• Biomolecules & Therapeutics
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• v.10 no.1
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• pp.25-31
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• 2002

This study was carried out to identify the effect of oxidative stress on the pathogenesis of manganese intoxication. Five rats in experimental group were given with $MnCl_2$intraperitoneally for 4 weeks(4 mg/kg once daily 5 days per week) and another five rats for control group were given with normal saline. In experimental group, manganese concentrations increased significantly in nucleus accumbens by 142% (p<0.05), SOD activities increased significantly by 124%(p<0.01), and MDA concentrations increased significantly 148%(p<0.05) compared with control group. Among fatty acids, total n-6 polyunsaturated fatty acids(PU) increased significantly by 231%(p<0.05) compared with control group. Arachidonic acids(AA) increased by 224%(p<0.05), and these increase were composed mostly of n-6 polyunsaturated fatty acids(PUFA). Among n-3 PUFAs except linolenic acids, eicosapentanolc acid(EPA) decreased significantly by 38%(p 0.01) and docosahexanoic acids(DHA) decreased by 30% p<0.05) compared with control group. Our results suggest that the oxygen free radicals produced by manganese may cause compositional changes of fBtty acids in nucleus accumbens of the rat. Characteristics of fatty acids compositional changes by manganese were the decrease of EPAs and DHAs(n-3 PUFAs), and increase of AAs(n-6 PUFAs). These changes with the increase of MDA, suggest that manganese neurotokxcity is caused by lipid perokidation mediated with oxygen free radicals, especially superoxide radicals.

• Korean Journal of Veterinary Research
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• v.44 no.2
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• pp.207-215
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• 2004

It is well known that the hypothalamic-pituitary-adrenocortical (HPA) axis is under the negative feedback control of adrenal corticosteroids. Previous studies have suggested that glucocorticoids can regulate neuroendocrine cells in the paraventricular nucleus (PVN) by modulating catecholaminergic transmission, a major excitatory modulator of the HPA axis at the hypothalamic level. But, the effects of corticosteroids on the expression of adrenoceptor subtypes are not fully understood. In this work, we examined mRNA levels of six adrenoceptor subtypes (${\alpha}_{1A}$, ${\alpha}_{1B}$, ${\alpha}_{2A}$, ${\alpha}_{2B}$, ${\beta}_1$ and ${\beta}_2$) in the PVN of normal and adrenalectomized (ADX) rats. Total RNA ($2.5{\mu}g$) was extracted from PVN micropunches of brain slices ($500{\mu}m$) and analyzed by reverse transcription-polymerase chain reaction (RT-PCR). The levels of corticotropin-releasing hormone (CRH) mRNA were increased in the ADX rats relative to normal rats, indicating that the PVN had been liberated from the negative feedback of corticosteroids. Among the six adrenoceptor subtypes examined, mRNA levels for ${\alpha}_{1B}$- and ${\beta}_1$-adrenoceptors were increased, but the level for ${\beta}_2$-adrenoceptors was decreased in the ADX rats. The mRNA levels for the other three subtypes and for the general and neuronal specific housekeeping genes, glyceroaldehyde-3-phosphate dehydrogenase (GAPDH) and N-enolase, respectively, were not changed in the ADX rats. In conclusion, the results indicate that adrenal steroids selectively regulate the gene expression of adrenoceptor subtypes in the PVN.

• Herbal Formula Science
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• v.13 no.1
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• pp.49-69
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• 2005

This Study was designed to investigate the effect of Sunkihwalhyul -Tang extract(SHT) on the change of cerebral hemodynamics [regional cerebral blood flow(rCBF), pial arterial diameter(PAD) and mean arterial blood pressure(MABP)] in normal and cerebral ischemic rats, and further to determine the mechanisms of action of SHT on hemodynamics. In addition, this study was designed to investigate whether SHT inhibits lactate dehydrog enase(LDH) activity in neuronal cells and cytokines production in serum of cerebral ischemic rats. The results were as follows 1. SHT significantly increased rCBF and PAD in a dose-dependent manner, but MABP was not changed by injecting SHT. These results suggest that SHT significantly increases rCBF by dilating PAD. 2. The SHT-induced increase in rCBF was significantly inhibited by pretreatment with indomethacin(IDN, 1 mg/kg, i.p.), an inhibitor of cyclooxygenase and methylene blue(MTB, $10{\mu}g/kg$, i.p.), an inhibitor of guanylate cyclase. 3. The SHT-induced dilation in PAD was significantly inhibited by pretreatment with IDN and MTB. 4. The SHT-induced some increase in MABP was significantly increased by pretreatment with IDN. These results suggest that the mechanism of action of SBT is mediated by guanylate cyclase. 5. Both rCBF and PAD were significantly and stably increased by SHT(10 mg/kg, i.p.) during the period of cerebral reperfusion, which contrasted with the findings of rapid and marked increase in control group. 6. SBH significantly inhibited LDH activity in neuronal cells. These results suggest that SHT prevents the neuronal death. 7. In cytokine production in the senlm drawn from femoral artery 1 hr after middlecerebral arterial occlusion, sample group showed significantly decreased production of IL-1$\beta$ production, decreased production TNF-$\alpha$ and increased Production of IL-10 compared with control group. 8. In cytokine production in the serum drawn femoral artery 1 hr after reperfusion, sample group showed significantly decreased production of IL-1$\beta$ and TNF-$\alpha$ as wellas significantly increased production of IL10 compared with control group. These results suggest that SHT mediated by guanylate cyclase has inhibitive effect on the brain damage by inhibiting LDH activity, IL-1$\beta$ and TNF-$\alpha$ production, and by accelerating IL-10 production. The present author thinks that SHT has an anti-ischemic effects through the improvement of cerebral hemodynamics and inhibitive enects on the brain damage.

• The Korea Journal of Herbology
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• v.22 no.4
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• pp.253-260
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• 2007

Objectives : Intracerebral hemorrhage (ICH) is characterized by breakdown of blood vessels within the brain parenchyma. Fundamental therapeutic strategies for ICH, particularly those aimed at neuroprotection, have to be established. So in this experiment, the effects of Woowhangchongshim-won, a traditional prescription formula for treating Cerebral Apoplexy in Asian countries, were investigated. Methods : After intraperitoneal injection of chloralhydrate, rats were placed in a stereotaxic frame. ICH was induced by injection of 1 U collagenase type IV and drug was administered orally for 10 days. The molecular profile of cerebral hemorrhage in rat brain tissue was measured using micro array technique to identify up- or down- regulated genes in brain tissue. These genes induced by brain damage were mainly concerned with general metabolic process such as primary metabolic process, cellular metabolic process, macromolecule metabolic process, and biosynthetic process. Results : The number of genes increased in control and not-changed in experiment was 374, and decreased in control and not-changed in experiment was 527. We are concerned with genes that can be recovered by treatment with medicine, it is especially interesting to above types of genes. Conclusions : Upon medicine treatment to the rat having cerebral hemorrhage, expressions of some genes were restored to normal level. Further analysis using protein interaction database identified some key molecules that can be used for elucidation of therapeutical mechanism of medicine in future.

• Journal of Life Science
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• v.19 no.7
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• pp.934-942
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• 2009

This study was performed to observe the effect of hot-water extracts from garlic and 13 kinds of medicinal plants composites (GMP) on hyperlipidemia and hepatoprotective activity in rats administered with alcohol. Male Sprague-Dawly rats were fed an AIN-93 diet (Normal), a normal diet plus ethanol (control, 10 ml of 40% ethanoljkgjday), a control diet plus 0.5% garlic and 1.0% medicinal plants composites extracts (GMP-I), and a control diet plus 1.0% garlic and medicinal plants composites extracts (GMP-II) for 7 days. Blood glucose was higher than the control, but it was markedly decreased in the GMP-II group. Elevation total lipids, cholesterol, triglyceride and phospholipids in serum were markedly decreased in rats fed with GMP-I. GMP-II also inhibited the increase of lipid content in serum. Activities of GOT, GPT, $\gamma$-GTP and ALP in serum elevated by alcohol were significantly inhibited in the GMP group. TBARS content of serum was significantly decreased in GMP groups administered with garlic and medicinal plant extracts. Extracts of garlic and medicinal plants play an important role in recovering liver function in rats from alcohol induced damage.

• The Journal of Korean Medicine
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• v.29 no.3
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• pp.144-154
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• 2008

Objectives: Osteoporosis is one of the most common metabolic bone disorders in the menopausal stage, a disease signified by decrease of bone mass. The purpose of this study was to learn how Lycii Fructus influences SD rats with osteoporosis caused by the removal of the ovaries. Methods: After the removal of the ovaries from 24 female Sprague-Dawley rats, they were divided into a normal group, a control group, and a Lycii Fructus (25mg/100g) administration group. After 8 weeks, the rats were sacrificed and their weights, albumin, AST, ALT, ALP, total-cholesterol, triglyceride, P, Ca, T4, E2, weight of a femur, ash content of the tibia, and area and thickness of trabecular bone were measured. Results: Regarding the density of ALT, ALP, and estradiol from serum, the Lycii Fructus group was significantly decreased compared to the control group, and the density of phosphorous and calcium also decreased slightly. Moreover, albumin, triglyceride, and T4 showed an increasing propensity, but AST and total-cholesterol showed a decreasing propensity, but not significant. Regarding the variation of bone, femur weight and ash content of tibia, the Lycii Fructus group was increased compared to the control group but significance wasn't shown. The Lycii Fructus group increased significantly over the control group in area and thickness of trabecular bone and osteoclast number. Conclusions: From the results of the above study, Lycii Fructus should be effective for osteoporosis treatment and prevention.

• Journal of Physiology & Pathology in Korean Medicine
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• v.18 no.6
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• pp.1714-1721
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• 2004

This experimental study was designed to investigate the mechanism of Palmul-Tang(PMT) on the changes of cerebral hemodynamics in rats. The changes of cerebral hemodynamics in normal rats were as follows ; The PMT-induced increase in regional cerebral blood flow was significantly inhibited by pretreatment with indomethacin(1㎎/㎏, i.p.), an inhibitor of cyclooxygenase, and was inhibited by methylene blue(10㎍/㎏, i.p.), an inhibitor of guanylate cyclase. The PMT-induced dilation in pial arterial diameter was significantly inhibited by pretreatment with indomethacin and methylene blue. The PMT-induced increase in mean arterial blood pressure was significantly inhibited by pretreatment with indomethacin but was increased by methylene blue. This results were suggested that the mechanism of PMT was mediated by cyclooxygenase. The changes of cytokine production in cerebral ischemic rats were as follows ; In cytokine production of serum by drawing from femoral arterial blood after middle cerebral arterial occlusion 1hr, sample group was decreased IL-1β and TNF-α production compared with control group, IL-10 production of sample group was similar to that of control group, but sample group was significantly increased TGF-β production compared with control group. In cytokine production of serum by drawing from femoral arterial blood after reperfusion 1hr, sample group was significantly decreased IL-1β production compared with control group and decreased TNF-α production compared with control group. IL-10 production of sample group was similar to that of control group, but sample group was significantly increased TGF-β production compared with control group. In cytokine production of serum by drawing from femoral arterial blood after reperfusion 4 hrs, sample group was significantly decreased IL-1β production compared with control group, but IL-10 production of sample group was similar to that of control group. sample group was increased TNF-α and TGF-β production compared with control group. These results suggested that PMT had inhibitive effect on the brain damage by inhibiting IL-1β and TNF-α production, but by accelerating TGF-β production. The present author thought that PMT had an anti-ischemic effect through the improvement of cerebral hemodynamics and inhibitive effect on the brain damage.

• Journal of Oriental Neuropsychiatry
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• v.14 no.1
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• pp.27-44
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• 2003

Objective : The aim of this study was to assess protective effects of Whangryonhaedoktang on the chronic mild stress (CMS) animal model of depression. Method : Male Sprague-Dawley rats were used for this study. The subjects were divided into 3 groups (CMS-drug group: Whangryonhaedoktang was administered during CMS procedure, CMS-vehicle: water was administered during CMS procedure, normal control group: without CMS procedure). After 4 weeks of CMS procedure, Morris water maze (MWM) test and open field test were executed and tyrosine hydroxylase (TH) was measured in ventral tegmental area (VTA) and locus coeruleus (LC) of rat brain. Result : 1. CMS procedure induced defects of spatial learning in early period of MWM test. 2. CMS Whangryonhaedoktang group showed shorter escape latency in comparison with CMS control group in MWM test on the first day of the test. 3. CMS Whangryonhaedoktang group and CMS control group showed no significant difference of activities and emotional behaviors in comparison with normal control group in open field test. 4. CMS Whangryonhaedoktang group showed significant inhibition effects of TH expression in VTA and LC areas in comparison with CMS control group. Conclusion : These results suggest that Whangryonhaedoktang may have inhibition effects to early period defects of spatial learning and protective antidepressant effects in CMS model rats.

• Journal of Korean Academy of Nursing
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• v.34 no.1
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• pp.150-159
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• 2004

Purpose: The purpose of this study was to determine the effect of DHEA on hindlimb muscles(soleus, plantaris and gastrocnemius) in a focal brain ischemia model rat. Method: Twenty-seven male Sprague-Dawley rats were randomly divided into three groups: CINS(cerebral ischemia + normal saline), CIDH(cerebral ischemia + DHEA), or SHNS(sham + normal saline). Both the CINS and CIDH groups underwent a transient right middle cerebral artery occlusion operation. In the SHNS group, a sham operation was done. 0.34mmol/kg DHEA was administered daily by an intraperitoneal injection for 7days. Results: The muscle weight, muscle fiber cross-sectional area of the Type I muscle fiber of soleus and Type II muscle fiber of plantaris and gastrocnemius, myofibrillar protein content of gastrocnemius, and muscle strength in the CINS group decreased compared with the SHNS group. The muscle weight, muscle fiber cross-sectional area of the Type II muscle fiber of plantaris and gastrocnemius, myofibrillar protein content of soleus, and muscle strength in the CIDH group increased compared with the CINS group. Conclusion: It was identified that muscle atrophy could be induced during 7 days after a cerebral infarction, and DHEA administration during the early stages of a cerebral infarction might attenuate muscle atrophy.

• Investigative Magnetic Resonance Imaging
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• v.3 no.2
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• pp.167-172
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• 1999

Purpose : To evaluate the detection rate of hyperacute intracerebral hemorrhage in echo planar imaging (EPI) and other MR sequences. materials and Methods : Intracerebral hemorrhage was experimentally induced in ten rats. EPI, fast spin-echo (FSE) T2 weighted images, fluid attenuated inversion recovery (FLAIR), spin-echo (SE) T1 weighted images and gradient echo (GE) T1 weight ed images of rat's brains were obtained 2 hours after onset of intracerebral hemorrhage. EPI and FSE T2 images were additionally obtained 30 min and 1 hour after onset of hemorrhage in 3 and 6 rat, repeatedly, For objective visual assessment, discrimination between the lesion and normal brain parenchyma was evaluated on various MR sequences by three radiologists. For quantitative assessment, contrast-to-noise ratio (CNR) was calculated fro hemorrhage-normal brain parenchyma. Statistical analysis was performed usning the Wilcoxon-Ranks test. Results : EPI, FLAIR, and FSE T2 images showed high signal intensity lesions. The lesion discrimination was easier on EPI than on other sequences, and also EPI showed higher signal intensity for the subjective visual assessment. In quantitative evaluation, CNR of the hemorrhagic lesion versus normal brain parenchyma were higher on EPI and FLAIR images (p<0.01). There was no difference in CNR between EPI and FLAIR (p>0.10). On MR images obtained 30 minutes and 1 hour after the onset of intracerebral hemorrhage, the lesion detection was feasible on both EPI and FSE T2 images showing high signal intensity. Conclusion : EPI showed higher detection rate as compared with other MR sequences and could be useful in early detection and evaluation of intracerebral hemorrhage.