Distinctive profile of monomeric and polymeric anti-SSA/Ro52 immunoglobulin A1 isoforms in saliva of patients with primary Sjögren's syndrome and Sicca.

OBJECTIVE: Primary Sjögren's syndrome (pSS) is the second most common chronic autoimmune connective tissue disease. Autoantibodies, immunoglobulin (IgG) anti-SSA/Ro, in serum is a key diagnostic feature of pSS. Since pSS is a disease of the salivary gland, we investigated anti-SSA/Ro52 in saliva. METHODS: Using a novel electrochemical detection platform, Electric Field-Induced Release and Measurement, we measured IgG/M/A, IgG, IgA, IgA isotypes (IgA1 and IgA2) and IgA1 subclasses (polymeric and monomeric IgA1) to anti-SSA/Ro52 in saliva supernatant of 34 pSS, 35 dry eyes and dry mouth (patients with Sicca) and 41 health controls. RESULTS: Saliva IgG/M/A, IgG, IgA, IgA isotypes and IgA1 subclasses to anti-SSA/Ro52 differed significantly between pSS, non-pSS Sicca and healthy subjects. Elevated monomeric IgA1 was observed in patients with non-pSS Sicca while elevated polymeric IgA1 (pIgA1) was observed in patients with pSS. Salivary polymeric but not monomeric IgA1 (mIgA1) isoform correlated with focus score (r2=0.467, p=0.001) CONCLUSIONS: Salivary anti-Ro52 polymeric IgA1 isoform is associated with glandular inflammation in pSS, while salivary monomeric IgA1 is associated with Sicca. Whether IgA1 isotope switching plays a role in the progression of the Sicca to pSS warrants further investigation.

Seronegative patients with primary Sjögren's syndrome and non-pSS sicca test positive for anti-SSA/Ro52 and -Ro60 in saliva.

OBJECTIVES: Testing for anti-SSA/Ro antibodies in serum is essential in the diagnostic work-up for primary Sjögren's syndrome (pSS). In this study, we aimed to validate our previous assay for detection of salivary anti-SSA/Ro52, and to develop assays for detection of salivary anti-SSA/Ro60 and for detection of anti-Ro52 and -Ro60 in plasma using the electric field-induced release and measurement (EFIRM) platform. METHODS: Whole saliva samples from two independent Danish cohorts (DN1 and DN2) including 49 patients with pSS, 73 patients with sicca symptoms, but not fulfilling the classification criteria for pSS (non-pSS sicca), and 51 healthy controls (HC), as well as plasma samples from the DN1 cohort were analyzed using EFIRM to detect anti-SSA/Ro52 and -Ro60. RESULTS: In the DN1 cohort, 100 % in the pSS group and 16 % in the non-pSS sicca group were serum anti-SSA/Ro positive by ELISA. EFIRM detected anti-SSA (Ro52 and/or -Ro60) in plasma and saliva in 100 % and 96 % patients with pSS, and 16 % and 29 % with non-pSS sicca. In the DN2 cohort, 80 % patients with pSS and 26 % with non-pSS sicca were serum anti-SSA/Ro positive. Salivary anti-SSA discriminated patients with pSS from HC and non-pSS sicca with an AUC range of 0.74-0.96 in the DN1 and DN2 cohorts. EFIRM discriminated pSS from non-pSS sicca with an AUC of 0.98 in plasma. CONCLUSION: Our findings suggest that salivary anti-SSA/Ro antibodies are potential discriminatory biomarkers for pSS, which may also identify seronegative patients, addressing the unmet clinical need of early detection and stratification of pSS.

Immunoassay Detects Salivary Anti-SSA/Ro-52 Autoantibodies in Seronegative Patients with Primary Sjögren's Syndrome.

The diagnostic work-up for Sjögren's syndrome is challenging and complex, including testing for serum autoantibodies to SSA/Ro and a labial salivary gland biopsy. Furthermore, the diagnosis is often delayed. In this study, we tested the hypothesis that anti-SSA/Ro autoantibodies are detectable in the saliva of patients with primary Sjögren's syndrome (pSS) because the disease affects the salivary glands, and these autoantibodies display greater discriminatory performance in saliva than in serum. SSA/Ro-52 Ags were used to develop what is, to our knowledge, a novel quantitative electrochemical-based immunoassay: the electric field-induced release and measurement (EFIRM) platform. The clinical utility was determined by measuring salivary anti-SSA/Ro-52 autoantibodies in patients with pSS and sicca (n = 34), patients without pSS with sicca (n = 35), and healthy subjects (n = 41). The statistical analysis of discrimination included the area under the receiver operating characteristic curve. Salivary anti-SSA/Ro-52 autoantibodies were measured in 94% (32 of 34) of patients with pSS with 85% (29 of 34) seropositivity. Four of the five seronegative patients with pSS had EFIRM-measurable anti-SSA/Ro-52 autoantibodies in saliva. Additionally, 60% (21 of 35) of the seronegative patients without pSS who had sicca had EFIRM-detectable SSA/Ro-52 autoantibodies in saliva, indicating the onset of autoimmune disease. Two of the 41 healthy control subjects had EFIRM-detectable SSA/Ro-52 autoantibodies in their saliva. Salivary SSA/Ro-52 autoantibodies significantly discriminated patients with pSS or patients with the initial stage of autoimmune disease from healthy subjects with an area under the receiver operating characteristic curve of 0.91. Our findings suggest that the proposed saliva SSA/Ro-52 immunoassay improves early and accurate diagnosis of seronegative patients with pSS and patients with early-onset autoimmune disease.

Sjögren's syndrome: novel insights from proteomics and miRNA expression analysis.

Introduction: Sjögren's syndrome (SS) is a systemic autoimmune disease, which affects the exocrine glands leading to glandular dysfunction and, particularly, symptoms of oral and ocular dryness. The aetiology of SS remains unclear, and the disease lacks distinctive clinical features. The current diagnostic work-up is complex, invasive and often time-consuming. Thus, there is an emerging need for identifying disease-specific and, ideally, non-invasive immunological and molecular biomarkers that can simplify the diagnostic process, allow stratification of patients, and assist in monitoring the disease course and outcome of therapeutic intervention in SS. Methods: This systematic review addresses the use of proteomics and miRNA-expression profile analyses in this regard. Results and discussion: Out of 272 papers that were identified and 108 reviewed, a total of 42 papers on proteomics and 23 papers on miRNA analyses in saliva, blood and salivary gland tissue were included in this review. Overall, the proteomic and miRNA studies revealed considerable variations with regard to candidate biomarker proteins and miRNAs, most likely due to variation in sample size, processing and analytical methods, but also reflecting the complexity of SS and patient heterogeneity. However, interesting novel knowledge has emerged and further validation is needed to confirm their potential role as biomarkers in SS.

Association of G protein-coupled receptor 78 with salivary dysfunction in male Sjögren's patients.

OBJECTIVE: Sjögren's disease (SjD) has a strong sex bias, suggesting an association with sex hormones. Male SjD represents a distinct subset of the disease, but the pathogenic mechanisms of male SjD is poorly characterized. The aim of this study is to identify initiating events related to the development of gland hypofunction and autoimmunity in male SjD patients. MATERIALS AND METHODS: Human minor salivary glands were transcriptomically analyzed with microarrays to detect differentially expressed genes in male SjD patients. Identified genes were tested on their involvement in the disease using conditional transgenic mice and gene-overexpressing cells. RESULTS: GPR78, an orphan G protein-coupled receptor, was overexpressed in the salivary glands of male SjD patients compared with male healthy controls and female SjD patients. Male GPR78 transgenic mice developed salivary gland hypofunction with increased epithelial apoptosis, which was not seen in control or female transgenic mice. In cell culture, GPR78 overexpression decreased lysosomal integrity, leading to caspase-dependent apoptotic cell death. GPR78-induced cell death in vitro was inhibited by treatment with estradiol. CONCLUSION: GPR78 overexpression can induce apoptosis and salivary gland hypofunction in male mice through lysosomal dysfunction and increased caspase-dependent apoptosis in salivary gland epithelium, which may drive disease in humans.

Impact of medications on salivary flow rate in patients with xerostomia: a retrospective study by the Xeromeds Consortium.

OBJECTIVES: This study evaluates the impact of systemic medications and polypharmacy on unstimulated (UWS) and chewing-stimulated whole saliva (SWS) flow rates in patients with xerostomia. MATERIAL AND METHODS: This cross-sectional multicenter study is based on data of patients referred to five oral medicine outpatient practices in Europe and USA from January 2000 and April 2014. Relevant demographic, social, medical history and current medications were collected. RESULTS: The study included 1144 patients, 972 (85%) females, with a mean (SD) age of 59 (14.1) years. In unmatched patients, the UWS flow rate was lower in patients taking a medication (vs. not taking a medication) from the following drug categories: opioid analgesics, anticonvulsants, antidepressants, antihypertensives, benzodiazepines, corticosteroids, diuretics, disease-modifying antirheumatic drugs (DMARDs) and hormones. There was a greater negative effect on SWS flow rate in patients taking (vs. not taking) anticonvulsants, antidepressants, benzodiazepines, corticosteroids, and DMARDs. In matched patients, both UWS (0.22 vs. 0.19 ml/min; p = 0.03) and SWS (0.97 vs. 0.85 ml/min; p = .017) flow rates were higher in patients on non-opioid analgesics (vs. not taking). The UWS flow rate was lower in patients taking antidepressants (vs. not taking) (0.16 vs. 0.22 ml/min p = .002) and higher (and within normal range) in patients taking sex hormones (vs. not taking) (0.25 vs. 0.16 ml/min; p = .005). On the other hand, SWS was lower in patients taking corticosteroid (vs. not taking) (0.76 vs. 1.07 ml/min; p = .002), and in patients taking DMARDs (vs. not taking) (0.71 vs. 0.98 ml/min; p = .021). Finally, differences in medians of both UWS and SWS were statistically significant in patients taking 1 or more than 1 opioid analgesic (vs. not taking, p ≤ .0001 and p = .031, respectively), 1 or more than 1 anticonvulsants (vs. not taking, p = .008 and p = .007), 1 or more than 1 antidepressants (vs. not taking, p < .0001 for both), 1 or more than 1 DMARDs (vs. not taking, p = .042, and p = .003). CONCLUSIONS: A greater negative impact on UWS and SWS flow rates was seen in patients taking more than one medication from the same drug class. Intake of antidepressants, corticosteroids and DMARDs is associated with lower whole saliva flow rates. CLINICAL RELEVANCE: Salivary flow rate can be modified by some specific medications, mostly by polypharmacy.

Salivary gland involvement and oral health in patients with coeliac disease.

Coeliac disease (CD) is a chronic immune-mediated enteropathy triggered by ingestion of gluten. The aim of this study was to investigate if the salivary glands as a component of the mucosal immune system are involved in CD, leading to sialadenitis and salivary gland dysfunction and associated oral manifestations. Twenty patients with CD aged 49.2 (SD 15.5 years) and 20 age- and gender-matched healthy controls underwent an interview regarding general and oral health, serological analysis, a clinical oral examination including bitewing radiographs, Candida smear, assessment of salivary mutans streptococci and lactobacilli levels, unstimulated and chewing-stimulated whole and parotid saliva flow rates, analysis of secretory IgA, and a labial salivary gland biopsy. Xerostomia, mucosal lesions, dry/cracked lips and focal lymphocytic sialadenitis were more prevalent and extensive in patients with CD than in healthy controls. Moreover, the patients had less gingival inflammation and higher whole saliva flow rates than the healthy controls, but did not differ regarding dental health and levels of cariogenic bacteria and Candida. The major salivary gland function appears unaffected, contributing to maintenance of a balanced microbiota and oral health in CD patients. Xerostomia and labial dryness may be related to minor salivary gland inflammation and subsequent impaired mucosal lubrication.

Efficacy and safety of a novel mucoadhesive clobetasol patch for treatment of erosive oral lichen planus: A phase 2 randomized clinical trial.

BACKGROUND: Oral lichen planus (OLP) is a chronic inflammatory disorder of the oral mucosa. Currently there is no approved treatment for OLP. We report on the efficacy and safety of a novel mucoadhesive clobetasol patch (Rivelin® -CLO) for the treatment of OLP. METHODS: Patients with confirmed OLP and measurable symptomatic ulcer(s) participated in a randomized, double-blind, placebo-controlled, multicenter clinical trial testing a novel mucoadhesive clobetasol patch (Rivelin® -CLO) in OLP across Europe, Canada, and the United States. Patients were randomized to placebo (nonmedicated), 1, 5, 20 µg Clobetasol/patch, twice daily, for 4 weeks. The primary endpoint was change in total ulcer area compared to baseline. Secondary endpoints included improvement from baseline in pain, disease activity, and quality of life. RESULTS: Data were analyzed and expressed as mean [SD]. One hundred thirty-eight patients were included in the study; 99 females and 39 males, mean age was 61.1 [11.6] years. Statistical analyses revealed that treatment with 20-µg Rivelin® -CLO patches demonstrated significant improvement with ulcer area (p = 0.047), symptom severity (p = 0.001), disease activity (p = 0.022), pain (p = 0.012), and quality of life (p = 0.003) as compared with placebo. Improvement in OLP symptoms from beginning to the end of the study was reported as very much better (best rating) in the 20-µg group (25/32) patients compared to the placebo group (11/30), (p = 0.012). Adverse events were mild/moderate. Candidiasis incidence was low (2%). CONCLUSIONS: Rivelin® -CLO patches were superior to placebo demonstrating statistically significant, clinically relevant efficacy in objective and subjective improvement and, with a favorable safety profile.

Gluten-free diet modulates inflammation in salivary glands and pancreatic islets.

OBJECTIVES: A lifelong gluten-free (GF) diet ameliorates autoimmune diabetes in non-obese diabetic (NOD) mice and most likely in humans. Besides diabetes, NOD mice develop focal sialadenitis, as seen in Sjögren's syndrome (SS). In humans, type 1 diabetes (T1D) is also linked to SS. Here, we investigated whether a lifelong GF diet influences the immune cell infiltration in the salivary glands and pancreatic islets in NOD mice. METHODS: NOD mice were fed a lifelong (i.e. 13 weeks) GF or gluten-containing standard (STD) diet. Insulitis and sialadenitis were scored on H&E-stained paraffin-embedded sections of pancreas and submandibular glands. Immune cell specificity and distribution were investigated immunohistochemically. RESULTS: There were fewer CD68+ and CD4+ cells in submandibular gland areas with focal sialadenitis as well as reduced insulitis and fewer VEGFR2+ cells in pancreatic islets in mice on GF versus STD diet. The degree of sialadenitis was not significantly lower in GF mice, but sialadenitis and insulitis correlated strongly. Lung weight was lower in GF mice. CONCLUSION: In NOD mice, a lifelong GF diet reduces infiltration of monocytes/macrophages and T cells in salivary glands and inflammation in pancreatic islets, possibly by reducing VEGFR2, indicating that the linked autoimmune diseases, T1D and SS, may be alleviated by a GF diet.

[Xerostomia].

Xerostomia and salivary gland hypofunction impact oral health and quality of life and are mainly caused by the intake of medications, chronic disorders like Sjögren's syndrome, and head and neck radiation. Other aetiologies may be local diseases of the salivary glands including infections, cancer, or obstructive diseases of the salivary ducts. Management strategies are primarily alleviating symptoms. Current investigations show promising results in stem cell treatment. In this review, we want to provide comprehension of the aetiologies, evaluation, and management of xerostomia and hyposalivation.

Older age, smoking, tooth loss and denture-wearing but neither xerostomia nor salivary gland hypofunction are associated with low intakes of fruit and vegetables in older Danish adults.

Xerostomia and salivary gland hypofunction are prevalent conditions in older people and may adversely influence the intake of certain foods, notably fruit and vegetables. Here, we aimed to investigate whether xerostomia and salivary gland hypofunction were associated with a lower intake of fruit and vegetables. The study included 621 community-dwelling adults, mean age 75⋅2 ± 6⋅4 years, 58⋅9 % female, who had participated in the Copenhagen City Heart Study follow-up, and undergone interviews regarding food intake (preceding month), oral and general health (xerostomia, taste alterations, diseases, medication, alcohol consumption and smoking), clinical oral examination and measurements of unstimulated and chewing-stimulated whole saliva flow rates. The average total energy intake (8⋅4 ± 2⋅7 MJ) and protein energy percentage (14⋅8 ± 3⋅1 %) were slightly below recommendations. The average fruit (234⋅7 ± 201⋅2 g/d) and vegetables (317⋅3 ± 157⋅4 g/d) intakes were within recommendations. Xerostomia and hyposalivation were more prevalent in women than in men (16⋅4 v. 7⋅1 %, P < 0⋅001 and 40⋅7 v. 27⋅5 %, P < 0⋅001). Multiple linear regression analyses revealed that older age (ß -0⋅009, se 0⋅003, P = 0⋅005), smoking (ß -0⋅212, se 0⋅060, P = 0⋅0005) and wearing complete dentures/being partially or fully edentulous (ß -0⋅141, se 0⋅048, P = 0⋅003), but neither xerostomia nor salivary flow rates were associated with an inadequate fruit and vegetable intake, after adjustment for covariates. Older age, smoking, tooth loss and denture-wearing were stronger determinants of low fruit and vegetable intakes than xerostomia and salivary hypofunction supporting the importance of dietary counselling and maintenance of oral health and an adequate masticatory performance.

Value of multilevel sectioning of labial salivary gland biopsies in the diagnosis of Sjögren's syndrome.

OBJECTIVES: The objective of this study was to examine the diagnostic value of cutting labial salivary gland (LSG) biopsies at 2 levels in the histological evaluation for Sjögren's syndrome (SS). STUDY DESIGN: This retrospective study included LSG biopsy specimens from 112 consecutive patients evaluated for SS from 2007 to 2019. Three observers, blinded with regard to patient data, independently scored the degree of focal lymphocytic infiltration (foci) and calculated the focus score in specimens cut at 2 levels 60 µm apart. RESULTS: Unblinded analysis revealed that the LSG specimens derived from 107 women and 5 men, aged 49.2 ± 22.3 years. Seventy-six patients had SS (70 primary SS and 6 secondary SS) according to the American-European Consensus Group and American College of Rheumatology/European League Against Rheumatism criteria. The average number of LSGs was 5.0 ± 1.4 and the focus scoring area was 16.1 ± 7.6 mm2. Compared to baseline, the average number of foci (4.4 vs 5.1, P < .001), focus score (1.7 vs 1.9, P = .01), and cases with focus score >1.0 (61 vs 74%; P = .03) were higher in the second level. Subsequently, an additional 11 cases of SS were confirmed (14%), and 8 non-SS cases were reclassified as SS (22%). CONCLUSIONS: Histological assessment of an additional section level improves the diagnostic accuracy of the labial salivary gland biopsy to detect histopathological changes consistent with the diagnosis of SS.

Distinct microRNA expression profiles in saliva and salivary gland tissue differentiate patients with primary Sjögren's syndrome from non-Sjögren's sicca patients.

OBJECTIVES: Increasing evidence suggests that aberrant expression of microRNAs (miRNAs) is involved in the pathogenesis of primary Sjögren's syndrome (pSS). The aim was thus to characterize the miRNA profile in saliva, salivary gland tissue, and plasma from patients with pSS and compare findings with those of patients having Sjögren-like disease (non-pSS). In addition, to correlate miRNA levels and clinicopathological features of pSS. METHODS: miRNA real-time quantitative polymerase chain reaction was performed on saliva, plasma, and salivary gland tissue samples from 24 patients with pSS and 16 non-pSS in 384-well plates. T test was used for comparison of miRNA profiles, followed by Benjamini-Hochberg correction. The discriminatory power of miRNAs was evaluated by receiver-operating characteristic curves, and Pearson/Spearman correlation was used for correlation analyses. RESULTS: In saliva, 14 miRNAs were significantly differentially expressed between pSS and non-pSS, including downregulation of the miR-17 family in pSS. In salivary gland tissue of patients with pSS, miR-29a-3p was significantly upregulated. Plasma miRNAs did not differ between the two groups, although the miR-17 family tended to be downregulated. The combination of miR-17-5p and let-7i-5p in saliva yielded an area under curve of 97% (CI 92%-100%). Several miRNAs correlated significantly with one another and with salivary flow rates and histopathology. CONCLUSION: Our findings indicate that the miRNA expression profile in saliva may enable to discriminate between pSS and non-pSS patients. However, further validation in larger cohorts is needed as well as functional analyses of the miRNAs of interest.

Effect of Lozenges Containing Lactobacillus reuteri on the Severity of Recurrent Aphthous Ulcers: a Pilot Study.

To investigate the effect of a probiotic supplement on the severity of aphthous lesions in patients with recurrent aphthous stomatitis (RAS) over a 3-month period. A second endpoint was to study the effect on pain related to the lesions. The study employed a double-blind randomized, placebo-controlled design with two parallel arms. Twenty patients with minor and major RAS were consecutively enrolled and randomly assigned to the test or the control group. The intervention consisted of lozenges containing two strains of Lactobacillus reuteri taken twice daily for 90 days. Ulcer Severity Score (USS) consisting of six lesion characteristics (number, size, duration, ulcer-free period, site, and pain) was calculated at baseline and after the intervention. Oral pain related to the lesions was estimated by the patients with a Visual Analogue Pain Scale. An improvement of the USS, as well as oral pain, was evident in both groups after 90 days but the reduction was only statistically significant (p < 0.05) compared with baseline in the test group. There were no significant differences between the groups, neither at baseline nor at follow-up. No side effects were recorded. Daily supplements with L. reuteri reduced the severity of aphthous lesions over a 90-day period but the improvement was not significantly better than placebo. The results encourage further research and provide a basis for power calculations of larger and extended studies. ClinicalTrials.gov Identifier: NCT02976922.

Characterization of burning mouth syndrome profiles based on response to a local anaesthetic lozenge.

OBJECTIVE: Burning mouth syndrome (BMS) is a chronic oral pain condition with unknown aetiology but assumed to involve peripheral/central neuropathological and immune-mediated inflammatory factors. We aimed at characterizing inflammatory and neurogenic profiles and oral symptomatology of patients with BMS based on response to a local anaesthetic lozenge. METHODS: Patients with BMS were divided into an Effect (n = 13), No effect (n = 8) or Unspecified (n = 2) group according to their response to a local anaesthetic lozenge on oral pain. Inflammation was assessed in blood plasma and saliva by analyses of IL-6, IL-8, IL-17A, IL-23 and TNF-α levels. The degree of inflammation and distribution of oestrogen receptor, NGF, NGF-receptor, TRPV-1 and IL-17F in buccal mucosal tissue were investigated by immunohistochemistry. RESULTS: Immunoreactivity to the oestrogen receptor was most intense in the Effect group, whereas the No effect group tended to have higher plasma levels of the pro-inflammatory cytokines. CONCLUSIONS: Our findings indicate that the response to treatment with local anaesthesia enables subgrouping of patients with BMS according to the potential pathogenic mechanisms. Effect of local anaesthesia indicates a peripheral neuropathology involving lack of oestrogen and upregulation of oestrogen receptors, and no effect indicates a systemic inflammation-induced mechanism leading to increased levels of plasma cytokines.

Next-generation sequencing of whole saliva from patients with primary Sjögren's syndrome and non-Sjögren's sicca reveals comparable salivary microbiota.

Objective: To characterize and compare the salivary microbiota in patients with pSS and patients with non-Sjögren's-related sicca, and to relate the findings to their oral health status and saliva flow rates. Methods: Twenty-four patients fulfilled the 2016 classification criteria for pSS and 34 did not (non-pSS). A clinical examination included registration of decayed, missing and filled teeth/-surfaces and collection of whole saliva. The microbiota was characterized using next-generation sequencing of the V1-V3 region of the 16S rRNA gene. Data were annotated against the eHOMD database. Results: A total of 509 different bacterial taxa were identified. There were no statistically significant differences between the groups with regard to the abundance of predominant genera, bacterial diversity and relative abundance on the genus or species level. The two groups did not differ with regard to general health, including intake of xerogenic medication and polypharmacy, oral health status or unstimulated and stimulated whole saliva flow rates. Conclusion: The salivary microbiota and oral health status, as well as salivary flow rate in patients with pSS resemble that of non-pSS patients. Our findings indicate that changes in the salivary microbiota do not appear to be determined by the disease entity pSS itself.

Probiotic supplements containing Lactobacillus reuteri does not affect the levels of matrix metalloproteinases and interferons in oral wound healing.

OBJECTIVE: The use of beneficial bacteria may stimulate wound healing. We performed a randomized, placebo-controlled double-blind cross-over study comprising ten healthy volunteers. The aim was to investigate the impact of topical and systemic applications of probiotic lactobacilli (Lactobacillus reuteri) on the healing of standardized wounds (punch biopsies) in the oral mucosa. The expression of selected matrix metalloproteinases (MMP'S) and interferons (IFN's) was analyzed with multiplex immunoassays in the wound exudate during the first healing week (day 2, 5 and 8). RESULTS: All participants completed the study and in all cases, the healing after the punch biopsies was uneventful. The concentrations of MMP-1, MMP-2, MMP-3 decreased with time in both the test- and control group. The MMP levels were consistently lower during the probiotic intervention when compared with placebo but the differences were not statistically significant. Likewise, the concentrations if IFN-alpha2, IFN-beta and IFN-gamma decreased with time with no significant differences between the test and placebo interventions. Within the limitations of this pilot study, we were unable to demonstrate an influence of probiotic supplements containing L. reuteri on the concentrations of selected matrix metalloproteinases and interferons from mucosal wounds within 1 week after a standardized punch biopsy. Trial registration ClinicalTrials.gov Identifier NCT03210779. Date of registration: July 7, 2017.

Mucin dispersions as a model for the oromucosal mucus layer in in vitro and ex vivo buccal permeability studies of small molecules.

The mucus layer is believed to play a part in drug permeation across the oral mucosa. Human freeze-dried saliva (HFDS) and porcine gastric mucin (PGM) was evaluated as model for mucus layer per se or in conjunction with in vitro and ex vivo buccal permeability models. Four small molecules (nicotine, mannitol, propranolol, caffeine) showed decreased permeability across mucin dispersions, compared to controls, and a greater effect was seen with HFDS than with PGM. Permeability of propranolol and caffeine across filter-grown TR146 cells was decreased by the presence of mucin, whereas no effect was found on nicotine and mannitol. Incubation of porcine buccal mucosa with mucin dispersions for 24 h compromised the integrity of the tissue, whereas 30 min incubation did not affect tissue integrity. Tissue incubation with mucin dispersions did not decrease nicotine permeability. For the studied model drugs, it is concluded that mucin dispersions constitute a minor barrier for drug diffusion compared to the epithelium.

Oral symptoms and salivary findings in oral lichen planus, oral lichenoid lesions and stomatitis.

BACKGROUND: To examine if patients with oral lichen planus, oral lichenoid lesions and generalised stomatitis and concomitant contact allergy have more frequent and severe xerostomia, lower unstimulated and chewing-stimulated saliva and citric-acid-stimulated parotid saliva flow rates, and higher salivary concentration of total protein and sIgA than cases without contact allergy and healthy controls. METHODS: Forty-nine patients (42 women, aged 61.0 ± 10.3 years) and 29 healthy age- and gender-matched subjects underwent a standardised questionnaire on general and oral health, assessment of xerostomia, clinical examination, sialometry, mucosal biopsy and contact allergy testing. RESULTS: Nineteen patients had oral lichen planus, 19 patients had oral lichenoid lesions and 11 patients had generalised stomatitis. 38.8% had contact allergy. Xerostomia was significantly more common and severe in patients (46.9%) than in healthy controls, whereas the saliva flow rates did not differ. The patients had higher sIgA levels in unstimulated and chewing-stimulated saliva than the healthy controls. The total protein concentration in saliva was lower in the unstimulated saliva samples whereas it was higher in the chewing stimulated saliva samples from patients when compared to healthy controls. The differences were not significant and they were irrespective of the presence of contact allergy. CONCLUSION: Xerostomia is prevalent in patients with oral lichen planus, lichenoid lesions and generalised stomatitis, but not associated with salivary gland hypofunction, numbers of systemic diseases or medications, contact allergy, age, or gender. Salivary sIgA levels were higher in patients than in healthy controls, but did not differ between patient groups. The total salivary protein concentration was lower in unstimulated saliva samples and higher in chewing-stimulated saliva samples in patients than in healthy controls, but did not differ between patient groups. Our findings do not aid in the discrimination between OLP and OLL and these conditions with or without contact allergic reactions.