• Journal of Pharmaceutical Investigation
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• v.20 no.4
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• pp.223-228
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• 1990

The contribution of endogenous transport systems to the blood-brain barrier (BBB) transport of basic and acidic drugs was studied by using a carotid injection technique in rats and an isolated bovine cerebrovascular disease state were compared between the normotensive rats (WKY) and stroke-prone spontaneously hypertensive rats (SHRSP) which have been well established as an animal model with pathogenic similarities to humans. Basic drugs such as eperisone, thiamine and scopolamine inhibited, in a concentration dependent manner the in vivo uptake of $[{^3}H]choline$ through BBB, whereas amino acids and acidic drugs such as salicylic acid and valproic acid did not inhibit the uptake. The uptake of $[^3H]choline$ by B-CAP increased with time and showed a remarkable temperature dependency. The uptake of $[^3H]choline$ by B-CAP showed the very similar inhibitory effects as observed in the in vivo brain uptake, and was competitively inhibited by a basic drug, eperisone. The in vivo BBB uptakes of $[^3H]acetic$ acid and $[^{14}C]salicylic$ acid were dependent on pH of the injectate and the concentration of drugs. Several acidic drugs such such as salicylic acid, benzoic acid and valproic acid inhibited the in vivo uptake of $[^3H]acetic$ acid, whereas amino acid, choline and a basic drug such as eperisone did not inhibit the uptake. The uptake of acetic acid by B-CAP was competitively inhibited by salicylic acid. The permeability surface area product (PS) through BBB for $[^3H]choline$ in SHRSP was significantly lower than that in WKY. The concentration of choline in the brain dialysate in SHRSP was about half of that in WKY, while no significant difference was observed in the plasma concentration of choline between SHRSP and WKY. No significant difference was observed in the transport of monocarboxylic acids, glucose and neutral amino acid through BBB between SHRSP and WKY. From these results, it was concluded that BBB transport system of choline contributes to the transport of basic drugs through BBB, that acidic drugs can be transported via a moncarboxylic acid BBB transport system and that the specific dysfuntion of the BBB choline transport in SHRSP was ascribed to the reduction of the maximum velocity of choline concentration in the brain interstitial fluids.

• Journal of Life Science
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• v.31 no.8
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• pp.729-735
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• 2021

Type 2 diabetes occurs when there is an abnormality in the tissue's ability to absorb glucose. Glucose uptake and metabolism by insulin are the basic mechanisms that maintain blood sugar. Glucose uptake goes through various signaling steps initiated by the binding of insulin to receptors on the cell surface. In line with the foregoing, the purpose of this study was to investigate the effect of 2,7-phloroglucinol-6,6-bieckol (PHB), an active compound isolated from Ecklonia cava, on glucose uptake in 3T3-L1 adipocytes. Notably, PHB increased glucose uptake in a dose-dependent manner owing to the enhanced glucose transporter type 4 (GLUT4) expression in the plasma membrane of 3T3-L1 adipocytes. These effects of PHB were attributed to the phosphorylation of insulin receptor substrate-1 and protein kinase B (PKB or AKT), as well as to the phosphoinositide 3-kinase (PI3K) activation in the insulin signaling pathway. PHB also stimulated 5' AMP-activated protein kinase (AMPK) phosphorylation and activation. The phosphorylation and activation of the PI3K/AKT and AMPK pathways by PHB were identified using wortmannin (a PI3K inhibitor) and compound C (an AMPK inhibitor). In this study, we showed that PHB can increase glucose uptake in 3T3-L1 adipocytes by promoting GLUT4 translocation to the plasma membrane via the PI3K and AMPK pathways. The results indicate that PHB may help improve insulin sensitivity.

• Nutrition Research and Practice
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• v.16 no.1
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• pp.33-45
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• 2022

BACKGROUND/OBJECTIVES: Ginseng extract (GSE) and taurine (TR) are widely used antifatigue resources in functional foods. However, the mechanism underlying the antifatigue effects of GSE and TR are still unclear. Hence, we investigated whether GSE and TR have synergistic effects against fatigue in mice. MATERIALS/METHODS: L6 cells were treated with different concentrations of TR and GSE, and cell viability was determined using 2-(4-iodophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium. Oxidative stress was analyzed by immunocytochemistry using MitoTracker^TM Red FM and an anti-8-oxoguanine antibody. Respiratory gas analysis was performed to investigate metabolism. Expression of an activated protein kinase was analyzed using immunohistochemistry. Gene expression of cluster of differentiation 36 and pyruvate dehydrogenase lipoamide kinase isozyme 4 was measured using reverse transcription-polymerase chain reaction. Mice were orally administered TR, GSE, or their combination for 30 days, and then fatigue-related parameters, including lactate, blood urea nitrogen, and glycogen, were measured after forced swimming. RESULTS: TR and GSE reduced oxidative stress levels in hydrogen peroxide-stimulated L6 cells and enhanced the oxygen uptake and lipid metabolism in mice after acute exercise. After oral administration of TR or GSE for 30 days, the fatigue-related parameters did not change in mice. However, the mice administered GSE (400 mg/kg/day) alone for 30 days could swim longer than those from the other groups. Further, no synergistic effect was observed after the swimming exercise in mice treated with the TR and GSE combination for 30 days. CONCLUSIONS: Taken together, our data suggest that TR and GSE may exert antifatigue effects in mice after acute exercise by enhancing oxygen uptake and lipid oxidation.

• Nuclear Medicine and Molecular Imaging
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• v.43 no.5
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• pp.495-498
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• 2009

Brown tumor is the benign bone lesion consists of woven bone and fibrous tissue without matrix, which develop due to chronic excessive osteoclastic activity such as hyperparathyroidism. Usually they appear with normal uptake or occasionally focally increased uptake on bone scan. We present a case with brown tumor shown more increased uptake and more number of lesions on bone scan after parathyroidectomy, and lesser increased uptake on serial bone scans without any other treatment through several months. This finding is thought to be similar to 'flare phenomenon' which is occasionally seen after treatment of metastatic bone lesions of malignant cancer, and may represent curative process of brown tumor with rapid normal bone formation.

• BMB Reports
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• v.52 no.7
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• pp.457-462
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• 2019

[18F]Fluorodeoxyglucose (FDG) PET/CT imaging has been widely used in the diagnosis of malignant tumors. ATPase family AAA domain-containing protein 2 (ATAD2) plays important roles in tumor growth, invasion and metastasis. However, the relationship between [18F]FDG accumulation and ATAD2 expression remains largely unknown. This study aimed to investigate the correlation between ATAD2 expression and [18F]FDG uptake in lung adenocarcinoma (LUAD), and elucidate its underlying molecular mechanisms. The results showed that ATAD2 expression was positively correlated with maximum standardized uptake value ($SUV_{max}$), total lesion glycolysis (TLG), glucose transporter type 1 (GLUT1) expression and hexokinase2 (HK2) expression in LUAD tissues. In addition, ATAD2 knockdown significantly inhibited the proliferation, tumorigenicity, migration, [18F]FDG uptake and lactate production of LUAD cells, while, ATAD2 overexpression exhibited the opposite effects. Furthermore, ATAD2 modulated the glycometabolism of LUAD via AKT-GLUT1/HK2 pathway, as assessed using LY294002 (an inhibitor of PI3K/AKT pathway). In summary, to explore the correlation between ATAD2 expression and glycometabolism is expected to bring good news for anti-energy metabolism therapy of cancers.

• 한국지구물리탐사학회:학술대회논문집
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• 2003.11a
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• pp.479-492
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• 2003

Wheat, barley, rye, and maize were grown in field and pot experiments at various non-contaminated soils in order to establish uptake rates for added selenate, and to find baseline concentrations for various soil types. Edible parts (grains) and stalks of the crops were analyzed separately for Se, as well as for Ca, Cu, Fe, Mn, P, S, and Zn. The addition of Na-selenate in admixture with the NPK 20:8:8 fertilizer had no influence on the composition of the other elements investigated. The proportions of added nitrate: selenate, and sulfate:selenate were kept constant. The Se- uptake rate differed among the cereals tested, it was highest for winter wheat. Utilization of added Se in the field ranged from $0,4-4,7\%$, and and in the pots from $3,3-5,4\%$, it was markedly lower in clay soil. Whereas P and Zn were preferably found in the grains, Ca-Fe-Mn-S got enriched in the stalks. For the fields, the location had some influence upon Fe, Mn, and Zn, whereas it was not important for P, S, Cu, and strikingly, Ca. Pot and field experiments on similar soils led to different results, except for P and S. Maize (whole grains) was significantly lower in Ca, Cu, and Mn, and might even cause trace element deficiencies, if exclusively fed. Few correlations between the trace elements investigated led to the conclusion that most element contents were governed by plant metabolism. Variations of mobile Fe in the soils were balanced by uptake into the stalks. The data are compared with data from other presumably non-contaminated sites.

• Journal of Biomedical Engineering Research
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• v.32 no.1
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• pp.55-60
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• 2011

Although sound intensity is considered as one of important factors in auditory processing, its neural mechanism in auditory neurons with limited dynamic range of firing rates is still unclear. In this study, we examined the effect of sound intensity adaptation on the change of glucose metabolism in a rat brain using [F-18] micro positron emission tomography (PET) neuroimaging technique. In the experiment, broadband white noise sound was given for 30 minutes after the [F-18]FDG injection in order to explore the functional adaptation of rat brain into the sound intensity levels. Nine rats were scanned with four different sound intensity levels: 40 dB, 60 dB, 80 dB, 100 dB sound pressure level (SPL) for four weeks. When glucose uptake during the adaptation of a high intensity sound level (100 dB SPL) was compared with that during adaptation to a low intensity level (40 dB SPL) in the experiment, the former induced a greater uptake at bilateral cochlear nucleus, superior olivary complexes and inferior colliculi in the auditory pathway. Expectedly, the metabolic activity in those areas linearly increased as the sound intensity level increased. In contrast, significant decrease interestingly occurred in the bilateral auditory cortices: The activities of auditory cortex proportionally decreased with higher sound intensities. It may reflect that the auditory cortex actively down-regulates neural activities when the sound gets louder.

• YAKHAK HOEJI
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• v.33 no.1
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• pp.1-9
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• 1989

We have recently reported that $Mg^{++}-deficiency$ showed endothelium dependent relaxation in isolated canine coronary arteries precontracted with $PGF_{2{\alpha}}$. To differentiate the release of EDRF or $PGI_2$ from the endothelium cells as the cause of vasorelaxation by $Mg^{++}-deficiency$, effects of several inhibitors of arachidonic acid metabolism on the relaxation by $Mg^{++}-deficiency$ were evaluated and also compared with that of acetylcholine. Ibuprofen and tranylcypromine ($10{\mu}M$), an inhibitor of cyclo-oxygenase and $PGI_2$ synthetase, respectively, did not effect on $Mg^{++}-free$ induced vasorelaxation. Pretreatment of quinacrine ($10{\mu}M$), an inhibitor of phospholipase $A_2$ and also $Ca^{++}$ uptake, blocked vasorelaxation by $Mg^{++}-free$. But trifluoperazine ($10{\mu}M$), which is about as potent as quinacrine in the inhibition of $Ca^{++}$ uptake, did not effect on $Mg^{++}-deficiency$ induced vasorelaxation. NDGA ($10{\mu}M$), an inhibitor of lipoxygenase, completely restored $Mg^{++}-free$ induced vasorelaxation, even though pretreatment of that was not blocked which might be due to the characteristics of vasorelaxation of NDGA itself. Pretreatment of methylene blue ($10{\mu}M$), which is known as a inhibitor of EDRF through the blocking effect of guanylate cyclase, completely blocked vasorelaxation by $Mg^{++}-free$ as well as acetylcholine ($0.1{\mu}M$). Acetylcholine-induced dose response curve was also antagonized by pretreatment of quinacrine ($10{\mu}M$), but not by ibuprofen, tranylcypromine and NDGA. These results appear to suggest that $Mg^{++}-free$ induced vasorelaxation was mediated by the release of EDRF through the activation of phospholipase $A_2$ and noncyclo-oxygenase on arachidonate metabolism.

• The Journal of Korean Medicine
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• v.27 no.3 s.67
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• pp.169-177
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• 2006

Objective: The aim was to study experimentally the effects of Dioscorea bulbifera L. induced by sodium levothyroxine. Methods: Sprague-Dawley rats were separated into four groups. Except for the normal group, the other three were treated with sodium levothyroxine $160{\mu}g/kg$ for 5 days. Among the three groups, two (except the control) were treated with Dioscorea bulbifera L. extract of 0.75g/kg (sample A) or 1.5g/kg (sample B). $T_3-uptake,\;T_3,\;T_4$, TSH, total cholesterol, glucose, ALP, AST, ALT, tree fatty acids, $\beta-lipoprotein$, and change in the serum of rats were measured after medication with solid extract of Radix Scrophulariae. Results: $T_4$ concentration and $T_3-uptake$ level decreased in sample A and B compared to controls. $T_3$ concentration decreased but not statistically meaningful. Considering lipid metabolism, only free fatty acid level was significantly reduced glucose level also significantly decreased in sample B. Serum AST, ALT and ALP levels were slightly elevated but there was no meaning statistically, which doesn't mean Dioscorea bulbifera L. has liver toxicity because the quantity of the extract perhaps couldn't reach the minimal dose causing liver toxicity, which according to an article was 60g. Body weight significantly increased in comparison to controls. Conclusion: These results suggest that Dioscorea bulbiftra L. lowers excess thyroid hormone and increased metabolism, resulting in improvement of hyperthyroid state.

• Journal of Radiopharmaceuticals and Molecular Probes
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• v.4 no.2
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• pp.57-64
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• 2018

${\omega}-[^{18}F]$-Fluorohexadecanoic acid (FHA) has been used for imaging of fatty acid metabolism of myocardium. To increase retention of radiolabeled fatty acid by blocking ${\beta}$-oxidation, methyl branched analogues have been used. In this experiment, we tried to synthesize 18F-labeled ${\alpha}-$, ${\beta}-$ and ${\omega}-FHA$ for imaging of the myocardial fatty acid metabolism. We synthesized ${\alpha}-$, ${\beta}-$ and ${\omega}$-mesylated methyl hexadecanoates and labeled with $^{18}F$ by reacting with $[^{18}F]$TBAF in acetonitrile at $80^{\circ}C$ for 10 min. Methyl ester group was removed by 1 M NaOH at $80^{\circ}C$ for 5 min. The yields of ${\alpha}-[^{18}F]$ and ${\omega}-[^{18}F]FHA$ were 25.5 and 45.5%, respectively [EOS]. However, ${\beta}-[^{18}F]FHA$ was not labeled at all due to a fast elimination reaction. The biodistribution study in ICR-mice showed that ${\omega}-[^{18}F]FHA$ has higher myocardial uptake and lower liver uptake than ${\alpha}-[^{18}F]FHA$. The electron-withdrawing effect of fluorine at ${\alpha}-$ position is believed to be the major factor affecting the biodistribution.