Clinical practice guideline for Sjögren's syndrome 2017.

OBJECTIVES: The objective of this study is to develop clinical practice guideline (CPG) for Sjögren's syndrome (SS) based on recently available clinical and therapeutic evidences. METHODS: The CPG committee for SS was organized by the Research Team for Autoimmune Diseases, Research Program for Intractable Disease of the Ministry of Health, Labor and Welfare (MHLW), Japan. The committee completed a systematic review of evidences for several clinical questions and developed CPG for SS 2017 according to the procedure proposed by the Medical Information Network Distribution Service (Minds). The recommendations and their strength were checked by the modified Delphi method. The CPG for SS 2017 has been officially approved by both Japan College of Rheumatology and the Japanese Society for SS. RESULTS: The CPG committee set 38 clinical questions for clinical symptoms, signs, treatment, and management of SS in pediatric, adult and pregnant patients, using the PICO (P: patients, problem, population, I: interventions, C: comparisons, controls, comparators, O: outcomes) format. A summary of evidence, development of recommendation, recommendation, and strength for these 38 clinical questions are presented in the CPG. CONCLUSION: The CPG for SS 2017 should contribute to improvement and standardization of diagnosis and treatment of SS.

Resveratrol improves salivary dysfunction in a non-obese diabetic (NOD) mouse model of Sjögren's syndrome.

Resveratrol is a natural polyphenol produced by plants in response to environmental stress. This compound has been shown to have pharmacological effects against a wide range of diseases including neurological, hepatic, cardiovascular and autoimmune conditions. The non-obese diabetic (NOD) mouse, in which loss of lacrimal and salivary gland function occurs, has been studied as an animal model for Sjögren's syndrome. In this study, we confirmed that administration of resveratrol results in increased secretion of saliva in NOD mice. Although resveratrol enhanced Sirt1 activity, inflammatory cell infiltration was not affected. Moreover, expression of the anti-inflammatory cytokine IL-10 in salivary glands was enhanced in the resveratrol-administered group. Thus, we confirmed a novel therapeutic effect for resveratrol on salivary dysfunction in Sjögren's syndrome.

Therapeutic effects of isoflavones on impaired salivary secretion.

Dry mouth, which is characterized by decreased salivation, has a number of causes; the involvement of estrogen has been suggested as symptoms typically develop in middle-aged females. However, there is a lack of consensus regarding the treatment of this condition. Soy isoflavones, a subgroup of flavonoids, are abundantly found in the soy germ. They are thought to exert a number of effects by specifically binding to estrogen receptors due to their structural similarity to estrogen. Recently, soy isoflavones have been found to exert antioxidant effects, ameliorating disorders caused by reactive oxygen/free radicals. Based on these observations, the effects of soybean isoflavones on impaired salivary secretion were studied in patients with dry mouth. Soy isoflavone aglycones were administered at 25 mg per day to 15 subjects with an average age of 67.9 ± 8.0 years for 2 months, and salivary secretion was analyzed. The results showed a significant improvement based on the saliva flow rate and self-completed questionnaire, thus suggesting the usefulness of isoflavones in improving the symptoms of salivary gland hypofunction.

Rapid multiplex real-time PCR assay using a portable device for the detection of oral pathogens.

Colonization by several oral pathogens and the onset of oral diseases, such as dental caries and periodontal diseases, are closely related. Therefore, the analysis of pathogens in oral specimens would be helpful for the risk assessment of oral diseases. We developed a rapid multiplex real-time polymerase chain reaction (PCR) method using a portable device and newly designed probe/primer sets to detect the oral pathogens Streptococcus mutans, Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia. The theoretical minimum detectable cell numbers of S. mutans, P. gingivalis, T. denticola, and T. forsythia were 1, 1, 4, and 3, respectively. The multiplex real-time PCR system simultaneously detected the colonization of S. mutans and P. gingivalis in human saliva. These results suggest that the multiplex real-time PCR system may be useful for the risk assessment of oral diseases.

Study on the salivation effect of encapsulated food products containing Sichuan pepper oil.

Sichuan pepper is a plant belonging to the genus Zanthoxylum and family rue. To evaluate whether Sichuan pepper oil boosts saliva secretion using an encapsulated food product containing the oil in subjects presenting with mouth dryness. We evaluated subjective symptoms that changed with a decrease in salivary secretion in the subjects by evaluating the number of Candida colonies and by conducting interviews. The study results demonstrated that salivary secretion increased by 39.4% ± 37.6% after single ingestion of the product, and an additional 8.7% ± 13.2% and 6.3% ± 31.2% following continuous ingestion over 2 and 4 weeks, respectively. These findings suggested that the product rapidly promotes and maintains salivation. Regarding the proliferation of Candida colonies in subjects with mouth dryness, a negative correlation was observed between Candida colony number and salivary secretion quantity. Additionally, interviews revealed that subjective symptoms, such as mouth dryness, discomfort and pain in the mouth, difficulty swallowing the saliva, and feeling of stickiness in the mouth, improved shortly after single ingestion of the product, and mouth dryness was reduced by continuous consumption of the product. These findings indicated that the product studied promotes rapid salivary secretion, is effective in reducing the number of oral Candida colonies, and improves subjective symptoms such as mouth dryness.

Effect of gummy candy containing ubiquinol on secretion of saliva: A randomized, double-blind, placebo-controlled parallel-group comparative study and an in vitro study.

A randomized, double-blind, placebo-controlled, parallel-group comparative clinical study was conducted to examine the effects of ubiquinol (the reduced form of Coenzyme Q10) on secretion of saliva. This interventional study enrolled 40 subjects aged 65 years or younger who were healthy, but noted slight dryness of the mouth. Subjects were randomized with stratification according to gender and age to ingestion of gummy candy containing 50 mg of ubiquinol or placebo twice daily for 8 weeks. At the end of study, along with a significant increase of the CoQ10 level in saliva (p = 0.025*, d = 0.65), there was a significant increase of the saliva flow rate (p = 0.048*, d = 0.66) in the ubiquinol candy group (n = 18; 47.4±6.2 years; 6 men and 12 women) compared to the placebo group (n = 20; 52.2±7.7 years; 4 men and 16 women). The strength of the stomatognathic muscles was not significantly enhanced by ingestion of ubiquinol candy. Compared with baseline, significant improvement of the following four questionnaire items was observed in the ubiquinol group at the end of the study: feeling tired (p = 0.00506, d = -0.726), dryness of the mouth (p = 0.04799, d = -0.648), prone to catching a cold (p = 0.00577, d = -0.963), and diarrhea (p = 0.0166, d = -0.855). There were no serious adverse events. An in vitro study revealed that ubiquinol stimulated a significant and concentration-dependent increase of ATP production by a cell line derived from human salivary gland epithelial cells (p<0.05), while 1 nM ubiquinol significantly suppressed (p = 0.028) generation of malondialdehyde by cells exposed to FeSO4-induced oxidative stress. These findings suggest that ubiquinol increases secretion of saliva by suppressing oxidative stress in the salivary glands and by promoting ATP production. Trial Registration: UMIN-CTR UMIN000024406.

[ Anti-aging dental medicine and calcium metabolism].

Anti-aging medicine is defined as the medicine which makes maintaining health and youth possible while growing older. Saliva has growth factors and antibacterial agents important for biological homeostasis, and various other substances vital for maintaining general health. The dentistry field also has a deep involvement in dental caries and bone formation (alveolar bone) . This article will discuss recent advances of anti-aging dental medicine including calcium metabolism.

Evaluation of the effects of quercetin on damaged salivary secretion.

With the aim of discovering an effective method to treat dry mouth, we analyzed the effects of quercetin on salivary secretion and its mechanism of action. We created a mouse model with impaired salivary secretion by exposure to radiation and found that impaired secretion is suppressed by quercetin intake. Moreover, secretion levels were enhanced in quercetin-fed normal mice. To elucidate the mechanisms of these effects on salivary secretion, we conducted an analysis using mouse submandibular gland tissues, a human salivary gland epithelial cell line (HSY), and mouse aortic endothelial cells (MAECs). The results showed that quercetin augments aquaporin 5 (AQP5) expression and calcium uptake, and suppresses oxidative stress and inflammatory responses induced by radiation exposure, suggesting that quercetin intake may be an effective method to treat impaired salivary secretion.

Possible benefits of singing to the mental and physical condition of the elderly.

BACKGROUND: The evaluation and management of stress are important for the prevention of both depression and cardiovascular disease. In addition, the maintenance of the oral condition of the elderly is essential to enable them to stay healthy, especially to prevent aspiration pneumonia and improve mental health in an aging society. Therefore, we examined the efficacy of singing on the oral condition, mental health status, and immunity of the elderly to determine if singing could contribute to the improvement of their physical condition. METHODS: Forty-four subjects (10 men, 34 women), aged 60 years or older, participated in this study. The efficacy of singing on mental health status and immunocompetence was examined by swallowing function, oral condition, blood, and saliva tests, as well as through questionnaires taken before and after singing. RESULTS: The results showed that the amount of saliva increased and the level of cortisol, a salivary stress marker, decreased after singing. The Visual Analog Scale (VAS) scores for feeling refreshed, comfortable, pleasurable, light-hearted, relieved, and relaxed; the tension and confusion subscale score; and the total mood disturbance (TMD) score of the Profile of Mood States (POMS) all showed improvements. Furthermore, the same tendencies were shown regardless of whether or not the subjects liked singing. CONCLUSIONS: Our results suggest that singing can be effective in improving the mental health and oral condition of the elderly.

Effects of coenzyme Q10 on salivary secretion.

OBJECTIVES: Dry mouth is a condition associated with reduced salivary secretion and is thought to be related to aging. This study was conducted to test whether reduced (ubiquinol) or oxidized (ubiquinone) forms of CoQ10 affect salivary secretion and salivary CoQ10 content before and after treatment. DESIGN AND METHODS: Sixty-six patients were given either ubiquinol or ubiquinone orally at a dosage of 100 mg/day, or a placebo for 1 month, and salivary secretion and salivary CoQ10 content were analyzed before and after treatment. RESULTS: Both parameters were significantly improved following treatment with either form of CoQ10, suggesting the effectiveness of CoQ10 in attenuating dry mouth symptoms. CONCLUSION: CoQ10 was locally detected in salivary glands, suggesting that orally administered CoQ10 was transported to the salivary glands via the blood stream and exerted its activity, improving salivary secretion.

Evaluation of therapeutic effects of astaxanthin on impairments in salivary secretion.

The involvement of reactive oxygen species (ROS) in the pathophysiology of Sjögren's syndrome (SS), an autoimmune disorder, and irradiation-induced impairments in salivary secretion has been reported. Meanwhile, the strong antioxidant astaxanthin (Ast) has been suggested to have therapeutic effects on various diseases. In the present study, we examined the ROS scavenging capacity of Ast using a human salivary gland epithelial cell line (HSY) and investigated the effects of Ast on salivary secretion in a mouse model of irradiation-induced salivary gland dysfunction. Furthermore, we performed a clinical study of Ast in six SS patients and six normal individuals, quantifying the volume of saliva secretion and the level of oxidative stress markers in the saliva. Ast partially suppressed hydrogen peroxide-induced ROS in HSY cells. The mouse model demonstrated that the pre-administration of Ast resulted in the suppression of irradiation-induced hyposalivation. Furthermore, the administration of Ast appeared to increase salivary output in both the SS and normal groups. The level of oxidative stress marker, hexanoyl-lysine, in the saliva was reduced after Ast intake. These results suggest that Ast might act as an ROS scavenger, providing benefits to SS patients with impaired salivary secretion.

Possible involvement of oxidative stress in salivary gland of patients with Sjogren's syndrome.

OBJECTIVE: To determine the involvement of oxidative stress in the salivary gland of patients with Sjogren's syndrome (SS). METHODS: Oxidative damage to the gland was measured by 8-hydroxy-2'-deoxyguanosine (8-OHdG) and hexanoyl-lysine (HEL) using the SS saliva. In addition, lactate dehydrogenase (LDH) and mitochondrial glutamic-oxaloacetic transaminase (m-GOT), both general markers for cell damage, were also analyzed. RESULTS: Increased levels of 8-OHdG and HEL were found in the saliva of SS patients, but not in that of patients with other salivary gland dysfunction or of healthy individuals. Levels of LDH and m-GOT were significantly correlated with 8-OHdG and HEL levels, respectively. Furthermore, the increased levels of 8-OHdG and HEL were also correlated in the SS saliva. CONCLUSION: These findings suggested the involvement of oxidative stress in glandular tissue destruction in SS. It was indicated that the detection of 8-OHdG and HEL in the saliva may become a useful tool for the diagnosis of SS.