Shexiang Baoxin Pill Regulates Intimal Hyperplasia, Migration, and Apoptosis after Platelet-Derived Growth Factor-BB-Stimulation of Vascular Smooth Muscle Cells via miR-451 / 中国结合医学杂志

OBJECTIVE@#To investigate the regulatory roles of Shexiang Baoxin Pill (SXBXW) in neointimal formation and vascular smooth muscle cells (VSMCs) invasion and apoptosis as well as the potential molecular mechanisms using cultured VSMCs model of vascular injury (platelet-derived growth factor (PDGF)-BB-stimulated) in vitro.@*METHODS@#VSMCs were randomly assigned to 5 groups: blank, PDGF-BB (20 ng/mL+ 0.1% DMSO), SXBXW-L (PDGF-BB 20 ng/mL + SXBXW low dose 0.625 g/L), SXBXW-M (PDGF-BB 20 ng/mL + SXBXW medium dose 1.25 g/L) and SXBXW-H (PDGF-BB 20 ng/mL+ SXBXW high dose 2.5 g/L) group. Cell proliferation was assessed using cell counting kit-8 (CCK-8) assay and bromodeoxyuridine (BrdU) incorporation assay, the migration effects were detected by Transwell assay, cell apoptosis rate was measured by the Annexin V/propidium iodide (PI) apoptosis kit. The markers of contractile phenotype of VSMCs were detected with immunofluorescent staining. To validate the effects of miR-451 in regulating proliferation, migration and apoptosis treated with SXBXW, miR-451 overexpression experiments were performed, the VSMCs were exposed to PDGF-BB 20 ng/mL + 0.1% DMSO and later divided into 4 groups: mimic-NC (multiplicity of infection, MOI=50), SXBXW (1.25 g/L) + mimic-NC, mimic-miR451 (MOI=50), and SXBXW (1.25 g/L) + mimic-miR451, and alterations of proteins related to the miR-451 pathway were analyzed using Western blot.@*RESULTS@#PDGF-BB induced VSMCs injury causes acceleration of proliferation and migration. SXBXW inhibited phenotypic switching, proliferation and migration and promoted cell apoptosis in PDGF-BB-induced VSMCs. In addition, miR-451 was shown to be down-regulated in the VSMCs following PDGF-BB stimulation. SXBXW treatment enhanced the expression of miR-451 in PDGF-BB-induced VSMCs (P<0.05). Compared with SXBXW + mimic-NC and mimic-miR451 groups, the expression of tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta (Ywhaz) and p53 was further reduced in SXBXW + mimic-miR451 group, while activating transcription factor 2 (ATF2) was increased in VSMCs (P<0.05).@*CONCLUSION@#SXBXW regulated proliferation, migration and apoptosis via activation of miR-451 through ATF2, p53 and Ywhaz in PDGF-BB-stimulated VSMCs.

Osteopontin expression in reactive lesions of gingiva

Reactive proliferations of the gingiva comprise lesions such as pyogenic granuloma (PG), inflammatory fibroepithelial hyperplasia (IFH), peripheral ossifying fibroma (POF), and peripheral giant cell lesion. Osteopontin (OPN) has a dual role, it promotes mineralization when it is bound to solid substrate, and on the other hand, it inhibits mineralization when it is seen in association with solution. Objectives The study aimed to evaluate the expression of osteopontin in normal gingival tissue and different types of focal reactive proliferations of gingival tissue, and its role in the development of calcification within it. Material and Methods The presence and distribution of osteopontin was assessed using immunohistochemistry in five cases of normal gingival tissue and 30 cases of focal reactive proliferations of gingiva. Results There was no expression of osteopontin in normal subjects. Few cases of pyogenic granuloma, inflammatory fibroepithelial hyperplasia, and all the cases of peripheral ossifying fibroma showed positivity for osteopontin in the inflammatory cells, stromal cells, extracellular matrix, and in the calcifications. Conclusion The expression of osteopontin in all the cases of peripheral ossifying fibroma speculates that the majority of the cases of peripheral ossifying fibroma originate from the periodontal ligament cells. The treatment modalities for peripheral ossifying fibroma should differ from other focal reactive proliferations of gingiva. .

Differential expression of stem cell-like proteins in normal, hyperplastic and dysplastic oral epithelium

Objective The identification of stem cells (SC) remains challenging. In the human oral mucosal epithelium, these cells are believed to be in the basal layer (stem cell niche), but their exact location is unclear. The aim of this study was to examine the dysplastic oral epithelium for these SC-like proteins in order to assess their diagnostic value as biomarkers complementing the histological grading of dysplasia. Material and Methods Thirty oral epithelial dysplasia (OED), 25 oral lichen planus (OLP), 10 oral hyperkeratosis and 5 normal oral epithelium (OE) were immunohistochemically examined for four SC markers [integrin β1, neuron-glial-2 (NG2), notch 1 (N1) and keratin 15 (K15)]. Results Three of four SC markers were heterogeneously detected in all samples. K15 overexpression in the lower two-thirds of severe OED suggests an expanded SC niche. Integrin β1 distribution pattern was not measurably different between OEDs and control. NG2 was almost negative to absent in all samples examined. N1 expression was weak and highly variable in normal and dysplastic epithelium, making it an unreliable epithelial stem cell marker. Conclusions Present findings suggest that these markers were unable to identify individual epithelial stem cells. Instead, subpopulations of cells, most probably stem cells and transit amplifying cells with stem cell-like properties were identified in the dysplastic oral epithelium. The characteristic expressions of K15 might be of diagnostic value for oral dysplasia and should be investigated further. .

Expression of claudin, paxillin and FRA-1 in non-nodular breast lesions in association with microcalcifications / Expressão de claudina, paxilina e FRA-1 em lesões mamárias não nodulares associadas a microcalcificações

CONTEXT AND OBJECTIVE The possible role of adhesion molecules in early breast carcinogenesis has been shown in the literature. We aimed to analyze early adhesion imbalances in non-nodular breast lesions and their association with precursor lesions, in order to ascertain whether these alterations exist and contribute towards early carcinogenesis. DESIGN AND SETTING Retrospective cross-sectional study based on medical records at a private radiological clinic in São Paulo, Brazil. METHODS We retrospectively reviewed the medical records of all consecutive women attended between August 2006 and July 2007 who presented mammographic evidence of breast microcalcifications classified as Breast Imaging Reporting and Data System Atlas (BI-RADS) type 4. These women underwent stereotaxic biopsy. Clinical, radiological and pathological data were collected, and immunohistochemical assays searched for claudin, paxillin, FRA-1 and HER-2. RESULTS Over this period, 127 patients were evaluated. Previous BI-RADS diagnoses showed that 69 cases were in category 4A, 47 in 4B and 11 in 4C. Morphological assessment showed benign entities in 86.5%. Most of the benign lesions showed preserved claudin expression, associated with paxillin (P < 0.001). Paxillin and HER-2 expressions were correlated. FRA-1 expression was also strongly associated with HER-2 expression (P < 0.001). CONCLUSIONS Although already present in smaller amounts, imbalance of adhesion molecules is not necessarily prevalent in non-nodular breast lesions. Since FRA-1 expression reached statistically significant correlations with radiological and morphological diagnoses and HER-2 status, it may have a predictive role in this setting. .

CONTEXTO E OBJETIVO A literatura tem mostrado a importância de moléculas de adesão na carcinogênese precoce de mama. Objetivamos analisar desequilíbrios precoces de adesão em lesões não nodulares da mama e associação com lesões precursoras, a fim de verificar se essas alterações existem e contribuem com a carcinogênese. TIPO DE ESTUDO E LOCAL Estudo retrospectivo baseado em prontuários médicos, numa clínica radiológica privada em São Paulo, Brasil. MÉTODOS Revisamos retrospectivamente prontuários de todas as mulheres consecutivamente atendidas com evidência mamográfica de microcalcificações mamárias, classificadas como tipo 4 do Breast Imaging Reporting and Data System Atlas (BI-RADS) entre agosto de 2006 e julho de 2007. Elas foram submetidas a biópsia estereotáxica. Dados clínicos, radiológicos e histopatológicos foram coletados e ensaios de imunoistoquímica procuraram por claudina, paxilina, HER-2 e FRA-1. RESULTADOS No período, 127 pacientes foram avaliadas. Diagnósticos de BI-RADS anteriores tinham 69 casos na categoria 4A, 47 em 4B, e 11 em 4C. A avaliação morfológica mostrou entidades benignas em 86,5%. A maioria das lesões benignas mostrou expressão preservada de claudina, associada a paxilina (P < 0,001). Expressões de paxilina e HER-2 foram correlacionadas. Expressão de FRA-1 associou-se à de HER-2 (P < 0,001). CONCLUSÕES Embora já presente em menor quantidade, o desequilíbrio de moléculas de adesão não é necessariamente prevalente em lesões mamárias nodulares e talvez a expressão de FRA-1 possa ter um papel preditivo neste cenário, uma vez que atingiu correlações ...

PPARgamma modulates vascular smooth muscle cell phenotype via a protein kinase G-dependent pathway and reduces neointimal hyperplasia after vascular injury

Vascular smooth muscle cells (VSMCs) undergo phenotypic changes in response to vascular injury such as angioplasty. Protein kinase G (PKG) has an important role in the process of VSMC phenotype switching. In this study, we examined whether rosiglitazone, a peroxisome proliferator-activated receptor (PPAR)-gamma agonist, could modulate VSMC phenotype through the PKG pathway to reduce neointimal hyperplasia after angioplasty. In vitro experiments showed that rosiglitazone inhibited the phenotype change of VSMCs from a contractile to a synthetic form. The platelet-derived growth factor (PDGF)-induced reduction of PKG level was reversed by rosiglitazone treatment, resulting in increased PKG activity. This increased activity of PKG resulted in phosphorylation of vasodilator-stimulated phosphoprotein at serine 239, leading to inhibited proliferation of VSMCs. Interestingly, rosiglitazone did not change the level of nitric oxide (NO) or cyclic guanosine monophosphate (cGMP), which are upstream of PKG, suggesting that rosiglitazone influences PKG itself. Chromatin immunoprecipitation assays for the PKG promoter showed that the activation of PKG by rosiglitazone was mediated by the increased binding of Sp1 on the promoter region of PKG. In vivo experiments showed that rosiglitazone significantly inhibited neointimal formation after balloon injury. Immunohistochemistry staining for calponin and thrombospondin showed that this effect of rosiglitazone was mediated by modulating VSMC phenotype. Our findings demonstrate that rosiglitazone is a potent modulator of VSMC phenotype, which is regulated by PKG. This activation of PKG by rosiglitazone results in reduced neointimal hyperplasia after angioplasty. These results provide important mechanistic insight into the cardiovascular-protective effect of PPARgamma.

Glucose-dependent insulinotropic peptide receptor overexpression in adrenocortical hyperplasia in MEN1 syndrome without loss of heterozygosity at the 11q13 locus

BACKGROUND: The molecular mechanisms involved in the genesis of the adrenocortical lesions seen in MEN1 syndrome (ACL-MEN1) remain poorly understood; loss of heterozygosity at 11q13 and somatic mutations of MEN1 are not usually found in these lesions. Thus, additional genes must be involved in MEN1 adrenocortical disorders. Overexpression of the glucose-dependent insulinotropic peptide receptor has been shown to promote adrenocortical tumorigenesis in a mice model and has also been associated with ACTH-independent Cushing syndrome in humans. However, to our knowledge, the status of glucose-dependent insulinotropic peptide receptor expression in adrenocortical lesions in MEN1 has not been previously investigated. OBJECTIVE: To evaluate glucose-dependent insulinotropic peptide receptor expression in adrenocortical hyperplasia associated with MEN1 syndrome. MATERIALS/METHODS: Three adrenocortical tissue samples were obtained from patients with previously known MEN1 germline mutations and in whom the presence of a second molecular event (a new MEN1 somatic mutation or an 11q13 loss of heterozygosity) had been excluded. The expression of the glucose-dependent insulinotropic peptide receptor was quantified by qPCR using the DDCT method, and b-actin was used as an endogenous control. RESULTS: The median of glucose-dependent insulinotropic peptide receptor expression in the adrenocortical lesions associated with MEN1 syndrome was 2.6-fold (range 1.2 to 4.8) higher than the normal adrenal controls (p = 0.02). CONCLUSION: The current study represents the first investigation of glucose-dependent insulinotropic peptide receptor expression in adrenocortical lesions without 11q13 loss of heterozygosity in MEN1 syndrome patients. Although we studied a limited number of cases of MEN1 adrenocortical lesions retrospectively, our preliminary data suggest an involvement of glucose-dependent insulinotropic peptide receptor overexpression in the etiology of adrenocortical hyperplasia. New prospective studies will be able to clarify the exact role of the glucose-dependent insulinotropic peptide receptor in the molecular pathogenesis of MEN1 adrenocortical lesions.

Analysis of glucose-dependent insulinotropic peptide receptor (GIPR) and luteinizing hormone receptor (LHCGR) expression in human adrenocortical hyperplasia / Análise da expressão dos receptores do peptídeo insulinotrópico dependente de glicose (GIPR) e do hormônio luteinizante (LHCGR) nas hiperplasias adrenocorticais humanas

OBJECTIVE: To analyze the aberrant expression of the GIPR and LHCGR in different forms of adrenocortical hyperplasia: ACTH-independent macronodular adrenal hyperplasia (AIMAH), primary pigmented nodular adrenocortical disease (PPNAD) and diffuse adrenal hyperplasia secondary to Cushing's disease (DAHCD). METHODS: We quantified GIPR and LHCGR expressions using real time PCR in 20 patients with adrenocortical hyperplasia (seven with AIMAH, five with PPNAD, and eight with DAHCD). Normal adrenals tissues were used as control and the relative expression was compared with β-actin. RESULTS: GIPR and LHCGR expressions were demonstrated in all tissues studied. Median GIPR and LHCGR mRNA levels were 1.6; 0.4; 0.5 and 1.3; 0.9; 1.0 in adrenocortical tissues from AIMAH, PPNAD and DAHCD respectively. There were no differences between GIPR and LHCGR expressions in all tissues studied. CONCLUSIONS: GIPR and LHCGR overexpression were not identified in the studied cases, thus suggesting that this molecular mechanism is not involved in adrenocortical hyperplasia in our patients.

OBJETIVO: Analisar a expressão aberrante do GIPR e do LHCGR em diferentes formas de hiperplasias adrenocorticais: hiperplasia adrenal macronodular independente de ACTH (AIMAH), doença adrenocortical nodular pigmentada primária (PPNAD) e hiperplasia adrenal difusa secundária à doença de Cushing (DAHCD). MÉTODOS: Quantificou-se por PCR em tempo real a expressão desses receptores em 20 pacientes: sete com AIMAH, cinco com PPNAD e oito com DAHCD. Adrenais normais foram utilizadas como controle e a expressão relativa desses receptores foi comparada à expressão da β-actina. RESULTADOS: A expressão desses receptores foi demonstrada em todos os tecidos estudados. A mediana da expressão do GIPR e do LHCGR foi de 1,6; 0,4; 0,5 e de 1,3; 0,9; 1,0 nos tecidos dos pacientes com AIMAH, PPNAD e DAHCD, respectivamente. Não houve diferença significativa na expressão desses receptores nos tecidos estudados. CONCLUSÕES: Hiperexpressão do GIPR e do LHCGR não foi observada, sugerindo que esse mecanismo não está envolvido na patogênese molecular da hiperplasia adrenal nesses pacientes.

Policitemia vera: relato de caso / Polycythemia vera: case report

A policitemia vera (PV) é um transtorno mieloproliferativo das células hematopoiéticas, caracterizada poruma produção anormal e acentuada de eritrócitos, leucócitos e plaquetas. É uma doença rara, com uma incidênciade 2,3/100.000 pessoas por ano. Apresentamos um relato de caso de uma paciente de 45 anos com sintomas,sinais e achados sugestivos de policitemia vera.

The polycythemia vera is a myeloproliferative disturb from haematopoietic cells characterized by abnormal and overstated production of erythrocytes, leukocytes and platelets. It is a rare disease with an incidenceof 2.3/100.000 people per year. We present a case report of a 45 years old patient with symptoms, signs andsuggestive results of polycythemia vera.

Cushing's syndrome secondary to ACTH-Independent macronodular adrenal hyperplasia

ACTH-Independent macronodular adrenal hyperplasia (AIMAH) is a rare cause of endogenous Cushing's syndrome (CS), in which clinical features usually become apparent only after several decades of life. This form of adrenal hyperplasia typically produces excess cortisol with overt or subclinical CS, but concurrent secretion of mineralocorticoids or sexual steroids can also occur. The diagnosis is suspected by bilateral adrenal nodules larger than 1 cm on incidental imaging studies or following the demonstration of ACTH-independent hormonal hypersecretion. The pathophysiology of this entity is heterogeneous and has been intensely explored in recent years. Several G-protein coupled receptors aberrantly expressed in the adrenal cortex have been implicated in the regulation of steroidogenesis and in the initial cell proliferation in AIMAH. Several familial cases of AIMAH have been recently described with the same pattern of aberrant hormone receptors in all affected members of the family. It is probable that additional somatic genetic events related to cell cycle regulation, adhesion and transcription factors occur in addition over time in the various nodules; other mechanisms, as Gsp or ACTH receptor mutations and paracrine adrenal hormonal secretion have been rarely identified as the molecular mechanism in some cases. When systematically screened, most patients with AIMAH exhibit an in vivo aberrant cortisol response to one or various ligands suggesting the presence of aberrant adrenal receptors. The identification of these receptors creates the possibility of a specific pharmacological treatment isolated or associated with adrenalectomy.

A hiperplasia adrenal macronodular independente de ACTH (AIMAH) é uma causa rara de síndrome de Cushing (SC) endógena, na qual alguns aspectos clínicos só se tornam evidentes depois de várias décadas de vida. Esta forma de hiperplasia adrenal caracteristicamente produz excesso de cortisol resultando na síndrome de Cushing franca ou subclínica, embora a secreção concomitante de mineralocorticóide, estrógeno e andrógenos também possa ocorrer. A suspeita diagnóstica é feita pela presença de nódulos adrenais bilaterais maiores que 1 cm, como achado incidental em exames de imagem ou pela demonstração de hipersecreção hormonal independente de ACTH. A fisiopatologia desta doença é heterogênea e tem sido intensamente estudada nos últimos anos. Vários receptores acoplados à proteína G, com expressão aberrante no córtex adrenal, têm sido implicados na regulação da esteroidogênese e no início da proliferação celular que ocorre na AIMAH. Diversos casos familiais de AIMAH foram recentemente descritos, e um mesmo padrão de expressão anormal dos receptores aberrantes foi observado em todos os membros afetados das famílias investigadas. Ao longo do tempo, é provável que ocorram, nos nódulos, eventos genéticos adicionais relacionados à regulação do ciclo celular, adesão e fatores de transcrição. Outros mecanismos moleculares, como mutações nos genes da proteína Gsa e do receptor de ACTH, ou secreção hormonal parácrina na adrenal, têm sido raramente identificados em alguns casos. A maioria dos pacientes com AIMAH, quando sistematicamente investigados, desenvolve uma produção anormal de cortisol em resposta a vários ligantes, sugerindo a presença de receptores adrenais aberrantes. A identificação destes receptores cria a possibilidade para um tratamento farmacológico específico isolado ou associado à adrenalectomia.

Utility of galectin 3 expression in thyroid aspirates as a diagnostic marker in differentiating benign from malignant thyroid neoplasms.

Galectin-3 is a 31kD beta-galactoside binding lectin, which is known to be expressed in various neoplasms including thyroid tumors. This study was conducted to study the role of galectin-3 in differentiating benign from malignant thyroid nodules onfine needle aspirates (FNAC). Galectin-3 immuocytochemistry was performed in 70 cases with adequate smears. The cytology diagnosis of these cases was: papillary carcinoma (25), follicular neoplasm (16), adenomatous goiter (20), hyperplastic nodule (5), medullary carcinoma (5) and anaplastic carcinoma (1). Galectin-3 positivity was seen in 80% of papillary carcinomas, 37.5% offollicular neoplasms and in 60% of benign nodules. The single case of anaplastic carcinoma was positive but all the cases of medullary carcinoma were negativefor galectin-3. Three of thefollicular neoplasms that were diagnosed on histology as carcinoma were positive on cytology and one case offollicular adenoma was also positive. Our study shows that galectin-3 is strongly expressed in smears of papillary carcinoma. However, since it is also expressed in a variety of benign lesions, its role as a pre-surgical markerfor differentiating benignfrom malignant thyroid nodules is limited.

p53 immunostaining pattern in Brazilian patients with hepatocellular carcinoma

O carcinoma hepatocelular (CHC) é um importante tipo de câncer relacionado etiologicamente a alguns vírus, carcinógenos químicos e outros fatores ambientais que causam danos crônicos ao fígado em humanos. A freqüência de mutação do gene p53 em CHC é altamente heterogênea (0-52 por cento) nos diversos países. OBJETIVO: O objetivo deste estudo foi determinar, imuno-histologicamente, a freqüência da expressão anômala de p53 em CHCs em pacientes cirróticos versus não-cirróticos, bem como em displasia hepática e hiperplasia adenomatosa. Para isso, foram estudados 84 pacientes com carcinoma hepatocelular ou cirrose. RESULTADOS: Foram detectadas expressões do p53 alterado em 58,3 por cento dos pacientes com CHC graus III-IV, contrastando com os 22,2 por cento dos pacientes com CHC graus I-II (p = 0,02). Áreas não tumorais, tanto nas proximidades do CHC como nos 30 casos de cirrose não mostraram expressão nuclear alterada do p53, mesmo nas displasias ou hiperplasias adenomatosas. Quando se considerou HBV, HCV ou alcoolismo nos casos estudados, não se encontrou diferença significativa. CONCLUSÃO: A elevada freqüência de imuno-expressão de p53 nesta população é próxima à relatada na China e África, tornando necessárias outras pesquisas para explicar as diferenças com os CHC estudados na Europa e na América do Norte.

E-cadherin and Cytokeratin Subtype Profiling in Effusion Cytology

Diagnostic utility of E-cadherin (E-CD) and cytokeratin (CK) subtype profiling in effusion cytology was investigated, employing immunocytochemistry on cellblock sections available from 211 metastatic carcinomas (MC), 6 mesotheliomas and 73 reactive mesothelial hyperplasias (MH). E-CD and monoclonal carcinoembryonic anti-gen (mCEA) stained 85% (120/141) and 65% (138/211) of MC, respectively. E-CD staining of MC was frequently heterogeneous (76/120) and absent in all anaplastic carcinomas (0/2). E-CD stained none (0/57) of MH while mCEA and epithelial membrane antigen (EMA) stained 12% (9/73) and 32% (16/32) of MH, respectively. Of 6 mesotheliomas, E-CD focally stained in 2 while mCEA stained none and EMA stained all. CK20 and CK17 stained none of MH or mesotheliomas. CK20 stained 15% of MC and CK 17 stained 22% of MC. CK5/6 and high molecular weight CK stained all mesotheliomas, 56% and 88% of MH, 26% and 39% of MC, respectively. MC showed predominant CK7+/20-expression, with the exceptions of MC from mucinous type of colon/rectum and ovary showing predominant CK20 positive. E-CD may be a useful positive marker for MC in effusion cytology, although it may focally stain in some mesotheliomas. Any positive staining for CK20 of MC suggests MC from the gastrointestinal tract or ovary among others.

Angiotensin II stimulates proliferation of adventitial fibroblasts cultured from rat aortic explants

It has been proposed that the local renin-angiotensin system is activated in the adventitia after vascular injury. However, the physiological role of Angiotensin II (Ang II) in the adventitia has not been studied at a cellular level. This study was designed to assess the role of Ang II in the growth response of cultured adventitial fibroblasts (AFs). Adventitial explants of the rat thoracic aorta showed outgrowth of AFs within 5-7 days. Ang II caused hyperplastic response of AF cultures. The Ang II-induced mitogenic response of AFs was mediated primarily by the AT1 receptor. Ang II caused a rapid induction of immediate early genes (c-fos, c-myc and jun B). Induction of c-fos expression was fully blocked by an AT1 receptor antagonist but not by an AT2 receptor antagonist. Epidermal growth factor (EGF), platelet-derived growth factor-BB (PDGF-BB) and basic fibroblast growth factor (bFGF) induced DNA synthesis in AFs. Co-stimulation of AFs with the growth factors and Ang II potentiated the incorporation of 3H-thymidine into DNA. Results from this study indicate that Ang II causes mitogenesis of AFs via AT1 receptor stimulation and potentiates the responses to other mitogens. These data suggest that the Ang II may play an important role in regulating AF function during vascular remodeling following arterial injury.

Caracterizaçäo da ligaçäo do 125 ITSH ao seu receptor em hiperplasias tiroidianas hipocaptantes / Caracterization of the binding of 125 ITSH to its receptor in hypocaptant thyroid hyperplasias

Acredita-se que o desarranjo metabólico celular existente no bócio simples possa ser conseqüência de um desequilíbrio das açöes do TSH sobre a glândula tiróide. Já que a ligaçäo do TSH ao seu receptor é a primeira etapa na gênese de seus efeitos biológicos a nível da célula alvo, objetivou-se na presente investigaçäo caracterizar a ligagçäo de 125 ITSH ao seu receptor em fragmentos de tiróides humanas de pacientes portadores de nódulo "frio" e anatomopatológico de hiperplasia folicular benigna. Os tecidos foram obtidos no ato cirúrgico e imediatamente armazenados em nitrogênio líquido. Após determinaçäo das condiçöes ótimas de incubaçäo (duraçäo, pH do meio e concentraçäo protéica) e empregando-se a análise de Scatchard, verificou-se näo haver diferenças significativas quanto à capacidade de ligaçäo dos receptores de TSH, quando comparada à do tecido normal paranodular. Por outro lado, observou-se nítida diminuiçäo da constante de dissociaçäo desses receptores, indicando maior afinidade pelo TSH. Sabe-se que o iodo intracelular pode interferir nas açöes do TSH sobre a célula folicular tiroidiana. Supöe-se que isto seja decorrente de um efeito de ligaçäo do TSH ao seu receptor. Devido à sua incapacidade de organificaçäo do iodo, os módulos "frios" apresentam diminuiçäo do conteúdo de iodo intracelular. Assim, acredita-se que as alteraçöes encontradas no presente estudo sejam conseqüência do baixo conteúdo de iodo da célula folicular hiperplásica