RESUMO
Abstract Hemochromatosis is currently characterized by the iron overload caused by hepcidin deficiency. Large advances in the knowledge on the hemochromatosis pathophysiology have occurred due to a better understanding of the protein of the iron metabolism, the genetic basis of hemochromatosis and of other iron overload diseases or conditions which can lead to this phenotype. In the present review, the main aims are to show updates on hemochromatosis and to report a practical set of therapeutic recommendations for the human factors engineering protein (HFE) hemochromatosis for the p.Cys282Tyr (C282Y/C282Y) homozygous genotype, elaborated by the Haemochromatosis International Taskforce.
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Humanos , Masculino , Feminino , Distúrbios do Metabolismo do Ferro , Hemocromatose/diagnóstico , Hemocromatose/terapia , Flebotomia , Sobrecarga de Ferro , Hepcidinas/deficiência , Proteína da HemocromatoseRESUMO
OBJECTIVE@#To detect serum hepcidin and erythroferrone levels in child-bearing women with iron deficiency anemia (IDA), and to investigate the association between them and iron status parameters.@*METHODS@#The study consisted of 65 child-bearing women (35 with iron deficiency anemia and 30 age-matched healthy women). The levels of serum iron were detected by using automated chemistry analyzer, the contents of serum ferritin were detected by electrochemiluminescence immunoassay, and the levels of serum erythroferrone and hepcidin were detected by specific enzyme-linked immunosorbent assay (ELISA) kit. The quantitative variables between two groups were compared and analyzed by SPSS22.0 software. Spearman correlation was used to detect correlation between the parameters.@*RESULTS@#The levels of Hb, serum iron, ferritin and transferrin saturation were significantly decreased in IDA patients as compared with in control group (P0.05). In IDA patients, serum hepcidin concentrations were positively correlated with hemoglobin concentration, serum iron, serum ferritin and transferrin saturation (r=0.448, r=0.496, r=0.754, r=0.491). But, serum erythroferrone concentrations showed no correlation with hemoglobin concentration, serum iron, serum ferritin, transferrin saturation and hepcidin (P>0.05).@*CONCLUSION@#Serum hepcidin levels were significantly decreased in child-bearing women with IDA, but the serum erythroferrone levels were not obviously different between two groups, suggesting that serum erythroferrone may be not involved in the regulation of iron metabolism in child-bearing women with mild and moderate IDA.
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Criança , Feminino , Humanos , Anemia Ferropriva , Ensaio de Imunoadsorção Enzimática , Ferritinas , Hepcidinas , Ferro/metabolismoRESUMO
Alzheimer's disease(AD) patients in China have been surging, and the resultant medical burden and care demand have a huge impact on the development of individuals, families, and the society. The active component compound of Epimedii Folium, Astragali Radix, and Puerariae Lobatae Radix(YHG) can regulate the expression of iron metabolism-related proteins to inhibit brain iron overload and relieve hypofunction of central nervous system in AD patients. Hepcidin is an important target regulating iron metabolism. This study investigated the effect of YHG on the expression of a disintegrin and metalloprotease-17(ADAM17), a key enzyme in the hydrolysis of β amyloid precursor protein(APP) in HT22 cells, by mediating hepcidin. To be specific, HT22 cells were cultured in vitro, followed by liposome-mediated siRNA transfection to silence the expression of hepcidin. Real-time PCR and Western blot were performed to examine the silencing result and the effect of YHG on hepcidin in AD cell model. HT22 cells were randomized into 7 groups: control group, Aβ25-35 induction(Aβ) group, hepcidin-siRNA(siRNA) group, Aβ25-35 + hepcidin-siRNA(Aβ + siRNA) group, Aβ25-35+YHG(Aβ+YHG) group, hepcidin-siRNA+YHG(siRNA+YHG) group, Aβ25-35+hepcidin-siRNA+YHG(Aβ+siRNA+YHG) group. The expression of ADAM17 mRNA in cells was detected by real-time PCR, and the expression of ADAM17 protein by immunofluorescence and Western blot. Immunofluorescence showed that the ADAM17 protein expression was lower in the Aβ group, siRNA group, and Aβ+siRNA group than in the control group(P<0.05) and the expression was lower in the Aβ+siRNA group(P<0.05) and higher in the Aβ+YHG group(P<0.05) than in the Aβ group. Moreover, the ADAM17 protein expression was lower in the Aβ+siRNA group(P<0.05) and higher in the siRNA+YHG group(P< 0.05) than in the siRNA group. The expression was higher in the Aβ+siRNA+YHG group than in the Aβ+siRNA group(P<0.05). The results of Western blot and real-time PCR were consistent with those of immunofluorescence. The experiment showed that YHG induced hepcidin to up-regulate the expression of ADAM17 in AD cell model and promote the activation of non-starch metabolic pathways, which might be the internal mechanism of YHG in preventing and treating AD.
Assuntos
Humanos , Proteína ADAM17 , Doença de Alzheimer/genética , Peptídeos beta-Amiloides , Medicamentos de Ervas Chinesas/farmacologia , Hepcidinas/genética , PuerariaRESUMO
ABSTRACT Introduction: Glomerular hyperfiltration may lead to proteinuria and chronic kidney disease in unilateral multicystic dysplastic kidney (MCDK). We aimed to investigate the urine neutrophil-gelatinase-associated lipocalin (NGAL), netrin-1, hepcidin, and C-C motif chemokine ligand-2 (MCP-1/CCL-2) levels in patients with MCDK. Methods: Thirty-two patients and 25 controls were included. The urine hepcidin, netrin-1, NGAL, and MCP-1/CCL-2 levels were determined by ELISA. Results: The patients had higher serum creatinine (Cr) levels, urine albumin, and netrin-1/Cr ratio with lower GFR. There were positive correlations between urine protein/Cr, MCP-1/CCL-2/Cr, and netrin-1 with NGAL (r = 0.397, p = 0.031; r = 0.437, p = 0.041, r = 0.323, p = 0.042, respectively). Urine netrin-1/Cr was positively correlated with MCP-1/CCL-2/Cr (r = 0.356, p = 0.045). There were positive associations between the presence of proteinuria and netrin-1/Cr, MCP-1/CCL-2/Cr, and NGAL/Cr [Odds ratio (OR): 1.423, p = 0.037, OR: 1.553, p = 0.033, OR: 2.112, p = 0.027, respectively)]. ROC curve analysis showed that netrin-1/Cr, MCP-1/CCL-2/Cr, and NGAL/Cr had high predictive values for determining proteinuria p = 0.027, p = 0.041, p = 0.035, respectively). Urine hepcidin/Cr was negatively correlated with tubular phosphorus reabsorption and was positively correlated with urine NGAL/Cr (r = -0.418, p = 0.019; r = 0.682, p = 0.000; respectively). Conclusions: MCP-1/CCL-2 may play a role in the development of proteinuria in MCDK. Netrin-1 may be a protective factor against proteinuria-induced renal injury. Urine hepcidin/Cr may reflect proximal tubule damage in MCDK. Urine NGAL/Cr may be a predictor of tubule damage by proteinuria.
Resumo Introdução: A hiperfiltração glomerular pode causar proteinúria e doença renal crônica no rim displásico multicístico unilateral (RDM). Nosso objetivo foi investigar os níveis de lipocalina associada à gelatinase neutrofílica na urina (NGAL), netrina-1, hepcidina e quimiocina C-C com ligante-2 (MCP-1/CCL-2) em pacientes com RDM. Métodos: Trinta e dois pacientes e 25 controles foram incluídos. Os níveis urinários de hepcidina, netrin-1, NGAL e MCP-1/CCL-2 foram determinados por ELISA. Resultados: Os pacientes apresentaram níveis séricos mais elevados de creatinina (Cr), albumina na urina e relação netrina-1/Cr com menor TFG. Houve correlação positiva entre proteína na urina/Cr, MCP-1/CCL-2/Cr e netrina-1 com NGAL (r = 0,397, p = 0,031; r = 0,437, p = 0,041, r = 0,323, p = 0,042, respectivamente). A netrina-1/Cr na urina foi correlacionada positivamente com MCP-1/CCL-2/Cr (r = 0,356, p = 0,045). Houve associações positivas entre a presença de proteinúria e netrina-1/Cr, MCP-1/CCL-2/Cr e NGAL/Cr [Odds ratio (OR): 1,423, p = 0,037, OR: 1,553, p = 0,033, OR: 2,112, p = 0,027, respectivamente) ]. A análise da curva ROC mostrou que netrina-1/Cr, MCP-1/CCL-2/Cr e NGAL/Cr apresentaram altos valores preditivos para determinar a proteinúria p = 0,027, p = 0,041, p = 0,035, respectivamente). A hepcidina/Cr na urina foi correlacionada negativamente com a reabsorção tubular de fósforo e positivamente com a NGAL/Cr na urina (r = -0,418, p = 0,019; r = 0,682, p = 0,000; respectivamente). Conclusões: MCP-1/CCL-2 pode ter participação no desenvolvimento de proteinúria no RDM. A Netrina-1 pode ser um fator protetor contra lesão renal induzida por proteinúria. Hepcidina/Cr na urina pode refletir danos em túbulos proximais no RDM. O valor de NGAL/Cr urinário pode ser um preditor de danos nos túbulos por proteinúria.
Assuntos
Humanos , Feminino , Rim Displásico Multicístico/metabolismo , Biomarcadores , Proteínas Proto-Oncogênicas , Quimiocinas , Creatinina , Hepcidinas , Lipocalina-2 , Netrina-1 , LigantesRESUMO
SUMMARY BACKGROUND Hepcidin is an important regulator of iron homeostasis. OBJECTIVES This cross-sectional study was conducted to evaluate the association between hepcidin and components of metabolic syndrome in patients with chronic kidney disease (CKD). DESIGN AND SETTING 103 CKD patients and 59 healthy volunteers were included in the study from the University Hospital. METHODS Serum hepcidin levels were measured by enyzme-linked immunosorbent assay (ELISA) test. As for the study parameters, age, sex, body mass index, renal diseases, serum biochemistry, complete blood count, iron and total iron-binding capacity, ferritin, high-sensitive C-reactive protein (hsCRP), C- reactive protein (CRP), and erythrocyte sedimentation rate (ESR) were evaluated. RESULTS The mean age of the patients was 58.63 ± 11.8 years. Hepcidin level was significantly associated with hypertension and higher uric acid levels (P < 0.05). There was a positive correlation between hepcidin and urea, uric acid, creatinine, ferritin, CRP, ESR, phosphorus, triglyceride, low-density lipoprotein (LDL), proteinuria and albuminuria in 24-hour urine collection. A negative correlation was found between hepcidin and estimated glomerular filtration rate (eGFR), hemoglobin, hematocrit, calcium, 25 OH vitamin D, pH, and bicarbonate levels. CONCLUSION Hepcidin, a well-known hormone regulator of iron metabolism, may play an important role in the pathogenesis of metabolic syndrome in patients with CKD, and further studies might delineate in-depth its potential as a promising early marker in these patients.
RESUMO FUNDAMENTO A hepcidina é um importante regulador da homeostase do ferro. OBJETIVOS Este estudo transversal foi realizado para avaliar a associação entre hepcidina e componentes da síndrome metabólica em pacientes com doença renal crônica (DRC). PROJETO E LOCAL Cento e três pacientes com DRC e 59 voluntários saudáveis foram incluídos no estudo no Hospital Universitário. MÉTODOS Os níveis séricos de hepcidina foram medidos pelo teste imunoenzimático (Elisa). Quanto aos parâmetros do estudo, idade, sexo, índice de massa corporal, doenças renais, bioquímica sérica, hemograma completo, capacidade de ligação total de ferro e ferro, ferritina, proteína C reativa altamente sensível (hsCRP), proteína C reativa (PCR) e taxa de sedimentação de eritrócitos (VHS) foram avaliados. RESULTADOS A idade média dos pacientes foi de 58,63±11,8 anos. Número de pacientes em cada estágio da DRC, do estágio I ao estágio V (não em terapia renal substitutiva). O nível de hepcidina foi significativamente associado à hipertensão e níveis mais altos de ácido úrico (P <0,05). Houve correlação positiva entre hepcidina e ureia, ácido úrico, creatinina, ferritina, PCR, VHS, fósforo, triglicerídeo, lipoproteína de baixa densidade (LDL), proteinúria e albuminúria na coleta de urina de 24 horas. Foi encontrada correlação negativa entre hepcidina e taxa de filtração glomerular estimada (TFGe), hemoglobina, hematócrito, cálcio, 25 OH de vitamina D, pH e níveis de bicarbonato. CONCLUSÃO A hepcidina é um hormônio bem conhecido que regula o metabolismo do ferro, mas também pode ser um importante contribuinte para os componentes da síndrome metabólica em pacientes com DRC.
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Humanos , Síndrome Metabólica , Estudos Transversais , Insuficiência Renal Crônica , Hepcidinas , Taxa de Filtração Glomerular , Pessoa de Meia-IdadeRESUMO
No abstract available.
Assuntos
Injúria Renal Aguda , Hepcidinas , Inflamação , Ferro , Lipocalinas , Metabolismo , NeutrófilosRESUMO
OBJECTIVE@#To explore the possible etiological factors of iron overload through detecting plasma hepcidin level of adult males at Tibet plateau.@*METHODS@#81 Tibetan male adult patients hospitalized in our department during January 2017 - December 2018 were selected, and divided into iron overload group and non-iron overload group. The difference in serum ferritin, serum iron, total iron binding capacity, hemoglobin, HBSAg, ALT, AST, albumin, creatinine and hepcidin of patients in each group were tested. To analyze the differences between groups. The regression analysis was applied to analyze the relationship between laboratory index and hepcidin.@*RESULTS@#The plasma hepcidin of iron overload group was significantly higher than that of the non-iron overload group [93.69 (65.57-133.92) ng/ml vs 63.93 (40.01-90.65) ng/ml] (P=0.005). And there was a positive correlation between plasma hepcidin and ferritin (β=0.03 ng/ml,95%CI 0.01-0.05) (P<0.01) and BMI (β=5.71 ng/ml,95%CI 0.54-10.88) (P<0.05).@*CONCLUSION@#Iron overload at Tibet plateau can not be attributed to hepcidin deficiency in Tibetan adult male patients. Iron metabolism disorders in Tibetan population may be associated with metabolic syndrome.
Assuntos
Adulto , Humanos , Masculino , Ferritinas , Hepcidinas , Ferro , Sobrecarga de Ferro , TibetRESUMO
Assuntos
Feminino , Humanos , Anemia , Comorbidade , Hepcidinas , Inflamação , Modelos Logísticos , Metabolismo , Mineradores , Estudos Prospectivos , Insuficiência Renal Crônica , TransferrinaRESUMO
ABSTRACT Background: Recently, a small peptide called Hepcidin, was found to have an important role in regulating the iron metabolism in anemia of chronic disease (ACD) patients. Hepcidin is regulated by a variety of conditions at the transcriptional level. Therefore, our study aims to predict the level of hepcidin serum using inflammation markers and iron indicators in patients afflicted with ACD and observe how this severity of inflammation separated the level of interleukin-6 (IL-6), as well the as hepcidin level. Methods: A cross-sectional data analysis was conducted on 80 ACD adult patients treated at the Sanglah Teaching Hospital in Bali, Indonesia. We used hepcidin serum and several markers, such as the hemoglobin level, inflammation markers, renal function tests, IL-6, and iron indicators, to predict the hepcidin level. Results: This study recruited 80 ACD patients, comprising 45 men (56.3%) and 35 women (43.7%). The mean age of the participants was 43 ± 16.5 years. Only IL-6, ferritin and serum creatinine correlate significantly with serum hepcidin from seven variables that were previously eligible to enter the analysis. This study found the model to predict the hepcidin level using IL-6 ferritin and the creatinine level as the hepcidin level (predicted) = −23.76 + 0.396 (IL 6) + 0.448 (ferritin) + 0.310 (creatinine). Conclusion: This study has revealed that the creatinine level, ferritin and IL-6 can be used to predict the hepcidin level in patients with anemia of chronic disease. It is to be hoped that further cohort studies can validate our formula to predict the hepcidin level.
Assuntos
Humanos , Masculino , Feminino , Adulto , Adulto , Hepcidinas , Indonésia , AnemiaRESUMO
OBJECTIVE@#This study was designed to evaluate hematological disorders and the orchestrating roles of hepcidin and IL-6 in rat models of thioacetamide (TAA) and carbon tetrachloride (CCl4) hepatotoxicity.@*METHODS@#Rats were intraperitoneally injected with TAA (10 mg/100 g rat weight dissolved in isosaline) or CCl4 (100 μL/100 g rat weight diluted as 1:4 in corn oil) twice weekly for eight consecutive weeks to induce subchronic liver fibrosis. Blood and tissue samples were collected and analyzed.@*RESULTS@#CCl4 but not TAA significantly decreased the RBCs, Hb, PCV, and MCV values with minimal alterations in other erythrocytic indices. Both hepatotoxins showed leukocytosis, granulocytosis, and thrombocytopenia. By the end of the experiment, the erythropoietin level increased in the CCl4 model. The serum iron, UIBC, TIBC, transferrin saturation%, and serum transferrin concentration values significantly decreased, whereas that of ferritin increased in the CCl4 model. TAA increased the iron parameters toward iron overload. RT-PCR analysis revealed increased expression of hepatic hepcidin and IL-6 mRNAs in the CCl4 model and suppressed hepcidin expression without significant effect on IL-6 in the TAA model.@*CONCLUSION@#These data suggest differences driven by hepcidin and IL-6 expression between CCl4 and TAA liver fibrosis models and are of clinical importance for diagnosis and therapeutics of liver diseases.
Assuntos
Animais , Masculino , Ratos , Análise Química do Sangue , Tetracloreto de Carbono , Toxicidade , Hepcidinas , Farmacologia , Injeções Intraperitoneais , Interleucina-6 , Farmacologia , Ferro , Sangue , Metabolismo , Leucocitose , Terapêutica , Cirrose Hepática , Terapêutica , Tioacetamida , Toxicidade , Trombocitopenia , Terapêutica , Transferrina , MetabolismoRESUMO
OBJECTIVE: In this study, we aimed to evaluate the serum hepcidin levels in attention deficit hyperactivity disorder (ADHD) patients that were newly diagnosed with no history of psychotropic drugs. METHODS: A total of 70 ADHD patients and 69 healthy controls were enrolled in our study. During the diagnosis, the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime version were applied. The sociodemographic data form, Turgay DSM-IV-Based Child and Adolescent Behavior Disorders Screening and Rating Scale, and Conners’ Rating Scales-Revised: Long Form were used for the clinical evaluation. Serum hepcidin levels were measured and compared between the groups. RESULTS: No significant difference between the groups in terms of age (p=0.533) and gender (p=0.397) was determined. In addition, the groups did not differ significantly for the other sociodemographic variables recorded. Serum hepcidin levels were found to be significantly higher in the patients with ADHD than healthy controls (p=0.019). CONCLUSION: To the best of our knowledge, this study is the first to evaluate the total serum hepcidin levels in ADHD patients. Our study findings may suggest that high levels of hepcidin may cause iron dysregulation in ADHD patients. However, further studies are required to establish a definite conclusion.
Assuntos
Adolescente , Criança , Humanos , Comportamento do Adolescente , Agendamento de Consultas , Transtorno do Deficit de Atenção com Hiperatividade , Diagnóstico , Hepcidinas , Ferro , Programas de Rastreamento , Transtornos do Humor , Psicotrópicos , EsquizofreniaRESUMO
Hypoxia inducible factor (HIF)-stabilizers are being developed for the renal anemia treatment. This small molecules inhibit prolyl hydroxylase domain (PHD)-containing enzymes, causing HIF activation instead of degradation under the state of normoxia, finally increase production of intrinsic erythropoiesis. Current treatment guidelines suggest that renal anemia should be treated mainly with iron and erythropoiesis stimulating agents (ESAs). But there are several complications and concerns such as hypertension, ESA refractory anemia and increased cardiovascular mortality in using ESAs. Advantages of HIF stabilizers over ESAs are orally available, no dose-up requirement for inflammation. So far new HIF stabilizers showed efficacy and safety in renal anemia treatment. This new therapeutic agent may emerge as a standard treatment option for renal anmia treatment.
Assuntos
Humanos , Anemia , Anemia Refratária , Hipóxia , Eritropoese , Hematínicos , Hepcidinas , Hipertensão , Inflamação , Ferro , Mortalidade , Prolil Hidroxilases , Insuficiência Renal CrônicaRESUMO
Objective: To investigate the serum expression and influencing factors of hepcidinin patients with classical paroxysmal nocturnal hemoglobinuria (PNH) . Methods: Retrospective analysis of 36 classical PNH patients from 2016.3 to 2017.3. Serum hepcidin concentration was measured by ELISA method. The relationship between serum hepcidin concentration and erythropoiesis and iron homeostasis parameters was evaluated. Results: The median serum hepcidin level of 36 classical PNH patients was 32.03 (23.11, 118.48) μg/L, it was significantly lower than of 181.42 (106.80, 250.53) μg/L in 292 normal control subjects (z=-5.107, P<0.001) . The median serum hepcidin of 56.41 (44.60, 95.06) μg/L in PNH patients with normal ferritin was significantly lower than that in normal controls. The median serum hepcidin concentration 23.75 (21.77, 30.35) μg/L in iron deficiency PNH patients was lower than that in the normal ferritin PNH patients. However, the median serum hepcidin level of classical PNH with elevated ferritin patients 336.19 (304.19, 375.08) μg/L was significantly higher not only than that of normal ferritin and iron deficiency PNH ones, but also than that of normal control subjects. Regression analysis showed that serum ferritin, transferrin saturation and serum albumin level were independent influencing factors of serum hepcidin level in patients with classical PNH. Conclusion: The decreased serum hepcidin level in patients with classical PNH was mainly influenced by iron metabolism factors.
Assuntos
Humanos , Ensaio de Imunoadsorção Enzimática , Ferritinas , Hemoglobinúria Paroxística , Hepcidinas , Estudos RetrospectivosRESUMO
An increase in biochemical concentrations of non-transferrin bound iron (NTBI) within the patients with an increase in serum iron concentration was evaluated with the following objectives: (a) Iron overloading diseases/conditions with free radicle form of ‘iron containing’ reactive oxygen species (ROS) and its imbalance mediated mortality, and (b) Intervention with iron containing drugs in context to increased redox iron concentration and treatment induced mortality. Literature search was done within Pubmed and cochrane review articles. The Redox iron levels are increased during dys-erythropoiesis and among transfusion recipient population and are responsive to iron-chelation therapy. Near expiry ‘stored blood units’ show a significant rise in the ROS level. Iron mediated ROS damage may be estimated by the serum antioxidant level, and show reduction in toxicity with high antioxidant, low pro-oxidant levels. Iron drug therapy causes a significant increase in NTBI and labile iron levels. Hospitalized patients on iron therapy however show a lower mortality rate. Serum ferritin is a mortality indicator among the high-dose iron therapy and transfusion dependent population. The cumulative difference of pre-chelation to post chelation ROS iron level was 0.97 (0.62; 1.32; N=261) among the transfusion dependent subjects and 2.89 (1.81–3.98; N=130) in the post iron therapy ‘iron ROS’ group. In conclusion, iron mediated mortality may not be mediated by redox iron among multi-transfused and iron overloaded patients.
Assuntos
Humanos , Tratamento Farmacológico , Ferritinas , Hepcidinas , Sobrecarga de Ferro , Ferro , Mortalidade , Oxirredução , Espécies Reativas de OxigênioRESUMO
Abstract Serum hepcidin levels may increase in response to infection and inflammation. The present study investigated the effect of nonsurgical periodontal therapy (NSPT) on levels of serum hepcidin, inflammatory markers, and iron markers. An interventional study was conducted on 67 patients (age 30-65 years) without other diseases, except for chronic periodontitis (CP). Patients were allocated to either CP or control groups. The CP group received supragingival and subgingival scaling and root planing procedures, whereas the control group received supragingival scaling. Probing depth (PD), bleeding on probing, clinical attachment level (CAL), visible plaque index (VPI), serum hepcidin and interleukin-6 (IL-6) levels, high-sensitivity C-reactive protein (hs-CRP), hematological markers, and iron markers were measured at baseline and at 90 days after NSPT. The CP group had statistically significant lower mean values for mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) (p ≤ 0.05). The control group had statistically significant reductions in hemoglobin, hematocrit, MCV, and MCH (p ≤ 0.05). Serum hepcidin, IL-6, and erythrocyte sedimentation rate (ESR) levels were significantly decreased in both groups after NSPT. Periodontal markers were more markedly reduced in the CP group compared with the control group (p ≤ 0.05). These findings suggest that NSPT may reduce the serum levels of IL-6, hepcidin, and periodontal parameters.
Assuntos
Humanos , Masculino , Feminino , Adulto , Periodontite Crônica/sangue , Hepcidinas/sangue , Ferro/sangue , Valores de Referência , Fatores de Tempo , Proteína C-Reativa/análise , Biomarcadores/sangue , Estudos de Casos e Controles , Índice de Placa Dentária , Interleucina-6/sangue , Resultado do Tratamento , Aplainamento Radicular/métodos , Perda da Inserção Periodontal/patologia , Perda da Inserção Periodontal/sangue , Estatísticas não Paramétricas , Periodontite Crônica/patologia , Periodontite Crônica/terapia , Gengiva/patologia , Pessoa de Meia-IdadeRESUMO
Iron is critical for almost all living organisms because it serves as a cofactor for many proteins and enzymes necessary for oxygen and energy metabolism. Disruption of iron homeostasis is associated with a wide range of diseases. Thus mammals have developed sophisticated mechanisms to maintain optimal range of iron concentration. Iron regulation involves processes at the systemic and cellular levels. These processes are regulated by hepcidin and iron regulatory proteins. Hepcidin modulates systemic iron homeostasis with ability to impede cellular iron export via interaction with the iron export protein, ferroportin. Whereas, iron regulatory proteins control cellular iron homeostasis by translational regulation of proteins which involve iron metabolism. Recent advances in the study of iron metabolism have shown promising results that hepcidin-targeted strategies may help to improve the diagnosis and treatment of iron related diseases. Although these strategies are now under development, ongoing studies can help to elucidate its application possibilities.
Assuntos
Diagnóstico , Metabolismo Energético , Hepcidinas , Homeostase , Distúrbios do Metabolismo do Ferro , Ferro , Proteínas Reguladoras de Ferro , Mamíferos , Metabolismo , OxigênioRESUMO
OBJECTIVE@#To investigate the diagnostic value of Hepcidin as a sepsis biomarker in critically ill adults.@*METHODS@#An observational study was conducted. The patients with suspected or proven infection admitted to intensive care unit (ICU) of Zhoupu Hospital Affiliated to Shanghai University of Medicine and Health Sciences from March 2016 to November 2017 were enrolled. According to the third international consensus definitions for sepsis and septic shock (Sepsis-3), the patients were divided into non-sepsis group and sepsis group, and the septic patients were subdivided into general sepsis subgroup and septic shock subgroup according to the severity of disease. The differences in serum Hepcidin, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), procalcitonin (PCT), C-reactive protein (CRP), white blood cell (WBC), neutrophil granulocytes (NEUT) and lactic acid (Lac) within 1 hour after ICU admission between non-sepsis and sepsis groups and among the sepsis subgroups were compared. The acute physiology and chronic health evaluation II (APACHE II) within 24 hours after ICU admission and sequential organ failure score (SOFA) were recorded, and the mortality rate was followed up for 28 days. Receiver operation characteristic curve (ROC) was used to evaluate and compare the diagnostic value of Hepcidin and PCT, CRP, WBC for sepsis. Logistic regression model was used to estimate the association between Hepcidin and sepsis. Spearman correlation analysis was used to analyze the correlation between Hepcidin and other parameters of sepsis patients.@*RESULTS@#A total of 183 patients were enrolled, 93 in the non-sepsis group and 90 in the sepsis group (48 with general sepsis and 42 with septic shock). (1) The levels of Hepcidin, IL-6, TNF-α, PCT, Lac in serum, and APACHE II and SOFA scores in the sepsis group were significantly higher than those in the non-sepsis group. ROC analysis showed that the area under the ROC curve (AUC) of Hepcidin and PCT for sepsis diagnosis were 0.865 [95% confidence interval (95%CI) = 0.807-0.911] and 0.848 (95%CI = 0.788-0.897), respectively, without statistical significance (Z = 0.443, P = 0.657). Furthermore, the AUC of Hepcidin for sepsis diagnosis was significantly higher than that of the conventional biomarkers CRP and WBC [AUC was 0.530 (95%CI = 0.455-0.604) and 0.527 (95%CI = 0.452-0.601), respectively] with statistical significance (both P < 0.01). When Hepcidin > 54.00 μg/L, its sensitivity for sepsis diagnosis was 95.56%, specificity was 66.67%, positive and negative predictive value was 73.51% and 93.94%, respectively. Parallel test was conducted for combination of Hepcidin and PCT, which showed that the AUC was 0.885, and the sensitivity and negative predictive value was significantly improved to 98.96% and 98.36%, respectively. Logistic regression analysis demonstrated that after adjusted for PCT, Hepcidin > 54.00 μg/L was also associated with sepsis independently, with odds ratio (OR) of 1.011 (95%CI = 1.008-1.015, P < 0.001), indicating that Hepcidin and PCT were not completely overlapped in the diagnosis of sepsis. (2) With the increase in infection severity, serum Hepcidin, PCT, IL-6, TNF-α, Lac, APACHE II, SOFA score and 28-day mortality all showed an increasing trend in patients. There was a significantly positive correlation between Hepcidin and IL-6, TNF-α, PCT, APACHE II, and SOFA in the sepsis patients (r value was 0.526, 0.449, 0.591, 0.359, and 0.374, respectively, all P < 0.01), but no correlation was found between Hepcidin and Lac (r = 1.104, P > 0.05).@*CONCLUSIONS@#Serum Hepcidin is a useful biomarker for the diagnosis of sepsis, and it is correlated to the severity of the sepsis. The combination of Hepcidin and PCT can improve the accuracy of diagnosis of sepsis.@*CLINICAL TRIAL REGISTRATION@#China Clinical Trial Registration Center, ChiCTR-DDD-16008522.
Assuntos
Adulto , Humanos , Biomarcadores , Proteína C-Reativa , Calcitonina , Peptídeo Relacionado com Gene de Calcitonina , China , Estado Terminal , Hepcidinas , Prognóstico , Precursores de Proteínas , Curva ROC , SepseRESUMO
Introduction: Metabolism of iron is altered in patients infected with chronically Hepatitis C. The aim of this study is to compare compare the hepcidin levels in between individuais chronically infected with HCV and uninfected individuals. The aim of this study is to compare the hepcidin serum levels between individuals chronically infected with HCV and uninfected individuals. Methods: A cross-sectional study evaluating hepcidin serum levels of mono-infected HCV (n=29), naive, non-diabetic, non-cirrhotic and non-obese patients by means of ELISA, compared to uninfected patients (n=9) with the same characteristics. The degree of liver fibrosis, according to the METAVIR scale on liver biopsies, the lipid profile, the resistance insulin level, as calculated on HOMA-IR (homeostatic model assessment for insulin resistance), the interleukin-6 (IL-6) and the ferritin serum levels were also measured. Results: The levels of hepcidin were significantly lower in HCV patients compared to controls (8.4 pg/mL (±4.94) vs. 19.51 pg/mL (±5.51)) with p<0.001. The levels of ferritin and hepcidin did not show any relation. There was no difference between hepcidin levels in relation to viral genotype, viral load, IL-6 and degrees of fibrosis within HCV infected individuals. Conclusion: It is possible that hepatic iron overload in this population is explained by suppressed levels of hepcidin in patients with HCV. (AU)
Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto , Pessoa de Meia-Idade , Interleucina-6/sangue , Hepatite C Crônica/complicações , Hepcidinas/sangue , Hepacivirus/efeitos dos fármacosRESUMO
En las últimas décadas se ha avanzado en el conocimiento de la regulación del metabolismo del Hierro (Fe). La Hepcidina (Hp), producida por los hepatocitos, regula la absorción de hierro desde el tubo digestivo y la liberación desde los depósitos del sistema macrofágico y del hígado. En caso de deficiencia de Fe, la Hp está disminuida entregando Fe a la transferrina (Tf). El aumento de Fe y de las citoquinas de la inflamación estimulan la producción de Hp. El ejecutor de la Hp es la Ferroportina (FP), único exportador de Fe. Hay reguladores naturales de la Hp, como la Matriptasa 2. Las mutaciones que limitan su expresión inducen dificultades en la disponibilidad de Fe (IRIDA, sobrecarga de Fe). En los últimos años se ha identificado la Eritroferrona, producida por los eritroblastos activos en la eritropoyesis. Inhibe la síntesis de Hp, permitiendo la liberación del hierro de los depósitos y su absorción por el tubo digestivo, para facilitar la disponibilidad de Fe para la eritropoyesis. Aún no está definido cómo se podrán utilizar estos elementos en el campo diagnóstico, su estandarización y su aplicación terapéutica, pero es probable que resulten de gran utilidad.
In the last decades, a lot of progress has been made on the knowledge of iron (Fe) metabolism regulation. Hepcidin (Hp) is produced by hepatocytes and it regulates the iron absorption from the duodenum and the liberation from macrophages and from the liver. When there is iron deficiency, Hp, which delivers iron to transferrin (Tf), is low. Iron overload and inflammation cytokines stimulate Hp production. The Hp natural executor is Ferroportin (FP), which is the only iron exporter from the cells. One of the natural regulators of Hp is Matriptasa 2, which down regulates Hp. Mutations that limit their expression induce iron overload and anemia (IRIDA). In the last few years, Erythroferrone (ERFE) was discovered. ERFE is produced by active erythroblasts: it inhibits Hp synthesis, allowing the iron liberation from deposits and its duodenal absorption, and also the iron release from macrophages facilitating the erythroid production. The erythroblastic activity, even ineffective, acts as a stimulus of ERFE synthesis. Until now, it has not been defined yethow these different variables could be used for diagnosis, its standardization, or for therapeutic applications, but it is highly probable that they will improve our knowledge and managements kills in this field.
Nas últimas décadas háavanços no conhecimento da regulação do metabolismo do Ferro (Fe). A Hepcidina (Hp), produzida pelos hepatócitos, regula a absorção do ferro desde o tubo digestivo e a liberação desde os depósitos do sistema macrofágico e do fígado. Em caso de deficiência de Fe, a Hp está diminuída entregando Fe à transferrina (Tf). O aumento de Fe e as citoquinas da inflamação estimulam a produção de Hp. O executor da Hp é a Ferroportina (Fp), único exportador de Fe. Há reguladores naturais da Hp, como a Matriptase 2. As mutações que limitam sua expressão induzem dificultades na disponibilidade de Fe (IRIDA, sobrecarga de Fe). Nos últimos anos se identificou que a Eritroferrona, produzida pelos eritroblastosativos na eritropoiese inibe a síntese de Hp, permitindo a liberação de ferro dos depósitos e a absorção pelo tubo digestivo, para facilitar a disponibilidade de Fe para a eritropoiese. Ain da não sedefiniu como poderãoser utilizadosestes elementos no campo diagnóstico, sua padronização e sua aplicação terapêutica, mas é provável que sejam de grande utilidade.