Shortened Lifespan of Red Blood Cells and the Effects of Erythropoietin in Rats with Nephrogenic Anemia.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1977-1977
Author(s):  
Yoshiyuki Iwatsuki ◽  
Koki Kitamura ◽  
Ken-ichi Suzuki
Keyword(s):  
Red Blood Cells ◽  
Peripheral Blood ◽  
Blood Cells ◽  
Time Course ◽  
Annexin V ◽  
Renal Anemia ◽  
Normal Donor ◽  
Human Erythropoietin ◽  
Male Wistar Rats ◽  
Rbc Count

Abstract Abstract 1977 Poster Board I-1000 Anemia is a common complication of chronic kidney disease (CKD), mainly due to the inability of the kidneys to secrete enough erythropoietin to adequately stimulate hematopoiesis. Further, given that the lifespan of red blood cells (RBCs) has been reported to be reduced in CKD patients, this reduction in RBC lifespan is believed to be a part of the etiology of renal anemia. In the present study, we focused on RBC survival and measured the lifespan of RBCs in rats with nephrogenic anemia. We also examined the effects of erythropoietin on RBC lifespan in this anemia model. Nephrogenic anemia was induced by oral administration of adenine (600 mg/kg/day for 10 days) to male Wistar rats. Progressive, serious anemia associated with increased levels of plasma creatinine was observed in the rats. On Day 40, the number of RBCs and hemoglobin (HGB) levels were lower in the adenine-treated rats than in normal, control rats (normal: 930×104/μL, anemic: 677×104/μL for RBC and normal: 17.2 g/dL, anemic: 13.4 g/dL for HGB). However, the number of reticulocytes did not change in the anemic rats (normal: 299×103/μL, anemic: 329×103/μL, P = 0.102). The percentage of annexin V-binding erythrocytes was increased in anemic rats (normal: 0.77%, anemic 1.76%) and inversely correlated with RBC count and HGB levels, suggesting that apoptosis of RBCs increased as anemia progressed. Taking these findings into account, we measured the lifespan of RBCs in rats with nephrogenic anemia. We transfused 5-chloromethylfluorescein diacetate (CMFDA)-labeled RBCs from normal donor rats into either normal or anemic recipients and determined the number of labeled RBCs present in the peripheral blood at various time points thereafter. The time course of the reduction in the percentage of labeled RBCs in peripheral blood revealed that the half-life (t1/2) of RBCs in anemic rats was shorter than in normal rats (normal: 22.5 d, anemic: 13.3 d). This reduction in RBC lifespan was also observed in a rat model of cisplatin-induced renal anemia. Injection of anemic rats with recombinant human erythropoietin (rhEPO) restored the number of RBCs and HGB concentration to normal levels. However, the t1/2of RBCs in these rats was not changed. The clearance of RBCs in anemic rats does not appear to be influenced by rhEPO injection. In conclusion, the survival of RBCs was reduced in rats with nephrogenic anemia, an observation consistent with the shortened survival time of RBCs in renal failure patients. This finding suggests that this model is suitable for investigating drugs which may be used in the treatment of renal anemia. Further, because EPO therapy did not affect the lifespan of RBCs, agents which improve the shortened RBC survival inherent in CKD patients may be useful in treating renal anemia. Disclosures: Iwatsuki: Astellas Pharma Inc.: Employment. Kitamura:Astellas Research Institute of America LLC: Employment. Suzuki:Astellas Pharma Inc.: Employment.

Increased Procoagulant Activity of Red Blood Cells from Patients with Homozygous Sickle Cell Disease and β-Thalassemia

1996 ◽  
Vol 76 (03) ◽  
pp. 322-327 ◽  
Author(s):  
Dominique Helley ◽  
Amiram Eldor ◽  
Robert Girot ◽  
Rolande Ducrocq ◽  
Marie-Claude Guillin ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Red Blood Cells ◽  
Sickle Cell ◽  
Blood Cells ◽  
Annexin V ◽  
Mean Value ◽  
Procoagulant Activity ◽  
Dependent Manner ◽  
Cell Disease ◽  
Homozygous Sickle Cell Disease

SummaryIt has recently been proved that, in vitro, red blood cells (RBCs) from patients with homozygous β-thalassemia behave as procoagulant cells. The procoagulant activity of β-thalassemia RBCs might be the result of an increased exposure of procoagulant phospholipids (i. e. phosphatidylserine) in the outer leaflet of the membrane. In order to test this hypothesis, we compared the catalytic properties of RBCs of patients with β-thalassemia and homozygous sickle cell disease (SS-RBCs) with that of controls. The catalytic parameters (Km, kcat) of prothrombin activation by factor Xa were determined both in the absence and in the presence of RBCs. The turn-over number (kcat) of the reaction was not modified by normal, SS- or (3-thalassemia RBCs. The Km was lower in the presence of normal RBCs (mean value: 9.1 µM) than in the absence of cells (26 µM). The Km measured in the presence of either SS-RBCs (mean value: 1.6 µM) or β-thalassemia RBCs (mean value: 1.5 pM) was significantly lower compared to normal RBCs (p <0.001). No significant difference was observed between SS-RBCs and p-thalassemia RBCs. Annexin V, a protein with high affinity and specificity for anionic phospholipids, inhibited the procoagulant activity of both SS-RBCs and (3-thalassemia RBCs, in a dose-dependent manner. More than 95% inhibition was achieved at nanomolar concentrations of annexin V. These results indicate that the procoagulant activity of both β-thalassemia RBCs and SS-RBCs may be fully ascribed to an abnormal exposure of phosphatidylserine at the outer surface of the red cells.

scholarly journals Dielectric characterization of Plasmodium falciparum -infected red blood cells using microfluidic impedance cytometry

2018 ◽  
Vol 15 (147) ◽  
pp. 20180416 ◽  
Author(s):  
C. Honrado ◽  
L. Ciuffreda ◽  
D. Spencer ◽  
L. Ranford-Cartwright ◽  
H. Morgan
Keyword(s):  
Plasmodium Falciparum ◽  
Dielectric Properties ◽  
Red Blood Cells ◽  
Blood Cells ◽  
Time Course ◽  
Fluorescent Protein ◽  
Clear Understanding ◽  
Infection Cycle ◽  
Dielectric Characterization ◽  
Impedance Cytometry

Although malaria is the world's most life-threatening parasitic disease, there is no clear understanding of how certain biophysical properties of infected cells change during the malaria infection cycle. In this article, we use microfluidic impedance cytometry to measure the dielectric properties of Plasmodium falciparum -infected red blood cells ( i- RBCs) at specific time points during the infection cycle. Individual parasites were identified within i- RBCs using green fluorescent protein (GFP) emission. The dielectric properties of cell sub-populations were determined using the multi-shell model. Analysis showed that the membrane capacitance and cytoplasmic conductivity of i- RBCs increased along the infection time course, due to membrane alterations caused by parasite infection. The volume ratio occupied by the parasite was estimated to vary from less than 10% at earlier stages, to approximately 90% at later stages. This knowledge could be used to develop new label-free cell sorting techniques for sample pre-enrichment, improving diagnosis.

scholarly journals The mechanism of adaptation of the organism of patients with chronic heart failure combined with vitamin D deficiency and the morphofunctional state of peripheral blood erythrocytes

2019 ◽  
Vol 10 (3) ◽  
pp. 352-357
Author(s):  
N. I. Baryla ◽  
I. P. Vakaliuk ◽  
S. L. Pоpеl’
Keyword(s):  
Heart Failure ◽  
Vitamin D ◽  
Chronic Heart Failure ◽  
Red Blood Cells ◽  
Vitamin D Deficiency ◽  
Peripheral Blood ◽  
Blood Cells ◽  
Functional Class ◽  
Exercise Stress ◽  
Control Group

The problem of structural changes in peripheral blood erythrocytes in patients with chronic heart failure in combination with vitamin D deficiency during exercise stress remains insufficiently studied. Vitamin receptors are located on smooth myocytes, endothelial cells, cardiomyocytes and blood cells. It affects the state of the cell membrane, the contractile function of the myocardium, the regulation of blood pressure, cardiac remodeling and reduction of left ventricular hypertrophy. Therefore, it is important to assess the level of vitamin D in blood plasma in individuals with chronic heart failure and to identify the effect of its deficiency on the state of peripheral red blood cells when performing a 6-minute walk test. A total of 75 patients of the main group with chronic heart failure stage II A, I–II functional class with different levels of vitamin D deficiency were examined. The control group included 25 patients with chronic heart failure stage II A, functional class I–II without signs of vitamin D deficiency. The average age of patients was 57.5 ± 7.5 years. All patients were asked to undergo the 6 minutes walking test. The level of total vitamin D in plasma was determined by enzyme immunoassay. Morphological studies of erythrocytes were performed on the light-optical and electron-microscopic level. The obtained results showed that patients of the main group with chronic heart failure had a decrease in vitamin D by 2.2 times compared with the control group. Correlation analysis showed a directly proportional relationship between vitamin D deficiency and the number of red blood cells of a modified form and red blood cells with low osmotic resistance. Dosed exercise stress in patients with chronic heart failure against a background of vitamin D deficiency leads to an increase in the number of reversibly and irreversibly deformed erythrocytes and a decrease in their osmotic stability. This indicates a disorder in the structural integrity of their membrane and can have negative consequences for the somatic health of such patients.

scholarly journals OVERVIEW OF MALARIA PARASITE AND ITS PREVENTION IN INDIA

2019 ◽  
Vol 8 (1) ◽  
Author(s):  
Adil Raza ◽  
Megha Chaudhary ◽  
Sonika Devi
Keyword(s):  
Red Blood Cells ◽  
Peripheral Blood ◽  
Blood Cells ◽  
Malaria Parasite ◽  
Plasmodium Species ◽  
Peripheral Blood Smear ◽  
Infected Mosquito ◽  
Protozoan Parasites ◽  
Malaria Parasites ◽  
Genus Plasmodium

Background: Malaria is a systematic disease caused by a parasite called Plasmodium which is transmitted into the human blood via female Anopheles mosquito. Malaria in humans is caused by four species of protozoan parasites of the genus Plasmodium: P. falciparum, P. vivax, P. ovale, and P. malariae. The parasite enters the human body through a mosquito bite and travel to the very crucial organ, the liver, where they multiply and come back to the bloodstream and destroy red blood cells. Malaria causes symptoms that typically include fever, tiredness, vomiting, and headaches. In severe cases it can cause yellow skin, seizures, coma, or death. Symptoms usually begin ten to fifteen days after being bitten by an infected mosquito. In those who have recently survived an infection, reinfection usually causes milder symptoms. Objectives: Isolation of different species of malaria parasites. The prevalence of malaria parasite in India. Methods: The procedure follows these steps: collection of peripheral blood, staining of smear with Leishman’s stain and examination of red blood cells for malaria parasites under the microscope. Results: We observed the plasmodium species in peripheral blood smear. Conclusion: Worldwide, the number of cases of malaria caused by Plasmodium falciparum, the most dangerous species of the parasite, is on the rise.

scholarly journals PIEZO1 and the mechanism of the long circulatory longevity of human red blood cells

2021 ◽  
Vol 17 (3) ◽  
pp. e1008496
Author(s):  
Simon Rogers ◽  
Virgilio L. Lew
Keyword(s):  
Red Blood Cells ◽  
Blood Cells ◽  
Time Course ◽  
Clinical Manifestations ◽  
Cell Subpopulation ◽  
Unexpected Finding ◽  
Human Red Blood Cells ◽  
Acceptable Model ◽  
New Finding ◽  
Extended Longevity

Human red blood cells (RBCs) have a circulatory lifespan of about four months. Under constant oxidative and mechanical stress, but devoid of organelles and deprived of biosynthetic capacity for protein renewal, RBCs undergo substantial homeostatic changes, progressive densification followed by late density reversal among others, changes assumed to have been harnessed by evolution to sustain the rheological competence of the RBCs for as long as possible. The unknown mechanisms by which this is achieved are the subject of this investigation. Each RBC traverses capillaries between 1000 and 2000 times per day, roughly one transit per minute. A dedicated Lifespan model of RBC homeostasis was developed as an extension of the RCM introduced in the previous paper to explore the cumulative patterns predicted for repetitive capillary transits over a standardized lifespan period of 120 days, using experimental data to constrain the range of acceptable model outcomes. Capillary transits were simulated by periods of elevated cell/medium volume ratios and by transient deformation-induced permeability changes attributed to PIEZO1 channel mediation as outlined in the previous paper. The first unexpected finding was that quantal density changes generated during single capillary transits cease accumulating after a few days and cannot account for the observed progressive densification of RBCs on their own, thus ruling out the quantal hypothesis. The second unexpected finding was that the documented patterns of RBC densification and late reversal could only be emulated by the implementation of a strict time-course of decay in the activities of the calcium and Na/K pumps, suggestive of a selective mechanism enabling the extended longevity of RBCs. The densification pattern over most of the circulatory lifespan was determined by calcium pump decay whereas late density reversal was shaped by the pattern of Na/K pump decay. A third finding was that both quantal changes and pump-decay regimes were necessary to account for the documented lifespan pattern, neither sufficient on their own. A fourth new finding revealed that RBCs exposed to levels of PIEZO1-medited calcium permeation above certain thresholds in the circulation could develop a pattern of early or late hyperdense collapse followed by delayed density reversal. When tested over much reduced lifespan periods the results reproduced the known circulatory fate of irreversible sickle cells, the cell subpopulation responsible for vaso-occlusion and for most of the clinical manifestations of sickle cell disease. Analysis of the results provided an insightful new understanding of the mechanisms driving the changes in RBC homeostasis during circulatory aging in health and disease.

Cell volume and metabolic dependence of NEM-activated K+-Cl- flux in human red blood cells

1985 ◽  
Vol 249 (1) ◽  
pp. C124-C128 ◽  
Author(s):  
P. K. Lauf ◽  
C. M. Perkins ◽  
N. C. Adragna
Keyword(s):  
Red Blood Cells ◽  
Cell Volume ◽  
Blood Cells ◽  
Time Course ◽  
Transport Activity ◽  
Human Red Blood Cells ◽  
Atp Breakdown ◽  
The Difference ◽  
Metabolic Dependence ◽  
K Transport

The effects of incubation in anisosmotic media and of metabolic depletion on ouabain-resistant (OR) Cl--dependent K+ influxes stimulated by N-ethylmaleimide (NEM) were studied in human red blood cells using Rb+ as K+ analogue. The NEM-stimulated but not the basal Rb+-Cl- influx measured in phosphate-buffered anisosmotic media was found to be cell volume dependent. When cellular ATP, [ATP]c, was lowered to less than 0.10 of its initial level by exposure to nonmetabolizable 2-deoxy-D-glucose, the NEM-stimulated but not the basal Cl--dependent Rb+ influxes were abolished. Metabolically depleted red blood cells subsequently repleted by incubation in glucose plus inosine regained the NEM-inducible Rb+ (K+) transport activity. The difference in the time course of ATP breakdown and Rb+ influx inhibition suggests that energization of the NEM-stimulated Rb+ flux by metabolism may involve factors additional to ATP.

The development and pathogenesis of Leucocytozoon simondi in Canada and domestic geese in Algonquin Park, Ontario

1976 ◽  
Vol 54 (5) ◽  
pp. 634-643 ◽  
Author(s):  
Sherwin S. Desser ◽  
Andrée K. Ryckman
Keyword(s):  
Red Blood Cells ◽  
Peripheral Blood ◽  
Blood Cells ◽  
Primary Infection ◽  
Clinical Signs ◽  
Peripheral Circulation ◽  
Branta Canadensis ◽  
Canada Geese ◽  
Severe Anemia ◽  
Branta Canadensis Interior

The development of Leucocytozoon simondi was studied in naturally and experimentally infected Branta canadensis maxima, Branta canadensis interior, and Anser domesticus. The number of mature round gametocytes in the peripheral blood of the Canada geese increased between days 9 and 15 post exposure (PE) and decreased rapidly thereafter. Mean peak parasitemias recorded on day 13 PE were (per 1000 red blood cells (RBC)): 8 gametocytes in B.c. maxima, 16 gametocytes in B.c. interior, and 17 gametocytes in A. domesticus. About 3 weeks PE, gametocytes disappeared from the peripheral circulation and were not observed again during the autumn, winter, and spring in birds kept in the laboratory.Haematocrit determinations in the Canada geese revealed a low fluctuating anemia during the primary infection which subsided by day 21 PE. A more severe anemia was recorded in A. domesticus with a mean low packed RBC value of about 18% on day 11 PE. Immature and mature hepatic schizonts were observed in the Canada and domestic geese between days 3 and 8 PE. Neither megaloschizonts nor elongate gametocytes were seen. Clinical signs, pathology, and mortality commonly associated with L. simondi infection in ducks were not observed. Hypotheses are advanced to explain reports of severe pathogenesis associated with L. simondi infections in Canada geese in other localities.

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