• Korean Journal of Veterinary Research
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• v.41 no.4
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• pp.571-578
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• 2001

To evaluate if the apoptotic fragment assay could be used to estimate the dose prediction after radiation exposure, we examined apoptotic mouse crypt cells per 1,000 cells after whole body $^{60}Co$ $\gamma$-rays and 50MeV ($p{\rightarrow}Be^+$) cyclotron fast neutron irradiation in the range of 0.25 to 1 Gy, respectively. The incidence of apoptotic cell death rose steeply at very low doses up to 1 Gy, and radiation at all doses tigger rapid changes in crypt cells in stem cell region. These data suggest that apoptosis may play an important role in homeostasis of damaged radiosensitive target organ by removing damaged cells. The curve of dose-effect relationship for the data of apoptotic fragments was obtained by the linear-quadratic model $y=0.18+(9.728{\pm}0.887)D+(-4.727{\pm}1.033)D^2$ ($r^2=0.984$) after $\gamma$-rays irradiation, while $y=0.18+(5.125{\pm}0.601)D+(-2.652{\pm}0.7000)D^2$ ($r^2=0.970$) after neutrons in mice. The dose-response curves were linear-quadratic, and a significant dose-response relationship was found between the frequency of apoptotic cell and dose. These data show a trend towards increase of the numbers of apoptotic crypt cells with increasing dose. Both the time course and the radiation dose-response curve for high and low linear energy transfer (LET) radiation modalities were similar. The relative biological effectiveness (RBE) value for crypt cells was 2.072. In addition, there were significant peaks on apoptosis induction at 4 and 6h after irradiation, and the morpholoigcal findings of the irradiated groups were typical apoptotic fragments in crypt cells that were hardly observed in the control group. Thus, apoptosis in crypt cells could be a useful in vivo model for studying radio-protective drug sensitivity or screening test, microdosimetric indicator and radiation-induced target organ injury. Since the apoptotic fragment assay is simple, rapid and reproducible in the range of 0.25 to 1 Gy, it will also be a good tool for evaluating the dose response of radiation-induced organ damage in vivo and provide a potentially valuable biodosimetry for the early dose prediction after accidental exposure.

• Korean Journal of Clinical Pharmacy
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• v.31 no.1
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• pp.44-52
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• 2021

Background: Post-transplant immunosuppression with calcineurin inhibitors (CNIs) is associated with kidney function impairment while mammalian target of rapamycin (mTOR) inhibitors, such as everolimus, can be used for its renal-sparing effects. In this study, we compared the efficacy and safety of everolimus with low dose tacrolimus (EVR+Low TAC) and conventional dose tacrolimus (TAC) in liver transplantation recipients. Methods: Medical records of recipients who received liver transplantation at Seoul National University Bundang Hospital from January 1st 2009 to December 31st 2018 were retrospectively reviewed. Cohort entry date was defined as the day everolimus was initiated and tacrolimus dosage was reduced. All patients were followed up for 1 year. Indicator of efficacy was the incidence of rejection and safety was evaluated by incidence of drug adverse events including renal function. Results: Among 118 patients, there were 40 patients (33.9%) in EVR+Low TAC group. Incidence of rejection, including both biopsy proven acute rejection and clinical rejection, was similar in two groups [7.5% (n=3) vs. 6.4% (n=5), p=1.000]. Renal dysfunction was less frequent in EVR+Low TAC [17.5% (n=7) vs. 35.9% (n=28), p=0.038]. However, incidence rates of dyslipidemia, oral ulcer were more frequent in EVR+Low TAC [45.0% (n=18) vs. 21.8% (n=17), p=0.009; 15.0% (n=6) vs. 1.3% (n=1), p=0.006]. Conclusions: In terms of prevention of rejection, EVR+Low TAC was as effective as TAC and had renal-sparing effect but was associated with increased risk of dyslipidemia and oral ulcer. This study demonstrates that EVR+Low TAC could be an alternative to liver transplant recipients with nephrotoxicity after administration of conventional dose tacrolimus.

• Journal of Nuclear Fuel Cycle and Waste Technology(JNFCWT)
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• v.13 no.1
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• pp.73-86
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• 2015

The use of complimentary indicators, other than radiation dose and risk, to assess the safety of radioactive waste disposal has been discussed in a number of publications for providing the reasonable assurance of disposal safety and convincing the public audience. In this study, the radionuclide flux was selected as performance indicator to appraise the performance of engineered barriers and natural barrier in the Wolsong low- and intermediate-level waste disposal facility. Radionuclide flux showing the retention capability by each compartment of the disposal system is independent of assumptions in biosphere model and exposure pathways. The scenario considered as the normal scenario of disposal facility has been divided into intact or degraded silo concrete conditions. In the intact silo concrete, the radionuclide flux has been assessed with respect to the radionuclide retardation performance of each engineered barrier. In the degraded silo concrete, the radionuclide flux has been explored based on the performance degradation of engineered barriers and the relative significance of natural barrier quantitatively. The results can be used to optimally design the near-surface disposal facility being planned as the second project phase. In the future, additional complimentary indicators will be employed for strengthening the safety case for improving the public acceptance of low- and intermediate-level waste disposal facility.

• Advances in Traditional Medicine
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• v.10 no.1
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• pp.1-6
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• 2010

The efficacy of the radioprotective effect of Callophyllis japonica ethyl acetate (CJEA) extract was studied by comparing it to that of amifostine, a well-known radioprotective agent, and by evaluating the dose reduction factor, an indicator of radioprotective efficacy. Pretreatment with CJEA extract (100 mg/kg body weight) prior to receiving 12 Gy irradiation significantly improved the survival of jejunal crypts at 3.5 day post-irradiation, but attenuated the level of malondialdehyde compared to vehicle alone (P < 0.01). A similar gastroprotective effect was also obtained in the amifostine-treated irradiated group (P < 0.01). The efficacy of the radioprotective effect was further confirmed by the dose reduction factor, 1.41. Collectively, these results suggest that CJEA extract is a useful radioprotectant whose efficacy is similar to that of amifostine and whose radioprotective mechanism is in part the reduction of lipid peroxidation caused by gamma irradiation.

• The Korean Journal of Physiology and Pharmacology
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• v.5 no.4
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• pp.333-342
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• 2001

Adriamycin is a commonly used chemotherapeutic agent for cancer, including acute leukemia, lymphoma, and a number of solid human tumors. However, recent studies have recognized severe cardiotoxicity after an acute dose, which are likely the result of generation of free radicals and lipid peroxidation. Therefore, the clinical uses of adriamycin have been limited. Melatonin, the pineal gland hormone known for its ability to modulate circardian rhythm, has recently been studied in its several functions, including cancer growth inhibition, stimulating the immune system, and acting as an antioxidant and radical scavenging effects. In the present study, we evaluated the effect of melatonin administration on adriamycin-induced cardiotoxicity in rat. Heart slices were prepared using a Stadie-Riggs microtome for the measurement of malondialdehyde (MDA) content used as an index of lipid peroxidation and lactate dehydrogenase (LDH) release as an indicator of lethal cell injury. Serious adriamycin-induced lethality was observed in rat by a single intraperitoneal injection in a dose-dependent manner. A single injection of adriamycin (25 mg/kg, i.p.) induced a lethality rate of 86%, with melatonin (10 mg/kg s.c. for 6 days) treatment reducing the adriamycin-induced lethality rate to 20%. The severe body weight loss caused by adriamycin was also significantly attenuated by melatonin treatment. Treatment of melatonin marked reduced adriamycin-induced the levels of MDA formation and LDH release. A cell damage indicated by the loss of myofibrils, swelling of the mitochondria as well as cytoplasmic vacuolization was seen in adriamycin-treated group. Melatonin attenuated the adriamycin-induced structural alterations. These data provide evidence that melatonin prevents adriamycin-induced cardiotoxicity and might serve as a combination with adriamycin to limit free radical-mediated cardiotoxicity.

• Journal of Ginseng Research
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• v.21 no.2
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• pp.132-140
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• 1997

The effects of ginsenosides purified from red ginseng on platelet aggregation were investigated. Preincubation of washed platelets from rats with either ginsenoside Rg3, ginsenosides non-polar fraction (G-NPF), ginsenoside Rg1(Rg1) or ginsenosides polar fraction(G-PF) reduced the plytelet aggrelation induced by collagen in a dose-dependent manner, whereas ginsenoside Rg2 failed to inhibit the aggregation. Their IC50 values of Rg3, G-NPF, Rgl, and G-PF were 8.7$\pm$1.0, 150.3$\pm$0.1, 369.9$\pm$ 1.0, 606.211.3 $\mu\textrm{g}$/ml, respectively. Aggrelation induced by thrombin was also inhibited by Rg3 and G-NPF with IC50 being 5.2$\pm$ 1.1 and 66.5$\pm$0.8 $\mu\textrm{g}$/ml, respectively. The alterations of Intracellular Ca2+ concentration in platelets were monitored using fura-2 as a fluorescent Ca2+ indicator. Both Ca2+ release from internal stores and Ca2+ influx into cytosol were suppressed by Rg3. Rg3 also inhibited granular release of ATP and TXA2 formation induced by thrombin in a dose-dependent manner in the washed platelets. Rg3 also inhibited Aggregation and ATP release from human platelets induced by collagen to a similar extent as were observed in rat platelets. In conclusion, Rg3 is a Potent anti-aggregating component in ginsenosides and may exert its anti-aggrega1ing activity by decreasing TXAa formation and granular secretion in platelets, most likely by inhibiting Ca2+ influx and Ca2+ mobilization from intracellular stores. Thus ginseng may contribute to the prevention and treatment of thrombosis.

• KOREAN JOURNAL OF CROP SCIENCE
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• v.50 no.2
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• pp.84-90
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• 2005

The effects of UV-B radiation on the seedling growth, carbohydrate metabolism and antioxidants activities of rice (Oryza sativa L.) were investigated under environmentally controlled chamber. Supplementary UV­B radiation reduced dry matter as well as leaf area, there­fore, relative growth rates (RGR) of seedlings were decreased by up to half compared to control. Photosynthetic products such as soluble sugars and starch were rapidly and significantly reduced by within 1 day of enhanced UV-B radiation due to the inhibition and degradation of photosynthetic processes and thylakoid membrane integrity. In our study, nonstructural carbohydrate levels were proved to be a main indicator on UV-B­induced stress. The behavior of SOD, CAT, APX and POD activities was monitored in the leaves of rice seedlings subjected to UV-B radiation. Under UV-B treatments, SOD activity was initially increased, whereas CAT and POD activities were slowly and slightly increased. However, APX activity showed no presumable results with an increase of UV-B dose. In leaves of rice seedlings, supplementary UV-B radiation caused an increase in free putrescine and spermidine, however spermine remained unaltered, although 24-hrs UV-B treatment slightly increased. This result presumes that an excess UV-B dose may induce ethylene biosynthesis (senescence) rather than polyamine biosynthesis (defense).

• Biomolecules & Therapeutics
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• v.21 no.4
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• pp.290-298
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• 2013

This study examined the effects of calcium (Ca) gluconate on collagen-induced DBA mouse rheumatoid arthritis (CIA). A single daily dose of 200, 100 or 50 mg/kg Ca gluconate was administered orally to male DBA/1J mice for 40 days after initial collagen immunization. To ascertain the effects administering the collagen booster, CIA-related features (including body weight, poly-arthritis, knee and paw thickness, and paw weight increase) were measured from histopathological changes in the spleen, left popliteal lymph node, third digit and the knee joint regions. CIA-related bone and cartilage damage improved significantly in the Ca gluconate-administered CIA mice. Additionally, myeloperoxidase (MPO) levels in the paw were reduced in Ca gluconate-treated CIA mice compared to CIA control groups. The level of malondialdehyde (MDA), an indicator of oxidative stress, decreased in a dose-dependent manner in the Ca gluconate group. Finally, the production of IL-6 and TNF-${\alpha}$, involved in rheumatoid arthritis pathogenesis, were suppressed by treatment with Ca gluconate. Taken together, these results suggest that Ca gluconate is a promising candidate anti-rheumatoid arthritis agent, exerting anti-inflammatory, anti-oxidative and immunomodulatory effects in CIA mice.

• Archives of Pharmacal Research
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• v.25 no.4
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• pp.505-510
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• 2002

An improved kinetic assay for prekallikrein activator (PKA), a potential vasodilator, has been developed to be used as an indicator for quality control during production of human albumin preparations. It consists of two reaction stages. In the first stage, PKA and prekallikrein are incubated at $37^{\circ}C$ for 45 min to allow the transformation into kallikrein. Kallikrein, a serine protease, catalyzes the splitting of p-nitroaniline (pNA) from its substrate H-D-Pro-Phe-Arg-pNA(S-2302). The rate at which pNA is released was measured spectrophotometrically at 405 nm. Prekallikrein, a substrate of PKA was purified by DEAE ion-exchange chromatography and the major potential variations in the assay were optimized; pH 8.0 and 150 mM sodium chloride were chosen to give a proper ionic strength. Reaction times in the range of 10 to 360 min provided linear dose-response curves. The concentration of prekallikrein was adjusted to fall between 1:1 and 1:3 dilutions to generate a linear standard calibration curve. Under the optimized conditions, reproducibility was checked. In a precision test, the coefficient of variation (CV) stayed within ${\pm}4%$ and the dose-response curve showed a good correlation (${r^2}=0.999$). An accuracy test with an international standard of PKA afforded a mean recovery of 97.5%.

• Journal of the Korean Society of Radiology
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• v.10 no.7
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• pp.477-482
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• 2016

This study is tried to determine whether the management of medical radiation is well handled by comparison the guidelines of KFDA(korea food & drug administration) with analysis of dose indicator in mammography. As a method, it is analysed that kVp, exposure time, mAs, compressed breast thickness, average glandular dose and body mass index that were classified in the examination of both breasts by CC(cranio-caudal) and MLO(medio-lateral oblique) with EMR(electronic medical record) and dose report that were sent to the PACS(picture archiving communication system). As a result, in the site inspection according to the age, Compressed breast thickness in CC and MLO were the thickest of 45.6 mm and 49.6 mm in the 50-59 year old respectively. In the overall average compressed breast thickness, CC were 44.2 mm and MLO were 48.9 mm. MLO has more thick by 4.7 mm. In average glandular dose, CC were 1.05 mGy and MLO were 1.14 mGy. MLO has higher by 0.09 mGy than CC. As the compressed breast thickness increases 10mm, CC and MLO increases 0.15 mGy and 0.17 mGy respectively. When it was compared with the average glandular dose of 1.16 mGy per 1 film presented by KFDA, CC was showed 1.05 mGy. However, the 60 mm or more was found to exceed a 1.30 mGy. Also, As the compressed breast thickness was higher, body mass index showed high score. And in the case of 25 or more in the obese body index according to body mass index, it was showed obesity in case of the compressed breast thickness was more than 50mm.