Filamin A and DRD2 expression in corticotrophinomas.

PURPOSE: Filamin A (FLNA) expression is related to dopamine receptor type 2 (DRD2) expression in prolactinomas. Nevertheless, in corticotrophinomas, there are few studies about DRD2 expression and no data on FLNA. Therefore, we evaluated FLNA and DRD2 expression in corticotrophinomas and their association with tumor characteristics. METHODS: DRD2 and FLNA expression by immunohistochemistry, using H-score, based on the percentage of positive cells in a continuous scale of 0-300, were evaluated in 23 corticotrophinomas samples from patients submitted to neurosurgery. In six patients, treatment with cabergoline was indicated after non curative surgery. RESULTS: Twenty-two patients were female and one male. Regarding tumor size, 10 were micro and 12 were macroadenomas. DRD2 expression was found in 89% of cases and did not correlate with FLNA expression. Moreover, the response to cabergoline, observed in 33% of the cases, did not correlate with DRD2 nor FLNA expression. FLNA expression was not associated with clinical and tumor characteristics, except for sphenoid sinus invasion. CONCLUSIONS: In our cohort of corticotrophinomas, DRD2 expression was not associated with FLNA expression nor to the response to CAB. Nonetheless, FLNA expression could be related to tumor invasiveness.

Complement C5 controls liver lipid profile, promotes liver homeostasis and inflammation in C57BL/6 genetic background.

Innate immunity contributes effectively to the development of alcoholic liver disease (ALD). In special, the activation of the complement system is involved in the pathogenesis of this disease. Here we investigated the contribution of complement C5 protein to the establishment and maintenance of ALD. Eight- to ten-week-old B6C5(+) and B6C5(-) male mice were fed with high fat diet (HFD) only or the same diet containing equicaloric supplements of ethanol (HFDE) or maltodextrin (HFDM) for 10 weeks. Serum parameters of liver function as alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (AP), albumin, glucose, triglycerides (TG) and cholesterol were evaluated. Liver tissue samples were collected for histopathological analysis, lipid extraction (TG and cholesterol), cytokines (TNF-α, IL-6, IL-1ß, IL-10, IL-12, IL-17, IFN-γ, TGF-ß) measurement and NO production. We observed that B6C5(-) mice HFDE-fed accumulated more liver cholesterol and TG, increased liver IL-17 and IL-10 levels and reduced liver TGF-ß levels when compared to HFD-fed mice. We also observed that serum AST, AP and albumin were increased in B6C5(-) mice. Liver IL-1ß, IL-6, IL-12 and IFN-γ were decreased in B6C5(-) mice independently of diet. We conclude that C5 acts in the control of serum TG and cholesterol, liver cholesterol deposition, liver homeostasis and C5 promotes a pro-inflammatory liver environment in our mouse model of ALD.

The complement component C5 promotes liver steatosis and inflammation in murine non-alcoholic liver disease model.

Non-Alcoholic Fatty Liver Disease (NALD) is considering a hepatic manifestation of metabolic syndrome. Although the pathogenesis of NALD is not completely understood, insulin resistance and inflammatory cytokines are implicated. Considering that component C5 is a central mediator of inflammation, we investigated the role of C5 in the establishment of NALD. Eight to ten-week old B6 C5(+) and A/J C5(-) male mice were fed a high fat diet containing glucose (HFDG) for 6 and 10 weeks. We observed that B6 C5(+) mice HFDG-fed for 10 weeks developed hepatomegaly, triglycerides (TG) accumulation, steatosis and enhanced liver TNF-α, IL-6, IL-12p70 and IL-17 levels when compared to A/J C5(-) mice. Next, B6 C5(+) mice were compared with congenic B6 C5(-) mice. Again, B6 C5(+) HFDG-fed mice developed more steatosis, liver centro-lobular inflammation and presented higher levels of liver IL-1ß, IL-12p70, IL-17 and TFG-ß than B6 C5(-) mice under the same conditions. B6 C5(+) mice HFDG-fed also presented lower concentrations of serum albumin, serum cholesterol, blood leukocytes and liver NO production when compared with B6 C5(-) mice. We concluded that murine C5 contributes effectively to liver steatosis and inflammation in NALD pathogenesis. In addition, C5 is also important to control serum cholesterol and albumin levels in the C57BL/6 genetic background.

Effects of short term fasting on the evolution of fecal peritonitis in mice.

PURPOSE: To investigate the effect of 72 hours food suppression on the evolution of fecal peritonitis in mice evaluating the mortality and measuring the number and size of abscesses formed into the peritoneal cavity. METHODS: Mice receiving commercial diet and water ad libitum (control group, N=35) and mice fasted during 72 h (N=35), receiving only water ad libitum, were inoculated by i.p. route, with 4uL/g body weight of a fecal suspension diluted 1:6 or 1:9 in 0.15M NaCl solution (1:6 dilution, 22 controls and 18 fasted; 1:9 dilution, 13 controls and 17 fasted). Animals were followed up until two weeks after fecal inoculation, when the survivors were euthanized for evaluation of the number and size of intra-peritoneal abscesses. Mortality was evaluated by Kaplan Meyer curves. RESULTS: Mortality was significantly higher in fasted groups than in controls. However the number and size of abscesses were significantly less in fasted groups than in controls. CONCLUSION: Seventy two hours food suppression increased the susceptibility to endotoxic shock (high mortality after peritonitis induction) and the resistance to infection with fecal microorganisms (less number and size of intra-peritoneal abscesses).

Efeitos de jejum de curta duração na evolução de peritonite fecal em camundongos / Effects of short term fasting on the evolution of fecal peritonitis in mice

PURPOSE: To investigate the effect of 72 hours food suppression on the evolution of fecal peritonitis in mice evaluating the mortality and measuring the number and size of abscesses formed into the peritoneal cavity. METHODS: Mice receiving commercial diet and water ad libitum (control group, N=35) and mice fasted during 72 h (N=35), receiving only water ad libitum, were inoculated by i.p. route, with 4uL/g body weight of a fecal suspension diluted 1:6 or 1:9 in 0.15M NaCl solution (1:6 dilution, 22 controls and 18 fasted; 1:9 dilution, 13 controls and 17 fasted). Animals were followed up until two weeks after fecal inoculation, when the survivors were euthanized for evaluation of the number and size of intra-peritoneal abscesses. Mortality was evaluated by Kaplan Meyer curves. RESULTS: Mortality was significantly higher in fasted groups than in controls. However the number and size of abscesses were significantly less in fasted groups than in controls. CONCLUSION: Seventy two hours food suppression increased the susceptibility to endotoxic shock (high mortality after peritonitis induction) and the resistance to infection with fecal microorganisms (less number and size of intra-peritoneal abscesses).

OBJETIVO: Investigar o efeito de jejum de 72 horas na evolução de peritonite fecal em camundongos, avaliando a mortalidade e o número e tamanho dos abscessos formados na cavidade peritoneal. MÉTODOS: Camundongos recebendo dieta ad libitum (grupo controle, N=35) e camundongos submetidos a jejum durante 72h (N=35) foram inoculados, por via intraperitoenal, com 4uL/g de peso corporal de uma suspensão de fezes diluída a 1:6 ou 1:9 em NaCl 15M (diluição 1:6, 22 controles e 18 jejum; diluição 1:9, 13 controles e 17 jejum). Os animais foram acompanhados até duas semanas após a inoculação das fezes quando eram eutanaziados para avaliação do número e tamanho dos abscessos intraperitoneais. A mortalidade foi avaliada através das curvas de Kaplan Meyer. RESULTADOS: A mortalidade foi significativamente maior nos animais submetidos ao jejum. No entanto o número e tamanho dos abscessos foram significativamente menores neste grupo. CONCLUSÃO: O jejum de 72 horas aumentou a susceptibilidade ao choque endotóxico (maior mortalidade nas primeiras 48 horas) e aumento da resistência aos microorganismos fecais (menor número e tamanho dos abscessos intraperitoneais).