Memantine, a noncompetitive antagonist of the N-methyl-d-aspartate (NMDA) receptor, suppresses the release of excessive levels of glutamate that may induce neuronal excitation. Here we investigated the effects of memantine on salicylate-induced tinnitus model. The expressions of the activity-regulated cytoskeleton-associated protein (ARC) and tumor necrosis factor-alpha (TNF α)genes; as well as the NMDA receptor subunit 2B (NR2B) gene and protein, were examined in the SH-SY5Y cells and the animal model. We also used gap-prepulse inhibition of the acoustic startle reflex (GPIAS) and noise burst prepulse inhibition of acoustic startle, and the auditory brainstem level (electrophysiological recordings of auditory brainstem responses, ABR) and NR2B expression level in the auditory cortex to evaluate whether memantine could reduce salicylate-mediated behavioral disturbances. NR2B was significantly upregulated in salicylate-treated cells, but downregulated after memantine treatment. Similarly, expression of the inflammatory cytokine genes TNFα and immediate-early gene ARC was significantly increased in the salicylate-treated cells, and decreased when the cells were treated with memantine. These results were confirmed by NR2B immunocytochemistry. GPIAS was attenuated to a significantly lesser extent in rats treated with a combination of salicylate and memantine than in those treated with salicylate only. The mean ABR threshold in both groups was not significant different before and 1 day after the end of treatment. Additionally, NR2B protein expression in the auditory cortex was markedly increased in the salicylate-treated group, whereas it was reduced in the memantine-treated group. These results indicate that memantine is useful for the treatment of salicylate-induced tinnitus.
Acoustics ; Animals ; Auditory Cortex ; Brain Stem ; Evoked Potentials, Auditory, Brain Stem ; Genes, Immediate-Early ; Glutamic Acid ; Immunohistochemistry ; Integrin alpha2 ; Memantine ; Models, Animal ; N-Methylaspartate ; Neurons ; Noise ; Prepulse Inhibition ; Rats ; Reflex, Startle ; Tinnitus ; Tumor Necrosis Factor-alpha

BACKGROUND: Esophageal perforation is an emergency that requires early diagnosis and effective treatment. A delay in diagnosis and treatment significantly increases morbidity and mortality. MATERIAL AND METHOD: Thirty-seven patients with esophageal perforation were surgically treated at our institutions between January 1990 and December 2006. We retrospectively reviewed the results of surgical treatment for esophageal perforation to understand the risk factors affecting survival in patients. RESULT: Patients ranged in age from 21 to 87 years, with an average age of 52.7+/-16.98 years. Thirty-one of the patients were men and six were women. There were 23 patients (62%) with spontaneous perforations, 10 patients (27%) with a traumatic perforation, and 4 patients (11%) with an iatrogenic perforation. The site of esophageal perforation was the cervical esophagus in 5 patients, the thoracic esophagus in 31 patients, and the abdominal esophagus in one patient. Twenty-nine patients underwent primary closure of the perforation and five patients had T-tube drainage. Exclusion-diversion procedures were performed in two patients and an esophagectomy was performed in one patient. There were six cases of mortality (16.22%) and 25 cases of postoperative complications in 15 patients (40.5%). Patients that were treated later than 24 hours after detection of the perforation showed a statistically significant high morbidity and mortality rate (p<0.05). CONCLUSION: The most important risk factor of esophageal perforation was the time interval between detection of the perforation and the initiation of treatment. A prompt diagnosis and effective treatment are necessary to decrease morbidity and mortality.
Drainage ; Early Diagnosis ; Emergencies ; Esophageal Perforation ; Esophagectomy ; Esophagus ; Female ; Humans ; Male ; Postoperative Complications ; Retrospective Studies ; Risk Factors