Hyposecretion occurs in most patients early after submandibular gland autotransplantation for severe keratoconjunctivitis sicca. Endogenous transient receptor potential vanilloid subtype 1 (TRPV1) has been recently demonstrated in rabbit submandibular glands, and activation of TRPV1 by capsaicin increases secretion in isolated glands, but the TRPV1-mediated secretory mechanism remains to be elucidated. The purpose of this study was to verify whether activation of TRPV1 by capsaicin could improve the secretion of transplanted gland and its underlying mechanism. The salivary flow of the transplanted glands was significantly decreased, and the mRNA and protein levels of TRPV1 and aquaporin 5 (AQP5) were downregulated in the transplanted glands. Topical capsaicin cream increased secretion and upregulated levels of TRPV1 and AQP5 in transplanted glands. Moreover, in cultured submandibular gland cells, capsaicin increased the mRNA expression of AQP5 and led to redistribution of AQP5 from the cytoplasm to the plasma membrane via TRPV1 activation. Capsaicin enhanced the phosphorylation of extracellular signal-regulated kinase (ERK). Preincubation of cells with PD98059, an inhibitor of ERK kinase, suppressed the capsaicin-induced mRNA expression of AQP5. In summary, the capsaicin-induced secretory mechanism involved activation of TRPV1 and upregulation of AQP5 in an ERK-dependent manner and promoted the redistribution of AQP5 in submandibular gland cells. Activation of TRPV1 may provide a new therapeutic strategy to improve submandibular gland hypofunction.

Multipacting (MP) in higher-order-mode (HOM) couplers of the International Linear Collider (ILC) baseline cavity and the Continuous Electron Beam Accelerator Facility (CEBAF) 12 GeV upgrade cavity is studied by using the ACE3P suites, developed by the Advanced Computations Department at SLAC. For the ILC cavity HOM coupler, the simulation results show that resonant trajectories exist in three zones, corresponding to an accelerating gradient range of 0.6-1.6 MV=m, 21-34 MV=m, 32-35 MV=m and >40 MV=m, respectively. For the CEBAF 12 GeV upgrade cavity HOM coupler, resonant trajectories exist in one zone, corresponding to an accelerating gradient range of 6-13 MV=m. Potential implications of these MP barriers are discussed in the context of future high-energy pulsed as well as medium-energy continuous wave accelerators based on superconducting radio frequency cavities. Frequency scaling of MP's predicted in HOM couplers of the ILC, CEBAF upgrade, Spallation Neutron Source (SNS), and Free-Electron Laser in Hamburg (FLASH) third harmonic cavity is given and found to be in good agreement with the analytical result based on the parallel plate model.