• The Korean Journal of Physiology and Pharmacology
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• v.9 no.2
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• pp.103-108
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• 2005

To study the direct effect of somatostatin (SS) on calcium channel current ($I_{Ba}$) in guinea-pig gastric myocytes, $I_{Ba}$ was recorded by using whole-cell patch clamp technique in single smooth muscle cells. Nicardipine ($1{\mu}M$), a L-type $Ca^{2+}$ channel blocker, inhibited $I_{Ba}$ by $98{\pm}1.9$% (n=5), however $I_{Ba}$ was decreased in a reversible manner by application of SS. The peak $I_{Ba}$ at 0 mV were decreased to $95{\pm}1.5$, $92{\pm}1.9$, $82{\pm}4.0$, $66{\pm}5.8$, $10{\pm}2.9$% at $10^{-10}$, $10^{-9}$, $10^{-8}$, $10^{-7}$, $10^{-5}$ M of SS, respectively (n=3∼6; $mean{\pm}SEM$). The steady-state activation and inactivation curves of $I_{Ba}$ as a function of membrane potentials were well fitted by a Boltzmann equation. Voltage of half-activation ($V_{0.5}$) was $-12{\pm}0.5$ mV in control and $-11{\pm}1.9$ mV in SS treated groups (respectively, n=5). The same values of half-inactivation were $-35{\pm}1.4$ mV and $-35{\pm}1.9$ mV (respectively, n=5). There was no significant difference in activation and inactivation kinetics of $I_{Ba}$ by SS. Inhibitory effect of SS on $I_{Ba}$ was significantly reduced by either dialysis of intracellular solution with $GDP_{\beta}S$, a non-hydrolysable G protein inhibitor, or pretreatment with pertussis toxin (PTX). SS also decreased contraction of guinea-pig gastric antral smooth muscle. In conclusion, SS decreases voltage-dependent L-type calcium channel current ($VDCC_L$) via PTXsensitive signaling pathways in guinea-pig antral circular myocytes.

• The Korean Journal of Physiology and Pharmacology
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• v.17 no.5
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• pp.469-477
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• 2013

This study investigated effect of extract containing quercetin-3-O-${\beta}$-D-glucuronopyranoside from Rumex Aquaticus Herba (ECQ) against chronic gastritis in rats. To produce chronic gastritis, the animals received a daily intra-gastric administration of 0.1 ml of 0.15% iodoacetamide (IA) solution for 7 days. Daily exposure of the gastric mucosa to IA induced both gastric lesions and significant reductions of body weight and food and water intake. These reductions recovered with treatment with ECQ for 7 days. ECQ significantly inhibited the elevation of the malondialdehyde levels and myeloperoxidase activity, which were used as indices of lipid peroxidation and neutrophil infiltration. ECQ recovered the level of glutathione, activity of superoxide dismutase (SOD), and expression of SOD-2. The increased levels of total NO concentration and iNOS expression in the IA-induced chronic gastritis were significantly reduced by treatment with ECQ. These results suggest that the ECQ has a therapeutic effect on chronic gastritis in rats by inhibitory actions on neutrophil infiltration, lipid peroxidation and various steps of reactive oxygen species (ROS) generation.

• Journal of Korean Neurosurgical Society
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• v.51 no.6
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• pp.328-333
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• 2012

Objective : The aim of this study is to determine the association between the cerebrospinal fluid (CSF) biomarkers and inflammation, and the predictive value of these CSF biomarkers for subsequent shunt associated infection. Methods : We obtained CSF samples from the patients with hydrocephalus during ventriculoperitoneal (VP) shunt operations. Twenty-two patients were enrolled for this study and divided into 3 groups: subarachnoid hemorrhage (SAH)-induced hydrocephalus, idiopathic normal pressure hydrocephalus (INPH) and hydrocephalus with a subsequent shunt infection. We analyzed the transforming growth factor-${\beta}1$, tumor necrosis factor-${\alpha}$, vascular endothelial growth factor (VEGF) and total tau in the CSF by performing enzyme-linked immunosorbent assay. The subsequent development of shunt infection was confirmed by the clinical presentations, the CSF parameters and CSF culture from the shunt devices. Results : The mean VEGF concentration (${\pm}$standard deviation) in the CSF of the SAH-induced hydrocephalus, INPH and shunt infection groups was $236{\pm}138$, $237{\pm}80$ and $627{\pm}391$ pg/mL, respectively. There was a significant difference among the three groups (p=0.01). Between the SAH-induced hydrocephalus and infection groups and between the INPH and infection groups, there was a significant difference of the VEGF levels (p<0.01). However, the other marker levels did not differ among them. Conclusion : The present study showed that only the CSF VEGF levels are associated with the subsequent development of shunt infection. Our results suggest that increased CSF VEGF could provide a good condition for bacteria that are introduced at the time of surgery to grow in the brain, rather than reflecting a sequel of bacterial infection before VP shunt.

• Journal of Nutrition and Health
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• v.53 no.1
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• pp.1-12
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• 2020

Purpose: Diabetic nephropathy is one of the most important diabetic complications prompted by chronic hyperglycemia, characterized by glomerulosclerosis, tubular fibrosis, and it eventually causes kidney failure. Nobiletin is a polymethoxyflavone present in tangerine and other citrus peels, and has anti-cancer and anti-inflammatory effects. This study investigated the effects of nobiletin on glomerular fibrosis through inhibition of the transforming growth factor (TGF)-β1-Src-caveolin-1 pathway. Methods: Human renal mesangial cells (HRMC) were incubated in media containing 33 mM glucose with or without 1-20 uM nobiletin for 3 day. The cellular expression levels of fibrogenic collagen IV, fibronectin, connective tissue growth factor (CTGF), TGF-β1, Src and caveolin-1 were all examined. In addition, TGF-β1, Src and caveolin-1 proteins were screened to reveal the relationship among TGF-β1-Src-caveolin-1 signaling in glomerular fibrosis. Results: High glucose promoted the production of collagen IV, fibronectin and CTGF in HRMC, which was inhibited in a dose dependent manner by 1-20 uM nobiletin. The Western blot data showed that high glucose elevated the expression of TGF-β1, Src, caveolin-1 and Rho GTPase. When nobiletin was treated to the HRMC exposed to high glucose, the expression of TGF-β1-Src-caveolin-1 was dampened. Finally, TGF-β1-Src-caveolin-1 signaling pathway was activated in high glucose-exposed HRMC, and such activation was encumbered by nobiletin. Conclusion: These result demonstrated that nobiletin blunted high glucose-induced extracellular matrix accumulation via inhibition of the TGF-β1-Src-caveolin-1 related intracellular signaling pathway. Nobiletin may be a potent renoprotective agent to counteract diabetes-associated glomerular fibrosis that leads to kidney failure.

• Journal of Yeungnam Medical Science
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• v.10 no.1
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• pp.144-156
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• 1993

This study was performed to investigate the effect of octreotide on the contractility of rat vas deferens. The smooth muscle strips isolated from the prostatic portion were myographied in isolated organ bath, Electric field stimulation (monophasic square wave, duration: 1 mSec, voltage : 50 V, frequency : 5 Hz or 30 Hz, train: 10 Sec) produced reproducible contraction. The contraction was composed of two component, first phasic component (FPC) and second tonic component (STC). These contractions were abolished by tetrodotoxin ($1{\mu}M$). Octreotide inhibited the field stimulation induced contractions both FPC and STC concentration-dependently. The FPC was decreased by a desentization of purinergic receptor by pretreatment of mATP, and the STC was decreased by pretreatment of reserpine(3 mg/kg, IP) 24 hours before experiments. Octreotide reduced the field stimulation induced contraction in the presence of mATP and of reserpinized muscle strips. The inhibitory effect of octreotide was more potent at 5 Hz than at 30 Hz. Octreotide did not affect basal ton and exogenous norepinephrine- or ATP-induced contraction. These results suggest that octreotide inhibit the contractility of the isolated rat vas deferens by inhibition of the release of neurotransmitters, both ATP and norepinephrine from adrenergic nerve terminal.

• Asian-Australasian Journal of Animal Sciences
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• v.30 no.4
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• pp.462-469
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• 2017

Objective: The aim of this study is to identify genomic regions or genes controlling growth traits in pigs. Methods: Using a panel of 54,148 single nucleotide polymorphisms (SNPs), we performed a genome-wide Association (GWA) study in 562 pure Yorshire pigs with four growth traits: average daily gain from 30 kg to 100 kg or 115 kg, and days to 100 kg or 115 kg. Fixed and random model Circulating Probability Unification method was used to identify the associations between 54,148 SNPs and these four traits. SNP annotations were performed through the Sus scrofa data set from Ensembl. Bioinformatics analysis, including gene ontology analysis, pathway analysis and network analysis, was used to identify the candidate genes. Results: We detected 6 significant and 12 suggestive SNPs, and identified 9 candidate genes in close proximity to them (suppressor of glucose by autophagy [SOGA1], R-Spondin 2 [RSPO2], mitogen activated protein kinase kinase 6 [MAP2K6], phospholipase C beta 1 [PLCB1], rho GTPASE activating protein 24 [ARHGAP24], cytoplasmic polyadenylation element binding protein 4 [CPEB4], GLI family zinc finger 2 [GLI2], neuronal tyrosine-phosphorylated phosphoinositide-3-kinase adaptor 2 [NYAP2], and zinc finger protein multitype 2 [ZFPM2]). Gene ontology analysis and literature mining indicated that the candidate genes are involved in bone, muscle, fat, and lung development. Pathway analysis revealed that PLCB1 and MAP2K6 participate in the gonadotropin signaling pathway and suggests that these two genes contribute to growth at the onset of puberty. Conclusion: Our results provide new clues for understanding the genetic mechanisms underlying growth traits, and may help improve these traits in future breeding programs.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.6
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• pp.2251-2256
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• 2015

To study effects of cellular FLICE (FADD-like IL-$1{\beta}$-converting enzyme)-inhibitory protein (c-FLIP) inhibition by RNA interference (RNAi) on sensitivity of U2OS cells to tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL)-induced apoptosis, plasmid pSUPER-c-FLIP-siRNA was constructed and then transfected into U2OS cells. A stable transfection cell clone U2OS/pSUPER-c-FLIP-siRNA was screened from the c-FLIP-siRNA transfected cells. RT-PCR and Western blotting were applied to measure the expression of c-FLIP at the levels of mRNA and protein. The results indicated that the expression of c-FLIP was significantly suppressed by the c-FLIP-siRNA in the cloned U2OS/pSUPER-c-FLIP-siRNA as compared with the control cells of U2OS/pSUPER. The cloned cell line of U2OS/pSUPER-c-FLIP-siRNA was further examined for TRAILinduced cell death and apoptosis in the presence of a pan-antagonist of inhibitor of apoptosis proteins (IAPs) AT406, with or without 4 hrs pretreatment with rocaglamide, an inhibitor of c-FLIP biosynthesis, for 24 hrs. Cell death effects and apoptosis were measured by the methods of MTT assay with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and flow cytometry, respectively. The results indicated that TRAIL-induced cell death in U2OS/pSUPER-c-FLIP-siRNA was increased compared with control cells U2OS/pSUPER in the presence or absence of AT406. Flow cytometry indicated that TRAIL-induced cell death effects proceeded through cell apoptosis pathway. However, in the presence of rocaglamide, cell death or apoptotic effects of TRAIL were similar and profound in both cell lines, suggesting that the mechanism of action for both c-FLIP-siRNA and rocaglamide was identical. We conclude that the inhibition of c-FLIP by either c-FLIP-siRNA or rocaglamide can enhance the sensitivity of U2OS to TRAIL-induced apopotosis, suggesting that inhibition of c-FLIP is a good target for anti-cancer therapy.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.6
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• pp.2629-2633
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• 2012

Background: Raw betel nut (RBN) chewing is an important contributing factor for esophageal squamous cell carcinoma (ESCC), although associated genomic changes remain unclear. One difficulty in assessing the effects of exclusively RBN induced genetic alterations has been that earlier studies were performed with samples of patients commonly using tobacco and alcohol, in addition to betel-quid. Both CDKN2A (at 9p21) and Rb1 gene (at 13q14.2) are regarded as tumor suppressors involved in the development of ESCC. Therefore, the present study aimed to verify the RBN's ability to induce ESCC and assess the involvement of CDKN2A and Rb1 genes. Methods: A panel of dinucelotide polymorphic markers were chosen for loss of heterozygosity studies in 93 samples of which 34 were collected from patients with only RBN-chewing habit. Promoter hypermethylation was also investigated. Results: Loss in microsatellite markers D9S1748 and D9S1749, located close to exon $1{\beta}$ of CDKN2A/ARF gene at 9p21, was noted in 40% ESCC samples with the habit of RBN-chewing alone. Involvement of a novel site in the 9p23 region was also observed. Promoter hypermethylation of CDKN2A gene in the samples with the habit of only RBN-chewing alone was significantly higher (p=0.01) than Rb1 gene, also from the samples having the habit of use both RBN and tobacco (p=0.047). Conclusions: The data indicate that the disruption of 9p21 where CDKN2A gene resides, is the most frequent critical genetic event in RBN-associated carcinogenesis. The involvement of 9p23 as well as 13q14.2 could be required in later stages in RBN-mediated carcinogenesis.

• Journal of Pharmaceutical Investigation
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• v.28 no.3
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• pp.185-191
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• 1998

A bioequivalence study of the Loxipen tablets (Dae Wha Pharmaceutical Co., Korea) to the Loxonin tablets (Dong Hwa Pharmaceutical Co., Korea), formulations of sodium loxoprofen anhydrous 60 mg, was conducted. Sixteen healthy Korean male subjects received each formulation at the dose of 60 mg as sodium loxoprofen anhydrous in a $2{\times}2$ crossover study. There was a 2-week washout period between the dose. Plasma concentrations of loxoprofen were monitored by an HPLC method for over a period of 6 h after each administration. AUC (area under the plasma concentration-time curve from time zero to infinity) was calculated by the linear trapezoidal and extrapolation method. $C_{max}$ (maximum plasma drug concentration) and $T_{max}$ $(time\;to\;reach\;C_{max})$ were compiled from the plasma drug concentration-time data. Analysis of variance (ANOVA) revealed that there are no differences in AUC, $C_{max}$ and $T_{max}$ between the formulations. The apparent differences between the formulations in these parameters were all far less than 20% (i.e., 5.88, 7.81 and 6.09% for AUC, $C_{max}$ and $T_{max}$, respectively). Minimum detectable differences (%) at ${\alpha}=0.1$ and $1-{\beta}=0.8$ were all less than 20% difference in these parameters between the formulations were all over 0.8 (i.e., 15.81, 13.13 and 19.85 for AUC, $C_{max}$ and $T_{max}$, respectively). The 90% confidence intervals for these parameters were also within ${\pm}20%$ (i.e., $-16.52{\sim}4.77$, $-16.65{\sim}1,02$ and $-19.45{\sim}7.28%$ for AUC, $C_{max}$ and $T_{max}$, respectively). These results satisfy the bioequivalence criteria of the Korea Food and Drug Administration (KFDA) guidelines (No. 98-51). Therefore, these results indicate that the 2 formulations of loxoprofen are bioequivalent and, thus, may be prescribed interchangeably.

• Journal of Microbiology and Biotechnology
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• v.27 no.6
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• pp.1138-1149
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• 2017

The use of microalgal biomass is an interesting technology for the removal of heavy metals from aqueous solutions owing to its high metal-binding capacity, but the interactions with bacteria as a strategy for the removal of toxic metals have been poorly studied. The goal of the current research was to investigate the potential of Burkholderia tropica co-immobilized with Chlorella sp. in polyurethane discs for the biosorption of Hg(II) from aqueous solutions and to evaluate the influence of different Hg(II) concentrations (0.041, 1.0, and 10 mg/l) and their exposure to different contact times corresponding to intervals of 1, 2, 4, 8, 16, and 32 h. As expected, microalgal bacterial biomass adhered and grew to form a biofilm on the support. The biosorption data followed pseudo-second-order kinetics, and the adsorption equilibrium was well described by either Langmuir or Freundlich adsorption isotherm, reaching equilibrium from 1 h. In both bacterial and microalgal immobilization systems in the co-immobilization of Chlorella sp. and B. tropica to different concentrations of Hg(II), the kinetics of biosorption of Hg(II) was significantly higher before 60 min of contact time. The highest percentage of biosorption of Hg(II) achieved in the co-immobilization system was 95% at pH 6.4, at 3.6 g of biosorbent, $30{\pm}1^{\circ}C$, and a mercury concentration of 1 mg/l before 60 min of contact time. This study showed that co-immobilization with B. tropica has synergistic effects on biosorption of Hg(II) ions and merits consideration in the design of future strategies for the removal of toxic metals.