Xerostomia/Salivary Gland Hypofunction: Diagnosis and Management.

The patient with xerostomia (sensation of dry mouth) or inadequate saliva (salivary gland hypofunction) may present with a wide range of clinical signs and symptoms affecting the oral cavity and systemic health. Recognition of these clinical presentations allows the dental healthcare professional to perform objective tests to identify the status of salivary gland function. Based on these results, recommendations for treatment using over-the-counter and prescription medications can be made. This article discusses clinical indications related to salivary gland hypofunction, testing methodologies, and treatment approaches.

Epithelial expression of keratinocytes growth factor in oral precancer lesions.

BACKGROUND: Keratinocyte growth factor (KGF) is a potent epithelial mitogen that acts by binding the KGF receptors (KGFRs) expressed on epithelial cells and regulates proliferation and differentiation. The objective of this study was to investigate the expression of KGF in the epithelium in oral precancer. MATERIALS AND METHODS: Archival tissues of oral submucous fibrosis (SMF) and leukoplakia were assessed for epithelial KGF expression by immunohistochemistry and real-time quantitative polymerase chain reaction. RESULTS: KGF was predominantly expressed in the basal and parabasal cells in the epithelium of SMF tissues. KGF transcript in the epithelial cells increased with increasing severity of epithelial dysplasia in oral leukoplakia. CONCLUSION: Although widely reported as a product secreted by the mesenchymal cells, our data suggest that the KGF is also expressed in oral epithelial cells much like the expression in ovarian epithelial cells. Based on the localization of KGF in cells at the epithelial mesenchymal junction and that of the reported presence of KGFR in oral keratinocytes, a potential mechanism involving paracrine and autocrine interactions of KGF and KGFR in early stages of oral precancer is postulated.

Intraoral electrostimulator for xerostomia relief: a long-term, multicenter, open-label, uncontrolled, clinical trial.

OBJECTIVE: A previous sham-controlled multinational study demonstrated the short-term efficacy and safety for xerostomia treatment of an intraoral device that delivers electrostimulation to the lingual nerve. The objective of this study was to test the hypothesis that those beneficial effects would be sustained over an 11-month period. STUDY DESIGN: The device was tested on a mixed sample of 94 patients with xerostomia in an open-label, uncontrolled, prospective multicenter trial. Statutory outcome assessments were done at 5th, 8th, and 11th months and analyzed by multiple comparisons. RESULTS: Improvements achieved at month 5 from baseline were sustained throughout the follow-up period for the primary outcome, xerostomia severity, and the secondary outcomes resting whole salivary flow rate, xerostomia frequency, oral discomfort, and difficulties in speech, swallowing, and sleeping. No significant side effects were detected. CONCLUSIONS: The beneficial effects of a removable intraoral electrostimulating device were sustained for an 11-month period.

Differential expression of TLR-2 and TLR-4 in the epithelial cells in oral lichen planus.

OBJECTIVE: Oral lichen planus (OLP) is a chronic inflammatory condition of the mucosa mediated by a complex signalling network between the keratinocytes and the sub-epithelial lymphocytes. Since OLP occurs in constantly renewing epithelium continuously exposed to commensals, we hypothesised that the epithelial cell microflora interactions may mediate the persistent inflammation. By virtue of their ability to respond to most oral commensal microorganisms, the toll like receptor-2 (TLR-2) and TLR-4 are the most widely investigated receptors in oral diseases. The overall objective of this study was to investigate the role of TLR-2 and TLR-4 in OLP. DESIGN: Systemically healthy OLP and control subjects were recruited after obtaining the institutional review board approval. Expression of TLR-2 and TLR-4 proteins and transcripts in the tissue epithelium and in the epithelial cells isolated from saliva were determined by immunohistochemistry and quantitative real-time polymerase chain reaction respectively. RESULTS: The tissue epithelium and the salivary epithelial cells expressed reduced TLR-2 and increased TLR-4 proteins and transcripts in OLP. The salivary epithelial cells from OLP subjects secreted elevated IL-12. However, upon stimulation with bacterial lipopolysaccharide the epithelial cells from OLP exhibited a mixed Th1 (IL-12) and Th2 (IL-4) response. Presence of dexamethasone significantly reduced inflammatory cytokines in the in vitro stimulated cultures of salivary epithelial cells from OLP subjects. CONCLUSION: Collectively, our data support a critical role for the host-microbial interactions in the OLP pathogenesis. The potential use of exfoliated oral epithelial cells in saliva for functional analysis exponentially increases its value as biological specimen for clinical research.

Quality assessment of saliva bank samples.

INTRODUCTION: Biospecimens, such as urine, blood, saliva, tissue, cells, DNA, RNA, and protein, are biological material to be stored in a biorepository. They constitute critical resources of molecular data for basic and translational research integrated with diagnostic, therapeutics, and prevention of human diseases. The reliability of the molecular data is dependent on the quality and the consistency of the biospecimen being analyzed. The potential of human saliva as a valuable diagnostic fluid for oral and systemic conditions is being increasingly recognized. The aim of this study is to determine the molecular quality of unstimulated whole saliva (UWS) samples stored over a period of 1 to 5 years. MATERIALS AND METHODS: UWS samples collected between 2006 and 2010 (20/year) and stored at -80°C were assessed for molecular integrity. The study was approved by the institutional review board of the Indiana University Purdue University at Indianapolis. Qualitative and quantitative measurements of salivary proteins were determined by gel electrophoresis and spectrophotometry. The salivary nucleic acid content was determined by the Nanodrop method and genetic analysis. The nature of the cellular sediment in the UWS was determined by amplification of specific gene. RESULTS: No significant differences were observed in the amount of proteins, nucleic acid, or in the number of viable cells in the UWS samples stored for 1 to 5 years. CONCLUSION: Archived UWS samples could function as excellent biospecimen resources for measurement of protein, DNA, and RNA analytes, and act as an efficient source for human epithelial cells.

Efficacy and safety of an intraoral electrostimulation device for xerostomia relief: a multicenter, randomized trial.

OBJECTIVE: To evaluate the efficacy and safety of an intraoral electrostimulation device, consisting of stimulating electrodes, an electronic circuit, and a power source, in treating xerostomia. The device delivers electrostimulation through the oral mucosa to the lingual nerve in order to enhance the salivary reflex. METHODS: The device was tested on a sample of patients with xerostomia due to Sjögren's syndrome and other sicca conditions in a 2-stage prospective, randomized, multicenter trial. Stage I was a double-blind, crossover stage designed to compare the effects of the electrically active device with the sham device, each used for 1 month, and stage II was a 3-month open-label stage designed to assess the long-term effects of the active device. Improvement in xerostomia severity from baseline was the primary outcome measure. RESULTS: A total of 114 patients were randomized. In stage I, the active device performed better than the sham device for patient-reported xerostomia severity (P<0.002), xerostomia frequency (P<0.05), quality of life impairment (P<0.01), and swallowing difficulty (P<0.02). At the end of stage II, statistically significant improvements were verified for patient-reported xerostomia severity (P<0.0001), xerostomia frequency (P<0.0001), oral discomfort (P<0.001), speech difficulty (P<0.02), sleeping difficulty (P<0.001), and resting salivary flow rate (P<0.01). CONCLUSION: Our findings indicate that daily use of the device alleviated oral dryness, discomfort, and some complications of xerostomia, such as speech and sleeping difficulties, and increased salivary output. The results show a cumulative positive effect of the device over the period of the study, from baseline to the end of the trial.

Soluble CD14 and toll-like receptor-2 are potential salivary biomarkers for oral lichen planus and burning mouth syndrome.

Oral lichen planus (OLP) and burning mouth syndrome (BMS) are chronic conditions affecting the oral mucosa characterized by pain and burning sensation. Saliva plays a significant role in the maintenance of physical and functional integrity of normal oral mucosa. Identification of potential "salivary biomarkers" for early diagnosis and/or monitoring of human diseases is being explored. We investigated the soluble forms of innate immune associated proteins CD14 and toll-like receptor-2 in unstimulated whole saliva (UWS) as potential biomarkers for OLP and BMS. Our results suggest that the levels of sCD14 and sTLR-2 in UWS were upregulated in OLP and BMS respectively. In addition, oral epithelial cells in the saliva of patients with OLP and BMS exhibited elevated levels of CD14 mRNA and decreased levels of TLR-2 mRNA. Interestingly, presence of co-existent oral candidiasis nullified these changes.

Suppression of immune responses in collagen-induced arthritis by a rationally designed CD80-binding peptide agent.

OBJECTIVE: The CD80/CD86-CD28/CD152 costimulatory pathways transmit signals for CD4+ T cell activation and suppression and are critically involved in the pathogenesis of rheumatoid arthritis (RA). A significant number of CD4+ T cells and macrophages in the rheumatoid synovium express elevated levels of CD80, increasing the potential for costimulation in trans of naive T cells. To determine the effect of blockade of this costimulatory axis in RA, we designed novel CD80-binding peptides and evaluated their therapeutic potential in collagen-induced arthritis (CIA), an animal model of RA. METHODS: The conserved MYPPPY motif of CD152 adopts a polyproline type II (PPII) helical conformation in the CD80-CD152 complex. The pairing preferences of the critical residues at the CD80-CD152 interface and their propensity to form PPII helices were integrated to design peptides with optimum PPII helical content that selectively block CD80-receptor interactions. The clinical efficacy was tested in DBA/1LacJ mice that were administered the CD80 blocking agents, called CD80-binding competitive antagonist peptides (CD80-CAPs), at the time of immunization with bovine type II collagen or 3 weeks after immunization. RESULTS: A single administration of select CD80-CAPs significantly reduced the clinical, radiologic, and histologic disease severity in CIA. Importantly, administration of CD80-CAPs during activated immune response significantly suppressed disease development by reducing mononuclear cell infiltration in the joints and mediating peripheral deletion of activated CD4+ T cells. CONCLUSION: A rationally designed CD80-binding peptide both prevents and suppresses CIA, suggesting a potential application in RA. Apoptosis of activated CD4+ T cells following in vivo blockade suggests that the effects of CD80-CAPs may be long-lasting.

Papillary squamous cell carcinoma presenting on the gingiva.

BACKGROUND: Papillary squamous cell carcinoma (PSCC) is a rare variant of squamous cell carcinoma. PSCC can occur as either an in situ or invasive tumor. The sites of occurrence in order of the most to least prevalent are the larynx, oropharynx, and nasopharynx. We present an unusual case of PSCC occurring on the gingiva. METHODS: A 72-year-old white female presented with a chief complaint of tooth mobility in the right posterior mandible. Clinical examination revealed a Miller's Class 2 mobility of tooth #28 along with an erythematous, papillary appearance of the lingual gingiva on teeth #27, #28, and #29. Her dental history revealed treatment of tooth #28 with locally delivered antibiotics. Her medical history revealed a diagnosis of breast cancer 8 years prior to examination that was treated with partial mastectomy and radiation therapy. An initial differential clinical diagnosis of verrucous carcinoma or metastatic carcinoma was made. RESULTS: Surgical therapy included extraction of tooth #28 and an excisional biopsy of the lesion on the lingual gingiva. Microscopic evaluation of the gingival specimen revealed a neoplastic papillary proliferation of the surface epithelium with a thick layer of parakeratin, deep parakeratin-lined crypts, and a thickened spinous cell layer along with islands and strands of malignant epithelium. The microscopic appearance of the lesion was characteristic for PSSC. The patient's tumor was removed via a block resection that included teeth #27 through #31 and a radical neck dissection. CONCLUSIONS: This is a case report of PSCC occurring on the gingiva. This report demonstrates that, even though oral cancers involving the periodontium are a relatively rare occurrence, periodontists cannot be complacent about the diagnosis of periodontal bone loss. It also highlights the importance of utilizing a histopathologic examination to confirm the clinical diagnosis for any suspicious lesion.

Recurrent aphthous stomatitis.

Recurrent aphthous stomatitis remains a commonly occurring cause of oral pain and ulceration. Although the ulcerations of RAS are multifactorial and of unknown cause, recognition of the role of patient and environmental factors may be helpful in developing recommendations for treatment and prevention of future ulcers.

Comparison of computer-assisted brush biopsy results with follow up scalpel biopsy and histology.

Oral brush biopsy results were compared with scalpel biopsy and histology to determine the positive predictive value of an abnormal brush biopsy finding. Of 243 patients with abnormal brush biopsies, 93 proved positive for dysplasia (79) or carcinoma (14) and 150 were negative for either dysplasia or carcinoma. Therefore, the positive predictive value of an abnormal brush biopsy was 38% (93/243). By using the oral brush biopsy, dentists can inform their patients that abnormal findings have a strong positive predictive value for dysplasia or carcinoma and therefore require follow-up confirmation by scalpel biopsy.