Submandibular Gland Pathogenesis Following SARS-CoV-2 Infection and Implications for Xerostomia.

Although SARS-CoV-2 induces mucin hypersecretion in the respiratory tract, hyposalivation/xerostomia has been reported by COVID-19 patients. We evaluate the submandibular gland (SMGs) pathogenesis in SARS-CoV-2-infected K18-hACE2 mice, focusing on the impact of infection on the mucin production and structural integrity of acini, ductal system, myoepithelial cells (MECs) and telocytes. The spike protein, the nucleocapsid protein, hACE2, actin, EGF, TNF-α and IL-1ß were detected by immunofluorescence, and the Egfr and Muc5b expression was evaluated. In the infected animals, significant acinar hypertrophy was observed in contrast to ductal atrophy. Nucleocapsid proteins and/or viral particles were detected in the SMG cells, mainly in the nuclear membrane-derived vesicles, confirming the nuclear role in the viral formation. The acinar cells showed intense TNF-α and IL-1ß immunoexpression, and the EGF-EGFR signaling increased, together with Muc5b upregulation. This finding explains mucin hypersecretion and acinar hypertrophy, which compress the ducts. Dying MECs and actin reduction were also observed, indicating failure of contraction and acinar support, favoring acinar hypertrophy. Viral assembly was found in the dying telocytes, pointing to these intercommunicating cells as viral transmitters in SMGs. Therefore, EGF-EGFR-induced mucin hypersecretion was triggered by SARS-CoV-2 in acinar cells, likely mediated by cytokines. The damage to telocytes and MECs may have favored the acinar hypertrophy, leading to ductal obstruction, explaining xerostomia in COVID-19 patients. Thus, acinar cells, telocytes and MECs may be viral targets, which favor replication and cell-to-cell viral transmission in the SMG, corroborating the high viral load in saliva of infected individuals.

Salivary protein candidates for biomarkers of oral disorders in people with a crack cocaine use disorder.

The use of cocaine and its main derivative, crack, can cause some systemic effects that may lead to the development of some oral disorders. To assess the oral health of people with a crack cocaine use disorder and identify salivary protein candidates for biomarkers of oral disorders. A total of 40 volunteers hospitalized for rehabilitation for crack cocaine addiction were enrolled; nine were randomly selected for proteomic analysis. Intraoral examination, report of DMFT, gingival and plaque index, xerostomia, and non-stimulated saliva collection were performed. A list of proteins identified was generated from the UniProt database and manually revised. The mean age (n=40) was 32 (±8.88; 18-51) years; the mean DMFT index was 16±7.70; the mean plaque and gingival index were 2.07±0.65 and 2.12±0.64, respectively; and 20 (50%) volunteers reported xerostomia. We identified 305 salivary proteins (n=9), of which 23 were classified as candidate for biomarkers associated with 14 oral disorders. The highest number of candidates for biomarkers was associated with carcinoma of head and neck (n=7) and nasopharyngeal carcinoma (n=7), followed by periodontitis (n=6). People with a crack cocaine use disorder had an increased risk of dental caries and gingival inflammation; less than half had oral mucosal alterations, and half experienced xerostomia. As possible biomarkers for 14 oral disorders, 23 salivary proteins were identified. Oral cancer and periodontal disease were the most often associated disorders with biomarkers.

Salivary antioxidant enzymes associated with oral toxicity in haematopoietic cell transplantation: An observational study.

BACKGROUND: In haematopoietic cell transplantation (HCT), oral mucositis and xerostomia are related to conditioning-related oxidative stress. The role of salivary antioxidant enzymes in oral toxicity is poorly described. The aim of this study was to verify the association between salivary antioxidant enzymes and oral mucositis and xerostomia in HCT. DESIGN: Saliva from autologous and allogeneic HCT patients (n = 77) was selected before conditioning (T0), during the neutropenia period (T1) and after marrow engraftment (T2). Salivary flow, total salivary proteins, and superoxide dismutase, catalase and glutathione reductase activities were measured. RESULTS: There were no significant differences in salivary flow, total salivary proteins and catalase at the three HCT time points. Glutathione reductase levels were reduced at T1 compared to T0 (P = .013) and T2 (P = .001). Superoxide dismutase levels were increased from T0 to T2 (P = .013). Neither of these enzymes was associated with oral mucositis. Increased superoxide dismutase levels were associated with xerostomia frequency. Levels of this enzyme also showed significant correlation with days of xerostomia in T2 (ρ = .40, P = .002). CONCLUSIONS: Salivary antioxidant enzymes changed before and during early periods after HCT. The increase in salivary superoxide dismutase suggested partial activation of the salivary antioxidant system and was associated with xerostomia.

Unstimulated whole salivary flow in Sjögren's Syndrome: systematic literature review and meta-analysis

Abstract Background: Sjögren's Syndrome compromises the exocrine function, producing xerostomia and xerophthalmia. It can appear as an isolated condition or associated with other autoimmune diseases (polyautoimmunity). The Unstimulated Salivary Flow rate (UWSF) is used to quantify saliva production. There is no objective evidence to differentiate the values in patients with Sjögren's versus healthy people or patients with non-Sjögren's sicca. The objective of the present review was to evaluate the UWSF in patients with Sjögren's syndrome in comparison to controls (healthy and non-Sjögren's sicca patients). Methods: A systematic literature review was carried out (PRISMA guidelines). Analytical observational studies of cases and controls, cross-sectional studies, cohort studies and randomized clinical trials (including healthy controls) were considered. The Medline/OVID, Lilacs, Embase, and Cochrane/OVID databases were consulted. MeSH, DeCS, keywords, and Boolean operators were used. The meta-analysis (RevMan 5.2) was done through the random-effects model [mean difference (MD)]. Level and quality of evidence were evaluated by the Oxford Center Levels of Evidence and Joanna Brigs list respectively. Results: Thirty-two articles were included (20 were case-control studies,6 were cross-sectional,2 prospective cohort,2 retrospective cohort, and2 studies were abstracts) and 28 were meta-analyzed. The unstimulated whole salivary flow rate in the Sjögren's group was lower than in controls (healthy and patients with non-Sjögren Sicca syndrome) (MD-0.18 ml/min; 95% CI, −0.24 to −0.13; chi2-P-value <0.00001). Heterogeneity was 97% and there was publication bias (funnel plot). The level of evidence was mostly3 or 4. The quality of evidence was met (97% of items valued). Conclusion: For the first time, the unstimulated whole salivary flow rate is found to be lower in patients with Sjögren's syndrome compared to controls (healthy and non-SS sicca) through a meta-analysis. (AU)

Evaluation of photobiomodulation in salivary production of patients with xerostomy induced by anti-hypertensive drugs: Study protocol clinical trial (SPIRIT compliant).

INTRODUCTION: Hypertension (systemic arterial hypertension [SAH]) is a systemic condition that affects about 30% of the world population, according to data from the World Health Organization (WHO). Drugs used to control this disease have the potential to induce xerostomia, an oral condition in which the decrease of the salivary flow is observed and whose presence leads to the increase of the index of caries, periodontal disease, loss of the teeth, dysgeusia, difficulty of mastication, dysphagia, bad breath and oral burning and impairment of prothesis installed in the buccal cavity, including retention of removable and total dentures. METHODS: This is a randomized, placebo-controlled, blind clinical protocol that aims to analyze the impact of phobiomodulation (PBM) on salivary glands of patients with antihypertensive drug induced xerostomia. Patients will be divided into 2 groups: G1: older adults with xerostomia induced by antihypertensive drugs and treatment with PBM (n = 30); G2: placebo PBM (n = 30). The irradiation will be made using a diode laser emitting at 808 nm with 100 mW and 40 seconds of exposure per site at the salivary glands. Twenty sites will be irradiated weekly for 4 weeks. Non-stimulated and stimulated salivary flow will be analyzed before and after the treatment. RESULTS: This protocol will determine the effectiveness of photodynamic therapy regarding the reduction of xerostomia in older adults using antihypertensive drugs. CONCLUSION: This protocol will determine the effectiveness of photodynamic therapy regarding the reduction of xerostomia in older adults using antihypertensive drugs. TRIAL REGISTRATION: Clinicaltrials.gov - NCT03632096.

Aberrant MUC1 accumulation in salivary glands of Sjögren's syndrome patients is reversed by TUDCA in vitro.

OBJECTIVES: Xerostomia in SS patients has been associated with low quality and quantity of salivary mucins, which are fundamental for the hydration and protection of the oral mucosa. The aim of this study was to evaluate if cytokines induce aberrant mucin expression and whether tauroursodeoxycholic acid (TUDCA) is able to counteract such an anomaly. METHODS: Labial salivary glands from 16 SS patients and 15 control subjects, as well as 3D acini or human submandibular gland cells stimulated with TNF-α or IFN-γ and co-incubated with TUDCA, were analysed. mRNA and protein levels of Mucin 1 (MUC1) and MUC7 were determined by RT-qPCR and western blot, respectively. Co-immunoprecipitation and immunofluorescence assays for mucins and GRP78 [an endoplasmic reticulum (ER)-resident protein] were also performed. mRNA levels of RelA/p65 (nuclear factor-κB subunit), TNF-α, IL-1ß, IL-6, SEL1L and EDEM1 were determined by RT-qPCR, and RelA/p65 localization was evaluated by immunofluorescence. RESULTS: MUC1 is overexpressed and accumulated in the ER of labial salivary gland from SS patients, while MUC7 accumulates throughout the cytoplasm of acinar cells; however, MUC1, but not MUC7, co-precipitated with GRP78. TUDCA diminished the overexpression and aberrant accumulation of MUC1 induced by TNF-α and IFN-γ, as well as the nuclear translocation of RelA/p65, together with the expression of inflammatory and ER stress markers in 3D acini. CONCLUSION: Chronic inflammation alters the secretory process of MUC1, inducing ER stress and affecting the quality of saliva in SS patients. TUDCA showed anti-inflammatory properties decreasing aberrant MUC1 accumulation. Further studies are necessary to evaluate the potential therapeutic effect of TUDCA in restoring glandular homeostasis in SS patients.

Aspectos relevantes da síndrome de Sjõgren para o cirurgião-dentista / Sjogren’s syndrome’s relevant aspects for the dental surgeon

A síndrome de Sjõgren (SS), conhecida como síndrome sicca, é uma doença autoimune caracterizada pela hipofunção das glândulas salivares e lacrimais, cuja prevalência na população mundial é de aproximadamente 0,5% a 1%. Por ser uma doença autoimune complexa e de difícil diagnóstico, é sub-diagnosticada e sub-tratada segundo o consenso realizado em 2012 pelo Colégio Americano de Reumatologia (ACR). O Cirurgião-Dentista pode desempenhar papel importante na detecção de possíveis alterações compatíveis com a síndrome, além de auxiliar no tratamento de diversas patologias orais decorrentes da síndrome. Este trabalho tem como objetivo explanar aspectos importantes referentes ao diagnóstico e tratamento da síndrome aqui discutida. A SS apesar de ser considerada uma doença de evolução lenta, em estágios avançados pode ser fatal, principalmente por aumentar as chances dos pacientes virem a desenvolver linfoma não Hodking. O tratamento odontológico dos pacientes com SS deve principalmente ser profilático, com a recomendação do uso de repositores de saliva e controle rígido da higiene bucal.

Sjogren’s syndrome (SS), known as the sicca syndrome, is an autoimmune disease characterized by salivary and lacrimal glands hypofunction which prevalence in the world population is approximatel y around 0,5% to 1%. For being a complex autoimmune disease and with difficult diagnosis, it is sub diagnosed and miss treated according to the consensus occurred in 2012 by the American College of Rheumatology (ACR). The surgeon-dentist (SD) may play a important role on the detection of possible changes compatible to the syndrome, besides can help in the treatment of many oral pathologies caused by the syndrome. This work has the main purpose to explain the important aspects regards to the correct diagnosis and treatment of this syndrome.The SS besides been considered a slow evolution disease, in advanced stages it can be fatal,mainly for increasing the patient’s chances of developing non-Hodking lymphoma. The dental treatment of patients with SS must be prophylactic, with the recomedations of the use of salivary replenishing and careful control of the oral hyigiene.

Hemodialysis-specific factors associated with salivary flow rates.

The saliva is important to maintain the integrity of tissues and teeth, besides having microbial activity. Hemodialysis (HD) patients usually have reduced salivary flow rate (SFR) and are exposed to all its associated complications. The aim of the present study was to identify HD-related factors associated with reduced SFR. A cross-sectional study was performed with maintenance HD patients. Stimulated whole saliva was collected before and after HD. Xerostomia was assessed through the validated xerostomia inventory and thirst through the dialysis thirst inventory. Parameters of dental health status were obtained by the decayed, missed, and filled teeth index and community periodontal index. One hundred twenty-eight patients (66 males) participated in this study. Stimulated SFR before HD was 0.38 ± 0.28 mL/min. In univariate analysis and after adjusting for several factors, serum urea before HD session, serum intact parathormone (iPTH), calcium-phosphorus product (Ca×Pi), serum ferritin, and number of medications were negatively correlated with SFR in univariate analysis. Moreover, patients taking sevelamer had reduced SFR in comparison with those not receiving it (SFR 0.32 ± 0.19 vs. 0.44 ± 0.23 mL/min, P = 0.003). At multivariate analysis, including dialysis and nondialysis-related factors, age, elevated pre-HD serum urea, higher Ca×Pi product, higher iPTH, and sevelamer use remained as factors that were independently associated with a reduced SFR. After dialysis, there was a significant increment in SFR (0.39 ± 0.28 vs. 0.60 ± 0.34 mL/min, P < 0.001). Several HD-related features were associated with reduced SFR, including serum urea, sevelamer use, and bone and mineral disorders markers.

Sialometry of upper labial minor glands: a clinical approach by the use of weighing method Schirmer's test strips paper.

OBJECTIVES: To establish referential values ranges of hyposalivation and normosalivation for the salivary flow rate (SFR) of upper labial (LS) and palatal (PS) mucosa using Schirmer's test strips paper and as a second goal to determine the values ranges of the SFR of palatal (PS) and upper labial (LS) mucosa in subjects with and without xerostomia. METHODS: A cross-sectional study was conducted among subjects distributed in three groups according to their unstimulated and stimulated whole saliva. RESULTS: 144 subjects were enrolled in groups as follows: severe hyposalivation (n = 24), mild hyposalivation (n = 78), and normosalivation (n = 42). The mean and the 95% confidence interval for the LS flow rate ( µ L/cm(2)/min) were 3.2 (2.46 to 3.94), 5.86 (4.96 to 6.75), and 9.08 (7.63 to 10.53) (P < 0.001) for each group, respectively. The PS results were 1.01 (0.68 to 1.34), 1.72 (1.31 to 2.13), and 2.44 (1.66 to 3.22) (P = 0.014). Xerostomia complainers presented lower rates of LS (5.17 (4.06 to 6.23)) than non-complainers (7.33 (6.4 to 8.27)) (P = 0.003). CONCLUSIONS: The test was reliable to provide referential values ranges for LS flow rate measurement and was shown to be valid to distinguish normosalivation from severe and mild hyposalivation and also to predict xerostomia.

Endocannabinoids mediate hyposalivation induced by inflammogens in the submandibular glands and hypothalamus.

OBJECTIVE: The aim of this study was to investigate the factors that could participate on salivary glands hypofunction during inflammation and the participation of endocannabinoids in hyposalivation induced by the presence of inflammogens in the submandibular gland (SMG) or in the brain. DESIGN: Salivary secretion was assessed in the presence of inflammogens and/or the cannabinoid receptor antagonist AM251 in the SMG or in the brain of rats. At the end of the experiments, some systemic and glandular inflammatory markers were measured and histopathological analysis was performed. RESULTS: The inhibitory effect observed 1h after lipopolysaccharide (LPS, 50µg/50µl) injection into the SMG (ig) was completely prevented by the injection of AM251 (5µg/50µl) by the same route (P<0.05). The LPS (ig)-induced increase in PGE2 content was not altered by AM251 (ig), while the glandular production of TNFα induced by the endotoxin (P<0.001) was partially blocked by it. Also, LPS injection produced no significant changes in the wet weight of the SMG neither damage to lipid membranes of its cells, nor significant microscopic changes in them, after hispopathological analysis, compared to controls. Finally, TNFα (100ng/5µl) injected intracerebro-ventricularly (icv) inhibited methacholine-induced salivary secretion evaluated 30min after (P<0.01), but the previous injection of AM251 (500ng/5µl, icv) prevented completely that effect. CONCLUSION: We conclude that endocannabinoids mediate the hyposialia induced by inflammogens in the SMG and in the brain. The hypofunction would be due to changes on signalling pathway produced by inflammatory compounds since anatomical changes were not observed.

Oral dryness in Sjögren's syndrome patients. Not just a question of water.

Sjögren's syndrome (SS) is a chronic autoimmune disease of undefined etiology. Patients with this syndrome suffer from severe alterations in both the quality and quantity of saliva and tears, due to impaired function of the relevant exocrine glands. Prevalent symptoms experienced by SS-patients include a persistent dry mouth sensation (xerostomia) and dry eyes (keratoconjunctivitis sicca). Water content of saliva depends of acetylcholine levels, glandular innervation, M3R signaling, calcium tunneling and water release, among other factors. However, unstimulated salivary flow correlates only poorly with symptoms of mouth dryness, raising the question as to which other components of saliva may be involved in mouth dryness experienced by SS-patients? Salivary mucins are glycoproteins characterized by the presence of large oligosaccharide side chains attached to the protein backbone. These molecules are key saliva components that are required to sequester water and thereby moisturize, as well as lubricate the oral mucosa. In the labial salivary glands of SS patients, morphological and functional alterations are detectable that affect the maturation and trafficking of salivary mucins. In this review, we will focus the discussion on these aspects of reduced salivary flow and decreased quality of salivary mucins, since they are likely to be responsible for xerostomia in SS-patients.

Spontaneously hypertensive rat as experimental model of salivary hypofunction.

OBJECTIVE: To analyse the salivary activity in spontaneously hypertensive rats (SHRs) evaluating biochemical parameters of saliva in 4-week-old and 12-week-old animals. DESIGN: Systolic blood pressure (SBP) was recorded by tail plethysmography. The salivary flow rate was stimulated by pilocarpine (SFR). The pH and salivary buffering capacity (SBC) were evaluated with a specific electrode. The concentrations of fluoride ([F(-)]) and calcium ([Ca(++)]) ions were determined using an electrode connected to a calibrated ion analyser. The total protein concentration was determined by Lowry method, and amylase activity by kinetic method. The salivary IgA was determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: The SFR, [F(-)] and [Ca(++)] increased with age in normotensive rats, however no alteration in pH, total protein and IgA was observed between 4 and 12 weeks old Wistar rats. SBC decreased with age in Wistar rats. The SFR was not altered between SHRs in different ages and it was lower in 12 weeks old SHR when compared to Wistar rats. An increase in the protein concentration, and in the amylase activity and [F(-)] was observed with the development of SHR. Unaltered SBC, salivary IgA and [Ca(++)] were observed in 12 weeks old when compared to 4 weeks old SHR. The [Ca(++)] ions were reduced in saliva of SHR than that of Wistar rats at 12 weeks. A lower pH was observed in saliva of Wistar than that of SHR at 12 weeks. CONCLUSIONS: SHR is an experimental model of salivary hypofunction, the decreased SFR observed in SHR at different ages was associated to salivary biochemical parameter alterations.

Xerostomia in Sjögren's syndrome and lupus erythematosus: a comparative histological and immunofluorescence study of minor salivary glands alterations.

BACKGROUND: Xerostomia is a symptom that can be triggered by chronic diseases such as Sjögren's syndrome (SS) and lupus erythematosus (LE). Many authors regard most cases of salivary hypofunction in LE to secondary SS. Others believe that salivary changes in patients with LE might reflect a multisystem presentation of the disease. The present study compared histopathological and direct immunofluorescence (DIF) alterations in salivary glands of patients with xerostomia and diagnosis of LE or SS. METHODS: Twenty-eight salivary gland biopsies from patients with xerostomia and diagnosed with LE or SS were submitted to histopathological and DIF exams. RESULTS: From the 28 patients, 16 had SS and 12 had LE. In SS, a moderate to intense sialadenitis was detected, with infiltration and destruction of excretory salivary ducts. In LE, mild/moderate sialadenitis with thickening and hyalinization of the ductal basement membrane was observed. DIF revealed that 50% of SS patients presented intercellular ductal IgA deposits, whereas 58% of LE patients showed deposits of IgG in the ductal basement membrane. CONCLUSIONS: Alterations in salivary glands of LE patients may be a specific manifestation of the disease (lupus sialadenitis), reflecting its multisystemic presentation, instead of an association of secondary SS and LE.

Reduced sulfation of muc5b is linked to xerostomia in patients with Sjögren syndrome.

OBJECTIVES: MUC5B contains sulfated and sialylated oligosaccharides that sequester water required for moisturising the oral mucosa. Xerostomia, in patients with Sjögren syndrome, is generally associated with reduced quantities, rather than altered properties, of saliva. Here, we determined the amount of MUC5B (mRNA and protein) as well as sulfation levels in salivary glands of patients with normal or altered unstimulated salivary flow. Localisation of MUC5B and sulfated MUC5B, as well as total levels sulfated groups were determined and compared with acini basal lamina disorganisation. PATIENTS AND METHODS: In all, 18 patients with normal or altered unstimulated salivary flow and 16 controls were studied. MUC5B mRNA and protein were evaluated in salivary glands by semiquantitative RT-PCR and Western blot analysis. MUC5B sulfation was determined by Western blotting. MUC5B and sulfo-Lewis(a) antigen localisation were assessed by immunohistochemistry. The total amount of sulfated oligosaccharides was determined microdensitometrically. RESULTS: No significant differences were detected in MUC5B mRNA and protein levels between controls and patients, while sulfo-Lewis(a) antigen levels were lower in patients. The number of sulfo-Lewis(a) positive mucous acini was reduced in patients but no correlation was observed between lower levels of sulfation and unstimulated salivary flow. Microdensitometric data confirmed the presence of reduced sulfated oligosaccharides levels in mucous acini from patients with highly disorganised basal lamina. CONCLUSION: Disorganisation of the basal lamina observed in patients with Sjögren syndrome may lead to dedifferentiation of acinar mucous cells and, as a consequence, alter sulfation of MUC5B. These changes are suggested to represent a novel mechanism that may explain xerostomia in these patients.

Decrease in salivary secretion by radiation mediated by nitric oxide and prostaglandins.

OBJECTIVE: In the present work, we evaluated the effect of exposing the submandibular glands (SMG) to radiation, studying different functional parameters such as salivary secretion, nitric oxide (NO) production, reactive oxygen species formation, prostaglandin (PGE) content and apoptosis. METHODS: We irradiated rats in the head and neck region with a single dose of gamma-ray radiation of 15 Gy. Two hours after radiation, we measured norepinephrine-induced salivary secretion. After that, the SMG were dissected, and in this tissue, we measured the activity of NO synthase (NOS), the PGE content, the amount of reactive oxygen species, apoptotic cells and mitochondrial inducible NOS (iNOS) expression. RESULTS: We found that radiation decreased salivary secretion when 10 and 30 microg/kg of norepinephrine was administered via the right femoral vein. We observed that iNOS activity was reduced and PGE content increased after radiation in SMG, indicating that NO and PGEs may participate in salivary secretion. The expression of mitochondrial NOS was increased after radiation leading to the formation of large amounts of NO that acts as a proapoptotic signal. In fact, we observed an augmentation in apoptotic cells. In this study, we also observed an increase in lipid peroxidation induced by radiation that may contribute to tissue damage. CONCLUSIONS: Our results indicate that radiation induced a decrease in salivary secretion and SMG iNOS activity, meanwhile the PGE content, the lipid peroxidation and apoptosis increased in the tissue. These modifications decrease salivary secretion.

Major salivary gland damage in allogeneic hematopoietic progenitor cell transplantation assessed by scintigraphic methods.

Salivary gland dysfunction is a common sequela of hematopoietic progenitor cell transplantation (HPCT). The investigation of major salivary gland dysfunction with sodium pertechnetate scintigraphy is a non-invasive method that provides images of the parotid and submandibular glands. In this prospective trial, 20 HPCT patients were submitted to scintigraphic study with 99mTc-pertechenate and 67Ga in order to evaluate the major salivary glands early involvement following HPCT. Major salivary glands were evaluated prior to HCPT as well as at Days +30, +60 and +100 post transplant. Major salivary glands uptake and clearance of 99mTc-pertechenate results did not demonstrate any functional differences between pre- versus post transplant periods. Results of the 67Ga scan revealed inflammatory infiltration following HPCT, primarily in submandibular glands, suggest a persistent involvement of major salivary glands up to Day +100 after HPCT.

[Non-neoplastic enlargement of salivary glands: clinico-histologic analysis]. / Agrandamiento no neoplásico de glándulas salivales. Análisis clínico-histológico.

We carried out a retrospective study on non-neoplastic enlargement of the salivary glands at the Oral Histopathology Diagnostic Center of the Autonomous Metropolitan University at Xochimilco (UAM-Xochimilco) in Mexico during a period of 24 years (1979-2003). From 5,625 biopsies received and analyzed, a total of 461 (8.2%) were non-neoplastic enlargement of the salivary glands; for each case, we registered demographic data as well as clinic characteristics. These lesions were characterized as a heterogeneous group of pathologic entities among which we included local, obstructive, infectious, and immunopathologic lesions. The most frequent lesion was the extravasation cyst in 341 (74%) cases, followed by chronic sialoadenitis and Sjögren's syndrome with 54 (11.7%) and 41 (8.8%) cases, respectively, and at a lesser percentage mucous retention cyst, sialosis, benign lymphoepithelial lesions and those related with sialolytes. Females were affected more frequently; mean age was second to third life decades. These lesions were most frequently localized on inferior labial mucosa.

Opposite effects of antidepressants on unstimulated and stimulated salivary flow.

In this study, effects on both stimulated and non-stimulated salivary flow as well as salivary components of different antidepressant drugs were compared. Rats received imipramine (IMI; 10mg/ml), fluoxetine (FLU; 20 mg/ml) or moclobemide (MOC; 30 mg/ml) by gavage. The drugs were administered 24, 5 and 1 h before saliva collection (sub-acute treatment) or as a once a day treatment for 14 days (chronic treatment). Animals were sedated with thiopental and saliva was collected using pre-weighed cotton balls inserted in the mouth for 1 min before and after pilocarpine stimulus. Pilocarpine-stimulated saliva was also collected for biochemical assays of total proteins, amylase, phosphate and calcium, performed through automated colorimetric methods. Non-stimulated salivary flow was decreased by sub-acute IMI 10 mg/kg treatment. Pilocarpine-stimulated salivary flow was significantly increased by acute treatments with IMI, FLU and MOC in comparison to the control group. The same opposite pattern of effects on non-stimulated and pilocarpine-stimulated salivation was seen after chronic treatment with the antidepressants. Increased levels of calcium following sub-acute treatment with IMI and after prolonged treatment with FLU and MOC were detected. In the assayed samples, phosphate was found to be increased following chronic treatment with FLU or MOC. These results may explain the discrepant effects of the antidepressants on salivation described in pre-clinical and clinical studies.

Clinical and biochemical evaluation of the saliva of patients with xerostomia induced by radiotherapy.

Clinical aspects and biochemical properties in the saliva of 21 patients prior to and following radiotherapy for head and neck cancer were evaluated (experimental group) and compared with the same properties in a control group of 21 subjects free of cancer. Salivary flow was evaluated by measuring the time necessary, in seconds, for the output of 2 ml of stimulated saliva; and the buffering capacity changes were determined using a simple colorimetric method. Total salivary protein concentration was determined by the Bradford 4 method. Amylase activity was measured by reducing sugars released from a soluble starch substrate, quantified by the dinitrosalicylic method. The electrophoretic profile was evaluated in polyacrylamide gel (12% SDS-PAGE) using samples of 5 mg of salivary protein. A statistically significant reduction (p < 0.01) of the salivary flow was observed, (162.47 s +/- 28.30 before and 568.71 s +/- 79.75 after irradiation), as well as a reduction in the salivary buffering capacity (pH 5.45 +/- 0.14 before and pH 4.40 +/- 0.15 after irradiation). No statistically significant alteration was observed in total salivary protein concentration. A statistically significant reduction (p < 0.01) of salivary alpha-amylase activity (856.6 ng/mg +/- 88.0 before and 567.0 ng/mg +/- 120.6 after irradiation) was observed. Electrophoretic profile differences in salivary protein bands were also observed after radiotherapy, mainly in the range of molecular weight of 72000 to 55000 Daltons. Clinically, patients presenting xerostomia induced by radiotherapy presented an increase in oral tissue injury.

Clinical and biochemical evaluation of the saliva of patients with xerostomia induced by radiotherapy

Foram avaliados alguns aspectos clínicos e algumas propriedades bioquímicas salivares de 21 pacientes, antes e após o tratamento radioterápico para câncer de cabeça e pescoço (grupo experimental) e de 21 pacientes sem câncer (grupo controle). O fluxo salivar foi avaliado pelo tempo necessário (segundos) para produção estimulada de 2 ml de saliva e a capacidade tamponante determinada frente à utilização de um método colorimétrico simples. A concentração de proteína total salivar foi determinada pelo método de Bradford4. A atividade da amilase foi mensurada através dos açúcares redutores liberados e quantificados pelo método do ácido dinitrossalicílico utilizando a glicose como substrato. O perfil eletroforético foi avaliado em gel de poliacrilamida (SDS-PAGE 12%) para amostras salivares contendo 5 mg de proteína. Foi observada, no grupo experimental, redução estatisticamente significativa (p < 0,01) para o fluxo salivar (162,47 s ± 28,30 antes e 568,71 s ± 79,75 após) e para a capacidade tamponante (pH 5,45 ± 0,14 antes e 4,40 ± 0,15 após). Não foi observada alteração estatisticamente significativa na concentração de proteína. A atividade específica da a-amilase foi significativamente diminuída (p < 0,01) (856,6 ng/mg ± 88,0 antes e 567,0 ng/mg ± 120,6 após). No perfil eletroforético, foram observadas diferenças nas bandas protéicas, principalmente na faixa de peso molecular de 72.000 a 55.000 Da. Clinicamente, os pacientes com xerostomia induzida pela radioterapia apresentaram aumento de lesões na mucosa.