RESUMEN
The HT4-agonist Cisapride (CIS) and the peripheral D2-antagonist Domperidone (DOMP) have distinct prokinetic actions. We compared their clinical efficacy in 127 dyspeptic patients. Patients with upper abdominal complaints of > 1 month duration, who had a normal UGE were allocated to the REFLUX-group (RG), (predominance of heartburn, acid regurgitation or retrosternal pain) or if devoid of this specific symptomatology to the DYSPEPSIA-group (DG) In a double-blind randomised fashion and allocated to 10 mg CIS or 20 mg DOMP qid (RG) or tid (DG) for 1 month and followed-up for further 2 months. In RG (N = 43, p < 0.05) the response rates were clearly in favour of CIS, but not in DG (N = 84). In RG DOMP was more effective against nausea. The benefit of both therapies was largely maintained in the follow-up period. Cisapride and domperidone were effective in the treatment of dyspepsia. Cisapride was more effective than domperidone in the REFLUX-Group.
Asunto(s)
Antiulcerosos/uso terapéutico , Domperidona/uso terapéutico , Dispepsia/tratamiento farmacológico , Reflujo Gastroesofágico/tratamiento farmacológico , Fármacos Gastrointestinales/uso terapéutico , Piperidinas/uso terapéutico , Adulto , Antiulcerosos/efectos adversos , Cisaprida , Domperidona/efectos adversos , Método Doble Ciego , Femenino , Estudios de Seguimiento , Fármacos Gastrointestinales/efectos adversos , Humanos , Masculino , Persona de Mediana Edad , Piperidinas/efectos adversos , Resultado del TratamientoRESUMEN
Surgical diversion of bile and pancreatic secretions to the mid small bowel has been shown to provoke increased CCK plasma concentration and growth of the pancreas in rats. This study was undertaken to investigate the effects of chronic pancreaticobiliary diversion on pancreatic morphology as well as the circulating concentrations of pancreatic polypeptide, secretin, gastrin, and CCK. Fifteen month diversion provoked 73 and 86% increases in pancreatic weight and volume (p less than 0.001). Cholecystokinin blood concentration increased by 98%, from 20.9 +/- 5.7 pg/ml in controls to 41.3 +/- 5.4 after diversion (p less than 0.05), but pancreatic polypeptide, secretin, and gastrin levels were not affected. The volume of the exocrine pancreas doubled from 1104.6 +/- 78.2 mm3 in controls to 2201.2 +/- 229.2 (p less than 0.001), with a matching increase in interstitial tissue. On the contrary, the volume of the endocrine pancreas remained unchanged. Hyperplastic nodules developed in the exocrine pancreas, in 71% of diverted rats, but not in transected controls. We conclude from these observations that chronic diversion of bile and pancreatic juice stimulated pancreatic growth, most likely through a persistent rise of CCK plasma concentrations. Furthermore, this long lasting stimulation induced the development of exocrine pancreatic nodules.
Asunto(s)
Bilis/fisiología , Colecistoquinina/sangre , Páncreas/fisiología , Jugo Pancreático/fisiología , Neoplasias Pancreáticas/etiología , Animales , Hiperplasia/sangre , Hiperplasia/etiología , Masculino , Ratas , Ratas Endogámicas , Factores de TiempoRESUMEN
The evidence for an enteropancreatic trophic axis is reviewed. Luminal nutrition is essential for the maintenance of normal intestinal mucosal, as well as exocrine pancreatic structure and function. Exclusion of luminal nutrition leads to mucosal hypoplasia and hypofunction with similar changes in the pancreas. The trophic effect of luminal nutrition may be mediated through the release of regulatory peptides with endocrine or paracrine effects. Enteroglucagon is the strongest candidate for the role of "enterotrophin" while cholecystokinin (CCK) markedly influences pancreatic growth. Thus, CCK not only stimulates exocrine pancreatic secretion but makes acinar cells divide and the pancreas grow. The cellular mechanisms whereby trophic peptides influence normal and adaptive growth are also discussed with emphasis on polyamines (putrescine, spermidine and spermine) and the key enzymes controlling their synthesis (ornithine decarboxylase [ODC]) and degradation (diamine oxidase [DAO]). When polyamine synthesis is blocked with the ODC inhibitor difluoromethyl ornithine (DFMO), the adaptive intestinal hyperplasia of pancreaticobiliary diversion is either inhibited or completely prevented. A proposed sequence of events might be: luminal nutrients, particularly long chain fat, reach the ileum and colon and stimulate increased enteroglucagon release. Enteroglucagon binds to cell receptors and triggers an intracellular cascade involving ODC and the polyamines which, in turn, stimulate RNA polymerase, DNA, RNA and protein synthesis, cell division and adaptive tissue growth.
Asunto(s)
Fenómenos Fisiológicos del Sistema Digestivo , Hormonas Gastrointestinales/fisiología , Páncreas/fisiología , Poliaminas/fisiología , Adaptación Fisiológica , Animales , Colecistoquinina/fisiología , Perros , Eflornitina , Péptidos Similares al Glucagón/fisiología , Humanos , Fenómenos Fisiológicos de la Nutrición , Ornitina/análogos & derivados , Ornitina/farmacología , Inhibidores de la Ornitina Descarboxilasa , Páncreas/crecimiento & desarrollo , RatasRESUMEN
Beside intraluminal factors, humoral agents play an important role in intestinal adaptation. Enteroglucagon, the mucosal concentration of which is maximal in the terminal ileum and colon, is the strongest candidate for the role of small intestinal mucosal growth factor. The present experiment was designed to study the role of colonic enteroglucagon in stimulating mucosal growth in rats with a normal small intestine. After eight days of glucose large bowel perfusion, enteroglucagon plasma concentrations were 120.7 +/- SEM 9.2 pmol/l, versus 60.1 +/- 6.8 in mannitol perfused control rats (p less than 0.001). Gastrin, cholecystokinin, neurotensin, pancreatic glucagon, and insulin plasma concentrations were unchanged. Crypt cell proliferation, measured by the vincristine metaphase arrest technique, increased significantly in the small intestine of glucose perfused animals (p less than 0.005-0.001) in comparison with the controls. This resulted in a greater mucosal mass in both proximal and distal small bowel: mucosal wet weight, DNA, protein and alpha D-glucosidase per unit length intestine were all significantly higher (p less than 0.05-0.001) than in mannitol perfused rats. Our data, therefore, support the hypothesis that enteroglucagon is an enterotrophic factor and stress the possible role of the colon in the regulation of small bowel trophicity.
Asunto(s)
Colon/metabolismo , Hormonas Gastrointestinales/sangre , Péptidos Similares al Glucagón/sangre , Glucosa/farmacología , Mucosa Intestinal/patología , Intestino Delgado/patología , Animales , Peso Corporal/efectos de los fármacos , División Celular/efectos de los fármacos , Hormonas/sangre , Hiperplasia/sangre , Hiperplasia/metabolismo , Hiperplasia/patología , Masculino , Tamaño de los Órganos/efectos de los fármacos , Perfusión , Ratas , Ratas EndogámicasRESUMEN
Pancreatico-biliary diversion (PBD) stimulates pancreatic growth in the rat. The present experiment was designed to investigate the mechanism of this phenomenon. The potential roles of endogenous CCK, gastrin, and secretin were studied. Hormone measurements by specific RIA's show that PBD was associated with higher CCK plasma concentrations and, conversely, with lower gastrin circulating levels. Secretin and pancreatic polypeptide were unaffected by PBD. Seven days' subcutaneous administration of proglumide (1000 mg/kg/day), benzotript (100 mg/kg/day), two CCK and gastrin receptor antagonists, and Ranitidine (100 mg/kg/day) resulted in a significant inhibition of PBD-induced pancreatic growth, assessed by measurements of pancreatic weight, DNA, RNA and protein content. These results suggest, therefore, that CCK plays a central role in the development of the pancreatic adaptive response to PBD.