• Journal of The Korean Dental Society of Anesthesiology
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• v.13 no.4
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• pp.161-166
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• 2013

Dexmedetomidine is a potent alpha-2-adrenergic agonist, more selective than clonidine, with widespread actions on the mammalian brain. A large body of recent work supports its analgesia and sympatholytic properties. Dexmedetomidine is a useful medication with many clinical applications. The medication has shown efficacy in decreasing the need for opioids, benzodiazepines, propofol, and other sedative medications. Dexmedetomidine has been used effectively for sedation during invasive procedures and in the ICU. Short-term sedation has been shown to be safe in studies, although hypotension and bradycardia are the most significant side effects. Dexmedetomidine is emerging as an effective therapeutic agent in the management of a wide range of clinical conditions with an efficacious, safe profile.

• Molecules and Cells
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• v.39 no.7
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• pp.557-565
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• 2016

The paired immunoglobulin-like type 2 receptor (PILR) family consists of two functionally opposite members, inhibitory $PILR{\alpha}$ and activating $PILR{\beta}$ receptors. PILRs are widely expressed in various immune cells and interact with their ligands, especially CD99 expressed on activated T cells, to participate in immune responses. Here we investigated whether PILR-derived agonists inhibit ${\beta}1$ integrin activity as ligands for CD99. PILR-derived peptides as well as PILR-Fc fusion proteins prevented cell adhesion to fibronectin through the regulation of ${\beta}1$ integrin activity. Especially, PILRpep3, a representative 3-mer peptide covering the conserved motifs of the PILR extracellular domain, prevented the clustering and activation of ${\beta}1$ integrin by dephosphorylating FAK and vinculin, which are major components of focal adhesion. In addition, PILRpep3 inhibited transendothelial migration of monocytes as well as endothelial cell tube formation. Furthermore, upon intraperitoneal injection of PILRpep3 into mice with collagen-induced arthritis, the inflammatory response of rheumatoid arthritis was strongly suppressed. Taken together, these results suggest that PILR-derived agonist ligands may prevent the inflammatory reactions of rheumatoid arthritis by activating CD99.

• The Korean Journal of Physiology and Pharmacology
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• v.12 no.6
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• pp.315-321
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• 2008

Eugenol is widely used in dentistry to relieve pain. We have recently demonstrated voltage-gated $Na^+$ and $Ca^{2+}$ channels as molecular targets for its analgesic effects, and hypothesized that eugenol acts on $P2X_3$, another pain receptor expressed in trigeminal ganglion (TG), and tested the effects of eugenol by whole-cell patch clamp and $Ca^{2+}$ imaging techniques. In the present study, we investigated whether eugenol would modulate 5'-triphosphate (ATP)-induced currents in rat TG neurons and $P2X_3$-expressing human embryonic kidney (HEK) 293 cells. ATP-induced currents in TG neurons exhibited electrophysiological properties similar to those in HEK293 cells, and both ATP- and $\alpha$, $\beta$-meATP-induced currents in TG neurons were effectively blocked by TNP-ATP, suggesting that $P2X_3$ mediates the majority of ATP-induced currents in TG neurons. Eugenol inhibited ATP-induced currents in both capsaicin-sensitive and capsaicin-insensitive TG neurons with similar extent, and most ATP-responsive neurons were IB4-positive. Eugenol inhibited not only $Ca^{2+}$ transients evoked by $\alpha$, $\beta$-meATP, the selective $P2X_3$ agonist, in capsaicin-insensitive TG neurons, but also ATP-induced currents in $P2X_3$-expressing HEK293 cells without co-expression of transient receptor potential vanilloid 1 (TRPV1). We suggest, therefore, that eugenol inhibits $P2X_3$ currents in a TRPV1-independent manner, which contributes to its analgesic effect.

• Korean Journal of Veterinary Research
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• v.38 no.4
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• pp.712-719
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• 1998

Thyroid function is mainly regulated through cAMP and phophatidylinositol, and it is well known that TSH-stimulated thyroxine ($T_4$) release is inhibited by catecholamine from mouse thyroids via the ${\alpha}_1$-adrenoceptor stimulation. Previous study has established that the inhibition of $T_4$ release by ${\alpha}_1$-adrenoceptor stimulation results in activated protein kinase C (PKC). The purpose of this study was to determine if ion transport systems are involved in the inhibition of $T_4$ release elicited by ${\alpha}_1$-adrenergic agonist in mouse thyroids. TSH-, IBMX- and cAMP analogue-stimulated $T_4$ release were significantly inhibited by methoxamine, R59022 (diacylglycerol kinase inhibitor), and MDL (adenylate cyclase inhibitor). TSH-stimulated $T_4$ release could be inhibited by Bay K 8644 and cyclopiazoic acid, but not by verapamil and tetrodotoxin. The addition of nifedipine ($Ca^{2+}$ channel blocker), tetrodotoxin and lidocaine ($Na^+$ channel blockers), but not amiloride (EIPA) and ryanodine, completely blocked the inhibitory effects of methoxamine on $T_4$ release. TSH-stimulated $T_4$ release was also inhibited by benzamil ($Na^+-Ca^{2+}$ exchange inhibitor). TSH-, IBMX- and cAMP-stimulated $T_4$ release were inhibited by methoxamine or R59022, these effects were reversed by nifedipine. but not by verapamil. Furthermore, nifedipine reversed the inhibitory effects of benzamil and R59022 on TSH-stimulated $T_4$ release. These data suggest that the observed ${\alpha}_1$-adrenoceptor-mediated inhibition of $T_4$ release in mouse thyroids is the result of an increase in intracellular $Na^+$ or $Ca^{2+}$ effected via activation of fast $Na^+$ or nifedipine-sensitive $Ca^{2+}$ channels, and that $Na^+-Ca^{2+}$ exchange may play an important role in reducing thyroid hormone by increasing intracellular $Ca^{2+}$.

• Journal of the Korean Society of Food Science and Nutrition
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• v.34 no.9
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• pp.1336-1343
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• 2005

In the present study, we screened candidates for enhancing insulin action and secretion from Cinnamomum camphora (CC) fractions, in 3T3-L1 adipocytes and Min6 cells by investigating insulin- stimulated glucose uptake and glucose-stimulated insulin secretion, respectively. CC were extracted by $70\%$ ethanol followed by XAD-4 column chromatography with serial mixture solvents of methanol and water, and the fractional extractions were utilized for determining insulin action and secretion, and $\alpha$-glucoamylase suppressing activity, A significant insulin-stimulated glucose uptake was observed in 3T3-L1 adipocytes, giving 0.5 or $5{\mu}g/mL$ of $40\%\;and\;60\%$ methanol fractions plus 0.2 nM insulin, compared to the treatment of DMSO plus 0.2 nM insulin. The treatments of $40\%\;and\;60\%$ methanol fractions plus 0.2 nM insulin reached the glucose uptake of 10 nM insulin treatment. The $40\%$ methanol fraction increased triglyceride accumulation by stimulating differentiation and triglyceride synthesis similar to pioglitazone, PPAR-$\gamma$ agonist. No inhibition of $\alpha$-glucoamylase activity of CC fractions was observed. They did not modulate the insulin secretion capacity In either low or high glucose media. These results suggest that $40\%$ methanol fraction contains a potential insulin sensitizer to have a similar function of PPAR-$\gamma$ agonist. Crude CC extract may improve glucose utilization by enhancing insulin-stimulated glucose uptake without elevating glucose stimulated insulin secretion.

• Journal of Ginseng Research
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• v.21 no.2
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• pp.125-132
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• 1997

Our previous study showed that in vivo treatment of spontaneously hypertensive rats (SHR) with protopanaxatriol ginsenosides (PPT) reduces the blood pressure and inhibits the con- tractions induced by endothelium-derived contracting factor (prostaglandin endoperoxide ($PGH_2$) and superoxide anion) in aorta isolated from SHR. The aim of the present study is to examine whether PPT improves endothelial functions in the isolated thoracic aorta of SHR in vitro. Treatments of aortic rings with PPT, purified ginsenoside $Rg_1$ ($Rg_1$) or indomethacin normalized endotheliuln-dependent relaxation to acetylcholine, but not with protopanaxadiol ginsenosides (PPD) and purified ginsenoside Rb1 (Rb1). The effects of PPT were dose-dependent. PGH,- and oxygen free radical-inducted contractions in rat aorta without endothelium were inhibited by PPT or $Rg_1$, but not by PPD or $Rb_1$. Contractions induced by PGF2$\alpha$, U-46619, a stable thromboxane A2 agonist or KCI (60 mM) were not inhibited by PPT, $Rg_1$ or $Rb_1$. These findings demonstrate that PPT but not PPD scavenges the oxygen-derived free radicals and/or antagonize the effects of $PGH_2$ in the vascular smooth muscle and may explain the hypotensive effect of ginseng in the SHR.

• The Korean Journal of Physiology and Pharmacology
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• v.3 no.4
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• pp.383-391
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• 1999

This study was carried out to determine whether the effects of an ${\alpha}_2-adrenoceptor$ agonist, clonidine, on mean arterial pressure (MAP) and heart rate (HR) are influenced by mild hypothermia. Experiments were performed in respiration-controlled and spontaneously breathing pentobarbital-anesthetized rats. Rectal temperature was maintained at $37.5{\pm}0.3^{circ}C$ for normothermic groups or at $35.2{\pm}0.3^{circ}C$ for mild hypothermic groups. Intravenous injection of clonidine (1 and 2 ${\mu}g/kg)$ produced depressor and bradycardic responses in spontaneously breathing rats under both normothermic and mild hypothermic condition: a decrease in MAP was not altered but bradycardic response was significantly augmented in the mild hypothermic group as compared with the normothermic group. Under the respiration-controlled condition, the hypotensive effect of clonidine $(2\;{\mu}g/kg)$ was reduced, whereas the bradycardic effect was increased in mild hypothermic rats as compared with normothermic rats. Both hypotensive and bradycardic effects of clondine $(2\;{\mu}g/kg)$ were blocked by pretreatment with an ${\alpha}_2-adrenoceptor$ antagonist, yohimbine (0.5 mg/kg), in both thermal conditions. Yohimbine (0.5 mg/kg, i.v.) alone produced signifcantly an increase in heart rate in the mild hypothermic group than in the normothermic group. Pretreatment with a muscarinic receptor antagonist, atropine methylnitrate (1 mg/kg, i.v.), attenuated the bradycardic effect of clonidine in the mild hypothermic group but not in the normothermic group. These results suggest that clonidine- induced bradycardia is amplified by mild hypothermia probably through an increased parasympathetic activity.

• Korean Journal of Veterinary Research
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• v.56 no.2
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• pp.67-74
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• 2016

Tomato extract has been shown to exert antiplatelet activity in vitro and to change platelet function ex vivo, but with limitations. In this study, antiplatelet activity of water soluble tomato concentrate (Fruitflow I) and dry water soluble tomato concentrate (Fruitflow II) was investigated using rat platelets. Aggregation was induced by collagen and adenosine diphosphate and granule-secretion, $[Ca^{2+}]_i$, thromboxane B2, cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) levels were examined. The activation of integrin ${\alpha}_{IIb}{\beta}_3$ and phosphorylation of signaling molecules, including mitogen-activated protein kinase (MAPK) and PI3K/Akt, were investigated by flow cytometry and immunoblotting, respectively. Prothrombin time (PT) and activated partial thromboplastin time (aPTT) were examined. Moreover, in vivo thrombus weight was tested by an arteriovenous shunt model. Fruitflow I and Fruitflow II significantly inhibited agonist induced platelet aggregation, adenosine triphosphate and serotonin release, $[Ca^{2+}]_i$, and thromboxane B2 concentration, while having no effect on cAMP and cGMP levels. Integrin ${\alpha}_{IIb}{\beta}_3$ activation was also significantly decreased. Moreover, both concentrates reduced phosphorylation of MAPK pathway factors such as ERK, JNK, P38, and PI3K/Akt. In vivo thrombus formation was also inhibited. Taken together, these concentrates have the potential for ethnomedicinal applications to prevent cardiovascular ailments and can be used as functional foods.

• BMB Reports
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• v.43 no.5
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• pp.337-343
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• 2010

Fenofibrate, an agonist of $PPAR{\alpha}$, plays an important role in activating many proteins catalyzing lipid metabolism, and it also has a considerable effect on improvement of insulin sensitivity in the diabetic condition. To investigate fenofibrate-dependent expression of peripheral tissue proteins in diabetes, we analyzed whole muscle or fat proteins of fenofibrate-fed OLETF rats, an animal model of type II diabetes, using 2-dimensional gel electrophoresis. We found that many proteins were specifically expressed in a fenofibrate-dependent manner in these diabetic rats. In particular, a functionally unknown C11orf59 protein was differentially expressed in the muscle tissues (about 5-fold increase) in fenofibrate-fed OLETF rats as compared to control rats. Additionally, the signal proteins phosphatidylethanolamine binding protein and IkB interacting protein were differentially regulated in the fenofibrate-treated adipose tissues. We suggest here that these proteins might be involved in controlling lipid or carbohydrate metabolism in diabetes via $PPAR{\alpha}$ activation.

• BMB Reports
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• v.41 no.3
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• pp.223-229
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• 2008

Reactive oxygen species (ROS) are implicated in vascular homeostasis. This study investigated whether ${O_2}^{\cdot^-}$, the foundation molecule of all ROS, regulates vasomotor function. Hence, vascular reactivity was measured using rat thoracic aortas exposed to an ${O_2}^{\cdot^-}$ generator (pyrogallol) which dose-dependently regulated both $\alpha$-adrenergic agonist-mediated contractility to phenylephrine and endothelium-dependent relaxations to acetylcholine. Pyrogallol improved and attenuated responses to acetylcholine at its lower (10 nM - 1 ${\mu}M$) and higher (10 - 100 ${\mu}M$) concentrations, respectively while producing the inverse effects with phenylephrine. The endothelial inactivation by L-NAME abolished acetylcholine-induced vasodilatations but increased phenylephrine and KCl-induced vasoconstrictions regardless of the pyrogallol dose used. Relaxant responses to sodium nitroprusside, a nitric oxide donor, were not affected by pyrogallol. Other ROS i.e. peroxynitrite and $H_2O_2$ that may be produced during experiments did not alter vascular functions. These findings suggest that the nature of ${O_2}^{\cdot^-}$-evoked vascular function is determined by its local concentration and the presence of a functional endothelium.