DA-9701 improves colonic transit time and symptoms in patients with functional constipation: A prospective study.

BACKGROUND AND AIM: DA-9701, a newly developed prokinetic agent formulated with Pharbitis Semen and Corydalis Tuber, has been shown to effectively treat functional dyspepsia. Recently, it has also been suspected to improve gastrointestinal motor function. The aims of this study were to assess the effect of DA-9701 on colonic transit time (CTT) and symptoms of functional constipation. METHODS: Thirty-three patients with functional constipation based on the Rome III criteria were prospectively enrolled. The patients received 30-mg DA-9701 three times a day for 24 days. CTT was estimated initially and at the end of treatment. Symptoms such as spontaneous bowel movements, straining, stool form, feeling of incomplete emptying and anorectal blockage, abdominal discomfort and pain, overall defecation satisfaction, and incidence of adverse events were also analyzed. RESULTS: Twenty-seven patients completed the study. DA-9701 was associated with a significantly reduced CTT from 34.9 ± 17.6 to 23.7 ± 19.1 h (P = 0.001). Segmental CTT also significantly decreased after treatment (right CTT: from 16.8 [0.0-28.8] to 6.0 [0.0-25.2] hours, P < 0.001; rectosigmoid transit time: from 13.2 [0.0-38.4] to 6.0 [0.0-33.6] hours, P = 0.021). In addition, all constipation-related subjective symptoms, including spontaneous bowel movement frequency, significantly improved compared with those before treatment. Serious adverse events did not occur. CONCLUSIONS: DA-9701 accelerates colonic transit and safely improves symptoms in patients with functional constipation. Therefore, we suggest that this novel agent could help to treat patients with this condition.

A transcription terminator in the groEx gene of symbiotic X-bacteria expressed in Escherichia coli.

The over-expressing groEx gene of symbiotic X-bacteria in Amoeba proteus has unique nucleotide motifs (Tx), containing two hairpins and a C-rich region at its 3'-end. To investigate the role of Tx as a transcription terminator, we mutated Tx and analyzed the effects on the expression of an upstream-located lacZ in E. coli. The level of beta-galactosidase (beta-gal) production in Tx deletion mutants was reduced to 23% of the control level. Site-directed mutation of the hairpin-1, C-rich region, and hairpin-2 reduced the beta-gal production to 28-64%, 33, and 20% of wild-type Tx, respectively. The amount of lacZ transcripts that were detected in RNA blots was proportional to the level of beta-gal. The Tx sequence had 97% termination efficiency in vivo, and the mutations in Tx resulted in read-through transcripts with significantly shortened half-life. In rho- E. coli, the level of the beta-gal production by Tx was reduced to 15% of that in rho+ E. coli. These results suggest that Tx is a Rho-dependent transcription terminator. Also, hairpin-2 is the most effective component among the three motifs of Tx for proper termination of the transcription and stability of mRNAs.