• 약학회지
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• 제43권2호
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• pp.180-197
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• 1999

Acute and subacute oral toxicity of $HELIKIT^{TM}$ ($^{13}C-urea$) were carried out in Sprague-Dawley rats of both sex. The toxicity of $HELIKIT^{TM}$ was compared with urea($^{12}C-urea$ which is used for control). In acute toxicity studies, we daily examined number of deaths, clinical signs, body weights and pathological examination for 14 days after single oral administration of HELIKIT or urea($^{12}C-urea$) at a dose of 5000 mg/kg. The subacute oral toxicity was investigated in Sprague-Dawley rats treated with $HELIKIT^{TM}$ at a dose of 40, 200 and 1,000 mg/kg/day or $^{12}C-urea$ at a dose of 1,000 mg/kg/day for 4 weeks. In acute toxicity studies, $HELIKIT^{TM}$ and urea did not show any toxic effect in rats and oral LD50 value was over 5,000 mg/kg rats. In subacute toxicity studies, no death occured and no drug-related changes were found in clinical observations; body weight, food consumption, opthalmoscopy. auditory test, urinalysis, hematology, blood chemistry, gross pathological examination or organ weight between $HELIKIT^{TM}$, urea and control groups. In histopathological examinations, the slight thickening of mucosa of the limiting ridge in the stomach was noted in the animals treated with $HELIKIT^{TM}$ at a dose of 1,000 mg/kg/day and also the changes in urea group at a dose of 1,000 mg/kg/day was found, but all of these changes in the changes in ures group at a dose of 1,000 mg/kg/days was found, but all of these changes in the stomach regressed after withdrawal of the test article for 2 weeks and reversibility of the effect was revealed. These results indicate that the non toxic dose level of $HELIKIT^{TM}$ was 1,000 mg/kg/day in the 4 weeks-repeated dose study, suggesting that the substitution of $^{13}C$ for carbon in urea molecule has no effect on the toxicity of urea and changes in stomach are reversible.

• 대한약침학회지
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• 제18권3호
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• pp.42-48
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• 2015

Objectives: The aim of the study is to investigate both the single-dose intramuscular injection toxicity and the approximate lethal dose of water-soluble Carthami-flos and Cervi cornu parvum pharmacopuncture (WCFC) in male and female Sprague-Dawley (SD) rats. Methods: The study was conducted at Biotoxtech Co. according to the Good Laboratory Practice (GLP) regulation and the toxicity test guidelines of the Ministry of Food and Drug Safety (MFDS) after approval of the Institutional Animal Care and Use Committee. Dosages for the control, high dose, middle dose and low dose groups were 0.5 mL/animal of saline and 0.5, 0.25 and 0.125 mL/animal of WCFC, respectively. WCFC was injected into the muscle of the left femoral region by using a disposable syringe (1 mL, 26 gauge). The general symptoms and mortality were observed 30 minutes, 1, 2, 4, and 6 hours after the first injection and then daily for 14 days after the injection. The body weights of the SD rats were measured on the day of the injection (before injection) and on the third, seventh, and fourteenth days after the injection. Serum biochemical and hematologic tests, necropsy examinations, and histopathologic examinations at the injection site were performed after the observation period. Results: No deaths, abnormal clinical symptoms, or significant weight changes were observed in either male or female SD rats in the control or the test (0.125, 0.25, and 0.5 mL/animal) groups during the observation period. No significant differences in hematology and serum biochemistry and no macroscopic abnormalities at necropsy were found. No abnormal reactions at injection sites were noted on the topical tolerance tests. Conclusion: The results of this single-dose toxicity study show that WCFC is safe, its lethal doses in male and female SD rats being estimated to be higher than 0.5 mL/animal.

• 대한약침학회지
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• 제19권3호
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• pp.253-258
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• 2016

Objectives: The goals of this research were to evaluate acute (single-dose) and sub-acute (repeated-dose) toxicity profiles of methanolic extract of Pistacia integerrima J. L. Stewart ex Brandis (PI) for Wistar rats and to assess the safety profile of PI by observing physiological changes, mortality, changes in body weight, the histopathology of body organs, the hematology and the biochemistry of the animals. Methods: The toxicity profile of PI was evaluated using Wistar rats of both sexes. Animals were divided into four groups: Group 1; control group (normal saline), Group 2; PI-1 (250 mg/kg), Group 3; PI-2 (500 mg/kg), Group 4; PL-3 (1,000 mg/kg). An acute-toxicity study in which animals received a single dose of PI extract (2,000 mg/kg) and were then observed for 14 days for changes in skin, fur, eye color, mucous membrane secretions and excretions, gait, posture, and tonic or clonic movements was performed according to guideline 425 of the Organization of Economic and Corporation Development (OECD). In the repeated-dose toxicity study (OECD - 407) animals received a daily dose of PI extract for 28 days (4 weeks). The parameters observed in this study include body weight, hematology and biochemistry of the animals. Results: In the acute toxicity study, no mortalities or changes in behavior were noted in the animals. The repeated-dose toxicity study was also devoid of any toxicity in the animals during the 28 days of testing with PI extract. The extract did not alter- the body weight, hematology or biochemistry of the animals. The methanolic extract of PI was to be found safe to the no-observed-adverse-effect-level (NOAEL) for the single-dose and repeated-dose toxicity tests in rats. Conclusion: The methanolic extract of PI was devoid of toxicity; hence, it can be used for various ayurvedic preparations and treatments of diseases.

• Tuberculosis and Respiratory Diseases
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• 제44권5호
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• pp.1063-1071
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• 1997

연구배경 : 스테로이드제제는 기관지 천식 및 만성 폐쇄성 폐질환 환자치료에 매우 효과적으로 항염작용, 기관지내 과민반응 억제 및 기타 면역학적인 기전으로 작용한다. 그러나 부신피질 기능억제, 쿠싱 증후군, 골다공증 등의 전신적 부작용으로 인해 그 사용 범위가 제한되어 왔다. 1970년대 초반부터 고도의 국소적 작용을 갖는 흡입성 스테로이드제제가 천식 치료에 활발히 이용되고 있으나 이 약물 투여에 따른 기저 코티솔 농도에 미치는 영향에 대해서는 아직도 논란이 많다. 이에 저자들은 최근에 개발된 강력한 흡입성 스테로이드제제인 fluticasone propionate의 시상하부-뇌하수체-부 신축에 미치는 영향을 알아보고자 기관지천식과 만성 폐쇄성 폐질환 환자를 대상으로 하여, 단기간 투여용량에 따른 fluticasone propionate의 기저 코티솔 농도에 미치는 영향을 관찰하였다. 방 법 : 1993년 7월부터 1997 년 3월까지 전북대학교 병원 내과에 입원치료한 기관지 천식과 만성 폐쇄성 폐질환환자를 대상으로 하였다. 환자는 흡입성 fluticasone propionate 투여전 최소한 10일 동안 어떠한 종류의 스테로이드도 투여하지 않았고, 치료기간 12일 동안 하루에 $500{\mu}g$과 $1000{\mu}g$을 Metered Dose Inhahler(MDI) 방법으로 투여하였다. Fluticasone propionate의 투여전과 투여후 3일, 6일, 9일 및 12일째 오전 8시에 혈철 코티솔을 측정하였고, 이와 동시에 24시간 소변을 채취하여 요중 유리 코티솔 농도를측 정하였다. 결 과 : $500{\mu}g$/day 투여군에서는 투여하기 전의 혈철 및 24시간 요중 유리 코티솔 농도는 투여기간 및 투여 후와 비교시 변화를 보이지 않았다. $1000{\mu}g$/day 투여군에서는 혈철 코티솔 농도는 투여 9일 그리고 12일째 (p<0.05). 24시간 요중 유리 코티솔 농도는 투여 3일 그리고 12일째 유의있는 감소(p<0.05)를 보였으며, 전반적으로 투여전과 비교시 투여기간에 따른 혈청 및 24시간 요중 유리 코티솔 농도의 감소를 보였다. 결 론 : 이상의 결과로, 단기간 하루 $500{\mu}g$의 fluticasone propionate 투여는 내인성 코르티솔 생산에 영향을 주지 않지만, 하루 $1000{\mu}g$의 fluticasone propionate투여는 내인성 코리티솔 생산에 유의한 영향을 미치는 것으로 사료된다.

• Journal of Acupuncture Research
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• 제26권4호
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• pp.99-106
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• 2009

Objectives : The antidepressant effect of the subchronic administration of the methanolic extract of wild ginseng(WG) was investigated compared with that of cultivated ginseng(CG, panax ginseng) extract. Methods : To assess the antidepressant effect of the ginseng extracts, tail suspension test(TST) was executed in mice after daily administration of WG or CG extract for five consecutive days. Results : The WG extract at daily dose of 600mg/kg significantly reduced the total duration of immobility in the TST, whereas there was no significant reduction at daily dose of 300mg/kg WG and 600mg/kg CG. There were no individual differences between experimental groups in open field test (OFT) to evaluate psychostimulant effects of WG or CG extract. In the high performance liquid chromatography(HPLC) analysis of the extracts, it was found that WG included four times more ginsenoside Rg1 and Re, three times more Rf, and six times more Rb1 and Rc than CG. Conclusions : It is suggested that WG extract has stronger antidepressant effect than CG extract, which means it includes more antidepressant compounds than CG.

• 대한의사협회지
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• 제61권11호
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• pp.687-698
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• 2018

Inappropriate antibiotic use significantly contributes to antibiotic resistance, resulting in reduced antibiotic efficacy and an increased burden of disease. The objective of this study was to investigate the characteristics of prescribers whose antibiotics use was high and to explore factors affecting the use of antibiotics by medical institutions. This study analyzed the National Health Insurance claims data from 2015. Antibiotic prescription data were analyzed in terms of the number of defined daily doses per 1,000 patients per day, according to the World Health Organization anatomical-therapeutic-chemical classification and methodologies for measuring the defined daily dose. We investigated the characteristics of prescribers and medical institutions with high antibiotic use. Multivariate regression analyses were performed on the basis of characteristics of the medical institution (number of patients, type of medical institution [hospital or clinic], age of the physician, etc.). The number of patients and number of beds were found to be significant factors affecting antibiotic use in hospitals, and the number of patients, region, and medical department were significant factors affecting antibiotic use at the level of medical institutions. These findings are expected to help policy-makers to better target future interventions to promote prudent antibiotic prescription.

• BMB Reports
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• 제36권5호
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• pp.499-504
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• 2003

There has been increasing interest in studying the various effects of organophosphate insecticides in humans and experimental animals. Only a few data are available on the effect of the organophosphate insecticide, diazinon, on lipid metabolism. The aim of this study was to evaluate the effect of diazinon on plasma lipid constituents in mammalian animals. The plasma levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), and phospholipids (PL) were measured in albino rats that were orally treated with a single dose of diazinon at a level of $LD_{50}$ or with repeated daily doses at the levels of $\frac{1}{2}$, $\frac{1}{8}$, and $\frac{1}{32}$ $LD_{50}$ for 2, 8, and 32 days, respectively. After a 24 h post-treatment with a single $LD_{50}$ dose of diazinon, TC was not significantly changed, the HDL-C and PL levels were significantly decreased, but the LDL-C and TG levels were significantly increased. Separate daily oral administrations of diazinon at $\frac{1}{2}$ $LD_{50}$, $\frac{1}{8}$ $LD_{50}$, and $\frac{1}{32}$ $LD_{50}$ doses resulted in a significant decrease in HDL-C and PL, with no significant change in TG. The LDL-C levels were significantly increased and TC showed no significant change with $\frac{1}{2}$ $LD_{50}$ and $\frac{1}{32}$$LD_{50}$ doses of diazinon, whereas a significant decrease in the levels of TC, HDL-C, as well as LDL-C, was observed with the $\frac{1}{8}$ $LD_{50}$ dose. These data suggest that diazinon may interfere with lipid metabolism in mammals.

• 한국학교ㆍ지역보건교육학회지
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• 제18권1호
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• pp.1-12
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• 2017

Objectives: This study aimed to analyze sexual experience rates according to socio-demographic factors, health behavioral factors, and internet use time, and to identify sex experience related factors in high school students using the data from the 11th Korean Youth Health Risk Behavior Web-Based Survey. Methods: A total of 33,744 students (17,346 boys and 16,398 girls) in high schools were analyzed using the SPSS WIN version 22 program. SPSS complex samples methods were used for analyses. Socio-demographic factors, health behavioral factors, and internet use time as independents variables were included. The complex samples logistic regression analyses were used to calculate the odds ratio of the sexual experience according to the socio-demographic factors, health behavioral factors and internet use time. Unweighted frequencies and percentages were represented in result tables. Results: 3.6% of girls and 9.9% of boys in high school had sexual experiences. Daily average smoking amount and daily alcohol drinking amount were a dose-response relationship with sexual experience after considering confounding factors. Students who smoke 10-19 cigarettes had 5.74 times higher risk and 20 cigarettes or more had 7.27 times higher risk of sexual experiences, comparing with non-smoking students, relatively. Likewise, students who drink soju less than 1-2 bottles and more than 2 bottles had 3.82- and 4.35 times higher chance of sexual experiences, compared with non drinking students, respectively. Conclusions: We found that there were the dose-response relationship between health behavioral characteristics and sexual experiences. Further research is needed to identify an interaction effect between smoking and drinking alcohol on sexual experiences in high school students.

• The Korean Journal of Pain
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• 제23권3호
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• pp.179-185
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• 2010

Background: Vincristine-induced peripheral neuropathy is a major dose limiting side effect and thus effective therapeutic strategy is required. In this study, we investigated the antinociceptive effect of memantine and morphine on a vincristine-induced peripheral neuropathy model in rats. Methods: Male Sprague-Dawley rats weighing 220-240 g were used in all experiments. Rats subsequently received daily intraperitoneal injections of either vincristine sulfate (0.1 ml/kg/day) or saline (0.1 ml/kg/day) over 12 days, immediately following behavioral testing. For assessment of mechanical allodynia, mechanical stimuli using von Frey filament was applied to the paw to measure withdrawal threshold. The effects of N-methyl-D-aspartate receptors antagonist (memantine; 2.5, 5, 10 mg/kg intraperitoneal), opioid agonist (morphine; 2.5, 5, 10 mg/kg intraperitoneal) and vehicle (saline) on vicristine-induced neuropathy were evaluated. Results: Mechanical allodynia developed over the course of ten daily injections of vincristine relative to groups receiving saline at the same time. Morphine abolished the reduction in paw withdrawal threshold compared to vehicle and produced dose-responsiveness. Only the highest dose of memantine (10 mg/kg) was able to increase paw withdrawal threshold compared to vehicle. Conclusions: Systemic morphine and memantine have an antinociceptive effect on the vincristine-induced peripheral neuropathy model in rats. These results suggest morphine and memantine may be an alternative approach for the treatment of vincristine-induced peripheral neuropathic pain.

• 한국임상약학회지
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• 제28권4호
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• pp.285-292
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• 2018

Background: Long-term levodopa therapy relieves the motor dysfunction associated with Parkinson's disease (PD), but has various effects on non-motor symptoms, including cognitive dysfunction, hallucinations, and affective disorders, and can exacerbate certain aspects of dementia-like cognitive dysfunction. Here, we investigated the relationship between levodopa treatment and development of dementia in patients with PD. Methods: This retrospective study analyzed 76 consecutive patients with PD who had taken levodopa between 2011 and 2015. The participants were initially free of dementia and had initial daily levodopa doses of below 600 mg. Patients who did and did not develop comorbid dementia were compared in terms of potential predictor variables, including PD onset age, sex, levodopa doses, and non-dementia comorbidities. Results: Of the 76 patients, 21 (27.6%) developed dementia, which was followed by hallucinations and insomnia. The independent predictors of incident dementia were PD onset age and second-year and third-year average levodopa doses that were higher than the first-year average levodopa dose. Patients who developed dementia had significantly higher average daily levodopa doses and levodopa dose increases over the 6-year treatment period than those who did not develop dementia. In addition, patients with higher levodopa doses were more likely to experience hallucinations. Conclusion: These results suggest that increases in levodopa doses may be associated with a greater risk of cognitive impairment in patients with PD. Therefore, motor and cognitive functions and levodopa dose increases should be evaluated regularly during long-term levodopa therapy in patients with PD.