No abstract

Dietary fibres consist of edible plant polysaccharides that are resistant to digestion and absorption in the human small intestine but undergo complete or partial fermentation in the colon. Seaweeds, notably Laminaria spp, are particularly rich in polysaccharides resistant to hydrolysis in the upper gastrointestinal tract and are, in consequence, considered as dietary fibres. Most of the carbohydrates from Laminaria spp are thought to be indigestible by humans. The main storage polysaccharide of these algae is laminarin, a β-polymer of glucose. The aims of this work were, on the one hand, to compare various methods of extraction of laminarin by partial characterisation of the product obtained and, on the other hand, to study the fate of this polysaccharide and its effects in the gastrointestinal tract in order to determine its potential as a dietary fibre in human nutrition. Among four methods tested to extract laminarin, the best appeared to be a hot HCl-based method. Human digestive enzymes did not hydrolyse laminarin, so this polysaccharide can be considered as a dietary fibre. After ingestion by rats, this polysaccharide was not found in faeces of these animals. It did not increase the intestinal transit and stool output in vivo, but it increased the contractile response of the stomach to acetylcholine in vitro.

A series of 3-alkylamino-4H-pyrido[2,3-e]-1,2,4-thiadiazine 1, 1-dioxides structurally related to diazoxide and pinacidil were synthesized and tested as possible K(ATP) channel openers on isolated pancreatic endocrine tissue as well as on isolated vascular, intestinal, and uterine smooth muscle. In contrast to previously described 3-alkylamino-4H-pyrido[4,3-e]-1,2,4-thiadiazine 1, 1-dioxides, most of the new compounds were found to be poorly active on B-cells but exhibited clear vasorelaxant properties. 3-(3, 3-Dimethyl-2-butylamino)-4H-pyrido[2,3-e]-1,2,4-thiadiazine 1, 1-dioxide (4d) and 7-chloro-3-(3, 3-dimethyl-2-butylamino)-4H-pyrido[2,3-e]-1,2,4-thiadiazine 1, 1-dioxide (5d), two compounds bearing the alkyl side chain of pinacidil, were found to be the most active representatives of their respective series on rat aorta rings. 3-Cycloalkylalkylamino- and 3-aralkylamino-7-chloro-4H-pyrido[2,3-e]-1,2,4-thiadiazine 1, 1-dioxides also expressed myorelaxant activity on electrically stimulated guinea pig ileum and on oxytocin-induced contractions of the rat uterus. Further biological investigations ((86)Rb efflux measurements, vasodilator potency on 30 and 80 mM KCl-induced contractions in the absence and presence of glibenclamide) revealed that compounds 4d and 5d, but not compound 5f, expressed the pharmacological profile of classical K(ATP) channel openers. In conclusion, by changing the position of the nitrogen atom in the pyridine ring, we now have obtained a family of drugs expressing an opposite tissue selectivity. Taken as a whole, the present findings also suggest that 3-alkylamino-4H-pyrido[2,3-e]-1,2,4-thiadiazine 1, 1-dioxides such as 4c, 4d, 5c, and 5d may be considered as new examples of K(ATP) channel openers expressing a pharmacological profile similar to that of pinacidil and diazoxide.