• The Korean Journal of Pharmacology
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• v.23 no.2
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• pp.123-131
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• 1987

The possible inolvement of central opiate system in the control of cardiovascular function and in the antihypertensive action of clonidine has been examined in unanesthetized rats with shamoperated or 2-kidney, 1-clip (2K1C) renal hypertension. In both groups of rats, intraventricular clonidine $(3-30\;{\mu}g/kg)$ produced hypotension and bradycardia. Hypotensive action of clonidine was more potent in the hypertensive rats than in the normotensive sham-operated rats. Yohimbine $(30\;{\mu}g/kg,\;i.v.t.)$ inhibited the hypotension and bradycardia produced by clonidine. Naloxone ($50\;{\mu}g/kg$, i.v.t.) inhibited the action of clonidine in 2K1C hypertensive rats but not influenced in the sham-operated rats. Intraventricular morphine $(10-100\;{\mu}g/kg)$ also reduced rats. Intraventricular morphine $(10-100\;{\mu}g/kg)$ also reduced blood pressure and heart rate in both groups of rats. But these effects were not affected by yohimbine, but antagonized by naloxone ($50\;{\mu}g/kg$, i.v.t.). Chronic treatment of 2K1C rats with clonidine ($3{\times}20\;{\mu}g/kg$, p.o.,) for 14 days from 1 day after 2K1C operation) suppressed the development of hypertension and maintained the blood pressure in normal level and this errect of clonidine was abolished by naloxone (2 mg/kg, i. p.). In the 2K1C hypertensive rats, immunoreactive ${\beta}-endorphin$ content was significantly decreased, but maximum binding (Bmax) of $(^3H)-naloxone$ was significantly increased in brain of 2K1C hypertensive rats. However, Kd value was not changed. These results suggest that the opioidergic component might be involved in the antihypertensive action of clonidine only in hypertensive and that central opiate system might play important roles in pathophysiology of development and maintenance of hypertension.

• Journal of Chest Surgery
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• v.40 no.4 s.273
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• pp.264-272
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• 2007

Background: Vascular endothelial growth factor (VEGF) plays an important role in angiogenesis, including stimulating the proliferation and migration of vascular smooth muscle cells (VSMCs). It has been known that diabetes is associated with accelerated cellular proliferation via VEGF, as compared to that under a normal glucose concentration. We investigated the effects of selective blockade of a VEGF receptor by using anti-Flt-1 peptide on the formation and hyperplasia of the neointima in balloon injured-carotid arteries of OLETF rats and also on the in vitro VSMCS' migration under high glucose conditions. Material and Method: The balloon-injury method was employed to induce neointima formation by VEGF. For f4 days beginning 2 days before the ballon injury, placebo or vascular endothelial growth factor receptor-1 (VEGFR-1) specific peptide (anti-Flt-1 peptide), was injected at a dose of 0.5mg/kg daily into the OLETF rats. At 14 days after balloon injury, the neointimal proliferation and vascular luminal stenosis were measured, and cellular proliferation was assessed by counting the proliferative cell nuclear antigen (PCNA) stained cells. To analyze the effect of VEGF and anti-Flt-1 peptide on the migration of VSMCs under a high glucose condition, transwell assay with a matrigel filter was performed. And finally, to determine the underlying mechanism of the effect of anti-Flt-1 peptide on the VEGF-induced VSMC migration in vitro, the expression of matrix metalloproteinase (MMP) was observed by performing reverse transcription-polymerase chain reaction (RT-PCR). Result: Both the neointimal area and luminal stenosis associated with neointimal proliferation were significantly decreased in the anti-Flt-1 peptide injected rats, ($0.15{\pm}0.04 mm^2$ and $ 36.03{\pm}3.78%$ compared to $0.24{\pm}0.03mm^2\;and\;61.85{\pm}5.11%$, respectively, in the placebo-injected rats (p<0.01, respectively). The ratio of PCNA(+) cells to the entire neointimal cells was also significantly decreased from $52.82{\pm}4.20%\;to\;38.11{\pm}6.89%$, by the injected anti-Flt-1 peptide (p<0.05). On the VSMC migration assay, anti-Flt-1 peptide significantly reduced the VEGF-induced VMSC migration by about 40% (p<0.01). Consistent with the effect of anti-Flt-1 peptide on VSMC migration, it also obviously attenuated the induction of the MMP-3 and MMP-9 mRNA expressions via VEGF in the VSMCS. Conclusion: Anti-Flt-1 peptide inhibits the formation and hyperplasia of the neointima in a balloon-injured carotid artery model of OLETF rats. Anti-Flt-1 peptide also inhibits the VSMCs' migration and the expressions of MMP-3 and MMP-9 mRNA induced by VEGF under a high glucose condition. Therefore, these results suggest that specific blockade of VEGFR-1 by anti-Flt-1 peptide may have therapeutic potential against the arterial stenosis of diabetes mellitus patients or that occurring under a high glucose condition.

• The Journal of Korean Obstetrics and Gynecology
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• v.30 no.2
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• pp.49-70
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• 2017

Objectives: The present study is to observe the skin-regeneration, anti-wrinkle, whitening and skin moisturizing effects of Cheongsangbangpung-tang (CSBPT) with cytotoxicity. Methods: In the present study, cytotoxicity of CSBPT lyophilized aqueous extracts (yield=18.71%) was experimented against human normal fibroblast cells and B16F10 murine melanoma cells by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium Bromide (MTT) assay, and skin regeneration and anti-wrinkle effects were also showed through the assay of collagen type I synthesis by an enzyme immunoassay (EIA) kit as comparing with transforming growth factor (TGF)-${\beta}1$, hyaluronidase, collagenase and matrix metalloproteinase (MMP)-1 inhibitory assays as comparing with oleanolic acid (OA), and elastase inhibitory effects as comparing with phosphoramidon disodium salt (PP). In addition, whitening effects of CSBPT were observed by tyrosinase inhibitory assay and melanin formation test in B16/F10 melanoma cells as comparing with arbutin, and skin moisturizing effects were measured through mouse skin water contents test, respectively. Results: No CSBPT treatment related cytotoxic effects were demonstrated against human normal fibroblast cells and B16/F10 murine melanoma cells. CSBPT concentration-dependent increased collagen type I synthesis at human normal fibroblast cells. It also effectively suspreessed hyaluronidase, collagenase, elastase and MMP-1 activities, which were enzymes that related to declining of ECM and formation of wrinkle. CSBPT supressed B16/F10 melanoma cells's melanin productions with tyrosinase activity, which was an enzyme connected with melanin formation, and dose-dependent and significant increases of skin water contents were detected in CSBPT treated mouse skin as compared with vehicle control skins. Conclusions: CSBPT showed favorable and enough skin regeneration, anti-wrinkle, whitening and skin moisturizing effects at least in a condition of this experiment. However, more detail mechanism and in vivo skin protective efficacy studies should be conducted in future with the screening of the biological active compounds in individual herbs of Cheongsangbangpung-tang.

• Korean Journal of Veterinary Research
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• v.41 no.3
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• pp.437-445
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• 2001

This study was performed to validate the procedure of transarterial embolization of the renal artery (TAE-RA) using iohexol-ethanol solution in dogs with unilateral experimental hydronephrosis and to evaluate the embolized kidney using B-mode ultrasonography and selective angiography. Experimental hydronephrosis was induced by ligation of unilateral ureter in 12 dogs. Ultrasonographic findings revealed that size of the kidney was significantly increased at 9 days and 17 days and the length of renal cortex was significantly decreased at 17 days after ligation of the unilateral ureter and it was in accordance with dilation of ipsilateral renal pelvis. No significant change of BUN, creatinine, ALT, calcium, and phosphorus was found immediately after unilateral experimental hydronephrosis. Therefore, it was concluded that unilateral hydronephrosis was established in 12 dogs at 17 days after ligation of ureter. Renal artery embolization was performed using selective catheterization in the hydronephrotic kidney of seven dogs and EKG, $SpO_2$, body temperature, pulse, and respiratory rate were within normal ranges during procedures. Iohexol-ethanol solution was used as embolic material. Average ethanol dose for renal artery embolization was $1.94{\pm}1.24ml/kg$. There were no dogs expired after TAE-RA and no side effects associated with regurgitation of iohexol-ethanol solution. Revascularization of renal artery was not found in angiography in dogs treated by TAE-RA at immediately after TAE-RA and 14 days after TAE-RA. Ultrasonographically, the mean longitudinal length of the embolized kidney decreased significantly at 2 and 3 months after TAE-RA compared to that of contralateral normal kidney. In summary, marked shrinkage of the embolized kidney was observed in dogs with unilateral experimental hydronephrosis treated by TAE-RA with iohexol-ethanol and no adverse effects were observed throughout the observation period. It is concluded that TAE-RA with iohexol-ethanol solution is a viable alternative to nephrectomy in dogs with unilateral hydronephrosis.

• Tuberculosis and Respiratory Diseases
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• v.56 no.2
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• pp.187-197
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• 2004

Background : Nitric Oxide (NO) is a multi-faceted molecule with dichotomous regulatory roles in many areas of biology. NO can promote apoptosis in some cells, whereas it inhibits apoptosis in other cell types. This study was performed to characterize NO-induced cell death in lung epithelial cells and to investigate the roles of cell death regulators including iron, bcl-2 and p53. Methods : A549 cells were used for lung epithelial cells. SNP (sodium nitroprusside) and SNAP (S-nitroso-N-acetyl- penicillamine) were used for NO donor. Cytoxicity assay was done by MTT assay and crystal violet assay. Apoptotic assay was done by fluorescent microscopy after double staining with propidium iodide and hoecst 33342. Iron inhibition study was done with RBCs and FeSO4. For bcl-2 study, bcl-2 overexpressing cells (A549-bcl-2) were used and for p53 study, Western blot analysis and p53 functionally knock-out cells (A549-E6) were used. Results : SNP and SNAP induced dose-dependent cell death in A549 cells and fluorescent microscopy revealed that SNAP induced apoptosis in low doses but necrosis in high doses while SNP induced exclusively necrotic cell death. Iron inhibition study using RBCs and FeSO4 significantly blocked SNAP-induced cell death. And also SNAP-induced cell death was blocked by bcl-2 overexpression. Finally, we found that SNAP activate p53 by Western blot analysis and that SNAP-induced cell death was decreased in the abscence of p53. Conclusion : In lung epithelial cells, NO can induce cell death, more precisely apoptosis in low doses and necrosis in high doses. And iron, bcl-2, and p53 play important roles in NO-induced cell death.

• Journal of Korean Society of Forest Science
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• v.84 no.1
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• pp.103-113
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• 1995

To estimate buffer capacity and sensitivity of forest ecosystem to acid rain in Taejon, ionic components of throughfall, stemflow, soil leachate, and open rain in Pinus rigida and Quercus variabilis forest were analysed. The spatial sensitivity based on parent rock and forest type was given by IDRISI of GIS which created imagery conversion from soil and vegetation map. Parent rocks and soils were classified into acidic, sedimentary, metamorphic rock and then subdivided based on $SiO_2$ content. Average pH of vegetation leachate was higher in throughfall but lower in stemflow than open rain and higher in Quercus variabilis forest than in Pinus rigida forest. The flow of $SO{_4}^{2-}$, $NO_3{^-}$ and $Cl^-$ through vegetation leaching(throughfall plus stemflow) into soil were 7.2, 4.3, and 2.5 times, respectively, higher in Pinus rigida forest and 4.4, 2, and 2.5 times, respectively, higher in Quercus variabilis forest than in open field. But the concentration of exchangeable cations was 4.1 times higher in Pinus rigida forest and 4.6 times higher in Quercus variabilis forest than in open field. Average pH of soil leachate was lower than that of throughfall, but higher than that of stemflow. The concentration of exchangeable canons and $Al^{3+}$ in soil leachate were more in Pinus rigida forest than in Quercus variabilis forest and increase signficantly with the increase of acidic deposits. Pinus forest had more deposition and canopy interception of acidic pollutants and more nutrient loss than Quercus forest, and Quercus forest had more cation exchange and proton consumption and than consequently had less nutrient loss and better buffer capacity than Pinus forest. The 69% of forest soils was distributed on acidic rock, 25% of it on metamorphic rock, and 6% of it on intermediate and basic rock. Acidic rock residuals which had low very canon exchange capacity and high sensitivity to acid rain occupied a half of total forest land in Taejon area. Therefore forests in Taejon showed high vulnerability to acid rain and will receive much more stress with the increase of acid rain precursors.

• The Korean Journal of Pharmacology
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• v.32 no.1
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• pp.67-74
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• 1996

Cholecystokinin octapeptide (CCK-8), acetylcholine (ACh) and KCl caused a dose dependent contraction in muscle cells enzymatically digested from cat gallbladder. Maximal contraction was obtained at concentration of $10^{-9}M$ for CCK-8, $10^{-5}M$ for ACh and 20mM for KCl. CCK-8 induced contraction was unaffected in calcium free physiological salt solution (PSS) and was completely blocked by strontium substitution for calcium (p<0.001). In contrast, KCl evoked contraction was blocked in calcium free PSS (p<0.01) but was unaffected by strontium replacement of calcium. The contraction elicited by ACh was only slightly reduced in calcium free PSS (p<0.05) and was unaltered by strontium. Muscle cells permeabilized with saponin contracted in response to inositol 1,4.5-trisphosphate $(IP_3)$ and CCK-8. The contraction was blocked by the calmodulin antagonist CGS 9343B (p<0.001), whereas heparin completely blocked the effect of $IP_3$ (p<0.001). The protein kinase C (PKC) antagonist H7 had no effect on either agonist. We conclude that CCK-8 induced gallbladder muscle contraction is mediated by $IP_3$ dependent intracellular calcium release from intracellular stores and a calmodulin dependent pathway; ACh may utilize both extracellular and intracellular calcium. KCl causes muscle contracrion through influx of extracellular calcium and a calmodulin independent machanism.

• The Korean Journal of Pharmacology
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• v.32 no.1
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• pp.51-56
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• 1996

The objectives of this study is to find out mechanism of vasodilating effects of ANP in 2K-1C renovascular hypertensive rat aorta and to compare with those of normotensive rat aorta. In 2K-1C renovascular hypertensive rat, average arterial blood pressure and plasma renin activity were higher than in normotensive rat. In 2K-1C renovascular hypertensive rat aorta, NE sensitivity was more increased and maximal contraction of aorta by NE was higher than those of normotensive rat aorta. ANP inhibited NE-induced contraction in both 2K-1C renovascular hypertensive and normotensive rat aorta, concentration-dependently. However, ANP was less effective for relaxing NE-induced contraction in 2K-1C renovascular hypertensive rat aorta than in normotensive rat aorta. ANP inhibited $^{45}Ca^{2+}$ uptake induced by NE in both 2K-1C renovascular hypertensive and normotensive rat aorta. From these results. inhibition of $Ca^{2+}$ influx may be one of the vasodilating mechanism of ANP in 2K-1C renovascular hypertensive rat aorta. Although the potency of ANP in relaxing NE-induced contractions was attenuated, the efficacy of ANP was not changed in 2K-1C renovascular hypertensive rat aorta compared with that of ANP in normotensive rat aorta. Abbreviations: ANP, Atrial natriuretic peptide; 2K-1C, 2-kidney 1 clip; NE, norepinephrine; SHR, Spontaneously hypertensive rat; DOC, Deoxycorticosterone; EDTA, Ethylenediaminetetra-acetic acid; PSS, Physiological salt solution; TRIS, tris(hydroxymethyl) aminomethane

• Journal of Chest Surgery
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• v.29 no.2
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• pp.191-198
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• 1996

Amrinone is a non-glycosidic, non-adrenergic positive inotropic agent with peripheral and coronary vasodilator effect. It inhibits phosphodiesterase F-III, the cardiac cyclic-AMP specific phosphodiesterase, selectively and potently. In this study, the effects of IV administered amrinone and dopamine were compared in 40 patients who had open heart surgery. Amrinone was administered as a bolus of 1 5~2mglkg for several minutes, followed by continuous infusion at 5~1 Oug/kg/min. The hemodynamic measurements including heart rate, systolic and diastolic pressure, cardiac index, pulmonary wedge pressure, and systemic vascular resistance were recorded immediately for 12~24 hours awl 7th day following operation. In amrinone group, cardiac index increased from 3.73$\pm$1.39 L/min/m2 to 5.44$\pm$2.65 L/min/m2 at the time of posterative 48 hours (n=20, p< 0.05). The decrease in systemic vascular resistance from 1237.5 $\pm$ 637.7 dyne/sec/cm2 to 1000.8 $\pm$ 608.5 dyne/sec/cm2(p<0.05). In Dopamine group, the heart rate increased from 92.1 $\pm$ 13.0/min to 101.0 $\pm$ 13.1/min and the cardiac index decreased from 3.40 $\pm$ 0.50 L/min/m2 to 2.53 $\pm$ 1.15 L/min/m2 at the time of postoperative 12 hours(p<0.05). Systemic vascular resistance increased from 1058.5 $\pm$ 234.6 dyne/sec/cm2 to 1979.7 $\pm$ 759.2 dynelsec/cm2 The comparison of the hemodynamic effects of amrinone and dopamine, both drugs improved cardiac performance. But the administration of amrinone results in a higher cardiac index, diastolic blood pressure and lower systemic vascular resistance than those achieved with dopamine (p<0.05). The uniqueness of the action of amrinone on the heart and its sustained hemodynamic effect suggest it has clinical promise, pos operative care of cardiac surgery

• Journal of Oral Medicine and Pain
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• v.38 no.1
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• pp.53-67
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• 2013

This study was aimed to evaluate the masticatory efficiency after botulinum toxin type A (BTX-A) injection during 12 weeks using objective and subjective test. Also, we compared the difference of masticatory efficiency between group that injected into the masseter muscle only (M-group) and group that injected into the masseter and temporalis muscle (M-T group). The mixing ability index (MAI) was used as the objective indicator, and visual analogue scale (VAS) and food intake ability (FIA) index were used as the subjective indicators. It was concluded that masticatory efficiency was significantly lowered after a BTX-A injection into the masticatory muscle, but it gradually recovered in a predictable pattern by the 12 weeks. The disturbance of subjective masticatory efficiency was lasted longer than objective masticatory efficiency. The masticatory efficiency was lower in M-T group than M group. It was statistically significant in the VAS and FIA at 4 weeks, but the MAI showed no significancy. After 4weeks, there was rapid recovery of muscle function in M-T group, and the difference between two groups was not significant. It could be concluded that there will be no serious disturbance of mastication compared to injection is done only into the masseter muscle, even if injection is done into the masseter and temporalis muscle in dose of this study. According to the food properties, it was confirmed that people feel more discomfort on taking hard and tough foods after BTX-A injection and not only hard foods, but also intake of soft and runny foods were influenced by botulinum toxin injection.