• Journal of Korean Traditional Oncology
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• v.11 no.1
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• pp.75-93
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• 2006

Jiaweicitaowan (JWCTW) has been used to inhibit recurrence and metastasis of cancer in clinical practice. Further study has shown its anti-metastatic and anti-angiogenic effects. By applying in vitro and in vivo anti-angiogenic evaluation model, the author assayed the each ingredients of JWCTW. The author performed the following experiments and the results are listed as below: Cell viability assay showed that the viability was almost identical between that of the control and that of the ingredients extract 40 ${\mu}g/m{\ell}$ treated, except of hexane fraction of Curcumae Radix (40 ${\mu}g/m{\ell}$, 2.0% of control), ethylacetate fraction (40 ${\mu}g/m{\ell}$, 26.7%), butanol fraction (20 ${\mu}g/m{\ell}$, 87.2%; 40 ${\mu}g/m{\ell}$, 12.5%) of Cremastrae appendiculatae Tuber, water fraction of Persicae Semen (40 ${\mu}g/m{\ell}$, 82.7%), ethylacetate fraction of Hippocampus (40 ${\mu}g/m{\ell}$, 85.3%). The results of gelatin zymogram assay showed that the ingredients of JWCTW decreases the gelatinolytic activity of MMP-9 from ECV304, at the concentration of 10 ${\mu}g/m{\ell}$. In in vitro invasion assay, the ingredients of JWCTW effectively inhibited the invasion of cancer cells as compared with the control (+PMA) groups. In capillary-like tube formation assay, the hexane and ethylacetate fractions of Curcumae Radix, Cremastrae appendiculatae Tuber and Persicae Semen showed the dramatic inhibition effects on tube formation of ECV304 at the concentration of 40 ${\mu}g/m{\ell}$. In ex vivo rat aortic ring assay, the hexane and ethylacetate fractions of Curcumae Radix, Cremastrae appendiculatae Tuber and Persicae Semen showed the inhibition effects on angiogenesis of rat aorta at the concentration of 40 ${\mu}g/m{\ell}$. According to the above research, the anti-angiogenic effects of the ingredients of JWCTW was proved and it suggested that the more effective prescription for anti angiogenesis could be developed.

• Clinical and Experimental Pediatrics
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• v.48 no.8
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• pp.901-906
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• 2005

Kawasaki disease (KD) is a leading cause of acquired heart disease in children. Yet the etiology of KD is still unknown and diagnosis depends on the exclusion of other diseases and the clinical manifestations meeting the defined criteria. Young infants frequently show atypical clinical courses and are frequently complicated with coronary aneurysms. Some cases show thrombocytopenia, which is known as one of the risk factors for complications with coronary aneurysms. So, a high index of suspicion is the most important factor for the diagnosis of KD in very young infants or adolescents whose clinical courses are equivocal. We report herein on a case of KD in an 80-day-old female infant with fever and seizure with bloody stool; laboratory findings were those of sepsis with disseminated intravascular coagulopathy. In spite of aggressive treatments, fever and thrombocytopenia persisted for two weeks and huge coronary aneurysms developed at the third week in all three major coronary arteries; the diameter of the right one was as large as the aortic annulus. Three months later, huge pulsatile masses developed in both axillas; these were found to be huge axillary aneurysms defined very clearly on multi-detector CT scan. She has been under follow up with antiplatelets and anticoagulation therapy with poor regression of the aneurysms.

• The Korean Journal of Physiology and Pharmacology
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• v.9 no.2
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• pp.117-123
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• 2005

A cumulative evidence indicates that consumption of tea catechin, flavan-3-ol derived from green tea leaves, lowers the risk of cardiovascular diseases. However, a precise mechanism for this cardiovascular action has not yet been fully understood. In the present study, we investigated the effects of different green tea catechins, such as epigallocatechin-3 gallate (EGCG), epigallocatechin (EGC), epicatechin-3 gallate (ECG), and epicatechin (EC), on angiotensin II (Ang II)-induced hypertrophy in primary cultured rat aortic vascular smooth muscle cell (VSMC). [$^3H$]-leucine incorporation was used to assess VSMC hypertrophy, protein kinase assay, and western blot analysis were used to assess mitogen-activated protein kinase (MAPK) activity, and RT-PCR was used to assess c-jun or c-fos transcription. Ang II increased [$^3H$]-leucine incorporation into VSMC. However, EGCG and ECG, but not EGC or EC, inhibited [$^3H$]-leucine incorporation increased by Ang II. Ang II increased phosphorylation of c-Jun, extracellular-signal regulated kinase (ERK) 1/2 and p38 MAPK in VSMC, however, EGCG and ECG , but not EGC or EC, attenuated c-Jun phosphorylation increased by Ang II. ERK 1/2 and p38 MAPK phosphorylation induced by Ang II were not affected by any catechins. Ang II increased c-jun and c-fos mRNA expression in VSMC, however, EGCG inhibited c-jun but not c-fos mRNA expression induced by Ang II. ECG, EGC and EC did not affect c-jun or c-fos mRNA expression induced by Ang II. Our findings indicate that the galloyl group in the position 3 of the catechin structure of EGCG or ECG is essential for inhibiting VSMC hypertrophy induced by Ang II via the specific inhibition of JNK signaling pathway, which may explain the beneficial effects of green tea catechin on the pathogenesis of cardiovascular diseases observed in several epidemiological studies.

• The Korean Journal of Physiology and Pharmacology
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• v.22 no.6
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• pp.607-616
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• 2018

The effect of melatonin on juveniles with cardio fibrosis is poorly understood. We investigated whether HDACs participate in the anti-fibrotic processes regulated by melatonin during hypertrophic remodeling. Abdominal aortic constriction (AAC) was employed in juvenile rats resulting in pressure overload-induced ventricular hypertrophy and melatonin was subsequently decreased via continuous light exposure for 5 weeks after surgery. AAC rats displayed an increased cross-sectional area of myocardial fibers and significantly elevated collagen deposition compared to sham-operated rats, as measured by HE and Masson Trichrome staining. Continuous light exposure following surgery exacerbated the increase in the cross-sectional area of myocardial fibers. The expression of HDAC1, HDAC2, HDAC3, HDAC4 and HDAC6 genes were all significantly enhanced in AAC rats with light exposure relative to the other rats. Moreover, the protein level of $TNF-{\alpha}$ was also upregulated in the AAC light exposure groups when compared with the sham. However, Smad4 protein expression was unchanged in the juveniles' hearts. In contrast, beginning 5 weeks after the operation, the AAC rats were treated with melatonin (10 mg/kg, intraperitoneal injection every evening) or vehicle 4 weeks, and sham rats were given vehicle. The changes in the histological measures of cardio fibrosis and the gene expressions of HDAC1, HDAC2, HDAC3, HDAC4 and HDAC6 were attenuated by melatonin administration. The results reveal that melatonin plays a role in the development of cardio fibrosis and the expression of HDAC1, HDAC2, HDAC3, HDAC4 and HDAC6 in cardiomyocytes.

• Journal of Nutrition and Health
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• v.25 no.6
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• pp.476-484
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• 1992

The influence of selenuium deficiency and fish oil on lipid peoxidation status and fatty acid composition of tissues(plasma aorta and liver) was studied. Male Sprague Dawley rats were fed for eight weeks semipurified diets containing 7% corn oil(by weight) or 5, 5% fish oil(MaxEPA) plus 1.5% corn oil with oil with or without selenium status (glutathione peroxidase activity and selenium levels) were significantly lower in the rats given inadequate selenium in plasma aorta (p<0.02 and p<0.001 respectively) gut not that in plasma Selenium supplementation decreased hepatic MDA levels(p<0.02) Increases in the levels of 20:5(n-3) 22:5(n-3), 22:6(n-3) 20:3(n-6) and a decrease in the level of 20:4(n-6) were observed in plasma total lipids and aortic and hepatic phospholipids when fish oil was fed. Though selenium supplementation increased the level of n-3 fatty acids(such as 22:6(n-3)) in plsama and the aorta is overall effect was smaller than the effect of fish oil feeding. These data suggest that selenium may play a significant but minor role in protecting against lipid peroxide-tion even when vitamin E intakes are in excess of current recommendations in both corn oil and fish oil diets.

• Clinical and Experimental Pediatrics
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• v.45 no.2
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• pp.208-213
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• 2002

Purpose : The major cause of cardiac dysfunction, after open heart surgery for congenital heart disease, is perioperative myocardial injury. Cardiac troponin I is found only within the myocardial cell, so it can be used as a biochemical marker of the myocardial injury. We performed this study to evaluate the worth of cardiac troponin I as a biochemical marker reflecting the extent of perioperative myocardial injury and recovery. Methods : Thirty-four patients who had undergone elective open heart surgery of congenital heart disease(CHD) from April to July 2001 were enrolled in this study. We measured types of CHD, serial cardiac troponin I(baseline 1 day before operation, postoperative day 1, 2, 3, 7), duration of cardiopulmonary bypass(CPB), aortic cross clamping(ACC), intubation and postoperative hospital stay. Results : Compared with the baseline before operation, there was a significant, increase of cardiac troponin I on the postoperative day 1 and a significant gradual decrease on the day 2, 3, 7. The levels of cardiac troponin I were the highest in the transposition of great artery(TGA) repair on the postoperative day 1 and high in the tetralogy of Fallot(TOF), atioventricular septal defect (AVSD), ventricular septal defect(VSD) and atrial septal defect(ASD) repair with decreasing sequence. The longer duration of CPB, ACC and intubation, the higher of cardiac troponin I, but there were no significant correlations between cardiac troponin I levels and duration of hospital stay. Conclusion : Because there was significant increases or decreases of cardiac troponin I according to the perioperative time and types of the congenital heart disease, it is a worthy biochemical marker which reflects the extent of perioperative myocardial injury and recovery after open heart surgery.

• The Korean Journal of Pharmacology
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• v.27 no.2
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• pp.125-133
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• 1991

In the isolated rabbit mesenteric artery denuded of endothelium, we characterized the identity of the A23187-induced endothelium-dependent relaxing factor (EDRF) released from the endothelium of rabbit aorta, which is distinct from that of acetylcholine-induced relaxing factor. In the normal physiological salt solution (PSS), the dose-response curves to A23187 and acetylcholine were overlapped together. Their effects were also inhibited by methylene blue. Upon application of hypoxanthine and xanthine oxidase into the bath, the phenylephrine-induced precontraction was transiently increased followed by the sustained relaxation. During the burst of hypoxanthine-xanthine oxidase reaction, the $Ca^{++}$ ionophore, A23187 but not acetylcholine was able to cause an immediate relaxation. However, A23187-induced relaxation was not manifested when precontracted by 50 mM $K^+-PSS$. Nevertheless, in the presence of superoxide dismutase, A23187 could produce an immediate relaxation without accompanying the transient contraction as acetylcholine did during the hypoxanthine-xanthine oxidase reaction. On the other hand, acetylcholine-induced relaxation was more sensitively inhibited by phorbol 12-myristate 13-acetate (PMA) than A23187-induced relaxation. Endothelium-independent relaxation to sodium nitroprusside was not affected by PMA. Based on these results it is suggested that both A23187 and acetylcholine cause the methylene blue-inhibitable endothelium-dependent relaxation, and in addition, A23187 may release a stable EDRF which is resistant to superoxide anion and PMA.

• The Korean Journal of Physiology and Pharmacology
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• v.1 no.5
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• pp.529-535
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• 1997

The present study was aimed at investigating whether the vascular calcium regulation is altered in hypertension. Two-kidney, one clip (2K1C) and deoxycorticosterone acetate (DOCA)-salt hypertension were made in rats, and their thoracic aortae were taken 4 weeks later. The isometric contractile response and calcium uptake of the endothelium-denuded aortic preparations were determined. Caffeine ($0.1{\sim}35\;mmol/L$) induced a greater contraction in 2K1C and DOCA-salt hypertension than in normotensive control. When the vascular calcium store was functionally-depleted by a repeated exposure to caffeine, it took longer to reload the store and to resume the initial contraction force in response to caffeine in both 2K1C and DOCA-salt hypertension. The vascular $^{45}Ca$ uptake following the functional depletion of the cellular store was also greater in both models of hypertension than in control. Ryanodine, calcium channel activator of the sarcoplasmic reticulum, attenuated the restoration of caffeine-induced vascular contraction, which was not affected by either 2K1C or DOCA-salt hypertension. Nifedipine, an L-type $Ca^{2+}$ channel blocker, attenuated the restoration of caffeine-induced contraction, which was not affected by DOCA-salt hypertension, but was more pronounced in 2K1C hypertension. Nifedipine also diminished the vascular $^{45}Ca$ uptake, which was not affected by DOCA-salt hypertension, but was more pronounced in 2K1C hypertension. Ouabain, a $Na^+,\;K^+-ATPase$ inhibitor, increased the caffeine-induced contraction by a similar magnitude in control and 2K1C hypertension, which was, however, markedly attenuated in DOCA-salt hypertension. Ouabain enhanced the vascular $^{45}Ca$ uptake, the degree of which was not affected by 2K1C hypertension, but was markedly attenuated in DOCA-salt hypertension compared with that in control. Cyclopiazonic acid, a selective inhibitor of $Ca^{2+}-ATPase$ of the sarcoplasmic reticulum, attenuated the restoration of caffeine-induced contraction, which was not affected by 2K1C hypertension, but was more marked in DOCA-salt hypertension. These results suggest that the increased vascular calcium storage may be attributed to an enhanced calcium influx in 2K1C hypertension, and to an impaired $Na^+-K^+$ pump activity of the cell membrane and subsequently increased calcium pump activity of the cellular store in DOCA-salt hypertension.

• The Korean Journal of Pharmacology
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• v.30 no.3
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• pp.337-342
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• 1994

It is well known that angiotensin converting enzyme inhibitors(ACEIs) increase endothelium-dependent relaxation in aortic strips of spontaneously hypertensive rats(SHR) and this increase in relaxation may be due to altered endothelial nitric oxide breakdown. But there are few studies on the effect of the angiotensin II receptor blocker on the nitric oxide-mediated relaxation. So we attempted to investigate the effect of angiotensin II receptor blocker on the nitric oxide-dependent relaxation in isolated aorta of SHR. Two week-treatment of losartan (30 mg/kg/day) increased the acetylcholine$(10^{-9}\;to\;10^{-5}\;M)$-and histamine$(10^{-8}\;to\;10^{-4}\;M)$-induced relaxation in endothelium intact strips but 90 minutes-treatment of losartan $(10^{-4}\;M)$ showed no increase in relaxation. The phenylephrine $(10^{-7}\;M)$-induced contraction, repeated every 2 hours, was diminished gradually following lipopolysaccharide (LPS)-treatment $(100\;{\mu}g/ml)$ but there was no significant difference in enalapril- and losartan-treated group compared with control group. These results suggest that activity of the endothelial constitutive NO synthase may be changed by chronic treatment of angiotensin II receptor blockers and ACEIs but angiotensin II antagonist and ACEI have no effect on the inducible NO synthase activity in the isolated aorta of SHR

• The Korean Journal of Physiology
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• v.24 no.1
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• pp.91-102
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• 1990

The effects of extracellular $Ca^{2+}$ and various $Ca^{2+}$ antagonists on endothelium-dependent relaxation to acetylcholine were studied in the isolated rabbit thoracic aorta in order to elucidate the control mechanism of endothelium derived relaxing factor (EDRF) release. Endothelium was removed from aortic strips by gentle rubbing with cotton ball. The effect of hemoglobin on basal tension was also observed with hemolysate. The results obtained were as follows: 1) Endothelium-dependent relaxation (EDR) to acetylcholine (ACh) showed biphasic pattern; the initial rapid relaxation phase and the late slow relaxation phase. 2) With the depletion of the extracellular $Ca^{2+}$, EDR was gradually suppressed, especially the late slow relaxation. 3) Verapamil, nifedipine, $Mn^{2+}$ and $Cd^{2+}$ had not any effect on EDR, while $La^{3+}$ and $Co^{2+}$ suppressed EDR completely. 4) The resting tension of the strips with rubbed endothelium was not altered by the addition of hemoglobin. That of the strips with intact endothelium, however, was enhanced and EDR to ACh was completely blocked From these results, we suggest that extracellular $Ca^{2+}$ is necessary for ACh-induced slow relaxation while $Ca^{2+}$ antagonists have not any effect on EDR.