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2.
Sci Rep ; 12(1): 11259, 2022 07 04.
Artigo em Inglês | MEDLINE | ID: mdl-35788623

RESUMO

SLC26A4 is a known iodide transporter, and is localized at the apical membrane of thyrocytes. Previously, we reported that SLC26A7 is also involved in iodide transport and that Slc26a7 is a novel causative gene for congenital hypothyroidism. However, its detailed role in vivo remains to be elucidated. We generated mice that were deficient in Slc26a7 and Slc26a4 to delineate differences and associations in their roles in iodide transport. Slc26a7-/- mice showed goitrous congenital hypothyroidism and mild growth failure on a normal diet. Slc26a7-/- mice with a low iodine environment showed marked growth failure. In contrast, Slc26a4-/- mice showed no growth failure and hypothyroidism in the same low iodine environment. Double-deficient mice showed more severe growth failure than Slc26a7-/- mice. RNA-seq analysis revealed that the number of differentially expressed genes (DEGs) in Slc26a7-/- mice was significantly higher than that in Slc26a4-/- mice. These indicate that SLC26A7 is more strongly involved in iodide transport and the maintenance of thyroid function than SLC26A4.


Assuntos
Antiportadores de Cloreto-Bicarbonato/metabolismo , Hipotireoidismo Congênito , Iodo , Transportadores de Sulfato/metabolismo , Animais , Antiportadores de Cloreto-Bicarbonato/genética , Hipotireoidismo Congênito/genética , Iodetos , Iodo/metabolismo , Proteínas de Membrana Transportadoras/genética , Proteínas de Membrana Transportadoras/metabolismo , Camundongos , Transportadores de Sulfato/genética
3.
Tohoku J Exp Med ; 256(1): 73-84, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-35082185

RESUMO

Suicide is an important public health issue for adolescents. To investigate the risk and protective factors for adolescent suicide, a cross-sectional questionnaire-based survey was conducted at a junior high school (n = 379) in Japan in 2018. After obtaining survey data, we conducted univariate and logistic regression analyses to test for associations between suicidal ideation and several factors, including worries (i.e., about school life, interpersonal relationships at school, family life, interpersonal relationships at home, and academic performance), perceived support from school staff and family members, and social capital. In this context, the existence of trustful relationships between classmates was used as indicators of social capital. The results showed that the prevalence of suicidal ideation was 10.5%. The risk of suicidal ideation was increased by worries about 1) interpersonal relationships at school, 2) interpersonal relationships at home, and 3) academic performance, but was decreased by social support from family members and trusting relationships. Further, the rate of suicidal ideation was higher among students who expressed all these three worries when compared to those who expressed two or fewer worries. In addition, looking at students who expressed all these three worries simultaneously, the rate of suicidal ideation was higher among those with lower levels of support from family members and fewer trustful relationships. Our results suggest that the prevention of adolescent suicide should include strategies for reducing worries about interpersonal relationships at school/home and academic performance while finding ways to enhance family support and classmate social capital.


Assuntos
Desempenho Acadêmico , Capital Social , Adolescente , Estudos Transversais , Humanos , Japão , Fatores de Risco , Apoio Social , Estudantes , Ideação Suicida
5.
Int J Phytoremediation ; 24(9): 893-901, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34613832

RESUMO

Many studies have demonstrated the Eichhornia crassipes (water hyacinth) potency in removing heavy metals, but the plant's potential for sorption of gadolinium (Gd) has not yet been investigated. In this study, water hyacinth was grown in a glass container for 30 days with either GdCl3 or Gd-based contrast agent (GBCA; gadoterate) with water obtained from the Tone River. On the day 30, the Gd concentration in both the water and the plants was measured by mass spectrometry (ICP-MS). After 30 days, 98.5% of GdCl3 in the water had been absorbed by the roots, and 3.5% of Gd was transferred to the leaves. On the other hand, the water hyacinth roots absorbed only 12% of the gadoterate. When exposed to 5 mg/L of GdCl3, the roots of water hyacinth may effectively remove Gd ions in the aquatic environment, with no visible effect on the general health of the plant. However, the water hyacinth roots did not absorb GBCA. This may result in higher accumulation of Gd in the aqueous environment. The GBCA may be broken down by environmental factors and negatively affect the marine ecosystem.


This study highlights the potential capability of water hyacinths in reducing the increasing gadolinium in the environment, which may be of value in optimizing the phytoremediation of medical waste.


Assuntos
Eichhornia , Poluentes Químicos da Água , Biodegradação Ambiental , Ecossistema , Gadolínio
6.
J Trace Elem Med Biol ; 62: 126653, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32998101

RESUMO

BACKGROUND: Radiotherapy is one of the most important and common therapies for cancer patients. Selenium has been shown to be capable of reducing the side effects of radiotherapy because selenoproteins have anti-oxidative functions against reactive oxygen species that are induced by the radiation. They also function in DNA-repair and cytokine control. PURPOSE: We explored the benefits and risks of selenium supplementation in radiotherapy in our previous review to establish guidelines. In the current study, we expanded the search to cover recent advances in clinical studies of selenium supplementation in radiotherapy. METHODS: We conducted an initial screening in the PubMed using the MeSH terms and keywords "selenium", "radiation", "therapy", and "radiotherapy" using the same methodology applied in our previous review. We identified 121 articles published between January 2013 and December 2019. We then identified eight articles (six studies) on selenium and radiotherapy by excluding 113 articles. RESULTS: In selenium supplementation studies, selenium doses of 300-500 µg/day with duration of 10 days to 6 months were used. Selenium supplementation improved the selenium nutritional conditions of the patients and reduced the side effects of radiotherapy. Selenium supplementation did not reduce the effectiveness of radiotherapy, and no toxicities were reported. CONCLUSION: The results of our previous and current reviews showed that selenium supplementation offers specific benefits for several cancer types treated with radiotherapy. Here, we suggest a new guideline for selenium supplementation in radiotherapy. We recommend determining the selenium status of the patients before radiotherapy, and in cases of deficiency (<100 µg/L serum selenium level), selenium supplement can be beneficial.


Assuntos
Radioterapia/métodos , Selênio/uso terapêutico , Animais , Humanos
7.
Environ Res ; 188: 109776, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32592939

RESUMO

The developing brain is known to be sensitive to the toxic effects of methylmercury (MeHg). The effects of toxic levels of MeHg exposure during the most seemingly vulnerable window of the cerebrum are not well studied. In this study, we aimed to examine the specific effects of toxic levels of MeHg on neurobehavior, neurodegeneration, and selenoenzyme activity in the cerebrum of infant rats. Male Wistar rats (n = 8/group) were orally treated with MeHg at an acute toxic dose (8 mg Hg/kg/day) for 10 consecutive days starting on postnatal day 14 (P14). The MeHg-exposed rats showed a significant reduction in body weight after day 8 and severe neurological symptoms similar to dystonia on day 12 (P25). Motor coordination deficits determined using the rotarod performance test and short-term memory impairment determined using the Y-maze task were observed in the MeHg-exposed rats on day 11 (P24). The MeHg-exposed rats sacrificed on day 12 showed severe cerebral neuronal degeneration, reactive astrocytosis, and TUNEL-positive apoptotic nuclei, with the cerebral Hg concentration of 15.0 ± 1.6 µg/g. Furthermore, the activities of glutathione peroxidase and thioredoxin reductase in the cerebrum in MeHg-exposed rats were lower than those in control. These results indicate that MeHg exposure to infant rats will be useful to predict the effects of MeHg at the cerebral growth spurt in humans.


Assuntos
Cérebro , Mercúrio , Compostos de Metilmercúrio , Animais , Encéfalo , Masculino , Compostos de Metilmercúrio/toxicidade , Ratos , Ratos Wistar
8.
Tohoku J Exp Med ; 249(2): 101-111, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31645522

RESUMO

For the prevention of suicides, the early detection of depression symptoms and the implementation of suicide prevention measures based on the local community's conditions are critical. In rural or remote communities with poor access to urban areas, the medical care is often insufficient. We conducted the present study to investigate the relationship between depressive state and social-environmental factors in a depopulated inland rural area in central Japan, where the suicide rate is high and specialized psychiatric care is not available. Using a correspondence analysis, logistic regression analysis, and structural equation modeling (SEM), we examined the questionnaire responses of 912 residents (average 60.5 years old). Total Health Index-Depression (THI-D) scale scores were used to measure depressive state. The lifestyle-related factor with the strongest link to depressive state was 'concerns about interpersonal relationships' (OR = 2.7, 95% CI: 2.06-3.53, p < 0.0001), whereas financial concerns, number of friends, exercise habits, and perceived amount of sleep were also useful for predicting depressive state. The SEM showed that one's job and private life, particularly concerns about interpersonal relationships, are correlated with higher THI-D scores. Thus, social and lifestyle factors (e.g., concerns about interpersonal relationships and financial situation) can be used to predict depressive state in a depopulated rural area, and the newly revealed order in which depressive symptoms manifest is important. Our findings can be used to advance assessments of depressive symptoms and will be useful for mental health and suicide prevention.


Assuntos
Depressão/epidemiologia , Depressão/psicologia , Estilo de Vida , Características de Residência , População Rural , Adulto , Idoso , Idoso de 80 Anos ou mais , Intervalos de Confiança , Estudos Transversais , Feminino , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Razão de Chances , Inquéritos e Questionários
9.
Br J Radiol ; 92(1099): 20190062, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31045442

RESUMO

OBJECTIVE: To investigate the role of transporter proteins in gadolinium (Gd) distribution and retention in the brain after one high-dose injection of Gd-based contrast agent (GBCA). METHODS AND MATERIALS: 30 ddY mice were randomly divided into three treatment groups to be intravenously injected with either Gadodiamide (linear GBCA), Gadobutrol (macrocyclic GBCA), or Gadoterate (macrocyclic GBCA) at a dose of 5 mmol/kg, while five mice in the control group received 250 µL saline. Five minutes (5 min) and ten days (10d) post-injection, the cerebrospinal fluid (CSF), choroid plexus (CP), and meninges and associated vasculature (MAV) were collected. The brain was then dissected to obtain the olfactory bulb, cerebral cortex, hippocampus, cerebellum, and brainstem. Proteins were extracted and separated by a size-exclusion high-performance liquid chromatography (SEC) system, and Gd concentrations were quantified by inductively coupled plasma mass spectrometry (ICP-MS). RESULTS: 5 m post-injection, the Gadodiamide group had the highest Gd concentration, while Gadoterate had the lowest Gd concentration in all parts of the brain (p < .05). Gd concentration was highest in the cerebrospinal fluid (CSF) of the Gadodiamide group (578.4 ± 135.3 nmol), while Gd concentration was highest in MAV in the Gadobutrol group (379.7 ± 75.4 nmol) at 5 min post-injection. At 10d, in spite of the significant decrease of Gd from all GBCAs ( p < 0.01), retained Gd from Gadodiamide was detected all over the brain in several molecules that varied in size. Gd from Gadobutrol detected in the olfactory bulb (8.7 ± 4.5 nmol) was significantly higher than in other parts of the brain. Although most Gd from Gadobutrol was found in molecules similar in size to Gadobutrol, it was also found in several protein molecules of molecular size larger than the contrast agents. Only a small amount of Gd from Gadoterate was found in the brain. CONCLUSION: GBCAs may be able to pass through intact brain barriers, and the chemical structures of GBCAs may affect the penetration capability of Gd into the brain. Retained Gd in the brain tissue from Gadodiamide and Gadobutrol may be bound to some organic molecules, including proteins. ADVANCES IN KNOWLEDGE: Intact GBCA are able to penetrate a series of brain barrier immediately after administration regardless the type of the chelate. Gd may be bound with macromolecules that may cause Gd retention in the brain.


Assuntos
Encéfalo/metabolismo , Cromatografia em Gel/métodos , Meios de Contraste/farmacocinética , Gadolínio DTPA/farmacocinética , Compostos Heterocíclicos/farmacocinética , Compostos Organometálicos/farmacocinética , Animais , Estudos de Avaliação como Assunto , Gadolínio , Camundongos , Modelos Animais , Solução Salina/administração & dosagem
10.
Environ Health Prev Med ; 24(1): 35, 2019 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-31101007

RESUMO

BACKGROUND: The effects of prenatal exposure to toxic elements on birth outcomes and child development have been an area of concern. This study aimed to assess the profile of prenatal exposure to toxic elements, arsenic (As), bismuth (Bi), cadmium (Cd), mercury (total mercury (THg), methylmercury (MHg), inorganic mercury (IHg)), lead (Pb), antimony (Sb) and tin (Sn), and essential trace elements, copper (Cu), selenium (Se) and zinc (Zn), using the maternal blood, cord blood and placenta in the Tohoku Study of Child Development of Japan (N = 594-650). METHODS: Inductively coupled plasma mass spectrometry was used to determine the concentrations of these elements (except mercury). Levels of THg and MeHg were measured using cold vapour atomic absorption spectrophotometry and a gas chromatograph-electron capture detector, respectively. RESULTS: Median concentrations (25th-75th) of As, Cd, Pb, Sb, Sn and THg in the maternal blood were 4.06 (2.68-6.81), 1.18 (0.74-1.79), 10.8 (8.65-13.5), 0.2 (0.06-0.40) and 0.2 (0.1-0.38) ng mL-1 and 5.42 (3.89-7.59) ng g-1, respectively. Median concentrations (25th-75th) of As, Cd, Pb, Sb, Sn and THg in the cord blood were 3.68 (2.58-5.25), 0.53 (0.10-1.25), 9.89 (8.02-12.5), 0.39 (0.06-0.92) and 0.2 (0.2-0.38) ng mL-1 and 9.96 (7.05-13.8) ng g-1, respectively. CONCLUSIONS: THg and Sb levels in the cord blood were twofold higher than those in the maternal blood. Cord blood to maternal blood ratios for As, Cd and Sb widely varied between individuals. To understand the effects of prenatal exposure, further research regarding the variations of placental transfer of elements is necessary.


Assuntos
Sangue Fetal/química , Exposição Materna/estatística & dados numéricos , Metais/sangue , Placenta/química , Gravidez/sangue , Oligoelementos/sangue , Adulto , Feminino , Humanos , Japão , Troca Materno-Fetal , Saúde da População Urbana
11.
Int J Health Plann Manage ; 34(1): e314-e326, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30188588

RESUMO

Nearly half of the countries in the world are in the process of reforming and strengthening their health care systems. More recently, even low-income and middle-income countries such as Mongolia have focused increasing attention on achieving universal health coverage (UHC). At this critical point, it is necessary to track recent progress and adjust health care strategies and planning. Therefore, this study analyzed changes in the health sector toward achieving UHC based on relevant literature, government documents, and framework analysis. We also investigated how basic principles of UHC were incorporated and reflected in Mongolia's Health Sector Strategic Master Plan. This study clarified the achievements of and challenges facing the health sector that remain or emerged during the plan's implementation over the last decade. Furthermore, all of the reviewed Master Plan strategies were underpinned by basic principles of UHC. However, strategies set out in the next Master Plan will require adjustments and innovative measures to respond to current challenges. This study may be used as a reference for other developing countries to track UHC achievements and serve as a guide to establishing a nation-wide strategic plan.


Assuntos
Atenção à Saúde/organização & administração , Planejamento em Saúde/organização & administração , Cobertura Universal do Seguro de Saúde , Financiamento da Assistência à Saúde , Mongólia , Qualidade da Assistência à Saúde , Desenvolvimento de Pessoal
12.
Biol Trace Elem Res ; 181(1): 71-81, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28429286

RESUMO

Oxidative stress in obesity leads to insulin resistance in type 2 diabetes. Some selenoproteins possess antioxidant properties, suggesting that selenium (Se) may protect against type 2 diabetes; however, evidence from epidemiological studies is contradictory. We hypothesized that Se status before supplementation (baseline) contributes to the supplementation outcome. This study aimed to clarify the influence of baseline Se status on the effect of Se supplementation on the diabetic condition. Six-week-old KKAy mice were fed a diet without supplemental Se or with 0.1 ppm Se in the form of L-selenomethionine (SeM) for 2 weeks to create low-Se and sufficient-Se baseline statuses, respectively. For the next 4 weeks, low-Se mice were given a SeM (0.5 ppm Se)-supplemented diet, and sufficient-Se mice were given either a SeM (0.5 ppm Se)- or sodium selenite (0.5 ppm Se)-supplemented diet; control groups continued on baseline diets. Serum Se concentrations, glutathione peroxidase (GPx) activities, adiponectin levels, glucose tolerance, and insulin sensitivity were analyzed. All mice became diabetic during the 2-week baseline induction period. At the end of the supplementation period, Se-receiving groups demonstrated significantly higher Se concentrations and GPx activities than their respective controls. Sufficient-Se mice receiving SeM had lower blood glucose levels and better insulin sensitivity than control and sodium selenite-receiving mice, whereas low-Se mice receiving SeM showed no such improvements compared with their controls. Our results suggest that Se supplementation in the form of SeM may help prevent type 2 diabetes aggravation in people taking the 55 µg/day Se recommended dietary allowance.


Assuntos
Diabetes Mellitus Tipo 2/prevenção & controle , Suplementos Nutricionais , Selênio/análise , Selenometionina/farmacologia , Animais , Diabetes Mellitus Tipo 2/patologia , Masculino , Camundongos , Camundongos Endogâmicos , Selenometionina/administração & dosagem
13.
Invest Radiol ; 53(2): 110-118, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-28915162

RESUMO

OBJECTIVES: The aim of this study was to examine the effects of perinatal exposure to gadolinium (Gd)-based contrast agents (GBCAs) on the behavior of adulthood offspring. MATERIALS AND METHODS: Pregnant Balb/C mice (n = 5 per group) were intravenously injected with gadoterate meglumine (Magnescope, macrocyclic GBCA), gadodiamide (Omniscan, linear GBCA), or vehicle from pregnancy day 15 to 19, corresponding to embryonic day 15 to 19 of the fetus, at 2 mmol/kg body weight per day. Brain samples from dams and pups were collected on postpartum day 28. The total Gd concentration was quantified by inductively coupled plasma-mass spectrometry (dams, n = 3; gadoterate meglumine-treated pups group, n = 9; and gadodiamide-treated pups group, n = 10). Behavioral testing of offspring was started on postpartum day 70 (control group, n = 22; gadoterate meglumine-treated group, n = 23; and gadodiamide-treated group, n = 20). RESULTS: Higher levels of Gd retention were observed in dams and pups in the gadodiamide-treated group. Perinatal exposure to GBCAs caused anxiety-like behavior, disrupted motor coordination, impaired memory function, stimulated tactile sensitivity, and decreased muscle strength, particularly in the gadodiamide-treated group. CONCLUSIONS: In the present study, we showed that Gd was transferred to pups and was retained in their brain during postnatal development. Gadolinium retention may lead to impaired brain development. These findings indicate that the use of GBCAs in pregnant women should be avoided because it may have adverse effects on the fetus, particularly on brain development.


Assuntos
Comportamento Animal/efeitos dos fármacos , Meios de Contraste/farmacologia , Gadolínio DTPA/farmacologia , Gadolínio/farmacologia , Meglumina/farmacologia , Compostos Organometálicos/farmacologia , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Animais , Encéfalo/efeitos dos fármacos , Meios de Contraste/administração & dosagem , Meios de Contraste/efeitos adversos , Modelos Animais de Doenças , Feminino , Gadolínio/efeitos adversos , Gadolínio DTPA/efeitos adversos , Humanos , Masculino , Meglumina/efeitos adversos , Camundongos , Camundongos Endogâmicos BALB C , Compostos Organometálicos/efeitos adversos , Gravidez , Espectrofotometria Atômica
14.
Jpn J Radiol ; 35(10): 568-573, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28730467

RESUMO

PURPOSE: To investigate the effect of pregnancy and type of gadolinium (Gd)-based contrast agents (GBCAs) on organ retention of Gd in mother and pup mice after maternal administration. MATERIALS AND METHODS: Gd-DTPA-BMA (gadodiamide) or Gd-DOTA (gadoterate dimeglumine) was administered (2.0 mmol/kg of maternal weight) four times to pregnant Balb/c mice from gestational day 16-19, respectively. At 28 days after birth, they were euthanized and their organs (blood, brain, liver, kidney, spleen, and bone) were removed for the measurement of Gd by inductively coupled plasma mass spectrometry. RESULTS: Gd retention in maternal organs was generally lower than that in the organs of non-pregnant mice in both Gd-DTPA-BMA and Gd-DOTA groups. Significantly higher Gd retention was observed in the organs of pups whose mothers were administered Gd-DTPA-BMA as compared to those whose mothers were administered Gd-DOTA. Tissue-to-muscle ratio in the brains of pups was higher than that of mothers. CONCLUSION: We demonstrated in utero transplacental Gd retention in pups. In various organs in both mothers and pups, Gd retention was consistently higher for Gd-DTPA-BMA than Gd-DOTA administration. Pregnancy affected Gd retention in many maternal organs.


Assuntos
Meios de Contraste/farmacocinética , Gadolínio DTPA/farmacocinética , Compostos Heterocíclicos/farmacocinética , Troca Materno-Fetal/fisiologia , Compostos Organometálicos/farmacocinética , Animais , Animais Recém-Nascidos , Sangue/metabolismo , Osso e Ossos/metabolismo , Encéfalo/metabolismo , Feminino , Rim/metabolismo , Fígado/metabolismo , Camundongos , Modelos Animais , Mães , Especificidade de Órgãos , Gravidez , Espectrofotometria Atômica , Baço/metabolismo , Distribuição Tecidual
15.
Oncol Lett ; 13(1): 449-454, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28123581

RESUMO

The administration of radioprotective compounds is one approach to preventing radiation damage in non-cancerous tissues. Therefore, radioprotective compounds are crucial in clinical radiotherapy. Selenium is a radioprotective compound that has been used in previous clinical studies of radiotherapy. However, evidence regarding the effectiveness of selenium in radiotherapy and the mechanisms underlying the selenium-induced reduction of the side effects of radiotherapy remains insufficient. To further investigate the effectiveness of selenium in radiotherapy, the present study examined the protective effects of sodium selenite supplementation administered prior to X-ray radiation treatment in CHEK-1 non-cancerous human esophageal cells. Sodium selenite supplementation increased glutathione peroxidase 1 (GPx-1) activity in a dose- and time-dependent manner. The sodium selenite dose that induced the highest GPx-1 activity was determined to be 50 nM for 72 h prior to radiotherapy. The half-maximal inhibitory concentration of sodium selenite in CHEK-1 cells was 3.6 µM. Sodium selenite supplementation increased the survival rate of the cells in a dose-dependent manner and enhanced the degree of cell viability at 72 h post-irradiation (P<0.05). Combined treatment with 50 nM sodium selenite and 2 gray (Gy) X-ray irradiation decreased the number of sub-G1 cells from 5.9 to 4.2% (P<0.05) and increased the proportion of G1 cells from 58.8 to 62.1%, compared with 2 Gy X-ray irradiation alone; however, this difference was not statistically significant (P=1.00). Western blot analysis revealed that treatment with 2 Gy X-ray irradiation significantly increased the expression levels of cleaved poly (ADP-ribose) polymerase (PARP; P<0.05). In addition, combined treatment with 50 nM sodium selenite and 2 Gy X-ray irradiation reduced the expression levels of cleaved PARP protein, compared with 2 Gy X-ray irradiation alone; however, this reduction was not statistically significant (P=0.423). These results suggest that 50 nM sodium selenite supplementation administered for 72 h prior to irradiation may protect CHEK-1 cells from irradiation-induced damage by inhibiting irradiation-induced apoptosis. Therefore, sodium selenite is a potential radioprotective compound for non-cancerous cells in clinical radiotherapy.

16.
Artigo em Inglês | MEDLINE | ID: mdl-27617003

RESUMO

Gadolinium (Gd)-based contrast agents (GBCAs) are used in diagnostic imaging to enhance the quality of magnetic resonance imaging or angiography. After intravenous injection, GBCAs can accumulate in the brain. Thyroid hormones (THs) are critical for the development and functional maintenance of the central nervous system. TH actions in brain are mainly exerted through nuclear TH receptors (TRs). We examined the effects of GBCAs on TR-mediated transcription in CV-1 cells using transient transfection-based reporter assay and TH-mediated cerebellar Purkinje cell morphogenesis in primary culture. We also measured the cellular accumulation and viability of Gd after representative GBCA treatments in cultured CV-1 cells. Both linear (Gd-diethylene triamine pentaacetic acid-bis methyl acid, Gd-DTPA-BMA) and macrocyclic (Gd-tetraazacyclododecane tetraacetic acid, Gd-DOTA) GBCAs were accumulated without inducing cell death in CV-1 cells. By contrast, Gd chloride (GdCl3) treatment induced approximately 100 times higher Gd accumulation and significantly reduced the number of cells. Low doses of Gd-DTPA-BMA (10(-8) to 10(-6)M) augmented TR-mediated transcription, but the transcription was suppressed at higher dose (10(-5) to 10(-4)M), with decreased ß-galactosidase activity indicating cellular toxicity. TR-mediated transcription was not altered by Gd-DOTA or GdCl3, but the latter induced a significant reduction in ß-galactosidase activity at high doses, indicating cellular toxicity. In cerebellar cultures, the dendrite arborization of Purkinje cells induced by 10(-9)M T4 was augmented by low-dose Gd-DTPA-BMA (10(-7)M) but was suppressed by higher dose (10(-5)M). Such augmentation by low-dose Gd-DTPA-BMA was not observed with 10(-9)M T3, probably because of the greater dendrite arborization by T3; however, the arborization by T3 was suppressed by a higher dose of Gd-DTPA-BMA (10(-5)M) as seen in T4 treatment. The effect of Gd-DOTA on dendrite arborization was much weaker than that of the other compounds. These results indicate that exposure to specific GBCAs may, at least in part, cause toxic effects in the brain by disrupting the action of THs on TRs. The toxic effects of GBCAs may depend on the chemical structure of GBCA and the dose. Thus, it is very important to choose appropriate GBCAs for imaging to prevent adverse side effects.

17.
Br J Radiol ; 89(1066): 20160509, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27459250

RESUMO

OBJECTIVE: To investigate the distribution and clearance of retained gadolinium (Gd) in various parts of the brain after intravenously administering a Gd-based contrast agent (GBCA) in normal and renal failure mouse models. METHODS: Two different mouse models: normal (n = 12) and renal failure (n = 12) were used. Clinical GBCAs (Gd-DTPA-BMA, 5 mmol kg(-1), or Gd-DOTA, 5 mmol kg(-1)) were intravenously administered five times per week for 4 weeks. Both groups were divided into two subgroups based on the time point for sample collection: 3 days (3d) and 45 days (45d) after the last injection. Normal saline (5 ml kg(-1)) was intravenously administered to mice of the control groups in the same manner. Samples of the following parts of the mouse brain were obtained on dissection: olfactory bulb, cerebral cortex, hippocampus, thalamus, mid-brain, cerebellum, pons and medulla. (158)Gd concentrations in each sample were quantified using inductively coupled plasma mass spectrometry. RESULTS: The olfactory bulb had the highest Gd concentration in both Gd-DTPA-BMA and Gd-DOTA groups. Gd retention was higher in the Gd-DTPA-BMA group than in the Gd-DOTA group (p < 0.01). In the Gd-DTPA-BMA group, Gd retention in the 3d subgroups of normal and renal failure models were similar (p = 0.4). At 45d, Gd in the Gd-DTPA-BMA group was not eliminated from the renal failure model (p = 0.1), while that in the Gd-DOTA group was eliminated from both the normal and renal failure mouse models (p < 0.01). CONCLUSION: Gd distributions in the brain for both groups were similar, regardless of the renal function and GBCA type. The Gd concentration was highest in the olfactory bulb of both groups. In the Gd-DOTA group, Gd was eliminated from the brain in both mouse models, while in the Gd-DTPA-BMA group, Gd clearance was limited. ADVANCES IN KNOWLEDGE: Gd concentration in the brain was not affected by renal function. The clearance of Gd from linear GBCA was limited in both the normal and impaired renal function mouse models.


Assuntos
Encéfalo/metabolismo , Meios de Contraste/farmacocinética , Gadolínio DTPA/farmacocinética , Compostos Heterocíclicos/farmacocinética , Compostos Organometálicos/farmacocinética , Animais , Modelos Animais de Doenças , Feminino , Camundongos , Insuficiência Renal/metabolismo , Espectrofotometria Atômica
18.
Southeast Asian J Trop Med Public Health ; 47(2): 299-308, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27244968

RESUMO

Selenium deficient areas have been associated with a higher prevalence of cardiovascular disease in some countries. In this study, we investigated the correlation between cardiovascular disease prevalence and selenium concentration in paddy soil and rice grains, the main staple food in Lampung, Indonesia. Paddy soil and rice samples (n(s) = 35) from eight regencies (n(d) = 8) in Lampung were analyzed for selenium content. The prevalences of heart disease, stroke, and hypertension in those regencies were obtained from the Ministry of Health of Indonesia. The Shapiro-Wilk's test was used to examine the data distribution. The Pearson's correlation was used to examine the correlation between cardiovascular disease prevalence and selenium concentration in the paddy soil and rice grains. Heart disease prevalence was negatively correlated with the selenium concentration in the paddy soil (r = -0.77, p = 0.02) and rice grain (r = -0.71, p = 0.05). A negative correlation was seen for stroke prevalence and selenium concentration in paddy soil (r = -0.76, p = 0.02). Hypertension prevalence was negatively correlated with the selenium concentration in the rice grains (r = -0.83, p = 0.01). These findings suggest that the selenium concentration in paddy soil and rice grains in the Lampung area may play a role in the fact the area has the lowest cardiovascular disease prevalence in Indonesia. Keywords: selenium, cardiovascular diseases, paddy soil, rice grain, Indonesia


Assuntos
Doenças Cardiovasculares/epidemiologia , Oryza/química , Selênio/análise , Solo/química , Oligoelementos/análise , Grão Comestível , Humanos , Indonésia/epidemiologia , Poluentes do Solo/análise
19.
Invest Radiol ; 51(10): 655-60, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27299580

RESUMO

OBJECTIVES: The aim of this study was to investigate the impact of impaired renal function on gadolinium (Gd) retention in various organs after Gd-based contrast agent injection. MATERIALS AND METHODS: After local animal care and review committee approval, 23 normal mice and 26 with renal failure were divided into 4 treatment groups (Gd-DTPA-BMA, 5 mmol/kg; Gd-DOTA, 5 mmol/kg; GdCl3, 0.02 mmol/kg; and saline, 250 µL). Each agent was intravenously administered on weekdays for 4 weeks. Samples were collected on days 3 (short-term) and 45 (long-term) after the last injection. Gadolinium concentrations were quantified by inductively coupled plasma-mass spectrometry. RESULTS: Three mice with renal failure and 2 normal mice in the GdCl3 group and 1 mouse with renal failure in the Gd-DTPA-BMA group died. In the Gd-DTPA-BMA group, impaired renal function increased short-term Gd retention in the liver, bone, spleen, skin, and kidney (P < 0.01) but did not affect long-term Gd retention. Gd-DTPA-BMA showed higher Gd retention than Gd-DOTA. Although Gd retention in the Gd-DOTA group was generally low, impaired renal function increased only long-term hepatic Gd retention. Hepatic and splenic Gd retentions were significantly higher than other organs' Gd retention in the GdCl3 group (P < 0.01). Renal function did not affect brain Gd retention, regardless of the Gd compound used. CONCLUSIONS: The tendency of Gd retention varied according to the agent, regardless of renal function. Although renal impairment increased short-term Gd retention after Gd-DTPA-BMA administration, long-term Gd retention for Gd-based contrast agents was almost unaffected by renal function, suggesting that the chemical structures of retained Gd may not be consistent and some Gd is slowly eliminated after initially being retained.


Assuntos
Meios de Contraste/metabolismo , Gadolínio/metabolismo , Rim/fisiopatologia , Insuficiência Renal/fisiopatologia , Animais , Modelos Animais de Doenças , Feminino , Espectrometria de Massas , Camundongos
20.
BMC Public Health ; 16: 69, 2016 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-26801622

RESUMO

BACKGROUND: Posyandu, or pos pelayanan terpadu (integrated service post), is a community-based activity for health services in Indonesia. According to the Indonesian Basic Health Survey, the prevalence of children under five in Indonesia who suffered from being underweight was 19.6 %. The wasting was 12.1 % and the stunting was 37.2 % in 2013, and these values have not changed greatly from 2007; much greater than the WHO targets of, less than 10 % underweight, 5 % wasting, and 20 % stunting. In Aceh were 26.6, 16.8, and 43.3 %, respectively. Also, the participation percentages of mothers to Posyandu was about 45 %, far below the national target of 100 %. In Aceh Province, the percentage was even lower (34 % in 2013). This study aimed to investigate the factors influencing participation of mothers in Posyandu. METHODS: This research used a cross-sectional design with sample of mothers who had children under five. They were chosen by multistage random sampling. Sample size was determined by the WHO formula. Face-to-face interviews were carried out using a questionnaire. The questionnaire consisted of items about socio-demographic characteristics, satisfaction with Posyandu services, attitude towards Posyandu benefits, and intention to attend Posyandu. The collected data were analyzed by using EZR (version 1.21). Fisher's exact test was performed to examine the associations between the socio-demographic factors, attitude, satisfaction, and intention covariates with participation. Logistic regression was used to describe the strength of the relationship between the predictor variables and participation. RESULTS: There were no significant differences in age, marital status, education level, occupation, family size, and distance to Posyandu between low participation group except for the monthly household income. Among the socio-demographic factors, only monthly household income had a significant association with the frequency of mothers' participation. Satisfaction, attitude, and intention were associated with participation. The logistic regression showed that monitoring the nutritional status of children under five was the main reason that mothers participated in Posyandu. Mothers who were satisfied with the Posyandu services were more likely to attend than those who were dissatisfied. Respondents with intention to participate in Posyandu every month were more likely to attend than those who did not intend to attend every month. Households with low income were more likely to participate in Posyandu than households with high income. CONCLUSION: Household income, mothers' satisfaction with Posyandu services, attitude towards Posyandu benefits and intention to attend Posyandu affect the participation frequency of the mother. In addition, monitoring the nutritional status of children under five was the main reason respondents attend Posyandu. Improving the quality of Posyandu services and providing qualified resources are needed to promote mothers' participation.


Assuntos
Transtornos da Nutrição Infantil/prevenção & controle , Serviços de Saúde Comunitária/estatística & dados numéricos , Mães/psicologia , Adulto , Fatores Etários , Atitude , Criança , Pré-Escolar , Comportamento do Consumidor , Estudos Transversais , Feminino , Inquéritos Epidemiológicos , Humanos , Indonésia/epidemiologia , Lactente , Recém-Nascido , Intenção , Entrevistas como Assunto , Pobreza , Prevalência , Fatores Socioeconômicos
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