• Title/Summary/Keyword: Effect compartment model

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Effect of gender on the pharmacokinetics and metabolite formation of sulfamethazine in the rabbit (토끼의 성차가 sulfamethazine의 약동학 및 대사산물 생성에 미치는 영향)

  • Yun, Hyo-in;Park, Il-hyun
    • Korean Journal of Veterinary Research
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    • v.32 no.1
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    • pp.35-39
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    • 1992
  • SMZ is one of the most widely used antibacterial agents in veterinary medicine. It is also used as a growth promotant in many species of domestic animals There are marked species differences in its metabolism and pharmacokinetics. However, its pharmacokinetic and metabolism in rabbits. which are ragarded not only as good laboratorty animals hut also as good economical animals in its own, are lacking. Sex-differences in drug metabolism are well recognized in wide range of animal species including rats. Males are known to he more active than females. It is also know that there are Significant differences in the direction of metabolic pathways. But recently, female goats are reported to be more active in the metabolie capacity of SMZ than the other sex by Dutch researchers at Utrecht. Therefore, it is not easy to make general conclusicn of having higher SMZ metal-die capacity in the male compared to the opposite sex in every animal species. In this regard, the study on metabolic pattern of SMZ in rabbits, which are regarded as hervivorous, is of interest because the dietary habbits of rabbit are comparable to thai of goal, NEW Zealand White rabbits of each sex were given SMZ(35mg/kg) as a bolus injection into the marginalean, vein in order to study its pharmacokinetic profiles(using plasma) anc metabolic pattem(24h urine) as specified in the methods anc materials. 1. In the rabbit, the major metabolic pathway of SMZ was the acetylation(the formation of $N_4AcSMZ$). There were hydroxylation pathways(50HSMZ, $6CH_2OHSMZ$) as well, in the metabolism of SMZ in the rabbit, but minor pathways. 2. No sex differences in the metabolic direction of SMZ and its metabolites formation were found from the urinary excreted metabolites of SMZ out of 24h collected urine. 3. The concentration-time curves of SMZ(35mg/kg, iv) in the plasma compartment were fitted to a one-compartment open model when using a computer program(NONLIN). There was also no difference in the pharmacokinetic pattem of SMZ between two sexes. 4. The emergence of $N_4AcSMZ$ metabolized from SMZ was very fast in the plasma of the rabbit The elimination of $N_4AcSMZ$ was prolonged as compared to that of the parent drug Vie found no sex difference in the elimination pattern of $N_4AcSMZ$ in the rabbit.

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In vivo Growth Inhibition of Sarcoma-180 Cells by a β-Glucan from the Mushroom Ganoderma lucidum (영지(Ganoderma lucidum)의 β-Glucan에 의한 Sarcoma-180 육종암 생장 억제)

  • Han, Man-Deuk;Kim, Yong Hyun;Kim, Wan Jong
    • Journal of Life Science
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    • v.24 no.7
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    • pp.721-727
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    • 2014
  • Mushroom-derived ${\beta}$-glucan, a polysaccharide (GLP) isolated from the mycelium of Ganoderma lucidum, was previously shown to have inhibitory effects against tumor-bearing mice in vivo. We investigated the apoptotic effect of mushroom-derived ${\beta}$-glucan in a sarcoma-180 tumor cell- bearing mice model using an ELISA to determine the levels of tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) in the mice. The morphology of the tumor cells was assessed with transmission electron microscopy (TEM). GLP was injected into the tumor-bearing mice at a dose (i.p.) of 20 mg/kg for 10 days. After 30 days, the tumor mass from the inguinal region was collected, weighed, and assayed using TEM and a TNF-${\alpha}$ ELISA kit. The tumors that developed in the mice treated with GLP were 71.4% smaller than those in the control group, showing the ability of GLP to inhibit tumor growth. The levels of TNF-${\alpha}$ in the serum of the sarcoma-180 bearing mice were 12 times greater than in the serum of the nonbearing tumor mice. An ultrastructural study demonstrated that the GLP-treated sarcoma-180 tumor cells were condensed, with rearranged chromatin. In addition, the marginated chromatin in nucleus induced the nuclear compartment, and there were many vacuolization in the cell. GLP could be an effective apoptosis-inducing compound in sarcoma-type cancers.

MR Study of Wate Exchange and Cell Membrane Permeability in Rat Liver Cells Using a Tissue-Specific MR Contrast Agent (조직 특성 MR 조영제를 이용한 쥐의 간세포막의 물분자 교환 및 투과율의 MR 측정기법)

  • Yongmin Chang
    • Investigative Magnetic Resonance Imaging
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    • v.2 no.1
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    • pp.73-82
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    • 1998
  • Purpose : A precise NMR technique for measuring the rate of water exchange and cell membrane permeability across the hepatocyte membrane using liver-specific MR contrast agent is described. Materials and Methods : The rat hepatocytes isolated by perfusion of the livers were used for the NMR measurements. All experiments were performed on an IBM field cycling relaxometer operating from 0.02MHz to 60 MHz proton Larmor frequency. spin-echo pulse sequence was empolyed to measure spin-lattice relaxation time, T1. The continuous distribution analysis of water proton T1 data from rat hepatocytes containing low concentrations of the liver specific contrast agent, Gd-EOB-DTPA, modeled by a general two compartment exchange model. Results : The mean residence time of water molecule inside the hepatocyte was approximately 250 msec. The lower limit for the permeability of the hepatocyte membrane was $(1.3{\pm}0.1){\;}{\times}{\;}10^{-3}cm/sec$. The CONTIN analysis, which seeks the natural distribution of relaxation times, reveals direct evidence of the effect of diffusive exchange. the diffusive water exchange is not small in the intracellular space in the case of hepatocytes. Conclusions : Gd-EOB-DTPA, when combined with continuous distribution analysis, provides a robust method to study water exchange and membrane permeability in hepatocytes. Water exchange in hepatocyte is much slower thatn that in red blood cells. Therefore, tissue-specific contrast agent may be used as a functional agent to give physiological information such as cell membrane permeability.

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Assessment of testicular steroidogenic enzymes expression in experimental animal model following withdrawal of nandrolone decanoate

  • Min, TaeSun;Karthikeyan, Adhimoolam;Lee, Ki-Ho
    • Journal of Animal Science and Technology
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    • v.63 no.6
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    • pp.1247-1264
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    • 2021
  • Anabolic steroids are frequently used to increase the growth rate of meat-producing animals. Exposure to an anabolic-androgenic steroid, nandrolone decanoate (ND), is associated with expressional reduction of testicular steroidogenic enzymes. However, the effect of withdrawal of ND exposure on the expression of these testicular molecules has not been thoroughly explored. The current research investigated expression changes of testicular steroidogenic enzymes in rats at several recovery periods (2, 6, and 12 weeks) after the stop of ND treatment with different doses (2 and 10 mg/kg body weight) for 12 weeks. Body and testis weights were recorded, and transcript levels of molecules were determined by quantitative real-time polymerase chain reaction (PCR). The immunohistochemistry was used to examine the changes of immuno-intensities of molecules. At 6 and 12 weeks of the recovery period, the 10 mg/kg ND-treated rats were lighter than other experimental groups. The interstitial compartment vanished by ND treatment filled up as the recovery period became longer. The expression of steroidogenic acute regulatory protein was returned to the control level at 12 weeks of the recovery period. Expression levels of cytochrome P450 side-chain cleavage and 17a-hydroxylase were increased in 2 mg/kg ND-treated group at 6 weeks of the recovery period, and transcript levels of these molecules in 2 and 10 mg/kg ND-treated groups at 12 weeks of the recovery period were significantly lower than the control. Expression levels of 3β-hydroxysteroid dehydrogenase (HSD) type I and 17β-HSD type 3 in 2 mg/kg ND-treated group were comparable with those of control at 12 weeks of the recovery period, but not in 10 mg/kg ND-treated group. Expression of cytochrome P450 aromatase (Cyp19) was reverted to the control level at 2 weeks of the recovery period. Except for Cyp19, there was a visible increase of immuno-staining intensity of other testicular steroidogenic enzymes in the Leydig cells as the recovery period progressed. This research has demonstrated that the cease of ND administration could restore the expression of testicular steroidogenic enzymes close to the normal level. Nevertheless, a relatively long recovery period, compared to the ND-exposure period would be required to retrieve normal expression levels of testicular steroidogenic enzymes.

Evaluation of Myocardial Oxygen Consumption with $^{11}C$-Acetate and 3D PET/CT: By Applying Recirculation Correction Method and Modified One-Compartmental Tracer Kinetic Modeling ($^{11}C$-Acetate와 3차원 PET/CT를 이용한 심근의 산소 소모량 평가: 재순환 교정법 및 수정 단일구획 추적자 동적 모델 적용)

  • Chun, In-Kook;Hwang, Kyung-Hoon;Lee, Sang-Yoon;Kim, Jin-Su;Lee, Jae-Sung;Shin, Hee-Won;Lee, Min-Kyung;Yoon, Min-Ki;Choe, Won-Sick
    • Nuclear Medicine and Molecular Imaging
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    • v.42 no.4
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    • pp.275-284
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    • 2008
  • Purpose: We intended to evaluate myocardial oxygen consumption ($MVO_2)$ by applying recirculation correction and modified one-compartment model to have a reference range of $MVO_2$ in normal young population and to reveal the effect of recirculation on time-activity curve (TAC). Materials and Methods: In nine normal male volunteers with mean age of $26.3{\pm}4.0$, $MVO_2$ was estimated with 925 MBq (25mCi) of $^{11}C$-Acetate (Neuroscience Research Institute, Gachon University of Medicine and Science, Incheon, Korea) and PET/CT (Biograph 6, Siemens Medical Solution, Germany). Analysis software such as $MATLAB^{(R)}$ v7.1 (Mathworks, Inc., United States), $Excel^{(R)}$ 2007 (Microsoft, United States), and $SPSS^{(R)}$ v12.0 (Apache Software Foundation, United States) were used. Twenty three frames were of $12{\times}10$, $5{\times}60$, $3{\times}120$, $2{\times}300's$ duration, respectively. The modified one-compartmental model and the recirculation correction method were applied. Statistical analysis was performed by using Test of Normality, ANOVA and Post-Hoc (Scheffe's) analysis, and p-value less than 0.05 was considered as significant. Results: The normal reference ranges of $MVO_2$ were presented as $3.18-4.64\;{\times}\;10^{-4}\;ml/g/sec$, $1.91-3.94\;{\times}\;10^{-4}\;ml/g/sec$, $4.31-6.40\;{\times}\;10^{-4}\;ml/g/sec$, $2.84-4.53\;{\times}\;10^{-4}\;ml/g/sec$ and $3.42-5.00\;{\times}\;10^{-4}\;ml/g/sec$ in the septum, the inferior wall, the lateral wall, the anterior wall and the entire wall, respectively. In addition, it was noted that the dual exponentiality of the clearance curve is due to the recirculation effect and that the characteristic of the curve is essentially mono-exponential. Conclusion: $^{11}C$-Acetate is a radiotracer worthwhile to assess $MVO_2$. Re-circulated $^{11}C$ can influence TAC of $^{11}C$ in myocadia and so the recirculation correction must be considered when measuring $MVO_2$.