RESUMO
OBJECTIVES: To evaluate the diagnostic yield of endoscopic ultrasonography in loco-regional staging of gastric cancer in our medium and to determine the impact of this technique on later therapeutic management. MATERIAL AND METHODS: This is a retrospective study carried out on patients histologically diagnosed with gastric adenocarcinoma who had been referred for endoscopic ultrasonographic examination. The technique results were compared with those obtained from surgical samples and/or from exploratory laparoscopy- laparotomy. We compared the initial therapeutic decision based on conventional diagnostic techniques with the final therapeutic management based on the endoscopic ultrasonography results. RESULTS: Forty-six patients with gastric adenocarcinoma were included in the study (a reference exploration was available in 36 cases). Diagnostic precision was 70% in stage T, while in stages T1, T2, T3 y T4 was 100, 38, 82, and 100%, respectively. The sensitivity and specificity to differentiate T1-2 from T3-4 was 94 and 85%, respectively. We could not identify factors associated with obtaining a correct diagnosis in staging T. Diagnostic precision was 72% for stage N (N0: 58%; Nx 88%). The presence of free perigastric fluid was identified in 7 cases; the presence of peritoneal carcinomatosis was later confirmed in 5 of these. The result of endoscopic ultrasonography led to a modification in the subsequent therapeutic management in 13 patients (28%). CONCLUSIONS: Endoscopic ultrasonography is a useful technique for loco-regional staging of gastric adenocarcinoma, which may have important implications in the therapeutic management of these patients.
Assuntos
Endossonografia , Cuidados Pré-Operatórios , Neoplasias Gástricas/diagnóstico por imagem , Neoplasias Gástricas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Retrospectivos , Neoplasias Gástricas/terapiaRESUMO
OBJECTIVE: the objective of our study was to evaluate the usefulness of endoscopic ultrasonography (EUS) for the study of the common bile duct in patients diagnosed with acute biliary pancreatitis, and to establish clinical and laboratory factors related to this technique. MATERIALS AND METHODS: seventy-three consecutive patients with acute biliary pancreatitis were included in the study (31 males and 42 females with a mean age of 64 +/- 15) who were admitted to our department for biliopancreatic EUS. In all patients the technique was followed by ERCP with sphincterotomy, and endoscopy to remove stones when endoscopy revealed choledocholithiasis. RESULTS: mean time from admission to echoendoscopy was 7 +/- 6 days. In 18 patients (24%) the presence of choledocholithiasis was revealed by EUS, and in 17 a sphincterotomy was performed. Choledocholithiasis was more frequent in patients with common bile duct dilation (55 vs. 14%; p < 0.05). Thirteen patients (18%) showed severe acute pancreatitis. Fourteen (19%) showed complications related to acute pancreatitis, and one patient died. Four patients had a new episode of acute pancreatitis. No significant difference was seen in the percentage of complications between patients treated conservatively and patients with choledocholithiasis treated with endoscopic sphincterotomy (18 vs. 22%; p > 0.05). No difference was also detected for the subgroup of patients with severe acute pancreatitis (45 vs. 55%; p > 0.05). CONCLUSIONS: EUS is a useful technique for the selection of patients with acute biliary pancreatitis who may benefit from endoscopic sphincterotomy.
Assuntos
Coledocolitíase/complicações , Coledocolitíase/diagnóstico por imagem , Ducto Colédoco/diagnóstico por imagem , Endossonografia , Pancreatite/diagnóstico por imagem , Pancreatite/etiologia , Doença Aguda , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
INTRODUCTION: Autoimmune pancreatitis is a kind of chronic pancreatitis characterized by the presence of lymphoplasmacytic infiltration and severely elevated serum IgG and IgG4, which has been associated to many extrapancreatic lesions and other autoimmune disorders, leading to the theory of an autoimmune mechanism involved in the pathogenesis of this disease. CASE REPORT: We report the case of a man who simultaneously presented with autoimmune pancreatitis associated with retroperitonal fibrosis, and a lesion of the extrapancreatic bile duct, with total response to corticosteroid treatment for 4 months and absence of recurrence after 24 months of follow-up. DISCUSSION: Autoimmune pancreatitis is a kind of chronic pancreatitis that is probably a part of a systemic autoimmune disease, with retroperitoneal fibrosis and extrapancreatic bile duct lesion being the most commonly associated extrapancreatic lesions. A correct diagnosis and early treatment of this disease may aid in the total resolution of lesions, especially in cases with a low activity grade.
Assuntos
Doenças Autoimunes/complicações , Pancreatite/complicações , Fibrose Retroperitoneal/complicações , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/uso terapêutico , Doenças Autoimunes/diagnóstico , Doenças Autoimunes/diagnóstico por imagem , Doenças Autoimunes/tratamento farmacológico , Seguimentos , Glucocorticoides/administração & dosagem , Glucocorticoides/uso terapêutico , Humanos , Masculino , Metilprednisolona/administração & dosagem , Metilprednisolona/uso terapêutico , Pessoa de Meia-Idade , Pancreatite/diagnóstico , Pancreatite/diagnóstico por imagem , Pancreatite/tratamento farmacológico , Radiografia Abdominal , Fibrose Retroperitoneal/diagnóstico , Fibrose Retroperitoneal/diagnóstico por imagem , Fatores de Tempo , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
OBJECTIVE: The aim of this study was to evaluate in our healthcare area the clinical, ultrasonographic, and evolutionary features of patients with chronic liver disease and angioma-like liver lesions on ultrasonography. MATERIALS AND METHODS: We conducted a retrospective study amongst patients seen at the Ultrasonography Unit, Gastroenterology Department between January 2000 and June 2004. Included in the study were patients that presented with clinical and/or laboratory complaints consistent with chronic liver disease of any etiology, and those in which abdominal ultrasounds revealed the existence of at least one angioma-like liver lesion. All relevant epidemiological, clinical, ultrasonographic, and evolutionary data were carefully collected and recorded. RESULTS: In the course of our study, 58 patients were diagnosed with chronic liver disease and angioma-like liver lesions, of which 13 showed clinical, laboratory, ultrasonographic, and/or histological signs of liver cirrhosis. In 50% of patients these lesions were less than 10 mm in diameter, and in most cases were located in the right hepatic lobe. During an average follow-up period of 35 months (6-168 months) we verified that, in two patients, these lesions, initially interpreted as angiomas were in fact malignancies (one hepatocellular carcinoma and one metastatic adenocarcinoma of the gallbladder). In both cases, the patients were cirrhotic. Thus, our study revealed that 15% of lesions found in cirrhotic patients initially interpreted as angiomas were actually malignant. CONCLUSIONS: Our study revealed that, in patients with chronic liver disease, particularly in cirrhotic patients, a considerable percentage of ultrasonographic lesions originally interpreted as angiomas are in fact malignant tumors.
Assuntos
Hemangioma/diagnóstico por imagem , Cirrose Hepática/diagnóstico por imagem , Neoplasias Hepáticas/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Doença Crônica , Feminino , Humanos , Hepatopatias/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , UltrassonografiaRESUMO
Triiodothyronine (T3) exerts most of its effect through nuclear thyroid hormone receptors (TR) which bind mainly as heterodimers with retinoid-X receptors (RXR) to thyroid hormone response elements (TRE) in target genes. It is well known that the synergistic interaction of T3 and glucocorticoids has a role on the synthesis of growth hormone in rat pituitary cell lines and in the T3-induced metamorphosis in amphibians. Glucocorticoids increased mRNAs of T3-regulated hepatic genes. Our laboratory reported increased specific metabolic actions of T3 in rat liver by Dexamethasone (Dex) through a mechanism involving an up-regulation of the maximal binding capacity of TR. In this study we further explored the participation of TR in the molecular mechanism of the Dex-induced increase on liver T3-specific metabolic action. Dex administration to adrenalectomized rats induced an increase of liver TRbeta1 protein and mRNA. Nuclear run-on assay revealed that Dex up-regulated the TR gene transcriptional rate. Transfection assay in COS-7 cells indicated that Dex increased the transcriptional activity of the TRbeta1 promoter. Electrophoretic mobility shift assay demonstrated that Dex induced the binding of additional proteins related to or neighboring the DNA sequence of a glucocorticoid receptor (GR) binding (GRE) half-site in the TRbeta1 promoter. Evidences for an interaction of GR on the TRbeta1 promoter have been obtained. Moreover, the specificity of the GR binding to GRE was determined not only by the GRE DNA sequence, but also by the interaction of the GR with other transacting factors bound to sequences flanking the GRE.
Assuntos
Anti-Inflamatórios/farmacologia , Dexametasona/farmacologia , Fígado/efeitos dos fármacos , Biossíntese de Proteínas/efeitos dos fármacos , Receptores beta dos Hormônios Tireóideos/genética , Transcrição Gênica/efeitos dos fármacos , Adrenalectomia , Animais , Sequência de Bases , Células COS , Chlorocebus aethiops , Fígado/metabolismo , Masculino , Dados de Sequência Molecular , Ligação Proteica/efeitos dos fármacos , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Receptores de Glucocorticoides/efeitos dos fármacos , Receptores de Glucocorticoides/metabolismo , Receptores beta dos Hormônios Tireóideos/metabolismoRESUMO
BACKGROUND: Patients with inflammatory bowel disease may suffer one or more extraintestinal manifestations during the course of their condition, these being more frequent in Crohn s disease. The aim of our study was to evaluate the prevalence of extraintestinal manifestations in patients with Crohn s disease in our healthcare area, and to assess the relationship between its presence and diverse clinical-evolutionary variables. MATERIAL AND METHODS: Extraintestinal manifestations in 157 patients diagnosed with Crohn s disease in our center were retrospectively studied. The clinical-evolutionary characteristics of this population were compared with respect to the presence or absence of different extraintestinal manifestations. RESULTS: Seventy-two patients (46%) presented at least with one extraintestinal manifestation. Thirty-one percent were colitis-related manifestations (22% rheumatologic, 13% muco-cutaneous, 4% ophthalmologic), 11% cholelithiasis, 8% nephrolithiasis, 3% thromboembolic illness, and other manifestations were less frequent. Fourteen percent presented with more than one extraintestinal manifestation. Rheumatologic and muco-cutaneous manifestations were significantly more frequent in patients with disease confined to the colon. Cholelithiasis was significantly associated to those over 40 and also to males. Nephrolithiasis was also significantly associated to those over 40, and thromboembolic illness was linked to females. CONCLUSIONS: forty-six percent of patients with Crohn s disease presented at least with one extraintestinal manifestation. Thirty-one percent presented with colitis-related manifestations, rheumatologic and muco-cutaneous manifestations being the most frequent, whereas hepatic manifestations were infrequent. Rheumatologic and muco-cutaneous manifestations were more frequent in patients with disease confined to the colon.
Assuntos
Doença de Crohn/diagnóstico , Doenças Reumáticas/etiologia , Dermatopatias/etiologia , Adulto , Idoso , Doença de Crohn/complicações , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Doenças Reumáticas/epidemiologia , Dermatopatias/epidemiologiaRESUMO
Several biochemical and functional modifications demonstrated in goitrous tissues could reflect the effect of goitrogenic factors. Growth-enhancing agents, including TSH itself, have been involved in goitrogenesis. To study comparatively the variation patterns of some TSH-dependent enzymes within single goitrous tissues, we measured the activities of peroxidase (TPO), NADPH-cytochrome-c (cyt-c) reductase, and monoamine oxidase (MAO) in tissues from cold follicular adenoma and multinodular goiter. Iodide transport and organification were also evaluated. Perinodular and necropsy tissues were used as controls. The mean TPO activity measured by guaiacol as well as triiodide assays was significantly increased in multinodular goiter, whereas a nonsignificant increment was observed in cold adenoma. NADPH-cyt-c reductase and MAO were markedly increased in the two types of pathological tissues. The individual activities of the three enzymes showed dissimilar modifications within single samples and among different tissues. There was no correlation in the activities of the enzymes within single specimens from cold adenoma and multinodular goiter, except for MAO and NADPH-cyt-c reductase in multinodular goiter, for which a significant correlation was obtained. In this tissue, MAO and TPO measured by guaiacol assay were weakly correlated. TPO activity evaluated by guaiacol oxidation was correlated with that measured by triiodide formation in cold adenoma, but not in multinodular goiter. The mean iodide organification values assayed by iodotyrosine formation in the absence of exogenous H2O2 in particulate fractions from cold adenoma and multinodular goiter were within the normal range. A reduced iodide transport, evaluated as the thyroid/medium ratio, was observed in slices from these tissues. The dissociation of the three enzyme activities in single specimens from cold adenoma and multinodular goiter along with the reduced iodide transport in these tissues support the hypothesis that factors other than TSH or with TSH-like effects could be involved in the abnormal thyroid growth.
Assuntos
Adenoma/enzimologia , Bócio Nodular/enzimologia , Iodetos/metabolismo , Neoplasias da Glândula Tireoide/enzimologia , Tireotropina/farmacologia , Transporte Biológico , DNA/metabolismo , Humanos , Iodeto Peroxidase/metabolismo , Monoaminoxidase/metabolismo , NADPH-Ferri-Hemoproteína Redutase/metabolismo , Glândula Tireoide/enzimologiaRESUMO
The characteristics and regulation of monoamine oxidase (MAO) were studied in rat thyroid tissue. A measured Michaelis constant (Km) value of 102 mumol/l was similar to the Km values found in other tissues. Maximal velocity (Vmax) was 1.028 nmol/mg protein per min. It is known that MAO is present as two isoenzymes, A and B, which are sensitive to clorgyline and deprenyl respectively. The in-vitro effect of graded concentrations of these selective MAO inhibitors was used to estimate the relative proportion of A and B isoenzymes. Clorgyline strongly decreased thyroid MAO activity at concentrations as low as 1 pmol/l while the effect of deprenyl was observed only at concentrations higher than 10 mumol/l. These results indicated that MAO-A is the main form of the enzyme in the rat thyroid. In-vivo administration of L-thyroxine (5.6-224 nmol/kg) significantly reduced thyroid MAO activity at doses equal to or greater than those which have been reported to inhibit iodine output from the thyroid. Increased TSH levels, induced either by exogenous TSH or methimazole administration, resulted in a significant increase in thyroid MAO activity. Theophylline, a phosphodiesterase inhibitor and dibutyryl cyclic AMP were also able to stimulate MAO activity when administered in vivo. Iodide organification (protein-bound 131I) in vivo as well as the relative proportion of the different thyroid iodo-compounds were not affected in animals with reduced or increased thyroid MAO activity induced by clorgyline or theophylline respectively. It was concluded that rat thyroid MAO activity is under the influence of TSH.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Iodetos/metabolismo , Isoenzimas/metabolismo , Monoaminoxidase/metabolismo , Glândula Tireoide/enzimologia , Tireotropina/fisiologia , Animais , Bucladesina/farmacologia , Clorgilina/farmacologia , Depressão Química , Masculino , Metimazol/farmacologia , Ratos , Ratos Endogâmicos , Selegilina/farmacologia , Teofilina/farmacologia , Glândula Tireoide/efeitos dos fármacos , Glândula Tireoide/metabolismo , Tiroxina/farmacologiaRESUMO
The present work was addressed to study a possible relationship between monoamine oxidase (MAO) and the thyroid iodide transport mechanism. Normal rats treated with clorgyline (a selective MAO-A inhibitor) or tranylcypromine (a non-selective MAO inhibitor) showed a significantly diminished thyroid MAO activity, while deprenyl and pargyline (MAO-B inhibitors) did not modify the thyroidal enzyme activity with respect to the control group. Under these conditions, in vivo iodide transport was reduced both by clorgyline and tranylcypromine administration whereas it remained unchanged after treatment with MAO-B inhibitors. The effect of MAO inhibitors on thyroid MAO activity and in vivo iodide transport was also evaluated in rats treated with exogenous thyrotrophin (TSH) after endogenous TSH secretion blockade produced by T4 administration. In this condition, thyroid MAO activity was significantly lowered by clorgyline and was not modified by deprenyl. In contrast to the results observed in normal rats, in vivo iodide transport in TSH-treated rats remained unaltered after treatment either with clorgyline or deprenyl. MAO activity evaluated in bovine thyroid follicles in primary culture was highly sensitive to low concentrations of clorgyline (< 10 nmol/l) and relatively insensitive to deprenyl, a finding that indicates a predominance of the MAO-A isoform in the follicular cells in culture. When clorgyline (0.1 and 1 mumol/l) or deprenyl (1 mumol/l) were added to the culture medium, no modifications in the active transport of iodide were observed. These results indicate the absence of a direct linkage between thyroid MAO activity and the active iodide transport.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Iodetos/metabolismo , Inibidores da Monoaminoxidase/farmacologia , Monoaminoxidase/metabolismo , Glândula Tireoide/metabolismo , Animais , Transporte Biológico/efeitos dos fármacos , Clorgilina/farmacologia , Masculino , Técnicas de Cultura de Órgãos , Pargilina/farmacologia , Ratos , Ratos Wistar , Selegilina/farmacologia , Glândula Tireoide/efeitos dos fármacos , Tranilcipromina/farmacologiaRESUMO
The effects of the tri-iodothyronine (T(3)) secreted by thyroid cells on the growth of the thyrocyte are poorly known. In this study we analyzed the effects of T(3) on the proliferation of bovine thyroid follicles in primary culture previously depleted of endogenous T(3). Cellular deoxiribonucleic acid (DNA) synthesis, determined by [(3)H]thymidine incorporation, was stimulated by T(3) (0.1-5.0 nM) for 24 h in a concentration-dependent fashion with a maximal effect at 1.0 nM T(3) (P<0.01). This T(3) action was time-dependent when assayed from 12 to 72 h. The induction of mitogenic activity was corroborated by the increase in proliferating cell nuclear antigen (PCNA) measured by Western blot analysis. PCNA increased after treatment with T(3) (0.1-5.0 nM) in a concentration-dependent manner. Since T(3) modifies the activity of growth factors whose actions are mainly mediated by tyrosine kinase (TK) activation in diverse cellular types, we assayed the effects of genistein, a general TK inhibitor, and tyrphostin A25, a specific epidermal growth factor (EGF)-receptor (EGFR)-dependent TK activity inhibitor, on the proliferative effects of T(3). The T(3)-induced [(3)H]thymidine incorporation was inhibited by both agents in a concentration-dependent manner. A significant increase in the total TK activity measured in cellular protein extracts was induced by 0.5 and 1.0 nM T(3) (P<0.001). Tyrosine phosphorylation of the EGFR was also stimulated by T(3) (P<0.001) with no change in the EGFR expression as determined by Western blot analysis. Both, the T(3)-stimulated [(3)H]thymidine incorporation and the TK activity were inhibited by a anti-mouse EGF antibody. These results lead us to propose that T(3) could operate as a proliferative agent in bovine thyroid cells through a mechanism involving an autocrine/paracrine EGF/EGFR-dependent regulation.
Assuntos
Receptores ErbB/metabolismo , Glândula Tireoide/metabolismo , Tri-Iodotironina/farmacologia , Análise de Variância , Animais , Biomarcadores/análise , Western Blotting , Bovinos , Divisão Celular/efeitos dos fármacos , Células Cultivadas , DNA/biossíntese , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/farmacologia , Receptores ErbB/antagonistas & inibidores , Genisteína/farmacologia , Fosforilação , Antígeno Nuclear de Célula em Proliferação/análise , Proteínas Tirosina Quinases/metabolismo , Estimulação Química , Timidina Quinase/antagonistas & inibidores , Glândula Tireoide/efeitos dos fármacos , Tirfostinas/farmacologiaRESUMO
Tri-iodothyronine (T3) is known to be involved in the regulation of the growth hormone (GH)-insulin-like growth factor I (IGF-I) axis. In previous studies we demonstrated that IGF-I and GH reduced the metabolic response to T3 measured as the activity of two T3-dependent enzymes, mitochondrial alpha-glycerophosphate dehydrogenase (alpha-GPD) and cytosolic malic enzyme (ME) in cultured rat liver cells. In this study we analysed in vivo the effect of IGF-I administered to rats on the activity of alpha-GPD and ME. IGF-I (240 micrograms/100 g body weight (BW) every 12 h for 48 h) significantly diminished alpha-GPD (P < 0.01) and ME (P < 0.05) activities. Serum basal glucose concentration was not significantly modified 12 h after the administration of recombinant human IGF-I (240 and 480 micrograms/100 g BW every 12 h for 48 h). Under similar conditions, no significant change in serum total thyroxine (TT4) concentration was observed, although free thyroxine (FT4) was diminished (P < 0.02) and total T3 (TT3) was increased (P < 0.03). To explore the participation of the nuclear thyroid hormone receptor (THR) in the mechanism of IGF-I action we measured the maximal binding capacity and the affinity constant (Ka) of THR by Scatchard analysis, and concentrations of messenger RNAs (mRNAs) that code for the isoforms of THR present in the liver (beta 1, alpha 1 and alpha 2) by Northern blot. IGF-I (240 micrograms/100 g BW every 12 h for 48 h) significantly reduced maximal binding capacity to 37% of the control value (P < 0.01) without changes in the Ka. beta 1, alpha 1 and alpha 2 THR mRNAs were significantly reduced (P < 0.01) by 120-480 micrograms/100 g BW IGF-I administration every 12 h for 48 h. Time-course studies indicated that this effect was obtained 12 h after the administration of 240 micrograms/100 g BW IGF-I (P < 0.05). These results indicate that IGF-I administration to rats diminishes the metabolic thyroid hormone action in the liver by a mechanism that involves, at least in part, a reduction in the number of THRs and in their level of expression.
Assuntos
Fator de Crescimento Insulin-Like I/farmacologia , Fígado/metabolismo , Receptores dos Hormônios Tireóideos/metabolismo , Hormônios Tireóideos/metabolismo , Animais , Células Cultivadas , Citosol/efeitos dos fármacos , Citosol/enzimologia , Retroalimentação , Glicerolfosfato Desidrogenase/metabolismo , Fígado/efeitos dos fármacos , Malato Desidrogenase/metabolismo , Masculino , Mitocôndrias Hepáticas/efeitos dos fármacos , Mitocôndrias Hepáticas/enzimologia , Ligação Proteica , Ratos , Ratos Wistar , Tiroxina/metabolismo , Tri-Iodotironina/metabolismoRESUMO
Triiodothyronine (T3) is involved in the regulation of the growth hormone-insulin-like growth factor I (GH-IGF-I) axis. In this study we investigated the effect of GH and IGF-I on the metabolic response of T3 in target tissues by evaluating the activity of two T3-dependent liver enzymes: mitochondrial alpha-glycerophosphate dehydrogenase (alpha-GPD) and cytosolic malic enzyme (ME) in rat hepatocytes in primary culture. Growth hormone (35 nmol/l) as well as IGF-I (0.5 mumol/l) reduced alpha-GPD and ME activities (p < 0.01) compared to the control group. Timecourse studies indicated that IGF-I (1.5 mumol/l) significantly decreased alpha-GPD and ME activities (P < 0.01) after 24 h, whereas the effect of GH (35 nmol/l) was recorded only after 36 h (p < 0.01). This delayed effect of GH compared to IGF-I suggested the possibility that the effect of GH could be mediated by IGF-I synthesis. To test this hypothesis, the effect of GH on the two enzyme activities was studied in the presence of anti-IGF-I antibodies. A gradual recovery of alpha-GPD and ME activities (p < 0.01) was observed in the presence of GH (35 nmol/l) plus increasing concentrations of anti-IGF-I antiserum. The maximal alpha-GPD and ME activities attained after the incubation of the liver cells with 1 mumol/l T3, a concentration high enough to fully saturate the nuclear T3 receptors for 24 h, were lowered significantly by 1.0 mumol/l IGF-I (p < 0.01). This finding suggests that the IGF-I effect might be independent of the saturation of the nuclear T3 receptors. In conclusion, in cultured rat hepatocytes, GH and IGF-I reduced the metabolic response of T3 evaluated by two liver T3-dependent enzyme activities. The effect of GH was mediated at least in part by IGF-I.
Assuntos
Glicerolfosfato Desidrogenase/metabolismo , Hormônio do Crescimento/farmacologia , Fator de Crescimento Insulin-Like I/farmacologia , Fígado/enzimologia , Malato Desidrogenase/metabolismo , Tri-Iodotironina/farmacologia , Animais , Células Cultivadas , Citosol/enzimologia , Inibidores Enzimáticos/farmacologia , Soros Imunes/farmacologia , Fator de Crescimento Insulin-Like I/antagonistas & inibidores , Fator de Crescimento Insulin-Like I/imunologia , Fígado/efeitos dos fármacos , Masculino , Mitocôndrias Hepáticas/enzimologia , Ratos , Ratos WistarRESUMO
The involvement of atrial natriuretic peptide (ANP) in the regulation of thyroid gland is supported by the presence of high-affinity ANP receptors and the identification of the peptide in thyroid follicular cells. The aim of this work was to study the action of ANP on parameters of thyroid hormone biosynthesis and analyze the intracellular mechanism of the ANP action in cultured bovine thyroid follicles. The addition of ANP (0.1-10 nM) to the culture medium for 24 h inhibited the TSH (thyroid-stimulating hormone)-stimulated iodide uptake with a maximal inhibition at 1 nM ANP. When thyrocytes were incubated with 10 nM ANP the inhibitory effect slightly increased from 24 to 72 h. Thyroglobulin (Tg) mRNA expression was reduced by 1 and 10 nM ANP. After 24 h of treatment with the cGMP analogue, N(2),2'-O-dibutyrylguanosine 3':5'-cyclic monophosphate [(Bu)(2)cGMP] (0.1 and 1 mM), an inhibition of iodide uptake and Tg mRNA expression was obtained, evidencing a cGMP-mediated inhibitory signal in the thyroid cell. A reduction of the cAMP production was induced by incubation of thyroid follicles with 1 and 10 nM ANP for 24 h. Under a similar treatment the cGMP accumulation was increased only by 10 nM ANP. The inhibitory effect of ANP on Tg mRNA level was reverted in the presence of pertussis toxin, an inhibitor of the G(i)-protein-mediated reduction of the adenylate cyclase activity. These results indicate an inhibitory action of ANP on parameters of thyroid hormone biosynthesis. A G(i)-protein-mediated reduction of the cAMP production seems to be the main factor involved in the ANP action although a role of the cGMP pathway should not be discarded specially at high ANP levels.
Assuntos
Fator Natriurético Atrial/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Iodetos/metabolismo , Tireoglobulina/genética , Glândula Tireoide/efeitos dos fármacos , Animais , Transporte Biológico/efeitos dos fármacos , Bovinos , Células Cultivadas , AMP Cíclico/metabolismo , GMP Cíclico/metabolismo , Toxina Pertussis/farmacologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Transdução de Sinais/efeitos dos fármacos , Glândula Tireoide/citologia , Glândula Tireoide/metabolismo , Hormônios Tireóideos/biossínteseRESUMO
To establish biochemical and functional relations during thyroid development, the activity of thyroid peroxidase (TPO), nicotinamide adenine dinucleotide phosphate (NADPH)-cytochrome c reductase and monoamine oxidase (MAO) in a particulate fraction and the iodide transport and organification in slices of bovine fetal thyroid were examined throughout gestation. The cytochemical localization of TPO, H2O2 generating sites and MAO was also studied. Fetal glands were grouped in stages I to V according to increasing developmental features; adult tissues were also analyzed. TPO activity in each of the fetal stages was higher than in the adult; a marked increase was observed in stages IV and V. Iodide transport (T/M) was similar in stages I to V and the adult. Iodide organification in fetal thyroids showed a similar pattern to that of TPO activity. When compared with the adult, at midgestation (stages II to III), a lower iodination coexisted with a higher TPO activity. The activity of NADPH-cytochrome c reductase and MAO, two enzymes previously proposed to participate in thyroid H2O2 generation, did not parallel the level of iodide organification. Cells from stages II to V exhibited a positive cytochemical reaction for TPO in the rough endoplasmic reticulum (RER) and the perinuclear cisternae (PC). In stages IV, V, and adult, TPO was occasionally found in apical vesicles and microvilli, whereas H2O2 was detected within the RER and the PC. MAO reaction was positive in adult, but not in fetal thyroid. These results indicate that a high TPO activity accompanied the onset of the organification process during fetal thyroid development. The level of iodination was associated with the presence of TPO at a proper site rather than to the level of TPO activity. Evidence against a role of NADPH-cytochrome c reductase and MAO in the iodide organification was obtained.
Assuntos
Feto/fisiologia , Glândula Tireoide/embriologia , Animais , Transporte Biológico/fisiologia , Bovinos/embriologia , DNA/metabolismo , Desenvolvimento Embrionário e Fetal/fisiologia , Feto/metabolismo , Histocitoquímica , Peróxido de Hidrogênio/metabolismo , Iodeto Peroxidase/metabolismo , Iodetos/metabolismo , Monoaminoxidase/metabolismo , NADPH-Ferri-Hemoproteína Redutase/metabolismo , Proteínas/metabolismo , Glândula Tireoide/metabolismo , Glândula Tireoide/fisiologiaRESUMO
Nitric oxide (NO) has been proposed as an intracellular signal in the thyroid. The NO effect on function and morphology of bovine thyroid follicles in culture was analyzed by using the NO donors sodium nitroprusside (SNP) and S-nitrosoglutathione (GSNO). Both NO donors induced a concentration-dependent NO release measured by the nitrite accumulation in the culture medium. The SNP (10 to 500 micromol/L) treatment for 24 hours significantly inhibited the uptake, organification and transport of iodide in a concentration-dependent manner. When SNP (50 micromol/L) was withdrawn from the culture medium after 24 hours' incubation, iodide uptake and organification were partially recovered at 24 hours and reached the control value at 48 hours, indicating a reversible effect of SNP. A possible involvement of cyanide in the SNP inhibitory effect was excluded because incubation of follicles with potassium cyanide (KCN) at concentrations estimated to be present in the medium (40 and 80 micromol/L) for 24 hours did not modify iodide uptake and organification. The GSNO (10 to 500 micromol/L) treatment for 24 hours also reduced the iodide uptake, organification and transport in a concentration-dependent manner. A significant inhibition of iodide organification was induced after incubation with 1000 micromol/L of N2, 2'-O-dibutyrylguanosine 3':5'-cyclic monophosphate ([Bu]2cGMP). Morphological evaluation by light microscopy revealed that the incubation with NPS or GSNO (500 micromol/L) produced cellular dispersion with loss of follicular cell aggregates that was evident at 96 hours exposure. Cell viability was not altered by 10-500 micromol/L SNP or GSNO (80% to 85%). We concluded that long-term NO exposure induces functional and morphological modifications compatible with a loss of differentiation in thyroid follicles. These observations further support a role of NO in the regulation of the thyroid function.
Assuntos
Iodetos/metabolismo , Doadores de Óxido Nítrico/farmacologia , Glândula Tireoide/citologia , Glândula Tireoide/efeitos dos fármacos , Animais , Transporte Biológico/efeitos dos fármacos , Bovinos , Células Cultivadas , Meios de Cultura , Dibutiril GMP Cíclico/farmacologia , Glutationa/análogos & derivados , Glutationa/farmacologia , Óxido Nítrico/biossíntese , Nitritos/metabolismo , Nitroprussiato/farmacologia , Compostos Nitrosos/farmacologia , Cianeto de Potássio/farmacologia , S-Nitrosoglutationa , Glândula Tireoide/metabolismoRESUMO
Sequence analysis of the TR beta gene from a patient with the syndrome of resistance to thyroid hormone revealed a novel missense mutation in exon 9, changing thymidine in position 1123 to cytosine. The corresponding amino acid alteration is a substitution of a methionine (ATG) for a threonine (ACG) at codon 313 being the patient heterozygous for the mutation. In contrast, his parents had only the wild-type sequence, suggesting a de novo mutational event.
Assuntos
Mutação Puntual/fisiologia , Receptores dos Hormônios Tireóideos/genética , Síndrome da Resistência aos Hormônios Tireóideos/genética , Criança , DNA/análise , DNA/genética , Éxons , Humanos , Masculino , Metionina/metabolismo , Mutação Puntual/genética , Reação em Cadeia da Polimerase , RNA Antissenso/genética , Treonina/metabolismoRESUMO
Amyloidosis commonly affects the gastrointestinal tract but it rarely causes severe symptoms. We describe here a case of small bowel amyloidosis presenting severe bleeding. The diagnosis was made by histopathological study of the surgical specimen. No other sites of amyloid deposition were found. The only predisposing condition found in this case was a prostate cancer.
Assuntos
Amiloidose/complicações , Duodenopatias/complicações , Hemorragia Gastrointestinal/etiologia , Idoso , Amiloidose/patologia , Amiloidose/cirurgia , Duodenopatias/diagnóstico por imagem , Duodenopatias/cirurgia , Duodeno/diagnóstico por imagem , Duodeno/patologia , Duodeno/cirurgia , Hemorragia Gastrointestinal/patologia , Hemorragia Gastrointestinal/cirurgia , Humanos , Masculino , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
OBJECTIVES: 17ß-oestradiol interacts with growth factors to modulate lactotroph cell population. However, contribution of isoforms of the oestrogen receptor in these activities is not fully understood. In the present study, we have established participation of α and ß oestrogen receptors in effects of 17ß-oestradiol on lactotroph proliferation induced by insulin and shown involvement of the NO/sGC/cGMP pathway. MATERIALS AND METHODS: Cell cultures were prepared from anterior pituitaries of female rats to evaluate lactotroph cell proliferation using bromodeoxyuridine (BrdUrd) detection, protein expression by western blotting and cGMP by enzyme immunoassay. RESULTS: In serum-free conditions, 17ß-oestradiol and α and ß oestrogen receptor agonists (PPT and DPN) failed to increase numbers of lactotroph cells undergoing mitosis. Co-incubation of 17ß-oestradiol/insulin and PPT/insulin significantly decreased lactotroph mitogenic activity promoted by insulin alone. Both ICI 182780 and NOS inhibitors (L-NMMA and L-NAME) induced reversal of the anti-proliferative effect promoted by 17ß-oestradiol/insulin and PPT/insulin. Moreover, 17ß-oestradiol, PPT and insulin increased sGC α1 protein expression and inhibited ß1, whereas co-incubation of 17ß-oestradiol/insulin or PPT/insulin induced increases of the two isoforms α1 and ß1. 17ß-oestradiol and insulin reduced cGMP production, while 17ß-oestradiol/insulin co-incubation increased this cyclic nucleotide. CONCLUSIONS: Our results suggest that 17ß-oestradiol is capable of arresting lactotroph proliferation induced by insulin through ER α with participation of the signalling NO/sGC/cGMP pathway.