A Interleucina 1-beta mostra uma ação protetora na fase aguda do modelo de epilepsia induzido pela pilocarpina / The il1β have a protective action in the acute phase of the pilocarpine-induced epilepsy model

INTRODUÇÃO: Existem contradições na literatura quanto aos efeitos dos genes il1β e il1rn nas epilepsias. Nosso objetivo foi avaliar os efeitos do silenciamento desses dois genes na fase aguda do modelo de epilepsia induzido pela pilocarpina. MÉTODOS: Para alterar a expressão dos genes il1β e il1rn utilizamos a técnica de interferência por RNA. RESULTADOS: Obtivemos taxas de silenciamento significativas para os dois genes no sistema nervoso central. Observamos efeitos fenotípicos significativos, incluindo a alteração na taxa de mortalidade dos animais 5 dias após a indução do modelo. CONCLUSÕES: A il1β parece exercer um papel protetor na fase aguda do modelo de epilepsia induzido pela pilocarpina.

INTRODUCTION: There is contradictory information regarding the of effects il1β and il1rn in epilepsy. We aimed to evaluate the effect of silencing both genes in the acute phase of the pilocarpine-induced epilepsy model. METHODS: We used RNA interference in order to achieve gene silencing. RESULTS: We obtained significant gene silencing in the central nervous system. In addition, we observed phenotypic effects including differences in mortality rates of animals 5 days after pilocarpine injections. CONCLUSION: Our results indicate that il1β seems to have a protective effect in the acute phase of the pilocarpine-induced epilepsy model.

Inflammatory response in a rat model of gastroschisis is associated with an increase of NF-kappaB

Babies with gastroschisis have high morbidity, which is associated with inflammatory bowel injury caused by exposure to amniotic fluid. The objective of this study was to identify components of the inflammatory response in the intestine and liver in an experimental model of gastroschisis in rats. The model was surgically created at 18.5 days of gestation. The fetuses were exposed through a hysterotomy and an incision at the right of the umbilicus was made, exposing the fetal bowel. Then, the fetus was placed back into the uterus until term. The bowel in this model had macro- and microscopic characteristics similar to those observed in gastroschisis. The study was conducted on three groups of 20 fetuses each: gastroschisis, control, and sham fetuses. Fetal body, intestine and liver weights and intestine length were measured. IL-1â, IL-6, IL-10, TNF-á, IFN-ã and NF-kappaB levels were assessed by ELISA. Data were analyzed statistically by ANOVA followed by the Tukey post-test. Gastroschisis fetuses had a decreased intestine length (means ± SD, 125 ± 25 vs 216 ± 13.9; P < 0.005) and increased intestine weight (0.29 ± 0.05 vs 0.24 ± 0.04; P < 0.005). Intestine length correlated with liver weight only in gastroschisis fetuses (Pearson’s correlation coefficient, r = 0.518, P = 0.019). There were no significant differences in the concentrations of IL-1â, TNF-á or IFN-ã in the intestine, whereas the concentration of NF-kappaB was increased in both the intestine and liver of fetuses with gastroschisis. These results show that the inflammatory response in the liver and intestine of the rat model of gastroschisis is accompanied by an increase in the amount of NF-kappaB in the intestine and liver.

Non-obese adult onset diabetes with oral hypoglycemic agent failure: islet cell autoantibodies or reversible beta cell refractoriness?

Pancreatic ß cell function and insulin sensitivity, analyzed by the homeostasis model assessment, before and after 24 weeks of insulin therapy were studied and correlated with the presence of autoantibodies against ß cells (islet cell and anti-glutamic acid decarboxylase antibodies), in a group of 18 Brazilian lean adult non-insulin-dependent diabetes mellitus (NIDDM) patients with oral hypoglycemic agent failure (OHAF). Median fasting plasma glucose before and after insulin treatment was 19.1 and 8.5 mmol/l, respectively (P < 0.001); median HbA1c was 11.7 percent before vs 7.2 percent after insulin treatment (P < 0.001). Forty-four percent of the patients were positive (Ab+) to at least one autoantibody. Fasting C-peptide levels were lower in Ab+ than Ab- patients, both before (Ab+: 0.16 ± 0.09 vs Ab-: 0.41 ± 0.35 nmol/l, P < 0.003) and after insulin treatment (Ab+: 0.22 ± 0.13 vs Ab-: 0.44 ± 0.24 nmol/l, P < 0.03). Improvement of Hß was seen in Ab- (median before: 7.3 vs after insulin therapy: 33.4 percent, P = 0.003) but not in Ab+ patients (median before: 6.6 vs after insulin therapy: 20.9 percent). These results show that the OHAF observed in the 18 NIDDM patients studied was due mainly to two major causes: autoantibodies and ß cell desensitization. Autoantibodies against ß cells could account for 44 percent of OHAF, but Ab- patients may still present ß cell function recovery, mainly after a period of ß cell rest with insulin therapy. However, the effects of ß cell function recovery on the restoration of the response to oral hypoglycemic agents need to be determined

Insulin receptor has tyrosine kinase activity toward Shc in rat liver

Insulin induces tyrosine phosphorylation of Shc in cell cultures and in insulin-sensitive tissues of the intact rat. However, the ability of insulin receptor (IR) tyrosine kinase to phosphorylate Shc has not been previously demonstrated. In the present study, we investigated insulin-induced IR tyrosine kinase activity towards Shc. Insulin receptor was immunoprecipitated from liver extracts, before and after a very low dose of insulin into the portal vein, and incubated with immunopurified Shc from liver of untreated rats. The kinase assay was performed in vitro in the presence of exogenous ATP and the phosphorylation level was quantified by immunoblotting with antiphosphotyrosine antibody. The results demonstrate that Shc interacted with insulin receptor after infusion of insulin, and, more important, there was insulin receptor kinase activity towards immunopurified Shc. The description of this pathway in animal tissue may have an important role in insulin receptor tyrosine kinase activity toward mitogenic transduction pathways.

Avaliaçäo dos protozoários ciliados no rúmen de búfalos (Bubalus bubalis L) e bovinos (Bos indicus L) em regime de confinamento / Rumen ciliate protozoa in buffalo (Bubalus bubalis, L) and zebu cattle (Bos indicus, L) kept in a feedlot

Num experimento de engorda em confinamento, foram utilizado nove bubalinos e nove zebuínos, todos machos castrados, de 18 a 24 meses de idade e peso médio de 340 kg, mantidos em baias individuais, consumindo dieta de 2,0 kg de soja crua moída, 2,0 kg de espigas de milho desintegradas (gräo, palha e sabugo) e silagem de sorgo à vontade (controlando-se o consumo diário). Ao final do período de confinamento, todos os animais foram abatidos e o conteúdo ruminal de cada indivíduo foi homogeneizado, sendo colhidas amostras de 30 a 40 ml de líquido ruminal e, desta, retirou-se alíquota de 10 ml em tubo de ensaio com 20 ml de formaldeído diluído em água destilada a 1:2, para fixaçäo dos protozoários ciliados. As contagens de protozoários foram feitas em 100 campos e os resultados permitiram as seguintes conclusöes: 1) a dieta favoreceu maior concentraçäo de protozoários ciliados/ml de líquido ruminal dos zebuínos que no de bubalinos, apesar destes apresentarem maior número de gêneros; 2) os protozoários ciliados digestores de fibra foram detectados em maior quantidade nos zebuínos que nos bubalinos; 3) o gênero Entodinium spp representou mais de 80 por cento do total dos protozoários ciliados identificados nos zebuínos e nos bubalinos