Factors Associated with Hyposalivation in Brazilian Adults

ABSTRACT Objective: To determine the occurrence of hyposalivation in Brazilian adults and its association with individual determinants, such as the use of medications, systemic conditions, smoking, and alcohol consumption. Material and Methods: A cross-sectional study with 402 adults was developed. Information was collected on sociodemographic and general health characteristics, and sialometry was performed with stimulated salivary flow. It indicated low salivary flow when ≤ 0.7 mL/min. Bivariate and multivariate analyses were conducted using a decision tree (p<0.05). Results: The sample was comprised predominantly of women (68.2%) aged ≤ 29 years (25.4%). Most participants did not use medication (56.7%). Among systemic diseases, the most cited was hypertension (25.1%). More than a third of the participants presented hyposalivation (40.3%), being associated with the following variables: age between 50 to 59 years (p=0.011), female sex (p<0.001), menopause (p=0.001), use of alcohol (p=0.033), systemic disease (p=0.002) and medication use (p<0.001). In multivariate analysis, in addition to sex (p<0.001) and hypertension (p=0.005), an association was also found between hyposalivation and diabetes (p=0.014). Conclusion: Factors associated with hyposalivation in adults were sex and the presence of hypertension or diabetes.

Prevalence of oral injuries and salivary changes in patients with chronic renal failure on hemodialysis: systematic review and meta-analysis

The objective of this study was to evaluate whether individuals with chronic renal failure (CRF) undergoing hemodialysis treatment have more salivary and oral mucosa alterations when compared to healthy individuals, through a systematic review followed by meta-analysis. A systematic literature review was performed, evaluating randomized clinical trials found in the Proquest, Embase, Scopus, Cochrane Library, Web of Science, Lilacs and Pubmed databases, using MeSH terms and other keywords. Initially, 40 articles were included in the study and, after reading the complete articles, only 15 clinical trials that analyzed oral lesions and salivary changes in patients with CRF undergoing hemodialysis treatment were eligible. Most of the clinical studies included were cross-sectional and composed of a study group and a control group. The mean age of participants in the study group was 50.19 years and in the control group, 48.95 years. The most common oral alterations found in the CRF group in relation to the control group were xerostomia, uremic breath, dysgeusia, coated tongue, gingival bleeding and pale mucosa. The salivary flow of patients with CRF was 46.6% lower than the control group. The salivary pH in the study group was also more alkaline when compared to the control group. Greater amounts of urea, phosphate, C-reactive protein and total proteins were found in the saliva of individuals with CRF. Individuals with CRF undergoing hemodialysis are more prone to changes in both the quantity and quality of saliva, as well as having a greater amount of oral changes.

Prevalence of xerostomia and its association with systemic diseases and medications in the elderly: a cross-sectional study

ABSTRACT BACKGROUND: Dry mouth syndrome or xerostomia is defined as decreased salivary flow or hypofunction of salivary glands. Its origins are multicausal and might be the result of a change in the salivary glands or a systemic imbalance. OBJECTIVE: To ascertain the prevalence of self-reported xerostomia and to identify associated factors. DESIGN AND SETTING: Cross-sectional study on the entire population of 293 elderly people over 60 years of age living in a Brazilian municipality. METHODS: Data were gathered from a questionnaire that asked about demographic data, chronic diseases and use of continuous medications, and which used the Xerostomia Inventory (XI) to evaluate dry mouth sensation. Our analysis consisted of multivariate regression and estimation of odds ratios (OR) and their respective 95% confidence intervals (CI) in binary logistic regression models. RESULTS: The prevalence of self-reported xerostomia was 19.1%. Elderly people with diabetes had higher odds of having self-reported xerostomia (OR: 3.59; 95% CI: 1.48-8.68; P < 0.001) as did those who had chronic diseases and used continuous medication (OR: 2.3; 95% CI: 1.19-4.67; P = 0.009). Elderly people who used continuous medication for the gastrointestinal tract were more likely to have xerostomia (OR: 2.14; 95% CI: 1.03-1.44; P = 0.030). CONCLUSIONS: Elderly people with diabetes and chronic diseases who were using continuous medication were more likely to have dry mouth. Use of continuous medications for the gastrointestinal tract led to a greater chance of having self-reported xerostomia.

Relationship Between Xerostomia and Hyposalivation in Senior Chilean People

ABSTRACT: Background: Hyposalivation is an objective decrease in salivary flow and it can produce xerostomia; which is a subjective sensation of dry mouth, common condition in senior population. Objectives: To identify the association between xerostomia and hyposalivation and its risk factors in people aged 60 years and older, and to investigate the association with medications, habits and other oral complications. Methods: 211 participants were included. Xerostomia data was collected using a validated Spanish-Xerostomia Inventory (XI-sp). Unstimulated whole-salivary flow rates were measured to detect hyposalivation. Results were analyzed using Chi-square, Fisher tests and multivariate logistic regression analysis. p <.05. Results: No significant association was detected between Xerostomia and Hyposalivation (p=.0666). Xerostomia 84.3%(p=.036) and hyposalivation 81.4%(p=.004) occur more frequently in women. A significant association was found between hyposalivation with the female gender (OR = 2.46, 95% confidence interval (CI): 1.19-5.11, p=0.015); denture stomatitis (OR=3.71, 95% CI:1.03-13.3, p=0.045) and atrophic glossitis (OR=3.72, 95% CI:1.78-8.1, p=0.001). Only female gender (OR=2.54; 95% CI:1.19-5.43, p=0.016) was significantly associated with xerostomia. Conclusions: No statistically significant association was found between hyposalivation and xerostomia. A significant association was found between oral candidiasis, denture stomatitis and the atrophic tongue with hyposalivation. Being woman was a risk factor for xerostomia and hyposalivation.

How common is dry mouth? systematic review and meta-regression analysis of prevalence estimates

Abstract The aim of this paper is to systematically review the literature to estimate the overall prevalence of xerostomia/hyposalivation in epidemiological studies. An electronic search was carried out up to February 2018 with no language restrictions. A total of 5760 titles were screened and just twenty-nine papers were included in review and the meta-analysis after a two independently reviewers applied the selection criteria. Data were extracted from PubMed and Web of Science databases. Eligibility criteria included original investigations from observational population-based studies that reported the prevalence of xerostomia or data that allowed the calculation of prevalence of xerostomia and/or hyposalivation. Studies conducted in samples with specific health conditions, literature reviews, case reports and anthropological studies, as conferences or comments were excluded. Sample size, geographic location of the study, study design, age of the studied population, diagnosis methods, and evaluation criteria used to determine xerostomia e/or hyposalivation were extracted for meta-analysis and meta-regression. Multivariate meta-regression analysis was performed to explore heterogeneity among studies. The overall estimated prevalence of dry mouth was 22.0% (95%CI 17.0-26.0%). Higher prevalence of xerostomia was observed in studies conducted only with elderly people. Despite diverse approaches to the condition's measurement, just over one in four people suffer from xerostomia, with higher rates observed among older people. Moreover, the measurement methods used currently may over- or underestimate xerostomia. These findings highlight the need for further work on existing and new clinical measure and will be useful to determine which one is more reliable in clinical and epidemiological perspectives.

Resumo O objetivo do estudo é revisar sistematicamente a literatura afim de estimar a prevalência global de xerostomia/hiposalivação em estudos epidemiológicos. Uma busca eletrônica foi conduzida até Fevereiro de 2018 sem restrições de linguagem. Um total de 5760 títulos foram inicialmente identificados e somente vinte e nove artigos foram incluídos na revisão e meta-análise após dois revisores independentes aplicarem os critérios de seleção. Os artigos foram extraídos das bases de dados PubMed/Medline e Web of Science. Os critérios de elegibilidade incluíram investigações originais de estudos observacionais de base populacional os quais reportaram a prevalência de xerostomia ou dados que permitissem o cálculo da prevalência de xerostomia e/ou hiposalivação. Estudos realizados em populações com condições de saúde específicas, revisões de literatura, relato de casos e estudos antropológicos, assim como, conferências ou comentários foram excluídos. Tamanho amostral, localização geográfica aonde foi realizado o estudo, desenho do estudo, idade da população estudada, métodos de diagnóstico e o critério de avaliação para determiner xerostomia e/ou hiposalivação foram extraídos para a meta-análise e metaregressão. Análise de meta-regressão multípla foi realizada para explorar a heterogeneidade entre os estudos. A prevalência global estimada de boca seca foi de 22.0% (95%IC 17.0-26.0%). Uma maior prevalência de xerostomia foi observada em estudos realizados exclusivamente em populações idosas. Apesar de diferentes abordagens utilizadas para mensurar as condições de interesse, cerca de uma em quatro pessoas é acometida por xerostomia, com taxas mais elevadas sendo observadas na população idosa. Além disso, os métodos de mensuração podem ter super- ou subestimado os valores de xerostomia. Os achados do presente estudo salientam a necessidade de mais estudos acerca das existentes e novas formas de avaliação clínica, os quais serão úteis para determinar qual é a mais confiável para as perspectivas clínicas e epidemiológicas.

Valoración de técnicas de citología en mucosa bucal en pacientes con síndrome de Sjögren / Assessment of cytology techniques in oral mucosa of Sjögren's syndrome patients

Resumen El objetivo del presente trabajo es comparar dos técnicas de estudio de citología bucal, la citología exfoliativa y de impresión, para evaluar cambios en la mucosa oral que permitan el diagnóstico no invasivo de síndrome de Sjögren (SS). Pacientes: Se seleccionaron 50 pacientes apareados por sexo y edad, diagnosticados con síndrome de Sjögren según criterios del Consenso Americano-Europeo. Los pacientes fueron distribuidos en tres grupos experimentales: controles sanos (C), n = 14, boca y ojo secos sin SS (BO), n = 13, y con SS n = 23. Material y métodos: Para la citología exfoliativa se utilizó cepillo recolector de células (Citobrush) deslizándolo a lo largo de la lámina de vidrio, fijándose posteriormente en etanol al 95%. En citologías por impresión se utilizó papel de acetato de celulosa (Milipore Hawp 304®), en tiras de un cm de longitud colocadas sobre la superficie de la mucosa bucal sobre el surco vestibular superior inmovilizando el papel y presionando por tres segundos. Se tiñeron con técnica de Papanicolau (PAP). Se valoró la morfología e histomorfometría, estudiando: área citoplasmática (AC), área nuclear (AN), relación núcleo-citoplasma (N:C) y cantidad de células por milímetro cuadrado (mm2). Resultados: Ambas técnicas nos permitieron observar en C: células epiteliales pavimentosas aisladas, basófilos, núcleos centrales normales, 20 a 30 por mm2, relación N/C 1:8. En el grupo BO: células aisladas, agrupadas y plegadas, con citoplasma a predominio eosinófilo, aumento de la cantidad de células 40 por mm2, relación núcleo-citoplasma relación N/C 1:4. En los pacientes SS se observó el área nuclear con cromatina más densa, 400 células por mm2, y relación N/C 1:2 en relación a BO y C. Hubo diferencias estadísticamente significativas entre los grupos en todas las características estudiadas. Conclusión: Podríamos inferir que la citología por impresión puede ser utilizada en el diagnóstico de lesiones orales y sistémicas en pacientes con hiposalivación.

Abstract The aim of the present research project was to compare two techniques for oral cytology study (exfoliative cytology and impression cytology) in order to assess changes in oral mucosa which might allow non -invasive diagnosis of Sjögren's syndrome cases (SS). Patients: 50 patients were selected, patients were paired by age and gender, and had been diagnosed with Sjögren's syndrome according to criteria of the American-European Consensus. Patients were distributed into the following three experimental groups: healthy control group (C), n = 14, Dry mouth and eyes group without SS, (ME) n = 13, and SS group n = 23. Material and methods: A cell harvesting brush (Cytobrush) was used for the exfoliative cytology procedure, sliding it along a glass plate and later fixating harvested cells in 95% ethanol. Cellulose acetate paper (Millipore Hawp 304®) was used for the impression cytology procedure. The paper was in 1 cm long stripes which were placed on the oral mucosa surface above upper vestibular groove; stripes were immobilized and pressure was applied for three seconds. Papanicolau (PAP) technique was used for dyeing. Morphology and histomorphology were assessed studying the following: cytoplasmic area (CA), nuclear areas (NA) nucleus-cytoplasm relationship (N:C) and amount of cells per square millimeter (mm2). Results: Both techniques revealed the following in C: isolated single-layered epithelial cells, basophils, normal central nuclei, 20 to 30 per mm2, N:C ratio 1:8. In the eye and mouth group (EM): grouped and folded isolated cells, cytoplasm with eosinophilic predominance increase of cell amount to 40 per mm2, nucleus-cytoplasm relationship N/C 1:4. SS patients showed the following: nuclear area with denser chromatin, 400 cells per mm2, and 1:2 N/C relationship with respect to mouth and ears and control. Statistically significant differences wereobserved among groups in all studied characteristics. Conclusion: We can infer that impression cytology can be used in systemic and oral lesion's diagnosis in patients afflicted with hyposalivation.

Study on the Changes in Distributions and Expressions of Aquaporin5 (AQP5) in Salivary Glands of Mice After Alcohol Ingestion

Alcohol intake is known to affect various organs in the human body, causing reduction of salivation in the oral cavity. Hypo-salivation effect of alcohol is a common feature, but the mechanism in salivary glands is still poorly studied. Therefore, in this study, the changes in salivary secretion and water channel protein (aquaporin5, AQP5) in salivary glands of mice were investigated after ethanol administration. Animals were divided in to 4 groups with the control, 4 g/kg ethanol, 8 g/kg ethanol and 16 g/kg ethanol administration groups. One hour after ethanol administration, saliva was collected from the oral cavity, and the animals were killed and parotid and submandibular glands were extracted to analyze the histopathology, AQP5 immunihistochemistry and AQP5 protein level. According to the results, the salivation rate decreased irrespective of the ethanol dose in mice, and viscosities increased with increase in ethanol dose. However, there were no pathological changes in parotid and submandibular glands due to ethanol administration. Expression of AQP5 in parotid and submandibular glands decreased with increase ethanol administration These results indicate that the reduction of salivary secretion due to acute alcohol intake is closely related to decrease of the water channel protein such as AQP5 in parotid glands and submandibular glands, rather than the damage of salivary glands.

Terapia farmacológica y avances terapéuticos en xerostomía e hiposalivación / Pharmacological therapy and therapeutic advancesin xerostomy and hyposalivation

La saliva juega un rol determinante en el mantenimiento y función de los tejidos orales, donde un decremento en los niveles del flujo salival conllevan a una hiposalivación o hiposialia, trayendo consigo una serie de características que propician un ambiente ideal para la instalaciónde microorganismos oportunistas y condiciones nocivas para la saludoral y sistémica de los pacientes. Hoy en día existen múltiples causas que conllevan a una hiposialia, entre ellas el síndrome de Sjõgren, la radioterapia de haz externo, entre otras, los cuales se han puesto a prueba mediante sialogogos farmacológicos como pilocarpina, cevimelina, betanecoly carbacolina, además de alternativas terapéuticas para revertir los signos obtenidos por la hiposalivación y mitigar los síntomas de xerostomía. El objetivo del presente es realizar una revisión de literatura sobre el tratamiento farmacológico en hiposalivación y xerostomía ensíndrome de Sjõgren y radioterapia de haz externo.

Saliva plays a determinant role in the maintenance and function of oral tissues, where a decrease in salivary flow levels leads to hyposalivation or hyposialia, bringing with it a series of characteristics that provide anideal environment for the installation of opportunistic microorganisms and conditions harmful to the oral and systemic health of patients.Today there are many causes that lead to hyposialia, including Sjögren’ssyndrome, external beam radiotherapy, among others, which have beentested by pharmacological sialogogs such as pilocarpine, cevimelin, betanecol and carbacoline, in addition to therapeutic alternativesto reverse the signs obtained by hyposalivation and to mitigate the symptoms of xerostomia. The objective of the present is to make a reviewof the literature on the pharmacological treatment in hyposalivation and xerostomia in Sjögren’s syndrome and external beam radiotherapy.

Características salivales y estado sistémico de sujetos con xerostomía / Salivary characteristics and systemic status of subjects with xerostomia

RESUMEN: Xerostomía o sensación de boca es una afección que afecta severamente la calidad de vida de quienes la padecen. Si bien se relaciona con la reducción del flujo salival (hiposalivación), existe evidencia contradictoria y se sugiere evaluar características cualitativas salivales y estado sistémico de los afectados para comprender su etiología y mejorar terapias asociadas. El objetivo de este estudio fue comparar pH y concentración de proteínas en saliva y estado sistémico entre sujetos xerostómicos con y sin hiposialia. Se midió pH, concentración de proteínas salivales y se consignaron antecedentes sistémicos y uso de fármacos en 27 individuos xerostómicos, que fueron divididos en hiposiálicos y no hiposiálicos. Se compararon las variables mencionadas usando test no paramétrico de Mann-Whitney y test Chi-Cuadrado. Se aceptaron diferencias estadísticamente significativas con error alfa igual o menor a 5 %. Sujetos xerostómicos con hiposialia presentaron mayor prevalencia de Artritis Reumatoide y Síndrome de Sjögren en comparación con xerostómicos sin hiposialia. No se encontraron diferencias estadísticamente significativas en relación a pH, concentración de proteínas y uso de medicamentos, variables que no influirían en el padecimiento de xerostomía, independiente de la existencia de hiposialia. Sujetos con xerostomía e hiposialia presentan mayor frecuencia de Artritis Reumatoide y Síndrome de Sjögren.

ABSTRACT: Xerostomia or mouth feeling is a condition that severely affects the quality of life of thosewho suffer from it. Although it is related to the reduction of salivary flow (hyposalivation),there is contradictory evidence and it is suggested to evaluate qualitative salivarycharacteristics and systemic state of those affected in order to understand its etiology and improve associated terapies. The objective of this study was to compare saliva, pH and protein concentration and systemic status among xerostomic subjects with and without hyposialia. Were measured PH and protein concentration and were recorded systemic antecedents and drug use in 27 xerostomic individuals, who were divided into hyposalic and nonhyposalic individuals. The mentioned variables were compared using non-parametric Mann-Whitney test and Chi-Square test. Statistically significant differences were accepted with alpha error equal to or less than 0.05%. Xerostomic subjects with hyposialia presented higher prevalence of Rheumatoid Arthritis and Sjögren's Syndrome compared to xerostomics without hyposialia. No statistically significant differences were found in relation to pH, protein concentration and drug use, variables that would not influence xerostomia, independent of hyposialia. Subjects with xerostomia with hyposialia present a higher frequency of Rheumatoid Arthritis and Sjögren's Syndrome.

Salivary stimulation by prolonged release of pilocarpine in sjõgren’ syndrome

Introduction: Prolonged drug delivery in the oral cavity offers many advantages, such as reducing adverse effects. Pilocarpine is an FDA-approved parasympathomimetic drug for the treatment of glandular hypofunction; however, its adverse effects limit its use. Objective: To evaluate the stimulation of salivary flow by the use of pilocarpine-releasing films, as well as their effects on the symptoms of xerostomia and adverse effects in patients with Sjõgren’s syndrome (SS). Materials and methods: Hydroxypropylmethylcellulose (Methocel K4MCR) films were prepared in 1 percent acetic acid and pilocarpine was added under magnetic stirring. The pH and thickness, as well as diffusion uniformity and kinetics of drug release per cm2 were evaluated by spectrophotometry. The films were tested sublingually in 40 patients with Sjõgren’s syndrome for a period of two weeks. Changes in their salivary flow were evaluated by analyzing samples of total saliva. Additionally, patients were screened for symptoms of xerostomia and adverse effects. Results: The films had a pH of 2.91 +/- 0.035, a thickness of 0.06866 +/- 0.00152μm, and a diffusion uniformity of 91 percent per cm2. Use of the films resulted in an increase in salivary flow in both primary and secondary Sjõgren’s syndrome, but this increase was only significant in primary SS. Conclusion: Films showed optimal physicochemical properties for their administration, and proved effective in stimulating salivary flow without causing adverse effects during their administration.

La saliva: una mirada hacia el diagnóstico / Saliva: a look on diagnosis

La saliva juega un importante rol en la prevención y mantenimiento de la salud oral. La alteración del flujo salival es un factor clave en el desarrollo de diversas patologías e infecciones oportunistas en lacavidad bucal. Existen diversos caminos por los que algunos elementosque no son constituyentes y habituales de la saliva pueden llegar a ella, a través de rutas intracelulares y extracelulares; gracias a esta posibilidad, se abre una perspectiva para su aplicación en el diagnósticode determinadas patologías. El conocimiento de su composición y funciones ayudará a promoveren los profesionales una mayor conciencia del papel de la saliva en la prevención de patologías y mantenimiento de la salud oral.

Saliva plays an important role in the preventionand maintenance of oral health. Alterationof salivary flow is a key factor in the developmentof various diseases and opportunistic infectionsin the oral cavity.There are various way by which some elementsthat are not common constituents of saliva canreach it through intracellular and extracellularroutes; thanks to this possibility, a prospectfor application in the diagnosis of certainpathologies opens. The knowledge of itscomposition and functions, help promoteprofessionals, greater awareness of the roleof saliva in the prevention of diseasesand maintenance of oral health.

cGVHD-Related Caries and Its Shared Features with Other 'Dry-Mouth'-Related Caries

Several systemic diseases and their medical treatment may predispose the development of aggressive dental caries. Head and neck radiotherapy, chemotherapy, Sjögren's syndrome and long-standing treatment with drugs that induce hyposalivation are some of these conditions. The aim of this article is to describe the clinical features of five patients who developed chronic graft-versus-host-disease (cGVHD) as a complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT) and, in spite of close dental follow-up, subsequently developed rampant caries. In these cases, the restorations showed early failure and the caries still progressed until generalized teeth destruction. The majority of the teeth therefore had to be extracted due to advanced dental caries and rapid clinical progression. Herein the term "cGVHD-related caries" is proposed to describe this under-recognized complication of cancer treatment that may evolve in allo-HSCT recipients that develop cGVHD. This condition is poorly recognized in the literature and may represent the final result of the clustering of oral complications in cGVHD patients, including mucositis, oral pain, hyposalivation, taste loss and oral infections, leading to rampant caries due to impaired oral hygiene and increased intake of highly cariogenic food. Consequently, the knowledge of this oral complication should improve the medical and dental management of cGVHD oral manifestations and improve the quality of life of patients with this post allo-HSCT complication.

Diversas doenças sistêmicas e seus tratamentos podem predispor ao desenvolvimento de cáries dentárias agressivas. A radioterapia de cabeça e pescoço, quimioterapia, síndrome de Sjögren e tratamentos prolongados com as drogas que induzem a hipossalivação são algumas destas condições. O objetivo deste artigo é descrever as características clínicas de cinco pacientes que desenvolveram doença do enxerto contra hospedeiro crônica (DECHc) como uma complicação do transplante alogênico de células-tronco hematopoiéticas (aloTCTH) e, apesar do acompanhamento periódico com dentistas, desenvolveram cáries rampantes. Nestes casos relatados, as restaurações mostraram falhas precoces e as cáries continuaram progredindo até a destruição generalizada dos dentes. A maioria dos dentes, portanto, foi extraída devido à cárie avançada e rápida progressão clínica. Neste artigo, o termo "cáries relacionadas à DECHc" é proposto para descrever esta complicação pouco conhecida do tratamento do câncer, que se manifesta em receptores de TCTH que desenvolvem DECHc. Esta condição é pouco reconhecida na literatura e pode representar o resultado final do agrupamento das complicações bucais em pacientes com DECHc, incluindo mucosite, dor oral, hipossalivação, perda de paladar e infecções orais, levando à cárie rampante devido à dificuldade de higiene oral e aumento da ingestão de alimentos altamente cariogênicos. Por consequência, o conhecimento desta complicação oral deve melhorar os tratamentos médico e odontológico das manifestações bucais da DECHc e melhorar a qualidade de vida dos pacientes com esta complicação após o TCTH.

Salivary stimulation by prolonged release of pilocarpine using films in diabetic rats / Estimulación salival mediante biopelículas de liberación prolongada de pilocarpina en ratas diabéticas

The local use of prolonged drug delivery in the oral cavity provides many advantages, i.e., it increases pharmacologic actions in the desired local site, allows smaller doses and reduces adverse effects. Pilocarpineis a cholinergic drug approved by the FDA for treating glandular hypofunction; however, the adverse effects associated with it limit its use. Objective: To evaluate cytotoxicity of films in adherent fibroblasts and their ability to release pilocarpine in vivo for a prolonged time in the oral cavity of diabetic rats and its effect on salivary flow. Methods: Chitosan and Hydroxypropylmethylcellulose (Methocel K4MCR) films were prepared in 1 percent acetic acid and pilocarpine was added under magnetic stirring. Cytotoxicity of films was evaluated in adherent fibroblasts HS27 and assessed by neutral red technique. The sialogogue effect of films was evaluated on the floor of the mouth of diabetic rats. Later, histopathological analysis was performed using hematoxylin and eosin and Masson’s trichrome stains. Results: Films were biocompatible and had 96 percent cell viability. It was possible to increase stimulation of salivary flow in diabetic rats (6.36+/-0.987mg/hr) compared to the control group (0.5+/-0.06mg/hr). The histopathological analysis did not show inflammatory infiltrate in the area where films were placed. Conclusion: Films were biocompatible and had high cell viability. Also, they considerably increased salivary flow in diabetic rats, without triggering an inflammatory infiltrate in the area which indicates that it is a biocompatible product for sustained release and safe for pilocarpine administration...

El uso local de administración prolongada de fármacos en la cavidad oral proporciona múltiples ventajas, aumentando la acción farmacológica en el sitio de acción, reducción de la dosis usual y disminución de los efectos adversos. La pilocarpina es una droga aprobada por la FDA para el tratamiento del deterioro de las glándulas salivales, sin embargo sus efectos adversos limitan su uso. Objetivo: Evaluar la citotoxicidad de las biopelículas en fibroblastos adherentes y su capacidad in vivo de liberar pilocarpina prolongadamente en la cavidad oral de ratas diabéticas y su efecto en el flujo salival. Metodología: Se elaboraron biopelículas de Quitosán y HPMC (Methocel K4MCR) adicionadas con pilocarpina en una solución de ácido acético 1 por ciento. Fue evaluada la citotoxicidad de las biopelículas en fibroblastos adherentes HS27 mediante la técnica de rojo neutro, además de ser evaluado el efecto sialogogo de las biopelículas en el piso de boca en ratas diabéticas Wistar, realizando después un análisis histopatológico de la zona de colocación, mediante la tinción de Hematoxilina y Eosina y Tricrómico de Masson. Resultados: Las biopelículas resultaron ser biocompatibles con un 96 por ciento de viabilidad celular. Se logró aumentar la estimulación del flujo salival en las ratas diabéticas (6.36+/-0.987 mg/hr), a comparación del grupo control (0.5+/-0.06 mg/hr). El análisis histopatológico no reveló un infiltrado inflamatorio presente en la zona de aplicación de las biopelículas. Conclusión: Las biopelículas resultaron biocompatibles con alta viabilidad celular, además que lograron aumentar considerablemente el flujo salival en ratas diabéticas, sin desencadenar un infiltrado inflamatorio en la zona de aplicación, indicando que es un producto de liberación prolongada biocompatible y seguro para la administración de pilocarpina...

Physicochemical and antimicrobial evaluation of chitosan and hydroxypropyl methylcellulose films forprolonged release of pilocarpine / Evaluación fisico-química y antimicrobiana de biopelículas de quitosán e hidroxipropilmetilcelulosa para liberación prolongada de pilocarpina

The use of prolonged local drug delivery to the oral cavity offers multiple benefits, such as increasing the pharmacological action in the desirable local site and reducing the usual dose and the adverse effects. Pilocarpine is a cholinergic drug approved by the FDA for the treatment of glandular hypofunction; however, the extent of its adverse effects limits its use. Objective: The main aim of this study was to analyze the physical and chemical properties of films, including pH, thickness, solubility, consistency and the ability to release pilocarpine for a prolonged time. Additionally, theantimicrobial activity in two opportunistic pathogens in hyposialia (Streptococcus mutans and Candida albicans) was also assessed. Methodology: Chitosan and HPMC (Methocel K4M CR) films were prepared in 1 percent acetic acid and pilocarpine was added under magnetic stirring. PH, thickness and time of solubility in artificial saliva, as well as diffusion and drug release kinetics per cm2 (OD=420nm) were assessed by spectrophotometry. The antimicrobialactivity was tested by disk diffusion test against St. mutans ATCC 700610 and C. albicans ATCC 90029 at concentrations of hyposalivation (1.44x1.2x106 CFU and 103 CFU, respectively). Results: All the films, except for Hydroxypropyl methylcellulose / Pilocarpine formulation, were found to have optimal physical-chemical properties for handling, maintaining drug diffusion in 76 percent per cm2 for four hours extended-release without showing antimicrobial activity at concentrations of hyposalivation. Conclusion: The films had optimum handling properties and a constant drug release; however, antimicrobial activity was not found...

El uso local de administración prolongada de fármacos en la cavidad oral proporciona múltiples ventajas, aumentando la acción farmacológica en el sitio local deseable, reducción de la dosis usual y disminución de los efectos adversos. La pilocarpina es una droga colinérgica aprobada por la FDA para el tratamiento de la hipofunción glandular, sin embargo la amplitud de sus efectos adversos limitan su uso. Objetivo: Con el objetivo de analizar las propiedades físico-químicas de las biopelículas se evaluó el pH, grosor, solubilidad, uniformidad y la capacidad de liberar prolongadamente pilocarpina, así como su actividad antimicrobiana ante los dos microorganismos patógenos oportunistas en la hiposialia (Streptococcus mutans y Candida albicans). Metodología: Se elaboraron biopelículas de Quitosán e Hidroxipropilmetilcelulosa (Methocel K4MCR) en ácido acético al 1 por ciento, adicionadas con pilocarpina bajo agitación magnética, evaluando el pH, grosor y el tiempo de solubilidad en saliva artificial, así como la uniformidad de difusión y cinética de liberación de la droga por cm2 mediante espectrofotometría (OD=420nm). Mediante difusión en disco se evaluó la actividad antimicrobiana ante Streptococcus mutans ATCC 700610 y Candida albicans ATCC 90029 en concentraciones encontradas en hiposalivación (1.44 x 106 UFC y 1.2 x 103 UFC respectivamente). Resultados: Todas las biopelículas, a excepción de la formulación Hidroxipropilmetilcelulosa e Hidroxipropilmetilcelulosa/ Pilocarpina resultaron tener las propiedades físico-químicas óptimas de manipulación, manteniendo una uniformidad de difusión de la droga en 76 por ciento por cm2 con liberación prolongada por 4 horas, sin mostrar actividad antimicrobiana en concentraciones de hiposalivación. Conclusión: Las películas obtuvieron las propiedades óptimas de manipulación, y una constante liberación del fármaco, sin embargo, ninguna formulación presentó actividad antimicrobiana...

Factors associated to salivary flow alterations in dry mouth female patients / Fatores associados a alterações no fluxo salivar em pacientes com xerostomia

BACKGROUND AND OBJECTIVES: Saliva plays an important role in oral health; it is involved in lubrication of the oral mucosa, protection against infections, transport of nutrients and digestive enzymes, remineralization of teeth, as well as aiding in chewing, swallowing and speech. Reductions in the amount of saliva are known to increase the risk of oral diseases. This study investigated the factors associated to salivary flow alterations and its relationship with age, burning mouth syndrome, psychiatric and sleep disorders, systemic diseases and chronic drug use. METHODS: A total of 30 patients complaining of dry mouth without unbalanced systemic diseases were included. Questionnaires regarding socio-demographic data, xerostomia, burning mouth, depression and anxiety symptoms, and sleep disturbances were applied. Measures of salivary flow rates were obtained using spit method. Correlation of hyposalivation and quantitative data was determined using a multivariate regression model. RESULTS: The age range was 31-83 years, hyposalivation was correlated positively with sleep disorder (β=0.079, 95% CI, to 0,124) and negatively with burning mouth (β=-0.043, 95% CI, -0.083 to -0.002). CONCLUSION: These results provide evidences regarding the association between reduced salivary flow and burning mouth, sleep disorders and chronic use of psychotropic medicines, and we highlighted the important role of antidepressants on modulation of burning mouth sensation...

JUSTIFICATIVA E OBJETIVOS: A saliva tem um papel importante na saúde bucal; está envolvida na lubrificação da mucosa oral, na proteção contra infecções, no transporte de nutrientes e enzimas digestivas, na remineralização dentária e também auxilia na mastigação, deglutição e fala. Sabe-se que reduções na quantidade de saliva aumentam o risco de doenças bucais. Este estudo investigou os fatores associados a alterações no fluxo salivar e seu relacionamento com idade, síndrome de ardência bucal, distúrbios psiquiátricos e do sono, doenças sistêmicas e uso crônico de medicamentos. MÉTODOS: Foi incluído um total de 30 pacientes com queixa de xerostomia sem doenças sistêmicas desequilibradas. Foram aplicados questionários sobre dados sociodemográficos, xerostomia, ardência bucal, sintomas de depressão e ansiedade e distúrbios do sono. As medidas de fluxo salivar foram obtidas pelo método spit. A correlação entre hipo-salivação e dados quantitativos foi determinada por um modelo univariado de regressão. RESULTADOS: A idade various de 31;83 anos, hipo-salivação foi correlacionada positivamente com distúrbios do sono (β=0,079, 95% CI, 0,033 a 0,124) e negativamente com ardência bucal (β=-0,043, 95% CI, -0,083 a -0,002). CONCLUSÃO: Esses resultados trazem evidências sobre a associação entre fluxo salivar reduzido e ardência bucal, distúrbios do sono e uso crônico de psicotrópicos, e destacamos o importante papel dos antidepressivos na modulação da sensação de ardência bucal...

Sialometria: aspectos de interesse clínico / Sialometry: aspects of clinical interest

A saliva total é um complexo de secreções multiglandulares composto de fluido gengival, células epiteliais descamadas, microrganismos, produtos do metabolismo bacteriano, resíduos alimentares, leucócitos, muco da cavidade nasal e da faringe. A saliva possui diversas funções, incluindo reparação tecidual, tamponamento, proteção, digestão, gustação, ação antimicrobiana, manutenção da integridade do dente e sistema de defesa antioxidante. A redução do fluxo salivar (hipossalivação) é um distúrbio comum, e estima-se que cerca de 20% da população geral tenham esta alteração. A hipossalivação pode ser decorrente de diabetes mellitus, hipotireoidismo, desidratação, comprometimento do parênquima glandular por processos infecciosos, doenças granulomatosas ou condições autoimunes e inflamatórias (como a síndrome de Sjögren e a artrite reumatoide), radioterapia da região cefálica e/ou cervical, bem como pode estar associada a distúrbios do humor, efeitos adversos ocasionados pelo uso de algumas medicações ou, ainda, ser de causa idiopática. As terapias convencionais para o tratamento da redução do fluxo salivar, com o uso de sialogogos gustatórios e químicos, ainda apresentam restrições. Contudo, novas alternativas têm mostrado grande perspectiva no tratamento deste problema. Diagnosticar um paciente como hipossalivador crônico é um desafio na prática clínica, e os métodos de avaliação do fluxo salivar são pouco conhecidos pelos reumatologistas. A avaliação seriada do fluxo salivar é importante para o correto diagnóstico e prognóstico de determinadas condições bucais e sistêmicas. Esta revisão aborda alguns aspectos relacionados à função da saliva, às consequências da hipossalivação e aos métodos de medição da taxa de fluxo salivar, conceitos úteis na prática diária do reumatologista.

Whole saliva is a multiglandular secretion complex consisting of gingival fluid, desquamated epithelial cells, microorganisms, products of bacterial metabolism, food debris, leukocytes mucus from the nasal cavity and the pharynx. Saliva has many functions, including tissue repair, tamponage, protection, digestion, taste, antimicrobial action, maintaining tooth integrity and antioxidant defense system. A decrease in salivary flow (hyposalivation) is a common disorder and it is estimated that approximately 20% of the general population have this alteration. Hyposalivation may be due to diabetes mellitus, hypothyroidism, dehydration, impaired glandular parenchyma by infectious processes, granulomatous diseases or autoimmune and inflammatory conditions (such as Sjogren's syndrome and rheumatoid arthritis), radiotherapy of head and/or neck region, or it may be associated with mood disorders, adverse effects caused by the use of some medications or even be idiopathic. Conventional therapies for the treatment of reduced saliva flow with the use of chemical and gustatory secretagogues are still limited. However, new alternatives have shown great perspective in the treatment of this disorder. To diagnose a patient as having chronic hyposalivation is a challenge in clinical practice and methods of salivary flow assessment are little known by rheumatologists. The serial evaluation of salivary flow is important for the diagnosis and prognosis of certain oral and systemic conditions. This review addresses some aspects related to the role of saliva, the consequences of hyposalivation and methods of salivary flow rate measurement, useful concepts in the daily practice of rheumatology.

Profile of salivary gland flow dysfunctions in patients with differentiated thyroid carcinoma submitted to radioiodine therapy

AIM: To evaluate the effects of radioiodine therapy on salivary flow in patients with differentiated thyroid cancer. METHODS: A sample comprising 88 patients submitted to ablation with iodine 131 was included in the study. The patients were submitted to sialometry and evaluation of the presence of xerostomia before, 10 days and 3 months after radioiodine therapy. RESULTS: Xerostomia was observed in 36.4% of the patients before radioiodine therapy, 59.15% at 10 days after therapy, and 25% at 3 months after therapy. Significant differences were observed in non-stimulated salivary flow rates between the second and third evaluations (p<0.020) and in stimulated salivary flow between the first and second evaluations (p<0.010). CONCLUSIONS: The results suggest that changes in salivary flow resulting from radioiodine therapy are more pronounced during the first weeks after treatment and seem to regress after 3 months.

Human salivary gland stem cells ameliorate hyposalivation of radiation-damaged rat salivary glands

Salivary function in mammals may be defective for various reasons, such as aging, Sjogren's syndrome or radiation therapy in head and neck cancer patients. Recently, tissue-specific stem cell therapy has attracted public attention as a next-generation therapeutic reagent. In the present study, we isolated tissue-specific stem cells from the human submandibular salivary gland (hSGSCs). To efficiently isolate and amplify hSGSCs in large amounts, we developed a culture system (lasting 4-5 weeks) without any selection. After five passages, we obtained adherent cells that expressed mesenchymal stem cell surface antigen markers, such as CD44, CD49f, CD90 and CD105, but not the hematopoietic stem cell markers, CD34 and CD45, and that were able to undergo adipogenic, osteogenic and chondrogenic differentiation. In addition, hSGSCs were differentiated into amylase-expressing cells by using a two-step differentiation method. Transplantation of hSGSCs to radiation-damaged rat salivary glands rescued hyposalivation and body weight loss, restored acinar and duct cell structure, and decreased the amount of apoptotic cells. These data suggest that the isolated hSGSCs, which may have characteristics of mesenchymal-like stem cells, could be used as a cell therapy agent for the damaged salivary gland.

Clinical diagnosis of hyposalivation in hospitalized patients

OBJECTIVE: The aim of this study was to evaluate the effectiveness of clinical criteria for the diagnosis of hyposalivation in hospitalized patients. MATERIAL AND METHODS: A clinical study was carried out on 145 subjects (48 males; 97 females; aged 20 to 90 years). Each subject was clinically examined, in the morning and in the afternoon, along 1 day. A focused anamnesis allowed identifying symptoms of hyposalivation, like xerostomia complaints (considered as a reference symptom), chewing difficulty, dysphagia and increased frequency of liquid intake. Afterwards, dryness of the mucosa of the cheecks and floor of the mouth, as well as salivary secretion during parotid gland stimulation were assessed during oral examination. RESULTS: Results obtained with Chi-square tests showed that 71 patients (48.9%) presented xerostomia complaints, with a significant correlation with all hyposalivation symptoms (p <0.05). Furthermore, xerostomia was also significantly correlated with all data obtained during oral examination in both periods of evaluation (p<0.05). CONCLUSION: Clinical diagnosis of hyposalivation in hospitalized patients is feasible and can provide an immediate and appropriate therapy avoiding further problems and improving their quality of life.

Avaliação de fatores associados ao diagnóstico de queimação bucal: um estudo preliminar / Evaluation of factors associated to diagnosis of burning mouth: a preliminary study

Objetivo: avaliar fatores associados ao diagnóstico de ardência bucal como xerostomia, hipossalivação, sintomas depressivos, ansiedade, transtornos de sono, doenças sistêmicas e uso contínuo de medicamentos. Métodos: foram avaliados 22 pacientes atendidos em nível ambulatorial através de escalas validadas e questionário sociodemográfico, seguido de medidas de fluxo salivar espontâneo e estimulado através do método de expectoração salivar. Na análise estatística descritiva foi utilizado SPSS 16.0. Resultados: a amostra foi composta por 4 homens e 18 mulheres com idade média de 61,6+2,83 anos. As médias de fluxo salivar espontâneo e estimulado foram 0,27+0,06 ml/min e 0,84+0,08 ml/min, respectivamente. A hipossalivação esteve presente em 54,5% dos casos, sendo que a xerostomia foi referida por 31,3% dos pacientes. Sintomas depressivos leves foram observados em 22,7% da amostra. Na avaliação de ansiedade-traço 31,8% apresentaram sintomas de ansiedade moderada, 63,6%, sintomas de ansiedade elevada e 4,5%, ansiedade muito elevada. Quanto à avaliação de ansiedade-estado 27,3% apresentaram sintomas de ansiedade moderada e 72,7% sintomas de ansiedade elevada. Setenta e sete por cento apresentaram alterações de sono. Os exames sorológicos não apresentaram alterações significativas. Conclusão: estes resultados sugerem associação entre os parâmetros comportamentais avaliados e os sintomas bucais, sendo necessário o aumento da amostra para que possamos confirmar estatisticamente essa tendência.

Aim: to evaluate factors associated with the diagnosis of burning mouth, such as dry mouth, hyposalivation, depressive symptoms, anxiety, sleep disorders, systemic diseases, and continuous use of medications. Methods: twenty-two patients recruited from outpatient clinics were assessed using validated scales and a sociodemographic questionnaire. Patients’ spontaneous and stimulated salivary flow rates were also measured using saliva expectoration. SPSS 16.0 was used in the descriptive statistical analysis. Results: the sample consisted of 4 men and 18 women whose mean age was 61.6±2.83 years. The mean of spontaneous and stimulated salivary flow rates were 0.27+0.06 mL/min and 0.84+0.08 mL/min, respectively. Hyposalivation was present in 54.5% of cases, and dry mouth was reported by 31.3% of patients. Mild depressive symptoms were observed in 22.7% of the sample. When assessing anxiety-trait, we found that 31.8% had moderate symptoms of anxiety, 63.6% had symptoms of high anxiety, and 4.5% had very high anxiety. The assessment of anxiety-status showed that 27.3% and 72.7% had moderate and elevated anxiety symptoms, respectively. Seventy-seven percent had sleep disorders. Serological tests showed no significant changes. Conclusion: Our findings suggest an association between the behavioral parameters evaluated and the oral symptoms, indicating the need for a larger sample to confirm this trend using statistical analysis.