Institute Pesquisas Biomedicas IPB

Brazil

Institute Pesquisas Biomedicas IPB

Brazil
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Czepielewski R.S.,Institute Pesquisas Biomedicas IPB | Jaeger N.,Institute Pesquisas Biomedicas IPB | Marques P.E.,Federal University of Minas Gerais | Antunes M.M.,University Federal Of Minas Geraismg | And 10 more authors.
European Journal of Immunology | Year: 2017

Drug-induced liver injury (DILI) is a major cause of acute liver failure (ALF), where hepatocyte necrotic products trigger liver inflammation, release of CXC chemokine receptor 2 (CXCR2) ligands (IL-8) and other neutrophil chemotactic molecules. Liver infiltration by neutrophils is a major cause of the life-threatening tissue damage that ensues. A GRPR (gastrin-releasing peptide receptor) antagonist impairs IL-8-induced neutrophil chemotaxis in vitro. We investigated its potential to reduce acetaminophen-induced ALF, neutrophil migration, and mechanisms underlying this phenomenon. We found that acetaminophen-overdosed mice treated with GRPR antagonist had reduced DILI and neutrophil infiltration in the liver. Intravital imaging and cell tracking analysis revealed reduced neutrophil mobility within the liver. Surprisingly, GRPR antagonist inhibited CXCL2-induced migration in vivo, decreasing neutrophil activation through CD11b and CD62L modulation. Additionally, this compound decreased CXCL8-driven neutrophil chemotaxis in vitro independently of CXCR2 internalization, induced activation of MAPKs (p38 and ERK1/2) and downregulation of neutrophil adhesion molecules CD11b and CD66b. In silico analysis revealed direct binding of GRPR antagonist and CXCL8 to the same binding spot in CXCR2. These findings indicate a new potential use for GRPR antagonist for treatment of DILI through a mechanism involving adhesion molecule modulation and possible direct binding to CXCR2. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim


Tractenberg S.G.,Grande Rio University | Viola T.W.,Grande Rio University | Rosa C.S.O.,Grande Rio University | Donati J.M.,Grande Rio University | And 4 more authors.
Jornal Brasileiro de Psiquiatria | Year: 2012

Objective: To determine the occurrence of trauma and posttraumatic stress disorder (PTSD) in a sample of women addicted to crack cocaine type. Method: The sample comprised 99 women, between 18 and 52 years admitted to a detoxification unit and extensively assessed by SCID-I and ASI-6. Results: There was a trauma exposure rate of 86.9% among women addicted to crack cocaine type. The rate of PTSD in the sample was 15.1%. The clusters of experiencing and hyper arousal were the most frequent, 24.4% and 20.9% respectively. Among the types of events reported most frequently were suffering assault/physical abuse and witnessing violence to others. Conclusion: The results suggest a frequent exposure to traumatic events. With regard to age of the traumatic experience, it is suggested that users exposed to trauma during childhood and adolescence showed a beginning drug use at earlier ages than those whose trauma occurred in adulthood.

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