• The Korean Journal of Pharmacology
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• v.32 no.1
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• pp.39-49
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• 1996

In the present study, we observed change in intracellular $Ca^{2+}$$([Ca^{2+}]_i)$ as measured with the fluorescent $Ca^{2+}-indicator$ fura-2 in association with force development of the rat basilar arteries during activation by$K^+$ depolarizing solution and U46619, a thromboxane analogue, in the absence and the presence of calcitonin-gent related peptide (CGRP). CGRP (30 and 100 nM) caused a concentration-dependent inhibition of U46619-induced contraction with decrease in $[Ca^{2+}]_i$, whereas it did not exert any effect on the $K^+$ (90 mM)-induced contraction and increase in $[Ca^{2+}]_i$, Further, $[Ca^{2+}]_i-force$ relationships were determined by plotting the ratio of $F_{340}/F_{380}$ $([Ca^{2+}]_i)$ as a function of the force induced by U46619, and the results were compared with those obtained in the presence of CGRP. The curves obtained in the presence of CGRP (30 and 100 nM) were significantly moved to downward without right shift of the curves suggesting that CGRP inhibited the U46619-induced contraction only by mediation of reduction in $[Ca^{2+}]_i$ with out any change in the sensitivity of contractile apparatus to $Ca^{2+}$. The CGRP-induced attenuation of $[Ca^{2+}]_i$ and force development was significantly inhibited under pretreatment with CGRP $(8{\sim}37)$ fragment (100 nM), a CGRP1 receptor antagonist. Both the reduced contraction and reduction in $[Ca^{2+}]_i$ caused by CGRP were fully reversed by pretreatment with charybdotoxin (100 nM) and iberiotoxin (100 nM), large conductance $Ca^{2+}-activated$ $K^+$ channel blockers, but not by apamin (300 nM), a small conductance $Ca^{2+}-activated$ $K^+$ channel blocker, and glibenclamide ( 1 ${\mu}M$), an ATP-sensitive $K^+$ channel blocker. In conclusion, it is suggested that the CGRP1 receptor, upon activation by CGRP, are coupled to opening of $Ca^{2+}-activated$ $K^+$ channel and cause to decrease in $[Ca^{2+}]_i$, thereby leading to vasodilation of the rat basilar artery. However, it is not defined that the mechanism underlying vasodilation whether the $K^+$ channel blockers, charybdotoxin and iberiotoxin directly block the CGRP receptors and that CGRP-evoked relaxation is dependent on the cyclic AMP or $K^+$ channel opening or both actions.

• The Korean Journal of Pharmacology
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• v.32 no.1
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• pp.23-29
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• 1996

According to the traditional receptor model, competitive antagonists share with agonists the ability to bind to a common site on receptors, but they are different from agonist in that they cannot trigger the biological response-i.e., they lack intrinsic efficacy. Recent findings extend the model by indicating that not all antagonists display an intrinsic efficacy of zero but that some display 'inverse agonism'. In the present study we studied the inverse agonism at $A_1$ adenosine receptors in membranes prepared from rat cerebral cortex. Eight commercially available $A_1$ adenosine receptor antagonists (CGS-15943, ADPX, CPT, DPCPX, DPX, N-0840, PACPX and 8-PT) were screened for inverse agonism by measuring the extent of $[^{35}S]guanosine-5'-({\gamma}-thio)$ triphosphate $([^{35}S]GTP_{\gamma}S)$ binding to G proteins. The agonist-induced stimulation of $[^{35}S]GTP_{\gamma}S$ bindings was completely blocked in the presence of $A_1$ adenosine receptor antagonists. Under optimal conditions, two types of antagonists could be distinguished. Seven antagonists including DPCPX decreased the basal $[^{35}S]GTP_{\gamma}S$ binding in the absence of agonist, displaying inverse agonist activity. One (CGS-15943) had no effect on the basal bindings. N-ethylmaleimide treatment reduced the basal bindings as well as agonist-mediated stimulation of $[^{35}S]GTP_{\gamma}S$ bindings, indicating that a substantial amount of this binding reflects an activated state of the C proteins. In good agreement with these findings, 0.1 mM GTP decreased the apparent affinity of the receptors for the agonist PIA, increased that for DPCPX, and had no effect on that for CGS-15943.

• The Korean Journal of Pharmacology
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• v.21 no.2
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• pp.119-127
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• 1985

The renal function is under regulatory influence of the central nervous system, mainly through activation of sympathetic nerve to the kidney, and it was recently reported that clonidine, an agonist to ${\alpha}_2$-adrenoceptors, induces diuresis and natriuresis when injected directly into a lateral ventricle of the rabbit brain (i.c.v.). This study was undertaken, therefore, to obtain further information as to the role of the central ${\alpha}_2$-adrenoceptors in regulating renal function, by observing the effects of i.c.v. yohimbine, a specific antagonist of adrenoceptors of ${\alpha}_2$-type, on the rabbit renal function, and to elucidate the mechanism involved in it. With 10 ${\mu}g/kg$ i.c.v. of yohimbine sodium excretion transiently increased along with increasing tendency of urine flow, renal plasma flow and glomerular filtration rate. These responses decreased with increasing doses. With 100 and 300 ${\mu}g/kg$ i.c.v. marked antidiuresis and antinatriuresis as well as profound decreases of renal perfusion and glomerular filtration were noted. Systemic blood pressure transiently increased. In reserpinized rabbits, 100 ${\mu}g/kg$ yohimbine i.c.v. did not produce any significant changes in urine flow, sodium excretion as well as in renal hemodynamics. The pressor response was also abolished. In preparations in which one kidney was denervated and the other left intact as control, i.c.v. yohimbine elicited typical antidiuretic antinatriuretic response in the innervated control kidney, whereas the denervated experimental kidney responded with marked diuresis and increases in excretory rates of sodium and potassium and in osmolar clearance in spite of absence of increased filtration and perfusion . Systemic blood pressure responded as in the normal rabbits. These observations indicate that i.c.v. yohimbine affects renal function in dual ways in opposite directions, the first being the antidiuretic antinatriuretic effects which results from decreased renal perfusion and glomerular filtration due to sympathetic activation and which is predominantly expressed in the normal rabbits, and the second less apparent effect being the diuretic and natriuretic action which is not mediated by nerve pathway but brought about by some humoral mechanism and which is effected by decreased sodium reabsorption in the tubules, possibly of the proximal portion.

• The Korean Journal of Pharmacology
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• v.21 no.2
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• pp.128-141
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• 1985

To investigate the influence of phenobarbital sodium on the action of morphine and on the diurnal rhythms of both opiate receptor binding and ${\beta}-endorphin$ contents, the amount of specifically bound $(^3H)$-morphine and immunoreactive ${\beta}-endorphin$ were measured in the midbrain of phenobarbital-treated rats at 4h intervals in a day. Rats were housed and adapted to a controlled cycle of either 12 h light-12 h dark or 24 h constant dark. After 3 weeks of adaptation, 0.5 ml of physiological saline or phenobarbital sodium (20mg/kg/day, i.p.) were administered twice a day for 2 weeks. Highly significant diurnal rhythms of opiate receptor binding and ${\beta}-endorphin$ were present in rat midbrain. In control group, the peak of maximum $(^3H)$-morphine binding was observed at 22:00 h, whereas the peak of ${\beta}-endorphin$ content was found at 06:00 h. Even in the absence of time cues these diurnal rhythms persisted, but they were highly modified with respect to the wave form as well as differences in the timing of peak and nadir. In the phenobarbital-treated group, these diurnal rhythms were also modified in shape, phase and amplitude, as well as in timing of peak and nadir. In this group, 24 h mean of opiate receptor binding was significantly decreased, while the 24 h mean level of ${\beta}-endorphin$ content was highly increased. However, Kd values in all experimental groups did not change. This indicates that differences in binding were not due to changes in the affinity, but in the number of binding sites. Statistical analysis of regression line indicates that changes of receptor binding were closely correlated with the changes of ${\beta}-endorphin$ content. These results suggest that phenobarbital may influence the action of morphine by changing the number of opiate receptors and that the modification of diurnal rhythm of opiate receptor by the agent is possibly due to changes of ${\beta}-endorphin$ content.

• Korean Security Journal
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• no.37
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• pp.325-354
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• 2013

The concept of national security and the fundamental system for crisis management have departed from traditional methods and the importance of a national critical infrastructure crisis management has been emphasized. A national critical infrastructure crisis means a situation where human resource, material and functional system that may have a material effect on the critical functions of the government, the vitality and integrity of society, national economy and the safety of the public becomes disabled due to causes such as terrorism or major disasters. Although North Korea had been subject to numerous rounds of negotiations and sanctions as it continually developed nuclear weapons since the 1960s, it has also showed off its nuclear armaments through successful nuclear testings and missile launches. As the development and threat of North Korea's weapons of mass destruction becomes more noticeable and the range of its risk expands, this study focuses on the potential for an absence of leadership for national crisis management where the country's leadership, which should serve the critical role and function of handling national crises, becomes completely destroyed by the unexpected initial attacks by North Korea. As a result, the purpose of this study is to propose safety measures for the country's leadership in preparation for North Korea's threat of nuclear weapons by examining the concept and degree of risk of weapons of mass destruction with a focus on nuclear weapons, analyzing the substance of the threat of North Korean nuclear weapons and evaluating such threat. In conclusion, first, to ensure the normal functioning of a national crisis management system in the event of a national crisis, we must seek safety measures that conform to the scope and succession order of the leadership of the national crisis management for an Enduring Constitutional Government (ECG) and the Continuity Of Operations (COOP). Second, in the event of a national ceremony, the gathering of the country's leadership all together in an open place should be avoided. In unavoidable circumstances, the next in rank that will act on behalf of the current leader should be designated and relevant safety measures should be taken. Third, during time of peace, in preparation for national crises, the scope of protection for the country's leadership should be prescribed and specific security and safety measures should be implemented. Fourth, the succession order for acting president in the case of the death of the president pursuant to Articles 71 and 26(1) of the National Government Organization Act should reconsidered to see whether it is a reasonable provision that takes into consideration a national crisis management that corresponds to the threat of North Korean nuclear weapons and weapons of mass destruction. Pursuant to the Basic Guidelines for National Crisis Management set out under Presidential Directive No. 229, the Korean government is currently operating a case-by-case "crisis management standard manual" and its sub-manuals and has also prepared the Presidential Security Service's security and safety measure regulations regarding the acting president. Therefore, the Korean government should actualize the above points in the case-by-case crisis management standard manual and security and safety measure regulations regarding the acting president to implement and legislate them.

• Journal of Veterinary Clinics
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• v.23 no.2
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• pp.105-110
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• 2006

A three-layer, feed-forward artificial neural network (ANN) with sixteen input neurons, three hidden neurons, and one output neuron was developed to identify the presence of infectious bronchitis (IB) infection as early as possible in laying hen flocks. Retrospective data from flocks that enrolled IB surveillance program between May 2003 and November 2005 were used to build the ANN. Data set of 86 flocks was divided randomly into two sets: 77 cases for training set and 9 cases for testing set. Input factors were 16 epidemiological findings including characteristics of the layer house, management practice, flock size, and the output was either presence or absence of IB. ANN was trained using training set with a back-propagation algorithm and test set was used to determine the network's capability to predict outcomes that it has never seen. Diagnostic performance of the trained network was evaluated by constructing receiver operating characteristic (ROC) curve with the area under the curve (AUC), which were also used to determine the best positivity criterion for the model. Several different ANNs with different structures were created. The best-fitted trained network, IBV_D1, was able to predict IB in 73 cases out of 77 (diagnostic accuracy 94.8%) in the training set. Sensitivity and specificity of the trained neural network was 95.5% (42/44, 95% CI, 84.5-99.4) and 93.9% (31/33, 95% CI, 79.8-99.3), respectively. For testing set, AVC of the ROC curve for the IBV_D1 network was 0.948 (SE=0.086, 95% CI 0.592-0.961) in recognizing IB infection status accurately. At a criterion of 0.7149, the diagnostic accuracy was the highest with a 88.9% with the highest sensitivity of 100%. With this value of sensitivity and specificity together with assumed 44% of IB prevalence, IBV_D1 network showed a PPV of 80% and an NPV of 100%. Based on these findings, the authors conclude that neural network can be successfully applied to the development of a screening model for identifying IB infection in laying hen flocks.

• Journal of Physiology & Pathology in Korean Medicine
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• v.17 no.2
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• pp.529-541
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• 2003

Yukmijihwang-tang has been widely used as an and-aging herbal medicine for hundred years in Asian countries. Numerous studies show that Yukmijihwangtang has anti-oxidative effect both in vivo and in vitro. It has been reported that Moutan Cortex Radicis extract (MCR) was the most effective herb in Yukmijihwang-tang on undifferentiated PC12 cells upon oxidative-stressed with hydrogen peroxide. The purpose of this study is to; 1) evaluate the recovery of neuronal damage by assessing the anti-oxidant effect of MCR on PC12 cells differentiated with nerve growth factor (NGF), 2) identify candidate genes responsible for anti-oxidative effect on differentiated PC12 cells by oligonucleotide chip microarray. PC12 cells, which were differentiated by treating with NGF, were treated without or with hydrogen peroxide in the presence or absence of various concentration of MCR. Cell survival was determined by using MTS assay. Measurement of intracellular reactive oxygen species (ROS) generation was determined using the H2DCFDA assay The viability of cells treated with MCR was significantly recovered from stressed PC12 cell. In addition, wide rage of concentrations of MCR shows dose-dependent inhibitory effect on ROS production in oxidative-stressed cells. Total RNAs of cells without treatment(Control group), only treated with H₂O₂ (stressed group) and treated with both H₂O₂ and of MCR (MCR group) were isolated, and cDNAs was synthesized using oligoT7(dT) primer. The fragmented cRNAs, synthesized from cDNAs, were applied to Affymetrix GeneChip Rat Neurobiology U34 Array. mRNA of Calcium/calmodulin-dependent protein kinase II delta subunit(CaMKII), neuron glucose transporter (GLUT3) and myelin/oligodendrocyte glycoprotein(MOG) were downregulated in Stressed group comparing to Control group. P2X2-5 receptor (P2X2R-5), P2X2-4 receptor (P2X2R-4), c-fos, 25 kDa synaptosomal attachment protein(SNAP-25a) and GLUT3 were downregulated, whereas A2 adenosine receptor (A2AR), cathechol-O-methyltransferase(COMT), glucose transporter 1 (GLUT1), EST223333, heme oxygenase (HO), VGF, UI-R-CO-ja-a-07-0-Ul.s1 and macrophage migration inhibitory factor (MIF) were upregulated in MCA group comparing to Control group. Expression of Putative potassium channel subunit protein (ACK4), P2X2A-5, P2X2A-4, Interferon-gamma inducing factor isoform alpha precursor (IL-18α), EST199031, P2XR, P2X2 purinoceptor isoform e (P2X2R-e), Precursor interleukin 18 (IL-18) were downregulated, whereas MOO, EST223333, GLUT-1, MIF, Neuronatin alpha, UI-R-C0-ja-a-07-0-Ul.s1, A2. adenosine receptor, COMT, neuron-specific enolase (NSE), HO, VGF, A rat novel protein which is expressed with nerve injury (E12625) were upregulated in MCR group comparing to Stressed group. The results suggest that decreased viability and AOS production of PC12 cell by H₂O₂ may be, at lease, mediated by impaired glucose transporter expression. It is implicated that the MCR treatment protect PC12 cell from oxidative stress via following mechanisms; improving glucose transport into the cell, enhancing expression of anti-oxidative genes and protecting from dopamine cytotoxicity by increment of COMT and MIF expression. The list of differentially expressed genes may implicate further insight on the action and mechanism behind the anti-oxidative effects of herbal extract Moutan Cortex Radicis.

• Childhood Kidney Diseases
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• v.11 no.2
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• pp.220-228
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• 2007

Purpose : We studied the value of clinical signs, laboratory findings and $^{99m}technetium$ dime-rcaptosuccinic acid(DMSA) scan in predicting the presence of vesicoureteral reflux(VUR) in children with first febrile urinary tract infection(UTI). Methods : A retrospective analysis of 84 hospitalized children with first febrile UTI was performed. They underwent DMSA scan and voiding cystourethrography(VCUG) during the acute phase, and were divided into three groups according to the results of the VCUG: absence of VUR, mild(grade I-II) and severe VUR(grade III-V). We studied the relation of VUR to age, gender, fever duration, causative organism, white blood cell count, serum C-reactive protein and result of DMSA scan. Results : Among 84 patients, 6 had mild and 17 had severe VUR. Thirty-eight had abnormal DMSA scan. results Patients with VUR were older than those without VUR(P<0.01). There was a lower probability of infection with Escherichia coli in patients with severe VUR than in those with mild and absent VUR(P<0.01). An abnormal DMSA scan correlated with the presence and severity of VUR(P<0.05). Severe VUR was present in 10.9% of patients with normal DMSA scan. The sensitivity, specificity, positive and negative predictive values of the DMSA scan in predicting the presence of VUR were 69.6%, 63.9%, 42.1%, and 84.8%, respectively. Conclusion : An abnormal DMSA scan correlated to the presence and severity of VUR, but the sensitivity, specificity and positive predictive value of the DMSA scan were low. There-fore, patient with an abnormal DMSA scan requires a VCUG. In order to prevent missing the 10.9% of patients with severe VUR but normal DMSA scans, a VCUG should be performed in patient with normal DMSA scan.

• Journal of Life Science
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• v.25 no.1
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• pp.21-28
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• 2015

Genetic polymorphisms of adipocyte determination and differentiation factor 1 (ADD1) gene were screened in Hanwoo and Jeju Black cattle-derived commercial (JBC-DC) populations. The ADD1 genotypes were determined using the presence/absence of 84-bp fragment at intron 7 region. The association of ADD1 genotypes for economic traits was examined in both populations. In the Hanwoo steers, ADD1 D/- carcasses showed significantly thicker backfat levels than those from WW (p<0.05). However, the thickest level of backfat appeared in WD heterozygotes, whereas thicker backfat did not appear in DD homozygotes in the JBC-DC population (p<0.05), leading to the supposition that synergic effects of alleles W and D increase backfat deposition. On the other hand, there was no association between the ADD1 genotypes and intramuscular fat deposition measured as meat quality index and marbling score. From these results, we concluded that the bovine ADD1 affected the backfat in subcutaneous tissue, rather than intramuscular fat in muscle tissue. In addition, the DD animals showed higher levels of meat color than those from W/- (p<0.05). Interestingly, a highly significant difference was found between the genotypes and carcass weights only in the JBC-DC population, and D/- animals were heavier by more than 38 kg than those from WW (p<0.001). The results of this study reveal faster growth rate and differences in steer productivity according to genotypes of the ADD1 gene. These findings demonstrate that ADD1 genotypes may effectively function as molecular genetic markers for the improvement of Hanwoo and Jeju Black cattle-related crossbreeding systems.

• Journal of Life Science
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• v.25 no.12
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• pp.1408-1414
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• 2015

In this study, to retain a stable bacterial inoculant, Bacillus strains showing antifungal activity were screened. The improved production, antifungal mechanism, and stability of the antifungal metabolite by a selected strain, AF4, a potent antagonist against phytopathogenic Botrytis cinerea, were also investigated. The AF4 strain was isolated from rhizospheric soil of hot pepper and identified as Bacillus subtilis by phenotypic characters and 16S rRNA gene analysis. Strain AF4 did not produce antifungal activity in the absence of a nitrogen source and produced antifungal activity at a broad range of temperatures (25-40℃) and pH (7-10). Optimal carbon and nitrogen sources for the production of antifungal activity were glycerol and casein, respectively. Under improved conditions, the maximum antifungal activity was 140±3 AU/ml, which was higher than in the basal medium. Photomicrographs of strain AF4-treated B. cinerea showed morphological abnormalities of fungal mycelia, demonstrating the role of the antifungal metabolite. The B. subtilis AF4 culture exhibited broad antifungal activity against several phytopathogenic fungi. The antifungal activity was heat-, pH-, solvent-, and protease-stable, indicating its nonproteinous nature. These results suggest that B. subtilis AF4 is a potential candidate for the control of phytopathogenic fungi-derived plant diseases.