• 약학회지
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• 제54권5호
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• pp.392-397
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• 2010

The aim of present study was to investigate the possible influence and related mechanism of additional alcohol on the flavonoid- induced arterial relaxation. Agonist-induced vascular smooth muscle contractions involve the activation of thick or thin filament pathway. However, there are no reports addressing the question whether this pathway is involved in quercetin-induced relaxation cotreated with alcohol in rat aortae contracted with phorbol ester, fluoride or thromboxane $A_2$ mimetic U-46619. We hypothesized that cotreated alcohol plays a role in vascular relaxation evoked by quercetin in rat aortae. Endothelium-denuded arterial rings from male Sprague-Dawley rats were used and isometric contractions were recorded using a computerized data acquisition system. Quercetin inhibited phorbol ester, fluoride or thromboxane $A_2$-induced contraction regardless of endothelial function. However, alcohol didn't decrease any agonist-induced contraction. Interestingly, only in thromboxane $A_2$-induced contraction, synergistic results were observed in aortae denuded and cotreated with quercetin and alcohol suggesting that additional pathways different from antioxidation or endothelial nitric oxide synthesis might be involved in the vasorelaxation. In conclusion, in the agonists-contracted rat aortae, quercetin and alcohol together showed synergistic response regardless of endothelial function in an agonist-dependent manner.

• Molecules and Cells
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• 제27권2호
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• pp.191-198
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• 2009

The present study was undertaken to determine whether treatment with genistein, the plant-derived estrogen-like compound influences agonist-induced vascular smooth muscle contraction and, if so, to investigate related mechanisms. The measurement of isometric contractions using a computerized data acquisition system was combined with molecular experiments. Genistein completely inhibited KCl-, phorbol ester-, phenylephrine-, fluoride- and thromboxane $A_2$-induced contractions. An inactive analogue, daidzein, completely inhibited only fluoride-induced contraction regardless of endothelial function, suggesting some difference between the mechanisms of RhoA/Rho-kinase activators such as fluoride and thromboxane $A_2$. Furthermore, genistein and daidzein each significantly decreased phosphorylation of MYPT1 at Thr855 had been induced by a thromboxane $A_2$ mimetic. Interestingly, iberiotoxin, a blocker of large-conductance calcium-activated potassium channels, did not inhibit the relaxation response to genistein or daidzein in denuded aortic rings precontracted with fluoride. In conclusion, genistein or daidzein elicit similar relaxing responses in fluoride-induced contractions, regardless of tyrosine kinase inhibition or endothelial function, and the relaxation caused by genistein or daidzein was not antagonized by large conductance $K_{Ca}$-channel inhibitors in the denuded muscle. This suggests that the RhoA/Rho-kinase pathway rather than $K^+$- channels are involved in the genistein-induced vasodilation. In addition, based on molecular and physiological results, only one vasoconstrictor fluoride seems to be a full RhoA/Rho-kinase activator; the others are partial activators.

• The Korean Journal of Physiology and Pharmacology
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• 제5권1호
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• pp.87-92
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• 2001

Carbon monoxide (CO) binds to soluble guanylate cyclase to lead its activation and elicits smooth muscle relaxation. The vascular tissues have a high capacity to produce CO, since heme oxygenase-2 (HO-2) is constitutively expressed in endothelial and smooth muscle cells, and HO-1 can be greatly up-regulated by oxidative stress. Moreover, the substrate of HO, heme, is readily available for catalysis in vascular tissue. Although the activation of heme oxygenase pathway under various stress conditions may provide a defence mechanism in compromised tissues, the specific role of HO-1-derived CO in the control of aortic contractility still remains to be elucidated. The present study was done to determine the effect of HO-1 induction on the aortic contractility. Thus, the effects of incubation of aortic tissue with S-nitroso-N-acetylpenicillamine (SNAP) for 1 hr on the aortic contractile response to phenylephrine were studied. The preincubation with SNAP resulted in depression of the vasoconstrictor response to phenylephrine. This effect was restored by HO inhibitor or methylene blue but not by NOS inhibitor. The attenuation of vascular reactivity by preincubation with SNAP was also revealed in endothelium-free rings. $AlF4^--evoked$ contraction in control did not differ from that in SNP-treated group. These results suggest that increased production of CO was responsible for the reduction of the contractile response to phenylephrine in aortic ring preincubated with SNAP and this effect of SNAP was independent on endothelium.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1998년도 Proceedings of UNESCO-internetwork Cooperative Regional Seminar and Workshop on Bioassay Guided Isolation of Bioactive Substances from Natural Products and Microbial Products
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• pp.176-176
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• 1998

An enhanced formation of nitric oxide (NO) is an important mediator of hypotention, peripheral vasodilation and vascular hyporeactivity to vasoconstrictor agents in endotoxaemia. And tumor necrosis factor (TNF${\alpha}$), as a primary mediator of circulatory shock has been known to induce inducible nitric oxide synthase (i-NOS), leading to excessive production of NO. We isolated two sesquiterpene lactone compounds from Saussurea lappa and their structures were elucidated as dehydrocostus lactone and costunolide. These compounds inhibit the production of both NO and TNF${\alpha}$ by LPS (1 $\mu\textrm{g}$/$m\ell$)-activated Raw 264.7 cells. NO was measured spectropho-tometrically as nitrite by the Griess reagent and TNF${\alpha}$ by ELISA. Dehydrocostus lactone (IC$\sub$50/ : 3.0 ${\mu}$M) and costunolide (IC$\sub$50/ : 4.5 ${\mu}$M) inhibited the production of NO in LPS-activated Raw 264.7 cells by suppressing inducible nitric oxide synthase enzyme expression. These compounds also decreased the TNF${\alpha}$ levels in LPS-activated system in vitro and in vivo.

• Molecular Medicine Reports
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• 제19권5호
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• pp.3767-3774
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• 2019

The contractility of vascular smooth muscle cells (VSMCs) controls the lumen diameter of vessels, thus serving a role in regulating blood pressure and organ blood flow. Although arginases are known to have numerous effects in the biological activities of VSMCs, the effects of arginase II on the constriction of VSMCs has not yet been investigated. When conducting a natural products screen for an inhibitor against arginase, the present study identified that a relatively high concentration of resveratrol (RSV) exhibited arginase inhibitory activity. Therefore, the present study investigated whether RSV could regulate VSMCs contractions and the underlying mechanism. Arginase inhibition by RSV led to an increase in the concentration of the substrate L-Arg and an accompanying increase in the cytosol Ca2+ concentration [(Ca2+)c] in VSMCs. The increased [Ca2+]c induced by RSV and L-Arg treatments resulted in CaMKII-dependent MLC20 phosphorylation. The effects of RSV on VSMCs were maintained even when VSMCs were pre-treated with sirtinol, an inhibitor of Sirt proteins. In a vascular tension assay with de-endothelialized aortic vessels, vasoconstrictor responses, which were measured using phenylephrine (PE), were significantly enhanced in the RSV- and L-Arg-treated vessels. Therefore, although arginase inhibition has exhibited beneficial effects in various diseases, care is required when considering administration of an arginase inhibitor to patients with vessels endothelial dysfunction as RSV can induce vessel contraction.

• Journal of Korean Biological Nursing Science
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• 제22권4호
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• pp.249-259
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• 2020

Purpose: Carbapenemase-producing Enterobacteriaceae (CPE) are associated with considerable mortality. This study was aimed to identify survival factors among medical care unit patients with CPE. Methods: We conducted a retrospective cohort; data were collected from September 2017 to June 2019 through electronic medical records. The data collected were general characteristics, disease-related characteristics, severity-related characteristics, and treatment-related characteristics. Data were analyzed based on frequency, mean, standard deviation, Chi-square test, Fisher's exact test, t-test, Pearson's correlation coefficient, and Cox proportional hazard model using SPSS/WIN 21.0 program. Results: Seventy-seven patients were included (59 survivors and 18 deceased) in the study. Univariate analysis identified factors for survival associated with acquired CPE as age (t= -1.56, p= .037), simplified acute physiology 3 (SAPS3) score of admission date (t= -2.85, p= .006), Glasgow coma scale (GCS) of CPE acquisition date (t= 2.38, p= .020), artery catheter at CPE acquisition date (χ²= 4.58, p= .032), vasoconstrictor agents use at CPE acquisition date (χ²= 6.81, p= .009), platelet at CPE acquisition date (t= 2.27, p= .025), lymphocyte at CPE acquisition date (t= 2.01, p= .048), calcium at CPE acquisition date (t= 2.68, p= .009), albumin at CPE acquisition date (t= 2.29, p= .025), and creatinine at CPE acquisition date (t= 2.24, p= .028). Multivariate Cox proportional hazard model showed that GCS at CPE acquisition date (HR= 1.14, 95% CI= 1.05-1.22), lymphocyte at CPE acquisition date (HR= 1.05, 95% CI= 1.00-1.10), and creatinine at CPE acquisition date (HR= 1.25, 95% CI= 1.04-1.49) were independent survival factors among medical intensive care unit patients with CPE. Conclusion: Based on the study results, it is necessary to develop nursing interventions that can aid in the management of patients with CPE and identify their effects.

• Maxillofacial Plastic and Reconstructive Surgery
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• 제27권3호
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• pp.276-282
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• 2005

Inferior alveolar nerve block using lidocaine is the most frequent local anesthetic method in the dental treatment, but clinically it is not always successful. The 2% lidocaine cartridge has been used commonly in dental anesthesia. It contains vasoconstrictor and antioxidant, which presents low pH which provides chemical stability and longer shelf life. But alkalinized local anesthetics has less tissue trauma, easier dissociation of the non-ionized base which penetrates nerve sheath, rapid onset and more intensity. In this study, in inferior alveolar nerve block, alkalinized lidocaine using sodium bicarbonate (experimental group) is compared with plain lidocaine (control group) about injection pain, anesthetic onset, duration and postinjection discomfort. In inferior alveolar nerve block, alkalinized lidocaine using sodium bicarbonate showed lower injection pain. There was significant difference statistically from plain lidocaine(p=0.019). Comparing with plain lidocaine, alkalinized lidocaine produced more rapid onset (lip & pulp anesthetic onset), there was no significant difference(p>0.05). but there was boundary significance (0.050.05). These results suggest that addition of sodium bicarbonate to 2% lidocaine(1:100,000 epinephrine) for inferior alveolar nerve block is more effective for reduction of injection pain and onset time.

• BMB Reports
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• 제42권4호
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• pp.200-205
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• 2009

Thromboxane A2 (TBXA2) is a potent vasoconstrictor in cerebral circulation and is a known contributor to the pathogenesis of cerebral infarction. Thromboxane A2 synthase 1 (TBXAS1) and thromboxane A2 receptors (TBXA2R) are key components in TBXA2 function. We examined whether genetic variants in TBXA2R and TBXAS1 are risk factors for cerebral infarction by genotyping 453 Korean patients with noncardiogenic cerebral infarction and 260 controls. A few, specific polymorphisms in the TBXA2R (-3372G>C, +4710T>C and 4839T>C) and TBXAS1 (+16184G>T, +141931A>T and +177729G>A) genes were chosen and investigated. Logistic regression showed the frequencies of TBXAS1+16184G>T and TBXAS1-ht3 were significantly more frequent in cerebral infarction (P = 0.002, OR = 2.75 and P = 0.01, OR = 1.57, respectively), specifically in small-artery occlusion (SAO) type of cerebral infarction (P = 0.0003 and 0.005, respectively). These results suggest specific TBXAS1 gene polymorphisms may be a useful marker for development of cerebral infarction, especially SAO type in Korean population.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1994년도 춘계학술대회 and 제3회 신약개발 연구발표회
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• pp.287-287
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• 1994

In the present study, it was aimed to asses the possibility that calcitonin gene-related peptide (CGRP) released in response to transient hypotension may contribute to the reflex autoregulation of cerebral blood flow as a putative modulator. Changes in pial arterial diameter (mean, 33.0 ${\pm}$ 1.1 $\mu\textrm{m}$) with changes in systemic arterial blood pressure (mean, 101.9 ${\pm}$ 2.7 mmHg) were observed directly through a closed cranial window in anesthetized normotensive rats. Image of the pial vessels was captured with a stereoscope connected to a CCD video camera and the diameter was measured with a microscaler. In the capsaicin-treated rats (one day prior to experiment, 50 nmol capsaicin injected intracisternally), both vasodilater and vasoconstrictor responses evoked by a transient hypotension and the reverse of blood pressure were markedly attenuated or almost abolished. When changes in pial arterial diameter were plotted as a function of changes in blood pressure, the slopes of both regression lines (for vasodilators and vasoconstrictors ) were markedly reduced. Similar reductions were evidenced under treatment wi th the CGRP antibody serum (1:1,000) and following CGRP receptor desensitization. However, the autoregulatory mechanics were neither affected by treatment wi th spantide (1 ${\mu}$M), substance P antagonist, nor by substance P receptor desensitization. Suffusion wi th mock cerebrospinal fluid containing CGRP and cromakalim caused a vasodilatation in a concentration-dependent manner, respectively and their effects were antagonized by glibenclamide. Substance P produced a vasodilatation, which was, however, little affected by glibenclamide. These observations indicate that the CGRP released from the perivascular sensory fibers in response to a hypotension is implicated in the modulation of the autoregulation of cerebral blood flow.

• The Korean Journal of Physiology and Pharmacology
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• 제1권5호
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• pp.581-589
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• 1997

This study was undertaken to examine the effects of ultraviolet light (UVL) and rebamipide on the cutaneous blood flow and tissue survival on rabbit skin flap. In a random bipedicle flap, Laser Doppler Flowmetry (LDF) was employed to measure the blood flow of flap (BFF). Wound Margin Strength (WMS) measured by force transducer and Light microscophy were used for evaluation of tissue viability. Single exposure to UVL increased the BFF gradually for more than 15 hours, and decreased the vasoconstrictor effect of intravenous phenylephrine. The UVL-induced increase in BFF regressed after 18 hours of irradiation, and this regression was tended to be enhanced by intradermal injection of L-NAME, a nitric oxide synthase (NOS) inhibitor, but the regression was significantly reversed by acetylcholine, an endothelial constitutive NOS (cNOS) activator and L-arginine, an NO precusor. Rebamipide, a novel antiulcer agent known to scavenge the hydroxyl radical, abruptly reversed the spontaneous regression of the UVL- induced increase in BFF by the same manner as L-arginine. In ischemic skin flap, rebamipide increased the BFF abruptly by the same manner as sodium nitroprusside (SNP), an NO doner, while N-acetylcystein (NAC), a free radical scavenger, gradually increase the BFF. The rebamipide-induced increase in BFF was sustained at the level of the SNP-induced increase in BFF during the late period of experiment. Rebamipide increased the WMS of skin flaps and prevented the tissue necrosis in comparison with L-NAME. Based on these results, it is concluded that in rabbit skin, UVL irradiation increases the BFF by NO release, and rebamipide exerts a protective effect on the viability of ischemic skin flaps by either or both the increase in BFF by NO release and free radical scavenger effect.