• Nuclear Medicine and Molecular Imaging
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• 제41권6호
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• pp.525-529
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• 2007

Regulation for the radiopharmaceuticals should be reasonably different from that of other drugs. Radiopharmaceuticals are always used by compounding based on the doctor's order, have short half life and very low administration dose. Its pharmacological effect is not from its chemical effect but from radiation. The background for exploratory IND (Investigational New Drug) explained by the FDA was to reduce the time and resources expended on candidate products that are unlikely to suceed, new tools are needed to distinguish earlier in the process those candidates that hold promise from those that do not. In this review, basic concept for exploratory IND and RDRC guideline is summarized and various suggestions for improving and expediting procedure for new radiopharmaceutical development would be described.

• 통합자연과학논문집
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• 제4권1호
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• pp.23-30
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• 2011

Multidrug resistance (MDR) is one of the main obstacles in the chemotherapy of cancer. MDR is associated with the over expression of P-glycoprotein (P-gp), resulting in increased efflux of chemotherapy from cancer cells. Inhibiting P-gp as a method to reverse MDR in cancer patients has been studied extensively, but the results have generally been disappointing. First-generation agents were limited by unacceptable toxicity, whereas second-generation agents had better tolerability but were confounded by unpredictable pharmacokinetic interactions and interactions with other transporter proteins. Third-generation inhibitors have high potency and specificity for P-gp. Furthermore, pharmacokinetic studies to date have shown no appreciable impact on drug metabolism and no clinically significant drug interactions with common chemotherapy agents. Third-generation P-gp inhibitors have shown promise in clinical trials. The continued development of these agents may establish the true therapeutic potential of P-gp-mediated MDR reversal.

• 한국자기공명학회논문지
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• 제15권1호
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• pp.54-68
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• 2011

$^1H$ nuclear magnetic resonance (NMR) spectroscopy of biological samples has been proven to be an effective and nondestructive approach to probe drug toxicity within an organism. In this study, ketoprofen toxicity was investigated using $^1H$-NMR spectroscopy coupled with multivariate statistical analysis. Histopathologic test of ketoprofen-induced acute gastrointestinal damage in rats demonstrated a significant dose-dependent effect. Furthermore, principal component analysis (PCA) derived from $^1H$-NMR spectra of urinary samples showed clear separation between the vehicle-treated control and ketoprofen-treated groups. Moreover, PCA derived from endogenous metabolite concentrations through targeted profiling revealed a dose-dependent metabolic shift between the vehicle-treated control, low-dose ketoprofen-treated (10 mg/kg body weight), and high-dose ketoprofen-treated (50 mg/kg) groups coinciding with their gastric damage scores after ketoprofen administration. The resultant metabolic profiles demonstrated that the ketoprofen-induced gastric damage exhibited energy metabolism perturbations that increased urinary levels of citrate, cis-aconitate, succinate, and phosphocreatine. In addition, ketoprofen administration induced an enhancement of xenobiotic activity in fatty oxidation, which caused increase levels of N-isovalerylglycine, adipate, phenylacetylglycine, dimethylamine, betaine, hippurate, 3-indoxylsulfate, N,N-dimethylglycine, trimethyl-N-oxide, and glycine. These findings demonstrate that $^1H$-NMR-based urinary metabolic profiling can be used for noninvasive and rapid way to diagnose adverse drug effects and is suitable for explaining the possible biological pathways perturbed by nonsteroidal anti-inflammatory drug toxicity.

• Carbon letters
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• 제11권2호
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• pp.122-126
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• 2010

The alginate-based hydrogel was prepared as a pH-sensitive drug delivery system. To enhance the drug loading capacity, activated carbon was introduced as a drug absorbent. The iron oxide was incorporated into the alginate matrix for the magnetic transferring to the target organ. The activated carbon and iron-oxide were dispersed uniformly in the alginate hydrogel. The drug release from the alginate/activated carbon composite hydrogel was carried out in various pH conditions with vitamin B12 and Lactobacillus lamnosers as model drugs. The fast and sustainable release of drug was observed in the basic condition due to the pH-sensitive solubility of alginate. The novel drug delivery system having pH-sensitive release property and magnetic movement to target place was developed by using the alginate/activated carbon composite magnetic hydrogels.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 2006년도 Spring Conference
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• pp.109-120
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• 2006

Alzheimer's disease (AD) is an age-related neurodegenerative disorder. The pathological hallmarks of AD are senile plaques and neurofibrillary tangles in the brain. Major component of senile plaques is amyloid beta peptide(A$\beta$) which is derived from amyloid precursor protein (APP). A$\beta$ is generated through the sequential cleavage of App by $\beta$ - and $\gamma$-secretases. $\beta$-secretase excises the ectodomain of APP ($\beta$-APPs) to leave a 99-amino acid long C-terminal fragment (APP-C99-CTF) in the membrane. $\gamma$-secretase then cleaves this membrane-tethered APP-CTF within the transmembrane domain, so releasing A$\beta$ peptides and APP-intracellular domain (AICD). Thus, $\beta$- and $\gamma$-secretase are regarded to perform the key steps in the pathogenesis of AD and have become important therapeutic targets in the prevention and treatment of AD. Enormous efforts have been focused to develop the amyloid beta related drug for cure of AD becuase A$\beta$ is believed to be one of the major causes of AD. since major pharmaceutical companies in world wide base compete to develop new drug for AD, we have to be careful to choose the drug target to success the tough race. In the present talk, possible drug targets based on basic research results will be discussed. These molecules should be a good target for development of new drug for AD and be less competitive to have a good shape for world wide competition.

• 한국환경농학회지
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• 제39권3호
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• pp.246-252
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• 2020

BACKGROUND: Pesticides are broadly used to control weeds and pests, and the residues remaining in crops are managed in accordance with the MRLs (maximum residue limits). Therefore, an analytical method is required to quantify the residues, and we conducted a series of analyses to select and validate the quick and simple analytical method for tolpyralate in five agricultural products using QuEChERS (quick, easy, cheap, effective, rugged and safe) method and LC-MS/MS (liquid chromatography-tandem mass spectrometry). METHODS AND RESULTS: The agricultural samples were extracted with acetonitrile followed by addition of anhydrous magnesium sulfate, sodium chloride, disodium hydrogencitrate sesquihydrate and trisodium citrate dihydrate. After shaking and centrifugation, purification was performed with d-SPE (dispersive-solid phase extraction) sorbents. To validate the optimized method, its selectivity, linearity, LOD (limit of detection), LOQ (limit of quantitation), accuracy, repeatability, and reproducibility from the inter-laboratory analyses were considered. LOQ of the analytical method was 0.01 mg/kg at five agricultural products and the linearity of matrix-matched calibration were good at seven concentration levels, from 0.0025 to 0.25 mg/L (R²≥0.9980). Mean recoveries at three spiking levels (n=5) were in the range of 85.2~112.4% with associated relative standard deviation values less than 6.2%, and the coefficient of variation between the two laboratories was also below 13%. All optimized results were validated according to the criteria ranges requested in the Codex Alimentarius Commission (CAC) and Ministry of Food and Drug Safety (MFDS) guidelines. CONCLUSION: In conclusion, we suggest that the selected and validated method could serve as a basic data for detecting tolpyralate residue in imported and domestic agricultural products.

• 통합자연과학논문집
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• 제5권1호
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• pp.1-5
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• 2012

Quantitative structure-activity relationship (QSAR) methodologies have been applied for many years, to correlate the relationship between physicochemical properties of chemical substances and their biological activities to generate a statistical model for prediction of the activities of new chemical entities. The basic principle behind the QSAR models is that, how structural variation is responsible for the difference in biological activities of the compounds. 3D-QSAR has emerged as a natural extension to the classical Hansch and Free-Wilson approaches, which develops the 3D properties of the ligands to predict their biological activities using various chemometric techniques (PLS, G/PLS, ANN etc). It has served as a valuable predictive tool in the design of pharmaceuticals and agrochemicals. This review seeks to provide different 3D-QSAR approaches involved in drug designing process to develop structure-activity relationships and also discussed the fundamental limitations, as well as those that might be overcome with the improved methodologies.

• 약학회지
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• 제27권1호
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• pp.21-28
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• 1983

Distribution volume (Vd$_{ss}$ ) of a model basic drug, tetraethylammonium bromide (TEA) at a steady-state decreased sinificantly in glycerol and uranium-renal failure rats. Assuming carrier-mediated transport of TEA into tissues, the theoretical $Vd_{ss}$ of TEA decreases in an exponential way as the plasmal concentration of TEA increases. The relationship between $Vd_{ss}$ and plasma concentration of TEA in the experimental renal failure (ERF)-rats was similar. Therefore, the decrease in $Vd_{ss}$ of TEA in the ERF-rats seemed to be due to the saturation of the carrier system that are responsible for the tissue distribution of TEA, by the elevated plasma concentration of TEA in the ERF-rats. ERF was induced to rats with glycerol, folate, salicylate, uranium and gentamicin, respectively..

• 한국자기공명학회논문지
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• 제23권1호
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• pp.33-39
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• 2019

Studies on the interactions of proteins with partner molecules at the atomic resolution are essential for understanding the biological function of proteins in cells and for developing drug molecules. Solution NMR spectroscopy has shown remarkably useful capability for investigating properties on the weak to strong intermolecular interactions in both diluted and crowded solution such as cell lysates. Of note, the state-of-the-art in-cell NMR method has made it possible to obtain atomistic information on natures of intermolecular interactions between target proteins with partner molecules in living cells. In this mini-review, we comprehensively describe the several technological advances and developments in the in-cell NMR spectroscopy.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• 제16권4호
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• pp.233-239
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• 2013

Drug intoxication in children and adolescents is not uncommon in Korea. But the tendency of intoxication is changing with some factors, such as national surveillance system, Naderism and increasing concern among physicians. But the death rate of intoxication among adolescents is increasing in spite of decreasing total death rate of intoxication among children and adolescents. Therefore the physician must be concerned about the basic management of intoxication and figure out the common toxic substance among children and adolescents.