Efecto de la hemodiálisis de alto flujo en la dosis de eritropoyetina en pacientes con enfermedad renal crónica

Objetivo: Evaluar el requerimiento de eritropoyetina (EPO) tras el cambio de membrana de bajo a alto flujo en pacientes prevalentes en hemodiálisis. Secundariamente determinar la variación de β2-microglobulina, Proteína C reactiva (PCR) y ferritina. Material y métodos: Estudio retrospectivo observacional en pacientes prevalentes en hemodiálisis en dos centros de diálisis en Perú. Se determinaron las características clínicas y demográficas de los pacientes. Se determinó hemoglobina, porcentaje de saturación de transferrina, ferritina, Kt/V y dosis de EPO basal y cada 3 meses durante los 12 meses posteriores al cambio de dializador. Adicionalmente se determinó la PCR y β2-microglobulina a los 3, 6 y 12 meses. Resultados: Se incluyeron 58 pacientes que cumplieron con los criterios de inclusión y exclusión. La dosis de EPO basal fue 5 763,55 ± 3 000,69 UI/semana y a los 12 meses, 4031,18 ± 2 663,95 UI/semana (p=0,000) y la hemoglobina basal 11,10 ± 1,24 g/dl y a los 12 meses 11,69 ± 1,28 g/dl (p=0, 077). La β2-microglobulina disminuyó de 45,64 ± 11,39 mg/l a 26,26 ± 8,02 mg/l a los 12 meses (p=0,000). Conclusiones: En la población de estudio la dosis de EPO disminuyó 30% a los 12 meses sin cambios en la hemoglobina. La β2-microglobulina disminuyó 42,5% al año.

SUMMARY Objective: To evaluate the requirements of erythropoietin (EPO) after changing low membrane flow to high in patients on hemodialysis. Secondly, to evaluate changes in serum levels of beta 2 microglobulin, C-reactive protein (CRP) and ferritin. Methods: A retrospective-observational study was carried-out in patients on hemodialysis in two centers in Peru. Clinical and demographic characteristics of patients were reported. Levels of hemoglobin, ferritin saturation percentage, ferritin, Kt/V and EPO baseline doses and each three months for one year after changing the dialyzer were measured. Additionally, serum levels of C-reactive protein and beta 2 microglobulin at 3, 6 and 12 months were obtained. Results: A total of 58 were included; baseline EPO levels were 5 763.55 ± 3 000.69 UI/week and at 12 months were 4 031.18 ± 2663.95 UI/week (p=0.000); baseline hemoglobin was 11.10 ± 1.24 g/dl and 11.69 ± 1.28 g/dl (p=0.077) after 12 months. Serum levels of beta 2 microglobulin dropped from 45.64 ± 11.39 mg/l at baseline to 26.26 ± 8.02 mg/l at one year (p=0.000). Conclusions: EPO doses dropped 30% at 12 months with no changes in hemoglobin. Beta 2 microglobulin dropped 42.5% after one year.

Importance of assessing biomarkers and physiological parameters of anemia-induced tissue hypoxia in the perioperative period

Abstract Anemia is associated with increased risk of Acute Kidney Injury (AKI), stroke and mortality in perioperative patients. We sought to understand the mechanism(s) by assessing the integrative physiological responses to anemia (kidney, brain), the degrees of anemia-induced tissue hypoxia, and associated biomarkers and physiological parameters. Experimental measurements demonstrate a linear relationship between blood Oxygen Content (CaO2) and renal microvascular PO2 (y = 0.30x + 6.9, r2= 0.75), demonstrating that renal hypoxia is proportional to the degree of anemia. This defines the kidney as a potential oxygen sensor during anemia. Further evidence of renal oxygen sensing is demonstrated by proportional increase in serum Erythropoietin (EPO) during anemia (y = 93.806*10−0.02, r2= 0.82). This data implicates systemic EPO levels as a biomarker of anemia-induced renal tissue hypoxia. By contrast, cerebral Oxygen Delivery (DO2) is defended by a profound proportional increase in Cerebral Blood Flow (CBF), minimizing tissue hypoxia in the brain, until more severe levels of anemia occur. We hypothesize that the kidney experiences profound early anemia-induced tissue hypoxia which contributes to adaptive mechanisms to preserve cerebral perfusion. At severe levels of anemia, renal hypoxia intensifies, and cerebral hypoxia occurs, possibly contributing to the mechanism(s) of AKI and stroke when adaptive mechanisms to preserve organ perfusion are overwhelmed. Clinical methods to detect renal tissue hypoxia (an early warning signal) and cerebral hypoxia (a later consequence of severe anemia) may inform clinical practice and support the assessment of clinical biomarkers (i.e., EPO) and physiological parameters (i.e., urinary PO2) of anemia-induced tissue hypoxia. This information may direct targeted treatment strategies to prevent adverse outcomes associated with anemia.

Erythropoietin as a treatment option for indirect traumatic optic neuropathy: A pilot study

Purpose: Our study aims to evaluate the effectiveness of intravenous erythropoietin (EPO) in patients with indirect traumatic optic neuropathy (TON), assess the side effects, and compare the visual function results among three groups of patients who had received different treatment options – EPO, steroids, and observation. Methods: Patients with indirect TON presenting to the neuro?ophthalmology clinic from August 2019 to March 2020, were assigned to three groups, with six patients in each group. In group 1, patients were recruited prospectively and received recombinant human erythropoietin, whereas, in groups 2 and 3, patients were recruited retrospectively and received intravenous methylprednisolone followed by oral steroids and multivitamins, respectively. Groups 1 and 2 included patients presenting within 2 weeks of trauma, whereas group 3 included those presenting beyond that. Best?corrected visual acuity, pupillary reaction, color vision, and visual fields following treatment were measured. Results: Initial visual acuity in the EPO group ranged from 20/80 to no perception of light (No PL). The mean initial BCVA (1.82 logMAR, standard deviation [SD] = 0.847) improved to 1.32, SD = 0.93 logMAR after treatment recorded at the third month (P = 0.0375), with no significant adverse effects. The initial BCVA of group 2 ranged from 20/120 to No PL. The mean initial BCVA (1.95, SD = 0.77 logMAR) improved to 1.45 logMAR, SD = 0.97 after treatment (P = 0.0435) but three patients had side effects of steroids. Initial visual acuity in Group 3 ranged from 20/40 to no PL. The mean initial BCVA (1.09 logMAR, SD = 1.10) worsened to 1.19 logMAR, SD = 1.06 after treatment after treatment (P = 0.0193). The improvement in BCVA when compared between the three groups was not significant. Conclusion: Both erythropoietin and steroids are effective in the management of traumatic optic neuropathy. However, erythropoietin shows lesser or no side effects when compared to steroids

Pitiriasis liquenoide varioliforme aguda posterior al inicio de eritropoyetina / Acute varioliform lichenoid pityriasis following the initiation of erythropoietin

Resumen La pitiriasis liquenoide varioliforme aguda (PLEVA) pertenece a un grupo de enfermedades categorizadas como pitiriasis liquenoides, junto con la enfermedad febril úlcero-necrótica de Mucha-Habermann y la pitiriasis liquenoide crónica (PLC). Se caracteriza por la aparición aguda de múltiples pápulas eritemato-violáceas con posterior necrosis, discromía residual y cicatrices varioliformes. Dentro de las teorías patogénicas propuestas se encuentra el posible papel de agentes infecciosos, trastornos linfoproliferativos, complejos inmunes e incluso, asociación a medicamentos. Se presenta un casode una mujer adulta con un cuadro típico de PLEVA con confirmación histopatológica, cuyas lesiones aparecieron posteriormente al inicio de eritropoyetina.

Abstract Pityriasis lichenoides et varioliformes acuta (PLEVA) is part of a group of diseases clustered as pityriasis lichenoides, next to febrile ulceronecrotic Mucha-Habermann disease and pityriasis lichenoides chronica. It's characterized by a sudden onset of multiple erythematous and violaceous papules which develop necrosis, leaving residual dyschromia and varioliform scars. It's been hypothesized the possible role of infectious agents, lymphoproliferative diseases, immune complexes and drugs. We present the case of a woman with a typical PLEVA with histopathological confirmation, whose lesions appeared after therapy with erythropoietin.

Effects of recombinant human erythropoietin on cerebral blood flow in preterm infants: arterial spin labeling magnetic resonance imaging evaluation / 中国新生儿科杂志

Objective:To study the effects of recombinant human erythropoietin (rhEPO) on cerebral blood flow (CBF) in preterm infants using arterial spin labeling (ASL) magnetic resonance imaging (MRI).Methods:From September 2021 to June 2022, preterm infants (gestational age ≤32 weeks, birth weight ≤1 500 g) admitted to NICU of our hospital within 24 h after birth were randomly assigned into rhEPO group and control group for this prospective study. The rhEPO group was given rhEPO (500 IU/kg iv, once every other day for 2 weeks) within 72 h after birth plus symptomatic supportive treatment. The control group received same amount of normal saline injection. Both groups received brain MRI, diffusion-weighted imaging and ASL at adjusted gestational age of 35~37 weeks and CBF values of interested areas were measured.Results:A total of 85 infants were enrolled, including 40 in the rhEPO group and 45 in the control group. No significant differences existed in the incidences of periventricular-intraventricular hemorrhage, periventricular leukomalacia, focal white matter injury and extensive white matter injury between the two groups ( P>0.05). The CBF values [ml/(100 g·min)] of frontal cortex [left 15.1±3.9 vs. 17.9±3.1, right 15.9 (12.5, 17.8) vs. 18.1(16.1,20.2)], temporal cortex [left 15.8±4.3 vs. 18.6±3.8, right 16.3(13.2,19.4) vs. 18.1(15.7,19.7)], occipital cortex (left 15.8±6.1 vs. 18.8±3.3, right 16.8±5.5 vs. 19.3±4.8), basal ganglia (left 24.7±7.2 vs. 28.7±6.2, right 26.0±7.9 vs. 29.3±6.4) and thalamus (left 32.7±11.8 vs. 37.9±8.6, right 32.1±11.6 vs. 37.6±10.2) in the rhEPO group were significantly lower than the control group ( P<0.05). No significant differences existed of CBF value at the parietal cortex between the two groups ( P>0.05). Conclusions:Early application of rhEPO can reduce CBF in premature infants, which may be related to the neuro-protective effects of EPO.

Electrochemical biosensor for erythropoietin detection in athletes / Biossensor eletroquímico para detecção de eritropoietina em atletas / Biosensor electroquímico para detección de eritropoyetina en deportistas

ABSTRACT Introduction: The cytokine erythropoietin (EPO) is a crucial hormone for producing RBCs, which carry oxygenated blood to the rest of the body. Objective: This paper aimed to create an electrochemical detection based on Fe2O3-NiO nanoparticles and graphene oxide to measure EPO levels in athletes' blood. Methods: On a glassy carbon electrode, Fe2O3-NiO@GO was synthesized using the electrochemical deposition method. Results: The Fe2O3-NiO@GO/GCE was validated by structural characterizations using scanning electron microscopy (SEM). The Fe2O3-NiO@GO/GCE was found to be a suitable and stable erythropoietin biosensor with a linear range of 0-500 ng/l and a detection limit of 0.03ng/l in electrochemical tests using the DPV technique. Fe2O3-NiO@GO/erythropoietin was investigated as a biosensor for erythropoietin in athlete's plasma. Conclusion: The results showed that the values obtained for recovery (94.56% to 98.40) and RSD (2.01% to 3.22%) were acceptable, indicating that the suggested technique can be used as a practical erythropoietin biosensor in blood samples. Level of evidence II; Therapeutic studies - investigation of treatment outcomes.

RESUMO Introdução: A citocina eritropoietina (EPO), é referida como um hormônio crucial para a produção de hemácias, que transportam o sangue oxigenado para o resto dos corpos. Objetivos: O objetivo deste trabalho foi criar uma detecção eletroquímica baseada em nanopartículas de Fe2O3-NiO e óxido de grafeno para medir os níveis de EPO no sangue dos atletas. Métodos: Em um eletrodo de carbono vítreo, o Fe2O3-NiO@GO foi sintetizado usando o método de deposição eletroquímica. Resultados: O Fe2O3-NiO@GO/GCE foi validado por caracterizações estruturais utilizando microscopia eletrônica de varredura (SEM). O Fe2O3-NiO@GO/GCE foi considerado um biosensor eritropoietina adequado e estável com uma faixa linear de 0-500 ng/l e um limite de detecção de 0,03ng/l em testes eletroquímicos utilizando a técnica DPV. O Fe2O3-NiO@GO/extropoietina foi investigado como um biosensor de eritropoietina no plasma do atleta. Conclusão: Os resultados mostraram que os valores obtidos para recuperação (94,56% a 98,40) e RSD (2,01% a 3,22%) foram aceitáveis, indicando que a técnica sugerida pode ser usada como um prático biosensor de eritropoietina em amostras de sangue. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.

RESUMEN Introducción: La citoquina eritropoyetina (EPO), se conoce como una hormona crucial para la producción de glóbulos rojos, que transportan la sangre oxigenada al resto del cuerpo. Objetivos: El objetivo de este trabajo fue crear una detección electroquímica basada en nanopartículas de Fe2O3-NiO y óxido de grafeno para medir los niveles de EPO en la sangre de los deportistas. Métodos: Sobre un electrodo de carbono vítreo, se sintetizó Fe2O3-NiO@GO mediante el método de deposición electroquímica. Resultados: El Fe2O3-NiO@GO/GCE fue validado por caracterizaciones estructurales mediante microscopía electrónica de barrido (SEM). El Fe2O3-NiO@GO/GCE resultó ser un biosensor de eritropoyetina adecuado y estable con un rango lineal de 0-500 ng/l y un límite de detección de 0,03ng/l en ensayos electroquímicos mediante la técnica DPV. Se investigó el uso de Fe2O3-NiO@GO/extropoietina como biosensor de eritropoyetina en el plasma de atletas. Conclusión: Los resultados mostraron que los valores obtenidos para la recuperación (94,56% a 98,40) y la RSD (2,01% a 3,22%) fueron aceptables, lo que indica que la técnica sugerida puede ser utilizada como un biosensor práctico de eritropoyetina en muestras de sangre. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.

Prevalence and factors associated with the severity of anaemia among patients on chronic haemodialysis in Lagos, Nigeria

Anaemia is a global public health problem with high mortality and morbidity. It is also a common consequence of chronic kidney disease (CKD). There is a paucity of data on the actual burden of anaemia among patients on chronic haemodialysis (CHD) in Lagos, Nigeria. Objectives: To determine the prevalence and factors associated with the severity of anaemia among Nigerian patients undergoing chronic haemodialysis. Methods: This was a retrospective analysis of adult patients with end-stage renal disease (ESRD) on maintenance haemodialysis at the Lagos State University Teaching Hospital, Ikeja, Lagos. The data extracted from the clinical case files included the bio-demographic and clinical parameters, including the treatment modalities. Results: A total of 92 patients comprising 69 (75%) males and 23 (25.0%) females with the overall mean age of 48.2±14.0 years were included. Hypertension was the commonest aetiology of CKD and the average duration of haemodialysis was 16.6 months. The commonest access route for haemodialysis was a central line while 96.7% and 81.5% received erythropoietin and intravenous iron sucrose respectively. Seventy-three (79.3%) patients have had intra-dialysis blood transfusions in the past. Mild, moderate, and severe anaemia were recorded in 17%, 67%, and 16% respectively. The use of erythropoietin, iron sucrose, and increased frequency of blood transfusions correlated with the severity of anaemia. Conclusion: Anaemia is highly prevalent among patients with CKD on chronic haemodialysis. Increased frequency of blood transfusions, inadequate utilization of erythropoietin, and iron sucrose administration are associated with anaemia severity.

Risk of induction of corneal neovascularization with topical erythropoietin: an animal safety study

Purpose: To evaluate the pro-angiogenic effect of topical erythropoietin on cornea in chemical burn-injured rabbit eyes. Methods: The corneal alkali-burn injury was induced in 10 eyes of 10 rabbits using filter paper saturated with 1.0 mol sodium hydroxide. The eyes were categorized into the treatment group (n = 5) that received topical erythropoietin (3000 IU/mL) every 8 hr for one month versus the control group (n = 5) that received normal saline every 8 hr for one month. All eyes were treated with topical ciprofloxacin every 8 hr until corneal re-epithelialization was complete. Corneal epithelial defects, stromal opacity, and neovascularization were evaluated after the injury. At the conclusion of the study, the rabbits were euthanized and their corneas were submitted to histopathological examination. Results: Baseline characteristics including the rabbits' weight and the severity of corneal injury were comparable in two groups. Time to complete corneal re-epithelialization was 37 days in the treatment group and 45 days in the control group (P = 0.83). There was no significant difference between the groups in the rate of epithelial healing or corneal opacification. Clinical and microscopic corneal neovascularization was observed in one eye (20%) in the treatment group and two eyes (40%) in the control group (P = 0.49). Conclusion: Recombinant human erythropoietin administered topically did not induce vessel formation in rabbit corneas after chemical burn.

Regulation of osteogenic differentiation under hypoxia by EphrinB2/EphB4 in MC3T3-E1 cells / 口腔疾病防治

Objective @# To investigate the effect of erythropoietin producing hepatocyte kinase receptor ligand B2-erythropoietin producing hepatocyte kinase receptor B4 (EphrinB2/EphB4) on the osteogenic differentiation of MC3T3-E1 cells in a hypoxic environment to provide experimental evidence for hypoxia regulation of osteoblast differentiation.@*Methods @# Control groups and cobalt chloride (CoCl2)-induced hypoxia groups were set up first. qRT-PCR was used to detect the mRNA expression of the osteogenic markers alkaline phosphatase (ALP), collogen1 (COL I), runt-related transcription factor 2 (RUNX2) and osteocalcin (OCN). ALP staining was used to detect the activity of cell alkaline phosphatase after osteogenic induction. The mRNA and protein expression levels of hypoxia inducible factor-1α (HIF-1α), EphrinB2 and EphB4 in the two groups were detected via qRT-PCR and Western blot. Then, the CoCl2 + inhibitor group was established. NVP-BHG712, an EphB4 phosphorylation inhibitor, was added to this group to prevent EphrinB2 from binding to EphB4 and producing signals. qRT-PCR and Western blot were used to detect the mRNA and protein expression of osteogenic markers, including ALP, RUNX2, COL I, and OCN. ALP staining and Alizarin red S staining were used to measure osteoblast differentiation and mineralization. @*Results @# Compared with the control group, the mRNA expression of the osteogenic differentiation markers ALP, RUNX2, COL-1, and OCN in MC3T3-E1 cells increased, and ALP activity and mineralization were enhanced under CoCl2-induced hypoxia in vitro (P<0.05). Additionally, the expression of HIF-1α, EphrinB2 and EphB4 was upregulated at the mRNA and protein levels under hypoxia (P<0.05). When NVP-BHG712 was used to block the connection between EphrinB2 and EphB4, the expression of osteogenic markers and ALP activity and mineralization were decreased (P<0.05).@*Conclusion@#EphrinB2/EphB4 can promote osteogenic differentiation of MC3T3-E1 cells and increase the expression of osteogenic markers and tissue mineralization in a hypoxic environment.

A retrospective study and value analysis of erythropoietin in improving postoperative anemia in renal transplant patients / 现代泌尿外科杂志

【Objective】 To explore the effects of early application of erythropoietin (EPO) in patients with anemia after renal transplantation. 【Methods】 Patients who underwent renal transplantation in the First Affiliated Hospital of Soochow University were retrospectively analyzed. According to whether EPO was applied after operation, the patients were divided into EPO group and routine group. Patients with delayed renal function recovery were excluded, and the remaining patients were further analyzed. The general, laboratory and follow-up data of the two groups were compared, and adverse drug reactions were observed. 【Results】 The hemoglobin (P=0.026), red blood cell count (P=0.038) and hematocrit (P=0.011) in EPO group were higher than those in the routine group 2 weeks after operation, while the postoperative serum creatinine level was lower (P=0.001). Since the first week after operation, the reticulocyte count in EPO group was significantly higher than that in routine group (P<0.01). There was a negative correlation between hemoglobin and serum creatinine in EPO group at week 1 (r=-0.375, P=0.010) and week 2 (r=-0.386, P=0.008). During the treatment, 6 patients showed transient elevation of serum potassium, which returned to normal after symptomatic treatment, and no obvious adverse drug reactions were observed. 【Conclusion】 Continuous application of erythropoietin in the early stage after renal transplantation can significantly improve anemia in renal transplant patients and promote the recovery of renal function.

Kidney xenotransplantation: status quo and development trend of physiological research / 器官移植

Organ transplantation is the most effective treatment for all categories of end-stage organ diseases. To resolve the shortage of donors in organ transplantation, widespread attention has been diverted to xenotransplantation. At present, clinicians mainly highlight the problems related to xenotransplantation rejection and viral infection. The physiology of xenotransplantation has been rarely studied. Kidney performs endocrine function by producing erythropoietin (EPO), renin and activating vitamin D. Although these pathways are usually well preserved in allogeneic transplantation, species-specific differences, especially those between pigs and non-human primates, may still affect the physiological function of transplant organs. In this article, the changes of EPO, renin-angiotensin-aldosterone system (RAAS) and active vitamin D3 of pig and human after xenotransplantation were illustrated, aiming to provide reference for subclinical research of xenotransplantation.

Potential Impact of Anemia and Iron Deficiency in Chronic Obstructive Pulmonary Disease Patients and its Relation to Serum Levels of Erythropoietin

Background: Little is known about iron deficiency (ID) and anemia in chronic obstructive pulmonary disease (COPD). To study the prevalence and treatment of anemia in patients of COPD and to check the hemoglobin level in all patients with COPD and to assess the quality of life (QOL) by administering the questionnaire in anemic COPD patients and comparing it with nonanemic COPD patients. Methods: We examined the subjects and administered a questionnaire based on dyspnea score to assess the impact of anemia on quality of life in patients of COPD. A total of 250 COPD patients were enrolled in the study, in that 62 patients were anemic and 188 patients were nonanemic in COPD patients. Results: The proportion of patients of nonanemic was found to be higher as compared with anemia having modified medical research council (mMRC) grade I (35.71% vs 20.00%), grade II (40.48% vs 26.67%), and grade IV (11.90% vs 6.67%), while the proportion of patients of anemia was found to be higher than that of nonanemic having mMRC grade III (46.67% vs 11.90%). Difference in mMRC grade of patients of anemia and nonanemic was found to be statistically highly significant. Out of 250 patients of COPD, hemoglobin levels of 62 (26.32%) were found to be below normal levels and were diagnosed as anemic and classified as anemia in the present study, while hemoglobin levels of the rest 188 (73.68%) patients were found to be normal and were classified as nonanemic. Prevalence of anemia in COPD = 24.87%. Conclusion: Anemia occurs frequently in patients of COPD and is associated with poor quality of life and increased morbidity in the form of number of exacerbations and hospital admissions. Correcting anemia in these patients may improve their clinical outcomes

Effects of Recombinant Erythropoietin on Hemoglobin Levels and Blood Transfusion Needs in Patients with Preoperative Anemia Undergoing Cardiac Surgery

Introduction:Preoperative anemia is an important and relatively common problem in patients undergoing cardiac surgery, and its treatment is crucial in improving postoperative outcomes. The use of recombinant erythropoietin is one of the suggested methods in this field. Therefore, in the present study, we sought to evaluate the effects of recombinant erythropoietin on hemoglobin (Hb) levels and blood transfusion needs in cardiac surgery in patients with preoperative anemia. Methods: This randomized nonblind clinical trial was performed on patients with mild?to?moderate anemia (Hb <12 g/dL in men and Hb <11 g/dL in women) undergoing cardiac surgery at a referral heart hospital (Tehran, Iran). The patients were randomly divided into two groups of 33 patients. In the intervention group, recombinant erythropoietin was administered at a dose of 500 IU/kg one to three days before surgery. Intra? and postoperative Hb levels and the need for blood transfusion were recorded during surgery and for 3 days afterward. Results: The use of packed red blood cells in the operating room was similar in the intervention and control groups (P = 0.156), but it was significantly lower in the intensive care unit in the intervention group (P = 0.030). The mean Hb, which was initially identical in the two groups (P > 0.05), showed a significantly lower decrease in the intervention group (P = 0.001). No significant differences were observed concerning other variables. Conclusions: The use of recombinant erythropoietin (500 IU/kg/day) one to three days before cardiac surgery in our anemic patients blunted a reduction in Hb levels and decreased blood transfusion needs.

Effect of intranasal administration of NeuroEPO in the histological structure of the olfactory mucosa of Wistar rats / Efecto de la administración intranasal de NeuroEPO en la estructura histológica de la mucosa olfatoria de ratas Wistar

Introduction: Strokes and neurodegenerative diseases are major global health problems, not only because they cause high mortality and disability, but due to the lack of effective therapies. NeuroEPO, a variant of recombinant human erythropoietin (rHu-EPO) with a low sialic acid content, has shown encouraging results as a potential neuroprotective agent when administered intranasally. Objective: To determine the effect of intranasal administration of NeuroEPO on the histological structure of the olfactory mucosa of Wistar rats. Materials and Methods: An experimental, prospective, and longitudinal study was conducted on Wistar rats. Ten healthy animals were randomly distributed into two groups of five each. The control group received a vehicle (0.3 μl/g/day) and the treated group received NeuroEPO (300 μg/kg/day). Both treatments were administered intranasally for 28 days. The histological characteristics of the olfactory mucosa were evaluated. The medians between the study groups were compared using the Mann-Whitney U test. Results: There were no alterations in the histological characteristics of the olfactory epithelium. However, slight hypertrophy and hyperplasia of the Bowman's glands were observed at the level of the lamina propria in the group treated with NeuroEPO. Conclusions: The administration of the nasal formulation of NeuroEPO did not induce histological alterations of the olfactory mucosa of Wistar rats under the experimental conditions of this research.

Introducción: Los accidentes cerebrovasculares y las enfermedades neurodegenerativas constituyen un importante problema de salud mundial. No solo porque causan una alta mortalidad y discapacidad, sino por la falta de terapias eficaces para tratarlos. La NeuroEPO, una variante de la eritropoyetina humana recombinante (rHu-EPO) con bajo contenido en ácido siálico, ha mostrado resultados alentadores como potencial agente neuroprotector al ser administrada por vía intranasal. Objetivo: Determinar el efecto de la administración intranasal de NeuroEPO en la estructura histológica de la mucosa olfatoria de ratas Wistar. Materiales y Métodos: Se realizó un estudio experimental, prospectivo y de corte longitudinal en ratas Wistar. Se utilizaron diez animales sanos distribuidos aleatoriamente en dos grupos de cinco cada uno. El grupo control recibió vehículo (0,3 μl/g/día) y el grupo tratado recibió NeuroEPO (300 μg/kg/día). Ambos tratamientos fueron administrados por vía intranasal durante 28 días. Fueron evaluadas las características histológicas de la mucosa olfatoria. Las medianas de los grupos del estudio fueron comparadas mediante la prueba U de Mann-Whitney. Resultados: No se evidenciaron alteraciones en las características histológicas del epitelio olfatorio. Sin embargo, a nivel de la lámina propia en el grupo tratado con NeuroEPO, se observó una ligera hipertrofia e hiperplasia de las glándulas de Bowman. Conclusiones: La administración de la formulación nasal de NeuroEPO no indujo alteraciones histopatológicas de la mucosa olfatoria de ratas Wistar en las condiciones experimentales de esta investigación.

Pattern and Severity of Anaemia in Predialysis Chronic Kidney Disease Patients in Bangladesh: A Tertiary Care Hospital Study

Background: Anemia is a common complication in chronic kidney disease (CKD), and is associated with a reduced quality of life, and increased morbidity and mortality. The mechanisms involved in ananaemiassociated with CKD are diverse and complex. They include a decrease in endogenous erythropoietin (EPO) production, absolute and/or functional iron deficiency, and inflammation with increased hepcidin levels, among others. Objective: The objective of our study was to investigate the prevalence and severity of anaemia in pre-dialysis patients, and chronic kidney disease patients in Bangladesh.Material & Methods:This was a case-control prospective study conducted with over 300 Bangladeshi non-patients as the control group A and 87 with different stages of chronic kidney disease (CKD) patients as the case group B in the department of Nephrology BSMMU from April’2004 to June 2006. The normal people who had no history of diabetes mellitus, hypertension, or CKD and were not on any medication were controlled and different stages of the CKD patients who had no history of blood transfusion, erythropoietin and parental iron infusion were cases.Results:Out of 300 normal populations male was 158(52.7%) and the female was 142(47.3%) and the mean haemoglobin level of the male was 13.94 g/dl and the female was 12.29 g/dl. Among males 24(15.2%) and females 55(38.7%) were anaemic and the overall prevalence of anaemia was noted at 26.3%. Of the total anaemic people, 25% was microcytic anemia. Out of 87 CKD patients, 56 (64%) were male and 31 (36%) were female. The overall prevalence of anaemia in CKD patients was 95.4%. The haemoglobin level was <11g/dl in 57.14% patients with CCr 30-59 ml/min/1.73m2 which increases to 87.5 % in patients with CCr 15-29 ml/min/1.73m2, which also increases to 94.2 % in patients with CCr<15 ml/min/1.73m2. Mean haemoglobin was observed at 8.6 g/dl, 9.54 g/dl and 11.25 g/dl in stage V, stage IV and stage III CKD patients respectively. Anaemia appeared at 43.53 ml/min/1.73 m2 of CCR.Conclusions:The results demonstrate that patient with reduced renal function is more likely to have anaemia and the prevalence and severity of anaemia increase with declining kidney function. CCr and TSAT is the important predictor of anaemia. In a significant number of the CKD, patient anaemia was associated with iron deficiency.

Efecto hipoglicemiante de la NeuroEPO en ratas con y sin diabetes mellitus / Hypoglycemic effect of NeuroEPO in diabetic and non-diabetic rats

RESUMEN Introducción: La NeuroEPO es una variante no-hematopoyética de la eritropoyetina recombinante humana, que pudiera tener efecto hipoglicemiante. Objetivo: Evaluar la influencia de la NeuroEPO sobre la glicemia de ratas con diabetes mellitus y ratas no-diabéticas. Material y Métodos: Se realizaron experimentos en ratas Wistar con diabetes inducida por estreptozotocina, con y sin tratamiento con insulina, y en ratas no-diabéticas con una sobrecarga de glucosa. En cada experimento, un grupo recibió una inyección subcutánea de NeuroEPO (0,5 mg/kg) y otro el vehículo, y se determinó la glicemia durante 120 minutos. Se realizaron comparaciones mediante análisis de varianza de una y dos vías, seguidas por la prueba de Bonferroni. Las diferencias se consideraron significativas con valores de p < 0,05. Resultados: En las ratas diabéticas sin tratamiento con insulina, los niveles de glicemia del grupo con NeuroEPO disminuyeron de forma significativa. En las ratas no-diabéticas que recibieron NeuroEPO y una sobrecarga de glucosa, la glicemia fue similar al grupo control. En las ratas diabéticas que recibieron NeuroEPO e insulina la reducción de la glicemia fue mayor que en el grupo que solo recibió insulina. Conclusiones: La NeuroEPO tiene un efecto hipoglicemiante en ratas diabéticas, por un mecanismo insulinotrópico que muestra sinergismo con la insulina en el tratamiento de la hiperglicemia. Sin embargo, la NeuroEPO no influye en la tolerancia a la glucosa de ratas no-diabéticas, al menos de forma inmediata. Es necesario profundizar en los mecanismos mediante los cuales la NeuroEPO puede reducir la hiperglicemia, y la influencia de esta sustancia en condiciones de normoglicemia.

ABSTRACT Introduction: NeuroEPO is a non-hematopoietic variant of human recombinant erythropoietin, which may have a hypoglycemic effect. Objectives: To evaluate the influence of NeuroEPO on glycemia in diabetic and non-diabetic rats. Material and Methods: The experiments were conducted in Wistar rats with streptozotocin-induced diabetes with and without insulin treatment, and in non-diabetic rats with glucose overload. In each experiment, one group received a subcutaneous injection of NeuroEPO (0.5 mg/kg) and the other group received a vehicle. Glycemia was determined in 120 min. Comparisons were made using one-and two-way analysis of variance, followed by the Bonferroni test. The differences were considered significant with p values < 0,05. Results: In diabetic rats without insulin treatment, glycemic levels decreased significantly in the group that received NeuroEPO. In nondiabetic rats that received NeuroEPO and a glucose overload, glycemia was similar to that in the control group. In diabetic rats that received NeuroEPO and insulin, the glycemia reduction was greater than in the group that only received insulin. Conclusions: NeuroEPO has a hypoglycemic effect in diabetic rats due to an insulinotropic mechanism that shows synergism with insulin in the treatment of hyperglycemia. However, NeuroEPO does not influence the glucose tolerance in non-diabetic rats, at least immediately. It is necessary to delve into the mechanisms by which NeuroEPO can reduce hyperglycemia and the influence of this substance under conditions of normoglycemia.

Role of preoperative erythropoietin in the optimization of preoperative anemia among surgical patients — A systematic review and meta-analysis

Abstract Preoperative anemia is a common finding. Preoperative allogeneic transfusion, iron therapy, vitamin supplementation and erythropoietin therapy are the current management strategies for preoperative anemia. Previous reviews regarding erythropoietin were limited to specialties, provided little evidence regarding the benefits and risks of erythropoietin in managing preoperative anemia and included non-anemic patients. The purpose of our systematic review was to determine the role of erythropoietin solely in preoperatively anemic patients and to investigate the complications of this treatment modality to produce a guideline for preoperative management of anemic patients for all surgical specialties. The PubMed/Medline, Google Scholar, and Cochrane Library were searched for randomized trials evaluating the efficacy of erythropoietin in preoperative anemia. The risk ratio (RR) and standardized mean difference (SMD) was used to pool the estimates of categorical and continuous outcomes, respectively. Allogeneic transfusion and complications and the 90-day mortality were the primary outcomes, while the postoperative change in hemoglobin, bleeding in milliliters and the number of red blood cell (RBC) packs transfused were the secondary outcomes. Results: Eight studies were included, comprising 734 and 716 patients in the erythropoietin group and non-erythropoietin group, respectively. The pooled estimate by RR for allogeneic transfusion was 0.829 (p = 0.049), while complications and the 90-day mortality were among the 1,318 (p = 0.18) patients. Conclusion: Preoperative erythropoietin provides better outcomes, considering the optimization of preoperative anemia for elective surgical procedures. The benefits of erythropoietin are significantly higher, compared to the control group, while the risks remain equivocal in both groups. We recommend preoperative erythropoietin in anemic patients.

Analysis of serum erythropoietin test results of adult patients with Kaschin-Beck disease in Qinghai Province / 中华地方病学杂志

Objective:To analyze the results of serum erythropoietin (EPO) in adults patients with Kaschin-Beck disease (KBD) in Qinghai Province.Methods:According to the "Diagnosis of Kaschin-Beck Disease" (WS/T 207-2010), by using clinical examination and X-ray, adults over 20 years old in KBD areas of Xinghai County and Guide County, Hainan Tibetan Autonomous Prefecture, Qinghai Province, were divided into KBD case group ( n = 109) and internal control group ( n = 95) in July 2019. At the same time, healthy people were selected as external control group ( n = 90) in Xunhua County. Then 2 ml fasting cubital venous blood was collected from the target population to separate serum. The serum EPO level was determined by enzyme-linked immunosorbent assay (ELISA). Results:There was no significant difference in age and sex ratio among the 3 groups ( F = 0.73, P = 0.484; χ 2 = 1.03, P = 0.611). There was significant difference in serum EPO levels among the 3 groups [KBD case, internal and external control groups: (30.74 ± 26.23), (19.73 ± 11.53) and (10.83 ± 4.48) U/L, F = 26.51, P < 0.001]. Multiple comparisons showed that there were statistically significant differences in serum EPO levels between KBD case group and the internal and external control groups ( P < 0.05), but there was no significant difference between the internal and external control groups ( P > 0.05). Conclusions:The serum EPO level in adult KBD patients in Qinghai Province is increased significantly.

Eritrocitosis patológicas con niveles de eritropoyetina baja e incrementada: características clínicas y laboratoriales / Pathological erythrocytosis with low and increased erythropoietin levels: clinical and laboratory characteristics

RESUMEN: Introducción: Los pacientes con eritrocitosis patológicas en la altura, Eritrocitosis Secundaria o Eritrocitosis Patológica de Altura, ocasionalmente suelen presentar niveles de eritropoyetina (EPO) con variaciones notables respecto de los parámetros normales, reflejando ya sea concentraciones muy bajas o muy altas de EPO. Objetivo: Analizar la prevalencia de las eritrocitosis con EPO disminuida y de las eritrocitosis con EPO incrementada, así como, las características laboratoriales y clínicas inmiscuidas entre ellas. Material y Métodos: Se realizó un estudio descriptivo transversal de tipo retrospectivo. Se analizó historias clínicas de 44 pacientes eritrocíticos; de estos, 22 pacientes (5 mujeres, 17 varones) con registros de EPO sérica disminuida (100 mUI/ml) que constituyeron el Grupo 2. Todos ellos residentes a una altura >3650 m s. n. m. Se recolectó datos demográficos, clínicos y laboratoriales; asimismo, datos referentes a los tratamientos administrados, seguimiento y respectivas respuestas en ambos grupos. Resultados: La frecuencia de las eritrocitosis patológicas con EPO disminuida representó 5 % y de aquellas con EPO elevada 5 %.: Se debe considerar estudios específicos en pacientes eritrocíticos con EPO baja para descartar Policitemia Vera, asimismo, los pacientes con EPO incrementada implican mayor complejidad en el manejo médico.

ABSTRACT: Introduction: Patients with pathological erythrocytosis at high altitude, Secondary Erythrocytosis or High Altitude Pathological Erythrocytosis, occasionally present notable variations of erythropoietin (EPO) levels regarding normal parameters, reflecting either very low or very high EPO concentrations. Objective: To analyze the prevalence of erythrocytosis with decreased EPO and erythrocytosis with increased EPO, as well as the laboratory and clinical characteristics involved between them. Material and methods: A retrospective cross-sectional descriptive study was conducted. Clinical records of 44 patients with erythrocytosis were analyzed; of these, 22 (5 women, 17 men) with records of decreased serum EPO (100 mIU/ml) ml) specified as Group 2. All of them were high altitude dwellers (>3650 m a. s. l). Demographic, clinical and laboratory data were collected, including data about administered treatments, follow-up and responses in both groups. Results: Frequency of pathological erythrocytosis with decreased EPO was 5% and with elevated EPO 5%. There were no representative differences between both groups concerning the CBC variables. Patients with increased EPO showed more complications of erythrocytosis (27%) compared to those with decreased EPO (0%). Two types of treatment regimen were evidenced in each group: a) ATV+ASA, and b) ATV+ASA+HU. Erythrocytosis patients with decreased EPO receiving ATV+ASA had higher favorable responses 90% versus those with elevated EPO (80%). The ATV+ASA+HU regimen reflected better applicability in the increased EPO group. Conclusion: Specific studies should be considered in erythrocytosis patients with decreased EPO to rule out Polycythemia Vera, similarly, patients with increased EPO imply more complexity at medical management.

Effects of ganglioside GM1 and erythropoietin on spinal cord injury in mice: Functional and immunohistochemical assessments

ABSTRACT Objectives: To evaluate the functional and immunohistochemical effects of ganglioside GM1 and erythropoietin following experimental spinal cord injury. Methods: Thirty-two male BALB/c mice were subjected to experimental spinal cord injury using the NYU Impactor device and were randomly divided into the following groups: GM1 group, receiving standard ganglioside GM1 (30 mg/kg); erythropoietin group, receiving erythropoietin (1000 IU/kg); combination group, receiving both drugs; and control group, receiving saline (0.9%). Animals were evaluated according to the Basso Mouse Scale (BMS) and Hindlimb Mouse Function Score (MFS). After euthanasia, the immunohistochemistry of the medullary tissue of mice was analyzed. All animals received intraperitoneal treatment. Results: The GM1 group had higher BMS and MFS scores at the end of the experiment when compared to all other groups. The combination group had higher BMS and MFS scores than the erythropoietin and control groups. The erythropoietin group had higher BMS and MFS scores than the control group. Immunohistochemical tissue analysis showed a significant difference among groups. There was a significant increase in myelinated axons and in the myelinated axon length in the erythropoietin group when compared to the other intervention groups (p < 0.01). Conclusion: Erythropoietin and GM1 have therapeutic effects on axonal regeneration in mice subjected to experimental spinal cord injury, and administration of GM1 alone had the highest scores on the BMS and MFS scales.