Erythropoietic Activity Research Articles

Acquired ineffective erythropoiesis in pediatric ECMO patients: Higher than anticipated serum EPO levels and lower than anticipated reticulocytes counts were associated with mortality.

ECMO plays a crucial role in treating severe respiratory and cardiac failure in pediatric patients. However, its impact on the regulation of erythropoietin (EPO) and erythropoiesis remains poorly understood. Factors such as improved oxygenation, inflammation, and hemodilution associated with ECMO treatment may influence EPO production and erythropoiesis. This study aimed to examine the effects of ECMO on EPO regulation and erythropoiesis in pediatric patients. This retrospective study serially quantified EPO serum levels, measured markers of erythropoiesis, and tabulated clinical outcomes of pediatric ECMO patients. Descriptive statistics and Pearson correlation coefficients were used to identify associations between biomarkers and clinical care parameters. Preliminary findings suggest a disconnection between elevated EPO levels and reduced markers of erythropoiesis or iron metabolism, indicating ineffective erythropoiesis. Patients receiving more than 10mL/kg/day of RBC transfusions had higher reticulocyte counts. Non-survivors had sustained elevations of EPO serum levels but reduced erythropoietic activity. In ECMO-treated pediatric patients, ineffective erythropoiesis is a significant concern and may be associated with higher mortality rates. Understanding the mechanisms behind this pathology could better inform clinical approaches and optimize management strategies. Further research is imperative to uncover the factors resulting in ineffective erythropoiesis in these patients and to develop targeted interventions.

Serum iron and transferrin saturation variation are circadian regulated and linked to the harmonic circadian oscillations of erythropoiesis and hepatic Tfrc expression in mice.

Serum iron has long been thought to exhibit diurnal variation and is subsequently considered an unreliable biomarker of systemic iron status. Circadian regulation (endogenous ~24-h periodic oscillation of a biologic function) governs many critical physiologic processes. It is unknown whether serum iron levels are regulated by circadian machinery; likewise, the circadian nature of key players of iron homeostasis is unstudied. Here we show that serum iron, transferrin saturation (TSAT), hepatic transferrin receptor (TFR1) gene (Tfrc) expression, and erythropoietic activity exhibit circadian rhythms. Daily oscillations of serum iron, TSAT, hepatic Tfrc expression, and erythropoietic activity are maintained in mice housed in constant darkness, where oscillation reflects an endogenous circadian period. Oscillations of serum iron, TSAT, hepatic Tfrc, and erythropoietic activity were ablated when circadian machinery was disrupted in Bmal1 knockout mice. Interestingly, we find that circadian oscillations of erythropoietic activity and hepatic Tfrc expression are maintained in opposing phase, likely allowing for optimized usage and storage of serum iron whilst maintaining adequate serum levels and TSAT. This study provides the first confirmatory evidence that serum iron is circadian regulated, discerns circadian rhythms of TSAT, a widely used clinical marker of iron status, and uncovers liver-specific circadian regulation of TFR1, a major player in cellular iron uptake.

Nutritional Composition and Phytochemical Analysis of Ragi Microgreens

Ragi (elusine coracana) is one of the staple pseudocereal well known for his multitude of beneficial roles in promoting health and general wellbeing. Though it is one of the common millets and majorly consumed in south and north part of India, nutritional potential of ragi microgreens is yet to be explored. Considering other established microgreen’s nutritional significance, possible health implications, antioxidant properties and erythropoietic activity, present study was undertaken to estimate nutritional composition, qualitative phytochemical analysis, and quantification of bioactive ingredients of lyophilized ragi microgreens. Since lyophilisation is considered superior technique in preserving heat labile compounds, compared to other dehydration methods, it was used as the preferred sample for present study. Nutrient composition of ragi microgreens was found to be impressive with a protein content of 13.3 gm percent, crude fibre content 8 gm percent, iron mg percent vitamin C 112 mg percent and calcium are 91 gm percent. Preliminary phytochemical screening revealed presence of terpenoids, alkaloids, flavonoids, tannins, and sterols. Total chlorophyll estimation indicated that total chlorophyll content of lyophilized ragi microgreen is 623 mg/100 gm.

Serum Erythroferrone, a Biomarker of Erythropoietic Activity in End-Stage Renal Disease Patients

Serum Erythroferrone, a Biomarker of Erythropoietic Activity in End-Stage Renal Disease Patients

Anemia predictive indicator (API). how can we predict in three days the anemia that will develop in three months? case report

The Anemia Predictive Indicator (API) includes the analysis of the reticulocyte count, the reticulocyte hemoglobine content (HCr) and immature reticulocyte fraction (IRF). API reflects erythropoietic activity and allows immediate detection and correction of iron deficiency anemia, and the response can be observed on the second and third day after starting treatment. In this case report, a 79-year-old woman after a total knee replacement, API provided predictability at the onset of anemia, allowed the follow-up of anemia and its treatment, collaborated in clinical and medical decision, contributed to preventive actions and improve the patient's quality of life.

Effects of Hypoxia and Inflammation on Hepcidin Concentration in Non-Anaemic COVID-19 Patients.

Background/Objectives: This study aimed to explore the influence of hypoxia, inflammation, and erythropoiesis on hepcidin and other iron status parameters in non-anaemic COVID-19 patients admitted to the emergency unit before the introduction of therapeutic interventions. Methods: Ninety-six COVID-19 patients and 47 healthy subjects were recruited. Patients were subdivided into hypoxic or normoxic groups and, after follow-up, into mild and moderate, severe or critical disease severity groups. Iron, unsaturated iron-binding capacity (UIBC), ferritin, C-reactive protein (CRP), and interleukin 6 (IL-6) were measured on automatic analysers. ELISA kits were used for hepcidin and erythropoietin (EPO) determination. We calculated total iron-binding capacity (TIBC) and ratios of hepcidin with parameters of iron metabolism (ferritin/hepcidin, hepcidin/iron), inflammation (hepcidin/CRP, hepcidin/IL-6), and erythropoietic activity (hepcidin/EPO). Results: Hepcidin, ferritin, EPO, CRP, IL-6, ferritin/hepcidin, and hepcidin/iron were increased, while UIBC, TIBC, hepcidin/CRP, and hepcidin/IL-6 were decreased in hypoxic compared to normoxic patients as well as in patients with severe or critical disease compared to those with mild and moderate COVID-19. Regarding predictive parameters of critical COVID-19 occurrence, in multivariable logistic regression analysis, a combination of EPO and ferritin/hepcidin showed very good diagnostic performances and correctly classified 88% of cases, with an AUC of 0.838 (0.749-0.906). Conclusions: The hypoxic signal in our group of patients was not strong enough to overcome the stimulating effect of inflammation on hepcidin expression. EPO and ferritin/hepcidin might help to identify on-admission COVID-19 patients at risk of developing a critical form of the disease.

Iron Absorption: Molecular and Pathophysiological Aspects.

Iron is an essential nutrient for growth among all branches of life, but while iron is among the most common elements, bioavailable iron is a relatively scarce nutrient. Since iron is fundamental for several biological processes, iron deficiency can be deleterious. On the other hand, excess iron may lead to cell and tissue damage. Consequently, iron balance is strictly regulated. As iron excretion is not physiologically controlled, systemic iron homeostasis is maintained at the level of absorption, which is mainly influenced by the amount of iron stores and the level of erythropoietic activity, the major iron consumer. Here, we outline recent advances that increased our understanding of the molecular aspects of iron absorption. Moreover, we examine the impact of these recent insights on dietary strategies for maintaining iron balance.

Reticulocytes and Related Parameters in Clinical Practice

The development of hematologic analyzers allowed us to assess several additional parameters derived in addition to the number of reticulocytes. There is, among others, the calculation of immature reticulocyte fractions, reticulocyte maturity index, reticulocyte production index, and equivalent reticulocyte hemoglobin. The advantage of the equivalent hemoglobin and the content of hemoglobin is the insensitivity to interference by inflammation. These newly introduced parameters expand the possibilities to access bone marrow erythropoietic activity, iron stores, and the effectiveness of iron supplementation, vitamin B12, and folic acid supplementation. These parameters are also used to make decisions about blood transfusions or to detect occult internal bleeding.

NeuroEPO plus (NeuralCIM®) in mild-to-moderate Alzheimer’s clinical syndrome: the ATHENEA randomized clinical trial

BackgroundNeuroEPO plus is a recombinant human erythropoietin without erythropoietic activity and shorter plasma half-life due to its low sialic acid content. NeuroEPO plus prevents oxidative damage, neuroinflammation, apoptosis and cognitive deficit in an Alzheimer’s disease (AD) models. The aim of this study was to assess efficacy and safety of neuroEPO plus.MethodsThis was a double-blind, randomized, placebo-controlled, phase 2–3 trial involving participants ≥ 50 years of age with mild-to-moderate AD clinical syndrome. Participants were randomized in a 1:1:1 ratio to receive 0.5 or 1.0 mg of neuroEPO plus or placebo intranasally 3 times/week for 48 weeks. The primary outcome was change in the 11-item cognitive subscale of the AD Assessment Scale (ADAS-Cog11) score from baseline to 48 weeks (range, 0 to 70; higher scores indicate greater impairment). Secondary outcomes included CIBIC+, GDS, MoCA, NPI, Activities of Daily Living Scales, cerebral perfusion, and hippocampal volume.ResultsA total of 174 participants were enrolled and 170 were treated (57 in neuroEPO plus 0.5 mg, 56 in neuroEPO plus 1.0 mg and 57 in placebo group). Mean age, 74.0 years; 121 (71.2%) women and 85% completed the trial. The median change in ADAS-Cog11 score at 48 weeks was −3.0 (95% CI, −4.3 to −1.7) in the 0.5 mg neuroEPO plus group, −4.0 (95% CI, −5.9 to −2.1) in the 1.0 mg neuroEPO plus group and 4.0 (95% CI, 1.9 to 6.1) in the placebo group. The difference of neuroEPO plus 0.5 mg vs. placebo was 7.0 points (95% CI, 4.5–9.5) P = 0.000 and between the neuroEPO plus 1.0 mg vs. placebo was 8.0 points (95% CI, 5.2–10.8) P = 0.000. NeuroEPO plus treatment induced a statistically significant improvement in some of clinical secondary outcomes vs. placebo including CIBIC+, GDS, MoCA, NPI, and the brain perfusion.ConclusionsAmong participants with mild-moderate Alzheimer’s disease clinical syndrome, neuroEPO plus improved the cognitive evaluation at 48 weeks, with a very good safety profile. Larger trials are warranted to determine the efficacy and safety of neuroEPO plus in Alzheimer’s disease.Trial registrationhttps://rpcec.sld.cu Identifier: RPCEC00000232.

Regulation of haemoglobin concentration at high altitude.

Lowlanders sojourning for more than 1 day at high altitude (HA) experience a reduction in plasma volume (PV) that increases haemoglobin concentration and thus restores arterial oxygen content. If the sojourn extends over weeks, an expansion of total red cell volume (RCV) occurs and contributes to the haemoconcentration. While the reduction in PV was classically attributed to an increased diuretic fluid loss, recent studies support fluid redistribution, rather than loss, as the underlying mechanism. The fluid redistribution is presumably driven by a disappearance of proteins from the circulation and the resulting reduction in oncotic pressure exerted by the plasma, although the fate of the disappearing proteins remains unclear. The RCV expansion is the result of an accelerated erythropoietic activity secondary to enhanced renal erythropoietin release, but a contribution of other mechanisms cannot be excluded. After return from HA, intravascular volumes return to normal values and the normalisation of RCV might involve selective destruction of newly formed erythrocytes, although this explanation has been strongly challenged by recent studies. In contrast to acclimatised lowlanders, native highlanders originating from the Tibetan and the Ethiopian plateaus present with a normal or only mildly elevated haemoglobin concentration. Genetic adaptations blunting the erythropoietic response to HA exposure have been proposed as an explanation for the absence of more pronounced haemoconcentration in these populations, but new evidence also supports a contribution of a larger than expected PV. The functional significance of the relatively low haemoglobin concentration in Tibetan and Ethiopian highlanders is incompletely understood and warrants further investigation.

Serum Iron, Ferritin, Erythroferrone and their Inter-Correlation In Adult Cigarette Smokers: A Case-Control study

Cigarette smoking is one of the leading causes of lung and blood cancers worldwide. A higher risk of pulmonary injury is associated with elevated lung iron and ferritin levels. Erythroferrone (ERFE) is a newly discovered tumor necrosis factor (TNF) superfamily member produced by erythroblasts during erythropoiesis. Eventually, it suppresses hepcidin during enhanced erythropoietic activity. The current study investigated the relationship between serum ferritin, iron, and erythroferrone concentrations among adult smokers. This study included 76 selected adult cigarette smokers and 48 healthy individuals (non-smokers) as a control group. The enzyme-linked immunosorbent assay (ELISA) and chemiluminescent immunoassay (CLIA) biochemical techniques were used to accurately measure serum iron, ferritin, and erythroferrone. Cigarette smokers (CS) had a mean age of 42.75±2.92 years, while healthy control (HC) subjects had a mean age of 37.36±2.7 years. The findings have shown a significant increase in serum iron, ferritin, and EREF levels in CS (119± 4.30, 131.1±6.58, and 75.02±2.09) compared with HC (98.67±7.84, 85.50±4.12, and 65.74±2.25) respectively. This study has shown a significant positive correlation between serum EREF (P=0.0072, r=0.4089) and the duration of smoking <20 years and a moderate association between serum iron (P=0.1907, r=0.4511) and the duration of smoking <40 years. For the first time, this outcome shows increased serum EREF and overexpression by erythroblasts in subjects associated with smoking habits, along with increased serum iron and ferritin levels. An indicative correlation is found between EREF overexpression, iron overload, and hyperferritinemia with reference to the duration of smoking. The study also illustrates the interconnection between iron metabolism perturbations and ERFE overexpression induced by cigarette smoking.

The Effect of Ferritin Level on Respiratory Functions in Patients with β-Thalassemia Major

Introduction-Purpose β-thalassemia major (β-TM) is an autosomal recessive disorder caused by mutations in the β-globin gene of hemoglobin. The disease is characterized by splenomegaly due to ineffective erythropoiesis, iron accumulation signs in tissues as a result of increased iron absorption, bone expansion due to increased erythropoietic activity, and decreased tissue oxygenation. One of the effected organ can be the lungs due to excessive iron deposition in these patients. The current study aimed to investigate the effect of serum ferritin level, which is known as a marker of iron accumulation in tissues, on pulmonary function tests (PFT) in patients with β-TM. Methods and Materials Patients aged ≥6 years who were regularly followed in the pediatric hematology section of Mersin City Research and Training Hospital with a diagnosis of β-TM were included. All patients received regular blood transfusion and iron chelation therapy. Study participants underwent PFT prior to blood transfusion in the pediatric pulmonology section Results A total of 43 patients with β-TM were studied. Included patients were divided into two groups according to the mean annual ferritin level; low ferritin group if below 2000 ml/ng and high ferritin group if above 2000 ml/ng. The low ferritin group was consisted of 19 patients and the high ferritin group was consisted of 24 patients. The characteristics of these two groups are shown in Table 1. There were no statistical significance in age, gender, body mass index, age at diagnosis, mean annual hemoglobin, splenectomy, cardiac involvement and oxygen saturation among both groups, but the number of annual transfusion was significantly higher in the high ferritin group than lower ferritin group. When PFT parameters of both groups were compared, FVC (forced vital capacity) was statistically lower in the high ferritin group compared to the low ferritin group. Other parameters included FEV 1 (forced expiratory volume in 1 second), FEV 1/FVC ratio, PEF (peak expiratory flow) and FEF 25-75 (forced expiratory flow between 25% and 75% of vital capacity) were similar among groups. (Table 2) Discussion Patients with β-TM may accumulate iron in the interstitial area of the lungs which can lead fibrosis and impaired lung function over time. There are several studies investigated lung dysfunction and its etiology in these patients. Although the results of the studies are varied, the majority of them reported a restrictive pattern of respiratory dysfunction in thalassemia patients. Additionally, some studies showed the presence of mild or moderate obstruction in small airways and decrease in diffusion capacity with the increase of alveolar-capillary membrane thickness at advanced ages. In the present study, we found that patients with β-TM who had high ferritin level showed restrictive type lung function compared to those with low ferritin level. There were no difference among the groups in obstructive parameters (i.e. FEV 1, FEV 1/FVC, FEF 25-75) of PFT. In the literature, studies investigating PFT in patients with high ferritin levels had variable results, impaired or no change, in pulmonary status. In conclusion, loss of respiratory function and impaired tissue oxygenation in patients with β-TM may develop over time due to iron deposition in the interstitial area. PFT assessment of these patients is essential and recommended for the detection of early lung disease. Routine PFT follow in patients with β-TM of high ferritin values is highly important.

Placental ferroportin protein abundance is associated with neonatal erythropoietic activity and iron status in newborns at high risk for iron deficiency and anemia

BackgroundMurine data suggest that the placenta downregulates ferroportin (FPN) when iron is limited to prioritize iron for its own needs. Human data on the impact of maternal and neonatal iron status on placental FPN expression are conflicting. ObjectivesThis study aimed to identify determinants of placental FPN protein abundance and to assess the utility of the placental iron deficiency index (PIDI) as a measure of maternal/fetal iron status in newborns at high risk for anemia. MethodsPlacental FPN protein abundance was measured by western blots in placentae collected from 133 neonates born to adolescents (17.4 ± 1.1 y) carrying singletons (delivery gestational age [GA]: 39.9 ± 1.3 wk) and from 130 neonates born to 65 females (30.4 ± 5.2 y) carrying multiples (delivery GA: 35.0 ± 2.8 wk). Placental FPN and the PIDI (FPN:transferrin receptor 1) were evaluated in relation to neonatal and maternal iron-related markers (hemoglobin [Hb], serum ferritin [SF], soluble transferrin receptor [sTfR], total body iron [TBI], hepcidin, erythropoietin [EPO], erythroferrone). ResultsFPN protein was detected in all placentae delivered between 25 and 42 wk GA. Placental FPN protein abundance was associated with neonatal iron and erythropoietic markers (EPO: β: 0.10; 95% confidence interval [CI]: 0.06, 0.35; sTfR: β: 0.20; 95% CI: 0.03, 0.18; hepcidin: β: −0.06; 95% CI: −0.13, −0.0003; all P < 0.05). Maternal sTfR was only indirectly associated with placental FPN, with neonatal sTfR as the mediator (β-indirect: 0.06; 95% CI; 0.03, 0.11; P = 0.003). The PIDI was associated with neonatal Hb (β: −0.02; 95% CI: −0.03, −0.003), EPO (β: 0.07; 95% CI: 0.01, 0.14), and sTfR (β: 0.13; 95% CI: 0.004, 0.3) and with maternal SF (β: 0.08, 95% CI: 0.02, 0.14), TBI (β: 0.02; 95% CI: 0.009, 0.04), EPO (β: −0.10; 95% CI: −0.19, −0.01), sTfR (β: −0.16: 95% CI: −0.27, −0.06), and hepcidin (β: 0.05; 95% CI: 0.002, 0.11) at delivery (all P < 0.05). ConclusionsPlacental FPN abundance was positively associated with neonatal indicators of increased erythropoietic activity and poor iron status. The PIDI was associated with maternal and neonatal iron-related markers but in opposite directions. More data are needed from a lower-risk normative group of females to assess the generalizability of findings.These trials were registered at clinicaltrials.gov as NCT01019902 and NCT01582802.

Serum Erythroferrone in End Stage Renal Disease Patients: Relation to Iron Status, Anaemia and Erythropoiesis Stimulating Agents

Abstract Background Anaemia is a hallmark of chronic kidney disease (CKD), where erythropoietin deficiency and reduced iron availability by the negative iron regulator, hepcidin, are principal causes of the anaemia. Erythroferrone (ERFE), a hormone synthesized by erythroblasts, is a hepcidin inhibitor and increases iron absorption and mobilization, resulting in erythropoiesis stimulation. Thus, ERFE could be considered as one of potential clinical biomarkers for assessing erythropoiesis. Moreover, it has been found that ERFE is produced in response to erythropoietic stimulating agent (ESA) in CKD and thus could have a role in cure from anaemia in those patients. However, few studies focused on understanding the role of this hormone in the regulation of iron homeostasis. Aim of the Work To study the correlation between ERFE level and iron parameters and its response to iron/ESA in end stage renal disease (ESRD) patients with iron deficiency anaemia. Study design and methods A case-control study was carried out on 40 ESRD patients (GFR &amp;lt; 15 ml/min/1.73 mm3) with evidence of iron deficiency anaemia. Patients were further subdivided into 2 subgroups, where subgroup I included patients who received both iron and ESA (Erythropoietin) (n = 28) and subgroup II patients who were treated with iron only (n = 12). Ten age &amp; sex matched normal healthy subjects were included in the study as a control group. The studied parameters (ERFE, Hb, HCT%, MCV, MCH, serum iron, TSAT% and TIBC) were measured at baseline and then revaluated three months later after iron/ESA therapy. Erythroferrone was measured (baseline and post iron/ESA treatment) by ELISA. Results The present study was conducted on 40 ESRD patients with male to female ratio 1:1.5. Their mean age was 51.03±11.22 years and mean dry weight 73.4±13.08 Kg. The commonest risk factor was hypertension (32.5%). Treatment with iron ± EPO results in significant increase of Hb and serum iron in both patients' subgroups (p ˂ 0.001). Baseline and post treatment ERFE levels were higher in patients’ groups than in the control group with significant statistical difference (p = 0.016 &amp; 0.023 respectively). The highest level was in those patients treated with both iron and EPO (212.31±106.33 ng/L at baseline &amp; 520.00±255.26 post treatment). Positive correlation of ERFE level with both Hb and serum Iron (p-value &amp;lt;0.05) was detected. Conclusion Managing anaemia in ESRD patients remain a significant unmet challenge in those patients. Insight into iron homeostasis is important in order to develop new diagnostic as well as therapeutic modalities. Our study proved that ERFE is associated with iron/EPO therapy and positively correlated with hemoglobin and serum iron levels. Thus, ERFE could play a key role in the assessment of erythropoietic activity, as well as, in the treatment process among those patients in status of iron deficiency or iron overload.

Changes in Metabolomic Profiles Induced by Switching from an Erythropoiesis-Stimulating Agent to a Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitor in Hemodialysis Patients: A Pilot Study.

Hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) are a new class of medications for managing renal anemia in patients with chronic kidney disease (CKD). In addition to their erythropoietic activity, HIF-PHIs exhibit multifaceted effects on iron and glucose metabolism, mitochondrial metabolism, and angiogenesis through the regulation of a wide range of HIF-responsive gene expressions. However, the systemic biological effects of HIF-PHIs in CKD patients have not been fully explored. In this prospective, single-center study, we comprehensively investigated changes in plasma metabolomic profiles following the switch from an erythropoiesis-stimulating agent (ESA) to an HIF-PHI, daprodustat, in 10 maintenance hemodialysis patients. Plasma metabolites were measured before and three months after the switch from an ESA to an HIF-PHI. Among 106 individual markers detected in plasma, significant changes were found in four compounds (erythrulose, n-butyrylglycine, threonine, and leucine), and notable but non-significant changes were found in another five compounds (inositol, phosphoric acid, lyxose, arabinose, and hydroxylamine). Pathway analysis indicated decreased levels of plasma metabolites, particularly those involved in phosphatidylinositol signaling, ascorbate and aldarate metabolism, and inositol phosphate metabolism. Our results provide detailed insights into the systemic biological effects of HIF-PHIs in hemodialysis patients and are expected to contribute to an evaluation of the potential side effects that may result from long-term use of this class of drugs.

Isolation and evaluation of erythroid progenitors in the livers of larval, froglet, and adult Xenopus tropicalis.

Xenopus liver maintains erythropoietic activity from the larval to the adult stage. During metamorphosis, thyroid hormone mediates apoptosis of larval-type erythroid progenitors and proliferation of adult-type erythroid progenitors, and a globin switch occurs during this time. In addition, the whole-body mass and the liver also change; however, whether there is a change in the absolute number of erythroid progenitors is unclear. To isolate and evaluate erythroid progenitors in the Xenopus liver, we developed monoclonal ER9 antibodies against the erythropoietin receptor (EPOR) of Xenopus. ER9 recognized erythrocytes, but not white blood cells or thrombocytes. The specificity of ER9 for EPOR manifested as its inhibitory effect on the proliferation of a Xenopus EPOR-expressing cell line. Furthermore, ER9 recognition was consistent with epor gene expression. ER9 staining with Acridine orange (AO) allowed erythrocyte fractionation through fluorescence-activated cell sorting. The ER9+ and AO-red (AOr)high fractions were highly enriched in erythroid progenitors and primarily localized to the liver. The method developed using ER9 and AO was also applied to larvae and froglets with different progenitor populations from adult frogs. The liver to body weight and the number of ER9+ AOrhigh cells per unit body weight were significantly higher in adults than in larvae and froglets, and the number of ER9+ AOrhigh cells per unit liver weight was the highest in froglets. Collectively, our results show increased erythropoiesis in the froglet liver and demonstrate growth-dependent changes in erythropoiesis patterns in specific organs of Xenopus.

Reference intervals for reticulocyte indices, immature reticulocyte fraction, and the percentage of hypochromic red blood cells in adult large breed dogs using the ADVIA 2120 hematology analyzer.

Reticulocyte indices are used to characterize anemia, including the identification of regeneration. In people, the immature reticulocyte fraction (IRF), percentage of hypochromic red blood cells (%HYPO-RBC), and other reticulocyte indices have been used as earlier indicators of erythropoiesis and as valuable monitoring tools in the assessment of various therapies. The reference intervals (RI) of the IRF and %HYPO-RBC have not been reported in dogs. The objective of this study was to establish RIs for novel variables (IRF, %HYPO-RBC, and CH-delta) and assess RIs for more commonly reported reticulocyte indices in healthy dogs. RIs were calculated from blood results retrospectively collected from 106 client-owned healthy dogs at the time of induction into a blood donor program using the ADVIA 2120 hematology analyzer (Siemens Healthcare Diagnostics). For the calculation of RIs, appropriate tests were applied for outlier detection and normality assessment. For variables normally distributed, RIs and their respective 90% confidence intervals (CIs) were calculated using parametric methods, while for variables not normally distributed, robust methods were used and bootstrapping for calculating the 90% CIs. The following RIs were established: reticulocyte hemoglobin content (CHr) 24.5-28 pg, mean reticulocyte volume (MCVr) 85.9-99.3 fL, mean corpuscular hemoglobin concentration of reticulocytes (CHCMr) 271.0-306.3 g/L, IRF 10.4%-43.5%, CH-delta 0.5-4.3 pg, and percentage of hypochromic red blood cells (%HYPO-RBC) 0.10%-0.80%. The results of this study provide RIs for novel reticulocyte variables. Further studies are required to determine the clinical utility of IRF, %HYPO-RBC, and CH delta as early indicators of erythropoietic activity in canine patients.

Carbamoylated Erythropoietin-Induced Cerebral Blood Perfusion and Vascular Gene Regulation.

Cerebral hypoperfusion is associated with enhanced cognitive decline and increased risk of neuropsychiatric disorders. Erythropoietin (EPO) is a neurotrophic factor known to improve cognitive function in preclinical and clinical studies of neurodegenerative and psychiatric disorders. However, the clinical application of EPO is limited due to its erythropoietic activity that can adversely elevate hematocrit in non-anemic populations. Carbamoylated erythropoietin (CEPO), a chemically engineered non-erythropoietic derivative of EPO, does not alter hematocrit and maintains neurotrophic and behavioral effects comparable to EPO. Our study aimed to investigate the role of CEPO in cerebral hemodynamics. Magnetic resonance imaging (MRI) analysis indicated increased blood perfusion in the hippocampal and striatal region without altering tight junction integrity. In vitro and in vivo analyses indicated that hippocampal neurotransmission was unaltered and increased cerebral perfusion was likely due to EDRF, CGRP, and NOS-mediated vasodilation. In vitro analysis using human umbilical vein endothelial cells (HUVEC) and hippocampal vascular gene expression analysis showed CEPO to be a non-angiogenic agent which regulates the MEOX2 gene expression. The results from our study demonstrate a novel role of CEPO in modulating cerebral vasodilation and blood perfusion.

Eritropoez için Yeni Bir Parametre: Kordon Kanında Immatür Retikülosit Fraksiyon Değerlerinin Klinik Faktörlerle İlişkisi ve Yenidoğan için Referans Değerleri

Aim: The immature reticulocyte fraction (IRF) is a new parameter for the reticulocyte maturity index, representing an independent parameter of erythropoiesis that may be useful to better assess erythropoietic activity in neonates. In this study, the relationship between IRF values and clinical features in newborns was investigated and reference values were obtained. Material and Methods: Newborns between 28-40 weeks of gestation were included in this prospective study. At birth, maternal venous and cord blood samples were obtained for measurements of complete blood count (CBC), blood gases, and plasma concentrations of various biochemical parameters. Results: A total of 123 newborns, 99 term and 24 preterm, were included in the study. When the laboratory characteristics of the premature and term babies were compared according to their gestational weeks, while the median IRF value of cord blood was higher in term babies than in premature babies (p=0.039), other laboratory findings did not differ significantly. The median IRF value was 0.52 (range, 0.15-1.00) in term infants and 0.34 (range, 0.16-0.76) in preterm infants. IRF reference values for the term and preterm newborns were determined in cord blood. Moderately positive correlations were observed between the IRF levels and both the RDW (r=0.423, p&amp;lt;0.001) and the CRP (r=0.389, p&amp;lt;0.001) levels. Conclusion: The results of this study showed that newborns' IRF values were not affected by maternal variables and changed with the week of birth. The results of this study might be considered a guide for future studies using IRF value in newborns.

Normal range and predictors of serum erythroferrone in infants.

Erythroferrone (ERFE) has been identified as a hepcidin-regulating hormone synthetized by erythroblasts correlating to the erythropoietic activity and the needs for iron substrate in bone marrow of adults. The present study aimed to assess the ERFE serum concentrations and its predictors in infants. ERFE was explored at 4 time points during the first year of life in 45 healthy, breastfed, normal birth weight (NBW) infants, and 136 marginally low birth weight infants (LBW, 2000-2500 g) receiving iron (N = 58) or placebo (N = 78) between 6 weeks and 6 months of age. ERFE concentrations were low at birth, increasing gradually during the first year of life. In NBW infants, reference ranges (5th to 95th percentile) were at 6 weeks <0.005-0.99 ng/mL and at 12 months <0.005-33.7 ng/mL. ERFE was higher in LBW infants at 6 weeks but lower at 12 months compared to NBW and minimally affected by iron supplementation among LBW infants. Correlations of ERFE with erythropoietic and iron status markers were weak and inconsistent. The role of ERFE in the crosstalk of erythropoiesis and iron homeostasis remains unclear in infants and further studies on ERFE in infants and older children are warranted within the framework of the erythropoietin-ERFE-hepcidin axis. Normal range of erythroferrone in healthy infants is described for the first time. Erythroferrone in infants lacks correlation to iron status and markers of erythropoiesis. The findings indicate differences in infant regulation of iron homeostasis as compared to adults. The findings point to a need to study infant erythropoiesis separately from its adult counterpart. The findings may have clinical impact on management strategies of iron-loading anemia in infancy.