Pyrazine-Fused Triterpenoids Block the TRPA1 Ion Channel in Vitro and Inhibit TRPA1-Mediated Acute Inflammation in Vivo

TRPA1 is a nonselective cation channel, most famously expressed in nonmyelinated nociceptors. In addition to being an important chemical and mechanical pain sensor, TRPA1 has more recently appeared to have a role also in inflammation. Triterpenoids are natural products with anti-inflammatory and anticancer effects in experimental models. In this paper, 13 novel triterpenoids were created by synthetically modifying betulin, an abundant triterpenoid of the genus Betula L., and their TRPA1-modulating properties were examined. The Fluo 3-AM protocol was used in the initial screening, in which six of the 14 tested triterpenoids inhibited TRPA1 in a statistically significant manner. In subsequent whole-cell patch clamp recordings, the two most effective compounds (pyrazine-fused triterpenoids 8 and 9) displayed a reversible and dose- and voltage-dependent effect to block the TRPA1 ion channel at submicromolar concentrations. Interestingly, the TRPA1 blocking action was also evident in vivo, as compounds 8 and 9 both alleviated TRPA1 agonist-induced acute paw inflammation in mice. The results introduce betulin-derived pyrazine-fused triterpenoids as promising novel antagonists of TRPA1 that are potentially useful in treating diseases with a TRPA1-mediated adverse component

Panorametry: suggestion of a method for mandibular measurements on panoramic radiographs

<p>Abstract</p> <p>Background</p> <p>Orthopantomography (panoramic radiography) has been used for the study of measurements involving particularly the prediction of the eruption of impacted lower third molars and analyses of measurements of the ramus and head of mandible. The discrepancies involved with the projection of this radiographic image has stimulated the search for further ways to use it, particularly in orthodontic treatments and oral and maxillofacial surgeries. The author proposes a graphimetric method for the mandible, based on panoramic radiography. The results are expressed in linear and angular measurements, aiming at bilateral comparisons as well as the determination of the proportion of skeletal and dental structures, individually and among themselves as a whole. The method has been named Panorametry, and allows measurement of the mandible (Mandibular Panorametry) or the posterior mandibular teeth (Dental Panorametry). When combining mandible and maxilla, it should be referred to as Total Panorametry. It may also be used, in the future, with Cone Beam computed tomography (CT) images, and in this case it may be mentioned as CT Panorametry.</p

Discovery of Triterpenoids as Reversible Inhibitors of α/β hydrolase Domain Containing 12 (ABHD12)

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