• Title/Summary/Keyword: Drug Distribution

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Preparation and Characterization of Poly(lactide-co-glycolide) Micro-spheres for the Sustained Release of AZT

  • Gilson Khang;Lee, Jin-Ho;Lee, Jin-Whan;Cho, Jin-Cheol;Lee, Hai-Bang
    • Macromolecular Research
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    • v.8 no.2
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    • pp.80-88
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    • 2000
  • Biodegradable microspheres were prepared with poly(L-lactide-co-glycolide) (PLGA, 75 : 25 by mole ratio) by an oil/oil solvent evaporation method for the sustained release of anti-AIDS virus agent, AZT The microspheres of relatively narrow size distribution (7.6$\pm$ 3.8 ㎛) were obtained by controlling the fabrication conditions. The shape of microspheres prepared was smooth and spherical. The efficiency of AZT loading into the PLGA microsphere was over 93% compared to that below 15% for microspheres by a conventional water/oil/water method. The effects of Preparation conditions on the morphology and in vitro AZT release pattern were investigated. in vitro release studies showed that different release pattern and release rates could be achieved by simply modifying factors in the fabrication conditions such as the type and amount of surfactant, initial amount of loaded drug, the temperature of solvent evaporation, and so on. PLCA microspheres prepared by 5% of initial drug loading, 1.0% (w/w) of surfactant concentration, and 25$\^{C}$ of solvent evaporation temperature were free from initial burst effect and a near-zero order sustained release was observed. Possible mechanisms of the near-zero order sustained release for our system have been proposed.

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Risk Assessment and Pharmacogenetics in Molecular and Genomic Epidemiology

  • Park, Sue-K.;Choi, Ji-Yeob
    • Journal of Preventive Medicine and Public Health
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    • v.42 no.6
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    • pp.371-376
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    • 2009
  • In this article, we reviewed the literature on risk assessment (RA) models with and without molecular genomic markers and the current utility of the markers in the pharmacogenetic field. Epidemiological risk assessment is applied using statistical models and equations established from current scientific knowledge of risk and disease. Several papers have reported that traditional RA tools have significant limitations in decision-making in management strategies for individuals as predictions of diseases and disease progression are inaccurate. Recently, the model added information on the genetic susceptibility factors that are expected to be most responsible for differences in individual risk. On the continuum of health care, from diagnosis to treatment, pharmacogenetics has been developed based on the accumulated knowledge of human genomic variation involving drug distribution and metabolism and the target of action, which has the potential to facilitate personalized medicine that can avoid therapeutic failure and serious side effects. There are many challenges for the applicability of genomic information in a clinical setting. Current uses of genetic markers for managing drug therapy and issues in the development of a valid biomarker in pharmacogenetics are discussed.

Development and validation of an analytical method to quantify baphicacanthin A by LC-MS/MS and its application to pharmacokinetic studies in mice

  • Jeon, So Yeon;Kim, San;Park, Jin-Hyang;Song, Im-Sook;Han, Young Taek;Choi, Min-Koo
    • Analytical Science and Technology
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    • v.35 no.2
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    • pp.60-68
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    • 2022
  • In this study, we developed and validated a sensitive analytical method to quantify baphicacanthin A in mouse plasma using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The standard calibration curves for baphicacanthin A ranged from 0.5 to 200 ng/mL and were linear, with an r2 of 0.985. The inter- and intra-day accuracy and precision and the stability fell within the acceptance criteria. Besides, we investigated the pharmacokinetics of baphicacanthin A following its intravenous (5 mg/kg) and oral administration (30 mg/kg). Intravenously injected baphicacanthin A showed biphasic elimination kinetics with high clearance and volume of distribution values. Furthermore, baphicacanthin A showed a rapid absorption but low aqueous solubility (182.51±0.20 mg/mL), resulting in low plasma concentrations and low oral bioavailability (2.49 %). Thus, we successfully documented the pharmacokinetic properties of baphicacanthin A using this newly developed sensitive LC-MS/MS quantification method, which could be used in future lead optimization and biopharmaceutic studies.

Development of a Collection System of Bait Links to Social Media on Dark Web to Track Drug Crimes (마약 범죄 추적을 위한 다크웹 상의 소셜미디어 유인 링크 수집체계 개발)

  • Sol-Kyu Park;Jiyeon Kim;Chang-Hoon Kim
    • Proceedings of the Korean Society of Computer Information Conference
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    • 2024.01a
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    • pp.123-125
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    • 2024
  • 다크웹(Dark Web)은 마약, 불법 촬영물, 해킹, 무기 등 불법 콘텐츠의 공유 및 거래가 이루어지는 인터넷 영역으로서 최근에는 소셜미디어와 연계된 형태로 범죄 양상이 변화하고 있다. 본 논문에서는 최근 국내 외 사회 문제로 대두되고 있는 마약 범죄를 추적하기 위한 다크웹 수사 기술로서 다크웹 사용자를 소셜미디어로 유인하는 마약 정보 수집체계를 개발한다. 먼저 미국 마약단속국에서 공개한 대표적인 마약 용어 3개의 표준어 및 은어를 검색 키워드로 사용하여 마약 관련 다크웹을 수집하고, 수집된 다크웹을 크롤링하여 소셜미디어 계정 링크를 추출한다. 본 논문에서는 다양한 소셜미디어 중, 트위터 및 텔레그램 접속 링크를 수집하였으며 실험 결과, 접속 가능한 총 54개 다크웹 도메인의 9,046개 웹 페이지에서 트위터 유인 링크 567개, 텔레그램 유인 링크 118개를 추출하였다.

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Characterization and Resistance Mechanisms of A 5-fluorouracil-resistant Hepatocellular Carcinoma Cell Line

  • Gu, Wei;Fang, Fan-Fu;Li, Bai;Cheng, Bin-Bin;Ling, Chang-Quan
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.9
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    • pp.4807-4814
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    • 2012
  • Purpose: The chemoresistance of human hepatocellular carcinoma (HCC) to cytotoxic drugs, especially intrinsic or acquired multidrug resistance (MDR), still remains a major challenge in the management of HCC. In the present study, possible mechanisms involved in MDR of HCC were identified using a 5-fluorouracil (5-FU)-resistant human HCC cell line. Methods: BEL-7402/5-FU cells were established through continuous culturing parental BEL-7402 cells, imitating the pattern of chemotherapy clinically. Growth curves and chemosensitivity to cytotoxic drugs were determined by MTT assay. Doubling times, colony formation and adherence rates were calculated after cell counting. Morphological alteration, karyotype morphology, and untrastructure were assessed under optical and electron microscopes. The distribution in the cell cycle and drug efflux pump activity were measured by flow cytometry. Furthermore, expression of potential genes involved in MDR of BEL-7402/5-FU cells were detected by immunocytochemistry. Results: Compared to its parental cells, BEL-7402/5-FU cells had a prolonged doubling time, a lower mitotic index, colony efficiency and adhesive ability, and a decreased drug efflux pump activity. The resistant cells tended to grow in clusters and apparent changes of ultrastructures occurred. BEL-7402/5-FU cells presented with an increased proportion in S and G2/M phases with a concomitant decrease in G0/G1 phase. The MDR phenotype of BEL-7402/5-FU might be partly attributed to increased drug efflux pump activity via multidrug resistance protein 1 (MRP1), overexpression of thymidylate synthase (TS), resistance to apoptosis by augmentation of the Bcl-xl/Bax ratio, and intracellular adhesion medicated by E-cadherin (E-cad). P-glycoprotein (P-gp) might play a limited role in the MDR of BEL-7402/5-FU. Conclusion: Increased activity or expression of MRP1, Bcl-xl, TS, and E-cad appear to be involved in the MDR mechanism of BEL-7402/5-FU.

A survey of the use of veterinary anesthetics in Korea

  • Lee, Jae-Won;Lee, Jeong Ik;Cho, Yoon Ju;Lee, Young-Ah;Kim, Jong-In;Hwang, Bo Ram;Kim, Hyung Joon;Jhun, Hyunjhung;Han, Jin Soo
    • Korean Journal of Veterinary Research
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    • v.54 no.2
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    • pp.101-105
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    • 2014
  • This study was conducted to investigate actual conditions associated with veterinary anesthetic drug use in Korea, and to obtain responses from Korean veterinarians and researchers pertaining to the use of anesthetic drugs. To accomplish this, a nationwide survey was issued to veterinarians working at animal hospitals and to researchers in the Korean Association for Laboratory Animal Science (KALAS). A self-administered questionnaire-based survey was then conducted in which respondents were asked questions about actual conditions associated with the use of animal anesthetic drugs. The survey revealed that the distribution and management of animal medicines in Korea was quite vulnerable to misuse or abuse due to a variety of factors. Therefore, a relevant regulatory system should be strictly enforced to protect vulnerable individuals from abuse or misuse.

Appropriate Block Level in Neurolytic Lumbar Sympathetic Ganglion Block (신경파괴적 요부교감신경절 차단의 적정 부위)

  • Kim, Hee-Jung;Lee, Cheol-Oh;Shin, Yang-Sik;Lee, Youn-Woo
    • The Korean Journal of Pain
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    • v.14 no.2
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    • pp.199-206
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    • 2001
  • Background: The lumbar sympathetic ganglia are variable in both position and numbers. The aim of this study was to detect the appropriate lumbar vertebral level where the lumbar sympathetic ganglia primarily aggregate. Methods: Forty patients comprising of hyperhidrosis (26 cases), complex regional pain syndrome (10 cases), peripheral artery occlusion disease (3 cases) and postherpetic neuralgia (1 case) underwent lumbar sympathetic block. We randomly selected one of two (L2 or L3) levels and the L4 level. The position of the needle tip and distribution of dye was verified by injection of a mixture of radio-opaque dye (1.5 ml) and 4% lidocaine (1.5 ml) and subsequently confirmed by L-spine anteroposterior and a lateral view X-ray. We considered the response positive when the skin temperature increased more than $1^{\circ}C$ in 5 min. Results: In general, the positive response ratio was greater when the needle tip located at the L2 or L4 level vice L3 and when the drug was distributed on the lower half of the L4 body and in the L4/5 intervertebral disc space. In a right side block, the positive response ratio was greater when the drug was distributed on the lower half of the L4 body and in the L4/5 intervertebral disc space, although in a left side block there was no significant difference seen between the levels. The complications of the neurolytic block were alcohol neuritis (7.5%) and hypoesthesia (5%) on the L1 or L2 dermatome. Conclusions: The best effect with least chance of complication may be induced by spreading the drug on the lower half of the L4 body and/or into the L4/5 intervertebral disc space by placing the needle tip on the L4 body.

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CYP2D6 P34S Polymorphism and Mirtazapine Responses in Koreans with Major Depression

  • Jeon, Si-On;Chang, Hun-Soo;Lee, Hwa-Young;Ham, Byung-Joo;Kang, Rhee-Hun;Jeong, Yoo-Jung;Lee, Min-Soo
    • Molecular & Cellular Toxicology
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    • v.5 no.4
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    • pp.346-353
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    • 2009
  • Drug metabolism is a critical determinant of the therapeutic and adverse effects of many psychotropic drugs. The metabolism depends on the pharmacokinetics of a drug, which includes its absorption, distribution, and elimination. Psychotropic drugs are metabolized mainly by cytochrome P450 (CYP) enzymes; about 20 of these enzymes exist and they are often responsible for the rate-limiting step of drug metabolism. CYP2D6 is the best-characterized P450 enzyme that exhibits polymorphism in humans. This study determined the relationship between the CYP2D6*10 (P34S) polymorphism and the response to mirtazapine in 153 Koreans with major depressive disorder (MDD). The genotype frequencies were compared using logistic regression analysis, and between-genotype differences in the decrease in the 21-item Hamilton Depression (HAMD21) score over the 12-week treatment period were analyzed using a linear regression analysis. The proportion of remitters was lower in patients with MDD possessing the S allele than in P allele carriers after 2 weeks of mirtazapine treatment. Similarly, the reductions in the HAMD21 and Clinical Global Impression (CGI) scores in S allele carriers were smaller than those in patients with the P allele after 2 weeks of mirtazapine treatment. In the analysis of depression symptoms, the sleep and delusion scores had smaller reductions in S allele carriers. Based on the Liverpool University Neuroleptic Side Effect Rating Scale (LUNSERS), the psychic adverse effects of mirtazapine were associated with CYP2D6 P34S, while weight gain was not. These results suggest that CYP2D6 P34S affects the outcome of mirtazapine treatment in patients with MDD, and that this polymorphism may be a good genetic marker for predicting the clinical outcome of mirtazapine treatment.

Genetic properties of R plasmids in Shigella isolates of swine origin in Korea (돈(豚)에서 분리(分離)한 Shigella균유래(菌由來) R plasmid의 유전적(遺傳的) 특성(特性)에 관한 연구(硏究))

  • Choi, Won-pil;Kwun, Hae-byeng;Jung, Suk-chan
    • Korean Journal of Veterinary Research
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    • v.29 no.1
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    • pp.37-44
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    • 1989
  • This paper dealt with the distribution of Shigella spp. on 5 piggeries in Taegu and Kyungpook during the period from August to October 1987. Isolated Shigella were examined for serogrouping, antimicrobial drug resistance and detection of R plasmid. Genetic properties of R plasmid in Shigella have examined to fertility inhibition (Fi) and gel electrophoresis was performed for the isolation of plasmid DNA. The results obtained were summarised as followings; 1. Of total 2,978 samples from 5 piggeries, 82 strains (2.8%) of Shigella spp. were isolated from 82 samples. The isolated strains were identified as S dysenteriae (60 strains), S flexneri (20 strains) and S sonnei (2 strains). 2. Of the 82 strains examined 67 (95.1%) were resistant to one or more antibiotics, such as ampicillin (Am), chloramphenicol (Cm), kanamycin (Km), nalidixic acid (Na), rifampicin (Rf), streptomycin (Sm), sulfademethoxine (Su), and tetracycline (Tc) and higher resistant to Su (90.2%), Sm (63.4%) and Tc (63.4%). 3. Of the 78 resistant Shigella strains 26 (33.3%) harbored conjugative R plasmids and the transfer frequency of Sm (50.0%), Cm(33.3%) resistance was much higher than that of the other drug resistance. 4. The most common resistant patterns were SmSuTc, Su and AmSmSuTc. 5. Out of the 26 Shigella R plasm ids examined for Fi, 14(53.8%) were $Fi^+$ and the remainder were $Fi^-$. 6. The plasmid DNA profiles in Shigella spp. (9 strains) isolated from pigs were confirmed as being 2 to 9 fragments by the gel electrophoresis. Their molecular size ranged 2.17 to 87.62 kilobase (Kb). All strains of Shigella spp. consisted in 15.4 Kb plasmids.

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Palmitoylpolysaccharide-coated Liposomes As A Potential Oral Drug Carrier (경구용 약물수송체로서의 팔미토일 치환 다당체로 코팅된 리포좀)

  • Hahn, Yang-Hee;Yi, Jung-Woo;Choi, Young-Wook
    • Journal of Pharmaceutical Investigation
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    • v.24 no.2
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    • pp.73-83
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    • 1994
  • Applications of liposomes as a drug carrier for the oral delivery of poorly-absorbable macromolecular drugs have been limited, because of their instability in gastrointestinal environments including pH, bile salts, and digestive enzymes. Two polysaccharides, dextran(DX) and pullulan(PL), were introduced to the preformed liposomes in order to enhance the stability. Palmitoyl derivatives of polysaccharides, palmitoyldextran(PalDX) and palmitoylpullulan(PalPL), were synthesizd and introduced to the liposomes during preparation for the same purpose of stability. The effects of these polysaccharides coating were evaluated basically by physical properties of particle size distribution and optical microscopy, then compared with uncoated liposomes by the observations of both in vitro stability and in vovo absorption characteristics. The geometric mean diameters of polysaccharide-coated liposomes were greater than that of uncoated liposome, showing the outermost polysaccharide-coated layer under the optical microscopy. In vitro stabilities of uncoated or polysaccharides-coated liposomes were measured by turbidity changes in various pH buffer solutions containing sodium choleate as bile salts. While uncoated liposome was very sensitive to bile salts, polysaccharides-coated liposomes were stable in relatively higher concentrations of sodium choleate, giving the results of better stability of PalDX- and PalPL-coated liposomes than that of DX- and PL-coated liposomes. After liposomal encapsulation of acyclovir(ACV), an antiviral agent as a model drug, it has been administered orally to rats as dose of ACV 40 mg/kg. Plasma concentrations of ACV were assayed by HPLC and analyzed by model-independent pharmacokinetics. Pharmacokinetic parameters of Cmax, tmax, and [AUC] have been compared.

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