RESUMEN
OBJECTIVE: Our study aimed to investigate the relationship between vascular endothelial growth factor (VEGF), NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammatory complex, erythropoietin (EPO) levels, and ocular hemodynamics in patients diagnosed with primary open-angle glaucoma (POAG). METHODS: This is a prospective observational study. Patients diagnosed with POAG at The Sixth Hospital of Wuhan hospital between November 2022 and February 2023were enrolled.The patients were categorized into three groups based on the average visual field defect (mean deviation, MD) value: severe injury group (MD > 12 dB, 93 cases), moderate injury group (7 ≤ MD ≤ 12 dB, 89 cases), and mild injury group (MD < 7 dB, 85 cases). The levels of VEGF, NLRP3 inflammatory complex, EPO, and ocular hemodynamics were compared among the groups. Furthermore, the relationship between VEGF, NLRP3, EPO levels, and ocular hemodynamics in patients with POAG was analyzed using Pearson correlation analysis. After adjusting for confounding factors such as age and gender, multivariate Logistic regression analysis was performed with the ocular hemodynamics indexes being used as dependent variables, and VEGF, NLRP3, ASC, Caspase-1, and EPO being used as independent variables. RESULTS: A total of267 patients with POAG were enrolled. There were no significant differences in sex, age, body mass index, systolic blood pressure, diastolic blood pressure, smoking, alcohol consumption, and blood glucose between the two groups (P > 0.05). The levels of NLRP3, ASC, Caspase-1, and EPO in the severe and moderate injury groups were higher than those in the mild injury group, whereas the VEGF levels were lower in the severe and moderate groups compared to the mild group, showing significant differences (P < 0.05). The severe group exhibited higher levels of NLRP3, ASC, Caspase-1, and EPO than the moderate group, while the VEGF levels were lower in the severe group compared to the moderate group, showing significant differences (P < 0.05). The peak systolic velocity(PSV) and resistance index (RI) were higher in the severe and moderate groups than in the mild group, whereas the EDV was significantly lower in the severe and moderate groups compared to the mild group (P < 0.05). The severe group exhibited higher PSV and RI values compared to the moderate group, while the EDV was lower in the severe group compared to the moderate group, showing significant differences (P < 0.05). Pearson correlation analysis was performed to examine the relationship between VEGF, NLRP3, EPO levels, and ocular hemodynamics in patients with POAG. VEGF, NLRP3, ASC, Caspase-1, and EPO showed positive correlations with PSV and RI, and negative correlations with EDV in patients with POAG. Regression analysis showed that VEGF, NLRP3, ASC, Caspase-1 and EPO were significantly correlated with ocular hemodynamics in POAG (all P < 0.001). CONCLUSION: We demonstrated that the levels of VEGF, NLRP3 inflammatory complex, and EPO were highly associated with ocular hemodynamics in patients diagnosed with POAG.
Asunto(s)
Eritropoyetina , Glaucoma de Ángulo Abierto , Hemodinámica , Presión Intraocular , Proteína con Dominio Pirina 3 de la Familia NLR , Factor A de Crecimiento Endotelial Vascular , Humanos , Masculino , Femenino , Eritropoyetina/sangre , Eritropoyetina/metabolismo , Glaucoma de Ángulo Abierto/fisiopatología , Glaucoma de Ángulo Abierto/sangre , Glaucoma de Ángulo Abierto/metabolismo , Factor A de Crecimiento Endotelial Vascular/sangre , Persona de Mediana Edad , Estudios Prospectivos , Hemodinámica/fisiología , Presión Intraocular/fisiología , Anciano , Campos Visuales/fisiología , Biomarcadores/sangreRESUMEN
The objective of this study was to examine the effect of consuming ketone monoester plus a high dose of carbohydrate from glucose (KE + CHO) on the change in erythropoietin (EPO) concentrations during load carriage exercise compared with carbohydrate (CHO) alone. Using a randomized, crossover design, 12 males consumed KE + CHO (573 mg KE/kg body mass, 110 g glucose) or CHO (110 g glucose) 30 min before 4 miles of self-paced treadmill exercise (KE + CHO:51 ± 13%, CHO: 52 ± 12% VÌO2peak) wearing a weighted vest (30% body mass; 25 ± 3 kg). Blood samples for analysis were obtained under resting fasted conditions before (Baseline) consuming the KE + CHO or CHO supplement and immediately after exercise (Post). ßHB increased (p < 0.05) from Baseline to Post in KE + CHO, with no change in CHO. Glucose and glycerol increased (p < 0.05) from Baseline to Post in CHO, with no effect of time in KE + CHO. Insulin and lactate increased (p < 0.05) from Baseline to Post independent of treatment. EPO increased (p < 0.05) from Baseline to Post in KE + CHO and CHO with no difference between treatments. Although KE + CHO altered ßHB, glucose, and glycerol concentrations, results from this study suggest that KE + CHO supplementation before load carriage exercise does not enhance immediate post-exercise increases in EPO compared with CHO alone.
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Suplementos Dietéticos , Eritropoyetina , Ejercicio Físico , Glucosa , Humanos , Masculino , Eritropoyetina/administración & dosificación , Eritropoyetina/sangre , Ejercicio Físico/fisiología , Adulto , Glucosa/metabolismo , Glucosa/administración & dosificación , Glucemia/metabolismo , Estudios Cruzados , Cetonas/sangre , Cetonas/administración & dosificación , Adulto Joven , Carbohidratos de la Dieta/administración & dosificación , Ácido Láctico/sangre , Insulina/sangreRESUMEN
Exercise-induced inflammation can influence iron metabolism. Conversely, the effects of vitamin D3, which possesses anti-inflammatory properties, on ultramarathon-induced heart damage and changes in iron metabolism have not been investigated. Thirty-five healthy long-distance semi-amateur runners were divided into two groups: one group received 150,000 IU of vitamin D3 24 h prior to a race (n = 16), while the other group received a placebo (n = 19). Serum iron, hepcidin (HPC), ferritin (FER), erythroferrone (ERFE), erythropoietin (EPO), neopterin (NPT), and cardiac troponin T (cTnT) levels were assessed. A considerable effect of ultramarathon running on all examined biochemical markers was observed, with a significant rise in serum levels of ERFE, EPO, HPC, NPT, and cTnT detected immediately post-race, irrespective of the group factor. Vitamin D3 supplementation showed a notable interaction with the UM, specifically in EPO and cTnT, with no other additional changes in the other analysed markers. In addition to the correlation between baseline FER and post-run ERFE, HPC was modified by vitamin D. The ultramarathon significantly influenced the EPO/ERFE/HPC axis; however, a single substantial dose of vitamin D3 had an effect only on EPO, which was associated with the lower heart damage marker cTnT after the run.
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Biomarcadores , Colecalciferol , Suplementos Dietéticos , Hierro , Carrera de Maratón , Humanos , Colecalciferol/administración & dosificación , Método Doble Ciego , Masculino , Hierro/sangre , Hierro/administración & dosificación , Adulto , Femenino , Biomarcadores/sangre , Persona de Mediana Edad , Carrera/fisiología , Hepcidinas/sangre , Troponina T/sangre , Cardiopatías/prevención & control , Cardiopatías/etiología , Eritropoyetina/sangre , Eritropoyetina/administración & dosificaciónRESUMEN
The most popular treatment for end-stage renal illness is hemodialysis (HD). The study aimed to assess serum ferritin levels and their connection to Epoetin alfa resistance, along with exploring the link between hepatitis C virus, iron overload, and the prevalence of hepatitis C and B infections in chronic HD patients. This was a descriptive-analytical study conducted on 50 Patients with chronic kidney disease (CKD) who were on regular HD in the dialysis unit of Ibin Sina Teaching Hospital in Mosul City, Iraq. Out of 50 patients, 26 (52%) tested positive for Hepatitis C Virus (HCV) Antibody, 10 (20%) for Hepatitis B surface Antigen (HBsAg), and 14 (28%) tested negative for both. Higher serum iron and ferritin levels were found in HCV antibody-positive patients (p < 0.05). Despite Epoetin alfa treatment, patients with elevated ferritin levels exhibited lower Hemoglobin (HB) and Packed Cell Volume (p < 0.05). Non-diabetics exhibited significantly higher serum ferritin, Hemoglobin, Blood urea, and serum creatinine than diabetics (p < 0.05). A noteworthy association was seen between the quantity of blood transfusions and elevated levels of serum ferritin and total serum iron (p < 0.05). Most HD patients were anemic, with Hepatitis B and C prevalent. The main CKD causes were diabetes and hypertension. HCV-positive patients often showed mild to moderate iron overload, and high serum ferritin was linked to poor Epoetin alfa response. Dialysis can elevate blood urea, ferritin, and creatinine, worsening anemia. High ferritin levels may hinder response to Epoetin alfa and iron replacement. Excessive blood transfusions can lead to iron overload and inhibit erythropoiesis. Maintaining HB at 110-120 g/l improves quality of life and reduces anemia-related risks.
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Ferritinas , Hepatitis B , Hepatitis C , Diálisis Renal , Humanos , Diálisis Renal/efectos adversos , Ferritinas/sangre , Masculino , Femenino , Persona de Mediana Edad , Hepatitis C/sangre , Hepatitis C/complicaciones , Hepatitis B/sangre , Hepatitis B/complicaciones , Hepatitis B/epidemiología , Adulto , Hierro/sangre , Hemoglobinas/metabolismo , Hemoglobinas/análisis , Epoetina alfa/uso terapéutico , Hepacivirus , Anciano , Antígenos de Superficie de la Hepatitis B/sangre , Insuficiencia Renal Crónica/sangre , Insuficiencia Renal Crónica/terapia , Insuficiencia Renal Crónica/complicaciones , Eritropoyetina/sangre , Eritropoyetina/uso terapéuticoRESUMEN
Erythropoietin (EPO) has neuroprotective effects by increasing oxidative stress resistance and stabilizing redox balance. Ischemic-modified albumin (IMA) is a product of protein oxidation, and recent evidence suggests that IMA can be used as an indicator of oxidative damage. This study aimed to investigate serum EPO and IMA levels in obsessive-compulsive disorder (OCD) patients and to investigate the relationship between EPO and IMA levels and clinical variables such as disease duration and disease severity. A total of 68 adolescents (11-18 years old), including 35 OCD patients (18 males/17 females) and 33 healthy controls (14 males/19 females) without comorbid disorders matched for age, gender, and BMI, were included in the study. The enzyme-amplified chemiluminescence technique determined serum EPO levels, and serum IMA levels were determined by the spectrophotometric method. Serum EPO levels were lower in OCD patients compared to healthy controls (p = 0.002; Z = - 3.123), and serum IMA levels (ABSU) were significantly higher in the OCD group (p = 0.005). A significant positive correlation was found between IMA levels and the duration of OCD symptoms (p = 0.015, r = 0.409). The study's findings contribute to the growing body of evidence implicating inflammatory and oxidative processes in the pathogenesis of OCD. The potential of EPO and IMA levels as diagnostic biomarkers for OCD aligns with the ongoing efforts to identify reliable biological markers for the disorder. The positive correlation of IMA levels with the duration of OCD shows the importance of early detection of oxidative damage.
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Biomarcadores , Eritropoyetina , Trastorno Obsesivo Compulsivo , Albúmina Sérica Humana , Humanos , Masculino , Femenino , Adolescente , Eritropoyetina/sangre , Trastorno Obsesivo Compulsivo/sangre , Niño , Biomarcadores/sangre , Estudios de Casos y ControlesRESUMEN
BACKGROUND: The interaction between iron status and malaria is incompletely understood. We evaluated longitudinal changes in iron homeostasis in volunteers enrolled in malaria volunteer infection studies (VIS) and in Malaysian patients with falciparum and vivax malaria. METHODS: We retrieved data and samples from 55 participants (19 female) enrolled in malaria VIS, and 171 patients (45 female) with malaria and 30 healthy controls (13 female) enrolled in clinical studies in Malaysia. Ferritin, hepcidin, erythropoietin, and soluble transferrin receptor (sTfR) were measured by ELISA. FINDINGS: In the VIS, participants' parasitaemia was correlated with baseline mean corpuscular volume (MCV), but not iron status (ferritin, hepcidin or sTfR). Ferritin, hepcidin and sTfR all increased during the VIS. Ferritin and hepcidin normalised by day 28, while sTfR remained elevated. In VIS participants, baseline ferritin was associated with post-treatment increases in liver transaminase levels. In Malaysian patients with malaria, hepcidin and ferritin were elevated on admission compared to healthy controls, while sTfR increased following admission. By day 28, hepcidin had normalised; however, ferritin and sTfR both remained elevated. INTERPRETATION: Our findings demonstrate that parasitaemia is associated with an individual's MCV rather than iron status. The persistent elevation in sTfR 4 weeks post-infection in both malaria VIS and clinical malaria may reflect a causal link between malaria and iron deficiency. FUNDING: National Health and Medical Research Council (Program Grant 1037304, Project Grants 1045156 and 1156809; Investigator Grants 2016792 to BEB, 2016396 to JCM, 2017436 to MJG); US National Institute of Health (R01-AI116472-03); Malaysian Ministry of Health (BP00500420).
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Ferritinas , Hepcidinas , Homeostasis , Hierro , Malaria , Humanos , Femenino , Hierro/metabolismo , Hierro/sangre , Masculino , Adulto , Hepcidinas/sangre , Hepcidinas/metabolismo , Malaria/sangre , Malaria/parasitología , Malaria/metabolismo , Ferritinas/sangre , Receptores de Transferrina/metabolismo , Receptores de Transferrina/sangre , Persona de Mediana Edad , Malasia/epidemiología , Adulto Joven , Estudios Longitudinales , Malaria Falciparum/parasitología , Malaria Falciparum/sangre , Malaria Falciparum/metabolismo , Eritropoyetina/metabolismo , Eritropoyetina/sangre , Biomarcadores , Parasitemia/sangreRESUMEN
The fundamental models underlying hormonal physiological regulation and homeostasis remain poorly understood. We aimed to derive quantitative evidence regarding these models from the study of population data of balance points of different parameters and their respective controlling hormones. We studied the slopes of correlations between concentrations of circulating free thyroxine and thyrotropin, calcium and parathyroid hormone, hemoglobin and erythropoietin, and glucose and insulin in such population data, as well as the slopes of the limbs of various feedback loops estimated empirically and by reverse engineering of the population data. We used computer simulations to model the factors that influence the slopes derived from the population data, and then matched these simulations with the empirically derived slopes. Our simulations showed that changes to the population distribution of feedback loop limbs may alter the slopes of correlations within population data in specific ways. Non-random (interdependent) associations of the limbs of feedback loops may also have this effect, as well as producing discrepancies between the slopes of feedback limb loops determined experimentally and the same slopes determined by derivation from population data. Our corresponding empirical findings were consistent with the presence of such interdependence in the free thyroxine/thyrotropin, hemoglobin/erythropoietin, and glucose/insulin systems. The glucose/insulin data provided evidence consistent with increasing interdependence with age in childhood. Our findings therefore provide strong evidence that the interdependence of the limbs of feedback loops is a general feature of endocrine homeostatic regulation. This interdependence potentially bestows evolutionary homeostatic and regulatory advantages.
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Glucemia , Retroalimentación Fisiológica , Insulina , Tirotropina , Tiroxina , Humanos , Tiroxina/sangre , Retroalimentación Fisiológica/fisiología , Tirotropina/sangre , Insulina/sangre , Adulto , Masculino , Femenino , Glucemia/metabolismo , Glucemia/análisis , Simulación por Computador , Hormona Paratiroidea/sangre , Persona de Mediana Edad , Niño , Calcio/sangre , Calcio/metabolismo , Adolescente , Eritropoyetina/sangre , Modelos Biológicos , Hemoglobinas/metabolismo , Hemoglobinas/análisis , Anciano , Hormonas/sangre , Homeostasis/fisiología , Adulto JovenRESUMEN
An absolute erythrocytosis is present when the red cell mass is greater than 125% of the predicted. This is suspected when the hemoglobin or hematocrit is above the normal range. An erythrocytosis can be classified as primary or secondary and congenital or acquired. The commonest primary acquired disorder is polycythemia vera. The diagnostic criteria for PV have evolved over time and this is the main diagnosis managed in hematology clinics. There are a variety of rare congenital causes both primary and secondary. In particular in young patients and/or those with a family history a congenital cause is suspected. There remains a larger cohort with acquired erythrocytosis mainly with non-hematological pathology. In order to explore for a cause of erythrocytosis, measurement of the erythropoietin level is a first step. A low erythropoietin level indicates a primary cause and a normal or elevated level indicates a secondary etiology. Further investigation is then dictated by initial findings and includes mutational testing with PCR and NGS for those in whom a congenital cause is suspected. Following this possibly bone marrow biopsy, scans, and further investigation as indicated by history and initial findings. Investigation is directed toward the identification of those with a hematological disorder which would be best managed following guidelines in hematology clinics and referral elsewhere in those for whom there are non-hematological reasons for the elevated hemoglobin.
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Policitemia , Humanos , Policitemia/diagnóstico , Policitemia/congénito , Policitemia/genética , Policitemia/sangre , Eritropoyetina/sangre , Hemoglobinas/análisis , Policitemia Vera/diagnóstico , Policitemia Vera/genética , Policitemia Vera/sangreRESUMEN
INTRODUCTION: Disordered iron balance and abnormal parathyroid hormone (PTH) concentrations, both prevalent in hemodialysis patients, are risk factors of erythropoietin (EPO) resistance. Few studies have evaluated the correlation between iron indices and PTH and the potential role of iron markers on the association of PTH with EPO resistance in hemodialysis population. METHODS: In this cross-sectional study of 71 maintenance hemodialysis patients, iron indices including hepcidin, ferritin, reticulocyte hemoglobin content (CHr), and transferrin saturation (TSAT) were examined. EPO responsiveness was measured as EPO resistance index (ERI). Lowess regression curves were performed to explore the correlations of iron indices, PTH, and ERI. The association between PTH and ERI was modeled using linear regressions. Potential role of iron indices on this association was examined using stratified analyses and mediation analyses. RESULTS: The average ERI value was 10.3 ± 5.3 IU w-1 kg-1 (g/dL) -1. ERI was correlated to PTH, hepcidin, CHr, and TSAT (all p < 0.05). Hepcidin and PTH were closely correlated with each other (r = 0.28, p = 0.020). Analysis by PTH categories yielded a total association effect of 2.53 (95% CI: 0.27-4.85, p = 0.027) for high PTH subgroup versus the reference low subgroup. No clinically significant interaction between iron indexes and PTH was identified. Hepcidin appeared to mediate about one-third of the total association between PTH and ERI in hemodialysis population (33.6%, p = 0.025). CONCLUSION: Iron indices and PTH levels were related to ERI values. Hepcidin appeared to be closely correlated to PTH and partly mediate the association between PTH and ERI in hemodialysis population.
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Eritropoyetina , Hepcidinas , Hierro , Hormona Paratiroidea , Diálisis Renal , Humanos , Hormona Paratiroidea/sangre , Diálisis Renal/efectos adversos , Masculino , Persona de Mediana Edad , Eritropoyetina/sangre , Femenino , Estudios Transversales , Hierro/sangre , Anciano , Hepcidinas/sangre , Resistencia a Medicamentos , Adulto , Ferritinas/sangreRESUMEN
AIMS: Patients with type 2 diabetes have a 20% lower total blood volume than age- and weight-matched healthy adults, suggesting a reduced capacity to transport oxygen in this population. Intermittent hypoxia, consisting of alternating short bouts of breathing hypoxic and normoxic air, increases erythropoietin levels, the hormone regulating red blood cell production, in young and older adults. The objective of this study was to determine the effect of a single session of intermittent hypoxia on erythropoietin levels and hemoglobin mass, the absolute mass of hemoglobin contained in red blood cells, in patients with type 2 diabetes. METHODS: Ten patients with type 2 diabetes were exposed to an intermittent hypoxia protocol consisting of eight 4-min cycles at a targeted oxygen saturation of 80% interspersed with normoxic cycles to resaturation. Erythropoietin and hemoglobin mass responses to intermittent hypoxia in patients with type 2 diabetes were compared to previously published data from an identical intermittent hypoxia protocol performed in age-matched older adults. RESULTS: Intermittent hypoxia increased erythropoietin levels in older adults but did not induce any change in erythropoietin levels in patients with type 2 diabetes (3.2 ± 2.2 vs. 0.2 ± 2.7 mU/ml, p = 0.01). Hemoglobin mass indexed to body weight was 21% lower in patients with type 2 diabetes than in older adults (8.1 ± 1.7 vs. 10.2 ± 2.1 g/kg, p < 0.01). CONCLUSIONS: These findings suggest an impaired erythropoietin response to decreased oxygen levels in patients with type 2 diabetes, which may contribute to the reduced oxygen transport capacity observed in this population.
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Diabetes Mellitus Tipo 2 , Eritropoyetina , Hipoxia , Humanos , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/fisiopatología , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/sangre , Eritropoyetina/sangre , Eritropoyetina/metabolismo , Masculino , Femenino , Hipoxia/fisiopatología , Hipoxia/metabolismo , Persona de Mediana Edad , Anciano , Hemoglobinas/metabolismo , Hemoglobinas/análisis , Oxígeno/metabolismo , Oxígeno/sangreRESUMEN
According to the current treatment recommendations, anagrelide, an oral antiplatelet agent, is recommended as a second-line therapy for patients with high-risk essential thrombocythemia experiencing intolerance or refractoriness to first-line approach, such as hydroxyurea or pegylated interferon alpha-2a. If there is a need for introduction of cytoreductive treatment in young patients with a perspective of lifelong exposure, both the efficacy and long-term outcomes should be known. We present the analysis of 48 young patients, diagnosed with essential thrombocythemia below the age of 60, who were exposed to anagrelide treatment for over 10 years. Our observations show that the highest proportion of complete remissions without adverse events and disease progression is seen in the JAK2-mutated patients. By evaluating the changes in hemoglobin concentration and serum erythropoietin throughout the study, we were able to reveal the development of progressive anemia, resulting from diminished susceptibility to erythropoietin and unrelated to bone marrow fibrosis, in patients harboring CALR mutation. Additionally, occurrence of new bone marrow fibrosis was confirmed in seven JAK2-unmutated patients at the end of the study. In summary, in young patient population, we recommend limiting the use of anagrelide to JAK2-mutated subgroup, reducing exposure time and underline the importance of periodic monitoring for the presence of bone marrow fibrosis.
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Inhibidores de Agregación Plaquetaria , Mielofibrosis Primaria , Quinazolinas , Trombocitemia Esencial , Niño , Humanos , Eritropoyetina/sangre , Inhibidores de Agregación Plaquetaria/uso terapéutico , Mielofibrosis Primaria/tratamiento farmacológico , Mielofibrosis Primaria/genética , Quinazolinas/uso terapéutico , Trombocitemia Esencial/tratamiento farmacológico , Trombocitemia Esencial/genéticaRESUMEN
Inflammatory states are associated with anemia of chronic disease and acute infection. Hepcidin, a regulator of iron metabolism, is involved in iron pathophysiology during inflammation. We investigated biochemical characteristics in children with anemia from different causes. Four patient groups (n = 38; mean age: 12.44 ± 4.35 years) were studied: (1) inflammatory bowel disease (IBD, 10 patients); (2) iron deficiency anemia (IDA, 12); (3) celiac disease (CD, 8); (4) acute infection (AI, 8). Laboratory measurements were evaluated at diagnosis: blood count, serum iron, transferrin, ferritin, vitamin B12, folic acid, CRP, erythropoietin, hepcidin and soluble transferrin receptor (sTfR). IDA patients had the lowest Hgb (6.9 ± 1.7 g/dL), MCV (63.2 ± 7.2 fL), iron (16.8 ± 13.5 µg/dL), ferritin (4.5 ± 4.5 ng/mL) and hepcidin (3.1 ± 0.8 ng/mL) values, and the highest transferrin and sTfR values. AI patients had the highest ferritin (156.2 ± 124.5 ng/mL), CRP (144.6 ± 94 mg/L) and hepcidin (74.67 ± 12.3 ng/ml) values. Overall, hepcidin levels correlated with CRP and with ferritin (r = 0.83 and 0.85, respectively). Elucidating specific etiology-related biochemical profiles in pediatric patients with anemia from different causes using a combination of laboratory biomarkers, including hepcidin, can help physicians treat the anemia.
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Anemia/sangre , Anemia/diagnóstico , Adolescente , Anemia/complicaciones , Anemia Ferropénica/sangre , Anemia Ferropénica/complicaciones , Biomarcadores/sangre , Proteína C-Reactiva/metabolismo , Enfermedad Celíaca/sangre , Enfermedad Celíaca/complicaciones , Niño , Eritropoyetina/sangre , Femenino , Ferritinas/sangre , Ácido Fólico/sangre , Hemoglobinas/metabolismo , Hepcidinas/metabolismo , Humanos , Infecciones/sangre , Infecciones/complicaciones , Enfermedades Inflamatorias del Intestino/sangre , Enfermedades Inflamatorias del Intestino/complicaciones , Hierro/análisis , Hierro/sangre , Masculino , Receptores de Transferrina/sangre , Transferrina/metabolismo , Vitamina B 12/sangreRESUMEN
We assessed the diagnostic performances of erythropoietin and JAK2 mutations in 1,090 patients with suspected polycythemia who were referred for red cell mass (RCM) measurement. In patients with a high haematocrit and/or haemoglobin level, a low erythropoietin level (<=3·3 mUI/ml) and JAK2 mutation showed comparable positive predictive value (PPV) for true polycythemia (RCM>=125%), 92·1% and 90% respectively. A very-low erythropoietin level (<=1·99 mUI/ml) had a PPV of 100% for polycythemia vera (PV) diagnosis. We confirmed the correlations between RCM, erythropoietin and JAK2 variant allelic frequency in PV patients. This study prompts the need to revisit the role of EPO in PV diagnostic criteria.
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Eritropoyetina/sangre , Janus Quinasa 2/genética , Mutación , Policitemia Vera/sangre , Policitemia Vera/genética , Alelos , Sustitución de Aminoácidos , Toma de Decisiones Clínicas , Manejo de la Enfermedad , Índices de Eritrocitos , Volumen de Eritrocitos , Frecuencia de los Genes , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Humanos , Volumen Plasmático , Policitemia Vera/diagnóstico , Policitemia Vera/epidemiología , Sensibilidad y EspecificidadRESUMEN
This study aims to establish the isolation and purification method of polysaccharides from medicinal residue of Panax notoginseng (PPN). The structure and protective effect of PPN on myelosuppression mice were investigated. One neutral polysaccharide (NPPN) and five acidic polysaccharides (APPNâ I, APPNâ II-A, APPNâ II-B, APPNâ III-A, and APPNâ III-B) were obtained. The results confirmed that NPPN, APPNâ I and APPNâ II-A are glycan with 1, 4 main chains. APPNâ III-A is a glycan. APPNâ II-B and APPNâ III-B are homogalacturonan pectin with 1, 4 main chains. This study demonstrated that NPPN played a bone marrow protective role in myelosuppression mice induced by cyclophosphamide. NPPN could relieve cell cycle arrest, reduce the apoptosis rate of marrow cells, and improve granulocyte-macrophage colony-stimulating (GM-CSF), thermoplastic polyolefin (TPO) and erythropoietin (EPO) serum level, which contributes to promoting the proliferation of hematopoietic cells.
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Células de la Médula Ósea/efectos de los fármacos , Ciclofosfamida/farmacología , Panax notoginseng/metabolismo , Polisacáridos/química , Animales , Apoptosis/efectos de los fármacos , Células de la Médula Ósea/citología , Células de la Médula Ósea/metabolismo , Puntos de Control del Ciclo Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Eritropoyetina/sangre , Femenino , Factor Estimulante de Colonias de Granulocitos y Macrófagos/sangre , Células Madre Hematopoyéticas/citología , Células Madre Hematopoyéticas/metabolismo , Metilación/efectos de los fármacos , Ratones , Polisacáridos/aislamiento & purificación , Polisacáridos/farmacologíaRESUMEN
The molecular mechanism that regulates iron homeostasis is based on a network of signals, which reflect on the iron requirements of the body. HFE-related hemochromatosis is characterized by excessive intestinal absorption of dietary iron, in particular cases resulting in pathologically high iron storage in tissues and organs. During childhood, HFE gene homozygosity or heterozygosity manifests exclusively in the form of biochemical abnormalities. Because of their mutual link, bioavailable iron and endogenous erythropoietin (EPO) are indispensable for effective erythropoiesis. We analyzed the impact of p.(His63Asp) polymorphism of the HFE gene on erythropoiesis taking into consideration endogenous EPO production in the developmental age. In the study we performed, we observed a significant, strong and negative correlation between the concentration of EPO, hemoglobin, and red blood cell count. A negative trend was also noted on the impact of iron concentration and transferrin saturation on EPO production. In conclusion, this preliminary study demonstrates an impaired impact of endogenous EPO on erythropoiesis in the presence of increased iron content in carriers of p.(His63Asp) (heterozygotes) variant of the HFE gene in developmental age.
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Eritropoyetina/sangre , Proteína de la Hemocromatosis/genética , Hemocromatosis , Mutación Missense , Polimorfismo Genético , Adolescente , Sustitución de Aminoácidos , Eritropoyetina/genética , Hemocromatosis/sangre , Hemocromatosis/genética , Proteína de la Hemocromatosis/metabolismo , Humanos , MasculinoRESUMEN
INTRODUCTION: Erythropoiesis stimulating agents (ESAs) represents the principal treatments for anemia in patients with lower-risk myelodysplastic syndromes (MDS). Pre-treatment erythropoietin (EPO) level and previous blood transfusion requirement are the two major predictors for response to ESAs. However, most evidence was derived from Western countries whereas there have been limited data in patients with Asian background. METHODS: We retrospectively collected data on patients with low-risk MDS who received ESAs. Erythroid response was evaluated according to IWG 2006 criteria. MDS subtypes, r-IPSS, baseline hemoglobin (Hb), ESAs dosage and erythropoietin level were reviewed from medical records. Gene mutations were analyzed in patients' blood or bone marrow at diagnosis by 40-gene myeloid panel targeted sequencing. Clinical and laboratory parameters were compared between erythroid responder and non-responder groups. RESULTS: A total of 47 patients were recruited in the study. The median age at diagnosis of the patients in this cohort was 77 years (IQR, 70-83) and 44.7% were male. The median revised international prognostic scoring system (R-IPSS) score of patients was 2.5. Response rate to ESAs was 46.8% (22/47). Median EPO level in responders was significantly lower than non-responders (27.7 vs. 59.1 U/L, p=0.02). Median ESAs dosage in responder group was 30,000 units per week. Cytogenetic abnormalities were detected in 27.3% and 24% of the responder and non-responder groups, respectively. Of 22 patients with available 40 gene mutation targeted sequencing, ASXL1, IDH2 and TET2 represented the 3 most common mutations and were found in 22%, 22% and 17%, respectively. There were no differences in cytogenetic abnormalities and gene mutations between groups. Patients who responded to ESAs showed a higher 5-year overall survival (OS) compared to non-responders (5-year OS 75% vs. 60.9%; p=0.008). CONCLUSION: We conclude that a low serum EPO level is a predictive factor for responsiveness to ESAs in Asian patients with low-risk MDS.
Asunto(s)
Pueblo Asiatico/genética , Eritropoyetina/sangre , Hematínicos/uso terapéutico , Síndromes Mielodisplásicos/sangre , Síndromes Mielodisplásicos/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Anemia/sangre , Anemia/tratamiento farmacológico , Anemia/genética , Transfusión Sanguínea/estadística & datos numéricos , Aberraciones Cromosómicas/efectos de los fármacos , Proteínas de Unión al ADN/genética , Dioxigenasas/genética , Femenino , Humanos , Isocitrato Deshidrogenasa/genética , Masculino , Mutación , Síndromes Mielodisplásicos/genética , Valor Predictivo de las Pruebas , Pronóstico , Proteínas Represoras/genética , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
Abnormally high serum ferritin levels have been reported during pediatric ECMO, attributed to frequent red blood cell transfusion and suggestive of iron overload. However, the utility of ferritin for diagnosing iron overload is complicated by its response as an acute-phase reactant. In this study, we aimed to assess the utility of ferritin for diagnosing ECMO-related iron overload, with secondary aims of understanding its relationship with inflammation and erythropoiesis. Ferritin was elevated in all pediatric ECMO runs (median 459 ng/ml, IQR = 327.3-694.4). While intermittent elevations in serum iron were observed, all normalized prior to decannulation. Unreported previously, erythropoietin (EPO) remained well above normative values prior to and throughout ECMO runs, despite frequent transfusion and exposure to hyperoxia. Ferritin correlated poorly with serum iron [r(80) = 0.05, p = 0.65], but correlated well with IL-6 [r(76) = 0.48, p < 0.001] and EPO [r(81) = 0.55, p < 0.001]. We suggest that serum ferritin is a poor biomarker of iron overload in ECMO patients, and that future investigation into its relationship with EPO is warranted.
Asunto(s)
Oxigenación por Membrana Extracorpórea , Ferritinas/sangre , Sobrecarga de Hierro/sangre , Preescolar , Eritropoyetina/sangre , Oxigenación por Membrana Extracorpórea/efectos adversos , Humanos , Lactante , Recién Nacido , Hierro/sangre , Sobrecarga de Hierro/diagnóstico , Sobrecarga de Hierro/etiología , Proyectos Piloto , Estudios ProspectivosRESUMEN
OBJECTIVE: High serum erythropoietin (EPO) levels have been reported in adult patients with obstructive sleep apnea (OSA), however there is a lack of related literature in children with OSA. The main objective of this study was to explore the potential use of EPO as a pediatric OSA biomarker by exploring the relationship between serum EPO levels and the presence of pediatric OSA. METHODS AND MATERIALS: A prospective study was conducted on children (4-12 years old) referred for overnight PSG. Thirty (30) consecutive children with mild. 30 consecutives with moderate, and 30 consecutives with severe OSA (OSA group), as well as 30 consecutive children with AHI≤1 (non-OSA group) were recruited. Morning blood specimens after PSG studies were obtained in order to compare EPO levels. RESULTS: Finally, 115 children included for analysis. Non-OSA group consisted of 29 children (mean age: 6.93 ± 2.10) and OSA-group of 86 children (mean age: 6.78 ± 2.53). Mean EPO values for the non-OSA and OSA groups were 5.46 ± 2.29 mIU/ml and 8.33 ± 4.10 mIU/ml respectively. OSA-group had significant higher EPO levels than non-OSA (P: 0.01) while EPO levels were significantly correlated with AHI (p < 0.001). CONCLUSION: Our study showed that serum EPO levels of children with OSA are significantly higher than those without OSA and correlate significantly with AHI. These results suggest that EPO may be considered as a biomarker candidate for pediatric OSA. Since this may be the first study on the topic further research is needed.
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Eritropoyetina , Apnea Obstructiva del Sueño , Biomarcadores , Niño , Preescolar , Eritropoyetina/sangre , Humanos , Polisomnografía , Estudios Prospectivos , Apnea Obstructiva del Sueño/diagnósticoRESUMEN
Athletes abuse recombinant human erythropoietin (rhEPO) and erythropoiesis stimulating agents to increase hemoglobin mass and improve performance. To evade detection, athletes have developed sophisticated blood doping regimens, which often include rhEPO micro-dosing. Detection of these methods requires biomarkers with increased sensitivity and a sample matrix that is more amenable to frequent testing in the field. We have developed a method to measure two immature reticulocyte proteins, CD71 and ferrochelatase (FECH), and one total erythrocyte protein, Band 3, in dried blood spots (DBS). This method was tested in response to rhEPO administration after low doses, 40 IU/kg, micro-doses, 900 IU, or saline injection in 20 healthy subjects. During administration of low-dose rhEPO, the mean CD71/Band 3 and FECH/Band 3 ratio increased by 412 ± 197% and 250 ± 44%, respectively. The mean response for the current biomarker, RET%, increased by 195 ± 35%. During administration of rhEPO micro-doses, CD71/Band 3 increased to 127 ± 25% on day 35 and 139 ± 36% on day 39, while no increase was observed in RET%. After rhEPO administration, during the washout phase, mean values decreased to a minimum of 64 ± 4% and 64 ± 11% for CD71/Band 3 and RET%, respectively. However, CD71/Band 3 remained below 75% of baseline for at least 4 weeks after rhEPO injection, while RET% returned to baseline levels. The results demonstrate that immature reticulocyte proteins have a larger response to rhEPO administration than the current biomarker, RET%, and can be monitored in the DBS matrix.