• Progress in Medical Physics
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• v.29 no.1
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• pp.29-41
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• 2018

The objective of this study was to evaluate the chemical exchange saturation transfer (CEST) effect of amino acids and neurotransmitters, which exist in the human brain, depending on the concentration, pH, and amplitude of the saturation radiofrequency field. Phantoms were developed with asparagine (Asn), ${\gamma}-aminobutyric$ acid (GABA), glutamate (Glu), glycine (Gly), and myoinositol (MI). Each chemical had three different concentrations of 10, 30, and 50 mM and three different pH values of 5.6, 6.2, and 7.4. Full Z-spectrum CEST images for each phantom were acquired with a continuous-wave radiofrequency (RF) saturation pulse with two different $B_1$ amplitudes of $2{\mu}T$ and $4{\mu}T$ using an animal 9.4T MRI system. A voxel-based CEST asymmetry was mapped to evaluate exchangeable protons based on amide (-NH), amine ($-NH_2$), and hydroxyl (-OH) groups for the five target molecules. For all target molecules, the CEST effect was increased with increasing concentration and B1 amplitude; however, the CEST effect with varying pH displayed a different trend depending on the characteristics of the molecule. On CEST asymmetric maps, Glu and MI were well visualized around 3.0 and 0.9 ppm, respectively, and were well separated macroscopically at a pH of 7.4. The exchange rates of Asn, Glu, BABA, and Gly usually decreased with increasing pH. The CEST effect was dependent on the concentration, acidity of the target molecules, and B1 amplitude of the saturation RF pulse. The CEST effect for Asn can be observed in a 9.4T MRI system. The results of this study are based on applying the CEST technique in patients with neurodegenerative diseases when proteins in the brain are increased with disease progression.

• The Korean Journal of Pharmacology
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• v.28 no.1
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• pp.27-40
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• 1992

The purpose of the present study is an attempt to investigate the effect of intraventricular taurine, which is a naturally occuring amino acid containing sulfur and has inhibitory action in brain, on heart rate and blood pressure in the urethane anesthetized rabbits and also to elucidate the mechanism of its cardiovascular actions. Taurine $(0.15{\sim}1.5\;mg)$ injected into the lateral ventricle of anesthetized normontensive rabbits produced a dose-related fall in arterial blood pressure and heart rate, which were marked and long-lasting along with considerable respiratory depression. However, the intravenous administration of taurine at the same dose with intraventricular injection did not induce any changes in blood pressure as well as heart rate. Depressor responses induced by taurine were inhibited significantly by pretreatment with chlorisondamine, clonidine, strychnine and bicuculline but not by atropine, vagotomy, propranolol and metoclopramide. Moreover, taurine did not affect the pressor responses of norepinephrine. Taurine-induced bradycardic effects were blocked clearly by pretreatment with chlorisondamine, propranolol, clonidine, strychnine and bicuculline, while they were not influenced by atropine, vagotomy and metoclopramide. These experimental results suggest that intraventricular taurine causes long-lasting hypotensive and bradycardic actions, and that these cardiovascular effects may be exerted through taurinergic (glycinergic) and GABAergic receptors which are associated with catecholaminergic neurons in brain.

• Asian-Australasian Journal of Animal Sciences
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• v.26 no.6
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• pp.804-811
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• 2013

The effects and significance of ${\gamma}$-amino butyric acid (GABA) producing bacteria (GPB) on in vitro rumen fermentation and reduction of biogenic amines (histamine, methylamine, ethylamine, and tyramine) using corn meal as a substrate were determined. Ruminal samples collected from ruminally fistulated Holstein cows served as inoculum and corn was used as substrate at 2% dry matter (DM). Different inclusion rates of GPB and GABA were evaluated. After incubation, addition of GPB had no significant effect on in vitro fermentation pH and total gas production, but significantly increased the ammonia nitrogen ($NH_3$-N) concentration and reduced the total biogenic amines production (p<0.05). Furthermore, antioxidation activity was improved as indicated by the significantly higher concentration of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) among treated samples when compared to the control (p<0.05). Additionally, 0.2% GPB was established as the optimum inclusion level. Taken together, these results suggest the potential of utilizing GPB as feed additives to improve growth performance in ruminants by reducing biogenic amines and increasing anti-oxidation.

• The Korean Journal of Physiology and Pharmacology
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• v.21 no.6
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• pp.695-702
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• 2017

The sustained tonic currents ($I_{tonic}$) generated by ${\gamma}$-aminobutyric acid A receptors ($GABA_{A}Rs$) are implicated in diverse age-dependent brain functions. While various mechanisms regulating $I_{tonic}$ in the hippocampus are known, their combined role in $I_{tonic}$ regulation is not well understood in different age groups. In this study, we demonstrated that a developmental increase in GABA transporter (GAT) expression, combined with gradual decrease in $GABA_AR{\alpha}_5$ subunit, resulted in various $I_{tonic}$ in the dentate gyrus granule cells (DGGCs) of preadolescent rats. Both GAT-1 and GAT-3 expression gradually increased at infantile ($P_{6-8}$ and $P_{13-15}$) and juvenile ($P_{20-22}$ and $P_{27-29}$) stages, with stabilization observed thereafter in adolescents ($P_{34-36}$) and young adults ($P_{41-43}$). $I_{tonic}$ facilitation of a selective GAT-1 blocker (NO-711) was significantly less at $P_{6-8}$ than after $P_{13-15}$. The facilitation of $I_{tonic}$ by SNAP-5114, a GAT-3 inhibitor, was negligible in the absence of exogenous GABA at all tested ages. In contrast, $I_{tonic}$ in the presence of a nonselective GAT blocker (nipecotic acid, NPA) gradually decreased with age during the preadolescent period, which was mimicked by $I_{tonic}$ changes in the presence of exogenous GABA. $I_{tonic}$ sensitivity to L-655,708, a $GABA_AR{\alpha}_5$ subunit inverse agonist, gradually decreased during the preadolescent period in the presence of NPA or exogenous GABA. Finally, Western blot analysis showed that the expression of the $GABA_AR{\alpha}_5$ subunit in the dentate gyrus gradually decreased with age. Collectively, our results suggested that the $I_{tonic}$ regulation of altered GATs is under the final tune of $GABA_AR{\alpha}_5$ subunit activation in DGGCs at different ages.

• YAKHAK HOEJI
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• v.52 no.3
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• pp.195-200
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• 2008

Gabapentin, [1-(aminomethyl) cyclohexaneacetic acid], a structural analog of $\gamma$-aminobutyric acid (GABA), is being developed for the treatment of epilepsy. Unlike GABA, gabapentin crosses the blood-brain barrier after systemic administration. Gabapentin is an effective antiepileptic drug in patients with partial and secondarily generalized seizures who are uncontrolled with use of existing anticonvulsant drug therapy. The purpose of the present study was to evaluate the bioequivalence of two gabapentin 400 mg capsules, $Neurontin^{(R)}$ capsule 400 mg (Pfizer Inc.) and Gabatin capsule 400 mg (Korean Drug 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, 23.58$\pm$1.50 years in age and 66.74$\pm$8.31 kg in body weight, were divided into two groups and a randomized 2$\times$2 cross-over study was employed. After one capsule containing 400 mg as gabapentin were orally administered, blood was 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, $Neurontin^{(R)}$ capsule 400 mg, were 2.04, -3.68 and 16.79% 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 0.91$\sim$log 1.16 and log 0.87$\sim$log 1.11 for $AUC_t$ and $C_{max}$, respectively). Thus, the criteria of the KFDA bioequivalence guideline were satisfied, indicating Gabatin capsule 400 mg was bioequivalent to $Neurontin^{(R)}$ capsule 400 mg.

• Journal of Life Science
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• v.29 no.5
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• pp.564-569
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• 2019

Heavy drinking disrupts the nervous system by activation of GABA receptors and inhibition of glutamate receptors, thereby preventing short-term memory formation. Degradation of cognition by alcohol induces blackouts, and it can lead to alcoholic dementia if repeated. Therefore, drugs need to be developed to prevent alcohol-induced blackout. In this study, we confirmed the effect of an ethanol extract of Cassia obtusifolia seeds (COE) on alcohol-induced memory impairment. The effects of COE and ethanol on cognitive functions mice were examined using the passive avoidance and Y-maze tests. The manner in which alcohol affects long-term potentiation (LTP) in relation to the learning and memory was confirmed by electrophysiology performed on mouse hippocampal slices. We also measured N-methyl-D-aspartate (NMDA) receptor-mediated field excitatory synapses (fEPSPs), which have a known association with cognitive impairment caused by ethanol. Ethanol caused memory impairments in passive avoidance and Y-maze tests. COE prevented these ethanol-induced memory impairments in these tests. Ethanol also blocked LTP induction in the mouse hippocampus, and COE prevented this ethanol-induced LTP deficit. Ethanol decreased NMDA receptor-mediated fEPSPs in the mouse hippocampus, and this decrease was prevented by COE. These results suggest that COE might be useful in preventing alcohol-induced neurological dysfunctions, including blackouts.

• Food Science and Preservation
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• v.20 no.4
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• pp.564-572
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• 2013

We investigated the quality characteristics of brewing brown rice vinegar through a traditional static fermentation process. Accordingly, we decided to compare the physicochemical characteristics of brewing vinegar at different temperatures and filtration methods. In four to five weeks' time, the acetic acid fermentation exhibited the highest titratable acidity and then it eventually decreased. The titratable acidity was affected by the filtration method. It was revealed that the titratable acidity was higher in the forced filtration than the traditional filtration method. Various organic acids were detected in order to initialize the fermentation stage and as the fermentation progressed, only the acetic acid could be detected. The total free amino acid content was higher at a temperature of $30^{\circ}C$ than at $20^{\circ}C$. Moreover, the free amino acid content was dependent on the acetate content during the acetic fermentation process. The main bioactive substance of the ${\gamma}$-aminobutyric acid content was more than twice at a fermentation temperature of $30^{\circ}C$ compared to the fermentation temperature of $20^{\circ}C$. Furthermore, the total amino acid and essential amino acid content at a temperature of $30^{\circ}C$ was excellent. The quality of the brown rice vinegar via forced filtration method at a temperature of $30^{\circ}C$ was the most excellent. Based on these results, the fermentation temperature and the use of nuruks (fermenting agent) affected the quality of the brown rice vinegar, and an appropriate method to consider its purpose is required.

• Food Science and Preservation
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• v.15 no.1
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• pp.118-124
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• 2008

The chemical compositions and antioxidant activities of four different colored rice cultivars (white-colored rice: WCR, brown-colored rice: BCR, brown-colored waxy rice: BCWR, black-colored rice: BKCR) were investigated to evaluate the quality characteristics of the new brown rice cultivars. There was no significant differences in chemical compositions amongst the four rice cultivars, although WCR had higher amount of carbohydrate than did the other rice cultivars. 'The major fatty acids in the four rice cultivars were linoleic, oleic and palmitic acids, which accounted for about 96% of total fatty acids. Of note, higher amounts of saturated fatty acids (24.8%) and lower amount of unsaturated fatty acids (75.2%) were observed in BKCR than in the other rice cultivars. Two brown-colored rice cultivars, BCR and BCWR, possessed higher amounts of linoleic acid (40.8% and 42.1%, respectively) than did the other cultivars. The highest level of ${\alpha}$-tocopherol was found in WCR (51.3mg%), followed by BKCR (38.6mg%), BCWR (37.2 mg%), and BCR (34.5mg%). Free amino acid analysis showed that aspartic and glutamic acids were major amino acids of all cultivars, whereas phenylalanine, lysine, and histidine were minor. Particularly, relatively higher contents of aspartic and glutamic acids were found in BKCR, while relatively higher levels of alanine and ${\gamma}$-aminobutyric acid (GABA) were observed in BCR and BCWR. Also, BKCR had the highest phenolic content and antioxidant activity of any cultivar, followed by the two brown-colored rice cultivars and WCR. These results suggested that the new brown rice cultivars may possess quality characteristics intermediate between those of WCR and BCR.

• Microbiology and Biotechnology Letters
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• v.41 no.2
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• pp.168-175
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• 2013

In this study we investigated the possibility of preparing brewed brown rice makgeolli, a traditional Korean rice wine, under diverse conditions. For this purpose the physicochemical characteristics of makgeolli brewed at different temperatures, utilizing a variety of nuruks, the traditional Korean fermentation agent, were studied. The alcohol content was seen to be highest when brewing occurred at $30^{\circ}C$, with the nuruk TN producing 16.2%. At $20^{\circ}C$TN produced 14.1% alcohol content. The alcohol content was therefore higher, by about 2%, for $30^{\circ}C$ fermentations than $20^{\circ}C$ fermentations. Similarly, saccharifying activity was influenced by temperature and sugar content, with a higher activity seen at $30^{\circ}C$ than at $20^{\circ}C$. As the fermentations progressed acidification petered out, with titratable acidity being 0.50-0.67% in all end samples. On the Hunter L, a, b scale; the a value decreased slightly, while the b value increased steadily during the fermentation process. Measurements of total organic acids were highest at $30^{\circ}C$, with the nuruk AK, at about 550 mg%. The content of citric acid was the highest at $30^{\circ}C$, being 230-310 mg% in all samples. However, more lactic acid was detected at $20^{\circ}C$ than at $30^{\circ}C$. Total free amino acid was highest at $30^{\circ}C$, with TN at $8,605{\mu}g/ml$, AK at $6,083{\mu}g/ml$, and RJ at $2,381{\mu}g/ml$. Total free amino acid and essential amino acid was shown to be higher at $30^{\circ}C$ than at $20^{\circ}C$. The bioactive substance ${\gamma}$-aminobutyric acid was also higher at $30^{\circ}C$, with TN at $223{\mu}g/ml$. From all of these results, we surmise that brown rice makgeolli manufacturing conditions are optimal at $30^{\circ}C$ fermentation temperatures and using the nuruk TN for brewing vinegar. In addition, the nuruk used clearly affects the quality of brown rice makgeolli and an appropriate method to determine the best nuruk for various purposes should be pursued.

• Journal of Life Science
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• v.23 no.5
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• pp.698-702
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• 2013

It is known that black sticky rice with giant embryo (BSRGB, Milyang 263) and giant embryo rice (GER) contains higher levels of GABA than rice. Therefore, feeding BSRGB, GER, or rice freely to C57BL/6 mice with two-hour alcohol intake for 16 days was investigated. For two-hour alcohol intake, a repeated measure ANOVA (three treatment groups repeated across 16 days; 8 two-day blocks) yielded a significant group by block interaction (df=16, F=3.109, p=0.004). The independent t-test showed that significant suppression of two-hour alcohol intake was observed when subjects were administered with BSRGB, compared with the rice alone across all the two-day blocks (p<0.05). The paired t-test revealed that a significant suppression of two-hour alcohol intake was observed starting 4 to 16 days after freely feeding with BSRGB compared to before feeding. However, there is no significant difference in the two-hour alcohol intake observed between the before and after administration of rice. A repeated measure ANOVA revealed no significant group by block interaction for 22-hour water intake and body weight. However, a repeated measure ANOVA revealed a significant grouping by block interaction for food intake. These results indicate a change of two-hour alcohol intake is presumably caused by GABA, which is found in higher levels in BSRGB than in rice.