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.

Bone microarchitecture and turnover in the irradiated human mandible.

OBJECTIVES: The aim of this study was to assess the microarchitecture and turnover in irradiated cancellous mandibular bone and the relation with radiation dose, to elucidate the effects of radiotherapy on the mandible. PATIENTS AND METHODS: Mandibular cancellous bone biopsies were taken from irradiated patients and controls. Micro-CT scanning was performed to analyze microstructural bone parameters. Bone turnover was assessed by histomorphometry. Local radiation dose at the biopsy site (Dmax) was estimated from radiotherapy plans. RESULTS: Twenty-seven irradiated patients and 35 controls were included. Osteoid volume (Osteoid Volume/Bone Volume, OV/BV) [0.066/0.168 (median/interquartile range (IQR), OV/BV; %), P < 0.001], osteoid surface (Osteoid Surface/Bone Surface, OS/BS) [0.772/2.17 (median/IQR, OS/BS; %), P < 0.001] and osteoclasts number (Osteoclasts per millimetre bone surface, Ocl/mmBS; mm2) [0.026/0.123 (median/IQR, Ocl/mmBS; mm2), P < 0.001] were decreased; trabecular number (Tb.N) was lower [1.63/0.63 (median/IQR, Tb.N; 1/mm-1), P = 0.012] and trabecular separation (Tb.Sp) [0.626/0.24 (median/IQR, Tb.Sp; µm), P = 0.038] was higher in irradiated mandibular bone. With higher Dmax, trabecular number increases (Spearman's correlation R = 0.470, P = 0.018) and trabecular separation decreases (Spearman's correlation R = -0.526, P = 0.007). Bone mineral density (BMD, milligrams hydroxyappetite per cubic centimetre, mgHA/cm3) [1016/99 (median/IQR, BMD; mgHA/cm3), P = 0.03] and trabecular separation [0.739/0.21 (median/IQR, Tb.Sp; µm), P = 0.005] are higher whereas connectivity density (Conn Dens) [3.94/6.71 (median/IQR, Conn Dens), P = 0.047] and trabecular number [1.48/0.44 (median/IQR, Tb.N; 1/mm-1), P = 0.002] are lower in Dmax ≤50 Gy compared to controls. CONCLUSIONS: Radiotherapy dramatically impairs bone turnover in the mandible. Deterioration in microarchitecture only affects bone irradiated with a Dmax of <50 Gy. The 50 Gy value seems to be a critical threshold to where the effects of the radiation is more detrimental.

[A phd completed. The effect of radiotherapy on oral mucosa cell morphology.] / Serie: Hora est. Het effect van radiotherapie op de morfologie van de orale mucosa.

The treatment of oral cancer usually consists of surgical removal of the tumour, possibly followed by radiotherapy. The purpose of this dissertation research was to investigate the effects of radiotherapy on the oral tissues, in particular the superficially positioned epithelial cells in the oral mucosa. Earlier studies with electron microscopy revealed that unradiated oral mucosa cells, when observed at high magnification, contain microplicae (ridges or folds). Together with various saliva components, these microplicae form a protective layer that offers defence against, for instance, microorganisms. Radiotherapy damages these microplicae and may even destroy them altogether. Studies have shown that this effect of radiation can be observed in animals as well as in humans. As the radiation dose increased (50 Gy or more) the destruction of the microplicae was more severe. With a dose of 60 Gy or more the microplicae completely disappeared. This process may play an important role in the occurrence of osteoradionecrosis in the jaw and failure of dental implants placed after radiotherapy.

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.

Dental caries and mutans streptococci in relation to plasma ascorbic acid.

Ascorbic acid (AA) affects in vitro growth of bacteria and may also act in vivo to decrease caries activity. The aim of this study was to evaluate the possible association of AA level in plasma with number of caries lesions, relative numbers of some species of oral cariogenic flora, and rate of salivary secretion. The caries status and some bacteriologic variables of dentulous adult subjects with a low level of AA in the plasma (< or = 25 mumol/l; n = 75) were compared with those of controls (plasma level > or = 50 mumol/l; n = 75) matched for age, sex, and number of teeth. For each subject, site-specific recordings of the presence or absence of plaque, dental caries, fillings, and erosions were recorded clinically by the same dentist in a double-blind system. The amounts of visible plaque and numbers of decayed tooth surfaces were significantly higher in the low AA group than in the controls. No between-group differences were found in the number of fillings and the amount of oral bacterial growth. The frequencies of consumption of vegetables, berries, and other fruit were significantly lower in the low AA group than in the controls.

Periodontal health related to plasma ascorbic acid.

The exact relationship between plaque-induced periodontal diseases and vitamin C deficiency is not known. The aim of this study was to evaluate the possible effect of ascorbic acid (AA) on the severity of periodontal diseases. The periodontal condition of 75 dentulous subjects with a low level of AA in the plasma (< or = 25 mumol/l) was compared with that of 75 control subjects (plasma level > or = 50 mumol/l) matched for age, sex and number of teeth. The subjects were asked to list foods containing AA in their diet, and intake of AA in milligrams per day was calculated. The daily diet of the study subjects contained on average 52 mg +/- 24.9 (SD) of AA, and that of the controls 77 mg +/- 43.2 (SD). For each individual, site-specific recordings for the presence or absence of plaque and supra- and subgingival calculus, filling overhangs, gingival bleeding after probing, probing pocket depth, and gingival recession were made clinically in a double blind examination carried out by one dentist. Five per cent of the subjects in the study group (low plasma level of AA) and 18 per cent of the controls had healthy periodontal tissues. The proportion of sites in which bleeding after probing and a probing pocket depth of 4 mm or over were observed was significantly higher in the study group than in the controls. Sixty per cent of the subjects in the study group and 37 per cent of the controls had pathological pockets of 4 mm or over.(ABSTRACT TRUNCATED AT 250 WORDS)