Short-chain fatty acids induce cytoskeletal and extracellular protein modifications associated with modulation of proliferation on primary culture of rat intestinal smooth muscle cells.

Short-chain fatty acids are the main end products of bacterial fermentation of carbohydrates. Their role on the metabolism and biology of colonocytes is now well characterized. However, the functional consequences of their presence on intestinal smooth muscle cells remain poorly studied. We aimed to assess the effect of different short-chain fatty acids on ileal and colonic smooth muscle cells in primary culture and on A7R5 line. Butyrate (above 0.1 mM) inhibited A7R5 cell proliferation, while at low concentration (0.05 to 0.5 mM) butyrate significantly stimulated the proliferation of ileal and colonic myocytes in primary culture. An inhibition was observed at higher concentrations. Collagenous and noncollagenous protein synthesis was stimulated by butyrate. Moreover, butyrate stimulated actin and myosin expression. Thus, butyrate, which is produced by dietary fiber fermentation, may affect intestinal muscles by directly acting at the molecular level on myocytes.

Comparison of the effect of different short chain fatty acids on the growth and differentiation of human colonic carcinoma cell lines in vitro.

The aim of this study was to compare the effects of acetate, propionate, butyrate, iso-butyrate, valerate, iso-valerate and caproate on cell growth and on the activities of alkaline phosphatase (AP) and dipeptidyl aminopeptidase IV (DPP IV) by three human colonic adenocarcinoma cell lines. In addition to butyrate, propionate and valerate inhibited cell proliferation of the three cell lines. The other SCFAs did not influence cell proliferation. AP and DPP IV activities were strongly stimulated by butyrate on two of the three cell lines. On HT-29, AP was strongly stimulated, however DPPIV expression remained undetectable. Propionate and valerate exhibited a weaker stimulation, the other SCFAs being ineffective. The effect of SCFAs on cell proliferation and differentiation clearly depends on the number of carbons and on the configuration of the basic structure of the molecule.

Valproate therapy induces von Willebrand disease type I.

To investigate the increased tendency of hemorrhage in patients receiving valproate (VPA) therapy, we studied coagulation parameters in 30 randomized children of a group of 83 children receiving antiepileptic drug (AED) therapy. Besides a reduction in fibrinogen concentration and platelet count, we observed a significant decrease in factor VIII-complex. A decrease in factor VIII:C was noted in 33%, a decrease in von Willebrand factor (vWF:Ag) was noted in 83% and a decrease in ristocetin-cofactor activity (vWF:Rcof) was noted in 66% of the children. We classified a von Willebrand syndrome type I in 67% of our patients receiving VPA therapy. Sixty-three percent of patients had a history of bleeding, and 23% had a prolonged bleeding time. We compared our results with those of a control group and of a group of patients with congenital von Willebrand disease (vWD), from which patients with multimer types II and III were excluded. Because coagulation parameters in patients with congenital vWD are similar to those receiving AED therapy, we designated the increased tendency to hemorrhage as VPA-induced vWD. The decrease in coagulation parameters were not dependent on either VPA dose or period of administration. In patients receiving VPA therapy, this result must be considered, especially during surgical intervention and after traumatic events.