Oral mucosal pellicle as an immune protection against micro-organisms in patients with recurrent aphthous stomatitis: A hypothesis.

Recurrent Aphthous Stomatitis (RAS) is the most common ulcerative diseases of oral mucosa affecting an estimate of 20% of the world's population. Majority of the people affected by RAS are under 30 years of age. RAS is located on the lining (non-keratinized) oral mucosa, i.e. buccal mucosa, lateral side of the tongue, soft palate, lip mucosa, or the floor of mouth. An aphthous ulcer develops when lymphocytic cells infiltrate into the epithelium and cause an edema due to transient inflammatory stimuli. Bacteria, viruses and fungi have been suggested to cause aphthous lesions, but findings regarding oral pathogens are conflicting. Prior consensus has been that RAS is a multifactorial condition, with microbes, allergies, nutritional deficiencies, genetic factors, certain illnesses, immunodeficiency, hormonal changes, trauma and stress among others, contributing to the condition. In spite of many suggestions and investigations, the etiology and pathophysiology of RAS remains uncertain. Our hypothesis focuses on mucin proteins that have been shown to play a role in the formation of protective mucosal pellicle, which serves as the first line of defense between oral epithelium and pathogens within the oral cavity. Mucins, including transmembrane mucin 1 (MUC1), and salivary mucins MUC5B and MUC7 form a protein network that is strongly retained to oral epithelium. The role of the mucosal pellicle in pathophysiology of RAS is unknown. Structural variations have been found in the salivary MUC7 terminal end oligosaccharides in RAS patients, rendering the protein unable to agglutinate pathogens. Furthermore, low levels of MUC1 fail to provide a scaffold for assembly of salivary mucins. We introduce a new hypothesis, the alterations in the structure of these glycoproteins could have a profound impact on the oral mucosal barrier function. On the other hand, micro-organisms secreting their mucolytic enzymes destroy the mucosal pellicle causing oral ulcers.

Salivary metabolomics in the diagnosis of oral cancer and periodontal diseases.

Metabolomics is a systemic study of metabolites, which are small molecules generated by the process of metabolism. The metabolic profile of saliva can provide an early outlook of the changes associated with a wide range of diseases, including oral cancer and periodontal diseases. It is possible to measure levels of disease-specific metabolites using different methods as presented in this study. However, many challenges exist including incomplete understanding of the complicated metabolic pathways of different oral diseases. The review concludes with the discussion on future perspectives of salivary metabolomics from a clinician point of view. Salivary metabolomics may afford a new research avenue to identify local and systemic disorders but also to aid in the design and modification of therapies. A MEDLINE search using keywords "salivary metabolomics" returned 23 results in total, of which seven were omitted for being reviews or letters to the editor. The rest of the articles were used for preparation of the review, 13 of these were published in the last 5 years.

Microplicae--Specialized Surface Structure of Epithelial Cells of Wet-Surfaced Oral Mucosa.

The surface structure of the superficial cells of the oral mucosa is decorated with numerous membrane ridges, termed microplicae (MPLs). The MPL structure is typical of the epithelial surfaces that are covered with protective mucus. Cell membrane MPLs are no longer seen as passive consequences of cellular activity. The interaction between MPLs and the mucins has been demonstrated, however the role of MPL structure seen on the upper surface of the oral epithelial cells is speculative. The cell surface is of potentially great significance, as it harbors many markers for refined prognosis and targets for oral mucosal diseases and cancer therapy. With these aspects in mind, we conducted the present review of the MPL structure and function in order to form the basis for further studies of MPLs of the oral epithelial cells.

The defence architecture of the superficial cells of the oral mucosa.

The oral epithelium together with the saliva and its components forms a complex structure which is the first line of defence in the oral cavity. The surface of superficial cells of the oral epithelium contains ridge-like folds, microplicae (MPL), which are typical of the surfaces of areas covered with protective mucus. The role of MPL seen on the upper surface of the oral epithelial cells is still unknown. The salivary mucus gel performs a protective diffusion membrane against harmful substances and this membrane is built up by epithelial cells covered by a highly hydrated and viscous gel, where mucins constitute the scaffold. The interaction between the MPL-structure and the mucins is shown in cornea, so that mucins are expressed on the tips of the MPL of the epithelial cells. We hypothesized that the MPL architecture of oral superficial epithelial cells provides the underlying basis for mucins's protective function as well as in ocular surface. The salivary mucous barrier is required to protect the superficial cells and the MPL-structure together with membrane anchored mucin binding protein (MBP) forms the ground to this mucous barrier. So, oral mucosal barrier complex (OMBC) contains both the MBP-mucin - complex and the MPL-structure of the superficial cells. In the future, studies of the alterations of the salivary mucins and that of the MPL-structure may yield therapeutic opportunities for burning mouth syndrome and perhaps for mucositis causing by irradiation. Focus on cell surface microplication and mucins in oral mucosal biology and oral mucosal diseases is a promising avenue for future research in several ways.

Drug-eluting bioabsorbable stents - an in vitro study.

The aim of this study was to investigate the drug elution properties of novel drug-eluting bioabsorbable stents in vitro with four different drugs: dexamethasone, indomethacin, simvastatin and ciprofloxacin. Braided stents of poly-lactic acid (96l/4d) fibers were coated with a solution containing the appropriate bioabsorbable polymer and drug, with acetone as the solvent. Two different drug concentrations for both non-sterile and gamma sterilized stents were used for dexamethasone and indomethacin. For ciprofloxacin and simvastatin, only one drug dose was used. The stents were placed in sodium-phosphate-buffered saline in a shaking incubator (pH 7.4, +37 degrees C) and the eluted drug was measured periodically using an ultraviolet spectrometer. The drugs were hydrophobic to different degrees, as demonstrated by their various speeds of elution. In general, the higher the drug load in the stent, the faster the drug elution and the more hydrophilic the elution profile. In the cases of dexamethasone, indomethacin and ciprofloxacin, the sterilization decreased the drug elution rate slightly and the elution started earlier. However, in the case of ciprofloxacin, the gamma sterilization increased the drug elution rate slightly. Sustained elution was achieved for all four drugs. It was also evident that both the concentration and the hydrophility of the drug had a great influence on the drug elution profile. Gamma sterilization modified the drug elution profiles of dexamethasone, indomethacin and simvastatin, but had little effect on the drug elution profile of ciprofloxacin compared to three other drugs.

Frequency bands and spatiotemporal dynamics of beta burst stimulation induced afterdischarges in hippocampus in vivo.

Temporal and spatial characteristics of hippocampal neuronal network activation are modified during epileptiform afterdischarges. We developed a beta burst stimulation protocol to investigate subregional variations and substrates of rhythmic population spike discharges in vivo in urethane anesthetized Wistar rat hippocampus with a 14-electrode recording array and extracellular single electrode recordings. Our 64 pulse beta burst stimulation protocol was constructed from electrical pulses delivered at intervals corresponding to beta (14-25 Hz), Delta (2 Hz), and slow (0.5 Hz) frequencies. In each experiment these interleaved pulses were all repeated four times with unchanged intervals. Stimulation of either perforant path or fimbria fornix induced a prolonged afterdischarge pattern peaking at 200 Hz fast, 20 Hz beta, and 2 Hz Delta frequencies. Analysis of variance confirmed that the response pattern of the discharges remained constant regardless of the stimulation beta frequency. Within the afterdischarge the fast frequencies were restricted to independent hippocampal subfields whereas beta and slow frequencies correlated across the subfields. Current source density (CSD) analysis revealed that the original signal propagation through subfields of the hippocampus was compromised during the beta burst stimulation induced afterdischarge. In addition, the CSD profile of the epileptiform afterdischarge was consistently similar across the different experiments. Time-frequency analysis revealed that the beta frequency afterdischarge was initiated and terminated at higher gamma (30-80 Hz) frequencies. However, the alterations in the CSD profile of the hippocampus coincided with the beta frequency dominated discharges. We propose that hippocampal epileptiform activity at fast, beta and Delta frequencies represents coupled oscillators at respectively increasing spatial scales in the hippocampal neuronal network in vivo.

Hippocampus retains the periodicity of gamma stimulation in vivo.

Several behavioral state dependent oscillatory rhythms have been identified in the brain. Of these neuronal rhythms, gamma (20-70 Hz) oscillations are prominent in the activated brain and are associated with various behavioral functions ranging from sensory binding to memory. Hippocampal gamma oscillations represent a widely studied band of frequencies co-occurring with information acquisition. However, induction of specific gamma frequencies within the hippocampal neuronal network has not been satisfactorily established. Using both in vivo intracellular and extracellular recordings from anesthetized rats, we show that hippocampal CA1 pyramidal cells can discharge at frequencies determined by the preceding gamma stimulation, provided that the gamma is introduced in theta cycles, as occurs in vivo. The dynamic short-term alterations in the oscillatory discharge described in this paper may serve as a coding mechanism in cortical neuronal networks.