Khat alters the phenotype of in vitro-reconstructed human oral mucosa.

Khat-chewing has been associated with oral lesions including oral cancer, but the mechanisms leading to their development are not known. We hypothesized that khat interferes with the physiological processes of the oral mucosa, such as cell proliferation and differentiation, and aimed at investigating the effects of khat exposure on in vitro-reconstructed human normal buccal mucosa. Khat decreased cell proliferation, epithelial thickness, and cytokeratin 13 expression, while inducing premature expression of p21(Waf1/Cip1), transglutaminases, involucrin, and filaggrin. This suggests that khat is able to induce abnormal differentiation of the buccal epithelium. Khat-induced alterations were accompanied by increased levels of p38 and were reversed by p38 inhibition, pointing to p38 as the key player in this process. The morphological changes described herein mirror the in vivo changes previously described in khat users, and demonstrate for the first time that khat induces pathological alterations in human buccal mucosa, providing evidence that raises concerns about the effects of khat use on oral health.

Radiotherapy reduces sialorrhea in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder. Sialorrhea is a frequent problem in ALS patients with bulbar symptoms, because of progressive weakness of oral, lingual and pharyngeal muscles. This prospective study aimed to investigate the putative effect of palliative single-dose radiotherapy on problematic sialorrhea in patients with ALS. Twenty patients with ALS and problematic drooling were included; 14 were given radiotherapy with a single fraction of 7.5 Grey (Gy). Five patients were treated with botulinum toxin A (BTX-A) injections (20 U) into the parotid glands; two of these were later given radiotherapy. Symptom assessment, clinical examination and measurements of salivary flow (ml/min) were performed before and after treatment (1-2 weeks, 3 months). Salivary secretion was significantly reduced after radiation treatment, with a mean reduction of 60% (1 week) and 51% (2 weeks). Three months post-treatment, 21% reduction of the salivary secretion was observed compared with salivation before treatment. Mean salivary flow was not reduced after BTX-A treatment in five patients. No serious side-effects were observed with either of the two treatment modalities. Single-dose radiotherapy (7.5 Gy) significantly reduces sialorrhea and is an effective and safe palliative treatment in patients with ALS.

Altered CD40 and E-cadherin expression--putative role in oral lichen planus.

BACKGROUND: Oral lichen planus (OLP) is characterized among other features by apoptosis of basal keratinocytes. To identify potential regulatory mechanisms associated with basal cell apoptosis in OLP, we investigated the expression of CD40, CD40 ligand (CD40L), CD44 and epithelial (E)-cadherin. METHODS: Biopsies from 22 patients with OLP were investigated by immunohistochemistry for detection of CD40, CD40L, E-cadherin, CD44, Laminin-5 and Collagen IV, double-labelling for CD40 and CD3, and in situ mRNA hybridization for CD40 and CD40L. RESULTS: In actively diseased areas of OLP lesions, basal keratinocytes did not express CD40 and were focally E-cadherin-negative, in contrast to non-diseased areas and normal oral mucosa. Demonstration of intraepithelial T cells expressing CD40 and CD40L, indicates a potential role in inflammatory cell responses involved in the disease process of OLP. CONCLUSION: T cells may orchestrate inflammatory cell responses in OLP via CD40-CD40L interactions. As basal keratinocytes downregulate CD40, they may escape CD40-CD40L-induced apoptosis in OLP. On the other hand, loss of E-cadherin expression may contribute to epithelial basal cell destruction and T-cell migration into the epithelial compartment in OLP.

Apoptosis in oral lichen planus.

Apoptotic cell death may be a contributory cause of basal cell destruction in oral lichen planus (OLP). Therefore. the purpose of this study was to investigate the rate of apoptosis in OLP and the expression of two proteins (FasR and FasL) regulating this process. Biopsies from 18 patients with histologically diagnosed OLP were investigated, with comparison to normal oral mucosa of healthy persons. For visualisation of DNA fragmentation, the TUNEL method was used. In order to characterise the infiltrating cell population (CD3. CD4, CD8) and expression of FasR and FasL, we used an immunohistochemical technique. The results showed that T cells dominated in the subepithelial cell infiltrate. Within the epithelium the apoptotic cells were confined to the basal cell layer, and more apoptotic cells were seen in areas with basal cell degeneration and atrophic epithelium. There was a prominent expression of FasR/FasL in OLP. with a rather uniform distribution throughout the inflammatory cell infiltrate. In the epithelium, the FasR/FasL expression was more abundant in the basal cell area compared to the suprabasal cell layer. In conclusion, apoptosis within the epithelium is significantly increased in situ in OLP compared to normal oral mucosa, and seems to be related to the epithelial thickness.