• Title/Summary/Keyword: Blood Compartment

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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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A Refined Method for Quantification of Myocardial Blood Flow using N-13 Ammonia and Dynamic PET (N-13 암모니아와 양전자방출단층촬영 동적영상을 이용하여 심근혈류량을 정량화하는 새로운 방법 개발에 관한 연구)

  • Kim, Joon-Young;Lee, Kyung-Han;Kim, Sang-Eun;Choe, Yearn-Seong;Ju, Hee-Kyung;Kim, Yong-Jin;Kim, Byung-Tae;Choi, Yong
    • The Korean Journal of Nuclear Medicine
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    • v.31 no.1
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    • pp.73-82
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    • 1997
  • Regional myocardial blood flow (rMBF) can be noninvasively quantified using N-13 ammonia and dynamic positron emission tomography (PET). The quantitative accuracy of the rMBF values, however, is affected by the distortion of myocardial PET images caused by finite PET image resolution and cardiac motion. Although different methods have been developed to correct the distortion typically classified as partial volume effect and spillover, the methods are too complex to employ in a routine clinical environment. We have developed a refined method incorporating a geometric model of the volume representation of a region-of-interest (ROI) into the two-compartment N-13 ammonia model. In the refined model, partial volume effect and spillover are conveniently corrected by an additional parameter in the mathematical model. To examine the accuracy of this approach, studies were performed in 9 coronary artery disease patients. Dynamic transaxial images (16 frames) were acquired with a GE $Advance^{TM}$ PET scanner simultaneous with intravenous injection of 20 mCi N-13 ammonia. rMBF was examined at rest and during pharmacologically (dipyridamole) induced coronary hyperemia. Three sectorial myocardium (septum, anterior wall and lateral wall) and blood pool time-activity curves were generated using dynamic images from manually drawn ROIs. The accuracy of rMBF values estimated by the refined method was examined by comparing to the values estimated using the conventional two-compartment model without partial volume effect correction rMBF values obtained by the refined method linearly correlated with rMBF values obtained by the conventional method (108 myocardial segments, correlation coefficient (r)=0.88). Additionally, underestimated rMBF values by the conventional method due to partial volume effect were corrected by theoretically predicted amount in the refined method (slope(m)=1.57). Spillover fraction estimated by the two methods agreed well (r=1.00, m=0.98). In conclusion, accurate rMBF values can be efficiently quantified by the refined method incorporating myocardium geometric information into the two-compartment model using N-13 ammonia and PET.

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Gastrointestinal Absorption of Phenytoin from on Oil-in-water Microemulsion

  • Kwon, Kwang-Il;Bourne, David-W.A.
    • Archives of Pharmacal Research
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    • v.20 no.5
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    • pp.480-485
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    • 1997
  • The absorption profile of phenytoin Na emulsion were examined compared to that of phenytoin suspension after oral administration in the rat. The corn oil-in-water emulsion, particle size of $184{\pm}$57.8 nm, was prepared using a microfludizer, and phenytoin Na added by shaft homogenizer. The phenytoin emulsion or suspension, 100 mg/kg, were intubated intragastrically using oral dosing needle and blood samples were withdrawn via an indwelling cannula from the conscious rat. Plasma concentrations of phenytoin were measured with HPLC using phenacetin as an internal standard. The plasma concentration versus time data were fitted to a one compartment open model and the pharmacokinetic parameters were calculated using the computer program, Boomer. The phenytoin plasma concentrations from the emulsion at each observed time were about 1.5-2 times higher than those from the suspension, significantly at time of 5, 6 and 7 hr after administration. The absorption $(k_a)$ and elimination rate constant $(k_e)$ were not altered significantly, however the AUC increased from 65.6 to $106.7{\mu}ghr/ml$ after phenytoin suspension or emulsion oral administration, respectively. From an equilibrium dialysis study, the diffusion rate constant $(k_{IE})$ was considerably higher from the phenytoin Na emulsion $(0.0439 hr{-1})$ than phenytoin suspension $(0.0014 hr{-1})$.

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A Study on Toxicity Evaluation of Combustion Gases Released from the Residental Container Fire - Efficiency Test for the Fire Gas Mask Filters (주거용 컨테이너 화재시 발생되는 연소가스의 독성 평가에 관한 연구 - 화재용 방독면 filter의 성능평가를 중심으로)

  • Lee Jung Yun;Kim Jeong Hun;Kim Youn-Hi;Jung Ki Chang
    • Journal of the Korean Society of Safety
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    • v.19 no.4 s.68
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    • pp.48-54
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    • 2004
  • The recent Ire incident in an elementary school of Chonan city causes the media focus on the fire safety of residential container buildings. In this study, real fire tests were conducted in this kind of buildings. Combustion products including $O_2,\; CO_2,\;CO,\;NOx,\;SOx,\;HCI,\;HCN$ were measured, and blood samples of lab rats were analyzed in terms of Co-Hb, Glucose, AST(GOT), ALT(GPT), in order to investigate the hazard-reduction effects of employing gas mask protected with filter during the fire emergency of residential container buildings. According to the test results, whether or not employing the filter showed a sheer difference in the toxicity of the fire-induced gases, and then the importance of wearing a gas mask was evidently demonstrated.

Meningitis Occurred during Continuous Lumbar Epidural Block -A case report- (지속적 요부 경막외 차단 중 발생한 뇌막염 -증례 보고-)

  • Lee, Seong-Yeon;Chae, Jeong-Hye;Choi, Bong-Choon;Chun, Tae-Wan;Kim, Jeong-Ho;Kim, Chan
    • The Korean Journal of Pain
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    • v.8 no.2
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    • pp.383-385
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    • 1995
  • Postpuncture headache is the most common complication of epidural block, others include abscission of the tip of catheter, epidural abscess and subarachnoid infection, etc. A 69-year-old female patient visited the Neuro-Pain Clinic of Seran General Hospital for treatment of lower back pain and both sciatica. She received continuous epidural block, psoas compartment block, lumbar facet joint block and lumbar facet thermocoagulation. During the epidural block procedure the dura was accidently punctured and auto-logous blood patch was performed. Three days later, she manifested fever, nausea, vomiting, mild neck stiffness and mental deterioration. Meningitis was suspected as the cause of these signs. The CSF study reported: protein 400 mg/dl, sugar 14 mg/dl, WBC $468/mm^3$. She was recovered from the meningitis after adequate antibiotic therapy.

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Effect of Cimetidine and Antacid on Pharmacokinetics of Minocycline (시메티딘 및 제산제가 미노싸이클린의 약물동태에 미치는 영향)

  • Jung, Eui-Cha;Park, Gee-Bae;Shin, Hwa-Woo;Choi, Young-Wook;Lee, Kwang-Pyo
    • Journal of Pharmaceutical Investigation
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    • v.21 no.4
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    • pp.247-251
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    • 1991
  • Effects of aluminum magnesium hydroxide (A) and cimetidine (C) on the pharmacokinetics of minocycline (M) were investigated in female rats. Blood samples were collected at various time intervals until 36 hrs following oral dosing of drugs. Plasma minocycline concentrations were determined by HPLC. Control group (M), $T_1$ group (M+A), $T_2$ group (A+M after 2 hrs), $T_3$ group (M+A after 2 hrs), $T_4$ group (M+C) and $T_5$ group (C+M after 2 hrs) were divided to examine interaction of the drugs with minocycline. Plasma minocyline level-time curves were well described by two-compartment open model with first-order absorption in rats. Antacid treatment was associated with reduced of 71.0, 45.9, 35.7% in minocycline absorption rate $constant(K_{\alpha})$, maximum plasma $concentration(C_{max})$, and relative $bioavailability(F_{rel})$, respectively. Cimetidine treatment group exhibited no significant changes in plasma level-time curve when compared with control group and did not affect minocycline absorption as by any of these three parameters.

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Computational Study on the Hemodynamic Behaviors of the Human Cardiovascular System with an Acute Arteriovenous Fistula (급성 동정맥루를 포함하는 인체 심혈관계의 혈류역학적 거동에 관한 수치 해석적 연구)

  • 변수영;손정락;심은보;노승탁
    • Journal of Biomedical Engineering Research
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    • v.24 no.4
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    • pp.329-337
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    • 2003
  • Blood in congenital or acquired AY fistula(arteriovenous fistula) flows from arteries directly to veins. detouring peripheral micro-circulation. This makes a great effect on the hemodynamics of human cardiovascular system. In this study, a computational method using lumped parameter mode) was proposed to simulate the cardiovascular hemodynamics of patients with acute AV fistula The cardiovascular system model with a fistula compartment in left lower limb was built using 17 standard lumped compartments. Using fourth order Runge-Kutta method. we solved numerically the unsteady linear set of the ordinary differential equations resulting from application of Kirchhoff's law to the lumped parameter hemodynamic model. The baroreceptor reflex system was implemented to explain the auto-regulation effect of the cardiovascular system with acute AV fistula.

Initial Risk Assessment of Disodium Disulphite in OECD High Production Volume Chemical Program

  • Sanghwan Song;Park, Yoonho;Park, Hye-Youn;Kwon, Min-Jeoung;Koo, Hyun-Ju;Jeon, Seong-Hwan;Na, Jin-Gyun;Park, Kwangsik
    • Toxicological Research
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    • v.18 no.1
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    • pp.23-29
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    • 2002
  • Disodium disulphite, the HPV chemical, was assigned to Korea in order to implement OECD SIDS program in 1999. It was produced about 3,200 ton/year in 1998. This report evaluates the toxic potency of disodium disulphite based on the environmental and mammalian effects as well as human exposure. Oral $LD_{50}$ in rats is 1,540 mg/kg b.w. and effects was observed to the stomach, liver and the GI track that was filled with blood. For repeated dose toxicity, the predominant effect was the induction of stomach lesion due to local irritation. The no observed adverse effect lever for local (stomach irritation) was about 217 mg/kg bw/day. There is no evidence that disodium disulphite is genotoxic in vivo. No reproductive or developmental toxicty of disodium disulphite was observed for the period up to 2 yr and over three generation. In humans, urticaria and asthma with itching, edema, rhinitis, and nasal congestion were reported. Disodium disulphite is unlikely to induce respiratory sensitization but may enhance symptom of asthma in sensitive individuals. This chemical would be mainly transported to water compartment when released to environmental compartments since it is highly water soluble (470 g/l at 20). Low K oc (2.447) indicates disodium disulphite is so mobile in soil that it may not stay in the terrestrial compartment. The chemical has been tested in a limited number of aquatic species. hem acute toxicity test to fish, 96 hr-$LC_{50}$ was > 100 mg/1. For algae, 72 hr-$XC_{50}$ was 48.1 mg/1. For daphnid, the acute toxicity value of 48 hr-$EC_{50}$ was 88.76 mg/1, and chronic value of 21day-NOEC was > 10 mg/1. Therefore, PNEC of 0.1 mg/l for the aquatic organism was obtained from the chronic value of daphnid using the assessment factor of 100. Based on these data the disodium disulphite was recommended as low priority for further post-SIDS work in OECD.

Residues of Thiamphenicol in Blood of Cultured Olive Flounder and Black Rockfish Treated by Single Oral Administration (Thiamphenicol의 단일 경구투여에 따른 넙치와 조피볼락의 혈액내 잔류 분석)

  • JUNG, Sung-Hee;SEO, Jung-Soo
    • Journal of Fisheries and Marine Sciences Education
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    • v.28 no.3
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    • pp.692-700
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    • 2016
  • This study was aimed at investigating the residual patterns of thiamphenicol (TP) in the cultured olive flounder (Paralichthys olivaceus) and black rockfish (Sebastes schlegeli) following oral administration. TP concentration were detected by high performance liquid chromatography with UV detector. The recovery rates of TP in serums ranged 77.05~97.23% (olive flounder) and 89.96~97.11% (black rockfish) for the concentration of 0.1, 1.0, $10{\mu}g/mL$, respectively. After single administration of TP (100 mg/kg body weight) by oral route in olive flounder ($700{\pm}50g$, $23{\pm}1.5^{\circ}C$) and black rockfish ($500{\pm}30g$, $23{\pm}1.5^{\circ}C$), the concentration in the serum was determined at 1, 5, 10, 15, 24, 30, 50, 168, 264 and 432 h post-dose. Two-compartment model was applied to analyze in the pharmacokinetics of TP administered to the fishes. In the serum of olive flounder, TP was detected on 10 and 15 hours after treatment were $10.08{\mu}g/mL$ and $10.06{\mu}g/mL$ as maximum level, respectively. In the serum of black rockfish, TP was detected on 15 hours after treatment were $8.88{\mu}g/mL$ as maximum level. Concentrations of TP to the fishes were not measurable at 432 hours (18 days) after treatment in all samples. Similar residual patterns of TP were revealed between the fishes. These results are helpful for estimating withdrawal time of TP which has been already in use for farmed fish treatment.

Pharmacokinetics of Anticancer Agent SB-31 in Rats & Rabbits and the Cardiovascular Effect on the Isolated Perfused Rat Heart & Blood Coagulation (SB-31의 Glycyrrhizin을 지표로 한 Rat과 Rabbit에서의 약물동태 및 심혈관계에 대한 효과 연구)

  • Kang, Won Ku;Park, Yong Soon;Lee, Dong Heum;Kwon, Kwang Il
    • Korean Journal of Clinical Pharmacy
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    • v.8 no.2
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    • pp.122-132
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    • 1998
  • SB-31 which contains Pursatilla, Licoris and Ginseng extracts was recently proved as an anticancer agent. In a preclinical effort to be applied this drug to human, pharmacokinetics of SB-31 was carried out in rats and rabbits. Glycyrrhizin(GZ), a saponin of Licoris was used as a standard ingradient for the pharmacokinetics of SB-31. The rat's blood, bile and urine samples were serially collected in femoral vein, common bile duct and bladder, respectively, after bolus i.v. injection at a dose of 1 or 1/5 ampul/rat and rabbit's blood samples from the marginal ear vein at a dose of 1 or 3 amp./rabbit. GZ and glycyrrhetic acid(GA), a major metabolite of GZ in the physiological samples were analysed by HPLC with UV detection. The decline of GZ in plasma concentration was generally biexponential at each dose. GZ was almost completely recovered in bile within 18 hour. GA wasn't detected in the samples with UV detector. In the rat, Vss and Kel at a dose of 1 and 1/5 ampul of SB-31 were $98.06\pm6.07\;ml,\;0.33\pm0.05\;hr^{-1}\;and\;65.46\pm11.19\;ml,\;0.68\pm0.25\;hr^{-1}$, respectively. Those in rabbits at a dose of 3 and 1 ampul of SB-31 were $235.24\pm30.72\;ml,\;0.13\pm0.36\;hr^{-1}\;and\;341.32\pm28.58\;ml,\;0.27\pm0.04\;hr^{-1}$, respectively. 'WinNonlin' was utilized for the compartmental analysis. A two-compartment model was chosen as the most appropriate pbarmaco-kinetic model. The data were best described by using a weighting factor of $1/y^2$. To evaluate the effect of SB-31 on cardiovascular system, serially diluted SB-31 was directly injected into coronary artery in the isolated perfused rat heart and the effect of PSF, PSH, saponins of Pursatilla, and SB-31 on PT, APTT of healthy human plasma was examined. Except the positive inotropic effect of ten times diluted solution of SB-31, there was no significant effect on LVDP, (- dp/dt)/(+dp/dt), heart rate and coronary flow in comparision with that of vehicle. SB-31 had no effect on PT but slightly delayed APTT about $6.9{\sim}11.5\%$. There was no significant effect of PSF and PSH on PT & APTT. Conclusively, SB-31 did not show any notable toxic effects on cardiovascular system.

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