Prostaglandin E2 Receptor EP4 Inhibition Contracts Rat Ductus Arteriosus.

BACKGROUND: Patent ductus arteriosus (PDA) is common in premature infants. Cyclooxygenase inhibitors such as indomethacin, which inhibit prostaglandin E2(PGE2) synthesis, are currently the sole treatments for patients with PDA. Their efficacy are, however, frequently limited, and adverse effects are problematic. Because the PGE2-specific receptor EP4 selectively expresses in rat ductus arteriosus (DA), it is hypothesized that EP4 inhibition would promote DA closure with fewer side-effects.Methods and Results:A new chemical compound EP4 antagonist, RQ-15986 (renamed from CJ-042794), was used. Whether RQ-15986 selectively contracted the DA was examined by measuring the isometric tension of rat DA ex vivo at embryonic day 19 (e19) and e21. RQ-15986 at a dose of 10-6mol/L increased the isometric tension of the DA up to 44.8±6.2% and 69.1±12.9% to the maximal KCl-induced tension at e19 and e21 respectively. The effect of RQ-15986 on rat DA in vivo was also tested by using a rapid whole-body freezing method. RQ-15986 inhibited PGE1-induced DA dilatation in neonatal rats. Furthermore, RQ-15986 contracted the DA in a dose-dependent manner, and the constriction was greater at e21 than at e19. Moreover, RQ-15986 did not contract the aorta or the marginal artery of the colon. CONCLUSIONS: EP4 inhibition contracts rat DA with fewer side-effects. EP4 inhibition is a promising alternative strategy to treat patients with PDA.

Use of a Novel Device to Assess Intraoral and Intrapharyngeal Baropressure during Sound Production.

OBJECTIVE: We developed a novel device that simultaneously measures oral and intrapharyngeal baropressure. The transducer has the advantage that it can be placed in any region. We determined the effect of different speech samples on baropressure in these regions. PATIENTS AND METHODS: Seven healthy individuals produced speech samples comprising vowels and consonants (e.g., /aka/, /apa/, and /ash/). Two transducers were installed into the experimental plate at the incisive papillae and center of the Ah-line; a third transducer was placed in the mid-pharyngeal cavity. During each task, 3 parameters were analyzed: peak pressure, mean pressure, and the temporal relationship between sound signals and pressure changes. RESULTS: The mean pressure did not change during the production of a single vowel; however, the pressure transiently increased during the production of the speech samples, depending on the place of articulation. Moreover, the place of articulation affected the onset and peak timing of pressure changes. CONCLUSIONS: These findings indicate that pressure changes during the production of speech samples reflect the functional aspects of speech production. In particular, simultaneous pressure recordings at multiple locations would provide precise information about speech production, compared to pressure studies that used a single pressure transducer.