Reduction In Salivary Secretion Research Articles

In females, salivary secretion was significantly lower in patients with severe reflux esophagitis than in healthy controls.

The salivary secretion in patients with mild reflux esophagitis (RE) and non-erosive reflux disease is significantly lower in females, but not in males. However, sex differences in salivary secretion in patients with severe RE remain unknown. Therefore, the present study investigated sex differences in saliva secretion in patients with severe RE. Subjects consisted of 23 male patients with severe RE, 24 male healthy controls (HCs), 26 female patients with severe RE, and 25 female HCs. Saliva secretion was assessed as follows: each patient chewed sugarless gum for 3min prior to endoscopy, and the amount and pH of saliva secreted before and after acid loading as an index of the acid-buffering capacity were measured. In males, no significant differences were observed in the amount of saliva secretion, salivary pH, or the acid-buffering capacity between severe RE patients and HCs. In females, the amount of saliva secretion (severe RE: 2.4 [1.8-4.1], HCs: 5.3 [3.4-7.5], p = 0.0017), salivary pH (severe RE: 7.0 [6.7-7.3], HCs: 7.2 [7.1-7.3], p = 0.0455), and the acid-buffering capacity (severe RE: 5.9 [5.3-6.2], HCs: 6.2 [6.1-6.5], p = 0.0024) were significantly lower in severe RE patients than in HCs. Among females, the salivary secretion was significantly lower in severe RE patients than in HCs. This reduction in salivary secretion may contribute to the pathophysiology of severe RE in females.

Gemigliptin Improves Salivary Gland Dysfunction in D-Galactose-Injected Aging Rats.

Oral dryness is among the most common conditions experienced by the elderly. As saliva plays a crucial role in maintaining oral health and overall quality of life, the condition is increasingly taking its toll on a rapidly growing aging population. D-galactose (D-gal) stimulates their formation, which in turn cause oxidative stress and accelerate age-related decline in physical function. In this study, we observed a reduction in salivary secretion and amylase levels in aged rats injected with D-gal, confirming salivary gland dysfunction. Treatment with gemigliptin increased DPP-4 inhibition and GLP-1 levels in the salivary glands of aging rats and reduced the expression of AGEs and receptors for advanced glycation end products (RAGE). This effect was caused by the presence of additional reactive oxygen species (ROS) in the salivary glands of the examined rats. Gemigliptin's cytoprotective effect reduced amylase and mucin accumulation and increased AQP5 expression, which are important indicators of salivary gland function. In sum, gemigliptin was shown to improve D-gal-induced decline in the salivary gland function of aged rats through its anti-glycation and antioxidant activities. Gemigliptin shows promise as a treatment strategy for patients experiencing decreased salivary function associated with their advancing age.

Inhibition of NLRP3 inflammasome activity by MCC950 leads to exacerbation of Sjӧgren's syndrome pathologies in non-obese diabetic mice.

Sjӧgren's syndrome (SS) is an autoimmune inflammatory disease characterized by chronic inflammation and dysfunction of exocrine glands and causes dry mouth, dry eyes and various systemic health problems. The objective of this study is to define the in vivo actions of the endogenous NLRP3 inflammasome, a key initiator and mediator of various immune and inflammatory conditions, in newly established SS disease. MCC950, a highly specific small-molecule inhibitor of NLRP3 inflammasome formation and activation, was intraperitoneally administered to the female non-obese diabetic (NOD) mice aged 11 weeks, which have newly established SS-like hyposalivation and pathologies. The injection was conducted three times weekly for three consecutive weeks and mice were analysed for characteristic SS pathologies at the end of the treatments. MCC950 treatment resulted in a marked reduction in salivary secretion and an exacerbation of leukocyte infiltration of submandibular glands. The disease-worsening effect of MCC950 treatment was accompanied by increased T and B cell numbers, enhanced T helper 1 response and reduced aquaporin 5 expression in submandibular glands. Hence, ablation of endogenous NLRP3 inflammasome activity by MCC950 with established autoimmune exocrinopathy exacerbates salivary gland dysfunction and inflammation, indicating a disease-alleviating and inflammation-dampening action of the endogenous NLRP3 inflammasome activity during established SS disease in the non-obese diabetic mouse model.

Long-Term Oral Administration of LLHK, LHK, and HK Alters Gene Expression Profile and Restores Age-Dependent Atrophy and Dysfunction of Rat Salivary Glands.

Xerostomia, also known as dry mouth, is caused by a reduction in salivary secretion and by changes in the composition of saliva associated with the malfunction of salivary glands. Xerostomia decreases quality of life. In the present study, we investigated the effects of peptides derived from β-lactoglobulin C on age-dependent atrophy, gene expression profiles, and the dysfunction of salivary glands. Long-term oral administration of Leu57-Leu58-His59-Lys60 (LLHK), Leu58-His59-Lys60 (LHK) and His59-Lys60 (HK) peptides induced salivary secretion and prevented and/or reversed the age-dependent atrophy of salivary glands in older rats. The transcripts of 78 genes were upregulated and those of 81 genes were downregulated by more than 2.0-fold (p ≤ 0.05) after LHK treatment. LHK upregulated major salivary protein genes such as proline-rich proteins (Prpmp5, Prb3, Prp2, Prb1, Prp15), cystatins (Cst5, Cyss, Vegp2), amylases (Amy1a, Amy2a3), and lysozyme (Lyzl1), suggesting that LLHK, LHK, and HK restored normal salivary function. The AP-2 transcription factor gene (Tcfap2b) was also induced significantly by LHK treatment. These results suggest that LLHK, LHK, and HK-administration may prevent and/or reverse the age-dependent atrophy and functional decline of salivary glands by affecting gene expression.

Juvenile Recurrent Parotitis: The Role of Sialendoscopy.

Juvenile recurrent parotitis (JRP) is a recurrent parotid inflammation of nonobstructive, nonsuppurative nature. It manifests in childhood and usually resolves after puberty but may also persist into adulthood. JRP is characterized by recurrent episodes of unilateral or/and bilateral parotid swelling with pain, reduction of salivary secretion, swallowing difficulty, fever, and malaise. The cause of this condition remains obscure. Throughout the last two decades, many therapeutic methods have been used in order to reduce the frequency and severity of JRP. During the acute episodes, conservative approaches (antibiotics, analgesics, sialogogues, massage of the parotid gland, and mouth rinses) are used. Parotidectomy has been suggested in rare selective occasions. Recently, a promising concept of sialendoscopy, which is a minimal invasive endoscopic technique, has been applied. This review outlines the literature on JRP focusing on methods and challenges in diagnosing JRP along with the differential diagnosis of JRP and the function of the parotid during JRP. In addition, we describe the treatment options for JRP, pointing out the importance of sialendoscopy as a diagnostic and treatment procedure that offers improvement in patients' daily life.

Switching to normal diet reverses kwashiorkor-induced salivary impairments via increased nitric oxide level and expression of aquaporin 5 in the submandibular glands of male Wistar rats.

Kwashiorkor, a form of malnutrition, has been shown to cause impaired salivary secretion. However, there is dearth of information on the mechanism that underlies this complication. Also, whether returning to normal diet after kwashiorkor will reverse these complications or not is yet to be discerned. Thus, this study aimed at assessing the mechanisms that underlie kwashiorkor-induced salivary impairments and to evaluate the effects of switching back to normal-diet on kwashiorkor-induced salivary impairments. Weaning rats were randomly divided into 3 groups (control group, kwashiorkor group (KG), re-fed kwashiorkor group (RKG)) of 7 rats each. The control group had standard rat chow while the KG and RKG were fed 2% protein diet for 6 weeks to induce kwashiorkor. The RKG had their diet changed to standard rat-chow for another 6 weeks. Blood and stimulated saliva samples were collected for the analysis of total protein, electrolytes, amylase, immunoglobulin A (IgA) secretion rate, leptin, and ghrelin. Tissue total protein, nitric oxide level, expressions of Na+/K+-ATPase, muscarinic (M3) receptor, and aquaporin 5 in the submandibular glands were also determined. Data were presented as means ± SEM and compared using ANOVA with Tukey's post hoc test. RKG showed improved salivary function evidenced by reduced salivary lag-time and potassium and increased flow rate, sodium, amylase, IgA secretion rate, leptin, submandibular nitric oxide level, and aquaporin 5 expression compared with KG. This study for the first time demonstrated that kwashiorkor caused significant reduction in salivary secretion through reduction of nitric oxide level and aquaporin 5 expression in submandibular salivary glands. Normal-diet re-feeding after kwashiorkor returned salivary secretion to normal.

Proteasome inhibition suppresses Th17 cell generation and ameliorates autoimmune development in experimental Sjögren's syndrome.

Immunoproteasome activation in immune cells is involved in the modulation of immune responses. Increasing evidence indicates that proteasome inhibitors show beneficial effects in treating autoimmune diseases, but it remains unclear whether proteasome inhibition is an effective approach for suppressing autoimmune development in Sjögren's syndrome (SS). Our previous work has demonstrated a critical role for Th17 cells in the development of experimental SS (ESS) in mice. In this study, we detected high levels of low-molecular-weight protein 7 (LMP7), a key subunit of the immunoproteasome, in Th17 cells from ESS mice. Moreover, treatment with bortezomib (BTZ), a proteasome inhibitor, markedly suppressed Th17 differentiation in both murine and human naive T cells in culture. Furthermore, ESS mice treated with BTZ displayed significantly higher saliva flow rates and a reduction in tissue destruction in the salivary glands compared with vehicle-treated ESS mice. Notably, BTZ-treated ESS mice showed markedly decreased Th17 cells, germinal center B cells and plasma cells in the peripheral lymphoid organs. In addition, adoptively transferred wild type naive CD4+ T cells rapidly differentiated into Th17 cells and induced salivary dysfunction in IL-17-deficient mice immunized for ESS induction. However, BTZ treatment profoundly suppressed the donor T-cell-derived Th17 response and ameliorated the reduction in salivary secretion in IL-17-deficient recipient mice. Taken together, our findings demonstrate that proteasome inhibition can effectively ameliorate ESS by suppressing the Th17 response, which may contribute to the development of a novel therapeutic strategy for the treatment of SS.Cellular &Molecular Immunology advance online publication, 10 July 2017; doi:10.1038/cmi.2017.8.

Proteasome inhibition ameliorates experimental Sjögren’s syndrome by suppressing Th17 and B cell responses

Abstract Primary Sjögren’s syndrome (SS) is a chronic autoimmune disease that mainly affects salivary and lacrimal glands. Currently, there is a lack of effective therapies for SS patients. Increasing evidence indicates that Bortezomib (BTZ), the first proteasome inhibitor approved for treating multiple myeloma, shows beneficial effects in treating lupus. Although clinical findings have revealed increased expression of proteasome in SS patients, it remains unclear whether proteasome inhibition is an effective approach for treating SS. In this study, we evaluated the therapeutic effects of BTZ on experimental SS (ESS) mouse model. Mice were immunized with proteins extracted from salivary glands (SG) to induce ESS and received either vehicle or BTZ treatment. Compared with vehicle-treated counterparts, BTZ-treated mice displayed markedly higher saliva flow rates and ameliorated tissue destructions accompanied with less lymphocytes infiltration in SG. Notably, mice with BTZ treatment showed significantly decreased Th17 but not Th1 responses, and reduced germinal center B cells and plasma cells in peripheral lymphoid organs. In culture, BTZ treatment significantly suppressed Th17 cells differentiation and proliferation. Moreover, adoptively transferred naïve CD4 T cells differentiated into Th17 cells and induced salivary dysfunction in immunized Il17a−/− mice. However, the BTZ-treated recipient mice exhibited suppressed Th17 responses with ameliorated reduction in salivary secretion. Taken together, our findings have shown that BTZ treatment can suppress Th17 and B cell responses and effectively ameliorate ESS development in mice, which may contribute to the validation of BTZ as a promising candidate for treating SS.

Effect of anti-asthmatic drugs on dental health: A comparative study.

Aims:Bronchial asthma constitutes important problem worldwide. This chronic lung disease has detrimental effect in the oral cavity like reduction of salivary secretion, change in salivary composition and pH.Materials and Methods:This study was conducted to compare the prevalence of dental caries in asthmatic children and healthy children, and also to evaluate the correlation between the Streptococcus mutans, Lactobacillus and dental caries in both the groups.Results:In this study, the mean decayed, missing, filled teeth score of children in the study group was (4.53 ± 3.38) higher than the control group (1.51 ± 1.58) (P < 0.01). The S. mutans count of the study group was (59574.47 ± 28510.67) higher than the control group (19777.78 ± 17899.83) P < 0.01. The Lactobacillus count in study group was (43553.19 ± 58776.96) higher than the control group (8843.84 ± 7982.72) P < 0.01. Subjects using inhaled corticosteroids were more prone to develop dental caries than the control group with odds ratio = 6.26 and 95% confidence interval.Conclusions:The dental caries prevalence increases with the usage of β2 agonist and corticosteroid inhalers for the treatment of asthma. Thus in asthmatic children, increase in caries prevalence might be due to the drug treatment and not due to the disease by itself. It can be concluded that asthmatic children have a higher prevalence of dental caries than healthy children. Hence, special oral health care is needed for asthmatic children.

Modulation of aquaporins expressions and its impact on alleviating diabetic complications in rats: role of Citrullus colocynthis

Background: Aquaporins (AQPs) belong to a class of small, integral membrane proteins that enable water transfer across the plasma membranes of cells as a reaction to osmotic gradients. There are 13 known types of AQPs in humans (AQP0 to AQP12), which are expressed in various organs such as the kidney, brain, liver, lungs, and salivary glands. In patient with diabetes mellitus, a reduction in salivary secretion is noted in concurrence with low salivary AQP5 levels. The Citrullus colocynthis (CC) extracts were reported to have beneficial effects on glucose homeostasis and body weight maintenance, in either alloxan- or streptozotocin (STZ)-induced diabetic rats through exerting insulinotropic effect. Aims and Objective: To check the changes in AQPs expression and to understand the antidiabetic effect of CC as a medicinal herb in STZ-induced diabetic rats. Materials and Methods: Forty-two male Wistar rats were assigned equally into six groups. The first and second groups were kept as control groups: the first remained without treatment, but the second received CC orally. Diabetes was induced by a single intraperitoneal (i.p) injection of STZ (60 mg/kg b.w.) in the remaining four groups. Three diabetic groups were treated with insulin or CC or both together for 4 weeks. The remaining diabetic group was left untreated as control diabetic group. Blood and organs were taken for biochemical, gene expression, and immunohistochemistry examinations. Result: Diabetic rats displayed increases in blood glucose, lipid profile, liver, and kidney parameters, which were restored significantly to normal with insulin or CC or both. At molecular level, diabetic rats showed significant downregulation in mRNA expressions of antioxidant enzymes, insulin receptor substrate 1 and 2, pyruvate kinase, GLUT-2 in liver and of AQP1, AQP5, AQP7, and AQP8 expressions in kidney, salivary gland, and pancreas, respectively, and normalized significantly by insulin or CC or in combination administrations. Expressions of phosphoenol pyruvate carboxykinase in liver and of AQP2 and AQP3 in kidney were upregulated in diabetic rats and returned to normal completely by insulin alone or CC or their combination. Values were statistically significant at p < 0.05. Immunohistochemical examinations revealed a downregulation of insulin and GLUT-2 in pancreas and upregulation of AQP2 in kidney of diabetic rats, but treatments with CC augmented insulin effect and restored their expression to normal levels. Conclusion: Current results concluded that AQPs could be a promising target for drug development. Moreover, Citrullus colocynthis extract acts as antidiabetic medicinal herb, which has been confirmed by its molecular and immunohistochemical effects.

X-Ray-Induced Damage to the Submandibular Salivary Glands in Mice: An Analysis of Strain-Specific Responses.

Radiation therapy for head and neck cancers often causes xerostomia (dry mouth) by acutely damaging the salivary glands through the induction of severe acute inflammation. By contrast, the mechanism underlying the X-ray-induced delayed salivary dysfunction is unknown and has attracted increasing attention. To identify and develop a mouse model that distinguishes the delayed from the acute effects, we examined three different mouse strains (C57BL/6, ICR, and ICR-nu/nu) that showed distinct T-cell activities to comparatively analyze their responses to X-ray irradiation. Three strains were irradiated with X-rays (25 Gy), and functional changes of the submandibular glands were examined by determining pilocarpine-induced saliva secretion. Structural changes were evaluated using histopathological and immunohistochemical examinations of CD3, cleaved poly (ADP-ribose) polymerase (PARP), and Bcl-xL. In C57BL/6 mice, the X-ray irradiation induced acute inflammation accompanied by severe inflammatory cell infiltration at 4 days postirradiation, causing substantial destruction and significant dysfunction at 2 weeks. Fibrotic repair was observed at 16 weeks. In ICR-nu/nu mice, the inflammation and organ destruction were much milder than in the other mice strains, but increased apoptotic cells and a significant reduction in salivary secretion were observed at 4 and 8 weeks and beyond, respectively. These results suggest that in C57BL/6 mice, X-ray-induced functional and structural damage to the salivary glands is caused mainly by acute inflammation. By contrast, although neither acute inflammation nor organ destruction was observed in ICR-nu/nu mice, apoptotic cell death preceded the dysfunction in salivary secretion in the later phase. These data suggest that the X-ray-irradiated ICR-nu/nu mouse may be a useful animal model for developing more specific therapeutic methods for the delayed dysfunction of salivary glands.

Use of Scopolamine Patches in Patients Treated With Parotidectomy

The antimuscarinic effect of scopolamine causes a reduction of salivary secretion, so it can be used successfully in postoperative parotid surgery. The aim of this article was to demonstrate the efficiency of postoperative use of scopolamine transdermal patch in reduction of complications due to the presence of saliva in the surgical spaces.

Botulinum Toxin A for Oral Cavity Cancer Patients: In Microsurgical Patients BTX Injections in Major Salivary Glands Temporarily Reduce Salivary Production and the Risk of Local Complications Related to Saliva Stagnation

In patients suffering from oral cavity cancer surgical treatment is complex because it is necessary to remove carcinoma and lymph node metastasis (through a radical unilateral or bilateral neck dissection) and to reconstruct the affected area by means of free flaps. The saliva stagnation in the post-operative period is a risk factor with regard to local complications. Minor complications related to saliva stagnation (such as tissue maceration and wound dehiscence) could become major complications compromising the surgery or the reconstructive outcome. In fact the formation of oro-cutaneous fistula may cause infection, failure of the free flap, or the patient’s death with carotid blow-out syndrome. Botulinum injections in the major salivary glands, four days before surgery, temporarily reduces salivation during the healing stage and thus could reduce the incidence of saliva-related complications. Forty three patients with oral cancer were treated with botulinum toxin A. The saliva quantitative measurement and the sialoscintigraphy were performed before and after infiltrations of botulinum toxin in the major salivary glands. In all cases there was a considerable, but temporary, reduction of salivary secretion. A lower rate of local complications was observed in the post-operative period. The salivary production returned to normal within two months, with minimal side effects and discomfort for the patients. The temporary inhibition of salivary secretion in the post-operative period could enable a reduction in saliva-related local complications, in the incidence of oro-cutaneous fistulas, and improve the outcome of the surgery as well as the quality of residual life in these patients.

Comparison of salivary calmodulin binding proteins in Sjögren's syndrome and healthy individuals

Reduction in salivary secretion is the hallmark of Sjögren's syndrome (SS). Calmodulin (CaM) and calmodulin binding proteins (CaMBPs) play a key role in the secretory process of saliva. Recent studies have suggested that SS-B, an autoantibody associated with SS, is a CaMBP. This finding suggests that CaMBP may contribute to the loss of saliva in SS. To better understand the role(s) of these proteins in SS, the purpose of this study was to compare salivary CaMBPs in Sjögren's patients and controls. Saliva samples were collected from 20 patients and 20 age-, race-, and gender-matched controls. CaM overlay was used to identify CaMBPs in saliva of patients and controls. Higher number of salivary CaMBPs was observed among patients than controls. The increased number of salivary CaMBPs in SS may suggest a potential role for these proteins in the pathogenesis of the disease.

Parasympathetic innervation of the salivary glands

The autonomic nervous system (ANS) is a mixed nervous system. There are two divisions of the ANS: the parasympathetic autonomous nervous system (PANS), and the sympathetic autonomic nervous system (SANS). The PANS plays a role in the conservation and homeostasis of bodily functions. The cells giving rise to parasympathetic fibers are situated at three different levels of the central nervous system: the midbrain, the medulla oblongata, and the sacral region of the spinal cord. The parasympathetic fibers leave the brain in the facial (VII CN), glossopharyngeal (IX CN), and vagus (X CN) nerves. The postganglionic parasympathetic fibers of the VII CN enter the sublingual and submanidublar glands and the minor salivary glands of the mucous membrane of the mouth, pharynx and nasopharynx, and those of the IX CN converge into the parotid gland. Parasympathetic postganglionic cholinergic nerve fibers supply cells of both the secretory end-piece and ducts and stimulate the rate of salivary secretion, inducing the formation of large amounts of a low-protein, serous saliva. Parasympathetic denervation of the major salivary glands leads to an immediate reduction of salivary secretion.