immature erythrocytes of mammalians, including humans, avians, reptilians, amphibians and representative fish specimens. It appears that these events occur in the erythrocytary maturation of all vertebrate classes.

Diverse hematological phenotypes of β-thalassemia carriers.

PubMed

Luo, Hong-Yuan; Chui, David H K

2016-03-01

Most β-thalassemia carriers have mild anemia, low mean corpuscular volume and mean corpuscular hemoglobin, and elevated hemoglobin α2 (HbA2 ). However, there is considerable variability resulting from coinheritance with α- and/or δ-globin gene mutations, dominant inheritance of β-thalassemia mutations, highly unstable variant globin chains, large deletions removing part or all of the β-globin gene cluster, loss of heterozygosity of the β-globin gene cluster during development, or concomitant erythroid enzyme or membrane protein abnormalities. Recognition of the specific abnormality and correct diagnosis can allay anxiety and unnecessary investigation, help formulate treatment programs, and deliver appropriate genetic and family counseling. © 2016 New York Academy of Sciences.

Disruption of the Gardos channel (KCa3.1) in mice causes subtle erythrocyte macrocytosis and progressive splenomegaly.

PubMed

Grgic, Ivica; Kaistha, Brajesh P; Paschen, Steffen; Kaistha, Anuradha; Busch, Christoph; Si, Han; Köhler, Kernt; Elsässer, Hans-Peter; Hoyer, Joachim; Köhler, Ralf

2009-06-01

Gardos channel, the erythrocyte Ca(2+)-activated K(+) channel (K(Ca)3.1), is considered a major regulator of red blood cell (RBC) volume by mediating efflux of potassium and thus cell dehydration and shrinkage. However, the functional importance of K(Ca)3.1 in RBC in vivo is incompletely understood. Here, we used K(Ca)3.1(-/-)-mice to investigate the consequences of K(Ca)3.1 deficiency for RBC indices, functions, and sequestration. RBCs of K(Ca)3.1(-/-)-mice of all ages were mildly macrocytic but their biconcave appearance being preserved. RBC number, total hemoglobin, and hematocrit were unchanged in the adult K(Ca)3.1(-/-)-mice and increased in the premature K(Ca)3.1(-/-)-mice. Filterability, Ca(2+)-dependent volume decrease and osmotic tolerance of RBCs lacking K(Ca)3.1 were noticeably reduced when compared to RBC of wild-type littermates. Deformability to increasing shear stress was unchanged. Strikingly, K(Ca)3.1(-/-)-mice developed progressive splenomegaly which was considerable ( approximately 200% of controls) in the >6-month-old mice and was paralleled by increased iron deposition in the aged mice presumably as a consequence of enhanced RBC sequestration. Daily injections of the K(Ca)3.1-blocker TRAM-34 (120 mg/kg) also produced mild splenomegaly in wild-type mice. We conclude that genetic deficit of erythroid K(Ca)3.1 causes mild RBC macrocytosis, presumably leading to reduced filterability, and impairs volume regulation. These RBC defects result in mild but progressive splenomegaly.

Subunit dissociation in fish hemoglobins.

PubMed

Edelstein, S J; McEwen, B; Gibson, Q H

1976-12-10

The tetramer-dimer dissociation equilibria (K 4,2) of several fish hemoglobins have been examined by sedimentation velocity measurements with a scanner-computer system for the ultracentrifuge and by flash photolysis measurements using rapid kinetic methods. Samples studied in detail included hemoglobins from a marine teleost, Brevoortia tyrannus (common name, menhaden); a fresh water teleost, Cyprinus carpio, (common name, carp); and an elasmobranch Prionace glauca (common name, blue shark). For all three species in the CO form at pH 7, in 0.1 M phosphate buffer, sedimentation coefficients of 4.3 S (typical of tetrameric hemoglobin) are observed in the micromolar concentration range. In contrast, mammalian hemoglobins dissociate appreciably to dimers under these conditions. The inability to detect dissociation in three fish hemoglobins at the lowest concentrations examined indicates that K 4,2 must have a value of 10(-8) M or less. In flash photolysis experiments on very dilute solutions in long path length cells, two kinetic components were detected with their proportions varying as expected for an equilibrium between tetramers (the slower component) and dimers (the faster component); values of K 4,2 for the three fish hemoglobins in the range 10(-9) to 10(-8) M were calculated from these data. Thus, the values of K 4,2 for liganded forms of the fish hemoglobins appear to be midway between the value for liganded human hemoglobin (K 4,2 approximately 10(-6) M) and unliganded human hemoglobin (K 4,2 approximately 10(-12) M). This conclusion is supported by measurements on solutions containing guanidine hydrochloride to enhance the degree of dissociation. All three fish hemoglobins are appreciably dissociated at guanidine concentrations of about 0.8 M, which is roughly midway between the guanidine concentrations needed to cause comparable dissociation of liganded human hemoglobin (about 0.4 M) and unliganded human hemoglobin (about 1.6 M). Kinetic measurements on solutions containing guanidine hydrochloride indicated that there are changes in both the absolute rates and the proportions of the fast and slow components, which along with other factors complicated the analysis of the data in terms of dissociation constants. Measurements were also made in solutions containing urea to promote dissociation, but with this agent very high concentrations (about 6 M) were required to give measureable dissociation and the fish hemoglobins were unstable under these conditions, with appreciable loss of absorbance spectra in both the sedimentation and kinetic experiments.

Gene Therapy in a Patient with Sickle Cell Disease.

PubMed

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

2017-03-02

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

A Functional Element Necessary for Fetal Hemoglobin Silencing

PubMed Central

Sankaran, Vijay G.; Xu, Jian; Byron, Rachel; Greisman, Harvey A.; Fisher, Chris; Weatherall, David J.; Sabath, Daniel E.; Groudine, Mark; Orkin, Stuart H.; Premawardhena, Anuja; Bender, M.A.

2011-01-01

BACKGROUND An improved understanding of the regulation of the fetal hemoglobin genes holds promise for the development of targeted therapeutic approaches for fetal hemoglobin induction in the β-hemoglobinopathies. Although recent studies have uncovered trans-acting factors necessary for this regulation, limited insight has been gained into the cis-regulatory elements involved. METHODS We identified three families with unusual patterns of hemoglobin expression, suggestive of deletions in the locus of the β-globin gene (β-globin locus). We performed array comparative genomic hybridization to map these deletions and confirmed breakpoints by means of polymerase-chain-reaction assays and DNA sequencing. We compared these deletions, along with previously mapped deletions, and studied the trans-acting factors binding to these sites in the β-globin locus by using chromatin immunoprecipitation. RESULTS We found a new (δβ)0-thalassemia deletion and a rare hereditary persistence of fetal hemoglobin deletion with identical downstream breakpoints. Comparison of the two deletions resulted in the identification of a small intergenic region required for γ-globin (fetal hemoglobin) gene silencing. We mapped a Kurdish β0-thalassemia deletion, which retains the required intergenic region, deletes other surrounding sequences, and maintains fetal hemoglobin silencing. By comparing these deletions and other previously mapped deletions, we elucidated a 3.5-kb intergenic region near the 5′ end of the δ-globin gene that is necessary for γ-globin silencing. We found that a critical fetal hemoglobin silencing factor, BCL11A, and its partners bind within this region in the chromatin of adult erythroid cells. CONCLUSIONS By studying three families with unusual deletions in the β-globin locus, we identified an intergenic region near the δ-globin gene that is necessary for fetal hemoglobin silencing. (Funded by the National Institutes of Health and others.) PMID:21879898

Human erythrocytes analyzed by generalized 2D Raman correlation spectroscopy

NASA Astrophysics Data System (ADS)

Wesełucha-Birczyńska, Aleksandra; Kozicki, Mateusz; Czepiel, Jacek; Łabanowska, Maria; Nowak, Piotr; Kowalczyk, Grzegorz; Kurdziel, Magdalena; Birczyńska, Malwina; Biesiada, Grażyna; Mach, Tomasz; Garlicki, Aleksander

2014-07-01

The most numerous elements of the blood cells, erythrocytes, consist mainly of two components: homogeneous interior filled with hemoglobin and closure which is the cell membrane. To gain insight into their specific properties we studied the process of disintegration, considering these two constituents, and comparing the natural aging process of human healthy blood cells. MicroRaman spectra of hemoglobin within the single RBC were recorded using 514.5, and 785 nm laser lines. The generalized 2D correlation method was applied to analyze the collected spectra. The time passed from blood donation was regarded as an external perturbation. The time was no more than 40 days according to the current storage limit of blood banks, although, the average RBC life span is 120 days. An analysis of the prominent synchronous and asynchronous cross peaks allow us to get insight into the mechanism of hemoglobin decomposition. Appearing asynchronous cross-peaks point towards globin and heme separation from each other, while synchronous shows already broken globin into individual amino acids. Raman scattering analysis of hemoglobin "wrapping", i.e. healthy erythrocyte ghosts, allows for the following peculiarity of their behavior. The increasing power of the excitation laser induced alterations in the assemblage of membrane lipids. 2D correlation maps, obtained with increasing laser power recognized as an external perturbation, allows for the consideration of alterations in the erythrocyte membrane structure and composition, which occurs first in the proteins. Cross-peaks were observed indicating an asynchronous correlation between the senescent-cell antigen (SCA) and heme or proteins vibrations. The EPR spectra of the whole blood was analyzed regarding time as an external stimulus. The 2D correlation spectra points towards participation of the selected metal ion centers in the disintegration process.

White Matter Damage Relates to Oxygen Saturation in Children With Sickle Cell Anemia Without Silent Cerebral Infarcts.

PubMed

Kawadler, Jamie M; Kirkham, Fenella J; Clayden, Jonathan D; Hollocks, Matthew J; Seymour, Emma L; Edey, Rosanna; Telfer, Paul; Robins, Andrew; Wilkey, Olu; Barker, Simon; Cox, Tim C S; Clark, Chris A

2015-07-01

Sickle cell anemia is associated with compromised oxygen-carrying capability of hemoglobin and a high incidence of overt and silent stroke. However, in children with no evidence of cerebral infarction, there are changes in brain morphometry relative to healthy controls, which may be related to chronic anemia and oxygen desaturation. A whole-brain tract-based spatial statistics analysis was carried out in 25 children with sickle cell anemia with no evidence of abnormality on T2-weighted magnetic resonance imaging (13 male, age range: 8-18 years) and 14 age- and race-matched controls (7 male, age range: 10-19 years) to determine the extent of white matter injury. The hypotheses that white matter damage is related to daytime peripheral oxygen saturation and steady-state hemoglobin were tested. Fractional anisotropy was found to be significantly lower in patients in the subcortical white matter (corticospinal tract and cerebellum), whereas mean diffusivity and radial diffusivity were higher in patients in widespread areas. There was a significant negative relationship between radial diffusivity and oxygen saturation (P<0.05) in the anterior corpus callosum and a trend-level negative relationship between radial diffusivity and hemoglobin (P<0.1) in the midbody of the corpus callosum. These data show widespread white matter abnormalities in a sample of asymptomatic children with sickle cell anemia, and provides for the first time direct evidence of a relationship between brain microstructure and markers of disease severity (eg, peripheral oxygen saturation and steady-state hemoglobin). This study suggests that diffusion tensor imaging metrics may serve as a biomarker for future trials of reducing hypoxic exposure. © 2015 American Heart Association, Inc.