• Toxicological Research
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• v.20 no.2
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• pp.89-100
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• 2004

The comet assay (also called the single-cell gel electrophoresis assay) has been widely used for detecting DNA damage and repair in individual cells. Since the conventional methods of evaluating comet assay data using frequency statistics are unsatisfactory we developed a new quantitative measure of DNA damage/repair that is based on all information residing in the dose/time-response curves of a comet experiment. Blood samples were taken from 25 breast cancer patients before undergoing radiotherapy. The comet assay was performed under alkaline conditions using isolated lymphocytes. Tail DNA, tail length, tail moment and tail inertia of the comet were measured for each patient at four doses of $\gamma$-rays (0, 2, 4 and 8 Gy) and at four time points after irradiation (0, 10, 20 and 30 min) using 100 cells each. The resulting three-dimensional dose-time response surface was modeled by multiple regression, and the second derivative, termed 2D, on dose and time was determined. A software module was programmed in SAS/AF to compute 2D values. We applied the new method successfully to data obtained from cancer patients to be assessed for their radiation sensitivity. We computed the 2D values for the four damage measures, i.e., tail moment, tail length, tail DNA and tail inertia, and examined the pairwise correlation coefficients of 2D both on the log scale and the unlogged scale. 2D values based on tail moment and tail DNA showed a high correlation and, therefore, these two damage measures can be used interchangeably as far as DNA repair is concerned. 2D values based on tail inertia have a correlation profile different from the other 2D values which may reflect different facets of DNA damage/repair. Using the dose-time response surface, other statistical models, e.g., the proportional hazards model, become applicable for data analysis. The 2D approach can be applied to all DNA repair measures, Le., tail moment, tail length, tail DNA and tail inertia, and appears to be superior to conventional evaluation methods as it integrates all data of the dose/time-response curves of a comet assay.

• The Korean Journal of Physiology and Pharmacology
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• v.2 no.4
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• pp.461-469
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• 1998

Tetrahydroisoquinoline (THI) alkaloids can be considered as cyclized derivatives of simple phenylethy-lamines, and many of them, especially with 6,7-disubstitution, demonstrate relatively high affinity for catecholamines. Two -OH groups at 6 and 7 positions are supposed to be essential to exert ?${\beta}-receptor$ activities. However, it is not clear whether -OH at 6,7 substitution of THIs also shows ?${\alpha}-adrenoceptor$ activities. In the present study, we investigated whether -OH or $-OCH_3$ substitutions of 6,7 position of THIs differently affect the ?1-adrenoceptor affinity. We synthesized two 1-naphthylmethyl THI alkaloids, $1-{\beta}-naphthylmethyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline$ HBr (YS 51) and $1-{\beta}-naphthylmethyl-6, 7-dimethoxy-1,2,3,4-tetrahydroisoquinoline$ HCl (YS 55), and their pharmacological actions on ?${\alpha}_1-adrenoceptor$ were compared. YS 51 and YS 55, concentration-dependently relaxed endothelium-denuded rat thoracic aorta precontracted with phenylephrine (PE, 0.1 ${\mu}M$) in which $pEC_{50}$ were $5.89{\pm}0.21$ and $5.93{\pm}0.19$, respectively. Propranolol (30 nM) did not affect the relaxation-response curves to YS 51 and YS 55. Concentration-response curves to PE were shifted to right by the pretreatment with YS 51 or YS 55. The $pA_2$ values of YS 51 and YS 55 showed $6.05{\pm}0.24$ and $5.88{\pm}0.16$, respectively. Both probes relaxed KCl (65.4 mM)-contracted aorta and inhibited $CaCl_2-induced$ contraction of PE-stimulated endothelium- denuded rat thoracic aorta in $Ca^{2+}-free$ solutions. In isolated guinea pig papillary muscle, 1 and 10 ${\mu}M$ YS 51 increased contractile force about 4- and 8- fold over the control, respectively, along with the concentration-dependent increment of cytosolic $Ca^{2+}$ ions. While, 10 ${\mu}M$ YS 55 reduced the contractile force about 50 % over the control and lowered the cytosolic $Ca^{2+}$ level, in rat brain homogenates, YS 51 and YS 55 displaced $[^3H]prazosin$ binding competitively with Ki 0.15 and 0.12 ${\mu}M$, respectively. However, both probes were ineffective on $[^3H]nitrendipine$ binding. Therefore, it is concluded that two synthetic naphthylmethyl-THI alkaloids have considerable affinity to ?1-adrenenoceptors in rat aorta and brain.

• YAKHAK HOEJI
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• v.34 no.3
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• pp.180-191
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• 1990

A comparison was made of the effects of selective ${\alpha_1}-adrenoceptor$ agonist phenylephrine and selective ${\alpha_2}-adrenoceptor$ agonist clonidine on endothelium-containing and endothelium-denuded rings of the rat aorta. In the case of phenylephrine, removal of endothelium increased sensitivity 2.5 fold at $EC_{50}$ level and maximum contractive response 1.4 fold. In the case of clonidine, which gave only 15% of maximum contractive response given to phenylephrine on endothelium-containing rings, removal of the endothelium increased sensitivity 5.6 fold at $EC_{50}$ level and maximum contractive response 5 fold, which was about 55% of that given by phenylephrine. In endothelium-denuded ring, phenylephrine-induced contraction tended to be more increased in tonic contraction than in phasic contraction as compared to that in endothelium-containing ring, while clonidine-induced contraction was monophasic and was increased only in tonic contraction. In the calcium-free solution or in the presence, of verapamil, contraction stimulated by clonidine was almost abolished while that stimulated by phenylephrine produced only phasic contraction. The depression of sensitivity to these agonists in rings with endothelium appeared to be due to the vasodepressor action of endothelium derived relaxing factor (EDRF), because hemoglobin, a specific blocking agent of EDRF, abolished this depression. It is unlikely that the endothelium-dependent relaxation was due to stimulation of release of EDRF, because clonidine did not produce endothelium-dependent relaxation in 5-hydroxytryptamine-precontracted ring even when its contractile action was blocked by the ${\alpha_1}-adrenoceptor$ antagonist, prazosin. When the efficacy of phenylephrine was reduced to about the initial efficacy of clonidine by pretreatment with dibenamine, the contraction-response curves for phenylephrine became very similar to the corresponding curves obtained for clonidine before receptor inactivation. In the dibenamine-treated rings, contraction of phenylephrine was abolished in calcium-free solution or in the presence of verapamil like that obtained for clonidine before receptor inactivation. These results suggest that EDRF spontaneously released from endothelium depress contraction more profoundly in a case of an agonist with low efficacy and the phenylephrine-induced contraction was totally dependent on extracellular calcium as was that obtained for clonidine when the efficacy of phenylephrine was reduced to that of clonidine by irreversible inactivation of ${\alpha_1}-adrenoceptor$ with dibenamine.

• Journal of the Korean Society of Food Science and Nutrition
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• v.22 no.2
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• pp.222-225
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• 1993

To obtain a thermal diffusivity predicting equation for meat products, minced pork meat was mixed with some additives such as lard, isolated soybean protein, 1.5% of table salt and 2% of polyphosphate to control the composition and texture of the products and then stuffed in a model can. Heat penetration curves were measured in the temperature range of 80.76~121.03$^{\circ}C$ by using a thermocouple fixed at the cold point of the model can and the thermal diffusivities were calculated from the plotted heat penetration curves. At constant heating temperature, the thermal diffusivities of pork meat with water content of 49.01~77.55% increased linearly with increasing water content. The thermal diffusivities of the products with constant water content also increased linearly with increasing heating temperature and the values could be predicted by following equation: $\alpha$p=(2.1394+0.5X$_{w}$).$\alpha$$_{w}$+0.0035.10$^{-6}$ .X$_{w}$-0.2785.10$^{-6}$ ,(m$^2$.s$^{-1}$ ). The maximal difference of the values predicted with this equation on the basis of the practical measured values were less than 1.7%. 1.7%.

• The Korean Journal of Pain
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• v.29 no.4
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• pp.229-238
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• 2016

Background: The goal of this in vitro study was to investigate the effect of lipid emulsion on vasodilation caused by toxic doses of bupivacaine and mepivacaine during contraction induced by a protein kinase C (PKC) activator, phorbol 12,13-dibutyrate (PDBu), in an isolated endothelium-denuded rat aorta. Methods: The effects of lipid emulsion on the dose-response curves induced by bupivacaine or mepivacaine in an isolated aorta precontracted with PDBu were assessed. In addition, the effects of bupivacaine on the increased intracellular calcium concentration ($[Ca^{2+}]_i$) and contraction induced by PDBu were investigated using fura-2 loaded aortic strips. Further, the effects of bupivacaine, the PKC inhibitor GF109203X and lipid emulsion, alone or in combination, on PDBu-induced PKC and phosphorylation-dependent inhibitory protein of myosin phosphatase (CPI-17) phosphorylation in rat aortic vascular smooth muscle cells (VSMCs) was examined by western blotting. Results: Lipid emulsion attenuated the vasodilation induced by bupivacaine, whereas it had no effect on that induced by mepivacaine. Lipid emulsion had no effect on PDBu-induced contraction. The magnitude of bupivacaine-induced vasodilation was higher than that of the bupivacaine-induced decrease in $[Ca^{2+}]_i$. PDBu promoted PKC and CPI-17 phosphorylation in aortic VSMCs. Bupivacaine and GF109203X attenuated PDBu-induced PKC and CPI-17 phosphorylation, whereas lipid emulsion attenuated bupivacaine-mediated inhibition of PDBu-induced PKC and CPI-17 phosphorylation. Conclusions: These results suggest that lipid emulsion attenuates the vasodilation induced by a toxic dose of bupivacaine via inhibition of bupivacaine-induced PKC and CPI-17 dephosphorylation. This lipid emulsion-mediated inhibition of vasodilation may be partly associated with the lipid solubility of local anesthetics.

• The Korean Journal of Physiology and Pharmacology
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• v.24 no.4
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• pp.339-348
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• 2020

We aimed to characterize the participation of rapid non-genomic and delayed non-genomic/genomic or genomic mechanisms in vasoactive effects to triiodothyronine (T3), emphasizing functional analysis of the involvement of these mechanisms in the genesis of nitric oxide (NO) of endothelial or muscular origin. Influences of in vitro and in vivo T3 treatments on contractile and relaxant responsiveness of isolated rat aortas were studied. In vivo T3-treatment was 500 ㎍·kg^-1·d^-1, subcutaneous injection, for 1 (T3_1d) and 3 (T3_3d) days. In experiments with endothelium-intact aortic rings contracted with phenylephrine, increasing concentrations of T3 did not alter contractility. Likewise, in vitro T3 did not modify relaxant responses induced by acetylcholine or sodium nitroprusside (SNP) nor contractile responses elicited by phenylephrine or angiotensin II in endothelium-intact aortas. Concentration-response curves (CRCs) to acetylcholine and SNP in endothelium-intact aortic rings from T3_1d and T3_3d rats were unmodified. T3_3d, but not T3_1d, treatment diminished CRCs to phenylephrine in endothelium-intact aortic rings. CRCs to phenylephrine remained significantly depressed in both endothelium-denuded and endothelium-intact, nitric oxide synthase inhibitor-treated, aortas of T3_3d rats. In endothelium-denuded aortas of T3_3d rats, CRCs to angiotensin II, and high K⁺ contractures, were decreased. Thus, in vitro T3 neither modified phenylephrine-induced active tonus nor CRCs to relaxant and contractile agonists in endothelium-intact aortas, discarding rapid non-genomic actions of this hormone in smooth muscle and endothelial cells. Otherwise, T3_3d-treatment inhibited aortic smooth muscle capacity to contract, but not to relax, in an endothelium- and NO-independent manner. This effect may be mediated by delayed non-genomic/genomic or genomic mechanisms.

• Journal of Physiology & Pathology in Korean Medicine
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• v.17 no.2
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• pp.493-498
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• 2003

Paeoniae Radix, Glycyrrhizae Radix and Jakyakgamchotang have been used in Oriental Medicine for many centuries as a treatment for various disease. The purpose of the present study is to determine the effect of Paeoniae Radix, Glycyrrhizae Radix and Jakyakgamchotang on narepinephrine(NE) induced contraction of isolated rabbit femoral artery. Rabbits (2.0kg, female) were killed by CO₂ exposure and a segment (8-10mm) of the aortic ring from each rabbit was cut into equal segments and mounted 'in pairs' in a tissue bath. Contractile force was measured with force displacement transducers under 1.5g loading tension. The dose of NE which evoked 50% of maximal response (ED/sub 50/) was obtained from cumulative dose response curves for NE (10/sup -7/～10/sup -4/M). Contractions evoked by NE (ED/sub 50/) were inhibited significantly by Paeoniae Radix, Glycyrrhizae Radix and Jakyakgamcho-tang. The mean percent inhibition of NE induced contraction was 83.9% (p<0.01) after 150㎕/㎖ Paeoniae Radix, 101.1 %(p<0.01) after 150 ㎕/㎖, Glycyrrhizae Radix and 107.3%(p<0.01) after 150㎕/㎖ Jakyakgamcho-tang, Indomethacin slightly but significantly attenuated the inhibitory effects of Paeoniae Radix. Following treatment with indomethacin, the mean percent inhibition caused by 150㎕/㎖ Paeoniae Radix fell to 16.4% in femoral artery induced by NE contraction. Propranolol, ODQ, and L-NNA did not significantly alter the inhibitory effect of Paeoniae Radix. ODQ slightly but significantly attenuated the inhibitory effects of Glycyrrhizae Radix. Following treatment with ODQ, the mean percent inhibition caused by 150㎕/㎖ Glycyrrhizae Radix fell to 13.0% in femoral artery induced by NE contraction. Propranolol, indomethacin and L-NNA did not significantly alter the inhibitory effect of Glycyrrhizae Radix. L-NNA slightly but significantly attenuated the inhibitory effects of Jakyakgamchotang. Following treatment with L-NNA, the mean percent inhibition caused by 150㎕/㎖ Jakyakgamchotang fell to 13.8% in femoral artery induced by NE contraction. Propranolol, ODQ and indomethacin did not significantly alter the inhibitory effect of Jakyakgamcho-tang. These results indicate that Paeoniae Radix, Glycyrrhizae Radix and Jakyakgamcho-tang can relax NE induced contraction of the isolated rabbit femoral artery, and that this inhibition related to nitric oxide.

• The Korean Journal of Food And Nutrition
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• v.10 no.1
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• pp.110-116
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• 1997

Growth curves of seven strains of lactic acid bacteria isolated from Kimchi were graphed during cultivation at 1$0^{\circ}C$, 2$0^{\circ}C$, 3$0^{\circ}C$ and 4$0^{\circ}C$ in filter sterilized Chinese cabbage juice, and then lag time and generation time at each conditions were calcurated. At 3$0^{\circ}C$, the lag time of Leu. mesenteroides subsp. dextranicum was 168 min(minutes), Leu. mesenteroides subsp. mesenteroides 204 min, Leu. paramesenteroides 612 min, Lac. bavaricus 258 min, Lac. homohiochii 228 min, Lac. plantarum 270 min and Lac. brevis 264 min. And at this temperature, the generation times of Leu. mesenteroides subsp. dextranicum and Leu. mesenteroides subsp. mesenteroides were all 36 min, Lac. bavaricus 33 min, Lac. homohiochii 39 min, Lac. plantarum 66 min, Lac. brevis 42 min and Leu. paramesenteroides 162 min. As cultural temperature was lowed from 3$0^{\circ}C$ to 1$0^{\circ}C$, all strains showed remarkable prolongations in lag time and in generation time, and the prolongations were most conspicuous in Lac. plantarum. At 1$0^{\circ}C$, 2$0^{\circ}C$ and 3$0^{\circ}C$, both the lag time and the generation time of Leu. mesenteroides subsp. mesenteroides were shorter than those of Lac. plantarum. But at 4$0^{\circ}C$, this pattern was completely inverted. As a whole lower temperatures were more favorable for the growth of Leu. mesenteroides subsp. mesenteroides, while higher temperatures were for Lac. plantarum.

• The Korean Journal of Physiology and Pharmacology
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• v.2 no.3
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• pp.323-330
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• 1998

Tetrahydroisoquinoline (THI) alkaloids can be considered as cyclized derivatives of simple phenylethylamines. Many of them, especially with 6,7-disubstitution, demonstrate a relatively high affinity for catecholamines. Present study examines the pharmacological action of limited series of THI, using rats' isolated atria and aorta. In addition, a $[^3H]$ prazosin displacement binding study with THI compounds was performed, using rat brain homogenates to investigate whether these probes have ?${\alpha}$-adrenoceptor affinity. We also compared the vascular relaxation potency of these probes with dobutamine. YS 49, YS 51, higenamine and dobutamine, concentration-dependently, relaxed endothelium-denuded rat thoracic aorta precontracted with phenylephrine (PE, 0.1 ${\mu}M$) in which $pEC_{50}$ were $5.56{\pm}0.32$ and $5.55{\pm}0.21$, $5.99{\pm}1.16$ and $5.57{\pm}0.34$, respectively. These probes except higenamine also relaxed KCl (65.4 mM)-contracted aorta. In isolated rat atria, all THIs and dobutamine increased heart rate and contractile force. In the presence of propranolol, the concentration response curves of YS 49 and YS 51 shifted to the right and resulted in $pA_2$ values of $8.07{\pm}0.84$ and $7.93{\pm}0.11$, respectively. The slope of each compound was not deviated from unity, indicating that these chemicals are highly competitive at the cardiac ?${\beta}-adrenoceptors$. YS 49, YS 51, and higenamine showed ?${\alpha)-adrenoceptor$ affinity in rat brain, in which the dissociation constant $(K_i)$ was 2.75, 2.81, and 1.02 ${\mu}M$, respectively. It is concluded, therefore, that THI alkaloids have weak affinity to ${\alpha)_1-adrenoceptor$ in rat aorta and brain, respectively, while these probes show relatively high affinity for cardiac ${\beta}-adrenoceptors$. Thus, these chemicals may be useful in the treatment of congestive heart failure.

• Journal of the Korea institute for structural maintenance and inspection
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• v.23 no.6
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• pp.77-83
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• 2019

Upon installing a seismic isolation device on a nuclear power plant, the device takes on the suppression of seismic loads. This is expected to bring about a larger displacement than what is seen prior to the installation of the seismic isolation device. Depending on the displacement change, the seismic risk for some equipment can increase. Particularly in case of the piping system, which is used for connecting the structure isolated from seismic events with common structures, the seismic risk is expected to rise significantly. In this study, the limit state of the steel pipe tee, which is a vulnerability part of the nuclear power plant piping system, was defined as leakage, and an in-plane cyclic loading test was conducted. As it is difficult to measure the moment and rotation of the steel pipe tee using the conventional sensors, an image signal was used. This study proposed a leakage line and low-cycle fatigue curves using the relationship between the moment and the rotation of a 3-inch steel pipe tee.