Salivary gland 99mTc-scintigraphy: a grading scale and correlation with major salivary gland flow rates

Sequential salivary gland scintigraphy with 99mTc-technetium pertechnetate (Tc-99) is a safe, minimally invasive test for study of major salivary glands. However, its relationship to salivary function has not been investigated in detail. We have investigated the relationship between major salivary gland flow rates and Tc-99 scans and developed a new rating scale using scans of a control group with normal salivary function. Salivary flow rates and Tc-99 scans were obtained from healthy, non-medicated subjects (n = 33) and from xerostomic patients (n = 22). There were significant differences between the groups for salivary flow rates and Tc-99 ratings. Significant correlations were found between salivary flow rates and Tc-99 ratings in the control and xerostomic groups. The Tc-99 rating scale proved reliable in assessing salivary dysfunction, and showed a high inter-examiner correlation. These results demonstrate the usefulness of salivary gland scintigraphy in assessing major salivary gland flow rates and the utility of a new rating scale.     

Dynamic changes in bone metabolism in the rat temporomandibular joint after molar extraction using bone scintigraphy

Functional adaptation with reformation of bone tissue structure occurs after changes in mechanical stress distribution. To examine how occlusal changes affect the dynamics of bone metabolism in the mandibular condyle, bone scintigraphy of rat condyles was taken using ^99mtechnetium-methylene-diphosphonate (^99mTc-MDP) after extraction of maxillary molars resulting in unilateral loss of occlusal support. Accumulation of ^99mTc-MDP was significantly higher in the condyles on the extracted side than on the intact side 3 d after molar extraction. In addition, bone mineral density (BMD) and osteoprotegerin expression in extracted-side condyles were significantly increased while osteoclast numbers were significantly decreased when compared with intact-side condyles. These differences were not detected 28 d after molar extraction. These findings suggest that occlusal change transiently results in changes in the dynamics of bone metabolism at the mandibular condyles through the downregulation of osteoclastogenesis. These changes may be involved in functional adaptation of the temporomandibular joint.     

The salivary gland component of Sj?gren's syndrome: an evaluation of diagnostic methods

The diagnostic value of sialography, scintigraphy, sialometry, and labial salivary gland biopsy--as indicators of salivary gland dysfunction in Sj?gren's syndrome (SS)--was evaluated in 41 patients suspected of having SS. In about 70% of the cases, each of the four examinations showed changes that could indicate a salivary gland component of SS. However, the disease specificity of sialographic and scintigraphic examinations was low. Although the specificity of the labial salivary gland biopsy examination is considered high, our study revealed some cases in which a focus score of 1 to 3 was not accompanied by abnormal changes in either sialometry, sialography, or scintigraphy. At a focus score of more than 3, a fair amount of agreement on the results of the various diagnostic procedures was found. Because labial salivary gland examination shows only minor salivary glands and sialography and scintigraphy include only major salivary glands, variance between different diagnostic procedures is expected. This indicates a potential diagnostic role for sialographic and scintigraphic examination when the labial salivary gland biopsy is insufficient.     

Acute salivary gland hypofunction in the duct ligation model in the absence of inflammation

Objective:  The commonly associated aetiology of salivary gland inflammation and salivary hypofunction has led to the widely held belief that inflammation causes salivary gland hypofunction. Indeed, our own recent study seemed to support this contention. Here, we tested the hypothesis that, in an acute duct ligation model, eliminating inflammation the submandibular gland would recover normal function.
Materials and methods:  Ligation of the rat submandibular gland excretory duct for 24 h was used to induce inflammation and salivary gland hypofunction. A group of duct ligated rats was compared with a second group given dexamethasone, on the day of duct ligation. Twenty-four hours later salivary gland function was assessed and salivary glands were collected.
Results:  Histology and myeloperoxidase activity assay revealed a profound decrease in inflammatory cell infiltration of ligated glands from rats given dexamethasone, compared with ligated glands in the absence of dexamethasone. Salivary flow rate evoked by methacholine was decreased ( P  < 0.01) by approximately 56% (ligated vs control, 79 ± 9  μ l min⁻¹ g⁻¹ vs 177 ± 11  μ l min⁻¹ g⁻¹) and salivary flow from ligated dexamethasone-treated and ligated glands was similar.
Conclusion:  Despite eliminating the inflammatory reaction in the ligated gland, salivary hypofunction was not reversed, suggesting that other mechanisms must be at work in the ligation-induced salivary hypofunction.     

The superficial mandibular gland of the rabbit: a new experimental model for scintigraphic evaluation of salivary glands

The aim of this study was to provide an appropriate experimental model to study functional changes in salivary glands using scintigraphy. Although the rabbit was frequently used for laboratory experiments, there are only a few studies that describe the exact position of its different salivary glands on the sialoscintigram. Twenty rabbits were used for the study; ten of them were anatomically dissected to provide the required topographic anatomy on the different salivary and lacrimal glands. The remaining ten animals underwent a static scintigraphy after extirpation of a particular salivary gland. Changes in the pattern of tracer uptake indicated the exact position of every gland allowing its evaluation. The results show that the 99mTcO4- uptake can only be selectively evaluated in two salivary glands, the superficial mandibular gland and the parotid gland. The superficial mandibular gland was proved to be a particularly useful model to evaluate functional changes of salivary gland parenchyma due to its well defined and high enhanced structure which allows a precise detection and measurement of the tracer uptake. Additionally, the good surgical accessibility of this gland and the existence of a well defined capsule facilitate associated histological studies of its parenchyma.     

Sjögren''s syndrome: the diagnostic potential of early oral manifestations preceding hyposalivation/xerostomia

Sjögren's syndrome (SS) is a systemic autoimmune exocrinopathy that affects mainly the salivary and lacrimal glands, leading to progressive reduction in saliva and tear flow. Although the underlying immuno‐mediated glandular destruction is thought to develop slowly over several years, a long delay from the start of the symptoms to final diagnosis has been frequently reported. A limited knowledge concerning SS natural history is among the major causes of the actual diagnostic delay. Although very few studies have been focused on the analysis of SS early clinical onset, a series of oral features preceding xerostomia/hyposalivation development in patients eventually diagnosed as having SS have been reported. Sialochemistry alterations, salivary gland swelling, early dental loss and sialorrhea have been observed before the onset of typical signs and symptoms (namely xerostomia and/or hyposalivation), which usually lead to SS clinical presentation and diagnosis. Here we suggest, after evaluating available data, that the traditional ‘untouchable’ association between SS and xerostomia/hyposalivation might probably be reconsidered, and that astute clinicians should not underestimate the possible presence or development of SS in patients without xerostomia/hyposalivation and presenting these atypical early oral features.     

Follicular dendritic cells confirm lymphoid organization in the minor salivary glands of primary Sjögren’s syndrome

Background: Sjögren’s syndrome (SS) is an autoimmune chronic inflammatory disorder affecting the salivary and lacrimal glands. The aim of this study was to explore immunophenotypic features of chronic inflammatory reactions in the minor salivary glands in patients with primary SS (pSS). Methods: Formalin‐fixed, paraffin‐embedded labial minor salivary gland tissue sections from randomly selected patients with pSS (n = 60) were investigated for the expression of CD21, CD23, CD35 and IgD by immunohistochemistry. Results: Based on the distribution and staining pattern of CD21, CD23, CD35 and IgD in lymphoid aggregates, several stages of chronic inflammatory reactions were observed. In 12/60 (20%) patients, lymphoid infiltrates with germinal centre (GC)‐like features such as extensive networks of CD21‐, CD23‐ and CD35‐positive cells were observed in the minor salivary gland tissue. Smaller networks and /or focal infiltrates with scattered CD21⁺, CD23⁺ and CD35⁺ cells were observed in the remaining 48/60 (80 %) cases. When dividing patients according to the presence (GC+) or the absence (GC?) of GC in the minor salivary glands, the mean focus score was significantly higher in the GC+ patients (P < 0.05). Double staining of the minor salivary glands revealed focal infiltrates with follicular dentritic cell networks and B cells resembling normal GCs in tonsillar tissue. Conclusion: A particular cellular profile was demonstrated in a sub‐group of patients with pSS and could be linked to serological aberrations. These findings warrant further prospective studies.     

Sjögren's syndrome: clinical and therapeutic features. A review of the literature

Sj?gren' Syndrome (SS), also named Sicca Syndrome, is a complex disease, characterized by a series of clinical symptoms and signs chiefly represented by xerostomia, xerophthalmia and connectival diseases. The pathogenetic mechanisms consist of an autoimmune process leading to salivary and lacrimal glands progressive destruction. There is a primary form with salivary and lacrimal glands compromission only and a second form in which xerostomia and/or xerophthalmia are associated with connectival diseases like rheumatoid arthritis, systemic lupus erythematosus and scleroderma. The diagnosis of SS is rather difficult and it is based on various world-wide established and accepted criteria: the labial minor salivary glands biopsy and the research of specific seric autoantibodies are the basic elements. From the therapeutic point of view, various types of immunomodulant treatments based on cyclosporine, corticosteroids, methotrexate or alpha-interferon have been proposed with different RESULTS: Cholinergic drugs, like pilocarpine and cevimeline, are also used in order to stimulate the gland functionality.     

Activation of innate immune responses through Toll-like receptor 3 causes a rapid loss of salivary gland function

Background:  Recent studies have demonstrated the expression of Toll-like receptor 3 (TLR3) in salivary glands and epithelial cell lines derived from Sjögren's syndrome (SS) patients. As viral infections are considered to be a trigger for SS, in this study we investigated whether in vivo engagement of TLR3 affects salivary gland function.
Methods:  Female New Zealand Black/WF1 mice were repeatedly injected with polyinosinic:polycytidylic acid [poly(I:C)]. TLR3 expression within submandibular glands was studied using immunohistochemistry. RNA levels of inflammatory cytokines in the submandibular glands were determined by real time polymerase chain reaction. Pilocarpine induced saliva volume was used as an index of glandular function.
Results:  Immunohistochemical analysis of submandibular glands showed TLR3 expression in epithelium of serous and mucous acini, granular convoluted tubules, and ducts. Poly(I:C) treatment rapidly up-regulated the mRNA levels of type I interferon (IFN) and inflammatory cytokines in the submandibular glands. One week after treatment, the saliva volumes in poly(I:C) treated mice were significantly reduced in comparison with the phosphate-buffered saline (PBS) treated mice. Hematoxylin and eosin staining showed that salivary gland histology was normal and lymphocytic foci were not detected. Glandular function recovered after poly(I:C) treatment was stopped.
Conclusions:  Our results demonstrate that engagement of TLR3 within the salivary glands results in a rapid loss of glandular function. This phenomenon is associated with the production of type I IFN and inflammatory cytokines in the salivary glands. Restoration of glandular function suggests that for viral etiology of SS, a chronic infection of salivary glands might be necessary.     

舍格伦综合征患者唇腺组织中骨桥蛋白的表达

目的：研究原发性舍格伦综合征（Primary SS）和继发性舍格伦综合征（Secondary SS）患者唇腺组织中骨桥蛋白（OPN）的表达。方法：经病理学检查确诊的SS患者40例,其中原发性SS患者15例,继发性SS患者25例,应用免疫组织化学方法检测患者唇腺组织中的OPN表达量,20例健康志愿者作为正常对照。结果：舍格伦综合征（SS）患者唇腺组织中OPN表达较正常健康人增强。SS患者唇腺组织中,OPN染色阳性率为65.38%,其中,原发性SS阳性率为73.3%,继发性SS阳性率为60.0%,与正常对照的10%比较,差异均有统计学意义（P〈0.05）,但SS二类型之间比较无统计学意义（P〉0.05）。结论：OPN表达在SS患者唇腺组织中均明显增加,提示OPN可能参与了SS疾病的发生和发展过程。     

舍格伦综合征的病因和治疗进展

舍格伦综合征又称干燥综合征,是一种系统性自身免疫性疾病,主要累及唾液腺、泪腺等外分泌腺,局部组织出现淋巴细胞浸润,影响腺体的正常功能。临床上除因唾液腺和泪腺受损,而出现口干、眼干外,可同时伴有全身多系统损害症状。患者血清中存在多种自身抗体和高免疫球蛋白。该疾病在病因、发病机制方面尚未完全明确,诊断标准和治疗等仍有待进一步研究。     

Laser as a therapy for dry mouth symptoms in a patient with Sjögren's syndrome: a case report

This clinical case study reports on dry mouth symptoms in a patient with Sjögren's syndrome (SS) who was treated with laser phototherapy (LPT). A 60-year-old woman diagnosed with SS was referred to the laboratory for lasers in dentistry to treat her severe xerostomia. A diode laser (780 nm, 3.8 J/cm², 15 mW) was used to irradiate the parotid, submandibular, and sublingual glands, three times per week, for a period of 8 months. The salivary flow rate and xerostomia symptoms were measured before, during, and after LPT. Dry mouth symptoms improved during LPT. After LPT, the parotid salivary gland pain and swelling were no longer present. Treatment with LPT was an effective method to improve the quality of life of this patient with SS.     

Loss of PKCδ results in characteristics of Sjögren's syndrome including salivary gland dysfunction

Oral Diseases (2011) 17 , 601–609 Objectives: Chronic infiltration of lymphocytes into the salivary and lacrimal glands of patients with Sjögren’s Syndrome (SS) leads to destruction of acinar cells and loss of exocrine function. Protein kinase C‐delta (PKCδ) is known to play a critical role in B‐cell maintenance. Mice in which the PKCδ gene has been disrupted have a loss of B‐cell tolerance, multiple organ lymphocytic infiltration, and altered apoptosis. To determine whether PKCδ contributes to the pathogenesis of SS, we quantified changes in indicators of SS in PKCδ?/? mice as a function of age. Salivary gland histology, function, the presence of autoantibodies, and cytokine expression were examined. Materials and methods: Submandibular glands were examined for the presence of lymphocytic infiltrates, and the type of infiltrating lymphocyte and cytokine deposition was evaluated by immunohistochemistry. Serum samples were tested by autoantibody screening, which was graded by its staining pattern and intensity. Salivary gland function was determined by saliva collection at various ages. Results: PKCδ?/? mice have reduced salivary gland function, B220+ B‐cell infiltration, anti‐nuclear antibody production, and elevated IFN‐γ in the salivary glands as compared to PKCδ+//+ littermates. Conclusions: PKCδ?/? mice have exocrine gland tissue damage indicative of a SS–like phenotype.     

Review of genes potentially related to hyposecretion in male non-obese diabetic (NOD) mice,a Sjögren's syndrome model

BackgroundSjögren's syndrome (SS) is known to cause dry eyes and mouth due to inflammation of the lacrimal and salivary glands. However, some reports imply that other factors trigger dry eyes and mouth. We previously investigated various factors using RNA-sequencing analysis of lacrimal glands from male non-obese diabetic (NOD) mice, an SS model. In this review, we described (1) the exocrine features of male and female NOD mice, (2) the up- and down-regulated genes in the lacrimal glands of male NOD mice as revealed by our RNA-sequencing data, and (3) comparisons between these genes and data in the Salivary Gland Gene Expression Atlas.HighlightsMale NOD mice exhibit a steady worsening of lacrimal hyposecretion and dacryoadenitis, whereas females exhibit a complex pathophysiological condition that includes diabetic disease, salivary hyposecretion, and sialadenitis. Ctss, an up-regulated gene, is a potential inducer of lacrimal hyposecretion and is also expressed in salivary glands. Two other up-regulated genes, Ccl5 and Cxcl13, may worsen the inflammation of SS in both the lacrimal and salivary glands. The genes Esp23, Obp1a, and Spc25 were detected as down-regulated, but judging the relationship between these genes and hyposecretion is difficult as only limited information is available. Another down-regulated gene, Arg1, is involved in lacrimal hyposecretion, and it also has the potential to cause salivary hyposecretion in NOD mice.ConclusionIn NOD mice, males may be better than females at evaluating the pathophysiology of SS. Some regulated genes revealed by our RNA-sequencing data might be potential therapeutic targets for SS.     

Clinical and laboratorial profile and histological features on minor salivary glands from patients under investigation for Sj?gren’s syndrome

Diagnosis of Sjögren’s syndrome (SS) is complex and the usefulness of labial minor salivary glands biopsy in this process remains controversial. Objectives: to evaluate the clinical and laboratorial profile and histological features on labial minor salivary glands from patients under investigation of SS. Study Design: clinical charts from 38 patients under suspicion of SS and submitted to labial minor salivary glands biopsies were reviewed. Clinical and laboratorial data were retrieved from the clinical files and the HE-stained histological slides were reviewed under light microscopy. Results: mean age of the patients was 56.5 years and 97% were females; histological analysis showed that 42% of the cases showed ductal dilatation, lymphocytic foci were found in 52.6% and, from this group, 80% of the cases presented a foci/lobules ratio above 0.8. Acinar/ductal ratio was considered diminished in 39.5% of the samples. Thirty six (95%) and 32 (84%) patients, respectively, complained about xerostomia and xerophthalmia. A study of the time interval of the symptoms that led to SS investigation showed a mean of 116 months. Moreover, sixty-six percent of the patients had already been submitted to immunosuppressive therapy prior to the labial minor salivary gland biopsy. Age of the patients, scintigraphic alterations on salivary function, antinuclear factor (ANF), anti-Ro and anti-La did not show statistical significant association with the histological features. Lobules/foci ratio above 0.8 was the only histological parameter statistically associated with Sjögren’s syndrome diagnosis (p<0.0001). Conclusions: in the studied sample, lymphocytic foci on salivary glands were the only histological parameter associated to the diagnosis of SS. Early indication of labial minor salivary gland biopsy to patients under investigation of SS could limit the effects of immunosuppressive therapy on the histological features associated with the evolution of salivary gland involvement in SS. Key words:Sjögren syndrome, minor salivary glands, biopsy, lymphocytic foci.     

Peroxiredoxin I is overexpressed in oncocytic lesions of salivary glands

Background:  Oncocytic lesions, particularly frequent in the salivary glands, are characterized by cells with an atypical accumulation of mitochondria. This accumulation has been recognized as a compensatory mechanism to intrinsic functional defects of these organelles, resulting in energy production impairment and increased generation of reactive oxygen species (ROS), including hydrogen peroxide (H₂O₂). Peroxiredoxin I (Prx I) is a H₂O₂ scavenging protein and the expression of its yeast homolog was reported to be influenced by mitochondrial function.
Methods:  In this study, we evaluated Prx I expression in oncocytic lesions of salivary glands by immunohistochemistry.
Results:  Our results showed that Prx I is overexpressed in oncocytes regardless of the salivary gland lesion where they appear.
Conclusions:  These results suggest that Prx I expression in oncocytes is related to its ability to decompose mitochondrial-derived H₂O₂ and that it could provide to the cells a protective role in an environment that, by continuously producing potential DNA-damaging ROS, predisposes to genome instability and cellular transformation.     

Coexistence of Sjögren''s syndrome and sarcoidosis: a report of five cases

Background: Sjögren's syndrome (SS) and sarcoidosis are diseases that can affect the salivary glands and result in the loss of salivary gland function. Most of the criteria used for the diagnosis of SS exclude sarcoidosis before establishing the diagnosis of SS. However, several reports have suggested the coexistence of both SS and sarcoidosis in the same patient. Objective: The purpose of this study was to present five cases that support a true coexistence of sarcoidosis and SS. Methods: Clinical and laboratory findings of patients with evidence of having both SS and sarcoidosis were reviewed. The diagnosis of SS was based on the European community criteria; the diagnosis of sarcoidosis was based on the presence of serological, radiographic and/or histopathologic findings that are consistent with sarcoidosis. Results: All patients fulfilled the criteria for the diagnosis of both diseases. Conclusion: Our findings appear to support a true coexistence of sarcoidosis with SS. Therefore, it is reasonable to suggest removing the exclusion of sarcoidosis from the diagnostic criteria for SS.     

Demonstration of c-erbB-2 oncogene overexpression in salivary gland neoplasms by in situ hybridization

The level of c-erbB-2 cellular mRNA in 18 salivary gland tumours and in 7 normal salivary glands was determined by in situ hybridization using [³⁵S] labelled RNA probes. Computer assisted quantitation of the autoradiographic signal indicated a significantly higher c- erb B-2 expression in the tumour group (22.64 grains per cell ±3.79; 95% CI) as compared to the non-neoplastic salivary gland tissue (4.11 ±0.90; 95% CI). The c-erbB-2 expression as measured by grain counts per cell for the pleomorphic adenomas (16.29± 1.87; 95% CI), mucoepidermoid carcinomas (31.52 ±0.08; 95% CI) and the acinic cell carcinomas (44.24± 17.11; 95% CI) were significantly greater than the expression for the normal group. The acinic cell carcinomas exhibited the greatest level of expression. As observed at the individual cell level, the autoradiographic signal was distributed uniformly in the neoplastic tissues, regardless of the cell type. This study confirms the hypothesis that the c-erb B-2 oncogene is overexpressed at the mRNA level in salivary gland tumours.     

Scintigraphic evaluation of salivary gland function in thyroid cancer patients after radioiodine remnant ablation

Radioiodine (¹³¹I, RAI) has traditionally been used in thyroid cancer treatment but its benefit should be balanced against possible risks. Among them, salivary gland dysfunction has often been discussed, although the reported data have been inconsistent. The aim of our prospective study was to evaluate salivary gland function in 31 thyroidectomised patients (6 men, 25 women; median age 52 yr) before and 4–6 months after RAI remnant ablation (RRA), using activity of 3.7 GBq ¹³¹I-NaI. Salivary gland uptake and excretion fractions were quantitatively assessed with ^99mTc – pertechnetate salivary gland scintigraphy. Pre- and post-treatment values were compared using Wilcoxon signed rank test. No statistically significant difference in the pre- and post-treatment values was observed in parotid or submandibular glands uptake, or in the parotid or submandibular excretion fractions. The calculated power for minimum relevant difference of 25% with the sample size of 31 ranged between 86% and 96% for the individual variables, making our negative results reasonably reliable. The results suggest that RRA with the most commonly used activity of 3.7 GBq has no important impact on salivary gland function. Therefore, the concerns about putative salivary gland functional deterioration following RRA are probably unjustified.     

下颌下腺非侵袭性恶性多形性腺瘤1例报告

唾液腺非侵袭性恶性多形性腺瘤(Ca-ex-PA)又称发生在多形性腺瘤中的原位癌,是较少见的病理类型,临床表现与良性多形性腺瘤相似,有条件完整切除肿瘤,复发或转移少见,预后良好.本文报告1例下颌下腺非侵袭性多形性腺瘤的临床病理学特征,认为鉴别非侵袭性Ca-ex-PA和侵袭性Ca-ex-PA对判断预后十分重要,并影响治疗方案的选择,WHO对唾液腺多形性腺瘤恶变的分型在肿瘤的生物学行为和预后方面具有实际意义.