bromochloroacetic-acid and Mucositis

Radiation-induced oral mucositis is one of the most common adverse events in radiation therapy for head and neck cancers, but treatments for oral mucositis are limited to palliative and supportive care. New approaches are required to prevent radiation-induced mucositis and to improve treatments. The Keap1-Nrf2 system regulates cytoprotection against oxidative and electrophilic stresses. Nrf2 also regulates keratin layer thickness in mouse tongues. Therefore, we hypothesized that Nrf2 may protect the tongue epithelium against radiation-induced mucositis via elimination of reactive oxygen species and induction of keratin layer thickening. To test this hypothesis, we prepared a system for γ-ray exposure of restricted areas and irradiated the tongues of model mice with Nrf2 and Keap1 loss-of-function. We discovered that loss of Nrf2 expression indeed sensitized the tongue epithelium to radiation-induced ulcer formation with inflammation. Constitutive Nrf2 activation by genetic Keap1 knockdown alleviated radiation-induced DNA damage by increasing antioxidation. In agreement with the genetic Nrf2 activation model, the Nrf2 inducer CDDO-Im prevented irradiation damage to the tongue epithelium. These results demonstrate that Nrf2 activation has the potential to prevent the development of radiation-induced mucositis and that Nrf2 inducers are an important therapeutic drug for protection of the upper aerodigestive tract from radiation-induced mucositis.

Topics: Animals; Antioxidants; Cytoskeletal Proteins; Kelch-Like ECH-Associated Protein 1; Keratins; Mice; Mucositis; NF-E2-Related Factor 2; Oleanolic Acid; Radiation Injuries; Stomatitis

The objective was to assess the inter-rater agreement in the diagnosis of mucositis and peri-implantitis.. Adult patients with ≥ 1 dental implant were eligible. Three operators examined the patients. One examiner allocated the patients to three groups of nine as follows: nine implants with peri-implantitis, nine implants with mucositis, and 9 implants with healthy mucosa. Each examiner recorded on all 27 patients (one implant per patient) recessions, probing depth, bleeding on probing, suppuration, keratinized tissue depth and bone loss, leading to a final diagnosis of mucositis, peri-implantitis or healthy mucosa. Examiners were independent and blinded to each other.. Fleiss k-statistic with quadratic weight in the diagnosis of peri-implantitis and mucositis was 0.66 [CI95%: 0.45-0.87]. A complete agreement was obtained only in 14 cases (52%). Fleiss k-statistics in bleeding on probing and bone loss were respectively 0.31 [CI95%: 0.20-0.41] and 0.70 [CI95%: 0.45-0.94]. Intra-class correlation coefficients for recession, probing depth and keratinized tissue depth were respectively 0.69 [CI95%: 0.62-0.75], 0.54 [CI95%: 0.44-0.63] and 0.56 [CI95%: 0.27-0.77].. The inter-rater agreement in the diagnosis of peri-implant disease was qualified as merely good. This could also be due in part to the unclear definition of peri-implantitis and mucositis.

Topics: Adult; Aged; Alveolar Bone Loss; Consensus; Dental Implants; Female; Gingiva; Gingival Recession; Humans; Keratins; Male; Middle Aged; Mucositis; Observer Variation; Peri-Implantitis; Periodontal Index; Periodontal Pocket; Single-Blind Method; Suppuration

The aim of this work was to study cytokeratin (Ck) expression in initial radiation-induced oral mucositis.. Eleven cases of initial radiomucositis of the buccal mucosa and 9 normal specimens were immunostained for Ck 1, 5, 6, 7, 8, 10, 14, 16, 18, and 19 by immunoperoxidase method.. Expression of Ck 1, 6, 10, and 16 was stronger in mucositis than in normal mucosa. Ck 7, 8, and 18 were negative for both control and study groups. Ck 5, 13, and 14 were positive for both groups, nevertheless suprabasal staining for Ck 14 was more evident in mucositis than in the control group. Sporadic staining for Ck 19 was observed in 1 case of mucositis and in 2 controls.. Increased Ck expression can be associated with the reactive proliferation of the epithelium and increasing resistance of the oral mucosa during the initial phases of radiotherapy.

Topics: Adult; Cranial Irradiation; Female; Humans; Immunoenzyme Techniques; Keratin-1; Keratin-10; Keratin-14; Keratin-16; Keratin-6; Keratins; Male; Middle Aged; Mucositis; Radiation Injuries; Radiotherapy Dosage; Stomatitis