• Asian Pacific Journal of Cancer Prevention
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• 제13권3호
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• pp.803-807
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• 2012

For patients with neck and upper thoracic esophageal carcinoma, it is difficult to control lymph node metastases with conventional dose therapy. In this study, we assessed the feasibility of simplified intensity-modulated radiotherapy (sIMRT) and concurrent chemotherapy for 44 patients and boosted high-dose to metastatic lymph nodes. Three radiation treatment volumes were defined: PGTVnd, with which 68.1Gy was delivered in high dose group (hsIMRT group), and 60Gy in the conventional dose group (csIMRT group); PTV1, featuring 63.9Gy in the hsIMRT group and 60Gy in the csIMRT group; PTV2, with 54Gy given to both groups. The sIMRT plan included 5 equi-angular coplanar beams. All patients received the cisplatin and 5-FU regimen concurrently with radiotherapy. The treatment was completed within six weeks and one case with grade three acute bronchitis was observed in hsIMRT group. For esophageal lesions, 80% complete response (CR) and 20% partial response (PR) rates were found in the hsIMRT group, and 79.2% CR, with 20.8% PR, in the csIMRT group; for lymph node lesions, 75% CR and 25% PR rates were observed in the hsIMRT group, with 45.8% and 37.5% respectively in the csIMRT group (P<0.05). The differences in 1-, 2- and 3-year relapse-free survival rates were all statistically significant (P<0.05). The major toxicity observed in both groups was Grade I~II leucopenia. sIMRT can generate a desirable dose distribution in treatment of neck and upper thoracic esophageal carcinoma with a better short-term efficacy. Boosted high dosing to metastatic lymph nodes can increase the relapse-free survival rate.

• Fisheries and Aquatic Sciences
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• 제23권8호
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• pp.20.1-20.18
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• 2020

Background: Olive flounder, Paralichthys olivaceus, is an economically important aquaculture species in Korea. Olive flounders have been heavily damaged by streptococcal infections every year and are treated with antibiotics. However, antibiotic abuse is causing the emergence of resistant strains, and to overcome this, research has shown that new antibiotics must be applied. Tylosin is a relatively safe antibiotic and has good activity against Gram-positive bacteria and mycoplasma. We studied the therapeutic effects and side effects of tylosin on Streptococcus parauberis-infected olive flounder. Methods: After artificial infection of olive flounder with S. parauberis SPOF18J3, an appropriate dose of tylosin was confirmed by intramuscular injection (I.M.) at 2.5, 5, 10, and 15 mg/kg, and oral administration at 10 and 20 mg/kg. After I.M. and oral administration dosing of tylosin, side effects were confirmed by serological analysis, histopathological analysis, and median lethal dose (LD₅₀) analysis at both an appropriate concentration and a high concentration. Statistical analysis was performed using one-way analysis of variance (ANOVA) and Tukey's test (p < 0.05). Results: The appropriate I.M. and oral administration concentration of tylosin administered to olive flounder infected with S. parauberis SPOF18J3 was found to be 10 mg/kg. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were showed not significantly different between the control group and the experimental groups. The histopathologic results showed mild inflammatory responses in muscle and tubular vacuolization and tubular atrophy appeared, but there were no significant differences between the groups. The LD₅₀ was confirmed to be 461 mg/kg. Conclusion: In this study, an effective treatment method was provided by verifying the treatment effects and side effects of tylosin in olive flounder infected with S. parauberis, which can be applied directly to aquaculture sites. In addition, these results may be used as a reference for evaluation required upon request to obtain approval for tylosin antibiotics as fishery antibiotics in Korea. After approval, it is possible that a fishery disease manager will be able to prescribe and sell the antibiotic tylosin.

• 대한환경공학회지
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• 제29권6호
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• pp.699-705
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• 2007

본 연구에서는, 안산정수장에 구축된 수도시설 운영정보화 시스템에 의한 처리수질개선 등 정수장 효율개선효과를 평가하였다. 분석기간 동안의 안산정수장 생활용수 유입유량은 운영정보화 시스템이 구축되기 전인 2004년도보다 구축 후인 2005년도가 약 15.6% 감소한 것으로 나타났다. 원수의 평균탁도는 2005년 12.37 NTU, 2004년 12.06 NTU로 비슷한 값을 나타내었으나, 연평균 응집제의 주입농도는 2005년도가 12.06 mg/L으로 2004년(10.31 mg/L)보다 다소 높은 것으로 나타났고, 정수탁도는 약간 개선된 처리효율을 나타내었다. 원수의 $COD_{Mn}$ 및 BOD 등의 분석결과, 2004년보다 2005년의 원수수질이 개선된 것으로 판단할 수 있었다. 정수의 $KMnO_4$ 소비량은 2004년(2.95 mg/L)보다 2005년은 1.25 mg/L로써 그 양이 줄어들었고, THMs의 농도도 2004년(0.038 mg/L)보다 2005년 0.025 mg/L로써 다소 개선되었다. 본 연구결과, 약품주입 등 정수장 운영은 운영 정보화 시스템의 구축에 의해 보다 최적의 상태를 도모할 수 있으며, 이에 따라 수질개선효과도 있음을 판단할 수 있었다.

• 한국산학기술학회논문지
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• 제9권2호
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• pp.493-499
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• 2008

본 연구는 가정 옥내급수관에 적수 및 탁수 등을 유발하고 철, 구리 등 중금속이 용출될 수 있는 부식 문제 해결을 위해 인산염계 부식억제제를 주입하는 회분식 실험을 통해 옥내급수관으로 가장 많이 사용되고 있는 아연도 강관의 표면 도금이 벗겨진 상태인 탄소강관을 대상으로 주요 수질인자의 변화, 철의 용출농도 변화, 부식도 및 부착도 평가, 시편의 상태를 고찰하였다. 탄소강관에서 부식억제제를 주입하였을때 pH, 전기전도도, 알칼리도, Ca-경도 등의 부식성 수질인자는 약간의 변화가 있었으나, 큰 영향은 없었다. 탁도의 경우 부식억제제를 5 mg $P_2O_5/L$ 주입시 주입하지 않은 것에 비해 약 10배정도 낮게 나타나 부식억제제가 탁도 유발 억제에 큰 효과가 있음을 확인하였다. 부식억제제의 주입농도가 5 mg $P_2O_5/L$일 때까지는 부식억제제 농도가 증가함에 따라 철(Fe) 용출농도와 부식도가 서서히 감소하는 경향을 보였으며, 부식억제제 5 mg $P_2O_5/L$ 주입시 급격히 감소하여 부식억제제를 주입하지 않은 경우보다 각각 약 12.2배, 약 24배의 저감 효과를 보였다. 결론적으로 인산염계 부식억제제 약 5 mg $P_2O_5/L$ 주입은 옥내 급수관 내부 표면에 치밀한 방식 피막을 형성하여 부식제어에 효과가 있을 것으로 판단된다.

• Toxicological Research
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• 제8권2호
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• pp.217-233
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• 1992

This study was performed to determine the toxic effects of graded dose levels of SKI 2053R after repeated administration. Three groups of Sprague-Dawley rats(10M and 10F per group) were given a total of 25 i.v. injections of SKI 2053R (1.50,3.75,9.38mg/kg/day). In order to compare the toxic effects of SKI 2053R with those of cisplatin, one group of Sprague-Dawley rats (10M and 10F per group) were given a total of 25 i.v.injections of cisplatin (1.70mg/kg/day). The dosing schedule was divided into five courses of 5 consecutive days with 16-day dose-free intervals between each course. No drug-related toxicity occurred in low dose level group (1.50mg/kg/day) of SKI2053R. From the results of hematological examination, peripheral WBC counts, RBC counts and hemoglobin of high dose level group(9.38mg/kg/day)of SKI 2053R were significantly lower than those of no-treated group. Other toxicities including reduced final body weight, proteinuria and hematuria were observed in high dose level group of SKI 2053R. But, no change was detected in serum biochemical values of SKI 2053R treated groups. All of the rats in cisplatin treated group were died between 3 and 13 weeks, while rats treated with SKI2053R survived to the end except one rat of middle dose level group(3.75mg/kg/day). In histopathological examinations, rats that received cisplatin manifested severe tubular damage in kidney and hemosiderosis in spleen, but no critical pathological lesion was observed in rats of other groups. Considering the results of this study, it was concluded that non-toxic dose of SKI 2053R in this treatment schedule was estimated to be 3.75 mg/kg/day and the maximum tolerated dose was to be higher than 9.38mg/kg/day. The toxic profiles fo SKI 2053R were different from those of cisplatin, and its toxicity was considerably lower than that of cisplatin.

• Toxicological Research
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• 제8권2호
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• pp.235-253
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• 1992

A subacute toxicity study of cis-Malonato[(4R,5R)-4,5-bis(aminomethyl)-2-isopropyl-1,3-dioxolane]platinum(II)(SKI 2053R) was carried out to obtain information on its toxicological profiles, and to determine the maximum tolerated dose in beagle dogs. Four groups of beagle dogs (2M and 2F per group, 0,0.5,1.0,2.0mg/kg/day)were given 15 i.v. injections of SKI 2053R. In order to compare the toxic effects of SKI 2053R with those of cisplatin, one group was treated with cisplatin(0.7mg/kg/day)according to the same treatment schedule. The dosing schedule was divided into 3 courses of 5 consecutive days with 23-day dose-free intervals between each course. After completion of the treatments, remaining dogs were necropsied under established guidelines. Three of four dogs in the high dose group and one of four dogs in the middle dose group treated with SKI 2053R died of hypovolemic shock secondary to hemorrhagic and ulcerative enterocolitis. No toxicity-related mortality occurred in the low dose group of SKI 2053R. No survivor was observed in the group of cisplatin. Clinical signs including vomiting, diarrhea, anorexia and loss body weight were apparent in dogs given either cisplatin or high and middle doses of SKI 2053R. Severe thrombocytopenia and leukocytopenia were observed in the high dose group of SKI 2053R and cisplatin-treatment group, while toxicities as bone marrow suppression were reversible. The significant elevation of serum ALP values in group of SKI 2053R(2.0 mg/kg/day and 1.0mg/kg/day) and cisplatin(0.7mg/kg/day)was observed. Slight proteinuria waa observed in high and middle dose level groups of SKI 2053R. In histopathological examinations, pathological alterations of liver, kidney and spleen were noted dose-dependantly in dogs treated with SKI 2053R, and there was no overt sign of toxicity in low dose group of SKI 2053R. Compared to SKI 2053R, more severe durg-related toxicities occurred in dogs treated with cisplatin. It waw estimated that maximum tolerated dose of SKI 2053R in this treatment schedule was 0.5~0.7mg/kg/day. In conclusion, overall toxic potential of SKI 2053R was approximately 3 times lower than that of cisplatin with respect of lethality.

• Biomolecules & Therapeutics
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• 제20권2호
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• pp.226-233
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• 2012

Ethanol exposure during gestational period is related to growth retardation, morphological abnormality, and even in neurological abnormalities including attention deficit/hyperactivity disorder (ADHD)-like behaviors on offspring. However, relatively little is known about the effects of maternal ethanol consumption prior to conception on their offspring. In this study, we investigated whether maternal ethanol administration during preconceptional phase produces ADHD-like behaviors in the rat offspring. Sprague-Dawley (SD) female rats were administrated ethanol via intragastric intubation with dosing regimen of 6 g/kg daily for 10 consecutive days and treated female rats then mated with non-treated male SD rats after 8 weeks. Another group subjected to the same procedure as those conducted on ethanol treated group except the saline administration instead of ethanol. Offspring was tested for their ADHD-like behaviors using open field test, Y maze test and impulsivity test that is performed in the aversive electronic foot shock paradigm. Offspring of preconceptional ethanol treated (EtOH) group showed hyperlocomotive activity, attention deficit and impulsivity. And reduction of striatal dopamine transporter (DAT) level was observed by Western blot in the EtOH group, compared to control (Con) group, while the immunohistochemical analysis exhibited increased expression of norepinephrine transporter (NET) in the frontal cortex. These results suggest that maternal ethanol consumption in the preconceptional phase induces ADHD-like behaviors in offspring that might be related to the abnormal expression of DAT and NET in rat.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 2008년도 Proceedings of the Convention
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• pp.5-20
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• 2008

GLP 1 기반의 약(GLP-1 유도체와 DPP IV 저해제)과 인크레틴 유사체는 최근 가장 각광을 받는 2당뇨 치료제 계열 중 하나이다. GLP-1은 위장에서 분비되는 핍타이드 인크레틴 호르몬으로서 췌장으로부터의 당-의존적 인슐린 분비를 증진하고, 위장통과를 지연시키며, 췌장 베타세포의 증식을 촉진한다. DPP IV 저해제는 GLP-1 불활성화시키는 DPP IV 효소의 활성을 저해함으로써 인크레틴처럼 작용한다. LC15-0133은 경쟁적, 가역적 DPP IV 저해제 ($IC_{50}$ = 24 nM, Ki=0.247 nM)이며, DPP II, DPP 8, 엘라스타제, 트릴신, 유로키나제에 비해 DPPIV 에 대한 선택적 억제 효능이 우수하다. LC15-0133 랫과 개에서 긴 반감기와, 우수한 경구흡수율을 보였다. LC15-0133 랫과 개에서 각각 0.1 mg/kg 0.02 mg/kg 용량으로 경구투여하고 24시간이 지난 후에도 50%이상의 혈장 DPP IV 활성 억제효능을 유지하였다. C57BL/6 마우스에서 LC15-013301 경구당부하에 의한 혈당증가를 억제하는 최소유효용량은 0.01 mg/kg, 당에 의한 GLP-1 분비를 증가시키는 최소유효용량은 0.1 mg/kg 이다. Zucker 당뇨 랫에서 LC15-01331의 1개월간의 경구반복투여는 당뇨병으로의 진행을 지연시키고, 혈중 HbA1c 감소시켰다. 결론적으로, LC15-0133은 신규의 강력하고, 선택적인 경구 DPP IV 저해제이며, 여러가지 동물모델에서 탁월한 혈당강하효능을 보였다.

• 한국식품위생안전성학회지
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• 제5권1호
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• pp.7-12
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• 1990

Radiolabeled Brazilin(^3H-Brazilin)을 웅성 Wistar Rats에 투여하여 plasma concentration-time profile, urine 및 bile로의 배설, 조직분포 및 plasma protein에 대한 결합률을 살펴보았다. 1. Pharmacokinetic parameters는 다음과 같았다. $t_{1/2}$은 13.7 hr, AUC는 $\53.38\;\mu\textrm{g}{\cdot}hr/ml$, AUMC는 $1013.4\;\mu\textrm{g}{\cdot}hr^2/ml$ MRT는 18.95hr, Vss 17.778l/kg 그리고 CL은 936.77ml/hr.kg였다. 2. Plasma concentration-time profile에서 enterohepaic circulation을 시사하여 2nd peak가 발견되었고. 담즙배설 실험으로 확증할 수가 있었다. 결구투여 후 담즙 배설은 투여량의 64.4%가 10시간에 걸쳐 배설되었고, 3시간째 그 배설속도는 maximum을 이뤘다. 3. Vss는 17.8 l/kg으로 큰 값을 나타냈고, 따라서 뇌를 제외한 대부분의 조직에 Brazilin은 분포하였고 특히 liver와 kidney, epididymus 그리고 testis에 고농도 분포함을 알 수 있었다. 4. 경구투여량의 44.1%가 , 정맥주사 후 투여량의 62.9%가 urine을 통해 배설되었다. Urine을 통해 배설되는 양의 대부분(80%)은 24시간 내에 배설되었다. 5. Plasma protein에 대한 결합율을 한외여과법으로 측정한 결과 $40{\pm}4%$가 결합하는 것으로 나타났다.

• 생명과학회지
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• 제27권2호
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• pp.194-201
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• 2017

유채는 십자화과로 분류되는 유지작물로써 전 세계적으로 재배되는 작물이다. 이전 연구결과에서 가뭄저항성을 증대시키는 것으로 보고된 애기장대의 ${\beta}$-glucosidase 1 (AtBG1) 유전자를 도입함으로써 가뭄저항성 형질전환 유채를 개발하였다. 새로 개발된 형질전환 작물들은 그 이용에 대한 안전성에 대하여 어떠한 정보도 제공되지 않기 때문에 작물의 안정성에 대한 증명이 필수적이다. 이러한 안정성 평가는 작물의 역사적 사용과 과학적 증거를 기초로 한다. 이번 연구에서는 AtBG1이 도입된 형질전환 유채의 급성투여독성시험을 통하여 암수 마우스 각각에서 한계투여 용량을 확인하는 것을 목적으로 하였다. 이를 위해 OECD의 급성독성의 권고안에 따라 AtBG1 단백질을 암수 각각 5마리의 ICR 마우스에 몸무게 1 kg 당 2,000 mg을 부형제에 녹여 강제구강투여 하였다. 투여일부터 14일 동안 운동성, 병리학적 이상, 몸무게를 측정하였고 마지막 14일에는 안락사 후에 부검을 통해 AtBG1 투여군과 비투여군의 차이를 확인하였다. 이상의 실험을 통하여 AtBG1 단백질이 운동성, 병리학적 이상, 몸무게 및 부검 결과에서 대조구와 실험구, 두 그룹간의 특이적인 차이를 보이지 않음을 확인하였다. 또한 AtBG1 단백질은 급성독성의 측면에서 안전한 물질로 판단되며, 한계허용치 용량이 2,000 mg을 상회함을 확인하였다. 따라서, 이는 차후 AtBG1 도입 유채의 인체위해성 평가 자료로 사용될 수 있을 것으로 사료된다.