Long-term dexamethasone treatment diminishes store-operated Ca^(2+) entry in salivary acinar cells

Corticosteroids are used in the treatment of many diseases; however, they also induce various side effects. Dexamethasone is one of the most potent corticosteroids, and it has been reported to induce the side effect of impaired salivary gland function. This study aimed to evaluate the effects of dexamethasone on mouse submandibular gland function to gain insight into the mechanism of dexamethasone-induced salivary hypofunction. The muscarinic agonist carbachol(CCh) induced salivary secretion and was not affected by short-term dexamethasone treatment but was decreased following long-term dexamethasone administration. The expression levels of the membrane proteins Na^+-K^+-2 Cl-cotransporter, transmembrane member 16 A, and aquaporin 5 were comparable between the control and long-term dexamethasone treatment groups. The CCh-induced increase in calcium concentration was significantly lower in the presence of extracellular Ca^(2+) in the long-term dexamethasone treatment group compared to that in the control group. Furthermore, CCh-induced salivation in the absence of extracellular Ca^(2+) and Ca^(2+) ionophore A23187-induced salivation was comparable between the control and long-term dexamethasone treatment groups.Moreover, salivation induced by the Ca^(2+) -ATPase inhibitor thapsigargin was diminished in the long-term dexamethasone treatment group. In summary, these results demonstrate that short-term dexamethasone treatment did not impair salivary gland function, whereas long-term dexamethasone treatment diminished store-operated Ca^(2+) entry, resulting in hyposalivation in mouse submandibular glands.

Effects of Beverage Ingredients on Salivary Fluid Secretion with an <i>ex Vivo</i>Submandibular Gland Perfusion System: Tannic Acid as a Key Component for the Inhibition of Saliva Secretion

Tannic acid (TA) and TA containing beverage have been proved to inhibit Ca2+-activated Cl- channel located apical membrane of the secretory cells. However, their effect on salivary fluid secretion is not well investigated. We used mouse ex Vivo submandibular gland perfusion technique to identify the general effect of TA and related beverage samples on muscarinic agonist carbachol induced fluid secretion. Green tea inhibited fluid secretion by 64% from the control, where oolong tea was by 53%, and red wine by 43% which was linked with their TA concentration. On the other hand, though TA was contained at 4.7 μM in white wine sample and 33 μM in coffee extract, no adverse effect was observed. In addition, coffee induced salivation in the absence of carbachol. TA had a negative effect on fluid secretion with a concentration dependent manner. The effects of TA on carbachol induced calcium increase showed identical as fluid secretion, which was initially no effect, and then gradually decreased over the time. These results demonstrate that TA directly inhibits the salivary fluid secretion and it affects not only Ca2+-activated Cl- channel but also intracellular Ca2+ increasing mechanisms.

Thermal influence of saliva secretion <i>ex vivo</i>in the mouse submandibular gland

The physiological and pharmacological responses of an ex vivo mouse submandibular gland were used to study fluid secretion and cell signaling in response to muscarinic stimulation at increasing temperatures. Saliva production at 37°C was 5.5-fold that at 25°C with pilocarpine stimulation and 9.8-fold that at 25°C with cevimeline stimulation. Both of these muscarinic agonists are used clinically. With the experimental agonist carbachol (CCh), saliva secretion was increased with an increase in temperature, but the CCh concentration producing the peak flow was the same in both dose-response curves, suggesting that the muscarinic receptor itself is not responsible for the temperature dependence. Purinergic agonists also induced temperature-dependent saliva production ex vivo. The calcium ionophore A23187 failed to have a significant effect on saliva production. The CCh-induced increase in intracellular Ca2+ also upregulated the initial increase and sustained the plateau phase of saliva flow. Thus, muscarinic receptor stimulation of saliva production is temperature sensitive due to an increase in intracellular Ca2+.

Stress Distribution in Maxillary Central Incisors without Ferrules: A Finite Element Analysis of Post and Core Systems

Purpose: The purpose of this study was to identify optimal post and core materials for central incisors without ferrules using three-dimensional finite element analysis and three-point bending tests. Methods: Stress analyses were performed with six models: cast metal post and core (MP), composite resin core alone, straight fiber-reinforced post-composite resin core (FSR), tapered fiber-reinforced post-composite resin core, straight titanium post-composite resin core (TSR), and tapered titanium post-composite resin core (TTR). A 100-N load was applied to the lingual surface at a 45° angle to the long axis of the tooth. Maximum von Mises stress distributions were calculated with finite element analysis software. Five samples each of composite resin, straight fiber-reinforced post, straight titanium post, straight fiber-reinforced post and composite resin, and straight titanium post and composite resin were subjected to three-point bending tests, followed by analysis of variance and Tukey’s multiple comparison test. Results: Stress distribution was optimal on TTR. Maximum von Mises stress on the cervical side of the post was greatest in TSR (693 MPa) and TTR (556 MPa). Maximum stress on the apical side of the post was greatest in MP (110 MPa). Maximum stress in surrounding dentin was lowest in MP (203 MPa) and TTR (250 MPa). Gap distance was smallest in MP (0.09 mm) and largest in FSR (0.26 mm). Mean maximum three-point bending force was lowest in composite resin (26.9 N/mm) and highest in titanium post and composite resin (97.1 N/mm). Titanium post bending strength was consistently greater than that of the fiber-reinforced post (p < 0.01). Conclusion: These results revealed optimal stress distribution and high bending strength with the tapered titanium post and resin combination, suggesting that this combination can most effectively prevent root or post fracture in an anterior tooth without a ferrule.