• Mass Spectrometry Letters
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• 제8권2호
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• pp.34-38
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• 2017

The purpose of this study was to develop a cocktail approach for the measurement of the permeability of marker compounds, caffeine and propranolol (high permeability), ofloxacin (intermediate), atenolol (low), and quinidine (P-glycoprotein substrate), simultaneously. Then we compared the permeability in Caco-2 cells with that in rat intestinal segments. The difference between individual measurement and cocktail approach was less than 20 %, and the permeabilities of these compounds were similar to those previously reported, suggesting that the cocktail transport study and simultaneous drug analysis were successfully developed and validated in this study. Additionally, in the application of this cocktail method, the permeability of five drugs in rat jejunum was similar to that in ileum but different from that in colon, which was measured using the Ussing chamber system. Moreover, permeability in jejunum and ileum was similar to that in Caco-2 cells. In conclusion, the permeability in Caco-2 cells was equivalent to the permeability in rat jejunum and ileum determined with the Ussing system. Therefore, this newly developed cocktail assay and its application to the Ussing system can be a useful tool for robust and rapid screening for site-specific permeability in rat intestine, thus accelerating the prediction of absorption of new chemical entities.

• 제어로봇시스템학회:학술대회논문집
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• 제어로봇시스템학회 1994년도 Proceedings of the Korea Automatic Control Conference, 9th (KACC) ; Taejeon, Korea; 17-20 Oct. 1994
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• pp.747-752
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• 1994

Ussing's flux ratio theorem (1978) reflects a reciprocal relationship behavior between the unidirectional fluxes in asymmetric steady diffusion-convection in a membrane slab. This surprising result has led to many subsequent studies in a wide range of applications, in particular involving linear models of time dependent problems in biology and physiology. Ussing's theorem and its extensions are inherently linear in character. It is of considerable interest to ask to what extent these results apply, if at all, in situations involving, for example, nonlinear reaction. A physiologically interesting situation has been considered by Weisiger et at. (1989, 1991, 1992) and by McNabb et al. (1990, 1991) who studied the role of albumin in the transport of ligands across aqueous diffusion barriers in a liver membrane slab. The results are that there exist reciprocal relationships between unidirectional fluxes in the steady state, although albumin is chemically interacting in a nonlinear way of the diffusion processes. However, the results do not hold in general at early times. Since this type of study first started, it has been speculated about when and how the Ussing's flux ratio theorem fails in a general diffusion-convection-reaction system. In this paper we discuss the validity of Ussing-type theorems in time-dependent situations, and consider the limiting time behavior of a general nonlinear diffusion system with interaction.

• Journal of Photoscience
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• 제3권3호
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• pp.127-132
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• 1996

Calcium has a variety of functions in neuron and muscle cells and blood clotting, especially in the visual system where dark adapted rods cotransport with Na$^+$ into the cell. An influx of Ca$^{2+}$ flows out of the cell through the Na$^+$ - Ca$^{2+}$ exchanger. By using a modified Ussing chamber in order to bring in vivo environment close, we have concluded that Ca$^{2+}$ blocks the activity of guanylate cyclase; in consequence, having an effect on the amplitude of electroretinogram (ERG). We suggest that Ca$^{2+}$ moves between the photoreceptor and the vitreous humor by way of certain Ca$^{2+}$ transport mechanisms. Also, the effect of Zn$^{2+}$ in Ca$^{2+}$ - free ringer solution caused an elevation of amplitude in ERG and a reduction of threshold.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1998년도 Proceedings of UNESCO-internetwork Cooperative Regional Seminar and Workshop on Bioassay Guided Isolation of Bioactive Substances from Natural Products and Microbial Products
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• pp.137-137
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• 1998

Stability, efficacy, absorption and toxicity of a new nasal spray formulation including salmon calcitonin were studied in the laboratory animals. After the effects of many excipients on the stability of salmon calcitonin were evaluated using HPLC system, we selected taurine. Our experimental composition of salmon calcitonin contains taurine as a stabilizer and HPMC (hydroxypropylmethyl cellulose) as an adhesive polymer. After intranasal administration of salmon calcitonin formulations, Mia$\^$(R)/, Men$\^$(R)/ and experimental composition, 22 IU to rats, the reduction percentages of calcium concentration in plasma (ΔD%) were 16.3%, 12.9% and 20.8%, respectively. After intranasal administration of Mia$\^$(R)/, Men$\^$(R)/ and experimental composition to rats, C$\sub$MAX/ (205${\pm}$161, 244${\pm}$117, and 330${\pm}$202 pg/$m\ell$, respectively) and AUC (41585${\pm}$22070, 41191${\pm}$19125, and 63357${\pm}$43126 pg. min/$m\ell$, respectively) were calculated. The permeation coefficients 10$\^$-7/,cm/sec) of salmon calcitonin in Mia$\^$(R)/, Men$\^$(R)/ and experimental composition using Ussing chamber with rabbit nasal mucosa were 4.7${\pm}$1.5, 0.75${\pm}$0.4 and 5.3${\pm}$1.1, respectively. The experimental composition with taurine and HPMC was proved to be excellent because it improved the stability of salmon calcitonin and inhanced the absorption of salmon calcitonin and was not irritative to the nasal mucosa.

• 대한약리학회지
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• 제22권1호
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• pp.24-33
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• 1986

본 연구에서는 개구리(Rana nigromaculata)의 피부에 있어서 전위차(PD), 단락전류(SCC) 및 total skin conductance(TSC)에 미치는 제종 adrenergic agonist 및 그 차단제의 영향을 관찰하여 개구리 피부에 adrenoceptors의 존재를 확인하고 Na 수송에 있어 그들의 역할을 구명코자 하였다. 1.Norepinephrine(NE, $6{\times}10^{-8}-6{\times}10^{-5}M$), phenylephrine($PE,5{\times}10^{-6}-5{\times}10^{-4}M$)의 PD 및 epinephrine(Epi, $5.5{\times}10^{-7}-5.5{\times}10^{-5}M$)의 PD 및 SCC 증가효과는 약물의 투여농도에 비례하였으며, Epi의 최대효과는 NE나 PE의 것보다 약하였다. 2. 이러한 PD 및 SCC의 증가효과는 alpha 1 adrenoceptor 차단체인 prazosin $2{\times}10^{-6}M$에 의해서 억제되었으며, 특히 Epi의 증가효과는 불가역성 alpha receptor 차단제인 phenoxybenzamine $3.3{\times}10^{-5}M$에 의하여 완전히 차단되며 대량의 Epi에 의해서는 PD 및 SCC의 감소를 초래하였다. 3. Beta adrenoceptor agonist인 isoproterenol$(5{\times}10^{-7}-5{\times}10^{-6}M)$에 의해 농도증가에 비례한 PD 및 SCC의 감소가 일어났으며, 이는 선택적 bete receptor 차단제인 propranolol $4{\times}10^{-6}M$에 의해 차단되었다. 또한 Epi의 PD 및 SCC 증가효과는 propranolol $4{\times}10M$에 의하여 강화됨을 볼 수 있었다. 4. Alpha 2 adrenoceptor agonist인 clonidine 및 guanabenz도 PD 및 SCC의 증가를 가져왔으며 이러한 효과는 alpha 2 receptor 차단제인 yohimbine에서 보다 Alpha 1 receptor 차단제인 prazosin에 의해 더 잘 억제되었다. 이상 실험의 결과 개구리 복부피부에도 포유동물에서와 같이 adrenergic alpha 및 beta receptor가 존재하며 alpha receptor는 PD 및 SCC의 증가를, beta receptor는 PD 및 SCC의 감소를 매개하여, 개구리 피부의 Na 수송에 있어 adrenergic system이 중요한 조절작용을 하고 있음을 알 수 있었다. 그러나 여기에 관여하는 alpha receptor는 다른 포유류에서와 같이 alpha 1 및 alpha 2 adrenoceptor로 구분할 수는 없었다.