• Tuberculosis and Respiratory Diseases
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• v.44 no.1
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• pp.183-190
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• 1997

Tocolytics are agents widely used in the treatment of premature labor to inhibit uterine contractions. Ritodrine is most commonly used tocolytic agent and acts by increasing intracellular cyclic adenosine monophosphate, which decreases the activity of myosin light-chain kinase, the rate-limiting enzyme in the signal network leading to contraction. Physiologic effects associated with the use of ritodrine are due to their effect on bera-l as well as beta-2 receptors. Some of maternal complications of therapy are rachycardia, hyperglycemia, hypokalemia, lactic acidosis, myocardial ischemia, and pulmonary edema. Tocolytics induced pulmonary edema is a serious complication that can lead to marternal death, although infrequent, The incidence varies from 0.5% to 5% of those receiving these agents. Predisposing factors include the concommitant use of corticosteroid, twin gestation, fluid overload (particularly with saline), and anemia. Several mechanisms have been postulated, but the pathogenesis is uncertain. It is suggested that both types of mechanism, hydrostatic and permeability induced, might be involved. The association of tocolytic therapy with pulmonary edema appears to be unique to the pregnant state, because this complication has never been reported in asthmatic patients exposed to high dosages. We report a case of tocolytic induced pulmonary edema developed in 24 hours after delivery.

• IMMUNE NETWORK
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• v.7 no.1
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• pp.39-47
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• 2007

Background: Stromal cell-derived factor (SDF)-1 is a potent chemoattractant for activated T cells into the inflamed Rheumatoid arthritis (RA) synovium. To determine the effect of macrophage migration inhibitory factor (MIF) on the production of SDF-1 in the inflamed RA synovium. Methods: The expression of SDF-1 and MIF in RA and Osteoarthritis (OA) synovium was examined by immunohistochemical staining. The SDF-1 was quantified by RT-PCR and ELISA after RA fibroblast like synoviocyte (FLS) were treated with MIF in the presence and absence of inhibitors of intracellular signal molecules. The synovial fluid (SF) and serum levels of MIF and SDF-1 in RA, OA and healthy control were measured by ELISA. Results: Expression of SDF-1 and MIF in synovium was higher in RA patients than in OA patients. The production of SDF-1 was enhanced in RA FLS by MIF stimulation. Such effect of MIF was blocked by the inhibitors of NF-${\kappa}B$. Concentrations of SDF-1 in the serum and SF were higher in RA patients than in OA patients and healthy control. SDF-1 and MIF was overexpressed in RA FLS, and MIF could up-regulate the production of SDF-1 in RA FLS via NF-${\kappa}B$-mediated pathways. Conclusion: These results suggest that an inhibition of interaction between MIF from T cells and SDF-1 of FLS may provide a new therapeutic approach in the treatment of RA.

• Tuberculosis and Respiratory Diseases
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• v.79 no.4
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• pp.257-266
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• 2016

Background: Idiopathic pulmonary fibrosis is a common interstitial lung disease; it is a chronic, progressive, and fatal lung disease of unknown etiology. Over the last two decades, knowledge about the underlying mechanisms of pulmonary fibrosis has improved markedly and facilitated the identification of potential targets for novel therapies. However, despite the large number of antifibrotic drugs being described in experimental pre-clinical studies, the translation of these findings into clinical practices has not been accomplished yet. NADH:quinone oxidoreductase 1 (NQO1) is a homodimeric enzyme that catalyzes the oxidation of NADH to $NAD^+$ by various quinones and thereby elevates the intracellular $NAD^+$ levels. In this study, we examined the effect of increase in cellular $NAD^+$ levels on bleomycin-induced lung fibrosis in mice. Methods: C57BL/6 mice were treated with intratracheal instillation of bleomycin. The mice were orally administered with ${\beta}$-lapachone from 3 days before exposure to bleomycin to 1-3 weeks after exposure to bleomycin. Bronchoalveolar lavage fluid (BALF) was collected for analyzing the infiltration of immune cells. In vitro, A549 cells were treated with transforming growth factor ${\beta}1$ (TGF-${\beta}1$) and ${\beta}$-lapachone to analyze the extracellular matrix (ECM) and epithelial-mesenchymal transition (EMT). Results: ${\beta}$-Lapachone strongly attenuated bleomycin-induced lung inflammation and fibrosis, characterized by histological staining, infiltrated immune cells in BALF, inflammatory cytokines, fibrotic score, and TGF-${\beta}1$, ${\alpha}$-smooth muscle actin accumulation. In addition, ${\beta}$-lapachone showed a protective role in TGF-${\beta}1$-induced ECM expression and EMT in A549 cells. Conclusion: Our results suggest that ${\beta}$-lapachone can protect against bleomycin-induced lung inflammation and fibrosis in mice and TGF-${\beta}1$-induced EMT in vitro, by elevating the $NAD^+$/NADH ratio through NQO1 activation.

• The Korean Journal of Physiology and Pharmacology
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• v.18 no.2
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• pp.89-94
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• 2014

DA-6034, a eupatilin derivative of flavonoid, has shown potent effects on the protection of gastric mucosa and induced the increases in fluid and glycoprotein secretion in human and rat corneal and conjunctival cells, suggesting that it might be considered as a drug for the treatment of dry eye. However, whether DA-6034 induces $Ca^{2+}$ signaling and its underlying mechanism in epithelial cells are not known. In the present study, we investigated the mechanism for actions of DA-6034 in $Ca^{2+}$ signaling pathways of the epithelial cells (conjunctival and corneal cells) from human donor eyes and mouse salivary gland epithelial cells. DA-6034 activated $Ca^{2+}$-activated $Cl^-$ channels (CaCCs) and increased intracellular calcium concentrations ($[Ca^{2+}]_i$) in primary cultured human conjunctival cells. DA-6034 also increased $[Ca^{2+}]_i$ in mouse salivary gland cells and human corneal epithelial cells. $[Ca^{2+}]_i$ increase of DA-6034 was dependent on the $Ca^{2+}$ entry from extracellular and $Ca^{2+}$ release from internal $Ca^{2+}$ stores. Interestingly, these effects of DA-6034 were related to ryanodine receptors (RyRs) but not phospholipase C/inositol 1,4,5-triphosphate ($IP_3$) pathway and lysosomal $Ca^{2+}$ stores. These results suggest that DA-6034 induces $Ca^{2+}$ signaling via extracellular $Ca^{2+}$ entry and RyRs-sensitive $Ca^{2+}$ release from internal $Ca^{2+}$ stores in epithelial cells.

• Korean Journal of Veterinary Research
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• v.47 no.4
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• pp.363-370
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• 2007

Mongolian gerbil (Meriones unguiculatus) has been as an model animal for studing the neurological disease such as stroke and epilepsy because of the congenital incompleteries in Willis circle, as well as the investigation of water metabolism because of the long time-survival in the condition of water-deprived desert condition, compared with other species animal. Aquaporin 2 (AQP2) expressed at the surface of principal cells in collecting duct results from an equilibrium between the AQP2 in intracellular vesicles and the AQP2 on the plasma membrane. Aquaporin 4 (AQP4), which is expressed in cell in a wide range of organ, is also present in the collecting duct principal cells where this is abundant in the basolateral plasma membranes and represent potential exit pathways from the cell for water entering via AQP2. In this research, we divide 3 groups of which each group include the 5 animals. In the study of 7 or 14 days water restricted condition, we investigated the AQP2 and AQP4 by using a quantitative immunohistochemistry in the kidney. The results obtained in this study were summarized as followings. AQP2 is abundant in the apical plasma membrane and apical vesicles in the collecting duct principal cell and at rare abundance in connecting tubules. In the water-deprived Mongolian gerbil kidney, expression of AQP2 was continuosly increased in the cortical collecting duct and inner medullary collecting duct. This increase was both the apical region and cytoplasm. AQP4 is mainly expressed in the inner medulla, although some expression is also noted in the more proximal segment. In the water-deprived Mongolian gerbil kidney, AQP4 was also increased in the inner medullary collecting duct. Immunoactivity was increased in entire inner medullary collecting duct and newly detected in cytoplasm of principal cell. These findings suggest that increased levels of AQP2 and AQP4 in the cortical and inner medulalry collecting duct may play a important role for maintain fluid balance in the water-deprived kidney.

• The Korea Journal of Herbology
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• v.31 no.5
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• pp.71-78
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• 2016

Objectives : Diabetic nephropathy is one of the most common chronic complications of diabetes and a leading cause of end-stage renal failure in the world. Mesangial cell proliferation is known as the major pathologic features such as glomerulosclerosis and renal fibrosis. Wiryeongtang (WRT) is a well-known traditional herbal formula as therapeutic agents for chronic edema and dysuresia of renal homeostasis. In the present study, we investigated whether WRT inhibits high glucose (HG)-induced renal dysfunction by TGF-β/Smads signal regulation in cultured mesangial cells.Methods : Inhibitory effect of WRT (10-50 ㎍/ml) on HG-stimulated mesangial cells proliferation and dysfunction were evaluated by [³H]-thymidine incorporation, Western blot, and RT-qPCR.Results : WRT significantly decreased HG-accelerated thymidine incorporation in human renal mesangial cell in a dose-dependent levels. WRT induced down-regulation of cyclins/CDKs and up-regulation of CDK inhibitor, p21waf1/cip1 and p27kip1 expression. In addition, HG enhanced expression of dysfunction biomarker such as collagen IV and CTGF, which was markedly attenuated by WRT. WRT decreased TGF-β1 and Smad-2/Smad-4 expression, whereas increased Smad-7 expression under HG. Furthermore, WRT inhibited HG-induced inflammatory factors level such as ICAM-1 and MCP-1 as well as NF-κB p65 nuclear translocation and intracellular ROS production.Conclusions : These results suggested that WRT may alleviate mesangial proliferation and inflammation possibly involved in renal fibrotic process, further diabetic nephropathy through disturbing TGF-β1/Smad signaling and NF-κB/ROS pathway. Thus, WRT might prove to be effective in the treatment of renal dysfunction leading to diabetic nephropathy.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.34 no.4
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• pp.1-11
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• 2021

Objectives : The aim of this study was to investigated the anti-aging and anti-wrinkles effects of the pinus koreaiensis seed(PKS) oil. Methods : The anti-oxidant effect was performed by beta-carotene bleaching assay and the intracellular proteome was analyzed expression of each 15 proteins by 2-D electrophoresis. And fatty acid was analysed by gas chromatography. Anti-wrinkle effect was analyzing human skin by the PRIMOS system. Results : Fatty acid analysis of PKS oil has shown oleic acid was 49.7% and linoleic acid was 34.1%. And the antioxidant effect was about 125% compared with alpha-tocoperol(0.1%) by beta carotene bleaching assay. In 2D PAGE analysis, fifteen protein changes in five mechanisms which was collagen synthesis pathway, MMPs, ECM-cell interaction, cytokine, antioxidant enzymes were analyzed. In case of anti-wrinkle effect was proved in vivo by analyzing human skin by the PRIMOS system. The analysis results of eye wrinkles for 4 weeks showed an improvement effect of over 6%. Conclusions : In this study, the amount of protein change in the five mechanism through the cell experiment and the skin anti wrinkle efficacy by the human in vivo test were investigated. As a result pinus koreaiensis seed oil by supercritical extraction could be used as a anti-aging and anti-wrinkle substance for the skin.

• Tuberculosis and Respiratory Diseases
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• v.53 no.1
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• pp.36-45
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• 2002

Background : In mammals, the activity of antioxidant enzymes is increased in adult lung to adapt to hyperoxia. The increase of these activities is augmented in neonates and is known as an important mechanism of tolerance to high oxygen levels. Peroxiredoxin(Prx) is an abundant and ubiquitous intracellular antioxidant enzyme. Prx I and II are major cytosolic subtypes. The aim of this study was to examine th Prx I and II mRNA and protein expression levels in adult rat lungs and to compare then with those of neonatal rat lungs exposed to hyperoxia. Materials and Methods : Adult Sprague-Dawley rats and neonates that were delivered from timed pregnant Sprague-Dawley rat were randomly exposed to normoxia or hyperoxia. After exposure to high oxygen level for a set time, the bronchoalveolar lavage fluid and lung tissue were obtained. The Prx I and II protein expression levels were measured by western blot analysis using polyclonal rabbit anti-Prx I or anti-Prx II antibodies and the relative expression of the Prx I and Prx II per Actin protein were obtained as an internal standard. The Prx I and II mRNA expression levels were measured by northernblot analysis using Prx I and Prx II-specific cDNA prepared from pCRPrx I and pCRPrx II, and the relative Prx I and Prx II expression levels per Actin mRNA were obtained as an internal standard. Results : Hyperoxia induced some peak increase in the Prx I mRNA levels after 24 hour in adult rats. Interestingly, hyperoxia induced a marked increase of Prx I mRNA 24 hour in neonatal rats. However, hyperoxia did not induce an alteration in the expression of Prx II mRNA in both the adult and neonatal rat lungs. Hyperoxia did not induce an alteration in the expression of the Prx I and Prx II protein in both the adult and neonatal rat lungs. Hyperoxia did not induce an alteration in the amount of Prx I and Prx II protein all the times in the bronchoalveolar fluid of adult rats. Conclusion : Prx I and II is differently regulated by hyperoxia in adult and neonatal rat lung at the transcriptional level. The prominent upregulation of Prx I mRNA in neonates compared to those in adults by hyperoxia may be another mechanism of resistance to high oxygen levels in neonate.

• Clinical and Experimental Pediatrics
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• v.49 no.5
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• pp.475-481
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• 2006

Purpose : As the prevalence of childhood obesity is increasing, hypertension, hyperlipidemia, insulin resistance and diabetes mellitus have become problems. High homocysteine levels and low vitamin $B_{12}$ supplementation are acknowledged to have a role in coronary artery disease, but there are few studies on homocysteine, insulin and vitamin $B_{12}$ levels in obese children. We aimed to study whether homocysteine, insulin, vitamin $B_{12}$, folic acid levels could have any difference and relation in obese children. Methods : The disease group consisted of 27 children from 8 to 11 years old, whose obesity index was over 130. The control group consisted of 30 healthy children of the same age group. Obesity index and body mass index were calculated by height and body weight of the children, and their systolic and diastolic blood pressures at resting state were checked. Total cholesterol, triglyceride, homocysteine, insulin, vitamin $B_{12}$, folic acid levels were studied after 10 hours of fasting. Intracellular fluid, extracellular fluid, protein, mineral, muscle mass, lean body fat, fat mass and fat percentages were checked by bioelectrical impedance. Results : Homocysteine levels were higher in obese children($8.1{\pm}2.1{\mu}mol/mL$ vs. $4.9{\pm}1.0{\mu}mol/mL$). Insulin levels were also higher in obese children($26.8{\pm}11.2{\mu}IU/mL$ vs. $12.5{\pm}5.24{\mu}IUl/mL$). Vitamin $B_{12}$ was lower in obese children($798.6{\pm}174.3pg/mL$ vs. $967.8{\pm}405.0pg/mL$). But there was not a difference in the folic acid levels between the two groups. In obese children, systolic blood pressure (r=0.535), triglyceride(r=0.517), total cholesterol(r=0.408), folic acid(r=0.408), vitamin $B_{12}$(r=0.338) and abdomoanl fat %(r=0.306) had a positive correlation. Conclusion : We found definite differences of insulin, homocysteine, and vitamin $B_{12}$ plasma levels in obese children, but we need more study to use those parameters as risk factors of metabolic syndrome in pediatric obese patients.

• Journal of Embryo Transfer
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• v.19 no.2
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• pp.89-99
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• 2004

Stretch-activated channels (SACs) responds to membrane stress with changes in open probability (Po). They play essential roles in regulation of cell volume and differentiation, vascular tone, and in hormonal secretion. SACs highly present in Xenopus oocytes and Ascidian oocytes are suggested to be involved in the regulation of pH and fluid transport to balance the osmotic pressure, but remain unclear in mammanlian oocytes. This study was investigated to find the presence of SACs in hamster oocytes and to examine their electrophysiological properties. To infer a role of SAC in relation to the development of early stage, we followed up to the stage of two-cell zygote with patch clamp techniques. Single channels were elicited by negative pressure (lower than ­15 cm$H_2O$). Interestingly, SACs were dependent on permeable cations such as $Na^+$ or $K^+$. As permeable cation removed from both sides across the membrane, SAC activity completely disappeared. When permeable cations present only in intracellular compartment, outward currents appeared at positive potentials. In contrast to this, inward currents occurred only at the negative voltage when permeable cation absent in cell interior. These result suggests that SAC carry cations through the nonselective cation channel (NSC channel). Taken together, we found that stretch activated channels present in hamster oocyte and the channel may carry cations through NSC channels. This stretch activated-NSC channels may play physiological role(s) in oocyte growth, maturation, fertilization and embryogenesis in fertilized oocytes to two-cell zygotes of hamster.