• Biomolecules & Therapeutics
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• v.18 no.4
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• pp.448-453
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• 2010

Drug-induced long QT syndrome is known to be associated with the onset of torsades de pointes (TdP), resulting in a fatal ventricular arrhythmia. QT interval prolongation can result from blocking the human ether-a-go-go-related gene (hERG) channel, which is important for the repolarization of cardiac action potential. Nicardipine, a Ca-channel blocker and antihypertensive agent, has been reported to increase the risk of occasional serious ventricular arrhythmias. We studied the effects of nicardipine on hERG $K^+$ channels expressed in HEK293 cells and Xenopus oocytes. The cardiac electrophysiological effect of nicardipine was also investigated in this study. Our results revealed that nicardipine dose-dependently decreased the tail current of the hERG channel expressed in HEK293 cells with an $IC_{50}$ of 0.43 ${\mu}M$. On the other hand, nicardipine did not affect hERG channel trafficking. Taken together, nicardipine inhibits the hERG channel by the mechanism of short-term channel blocking. Two S6 domain mutations, Y652A and F656A, partially attenuated (Y652A) or abolished (F656A) the hERG current blockade, suggesting that nicardipine blocks the hERG channel at the pore of the channel.

• Journal of Physiology & Pathology in Korean Medicine
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• v.25 no.2
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• pp.242-245
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• 2011

Socheongryong-tang has been used for the treatment of inflammatory allergic diseases such as allergic rhinitis and bronchial asthma in Asian countries. This study was conducted to investigate the safety of Socheongryong-tang in rats. The safety of this tang on acute toxicity was evaluated by single dose toxicity study. Rats were orally administrated in a single dose of 0 and 2000 mg/kg (limited dose) Socheongryong-tang. There were 7 rats in each groups. All animals were sacrificed after 14 days of treatment. After single administration, mortality, clinlcal signs, body weight changes and gross pathological findings were observed for 14 days. Three parameters were tested: organ weight measurement, clinical chemistry, and hematology. In this study with rats, Socheongryong-tang treatment did not show any acute toxicity. No mortality was noted for 14 days of treatment. There were no adverse effects on clinical signs, body weight, organ eight and gross pathological findings at all treatment groups. The clinical chemistry parameters attesting to liver and kidney functions as well as the hematological parameters were within the normal ranges. From single dose toxicity study with rats, it is considered that $LD_{50}$ of Socheongryong-tang is over 2000 mg/kg in oral administration. This finding of the safety on single dose toxicity study of Socheongryong-tang are expected to strengthen the position of Socheongryong-tang as nontoxic medicine.

• Korean Journal of Pharmacognosy
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• v.34 no.1 s.132
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• pp.80-85
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• 2003

Water extract from Astragali Radix (AR) was tested for the safety using Ames, Bacillus subtilis Rec, and umu gene expression mutagenicity tests. Mutagenic activity in any assays we tested was not found. In Ames test, Salmonella typhimurium TA98 and TA 100 were used to identify mutagenic property, and the number of histidine revertants was measured. In the Recassay, Bacillus subtilis ${H-17(Rec^+)\;and\;M-45(Rec^-)}$ strains were used to test DNA damage activity. In the SOS umu test, Salmonella typhimurium TA1535 containing plasmid pSK1002 was used as a test strain, and we monitored the levels of umu operon expression by measuring the ${\beta}-galactosidase$ activity. From the results, there was no DNA damage and mutagenicity of AR. Hepatotoxicity of AR to female ICR mice was also monitored by the measurements of s-GOT, s-GPT, LDH activities after oral feeding for 15 days. AR was not shown any significant changes of s-GOT, s-GPT and LDH activities in mice sera.

• Journal of Food Hygiene and Safety
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• v.7 no.2
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• pp.77-82
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• 1992

In order to investigate the protein binding characteristics of braD6n and hematoxy6n to bovine semm albumin (BSA), the fluorescence probe method was adopted. Brazilin and hematoxy6n showed strong binding affinity for BSA. It was also confirmed that hematoxy6n was bound to BSA stronger than braDlin. The association constants were decreased by the elevation of concentrations of brazilin and hematoxylin. It might be due to the complex formation of the probe and both compounds or the interaction between the probe-protein complex and both compounds. The bindings between both compounds and BSA were dependent on pH and ionic strength. It seems that electrostatic force as weD as hydrophobic force is involved in the binding of braD6n and bematoxylin to BSA.

• Neonatal Medicine
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• v.15 no.2
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• pp.119-122
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• 2008

Clinical research is a necessity, not an option, for developing better and new medicines and therapeutic modalities. But in the course of clinical research, there are rules and guidelines that should be followed to ensure the due respect for persons, beneficence, and justice for persons who voluntarily participate in the research as described in the Belmont Report. Good Clinical Practice (GCP) is an "international scientific and ethical quality standard for designing, conducting, recording, and reporting" clinical trials. The main purposes of GCP would be to protect rights, safety, and well-being of trial subjects, in compliance with the principles of Declaration of Helsinki, and to assure that the data obtained from clinical trials are credible. In order to achieve these, investigators must be fully aware of the meanings as well as actual procedures involved in the research and should make the best effort to comply with GCP. For those individuals who belong to vulnerable populations, such as neonates, in addition to the general principles of GCP, further measures to ensure added protection should be implemented. It is our duty to develop and provide better care through clinical research even for neonates. But in doing so, we have to make sure that the importance of protecting the rights, safety, and well-being of the subjects supersede the interests of science and society.

• Journal of Ginseng Research
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• v.36 no.3
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• pp.242-247
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• 2012

Chondrocyte apoptosis has been recognized as an important factor in the pathogenesis of osteoarthritis (OA). Hydrogen peroxide ($H_2O_2$), which produces reactive oxygen species, reportedly induces apoptosis in chondrocytes. The ginsenoside $Rb_1$ (G-$Rb_1$) is the principal component in ginseng and has been shown to have a variety of biological activities, such as anti-arthritis, anti-inflammation, and anti-tumor activities. In this study, we evaluated the effects of G-$Rb_1$ on the mitochondrial permeability transition (MPT) and caspase-3 activity of chondrocyte apoptosis induced by $H_2O_2$. Cultured rat articular chondrocytes were exposed to $H_2O_2$ with or without G-$Rb_1$ and assessed for viability, MPT, Bcl-xL/Bax expression, caspase-3 activity, and apoptosis. The co-treatment with G-$Rb_1$ showed an inhibition of MPT, caspase-3 activity, and cell death. Additionally, the levels of the apoptotic protein Bax were significantly lower and the levels of the anti-apoptotic protein Bcl-xL were higher compared with $H_2O_2$ treatment alone. The results of this study demonstrate that G-$Rb_1$ protects chondrocytes against $H_2O_2$-induced apoptosis, at least in part via the inhibition of MPT and caspase-3 activity. These results demonstrate that G-$Rb_1$ is a potentially useful drug for the treatment of OA patients.

• CELLMED
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• v.8 no.2
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• pp.8.1-8.5
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• 2018

Nitric oxide (NO) is a small diffusible molecule which plays an important role in various physiological activities. NO is a notable molecule, functioning as a cytotoxic agent and cellular messenger. There has been considerable interest in NO production by activated macrophages because this gaseous metabolite plays a fundamental role in the cytotoxic and cytostatic effects of macrophages towards invasive micro-organisms and tumour cells. No is a bioactive free radical that has been implicated in many physiological functions, plays a critical role during inflammation and therefore constitutes a potential target for developing therapeutics for inflammatory diseases. The use of medicinal plants by the population has been an important alternative the resource in the treatment of various diseases. Its growing acceptance in the medical community has been due to the fact that several plants with biological activities have been scientifically investigated and their efficacy and safety have been proven. In this review, discussed suppressive effects of No production by traditional medicines in RAW 264.7 and THP-1 macrophages.

• Toxicological Research
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• v.29 no.3
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• pp.217-219
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• 2013

Hypertension is a serious health problem due to high frequency and concomitant other diseases including cardiovascular and renal dysfunction. Olmesartan cilexetil is a new antihypertensive drug associated with angiotensin II receptor antagonist. This study was conducted to evaluate the mutagenicity of olmesartan cilexetil by bacterial reverse mutation test using Salmonella typhimurium (TA100, TA1535, TA98, and TA1537) and Escherichia coli (WP2 uvrA). At the concentrations of 0, 62, 185, 556, 1667, and 5000 ${\mu}g$/plate, olmesartan cilexetil was negative in both Salmonella typhimurium and Escherichia coli regardless of presence or absence of metabolic activation system (S9 mix). These results demonstrate that olmesartan cilexetil does not induce bacterial reverse mutation.

• Toxicological Research
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• v.17
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• pp.205-210
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• 2001

One of the major focuses and perhaps the greatest challenges during the past decade in the discipline of immunotoxicology has been the elucidation of the molecular mechanisms responsible for immunotoxicity by specific agents. Much is currently understood about the basic underlying intracellular processes that control leukocyte effector function. This fundamental information in cell biology can now be applied toward developing systematic approaches, through the application of cell and molecular biology techniques, to identify the intracellular targets and processes disrupted by immunotoxicants. The objective of this paper is two fold. First to discuss fundamental principles of experimental design aimed at elucidation of cellular mechanisms in immunotoxicology; and second to discuss the application of molecular biology techniques in characterizing the mechanism of TCDD-induced B cell dysfunction as a working example.

• 대한임상약리학회:학술대회논문집
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• 1998.12a
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• pp.68-68
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• 1998