• 대한한의학회지
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• 제29권1호
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• pp.179-191
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• 2008

Background and Objectives : Atopic dermatitis is a recurrent or chronic eczematous skin disease with severe pruritus,and has increased in Korea. Although the pathogenic mechanisms of atopic dermatitis are yet unknown, recently skin barrier dysfunction and hyperresponsive Th2 cells in the acute phase have been reported as important mechanisms. Cheonggi-san(CGS) is used in oriental clinics for treatingacute skin lesions of eczema or urticaria. There have been no studies on the therapeutic mechanism of CGS for curing atopic dermatitis. We aimed to find out the therapeutic effects of its internaluse on atopic dermatitis-like skin lesions, induced in NC/Nga mice by the mite antigen D. pteronyssinus and disrupting skin barrier. Materials and Methods : The NC/Nga mice were classified into three groups: control group, atopic dermatitis elicitated group(AD), and CGS treated group (CT). Atopic dermatitis-like skin lesions were induced on the back of female NC/Nga mice, 12 weeks of age, by tape stripping, 5% SDS applied to disrupt skin barrier and painting 3 times a week with D. pteronyssinus crude extract solution for 3 weeks. CT was treated with CGS orally after atopic dermatitis was elicitated. We observed changes of skin damage, mast cells, substance P, angiogenesis, skin barrier, Th2 cell differentiation, nuclear factor-${\kappa}B(NF-{\kappa}B)$ p65 activation and COX-2 in NC/Nga mice with atopic dermatitis-like skin lesions. Results : The skin damages as eczema were seenin AD, but mitigated in CT. The degranulated mast cells in dermal papillae increased in AD, but decreased in CT. The substance P positive reacted cells in CT remarkably decreased. The angiogenesis increased in AD, but decreased in CT. The decrease of lipid deposition and ceramide in AD was seen, but anincrease of lipid deposition and ceramide in CT was seen. The distribution of IL-4 positive reacted cells in dermal papillae increased in AD, but decreased in CT. The distribution of NF-${\kappa}B$ p65 positive reacted cells & COX-2 positive reacted cells in CT decreased. Conclusion : The results may suggest that the CGS per os decreases the dysfunction of the skin barrier, inhibits Th2 cell differentiation and inhibits NF-${\kappa}B$ p65 activation in NC/Nga mice with atopic dermatitis-like skin lesions.

• Parasites, Hosts and Diseases
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• 제47권4호
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• pp.345-351
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• 2009

The $\beta$-glucans derived from yeast cell walls have been reported for having many immunomodulatory activities in vivo and in vitro. In this study, Aureobasidium-derived soluble branched (1,3-1,6) $\beta$-glucan (Sophy $\beta$-glucan) was checked for natural killer (NK) activity and for the production of IFN-$\gamma$ and IL-4 in Leishmania amazonensis infection. The main experiment was performed with a group of female C57BL/6 and BALB/c mice, orally supplemented with 5% of Sophy $\beta$-glucan and infected with promastogotes of L. amazonensis ($1\;{\times}\;10^7$) into the footpad. Increase in the footpad thickness with time was observed in BALB/c mice in spite of the oral Sophy $\beta$-glucan supplement, but it was less in C57BL/6 mice. The difference in overall mean footpad thickness between 'infection only' versus 'infection + glucan' groups was statistically significant (P < 0.001). High NK activity in C57BL/6 than BALB/c mice was observed in 'glucan only' group compared to the control group and also in 'infection + glucan' group compared to 'infection only' group. The difference in the NK activity among these groups was significant (P < 0.05). The IFN-$\gamma$ level increased at weeks 7 and 8 post-infection in C57BL/6 mice and was significantly high in 'infection + glucan' group compared to the 'infection only' group (P < 0.05). IL-4 levels did not increase up to detectable levels throughout the study. The results led a conclusion that Sophy $\beta$-glucan enhances NK activity and cellular immunity in L. amazonensis-infected mice.

• 한국환경성돌연변이발암원학회지
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• 제21권1호
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• pp.1-8
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• 2001

We have synthesized $^{99m}$Tc-mercaptoacetyltriglycine (MAG3)-biocytin as a new imaging agent for hepatobiliary scintigraphy. The aim of this study was to evaluate the usefulness of $^{99m}$Tc-MAG3-biocytin scintigraphy in differentiating carbon tetrachloride ( $CCl_4$)-induced hepatotoxicity from $\alpha$-naphthylisothiocyanate (ANIT)-induced cholestasis in mice, which reflecting the differential diagnosis of neonatal jaundice caused by neonatal hepatitis from congenital biliary atresia in humans. Methods: Balb/c mice (female, 20 g, n=4-6) were pretreated with $CCl_4$(0.5 or $1.0m\ell$/kg) and ANIT ($150 or 300 m\ell$/kg) 18 h before scintigraphy. Biochemical and histopathological examinations showed a pattern of typical acute hepatitis (increase of transaminases and hepatocellular necnsis) in $CCl_4$-treated mice and cholestasis (increase of alkaline phosphatase and ${\gamma}$-glutamyltransferase, and biliary hyperplasia) in ANIT-treated mice, respectively, Mice were fasted at least 4 hr prior to the intravenous injection of $^{99m}$Tc-MAG3-biocytin (18.5 MBq/20$\mu\textrm{g}$) in 2% human serum albumin in saline. Scintigraphy was performed with a ${\gamma}$-camera equipped with a 1-mm diameter pin-hole collimator for 30 min and images were acquired every 15 s. We compared the values of physical parameters, such as peak liver/heart ratio ($${\gamma}$_{max}$) and peak ratio time ($t_{max}$) far $^{99m}$Tc-MAG3-biocytin scintigraphy. Results: Scintigraphic parameters of the $CCl_4$-pretreated (0.5 $m\ell$/kg) group showed a 81.9% decrease of r$_{max}$, and 42.2% decrease of $t_{max}$, whereas the ANIT-pretreated ( $150m\ell$/kg) group showed a 53% decrease of $r_{max}$, and 2.36-fold increase of $t_{max}$, (P<0.05). These results demonstrate that the decrease of $r_{max}$ and the shortening of $t_{max}$ are characteristic features for hepatotoxicity, in contrast to the increase of $t_{max}$ and decrease of $r_{max}$ for biliary hyperplasia. Conclusion: $^{99m}$Tc-MAG3-biocytin hepatobiliary scintigraphy can distinguish hepatitis from cholestasis in mice model and may be similarly useful in humans which differentiating the cause of neonatal jaundice in clinical study.cal study.cal study.cal study.

• Journal of Radiation Protection and Research
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• 제37권3호
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• pp.159-166
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• 2012

본 연구는 저선량율 방사선에 의한 급성독성을 조사하기 위해 BALB/c 마우스에게 낮은 선량율에 방사선을 만성 노출 후 일반증상과 체중, 장기중량, 부검소견, 혈액 및 뇨 검사를 통해 독성유무를 관찰하였다. 각각 암 수 20마리 마우스는 각 5마리씩 4군으로 분류하고, 3.49 $mGy{\cdot}h^{-1}$의 저선량율 방사선을 정상대조군, 0.02, 0.2, 2 Gy를 각각 5.7시간, 2.4일, 24일 간 지속적으로 노출시키고 조사 후 1일에 마우스를 희생하여 독성을 평가하였다. 저선량율 방사선은 최고선량의 (2 Gy) 노출에도 사망률, 임상증상, 체중, 사료와 음수 섭취량, 뇨검사, 혈청 생화학에서 독성이 관찰되지 않았다. 하지만 고환, 난소, 자궁을 포함한 생식 장기는 방사선량 의존적으로 장기의 무게가 감소되었으나, 다른 장기의 무게 변화는 관찰되지 않았다. 모든 방사선 조사군에서 혈액학적인 부작용은 관찰되지 않았고, 단지 호중구수가 노출선량에 의존적으로 증가하였다. 이번 실험결과 마우스에서 저선량율 방사선 노출은 최고 선량인 2 Gy의 노출에 다른 부작용은 관찰되지 않았으나, 암컷 수컷의 생식장기에 무게 감소가 관찰되었다.

• 대한예방한의학회지
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• 제15권1호
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• pp.37-47
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• 2011

Objectives : Previous studies have shown that Fructus mume (FM) has anti-platelet effects. The present study was performed to determine the acute oral toxicity and quality control of a crude extract of FM in ICR mice. Methods : We investigated the in vivo single dose acute toxicity of FM 95% ethanol extract. This test was orally administered once by gavage to 20 male and 20 female mice at dose levels of 0 (control group), 1250, 2500 and 5000mg/kg body weight, respectively. Mortalities, clinical findings, autopsy findings and body weight changes were monitored daily for the 14 days following the administration. HPLC analysis was performed for the simultaneous determination of ursolic acid and p-hydroxycinnamic acid in FM. Reverse-phase chromatography using a C18 column and photodiode array detection at 211 nm was used for quantification of the two maker components. The mobile phase for gradient elution consists of water and acetonitrile. Results : We observed survival rates, general toxicity, change of body weight, and autopsy. The mice did not die after single oral administration of maximum dose of FM. Autopsy of animal revealed no abnormal gross finding. Therefore, $LD_{50}$ value of FM for ICR mice was more than 5000mg/kg on oral route. The HPLC analysis showed that ursolic acid and p-hydroxycinnamic acid amounts to 9.75- and 0.12% in the extract with the retention times of 47.99- and 15.38 minutes, respectively. Conclusions : These results suggest that no toxic dose level of FM in mice is considered to be more than 5000mg/kg. Consequently, it was concluded that FM have no effect on acute toxicity and side effect in ICR mice. For the quality control of FM extract, simultaneous determination of ursolic acid and p-hydroxycinnamic acid was established.

• Nutrition Research and Practice
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• 제17권6호
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• pp.1084-1098
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• 2023

BACKGROUND/OBJECTIVES: Previous research has shown maternal betaine supplementation alleviates fetal-derived hepatic steatosis. Therefore, this study examined the anti-inflammatory effect of maternal betaine intake in offspring mice and its mechanism. MATERIALS/METHODS: Female C57BL/6J mice and their offspring were randomly divided into 3 groups according to the treatment received during gestation and lactation: control diet (CD), fatty liver disease (FLD), and fatty liver disease + 1% betaine (FLD-BET). The FLD group was given a high-fat diet and streptozotocin (HFD + STZ), and the FLD-BET group was treated with HFD + STZ + 1% betaine. After weaning, the offspring mice were given a normal diet for 5 weeks and then dissected to measure the relevant indexes. RESULTS: Compared to the CD group, the offspring mice in the FLD group revealed obvious hepatic steatosis and increased serum levels of alanine aminotransferase, interleukin (IL)-6, and tumor necrosis factor (TNF)-α; maternal betaine supplementation reversed these changes. The hepatic mRNA expression levels of IL-6, IL-18, and Caspase-1 were significantly higher in the FLD group than in the CD group. Maternal betaine supplementation reduced the expression of IL-1β, IL-6, IL-18, and apoptosis-associated speck-like protein containing C-terminal caspase recruitment domain (ASC). Maternal betaine supplementation also reversed the increasing protein expressions of nitric oxide dioxygenase-like receptor family pyrin domain containing 3 (NLRP3), ASC, Caspase-1, IL-1β, and IL-18 in offspring mice exposed to HFD + STZ. Maternal betaine supplementation decreased the homocysteine (Hcy) and s-adenosine homocysteine (SAH) levels significantly in the livers. Furthermore, the hepatic Hcy concentrations showed significant inverse relationships with the mRNA expression of TNF-α, NLRP3, ASC, and IL-18. The hepatic SAH concentration was inversely associated with the IL-1β mRNA expression. CONCLUSIONS: The lipotropic and anti-inflammatory effect of maternal betaine supplementation may be associated with the inhibition of NLRP3 inflammasome in the livers of the offspring mice.

• Radiation Oncology Journal
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• 제3권2호
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• pp.169-174
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• 1985

각 실험실마다 사용되는 동물의 종류는 매우 다양하며 특히 소동물의 경우 사용되는 동물의 선택기준은 실험의 내용은 물론 추후검사의 성적을 수식할 수 있는 요소가 펄 수 있으므로 매우 중요하다. 특히 쥐의 경우는 세계각국의 여러 실험실에서 다양한 종류에 대한 실험성적이 많이 보고되어 거의 체계화되어 있다고는 하나 같은 종류라 하더라도 사료의 종류, 환경, 사육방법 등에 따라 발육상태 및 반응이 매우 다르므로 각 실험실의 기본 정상치의 확립은 필수적인 것이다. 이에 본 영남대학병원 치료방사선과교실 소속 방사선 생물학 실험실에서는 잡종백서 731마리를 대상으로 하여 1. 분만 후 성장에 이르는 과정을 추적하여 일령에 따른 체중, 철액상을 분석하여 본 실험실에서 적당하다고 생각되는 일령 및 체중의 기본치를 정하고저 하였으며, 2. 통일한 쥐에서도 하루의 주기적인 변화에 차이가 매우 크므로 이를 분석하여 변화가 비교적 적으며 실험하기에 편리한 시간에서의 기본치를 측정하였고, 3. 위의 성적을 토대로 하여 본 병원 부속 연구소 소속 사육실에서 통일한 조건으로 사육된 암수 동수의 312마리의 쥐를 선택하여 체중, 혈액검사 및 요검사를 시행하여 이 분석결과를 본 실험실에서의 추후 실험을 위한 기본자료로 삼고저 하였다.

• 대한한의학방제학회지
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• 제21권1호
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• pp.186-199
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• 2013

Objectives : The objectives of this study was to obtain acute information (single oral dose toxicity) of Red-Koji (Monascus purpureus 12002) Fermented Scutellariae Radix Aqueous Extracts (fSR), has been traditionally used in Korean medicine for treating various diseases including inflammatory diseases. Methods : In order to observe the 50% lethal dose (LD50), approximate lethal dosage (ALD) and target organs, fSR powders were once orally administered to female and male ICR mice at dose levels of 2,000, 1,000, 500 and 0 (control) mg/kg (body weight.). The mortality and changes on body weight, clinical signs and gross observation were monitored during 14days after single oral treatment of fSR with organ weights and histopathological observations of 12 types of principle organs. Results : After single oral treatment of fSR, we could not find any mortality and toxicological evidences up to 2,000 mg/kg treated group, the limited dosages in rodents, on the body and organ weights, clinical signs, gross and histopathological observations, except for some accidental findings. Conclusions : The results obtained in this study suggest that the LD50 and ALD of fSR in both female and male mice after single oral treatment were considered as over 2,000 mg/kg because no mortalities were detected up to 2,000 mg/kg and can be safety used in clinics.

• 대한한방내과학회지
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• 제34권1호
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• pp.46-58
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• 2013

Objectives : The object of this study was to obtain acute information (single oral dose toxicity) of Scutellariae Radix Aqueous Extracts (SR; yield = 27.20%) which traditionally have been used in Korean medicine for treating various diseases including inflammatory diseases. Methods : In order to observe the 50% lethal dose ($LD_{50}$), approximate lethal dosage (ALD) and target organs, SR Aqueous Extracts were once orally administered to female and male ICR mice at dose levels of 2,000, 1,000, 500 and 0 (control) mg/kg (body weight.) 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 single oral treatment of SR according to KFDA Guidelines with organ weights and histopathological observations of 14 types of principle organs. Results : After single oral treatment of SR, we could not find any mortality and toxicological evidences up to 2,000 mg/kg treated group, the limited dosages in rodents, on the body and organ weights, clinical signs, gross and histopathological observations, except for some accidental findings. Conclusions : The results obtained in this study suggest that the $LD_{50}$ and ALD of SR in both female and male mice after single oral treatment be considered as over 2,000 mg/kg because no mortalities were detected up to 2,000 mg/kg that was the highest dose recommended by KFDA and OECD, and can be safely used in clinics.

• 대한한의학방제학회지
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• 제20권2호
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• pp.93-102
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• 2012

Objectives : Traditional medicine Gumiganghwal-tang (GT) has been used in Asia to treat inflammatory diseases including common cold, pain, fever, and algor. In this study we investigated the acute toxicity and safety of GT and fermented GT (FGT). Methods : Acute toxicity and safety were evaluated in male and female ICR mice orally administered 0 (control) and 2,000 mg/kg of GT and FGT. After the administration of GT and FGT, we observed mortality, body weight, clinical symptoms. After necropsy, organ weights were measured and blood analysis was performed. Results : There was no mortality and clinical symptoms according to the administration of GT and FGT. Comparing with control group, there were no significant alterations on the organ weight, complete blood cell count and biochemical parameters. Conclusions : Median lethal dose of GT and FGT considered to be over 2,000 mg/kg in both male and female mice, and recognized as safe with no toxicity.