• Proceedings of the Korean Society of Applied Pharmacology
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• 2003.11a
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• pp.107-107
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• 2003

The purpose of this study is to examine that the efflux transport system for choline from brain to blood is present at the blood-brain barrier (BBB) using brain efflux index (BEI) method. ［$^3$H］Choline was microinjected into parietal cortex area 2 (Par2) region of rat brain, and was eliminated from the brain with an apparent elimination half life of 45 min. The BBB efflux clearance of ［$^3$H］choline was 0.12 $m\ell$/min/g brain, which was calculated from the efflux rate constant (1.5${\times}$10$\^$-2/ min$\^$-1/) and the distribution volume in the brain slice (8.1 $m\ell$/g brain). This process was saturable and significantly inhibited by various organic cationic compounds including hemicholinium-3, tetraethylammonium chloride (TEA) and verapamil, by antioxidant, ${\alpha}$-phenyl-n-tert-butyl nitrone (PBN), and by Alzheimer's disease therapeutics, such as acetyl $\ell$-carnitine and tacrine. In conclusion, this finding is the first direct in vivo evidence that choline is transported from brain to the blood across the BBB via a carrier-mediated efflux transport process.

• Journal of Pharmaceutical Investigation
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• v.25 no.3
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• pp.7-20
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• 1995

Taurine, a ${\beta}-amino$ acid, plays an important role as a neuromodulator and is necessary for the normal development of the brain. Since de novo synthesis of taurine in the brain is minimal and in vivo studies suggest that taurine dose not cross the blood-brain barrier, we examined whether the choroid plexus, the blood-cerebrospinal fluid (CSF) barrier, plays a role in taurine transport in the central nervous system. The uptake of $[^3H]-taurine$ into ATP depleted choroid plexus from rabbit was substantially greater in the presence of an inwardly directed $Na^+$ gradient taurine accumulation was negligible. A transient in side-negative potential gradient enhanced the $Na^+-driven$ uptake of taurine into the tissue slices, suggesting that the transport process is electrogenic, $Na^+-driven$ taurine uptake was saturable with an estimated $V_{max}$ of $111\;{\pm}\;20.2\;nmole/g/15\;min$ and a $K_M\;of\;99.8{\pm}29.9\;{\mu}M$. The estimated coupling ratio of $Na^+$ and taurine was $1.80\;{\pm}\;0.122.$ $Na^+-dependent$ taurine uptake was significantly inhibited by ${\beta}-amino$ acids, but not by ${\alpha}-amino$ acids, indicating that the transporter is selective for ${\beta}-amino$ acids. Since it is known that the physiological concentration of taurine in the CSF is lower than that in the plasma, the active transport system we characterized may face the brush border (i.e., CSF facing) side of the choroid plexus and actively transport taurine out of the CSF. Therefore, we examined in vivo elimination of taurine from the CSF in the rat to determine whether elimination kinetics of taurine from the CSF is consistent with the in vitro study. Using a stereotaxic device, cannulaes were placed into the lateral ventricle and the cisterna magna of the rat. Radio-labelled taurine and inulin (a marker of CSF flow) were injected into the lateral ventricle, and the concentrations of the labelled compounds in the CSF were monitored for upto 3 hrs in the cisterna magna. The apparent clearance of taurine from CSF was greater than the estimated CSF flow (p<0.005) indicating that there is a clearance process in addition to the CSF flow. Taurine distribution into the choroid plexus was at least 10 fold higher than that found in other brain areas (e. g., cerebellum, olfactory bulb and cortex). When unlabelled taurine was co-administered with radio-labelled taurine, the apparent clearance of taurine was reduced (p<0.0l), suggesting a saturable disposition of taurine from CSF. Distribution of taurine into the choroid plexus, cerebellum, olfactory bulb and cortex was similarly diminished, indicating that the saturable uptake of taurine into these tissues is responsible for the non-linear disposition. A pharmacokinetic model involving first order elimination and saturable distribution described these data adequately. The Michaelis-Menten rate constant estimated from in vivo elimination study is similar to that obtained in the in vitro uptake experiment. Collectively, our results demonstrate that taurine is transported in the choroid plexus via a $Na^+-dependent,saturable$ and apparently ${\beta}-amino$ acid selective mechanism. This process may be functionally relevant to taurine homeostasis in the brain.

• Journal of the Korean Society of Food Science and Nutrition
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• v.43 no.8
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• pp.1139-1147
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• 2014

We investigated whether or not Schisandra chinensis (SC), a traditional herbal medicine, has protective effects against alcohol-induced fatty liver and blood alcohol clearance. Two tests focused on acute intoxication and chronic ethanol treatment were carried out. For the chronic ethanol treatment test, rats were fed ethanol by intragastric administration everyday for 8 weeks to induce alcoholic fatty liver. Ethanol treatment significantly increased blood alcohol concentration at 90 min after acute ethanol intoxication. Compared with the two ethanol-treated groups, rats administered ethanol along with SC extracts showed an approximately 13% increased blood alcohol clearance rate at 360 min. Chronic ethanol treatment significantly increased serum and hepatic triglyceride (TG) levels, and caused fatty degeneration of liver. Ethanol treatment also elevated the serum total-cholesterol (TC) level. However, after feeding of ethanol plus SC extracts, ethanol-induced elevation of hepatic TG levels reversed, whereas elevation of serum TG and TC levels was not observed after treatment with SC extracts. Ethanol treatment significantly increased ${\gamma}$-GT, aspartate aminotransferase, and alanine aminotransferase activities after 8 weeks. Compared with the ethanol-fed group, rats administered ethanol plus SC extracts for 4 weeks showed attenuated fatty degeneration as well as decreased hepatic function test values. SC administration also significantly increased intracellular lipid accumulation in hepatocytes and reduced steatosis score and hepatic TG levels, as measured by biochemical and histolopathological analyses. Our results indicate that the protective effects of SC are accompanied by a significant decrease in hepatic TG levels, thereby suggesting SC has the ability to prevent ethanol-induced fatty liver, by reducing hepatic TG and enzyme levels in alcoholic rats.

• Korean Journal of Clinical Pharmacy
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• v.22 no.3
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• pp.228-233
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• 2012

Purpose: The purpose of this study was to elucidate the effect of dissolved oxygen in alcohol to blood pressure of healthy persons. Methods: Subjects (n=30) were randomized in a double blind crossover study to receive 120 mL, 240 mL, 360 mL of alcohol (Korean spirit, 19.59 v/v%, dissolved oxygen is 8 ppm and 20 ppm). Blood alcohol concentration (BAC) and blood pressure were measured applying Lion SD-400 Alcolmeter$^{(R)}$ Breathalyser and Tensoval duo control. Pharmacokinetic parameters ($C_{max}$, $T_{max}$, $AUC_{last}$, $K_{el}$, $V_d$, Clearance) were calculated using Winnonlin$^{(R)}$ program. The difference of parameters and values were analysed by student t-test using Microsoft$^{(R)}$ Excel program. Results: The $AUC_{last}$ values of 8 ppm group and 20 ppm group in 240 ml administration were $6.15{\pm}2.60cg{\cdot}min/ml$, $5.33{\pm}1.84cg{\cdot}min/ml$ (p<0.05) and those in 360 mL were $11.93{\pm}5.70cg{\cdot}min/ml$, $10.33{\pm}4.60cg{\cdot}min/ml$ (p < 0.01), respectively. Thus, the $AUC_{last}$ was significantly decreased. On the other hands, there was a significant change in systolic blood pressure (SBP) after alcohol administration. All measured value after 360 mL of alcohol administration was significantly decreased (p < 0.01). Conclusions: The dissolved oxygen in alcoholic beverage has no effect on blood pressures but the alcohol administration has an effect on blood pressure. Thus, SBP can be used as a biomarker of alcohol administration and utilized in PK/PD modeling of alcohol.

• The Journal of Korean Medicine
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• v.18 no.1
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• pp.456-469
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• 1997

The cerebral infarction arised from occulsion of cerebral artery has a high mortality rate and fatal sequelae. Sohabhyangwon(蘇合香元) is generally regarded to have a effect of walking up the patient from unconsiousness and promoting the flow of Qj(氣) by warming channel. METHOD The purpose of this study is to find out the effections of Sohabhyangwon(蘇合香元) on regional cerebral blood flow and relative cerebral infarction area in the experimentally induced infartion in rats In this experiment, 12 Spraque-Dawley rats weighting 280-350g were used. Cerebral ischemia induced by intraluminal suture technique of Kozumi's and Zea-Longer's method. $Co_{2},\;O_2$, pH, arterial blood pressure in rats were checked by Blood Gas Analyzer every 30 minutes for 2 hours. And regional cerebral blood flow were checking by hydrogen clearance technique, cerebral infarcted area was megsured by Image Analysis System. RESULTS 1. During the experiment, $CO_{2},\;O_2$, pH, arterial blood pressure in rats had no change in both sample group and control group. 2. Cortical cerebral blood flow decreased at same rate in both sample group and control group after inducing cerebral infarction. 3. On comparison of relative cerebral infarcted area, Sohabhyangwon(蘇合香元) perfused group showed a significant decrease. CONCLUSION According to the result above, Sohabhyangwon has a protection effect on cranial nerve and-has no effect on cerebral blood flow.

• The Journal of Korean Medicine
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• v.30 no.3
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• pp.106-110
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• 2009

Objective : To study the Oriental Medicine-based strategies or therapeutics for chronic HBV infection. Methods : A chronic HBV carrier was treated with only oriental therapies. Then, serum biochemical parameters were serially chased, and change of HBV-DNA level was evaluated. Result : The biochemical indicators (AST, ALT, gamma-GTP, bilirubin) fluctuated during the treatment period. After one episode of drastic elevation of serum aminotransferase, HBV-DNA disappeared from the blood along with normalization of biochemical parameters within two years of beginning treatment. Conclusion : Oriental Medicine-based therapeutics could be an alternative strategy against chronic infection of HBV.

• 대한핵의학회:학술대회논문집
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• 1970.10a
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• pp.90.3-91
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• 1970

• Journal of Pharmaceutical Investigation
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• v.10 no.3
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• pp.27-32
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• 1980

This paper was to investigate the biovailability of antipyrine, ampicillin and protein binding in pathological rats and rabbits pretreated with typhoid vaccine. The results are as follows: The absorption of antipyrine and ampicillin respectively were reduced in rats pretreated with typhoid vaccine as compared with those of normal rats. Especially absorption of ampicillin was more decreased than those of antipyrine. The blood level of antipyrine in severe state was decreased but in mild state. Blood level of ampicillin was decreased in mild state as well as in severe state. Relative bioavailability of antipyrine and ampicillin were mostly decreased in rabbits pretreated with typhoid vaccine except that of antipyrine in mild state. Renal clearance of antipyrine was not affected, but that of ampicillin was apt to increase. Protein binding of antipyrine and ampicillin were decreased by high concentration of typhoid vaccine.

• Journal of Chest Surgery
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• v.28 no.10
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• pp.892-899
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• 1995

Pancreatitis is a known complication of cardiac surgery with cardiopulmonary bypass. Although ischemia is believed to be a factor, the exact cause of pancreatitis after cardiopulmonary bypass remains unknown.We prospectively studied 67 consecutive patients undergoing cardiac surgery with cardiopulmonary bypass for evaluation of the pancreatic injury after cardiopulmonary bypas. Serial measurement of amylase level in serum and urine was done postoperatively. Hyperamylasemia was detected in 15 patients[22.4% , of whom no patient had pancreatitis. There was no significant difference between serum amylase level and parameters such as cardiopulmonay bypass time, aortic cross clamp time, mean blood pressure, rectal temperature, flow rate, and use of circulatory arrest during cardiopulmonary bypass. Hyperamylasuria was detected in 8 patients[11.9% , and urine amylase level was elevated significantly in the groups with prolonged cardiopulmonary bypass, mean blood pressure more than 40mmHg, and rectal temperature more than 20 $^{\circ}$C. We recommend that serum amylase level and/or amylase-creatinine clearance ratio is measured for ealy detection and management of pancreatitis after cardiopulmonary bypass.

• Proceedings of the Korean Society of Toxicology Conference
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• 2002.11b
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• pp.194-194
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• 2002

Interferon has therapeutic potential for a wide range of infectious and proliferous disorders such as chronic hepatitis C. However, it has drawbacks such as relatively short serum half-life and rapid clearance like other therapeutic proteins. The attachment of a polyethylene glycol (PEG) moiety to interferon is considered as one of the most promising solutions for its ability to extend the plasma residence time.(omitted)