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1.
Endocr Relat Cancer ; 29(7): 389-401, 2022 05 16.
Artigo em Inglês | MEDLINE | ID: mdl-35521768

RESUMO

Differential diagnosis of thyroid cancer and benign nodules is still one of the most challenging issues in the field of endocrinology. To overcome overdiagnosis of papillary thyroid carcinomas (PTC) and the consecutive overtreatment of multinodular diseases, the search for easily accessible, sensitive and accurate biomarkers is critical. Several micro-RNAs (miRNAs) freely circulating in peripheral blood or enclosed in extracellular vesicles (EVs) have been proposed as potential biomarkers from non-invasive liquid biopsies. However, protocols are rarely comparable and conflicting data exist in the literature. In this work, we aimed to assess the diagnostic value of six micro-RNAs by comparing their expression in thyroid tissue to their abundance in bulk plasma and in plasma-EVs, before and after thyroid surgery. Plasma-EVs were isolated using a sequential density- and size-based fractionation, followed by in-depth characterization, confirming EV purity. Micro-RNA levels were measured by RT-qPCR in thyroid tissue, plasma and plasma-EVs. Among the six candidates, only miR-146b-5p and miR-21a-5p displayed a significant differential abundance in purified plasma-derived EVs from patients with PTC and benign disease. However, no difference could be demonstrated in bulk plasma through our cohort of patients. Overall, our work supports the use of a well-defined protocol of plasma-EV miRNAs purification for biomarker discovery, rather than the use of freely circulating miRNAs in bulk plasma. Our work also demonstrates that standardized pre-analytical and analytical procedures as well as optimized EV-miRNAs detection methods are essential.


Assuntos
Vesículas Extracelulares , MicroRNAs , Neoplasias da Glândula Tireoide , Biomarcadores , Biomarcadores Tumorais/metabolismo , Vesículas Extracelulares/metabolismo , Humanos , MicroRNAs/genética , Câncer Papilífero da Tireoide/metabolismo , Neoplasias da Glândula Tireoide/patologia
2.
Int J Mol Sci ; 22(8)2021 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-33916948

RESUMO

In Hashimoto's thyroiditis (HT), oxidative stress (OS) is driven by Th1 cytokines' response interfering with the normal function of thyrocytes. OS results from an imbalance between an excessive production of reactive oxygen species (ROS) and a lowering of antioxidant production. Moreover, OS has been shown to inhibit Sirtuin 1 (SIRT1), which is able to prevent hypoxia-inducible factor (HIF)-1α stabilization. The aims of this study were to determine the involvement of NADPH-oxidases (NOX), SIRT1, and HIF-1α in HT pathophysiology as well as the status of antioxidant proteins such as peroxiredoxin 1 (PRDX1), catalase, and superoxide dismutase 1 (SOD1). The protein expressions of NOX2, NOX4, antioxidant enzymes, SIRT1, and HIF-1α, as well as glucose transporter-1 (GLUT-1) and vascular endothelial growth factor A (VEGF-A), were analyzed by Western blot in primary cultures of human thyrocytes that were or were not incubated with Th1 cytokines. The same proteins were also analyzed by immunohistochemistry in thyroid samples from control and HT patients. In human thyrocytes incubated with Th1 cytokines, NOX4 expression was increased whereas antioxidants, such as PRDX1, catalase, and SOD1, were reduced. Th1 cytokines also induced a significant decrease of SIRT1 protein expression associated with an upregulation of HIF-1α, GLUT-1, and VEGF-A proteins. With the exception of PRDX1 and SOD1, similar results were obtained in HT thyroids. OS due to an increase of ROS produced by NOX4 and a loss of antioxidant defenses (PRDX1, catalase, SOD1) correlates to a reduction of SIRT1 and an upregulation of HIF 1α, GLUT-1, and VEGF-A. Our study placed SIRT1 as a key regulator of OS and we, therefore, believe it could be considered as a potential therapeutic target in HT.


Assuntos
Doença de Hashimoto/etiologia , Doença de Hashimoto/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Estresse Oxidativo , Sirtuína 1/genética , Células Th1/imunologia , Células Th1/metabolismo , Fator A de Crescimento do Endotélio Vascular/genética , Adulto , Doenças Autoimunes/etiologia , Doenças Autoimunes/metabolismo , Autoimunidade/genética , Biomarcadores , Citocinas/genética , Citocinas/metabolismo , Feminino , Imunofluorescência , Regulação da Expressão Gênica , Doença de Hashimoto/diagnóstico , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , NADPH Oxidase 2/genética , NADPH Oxidase 2/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Sirtuína 1/metabolismo , Superóxido Dismutase-1/metabolismo , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Timócitos/imunologia , Timócitos/metabolismo , Testes de Função Tireóidea , Glândula Tireoide/imunologia , Glândula Tireoide/metabolismo , Glândula Tireoide/patologia , Fator A de Crescimento do Endotélio Vascular/metabolismo , Adulto Jovem
3.
Int J Mol Sci ; 23(1)2021 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-35008579

RESUMO

Graves' disease (GD) is an autoimmune thyroiditis often associated with Graves' orbitopathy (GO). GD thyroid and GO orbital fat share high oxidative stress (OS) and hypervascularization. We investigated the metabolic pathways leading to OS and angiogenesis, aiming to further decipher the link between local and systemic GD manifestations. Plasma and thyroid samples were obtained from patients operated on for multinodular goiters (controls) or GD. Orbital fats were from GO or control patients. The NADPH-oxidase-4 (NOX4)/HIF-1α/VEGF-A signaling pathway was investigated by Western blotting and immunostaining. miR-199a family expression was evaluated following quantitative real-time PCR and/or in situ hybridization. In GD thyroids and GO orbital fats, NOX4 was upregulated and correlated with HIF-1α stabilization and VEGF-A overexpression. The biotin assay identified NOX4, HIF-1α and VEGF-A as direct targets of miR-199a-5p in cultured thyrocytes. Interestingly, GD thyroids, GD plasmas and GO orbital fats showed a downregulation of miR-199a-3p/-5p. Our results also highlighted an activation of STAT-3 signaling in GD thyroids and GO orbital fats, a transcription factor known to negatively regulate miR-199a expression. We identified NOX4/HIF-1α/VEGF-A as critical actors in GD and GO. STAT-3-dependent regulation of miR-199a is proposed as a common driver leading to these events in GD thyroids and GO orbital fats.


Assuntos
Tecido Adiposo/metabolismo , Regulação para Baixo/genética , Doença de Graves/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , MicroRNAs/genética , NADPH Oxidase 4/genética , Glândula Tireoide/metabolismo , Fator A de Crescimento do Endotélio Vascular/genética , Adulto , Feminino , Oftalmopatia de Graves/genética , Oftalmopatia de Graves/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Transdução de Sinais/genética
4.
Thyroid ; 31(4): 627-637, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-32977740

RESUMO

Background: Even though the clinical features of Graves' orbitopathy (GO) are well known, its exact pathogenesis remains controversial. The imbalance of redox homeostasis in the connective tissue could play a crucial role leading to an inflammatory state and edema of soft orbital tissues, thus contributing to orbital hypoxia and increase in hypoxia-inducible factor (HIF)-1α. This oxidative stress appears to target the orbital cells such as fibroblasts and also adipocytes. This study aims to explore which pathways can lead to the aforementioned oxidative stress in GO adipose cells and therefore offers new plausible therapeutic targets. Methods: Orbital fat samples were obtained from patients with GO (Western blot [WB]: n = 8, immunohistochemistry [IHC]: n = 8) and from control patients (WB: n = 5, IHC: n = 3-5). They were processed for WB analysis and IHC of the antioxidants (catalase, superoxide dismutase 1) and for HIF-1α. The expression of caveolin-1 (Cav-1) and deiodinase 3 (DIO3), known to be regulated by HIF-1α, was also analyzed by WB and IHC, as well as the targets of Cav-1: glucose transporter type 4 (Glut-4), NADPH oxidase (NOX)-2, and endothelial nitric oxide synthase (eNOS). Triiodothyronine (T3) expression was also analyzed by IHC. Results: In GO adipocytes, the expression of catalase was reduced, whereas that of HIF-1α was strongly increased. A decreased local T3 supply was associated with DIO3 upregulation. The low expression of Cav-1 in GO adipocytes was associated not only with low expression of Glut-4 but also with an increased expression of NOX-2 and active eNOS phosphorylated on serine 1177. Conclusions: Cav-1 and DIO3, both sensitive to hypoxia and to the increase of HIF-1α, play a pivotal role in the oxidative stress in GO adipocytes. DIO3 regulates the cellular supply of T3, which is essential for the cell homeostasis. Cav-1 determines the cellular glucose supply through Glut-4 and regulates the activity of NOX-2 generating superoxide anions and that of eNOS generating nitric oxide (NO).


Assuntos
Adipócitos/enzimologia , Caveolina 1/metabolismo , Oftalmopatia de Graves/enzimologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Iodeto Peroxidase/metabolismo , Estresse Oxidativo , Adipócitos/patologia , Adulto , Estudos de Casos e Controles , Caveolina 1/genética , Células Cultivadas , Feminino , Regulação da Expressão Gênica , Transportador de Glucose Tipo 4/metabolismo , Oftalmopatia de Graves/genética , Oftalmopatia de Graves/patologia , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Iodeto Peroxidase/genética , Masculino , Pessoa de Meia-Idade , NADPH Oxidase 2/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Superóxidos/metabolismo , Tri-Iodotironina/metabolismo
5.
Transplantation ; 104(4): 731-743, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31764761

RESUMO

BACKGROUND: The optimal perfusate partial pressure of oxygen (PO2) during hypothermic machine perfusion (HMP) is unknown. The aims of the study were to determine the functional, metabolic, structural, and flow dynamic effects of low and high perfusate PO2 during continuous HMP in a pig kidney ischemia-reperfusion autotransplant model. METHODS: The left kidneys of a ±40 kg pigs were exposed to 30 minutes of warm ischemia and randomized to receive 22-hour HMP with either low perfusate PO2 (30% oxygen, low oxygenated HMP [HMPO2]) (n = 8) or high perfusate PO2 (90% oxygen, HMPO2high) (n = 8), before autotransplantation. Kidneys stored in 22-hour standard HMP (n = 6) and 22-hour static cold storage (n = 6) conditions served as controls. The follow-up after autotransplantation was 13 days. RESULTS: High PO2 resulted in a 3- and 10-fold increase in perfusate PO2 compared with low HMPO2 and standard HMP, respectively. Both HMPO2 groups were associated with superior graft recovery compared with the control groups. Oxygenation was associated with a more rapid and sustained decrease in renal resistance. While there was no difference in functional outcomes between both HMPO2 groups, there were clear metabolic differences with an inverse correlation between oxygen provision and the concentration of major central metabolites in the perfusion fluid but no differences were observed by oxidative stress and metabolic evaluation on preimplantation biopsies. CONCLUSIONS: While this animal study does not demonstrate any advantages for early graft function for high perfusate PO2, compared with low perfusate PO2, perfusate metabolic profile analysis suggests that aerobic mechanism is better supported under high perfusate PO2 conditions.


Assuntos
Hipotermia Induzida/instrumentação , Transplante de Rim/instrumentação , Rim/cirurgia , Oxigênio/metabolismo , Perfusão/instrumentação , Animais , Biomarcadores/sangue , Isquemia Fria , Creatinina/sangue , Metabolismo Energético , Desenho de Equipamento , Feminino , Hipotermia Induzida/efeitos adversos , Rim/metabolismo , Rim/patologia , Transplante de Rim/efeitos adversos , Modelos Animais , Pressão Parcial , Perfusão/efeitos adversos , Distribuição Aleatória , Sus scrofa , Fatores de Tempo , Transplante Autólogo , Isquemia Quente
6.
Thyroid ; 26(10): 1499-1512, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27599561

RESUMO

BACKGROUND: The dual oxidases (Duox) are involved in hydrogen peroxide generation, which is essential for thyroid hormone synthesis, and therefore they are markers of thyroid function. During inflammation, cytokines upregulate DUOX gene expression in the airway and the intestine, suggesting a role for these proteins in innate immunity. It was previously demonstrated that interleukin-4 (IL-4) upregulates DUOX gene expression in thyrocytes. Although the role of IL-4 in autoimmune thyroid diseases has been studied extensively, the effects of IL-4 on thyroid physiology remain largely unknown. Therefore, a new animal model was generated to study the impact of IL-4 on thyroid function. METHODS: Transgenic (Thyr-IL-4) mice with thyroid-targeted expression of murine IL-4 were generated. Transgene expression was verified at the mRNA and protein level in thyroid tissues and primary cultures. The phenotype of the Thyr-IL-4 animals was characterized by measuring serum thyroxine (T4) and thyrotropin levels and performing thyroid morphometric analysis, immunohistochemistry, whole transcriptome sequencing, quantitative reverse transcription polymerase chain reaction, and ex vivo thyroid function assays. RESULTS: Thyrocytes from two Thyr-IL-4 mouse lines (#30 and #52) expressed IL-4, which was secreted into the extracellular space. Although 10-month-old transgenic animals had T4 and thyrotropin serum levels in the normal range, they had altered thyroid follicular structure with enlarged follicles composed of elongated thyrocytes containing numerous endocytic vesicles. These follicles were positive for T4 staining the colloid, indicating their capacity to produce thyroid hormones. RNA profiling of Thyr-IL-4 thyroid samples revealed modulation of multiple genes involved in inflammation, while no major leukocyte infiltration could be detected. Upregulated expression of Duox1, Duoxa1, and the pendrin anion exchanger gene (Slc26a4) was detected. In contrast, the iodide symporter gene Slc5a5 was markedly downregulated resulting in impaired iodide uptake and reduced thyroid hormone levels in transgenic thyroid tissue. Hydrogen peroxide production was increased in Thyr-IL-4 thyroid tissue compared with wild-type animals, but no significant oxidative stress could be detected. CONCLUSIONS: This is the first study to show that ectopic expression of IL-4 in thyroid tissue upregulates Duox1/Duoxa1 and Slc26a4 expression in the thyroid. The present data demonstrate that IL-4 could affect thyroid morphology and function, mainly by downregulating Slc5a5 expression, while maintaining a normal euthyroid phenotype.


Assuntos
Proteínas de Transporte de Ânions/metabolismo , Oxidases Duais/metabolismo , Interleucina-4/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Proteínas Nucleares/metabolismo , Glândula Tireoide/metabolismo , Regulação para Cima , Absorção Fisiológica , Animais , Proteínas de Transporte de Ânions/genética , Células Cultivadas , Regulação para Baixo , Oxidases Duais/genética , Perfilação da Expressão Gênica , Peróxido de Hidrogênio/metabolismo , Interleucina-4/genética , Iodetos/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Proteínas do Tecido Nervoso/genética , Proteínas Nucleares/genética , Transportadores de Sulfato , Simportadores/genética , Simportadores/metabolismo , Glândula Tireoide/citologia , Glândula Tireoide/imunologia , Tireotropina/sangue , Tireotropina/metabolismo , Tiroxina/sangue , Tiroxina/metabolismo
7.
Thyroid ; 26(9): 1320-31, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27324467

RESUMO

BACKGROUND: Peroxisome proliferator-activated receptor γ (PPARγ) is a transcription factor that regulates the expression of multiple target genes involved in several metabolic pathways as well as in inflammation. The expression and cell localization of caveolin-1 (Cav-1), thyroperoxidase (TPO), and dual oxidase (DUOX), involved in extracellular iodination, is modulated by Th1 cytokines in human normal thyroid cells and in Hashimoto's thyroiditis (HT). OBJECTIVES: The objectives of this study were (i) to analyze the PPARγ protein and mRNA expression at the follicular level in HT versus controls in correlation with the one of Cav-1; (ii) to study the effects of Th1 cytokines on PPARγ and catalase expression in human thyrocyte primary cultures; and (iii) to study the effects of pioglitazone, a PPARγ agonist, on thyroxisome components (Cav-1, TPO, DUOX) and on catalase, involved in antioxidant defense. RESULTS: Although the global expression of PPARγ in the whole gland of patients with HT was not modified compared with controls, there was great heterogeneity among glands and among follicles within the same thyroid. Besides normal (type 1) follicles, there were around inflammatory zones, hyperactive (type 2) follicles with high PPARγ and Cav-1 expression, and inactive (type 3) follicles which were unable to form thyroxine and did not express PPARγ or Cav-1. In human thyrocytes in primary culture, Th1 cytokines decreased PPARγ and catalase expression; pioglitazone increased Cav-1, TPO, and catalase expression. CONCLUSION: PPARγ may play a central role in normal thyroid physiology by upregulating Cav-1, essential for the organization of the thyroxisome and extracellular iodination. By upregulating catalase, PPARγ may also contribute to cell homeostasis. The inhibitory effect of Th1 cytokines on PPARγ expression may be considered as a new pathogenetic mechanism for HT, and the use of PPARγ agonists could open a new therapeutic approach.


Assuntos
Catalase/metabolismo , Caveolina 1/metabolismo , Hipoglicemiantes/farmacologia , PPAR gama/agonistas , Tiazolidinedionas/farmacologia , Células Epiteliais da Tireoide/efeitos dos fármacos , Regulação para Cima/efeitos dos fármacos , Autoantígenos/metabolismo , Células Cultivadas , Oxidases Duais/metabolismo , Doença de Hashimoto/metabolismo , Humanos , Iodeto Peroxidase/metabolismo , Proteínas de Ligação ao Ferro/metabolismo , Pioglitazona , Células Epiteliais da Tireoide/metabolismo , Glândula Tireoide/efeitos dos fármacos , Glândula Tireoide/metabolismo
8.
Histol Histopathol ; 31(8): 897-909, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26838679

RESUMO

Despite efforts to optimize iodine supply in iodine deficient countries, iodine deficiency (ID) remains a global problem worldwide. Activation of the local microvasculature by ID in the thyroid gland aims at improving the local supply of iodide. For this purpose, the thyrocytes secrete vascular endothelial growth factor (VEGF) that acts on adjacent capillaries, via a reactive oxygen species (ROS)/Hypoxia Inducible factor (HIF)-dependent pathway. Beside the thyroid, other organs including salivary glands and the stomach do express the sodium/iodide symporter (NIS) and are able to take iodide up, potentially rendering them sensitive to ID. To verify this hypothesis, ID-induced effects on the local microvasculature were studied in salivary glands and in the stomach. ID was induced by feeding young mice with an iodide-deficient diet and NIS inhibitor perchlorate in the drinking water. In salivary glands, ID induced a transient increase in HIF-1α protein expression accompanied by a transient, VEGF-dependent increase in blood flow. In the gastric mucosa, ID transiently increased VEGF expression in the mucin-secreting epithelium and in ghrelin-secreting endocrine cells. These observations suggest that microvascular changes in response to ID occur in NIS-expressing tissues other than the thyroid. NIS expressing cells could be viewed as iodide sensors that respond to ID by inducing vascular changes, probably to optimize iodide bioavailability at regional or systemic levels.


Assuntos
Mucosa Gástrica/metabolismo , Iodo/metabolismo , Microvasos , Glândulas Salivares/metabolismo , Simportadores/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Animais , Western Blotting , Modelos Animais de Doenças , Imunofluorescência , Iodo/deficiência , Camundongos , Glândulas Salivares/irrigação sanguínea , Sódio/metabolismo , Estômago/irrigação sanguínea
9.
Thyroid ; 25(9): 1033-42, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26176182

RESUMO

BACKGROUND: Graves' orbitopathy (GO) is the main extrathyroidal manifestation associated with Graves' disease (GD). It is characterized by reduced eye motility due to an increased volume of orbital fat and/or of extraocular muscles (EOMs) infiltrated by fibrosis and adipose tissue. The pathogenetic mechanisms leading to fibrosis and adipogenesis are mainly based on the interaction between orbital fibroblasts and immune cells (lymphocytes and mast cells) infiltrating the GO EOMs. METHODS: Analysis of the morphological status, oxidative stress (OS), and antioxidant defenses in the orbital muscular cells and adipocytes in GO patients compared with controls was conducted. RESULTS: Both cell types are affected by OS, as shown by the increased expression of 4-hydroxynonenal, which leads to apoptosis in muscular cells. However, the EOMs and the adipocytes possess antioxidant defenses (peroxiredoxin 5 and catalase) against the OS, which are also upregulated in thyrocytes in GD. The expression of adiponectin (ApN) and proliferator-activated receptor gamma (PPARγ) is also increased in GO muscular cells and adipocytes. OS and antioxidant proteins expression are correlated to the level of blood antithyrotropin receptor antibodies (TSHR-Ab). CONCLUSION: Even when TSHR-Ab level is normalized, OS and antioxidant protein expression is high in EOM muscular cells and adipocytes in GO compared with controls. This justifies a supplementation with antioxidants in active as well as chronic GO patients. Orbital muscular cells are also the sources of PPARγ and ApN, which have direct or indirect local protective effects against OS. Modulation of these proteins could be considered as a future therapeutic approach for GO.


Assuntos
Adipócitos/metabolismo , Adiponectina/metabolismo , Doença de Graves/metabolismo , Oftalmopatia de Graves/metabolismo , Músculo Esquelético/metabolismo , Órbita/patologia , Estresse Oxidativo , Adipócitos/citologia , Adolescente , Adulto , Idoso , Antioxidantes/metabolismo , Apoptose , Biópsia , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Músculos Oculomotores/citologia , PPAR gama/metabolismo , Receptores da Tireotropina/metabolismo , Glândula Tireoide/citologia , Regulação para Cima
10.
Future Oncol ; 11(19): 2681-2695, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26039564

RESUMO

ABSTRACT In the past decade, the approach to patients with metastatic non-small-cell lung cancer has relied on chemotherapy and on targeted agents for molecularly selected subgroups of patients. Recent work has introduced immunotherapy as another area of progress, and likely as a new treatment paradigm in the near future. While the large Phase III studies with cancer vaccination with the current technologies remain at present disappointing, the immunomodulation strategies with immune checkpoint inhibitors have delivered remarkable results in expanded Phase I studies and are now intensively studied in large Phase III studies. This review summarizes the past decade of immunotherapy for non-small-cell lung cancer, gives an updated overview of trials in this field, and the context of future development in this exciting field.

11.
J Clin Endocrinol Metab ; 99(5): 1722-32, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24476075

RESUMO

CONTEXT: Hashimoto's thyroiditis (HT) and Graves' disease (GD) are thyroid autoimmune disorders driven by Th1 and Th2 immune responses, respectively. Caveolin-1 (Cav-1), thyroid peroxidase (TPO), and dual oxidase (DUOX) are thought to be part of the thyroxisome, which is essential to maintain thyroid hormone synthesis, at the apical membrane. OBJECTIVES: To analyze the thyroxisome in HT and GD thyroids, we investigated Cav-1, DUOX, and TPO expression as well as markers of oxidative stress (OS), cell proliferation, apoptosis, and antioxidant defenses. The effects of cytokines on Cav-1 expression were analyzed in vitro. RESULTS: In HT, the decrease in Cav-1, DUOX, and TPO expression was marked in follicles having the morphological aspect of active follicles in normal glands and thus called active-like follicles. T4 was not detected in the colloid but in the cytoplasm as well as DUOX and TPO. These abnormalities were associated with increased OS and cell damage. In the hypofunctioning follicles of HT and normal thyroids, Cav-1, DUOX, and TPO were not expressed. In GD, they were expressed at the apical pole of thyrocytes, and T4 accumulated in the colloid of all follicles. Th1 cytokines IL-1α/interferonγ decreased Cav-1 expression in vitro, whereas the Th2 cytokine IL-4 had no effect. CONCLUSION: Th1 cytokine-induced down-regulation of Cav-1 could be responsible for intracytoplasmic T4 synthesis and mislocalization of DUOX and TPO, suggesting an important role for Cav-1 in the preservation of thyroxisome integrity. The thyroxisome's disruption, leading to uncontrolled OS and cell apoptosis, is a key, event in HT pathogenesis.


Assuntos
Caveolina 1/metabolismo , Doença de Graves/metabolismo , Doença de Hashimoto/metabolismo , Iodeto Peroxidase/metabolismo , NADPH Oxidases/metabolismo , Glândula Tireoide/metabolismo , Adulto , Apoptose/fisiologia , Autoanticorpos , Proliferação de Células , Oxidases Duais , Doença de Graves/imunologia , Doença de Graves/patologia , Doença de Hashimoto/imunologia , Doença de Hashimoto/patologia , Humanos , Estresse Oxidativo/fisiologia , Glândula Tireoide/imunologia , Glândula Tireoide/patologia
12.
J Rehabil Res Dev ; 48(1): 43-58, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21328162

RESUMO

Chronic whiplash is a debilitating condition characterized by increased sensitivity to painful stimuli, maladaptive illness beliefs, inappropriate attitudes, and movement dysfunctions. Previous work in people with chronic low back pain and chronic fatigue syndrome indicates that pain neurophysiology education is able to improve illness beliefs and attitudes as well as movement performance. This single-case study (A-B-C design) with six patients with chronic whiplash associated disorders (WAD) was aimed at examining whether education about the neurophysiology of pain is accompanied by changes in symptoms, daily functioning, pain beliefs, and behavior. Periods A and C represented assessment periods, while period B consisted of the intervention (pain neurophysiology education). Results showed a significant decrease in kinesiophobia (Tampa Scale for Kinesiophobia), the passive coping strategy of resting (Pain Coping Inventory), self-rated disability (Neck Disability Index), and photophobia (WAD Symptom List). At the same time, significantly increased pain pressure thresholds and improved pain-free movement performance (visual analog scale on Neck Extension Test and Brachial Plexus Provocation Test) were established. Although the current results need to be verified in a randomized, controlled trial, they suggest that education about the physiology of pain is able to increase pain thresholds and improve pain behavior and pain-free movement performance in patients with chronic WAD.


Assuntos
Cognição , Dor/psicologia , Educação de Pacientes como Assunto/métodos , Traumatismos em Chicotada/reabilitação , Adaptação Psicológica , Adolescente , Adulto , Idoso , Doença Crônica , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Movimento , Dor/etiologia , Dor/reabilitação , Medição da Dor , Limiar da Dor , Projetos Piloto , Desempenho Psicomotor , Índice de Gravidade de Doença , Inquéritos e Questionários , Traumatismos em Chicotada/complicações , Adulto Jovem
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