• Journal of Ginseng Research
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• v.44 no.2
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• pp.258-266
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• 2020

Background: Oxidative stress-induced cardiomyocytes apoptosis is a key pathological process in ischemic heart disease. Glutathione reductase (GR) reduces glutathione disulfide to glutathione (GSH) to alleviate oxidative stress. Ginsenoside Rb1 (GRb1) prevents the apoptosis of cardiomyocytes; however, the role of GR in this process is unclear. Therefore, the effects of GRb1 on GR were investigated in this study. Methods: The antiapoptotic effects of GRb1 were evaluated in H9C2 cells by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, annexin V/propidium iodide staining, and Western blotting. The antioxidative effects were measured by a reactive oxygen species assay, and GSH levels and GR activity were examined in the presence and absence of the GR inhibitor 1,3-bis-(2-chloroethyl)-1-nitrosourea. Molecular docking and molecular dynamics simulations were used to investigate the binding of GRb1 to GR. The direct influence of GRb1 on GR was confirmed by recombinant human GR protein. Results: GRb1 pretreatment caused dose-dependent inhibition of tert-butyl hydroperoxide-induced cell apoptosis, at a level comparable to that of the positive control N-acetyl-L-cysteine. The binding energy between GRb1 and GR was positive (-6.426 kcal/mol), and the binding was stable. GRb1 significantl reduced reactive oxygen species production and increased GSH level and GR activity without altering GR protein expression in H9C2 cells. Moreover, GRb1 enhanced the recombinant human GR protein activity in vitro, with a half-maximal effective concentration of ≈2.317 μM. Conversely, 1,3-bis-(2-chloroethyl)-1-nitrosourea co-treatment significantly abolished the GRb1's apoptotic and antioxidative effects of GRb1 in H9C2 cells. Conclusion: GRb1 is a potential natural GR agonist that protects against oxidative stress-induced apoptosis of H9C2 cells.

• Archives of Pharmacal Research
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• v.28 no.4
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• pp.413-420
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• 2005

We previously demonstrated the ability of ginseng saponins (active ingredients of Panax ginseng) to enhance $Ca^{2+}$-activated $Cl^{-}$ current. The mechanism for this ginseng saponin-induced enhancement was proposed to be the release of $Ca^{2+}$ from $IP_{3}-sensitive$ intracellular stores through the activation of PTX-insensitive $G\alpha_{q/11}$ proteins and PLC pathway. Recent studies have shown that calmodulin (CaM) regulates $IP_{3}$ receptor-mediated $Ca^{2+}$ release in both $Ca^{2+}-dependent$ and -independent manner. In the present study, we have investigated the effects of CaM on ginseng saponin-induced $Ca^{2+}$-activated $Cl^{-}$ current responses in Xenopus oocytes. Intraoocyte injection of CaM inhibited ginseng saponin-induced $Ca^{2+}$-activated $Cl^{-}$ current enhancement, whereas co-injection of calmidazolium, a CaM antagonist, with CaM blocked CaM action. The inhibitory effect of CaM on ginseng saponin-induced $Ca^{2+}$-activated $Cl^{-}$ current enhancement was dose- and time-dependent, with an $IC_{50} of 14.9\pm3.5 {\mu}M$. The inhibitory effect of CaM on saponin's activity was maximal after 6 h of intraoocyte injection of CaM, and after 48 h the activity of saponin recovered to control level. The half-recovery time was calculated to be $16.7\pm4.3 h$. Intraoocyte injection of CaM inhibited $Ca^{2+}$-induced $Ca^{2+}$-activated $Cl^{-}$ current enhancement and also attenuated $IP_{3}$-induced $Ca^{2+}$-activated $Cl^{-}$ current enhancement. $Ca^{2+}$/CaM kinase II inhibitor did not inhibit CaM-caused attenuation of ginseng saponin-induced $Ca^{2+}$-activated $Cl^{-}$ current enhancement. These results suggest that CaM regulates ginseng saponin effect on $Ca^{2+}$-activated $Cl^{-}$ current enhancement via $Ca^{2+}$-independent manner.

• Korean Journal of Clinical Pharmacy
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• v.12 no.2
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• pp.71-75
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• 2002

This study was carried out to compare the bioavailability of $Ceclex^{(R)}$ (test drug, cefaclor 250 mg/capsule) with that of $Ceclor^{(R)}$ (reference drug) and to estimate the pharmacokinetic parameters of cefaclor in healthy Korean adult. The bioavailability was examined on 20 healthy volunteers who received a single dose (250 mg) of each drug in the fasting state in a randomized balanced 2-way crossover design. After dosing, blood samples were collected for a period of 6hours. Plasma concentrations of cefaclor were determined using HPLC with UV detection. The pharmacokinetic parameters $(AUC_{0-6hr},\;C_{max},\;T_{max},\;AUC_{int},\;K_e,\;t_{1/2},\;Vd)$ F, and CL/F) were calculated with non-compartmental pharmacokinetic analysis. The ANOVA test was utilized for the statistical analysis of the $T_{max},\;log-transformed\;AUC_{0-6hr}\;log-transformed\;C_{max},\;t_{l/2},\;V_d/F$, and CL/F. The ratios of geometric means of AUC0-6hr and $C_{max}$ between test drug and reference drug were $103.2\%\;(6.74\;{\mu}g{\cdot}hr/ml\;vs\;6.53{\pm}g{\cdot}hr/ml)\;and\;100.4\%\;(4.85\;{\mu}g\ml\;vs\;4.82\;{\mu}g/ml)$, respectively. The $T_{max}$ of test drug and reference drug were $0.9\pm0.38\;hr\;and\;0.83\pm0.34$ hrs, respectively. The $90\%$ confidence intervals of mean difference of logarithmic transformed $AUC_{0-6h},\;and\;C_{max}$ were log $0.98{\sim}log$ 1.08 and log $0.88{\sim}log1.15$, respectively. It shows that the bioavailability of test drug is equivalent with that of reference drug. The estimated half-life of this study was longer $(1.21\pm0.27\;hrs\;vs\;0.5-1\;hr)$, the Vd/F was larger $(68.89\pm25.72L$ vs 24.9L), and the CL/F was higher $(38.62\pm7.09\;L/hr$ vs 24.9 L/hr) than the previously reported values.

• Journal of Biomedical Engineering Research
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• v.18 no.3
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• pp.291-299
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• 1997

As a microimaging device detecting gamma rays emitted from small lesions or tumors during operation, the intraoperative surgical probe has been proposed and is now under development. We have designed a multipurpose portable gamma prove system and evaluated the performance both for the absolute counting purpose of residual radioactivities and for the localizing capability of gamma events using the NaI(Tl) crystal and two types of photomultiplier tubes(PMTs). Counting efficiencies in the range of routine clinical use of radiation dose were measured using the assembly of single channel PMTs and 0.5 inch thick NaI(Tl) crystal of 1 inch diameter. The positioning of gamma events for imaging purpose requires the multiple channel PMTs with appropriate positioning electronics. We have designed a simple and reliable positioning circuit based on the concept of modified Anger. In preliminary experiments using the multiple channel PMT of 3 inch diameter and the dim lighth source, we were able to trace and localize the correct position with reduced positioning error by the use of two multiplier/divider chipset and simplified peripherals. The energy resolutions for the counting gamma probe measured as full width at half maximum(FWHM) for Cs-137, F-18, Tc-99m were 12%, 13%, and 36%, respectively. The spatial resolution for the imaging gamma probe measured as FWHM for green LED was 2.9 mm. The results indicate that the currently developing probe is very promising and could be very useful for many applications in nuclear medicine. Future studies will include developing collimators, improving interface hardwares, and evaluating the system with clinical data.

• Journal of Pharmaceutical Investigation
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• v.37 no.6
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• pp.397-402
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• 2007

To evaluate the bioequivalence of two venlafaxine formulations, a standard 2-way randomized cross-over study was conducted in twenty-four healthy male Korean volunteers. A single oral dose of 75 mg of test formulation Venfaxine $OR^{(R)}$ (tablet) or reference formulation Efexor $XR^{(R)}$ (capsule) was administered with one-week washout period. Plasma concentrations of venlafaxine were assayed for over a period of 72 hours with a well validated method using liquid chromatography coupled to tandem mass spectrometry (LC-MS-MS). The $mean{\pm}S.D$. of maximum concentration $(C_{max})$ and elimination half-life $(t_{1/2})$ were $64.7{\pm}28.5$ ng/mL, $9.2{\pm}3.0$ h, and $67.2{\pm}30.2$ ng/mL, $9.9{\pm}3.5$ h for test and reference formulations, respectively. Time to reach maximum concentration $(T_{max})$ expressed in median value (range), for the test and the reference, were 10 h (6-14) and 8h (4-12), respectively. Similarly, area under the plasma concentration-time curve, from time zero to last sampling time $(AUC_t)$ and from time zero to time infinity $(AUC_{inf})$, for test and reference formulations were $1185{\pm}755$, $1326{\pm}896$ and $1124{\pm}737$, $1185{\pm}755$ $ng{\cdot}h/mL$, respectively. The parametric 90% confidence intervals on the mean of the differences between the two formulations (test-reference) of the log transformed values of $AUC_t$, and $C_{max}$ were 0.9630 to 1.1383 and 0.8650 to 1.0446, respectively. The overall results indicate that the two formulations are bioequivalent and can be prescribe interchangeably.

• Journal of the Korean Society of Radiology
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• v.10 no.3
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• pp.215-222
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• 2016

X-ray mammography is the most effective method for the diagnosis of calcified lesions of various breast diseases. To reduce patient dose and to obtain optimal image required for diagnosis, the performance of the mammography system should be maintained continuously. Because the target (anode) angle of the X-ray tube is measured from the central X-ray, the effective angle can be slightly different in view of the position on the detector, which can result in degrading spatial resolution of the imaging within the field of view. In this study, we measured the MTF to examine spatial resolution for positions on the detector in the digital mammography system. For a tungsten wire of $50{\mu}m$ diameter, the highest spatial frequency was obtained. It meant that a wire diameter for measuring MTF through LSF should be small compared to the pixel size of the detector used in the mammography system. The spatial resolution showed slightly different performance according to positions on the detector. The center position gave the best spatial resolution and positions away from the center showed the degraded performance although the difference of the spatial resolution was small. The effective focal spot size of the full width at half maximum also showed similar result. It concluded that the slightly increase of the effective focal spot size gave the degradation of the spatial resolution for positions on the detector.

• Biomolecules & Therapeutics
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• v.25 no.3
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• pp.279-287
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• 2017

The chemical property of cinnamaldehyde is unstable in vivo, although early experiments have shown its obvious therapeutic effects on viral myocarditis (VMC). To overcome this problem, we used cinnamaldehyde as a leading compound to synthesize derivatives. Five derivatives of cinnamaldehyde were synthesized: 4-methylcinnamaldehyde (1), 4-chlorocinnamaldehyde (2), 4-methoxycinnamaldehyde (3), ${\alpha}$-bromo-4-methylcinnamaldehyde (4), and ${\alpha}$-bromo-4-chlorocinnamaldehyde (5). Neonatal rat cardiomyocytes and HeLa cells infected by coxsackievirus B3 (CVB3) were used to evaluate their antiviral and cytotoxic effects. In vivo BALB/c mice were infected with CVB3 for establishing VMC models. Among the derivatives, compound 4 and 5 inhibited the CVB3 in HeLa cells with the half-maximal inhibitory concentrations values of $11.38{\pm}2.22{\mu}M$ and $2.12{\pm}0.37{\mu}M$, respectively. The 50% toxic concentrations of compound 4 and 5-treated cells were 39-fold and 87-fold higher than in the cinnamaldehyde group. Compound 4 and 5 effectively reduced the viral titers and cardiac pathological changes in a dose-dependent manner. In addition, compound 4 and 5 significantly inhibited the secretion, mRNA and protein expressions of inflammatory cytokines TNF-${\alpha}$, IL-$1{\beta}$ and IL-6 in CVB3-infected cardiomyocytes, indicating that brominated cinnamaldehyde not only improved the anti-vital activities for VMC, but also had potent anti-inflammatory effects in cardiomyocytes induced by CVB3.

• The Korean Journal of Nuclear Medicine
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• v.24 no.1
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• pp.37-48
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• 1990

Detection of deep-seated abscesses is sometimes difficult with ultrasonogrpahy or computed tome graphy alone. Indium-111-labeled leukocyte has widely used in the localization of abscesses after introduction by Segal and Thakur in 1976. But there are some difficulties in using indium-111-oxine in our country because of hardness to get the radiopharmaceutical timely and long time for labeling leukocytes. So we peformed the indium-111-labeled leukocyte scan for establishment of the labeling procedure and clinical application. We labeled the mixed leukocytes from 36 ml of patient's blood using 4 ml of ACD solution, 7 ml of 6% hydroxyethyl starch solution $(HESPAN^{(R)})$, 1 mCi of indium-111 oxine, 5 ml of normal saline and centrifuge. It took about 2 hours for the preparation of radiolabeled leukocytes and attention for contamination was needed. The average injected dose of labeled mixed leukocytes was 465 uCi. The average number of injected leukocytes was $2.5\times10^8$ and the labeling ratio was $57{\pm}13%$ (Table 2, Fig. 5). These number and ratio were sufficient for the localization of abscess. About twenty per cent of indium was labeled to red blood cells and platelets (Fig. 6) and the half-life of injected radiolabeled leukocytes was 8.3 hours. Scan was performed in 9 patients who were suspected to have abscesses clinically or radiologically. Three patients were positive, in one patient who had abscess close to lower lumbar vertebrae was surgically drained and another 2 positive cases did not show abscess clearly on computed tomography, so only antibiotics were administrated and treated successfully. The negative 6 patients were improved without specific treatment. In conclusion, the use of indium-111 oxine labeled leukocytes for localization of abscesses were very specific and helpful in the decision of treatment considering its relatively simple labeling method, and could be easily performed providing timely supply of the radiopharmaceutical.

• Korean Journal of Food Science and Technology
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• v.4 no.2
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• pp.100-105
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• 1972

This experiment was conducted to investigate the combined effects of radiation and antiseptics on the keeping qualities of pork sausage, which was treated with potassium sorbate and AF-2(2-(-2-furyl)-3-(5-nitro-2-furyl)-acrylamide), and then followed by gamma radiation of 0.25, 0.5, and 0.75 Mrad. Amounts of treated antiseptics were a quarter, half, and full levels of their maximum permissible concentration. Irradiated and unirradiated sausages were stored for 50 days at $5^{\circ}C\;and\;25^{\circ}C$, and their changes in rancidity, volatile basic nitrogen, bacterial counts, pH, and sensory analysis were examined during the storage period. The results obtained are as follows: 1) Preservative effects of antiseptics were manifested at cold storage; antiseptics treatment of a quarter-level and unirradiation following low-temperature storage showed the same good keeping qualities as the combined treatment of full-level antiseptics and radiation of 0.25 Mrad following high-temperature storage. 2) There did not appear to recognize irradiation-odor, while color and odor were deteriorated intensively by storage temperature. Sausage irradiated with 0.75 Mrad has shown slightly noticeable off-odor at the end of storage at $25^{\circ}C$. 3) The most suitable radiation dose was considered to be 0.5 Mrad, which could extend the storage life about $2{\sim}3$ times longer than untreated.

• Journal of Ginseng Research
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• v.29 no.1
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• pp.37-43
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• 2005

We performed in vitro and in vivo studies to know whether the inhibitory effects of ginsenosides on $5-HT_{3A}$ receptor channel acctivity are coupled to anti-nausea and anti-vomiting action. In vitro study, we investigated the effect of compound K (CK) and M4, which are ginsenoside metabolites, on human $5-HT_{3A}$ receptor channel activity expressed in Xenopus oocytes using two-electrode voltage clamp technique. Treatment of CK or M4 themselves had no effect in both oocytes injected with $H_2O\;and\;5-HT_{3A}$ receptor cRNA. In oocytes injected with $5- HT_{3A}$ receptor cRNA, M4 treatment inhibited more potently 5-HT-induced inward peak current $(I_{5-HT})$ than CK with dose-dependent and reversible manner. The half-inhibitory concentrations $(IC_{50})$ of CK and M4 were $36.9\;\pm\;10.1\;and\;7.3\;\pm\;2.2\;{\mu}M$, respectively. The inhibition of $I_{5-HT}$ by M4 was non-competitive and voltage-independent. These results indicate that M4 might regulate $5-HT_{3A}$ receptors. In vivo experiments, injection of cisplatin (7.5 mg/kg, i.v.) induced both nausea and vomiting with 1 h latency. These episodes reached to peak after 2 h and persisted for 4 h. Pre-treatment of GTS (500 mg/kg, p.o.) significantly reduced cisplatin-induced nausea and vomiting by $51\;\pm\;8.4\;and\;48.8\;\pm\;6.4\%$ during 4 h compared to GIS­untreated group, respectively. These results show the possibility that in vitro inhibition of $5-HT_{3A}$ receptor channel activity by ginsenosides might be coupled to in vivo anti-emetic activity.