Chronic Hypoxemia Triggers a Neuropathic Process in Chronic Obstructive Pulmonary Disease:Insight From In Vivo Neurophysiological Assessments

Background@#and PurposePeripheral neuropathies (PNs) are a common but poorly understood complication of chronic obstructive pulmonary disease (COPD). To clarify the initial trigger of a PN in COPD, we investigated the excitability of peripheral nerves in patients with COPD. @*Methods@#The automated nerve excitability test (NET) using the threshold-tracking paradigm was applied to 20 COPD patients. The recording protocol calculated the strength–duration time constant, threshold electrotonus (TE), current–threshold relationship, and recovery cycle (RC). Each NET parameter was compared with two control groups: normal controls group (NC group) and smokers without COPD group (smoker group). @*Results@#In the motor NETs, the change in the threshold in the mid-depolarizing phase of TE (40–60 ms) was smaller in the COPD group (50.7%±1.2%, mean±SEM; n=20) than in the NC group (54.5%±0.7%, n=25; p<0.01), as was the prominence of superexcitability in the RC (-22.6%±1.5% and -26.4%±1.1%, respectively; p=0.04). There were no significant differences in the sensory NETs. Comparisons between the COPD and smoker groups (n=25) also showed no differences in either the motor or sensory NETs. @*Conclusions@#The pattern of excitability in COPD revealed a membrane depolarization attributable to Na+–K+–ATPase failure in the axolemma of distal motor nerves. This finding suggests that chronic hypoxemia and adaptative process can alter axonal excitability and trigger a resultant neuropathic process that is antecedent to PN in COPD.

The Expression of Oncogenes on the Radiation-induced Apoptosis in SCK Mammary Adenocarcinoma Cell Line / 대한방사선종양학회지

PURPOSE:The expression of p53, p21/WAF/CIP, Bcl-2, and Bax underlying the radiation-induced apoptosis in different pH environments using SCK mammary adenocarcinoma cell line was investigated. MATERIALS AND METHODS: Mammary adenocarcinoma cells of A/J mice (SCK cells) in exponential growth phase were irradiated with a linear accelerator at room temperature. The cells were irradiated with 12 Gy and one hour later, the media was replaced with fresh media at a different pHs. After incubation at 37 degrees C for 0-48 h, the extent of apoptosis was determined using agarose gel electrophoresis and flow cytometry. The progression of cells through the cell cycle after irradiation in different pHs was also determined with flow cytometry. Western blot analysis was used to monitor p53, p21/WAF/CIP, Bcl-2, and Bax protein levels. RESULTS:The induction of apoptosis by irradiation in pH 6.6 medium was markedly less than that in pH 7.5 medium. The radiation-induced G2/M arrest in pH 6.6 medium lasted markedly longer than that in pH 7.5 medium. Considerable amounts of p53 and p21 proteins already existed at pH 7.5 and increased the level of p53 and p21 significantly after 12 Gy X-irradiation. An incubation at pH 6.6 after 12 Gy X-irradiation did not change the level of p53 and p21 protein levels significantly. Bcl-2 proteins were not significantly affected by radiation and showed no correlation with cell susceptibility to radiation-induced apoptosis in different pHs. An exposure to 12 Gy of X-rays increased the level of Bax protein at pH 7.5 but at pH 6.6, it was slight. CONCLUSION: The molecular mechanism underlying radiation-induced apoptosis in different pH environments using SCK mammary adenocarcinoma cell line was dependent of the expression p53 and p21/WAF/CIP proteins. We may propose following hypothesis that an acidic stress augments the radiation-induced G2/M arrest, which inhibiting the irradiated cells undergo post-mitotic apoptosis. The effects of environmental acidity on anti-apoptotic and pro-apoptotic function of Bcl-2 family was unclear in SCK mammary adenocarcinoma cell line.

Comparative Analysis of Bone Mineral Contents withDual-Energy Quantitative Computed Tomography / 대한치료방사선과학회지

PURPOSE: The Dual-Energy Quantitative Computed Tomography(DEQCT) was compared with bone equivalent K2HPO4 standard solution and ash weight of animal cadaveric trabecular bone in the measurement of bone mineral contents(BMC). METHOD AND MATERIALS: The attenuation coefficient of tissues highly depends on the radiation energy, density and effective atomic number of composition.The bone mineral content of DEQCT in this experiments was determined from empirical constants and mass attenuation coefficients of bone,fat and soft tissue equivalent solution in two photon spectra.In this experiments, the BMC of DEQCT with 80 and 120kVp X rays was compared to ash weight of animal trabecular bone. RESULTS: We obtained the mass attenuation coefficient of 0.2409, 0.5608 and 0.2206 in 80kVp, and 0.2046, 0.3273 and 0.1971cm2/g in 120kVp X-ray spectra for water, bone and fat equivalent materials, respectively.The BMC with DEQCT was acomplished with empirical constants K1=0.3232, K2=0.2450 and mass attenuation coefficients has very closed to ash weight of animal trabecular bone. The BMC of empirical DEQCT and that of manufacturing DEQCT were correlated with ash weight as a correlation r=0.998 and r=0.996, respectively. CONCLUSION: The BMC of empirical DEQCT using the experimental mass attenuation coefficients and that of manufacture have showed very close to ash weight of animal trabecular bone.