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ASP8302 is an orally administered positive allosteric modulator of the muscarinic M3 receptor. Two Phase 1 studies were conducted, a first‐in‐human study in Europe and a Japanese phase 1 study. Both were randomized, participant‐ and investigator‐blinded, placebo‐controlled, single and multiple ascending oral doses, parallel group, clinical studies in healthy volunteers. Both studies evaluated safety and pharmacokinetics and also included salivary secretion and pupil diameter as pharmacodynamic assessments. There were no deaths, serious adverse events, or treatment‐emergent adverse events reported leading to study discontinuation. There were no clinically relevant findings in any of the laboratory, vital signs, electrocardiogram assessments, or photosensitivity testing following multiple administration of up to 150 mg or up to 140 mg once daily for 14 days in the European first‐in‐human and Japanese Phase 1 study, respectively. The pharmacokinetics of ASP8302 were approximately linear over the dose range studied. There was no evidence of drug accumulation upon repeated dosing. In both studies, ASP8302 showed a dose‐dependent pharmacodynamic effect on saliva production at doses from 100 mg onward, which was maintained during repeated dosing. No effect was observed on pupil diameter. These data supported progression of ASP8302 into Phase 2 clinical trials for further clinical development. [ABSTRACT FROM AUTHOR]

Background: Although low-level laser therapy (LLLT) is a widely used noninvasive treatment because of photobiomodulation effects, its application for xerostomia remained uncertain. Tight junctions (TJs), mainly composed of claudins, occludin, and ZO family members, are crucial structures that determine material transport through paracellular pathway in salivary gland epithelial cells. This work aimed to investigate whether LLLT affected salivary secretion through epithelial TJs. Methods: Transepithelial electrical resistance (TER) measurement and paracellular permeability assay were applied to evaluate paracellular permeability in submandibular gland (SMG)-C6 cells after irradiation with 540 nm green light. Immunofluorescence and western blot were used to detect the expression of TJ proteins. Quantitative phosphoproteomics were performed to explore possible intracellular signals. Results: We found that irradiation with 540 nm green light significantly decreased TER values while increased paracellular transport in SMG-C6 cells. 540 nm green light-induced redistribution of claudin-1, -3, and -4, but not occludin or ZO-1. Moreover, above phenomena were abolished by preincubation with capsazepine, an antagonist of transient receptor potential vanilloid subtype 1. Notably, irradiation with 540 nm green light on the skin covering the whole submandibular gland regions promoted salivary secretion and attenuated lymphocytic infiltration in 21-week-old non-obese diabetic mice (n = 5 per group), a xerostomia animal model for Sjögren's syndrome. Through in-depth bioinformatics analysis and expression verification, ERK1/2 and EphA2 served as potential canonical and noncanonical signals underlying 540 nm green light. Conclusions: Our findings uncovered the novel therapeutic effects of 540 nm green light on xerostomia through regulation on the expression and distribution of TJs. [ABSTRACT FROM AUTHOR]

This in vivo mouse model study was conducted to investigate the temporal alteration of the function of CD36 in salivary secretion. CD36 was highly expressed in the parotid gland of BALB/c mice. No significant variations were shown in the CD36 levels in the 8-, 48-, and 72-week-old animals. However, pilocarpine-induced salivary secretion was reduced in an age-dependent manner, showing a significantly low level at the age of 72 weeks. Pilocarpine-induced salivary secretion was significantly reduced by pretreatment with a CD36 inhibitor at 8 and 48 weeks, but not at 72 weeks. In senescence-accelerated mice (SAM), the pilocarpine-induced salivary secretion was significantly reduced at the age of 56 weeks, and a significantly lower amount of CD36 was demonstrated in the parotid gland, compared with the control. These results suggest that the involvement of parotid CD36 in mouse salivary secretion is altered with age. [ABSTRACT FROM AUTHOR]

Saliva is a liquid in the oral cavity that has an important role. Decreased secretion and increased salivary viscosity occur physiologically as a result of changes and decreased function of the salivary glands in the aging process. Changes in salivary secretion patterns and viscosity in the elderly in various age groups are thought to be related to the occurrence of xerostomia in the elderly. This research was a descriptive analytic research. The research subjects were elderly patients at the Oral Medicine department. The research subjects were divided into three age groups, namely 45-59 years, 60-69 years and over 70 years. Respondent's saliva was collected using the drooling method. Saliva was collected every minute for 5 minutes to measure salivary secretion.The salivary viscosity is measured by Ostwald viscometer, and anamnesis, intra oral examination for xerostomia. Data analysis used the One Way Anova test and was continued with Duncan's Post Hoc Test to determine the differences between each age group and analyzed with a mean plot to find the average between groups Based on the results of the One Way ANOVA test with P<0.05, there were significant differences in salivary secretion (P=0.004) and viscosity (P=0.002). Salivary secretion and viscosity are related to complaints of xerostomia in the elderly. The highest decrease in saliva secretion occurred between the ages of 60-69 years, accompanied by 69% of symptoms of xerostomia. The highest increase in viscosity occurred at age ≥70 accompanied by 100% xerostomia symptoms. [ABSTRACT FROM AUTHOR]

Sjogren's syndrome (SS) is an autoimmune disease characterized by dysfunction of exocrine glands, such as salivary glands. However, the molecular mechanism of salivary secretion dysfunction in SS is still unclear. Given the significance of glutathione peroxidase 4 (GPX4) in cellular redox homeostasis, we hypothesized that dysregulation of GPX4 may play a pivotal role in the pathogenesis of salivary secretion dysfunction observed in SS. The salivary gland of SS patients and the SS mouse model exhibited reduced expression of the ferroptosis inhibitor GPX4 and the important protein aquaporin 5 (AQP5), which is involved in salivary secretion. GPX4 overexpression upregulated and GPX4 knockdown downregulated AQP5 expression in salivary gland epithelial cells (SGECs) and salivary secretion. Bioinformatics analysis of GSE databases from SS patients' salivary glands revealed STAT4 as a key intermediary regulator between GPX4 and AQP5. A higher level of nuclear pSTAT4 was observed in the salivary gland of the SS mouse model. GPX4 overexpression inhibited and GPX4 knockdown promoted STAT4 phosphorylation and nuclear translocation in SGECs. CHIP assay confirmed the binding of pSTAT4 within the promoter of AQP5 inhibiting AQP5 transcription. GPX4 downregulation accumulates intracellular lipid ROS in SGECs. Lipid ROS inhibitor ferrostatin-1 treatment during in vitro and in vivo studies confirmed that lipid ROS activates STAT4 phosphorylation and nuclear translocation in SGECs. In summary, the downregulated GPX4 in SGECs contributes to salivary secretion dysfunction in SS via the lipid ROS/pSTAT4/AQP5 axis. This study unraveled novel targets to revitalize the salivary secretion function in SS patients. Among patients with Sjogren's syndrome, inflammation stimulates the system Xc− - GSH axis in salivary gland epithelial cells, leading to the subsequent downregulation of GPX4. Consequently, the diminished capacity of GPX4 to clear lipid reactive oxygen species (ROS) from cells results in cell death and subsequent dysfunction in salivary secretion. Concurrently, lipid ROS induces STAT4 phosphorylation, facilitating its nuclear translocation and binding to the AQP5 promoter region. Ultimately, this cascade leads to the inhibition of AQP5 transcription, culminating in impaired salivary secretion. [Display omitted] • Downregulated GPX4 and salivary gland epithelial cells (SGECs) dysfunction are observed in Sjogren's syndrome (SS). • Downregulated GPX4-induced lipid ROS promotes STAT4 phosphorylation (pSTAT4) in SGECs. • pSTAT4 binds to the promoter region of AQP5 inhibiting AQP5 expression and salivary secretion by SGECs. • Downregulated GPX4 in SS SGECs contributes not only to ferroptosis but also to hyposalivation. [ABSTRACT FROM AUTHOR]

In salivary acinar cells, cholinergic stimulation induces elevations of cytosolic [Ca2+]i to activate the apical exit of Cl− through TMEM16A Cl− channels, which acts as a driving force for fluid secretion. To sustain the Cl− secretion, [Cl−]i must be maintained to levels that are greater than the electrochemical equilibrium mainly by Na+-K+-2Cl− cotransporter-mediated Cl− entry in basolateral membrane. Glucose transporters carry glucose into the cytoplasm, enabling the cells to produce ATP to maintain Cl− and fluid secretion. Sodium–glucose cotransporter-1 is a glucose transporter highly expressed in acinar cells. The salivary flow is suppressed by the sodium–glucose cotransporter-1 inhibitor phlorizin. However, it remains elusive how sodium–glucose cotransporter-1 contributes to maintaining salivary fluid secretion. To examine if sodium–glucose cotransporter-1 activity is required for sustaining Cl− secretion to drive fluid secretion, we analyzed the Cl− currents activated by the cholinergic agonist, carbachol, in submandibular acinar cells while comparing the effect of phlorizin on the currents between the whole-cell patch and the gramicidin-perforated patch configurations. Phlorizin suppressed carbachol-induced oscillatory Cl− currents by reducing the Cl− efflux dependent on the Na+-K+-2Cl− cotransporter-mediated Cl− entry in addition to affecting TMEM16A activity. Our results suggest that the sodium–glucose cotransporter-1 activity is necessary for maintaining the oscillatory Cl− secretion supported by the Na+-K+-2Cl− cotransporter activity in real time to drive fluid secretion. The concerted effort of sodium–glucose cotransporter-1, Na+-K+-2Cl− cotransporter, and apically located Cl− channels might underlie the efficient driving of Cl− secretion in different secretory epithelia from a variety of animal species. [ABSTRACT FROM AUTHOR]

Haia Mohammed Kamihan Alenazi, Mohammad Abdul Baseer, Osamah Mohammed AlMugeiren, Navin Anand Ingle Preventive Dentistry Department, College of Medicine and Dentistry, Riyadh Elm University, Riyadh, Saudi ArabiaCorrespondence: Mohammad Abdul Baseer, Preventive Dentistry Department, College of Medicine and Dentistry, Riyadh Elm University, P.Box 84891, Riyadh, 11681, Saudi Arabia, Email ma_baseer@riyadh.edu.saObjective: This study aimed to assess and compare the salivary secretion, pH, and buffer capacity between COVID-19 vaccinated and unvaccinated child patients visiting the clinics of private university dental hospitals in Riyadh, Saudi Arabia.Methods: This is the first comparative assessment of salivary parameters between unvaccinated and COVID-19-vaccinated child patients. The study sample comprised COVID-19 unvaccinated (n = 66) and vaccinated (n = 66) pediatric dental patients aged 4– 12 years seeking dental care in clinics of private university hospitals. Paraffin-stimulated saliva was collected from unvaccinated and vaccinated study participants, and the amount of saliva secreted per minute was noted. Salivary pH and buffering capacity (by 5 mmol Hydrochloric acid titration) were measured using a benchtop digital pH meter. The data obtained were compared between unvaccinated and vaccinated participants using an independent t-test.Results: The results showed a significantly higher salivary secretion rate in unvaccinated than vaccinated study participants (0.83 ± 0.24 mL/min vs 0.67 ± 0.24 mL/min, p = 0.001). Similarly, unvaccinated subjects compared to vaccinated subjects exhibited a significantly higher pH (7.33 ± 0.39 vs 7.04 ± 0.46, p < 0.001) and buffering capacity (6.31 ± 1.55 vs 5.40 ± 1.22, p < 0.001). Moreover, unvaccinated females demonstrated a significantly higher salivary secretion (0.87 ± 0.23 vs 0.71 ± 0.25, t = 2.627, p = 0.011) and buffering capacity 6.19 ± 1.52 vs 5.34 ± 1.25, t = 2.404, p = 0.019) than vaccinated females. Similarly, unvaccinated male exhibited significantly higher salivary secretion (0.80 ± 0.25 vs 0.64 ± 0.23, t = 2.670, p = 0.009), salivary pH (7.39 ± 0.45 vs 6.94 ± 0.41, t=4.309, p< 0.001) and buffering capacity (6.42 ± 1.60 vs 5.45 ± 1.21, t = 2.875, p = 0.005) than the vaccinated male subjects.Conclusion: The vaccinated subjects showed a significantly lower mean salivary secretion, pH, and buffering capacity than unvaccinated participants. Hence, COVID-19 vaccination is likely to affect salivary parameters among pediatric patients.Keywords: COVID-19, vaccine, salivary secretion, pH, buffer, pediatric, patients

Abstract Background Sjogren’s syndrome (SS) is an autoimmune disorder characterized by the destruction of exocrine glands, resulting in dry mouth and eyes. Currently, there is no effective treatment for SS, and the mechanisms associated with inadequate salivary secretion are poorly understood. Methods In this study, we used NOD mice model to monitor changes in mice’s salivary secretion and water consumption. Tissue morphology of the submandibular glands was examined by H&E staining, and Immunohistochemical detected the expression of AQP5 (an essential protein in salivary secretion). Global gene expression profiling was performed on submandibular gland tissue of extracted NOD mice model using RNA-seq. Subsequently, a series of bioinformatics analyses of transcriptome sequencing was performed, including differentially expressed genes (DEGs) identification, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, PPI network construction, hub gene identification, and the validity of diagnostic indicators using the dataset GSE40611. Finally, IFN-γ was used to treat the cells, the submandibular gland tissue of NOD mice model was extracted, and RT-qPCR was applied to verify the expression of hub genes. Results We found that NOD mice model had reduced salivary secretion and increased water consumption. H&E staining suggests acinar destruction and basement membrane changes in glandular tissue. Immunohistochemistry detects a decrease in AQP5 immunostaining within acinar. In transcriptome sequencing, 42 overlapping DEGs were identified, and hub genes (REN, A2M, SNCA, KLK3, TTR, and AZGP1) were identified as initiating targets for insulin signaling. In addition, insulin signaling and cAMP signaling are potential pathways for regulating salivary secretion and constructing a regulatory relationship between target-cAMP signaling-salivary secretion. Conclusion The new potential targets and signal axes for regulating salivary secretion provide a strategy for SS therapy in a clinical setting.

Background: Sjogren's syndrome (SS) is an autoimmune disorder characterized by the destruction of exocrine glands, resulting in dry mouth and eyes. Currently, there is no effective treatment for SS, and the mechanisms associated with inadequate salivary secretion are poorly understood. Methods: In this study, we used NOD mice model to monitor changes in mice's salivary secretion and water consumption. Tissue morphology of the submandibular glands was examined by H&E staining, and Immunohistochemical detected the expression of AQP5 (an essential protein in salivary secretion). Global gene expression profiling was performed on submandibular gland tissue of extracted NOD mice model using RNA-seq. Subsequently, a series of bioinformatics analyses of transcriptome sequencing was performed, including differentially expressed genes (DEGs) identification, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, PPI network construction, hub gene identification, and the validity of diagnostic indicators using the dataset GSE40611. Finally, IFN-γ was used to treat the cells, the submandibular gland tissue of NOD mice model was extracted, and RT-qPCR was applied to verify the expression of hub genes. Results: We found that NOD mice model had reduced salivary secretion and increased water consumption. H&E staining suggests acinar destruction and basement membrane changes in glandular tissue. Immunohistochemistry detects a decrease in AQP5 immunostaining within acinar. In transcriptome sequencing, 42 overlapping DEGs were identified, and hub genes (REN, A2M, SNCA, KLK3, TTR, and AZGP1) were identified as initiating targets for insulin signaling. In addition, insulin signaling and cAMP signaling are potential pathways for regulating salivary secretion and constructing a regulatory relationship between target-cAMP signaling-salivary secretion. Conclusion: The new potential targets and signal axes for regulating salivary secretion provide a strategy for SS therapy in a clinical setting. [ABSTRACT FROM AUTHOR]

Intermittent fasting confers protections to various diseases including autoimmune disorders, but the specific effects of intermittent fasting on Sjögren's syndrome (SS) remains inconclusive. The present study was undertaken to determine the specific impact of alternate-day fasting (ADF) on newly established SS-like sialadenitis using non-obese diabetic (NOD) mice. Female NOD mice were deprived of food every other day from 10 to 13 weeks of age, the early stage of established SS, and then analyzed for the disease characteristics. Mice in the ADF group had higher salivary flow rate and attenuated submandibular gland (SMG) inflammation, compared to the control mice fed with standard chow ad libitum. The improvements were accompanied with a decrease in the total leukocytes, T and B lymphocytes and activated CD4 and CD8 T cells, and a down-regulation of pro-inflammatory cytokines IFN-γ and IL-17, chemokine receptor CXCR3 and its ligands CXCL9 and CXCL11 in the SMGs. ADF also led to elevated mRNA levels of water channel protein aquaporin 5 and tight junction protein claudin-1, two factors crucial for normal salivary secretion in the SMGs. In addition, ADF reduced the proportion of IFN-γ- and IL-17- expressing CD4 T cells and diminished mRNA levels of IFN-γ, TNF-α, and IL-17 in the total submandibular draining lymph node cells. Taken together, ADF is effective in ameliorating newly established SS-associated salivary gland exocrinopathy in NOD mice. [ABSTRACT FROM AUTHOR]

ASP8302 is an orally administered positive allosteric modulator of the muscarinic M 3 receptor. Two Phase 1 studies were conducted, a first-in-human study in Europe and a Japanese phase 1 study. Both were randomized, participant- and investigator-blinded, placebo-controlled, single and multiple ascending oral doses, parallel group, clinical studies in healthy volunteers. Both studies evaluated safety and pharmacokinetics and also included salivary secretion and pupil diameter as pharmacodynamic assessments. There were no deaths, serious adverse events, or treatment-emergent adverse events reported leading to study discontinuation. There were no clinically relevant findings in any of the laboratory, vital signs, electrocardiogram assessments, or photosensitivity testing following multiple administration of up to 150 mg or up to 140 mg once daily for 14 days in the European first-in-human and Japanese Phase 1 study, respectively. The pharmacokinetics of ASP8302 were approximately linear over the dose range studied. There was no evidence of drug accumulation upon repeated dosing. In both studies, ASP8302 showed a dose-dependent pharmacodynamic effect on saliva production at doses from 100 mg onward, which was maintained during repeated dosing. No effect was observed on pupil diameter. These data supported progression of ASP8302 into Phase 2 clinical trials for further clinical development., (© 2024 Astellas Pharma Inc, Clinical Pharmacology in Drug Development published by Wiley Periodicals LLC on behalf of American College of Clinical Pharmacology.)

Saliva plays multifunctional roles in oral cavity. Even though its importance for the maintenance of oral health has long been established, the role of saliva in food perception has attracted increasing attention in recent years. We encourage researchers to discover the peculiarity of this biological fluid and aim to combine the data concerning all aspects of the saliva influence on the sensory perception of food. This review presents saliva as a unique material, which modulates food perception due to constant presence of saliva in the mouth and thanks to its composition. Therefore, we highlight the salivary components that contribute to these effects. Moreover, this review is an attempt to structure the effects of saliva on perception of different food categories, where the mechanisms of salivary impact in perception of liquid, semi‐solid, and solid foods are revealed. Finally, we emphasize that the large inter‐individual variability in salivary composition and secretion appear to contribute to the fact that everyone experiences food in their own way. Therefore, the design of the sensory studies should consider the properties of volunteers' saliva and also carefully monitor the experimental conditions that affect salivary composition and flow rate. [ABSTRACT FROM AUTHOR]

Eating food is one of the most complicated behaviours in mammals, especially humans. The primary function of ghrelin is regulation of the appetite level and its stimulation. It is also responsible for the body’s energy balance and glucose homeostasis. Ghrelin has been shown to affect many brain structures, which confirms the presence of ghrelin receptors in the brain. Studies are also conducted to assess the possible role of ghrelin in anxiety states and in memory disorders and motor dysfunctions. Ghrelin has been found in saliva and salivary glands, teeth and gums, and in the taste buds of the tongue epithelium; it is also secreted by mucosal cells and gingival fibroblasts. The presence of ghrelin in developmental enamel, especially in odontoblasts and ameloblasts, may suggest its regulatory role in the development of teeth. Patients with chronic periodontitis have significantly higher concentrations of ghrelin in the peripheral blood serum, as compared to the control group. Ghrelin plays a special role in the proliferation of cancer cells and in the development of neoplastic metastases. The abundant presence of ghrelin receptors in cancer cells is considered an important target in the treatment of neoplasms. Ghrelin is a hormone whose multidirectional mechanism of action has not yet been fully understood. However, its ubiquitous occurrence in the human body and its very diverse participation in metabolic processes may prove to be a significant obstacle in achieving the expected clinical effect of ghrelin as an effective drug in selected disease units.

Pilocarpine‐induced salivary secretion could serve as a nontherapeutic target engagement biomarker in a clinical setting to test the activity of an M3 positive allosteric modulator (PAM). The potentiating effect on the reactivity of the M3 receptor to the agonistic effect of pilocarpine would support the mechanism of action of an M3 PAM in a variety of therapeutic areas. The aim of this study was to determine the optimal pilocarpine dose needed for evaluation of this potentiating effect. Therefore, the effects of pilocarpine on salivary secretion rate and its pharmacokinetics were explored at single doses of 2.5, 5, and 10 mg of pilocarpine or placebo. The study also explored the test‐retest variability of the pilocarpine‐induced effects on salivary secretion. Pilocarpine caused a reproducible, dose‐related increase in overall and maximum salivary secretion rate, in line with pilocarpine exposure. Oral doses of pilocarpine from 2.5 to 10 mg were safe and well tolerated, consistent with the published safety profile. These results support the use of pilocarpine in single‐dose pharmacological challenge studies. The recommended dose for evaluating M3 PAM activity would be between 2.5 and 5 mg, showing a small increase in salivary secretion rate with room for further increase due to PAM activation. [ABSTRACT FROM AUTHOR]

Background: Although low-level laser therapy (LLLT) is a widely used noninvasive treatment because of photobiomodulation effects, its application for xerostomia remained uncertain. Tight junctions (TJs), mainly composed of claudins, occludin, and ZO family members, are crucial structures that determine material transport through paracellular pathway in salivary gland epithelial cells. This work aimed to investigate whether LLLT affected salivary secretion through epithelial TJs. Methods: Transepithelial electrical resistance (TER) measurement and paracellular permeability assay were applied to evaluate paracellular permeability in submandibular gland (SMG)-C6 cells after irradiation with 540 nm green light. Immunofluorescence and western blot were used to detect the expression of TJ proteins. Quantitative phosphoproteomics were performed to explore possible intracellular signals. Results: We found that irradiation with 540 nm green light significantly decreased TER values while increased paracellular transport in SMG-C6 cells. 540 nm green light-induced redistribution of claudin-1, -3, and -4, but not occludin or ZO-1. Moreover, above phenomena were abolished by preincubation with capsazepine, an antagonist of transient receptor potential vanilloid subtype 1. Notably, irradiation with 540 nm green light on the skin covering the whole submandibular gland regions promoted salivary secretion and attenuated lymphocytic infiltration in 21-week-old non-obese diabetic mice ( n = 5 per group), a xerostomia animal model for Sjögren's syndrome. Through in-depth bioinformatics analysis and expression verification, ERK1/2 and EphA2 served as potential canonical and noncanonical signals underlying 540 nm green light. Conclusions: Our findings uncovered the novel therapeutic effects of 540 nm green light on xerostomia through regulation on the expression and distribution of TJs.

Type 2 diabetes mellitus (T2DM) is an increasing global public health concern, but its impact on the salivary proteome is still unclear. To evaluate the effect of glycemic levels in middle-aged and elderly individuals with T2DM on salivary proteomics, we compared the differences by liquid chromatography tandem mass spectrometry (LC–MS/MS). Unstimulated whole saliva samples from 8 T2DM patients with good glycemic control (G group, HbA1c

Carbonic acid tablets containing citric acid and sodium bicarbonate were designed to dissolve in aqueous solution, and release carbon dioxide (CO2). The effect of the carbonic acid tablets on salivary secretion was examined in humans. Healthy male volunteers participated in the whole salivary flow secretion (n = 6) and submandibular-sublingual (SMSL) gland and parotid gland salivary flow secretion (n = 12) studies. Placement of a carbonic acid tablet on the apex of the tongue increased the whole saliva volume. The carbonic acid tablets promoted SMSL salivary secretion, but had less effect on parotid salivary secretion. A citric acid tablet, an acidic tastant, promoted both SMSL and parotid salivary secretion. A tablet containing only sodium bicarbonate, a component of the carbonic acid tablet, had no effect on SMSL salivary secretion. In conclusion, a carbonic acid stimulus specifically enhances salivary secretion from SMSL glands via the formation of CO2.

Background/purpose: Although it has been reported that capsaicin ingestion has effects of protecting stomach mucosa and promoting energy consumption, physiological responses to oral stimulation with capsaicin has not been elucidated. Therefore, we investigated the effect of oral capsaicin stimulation on oral health and mental conditions by measuring changes in salivation, autonomic nervous activity and electroencephalogram (EEG). Materials and methods: Eighteen healthy adults participated in this study. The stimulus concentrations of capsaicin and five basic taste solutions were determined based on the measured threshold of each stimulus in each subject. The weight of secreted saliva and the changes in concentrations of salivary secretory immunoglobulin A (SIgA) induced by capsaicin and taste stimuli were measured. Salivary α-amylase activity and heart rate variability (HRV) were measured as indicators of autonomic nervous activity. From EEG, psychological condition was analyzed by measuring the powers of theta, alpha, and beta bands. Results: The salivary secretion rate was significantly increased by stimulation with capsaicin, NaCl, and citric acid compared with deionized water, and capsaicin demonstrated the most potent effect among tested stimuli. The secreted amount of SIgA per minute was elevated by capsaicin stimulation. Salivary α-amylase activity and HRV analysis demonstrated an elevation of sympathetic nervous activity induced by capsaicin. EEG analysis showed a significant increase in beta band power. Conclusion: These results suggest that oral stimulation with capsaicin may be effective in improving oral conditions by increasing salivary flow and SIgA secretion, and in enhancing physical and mental conditions as indicated by sympathetic nerve and EEG changes.

Eating food is one of the most complicated behaviours in mammals, especially humans. The primary function of ghrelin is regulation of the appetite level and its stimulation. It is also responsible for the body’s energy balance and glucose homeostasis. Ghrelin has been shown to affect many brain structures, which confirms the presence of ghrelin receptors in the brain. Studies are also conducted to assess the possible role of ghrelin in anxiety states and in memory disorders and motor dysfunctions. Ghrelin has been found in saliva and salivary glands, teeth and gums, and in the taste buds of the tongue epithelium; it is also secreted by mucosal cells and gingival fibroblasts. The presence of ghrelin in developmental enamel, especially in odontoblasts and ameloblasts, may suggest its regulatory role in the development of teeth. Patients with chronic periodontitis have significantly higher concentrations of ghrelin in the peripheral blood serum, as compared to the control group. Ghrelin plays a special role in the proliferation of cancer cells and in the development of neoplastic metastases. The abundant presence of ghrelin receptors in cancer cells is considered an important target in the treatment of neoplasms. Ghrelin is a hormone whose multidirectional mechanism of action has not yet been fully understood. However, its ubiquitous occurrence in the human body and its very diverse participation in metabolic processes may prove to be a significant obstacle in achieving the expected clinical effect of ghrelin as an effective drug in selected disease units. [ABSTRACT FROM AUTHOR]

PURPOSE. Prevention of xerostomia and stress is important to prolong healthy life expectancy and improve the quality of life. We aimed to investigate the effects of tongue rotation exercise for increasing salivary secretions and stabilizing salivary stress hormone levels. MATERIALS AND METHODS. Twenty four participants without subjective oral dryness were enrolled. The exercises comprised tongue rotation exercise and empty chewing. The salivary stress hormone level was measured using a Salivary Amylase Monitor. Unstimulated whole saliva volume and salivary amylase activity were measured before tongue rotation exercise or empty chewing and subsequently 5, 10, and 15 minutes after these exercises. Differences in the rates of change of unstimulated whole saliva volume and salivary amylase activity were analyzed by repeated measure analysis of variance. RESULTS. Statistically significant differences among the rates of change were not observed after empty chewing for unstimulated whole saliva volume and salivary amylase activity at the four measurement times. However, the rate of change of unstimulated whole saliva volume and salivary amylase activity were statistically significantly different among the four time points: before the tongue rotation exercise and 5, 10, and 15 minutes post-exercise (P<.05 and P<.01, respectively). CONCLUSION. Tongue rotation is effective in increasing saliva secretion, reducing stress, improving oral function, and extending healthy life expectancy. [ABSTRACT FROM AUTHOR]

We examined the relationship between hemodynamics in the three major salivary glands and salivary secretion in urethane-anesthetized and sympathectomized type 2 diabetic and nondiabetic rats via laser speckle imaging and by collecting the saliva. Lingual nerve stimulation elicited rapid increases in glandular blood flow and induced salivary secretion from the three glands in both diabetic and nondiabetic rats. In the parotid gland, the magnitude of blood flow increase and salivary secretion was significantly lower in the diabetic rats when compared with the nondiabetic rats; however, this was not observed in the other glands. Although the intravenous administration of acetylcholine increased blood flow in the parotid gland in a dose-dependent manner, the response was significantly lower in the diabetic rats when compared with the nondiabetic rats. Similarly, mRNA expression levels of M1 and M3 muscarinic acetylcholine receptors in the parotid gland were relatively lower in the diabetic rats compared with the nondiabetic rats. Our results indicate that type 2 diabetes impairs parasympathetic vasodilation and salivary secretion in the parotid gland and suggest that disturbances in the cholinergic vasodilator pathway may contribute to the underlying mechanisms involved in the disruption of parasympathetic nerve-mediated glandular vasodilation. [ABSTRACT FROM AUTHOR]

Cigarette's smoke can affect the function of the receptor that relates to a change of salivary flow rate. The change of salivary function has the effect of increasing the number of the facultative anaerobic bacterial colony in the oral cavity of smoker that could lead to various dental and oral diseases. The purpose of this study is to measure salivary secretion and count the number of the facultative anaerobic bacterial colony of female smokers. This research is observation descriptive. The subjects were female smokers with an age range of 19-25 years. Saliva samples were taken by spitting method. The salivary flow rate was measured based on salivary volume. Salivary samples were diluted to 104 and then inoculated on the blood agar plate and then incubated at 37°C for 18-24 hours in the anaerobic facultative environment. The last step was counting the number of facultative anaerobic bacterial colony used colony counter. The results showed that the average of salivary secretion in female smokers as much as 0.289 mL/min. The number of the facultative anaerobic bacterial colony in female smokers as much as (167.63 ± 43.16) x 105 CFU / mL. The conclusion of this research is, in the mouth of female smokers was found the salivary flow rate indicated oligosialia and the number of the facultative anaerobic bacterial colony as much as (167.63 ± 43.16) x 105 CFU/mL. [ABSTRACT FROM AUTHOR]

Coriander is a popular herb with versatile applications. However, the current research about coriander medicinal values have been mainly focusing on its extracts while lacking in the relationship between living coriander plants and emotion. Therefore, this study aims to investigate the effects of coriander plants on human emotions and physiological activities. The results showed that the main Volatile organic compounds (VOCs) of coriander plants were 2-ethyl-1-hexanol, d-limonene, eucalyptol, benzyl alcohol, Isophorone, dimethyl glutarate, α-terpineol, styrene, methyl methacrylate, α-pinene. Coriander plants could significantly reduce the angry sub-scores, alpha amylase and amino acids (arginine, proline, histidine, and taurine) concentrations in saliva. Theta (4–8 Hz) band activity of the cerebral cortex was significantly enhanced. Moreover, taurine significantly positively correlated with anger and negatively correlated with vigor. All the results signified that coriander plant could influence the activity of brain electrophysiological and salivary secretion through its VOCs to improve people’s negative emotions.

Abstract Background To examine if patients with oral lichen planus, oral lichenoid lesions and generalised stomatitis and concomitant contact allergy have more frequent and severe xerostomia, lower unstimulated and chewing-stimulated saliva and citric-acid-stimulated parotid saliva flow rates, and higher salivary concentration of total protein and sIgA than cases without contact allergy and healthy controls. Methods Forty-nine patients (42 women, aged 61.0 ± 10.3 years) and 29 healthy age- and gender-matched subjects underwent a standardised questionnaire on general and oral health, assessment of xerostomia, clinical examination, sialometry, mucosal biopsy and contact allergy testing. Results Nineteen patients had oral lichen planus, 19 patients had oral lichenoid lesions and 11 patients had generalised stomatitis. 38.8% had contact allergy. Xerostomia was significantly more common and severe in patients (46.9%) than in healthy controls, whereas the saliva flow rates did not differ. The patients had higher sIgA levels in unstimulated and chewing-stimulated saliva than the healthy controls. The total protein concentration in saliva was lower in the unstimulated saliva samples whereas it was higher in the chewing stimulated saliva samples from patients when compared to healthy controls. The differences were not significant and they were irrespective of the presence of contact allergy. Conclusion Xerostomia is prevalent in patients with oral lichen planus, lichenoid lesions and generalised stomatitis, but not associated with salivary gland hypofunction, numbers of systemic diseases or medications, contact allergy, age, or gender. Salivary sIgA levels were higher in patients than in healthy controls, but did not differ between patient groups. The total salivary protein concentration was lower in unstimulated saliva samples and higher in chewing-stimulated saliva samples in patients than in healthy controls, but did not differ between patient groups. Our findings do not aid in the discrimination between OLP and OLL and these conditions with or without contact allergic reactions.

Abstract Sjögren's syndrome (SS) is an autoimmune exocrinopathy associated with severe secretory alterations by disruption of the glandular architecture integrity, which is fundamental for a correct function and localization of the secretory machinery. Syt-1, PI(4,5)P 2 and Ca2+ are significant factors controlling exocytosis in different secretory cells, the Ca2+ role being the most studied. Salivary acinar cells from SS-patients show a defective agonist-regulated intracellular Ca2+ release together with a decreased IP3R expression level, and this condition may explain a reduced water release. However, there are not reports where Syt-1, PI(4,5)P 2 and Ca2+ in acinar cells of SS patients had been studied. In the present study, we analyzed the expression and/or localization of Syt-1 and PI(4,5)P 2 in acinar cells of labial salivary gland biopsies from SS-patients and control individuals. Also, we evaluated whether the overexpression of Syt-1 and the loss of cell polarity induced by TNF-α or loss of interaction between acinar cell and basal lamina, alters directionality of the exocytosis process, Ca2+ signaling and α-amylase secretion in a 3D-acini model stimulated with cholinergic or β-adrenergic agonists. In addition, the correlation between Syt-1 protein levels and clinical parameters was evaluated. The results showed an increase of Syt-1 mRNA and protein levels, and a high number of co-localization points of Syt-1/STX4 and PI(4,5)P 2 /Ezrin in the acinar basolateral region of LSG from SS-patients. With regard to 3D-acini, Syt-1 overexpression increased exocytosis in the apical pole compared to control acini. TNF-α stimulation increased exocytic events in the basal pole, which was further enhanced by Syt-1 overexpression. Additionally, altered acinar cell polarity affected Ca2+ signaling and amylase secretion. Overexpression of Syt-1 was associated with salivary gland alterations revealing that the secretory dysfunction in SS-patients is linked to altered expression and/or localization of secretory machinery components together with impaired epithelial cell polarity. These findings provide a novel insight on the pathological mechanism implicated in ectopic secretory products to the extracellular matrix of LSG from SS-patients, which might initiate inflammation. Highlights • Syt-1 is overexpressed and mislocated in SG from SS-patients (64). • Syt-1 overexpression and TNF-α stimulation changes the secretion polarity (82). • Altered cell polarity affects Ca2+ signaling and amylase secretion (71). • Syt-1 overexpression correlates with secretory dysfunction parameters in SS-patients (85). • Strong association between Syt-1 overexpression with ESSDAI in SS-patients (74). [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

New Findings: What is the central question of this study?The effects of Ca2+ responses on salivary fluid secretion have been studied indirectly by monitoring ion channel activities and other indices. Therefore, Ca2+ responses during salivary secretion remain poorly understood.What is the main finding and its importance?Herein, we developed a simultaneous monitoring system for Ca2+ responses and salivary secretion in live animals using a YC‐Nano50‐expressing submandibular gland and a fibre‐optic pressure sensor. This new approach revealed a clear time lag between the onset of Ca2+ responses and salivary secretion. We also estimated the [Ca2+]i and provided direct evidence for the regulation of salivary secretion by small increases in [Ca2+]i in submandibular gland acinar cells. We monitored changes in [Ca2+]i during salivary secretion in the rat submandibular gland in live animals using a combination of intravital Ca2+ imaging with the ultrasensitive Ca2+ indicator YC‐Nano50 and a fibre‐optic pressure sensor. Intravenous infusion of ACh (10–720 nmol min−1) increased [Ca2+]i and salivary flow rate in a dose‐dependent manner. Repetitive stimulation with ACh induced equivalent Ca2+ responses and salivary secretion in the same individual animals. The accurate ACh stimulation experiments revealed a clear time lag between the onset of the increase in [Ca2+]i and salivary secretion. The time lag with the lowest dose of ACh (30 nmol min−1) was 106 s, which shortened to 19 s with the dose used for maximal salivary secretion (360 nmol min−1). This time lag might reflect the time required for [Ca2+]i to reach the level required to activate molecules for fluid secretion. The resting [Ca2+]i in submandibular gland was 37 nm, and [Ca2+]i at the onset of salivary secretion was 45–57 nm, irrespective of ACh dose. These results indicate that low [Ca2+]i is sufficient to trigger fluid secretion in the rat submandibular gland in vivo. [ABSTRACT FROM AUTHOR]

Introduction: Peripheral correlates of age-associated cognitive decline are important tools in the screening for potentially abnormal courses of cognitive aging. Since salivary gland function is controlled by the autonomic and central nervous system, associations between cognitive changes and salivary gland hypofunction were tested in two groups of middle-aged men in late midlife, who differed substantially with respect to their midlife performance in verbal intelligence when compared with their performance in young adulthood.Materials and Methods: Participants (n = 193) were recruited from the Danish Metropolit Cohort of men born in 1953. Based on their individual change in performance in two previously administered intelligence tests, they were allocated to one group of positive and one group of negative outliers in midlife cognition scores, indicating no decline versus decline in test performance. All participants underwent a clinical oral examination including assessments of their dental, periodontal, and mucosal conditions. Whole and parotid saliva flow rates were measured, and the number of systemic diseases and medication intake as well as daytime and nocturnal xerostomia were registered.Results: Participants with decline in cognitive test performance in midlife had significantly lower unstimulated whole saliva flow rates, higher prevalence of hyposalivation and daytime xerostomia and a higher caries experience than participants with no decline in midlife performance. Daytime and nocturnal xerostomia were associated with daily intake of medication and alcohol.Discussion: Overall, hyposalivation, xerostomia and poor dental status distinguished a group of men displaying relative decline in cognitive performance from a group of men without evidence of cognitive decline. Thus, hyposalivation and poor dental health status may represent potential correlates of age-related cognitive decline in late midlife, provided that other causes can be excluded.

Cystic fibrosis (CF) is a fatal genetic disease associated with widespread exocrine gland dysfunction. Studies have suggested activating effects of resveratrol, a naturally-occurring polyphenol compound with antioxidant and anti-inflammatory properties, on CF transmembrane conductance regulator (CFTR) protein function. We assayed, in F508del-CFTR homozygous (CF) and in wild-type mice, the effect of resveratrol on salivary secretion in basal conditions, in response to inhibition by atropine (basal β-adrenergic-dependent component) and to stimulation by isoprenaline (CFTR-dependent component). Both components of the salivary secretion were smaller in CF mice than in controls. Two hours after intraperitoneal administration of resveratrol (50 mg/kg) dissolved in DMSO, the compound was detected in salivary glands. As in both CF and in wild-type mice, DMSO alone increased the response to isoprenaline in males but not in females, the effect of resveratrol was only measured in females. In wild-type mice, isoprenaline increased secretion by more than half. In CF mice, resveratrol rescued the response to isoprenaline, eliciting a 2.5-fold increase of β-adrenergic-stimulated secretion. We conclude that the salivary secretion assay is suitable to test DMSO-soluble CFTR modulators in female mice. We show that resveratrol applied in vivo to mice reaches salivary glands and increases β-adrenergic secretion. Immunolabelling of CFTR in human bronchial epithelial cells suggests that the effect is associated with increased CFTR protein expression. Our data support the view that resveratrol is beneficial for treating CF. The salivary secretion assay has a potential application to test efficacy of novel CF therapies.

Objectives Environmental factors in the aetiology of primary Sjögren's syndrome (pSS) are largely unknown. Host–microbiome interaction at mucosal surfaces is presumed to be involved in the aetiopathogenesis of pSS. Here, we assessed whether the microbiome of the buccal mucosa is specific for pSS compared with symptom-controls. Methods The bacterial composition of buccal swab samples from 37 pSS patients, 86 non-SS sicca patients (with similar dryness symptoms to pSS patients, but not fulfilling the classification criteria) and 24 healthy controls (HCs) was determined with 16S rRNA sequencing. Multivariate Association with Linear Models was used to find associations between individual taxa and pSS, taking into account smoking and dental status. Associations were replicated in a general population cohort (n = 103). Results The buccal mucosa microbiome of pSS and non-SS sicca patients both differed from HCs. A higher Firmicutes/Proteobacteria ratio was characteristic for both pSS and non-SS sicca patients. Disease status (pSS, non-SS sicca, HCs) and salivary secretion rate contributed almost equally to the variation in bacterial composition between individuals (3.8 and 4.3%, respectively). Two taxa were associated with pSS compared with non-SS sicca patients and 19 compared with HCs. When salivary secretion rate was taken into account, no taxon was associated with pSS compared with non-SS sicca. Twelve of the 19 pSS-associated taxa were correlated with salivary secretion. Conclusion Dysbiosis of the buccal mucosa microbiome in pSS patients resembles that of symptom-controls. The buccal mucosa microbiome in pSS patients is determined by a combination of reduced salivary secretion and disease-specific factors. [ABSTRACT FROM AUTHOR]

Cholinergic agonists evoke elevations of the cytoplasmic free‐calcium concentration ([Ca2+]i) to stimulate fluid secretion in salivary glands. Salivary flow rates are significantly reduced in diabetic patients. However, it remains elusive how salivary secretion is impaired in diabetes. Here, we used an ex vivo submandibular gland perfusion technique to characterize the dependency of salivary flow rates on extracellular glucose concentration and activities of glucose transporters expressed in the glands. The cholinergic agonist carbachol (CCh) induced sustained fluid secretion, the rates of which were modulated by the extracellular glucose concentration in a biphasic manner. Both lowering the extracellular glucose concentration to less than 2.5 mM and elevating it to higher than 5 mM resulted in decreased CCh‐induced fluid secretion. The CCh‐induced salivary flow was suppressed by phlorizin, an inhibitor of the sodium–glucose cotransporter 1 (SGLT1) located basolaterally in submandibular acinar cells, which is altered at the protein expression level in diabetic animal models. Our data suggest that SGLT1‐mediated glucose uptake in acinar cells is required to maintain the fluid secretion by sustaining Cl− secretion in real‐time. High extracellular glucose levels may suppress the CCh‐induced secretion of salivary fluid by altering the activities of ion channels and transporters downstream of [Ca2+]i signals. [ABSTRACT FROM AUTHOR]

Background/purpose Although it has been reported that capsaicin ingestion has effects of protecting stomach mucosa and promoting energy consumption, physiological responses to oral stimulation with capsaicin has not been elucidated. Therefore, we investigated the effect of oral capsaicin stimulation on oral health and mental conditions by measuring changes in salivation, autonomic nervous activity and electroencephalogram (EEG). Materials and methods Eighteen healthy adults participated in this study. The stimulus concentrations of capsaicin and five basic taste solutions were determined based on the measured threshold of each stimulus in each subject. The weight of secreted saliva and the changes in concentrations of salivary secretory immunoglobulin A (SIgA) induced by capsaicin and taste stimuli were measured. Salivary α-amylase activity and heart rate variability (HRV) were measured as indicators of autonomic nervous activity. From EEG, psychological condition was analyzed by measuring the powers of theta, alpha, and beta bands. Results The salivary secretion rate was significantly increased by stimulation with capsaicin, NaCl, and citric acid compared with deionized water, and capsaicin demonstrated the most potent effect among tested stimuli. The secreted amount of SIgA per minute was elevated by capsaicin stimulation. Salivary α-amylase activity and HRV analysis demonstrated an elevation of sympathetic nervous activity induced by capsaicin. EEG analysis showed a significant increase in beta band power. Conclusion These results suggest that oral stimulation with capsaicin may be effective in improving oral conditions by increasing salivary flow and SIgA secretion, and in enhancing physical and mental conditions as indicated by sympathetic nerve and EEG changes. [ABSTRACT FROM AUTHOR]

Introduction: Peripheral correlates of age-associated cognitive decline are important tools in the screening for potentially abnormal courses of cognitive aging. Since salivary gland function is controlled by the autonomic and central nervous system, associations between cognitive changes and salivary gland hypofunction were tested in two groups of middle-aged men in late midlife, who differed substantially with respect to their midlife performance in verbal intelligence when compared with their performance in young adulthood. Materials and Methods: Participants (n D 193) were recruited from the Danish Metropolit Cohort of men born in 1953. Based on their individual change in performance in two previously administered intelligence tests, they were allocated to one group of positive and one group of negative outliers in midlife cognition scores, indicating no decline versus decline in test performance. All participants underwent a clinical oral examination including assessments of their dental, periodontal, and mucosal conditions. Whole and parotid saliva flow rates were measured, and the number of systemic diseases and medication intake as well as daytime and nocturnal xerostomia were registered. Results: Participants with decline in cognitive test performance in midlife had significantly lower unstimulated whole saliva flow rates, higher prevalence of hyposalivation and daytime xerostomia and a higher caries experience than participants with no decline in midlife performance. Daytime and nocturnal xerostomia were associated with daily intake of medication and alcohol. Discussion: Overall, hyposalivation, xerostomia and poor dental status distinguished a group of men displaying relative decline in cognitive performance from a group of men without evidence of cognitive decline. Thus, hyposalivation and poor dental health status may represent potential correlates of age-related cognitive decline in late midlife, provided that other causes can be excluded. [ABSTRACT FROM AUTHOR]

BACKGROUND AND OBJECTIVE: Chronic renal failure may affect the oral cavity because of the variety of metabolic and pathophysiologic changes. The aim of this study was to compare the xerostomia in unstimulated and pilocarpine-stimulated whole saliva of hemodialysis patients with the control group. METHODS: This cross-sectional study was conducted on 30 hemodialysis patients aged range of 35 to 65 and 30 healthy volunteers as control group. Patients’ individual data such as age, sex and duration of hemodialysis and their complaining of xerostomia, taste change and malodor were recorded. The xerostomia status of patients was evaluated by filling out the standard questionnaires. To determine the salivary changes unstimulated and pilocarpine-stimulated whole saliva was collected from both the patient and the control groups.. FINDINGS: Complaining of xerostomia was the most common oral manifestations among the patients. Dry mouth , taste change and malodor were recorded in 19 (63.3%), 14 (46.7%) and 14 (46.7%) of the patients, respectively. The unstimulated whole saliva was significantly lower in hemodialysis patients compared toin the control group (p

Tolterodine, a nonselective muscarinic antagonist available only as immediate release (IR) or extended release (ER) oral formulations, is used for the treatment of overactive bladder (OAB). This study aimed to compare the efficacy and extent of dry mouth adverse effects of tolterodine transdermal patch to the oral formulation. The two formulations have been examined through the muscarinic receptor binding tests conducted in bladder and salivary gland tissues and the salivary secretion tests conducted in rats. Comparable average tolterodine blood concentration levels were obtained 3 h after oral administration of tolterodine 25 mg/kg and 12 h after transdermal application of tolterodine patch 6 mg/8 cm. While K in the bladder tissue increased to a similar degree in both formulations of tolterodine, K in the salivary gland increased to a greater degree in the oral formulation. These results indicate that similar degree of inhibitory effects were observed in the bladder for both formulations while less inhibitory effects were observed in the salivary gland with tolterodine transdermal formulation compared to the oral formulation. For assessment of salivary secretion, tolterodine transdermal patch 6 mg/8 cm application resulted in significantly less inhibitory effects than oral tolterodine 25 mg/kg. Therefore, this study suggests that tolterodine transdermal patch could be a useful formulation that provides uniform and consistent inhibitory effects to effectively control OAB symptoms with reduced severity of dry mouth in comparison to the oral formulation. [ABSTRACT FROM AUTHOR]

Although a direct link has been established between self-experienced disgust and salivary secretion, it is unclear whether this physiological index is modulated by the social experience of disgust (i.e., exposure to the facial expression of disgust). We tested this issue in a pilot study by collecting salivary samples in a group of 20 healthy humans watching pictures of faces expressing disgust. Moreover, we tried to replicate previous evidence by testing saliva secretion in response to pictures of unpalatable (i.e., rotten) food and non-gustatory disgusting stimuli (i.e., disgusting insects). Overall, our analysis shows a general reduction of saliva secretion in response to disgust stimuli, compared to their positive counterparts, although further analyses for specific stimulus categories indicated that this difference was statistically significant only for food pictures. The non-significance of the face and insect categories might be due to insufficient power of our small sample. Overall, a general reduction of saliva secretion for different disgust-related stimuli suggests a shared mechanism of encoding, in line with theories of neural reuse. [ABSTRACT FROM AUTHOR]

Background: To examine if patients with oral lichen planus, oral lichenoid lesions and generalised stomatitis and concomitant contact allergy have more frequent and severe xerostomia, lower unstimulated and chewing-stimulated saliva and citric-acid-stimulated parotid saliva flow rates, and higher salivary concentration of total protein and sIgA than cases without contact allergy and healthy controls. Methods: Forty-nine patients (42 women, aged 61.0 ± 10.3 years) and 29 healthy age- and gender-matched subjects underwent a standardised questionnaire on general and oral health, assessment of xerostomia, clinical examination, sialometry, mucosal biopsy and contact allergy testing. Results: Nineteen patients had oral lichen planus, 19 patients had oral lichenoid lesions and 11 patients had generalised stomatitis. 38.8% had contact allergy. Xerostomia was significantly more common and severe in patients (46.9%) than in healthy controls, whereas the saliva flow rates did not differ. The patients had higher sIgA levels in unstimulated and chewing-stimulated saliva than the healthy controls. The total protein concentration in saliva was lower in the unstimulated saliva samples whereas it was higher in the chewing stimulated saliva samples from patients when compared to healthy controls. The differences were not significant and they were irrespective of the presence of contact allergy. Conclusion: Xerostomia is prevalent in patients with oral lichen planus, lichenoid lesions and generalised stomatitis, but not associated with salivary gland hypofunction, numbers of systemic diseases or medications, contact allergy, age, or gender. Salivary sIgA levels were higher in patients than in healthy controls, but did not differ between patient groups. The total salivary protein concentration was lower in unstimulated saliva samples and higher in chewing-stimulated saliva samples in patients than in healthy controls, but did not differ between patient groups. Our findings do not aid in the discrimination between OLP and OLL and these conditions with or without contact allergic reactions. [ABSTRACT FROM AUTHOR]

Objectives The purpose of this study was to determine whether rebamipide, an antistomach ulcer agent, ameliorated benzodiazepine-induced hyposalivation in rat parotid gland ( PG) and submandibular gland ( SMG). Methods Saliva was collected from PG and SMG through a capillary cannula inserted into the parotid duct and sublingual papillae, respectively, every 15 min for 1 h after stimulation with pilocarpine dissolved in physiological saline and intraperitoneally administered at 1 mg kg−1. Diazepam ( DZP) was administered intraperitoneally at a dose of 0.2 mg kg−1 twice daily for 7 days. Rebamipide was administered at 10, 20, 30, or 100 mg kg−1 concomitantly with DZP to determine its effect on hyposalivation. The effect of rebamipide on movement of intracellular calcium ([Ca2+] i) in isolated parotid acinar cells was analyzed using Fluo4, a fluorescent dye used to detect Ca2+. Results Repetitive administration of DZP decreased salivary secretion in PG and SMG. This inhibitory effect was weakened by administration of rebamipide. Prior administration of DZP (10−6M) significantly suppressed carbachol (10−7M)-induced increase in [Ca2+] i. This inhibitory effect was ameliorated by combined use with rebamipide (5 × 10−4M). Conclusion This findings suggest that rebamipide weakens the downregulatory effect of DZP on salivary secretion by preventing DZP-induced suppression of increase in [Ca2+] i. [ABSTRACT FROM AUTHOR]

Fluid and ion secretion from the submandibular gland ( SMG) is mainly regulated by parasympathetic nerves. This study evaluated the effect of parasympathectomy on salivary secretion from normal and irradiated rat SMGs from 1 to 24 wk after denervation. Although stimulated salivary secretion was significantly lower in denervated SMGs compared with contralateral self-controls, the resting salivary flow rates were markedly higher in the denervated SMGs at 1, 12, and 24 wk after denervation. The levels of muscarinic acetylcholine M1 and M3 receptors, as well as of aquaporin 5, were up-regulated. Notably, although irradiated SMGs showed significantly lower resting and stimulated salivary secretion rates than non-irradiated SMGs, the resting salivary secretion rates of the irradiated and denervated SMGs were markedly higher than seen in the irradiated self-control SMGs at 1, 12, and 24 wk after parasympathectomy, and were even higher than seen in the non-irradiated sham-operated rats. The expression of M1 and M3 receptors was similarly elevated. Taken together, our results suggest that parasympathetic denervation increases resting salivary secretion of both normal and irradiated SMGs. This approach might provide a potential modality for relieving radiation-induced xerostomia, which is a common complication following treatment of head and neck cancer. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to validate a Spanish cross-cultural adaptation of the xerostomia inventory (XI).Materials and Methods: The original English version of XI was translated into Spanish, cross-culturally adapted and field tested. The Spanish version of XI (XI-Sp) was tested with a sample of 41 patients with xerostomia. The reliability of the XI-Sp was determined through internal consistency and test-retest methods. The construct validity of XI-Sp was determined by means of correlation between XI-Sp scores and salivary flow measurements.Results: Overall XI-Sp scores were 40.8 (SD = 10) for the first application and 40.2 (SD = 9.5) for the second. Cronbach's alpha value for the XI-Sp was 0.89 and 0.87, respectively, while interitem correlation averages were r = 0.44 and r = 0.39 for each application. Interitem correlation and corrected total was rc ≥0.30. The test-retest intraclass correlation coefficient value for the XI-Sp score was 0.59 and 0.91. Convergent validity for construct validity correlation with salivary flow showed a medium effect size (r2  = 0.10) for the first application but did not make a statistically significant prediction for the second (r2  = 0.7).Conclusions: This study provides evidence concerning the reliability of the XI-Sp, showing that it may be a useful tool for Spanish-speaking xerostomia patients for both clinical and epidemiologic research. [ABSTRACT FROM AUTHOR]

During dental sedation, control of the cough reflex is crucial for a safe and smooth procedure. Accumulated saliva is one of the predisposing factors for coughing. Body movements during dental sedation appear to enhance salivation. Therefore, the aim of this study was to investigate the difference in salivary secretion between the with-movements state and the without-movements state during sedation. Salivary weight for 1 min was measured 3 times in 27 patients with intellectual disability during dental treatment under deep sedation with midazolam and propofol. The observed variables were body movements, bispectral index (BIS), and predicted propofol effect-site concentration. A total of 81 measurements were classified into the with-movements state (n = 39; ie, measurements during which body movements were observed) or the without-movements state (n = 42; ie, measurements during which no body movements were observed). The median salivary weight was significantly smaller in the without-movements state compared with the with-movements state (0.03 vs 0.11 g, P < .0001). The BIS was significantly lower in the without-movements state. There was no significant difference in the predicted propofol effect-site concentration between the 2 states. Significant correlation was observed between salivary weight and BIS in the with-movements state (r = 0.44, P = .004). The findings indicate that salivary secretion decreased according to deep sedation. Furthermore, immobility also reduced salivary secretion. We concluded that one reason that immobility is beneficial is because of the resulting decreased salivary secretion during dental treatment under deep sedation. [ABSTRACT FROM AUTHOR]

The goal of this study was to formulate and evaluate side effects of transdermal delivery of proniosomal gel compared to oral tolterodine tartrate (TT) for the treatment of overactive bladder (OAB). Proniosomal gels are surfactants, lipids and soy lecithin, prepared by coacervation phase separation. Formulations were analyzed for drug entrapment efficiency (EE), vesicle size, surface morphology, attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy, in vitro skin permeation, and in vivo effects. The EE was 44.87%-91.68% and vesicle size was 253-845 nm for Span formulations and morphology showed a loose structure. The stability and skin irritancy test were also carried out for the optimized formulations. Span formulations with cholesterol-containing formulation S1 and glyceryl distearate as well as lecithin containing S3 formulation showed higher cumulative percent of permeation such as 42% and 35%, respectively. In the in vivo salivary secretion model, S1 proniosomal gel had faster recovery, less cholinergic side effect on the salivary gland compared with that of oral TT. Histologically, bladder of rats treated with the proniosomal gel formulation S1 showed morphological improvements greater than those treated with S3. This study demonstrates the potential of proniosomal vesicles for transdermal delivery of TT to treat OAB. [ABSTRACT FROM AUTHOR]

Context: Overactive bladder (OAB) is a common problem and anticholinergic drugs are first-line therapy, but they have side effects. Objective: Development of oxybutynin chloride (OC) proniosomal gels and analyses of its efficacy for OAB treatment. Materials and methods: Phase separation coacervation was used to prepare proniosomal gels using various non-ionic surfactants, lipids, soy lecithin and isopropyl alcohol. Gels were characterized with regard to entrapment efficiency (EE), vesicle size, surface morphology (using environmental scanning electron microscopy [E-SEM]), stability, attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy,in vitroskin permeation,in vivoanimal studies and histopathology. Results and discussion: EE was 87–92%, vesicle size was 0.38–5.0 μm, and morphology showed some loosened pores in proniosomes after hydration. ATR-FTIR spectroscopy showed no significant shifts in peaks corresponding to OC and excipients. Most formulations exhibited >50% permeation but the cholesterol-containing formulations P3 (Span 20:Span 60 [1:1]) and P4 [Tween 20:Tween 80 (1:1)] had the highest percent cumulative permeation. P3 and P4 also showed faster recovery of cholinergic effects on salivary glands than oral formulations. P3 and P4 had pronounced therapeutic effects in reduction of urinary frequency and demonstrated improvements in bladder morphology (highly regenerative surface of the transitional epithelium). Conclusion: These results suggest that OC could be incorporated into proniosomal gels for transdermal delivery in the treatment of OAB. [ABSTRACT FROM PUBLISHER]

Objective Desipramine is a tricyclic antidepressant with a negative side effect of dry mouth. The Na+/H+ exchanger was suggested to be a target of desipramine in salivary gland cells. However, it is unclear whether desipramine has other targets in the salivary secretion pathway. Here, we studied the effect of desipramine on salivary Ca2+ signaling. Materials and Methods Cytosolic free Ca2+ concentration ([Ca2+]i) was determined with the fluorescent Ca2+ indicator fura-2/ AM. Aquaporin translocation was analyzed by Western blotting and immunocytochemistry of confocal microscopy. Results Desipramine inhibited the carbachol- and histamine-mediated increase in cytosolic Ca2+ ([Ca2+]i) in a concentration-dependent manner. However, desipramine did not affect increases in [Ca2+]i mediated by extracellular ATP, sphingosine-1-phosphate, or thapsigargin. The adrenergic receptor blockers prazosin and propranolol did not reverse the desipramine-mediated inhibition of carbachol- and histamine-induced increases in [Ca2+]i. We also found that desipramine inhibits the increase in membrane aquaporin-5 level triggered by carbachol and histamine treatments. Conclusions These results imply that desipramine blocks muscarinic and histamine receptor-mediated Ca2+ signaling and the subsequent translocation of aquaporin-5 in human salivary gland cells, suggesting a novel mechanism for the xerogenic effects of desipramine. [ABSTRACT FROM AUTHOR]

Background Salivary glands are comprised predominantly of two epithelial cell types, acinar and ductal cells. Activation of muscarinic acetylcholine receptors on acinar cells induces inositol 1,4,5-trisphosphate-mediated Ca 2+ release from intracellular Ca 2+ stores, followed by Ca 2+ influx across the plasma membrane. The increase in intracellular Ca 2+ concentration ([Ca 2+ ] i ) activates ion channels and transporters involved in fluid secretion; thus [Ca 2+ ] i acts as the primary fluid secretion signal in acinar cells. Highlight The development of Ca 2+ imaging techniques has enabled extensive study of spatiotemporal Ca 2+ dynamics in isolated acinar cells; however, the relationship between Ca 2+ responses and fluid secretion in vivo is not yet fully understood. In vivo Ca 2+ imaging in salivary gland cells is necessary for determining Ca 2+ responses during salivary secretion. Recently, we developed an intravital imaging system for monitoring Ca 2+ responses in rat submandibular gland (SMG) acinar cells in live animals using retrograde ductal injection of adenoviral vectors expressing the genetically encoded Ca 2+ indicator, YC-Nano50. Expression of YC-Nano50 was observed throughout the SMG, and we confirmed that YC-Nano50 was functional for monitoring Ca 2+ responses in SMG cells. Administration of acetylcholine significantly increased [Ca 2+ ] i in the SMG, and this increase gradually decreased to resting levels. Conclusion We successfully visualized agonist-induced Ca 2+ dynamics in SMG acinar cells in live animals. This novel experimental system represents a powerful tool for understanding the relationships between Ca 2+ responses and salivary secretion in vivo . [ABSTRACT FROM AUTHOR]

Aim The purpose of the present study was to evaluate the changes in oral health and function through an oral health educational program for the independent older people with xerostomia. Methods Community-dwelling older people with xerostomia aged over 65 years who participated in a preliminary comprehensive health survey in 2011 were recruited for the educational program. A total of 47 participants were randomly assigned into two groups, the intervention group ( n = 26) and the control group ( n = 21). The intervention group attended a 90-min oral health education program every 2 weeks for 3 months. The program consisted of oral hygiene instruction, facial and tongue muscle exercise, and salivary gland massage. The control group was provided only general information about oral health. The assessments of oral function, such as oral diadochokinesis of articulation, swallowing, taste threshold and salivary flow rate, were carried out before and after 3 months with or without intervention. Results A total of 38 participants (21 of intervention group and 17 of control group) completed the study protocol. In the intervention group, resting salivation significantly improved after the program. The second and third cumulated Repetitive Saliva Swallowing Test times significantly improved in the intervention group. The threshold for bitterness significantly lowered in the intervention group, whereas the sour threshold significantly heightened in the control group after 3 months ( P < 0.05). Conclusions The present study suggests that the educational program targeting oral function improvement is effective among the independent older population. Geriatr Gerontol Int 2015; 15: 481-489. [ABSTRACT FROM AUTHOR]

To evaluate the role of the lateral hypothalamic area (LH) in the masticatory-salivary reflex, we investigated submandibular salivary secretion and the electromyographic (EMG) activity of the jaw-closer masseter muscle in sham-operated rats and rats with unilateral LH lesions. One week prior to surgery and recording, the rats were given daily experience of eating pellets; powder; or hard, medium or soft mash, all of which were composed of laboratory chow. Salivary secretion was induced during eating and grooming behavior. During eating, the powdered food induced the highest salivary flow rate, and the soft (wet) mash induced the lowest salivary flow rate. Conversely, the amount of food consumed (dry weight) was greatest when soft mash was provided and lowest when the powder or pellets (a dry diet) were provided. The EMG activity of the masseter muscle during eating was greatest during consumption of the pellets and weakest during consumption of the powder. LH lesions that were ipsilateral to the examined submandibular gland reduced salivary secretion to about 20–30% of the control value, whereas contralateral LH lesions reduced it to about 40–50% of the control value. Neither masseter muscle EMG activity nor food consumption was markedly affected by the presence of an LH lesion. These results suggest that the texture of food, especially its water content, affects the flow rate of saliva and that the LH is heavily involved in the masticatory-salivary reflex. [ABSTRACT FROM AUTHOR]

Objective In our current work, in vivo examination of AQP5 distribution in labial salivary glands following stimulation of secretion has been carried out in normal individuals and in patients with Sjögren's syndrome. Subjects and Methods For this study, we selected five patients with primary Sjögren's syndrome (mean age 62.4 ± 10.6 s.d. years) diagnosed in accordance with the European Cooperative Community classification criteria. There were five patients (mean age 27 ± 2.5 s.d. years) in the control group. The subcellular distribution of AQP5 in human labial gland biopsies was determined with light and immunoelectron microscopy before and 30 min after administration of oral pilocarpine. Results In unstimulated control and Sjögren's labial glands, AQP5 is about 90% localized in the apical plasma membrane, with only rarely associated gold particles with intracellular membrane structures. We have found no evidence of pilocarpine-induced changes in localization of AQP5 in either healthy individuals or patients with Sjögren's syndrome. Conclusions Our studies indicate that neither Sjögren's syndrome itself, nor muscarinic cholinergic stimulation in vivo caused any significant changes in the distribution of AQP5 in the labial salivary gland cells. [ABSTRACT FROM AUTHOR]