Life Span Of Erythrocytes Research Articles

A pilot study: effect of erythrocyte lifespan determined by a modified carbon monoxide breath test on glycosylated hemoglobin interpretation

Glycosylated hemoglobin (HbA1c) is an important criterion for the diagnosis of diabetes and an indicator of the blood glucose level. The red blood cell (RBC) lifespan heterogeneity is sufficient to influence the HbA1c interpretation. In this study, we recruited 120 patients with diabetes mellitus and 85 nondiabetic controls. The HbA1c and the RBC lifespan were detected by high-performance liquid chromatography and the advanced carbon monoxide breath detection method, respectively. Potential correlations of gender and age with HbA1c were analyzed and a receiver operator characteristic curve was generated to get the HbA1c cut-off for every RBC lifespan group. It was confirmed that HbA1c has no correlation with gender or age. The correlation formula between the HbA1c diagnostic criteria and RBC lifespan was derived to correct the HbA1c diagnostic criteria using the least-square method. The RBC-lifespan-corrected HbA1c diagnostic criteria provided 100% sensitivity and specificity for the diagnosis of diabetes in the experimental set and was not refuted in the validated set. The diagnostic value of HbA1c is positively correlated with the RBC lifespan, and four patients with hyperglycemia, whose HbA1c values were lower than the general diagnosis criterion of 6.5%, were still considered to be diabetic according to this formula; that is, the application of this formula may help us to eliminate the 2.2% misdiagnosis rate of the current diagnostic criteria. To provide more accurate detection results, the effect of the RBC lifespan needs to be taken into account when HbA1c is used as a clinical indicator.

Acetaldehyde-induced oxidative modifications and morphological changes in isolated human erythrocytes: an in vitro study.

Acetaldehyde is a toxic, mutagenic and carcinogenic metabolite of alcohol which can bind to proteins, DNA and several other cellular macromolecules. Chronic alcohol consumption increases intracellular acetaldehyde levels which enhances the generation of reactive oxygen and nitrogen species (ROS and RNS). In this study, we have examined the effect of acetaldehyde on human erythrocytes under in vitro conditions. Treatment of human erythrocytes with different concentrations of acetaldehyde (0.05-2mM) for 24h at 37°C increased intracellular generation of ROS and RNS. It also increased oxidation of proteins and lipids but decreased glutathione, total sulphhydryl and free amino group content. Methemoglobin level was increased accompanied by a decrease in methemoglobin reductase activity. Acetaldehyde impaired the antioxidant defence system and lowered the total antioxidant capacity of the cell. It decreased the activity of metabolic and membrane-bound enzymes and altered erythrocyte morphology. Our results show that acetaldehyde enhances the generation of ROS and RNS that results in oxidative modification of cellular components. This will lower the oxygen transporting ability of blood and shorten erythrocyte lifespan (red cell senescence).

Band 3 ectopic expression in colorectal cancer induces an increase in erythrocyte membrane-bound IgG and may cause immune-related anemia.

Autoimmune hemolytic anemia (AIHA) is a rare comorbidity in colorectal cancer (CRC) and has an unknown etiology. Previously, we described an AIHA case secondary to CRC with ectopic band 3 expression. Herein, we investigated ectopic band 3 expression and erythrocyte membrane-bound IgG in a CRC cohort. Between September 2016 and August 2018, 50 patients with CRC and 26 healthy controls were enrolled in the present study. The expression of band 3 and SLC4A1 mRNA was observed in 97% of CRC surgical specimens. Although clinical AIHA was not observed in any patient with CRC, a direct antiglobulin test was positive in 10 of the patients in the CRC group (p = 0.01). Flow cytometry revealed significantly increased erythrocyte membrane-bound IgG among patients with CRC compared to healthy controls (mean ± standard deviation; 38.8 ± 4.7 vs. 29.9 ± 15.6, p = 0.012). Normocytic anemia was observed, including in cases negative for fecal occult blood, suggesting a shortened erythrocyte life-span due to increased membrane-bound IgG. Immunoprecipitation revealed increased anti-band 3 autoantibodies in patients' sera. Mouse experiments recapitulated this phenomenon. We also confirmed that band 3 expression is controlled by 5'AMP-activated protein kinase under hypoxic conditions. These findings increase our understanding of the etiology of cancer-related anemia.

The pathogenesis of anemia in inflammation

Inflammation is a physiological process that primarily occurs as a way to help protect the host against tissue damage and invasion by pathogens. During inflammation, erythropoiesis is suppressed and, if it lasts, anemia develops. The mechanisms underlying this are complex and not fully understood, but various cytokines, such as tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), interleukin-1β (IL-1β), and IL-6, are involved. TNF-α upregulates PU.1, which is a crucial transcription factor in granulocytic differentiation, and downregulates GATA-1, a master transcription factor for erythroid differentiation, in hematopoietic stem cells. TNF-α and IL-1β suppress erythropoietin production in the kidney, whereas IFN-γ downregulates the expression of erythropoietin receptors in erythroid precursor cells. Moreover, IL-6 upregulates the production of hepcidin, the master regulator of systemic iron metabolism, in the liver. Hepcidin reduces the iron available for erythropoiesis by downregulating the rate of iron release from macrophages. Activated macrophages may also contribute to the development of anemia by shortening the erythrocyte lifespan. Proper management of the underlining conditions is necessary in treating anemia associated with inflammation. Erythropoiesis-stimulating agents may be administered to patients with chronic kidney disease, whereas anti-IL-6 agents may be beneficial for anemic patients with rheumatoid arthritis and idiopathic multicentric Castleman disease.

Iron Restriction Improves Markers of Disease Severity in the Townes Mouse Model of Sickle Cell Anemia

Introduction: Sickle cell anemia (SCA) is caused by mutations in β-globin that result in the production of the abnormal hemoglobin, HbS, with deleterious effects on erythrocyte shape and life span. Because the propensity of erythrocytes to sickle is inversely proportional to the concentration of HbS in the cell, decreasing the mean cellular hemoglobin concentration (MCHC) represents a potential therapeutic approach. Whereas iron restriction in healthy individuals does not alter MCHC, concomitant iron deficiency has been associated with decreased MCHC in SCA patients. Isolated case reports have linked iron restricted erythropoiesis with decreased hemolysis, increased red cell lifespan, and improvement in certain outcomes in SCA patients. We systematically examined the effects of iron restriction on erythropoietic outcomes in SCA utilizing the Townes murine model to investigate the hypothesis that mice with dietary iron deficiency will demonstrate a decreased MCHC, decreased erythrocyte sickling propensity, and improved anemia compared with mice on an iron sufficient diet. Methods: Townes SCA mice were weaned to diets containing either 20 ppm iron (low) or 48 ppm iron (sufficient) and maintained on those diets until sacrifice at 2 months of age. Blood was collected for complete blood count by submandibular or cardiac puncture. Spleen weight was normalized to body weight for calculation of the splenic index. Red cell deformability, defined by the elongation index (EI), and the oxygen pressure at which sickling occurs (point of sickling) during deoxygenation were characterized by oxygenscan ektacytometry using a laser optical rotational red cell analyzer (Mechatronics, The Netherlands). Results: SCA mice fed a 20 ppm low iron diet demonstrate a significant decrease in MCHC compared to SCA mice fed a 48 ppm iron sufficient diet (17.7+1.1 vs 22.7+5.5 g/dL; p <0.05). Mice fed the low iron diet produced more circulating RBCs (5.98+1.03 vs 4.61+0.84 x 106 cells/uL; p <0.05) and a higher hematocrit (39.4+7.1 vs 24.6+4.6%; p <0.05) with a corresponding decrease in splenic index (0.074+0.14 vs 0.087+0.006 g/g body weight; p <0.05) compared to mice fed the iron sufficient diet. RBCs from mice fed the low iron diet showed a significant decrease in the oxygen pressure at the point of sickling compared to RBCs from mice fed the iron sufficient diet (31.9+4.7 vs 40.6+4.6 mmHg; p <0.01). The low iron diet also resulted in an overall improvement in deformability as evidenced by an increase in the EI minimum compared to the iron sufficient diet (0.25+.07 vs 0.12+.03 au; p <0.01). No significant differences between groups were found in maximum deformability (EI max). The improved EI minimum translates to a decreased change in elongation (Delta EI), defined as EI max minus EI min, in RBCs from mice fed the low iron diet compared to mice fed the iron sufficient diet (0.11+.08 vs .23+.02 au; p <0.01). Conclusions: Decreased dietary iron intake is associated with a decrease in the MCHC in Townes SCA mice. The lower MCHC is accompanied by an amelioration of anemia, decreased extramedullary erythropoiesis, improved RBC deformability and a shift in the initiation of sickling to lower oxygen pressures during deoxygenation. We speculate that iron restriction may decrease the clinical complications arising from both hemolysis and sickling in SCA. Future studies will utilize this model system to further characterize the effects of manipulating iron homeostasis on erythropoietic outcomes in SCA. Disclosures Fleming: Protagonist: Membership on an entity's Board of Directors or advisory committees; Silence Therapeutics: Consultancy; Ultragenyx: Consultancy.

IFN-γ-Dependent Reduction of Erythrocyte Life Span Leads to Anemia during Mycobacterial Infection.

Anemia is a frequent and challenging complication of mycobacterial infections. We used a model of disseminated Mycobacterium avium infection in mice to investigate the mechanisms of mycobacteria-induced anemia. We found increased formation of RBC in the bone marrow and spleen of infected mice. Infection induced reticulocytosis and the premature egress of immature progenitors to the systemic circulation in an IFN-γ (IFNG)-dependent way. The newly formed RBC had reduced CD47 surface expression and a reduced life span and were phagocytosed in the liver of infected mice, increasing iron recycling in this organ. The increased engulfment and degradation of RBC was independent of IFNG sensing by macrophages. Together, our findings demonstrate that mycobacterial infection alters the formation of erythrocytes, leading to their accelerated removal from circulation and hemolytic anemia. This comprehensive elucidation of the mechanisms underlying mycobacteria-induced anemia has important implications for its efficient clinical management.

Effect of compound electrolyte injection on phosphatidylserine exposure in erythrocytes after blood salvage-retransfusion in dogs

Objective To evaluate the effect of compound electrolyte injection on phosphatidylserine (PS) exposure in erythrocytes after blood salvage-retransfusion in dogs. Methods Twenty healthy mongrel dogs, weighing 10-15 kg, aged 3-5 weeks, were divided into 2 groups (n=10 each) using a random number table method: normal saline group (group NS) and compound electrolyte injection group (group MEI). The process of intraoperative blood salvage-retransfusion was simulated in both groups: femoral vein was cannulated for blood withdrawal until the volume of blood lost was 400 ml, and the shed blood was salvaged by a blood recovery machine.The washing solution was normal saline in group NS and compound electrolyte injection in group MEI.The erythrocytes were retransfused after being labeled with fluorescein isothiocyanate.Blood samples were obtained before and after blood salvage for determination of erythrocyte ATP content by enzyme-linked immunosorbent assay.Blood samples were obtained at 24, 48 and 72 h after blood retransfusion, and the PS exposure rate of the salvaged erythrocytes was determined by flow cytometry.The spleen was taken at 72 h after retransfusion to detect the phagocytosis rate of salvaged erythrocytes by monocytes. Results There was no significant difference in ATP content before and after blood salvage between the two groups (P>0.05). Compared with NS group, the PS exposure rate of the salvaged erythrocytes at each time point after retransfusion and phagocytosis rate of salvaged erythrocytes by monocytes were significantly decreased in MEI group (P<0.05). Conclusion Compound electrolyte injection as a washing solution for intraoperative blood salvage can reduce the PS exposure in salvaged erythrocytes and is helpful in prolonging the lifespan of erythrocytes after retransfusion in dogs. Key words: Electrolytes; Erythrocytes; Operative blood salvage; Phosphatidylserines; Monocytes

Current and emerging treatments for sickle cell disease.

Sickle cell disease (SCD) is a group of inherited blood disorders affecting the hemoglobin, shortening the lifespan of erythrocytes, and causing them to take on a distinctive sickled shape that can lead to vaso-occlusion. Current treatment aims to reduce morbidity and mortality through hydroxyurea, erythrocyte transfusion, and hematopoietic stem cell transplantation. This article reviews the disease process, typical presentations, complications, and acute and chronic treatment options.

Spurious HbA1c results in patients with diabetes treated with dapsone.

SummaryMeasurement of glycated haemoglobin (HbA1c) has been utilised in assessing long-term control of blood glucose in patients with diabetes, as well as diagnosing diabetes and identifying patients at increased risk of developing diabetes in the future. HbA1c reflects the level of blood glucose to which the erythrocyte has been exposed during its lifespan, and there are a number of clinical situations affecting the erythrocyte life span in which HbA1c values may be spuriously high or low and therefore not reflective of the true level of glucose control. In the present case series, we describe the particulars of three patients with diabetes who had spuriously low HbA1c levels as a result of dapsone usage. Furthermore, we discuss the limitations of HbA1c testing and the mechanisms by which it may be affected by dapsone in particular.Learning points:Various conditions and medications can result in falsely low HbA1c.Dapsone can lead to falsely low HbA1c by inducing haemolysis and by forming methaemoglobin.Capillary glucose measurement, urine glucose measurements and fructosamine levels should be used as alternatives to HbA1c for monitoring glycaemic control if it was falsely low or high.

Genetic variation influencing hemoglobin levels and risk for anemia across populations.

Hemoglobin (Hb) concentration is the outcome of the interaction between genetic variation and environmental factors, including nutritional status, sex, age, and altitude. Genetic diversity influencing this protein is complex and varies widely across populations. Variants related to abnormal Hb or altered characteristics of the erythrocytes increase the risk for anemia. The most prevalent are related to the inherited globin abnormalities affecting Hb production and structure. Malaria-endemic regions harbor the highest frequencies of variants associated with the most frequent monogenic diseases and the risk for nonnutritional anemia and are considered as public health problems. Variation in genes encoding for enzymes and membrane proteins in red blood cells also influence erythrocyte life span and risk for anemia. Most of these variants are rare. Interindividual variability of hematological parameters is also influenced by common genetic variation across the whole genome. Some of the identified variants are associated with Hb production, erythropoiesis, and iron metabolism. Specialized databases have been developed to organize and update the large body of available information on genetic variation related to Hb variation, their frequency, geographical distribution, and clinical significance. Our present review analyzed the underlying genetic factors that affect Hb concentrations, their clinical relevance, and geographical distribution across populations.

Hemolysis causes a decrease in HbA1c level but not in glycated albumin or 1,5-anhydroglucitol level

HbA1c has been widely used as a glycemic control indicator or as a diagnostic indicator for diabetes mellitus. However, HbA1c is affected by the erythrocyte life span and, therefore, shows falsely low values in hemolytic patients. Erythrocyte creatine (EC) is a sensitive hemolytic marker that reflects the mean erythrocyte age. In the present study, the relationships of HbA1c, glycated albumin (GA), and 1,5-anhydroglucitol (1,5-AG) with different hemolytic markers, including EC, were investigated in non-diabetic individuals. A total of 43 non-diabetic individuals whose complete blood count and reticulocytes were measured via medical examinations were included in this study (28 individuals with hemolysis and 15 individuals without hemolysis). Those with suspected diabetes mellitus based on medical history, low 1,5-AG values, or had comorbid liver and renal diseases were excluded from this study. HbA1c, GA, 1,5-AG, and various hemolytic markers were measured to examine the correlation of the glycemic control indicators with the various hemolytic markers. A significant correlation was observed between GA and 1,5-AG but not between HbA1c and GA or 1,5-AG. Significant correlations were observed between HbA1c values and various hemolytic markers (reticulocytes, haptoglobin, and EC) but not between GA or 1,5-AG values and those hemolytic markers. HbA1c, but not with GA and 1,5-AG, showed significant correlations with the hemolytic markers. These results suggested that HbA1c does not reflect the glycemic control accurately in hemolytic patients, while GA and 1,5-AG values are not affected by mean erythrocyte age and, therefore, accurately reflect the glycemic control.

Epidemiological, biological and clinical update on exercise-induced hemolysis.

Exercise-induced hemolysis can be conventionally defined as rupture and destruction of erythrocytes during physical exercise. The currently available epidemiologic information attests that a substantial degree of exercise-induced hemolysis is commonplace after short-, medium-, long- and ultra-long distance running, as reflected by significant decrease of serum or plasma haptoglobin and significant increase of plasma concentration (or overall blood content) of free hemoglobin. This paraphysiological intravascular hemolysis is typically mild (average variations of hemolysis biomarkers are usually comprised between 1.2- and 1.8-fold), almost self-limiting (completely resolving within 24-48 hours), with severity depending on athlete population, analytical technique used for detecting intravascular hemolysis, as well as on number, frequency and intensity of ground contacts, but not on running technique. Additional lines of evidence support the notion that both osmotic fragility and membrane structure of erythrocytes are considerably modified during endurance exercise. This fact goes hand in hand with findings that erythrocyte lifespan in runners is approximately 40% shorter than in sedentary controls. Direct mechanical injury caused by forceful ground contacts, repeated muscle contractile activity or vasoconstriction in internal organs are three potential sources of exercise-induced hemolysis, whilst metabolic abnormalities developing while exercising (e.g., hyperthermia, dehydration, hypotonic shock, hypoxia, lactic acidosis, shear stress, oxidative damage, proteolysis, increased concentration of catecholamines and lysolecithin) may actively contribute to trigger, accelerate or amplify this phenomenon. Although no systematic evidence is available, it seems also reasonable to hypothesize that patients bearing erythrocyte disorders may be particularly vulnerable to developing exercise-induced hemolysis.

Changes in Serum Lipids from Egg Consumption Are Associated with Clinical Erythrocyte Indices (P08-093-19)

ObjectivesSerum lipids may influence the lifespan of erythrocytes, and have been associated with clinical erythrocyte indices at the population level. Consumption of whole eggs vs. egg whites exerts varying effects on serum lipids and lipoprotein profiles; therefore, we investigated whether egg-induced changes in serum lipids correspond to changes in clinical erythrocyte markers. MethodsYoung, healthy men and women (18–35y, BMI < 30 kg/m2, n = 11) were recruited to participate in an ongoing intervention trial. All subjects followed an egg-free diet for 4 weeks, then were randomized to consume either 3 whole eggs or 3 egg whites per day for 4 weeks. Fasting serum lipids, complete blood cell counts, and dietary intake analysis was performed at the end of each study period. ResultsAverage serum lipids and erythrocyte indices were within normal ranges at the end of each diet period. Changes in total cholesterol following the whole egg (+4.8%) and egg white (0.4%) diet period were not significant as compared to the egg-free diet period. Similarly, clinical erythrocyte markers were not significantly altered by daily consumption of whole eggs or egg whites. However, changes in total cholesterol and LDL-cholesterol between diet periods were positively correlated with changes in total red blood cell counts and hemoglobin. Total cholesterol was additionally correlated with hematocrit levels, and negatively associated with red cell distribution width. Total red blood cell counts and hemoglobin were further correlated with changes in the total cholesterol to HDL-cholesterol ratios, but not HDL-cholesterol alone. ConclusionsOur findings indicate that egg-induced changes in serum lipids are associated with clinical erythrocyte indices, and that total cholesterol levels and dyslipidemia may be more significant determinants of erythrocyte profiles. Funding SourcesThis study was funded by an Agriculture and Food Research Initiative Grant from the USDA National Institute of Food and Agriculture.

Colla corii asini might upregulate ZNF471 and THOC5 by KRAB domain-containing zinc-finger protein pathway and THO complex subunit 5 pathway to improve anemia of pregnant women with β-thalassemia.

Pregnant patients with β-thalassemia are more likely to have progressive anemia which expose them to risk of adverse pregnancy outcomes, blood transfusion, and iron overload. Results from our previous study indicated that Colla corii asini (CCA, E'jiao), a natural ingredient of traditional Chinese medicine, could significantly increase hemoglobin level of pregnant women with β- thalassemia, but the underlying molecular mechanism was unclear. Thus, we applied high-throughput transcriptome sequencing to study the transcriptomic change before and after the CCA treatment. Twenty eligible pregnant women were recruited and randomized to either the CCA treatment group or the blank control group in a 3:1 ratio. Patients in the treatment group orally received daily 15g CCA powder for 4weeks. We analyzed the therapeutic effect indexes and the transcriptomic change in subjects' peripheral blood before and after treatment. We found that β CD 41-42(-TTCT)/βA was the main genotype of the subjects. The regulatory impact of CCA treatment became more evident among the subjects of genotype β CD 41-42(-TTCT)/βA. Gene ontogenesis analysis revealed that the top five molecular functions of differentially expressed genes were involved in membrane functionality and cellular structure. We further identified two consistent upregulated genes ZNF471 and THOC5 in the effective treatment group, which were engaged in Kruppel-associated box (KRAB) domain-containing zinc-finger protein pathway and THOC5 pathway, respectively. Based on our current findings, we hypothesize that the anti-anemia effect of CCA on pregnant women with β-thalassemia might be related to translation regulation of spectrin synthesis, membrane stability, and eventually prolonged the life span of erythrocytes.

Correlation of Glycated Albumin and Glycated Hemoglobin with Glycemic Control in Patients with Diabetic Chronic Kidney Disease on Hemodialysis

Background and aims. Diabetes mellitus (DM) is the most common cause of end-stage renal disease (ESRD) worldwide and is the primary etiology of ESRD in Indonesia. It is estimated that there are 10 million patients with DM in Indonesia and about 25-40% of diabetics develop diabetic nephropathy (DN) within 25 years. Poor glycemic control is associated with increased mortality in a large observational study among diabetics on hemodialysis. Glycated hemoglobin, or known as HbA1c, was the currently recommended biomarker to monitor long-term glycemic control in diabetes mellitus guideline. However, it becomes underestimated in patients with DN on hemodialysis (DN-HD), because of 20- 50% reduction of erythrocyte lifespan, clinical use of iron therapy, and effects of recombinant human erythropoietin. Glycated albumin (GA), ketoamine formed via a non-enzymatic glycation reaction of serum albumin, is free from interference by erythrocyte lifespan or erythropoietin therapy and subsequently can be used as an alternative biomarker to monitor glycemic control in DN-HD. As albumin has a half-life of only 14-21 days* compared to Hb 60-100 days in well ESKD patients, thus GA may provide a better reflection of recent diabetic control than HbA1c. The aim of this study was to analyze the correlation between GA and HbA1c with glycemic control in DN-HD. Methods The study was an analytical observational study with a cross-sectional design. The subjects were consecutive patients with DN-HD who visited Hemodialysis Unit at Mohammad Hoesin General Hospital Palembang during August-November 2014. The glycemic control index was determined by the average value of 2 times a week pre-HD random blood glucose for 4 weeks (aRBG). Results. The subjects were 25 patients with an average age of 56.16±7.49 years old. The average value of GA was 26.94±7.74%. GA was strongly correlated with aRBG with r=0.776; p=0.000. After correcting for age, sex, and BMI, the correlations became significantly very strong (r=0.809, p <0.001). The simple linear regression for the relationship between GA and aRBG was aRBG=4,62×GA+42.74 (R2=0.602, P<0.001), estimating that a 1% increase of GA was associated with 4.62mg/dL increase of aRBG. After correcting for age, sex, & BMI, the correlations between HbA1c and aRBG were significant (r=0.852, p<0.001). Conclusion. GA was strongly correlated with glycemic control in patients with DN-HD and HbA1c was correlated better.

EFFECTS OF DIFFERENT DOSES OF GAMMA RAYS AND ASCORBIC ACID CONCENTRATION ON HUMAN RBCS FOR CONSERVATION PURPOSE

Background: Blood preservation and the development of sterile collection sets made possible the developments in blood components preparation, storage and transfusion that we have in today's blood banks and transfusion services. Objective: To investigate the effects of gamma irradiation, ascorbic acid and the combined effect of both on the lifespan of erythrocytes through determining red blood cells hemolysis for conserving it as long as possible without any change in erythrocytes biophysical properties. Methods: The blood was drawn from 10 healthy (5 males and 5 females) volunteers. Sample has been irradiated using 137Cs source. Different concentrations of ascorbic acid were used as an anti-oxidative agent for erythrocytes in blood suspension samples. A spectrometer was used for recording the data. Results: The results showed that 25% of RBCs hemolysis occurred after irradiation with 5Gy of gamma ray during 5th week of storage time while in un-irradiated sample 33.8% of RBCs hemolysis occurred during the 5th week. 25% of RBCs hemolysis for 10 μM of ascorbic acid concentration started after 7th week while for control started after 4th week. The minimum rates of RBCs hemolysis observed in the samples which pre-treated with (7 and 10) μM concentrations of ascorbic acid then irradiated with 1 Gy. Conclusion: The results indicated that irradiation of human blood with a certain doses of gamma ray, treated with small concentration of ascorbic acid or both, the two factors together can protect the blood from hemolysis for a longer time and the minimum rate of red blood cells hemolysis was observed for 10 μM ascorbic acid concentration then irradiation to 1 Gy of gamma ray. Keywords: Gamma ray, ascorbic acid, blood storage, red blood cells, oxidative damage Citation: Faraj KA, Abdullah SH, Muhammad SF. Effects of different doses of gamma rays and ascorbic acid concentration on human RBCs for conservation purpose. Iraqi JMS. 2019; 17(1): 50-56. doi: 10.22578/IJMS.17.1.8

Consequential of Hemoglobin E Disorder on Renal Complication of Diabetic Patients in Surin Hospital, Thailand

Background: Decreased erythrocyte life-span is associated with artificial low hemoglobinA1c (HbA1c) in hemoglobin E diabetes. This research aims to study the renal complication in hemoglobin E disorder diabetic patients in Surin hospital. Methods: This case control cohort study was conducted from 2009 to 2018.Patient’s clinical information, fasting plasma glucose (FPG), and HbA1c levels were collected and divided into two groups, homozygous group (HbEE) and negative dichlorophenol-indolephenolgroup (control group). Subjects were confirmed diabetics who already had been treated either with insulin, oral hypoglycemic drugs or a physician-prescribed diet. Target of diabetic control follow standard treatment, not try to intensive control. The endpoint was that of new diabetes nephropathy, defined as the development of macroalbuminuria (urine albumin &gt; 300 microgram/milligram) and rate of decline of estimated glomerular filtration rate (eGFR) per year. The hypothesis was that the cumulative average duration of disease was equal; the renal complication between two groups was not different. Results: From 2009 to 2018, 132 diabetic patients with hemoglobin E disorder and 493 diabetic patients with negative DCIP were included in the study. There were no significant differences in regard to age, duration of disease, systolic blood pressure (SBP), high-density lipoprotein (HDL) and low-density lipoprotein (LDL) among the groups. The hematocrit (Hct.), diastolic blood pressure (DBP), hemoglobin A1c (HbA1c), cholesterol (CHO), triglyceride (TG), serum creatinine (Cr) was significantly lower in HbEE group. The eGFR and FPG was significant high in HbEE group. When compared with controls, risk difference of macroalbuminuria was 4.2% lower prevalent in diabetic patients with hemoglobin E homozygous (P=0.008). The rate of decline in eGFR were significant much slower in HbEE group 0.64 ml/min/year and 0.71 ml/min/ year in control group (P&lt;0.001), after adjusted confounding factors. Conclusions: With long term cohort study, hemoglobin E disorder diabetic patients have less effect on renal complication when the mean fasting plasma glucose level was higher and lower HbA1c than negative DCIP group. Diabetic patients with hemoglobin E disorder should be monitored using HbA1c level as an indicator for long-term glycemic control.

Clinical Significance of Detecting the Erythrocyte Life Expectancy in Patients with Malignant Lymphoma Complicated with Anemia

To investigate the clinical value of erythrocyte life span in the diagnosis and treatment of lymphoma patients with anemia. The clinical data of 45 patients with lymphoma diagnosed by Department of Hematology in Beijing Union Hospital from January 2017 to June 2017 were collected. The life of erythrocytes was detected by alveolar gas CO test. The incidence of anemia in patients with malignant lymphoma was 46.7%, 40.0% of patients displayed the shorting of blood cell life and the hemolytic status existed in 15.56% of patients. The incidence of anemia was 47.1% in patients with DLBCL. Patients with B symptoms, bone marrow involvement, splenomegaly or LDH increase often accompanied with anemia, but only the splenomegaly and LDH level were significantly negatively correlated with red blood cell life; there was a significant difference in the effects of CHOP ± R regimen and other chemotherapy regimens (R+MINE/FC/SMILE/GDP) on patients with anemia and erythrocyte life span. The incidence of anemia in patients with lymphoma is high, red cell damage or shortened life may be involved in the mechanism of anemia, the use of a strong chemotherapy regimen can significantly shorten the red blood cell life of patients and aggravates anemia.

N-(2-Hydroxyethyl)-l-valyl-l-leucine in rat urine as a hydrolytic cleavage product of ethylene oxide adduct with globin

Ethylene oxide (EO), a genotoxic industrial chemical and sterilant, forms covalent adducts with DNA and also with nucleophilic amino acids in proteins. The adduct with N-terminal valine in globin [N-(2-hydroxyethyl)valine (HEV)] has been used in biomonitoring of cumulative exposures to EO. Here we studied in rats the fate of EO-adducted N-termini of globin after life termination of the erythrocytes. Rat erythrocytes were incubated with EO to produce the HEV levels in globin at 0.4-13.2µmol/g as determined after acidic hydrolysis. Alternative hydrolysis of the isolated globin with enzyme pronase afforded N-(2-hydroxyethyl)-L-valyl-L-leucine (HEVL) and N-(2-hydroxyethyl)-L-valyl-L-histidine (HEVH), the EO-adducted N-terminal dipeptides of rat globin α- and β-chains, respectively. The ratio of HEVL/HEVH (1:3) reflected higher reactivity of EO with the β-chain. The EO-modified erythrocytes were then given intravenously to the recipient rats. HEVL and HEVH were found to be the ultimate cleavage products excreted in the rat urine. Finally, rats were dosed intraperitoneally with EO, 50mg/kg. Herein, the initial level of globin-bound HEVL (11.7 ± 1.3nmol/g) decreased almost linearly over 60days corresponding to the life span of rat erythrocytes. Daily urinary excretion of HEVL was almost constant for 30-40days, decreasing faster in the subsequent phase of elimination. Recoveries of the total urinary HEVL from its globin-bound form were 84 ± 6% and 101 ± 17% after administrations of EO and the EO-modified erythrocytes, respectively. In conclusion, urinary HEVL appears to be a promising novel non-invasive biomarker of human exposures to EO.

Glycosylated Hemoglobin among Non-diabetic Patients Diagnosed as Benign Thyroid Lesions on Cytology: A Cross Sectional Study from a Tertiary Care Centre in India

Background: Hypothyroidism and diabetes usually coexist and are the most common endocrine disorders seen in India (1). Glycosylated Hb (HbA1c) is used for assessment of glycemia and American Diabetic Association (ADA) has recommended its use in diabetes and prediabetes (2). A value between 5.7% and 6.5% represents prediabetes while a value ≥6.5% is considered as diabetes mellitus (3). Glycosylated hemoglobin is a fraction of hemoglobin that undergoes non-enzymatic glycation over the circulatory life span of erythrocytes (4). Several studies have shown glycosylated Hb varies in different conditions like hemoglobinopathies, pregnancy and chronic kidney disease (5). Thyroid hormone plays an important role in glucose homeostasis (6). TSH regulates hematopoiesis in bone marrow (7). Hypothyroidism depresses the marrow which causes decreased erythrocyte production which alters the life span of erythrocytes. Altered life span causes spurious elevation of HbA1C (8, 9, 10). Hence, glycosylated Hb not only depends on glycemia but also on life span of RBC (11). Conditions which effect erythrocyte turnover or survival lead to falsely high or low Hb A1C levels (12). RBC turnover is increased in thyrotoxic states whereas hypothyroidism has the opposite effect (3). In the present study, we hypothesise that glycosylated hemoglobin shows variation in individuals with altered thyroid status. It also aim to establish if a correlation exits between fasting plasma glucose level and hemoglobin with glycosylated hemoglobin in patients with altered thyroid status. Aims and Objectives: To find a correlation between thyroid profile and glycosylated Hb in non-diabetic patients who have been diagnosed on cytology as benign thyroid lesions and Compare the fasting blood glucose and hemoglobin with glycosylated Hb in these patients. Material and Methods: A cross sectional study on 50 cases cytologically diagnosed as benign thyroid lesions in the Department of Pathology in ESIC Medical College and Hospital Faridabad were included in the study with consent of ethical committee. Data Analysis: Pearson’s coefficient was applied to test the association between variables. The significance level was set at 5%. Results: Out of 50 patients (n=25) 50% were hypothyroid, (n=13) 26% were hyperthyroid and (n=12) 24% were euthyroid and (n=22) 88% hypothyroid patients presented with HbA1C >6.5% and were labeled as Diabetic, (n=3) 12% hypothyroid patients were labelled as prediabetic and none was nondiabetic. Most of the euthyroid (n=11) 92% and all of the hyperthyroid patients (n=13) 100% had HbA1C in the nondiabetic range of 6.5%). The correlation of HbA1C with TSH, Hb and MCH of these patients showed statistical significance (p 6.5%) or prediabetic (HbAIc between 5.7 to 6.5%).