Effect of melatonin on the gastric antioxidant defence in experimental burn trauma.

Severe burn trauma triggers oxidative gastric mucosal injury. The purpose of this study was to investigate the antioxidant defence mechanisms and protective effect of melatonin in the gastric mucosa after burn injury. In order to investigate the mechanisms involved in the gastric antioxidant defence in a rat burn model, quantitative real-time PCR and immunohistochemistry techniques were applied. An analysis of glutathione peroxidase 4 (GPx4), glutathione reductase (GR), and catalase (Cat) gene expression was performed along with the evaluation of the gastric Cu/Zn superoxide dismutase (Cu/Zn SOD) activity. Melatonin was applied immediately and 12 h after 30% of total body surface area burns. The burn injury significantly increased the Gpx4 mRNA (P < 0.000 1) and Gsr mRNA (P < 0.000 1) expression. It also had a slight positive effect on the Cat mRNA expression and Cu/Zn SOD activity. Melatonin, in turn, markedly augmented the burn-induced Cu/Zn SOD (P < 0.000 1) activity, reversed the Gpx4 mRNA (P < 0.000 1) and Gsr mRNA (P < 0.000 1) expression, and inhibited the Cat mRNA level. In conclusion, the present study suggests that a burn injury adaptively increases the Cu/Zn SOD activity and enhances the Gpx4 and Gsr gene expression in the gastric mucosa. Melatonin effectively modulates the expression of the cellular antioxidant enzymes, and improves the antioxidant defence by augmenting the Cu/Zn SOD activity.

Radiation-induced low grade fibromyxoid sarcoma of the larynx: a case report and literature review.

Low grade fibromyxoid sarcoma (LGFMS) is an uncommon variant of fibrosarcoma with high risk of local recurrence, immense metastatic potential and frequently protracted period between tumour presentation and metastasis. This unusual malignancy rarely affects the region of the head and neck which makes cases of laryngeal LGFMS extremely infrequent. To date, LGFMS of the larynx has been scatteredly mentioned in the literature. Neither incidence nor causes and risk factors for laryngeal LGFMS have been clarified so far. To the authors' knowledge, this is the first case report that discusses the clinical course, imaging diagnosis, histopathological evaluation and surgical approach to radiation-induced laryngeal LGFMS.We present a case of a 70-year-old man who developed a LGFMS after previous radiotherapy (RT) for squamous cell carcinoma (SCC) of the larynx. The latency period between the time of radiation exposure and the diagnosis of LGFMS was twenty-seven months. After re-confirming the diagnosis with second biopsy and extensive imaging evaluation the patient was subjected to an open partial resection of the larynx. Owing to the rarity of the tumour, there is no established protocol with follow-up recommendations.This case highlights the importance of considering the RT history of the patient in order to monitor radiotherapy-related complications, including the occurrence of LGFMS.

Molecular Mechanisms of Melatonin Protection from Gastric Mucosal Apoptotic Injury in Experimental Burns.

Melatonin, a basic secretory pineal gland product, is a nontoxic, multifunctional molecule. It has antioxidant and anti-apoptotic activities and protects tissues from injury. The objective of the present study was to determine the molecular mechanism of melatonin anti-apoptotic effect on gastric injury in a rat burn model. We hypothesized that melatonin gastric protection may be related to the activation of transcription erythroid 2-related factor 2 (Nrf2). Using a 30% total body surface area (TBSA) rat burn model, melatonin (10 mg/kg, i.p.) was injected immediately and 12 h after thermal skin injury. Via light immunohistochemistry, we determined the tissue level of 4-hydroxy-2-nonenal (4-HNE) as a marker of lipid peroxidation, Bcl-2 and Bax as apoptosis-related proteins, and Nrf2. Results are presented as medians (interquartile range (IQR)). Thermal trauma in burned animals, compared with the controls, increased the expression of pro-apoptotic Bax protein (1.37 (0.94-1.47)), decreased anti-apoptotic Bcl-2 protein (1.16 (1.06-1.23), p < 0.001) in epithelial cells, and elevated Bax/Bcl-2 ratios (p < 0.05). Tissue 4-HNE and Nrf2 levels were increased following severe burns (1.55 (0.98-1.61) and 1.16 (1.01-1.25), p < 0.05, respectively). Melatonin significantly decreased 4-HNE (0.87 (0.74-0.96), p < 0.01) and upregulated Nrf2 (1.55 (1.52-1.65), p < 0.001) levels. It also augmented Bax (1.68 (1.5-1.8), p < 0.001) and Bcl-2 expressions (1.96 (1.89-2.01), p < 0.0001), but reduced Bax/Bcl-2 ratios (p < 0.05). Our results suggest that experimental thermal trauma induces oxidative gastric mucosal injury. Melatonin manifests a gastroprotective effect through Nrf2 activation, lipid peroxidation attenuation, and Bax/Bcl-2 ratio modification as well.