Silymarin can be extracted from the milk thistle, and silibinin is the main component of the plant extract. Possibly due to their antioxidant and membrane-stabilizing properties, the compounds have been shown to protect different organs and cells against a number of insults. Thus liver, kidney, erythrocytes and platelets have been protected from the toxic effects of ethanol, carbon tetrachloride, cold ischemia and drugs, respectively. The effect of silibinin on endocrine and exocrine pancreas, however, has not been studied. We therefore investigated whether silibinin treatment attenuates cyclosporin A (CiA) toxicity on rat endocrine and exocrine pancreas. Groups of 15 male Wistar rats were treated for 8 days with CiA and/or silibinin. On day 9, endocrine and exocrine pancreatic functions were tested in vitro. At the end of the treatment period, blood glucose levels in vivo were significantly higher in rats treated with CiA while silibinin did not affect glucose levels. In vitro, insulin secretion was inhibited after treatment with silibinin, but amylase secretion was not affected. After treatment with CiA both insulin and amylase secretion were reduced. Silibinin and CiA had an additive inhibitory effect on insulin secretion, but silibinin attenuated CiA-induced inhibition of amylase secretion. Despite CiA treatment, amylase secretion was in fact restored to normal with the highest dose of silibinin. Thus silibinin inhibits glucose-stimulated insulin release in vitro, while not affecting blood glucose concentration in vivo. This combination of effects could be useful in the treatment of non-insulin-dependent diabetes mellitus. Furthermore, silibinin protects the exocrine pancreas from CiA toxicity. As this inhibitory effect is probably unspecific, silibinin may also protect the exocrine pancreas against other insult principles, such as alcohol.
Background-Meals disrupt the interdigestive pattern of small bowel motor activity and convert it into the postprandial pattern. Previous studies have shown that duration of postprandial motor activity depends on the caloric value of a meal, but results from two recent human studies suggested that there is a caloric ceiling, above which an additional increase in the caloric load fails to prolong the postprandial period further. Aim-To investigate the hypothesis of a caloric ceiling by studying daytime motor activity of the human small bowel in response to five solid meals, covering a wide range of calories. Methods-Eight healthy male volunteers underwent five separate, ambulatory small bowel manometry studies and had a total of 80 meals. For lunch, volunteers ate between one and five portions of a solid meal (220, 440, 660, 880, or Two distinct motor patterns have been described in the canine and the human small bowel. Mainly for technical reasons, over the past two decades research has strongly focused on the interdigestive pattern, but recent advances in recording techniques and data analysis now allow the study of postprandial contractile activity. Motor activity of the small bowel can now be recorded in ambulatory subjects for prolonged periods, a prerequisite for detailed analysis of total postprandial motility, and computer programs have been validated that analyse pressure recordings objectively and rapidly.' 2There are very few studies on postprandial motility, and almost all of these have been performed in strictly controlled animal physiology laboratories. In dogs, Schang et al and de Wever et al have shown that duration of postprandial motor activity depends on the caloric value of a meal.3 ' In humans, Ouyang et al and our group have shown the same phenomenon for liquid and solid meals,5 6 whereas Soffer and Adrian were recently unable to show a longer postprandial pattern after ingestion of higher caloric loads.7The discrepancies between the three human studies5-7 could be reconciled by postulating a caloric ceiling above which an additional increase in the caloric load does not further prolong duration of postprandial motor activity. We therefore investigated daytime motor activity of the human small bowel in response to five solid meals, covering a wide range of calories. As volunteers had the same meals for lunch and as a late night dinner, we were also able to compare daytime and night time contractile activity. A previous study from our group showed that the postprandial interval is shorter during sleep, suggesting that activity of the central nervous system regulates not only interdigestive but also postprandial motility of the small bowel.Using 24 hour ambulatory manometry for data acquisition and a validated computer program for data analysis, we measured duration of the postprandial motor pattern, and also calculated incidence and amplitude of contractions over the total postprandial period. These data on postprandial motor motility of the normal human small bowel could serve as a...
The presence of acid in the oesophagus has been shown to stimulate salivary secretion, but the relevance of this oesophago-salivary reflex for acid clearance in physiological and pathological gastro-oesophageal reflux (GOR) is unknown. This study was designed to investigate the interrelation between oesophageal acid and both resting and stimulated salivary secretion. In 10 healthy volunteers, the acid clearance times after bolus infusion of 20 ml of 0.1 N hydrochloric acid were measured by means of ambulatory oesophageal pH monitoring. With a constant swallowing rate and resting salivary flow, the acid clearance time was significantly longer with dry as opposed to wet swallows (12.6 ± 2.6 vs. 6.9 ± 1.9 min; p = 0.01). When the salivary flow was doubled by chewing a gum base (26.0 ± 3.4 vs. 13.2 ± 2.0 ml/l5 min; p = 0.005), the acid clearance time was markedly shortened (6.9 ± 1.9 vs. 2.3 ± 0.2 min; p = 0.02). As compared with water control, salivary flow, pH, and protein content were not affected by a bolus infusion of hydrochloric acid. This was true both for resting and gum-stimulated salivary secretion. Our study suggests that an oesophago-salivary reflex becomes effective only in prolonged episodes of GOR. This may explain why the water brash phenomenon is not regularly experienced by all reflux patients. Our study also suggests that chewing gum might be a non-pharmacological treatment option for some patients with symptomatic GOR.
Interdigestive motor activity has been studied extensively both in the human and canine small intestine. The more irregular postprandial pattern, however, has rarely been studied. In particular, physiological studies in humans are lacking. Thus it is unknown whether the physical state of a meal affects the duration of the postprandial motor activity or contractile activity during the postprandial period. 8 healthy male volunteers, aged 19-38 years, underwent a single ambulatory 24-hour manometry study. During the study, volunteers had two physiological meals. The solid meal consisted of pasta with vegetables, and the liquid meal was a vanilla milk drink. The two meals were both palatable, isocaloric (660 kcal) and had an identical fat content (32%). Recordings were analyzed visually for phase III of the migrating motor complex and a validated computer program calculated the mean frequency and amplitude of contractions as well as the mean area under the curve (AUC). The postprandial period was significantly shorter after the liquid meal compared to the solid meal (196 ± 43 vs. 298 ± 23 min; p < 0.04). During the postprandial period, the mean incidence of contractions (2.0 ± 0.5 vs. 3.7 ± 0.4 min-1; p < 0.02) and the mean AUC (132 ± 32 vs. 236 ± 27 mm Hg × s × min-1; p < 0.02) were significantly lower after the liquid meal. The mean amplitude of contractions during the total postprandial period, however, was not significantly different between the two test meals (19.3 ± 0.6 vs. 18.6 ± 0.8 mm Hg). We conclude that human small bowel motor activity differs markedly between solid and liquid meals. Thus the postprandial pattern persists longer after solid meals, and this may have been due to the slower gastric emptying of solids as opposed to liquids. Furthermore the small bowel contracts far more frequently after solid meals.
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