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The generally nonpolar SrTiO3 has attracted more attention recently because of its possibly induced novel polar states and related paraelectric-ferroelectric phase transitions. By using controlled pulsed laser deposition, high-quality, ultrathin, and strained SrTiO3 layers were obtained. Here, transmission electron microscopy and theoretical simulations have unveiled highly polar states in SrTiO3 films even down to one unit cell at room temperature, which were stabilized in the PbTiO3/SrTiO3/PbTiO3 sandwich structures by in-plane tensile strain and interfacial coupling, as evidenced by large tetragonality (â¼1.05), notable polar ion displacement (0.019 nm), and thus ultrahigh spontaneous polarization (up to â¼50 µC/cm2). These values are nearly comparable to those of the strong ferroelectrics as the PbZrxTi1-xO3 family. Our findings provide an effective and practical approach for integrating large strain states into oxide films and inducing polarization in nonpolar materials, which may broaden the functionality of nonpolar oxides and pave the way for the discovery of new electronic materials.
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OBJECTIVE: To explore the therapeutic effect of transplantation of bone marrow mesenchymal stem cells (BMSCs) over-expressing Cx43 on heart failure in post-infarction rats. METHODS: Sixty SD rats were randomly divided equally into 4 groups: sham group, DMEM/F12 group injected with DMEM/F12, EGFP group with transplanted EGFP transfected BMSCs and Cx43 group with transplanted Cx43 transfected BMSCs. Myocardial infarction model was established by ligating anterior descending branch and the cells were transplanted after 30 minutes. At Week 4 post-infarction, the heart functions of rats were evaluated by echocardiography. After the rats were sacrificed, their tissue samples were collected. The areas of myocardial infarction and the levels of collagen fiber content were measured. And the expressions of EGFR and Cx43 were observed under laser confocal microscopy. The level of Cx43 mRNA was measured by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: As compared with the DMEM/F12 group, cardiac function was improved significantly, myocardial infarct area shrunk and collagen fiber content decreased significantly in the EGFP and group in Cx43 groups the. Survival of BMSCs and the formation of gap junction between BMSCs and the host myocardium could be observed under laser confocal microscopy both in EGFP group and Cx43 groups. And the post-infarction, expression of Cx43 mRNA in myocardial tissue decreased significantly in the group DMEM/F12, when compared with sham group (0.18 ± 0.05 vs 0.78 ± 0.14, P < 0.01). There was no significant difference on expression of Cx43 mRNA between DMEM/F12 group and EGFP group (0.18 ± 0.05 vs 0.20 ± 0.09, P > 0.05). The lever of Cx43 mRNA was higher in group Cx43 than in group DMEM/F12 and group EGFP(0.39 ± 0.14 vs 0.18 ± 0.05, P < 0.01; 0.39 ± 0.14 vs 0.20 ± 0.09, P < 0.05). CONCLUSION: Transplantation of BMSCs attenuates ventricular remodeling and improves cardiac functions. It may result from the over-expression of Cx43 gene through its effects of improving gap junction remodeling and increasing electro-mechanical coupling between myocardial cells in peri-infarct area.
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Conexina 43/metabolismo , Insuficiencia Cardíaca/cirugía , Trasplante de Células Madre Mesenquimatosas , Animales , Células de la Médula Ósea/metabolismo , Uniones Comunicantes/metabolismo , Masculino , Células Madre Mesenquimatosas/metabolismo , Infarto del Miocardio/complicaciones , Infarto del Miocardio/metabolismo , Infarto del Miocardio/cirugía , Ratas , Ratas Sprague-Dawley , TransfecciónRESUMEN
Innovative iron/calcium in-situ-impregnated mesoporous activated carbons (GL100 and GL200) have been prepared by iron/calcium in-situ-impregnation and Multistage Depth-Activation. Arsenic adsorption kinetics, isotherms, thermodynamics, and re-usability were investigated. Effects of surface-absorbed (ST-HA) and dissolved states humic acid (DHA) on the arsenic adsorption were also determined. Results suggested in-situ iron/calcium impregnation caused the well-development of mesoporous structures during ranges of 2.0-5.0 nm in GL100 and 5.0-50 nm in GL200, respectively. The increase of iron/calcium ensured surface basicity and high ash contents on GL100/GL200, and As(III)/As(V) can be better adsorbed in neutral conditions with higher kinetics in comparison with regular mesoporous carbon XHIT. Maximum adsorption capacities of As(III)/As(V) by GL100 and GL200 were 2.985/3.385 mg/g and 2.516/2.807 mg/g, respectively. Arsenic desorption and carbon re-usability of GL100/200 was improved. As(III)(As (V)) adsorption capacities by GL100 and GL200 were 2.437(1.672) mg/g and 1.740(1.308) mg/g, respectively, after eight cycles. Arsenic adsorption capacities on GL100 were proved to be promoted with the presence of low-level of ST-HA or DHA, and be inhibited at a high-level. As(V) was bound more strongly than As(III) in the presence of ST-HA. As(III)/As(V) uptakes increased slightly and decrease gradually to 1.75/1.86 mg/g in the presence of DHA (0-10 mg DOC/L). Physisorption and chemisorption mechanisms dominant in arsenic adsorption on GL100 in presence of humic acid, forming inner-sphere complexation with metallic oxide, functional groups on carbon surface and humic acid structure, or ternary surface complexation via cationic metal ions as cation bridge.
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Arsénico/aislamiento & purificación , Carbón Orgánico/química , Frío , Purificación del Agua/métodos , Adsorción , Arsénico/química , Calcio/química , Sustancias Húmicas/análisis , Hierro/química , Cinética , Contaminantes Químicos del Agua/análisis , Contaminantes Químicos del Agua/aislamiento & purificaciónRESUMEN
Purpose: The aim of the present prospective follow-up study was to explore the early indicators of hypothyroidism and the final changes in thyroid volume in subacute thyroiditis (SAT) patients. Methods: We enrolled 61 SAT patients and followed them up for 2 years to assess the incidence of hypothyroidism and changes in thyroid volume. Binary logistic regression and receiver operating characteristic (ROC) curves were used for data analysis. Results: During the 2 years follow-up period, we found that the volumes of the thyroid gland in SAT patients at 1 and 2 years were significantly smaller than those in the healthy control group, which were significantly smaller compared to the initial thyroid volumes after SAT onset (p < 0.001). Also, the thyroid volumes of SAT patients with hypothyroidism were significantly smaller than those of SAT patients without hypothyroidism. The early maximum thyroid-stimulating hormone (TSH) values (within 3 months after SAT onset) were closely related to the incidence of hypothyroidism at 2 years. The OR value was 1.18 (95% CI = 1.01-1.38, p = 0.032). The early maximum TSH value had a maximum area under the ROC curve (AUC) of 0.866 for the development of hypothyroidism 2 years after SAT onset vs. euthyroidism (p < 0.001). Conclusions: The thyroid volumes of patients increased significantly after the onset of SAT, while during the follow-up these volumes decreased; the thyroid volumes at 1 and 2 years were significantly smaller than those of normal healthy subjects, especially in SAT patients with hypothyroidism. Furthermore, the early maximum TSH value could be used as an effective indicator of the development of hypothyroidism 2 years after the onset of SAT.
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Antiinflamatorios no Esteroideos/efectos adversos , Hipotiroidismo/epidemiología , Tiroiditis Subaguda/tratamiento farmacológico , Tirotropina/metabolismo , Adulto , Biomarcadores/análisis , Estudios de Casos y Controles , Femenino , Estudios de Seguimiento , Humanos , Hipotiroidismo/inducido químicamente , Hipotiroidismo/patología , Masculino , Pronóstico , Estudios Prospectivos , Pruebas de Función de la Tiroides , Tiroiditis Subaguda/metabolismo , Tiroiditis Subaguda/patologíaRESUMEN
OBJECTIVE: To determine the factors that influence the development of abnormal thyrotropin (TSH) level in an euthyroid population. METHODS: We conducted a follow-up study in 3 communities with different iodine status. Of the 3403 euthyroid subjects at baseline screened in 1999, 80.1% (n = 2727) was visited and sampled in 2004 for measuring TSH, thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TgAb). RESULTS: Iodine status in the 3 communities were stable. Decreased TSH level (< 0.3 mU/L) developed in 2.5% (n = 68) of sampled subjects, while raised TSH level (> 4.8 mU/L) in 2.4% (n = 64). A logistic analysis showed that risk factors for developing decreased TSH level included positive conversion of TPOAb (OR = 5.5), positive TPOAb both in 1999 and in 2004 (OR = 4.0), positive TgAb in 2004 (OR = 3.7) and TSH < 1.0 mU/L in 1999 (OR = 2.6). Risk factors involved in developing raised TSH level included iodine status of Zhangwu community (OR = 4.1), iodine status of Huanghua community (OR = 3.9), positive TgAb in 2004 (OR = 3.7), positive TPOAb both in 1999 and 2004 (OR = 3.6), positive conversion of TPOAb (OR = 2.7) and TSH > 1.9 mU/L in 1999 (OR = 2.6). CONCLUSIONS: Exposure to long-term iodine excess imposes danger of developing hypothyroidism. The risk will be even higher when exposing to iodine adequacy after correction of iodine deficiency. An interval between 1.0 and 1.9 mU/L of TSH level was optimal with the least probability of developing abnormal TSH level.
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Yodo/administración & dosificación , Enfermedades de la Tiroides/prevención & control , Tirotropina/sangre , Adulto , Autoanticuerpos/sangre , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Estado Nutricional , Glándula Tiroides/fisiologíaRESUMEN
The difference in the atrial organizational structure between patients with atrial fibrillation (AF) and those with sinus rhythm was investigated. In order to analyze the rationality in explaining the electrocardiogram (ECG) characteristics of AF with statistics data or tissue remodeling model, and the logical relationship between the hypothesis of pulmonary veins (PV) muscle sleeves and that of multi wavelets in mechanism of AF, we examined the expression of collagen volume fraction of type I (CVF-I) with picrosirius red staining, connexin 40 (Cx40) by immunohistochemistry, and intercalated disc (ID) using transmission electron microscope in atrial tissue. The results showed that there was significant difference in the expression of CVF-I (t=3.827, P<0.01), Cx40 (t=4.21, P<0.01), and groups of the ID that keeping the electrical transmission and atrial electrical coupling synchronization (t=15.116, P<0.001), but no significant difference was found in total IDs (t=0.611, P=0.543) between patients with AF and those with sinus rhythm. The quantitative differences in the tissue remodeling could not explain the ECG characteristics of AF. The number of normal IDs and abnormal distribution are the structural basis to trigger and maintain atrial electrical remodeling, and induce and maintain AF. Such histological reconstruction supports the hypothesis of multi wavelets and can also explain ECG features.
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Fibrilación Atrial/metabolismo , Remodelación Atrial/fisiología , Conexinas/genética , Atrios Cardíacos/fisiopatología , Adulto , Anciano , Fibrilación Atrial/diagnóstico por imagen , Fibrilación Atrial/fisiopatología , Remodelación Atrial/genética , Electrocardiografía , Femenino , Corazón/diagnóstico por imagen , Atrios Cardíacos/diagnóstico por imagen , Humanos , Masculino , Microscopía Electrónica de Transmisión , Persona de Mediana Edad , Miocardio/metabolismo , Miocardio/patología , Venas Pulmonares/metabolismo , Venas Pulmonares/patología , Adulto Joven , Proteína alfa-5 de Unión ComunicanteRESUMEN
CONTEXT: Methimazole (MMI) and propylthiouracil (PTU) are widely used as antithyroid drugs (ATDs) for the treatment of Graves' disease. Both MMI and PTU reduce thyroid hormone levels by several mechanisms, including inhibition of thyroid hormone synthesis and secretion. In addition, PTU decreases 5'-deiodination of T(4) in peripheral tissues. ATDs may also interfere with T(3) binding to nuclear thyroid hormone receptors (TRs). However, the effect of ATDs on the transcriptional activities of T(3) mediated by TRs has not been studied. OBJECTIVE: The present study was undertaken to determine whether ATDs have an effect on the gene transcription regulated by T(3) and TRs in vitro. METHODS: Transient gene expression experiments and GH secretion assays were performed. To elucidate possible mechanisms of the antagonistic action of ATDs, the interaction between TR and nuclear cofactors was examined. RESULTS: In the transient gene expression experiments, both MMI and PTU significantly suppressed transcriptional activities mediated by the TR and T(3) in a dose-dependent manner. In mammalian two-hybrid assays, both drugs recruited one of the nuclear corepressors, nuclear receptor corepressor, to the TR in the absence of T(3). In addition, PTU dissociated nuclear coactivators, such as steroid receptor coactivator-1 and glucocorticoid receptor interacting protein-1, from the TR in the presence of T(3). Finally, MMI decreased the GH release that was stimulated by T(3). CONCLUSIONS: ATDs inhibit T(3) action by recruitment of transcriptional corepressors and/or dissociation of coactivators. This is the first report to show that ATDs can modulate T(3) action at the transcriptional level.
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Antitiroideos/farmacología , Receptores de Hormona Tiroidea/antagonistas & inhibidores , Transcripción Genética/efectos de los fármacos , Activación Transcripcional/efectos de los fármacos , Células Cultivadas , Hormona del Crecimiento/genética , Hormona del Crecimiento/metabolismo , Humanos , Metimazol/farmacología , Modelos Biológicos , Propiltiouracilo/farmacología , Proteínas Represoras/metabolismo , Somatotrofos/efectos de los fármacos , Somatotrofos/metabolismo , Transactivadores/metabolismoRESUMEN
OBJECTIVE: This study aimed to investigate the effects of folate on the monocyte chemoattractant protein-1 (MCP-1) expression and release in rats with hyperhomocystinemia induced by ingestion of excess methionine. METHODS AND RESULTS: Thirty male Sprague-Dawley rats (200+/-20 g) were randomly divided into three groups (n=10 for each group): control group (Control), high-homocystinemia (Hhcy) group, and folate treatment (FA) group. They were fed with a normal regular diet, enriched by 1.7% methionine plus 1.7% methionine and 0.006% folate for 45 days. Our study showed the following: (a) A high methionine diet for 45 days is sufficient to induce hyperhomocystinemia; folate supplementation to the rats fed the high-methionine diet prevented an elevation homocysteine (Hcy) levels in the blood (P<.01). (b) Compared with the Control group, the Hhcy group had elevated plasma levels of MCP-1, and Hcy was significantly correlated with MCP-1 (P<.05). (c) The protein and mRNA expression of MCP-1 in the aorta was higher in rats from the Hhcy group than in rats from the Control group. (d) Most important, after folic acid supplementation, the lowering of Hcy levels was accompanied by a marked reduction of MCP-1 expressed in aortae and released from plasma and peripheral blood mononuclear cells (PBMCs) stimulated by oxidized low-density lipoprotein (P<.05, P<.01). CONCLUSION: Folic acid supplementation not only can blunt the rise in Hcy and reduce MCP-1 released from both plasma and PBMCs of rats with hyperhomocystinemia but also can downgrade MCP-1 expression in the aorta of rats with hyperhomocystinemia.
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Aorta/efectos de los fármacos , Quimiocina CCL2/metabolismo , Ácido Fólico/farmacología , Hiperhomocisteinemia/prevención & control , Leucocitos Mononucleares/metabolismo , Complejo Vitamínico B/farmacología , Animales , Aorta/metabolismo , Western Blotting , Células Cultivadas , Quimiocina CCL2/sangre , Quimiocina CCL2/genética , Modelos Animales de Enfermedad , Ácido Fólico/uso terapéutico , Homocisteína/sangre , Hiperhomocisteinemia/inducido químicamente , Hiperhomocisteinemia/metabolismo , Inmunohistoquímica , Leucocitos Mononucleares/efectos de los fármacos , Lipoproteínas LDL/metabolismo , Masculino , Metionina , ARN Mensajero/metabolismo , Ratas , Ratas Sprague-Dawley , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Factores de Tiempo , Complejo Vitamínico B/uso terapéuticoRESUMEN
BACKGROUND: Fibrosis in atrial myocardium is a common phenomenon for patients with atrial fibrillation (AF). Remodeling of connexins was found accompanying with AF. The aim of the study is to investigate whether it is by causing the remodeling of connexin 43 (Cx43) that the fibrosis of atrial muscle plays an important role during the initiation and maintenance of AF. METHODS: Samples of right atrial appendage were taken from 24 patients with rheumatic valvular disease during surgery. Fibrosis and remodeling of Cx43 was examined by microscopy and ultramicroscopy technique and analyzed by image analyzer. The collagen volume fraction of type I (CVF-I) and the volume fraction of Cx43 (Cx43VF) were studied between AF and sinus rhythm (SR) groups. RESULTS: (1) Microscopic examination demonstrated that CVF-I significantly increased and Cx43VF decreased in patients with AF compared to those with SR. (2) The CVF-I was negatively correlated with the Cx43VF. CONCLUSION: The results suggest that fibrosis and remodeling of Cx43 are involved in the pathophysiologic mechanism of human AF. Fibrosis of atrial muscle may play an important role in the process of AF by means of interfering with remodeling of connexins.
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Fibrilación Atrial/patología , Colágeno Tipo I , Conexina 43 , Atrios Cardíacos/patología , Miocardio/patología , Adulto , Fibrilación Atrial/fisiopatología , Colágeno Tipo I/ultraestructura , Conexina 43/ultraestructura , Femenino , Fibrosis , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Immunoglobulin A nephropathy (IgAN) is the most frequent form of glomerulonephritis, which is characterized by glomerular proliferation and renal inflammation. Icariin is a flavonoid from the Chinese herb Epimedium, and its anti-inflammatory effect has been reported. This study aimed to investigate the effects of icariin on the renal damage in IgAN rats and the mechanisms behind these effects. IgAN model was established in Sprague-Dawley rats by oral and intravenous immunization with bovine gamma-globulin for 12 weeks, and rats were treated with icariin from 12 to 18 weeks. At the end of experimental period, kidneys, urine, and blood samples were collected for further analysis. Our results showed that icariin ameliorated the increase in the levels of proteinuria, serum creatinine, and urea nitrogen without severe side effects. IgAN rats exhibited significantly increased IgA deposition, mesangial matrix expansion, and glomerular fibrosis, while icariin treatment markedly attenuated these alterations. Moreover, treatment with icariin also dramatically blocked nuclear factor kappa b (NF-κB) nuclear translocation and Nlrp3 inflammasome activation in IgAN rats, leading to reduced downstream proinflammatory cytokines production. Mechanistically, we found that icariin treatment inhibited IKKß and IκBα phosphorylation and IκBα degradation in IgAN rats. Our data demonstrate that icariin ameliorates renal damage in IgAN rats via inhibition of NF-κB-mediated Nlrp3 inflammasome activation. These findings provide insight into an application of icariin for the treatment of IgAN disease, and represent a novel mechanism behind these effects.
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To investigate effects of supplementation of folic acid on the expression of adhesion molecules VCAM-1 in the aortas of rats with hyperhomocysteinemia. Thirty male SD rats (200 +/- 20 g) were invided into 3 groups (n = 10 for each group): control group(Control), high Met group(Met) and Met plus Folate group(Met + Folate), fed. for 45 days. Plasma Hcy levels were higher with the high-methionine diet (140.68 +/- 36.87 micromol/L vs 6.47 +/- 1.10 micromol/L in control rats) an effect which was reduced by folate. Respectively, the aortic expression of adhesion molecules VCAM-1 at protein and mRNA levels were higher in the Met groups than those in the control groups or the Met + Folate groups. A high methionine diet for 45 days was sufficient to induce hyperhomocysteinemia. Folate supplementation prevented elevation of Hcy levels in the blood, and reduced expression of the adhesion molecule VCAM-1. Hyperhomocysteinemia is now regarded as one of the important risk factors for cardiovascular and cerebralvascular disorders.[Welch GN, Loscalzo J. Homocysteine and atherothrombosis. N Engl J Med 1998; 38(15):1042-50.] Several plausible mechanisms for Hcy-induecd atherosclerosis have been proposed. These include endothelial dysfunction, enhancement of oxidative stress, reduction in NO bioavailability, and augmentation of thrombus formation.[Holven KB, Holm T, Aukrust P, et al. Effect of folic acid treatment on endothelium-dependent vasodilation and nitric oxide-derived end products in hyperhomocysteinemic subjects . Am J Med 2001;110(7):536-42; Guba SC, Fonseca V, Fink LM. Hyperhomocysteinemia and thrombosis. Semin Thromb Hemost 1999;25(3):291-309.] However, the precise molecular mechanism is still unclear. Recent reports have suggested a role for inflammatory processes in the pathogenesis of atherosclerosis.[Gerard C, Rollins BJ. Chemokines and disease. Nat Immunol 2001;2(2):108-15.] Dysfunction of endothelial cells is the key process promoting inflammatory reactions. On injury, endothlial cells are capable of producing various cytokines that participate in inflammatory reactions in the arterial wall. Although results from in vitro studies suggest that Hcy, at pathophysiological concentrations, stimulates chemokine expression in vascular cells, it is unknown whether hyperhomocysteinemia can initiate similar changes, leading to enhanced momocyte adhesion/binding to the vascular endothelium in vivo.[Zeng X, Dai J, Remick DG, Wang X. Homocysteine mediated expression and secretion of monocyte chemoattractant protein-1 and interleukin-8 in human monocytes. Circ Res 2003;93(4):311-20.] On the basis of the potential pathogenic role of chemokines in atherogenesis, the objective of the present study was to investigate that homocsteine may exert its effect in part though adhesion molecules VCAM-1 and that folic acid supplementation may downregulate these inflammatory responses. Male Sprague-Dawley rats (bred from animal centers of Tongji Medical College, Huazhong Science and Technology University) aged 8 weeks were divided into 3 groups(n=10 for each group) and maintained for 45 days on the following diets before the experiments: (1) regular diet; (2) high-metheionine diet, consisting of regular diet plus 1.7% methionine; and (3) high-methionine plus folate -rich diet, consisting of regular diet plus 1.7% methionine and 0.006% folate.[Boisvert WA, Curtiss LK, Terkeltaub RA. Interleukin-8 and its receptor CXCR2 in atherosclerosis. Immunol Res 2000;21(2-3):129-d37.] Plasma and serum samples wee colleced and stored at -80 degrees C after 45 days until analysis. The plasma homocysteine concentration of rats in three groups were determined by high-pressue liquid chromatography. To detect the endothelial expression of adhesion molecules VCAM-1, the thoracic aorta was isolated and dived into segments. These segments were immersion-fixed in 10% neutral-buffered formalin overlight and then embedded in paraffin. Sequential 5 mum paraffin-embedded cross sections were prepared. Immunohistochemical analyisis was performed to detect vascular cell adhesion molecule(VCAM)-1, The fixed cryosections were immediately blcked in 10% horse serum and phosphate baffered saline(PBS) at room temperature for 30 min. Goat polyclonal andibodies against rat VCAM-1(Santa Cruz Biotechnology) were diluted 1:100 in PBS and incubated with the cryosections for 1 h of room temperature. After three washes, the sections were incubated with biotin-conjugated rabbit anti-goat immunoglobulins(Dako) at 1:250 dilution in PBS. After three washes, the samples were mounted in 90% glycerol-PBS. Photographs were taken by use of a light microscope at a mignification of x200.
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Aorta/metabolismo , Ácido Fólico/farmacología , Hiperhomocisteinemia/metabolismo , Molécula 1 de Adhesión Celular Vascular/biosíntesis , Animales , Masculino , ARN Mensajero/metabolismo , Ratas , Ratas Sprague-DawleyRESUMEN
OBJECTIVE: To investigate the relationship of thyroid autoantibodies including serum thyroid stimulating antibody (TSAb), thyroid stimulation blocking antibody (TSBAb) and iodine intake with the development and prognosis of Graves' hyperthyroidism. METHODS: A total of 63 subjects with overt hyperthyroidism were screened out from 3 Chinese rural communities with different iodine intakes at first survey. Serum TSAb, TSBAb, thyrotropin binding inhibitory immunoglobulin (TBII), thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TGAb) were detected. The patients were followed up 2 years later. TSAb and TSBAb were measured with recombinant human thyrotropin receptor (rhTSHR)-Chinese hamster ovary cell (rhTSHR-CHO cell) bioassay. RESULTS: At the first survey, the prevalences of positive TSAb, TBII and TSBAb were found in 80.9%, 61.7% and 6.4% of the patients with Graves' disease respectively. TSAb and/or TBII were positive in 91.5% of the patients. The consistent rate of TSAb and TBII was 59.6% in the cases. All indexes mentioned above were higher in the patients than in healthy controls. Positive correlations were found between TSAb and TBII (r = 0.407), TSAb and thyroglobulin (r = 0.301), TSAb and thyroid volume (r = 0.317) respectively. The prevalence of positive TSAb (91.7%) in Graves' patients in iodine excessive area are significantly higher than those in iodine mildly deficient area (66.7%). The positive rates and the titers of TBII, TPOAb and TGAb were not different statistically among the patients in the three communities. At follow-up, the patients with Graves' hyperthyroidism were classified into euthyroid group (G1) and hyperthyroid group (G2) according to their outcomes of the disease. The TSAb titers and the thyroid volume in the cases of G1 decreased significantly, whereas the patients with highly positive TPOAb titers in the first survey and the follow-up were hard to become euthyroid and TSAb may be the secondary factor influencing the thyroid as compared with TPOAb. CONCLUSION: TSAb is more significant than TBII in diagnosing and predicting the outcomes of Graves' hyperthyroidism. The application of both TSAb and TBII could raise the positive rates of thyrotrophin receptor antibody tests. TSAb, TPOAb titers and thyroid volume were factors influencing the prognosis of Graves' hyperthyroidism.
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Autoanticuerpos/sangre , Enfermedad de Graves/diagnóstico , Inmunoglobulinas Estimulantes de la Tiroides/sangre , Yodo/administración & dosificación , Glándula Tiroides/inmunología , Adolescente , Adulto , Anciano , Animales , Células CHO , Cricetinae , Femenino , Estudios de Seguimiento , Enfermedad de Graves/inmunología , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Receptores de Tirotropina/sangreRESUMEN
OBJECTIVE: To investigate the dynamic changes of serum Th1 and Th2 cytokines in patients with postpartum thyroiditis (PPT) during the first postpartum year. METHODS: 21 patients diagnosed as clinical PPT and 11 healthy postpartum women were enrolled in the study. Blood samples were taken before delivery and every 3 months postpartum for testing serum IFNgamma, IL-2, IL-4 and IL-10, which were measured with ELISA method. RESULTS: In patients with PPT, the detection rate of IFNgamma and IL-2 at 6th month postpartum were 19.0% (4/21) and 14.3% (3/21), respectively, being lower than those before delivery [52.4% (11/21) and 61.9% (13/21), respectively, P < 0.05]. The detection rate of IL-4 and IL-10 in patients were 71.4% (15/21) and 95.2% (20/21), respectively. A significant raise when compared with that before delivery (61.9%, 13/21) was seen in IL-10 (P < 0.05). Although Th1 cytokines (IFNgamma, IL-2) declined gradually post-parturition both in healthy postpartum women and PPT patients, yet Th2 cytokines (IL-4, IL-10) showed different tendency in healthy postpartum women and PPT patients. Th2 cytokines declined gradually in healthy postpartum women, while it kept at high level until the 12th month postpartum in the PPT patients. CONCLUSION: In PPT patients, Th2 cytokines show higher levels after delivery. Th2 cells are dominant and protected thyroids from Th1 cells during the course of PPT; this might be helpful to the recovery from disturbance of thyroid autoimmunity.
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Citocinas/sangre , Trastornos Puerperales/inmunología , Células TH1/inmunología , Células Th2/inmunología , Tiroiditis Autoinmune/inmunología , Estudios de Casos y Controles , Ensayo de Inmunoadsorción Enzimática , Femenino , Estudios de Seguimiento , Humanos , Interferón gamma/sangre , Interleucina-10/sangre , Interleucina-2/sangre , Interleucina-4/sangre , Periodo PospartoRESUMEN
OBJECTIVE: To investigate the effects of chronic iodine excess on thyroid function, thyroid peroxidase (TPO) activity, and expression of sodium-iodide symporter (NIS). METHODS: 500 Wistar rats were randomly exposed to 4 doses of iodine 4 microg/d (G0, control), 6 microg/d (G1), 12 microg/d (G2), and 24 microg/d (G3) for 1, 2, 4 and 8 months. The urine iodine and tissue iodine was determined by arsenic/cerium catalyzing spectrophotograph. Radioimmunoassays were used to detect thyrotropin (TSH), free thyroxin (FT4), free triiodothyronine (FT3), total thyroxin (TT4), and total triiodothyronine (TT3). Guaiacol reaction method and potassium iodide oxygenation method were used to determine the activity of TPO. Suspension of single cells from thyroid tissue was made and the positive rate of NIS was determined by flow cytometry. The expression of NIS protein was assayed by immunohistochemistry. RESULTS: The urine iodine levels of G1, G2, and G3 were 1.5, 3, and 6 times of G0 respectively. FT4, FT3, and total iodine were found progressively accumulated in thyroid tissue with the elevation of iodine intake. The TPO activities of G2 and G3 at the 8th month were 0.17 +/- 0.04 and 0.15 +/- 0.03 respectively, both significantly lower than that of G0 (0.4 +/- 0.23, P < 0.05). The levels of iodine intake at different time points of G1-3 were significantly reduced in a iodine-dose dependent manner (r = -0.63 to -0.78, P < 0.01). The 131I intake at month 8 of G1, G2, and G3 were 56%, 49%, and 39% that of G0 respectively. At month 8 the NIS positive rates of G2 and G3 were significantly lower than that of G0 (both P < 0.05). The NIS protein positive rate was positively correlated with NIS protein expression intensity (r = 0.7-0.72, P < 0.01). The iodine content of thyroid tissue was negatively correlated with TPO activity, iodine intake rate, NIS protein positive rate and expression intensity (r = -0.62 to -0.88, P < 0.05). CONCLUSION: Moderate iodine excess continuously suppresses the thyroid iodine uptake and organification, which presents a mechanism for iodine-induced thyroid failure.
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Yoduro Peroxidasa/metabolismo , Yodo/administración & dosificación , Simportadores/metabolismo , Glándula Tiroides/efectos de los fármacos , Animales , Sobredosis de Droga , Femenino , Yodo/farmacocinética , Yodo/toxicidad , Transporte Iónico/efectos de los fármacos , Masculino , Distribución Aleatoria , Ratas , Ratas Wistar , Sodio/metabolismo , Glándula Tiroides/metabolismo , Factores de TiempoRESUMEN
OBJECTIVE: To study the prevalence of thyroid diseases, as well as characteristics of the disease spectrum and thyroid autoimmunity in women at the end of pregnancy. METHODS: Six hundred and sixty-four pregnant women (pregnancy group) and 276 non-pregnant women (control group) were enrolled in the study. Serum thyrotropin (TSH), thyroid peroxidase antibody (TPOAb), free T(3) (FT(3)) and free T(4) (FT(4)) were measured by high-sensitive immunochemiluminescent assay, and urinary iodine was also examined at the end of pregnancy. Overt hyperthyroidism was diagnosed when both TSH < 0.3 mU/L and FT(4) and/or FT(3) levels were elevated. Subclinical hyperthyroidism was diagnosed when TSH < 0.3 mU/L with normal FT(4) and FT(3) levels. The diagnostic criteria for overt hypothyroidism was TSH > 4.8 mU/L accompanied by decreased FT(4), and for subclinical hypothyroidism was TSH > 4.8 mU/L with normal FT(4) and FT(3) levels. RESULTS: (1) The median urinary iodine (MUI) of pregnancy group was 201.5 microg/L, and that of control group was 196.0 microg/L (P > 0.05). Women in the two groups were iodine-adequate. (2) The overall prevalence of thyroid diseases in pregnancy group and control group was 7.8% (52/664) and 6.9% (19/276), respectively (P > 0.05). (3) As for the diseases pattern, there were obvious differences between the two groups. In pregnancy group, the prevalence of hyperthyroidism was lower than that of hypothyroidism (1.1% vs 6.8%, P < 0.01). In control group, the prevalence of hyperthyroidism and hypothyroidism was 4.7% and 2.2%, respectively (P > 0.05). Compared with control group, the prevalence of hyperthyroidism in pregnancy group was much lower (1.1% vs 4.7%, P < 0.01), mainly due to the decrease of overt hyperthyroidism; whereas, the increment of subclinical hypothyroidism resulted in the higher prevalence of hypothyroidism in pregnancy group (6.8% vs 2.2%, P = 0.01). (4) The median TSH level of the healthy women in pregnancy group was significantly higher than that in control group (2.50 vs 1.54 mU/L, P < 0.01). The positive rate of TPOAb in pregnancy women was lower than that in non-pregnancy women (3.3% vs 9.4%, P < 0.01). CONCLUSION: At the end of pregnancy, hypothyroidism accounts for most thyroid diseases. Thyroid autoimmunity is suppressed.
Asunto(s)
Autoanticuerpos/sangre , Glándula Tiroides/inmunología , Glándula Tiroides/fisiopatología , Adulto , Autoinmunidad , China/epidemiología , Femenino , Humanos , Hipotiroidismo/epidemiología , Hipotiroidismo/inmunología , Hipotiroidismo/fisiopatología , Yoduro Peroxidasa/inmunología , Embarazo , Complicaciones del Embarazo/sangre , Complicaciones del Embarazo/inmunología , Complicaciones del Embarazo/fisiopatología , Tercer Trimestre del Embarazo , Prevalencia , Enfermedades de la Tiroides/epidemiología , Enfermedades de la Tiroides/inmunología , Enfermedades de la Tiroides/fisiopatología , Pruebas de Función de la Tiroides , Tirotropina/sangre , Tiroxina/sangre , Triyodotironina/sangreRESUMEN
Multiple endocrine neoplasia 2A (MEN2A) is characterized by the coexistence of tumors that involve two or more endocrine glands within the same patient, and is defined as the occurrence of medullary thyroid carcinoma in association with pheochromocytoma (PHEO) and parathyroid tumors or hyperparathyroidism. The pathogenesis of MEN2A is due to the mutation of a tyrosine kinase receptor that is encoded by the rearrangement during transfection (RET) proto-oncogene. The mutation often occurs in exon 10q11.2. The present study reports the case of a 73-year-old man with severe hypercalcemia, bilateral adrenal PHEO and a thyroid nodule. A genetic panel was obtained, and the RET mutation was indicated. The pedigree of the patient was also studied. Genetic testing of the patient's son indicated heterozygosity for the same mutation at codon 634. The first symptom of the two patients was PHEO, which is uncommon. In addition, varied phenotypes were identified in the two patients. In the present study, the association between the phenotypic variation of the RET gene and the occurrence of MEN2A is discussed.
RESUMEN
The expression of major histocompatibility complex (MHC) class II molecules on thyrocytes has been demonstrated in autoimmune thyroid diseases. However, the role of this aberrant MHC class II in disease development is controversial. In particular, it remains unknown whether MHC class II expression on thyrocytes, which are nonprofessional antigenpresenting cells, plays a role in inducing autoimmune processes. To clarify this issue, we have produced transgenic mice harboring an MHC class II gene ligated to the promoter of the rat TSH receptor. We obtained three lines of transgenic mice, and the expression of MHC class II by the thyrocytes was demonstrated by immunofluorescence staining and flow cytometry. Our examination revealed no obvious abnormalities in thyroid histology or in thyroid autoantibody production in these transgenic mice. Although serum-free T(4) levels were slightly lower than those of their nontransgenic littermates, no transgenic mouse suffered from clinical hypothyroidism or hyperthyroidism. Furthermore, thyroid lymphocytic infiltration was absent, and MHC class II-expressing thyrocytes obtained from transgenic mice failed to stimulate the proliferation of autologous T cells in vitro. Taken together, these results show that transgenic mice with MHC class II molecules on their thyrocytes do not develop apparent autoimmune thyroid diseases, suggesting that aberrant MHC class II expression alone is not sufficient to induce thyroid autoimmunity.
Asunto(s)
Enfermedades Autoinmunes/inmunología , Antígenos de Histocompatibilidad Clase II/biosíntesis , Enfermedades de la Tiroides/inmunología , Glándula Tiroides/inmunología , Animales , Autoanticuerpos/biosíntesis , División Celular , Citometría de Flujo , Técnica del Anticuerpo Fluorescente , Antígenos de Histocompatibilidad Clase II/genética , Activación de Linfocitos , Linfocitos/patología , Ratones , Ratones Endogámicos C3H , Ratones Transgénicos , Regiones Promotoras Genéticas/genética , Receptores de Tirotropina/genética , Linfocitos T/inmunología , Glándula Tiroides/patología , Tiroxina/sangreRESUMEN
OBJECTIVE: To assess the relationship between the biological exposure to iodine and hypothyroidism. METHODS: Logistic regression model was used to analyze the risk factors of hypothyroidism, according to the epidemiologic data of 3761 adults in 3 kinds of rural communities: mild iodine deficiency area (4 natural villages in Panshan County, Liaoning Province), more than adequate iodine (7 natural villages of Zhangwu County, Liaoning Province), and excessive iodine area (2 natural villages of Huanghua City, Hebei Province). RESULTS: More than adequate iodine and excessive iodine were independent risk factors of subclinical hypothyroidism (OR = 3.172 and 6.391, P < 0.05) and overt hypothyroidism (OR = 3.696 and 9.213, P < 0.05). When interactions of iodine exposure and thyroid peroxidase antibody (TPOAb) or thyroglobulin antibody (TgAb) were included, more than adequate iodine was still a risk factor of subclinical hypothyroidism (OR = 2.788, P < 0.01), but had no such effect on overt hypothyroidism. Interaction of more than adequate iodine and positive TgAb significantly affected subclinical hypothyroidism and overt hypothyroidism (OR = 2.656 and 3.347, P < 0.05). CONCLUSION: More than adequate and excessive iodine exposure are independent risk factors of hypothyroidism. The risk of hypothyroidism grows up and thyroid dysfunction becomes more serious with the increasing of the biological exposure to iodine.
Asunto(s)
Hipotiroidismo/epidemiología , Yodo/efectos adversos , Abastecimiento de Agua/análisis , Adulto , Autoantígenos/inmunología , Causalidad , China/epidemiología , Femenino , Humanos , Hipotiroidismo/inducido químicamente , Yoduro Peroxidasa/inmunología , Yodo/deficiencia , Proteínas de Unión a Hierro/inmunología , Modelos Logísticos , Masculino , Prevalencia , Factores de RiesgoRESUMEN
OBJECTIVE: To investigate the relationship between selenium status and thyroid dysfunction in 3 areas with different iodine intake. METHODS: An epidemiological research was performed in the rural communities of Panshan County (iodine-deficient area) and Zhangwu County (iodine-sufficient area), Liaoning Province, and Huanghua County, Hebei Province (iodine-excessive area). Serum selenium, TSH, FT3 and FT4 levels were examined in 329 patients with thyroid dysfunction (including clinical hypothyroidism, subclinical hypothyroidism, clinical hyperthyroidism and subclinical hyperthyroidism) and 183 normal inhabitants. RESULTS: The median serum selenium concentrations in Panshan, Zhangwu and Huanghua were 91.4, 89.1, and 83.2 microg/L respectively. There was no difference in serum selenium levels between the patients with subclinical hypothyroidism, clinical hypothyroidism, and clinical hyperthyroidism and their normal controls. The median serum selenium concentration of the subclinical hyperthyroidism patients was 82.6 microg/L, significantly lower than that of the normal controls (87.3 microg/L). The FT3/FT4 ratio was decreased, the FT4 level was increased in the subclinical hyperthyroidism patients in comparison with the normal controls, and no significant difference in FT3 level was found between them. No significant effect of sex and age was found on serum selenium level of normal inhabitants. In normal controls serum selenium was inversely correlated with serum TSH level, and the subjects with serum selenium < or = 80 microg/L had the median TSH level of 2.10 mU/L, markedly higher than that of the subjects with the serum selenium of 80-100 microg/L (1.29 mU/L) and that of the subjects with the serum selenium of 100 approximately 120 micro g/L (1.28 mU/L). For the thyroid dysfunction patients with positive thyroid auto-antibody (TPOAb) in Zhangwu County, the serum selenium was negatively associated with TPOAb level. The serum selenium level of the TPOAb highly positive group (TPOAb > 600 IU/ml) was 83.6 IU/ml, significantly lower than those of the TPOAb lowly positive group and TPOAb moderately positive group (83.6, 92.9 and 95.6 microg/L respectively). CONCLUSION: No obvious effect of selenium status is found on the development of thyroid dysfunction in these three areas. But selenium deficiency can impair thyroid function by means of disturbing thyroid hormone metabolism and decreasing antioxidant ability of the thyroid.