• Applied Microscopy
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• v.27 no.3
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• pp.333-346
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• 1997

The ischemia and reperfusion injury of the skeletal muscles is caused by generation of reactive oxygen during ischemia and reperfusion. It is well known that over 4 hours of ischemia injures the skeletal muscles irreversibly. The author has demonstrated the effects of SOD (superoxide dismutase), DMTU (dimethyl thiourea) and ischemic preconditioning on ultrastructural changes of the muscle fibers in the rectus femoris muscles after 4 hours of ischemia and 1 day and 3 days of reperfusion. A total of 72 healthy Sprague-Dawley rats weighing from 200 gm to 250 gm were used as experimental animals. Under urethane(1.15 g/kg, IP, 2 times) anesthesia, lower abdominal incision was done and the left common iliac artery was occluded by using vascular clamp for 4 hours. The left rectus femoris muscles were obtained at 1 and 3 days after the removal of vascular clamp. The SOD (15,000 unit/kg) or DMTU (500 mg/kg) were administered intraperitoneally at 1 hour before induction of ischemia. The ischemic preconditioned group underwent three episodes of 5 minutes occlusion and 5 minutes reperfusion followed by 4 hours of ischemia and 1 day and 3 days of reperfusion. The specimens were sliced into $1mm^3$ and prepared by routine methods for electron microscopic observation. All specimens were stained with uranyl acetate and lead citrate and then observed with Hitachi-600 transmission electron microscope. The results were as follows: 1. SOD or DMTU alone did not affect the ultrastructure of muscle fibers in the rectus femoris muscles. The electron density of mitochondrial matrix was decreased by ischemic preconditioning. 2. Dilated cisternae of sarcoplasmic reticulum, triad, mitochondria and the loss of myofilament in the sarcomere were observed in the 4 hours ischemia and 1 day reperfused rectus femoris muscles. Markedly changed sarcoplasmic reticulum, triad, disordered or loss of myofilament, indistinct A-band and I-band, and irregular electron lucent M -line and Z-line are seen in the 4 hours ischemia and 3 days reperfused rectus femoris muscles. 3. SOD reduced the changes of organelles in the muscle fibers of the 4 hours ischemia and 1 day reperfused rectus femoris muscles of the rats, but SOD did not affect the changes of muscle fibers in the 4 hours ischemia and 3 days reperfused muscles. On the other hand, DMTU markedly attenuated considerably the ultrastructural change of the 4 hours ischemia and 1 day or 3 days reperfused rectus femoris muscles. 4. By the ischemic preconditioning, the change was attenuated remarkably in the 4 hours ischemia and 1 day reperfused rectus femoris muscles. As the ischemic reperfused changes of muscle fibers were regenerated or recovered by ischemic preconditioning, the ultrastructures of them were similar to those of normal control in the 4 hours ischemia and 3 days reperfused rectus formoris muscles. Consequently, it is suggested that DMTU is stronger inhibitor to ischemic reperfused change than SOD. The ischemia and reperfusion-induced muscular damage is remarkably inhibited by ischemic preconditioning.

• Korean Journal of Radiology
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• v.23 no.9
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• pp.911-920
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• 2022

Objective: ⁶⁸Ga-NGUL is a novel prostate-specific membrane antigen (PSMA)-targeting tracer based on Glu-Urea-Lys derivatives conjugated to a 1,4,7-triazacyclononane-N,N',N''-triacetic acid (NOTA) chelator via a thiourea-type short linker. This phase I clinical trial of ⁶⁸Ga-NGUL was conducted to evaluate the safety and radiation dosimetry of ⁶⁸Ga-NGUL in healthy volunteers and the lesion detection rate of ⁶⁸Ga-NGUL in patients with prostate cancer. Materials and Methods: We designed a prospective, open-label, single-arm clinical trial with two cohorts comprising six healthy adult men and six patients with metastatic prostate cancer. Safety and blood test-based toxicities were monitored throughout the study. PET/CT scans were acquired at multiple time points after administering ⁶⁸Ga-NGUL (2 MBq/kg; 96-165 MBq). In healthy adults, absorbed organ doses and effective doses were calculated using the OLINDA/EXM software. In patients with prostate cancer, the rates of detecting suspicious lesions by ⁶⁸Ga-NGUL PET/CT and conventional imaging (CT and bone scintigraphy) during the screening period, within one month after recruitment, were compared. Results: All 12 participants (six healthy adults aged 31-32 years and six prostate cancer patients aged 57-81 years) completed the clinical trial. No drug-related adverse events were observed. In the healthy adult group, ⁶⁸Ga-NGUL was rapidly distributed, with the highest uptake in the kidneys. The median effective dose coefficient was calculated as 0.025 mSv/MBq, and cumulative activity in the bladder had the highest contribution. In patients with metastatic prostate cancer, 229 suspicious lesions were detected using either ⁶⁸Ga-NGUL PET/CT or conventional imaging. Among them, ⁶⁸Ga-NGUL PET/CT detected 199 (86.9%) lesions and CT or bone scintigraphy detected 114 (49.8%) lesions. Conclusion: ⁶⁸Ga-NGUL can be safely applied clinically and has shown a higher detection rate for the localization of metastatic lesions in prostate cancer than conventional imaging. Therefore, ⁶⁸Ga-NGUL is a valuable option for prostate cancer imaging.

• Tuberculosis and Respiratory Diseases
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• v.46 no.5
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• pp.636-644
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• 1999

Background : Tumor necrosis factor(TNF) has been considered as an important candidate for cancer gene therapy based on its potent anti-tumor activity. The mechanisms of TNF cytotoxicity are not clearly understood and some has reported that reactive oxygen species(ROS) might be associated with them, but there is controversy about antioxidant effect on TNF cytotoxicity. This study was designed to compare the TNF cytotoxicity after antioxidant pretreatment with that of control to evaluate the role of ROS in the mechanism of TNF cytotoxicity. Method : We compared the TNF cytotoxicies to WEHI164(murine fibrosarcoma cell line) and ME180(human cervix cancer cell line) after antioxidant pretreatment with those of control by MIT(dimethylthiazolyl-diphenyltetrazolium bromide) assay. Results : In the control group, the TNF cytotoxicities were $92.2{\pm}2.8%$(WEHI164) and $59.9{\pm}7.0%$(MEl80). In the TMTU(tetramethyl thiourea) pretreatment group, those were $91.4{\pm}3.7%$ and $74.6{\pm}7.0%$. In the PMZ(promethazine) pretreatment group, those were $90.2{\pm}2.5%$ and $62.5{\pm}5.7%$. In the BHT(butylated hydroxytoluene) pretreatment group, those were $93.2{\pm}1.3%$ and $66.3{\pm}6.1%$. So there was no reduction in TNF cytotoxicity after antioxidants pretreatment. Conclusion : The ROS may not have major role in the mechanisms of TNF cytotoxicity.