Search

Background: Diabetes is accompanied by a high prevalence of hyposalivation, causing severe damage to oral and systemic health. Mitochondrial dynamics play important roles in the pathogenesis of various diabetic complications; however, little is known about their roles in diabetic hyposalivation. Materials and Methods: A diabetic mouse model and a high glucose (HG)‐induced diabetic submandibular gland (SMG) cell model were employed. Results: More mitochondria surrounded by autophagosomes and higher expression of mitophagy‐related proteins were detected in the SMGs of diabetic mice and HG‐treated SMG cells. In diabetic SMGs, dynamin‐related protein 1 (DRP1) was upregulated, whereas mitofusin‐2 was downregulated both in vivo and in vitro. Shortened mitochondria and impaired mitochondrial functions were observed in the HG group. A DRP1‐specific inhibitor, mdivi‐1, suppressed mitochondrial fission and mitophagy, as well as restored mitochondrial functions in the HG condition. Moreover, the interaction of F‐actin and DRP1 was enhanced in the diabetic group. Inhibiting F‐actin with cytochalasin D repaired the injured effects of HG on mitochondrial dynamics and functions. Conversely, the F‐actin‐polymerization‐inducer jasplakinolide aggravated mitochondrial fission and dysfunction. Conclusions: F‐actin contributes to HG‐evoked mitochondrial fission by interacting with DRP1, which induces mitophagy and impairs mitochondrial function in SMG cells, ultimately damaging the SMG. [ABSTRACT FROM AUTHOR]

Head and neck cancer (HNC) is the sixth most diagnosed cancer, and treatment typically consists of surgical removal of the tumor followed by ionizing radiation (IR). While excellent at controlling tumor growth, IR often damages salivary glands due to their proximity to common tumor sites. Radiation damage to salivary glands results in loss of secretory function, causing severe and chronic reductions in salivary flow. This leads to the patient-reported sensation of dry mouth, termed xerostomia, which significantly reduces quality of life for HNC patients and survivors. The mechanisms underlying salivary gland damage remain elusive, and therefore, treatment options are scarce. Available therapies provide temporary symptom relief, but there is no standard of care for permanent restoration of function. There is a significant gap in understanding the chronic mechanistic responses to radiation as well as treatments that can be given in the months to years following cessation of treatment. HNC cases are steadily rising; particularly, the number of young patients diagnosed with nonfatal human papillomavirus + HNC continues to increase. The growing number of HNC diagnoses and improved prognoses results in more people living with xerostomia, which highlights the mounting need for restorative treatments. Mechanisms underlying chronic damage include decreases in acinar differentiation markers, increases in acinar cell proliferation, immune and inflammatory dysregulation, and metabolic changes including increases in amino acids and reductions in glycolysis and oxidative phosphorylation, fibrosis, and dysregulated neuronal responses. Currently, promising treatment options include adenoviral gene transfers and stem cell therapy. Thus, this review describes in depth known mechanisms contributing to chronic damage and discusses therapeutic advances in treating chronically damaged glands. Understanding the chronic response to radiation offers potential in development of new therapeutics to reverse salivary gland damage and improve the quality of life of HNC survivors. [ABSTRACT FROM AUTHOR]

Copyright of Revista ADM is the property of Asociacion Dental Mexicana and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Purpose: To determine the impact of sparing submandibular glands (SMGs) on alleviating xerostomia and the functional dynamics of the irradiated parotid glands (PGs) and sublingual glands (SLGs) by diffusion-weighted imaging. Methods: 97 participants underwent 9 rounds of DWI scans before IC (pre-IC), pre-radiation (pre-RT), the midpoint of radiation (mid-RT), the end of radiation (post-RT), 1, 3, 6, 9, 12 (12m-RT) months following radiation. Apparent diffusion coefficient of SMGs (ADCSMG), PGs (ADCPG), and SLGs (ADCSLG), xerostomia questionnaire scores (XQ), and saliva flow rate measures under unstimulated (uSFR) and stimulated condition (sSFR) were documented. Results: ADCPG, ADCSMG, ADCSLG, and XQ showed a rapid increase with a top at 3m-RT followed by regression, whereas uSFR and sSFR had the reverse trend. The change rate of ADC correlated with the dose to PGs, SMGs, and SLGs, as well as uSFR, sSFR, and XQ scores (p < 0.05 for all, except for uSFR with ADCPG (p = 0.063)). Maingroup for ADCPG, uSFR, and sSFR were significant (p values were 0.028, 0.000, 0.000 respectively); ADCPG in SMG sparing group was lower while uSFR, and sSFR were higher than those in the SMG-unsparing group. Simplegroup for ADCSMG, ADCSLG (all p < 0.05 from mid-RT to 12m-RT), and XQ (all p < 0.001 at mid-, 6m-, 9m-, and 12m-RT) were significant; ADCSMG, ADCSLG, and XQ were lower in the SMG-sparing group. Conclusions: SMG protection has a great impact on the functional retention of PGs and SLGs, resulting in alleviating xerostomia and improving quality of life. Trial registration: The clinical trial was also registered with the Chinese Clinical Study Registry (registered number: ChiCTR1900024328, Date: July 6, 2019; URL: https://www.chictr.org.cn/showproj.aspx?proj=40726) [ABSTRACT FROM AUTHOR]

Abstract Background Carcinoma ex-pleomorphic adenoma (CXPA) can either arise primarily as a de novo or from the malignant transformation of a benign pleomorphic adenoma (PA). CXPA mostly occurs in adults aged 50 to 70 years; hence, the occurrence of CXPA in younger ages is not common. Case presentation We report a 27-year-old female who had a history of submandibulectomy for pleomorphic adenoma, and presented with recurrent left submandibular swelling for 4 months. The mass was rapidly increasing in size and was associated with occasional throbbing pain. Examination showed a multilobulated, firm left submandibular swelling with no overlying skin changes. FNAC was performed twice, by conventional and ultrasound-guided techniques, and both concluded as benign salivary gland tumours. CT scan and MRI revealed a well-demarcated tumour with an area of necrosis within, with no obvious invasion into surrounding soft tissue and no significant lymphadenopathy. Having high suspicion of a malignant transformation, the tumour was resected with a concurrent modified radical neck dissection. The histopathological examination confirmed a carcinoma ex-pleomorphic adenoma with the myoepithelial malignant component. The patient subsequently received adjuvant radiotherapy. This case demonstrated that CXPA, although rare, can occur in young adults. Pre-operative FNAC and radiological imaging may mimic a pleomorphic adenoma. Conclusion The presence of recurrent tumours with rapid growth should alarm the clinician about a possible malignant transformation of a benign parotid tumour.

Ionizing radiation, commonly used for head and neck cancer treatment, typically damages the salivary glands, resulting in hyposalivation. The development of treatments to restore this lost function is crucial for improving the quality of life for patients suffering from this condition. To address this clinical need, we have developed an innovative hydrogel by chemically conjugating laminin-1 peptides (A99 and YIGSR) and growth factors, FGF-7 and FGF-10, to fibrin hydrogels. Our results demonstrate that FGF-7/10 and laminin-1 peptides fortified fibrin hydrogel [enhanced laminin-1 peptides fibrin hydrogel (Ep-FH)] promotes salivary gland regeneration and functionality by improving epithelial tissue organization, establishing a healthy network of blood vessels and nerves, while reducing fibrosis in a head and neck irradiated mouse model. These results indicate that fibrin hydrogel-based implantable scaffolds containing pro-regenerative signals promote sustained secretory function of irradiated salivary glands, offering a potential alternative treatment for hyposalivation in head and neck cancer patients undergoing radiation treatment. These unique findings emphasize the potential of fibrin hydrogel-based implantable scaffolds enriched with pro-regenerative signals in sustaining the secretory function of irradiated salivary glands and offer a promising alternative treatment for addressing hyposalivation in head and neck cancer patients undergoing radiation therapy. Radiation therapies used to treat head and neck cancers often result in damaged salivary gland, leading to severe dryness of the oral cavity. In this study, we engineered FGF-7 and FGF-10 and immobilized them into L 1p -FH. The resulting hydrogel, Ep-FH, restored irradiated salivary gland functionality by enhancing epithelial tissue organization, promoting the development of a healthy network of blood vessels and nerves as well as reduction of fibrosis. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: Oral health problems occur if the dry mouth of individuals is not controlled. However, their diet and quality of life are adversely affected. In this study, we aimed to find out the effects of radioactive iodine used on the submandibular glands and to what extent the function changes in the glands would be. Materials and Methods: Among the patients who applied to the nuclear medicine unit of the training and research hospital in 2022, patients who received high-dose (100 mCI RAI) RAI after total thyroidectomy due to differentiated thyroid cancer and were hospitalized in our clinic were included in our study. Among these patients, the salivary gland scintigraphies of those with dry mouth were removed from the system and the submandibular glands were examined. The obtained data were statistically evaluated in IBM SPSS 21.0 for windows program. Results: In this study, 15 patients who received 100 mCI were identified and the conditions of the submandibular glands were examined by scintigraphy. Dry mouth was observed in all of these patients. The function of the submandibular glands was found to be normal in 9 of 15 patients. In 6 patients, varying degrees of loss of f unction w ere d etected. Mann W hitney U t est a nd C hi-square (χ2) test analysis were used for the intergroup comparison of qualitative variables. Spearman correlation test was used to determine the relationships between the variables. The hypotheses were two-sided and a statistically significant result was accepted if p≤0.05. Conclusions: It was determined that dry mouth developed in patients who received high-dose Radioactive Iodine (RAI) 131 treatment for thyroid ca. In 6 of the patients, loss of function of the submandibular glands was observed. Recommendations were made to the patients regarding the symptoms occurring. [ABSTRACT FROM AUTHOR]

The exact mechanism of botulinum toxin A (BTX-A) on submandibular salivary gland (SMG) regarding its function and histology remains unclear. The goal of this work is to clarify the histological effects of BTX-A (at high doses) in SMG in rabbits after one week. Thirty adult male rabbits were used in this study and they arranged as group 1 includes rabbits which received any treatment and kept for one week duration. Group 2 includes rabbits which received 8 units of BTX-A. Group 3 includes rabbits which received 16 units of BTX-A. Animals were euthanized with ether after one week. Specimens of SMG from all rabbits were taken to perform a routine histological preparation and examination. Sections of rabbits of group 2 and group 3 showed evidence of edema that is surrounding striated ducts, congested blood vessels, and even necrosis of both serous and mucous acini. Some sections exhibited features of degeneration of mucous acini. Hemorrhage was noticed in some sections. Injection of either 8 or 16 units of BTX-A induces several alterations in the submandibular glands’ histology.

Objective. Simplified calculation approaches and geometries are usually adopted for salivary glands (SGs) dosimetry. Our aims were (i) to compare different dosimetry methods to calculate SGs absorbed doses (ADs) following [18F]-PSMA-1007 injection, and (ii) to assess the AD variation across patients and single SG components. Approach. Five patients with prostate cancer underwent sequential positron-emission tomography/computed tomography (PET/CT) acquisitions of the head and neck, 0.5, 2 and 4 h after [18F]-PSMA-1007 injection. Parotid and submandibular glands were segmented on CT to derive SGs volumes and masses, while PET images were used to derive Time-Integrated Activity Coefficients. Average ADs to single SG components or total SG (tSG) were calculated with the following methods: (i) direct Monte Carlo simulation with GATE/GEANT4 considering radioactivity in the entire PET/CT field-of-view (MC) or in the SGs only (MCsgo); (ii) spherical model (SM) of OLINDA/EXM 2.1, adopting either patient-specific or standard ICRP89 organ masses (SMstd); (iii) ellipsoidal model (EM); (iv) MIRD approach with organ S -factors from OLINDA/EXM 2.1 and OpenDose collaboration, with or without contribution from cross irradiation originating outside the SGs. The maximum percent AD difference across SG components (δ max) and across patients (Δmax) were calculated. Main results. Compared to MC, ADs to single SG components were significantly underestimated by all methods (average relative differences ranging between −11.9% and −30.5%). δ max values were never below 25%. The highest δ max (=702%) was obtained with SMstd. Concerning tSG, results within 10% of the MC were obtained only if cross-irradiation from the remainder of the body or from the remainder of the head was accounted for. The Δmax ranged between 58% and 78% across patients. Significance. Simple geometrical models for SG dosimetry considerably underestimated ADs compared to MC, particularly if neglecting cross-irradiation from neighboring regions. Specific masses of single SG components should always be considered given their large intra- and inter-patient variability. [ABSTRACT FROM AUTHOR]

Salivary gland damage remains a problem despite advances in radiotherapy schedules for head and neck cancer. Kaempferol, a natural flavonoid, found in several fruits and vegetables, is a good antioxidant. This study was designed to evaluate the possible protective effects of kaempferol on submandibular glands (SMGs) of rats exposed to fractionated gamma irradiation. Twenty-four male adult Wistar albino rats were included in this study and assigned to three groups (n = 8). Rats in group K received kaempferol orally in five doses at a dose of 10 mg/kg/2 days for 10 days. Meanwhile, rats in group R were subjected to fractionated whole-body gamma irradiation at a dose of 2 Gy/5 days/week for 2 weeks (20 Gy), and the KR group received kaempferol as group K and then was subjected to a fractionated whole-body gamma irradiation as group R. SMG samples were collected on days 1 and 7 after the last radiation session; and processed for histopathological and immunohistochemical investigations. The SMGs of group R showed focal atrophy and degeneration. Acini showed vacuolization and had pyknotic hyperchromatic nuclei. Striated ducts degenerated, shrunken, and were surrounded by empty spaces. The percentage of areas covered by cyclooxygenase-2 (COX-2) significantly increased, whereas the percentage of areas covered by proliferating cell nuclear antigen (PCNA) significantly decreased compared with those in group K. Cotreatment with kaempferol (group KR) partially preserved normal gland architecture where acinar vacuolation and degeneration were almost absent; however, some ducts degenerated. A significant decrease in the percentage of areas covered by COX-2 and a significant increase in the percentage of areas covered by PCNA were observed compared with those in group R. Kaempferol has a possible radioprotective effect on the SMGs of rats exposed to fractionated gamma irradiation. [ABSTRACT FROM AUTHOR]

Introduction: Oral microbial homeostasis is a key factor affecting oral health, and saliva plays a significant role in maintaining oral microbial homeostasis. The submandibular gland (SMG) and sublingual gland (SLG) together produce the most saliva at rest. Organic ingredients, including antimicrobial proteins, are rich and distinctive and depend on the type of acinar cells in the SMG and SLG. However, the functions of the SMG and SLG in maintaining oral microbial homeostasis have been difficult to identify and distinguish, given their unique anatomical structures Methods: In this study, we independently removed either the SMG or SLG from mouse models. SMGs were aseptically removed in three mice in the SMGremoval group, and SLGs were aseptically removed in three mice in the SLGremoval group. Three mice from the sham-operated group were only anesthetized and incised the skin. After one month, we analyzed their oral microbiome through 16S rRNA sequencing. And then, we analyzed each gland using proteomics and single-cell RNA sequencing. Results: Our study revealed that the microbiome balance was significantly disturbed, with decreased bacterial richness, diversity, and uniformity in the groups with the SMG or SLG removed compared with the sham-operated group. We identified eight secreted proteins in the SMG and two in the SLG that could be involved in maintaining oral microbial homeostasis. Finally, we identified multiple types of cells in the SMG and SLG (including serous acinar, mucinous acinar, ductal epithelial, mesenchymal, and immune cells) that express potential microbiota homeostasis regulatory proteins. Our results suggest that both the SMG and SLG play crucial roles in maintaining oral microbial homeostasis via excretion. Furthermore, the contribution of the SMG in maintaining oral microbial homeostasis appears to be superior to that of the SLG. These findings also revealed the possible antimicrobial function of gland secreta. Discussion: Our results suggest that control of oral microbial dysbiosis is necessary when the secretory function of the SMG or SLG is impaired. Our study could be the basis for further research on the prevention of oral diseases caused by microbial dysbiosis. [ABSTRACT FROM AUTHOR]

Objectives/hypothesisCore needle biopsy is an effective diagnostic tool widely used in many oncological diagnostic approaches. It provides an adequate tissue sample for histological evaluation of architecture, which allows tumor grading and classification of malignant and benign tumors. This study aimed to provide an updated meta-analysis and systematic review of core needle biopsy in the salivary glands.Study designA literature search using PubMed, Embase, and the Cochrane Library through December 2016.MethodsData on true positives, true negatives, false positives, and false negatives were extracted from the relevant articles. Methodological quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies 2 tool. We calculated accuracy, sensitivity, and specificity with 95% confidence intervals (CIs) using random-effects models that considered both within- and between-study variations.ResultsOur search included 10 observational studies. For core needle biopsy, the sensitivity and specificity for the diagnosis of salivary glands were 0.94 (95% CI: 0.92-0.96, I2  = 18.7%, χ2 P = .27) and 0.98 (95% CI: 0.97-0.99, I2  = 79.6%, χ2 P = .00), respectively. The area under the summary receiver operating characteristic curve was 0.98 (95% CI: 0.97-0.99). Seven hematomas, one case of temporary facial paralysis caused by local anesthesia, and no tumor seeding were reported from a total of 1,315 procedures.ConclusionsUltrasound core needle biopsy of salivary glands is an excellent diagnostic tool in terms of accuracy, technical performance, and safety profile.Level of evidenceNA. Laryngoscope, 128:118-125, 2018.

Purpose: Nasopharyngeal cancer (NPC) has a higher prevalence of regional nodal metastasis than other head and neck cancers; however, level IB lymph node involvement is rare. We evaluated the safety and feasibility of level IB-sparing radiotherapy (RT) for NPC patients. Materials and Methods: We retrospectively reviewed 236 patients with NPC who underwent definitive intensity-modulated RT with or without chemotherapy between 2004 and 2018. Of them, 212 received IB-sparing RT, and 24 received non-IB-sparing RT. We conducted a propensity score matching analysis to compare treatment outcomes according to IB-sparing status. In addition, dosimetric analysis of the salivary glands was performed to identify the relationship between xerostomia and the IB-sparing RT. Results: The median follow-up duration was 78 months (range, 7 to 194 months). Local, regional, and distant recurrences were observed in 11.9%, 6.8%, and 16.1% of patients, respectively. Of the 16 patients with regional recurrence, 14 underwent IB-sparing RT. The most common site categorization of regional recurrence was level II (75%), followed by retropharyngeal lymph nodes (43.8%); however, there was no recurrence at level IB. In the matched cohorts, IB-sparing RT was not significantly related to treatment outcomes. However, IB-sparing RT patients received a significantly lower mean ipsilateral and contralateral submandibular glands doses (all, p < 0.001) and had a lower incidence of chronic xerostomia compared with non-IB-sparing RT patients (p = 0.006). Conclusion: Our results demonstrated that IB-sparing RT is sufficiently safe and feasible for treating NPC. To reduce the occurrence of xerostomia, IB-sparing RT should be considered without compromising target coverage. [ABSTRACT FROM AUTHOR]

Introduction: Most common toxicity of radiotherapy in head and neck malignancy patients is xerostomia. Xerostomia can be prevented by using salivary gland sparing Intensity Modulated Radiation Therapy (IMRT) technique. Aim: To compare Dose Volume Histogram (DVH) of salivary glands in IMRT and 3-Dimensional Conformal Radiation Therapy (3DCRT) and evaluation of xerostomia, mucositis and dysphagia in both groups. Materials and Methods: The present study was a prospective cohort study in which 30 patients were selected. Patients of head and neck cancer reporting to Department of Radiation Oncology, Vydehi Institute of Medical Sciences and Research Centre, Bangalore, Karnataka, India were included. Duration of study was one year (January 2013 to December 2013). Fifteen patients treated with IMRT and 15 patients with 3DCRT to a dose of 60-70 Gy in 30-35 fractions, with or without concomitant cisplatin. The DVH of salivary glands and incidence of xerostomia, mucositis and dysphagia was compared in both the groups. Patients were assessed during the course of radiotherapy and three months postradiotherapy. Results: Mean dose to contralateral parotid was 19.48 Gy in IMRT when compared to 47.31 Gy in 3DCRT. Mean dose to contralateral submandibular was 44.06 Gy in IMRT when compared to 67.63 Gy in 3DCRT. At three, six and seven weeks there was a difference in number of patients having reduced severity of mucositis in IMRT when compared to 3DCRT. There was no significant difference in dysphagia between both groups at three, six and seven weeks and one month after the treatment. No significant difference in xerostomia between both the groups at seven week and one month after treatment. At three months after treatment the difference in xerostomia was significant between both groups (p

The diagnosis of autoimmune pancreatitis (AIP) and immunoglobulin G4-related sclerosing cholangitis (IgG4-SC) may require a somewhat invasive pathological examination and steroid responsiveness. This retrospective study assessed the complemental diagnosis of AIP and IgG4-SC using submandibular gland (SG) ultrasonography (US) in 69 patients, including 54 patients with AIP, 2 patients with IgG4-SC, and 13 patients with both AIP and IgG4-SC. The data from the physical examination and US of SGs to diagnose AIP (n = 67) and IgG4-SC (n = 15) were analyzed. The steroid therapy efficacy in resolving hypoechoic lesions in SGs was evaluated in 36 cases. The presence of IgG4-related pancreaticobiliary disease with multiple hypoechoic lesions in SGs was reduced from 31 to 11 cases after steroid therapy, suggesting that multiple hypoechoic lesions in SGs are strongly associated with IgG4-positive cell infiltrations. Multiple hypoechoic lesions in SGs were observed in 53 cases, whereas submandibular swelling on palpation was observed in 21 cases of IgG4-related pancreaticobiliary diseases. A complemental diagnosis of IgG4-related pancreaticobiliary diseases without a histological diagnosis and steroid therapy was achieved in 57 and 68 cases without and with multiple hypoechoic lesions in SGs, respectively. In conclusion, multiple hypoechoic lesions in SGs are useful for the complemental diagnosis of IgG4-related pancreaticobiliary diseases. [ABSTRACT FROM AUTHOR]

Introduction: Sjögren's syndrome (SS) is a chronic inflammatory autoimmune disease, which affects the exocrine glands. Its primary symptoms are decreased moisture in the mouth and eyes. Therapies are limited to treatment with steroids, which has unpleasant side effects, so new treatments would be beneficial. One possibility might be stem cells, such as bone marrow mesenchymal stem cells (BMMSCs) or dental pulp-derived stem cells (DPSCs); these have been reported to exert immunomodulatory effects on activated lymphoid cells. This study aimed to evaluate the effects of conditioned media from DPSCs (DPSC-CM) or BMMSCs (BMMSC-CM) on salivary functions in SS. Methods: Cytokine array analysis was performed to assess the types of cytokines present in the media. DPSC-CM or BMMSC-CM was administered in an SS mouse model. Histological analysis of the salivary glands was performed, and gene expression levels of inflammatory and anti-inflammatory cytokines in the submandibular glands (SMGs) were evaluated. Results: DPSC-CM contained more anti-inflammatory factors than BMMSC-CM. The mice that were given DPSC-CM had a lower number of inflammation sites in the SMGs than those in the other experimental groups, and their salivary flow rate increased. The expression levels of interleukin (IL)-10 and transforming growth factor-β1 increased in the DPSC-CM group, while those of Il-4, Il-6, and Il-17a decreased. The mice that received DPSC-CM showed a significantly increased percentage of regulatory T cells and a significantly decreased percentage of type T helper 17 cells compared to other groups. Conclusions: These results indicate that DPSC-CM could be an effective therapy for SS-induced hyposalivation, since it decreases the number of inflammatory cytokines and regulates the local inflammatory microenvironment in the SMGs.

IgG4⁃related sialadenitis (IgG4⁃RS) is a type of autoimmune disease that has been recognized in recent years, and the pathogenesis remains unclear. IgG4⁃RS mainly affects the submandibular gland and parotid gland and is characterized by diffuse painless swelling of the bilateral salivary glands and/or lacrimal glands, usually lasting more than 3 months. Some patients have accompanying hearing loss or hearing impairment, sinusitis, lymphadenopathy and other symptoms; nearly half of patients have different degrees of salivary gland secretion disorders. Most patients have elevated serum IgG4 levels, but they cannot be used as the only marker for diagnosis. Histopathology remains the“gold standard”for diagnosis. Presently, submandibular gland biopsy is often used for diagnosis. Histopathology showed lym⁃ phoplasmacytic infiltration, occlusive phlebitis, striated fibrosis; immunohistochemistry showed IgG4 + /IgG + plasma cells > 40%, and IgG4 + plasma cell/high⁃power field vision > 10. Glucocorticoids are regarded as first⁃line drugs for the treat⁃ ment of this disease. Clinically, glucocorticoids are often combined with immunosuppressive agents such as cyclophos⁃ phamide, but no standard drug regimen exists. Most patients have a significant short⁃term treatment effect, and the long⁃ term prognosis requires further study. Patients with a recurrence tendency should adjust the hormone dose over time. In the future, further research is needed regarding the pathogenesis and treatment of the disease to improve the clinical di⁃ agnosis rate and therapeutic effect.

Introduction: Most common toxicity of radiotherapy in head and neck malignancy patients is xerostomia. Xerostomia can be prevented by using salivary gland sparing Intensity Modulated Radiation Therapy (IMRT) technique. Aim: Comparing Dose Volume Histogram (DVH) of salivary glands in IMRT and 3-Dimensional Conformal Radiation Therapy (3DCRT) and evaluation of xerostomia, mucositis and dysphagia in both groups. Materials and Methods: The present study was a prospective cohort study in which 30 patients were selected. Patients of head and neck cancer reporting to Department of Radiation Oncology, Vydehi Institute of Medical Sciences and Research Centre, Bangalore, Karnataka, India were included. Duration of study was one year (January 2013 to December 2013). Fifteen patients treated with IMRT and 15 patients with 3DCRT to a dose of 60-70 Gy in 30-35 fractions, with or without concomitant cisplatin. DVH of salivary glands and incidence of xerostomia, mucositis and dysphagia was compared in both the groups. Patients were assessed during the course of radiotherapy and three months postradiotherapy. Results: Mean dose to contralateral parotid was 19.48 Gy in IMRT when compared to 47.31 Gy in 3DCRT. Mean dose to contralateral submandibular was 44.06Gy in IMRT when compared to 67.63 Gy in 3DCRT. At three, six and seven weeks there was a difference in number of patients having reduced severity of mucositis in IMRT when compared to 3DCRT. There was no significant difference in dysphagia between both groups at three, six and seven weeks and one month after the treatment. No significant difference in xerostomia between both the groups at seven week and one month after treatment. At three months after treatment the difference in xerostomia was significant between both groups (p<0.05) favouring IMRT. No tumour response benefit was seen with IMRT. Conclusion: Radiation dose received by salivary glands by IMRT was significantly less when compared to 3DCRT, thereby reducing the incidence, severity and duration of xerostomia. IMRT helps in reducing the severity and duration of dysphagia and mucositis in comparison to 3DCRT during radiotherapy of head and neck cancer. [ABSTRACT FROM AUTHOR]

In the last few years, microbial infection and innate immune theories have been proposed as an alternative approach explaining the etiopathogenesis and origin of Alzheimer’s disease (AD). Lactoferrin, one of the main antimicrobial proteins in saliva, is an important modulator of immune response and inflammation, and represents an important defensive element by inducing a broad spectrum of antimicrobial effects against microbial infections. We demonstrated that lactoferrin levels in saliva are decreased in prodromal and dementia stages of AD compared with healthy subjects. That finding seems to be specific to cerebral amyloid-β (Aβ) load as such observation was not observed in healthy elderly controls or those subjects with frontotemporal dementia. In the present study, we analysed salivary lactoferrin levels in a mouse model of AD. We observed robust and early reduction of lactoferrin levels in saliva from 6- and 12-month-old APP/PS1 mice. Because saliva is secreted by salivary glands, we presume that deregulation in salivary glands resulting in reduced salivary lactoferrin levels may occur in AD. To test this hypothesis, we collected submandibular glands from APP/PS1 mice, as well as submandibular gland tissue from AD patients and we analysed the expression levels of key components of the salivary protein signalling pathway. A significant reduction in M3 receptor levels was found along with decreased acetylcholine (Ach) levels in submandibular glands from APP/PS1 mice. Similarly, a reduction in M3 receptor levels was observed in human submandibular glands from AD patients but in that case, the Ach levels were found increased. Our data suggest that the ACh-mediated M3 signalling pathway is impaired in salivary glands in AD, resulting in salivary gland dysfunction and reduced salivary lactoferrin secretion.

In the last few years, microbial infection and innate immune theories have been proposed as an alternative approach explaining the etiopathogenesis and origin of Alzheimer's disease (AD). Lactoferrin, one of the main antimicrobial proteins in saliva, is an important modulator of immune response and inflammation, and represents an important defensive element by inducing a broad spectrum of antimicrobial effects against microbial infections. We demonstrated that lactoferrin levels in saliva are decreased in prodromal and dementia stages of AD compared with healthy subjects. That finding seems to be specific to cerebral amyloid-β (Aβ) load as such observation was not observed in healthy elderly controls or those subjects with frontotemporal dementia. In the present study, we analysed salivary lactoferrin levels in a mouse model of AD. We observed robust and early reduction of lactoferrin levels in saliva from 6- and 12-month-old APP/PS1 mice. Because saliva is secreted by salivary glands, we presume that deregulation in salivary glands resulting in reduced salivary lactoferrin levels may occur in AD. To test this hypothesis, we collected submandibular glands from APP/PS1 mice, as well as submandibular gland tissue from AD patients and we analysed the expression levels of key components of the salivary protein signalling pathway. A significant reduction in M3 receptor levels was found along with decreased acetylcholine (Ach) levels in submandibular glands from APP/PS1 mice. Similarly, a reduction in M3 receptor levels was observed in human submandibular glands from AD patients but in that case, the Ach levels were found increased. Our data suggest that the ACh-mediated M3 signalling pathway is impaired in salivary glands in AD, resulting in salivary gland dysfunction and reduced salivary lactoferrin secretion. [ABSTRACT FROM AUTHOR]

Objectives: Salivary dysfunction, such as reduced salivary flow and an altered salivary composition, is caused by several diseases, medical conditions, and medications. The purpose of the present study was to clarify the relationship between hypertension and morphological changes in the submandibular glands. Materials and methods: An epidemiological study was conducted to elucidate the relationship between hypertension and dry mouth. The effects of hypertension on morphological changes and the intima thickness of arteries in the submandibular glands were histopathologically investigated. Results: Among 1933 subjects in the epidemiological study, 155 (8.0%) had dry mouth. A multivariate analysis revealed that dry mouth correlated with age (p < 0.001), sex (p < 0.001), and hypertension (p < 0.05). No significant differences were observed in the size of the submandibular glands between patients with or without hypertension. The average area of acinar cells was smaller in patients with than in those without hypertension (0.366 ± 0.153 vs. 0.465 ± 0.178, p < 0.05). The arteriosclerotic index was significantly higher in patients with than in those without hypertension (0.304 ± 0.034 vs 0.475 ± 0.053, p < 0.05). Conclusions: Hypertension may contribute to the degeneration of the submandibular glands by decreasing the number of acinar cells and promoting fatty infiltration and stenosis of the arteries. Clinical relevance: There may be a correlation between hypertension and the degeneration of the submandibular glands by decreasing the number of acinar cells and promoting fatty infiltration and stenosis of the arteries. [ABSTRACT FROM AUTHOR]

The mammalian salivary gland develops as a highly branched structure designed to produce and secrete saliva. This review focuses on research conducted on mammalian salivary gland development, particularly on the differentiation of acinar, ductal, and myoepithelial cells. We discuss recent studies that provide conceptual advances in the understanding of the molecular mechanisms of salivary gland development. In addition, we describe the organogenesis of submandibular glands (SMGs), model systems used for the study of SMG development, and the key signaling pathways as well as cellular processes involved in salivary gland development. The findings from the recent studies elucidating the identity of stem/progenitor cells in the SMGs, and the process by which they are directed along a series of cell fate decisions to form functional glands, are also discussed. Advances in genetic tools and tissue engineering strategies will significantly increase our knowledge about the mechanisms by which signaling pathways and cells establish tissue architecture and function during salivary gland development, which may also be conserved in the growth and development of other organ systems. An increased knowledge of organ development mechanisms will have profound implications in the design of therapies for the regrowth or repair of injured tissues. In addition, understanding how the processes of cell survival, expansion, specification, movement, and communication with neighboring cells are regulated under physiological and pathological conditions is critical to the development of future treatments. [ABSTRACT FROM AUTHOR]

PurposeTo investigate dosimetry of submandibular glands on xerostomia after intensity-modulated radiotherapy for nasopharyngeal carcinoma (NPC).MethodsFrom September 2015 to March 2016, 195 NPC patients were investigated. Xerostomia was evaluated at 12 months after treatment via the RTOG/EORTC system. The least absolute shrinkage and selection operator regression model was used to optimize feature selection for grades 2–3 xerostomia. Multivariable logistic regression analysis was applied to build a predicting model incorporating the feature selected in the least absolute shrinkage and selection operator regression model. Discrimination, calibration, and clinical usefulness of the predicting model were assessed using the C-index, calibration plot, and decision curve analysis.ResultsThe V30 of the parotid glands was selected based on the least absolute shrinkage and selection operator regression. The nomogram displayed good discrimination with a C-index of 0.698 (95% confidence interval [CI]: 0.626–0.771) and good calibration (model 1). Addition of the dosimetric parameters including the mean dose to the submandibular glands, V50 of the submandibular glands, and volume of the submandibular glands to the model 1 failed to show incremental prognostic value (model 2). The model 2 showed a C-index of 0.704 (95% CI: 0.632–0.776). Decision curve analysis demonstrated that the model 1 was clinically useful when intervention was decided at the possibility threshold of > 20%. Within this range, net benefit was comparable between the model 1 and model 2.ConclusionPGv30 was a major predictive factor of grades 2–3 xerostomia for NPC. In contrast, the mean dose to the submandibular glands, V50 of the submandibular glands, and volume of the submandibular glands were not independent predictive factors.

Purpose: To investigate dosimetry of submandibular glands on xerostomia after intensity-modulated radiotherapy for nasopharyngeal carcinoma (NPC). Methods: From September 2015 to March 2016, 195 NPC patients were investigated. Xerostomia was evaluated at 12 months after treatment via the RTOG/EORTC system. The least absolute shrinkage and selection operator regression model was used to optimize feature selection for grades 2–3 xerostomia. Multivariable logistic regression analysis was applied to build a predicting model incorporating the feature selected in the least absolute shrinkage and selection operator regression model. Discrimination, calibration, and clinical usefulness of the predicting model were assessed using the C-index, calibration plot, and decision curve analysis. Results: The V30 of the parotid glands was selected based on the least absolute shrinkage and selection operator regression. The nomogram displayed good discrimination with a C-index of 0.698 (95% confidence interval [CI]: 0.626–0.771) and good calibration (model 1). Addition of the dosimetric parameters including the mean dose to the submandibular glands, V50 of the submandibular glands, and volume of the submandibular glands to the model 1 failed to show incremental prognostic value (model 2). The model 2 showed a C-index of 0.704 (95% CI: 0.632–0.776). Decision curve analysis demonstrated that the model 1 was clinically useful when intervention was decided at the possibility threshold of > 20%. Within this range, net benefit was comparable between the model 1 and model 2. Conclusion: PGv30 was a major predictive factor of grades 2–3 xerostomia for NPC. In contrast, the mean dose to the submandibular glands, V50 of the submandibular glands, and volume of the submandibular glands were not independent predictive factors. [ABSTRACT FROM AUTHOR]

Nerve growth factor (NGF) is an essential trophic factor for the growth and survival of neurons in the central and peripheral nervous systems. For many years, mouse NGF (mNGF) has been used to treat various neuronal and non-neuronal disorders. However, the biological activity of human NGF (hNGF) is significantly higher than that of mNGF in human cells. Using the CRISPR/Cas9 system, we constructed the transgenic mice expressing hNGF specifically in their submandibular glands. As demonstrated by fluorescence immunohistochemical staining, these mice produced hNGF successfully, with 0.8 mg produced per gram of submandibular glands. hNGF with 99% purity was successfully extracted by two-step ion-exchange chromatography and one-step size-exclusion chromatography from the submandibular glands of these transgenic mice. Further, the purified hNGF was verified by LC–MS/MS. We analyzed the NH2-terminus of hNGF using both Edman degradation and LC–MS/MS-based methods. Both results showed that the obtained hNGF lost the NH2-terminal octapeptide (SSSHPIFH). Moreover, the produced hNGF demonstrated a strong promotion in the proliferation of TF1 cells. [ABSTRACT FROM AUTHOR]

The leaf-nosed bats (Phyllostomidae) are outliers among chiropterans with respect to the unusually high diversity of dietary strategies within the family. Salivary glands, owing to their functions and high ultrastructural variability among lineages, are proposed to have played an important role during the phyllostomid radiation. To identify genes underlying salivary gland functional diversification, we sequenced submandibular gland transcriptomes from phyllostomid species representative of divergent dietary strategies. From the assembled transcriptomes, we performed an array of selection tests and gene expression analyses to identify signatures of adaptation. Overall, we identified an enrichment of immunity-related gene ontology terms among 53 genes evolving under positive selection. Lineage-specific selection tests revealed several endomembrane system genes under selection in the vampire bat. Many genes that respond to insulin were under selection and differentially expressed genes pointed to modifications of amino acid synthesis pathways in plant-visitors. Results indicate salivary glands have diversified in various ways across a functional diverse clade of mammals in response to niche specializations. [ABSTRACT FROM AUTHOR]

Sialolithiasis is the most common cause of sialadenitis in the submandibular gland, in which the highest incidence of this condition occurs, among the major salivary glands. This could be explained by the anatomy of Wharton's duct, and the chemical composition of the saliva produced by this gland. There are several alternatives and techniques for the treatment of sialolithiasis, including lithotripsy, sialoendoscopy, and conservative removal of the sialoliths or complete removal of the submandibular gland, through the transoral and extraoral routes for access to the gland. To determine the form of treatment, characteristics such as topography, diameter, and location of the sialolith in the duct are observed. The aim of this case series was to show our experience gained in two clinical cases of submandibular gland excision through an extraoral approach, using the submandibular access technique. In addition, we discussed the cause of sialolithiasis in these patients and after follow-up, compared the clinical results we obtained with this technique with those reported in the current literature. The submandibular approach or Risdon access continues to be a safe approach to removing the submandibular gland, as it is a commonly used technique and obtained satisfactory results, as shown in these cases. However, the major disadvantages were the less favorable esthetic results and paralysis of the marginal mandibular branch of the facial nerve. [ABSTRACT FROM AUTHOR]

Abstract Background Retinoblastoma is the most common intraocular malignancy occurring in children. It can metastasize to the regional lymph nodes, central nervous system and distant organs usually the bones and bone marrow and very rarely to the soft tissue. Here, we report a case of unilateral retinoblastoma in a 4-year-old girl accompanied by a large metastasis of the parotid and submandibular glands that developed about 6 months previously and gradually increased in size 5 months after enucleation of the left eye. Case presentation A 4-year-old girl with a history of unilateral retinoblastoma presented with a large, painful and worsening mass (about 20 × 23 cm) of the left side of the neck. Following surgery, the orbital tumour was completely resected, and the large tumour invasion range in the left side of the neck was not resected completely. Histopathological examination revealed retinoblastoma of the orbit and the parotid and submandibular glands. After chemotherapy and additional local radiotherapy on the parotid and submandibular glands, the tumour was inactive and stable. Conclusions Delayed detection and inappropriate management contribute to poor outcomes. Fundus examinations, education regarding the early signs of RB, and optimization of the therapeutic strategy for RB may play important roles in ocular health.

Purpose: We investigated the radioprotective effect of endogenous melatonin release at different times associated with the circadian rhythm on head and neck radiotherapy. Materials and methods: Two groups of animals were subjected daily to 8 Gy single fraction radiotherapy in the head and neck region from 5:00 to 6:00 (the morning group) or from 19:00 to 20:00 (the evening group). Corresponding untreated groups served as controls. Submandibular glands from rats sacrificed on the seventh day after irradiation were assessed biochemically and histopathologically. Melatonin, malondialdehyde and superoxide dismutase levels in blood collected immediately prior to irradiation were measured with rat-specific ELISA kits. Results: In irradiated rats, melatonin, malondialdehyde and superoxide dismutase levels were significantly higher in the evening group than in the morning group. In nonirradiated rats, melatonin and superoxide dismutase levels were significantly higher in the evening group than in the morning group. The areas of seromucous acinar cells were similar between the irradiated and nonirradiated evening groups, but the area was higher in the evening irradiated group than in the morning irradiated group. Conclusion: Consideration of endogenous melatonin secretion associated with the circadian rhythm may offer new therapeutic solutions for the complications of head and neck radiotherapy. [ABSTRACT FROM AUTHOR]

Pilocarpine is an M3 muscarinic agonist that is widely used for the treatment of xerostomia caused by various diseases and medical conditions. Pilocarpine induced the secretion of salivary fluid in perfused submandibular glands of rats. The secretion of salivary fluid observed after removal of pilocarpine was referred to as residual fluid secretion. The volume of fluid and time of the residual secretion depended on the dose of pilocarpine. Such a residual effect of pilocarpine was observed on fluid secretion via the paracellular pathway and oxygen consumption. When a muscarinic antagonist was added to the perfusate immediately after cessation of pilocarpine, residual secretion of salivary fluid did not occur. These observations indicate that the residual secretion of salivary fluid is a characteristics of the interaction of pilocarpine with muscarinic receptors. [ABSTRACT FROM AUTHOR]

Dysfunctional salivary glands (SGs) are a clinical challenge due to the lack of effective treatments. Cell therapy with stem/progenitor cells may improve this situation by providing promising therapeutic solutions. Therefore, exploring abundant cellular sources is important. Three major pairs of SGs are located in different anatomic regions: the parotid glands, the submandibular glands, and the sublingual glands. Although SG stem/progenitor cells can be isolated and cultivated from all major SGs as salispheres, the differences among SG origins remain unclear. In this study, salispheres were successfully isolated from all major SGs. The salispheres demonstrated unique cellular features that originated from their native tissues. The characteristic expression profiles and cellular features of SG stem cells were demonstrated in all salispheres. When they were transplanted into irradiated animals, the salispheres were all capable of improving the saliva secretion that was disrupted by irradiation. Typical histologic structures could be observed in most parts of the treated glands, and the fibrotic environments of irradiated submandibular glands were remodeled by all salispheres regardless of origins. This study characterized the cellular features and in vivo effects of salispheres that were derived from different anatomic origins. The results suggest the possibility of functional redundancy among distinct pairs of major SGs, which is useful for the design of cell therapy to treat dysfunctional glandular organs. [ABSTRACT FROM AUTHOR]

In recent years, the role of sympathetic nervous fibers in chronic inflammation has become increasingly evident. At the onset of inflammation, sympathetic activity is increased in the affected tissue. However, sympathetic fibers are largely absent from chronically inflamed tissue. Apparently, there is a very dynamic relationship between sympathetic innervation and the immune system in areas of inflammation, and hence a rapid and easy method for quantification of nerve fiber density of target organs is of great value to answer potential research questions. Currently, nervous fiber densities are either determined by tedious manual counting, which is not suitable for high throughput approaches, or by expensive automated processes relying on specialized software and high-end microscopy equipment. Usually, tyrosine hydroxylase (TH) is used as the marker for sympathetic fibers. In order to overcome the current quantification bottleneck with a cost-efficient alternative, an automated process was established and compared to the classic manual approach of counting TH-positive sympathetic fibers. Since TH is not exclusively expressed on sympathetic fibers, but also in a number of catecholamine-producing cells, a prerequisite for automated determination of fiber densities is to reliably distinct between cells and fibers. Therefore, an additional staining using peripherin exclusively expressed in nervous fibers as a secondary marker was established. Using this novel approach, we studied the spleens from a syndecan-3 knockout (SDC3KO) mouse line, and demonstrated equal results on SNS fiber density for both manual and automated counts (Manual counts: wildtype: 22.57 +/- 11.72 fibers per mm2; ko: 31.95 +/- 18.85 fibers per mm2; p = 0.05; Automated counts: wildtype: 31.6 +/- 18.98 fibers per mm2; ko: 45.49 +/- 19.65 fibers per mm2; p = 0.02). In conclusion, this new and simple method can be used as a high-throughput approach to reliably and quickly estimate SNS nerve fiber density in target tissues. [ABSTRACT FROM AUTHOR]

Renin-angiotensin system (RAS) systemically or locally collaborates with tissue homeostasis, growth and development, which has been extensively studied for its pharmacological implications. This study was primarily aimed at finding and characterizing local RAS in rat parotid, sublingual and submandibular glands. It was also hypothesized that vasoactive drugs could affect the expression of RAS targets, as well as saliva flow and its composition. Therefore, another objective of this study was to compare the effects of losartan (angiotensin II receptor blocker) and isoproterenol (β-adrenergic receptor agonist). Forty-one Wistar rats were divided into three groups and administered a daily intraperitoneal dose of saline, losartan or isoproterenol solutions for one week. The following RAS targets were studied using qPCR: renin (REN), angiotensinogen (AGT), angiotensin converting enzyme (ACE), ACE-2, elastase-2 (ELA-2), AT1-a and MAS receptors, using RPL-13 as a reference gene. Morphology of glands was analyzed by immunohistochemistry using REN, ACE, ACE-2, AT1, AT2 and MAS antibodies. The volume and total protein content of saliva were measured. Our results revealed that ACE, ACE-2, AT1-a, AT2 and MAS receptors were expressed in all salivary gland samples, but REN and ELA-2 were absent. Losartan decreased mRNA expression of RAS targets in parotid (MAS) and submandibular glands (ACE and both AT receptors), without affecting morphological alterations, and significantly decreased saliva and total protein secretions. Isoproterenol treatment affected gene expression profiles in parotid (ACE, ACE-2, AT1-a, MAS, AGT), and submandibular (ACE, AT2, AGT) glands, thus promoting acinar hypertrophy in serous acini, without significant changes in salivary flow or total protein content. These drugs affected mainly acini, followed by duct systems and myoepithelial cells, whereas blood vessels were not affected. In conclusion, there is a local RAS in major rat salivary glands and losartan, an angiotensin II receptor blocker, affected not only the RAS-target gene expression but also decreased salivary flow and total protein content. [ABSTRACT FROM AUTHOR]

Tartrazine is one of the most widely used food additives. The present investigation was carried out on 40 adult male albino rats. They were divided into four groups of ten animals for each. Group I was considered as a control group. Group II was treated with tartrazine daily in a dose 7.5 mg/kg body weight by oral gavage for 30 days. Group III was received 15 mg/kg body weight of tartrazine for the same period. Group IV was administered tartrazine in a dose 100 mg/kg body weight for the whole duration of the experiment. At the end of experiment, samples from the cerebellum, submandibular salivary glands, and kidneys were fixed in neutral buffered formalin 10% and prepared routinely for paraffin sectioning and staining for histopathological and immunohistochemical investigations of proliferating cell nuclear antigen "PCNA" and glial fibrillar acidic protein "GFAP". Tartrazine-treated groups revealed histopathological degenerative changes in the obtained organs. In group II, the cerebellum showed subcortical edema, congestion of the blood vessels, cytoplasmic vacuolations, and pyknosis of the nuclei in the gray matter neurons. Concerning the submandibular glands, they expressed cytoplasmic vacuolations and pyknosis of the nuclei of the acinar cells, congestion of the interacinar blood capillaries, and degenerative changes in the striated duct. The kidneys appeared with interstitial hemorrhage and dilatation of the glomerular capillaries. The PCT and DCT showed ill-defined cell boundaries. The collecting tubules in the renal medulla appeared with flattened epithelial cells. The severity of these changes increases by increasing the dose of tartrazine in group III and reach to the highest level in group IV. The immunoexpression of the GFAP in the cerebellum of the experimental groups was intense compared to the control group. The immunoreactivity of PCNA in the nuclei of the acinar and ductal cells of the submandibular gland and the cells of the renal cortex and medulla was strong in the tartrazine-treated groups compared to the control group. The current study concluded that the tartrazine had serious effect on the cerebellum, submandibular glands, and kidneys that adversely affect the functions of these organs. [ABSTRACT FROM AUTHOR]

Sialolithiasis is a common disease of the major salivary glands, characterized by the obstruction of a salivary gland or its excretory duct due to the formation of calcareous concretions. Sialoliths usually measure from 1 mm to 15 mm have been reported in the literature. The submandibular gland and its duct appear to be the most susceptible sites for this disease. In this article, we report two unique cases, including a giant bilateral case, measuring 50 mm in length and 5 mm in width on the right side and one, 30 mm in length, and 5 mm in width on the left side; and another case, measuring 83 mm in length. The diagnostic and therapeutic approaches consisted of transocclusal radiography with the conservative transoral surgical technique in both cases. The follow-up showed the normal function of the relevant salivary glands. To the best of our knowledge and belief, similar cases have not been reported in the literature.

Development and maturation of submandibular salivary glands are influenced by intrauterine diabetic environment. Several studies investigated the effects of diabetes on the salivary glands. However, the effects of maternal diabetes on the submandibular glands of the offspring was not properly examined. Therefore, the present study was designed to describe the changes in the development of the submandibular glands of the offspring of diabetic mothers. The submandibular glands of the offspring of Streptozotocin (STZ)-induced diabetic female rats were examined at two and four weeks after birth. Detection of mRNA demonstrated that maternal diabetes affects the level of different indicators. The reduction of expression of epidermal growth factor (EGF); a protein mitogen, cytokeratin 5 (CK5); an epithelial cell progenitor, CK7 and aquaporin 5 (AQP5); differentiation markers and B cell lymphoma 2 (Bcl2); an antiapoptotic marker were found. Increase in Bcl2-associated X protein (Bax); an apoptotic marker was detected. These changes indicate their effects on saliva secretion, glands tumorigenesis, growth of normal oral flora and oral microbes, with decreased protein synthesis and production of xerostomia and dental caries. Loss of normal glandular architecture, significant increase in fibrosis, by the detection of collagen fibers, and stagnation of secretory granules were found with atrophic changes in the acinar cells. Marked defect of polysaccharides in the acinar cells, denoting functional changes, was manifested by significant reduction of the intensity of periodic acid-Schiff (PAS) reaction. The positive immunoreactivity of caspase-3, denoting cellular apoptosis, and minimal reaction of alpha-smooth muscle actin (α SMA) and proliferating cell nuclear antigen (PCNA) were evident in the offspring of diabetic mothers. We conclude that maternal diabetes produces degenerative effects in the structure and function of the submandibular salivary glands of the offspring, reflecting possible influences on their secretory activity affecting oral and digestive health. [ABSTRACT FROM AUTHOR]

We retrospectively evaluated the effectiveness of combined use of salivary gland ultrasonography (US) and the 2016 American College of Rheumatology/European League Against Rheumatic Disease (ACR/EULAR) classification criteria for improving the diagnostic efficiency in patients with Sjögren’s syndrome (SS). A US-based salivary gland disease grading system was developed using a cohort comprising 213 SS or non-SS patients who fulfilled the minimum requirements for classifying SS based on the American-European Consensus Group (AECG) and ACR criteria. Using 62 SS or non-SS patients from the 213 patients and who had also undergone all the 5 examinations needed for the ACR/EULAR classification, we compared the diagnostic accuracy of various combinations of the ACR/EULAR and US classifications for diagnosing SS, using the clinical diagnosis of SS by rheumatologists as the gold standard. The ACR/EULAR criteria discriminated clinical SS patients with 77% and 79% accuracy for those with primary or secondary SS and for those with primary SS, respectively. However, the integrated score system of the ACR/EULAR and US classifications yielded 92% and 93% accuracy for these 2 SS patient groups, respectively, provided that US score of 3 was assigned to patients with US grade ≥2, and then patients with integrated threshold score of ≥5 were diagnosed as SS. Cross-validation also indicated improved accuracy of the integrated ACR/EULAR and US score system (91.9 and 93.0% for primary/secondary and primary SS patients, respectively) over that by the ACR/EULAR criteria alone. (74.2 and 86.0%, respectively). The integrated ACR/EULAR and US scoring system can improve the diagnosis of patients with clinical SS. [ABSTRACT FROM AUTHOR]

To study the cytological pattern of salivary glands swellings on fine needle aspiration cytology (FNAC). Methods: Patients who underwent fine needle aspiration cytology (FNAC) for their salivary gland swellings, were included. Data was analyzed from various angles including site, diagnostic categories, diagnostic entities, age and gender. Results: Parotid gland (74.3%) was the most frequently affected site, followed by submandibular gland (23.6%). The cases were divided into four main reporting groups i.e. unsatisfactory, inconclusive/ lesion of undetermined significance, non neoplastic and neoplastic constituting 0.7%, 3.6%, 22.9% and 72.9% of all the lesions respectively. Non neoplastic lesions included non specific sialadenitis, cystic lesions without any evidence of neoplasia and sialadenosis comprising 43.8%, 37.5% and 18.8% of these lesions respectively. Neoplastic lesions were divided into three categories namely benign, malignant and indeterminate. Benign tumors constituted 79 (56.4%), malignant neoplasms consisted of 8 (5.7%) and indeterminate category contained 15 (10.7%) of all cases. Mean age was 43 years and MF ratio was 1:1.7. Pleomorphic adenoma was the most frequent diagnosis among all cases, in all neoplasms as well as in benign neoplasms. Conclusion: Parotid was the commonest site of involvement. Pleomorphic adenoma and mucoepidermoid carcinoma were the most common lesions in benign and malignant neoplastic categories respectively.

Purpose: Primary Sjögren’s syndrome is a multisystem autoimmune disease characterized by hypofunction of salivary and lacrimal glands and possible multi-organ system manifestations. Over the past 15 years, three sets of diagnostic criteria have been proposed, but none has included salivary gland ultrasonography. However, recent studies support its role in the diagnosis and prognostic evaluation of patients with Sjögren’s syndrome. This study aimed to determine the value of salivary gland ultrasonography in the diagnosis and prognosis of Sjögren’s syndrome by relating ultrasonography severity scores to clinical and laboratory data. Methods: Seventy patients who fulfilled the 2002 American-European Consensus Group diagnostic criteria for primary Sjögren’s syndrome were selected from 84 patients receiving care in specialized outpatient clinics at our institution from November 2013 to May 2016. Their serology, European League Against Rheumatism Sjögren’s syndrome disease activity index (ESSDAI), salivary flow rate, immunoglobulin G, and salivary and serum beta-2 microglobulin levels were measured. Salivary gland ultrasonography was performed by an experienced radiologist, using scores of 1–4 to classify salivary gland impairment. Results: Salivary gland ultrasonography scores of 1 or 2 were associated with an ESSDAI < 5. Ultrasonography scores of 3 or 4 were associated with an ESSDAI ≥5 (p = 0.064), a positive antinuclear antibody test (p = 0.006), positive anti-Ro/SSA antibodies (p = 0.003), positive anti-La/SSB antibodies (p = 0.077), positive rheumatoid factor (p = 0.034), and immunoglobulin G levels > 1600 mg/dL (p = 0.077). Salivary flow rate was lower in patients with scores 3 or 4 (p = 0.001). Conclusion: This study provides further evidence that salivary gland ultrasonography can be used not only for diagnosis but also for prognostic evaluation of primary Sjögren’s syndrome. These findings confirm what has been reported in the literature. However, further analyses involving larger matched samples are required to support this finding and include salivary gland ultrasonography as part of the diagnostic criteria for Sjögren’s syndrome. [ABSTRACT FROM AUTHOR]

Background: To study the cytological pattern of salivary glands swellings on fine needle aspiration cytology (FNAC). Methods: Patients who underwent fine needle aspiration cytology (FNAC) for their salivary gland swellings, were included. Data was analyzed from various angles including site, diagnostic categories, diagnostic entities, age and gender. Results: Parotid gland (74.3%) was the most frequently affected site, followed by submandibular gland (23.6%). The cases were divided into four main reporting groups i.e. unsatisfactory, inconclusive/lesion of undetermined significance, non neoplastic and neoplastic constituting 0.7%, 3.6%, 22.9% and 72.9% of all the lesions respectively. Non neoplastic lesions included non specific sialadenitis, cystic lesions without any evidence of neoplasia and sialadenosis comprising 43.8%, 37.5% and 18.8% of these lesions respectively. Neoplastic lesions were divided into three categories namely benign, malignant and indeterminate. Benign tumors constituted 79 (56.4%), malignant neoplasms consisted of 8 (5.7%) and indeterminate category contained 15 (10.7%) of all cases. Mean age was 43 years and MF ratio was 1:1.7. Pleomorphic adenoma was the most frequent diagnosis among all cases, in all neoplasms as well as in benign neoplasms. Conclusion: Parotid was the commonest site of involvement. Pleomorphic adenoma and mucoepidermoid carcinoma were the most common lesions in benign and malignant neoplastic categories respectively. [ABSTRACT FROM AUTHOR]

We performed endoscopic transoral neurectomy of the submandibular and sublingual glands to treat drooling. We bilaterally operated two adult cases with treatment-resistant drooling. In these patients, conventional treatment had failed. Repeated botilinum toxin type A (BOTOX®, Abdi Ibrahim Pharmaceutical Company, Istanbul, Turkey) injections had been effective but were becoming less so. The patients benefited from surgery in that their saliva scores decreased. No issue emerged over 6 months of follow-up. Endoscopic transoral neurectomy of the submandibular and sublingual glands reduces saliva production and allows management of drooling in treatment-resistant patients. Laryngoscope, 127:1604-1607, 2017. [ABSTRACT FROM AUTHOR]

Salivary glands are a site of human cytomegalovirus (CMV) replication, latency, and persistence. Prolonged secretion of virus in saliva for months following a primary infection contribute to horizontal transmission. In order to better understand the early effects of CMV on salivary glands and the mechanisms of viral persistent replication, submandibular glands of six CMV congenitally infected fetuses at 21 weeks gestation were studied. Three fetuses at the same gestational age from CMV-seronegative women were compared as negative controls. Tissue viral load and the type of inflammatory infiltrate were evaluated. Moreover, development and branching of salivary glands, the number of myoepithelial cells, cellular proliferation, and expression of secretory proteins of the saliva (Gross Cystic Disease Fluid Protein-15 and lysozyme) were studied. A low viral load and rare CMV-positive cells associated with T CD8 cytotoxic lymphocytes were observed. Branching was impaired with a decrease in terminal acinar structures, the number of myoepithelial cells, and cellular proliferation were reduced. In addition, a compromised secretion of defense proteins involved in the oral humoral immunity was observed. These findings suggest that CMV may affect salivary glands, impairing structure development and secretion of defense proteins, probably responsible for the prolonged viral shedding in saliva. J. Med. Virol. 89:318-323, 2017. © 2016 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Radiotherapy (RT) continues to play a key role in the management of head and neck cancer (HNC). Xerostomia remains a principal detriment to the quality of life (QoL) for 80 % of surviving patients receiving head and neck radiation. Radiation-induced injury to the salivary glands is dose-dependent, and thus efforts have been focused on decreasing radiation to the salivary glands. Decreased saliva production reduces both short-term and long-term quality of life in head and neck survivors by impacting on taste and contributing to dysphagia. Several radioprotective agents to the salivary gland have been investigated. Although not widely practiced, surgical transfer of the submandibular gland prior to RT is the mainstay of surgical options in preventing xerostomia. This review focuses on the strategies to improve xerostomia following radiation therapy in head and neck cancers., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The lingual nerve is a terminal branch of the mandibular nerve. It is varied in its course and in its relationship to the mandibular alveolar crest, submandibular duct and also the related muscles in the floor of the mouth. This study aims to understand the course of the lingual nerve from the molar area until its insertion into the tongue muscle. This cadaveric research involved the study of 14 hemi-mandibles and consisted of two parts: (i) obtaining morphometrical measurements of the lingual nerve to three landmarks on the alveolar ridge, and (b) understanding non-metrical or morphological appearance of its terminal branches inserting in the ventral surface of the tongue. The mean distance between the fourteen lingual nerves and the alveolar ridge was 12.36 mm, and they were located 12.03 mm from the lower border of the mandible. These distances were varied when near the first molar (M1), second molar (M2) and third molar (M3). The lingual nerve coursed on the floor of the mouth for approximately 25.43 mm before it deviated toward the tongue anywhere between the mesial of M1 and distal of M2. Thirteen lingual nerves were found to loop around the submandibular duct for an average distance of 6.92 mm (95% CI: 5.24 to 8.60 mm). Their looping occurred anywhere between the M2 and M3. In 76.9% of the cases the loop started around the M3 region and the majority (69.2%) of these looping ended at between the first and second molars and at the lingual developmental groove of the second molar. It gave out as many as 4 branches at its terminal end at the ventral surface of the tongue, with the presence of 2 branches being the most common pattern. An awareness of the variations of the lingual nerve is important to prevent any untoward complications or nerve injury and it is hoped that these findings will be useful for planning of surgical procedures related to the alveolar crest, submandibular gland/ duct and surrounding areas. [ABSTRACT FROM AUTHOR]