• Toxicological Research
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• v.17
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• pp.71-77
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• 2001

The brain of the aged dog possesses senile plaques and amyloid angiopathy, which characterize Alzheimer's disease brains. We have defined the dementia condition of aged dogs and examined which mechanism(s) is responsible for the condition. A series of studies revealed that the dementia condition in aged dogs is significantly related to the number of apoptotic brain cells including both neurons and glial cells, but not to the number of senile plaques. On the other hand, 5-azacytidine (5AzC) is a cytidine analogue, and is thought to induce kinds of cell differentiation possibly through hypomethylation of genomic DNA. We have revealed neuronal apoptosis induced in 5AzC-treated fetal mice and PC12 cells. The ribosomal protein L4 (rpL4) gene is expressed prior to the apoptosis in the PC12 cell system. Therefore, the involvement of the rpL4 gene expression in age-related brain cell apoptosis in dogs may contribute to the investigation of Alzheimer's dementia.

• Toxicological Research
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• v.17
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• pp.41-45
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• 2001

The methods used for risk assessment from exposure to chemicals are well established. in most cases where toxicity other than carcinogenesis is being considered, the standard method relies on establishing the No Observed Adverse Effect Level (NOAEL) in the most sensitive animal toxicity study and using an appropriate safety factor (SF) to determine the exposure which would be associated with an acceptable risk. For carcinogens a different approach is used because it has been argued there is no threshold of effect. Thus mathematical equations are used to extrapolate from the high doses used in ani-mal experiments. These methods have been strongly criticised in recent years on several grounds. The most cogent criticisms are a) the equations are not based on a thorough understanding of the mechanisms of carcinogenesis and b) the outcome of a risk assessment based on such models varies more as a consequence of changes to the assumptions and equation used than it does from the data derived from carcinogenicity experiments. Other criticisms include the absence of any measure of the variance on the risk assessment and the selection of default values that are very conservative. Recent advances in the application of risk assessment emphasise that measures of both the exposure and the hazard should be considered as a distribution of values. The outcome of such a risk assessment provides an estimate of the distribution of the risks.

• Journal of Microbiology and Biotechnology
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• v.16 no.3
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• pp.349-354
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• 2006

Furaneol, a key aroma compound found in strawberry, pineapple, and processed foodstuffs, has been known to possess various biological activities on animal models. In this study, the antimicrobial effects of furaneol against human pathogenic microorganisms were investigated. The results indicated that furaneol displayed a broad spectrum of antimicrobial activities against Gram-positive and Gram-negative bacteria and fungi without hemolytic activity on human erythrocyte cells. To confirm the antifungal activity of furaneol, we examined the accumulation of intracellular trehalose as a stress response marker on toxic agents and its effect on dimorphic transition of Candida albicans. The results demonstrated that furaneol induced significant accumulation of intracellular trehalose and exerted its antifungal effect by disrupting serum-induced mycelial forms. These results suggest that furaneol could be a therapeutic agent having a broad spectrum of antimicrobial activity on human pathogenic microorganisms.

• The Korean Journal of Physiology and Pharmacology
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• v.13 no.3
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• pp.215-220
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• 2009

Chlorpheniramine is a potent first-generation histamine $H_1$ receptor antagonist that can increase action potential duration and induce QT prolongation in several animal models. Since block of cardiac human ether-a-go-go-related gene (hERG) channels is one of leading causes of acquired long QT syndrome, we investigated the acute effects of chlorpheniramine on hERG channels to determine the electrophysiological basis for its proarrhythmic potential. We examined the effects of chlorpheniramine on the hERG channels expressed in Xenopus oocytes using two-microelectrode voltage-clamp techniques. Chlorpheniramine induced a concentration-dependent decrease of the current amplitude at the end of the voltage steps and hERG tail currents. The $IC_{50}$ of chlorpheniramine-dependent hERG block in Xenopus oocytes decreased progressively relative to the degree of depolarization. Chlorpheniramine affected the channels in the activated and inactivated states but not in the closed states. The S6 domain mutations Y652A and F656A partially attenuated (Y652A) or abolished (F656A) the hERG current block. These results suggest that the $H_1$ antihistamine, chlorpheniramine is a blocker of the hERG channels, providing a molecular mechanism for the drug-induced arrhythmogenic side effects.

• Journal of Nutrition and Health
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• v.32 no.7
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• pp.767-774
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• 1999

This study was carrid out to examine a part of the mechanism for the etiology of diabetic complications. Thirty normal and forty streptozotocin(STZ)-induced diabetic rats were used as the animal models. Animals were sacrificed at the time points of 3 days, 1, 2, 4 and 6 weeks after STZ-injection and time course in body weight and organ weight, the levels of blood glucose, plasma lipid patterns, and atherogenic index were measured during 6 weeks. The STZ-diabetic animals showed 63% survival rate and fsting blood glucose levels of the diabetic animals measured in the range of 230-410mg/dL during the experimental period. The body weigh of diabetic animals decreased significantly throughout the experimental period and the relative weights of organs to body weight were significantly higher than the normal control ones. The enlargement of the kidney in the diabetic animals was especially remarkable. Plasma triglyceride concentration in diabetic rats substancially increased from the first week of onset of diabetes mellitus and maintained higher levels than the control ones throughout the whole experimental period. The plasma total cholesterol level and atherogenic index in the diabetic rats were significantly higher than the normal ones from the third day after STZ injection and showed a gradual increase with the duration of the disease. Throughout the experiment, the diabetic rats consistently showed a slightly lower HDL-cholesterol level compared to the normal animals. From the results of this study, it appears that the significant changes in blood lipid pattern in STZ-diabetic animals start from the first week after STZ injection.

• Journal of Yeungnam Medical Science
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• v.34 no.1
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• pp.19-28
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• 2017

The incidence of type 2 diabetes mellitus and insulin resistance is growing rapidly. Multiple organs including the liver, skeletal muscle and adipose tissue control insulin sensitivity coordinately, but the mechanism of skeletal muscle insulin resistance has not yet been fully elucidated. However, there is a growing body of evidence that lipotoxicity induced by mitochondrial dysfunction in skeletal muscle is an important mediator of insulin resistance. However, some recent findings suggest that skeletal mitochondrial dysfunction generated by genetic manipulation is not always correlated with insulin resistance in animal models. A high fat diet can provoke insulin resistance despite a coordinate increase in skeletal muscle mitochondria, which implies that mitochondrial dysfunction is not mandatory in insulin resistance. Furthermore, incomplete fatty acid oxidation by excessive nutrition supply compared to mitochondrial demand can induce insulin resistance without preceding impairment of mitochondrial function. Taken together we suggested that skeletal muscle mitochondrial overloading, not mitochondrial dysfunction, plays a pivotal role in insulin resistance.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.6
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• pp.2161-2166
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• 2015

Estrogen receptors (ERs) are steroid receptors located in the cytoplasm and on the nuclear membrane. The sequence similarities of human $ER{\alpha}$, mouse $ER{\alpha}$, rat $ER{\alpha}$, dog $ER{\alpha}$, and cat $ER{\alpha}$ are above 90%, but structures of $ER{\alpha}$ may different among species. Estrogen can be agonist and antagonist depending on its target organs. This hormone play roles in several diseases including breast cancer. There are variety of the relative binding affinity (RBA) of ER and estrogen species in comparison to $17{\beta}-estradiol$ (E2), which is a natural ligand of both $ER{\alpha}$ and $ER{\beta}$. The RBA of the estrogen species are as following: diethyl stilbestrol (DES) > hexestrol > dienestrol > $17{\beta}-estradiol$ (E2) > 17- estradiol > moxestrol > estriol (E3) >4-OH estradiol > estrone-3-sulfate. Estrogen mimetic drugs, selective estrogen receptor modulators (SERMs), have been used as hormonal therapy for ER positive breast cancer and postmenopausal osteoporosis. In the postgenomic era, in silico models have become effective tools for modern drug discovery. These provide three dimensional structures of many transmembrane receptors and enzymes, which are important targets of de novo drug development. The estimated inhibition constants (Ki) from computational model have been used as a screening procedure before in vitro and in vivo studies.

• Journal of The Korean Society of Agricultural Engineers
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• v.54 no.2
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• pp.55-65
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• 2012

In the winter season, when the ventilation system is operating, the fresh cold air from the slot-type openings of broiler house which directly reached the animal zone can cause various problems such as thermal stress, decreasing of feed and water consumption, occurrence of respiratory disease, and etc. Therefore it is very important to control the trajectory of aero-flow from the slot openings to induce an efficient thermal heat change. Jet-drop distance model was proposed to predict and control the jet-trajectory. However their study was restricted due to the small scaled model and difficulties of measuring the Jet-drop distance. In this study, CFD was applied to analyze qualitatively and quantitatively the jet-drop distance in a real broiler house. The various variables were considered such as installed slot-angle, designed ventilation rate, and the outdoor ambient temperature. From the present study, two linear-regression models using the Jet-drop factor and corrected Archimedes number, and their R-squared values 0.744 and 0.736, respectively, were used. From this study, the applicability of CFD on the analysis of Jet-drop distance model was confirmed.

• The Korean Journal of Physiology and Pharmacology
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• v.22 no.2
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• pp.155-162
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• 2018

3-(2-Carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP), a competitive N-methyl-D-aspartate (NMDA) receptor antagonist, produces rapid antidepressant-like effects in animal models of depression. However, the molecular mechanisms underlying these behavioral actions remain unknown. Here, we demonstrate that CPP rapidly stimulates histone deacetylase (HDAC) 5 phosphorylation and nuclear export in rat hippocampal neurons. These effects are accompanied by calcium/calmodulin kinase II (CaMKII) and protein kinase D (PKD) phosphorylation. Behavioral experiments revealed that viral-mediated hippocampal knockdown of HDAC5 blocked the antidepressant effects of CPP in stressed animals. Taken together, our results imply that CPP acts via HDAC5 and suggest that HDAC5 is a common regulator contributing to the antidepressant actions of NMDA receptor antagonists such as CPP.

• Journal of Microbiology and Biotechnology
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• v.22 no.9
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• pp.1307-1309
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• 2012

Haemophilus parasuis causes contagious porcine Gl$\ddot{a}$sser's disease leading to severe losses in the swine industry. In this study, we established an efficient Escherichia coli-based system for the expression of H. parasuis major outer-membrane protein (MOMP) that has been known as a good vaccine candidate against Gl$\ddot{a}$sser's disease. Use of an E. coli-derived pelB leader sequence made it possible to produce recombinant MOMP (rMOMP) as the soluble forms without an additional refolding process. Using two different animal models, it was evaluated that the rMOMP was capable of inducing a significant immune response and providing protection against H. parasuis infection.