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.

Anticholinergic Burden and Dry Mouth in Middle-Aged People.

INTRODUCTION: Anticholinergic burden refers to the cumulative effect of taking 1 or more drugs with anticholinergic properties. At the moment, little is known about the association between the anticholinergic burden and dry mouth. OBJECTIVES: The objective of this article was to study, whether an anticholinergic burden is associated with dry mouth among middle-aged people. METHODS: The study population included 1,345 people aged 46 y from the Northern Finland Birth Cohort 1966 (NFBC1966) study, who took part in a clinical medical and dental examination during 2012-2013. Medication data comprised both self-reported drug use and information obtained from the national register. Anticholinergic burden was measured using 10 different anticholinergic scales. Dry mouth was defined on the basis of having either a subjective feeling of dry mouth (xerostomia) or objectively measured low unstimulated or stimulated whole salivary flow rates (hyposalivation). Poisson regression models with robust error variance were used to estimate relative risk (RR). Regression models were adjusted for sex, smoking, diabetes, rheumatoid diseases, depressive symptoms, anxiety, total number of drugs, and antihypertensive drugs. RESULTS: Approximately 14% of the participants reported having xerostomia and about 2% had hyposalivation. The RRs of different anticholinergic scales for xerostomia varied from 1.05 to 1.68. The scales' RRs were between 0.89 and 2.03 for low unstimulated whole salivary flow (<0.1 mL/min) and between 0.59 and 1.80 for low stimulated whole salivary flow (<0.7 mL/min). Seven of 10 studied anticholinergic scales associated statistically significantly with dry mouth, either with xerostomia or hyposalivation. CONCLUSION: Most of the anticholinergic scales were associated with dry mouth, either with xerostomia or hyposalivation. There was considerable variation in the strength of the associations between anticholinergic scales and dry mouth. KNOWLEDGE TRANSFER STATEMENT: The findings of this study suggest that dentists should take notice of the use of drugs with anticholinergic properties and their harmful effects among middle-aged people. Dentists should provide these patients with necessary guidance on how to cope with dry mouth and give them prophylactic measures against oral diseases associated with dry mouth.

[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.

Osseointegration of dental implants in bone irradiated with 40, 50 or 60 gy doses. An experimental study with beagle dogs.

Construction of different kinds of prostheses on irradiated bone tissues after tumour surgery is a complicated part of modern implantology. In irradiated regions of the jaws where the bone layers are thin and the blood supply also is minimal, knowledge of the impact of each dose of radiation is very important. The aim of this study was to compare the bone response around titanium implants loaded with fixed bridges in dog mandibles irradiated with total doses of 40, 50 or 60 Gy. The results suggest that after irradiation with 40-50 Gy, when the dose is fractioned in order to achieve higher tolerance of the tissues compared with single dose irradiation, titanium implants may become osseointegrated in the mandibles. For high success rates, however, careful planning of radiotherapy and selection of implantation site with an adequate blood supply are essential.

Nickel allergy in adolescents in relation to orthodontic treatment and piercing of ears.

The aim of this study was to investigate the frequency of nickel hypersensitivity in adolescents in relation to sex, onset, duration and type of orthodontic treatment, and the age at which ears were pierced. The subjects were 700 Finnish adolescents, from 14 to 18 years of age, of which 476 (68%) had a history of orthodontic treatment with metallic appliances. The study consisted of patch-testing for a nickel allergy and a patient history obtained by a questionnaire and from patient record. The frequency of nickel sensitization in the whole group was 19%. Nickel allergy was significantly more often found in girls (30%) than in boys (3%) and in subjects with pierced ears (31%) than in those with no piercing of ears (2%). Orthodontic treatment did not seem to affect the prevalence of nickel sensitization. None of the girls who were treated with fixed orthodontic appliances before ear piercing showed hypersensitivity to nickel, whereas 35% of the girls who had experienced ear piercing before the onset of orthodontic treatment were sensitized to nickel. The results suggest that orthodontic treatment does not seem to increase the risk for nickel hypersensitivity. Rather, the data suggests that treatment with nickel-containing metallic orthodontic appliances before sensitization to nickel (ear piercing) may have reduced the frequency of nickel hypersensitivity.

Allergic patch test reactions to palladium chloride in schoolchildren.

A study of the prevalence of allergic patch test reactions to palladium chloride compared to nickel sulfate was performed in a group of Finnish schoolchildren. All adolescents 14-18 years of age in a Finnish town with 40,000 inhabitants, who had received orthodontic treatment with metallic appliances at a municipal dental clinic, were included in the study. The selection of patients was based on patient records. A non-treatment control group was randomly selected from the same age groups of the town population. A total of 700 subjects (77% of those invited), 417 (60%) girls and 283 (40%) boys, participated. The majority (91%) of the girls had pierced ears. Orthodontic treatment was equally common (67-70%) in the boys and the girls. The girls had a much higher frequency of allergic patch test reactions to both nickel sulfate and palladium chloride. Of the 700 adolescents tested, 48 (7%) had an allergic patch test reaction to palladium chloride. Of the 417 girls, 44 (11%) were palladium-chloride-positive, whereas only 4 of the 283 boys tested (1%) had an allergic patch test reaction to palladium chloride. 3 patients reacted to palladium chloride only, whereas all other patients with allergic patch test reactions to palladium chloride also had an allergic patch test reaction to nickel sulfate. The results support the concept of cross-reactivity between nickel sulfate and palladium chloride. The clinical significance of the allergic patch test reactions caused by palladium chloride remains unclear.

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.

A new application of a screw-plate for prosthetic reconstruction after bilateral total maxillectomy.

Satisfactory functional and aesthetic rehabilitation of a patient after total bilateral maxillectomy is a great challenge to the surgeon and prosthodontist. A particular problem is support and retention of the obturator. In the case described, the problem was solved by attaching the prosthesis with finger clasps to a classic AO-reconstruction plate anchored rigidly with screws to both zygomata. The results in terms of mastication, swallowing, phonation and aesthetics were satisfactory for more than 2 years, when the patient died from brain metastasis and pneumonia. The technique seems promising and merits further study using titanium screws and plates.

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)

Expression of intermediate filaments in human tongue mucosa.

The specific inflammatory lesions of the human tongue, namely fissured tongue and geographic tongue, have been found to differ clinically and histologically from each other and from healthy appearing tongue (control). In this study we describe expression of cytokeratin, vimentin and desmin intermediate filaments in these tongue forms. The most important findings were seen in fissured tongue; strong positive staining of cytokeratin proteins indicate the incomplete keratinization of the epithelium, vimentin staining was irregular indicating subepithelial edema and desmin expression showed the destruction of the uppermost muscle cells. The corresponding changes of geographic tongue were similar but slight when compared with those of fissured tongue. Different immunohistochemical methods can supplement the information obtained from tongue biopsies by conventional methods and lead to a better understanding of the morphology of the tongue mucosa.

Oral mucosal changes related to plasma ascorbic acid levels.

The role of vitamin C in maintaining mucosal health is poorly documented. The purpose of this study was to examine the presence of oral mucosal lesions in subjects with low ascorbic acid (AA) levels in plasma. AA plasma levels of 843 working elderly people in six rural villages in Eastern Finland were determined. All subjects with low plasma AA levels (< or = 25 mumol/l) (n = 106) formed the study group. Controls with normal AA levels (> or = 50 mumol/l) (n = 103) were drawn from the same population. They were matched for age, sex and number of teeth. Oral mucosal lesions in all subjects were recorded clinically using a double-blind method in all subjects. Petechias, leukoplakia and lichenoid lesions were the commonest lesions of the oral mucosa. Only in leukoplakia there was a statistically significant difference between the groups (p < 0.01). Smokers had more leukoplakia than non-smokers. The prevalence of leukoplakia was higher when smoking was combined with AA deficiency.

Osseo-integration of dental implants in radiated mandibles: an experimental study with beagle dogs.

This investigation was planned to detect the ability of radiated bone to integrate with dental implants and to study the load-bearing capacity of these implants. In five beagle dogs, the premolars were extracted, after which one side of the mandible was radiated with 40 Gy. Three months later, two hollow-cylinder implants were placed on each side of the mandible. After a three-month period of osseo-integration, bridges were constructed on the implants, and they were loaded for six months. Both clinical and x-ray examinations showed that all implants had integrated well and bore load without change in their host sites for a six-month period, at which time the dogs were killed.