Analysis of medication-induced xerostomia in elderly Japanese patients.

OBJECTIVES: To determine the general condition of elderly xerostomia patients, we collected their background and medication data in order to potentially treat their xerostomia. It is critical to identify the drugs causing xerostomia in elderly patients. A total of 521 patients who were examined at the Xerostomia Clinic of Osaka University Dental Hospital were included in the study. We obtained patients' data on age, sex, number of primary illnesses, Saxon test scores, oral moisture test, subjective symptoms, and drug types from their clinical records. RESULTS: The mean age of the patients was 65.2 ± 13.3 years. Although all patients exhibited xerostomia symptoms, there were a lot of patients without hyposalivation. With respect to medication, each elderly xerostomia patient took an average of 6.8 ± 4.4 medicines. A total of 26.1% of patients in their 70 s took more than ten number of drugs. In addition, the number of frequently used medication medicine was different between elderly and young patients. Most of the medicines had xerostomia as a side effect in medical package inserts. Moreover, the quantity of salivation significantly decreased in patients who took more than seven drugs in comparison with the patients who did not take medicine. CONCLUSIONS: As patients age, the number of medications they take tends to increase, subsequently increasing their risk of xerostomia. For the health of the patients, it is critical that an accurate diagnosis is made. CLINICAL RELEVANCE: To establish therapeutic strategies for treatment of xerostomia, this study provides new and important information that will help in the development of xerostomia medical treatment.

ΔNp63 is upregulated during salivary gland regeneration following duct ligation and irradiation in mice.

The transcription factor p63, a component of the p53 family, has important functions in development, homeostasis, and regeneration of epithelial tissues. However, the role of p63 in the regeneration of exocrine glands, including the salivary glands (SGs), has not been fully investigated. We investigated p63 expression in SG regeneration induced by duct ligation and irradiation. The expression of ΔNp63, a p63 isoform, increased and was colocalized with keratin 5 positive cells were myoepithelial cells. Furthermore, ΔNp63 expression was regulated by FGF7 stimulation via p38 MAPK phosphorylation and affected SG morphogenesis. These results suggest that ΔNp63 is essential for SG regeneration and may be a new target for regenerative treatment.

Role of the mTOR signalling pathway in salivary gland development.

Development of the salivary gland is characterized by extensive branching morphogenesis. Although various molecules have been implicated in salivary gland development, the role of the mammalian target of rapamycin (mTOR) signalling pathway, including both mTOR complexes 1 and 2 (mTORC1 and 2), in salivary gland development is unknown. Here, we examined protein expression levels related to the mTOR signalling pathway using an ex vivo submandibular salivary gland (SMG) organ culture. We showed that branching buds in the salivary glands were substantially decreased and phosphorylation of mTORC1 signalling pathway related proteins (mTOR, p70 ribosomal protein S6 kinase 1 and eukaryotic initiation factor 4E-binding protein 1) was inhibited by rapamycin (an mTOR inhibitor). In addition, AKT, which is an upstream protein kinase of mTORC1 and is downstream of mTORC2, is inhibited by LY294002 (a phosphatidylinositol 3-kinase inhibitor), but not by rapamycin. Moreover, rapamycin-treated ICR neonatal mice exhibited a reduction in both body weight and salivary glands compared with vehicle-treated neonatal mice. The present data indicate that the mTOR signalling pathway, including both mTORC1 and mTORC2, plays a critical role in salivary gland development both in ex vivo SMG organ culture and ICR neonatal mice in vivo.

The efficacy of nasal airway stent (Nastent) on obstructive sleep apnoea and prediction of treatment outcomes.

BACKGROUND: Obstructive sleep apnoea (OSA) is characterised by recurrent episodes of partial or complete upper airway collapse during sleep and is highly prevalent in the general population. The nasopharyngeal airway stent (Nastent) is a specifically designed, preformed silicone tube that intends to maintain the upper airway patency during sleep and reduce snoring and sleep apnoea. OBJECTIVE(S): The purpose of this study was to determine the efficacy of Nastent treatment and examine predictors for Nastent treatment outcomes in patients with OSA. METHODS: Consecutive thirty patients were enrolled in this study. Cephalometric radiographs were obtained to analyse the pharyngeal and craniofacial morphology. Before and after Nastent treatment, we evaluated OSA using a portable sleep study. RESULTS: Twenty-nine subjects completed this study. There were significant decreases in the respiratory event index (REI) (22.4 ± 14.1 to 15.7 ± 10.4, P < 0.01) and a significant increase in the lowest SpO2 (81.9 ± 7.5 to 86.6 ± 4.8, P < 0.01) by Nastent treatment. Subjects were divided into responders and non-responders based on reduction in REI of >50% compared with baseline REI. We evaluated the ratio of inferior airway width and middle airway width (IAW/MAW) on cephalograms as the index of the narrowest airway site. The IAW/MAW was significantly higher in responders than in non-responders (1.4 ± 0.9 vs 0.9 ± 0.4, P < 0.01) and predicted treatment responders with high accuracy (sensitivity: 90.9%, specificity: 88.9%, when IAW/MAW was set at 1.10). CONCLUSIONS: The Nastent device improved OSA, and a narrower velopharynx than hypopharynx predicted treatment response with a good sensitivity and specificity.

Benefits of long-term pilocarpine due to increased muscarinic acetylcholine receptor 3 in salivary glands.

Hypofunction of the salivary gland causes several life-disrupting side effects such as dental caries, oral candidiasis, loss of taste, and swallowing disorders. No satisfactory therapy has been established to treat salivary hypofunction. Pilocarpine represents a potential treatment for dry mouth due to Sjögren's syndrome (SS). Although subjective improvement was consistently observed with pilocarpine therapy, the mechanism was unclear. In this study, we investigated the mechanism of recovery in salivation following treatment with pilocarpine. We first examined the effectiveness of pilocarpine in SS patients as quantified by the Saxon test and the visual analogue scale average. We found that salivation ability and subjective symptoms improved by continuous administration of pilocarpine. These results demonstrated that long-term medication for dry mouth patients was more effective. However, as the mechanism remained unclear, molecular biological mechanisms were analyzed based on the effects of continuous administration of pilocarpine using model mice. In the molecular biological analysis, continuous administration of pilocarpine was effective in both ICR and SS model mice. Gene and protein expression of muscarinic acetylcholine receptor 3 (M3R) increased in salivary glands following continuous administration of pilocarpine compared with single administration. Therefore, continuous administration of pilocarpine effectively induced M3R expression, thereby activating salivation.

Titration technique using endoscopy for an oral appliance treatment of obstructive sleep apnea.

The degree of mandibular protrusion for an oral appliance (OA) should be customized for each patient with obstructive sleep apnea (OSA). This article describes the mandibular titration technique for OAs to effectively treat OSA by using endoscopy to evaluate the change in the airway at the velopharynx. This technique may minimize the degree of mandible protrusion and contribute to both the efficacy of and compliance with OA therapy.

Identification of the protective mechanisms of Lactoferrin in the irradiated salivary gland.

Radiotherapy is commonly used in patients with head and neck cancer, and usually results in irreversible salivary glands damage and hypofunction. It is therefore important to manage such irradiation to prevent damage to the salivary glands. A previous study showed that Lactoferrin (LF) has a radioprotective effect, but the mechanism was not determined in salivary glands. In the present study, we investigated the detailed radioprotective effect of LF using both ex vivo submandibular salivary gland organ culture and ICR male mice in vivo. We found that LF had effects on both cell proliferation and CyclinD1-mediated cell-cycle progression which were regulated via the ERK1/2 and AKT signal transduction pathways. In addition, LF affected acinar cell structure and function after irradiation. These findings suggest that LF may be a useful agent to prevent irradiation effects in salivary glands.