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INTRODUCTION: Ghrelin is a 28 amino acid peptide mainly secreted by endocrine cells of the gastric mucosa, which is believed to have a modulating effect on cell growth. OBJECTIVE: To assess the presence of ghrelin and its precursor preproghrelin molecule in endocrine hyperplasias associated with atrophic body gastritis (ABG). MATERIAL AND METHODS: Endoscopic biopsies from 54 patients with ABG were processed for immunohistochemistry and specific antibodies against ghrelin, preproghrelin and chromogranin were applied. We assessed the immunoreactive cells in endocrine hyperplasia from the atrophic mucosa and intestinal and pseudo-antral metaplasia areas. RESULTS: There was ghrelin expression in a variable number of hyperplastic endocrine cells from all patients studied. There was a statistically significant difference in the number of hyperplastic nodules with more than 50 percent immunostained cells for chromogranin and ghrelin and for chromogranin and preproghrelin. The mean number of hyperplastic nodules identified by chromogranin was 8.6 per patient. Most nodules were immunoreactive to ghrelin and preproghrelin. The presence of ghrelin and preproghrelin expression was uncommon in glands showing intestinal metaplasia: four (9.5 percent) and nine (21.4 percent) cases, respectively. In contrast, they were relatively frequent in pseudo-antral metaplasia areas: 37 (72.5 percent) and 26 (50.9 percent) cases, respectively. CONCLUSION: Ghrelin- and preproghrelin-immunoreactive cells are frequently present in endocrine hyperplasias associated with ABG. However, further studies are required to determine to what extent these hormones act as modulators of hyperplastic nodular growth and evolution.
INTRODUÇÃO: Grelina é um peptídeo de 28 aminoácidos secretado principalmente pelas células endócrinas da mucosa gástrica, acreditando-se que apresente ação moduladora relacionada com o crescimento celular. OBJETIVO: Estudar a presença de grelina e da molécula precursora preprogrelina na hiperplasia endócrina associada à gastrite atrófica do corpo (GAC). MATERIAL E MÉTODOS: Biópsias endoscópicas de 54 pacientes com GAC foram processadas para imuno-histoquímica, e anticorpos específicos contra grelina, preprogrelina e cromogranina foram utilizados. As células imunorreativas foram examinadas na hiperplasia endócrina presente na mucosa atrófica e nas áreas de metaplasia intestinal e pseudoantral. RESULTADOS: Ocorreu expressão de grelina em número variável de células endócrinas hiperplásicas em todos os pacientes estudados. Diferença estatisticamente significativa foi encontrada entre a frequência de nódulos hiperplásicos com mais de 50 por cento de células imunomarcadas por cromogranina e grelina ou por cromogranina e preprogrelina. O número médio de nódulos hiperplásicos por paciente demonstrado pela cromogranina foi de 8,6. A maioria desses nódulos apresentou células imunorreativas para grelina e preprogrelina, respectivamente, 5,1 e 5,6, em média. A presença da expressão imuno-histoquímica de grelina e preprogrelina foi incomum em glândulas exibindo metaplasia intestinal, respectivamente, em quatro (9,5 por cento) e nove (21,4 por cento) casos e foram frequentes nas áreas de metaplasia pseudoantral em, respectivamente, 37 (72,5 por cento) e 26 (50,9 por cento) casos. CONCLUSÃO: Células imunorreativas a grelina e preprogrelina estão presentes na hiperplasia endócrina associada à GAC. Entretanto, mais estudos são necessários para saber até que ponto esses hormônios estão atuando como moduladores do crescimento e a evolução desses nódulos hiperplásicos.
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Humanos , Células Endócrinas/patologia , Gastrite Atrófica , Grelina , Hiperplasia , Imuno-HistoquímicaRESUMO
INTRODUCTION: Ghrelin is a 28 amino acid peptide secreted mainly by endocrine cells present in the gastric mucosa and acknowledged as an endogenous releaser of growth hormone. The immunohistochemical expression of ghrelin has been described in neuroendocrine tumors, and it is believed that may exert modulating action related to the growth of these tumors. OBJECTIVE: To study the presence of ghrelin and preproghrelin immunoreactive cells in gastric neuroendocrine tumors associated with atrophic body gastritis. METHODS: Endoscopic biopsies from 15 patients with neuroendocrine tumor of the gastric mucosa associated with atrophic body gastritis were performed for immunohistochemistry, and specific chromogranin, ghrelin and preproghrelin antibodies were applied. The immunohistochemical expression was assessed in tumor cells and endocrine micronodular hyperplasia present in mucosa adjacent to the tumor, and it was classified in relation to the number of stained cells. RESULTS: Chromogranin was positive in 14 out of 15 tumors. Ghrelin and preproghrelin immunoreactive cells were detected in 11 (73 percent) and 13 (87 percent) tumors, respectively. There was a significant correlation between the immunohistochemical results of both antigen expressions (kappa = 81 percent). Ghrelin and preproghrelin expression was detected in hyperplastic nodules present in the mucosa adjacent to the tumor in seven and eight cases, respectively. There was no correlation between these results and those observed in neoplastic cells. CONCLUSION: Ghrelin and preproghrelin immunoreactive cells may be found in variable number in Type I neuroendocrine gastric tumors and in hyperplastic nodules associated with these tumors. However, it remains unclear what role these peptides play on the development of these tumors.
INTRODUÇÃO: Grelina é um peptídeo de 28 aminoácidos, reconhecido como liberador endógeno do hormônio do crescimento, sendo secretado principalmente por células endócrinas da mucosa gástrica. A expressão imuno-histoquímica da grelina tem sido descrita em tumores neuroendócrinos, acreditando-se que possa ter ação moduladora relacionada com o crescimento desses tumores. OBJETIVO: Estudar a presença de células imunorreativas a grelina e pré-progrelina em tumores neuroendócrinos gástricos associados à gastrite crônica atrófica do corpo. MÉTODOS: Biópsias endoscópicas de 15 pacientes portadores de tumor neuroendócrino da mucosa gástrica, associados à gastrite crônica atrófica do corpo, foram obtidas para as colorações imuno-histoquímicas, utilizando-se anticorpos contra cromogranina, grelina e pré-progrelina. A expressão imuno-histoquímica foi avaliada nas células tumorais e na hiperplasia endócrina micronodular presente na mucosa adjacente ao tumor e classificada em relação ao número de células coradas. RESULTADOS: A cromogranina foi positiva em 14 dos 15 tumores. Células imunorreativas à grelina foram detectadas em 11 (73 por cento) tumores e à pré-progrelina em 13 (87 por cento), ocorrendo excelente concordância (kappa = 81 por cento) entre os resultados imuno-histoquímicos dos dois antígenos. A expressão de grelina e pré-progrelina foi detectada em nódulos hiperplásicos presentes na mucosa adjacente ao tumor em sete e oito casos, respectivamente, não ocorrendo concordância entre esses resultados e aqueles observados nas células neoplásicas. CONCLUSÃO: Células imunorreativas a pré-progrelina e grelina podem ser encontradas em número variável nos tumores neuroendócrinos tipo I do estômago e nas lesões hiperplásicas associadas a esses tumores. Entretanto, permanece obscuro o papel desses peptídeos em relação ao desenvolvimento desses tumores.
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Humanos , Gastrite Atrófica , Grelina , Hiperplasia , Tumores Neuroendócrinos , Neoplasias GástricasRESUMO
Objective:To investigate the relationships between Leu72Met polymorphism ofpreproghrelin gene and type 2 diabetes mellitus (T2DM)in Han ethnics ofGuangzhou.Methods:We conducted a case-control study using 95 non-T2DM healthy individuals as controls (the control group)and 102 individuals diagnosed with T2DM as patients(the T2DM group)from populations of Han ethnics in Guangzhou,in order to detect genotypes of Leu72Met polymorphism of preproghrelin gene within each group,and to compare the differ-ences of genotypic and allelic frequencies between the two groups.Various molecular biology techniques were employed in the study in-cluding target gene segments amplification using the polymerase chain reaction(PCR).After amplification,digestions of PCR products were carried out using restriction enzyme BseNⅠand fragments obtained were detected using Native-PAGE in conjunction with a highly sensitive silver stain method.Results:In the healthy control group,the genotypes CC and AC were detected in 68 and 27 individuals,re-spectively,while no genotype AA was detected in this group.Their corresponding genotypic frequencies were 0.716,0.284,and 0,re-spectively.In the T2DM group,the genotypes CC,AC,and AA were detected in 71,25,and 6 cases,respectively.Their corresponding genotypic frequencies were 0.696,0.245,and 0.059,respectively.Allele frequencies detected were in equilibrium with the Hardy-Wein-berg equation.However,there were no significant differences between the control group and the T2DM group in terms of genotypic and al-lelic frequencies.Conclusion:There are no significant relationships between Leu72Met polymorphism of preproghrelin gene and T2DM in Han ethnics of Guangzhou.However,genotype AA was detected in the T2DM group but not in control,which suggested that allele A may play certain roles in T2DM development.Further investigations certainly would be worth pursuing.
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0.05). Conclusion Preproghrelin-Leu72Met is not significantly associated with T2DM and DN in Shanghai Han populations,while T2DM with AA genotype is characterized by significant declination in urine microalbumin when compared with CA and CC genotypes.Leu72Met polymorphism(C→A)may postpone the development of microalbuminuria in T2DM subjects.
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Background:Ghrelin is a new endogenous ligand for the growth hormone secretagogue receptor. It activates the release of growth hormone from the pituitary and it also participates in the regualtion of energy homeostasis. The aims of the study were to characterize the changes in plasma ghrelin levels in obese subjects compared with lean control or overweight subjects, and their relationship to various parameters in obese subjects. METHODS:In this study, 121 elementary school children were divided into 3 groups according to their body mass index (BMI). The lean control subjects consisted of 28 children who had less than 85 percentile of BMI. The overweight subjects consisted of 22 children who had 85-95 percentile of BMI. The obese subjects consisted of 71 children who had over 95 percentile of BMI. All subjects in 3 groups were evaluated according to their age, height, weight, obesity index, plasma ghrelin, serum lipid, glucose and insulin levels. Leu72Met mutation of prepro-ghrelin gene was directly detected by digesting the PCR fragments with Bsrl. RESULTS:Among antropometric data, body weight, BMI and obesity index were higher in obesity and overweight subjects than those of lean control subjects (P<0.05). The plasma ghrelin levels were significantly lower in overweight and obese subjects (P<0.05). In addition, serum triglyceride and LDL cholesterol levels were significantly higher in these groups compared to the control subjects (P<0.05). The concentrations of plasma ghrelin were significantly negatively correlated with BMI, obesity index, serum triglyceride, LDL cholesterol and insulin in all the children. However, there was no significant relationship between plasma ghrelin levels and any various parameters in obese subjects. Leu72Met mutation was detected in about 30% of obese children. However, we could not find any differences between lean control and obese children. CONCLUSION: We proved a significantly lower plasma ghrelin levels in overweight and obese subjects. Further studies are now needed to establish the role of ghrelin in the pathogenesis of human obesity.