Diacerhein attenuates the inflammatory response and improves survival in a model of severe sepsis

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Prolactin-signal transduction in neonatal rat pancreatic islets and interaction with the insulin-signaling pathway

FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOCAPES - COORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL E NÍVEL SUPERIORCNPQ – CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICODuring pregnancy, pancreatic islets undergo structural and functional changes in response to an increased demand for insulin. Different hormones, especially placental lactogens, mediate these adaptive changes. Prolactin (PRL) mainly exerts its biological effects by activation of the JAK2/STAT5 pathway. PRL also stimulates some biological effects via activation of IRS-1, IRS-2, PI 3-kinase, and MAPK in different cell lines. Since IRS-2 is important for the maintenance of pancreatic islet cell mass, we investigated whether PRL affects insulin-signaling pathways in neonatal rat islets. PRL significantly potentiated glucose-induced insulin secretion in islets cultured for 7 days. This effect was blocked by the specific PI 3-kinase inhibitor wortmannin. To determine possible effects of PRL on insulin-signaling pathways, fresh islets were incubated with or without the hormone for 5 or 15 min. Immunoprecipitation and immunoblotting with specific antibodies showed that PRL induced a dose-dependent IRS-1 and IRS-2 phosphorylation compared to control islets. PRL-induced increase in IRS-1/-2 phosphorylation was accompanied by an increase in the association with and activation of PI 3-kinase. PRL-induced IRS-2 phosphorylation and its association with PI 3-kinase did not add to the effect of insulin. PRL also induced JAK2, SHC, ERK1 and ERK2 phosphorylation in neonatal islets, demonstrating that PRL can activate MAPK. These data indicate that PRL can stimulate the IRSs/PI 3-kinase and SHC/ERK pathways in islets from neonatal rats355282289FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOCAPES - COORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL E NÍVEL SUPERIORCNPQ – CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOFAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOCAPES - COORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL E NÍVEL SUPERIORCNPQ – CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOsem informaçãosem informaçãosem informaçã

Disruption Of Metabolic Pathways - Perspectives For The Treatment Of Cancer

Several growth-promoting signaling pathways have tight molecular connections with metabolic-related signal transduction systems. By controlling these pathways, cancer cells gain autonomy over energy-acquiring systems and, thus, expand their potential for proliferation. Here, we discuss the use of drug and antisense oligonucleotide approaches to inhibit metabolic pathways in cancer cells and their potential use in the therapeutics of cancer. © 2006 Bentham Science Publishers Ltd.617787Gough, N.R., Ray, L.B., Mapping cellular signaling (2002) Sci. STKE, pp. EG8Levchenko, A., Computational cell biology in the post-genomic era (2001) Mol. Biol. 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Tear Film And Ocular Surface Changes In Diabetes Mellitus [alterações Do Filme Lacrimal E Da Superfície Ocular No Diabetes Mellitus]

Diabetes mellitus and its clinical association with dry eye and ocular surface are becoming a frequent and sometimes complicate problem in Ophthalmology. Epidemiological data show that an increase in the number of patients with this association is expected following the trend to rise of the disease. The present work reviews the clinical and functional aspects of this problem. The observations indicate that metabolic, neuropathic and vascular tissue damages lead to an inflammatory process and functional degeneration. The physiopathological mechanism include hyperglycemia, advanced glycated end product accumulation, oxidative stress and inflammation mediated by NF-κB signaling pathways. 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Esophagogastric Junction Adenocarcinoma: Multivariate Analyses Of Surgical Morbi-mortality And Adjuvant Therapy.

In recent years the literature has recorded a progressive increase in the prevalence of adenocarcinoma of the esophagogastric junction. Several factors can interfere with the morbidity and mortality of surgical treatment. Non-randomized retrospective study of prognostic factors of operated patients by adenocarcinoma of esophagogastric junction, with or without post-operative chemotherapy and radiotherapy. Medical records were reviewed from patients treated at university hospital in the period of 1989 and 2009, to obtain data about pre and postoperative treatment. Cox's univariate and multivariate regression analysis of risk factors for prognostic of these patients were done with level of significance of 5 %. Were reviewed 103 patients distributed as: 1) 78 (75.7%) patients without adjuvant therapy, and 2) 25 (24.3%) with it. All patients underwent surgical resection with curative intent. Cox's multivariate regression analysis of all patients showed that: lymphnode invasion N2 had greater risk of death in 5.9 times; broncopneumonia, in 11.4 times; tumoral recurrence during clinical following greater in 3.8 times. Tumoral recurrence, lymphnode metastasis and broncopneumonia in the postoperative period were factors of bad prognosis and contributed significantly to increase morbimortality and decrease global survival.25422923

Infliximab restores glucose Homeostasis in an animal model of diet-induced obesity and diabetes

FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOCNPQ – CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOTNF-alpha plays an important role in obesity-linked insulin resistance and diabetes mellitus by activating at least two serine kinases capable of promoting negative regulation of key elements of the insulin signaling pathway. Pharmacological inhibition of TNF-alpha is currently in use for the treatment of rheumatoid and psoriatic arthritis, and some case reports have shown clinical improvement of diabetes in patients treated with the TNF-alpha blocking monoclonal antibody infliximab. The objective of this study was to evaluate the effect of infliximab on glucose homeostasis and insulin signal transduction in an animal model of diabetes. Diabetes was induced in Swiss mice by a fat-rich diet. Glucose and insulin homeostasis were evaluated by glucose and insulin tolerance tests and by the hyperinsulinemic-euglycemic clamp. Signal transduction was evaluated by immunoprecipitation and immunoblotting assays. Short-term treatment with infliximab rapidly reduced blood glucose and insulin levels and glucose and insulin areas under the curve during a glucose tolerance test. Furthermore, infliximab increased the glucose decay constant during an insulin tolerance test and promoted a significant increase in glucose infusion rate during a hyperinsulinemic-euglycemic clamp. In addition, the clinical outcomes were accompanied by improved insulin signal transduction in muscle, liver, and hypothalamus, as determined by the evaluation of insulin-induced insulin receptor, insulin receptor substrate-1, and receptor substrate-2 tyrosine phosphorylation and Akt and forkhead box protein O1 serine phosphorylation. Thus, pharmacological inhibition of TNF-alpha may be an attractive approach to treat severely insulin-resistant patients with type 2 diabetes mellituso TEXTO COMPLETO DESTE ARTIGO, ESTARÁ DISPONÍVEL À PARTIR DE AGOSTO DE 2015.1481259915997FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOCNPQ – CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOFAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOCNPQ – CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOsem informaçãosem informaçã