• Title/Summary/Keyword: two compartment model

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Synergistic effects of oxytetracycline and tiamulin against swine respiratory bacteria and their pharmacokinetics in the pigs (돼지호흡기세균에 대한 oxytetracycline과 tiamulin의 시험관내 상승작용 및 돼지에서의 약물동태학)

  • Park, Seung-chun;Yun, Hyo-in;Lee, Keun-woo
    • Korean Journal of Veterinary Research
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    • v.42 no.1
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    • pp.45-54
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    • 2002
  • The study was carried out to characterize the pharmacokinetics after intravenous (iv, 20 mg/kg) and oral (p.o. 100 mg/kg) administration as oxytetracycline (OTC) and tiamulin (TIA) mixture in swine and to determine interaction between OTC and TIA against various pig pathogenic bacteria. The antibacterial effects of OTC in combination with TIA in vitro showed synergistic effect against Salmonella typhimurium 1925, Pasteurella multocida Type A, P. multocida Type D, Krebsiella Pneumoniae 2001, K. Pneumoniae 1560, K. Pneumoniae 2208, Haemophillus pleuropneumonia S 2, and H. pleuropneumonia S 5, but against additive effect E. coli K88ab and S. choleraesuis on the basis of fractional inhibitory concentration (FIC) index. On the while, after i.v. and p.o. administration of OTC and TIA mixture, each OTC and TIA concentrations in plasma were fitted to an open two-compartment model. After i.v. administration of OTC-TIA mixture, the mean distribution half-life ($T_{1/2{\alpha}}$) of OTC and TIA in plasma showed 0.29 h and 0.17 h, and the mean elimination half-life ($T_{1/2{\beta}}$) of those was 4.36 h and 6.64 h, respectively. The mean volume of distribution at steady state ($Vd_{ss}$) of OTC and TIA was $0.85{\ell}/kg$ and $2.44{\ell}/kg$, respectively. After oral administration of OTC and TIA mixture, the mean maximal absorption concentrations ($C_{max}$) of OTC and TIA were $0.60{\mu}g/m{\ell}$ at 1.07 h ($T_{max}$) and $1.68{\mu}g/m{\ell}$ at 1.85 h ($T_{max}$), respectively. The mean elimination half-life ($T_{1/2{\beta}}$) of those showed 6.84 h and 6.36 h. In conclusion, we could suggest in this study that the combination of OTC and TIA may be recommended for the antibacterial therapy against polymicrobial infections, and both OTC and TIA showed large distribution to tissues and high $C_{max}$ after p.o. administration.

Ecological Risk Assessment of 4,4'-Methylenedianiline (4,4'-Methylenedianiline의 환경매체별 위해성평가)

  • Hyun Soo Kim;Daeyeop Lee;Kyung Sook Woo;Si-Eun Yoo;Inhye Lee;Kyunghee Ji;Jungkwan Seo;Hun-Je Jo
    • Journal of Environmental Health Sciences
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    • v.49 no.6
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    • pp.334-343
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    • 2023
  • Background: South Korea's Act on Registration and Evaluation, etc. of Chemicals (known as K-REACH) was established to protect public health and the environment from hazardous chemicals. 4,4'-Methylenedianiline (MDA), which is used as a major intermediate in industrial polymer production and as a vulcanizing agent in South Korea, is classified as a toxic substance under the K-REACH act. Although MDA poses potential ecological risks due to industrial emissions and hazards to aquatic ecosystems, no ecological risk assessment has been conducted. Objectives: The aim of this study is to assess the ecological risk of MDA by identifying the actual exposure status based on the K-REACH act. Methods: Various toxicity data were collected to establish predicted no effect concentrations (PNECs) for water, sediment, and soil. Using the SimpleBox Korea v2.0 model with domestic release statistical data and EU emission factors, predicted environmental concentrations (PECs) were derived for ten sites, each referring to an MDA-using company. Hazard quotient (HQ) was calculated by ratio of the PECs and PNECs to characterize the ecological risk posed by MDA. To validate the results of modeling-based assessment, concentration of MDA was measured using in-site freshwater samples (two to three samples per site). Results: PNECs for water, sediment, and soil were 0.000525 mg/L, 4.36 mg/kg dw, and 0.1 mg/kg dw, respectively. HQ for surface water and sediment at several company sites exceeded 1 due to modeling data showing markedly high PEC in each environmental compartment. However, in the results of validation using in-site surface water samples, MDA was not detected. Conclusions: Through an ecological risk assessment conducted in accordance with the K-REACH act, the risk level of MDA emitted into the environmental compartments in South Korea was found to be low.

Assessment of Metabolic Impairment in Alzheimer's Disease with [$^{18}F$]FDG PET: Validity and Role of Simplified Tissue Radioactivity Ratio Analysis (알쯔하이머병에서 양전자방출단층촬영을 이용한 국소뇌포도당대사의 변화에 관한 연구)

  • Kim, Sang-Eun;Na Duk-Lyul;Lee, Jeong-Rim;Choi, Yong;Lee, Kyung-Han;Choe Yearn-Seong;Kim, Doh-Kwan;Kim, Byung-Tae;Lee, Kwang-Ho;Kim, Seung-Tai P.
    • The Korean Journal of Nuclear Medicine
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    • v.30 no.3
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    • pp.299-314
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    • 1996
  • The purpose of the present study was to validate the use of tissue radioactivity ratios instead of regional metabolic rates for the assessment of regional metabolic changes in Alzheimer's disease(AD) with [$^{18}F$]FDG PET and to examine the correlation of ratio indices with the severity of cognitive impairment in AD. Thirty-seven AD Patients(age $68{\pm}9 yrs$, $mean{\pm}s.d.$; 36 probable and 1 definite AD), 28 patients with dementia of non-Alzheimer type(age $66{\pm}7 yrs$), and 17 healthy controls(age $66{\pm}4 yrs$) underwent [$^{18}F$]FDG PET imaging. Two simplified radioactivity ratio indices were calculated from 37-66 min image: region-to-cerebellar radioactivity ratio(RCR) and a composite radioactivity ratio(a ratio of radioactivity in the most typically affected regions over the least typically affected regions: CRR). Local cerebral metabolic rate for glucose(LCMRglu) was also measured using a three-compartment, five-parameter tracer kinetic model. The ratio indices were significantly lower in AD patients than in controls(RCR in temporoparietal cortex, $0.949{\pm}0.136$ vs. $1.238{\pm}0.129$, p=0.0004; RCR in frontal cortex, $1.027{\pm}0.128$ vs. $1.361{\pm}0.151$, p<0.0001; CRR, $0.886{\pm}0.096$ vs. $1.032{\pm}0.042$. p=0.0024). On the RCR analysis, 86% of AD patients showed a pattern of bilateral temporoparietal hypometabolism with or without frontal involvement; hypometabolism was unilateral in 11% of the patients. When bilateral temporoparietal hypometabolism was considered to be suggestive of AD, the sensitivity and specificity of the RCR analysis for the differential diagnosis of AD were 86% and 73%, respectively. The RCR was correlated significantly with the macroparameter K [$K_1k_3/(k_2+k_3)$] (r=0.775, p<0.0001) and LCMRglu(r=0.633, p=0.0002) measured using the kinetic model. In patients with AD, both average RCR of cortical association areas and CRR were correlated with Mini-Mental Status Examination(r=0.565, p=0.0145; r=0.642, p=0.0031, respectively), Clinical Dementia Rating(r=-0.576, p=0.0124; r=-0.591, p=0.0077), and total score of Mattis Dementia Rating Scale (r=0.574, p=0.0648; r=0.737, p=0.0096). There were also significant correlations between memory and language impairments and corresponding regional RCRs. The results suggest that the [$^{18}F$]FDG PET ratio indices, RCR and CRR, reflect global and regional metabolic rates and correlate with the severity of cognitive impairment in AD. The simplified ratio analysis may be clinically useful for the differential diagnosis and serial monitoring of the disease.

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Quantification of Myocardial Blood flow using Dynamic N-13 Ammonia PET and factor Analysis (N-13 암모니아 PET 동적영상과 인자분석을 이용한 심근 혈류량 정량화)

  • Choi, Yong;Kim, Joon-Young;Im, Ki-Chun;Kim, Jong-Ho;Woo, Sang-Keun;Lee, Kyung-Han;Kim, Sang-Eun;Choe, Yearn-Seong;Kim, Byung-Tae
    • The Korean Journal of Nuclear Medicine
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    • v.33 no.3
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    • pp.316-326
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    • 1999
  • Purpose: We evaluated the feasibility of extracting pure left ventricular blood pool and myocardial time-activity curves (TACs) and of generating factor images from human dynamic N-13 ammonia PET using factor analysis. The myocardial blood flow (MBF) estimates obtained with factor analysis were compared with those obtained with the user drawn region-of-interest (ROI) method. Materials and Methods: Stress and rest N-13 ammonia cardiac PET imaging was acquired for 23 min in 5 patients with coronary artery disease using GE Advance tomograph. Factor analysis generated physiological TACs and factor images using the normalized TACs from each dixel. Four steps were involved in this algorithm: (a) data preprocessing; (b) principal component analysis; (c) oblique rotation with positivity constraints; (d) factor image computation. Area under curves and MBF estimated using the two compartment N-13 ammonia model were used to validate the accuracy of the factor analysis generated physiological TACs. The MBF estimated by factor analysis was compared to the values estimated by using the ROI method. Results: MBF values obtained by factor analysis were linearly correlated with MBF obtained by the ROI method (slope = 0.84, r = 0.91), Left ventricular blood pool TACs obtained by the two methods agreed well (Area under curve ratio: 1.02 ($0{\sim}1min$), 0.98 ($0{\sim}2min$), 0.86 ($1{\sim}2min$)). Conclusion: The results of this study demonstrates that MBF can be measured accurately and noninvasively with dynamic N-13 ammonia PET imaging and factor analysis. This method is simple and accurate, and can measure MBF without blood sampling, ROI definition or spillover correction.

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Determination of Appropriate Sampling Frequency and Time of Multiple Blood Sampling Dual Exponential Method with $^{99m}Tc$-DTPA for Calculating GFR (사구체여과율 계산을 위한 $^{99m}Tc$-DTPA를 이용한 다중 채혈 이중지수법의 적정 채혈 횟수 및 시간의 선정)

  • Kim, Chung-Ho;O, Joo-Hyun;Chung, Yong-An;Yoo, Ie-Ryung;Sohn, Hyung-Sun;Kim, Sung-Hoon;Chung, Soo-Kyo;Lee, Hyoung-Koo
    • Nuclear Medicine and Molecular Imaging
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    • v.40 no.1
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    • pp.33-39
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    • 2006
  • Purpose: To determine appropriate sampling frequency and time of multiple blood sampling dual exponential method with $^{99m}Tc$-DTPA for calculating glomerular filtration rate (GFR). Materials & Methods: Thirty four patients were included in this study. Three mCi of $^{99m}Tc$-DTPA was intravenously injected and blood sampling at 9 different times, 5ml each, were done. Using the radioactivity of serum, measured by gamma counter, the GFR was calculated using dual exponential method and corrected with the body surface area. Using spontaneously chosen 2 data points of serum radioactivity, 15 collections of 2-sample GFR were calculated. And 10 collections of 3-sample GFR and 12 collections of 4-sample GFR were also calculated. Using the 9-sample GFR as a reference value, degree of agreement was analyzed with Kendall's $\tau$ correlation coefficients, mean difference and standard deviation. Results: Although some of the 2-sample GFR showed high correlation coefficient, over or underestimation had evolved as the renal function change. The 10-120-240 min 3-sample GFR showed a high correlation coefficient (${\tau}=0.93$), minimal difference ($Mean{\pm}SD=-1.784{\pm}3.972$), and no over or underestimation as the renal function changed. The 4-sample GFR showed no better accuracy than the 3-sample GFR. Conclusions: In the wide spectrum of renal function, the 10-120-240 min 3-sample GFC could be the best choice for estimating the patients' renal function.