Immunopathogenesis of canine chronic ulcerative stomatitis.

Canine Chronic Ulcerative Stomatitis is a spontaneously occurring inflammatory disease of the oral mucosa. An immune-mediated pathogenesis is suspected though not yet proven. We have recently reported on the clinical and histologic features, and identification of select leukocyte cell populations within the lesion. A clinical and histologic similarity to oral lichen planus of people was proposed. In the present study, these initial observations are extended by examining lesions from 24 dogs with clinical evidence of chronic ulcerative stomatitis. Because dogs with chronic ulcerative stomatitis often have concurrent periodontal disease, we wondered if dental plaque/biofilm may be a common instigator of inflammation in both lesions. We hypothesized that dogs with chronic ulcerative stomatitis would exhibit a spectrum of pathologic changes and phenotype of infiltrating leukocytes that would inform lesion pathogenesis and that these changes would differ from inflammatory phenotypes in periodontitis. Previously we identified chronic ulcerative stomatitis lesions to be rich in FoxP3+ and IL17+ cells. As such, we suspect that these leukocytes play an important role in lesion pathogenesis. The current study confirms the presence of moderate to large numbers of FoxP3+ T cells and IL17+ cells in all ulcerative stomatitis lesions using confocal immunofluorescence. Interestingly, the majority of IL17+ cells were determined to be non-T cells and IL17+ cell frequencies were negatively correlated with severity on the clinical scoring system. Three histologic subtypes of ulcerative stomatitis were determined; lichenoid, deep stomatitis and granulomatous. Periodontitis lesions, like stomatitis lesions, were B cell and plasma cell rich, but otherwise differed from the stomatitis lesions. Direct immunofluorescence results did not support an autoantibody-mediated autoimmune disease process. This investigation contributes to the body of literature regarding leukocyte involvement in canine idiopathic inflammatory disease pathogenesis

Meta-analysis of stomatitis in clinical studies of everolimus: incidence and relationship with efficacy.

BackgroundEverolimus, an oral mammalian target of rapamycin (mTOR) inhibitor, is used to treat solid tumors and tuberous sclerosis complex (TSC). Stomatitis, an inflammation of the mucous membranes of the mouth, is a common adverse event associated with mTOR inhibitors, including everolimus. We conducted a meta-analysis of data from seven randomized, double-blind phase 3 clinical trials of everolimus to determine the clinical impact of stomatitis on efficacy and safety.Patients and methodsData were pooled from the safety sets of solid tumor [breast cancer (BOLERO-2 and BOLERO-3), renal cell carcinoma (RECORD-1), carcinoid tumors (RADIANT-2), and pancreatic neuroendocrine tumors (RADIANT-3)] and TSC studies (EXIST-1 and EXIST-2). Data from solid tumor trials and TSC trials were analyzed separately.ResultsThe rate of stomatitis was 67% in the solid tumor trials (973/1455 patients) and 70% in the TSC trials (110/157 patients). Most stomatitis events were grade 1/2, with grade 3/4 events reported in only 9% (solid tumor trials) and 8% (TSC trials) of patients. Low TSC patient numbers prevented an in-depth evaluation of stomatitis and response. In the solid tumor trials, most first stomatitis episodes (89%; n = 870) were observed within 8 weeks of starting everolimus. Patients with stomatitis occurring within 8 weeks of everolimus initiation had longer progression-free survival (PFS) than everolimus-treated patients without stomatitis in BOLERO-2 {8.5 versus 6.9 months, respectively; hazard ratio (HR), 0.78 [95% confidence interval (CI), 0.62-1.00]} and RADIANT-3 [13.9 versus 8.3 months, respectively; HR, 0.70 (95% CI, 0.48-1.04)]. A similar trend was observed in RECORD-1 [HR, 0.90 (95% CI, 0.66-1.22)] and RADIANT-2 [HR, 0.87 (95% CI, 0.61-1.22)] but not in BOLERO-3 [HR, 1.01 (95% CI, 0.75-1.36)].ConclusionsStomatitis did not adversely affect PFS, supporting the administration of everolimus in accordance with standard management guidelines

Physical Properties of Denture Base Resins Potentially Resistant to \u3cem\u3eCandida\u3c/em\u3e Adhesion

Purpose: The addition of anionic charge on denture base resins has been shown to inhibit Candida albicans adhesion and to facilitate adsorption of salivary defense molecules. The aim of this study was to evaluate the physical properties of a modified denture base resin for denture fabrication. Materials and Methods: Specimens made from heat polymerizing resin Lucitone 199 were used as the control group. The two experimental groups, E-10 and E-20, had 10% and 20%, respectively, of the monomer substituted with an experimental phosphate-containing monomer. Flexural strength and modulus, water sorption, solubility, and color stability tests were conducted to ensure compliance with ADA specification No. 12. Water diffusion coefficient into the resins and stainability were also assessed. ANOVA and Scheffé tests were performed for statistical significance. Results: There was an overall decline in all properties with the addition of the experimental phosphate compound. The flexural strength and modulus, water sorption and solubility for E-10, as well as the control were, however, within the ADA specifications. The diffusion coefficients were significantly different (p \u3c 0.05) for the three groups. Staining and color specimens showed no significant difference (p \u3e 0.05) among the three groups. Conclusions: Within the limitations of this study, the physical properties of the phosphate denture base resin at 10% should be suitable for denture fabrication based on the properties assessed

Treatment of denture-related stomatitis improves endothelial function assessed by flow-mediated vascular dilation

Introduction: The presence of oral inflammation has recently been linked with the pathogenesis of cardiovascular diseases. While numerous studies have described links between periodontitis and endothelial dysfunction, little is known about the influence of denture-related stomatitis (DRS) on cardiovascular risk. Therefore, the aim of this study was to determine whether the treatment of DRS can lead to improvement of the clinical measures of vascular dysfunction. Material and methods: The DRS patients were treated with a local oral antifungal agent for 3 weeks. Blood pressure, flow-mediated dilatation (FMD) and nitroglycerine-mediated vascular dilatation (NMD) were measured during three study visits: before treatment, one day and two months after conclusion of antifungal therapy. Results: Flow-mediated dilatation measurements showed significant improvement of endothelial function 2 months after treatment (FMD median 5%, 95 CI: 3–8.3 vs. 11%, 95% CI: 8.8–14.4; p < 0.01), while there was no difference in control, endothelium-independent vasorelaxations (NMD; median = 15.3%, 95% CI: 10.8–19.3 vs. 12.7%, 95% CI: 10.6–15; p = 0.3). Other cardiovascular parameters such as systolic (median = 125 mm Hg; 95% CI: 116–129 vs. 120 mm Hg, 95% CI: 116–126; p = 0.1) as well as diastolic blood pressure and heart rate (median = 65.5 bpm, 95% CI: 56.7–77.7 vs. 71 bpm, 95% CI: 66.7–75; p = 0.5) did not change during or after the treatment. Conclusions: Treatment of DRS is associated with improvement of endothelial function. Since endothelial dysfunction is known to precede the development of severe cardiovascular disorders such as atherosclerosis and hypertension, patients should be more carefully screened for DRS in general dental practice, and immediate DRS treatment should be advised

Use of recombinant virus replicon particles for vaccination against Mycobacterium ulcerans disease

Buruli ulcer, caused by infection with Mycobacterium ulcerans, is a necrotizing disease of the skin and subcutaneous tissue, which is most prevalent in rural regions of West African countries. The majority of clinical presentations seen in patients are ulcers on limbs that can be treated by eight weeks of antibiotic therapy. Nevertheless, scarring and permanent disabilities occur frequently and Buruli ulcer still causes high morbidity. A vaccine against the disease is so far not available but would be of great benefit if used for prophylaxis as well as therapy. In the present study, vesicular stomatitis virus-based RNA replicon particles encoding the M. ulcerans proteins MUL2232 and MUL3720 were generated and the expression of the recombinant antigens characterized in vitro. Immunisation of mice with the recombinant replicon particles elicited antibodies that reacted with the endogenous antigens of M. ulcerans cells. A prime-boost immunization regimen with MUL2232-recombinant replicon particles and recombinant MUL2232 protein induced a strong immune response but only slightly reduced bacterial multiplication in a mouse model of M. ulcerans infection. We conclude that a monovalent vaccine based on the MUL2232 antigen will probably not sufficiently control M. ulcerans infection in humans

Candida albicans biofilm heterogeneity does not influence denture stomatitis but strongly influences denture cleansing capacity

Approximately 20  % of the UK population wear some form of denture prosthesis, resulting in denture stomatitis in half of these individuals. Candida albicans is primarily attributed as the causative agent, due to its biofilm -forming ability. Recently, there has been increasing evidence of C. albicans biofilm heterogeneity and the negative impact it can have clinically; however, this phenomenon has yet to be studied in relation to denture isolates. The aims of this study were to evaluate C. albicans biofilm formation of clinical denture isolates in a denture environment and to assess antimicrobial activity of common denture cleansers against these tenacious communities. C. albicans isolated from dentures of healthy and diseased individuals was quantified using real-time PCR and biofilm biomass assessed using crystal violet. Biofilm development on the denture substratum poly(methyl methacrylate), Molloplast B and Ufi-gel was determined. Biofilm formation was assessed using metabolic and biomass stains, following treatment with denture hygiene products. Although C. albicans was detected in greater quantities in diseased individuals, it was not associated with increased biofilm biomass. Denture substrata were shown to influence biofilm biomass, with poly(methyl methacrylate) providing the most suitable environment for C. albicans to reside. Of all denture hygiene products tested, Milton had the most effective antimicrobial activity, reducing biofilm biomass and viability the greatest. Overall, our results highlight the complex nature of denture- related disease, and disease development cannot always be attributed to a sole cause. It is the distinct combination of various factors that ultimately determines the pathogenic outcome

Growth of Pseudotypes of Vesicular Stomatitis Virus with N-Tropic Murine Leukemia Virus Coats in Cells Resistant to N-Tropic Viruses

Formation of pseudotypes between murine RNA tumor viruses and vesicular stomatitis virus (VSV) has been confirmed. Pseudotypes of VSV genomes coated by the surface envelope from an N-tropic tumor virus grew equally well in cells homozygous for either the Fv-1n or Fv-1b alleles. Therefore, the product of the Fv-1 locus, which restricts growth of murine RNA tumor viruses, must act on an intracellular aspect of tumor virus replication, a step after attachment and penetration

A multicenter experience using adipose-derived mesenchymal stem cell therapy for cats with chronic, non-responsive gingivostomatitis.

BackgroundThe ability of mesenchymal stem cells (MSCs) to modulate immune responses inspired a series of clinical trials addressing oral mucosal inflammation. We previously reported on the safety and efficacy of fresh, allogeneic and autologous, adipose-derived mesenchymal stem cells (ASCs) to treat feline gingivostomatitis (FCGS), an oral mucosal inflammatory disease that shares similarities with human oral lichen planus.MethodsTo meet clinical demand and goals for future commercialization, we determined the feasibility of shipping fresh ASCs to distant clinics and extended our pilot studies to expand safety and efficacy data for shipped and non-shipped ASCs in a cohort of 18 FCGS cats enrolled locally and at a few different locations within the USA.ResultsWe found that ASCs retained their viability, phenotype, and function after shipment. ASCs administered systemically resulted in a 72% positive response rate, identical to that noted in our previous studies. Cats that responded to ASC therapy had a significant decrease in circulating globulin concentration and histological evidence of decreased CD3+ T cells and CD20+ B cells in the oral mucosa. Responder cats also had significantly decreased percentages of CD8lo cells in blood prior to and at 3 months post-ASC therapy. CD8lo cells may serve as a potential "predictor" for response to systemic ASC therapy.ConclusionFresh feline ASCs can be successfully shipped and administered to cats with FCGS. ASCs modulate the immune response and demonstrate efficacy for chronic oral mucosal inflammatory lesions that are characterized by CD8+ T cell inflammation and T cell activation. FCGS is a potentially useful naturally occurring large animal model of human oral inflammatory diseases

Staff-led interventions for improving oral hygiene in patients following stroke

Background For people with limitations due to neurological conditions such as stroke, the routine practice of oral care may become a challenge. Evidence-based supported oral care intervention is essential for this patient group. Objectives To compare the effectiveness of staff-led oral care interventions with standard care for ensuring oral hygiene for individuals after a stroke. Search strategy We searched the trials registers of the Cochrane Stroke Group and Oral Health Group (August 2005), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 1, 2006), MEDLINE (1966 to February 2006), CINAHL (1982 to February 2006), Research Findings Electronic Register (February 2006), National Research Register (Issue 1, 2006), ISI Science and Technology Proceedings (August 2005), Dissertation Abstracts and Conference Papers Index (August 2005). We scanned reference lists from relevant papers and contacted authors and researchers in the field. Selection criteria We identified randomised controlled trials that evaluated one or more interventions designed to improve oral hygiene. Trials based on a mixed population were included, provided it was possible to extract the data specific to the individuals post stroke. Data collection and analysis Two review authors independently classified identified trials according to the inclusion and exclusion criteria, assessed the trial quality and extracted data. Clarification was sought from study authors when required. Main results Eight eligible randomised controlled trials were identified but only one provided stroke-specific information. It compared an oral health care education training programme (OHCE) delivered to nursing home care assistants to delayed training intervention in the control group. Comparisons were made at one and six months after the intervention, using the primary outcome measures dental plaque and denture plaque, and three secondary outcomes. The data available for the 67 individuals with a stroke (obtained from the larger cluster randomised controlled trial) showed that denture plaque scores were significantly reduced up to six months (P &lt; 0.00001) after the intervention. Staff knowledge (P = 0.0008) and attitudes (P = 0.0001) towards oral care also improved significantly. Authors' conclusions Based on one study with a small number of stroke survivors, providing oral care training for carers in a nursing home setting improves their knowledge of and attitudes towards the provision of oral care. In turn, residents' dentures were cleaner, though other oral hygiene measures did not change. Further evidence relating to oral care interventions is severely lacking, in particular with reference to care in hospital for those following stroke. This review is published as a Cochrane Review in the Cochrane Database of Systematic Reviews 2011, Issue 7. Cochrane Reviews are regularly updated as new evidence emerges and in response to comments and criticisms, and the Cochrane Database of Systematic Reviews should be consulted for the most recent version of the Review.</p

The oral microbiome of denture wearers is influenced by natural dentition

Objectives: The composition of dental plaque has been well defined, whereas currently there is limited understanding of the composition of denture plaque and how it directly influences denture related stomatitis (DS). The aims of this study were to compare the microbiomes of denture wearers, and to understand the implications of these towards inter-kingdom and host-pathogen interactions within the oral cavity. Methods: Swab samples were obtained from 123 participants wearing either a complete or partial denture; the bacterial composition of each sample was determined using bar-coded illumina MiSeq sequencing of the bacterial hypervariable V4 region of 16S rDNA. Sequencing data processing was undertaken using QIIME, clustered in Operational Taxonomic Units (OTUs) and assigned to taxonomy. The dentures were sonicated to remove the microbial flora residing on the prosthesis, sonicate was then cultured using diagnostic colorex Candida media. Samples of unstimulated saliva were obtained and antimicrobial peptides (AMP) levels were measured by ELISA. Results: We have shown that dental and denture plaques are significantly distinct both in composition and diversity and that the oral microbiome composition of a denture wearer is variable and is influenced by the location within the mouth. Dentures and mucosa were predominantly made up of Bacilli and Actinobacteria. Moreover, the presence of natural teeth has a significant impact on the overall microbial composition, when compared to the fully edentulous. Furthermore, increasing levels of Candida spp. positively correlate with Lactobacillus spp. AMPs were quantified, though showed no specific correlations. Conclusions: This is the first study to provide a detailed understanding of the oral microbiome of denture wearers and has provided evidence that DS development is more complex than simply a candidal infection. Both fungal and bacterial kingdoms clearly play a role in defining the progression of DS, though we were unable to show a defined role for AMPs