Esculetin inhibits N-methyl-D-aspartate neurotoxicity via glutathione preservation in primary cortical cultures / 한국실험동물학회지

Recently, loss of endogenous glutathione during N-methyl-D-aspartate (NMDA) receptor-mediated excitotoxic injury, and the resultant overproduction of reactive oxygen species (ROS) through an arachidonic acid cascade process in brain, have been implicated in neuronal damage in various neurodegenerative diseases. Glutathione depletion induced by L-buthionine-(S,R)-sulfoximine (BSO), an inhibitor of glutathione synthesis, is known to cause arachidonic acid-mediated excitotoxicity in primary mixed cortical cultures. The aim of this study was to investigate whether esculetin (6,7-dihydroxycoumarin), an inhibitor of lipoxygenase, protects against neurotoxicity induced by NMDA or BSO. We observed that neurotoxicity induced by NMDA but not kainic acid was attenuated by esculetin. At the same concentration (100 microM), esculetin attenuated the 45Ca2+ uptake elevation induced by NMDA. Free radical-mediated neuronal injury induced by H2O2 and xanthine/xanthine oxidase was concentration-dependently blocked by esculetin. Esculetin (1-30 microM) dose-dependently inhibited BSO-induced neuronal injury. In addition, arachidonate-induced neurotoxicity was completely blocked by esculetin. BSO also reduced glutathione peroxidase (GPx) activity, but did not change glutathione reductase (GR) activity 24 h after treatment. Esculetin dose-dependently increased GR activity, but did not alter GPx activity. These findings suggest that esculetin can contribute to the rescue of neuronal cells from NMDA neurotoxicity and that this protective effect occurs partly through NMDA receptor modulation and the sparing of glutathione depletion.

The Clinical and Pathologic Features according to Expression of Acyl Protein Thioesterase-1 (APT1) in Stage I Non-small Cell Lung Cancer / 결핵및호흡기질환

BACKGROUND: Acyl protein thioesterase-1 (APT1) is a cytosolic protein that may function in the depalmitoylation of numerous proteins, including the Ras family. However, the clinical role of depalmitoyl thioesterase in human cancer is not known. We evaluated the APT1 expression in lung cancer tissue and its clinicopathological findings according APT1 expression pattern. METHODS: APT1 expression was examined by immunohistochemistry in the tumor tissue from 79 patients, who had undergone curative surgical removal of the primary lesion; all patients had been diagnosed with stage I non-small cell lung cancer between 1993 and 2004, at Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea. RESULTS: The APT1 expression was seen in 50 out of 79 (63.3%) cases. The positive APT1 expression was significantly related with histologic subtype and T stage, but was not influenced by differentiation. The positive APT1 expression was not significantly related to patient age, gender, or smoking history. The median follow-up duration was 10.0 years; the 5-year survival rate was 71.0%. The positive APT1 expression group showed significantly worse overall survival and worse disease-free survival without statistical significance. CONCLUSION: We conclude that positive APT1 expression in stage I lung cancer after surgery is closely associated with overall survival. To evaluate APT1 as a prognostic marker in lung cancer, comprehensive studies on advanced stage cases are needed.

Cardiac Arrhythmias under General Anesthesia Using Enflurane / 대한마취과학회지

The large part of pathophysiology of cardiac arrhythmias has been clarified but still arrhythmias have bothered anesthesiologists. This study was done in order to investigate the incidence and nature of arrhythmias using Holter monitor for complete study during enflurane anesthesia. The patients were randomly allocated to two groups. Group I received succinylcholine 1.5 mg/kg, and Group II vecuronium 0.1 mg/kg, intravenously for intubation. Continuous electrocardiographic recordings on magnetic tape were made in 34 patients undergoing tympanoplasty during general anesthesia (thiopental(5 mg/kg)-muscle relaxants induction, and N2O(50%)-O2-enflurane(1.2%)-pancuronium maintenance). After completion of the recordings, the tapes were scanned to detect changes in rhythm using the analyzer. Complexes were further studied by readouts on standard ECG paper. The results were as follows: 1) The number of patients(n=14) who exhibited arrhythmias during anesthetic maintenance was significantly greater than that(n=4) during induction. 2) The incidence of occurrence of cardiac arrhythmias was 64.7%. There was no difference between two groups. If sinus tachycardia included, the incidence reached at 94.1%. 3) The frequency of supraventricular arrhythmias was more than two times that of ventricular ones. The arrhythmias occuning at the AV junction were the most common, and VPCs the second most common 4) There was no effect on the frequency in arrhythmia occurrence, of age, gender, preoperative ECG findings, intraoperative serum K(+), and intraoperative PaCO2 The discrepancy in the incidence of arrhythmia occurrence between complete and incomplete studies tells that great caution should be paid perioperatively, especially to the patients who have cardiovascular disorders.