Stimulation of K-C1 cotransport in rat red cells by a hemolytic anemia-producing metabolite of dapsone

1989 ◽  
Vol 256 (2) ◽  
pp. C265-C272 ◽  
Author(s):  
M. Haas ◽  
J. H. Harrison
Keyword(s):  
Red Blood Cells ◽  
Hemolytic Anemia ◽  
Blood Cells ◽  
Pneumocystis Carinii ◽  
Fold Increase ◽  
Sh Groups ◽  
Splenic Uptake ◽  
Stimulation Of ◽  
In Cells

Dapsone, a sulfone compound used in the treatment of leprosy and, more recently, Pneumocystis carinii pneumonia, produces as a major side effect a hemolytic anemia. This anemia is characterized by oxidation of hemoglobin to methemoglobin and increased splenic uptake of red blood cells. Using a rat model, Grossman and Jollow (J. Pharmacol. Exp. Ther. 244: 118-125, 1988) found that dapsone hydroxylamine (DDS-NOH), a dapsone metabolite, is responsible for its hemolytic effect in vivo. DDS-NOH also promotes hemoglobin binding to SH groups on rat red cell membrane proteins (Budinsky et al., FASEB J. 2: A801, 1988). Since the binding of hemoglobin and other reagents (e.g., N-ethylmaleimide) to membrane SH groups has been associated with increased K transport in red blood cells, we examined the effect of DDS-NOH on K efflux from rat red blood cells in vitro. Cells shrink when exposed to DDS-NOH (100 microM) in media with plasma-like ionic composition. This shrinkage is prevented if extracellular K is raised to 110 mM or if intra- and extracellular Cl are replaced by methylsulfate (MeSO4), suggesting involvement of a K-Cl cotransport pathway. Indeed, 100 microM DDS-NOH produces a 4- to 5-fold increase in K efflux in cells containing Cl but less than a 2-fold increase in cells containing MeSO4. This stimulatory effect is specific for K; Na efflux is slightly inhibited by 100 microM DDS-NOH. The concentrations of DDS-NOH required for half-maximal stimulation of Cl-dependent K efflux (53 microM) is similar to its half-maximal hemolytic concentration in rats (approximately 100 microM). Furthermore, the stimulation of Cl-dependent K efflux by DDS-NOH is greater than 80% reversed by subsequent treatment of the cells with dithiothreitol, suggesting involvement of SH groups. Our results indicate that DDS-NOH exposure stimulates an apparent K-Cl cotransport in rat red blood cells, resulting in cell shrinkage under physiological ionic conditions. Since shrinkage of red blood cells renders them less deformable (Mohandas et al., J. Clin. Invest. 66: 563-573, 1980), this suggests a pathophysiological mechanism whereby DDS-NOH exposure in vivo could promote increased splenic uptake of red blood cells and hemolytic anemia.

scholarly journals The Effects of Concentrated Eluted Anti-Red Blood Cell Antibodies on the in Vivo Survival of Normal Red Blood Cells

Blood ◽  
1960 ◽  
Vol 15 (4) ◽  
pp. 525-533 ◽  
Author(s):  
NEIL W. CULP ◽  
HUGH CHAPLIN
Keyword(s):  
Blood Cell ◽  
Red Blood Cells ◽  
Hemolytic Anemia ◽  
Normal Control ◽  
Red Blood Cell ◽  
Blood Cells ◽  
Red Cells ◽  
Significant Alteration ◽  
Red Cell

Abstract 1. A method has been described for the preparation and sterilization of a concentrated eluate from human red cell stroma. 2. Red cells sensitized by such an eluate prepared from normal control red cells showed entirely normal in vivo survival, as did cells sensitized by eluate from anti-H coated cells. 3. Sensitization of red cells by concentrated eluates from a patient with Coombs-negative acquired hemolytic anemia and from a patient with Coombs-positive acquired hemolytic anemia did not cause significant alteration in the in vivo survival of the red cells. 4. Red cells sensitized by the concentrated eluate from anti-D sensitized cells disappeared from the recipient’s circulation very rapidly and were sequestered in the spleen, indicating preservation of the physiologic properties of the antibody throughout the elution, concentration and sterilization procedures.

scholarly journals Efficacy of Butanolic Fraction of Cocos Nucifera's Root Aqueous Extract on Induced Anemia Treatment

2021 ◽  
Vol 13 (2) ◽  
pp. 49
Author(s):  
Tchogou AP ◽  
Sènou M ◽  
Agbogba F ◽  
Lokonon JE ◽  
Medoatinsa SE ◽  
...  
Keyword(s):  
Red Blood Cells ◽  
Aqueous Extract ◽  
Blood Cells ◽  
Complete Blood Count ◽  
Cocos Nucifera ◽  
Coastal Plant ◽  
Dose Dependent ◽  
Anemia Treatment ◽  
Stimulation Of

Cocos nucifera was a coastal plant whose roots were used in pharmacopoeia to treat anemia in Benin. The aqueous extract from its roots stimulated the synthesis of hemoglobin. The aim of this work was to test in vivo the efficacy of the butanolic fraction of the extract in the treatment of anemia. Methods: Wistar rats were anemic with phenylhydrazine for two days. From D2 to D15, some were treated by gavage with the butanolic fraction of the aqueous extract of Cocos nucifera roots at the dose of 40 mg or 60 mg / kg of body weight / day, others were treated with vitafer (an anti-anemic drug) or with distilled water. The rats blood were collected on days D0, D2, D7, D10 and D15 for the complete blood count and the osmotic resistance of the red blood cells. Results: On D2, phenylhydrazine significantly lowered the hemoglobin level and the number of red blood cells, which were respectively corrected on D10 and D15 by the fraction of extract with release of hypochromic macrocytes. However, the effect was slower than that of the crude extract, was not specific to erythropoiesis because it also stimulated thrombopoiesis and was not dose-dependent. Conclusion: The butanolic fraction of the aqueous extract of Cocos nucifera roots corrected anemia by stimulation of hematopoiesis. The observed biological activity would probably be linked to anthocyanins which are mainly isolated by butanol. These results contribute to a better knowledge of bioactive compounds of our antianemic plants.

ACE-536, a Novel, GDF-Trap, Promotes Rapid Increase of Red Blood Cells In Vivo in An EPO-Independent Manner.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2505-2505
Author(s):  
Dianne Mitchell ◽  
Samuel Cadena ◽  
Chris Rogers ◽  
June Liu ◽  
Kathleen Tomkinson ◽  
...  
Keyword(s):  
Red Blood Cells ◽  
Blood Cells ◽  
Gene Array ◽  
Subcutaneous Administration ◽  
Fold Increase ◽  
Recombinant Erythropoietin ◽  
Erythroid Progenitors ◽  
Independent Manner ◽  
Number Of Patients

Abstract Abstract 2505 Poster Board II-482 Anemia is a common and debilitating complication associated with cancer chemotherapy, which depletes and prevents formation of red blood cells, and leads to incapacitating fatigue. The most common treatment for anemia involves administering recombinant erythropoietin (EPO); however, there are limitations with this form of therapy. A significant number of patients exhibit resistance to EPO treatment and several studies suggest in some cases EPO treatment can worsen patients' outcomes. Consequently, novel, non-EPO based therapeutics for anemia are needed. Several members of the TGF-β superfamily have been described to play a role in erythropoiesis. We developed ACE-536, a novel, GDF trap derived from the Type II activin receptor fused to the Fc region of IgG1, which binds to and inhibits several ligands in the TGF-β superfamily, and studied its effect on erythrocyte development. In vivo subcutaneous administration of ACE-536 (10mg/kg, or an equal volume of TBS vehicle control) in mice twice weekly resulted in significant increases of 6–9% in hematocrit, hemoglobin content, and red blood cell (RBC) count (P < 0.01) over the vehicle-only group after 4 days, although these blood parameters were already significantly increased 24 hours post-treatment. These observations were seen even in the presence of an EPO neutralizing antibody suggesting that EPO is not directing the initial RBC response. Moreover, it was shown that in this same 4 day period, treatment with ACE-536 did not result in altered EPO mRNA or protein expression, suggesting this drug acts independently of EPO. Furthermore, ACE-536 treatment resulted in a two-fold increase in CFU-E erythrocyte precursor populations in the spleen compared to the vehicle-only group, with no significant alterations in the levels of BFU-E precursor numbers. Gene array studies were used to characterize the mechanism by which ACE-536 alters erythropoiesis, and demonstrated that ACE-536 reduced the expression of numerous genes involved in erythroid differentiation. Thus, by delaying terminal differentiation, ACE-536 enables late-stage, erythroid progenitors to undergo addition cycles of proliferation, ultimately leading to the rapid increase in mature red blood cells. In conclusion, this study provides evidence that ACE-536 promotes development of red blood cells via an EPO-independent mechanism, and may prove to be an effective alternative to EPO therapy for patients suffering from anemia. Disclosures: Mitchell: Acceleron Pharma: Employment. Cadena:Acceleron Pharma: Employment. Rogers:Acceleron Pharma: Employment. Liu:Acceleron Pharma: Employment. Tomkinson:Acceleron Pharma: Employment. Barberio:Acceleron Pharma: Employment. Grinberg:Acceleron Pharma: Employment. Underwood:Acceleron Pharma: Employment. Pearsall:Acceleron Pharma: Employment. Kumar:Acceleron Pharma: Employment.

scholarly journals Efficacy of Butanolic Fraction of Cocos Nucifera's Root Aqueous Extract on Induced Anemia Treatment

2021 ◽  
Vol 13 (1) ◽  
pp. 8
Author(s):  
A. P. Tchogou ◽  
M. Sènou ◽  
F. Agbogba ◽  
J. E. Lokonon ◽  
S. E. Medoatinsa ◽  
...  
Keyword(s):  
Red Blood Cells ◽  
Aqueous Extract ◽  
Blood Cells ◽  
Complete Blood Count ◽  
Cocos Nucifera ◽  
Coastal Plant ◽  
Dose Dependent ◽  
Anemia Treatment ◽  
Stimulation Of

Cocos nucifera was a coastal plant whose roots were used in pharmacopoeia to treat anemia in Benin. The aqueous extract from its roots stimulated the synthesis of hemoglobin. The aim of this work was to test in vivo the efficacy of the butanolic fraction of the extract in the treatment of anemia. Methods: Wistar rats were anemic with phenylhydrazine for two days. From D2 to D15, some were treated by gavage with the butanolic fraction of the aqueous extract of Cocos nucifera roots at the dose of 40 mg or 60 mg/kg of body weight/day, others were treated with vitafer (an anti-anemic drug) or with distilled water. The rats blood were collected on days D0, D2, D7, D10 and D15 for the complete blood count and the osmotic resistance of the red blood cells. Results: On D2, phenylhydrazine significantly lowered the hemoglobin level and the number of red blood cells, which were respectively corrected on D10 and D15 by the fraction of extract with release of hypochromic macrocytes. However, the effect was slower than that of the crude extract, was not specific to erythropoiesis because it also stimulated thrombopoiesis and was not dose-dependent. Conclusion: The butanolic fraction of the aqueous extract of Cocos nucifera roots corrected anemia by stimulation of hematopoiesis. The observed biological activity would probably be linked to anthocyanins which are mainly isolated by butanol. These results contribute to a better knowledge of bioactive compounds of our antianemic plants.

Ultrastructural observations on the in vitro cytoadherence of Plasmodium falciparum infected red blood cells

1990 ◽  
Vol 48 (3) ◽  
pp. 914-915
Author(s):  
D.J.P. Ferguson ◽  
A.R. Berendt ◽  
J. Tansey ◽  
K. Marsh ◽  
C.I. Newbold
Keyword(s):  
Plasmodium Falciparum ◽  
Red Blood Cells ◽  
Blood Cells ◽  
Umbilical Vein ◽  
Cell Types ◽  
Amelanotic Melanoma ◽  
Cytoplasmic Process ◽  
Umbilical Vein Endothelial Cells

In human malaria, the most serious clinical manifestation is cerebral malaria (CM) due to infection with Plasmodium falciparum. The pathology of CM is thought to relate to the fact that red blood cells containing mature forms of the parasite (PRBC) cytoadhere or sequester to post capillary venules of various tissues including the brain. This in vivo phenomenon has been studied in vitro by examining the cytoadherence of PRBCs to various cell types and purified proteins. To date, three Ijiost receptor molecules have been identified; CD36, ICAM-1 and thrombospondin. The specific changes in the PRBC membrane which mediate cytoadherence are less well understood, but they include the sub-membranous deposition of electron-dense material resulting in surface deformations called knobs. Knobs were thought to be essential for cytoadherence, lput recent work has shown that certain knob-negative (K-) lines can cytoadhere. In the present study, we have used electron microscopy to re-examine the interactions between K+ PRBCs and both C32 amelanotic melanoma cells and human umbilical vein endothelial cells (HUVEC).We confirm previous data demonstrating that C32 cells possess numerous microvilli which adhere to the PRBC, mainly via the knobs (Fig. 1). In contrast, the HUVEC were relatively smooth and the PRBCs appeared partially flattened onto the cell surface (Fig. 2). Furthermore, many of the PRBCs exhibited an invagination of the limiting membrane in the attachment zone, often containing a cytoplasmic process from the endothelial cell (Fig. 2).

The Ullrastructure of Platelet Participation in Hemostasis

1965 ◽  
Vol 13 (01) ◽  
pp. 065-083 ◽  
Author(s):  
Shirley A. Johnson ◽  
Ronaldo S. Balboa ◽  
Harlan J. Pederson ◽  
Monica Buckley
Keyword(s):  
Platelet Aggregation ◽  
Red Blood Cells ◽  
Blood Cells ◽  
Guinea Pigs ◽  
Platelet Factor ◽  
Mesenteric Vessels ◽  
Platelet Aggregates ◽  
Electron Lucent

SummaryThe ultrastructure of platelet aggregation in vivo in response to bleeding brought about by transection of small mesenteric vessels in rats and guinea pigs has been studied. Platelets aggregate, degranulate and separating membranes disappear in parallel with fibrin appearance which is first seen at several loci after 30 seconds of bleeding. About 40 per cent of the electron opaque granules, some of which contain platelet factor 3 have disappeared after one minute of bleeding while the electron lucent granules increase by 70 per cent suggesting that some of them may be empty vesicles. Most of the platelet aggregates of the random type disappear leaving clumped red blood cells entrapped by a network of fibrin fibers which emanate from the remains of platelet aggregates of the rosette type to maintain hemostasis.

Cytotoxicity of chitosan ultrafine nanoshuttles on MCF-7 cell line as surrogate model for breast cancer

2020 ◽  
Vol 17 ◽  
Author(s):  
Tarek Faris ◽  
Gamaleldin I. Harisa ◽  
Fars K. Alanazi ◽  
Mohamed M. Badran ◽  
Afraa Mohammad Alotaibi ◽  
...  
Keyword(s):  
Red Blood Cells ◽  
Factorial Design ◽  
Cell Line ◽  
Cell Lines ◽  
Blood Cells ◽  
Sodium Tripolyphosphate ◽  
Physicochemical Characterization ◽  
Spherical Shape ◽  
Mcf 7

Aim: This study aimed to explore an affordable technique for the fabrication of Chitosan Nanoshuttles (CSNS) at the ultrafine nanoscale less than 100 nm with improved physicochemical properties, and cytotoxicity on the MCF-7 cell line. Background: Despite several studies reported that the antitumor effect of CS and CSNS could achieve intracellular compartment target ability, no enough available about this issue and further studies are required to address this assumption. Objectives: The objective of the current study was to investigate the potential processing variables for the production of ultrafine CSNS (> 100 nm) using Box-Benhken Design factorial design (BBD). This was achieved through a study of the effects of processing factors, such as CS concentration, CS/TPP ratio, and pH of the CS solution, on PS, PDI, and ZP. Moreover, the obtained CSNS was evaluated for physicochemical characteristics, morphology Also, hemocompatibility, and cytotoxicity using Red Blood Cells (RBCs) and MCF-7 cell lines were investigated. Methods: Box-Benhken Design factorial design (BBD) was used in the analysis of different selected variables. The effects of CS concentration, sodium tripolyphosphate (TPP) ratio, and pH on particle size, Polydispersity Index (PDI), and Zeta Potential (ZP) were measured. Subsequently, the prepared CS nanoshuttles were exposed to stability studies, physicochemical characterization, hemocompatibility, and cytotoxicity using red blood cells and MCF-7 cell lines as surrogate models for in vivo study. Result: The present results revealed that the optimized CSNS have ultrafine nanosize, (78.3±0.22 nm), homogenous with PDI (0.131±0.11), and ZP (31.9±0.25 mV). Moreover, CSNS have a spherical shape, amorphous in structure, and physically stable. Also, CSNS has biological safety as indicated by a gentle effect on red blood cell hemolysis, besides, the obtained nanoshuttles decrease MCF-7 viability. Conclusion: The present findings concluded that the developed ultrafine CSNS has unique properties with enhanced cytotoxicity. thus promising for use in intracellular organelles drug delivery.

scholarly journals Multimodal Diagnostics of Microrheologic Alterations in Blood of Coronary Heart Disease and Diabetic Patients

Diagnostics ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 76
Author(s):  
Anastasia Maslianitsyna ◽  
Petr Ermolinskiy ◽  
Andrei Lugovtsov ◽  
Alexandra Pigurenko ◽  
Maria Sasonko ◽  
...  
Keyword(s):  
Coronary Heart Disease ◽  
Heart Disease ◽  
Red Blood Cells ◽  
Blood Cells ◽  
Optical Methods ◽  
Diabetic Patients ◽  
Aggregation Index ◽  
Significant Difference

Coronary heart disease (CHD) has serious implications for human health and needs to be diagnosed as early as possible. In this article in vivo and in vitro optical methods are used to study blood properties related to the aggregation of red blood cells in patients with CHD and comorbidities such as type 2 diabetes mellitus (T2DM). The results show not only a significant difference of the aggregation in patients compared to healthy people, but also a correspondence between in vivo and in vitro parameters. Red blood cells aggregate in CHD patients faster and more numerously; in particular the aggregation index increases by 20 ± 7%. The presence of T2DM also significantly elevates aggregation in CHD patients. This work demonstrates multimodal diagnostics and monitoring of patients with socially significant pathologies.

scholarly journals Role of Calcium in Phosphatidylserine Externalisation in Red Blood Cells from Sickle Cell Patients

Anemia ◽  
2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Erwin Weiss ◽  
David Charles Rees ◽  
John Stanley Gibson
Keyword(s):  
Red Blood Cells ◽  
Sickle Cell ◽  
Blood Cells ◽  
Phosphatidylserine Exposure ◽  
Channel Inhibition ◽  
Cation Conductance ◽  
Gardos Channel ◽  
Cation Permeability

Phosphatidylserine exposure occurs in red blood cells (RBCs) from sickle cell disease (SCD) patients and is increased by deoxygenation. The mechanisms responsible remain unclear. RBCs from SCD patients also have elevated cation permeability, and, in particular, a deoxygenation-induced cation conductance which mediates entry, providing an obvious link with phosphatidylserine exposure. The role of was investigated using FITC-labelled annexin. Results confirmed high phosphatidylserine exposure in RBCs from SCD patients increasing upon deoxygenation. When deoxygenated, phosphatidylserine exposure was further elevated as extracellular [] was increased. This effect was inhibited by dipyridamole, intracellular chelation, and Gardos channel inhibition. Phosphatidylserine exposure was reduced in high saline. levels required to elicit phosphatidylserine exposure were in the low micromolar range. Findings are consistent with entry through the deoxygenation-induced pathway (), activating the Gardos channel. [] required for phosphatidylserine scrambling are in the range achievablein vivo.

Clock gene-independent daily regulation of haemoglobin oxidation in red blood cells

2021 ◽  
Author(s):  
Andrew D. Beale ◽  
Priya Crosby ◽  
Utham K. Valekunja ◽  
Rachel S. Edgar ◽  
Johanna E. Chesham ◽  
...  
Keyword(s):  
Circadian Rhythms ◽  
Red Blood Cells ◽  
Blood Cells ◽  
Human Subjects ◽  
Developmental Regulation ◽  
Physiological Role ◽  
Cell Types ◽  
The Body

AbstractCellular circadian rhythms confer daily temporal organisation upon behaviour and physiology that is fundamental to human health and disease. Rhythms are present in red blood cells (RBCs), the most abundant cell type in the body. Being naturally anucleate, RBC circadian rhythms share key elements of post-translational, but not transcriptional, regulation with other cell types. The physiological function and developmental regulation of RBC circadian rhythms is poorly understood, however, partly due to the small number of appropriate techniques available. Here, we extend the RBC circadian toolkit with a novel biochemical assay for haemoglobin oxidation status, termed “Bloody Blotting”. Our approach relies on a redox-sensitive covalent haem-haemoglobin linkage that forms during cell lysis. Formation of this linkage exhibits daily rhythms in vitro, which are unaffected by mutations that affect the timing of circadian rhythms in nucleated cells. In vivo, haemoglobin oxidation rhythms demonstrate daily variation in the oxygen-carrying and nitrite reductase capacity of the blood, and are seen in human subjects under controlled laboratory conditions as well as in freely-behaving humans. These results extend our molecular understanding of RBC circadian rhythms and suggest they serve an important physiological role in gas transport.

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