Correlations Between Single-Photon Emission Computed Tomography Parameters of Salivary Glands and Dry Eye Tests in Patients With Sjögren's Syndrome

ObjectiveTo evaluate the correlations between Single-Photon Emission Computed Tomography (SPECT) parameters of salivary glands and dry eye parameters in patients with Sjögren's syndrome (SS).MethodsA total of 28 patients with SS participated in this prospective study. Dry eye assessments include tear film break-up time (TBUT), corneal fluorescein staining scoring (CFS), Schirmer's I test (SIT) examination and SPECT of salivary gland. The following quantitative parameters were derived from SPECT imaging for salivary glands: Uptake index (UI), the time needed to achieve the minimum counts after Vit C stimulation (Ts), and excretion fraction (EF). The relation between the aforementioned parameters and TBUT, CFS and SIT were analyzed with SPSS 22.0 software.ResultsAll the 28 eyes of the 28 subjects were examined. The mean SIT was 6.04 ± 4.64 mm/5 min (0–18 mm/5 min); the mean CFS was 3.07 ± 2.65 (0–10) and the mean BUT was 2.11 ± 1.97 s (0–9 s). The mean EF value was 0.52 ± 0.12 (0.26–0.75) in parotid glands and 0.45 ± 0.10 (0.30–0.67) in submandibular glands, respectively. The mean UI value was 9.33 ± 1.68 (6.03–13.20) in parotid glands and 9.92 ± 1.48 (7.08–12.60) in submandibular glands, respectively. The mean Ts (min) was 5.32 ± 3.01 (2.00–12.00) in parotid glands and 11.09 ± 7.40 (2.00- 29.00 min) in submandibular glands, respectively. It was found that EF positively correlates with SIT in patients with SS (r = 0.499 and 0.426 in parotid glands and submandibular glands, with P < 0.05), while no significant correlation was found between the UI, Ts and CFS, TBUT (P > 0.05).ConclusionsThe EF was positively correlated with SIT in patients with SS, it could reflex the dysfunction of salivary glands in SS patients. So, EF may be a valuable parameter for the diagnosis of SS patients with lacrimal gland secretion dysfunction.

Salivary gland ultrasonography in primary Sjögren’s syndrome from diagnosis to clinical stratification: a multicentre study

Background To determine the diagnostic accuracy of major salivary gland ultrasonography (SGUS) in primary Sjögren’s syndrome (pSS) using the novel Outcome Measures in Rheumatology Clinical Trials (OMERACT) scoring system in a large-scale multicentre study. Methods SGUS was conducted for 246 pSS patients, 140 control subjects with conditions other than SS and 27 healthy control subjects. The echostructure features from the parotid and submandibular glands on both sides were graded using the novel OMERACT scoring system. Receiver operating characteristic curves were used to describe the diagnostic accuracy of the scoring system for pSS. The associations between the SGUS and disease characteristics were analysed to evaluate the clinical value of SGUS for pSS. Results The US scores in the pSS group were significantly higher than those in the non-pSS group (p < 0.001). The level of diagnostic accuracy was comparable with the scores of all four glands (AUC=0.908) when only the parotid and submandibular glands on either side were scored (AUC=0.910, 0.904, respectively). The optimal cut-off value for the left (right) parotid gland and the left (right) submandibular gland was 4, with maximal sensitivity (75.6% and 77.2%, respectively) and specificity (91.6% and 92.2%, respectively). The pSS patients with positive SGUS results presented a longer disease duration, parotid enlargement, dental loss and higher levels of serological markers, such as anti-SSA, anti-SSB, positive RF, IgG and γ-globulin%. Conclusions SGUS with the OMERACT scoring system yields high sensitivity and specificity, demonstrating high diagnostic feasibility for pSS. The SGUS may have implications for deciding disease severity and treatment efficacy.

Quantitative assessment of dry mouth in scrub typhus using salivary scintigraphy

Scrub typhus is an acute febrile illness caused by the intracellular pathogen Orientia tsutsugamushi. The clinical features include fever, myalgia, lymphadenopathy, and dry mouth. However, no studies have assessed the symptom of dry mouth in patients with scrub typhus. We investigated the pattern of salivary scintigraphy during the acute febrile state and compared it with any changes after treatment. Fourteen patients underwent both pre- and post-treatment salivary scintigraphy. Imaging analysis was conducted using radioactivity in the oral cavity, parotid glands, and submandibular glands. During the acute phase, the radioactivity in the oral cavity markedly decreased, while that in the parotid and submandibular glands was preserved. After treatment, radioactivity in the oral cavity showed a significant increase at 20-min, 40-min, and after wash-out. The ejection fraction (%) of the parotid glands also increased after treatment. In contrast, the radioactivity levels of the parotid and submandibular glands were not statistically different after treatment. Salivary scintigraphy indicated that insufficient saliva excretion from the salivary glands into the oral cavity was one reason for the dry mouth reported by patients with scrub typhus. In the future, salivary scintigraphy imaging could contribute to the evaluation of dry mouth in patients with scrub typhus.

Performance Evaluation of Multiple Ultrasonographical Methods for the Detection of Primary Sjögren’s Syndrome

Major salivary gland ultrasonography (SGUS) is increasingly being recognized as having critical roles in differentiating primary Sjögren’s syndrome (pSS) from other connective tissue disorders. Contrast-enhanced ultrasonography (CEUS) has been reported to evaluate microvascularity of lesions in different tissues with objective angiographic index, eliminating the observer-dependent defect of ultrasonography. However, there are few relevant studies concentrating on the application of CEUS in the diagnosis and assessment for pSS, and their clinical utility prospect remains uncertain. In this study, a total of 227 eligible patients were enrolled, including 161 pSS and 66 non-pSS patients with comprehensive ultrasonographic evaluation of the parotid and submandibular glands, including grayscale ultrasonography, color Doppler sonography (CDS), and CEUS. Compared with non-pSS, pSS patients had significantly higher grayscale ultrasound (US) scores and CDS blood grades in the parotid gland and significantly higher grayscale US and CEUS scores in the submandibular glands. Diagnostic model combining ultrasonographic signatures, anti-SSA/Ro60, and keratoconjunctivitis sicca (KCS) tests showed a remarkable discrimination [mean area under the curve (AUC)0.963 in submandibular glands and 0.934 in parotid glands] for pSS, and the nomogram provided excellent prediction accuracy and good calibration in individualized prediction of pSS. A combination of multiple ultrasonographical examinations of the major salivary glands (SGs) is a promising technique that may be used as a practical alternative to minor SG biopsy in the detection of pSS.

Salivary Lactoferrin Expression in a Mouse Model of Alzheimer’s Disease

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.

Effects of Fluoride on Submandibular Glands of Mice: Changes in Oxidative Biochemistry, Proteomic Profile, and Genotoxicity

Although fluoride (F) is well-known to prevent dental caries, changes in cell processes in different tissues have been associated with its excessive exposure. Thus, this study aimed to evaluate the effects of F exposure on biochemical, proteomic, and genotoxic parameters of submandibular glands. Twenty one old rats (n = 30) were allocated into three groups: 60 days administration of drinking water containing 10 mgF/L, 50 mgF/L, or only deionized water (control). The submandibular glands were collected for oxidative biochemistry, protein expression profile, and genotoxic potential analyses. The results showed that both F concentrations increased the levels of thiobarbituric acid–reactive substances (TBARS) and reduced glutathione (GSH) and changed the proteomic profile, mainly regarding the cytoskeleton and cellular activity. Only the exposure to 50 mgF/L induced significant changes in DNA integrity. These findings reinforce the importance of continuous monitoring of F concentration in drinking water and the need for strategies to minimize F intake from other sources to obtain maximum preventive/therapeutic effects and avoid potential adverse effects.

Renal and Salivary Gland Functions after Three Cycles of PSMA-617 Therapy Every Four Weeks in Patients with Metastatic Castration-Resistant Prostate Cancer

Background: [177Lu]Lu-PSMA-617 radioligand therapy (PSMA-RLT) could affect kidney and salivary gland functions in metastatic castration-resistant prostate cancer (mCRPC) patients. Methods: We retrospectively analyzed clinical, renal, and salivary scintigraphy data and salivary [68Ga]Ga-PSMA-11 ligand PET scan measures such as metabolic volume and SUVmax values of 27 mCRPC men (mean age 71 ± 7 years) before and 4 weeks after receiving three cycles of PSMA-RLT every 4 weeks. Twenty-two patients additionally obtained renal and salivary scintigraphy prior to each cycle. A one-way ANOVA, post-hoc Scheffé test and Cochran’s Q test were applied to assess organ toxicity. Results: In total, 54 PSMA PET scans, 98 kidney, and 98 salivary scintigraphy results were evaluated. There were no significant differences for the ejection fraction, peak time, and residual activity after 5 min for both parotid and submandibular glands prior to each cycle and 4 weeks after the last cycle. Similarly, no significant differences in serum creatinine and renal scintigraphy parameters were observed prior to each cycle and 4 weeks after the last treatment. Despite there being no changes in the metabolic volume of both submandibular glands, SUVmax values dropped significantly (p < 0.05). Conclusion: Results evidenced no alterations in renal function and only minimal impairment of salivary function of mCRPC patients who acquired an intense PSMA-RLT regimen every 4 weeks.

Effects of tobacco smoke inhalation on the morphology and cell proliferation rate in Wistar rats submandibular glands

Cigarette smoke compromises the salivary glands, altering saliva. Cotinine is the most effective biomarker to assess tobacco consumption, and passive smokers are characterized by serum cotinine levels above 2.1 ng/mL. This study aimed to evaluate the effect of exposure to cigarette smoke on rats submandibular glands. The morphology, the proliferative cells of intercalated ducts (immunohistochemistry for KI-67) and its correlation with serum cotinine levels were analyzed. Wistar rats were grouped: control (C); inhalation of smoke for 30 days (T1) and 60 days (T2). Data were analyzed with the Levene variance homogeneity test, Spearman's test, ANOVA and Tukey's post-test, with significance p<0.05. Morphology showed a preserved parenchyma in C, and altered secretory cells in T1 and T2. There was a significant reduction in the number of proliferative cells [ANOVA, F = 4.726; d.f. = 2, 26; p<0.05]: C vsT1 (p<0.05) and C vs T2 (p<0.05). T1 and T2 serum cotinine levels were significantly higher (p<0.05) than C. There was a significant negative correlation [ρ = -0.418, n=27, p<0.05] between serum cotinine levels and the rate of cellular proliferation. These results suggest that of tobacco smoke inhalation has a decreased of the cellular proliferation rate and altered morphology in submandibular glands de ratos Wistar.

Salivary Gland Ultrasonography In Primary Sjögren's Syndrome From Diagnosis To Clinical Stratification: A Multicentre Study

Background: To determine the diagnostic accuracy of major salivary gland ultrasonography (SGUS) in primary Sjögren’s syndrome (pSS) using the novel Outcome Measures in Rheumatology Clinical Trials (OMERACT) scoring system in a large-scale multicentre study.Methods: SGUS was conducted for 246 pSS patients, 140 control subjects with conditions other than SS and 27 healthy control subjects. The echostructure features from the parotid and submandibular glands on both sides were graded using the novel OMERACT scoring system. Receiver operating characteristic curves were used to describe the diagnostic accuracy of the scoring system for pSS. The associations between the SGUS and disease characteristics were analysed to evaluate the clinical value of SGUS for pSS.Results: The US scores in the pSS group were significantly higher than those in the non-pSS group (P < 0.001). The level of diagnostic accuracy was comparable with the scores of all four glands (AUC=0.908) when only the parotid and submandibular glands on either side were scored (AUC=0.910, 0.904, respectively). The optimal cut-off value for the parotid and submandibular glands was 4, with maximal sensitivity (75.6% and 77.2%, respectively) and specificity (91.6% and 92.2%, respectively). The pSS patients with positive SGUS results presented a longer disease duration, parotid enlargement, dental loss and higher levels of serological markers, such as anti-SSA, anti-SSB, positive RF, IgG and γ-globulin%. Conclusions: SGUS with the OMERACT scoring system yields high sensitivity and specificity, demonstrating high diagnostic feasibility for pSS. The SGUS may have implications for deciding disease severity and treatment efficacy.