Insights into Iron Metabolism Parameters in Ischemic Stroke: A Single-Center Prospective Cohort Study.

The hemojuvelin-hepcidin regulatory axis may play a key role in the iron metabolism both systemically and locally. There is a pressing need to evaluate this tightly regulated network of iron parameters and their potential impact on the development of ischemic stroke (IS). We aimed to assess iron metabolism biomarkers in patients after IS, evaluating changes over time and considering their clinical features. We studied 45 patients diagnosed with IS. We assessed major iron metabolism parameters, such as hepcidin, soluble hemojuvelin (sHJV), soluble transferrin receptor (sTfR), and ferritin, using immunoenzymathic methods at two time points: on admission and on the 7th day post IS. We found increased ferritin levels on the 7th day post IS compared to admission, and this was observed in the entire study group (p = 0.03) and in the subgroup treated with thrombolysis (p = 0.02). The hepcidin levels, on the other hand, showed a significant decrease on the 7th day, though this difference was only evident in the entire study group (p = 0.04). We also discovered significantly elevated sHJV levels in patients with PACI stroke compared to other stroke locations, both on admission and on the 7th day post IS (p < 0.05). Significantly higher sHJV levels were observed in patients treated with thrombolysis compared to those receiving conventional treatment, regardless of the time point (p < 0.0001 and p = 0.0002, respectively). Our study revealed changes in the iron metabolism parameters during stroke. The patients with anterior cerebral infarction and those treated with thrombolysis presented significantly elevated sHJV levels.

Factor VII Activating Protease (FSAP) and Its Importance in Hemostasis-Part I: FSAP Structure, Synthesis and Activity Regulation: A Narrative Review.

Factor VII activating protease (FSAP) was first isolated from human plasma less than 30 years ago. Since then, many research groups have described the biological properties of this protease and its role in hemostasis and other processes in humans and other animals. With the progress of knowledge about the structure of FSAP, several of its relationships with other proteins or chemical compounds that may modulate its activity have been explained. These mutual axes are described in the present narrative review. The first part of our series of manuscripts on FSAP describes the structure of this protein and the processes leading to the enhancement and inhibition of its activities. The following parts, II and III, concern the role of FSAP in hemostasis and in the pathophysiology of human diseases, with particular emphasis on cardiovascular diseases.

Does ASTRAL score at hospital admission predict symptomatic haemorrhagic transformation in acute ischaemic stroke after revascularisation? A pilot single-centre study.

INTRODUCTION: Accurately predicting outcomes after acute ischaemic stroke (AIS) is a major clinical goal. The aim of this pilot study was to evaluate the prognostic validity and accuracy of the Acute Stroke Registry and Analysis of Lausanne (ASTRAL) score in predicting symptomatic haemorrhagic transformation (sHT) in patients with AIS who have undergone revascularisation. MATERIAL AND METHODS: Consecutive patients hospitalised for AIS who underwent treatment with intravenous thrombolysis (IVT) and/or mechanical thrombectomy (MT) were identified, and their ASTRAL scores at hospital admission were estimated. The study endpoint was sHT within 24 hours of stroke onset. The predictive performance of the ASTRAL score was investigated through logistic regression analysis and discrimination and calibration tests. RESULTS: Sixty-eight AIS patients, with a median age of 69 (58-79) years, were included. sHT occurred in 20 (29.4%) of the 68 patients. The ASTRAL score was significantly higher in patients who developed sHT compared to non-sHT patients [36 (34-38) versus 24 (17-32); p<0.001]. The ASTRAL score was an independent predictor of sHT, and showed good discriminative power (area under the curve 0.88; 95% confidence interval, 0.789-0.965). CONCLUSIONS AND CLINICAL IMPLICATIONS: ASTRAL score is an independent predictor of sHT and shows high predictive accuracy in patients with AIS. Future studies are warranted to confirm these results.

Immunological and Hematological Response in COVID-19.

INTRODUCTION: Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has recently and rapidly emerged and developed into a global pandemic. Through the renin-angiotensin system, the virus may impact the lung circulation, but the expression on endothelium may conduct to its activation and further systemic damage. While precise mechanisms underlying these phenomena remain to be further clarified, the understanding of the disease, its clinical course, as well as its immunological and hematological implications is of paramount importance in this phase of the pandemic. METHODS: This review summarizes the evidence gathered until 12 June; electronic databases were screened for pertinent reports on coronavirus and inflammatory and hematological changes. Search was conducted by two independent investigators; keywords used were "SARS-CoV-2," "COVID-19," "inflammation," "immunological," and "therapy." RESULTS: The viral infection is able to trigger an excessive immune response in predisposed individuals, which can result in a "cytokine storm" that presents an hyperinflammation state able to determine tissue damage and vascular damage. An explosive production of proinflammatory cytokines such as TNF-α IL-1ß and others occurs, greatly exaggerating the generation of molecule-damaging reactive oxygen species. These changes are often followed by alterations in hematological parameters. Elucidating those changes in SARS-CoV-2-infected patients could help to understand the pathophysiology of disease and may provide early clues to diagnosis. Several studies have shown that hematological parameters are markers of disease severity and suggest that they mediate disease progression. According to the available literature, the primary hematological symptoms-associated COVID-19, and which distinguish patients with severe disease from patients with nonsevere disease, are lymphocytopenia, thrombocytopenia, and a significant increase in D-dimer levels. CONCLUSIONS: SARS-CoV-2 infection triggers a complex response altering inflammatory, hematological, and coagulation parameters. Measuring these alterations at certain time points may help identify patients at high risk of disease progression and monitor the disease severity.

COVID-19 and Extracorporeal Membrane Oxygenation.

INTRODUCTION: Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has recently and rapidly emerged and developed into a global pandemic. In SARS-CoV-2 patients with refractory respiratory failure, there may be a role for veno-venous extracorporeal membrane oxygenation (V-V ECMO) as a life-saving rescue intervention. METHODS: This review summarizes the evidence gathered until June 12, 2020; electronic databases were screened for pertinent reports on coronavirus and V-V ECMO. Search was conducted by two independent investigators; keywords used were SARS-CoV-2, COVID-19, ECMO, and extracorporeal life support (ECLS). RESULTS: Many patients with COVID-19 experience moderate symptoms and a relatively quick recovery, but others must be admitted into the intensive care unit due to severe respiratory failure and often must be mechanically ventilated. Further deterioration may require institution of extracorporeal oxygenation. Infection mechanisms may trigger "cytokine storm," an inflammatory disorder notable for multi-organ system failure; together with other metabolic and hematological changes, these amplify the changes pertinent to ECMO therapy, often exaggerating blood coagulation disorders. Thirty-two studies were found describing experiences with ECMO in the treatment of COVID-19. Of 4,912 COVID-19 patients, 2,119 (43%) developed ARDS and 2,086 (42%) were transferred to the ICU; 1,015 patients (21%) were treated with ECMO. While in an overall cohort, observed mortality was 640 (13%), the mortality within ECMO subgroups reached up to 34.6% (range 0-100%). CONCLUSION: The efficacy of ECMO treatment for COVID-19 is largely dependent on the expertise of the center in ECLS due to the interplay between the changes in hematological and inflammatory modulators associated with both COVID-19 and ECMO. In order to support gas exchange during early infection with SARS-CoV-2, ECMO has a strong rationale for the treatment of the most critically ill patients. Due to the limited resources during a global pandemic, ECMO should be reserved for only the most severe cases of COVID-19.

Female Volleyball Players Are More Prone to Cortisol Anticipatory Stress Response than Sedentary Women.

Background and Objectives: Top-level sports performance places heavy physical and psychological demands on elite-level athletes, which can be a source of increased levels of stress. Therefore, high-level volleyball players may present altered cardiovascular and endocrinological stress response during stressful events. Although many previous studies have examined the response to stress on athletes, most of them regarded only males, while the impact of the female menstrual cycle has rarely been taken into account. We aimed to study psychophysiological response to anticipatory stressor through analysis of heart rate, self-reported anxiety level, and salivary cortisol in healthy young female athletes by minimalizing the effect of confounders. Materials and Methods: A total of 55 females (25 members of the best league for female volleyball players in Poland and 30 sedentary-lifestyle control subjects) in the follicular phase of their menstrual cycle were exposed to mental arithmetic tasks as an experimental imitation of the stressor. Volleyball players were significantly taller than sedentary individuals (177.1 ± 3.4 cm vs. 173.3 ± 3.4 cm, respectively, p = 0.034), but did not differ in weight (73.6 ± 5.2 kg vs. 70 ± 4.23 kg, respectively, p = 0.081), body mass index (BMI) (23.5 ± 1.13 vs. 24.1 ± 1.45, respectively, p = 0.060), and age (22 ± 1.11 vs. 23 ± 1.14 years, respectively, p = 0.2). Their stress responses were assessed through self-reported anxiety levels and physiological measurements of salivary cortisol concentrations and heart rate (HR). Results: For HR, significant effects of time (F(2,120) = 21.34, p < 0.001, η2 = 0.26) were found, but not for training status (F(1,60) = 2.69, p = 0.106, η2 = 0.04). For cortisol levels, the analysis showed the main effects of time (F(3,180) = 11.73, p < 0.001, η2 = 0.16) and training status (F(1,60) = 4.69, p = 0.034, η2 = 0.07) and a significant interaction between training status and time (F(3,180) = 3.07, p = 0.029, η2 = 0.05). Post-hoc analyses showed higher cortisol concentrations among volleyball players following the math task (all p < 0.001), as well as higher cortisol concentrations in S2, S3, and S4 compared to S1 in volleyball players (all p < 0.001). We observed also a significant increase in state anxiety in both groups (all p < 0.001), but no differences in state anxiety levels between groups. Conclusion: Female volleyball players may not differ in subjective graduation of stressors; however, exposure to training-based stressors seems to promote cortisol response to the anticipated stressor.

Association of Neutrophil-to-Lymphocyte Ratio and Lymphocyte-to-Monocyte Ratio with Treatment Modalities of Acute Ischaemic Stroke: A Pilot Study.

Background and Objectives: Ischaemic stroke (IS) is the leading cause of death and disability worldwide. All stages of cerebral ischaemia, but especially acute phase, are associated with inflammatory response. Recent studies showed that neutrophil-to-lymphocyte ratio (NLR) and lymphocyte-to-monocyte ratio (LMR) may be used to assess inflammation in IS. To test whether there is a relationship between these parameters and type of stroke treatment, we analysed NLR and LMR in IS patients treated with three different modalities. Materials and Methods: The study included 58 adults with acute IS. A total of 28 patients received intravenous thrombolysis. In another 10 patients, the thrombolytic therapy was followed by thrombectomy and 20 patients did not undergo causal treatment. Blood samples were obtained within 24 h of the stroke diagnosis to calculate NLR and LMR. Next, NLR and LMR of the study subgroups were compared. Results: Our study revealed that NLR was significantly higher in patients treated with thrombectomy following thrombolysis, compared to no causal treatment. Statistical analysis demonstrated that patients with high National Institutes of Health Stroke Scale (NIHSS) scores presented higher NLR than in those with low NIHSS scores. Additionally, patients with high-sensitivity C-reactive protein (hs-CRP) ≥ 3 mg/L presented with significantly higher NLR and significantly lower LMR than the group of patients with lower hs-CRP (<3 mg/L). Conclusions: The main finding of this pilot study was that NLR in IS patients treated using thrombectomy following thrombolysis was markedly higher than that in other treatment groups, which was associated with increased severity of the disease in these patients. Therefore, patients with higher NLR may be expected to have more severe stroke. The link between stroke severity and NLR deserves further study.

Bone morphogenetic protein 6-a possible new player in pathophysiology of heart failure.

Derangement of bone morphogenetic protein (BMP) signalling was observed in cardiovascular disorders. The present study assesses the diagnostic and prognostic value of BMP6 plasma concentration in chronic heart failure (CHF). 130 CHF patients and 32 controls participated in the study. BMP6 plasma level was measured at baseline. During 12-month follow-up death and hospitalisation with CHF exacerbation were recorded. BMP6 was significantly increased in CHF patients with highest concentration in most advanced disease. Individuals with pulmonary congestion or peripheral oedema had higher levels of BMP6 than isovolemic patients. BMP6 was not a predictor of all-cause mortality or CHF hospitalisation. BMP6 may be involved in pathophysiology of systolic CHF. BMP6 plasma level is related to the disease severity and signs of exacerbation.

A Pilot Study of Tissue Factor-Tissue Factor Pathway Inhibitor Axis and Other Selected Coagulation Parameters in Broiler Chickens Administered in Ovo with Selected Prebiotics*.

The tissue factor (TF) - tissue factor pathway inhibitor (TFPI) axis plays a major role in hemostasis. Disorders of the coagulation system are commonly diagnosed with the help of screening tests such as prothrombin time (PT), activated partial thromboplastin time (aPTT), and plasma fibrinogen concentration (PFC). However, the effect of prebiotics on the hemostasis system has not been characterized in poultry yet. This study was designed to determine the effect of in ovo administration ofprebiotics on blood coagulation parameters of broiler chickens depending on their age. The study was conducted with 180 broiler chick embryos, the air cells of which were injected on day 12 of incubation with prebiotics (experimental groups: Bi2tos, DiNovoo and RFO) or physiological saline solution (control group). At 1, 21 and 42 days of rearing, blood was sampled from 15 broiler chickens from each group. An enzyme immunoassay was performed to determine plasma TF and TFPI levels, and PT, aPTT and PFC were determined in the chicken blood. We demonstrated that: 1) total TF levels increased with age in the experimental groups, 2) prebiotics had no significant effect on TF levels between the groups at a particular age, 3) total TFPI levels differed between both the type of in ovo injected substance and the broiler chicken age, 4) in the control group, PT and aPTT were found to increase with age whilst fibrinogen concentration decreased. The main conclusion from this pilot study is that total TF and TFPI levels change with age, however no clear patterns regarding TFPI were detected yet. The levels of PT, aPTT and PFC varied with the prebiotics administered in ovo as well as with the age of broiler chickens.

Hepcidin Levels Are Increased in Patients with Acute Ischemic Stroke: Preliminary Report.

BACKGROUND: Our current understanding of iron balance in acute ischemic stroke (AIS) is still limited. The objective of this study was to evaluate levels of iron homeostasis proteins-hepcidin (25-amino acid form) and soluble hemojuvelin (sHJV) together with hepcidin/sHJV ratio (Hepc/sHJV) and soluble transferrin receptor (sTfR) in patients with AIS. In addition, the effect of timing of blood collection, type of stroke treatment, and scores on the National Institutes of Health Stroke Scale were investigated. METHODS: Participants comprised 31 patients diagnosed with AIS and 20 matched healthy controls. Venous blood samples were drawn on the first day and on the seventh day after stroke onset. Individuals who had experienced a stroke were subdivided according to type of treatment (thrombolysis group, n = 12 versus nonthrombolysis group, n = 19). Plasma hepcidin, sHJV, and sTfR levels were determined by the enzyme-linked immunosorbent assay method. RESULTS: We found that plasma hepcidin levels were significantly higher in ischemic stroke patients compared with the control group (median, 19.82 versus 12.62 ng/mL, P = .04). Furthermore, levels of hepcidin on the seventh day (1 week after diagnosis) were significantly higher in patients treated with thrombolysis than in patients not treated with thrombolysis (median, 22.16 versus 16.21 ng/mL, P = .04). CONCLUSIONS: The study provides evidence that AIS is associated with increased hepcidin levels. Stroke treatment may have an influence on hepcidin synthesis.

The Usefulness of Factor XIII Concentration Assessment in Patients in the Acute Phase of Ischaemic Stroke Treated with Thrombolysis.

BACKGROUND AND AIMS: In recent years, there has been a growing interest in factor XIII in ischaemic stroke. The study's main aim was to assess the usefulness of factor XIII concentration determination in patients with acute ischaemic stroke (AIS) treated with thrombolysis with recombinant tissue plasminogen activator (t-PA). METHODS: The study was conducted in two groups of 84 patients with AIS: group I-with thrombolytic therapy and group II-without thrombolysis. A physical examination, neurological status (using the National Institutes of Health Stroke Scale, NIHSS), daily patients' activities measured with the Barthel Index and Modified Rankin Scale (mRS), and blood parameters were conducted on day 1 and day 7. The following parameters were assessed: highly sensitive C-reaction protein (CRP), fibrinogen, D-dimers (DD), neutrophil-lymphocyte ratio (NLR index), and the concentration of factor XIII-A. RESULTS: In group I, the concentration of XIII-A decreased significantly between day 1 and 7 (p < 0.001). In group I, the concentration of XIII-A on day 7 in Total Anterior Circulation Infarct (TACI) was significantly lower than in non-TACI stroke. XIII-A concentration in group I was significantly lower in patients < 31 points with Acute Stroke Registry and Analysis of Lausanne (ASTRAL). A greater decrease in XIII-A between the first sampling on day 1 and the second sampling on day 7 was associated with a worse patient neurological state in group I. CONCLUSIONS: In patients with AIS treated with t-PA, factor XIII concentrations decrease in the acute phase of stroke, and the largest decrease occurs in the TACI stroke. Determination of factor XIII concentration in patients with AIS can be used in clinical practice as an additional parameter supporting the assessment of stroke severity and may play a role in the prognosis; lower factor XIII-A activity may be a predictor of a worse prognosis.

Ability to determine the desferrioxamine-chelatable iron fractions of nontransferrin-bound iron using HPLC.

Iron is an essential element in human development. It is imperative for oxygen and electron transport and also for DNA and neurotransmitters synthesis. On the other hand, this metal is able to participate in Fenton's reaction that in turn leads to free radical damage. The most toxic fraction of iron - nontransferrin-bound iron and its part desferrioxamine-chelatable iron - can serve as an exquisite biomarker in the identification of iron imbalance. The goal of the present study was to devise a simple, repeatable, and inexpensive method for the determination of desferrioxamine-chelatable iron in serum blood samples. The assay procedure is based on desferrioxamine complex formation with iron ions followed to ferrioxamine and its quantitative measurement using RP-HPLC method. The desferrioxamine-chelatable iron was extracted from blood by centrifugation and SPE method. Chromatographic separation was performed at 40°C by step-form gradient elution using Cadenza CD-C18 column (150 × 4.6 mm id, particle size of 3.0 µm) connected with precolumn for contaminants removal. Gradient HPLC elution has been carried out with solvent A (10 mM Tris-HCl, pH 5.5) and solvent B (ACN). The flow rate was 1.2 mL/min, and the total separation time was 5 min. The linear quantitation range was 2.5-500 µM (r = 0.9973), and the LOD and LOQ were 0.42 and 1.29 µM, respectively. Proposed HPLC method allowed for the determination of desferrioxamine-chelatable iron fraction's of nontransferrin-bound iron, both in the buffer and the serum supplemented with iron ions as well as in the patients' serum samples with good results of precision and recovery. The developed method found to be sufficiently precise and reproducible for established conditions and after validation and may be used for routine assay of desferrioxamine-chelatable iron in biological samples.

The Effect of Craniosacral Therapy on Blood Levels of Stress Hormones in Male Firefighter Cadets: A Randomized Clinical Trial.

(1) Background: Fire department cadets preparing to become firefighters and paramedics experience high levels of stress when participating in incidents like traffic accidents and fires. Stress adversely affects health, and coping with it proves difficult. Unfortunately, there is no single method that reduces stress completely in humans. One non-invasive method for lowering stress hormone levels is craniosacral therapy. (2) Methods: Fifty-seven firefighting cadets aged 18-24 years (21.63 ± 1.41) participated in the study. They were randomly assigned to either a test group or a control group. Participants' blood levels of cortisol and CRH (corticotropin-releasing hormone) were assessed before and after the study. The study group underwent 5-week craniosacral therapy (1× per week). (3) Results: The Kruskal-Wallis test showed that the therapy group's results were statistically significant for CRH values (p-value = 0.00067) and for cortisol values (p-value ≤ 0.0001). Wilxocon and Dunn tests showed statistical significance for cortisol after CS therapy between the control and study groups (p = 0.0377), and for CRH between the control and study groups before (p = 0.00634) and after the study (p = 0.000887), and in the study group before and after the study (p = 0.0101). (4) Conclusions: The application of craniosacral therapy reduced stress hormone levels in male firefighter cadets. The results indicate that craniosacral therapy (five sessions, one per week) has an effect on the reduction of stress hormones.

Soluble Hemojuvelin and Ferritin: Potential Prognostic Markers in Pediatric Hematopoietic Cell Transplantation.

OBJECTIVE: Iron overload (IO) is a common and life-threatening complication resulting from the therapy of AL and HCT patients. This study aimed to evaluate the prognostic value of 12 serum biomarkers of iron metabolism in pediatric patients treated for AL or undergoing HCT. PATIENTS: Overall, 50 patients with AL after intensive treatment and 32 patients after HCT were prospectively included in the study. AL patients at diagnosis and healthy controls served as reference groups. METHODS: The impact of the following 12 serum iron metabolism parameters on the outcome of AL/HCT patients was analyzed: iron, transferrin (Tf), total iron-binding capacity (TIBC), ferritin, ferritin heavy chains (FTH1), ferritin light chains (FTL), hepcidin, soluble hemojuvelin (sHJV), soluble ferroportin-1 (sFPN1), erythroferrone (ERFE), erythropoietin (EPO), and soluble transferrin receptor (sTfR). RESULTS: With a median follow-up of 2.2 years, high levels of ferritin and low levels of sHJV had an adverse prognostic impact on OS and EFS in children after HCT. If these patients were combined with those with AL after intensive chemotherapy, the results were confirmed for OS and EFS both for ferritin and sHJV. CONCLUSIONS: Among the 12 analyzed serum parameters of iron metabolism, increased levels of ferritin and decreased levels of sHJV had an adverse prognostic impact on survival in children after HCT. More data are needed to clarify the relationship between ferritin, sHJV, and mortality of AL children after intensive chemotherapy, and more extensive prospective studies are required to prove sHJV predictivity.

[Iron metabolism and maternal-fetal iron circulation]. / Metabolizm zelaza z zagadnieniami matczyno-plodowego krazenia zelaza.

Iron is an essential micronutrient for the proper functioning of most organisms. This element is used in oxygen transport, myelin and neurotransmitters synthesis, cell cycle and synthesis of nucleic acids. The importance of iron in the maturation of lymphocytes and proper functioning of the eye is also stressed. Newborns are particularly sensitive to imbalances in iron metabolism. Iron deficiency during pregnancy carries serious clinical consequences. It seems that a key role in the transport of iron between mother and fetus is plays by hepcidin and, described in 2010 zyklopen. The physiological role of proteins involved in iron metabolism and transport of this metal by the placenta are described in this paper. 

Caffeine and alcohol - Friends or foes of human iron stores?

BACKGROUND & AIMS: There is clear evidence that lifestyle factors affect iron bioavailability. However, information regarding the effect of alcohol and caffeine consumption on iron metabolism is limited. The aim of the current study was to evaluate the effect of caffeine and alcohol consumption on iron metabolism in healthy men, regarding their everyday physical activity level. METHODS: The study enrolled 83 men (59 physically active and 24 sedentary men) aged 18-32 years. Fasting blood samples were collected. ELISA kits were used to determine levels of ferritin, soluble transferrin receptor, hepcidin, hemojuvelin, and C-reactive protein (hsCRP). Level of physical activity was assessed using the International Physical Activity Questionnaire (IPAQ). Caffeine and alcohol intake was assessed using a food frequency questionnaire. A general linear model was performed to evaluate the relationship between caffeine intake and levels of serum ferritin, ferritin, soluble transferrin receptor, hepcidin, hemojuvelin, and hsCRP. RESULTS: Physically active men (but not sedentary men) who consumed alcohol in excess presented higher ferritin levels when compared to moderate drinkers and abstainers (R2 = 0.35, p = 0.0001). Heavy drinkers presented the highest hepcidin levels when compared to both abstainers and moderate drinkers (p < 0.0001 for physically active, and p = 0.0267 for sedentary men). However, moderate drinkers showed significantly lower hsCRP levels when compared to heavy drinkers and abstainers drinkers (p < 0.0001 for physically active, and p = 0.0116 for sedentary men). Greater caffeine intake was generally associated with greater serum hepcidin levels, with the strongest effect on moderate drinkers. A significant influence of caffeine intake on hsCRP was shown for physically active men but not for sedentary men - greater caffeine intake was connected with higher hsCRP levels for participants who drank alcohol. CONCLUSION: Based on the presented results it can be assumed that high caffeine consumption may lead to suppression of iron bioavailability through increased inflammation. Furthermore, physical activity and moderate alcohol consumption seemed to benefit reduction of inflammatory response, at least as represented by hsCRP levels.

[Serum prohepcidin and other iron metabolism parameters in healthy adults]. / Ocena stezenia prohepcydyny na tle wybranych parametrów gospodarki zelazem w surowicy krwi ludzi zdrowych.

UNLABELLED: Hepcidin is a newly discovered iron metabolism regulator. It decreases iron absorption from the duodenal enterocytes and inhibits its release from the reticuloendothelial macrophages. The experiments on hepcidin and its precursor--prohepcidin seem very promising and underline the need to establish the reference intervals for these proteins and define the effects of age and sex on their concentrations. AIM: The aim of this study was to assess the impact of age and sex on serum prohepcidin concentration in healthy adults. MATERIAL AND METHODS: The study group consisted of 79 healthy volunteers (F-29, M-50) between 18 to 88 years of age. Healthy adults were divided into three groups according to age: group 1-33 healthy volunteers aged between 18-36, group 2-20 healthy volunteers aged between 38-53, group 3- 26 healthy volunteers aged between 58-88. Prohepcidin and ferritin concentrations were determined by enzyme-linked immunosorbent assays (ELISA). Serum iron concentration was measured on Architect c8000 System. RESULTS: In this work, we demonstrated that prohepcidin concentrations were significantly higher in group 3 (Me = 292,2 ng/ ml) in comparison with group 1 (Me = 150.7 ng/ml; p < 0.000001) or group 2 (Me = 118.1 ng/ml; p < 0.000001). We observed a positive correlation between age and prohepcidin concentration (R = 0.38; p = 0.001). The oldest group of volunteers also revealed significantly higher levels of ferritin and lower levels of serum iron in comparison with two groups of younger adults. Females showed significantly higher level of prohepcidin (Me = 226.51 ng/ml) than males (Me = 142.6 ng/ml; p = 0.01). We observed that females under 50 years of age had significantly higher levels of prohepcidin (Me = 290.9 ng/ml) in comparison with younger females (Me = 150.7 ng/ml; p = 0.0001), similar correlation was noticed in males (212.3 ng/ml vs 128.3 ng/ml; p = 0.007). CONCLUSIONS: Prohepcidin concentration increased significantly with age and was significantly higher in women than men. The results of our study show that serum prohepcidin concentration is age and sex dependent.

Physical Training Increases Erythroferrone Levels in Men.

Intense physical activity contributes to an increased demand for red blood cells, which transport oxygen to working muscles. The purpose of this study was to assess the concentration of erythroferrone (ERFE), the novel marker of erythroid activity in athletes, during the beginning of their training season. The study group consisted of 39 athletes aged 23.24 ± 3.77 years. The study was carried out during the athletes' preparatory period of the training cycle. The control group consisted of 34 healthy men aged 22.33 ± 2.77 years. The erythropoietic activity was evaluated by determining athletes' concentrations of erythropoietin (EPO) and erythroferrone (ERFE). The level of physical activity was assessed using the International Physical Activity Questionnaire (IPAQ). In the athletes' group, we observed higher concentrations of EPO (Me = 12.65 mIU/mL) and ERFE (40.00 pg/mL) compared to the control group (EPO: Me = 5.74 mIU/ml, p = 0.001; ERFE: Me = 25.50 pg/mL, p = 0.0034). The average intensity of physical exercise significantly differentiated the participants as far as EPO and ERFE concentrations. These results suggest that intense physical activity, at least at the beginning of the training season, may stimulate EPO production, which increases ERFE release. This seems to be an adaptative mechanism that provides adequate iron for enhanced erythropoiesis.

Hemostasis in Coronavirus Disease 2019-Lesson from Viscoelastic Methods: A Systematic Review.

Hemostatic unbalance is often observed in patients with coronavirus disease 2019 (COVID-19), and patients with severe disease are at high risk of developing thromboembolic complications. Viscoelastic methods (VEMs), including thrombelastography (TEG) and thromboelastometry (TEM), provide data on the nature of hemostatic disturbance. In this systematic review, we assessed the performance of TEG and TEM in the assessment of blood coagulation and fibrinolysis in patients with COVID-19. PubMed, Scopus, Web of Science Core Collection, medRxiv, and bioRxiv were systematically searched for clinical studies evaluating TEG and/or TEM variables in COVID-19 individuals. Ten studies, with a total of 389 COVID-19 patients, were included, and VEMs were performed in 292 of these patients. Most patients (90%) presented severe COVID-19 and required mechanical ventilation. TEG and TEM variables showed that these patients displayed hypercoagulability and fibrinolysis shutdown, despite the use of appropriate thromboprophylaxis. However, the mechanism underlying these phenomena and their clinical significance in COVID-19 patients who developed thrombosis are still not clear. Further studies are warranted if VEMs might help to identify those at highest risk of thrombotic events and who therefore may derive the greatest benefit from antithrombotic therapy.

Unbalance in Iron Metabolism in Childhood Leukemia Converges with Treatment Intensity: Biochemical and Clinical Analysis.

OBJECTIVE: The aim of this study was to evaluate non-transferrin-bound iron (NTBI) and labile plasma iron (LPI) levels and other parameters of iron metabolism in children undergoing therapy for acute leukemia or after hematopoietic cell transplantation (HCT), in the context of iron overload. PATIENTS: A total number of 85 children were prospectively included into four groups: controls, acute leukemia de novo, acute leukemia after intensive treatment, and after HCT. METHODS: The following iron metabolism parameters were analyzed: (1) parameters measuring functional and storage iron pools: NTBI, LPI, iron, transferrin, total iron-binding capacity, ferritin, ferritin heavy and light chains; (2) proteins regulating iron absorption and its release from tissue stores: hepcidin, soluble hemojuvelin, soluble ferroportin-1; (3) proteins regulating the erythropoietic activity of bone marrow: erythroferrone, erythropoietin, soluble transferrin receptor. RESULTS: Intensive treatment of leukemia in children was associated with the presence of serum NTBI and LPI, which was the highest in the HCT group followed by the acute leukemia after treatment and de novo groups. In patients after HCT, the most significant changes were found in NTBI, LPI, iron, ferritin, hepcidin, and ferroportin-1 levels. CONCLUSIONS: The occurrence of NTBI and LPI in the circulation and the intensification of disturbances in iron metabolism were associated with the intensity of the anti-leukemic treatment.