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1.
Chem Biol Interact ; 327: 109162, 2020 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-32524993

RESUMO

Hundreds of millions of people worldwide are exposed to unacceptable levels of carcinogenic inorganic arsenic. Animal models have shown that selenium and arsenic are mutually protective through the formation and elimination of the seleno-bis(S-glutathionyl) arsinium ion [(GS)2AsSe]-. Consistent with this, human selenium deficiency in arsenic-endemic regions is associated with arsenic-induced disease, leading to the initiation of human selenium supplementation trials. In contrast to the protective effect observed in vivo, in vitro studies have suggested that selenite increases arsenite cellular retention and toxicity. This difference might be explained by the rapid conversion of selenite to selenide in vivo. In the current study, selenite did not protect the human hepatoma (HepG2) cell line against the toxicity of arsenite at equimolar concentrations, however selenide increased the IC50 by 2.3-fold. Cytotoxicity assays of arsenite + selenite and arsenite + selenide at different molar ratios revealed higher overall mutual antagonism of arsenite + selenide toxicity than arsenite + selenite. Despite this protective effect, in comparison to 75Se-selenite, HepG2 cells in suspension were at least 3-fold more efficient at accumulating selenium from reduced 75Se-selenide, and its accumulation was further increased by arsenite. X-ray fluorescence imaging of HepG2 cells also showed that arsenic accumulation, in the presence of selenide, was higher than in the presence of selenite. These results are consistent with a greater intracellular availability of selenide relative to selenite for protection against arsenite, and the formation and retention of a less toxic product, possibly [(GS)2AsSe]-.


Assuntos
Arsenitos/toxicidade , Substâncias Protetoras/farmacologia , Ácido Selenioso/farmacologia , Compostos de Selênio/farmacologia , Arsênio/metabolismo , Arsenitos/metabolismo , Células Hep G2 , Humanos , Inativação Metabólica/efeitos dos fármacos , Substâncias Protetoras/metabolismo , Radioisótopos/metabolismo , Ácido Selenioso/metabolismo , Selênio/metabolismo , Compostos de Selênio/metabolismo , Radioisótopos de Selênio/metabolismo
2.
J Environ Radioact ; 218: 106225, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32174444

RESUMO

Atmospheric transport and dispersion models are important tools in radiation protection as they help to estimate the impact of radionuclides released into the atmosphere. In particular, such models can be used in combination with radionuclide observations to estimate unknown source term parameters, or to improve source term estimates obtained through other methods. In this paper, a Bayesian inference system was used to determine the source term parameters and their corresponding credible intervals of a real-world anomalous 75Se release at a nuclear facility in Belgium. Furthermore, a formulation is proposed that not only takes into account true detections, but also true instrumental non-detections, false alarms and real misses. The Bayesian inference system is able to correctly determine the known source location. The Bayesian inference is then refined by fixing the release location and by making stronger assumptions about the release period.


Assuntos
Monitoramento de Radiação , Radioisótopos de Selênio/análise , Academias e Institutos , Teorema de Bayes , Bélgica
3.
Phys Med ; 71: 178-184, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32163887

RESUMO

PURPOSE: Intensity modulated brachytherapy (IMBT) with rotating metal shields enables dose modulation that can better conform to the tumor while reducing OAR doses. In this work, we investigate novel rotating shields, compatible with MRI-compatible tandems used for cervix brachytherapy. Three unique shields were evaluated using the traditional 192Ir source. Additionally, 75Se and 169Yb isotopes were investigated as alternative sources. METHODS: Three different IMBT shields were modeled and simulated in RapidBrachyMCTPS. Each tungsten shield was designed to fit inside a 6 mm-wide MRI-compatible tandem. The active core of the source was replaced with 192Ir, 75Se and 169Yb. Transmission factors (TFs) were calculated and defined as the dose ratio at 1 cm on opposite sides of the shielded tandem on the transverse plane. Polar and azimuthal anisotropy plots were extracted from simulations. Dose homogeneities V200%V100% were calculated for all radionuclide-shield combinations. RESULTS: TFs are favorable for IMBT and ranged between 12.9% and 32.2% for 192Ir, 4.0%-16.1% for 75Se and 1.2-6.4% for 169Yb for all shield designs. Average beam-widths in the polar and azimuthal directions were reduced to the range of 42°-112° and 27°-107°, respectively, for all shield-radionuclide combinations. Dose homogeneities for all the radionuclide-shield combinations were within 12% of the non-IMBT tandem. CONCLUSIONS: This study has quantitatively assessed the influence of various rotating cervical cancer-specific IMBT tandem shields on dosimetry. The dynamic single-channel shields and narrow beam-widths in the polar and azimuthal direction give rise to highly anisotropic distributions. Intermediate-to-high energy radionuclides, 75Se and 169Yb substantially improve the modulation capacity of IMBT and pave the way for treating large and complex cervical cancer without interstitial needle implantation.


Assuntos
Braquiterapia , Imageamento por Ressonância Magnética , Radioterapia de Intensidade Modulada , Neoplasias do Colo do Útero/diagnóstico por imagem , Neoplasias do Colo do Útero/radioterapia , Anisotropia , Feminino , Humanos , Radioisótopos de Irídio , Método de Monte Carlo , Radiometria , Radioisótopos de Selênio , Itérbio
4.
J Environ Radioact ; 213: 106133, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31983443

RESUMO

Batch experiments were performed to study adsorption and desorption of 75Se and 113Sn radiotracers at environmentally representative concentrations of ~0.3 ng L-1 and ~3 ng L-1, respectively. The radiotracers were incubated with wet bulk sediments from the Gironde Estuary and the Rhône River, combining freshwater and coastal seawater salinity (S = 0, S = 32) and three different Suspended Particulate Matter (SPM) concentrations (10 mg L-1, 100 mg L-1, 1000 mg L-1) to simulate six hydrologically contrasting situations for each particle type. Results showed no measurable adsorption for 75Se under the experimental conditions, whereas >90% of 113Sn rapidly adsorbed onto the particles during the first hours of exposure. Adsorption efficiency increased with increasing SPM concentration and seemed to be slightly greater for the Rhône River sediments, potentially related to the intrinsic mineral composition. Desorption of spiked sediments exposed to filtered, unspiked freshwater and seawater only occurred for 113Sn (<15% of the previously adsorbed 113Sn) in the Garonne River sediments. This study provides insights to the potential environmental behaviour of hypothetical radionuclide releases of Se and Sn into highly dynamic and contrasting aquatic systems. Multiple accidental scenarios for the case of the Gironde Estuary and the Rhône River are discussed. These scenarios suggest that the environmental fate of soluble radionuclides like Se will be associated to water hydrodynamics and potentially more bioavailable whereas highly particle-active radionuclides like Sn will follow natural river/estuarine sedimentary regimes. Information on reactivity of radionuclides is important for improving the precision of current approaches aiming at modelling environmental radionuclide dispersion in continent-ocean transition systems.


Assuntos
Monitoramento de Radiação , Salinidade , Poluentes Químicos da Água , Adsorção , Monitoramento Ambiental , Sedimentos Geológicos , Cinética , Rios , Radioisótopos de Selênio , Radioisótopos de Estanho
5.
Brachytherapy ; 19(2): 255-263, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31964601

RESUMO

PURPOSE: Several radionuclides with high (60Co, 75Se) and intermediate (169Yb, 153Gd) energies have been investigated as alternatives to 192Ir for high-dose-rate brachytherapy. The purpose of this study was to evaluate the impact of tissue heterogeneities for these five high- to intermediate-energy sources in prostate and head & neck brachytherapy. METHODS AND MATERIALS: Treatment plans were generated for a cohort of prostate (n = 10) and oral tongue (n = 10) patients. Dose calculations were performed using RapidBrachyMCTPS, an in-house Geant4-based Monte Carlo treatment planning system. Treatment plans were simulated using 60Co, 192Ir, 75Se, 169Yb, and 153Gd as the active core of the microSelectron v2 source. Two dose calculation scenarios were presented: (1) dose to water in water (Dw,w), and (2) dose to medium in medium (Dm,m). RESULTS: Dw,w overestimates planning target volume coverage compared with Dm,m, regardless of photon energy. The average planning target volume D90 reduction was ∼1% for high-energy sources, whereas larger differences were observed for intermediate-energy sources (1%-2% for prostate and 4%-7% for oral tongue). Dose differences were not clinically relevant (<5%) for soft tissues in general. Going from Dw,w to Dm,m, bone doses were increased two- to three-fold for 169Yb and four- to five-fold for 153Gd, whereas the ratio was close to ∼1 for high-energy sources. CONCLUSIONS: Dw,w underestimates the dose to bones and, to a lesser extent, overestimates the dose to soft tissues for radionuclides with average energies lower than 192Ir. Further studies regarding bone toxicities are needed before intermediate-energy sources can be adopted in cases where bones are in close vicinity to the tumor.


Assuntos
Osso e Ossos , Braquiterapia/métodos , Neoplasias da Próstata/radioterapia , Radioisótopos/uso terapêutico , Planejamento da Radioterapia Assistida por Computador , Neoplasias da Língua/radioterapia , Radioisótopos de Cobalto/uso terapêutico , Simulação por Computador , Gadolínio/uso terapêutico , Humanos , Radioisótopos de Irídio/uso terapêutico , Masculino , Doses de Radiação , Dosagem Radioterapêutica , Radioisótopos de Selênio/uso terapêutico , Itérbio/uso terapêutico
6.
Nucleosides Nucleotides Nucleic Acids ; 39(1-3): 131-140, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31608780

RESUMO

Synthesis of selenomethylene-locked nucleic acids nucleoside bearing an adenine base (SeLNA-A) was investigated. We first examined the stereoinversion reaction at 2'-positions of a 5',3'-O-TIPDS-protected 4'-C-(hydroxymethyl)ribosyladenine derivative to give the corresponding arabinosyladenine. After triflation, treatment of the arabinosyladenine derivative with a mixture of selenium and sodium borohydride in ethanol managed to construct the desired SeLNA skeleton. Finally, removal of TIPDS by treating with fluoride gave the SeLNA-A nucleoside. In this study, we found the heat-labile property of SeLNA-A. It is necessary to know more precise characteristics of SeLNA to achieve its oligonucleotides synthesis.


Assuntos
Adenina/química , Oligonucleotídeos/síntese química , Compostos de Selênio/química , Radioisótopos de Selênio/química , Estrutura Molecular
7.
Int J Radiat Oncol Biol Phys ; 105(4): 875-883, 2019 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-31330175

RESUMO

PURPOSE: To investigate differences between prescribed and postimplant calculated dose in 192Ir high-dose-rate endorectal brachytherapy (HDR-EBT) by evaluating dose to clinical target volume (CTV) and organs at risk (OARs) calculated with a Monte Carlo-based dose calculation software, RapidBrachyMC. In addition, dose coverage, conformity, and homogeneity were compared among the radionuclides 192Ir, 75Se, and 169Yb for use in HDR-EBT. METHODS AND MATERIALS: Postimplant dosimetry was evaluated using 23 computed tomography (CT) images from patients treated with HDR-EBT using the 192Ir microSelectron v2 (Elekta AB, Stockholm, Sweden) source and the Intracavitary Mold Applicator Set (Elekta AB, Stockholm, Sweden), which is a flexible applicator capable of fitting a tungsten rod for OAR shielding. Four tissue segmentation schemes were evaluated: (1) TG-43 formalism, (2) materials and nominal densities assigned to contours of foreign objects, (3) materials and nominal densities assigned to contoured organs in addition to foreign objects, and (4) materials specified as in (3) but with voxel mass densities derived from CT Hounsfield units. Clinical plans optimized for 192Ir were used, with the results for 75Se and 169Yb normalized to the D90 of the 192Ir clinical plan. RESULTS: In comparison to segmentation scheme 4, TG-43-based dosimetry overestimates CTV D90 by 6% (P = .00003), rectum D50 by 24% (P = .00003), and pelvic bone D50 by 5% (P = .00003) for 192Ir. For 169Yb, CTV D90 is overestimated by 17% (P = .00003) and rectum D50 by 39% (P = .00003), and pelvic bone D50 is significantly underestimated by 27% (P = .007). Postimplant dosimetry calculations also showed that a 169Yb source would give 20% (P = .00003) lower rectum V60 and 17% (P = .00008) lower rectum D50. CONCLUSIONS: Ignoring high-Z materials in dose calculation contributes to inaccuracies that may lead to suboptimal dose optimization and disagreement between prescribed and calculated dose. This is especially important for low-energy radionuclides. Our results also show that with future magnetic resonance imaging-based treatment planning, loss of CT density data will only affect calculated dose in nonbone OARs by 2% or less and bone OARs by 13% or less across all sources if material composition and nominal mass densities are correctly assigned.


Assuntos
Braquiterapia/métodos , Radioisótopos de Irídio/administração & dosagem , Órgãos em Risco/efeitos da radiação , Radioisótopos/administração & dosagem , Neoplasias Retais/radioterapia , Radioisótopos de Selênio/administração & dosagem , Itérbio/administração & dosagem , Braquiterapia/instrumentação , Fêmur/efeitos da radiação , Humanos , Método de Monte Carlo , Órgãos em Risco/diagnóstico por imagem , Ossos Pélvicos/efeitos da radiação , Dosagem Radioterapêutica , Reto/efeitos da radiação , Tomografia Computadorizada por Raios X , Bexiga Urinária/efeitos da radiação
8.
Neurogastroenterol Motil ; 31(9): e13666, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31225936

RESUMO

BACKGROUND: 23-seleno-25-homo-tauro-cholic acid (SeHCAT) scanning to rule out bile acid diarrhea (BAD) in patients with chronic diarrhea has a high yield. Our previous study showed that patients with terminal ileal (TI) Crohn's disease, TI resection, or cholecystectomy were highly likely to have an abnormal scan. As a result, we encouraged clinicians to use a therapeutic trial of a bile acid sequestrant in these patients, instead of scanning. This may have reduced diagnostic yield of the test, so we examined this issue, as well as factors predicting an abnormal scan, in a large cohort of patients referred subsequently. METHODS: We retrospectively identified 1,071 consecutive patients with chronic diarrhea undergoing SeHCAT scanning at Leeds Teaching Hospitals Trust from 2012 to 2016. We reviewed electronic patient records to obtain information on presenting gastrointestinal symptoms and any proposed risk factors for BAD. BAD was categorized according to subtype and severity. KEY RESULTS: As expected, indications for scanning changed between 2012 and 2016, with a significant reduction in referrals with TI Crohn's disease or resection year-on-year (P < 0.001). Despite this, 457 (42.7%) patients had BAD and there was no downward trend in yield of SeHCAT during the 5 year period (P = 0.39). Overall, 51.6% had type II BAD, 36.1% type III, and 12.3% type I. BAD was mild in 31.7%, moderate in 34.4%, and severe in 33.9%. In total, 653 (61.0%) patients had no known risk factors, other than chronic diarrhea, but 233 (35.7%) of these individuals had BAD, and in 143 (61.4%), this was moderate or severe. CONCLUSIONS AND INFERENCES: Despite reduced referrals for SeHCAT scanning in those with clear risk factors for BAD, the yield remained > 40%. One-third of those without known risk factors had BAD.


Assuntos
Ácidos e Sais Biliares , Diarreia/diagnóstico por imagem , Diarreia/epidemiologia , Radioisótopos de Selênio , Ácido Taurocólico/análogos & derivados , Adulto , Idoso , Ácidos e Sais Biliares/metabolismo , Doença Crônica , Diarreia/metabolismo , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prevalência , Estudos Prospectivos , Cintilografia/métodos , Estudos Retrospectivos , Radioisótopos de Selênio/administração & dosagem , Ácido Taurocólico/administração & dosagem
9.
Z Gastroenterol ; 57(6): 734-739, 2019 Jun.
Artigo em Alemão | MEDLINE | ID: mdl-30986886

RESUMO

When first described in 1976, primary bile acid diarrhea (BAD Type 1) was regarded as a very rare cause of chronic diarrhea. Today, the incidence is estimated as > 1 %. Availability of diagnostic tools varies widely and, in Germany, there is no generally consented recommendation for their use. BAD is still widely underdiagnosed.Since the beginning of the '90 s, we have added a therapeutic trial with cholestyramine to our diagnostic approach of chronic diarrhea. Patients with a positive test were offered a Selenium-homocholic acid taurine (SeHCAT) test for confirmation of bile-acid-diarrhea (BAD), using a 7-day-retention of 20 % as cut-off value.From April 1991 to March 2017, after exclusion of other relevant causes for chronic diarrhea like IBD, celiac disease or microscopic colitis, 70 patients with a positive trial treatment of cholestyramine were identified for evaluation. Sixty of them had a SeHCAT test. Patients with BAD Type 1 and Type 3 were excluded, except for cholecystectomy.85 % (35/41) of patients with BAD Type 1 needed continued medical treatment (median follow-up time 8.3 (1 - 23.6) years). Among them, 68.6 % (24/35) took cholestyramine, 31.4 % (11/35) loperamide or another antidiarrheal treatment. 14.6 % (6/41) of patients reported a spontaneous remission after median 2.9 (0.7 - 5.7) years.In the group of patients with BAD after cholecystectomy, 82 % (8/11) still needed treatment after median 7.7 (1 - 24.5) years; 8 having taken cholestyramine, one patient nothing and two with spontaneous remissions.All (8/8) patients with a normal SeHCAT test (7-day retention > 20 %) had spontaneous relief after median 3.6 (1.2 - 6.3) months.Also, 70 % (7/10) of patients who had not been confirmed by the SeHCAT test still needed treatment after median 4.3 (3.7 - 18.3) years.Based on a trial treatment alone, diagnosis of BAD is possible but not assured. Due to its ubiquitous availability, it should be used consequently if other methods are not available. Despite the well-known shortcomings of cholestyramine, a therapeutic trial should be used more consequently. According to the current literature, using the SeHCAT test in the first place will give significantly better results and unnecessary follow-up examinations can be avoided. However, therapeutic consequences might be modest due to the well-known limitations of cholestyramine. A well-tolerated and licensed alternative to cholestyramine is urgently needed.


Assuntos
Ácidos e Sais Biliares/metabolismo , Diarreia/diagnóstico , Diarreia/tratamento farmacológico , Síndromes de Malabsorção/diagnóstico , Compostos Radiofarmacêuticos/farmacocinética , Radioisótopos de Selênio/farmacocinética , Ácido Taurocólico/análogos & derivados , Doença Crônica , Gastroenterologia , Alemanha , Humanos , Valor Preditivo dos Testes , Cintilografia , Ácido Taurocólico/farmacocinética , Resultado do Tratamento
10.
Anal Chim Acta ; 1064: 1-10, 2019 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-30982506

RESUMO

The unraveling of enzymatic reactions, especially identification of enzymatic substrates or products, is important to elucidate biological processes. Here a selenium-isotopic signature for mass spectrometric identification of enzymatic-related species is demonstrated by using selenium-containing peptides (SePeps) as substrates. Thus a strategy is proposed for rapid and precise assay of multiple enzyme activity. These SePeps can be synthesized by introduction of one selenomethionine residue in the sequence and simply identified in the full-scan mode with the feature of distinctive selenium-isotopic distribution without MS/MS verifications, which proposes a novel solution to the specific identification of enzyme-related species, allows to exclude the interferences of species with tiny mass differences in bio-samples, and meanwhile can offer a judgement on data accuracy for the analysis of enzyme activities. As a proof-of-concept, a method for multiple analysis of two representative enzymes in MCF-7 cell lysate has been developed with the isotopic peak areas of either SePep substrates or enzymatic products with the top intensities. These results could be the foundation to extend the method for more complicated enzyme systems. The selenium-isotopic signature provides a powerful protocol for high-throughput assays of peptide-metabolizing enzymes with enhanced confidence and can be extended to screen enzymatic reaction-related substrates.


Assuntos
Proteína Quinase 3 Ativada por Mitógeno/análise , Peptídeos/química , Selênio/química , Ativador de Plasminogênio Tipo Uroquinase/análise , Ensaios de Triagem em Larga Escala , Humanos , Marcação por Isótopo , Células MCF-7 , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Radioisótopos de Selênio , Espectrometria de Massas em Tandem , Células Tumorais Cultivadas , Ativador de Plasminogênio Tipo Uroquinase/metabolismo
11.
Appl Radiat Isot ; 143: 113-122, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30408634

RESUMO

Positron-emitting 72As is the PET imaging counterpart for beta-emitting 77As. Its parent, no carrier added (n.c.a.) 72Se, was produced for a 72Se/72As generator by irradiating an enriched 7°Ge metal-graphite target via the 70Ge(α, 2 n)72Se reaction. Target dissolution used a fast, environmentally friendly method with 93% radioactivity recovery. Chromatographic parameters of the 72Se/72As generator were evaluated, the eluted n.c.a. 72As was characterized with a phantom imaging study, and the previously reported trithiol and aryl-dithiol ligand systems were radiolabeled with the separated n.c.a. 72As in high yield.


Assuntos
Arsênio/isolamento & purificação , Radioisótopos/isolamento & purificação , Geradores de Radionuclídeos , Compostos Radiofarmacêuticos/isolamento & purificação , Radioisótopos de Selênio/isolamento & purificação , Germânio/química , Germânio/isolamento & purificação , Germânio/efeitos da radiação , Humanos , Isótopos/química , Isótopos/isolamento & purificação , Isótopos/efeitos da radiação , Imagens de Fantasmas , Tomografia por Emissão de Pósitrons , Ensaio Radioligante , Compostos Radiofarmacêuticos/síntese química , Compostos Radiofarmacêuticos/química
12.
Rev Esp Enferm Dig ; 111(1): 40-45, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30284903

RESUMO

INTRODUCTION AND AIM: Crohn's disease (CD) is a form of inflammatory bowel disease and is mainly characterized by diarrhea and abdominal pain. The aim of our study was to analyze the usefulness of performing a 75SeHCAT scan in CD patients with chronic diarrhea and suspected bile acid malabsorption (BAM). In addition, we aimed to determine whether there was a relationship with the clinical features of the disease and a previous bowel resection. PATIENTS AND METHODS: this was an observational cross-sectional study of 39 patients with a diagnosis of CD and chronic diarrhea. All cases underwent a 75SeHCAT scan for BAM diagnosis, after discarding disease activity. RESULTS: the study cohort included 19 females and 20 males. The median age was 44 years and the majority of patients were A2 L1 B1 according to the Montreal classification; 84.6% of patients had undergone a previous bowel resection. BAM was present in 97.4% of patients (100% and 83.3% of patients with and without previous surgery, respectively), which was severe in 92.1% of cases. Treatment with bile acid sequestrants was initiated and a favorable response was obtained in 72.2% of patients. The relationship between BAM degree (moderate or severe), bowel surgery and the response to bile acid sequestrant treatment was also analyzed but not statistically significant. CONCLUSION: BAM is a frequent cause of diarrhea in CD patients in endoscopic or radiological remission. This condition was present in all patients with a history of a bowel resection. A response to bile acid sequestrants treatment was observed in 73% of patients.


Assuntos
Ácidos e Sais Biliares , Doença de Crohn/diagnóstico por imagem , Diarreia/diagnóstico por imagem , Síndromes de Malabsorção/diagnóstico por imagem , Adulto , Endoscopia por Cápsula , Doença Crônica , Doença de Crohn/complicações , Doença de Crohn/metabolismo , Estudos Transversais , Diarreia/etiologia , Feminino , Humanos , Síndromes de Malabsorção/classificação , Masculino , Pessoa de Meia-Idade , Radioisótopos de Selênio , Adulto Jovem
13.
Environ Geochem Health ; 41(2): 1003-1035, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30267320

RESUMO

Selenium (Se) is an important micronutrient and essential trace element for both humans and animals, which exist in the environment ubiquitously. Selenium deficiency is an important issue worldwide, with various reported cases of its deficiency. Low selenium contents in some specific terrestrial environments have resulted in its deficiency in humans. However, high levels of selenium in the geochemical environment may have harmful influences and can cause a severe toxicity to living things. Due to its extremely narrow deficiency and toxicity limits, selenium is becoming a serious matter of discussion for the scientists who deals with selenium-related environmental and health issues. Based on available relevant literature, this review provides a comprehensive data about Se sources, levels, production and factors affecting selenium bioavailability/speciation in soil, characteristics of Se, biogeochemical cycling, deficiency and toxicity, and its environmental transformation to know the Se distribution in the environment. Further research should focus on thoroughly understanding the concentration, speciation, Se cycling in the environment and food chain to effectively utilize Se resources, remediate Se deficiency/toxicity, and evaluate the Se states and eco-effects on human health.


Assuntos
Recuperação e Remediação Ambiental/métodos , Selênio/farmacocinética , Selênio/toxicidade , Solo/química , Animais , Biodegradação Ambiental , Disponibilidade Biológica , Cadeia Alimentar , Humanos , Micronutrientes/farmacocinética , Plantas/química , Selênio/análise , Selênio/deficiência , Radioisótopos de Selênio/análise , Água/química
14.
MAGMA ; 32(1): 163-171, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30387017

RESUMO

In up to 50% of people diagnosed with a common ailment, diarrhea-predominant irritable bowel syndrome, diarrhea results from excess spillage of bile acids into the colon-data emerging over the past decade identified deficient release of a gut hormone, fibroblast growth factor 19 (FGF19), and a consequent lack of feedback suppression of bile acid synthesis as the most common cause. 75Selenium homotaurocholic acid (SeHCAT) testing, considered the most sensitive and specific means of identifying individuals with bile acid diarrhea, is unavailable in many countries, including the United States. Other than SeHCAT, tests to diagnose bile acid diarrhea are cumbersome, non-specific, or insufficiently validated; clinicians commonly rely on a therapeutic trial of bile acid binders. Here, we review bile acid synthesis and transport, the pathogenesis of bile acid diarrhea, the reasons clinicians frequently overlook this disorder, including the limitations of currently available tests, and our efforts to develop a novel 19F magnetic resonance imaging (MRI)-based diagnostic approach. We created 19F-labeled bile acid analogues whose in vitro and in vivo transport mimics that of naturally occurring bile acids. Using dual 1H/19F MRI of the gallbladders of live mice fed 19F-labeled bile acid analogues, we were able to differentiate wild-type mice from strains deficient in intestinal expression of a key bile acid transporter, the apical sodium-dependent bile acid transporter (ASBT), or FGF15, the mouse homologue of FGF19. In addition to reviewing our development of 19F-labeled bile acid analogue-MRI to diagnose bile acid diarrhea, we discuss challenges to its clinical implementation. A major limitation is the paucity of clinical MRI facilities equipped with the appropriate coil and software needed to detect 19F signals.


Assuntos
Ácidos e Sais Biliares/química , Diarreia/diagnóstico por imagem , Imagem por Ressonância Magnética de Flúor-19 , Animais , Transporte Biológico , Testes Diagnósticos de Rotina , Feminino , Fatores de Crescimento de Fibroblastos/metabolismo , Vesícula Biliar/efeitos dos fármacos , Humanos , Intestinos , Masculino , Teste de Materiais , Camundongos , Camundongos Knockout , Transportadores de Ânions Orgânicos Dependentes de Sódio/metabolismo , Radioisótopos de Selênio/química , Simportadores/metabolismo , Ácido Taurocólico/química
15.
Methods Mol Biol ; 1661: 43-60, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-28917036

RESUMO

The selenocysteine (Sec) tRNA[Ser]Sec population consists of two isoforms that differ from each other by a single 2'-O-methylribosyl moiety at position 34 (Um34). These two isoforms, which are encoded in a single gene, Trsp, and modified posttranscriptionally, are involved individually in the synthesis of two subclasses of selenoproteins, designated housekeeping and stress-related selenoproteins. Techniques used in obtaining these isoforms for their characterization include extraction of RNA from mammalian cells and tissues, purifying the tRNA[Ser]Sec population by one or more procedures, and finally resolving the two isoforms from each other. Since some of the older techniques for isolating tRNA[Ser]Sec and resolving the isoforms are used in only a few laboratories, these procedures will be discussed briefly and references provided for more detailed information, while the more recently developed procedures are discussed in detail. In addition, a novel technique that was developed in sequencing tRNA[Ser]Sec for identifying their occurrence in other organisms is also presented.


Assuntos
RNA de Transferência Aminoácido-Específico/genética , Selenoproteínas/genética , Animais , Northern Blotting , Cromatografia de Afinidade , Cromatografia de Fase Reversa , Humanos , Marcação por Isótopo , Conformação de Ácido Nucleico , Biossíntese de Proteínas , RNA de Transferência Aminoácido-Específico/química , Radioisótopos de Selênio , Selenoproteínas/química , Selenoproteínas/isolamento & purificação , Análise de Sequência de RNA
16.
Methods Mol Biol ; 1661: 145-152, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-28917042

RESUMO

Selenium (Se) is an element readily absorbed during the intestinal tract, distributed in the body by means of blood and excreted mainly by urine or feces. Here, we describe the method allowing the determination of the total Se content in biological tissues and fluids by Inductively Coupled Plasma Mass Spectrometry (ICP MS).


Assuntos
Espectrometria de Massas/métodos , Selênio/análise , Animais , Humanos , Radioisótopos de Selênio/análise
17.
Methods Mol Biol ; 1661: 177-192, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-28917045

RESUMO

The trace element selenium (Se) is incorporated into proteins as the amino acid selenocysteine (Sec), which is cotranslationally inserted into specific proteins in response to a UGA codon. Proteins containing Sec at these specific positions are called selenoproteins. Most selenoproteins function as oxidoreductases, while some serve other important functions. There are 25 known selenoprotein genes in humans and 24 in mice. The use of Sec allows selenoproteins to be detected by a convenient method involving metabolic labeling with 75Se. Labeling of cells and whole animals are used for the examination of selenoprotein expression profiles and the investigation of selenoprotein functions. In mammals, nonspecific 75Se insertion is very low, and sensitivity and specificity of selenoprotein detection approaches that of Western blotting. This method allows for the examination of selenoprotein expression and Se metabolism in model and non-model organisms. Herein, we describe experimental protocols for analyzing selenoproteins by metabolic labeling with 75Se both in vitro and in vivo. As an example, the procedure for metabolic labeling of HEK293T human embryonic kidney cells is described in detail. This approach remains a method of choice for the detection of selenoproteins in diverse settings.


Assuntos
Marcação por Isótopo , Radioisótopos de Selênio , Selenoproteínas/análise , Animais , Autorradiografia , Caenorhabditis elegans , Linhagem Celular , Células Cultivadas , Drosophila , Eletroforese em Gel de Poliacrilamida , Humanos , Processamento de Imagem Assistida por Computador , Selenocisteína/análise
18.
Methods Mol Biol ; 1661: 325-335, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-28917055

RESUMO

Disorders of selenoprotein biosynthesis in humans, due to mutations in three genes (SECISBP2, TRU-TCA1-1, and SEPSECS) involved in the selenocysteine insertion pathway, have been described. Patients with SECISBP2 and TRU-TCA1-1 defects manifest a multisystem disorder with a biochemical signature of abnormal thyroid function tests due to the impaired activity of deiodinase selenoenzymes, myopathic features linked to SEPN1 deficiency and phenotypes resulting from increased levels of reactive oxygen species attributable to lack of antioxidant selenoenzymes. In patients harboring SEPSECS mutations, severe, progressive, cerebello-cerebral atrophy (pontocerebellar hypoplasia type 2D) dominates the phenotype and it is not known whether the disorder is associated with thyroid dysfunction.


Assuntos
Estudos de Associação Genética , Doenças Genéticas Inatas/genética , Biossíntese de Proteínas/genética , Selenoproteínas/genética , Western Blotting , Doenças Genéticas Inatas/metabolismo , Glutationa Peroxidase/sangue , Glutationa Peroxidase/metabolismo , Humanos , Marcação por Isótopo , Leucócitos Mononucleares , Peroxidação de Lipídeos , Radioisótopos de Selênio , Selenocisteína/genética , Selenoproteínas/sangue
19.
Int J Radiat Oncol Biol Phys ; 100(1): 270-277, 2018 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-29102279

RESUMO

PURPOSE: Radioisotopes such as 75Se, 169Yb, and 153Gd have photon energy spectra and half-lives that make them excellent candidates as alternatives to 192Ir for high-dose-rate brachytherapy. The aim of the present study was to evaluate the relative biological effectiveness (RBE) of current (192Ir, 125I, 103Pd) and alternative (75Se, 169Yb, 153Gd) brachytherapy radionuclides using Monte Carlo simulations of lineal energy distributions. METHODS AND MATERIALS: Brachytherapy sources (microSelectron v2 [192Ir, 75Se, 169Yb, 153Gd], SelectSeed [125I], and TheraSeed [103Pd]) were placed in the center of a spherical water phantom with a radius of 40 cm using the Geant4 Monte Carlo simulation toolkit. The kinetic energy of all primary, scattered, and fluorescence photons interacting in a scoring volume were tallied at various depths from the source. Electron tracks were generated by sampling the photon interaction spectrum and tracking all the interactions down to 10 eV using the event-by-event capabilities of the Geant4-DNA models. The dose mean lineal energy (y¯D) values were obtained through random sampling of transfer points and overlaying spherical scoring volumes within the associated volume of the tracks. The scoring volume diameter was determined by fitting the y¯D ratio for 125I to its observed RBE. RESULTS: y¯D increased with the increasing distance from the source for 192Ir, 75Se, and 169Yb, remained constant for 153Gd and 125I, and decreased for 103Pd. The diameter at which the y¯D ratio coincided with the RBE of 1.15 to 1.20 for 125I was ∼25 to 40 nm. The RBE (reference 1 MeV photons) at high doses and dose rates for 192Ir, 75Se, 169Yb, 153Gd, 125I, and 103Pd was 1.028 to 1.034, 1.05 to 1.07, 1.12 to 1.15, 1.16 to 1.21, 1.15 to 1.20, and 1.17 to 1.22, respectively. CONCLUSIONS: The radiation quality of the radionuclides under investigation was greater than that of high-energy photons. The present study has provided a set of values to modify the prescription doses for brachytherapy to account for the variation in radiation quality among radionuclides.


Assuntos
Braquiterapia , Radioisótopos/uso terapêutico , Dosagem Radioterapêutica , Eficiência Biológica Relativa , Gadolínio/uso terapêutico , Radioisótopos do Iodo/uso terapêutico , Radioisótopos de Irídio/uso terapêutico , Transferência Linear de Energia , Método de Monte Carlo , Imagens de Fantasmas , Radiometria/métodos , Radioisótopos de Selênio/uso terapêutico , Itérbio/uso terapêutico
20.
Anal Biochem ; 530: 9-16, 2017 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-28476531

RESUMO

Studies have shown that information related to the presence of low-molecular-weight metabolites is frequently lost after deproteinization of complex matrices, such as blood and plasma, during sample preparation. Therefore, the effect of several deproteinization reagents on low-molecular-weight selenium species has been compared by species-specific isotope labeling. Two isotopically enriched selenium tracers were used to mimic models of small inorganic anionic (77Se-selenite) and organic zwitterionic (76Se-selenomethionine) species. The results presented here show that the use of a methanol-acetonitrile-acetone (1:1:1 v/v/v) mixture provided approximately two times less tracer loss from plasma samples in comparison with the classic procedure using acetonitrile, which may not be optimal as it leads to important losses of low-molecular-weight selenium species. In addition, the possible interactions between selenium tracers and proteins were investigated, revealing that both coprecipitation phenomena and association with proteins were potentially responsible for selenite tracer losses during protein precipitation in blood samples. However, coprecipitation phenomena were found to be fully responsible for losses of both tracers observed in plasma samples and of the selenomethionine tracer in blood samples. This successfully applied strategy is anticipated to be useful for more extensive future studies in selenometabolomics.


Assuntos
Proteínas Sanguíneas/análise , Plasma/química , Traçadores Radioativos , Radioisótopos de Selênio/análise , Selênio/análise , Selenometionina/análise , Proteínas Sanguíneas/isolamento & purificação , Espectrometria de Massas , Peso Molecular , Selênio/química , Selênio/isolamento & purificação , Radioisótopos de Selênio/química , Radioisótopos de Selênio/isolamento & purificação , Selenometionina/química , Selenometionina/isolamento & purificação
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