• Journal of Food Hygiene and Safety
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• v.1 no.1
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• pp.1-12
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• 1986

The present studies were undertaken in attempt to investigate the preventive effect of $\beta$-glucan from barley ad diltiazem on cholesterol and vitamin D2 induced-atherosclerotic rat. The results obtained were summerized as follows. 1.The group, fed only the mixture of cholesterol and vitamin D2, showed significant increase of calcium, inorganic phosphorus, total cholesterol, lipid LDL-cholesterol and phospholipid in serum, and total lipid in the liver (p<0.05) as comparing with normal group. The aorta showed severe damage of disorganization, necrosis and lipid deposition in the elastic membrane. 2. The group fed mixture of cholesterol and vitamin D2 plus diltiazem simultaneously, showed significant increase of total cholesterol, total lipid and phospholipid in serum, and total lipid and triglyceride n the liver (p<0.05) as comparing with normal group, but the significant decrease of calcium and inorganic phosphorus in serum(p<0.05) as comparing with the atherogenic control group. The aorta showed slight damage of elastic membrane and lipid deposition as comparing with the atherogenic control group. 3.The group, fed mixture of cholesterol and vitamin D2 puls $\beta$-glucan simultaneously, showed significant decrease of total cholesterol, LDL and VLDL-cholesterol, total lipid, phospholipid and triglyceride in serum, and total lipid in the liver as comparing with the atherogenic control group(p<0.05), but the significant increase of calcium in serum as comparing with the normal group(p<0.05). The aorta showed no changes in elastic fiber and no lipid deposition in comparing with the atherogenic control group.

• Journal of Nutrition and Health
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• v.21 no.3
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• pp.173-181
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• 1988

Various types of evidence suggest that some changes in cellular in cellular calcium may well signal the initiation of a chain of events leading to the physiological effects of the bone resorbing agents. The effects of 1,25-dihydorxycholecalciferol, $1.25\textrm{(OH)}_2\textrm{D}_3$, Ca ionophore A23187 and calcium antagonist, diltiazem on bone resprption and the cellular transport of Ca were investigated. Bone $^{45}\textrm{Ca}$ desaturation experiment was realized in isolated heterogenous rat bone cells after equilibrating the cells with $^{45}\textrm{Ca}$. Results of $^{45}\textrm{Ca}$ desaturation experiments were analysed by fitting the $^{45}\textrm{Ca}$ desaturation curve to a model of 2 exponential terms which indicated the presence of 2 exchangeable cellular calcium pools. $1.25\textrm{(OH)}_2\textrm{D}_3$ (0.5ng/$m\ell$) induced significantly bone resorption which was decreased by the physiological dose of diltiazeme(above 5nmol/$m\ell$) although it was ineffective alone. Ionophore A23187 (0.2$\mu\textrm{g}$/$m\ell$) decreased Ca release from bone but no additivity of effect with diltiazem(20nmol/$m\ell$) was observed. $1.25\textrm{(OH)}_2\textrm{D}_3$ (0.5ng/$10^{6}$ cells) had a moderate effect on the two kinetic phases of $^{45}\textrm{Ca}$ desaturation curve and these values were normalized when diltiazeme (20nmol/$10^{6}$ cells) was added along with $1.25\textrm{(OH)}_2\textrm{D}_3$. Ionophore($0.05\mu\textrm{g}$/$10^{6}$ cells) alone increased specifically the value of the slow turnover rate which was not affected by addition of diltiazem. The hypothesis concerning the involvement of calcium in bone resorption seems in fact to be verified in case of $1.25\textrm{(OH)}_2\textrm{D}_3$ but more unsettled for Ca inophore A23187.

• Journal of Pharmaceutical Investigation
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• v.22 no.3
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• pp.219-227
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• 1992

The influence of phenobarbital (PB) pretreatment (75 mg/kg/day, i.p. for 4 days) on the pharmacokinetics of diltiazem (DTZ) and its metabolite, desacetyldiltiazem (DAD), was investigated in rats. DTZ was injected via femoral (3 mg/kg) or portal (10 mg/kg) vein to the control and PB-pretreated rats. DAD was also injected separately via femoral (3 mg/kg) vein to both groups of rats. The intrinsic hepatic plasma clearance of DTZ was found to be significantly increased (6.8-fold) by the PB pretreatment. However, the fraction of an intravenous DTZ dose converted to DAD $(F_mi)$ was only slightly (6%) increased and calculated metabolic rate constant of DTZ to DAD was not affected by the pretreatment. On the other hand, plasma free fraction of DTZ was increased (1.8-fold) from $4.24{\pm}0.25%$ to $7.45{\pm}0.54%$ by the pretreatment. However, the l.8-fold increase in the free fraction of DTZ would not explain the 6.8-fold increase in the hepatic intrinsic clearance of DTZ. Therefore, the increase in either the hepatic blood flow or the metabolism other than to DAD was expected as the probable mechanism(s) of the increased hepatic clearance of DTZ. Sequential metabolism of DAD to further metabolites, however, would be a more potential cause of the apparently unchanged metabolism of DTZ to DAD by the PB-pretreatment.

• The Korean Journal of Physiology and Pharmacology
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• v.20 no.4
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• pp.399-406
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• 2016

Early life neuronal exposure to environmental toxicants has been suggested to be an important etiology of neurodegenerative disease development. Perfluorohexanesulfonate (PFHxS), one of the major perfluoroalkyl compounds, is widely distributed environmental contaminants. We have reported that PFHxS induces neuronal apoptosis via ERK-mediated pathway. Imperatorin is a furanocoumarin found in various edible plants and has a wide range of pharmacological effects including neuroprotection. In this study, the effects of imperatorin on PFHxS-induced neuronal apoptosis and the underlying mechanisms are examined using cerebellar granule cells (CGC). CGC were isolated from seven-day old rats and were grown in culture for seven days. Caspase-3 activity and TUNEL staining were used to determine neuronal apoptosis. PFHxS-induced apoptosis of CGC was significantly reduced by imperatorin and PD98059, an ERK pathway inhibitor. PFHxS induced a persistent increase in intracellular calcium, which was significantly blocked by imperatorin, NMDA receptor antagonist, MK801 and the L-type voltage-dependent calcium channel blockers, diltiazem and nifedipine. The activation of caspase-3 by PFHxS was also inhibited by MK801, diltiazem and nifedipine. PFHxS-increased ERK activation was inhibited by imperatorin, MK801, diltiazem and nifedipine. Taken together, imperatorin protects CGC against PFHxS-induced apoptosis via inhibition of NMDA receptor/intracellular calcium-mediated ERK pathway.

• The Korean Journal of Pharmacology
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• v.24 no.2
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• pp.203-216
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• 1988

To delineate the mechanisms of vasoconstriction and vasodilation in cerebral arteries the effects of some vasoconstrictors and calcium antagonists on the basilar artery (BA) and arterial circle of Willis (WC) were examined and also the role of endothelium in the action of these drugs was investigated in pigs, cats and rabbits. In pig cerebral arteries, dose-dependent contractile responses were elicited by KCI, histamine, 5-hydroxytryptamine (5-HT) and angiotensin, but norepinephrine (NE), phenylephrine (PE) and epinephrine (EP) elicited dose-dependent contractions only under pretreatment with propranolol 10-6 M. The magnitudes of maximal contractile effects of these drugs were different from each other, and 5-H~ was the largest and angiotensin the smallest. Some calcium antagonists dose-dependently inhibited KCI (35 mM)-induced contraction and the order of potency in inhibiting the contraction was nifedipine > > diltiazem > flunarizine > oxybutynin > isosorbide dinitrate (ISDN) > glyceryl trinitrate. 5-HT (10-6 M)-induced contraction was dosedependently inhibited by nifedipine but slightly inhibited by diltiazem and ISDN. In rings with intact endothelium, KCI (35 mM)-induced contraction was not affected by acetylcholine (ACh) but $PGF_{2{\alpha}}$ (lO-SM)-induced contraction was dose-dependently relaxed by ACh and adenosine. This endothelium-dependent relaxation was not affected by nifedipine (l0-6M)-pretreatment but markedly inhibited by methylene blue (50,uM)-pretreatment. In the porcine arterial rings without endothelium, ACh had no effect or even contracted the $PGF_{2{\alpha}}-induced$ contraction. However, the dosedependent relaxing effect of ACh appeared when the deendothelized porcine ring and rabbit thoracic aorta with intact endotheli urn were simultaneously suspended into a bath and this relaxing effect was also inhibited by methylene blue-pretreatment. In cat cerebral arteries, 5-HT and NE elicited dose-dependent contractile responses and ACh also produced dose-dependent contraction regardless of the existence of endothelium. ACh-induced contraction was most prominent. 5-HT (IO-SM)induced contraction was not relaxed but contracted additionally by ACh even in the intact endothelial ring. In rabbit cerebral arteries, 5-HT and NE elicited dose-dependent contractile responses and 5-HT-induced contraction was more prominent. In the intact endothelial preparations, 5-HT (lO-s M)-induced contraction was markedly relaxed by the addition of ACh( IO-SM) and this endothelium-dependent relaxing effect was inhibited by atropine (l0-7M)-pretreatment but notaffected by diltiazem (l0-6M)-pretreatment. These results suggest that ACh elicits endotheliumdependent relaxing effect mediated by muscarinic receptors in cerebral arteries of pig and rabbit, and that ACh acts as vasoconstrictor in cat cerebral artery.

• Radiation Oncology Journal
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• v.17 no.3
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• pp.230-237
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• 1999

Purpose : To elucidate the effects of pentoxifylline and diltiazem on the late response of the salivary glands of the rat after irradiation. Materials and Methods : Sixteen Sprague-Dawley rats were divided into 4 groups : (a) irradiation alone (b) irradiation with pentixifylline (PTX) (c) irradiation with diltiazem (DTZ) (d) irradiation with both PTX and DTZ. Irradiation was given in a single fraction of 16 Gy using 4 MV photon energy through an anterior port encompassing the left side of the salivary gland leaving the right side of salivary gland as a control. PTX, 20 mg/kg and/or DTZ, 50 mg/kg were infused intraperitoneally before irradiation, Two rats from each group were sacrificed on the 10th week and the rest was sacrificed on the 16th week after irradiation. Histopathologic examinations were undertaken for each section and the proportion of vacuolated cells out of the total number of cells under light microscopic fields was calculated. The statistical significance in the difference of the proportion of the vacuolated cells among the experimental groups was evaluated by a $x^2$-test. Results : Irradiated salivary glands of the 10th week group revealed markedly increased number of vacuolated cells compared to those of unirradiated control. The proportion of vacuolated cells was significantly reduced in both the PTX group (p value=0.001) and the combined PTX and DTX group compared to those of irradiation alone group. The DTZ alone group did not reveal the significant reduction of vacuolated cells compared to those of irradiation alone group (p value, >0.05). The 16th week groups revealed similar findings to those of the 10th week group, but the degree of chronic inflammatory cell infiltrates and interstitial fibrosis was increased and the number of acinar cells was reduced compared to those of the 10th week group. Conclusions : PTX significantly reduced the late radiation response of salivary glands, but DTZ did not reduce the same degree as PTX did. Taking the positive results of this study into consideration, it seems reasonable to apply PTX into the clinical trial for the head and neck irradiation to reduce the late radiation sequelae of salivary glands in the near future. At the same time the further experiment to clarify the subcellar mechni는 involved in PTX should be preceded.

• 대한임상약리학회:학술대회논문집
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• 1997.12a
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• pp.36-37
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• 1997

• 대한임상약리학회:학술대회논문집
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• 1992.11a
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• pp.28-28
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• 1992

• Korean Journal of Clinical Pharmacy
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• v.14 no.2
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• pp.91-95
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• 2004

당뇨환자가 합병증으로 고혈압이 있을 경우 항고혈압약물인 딜티아젬을 투여시 딜티아젬의 동태학적 측면에서 투여계획을 설계하기 위해서 토끼에 알록산을 당뇨병모델을 만들었다. 알록산으로 유도된 급성 및 만성 당뇨 토끼에서 딜티아젬의 약물동태 변화에 대한 결과는 당므과 같다. 1. Alloxan 45 mg/kg을 토끼의 귀정맥에 투여시 혈당농도는 control군에서 $112\pm20.6\;mg/dl$, acute DM군에서는 $260\pm897\;mg/dl$, chronic DM군에서는 $331\pm85\;mg/dl$으로 당뇨가 유발되었음이 확인되었다.. 2. Alloxan에 의한 당뇨병 유발토끼에서 딜티아젬의 혈중농도곡선하면적(AUC)값은 대조군$(21.6\pm2.45\;\mug/ml)$ 보다 chronic DM군$(31.91\pm379\;mg/ml{\cdot}hr)$에서 유의성(p<0.05) 있게 증가하였다. 3. 딜티아젬의 요중누적배설량은 대조군에 비해 acute 및 chronic DM군에서 감소되었으나 유의성은 없었다. 4. 당뇨병 유발 토끼에서 딜티아젬의 토탈바디클리어런스$(CL_t)$ 값과 $\beta$-소실속도정수값이 대조군에 배해서 유의성(p<0.05)있게 감소되었다. 실험적 당뇨 토끼에서 딜티아젬의 생체이용률의 증가는 딜티아젬의 토탈바디클리어런스$(CL_t)$ 값과 베타의 소실속도정수 값이 대조군에 비해서 유의성있게 감소되었기 때문으로 사료된다.

• 전기의세계
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• v.41 no.12
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• pp.21-30
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• 1992

내연기관의 가솔린자동차보다 역사가 오래된 전기자동차는 상대적으로 주생성능과 가격 경쟁력의 열세로 그 자취를 감추었고 최근까지 주로 특수목적의 단거리 저속차량으로 사용되고 있다. 그러나 1890년대 후반부터 전세계가 자동차배기가스에 의한 대기오염과 지구온난화 현상등의 문제를 심각하게 공감하게 되었고 마침내 미국 캘리포니아주에서는 전가자동차의 강제판매를 규정화하게 이르렀다. 이 규정에 의하면 1998년도부터 차량 판매대수의 2%를 전기자동차 판매로 강제요구하고 있다. 이 비율은 2000녀도에 5% 2003년에는 10%로 늘어날 계획이다. 따라서 미국에 많은 자동차를 수출하고 있는 일본, 독일 및 여러 유럽국가에서는 이 사업에 막대한 자금을 투자하며 개발에 몰두하고 있다. 미국의 Big3도 에너지성의 도움으로 최근 USABC를 결성하여 전기자동차 개발에 박차를 가하고 있다. 지금까지 기존의 가솔린자동차 기술에 있어서 일본과 독일에 상대적 열세에 있었던 미국도 이번 캘리포니아주의 전기자동차 강제판매 규정에 따른 전기자동차 사업으로 미국자동차 시장의 새로운 판도를 조성하겠다는 의도인듯하다. 국내에서도 정부가 이 사업의 중요성을 심각히 인식하고 G7사업과제의 하나로 선정하여 산, 학, 연 각층의 전문가가 참여하여 성공적으로 개발을 마칠 수 있도록 적극 지원하고 있다. 지금까지의 평균주행성능을 보면 최고속도 100-120km/h, 일층전 최대주행거리 150-200km 정도이며, 아직 양산체제에 돌입하지 않았기 때문에 가격면에서 경쟁력이 없는 실정이다. 그러나 1990년도에 들면서 각종 요소부품들의 기술수준이 급성장을 이루어서 앞으로 10년정도 후면 성능과 가격면에서 가솔린자동차와 대등한 수준의 전기자동차 개발이 실현될 수 있으리라 예측된다.는 영향받지 않았다. Clonidine의 심박수 감소작용은 .뇌실내및 정맥내 diltiazem이나 nifedipine 처리후에 감약되었다. 5). 뇌실내 clonidine$(30{\mu}g)$ 처 리후 뇌실내 diltiazem$(400{\mu}g)$과 nifedipine$(350{\mu}g)$의 혈압하강및 심박수 감소효과는 영향 받지 않고 그대로 나타났다. 이상의 결과로 diltiazem과 nifedipine은 가토뇌내에서 methoxamine에 의한 혈압상승의 작용점인 alrfia-1 adrenoceptor의 흥분에는 영향을 미치지 못하나 clonidine의 작용점인 alpha-2 adrenoceptor의 흥분에 의한 혈압하강및 심박수 감소효과는 억제한다고 추론하였다.thin 함량은 110.6 mg/L로서 산업적인 생산성이 있는 것으로 나타났다. 이번 연구를 통하여 개발된 변이주 B76 및 이의 대량 발효를 위한 최종조건의 정립은 향후 astaxanthin의 산업적 생산공정에 필요한 기초자료로 이용될 것으로 기대된다.색총말내에 소형의 도형, 소형의 장형 연접소포 및 DENSE CORE VESICLE의 3가지 연접소포를 가지고 있었고 출현빈도수는 촉각엽에서 가장 큰 33%이었다. 제5형 신경연접은 축색종말내에 중등도크기의 원형, 대형의 원형연접소포 및 DENSE CORE VESICLE을 포함하였고 13%의 출현빈도수로 관찰되었다. 배추횐나비의 촉각에 있는 지각신경세포가 뇌의 촉각엽으로 뻗어 들어가 위의 5가지 신경연접중 어느 형을 형성하는지를 관찰하기 위하여 좌측 촉각의 기부를 제거하여 지각신경세포를 절단하였는데 그 결과, 좌측 촉각엽에서 제4형의 신경연접이 퇴행성 변화를 나타내었다.