• Title/Summary/Keyword: Assay error

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The Influence of Assay Error on Amikacin Pharmacokinetics the Nonlinear Least Square Regression and Bayesian Analysis in Gastric Cancer Patients (위암환자에서 비선형최소자승 회귀분석과 베이시안 분석에 의한 아미카신의 약물동태에 분척오차의 영향)

  • Choi, Jun-Shik;Burm, Jin-Pil
    • Korean Journal of Clinical Pharmacy
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    • v.18 no.1
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    • pp.11-17
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    • 2008
  • 아미카신은 그람음성균 감염에 사용하는 아미노글리코사이드계 항생제로 이독성 및 신독성 등의 부작용과 큰 개인차로 혈중농도 모니터를 통한 투여계획이 필요한 약물이다. 본 연구에서는 16명의 위암환자에서 비선형최소자승 회귀분석과 베이시안 분석에 의한 아미카신의 약물동태에 분석오차의 영향을 연구하였다. 약물투여는 아미카신 7.5 mg/kg을 30분에 걸쳐 12시간 간격으로 등속 주입하였으며, 혈액 채취는 정상상태에 도달되었다고 판단되는 첫 약물투여 72시간 후에, 약물 주입 5분전과 주입이 끝난 뒤 30분과 2시간에서 세차례 채취하였다. 혈청중 약물농도는 형광편광면역법으로 측정하였다. 분석오차를 위해 0, 5, 15, 30, 60 및 $80\;{\mu}g/ml$에 해당하는 아미카신 혈중농도(C)을 네차례 측정하여 각 혈중농도의 표준편차 (SD)을 구하였다 아미카신 분석오차를 위한 다항식이 $SD=0.3017+(0.00538C)+(0.00112C^2)$, $R^2=0.974$이었다 이 식에서 구한 SD 값으로 분석시 가중치를 주었을 때, 비선형최소자승 회귀분석에 의한 아미카신의 약물동태학적 파라메타($V_d$, $K_{el}$, $K_{slpoe}$, $t_{1/2}$)에 유의성있는 영향을 주었으나, 베이시안 분석에 의한 아미카신의 약물동태학적 파라메타에는 영향이 없었다. 이 다항식에 의한 분석오차를 비선형최소자승 회귀분석에 의한 아미카신 약물동태학적 파라메타 분석시 적절히 사용하면 안전하고 효율적인 투여계획을 할 수 있다.

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The Influence of Assay Error on Tobramycin Pharmacokinetics using the Nonlinear Least Square Regression and Bayesian Analysis in Gastric Cancer Patients (위암환자에서 비선형 최소자승 회귀분석과 베이시안 분석에 의한 토브라마이신의 약물동태에 분석오차의 영향)

  • Choi, Jun-Shik;Burm, Jin-Pil
    • Korean Journal of Clinical Pharmacy
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    • v.19 no.1
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    • pp.43-49
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    • 2009
  • 토브라마이신은 그람음성균 감염에 사용하는 아미노글리코사이드계 항생제로 이독성 및 신독성 등의 부작용과 큰 개인차로 혈중농도 모니터를 통한 투여계획이 필요한 약물이다. 본 연구에서는 16명의 위암환자에서 비선형 최소자승 회귀분석과 베이시안 분석에 의한 토브라마이신의 약물동태에 분석오차의 영향에 대하여 연구하였다. 약물투여는 토브라마이신 1-2 mg/kg을 30분에 걸쳐 8시간 간격으로 등속 주입하였으며, 혈액 채취는 정상상태에 도달되었다고 판단되는 첫 약물투여 72시간 후에, 약물 주입 5분전과 주입이 끝난 뒤 30분과 2시간에서 세차례 채취하였다. 혈청중 약물농도는 형광편광면역법으로 측정 하였다. 분석오차를 위해 0, 1, 2, 4, 8 및 12 ${\mu}g/mL$에 해당하는 토브라마이신 혈중농도(C)을 네차례 측정하여 각 혈중농도의 표준편차 (SD)을 구하였다. 토브라마이신 분석오차를 구하기 위한 다항식이 SD = 0.0224+0.0540C+0.00173C2, $R^2$ = 0.935이었다. 이 식에서 구한 SD 값으로 분석시 가중치를 주었을 때, 비선형 최소자승 회귀분석에 의한 토브라마이신의 약물동태학적 파라메타 ($V_d$, $K_{el}$, $K_{slpoe}$, $t_{1/2}$)에 유의성있는 영향을 주었으나, 베이시안 분석에 의한 토브라마이신의 약물동태학적 파라메타에는 영향이 없었다. 이 다항식으로 부터 구한 분석오차를 토브라마이신의 비선형 최소자승 회귀분석을 이용한 약물동태 연구 및 파라메타 분석에 적용하여 좀 더 정확한 투여용량을 결정할 수 있으며, 더 나아가 토브라마이신 약물동태 시뮬레이션 연구에 응용할 수 있다.

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Fecal Calprotectin Assay at an Early Stage of Treatment Can Be Used as a Surrogate Marker to Predict Clinical Remission and Mucosal Healing in Pediatric Crohn's Disease

  • Lee, Yeoun Joo;Park, Jae Hong
    • Pediatric Gastroenterology, Hepatology & Nutrition
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    • v.25 no.5
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    • pp.396-405
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    • 2022
  • Purpose: This study evaluated the predictive role of fecal calprotectin (FC) measured at an early stage of treatment for monitoring clinical remission (CR) after six months and endoscopic remission (ER) after one year of treatment in pediatric Crohn's disease (CD). Methods: This retrospective study included 45 patients who simultaneously underwent ileocolonoscopy and FC testing during follow-up. FC levels were measured before and after six weeks of treatment. CR was assessed after six months of treatment using Pediatric Crohn' s Disease Activity Index and acute-phase reactants. ER was assessed after one year using the Simple Endoscopic Score for Crohn's Disease. Results: Twenty-nine (64.4%) patients used oral prednisolone for remission induction and 16 (35.6%) patients used anti-tumor necrosis factor-alpha. Thirty (66.7%) patients achieved CR, while 24 (53.3%) achieved ER. The FC level measured after six weeks of treatment could predict CR (χ2=9.15, p=0.0025) and ER (χ2=12.31, p=0.0004). The δFC could predict CR (χ2=7.91, p=0.0049), but not ER (χ2=1.85, p=0.1738). With a threshold of ≤950.4 ㎍/g, FC at week six could predict CR with 76.7% sensitivity and 73.3% specificity. The area under the curve (AUC) was 0.769 (standard error 0.0773, p=0.0005). The same threshold predicted ER with 87.5% sensitivity and 71.4% specificity. The AUC was 0.774 (standard error 0.074, p=0.0002). Conclusion: FC assay at an early stage of treatment can be used as a surrogate marker to predict CR and mucosal healing in pediatric CD.

Potential Errors in Committed Effective Dose Due to the Assumption of a Single Intake Path in Interpretation of Bioassay Results (바이오어세이 결과 해석에서 단일 섭취경로 가정에 따르는 예탁유효선량의 잠재오차)

  • Lee, Jong-Il;Lee, Jai-Ki
    • Journal of Radiation Protection and Research
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    • v.31 no.3
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    • pp.135-140
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    • 2006
  • Intakes of radionuclides through both inhalation and ingestion pathways may occur particularly in an incident involving unsealed radionuclides. If one assume only one intake path in this case, which is usual in routine monitoring, a significant error in the evaluated committed effective dose($E_{50}$) may result. In order to demonstrate the potential errors, variations of the resulting committed effective doses were analyzed for different fractions of the inhaled activities to the total intake of $^{241}Am$. Simulated bioassav measurements for the lungs, urine and feces were generated based on the biokinetic model and data of the radionuclide, 5 ${\mu}m$ AMAD and absorption type M for inhalation, for various inhalation fractions. The potential errors in $E_{50}$ due to the assumption of one intake path were in the range from -100% to as large as +34,000% when the bioassays were made 3 days after the intakes. Larger errors are expected when only the feces assay is applied while inhalation intake exists. A strategy which employs two types of bioassay was proposed to reduce the error caused by a misjudgement of the intake path.

Bioactivity Analysis of Curcuminoids from Turmeric using On-line Screening HPLC-ABTS (On-line Screening HPLC-ABTS를 이용한 강황으로부터 Curcuminoids의 생물활성 분석)

  • Choi, Sun Do
    • Journal of Applied Biological Chemistry
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    • v.56 no.3
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    • pp.137-139
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    • 2013
  • Free radical scavengers in the bisdemethoxycurcumin (BDMC), demethoxycurcumin (DMC) and curcumin of turmeric (Curcuma longa) were screened, identified, quantified and isolation using coupled off-line-2,2'-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid) (ABTS) and on-line screening high-performance liquid chromatography (HPLC)-ABTS assay. There was a very small margin of error between the off-line-ABTS method and the on-line screening HPLC-ABTS method.

Detection of Escherichia coli Using Flow Cytometry (유세포 분석기를 이용한 대장균 검출에 관한 연구)

  • Kim, Ji-Hye;Park, Sang-Won;Cho, Young Sik
    • Journal of Environmental Science International
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    • v.26 no.1
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    • pp.11-21
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    • 2017
  • In this study, bacterial growth was assessed by flow cytometry analysis of fluorescent probes-stained bacteria. Flow cytometry has many advantages of rapid analytical time, a low standard deviation, and highly sensitive detection of live and Dead E.coli over colony forming assay. When untreated bacteria were stained by using Thiazole Orange (TO) and Propidium Iodide (PI), double staining had a short analytical time as compared with that of single staining while its error rate was similar to that of single staining. Through double staining experiments, it was determined that optimal concentrations for TO and PI staining were 420 nM and $9.6{\mu}M$, respectively.

High Throughput Screening and Directed Evolution of Tyrosine Phenol-Lyase (Tyrosine Phenol-Lyase의 고속탐색기술 개발 및 방향성 분자진화)

  • Choi Su-Lim;Rha Eu-Gene;Kim Do-Young;Song Jae-Jun;Hong Seung-Pyo;Sung Moon-Hee;Lee Seung-Goo
    • Microbiology and Biotechnology Letters
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    • v.34 no.1
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    • pp.58-62
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    • 2006
  • Rapid assay of enzyme is a primary requirement for successful application of directed evolution technology. Halo generation on a turbid plate would be a method of choice for high throughput screening of enzymes in this context. Here we report a new approach to prepare turbid plates, by controlling the crystallization of tyrosine to form needle-like particles. In the presence of tyrosine phenol-lyase (TPL), the needle-like tyrosine crystals were converted to soluble phenol rapidly than the usual rectangular tyrosine crystals. When an error-prone PCR library of Citrobacter freundii TPL was spread on the turbid plate, approximately 10% of the colonies displayed recognizable halos after 24 hours of incubation at $37^{\circ}C$. Representative positives from the turbid plates were transferred to LB-medium in 96-wellplates, cultivated overnight, and assayed for the enzyme activity with L-tyrosine as the substrate. The assay results were approximated to be proportional to the halo size on turbid plates, suggesting the screening system is directly applicable to the directed evolution of TPL. Actually, two best mutants on the turbid plates were identified to be $2{\sim}2.5$ and 1.5-fold improved in the activity.

Diagnosis of inherited metabolic disorders based on their diverse clinical features and laboratory tests (유전성 대사질환의 임상증상과 진단)

  • Yoo, Han-Wook
    • Clinical and Experimental Pediatrics
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    • v.49 no.11
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    • pp.1140-1151
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    • 2006
  • Inherited metabolic disorders are individually rare but as a whole, they are nor rare. Since Archibald Garrod introduced a concept of "inborn error of metabolism" or "chemical individuality", more than 500 diseases are currently known, affecting approximately one in 500 newborns cumulatively. They frequently manifest with acute, life-threatening crisis that require immediate specific intervention or they present with insidious diverse symptoms and signs involving multiple visceral organs or tissues as well as central nervous system, hampering a correct diagnosis. In addition, many pediatricians are not familiar with all diagnostic and therapeutic strategies for diverse inherited metabolic disorders. However, the prognosis of affected children are heavily dependent on rapid and effective treatment. In this lecture, practical guidelines for the specific diagnosis based on diverse clinical features of inherited metabolic disorders will be described. Many sophisticated laboratory tests are available for confirmatory diagnosis of each disease, which challenge to general pediatricians with respect to knowledge about biochemical metabolite assay test, enzymatic test and DNA diagnostic tests. Sample collections, indications, methods and interpretation of results in varying laboratory tests will be listed as well.

Diagnosis of Inherited Metabolic Disorders Based on Their Diverse Clinical Features and laboratory Tests (유전성 대사질환의 임상증상과 진단)

  • Yoo, Han-Wook
    • Journal of The Korean Society of Inherited Metabolic disease
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    • v.13 no.1
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    • pp.1-19
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    • 2013
  • Inherited metabolic disorders are individually rare but as a whole, they are nor rare. Since Archibald Garrod introduced a concept of "inborn error of metabolism" or "chemical individuality", more than 600 diseases are currently known, affecting approximately one in 500 newborns cumulatively. They frequently manifest with acute, life-threatening crisis that requires immediate specific intervention or they present with insidious diverse symptoms and signs involving multiple visceral organs or tissues as well as central nervous system, hampering a correct diagnosis. In addition, many pediatricians are not familiar with all diagnostic and therapeutic strategies for diverse inherited metabolic disorders. However, the prognosis of affected children are heavily dependent on rapid and effective treatment. In this lecture, practical guidelines for the specific diagnosis based on diverse clinical features of inherited metabolic disorders will be described. Many sophisticated laboratory tests are available for the confirmatory diagnosis of each disease, which is challenging to general pediatricians with respect to knowledge about biochemical metabolite assay test, enzymatic test and DNA diagnostic tests. Sample collections, indications, methods and interpretation of results in varying laboratory tests will be listed as well.

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Status of High Risk Group Fabry Disease Screening in Korea by Measuring Globotriacocylceramide in Body Fluid using Electrospray-MS/MS (탠덤매스에의한 체액 중 Globotriaocylceramide(Gb-3)의 측정을 이용한 한국인 고 위험도군에서의 파브리병 스크리닝)

  • Yoon, Hye-Ran
    • YAKHAK HOEJI
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    • v.55 no.1
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    • pp.56-63
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    • 2011
  • Fabry disease (FD) is an X-linked inborn error of glycoshpingolipid metabolism resulting from mutation in the enzyme ${\alpha}$-galactosidase A gene. The disease is an X-linked lipid storage disorder and the lack of ${\alpha}$-Gal A causes an intracellular accumulation of glycosphingolipids, mainly globotriaosylceramide (Gb-3). Measurement of Gb-3 in plasma has clinical importance for monitoring after enzyme replacement therapy for confirmed FD patients. Using electrospray ionization MS/MS we had developed, a simple, rapid, and highly sensitive analytical method for Gb-3 in plasma was used for the purpose of screening FD among high risk groups in Korean population. To date, no comprehensive results for FD screening have been performed and reported in Korea. We screened 1,100 outpatients from 13 hospitals (including clinics) to assess the incidence of FD among patients in high risk groups. For patients with borderline level amount of Gb-3, we repeated Gb-3 or performing complementary or confirmative assay with ${\alpha}$-Gal A activity and DNA mutaion analysis for confirmation diagnosis. Of 1,100 we diagnosed 3 FD with 2 classical type and 1 carrier (0.27%).