• BMB Reports
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• v.54 no.6
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• pp.311-316
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• 2021

Ethanol often causes critical health problems by altering the neuronal activities of the central and peripheral nerve systems. One of the cellular targets of ethanol is the plasma membrane proteins including ion channels and receptors. Recently, we reported that ethanol elevates membrane excitability in sympathetic neurons by inhibiting Kv7.2/7.3 channels in a cell type-specific manner. Even though our studies revealed that the inhibitory effects of ethanol on the Kv7.2/7.3 channel was diminished by the increase of plasma membrane phosphatidylinositol 4,5-bisphosphate (PI(4,5)P₂), the molecular mechanism of ethanol on Kv7.2/7.3 channel inhibition remains unclear. By investigating the kinetics of Kv7.2/7.3 current in high K⁺ solution, we found that ethanol inhibited Kv7.2/7.3 channels through a mechanism distinct from that of tetraethylammonium (TEA) which enters into the pore and blocks the gate of the channels. Using a non-stationary noise analysis (NSNA), we demonstrated that the inhibitory effect of ethanol is the result of reduction of open probability (P_O) of the Kv7.2/7.3 channel, but not of a single channel current (i) or channel number (N). Finally, ethanol selectively facilitated the kinetics of Kv7.2 current suppression by voltage-sensing phosphatase (VSP)-induced PI(4,5)P₂ depletion, while it slowed down Kv7.2 current recovery from the VSP-induced inhibition. Together our results suggest that ethanol regulates neuronal activity through the reduction of open probability and PI(4,5)P₂ sensitivity of Kv7.2/7.3 channels.

• Asian-Australasian Journal of Animal Sciences
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• v.13 no.7
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• pp.922-928
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• 2000

The effects of animal species and supplements on rumen fluid characteristics, plasma urea-N (PUN) concentration, plasma urea-N pool size, urea-N degradation in the gut and urea-N net flux (urea-N synthesis rate) were studied in goats and sheep, with some minor differences detected. The animals were fed either chopped rice straw ad libitum+200 g soybean meal (SBM), or chopped rice straw ad libitum+190 g soybean meal+300 g sago meal (SBM+SM) for 14 days. The supplements were isonitrogenous (80 g crude protein/animal/d). [$^{14}C$]-urea was used as the marker for urea metabolism studies. Two animals from each species were fed either supplement in a cross-over design in two periods. The results showed that rumen pH was significantly (p<0.001) lower in animals fed SBM+SM than those fed SBM supplement. The ammonia concentrations of rumen fluid were significantly (p<0.01) higher in sheep (382.9 mg N/L) than goats (363.1 mg N/L) when fed SBM supplement but lower (282.5 mg N/L) than that of goats (311.0 mg N/L) when fed SBM+SM supplement. Total VFA concentrations were significantly (p<0.05) higher in animals fed SBM+SM supplement than those fed SBM supplement. Goats had significantly (p<0.01) higher molar proportions of acetate (79.1, 77.7%, respectively) than sheep (75.8, 74.0%, respectively) in both supplements. The molar proportion of acetate was significantly (p<0.05) higher, while that of butyrate lower in animals fed SBM supplement than those fed SBM+SM supplement. In animals fed SBM supplement, the molar proportion of propionate was significantly (p<0.01) higher in sheep (18.0%) than in goats (15.6%), but in animals fed SBM+SM, the molar proportion of butyrate was significantly (p<0.01) higher (9.6%) in sheep than in goats (7.2%). Plasma urea-N concentration, plasma urea-N pool size, urea-N degradation in the gut, urea-N net flux and the fraction of urea-C from the blood entering the rumen were not significantly different between goats and sheep fed either supplement. However, PUN concentration was significantly (p<0.05) lower in animals fed SBM+SM supplement (average of 13.8 mg N/100 ml) than in those fed SBM supplement (average of 16.5 mg N/100 ml). The urea net flux was significantly (p<0.05) higher in goats (average of 14.5 g N/d) than sheep (average of 12.9 g N/d), and animals fed SBM supplement showed higher (average of 14.9 g N/d) urea net flux than animals fed SBM+SM supplement (average of 12.9 g N/d). A significant (p<0.05) positive correlation was observed between urea-N net flux and urea-N degradation; urea-N net flux and pool size; urea-N net flux and urea excretion in the urine; and PUN and rumen ammonia in goats. While in sheep, significant (p<0.05) positive correlation was observed between urea-N net flux and urea excretion in the urine; and PUN and rumen ammonia.

• The Korean Journal of Physiology and Pharmacology
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• v.19 no.2
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• pp.99-104
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• 2015

The aim of this study is to develop a physiologically based pharmacokinetic (PBPK) model in intra-abdominal infected rats, and extrapolate it to human to predict moxifloxacin pharmacokinetics profiles in various tissues in intra-abdominal infected human. 12 male rats with intra- abdominal infections, induced by Escherichia coli, received a single dose of 40 mg/kg body weight of moxifloxacin. Blood plasma was collected at 5, 10, 20, 30, 60, 120, 240, 480, 1440 min after drug injection. A PBPK model was developed in rats and extrapolated to human using GastroPlus software. The predictions were assessed by comparing predictions and observations. In the plasma concentration versus time profile of moxifloxcinin rats, $C_{max}$ was $11.151{\mu}g/mL$ at 5 min after the intravenous injection and $t_{1/2}$ was 2.936 h. Plasma concentration and kinetics in human were predicted and compared with observed datas. Moxifloxacin penetrated and accumulated with high concentrations in redmarrow, lung, skin, heart, liver, kidney, spleen, muscle tissues in human with intra-abdominal infection. The predicted tissue to plasma concentration ratios in abdominal viscera were between 1.1 and 2.2. When rat plasma concentrations were known, extrapolation of a PBPK model was a method to predict drug pharmacokinetics and penetration in human. Moxifloxacin has a good penetration into liver, kidney, spleen, as well as other tissues in intra-abdominal infected human. Close monitoring are necessary when using moxifloxacin due to its high concentration distribution. This pathological model extrapolation may provide reference to the PK/PD study of antibacterial agents.

• Journal of Pharmaceutical Investigation
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• v.28 no.4
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• pp.215-221
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• 1998

In order to elucidate the fraction of sulfoxidation in the over all in vivo metabolism of chlorpromazine (CPZ), the sulfoxidation of CPZ to chlorpromazine sulfoxide (CPZSO) was studied in rats. CPZ (10 mg/kg) and CPZSO (1 mg/kg) were injected into the rat femoral vein, respectively. And the pharmacokinetic parameters were obtained from the plasma concentration-time profiles of CPZ and CPZSO determined by the simultaneous analysis using high-performance liquid chromatography. It was supposed that these drugs were almost metabolized in vivo because the total excreted amounts of CPZ and CPZSO via urinary and biliary route were lower than 1.4% and 10.61% of the administered dose, respectively. And also, it was found that the fraction of systemic clearance of CPZ which formed CPZSO $(F_{mi})$ was 0.115. These results showed that CPZ was sulfoxized by 11.5% in rats and the residue would be metabolized via the other routes.

• Journal of Pharmaceutical Investigation
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• v.28 no.2
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• pp.73-80
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• 1998

In order to elucidate the effect of N-demethylation on the in vivo metabolite kinetics, especially hepatic first-pass effect of trimebutine(TMB), the N-demethylation of TMB to N-monodesmethyl trimebutine(N-TMB) was studied in rats. TMB(10 mg/kg) and N-TMB(10 mg/kg) were injected into the femoral and the portal vein, respectively. And the pharmacokinetic parameters were obtained from the plasma concentration-time profiles of TMB and N-TMB determined by the simultaneous analysis using high-performance liquid chromatography. It was supposed that these drugs were almost metabolized in vivo because the urinary and biliary excreated amounts of TMB and N-TMB were lower than 0.1% of the administered dose. According to the hepatic biotransformation model and metabolic pathways of TMB proposed, it was found that the fraction of systemic clearance of TMB which formed N-TMB in liver$(G_{mi})$ was 0.826, that of TMB which furnishes the available N-TMB to the systemic circulation$(F_{mi})$ was 0.083, and the absolute hepatic bioavailability of N-TMB formed trom TMB$(F_{mi.p})$ was 0.1. These results showed that TMB was suspected of the sequential hepatic first-pass metabolism and N-demethylated by 82.6%. Therefore, the residue would be hydrolyzed by the esterase in the liver. That is, the ability of N-demethylation of TMB was 4.75-fold larger than that of hydrolysis by the esterase in rats.

• Proceedings of the Korean Biophysical Society Conference
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• 2003.06a
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• pp.45-45
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• 2003

We isolated a novel ankyrin-repeat containing protein, rSIAP (rSlo Interacting Ankyrin-repeat Protein), as an interacting protein to the cytosolic domain of the alpha-subunit of rat large-conductance Ca$\^$2+/-activated K$\^$+/ channel (rSlo) by yeast two-hybrid screening. Affinity pull-down assay showed the direct and specific interaction between rSIAP and rSlo domain. The channel-binding proteins can be classified into several categories according to their functional effects on the channel proteins, i.e. signaling adaptors, scaffolding net, molecular tuners, molecular chaperones, etc. To obtain initial clues on its functional roles, we investigated the cellular localization of rSIAP using immunofluorescent staining. The results showed the possible co-localization of rSlo and rSIAP protein near the plasma membrane, when co-expressed in CHO cells. We then investigated the functional effects of rSIAP on the rSlo channel using electrophysiological means. The co-expression of rSIAP accelerated the activation of rSlo channel. These effects were initiated at the micromolar [Ca$\^$2+/]$\_$i/ and gradually increased as [Ca$\^$2+/]$\_$i/ raised. Interestingly, rSIAP decreased the inactivation kinetics of rSlo channel at micromolar [Ca$\^$2+/]$\_$i/, while the rate was accelerated at sub-micromolar [Ca$\^$2+/]$\_$i/. These results suggest that rSIAP may modulate the activity of native BK$\_$Ca/ channel by altering its gating kinetics depending on [Ca$\^$2+/]$\_$i/. To localize critical regions involved in protein-protein interaction between rSlo and rSIAP, a series of sub-domain constructs were generated. We are currently investigating sub-domain interaction using both of yeast two-hybrid method and in vitro binding assay.

• Proceedings of the Korean Vacuum Society Conference
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• 2012.08a
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• pp.270-270
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• 2012

Low temperature atmospheric pressure plasmas (APPs) have been known to be effective for living cell inactivation in the water [1]. Many earlier research found that pH level of the solution was changed from neutral to acidic after plasma treatment. The importance of the effect of acidity of the solution for cell treatments has already been reported by many experiments. In addition, several studies have demonstrated that the addition of a small amount of oxygen to pure helium results in higher sterilization efficiency of APPs [2]. However, it is not clear yet which species are key factors for the cell treatment. To find key factors, we used GMoo simulation. We elucidate the processes through which pH level in the solution is changed from neutral to acidic after plasma exposure and key components with pH and air variation with using GMoo simulation. First, pH level in a liquid solution is changed by He+ and He(21S) radicals. Second, O3 density decreases as pH level in the solution decreases and air concentration decreases. It can be a method of removing O3 that cause chest pain and damage lung tissue when the density is very high. H2O2, HO2 and NO radicals are found to be key factors for cell inactivation in the solution with pH and air variation.

• Journal of Welding and Joining
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• v.21 no.4
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• pp.46-55
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• 2003

TiO$_2$-WO$_3$(8.2wt%) coatings were prepared by the APS (Atmospheric Plasma Spraying) process to clarify the relationship between the process parameters(H$_2$ gas flow rate of plasma 2nd gas and spraying distance) of the APS coating and photo-decomposition efficiency kinetics of the MB(methylene blue) aqueous solution decomposition and to understand the effect of addition of WO$_3$ on photocatalytic properties of TiO$_2$ sprayed coating. Further, the temperature and velocity of flying particles were measured by DPV-2000 to investigate the relationship between microstructure of coatings and process parameters. Properties of coatins were investigated by XRD, SEM, XPS, RAMAN, UV/VIS spectrometer. In case of the TiO$_2$-WO$_3$(8.2wt%) coating, it had a lower anatase fraction than that of pure-TiO$_2$ coatings because of flying in the higher temperature plasma plume by the heavy weight of TiO$_2$, WO$_3$. And, when WO$_3$ added powders were spayed, the doping effects of W ions substituted into the Ti ion sites was not occured during melting and solidification cycles of spraying. It was found that the addition of WO$_3$ was ineffective effective on increasing photo-decomposition efficiency of TiO$_2$ sprayed coating.

• Polymer(Korea)
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• v.34 no.2
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• pp.89-96
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• 2010

Adhesive binders with core-shell structure of organic/organic pair were prepared by emulsion polymerization of acrylic monomers, such as methyl methacrylate(MMA), ethyl acrylate(EA), n-butyl acrylate(BA), and styrene(St). Ammonium persulfate (APS) was used as an water soluble initiator in the presence of an anionic surfactant, sodium dodecyl benzene sulfonate (SDBS). Non-woven fabric and leather were impregnated with the adhesive binder. The surface of the impregnated fabric and leather were treated with plasma technique and then kinetics analysis and mechanical properties were measured. The conversions of the polymerization of core-shell binder (MMA/EA, MMA/BA) were greater than 90%. When the core-shell binder was prepared at equimolar conditions, the increasing effect of the core-shell binder on the state peel strength of the impregnated and plasma-treated non-woven/non-woven fabric has the order of MMA/St, EA/BA, BA/MMA, EA/St, and EA/MMA. When the core-shell binder was prepared at non-equimolar conditions, the increasing effect of the core-shell binder on the state peel strength of the non-woven fabric/leather has the order of MMA/BA, BA/EA, MMA/EA, St/MMA, and EA/St.

• YAKHAK HOEJI
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• v.38 no.2
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• pp.123-130
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• 1994

Physicochemical properties and hydrolysis kinetics of new some oral cephalosporins were examined in buttered solution and human plasma or rat liver homogenate. The test cephalosporins were 7-[(Z)-2-(2-aminothiazole-4-yl)-2- methoxyiminoacetamido]-3-[4-(2-pyridyl)piperazinyl] thiocarbonylthhiomethyl-3-cephem-4-carboxylic acid (CEN1), 7-[(Z)-2-(2-aminoth iazole-4-yl)-2-methoxyiminoacetamido]-3-[4-(2-pyrimidyl)piperazinyl]th iocarbonylthiomethyl-3-cephem-4-carboxylic acid (CEN2), pivaloyloxymethyl-7-[ (Z)-2-(2-aminothiazole-4-yl)-2-methoxyiminoacetamido]-3-[4-(2-pyridyl)piperazi nyl]thiocarbonylthiomethy1-3-cephem-4-carboxylate (CEN1P), and pivaloyloxymethyl-7-[(Z)-2-(2-aminothiazole-4-yl)-2-methoxyiminoacetamido]-3-[ 4-(2-pyrimidyl)piperazinyl]thiocarbonyl-thiomethyl-3-cephem-4-carboxylate (CEN2P). The partition coefficient(Ko/w) of CEN1P, CEN2P were higher than those of CEN1, CEN2. The calculated pKa values of CEN1, CEN2, CEN1P, and CEN2P were 7.09, 7.75, 4.92, and 5.39, respectively. The hydrolysis of CEN1P and CEN2P were not depend on the composition of pH of the test medium except weak alkaline buffered solution (pH 8.00). CEN1 and CEN2 were very stable in pH 6.80 and 8.00 buffer solutions. CEN1P and CEN2P were rapidly deesterified to CEN1 and CEN2 in human plasma and in rat liver homogenate. Half-lives$(t_{1/2})$ of CEN1 and CEN2 were 3.49 and 4.93 hr in human plasma, 1.47 and 1.26 hr in rat liver homogenate, respectively.