A randomized phase 2 study of the 5-HT receptor agonist felcisetrag for postoperative gastrointestinal dysfunction after bowel surgery.

Background: Felcisetrag (5-hydroxytryptamine-4 receptor [5-HT] agonist) is under investigation as prophylaxis or active treatment for accelerating resolution of gastrointestinal function post-surgery.

Methods: Phase 2, randomized, placebo-controlled, parallel five-arm, double-blind, multicenter study (NCT03827655) in 209 adults undergoing open or laparoscopic-assisted bowel surgery. Patients received intravenous placebo, felcisetrag 0.

Covariate adjusted meta-analytic predictive (CA-MAP) prior for historical borrowing using patient-level data.

Utilization of historical data is increasingly common for gaining efficiency in the drug development and decision-making processes. The underlying issue of between-trial heterogeneity in clinical trials is a barrier in making these methods standard practice in the pharmaceutical industry. Common methods for historical borrowing discount the borrowed information based on the similarity between outcomes in the historical and current data.

Heritable translocation and dominant-lethal mutation induction with ethylene oxide in mice.

Ethylene oxide was studied for induction of dominant-lethal mutations and heritable translocations in male mice. The chemical was prepared in water and injected intraperitoneally. The dominant-lethal study was conducted using a single injection of 150 mg/kg (maximum tolerated dose); in the heritable translocation study males were injected daily on weekdays for 5 weeks with 60 or 30 mg/kg dose per day.

Sequence position of 3-hydroxyproline in basement membrane collagen. Isolation of glycyl-3-hydroxyprolyl-4-hydroxyproline from swine kidney.

The position of 3-hydroxyproline was investigated in the triplet sequences of peptides released by collagenase digestion of a collagen preparation from kidney cortex. Composition of the collagen preparation indicated that it was largely or wholly of basement membrane origin. 3-Hydroxyproline was detected in only one sequence, the tripeptide, glycyl-3-hydroxyprolyl-4-hydroxyproline, which accounted for a major fraction of the total 3-hydroxyproline obtained in the peptides released by collagenase.

Properties of the inducible hydroxyproline transport system of Pseudomonas putida.

Features of the transport system for hydroxyproline in a strain of Pseudomonas putida were studied. A mutant, lacking hydroxyproline-2 epimerase and unable to metabolize hydroxy-l-proline, was shown to transport and accumulate this compound after induction. Both entry and exit rates were examined, and kinetic constants for the reaction were determined.

Inducible degradation of hydroxyproline in Pseudomonas putida: pathway regulation and hydroxyproline uptake.

Studies in Pseudomonas putida of the inducible degradation of hydroxyproline to alpha-ketoglutarate have indicated that either of the two epimers, hydroxy-l-proline or allohydroxy-d-proline, acts as an inducer of all the pathway enzymes. In a mutant lacking the first enzyme of the sequence, hydroxyproline-2-epimerase, which interconverts these two hydroxyproline epimers, either epimer is still equally active as an inducer of the remaining three enzymes, suggesting that each epimer has intrinsic inducer activity. The second and third enzymes of the sequence were induced coordinately.