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1.
Sci Rep ; 11(1): 19618, 2021 10 04.
Artigo em Inglês | MEDLINE | ID: mdl-34608227

RESUMO

The pathophysiology and the factors determining disease severity in COVID-19 are not yet clear, with current data indicating a possible role of altered iron metabolism. Previous studies of iron parameters in COVID-19 are cross-sectional and have not studied catalytic iron, the biologically most active form of iron. The study was done to determine the role of catalytic iron in the adverse outcomes in COVID-19. We enrolled adult patients hospitalized with a clinical diagnosis of COVID-19 and measured serum iron, transferrin saturation, ferritin, hepcidin and serum catalytic iron daily. Primary outcome was a composite of in-hospital mortality, need for mechanical ventilation, and kidney replacement therapy. Associations between longitudinal iron parameter measurements and time-to-event outcomes were examined using a joint model. We enrolled 120 patients (70 males) with median age 50 years. The primary composite outcome was observed in 25 (20.8%) patients-mechanical ventilation was needed in 21 (17.5%) patients and in-hospital mortality occurred in 21 (17.5%) patients. Baseline levels of ferritin and hepcidin were significantly associated with the primary composite outcome. The joint model analysis showed that ferritin levels were significantly associated with primary composite outcome [HR (95% CI) = 2.63 (1.62, 4.24) after adjusting for age and gender]. Both ferritin and serum catalytic iron levels were positively associated with in-hospital mortality [HR (95% CI) = 3.22 (2.05, 5.07) and 1.73 (1.21, 2.47), respectively], after adjusting for age and gender. The study shows an association of ferritin and catalytic iron with adverse outcomes in COVID-19. This suggests new pathophysiologic pathways in this disease, also raising the possibility of considering iron chelation therapy.


Assuntos
COVID-19/patologia , Ferro/sangue , Adulto , Idoso , COVID-19/mortalidade , COVID-19/virologia , Estudos Transversais , Feminino , Ferritinas/sangue , Ferritinas/metabolismo , Hepcidinas/sangue , Hepcidinas/metabolismo , Mortalidade Hospitalar , Humanos , Ferro/química , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Respiração Artificial , SARS-CoV-2/isolamento & purificação , Índice de Gravidade de Doença , Transferrina/química , Transferrina/metabolismo
2.
Nutrients ; 13(8)2021 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-34444676

RESUMO

Iron deficiency with or without anemia, needing continuous iron supplementation, is very common in obese patients, particularly those requiring bariatric surgery. The aim of this study was to address the impact of weight loss on the rescue of iron balance in patients who underwent sleeve gastrectomy (SG), a procedure that preserves the duodenum, the main site of iron absorption. The cohort included 88 obese women; sampling of blood and duodenal biopsies of 35 patients were performed before and one year after SG. An analysis of the 35 patients consisted in evaluating iron homeostasis including hepcidin, markers of erythroid iron deficiency (soluble transferrin receptor (sTfR) and erythrocyte protoporphyrin (PPIX)), expression of duodenal iron transporters (DMT1 and ferroportin) and inflammatory markers. After surgery, sTfR and PPIX were decreased. Serum hepcidin levels were increased despite the significant reduction in inflammation. DMT1 abundance was negatively correlated with higher level of serum hepcidin. Ferroportin abundance was not modified. This study shed a new light in effective iron recovery pathways after SG involving suppression of inflammation, improvement of iron absorption, iron supply and efficiency of erythropoiesis, and finally beneficial control of iron homeostasis by hepcidin. Thus, recommendations for iron supplementation of patients after SG should take into account these new parameters of iron status assessment.


Assuntos
Gastrectomia/efeitos adversos , Hepcidinas/sangue , Ferro/deficiência , Adulto , Proteínas de Transporte de Cátions/análise , Estudos de Coortes , Suplementos Nutricionais , Duodeno/química , Duodeno/metabolismo , Eritrócitos/química , Feminino , Humanos , Absorção Intestinal/fisiologia , Ferro/administração & dosagem , Pessoa de Meia-Idade , Obesidade/sangue , Obesidade/complicações , Obesidade/cirurgia , Estudos Prospectivos , Protoporfirinas/sangue , Receptores da Transferrina/sangue , Fatores de Transcrição/análise
3.
Am J Hematol ; 96(10): 1275-1286, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34310730

RESUMO

Hematopoietic cell transplantation (HCT) brings important alterations in erythropoiesis and iron metabolism. Hepcidin, which regulates iron metabolism, increases in iron overload or inflammation and decreases with iron deficiency or activated erythropoiesis. Erythroferrone (ERFE) is the erythroid regulator of hepcidin. We investigated erythropoiesis and iron metabolism after allogeneic HCT in 70 patients randomized between erythropoietin (EPO) treatment or no EPO, by serially measuring hepcidin, ERFE, CRP (inflammation), soluble transferrin receptor (sTfR, erythropoiesis), serum iron and transferrin saturation (Tsat; iron for erythropoiesis) and ferritin (iron stores). We identified biological and clinical factors associated with serum hepcidin and ERFE levels. Serum ERFE correlated overall with sTfR and reticulocytes and inversely with hepcidin. Erythroferrone paralleled sTfR levels, dropping during conditioning and recovering with engraftment. Inversely, hepcidin peaked after conditioning and decreased during engraftment. Erythroferrone and hepcidin were not significantly different with or without EPO. Multivariate analyses showed that the major determinant of ERFE was erythropoiesis (sTfR, reticulocytes or serum Epo). Pretransplant hepcidin was associated with previous RBC transfusions and ferritin. After transplantation, the major determinants of hepcidin were iron status (ferritin at all time points and Tsat at day 56) and erythropoiesis (sTfR or reticulocytes or ERFE), while the impact of inflammation was less clear and clinical parameters had no detectable influence. Hepcidin remained significantly higher in patients with high compared to low pretransplant ferritin. After allogeneic HCT with or without EPO therapy, significant alterations of hepcidin occur between pretransplant and day 180, in correlation with iron status and inversely with erythroid ERFE.


Assuntos
Eritropoese , Transplante de Células-Tronco Hematopoéticas , Hepcidinas/metabolismo , Ferro/metabolismo , Hormônios Peptídicos/metabolismo , Adulto , Idoso , Eritropoese/efeitos dos fármacos , Eritropoetina/uso terapêutico , Feminino , Hepcidinas/sangue , Humanos , Ferro/sangue , Masculino , Pessoa de Meia-Idade , Hormônios Peptídicos/sangue , Transplante Homólogo
4.
J Pediatr Hematol Oncol ; 43(5): 186-192, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-34157011

RESUMO

INTRODUCTION: To clarify mechanisms of ineffective erythropoiesis on iron metabolism, studies on erythroid factors that regulating hepcidin suppression have been carried out. The aim of the current study is to identify associations between erythropoiesis and iron homeostasis parameters in ß-thalassemias. MATERIALS AND METHODS: This study consisted of 83 subjects: 21 thalassemia major (TM), 20 thalassemia intermedia (TI), 20 thalassemia trait (TT), and 22 healthy subjects (HS). Erythroferrone (ERFE), hepcidin, growth differentiation factor-15 (GDF15), erythropoietin (EPO), and iron status parameters were measured. RESULTS: Our results showed that TM and TI patients had higher hepcidin than the TT and control groups. The hepcidin/ferritin in TM patients was significantly lower than the other groups. GDF15 in TM and TI patients was significantly higher than in the TT and control groups. Also, TI group had significantly higher ERFE concentration and EPO activity when compared with the TM, TT, and HS groups. EPO activity showed positive correlation with ERFE and GDF15 concentrations. We could not find any correlation between ERFE and hepcidin concentrations. CONCLUSIONS: ERFE may be one of the parameters used to demonstrate erythropoietic activity level in thalassemias. More detailed studies are needed to clarify the role of ERFE in iron metabolism in the patients with thalassemias.


Assuntos
Eritropoese , Ferro/sangue , Talassemia/sangue , Talassemia/terapia , Adolescente , Adulto , Transfusão de Sangue , Criança , Feminino , Fator 15 de Diferenciação de Crescimento/sangue , Hepcidinas/sangue , Humanos , Masculino , Hormônios Peptídicos/sangue , Adulto Jovem
5.
J Int Soc Sports Nutr ; 18(1): 44, 2021 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-34098993

RESUMO

BACKGROUND: Intensive physical exercise that competitive sports athletes participate in can negatively affect their pro-oxidative-antioxidant balance. Compounds with high antioxidant potential, such as those present in chokeberry (Aronia melanocarpa), can prevent these adverse changes. We here investigated the effect of antioxidant supplementation on oxidative stress balance in young footballers. METHODS: The study was designed as a double-blind randomized trial. Diet of a group of young football players (male; n = 20; mean age, 15.8 years-old) was supplemented with 200 ml of chokeberry juice per day, for 7 weeks. The players were randomly assigned to the experimental (supplemented, FP-S; n = 12) and control (placebo, FB-C; n = 8) groups. Before and after the supplementation period, the participants performed a beep test. Venous blood was sampled for serum analysis before, immediately after, 3 h, and 24 h after the beep test. Serum levels of thiobarbituric acid reactive products, 8-hydroxy-2'-deoxyguanosine, total antioxidant capacity, iron, hepcidin, ferritin, myoglobin, and albumin, and morphological blood parameters (red blood cells, (RBC), haemoglobin (HGB), haematocrit (HCT) mean corpuscular volume (MCV) mean corpuscular haemoglobin (MCH), mean corpuscular haemoglobin concentration (MCHC), and lactic acid) were determined. RESULTS: Chokeberry juice supplementation did not significantly affect the outcome of the beep test. The supplementation did not significantly affect any of the morphological, biochemical, or performance parameters analysed. CONCLUSIONS: Chokeberry juice supplementation did not affect the measured parameters in the studied population, which may indicate insufficient antioxidant capacity of the juice.


Assuntos
Antioxidantes/administração & dosagem , Suplementos Nutricionais , Estresse Oxidativo , Futebol/fisiologia , Adolescente , Biomarcadores/sangue , Índice de Massa Corporal , Método Duplo-Cego , Sucos de Frutas e Vegetais , Testes Hematológicos , Hepcidinas/sangue , Humanos , Ferro/sangue , Masculino , Photinia , Albumina Sérica/metabolismo
6.
Nutrients ; 13(5)2021 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-34063273

RESUMO

Excessive adiposity is associated with several metabolic perturbations including disturbances in iron homeostasis. Increased systemic inflammation in obesity stimulates expression of the iron regulatory hormone hepcidin, which can result in a maldistribution of bodily iron, which may be implicated in metabolic dysfunction. This study aimed to investigate the effect of adiposity and any associated inflammation on iron homeostasis and the potential implications of dysregulated iron metabolism on metabolic health. Analyses are based on a subsample from the cross-sectional Irish National Adult Nutrition Survey (2008-2010) (n = 1120). Ferritin status and risk of iron overload were determined based on established WHO ferritin ranges. Participants were classed as having a healthy % body fat or as having overfat or obesity based on age- and gender-specific % body fat ranges as determined by bioelectrical impedance. Biomarkers of iron status were examined in association with measures of body composition, serum adipocytokines and markers of metabolic health. Excessive % body fat was significantly associated with increased serum hepcidin and ferritin and an increased prevalence of severe risk of iron overload amongst males independent of dietary iron intake. Elevated serum ferritin displayed significant positive associations with serum triglycerides and markers of glucose metabolism, with an increased but non-significant presentation of metabolic risk factors amongst participants with overfat and obesity at severe risk of iron overload. Increased adiposity is associated with dysregulations in iron homeostasis, presenting as increased serum hepcidin, elevated serum ferritin and an increased risk of iron overload, with potential implications in impairments in metabolic health.


Assuntos
Sobrecarga de Ferro/epidemiologia , Sobrecarga de Ferro/etiologia , Obesidade/fisiopatologia , Adipocinas/sangue , Adiposidade/fisiologia , Adulto , Biomarcadores/análise , Glicemia/análise , Composição Corporal , Fatores de Risco Cardiometabólico , Estudos Transversais , Feminino , Ferritinas/sangue , Hepcidinas/sangue , Homeostase , Humanos , Inflamação , Irlanda/epidemiologia , Masculino , Pessoa de Meia-Idade , Inquéritos Nutricionais , Obesidade/complicações , Prevalência , Fatores Sexuais , Triglicerídeos/sangue
7.
Am J Physiol Regul Integr Comp Physiol ; 321(2): R152-R161, 2021 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-34160288

RESUMO

Current markers of iron deficiency (ID), such as ferritin and hemoglobin, have shortcomings, and hepcidin and erythroferrone (ERFE) could be of clinical relevance in relation to early assessment of ID. Here, we evaluate whether exposure to altitude-induced hypoxia (2,320 m) alone, or in combination with recombinant human erythropoietin (rHuEPO) treatment, affects hepcidin and ERFE levels before alterations in routine ID biomarkers and stress erythropoiesis manifest. Two interventions were completed, each comprising a 4-wk baseline, a 4-wk intervention at either sea level or altitude, and a 4-wk follow-up. Participants (n = 39) were randomly assigned to 20 IU·kg body wt-1 rHuEPO or placebo injections every second day for 3 wk during the two intervention periods. Venous blood was collected weekly. Altitude increased ERFE (P ≤ 0.001) with no changes in hepcidin or routine iron biomarkers, making ERFE of clinical relevance as an early marker of moderate hypoxia. rHuEPO treatment at sea level induced a similar pattern of changes in ERFE (P < 0.05) and hepcidin levels (P < 0.05), demonstrating the impact of accelerated erythropoiesis and not of other hypoxia-induced mechanisms. Compared with altitude alone, concurrent rHuEPO treatment and altitude exposure induced additive changes in hepcidin (P < 0.05) and ERFE (P ≤ 0.001) parallel with increases in hematocrit (P < 0.001), demonstrating a relevant range of both hepcidin and ERFE. A poor but significant correlation between hepcidin and ERFE was found (R2 = 0.13, P < 0.001). The findings demonstrate that hepcidin and ERFE are more rapid biomarkers of changes in iron demands than routine iron markers. Finally, ERFE and hepcidin may be sensitive markers in an antidoping context.


Assuntos
Doença da Altitude/sangue , Altitude , Epoetina alfa/administração & dosagem , Eritropoese/efeitos dos fármacos , Hematínicos/administração & dosagem , Hepcidinas/sangue , Ferro/sangue , Hormônios Peptídicos/sangue , Doença da Altitude/diagnóstico , Biomarcadores/sangue , Dinamarca , Método Duplo-Cego , Feminino , Homeostase , Humanos , Injeções Intravenosas , Masculino , Proteínas Recombinantes/administração & dosagem , Espanha , Fatores de Tempo
8.
Am J Physiol Gastrointest Liver Physiol ; 320(6): G1105-G1110, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-33949198

RESUMO

Phlebotomies are performed in hereditary hemochromatosis (HH) to maintain normal iron concentrations. Proton-pump inhibitors (PPIs) can reduce the number of phlebotomies in patients with HH. However, in patients without HH, the iron concentrations do not appear to be compromised when using PPIs. Therefore, we aim to explain the differences in iron absorption between patients with and without HH. In 10 p.cysteine282tyrosine (p.C282Y) homozygous HH patients with normalized iron stores and 10 healthy control subjects (HCs), the iron parameters and hepcidin concentrations were determined before ingestion of a pharmacological dose of 50 mg iron [ferric iron (Fe3+)] polymaltose and hourly for 4 h afterward. This was repeated after 7 days of treatment with pantoprazole 40 mg once daily. Serum iron concentrations and transferrin saturation percentages dropped significantly during PPI use in the patients with HH, whereas no changes were observed in the HCs. Hepcidin concentrations were lower in the patients with HH compared with the HCs both before and during PPI use. In both groups, hepcidin levels did not significantly decrease during the treatment. Seven-day PPI use significantly reduces iron absorption in patients with HH but not in HCs. Changes in hepcidin concentrations could not explain these different PPI effects on iron absorption probably due to a small sample size.NEW & NOTEWORTHY This study confirms that lowering gastric acidity by proton pump inhibitors results in a reduction in iron absorption in patients with hemochromatosis and not in healthy control subjects. The presupposition that a decrease in hepcidin concentration in healthy control subjects in response to lowering gastric acidity can explain the difference in iron absorption between these groups could not be confirmed probably because of a small sample size.


Assuntos
Ferritinas/sangue , Hemocromatose/sangue , Hepcidinas/sangue , Ferro/sangue , Adulto , Índice de Massa Corporal , Feminino , Hemocromatose/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Pantoprazol/uso terapêutico , Inibidores da Bomba de Prótons/uso terapêutico
9.
Biomed Res Int ; 2021: 5560319, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33954177

RESUMO

Background: Iron overload in severe ß-thalassemia is a serious complication that occurs during the course of the disease. Information about the iron status during initial illness with ß-thalassemia major seemed to be limited. This study is aimed at analyzing iron status, serum hepcidin, and growth differentiation factor 15 (GDF15) levels in newly diagnosed ß-thalassemia major. Methods: A case-control study was performed at Dr. Hasan Sadikin General Hospital, which included 41 children with newly diagnosed ß-thalassemia major. Age- and sex-matched controls were enrolled. The subjects had no blood transfusion, had normal liver function, and had no sign of inflammation. The groups were compared in terms of the levels of hemoglobin (Hb), serum ferritin (SF), transferrin saturation (TS), serum hepcidin, and GDF15 as iron homeostasis parameters. Results: Of the 41 newly diagnosed ß-thalassemia major patients, those who were less than 24 months old had significantly lower median Hb levels than controls (5.0 vs. 11.7 g/dL, P < 0.001). The median SF and TS levels were significantly higher than those in controls (315.0 vs. 29.0 ng/mL, P < 0.001; 70.6 vs. 16.5%, P < 0.001), and median hepcidin was at the normal limit, but the value was higher in patients (251.0 vs. 123.1 ng/mL, P < 0.001). The median GDF15 level was significantly higher in patients (2,095.3 vs. 342.4 pg/mL, P < 0.001). There was a positive correlation between SF-TS, SF-hepcidin, TS-hepcidin, SF-GDF15, TS-GDF15, and hepcidin-GDF15 (P < 0.001). Conclusion: In newly diagnosed ß-thalassemia major, an increase in iron status occurred. This may be caused by increased iron absorption due to massive erythropoietic activity, characterized by an increase in GDF15 levels, which does not cause hepcidin suppression. The iron homeostasis response seems to be physiologically indicated by a tendency to increase hepcidin levels.


Assuntos
Eritropoese/fisiologia , Ferro/sangue , Talassemia beta , Estudos de Casos e Controles , Pré-Escolar , Feminino , Ferritinas/sangue , Fator 15 de Diferenciação de Crescimento/sangue , Hepcidinas/sangue , Humanos , Lactente , Recém-Nascido , Ferro/metabolismo , Masculino , Transferrina/análise , Talassemia beta/sangue , Talassemia beta/diagnóstico , Talassemia beta/epidemiologia
10.
Clin Nephrol ; 95(6): 303-311, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33835014

RESUMO

PURPOSE: Acute kidney injury (AKI) is a common complication of sepsis and has high mortality. The 2017 Acute Disease Quality Initiative (AQDI) workgroup proposed new definitions for AKI - transient AKI and persistent AKI; however, very little is known about the effect of transient and persistent septic AKI on short-term mortality among critically ill patients with sepsis. The purpose of this study was to assess the impact of persistent AKI on mortality and to evaluate whether serum hepcidin can predict the occurrence of persistent AKI in critically ill patients with sepsis. MATERIALS AND METHODS: This prospective observational study was performed in a general hospital mixed surgical-medical ICU in Pudong, China. Consecutive adults with sepsis admitted to the ICU with absence of chronic kidney disease, renal transplant, and AKI were included. AKI was defined according to the KDIGO criteria and classified as transient (< 48-hour duration) or persistent (48-hour duration). Blood samples were obtained within 6 hours from when AKI was diagnosed. RESULTS: A total of 90 patients with sepsis or septic shock were included in the analysis. 44 (48.89%) patients developed AKI during ICU stay: 20 (45.45%) had transient and 24 (54.55%) had persistent AKI. Persistent AKI has a higher mortality than transient AKI (66.7 vs. 30.0%, p = 0.002). Persistent AKI and sequential organ failure assessment (SOFA) scores were an independent predictor of 60-day mortality. Patients with persistent AKI had higher concentrations of serum creatinine (SCr) and hepcidin than transient AKI patients when AKI was diagnosed. Logistic regression indicated that serum hepcidin was an independent predictor of persistent AKI in septic patients, with a fairly predictive value (AUC 0.71, 95% CI: 0.47 - 0.87; p = 0.02). CONCLUSION: Persistent AKI was associated with increased 60-day mortality compared with transient AKI in septic patients. The serum hepcidin levels measured when AKI was diagnosed have a fair predictive value to predict the occurrence of persistent AKI in septic patients.


Assuntos
Injúria Renal Aguda/etiologia , Hepcidinas/sangue , Sepse/mortalidade , Injúria Renal Aguda/sangue , Idoso , Idoso de 80 Anos ou mais , Estado Terminal , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Sepse/sangue , Sepse/complicações
11.
Aging (Albany NY) ; 13(8): 11296-11314, 2021 04 04.
Artigo em Inglês | MEDLINE | ID: mdl-33820875

RESUMO

As a necessary trace element, iron is involved in many physiological processes. Clinical and basic studies have found that disturbances in iron metabolism, especially iron overload, might lead to bone loss and even be involved in postmenopausal osteoporosis. Hepcidin is a key regulator of iron homeostasis. However, the exact role of hepcidin in bone metabolism and the underlying mechanism remain unknown. In this study, we found that in postmenopausal osteoporosis cohort, the concentration of hepcidin in the serum was significantly reduced and positively correlated with bone mineral density. Ovariectomized (OVX) mice were then used to construct an osteoporosis model. Hepcidin overexpression in these mice significantly improved bone mass and rescued the phenotype of bone loss. Additionally, overexpression of hepcidin in OVX mice greatly reduced the number and differentiation of osteoclasts in vivo and in vitro. This study found that overexpression of hepcidin significantly inhibited ROS production, mitochondrial biogenesis, and PGC-1ß expression. These data showed that hepcidin protected osteoporosis by reducing iron levels in bone tissue, and in conjunction with PGC-1ß, reduced ROS production and the number of mitochondria, thus inhibiting osteoclast differentiation and bone absorption. Hepcidin could provide new targets for the clinical treatment of postmenopausal osteoporosis.


Assuntos
Hepcidinas/metabolismo , Proteínas Nucleares/metabolismo , Osteoporose Pós-Menopausa/patologia , Proteínas de Ligação a RNA/metabolismo , Fatores de Transcrição/metabolismo , Idoso , Animais , Densidade Óssea/genética , Diferenciação Celular/genética , Células Cultivadas , Estudos de Coortes , Modelos Animais de Doenças , Feminino , Regulação da Expressão Gênica , Hepcidinas/sangue , Hepcidinas/genética , Humanos , Ferro/metabolismo , Camundongos , Camundongos Transgênicos , Pessoa de Meia-Idade , Mitocôndrias/metabolismo , Biogênese de Organelas , Osteoclastos/citologia , Osteoclastos/patologia , Osteoporose Pós-Menopausa/sangue , Osteoporose Pós-Menopausa/diagnóstico , Pós-Menopausa/sangue , Pós-Menopausa/metabolismo , Cultura Primária de Células , Espécies Reativas de Oxigênio/metabolismo
12.
Blood Cells Mol Dis ; 89: 102569, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33930800

RESUMO

In current study, we discuss clinical oral iron refractoriness cases and highlight need for a classification system to define TMPRSS6 gene variants. Out of 231 cases of microcytic hypochromic anemia screened (Sept 2019-Dec 2020), 17 cases (7.35%) with unexplained iron refractoriness (URIDA) phenotype were enrolled after ruling out secondary causes and compliance related issues. 11 (65%) had absent/negligible response (0-0.4 g/dl Hb rise) while 6 (35%) partial (0.5-0.9 g/dl Hb rise) response to initial iron trial at 4-8 weeks. Of these 17 cases, inappropriate hepcidin levels (normal-high) were noted in 11/15 (73%) tested. TSAT/Hepcidin ratio was low in 13/15 (87%). Genetic analysis of TMPRSS6 gene by NGS revealed variations in 15/17 (88%) cases. 10/15 cases with variations harbored a common splice site INDEL that was noted to be pathogenic SNP (MAF-0.19) on case-control association study in combination with other known missense SNPs with an odds ratio of 6.38 and relative risk 2.66 (p- < 0.01).


Assuntos
Anemia Hipocrômica/tratamento farmacológico , Anemia Hipocrômica/genética , Ferro/uso terapêutico , Proteínas de Membrana/genética , Polimorfismo de Nucleotídeo Único , Serina Endopeptidases/genética , Administração Oral , Anemia Hipocrômica/sangue , Criança , Pré-Escolar , Feminino , Variação Genética , Hepcidinas/sangue , Humanos , Mutação INDEL , Lactente , Ferro/administração & dosagem , Masculino , Mutação de Sentido Incorreto
13.
Cell ; 184(4): 969-982.e13, 2021 02 18.
Artigo em Inglês | MEDLINE | ID: mdl-33571427

RESUMO

Iron overload causes progressive organ damage and is associated with arthritis, liver damage, and heart failure. Elevated iron levels are present in 1%-5% of individuals; however, iron overload is undermonitored and underdiagnosed. Genetic factors affecting iron homeostasis are emerging. Individuals with hereditary xerocytosis, a rare disorder with gain-of-function (GOF) mutations in mechanosensitive PIEZO1 ion channel, develop age-onset iron overload. We show that constitutive or macrophage expression of a GOF Piezo1 allele in mice disrupts levels of the iron regulator hepcidin and causes iron overload. We further show that PIEZO1 is a key regulator of macrophage phagocytic activity and subsequent erythrocyte turnover. Strikingly, we find that E756del, a mild GOF PIEZO1 allele present in one-third of individuals of African descent, is strongly associated with increased plasma iron. Our study links macrophage mechanotransduction to iron metabolism and identifies a genetic risk factor for increased iron levels in African Americans.


Assuntos
Canais Iônicos/metabolismo , Ferro/metabolismo , Afro-Americanos , Envelhecimento/metabolismo , Alelos , Animais , Estudos de Coortes , Contagem de Eritrócitos , Eritropoese , Mutação com Ganho de Função/genética , Hepatócitos/metabolismo , Hepcidinas/sangue , Hepcidinas/metabolismo , Humanos , Ferro/sangue , Sobrecarga de Ferro/metabolismo , Macrófagos/metabolismo , Mecanotransdução Celular , Camundongos Endogâmicos C57BL , Fagocitose , Fenótipo , Estresse Fisiológico
14.
Crit Care ; 25(1): 62, 2021 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-33588893

RESUMO

BACKGROUND: Anemia is a significant problem in patients on ICU. Its commonest cause, iron deficiency (ID), is difficult to diagnose in the context of inflammation. Hepcidin is a new marker of ID. We aimed to assess whether hepcidin levels would accurately guide treatment of ID in critically ill anemic patients after a prolonged ICU stay and affect the post-ICU outcomes. METHODS: In a controlled, single-blinded, multicenter study, anemic (WHO definition) critically ill patients with an ICU stay ≥ 5 days were randomized when discharge was expected to either intervention by hepcidin treatment protocol or control. In the intervention arm, patients were treated with intravenous iron (1 g of ferric carboxymaltose) when hepcidin was < 20 µg/l and with intravenous iron and erythropoietin for 20 ≤ hepcidin < 41 µg/l. Control patients were treated according to standard care (hepcidin quantification remained blinded). Primary endpoint was the number of days spent in hospital 90 days after ICU discharge (post-ICU LOS). Secondary endpoints were day 15 anemia, day 30 fatigue, day 90 mortality and 1-year survival. RESULTS: Of 405 randomized patients, 399 were analyzed (201 in intervention and 198 in control arm). A total of 220 patients (55%) had ID at discharge (i.e., a hepcidin < 41 µg/l). Primary endpoint was not different (medians (IQR) post-ICU LOS 33(13;90) vs. 33(11;90) days for intervention and control, respectively, median difference - 1(- 3;1) days, p = 0.78). D90 mortality was significantly lower in intervention arm (16(8%) vs 33(16.6%) deaths, absolute risk difference - 8.7 (- 15.1 to - 2.3)%, p = 0.008, OR 95% IC, 0.46, 0.22-0.94, p = 0.035), and one-year survival was improved (p = 0.04). CONCLUSION: Treatment of ID diagnosed according to hepcidin levels did not reduce the post-ICU LOS, but was associated with a significant reduction in D90 mortality and with improved 1-year survival in critically ill patients about to be discharged after a prolonged stay. TRIAL REGISTRATION: www.clinicaltrial.gov NCT02276690 (October 28, 2014; retrospectively registered).


Assuntos
Anemia Ferropriva/tratamento farmacológico , Hepcidinas/análise , Administração Intravenosa/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Anemia Ferropriva/complicações , Anemia Ferropriva/epidemiologia , Feminino , França/epidemiologia , Hepcidinas/sangue , Hospitais Universitários/organização & administração , Hospitais Universitários/estatística & dados numéricos , Humanos , Unidades de Terapia Intensiva/organização & administração , Unidades de Terapia Intensiva/estatística & dados numéricos , Ferro/análise , Ferro/sangue , Tempo de Internação/estatística & dados numéricos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde/métodos , Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricos , Método Simples-Cego , Fatores de Tempo
15.
Int J Lab Hematol ; 43 Suppl 1: 142-151, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33554466

RESUMO

INTRODUCTION: Studies have shown that iron metabolism is affected by coronavirus disease 19 (COVID-19), which has spread worldwide and has become a global health problem. Our study aimed to evaluate the relationship between COVID-19 and serum erythropoietin (EPO), hepcidin, and haptoglobin (Hpt) levels with disease severity, and other biochemical values. METHODS: Fifty nine COVID-19 patients hospitalized in the intensive care unit (ICU) and wards in our hospital between March and June 2020 and 19 healthy volunteers were included in the study. Participants were divided into mild, severe, and critical disease severity groups. Group mean values were analyzed with SPSS according to disease severity, mortality, and intubation status. RESULTS: Hemoglobin (Hb) levels were significantly lower in the critical patient group (P < .0001) and deceased group (P < .0001). The red blood cell distribution width-coefficient of variation (RDW-CV) and ferritin values were significantly higher in the intubated (P = .001, P = .005) and deceased (P = .014, P = .003) groups. Ferritin values were positively correlated with disease severity (P < .0001). Serum iron levels were lower in the patient group compared with the reference range. (P < .0001). It was found that the transferrin saturation (TfSat) was lower in the patient group compared with the control group (P < .0001). It was found that the mean EPO of the deceased was lower than the control group and the survived patient group (P = .035). Hepcidin levels were found to be significantly lower in the patient group (P < .0001). Hpt values were found to be significantly lower in the intubated group (P = .004) and the deceased group (P = .042). CONCLUSION: In our study, while serum iron and hepcidin levels decreased in patients diagnosed with COVID-19, we found that EPO and Hpt levels were significantly lower in critical and deceased patient groups. Our study is the first study examining EPO and Hpt levels in patients diagnosed with COVID-19.


Assuntos
COVID-19/sangue , Eritropoetina/sangue , Haptoglobinas/análise , Hepcidinas/sangue , SARS-CoV-2 , Idoso , Biomarcadores , Estudos Transversais , Feminino , Ferritinas/sangue , Hemoglobinas/análise , Homeostase , Humanos , Intubação Intratraqueal/estatística & dados numéricos , Ferro/sangue , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Transferrina/análise
16.
Medicine (Baltimore) ; 100(5): e24511, 2021 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-33592904

RESUMO

ABSTRACT: Pregnant women with excessive gestational weight gain express an inflammatory status with multiple negative effects on birth outcomes.The aim of this study was to identify the relationship between gestational weight gain at different gestational ages and inflammatory status in pregnant women and their newborns assessing both interleukin 6 and 8, as well as hepcidin in these couples.Our study included 170 pregnant women and their newborns. Pregnant women were clinically assessed at the end of the 1st trimester and at term, whereas the newborns were assessed over the first 3 days of life. The levels of interleukin 6, 8 and hepcidin were measured in both pregnant women and their newborns.We noticed higher levels of interleukin 6, interleukin 8 and hepcidin in pregnant women at the time of delivery as compared to the end of the 1st trimester. We observed a direct significant correlation between gestational weight gain at the time of delivery and interleukin 8 in both mothers [r = 0.1834, 95% CI: 0.0293-0.3290, (P = .0167)] and newborns [r = 0.1790, 95% CI: 0.0248-0.3249, (P = .0195)]. Our study underlined that a higher gestational weight gain resulted in a significantly higher birth weight [r = 0.2190, 95% CI: 0.0663-0.3617, (P = .0041)].Our findings suggest that interleukin 8 might be an important indicator of inflammatory status in both mothers and newborns. Moreover, excessive gestational weight gain was associated with an increase in birth weight.


Assuntos
Peso ao Nascer/fisiologia , Ganho de Peso na Gestação/fisiologia , Mediadores da Inflamação/sangue , Adulto , Índice de Massa Corporal , Feminino , Idade Gestacional , Hepcidinas/sangue , Humanos , Recém-Nascido , Interleucina-6/sangue , Interleucina-8/sangue , Lipídeos/sangue , Paridade , Gravidez , Resultado da Gravidez , Características de Residência , Fatores Socioeconômicos , Adulto Jovem
17.
Nutrients ; 13(2)2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33535496

RESUMO

Cancer is often accompanied by worsening of the patient's iron profile, and the resulting anemia could be a factor that negatively impacts antineoplastic treatment efficacy and patient survival. The first line of therapy is usually based on oral or intravenous iron supplementation; however, many patients remain anemic and do not respond. The key might lie in the pathogenesis of the anemia itself. Cancer-related anemia (CRA) is characterized by a decreased circulating serum iron concentration and transferrin saturation despite ample iron stores, pointing to a more complex problem related to iron homeostatic regulation and additional factors such as chronic inflammatory status. This review explores our current understanding of iron homeostasis in cancer, shedding light on the modulatory role of hepcidin in intestinal iron absorption, iron recycling, mobilization from liver deposits, and inducible regulators by infections and inflammation. The underlying relationship between CRA and systemic low-grade inflammation will be discussed, and an integrated multitarget approach based on nutrition and exercise to improve iron utilization by reducing low-grade inflammation, modulating the immune response, and supporting antioxidant mechanisms will also be proposed. Indeed, a Mediterranean-based diet, nutritional supplements and exercise are suggested as potential individualized strategies and as a complementary approach to conventional CRA therapy.


Assuntos
Anemia/complicações , Ferro/sangue , Estilo de Vida , Neoplasias/complicações , Anemia/sangue , Anemia Ferropriva/sangue , Animais , COVID-19 , Dieta , Alimentos Fortificados , Microbioma Gastrointestinal , Hepcidinas/sangue , Homeostase , Humanos , Inflamação/sangue , Fígado/metabolismo , Músculo Esquelético
19.
Arch. med. deporte ; 38(201): 22-27, ene.-feb. 2021. tab, graf
Artigo em Inglês | IBECS | ID: ibc-201640

RESUMO

Serum ferritin has been proposed as a predictor of hepcidin concentrations in response to exercise. However, this fact has not been studied in physically-active women. Therefore, the main objective of this study was to analyse the hepcidin response at different ferritin status before and after running exercise in physically active females. Fifteen eumenorrheic women performed a 40-min running protocol at 75% of VO2peak speed in different menstrual cycle phases (early-follicular phase, mid-follicular phase and luteal phase). Blood samples were collected pre-exercise, 0h post-exercise and 3h post-exercise. For statistics, participants were divided into two groups according to their pre-exercise ferritin levels (< 20 and ≥ 20 μg/L). Through menstrual cycle, hepcidin was lower in both early follicular phase (p = 0.024; 64.81 ± 22.48 ng/ml) and mid-follicular phase (p = 0.007; 64.68 ± 23.91 ng/ml) for < 20 μg/L ferritin group, in comparison with ≥20 μg/L group (81.17 ± 27.89 and 79.54 ± 22.72 ng/ml, respectively). Hepcidin showed no differences between both ferritin groups in either pre-exercise, 0h post-exercise and 3h post-exercise. Additionally, no association between pre-exercise ferritin and hepcidin levels 3 h post-exercise (r = -0.091; p = 0.554) was found. Menstrual cycle phase appears to influence hepcidin levels depending on ferritin reserves. In particular, physically-active females with depleted ferritin reserves seems to present lower hepcidin levels during the early-follicular phase and mid-follicular phase. However, no association between ferritin and hepcidin levels was found in this study. Hence, ferritin levels alone may not be a good predictor of hepcidin response to exercise in this population. Multiple factors such as sexual hormones, training loads and menstrual bleeding must be taken into account


La ferritina sérica parece ser un predictor de la respuesta de la hepcidina al ejercicio. Sin embargo, este hecho no ha sido estudiado en mujeres físicamente activas. El objetivo fue analizar la respuesta de la hepcidina en diferentes estados de la ferritina antes y después del ejercicio. Quince mujeres eumenorreicas realizaron un protocolo de carrera de 40 minutos al 75% de la velocidad VO2pico en diferentes fases del ciclo menstrual (fase folicular temprana, fase folicular media y fase lútea). Se recogieron muestras de sangre antes del ejercicio y a las 0h y 3h después del ejercicio. Las participantes se dividieron en dos grupos según sus niveles de ferritina previos al ejercicio (< 20 y ≥ 20 μg/L). La hepcidina fue más baja tanto en la fase folicular temprana (p = 0,024; 64,81 ± 22,48 ng/ml) como en las fase folicular media (p = 0,007; 64,68 ± 23,91 ng/ml) para el grupo de ferritina < 20 μg/L en comparación con el grupo de ferritina ≥ 20 μg/L (81,17 ± 27,89 y 79,54 ± 22,72 ng/ml, respectivamen-te). La hepcidina no mostró diferencias entre ambos grupos de ferritina para ninguno de los momentos (antes del ejercicio ejercicio, 0h y 3h después del ejercicio). No se encontró ninguna asociación entre los niveles de ferritina previos al ejercicio y los niveles de hepcidina 3h posteriores al ejercicio (r = -0,091; p = 0,554). El ciclo menstrual parece influir en los niveles de hepcidina dependiendo de las reservas de ferritina. En particular, las mujeres físicamente activas con reservas de ferritina agotadas parecen presentar niveles de hepcidina más bajos durante la fase folicular temprana y la fase folicular media. Sin embargo, no se encontró ninguna asociación entre la ferritina y la hepcidina. Por lo tanto, los niveles de ferritina por sí solos pueden no ser un buen predictor de la respuesta de la hepcidina al ejercicio en esta población. Se deben tener en cuenta múltiples factores como las hormonas sexuales, las cargas de entrenamiento y el sangrado menstrual


Assuntos
Humanos , Feminino , Adulto , Treinamento de Força , Corrida/fisiologia , Ferritinas/sangue , Hepcidinas/sangue , Ciclo Menstrual/sangue , Consumo de Oxigênio/fisiologia , Índice de Massa Corporal , Valores de Referência , Fatores de Tempo , Estradiol/sangue , Progesterona/sangue
20.
Nutrients ; 13(1)2021 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-33466578

RESUMO

Limited evidence suggests that serum iron and hepcidin concentrations are dysregulated in obesity and inflammation. The objective of the present study was to compare C-reactive protein, interleukin-6, circulating levels of hepcidin, serum lipids, and iron status in obese vs. normal-weight women of childbearing age. Healthy women aged 18-30 years were recruited for the study (n = 47: 25 obese and 22 normal weight). Fasting blood samples were obtained to measure serum lipids (total cholesterol, HDL, LDL cholesterol, triglycerides, non-HDL cholesterol), complete blood count, serum iron, total iron-binding capacity, transferrin saturation, serum ferritin, hepcidin, C-reactive protein, and interleukin-6. Obese women had significantly higher mean serum C-reactive protein (p < 0.001), interleukin-6 (p < 0.001), hepcidin (p = 0.024), triglycerides (p < 0.001) and total cholesterol/HDL ratio (p < 0.001) but lower HDL (p = 0.001) and serum iron/hepcidin ratio (p = 0.011) compared with normal-weight women. BMI correlated positively with inflammatory markers, triglycerides, LDL and total cholesterol/HDL ratio, and negatively with HDL and serum iron/hepcidin ratio. Serum iron correlated negatively with ferritin in the obese group (p = 0.030) but positively in normal weight women (p = 0.002). BMI and ferritin were the only predictors of serum iron/hepcidin ratio accounting for 23% of the variation among subjects. Studies are needed to examine anti-inflammatory dietary approaches that can improve iron biomarkers in obese women.


Assuntos
Hepcidinas/sangue , Ferro/sangue , Obesidade/sangue , Obesidade/epidemiologia , Adolescente , Adulto , Biomarcadores/sangue , Índice de Massa Corporal , Estudos Transversais , Feminino , Ferritinas/sangue , Humanos , Inflamação , Adulto Jovem
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