• 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.

• The Korean Journal of Physiology and Pharmacology
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• v.17 no.2
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• pp.127-132
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• 2013

Ginsenosides, one of the active ingredients of Panax ginseng, show various pharmacological and physiological effects, and they are converted into compound K (CK) or protopanaxatriol (M4) by intestinal microorganisms. CK is a metabolite derived from protopanaxadiol (PD) ginsenosides, whereas M4 is a metabolite derived from protopanaxatriol (PT) ginsenosides. The ${\gamma}$-aminobutyric acid $receptor_C$ ($GABA_C$) is primarily expressed in retinal bipolar cells and several regions of the brain. However, little is known of the effects of ginsenoside metabolites on $GABA_C$ receptor channel activity. In the present study, we examined the effects of CK and M4 on the activity of human recombinant $GABA_C$ receptor (${\rho}$ 1) channels expressed in Xenopus oocytes by using a 2-electrode voltage clamp technique. In oocytes expressing $GABA_C$ receptor cRNA, we found that CK or M4 alone had no effect in oocytes. However, co-application of either CK or M4 with GABA inhibited the GABA-induced inward peak current ($I_{GABA}$). Interestingly, pre-application of M4 inhibited $I_{GABA}$ more potently than CK in a dose- dependent and reversible manner. The half-inhibitory concentration ($IC_{50}$) values of CK and M4 were $52.1{\pm}2.3$ and $45.7{\pm}3.9{\mu}M$, respectively. Inhibition of $I_{GABA}$ by CK and M4 was voltage-independent and non-competitive. This study implies that ginsenoside metabolites may regulate $GABA_C$ receptor channel activity in the brain, including in the eyes.

• The Korean Journal of Physiology and Pharmacology
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• v.17 no.2
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• pp.175-180
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• 2013

Resveratrol is a phytoalexin found in grapes, red wine, and berries. Resveratrol has been known to have many beneficial health effects, such as anti-cancer, neuroprotective, anti-inflammatory, and life-prolonging effects. However, relatively little is known about the effects of resveratrol on the regulation of ligand-gated ion channels. We have previously reported that resveratrol regulates subsets of homomeric ligand-gated ion channels such as those of 5-$HT_{3A}$ receptors. The ${\gamma}$-aminobutyric $acid_C$($GABA_C$) receptor is mainly expressed in retinal bipolar cells and plays an important role in visual processing. In the present study, we examined the effects of resveratrol on the channel activity of homomeric $GABA_C$ receptor expressed in Xenopus oocytes injected with cRNA encoding human $GABA_C$ ${\rho}$ subunits. Our data show that the application of GABA elicits an inward peak current ($I_{GABA}$) in oocytes that express the $GABA_C$ receptor. Resveratrol treatment had no effect on oocytes injected with $H_2O$ or with $GABA_C$ receptor cRNA. Co-treatment with resveratrol and GABA inhibited $I_{GABA}$ in oocytes with $GABA_C$ receptors. The inhibition of $I_{GABA}$ by resveratrol was in a reversible and concentration-dependent manner. The $IC_{50}$ of resveratrol was $28.9{\pm}2.8{\mu}M$ in oocytes expressing $GABA_C$ receptor. The inhibition of $I_{GABA}$ by resveratrol was in voltage-independent and non-competitive manner. These results indicate that resveratrol might regulate $GABA_C$ receptor expression and that this regulation might be one of the pharmacological actions of resveratrol on the nervous system.

• 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.

• The Korean Journal of Food And Nutrition
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• v.27 no.4
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• pp.692-698
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• 2014

In this study, we investigated cancer cell growth inhibitory effects of kimchi extracts obtained from cabbage kimchi. Kimchi extracts (S46h, S47h, S48h) were obtained from the samples fermented at $15^{\circ}C$ for 46 h, 47 h, and 48 h during the first 10 days, which were subsequently stored at $-1.4^{\circ}C$ in kimchi refrigerator (hereinafter DV kimchi extracts). The samples showed a higher anti-proliferative effect against AGS (human, gastric adenocarcinoma) cell lines compared to control kimchi extract (S0h) obtained from sample stored at $-1.4^{\circ}C$ without fermentation. The DV kimchi contained higher levels of ${\gamma}$-aminobutyric acid (GABA) and ornithine compared to the control kimchi extract. Among the DV kimchi extracts, the S46h sample showed a higher anti-proliferative effect against the cancer cell growth and contained higher amount of GABA than the other kimchi samples. These results suggest that the consumption of DV kimchi can be more beneficial, as it is rich in GABA and ornithine. Therefore, it could be helpful in retarding the proliferation of cancer cells compared to the control kimchi.

• Journal of Dairy Science and Biotechnology
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• v.31 no.2
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• pp.143-152
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• 2013

Aminobutyric acid (GABA), a major inhibitory neurotransmitter in the central nervous system of animals, has several physiological effects including anti-hypertensive, diuretic, tranquilizing, and anti-stress properties, in humans. The purpose of this study was to investigate Lactobacillus plantarum K74, which was isolated from kimchi and selected as a strain with a high ability to produce GABA, to develop a new starter culture for fermented milk production. L. plantarum K74 produced $134.52{\mu}g/mL$ GABA in MRS broth containing 1% MSG, $212.27{\mu}g/mL$ GABA in MRS broth containing 2% MSG, and $234.63{\mu}g/mL$ GABA in MRS broth containing 3% MSG. The optimum growth temperature of L. plantarum K74 was $34^{\circ}C$, reaching a pH of 4.4 after 18 hours of growth. L. plantarum K74 was most sensitive to novobiocin out of 16 different antibiotics tested, and was most resistant to kanamycin and polymyxin B. L. plantarum K74 did not produce ${\beta}$-glucuronidase, a carcinogenic enzyme, and was comparatively tolerant to bile juice and low pH. Furthermore, it displayed resistance to Escherichia coli, Salmonella typhimurium, and Staphylococcus aureus at rates of 54.9%, 46.3%, and 0.7%, respectively.

• Applied Microscopy
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• v.34 no.4
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• pp.285-294
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• 2004

We investigated the morphology, distribution and synaptic connectivity of cholinergic neurons in the mouse retina by immunocytochemistry, using antisera against choline acetyltransferase (ChAT). ChAT-immunoreactive amacrine cells fall into two groups according to the localization of their somas in the retina: one is situated in the inner nuclear layer (INL), near the border of the inner plexiform layer (IPL), and the other is displaced in the ganglion cell layer (GCL). The dendrites of amacrine cells from the INL ramify in sublamina a and that of the displaced amacrine cells ramify in sublamina b of the IPL. Double labeling with an antisera against ChAT and r-aminobutyric acid (GABA) demonstrated that these labeled cells formed a subpopulation of GABAergic amacrine cells. The synaptic connectivity of ChAT-immunoreactive amacrine cells was identified in the IPL by electron microscopy. The most frequent synaptic input of ChAT-labeled amacrine cells was from bipolar cells in both sublaminae a and b of the IPL, followed by labeled amacrine cells and unlabeled amacrine cells. Their primary output targets were onto ganglion cells in both sublaminae a and b and output onto ganglion cells was more frequently observed in sublamina b of the IPL. Our results suggest that cholinergic amacrine cells in the mouse retina are very similar to their counter parts in other mammals, and they can attribute a major role in the pathway feeding into directionally selective ganglion cells.

• Journal of the Korean Society of Food Science and Nutrition
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• v.39 no.8
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• pp.1201-1206
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• 2010

As a means to increase the production and consumption of the brown colored rice with high content of GABA ($\gamma$-aminobutyric acid), this study was conducted to develop brown colored rice tea. After roasting at various temperatures and times, color values and GABA content of the brown colored rice were analyzed. Physicochemical properties such as browning, turbidity, reducing sugar, soluble solid, total polyphenol and pH of brown colored rice tea were determined after the rice powder was put into tea bags and leached in hot water. Sensory characteristics were investigated for three kinds of tea roasted at $170^{\circ}C$ for 10, 20 and 30 min. As the roasting temperature and time increased, L, a and b values decreased as well as GABA content. The brown colored rice roasted at $170^{\circ}C$ for 10 min contained the highest content of GABA. Browning, turbidity, reducing sugar, soluble solid and total polyphenol of the brown colored rice tea increased as the roasting temperature and time increased, on the contrary, pH decreased. The brown colored rice tea roasted for 30 min was preferred the most in color, flavor, taste and overall acceptance. From this result, the brown colored rice tea needs to be manufactured by a combination of the brown colored rice roasted at $170^{\circ}C$ for 10 min and 30 min to satisfy the consumer's preference and high content of GABA.

• 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.