• Asian Pacific Journal of Cancer Prevention
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• 제13권9호
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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.

• Korean Journal of Veterinary Research
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• 제54권2호
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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.

• The Korean Journal of Pain
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• 제14권2호
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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.

• Molecular & Cellular Toxicology
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• 제5권4호
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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.

• Korean Journal of Veterinary Research
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• 제29권1호
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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.

• Journal of Pharmaceutical Investigation
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• 제24권2호
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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.

• Polymer(Korea)
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• 제25권4호
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• pp.476-485
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• 2001

In this study, we tried to design and synthesize using natural polymers (hyaluronic acid and sodium alginate) and also to make some kinds of scaffolds as sponge type for reducing the burst effect of loaded drug from them. Photo-dimerizable group was incorporated to hyaluronic acid and degradable hydrogel was prepared by the UV radiation of the polymer. The pore size and its distribution of scaffold were controlled by changing microsphere production conditions such as solution concentration and spraying pressure. It was found that drug release behavior from synthesized scaffolds was affected by hybridization of two naturally originated polymers (cinnamoylated tetrabutylammonium hyaluronate: CHT and cinnamolylated sodium alginate: CSA) and the obtained scaffolds were degraded in fairly long time (about 2 months) under in vitro environment. Therefore, we expect that obtained scaffolds can be applicable for the tissue regeneration scaffolds in the fields of orthopaedic surgery.

• YAKHAK HOEJI
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• 제39권6호
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• pp.636-644
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• 1995

Comparison of bioavailabflity (BA) of three brands of ranitidine (RT) tablets has been studied m rats. The purpose of this study was to characterize the pharniacolunetics of RT tablets in the rat and to coinpare phannacolunetic parameters of three brands of RT tablets. In addition, it was investigated whether plasma RT concentrations m humans can be predicted from pharmacokinetic parameters obtained in rats. RT was administered intravenously in dose of RT.HCI 10mg/kg and orally in dose of RT.HCI 50mg/kg as solution or crushed sample of thablets. Plasma RT concentrations were determned by HPLC. Plasma RT concentrations as a function of time were fitted to two compartment model. Plasma RT concentrations declined with a terminal half life ($t_{{1}/2{\betha}}$) of 40.9 min. The plasma RT concentration-time curve showed two peak plasma concentrations following an oral administration of solution or crushed sample in rats like humans. No significant difference among pharmacokinetic parameters was observed except $T_{max2}$ (p<0.05). The BA for crushed sample A, B and C were found to be 54.6 40.7 and 40.0%, respectively. Equivalence of $C_{max1}$ and $T_{max2}$ were guaranteed in this study. However, it was concluded that three brands of RT tablets are bioequivalent, taking the following characteristics of RT into consideration;(1) rapid onset of the effect is not required, (2) $C_{max1}$ and $T_{max2}$ do not seem to influence the effectiveness of the drug during a long-term treatment by the usual administration of twice a day. Results from this study were combined with plarmacokinetic data for RT in dogs and humans to develop a basis for interspecies scale-up of the disposition characteristics of the drug. there were similarities in the general disposition of the drug. Allometric relationships were sought between pharmacokinetic parameters nd species body weight. Significant interspecies correlations were found for total body clearance($Cl_{t}$) and steady state volume of distribution ($Bd_{ss}$). Thus, plasma RT concentrations in humans can be predicted from pharmacokinetic parameters obtained in rats.

• Journal of Information Processing Systems
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• 제13권5호
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• pp.1243-1258
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• 2017

A new medical materials scheduling system and its modeling method for the complex rescue are presented. Different from other similar system, first both the BeiDou Satellite Communication System (BSCS) and the Special Fiber-optic Communication Network (SFCN) are used to collect the rescue requirements and the location information of disaster areas. Then all these messages will be displayed in a special medical software terminal. After that the bipartite graph models are utilized to compute the optimal scheduling of medical materials. Finally, all these results will be transmitted back by the BSCS and the SFCN again to implement a fast guidance of medical rescue. The sole drug scheduling issue, the multiple drugs scheduling issue, and the backup-scheme selection issue are all utilized: the Kuhn-Munkres algorithm is used to realize the optimal matching of sole drug scheduling issue, the spectral clustering-based method is employed to calculate the optimal distribution of multiple drugs scheduling issue, and the similarity metric of neighboring matrix is utilized to realize the estimation of backup-scheme selection issue of medical materials. Many simulation analysis experiments and applications have proved the correctness of proposed technique and system.

• Applied Chemistry for Engineering
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• 제30권2호
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• pp.233-240
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• 2019

Molecular recognition technology has attracted considerable attention for improving the selectivity of a specific molecule by imprinting it on a polymer matrix. In this study, adsorption and release characteristics of chitosan based drug delivery films imprinted with sulindac (SLD) were investigated in terms of the plasticizer, temperature and pH and the results were also interpreted by the related mathematical models. The adsorption characteristics of target molecules on SLD-imprinted polymer films were better explained by the Freundlich and Sips equation than that of the Langmuir equation. The binding site energy distribution function was also useful for understanding the adsorption relationship between target molecules and polymer films. The drug release of SLD-imprinted polymer films followed the Fickian diffusion mechanism, whereas the drug release using artificial skin followed the non-Fickian diffusion behavior.