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Combination of Vitamin C and Rutin on Neuropathy and Lung Damage of Diabetes Mellitus Rats
Sohn, Uy-Dong,Je, Hyun-Dong,Shin, Chang-Yell,Park, Sun-Young,Yim, Sung-Hyuk,Kum, Chan,Huh, In-Hoi,Kim, Jin -Hak The Pharmaceutical Society of Korea 2002 Archives of Pharmacal Research Vol.25 No.2
We investigated the role of vitamin C or rutin on neuropathy and lung damage of diabetic mellitus(DM) rats. Norepinephrine content was significantly decreased in sciatic nerves of DM rats compared with non-DM controls but vitamin C had no effect on decreases of norepinephrine. 2,4-dinitrophenylhydrazine (DNPH) incorporation, which is biomarker of protein oxidation, was increased in sciatic nerve of DM rats as compared with normal control. However, vitamin C had no effects on increases of DNPH incorporation . We measured the content of conjugated dienes (CD) as a biomarker of lipid oxidation in sciatic nerve. CD was increased in DM as compared with normal control, Vitamin C or rutin had no effects on increases of CD. However, Rutin plus vitamin C significantly decreased the content of CD as compared with CIM rats. In lung of DM rats, DNPH incorporation or CD was increased as compared with normal control. Vitamin C or Rutin had no effects on increases of CD However, Rutin plus vitamin C significantly decreased the content of DNPH incorporation or CD in lung tissue. Vitamin C caused marked pathological changes such as the increases of parenchyma and the thickening of alveolar septa in the lung of DM. Rutin had protective effects on the pathological changes in the lung of DM rats. In conclusion, Vitamin C had no effects on oxidative parameter, such as DNPH incorporation or CD, and on the decreases of norepinephrine content in DM rats. Vitamin C caused the marked pathological changes in the lung of DM rats but rutin had protective efforts against the pathological changes.
Streptozotocin으로 유발된 당뇨병쥐의 신경전도속도에 대한 Evening primrose oil (EPO), Vit.C, Vit.E의 약물효과
신창열,류정수,김학림,강봉수,손의동,허인회 중앙대학교 약학연구소 1997 약학 논총 Vol.11 No.-
The effects of evening primrose oil (EPO). Vit.C and Vit.E on nerve conduction velocity (NCV) in streptozotocin -induced diabetic rats were investigated. 5 weeks- diabetes caused 27±0.5 % reduction in sciatic motor conduction velocity as compared with normal control. Dietary supplement of 5% EPO. 125mg/kg Vit.C. and lg/kg Vit.E prevented significantly the development of the motor nerve conduction velocity deficit about 21±0.5, 21±0.5, 26±0.5% respectively. The total serum cholesterol and triglyceride were decreased by administration 5% EPO. Vit.C, and Vit.E as compared with diabetic control. However, the serum glucose was not decreased by administration 5% EPO. 125mg/kg Vit.C but the serum glucose was decreased by administration lg/kg Vit.E as compared with diabetic control.
Shin, Chang-Yell,Jung, Mi-Young,Lee, In-Ki,Son, Mi-Won,Kim, Dong-Sung,Lim, Joong-In,Kim, Soon-Hoe,Yoo, Moo-Hi,Huh, Tae-Lin,Sohn, Young-Taek,Kim, Won-Bae The Pharmaceutical Society of Korea 2004 Archives of Pharmacal Research Vol.27 No.1
DA-11004 is a synthetic, potent NADP-dependent isocitrate dehydrogenase (IDPc) inhibitor where $IC_{50}$ for IDPc is 1.49 $\mu$M. The purpose of this study was to evaluate the effects of DA-11004 on the high fat high sucrose (HF)-induced obesity in male C57BL/6J mice. After completing a 8-week period of experimentation, the mice were sacrificed 1hr after the last DA-11004 treatment and their blood, liver, and adipose tissues (epididymal and retroperitoneal fat)were collected. There was a significant difference in the pattern of increasing body weight between the HF control and the DA-11004 group. In the DA-11004 (100 mg/kg) treated group the increase in body weight significantly declined and a content of epididymal fat and retroperitoneal fat was also significantly decreased as opposed to the HF control. DA-11004 (100 mg/kg) inhibited the IDPc activity, and thus, NADPH levels in plasma and the levels of free fatty acid (FFA) or glucose in plasma were less than the levels of the HF control group. In conclusion, DA-11004 inhibited the fatty acid synthesis in adipose tissues via IDPc inhibition, and it decreased the plasma glucose levels and FFA in HF diet-induced obesity of C57BL/6J mice.
Shin, Chang Yell,Jung, Mi Young,Lee, In Ki,Son, Miwon,Kim, Dong Sung,Lim, Joong In,Kim, Soon Hoe,Yoo, Moohi,Huh, Tae Lin,Sohn, Young Taek,Kim, Won Bae 德成女子大學校 藥學硏究所 2004 藥學論文誌 Vol.15 No.1
DA-11004 is a synthetic, potent NADP-dependent isocitrate dehydrogenase (IDPc) inhibitor where IC_(50) for IDPc is 1.49 μM. The purpose of this study was to evaluate the effects of DA-11004 on the high fat high sucrose (HF)-induced obesity in male C57BL/6J mice. After completing a 8-week period of experimentation, the mice were sacrificed 1hr after the last DA-11004 treatment and their blood, liver, and adipose tissues (epididymal and retroperitoneal fat) were collected. There was a significant difference in the pattern of increasing body weight between the HF control and the DA-11004 group. In the DA-11004 (100 ㎎/㎏) treated group the increase in body weight significantly declined and a content of epididymal fat and retroperitoneal fat was also significantly decreased as opposed to the HF control. DA-11004 (100 mg/㎏) inhibited the IDPc activity, and thus, NADPH levels in plasma and the levels of free fatty acid (FFA) or glucose in plasma were less than the levels of the HF control group. In conclusion, DA-11004 inhibited the fatty acid synthesis in adipose tissues via IDPc inhibition, and it decreased the plasma glucose levels and FFA in HF diet-induced obesity of C57BL/6J mice.
Chang Yell Shin,Mi Young Jung,In Ki Lee,Miwon Son,Dong Sung Kim,Joong In Lim,Soon Hoe Kim,Moohi Yoo,Tae Lin Huh,Young Taek Sohn,Won Bae Kim 대한약학회 2004 Archives of Pharmacal Research Vol.27 No.1
DA-11004 is a synthetic, potent NADP-dependent isocitrate dehydrogenase (IDPc) inhibitor where IC50 for IDPc is 1.49 mM. The purpose of this study was to evaluate the effects of DA- 11004 on the high fat high sucrose (HF)-induced obesity in male C57BL/6J mice. After completing a 8-week period of experimentation, the mice were sacrificed 1hr after the last DA- 11004 treatment and their blood, liver, and adipose tissues (epididymal and retroperitoneal fat) were collected. There was a significant difference in the pattern of increasing body weight between the HF control and the DA-11004 group. In the DA-11004 (100 mg/kg) treated group the increase in body weight significantly declined and a content of epididymal fat and retroperitoneal fat was also significantly decreased as opposed to the HF control. DA-11004 (100 mg/ kg) inhibited the IDPc activity, and thus, NADPH levels in plasma and the levels of free fatty acid (FFA) or glucose in plasma were less than the levels of the HF control group. In conclusion, DA-11004 inhibited the fatty acid synthesis in adipose tissues via IDPc inhibition, and it decreased the plasma glucose levels and FFA in HF diet-induced obesity of C57BL/6J mice.
Cyclic AMP Dependent Down Regulation in the Relaxation of Smooth Muscle Cells of Cat Esophagitis
Shin, Chang-Yell,Lee, Yul-Pyo,Song, Hyun-Ju,Je, Hyun-Dong,Sohn, Uy-Dong 대한약학회 2007 Archives of Pharmacal Research Vol.30 No.6
We investigated whether the signal mechanism for relaxation may be affected by inflammation of the cat esophagus. Acute esophagitis was induced by perfusion with 0.1N HCI at a rate of 1mL/min for 45 min over three consecutive days. We then isolated esophageal smooth muscle cells by enzymatic digestion with collagenase. We pre-contracted the isolated smooth cells with acetylcholine (ACh) (10$^{-5}$ M) and compared the agonist-induced relaxation of pre-contracted normal cells with those of esophagitic cells. Vasoactive intestinal polypeptide (VIP)caused a dose-dependent relaxation in normal cells, and this curve was down shifted in esophagitic cells. Sodium nitroprusside (SNP) or SIN-1 (NO donor) produced dose-dependent relaxation in normal cells, which was not affected by esophagitis. 8-Br-cGMP (a cGMP analog) also induced dose-dependent relaxation to a similar extort in both normal and esophagitic cells. Forskolin (a cAMP activator) or db-cAMP (a CAMP analog) produced dose-dependent relaxation in normal cells, and this relaxation curve was down shifted in esophagitic cells. Western blotting was used to determine what subtype of adenylyl cyclase was involved in the CAMP pathway. Western blot analysis of homogenates derived from esophageal smooth muscle using antibodies against adenylyl cyclase types II, III, IV and V/VI revealed the presence of type V and/or type VI only. This result suggests that relaxation via a cAMP-dependent pathway rather than a cGMP dependent-pathway is down regulated in cat acute esophagitis. This subsensitivity of the cAMP related pathway may be related to the activity of adenylyl cyclase V/VI.
Shin, Chang Yell,Kim, Hae-Sun,Cha, Kwang-Ho,Won, Dong Han,Lee, Ji-Yun,Jang, Sun Woo,Sohn, Uy Dong The Korean Society of Applied Pharmacology 2018 Biomolecules & Therapeutics(구 응용약물학회지) Vol.26 No.3
A previous study in humans demonstrated the sustained inhibitory effects of donepezil on acetylcholinesterase (AChE) activity; however, the effective concentration of donepezil in humans and animals is unclear. This study aimed to characterize the effective concentration of donepezil on AChE inhibition and impaired learning and memory in rodents. A pharmacokinetic study of donepezil showed a mean peak plasma concentration of donepezil after oral treatment (3 and 10 mg/kg) of approximately $1.2{\pm}0.4h$ and $1.4{\pm}0.5h$, respectively; absolute bioavailability was calculated as 3.6%. Further, AChE activity was inhibited by increasing plasma concentrations of donepezil, and a maximum inhibition of $31.5{\pm}5.7%$ was observed after donepezil treatment in hairless rats. Plasma AChE activity was negatively correlated with plasma donepezil concentration. The pharmacological effects of donepezil are dependent upon its concentration and AChE activity; therefore, we assessed the effects of donepezil on learning and memory using a Y-maze in mice. Donepezil treatment (3 mg/kg) significantly prevented the progression of scopolamine-induced memory impairment in mice. As the concentration of donepezil in the brain increased, the recovery of spontaneous alternations also improved; maximal improvement was observed at $46.5{\pm}3.5ng/g$ in the brain. In conclusion, our findings suggest that the AChE inhibitory activity and pharmacological effects of donepezil can be predicted by the concentration of donepezil. Further, $46.5{\pm}3.5ng/g$ donepezil is an efficacious target concentration in the brain for treating learning and memory impairment in rodents.
DA-7911, $^{188}Rhenium-tin$ Colloid, as a New Therapeutic Agent of Rheumatoid Arthritis
Shin, Chang-Yell,Son, Miwon,Ko, Jun-Il,Jung, Mi-Young,Lee, In-Ki,Kim, Soon-Hoe,Kim, Won-Bae,Jeong, Jae-Min,Song, Yeong-Wook The Pharmaceutical Society of Korea 2003 Archives of Pharmacal Research Vol.26 No.2
Radiation synovectomy is one of the most useful methods for treating patients with refractory synovitis because of its convenience, long-term effects, repeatability and the avoidance of surgery. In this study, we investigated the toxicity, stability and biodistribution of a rhenium-188 ($^{188}$Re)-tin colloid to evaluate its suitability as a synovectomy agent. Twenty four hours after injecting the $^{188}$Re-tin colloids (74 KBq/0.1 mL) into the tail vein of ICR mice, most of the $^{188}$Retin colloidal particles was found in the lungs. In addition, there were no particle size changes at either room temperature or at $37^{\circ}C$ after injecting the $^{188}$Re-tin colloids in human plasma and synovial fluid. In vitro stability tests showed that the $^{188}$Re-tin colloid remained in a colloidal form without a critical size variation over a 2-day period. We investigated the leakage of $^{188}$Retin colloids from the intraarticular injection site with gamma counting in New Zealand white rabbits. The $^{188}$Re-tin colloids (55.5 MBq/0.15 mL) were injected at the cavum articular and the mean retention percentage of the $^{188}$Re-tin colloid was 98.7% for 1 day at the injection site, which suggests that there was neither change in the particle size nor leakage at the injection sites. In the biodistribution study with the SD rats, the liver showed the highest radioactivity (0.0427% ID/organ) except for the injected knees (99.49%). In the SD rats, mild toxicities including the skin or a synovium inflammation were observed as a result of a radioactivity of 15 mCi/kg at the intraarticular injection site. However, there was no systemic toxicity. In the Ovalbumin (OVA)-induced arthritic rabbits, the $^{188}$Re-tin colloid improved the macroscopic, the histological score and reduced the knee joint diameter when compared to the arthritic control. In conclusion, a $^{188}$Re-tin-colloid is considered as a strong candidate for radiation synovectomy with a superior efficacy and safety.