• Biomolecules & Therapeutics
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• v.24 no.2
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• pp.115-122
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• 2016

Sleep, which is an essential part of human life, is modulated by neurotransmitter systems, including gamma-aminobutyric acid (GABA) and dopamine signaling. However, the mechanisms that initiate and maintain sleep remain obscure. In this study, we investigated the relationship between melatonin (MT) and dopamine D2-like receptor signaling in pentobarbital-induced sleep and the intracellular mechanisms of sleep maintenance in the cerebral cortex. In mice, pentobarbital-induced sleep was augmented by intraperitoneal administration of 30 mg/kg MT. To investigate the relationship between MT and D2-like receptors, we administered quinpirole, a D2-like receptor agonist, to MT- and pentobarbital-treated mice. Quinpirole (1 mg/kg, i.p.) increased the duration of MT-augmented sleep in mice. In addition, locomotor activity analysis showed that neither MT nor quinpirole produced sedative effects when administered alone. In order to understand the mechanisms underlying quinpirole-augmented sleep, we measured protein levels of mitogen-activated protein kinases (MAPKs) and cortical protein kinases related to MT signaling. Treatment with quinpirole or MT activated extracellular-signal-regulated kinase 1 and 2 (ERK1/2), p38 MAPK, and protein kinase C (PKC) in the cerebral cortex, while protein kinase A (PKA) activation was not altered significantly. Taken together, our results show that quinpirole increases the duration of MT-augmented sleep through ERK1/2, p38 MAPK, and PKC signaling. These findings suggest that modulation of D2-like receptors might enhance the effect of MT on sleep.

• Journal of the Korean Magnetic Resonance Society
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• v.24 no.4
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• pp.104-116
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• 2020

Fipronil, the phenylpyrazole insecticide, is effective and used in various fields. Especially, fipronil was reliable because it was known to be specific on invertebrate animals than vertebrate animals including mammals. However, fipronil had potential risks that affect vertebrate animals as it blocks the gamma-aminobutyric acid (GABA) receptors that also exists in vertebrates as well as invertebrates. Therefore, it was necessary that harmful effects of fipronil on vertebrates are clarified. For this purpose, the zebrafish (Danio rerio) were used on behalf of vertebrate animals in present study. The zebrafish were exposed to 5 ㎍/L, 25 ㎍/L, and 50 ㎍/L of fipronil during 12, 24 and 72 hours. To closely observe toxic process, 12 hours and 24 hours of additional time point were set in the exposure test. Nuclear magnetic resonance (NMR)-based metabolomics is an approach to detect metabolic changes in organism resulted from external stimuli. In this study, NMR-based metabolomics showed the metabolic changes in zebrafish caused by fipronil exposure. Metabolic analysis revealed that fipronil interfered with energy metabolism and decreased the antioxidant ability in zebrafish. Antioxidant ability decline was remarkable at high exposure concentration. In addition, metabolic analysis results over time suggested that reactions for alleviating the excessive nerve excitation occurred in zebrafish after fipronil exposure. Through this study, it was elucidated that the adverse effects of fipronil on vertebrate animals are evident. The risk of fipronil on vertebrates can be no longer ignored. Moreover, this study has a meaning of practically necessary research for organism by examining the effects of fipronil at low concentrations existed in real environment.

• The Korean Journal of Pain
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• v.35 no.1
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• pp.43-58
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• 2022

Background: Current therapies are quite unsuccessful in the management of neuropathic pain. Therefore, considering the inhibitory characteristics of GABA mediators, the present systematic review and meta-analysis aimed to determine the efficacy of GABAergic neural precursor cells on neuropathic pain management. Methods: Search was conducted on Medline, Embase, Scopus, and Web of Science databases. A search strategy was designed based on the keywords related to GABAergic cells combined with neuropathic pain. The outcomes were allodynia and hyperalgesia. The results were reported as a pooled standardized mean difference (SMD) with a 95% confidence interval (95% CI). Results: Data of 13 studies were analyzed in the present meta-analysis. The results showed that administration of GABAergic cells improved allodynia (SMD = 1.79; 95% CI: 0.87, 271; P < 0.001) and hyperalgesia (SMD = 1.29; 95% CI: 0.26, 2.32; P = 0.019). Moreover, the analyses demonstrated that the efficacy of GABAergic cells in the management of allodynia and hyperalgesia is only observed in rats. Also, only genetically modified cells are effective in improving both of allodynia, and hyperalgesia. Conclusions: A moderate level of pre-clinical evidence showed that transplantation of genetically-modified GABAergic cells is effective in the management of neuropathic pain. However, it seems that the transplantation efficacy of these cells is only statistically significant in improving pain symptoms in rats. Hence, caution should be exercised regarding the generalizability and the translation of the findings from rats and mice studies to large animal studies and clinical trials.

• Journal of The Korean Society of Grassland and Forage Science
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• v.29 no.3
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• pp.263-268
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• 2009

This study was conducted to determine application possibility of mulberry (Morus alba) silage as a functional feed in feeding management of Korean native cattle for high quality beef production by analysing active components and antioxidative activity. The chemical analysis of mulberry silage indicates that the content of dry matter, crude protein, ether extract, crude fiber and crude ash was $28.41{\pm}3.12%,\;12.43{\pm}0.28%,\;2.47{\pm}0.18%,\;20.29{\pm}0.75%\;and\;6.98{\pm}0.12%$, respectively. The content of 1-deoxynojirimycin (1-DNJ), which is representative active ingredient of mulberry and blood sugar descending component, was 0.568 mg/g and the content of $\gamma$-Aminobutyric acid (GABA), which is blood pressure descending component, was 5,936.22 pmol. Mulberry silage used in this study did not contain flavonoids but did contain total phenols for 21.69 ${\mu}g/mg$. 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity was increased with increasing the concentration of mulberry silage extracts and there was above 50% of scavenging activity at the concentration of 0.25 mg/ml. Hydroxyl radical scavenging activity was also increased with increasing the concentration of silage extracts. Alkyl radical scavenging activity was high at the low concentration of silage extracts, which was above 50% of scavenging activity at the concentration of 0.125 mg/ml. The result of this study indicated that there was high possibility of mulberry silage as a functional feed for beef cattle.

• Progress in Medical Physics
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• v.28 no.4
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• pp.135-143
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• 2017

Chemical Exchange Saturation Transfer (CEST) imaging is a method to detect solutes based on the chemical exchange of mobile protons with water. The solute protons exchange with three different patterns, which are fast, slow, and intermediate rates. The CEST contrast can be obtained from the exchangeable protons, which are hydroxyl protons, amine protons, and amide protons. The CEST MR imaging is useful to evaluate tumors, strokes, and other diseases. The purpose of this study is to review the mathematical model for CEST imaging and for measurement of the chemical exchange rate, and to measure the chemical exchange rate using a 3T MRI system on several amino acids. We reviewed the mathematical models for the proton exchange. Several physical models are proposed to demonstrate a two-pool, three-pool, and four-pool models. The CEST signals are also evaluated by taking account of the exchange rate, pH and the saturation efficiency. Although researchers have used most commonly in the calculation of CEST asymmetry, a quantitative analysis is also developed by using Lorentzian fitting. The chemical exchange rate was measured in the phantoms made of asparagine (Asn), glutamate (Glu), ${\gamma}-aminobutyric$ acid (GABA), glycine (Gly), and myoinositol (MI). The experiment was performed at a 3T human MRI system with three different acidity conditions (pH 5.6, 6.2, and 7.4) at a concentration of 50 mM. To identify the chemical exchange rate, the "lsqcurvefit" built-in function in MATLAB was used to fit the pseudo-first exchange rate model. The pseudo-first exchange rate of Asn and Gly was increased with decreasing acidity. In the case of GABA, the largest result was observed at pH 6.2. For Glu, the results at pH 5.6 and 6.2 did not show a significant difference, and the results at pH 7.4 were almost zero. For MI, there was no significant difference at pH 5.6 or 7.4, however, the results at pH 6.2 were smaller than at the other pH values. For the experiment at 3T, we were only able to apply 1 s as the maximum saturation duration due to the limitations of the MRI system. The measurement of the chemical exchange rate was limited in a clinical 3T MRI system because of a hardware limitation.

• Journal of Pharmaceutical Investigation
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• v.35 no.3
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• pp.193-199
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• 2005

Gabapentin is an antiepileptic drug that is structurally similar to ${\gamma}-aminobutyric$ acid (GABA), but does not interact with the GABA receptor. It does not bind significantly to plasma proteins, and is excreted to unchanged form in the urine. The purpose of the present study was to evaluate the bioequivalence of two gabapentin capsules, $Neurontin^{TM}$ capsule 300 mg (Pfizer Pharm. Co., Ltd.) and Kuhnil $Gabapentin^{TM}$ capsule 300 mg (Kuhnil Pharm. Co., Ltd), according to the guidelines of the Korea Food and Drug Administration (KFDA). The release of gabapentin from the two gabapentin formulations in vitro was tested using KP VIII Apparatus II method with various dissolution media (pH 1.2, 4.0, 6.8 buffer solution and water). Twenty six healthy male subjects, $22.46{\pm}1.86$ years in age and $67.64{\pm}7.24$ kg in body weight, were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After a single capsule containing 300 mg as gabapentin was orally administered, blood samples were taken at predetermined time intervals and the concentrations of gabapentin in serum were determined using HPLC with fluorescence detector. The dissolution profiles of two formulations were similar at all dissolution media. In addition, the pharmacokinetic parameters such as $AUC_t$, $C_{max}$ and $T_{max}$ were calculated and ANOVA test was utilized for the statistical analysis of the parameters using logarithmically transformed $AUC_t$, $C_{max}$ and untransformed $T_{max}$. The results showed that the differences between two formulations based on the reference drug, $Neurontin^{TM}$ capsule 300 mg, were -2.03, -0.43 and 4.29% for $AUC_t$, $C_{max}$ and $T_{max}$, respectively. There were no sequence effects between two formulations in these parameters. The 90% confidence intervals using logarithmically transformed data were within the acceptance range of log 0.8 to log 1.25 $(e.g.,\;log\;0.89{\sim}log\;1.09\;and\;log\;0.91{\sim}log\;1.09$ for $AUC_t$ and $C_{max}$, respectively). Thus, the criteria of the KFDA bioequivalence guideline were satisfied, indicating Kuhnil $Gabapentin^{TM}$ capsule 300 mg was bioequivalent to $Neurontin^{TM}$ capsule 300 mg.

• Journal of Life Science
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• v.19 no.9
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• pp.1232-1238
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• 2009

Neurotransmitter release is regulated by various proteins of the active zone in the presynaptic nerve terminals. Dopamine (DA) is an essential neurotransmitter associated with the pathophysiology of diverse behavioral and mental illness such as schizophrenia and drug addiction. We measured synaptosomal DA release of knockout (KO) mice which lacked major genes related to neurotransmitter release. Synaptosomal DA uptake and release were performed and measured using [$^3H$]-DA and superfusion experiments. 3 of the 17 KO mice exhibited altered DA release compared to their littermate controls. In $Rim1{\alpha}$ KO, [$^3H$]-DA release evoked by membrane depolarization significantly decreased. Both basal (physiological buffer-evoked) and membrane depolarization-evoked DA release significantly decreased in dopaminergic conditional KO of $Rim1{\alpha}{\beta}$. Dopaminergic conditional KO of neurexin3 demonstrated a significant increase of membrane depolarization-evoked DA release. These data explain the similarities and distinctions between DA and other classical neurotransmitters such as glutamate and GABA ($\gamma$-aminobutyric acid) release. In conclusion, $Rim1{\alpha}$ and neurexin3 may be important regulators of presynaptic DA release and related to disorders of the nervous system.

• Journal of the Korean Society of Food Science and Nutrition
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• v.41 no.7
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• pp.963-969
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• 2012

This study evaluated the physicochemical properties of brown rice (BR) and germinated brown rice (GBR) in Korea. The protein content of BR was significantly higher than that of GBR. The amylose content of BR and GBR ranged from 17.42 to 18.48% and from 17.50 to 19.69%, respectively. The GBR contained higher ${\gamma}$-aminobutyric acid (GABA) content than that of BR. In an RVA examination, pasting temperatures of BR and GBR were $67.97{\sim}68.03^{\circ}C$. Texture analysis test showed that GBR Yeonghojinmi had the lowest hardness and highest stickiness. In conclusion, this study showed that compared to BR, GBR has a much softer texture, improved eating quality and increased GABA content.

• Journal of the Korean Society of Food Science and Nutrition
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• v.45 no.6
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• pp.828-834
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• 2016

The aim of this study was to evaluate the physicochemical properties and antioxidant and anti-proliferative activities of different plant parts of Elaeagnus umbellata Thunb. extracted with ethanol (EtOH). EtOH extract of stems presenting the highest content of polyphenols showed the strongest 1,1-diphenyl-2-picrylhydrazyl radical scavenging activity ($EC_{50}=54.04{\mu}g/mL$). The total content of free amino acids decreased in the order of leaves (6,179.12 mg/100 g)> stems (1,211.69 mg/100 g)> fruits EtOH extract (378.88 mg/100 g), and asparagine (1,907.57 mg/100 g), ${\gamma}-aminobutyric$ acid (300.17 mg/100 g), and proline (233.48 mg/100 g) were the major free amino acid in leaves, stems, and fruits, respectively. Five phenolic compounds in each extract were measured by using liquid chromatography- tandem mass spectrometry, and gallic acid (98.95 mg/100 g) and (+)-catechin (1,575.99 mg/100 g) were present as major components in leaves and stems, respectively. EtOH extract of leaves showed the highest anti-proliferative activity against HepG2 cells as measured by 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyltetrazoliumbromide and lactate dehydrogenase assay but had no effects on Chang liver cells.

• Journal of the Korean Society of Food Science and Nutrition
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• v.31 no.6
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• pp.1071-1077
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• 2002

The purpose of this study was investigated the effects of YK-209 mulberry leaves on disaccharidase activites of small intestine and blood glucose-lowering in diabetic rats induced with streptozotocin (STZ). Male Sprague-Dawley rats weighing 100$\pm$10 g were randomly assigned to one normal and four STZ-induced diabetic groups; YK-209 0% mulberry leaves diet (DM group),0.1% YK-209 mulberry loaves diet (DM-0.1Y group),0.2% YK-209mulberry leaves diet (DM -0.2Y group), and 0.4% YK-209 mulberry leaves diet (DM -0.4Y group). Diabetes was induced by intravenous injection of 55 mg/kg body weight of STZ in sodium citrate buffer (pH 4.3) via tail vein after 3 weeks feeding of experimental diets. Rats were sacrificed at the 9th day of diabetic states. The functional ingredients in the mulberry leaves, the 1-deoxynojirimycin (DNJ) contents of YK-209 mulberry leaves was higher than those of the Cheongil mulberry leaves. ${\gamma}$ -Aminobutyric acid (GABA) and rutin contents of YK-209 mulberry leaves were 1.3 and 1.4 times higher than those of the Cheongil mulberry leaves, respectively, and vitamin C contents of YK-209 mulberry leaves were also higher than those of the Cheongil mulberry leaves. Intestine index was increased in all diabetic groups, compared with normal group but not significantly different among all diadetic groups. Level of blood glucose was decreased in diadetic rats by supplementation YK-209 mulberry leaves. The disaccharidase activities in proximal part of intestine such as maltase, sucrase, and lactase in YK-209 mulberry leaves supplementation groups were significantly lower than those of DM group, In conclusion, this research indicated that the functional ingredients of YK 209 mulberry leaves were higher than those of the Cheongil leaveses, and YK-209 mulberry leaves has the hypoglycemic effect in STZ-induced diabetic rats.