• The Korean Journal of Physiology and Pharmacology
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• 제9권5호
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• pp.275-282
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• 2005

By using differential display, we identified one of the genes encoding the multi-subunit complex protein V-ATPase, c subunit gene (ATP6L), and showed alterations of the gene expression by oxidative stresses. Expression of the ATP6L gene in Neuro-2A cells was increased by the treatment with $H_2O_2$ and incubation in hypoxic chamber, implying that the expression of the ATP6L gene is regulated by oxidative stresses. To examine mechanisms involved in the regulation of the gene expression by oxidative stresses, the transcriptional activity of the rat ATP6L promoter was studied. Transcription initiation site was determined by primer extension analysis and DNA sequencing, and promoter of the rat ATP6L and its deletion clones were constructed in reporter assay vector. Significant changes of the promoter activities in Neuro-2A cells were observed in two regions within the proximal 1 kbp promoter, and one containing a suppressor was in -195 to -220, which contains GC box that is activated by binding of Sp1 protein. The suppression of promoter activity was lost in mutants of the GC box. We confirmed by electrophoretic mobility shift and supershift assays that Sp1 protein specifically binds to the GC box. The promoter activity was not changed by the $H_2O_2$ treatment and incubation in hypoxic chamber, however, $H_2O_2$ increased the stability of ATP6L mRNA. These data suggest that the expression of the ATP6L gene by oxidative stresses is regulated at posttranscriptional level, whereas the GC box is important in basal activities of the promoter.

• The Journal of Korean Physical Therapy
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• 제22권3호
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• pp.79-85
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• 2010

Purpose: Many trials for new therapeutic approaches such as stem cell-based transplantation have been conducted to improve the repair and regeneration of injured cord tissue and to restore functions following spinal cord injury (SCI) in animals and humans. Adipose tissue-derived stromal cells (ATSCs) have multi-lineage potential to differentiate into cells with neuron-like morphology. Most studies of stem cell transplantation therapy after SCI are focused on cellular regeneration and restoration of motor function, but not on unwanted effects after transplantation such as neuropathic pain. This study was focused on whether transplantation of ATSCs could facilitate or attenuate hindpaw pain responses to heat, cold and mechanical stimulation, as well as on improvement of locomotor function in a rat with SCI. Methods: A spinal cord injury rat model was produced using an NYU impactor by dropping a 10 g rod from a height of 25 mm on to the T9 segment. Human ATSCs (hATSCs; approximately $5{\times}10^5$ cells) or DMEM were injected into the perilesional area 9 days after the SCI. After transplantation, hindpaw withdrawal responses to heat, cold and mechanical allodynia were measured over 7 weeks. Motor recovery on the Basso, Beattie, and Bresnahan (BBB) locomotor rating scale and on the inclined plane test were also evaluated. Results: The present study demonstrated that increased hindpaw withdrawal responses to cold allodynia was observed in both groups after transplantation, but the development of cold-induced allodynia in the hATSC transplantation group was significantly larger than in the control group. The difference between the two groups in locomotor functional improvement after SCI was also significant. Conclusion: Careful consideration not only of optimal functional benefits but also of unintended side effects such as neuropathic pain is necessary before stem cell transplantation therapy after SCI.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• 제2권1호
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• pp.59-64
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• 1999

목 적: 저자들은 백서에서 수술적으로 담도 결찰전과 결찰 4주 후에 지용성 비타민(vitamin A와 D)의 혈중 농도 변화 및 담도 결찰 후 담즙산을 투여했을 때 장관내 지용성 비타민의 흡수 변화에 대하여 알아보고자 하였다. 대상 및 방법: 생후 4주된 Sprague-Dawley rats을 대상으로 하여 수술적으로 담도를 결찰하였다. 담도 결찰 전과 결찰 4주후의 혈중 ALT, total bilirubin, vitamin A, vitamin D의 농도를 측정하였다. 백서들은 담도 결찰 후 4주간 사육하였으며, 사육기간 중 비타민만을 투요한 군, 담즙산을 투여한 군 및 UDCA를 투여한 3군으로 나누었다. 결 과: 1) 수술전 혈중 농도(평균): ALT 74.2 IU, total bilirubin 0.26 mg/dL; vitamin D 13.01 ng/mL vitamin A $0.87\;{\mu}g/mL$, total bile acids $25.16\;{\mu}mol/L$. 2) 수술 4주후 농도(평균): ALT 100.7 IU, total bilirubin 2.58 mg/dL; vitamin D 7.89 ng/mL vitamin A $1.37\;{\mu}g/mL$, total bile acids $278.22\;{\mu}mol/L$. 3) 수술후 각 군간의 혈중 vitamin A와 vitamin D의 농도 차이는 없었다. 결 론: 담도 결찰 후 vitmain A 혈중 농도는 상승 하였으며, vitamin D 농도는 감소하였다. 경구로 담즙산을 투였을 때 혈중 지용성 vitamin 농도는 투여하지 않은 경우와 차이가 없었다.

• 한국식품과학회지
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• 제46권2호
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• pp.249-255
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• 2014

본 연구에서는 사용된 가시오가피 영지버섯 발효물과 가시오가피 상황버섯 발효물에 대한 열수추출물을 최고 2 g/kg의 농도로 단회 투여한 SD-rats에 체중 변화, 임상증상 등에서 어떠한 독성도 관찰할 수 없었으며, 1 g/kg 이하의 농도로 4주간 반복 투여한 SD-rats에서도 체중변화, 임상증상, 장기 무게, 혈액학적 성상, 혈액생화학적 성상 등에서 어떠한 독성과 비정상적인 소견을 관찰할 수 없었다. 따라서, 본 연구의 결과로 볼 때 가시오가피 영지버섯 발효물 열수추출물(FM-5111)과 가시오가피 상황버섯 발효물 열수추출물(FM-5131)은 본 연구에서 사용한 농도 내에서의 안전성을 확인할 수 있었다. 황 함유 아미노산의 결핍은 여러 가지 간질환 등의 증상을 야기한다(27). 또한, Choi와 Ahn(28)은 오가피 부위별 50% (v/v) 메탄올 추출액의 전자공여능은 줄기 추출물에서 90.21%, 뿌리 추출물에서 85.71%로 높은 활성을 보고하여 오가피의 항산화능을 규명하였다. 따라서, 본 연구에 사용된 시료 또한 항산화능과 같은 기능성을 가질것으로 사료되며, 추가 연구로 아미노산 분석을 통해 황 함유 아미노산의 함량 변화를 분석하고 간 기능 개선 효능을 평가하여 안전성이 확보된 기능성 식품소재 개발 연구를 진행할 계획이다.

• The Korean Journal of Physiology and Pharmacology
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• 제18권5호
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• pp.377-381
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• 2014

Propofol is a widely used anesthetic. Many studies have shown that propofol has direct effects on blood vessels, but the precise mechanism is not fully understood. Secondary intrapulmonary artery rings from male rats were prepared and mounted in a Multi Myograph System. The following constrictors were used to induce contractions in isolated artery rings: high $K^+$ solution (60 mmol/L); U46619 solution (100 nmol/L); 5-hydroxytryptamine (5-HT; $3{\mu}mol/L$); or phenylephrine (Phe; $1{\mu}mol/L$). The relaxation effects of propofol were tested on high $K^+$ or U46619 precontracted rings. Propofol also was added to induce relaxation of rings preconstricted by U46619 after pretreatment with the nitric oxide synthase inhibitor $N^G$-nitro-L-arginine methyl ester (L-NAME). The effects of propofol on $Ca^{2+}$ influx via the L-type $Ca^{2+}$ channels were evaluated by examining contraction-dependent responses to $CaCl_2$ in the absence or presence of propofol (10 to $300{\mu}mol/L$). High $K^+$ solution and U46619 induced remarkable contractions of the rings, whereas contractions induced by 5-HT and Phe were weak. Propofol induced dose-dependent relaxation of artery rings precontracted by the high $K^+$ solution. Propofol also induced relaxation of rings precontracted by U46619 in an endothelium-independent way. Propofol at different concentrations significantly inhibited the $Ca^{2+}$-induced contractions of pulmonary rings exposed to high $K^+$-containing and $Ca^{2+}$-free solution in a dose-dependent manner. Propofol relaxed vessels precontracted by the high $K^+$ solution and U46619 in an endothelium-independent way. The mechanism for this effect may involve inhibition of calcium influx through voltage-operated calcium channels (VOCCs) and receptor-operated calcium channels (ROCCs).

• 동의생리병리학회지
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• 제29권4호
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• pp.305-312
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• 2015

Paeonol is a major component found in the Paeoniaceae family such as Paeonia suffruticosa Andrews. Paeonia suffruticosa Andrews has traditionally been used to enhance blood flow and relieve joint pain in east Asian countries including China, Korea and Japan. Current research has shown that paeonol blocked the voltage-gated sodium channel and L-type calcium channel. However, there is a lack of research to reveal the relation between cardiac function and blockade of ion channels by paeonol. Therefore, the aim of this study is to investigate whether paeonol has anti-arrhythmic effects via modulating cardiac ion channels. It is collected that the effects of paeonol on multiple ion channels such as the fast sodium channel and L-type calcium channel from published papers. To incorporate the information on multi-channel block, we computed the effects using the mathematical cardiac model of the guinea-pig and rat ventricular cells (Noble 1998 and 1991 model) and induced early after-depolarizations (EADs) to generate an arrhythmia in the whole heart. Paeonol slightly shortened the action potential duration in the normal cardiac ventricular action potential by the inhibition of sodium channel and L-type calcium channel. Paeonol presented the protective effect from EADs by the inactivation of sodium channel but not L-type calcium channel. Paeonol did not show any changes when it treated on normal ventricular cells through the inhibition of sodium channel, but the protective effect of paeonol through sodium channel on EADs was dose-dependent. These findings suggest that paeonol and its original plant may possess anti-arrhythmic activity, which implies their cardioprotective effects.

• 대한의생명과학회지
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• 제16권4호
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• pp.213-220
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• 2010

Although an adequete intake of calcium (Ca) is recommended for the treatment and prevention of osteoporosis, the intake of Ca should be restricted because of its low rate of intestinal absorption. The purpose of this experiment was to identity the effect of the combined administration of Aquamin F (AQF) (a calcium agent) and lactic acid bacteria (LAB) on osteoporosis. Thirty ovariectomized (OVX) rats and six control rats were assigned to the following six groups, with six animals per group: sham Ca-deficient diet (Ca-D), OVX, LAB, AQF, and LAB-AQF. During the experiment, the body weight was measured; and after the experiment was completed, the serum biochemical analysis, the alkaline phosphatase, calcium, and inorganic phosphorus leves were measured. The tissue of the femur was stained and then scanned via CT. The body weight of the OVX group increased more significantly than that of the control group. The results of the bone mineral content (BMC), Bone mineral density (BMD), serum biochemical analysis and histological test on the femur epiphysis showed no difference between the OVX group and the LAB group, whereas the results of the AQF group were more significant than those of the OVX group. In particular, the LAB+AQF group showed more significant increases in the aforementioned results than the AQF group. This experiment showed that the combined administration of AQF and LAB in ovariectomized rats more significantly increased bone density than did a single administration of either AQF or LAB.

• Natural Product Sciences
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• 제20권4호
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• pp.251-257
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• 2014

Chungsimyeonja-tang (CSYJT) is an herbal decoction that consists with 12 herbal medicines. CSYJT has been shown to have anti-stress, anti-allergic and anti-oxidant effects. The aim of this study was to determine flavonoid contents in CSYJT and evaluate its protective effect against cisplatin induced nephrotoxicity using both in vitro (porcine renal epithelial cell; PK15 cell) and in vivo (Sprague Dawley rat) experiments. In the present study, thee mean contents of baicalin, wogonoside and baicalein in CSYJT were 14.65, 5.27 and 0.02 mg/g, respectively. The CSYJT extract treatment attenuated the following alteration in porcine renal epithelial (PK15) cell: the increase in reactive oxygen species (ROS), the glutathione depletion and the increase in p53 expression induced by cisplatin treatment. In the in vivo study, rats were orally treated with CSYJT extract once a day for 28 days. Five days before the last treatment, cisplatin (5 mg/kg) was intraperitoneally injected to induce acute renal failure. Increased blood urea nitrogen (BUN) and creatinine (CRE) levels after cisplatin treatment were ameliorated by pretreatment of CSYJT extract. In addition, lipid peroxidation was decreased and antioxidant enzyme (glutathione) was recovered in CSYJT pretreated kidney tissue. In histopathological examination, CSYJT pretreated group showed ameliorated pathological alteration after cisplatin injection with decreased apoptosis. Taken together, pretreatment of CSYJT could ameliorate cisplatin-induced nephrotoxicity.

• 동의생리병리학회지
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• 제25권3호
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• pp.451-458
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• 2011

The medicinal mushroom Inonotus obliquus is a traditional and widely used multi-functional fungus. In this study, we have investigated whether Inonotus obliquus (Chaga mushroom) extracts exerts anti-oxidant effects on cisplatin-induced cytotoxicity in auditory cell line, HEI-OC1 cells. First of all, Chaga extracts has no harmful effects on viability of HEI-OC1 cells in the dose range of $65{\sim}125{\mu}g/m{\ell}$. Moreover, it shows cyto-protective effects on the cells treated with cisplatin-induced cytotoxicity in HEI-OC1 cells and the damage of hair cells arrays of the rat primary organ of Corti explants in the presence of cisplatin. Pretreatment with Chaga extracts inhibited the cell death, reactive oxygen species generation (ROS), lipid peroxidation induced by cisplatin. These effects were associated with the induction of antioxidant enzyme by Chaga extracts. We further investigated the effects of Chaga extracts on expression of antioxidant enzymes such as Cu, Zn superoxide dismutase (SOD 1) and Mn SOD (SOD 2) by RT-PCR. In addition, Chaga extracts shows SOD activity and SOD protein expression in cisplatin treated group induced similar to control group. Taken together, these results indicate that Chaga extracts can prevent cisplatin-induced cytotoxicity by radical-scavenging activity (SOD activity) in HEI-OC1 cells. It might be an effective as antioxidant and further studies on the chemo-preventive mechanisms of Inonotus obliquus are needed.

• 대한예방한의학회지
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• 제9권1호
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• pp.119-133
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• 2005

Traditional herbal medicine is widely used among the Korean people, and other eastern Asian countries employ similar therapies as well. In recent years, due to increasing interest in herbal medicines, many researches have been made on the toxicity and side effects of herbal medications. Through private and public media, there have been many opinions suggesting taking herbal medicines is very harmful, especially on the liver and kidney functions. This assertion has been mainly presented by the doctors that practice western medicine, But this assertion is never based on adequate knowledge of herbal medicine. This study aims to provide the evidences that taking herbal medicines is safe on the renal functions. Four frequently used herbal medications(Sipjeondaebotang, Bojungigitang, Ojeoksan, and Yukmijihwangtang) were used to test the toxicity of herbal medicine oh the lab animal model(SD-Rat). There is no significant difference in body weight and kidney weight after herbal medication for 1 month. In all experimental groups, no abnormal findings were observed in histological study, and lab renal function index(BUN, creatinine, uric acid). These results say that four herbal multi-used-medicines, when medicated, is safe from the renal toxicity in lab animal model.