• International Journal of Control, Automation, and Systems
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• 제1권3호
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• pp.282-288
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• 2003

It is known that HIV (Human Immunodeficiency Virus) infection, which causes AIDS after some latent period, is a dynamic process that can be modeled mathematically. Effects of available anti-viral drugs, which prevent HIV from infecting healthy cells, can also be included in the model. In this paper we illustrate control theory can be applied to a model of HIV infection. In particular, the drug dose is regarded as control input and the goal is to excite an immune response so that the symptom of infected patient should not be developed into AIDS. Finite horizon optimal control is employed to obtain the optimal schedule of drug dose since the model is highly nonlinear and we want maximum performance for enhancing the immune response. From the simulation studies, we found that gradual reduction of drug dose is important for the optimality. We also demonstrate the obtained open-loop optimal control is vulnerable to parameter variation of the model and measurement noise. To overcome this difficulty, we finally present nonlinear receding horizon control to incorporate feedback in the drug treatment.

• 제어로봇시스템학회:학술대회논문집
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• 제어로봇시스템학회 2003년도 ICCAS
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• pp.1951-1956
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• 2003

It is known that HIV (Human Immunodeficiency Virus) infection, which causes AIDS after some latent period, is a dynamic process that can be modeled mathematically. Effects of available anti-viral drugs, which prevent HIV from infecting healthy cells, can also be included in the model. In this paper we illustrate control theory can be applied to a model of HIV infection. In particular, the drug dose is regarded as control input and the goal is to excite an immune response so that the symptom of infected patient should not be developed into AIDS. Finite horizon optimal control is employed to obtain the optimal schedule of drug dose since the model is highly nonlinear and we want maximum performance for enhancing the immune response. From the simulation studies, we find that gradual reduction of drug dose is important for the optimality. We also demonstrate the obtained open-loop optimal control is vulnerable to parameter variation of the model and measurement noise. To overcome this difficulty, we finally present nonlinear receding horizon control to incorporate feedback in the drug treatment.

• Macromolecular Research
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• 제13권4호
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• pp.327-333
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• 2005

pH-sensitive hydrogels were studied as a drug carrier for the protection of insulin from the acidic environment of the stomach before releasing it in the small intestine. In this study, hydrogels based on poly(ethylene oxide) (PEO) networks grafted with methacrylic acid (MAA) or acrylic acid (AAc) were prepared via a two-step process. PEO hydrogels were prepared by ${\gamma}-ray $ irradiation (radiation dose: 50 kGy, dose rate: 7.66 kGy/h), grafted by either MAA or AAc monomers onto the PEO hydrogels and finally underwent irradiation (radiation dose: 520 kGy, dose rate: 2.15 kGy/h). These grafted hydrogels showed a pH-sensitive swelling behavior. The grafted hydrogels were used as a carrier for the drug delivery systems for the controlled release of insulin. Drug-loaded hydrogels were placed in simulated gastric fluid (SGF, pH 1.2) for 2 hr and then in simulated intestinal fluid (SIF, pH 6.8). The in vitro drug release behaviors of these hydrogels were examined by quantification analysis with a UV-Vis spectrophotometer.

• 약학회지
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• 제40권3호
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• pp.326-334
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• 1996

Effects of methanol extract of Astragali Radix (AR) on the immune responses were studied using ICR mice. Mice were divided into 4 groups (10mice/group), and methanol extracts of AR at doses of 0.05, 0.25 and 1.25g/kg were orally administered to ICR mice once a day for 2 weeks. Mice were immunized and challenged with sheep red blood cells (SRBC). The results of this study were summarized as follows; (1) Methanol extract of AR at 0.05, 0.25 and 1.25g/kg didn't affect the weight ratios of thymus to body, as compared with those in controls, but significantly increased spleen weight ratio. (2)Methanol extract of AR at 0.05 and 0.25g/kg significantly increased hemagglutination titer and splenic plaque forming cells corresponding to humoral immunity, as compared with those in controls, but their enhancements were somewhat lowered at a high dose (1.25g/kg). (3) Methanol extract of AR at 0.05 and 0.25g/kg siginificantly increased delayed-type hypersensitivity reaction resulted from cell-mediated immunity, as compared with those in controls, but not so significant increases were observed at a high dose (1.25g/kg). (4) Methanol extract of AR at 0.05 and 0.25g/kg significantly increased phagocytic activity and the number of circulating leukocyte compared with those in controls, but their enhancements were lowered at a high dose (1.25g/kg). These results suggest that methanol extract of Astragali Radix increased humoral and cell-mediated immune responses, phagocytic activity and the number of circulating leukocyte, dependent upon dose, but inhibited their enhancement effects were decreased at a high dose (1.25g/kg).

• 한방안이비인후피부과학회지
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• 제27권1호
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• pp.79-90
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• 2014

Objectives : This study was carried out to evaluate the repeated dose oral toxicity of Alismatis Rhizoma in Sprague-Dawley(SD) rats. Methods : Male and female rats were administered orally with Alismatis Rhizoma water extract of 500 mg/kg(low dosage group), 1,000 mg/kg(middle dosage group) and 2,000 mg/kg(high dosage group). We daily observed number of deaths, clinical signs and gross findings for 14 days(twice a day). After 14 days, we measured body and organs weight. Also we analyzed hematological changes. Results : No dead SD rats and no clinical signs were found during the experiment period. Also other specific changes were not found between control and treated groups in hematology and serum biochemistry. In addition no significant changes of gross body and individual organs weight. Conclusions : These results suggest that water soluble extract of Alismatis Rhizoma has not repeated dose oral toxicity and oral LD50 value was over 2,000 mg/kg in SD rats. As a result, we can determine Alismatis Rhizoma is a relatively safe substance.

• 한국임상약학회지
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• 제27권3호
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• pp.127-135
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• 2017

Background: Kawasaki disease (KD) is an acute febrile, systemic vasculitis as a leading cause of acquired heart disease in children. Intravenous immunoglobulin G (IVIG) and aspirin are the standard initial therapy in the treatment of acute KD. The purpose of this study was to investigate drug utilization in children with KD, and to compare "IVIG + high-dose aspirin" and "IVIG + moderate-dose aspirin" in preventing cardiac complications. Methods: We analyzed pediatric patient sample data compiled by the Health Insurance Review & Assessment Service from 2010 to 2015. We identified patients with KD using the KCD-6 code of M30.3. We excluded patients in chronic phase or ${\geq}1$0 years. We also excluded patients who were diagnosed KD in November or December. Drug utilization pattern were assessed in acute KD patients and 30-day and 60-day cardiac complications were investigated between "IVIG + high-dose aspirin" group and "IVIG + moderate-dose aspirin" group. Results: In acute phase, IVIG was administered to 95.8% patients, and 57.1% patients were prescribed moderate-dose aspirin and 25% patients were with high-dose aspirin. Steroid use was rapidly increased from 4.0% in 2010 to 11.3% in 2015. Both 30-day and 60-day cardiac complications occurred less in "IVIG + high-dose aspirin" group compared to "IVIG + moderate-dose aspirin" group, but not statistically significant (0.9% vs 1.8%, p=0.252 for 30-day complication rate; 1.5% vs 2.7%. p=0.073 for 60-day complication rate). Conclusion: We were not able to demonstrate which aspirin therapy is superior for preventing cardiac complications in acute KD patients and further research is warranted.

• Journal of Pharmaceutical Investigation
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• 제41권6호
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• pp.347-354
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• 2011

Repeated oral administration of loxoprofen can induce many side effects such as gastric disturbances and acidosis. Therefore, we considered alternative routes of administration for loxoprofen to avoid such adverse effects. The aim of this study was to develop an ethylene-vinyl acetate (EVA) matrix system containing a permeation enhancer for enhanced transdermal delivery of loxoprofen. The EVA matrix containing loxoprofen was fabricated and the effects of drug concentration, temperature, enhancer and plasticizer on drug release were studied from the loxoprofen-EVA matrix. The solubility of loxoprofen was highest at 40% (v/v) PEG 400. The release rate of drug from drug-EVA matrix increased with increased loading dose and temperature. The release rate was proportional to the square root of loading dose. The activation energy (Ea), which was measured from the slope of log P versus 1000/T, was 5.67 kcal/mol for a 2.0% loaded drug dose from the EVA matrix. Among the plasticizer used, diethyl phthalate showed the highest release rate of loxoprofen. Among the enhancers used, polyoxyethylene 2-oleyl ether showed the greatest enhancing effect. In conclusion, for the enhanced controlled transdermal delivery of loxoprofen, the application of the EVA matrix containing plasticizer and penetration enhancer could be useful in the development of a controlled drug delivery system.

• 한국의학물리학회:학술대회논문집
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• 한국의학물리학회 2006년도 제33회 추계학술대회 발표논문집
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• pp.12-12
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• 2006

• Environmental Analysis Health and Toxicology
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• 제22권4호
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• pp.357-366
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• 2007

To investigate the possible enhancement of genotoxicity in stress environment, we examined the of effect of genotoxic material in oxidative stress-induced condition using human tell line. Human lymphoblast cell line, TK6 was treated with hydrogen peroxide ($H_2O_2$) for induction of oxidative stress, and treated with N'-methyl-N'-nitroguanidine (MNNG), af a genetoxic material. We carried out MTS assay to set treatment doses. TK6 was treated with $H_2O_2$ at 6.75 (low dote) or $13.5\;{\mu}M$ (high dose) for 2 h, and treated with MNNG af 0.117 (low dose), 0.234 (middle dose), $0.468\;{\mu}M$ (high dose) for 2 h. As results, a treatment of MNNG induced DNA dam age as dose dependently. And TK6 treated with $H_2O_2$ at low as well as high dose followed by MNNG treatment showed higher DNA damage compared to MNNG alone treated groups. Malondialdehyde, as a marker of lipid peroxidation was increased in $H_2O_2$ and MNNG treated groups. Real-time RT-PCR analyses for expression of several antioxidative enzymes showed that catalase mRNA and glutathione peroxidase 1 mRNA expression were decreased in $H_2O_2$ and MNNG treated groups. Taken together, we conclude that genotoxicity induced by MNNG is enhanced in a condition of oxidative stress induced by $H_2O_2$ and it suggests that it should be associated with induction of lipid peroxidation and decrease of antioxidant enzymes.

• 한국의학물리학회:학술대회논문집
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• 한국의학물리학회 2004년도 제29회 추계학술대회 발표논문집
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• pp.153-156
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• 2004

식품의약품안전청은 1978년 12월 방사선 분야의 국가교정검사기관으로 지정되어 현재까지 Co-60선원을 이용 치료준위 방사선측정기에 대한 교정을 수행하고 있다. 식약청의 에어커마와 물 흡수선량 측정값은 국제도량형국(BIPM)과 측정소급성을 유지하고 있으며, 교정계수의 확장불확도는 0.9 %(k=2)이다. 식약청에서는 외부방사선에 대한 선량보증의 일환으로 1999년 전리함을 이용하여 방사선치료기관의 선량측정을 수행하였으며, 2002년부터 열형광선량계(TLD)를 이용한 선량측정체계를 확립 ${\cdot}$ 운영하고 있다. TLD 판독에 대한 측정불확도는 1.6 %(k=1)이며, 측정불확도를 감안하여 선량보증의 허용한계를 ${\pm}$ 5 %로 설정하였다. TLD 판독값을 선량으로 전환하는 과정에서 선질, 비선형성, 홀더사용 등의 영향을 보정하기 위한 보정정수를 사용하였다. 2003년도 치료방사선 선량보증사업에는 53개 기관(71개 선질)이 참여하였다. 선량보증 결과 71개 선질 중63개 선질(89 %)이 1차 측정에서 허용한계를 만족하였다. 허용한계 초과기관에 대해서는 재측정을 수행하였고, 그 결과 모두 허용한계 이내의 값을 나타냄을 확인하였다.