• YAKHAK HOEJI
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• v.42 no.2
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• pp.196-204
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• 1998

The blood-brain barrier (BBB) of rats was modificated opening reversibly by infusing a hyperosmotic solution of arabinose (1.6 molal) into the right external carotid artery. Pre vious studies demonstrated that permeability was increased maxmmally in the first 15 min and remained slightly elevated at 1 hr. As control reference, saline was used. In the present study, to evaluate the effects of osmotic BBB opening on the BBB trasport according to hydrophilic or hydrophobic characteristics of drugs. And the differences of the uptakes of these compounds to right (treated osmotic opening) and left (untreated) hemispheres in same rats were compared each other following injection of 8 mCi per rat of $^{99m}Tc$-ethylene triamine pentaacetic acid (DTPA) as hydrophilic drug or 5mg/kg of phenytoin as hydrophobic drug mto the right external carotid artery of rats between two groups (1.6 molal arabinose vs saline). The uptakes of $^{99m}Tc$-DTPA and phenytoin in the right cerebral hemispheres were increased to about thirty three times and twice rather than those in the left cerebral heimspheres, respectively. And PAs (permeability X capillary surface area) were also increased from a control mean of 2.11${\times}10^{-4}$ (Untreated) to 6.98${\times}10^{-3}\;sec^{-1}$ (treated osmotic opening for $^{99m}Tc$-DTPA and 0.29 to 0.17 $sec^{-1}$ for phenytoin, respectively. From the results of present study, it is noted that osmotic opening of BBB is more effective in the brain delivery of hydrophilic drugs rather than that of hydrophobic drugs.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1994.04a
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• pp.345-345
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• 1994

BBB opening 에 의란 수용성 약물 및 지용성 약물의 뇌혈관 투과 패턴을 알아보기 위해 모델약물로서 수용성 약물인 $^{99}$Tc-DTPA, 지용성 약물인 Pherlytoin을 선택하여 뇌혈관 투과성(PA)의 증가율을 검토하고자 하였다. 랫트의 좌측 외경동맥(left external carotid artery)에 혈류의 역방향으로 PE-50 catheter를 분지점에서 1-2mm 전까지 삽입하고, 1.6 molal L-(+)-arabinosg 고장액 (1580 mOsm)을 0. 12ml/sec의 일정한 속도로 30초간 infusion 한 후. $^{99}$Tc-DTPA 혹은 phenytoin 약물 용액을 대뢰정맥으로 주사하고, 대뢰동맥으로부터 약물 투여전 및 투여후 10, 30초, 1, 1.5, 2, 3. 4, 5. 7, 10분 간격으르 혈액을 채취하였으며. 마지막 채혈후 즉시 단두하여 뇌조직을 취하였다. 채취한 뇌를 좌, 우반구 및 각 부위별로 분리하고 감마 카운터와 HPLC를 이용하여 뇌증농도를 정량하였다. 또한 뇌 실질 조직내 약물량을 구하기 위해 뇌 혈관내에 존재하는 약물양을 보정하였는데, 이때 계산에 필요한 뇌증 혈액부피의 측정은 $^{99}$Tc-albumin을 이용하여 구하였다.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1993.04a
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• pp.177-177
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• 1993

뇌모세혈관내피세포로 구성된 혈액-뇌관문(BBB)은 tight junction으로 구성되어 있을뿐만 아니라 fenestra가 없는 등 BBB가 가진 특성으로 인해 물질 수송에 장벽역할을 하기 때문에 주로 중추신경계 질환시의 약물요법에 많은 제한이 따른다. 따라서 뇌로의 효율적인 약물 송달방법에 대해 많은 연구가 진행중에 있는데 본 연구에서는 BBB의 hyperosmotic opening법을 이용하여 뇌로 잘 수송되지 않는 약물의 뇌송달 방법에 대해 연구하고자 하였다. 먼저 수용성으로 인해 BBB 에 잘 통과하지 않는 물질로 신장 및 뇌영상 촬영시 사용되는 방사성 의약품이 Tc-DTPA를 이용하여, hyperosmotic opening법에 의한 뇌투과 증가정도를 검토하였으며, 실험방법이 확립됨에 따라 뇌암의 항암요법을 위해 뇌로의 투과가 적은 항암제(5-Fluorouracil, 5-FU)의 뇌송달에 대해 본 방법을 적용하여 검토하였다. 실험동물로는 S.D.계 웅성 랫트를 사용하였으며, 실험방법은 다음과 같이 하였다. 랫트의 좌측 외경동맥(left external carotid artery)에 혈류의 역방향으로 혈관 분지점에서 1-2mm 전까지 PE-50 catheter를 삽입하고, 1.6 molal L－(＋)－ arabinose 고장액(1580mOsm)을 0.12ml/sec의 일정한 속도로 30초간 infusion함으로 BBB를 opening 한 다음, 5분 후에 Tc-DTPA를 대퇴 정맥으로 주사하여 0, 10, 30초, 1, 1.5, 2, 3, 4, 5, 7 및 10분 간격으로 대퇴동맥에 설치한 카테타로부터 혈액을 채취하고 마지막 혈액을 취한 후 즉시 단두하여 뇌를 적출하였다. 채취한 뇌를 액체질소에 담근 후 tissue Tek으로 고정하고 autoradiography를 하기 위한 slice와 농도측정을 위해 필요한 부위를 취한 후 감마카운터로 Tc-DTPA의 brain각 부위별 및 혈장농도를 측정하였다. 뇌조직중 혈액부피의 측정은 Tc-albumin를 이용하여 구하였다. 같은 방법으로 5-FU에 대한 실험도 행하였고, 이때 각 혈장 및 조직중의 5-FU함량은 HPLC로 하였다.

• Korean Journal of Environment and Ecology
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• v.30 no.1
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• pp.130-134
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• 2016

How does $CO_2$ affect on the stomatal mechanism? The mechanism of stomatal opening by $CO_2$ is not clear as it is difficult to see $CO_2$ effect on light-induced stomatal opening. Furthermore, stomata may react differently according to the concentration of $CO_2$. The significance of the possible endogenous rhythms must consider to understand on $CO_2$-related response. It is clear that $CO_2$ has an effect on the accumulation of osmotic materials which determines the degree of stomatal apertures because it is known that stomata open in the condition of the reduced $CO_2$ concentration. However, it is not fully understood how $CO_2$ leads to the stomatal opening. It has been thought that $CO_2$ can not affect on the ion fluxes which determines the increase of osmotic potential in guard cells. However, in this study, the changes of guard cell membrane permeability by $CO_2$ have been focused on. There are many reports that $CO_2$ related reactions are dominant when the leaf is exposed to certain a mount of $CO_2$. The hypothesis of the stomatal opening by light is based on the increase of osmotic materials in guard cells including $K^+$, $Cl^-$, sucrose and $malate^{2-}$. It was reported that $CO_2$ induced a big hyperpolarization indicating that $H^+$ was extruded to the cell outside. It was also found that $CO_2$ caused guard cell membrane hyperpolarization in the intact leaf up to 3 or 4 times higher than that of light induced membrane hyperpolarization. These results represent that $CO_2$ can affect on the change of physical characteristics which affects on the change of the membrane permeability.

• The Korean Journal of Ecology
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• v.4 no.3_4
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• pp.59-67
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• 1981

Stomatal resistances of the leaves in Heteromeres arbutifolia and of the stems in Ferocactus acanthodes were studied to estimate active and passive behaviors of the guard cells on a theoretical basis. Active and passive stomatal responses to light and water deficit were observed. When the change rate of existent water due to variation of osmotic potential in the guard cells and the loss rate of transpirational water from the guard cells are $\Delta$wi-$\Delta$wt and leaded to active behaviors for opening and closing stomata. However, when stems of F. acanthodes with stomata closecd under the solar irradiation were covered with black cloth and then taken off, behaviors of the guard cells occurred in the condition of $\Delta$wi<$\Delta$wt and were passive. Under the conditiion of $\Delta$wi<$\Delta$wt due to cutout from stems, passive behaviors of the guard cells in H. arbutifolia and F. acanthodes always occurred in spite of the solar irradiation and darkness, respectively. The transpirational resistance coefficients of the guard cells in stems of F. acanthodes (0.380) and Opuntia bigelovii (0.135) wer emuch higher than in leaves of H. arbutifolia (0.034). Moreover, stomatal opening in stems of F. acanthodes during the daytime could be induced by watering. Those results are interpreted as that since the guard cells in desert Crassulacean acid metabolism (CAM) plants always exist in the state of stomatal opening, nocturnal stomatal opening and daytime stomatal closing are exhibited by passive behaviors of the guard cells in the alternant conditioins of $\Delta$wi>$\Delta$wt and $\Delta$wi<$\Delta$wt, respectively.

• Korean Journal of Environmental Biology
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• v.18 no.2
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• pp.263-268
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• 2000

The effect of $Cd^{2+}$ on stomatal apertures of epidermal strips and intact leaves in Commelina communis L. was investigated. Cadmium stimulated stomatal opening. The stomata, treated with 100 $\mu$M $Cd^{2+}$ opened to a degree of about 8.38 fm, but the stomata, treated with no cadmium opened to 3.74 ${\mu}{\textrm}{m}$. In order to show that there was no mechanical or osmotic impediment preventing the stomata in the epidermal strips, salicylic acid (SA) and abscisic acid (ABA) were used. The treatment of 100 $\mu$M SA and 1 $\mu$M ABA inhibited 14% and 28% of stomatal opening, respectively. Other heavy metals such as $Al^{3+} and Ag^{2+}$ were also used to investigate the effect of the stomatal apertures. The treatment of $Al^{3+} and Ag^{2+}$ also stimulated 19% and 41% of stomatal opening. To understand how cadmium open stomata, the effect of cadmium on the K+ influx into the epidermal strips was investigated. $Cd^{2+}$, SA, ABA inhibited 98%, 28%, 34% of K+ uptake respectively. 3-weeks old Commelina was transferred to and grown in Hoagland solution (0,5 mM $Cd^{2+}$, 10 mM $Cd^{2+}$) for 4 days and stomatal conductance were measured. The treatment of 5 mM $Cd^{2+}$ and 10 mM $Cd^{2+}$ showed about 51% and 70% inhibition of stomatal conductance, respectively Therefore, it could be concluded that stomata in epidermal strips and intact leaves behaved differently and cadmium- stimulated stomatal opening was due to the result of cadmium uptake into the epidermal strips instead of K+. [cadmium, stomata, stomatal conductance]

• Korean Journal of Environmental Biology
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• v.19 no.1
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• pp.1-6
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• 2001

Many researchers have been studied with guard cell protoplasts and detached epidermis as they think that properly stabilized protoplasts and detached epidermis retain many of the properties of intact guard cells. However, some studies have shown that stomata in detached epidermis behave differently, both quantitatively and qualitatively, from those in the intact leaf. Stomata in the intact leaf are very sensitive to environmental factors such as light, $CO_2$ and osmotic stress, but stomata in detached epidermis are less sensitive to these factors than those in the intact leaf. The clearest evidence to suggest the different response between detached epidermis and intact leaf obtained from the experiments with heavy metal, cadmium. 3-weeks old Commelina. communis was transferred to and grown in Hoagland solution in the presence or absence of 5 mM $Cd^{2+}$ for 4 days. The application of $Cd^{2+}$ showed about 70% inhibition of stomatal conductance when measured at various light intensity (100-1,000 $\mu$mole $m^{-2}s^{-1}). However, stomata in detached epidermis floated on an incubation medium containing 100 $\mu$M $Cd^{2+}$ opened to a degree of about 8.38 fm, but the stomata treated with no cadmium opened to 3.74 ${\mu}{\textrm}{m}$. These results were unexpected as the intact leaf grown in a Hoagland solution containing cadmium showed very negative physiological responses. These results showed that stomata in detached epidermis and in the intact leaf could respond reversely. Therefore, it is possible that we now misunderstand how stomata open in real natural condition.