• 대한한방내과학회지
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• 제35권1호
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• pp.37-49
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• 2014

목적 및 방법 : 본 연구에서는 한의학에서 전통적으로 신경보호 약물로 사용되어온 총명탕 물 추출물의 급성 독성증상을 관찰하기 위하여 한국식품의약품안전청 고시 제 2009-116호에 따라 암수 ICR마우스 단회 경구투여 독성 실험을 실시하였다. 반수치사량, 개략적치사량, 표적장기 등을 관찰하기 위하여, 수율 9.70% 총명탕 물 추출물 2,000, 1,000 및 500 mg/kg을 암수 마우스에 단회 경구 투여하고, 투여 후 14일 동안의 임상증상, 사망례, 체중 및 증체량의 변화 및 부검소견을 관찰하였으며, 투여 14일 후 14개 주요 실질 장기에 대한 중량 및 조직병리학적 관찰을 실시하였다. 또한 별도의 암수 매체 대조군을 두어 그 결과를 비교하였다. 결 과 : 본 실험의 결과, 설치류 최대 한계투여 용량인 2,000 mg/kg까지 총명탕 물 추출물 투여와 관련된 사망례가 인정되지 않았으며, 암수 매체 대조군을 포함하여, 모든 실험군에 걸쳐 산발적으로 관찰된 일부 우발적인 육안부검 및 조직병리학적 소견을 제외하고, 총명탕 물 추출물 투여와 관련된 임상증상, 체중 및 장기 중량의 변화, 14개 주요장기에 대한 육안부검 및 조직병리학적 소견이 인정되지 않았다. 결 론 : 따라서 마우스 단회 경구투여 독성실험에서 총명탕 물 추출물의 반수치사량 및 개략적 치사량은 각각 설치류 투여 한계용량인 2,000 mg/kg 이상으로 관찰되어, 매우 안전한 약물로 판단되며, 임상사용에는 별 다른 문제를 일으키지는 않을 것으로 판단된다.

• 대한한방내과학회지
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• 제32권4호
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• pp.599-609
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• 2011

Objectives : The aim of this study was to evaluate the single oral dose toxicity and safety of Bojungikgi-tang (Buzhongyiqi-tang) and fermented Bojungikgi-tang (Buzhongyiqi-tang) extracts in male and female ICR mice. Methods : In the single oral dose toxicity study, non-fermented and fermented Bojungikgi-tang (Buzhongyiqi-tang) were administered to male and female ICR mice as an oral dose of 1250, 2500 and 5000 mg/kg. Changes of body weights, general behaviors, adverse effects and mortality were determined throughout the experimental period. Hematological parameters, serum chemistry, organ weights and necropsy findings were evaluated at the end of the experiment. Results : There was no mortality or sign of toxicity in the single oral dose toxicity study. There were also no significant differences in body weights, organ weights, and hematological parameters, serum chemistry values between treatment and control groups. Conclusions : The results obtained in this study suggest that the 50% lethal dose of fermented Bojungikgi-tang (Buzhongyiqi -tang) in both female and male mice can be considered as well over 5,000 mg/kg, so these medicines can be safe in clinics.

• Nuclear Engineering and Technology
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• 제55권1호
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• pp.248-253
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• 2023

Directly, it is not possible to measure the absorbed dose of radiopharmaceuticals in the organs of the human body. Therefore, simulation methods are utilized to estimate the dose in distinct organs. In this study, individual organs were separately considered as the source organ or target organ to calculate the mean absorption dose, which SAF and S factors were then calculated according to the target uptake via MIRD method. Here, ^99mTc activity distribution within the target was analyzed using the definition and simulation of ideal organs by summing the fraction of cumulative activities of the heart as source organ. Thus, GATE code was utilized to simulate the Zubal humanoid phantom. To validate the outcomes in comparison to the similar results reported, the accumulation of activity in the main organs of the body was calculated at the moment of injection and cardiac rest condition after 60 min of injection. The results showed the highest dose absorbed into pancreas was about 21%, then gallbladder 18%, kidney 16%, spleen 15%, heart 8%, liver 8%, thyroid 7%, lungs 5% and brain 2%, respectively, after 1 h of injection. This distinct simulation model may also be used for different periods after injection and modifying the prescribed dose.

• The Korean journal of internal medicine
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• 제39권3호
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• pp.501-512
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• 2024

Background/Aims: Optimal risk stratification based on simplified geriatric assessment to predict treatment-related toxicity and survival needs to be clarified in older patients with diffuse large B-cell lymphoma (DLBCL). Methods: This multicenter prospective cohort study enrolled newly diagnosed patients with DLBCL (≥ 65 yr) between September 2015 and April 2018. A simplified geriatric assessment was performed at baseline using Activities of Daily Living (ADL), Instrumental ADL (IADL), and Charlson's Comorbidity Index (CCI). The primary endpoint was event-free survival (EFS). Results: The study included 249 patients, the median age was 74 years (range, 65-88), and 125 (50.2%) were female. In multivariable Cox analysis, ADL, IADL, CCI, and age were independent factors for EFS; an integrated geriatric score was derived and the patients stratified into three geriatric categories: fit (n = 162, 65.1%), intermediate-fit (n = 25, 10.0%), and frail (n = 62, 24.9%). The established geriatric model was significantly associated with EFS (fit vs. intermediate-fit, HR 2.61, p < 0.001; fit vs. frail, HR 4.61, p < 0.001) and outperformed each covariate alone or in combination. In 87 intermediate-fit or frail patients, the relative doxorubicin dose intensity (RDDI) ≥ 62.4% was significantly associated with worse EFS (HR, 2.15, 95% CI 1.30-3.53, p = 0.002). It was related with a higher incidence of grade ≥ 3 symptomatic non-hematologic toxicities (63.2% vs. 27.8%, p < 0.001) and earlier treatment discontinuation (34.5% vs. 8.0%, p < 0.001) in patients with RDDI ≥ 62.4% than in those with RDDI < 62.4%. Conclusions: This model integrating simplified geriatric assessment can risk-stratify older patients with DLBCL and identify those who are highly vulnerable to standard dose-intensity chemoimmunotherapy.

• 동의생리병리학회지
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• 제18권3호
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• pp.900-907
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• 2004

The antiproliferative effect of the water extract of the branch and root bark of Ulmi Pumilae Cortex(WEUPC) was investigated on the p53-negative human leukemia cell line (HL-60). A dose- and time-dependent inhibition of cell growth was observed; this effect appears to be due to induction of apoptosis. Involvement of oxidative stress is indicated by a dose-dependent increase in intracellular reactive oxygen species levels. In addition. anti-apoptic effect was observed in the cells simultaneously treated with WEUPC and the anti-oxidant N-acetylcysteine. WEUPC did not affect the anti-apoptotic Bcl-2 and the pro-apoptotic Bax, whereas p21/sup WAF1/CIPl/ was enhanced in a dose- and time-dependent fashion; this effect was partially inhibited by N-acetylcysteine. The increase in p21/sup WAF1/CIPl/ was accompanied by a parallel accumulation of cells in the G1 phase of the cycle. These results suggest that the p53-independent induction of p21/sup WAF1/CIP/ and the induction of apoptosis may mediate the anti proliferative effect of WEUPC at least in this study; on the basis of this observation, WEUPC could be proposed as an useful adjunct to the treatment of p53-deficient tumors, which are often refractory to standard chemotherapy.

• 대한한의학방제학회지
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• 제15권2호
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• pp.99-111
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• 2007

In the present study, the anti-inflammatory effect of "Jungcheonhwadamgangki-tang ga Antler" water extract was tested in Xylene-Application mouse ear acute inflammation model. The test articles were once dosed before Xylene-Application, and the changes on body weight and ear weights and histopathological observation of induced ear were conducted with ear histomorphometry. The obtained results were as follows. The increases of absolute and relative ear weight detected in vehicle control compared to that of sham, were significantly and dose-dependently inhibited by Jungcheonhwadamgangki-tang ga Antler in the present study. A classic acute inflammatory histological changes such as subcutaneous edema, thickness and infiltration of inflammatory cells, was detected in vehicle control. However, these histological changes were significantly and dose-dependently inhibited by Jungcheonhwadamgangki-tang ga Antler. In addition, the increases of ear thickness half and thickness full detected in the vehicle control were also dose-dependently decreased in the all Jungcheonhwadamgangki-tang ga Antler-dosing groups. Base on these results, it is concluded that Jungcheonhwadamgangki-tang ga Antler extracts has clear anti-inflammatory effect on the acute inflammation such as bronchial asthma.

• 동의생리병리학회지
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• 제23권5호
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• pp.1145-1153
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• 2009

The object of this study was to obtain acute information single oral dose toxicity of Mahwangbujaseshin-tang extracts, with mouse bone marrow cell micronucleus test for detecting possible genotoxicity. In order to observe the 50% lethal dose, approximate lethal dosage, maximum tolerance dosage and target organs, test articles were once orally administered to ICR mice at dose levels of 2000, 1000, 50 mg/kg according to the recommendation of KFDA Guidelines. The mortality and changes on body weight, clinical signs and gross observation were monitored during 14 days after dosing according to KFDA Guidelines with organ weights of 12 types of principle organs. In addition, after twice oral treatment of Mahwangbujaseshin-tang extracts 2000, 1000 and 500 mg/kg, we checked the changes on the number of MNPCE. We could not find any mortality, clinical signs, changes in the body weight and gross findings upto 2000 mg/kg treated group. The limited dosages in rodents except for increases of lymphoid organ weights and hypertrophy encounted as results from pharmacological effects of Mahwangbujaseshin-tang extracts, immune modulator effects with some sporadic accidental findings not toxicological signs. No evidence of increases of MNPCE numbers were also detected in all three different dosages of Mahwangbujaseshin-tang extracts treated mice. The results obtained in this study suggest that the LD50 and ALD of Mahwangbujaseshin-tang extracts in mice were considered as over 2000 mg/kg because no mortalities were detected upto 2000 mg/kg that was the highest dose recommended by KFDA and OECD. And the results of mouse bone marrow micronucleus test of Mahwangbujaseshin-tang extracts is negative results.

• 동의생리병리학회지
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• 제24권1호
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• pp.124-133
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• 2010

The object of this study was to obtain acute information single oral dose toxicity of Mahwangbujaseshin-tang extracts, with mouse bone marrow cell micronucleus test for detecting possible genotoxicity. In order to observe the 50% lethal dose, approximate lethal dosage, maximum tolerance dosage and target organs, test articles were once orally administered to ICR mice at dose levels of 2000, 1000, 50 mg/kg according to the recommendation of KFDA Guidelines. The mortality and changes on body weight, clinical signs and gross observation were monitored during 14 days after dosing according to KFDA Guidelines with organ weights of 12 types of principle organs. In addition, after twice oral treatment of Mahwangbujaseshin-tang extracts 2000, 1000 and 500 mg/kg, we checked the changes on the number of MNPCE. We could not find any mortality, clinical signs, changes in the body weight and gross findings upto 2000 mg/kg treated group. The limited dosages in rodents except for increases of lymphoid organ weights and hypertrophy encounted as results from pharmacological effects of Mahwangbujaseshin-tang extracts, immune modulator effects with some sporadic accidental findings not toxicological signs. No evidence of increases of MNPCE numbers were also detected in all three different dosages of Mahwangbujaseshin-tang extracts treated mice. The results obtained in this study suggest that the LD50 and ALD of Mahwangbujaseshin-tang extracts in mice were considered as over 2000 mg/kg because no mortalities were detected upto 2000 mg/kg that was the highest dose recommended by KFDA and OECD. And the results of mouse bone marrow micronucleus test of Mahwangbujaseshin-tang extracts is negative results.

• Journal of Radiation Protection and Research
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• 제46권4호
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• pp.170-177
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• 2021

Background: The International Commission on Radiological Protection is preparing to provide reference dose coefficients for environmental radioiodine intake based on newly developed age-specific biokinetic models. However, the biokinetics of iodine has been reported to be strongly dependent on the dietary intake of stable iodine; for example, the thyroidal uptake of iodine may be substantially lower in iodine-rich regions than in iodine-deficient regions. Therefore, this study attempted to establish a system of age-specific thyroid dose estimation for South Koreans, whose daily iodine intakes are significantly higher than that of the world population. Materials and Methods: Korean age-specific biokinetic parameters and thyroid masses were derived based on the previously developed Korean adult model and the Korean anatomical reference data for adults, respectively. This study complied with the principles used in the development of age-specific biokinetic models for world population and used the ratios of baseline values for each age group relative to the value for adults to derive age-specific values. Results and Discussion: Biokinetic model predictions based on the Korean age-specific parameters showed significant differences in iodine behaviors in the body compared to those predicted using the model for the world population. In particular, the Korean age-specific thyroid dose coefficients for ¹²⁹I and ¹³¹I were considerably lower than those calculated for the world population (25%-76% of the values for the world population). Conclusion: These differences stress the need for Korean-specific internal dose assessments for infants and children, which can be achieved by using the data calculated in this study.

• 대한한방내과학회지
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• 제28권1호
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• pp.166-175
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• 2007

Objectives : This study was designed to evaluate the neuroprotective effect of Cirsium japonicum and Silibinin on lipopolysaccharide-induced inflammation in BV2 microglial cells. Methods : We studied on the neuroprotective effect of lipopolysaccharide-induced inflammation using MTS assay, western blot, and nitric oxide detection on mouse BV2 microglial cells. Results : Cirsium japonicum dose-dependently (50${\mu}g/ml$${\sim}$$250{\mu}g/ml$) inhibited nitrite production and iNOS expression in lipopolysaccharide-induced BV2 microglia and also significantly reduced lipopolysaccharide-induced COX-2 activation in western blot. Silibinin dose-dependently (10${\mu}M$${\sim}$$100{\mu}M$) inhibited nitrite production and iNOS expression in lipopolysaccharide-induced BV2 microglial cells. Silibinin also significantly reduced lipopolysaccharide-induced COX-2 activation in western blot. Conclusion : These effects of neuroprotection related to anti-inflammation suggest that Cirsium japonicum and Silibininmay be useful candidates for the development of a drug for related neurodegenerative diseases.