• The Korean Journal of Physiology and Pharmacology
• /
• v.25 no.5
• /
• pp.449-457
• /
• 2021

The sleep-wake cycle is regulated by the alternating activity of sleep- and wake-promoting neurons. The dorsal raphe nucleus (DRN) secretes 5-hydroxytryptamine (5-HT, serotonin), promoting wakefulness. Melatonin secreted from the pineal gland also promotes wakefulness in rats. Our laboratory recently demonstrated that daily changes in nitric oxide (NO) production regulates a signaling pathway involving with-no-lysine kinase (WNK), Ste20-related proline alanine rich kinase (SPAK)/oxidative stress response kinase 1 (OSR1), and cation-chloride co-transporters (CCC) in rat DRN serotonergic neurons. This study was designed to investigate the effect of melatonin on NO-regulated WNK-SPAK/OSR1-CCC signaling in wake-inducing DRN neurons to elucidate the mechanism underlying melatonin's wake-promoting actions in rats. Ex vivo treatment of DRN slices with melatonin suppressed neuronal nitric oxide synthase (nNOS) expression and increased WNK4 expression without altering WNK1, 2, or 3. Melatonin increased phosphorylation of OSR1 and the expression of sodium-potassium-chloride co-transporter 1 (NKCC1), while potassium-chloride co-transporter 2 (KCC2) remained unchanged. Melatonin increased the expression of tryptophan hydroxylase 2 (TPH2, serotonin-synthesizing enzyme). The present study suggests that melatonin may promote its wakefulness by modulating NO-regulated WNK-SPAK/OSR1-KNCC1 signaling in rat DRN serotonergic neurons.

• Journal of Chest Surgery
• /
• v.41 no.5
• /
• pp.541-549
• /
• 2008

Background: Vasoconstrictor-induced reduction in arterial graft diameter can cause significant flow deprivation. The aim of this study was to evaluate the effect of vasodilator pretreatment on vasoconstrictor-induced blood vessel spasm in vitro. Material and Method: Rabbit brachial arteries (BA) and celiac arteries (CA) were cut into rings $(3{\sim}4mm)$ and suspended with a force displacement transducer (TSD $125C^{(R)}$, Biopac Inc. USA) in a tissue bath filled with 5 mL modified Krebs solution bubbled with 5% $CO_2$ and 95% $O_2\;at\;38^{\circ}C$. The rings were contracted with vasoconstrictors, and the developed tension changes were considered control values. The rings were then pre- treated with $30{\mu}M$ nitroglycerin, nicardipine, verapamil, and papaverine, respectively, for 40 minutes and rinsed with the physiologic buffered salt solution three times every 15 min. The vasoconstrictor-induced tension changes after the previous procedure were considered experimental values. Data are expressed as the percentage tension induced by vasoconstrictors before and after pretreatment with vasodilators. Result: Nicardipine depressed vasoconstriction induced by norepinephrine, angiotensin II (All), and U46619 in both the BA and the CA more significantly than did nitroglycerin (p<0.01) and verapamil (p<0.05). Verapamil depressed vasoconstriction induced by 5-hydroxytryptamine (5HT), All, and U46619 in the BA and by 5HT in the CA more significantly than did nitroglycerin (p<0.01). Conclusion: These findings suggest that both nicardipine and verapamil effectively depressed vasoconstrictor action. Nicardipine is thought to be more effective than verapamil for the prevention of vasoconstrictor action.

• The Korean Journal of Pharmacology
• /
• v.31 no.2
• /
• pp.179-194
• /
• 1995

This study aimed to determine whether exposure to stress during developmental period causes permanent behavioral and/or neurochemical alterations. Alterations of behavior were studied in young and aged rats which have been exposed to uncontrollable and unpredictable electric shocks on postnatal day(PND) 14 or PND 14 and 21. The concentrations of monoaminergic neurotransmitters were also measured to determine whether the behavioral alterations were accompanied by neurochemical changes. The results obtained are as follows: 1) The rate of increase in body weight was reduced at one day after exposure to the 1st series of shocks on PND14. However, these findings could not be observed after exposure to the 2nd series of shocks on PND 21. 2) Explorative activity decreased at one day after exposure to the 1st series of shocks on PND14. However this findings could not be observed after exposure to the 2nd series of shocks on PND 21. 3) At 100 days of age, there were little changes in the spontaneous locomotor activities measured for consecutive 23 hrs. However, there was positive correlation between the shock number showing the 1st helplessness during receiving the 1st series of shocks and the night time ambulatory activity of females, and was negative correlation between the shock number showing the 1st helplessness during receiving the 1st or 2nd series of shocks on PND 14 or 21 and the night time ambulatory activity of females. 4) At $360{\sim}390$ days of age, night time ambulatory activity decreased in female rats which have been exposed to shocks on PND 14 and 21, but not in males. 5) In the aged female rats, the concentrations of 5-HT, dopamine and their metabolites were not different among groups. However, the ratio of 5-HIAA/5-HT increased in the frontal cortices of rats exposed to shocks on PND 14 and 21. These results demonstrate that the early experience of serious stress results in persistent alterations of behavior accompanying altered neurochemistry, and aging may unmask a subtle neuronal deficit causes by the early experience of serious stress.

• Journal of Chest Surgery
• /
• v.31 no.9
• /
• pp.884-892
• /
• 1998

Background: The gastroepiploic artery is not only an alternative graft but also may be considered an important primary graft for coronary revascularization. However, the long-term patency of the gastroepiploic arterial graft is yet to be determined and the incidence of perioperative spasm and long-term patency of a coronary graft may be affected by the properties of the graft response to certain vasoactive substances. The reactivity of the gastroepiploic artery to vasoactive substances has not been studied extensively and the results of the studies are contradictory. Material and Method: This study was designed to test the reactivity of human gastroepiploic artery to four constrictors and four relaxants. The middle sections of the human gastroepiploic arteries were collected from the patients undergoing gastrectomy and the arterial rings with intact endothelium were suspended in organ baths for isometric tension recording. Result: Epinephrine, norepinephrine, and potassium chloride induced the maximum constriction to higher forces (7.0$\pm$1.1g, 6.6$\pm$0.9g, and 6.5$\pm$1.1g) than 5-hydroxytryptamine did (3.8$\pm$1.7g, p<0.05). Nitroprusside and histamine induced almost full relaxation in the gastroepiploic arteries preconstricted with norepinephrine. There was no significant difference between two relaxants regarding maximum relaxation force. Acetylcholine induced the maximum relaxation to weaker force when compared with nitroprusside and histamine (p<0.05), and isoproterenol was the weakest of the relaxants (p<0.05 compared with acetylcholine). Conclusion: The gastroepiploic artery has a strong capacity of endothelium-dependent relaxation which could have an important influence on long-term patency. The gastroepiploic artery exhibits a potent contractility to catecholamines and the enhanced contractility may facilitate vasospasm in the presence of high circulating levels of catecholamines. Nitroprusside, a potent relaxant in gastroepiploic artery, might be beneficial for the treatment of gastroepiploic arterial graft spasm. The gastroepiploic arterial graft with intact endothelium may respond weakly to beta-adrenoceptor agonist and 5-hydroxytryptamine.

• The Journal of Korean Physical Therapy
• /
• v.21 no.2
• /
• pp.109-116
• /
• 2009

Purpose: $17\beta$-estradiol is the most active endogenous estrogen, which is related to favorable changes in the plasma lipid profile, to relaxation of the coronary vessels, and to a decrease in platelet aggregation and vascular smooth muscle cell migration. However, although the beneficial effect of estrogens on plasma lipoproteins (ie, lowering low-density lipoprotein and increasing high-density lipoprotein cholesterol) contributes to cardiovascular protection, it does not fully account for the protective effect, particularly in the application of physical therapy, including low frequency electrical stimulation. Methods: The aim of this study was to demonstrate the inhibition of stressors, such as endothelin-1 (ET-1), serotonin (5-hydroxytryptamine, 5-HT), prostaglandin $F2\alpha$ ($PGF2\alpha$), and a protein kinase C (PKC) activator 12-deoxyphorbol 13-isobutyrate (DPB), induced isometric tension by $17\beta$-estradiol in vascular smooth muscle strips, respectively. In addition, the effects of low frequency electrical stimulation at the meridian points (CV-3, -4, Ki-12, SP-6, LR-3, BL-25, -28, -32, -52) on the indirect antihypertensive effect were examined by monitoring the changes in the serum $17\beta$-estradiol concentration in healthy volunteers. Results: Isometric tension analysis showed that the responses of inhibited tension by $17\beta$-estradiol were similar to the same stressors in rat aortic smooth muscle strips. Furthermore, although the continued amplitude modulation (AM) type of electrical stimulation was not increased significantly by electrical stimulation, the current of the frequency modulation (FM) type of low frequency electrical stimulation increased the serum $17\beta$-estradiol concentration in normal volunteers. Conclusion: These results, in part, suggest that $17\beta$-estradiol has the capacity to supress stressor-induced muscle tension, and electrical stimulation, particularly current of the FM type, has a modulatory effect on the sex steroid hormones, particularly $17\beta$-estradiol, in healthy volunteers.

• Science of Emotion and Sensibility
• /
• v.10 no.2
• /
• pp.243-252
• /
• 2007

Anti-depressant and anti-anxiety effects of Saccharomyces cerevisiae extract and its hydrolyzed fraction. The purpose of the present study was to examine the effect of Saccharomyces cerevisiae extract (SCE) and its hydrolyzed fraction (SCE-40) on depression and anxiety-related behaviors in mice. Actions of SCE and SCE-40 on serotonin, norepinephrine and GABAergic systems in the rat cerebral cortex membranes were also examined. SCE and SCE-40 significantly reduced the immobility time in the forced swimming and tail suspension test in mice. Duration time of the open arms in the elevated plus maze test was significantly increased in the SCE and SCE-40-treated groups, compared with the saline-treated control group. SCE and its fraction SCE-40 significantly inhibited serotonin and norepinephrine transporter and GABA receptor binding, compared to the saline-treated group. In addition, serotonin and norepinephrine reuptake were significantly suppressed by SCE and SCE-40. These results demonstrate that SCE and SCE-40 produce anti-depressant and anti-anxiety effects through enhancing central serotonin, norepinephrine and GABAergic transmissions. These results suggest that SCE and SCE-40 as functional food might prove to be an effective antidepressant and anti-anxiety agent.

• Journal of Pharmaceutical Investigation
• /
• v.30 no.3
• /
• pp.213-218
• /
• 2000

Ondansetron is a potent, highly selective 5-hydroxytryptamine3(5-HT3) receptor- antagonist, for the management of nausea and vomiting induced by cytotoxic chemotherapy and radiography, and the treatment of post-operative nausea and vomiting. The purpose of the present study was to evaluate the bioequivalence of two ondansetron tablets, $Zofran^{TM}$, (Glaxo Wellcome Korea Ltd.) and Hana ondansetron (Hana Pharmaceutical Co., Ltd.), according to the guidelines of Korea Food and Drug Administration (KFDA). Eighteen normal male volunteers, $23.56{\pm}1.79$ year in age and $67.35{\pm}8.35\;kg$ in body weight, were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After one tablet containing 8 mg of ondansetron was orally administered, blood was taken at predetermined time intervals and the concentrations of ondansetron in serum were determined using HPLC with UV detector. Pharmacokinetic parameters such as $AUC_t,\;C_{max}\;and\;T_{max}$ were calculated and ANOVA test was utilized for the statistical analysis of the parameters. The results showed that the differences in $AUC_t,\;C_{max}\;and\;T_{max}$ between two tablets were 7.53%, -0.23% and -3.92%, respectively when calculated against the $Zofran^{TM}$, tablet. The powers $(1-{\beta})$ for $AUC_t,\;C_{max}\;and\;T_{max}$ were above 99.00%, above 99.00% and 84.99%, respectively. Minimum detectable differences $(\Delta)\;at\;{\alpha}=0.1\;and\;1-{\beta}=0.8$ were all less than 20% (e.g., 12.25%, 10.88% and 18.37% for $AUC_t,\;C_{max}\;and\;T_{max}$, respectively). The 90% confidence intervals were all within ${\pm}20%$ (e.g., $-0.70{\sim}15.76,\;-7.53{\sim}7.08\;and\;-16.27{\sim}8.42\;for\;AUC_t,\;C_{max}\;and\;T_{max}$, respectively). All of the above parameters met the criteria of KFDA for bioequivalence, indicating that Hana ondansetron tablet is bioequivalent to $Zofran^{TM}$, tablet.

• Journal of the Korean Society of Food Science and Nutrition
• /
• v.32 no.5
• /
• pp.733-738
• /
• 2003

Chemical compositions and DPPH radical scavenger activity in different sections of safflower (Carthamus tinctorious L.) were investigated. Protein contained 28.39% in sprout and fat contained 20.47% in seed, respectively. Linoleic acid as predominant unsaturated fatty acid of safflower contained 80.01% in sprout and 78.27% in seed. Glucose contained 1253.6mg% in sprout and fructose contained 970.7mg% in sprout. Sucrose contained 912.0mg% in flower bud. Succinic acid was included 2795.3 mg% in flower, malic acid was included 2054.8mg% in leaf. K as minerals contained 2826.8mg% in leaf and 2613,6 mg% in sprout, Ca contained 1999.8mg% in leaf and 1160.9mg% in sprout. Total phenolics contained 5.8%, 4.7%, 4.4% in flower, sprout and leaf, and total flavonoid contained 6.5%, 2.5%, 2.0% in flower, sprout and leaf, respectively Serotonin-I (Ν- [2- (5-hydroxy - l Η- indol -3- yl)ethyl] ferulamide) as serotonin compounds was determined 147.7mg% in seed, serotonin - II (Ν-［2-(5-hydroxy-lΗ-indo-1-3yl )ethyl]-p-coumaramide) was determined 155.4 mg% in seed. Acacetin as flavonoid compounds was contained 116.5mg% in seed. Luteolin as flavonoid compounds was identified 388.3mg% in sprout, luteolin 7-glucoside was determined 692.3mg% in leaf, respectively. DPPH radical scavenger activity was measured by DPPH method, it was shown higher 114.2% in ethanol extract of flower and 113.6% in ethanol extract of leaf than 88.05% of 100 ppm BHA as chemical antioxidant.

• Tuberculosis and Respiratory Diseases
• /
• v.40 no.2
• /
• pp.135-146
• /
• 1993

Background: In acute pulmonary embolism it has been postulated that the constriction of bronchi and pulmonary artery secondary to neurohumoral response plays an important role in cardiopulmonary dysfunction in addition to the mechanical obstruction of pulmonary artery. Serotonin is considered as the most important mediator. Positive end expiratory pressure (PEEP) stimulates $PGI_2$ secretion from the vascular endothelium, but its role in acute pulmonary embolism is still in controversy. Methods: To study the cardiopulmonary effect and therapeutic role of Ketanserin, selective antagonist of 5-HT2 receptor, and PEEP in acute pulmonary embolism experimental acute pulmonary embolism was induced in dogs with autologous blood clot. The experimental animals were divided into 3 groups, that is control group, Ketanserin injection group and PEEP application group. Results: Thirty minutes after embolization, mean pulmonary arterial pressure and pulmonary vascular resistance increased and cardiac output decreased. $PaO_2,\;P\bar{v}O_2$ and oxygen transport decreased and physiological shunt and $PaCO_2$ increased. After injection of Ketanserin, comparing with control group, mean pulmonary arterial pressure, pulmonary vascular resistance and physiological shunt decreased, while cardiac output, $PaO_2$ and oxygen transport increased. All these changes sustained till 4 hours after embolization. After PEEP application pulmonary vascular resistance, $PaO_2$ and $PaCO_2$ increased, while physiological shunt, cardiac output and oxygen transport decreased. After discontinuation of PEEP, mean pulmonary arterial pressure and pulmonary vascular resistance decreased and were lower than control group, while $PaO_2$ and cardiac output increased and higher than control group. $PaCO_2$ decreased but showed no significant difference comparing with control group. Conclusion: It can be concluded that Ketanserin is effective for the treatment of acute pulmonary embolism. With PEEP hemodynamic status deteriorated, but improved better than control group after discontinuation of PEEP. Thus PEEP may be applied carefully for short period in acute pulmonary embolism if the hemodynamic status is tolerable.

• The korean journal of orthodontics
• /
• v.37 no.3 s.122
• /
• pp.171-181
• /
• 2007

Objective: The present study was aimed at an analytical formulation of the micro-implant related torque as a function of implant size, i.e. the diameter and length, screw size, and the bony resistance at the implant to bone interface. Methods: The resistance at the implant to cancellous bone interface $(S_{can})$ was assumed to be in the range of 1.0-2.5 MPa. Micro-implant model of Absoanchor (Dentos Inc. Daegu, Korea) was used in the course of the analysis. Results: The results showed that the torque was a strong function of diameter, length, and the screw height. As the diameter increased and as the screw size decreased, the torque index decreased. However the strength index was a different function of the implant and bone factors. The whole Absoanchor implant models were within the safe region when the resistance at the implant/cancellous bone $(=S_{can})$ was 1.0 or less. Conclusion: For bone with $S_{can}$ of 1.5 MPa, the cervical diameter should be greater than 1.5 mm if micro-implant models of 12 mm long are to be placed. For $S_{can}$ of 2.0 MPa, micro-implant models of larger cervical diameter than 1.5 mm were found to be safe only if the endosseous length was less than 8 mm.