• Title/Summary/Keyword: S-RAT model

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Evaluation of Dermal Absorption Rate of Pesticide Chlorpyrifos Using In Vitro Rat Dermal Tissue Model and Its Health Risk Assessment

  • Kim, Su-Heyun;Jang, Jae-Bum;Park, Kyung-Hun;Paik, Min-Kyoung;Jeong, Sang-Hee
    • Biomedical Science Letters
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    • v.22 no.4
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    • pp.140-149
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    • 2016
  • All pesticides must be assessed strictly whether safe or not when agricultural operators are exposed to the pesticides in farmland. A pesticide is commonly regarded as safe when estimated dermal absorption amount is lower than the acceptable operator's exposure level (AOEL). In this study, dermal absorption rate of chlorpyrifos, a widely used organophosphate insecticide, was investigated using rat dermal tissue model. Chlorpyrifos wettable powder solved in water (250, 500 and 2,500 ppm) was applied to freshly excised rat dermal slices ($341{\sim}413{\mu}m$ thickness) on static Franz diffusion cells at $32^{\circ}C$ for 6 hours. After exposure period of 6 hours, and then washing-at residual amount of chlorpyrifos was analyzed in dermal tissues, tape strips, washing solution, washing swabs of receptor bottles and receptor fluids at 1, 2, 4, 8 and 24 hours. Chlorpyrifos was only detected in dermal tissue but not found in receptor fluid at each concentration and time point, and the absorption rate of 250, 500 and 2,500 ppm was 2.36%, 1.96% and 1.69%, respectively. The estimated exposure level of chlorpyrifos was calculated as 0.012 mg/kg bw/day. The health risk for farmers in this condition is a level of concern because the estimated exposure level is 12 times higher than AOEL 0.001 mg/kg bw/day. However, actual health risk will be alleviated than estimated because absorbed chlorpyrifos is not permeated into internal body system and only retained in skin layer.

Pharmacokinetics of a New Histone Hl Protein (p961), an Arthritis-suppressing Agent, in Rats and Rabbits (항류마치스 효과를 갖는 새로운 히스톤 H1 단백질 (p961)의 흰쥐와 토끼에 대한 약물동태)

  • 우수경;윤민혁;이재흥;권광일
    • YAKHAK HOEJI
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    • v.45 no.4
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    • pp.378-386
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    • 2001
  • A purified histone Hl protein, p961, which plays a role in mediating the condensation of DNA into chromatin, was recently proved as an arthritis-suppressing agent in the mouse CIA model. The pharmacokinetics of p961 was carried out in rats and rabbits. The rat's blood, bile and urine samples were serially collected from the femoral vein, common bile duct, and bladder respectively, after bolus i.v. injection at low (10 mg/kg) and high (30 mg/mg) doses. The rabbit's blood samples were also collected from the marginal ear vein after bolus i.v. injection at a dose 10 mg/kg. p961 and its major metabolite in the physiological samples were analyzed by reverse-phase HPLC using a Yydac C4 protein column and a multistep water-acetonitrile gradient containing 0.24% trifluoroacetic acid. The major pharmacokinetic parameters (AUC, $C_{max}$, MRT, $t_{1}$2/, $V_{ss}$ and Cl) were estimated from the time course of plasma p961 and metabolite concentrations using WinNonlin. A two-compartment model was chosen for p961 as the most appropriate pharmacokinetic model. After i.v. injection of p961 at doses of 10 mg/kg and 30 mg/kg, more than 80% of p961 was removed rapidly from the plasma within 15 min. The plasma half-life of p961 in rats and rabbits was found not to exceed 12 min. p961 (22448.9 mol wt) was rapidly cleaved to 21612 mot wt fragment and the breakdown product appeared rapidly in the circulation with no lag phase. p961 and metabolite were not detected in rat urine and bile....

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SUMRAY: R and Python Codes for Calculating Cancer Risk Due to Radiation Exposure of a Population

  • Michiya Sasaki;Kyoji Furukawa;Daiki Satoh;Kazumasa Shimada;Shin'ichi Kudo;Shunji Takagi;Shogo Takahara;Michiaki Kai
    • Journal of Radiation Protection and Research
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    • v.48 no.2
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    • pp.90-99
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    • 2023
  • Background: Quantitative risk assessments should be accompanied by uncertainty analyses of the risk models employed in the calculations. In this study, we aim to develop a computational code named SUMRAY for use in cancer risk projections from radiation exposure taking into account uncertainties. We also aim to make SUMRAY publicly available as a resource for further improvement of risk projection. Materials and Methods: SUMRAY has two versions of code written in R and Python. The risk models used in SUMRAY for all-solid-cancer mortality and incidence were those published in the Life Span Study of a cohort of the atomic bomb survivors in Hiroshima and Nagasaki. The confidence intervals associated with the evaluated risks were derived by propagating the statistical uncertainties in the risk model parameter estimates by the Monte Carlo method. Results and Discussion: SUMRAY was used to calculate the lifetime or time-integrated attributable risks of cancer under an exposure scenario (baseline rates, dose[s], age[s] at exposure, age at the end of follow-up, sex) specified by the user. The results were compared with those calculated using another well-known web-based tool, Radiation Risk Assessment Tool (RadRAT; National Institutes of Health), and showed a reasonable agreement within the estimated confidential interval. Compared with RadRAT, SUMRAY can be used for a wide range of applications, as it allows the risk projection with arbitrarily specified risk models and/or population reference data. Conclusion: The reliabilities of SUMRAY with the present risk-model parameters and their variance-covariance matrices were verified by comparing them with those of the other codes. The SUMRAY code is distributed to the public as an open-source code under the Massachusetts Institute of Technology license.

Electroacupuncture Applied to LR2 Ameliorates Pain Behavior in The Rat Model of Inflammatory Pain (행간 전침이 흰쥐 염증성 통증 모델의 통증 행동 완화에 미치는 영향)

  • Koo, Sungtae;Choi, Woo Young
    • Korean Journal of Acupuncture
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    • v.34 no.4
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    • pp.265-270
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    • 2017
  • Objectives : The present study aimed to examine the analgesic effect of electroacupuncture(EA) applied to the brook point of the Liver meridian in the rat model of inflammatory pain and to investigate involvement of endogenouse opioid in the EA-induced analgesia. Methods : Knee arthritis was induced by injection of $125{\mu}l$ of complete Freund's adjuvant into the knee joint cavity unilaterally. To examine the level of pain, weight bearing forces(WBFs) of affected limb was measured. EA treatment was given at the LR2, LI4 or non-acupoint on the contralateral limb with frequency of 2 Hz and intensity of 2 mA under gaseous anesthesia. Results : After induction of arthritis, rats subsequently showed a reduced stepping force of the affected hindlimb due to a painful knee. EA applied to the LR2 point on the contralateral hind limb produced a significant improvement of stepping force of the hind limb lasting for at least 2 h, and this effect was equivalent to that obtained by 5 mg/kg of oral indomethacin. The effect of EA was specific to the acupoint since it could not be mimicked by EA applied to the LI4 point or the arbitrary non-acupoint. The analgesic effect was blocked by pretreatment with naltrexone(10 mg/kg, i.p.). Conclusions : These results suggest that acupuncture applied to LR2, brook point of Liver meridian suppresses inflammatory pain in a rat model of knee arthritis and this effect seems to be mediated by endogenous opioid systems.

Effect of Areal Mean Rainfall Estimation Technique and Rainfall-Runoff Models on Flood Simulation in Samcheok Osipcheon(Riv.) Basin (면적 강우량 산정 기법과 강우-유출 모형이 삼척오십천 유역의 홍수 모의에 미치는 영향)

  • Lee, Hyeonji;Shin, Youngsub;Kang, Dongho;Kim, Byungsik
    • KSCE Journal of Civil and Environmental Engineering Research
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    • v.43 no.6
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    • pp.775-784
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    • 2023
  • In terms of flood management, it is necessary to analyze quantitative rainfall and runoff from a spatial and temporal perspective and to analyze runoff for heavy rainfall events that are concentrated within a short period of time. The simulation and analysis results of rainfall-runoff models vary depending on the type and input data. In particular, rainfall data is an important factor, so calculating areal mean rainfall is very important. In this study, the areal mean rainfall of the Samcheok Osipcheon(Riv.) watersheds located in the mountainous terrain was calculated using the Arithmetic Mean Method, Thiessen's Weighting Method, and the Isohyetal Method, and the rainfall-runoff results were compared by applying the distributional model S-RAT and the lumped model HEC-HMS. The results of the temporal transferability study showed that the combination of the distributional model and the Isohyetal Method had the best statistical performance with MAE of 64.62 m3/s, RMSE of 82.47 m3/s, and R2 and NSE of 0.9383 and 0.8547, respectively. It is considered that this study was properly analyzed because the peak flood volume occurrence time of the observed and simulated flows is within 1 hour. Therefore, the results of this study can be used for frequency analysis in the future, which can be used to improve the accuracy of simulating peak flood volume and peak flood occurrence time in mountainous watersheds with steep slopes.

Effect of Gamijipaesan Extracts against Mastitis Induced by Staphylococcus aureus Infection in a Rat Model through Anti-inflammatory and Antibacterial Effects (가미지패산(加味芷貝散)의 포도상구균 감염 유방염에 대한 항균활성 및 항염 효과)

  • Kwon, Ji-Myung;Kim, Dong-Chul
    • The Journal of Korean Obstetrics and Gynecology
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    • v.26 no.1
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    • pp.1-24
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    • 2013
  • Objectives: The object of this study was to observe the protective effect of Gamijipaesan aqueous extracts(GJS), which has been traditionally used in Korean medicine in obstetrics & gynecological fields as anti-infectious and anti-inflammatory agents, against mastitis induced by Staphylococcus aureus infection in a rat model through antibacterial, antiinflammatory, immunomodulatory, and anti-oxidant effects. Methods: Antibacterial activities of GJS against S. aureus were detected using standard agar microdilution methods, with the effects on the bacterial invasion and intracellular killing of individual test materials in human mammary gland carcinoma cell(MCF-7) and murine macrophages(Raw 264.7) at MIC1/2, MIC and MIC2 concentration levels. In addition, the effects on the cell viability, nitric oxide(NO), tumor necrosis factor(TNF)-${\alpha}$ and interleukin (IL)-6 productions of LPS activated Raw 264.7 cells. The changes on the mammary tissue viable bacterial numbers, myeloperoxidae(MPO), inducible nitric oxide synthetase(iNOS), TNF-${\alpha}$ and IL-6 contents were observed in the S. aureus in vivo intramammary infectious rat model. The anti-bacterial and anti-inflammatory effects were compared with ciprofloxacin and piroxicam, respectively in the present study. Results: MIC of GJS and ciprofloxacin against S. aureus were detected as $0.860{\pm}0.428$ (0.391-1.563) mg/ml and $0.371{\pm}0.262$(0.098-0.782) ${\mu}g/ml$, respectively. In addition, GJS and ciprofloxacin were also showed marked dosage-dependent inhibition of the both bacterial invasion and intracellular killing assays using MCF-7 and Raw 264.7 cells at MIC1/2, MIC and $MIC{\times}2$ concentrations, respectively. $ED_{50}$ against LPS-induced cell viabilities and NO, TNF-${\alpha}$ and IL-6 releases of GJS were detected as 0.72, 0.04, 0.08 and 0.11 mg/ml, and as 19.04, 4.18, 5.37 and 4.27 ${\mu}g/ml$ in piroxicam, respectively. 250 and 500 mg/kg of GJS also inhibit the intramammary bacterial growth, MPO, iNOS, TNF-${\alpha}$ and IL-6 contents in S. aureus in vivo intramammary infected rats, respectively. GJS 500 mg/kg showed quite similar antibacterial and anti-infectious effects as compared with ciprofloxacin 40 mg/kg and also showed similar anti-inflammatory effects as piroxicam 10 mg/kg, in S. aureus in vivo intramammary infectious models. Conclusions: The results obtained in this study suggest that over 250 mg/kg of GJS showed favorable anti-infectious effects against S. aureus infection in a rat model through their antibacterial, anti-inflammatory, immunomodulatory and anti-oxidant effects and therefore expected that GJS can be used as alternative therapies, having both anti-inflammatory and anti-infectious activities. However, more detail mechanism studies should be conducted in future with the efficacy tests of individual herbal composition of GJS and the screening of the biological active compounds in individual herbs. In the present study, GJS 500 mg/kg showed quite similar anti-infectious effects were detected as compared with ciprofloxacin 40 mg/kg treated rats, and also GJS shows quite similar anti-inflammatory effects as compared with piroxicam 10 mg/kg in S. aureus in vivo intramammary infectious rats, but ciprofloxacin did not showed any anti-inflammatory effects, and piroxicam did not showed anti-infectious effects in this study.

The Effect of Woohwangcheongsim-won for Delayed Neuronal Death in OGD(Oxygen-Glucose Deprivation) Model (배양 대뇌신경세포의 저당-저산소증 모델에서 우황청심원에 의한 세포사 방지 연구)

  • 원철환;정승현;신길조;문일수;이원철
    • The Journal of Korean Medicine
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    • v.23 no.4
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    • pp.125-139
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    • 2002
  • Objectives: The purpose of this investigation is to evaluate the effects of Woohwangcheongsim-won and to study the mechanism for neuronal death protection in OGD (oxygen-glucose deprivation) model with embryonic day 20 (E20) cortical cells of a rat (Sprague Dawley). Methods: E20 cortical cells were dissociated in neurobasal media and grown for 14 days in vitro (DIV). On 14 DIV, Woohwangcheongsim-won was added to the culture media for 72 hrs. On 17 DIV, cells were given an oxygen-glucose deprivation shock (2hrs and 4hrs) and further incubated in normoxia for another three days. On 20 DIV, Woohwangcheongsim-won's effects for neuronal death protection were evaluated by LDH assay and the mechanisms were studied by Bcl-2, Bak, Bax, caspase family. Results & Conclusions: 1. This study indicates that Woohwangcheongsim-won's effects for neuronal death protection in OGD model is confirmed by LDH assay in culture method of embryonic day 20(E20) cortical neuroblasts. 2. Woohwangcheongsim-won's mechanisms for neuronal death protection in OGD model are to restrain inflow of cytochrome c into cellularity caused by Bcl-2 increase (2hrs and 4hrs), to reduce the caspase cascade initiator caspase-8 (4hrs).

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Genome Wide Expression Analysis of the Effect of Woowhangchongshim-won on Rat Brain Injury

  • Kim, Bu-Yeo;Lim, Se-Hyun;Kim, Hyun-Young;Kim, Young-Kyun;Lim, Chi-Yeon;Cho, Su-In
    • The Journal of Internal Korean Medicine
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    • v.30 no.3
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    • pp.594-603
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    • 2009
  • Objectives : ICH breaks down blood vessels within the brain parenchyma, which finally leads to neuronal loss, drugs to treat ICH have not yet been established. In this experiment, we measured the effect of Woowhangchongshim-won (WWCSW) on intracerebral hemorrhage (ICH) in rat using microarray technology. Methods : We measured the effect of WWCSW on ICH in rat using microarray technology. ICH was induced by injection of collagenase type IV, and total RNA was isolated. Image files of microarray were measured using a ScanArray scanner, and the criteria of the threshold for up- and down-regulation was 2 fold. Hierarchical clustering was implemented using CLUSTER and TREEVIEW program, and for Ontology analysis. GOSTAT program was applied in which p-value was calculated by Chi square or Fisher's exact test based on the total array element. Results : WWCSW-treatment restored the gene expression altered by ICH-induction in brain to the levels of 76.0% and 70.1% for up- and down-regulated genes, respectively. Conclusion : Co-regulated genes by ICH model of rat could be used as molecular targets for therapeutic effects of drug including WWCSW. That is, the presence of co-regulated genes may represent the importance of these genes in ICH in the brain and the change of expression level of these co-regulated genes would also indicate the functional change of brain tissue.

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Red Seaweed (Hypnea Bryodies and Melanothamnus Somalensis) Extracts Counteracting Azoxymethane-Induced Hepatotoxicity in Rats

  • Waly, Mostafa Ibrahim;Al Alawi, Ahmed Ali;Al Marhoobi, Insaaf Mohammad;Rahman, Mohammad Shafiur
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.12
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    • pp.5071-5074
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    • 2016
  • Background: Azoxymethane (AOM) is a well-known colon cancer-inducing agent in experimental animals via mechanisms that include oxidative stress in rat colon and liver tissue. Few studies have investigated AOM-induced oxidative stress in rat liver tissue. Red seaweeds of the genera Hypnea Bryodies and Melanothamnus Somalensis are rich in polyphenolic compounds that may suppress cancer through antioxidant properties, yet limited research has been carried out to investigate their anti-carcinogenic and antioxidant influence against AOM-induced oxidative stress in rat liver. Objective: This study aims to determine protective effects of red seaweed (Hypnea Bryodies and Melanothamnus Somalensis) extracts against AOM-induced hepatotoxicity and oxidative stress. Materials and Methods: Sprague-Dawley rats received intraperitoneal injections of AOM, 15 mg/kg body weight, once a week for two consecutive weeks and then orally administered red seaweed (100 mg/kg body-weight) extracts for sixteen weeks. At the end of the experiment all animals were overnight fasted then sacrificed and blood and liver tissues were collected. Results: AOM treatment significantly decreased serum liver markers and induced hepatic oxidative stress as evidenced by increased liver tissue homogenate levels of nitric oxide and malondialdehyde, decreased total antioxidant capacity and glutathione, and inhibition of antioxidant enzymes (catalase, glutathione peroxidase, glutathione S-transferase, glutathione reductase and superoxide dismutase). Both red seaweed extracts abolished the AOM-associated oxidative stress and protected against liver injury as evidenced by increased serum levels of liver function markers. In addition, histological findings confirmed protective effects of the two red seaweed extracts against AOM-induced liver injury. Conclusion: Our findings indicate that red seaweed (Hypnea Bryodies and Melanothamnus Somalensis) extracts counteracted oxidative stress-induced hepatotoxicity in a rat model of colon cancer.

Regulation of Choline Transport by Oxidative Stress at the Blood-Brain Barrier In Vitro Model

  • Kang, Young-Sook;Lee, Hyun-Ae;Lee, Na-Young
    • Biomolecules & Therapeutics
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    • v.16 no.1
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    • pp.14-20
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    • 2008
  • In the present study, we examined how the transport of choline is regulated at the blood-brain barrier (BBB) under the central nervous system (CNS) cellular damages by oxidative stress using a conditionally immortalized rat brain capillary endothelial cells (TR-BBB), in vitro the BBB model. It was also tested whether the choline uptake is influenced by membrane potential, extracellular pH, protonophore (FCCP) and amiloride in TR-BBB cells. In result, $[^3H]choline$ uptake was inhibited by FCCP and dependent on extracellular pH. The treatment of TR-BBB cells with 20 ng/mL tumor necrosis $factor-{\alpha}$ $(TNF-{\alpha})$, 10 ng/mL lipopolysaccharide (LPS), 100 ${\mu}M$ diethyl maleate (DEM) and 100 ${\mu}M$ glutamate resulted in 3.0-fold, 2.6-fold, 1.8-fold and 2.0-fold increases of $[^3H]choline$ uptake at the respective peak time, respectively. In contrast, hydrogen peroxide and raffinose did not show any significant effects on choline uptake. In addition, choline efflux was significantly inhibited by $TNF-{\alpha}$, LPS and DEM producing cell damage states. In conclusion, the influx and efflux transport system for choline existed in TR-BBB cell line and this process was affected by several oxidative stress inducing agents.