• Biomolecules & Therapeutics
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• v.4 no.2
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• pp.167-173
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• 1996

This study was undertaken to evaluate a behavior-electroencephalogram (EEG) pattern relationship in pilocarpine- and kainic acid-induced convulsions of rats. Also we intended to examine the effect of a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist, MK-801, and diazepam on the pilocarpine-induced behavioral and electrical seizures in rats. The electrical activities at frontal and hippocampal areas and behavior activities were measured in freely moving rats. At the beginning of the experiments, the rats displayed an exploratory behavior. This awake and moving phase with a low amplitude, irregular, 4-10 Hz wave was followed by a still phase. Pilocarpine (400 mg/kg, i.p.) and kainic acid (0.5 mg/kg, i.c.v.) induced tonic and clonic seizures. The pilocarpine-induced change in electrical activities exhibited a weak correlation with behavioral convulsion at all stages. The amplitude and duration of the electrical response were not linear with the degree of behavioral score. An application of MK-801 (dizocilpine, 7.5 mg/kg) did not affect the amplitudes of the convulsant-induced electrical activities, though the same dose of this drug caused the deformation of the electrical pattern. There was no effect of MK-801 on the behavioral and electrical activities as expected. Diazepam (1 mg/kg) did not affect the amplitude of the electrical activities induced by pilocarpine but changed the pattern of these activities. Our study shows that there is no linear relationship between degree of behavior and amplitude of electrical activities of convulsants. This may indicate that the NMDA receptor stimulation can be processed by the neocortical or hippocampal network in a different way between behavioral and electrical activities.

• Asian-Australasian Journal of Animal Sciences
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• v.22 no.5
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• pp.618-625
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• 2009

The objective of this work was to study the direct effects of daidzein on steroidogenesis in cultured mouse Leydig cells. Adult mouse Leydig cells were purified by Percoll gradient centrifugation, and the cell purity was determined using a $3{\beta}$-hydroxysteroid dehydrogenase ($3{\beta}$-HSD) staining method. The purified Leydig cells were exposed to different concentrations ($10^{-7}$ M to $10^{-4}$ M) of daidzein for 24 h under basal and human chorionic gonadotropin (hCG)-stimulated conditions. The cell viability and testosterone production were determined, and the related mechanisms of daidzein action were also evaluated using the estrogen receptor antagonist ICI 182,780 and measuring the mRNA levels of steroidogenic acute regulatory protein (StAR), cholesterol side-chain cleavage enzyme (P450scc), and $3{\beta}$-HSD-1 involved in testosterone biosynthesis. The results revealed that daidzein did not influence cell viability. Daidzein increased both basal and hCG-stimulated testosterone production in a dose-dependent manner, and this effect was statistically significant at concentrations of $10^{-5}$ M and $10^{-4}$ M daidzein (p<0.05). ICI 182,780 had no influence on daidzein action. RTPCR results revealed that $10^{-5}$ M and $10^{-4}$ M daidzein did not exert any obvious influence on the mRNA level of P450scc in Leydig cells. However, in the presence of hCG, these concentrations of daidzein significantly increased the StAR and $3{\beta}$-HSD-1 mRNA levels (p<0.05), but in the absence of hCG, only $10^{-5}$ M and $10^{-4}$ M daidzein up-regulated the StAR and $3{\beta}$-HSD-1 mRNA expression (p<0.05), respectively. These results suggest that daidzein has direct effect on Leydig cells. Daidzein-induced increase of testosterone production is probably not mediated by the estrogen receptor but correlates with the increased mRNA levels of StAR and $3{\beta}$-HSD-1.

• Childhood Kidney Diseases
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• v.9 no.2
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• pp.175-182
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• 2005

Purpose : Interleukin 1 receptor antagonist(IL-1ra) is an endogenous antiinflammatory agent that binds to IL-1 receptor and thus competitively inhibits the binding of IL-1$\alpha$ and IL-1$\beta$. Allele 2 in association with various autoimmune diseases has been reported. In order to evaluate the influence of IL-1ra gene VNTR polymorphism on the susceptibility to HSP and its possible association with disease severity, manifested by severe renal involvement and renal sequelae, we studied the incidence of carriage rate and allele frequency of the 2 repeats of IL-1ra allele 2($IL1RN^{*}2$) of the IL-1ra gene in children with HSP with and without renal involvement. Methods : The IL-1ra gene polymorphisms were determined in children with HSP with(n=40) or without nephritis(n=34) who had been diagnosed at Busan Paik Hospital and the control groups(n=163). Gene polymorphism was identified by PCR amplification of the genomic DNA. Results : The allelic frequency and carriage rate of $IL1RN^{*}1$ were found most frequently in patients with HSP and in controls. The allelic frequency of $IL1RN^{*}2$ was higher in patients with HSP compared to that of controls($4.7\%\;vs.\;2.5\%$, P=0.794). The carriage rate of $IL1RN^{*}2$ was higher In patients with HSP compared to that of controls($8.1\%\;vs.\;6.8\%$, P=0.916). The allelic frequency of $IL1RN^{*}2$ was higher in patients with HSP nephritis compared to that of HSP($5.3\%\;vs.\;2.9\%$, P=0.356). The carriage rate of $IL1RN^{*}2$ was higher in Patients with HSP nephritis compared to that of HSP($10.0\%\;vs.\;5.9\%$, P=0.523). Among 13 patients with heavy proteinuria(>1.0 g), 11 had $IL1RN^{*}1$, 1 had $IL1RN^{*}2$ and the others had $IL1RN^{*}4$. At the time of last follow up 4 patients had sustained proteinuria and their genotype was $IL1RN^{*}1$. Conclusion : The allelic frequency and carriage rate of $IL1RN^{*}1$ were found most frequently in patients with HSP and in controls. Our study suggests that the carriage rate and allele frequency of the 2-repeats of IL-1lra allele 2($IL1RN^{*}2$) of the IL-1ra gene may not be associated with susceptibility and severity of renal involvement in children with HSP (J Korean Soc Pediatr Nephrol 2005;9:175-182)

• Korean Journal of Acupuncture
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• v.32 no.1
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• pp.1-12
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• 2015

Objectives : The purpose of this study was to review the acupuncture and moxibustion therapy for gastroesophageal reflux disease(GERD) in China. Methods : The literatures were searched using the database-China Academic Journals(CAJ)(~2015.1.). Clinical studies of acupuncture and moxibustion therapy for GERD such as randomized controlled trial(RCT), non-randomized controlled trial(NRCT), case series, or case report were included. Results : Thirty studies met our inclusion criteria: 24 RCTs, 4 NRCTs, 1 case series, 1 case report. Various kinds of treatment such as body acupuncture, abdominal acupuncture, acupuncture therapy with finger on back-shu point, electroacupuncture, acupoint injection, auricular acupuncture, and moxibustion were used in the clinical studies. The treatment groups take herbal medicines at the same time in 16 studies, and proton pump inhibitor(PPI) and histamine 2 receptor antagonist were used as a comparative treatment in the most of studies. Acupuncture or moxibustion treatments were done daily or 2~3 times a week for 5 days~18 weeks. All of studies reported higher effective rate in the acupuncture or moxibustion treatment group compared to the western medication control group. Conclusions : The results of this study could be used for the future practice and the clinical research about the acupuncture and moxibustion therapy for GERD.

• Journal of Microbiology and Biotechnology
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• v.22 no.3
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• pp.378-384
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• 2012

In aquatic invertebrates, particularly marine gastropods, organotin compounds induce irreversible sexual abnormality in females, which is termed imposex, at very low concentrations. Organotin compounds are agonists for nuclear receptors such as RXRs and $PPAR{\gamma}$. However, the imposex phenomenon has not been reported to act as an antagonist on estrogen receptors in other species, including vertebrates and invertebrates. In order to gain insights into the antagonistic activity of organotin compounds on estrogen receptors (ERs), we examined the inhibitive effect of these compounds on estradiol-dependent ${\beta}$-galactosidase activity using the yeast two-hybrid detection system consisting of a combination of the human estrogen receptor ($hER{\beta}$) ligand-binding domain and the co-activator steroid receptor co-activator-1 (SRC1). Tributyltin-hydroxide (TBT-OH) and triphenyltin-chlorine (TPT-Cl) exhibited an inhibitive effect on $E_2$-dependent transcriptional activity, similar to antagonistic chemicals such as 4-hydroxytamoxifen (OHT) or ICI 182,780, at a very low concentration of $10^{-14}$ M TBT or $10^{-10}$ M TPT, respectively. The yeast growth and transcriptional activity with transcriptional factor GAL4 did not exhibit any effect at the tested concentration of TBT or TPT. Moreover, the yeast two-hybrid system using the interaction between p53 and the T antigen of SV40 large did not describe any effect at the tested concentration of OHT or ICI 182,780. However, the interaction between p53 and T antigen was inhibited at a TBT or TPT concentration of $10^{-9}$ M, respectively. These results indicate that TBT and TPT act as inhibitors of ER-dependent reporter gene transcriptional activation and of the interaction between $hER{\beta}$ LBD and the co-activator SRC1 in the yeast two-hybrid system. Consequently, our data could partly explain the occurrence of organotin compound-induced imposex on the endocrine system of mammals, including humans.

• Clinical and Experimental Pediatrics
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• v.56 no.7
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• pp.271-274
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• 2013

Brain insults, including neurotrauma, infection, and perinatal injuries such as hypoxic ischemic encephalopathy, generate inflammation in the brain. These inflammatory cascades induce a wide spectrum of cytokines, which can cause neuron degeneration, have neurotoxic effects on brain tissue, and lead to the development of seizures, even if they are subclinical and occur at birth. Cytokines are secreted by the glial cells of the central nervous system and they function as immune system mediators. Cytokines can be proinflammatory or anti-inflammatory. Interleukin (IL)-$1{\beta}$ and IL-8 are proinflammatory cytokines that activate additional cytokine cascades and increase seizure susceptibility and organ damage, whereas IL-1 receptor antagonist and IL-10 act as anti-inflammatory cytokines that have protective and anticonvulsant effects. Therefore, the immune system and its associated inflammatory reactions appear to play an important role in brain damage. Whether cytokine release is relevant for the processes of epileptogenesis and antiepileptogenesis, and whether epileptogenesis could be prevented by immunomodulatory treatment should be addressed in future clinical studies. Furthermore, early detection of brain damage and early intervention are essential for the prevention of disease progression and further neurological complications. Therefore, cytokines might be useful as biomarkers for earlier detection of brain damage in high-risk infants.

• Tuberculosis and Respiratory Diseases
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• v.42 no.5
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• pp.744-751
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• 1995

Background: Asthma is an inflammatory disease because there are many inflammatory changes in the asthmatic airways. Axon reflex mechanisms may be involved in the pathogenesis of asthma. Sensory neuropeptides are involved in this inflammation, which is defined as neurogenic inflammation. Substance p, neurokinin A, and neurokinin B may be main neuropeptides of neurogenic inflammation in airways. These tachykinins act on neurokinin receptors. Three types of neurokinin receptors, such as $NK_1$, $NK_2$, and $NK_3$, are currently recognized, at which substance p, neurokinin A, and neurokinin B may be the most relevant natural agonist of neurogenic inflammation in airways. The receptor subtypes present in several tissues have been characterized on the basis of differential sensitivity to substance p, neurokinin A, and neurokinin B. Plasma extravasation and vasodilation are induced by substance p more potently than by neurokinin A, indicating NK1 receptors on endothelial cells mediate the response. But airway contraction is induced by neurokinin A more potently than by substance P, indicating the $NK_2$ receptors in airway smooth muscles. These receptors are used to evaluate the pathogenesis of brochial asthma. FK224 was identified from the fermentation products of Streptomyces violaceoniger. FK224 is a dual antagonist of both $NK_1$ and $NK_2$ receptors. Purpose: For a study of pathogenesis of bronchial asthma, the effect of FK224 on plasma extravasation induced by vagal NANC electrical stimulation was evaluated in rat airway. Method: Male Sprague-Dawley rats weighing 180~450gm were anesthetized by i.p. injection of urethane. Plasma extravasation was induced by electrical stimulation of cervical vagus NANC nerves with 5Hz, 1mA, and 5V for 2 minutes(NANC2 group) and for sham operation without nerve stimulation(control group). To evaluate the effect of FK224 on plasma extravasation in neurogenic inflammation, FK224(1mg/kg, Fujisawa Pharmaceutical Co., dissolved in dimethylsulphoxide; DMSO, Sigma Co.) was injected 1 min before nerve stimulation(FK224 group). To assess plasma exudation, Evans blue dye(20mg/kg, dissolved in saline) was used as a plasma marker and was injected before nerve stimulation. After removal of intravascular dye, the evans blue dye in the tissue was extracted in formamide($37^{\circ}C$, 24h) and quantified spectrophotometrically by measuring dye absorbance at 629nm wavelength. Tissue dye content was expressed as ng of dye per mg of wet weight tissue. The amount of plasma extravasation was measured on the part of airways in each groups. Results: 1) Vagus nerve(NANC) stimulation significantly increased plasma leakage in trachea, main bronchus, and peripheral bronchus compared with control group, $14.1{\pm}1.6$ to $49.7{\pm}2.5$, $17.5{\pm}2.0$ to $38.7{\pm}2.8$, and $12.7{\pm}2.2$ to $19.1{\pm}1.6ng$ of dye per mg of tissue(mean ${\pm}$ SE), respectively(p<0.05). But there was not significantly changed in lung parenchyma(p>0.05) 2) FK224 had significant inhibitory effect upon vagal nerve stimulation-induced airway plasma leakage in any airway tissues of rat,such as trachea, main bronchus, and peripheral bronchus compared with vagus nerve stimulation group, 49%, 58%, and 70%, respectively(p<0.05). Inhibitory effect of FK224 on airway plasma leakage in neurogenic inflammation was revealed the more significant in peripheral bronchus, but no significant in lung parenchyma. Conclusion: These results suggest that FK224 is a selective NK receptor antagonist which effectively inhibits airway plasma leakage induced by the endogenous neurotransmitters relased by neurogenic inflammation in rat airway. Tachykinin receptor antagonists may be useful in the treatment of brochial asthma.

• Proceedings of the SCSK Conference
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• 2003.09a
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• pp.578-589
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• 2003

The fuzzy rat that expresses hypersecretion of sebum and hyperplastic sebaceous glands is a genetic mutant for the study of many pharmacological aspects especially human acne. Through this model, we examined the effects of several phospholipids on the secretion of sebum after topical application. The phospholipid derivatives were phosphatidylcholine (PC), hydrogenated phosphatidylcholine (HPC), phosphati dylserine (PS) and hydrogenated phosphatidylserine(HPS). All agents were dissolved into the vehicle (1, 3-Butanediol, ethanol and water) at 0.5％ weight volume and applied on the dorsal area of the fuzzy rat. To observe histological changes, the skin biopsies were stained with Oil Red O and the size and morphology of sebaceous gland was observed under microscope. Topical treatment with PC and/or HPC showed a marked decrease in sebum excretion. Especially hydrogenated PC (HPC) appeared to have more predominant sebosuppressive function than any other treatment. The other agents such as PS and HPS showed a marginal effect on sebum secretion. With the sebosuppressive activity, HPC and PC seem to have a good potential application on acne treatment. In order to obtain more insights into possible mechanisms behind the above observations, effects of each phospholipid on the expression of peroxisome proliferator-activated receptor (PPAR) genes were investigated. Recently, it has been demonstrated that expression and activation of PPAR subtypes appear to modulate the accumulation of cytoplasmic fat droplets that characterizes the sebocyte differentiation(1). It was also previously suggested that PPAR${\gamma}$ antagonist would seem possible to interfere sebum production without side effects (2). In this study we examined the diverse effects of the tested phospholipids on the expression of several PPAR genes based on reverse transcription-polymerase chain reaction (RT-PCR) from the topically treated skin of fuzzy rats. The results and possible implications are discussed.

• Journal of Preventive Medicine and Public Health
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• v.35 no.3
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• pp.245-254
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• 2002

Objective : To test if the intake of $H_2$ receptor antagonists ($H_2$-RAs) increases the risk of gastric cancer in the elderly. Methods : The source population for this study was drawn from the responders to a questionnaire survey administered to the Korea Elderly Pharmacoepidemiological Cohort (KEPEC), who were beneficiaries of the Korean Medical Insurance Corporation, were at least 65 years old, and residing in Busan in 1999. The information on $H_2$-RAs exposure was obtained from a drug prescription database compiled between inn. 1993 and Dec. 1994. The cases consisted of 76 gastric cancer patients, as confirmed from the KMIC claims data, the National Cancer Registry and the Busan Cancer Registry. The follow-up period was from Jan. 1993 to Dec. 1998. Cancer free controls were randomly selected by 1:4 individual matching, which took in to consideration the year of birth and gender. Information on confounders was collected by a mail questionnaire survey. The odds ratios, and their 95% confidence intervals, were calculated using a conditional logistic regression model. Results : After adjusting for a history of gastric ulcer symptoms, medication history, and body mass index, the adjusted OR (aOR) was 4.6 (95% CI=1.72-12.49). The odds ratio of long term use (more than 7 days) was 2.3 (95% CI=1.07-4.82). The odds ratio of short term use was 4.6 (95% CI=1.26-16.50). The odds ratio of parenteral use was 4.4 195% CI=1.16-17.05) and combination use between the oral and parenteral routes (aOR, 16.8; 95% CI=1.21-233.24) had the high risk of gastric cancer. The aOR of cimetidine was 1.7 (95% CI=1.04-2.95). The aOR of ranitidine was 2.0 (95% CI=1.21-3.40). The aOR of famotidine was 1.7 (95% CI=0.98-2.80). Conclusion : The intake of $H_2$-RAs might increase the risk of gastric cancer through achlorhydria in the elderly.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1995.04a
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• pp.88-88
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• 1995

Tetrahydroisoquinoline (THI) compounds have various pharmacological actions in the cardiovascular system. Recently, we have synthesized 1-${\alpha}$-naphthylmethyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline, YS 49. In the present study, we evaluated the effect of YS-49 on positive inotropic and chronotropic action using isolated rat heart and on blood pressure and heart rate using anesthesized rabbit. Vasodilating action was also assessed in isolated rat thoracic aorta. YS 49, concentration-dependently relaxed rat aorta precontracted with phenylephrine (PE, 0.3 ${\mu}$M) and high potassium (high K$\^$+/, 65.4 mM). The 50% inhibitory concentration (IC$\sub$50/) of YS 49 in PE-induced and high K$\^$+/-induded contraction was 5.36 ${\mu}$M and 2.52 ${\mu}$M, respectively. In isolated rat atria, YS 49 increased both heart rate and force, and in anesthesized rabbit it decreased blood pressure but increased heart rate. In addition, to know the mechanism of action of the compound, propranolol, nonselective ${\beta}$-antagonist, and phentolamine, ${\alpha}$-blocker, were used. Furthermore, a comparison with the effect of higenamine, trimetoquinol on the vasodilating action in rat thoracic aorta was also made. The action of YS 49 was inhibited by the presence of propranolo, not pentolamine. These results indicate that cardiotonic and vasodilatory action of YS 49 is attributable, at least in part, for ${\beta}$-receptor stimulation.