• 제목/요약/키워드: Cell permeability

검색결과 607건 처리시간 0.024초

인체유방암세포의 tight junction 기능 조절을 통한 genistein의 암세포 침윤 억제 효과 (Anti-invasive Activity of Human Breast Carcinoma Cells by Genistein through Modulation of Tight Junction Function)

  • 김성옥;정영기;최영현
    • 생명과학회지
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    • 제19권9호
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    • pp.1200-1208
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    • 2009
  • Tight junctions (TJs)은 인접된 세포 사이의 전해질 및 거대분자 확산 조절에 관여하는 paracellular permeability의 장벽 역할을 한다. 본 연구에서는 MCF-7 및 MDA-MB-231 인체유방암세포에서 대두의 대표적인 생리활성물인 genistein에 의한 암세포의 침윤 억제에서 TJs의 견고성 및 투과성과의 연관성을 조사하였다. 본 연구의 결과에 의하면 genistein에 의한 유방암세포의 증식 억제, 암세포 이동성의 저하 및 침윤성의 억제는 TJs의 증가된 견고성과 연관이 있었으며, 이를 transepithelial electrical resistance의 증가 및 paracellular permeability의 감소로 확인하였다. Genistein은 두 유방암세포에서 TJs의 주요 조절 단백질로서 paracellular transport 조절에 중요한 역할을 하는 claudin-3 및 claudin-4의 발현을 억제시켰다. 그리고 genistein은 암세포의 전이 조절 관련 유전자들인 like growth factor-1 receptor 및 snail의 발현을 억제하였으며, thrombospondin-1 및 E-cadherin의 발현은 증가시켰다. 또한 small interfering RNA를 이용하여 genistein의 유방암세포의 침윤 억제에서 claudin-3단백질의 중요성을 확인하였다. 결론적으로 genistein이 TJs의 견고성 증가를 통하여 암세포의 침윤성을 억제할 수 있었으며, 이 과정에서 아마도 claudin 단백질의 발현 증가가 중요한 역할을 하고 있음을 알 수 있었다. 본 연구의 결과는 genistein이 종양 전이억제를 효과적으로 차단할 수 있음을 보여주는 것이다.

In vitro Transport of Fexofenadine.HCl in Deformable Liposomes Across the Human Nasal Epithelial Cell Monolayers

  • Lin, Hong-Xia;Lee, Chi-Ho;Shim, Chang-Koo;Chung, Suk-Jae;Kim, Dae-Duk
    • Journal of Pharmaceutical Investigation
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    • 제34권6호
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    • pp.483-489
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    • 2004
  • Fexofenadine HCl is non-sedating histamine H1 receptor antagonist that can be used for the treatment of seasonal allergic rhinitis. The objective of this study was to investigate whether the carriers of deformable liposomes can enhance the transepithelial permeability of fexofenadine HCl across the in vitro ALI human nasal monolayer model. Characterization of this model was achieved by bioelectric measurements and morphological studies. The passage 2 and 3 of cell monolayers exhibited the TEER value of $2852\;{\pm}\;482\;ohm\;{\times}\;cm^2$ on 11 days of seeding and maintained high TEER value for 5 days. The deformable liposome of fexofenadine HCl was prepared with phosphatidylcholine (PC) and cholic acid using extruder method. The mean particle size was about 200 nm and the maximum entrapment efficiency of 33.0% was obtained in the formulation of 1% PC and $100\;{\mu}g/ml$ fexofenadine HCl. The toxicity of the deformable liposome to human nasal monolayers was evaluated by MTT assay and TEER value change. MTT assay showed that it has no toxic effect on the nasal epithelial cells in 2-hour incubation when the PC concentration was below 1%. However, deformable liposome could not enhance the transepithelial permeability $(P_{app})$ and cellular uptake of fexofenadine HCl. In conclusion, the in vitro model could be used in nasal drug transport studies and evaluation of transepithelial permeability of formulations.

High-fat Diet Accelerates Intestinal Tumorigenesis Through Disrupting Intestinal Cell Membrane Integrity

  • Park, Mi-Young;Kim, Min Young;Seo, Young Rok;Kim, Jong-Sang;Sung, Mi-Kyung
    • Journal of Cancer Prevention
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    • 제21권2호
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    • pp.95-103
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    • 2016
  • Background: Excess energy supply induces chronic low-grade inflammation in association with oxidative stress in various tissues including intestinal epithelium. The objective of this study was to investigate the effect of high-fat diet (HFD) on intestinal cell membrane integrity and intestinal tumorigenesis in $Apc^{Min/+}$ mice. Methods: Mice were fed with either normal diet (ND) or HFD for 12 weeks. The number of intestinal tumors were counted and biomarkers of endotoxemia, oxidative stress, and inflammation were determined. Changes in intestinal integrity was measured by fluorescein isothiocyanate (FITC)-dextran penetration and membrane gap junction protein expression. Results: HFD group had significantly higher number of tumors compared to ND group (P < 0.05). Blood total antioxidant capacity was lower in HFD group, while colonic 8-hydroxy-2'-deoxyguanosine level, a marker of oxidative damage, was higher in HFD group compared to that of ND group (P < 0.05). The penetration of FITC-dextran was substantially increased in HFD group (P < 0.05) while the expressions of membrane gap junction proteins including zonula occludens-1, claudin-1, and occludin were lower in HFD group (P < 0.05) compared to those in ND group. Serum concentration of lipopolysaccharide (LPS) receptor (CD14) and colonic toll-like receptor 4 (a LPS receptor) mRNA expression were significantly higher in HFD group than in ND group (P < 0.05), suggesting that significant endotoxemia may occur in HFD group due to the increased membrane permeability. Serum interleukin-6 concentration and myeloperoxidase activity were also higher in HFD group compared to those of ND group (P < 0.05). Conclusions: HFD increases oxidative stress disrupting intestinal gap junction proteins, thereby accelerating membrane permeability endotoxemia, inflammation, and intestinal tumorigenesis.

Extrapolation of Hepatic Concentrations of Industrial Chemicals Using Pharmacokinetic Models to Predict Hepatotoxicity

  • Yamazaki, Hiroshi;Kamiya, Yusuke
    • Toxicological Research
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    • 제35권4호
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    • pp.295-301
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    • 2019
  • In this review, we describe the absorption rates (Caco-2 cell permeability) and hepatic/plasma pharmacokinetics of 53 diverse chemicals estimated by modeling virtual oral administration in rats. To ensure that a broad range of chemical structures is present among the selected substances, the properties described by 196 chemical descriptors in a chemoinformatics tool were calculated for 50,000 randomly selected molecules in the original chemical space. To allow visualization, the resulting chemical space was projected onto a two-dimensional plane using generative topographic mapping. The calculated absorbance rates of the chemicals based on cell permeability studies were found to be inversely correlated to the no-observed-effect levels for hepatoxicity after oral administration, as obtained from the Hazard Evaluation Support System Integrated Platform in Japan (r = -0.88, p < 0.01, n = 27). The maximum plasma concentrations and the areas under the concentration-time curves (AUC) of a varied selection of chemicals were estimated using two different methods: simple one-compartment models (i.e., high-throughput toxicokinetic models) and simplified physiologically based pharmacokinetic (PBPK) modeling consisting of chemical receptor (gut), metabolizing (liver), and central (main) compartments. The results obtained from the two methods were consistent. Although the maximum concentrations and AUC values of the 53 chemicals roughly correlated in the liver and plasma, inconsistencies were apparent between empirically measured concentrations and the PBPK-modeled levels. The lowest-observed-effect levels and the virtual hepatic AUC values obtained using PBPK models were inversely correlated (r = -0.78, p < 0.05, n = 7). The present simplified PBPK models could estimate the relationships between hepatic/plasma concentrations and oral doses of general chemicals using both forward and reverse dosimetry. These methods are therefore valuable for estimating hepatotoxicity.

CSLR을 갖는 인셋 급전 마이크로스트립 안테나에 관한 연구 (A Study on Inset Fed Microstrip Antenna Loaded with Complementary Single Loop Resonator)

  • 홍재표;김병문
    • 한국전자통신학회논문지
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    • 제9권8호
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    • pp.921-926
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    • 2014
  • 본 논문에서는 CSLR(Complementary Single Loop Resonator)을 이용한 인셋 급전 마이크로스트립 안테나의 특성에 대해 연구하였다. SLR(Single Loop Resonator) 단일 구조에서 시뮬레이션 셋업 과정을 통해 산란계수로부터 실효투자율을 계산하였으며, 실효투자율이 음의 값을 갖는 주파수에서 SLR 구조의 치수를 선택하였다. 그리고 인셋 급전된 마이크로스트립 안테나의 접지면에 SLR 구조의 쌍대 구조인 CSLR을 $3{\times}3$으로 배열하여 최적 안테나를 설계하였다. 설계한 안테나의 반사손실과 복사패턴을 구하였으며, 공진주파수 2.82 GHz에서 기존의 인셋 급전 안테나와 크기를 비교하면 면적 대비 약 56.8%가 감소하는 결과를 얻었다. 사용된 툴은 3차원 FEM 툴인 Ansoft사의 HFSS를 사용하였다.

Mouse 모델 알레르기 반응에서 삼백초(三白草)가 미치는 영향 (Inhibitory Effect of Saururus chinensis (Lour.) Baill Extracts on Allergy in Mouse Models)

  • 석민희;강경화;최영현;최병태;이용태
    • 동의생리병리학회지
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    • 제19권1호
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    • pp.146-151
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    • 2005
  • We investigated the effect of Saururus chinensis (Lour.) Baill (SCB) on allergy in mice. We conformed compound 48/80-induced mesenteric mast cell degranulation, active systemic anaphylatic shock and histamine release. Also observed acetic acid-induced vascular permeability and anti-dinitrophenyl (DNP) IgE-mediated passive cutaneous anaphylaxis. SCB inhibited mesenteric mast cell degranulation and active systemic anaphylatic shock induced by compound 48/80 dose-dependently. When SCB was pretreated by intra-peritoneal injection, the plasma histamine levels were reduced. SCB also significantly inhibited acetic acid-induced vascular permeability and anti-DNP IgE-mediated passive cutaneous anaphylaxis. In addition, SCB reduced IL-10 mRNA expression of the lung on ovalbumin-induced allergy. These results indicate that SCB inhibits allergy.

두 쌍의 ELC 공진기를 이용한 이중 대역 메타 흡수체의 설계 (Design of Dual-band Metamaterial Absorber using Two Pairs of ELC Resonators)

  • 이형섭;이홍민
    • 한국정보전자통신기술학회논문지
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    • 제5권1호
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    • pp.26-32
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    • 2012
  • 본 논문에서는 4개의 ELC 공진기 구조를 사용하여 메타 흡수체 구조의 단위 셀을 설계하였다. 제안된 구조의 단위 셀의 크기는 $9mm{\times}9mm{\times}2mm$ 이다. 메타 흡수체의 대역폭 확장을 위하여 흡수체 단위 셀은 서로 다른 크기를 갖는 2 쌍의 ECL가 사용되었다. 제안된 흡수체는 전계가 ELC 갭에 수평하게 여기되고 자계가 단위 셀 면에 수직으로 여기 될 경우에 음의 유전율과 음의 투자율 특성을 나타낸다. 제안된 단위 셀은 8.53 GHz, 9.08 GHz에서 공진을 하며 각 주파수에서 90%이상의 흡수율을 갖는다.

과산화수소에 의한 고분자전해질 연료전지 막의 열화 (Degradation of Membrane for PEM Fuel Cell with Hydrogen Peroxide)

  • 김태희;이정훈;박권필
    • 한국신재생에너지학회:학술대회논문집
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    • 한국신재생에너지학회 2006년도 추계학술대회
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    • pp.438-442
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    • 2006
  • The degradation of Nafion membrane by hydrogen peroxide was investigated in polymer electrolyte membrane fuel cell (PEMFC). Degradation tests were carried out in a solution of $10{\sim}30%$ hydrogen peroxide containing 4ppm $Fe^{2+}$ ion which is well known as Fenton's reagent at $80^{\circ}C$ for 48hr. Characterization of degraded membranes were examined through the IR, Water-uptake, Ion exchange capacity, mechanical strength and $H_2$ permeability. After degradation, C-F, S-O and C-O chemical bonds of membrane were broken by radical formed by $H_2O_2$ decomposition. Breaking of C-F bond which is the membrane backbone reduced the mechanical strength of Nafion membrane and hence induced pinholes, resulting in increase of $H_2$ crossover through the membrane. Also the decomposition of C-O and S-O, side chain and terminal bond of membrane, decreased the ion exchange capacity of the membrane.

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SMEDDS를 이용한 난용성 약물의 용출율 향상 (Improvement of Dissolution Rate of Poorly Water Soluble Drug Using Self-microemulsifying Drug Delivery System)

  • 김계현;이윤석;배준호;지상철;박은석
    • Journal of Pharmaceutical Investigation
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    • 제29권1호
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    • pp.37-45
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    • 1999
  • ABSTRACT-A self-microemulsifying drug delivery system (SMEDDS) was developed to enhance the solubility and dissolution rate of poorly water soluble drug, biphenyl dimethyl dicarboxylate, DDB. The system was optimized by evaluating the solubility of DDB and the microemulsion existence range after the preparation of microemulsions with varying compositions of triacetin and surfactant-cosurfactant mixtures (Labrasol as surfactant (S) and the combination of Transcutol, Cremophor RH 40 and Plurol oleique as cosurfactant (CoS)). SMEDDS in this study markedly improved the solubility of DDB in water up to 10 mg/ml and the size of the o/w microemulsion droplets measured by dynamic light scattering showed a narrow monodisperse size distribution with an average diameter less than 50 nm. The microemulsion existing range is increased proportional to the ratio of S/CoS, however, it decreased remarkably as the oil content was more than 20%. In vitro dissolution study of SMEDDS showed a significantly increased dissolution rate of DDB in water (> 12 fold over DDB powder), and SMEDDS also had significantly greater permeability of DDB in Caco-2 cell compared to powders.

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도전성 및 자성 차폐체의 차폐효과 해석과 차폐인수 산정 (Analysis of Shielding Effectiveness and Estimation of Shielding Factor in Conductive and Magnetic Shields)

  • 강대하
    • 조명전기설비학회논문지
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    • 제27권10호
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    • pp.30-40
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    • 2013
  • In this study the method based on flux linkage in cell was introduced in calculation of eddy currents by cell method. According to this method eddy current distribution and the loss can be evaluated and since the shielding effectiveness by flux cancelation of eddy current can be analyzed, this method is applicable to design of conductive shield. And also the formula of shielding factor were so deduced as to be applicable to finite-width infinite-length shielding sheets and infinite-length underground cable shield. These formula are adaptable to magnetic materials as well as conductive materials. As the results of calculation in model shields are follows. In case of finite-width infinite-length shielding sheet, shielding effectiveness increases with increasing of conductivity. In case of infinite-length underground cable shield, the effectiveness become higher with increasing of permeability. Especially the effectiveness is very high in materials with both high conductivity and permeability in underground cable shield.