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Enantioselective Determination of Cetirizine in Human Urine by HPLC

  • Choi, Sun-Ok;Lee, Seok-Ho;Kong, Hak-Soo;Kim, Eun-Jung;Parkchoo, Hae-Young
    • Archives of Pharmacal Research
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    • 제23권2호
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    • pp.178-181
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    • 2000
  • In order to study the simultaneous determination of (+)- and (-)-cetirizine in human urine we have developed a chiral separation method by HPLC. A chiral stationary phase of $\alpha$$_1$-acidglycoprotein, the AGP-CSP was used to separate the enantiomers. The pH of the phosphate buffer, as well as the content of the organic modifier in the mobile phase, markedly affected the chromatographic separation of (+)- and (-)-cetirizine. A mobile phase of 10 m㏖/1 phosphate buffer (pH 7.0)-acetonitrile (95 : 5, v/v) was used for the urine assays. Ultraviolet absorption was monitored at 230nm and roxatidine was employed as the internal standard for quantification. (+)-Cetirizine, (-)-cetirizine and the internal standard were eluted at retention times of 12, 16, and 32 mins, respectively. The detection limit for cetirizine enantiomers was 400 ng/$m\ell$ of urine. A pharmacokinetic study was conducted with the help of 5 healthy female volunteers who were administered with a single oral dose of racemic cetirizine (20 mg). The peak area ratios provided by the cetirizine enantiomers were linear(r>0.997) over a concentration range of 2.5-200 ${\mu}g/ml$. The peak of the excreted cetirizine enantiomers appeared in the urine sample during the period of 1-2 hrs following the administration of the oral dose. The excreted level of (+)-cetirizine was slightly higher than (-)-cetirizine but the difference was not statistically significant. However, this method appears to have applications for enantioselective pharmacokinetic studies of racemic drugs.

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Suppressive Effects of Furonaphthoquinone NFD-37 on the Production of Lipopolysaccharide-Inducible Inflammatory Mediators in Macrophages RAW 264.7

  • Kim Min-Hee;Shin Hyun-Mo;Lee Yong Rok;Chung Eun Yong;Chang Yoon Sook;Min Kyung Rak;Kim Youngsoo
    • Archives of Pharmacal Research
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    • 제28권10호
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    • pp.1170-1176
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    • 2005
  • 2-Methyl-2-(2-methylpropenyl)-2,3-dihydronaphthoquinone[2,3-b]furan-4,9-dione (N FD-37) is a synthetic furonaphthoquinone compound. In this study, we determined that NFD-37 could inhibit the lipopolysaccharide (LPS)-induced production of inflammatory mediators in macrophages RAW 264.7. This compound inhibited LPS-induced nitric oxide (NO) or prostaglandin (PG) $E_{2}$ production in dose-dependent manners, with $IC_{50}$ values of 7.2 ${\mu}M$ and 5.3 ${\mu}m$, respectively. As the positive controls, pyrrolidine dithiocarbamate (30 ${\mu}M$) exhibited a $57{\%}$ inhibition of NO production, and NS-398 ($1{\mu}M$) manifested a $48{\%}$ inhibition of $PGE_2$ production. The inhibitory effects of NFD-37 on NO and $PGE_2$ production were determined to occur in conjunction with the suppression of inducible NO synthase or cyclooxygenase-2 expression. NFD-37 also inhibited the production of LPS-inducible tumor necrosis factor-${\alpha}$, interleukin (IL)-$1{\beta}$ and IL-6, at $IC_{50}$ values of 4.8-8.9 ${\mu}M$. We also determined the anti-inflammatory efficacy of NFD-37 using carrageenin-induced paw edema in experimental mice.

Scoparone from Artemisia capillaris Inhibits the Release of Inflammatory Mediators in RAW 264.7 Cells upon Stimulation Cells by Interferon-${\gamma}$ Plus LPS

  • Jang Seon Il;Kim Young-Jun;Lee Woo-Yiel;Kwak Kyung Chell;Baek Seung Hwa;Kwak Gyu Beum;Yun Young-Gab;Kwon Tae-Oh;Chung Hun Taeg;Chai Kyu-Yun
    • Archives of Pharmacal Research
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    • 제28권2호
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    • pp.203-208
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    • 2005
  • Scoparone is a major component of the shoot of Artemisia capillaris (Compositae), which has been used for the treatment of hepatitis and biliary tract infection in oriental countries. In the present study we observed that, scorparone exhibited no cytotoxic effect in unstimulated macrophages, but reduced the release of nitric oxide (NO) and prostaglandin $E_2\;(PGE_2)$ upon stimulation by IFN-${\gamma}$/LPS or LPS. The inhibitory effects were found to be in conjuction with the suppression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in IFN-${\gamma}$/LPS stimulated RAW 264.7 cells. Moreover, scoparone also attenuated the production of tumor necrosis factor (TNF)-${\alpha}$, interleukin (IL)-$1{\beta}$ and IL-6 in LPS-stimulated RAW264.7 cells. These results suggest that scoparone decreases the production of the inflammatory mediators such as NO and $PGE_2$ in macrophages by inhibiting iNOS and COX-2 expression.

Agonist-induced Desensitization of Muscarinic Acetylcholine Receptor in Rat Brain

  • Lee, Jong-Hwa;Esam-E.El-Fakahany
    • Archives of Pharmacal Research
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    • 제10권4호
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    • pp.212-218
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    • 1987
  • Intact brain cell aggregates were dissociated from adult rat brains without cerebellum using a sieving technique. This proparation was used to elucidate the binding characteristics of agonist to muscarinic acetylcholine receptors (mAchR) in brain. Incubation of cells with carbamylcholine (carbachol) was shown agonist-induced receptor down-regulation depending on the concentration of agonist, not depending on the incubation time. This effect of carbachol was due to a reduction in the maximal binding capacity ($B_{max}$) to the mAchR without decreasing the affinity of the remaining receptors in incubation at 37.deg.C but was not apparent inincubation at $15^{\circ}}C$In addition, it was abolished when the receptors were blocked by atropine. The decline in ($^3H$)N-methylscopolamine (($^3H$)NMS) binding induced by agonist was reflected as a significant reduction in the receptor density with no change in receptor affinity, suggesting that 'true' receptor down-regulation takes place. Moreover, when the receptors were labeled with the lipophilic antagonist ($^3H$) quinuclidinyl benzilate (($^3H$) QNB) insted of the hydrophilic ligand ($^3H$)NMS, the magnitude of the observed receptor down-regulation was significantly lower in case of the former than the latter. This suggested that exposure of intact brain cells to muscarinic agonists might induce a slight degree of accumulation of receptors in intracellular sites before the receptors are actually degraded.

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Antitumor Activity of the Korean Mistletoe Lectin is Attributed to Activation of Macrophages and NK Cells

  • Yoon, Tae-Joon;Yoo, Yung-Choon;Kang, Tae-Bong;Song, Seong-Kyu;Lee, Kyung-Bok;Her, Erk;Song, Kyung-Sik;Kim, Jong-Bae
    • Archives of Pharmacal Research
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    • 제26권10호
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    • pp.861-867
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    • 2003
  • Inhibitory effect of the lectins (KML-C) isolated from Korean mistletoe (KM; Viscum album coloratum) on tumor metastases produced by murine tumor cells (B16-BL6 melanoma, colon 26M3.1 carcinoma and L5178Y-ML25 lymphoma cells) was investigated in syngeneic mice. An intravenous (i.v.) administration of KML-C (20-50 ng/mouse) 2 days before tumor inoculation significantly inhibited lung metastases of both B16-BL6 and colon 26-M3.1 cells. The prophylactic effect of 50 ng/mouse of KML-C on lung metastasis was almost the same with that of 100 $\mu$ g/mouse of KM. Treatment with KML-C 1 day after tumor inoculation induced a significant inhibition of not only the experimental lung metastasis induced by B16-BL6 and colon 26M3.1 cells but also the liver and spleen metastasis of L5178Y-ML25 cells. Furthermore, multiple administration of KML-C given at 3 day-intervals after tumor inoculation led to a significant reduction of lung metastasis and suppression of the growth of B16-BL6 melanoma cells in a spontaneous metastasis model. In an assay for natural killer (NK) cell activity. i.v. administration of KML-C (50 ng/mouse) significantly augmented NK cytotoxicity against Yac-1 tumor cells 2 days after KML-C treatment. In addition, treatment with KML-C (50 ng/mouse) induced tumoricidal activity of peritoneal macrophages against B16-BL6 and 3LL cells. These results suggest that KML-C has an immunomodulating activity to enhance the host defense system against tumors, and that its prophylactic and therapeutic effect on tumor metastasis is associated with the activation of NK cells and macrophages.

Synthesis, Characterization and in Vitro Identification of $N^7-Guanine$ Adduct of 2-Bromopropane

  • Zhao, Long-Xuan;Kim, Eun-Kyung;Lim, Hyun-Tae;Moon, Yoon-Soo;Kim, Nam-Hee;Kim, Tae-Hyung;Choi, Heesung;Chae, Whigun;Jeong, Tae-Cheon;Lee, Eung-Seok
    • Archives of Pharmacal Research
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    • 제25권1호
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    • pp.39-44
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    • 2002
  • Recently, we have reported that 2-bromopropane might have an immunotoxic potential in rats when exposed for 28 days. In the present studies, the possibility of 2i-deoxyguanosine abduct formation by 2- bromopropane was investigated in vitro to elucidate molecular mechanism of 2-bromopropane-induced immunosuppression. $N^7-Guanine adduct$ of 2'-bromopropane (i.e., $N^7-isopropyl$ guanine) was chemically synthesized and structurally characterized by analysis of UV,$^1H-NMR,{\;}^{13}C-NMR$, COSY and fast atom bombardment mass spectrometry to use as a reference material. Incubation of 2'-deoxyguanosine with an excess amount of 2-bromopropane in PBS buffer solution, pH 7.4, at $37^{\circ}C$ for 16 h, followed by a thermal hydrolysis, produced a detectable amount of $N^7-isopropyl$ guanine by an HPLC and UV analysis. The present results suggest that 2-bromopropane might form a DNA adduct in $N^7-position$ of 2'-deoxyguanosine at 3 Physiological condition.

Developmental Patterns of mST3GaIV mRNA Expression in the Mouse: In Situ Hybridization using DIG-labeled RNA Probes

  • Ji, Min-Young;Lee, Young-Choon;Do, Su-Il;Nam, Sang-Yun;Jung, Kyu-Yong;Kim, Hyoung-Min;Park, Jong-Kun;Choo, Young-Kug
    • Archives of Pharmacal Research
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    • 제23권5호
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    • pp.525-530
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    • 2000
  • mST3GaIV synthesizes ganglioside GM3, the precursor for simple and complex a- and b- series gangliosides, and the expression and regulation of mST3GaIV (CMP-NeuAc: lactosylceramide $\alpha$2,3-sialyltransferase) activity is central to the production of almost all gangliosides, a class of glycosphingolipids implicated in variety of cellular processes such as transmembrane signaling, synaptic transmission, specialized membrane domain formation and cell-cell interactions. To understand the developmental expression of mST3GaIV in mice, we investigated the spatial and temporal expression of mST3GaIV mRNA during the mouse embryogenesis [embryonic (E) days; 19, E11, E13, E15] by in situ hybridization with digoxigenin-labeled RNA probes. All tissues from 19 and E11 were positive for mST3GaIV mRNA. On E13, mST3GaIV mRNA was expressed in various neural and non-neural tissues. In contrast to these, on E15, the telencephalon and liver produced a strong expression of mST3GaIV which was a quite similar to that of E13. In this stage, mST3GaIV mRNA was also expressed in some non-neural tissues. These data indicate that mST3GaIV is differently expressed at developmental stages of embryo, and this may be importantly related with regulation of organogenesis in mice.

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디지털 콘텐츠 저작물의 공정이용 확대에 대한 연구 (A Study on the Extended Fair Use of Copyrighted Digital Contents)

  • 김성묵
    • 문화기술의 융합
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    • 제6권2호
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    • pp.217-222
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    • 2020
  • 디지털 경제에서 저작권 논의는 디지털 저작물의 이용환경 변화와 디지털 기술들의 빠른 발전을 반영해야 한다. 이용자 제작 콘텐츠와 기여활동에 있어서 이용자 저작물 권리의 보장, 양도, 이용에 대한 논의가 필요하다. 디지털 아카이브의 경우 이용허락 범위나 인용 가이드를 명시하는 것이 요청된다. 디지털 복제의 규제에 치우치지 않고 표현의 자유를 늘리고 변형적 가치를 고려하는 것이 필요하다. 디지털 제조에서 사적이용과 공적이용, 공유와 산업간의 긴장이 커질 것이므로 정책적 논의가 진행되어야 한다. 저작자의 권리보호 못지않게 저작물의 공정이용의 범위를 확장하는 방향으로 저작권 해석이 제안될 필요가 있다. 저작물의 공정이용 확대와 구체적인 규정 제시가 창작과 유통을 활성화하고 혁신을 생산적으로 사용하는 데 기여할 것이다.

여성결혼이민자가 체험한 교육문화와 문화적응에 관한 질적 사례연구 (A Qualitative Case Study on the Educational Culture Experienced by Married Immigrant Women and their Acculturation)

  • 김승희
    • 가족자원경영과 정책
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    • 제16권4호
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    • pp.153-170
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    • 2012
  • This study investigated the educational culture experienced by married immigrant women in their own country, as well as their internalizing process of the educational culture in Korea, using a qualitative case study. The purpose of this study was to help married immigrant women solve the problem of acculturation based on their own educational and cultural experiences and to overcome limitations of previous studies, which dealt with the problem of acculturation superficially. Participants were 17 married immigrant women from eight countries who resided in Jeonnam and Jeonbuk provinces. They were selected by the sampling strategy of maximum variation. Data were collected through archives and in-depth interviews and analyzed using within-case analysis and cross-case analysis. The results showed that married immigrant women had no experience of attending private institutions and had good memories of their school life. Based on these kinds of experiences, they criticized Korean mothers who urged their children to attend private institutions. They respected their children's opinions and allowed their children to select private institutions. Despite married immigrant women apparently suffering from acculturation, they educate their children according to their own philosophy and method of education. That is, they solve the problem of acculturation actively and independently. Consequently, in order to help married immigrant women solve the problem of acculturation, it is necessary to respect the difference in the cultures and frame a system that develops the activity and subjectivity of married immigrant women.

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Does Low-Dose Heparin Have a Significant Role in Free Flap Surgery?

  • An, Mun-Young;Shin, Jin Yong;Lee, Young-Keun;Sabbagh, M. Diya;Roh, Si-Gyun;Lee, Nae-Ho
    • 대한두개안면성형외과학회지
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    • 제18권3호
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    • pp.162-165
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    • 2017
  • Background: It is controversial issue that heparin decreases thrombosis for microsurgical anastomosis, and its effective role is under discussion. This study is for proving whether low-dose heparin is preventing thrombosis in free flap reconstruction. Methods: Through chart reviews of 134 patients, using low-dose heparin for free tissue transfer from 2011 to 2016, retrospective analysis was performed. 33 patients received low-dose heparin therapy after surgery. And 101 patients received no-heparin therapy. Complications included flap necrosis, hematoma formation, dehiscence and infection. Results: In no-heparin therapy group, comparing the flap necrosis revealed 16 cases (15.84%). And, flap necrosis was 6 cases (18.18%) in low-dose heparin therapy group. The statistical analysis of flap necrosis rate showed no significant difference (p=0.75). The results showed that there was no significant difference of flap necrosis rate between two groups. Conclusion: In this study, patients in the low-dose heparin group had no significantly lower rates of flap failure compared with no-heparin group. This suggests that low-dose heparin may not prevent thrombosis and subsequent flap failure to a significant extent.