RESUMO
The aim of this study was to determine whether the lactones dehydroleucodine, xanthatin and 3-benzyloxymethyl-5H-furan-2-one, would be effective in an animal model of gastric ulcer induced by mast cell activation. Rats were divided into ten groups. Treatments were repeated for four days. The degree of gastric erosion was assessed with a scoring system and histological preparations. Gastric mast cell morphology was analyzed by histological procedures. Serum serotonin levels were determined as markers of mast cell activation. Statistical analyses were done using ANOVA and Tukey-Kramer test. We demonstrated that the repeated administration of compound 48/80 results in extensive mucosal lesions in the gastric mucosa and that such lesions occurred in association with mast cell degranulation and a significant increase of serum serotonin. We showed that these lesions were prevented by dehydroleucodine, xanthatin, and 3-benzyloxymethyl-5H-furan-2-one and that this effect was similar to that obtained with sodium cromoglycate. In conclusion, the results of the present study indicate that the optimal gastric cytoprotective dose of dehydroleucodine, xanthatin, and 3-benzyloxymethyl-5H-furan-2-one is efficacious in an animal model of gastric ulcer induced by mast cell activation. Our findings suggest that these lactones could be valuable tools for designing novel therapeutic agents for digestive disorders associated with inappropriate mast cell activation.
Assuntos
Proliferação de Células/efeitos dos fármacos , Mucosa Gástrica/efeitos dos fármacos , Mastocitose/tratamento farmacológico , Úlcera Gástrica/tratamento farmacológico , Animais , Modelos Animais de Doenças , Furanos/farmacologia , Mucosa Gástrica/patologia , Humanos , Lactonas/farmacologia , Mastocitose/metabolismo , Mastocitose/patologia , Ratos , Sesquiterpenos/farmacologia , Úlcera Gástrica/metabolismo , Úlcera Gástrica/patologia , p-Metoxi-N-metilfenetilamina/farmacologiaRESUMO
The Theory of Self- vs. Externally-Regulated Learning™ (SRL vs. ERL) proposed different types of relationships among levels of variables in Personal Self-Regulation (PSR) and Regulatory Teaching (RT) to predict the meta-cognitive, meta-motivational and -emotional variables of learning, and of Academic Achievement in Higher Education. The aim of this investigation was empirical in order to validate the model of the combined effect of low-medium-high levels in PSR and RT on the dependent variables. For the analysis of combinations, a selected sample of 544 undergraduate students from two Spanish universities was used. Data collection was obtained from validated instruments, in Spanish versions. Using an ex-post-facto design, different Univariate and Multivariate Analyses (3 × 1, 3 × 3, and 4 × 1) were conducted. Results provide evidence for a consistent effect of low-medium-high levels of PSR and of RT, thus giving significant partial confirmation of the proposed rational model. As predicted, (1) the levels of PSR and positively and significantly effected the levels of learning approaches, resilience, engagement, academic confidence, test anxiety, and procedural and attitudinal academic achievement; (2) the most favorable type of interaction was a high level of PSR with a high level RT process. The limitations and implications of these results in the design of effective teaching are analyzed, to improve university teaching-learning processes.
RESUMO
The aim of the present study was to determine whether dehydroleucodine, xanthatin and 3-benzyloxymethyl-5H-furan-2-one inhibit the activation of human leukemic LAD2 mast cells induced by compound 48/80 or the calcium ionophore A23187. LAD2 cells were preincubated in the presence of test drugs and then challenged with the secretagogues. This study provides the first evidence in favor of the view that dehydroleucodine and xanthatin inhibit the degranulation of LAD2 cells, thus acting as human mast cell stabilizers. These molecules could be effective in the treatment of human diseases associated with inappropriate mast cell activation.
Assuntos
Furanos/farmacologia , Lactonas/farmacologia , Mastócitos/metabolismo , Sesquiterpenos/farmacologia , Calcimicina/farmacologia , Ionóforos de Cálcio/farmacologia , Degranulação Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Humanos , Cinética , Leucemia de Mastócitos/metabolismo , Leucemia de Mastócitos/patologia , Mastócitos/fisiologia , Mastócitos/ultraestrutura , Microscopia Eletrônica de Varredura , Microscopia Eletrônica de Transmissão , beta-N-Acetil-Hexosaminidases/metabolismo , p-Metoxi-N-metilfenetilamina/farmacologiaRESUMO
The present study was designed to examine the effects of a sesquiterpene lactone isolated from Artemisia douglasiana Besser (dehydroleucodine), a xanthanolide sesquiterpene isolated from Xanthium cavanillesii Schouw (xanthatin) and a semisynthetic butenolide (3-benzyloxymethyl-5H-furan-2-one) on mast cell degranulation induced by compound 48/80. Peritoneal mast cells from male adult Sprague-Dawley rats were purified in Percoll, preincubated in the presence of test lactones (dehydroleucodine, xanthatin or 3-benzyloxymethyl-5H-furan-2-one) and then challenged with the mast cell activator compound 48/80 (10 microg/ml). Concentration-response and kinetic studies of mast cell serotonin release evoked by compound 48/80, evaluation of mast cell viability and morphology by light and electron microscopy, and comparative studies using ketotifen and sodium chromoglycate were carried out. Serotonin release studies, carried out together with morphological studies, showed the effectiveness of the above lactones to stabilize mast cells. The comparative study with ketotifen and sodium chromoglycate, well known mast cell stabilizers, showed the following order of potency dehydroleucodine=xanthatin>3-benzyloxymethyl-5H-furan-2-one> or =ketotifen/sodium chromoglycate to inhibit mast cell serotonin release induced by compound 48/80. The present study provides the first strong evidence in favour of the hypothesis that dehydroleucodine, xanthatin and 3-benzyloxymethyl-5H-furan-2-one inhibit compound 48/80-induced serotonin release from peritoneal mast cells, acting thus as mast cell stabilizers. Our findings may provide an insight into the design of novel pharmacological agents which may be used to regulate the mast cell response.