Nw Savage

The pathogenesis of oral lichen planus

Both antigen-specific and non-specific mechanisms may be involved in the pathogenesis of oral lichen planus (OLP). Antigen-specific mechanisms in OLP include antigen presentation by basal keratinocytes and antigen-specific keratinocyte killing by CD8(+) cytotoxic T-cells. Non-specific mechanisms include mast cell degranulation and matrix metalloproteinase (MMP) activation in OLP lesions. These mechanisms may combine to cause T-cell accumulation in the superficial lamina propria, basement membrane disruption, intra-epithelial T-cell migration, and keratinocyte apoptosis in OLP. OLP chronicity may be due, in part, to deficient antigen-specific TGF-beta1-mediated immunosuppression. The normal oral mucosa may be an immune privileged site (similar to the eye, testis, and placenta), and breakdown of immune privilege could result in OLP and possibly other autoimmune oral mucosal diseases. Recent findings in mucocutaneous graft-versus-host disease, a clinical and histological correlate of lichen planus, suggest the involvement of TNF-alpha, CD40, Fas, MMPs, and mast cell degranulation in disease pathogenesis. Potential roles for oral Langerhans cells and the regional lymphatics in OLP lesion formation and chronicity are discussed. Carcinogenesis in OLP may be regulated by the integrated signal from various tumor inhibitors (TGF-beta 1, TNF-alpha, IFN-gamma, IL-12) and promoters (MIF, MMP-9). We present our recent data implicating antigen-specific and non-specific mechanisms in the pathogenesis of OLP and propose a unifying hypothesis suggesting that both may be involved in lesion development. The initial event in OLP lesion formation and the factors that determine OLP susceptibility are unknown.

Distribution of interleukin-2, -4, -10, tumour necrosis factor-α and transforming growth factor-β mRNAs in oral lichen planus

In the present study. MRNA for the cytokines interleukin-2 (IL-2), IL-4, IL-10 tumour necrosis factor-α (TNF-α) and transforming growth factor β-1 (TGF-β-1) were investigated in oral lichen planus (OLP) lesions using in situ hybridization with 35S-labelled oligonucleotide probes on frozen tissue sections. In addition, the expression of interferon-γ (IFN-γ), IL-10 and IL-4 mRNAs was analysed in cultured lesional T lymphocytes from oral lichen planus by polymerase chain reaction. Cells expressing mRNA for IL-2, IL-4, IL-10, TNF-α and TGF-β1 were found in all the biopsies studied. Approximately 1–2% of the total number of infiltrating cells in the lesions were positive for each of the different cytokine mRNAs. Most biopsies contained basement membrane-oriented, mRNA-positive cells. In the cultured T-cell lines, message for IFN-γ was detected in all the patients, IL-10 in all but one, and IL-4 in just one of the seven patients investigated. The results suggest that mRNA for both pro- and anti-inflammatory cytokines, i.e., mixed T-helper 1 (TH1) and TH2 cytokine profiles, are generated simultaneously by a limited number of cells in chronic lesions of OLP.

T-lymphocyte subset changes in recurrent aphthous stomatitis

Immunocytochemical techniques using monoclonal antibodies directed against T-lymphocyte surface antigens (OKT3, OKT4, and OKT8) were used to investigate changes in the T-cell subpopulations throughout the natural time course of recurrent aphthous stomatitis (RAS). All lesions contained large numbers of OKT3-positive T cells. Preulcerative lesions were characterized by many OKT4-positive inducer/helper cells and few OKT8-positive suppressor/cytotoxic cells (T4:T8 approximately equal to 2:1). The ulcerative lesion contained large numbers of OKT8-positive suppressor/cytotoxic cells and only a very small number of OKT4-positive cells (T4:T8 approximately equal to 1:10). The healing lesion once again became dominated by OKT4-positive cells, with only a small number of OKT8 positive cells present (T4:T8 approximately equal to 10:1). The results support the role of lymphocytotoxicity in the establishment of the RAS lesion and may suggest a local immunoregulatory imbalance. NK cells, Leu-7 positive, were also identified in the preulcerative lesions and very early ulcerative lesions.

Matrix metalloproteinases and their inhibitors in oral lichen planus

Background: Oral lichen planus (OLP) is characterized by a sub‐epithelial lymphocytic infiltrate, basement membrane (BM) disruption, intra‐epithelial T‐cell migration and apoptosis of basal keratinocytes. BM damage and T‐cell migration in OLP may be mediated by matrix metalloproteinases (MMPs).

Burning mouth syndrome and psychological disorders

Burning mouth syndrome (BMS) is an oral dysaesthesia that causes chronic orofacial pain in the absence of a detectable organic cause. The aetiology of BMS is complex and multifactorial, and has been associated in the literature with menopause, trigger events and even genetic polymorphisms. Other studies have found evidence for mechanisms such as central and peripheral nervous system changes, with clinical and laboratory investigations supporting a neuropathologic cause. These physiological explanations notwithstanding, there is still much evidence that BMS aetiology has at least some psychological elements. Somatoform pain disorder has been suggested as a mechanism and factors such as personality, stress, anxiety, depression and other psychological, psychosocial and even psychiatric disorders play a demonstrable role in BMS aetiology and symptomatology. In order to treat BMS patients, both physiological and psychological factors must be managed, but patient acceptance of possible components of psychological disease basis is a major hurdle. Clinical signs of patient stress, anxiety or depression are a useful reinforcement of clinical discussions. The current paper proposes a number of clinical signs that may be useful for both clinical assessment and subsequent patient discussions by providing visible supportive evidence of the diagnosis.

Management and recurrence of keratocystic odontogenic tumor: a systematic review

OBJECTIVES The objective of this study was to evaluate the most up-to-date treatment modalities and respective recurrence rates for keratocystic odontogenic tumor (KCOT). STUDY DESIGN A systematic review of the literature from 1999 to 2010 was undertaken examining treatment and recurrence rates for KCOT. Four inclusion criteria were defined for articles to then be analyzed against 8 standards. RESULTS Of the 2736 published articles, 8 met the inclusion criteria. When merging the data, enucleation and enucleation with adjunctive measures (other than Carnoys solution) had recurrence rates of 25.6% and 30.3%, respectively. Marsupialization with adjunctive measures produced a recurrence rate of 15.8%, whereas enucleation with Carnoys solution presented a recurrence rate of 7.9%. Only one resection case had recurrence (6.3%). CONCLUSIONS The enucleation technique with the use of adjunctive procedures (other than Carnoys solution) provides a higher recurrence rate than any other treatment modality.

Disinfection of dental stone casts: Antimicrobial effects and physical property alterations

OBJECTIVES The purpose of this study was to evaluate the effectiveness of disinfecting solutions incorporated into dental stone casts against a standard and representative group of microorganisms and to note changes in the physical properties of the casts. METHODS Irreversible hydrocolloid impressions were contaminated individually with Escherichia coli, Staphylococcus aureus, Enterobacter cloacae, Pseudomonas aeruginosa, Klebsiella pneumoniae, Actinobacter calcoaceticus, Bacillus subtilis, Mycobacterium phlei and Candida albicans. Four readily available disinfecting solutions (glutaraldehyde, povidone-iodine, chlorhexidine and sodium hypochlorite) were added to the die stone mix used to pour up the impressions. The set cast surfaces were swabbed at 1 h and 24 h, the samples plated on agar and incubated at 37 degrees C for 24 h and 3 d for M. phlei. Subsequently, colony forming units were counted. The physical properties assessed were setting time, setting expansion, compressive strength, detail reproduction and delayed expansion of the stone. RESULTS Only glutaraldehyde and povidone-iodine killed all contaminating microorganisms within 1 h, while the 1:5 dilution of sodium hypochlorite solution was equally effective after 24 h. Two percent glutaraldehyde was the most effective disinfectant with the least adverse effects on the physical properties of the set cast. Although povidone-iodine caused a decrease in the compressive strength of the set cast, it can be considered to be a sound alternative. SIGNIFICANCE This study supports the concept of incorporating disinfectants into model stone as a standard operating procedure for impressions of unknown history and, most sensibly, all dental impressions.

Disease mechanisms in oral lichen planus. A possible role for autoimmunity.

Current evidence for the involvement of cell‐mediated immunological mechanisms in the pathogenesis of oral lichen planus is reviewed. Both a spatial and temporal relationship between cytotoxic T Lymphocytes and epithelial damage have been reported. Although keratinocytes appear to be the target for destruction in oral lichen planus, their role in antigen presentation is unclear. We propose that in oral lichen planus patients, diverse exogenous agents such as drugs, trauma and infection, stimulate the expression of a common self molecule by oral mucosal keratinocytes. An autoimmune reaction by cytotoxic T lymphocytes to these activated keratinocytes may result in the tissue destruction which is characteristic of oral lichen planus.

In Situ Hybridization Evidence for a Paracrine/Autocrine Role for Insulin-Like Growth Factor-I in Tooth Development

Insulin-like growth factor-I(IGF-I) has both metabolic and growth-promoting activities in many cell and tissue types. Although IGF-I is present in serum, it is also thought to have important autocrine and paracrine functions. Immunohistochemistry for IGF-I and its receptor have shown that IGF-I is synthesised locally by the tooth forming cells which exhibit both the IGF-I and the growth hormone receptors. This concept required to be tested by in situ hybridization. Using a digoxigenin-labelled synthetic oligodeoxyribonucleotide probe for IGF-I, we investigated the distribution of IGF-I mRNA in the continuously erupting rat incisor by in situ hybridization. The distribution and intensity of the hybridization signal varied with the developmental stage of the rat incisor. The cells of the apical loop expressed a positive hybridization signal, but the earliest polarised odontoblasts and pre-ameloblasts did not show any positive signal. The onset of enamel secretion was accompanied by a strong hybridization signal in the secretory ameloblasts as well as the odontoblasts. Maturation ameloblasts also demonstrated IGF-I message in their cytoplasm as well as their nuclei. The cells of the pulp and the dental follicle were consistently negative. However, in the adjacent alveolar bone, the signal was high in the osteoblasts and osteoclasts. These findings support the notion of paracrine or autocrine function for IGF-I in tooth development.

Oral Mucosal Langerhans Cells Express DR and DQ Antigens

The expression of the Class II antigens HLA-DR and HLA-DQ in human oral mucosa was examined in health and in the presence of inflammation. DQ antigens were detected on dendritic intra-epithelial cells which expressed the Langerhans cells (LC) phenotype T6+, DR+. In healthy gingiva, DR and DQ were co-expressed on Langerhans cells, whereas in an experimental gingivitis (day 8), more LC expressed DR than DQ. Absolute LC numbers were increased in inflammation. Traumatic ulceration of the buccal mucosa resulted in a decrease in the density of T6-, DR-, and DQ-positive cells. Re-population of migrating and regenerated epithelium was complete 10 days after ulcer induction. Disparity between DR and DQ expression was seen in both normal buccal mucosa and throughout the ulcer healing period. These results are in agreement with the reported sequence of Class II antigen expression on lymphoid cells.