Life Span Of Erythrocytes Research Articles

A-100 Clinical Utility of Measuring Creatine Concentration in Erythrocyte

Abstract Background Shortened erythrocyte lifespan characterizes hemolytic anemia and impacts HbA1c values. Recently, erythrocyte creatine concentration (EC) measurement emerged as a new method to assess erythrocyte lifespan. However, literature reports conflicting findings regarding the association between erythrocyte lifespan and EC concentration. In our study, we noted low EC concentrations in renal diseases, typically linked to short erythrocyte lifespan, while iron deficiency anemia exhibited high EC concentrations. This contradicts established relationships, prompting a reevaluation of EC concentration assessment. The aim is to evaluate the clinical utility of EC concentration measurements by correlating them with various clinical parameters, including hematopoietic status. Methods EC concentrations were measured in 522 subjects (252 females, 270 males) aged 19 to 95 at Kawasaki Medical School Hospital. Medical records and laboratory test results from around one month before and after blood collection were used to create a database. Box-and-whisker plots illustrated EC concentration distribution for each disease, and scatter plots compared EC concentrations with laboratory parameters. Results EC concentrations were lower in renal diseases like Diabetes and Chronic Kidney Disease but higher in iron deficiency anemia (Fig. 1). Moreover, EC concentrations rose as hemoglobin concentrations declined, unaffected by CKD grade (Fig. 2). Conclusions While conventionally, high EC concentrations imply a short erythrocyte lifespan, our study noted the opposite trend. EC concentrations might not indicate erythrocyte lifespan but instead reflect hemoglobin synthesis. Investigating EC concentration's relationship with factors like iron and vitamin B12 involved in hemoglobin synthesis may unveil new clinical applications.

Vaccine enhancement and improved immunogenicity using erythrocytes as carriers

Achieving optimal immunogenicity and efficacy in vaccination presents significant challenges, including the need for multiple doses and the limited immunogenicity observed with certain vaccine formulations. To overcome these obstacles, researchers are exploring supplementary components and innovative delivery strategies. The development of an effective vaccine delivery technology is crucial for achieving sufficient protective immunity and disease prevention. This article focuses on the potential of erythrocytes as vaccine carriers to enhance vaccine effectiveness, particularly in the context of whole particle vaccines. The extended lifespan of erythrocytes enables sustained antigen exposure, resulting in continuous antigen presentation to immune cells. Moreover, erythrocytes exhibit biocompatibility, a well-established safety profile, and the capacity to modulate immune responses through interactions with complement receptors. These characteristics position erythrocytes as an appealing platform for targeted vaccine delivery. The hypothesis suggests utilizing bispecific monoclonal antibodies to complement receptor 1 and specific pathogen proteins to hitchhike inactivated pathogens onto erythrocytes. These modified erythrocytes can then serve as carriers to deliver the whole particle vaccine to antigen-presenting cells (APCs) or function as APCs themselves in the spleen. This article puts forward treatment protocols aimed at improving accessibility of vaccinations at the appropriate location, reducing the frequency of vaccine doses, and stimulating sufficient protective immunity.

Adaptive selection at G6PD and disparities in diabetes complications.

Diabetes complications occur at higher rates in individuals of African ancestry. Glucose-6-phosphate dehydrogenase deficiency (G6PDdef), common in some African populations, confers malaria resistance, and reduces hemoglobin A1c (HbA1c) levels by shortening erythrocyte lifespan. In a combined-ancestry genome-wide association study of diabetic retinopathy, we identified nine loci including a G6PDdef causal variant, rs1050828 -T (Val98Met), which was also associated with increased risk of other diabetes complications. The effect of rs1050828 -T on retinopathy was fully mediated by glucose levels. In the years preceding diabetes diagnosis and insulin prescription, glucose levels were significantly higher and HbA1c significantly lower in those with versus without G6PDdef. In the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial, participants with G6PDdef had significantly higher hazards of incident retinopathy and neuropathy. At the same HbA1c levels, G6PDdef participants in both ACCORD and the Million Veteran Program had significantly increased risk of retinopathy. We estimate that 12% and 9% of diabetic retinopathy and neuropathy cases, respectively, in participants of African ancestry are due to this exposure. Across continentally defined ancestral populations, the differences in frequency of rs1050828 -T and other G6PDdef alleles contribute to disparities in diabetes complications. Diabetes management guided by glucose or potentially genotype-adjusted HbA1c levels could lead to more timely diagnoses and appropriate intensification of therapy, decreasing the risk of diabetes complications in patients with G6PDdef alleles.

Testosterone and Erythrocyte Lifespan.

Endogenous and exogenous androgens increase circulating erythrocytes and hemoglobin but their effects on erythrocyte lifespan is not known. To investigate androgen effects on immature and mature erythrocyte lifespan in humans and mice using novel non-radioactive minimally invasive methods. Human erythrocyte lifespan was estimated using alveolar carbon monoxide concentration and blood hemoglobin in Levitt's formula in hypogonadal or transgender men before and up to 18 weeks after commencing testosterone (T) treatment. Erythrocyte lifespan was estimated in androgen receptor (AR) knockout and wild-type mice after T or dihydrotestosterone (DHT) treatment of intact females or orchidectomized males using in vivo biotin labelling of erythrocyte surface epitopes for reticulocytes (Ter119+CD71+) and two markers of erythrocytes (CD45-, Ter119+CD71-) monitoring their blood disappearance rate by flow cytometry. Before treatment, hypogonadal and transgender men had marked reduction in erythrocyte lifespan compared with controls. T treatment increased erythrocyte lifespan at 6 weeks but returned to pre-treatment levels at 18 weeks while serum T and blood hemoglobin were increased by T treatment remaining elevated at 18-weeks. In mice T and DHT treatment had higher erythrocyte (but not reticulocyte) lifespan but neither orchidectomy nor AR inactivation significantly influenced erythrocyte or reticulocyte lifespan. We conclude that hypogonadal men have reduced erythrocyte lifespan and acute androgen-induced increase in circulating erythrocyte lifespan may contribute to the well-known erythropoietic effects of androgens, but longer-term effects require further investigation to determine how much they contribute to androgen-induced increases in circulating hemoglobin.

Mechanisms and Cardiorenal Complications of Chronic Anemia in People with HIV.

Chronic anemia is more prevalent in people living with HIV (PLWH) compared to the general population. The mechanisms that drive chronic anemia in HIV are multifaceted and include functional impairment of hematopoietic stem cells, dysregulation of erythropoietin production, and persistent immune activation. Chronic inflammation from HIV infection adversely affects erythropoiesis, erythrocyte lifespan, and erythropoietin response, leading to a heightened risk of co-infections such as tuberculosis, persistent severe anemia, and increased mortality. Additionally, chronic anemia exacerbates the progression of HIV-associated nephrotoxicity and contributes to cardiovascular risk through immune activation and inflammation. This review highlights the cardinal role of chronic inflammation as a link connecting persistent anemia and cardiovascular complications in PLWH, emphasizing the need for a universal understanding of these interconnected pathways for targeted interventions.

Biochemical and biophysical characterization of hemoglobin of erythrocytes from patients suffering from iron deficiency anemia: A pilot study.

Background: Iron deficiency anemia (IDA) is a substantial global health concern, affecting nearly 1 billion individuals worldwide, and women are the more vulnerable due to their various reproductive phases. This study examines physicochemical aspects of erythrocytes in IDA women, especially in reproductive-age women in the North 24 Parganas district of West Bengal. Methods: Fifteen IDA women and eight healthy women aged 25 to 45 years were selected, and only ten volunteers fulfilled the IDA criteria. Observations: Scanning electron microscopic study revealed the formation of echinocytes, indicating asymmetry in the lipid bilayer of the erythrocyte membrane. Although native-PAGE did not show any remarkable change in hemoglobin structure, absorption spectra indicated structural abnormality in the globin chain of hemoglobin. Increased methemoglobin (metHb) formation rate (higher co-oxidation rate) and increased metHb content in the membrane-bound hemoglobin are clear indications of the alteration of physicochemical property of hemoglobin, which may affect erythrocyte life span in IDA. Conclusion: The hemoglobin of IDA individuals is not only quantitatively low, but the quality is also compromised by its structure, and the morphology of erythrocytes is also altered.

Red cell membranopathies: Case series and review of literature

Inherited disorders affecting the red blood cell (RBC) membrane result from mutations in membrane or skeletal proteins. Such mutations can impede red cell deformability, leading to a shortened lifespan and early removal of erythrocytes from circulation. This, in turn, results in anemia and jaundice. Hereditary spherocytosis (HS), hereditary elliptocytosis, hereditary ovalocytosis, and hereditary stomatocytosis are examples of these disorders, with HS being the most prevalent form of inherited hemolytic anemia. Disorders of the RBC membrane may stem from structural or transport functional changes, but they inevitably lead to clinical symptoms of hemolytic anemia. Accurate diagnosis is crucial to avoid complications or inappropriate treatment as management varies depending on pathophysiology. In this review, we describe few cases of different types of RBC membrane disorders with variable age of presentation, emphasizing the significance of correct approach, limitations of certain investigations and the need for genetic test to reach a precise diagnosis.

Bufalin reprograms erythrocyte lifespan through p38 MAPK and Rac1 GTPase

Ample evidence indicates that bufalin (BFN), a cardiotonic steroid in Bufo toad toxin, possesses a potent anticancer activity mainly by stimulating apoptosis in cancer cells. Human red blood cells (RBCs) undergo eryptosis which contributes to a plethora of pathological conditions. No reports, however, have examined the potential toxicity of BFN to RBCs. This study aims to characterize the biochemical mechanisms governing the influence of BFN on the physiology and lifespan of RBCs.Isolated RBCs from healthy volunteers were exposed to anticancer concentrations of commercially available BFN from the skin of Bufo gargarizans (10–200 μM) for 24 h at 37 °C. Photometric assays were used to estimate hemolysis and hemolytic markers, and flow cytometry was used to detect eryptotic markers. Phosphatidylserine externalization was captured by fluorescein isothiocyante-labeled annexin V, cellular dimensions by light scatter patterns, and intracellular Ca2+ and reactive oxygen species (ROS) by fluorogenic dyes Fluo4/AM and 2′,7′-dichlorodihydrofluorescein diacetate (H2DCFDA), respectively. BFN caused Ca2+-independent hemolysis and release of LDH, AST, CK, and K+, and increased annexin V-bound cells, cytosolic Ca2+, cell shrinkage, and ROS levels. BFN also disrupted Na+ and Mg2+ trafficking, and was sensitive to PEG 8000, sucrose, SB203580, and NSC 23766. In whole blood, BFN depleted hemoglobin stores, increased fragmented RBCs, and was selectively toxic to reticulocytes, lymphocytes, and platelets. In conclusion, BFN elicits premature RBC death, subject to regulation by p38 MAPK and Rac1 GTPase, and is detrimental to other peripheral blood cells. Altogether, these novel findings prompt cautious consideration of the toxin in anticancer therapy.

A secretory protein neudesin regulates splenic red pulp macrophages in erythrophagocytosis and iron recycling

Neudesin, originally identified as a neurotrophic factor, has primarily been studied for its neural functions despite its widespread expression. Using 8-week-old neudesin knockout mice, we elucidated the role of neudesin in the spleen. The absence of neudesin caused mild splenomegaly, shortened lifespan of circulating erythrocytes, and abnormal recovery from phenylhydrazine-induced acute anemia. Blood cross-transfusion and splenectomy experiments revealed that the shortened lifespan of erythrocytes was attributable to splenic impairment. Further analysis revealed increased erythrophagocytosis and decreased iron stores in the splenic red pulp, which was linked to the upregulation of Fcγ receptors and iron-recycling genes in neudesin-deficient macrophages. In vitro analysis confirmed that neudesin suppressed erythrophagocytosis and expression of Fcγ receptors through ERK1/2 activation in heme-stimulated macrophages. Finally, we observed that 24-week-old neudesin knockout mice exhibited severe symptoms of anemia. Collectively, our results suggest that neudesin regulates the function of red pulp macrophages and contributes to erythrocyte and iron homeostasis.

THU337 Fructosamine As A Predictor Of Diabetic Microvascular Disease In A Population With High Prevalence Of Red Cell Disorders

Abstract Disclosure: A.J. Buckley: None. T. Ashraf: None. M. Iqbal: None. Background: Fructosamine, glucose bound to circulating proteins, is used to evaluate glycaemic control where HbA1c may be unreliable due to variant haemoglobin or altered erythrocyte lifespan. In previous reports fructosamine predicted prevalent diabetic retinopathy, incident cardiovascular disease, and incident CKD3, in populations where it was highly correlated with HbA1c (r=0.80). Consequently in clinical practice fructosamine is converted to estimated HbA1c for interpretation. Use of fructosamine to estimate microvascular risk in populations where it correlates poorly with HbA1c remains unexplored. Aim: To provide evidence-based estimates for risk of incident retinopathy and early diabetic nephropathy according to a single fructosamine reading. Methods: The study population was 1571, predominantly Arab Emirati, individuals managed at Imperial College London Centre Abu Dhabi and Al Ain (60 prediabetes, 161 T1DM, 1350 T2DM), where a clinician suspected that HbA1c (Variant II ion-exchange HLPC, Bio-Rad), was inaccurate. Fructosamine was measured using the Cobas c501 module (Roche) and divided into strata of <250, 250-299, 300-349, 350-399 and ≥400 µmol/L for analysis. Routine yearly digital retinal screening and urinary albumin:creatinine ratio, and results of haematological investigations, were retrieved from electronic records. Results: Fructosamine was weakly associated with HbA1c (r2 = 0.353, p < 0.0001), with both slope and intercept for the relationship significantly varying according to coexisting haemoglobin variant, G6PD deficiency, iron deficiency, or renal impairment. Adjusted for age, systolic BP and smoking status, all fructosamine strata ≥ 300 µmol/L were significantly associated with stepwise increased hazard of new incident retinopathy for each stratum (300-349 µmol/L 2.1 (1.29-3.30) p=0.003; ≥400 µmol/L 3.3 (1.89-5.6) p <0.001), compared with individuals with fructosamine < 250 µmol/L, over mean follow-up of 2.4 ± 1.6 years. Adjusting for age and systolic BP, fructosamine strata ≥ 300 µmol/L were similarly associated with stepwise significant increased hazard of new incident microalbuminuria (300-349 µmol/L 1.40 (1.11-1.8) p=0.005; ≥ 400 µmol/L 2.3 (1.68-3.00) p <0.001). In 746 individuals with HbA1c <7.0% at inclusion, fructosamine strata ≥300 µmol/L remained significantly associated with increased hazard of retinopathy (300-349 µmol/L 2.10 (1.21-1.3.70) p=0.008; ≥ 400 µmol/L 3.6 (1.50-8.80) p=0.004) but not microalbuminuria. Conclusions: Fructosamine ≥ 300 µmol/L is associated with significantly increased hazard of microvascular complications of diabetes in a population with high incidence of haemoglobin variants and G6DP deficiency, even among individuals apparently achieving conventional HbA1c targets. Routine measurement of at least one fructosamine level to refine treatment targets is supported in such populations. Presentation: Thursday, June 15, 2023

Prediction of Severe Esophageal Varices in Patients With Cirrhosis Based on Levitt's CO Breath Test: A Proof of Concept Study.

This study investigated the feasibility of using erythrocyte (RBC) lifespan determined by Levitt's CO breath test (LCOBT) to predict esophageal varices needing treatment (VNT) in patients with cirrhosis. Esophageal varix bleeding is a common fatal complication of cirrhosis and portal hypertension. The gold standard for identifying VNT is esophagogastroduodenoscopy (EGD), an invasive procedure with low patient compliance. VNT screening based on Baveno VI criteria has mediocre specificity. RBC lifespan was determined by LCOBT in 53 cirrhotic patients (13 without varices, 11 mild/moderate varices, and 29 severe varices). Correlation of varix severity with RBC lifespan and other variables was analyzed. Rates of shortened RBC lifespan and thrombocytopenia (Baveno VI criteria) were compared. RBC lifespan correlated inversely with severity of varices (r=-0.793, P<0.001). Mean RBC lifespans were 129±31, 96±21, and 59±21 days for Nonvarix, Mild/Moderate, and Severe groups. Shortened RBC lifespan (<75d) was observed in 79.3% (23/29) of patients with severe varices, a frequency similar or identical to thrombocytopenia rates [original Baveno VI criteria, 86.2% (25/29), P=0.487; expanded criteria, 79.3% (23/29), P>0.999]. Among 24 patients without severe varices, shortened RBC lifespan was observed in 1 patient whereas thrombocytopenia was detected in 13 and 8 patients based on the original (P<0.001) and expanded criteria (P=0.010), respectively. RBC lifespan correlates inversely with varix severity in patients with cirrhosis. LCOBT may enable specific screening for VNT.

Measurement of Erythrocyte Lifespan Using a CO Breath Test in Patients with Thalassemia and the Impact of Treatment.

Background: Thalassemia comprises a diverse group of genetic disorders that affects the synthesis of globin chains, with a global distribution. The use of erythrocyte lifespan (ELS) to assess differences among patients with different types of thalassemia and the efficacy of splenectomy has not been implemented.

Fructosamine as a predictor of incident diabetic microvascular disease in a population with high prevalence of red cell disorders: A cohort study

AimsFructosamine can be used to estimate glycaemia in individuals in whom HbA1c may be unreliable. We aimed to establish clinically useful fructosamine treatment targets in a population with a high prevalence of conditions affecting erythrocyte survival, including variant haemoglobin and G6PD deficiency. MethodsFructosamine was measured on a clinical basis in individuals in whom HbA1c was suspected to be unreliable by their primary physician. Study endpoints were incident retinopathy and albuminuria in individuals with Prediabetes (n = 60), Type 1 (n = 161) or Type 2 diabetes (n = 1350) during follow up of 4.4 ± 2.3 years. ResultsFructosamine ≥ 250 umol/L was significantly associated with incident retinopathy, and fructosamine ≥ 300 umol/L with incident microalbuminuria, in univariate analysis and adjusted for established risk factors. Fructosamine ≥ 250 umol/L was also significantly associated with incident retinopathy in individuals with HbA1c < 7.0% (53 mmol/mol) at inclusion. ConclusionsIn this patient population, a single measurement of fructosamine significantly and independently predicts incident retinopathy in individuals with HbA1c < 7.0% (53 mmol/mol). Routine measurement of fructosamine on at least one occasion is recommended as part of assessment of prediabetes or diabetes mellitus in populations with a high prevalence of conditions affecting erythrocyte lifespan.

A "Gold Standard" Test for Diagnosing and Quantifying Hemolysis in Neonates and Infants.

Identifying "gold standard" diagnostic tests can promote evidence-based neonatology practice. Hemolysis is a pathological shortening of the erythrocyte lifespan, differing from erythrocyte senescence in responsible mechanisms and clinical implications. Diagnosing hemolysis goes beyond a binary (yes vs. no) determination. It is characterized according to magnitude, and as acute vs. chronic, and genetically based vs. not. For neonates with significant hyperbilirubinemia or anemia, detecting hemolysis and quantifying its magnitude provides diagnostic clarity. The 2022 American Academy of Pediatrics (AAP) Clinical Practice Guideline on management of hyperbilirubinemia in the newborn states that hemolysis is a risk factor for developing significant hyperbilirubinemia and neurotoxicity. The guideline recommends identifying hemolysis from any cause, but specific guidance is not provided. A spectrum of laboratory tests has been endorsed as diagnostic methods for hemolysis. Herein we examine these laboratory tests and recommend one as the "gold standard" for diagnosing and quantifying hemolysis in neonates and infants.

Erythroferrone exacerbates iron overload and ineffective extramedullary erythropoiesis in a mouse model of β-thalassemia.

β-thalassemia is characterized by chronic hepcidin suppression and iron overload, even in patients who have not undergone transfusion. The HbbTh3/+ (Th3/+) mouse model of nontransfusion-dependent β-thalassemia (NTDBT) partially recapitulates the human phenotype but lacks chronic hepcidin suppression, progressive iron accumulation into adulthood, or the interindividual variation of the rate of iron loading observed in patients. Erythroferrone (ERFE) is an erythroid regulator that suppresses hepcidin during increased erythropoiesis. ERFE concentrations in the sera of patients with NTDBT correlate negatively with hepcidin levels but vary over a broad range, possibly explaining the variability of iron overload in patients. To analyze the effect of high ERFE concentrations on hepcidin and iron overload in NTDBT, we crossed Th3/+ mice with erythroid ERFE-overexpressing transgenic mice. Th3/ERFE-transgenic mice suffered high perinatal mortality, but embryos at E18.5 showed similar viability, appearance, and anemia effects as Th3/+ mice. Compared with Th3/+ littermates, adult Th3/ERFE mice had similarly severe anemia but manifested greater suppression of serum hepcidin and increased iron accumulation in the liver, kidney, and spleen. The Th3/ERFE mice had much higher concentrations of serum ERFE than either parental strain, a finding attributable to both a higher number of erythroblasts and higher production of ERFE by each erythroblast.Th3/+ and Th3/ERFE mice had similar red blood cell count and shortened erythrocyte lifespan, but Th3/ERFE mice had an increased number of erythroid precursors in their larger spleens, indicative of aggravated ineffective extramedullary erythropoiesis. Thus, high ERFE concentrations increase the severity of nontransfusional iron overload and ineffective erythropoiesis in thalassemic mice but do not substantially affect anemia or hemolysis.

#3627 PHOSPHATIDYLSERINE EXPOSURE AND SHORTENED LIFE SPAN OF ERYTHROCYTES IN RENAL ANEMIA

Abstract Background and Aims The lifespan of erythrocytes in patients with renal anemia is shortened (∼70 days) compared to that of healthy erythrocytes (120 days), but the pathological mechanisms and causes are unclear. Senescent erythrocytes express phosphatidylserine (PS) on their outer membrane, which is a signal for being removed by macrophages. The PS localization in the cellular membrane is mainly regulated by two transporters: flippases and scramblases. Flippases, type Ⅳ P-type ATPases (P4-ATPases), maintain PS localization in the inner leaflet by transporting PS from the outer leaflet of the cell membrane. When scramblases are activated, they facilitate equal distribution of phospholipids between the inner and outer lipid bilayers, resulting in the exposure of PS on the outer leaflet. Recently, we have revealed that reduced flippase activity contributes to PS exposure in healthy senescent erythrocytes [1]. In this study, we examined the percentage of PS-exposed cells and the transporter activity in erythrocytes from renal anemia to elucidate the mechanism of the shortened lifespan. Method This study was approved by the Ethics Committee of Tokyo Women's Medical University (#3835, #4822R2). Erythrocytes from the renal anemic patients undergoing maintenance hemodialysis were separated with the centrifugation using Percoll-density gradient according to our previous report. Resultant heavy and light fractions were used as senescent and young erythrocytes, respectively. We analyzed the percentage of PS-exposed cells (n = 12), flippase/scramblase activities (n = 7), and the factors involved in those enzymatic activities such as intracellular K+ (n = 10) and ATP concentration (n = 9). We also measured protein 4.1a/b and HbA1c as an index of erythrocytes’ age. Results The cells from renal anemia were separated to heavy (senescent) and light (young) fractions, which was similar to the distributions previously performed on healthy erythrocytes. The PS-exposed erythrocytes in the heavy fraction were slightly more than those of the light fraction (p &amp;lt; 0.01, Wilcoxon test), and the flippase activity of the heavy fraction decreased more than that of the light fraction (p &amp;lt; 0.01, paired t-test). Intracellular K+ concentration decreased in the heavy fraction more than in the light fraction similar to the healthy senescent erythrocytes, but there was no statistical difference in the intracellular ATP concentration between the heavy and light fractions. The measurement of protein 4.1a/b and HbA1c in these fractions is still in progress. Conclusion Similar to healthy erythrocytes, reduced flippase activity contributes to PS exposure in senescent erythrocytes of renal anemia, maybe due to the decreased intracellular K+ concentration. This may occur in an earlier stage of senescence than the healthy ones, which may explain the mechanism of the shortened life span.

Comparative evaluation of clinical glycemic control markers treated with imeglimin and its effect on erythrocytes in patients with type 2 diabetes mellitus: study protocol of a single-arm, open-label, prospective, exploratory trial.

Background: Imeglimin is a novel type 2 diabetes (T2D) drug that is expected to improve mitochondrial function. In its phase 3 clinical trials in Japanese patients with T2D, the hemoglobin A1c (HbA1c) decrease following imeglimin administration was slow, reaching a plateau after 20-24weeks of treatment. In general, the erythrocyte lifespan may be a factor when HbA1c shows an abnormal value. Therefore, this study will comparatively evaluate HbA1c and other markers of glycemic control in patients with T2D after imeglimin administration and also examine the effects of imeglimin on erythrocytes. Methods: This single-arm, open-label, prospective, exploratory study is designed to evaluate the divergence between HbA1c and glycoalbumin (GA) or 1,5-anhydroglucitol (1,5-AG) and the glycemic reduction rate in 30 patients with T2D with inadequate glycemic control when imeglimin 2,000mg is administered for 6months. In addition, we will examine the effect on erythrocytes, the presumed cause of this divergence. We will measure sustained glycemic variability using flash glucose monitoring and examine the relationship between changes in these indices and HbA1c. Moreover, because prolonged erythrocyte lifespan is a possible cause of falsely high HbA1c levels, erythrocyte lifespan, erythrocyte deformability, and hemoglobin concentration will be evaluated as effects of imeglimin on erythrocytes. Furthermore, if imeglimin has an ameliorative effect on erythrocyte deformability, it may improve peripheral arterial disease; thus, we will also evaluate the toe-brachial pressure index, a measure of this effect. Discussion: In this study, if imeglimin administration results in diverging rates of hypoglycemic effect between HbA1c and GA or 1,5-AG and prolongs erythrocyte lifespan, GA and 1,5-AG, rather than HbA1c, will be considered appropriate measures of the hypoglycemic effect in the early stages of imeglimin administration. If imeglimin improves erythrocyte deformability, it may also be a new treatment strategy for peripheral arterial disease, a chronic complication of T2D. Ethics and dissemination: The study protocol was scientifically and ethically reviewed and approved by the Certified Clinical Research Review Board of Toho University (approval number: THU22002). The study protocol was registered in the Japan Registry of Clinical Trials (jRCT) in December 2022 (jRCTs031220489).

Pengaruh Pemberian Ekstrak Okra (Abelmoschus Esculentus) terhadap Peningkatan Jumlah Eritrosit dan Kadar Hemoglobin (Hb) Darah Tikus Putih Jantan (Rattus Norvegicus) Anemia yang Diinduksi Natrium Nitrit (NaNO2)

Hemolytic anemia is a condition which the number of erythrocytes and hemoglobin levels are less than normal due to shortening of life span, rupture and destruction of erythrocytes. One of the factors causing the rupture and destruction of erythrocytes is oxidative stress. Okra contain flavonoid antioxidants that can counteract and prevent oxidative stress. This research to determine the effectiveness of okra (Abelmoschus Esculentus) extract on increasing the number of erythrocytes and hemoglobin (Hb) levels in the blood of anemia male white rats (Rattus Norvegicus) induced by sodium nitrite (NaNO2). Experiment with Posttest Only Control Group Design was held. The number of samples used were 24 male white rats (Rattus norvegicus) which were divided into 4 groups; the positive control group, which was only given NaNO2 and the other three groups were given NaNO2 and okra extract (Abelmoschus Esculentus) at 200mg/kgBW/day, 300mg/kgBW/day, and 400mg/kgBW/day for 28 days. Blood samples were taken and then the number of erythrocytes and hemoglobin levels were calculated using a hematoanalyzer. Anova test results obtained a significant value (sig, 0.000) between groups. Okra (Abelmoschus Esculentus) extract was able to increase the number of erythrocytes and hemoglobin (Hb) levels. Okra (Abelmoschus Esculentus) extract has an effect on increasing the number of erythrocytes and blood hemoglobin levels of anemic male white rats.

Changes and clinical significance of erythrocyte lifespan in megaloblastic anemia

Objective: To investigate the lifespan of erythrocytes in megaloblastic anemia (MA) patients. Methods: A prospective cohort study analysis. Clinical data from 42 MA patients who were newly diagnosed at the Department of Hematology, Lanzhou University Second Hospital from January 2021 to August 2021 were analyzed, as were control data from 24 healthy volunteers acquired during the same period. The carbon monoxide breath test was used to measure erythrocyte lifespan, and correlations between erythrocyte lifespan and laboratory test indexes before and after treatment were calculated. Statistical analysis included the t-test and Pearson correlation. Results: The mean erythrocyte lifespan in the 42 newly diagnosed MA patients was (49.05±41.60) d, which was significantly shorter than that in the healthy control group [(104.13±42.62) d; t=5.13,P=0.001]. In a vitamin B12-deficient subset of MA patients the mean erythrocyte lifespan was (30.09±15.14) d, and in a folic acid-deficient subgroup it was (72.00±51.44) d, and the difference between these two MA subsets was significant (t=3.73, P=0.001). The mean erythrocyte lifespan after MA treatment was (101.28±33.02) d, which differed significantly from that before MA treatment (t=4.72, P=0.001). In MA patients erythrocyte lifespan was positively correlated with hemoglobin concentration (r=0.373), and negatively correlated with total bilirubin level (r=-0.425), indirect bilirubin level (r=-0.431), and lactate dehydrogenase level (r=-0.504) (all P<0.05). Conclusions: Erythrocyte lifespan was shortened in MA patients, and there was a significant difference between a vitamin B12-deficient group and a folic acid-deficient group. After treatment the erythrocyte lifespan can return to normal. Erythrocyte lifespan is expected to become an informative index for the diagnosis and treatment of MA.

New Clues to Cardiovascular Disease: Erythrocyte Lifespan.

Determination of erythrocyte lifespan is an important part of the diagnosis of hemolytic diseases. Recent studies have revealed alterations in erythrocyte lifespan among patients with various cardiovascular diseases, including atherosclerotic coronary heart disease, hypertension, and heart failure. This review summarizes the progress of research on erythrocyte lifespan in cardiovascular diseases.