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1.
J Physiol Pharmacol ; 67(4): 563-573, 2016 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-27779477

RESUMEN

Recent progress in endoscopic techniques has revealed that non-steroidal anti-inflammatory drugs (NSAIDs) often cause ulcers in the small intestine in humans, but effective therapy is not available at present. In the present study, we investigated the effects of feeding condition and the amount of dietary fiber (DF) in the diet on the formation of gastrointestinal ulcers induced by NSAIDs in dogs. Several types of diets containing various percentages of DF were given to dogs. Indomethacin (1 or 3 mg/kg, p.o.), ketoprofen (2 mg/kg, s.c.), or fulnixin (1 mg/kg, s.c.) was administered once daily at 10 a.m. after a morning meal or without a morning meal (fasted condition) for 3 - 7 days. Gastrointestinal lesions were examined 24 h after the final dose of the drugs. When indomethacin (3 mg/kg) was administered after a morning meal (fed condition) for 7 days, it produced many lesions in the small intestine. However, when it was given in the fasted condition without the morning meal, the lesions were markedly decreased. All the NSAIDs given after feeding of regular dry food containing 6% DF once a day for 3 days produced many lesions in the small intestine. The lesions were decreased or increased in dogs given prescription diets containing low DF (1.1%) and high DF (15.4%), respectively. Furthermore, lesions were not observed in dogs given canned diet containing very low DF (< 0.1%), whereas lesions appeared again in dogs given canned diet supplemented with cellulose (3 or 10%) but not with pectin (10%). These results suggested that both feeding condition and insoluble DF, such as cellulose in the diet, play an important role in the formation of NSAID-induced small intestinal lesions, and that a diet with no or low amounts of DF may decrease gastrointestinal side-effects associated with the use of NSAIDs.


Asunto(s)
Antiinflamatorios no Esteroideos/efectos adversos , Fibras de la Dieta/farmacología , Enfermedades Intestinales/inducido químicamente , Intestino Delgado/efectos de los fármacos , Úlcera/inducido químicamente , Animales , Celulosa/farmacología , Suplementos Dietéticos , Perros , Femenino , Indometacina/efectos adversos , Enfermedades Intestinales/patología , Intestino Delgado/patología , Cetoprofeno/efectos adversos , Masculino , Pectinas/farmacología , Estómago/efectos de los fármacos , Estómago/patología , Gastropatías/inducido químicamente , Gastropatías/patología , Úlcera/patología
2.
Gan To Kagaku Ryoho ; 13(4 Pt 2): 1163-8, 1986 Apr.
Artículo en Japonés | MEDLINE | ID: mdl-2425741

RESUMEN

The authors examined the sensitivities of esophageal cancer to Bleomycin (BLM), Peplomycin (PEP), Cisplatin (CDDP) and 5-FU by the INAS method using 3H-thymidine or 14C-formate as labeled precursors, and determined the concentrations of anticancer agents in cancer lesions by the Band Culture method. On the other hand, the authors investigated the superiority or inferiority of various methods of BLM administration by observing the prevention effect of BLM on the development of experimental esophageal cancer in rats. Forty-three cases out of 76, 57%, showed a sensitivity to BLM, 60% to PEP, 38% to CDDP and 56% to 5-FU. As to the types of roentgenological findings, the superficial and tumorous types showed a high sensitivity rate. As to the types of macroscopical findings, the protruded and superficial types showed a high sensitivity rate. As to the types of histological findings, well differentiated squamous cell carcinoma showed a high sensitivity rate. Sensitivity was higher in metastatic lymph nodes than in main cancer lesions. Tumor tissues which had undergone previous hyperthermic management (at 42 degrees C) showed a higher sensitivity than those which had not. PEP at a half dose brought about the same grade of anticancer effect as BLM. The sensitivities of esophageal cancer to various anticancer agents showed individual differences among clinical cases. Therefore, combination chemotherapy for esophageal cancer was thought to be an effective administration method. The divided administration of small doses of BLM was thought to be more superior than the one-shot administration of a large dose for esophageal cancer. The results of the INAS sensitivity test were perfectly coincident with the effects of chemotherapy in clinical cases of esophageal cancer.


Asunto(s)
Antineoplásicos/farmacología , Evaluación Preclínica de Medicamentos/métodos , Neoplasias Esofágicas/terapia , Animales , Antineoplásicos/administración & dosificación , Bleomicina/farmacología , Radioisótopos de Carbono , Terapia Combinada , ADN de Neoplasias/biosíntesis , Perros , Humanos , Metástasis Linfática/tratamiento farmacológico , Ratones , Ratones Desnudos , Tritio
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