Differential expression of genes encoding proteins of the HGF/MET system in insulinomas

Abstract\ud \ud Background\ud Insulinomas are the most common functional pancreatic neuroendocrine tumors, whereas histopathological features do not predict their biological behaviour. In an attempt to better understand the molecular processes involved in the tumorigenesis of islet beta cells, the present study evaluated the expression of genes belonging to the hepatocyte growth factor and its receptor (HGF/MET) system, namely, MET, HGF; HGFAC and ST14 (encode HGF activator and matriptase, respectively, two serine proteases that catalyze conversion of pro-HGF to active HGF); and SPINT1 and SPINT2 (encode serine peptidase inhibitors Kunitz type 1 and type 2, respectively, two inhibitors of HGF activator and of matriptase).\ud \ud \ud Methods\ud Quantitative real-time reverse transcriptase polymerase chain reaction was employed to assess RNA expression of the target genes in 24 sporadic insulinomas: 15 grade 1 (G1), six grade 2 (G2) and three hepatic metastases. Somatic mutations of MET gene were searched by direct sequencing of exons 2, 10, 14, 16, 17 and 19.\ud \ud \ud Results\ud Overexpression of MET was observed in the three hepatic metastases concomitantly with upregulation of the genes encoding HGF and matriptase and downregulation of SPINT1. A positive correlation was observed between MET RNA expression and Ki-67 proliferation index while a negative correlation was detected between SPINT1 expression and the mitotic index. No somatic mutations were found in MET gene.\ud \ud \ud Conclusion\ud The final effect of the increased expression of HGF, its activator (matriptase) and its specific receptor (MET) together with a decreased expression of one potent inhibitor of matriptase (SPINT1) is probably a contribution to tumoral progression and metastatization in insulinomas

Gut microbiota characterization in women with obesity, normal weight, constitutional thinness, and anorexia nervosa

INTRODUÇÃO: Obesidade (OB) e anorexia nervosa (AN) são doenças crônicas de etiologia multifatorial, de difícil tratamento e associadas com aumento do risco de mortalidade em relação à população geral. A identificação de fatores que influenciam essas doenças pode levar à melhor compreensão dos mecanismos fisiopatológicos envolvidos e à descoberta de novos alvos terapêuticos. A magreza constitucional (MC) é caracterizada por baixo peso na ausência de desnutrição, excesso de exercícios ou doenças crônicas que impliquem em perda ponderal, e pela presença de menstruações regulares e resistência natural e fisiológica ao ganho de peso. Estudos revelaram diferenças entre a microbiota intestinal (MI) de pessoas com OB e com peso normal (PN), e mais recentemente, entre indivíduos com AN e com PN. OBJETIVO: Caracterizar e comparar parâmetros antropométricos, metabólicos, de saúde mental e a MI de mulheres com OB, PN, AN e MC. MÉTODOS: Essa tese foi composta pela compilação de dois artigos. No primeiro, avaliamos e comparamos aspectos de saúde mental avaliados por questionários nos quatro grupos, correlacionando- os às variáveis antropométricas e laboratoriais. No segundo, caracterizamos e comparamos a MI (a partir da extração e sequenciamento do DNA bacteriano presente nas amostras fecais), avaliando também as correlações dos resultados da MI com os parâmetros antropométricos, laboratoriais e de saúde mental. Foram avaliadas 77 mulheres de 18 a 40 anos (20 com OB, 19 com PN, 20 com MC e 20 com AN). RESULTADOS: As mulheres com AN apresentaram os maiores escores em ansiedade e checagem corporal (p0,3 e p 0.3 e p <0,05 for all). Differences in GM among the four groups emerged at every taxonomic level. OB showed a significant increase of the phylum Proteobacteria when compared to AN and CT, and of the genera Butyricimonas than other groups. On the contrary, genera Roseburia were depleted in AN in comparison to CT and NW, as well as the species Anaerotruncus colihominis, in comparison to NW. Akkermansia muciniphila was more prevalent in NW group than in CT (p<0.05 for all). Associations among bacterial community structure, body fat parameters, metabolic markers, and questionnaires scores were also identified (p<0.05). CONCLUSION: Although women with AN and CT may resemble physically, they have important mental health differences. Women with OB and AN presented higher mental health impairment (depression, eating misbehavior and body shape dissatisfaction) than women with NW and CT. GM differences were observed among the four groups in all taxonomic levels, and correlations between bacterial species and anthropometric, laboratorial, and mental health parameters suggest some GM influence in OB and AN physiopathology. More studies are necessary to prove any causality effec

Doppler velocimetry and fetal well-being assessment exams performance’s study for adverse neonatal outcomes

Este estudo retrospectivo e transversal teve como objetivo verificar o desempenho dos exames antenatais, para a predição de resultados pós-natais adversos. Selecionaram-se 1.387 pacientes com alto risco gestacional, no Setor de Avaliação da Vitalidade Fetal, da Clínica Obstétrica do Hospital das Clínicas da FMUSP. O desempenho de todos os exames foi testado, para a predição dos resultados pós-natais adversos, por meio do cálculo da sensibilidade, especificidade, VPP e VPN. O enfoque inédito do estudo foi a divisão da amostra em dois subgrupos, estratificada segundo o risco imposto pelas doenças ou intercorrências obstétricas. O subgrupo de baixo risco composto por 659 casos, e o subgrupo de alto risco,por 728 casos. Os exames antenatais foram: Doppler umbilical, Doppler da artéria cerebralmédia, Doppler do ducto venoso, cardiotocografia e perfil biofísico fetal. Os resultados pós natais foram: prematuridade, desnutrição fetal, depressão neonatal (Apgar &lt; 7) e acidemia no nascimento. Todos os testes demonstraram melhores resultados no subgrupo de alto risco do que no subgrupo de baixo risco. Considerando-se a predição de todos os resultados neonatais adversos, o Doppler umbilical demonstrou melhores resultados.The aim of this retrospective study was to assess the role prenatal exams topredict neonatal adverse outcomes. The sample was divided according to maternal and gestational complications, as placental insufficiency ethiology. Furthermore, the predictive values of the exams were analyzed in relation to postnatal adverse outcomes. The sample was constituted by 1,387 high-risk pregnancies assisted in the Obstetrics Department - Fetal Well-being Assessment Section of the Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo - Brazil. The performance of all prenatal enrolled exams were evaluated in order to predict the adverse postnatal outcomes, using sensitivity, specificity,PPV and NPV estimations. The population approach was executed in two different subgroups,stratified according to the risk imposed by the obstetrical disease or complication. 659 casesand high-risk subgroup, 728 cases constituted the low-risk subgroup. The prenatal exams were: UA Doppler, middle cerebral artery Doppler, ductus venosus Doppler, cardiotocography and fetal biophysical profile. The postnatal results were: prematurity index, intrauterine growth restriction, neonatal asphyxia (Apgar &lt; 7) and acidemia at delivery. As far as the test performance is regarded, all of them demonstrated best results in the high-risk subgroup thanin the low-risk subgroup. In regarding to all postnatal abnormalities diagnosis, the UA Dopplerperformance was the best when compared with all other exams

Triple A Syndrome: Preliminary Response to the Antioxidant N-Acetylcysteine Treatment in a Child

Introduction: Triple A syndrome (AAAS) is a rare autosomal recessive disorder characterized by alacrima, achalasia, ACTH-resistant adrenal insufficiency, autonomic dysfunction, and progressive neurodegeneration. Increased oxidative stress, demonstrated in patients’ fibroblasts in vitro, may be a central disease mechanism. N-acetylcysteine protects renal function in patients with kidney injuries associated with increased oxidative stress and improves viability of AAAS-knockdown adrenal cells in vitro. Patient and Results: A boy diagnosed with AAAS presented with short stature and increased oxidative stress in vivo assessed by increased thiobarbituric acid reactive substances (TBARS), which are markers of lipid peroxidation, and by the susceptibility of LDL to oxidation and the capacity of HDL to prevent it. A homozygous missense germline mutation (c.523G>T, p.Val175Phe) in AAAS was identified. N-acetylcysteine (600 mg orally, twice daily) decreased oxidative stress but did not change the patient’s growth pattern. Conclusions: An increase in oxidative stress is reported for the first time in vivo in an AAAS patient. N-acetylcysteine was capable of decreasing TBARS levels, reducing the susceptibility of LDL to oxidation and improving the antioxidant role of HDL. The longterm effect of antioxidant treatment should be evaluated to determine the real benefit for the prevention of the degenerative process in AAAS