• Biomolecules & Therapeutics
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• 제26권5호
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• pp.458-463
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• 2018

The phosphorylation of JNK is known to induce insulin resistance in insulin target tissues. The inhibition of JNK-JIP1 interaction, which interferes JNK phosphorylation, becomes a potential target for drug development of type 2 diabetes. To discover the inhibitors of JNK-JIP1 interaction, we screened out 30 candidates from 4320 compound library with In Cell Interaction Trap method. The candidates were further confirmed and narrowed down to five compounds using the FRET method in a model cell. Among those five compounds, Acebutolol showed notable inhibition of JNK phosphorylation and elevation of glucose uptake in diabetic models of adipocyte and liver cell. Structural computation showed that the binding affinity of Acebutolol on the JNK-JIP1 interaction site was comparable to the known inhibitor, BI-78D3. Our results suggest that Acebutolol, an FDA-approved beta blocker for hypertension therapy, could have a new repurposed effect on type 2 diabetes elevating glucose uptake process by inhibiting JNK-JIP1 interaction.

• Archives of Pharmacal Research
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• 제23권4호
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• pp.391-395
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• 2000

To establish the usefulness of oxytocin (OT) as an analgesic for women in delivery, the pharmacokinetic parameters and blood-brain barrier (BBB) permeability of [$^3H$] OT were obtained using an intravenous injection technique or the internal carotid artery perfusion/capillary depletion (ICAP/CDM) method. Brain uptake of OT was similar to that of sucrose, plasma space marker, indicating that OT has a poor BBB permeability. Moreover, the analgesic effects of OT injected through the jugular vein on nociception were evaluated by the tail-flick method. The antinociceptive effects of OT injected at a dose of 0.2 ${m}g/kg$or 2 ${m}g/kg$ were dose-dependent. In addition, the analgesic effects of OT on the CNS were unaffected by naloxone, a m-receptor antagonist. In a similar manner to the opioid system, OT may play a modulatory role in antinociception.

• 대한핵의학회지
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• 제38권3호
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• pp.272-273
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• 2004

We experienced a case with meningioma showing false positive I-131 uptake. A 55-years old female patient underwent high dose (150 mCi) radioactive iodine therapy to ablate remnant tissue after total thyroidectomy for papillary thyroid cancer. in addition to intense tracer uptake in thyroid bed, there was mild but focal abnormal uptake in left frontal lobe of the brain on post-therapy I-131 whole body scan. Subsequent brain MR imaging showed single mass lesion in left frontal lobe and the mass was resected under the impression of brain metastasis of thyroid carcinoma. Pathologic report confirmed meningioma from the surgical specimen.

• The Korean Journal of Physiology and Pharmacology
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• 제1권4호
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• pp.367-376
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• 1997

The effect of an organic peroxide, t-butylhydroperoxide (t-BHP), on glutamate uptake was studied in synaptosomes prepared from cerebral cortex. t-BHP inhibited the $Na^+-dependent$ glutamate uptake with no change in the $Na^+-independent$ uptake. This effect of t-BHP was not altered by addition of $Ca^{2+}$ channel blockers (verapamil, diltiazem and nifedipine) or $PLA_2$ inhibitors (dibucaine, butacaine and quinacrine). However, the effect was prevented by iron chelators (deferoxamine and phenanthroline) and phenolic antioxidants (N,N'-diphenyl-phenylenediamine, butylated hydroxyanisole, and butylated hydroxytoluene). At low concentrations (＜1.0 mM), t-BHP inhibited glutamate uptake without altering lipid peroxidation. Moreover, a large increase in lipid peroxidation by $ascorbate/Fe^{2+}$ was not accompanied by an inhibition of glutamate uptake. The impairment of glutamate uptake by t-BHP was not intimately related to the change in $Na^+-K+-ATPase$ activity. These results suggest that inhibition of glutamate uptake by t-BHP is not totally mediated by peroxidation of membrane lipid, but is associated with direct interactions of glutamate transport proteins with t-BHP metabolites. The $Ca^{2+}$ influx through $Ca^{2+}$ channel or $PLA_2$ activation may not be involved in the t-BHP inhibition of glutamate transport.

• 약학회지
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• 제47권4호
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• pp.224-229
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• 2003

We have investigated the transport characteristics of synthetic antioxidant and free radical scavenger, $\alpha$-phenyl-n-tert-butyl nitrone (PBN) at the blood-brain barrier (BBB) by in vitro uptake study in conditionally immortalized rat brain capillary endothelial cell line (TR-BBB). Also, the efflux of PBN from brain to blood is estimated using the brain efflux index (BEI) method. Choline is a charged organic cation, including nitrogen-methyl group and shows the carrier-mediated distribution to the brain. [$^3$H]Choline uptake by TR-BBB cells was significantly inhibited by PBN with $IC_{50}$/ of 1.2 mM, which appears to be due to similar structures between choline and PBN. And, PBN was microinjected into Par2 of the rat brain by BEI method, and was eliminated from the brain with an apparent elimination half-life of about 2 min. Also, [$^3$H]choline efflux was significantly inhibited by PBN using BEI method. In conclusion, the efflux transport of PBN takes place across the BBB and PBN may be transported into the brain and eliminated from the brain by BBB choline transporter.

• Journal of Nutrition and Health
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• 제3권2호
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• pp.101-106
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• 1970

Radioactive Phosphorus $(^{32}P)$ was administered intramuscularlly to the newly hatched chicken in the purpose of determination of the uptake and the distribution, as related to sex and hour differences of the several organs of the bodies. $2\;{\mu}\;of\;^{32}P$ was administered to each chick, and the distribution of 32P was observed in 1 hour and 24 hours after administration. In this experiment 80 heads of chicken were used(40 chicken were one day and 40 chicken were 7 days old) and the results obtained as follows: 1. The tissue showed an uptake rate of $^{32}P$ dose per 100 milligram of tissue in one day old chicken, with the following sequence: Males (1 hour): Femur. Liver. G., Muscle. Testis. Brain (24 hour): Femur, Testis, Gastrocnemius Muscle, Liver, Brain. Female(1 hour): Femur, Liver, Gastronemius Muscle, Ovary, Brain. (24 hour): Femur, Liver, Gastrocnemius Muscle, Ovary, Brain. 2. In 1 hour, the uptake rate of $^{32}P$ of the tissues showed significant difference between the male and the female except the gastrocnemius muscle and the brain in one day old group, but they were no significance except the testis and ovary after 24 hours. 3. The distribution of $^{32}P$ of the tissues exhibited higher in 1 hour than in 24 hours except the femur, the brain of the male and female, the brain and gastrocnemius muscle of the female in one day old group. 4. The tissue showed an uptake rate of $^{32}P$ dose per 100 miligram of tissue in 7days old chicken, with the following sequence: Male (1 hour): femur, liver, gastrocmenius muscle, testis, brain. (24 hour): femur, testis, gastrocmenius muscle, liver, brain. Female(1 hour): femur, liver, gastrocmenius muscle, ovary, brain. (24 hour): femur, ovary, liver, gastrocmenius muscle, brain. 5. The distribution of $^{32}P$ of the tissues showed no significant difference between the male and the female except the testis and ovary after 24 hours in 7 days old chicken group. 6. The distribution of $^{32}P$ the tissues exhibited higher in 1 hour in 24 hours except the femur, the brain of the male and the female, the brain and the ovary of the female in 7 days old chicken group.

• Journal of Pharmaceutical Investigation
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• 제20권4호
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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.

• The Korean Journal of Physiology and Pharmacology
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• 제1권2호
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• pp.127-133
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• 1997

Lithium remains the most widely used therapeutic agent for bipolar affective disorder, particularly mania. Although many investigators have studied the effects of lithium on abnormalities in monoamine neuro-transmitter as a pathophysiological basis of affective disorder, the action mechanism of lithium ion remains still unknown. To explore the action mechanism of lithium in the brain, we examined the effects of lithium on the extrasynaptosomal concentrations of catecholamines and their metabolites. Synaptosomes were prepared from the rat forebrains and assays of catecholamines and metabolites were made using HPLC with an electrochemical detector. Lithium of 1mM decreased the extrasynaptosomal concentrations of NE from the control group of $3.07{\pm}1.19$ to the treated group of $0.00{\pm}0.00$ (ng/ml of synaptosomal suspension) but not that of DHPG. It can be suggested that lithium increases synaptosomal uptake of NE. Increased intraneuronal uptake of NE would decrease neurotransmission and extraneuronal metabolism of NE. Because increased brain NE metabolism and neurotransmission have been suggested as important components in the pathophysiology of bipolar affective disorder, especially mania, lithium-induced increase of intraneuronal NE uptake can be suspected as an action mechanism of therapeutic effect of lithium in manic patient, possibly in bipolar affective disorder.

• 대한치매학회지
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• 제17권3호
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• pp.90-99
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• 2018

Background and Purpose: To explore anatomic substrate of specific wandering patterns in patients with Alzheimer's disease (AD) by performing positron emission tomography with $^{18}F$ fluorodeoxyglucose positron emission tomography (FDG PET). Methods: Drug-naïve AD patients with wandering (n=80) and without wandering (n=262) were recruited. First, the specific pattern of wandering type was operationally classified according to specific wandering score and clinical assessment. Second, brain FDG PET was performed and fluorodeoxyglucose (FDG) uptake differences of specific brain regions according to wandering patterns were compared to those of non-wanderers. Results: In patients with pacing pattern, FDG PET showed significant lower FDG uptake in both middle cingulum and left putamen cluster compared to non-wanderers. The right precuneus and supplementary motor area in patients with random pattern and left calcarine sulcus, right calcarine sulcus, right middle cingulum, and right post central gyrus in patients with lapping pattern had significantly lower FDG uptake compared to non-wanderers. Conclusions: This study showed that wandering in patients with AD had three distinct patterns. These specific patterns showed significant lower FDG uptake in specific brain areas compared to non-wanderers.

• Journal of Korean Neurosurgical Society
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• 제49권5호
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• pp.278-283
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• 2011

Objective : The purpose of this study was to evaluate whether $^{18}F$-fluorodeoxyglucose positron emission tomography (FOG-PET) can be used to assess the therapeutic response of brain abscess. Methods : A study was conducted on 10 consecutive patients with brain abscess, Magnetic resonance imaging (MRI) with diffuse-weighted imaging (DWI) was performed at 3 and 6 weeks after surgical treatment and intravenous antibiotics therapy and FOG-PET at 6 weeks after treatment. The extent of the abscess, signal changes on MRI, and FOG-PET standardized uptake values were analyzed and correlated with the response to therapy. Results : Aspiration or craniotomy with excision of the abscess followed by intravenous antibiotics for 6-8 weeks resulted in good recovery with no recurrence. In 10 patients, two had low signal intensity on the DWI; one had no uptake on FOG-PET imaging after 6 weeks antibiotics and discontinued intravenous treatment, but the other patient had diffuse, increased uptake on FOG-PET imaging after 6 weeks antibiotics and underwent an additional 2 weeks of intravenous antibiotics. The remaining eight patients had high signals on the DWI. Four had no uptake on FOG-PET imaging and the treatment period varied from 6 to 8 weeks (mean, 6.75 weeks). Among the other four patients, FOG was accumulated in a diffuse or local area corresponding to a high signal area within the DWI and 2 weeks of intravenous antibiotics was added. Conclusion : MRI plus FOG-PET improved the accuracy of assessing therapeutic responses to antibiotics treatment of brain abscess and aided in optimizing therapy.