• Journal of the korean academy of Pediatric Dentistry
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• v.41 no.4
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• pp.283-291
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• 2014

Patients with extreme anxiety who are unable to cope with dental treatment under non-pharmacological behavioral management method may require sedation, or other forms pharmacological behavioral management method. The aim of this retrospective study was to investigate the effect of concomitant administration of 0.1 mg/kg intramuscular midazolam with or without sevoflurane insufflation sedation on sedation depth and cardiopulmonary function in pediatric patients. We analysed the records of anesthesia on patients who received dental treatment under deep sedation using sevoflurane insufflation from January 2013 to March 2014. Thirty-six children, aged 3 to 6 years, undergoing dental treatment were sedated using either sevoflurane insufflation alone (Group S, n = 18) or a combination of intramuscular injection of 0.1 mg/kg midazolam plus sevoflurane insufflation (Group SM, n = 18). Upon comparison, the average entropy value of group SM was lower than that of group S, but there were no statistically significant difference between the two groups (p > 0.05). The average heart rate and mean arterial pressure of group SM were higher than those of group S (p < 0.05). Concomitant intramuscular injection of 0.1 mg/kg midazolam with sevoflurane insufflation sedation is not sufficient to enhance the quality of sedation.

• The Korean Journal of Pesticide Science
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• v.6 no.2
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• pp.96-104
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• 2002

This study was carried out to investigate cytotoxicity of paraquat on NIH 3T3 fibroblasts, toxicity of paraquat and compensatory effects of 3-methylcholanthrene (3-MC) on the rat lung. In order to conduct MIT [3-(4,5-Dimethylthiazol-2-yl) -2,5-diphenyl -2H-tetrazolium-bromide] and NR (Neutral red) assay, the $5.0{\times}10^4cell/ml$ of NIH 3T3 fibroblast in each well of 24 multi-dish were cultured. After 24 hours, the cells were treated with solution of paraquat (1, 25, 50 and $100{\mu}M$ respectively). After the NIH 3T3 fibroblast of all groups were cultured in same condition for 48 hours. MIT and NR assay were performed to evaluate the cytotoxicity of cell organelles. $MTT_{50}\;and\;NR_{50}$ of paraquat were $1668.97{\mu}M\;and\;1030.85{\mu}M$, respectively. These $IC_{50}$ of Paraquat were decided as a low cytotoxicity by Borenfreund and Puemer (1984). In order to observe the toxicity and compensatory effects of paraquat on the rat lung, Spraque Dawley male rats were used as experimental animals and were divided into paraquat only treated group and simultaneous application group of paraquat and 3-MC, at 30 min and 1, 3, 6, 12, 24, 48 and 96 hrs interval after each treatment. The animals were sacrificed by decapitation and their or the lungs were immediately removed, immersed in fixatives, and were processed with routine method for light microscopic study. Paraffin sections were stained with H&E and iron hematoxylin of Verhoeff. Under the light microscopy, erythrocytes were full in alveolar capillaries at 3 hrs and congested at 24 hrs after paraquat administration. The great alveolar cells (Type II cell) were increased and mitosis of great alveolar were observed in interalveolar septa. Many lymphocytes, macrophages and polymorphonuclear (PMN) cells were observed in connective tissue surrounding lung tissue and germinal center in lymph follicles of terminal bronchiole. Alveolar macrophages were increased in interalveolar septa and alveoli at 48 hrs. And observed many alveolar macrophages at 96 hrs. In iron hematoxylin stain of Verhoeff, Collagen fiber were increased in respiratory bronchiole, interalveolar septa and alveoli and breath of alveoli, and alveolar pore were broaden. But, in paraquat plus 3-MC treated group, morphological changes were mild in lung tissue. These results indicate that 3-MC has a compensatory effects against toxicity of paraquat by conjugation with oxygen.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1995.04a
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• pp.95-95
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• 1995

뇌신경 변성 / 퇴행과 관련된 중요한 병인론 중의 하나는 변성 과정에서 형성된 유리기(free radical)로 인한 항산화계의 평형 소실로 알려져 있다. Aspalatone (APT)의 예상되는 항산화 효능을 검정하기 위하여 본 실험에서는 Kainic acid (KA) 유발 뇌변성 모델을 적용하였다. KA 모델은 변연계의 간질성 경련과 신경세포 변성에 대하여 재현성 있는 병변 모델을 제공해 주며, 이와 같은 신경세포의 병독 기전에 산소 유리기가 관여함이 강력히 시사되고 있기 때문이다. KA 투여로 인하여 지속적이고도 전형적인 간질성 경련이 관찰되고 1일 이내에 높은 치사율을 보였으나 APT으로 인하여 그 간질성 경련 행위와 비율이 억제되고 KA 유발 치사율도 억제되었다. 최종 KA 투여 3일 후에 얻어진 흰쥐 해마 및 대뇌 피질에서 항산화 효소인 Superoxide dismutase (SOD), Catalase (Cat.), Glutathione peroxidase (GSH-PX) 및 과산화지질의 지표인 Malondialdehyde (MDA)를 검정하였다. 대조군에 비하여 KA는 뇌조직의 SOD-1을 유도하였으나, Cat.와 GSH-PX의 활성은 현저히 유도되지 않았고, 반면에 MDA 치는 현저히 증가하였다. 즉, Cat., GSH-PX와 같은 $H_2O$$_2$중화제가 동반 유도하지 않는 SOD의 유도는 세포내 축적되는 $H_2O$$_2$로 인하여 Fenton/Haber-Weiss 반응을 가속화하여 과산화지질화를 촉진함을 시사한다. APT 병용 투여로 SOD는 현저히 유도되지 않았으나 특히 Cat.가 현저히 유도되어지고 MDA는 억제되었다. 이와 같은 생화학적인 결과는 다음의 형태학적인 소견과 일치한다. Fos 관련 항원 (FRA)와 SOD-1을 면역세포화학 (Immunocytochemistry)적 방법으로 이중 표식 (double-labelling) 하였다. FRA는 KA로 인한 신경세포의 자극에 대한 지표로 응용하였고, SOD-1은 퇴행성 뇌질환에서 산화적 손상의 지표로 사용하였다. KA 투여로 해마의 dentate gyrus (DG) 내에 강한 면역환성 (immunoreactivity)이 나타났고 pyramidal cell layer (PCL)와 glia에 SOD-1이 강하게 염색되었다. APT 병용 투여로 상당수의 경련이 일어나지 않은 흰쥐는 해마의 DG에 FRA가 경미하게 염색되었고, PCL에 SOD-1도 경미하게 나타났으나, 경련이 나타난 쥐에서는 KA만을 투여한 흰쥐와 구별되지 않았다. 이상의 APT의 항산화 효과는 KA로 인한 뇌세포 변성 개선에 중요한 인자로 작용할 것으로 사료되나, 보다 명확한 APT의 기전을 검색하고 직접 임상에 응응하기 위하여는 보다 다양한 실험 조건이 보완되어야 찰 것으로 생각된다.

• Journal of Radiation Protection and Research
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• v.17 no.1
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• pp.11-19
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• 1992

To find out an effective way of treating the toxicity of cadmium, concentrations of $K^+,\;Ca^{2+}$ and c-AMP, and activities of GOT and GPT in blood of rats were determined at definite time intervals after administration of cadmium to rats. Cadmium caused more decrease of $Ca^{2+}$ concentration than $K^+$ concentration but increases of GOT and GPT activities and of c-AMP concentrations. The decreased concentration of $Ca^{2+}$ was not recovered by selenium or metallothionein. However, the increased activities of GOT and GPT, and the c-AMP concentration were down regulated remarkably by selenium but not by metallothionein. These results suggested that selenium might have the compensate effects concerning toxic index against cadmium such as increases of GOT and GPT activities, and of c-AMP concentration.

• Tuberculosis and Respiratory Diseases
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• v.43 no.3
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• pp.308-322
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• 1996

Background : Neutrophils are considered to play critical roles in the development of acute respiratory distress syndrome. Histamine, which is distributed abundantly in lung tissue, increases the rolling of neutrophills via increase of P-selectin expression on the surface of endothelial cells and is known to have some interrelationships with IL-1, IL-8 and TNF-$\alpha$. We studied to investigate the effect of the histamine on the acute lung injury of the rats induced by intratracheal insufflation of TNF-$\alpha$ which has less potency to cause lung injury compared to IL-1 in rats. Methods : We intratracheally instilled saline or TNF(R&D, 500ng), IL-1(R&D, 50ng)or histamine of varius dose(1.1, 11 and $55\;{\mu}g/kg$) with and without TNF separately in Sprague-Dawley rats weighing 270-370 grams. We also intratracheally treated IL-1(50ng) along with histamine($55\;{\mu}g/kg$). In cases, there were synergistic effects induced by histamine on the parameters of TNF-induced acute lung injury, antihistamines(Sigma, mepyramine as a $H_1$ receptor blockade and ranitidine as a $H_2$ receptor blockade, 10 mg/kg in each)were co-administered intravenously to the rats treated TNF along with histamine($1.1\;{\mu}g/kg$) intratraeheally. Then after 5 h we measured lung lavage neutrophil numbers, lavage cytokine-induced neutrophil chemoattractants(CINC), lung myeloperoxidase activity(MPO) and lung leak. We also intratracheally insufflated TNF with/without histamine($11\;{\mu}g/kg$), then after 24 h measured lung leak in rats. Statistical analyses were done by Kruskal-Wallis nonparametric ANOVA test with Dunn's multiple comparison test or by Mann-Whitney U test. Results : We found that rats given TNF, histamine alone(11 and $55\;{\mu}g/kg$), and TNF with histamine(l.1, 11, and $55\;{\mu}g/kg$) intratracheally had increased (p<0.05) lung MPO activity compared with saline-treated control rats. TNF with histamine $11\;{\mu}g/kg$ had increased MPO activity (P=0.0251) compared with TNF-treated rats. TNF and TNF with histamine(1.1, 11, and $55\;{\mu}g/kg$) intratracheally had all increased (p<0.05) lung leak, lavage neutophil numbers and lavage CINC activities compared with saline. TNF with histamine $1.1\;{\mu}g/kg$ had increased (p=0.0367) lavage neutrophil numbers compared with TNF treated rats. But there were no additive effect of histamine with TNF compared with TNF alone in acute lung leak on 5 h and 24 h in rats. Treatment of rats with the $H_1$ and $H_2$ antagonists resulted in inhibitions of lavage neutrophil accumulations and lavage CINC activity elevations elicited by co-treated histamine in TNF-induced acute lung injury intratracheally in rats. We also found that rats given IL-1 along with histamine intratracheally did not have increase in lung leak compared with IL-1 treated rats. Conclusion : Histamine administered intratracheally did not have synergistic effects on TNF-induced acute lung leak inspite of additive effects on increase in MPO activity and lavage neutrophil numbers in rats. These observations suggest that instilling histamine intratracheally would not play synergistic roles in neutrophil-mediated acute lung injury in rats.

• Journal of Veterinary Clinics
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• v.30 no.6
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• pp.415-420
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• 2013

This study was performed to examine the anesthetic and cardiopulmonary effects of medetomidine, midazolam and ketamine (MMK) combination in ten beagle dogs. Dogs were randomly allocated to two groups. Treatment group MMK-L received 0.015 mg/kg medetomidine followed by 0.3 mg/kg midazolam and 5 mg/kg ketamine by intramuscular injection. Treatment group MMK-H received 0.02 mg/kg medetomidine followed by 0.3 mg/kg midazolam and 5 mg/kg ketamine by intramuscular injection. Induction, anesthesia, sternal recumbency, standing, walking time, heart rate, arterial blood pressure, rectal temperature, respiratory rate and arterial blood gases were measured. Mean anesthesia time was significantly different between MMK-L group ($52.4{\pm}11.08$ minutes) and MMK-H group ($78.2{\pm}20.72$ minutes). Sedative scores and noxious stimuli were raised to the maximum value at 5 minutes after administration of the test dose and maintained until 40 minutes in both groups. In both groups, the heart rate significantly decreased after MMK administration. The blood pressures (MAP, SAP and DAP) increased after MMK administration but there were no significant differences in blood pressures between two groups. In conclusion, intramuscular administration of medetomidine followed by intramuscular injection of midazolam and ketamine in beagle dogs, leads immediate and sufficient anesthesia and proper doses of medetomidine for minimal adverse effects in intramuscular MMK combination will be 0.015 mg/kg in dogs.

• Journal of Veterinary Clinics
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• v.27 no.2
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• pp.136-141
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• 2010

The aim of this study is to investigate whether medetomidine (MED) and tiletamine/zolazepam (ZT) combination in dogs provide the sufficient analgesia during the period of the stage of surgical anesthesia determined by the response to the noxious stimuli, which were evaluated by the change of electroencephalogram (EEG) and hemodynamic values. Seven clinically healthy, adult beagle dogs were used. They were used repeatedly at interval of a week, according to a randomized design. This study had 2 experimental groups. In Group 1, dogs received $30\;{\mu}g/kg$ of medetomidine and 10 mg/kg of tiletamine/zolazepam. Both drugs were administered intramuscularly. In Group 2, dogs were medicated with the same method as in Group 1, except the pedal withdrawal reflex test was done. In Group 2, interdigital regions were grasped with a mosquito forceps for 30 seconds, every 5 min from 10 min to 45 min after ZT injection. During all recording stages, the power for each band, mean arterial pressure and heart rates were calculated. On EEG, no significant changes were observed between groups. Although mean arterial pressure and heart rate were increased 10 min after ZT injection, no significant differences were observed between groups. In conclusion, the MED and ZT anesthesia in dogs are seemed to provide a satisfactory analgesic effect during the period of surgical anesthesia based on EEG with pedal withdrawal reflex test.

• Korean Journal of Food Science and Technology
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• v.35 no.4
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• pp.713-719
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• 2003

The effects of butanol (BuOH) fraction of Alisma canaliculatum (Ac) with vitamin E in streptozotocin (STZ)-induced diabetic rats were determined. Sprague-Dawley rats were divided into 5 groups: normal, STZ-control, and 3 diabetic-experimental groups. Diabetes mellitus was induced by injection of STZ (45 mg/kg) into the tail vein. The BuOH fraction of Ac and vitamin E were administrated orally in experimental rats for 21 days: Ac group (400 mg/kg), Ac-VE group (Ac 400 mg/kg & vitamin E 10 mg/kg), and VE group (vitamin E 10 mg/kg). The body weight losses were seen in all groups except normal, and the decrements in experimental groups were less than that in diabetic-control group. The plasma glucose levels were significantly lower in Ac group compared to STZ-control group on 21 day (p<0.05). The plasma level of insulin was slightly higher in AC-VE group than other diabetic groups. The plasma cholesterol levels of diabetic-experimental groups were significantly lower than those of STZ-control group on 14 day (p<0.05). ALT and AST activities of diabetic-experimental groups were significantly lower than that of STZ-control group (p<0.05). The results suggested that the BuOH fraction of Ac might possess hypoglycemic properties in STZ-induced diabetic rats and no synergistic effect of vitamin E was seen during the experimental period.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1994.04a
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• pp.343-343
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• 1994

1. 목 적 : 혈액 중에 존재하는 약물은 대부분 혈장 단백질과 결합하며, 비단백 결합성 약물만이 생체막을 통과하여 여러 조직에 분포되고, target eel1에서 약리학적 작용을 나타내며, 대사, 배설 될 수 있다. 단백결합율이 높은 약물일수록 비결합성 약물의 양은 적어지며, 따라서 비결합성 약물의 증가는 약효의 상승을 의미하게 된다. 최근 만성 질환에 한약의 병용투여가 증가하고 있다. 본 실험에서는 단백결합율이 높은 감초의 주성분인 Glycyrrhizic acid(GA)와 고혈압 치료제로 많이 사용되는 칼슘 길항제를 병용 투여할 경우, 칼슘 길항제의 혈장 단백결합에 미치는 영향을 살펴 보았다. 2. 방 법 : Diltiazem hydrochloride, Verapamil hydrochloride, Nifedipine 와 GA를 model 약물로 하여 평형 투석법과 한외 여과법을 이용하여 fatty acid free human serum albumin(HSA), Low density lipoprotein( LDL ), of-Acid glycoprotein(AAG), plasma 각각에 대한 결합율을 HPLC로 분석하였으며 또한 Scatchard plot를 이용하여 binding parameter를 구하였다. 3. 결과 및 고찰 : GA는 Diltiazem의 HSA와 plasma의 결합율에 영향을 미쳤으며, Verapamil의 HSA, LDL, AAG, Plasma 결합율에, 그리고 Nifedipine의 HSA, LDL, Plasma의 단백 결합율에 영향을 주었으며, 각각 n과 Ka값에 변화를 주었다.

• Journal of the Korean Society of Food Science and Nutrition
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• v.29 no.3
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• pp.479-484
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• 2000

흰쥐에 에탄올을 투여해 간 손상을 유도한 후 굼벵이를 투여해 굼벵이가 혈청과 간의 지진대사에 어떠한 영향을 미치는가를 조사하였다. 혈청지질 중 에탄올에 의해 증가된 triglyceride, 총 cholesterol은 굼벵이를 섭취시킴으로써 이의 수치를 감소시켰으며 HDL-cholesterol은 굼벵이의 섭취로 triglyceride 함량은 감소되었다. GOT와 GPT의 활성은 에탄올 투여시 정상식이에 비해 유의적인 증가를 보인 반면, 굼벵이의 섭취로 유의적인 감소를 나타내었다. (p<0.05). 에탄올 추여군의 간조직 세포는 세포질에 지방소적의 축적으로 세포질의 부분적인 괴사현상이 나타났으며 조면소포체와 mitochondria의 형태적 변형이 관찰되었다. 에탄올과 굼벵이의 병용투여군은 지방소적의 크기 및 양적 감소와 세포질의 괴사현상이 약간 회복 되었으나 조면소포체와 mitochondria의 수적인 증가는 미미하였다.