RESUMO
Males of the olive fruit fly Bactrocera oleae vibrate and stridulate their wings at dusk producing sounds different from flight sounds with no confirmed behavior role. We recorded and performed a temporal-spectral analysis of this sound. Sound produced by male wing vibration/stridulation consists of intermittent pulses of highly variable duration and of fundamental frequency of around 350 Hz. Flight sound has a much lower fundamental frequency of approximately 180 Hz. Males begin to display wing vibration and sound production at the beginning of their sexual maturity at the 5th day of their age. This behavior is more pronounced in the presence of another conspecific male and observed less in male-female pairs or in solitary males. Broadcasts of the recorded sound did not attract flies of either sex. The highest fundamental frequency was found in association with wing vibrations emitted by male-male pairs, followed by those emitted by male-female pairs and then solitary males, which showed the lowest frequency values. The mean pulse duration and interpulse interval were shorter in male-male pairs than in male-female pairs. We assume that the male wing vibration and the produced signal, apart from its possible role in the courtship of the females, could also be associated with male-male interactions for territorial and rival activities, for which further experiments are required.
Assuntos
Comportamento Sexual Animal , Tephritidae , Acústica , Animais , Drosophila , Feminino , Masculino , Som , Asas de AnimaisRESUMO
BACKGROUND: We describe our experience from a multi-national application of a European Union-funded research-driven paediatric trial (DEEP-2, EudraCT 2012-000353-31; NCT01825512). This paper aims to evaluate the impact of the local and national rules on the trial authorisation process in European and non-European countries. National/local provisions and procedures, number of Ethics Committees and Competent Authorities to be addressed, documentation required, special provisions for the paediatric population, timelines for completing the authorisation process and queries received were collected; compliance with the European provisions were evaluated. Descriptive analysis, Wilcoxon Rank-Sum test and General Linear Model analysis were used to determine factors potentially influencing the timelines. The Cluster Analysis procedure was used to identify homogenous groups of cases. RESULT: The authorisation process was completed in 7.7 to 53.8 months in European countries and in 17.1 to 27.1 months in non-European countries. The main factors influencing these timelines were the requests for changes/clarifications in European countries and the different national legislations in non-European countries. CONCLUSION: This work confirms that the procedures and requirements for the clinical trial application of a paediatric trial are different. In the European Union, the timeframes for submission were generally harmonised but longer. In non-European countries, delays were caused by national dispositions but the entire authorisation process resulted faster with less requests from ECs/CAs. The upcoming application of Regulation (EU) 536/2014 is expected to harmonise practices in Europe and possibly outside. Networks on paediatric research acting at international level will be crucial in this effort.
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Princípios Morais , Pesquisadores , Criança , Europa (Continente) , União Europeia , HumanosRESUMO
Objective: To develop and evaluate a software application capable of conducting Pure-Tone Audiometry tests in clinical practice. Design: We designed and developed a mobile software application for iPad devices that performs Pure-Tone Audiometry according to ANSI and IEC standards. The application is proposed to be operated by a trained audiologist inside a sound booth. No extra equipment is required. Hence, it updates the procedure by showing the versatility of the proposed system. Particularly, it provides manual and automated measurement, including air- and bone-conduction audiometry. Study sample: Twenty-nine participants-patients of Papageorgiou Hospital, Thessaloniki, Greece were tested, with all degrees of hearing sensitivity. Manual air- and bone-conduction Pure-Tone Audiometry was conducted inside a sound booth. Participants were tested with conventional audiometry and the audiometric application, in order to validate the tablet-based audiometer for measuring hearing thresholds. Results: The majority (90.9%) of air-conduction estimated hearing thresholds and (90.8%) of air-bone gaps were within 5 dB, compared to results obtained by conventional audiometry. Thus, threshold differences were not significant. Conclusions: The proposed audiometer is a reliable and valid tool for hearing assessment. Owing to certain limitations, mobile devices can provide a feasible substitute for conventional audiometry in clinical practice.
Assuntos
Audiometria de Tons Puros/instrumentação , Computadores de Mão , Transtornos da Audição/diagnóstico , Audição , Aplicativos Móveis , Design de Software , Estimulação Acústica , Adolescente , Adulto , Idoso , Limiar Auditivo , Condução Óssea , Estudos de Casos e Controles , Feminino , Transtornos da Audição/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Índice de Gravidade de Doença , Adulto JovemRESUMO
Iron is an essential nutrient that is potentially toxic due to its redox reactivity. Insufficient iron supply to erythroid cells, the major iron consumers in the body, leads to various forms of anemia. On the other hand, iron overload (hemochromatosis) is associated with tissue damage and diseases of liver, pancreas, and heart. Physiological iron balance is tightly controlled at the cellular and systemic level by iron regulatory proteins (IRP1, IRP2) and the iron regulatory hormone hepcidin, respectively. Underlying mechanisms often intersect to achieve optimal iron utilization, to control immune responses, and to prevent iron toxicity. This review focuses on systemic iron homeostasis in the context of erythropoiesis, a highly iron-demanding process. We discuss the function and regulation of hepcidin by various stimuli, and highlight hepcidin-dependent and -independent mechanisms that link iron utilization with maturation of erythroid progenitor cells. © 2017 IUBMB Life, 69(6):399-413, 2017.
Assuntos
Anemia Ferropriva/genética , Células Precursoras Eritroides/metabolismo , Eritropoese/genética , Hemocromatose/genética , Homeostase/genética , Ferro/metabolismo , Anemia Ferropriva/metabolismo , Anemia Ferropriva/patologia , Proteínas de Transporte de Cátions/genética , Proteínas de Transporte de Cátions/metabolismo , Diferenciação Celular , Células Precursoras Eritroides/citologia , Regulação da Expressão Gênica , Hemocromatose/metabolismo , Hemocromatose/patologia , Hepcidinas/genética , Hepcidinas/metabolismo , Humanos , Proteína 1 Reguladora do Ferro/genética , Proteína 1 Reguladora do Ferro/metabolismo , Proteína 2 Reguladora do Ferro/genética , Proteína 2 Reguladora do Ferro/metabolismo , Transdução de SinaisRESUMO
Male-pattern baldness (MPB) is a common and highly heritable trait characterized by androgen-dependent, progressive hair loss from the scalp. Here, we carry out the largest GWAS meta-analysis of MPB to date, comprising 10,846 early-onset cases and 11,672 controls from eight independent cohorts. We identify 63 MPB-associated loci (P<5 × 10-8, METAL) of which 23 have not been reported previously. The 63 loci explain â¼39% of the phenotypic variance in MPB and highlight several plausible candidate genes (FGF5, IRF4, DKK2) and pathways (melatonin signalling, adipogenesis) that are likely to be implicated in the key-pathophysiological features of MPB and may represent promising targets for the development of novel therapeutic options. The data provide molecular evidence that rather than being an isolated trait, MPB shares a substantial biological basis with numerous other human phenotypes and may deserve evaluation as an early prognostic marker, for example, for prostate cancer, sudden cardiac arrest and neurodegenerative disorders.
Assuntos
Alopecia/genética , 3-Oxo-5-alfa-Esteroide 4-Desidrogenase/genética , Adipogenia/genética , Estudos de Casos e Controles , Fator 5 de Crescimento de Fibroblastos/genética , Estudos de Associação Genética , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/genética , Fatores Reguladores de Interferon/genética , Masculino , Melatonina , Proteínas de Membrana/genética , Fenótipo , Transdução de Sinais/genética , Transativadores/genéticaRESUMO
INTRODUCTION: This article aims to investigate the critical role of the venous-perforator in the decision-making process of choosing the best suitable perforator-complex in a deep inferior epigastric perforator (DIEP) flap. METHODS: Forty consecutive DIEP breast reconstructions were pre-operatively evaluated by CT-Angiography to identify the dominant and centrally located abdominal wall perforators. The CTA results were used as a guide to conduct a Color-Duplex-Ultrasound examination that was mainly focused on investigating the accompanying venous-perforator. In group-A (n = 20) perforator-complex selection was based on the size of the arterial-perforator, whilst in group-B (n = 20) it was based on the size of the venous-perforator. RESULTS: All single perforator-complex DIEP flaps survived. No significant differences were recorded concerning the size of arterial-perforator between the two groups; however the size of venous-perforator was significantly larger in group-B (P < 0.05). In group-A, four flaps showed vascular compromise intraoperative that was salvaged by flap supercharge with the superficial inferior epigastric system. In contrast, in group-B, all flaps were re-vascularized uneventfully (P < 0.05). Physical examination revealed a palpable mass in one patient and ultrasound investigation added three cases with a firm area of scar tissue in group-A, but no fat necrosis was detected in group-B (P < 0.05). CONCLUSIONS: The CTA-guided duplex ultrasonography could direct the perforator-complex selection according to the size of the venous-perforator, and may reduce the intraoperative problems and the incidence of fat necrosis.
Assuntos
Mamoplastia/métodos , Retalho Perfurante/irrigação sanguínea , Adulto , Angiografia/métodos , Feminino , Humanos , Microcirurgia/métodos , Pessoa de Meia-Idade , Estudos Prospectivos , Tomografia Computadorizada por Raios X , Ultrassonografia Doppler em Cores , Ultrassonografia Doppler Dupla , Ultrassonografia MamáriaRESUMO
Minerals play a key role in the regulation of metabolic and physiological pathways. Adequate intake is required to maintain homeostasis, cell protection, functionality, and health, while deficiencies are associated with specific illnesses. Among the minerals, calcium, copper, iron, selenium, and zinc are considered especially important because of their physiological roles and their participation in a variety of biological processes. Also, these elements are associated with genetic diseases and are known to interact with genetic variants in a wide range of diseases.
Assuntos
Minerais/administração & dosagem , Estudos de Casos e Controles , Doenças Genéticas Inatas/genética , Humanos , Polimorfismo de Nucleotídeo ÚnicoRESUMO
BACKGROUND: Iron is utilized by several proteins as cofactor for major biological processes. However, iron may also harm cells by catalyzing the generation of free radicals and promoting oxidative stress. Acquisition, transport, utilization and storage of iron are tightly controlled to meet physiological needs and prevent excessive accumulation of the metal within cells. Plasma transferrin has been known for years as a central player in iron metabolism, assigned to circulate iron in a soluble, non-toxic form and deliver it to the erythron and other tissues. Recent data uncovered an additional role of transferrin as an upstream regulator of hepcidin, a liver-derived peptide hormone that controls systemic iron traffic. SCOPE OF REVIEW: Here, we review basic features of iron metabolism, highlighting the function of transferrin in iron transport and cellular iron uptake. We further discuss the role of hepcidin as an orchestrator of systemic iron homeostasis, and the mechanisms underlying hepcidin regulation in response to various physiological cues. Emphasis is given on the role of transferrin on iron-dependent hepcidin regulation. MAJOR CONCLUSIONS: Transferrin exerts a crucial function in the maintenance of systemic iron homeostasis as component of a plasma iron sensing system that modulates hepcidin expression. GENERAL SIGNIFICANCE: Proper expression of transferrin and hepcidin are essential for health, and disruption of their regulatory circuits is associated with iron-related disorders. This article is part of a Special Issue entitled Transferrins: Molecular mechanisms of iron transport and disorders.
Assuntos
Peptídeos Catiônicos Antimicrobianos/metabolismo , Ferro/metabolismo , Receptores da Transferrina/metabolismo , Transferrina/metabolismo , Animais , Peptídeos Catiônicos Antimicrobianos/genética , Proteínas Morfogenéticas Ósseas/metabolismo , Eritropoese , Hepcidinas , Homeostase , Humanos , Transporte de Íons , Ferro/sangue , Camundongos , Estresse Oxidativo , Oxigênio/metabolismoRESUMO
UNLABELLED: Mutations of the HFE2 gene are linked to juvenile hemochromatosis, a severe hereditary iron overload disease caused by chronic hyperabsorption of dietary iron. HFE2 encodes hemojuvelin (Hjv), a membrane-associated bone morphogenetic protein (BMP) coreceptor that enhances expression of the liver-derived iron regulatory hormone hepcidin. Hjv is primarily expressed in skeletal muscles and at lower levels in the heart and the liver. Moreover, a soluble Hjv form circulates in plasma and is thought to act as a decoy receptor, attenuating BMP signaling to hepcidin. To better understand the regulatory function of Hjv, we generated mice with tissue-specific disruption of this protein in hepatocytes or in muscle cells. The hepatic ablation of Hjv resulted in iron overload, quantitatively comparable to that observed in ubiquitous Hjv-/- mice. Serum iron and ferritin levels, transferrin saturation, and liver iron content were significantly (P < 0.001) elevated in liver-specific Hjv-/- mice. Hepatic Hjv mRNA was undetectable, whereas hepcidin expression was markedly suppressed (12.6-fold; P < 0.001) and hepatic BMP6 mRNA up-regulated (2.4-fold; P < 0.01), as in ubiquitous Hjv-/- counterparts. By contrast, the muscle-specific disruption of Hjv was not associated with iron overload or altered hepcidin expression, suggesting that muscle Hjv mRNA is dispensable for iron metabolism. Our data do not support any significant iron-regulatory function of putative muscle-derived soluble Hjv in mice, at least under physiological conditions. CONCLUSION: The hemochromatotic phenotype of liver-specific Hjv-/- mice suggests that hepatic Hjv is necessary and sufficient to regulate hepcidin expression and control systemic iron homeostasis.
Assuntos
Hemocromatose/metabolismo , Ferro/metabolismo , Fígado/metabolismo , Proteínas de Membrana/metabolismo , Músculo Esquelético/metabolismo , Animais , Peptídeos Catiônicos Antimicrobianos/genética , Peptídeos Catiônicos Antimicrobianos/metabolismo , Feminino , Proteínas Ligadas por GPI , Hemocromatose/genética , Proteína da Hemocromatose , Hepcidinas , Homeostase/fisiologia , Integrases/genética , Masculino , Proteínas de Membrana/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Mutantes , Mutagênese , Especificidade de Órgãos/fisiologiaRESUMO
Free flap vascular pedicle avulsion represents an extremely rare complication in reconstructive microsurgery. Very few cases have been reported in the literature, most of them identified in free flap breast reconstruction. As a result, little data is currently available on the etiology and treatment of this rare complication. Herein, we report a unique case of early venous anastomosis avulsion following free DIEP flap transfer for delayed breast reconstruction. Venous outflow was successfully restored with the use of an interposition vein graft, and the flap survived completely. In addition, the relevant literature is reviewed; and the possible causes, preventive strategies, and management options are analyzed.
Assuntos
Mamoplastia , Náusea e Vômito Pós-Operatórios/complicações , Retalhos Cirúrgicos/irrigação sanguínea , Veias/cirurgia , Trombose Venosa/cirurgia , Anastomose Cirúrgica , Feminino , Humanos , Microcirurgia , Pessoa de Meia-Idade , Terapia de Salvação , Veias/lesões , Veias/transplante , Trombose Venosa/etiologiaRESUMO
Microvascular anastomotic aneurysms are an uncommon complication in reconstructive surgery, which can lead to free flap failure or even threaten the life of the patient. The literature referring to microvascular anastomotic aneurysms was reviewed in order to highlight their clinical presentation, diagnostic work-up, and therapeutic management. Also, a case of a ruptured aneurysm following free transfer of a fibula flap to the lower face is presented. No prospective studies were found. Only few case reports and some sporadic cases in retrospective studies referring to free flap complications were identified. All the aneurysms were false, the main etiologic factor was assumed to be infection, and the presenting signs were either arterial bleeding, as a result of rupture, or the presence of a pulsating mass. No widely accepted therapeutic guidelines were found, and the treatment was tailored to the specific clinical presentation of each case. Regarding the reported case, excision of the ruptured aneurysm and restoration of vascular continuity with a vein graft ensured complete survival of the flap. In conclusion, microvascular anastomotic aneurysms, although uncommon, represent a complication that every reconstructive surgeon should be aware of. Early diagnosis and proper treatment are crucial for a successful outcome. Selection of the appropriate treatment should be based on the presenting sign, the location, the degree of flap neovascularization as well as the condition and quality of the recipient bed; and comprises either ligation of the nutrient artery or excision of the aneurysm and restoration of arterial continuity.
Assuntos
Anastomose Cirúrgica/efeitos adversos , Aneurisma/etiologia , Microcirurgia/efeitos adversos , Procedimentos de Cirurgia Plástica/efeitos adversos , Retalhos Cirúrgicos/efeitos adversos , Aneurisma/patologia , Aneurisma/cirurgia , Face/irrigação sanguínea , Face/cirurgia , Humanos , Masculino , Microcirurgia/métodos , Microvasos/patologia , Microvasos/cirurgia , Pessoa de Meia-Idade , Procedimentos de Cirurgia Plástica/métodos , Retalhos Cirúrgicos/irrigação sanguíneaRESUMO
BACKGROUND: Hepcidin is a 25-aminoacid cysteine-rich iron regulating peptide. Increased hepcidin concentrations lead to iron sequestration in macrophages, contributing to the pathogenesis of anaemia of chronic disease whereas decreased hepcidin is observed in iron deficiency and primary iron overload diseases such as hereditary hemochromatosis. Hepcidin quantification in human blood or urine may provide further insights for the pathogenesis of disorders of iron homeostasis and might prove a valuable tool for clinicians for the differential diagnosis of anaemia. This study describes a specific and non-operator demanding immunoassay for hepcidin quantification in human sera. METHODS AND FINDINGS: An ELISA assay was developed for measuring hepcidin serum concentration using a recombinant hepcidin25-His peptide and a polyclonal antibody against this peptide, which was able to identify native hepcidin. The ELISA assay had a detection range of 10-1500 microg/L and a detection limit of 5.4 microg/L. The intra- and interassay coefficients of variance ranged from 8-15% and 5-16%, respectively. Mean linearity and recovery were 101% and 107%, respectively. Mean hepcidin levels were significantly lower in 7 patients with juvenile hemochromatosis (12.8 microg/L) and 10 patients with iron deficiency anemia (15.7 microg/L) and higher in 7 patients with Hodgkin lymphoma (116.7 microg/L) compared to 32 age-matched healthy controls (42.7 microg/L). CONCLUSIONS: We describe a new simple ELISA assay for measuring hepcidin in human serum with sufficient accuracy and reproducibility.
Assuntos
Anemia/diagnóstico , Peptídeos Catiônicos Antimicrobianos/sangue , Ensaio de Imunoadsorção Enzimática/métodos , Anemia Ferropriva/sangue , Hemocromatose/sangue , Hepcidinas , Doença de Hodgkin/sangue , Humanos , Sensibilidade e EspecificidadeRESUMO
A transmesocolic hernia is an uncommon type of internal hernia. We present a case of an internal hernia, through a congenital defect of the sigmoid mesocolon in a 3-year-old girl referred to our hospital with acute pain in the left abdominal region and vomiting. Because of the progressive worsening of her clinical status, an early laparotomy was performed and the intraoperative findings were consistent with a transmesosigmoid hernia. The hernia's sac contained gangrenous ileum loops, which were resected, and the defect was closed. Postoperative outcome was uneventful and the patient was discharged on the 10th postoperative day.
Assuntos
Hérnia Abdominal/complicações , Íleo/patologia , Obstrução Intestinal/etiologia , Pré-Escolar , Feminino , Hérnia Abdominal/congênito , Hérnia Abdominal/fisiopatologia , Humanos , Obstrução Intestinal/cirurgiaRESUMO
Hepcidin production is homeostatically regulated by iron stores, anemia and hypoxia. We evaluated the effect of iron overload and of ineffective erythropoeisis on hepcidin expression in patients with thalassemia major. Liver hepcidin mRNA levels correlated with hemoglobin concentration and inversely correlated with serum transferrin receptor, erythropoietin and non-transferrin-bound iron. They did not correlate with indices of iron load. Urinary hepcidin levels were disproportionably suppressed in regards to iron burden. We conclude that hepcidin expression is regulated mainly by increased erythropoietic activity rather than by iron load and that hepcidin plays a central regulatory role in iron circulation and iron toxicity in patients with thalassemia.
Assuntos
Peptídeos Catiônicos Antimicrobianos/genética , Eritropoese , Ferro/metabolismo , Talassemia beta/genética , Transfusão de Sangue , Primers do DNA , Transfusão de Eritrócitos , Regulação da Expressão Gênica , Hepcidinas , Humanos , Lactente , Fígado/fisiopatologia , Masculino , Reação em Cadeia da Polimerase , RNA/genética , RNA/isolamento & purificação , Talassemia beta/sangue , Talassemia beta/terapiaRESUMO
Hereditary hyperferritinemia-cataract syndrome (HHCS) is a well-characterized autosomal dominant disease caused by mutations in the iron responsive element (IRE) of ferritin L-chain (FTL) mRNA. Mutations in the IRE result in reduced binding of the trans-acting iron regulatory proteins (IRPs) and hence in upregulation of ferritin L-chain synthesis. The disease is characterized by increased L-ferritin in serum and tissues and early onset of bilateral cataracts. Iron metabolism is normal, and there is no tissue iron overload. At least 25 nucleotide substitutions and deletions in the L-ferritin IRE have been described in families with HHCS, originating from diverse European, Australian and North American populations. We studied the molecular pathogenesis of HHCS in three unrelated kinderships of western Greek origin, with 19 affected members. We identified a relatively rare C39G mutation located in the hexanucleotide loop of L-ferritin IRE. Computational analysis of mRNA folding of mutant FTL IRE predicted that the C39 > G mutation leads to a rearrangement of base pairing in this critical region, which is likely to modify the IRP binding affinity. All subjects with HHCS were heterozygotes for the same C39G mutation. Clinical and laboratory phenotypes were described. Moreover, there was evidence of an association between this FTL IRE stem-loop mutation and very high ferritin levels. Our findings broaden the list of populations where HHCS has been described.
Assuntos
Regiões 5' não Traduzidas/genética , Catarata/genética , Ferritinas/genética , Genes Dominantes , Distúrbios do Metabolismo do Ferro/genética , Mutação Puntual , Regiões 5' não Traduzidas/metabolismo , Catarata/metabolismo , Catarata/patologia , Feminino , Ferritinas/biossíntese , Grécia , Humanos , Distúrbios do Metabolismo do Ferro/metabolismo , Distúrbios do Metabolismo do Ferro/patologia , Masculino , Conformação de Ácido Nucleico , Linhagem , SíndromeRESUMO
Juvenile hemochromatosis (JH) is a severe form of hemochromatosis, which involves rapid iron overload and leads to organ damage, typically before the age of 30. We report a single case of a 25-year-old man suffering from juvenile hemochromatosis, with aggressive clinical manifestations, typically characterized by transaminasemia and progressive erectile dysfunction, due to hypogonadotropic hypogonadism. The clinical case appears interesting, as the patient also had secondary osteoporosis accompanied by increased bone resorption, which prevalently affected trabecular bone. Approximately 6 months after normalization of serum ferritin levels was achieved by frequent phlebotomies, he became eugonadal and bone mineral density of the lumbar spine increased. Our observations suggest that osteoporosis might occur in the state of JH even at a young age, mainly due to the deprivation of sex steroids and the direct tissue toxicity of iron.
Assuntos
Hemocromatose/complicações , Proteínas de Membrana/genética , Osteoporose/etiologia , Adulto , Densidade Óssea , Osso e Ossos/metabolismo , Proteínas Ligadas por GPI , Hemocromatose/genética , Hemocromatose/fisiopatologia , Proteína da Hemocromatose , Humanos , Hipogonadismo/complicações , Masculino , Mutação , Osteoporose/fisiopatologiaRESUMO
Familial Mediterranean fever (FMF) is an inherited disease characterized by recurrent inflammatory polyserositis. Although FMF is classically expected only in Middle East populations, it is becoming evident that the disease affects more groups than initially thought. The disease is associated with a number of mutations of the MEFV gene, which codes for a protein named pyrin. The role of E148Q pyrin gene mutation in the development of FMF remains inconclusive. Some authors believe it causes the disease, whereas others favor the concept of a noncausative role. To understand better the role of this mutation, gathering data from different populations may be of value. We studied 60 Greek cases fulfilling the criteria for FMF diagnosis, 30 cases being a definite FMF diagnosis and 30 a probable diagnosis. Twenty-one of the patients, carried mutation E148Q. One was a homozygote (E148Q/E148Q), and 20 carried mutation E148Q in combination with other mutations (compound heterozygotes). In 6 of the 60 cases studied, no mutations were found. Compared with the results for healthy controls, E148Q mutation is significantly frequent. Because different populations may exhibit different patterns of pyrin mutations, association of the E148Q mutation with FMF should be considered in connection with origin data.
Assuntos
Febre Familiar do Mediterrâneo/genética , Mutação Puntual , Proteínas/genética , Proteínas do Citoesqueleto , Grécia , Humanos , PirinaRESUMO
Hepcidin is the principal regulator of iron absorption in humans. The peptide inhibits cellular iron efflux by binding to the iron export channel ferroportin and inducing its internalization and degradation. Either hepcidin deficiency or alterations in its target, ferroportin, would be expected to result in dysregulated iron absorption, tissue maldistribution of iron, and iron overload. Indeed, hepcidin deficiency has been reported in hereditary hemochromatosis and attributed to mutations in HFE, transferrin receptor 2, hemojuvelin, and the hepcidin gene itself. We measured urinary hepcidin in patients with other genetic causes of iron overload. Hepcidin was found to be suppressed in patients with thalassemia syndromes and congenital dyserythropoietic anemia type 1 and was undetectable in patients with juvenile hemochromatosis with HAMP mutations. Of interest, urine hepcidin levels were significantly elevated in 2 patients with hemochromatosis type 4. These findings extend the spectrum of iron disorders with hepcidin deficiency and underscore the critical importance of the hepcidin-ferroportin interaction in iron homeostasis.
Assuntos
Peptídeos Catiônicos Antimicrobianos/urina , Sobrecarga de Ferro/urina , Adulto , Idoso , Feminino , Hepcidinas , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Mutations of the HJV gene, which maps on chromosome 1q21, underlie most cases of juvenile hemochromatosis. We evaluated the frequency of the most common mutation (G320V) of the HJV gene in the Greek population, since 50% of cases of hereditary hemochromatosis in Greece carry mutations of the HJV gene.