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OBJECTIVES: This article defines analytical performance specifications (APS) for evaluating laboratory proficiency through an external quality assessment scheme. METHODS: Standard deviations for proficiency assessment were derived from Thompson's characteristic function applied to robust data calculated from participants' submissions in the Occupational and Environmental Laboratory Medicine (OELM) external quality assurance scheme for trace elements in serum, whole blood and urine. Characteristic function was based on two parameters: (1) ß - the average coefficient of variation (CV) at high sample concentrations; (2) α - the average standard deviation (SD) at low sample concentrations. APSs were defined as 1.65 standard deviations calculated by Thompson's approach. Comparison between OELM robust data and characteristic function were used to validate the model. RESULTS: Application of the characteristic function allowed calculated APS for 18 elements across three matrices. Some limitations were noted, particularly for elements (1) with no sample concentrations near analytical technique limit of detection; (2) exhibiting high robust CV at high concentration; (3) exhibiting high analytical variability such as whole blood Tl and urine Pb; (4) with an unbalanced number of robust SD above and under the characteristic function such as whole blood Mn and serum Al and Zn. CONCLUSIONS: The characteristic function was a useful means of deriving APS for trace elements in biological fluids where biological variation data or outcome studies were not available. However, OELM external quality assurance scheme data suggests that the characteristic functions are not appropriate for all elements.
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Zinc is involved in the expression and function of various transcription factors, including the hypoxia-inducible factor-1 (HIF-1). HIF-1 and its target gene endothelin-1 (ET-1) are activated by intermittent hypoxia (IH), one of the main consequences of obstructive sleep apnea (OSA), and both play a key role in the cardiovascular consequences of IH. Because OSA and IH are associated with zinc deficiency, we investigated the effect of zinc deficiency caused by chelation on the HIF-1/ET-1 pathway and its functional consequences in endothelial cells. Primary human microvascular endothelial cells (HMVEC) were incubated with submicromolar doses of the zinc-specific membrane-permeable chelator N,N,N',N'-tetrakis(2-pyridylmethyl)-ethylene diamine (TPEN, 0.5 µM) or ET-1 (0.01 µM) with or without bosentan, a dual ET-1-receptor antagonist. HIF-1α expression was silenced by transfection with specific siRNA. Nuclear HIF-1 content was assessed by immunofluorescence microscopy and Western blot. Migratory capacity of HMVEC was evaluated with a wound-healing scratch assay. Zinc chelation by TPEN exposure induced the translocation of the cytosolic HIF-1α subunit of HIF-1 to the nucleus as well as an HIF-1-mediated ET-1 secretion by HMVEC. Incubation with either TPEN or ET-1 increased endothelial wound-healing capacity. Both HIF-1α silencing or bosentan abolished this effect. Altogether, these results suggest that zinc deficiency upregulates ET-1 signaling through HIF-1 activation and stimulates endothelial cell migration, suggesting an important role of zinc in the vascular consequences of IH and OSA mediated by HIF-1-ET- signaling.
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Movimento Celular/efeitos dos fármacos , Quelantes/farmacologia , Células Endoteliais/efeitos dos fármacos , Endotelina-1/metabolismo , Etilenodiaminas/farmacologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Zinco/deficiência , Transporte Ativo do Núcleo Celular , Bosentana/farmacologia , Células Cultivadas , Células Endoteliais/metabolismo , Antagonistas dos Receptores de Endotelina/farmacologia , Endotelina-1/genética , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Via Secretória , Transdução de SinaisRESUMO
Iron is an essential nutrient which must be provided in sufficient amounts to support growth of eukaryotic cells. All organisms devote specialized pathways to ensure proper delivery. Yet, a quantitative assessment of the intra-cellular iron concentration needed to allow the cell cycle to proceed in mammalian cells is missing. Starting from iron-depleted cell lines or primary hematopoietic progenitors prepared with clinically implemented iron chelators, replenishment via transferrin and other iron sources has been quantitatively monitored through the main endogenous markers of the cellular iron status, namely proteins involved in the uptake (transferrin receptor), the storage (ferritin), and the sensing (Iron Regulatory Proteins) of iron. When correlated with measurements of iron concentrations and indicators of growth, this minimally intrusive approach provided an unprecedented estimate of the intracellular iron concentration acting upon iron-centered regulatory pathways. The data were analyzed with the help of a previously developed theoretical treatment of cellular iron regulation. The minimal cellular iron concentration required for cell division was named functional iron concentration (FIC) to distinguish it from previous estimates of the cellular labile iron. The FIC falls in the low nanomolar range for all studied cells, including hematopoietic progenitors. These data shed new light on basic aspects of cellular iron homeostasis by demonstrating that sensing and regulation of iron occur well below the concentrations requiring storage or becoming noxious in pathological conditions. The quantitative assessment provided here is relevant for monitoring treatments of conditions in which iron provision must be controlled to avoid unwanted cellular proliferation.
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Células-Tronco Hematopoéticas/citologia , Células-Tronco Hematopoéticas/metabolismo , Espaço Intracelular/metabolismo , Ferro/farmacologia , Antígenos CD34/metabolismo , Apoproteínas/metabolismo , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Células-Tronco Hematopoéticas/efeitos dos fármacos , Humanos , Quelantes de Ferro/farmacologia , Transferrina/metabolismoRESUMO
BACKGROUND: Proficiency testing or external quality assessment schemes (PT/EQASs) are an important method of assessing laboratory performance. As each scheme establishes assigned values and acceptable ranges for the analyte according to its own criteria, monitoring of participant performance varies according to the scheme and can lead to conflicting conclusions. METHODS: Standard deviations (SDs) for PT were derived from Thompson's and biological variation models applied to blood and urine manganese (Mn) robust data from four EQASs from North America and Europe. The fitness for purpose was verified by applying these SDs to individual results. RESULTS: Using Thompson characteristic function the relationship between SD and Mn concentration, expressed in nmol/L was the square root of [19.72+(0.07712×Mn concentration2)] for blood and the square root of [6.772+(0.09852×Mn concentration2)] for urine. While the biological variation model was not suitable for urine, it produced an acceptable range for blood as ±54.4 nmol/L (assigned value ≤320 nmol/L) or 17% (assigned value >320 nmol/L). For blood, individual performance evaluated by the two approaches led to similar conclusions. CONCLUSIONS: The biological variation model can be used to propose quality specifications for blood, however it could not be applied to urine. The Thompson characteristic function model could be applied to derive quality specifications for Mn in urine and, to a lesser extent in blood. The more lenient quality specifications for blood highlight the difficulty of determining Mn in this matrix. Further work is needed to harmonize PT, such as using assigned ranges for the specimens.
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Técnicas de Laboratório Clínico/normas , Manganês/sangue , Manganês/urina , HumanosAssuntos
Eritrócitos/química , Iodo/sangue , Oligoelementos/sangue , Análise de Variância , Cobre/análise , Cobre/sangue , Eritrócitos/citologia , Voluntários Saudáveis , Humanos , Iodo/análise , Manganês/análise , Manganês/sangue , Mercúrio/análise , Mercúrio/sangue , Espectrofotometria Atômica , Temperatura , Oligoelementos/análise , Zinco/análise , Zinco/sangueRESUMO
The link between iron status and cognition has been established in infants and children, yet evidence in adults is scant and heterogeneous. We examined sex- and menopause-specific cross-time associations of iron status with cognition in the French Supplémentation en Vitamines et Minéraux Antioxydants Study cohort (1539 men, 1431 pre-/perimenopausal women, 962 postmenopausal women). Serum ferritin and hemoglobin data were obtained in 1995. Cognition was assessed after a mean of 13 y through 6 validated instruments, including the RI-48 cued recall test, phonemic and semantic fluency tasks, forward and backward digit span tasks, and a trail-making test. The standardized individual test scores were summed to form a composite cognitive performance measure. Associations between ferritin and hemoglobin and subsequent cognitive performance were examined through multivariable linear regression. Among men, no significant associations were observed. In postmenopausal women, an inverse association was found between ferritin and phonemic fluency (adjusted ß: -0.11; 95% CI: -0.21, -0.01). Significant inverse associations between ferritin and both the composite cognitive measure (adjusted ß: -0.09; 95% CI: -0.17, -0.00) and the forward digit span scores (adjusted ß: -0.13; 95% CI: -0.22, -0.03) were observed only among premenopausal women aged ≥ 46 y at baseline. No significant findings with hemoglobin emerged. This study supports an inverse association between midlife iron status and subsequent cognitive performance that is sex- and menopause-dependent. Given the urgent need for prevention research on age-related disorders, future investigations of iron status and cognition are warranted. The study is registered at www.clinicaltrials.gov as NCT00272428.
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Cognição , Ferro/sangue , Perimenopausa , Método Duplo-Cego , Feminino , Ferritinas/sangue , Hemoglobinas/análise , Humanos , Pessoa de Meia-Idade , PlacebosRESUMO
TRPC6 are plasma membrane cation channels. By means of live-cell imaging and spectroscopic methods, we found that HEK cells expressing TRPC6 channels (HEK-TRPC6) are enriched in zinc and sulphur and have a reduced copper content when compared to HEK cells and HEK cells expressing TRPC3 channels (HEK-TRPC3). Hence, HEK-TRPC6 cells have larger pools of mobilizable Zn2+ and are more sensitive to an oxidative stress. Synchrotron X-ray fluorescence experiments showed a higher zinc content in the nuclear region indicating that the intracellular distribution of this metal was influenced by the over-expression of TRPC6 channels. Their properties were investigated with the diacylglycerol analogue SAG and the plant extract hyperforin. Electrophysiological recordings and imaging experiments with the fluorescent Zn2+ probe FluoZin-3 demonstrated that TRPC6 channels form Zn2+-conducting channels. In cortical neurons, hyperforin-sensitive channels co-exist with voltage-gated channels, AMPA and NMDA receptors, which are known to transport Zn2+. The ability of these channels to regulate the size of the mobilizable pools of Zn2+ was compared. The data collected indicate that the entry of Zn2+ through TRPC6 channels can up-regulate the size of the DTDP-sensitive pool of Zn2+. By showing that TRPC6 channels constitute a Zn2+ entry pathway, our study suggests that they could play a role in zinc homeostasis.
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Canais de Cátion TRPC/metabolismo , Zinco/metabolismo , Linhagem Celular , Colorimetria , Corantes Fluorescentes/metabolismo , Homeostase , Humanos , Canal de Cátion TRPC6RESUMO
Phthalates are abundantly produced plasticizers, and di(ethylhexyl) phthalate (DEHP) is the most widely used derivative in various consumer products and medical devices. Animal studies show that DEHP and various other phthalates cause reproductive and developmental toxicity. Although the evidences are limited, it seems reasonable that DEHP may have a potential for similar adverse effects in humans. Such concerns are increasing, particularly for the developing reproductive system of male infants and children. By taking into account the essentiality of selenium (Se) in testicular structure and functions and the high prevalence of inadequate Se intake in various part of the world, this study was designed to investigate the testicular toxicity of DEHP in Se-deficient male rats and to examine the possible preventive effects of Se supplementation on phthalate toxicity. Se deficiency was generated by feeding 3-week-old Sprague-Dawley rats with a ≤0.05 Se mg/kg diet for 5 weeks. Supplementation groups were on a 1 mg Se/kg diet, and DEHP-treated groups received a 1,000 mg/kg dose by gavage during the last 10 days of the feeding period. Testicular histopathology, sperm count and motility, and sperm morphology were examined, and plasma levels of sex hormones were measured. Toxicity and antiandrogenic effects of DEHP were evidenced by disturbed testicular histology and spermatogenesis, diminished testosterone, leutinizing hormone (LH) and follicle stimulating hormone (FSH) levels, and sperm motility. The effects of DEHP were much more pronounced in Se-deficient rats, whereas Se supplementation was found to be protective, reflecting its regulating role in cellular redox equilibrium.
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Suplementos Nutricionais , Dietilexilftalato/toxicidade , Disruptores Endócrinos/toxicidade , Reprodução/efeitos dos fármacos , Selênio , Animais , Interpretação Estatística de Dados , Epididimo/efeitos dos fármacos , Epididimo/metabolismo , Epididimo/patologia , Hormônio Foliculoestimulante/sangue , Fígado/efeitos dos fármacos , Fígado/patologia , Hormônio Luteinizante/sangue , Masculino , Tamanho do Órgão/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Selênio/administração & dosagem , Selênio/deficiência , Contagem de Espermatozoides , Motilidade dos Espermatozoides/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos , Espermatozoides/patologia , Testículo/efeitos dos fármacos , Testículo/metabolismo , Testículo/patologiaRESUMO
In the present study, we evaluate the effect of the co-exposure to static magnetic field (SMF) and selenium (Se) on the antioxidant vitamins A and E levels and some other parameters of oxidative stress in rat. Sub-acute exposure of male adult rats to a uniform SMF (128 mT, 1 h/day during 5 consecutive days) increased plasma activity of glutathione peroxidase (+35%) but decreased α-tocopherol (-67%) and retinol levels (-41%). SMF exposure failed to alter the plasmatic thiobarbituric acid-reactive species (TBARs), total thiol groups and selenium concentrations. Sub-chronic administration of Se (Na(2)SeO(3), 0.2 mg/L, for 30 consecutive days, per os) ameliorated the antioxidant capacities in SMF-treated rats. Our investigation demonstrated that sub-acute exposure to SMF induced oxidative stress, which may be prevented by a pretreatment with selenium.
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Antioxidantes/farmacologia , Campos Eletromagnéticos/efeitos adversos , Estresse Oxidativo/efeitos dos fármacos , Compostos de Selênio/farmacologia , Vitamina A/sangue , alfa-Tocoferol/sangue , Animais , Modelos Animais de Doenças , Esquema de Medicação , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Ratos , Ratos Wistar , Ácido Selênico , Substâncias Reativas com Ácido TiobarbitúricoRESUMO
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.
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Medicina Ambiental , Laboratórios , Medicina do Trabalho , Garantia da Qualidade dos Cuidados de Saúde , Oligoelementos/análise , HumanosRESUMO
Cadmium (Cd) is a metal which may participate in the development of type II diabetes even if Cd exposure levels are mild. However, experimental studies focusing on daily environmentally relevant doses are scarce, particularly for glucose metabolism of the offspring of chronically exposed mothers. The aim is to measure the impact of maternal low level Cd exposure on glucose and lipid metabolism of offspring. Female rats were exposed to 0, 50 or 500⯵g.kg-1.d-1 of CdCl2, 21 days before mating and during 21 days of gestation and 21 days of lactation. Pups exposure was organized in 3 groups (control, Cd1, Cd2) according to renal dams' Cd burden. Parameters of glucose and lipid metabolisms were measured for the pups on post-natal day 21, 26 and 60. Maternal Cd exposure led to significant amounts of Cd in the liver and kidney of pups. At weaning, insulin secretion upon glucose stimulation was unchanged, but the removal of circulating glucose was slower for pups born from the lowest impregnated dams (Cd1). Five days after, glucose tolerance of all groups was identical. Thus, this loss of insulin sensitivity was reversed, in part by increased adiponectin secretion for the Cd1 group. Furthermore, pups from dams accumulating the highest levels of Cd (Cd2) exhibited a compensatory increased insulin pancreatic secretion, together with increased circulating non-esterified fatty acids, indicating the establishment of insulin resistance, 2 months after birth. This study has demonstrated the influence of maternal exposure to low levels of Cd on glucose homeostasis in the offspring that might increase the risk of developing type II diabetes later in life.
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Cádmio/química , Diabetes Mellitus Tipo 2/metabolismo , Glucose/química , Metabolismo dos Lipídeos/fisiologia , Animais , Modelos Animais de Doenças , Feminino , Exposição Materna , Gravidez , Ratos , DesmameRESUMO
INTRODUCTION: Occurrence of multiple brain metastases is a critical evolution of many cancers with significant neurological and overall survival consequences, despite new targeted therapy and standard whole brain radiotherapy (WBRT). A gadolinium-based nanoparticle, AGuIX, has recently demonstrated its effectiveness as theranostic and radiosensitiser agent in preclinical studies. The favourable toxicity profile in animals and its administration as a simple intravenous injection has motivated its use in patients with this first in human study. METHODS AND ANALYSIS: The NANO-RAD study is a phase I, first in human injection, monocentric, open-label, dose-escalation study to investigate the safety, the tolerability and the spectrum of side effects of AGuIX in combination with WBRT (30 Gy, 10 fractions of 3 Gy) for patients with multiple brain metastases. Five dose escalation cohorts are planned: 15, 30, 50, 75 and 100 mg/kg. A total of 15-18 patients will be recruited into this trial. The primary objective is to determine the maximum-tolerated dose of AGuIX nanoparticles combined with WBRT for the treatment of multiple brain metastases. Toxicity will be assessed using the National Cancer Institute Common Toxicity Criteria V.4.03. Secondary objectives are pharmacokinetic profile, distribution of AGuIX in metastases and surrounding healthy tissue visualised by MRI, intracranial progression-free survival and overall survival. Intracranial response will be determined according to Response Evaluation Criteria in Solid Tumour Criteria V.1.1 comparing MRI performed prior to treatment and at each follow-up visits. ETHICS AND DISSEMINATION: Approval was obtained from the ethics committee Sud Est V, France (Reference number 15-CHUG-48). The study was approved by the French National Agency for the Safety of Medicines and Health Products (ANSM) (Reference number 151519A-12). The results will be published in peer-reviewed journals or disseminated through national and international conferences. TRIAL REGISTRATION NUMBER: NCT02820454; Pre-results.
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Neoplasias Encefálicas/radioterapia , Gadolínio/administração & dosagem , Nanopartículas Metálicas/administração & dosagem , Radiossensibilizantes/administração & dosagem , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/patologia , Ensaios Clínicos Fase I como Assunto , Terapia Combinada , Fracionamento da Dose de Radiação , Imageamento por Ressonância Magnética , Neoplasias Primárias Múltiplas , Radioterapia/métodos , Resultado do TratamentoRESUMO
Nanomaterials have gained much attention for their use and benefit in several fields. Iron Oxide Nanoparticles (IONPs) have been used in Biomedicine as contrast agents for imaging cancer cells. However, several studies reported the potential toxicity of those nanoparticles in different models, especially in cells. Therefore, in our present study, we investigated the effects of IONPs on the SH-SY5Y neuroblastoma cell line. We carried out cytotoxic and genotoxic studies to evaluate the phenotypic effects, and proteomic investigation to evaluate the molecular effects and the mechanisms by which this kind of NPs could induce toxicity. Our results showed that the use of three different sizes of IONPs (14, 22 and 30 nm) induced cell detachment, cell morphological changes, size, and concentration-dependent IONP internalization and cell mortality. IONPs induced slight genotoxic damage assayed by modified comet assay without affecting cell cycle, mitochondrial function, membrane integrity, intracellular calcium level, and without inducing ROS generation. All the studies were performed to compare also the effects of IONPs to the ferric iron by incubating cells with equivalent concentration of FeCl3. In all tests, the NPs exhibited more toxicity than the ferric iron. The proteomic analysis followed by gene ontology and pathway analysis evidenced the effects of IONPs on cytoskeleton, cell apoptosis, and cancer development. Our findings provided more information about IONP effects on human cells and especially on cancer cell line.
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Apoptose/efeitos dos fármacos , Dano ao DNA , Compostos Férricos/toxicidade , Nanopartículas/toxicidade , Proteoma/metabolismo , Animais , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Ensaio Cometa , Compostos Férricos/química , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Nanopartículas/química , Tamanho da Partícula , Proteômica , Espécies Reativas de Oxigênio/metabolismoRESUMO
Iron Oxide Nanoparticles (IONPs) are used in several fields of application, mainly in the biomedical field for their magnetic properties and in food additive known as "E172" for their colour. In the present investigation, we focused on IONP effects on Wistar rat following acute oral exposure. We performed a multiscale physiopathological investigation in order to elucidate potential toxic effects linked to IONP ingestion, especially on cognitive capacities, trace element distribution, blood constituents, organ functions, organ structure and iron deposit. We demonstrated that oral exposure to IONPs induces disturbances of certain parameters depending on the dose. Interestingly, the histopathological examination evidenced inflammatory effects of IONPs in the liver with iron deposits in hepatocytes and Kuppfer cells. Neurobehavioral examination showed that oral exposure to IONPs did not affect nor rat emotions, exploration and locomotion capacities, nor spatial reference memory status. Furthermore, oral administration of IONPs did not disrupt the trace element homeostasis nor in the liver neither in the stomach. Altogether, our study evidenced low signs of toxicity, but some effects lead us to a careful use of these NPs. Thereby, their use in foods should be further studied to better evaluate the potential toxic risks of the oral exposure to IONPs.
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Cognição/efeitos dos fármacos , Exposição Dietética , Compostos Férricos/análise , Compostos Férricos/farmacocinética , Nanopartículas Metálicas , Oligoelementos/farmacocinética , Animais , Comportamento Animal/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Testes de Química Clínica , Compostos Férricos/química , Testes Hematológicos , Homeostase , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Masculino , Nanopartículas Metálicas/química , Tamanho do Órgão/efeitos dos fármacos , Ratos Wistar , Distribuição Tecidual , Testes de Toxicidade Aguda/métodosRESUMO
Many solid tumors and their metastases are still resistant to current cancer treatments such as chemo- and radiotherapy. The presence of a small population of Cancer Stem Cells in tumors is held responsible for relapses. Moreover, the various physical barriers of the organism (e.g. blood-brain barrier) prevent many drugs from reaching the target cells. In order to alleviate this constraint, we suggest a Trojan horse strategy consisting of intravascular injection of macrophages loaded with therapeutic nanoparticles (an iron nanoparticle-based solution marketed under the name of FERINJECT®) to bring a high quantity of the latter to the tumor. The aim of this article is to assess the response of primary macrophages to FERINJECT® via functional assays in order to ensure that the macrophages loaded with these nanoparticles are still relevant for our strategy. Following this first step, we demonstrate that the loaded macrophages injected into the bloodstream are able to migrate to the tumor site using small-animal imaging. Finally, using synchrotron radiation, we validate an improvement of the radiotherapeutic effect when FERINJECT®-laden macrophages are deposited at the vicinity of cancer cells and irradiated.
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BACKGROUND: Trace element external quality assessment schemes monitor laboratory performance and provide a stimulus for improvement in accuracy. However, monitoring of participant performance varies according to the scheme and can lead to conflicting conclusions. METHODS: Quality specifications based on biological intra- and interindividual variability were calculated and compared to those currently used by various trace element external quality assessment schemes for plasma or serum copper, zinc, and selenium concentrations. For this purpose, we evaluated results reported by participating laboratories in different schemes, at key concentrations, using z scores. RESULTS: Minimal quality specifications developed from the biological intra- and interindividual variability were, for Cu, +/-0.84 micromol/L or 12% of the assigned target concentration, whichever is greater; for Zn, +/-1.20 micromol/L or 15% of the assigned target concentration, whichever is greater; and for Se, +/-0.072 micromol/L or 12% of the assigned target concentration, whichever is greater. Reported performance of the participating laboratories depended on analyte, concentration, and the selected quality specification. In addition, the most commonly used methods for the determination of Cu, Zn, and Se may give different results. CONCLUSIONS: The proposed minimal quality specifications based on biological variation are generally slightly less stringent than those currently in use, although they do not drastically change the performance evaluation in the different schemes. These specifications are a first step in the harmonization of practices among the schemes and remain to be evaluated.
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Cobre/sangue , Controle de Qualidade , Selênio/sangue , Espectrofotometria Atômica/métodos , Zinco/sangue , Humanos , Reprodutibilidade dos Testes , Espectrofotometria Atômica/normasRESUMO
Rickets has emerged as a public-health problem in Bangladesh during the past two decades, with up to 8% of children clinically affected in some areas. Insufficiency of dietary calcium is thought to be the underlying cause, and treatment with calcium (350-1,000 mg elemental calcium daily) is curative. Despite this apparently simple treatment, little is known about the most appropriate management of bone deformities of affected children, and further studies are needed to determine the details of dosing and duration of calcium therapy, the role of bracing, and specific indications for surgical intervention. Effective preventive measures that can feasibly reach entire communities are needed, and these may differ between various affected regions.
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Cálcio da Dieta/administração & dosagem , Cálcio/deficiência , Saúde Pública , Raquitismo/epidemiologia , Bangladesh/epidemiologia , Cálcio da Dieta/uso terapêutico , Criança , Pré-Escolar , Relação Dose-Resposta a Droga , Feminino , Previsões , Humanos , Lactente , Masculino , Raquitismo/tratamento farmacológico , Raquitismo/prevenção & controle , Fatores de Tempo , Resultado do Tratamento , Deficiência de Vitamina D/complicações , Deficiência de Vitamina D/metabolismoRESUMO
Engineered nanomaterials are used in various applications due to their particular properties. Among them, Iron Oxide Nanoparticles (Fe2O3-NPs) are used in Biomedicine as theranostic agents i.e. contrast agents in Magnetic Resonance Imaging and cancer treatment. With the increasing production and use of these Fe2O3-NPs, there is an evident raise of Fe2O3-NPs exposure and subsequently a higher risk of adverse outcomes for the environment and Human. In the present paper, we investigated the effects of an intravenous daily Fe2O3-NPs exposure on Wistar rat for one week. As results, we showed that several hematological parameters and transaminase (ALT and AST) levels as well as organ histology remained unchanged in treated rats. Neither the catecholamine levels nor the emotional behavior and learning / memory capacities of rats were impacted by the sub-acute intravenous exposure to Fe2O3-NPs. However, iron level in plasma and iron content homeostasis in brain were disrupted after this exposure. Thus, our results demonstrated that Fe2O3-NPs could have transient effects on rat but the intravenous route is still safer that others which is encouraging for their use in medical and/or biological applications.