Blood filterability and hemoglobin-oxygen affinity in diabetic patients with and without retinopathy

Patients with idiopathic erythrocytosis are directed to targeted genetic testing including nine genes involved in oxygen sensing pathway in kidneys, erythropoietin signal transduction in pre-erythrocytes and hemoglobin-oxygen affinity regulation in mature erythrocytes. However, in more than 60% of cases the genetic cause remains undiagnosed, suggesting that other genes and mechanisms must be involved in the disease development. This review aims to explore additional molecular mechanisms in recognized erythrocytosis pathways and propose new pathways associated with this rare hematological disorder. For this purpose, a comprehensive review of the literature was performed and different in silico tools were used. We identified genes involved in several mechanisms and molecular pathways, including mRNA transcriptional regulation, post-translational modifications, membrane transport, regulation of signal transduction, glucose metabolism and iron homeostasis, which have the potential to influence the main erythrocytosis-associated pathways. We provide valuable theoretical information for deeper insight into possible mechanisms of disease development. This information can be also helpful to improve the current diagnostic solutions for patients with idiopathic erythrocytosis.

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

Scientific Reports ◽

10.1038/srep13147 ◽

2015 ◽

Vol 5 (1) ◽

Cited By ~ 3

Author(s):

William G. O’Brien III ◽

Vladimir Berka ◽

Ah-Lim Tsai ◽

Zhaoyang Zhao ◽

Cheng Chi Lee

Keyword(s):

Oxygen Affinity ◽

Hemoglobin Oxygen Affinity ◽

Metabolic Performance

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Features of ozone effect on oxygen-dependent processes in the blood under hypoxic conditions

Regional blood circulation and microcirculation ◽

10.24884/1682-6655-2021-20-3-70-76 ◽

2021 ◽

Vol 20 (3) ◽

pp. 70-76

Author(s):

V. V. Zinchuk ◽

E. S. Biletskaya

Keyword(s):

Malonic Dialdehyde ◽

Oxygen Affinity ◽

Diene Conjugates ◽

Physiological Factor ◽

Sodium Hydrosulfide ◽

Hypoxic Conditions ◽

Hemoglobin Oxygen Affinity ◽

Gaseous Transmitters ◽

Dependent Processes

Introduction. Ozone is a physiological factor that can change hemoglobin oxygen affinity and the formation of gaseous transmitters (NO, H2S). The aim is to study the effect of ozone with gaseous transmitters donors on oxygen-dependent processes in the blood under hypoxic conditions in vitro. Materials and methods. Blood samples were divided into 6 groups of 3 ml each. Groups 2, 4, 5, 6 were pretreated with a deoxygenating gas mixture (5.5 % CO2; 94.5 % N2). In groups 3, 4, 5, 6, ozonized isotonic sodium chloride solution (with an ozone concentration of 6 mg/l) was added, and in groups 5 and 6, the donors of gas transmitters nitroglycerin and sodium hydrosulfide, respectively, were additionally introduced. Results. Pre-deoxygenation reduces the effect of ozone on oxygen transport in the blood. Nitroglycerin prevents this effect. The action of ozone under hypoxic conditions leads to an increase of content of NO3-/NO2- and H2S, and combination with nitroglycerin and sodium hydrosulfide increase these parameters. Deoxygenation due to ozone reduces parameters of lipid peroxidation (malonic dialdehyde, diene conjugates), retinol and α-tocopherol, and the same result in the nitroglycerin group. Conclusion. Under hypoxic conditions, a decrease in the effect of ozone on oxygen-dependent processes is reported. Nitroglycerin reduces its manifestation, while sodium hydrosulfide does not have a similar effect.

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Impact of voxelotor (GBT440) on unconjugated bilirubin and jaundice in sickle cell disease

Hematology Reports ◽

10.4081/hr.2018.7643 ◽

2018 ◽

Vol 10 (2) ◽

Cited By ~ 5

Author(s):

Paul Telfer ◽

Irene Agodoa ◽

Kathleen M. Fox ◽

Laurie Burke ◽

Timothy Mant ◽

...

Keyword(s):

Sickle Cell Disease ◽

Sickle Cell ◽

Oxygen Affinity ◽

Well Being ◽

Unconjugated Bilirubin ◽

Cell Disease ◽

Case Patient ◽

Disease Manifestation ◽

Patient Reported ◽

Hemoglobin Oxygen Affinity

For many patients with sickle cell disease (SCD), jaundice is a significant clinical disease manifestation that impacts on patient well-being. We report a case of a patient with SCD and chronic jaundice treated with voxelotor (GBT440), a novel small molecule hemoglobin oxygen affinity modulator and potential disease-modifying therapy for SCD. The case patient is a 27- year-old Black male with a long history of SCD with clinical jaundice and scleral icterus. After starting voxelotor, the patient reported that his jaundice cleared within one week, and that he felt much better with more energy, and was relieved after his eyes cleared. Voxelotor reduced bilirubin and unconjugated bilirubin (by up to 76%), and hemoglobin improved from 9.9 g/dL at baseline to 11.1 g/dL at 90 days. Jaundice impacts many adults with SCD, significantly impacting self-image. Voxelotor treatment reduced bilirubin levels and improved jaundice, resulting in an improved sense of well-being in our case patient.

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Effect of the Diphosphonate EHDP on Plasma Inorganic Phosphate and Hemoglobin Oxygen Affinity of Diabetic and Healthy Subjects

Advances in Experimental Medicine and Biology - Phosphate Metabolism ◽

10.1007/978-1-4613-4217-5_43 ◽

1977 ◽

pp. 423-430 ◽

Cited By ~ 4

Author(s):

Jørn Ditzel ◽

Chr. Hau ◽

Niels Daugaard

Keyword(s):

Healthy Subjects ◽

Inorganic Phosphate ◽

Oxygen Affinity ◽

Hemoglobin Oxygen Affinity

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Analysis of the relationship between hemoglobin-oxygen affinity and lipid peroxidation during fever.

Acta Biochimica Polonica ◽

10.18388/abp.1995_4670 ◽

1995 ◽

Vol 42 (1) ◽

pp. 69-74 ◽

Cited By ~ 6

Author(s):

M V Borisiuk ◽

V V Zinchuk

Keyword(s):

Lipid Peroxidation ◽

Malonic Dialdehyde ◽

Oxygen Affinity ◽

Alpha Tocopherol ◽

Diene Conjugates ◽

Tocopherol Concentration ◽

Hemoglobin Oxygen Affinity ◽

The Relationship ◽

Free Radical Lipid Oxidation ◽

Oxyhemoglobin Dissociation

Endogenous hyperthermia was induced in rabbits by i.v. pyrogenal administration. Hemoglobin-oxygen affinity and parameters of free radical lipid oxidation in plasma and red blood cells were measured. The content of diene conjugates, malonic dialdehyde and Schiff bases were determined at a pyrogenal dose of 4 minimal pyrogenic doses/kg, and iron-initiated chemiluminescence, catalase activity and alpha-tocopherol concentration were determined at 6 minimal pyrogenic doses/kg. A rightward shift of the real oxyhemoglobin dissociation curve and activation of lipid peroxidation were observed. Relationships between the parameters measured were analyzed. Decreased hemoglobin-oxygen affinity is considered to be a possible mechanism of activation of free radicals during fever.

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Hemoglobin-Oxygen Equilibrium in Cystic Fibrosis

PEDIATRICS ◽

10.1542/peds.59.6.919 ◽

1977 ◽

Vol 59 (6) ◽

pp. 919-926

Author(s):

Amnon Rosenthal ◽

Kon Taik Khaw ◽

Harry Shwachman

Keyword(s):

Cystic Fibrosis ◽

Tissue Oxygenation ◽

Oxygen Affinity ◽

Arterial Oxygen Tension ◽

Pulmonary Involvement ◽

Arterial Oxygen ◽

Blood Ph ◽

Hemoglobin Oxygen Affinity ◽

Systemic Oxygen ◽

2,3 Dpg

A study of 35 patients with cystic fibrosis demonstrated that increasing severity of pulmonary involvement was associated with a mild but definite increase in erythrocyte 2,3-diphosphoglycerate (2,3-DPG) and a decrease in hemoglobin affinity for oxygen. The predominant regulators of 2,3-DPG were blood pH, cardiac output, and systemic oxygen transport. No significant relationship was observed between erythrocyte 2,3-DPG content and arterial oxygen tension. Hypophosphatemia may have prevented a greater increase in erythrocyte 2,3-DPG content. The inadequate increase in 2,3-DPG and consequent insufficient change in hemoglobin-oxygen affinity, coupled with an insufficient compensatory erythrocytic response, may adversely affect tissue oxygenation in patients with severe cystic fibrosis.

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NTP pattern of avian embryonic red cells: role of RNA degradation and AMP deaminase/5′-nucleotidase activity

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00461.2002 ◽

2003 ◽

Vol 284 (3) ◽

pp. R771-R779 ◽

Cited By ~ 5

Author(s):

Rosemarie Baumann ◽

Robert Götz ◽

Stefanie Dragon

Keyword(s):

Hormonal Regulation ◽

Oxygen Affinity ◽

Erythroid Differentiation ◽

Rna Degradation ◽

Amp Deaminase ◽

Key Enzymes ◽

Allosteric Effectors ◽

Hemoglobin Oxygen Affinity ◽

Adult Hemoglobin

During terminal erythroid differentiation, degradation of RNA is a potential source for nucleotide triphosphates (NTPs) that act as allosteric effectors of hemoglobin. In this investigation, we assessed the developmental profile of RNA and purine/pyrimidine trinucleotides in circulating embryonic chick red blood cells (RBC). Extensive changes of the NTP pattern are observed which differ significantly from what is observed for adult RBC. The biochemical mechanisms have not been identified yet. Therefore, we studied the role of AMP deaminase and IMP/GMP 5′-nucleotidase, which are key enzymes for the regulation of the purine nucleotide pool. Finally, we tested the effect of major NTPs on the oxygen affinity of embryonic/adult hemoglobin. The results are as follows. 1) Together with ATP, UTP and CTP serve as allosteric effectors of hemoglobin. 2) Degradation of erythroid RNA is apparently a major source for NTPs. 3) Developmental changes of nucleotide content depend on the activities of key enzymes (AMP deaminase, IMP/GMP 5′-nucleotidase, and pyrimidine 5′-nucleotidase). 4) Oxygen-dependent hormonal regulation of AMP deaminase adjusts the red cell ATP concentration and therefore the hemoglobin oxygen affinity.

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Mechanism of red cell 2,3-diphosphoglycerate increase in neonatal lambs

Blood ◽

10.1182/blood.v61.5.920.920 ◽

1983 ◽

Vol 61 (5) ◽

pp. 920-924 ◽

Cited By ~ 4

Author(s):

NA Noble ◽

CA Jansen ◽

PW Nathanielsz ◽

KR Tanaka

Keyword(s):

Oxygen Affinity ◽

Glucose Consumption ◽

Red Cell ◽

Sequential Effects ◽

Blood Ph ◽

Tenfold Increase ◽

Hemoglobin Oxygen Affinity ◽

Ph Increase ◽

Neonatal Lambs

Abstract The tenfold increase in red cell 2,3-diphosphoglycerate (DPG) concentration that occurs during the first 5 days of life in lambs is an important adaptation to extrauterine life. In lambs, DPG reduces hemoglobin oxygen affinity by the Bohr effect. Our data on 10 neonatal lambs suggest that the biochemical mechanism underlying this DPG increase involves the following: (1) a rise in plasma glucose from 40 to 100 mg/dl in the first 48 hr of life, which allows for increased glucose consumption in the highly glucose-permeable neonatal RBC; (2) a transitory rise in blood pH begins at birth, peaks at about 20 hr, and falls slightly; (3) the pH increase coincides with a threefold increase in RBC fructose-1,6-diphosphate (FDP) concentration due, we believe, to pH activation of phosphofructokinase; (4) glycolytic intermediates after the glyceraldehyde-3-phosphate dehydrogenase (GAPD) step do not rise in the first 24 hr of life, possibly due to insufficient inorganic phosphate (Pi), a substrate of GAPD; (5) plasma Pi increases from about 7 mg/dl at birth to 11 mg/dl at 72 hr, activates the GAPD, and FDP levels decline; and (6) the in vitro activity of the DPG synthetic enzyme, DPG mutase, is increased 12-fold in neonatal compared to adult RBC. We conclude that the postnatal rise in DPG is explained at least in part by the sequential effects of these metabolic changes.

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