Integrated therapy of intraductal irrigations and sialoendoscopies of salivary glands to improve mouth dryness.

OBJECTIVE: To assess the combination of salivary gland intraductal irrigations (IG) followed by sialoendoscopy irrigations (SI) of the parotid gland on the improvement of salivary gland secretory dysfunction (SGSD). METHODS: We retrospectively analyzed the records of SGSD patients who underwent major salivary gland IG followed by SI during 2014-2020. Records included demographics, systemic background, signs, and symptoms. Improvement was assessed by comparing the mean unstimulated and stimulated whole salivary flow rate (UWSF, SWSF) from the baseline point (before IG procedure) to the last point (after SI) using repeated measures. The between-subjects effects of various factors and covariants were analyzed using repeated measures ANCOVA. RESULTS: One hundred patients were included with an age range of 15-83 years (mean age of 60.1 ± 13.1 years). Improvement was detected on UWSF measurements (p = 0.031, F = 3.83), but not on SWSF measurements (p = 0.165, F = 1.85). The between-subjects effects on UWSF measurements were statistically significant for sex (p = 0.003, F = 9.526) and salivary gland manipulators use (p < 0.001, F = 15.107) and for the interaction between sex and salivary gland manipulators use (p- = 0.002, F = 9.709). Results of long-term follow-up for 10.87 ± 11.79 months after the SI procedure demonstrated sustained improvement in UWSF measurements (p = 0.011, F = 4.91). CONCLUSIONS: The combination of IG followed by SI increases UWSF salivary secretion in SGSD patients for a relatively extended duration.

Prosthodontic implications of saliva and salivary gland dysfunction.

PURPOSE: To provide a detailed overview of the fundamentals of saliva constituents and production. The review outlines the clinical manifestations as a consequence of salivary gland dysfunction and management strategies for patients with salivary gland dysfunction. Prosthodontic implications of saliva and salivary gland dysfunction are presented. MATERIALS AND METHODS: English-language literature relating to saliva constituents, physiologic saliva production, clinical manifestations secondary to salivary gland dysfunction, salivary biomarkers, and management strategies were retrieved via electronic search. Relevant articles were summarized for this manuscript with a view toward providing pragmatic information. RESULTS: Saliva is produced by three pairs of major and minor salivary glands. The major salivary glands, namely, the parotid, submandibular, and sublingual glands, contribute approximately 90% of saliva production. Saliva contains serous and mucinous secretions produced by different types of cells within salivary glands. Parasympathetic and sympathetic fibers innervate the major salivary glands, and upon stimulation, the parasympathetic innervation increases serous secretions, while the sympathetic innervation increases protein secretion. Stimulated saliva is mainly derived from the parotid glands which are composed of serous acini, while unstimulated saliva is mainly derived from the submandibular glands which are composed of mixed seromucous acini. As major salivary glands contribute the most to salivary flow, local or systemic factors influencing those glands can disrupt saliva production resulting in clinically significant oral manifestations. CONCLUSION: This review provides a fundamental overview of saliva production. In addition, the review highlights the various clinical manifestations secondary to salivary gland dysfunction, explores salivary biomarkers for screening of systemic diseases, discusses management strategies for patients with salivary gland dysfunction, and outlines the prosthodontic implications of saliva and salivary gland dysfunction.

Normal salivary production using a swab method in clinical settings.

OBJECTIVES: The purpose of the study was to generate age- and gender-based normative data for unstimulated salivary flow rate (uSFR) by means of a swab method, and to provide preliminary results of using the test in patients suspected of reduced salivary function. METHODS: The 130 healthy participants without subjective xerostomia or suspicion of reduced salivation were recruited. Measurements of uSFR were conducted three times per subject and mean uSFR was calculated for the entire population and stratified according to age and gender. The method was applied in a pilot population of 25 patients suffering from either Sjögren's syndrome or had underwent irradiation of the head and neck. RESULTS: Mean uSFR in the healthy group was 0.808 g/min (range: 0.165-2.442). Not significant trends towards declining uSFR with increasing age and higher uSFR in women were seen. Mean uSFR in the patients was 0.429 g/min (range: 0.111-1.448), which was significantly lower than normative values. Use of xerogenic drugs correlated to lower uSFR. CONCLUSION: Age- and gender-based normative data of uSFR was presented using a fast and readily implementable swab test. The test was able to objectively verify hyposalivation among patients suffering from Sjögren's syndrome or having been exposed to head and neck radiation.

Choline Acetyltransferase Induces the Functional Regeneration of the Salivary Gland in Aging SAMP1/Kl -/- Mice.

Salivary gland dysfunction induces salivary flow reduction and a dry mouth, and commonly involves oral dysfunction, tooth structure deterioration, and infection through reduced salivation. This study aimed to investigate the impact of aging on the salivary gland by a metabolomics approach in an extensive aging mouse model, SAMP1/Klotho -/- mice. We found that the salivary secretion of SAMP1/Klotho -/- mice was dramatically decreased compared with that of SAMP1/Klotho WT (+/+) mice. Metabolomics profiling analysis showed that the level of acetylcholine was significantly decreased in SAMP1/Klotho -/- mice, although the corresponding levels of acetylcholine precursors, acetyl-CoA and choline, increased. Interestingly, the mRNA and protein expression of choline acetyltransferase (ChAT), which is responsible for catalyzing acetylcholine synthesis, was significantly decreased in SAMP1/Klotho -/- mice. The overexpression of ChAT induced the expression of salivary gland functional markers (α-amylase, ZO-1, and Aqua5) in primary cultured salivary gland cells from SAMP1/Klotho +/+ and -/- mice. In an in vivo study, adeno-associated virus (AAV)-ChAT transduction significantly increased saliva secretion compared with the control in SAMP1/Klotho -/- mice. These results suggest that the dysfunction in acetylcholine biosynthesis induced by ChAT reduction may cause impaired salivary gland function.

Diffusion-weighted imaging as a follow-up modality for evaluation of major salivary gland function in nasopharyngeal carcinoma patients: a preliminary study.

PURPOSE: To investigate the value of diffusion-weighted imaging (DWI) in assessing dynamic changes of major salivary gland function during follow-up post radiotherapy (RT) in nasopharyngeal carcinoma (NPC) patients. MATERIALS AND METHODS: 31 consecutive patients with pathologically confirmed NPC scheduled for RT underwent six routine follow-up MRI examinations including DWI sequence prior to (pre-RT) and 1, 3, 6, 9, and 12 months post RT. Mean apparent diffusion coefficient (ADC) values of bilateral parotid glands (PGs) and submandibular glands (SMGs) were measured. Objective measurement of salivary flow rate (SFR) under unstimulated (uSFR) and stimulated conditions (sSFR) as well as subjective xerostomia assessment according to a patient-rated questionnaire were conducted before each MRI. Variance analysis was used to evaluate dynamic changes of ADC, SFR and xerostomia questionnaire summary scores (XQ-sum) at different timepoints and the correlation between ADC and XQ-sum. Pearson's correlation test was used to evaluate the correlations between pre- and post-RT changes of ADC (ΔADC) and SFR (ΔSFR) or mean RT dose. RESULTS: At each timepoint, ADCs of PGs were significantly lower than of SMGs, uSFR was significantly lower than sSFR. For both PGs and SMGs, ADCpost-RT were all higher than ADCpre-RT, with significant differences. ADC1m-post-RT initially increased and changed little to ADC3m-post-RT, ADC6m-post-RT, ADC9m-post-RT, and ADC12m-post-RT, then gradually declined over time. The dynamic change trends of SFR were negatively paralleled to those of ADC, while that of XQ-sum was similar. Dose-response relationships were detected between salivary gland mean RT dose and ΔADC. In PGs, negative correlations between ΔsSFR9m-post-RT and ΔADC9m-post-RT, and ΔsSFR12m-post-RT and ΔADC12m-post-RT were detected. In SMGs, negative correlations between ΔsSFR12m-post-RT and ΔADC12m-post-RT, and ΔuSFR12m-post-RT and ΔADC12m-post-RT were also detected. The ADCs of patients with severe subjective xerostomia were significantly higher, while patients with moderate subjective xerostomia presented a tendency toward higher ADCs compared to those with mild xerostomia from 6 to 12 months post RT. CONCLUSION: As part of routine follow-up MRI in NPC patients, DWI might be a promising modality for follow-up assessing the dynamic changes of major salivary gland function and might be more powerful in the late post-RT period.

Improvement of dry mouth following intraductal irrigation of salivary glands.

OBJECTIVES: To assess the effect of major salivary gland intraductal irrigations (IGs) to relieve mouth dryness. METHODS: We retrospectively analyzed the records of patients with mouth dryness who underwent major salivary gland IG during 2013-2015. Records included demographics, medical background, dry mouth etiologies and symptomatology, and results of sialometry and sialo-cone-beam computerized tomography. Subjective improvement following the IG procedure (yes/no) and sustained subjective improvement (mouth dryness relief for ≥1 month) were recorded. Objective improvement was assessed by comparing the mean unstimulated (USF) and stimulated (SSF) whole salivary flow (WSF) rate before and after the IG. RESULTS: Seventy-four patients were included [mean age: 59.08 ± 12.46 years]. Improvement was detected in the USF (p = .027), but not in the SSF (p = .878). Fifty-five (84.6%) noted subjective improvement, while 10 (15.4%) did not. Subjective improvement was positively associated with the USF following IG (p = .037), with salivary gland swelling episodes (p = .033), and with difficulties in swallowing dry foods (p = .014). Of those with subjective improvement, 45 (81.8%) reported sustained improvement, which was positively associated with lack of a gritty eye sensation (p = .042) and abnormal sialo-CBCT findings (p = .001). CONCLUSIONS: Major salivary gland IG is a simple and safe procedure that may relieve dry mouth for a relatively extended duration. Further studies are needed to confirm these preliminary findings and assess their underlying mechanisms.

Current cell models for bioengineering a salivary gland: a mini-review of emerging technologies.

Oral Diseases (2013) 19, 236-244 Saliva plays a major role in maintaining oral health. Patients afflicted with a decrease in saliva secretion (symptomatically, xerostomia) exhibit difficulty in chewing and swallowing foods, tooth decay, periodontal disease, and microbial infections. Despite recent improvements in treating xerostomia (e.g., saliva stimulants, saliva substitutes, and gene therapy), there is a need of more scientific advancements that can be clinically applied toward restoration of compromised salivary gland function. Here we provide a summary of the current salivary cell models that have been used to advance restorative treatments via development of an artificial salivary gland. These models represent initial steps toward clinical and translational research, to facilitate creation of clinically safe salivary glands. Further studies in salivary cell lines and primary cells are necessary to improve survival rates, cell differentiation, and secretory function. Additionally, the characterization of salivary progenitor and stem cell markers are necessary. Although these models are not fully characterized, their improvement may lead to the construction of an artificial salivary gland that is in high demand for improving the quality of life of many patients suffering from salivary secretory dysfunction.

Association Between Salivary Cytokines, Chemokines and Growth Factors and Salivary Gland Function in Children with Chronic Kidney Disease.

Introduction: Chronic kidney disease (CKD) is a systemic inflammatory disease that leads to multiple organ complications not only in the kidneys and the cardiovascular system, but also in the oral cavity. CKD children experience reduced saliva secretion (hyposalivation), which leads to increased incidence of dental caries and significant impairment of patients' quality of life. However, the causes of salivary gland dysfunction in children with CKD are unknown. The present study is the first to evaluate the inflammatory and anti-inflammatory profile in the saliva of children with CKD at different stages of renal failure with normal and reduced salivary gland function. Methods: Thirty children with CKD (age 9-16) and thirty age- and gender-matched healthy children were classified for the study. Salivary inflammatory and anti-inflammatory profile were assayed using the multiplex ELISA assay. Results: We demonstrated statistically significant changes in salivary pro-inflammatory (↑TNF-α, ↓IL-7), anti-inflammatory (↑IL-10), Th1 (↑INF-γ, ↑IL-15), Th2 (↑IL-4, ↑IL-5, ↑IL-6, ↑IL-9) and Th17 (IL-17) cytokines as well as chemokines (↑MCP-1/CCL-2, ↑MIP-1α/CCL3, ↓MIP-1ß/CCL4, ↓EOTAXIN/CCL11) and growth factors (↑G-CSF, ↑FGF) in unstimulated saliva of children with CKD compared to the controls. Although the evaluation of the salivary inflammatory profile does not indicate a particular dominance of any of the branches of the immune system, we observed a statistically significant increase in the concentration of all Th2 cytokines assayed. The multivariate regression analysis showed that the content of salivary cytokines, chemokines and growth factors depends on the secretory function of the salivary glands, ie, salivary flow, total protein concentration and amylase activity in the saliva. Salivary MIP-1α/CCL3 was the most effective to differentiate children with CKD and hyposalivation from patients with normal saliva secretion. Discussion: Inflammation is involved in salivary gland dysfunction in children with CKD, although further studies on in vitro and in vivo models are necessary to confirm this hypothesis.

Oral Complications from Oropharyngeal Cancer Therapy.

Post-oropharyngeal cancer treatment complications include a multitude of oral side effects that impact overall survival and quality of life. These include acute and chronic conditions affecting the oral cavity and head and neck, such as mucositis, infection, xerostomia, dysgeusia, radiation caries, osteonecrosis, and trismus. This review will summarize the most common oral complications from oropharyngeal cancer therapy. The authors would like to point out that the literature cited frequently combines oropharyngeal and head and neck cancer results. If recommendations are made strictly related to oropharyngeal cancers, this will be highlighted.

Metformin-induced activation of Ca2+ signaling prevents immune infiltration/pathology in Sjogren's syndrome-prone mouse models.

Immune cell infiltration and glandular dysfunction are the hallmarks of autoimmune diseases such as primary Sjogren's syndrome (pSS), however, the mechanism(s) is unknown. Our data show that metformin-treatment induces Ca2+ signaling that restores saliva secretion and prevents immune cell infiltration in the salivary glands of IL14α-transgenic mice (IL14α), which is a model for pSS. Mechanistically, we show that loss of Ca2+ signaling is a major contributing factor, which is restored by metformin treatment, in IL14α mice. Furthermore, the loss of Ca2+ signaling leads to ER stress in salivary glands. Finally, restoration of metformin-induced Ca2+ signaling inhibited the release of alarmins and prevented the activation of ER stress that was essential for immune cell infiltration. These results suggest that loss of metformin-mediated activation of Ca2+ signaling prevents ER stress, which inhibited the release of alarmins that induces immune cell infiltration leading to salivary gland dysfunction observed in pSS.

Targeting alarmin release reverses Sjogren's syndrome phenotype by revitalizing Ca2+ signalling.

BACKGROUND: Primary Sjogren's syndrome (pSS) is a systemic autoimmune disease that is embodied by the loss of salivary gland function and immune cell infiltration, but the mechanism(s) are still unknown. The aim of this study was to understand the mechanisms and identify key factors that leads to the development and progression of pSS. METHODS: Immunohistochemistry staining, FACS analysis and cytokine levels were used to detect immune cells infiltration and activation in salivary glands. RNA sequencing was performed to identify the molecular mechanisms involved in the development of pSS. The function assays include in vivo saliva collection along with calcium imaging and electrophysiology on isolated salivary gland cells in mice models of pSS. Western blotting, real-time PCR, alarmin release, and immunohistochemistry was performed to identify the channels involved in salivary function in pSS. RESULTS: We provide evidence that loss of Ca2+ signaling precedes a decrease in saliva secretion and/or immune cell infiltration in IL14α, a mouse model for pSS. We also showed that Ca2+ homeostasis was mediated by transient receptor potential canonical-1 (TRPC1) channels and inhibition of TRPC1, resulting in the loss of salivary acinar cells, which promoted alarmin release essential for immune cell infiltration/release of pro-inflammatory cytokines. In addition, both IL14α and samples from human pSS patients showed a decrease in TRPC1 expression and increased acinar cell death. Finally, paquinimod treatment in IL14α restored Ca2+ homeostasis that inhibited alarmin release thereby reverting the pSS phenotype. CONCLUSIONS: These results indicate that loss of Ca2+ signaling is one of the initial factors, which induces loss of salivary gland function along with immune infiltration that exaggerates pSS. Importantly, restoration of Ca2+ signaling upon paquinimod treatment reversed the pSS phenotype thereby inhibiting the progressive development of pSS.

Hyposalivation and Xerostomia and Burning Mouth Syndrome: Medical Management.

In this chapter, the authors review the benefits of saliva and the destructive consequences of its loss. It is hoped that this will help their colleagues identify and treat patients before development of symptoms. Xerostomia is the subjective complaint of dry mouth or sensation of oral dryness. Hyposalivation is the actual decrease in measured salivary outflow. The authors discuss a compiled list of highly cited medications commonly used today that are linked with xerostomia and hyposalivation. There are numerous treatment modalities that are present, such as saliva substitutes, mouth rinses, sugar-free candy, and pilocarpine among others.

Age-dependent oral manifestations of neurofibromatosis type 1: a case-control study.

INTRODUCTION: Most craniofacial manifestations of neurofibromatosis type 1 (NF1) are considered as a result of tumor compression. We sought to determine salivary changes, caries, and periodontal complications in NF1 patients without tumors in the oral cavity. OBJECTIVE AND METHODS: Eleven NF1 patients without tumors in the oral cavity and 29 matched controls without NF1 were enrolled in this case-control study. Demographic information, medical history, and data of intraoral examinations, including the Decayed, Missing, and Filled Teeth (DMFT) scores and Russel's periodontal index (PI), were recorded. The functional salivary analysis was performed for sialometry, salivary pH values, and amylase activity. Ingenuity Systems Pathway Analysis (IPA) was conducted to identify mutually activated pathways for NF1-associated oral complications. RESULTS: NF1 patients were associated with periodontitis (OR = 1.40, 95% CI = 1.06-1.73, P = 0.04), gingivitis (OR = 1.55, 95% CI = 1.09-2.01, P = 0.0002), and decreased salivary flow rates (OR = 1.40, 95% CI = 1.05-1.76, P = 0.005). Periodontal destruction, salivary changes, and dental caries in NF1 patients were age-dependent. Subgroup analyses based on age stratification suggested that salivary flow rates and salivary amylase activities were significantly low in NF1 patients aged over 20 years and that salivary pH values, PI and DMFT scores were significantly high among NF1- controls aged over 20. All oral complications were not significantly presented in NF1 patients aged below 20 years. IPA analyses suggested that cellular mechanisms underlying NF1-associated oral complications involved chronic inflammatory pathways and fibrosis signaling pathway. CONCLUSION: NF1 patients without tumors in the oral cavity presented a comparatively high prevalence of age-dependent oral complications, including periodontal destruction and salivary gland dysfunction, which were associated with chronic inflammatory pathogenesis.

Assessment of salivary gland function after 177Lu-PSMA radioligand therapy: Current concepts in imaging and management.

Prostate specific membrane antigen (PSMA) is a transmembrane protein that is highly expressed on prostate epithelial cells and is strongly upregulated in prostate cancer. Radioligand therapy using beta-emitting Lutetium-177 (177Lu)-labeled-PSMA-617, a radiolabeled small molecule, has gained attention as a novel targeted therapy for metastatic prostate cancer, given its high affinity and long tumor retention, and rapid blood pool clearance. In March 2022, the United States Food and Drug administration has granted approval to the targeted 177Lu-PSMA-617 therapy for treatment of patients with PSMA-positive metastatic castration resistant prostate cancer, who have been previously treated with an androgen-receptor pathway inhibitor and taxane-based chemotherapy. Studies have demonstrated the adverse effects of this treatment, mainly encountered due to radiation exposure to non-target tissues. Salivary glands show high PSMA-ligand uptake and receive increased radiation dose secondary to accumulation of 177Lu-PSMA-617. This predisposes the glands to radiation-mediated toxicity. The exact mechanism, scope and severity of radiation-mediated salivary gland toxicity are not well understood, however, the strategies for its prevention and treatment are under evaluation. This review will focus on the current knowledge about salivary gland impairment post 177Lu labeled PSMA-based radioligand therapies, diagnostic methodologies, and imaging with emphasis on salivary gland scintigraphy. The preventive strategies and known treatment options would also be briefly highlighted.

Prevalence and Risk Factors for Hyposalivation and Xerostomia in Childhood Cancer Survivors Following Different Treatment Modalities-A Dutch Childhood Cancer Survivor Study Late Effects 2 Clinical Study (DCCSS LATER 2).

Background: Limited data are available on the risk factors of salivary gland dysfunction in long-term childhood cancer survivors (CCS). The objective of this cross-sectional study, part of the multidisciplinary multicenter Dutch CCS Study Late Effects 2 (DCCSS LATER 2), was to assess the prevalence of and risk factors for hyposalivation and xerostomia in CCS. Methods: From February 2016 until March 2020, 292 CCS were included. Data with regard to gender, age at study, diagnosis, age at diagnosis, and treatment characteristics were collected, as well as the unstimulated (UWS) and stimulated whole salivary flow rate (SWS). Xerostomia was assessed with the Xerostomia Inventory (XI) questionnaire. Multivariable Poisson regression analyses were used to evaluate the association between potential risk factors and the occurrence of hyposalivation. Results: The minimum time between diagnosis and study enrollment was 15 years. The prevalence of hyposalivation was 32% and the prevalence of xerostomia was 9.4%. Hyposalivation and xerostomia were not significantly correlated. Risk factors for hyposalivation were female gender and a higher dose of radiotherapy (>12 Gy) to the salivary gland region. Conclusion: Considering the importance of saliva for oral health, screening for hyposalivation in CCS is suggested in order to provide optimal oral supportive care aimed to improve oral health.

Salivary Gland Dysfunction in Patients with Chronic Heart Failure Is Aggravated by Nitrosative Stress, as Well as Oxidation and Glycation of Proteins.

Chronic heart failure (HF) is an important clinical, social, and economic problem. A key role in HF progression is played by oxidative stress. Free oxygen radicals, formed under the conditions of hypoxia and reperfusion, participate in myocardial stunning and other forms of post-reperfusion damage. HF patients also suffer from disorders connected with saliva secretion. However, still little is known about the mechanisms that impair the secretory function of salivary glands in these patients. In the presented study, we were the first to compare the antioxidant barrier, protein glycoxidation, and nitrosative/nitrative stress in non-stimulated (non-stimulated whole saliva (NWS)) and stimulated (SWS) saliva of HF patients. The study included 50 HF patients with normal saliva (NS) secretion (n = 27) and hyposalivation (HS) (n = 23), as well as an age- and gender-matched control group (n = 50). We demonstrated that, in NWS of HF patients with HS, the concentration of low-molecular-weight non-enzymatic antioxidants decreased (↓total polyphenols, ↓ascorbic acid, ↓reduced glutathione, ↓albumin) compared to HF patients with normal saliva (NS) secretion, as well as the control group (except albumin). We also observed increased content of protein glycoxidation products (↑dityrosine, ↑kynurenine, ↑glycophore) in NWS and SWS of HF patients with HS compared to healthy controls. Interestingly, the content of dityrosine, N-formylkynurenine, and glycophore in NWS was also significantly higher in HF patients with HS compared to those with NS secretion. The concentration of NO was considerably lower, while the levels of peroxynitrite and nitrotyrosine were significantly higher in NWS and SWS of HF subjects with HS compared to the controls. Salivary gland dysfunction occurs in patients with chronic HF with the submandibular salivary glands being the least efficient. Oxidative/nitrosative stress may be one of the mechanisms responsible for the impairment of salivary gland secretory function in HF patients.

A pretest-posttest pilot study for the development and preliminary validation of a tool for the clinical assessment of radioiodine induced sialadenitis.

OBJECTIVES: The clinical assessment of radioiodine-induced sialadenitis is relied on the observer-defined toxicity grading model. However, this model has significant limitations, the major one being the lack of systematic assessment based on objective criteria. The main aim of this study was the development and testing of an assessment tool which could examine the severity of post-irradiation sialadenitis. METHODS: The development of the Sialadenitis Assessment Tool proceeded through three phases. The first and second phases included a literature review and the development of the tool which derived from the review, respectively. The third phase involved a pilot testing of the Assessment Tool to a sample of 34 patients undergoing I131 therapy. The assessment was carried out by two independent healthcare professionals, pre- and post-radioiodine therapy. The results of the assessment tool were compared with other scales, including the DIRIX and EORTC H&N35. RESULTS: According to the Cohen's kappa test, the Sialadenitis Assessment Tool is a reliable tool for the assessment of sialadenitis (Cohen's κ = 1). The concurrent and internal validity tests showed a tendency of association with most variables (p < 0.001) in the DIRIX and EORTC QLQ-HN35 scales. CONCLUSION: Preliminary evidence show that Sialadenitis Assessment Tool is a valid and reliable tool to assess radioiodine-induced sialadenitis in patients undergoing I131 therapy post-thyroidectomy.

Salivary exosomes as a new therapy to ameliorate diabetes mellitus and combat xerostomia and submandibular salivary glands dysfunction in diabetic rats.

Diabetes mellitus (DM) is one of the major metabolic diseases. Xerostomia and salivary gland dysfunction are of its common oral complications. Exosomes, as a new therapeutic potential containing nucleic acids, proteins and lipids, act as effective vehicles for target molecules delivery. Accordingly, their therapeutic use is gaining much interest. Therefore, this work aimed to assess the therapeutic efficacy of salivary exosomes in ameliorating DM and combating xerostomia as a complication of salivary gland dysfunction in diabetic rats. In the current study, salivary exosomes were injected intravenously to rats of group II (Salivary Exo-treated group) one week after diabetes induction. Group I (Diabetic group) was left untreated. Blood sugar level was checked weekly. Water intake, salivary flow rate, salivary amylase and serum nitric oxide were assessed before and after diabetes induction and at the end of the study. After 5 weeks from the beginning of the study, salivary gland tissues were dissected and examined histologically and ultrastructurally. Gene expression of the inflammatory markers NFκB/p65 and TNFα was assessed by polymerase chain reaction. The results showed that salivary exosomes reduced blood glucose levels and enhanced salivary glands' function. This was indicated by a decrease in water intake, salivary amylase and serum nitric oxide in addition to an increase in salivary flow rate. This was confirmed histologically, ultrastructurally and via downregulation of NFκB/p65 and TNFα gene expression. Our results concluded that salivary exosomes could be considered as a novel cell free based therapy in treatment of xerostomia and salivary gland dysfunction in DM.

Research status and prospects of acupuncture for prevention and treatment of chemo- and radiotherapy-induced salivary gland dysfunction in head and neck cancer.

Salivary gland dysfunction (SGD) induced by chemo- and radiotherapy for head and neck cancer (HNC) has always been a difficult problem in modern medicine. The quality of life of a large number of HNC patients is severely impaired by SGD such as xerostomia and dysphagia. In recent years, several studies have found that acupuncture can improve patients' salivary secretion, but it has not yet been approved as an alternative therapy for SGD. For this reason, we collected the clinical study reports on acupuncture in the treatment of SGD induced by chemo- and radiotherapy in HNC patients in the past 20 years, and analyzed and discussed the advantages and disadvantages of these studies with respect to tumor types, group setting, intervention modality, acupoints selection, outcome evaluation, and safety. We believed that acupuncture is beneficial for SGD, but the existing objective evidence is insufficient to support its effectiveness. Therefore, improving the Standards for Reporting Interventions in Clinical Trials of Acupuncture, selecting the optimal combination of acupoints through scientific and rigorous study design, and exploring the potential mechanism of acupuncture in the treatment of diseases combined with the meridian theory may be effective ways to promote the acceptance of acupuncture as an alternative therapy for SGD in future. The significance of this review is to provide a reference for researchers to carry out high-quality clinical trials of acupuncture in the treatment of SGD in future from the perspective of the combination of modern medicine and traditional Chinese medicine.

Salivary Gland Dysfunction, Protein Glycooxidation and Nitrosative Stress in Children with Chronic Kidney Disease.

This study is the first to evaluate protein glycooxidation products, lipid oxidative damage and nitrosative stress in non-stimulated (NWS) and stimulated whole saliva (SWS) of children with chronic kidney disease (CKD) divided into two subgroups: normal salivary secretion (n = 18) and hyposalivation (NWS flow < 0.2 mL min-1; n = 12). Hyposalivation was observed in all patients with severe renal failure (4-5 stage CKD), while saliva secretion > 0.2 mL/min in children with mild-moderate CKD (1-3 stage) and controls. Salivary amylase activity and total protein content were significantly lower in CKD children with hyposalivation compared to CKD patients with normal saliva secretion and control group. The fluorescence of protein glycooxidation products (kynurenine, N-formylkynurenine, advanced glycation end products), the content of oxidative damage to lipids (4-hydroxynonneal, 8-isoprostanes) and nitrosative stress (peroxynitrite, nitrotyrosine) were significantly higher in NWS, SWS, and plasma of CKD children with hyposalivation compared to patients with normal salivary secretion and healthy controls. In CKD group, salivary oxidation products correlated negatively with salivary flow rate, -amylase activity and total protein content; however, salivary oxidation products do not reflect their plasma level. In conclusion, children with CKD suffer from salivary gland dysfunction. Oxidation of salivary proteins and lipids increases with CKD progression and deterioration of salivary gland function.