• Journal of Acupuncture Research
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• v.18 no.1
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• pp.76-87
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• 2001

Objective : Zusanli(ST36) and Hoku(Li4) are analgesic acupuncture points frequently used for acupuncture in Oriental medicine. The present study was conducted to see the antinociceptive effects produced by electroacupuncture combined two frequencies(Low, High) and two different acupuncture points(LI4, ST36) in the rat tail flick test. Method : In this study the Rats (Sprague-Dawley, 250-300g) were partially anesthetized with thiopental sodium(40mg/kg, i.p.). The basal reaction time for the tail-flick was 3${\pm}$0.5 sec. Low frequency(3Hz, 5V, biphasic) and high frequency(100Hz, 5V, biphasic) were applied to the inserted needle for the period of insertion(twenty minutes). Experimental groups are divied as follow; a) electroacupuncture stimulation groups at Hoku with or high frequency(L-EA, H-EA), b) electroacupuncture stimulation groups at Zusanli with low or high frequency(1-EA, h-EA), c) low frequency at Hoku and Zusanli(LIEA), d) low frequency at Hoku and high frequency at Zusanli(LhEA), e) high frequency at Hoku and low frequency at Zusanli(HIEA), f) high frequency at Hoku and Zusanli(HhEA) Results : The individual stimulation at either Hoku or Zusanli with low frequency has stronger and longer analgesic effect than high frequency stimulation. In addition, the combined stimulation at Hoku and Zusanli with low frequency has superior effect to individual stimulation with low frequency. LhEA and LIEA have superior effect to other stimulation groups among the combined groups. In order to determine the involvement of opioid system on the different antinociceptive effects, Naloxone, an opioid antagonist, was used in the combined groups. LIEA is the most sensitive when naloxone was administrated among study groups. HhEA is the least sensitive in the administration of naloxone. Conclusion : From results, this study confirmed that the opioid system is involved in analgesic effect of low frequency stimulation of acupuncture point, and we also can suggest the stronger analgesic effect of combining stimulation points is due to the theory of spatial summation in the nervous system.

• Journal of Oral Medicine and Pain
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• v.32 no.1
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• pp.35-43
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• 2007

This study was conducted to investigate the preventing effects of OPB (water extracts of Rehmannia glutinosa Libosch and Eleutherococcus senticosus Max) on bone loss in ovariectomized rats. Twenty Sprague Dawley rats of 13 week-old were divided into two groups: control group (ovariectomized, OVX)) and experimental group (OVX + OPB). The preventing effects of OPB on bone loss, OPB were fed with 100 mg OPB/kg body weight from 3 days after ovariectomization. The duration of the treatment period was 8 weeks. All bone mineral density, bone mineral content indices and bone strength indices measured by peripheral quantitative computerized tomography (pQCT) and serum bone marker assessment were carried out at end of experiment. pQCT scanning showed that OVX induced a significant decrease in cancellous bone mineral density in the proximal tibia ($-29.8{\pm}3.0%$). These decreases were significantly prevented by the administration of OPB 100 mg/kg ($-21.4{\pm}2.3%$. p<0.05). Bone strength indices showed significant difference between OVX and OPB treated rats (anti-fracture, anti-twisting, p<0.05). These data suggested that administration of OPB inhibited the loss of bone in OVX rats. CTx level were lower than in the OPB-treated animals compared with OVX. However there was no significant difference between OVX and OPB treated OVX rat. Our results suggest that OPB is effective in preventing the development of bone loss induced by ovariectomy in rats.

• Journal of the korean academy of Pediatric Dentistry
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• v.36 no.3
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• pp.433-439
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• 2009

The purpose of this study was to assess the effect on mandibular growth of botulinum toxin type A (BTXA) injection into the unilateral massester muscle of growing rats at three different growing stages. Thirty six male Sprague-Dawley rats were divided into three groups according to the age (group 1: 4 week-old, group 2: 5week-old, group 3: 6week-old). Then each group was randomly divided into 3 subgroups (control group, unilateral injection group, bilateral injection group). Experimental animals were sacrificed after 4 weeks. Then the jaw measurements were evaluated. The results were as follows: 1. In the group 1, mandibular body length, condylar height and coronoid process height of the unilateral group(BTXA side) and the bilateral group were shorter than those of the control group (p<0.05). 2. In the group 2, anterior region height, condylar height, coronoid process height of the unilateral group(BTXA side) and the bilateral group were shorter than those of the control group (p<0.05). 3. In the group 3, mandibular body length, condylar height, coronoid process height of the unilateral group(BTXA side) and the bilateral group were shorter than those of the control group (p<0.05). 4. There was no significant difference in mandibular measurements between the control side and the injection side in the unilateral group in all age groups (p>0.05).

• Herbal Formula Science
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• v.14 no.2
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• pp.33-44
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• 2006

Objective : The objective of this study is to observe the effect of Yukmijiwhangtangkamibang(YukmD with Liriopis Tuber, Amomi Fructus, Citri Pericarpium, Zizyphi Spinosae Semen, Drynariae Rhizoma Ephedrae Herba, Ginseng Radix, Phellodendri Cortex, on the experimental diabetes. Methods : In order to induce diabetes experimentally, injected streptozoticin to the vein in the tail of rats and then treated oral administration of Yukmi water extracts. In the measurement of the variation levels of glucose, ALP, creatinine, and BUN concentration for each concentration levels for serum (382.5mg/l00g, 510.0mg/100g, 637.5mg/100g), concentration level of glucose significantly decreased in 510.0mg/l00g concentration level of Yukmi. With this 510.0mg/100g concentration level of Yukmijiwhangtanggamibang, the following conclusion was derived from the measurement of the serum levels of glucose, ALP, GOT, GPT, creatinine, and BUN concentration for the streptozotocin injection date of each 4th, 11th, and 18th day. Results : 1. In the measurement for each concentrations. the glucose concentration level in the serum significantly decreased on the 9th day in the Yukmi group. 2. In the measurement for each concentrations, the creatinine concentration level in the serum significantly decreased on the 9th day in the Yukmi group. 3. In the measurement for each dosage dates, the glucose concentration level in the serum significantly decreased on the 18th day in the Yukmi group to which 510.0mg/l00g administrated. 4. In the measurement for each dosage dates, the got concentration level in the serum significantly decreased on the 18th day in the Yukmi group to which 510.0mg/100g administrated. 5. In the measurement for each dosage dates, the creatinine concentration level in the serum significantly decreased on the 18th day in the Yukmi group to which 510.0mg/l00g administrated. Conclusion : Yukmi that is Yukmijiwhangtang with Liriopis Tuber, Amoni Fructus, Citri Pericarpium, Zizyphi Spinosae Semen, Drynariae Rhizoma, Ephedrae Herba, Ginseng Radix and Phellodendri Cortex, is known to have effects to lessen the damages on renal function and liver function without causing damages on liver and kidney.

• Clinical and Experimental Pediatrics
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• v.52 no.1
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• pp.105-110
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• 2009

Purpose : Perinatal asphyxia is an important cause of neonatal mortality and subsequent lifelong neurodevelopmental handicaps. Although many treatment strategies have been tested, there is currently no clinically effective treatment to prevent or reduce the harmful effects of hypoxia and ischemia in humans. Erythropoietin (Epo) has been shown to exert neuroprotective effects in various brain injury models although the exact mechanisms through which Epo functions are not completely understood. This study investigates the effect of Epo on hypoxic-ischemic (HI) brain injury and the possibility that its neuroprotective actions may be associated with iron-mediated metabolism. Methods : HI brain injury was produced in 7-day-old rats by unilateral carotid artery ligation followed by hypoxia with 8% oxygen for 2 h. At the end of HI brain injury, the rats received an intraperitoneal injection of 5,000 units/kg erythropoietin. Random premedication with iron, deferoxamine, iron-deferoxamine, or saline were performed 23 d before HI brain injury. The severity of the brain injury was assessed at 7 d after HI. Results : Single Epo treatment post-HI brain injury reduced the gross and histopathological findings of brain injury. Iron premedication did not increase the incidence or severity of the injury as measured by the damage score. Deferoxamine administration before HI brain injury improved the brain injury as compared to no treatment or Epo treatment. Conclusion : These findings indicate that Epo provides neuroprotective benefits after HI in the developing brain. These findings suggest that Epos neuroprotective actions may involve reducing iron in tissues that mediate the formation of free radicals.

• Clinical and Experimental Pediatrics
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• v.53 no.10
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• pp.898-908
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• 2010

Purpose: The neuroprotective effects of erythropoietin (EPO) have been recently shown in many animal models of brain injury, including hypoxic-ischemic (HI) encephalopathy, trauma, and excitotoxicity; however, limited data are available for such effects during the neonatal periods. Therefore, we investigated whether recombinant human EPO (rHuEPO) can protect against perinatal HI brain injury via an antiapoptotic mechanism. Methods: The left carotid artery was ligated in 7-day-old Sprague-Dawley (SD) rat pups ($in$ $vivo$ model). The animals were divided into 6 groups: normoxia control (NC), normoxia sham-operated (NS), hypoxia only (H), hypoxia+vehicle (HV), hypoxia+rHuEPO before a hypoxic insult (HE-B), and hypoxia+rHuEPO after a hypoxic insult (HE-A). Embryonic cortical neuronal cell culture of SD rats at 18 days gestation ($in$ $vitro$ model) was performed. The cultured cells were divided into 5 groups: normoxia (N), hypoxia (H), and 1, 10, and 100 IU/mL rHuEPO-treated groups. Results: In the $in$ $vivo$ model, Bcl-2 expressions in the H and HV groups were lower than those in the NC and NS groups, whereas those in the HE-A and HE-B groups were greater than those of the H and HV groups. The expressions of Bax and caspase-3 and the ratio of Bax/Bcl-2 were in contrast to those of Bcl-2. In the $in$ $vitro$ model, the patterns of Bcl-2, Bax, and caspase-3 expression and Bax/Bcl-2 ratio were similar to the results obtained in the in vivo model. Conclusion: rHuEPO exerts neuroprotective effect against perinatal HI brain injury via an antiapoptotic mechanism.

• Journal of Oriental Neuropsychiatry
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• v.8 no.1
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• pp.49-68
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• 1997

This study aimed to evaluate the anti-stress effect of Yangsimtang and Yangsimtang+Siyup on the rats in immobilization stress.The experimental animals were immobilized in the stress box(5${\times}$5${\times}$20cm) for 12 hours in a day suring 3 days, and administered 1ｇ/100ｇ of Yangsimtang and Yangsimtang+Siyup and Siyup extract for 12 days before stress. The norepinephrine, epinephrine, dopamine and serotonin contents were measured by HPLC method in various part of rat brain.The following results were observed.1. In frontal cortex the norepinephrine content of control group was 561.${\pm}$24.46 ng/g brain tissue, that of saple 1 group was 430.8$\pm$41.2 ng/g brain tissue, and that of sample 2 group was 417.2$\pm$38.5 ng/g brain tissue. The differences was statistically significant.2. In corpus striatum, the norepinephrine content of control group was 561.3$\pm$27.3 ng/g brain tissue, and that of sample 1 group was 422.1$\pm$21.2 ng/g brain tissue, the dopamine content of control group was 1205.1$\pm$75.9 ng/g brain tissue, that of sample 2 group was 685.6$\pm$41.5 ng/g brain tissue. The differences was statistically significant.3. In hypothalamus, the norepinephrine content of control group was 1165.1$\pm$162.6 ng/g brain tissue, that of sample 2 group was 947.2$\pm$35.7 ng/g brain tissue. The differences was statistically significant.4. In hippocampus, the norepinephrine content of control group was 931.6$\pm$82.2 ng/g brain tissue, that of sample 1 group was 652.1$\pm$47.5 ng/g brain tissue, and that of sample 2 group was 627.4$\pm$31.2 ng/g brain tissue, the dopamine contrnt of control group was 315.4$\pm$28.4 ng/g brain tissue, that of sample 2 group was 208.5$\pm$23.7 ng/g brain tissue. The differences were statistically significant.Base on the above results, it may be concluded that Yangsimtang and Yangsimtang+Siyup are effective to reduce stress.

• Journal of Physiology & Pathology in Korean Medicine
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• v.23 no.2
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• pp.397-404
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• 2009

For standardization of LMK02 quality, Ginsenoside Rg3 of Red Ginseng and Decursin of Angelica gigas Nakai in the constituents of LMK02 were estimated as indicative components. From LMK02 water extract, has been used in vitro test for its beneficial effects on neuronal survival and neuroprotective functions, particularly in connection with APP-related dementias and Alzheimer's disease (AD). $A{\beta}$ oligomer derived from proteolytic processing of the ${\beta}$-amyloid precursor protein (APP), including the amyloid-${\beta}$ peptide ($A{\beta}$), play a critical role in the pathogenesis of Alzheimer's dementia. We determined that oligomer amyloid-${\beta}$ ($A{\beta}$) have a profound attenuation in the increase in rat hippocampus H19-7 cells from. Experimental evidence indicates that LMK02 protects against neuronal damage from cells, but its cellular and molecular mechanisms remain unknown. Using a hippocampus cell line on $A{\beta}$ oligomer-induced neuronal cytotoxicity, we demonstrated that LMK02 inhibits formation of $A{\beta}$ oligomer, which are the behavior, and possibly causative, feature of AD. In the Red Ginseng, the average amounts of Ginsenoside Rg3 were $47.04{\mu}g/g$ and $42.3{\mu}g/g$, 90 % of its weight were set as a standard value. And, in the Angelica gigas Nakai, the average amounts of Decursin were 2.71 mg/g and 2.44mg/g, 90 % of its weight were also set as a standard value. The attenuated $A{\beta}$ oligomer in the presence of LMK02 was observed in the conditioned medium of this $A{\beta}$ oligomer-induced cells under in vitro. In the cells, LMK02 significantly activated antiapoptosis and decreased the production of ROS. These results suggest that neuronal damage in AD might be due to two factors: a direct $A{\beta}$ oligomer toxicity and multiple cellular and molecular neuroprotective mechanisms, including attenuation of apoptosis and direct inhibition of $A{\beta}$ oligomer, underlie the neuroprotective effects of LMK02 treatment.

• YAKHAK HOEJI
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• v.44 no.3
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• pp.224-231
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• 2000

$Nokyangbotang^{TM}$ (NYBT) is a kind of powerful food for health and have been drunk at a oral dose of 80 ml (99.5 mg) three times per day: It has not been well studied about the anti-fatigue and hepatoprotective activity. In this experiments, we evaluated pathophysiologically the effect of NYBT on swimming time in mouse and hepatoprotective activity in rats intoxicated with carbon-tetrachloride. NYBT was nontoxic in orally acute toxicity test ($LD_{50}$, 320 ml/60 kg): a nontoxic food in more four times of one-shoot dosage (80 ml) to human. Weight-loaded forced swimming test was carried out to measure the swimming time of mice with a 4% load of body weight in plastic cylinder (diameter $10{\;}cm{\;}{\times}{\;}height{\;}20{\;}cm$) on water bath at $25^{\circ}C$, and the anti-fatigue activity represented the ratio of swimming time of experimental group to that of control group. NYBT had dose-dependent anti-fatigue activity Mice administered NYBT at a dose of 320 ml/60 kg once daily for 5 days could swim about two times more than control. Hepatoprotective activities of NYBT were examined by the determination of malonedialdehyde (MDA) and pathological survey in liver and liver function test of rat intoxicated with $CCl_4$ at i.m. dose of 2 ml/kg once daily for 7days. NYBT decreased dose-dependently thiobarbituric acid reactive substance: Oral administration of NYBT at a dose of 20 ml/60 kg was $38.51{\;}{\pm}{\;}3.02$ nmol MDA/g of tissue, that of 80 ml/60 kg was $33.76{\;}{\pm}{\;} 1.84$ nmol MDA/g of tissue, and that of 320 ml/60 kg was $32.87{\;}{\pm}{\;}1.90$ nmol MDA/g of tissue as compared with control group ($43.61{\;}{\pm}{\;}2.85$ nmol MDA/g of tissue). All rats administered NYBT at a dose of 320 ml/60 kg were survival as compared with 40% survival of control animals, and GPT activity of rats administered NYBT at a dose of 80 ml/60 kg was decreased as compared with control. In histopathological survey, NYBT improved slightly the fatty changes of hepatocytes around centrilobular area. These results suggest that NYBT has anti-fatigue and hepatoprotective activity in rats and mice.

• Applied Microscopy
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• v.25 no.3
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• pp.51-62
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• 1995

It has been well known that ischemia and reperfusion injury to skeletal muscle following an acute arterial occlusion causes significant morbidity and mortality. The skeletal muscle, which contains high energy phosphate compounds, has ischemic tolerance. During the ischemia, the ATP is catalyzed to hypoxanthine anaerobically and hypoxanthine dehydrogenase is converted to xanthine oxidase. During reperfusion, the hypoxanthine is catalyzed to xanthine by xanthine oxidase under $O_2$, presence and that results in production of cytotoxic oxygen free radicals. These cytotoxic free radicals, $O_2^-,\;H_{2}O_2,\;OH^-$, are toxic and make lesions in skeletal muscle during reperfusion. The authors perform the present study to investigate the effects of allopurinol, the inhibitor of xanthine oxidase, on reperfused ischemic skeletal muscles by observing the ultrastructural changes of the muscle fibers. A total of 48 healthy Sprague-Dawley rats weighing from 200 g to 250 g were used as experimental animals. Under urethane(3.0mg/kg., IP) anesthesia, lower abdominal incision was done and the left common iliac artery were ligated by using vascular clamp for 1, 2 and 6 hours. The left rectus femoris muscles were obtained at 6 hours after the removal of vascular clamp. In the allopurinol pretreated group, 50mg/kg of allopurinol was administered once a day for 2 days and before 2 hours of ischemia. The specimens were sliced into $1mm^3$ and prepared by routine methods for electron microscopic observations. All preparations were stained with uranyl acetate and lead citrate, and then observed with Hitachi -600 transmission electron microscope. The results were as follows: 1. In 1 hour ischemia/6 hours reperfused rectus femoris muscles of rats, decreased glycogen particles and electron density of mitochondrial matrix and dilated terminal cisternae are seen. In 2 hours ischemia/6 hours repersed rectus femoris muscles of rats, mitochondria with electron lucent matrix, irregularly dilated triad and spheromembranous bodies are observed. In 6 hours ischemia/6 hours reperfused rectus femoris muscles of rats, irregularly arranged myofibrils, and many spheromembranous bodies, fat droplets and lysosome are seen. 2. In 1 hour ischemia/6 hours reperfused rectus femoris muscles of rats pretreated with allopurinol, decreased glycogen particle and dilated cisternae of sarcoplasmic reticulum and triad are observed. In 2 hours ischemia/6 hours reperfused rectus femoris muscles of rats pretreated with allopurinol decreased electron density of mitochondrial matrix and spheromembranous bodies are seen. In 6 hours ischemia/6 hours reperfused rectus femoris muscles of rats pretreated with allopurinol, mitochondria with electron lucent matrix, spheromembranous bodies and dilated cisternae of sarcoplasmic reticulum and terminal cistern are observed. The results suggest that the allopurinol attenuates the damages of the skeletal muscles of rats during ischemia and reperfusion.