Slow gastric emptying in patients with type I diabetes seems related to the degree of autonomic neuropathy but not to peripheral neuropathy, actual blood glucose, and glycemic control.
This crossover, double-blind study investigated the effects of single oral doses of the prodrug loperamide oxide, which is reduced gradually to loperamide in the intestine, and loperamide on jejunal motor activity in 12 fasting healthy men. Five minutes after a phase III of the migrating motor complex (MMC), 2 mg loperamide oxide, 4 mg loperamide oxide, 4 mg loperamide, or placebo were administered. Thereafter, motor activity 10-30 cm abroad the ligament of Treitz was recorded with five catheter orifices at 3-cm intervals over 4 hr. Number of contractions and area under curve increased significantly with 4 mg loperamide and 4 mg loperamide oxide, the increases with loperamide oxide occurring more gradually. Placebo and 2 mg loperamide oxide had no discernible effects. With both 4 mg loperamide and 4 mg loperamide oxide, phase I of the MMC was slightly prolonged and phase II and the time from drug administration to the onset of the first phase III slightly shortened. The percentage of aborally propagated contractions in phase II increased with all active treatments, whereas the occurrence of phases III was not altered.
Pharyngoesophageal disorders may be sensed only vaguely, inducing the globus sensation. Psychological and psychiatric characteristics could be relevant to the discomfort experienced but are unlikely to be etiologically significant.
The intervening sequences of nuclear tRNA precursors are known to be excised by tRNA splicing endonuclease. We show here that a T7 transcript corresponding to a pre-tRNA(Tyr) from Arabidopsis thaliana has a highly specific activity for autolytic intron excision. Self-cleavage occurs precisely at the authentic 3'-splice site and at the phosphodiester bond one nucleotide downstream of the authentic 5'-splice site. The reaction results in fragments with 2',3'-cyclic phosphate and 5'-OH termini. It is resistant to proteinase K and/or SDS treatment and is not inhibited by added tRNA. The self-cleavage depends on Mg2+ and is stimulated by spermine and Triton X-100. A set of sequence variants at the cleavage sites has been analysed for autolytic intron excision and, in parallel, for enzymatic in vitro splicing in wheat germ S23 extract. Single-stranded loops are a prerequisite for both reactions. Self-cleavage not only occurs at pyrimidine-A but also at U-U bonds. Since intron self-excision is only about five times slower than the enzymatic intron excision in a wheat germ S23 extract, we propose that the splicing endonuclease may function by improving the preciseness and efficiency of an inherent pre-tRNA self-cleavage activity.
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