ABSTRACT
Abstract Objective: To evaluate the safety, tolerability and potential therapeutic effects of gastrin-releasing peptide in three children with autistic spectrum disorder. Methods: Case series study with the intravenous administration of gastrin-releasing peptide in the dose of 160 pmol/kg for four consecutive days. To evaluate the results, parental impressions the Childhood Autism Rating Scale (CARS) and the Clinical Global Impression (CGI) Scale. Each child underwent a new peptide cycle after two weeks. The children were followed for four weeks after the end of the infusions. Results: The gastrin-releasing peptide was well tolerated and no child had adverse effects. Two children had improved social interaction, with a slight improvement in joint attention and the interaction initiatives. Two showed reduction of stereotypes and improvement in verbal language. One child lost his compulsion to bathe, an effect that lasted two weeks after each infusion cycle. Average reduction in CARS score was 2.8 points. CGI was "minimally better" in two children and "much better" in one. Conclusions: This study suggests that the gastrin-releasing peptide is safe and may be effective in improving key symptoms of autism spectrum disorder, but its results should be interpreted with caution. Controlled clinical trials-randomized, double-blinded, and with more children-are needed to better evaluate the possible therapeutic effects of gastrin-releasing peptide in autism.
Resumo Objetivo: Avaliar a segurança, a tolerabilidade e os possíveis efeitos terapêuticos do peptídeo liberador de gastrina em três crianças com transtorno do espectro autista. Métodos: Estudo de casuística com administração intravenosa de peptídeo liberador de gastrina na dose de 160 pmol/kg por quatro dias consecutivos. Para avaliar os resultados, foram usadas a impressão dos pais, a Escala de Classificação de Autismo na Infância (CARS) e a Escala de Impressão Clínica Global (CGI). Cada criança foi submetida a novo ciclo de peptídeo após duas semanas. As crianças foram acompanhadas por quatro semanas após o término das infusões. Resultados: O peptídeo liberador de gastrina foi bem tolerado e nenhuma criança apresentou efeitos adversos. Duas crianças apresentaram melhoria na interação social, com melhoria na atenção compartilhada e nas iniciativas de interação. Duas mostraram redução dos estereótipos e melhoria na linguagem verbal. Uma criança perdeu sua compulsão por banhos, efeito que durou duas semanas após cada ciclo de infusão. A redução média no escore da CARS foi de 2,8 pontos. Quanto à CGI, os resultados foram "minimamente melhor em duas crianças" e "muito melhor" em uma. Conclusões: Este estudo sugere que o peptídeo liberador de gastrina é seguro e pode ser efetivo na melhoria dos principais sintomas do transtorno do espectro autista, porém seus resultados devem ser interpretados com cautela. Ensaios clínicos controlados, randomizados, duplo-cegos e com maior número de crianças são necessários para melhor avaliar os possíveis efeitos terapêuticos do peptídeo liberador de gastrina sobre o autismo.
Subject(s)
Humans , Male , Child, Preschool , Gastrin-Releasing Peptide/administration & dosage , Autism Spectrum Disorder/drug therapy , Treatment Outcome , Administration, Intravenous , Autism Spectrum Disorder/diagnosisABSTRACT
@#Objective To investigate the effect of postnatal music exposure on fearful behavior of prenatal stressed rats in defensive withdrawal test and the expression of gastrin-releasing peptide receptor (GRPR) in the amygdala. Methods Wistar pregnant rats were divided in stress group (n=8) and control group (n=8). The stress group were immobilized and bright lighted 45 min, 3 times a day, when gestation 11-20 days, while the control group without any stress. The new born rats from the stress group were exposed in music (SM group) or white noise (SW group) for 45 min twice a day since 1 day after born, and the rats from the control (SC) group left undisturbed. They were tested with defensive withdrawal test 60 days after birth, and the GRPR levels in the amygdala were measured with immunofluorescence and real-time PCR. Results The latency was shorter and the frequence out of the chamber was the most in the SM group of the defensive withdrawal test (P<0.001), while GRPR-positive cells and GRPR mRNA increased in amygdala (P<0.001). Conclusion Postnatal music exposure can counteract the abnormal behavior response of prenatal stressed offspring and accompany with increased expression of GRPR in the amygdala.
ABSTRACT
Objective To investigate the effect of postnatal music exposure on fearful behavior of prenatal stressed rats in defensive withdrawal test and the expression of gastrin-releasing peptide receptor (GRPR) in the amygdala. Methods Wistar pregnant rats were divid-ed in stress group (n=8) and control group (n=8). The stress group were immobilized and bright lighted 45 min, 3 times a day, when gesta-tion 11-20 days, while the control group without any stress. The new born rats from the stress group were exposed in music (SM group) or white noise (SW group) for 45 min twice a day since 1 day after born, and the rats from the control (SC) group left undisturbed. They were tested with defensive withdrawal test 60 days after birth, and the GRPR levels in the amygdala were measured with immunofluorescence and real-time PCR. Results The latency was shorter and the frequence out of the chamber was the most in the SM group of the defensive withdrawal test (P<0.001), while GRPR-positive cells and GRPR mRNA increased in amygdala (P<0.001). Conclusion Postnatal music ex-posure can counteract the abnormal behavior response of prenatal stressed offspring and accompany with increased expression of GRPR in the amygdala.
ABSTRACT
Objective To investigate the regulatory effects of bombesin on the growth of human immortalized gastric epithelial cell line(GES-1), and its mechanisms. Methods ① The expression of gastrin releasing peptide receptor(GRP-R) mRNA in GES-1 was detected. ② The expression of GRP-R protein was tested by cross-linking experiment and the location of the receptors in the cells were investigated by cytochemistry. ③GES-1 cell line was incubated with varying concentrations of bombesin with or without its antagonist and growth of the cell line was determined. ④The effect of protein kinase C (PKC) inhibitor on cell growth induced by bombesin was studied. ⑤After treated with bombesin, the intracellular IP 3 and translocation of PKC activity were measured in GES-1. ⑥Semiquantification of GRP-R mRNA in this cell line treated with bombesin was performed. Results ①Expression of mRNA of GRP-R was demonstrated in GES-1 cells. ②The GRP-R protein was about 75?103 as revealed by cross-linking study, and the receptors were identified on the cell membranes by cytochemistry. ③Bombesin stimulated the growth of GES-1 significantly, which could be inhibited by specific antagonist of bombesin. ④Bombesin-induced growth of GES-1 was also inhibited by PKC inhibitor. ⑤Bombesin induced an increase of IP 3 generation in GES-1 as well as remarkable translocation of PKC activity from cytoplasm to the cell membranes. ⑥An increase in GRP-R mRNA was induced by treatment of cell line with bombesin. Conclusions Bombesin stimulates the growth of this GES-1 via its receptor GRP-R and through IP 3, PKC signal pathway. The increase in expression of GRP-R mRNA in GES-1 induced by bombesin indicates that bombesin might upregulate the GRP-R in the GES-1 cells.