Salivary Gland Function Research Articles

Abstract IA-020: Optimizing stem cell niche for post-irradiation regeneration

Abstract Radiotherapy involves unavoidable co-irradiation of the normal tissue, often resulting in side effects that limit the dose to the tumor and/or reduce quality of life of cancer survivors. The response of normal tissues to irradiation is mainly determined by the survival and regenerative potential of the tissue stem cells, and modulated by inflammatory processes, vasculature damage, altered neuronal innervation and fibrosis. Indeed, transplantation of tissue specific stem cells has been shown to restores tissue homeostasis and prevent late radiation effects. However, the radiation-induced senescence, fibrosis, and chronic inflammation may chance the stem cell niche engender an unfavorable environment for the regenerative potential of the tissue’s stem cells. Here changes in the salivary gland stem cell niche will be discussed using irradiated murine submandibular salivary gland tissue and derived organoids. Recently, we have developed methods to culture murine and patient specific tissue resembling salivary gland organoids (SGO). SGO contain all the glandular lineages, are able to extensively self-renew and up on transplantation rescue salivary gland function, allowing the study of radiation responses. The role of stemness factors, senescence and inflammatory processes in stem cell self-renewal and differentiation and post-irradiation regeneration will be discussed. Using SGO formation efficiency (OFE) as a measure of regenerative potential it is shown that stem cell potency after in vivo irradiation, is time dependent reduced. Interestingly, the conditioned medium of irradiated SGO reduced the OFE of unirradiated SGO. The potential role of radiation-induced senescence-associated secretory phenotype, hippo-signaling and inflammation through activation of cytosolic DNA sensing pathways on stem cells function will be addressed. Radiation-induced environmental changes in the stem cells niche have a severe impact on stem cell function. Modulation of these effect may enhance regenerative potential of surviving stem cells and improve engraftment and regeneration after stem cell transplantation. Supported by the Dutch Cancer Society (KWF, grant No. 10650 and 12092) and The Netherlands Organisation for Health Research and Development (ZonMw, Grant nrs. 11.600.1023 and 40-43600-98-14003). Citation Format: Rob P. Coppes. Optimizing stem cell niche for post-irradiation regeneration [abstract]. In: Proceedings of the AACR Virtual Special Conference on Radiation Science and Medicine; 2021 Mar 2-3. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(8_Suppl):Abstract nr IA-020.

Quantitative salivary gland SPECT/CT using deep convolutional neural networks

Quantitative single-photon emission computed tomography/computed tomography (SPECT/CT) using Tc-99m pertechnetate aids in evaluating salivary gland function. However, gland segmentation and quantitation of gland uptake is challenging. We develop a salivary gland SPECT/CT with automated segmentation using a deep convolutional neural network (CNN). The protocol comprises SPECT/CT at 20 min, sialagogue stimulation, and SPECT at 40 min post-injection of Tc-99m pertechnetate (555 MBq). The 40-min SPECT was reconstructed using the 20-min CT after misregistration correction. Manual salivary gland segmentation for %injected dose (%ID) by human experts proved highly reproducible, but took 15 min per scan. An automatic salivary segmentation method was developed using a modified 3D U-Net for end-to-end learning from the human experts (n = 333). The automatic segmentation performed comparably with human experts in voxel-wise comparison (mean Dice similarity coefficient of 0.81 for parotid and 0.79 for submandibular, respectively) and gland %ID correlation (R2 = 0.93 parotid, R2 = 0.95 submandibular) with an operating time less than 1 min. The algorithm generated results that were comparable to the reference data. In conclusion, with the aid of a CNN, we developed a quantitative salivary gland SPECT/CT protocol feasible for clinical applications. The method saves analysis time and manual effort while reducing patients’ radiation exposure.

Mitochondria-targeted antioxidant protects against irradiation-induced salivary gland hypofunction

A severe consequence of radiation therapy in patients with head and neck cancer is persistent salivary gland hypofunction which causes xerostomia and oral infections. We previously showed that irradiation (IR) of salivary glands in mice triggers initial transient increases in mitochondrial reactive oxygen species (ROSmt), mitochondrial [Ca2+] ([Ca2+]mt), and activated caspase-3 in acinar cells. In contrast, loss of salivary secretion is persistent. Herein we assessed the role of ROSmt in radiation-induced irreversible loss of salivary gland function. We report that treatment of mice with the mitochondrial-targeted antioxidant, MitoTEMPO, resulted in almost complete protection of salivary gland secretion following either single (15 Gy) or fractionated (5 × 3 Gy) doses of irradiation. Salivary gland cells isolated from MitoTEMPO-treated, irradiated, mice displayed significant attenuation of the initial increases in ROSmt, ([Ca2+]mt, and activated caspase-3 as compared to cells from irradiated, but untreated, animals. Importantly, MitoTEMPO treatment prevented radiation-induced decrease in STIM1, consequently protecting store-operated Ca2+ entry which is critical for saliva secretion. Together, these findings identify the initial increase in ROSmt, that is induced by irradiation, as a critical driver of persistent salivary gland hypofunction. We suggest that the mitochondrially targeted antioxidant, MitoTEMPO, can be potentially important in preventing IR-induced salivary gland dysfunction.

Environmental Cadmium Exposure and Dental Indices in Orthodontic Patients.

Background. Previous studies have shown that environmental cadmium exposure could disrupt salivary gland function and is associated with dental caries and reduced bone density. Therefore, this cross-sectional study attempted to determine whether tooth decay with tooth loss following cadmium exposure is associated with some dental or skeletal traits such as malocclusions, sagittal skeletal pattern, and tooth decay. Methods. Between August 2019 and June 2020, 60 orthodontic patients with no history of previous orthodontics, functional appliances, or surgical treatment were examined. The patients were stratified into two groups according to their urine cadmium concentrations: high (>1.06 µg/g creatinine, n = 28) or low (<1.06 µg/g creatinine, n = 32). Results. The patients were 25.07 ± 4.33 years old, and most were female (female/male: 51/9 or 85%). The skeletal relationship was mainly Class I (48.3%), followed by Class II (35.0%) and Class III (16.7%). Class I molar relationships were found in 46.7% of these patients, Class II molar relationships were found in 15%, and Class III molar relationships were found in 38.3%. The mean decayed, missing, and filled surface (DMFS) score was 8.05 ± 5.54, including 2.03 ± 3.11 for the decayed index, 0.58 ± 1.17 for the missing index, and 5.52 ± 3.92 for the filled index. The mean index of complexity outcome and need (ICON) score was 53.35 ± 9.01. The facial patterns of these patients were within the average low margin (26.65 ± 5.53 for Frankfort–mandibular plane angle (FMA)). There were no significant differences in the above-mentioned dental indices between patients with high urine cadmium concentrations and those with low urine cadmium concentrations. Patients were further stratified into low (<27, n = 34), average (27–34, n = 23), and high (>34, n = 3) FMA groups. There were no statistically significant differences in the urine cadmium concentration among the three groups. Nevertheless, a marginally significant p-value of 0.05 for urine cadmium concentration was noted between patients with low FMA and patients with high FMA. Conclusion. This analysis found no association between environmental cadmium exposure and dental indices in our orthodontic patients.

Protective effect of nano vitamin D against fatty degeneration in submandibular and sublingual salivary glands: A histological and ultrastructural study

BackgroundPoor nutritional habits and a low level of physical activity are associated with obesity, leading to increased caloric and fat intakes. A high-fat diet can significantly impact oral health through the accumulation of lipids in the salivary glands, which ultimately affect salivary gland function. Recently, an increasing number of supplement nano-formulations, such as nano vitamin D, have become available. However, only few studies have explored the effects of nano vitamin D on the maintenance of oral health. ObjectiveThis study aimed to compare the histological effects of nano vitamin D to those of regular vitamin D on fatty degeneration in submandibular and sublingual salivary glands using a rat model. MethodsTwenty-four adult male albino Sprague–Dawley rats were divided into the following groups: untreated group, high-fat diet group, high-fat diet and regular vitamin D group, and high-fat diet and nano vitamin group.Thereafter, samples of the submandibular and sublingual salivary glands were dissected for histological and electron microscopic studies. Morphometric digital image analysis was used to quantitatively measure the changes in the size and number of acini and secretory granules. ResultsRegular vitamin D had a partial protective effect. However, vitamin D could fully restore cellular structures to their normal state, thereby protecting against fatty degeneration of the salivary tissue and immune cell infiltration, particularly in the submandibular serous tissue. Nano vitamin D was more efficacious than regular vitamin D at restoring the number and size of submandibular serous secretory granules. ConclusionEmploying nano vitamin D as a supplement to high-fat diets could protect against high-fat diet-induced salivary gland damage in rats.

Pathology of salivary gland dysfunction and restoration of function.

In this review, the author shows that simultaneous multiple disorders caused by reactivation of Epstein-Barr virus can lead to salivary gland disorders as part of Sjogren's syndrome (SS). Therefore, clinicians must differentiate SS from other diseases when diagnosing and treating salivary gland disorders. In particular, the author explains how microbial infection in SS overcomes immunological tolerance, leading to pathological changes, and how cytokine overexpression and endocrine disrupters contribute to glandular tissue injury. Also, the author suggests that involvement of reactive oxygen species is a common pathogenesis of salivary gland disorders and SS, so regulation of oxidative stress is an effective treatment for both. The results of clinical studies on restoring salivary gland function and regenerating salivary glands with tissue stem cells may provide clues on elucidating the cause of SS.

SMADS-Mediate Molecular Mechanisms in Sjögren's Syndrome.

There is considerable interest in delineating the molecular mechanisms of action of transforming growth factor-β (TGF-β), considered as central player in a plethora of human conditions, including cancer, fibrosis and autoimmune disease. TGF-β elicits its biological effects through membrane bound serine/threonine kinase receptors which transmit their signals via downstream signalling molecules, SMADs, which regulate the transcription of target genes in collaboration with various co-activators and co-repressors. Until now, therapeutic strategy for primary Sjögren’s syndrome (pSS) has been focused on inflammation, but, recently, the involvement of TGF-β/SMADs signalling has been demonstrated in pSS salivary glands (SGs) as mediator of the epithelial-mesenchymal transition (EMT) activation. Although EMT seems to cause pSS SG fibrosis, TGF-β family members have ambiguous effects on the function of pSS SGs. Based on these premises, this review highlights recent advances in unravelling the molecular basis for the multi-faceted functions of TGF-β in pSS that are dictated by orchestrations of SMADs, and describe TGF-β/SMADs value as both disease markers and/or therapeutic target for pSS.

Effects of photobiomodulation in salivary glands of chronic kidney disease patients on hemodialysis.

This randomized placebo-controlled trial evaluates the impact of photobiomodulation (PBMT) on the salivary flow and biochemistry of patients with chronic kidney disease (CKD) on hemodialysis. Forty-four patients on hemodialysis self-responded two questionnaires for oral health and salivary gland function perception. The subjects were evaluated for function of salivary glands and randomly allocated to two groups: PBMT group (three irradiations at 808 nm, 100 mW, 142 J/cm2, and 4 J per site); and placebo group. Patients were submitted to non-stimulated and stimulated sialometry and after the treatment at baseline and 14 days. Salivary volume and biochemical of the saliva were analyzed. At baseline, most subjects had self-perception of poor oral health (52.6%) and salivary dysfunction (63.1%). Clinical exam revealed that 47.3% of subjects presented dry mucosa. PBMT promoted increase of the non-stimulated (p = 0.027) and stimulated saliva (p = 0.014) and decrease of urea levels in both non-stimulated (p = 0.0001) and stimulated saliva (p = 0.0001). No alteration was detected in total proteins and calcium analysis. Patients with kidney disease can present alteration in flow, concentrations, and composition of saliva, affecting oral health, but our findings suggest that PBMT is effective to improve hyposalivation and urea levels in saliva of patients with CKD.

Development of a functional salivary gland tissue chip with potential for high-content drug screening

Radiation therapy for head and neck cancers causes salivary gland dysfunction leading to permanent xerostomia. Limited progress in the discovery of new therapeutic strategies is attributed to the lack of in vitro models that mimic salivary gland function and allow high-throughput drug screening. We address this limitation by combining engineered extracellular matrices with microbubble (MB) array technology to develop functional tissue mimetics for mouse and human salivary glands. We demonstrate that mouse and human salivary tissues encapsulated within matrix metalloproteinase-degradable poly(ethylene glycol) hydrogels formed in MB arrays are viable, express key salivary gland markers, and exhibit polarized localization of functional proteins. The salivary gland mimetics (SGm) respond to calcium signaling agonists and secrete salivary proteins. SGm were then used to evaluate radiosensitivity and mitigation of radiation damage using a radioprotective compound. Altogether, SGm exhibit phenotypic and functional parameters of salivary glands, and provide an enabling technology for high-content/throughput drug testing.

Neurofibromin expression by normal salivary glands

IntroductionNeurofibromin, a protein encoded by the NF1 gene, is mutated in neurofibromatosis 1, one of the most common genetic diseases. Oral manifestations are common and a high prevalence of hyposalivation was recently described in individuals with neurofibromatosis 1. Although neurofibromin is ubiquitously expressed, its expression levels vary depending on the tissue type and developmental stage of the organism. The role of neurofibromin in the development, morphology, and physiology of salivary glands is unknown and a detailed expression of neurofibromin in human normal salivary glands has never been investigated.AimTo investigate the expression levels and distribution of neurofibromin in acinar and ductal cells of major and minor salivary glands of adult individuals without NF1.Material and methodTen samples of morphologically normal major and minor salivary glands (three samples of each gland: parotid, submandibular and minor salivary; and one sample of sublingual gland) from individuals without neurofibromatosis 1 were selected to assess neurofibromin expression through immunohistochemistry. Immunoquantification was performed by a digital method.ResultsNeurofibromin was expressed in the cytoplasm of both serous and mucous acinar cells, as well as in ducts from all the samples of salivary glands. Staining intensity varied from mild to strong depending on the type of salivary gland and region (acini or ducts). Ducts had higher neurofibromin expression than acinar cells (p = 0.003). There was no statistical association between the expression of neurofibromin and the type of the salivary gland, considering acini (p = 0.09) or ducts (p = 0.50) of the four salivary glands (parotid, submandibular, minor salivary, and sublingual gland). Similar results were obtained comparing the acini (p = 0.35) and ducts (p = 0.50) of minor and major salivary glands. Besides, there was no correlation between the expression of neurofibromin and age (p = 0.08), and sex (p = 0.79) of the individuals, considering simultaneously the neurofibromin levels of acini and duct (n = 34).ConclusionNeurofibromin is expressed in the cytoplasm of serous and mucous acinar cells, and ductal cells of salivary glands, suggesting that this protein is important for salivary gland function.

Early Covert Appearance of Marginal Zone B Cells in Salivary Glands of Sjögren's Syndrome-Susceptible Mice: Initiators of Subsequent Overt Clinical Disease.

The C57BL/6.NOD-Aec1Aec2 mouse model has been extensively studied to define the underlying cellular and molecular bioprocesses critical in the onset of primary Sjögren’s Syndrome (pSS), a human systemic autoimmune disease characterized clinically as the loss of lacrimal and salivary gland functions leading to dry eye and dry mouth pathologies. This mouse model, together with several gene knockout mouse models of SS, has indicated that B lymphocytes, especially marginal zone B (MZB) cells, are necessary for development and onset of clinical manifestations despite the fact that destruction of the lacrimal and salivary gland cells involves a classical T cell-mediated autoimmune response. Because migrations and functions of MZB cells are difficult to study in vivo, we have carried out ex vivo investigations that use temporal global RNA transcriptomic analyses to profile autoimmunity as it develops within the salivary glands of C57BL/6.NOD-Aec1Aec2 mice. Temporal profiles indicate the appearance of Notch2-positive cells within the salivary glands of these SS-susceptible mice concomitant with the early-phase appearance of lymphocytic foci (LF). Data presented here identify cellular bioprocesses occurring during early immune cell migrations into the salivary glands and suggest MZB cells are recruited to the exocrine glands by the upregulated Cxcl13 chemokine where they recognize complement (C’)-decorated antigens via their sphingosine-1-phosphate (S1P) and B cell (BC) receptors. Based on known MZB cell behavior and mobility, we propose that MZB cells activated in the salivary glands migrate to splenic follicular zones to present antigens to follicular macrophages and dendritic cells that, in turn, promote a subsequent systemic cell-mediated and autoantibody-mediated autoimmune T cell response that targets exocrine gland cells and functions. Overall, this study uses the power of transcriptomic analyses to provide greater insight into several molecular events defining cellular bioprocesses underlying SS that can be modelled and more thoroughly studied at the cellular level.

Integration of metabolomics and transcriptomics reveals convergent pathways driving radiation-induced salivary gland dysfunction.

Radiation therapy for head and neck cancer causes damage to the surrounding salivary glands, resulting in salivary gland hypofunction and xerostomia. Current treatments do not provide lasting restoration of salivary gland function following radiation; therefore, a new mechanistic understanding of the radiation-induced damage response is necessary for identifying therapeutic targets. The purpose of the present study was to investigate the metabolic phenotype of radiation-induced damage in parotid salivary glands by integrating transcriptomic and metabolomic data. Integrated data were then analyzed to identify significant gene-metabolite interactions. Mice received a single 5 Gy dose of targeted head and neck radiation. Parotid tissue samples were collected 5 days following treatment for RNA sequencing and metabolomics analysis. Altered metabolites and transcripts significantly converged on a specific region in the metabolic reaction network. Both integrative pathway enrichment using rank-based statistics and network analysis highlighted significantly coordinated changes in glutathione metabolism, energy metabolism (TCA cycle and thermogenesis), peroxisomal lipid metabolism, and bile acid production with radiation. Integrated changes observed in energy metabolism suggest that radiation induces a mitochondrial dysfunction phenotype. These findings validated previous pathways involved in the radiation-damage response, such as altered energy metabolism, and identified robust signatures in salivary glands, such as reduced glutathione metabolism, that may be driving salivary gland dysfunction.

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.

Neurochemical regulation of Aedes aegypti salivary gland function

The salivary gland of hematophagous arthropods is critical for blood meal acquisition, blood vessel localization, and secretion of digestive enzymes. Thus, there is significant interest in the regulation of salivary gland function and mechanisms driving the secretion of saliva and digestive proteins. We aimed to gain a broader understanding of the regulatory role of aminergic, cholinergic, and octopaminergic neuromodulators to saliva and protein secretion from the female A. aegypti salivary gland. Quantification of saliva after injection with neuromodulators showed that dopamine, serotonin, and pilocarpine increased the secretory activity of the salivary gland with potency rankings dopamine = serotonin > pilocarpine. No change in saliva secretion was observed with octopamine or ergonovine, which indicates the A. aegypti salivary gland may be regulated by dopaminergic, serotonergic, and cholinergic systems, but are not likely regulated by octopaminergic or tryptaminergic systems. Next, we studied the regulatory control of dopamine-mediated salivation. Data indicate extracellular calcium flux, but not neural function, is critical for dopamine-mediated salivation, which suggests epithelial transport of ions and not neuronal control is responsible for dopamine-mediated salivation. For regulation of protein secretion, data indicate dopamine or serotonin exposure facilitates amylase secretion, whereas serotonin but not dopamine exposure increased apyrase concentrations in the secreted saliva. General immunoreactivity to anti-rat D1-dopamine receptor antibody was observed, yet immunoreactivity to the anti-rat D2-receptor antibody was identified in the proximal regions of the lateral lobes and slight immunoreactivity in the distal portion of the lateral lobe, with no expression in the medial lobe.

Strengthening the prevention and treatment of caries in patients receiving systemic therapy

The development of dental caries is affected by various factors. Patient's general health status can affect the risk of caries. Some systemic diseases may improve caries incidence or cause dental caries by changing oral microenvironment, affecting salivary gland function and salivary composition, and destroying dental structure directly or indirectly. The clinical symptoms and signs of caries associated with systemic diseases are different from common caries and this type of caries has its special strategy of prevention and therapy. The present review article analyzes the causes and mechanisms of caries susceptibility in patients receiving systemic therapy and systematically introduce the modern concepts of caries prevention and management in systemic therapy.

Salivary glands involvement: a new indicator of juvenile idiopathic oligoarticular arthritis (preliminary results).

Early diagnosis is critical to reduce long-term disability in patients with JIA by ensuring prompt treatment. The aim of this cross-sectional study was to evaluate the salivary gland function in JIA, addressing specifically oligoarticular (JIA1) and polyarticular (JIA2) subtypes, compared with healthy controls. This may contribute to the identification of salivary risk indicators of the disease that may help diagnosis at an early stage or even before the onset of other clinical evidence. Twenty-eight patients with JIA1, 28 patients with JIA2, according to the ILAR criteria, and 28 healthy controls (C) were included in the study. Exclusion criteria were any concurrent medical condition. Data on medication, dietary and oral hygiene habits were collected using a questionnaire. All patients underwent oral examination and saliva measurement. While stimulated salivary flow rate (SFR) was significantly lower in JIA1 compared with JIA2 and C (P < 0.001), both salivary buffer capacity and pH were similar in the two JIA groups but statistically different from C (P = 0.002 and P = 0.010, respectively). Children with very low SFR (<3.5 ml) exhibited a 16-fold higher likelihood of being affected by JIA1 rather than JIA2 (P = 0.003), while no association was observed between low flow rate and JIA subtype (P = 0.744). These preliminary data suggest impairment of salivary gland function as a risk indicator for JIA1 with no association with dietary habits and drug intake.

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

Hyperglycemia Induced Apoptosis Changes in Salivary Gland Cells of Mice

If the function of salivary glands that secrete saliva is degraded, saliva secretion will decrease and symptoms of xerostomia will appear. Although symptoms of xerostomia are often felt by patients with diabetes, the relationship between diabetes and xerostomia is currently unclear. In relation to DM, there are studies on salivation flow and saliva composition, but there are not studies of apoptosis of salivary gland cells. The objective of this study was to investigate whether apoptosis in salivary glands of mice with hyperglycemic, a symptom of diabetes, might be altered based on immunohistochemical analysis. This study used mice with hyperglycemia. Immunohistochemistry and Western blot analyses were performed using Fas, Bax, and cleaved caspase-3 antibodies. These antibodies are used not only as death receptors, but also are antibodies that activate upstream and downstream signals of apoptosis. TUNEL assay was performed to detect apoptosis by immunofluorescence using TdT enzyme. It was observed that the expression level of apoptosis signaling molecules and TUNEL positive cells were increased in hyperglycemia group (HG). As a result, there are many apoptosis cells in the HG groups of the salivary gland. The results of this study, the function of salivary gland could occur deteriorated due to apoptosis on salivary gland cells by hyperglycemic, a characteristic of diabetes.

Xerostomia diagnosis and management

Xerostomia, or dry mouth, is a common complaint that may be caused by several conditions, which include side effects of a wide variety of drugs, such as antidepressants, therapeutic radiation to the head and neck, dehydration, diabetes, and diseases involving salivary glands, such as Sjogren's syndrome. The complaint of dry mouth may or may not be associated with decreased salivary gland function. Individuals with xerostomia complain of problems with eating, speaking, swallowing, and wearing dentures. Some people also complain of salivary gland enlargement or changes in taste. Lack of saliva may predispose one to oral infections, such as candidiasis, and increase the risk of dental caries. Management of the individual patient with xerostomia includes assessment of salivary gland function, replacement therapy, and prevention of caries and oral candidiasis. Early recognition and management of xerostomia may prevent devastating dental disease and help to improve the quality of life.

Состояние твердых тканей зуба у лиц, переболевших COVID-19

Relevance. It is believed that the main cause of carious demineralization is microorganisms. However, the deterioration of the process is facilitated by the disruption of mineral metabolism in the oral cavity and, primarily, due to the insufficient supply of minerals naturally, from saliva. Aim: to study the effect of reduced functional activity of salivary glands on the intensity of the carious process and the sensitivity of teeth to stimuli in persons who have undergone COVID-19. Materials and methods. The studies involved 27 patients aged 18–42 years, 17 of them suffered from COVID-19. To compare the results, a group of individuals in the same age range who did not have COVID-19 was selected. All studied salivation rate, caries intensity, Green-Vermillon oral hygiene index (G-V), enamel solubility by TER test scale and the sensitivity of teeth to stimul. Results. In patients with COVID-19, immediately after recovery, pronounced hyposalivation (0.27±0.04 ml/min) was observed. After 1 year, this figure has not changed significantly; the intensity of caries increased by 35 %; the G-V index was at the middle level; the TER test had high rates and most of the patients with COVID-19 developed tooth hyperesthesia, which indicated that demineralization prevailed over remineralization. Conclusions. 1. In patients who have undergone COVID-19, enamel resistance decreases and the risk of developing a carious process increases and the appearance of hypersensitivity of teeth due to insufficient natural mineralization due to a decrease in the amount of saliva released – the main source of minerals entering the tooth enamel. 2. The microbial cantamination factor of demineralized enamel exacerbating the process is also not excluded. However, with good oral hygiene, the role of this factor is significantly reduced. 3. Persons who have undergone COVID-19 need dispensary supervision by a dentist, as well as medical and preventive measures that reduce the risk of developing a carious process. Key words: Patients who were sick with COVID-19; salivary gland function; enamel demineralization; caries intensity; tooth hypersensitivity.