[Lactate acidosis after 5 days of phenformin therapy].
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Biomedical subjects
Publications and source records attributed to H Ruppin.
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Myoelectric activity induced by a synthetic analogue of the duodenal polypeptide motilin, was studied in isolated vascular-perfused canine duodenum and stomach, and in conscious dogs with serosal electrodes implanted in the stomach and the small intestine. In the isolated preparation, the duodenum was found to be four times as sensitive as the antrum to the polypeptide, showing a dose-dependent increase in spike activity within two minutes after administration of the polypeptide. By contrast, in the conscious fasted animal, the only response to motilin, above a threshold dose, was the interpolation of a premature migrating myoelectric complex in the spontaneous interdigestive sequence, appearing fifteen to twenty minutes after the start of infusion. Since the essential difference between the ex vivo and the intact intestine was the preservation of efferent and afferent nervous connections in the latter, it seems that in the conscious animal, the response to exogenous motilin is modulated by the innervation of the intestine, or, alternatively, motilin interacts with the centre controlling the pattern of motor activity in the small intestine rather than directly with smooth muscle. The latter hypothesis is supported by the observation that motilin had no effect on the motor activity of the small intestine during the infusion of pentagastrin which abolishes spontaneous migrating myoelectric complexes.
In 6 female subjects without gastrointestinal diseases, 13-norleucine motilin (13-Nle-M) synthetic and biological analogue of the duodenal polypeptide, motilin, caused acceleration of intestinal transit time. Intravenous infusion of 0.4 mug/kg-h of 13-Nle-M reduced mean transit time by 50 percent. No side effects occurred during infusion of the polypeptide. Radiographic appearance of small intestinal peristalsis and mucosal relief was not influenced by 13-Nle-M.
Synthetic 13-norleucine-motilin (13-nle-motilin), structural and biological analogue of the naturally-occurring duodenal polypeptide, motilin, is known to stimulate antral and duodenal motor activity in vitro, but delays gastric emptying in man. In this study the direct actions of the synthetic polypeptide on myoelectrical activity and intraluminal pressure have been studied in the isolated vascular-perfused canine stomach and duodenum. 13-nle-motilin increased intraluminal pressure in the pylorus and duodenum, and dose-response analysis showed the duodenum to be twice as sensitive as the pylorus to the polypeptide. Pressure changes in the antrum were small and not dose-related, but, whereas the basic electrical rhythm in the duodenum was not altered, slow wave frequency, rhythm, and propagation in the antrum were disturbed. Electronic analysis of the duodenal spike increase which accompanied pressure rises demonstrated correlations between increases in spikes, intraluminal pressure, and dose. These results show that the direct effect of the polypeptide on adjacent organs may explain the combination of increased motor activity with delayed gastric emptying as a consequence of disturbance in the co-ordination between antrum, pylorus, and duodenum.
In this study, the effect of 13-norleucine motilin (13-Nle-M) on post-cholecystectomy ileus was assessed in 6 female patients. 13-Nle-M given by continuous i.v. infusion (0.4 mug/kg-h) on the second and third day following surgery did not influence the manifestation and duration of intestinal paralysis in comparison to 6 control patients treated with 0.9% saline. Bowel sounds, however, were more pronounced in the 13-Nle-M-group. Blood pressure and pulse rate were not influenced by the polypeptide, and no other side effects were seen, either.
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In 3 healthy male volunteers, graded doses of 13-norleucine-motilin (13-nle-motilin)--synthetic analogue of motilin and biologically equivalent to the natural polypeptide--were given intravenously on separate days. Gastric emptying, as determined by means of a radioisotope method, was slowed down dose-dependently by increasing doses of 13-nle-motilin. This was indicated by increasing "half-lives" and "starting indices" of the gastric emptying process, and by decreasing pyloric loss rates, respectively. The gastric pepsin output rose markedly from the basal level during intravenous infusion of 13-nle-motilin.
Dermatitis herpetiformis (DH) has been reported to be associated with various degrees of intestinal villous atrophy in 19 to 68 percent of the cases studied. This was true particularly in British and American populations. The present investigation deals with morphological and functional characteristics of small intestinal mucosa in a group of German DH patients (n=16): No case of villous atrophy could be detected, whereas interepithelial lymphocytes were shown to be slightly but significantly elevated. Intestinal disaccharidase activities were not statistically different from those of healthy control subjects, and oral lactose tolerance tests were normal in each of 8 patients tested. Genetical and immunological differences between our DH patients and those studied by British and American authors may be responsible for the basically different results as to "dermatogenic enteropathy".
In conscious fasted dogs, with chronically-implanted electrodes in stomach and small intestine, typical aborally-propagated interdigestive myoelectric complexes were induced by the infusion of 13-nor-leucine motilin (13-Nle-M); whereas when the normal interdigestive activity was abolished by the infusion of pentagastrin, the resulting 'postprandial' pattern of activity was not significantly modified by the administration of 13-Nle-M. Results from this study provide further evidence that Motilin as well as Gastrin may be involved in the control of gastrointestinal motility in dogs.
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