Acute exposure to carbon monoxide inhalation and/or hot water immersion transiently increases erythropoietin in females but not in males.

The use of acute carbon monoxide inhalation (COi) and hot water immersion (HWI) are of growing interest as interventions to stimulate erythropoietin (EPO) production. However, whether EPO production is further augmented when combining these stressors and whether there are sex differences in this response are poorly understood. Therefore, we measured circulating EPO concentration in response to acute COi and HWI independently and in combination and determined whether the responses were altered by sex. Participants completed three study visits-COi, HWI, and combined COi and HWI-separated by 1 week in a randomized, balanced, crossover design. Renal blood velocity was measured during all interventions, and carboxyhaemoglobin was measured during and after COi. Serum samples were analysed every hour for 6 h post-intervention for EPO concentration. HWI decreased renal blood velocity (46.2 cm/s to 36.2 cm/s) (P < 0.0001), and COi increased carboxyhaemoglobin (1.5%-12.8%) (P < 0.0001) without changing renal blood velocity (46.4-45.2 cm/s) (P = 0.4456). All three interventions increased peak EPO concentration from baseline (COi: 6.02-9.74 mIU/mL; HWI: 6.80-11.10 mIU/mL; COi + HWI: 6.71-10.91 mIU/mL) (P = 0.0048) and to the same extent (P = 0.3505). On average, females increased EPO while males did not in response to COi (females: 6.17 mIU/mL; males: 1.27 mIU/mL) (P = 0.0010), HWI (females: 6.47 mIU/mL; males: 2.14 mIU/mL) (P = 0.0104), and COi and HWI (females: 6.65 mIU/mL; males: 1.76 mIU/mL) (P = 0.0256). These data emphasize that combining these interventions does not augment EPO secretion and that these interventions may work better in females.

Evaluation of serum ferritin level and hepatitis b and hepatitis c viral infection in chronic hemodialysis patients.

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.

Effect of Single High-Dose Vitamin D3 Supplementation on Post-Ultra Mountain Running Heart Damage and Iron Metabolism Changes: A Double-Blind Randomized Controlled Trial.

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.

Analysis of the relationship between VEGF, NLRP3 inflammatory complex, EPO levels, and ocular hemodynamics in patients with primary open-angle glaucoma.

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.

Ketone monoester plus high-dose glucose supplementation before exercise does not affect immediate post-exercise erythropoietin concentrations versus glucose alone.

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% V̇O2peak) 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.

Serum Erythropoietin and Ischemic-Modified Albumin Levels in Adolescents with Obsessive-Compulsive Disorder.

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.

Longitudinal changes in iron homeostasis in human experimental and clinical malaria.

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).

Erythrocytosis: Diagnosis and investigation.

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.

Iron Indices Mediate but Not Modify Association of Parathyroid Hormone with Erythropoietin Resistance in Hemodialysis Patients.

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.

Population data evidence of interdependence of the limbs of hormonal feedback loops.

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.

A very-low-calorie ketogenic diet normalises obesity-related enhanced levels of erythropoietin compared with a low-calorie diet or bariatric surgery.

PURPOSE: Nutritional ketosis synergistically with body-weight loss induced by a very-low-calorie ketogenic diet (VLCKD) has proven to be effective in improving obesity-related pathophysiology. Recently, growing attention has been focused on the relation between erythropoietin (EPO) and obesity. Thus, this study aims to investigate whether nutritional ketosis and weight loss induced by a VLCKD modify the circulating levels of EPO in patients with obesity in comparison with the effect of low-calorie diet (LCD) or bariatric surgery (BS). METHODS: EPO levels, iron status and body composition parameters were evaluated in 72 patients with overweight or obesity and 27 normal-weight subjects at baseline and after the three different weight-reduction therapies (VLCKD, LCD and BS) in 69 patients with excess body weight. ß-hydroxybutyrate levels were also measured in the VLCKD group. The follow-up was established at 2-3 months and 4-6 months. RESULTS: It was found that EPO levels were higher in morbid obesity and correlated with higher basal weight, fat mass (FM) and fat-free mass (FFM) in the overall sample. High baseline EPO levels were also correlated with higher impact on the course of weight loss and changes in FM and FFM induced by the three weight-loss interventions. Furthermore, the VLCKD induced a decrease in EPO levels coinciding with maximum ketosis, which was maintained over time, while statistically significant changes were not observed after LCD and BS. CONCLUSION: The obesity-related increased EPO levels are restored after VLCKD intervention at the time of maximum ketosis, suggesting a potential role of the nutritional ketosis induced by the VLCKD. Baseline EPO levels could be a biomarker of response to a weight-loss therapy.

Impaired erythropoietin response to hypoxia in type 2 diabetes.

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.

Elevated hemoglobin levels in renal transplant recipients with polycystic kidney disease versus other etiologies: exploring mechanisms and implications for outcomes.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD)-related end-stage kidney disease (ESKD) often necessitates transplantation. However, the impact of ADPKD on post-transplant outcomes, specifically hemoglobin levels, remains unknown. METHODS: We retrospectively analyzed 513 Kidney Transplant Recipients (KTRs), of whom 81 had ESKD due to ADPKD (20 with pre-transplant native nephrectomy and 61 without). Hemoglobin levels were evaluated at multiple time intervals post-transplant. RESULTS: Kidney transplant recipients with ADPKD vs. KTRs with ESKD due to other causes exhibited significantly higher hemoglobin levels in repeated measurement analysis. Multivariable analyses confirmed ADPKD as an independent predictor for elevated hemoglobin levels. In a multivariable logistic regression analysis, the odds for maximum hemoglobin > 15 mg/dL at 3-12 months post-transplant were more than twice as high in ADPKD patients vs. all the other KTRs (Odds Ratio [OR] 2.31, 95% Confidence Interval [CI] 1.3-4.13, p < 0.001). Pre-transplant native nephrectomy revealed a trend toward lower hemoglobin levels. Elevated hemoglobin levels were linked to improved estimated glomerular filtration rate (eGFR) at one year post-transplant. Patient survival was enhanced among KTRs with ADPKD compared to other ESKD causes. CONCLUSIONS: Kidney transplant recipients with ADPKD exhibited elevated hemoglobin levels post-transplant, possibly due to prolonged native kidney erythropoietin production. These elevated hemoglobin levels were linked to improved outcomes, including allograft function and patient survival. Future research should further investigate the underlying mechanisms driving favorable ADPKD KTR outcomes.

Characterization of DNA concentration in urine and dried blood samples to detect the c.577 deletion within the EPO gene.

The EPO gene variant, c.577del (VAR-EPO), was discovered in the Chinese population in 2021. The mutated protein is naturally present in urine from individuals heterozygous for the variant. Electrophoresis methods currently applied in anti-doping laboratories produce a pattern in samples from individuals carrying VAR-EPO that cannot be unambiguously distinguished from individuals who received recombinant EPO doses. Consequently, the analysis of blood samples is obligatory to facilitate interpretation of suspicious findings from urine samples. However, this complicates the process and delays the reporting. Objective of this study was to develop EPO c.577del detection in urine and dried blood samples (DBS) in order to facilitate and accelerate EPO results management. Moreover, estimation of the success rate of sequencing regarding concentration of DNA in urine and DBS was evaluated. Conclusive results regarding Sanger sequencing were obtained for all samples with DNA concentrations above 0.024 ng/µL DNA in 80% of urines samples from volunteers. The potential success of DNA sequencing rate in athletes' urines was investigated. A total of 191 urine samples were considered. DNA concentration exceeding 0.024 ng/µL was detected in 85% of the samples. Interestingly, in-competition samples had a significantly higher DNA concentration than out-of-competition male urine samples (0.330 vs. 0.084 ng/µL). Moreover, conclusive EPO sequences were obtained for 100% of DBS (cellulose and polymer matrices). In conclusion, method for detection of EPO gene variant was developed in urine and DBS. Characterization of DNA concentration was performed in order to evaluate the probability of success of sequencing EPO gene in anti-doping field.

Anagrelide in essential thrombocythemia: Efficacy and long-term consequences in young patient population.

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.

Characterization of acquired anemia in children by iron metabolism parameters.

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.

Structural Characterization of Polysaccharides Isolated from Panax notoginseng Medicinal Residue and Its Protective Effect on Myelosuppression Induced by Cyclophosphamide.

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 (APPN I, APPN II-A, APPN II-B, APPN III-A, and APPN III-B) were obtained. The results confirmed that NPPN, APPN I and APPN II-A are glycan with 1, 4 main chains. APPN III-A is a glycan. APPN II-B and APPN 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.

Revisiting Diagnostic performances of serum erythropoïetin level and JAK2 mutation for polycythemias: analysis of a cohort of 1090 patients with red cell mass measurement.

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.

Erythropoietin Concentration in Boys With p.His63Asp Polymorphism of the HFE Gene.

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.