RESUMO
RESEARCH QUESTION: Do heavy metals affect the risk of diminished ovarian reserve (DOR) in women of reproductive age? DESIGN: A total of 139 cases and 153 controls were included between 2016 and 2020. The participants were aged between 18 and 40 years and attended consultations for couple infertility in one of four fertility centres in western France. Cases of DOR were defined as women with an antral follicle count less than 7, anti-Müllerian hormone levels 1.1 ng/ml or less, or both. Controls were frequency matched on age groups and centres, and were women with normal ovarian reserve evaluations, no malformations and menstrual cycles between 26 and 35 days. Heavy metals (lead, mercury, cadmium and chromium) were measured in whole blood at inclusion. Single-exposure associations were examined with multivariable logistic regressions adjusted on potential confounders. Mixture effects were investigated with quantile g-computation and Bayesian kernel machine regression (BKMR). RESULTS: Chromium as a continuous exposure was significantly associated with DOR in unadjusted models (OR 2.07, 95% CI 1.04 to 4.13) but the association was no longer significant when confounders were controlled for (adjusted OR 2.75, 95% CI 0.88 to 8.60). Similarly, a statistically significant association was observed for the unadjusted second tercile of cadmium exposure (OR 1.87, 95% CI 1.06 to 3.30); however, this association was no longer statistically significant after adjustment. None of the other associations tested were statistically significant. Quantile g-computation and BKMR both yielded no significant change of risk of DOR for the mixture of metals, with no evidence of interaction. CONCLUSIONS: Weak signals that some heavy metals could be associated with DOR were detected. These findings should be replicated in other studies.
Assuntos
Metais Pesados , Doenças Ovarianas , Reserva Ovariana , Humanos , Feminino , Adolescente , Adulto Jovem , Adulto , Recém-Nascido , Masculino , Cádmio , Teorema de Bayes , Cromo , Hormônio AntimüllerianoAssuntos
Anemia Hipocrômica , Benzoatos , Hidrazinas , Síndromes Mielodisplásicas , Pirazóis , Transplante de Células-Tronco , Idoso , Aloenxertos , Anemia Hipocrômica/sangue , Anemia Hipocrômica/induzido quimicamente , Anemia Hipocrômica/patologia , Benzoatos/administração & dosagem , Benzoatos/efeitos adversos , Feminino , Humanos , Hidrazinas/administração & dosagem , Hidrazinas/efeitos adversos , Síndromes Mielodisplásicas/sangue , Síndromes Mielodisplásicas/patologia , Síndromes Mielodisplásicas/terapia , Pirazóis/administração & dosagem , Pirazóis/efeitos adversosRESUMO
BACKGROUND: Liver transplantation (LT) is the best treatment for patients with liver cancer or end stage cirrhosis, but it is still associated with a significant mortality. Therefore identifying factors associated with mortality could help improve patient management. The impact of iron metabolism, which could be a relevant therapeutic target, yield discrepant results in this setting. Previous studies suggest that increased serum ferritin is associated with higher mortality. Surprisingly iron deficiency which is a well described risk factor in critically ill patients has not been considered. AIM: To assess the impact of pre-transplant iron metabolism parameters on post-transplant survival. METHODS: From 2001 to 2011, 553 patients who underwent LT with iron metabolism parameters available at LT evaluation were included. Data were prospectively recorded at the time of evaluation and at the time of LT regarding donor and recipient. Serum ferritin (SF) and transferrin saturation (TS) were studied as continuous and categorical variable. Cox regression analysis was used to determine mortality risks factors. Follow-up data were obtained from the local and national database regarding causes of death. RESULTS: At the end of a 95-mo median follow-up, 196 patients were dead, 38 of them because of infections. In multivariate analysis, overall mortality was significantly associated with TS > 75% [HR: 1.73 (1.14; 2.63)], SF < 100 µg/L [HR: 1.62 (1.12; 2.35)], hepatocellular carcinoma [HR: 1.58 (1.15; 2.26)], estimated glomerular filtration rate (CKD EPI Cystatin C) [HR: 0.99 (0.98; 0.99)], and packed red blood cell transfusion [HR: 1.05 (1.03; 1.08)]. Kaplan Meier curves show that patients with low SF (< 100 µg/L) or high SF (> 400 µg/L) have lower survival rates at 36 mo than patients with normal SF (P = 0.008 and P = 0.016 respectively). Patients with TS higher than 75% had higher mortality at 12 mo (91.4% ± 1.4% vs 84.6% ± 3.1%, P = 0.039). TS > 75% was significantly associated with infection related death [HR: 3.06 (1.13; 8.23)]. CONCLUSION: Our results show that iron metabolism imbalance (either deficiency or overload) is associated with post-transplant overall and infectious mortality. Impact of iron supplementation or depletion should be assessed in prospective study.
Assuntos
Infecções/mortalidade , Ferro/metabolismo , Transplante de Fígado/efeitos adversos , Complicações Pós-Operatórias/mortalidade , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/cirurgia , Doença Hepática Terminal/sangue , Doença Hepática Terminal/etiologia , Doença Hepática Terminal/mortalidade , Doença Hepática Terminal/cirurgia , Feminino , Ferritinas/sangue , Ferritinas/metabolismo , Seguimentos , Humanos , Infecções/etiologia , Ferro/sangue , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Complicações Pós-Operatórias/etiologia , Estudos Prospectivos , Estudos Retrospectivos , Medição de Risco/métodos , Fatores de Risco , Taxa de Sobrevida , Transferrina/análise , Transferrina/metabolismoRESUMO
Measurements of inorganic elements in clinical laboratories produce results used for the diagnosis, the treatment and the monitoring of deficiencies or overloads. The main objective of External Quality Assessment Schemes is to verify, on a regular frequency, that clinical laboratory results correspond to the quality requirement for patient care. Therefore, External Quality Assessment Schemes represent an essential component of a laboratory's quality management system. However, External Quality Assessment Schemes within the same analytical field remain heterogeneous for different reasons such as samples, determination of assigned value, acceptable limits, content of the reports. The aim of this review was to describe and illustrate some major critical aspects of External Quality Assessment Schemes based on Occupational and Environmental Laboratory Medicine external quality assessment scheme experience.
Assuntos
Medicina Ambiental , Laboratórios , Medicina do Trabalho , Garantia da Qualidade dos Cuidados de Saúde , Oligoelementos/análise , HumanosRESUMO
Hepcidin has progressively become essential in clinical practice for the diagnosis and follow-up of a large spectrum of diseases. Anyway, its own biochemical and structural characteristics have complicated and delayed the acquisition of a standardized quantifying tool of the peptide.
Assuntos
Hepcidinas/análise , Fatores Etários , Feminino , Regulação da Expressão Gênica , Hepcidinas/química , Hepcidinas/metabolismo , Hepcidinas/fisiologia , Humanos , Imunoensaio/métodos , Inflamação/genética , Inflamação/metabolismo , Inflamação/patologia , MasculinoRESUMO
HFE hereditary hemochromatosis is a chronic illness (ALD n(o) 17 - Maladies métaboliques et héréditaires) which is the first genetic disease in France (60% of all genetic diseases). The list of medical acts and the services supported by the French national health insurance fund are fully codified by the French national authority for health (HAS) in order to reduce unnecessary health care spending. The search for the C282Y mutation of the HFE gene to confirm the diagnosis is supported by French national health insurance fund since 2007 (under certain conditions). Treatment by phlebotomy is well established. It should begin in hospital and is generally well tolerated. Since April 2009, the use of the patient's blood (phlebotomy - blood donations) in French blood centers provides an additional contribution to blood transfusion. However, if this genetic disease is well known to the scientific viewpoint (mechanism and toxicity of iron overload, gene ) and therapeutically (bleeding), the diagnosis is always made too late by ignorance of the symptoms.
Assuntos
Hemocromatose/genética , Hemocromatose/terapia , Testes Genéticos , Hemocromatose/diagnóstico , Hemocromatose/economia , Proteína da Hemocromatose , Antígenos de Histocompatibilidade Classe I/genética , Humanos , Quelantes de Ferro/uso terapêutico , Proteínas de Membrana/genética , Mutação , Equipe de Assistência ao Paciente , Linhagem , FlebotomiaRESUMO
Hereditary hemochromatosis (HH) is a frequent recessive disorder of iron metabolism characterised by systemic iron overload. In Northern Europe, more than 90% of HH patients are homozygous for a mis-sense mutation (C282Y) in the HFE1 gene product. The HFE protein is the heavy chain of a MHC class I-related molecule and associates with beta2 microglobulin and the transferrin receptor. Its precise roles in iron metabolism and in the pathophysiology of HH are still unclear. In order to identify the cellular processing of HFE, an important step towards the understanding of the function of the protein, we stably over-expressed the wild type and mutated forms fused to the Green Fluorescent Protein in a melanocytic MHC class I expressing cell line, the Mel Juso cell line. In wild type and mutant clones, the fusion proteins were not detected at the cell surface but only in the cytoplasm. Their sub-cellular localisation was determined by co-labelling of cells with organite-specific antibodies and confocal microscopy. HFE-GFP followed initially HLA class I intracellular processing but co-localised with transferrin in early endosomes without recycling at the cell surface. The C282Y-GFP fusion protein followed a different folding pathway to exit endoplasmic reticulum. Over-expression of the wild-type protein lead to a decrease in diferric transferrin uptake. Our model will be of use in the elucidation of the functional interaction between intracellular HFE and iron transporters transferrin/transferrin receptor complexes and Slc11A2 (also named N-Ramp2 or DMT1) in different endosomal compartments.
Assuntos
Antígenos de Histocompatibilidade Classe I/metabolismo , Melanoma/metabolismo , Proteínas de Membrana/metabolismo , Transferrina/metabolismo , Antígenos CD/metabolismo , Northern Blotting , Western Blotting , Brefeldina A/farmacologia , Calreticulina/metabolismo , Linhagem Celular Tumoral , Vesículas Revestidas/fisiologia , Proteína Coatomer/metabolismo , Endocitose/fisiologia , Retículo Endoplasmático/fisiologia , Endossomos/fisiologia , Citometria de Fluxo , Regulação Neoplásica da Expressão Gênica , Complexo de Golgi/fisiologia , Proteínas de Fluorescência Verde , Células HeLa/metabolismo , Hemocromatose/metabolismo , Proteína da Hemocromatose , Antígenos de Histocompatibilidade Classe I/genética , Humanos , Proteínas Luminescentes/genética , Proteínas Luminescentes/metabolismo , Melanoma/genética , Melanoma/patologia , Proteínas de Membrana/genética , Microscopia Confocal , Microscopia de Fluorescência , Microtúbulos/fisiologia , Mutação/genética , Glicoproteínas da Membrana de Plaquetas/metabolismo , Transporte Proteico , Receptores da Transferrina/metabolismo , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , Tetraspanina 30 , Transfecção , Microglobulina beta-2/metabolismoRESUMO
Hereditary hemochromatosis (HH), a common autosomal recessive disorder due to a mutation in HFE, which encodes an atypical MHC class I glycoprotein, is characterized by excessive absorption of dietary iron. Little is known however of the apparently complex pathophysiology of HFE involvement in the process of iron influx. Here, in order to tackle the issue in vivo, we decided to target HFE expression exclusively to the relevant tissue, intestinal epithelium. This was achieved by putting HFE under transcriptional control of the rat fatty acid binding protein (Fabpi) promoter. Quite unexpectedly, Fabpi-HFE mice had significantly elevated serum transferrin saturation levels in comparison to those of normal littermates. By a careful, layer by layer analysis of transgene expression along the crypt-villus axis, we were able to affirm that the ectopic expression of transgenic HFE in the differentiated villi enterocytes was responsible for ferric hyperabsorption, a phenomenon exacerbated in the absence of endogenous HFE expression, which we assessed by crossing the transgene onto an HFE(-/-) (knockout) background. This forced dichotomy between the absence of HFE in the crypt and expression in the villi provides experimental support that HFE functions as a "gatekeeper," regulating the cross-talk between the crypt and villi enterocytes and thereby modulating the avidity of mature enterocytes for dietary iron.