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.

Clinical and Histological Effects of Calcium Hydroxyapatite Filler in the Orofacial Region: A Study in Rats.

BACKGROUND: Calcium hydroxyapatite (CaHA) dermal filler has been increasingly used in facial aesthetic procedures. OBJECTIVE: To investigate clinical and histological changes associated with calcium hydroxyapatite (CaHA) dermal filler in the orofacial region. MATERIALS AND METHODS: Forty-eight female Wistar rats were divided into CaHA and control groups. The material was applied in the ventral tongue and the submandibular region; the animals were euthanized after 7, 30, and 90 days. RESULTS: After 7 days, yellowish nodules with a firm consistency were observed on the tongue. In 2 animals, the material migrated to the base of the tongue. Histopathological examination revealed CaHA spheres surrounded by an infiltrate, predominantly composed of macrophages. In the CaHA group, the percentage of collagen in the tongue and dermis was higher compared with the control group ( p < .05) at both 30 and 90 days. The thickness of the epidermis/dermis was also higher in the CaHA group ( p < .05). In 5 submandibular glands containing material, areas of edema and hyperemia were observed, along with infiltrates of neutrophils, lymphocytes, and plasma cells. Changes in the morphology of ducts and acini in adjacent regions were evident. CONCLUSION: CaHA exhibits satisfactory properties for filling and collagen biostimulation in the tested regions. Further studies are required to explore the potential for migration and the glandular alterations.

Chronic Sclerosing Sialadenitis of the Submandibular Gland and its Histopathological Spectrum in the IgG4-Related Disease: a Series of 17 Cases.

PURPOSE: This study aimed to characterize the histopathological immunohistochemical features of chronic sclerosing sialadenitis, emphasizing the IgG4-related disease. METHODS: Seventeen cases of chronic sclerosing sialoadenitis were examined for histopathological aspects, (inflammation, fibrosis, glandular parenchyma, and lymphoid follicles) and immunohistochemistry (BCL2, CD3, CD20, CD34, CD163, p63, cyclin D1, mast cell, SMA, S100A4, IgG, and IgG4) which were scored. IgG4-related disease features were investigated. Demographic and clinical data were also collected. RESULTS: Males predominated (10:7), with an average lesion size of 3.9 cm. Common histopathological findings included reduced acinar parenchyma, lymphoid follicle formation, and ductular proliferation. CD3-positive T lymphocytes and CD34- and SMA-positive stromal fibroblasts were abundant. Nine cases (53%) showed sialoliths and three cases met the criteria for IgG4-related disease. CONCLUSION: CSS of the submandibular gland represents a reactive pattern rather than IgG4-RD as only 3 cases seemed to be related to IgG4-RD. The immunohistochemical profile revealed an abundant population of CD3-positive T lymphocytes, as opposed to regulatory proteins such as cyclin D1, demonstrating that populations of CD34- and SMA-positive stromal fibroblasts contribute to the fibrosis characteristic of CSS. In addition, our results provide a comprehensive insight into the study of CSS and its relationship with IgG4-RD.

Primary intestinal-type adenocarcinoma: Report of a rare case involving a young patient.

The aim of this report was to describe a rare example of sporadic intestinal-type adenocarcinoma of the major salivary glands and oral cavity. A 23-year-old female patient presented an asymptomatic, progressive-growing mass involving the floor of mouth and the left submandibular gland. Fine-needle aspiration cytology, imaging exams, and surgical specimen findings were consisted with the diagnosis of primary intestinal-type adenocarcinoma, despite its similar immunohistochemical results with colorectal adenocarcinoma. Adjuvant chemotherapy and radiotherapy were performed, but the patient developed multiple metastatic lesions after one year of initial the intervention and deceased following 13 months of follow-up, despite several therapeutic efforts. We verified that sporadic cases of primary intestinal-type adenocarcinoma still lack information regarding etiology and tumorigenesis, especially in young and females. A complete diagnostic workflow is indispensable to rule out the presence of primary colorectal adenocarcinoma.

Lymphomas affecting the submandibular glands.

BACKGROUND: Lymphomas affecting the submandibular glands are very uncommon and few reports are currently available in the literature. Therefore, the aim of the current study is to describe the clinical and microscopic features of an original series of lymphomas affecting the submandibular glands. MATERIAL AND METHODS: The pathology files of two institutions were searched for lymphoma cases affecting the submandibular glands. The original hematoxylin and eosin, and immunohistochemical slides were revised by a pathologist for diagnosis confirmation following the revised 4th edition of the World Health Organization classification of tumours of haematopoietic and lymphoid tissues. Clinical data regarding age, sex, clinical manifestation, treatment, follow-up and status at last appointment were retrieved from the patients' medical charts. RESULTS: During the period investigated, 16 cases were included in the study. Females predominated (10:6) with a mean age of 57.8 years-old. Tumors usually presented as asymptomatic swellings. MALT lymphoma represented the most common subtype, followed by diffuse large B cell lymphoma and follicular lymphoma. Three patients died, one of them affected by plasmablastic lymphoma, one by DLBCL and one by MALT lymphoma. CONCLUSIONS: Low-grade B cell lymphomas predominate in the submandibular glands, but DLBCL and other subtypes may also be rarely diagnosed in this salivary gland.

Is the neutrophil-to-lymphocyte ratio a marker for differentiating between benign and malignant submandibular gland masses?

OBJECTIVE: This study aimed to evaluate the effect of the neutrophil-to-lymphocyte ratio on the differentiation of benign and malignant masses in the submandibular triangle. METHODS: We retrospectively evaluated 48 patients who underwent surgery for submandibular gland masses between January 2013 and February 2023. The patient's age, gender, preoperative complete blood count and imaging findings, postoperative histopathological diagnosis, and hemogram data were analysed. Patients were evaluated according to their postoperative histopathological diagnoses and categorised into four main groups: sialolithiasis, sialadenitis, benign tumours, and malignant tumours. Benign submandibular gland disease formations were evaluated under group B and malignant tumour formations under group M. RESULTS: A preoperative fine needle aspiration biopsy was performed on 19 patients due to sialadenitis, pleomorphic adenoma, and malignant diseases other than sialolithiasis. One patient died among the patients with malignant disease and the remaining 7 patients were compared with the benign group of 40 patients regarding preoperative and postoperative neutrophil-to-lymphocyte ratio. In the benign group, the neutrophil-to-lymphocyte ratio was 2.64 preoperatively and decreased to 2.34 in the first postoperative year. The preoperative neutrophil-to-lymphocyte ratio decreased from 4.79 to 1.77 postoperatively in the malignant group. A statistically significant difference was observed (p<0.05). CONCLUSION: This is the first study to demonstrate that the neutrophil-to-lymphocyte ratio can be used as a biomarker in submandibular gland masses and has prognostic significance in malignant masses. In addition to fine needle aspiration biopsy results, neutrophil-to-lymphocyte ratio can be used as a biomarker.

Enfermedad de Castleman unicéntrica, una causa infrecuente de masa cervical / Unicentric Castleman disease, an infrequent cause of cervical mass

La enfermedad de Castleman (EC) describe una serie de desórdenes linfoproliferativos de patrones histológicos similares, pero de etiologías, presentaciones clínicas y enfrentamientos notoriamente variables. Se presenta el caso de un paciente que consultó por masa cervical, cuyo estudio final concluyó EC unicéntrica, la cual se resolvió de forma quirúrgica. Además, se presenta una revisión actualizada del tema, con foco en la enfermedad unicéntrica.

Castleman's disease (CD) describes several lymphoproliferative disorders with similar histological patterns, but with notoriously variable etiologies, clinical presentations, and management. We present the case of a patient who consulted with cervical mass, whose final study concluded with unicentric CD, which was treated surgically. In addition, an updated review of the subject is presented, focusing on unicentric disease.

Maternal Fluoride Exposure Exerts Different Toxicity Patterns in Parotid and Submandibular Glands of Offspring Rats.

There is currently a controversial and heated debate about the safety and ethical aspects of fluoride (F) used for human consumption. Thus, this study assessed the effects of prenatal and postnatal F exposure of rats on the salivary glands of their offspring. Pregnant rats were exposed to 0, 10, or 50 mg F/L from the drinking water, from the first day of gestation until offspring weaning (42 days). The offspring rats were euthanized for the collection of the parotid (PA) and submandibular (SM) glands, to assess the oxidative biochemistry and to perform morphometric and immunohistochemical analyses. F exposure was associated with a decrease in the antioxidant competence of PA in the 10 mg F/L group, contrasting with the increase observed in the 50 mg F/L group. On the other hand, the antioxidant competence of the SM glands was decreased at both concentrations. Moreover, both 10 and 50 mg F/L groups showed lower anti-α-smooth muscle actin immunostaining area in SM, while exposure to 50 mg F/L was associated with changes in gland morphometry by increasing the duct area in both glands. These findings demonstrate a greater susceptibility of the SM glands of the offspring to F at high concentration in comparison to PA, reinforcing the need to adhere to the optimum F levels recommended by the regulatory agencies. Such findings must be interpreted with caution, especially considering their translational meaning.

Ethanol binge drinking during pregnancy and its effects on salivary glands of offspring rats: oxidative stress, morphometric changes and salivary function impairments.

OBJECTIVES: To investigate the biochemical and morphological effects of ethanol (EtOH) binge drinking during pregnancy on parotid glands (PG), submandibular glands (SMG), and saliva of offspring rats. METHODS: Pregnant Wistar rats (n = 8) were exposed to EtOH consumption (3 g/kg/day - 20 % w/v) for three consecutive days. The saliva of 40-day-old offspring rats was collected to determine amylase activity and total protein concentration. PG and SMG were collected to performe oxidative biochemistry, morphometric and immunohistochemistry analyses (Student's t-test, p < .05). RESULTS: EtOH consumption during pregnancy significantly decreased the total protein concentration and decreased amylase activity. In the PG, the EtOH group showed increased lipid peroxidation and decreased antioxidant capacity against peroxyl. In the SMG, the EtOH group showed increased lipid peroxidation and NOx metabolite levels. PG exposed to EtOH showed a decrease of acini, ducts, and total parenchymal area. SMG exposed to EtOH showed an increase in the total stromal area. The expression of CK-19 and Vimentin were found not different between groups. CONCLUSIONS: For the first time, a three-day EtOH binge-drinking protocol during pregnancy is associated with oxidative stress and morphometric alterations in the salivary glands of offspring rats and with the functional reduction of the main salivary enzyme (amylase). CLINICAL RELEVANCE: EtOH consumption during pregnancy altered the morphology and physiology of the salivary glands of offspring rats.

Retroauricular endoscope-assisted versus conventional submandibular gland excision for benign and malignant tumors.

BACKGROUND: Surgical scars are a significant cosmetic problem, especially when in exposed areas such as the anterior neck. To avoid or reduce visible scarring, diverse innovative surgical approaches to the neck have been introduced. The purpose of this study was to evaluate the feasibility and safety of the endoscopic resection using the retroauricular approach for submandibular gland excision. METHODS: The present study enrolled 48 patients who underwent conventional transcervical submandibular gland excision and 23 patients who underwent endoscope-assisted retroauricular approach submandibular gland excision, from February 2014 through February 2018 at the Department of Head and Neck Surgery and Otorhinolaryngology of the AC Camargo Cancer Center, in Sao Paulo, Brazil. The surgical outcomes were retrospectively reviewed. RESULTS: In the conventional group, 26 (54%) patients were male. The mean age was 49.3 years (range 22-81). Twenty-two patients (46%) had sialoadenitis; twenty-one (44%) had benign and five (10%) had malignant tumors. The mean total surgical time was 86.4 min (range 40-180), and the mean total length of hospital stay was 1.3 days. Twenty-seven (56%) patients suffered from local postoperative complications in the neck. In the retroauricular group, 14 (61%) patients were male. The mean age was 44.1 years (range 24-71 years). Seven patients (31%) had sialoadenitis, twelve (53%) had benign tumors and four (16%) had malignant tumors. The mean total surgical time was 86.4 min (range 75-300 min), and the mean total length of hospital stay was 1.2 days. Twelve (53%) patients suffered from local postoperative complications in the neck. No surgical site infections or systemic complications were described. CONCLUSIONS: The retroauricular endoscopic-assisted submandibular gland resection is feasible, with excellent cosmetic results and no significant complication rate increase, and can be a safe potential surgical alternative for patients who are motivated to avoid a visible neck scar.

Adenoma pleomorfo de la glándula submandibular: reporte de un caso y revisión de la literatura / Pleomorphic adenoma of the submandibular gland: report of a case and review of literature

Los tumores de las glándulas salivales constituyen alrededor de 5% de las neoplasias de cabeza y cuello. El adenoma pleomorfo es el tumor benigno más frecuente de las glándulas salivales, representa aproximadamente 60% de todas las neoplasias salivales, está compuesto fundamentalmente por una proliferación de células mioepiteliales y por un amplio espectro de componentes de tejido epitelial y mesenquimal, rodeado por una nítida cápsula fibrosa. Alrededor de 80% de los adenomas pleomorfos aparecen en la parótida, 10% en la glándula submandibular y 10% en las glándulas salivales menores de la cavidad oral. La edad media de presentación es a los 46 años, pero la edad oscila entre la tercera y la quinta década de la vida. No obstante, ha sido encontrado en individuos de todas las edades, presentando una ligera predilección por el sexo femenino. Respecto a su sitio de origen, el adenoma pleomorfo es asintomático, de crecimiento lento y consistencia firme. La tomografía axial computarizada (TAC) y la resonancia magnética nuclear (RMN) son de gran utilidad para evaluar la extensión de la lesión, así como el compromiso de estructuras importantes. La biopsia por aspiración con aguja fina (BAAF) es un método útil para el diagnóstico de este tipo de neoplasias. El tratamiento de este tipo de lesiones consiste en la remoción quirúrgica de la tumoración junto con la glándula afectada. Menos de 1% de los casos de adenomas pleomorfos sufren transformación maligna, especialmente los que han presentado múltiples recidivas (AU)

The tumors of the salivary glands constitute about 5% of the neoplasms of the head and neck. The pleomorphic adenoma is the most frequent benign tumor of the salivary glands, represents approximately 60% of all salivary neoplasms, is composed mainly of a proliferation of myoepithelial cells and a wide spectrum of components of epithelial and mesenchymal tissue, surrounded by a sharp fibrous capsule. About 80% of pleomorphic adenomas appear in the parotid, 10% in the submandibular gland and 10% in the minor salivary glands of the oral cavity. The average age of presentation is 46 years, but age ranges between the third and fifth decade of life. However, it has been found in individuals of all ages, presenting a slight female predilection. Regarding its site of origin, the pleomorphic adenoma is asymptomatic, slow growing and firm consistency. Computed tomography (CT) and nuclear magnetic resonance (NMR) are very useful to evaluate the extent of the injury as well as the commitment of important structures. Fine needle aspiration biopsy (FNAB) is a useful method for the diagnosis of this type of neoplasm. The treatment of this type of injuries consists in the surgical removal of the tumor together with the affected gland. Less than 1% of cases of pleomorphic adenomas suffer malignant transformation, especially those that have presented multiple recurrences (AU)

Juvenile hemochromatosis with multi-organ involvement diagnosed at autopsy.

Hereditary hemochromatosis (HH) includes various disorders in iron metabolism producing iron deposits in several organs. HH is classified according to the HFE gene mutation. HH type I is characterized by HFE gene mutation, while types II, III and IV are due to other conditions. Juvenile hemochromatosis (JH) is related to hemojuvelin mutation, which is a regulatory peptide of the hepcidin protein, which regulates iron absorption. We report a case of JH and offer a concise review of the literature. A 14-year-old girl, with no secondary sexual characteristics, presented with abdominal pain, cough and dyspnoea. Clinical examination revealed right lower lobe consolidation, pleural effusion, cardiomegaly and an ejection fraction of 20%, with no response to treatment. On autopsy she was seen to have pleural and pericardial effusion, dilated cardiomyopathy, liver cirrhosis and pancreatic fibrosis. Prussian blue stain showed iron overload in these organs. JH with hypogonadism, cardiomyopathy and cirrhosis was diagnosed.

Tumores de glándula submandibular: experiencia clínica del Hospital Guillermo Grant Benavente / Submandibular gland tumors: clinical experience of Guillermo Grant Benavente Hospital

RESUMEN Introducción: Los tumores de la glándula submandibular son poco frecuentes. Representan menos del 1% de todos los tumores de cabeza y cuello. Corresponden al 10% de los tumores de las glándulas salivales. Aproximadamente el 50% son malignos. Objetivos: Analizar la experiencia clínica con las submandibulectomias realizadas en el Servicio de Otorrinolaringología y Cirugía de Cabeza y Cuello del Hospital Guillermo Grant Benavente. Material y método: Estudio descriptivo retrospectivo. Revisión de fichas clínicas de pacientes intervenidos de submandibulectomía entre el 01 de enero de 2011 y el 31 de diciembre de 2016 en nuestro servicio. Resultados: Se realizaron 28 submandibulectomías por patología tumoral. La edad promedio fue de 54 años, siendo el 71% de sexo femenino. 21 tumores fueron benignos (75%), siendo el más frecuente el adenoma pleomorfo (14 casos), y 7 tumores malignos (25%), siendo el más frecuente el carcinoma adenoidequístico. Se reportaron dos complicaciones transitorias (7%), una paresia de la rama marginal del nervio facial y una paresia del nervio hipogloso. El 42% de los tumores malignos presentó recurrencia. Conclusión: Nuestra serie presenta resultados acordes a la literatura en cuanto a edad de presentación, distribución por sexo, tipos histológicos, tasa de complicaciones y recurrencia; sin embargo, difiere en la menor frecuencia de tumores malignos, siendo en nuestra serie de 25%. Patología poco frecuente. La presencia de una masa indolora submandibular debe ser derivada a los centros de referencia para estudio y eventual resolución quirúrgica por el riesgo de malignidad.

ABSTRACT Introduction: Submandibular gland tumors are rare. They represent less than 1% of all head and neck tumors. They correspond to 10% of the tumors of the salivary glands. Approximately 50% are malignant. Aim: To analyze the clinical experience with the submandibulectomies performed in the Otorhinolaryngology and Head and Neck Surgery Service of the Guillermo Grant Benavente Hospital. Material and Method: Retrospective descriptive study. Review of clinical records of patients treated with a submandibulectomy between January 1,2011 and December 31, 2016 in our service. Results: 28 submandibulectomies were performed due to tumor pathology. The average age was 54 years, being 71% female. 21 tumors were benign (75%), being the most frequent the pleomorphic adenoma (14 cases), and 7 malignant tumors (25%), being the most frequent the adenoidequistic carcinoma. Two transient complications (7%) were reported, a paresis of the marginal branch of the facial nerve and a paresis of the hypoglossal nerve. 42% of malignant tumors presented recurrence. Conclusion: Our series presents results according to the literature regarding age of presentation, distribution by sex, histological types, complication rate and recurrence; however, it differs in the lower frequency of malignant tumors, being in our series of 25%. Uncommon pathology. The presence of a submandibular painless mass must be referred to the reference centers for study and possible surgical resolution due to the risk of malignancy.

Congenital dilatation of the submandibular duct.

Congenital dilatation of the submandibular duct also known as imperforate submandibular duct is a rare condition of unknown etiology, clinically characterized as a well-defined, fluctuant swelling in the floor of the mouth, and microscopically defined as a cystic cavity covered with pseudostratified columnar epithelium consistent with a dilated salivary duct. A 1-month-old female presented with a translucent, smooth cystic swelling in the floor of the mouth causing breastfeeding difficulty. The lesion was surgically excised and microscopically, a cystic cavity lined with pseudostratified columnar epithelium was observed. The final diagnosis was congenital dilatation of the submandibular duct. Dentists and otolaryngologists should consider congenital dilatation of the submandibular duct when evaluating fluctuant swelling in the floor of the month of infants.

Effect of low radiation dose on the expression and location of aquaporins in rat submandibular gland.

Head and neck cancers are common in several regions of the world and the treatment usually includes radiotherapy. This treatment can generate adverse effects to the salivary flow, with a relationship between the dose and the damage caused. Salivary gland cells are highly permeable to water and therefore, they express aquaporins (AQPs). This study analyzed changes in the expression and location of these proteins and identified morphological changes induced by low radiation in rat submandibular gland. Female rats were divided into control and irradiated groups. Immunohistochemistry analysis allowed confirming the presence of AQP1 in the blood vessel endothelium. Intense and steady labelling granules were also observed in the cytoplasm of submandibular gland ductal cells. In addition, there was AQP5 positive labelling in ductal cells delimiting the lumen of intercalated duct, in the cytoplasm and membrane of acinar cells. Finally, the decrease of AQP labelling in irradiated animal glands validated their radiosensitivity. Thus, the decrease in AQP1 protein levels in the endothelium and AQP5 in gland ductal cells of irradiated animals may have hindered the removal of water from the lumen of ductal cells, inducing a delay in water absorption and triggering a slight lumen increase.

Differential immunohistochemical expression of type I collagen and matrix metalloproteinase 2 among major salivary glands of young and geriatric mice.

OBJECTIVE: This study aimed to demonstrate the immunohistochemical changes associated with MMP-2 and type 1 collagen separately for the first time in the major salivary glands (the parotid, submaxillary, and sublingual glands) that occur with aging in mice. MATERIAL AND METHODS: Fourteen Balb/c white mice (50-80 g) were used in this study. The animals were divided into two equal groups. Group I consisted of young animals (2-month-old) (n=7) and Group II consisted of older animals (18-month-old) (n=7). After routine histological follow-ups, Hematoxylin-eosin (H&E), Masson's Trichrome staining and immunohistochemical staining was performed for type I collagen and MMP-2. RESULTS: We observed that there were age-related decreases in the number of acinar cells, increase in eosinophilic zymogen granules in cells, collagen accumulation in fibrotic areas and dilatation in interlobular ducts. Also, while type I collagen and MMP-2 immunoreactivity were moderate in the salivary glands of the young mice, they were high in the salivary glands of the old mice (p=0.001). In the H-score assessment, MMP-2 immunoreactivity was lower at a significant level in young mice than in old mice (p=0.001). CONCLUSIONS: This study showed that anatomical, physiological and morphological abnormalities occur in all three major salivary glands as a natural consequence of aging.

Elastographic ultrasound: an additional image tool in Sjögren's syndrome.

AIM: To evaluate the stiffness of parotid and submandibular glands using elastography ultrasound and to correlate it with B-mode ultrasonographical, clinical and serological features, salivary profibrotic and inflammatory chemokines, and salivary gland fibrosis. METHODS: We performed B-mode and elastography ultrasound of major salivary glands of 26 patients with primary Sjögren's syndrome. We registered the shear wave velocity (SWV) and correlated it with the morphologic ultrasonographic changes assessed by the Hocevar scale. We assessed the European League Against Rheumatism (EULAR) Sjögren's Syndrome Disease Activity Index (ESSDAI), EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI), non-stimulated whole salivary flow rate (NSWSF), C3 and C4 levels, anti-Ro/La antibodies, salivary inflammatory (C-X-C motif ligand 13 [CXCL13], CXCL10, CXCL8, C-C motif ligand 2 [CCL2], interleukin 10 [IL-10] and IL-6) and pro-fibrotic (CXCL14, CCL28, tumor necrosis factor-related apoptosis-inducing ligand and transforming growth factor ß) chemokines and cytokines and evaluated the presence of fibrosis in the minor salivary gland. RESULTS: Ninety-two percent of patients were women; mean age was 51.1 ± 11 years; median disease duration was 6.1 years; 92.3% had oral symptoms and 26.9% fibrosis. The median B-mode score was 22.2 points and the median SWV 2.5 m/s (τ = 0.53, P = 0.001). The SWV correlated with the NSWSF (τ = -0.53, P = 0.001), ESSDAI (τ = 0.31, P = 0.03), glandular ESDDAI domain (τ = 0.36, P = 0.02), C4 levels (τ = -0.32, P = 0.04), salivary CXCL13 (τ = 0.29, P = 0.03) and CXCL10 (τ = 0.30, P = 0.003), but not with age and fibrosis. CONCLUSION: WV correlated with the B-mode ultrasound score, systemic and glandular activity and in a large degree with CXCL10, an inflammatory chemokine, but not with fibrosis. An increased SWV might represent chronic glandular inflammation rather than fibrotic changes in these patients.

Differential immunohistochemical expression of type I collagen and matrix metalloproteinase 2 among major salivary glands of young and geriatric mice

Abstract Objective This study aimed to demonstrate the immunohistochemical changes associated with MMP-2 and type 1 collagen separately for the first time in the major salivary glands (the parotid, submaxillary, and sublingual glands) that occur with aging in mice. Material and Methods Fourteen Balb/c white mice (50-80 g) were used in this study. The animals were divided into two equal groups. Group I consisted of young animals (2-month-old) (n=7) and Group II consisted of older animals (18-month-old) (n=7). After routine histological follow-ups, Hematoxylin-eosin (H&E), Masson's Trichrome staining and immunohistochemical staining was performed for type I collagen and MMP-2. Results We observed that there were age-related decreases in the number of acinar cells, increase in eosinophilic zymogen granules in cells, collagen accumulation in fibrotic areas and dilatation in interlobular ducts. Also, while type I collagen and MMP-2 immunoreactivity were moderate in the salivary glands of the young mice, they were high in the salivary glands of the old mice (p=0.001). In the H-score assessment, MMP-2 immunoreactivity was lower at a significant level in young mice than in old mice (p=0.001). Conclusions This study showed that anatomical, physiological and morphological abnormalities occur in all three major salivary glands as a natural consequence of aging.