• Toxicological Research
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• 제19권3호
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• pp.217-225
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• 2003

Changes of plasma DNA contents and serum biochemical values were measured in rats administered with lead acetate to investigate the in vivo cytotoxic effects of lead and examine the usefulness of these in vivo cytotoxicity changes as indicators of lead exposure and diagnosis of lead poisoning. Rats were given once intraperitonealy with lead acetate (1.6, 8, 40 and 200 mg/kg b.w) and the changes of plasma DNA contents and serum biochemical values were measured at the time of 2, 4, 8, 24, 48 and 72 hours after the administration of lead acetate. Plasma DNA contents began to increase at 2 hours after the administration of lead acetate in the treatment groups of 8, 40 and 200 mg/kg b.w dose-dependently and significantly compared with control group. These DNA increases of each dosage group were continued until 24, 48 and 72 hours and the maximum levels of DNA (4.02, 10.67 and 14.10 times of control) were arrived at 8, 8 and 4 hours after the each treatment, respectively. Among 10 serum biochemical indicators, the activities of creatine kinase were increased to maximum level (6.55 times of control) at 2 hours after the administration and remained to be significantly higher than that of control by 8 hours in the treatment group of 200 mg, however, after 48 hours, the levels in the treatment groups of 40 mg above were lower than that of control. The values of aspartate aminotransferase, alanine aminotransferase and lactate dehydrogenase were higher than that of control from 2 to 24 hours in the treatment group of 200 mg. Maximum levels of these enzymes were 3.34, 3.00 and 3.19 times of control, respectively. Both of alkaline phosphatase and triglyceride values in the treatment groups were decreased compared with control. In the case of alka-line phosphatse, the values were significanly decreased from 24 hours and more severely decreased until 72 hours in the treatment groups of 40 mg above (p<0.01). The minimum value was 0.36 times of control in the 200 mg group. The values of triglyceride were significantly decreased in the tratment groups of 40 mg above (p<0.01), but the values were not different significantly among the treatment groups. This study demonstrates that plasma DNA content and serum biochemical values such as aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, alkaline phosphatase and triglyceride are valuable as biomarkers for exposure assessment and diagnosis of lead poisoning.

• Mycobiology
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• 제40권2호
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• pp.117-123
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• 2012

Nuruk contributes to the unique characteristics of Korean alcoholic beverages. In this study, the effects of nuruk extracts (NE) on anti-oxidant characters, melanogenesis, and anti-photoaging activity were investigated. NEs were obtained from the 70% ethanol extracts of six types of nuruk, which have been used in brewing of fermented alcohol beverages in Korea. First, various antioxidant characteristics were identified in terms of 2,2'-azino-bis(3-ethylbenzthiozoline-6-sulphonic acid) (ABTS) radical scavenging activity, superoxide dismutase (SOD) expression, and inhibition of xanthine oxidase activity. NE#4 exhibited potent ABTS radical scavenging activity ($IC_{50}$ = 19.51 ${\mu}g$/mL). Compared with NE#4, relatively lower levels of activity were observed for NE#3 and NE#6, with $IC_{50}$ values of 90.99 and 76.88 ${\mu}g$/mL, respectively. According to results of western blot analysis for determination of SOD expression in $H_2O_2$-treated HepG2 cells, NE#5 and NE#6 induced a dramatic increase in the expression ratio of SOD, compared to the group treated with $H_2O_2$ only. Activity of xanthine oxidase, which converts xanthine into uric acid, generating superoxide ions, was inhibited by NE#4 and NE#6 in a dose-dependent manner. NE#4 induced significant inhibition of mushroom tyrosinase activity. A reduction in cellular melanin contents of 80% was observed in B16F1 melanocytes treated with NE#5 and NE#6; these effects were similar to those of arbutin at 100 ${\mu}M$. In addition, gelatin zymography and reverse transcription-PCR analysis were performed for assessment of anti-photoaging activity of Nuruk. Treatment with NE#6 resulted in dramatically inhibited activities of matrix metalloproteinase (MMP)-2/-9, suppressed expression of MMP-1, and increased expression of type-1 procollagen. Results of gelatin zymography for NE#4 and NE#5 were similar, to a slightly lesser degree. These results suggest the potential of NE#4 and NE#6 as natural ingredients for use in functional foods and cosmetics.

• Asian Pacific Journal of Cancer Prevention
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• 제15권9호
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• pp.3939-3944
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• 2014

Background: To elucidate the role of rapamycin and PF4 on apoptosis regulation via Bax (pro-apoptosis), Bcl-2 (anti-apoptosis) and survivin activation on the growth in the 1-methyl-1-nitrosourea-induced invasive breast carcinoma model. Materials and Methods: Thirty five female Sprague Dawley rats at age 21-day old were divided into 4 groups; Group 1 (control, n=10), Group 2 (PF4, n=5), Group 3 (rapamycin, n=10) and Group 4 (rapamycin+PF4, n=10). MNU was administered intraperitionally, dosed at 70mg/kg body weight. The rats were treated when the tumors reached the size of $14.5{\pm}0.5mm$ and subsequently sacrificed after 5 days. Rapamycin and PF4 were administered as focal intralesional injections at the dose of $20{\mu}g$/lesion. The tumor tissue was then subjected to histopathological examinations for morphological appraisal and immunohistochemical assessment of the pro-apoptotic marker, Bax and anti-apoptotic markers, Bcl-2 and survivin. Results: The histopathological pattern of the untreated control cohort showed that the severity of the malignancy augments with mammary tumor growth. Tumors developing in untreated groups were more aggressive whilst those in treated groups demonstrated a transformation to a less aggressive subtype. Combined treatment resulted in a significant reduction of tumor size without phenotypic changes. Bax, the pro-apoptotic marker, was significantly expressed at higher levels in the rapamycin-treated and rapamycin+PF4-treated groups compared to controls (p<0.05). Consequently, survivin was also significantly downregulated in the rapamycin-treated and rapamycin+PF4-treated group and this was significantly different when compared to controls (p). Conclusions: In our rat model, it could be clearly shown that rapamycin specifically affects Bax and survivin signaling pathways in activation of apoptosis. We conclude that rapamycin plays a critical role in the induction of apoptosis in MNU-induced mammary carcinoma.

• 한국임상수의학회지
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• 제31권3호
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• pp.199-205
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• 2014

쉽게 발효되는 탄수화물의 과도한 양의 섭취에 따른 급성 또는 만성의 산증은 방글라데시에서 염소의 생산성 문제로 나타나고 있다. 본 연구는 유산증의 분포와 다른 치료제간의 반응을 조사하였다. 본 연구를 위해, 야외 지역 동물 병원, Faridpur, Bangladseh에서 조사 한 1,128마리의 염소가 검사 되었으며, 그 중 40마리의 염소(3.55%의 분포율)가 유산증에 대해 양성으로 확인되었다. 토종 염소 (2.7%)에서는 3 년 이상된 연령(4.64%)의 암컷 (4.64%)에서 가장 높은 발병을 보였다. 40마리 염소의 치료 평가를 위해서 염소는 그룹당 10마리씩 4개의 그룹 A, B, C와 D로 분류 하였다. 그룹A는 경구, 8% 수산화 마그네슘(v/w)을 체중 1 g/kg으로 경구 투여 하였다. 그룹 B에서는 그룹 A와 같은 량의 8% 수산화 마그네슘에 더하여 체중 0.9 ml/kg 비율로 7.5%의 중탄산 나트륨을 정맥 내 투여 하였다. 그룹 D에서 염소는 생강, nuxvomica, 탄산나트륨, 황산 코발트, 분말 형태의 황산제1철 과 티아민 질산염의 혼합물을 1 g/kg 체중의 비율로 경구 투여하였다. 그룹 C의 염소는 그룹 A, B와 D의 조합 약물로 치료하였다. 각 그룹은 치료 전후에 직장 온도, 맥박수, 호흡 수를 검사하였다. 평균 $21{\pm}1.8$ 시간으로 그룹 C가 가장 높은 회복률을 보였다. 결론적으로 유산증은 염소에서 흔한 질병이며 치료효과는 약물의 조합을 통해서 효과적으로 증상을 감소 시킬 수 있었다.

• 방사성폐기물학회지
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• 제18권2_spc호
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• pp.291-303
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• 2020

영구정지후 해체가 계획된 고리 1호기 원자력발전소는 해체과정에서 다양한 종류의 방사성폐기물이 대량으로 발생될 것으로 예상되고 있으며, 이 중 원자로 및 내부구조물은 방사능 수치가 높으므로 1차측에서 적절한 크기와 중량으로 해체된다. 고리 1호기 해체시 원자로 및 내부구조물에서 발생되는 방사성폐기물에 대하여 기존 폐기물의 자체처분 현황 및 법적 제한 사항 분석 등을 통해 적절하고 효율적인 처분방법을 마련하는 것은 중요한 사안일 것으로 판단된다. 원자로 및 내부구조물에서 발생되는 폐기물은 중준위에서부터 자체처분까지 다양한 준위의 폐기물들이 발생되며, 이 중 자체처분 준위에 해당되는 폐기물은 방사화 평가 결과, 원자로 상부 헤드와 상부 헤드 인슐레이션에서 발생되는 것으로 나타났다. 본 논문에서는 방사화 평가 결과를 바탕으로 자체처분 준위에 해당되는 폐기물을 자체처분 평가 코드인 RESRAD-RECYCLE 코드를 사용하여 자체처분 안전성 평가를 수행하였다. 대상 폐기물의 자체처분 시나리오를 선정하고 자체처분시 개인 및 집단별 최대선량을 계산하여 국내 원자력안전법에서 규정하는 자체처분 기준 제한치의 만족 여부를 판단하였다. 평가 결과, 전체적으로 상당히 낮은 결과값을 보이며 기준 제한치를 만족하는 결과를 나타내었으며, 핵종별 자체처분 허용농도를 도출하였다.

• IMMUNE NETWORK
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• 제3권1호
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• pp.38-46
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• 2003

Background: Platelet-activating factor (PAF) induces nuclear factor $(NF)-{\kappa}B$ activation and angiogenesis and increases tumor growth and pulmonary tumor metastasis in vivo. The role of $NF-{\kappa}B$ activation in PAF-induced angiogenesis in a mouse model of Matrigel implantation, and in PAF-mediated pulmonary tumor metastasis were investigated. Methods: Angiogenesis using Matrigel and experimental pulmonary tumor metastasis were tested in a mouse model. Electrophoretic mobility shift assay was done for the assessment of $NF-{\kappa}B$ translocation to the nucleus. Expression of angiogenic factors, such as tumor necrosis factor $(TNF)-{\alpha}$, interleukin $(IL)-1{\alpha}$, basic fibroblast growth factor (bFGF), and vascular endothelial growth factor (VEGF) were tested by RT-PCR and ELISA. Results: PAF induced a dose- and time-dependent angiogenic response. PAF-induced angiogenesis was significantly blocked by PAF antagonist, CV6209, and inhibitors of $NF-{\kappa}B$ expression or action, including antisense oligonucleotides to p65 subunit of $NF-{\kappa}B$ (p65 AS) and antioxidants such as ${\alpha}$-tocopherol and N-acetyl-L-cysteine. In vitro, PAF activated the transcription factor, $NF-{\kappa}B$ and induced mRNA expression of $TNF-{\alpha}$, $IL-1{\alpha}$, bFGF, VEGF, and its receptor, KDR. The PAF-induced expression of the above mentioned factors was inhibited by p65 AS or antioxidants. Also, protein synthesis of VEGF was increased by PAF and inhibited by p65 AS or antioxidants. The angiogenic effect of PAF was blocked when anti-VEGF antibodies was treated or antibodies against $TNF-{\alpha}$, $IL-1{\alpha}$, and bFGF was co-administrated, but not by antibodies against $TNF-{\alpha}$, $IL-1{\alpha}$, and bFGF each alone. PAF-augmented pulmonary tumor metastasis was inhibited by p65 AS or antioxidants. Conclusion: These data indicate that PAF increases angiogenesis and pulmonary tumor metastasis through $NF-{\kappa}B$ activation and expression of $NF-{\kappa}B$-dependent angiogenic factors.

• 대한핵의학회지
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• 제8권1_2호
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• pp.29-37
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• 1974

The $^{99m}Tc$-pertechnetate thyroid uptake rates(20 min) were measured in 24 healthy normal subjects, 140 patients with nontoxic goiter and 98 patients with thyrotoxicosis who were treated at the Thyroid Clinic, Seoul National University Hospital, from August 1972 to August 1973. Diagnostic reliabilities and correlations between $^{99m}TcO_4$-thyroid uptake rate (20 min) and other thyroid function tests were evaluated. The observed results were as follows 1. The $^{99m}TcO_4$-thyroid uptake rates (20 min) in normal subjects, euthyroid group and hyperthyroid group were $4.1{\pm}0.9%,\;5.2{\pm}1.8%\;and\;29.7{\pm}10.6%$. There was a significant difference between the mean of the euthyroid group and the mean of the hyperthyroid group and so differentiation between them can be easy. 2. In the diagnosis of hyperthyroidism, the reliabilities of $^{99m}TcO_4$- thyroid uptake rate(20 min), $^{131}I$ thyroid uptake rate(24hrs), serum $T_3$ resin uptake rate, serum $T_4\;and\;T_7\;were\;87.9{\sim}97.9%,\;81.2{\sim}94.4%,\;87.9{\sim}97.9%,\;90.5{\sim}99.3%\;and\;93.7{\sim}100%$. $^{99m}TcO_4$-thyroid uptake rate(20 min) is more accurate than $^{131}I$ thyroid uptake rate (24 hrs) in the diagnosis of hyperthyroidism. 3. $^{99m}TcO_4$-thyroid uptake rate (20 min) was well correlated with $^{131}I$ thyroid uptake rate (24 hrs), serum $T_3$ resin uptake rate, serum $T_4\;and\;T_7$. Points in favor of $^{99m}Tc$ are that it gives a small radiation dose to the thyroid, that tests can be repeated at the short interval, the study can be completed at a single patient visit and it is particularly well suited for the assessment of thyroid function in patients being treated with an antithyroid drug.

• 한국식품과학회지
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• 제52권5호
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• pp.555-559
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• 2020

본 연구에서는 팔라티노스 시럽 Pal-L을 반복 투여하였을 때 나타나는 독성을 확인하기 위하여 암수 SD rat에 1,000 mg/kg의 용량으로 14일간 1일 1회 경구 투여한 후 사망률, 일반 증상, 체중 및 사료/음수 섭취량 변화, 장기 중량의 변화, 혈액 및 혈액 생화학적 변화, 뇨 분석 및 간과 신장의 조직학적 검사에 대한 변화를 관찰하였다. 실험 결과 투여 기간 중 암수 대조군 및 Pal-L을 투여한 군 모두 사망 동물은 발견되지 않았으며, 팔라티노스의 반복 투여에 의한 일반 증상의 변화 역시 관찰되지 않았다. 또한 체중 및 사료/음수 섭취량에 대한 변화, 장기 중량의 변화에 대한 이상 변화 역시 관찰되지 않았다. 부검 후 채취한 전혈의 혈액학적 분석 결과, 암컷 Pal-L 투여군에서 Hgb, MCHC, PLT의 수치가 유의적인 차이를 보였으나 정상 범위 내에서의 차이로 팔라티노스에 의한 독성이라고 판단하기는 어려웠으며, 혈액의 생화학적 분석 결과 암수 대조군 및 시험군에서 모든 항목이 정상 수치를 나타냈다. 부검 전 채취한 뇨를 분석한 결과 암컷 시험군에서 glucose, 수컷 시험군에서 total protein 수치가 유의적으로 감소하였지만 정상 범위 내에서의 차이로 팔라티노스에 의한 독성이라고 판단하기 또한 어려웠다. 혈액, 혈청 및 뇨에서 일부 유의적인 차이가 나타난 것을 바탕으로 간 및 신장에 대한 조직병리학적 검사를 진행한 결과 대조군과 시험군 모두 조직학적 이상은 관찰되지 않았다. 이상의 결과를 종합해보면 SD rat을 이용하여 팔라티노스(Palatinose-L)를 1,000 mg/kg/day의 용량으로 14일간 반복 경구투여하고 사망 여부, 체중 변화, 혈액학적 검사, 혈액 생화학적 검사, 뇨 분석 및 조직학적 검사 등을 통해 독성 평가를 진행하고자 하였다. 그 결과 2주간의 투여 기간 동안 시험 동물에게 어떠한 독성도 관찰되지 않았음을 확인하였고, 이에 따라 팔라티노스(Pal-L)는 1,000 mg/kg/day 용량까지는 독성이 없는 안전한 물질이라는 것이 최종 확인되었다.

• 생물정신의학
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• 제2권1호
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• pp.131-139
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• 1995

Clozapine은 정형적 항정신병약물에 반응하지 않는 불응성 정신분열증 환자에게 효과적이며, 추체외로부작용이 적은 비정형적 향정신병약물로 보고되고있다. 따라서 저자들은 불응성 정신분열증환자를 대상으로 clozapine의 항정신병효과 및 부좌용에 대해 대표적 전형적 항정신병약물인 haloperidol과 비교연구하였다. 대상환자를 clozapine투여군(17명) 과 haloperidol 투여군 (16명)으로 나누어 12주 동안 각각의 약물을 투여하는 전향적 개방대조연구를 하였다. 두가지 약물의 치료효과와 부작용은 BPRS, PANSS, Simpson-Angus Rating Scale 및 Adverse Events-Somatic Symptoms를 사용하여 평가하였다. 약물투여 12주후 clozapine투여군이 76.5% 에서 치료반응을 보인데 비해 haloperidol투여군은 31.2%의 치료반응을 보임으로써 두약물 투여군간에 유의한 차이가 있었다. BPRS와 PANSS 척도상 clozapine투여군이 haloperidol투여군에 비하여 BPRS, PANSS 양성증상 및 일반증상 척도는 약물투여 8주후부터, PANSS 음성척도는 약물투여 4주후부터 12주까지 일관성있게 지속적으로 의미있는 호전을 보였다. Clozapine투여군에서는 타액분비(70.6%), 졸리움(52.9%), 변비(29.4%) 및 저혈압(23.4%)이, haloperidol투여군은 진전(37.5%), 정좌불능(25.0%), 강직(18.8%) 및 무운동(18.8%)이 흔히 보고되었다. 하지만 두약물 투여군 모두에서 대부분 경미하고 환자가 견딜 정도였다. Clozapine투여군에서 약물투여 전에 비해서 약물투여 12주후 백혈구와 호중구의 유의한 변화는 없었다. 이상의 결과를 종합해볼 때, clozapine은 정형적 항정신병약물에 치료효과가 없거나 추체외로부작용 때문에 약물투여가 어려운 경우의 한국인 불응성 정신분열증환자에게 효과적인 비정형적 항정신병약물이다.

• 대한한방내과학회지
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• 제27권1호
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• pp.188-196
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• 2006

Background: Ma-huang (Ephedra sinica) has been widely used to treat respiratory disease in oriental medicine for over a hundred years. Ma-huang preparations contain approximately 1.25% ephedrine alkaloids. Recently, the ephedra alkaloids have received much press lately due to adverse effects in those using whole extracts as 'dietary supplements' for weight loss or athletic performance enhancement, and these reports are troubling given the increasing use of Ma-huang by the general public. The purpose of this report is to determine the proper dosage to minimize adverse effects and maximize the potential curative value. Objectives : The object of this study was to find an effective yet low risk dosage of Ma-huang. Methods : The study was designed as a double-blind randomized placebo-controlled trial. The subjects of this study were 26 adults between 20 to 40 of age who agreed to participate in this study. They were allocated through randomization into three groups. Each group took three opaque capsules three times a day. A group (N=9) took one Ma-huang capsule and two placebo capsules, B group (N=8) took two Ma-huang capsules and one placebo capsule, C group (N=9) took three Ma-huang capsules. The total trial periods was two days. To compare the adverse effects of Ma-huang according to dosage, blood pressure and pulse were checked, and other adverse effects were assessed using a morning questionnaire, patient's global assessment scale and Wong-Baker faces pain rating. Results : The following result were obtained: 1. After taking 18 g of Ma-huang per day, pulse rate had a significant increase. 2. After taking more than 6 g of Ma-huang per day, palpitation would be increased significantly. 3. After taking more than 18 g of Ma-huang per day, tiredness would be increased significantly. Conclusion: According to the results, 12 g of Ma-huang per day will minimize adverse effects and maximize the potential curative value.