• The Korean Journal of Nuclear Medicine
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• v.36 no.4
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• pp.261-270
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• 2002

Purpose: Nicotinic acetylcholine receptors (nAChRs), which mediate excitatory neurotransmission, are known to participate in various neurophysiological functions. Severe losses of nAChRs have been noted in Alzheimer's and Parkinson's diseases. Therefore, noninvasive and quantitative imaging of nAChRs would offer a better understanding on the function of these receptors. In this study, $2-[^{18}F]fluoro-A85380\;([^{18}F]1)$, an ${\alpha}_4{\beta}_2$ nAChRs radioligand, was prepared using one HPLC purification and evaluated in mouse brain, and the results were compared with those in the literature. Materials and Methods: $[^{18}F]1$ was prepared by $[^{18}F]$fluorination of the iodo precursor followed by acidic deprotection and then purified by HPLC. Tissue distribution studies were performed in mouse brain at the indicated time points and the result was expressed as %ID/g. Inhibition studies were also carried out with pretreatment of various ligands. Results: One HPLC purification method gave the desired product in 15-20% radiochemical yield and with high specific activity ($38-55GBq/{\mu}mol$). Tissue distribution studies showed that $[^{18}F]1$ specifically labeled nAChRs in mouse brain with a high thalamus to cerebellum uptake ratio (13.8 at 90 min). Inhibition studios demonstrated selective binding of $[^{18}F]1$ to nAChRs, blocking the uptake of the $[^{18}F]1$ in nAChR-rich legions by selective ligands such as cytisine and nicotine which are well-known nAChRs agonists. Conclusion: This study demonstrated that the $[^{18}F]1$ produced by the method using one HPLC purification gave the results similar to those reported in the literature. Therefore, this synthetic method can be readily applied to the routine preparation of $[^{18}F]1$, a PET radioligand for ${\alpha}_4{\beta}_2$ nAChRs imaging.

• The Korean Journal of Nuclear Medicine Technology
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• v.19 no.1
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• pp.12-16
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• 2015

Purpose Principal component analysis (PCA) is a method often used in the neuroimagre analysis as a multivariate analysis technique for describing the structure of high dimensional correlation as the structure of lower dimensional space. PCA is a statistical procedure that uses an orthogonal transformation to convert a set of observations of correlated variables into a set of values of linearly independent variables called principal components. In this study, in order to investigate the usefulness of PCA in the brain PET image analysis, we tried to analyze C[11]-PIB PET image as a representative case. Materials and Methods Nineteen subjects were included in this study (normal = 9, AD/MCI = 10). For C[11]-PIB, PET scan were acquired for 20 min starting 40 min after intravenous injection of 9.6 MBq/kg C[11]-PIB. All emission recordings were acquired with the Biograph 6 Hi-Rez (Siemens-CTI, Knoxville, TN) in three-dimensional acquisition mode. Transmission map for attenuation-correction was acquired using the CT emission scans (130 kVp, 240 mA). Standardized uptake values (SUVs) of C[11]-PIB calculated from PET/CT. In normal subjects, 3T MRI T1-weighted images were obtained to create a C[11]-PIB template. Spatial normalization and smoothing were conducted as a pre-processing for PCA using SPM8 and PCA was conducted using Matlab2012b. Results Through the PCA, we obtained linearly uncorrelated independent principal component images. Principal component images obtained through the PCA can simplify the variation of whole C[11]-PIB images into several principal components including the variation of neocortex and white matter and the variation of deep brain structure such as pons. Conclusion PCA is useful to analyze and extract the main pattern of C[11]-PIB image. PCA, as a method of multivariate analysis, might be useful for pattern recognition of neuroimages such as FDG-PET or fMRI as well as C[11]-PIB image.

• Journal of the Korea Academia-Industrial cooperation Society
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• v.11 no.11
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• pp.4234-4243
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• 2010

Dementia such as poor concentration, anxiety and tension makes it hard to continue exercise in reality. For this, intermediate exercise is suggested in this study. And the study investigates the effects on senior fitness, cognitive function(MMSE-K) and daily living activity(ADL) by continuous exercise and intermittent exercise, which helps to provide proper exercise treatment to them. For this, female elderly patients at A dementia hospital in B Metropolitan city are selected and they have been diagnosed with possible Alzheimer's disease according to DSM-IV. Among them, six(6) are grouped for continuous exercise and five(5) for intermediate exercise, total 11 people are finally tested. They are given hand&foot exercise, Korean folk dance and band exercise three times a week for the total 12 weeks. The continuous exercise group does their exercise one time of 30 minutes a day while the intermediate exercise group for three times of each 10 minute a day. For the result, SPSS Ver. 18.0 is used to get mean value(M) and standard deviation(SD) and in order to verify the interaction effect between exercise group and time, two-way repeated ANOVA is applied and statistical significance level is set at .05. The result shows that there is significant difference in time between senior fitness and cognitive function. But there is no significant difference in group and time${\times}$group. And there is no significant difference in time, group and time${\times}$group for daily living activity. Continuous exercise group and intermediate exercise group both have the similar effects. That does not mean that intermediate exercise is the best for all people with dementia, but in terms of exercise time, intermittent exercise may be effective for patients of light dementia.

• Food Science and Preservation
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• v.15 no.5
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• pp.743-748
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• 2008

Amyloid $\beta$ peptide ($A{\beta}$) is known to increase oxidative stress in nerve cells, leading to apoptosis that is characterized by free radical formation and lipid peroxidation. Neurodegenerative diseases such as Alzheimer's disease (AD) are characterized by large deposits of $A{\beta}$ in the brain. In our study, neuronal protective effects of green tea, along with water activity (0.813), and leaf storage periods (fresh leaf, or leaf stored for up to 4 weeks) were investigated. We measured protective effects against $A{\beta}$-induced cytotoxicity in neuron-like PC12 cells. Powdered green tea was extracted with distilled water at $70^{\circ}C$ for 5 min, and this extract was freeze-dried and stored at $-20^{\circ}C$ until use. In cell viability assays using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), the fresh extract, and that obtained after 1 week of leaf storage, showed the best protective effects against $A{\beta}$-induced neurotoxicity. As oxidative stress causes membrane breakdown, the protective effect of green tea extracts was investigated using lactate dehydrogenase (LDH) and trypan blue exclusion assays. LDH release into the medium was inhibited (by 20-25%) in all tests. In addition, all green tea extracts (fresh, or stored before extraction for up to 4 weeks) showed better cell protective effects ($93.3{\pm}1.8-96.2{\pm}2.4$) than did vitamin C ($91.0{\pm}1.6$), used as a positive control. The results suggest that effectiveness of green tea extracts falls with prolonged leaf storage.

• Journal of the Korean Society of Radiology
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• v.15 no.6
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• pp.891-897
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• 2021

With the development of Amyloid PET Tracer, the accuracy of Alzheimer's diagnosis can be improved through the identification of beta-amyloid neurites. However, the long image acquisition time of 20 minutes can be difficult for the patient. PET/CT scans are sensitive to patient movement and may partially affect test results. In this study, we studied the proper image acquisition time without affecting the quantitative evaluation of the image through the list mode acquisition method according to the time of the distribution of radioactive drugs in the body. The list mode includes information about time compared to the existing frame mode, and it is easy to analyze data because it can reconstruct images about the time that researchers want. The research method obtained a reconstructed image by time using a list mode of 5min frame/bed, 10min frame/bed, 15min frame/bed, and 20min frame/bed to compare the difference between signal-to-pons take ratio (SNR) and lesion-to-pons uptake ratio (LPR) and the difference in reading time to obtain an appropriate image. As a result of quantitative analysis, when measuring in list mode, SUVmean values decreased in 6 regions of interest as the image acquisition time increased, but showed the largest difference in 5 min/bed images, followed by 10 min/bed and 15 min/bed. As a result, the difference in SUVmean values decreased. Therefore, it was found that SUVmean values at 15 min/bed did not differ enough to not affect image evaluation. There was no difference in LPR values. As a result of the qualitative analysis, there was no change in the reading findings according to the PET image acquisition time and there was no significant difference in the qualitative analysis score of the image reconstruction according to time. As a result of the study, there is no significant difference between 15 min/bed and 20 min/bed images during the ¹⁸F-flutemetamol PET/CT test, so it can be said that it is clinically useful to reduce the image acquisition time selectively using 15 min/bed via list mode depending on the patient's condition.

• Journal of Life Science
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• v.29 no.6
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• pp.747-753
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• 2019

Cognitive decline is characterized by reduced long-/short-term memory and attention span, and increased depression and anxiety. Such decline is associated with various degenerative brain disorders, especially Alzheimer's disease (AD) and Parkinson's disease (PD). The increases in elderly populations suffering from cognitive decline create social problems and impose economic burdens, and also pose safety threats; all of these problems have been extensively researched over the past several decades. Possible causes of cognitive decline include metabolic and hormone imbalance, infection, medication abuse, and neuronal changes associated with aging. However, no treatment for cognitive decline is available. In neurodegenerative diseases, changes in the gut microbiota and gut metabolites can alter molecular expression and neurobehavioral symptoms. Changes in the gut microbiota affect memory loss in AD via the downregulation of NMDA receptor expression and increased glutamate levels. Furthermore, the use of probiotics resulted in neurological improvement in an AD model. PD and gut microbiota dysbiosis are linked directly. This interrelationship affected the development of constipation, a secondary symptom in PD. In a PD model, the administration of probiotics prevented neuron death by increasing butyrate levels. Dysfunction of the blood-brain barrier (BBB) has been identified in AD and PD. Increased BBB permeability is also associated with gut microbiota dysbiosis, which led to the destruction of microtubules via systemic inflammation. Notably, metabolites of the gut microbiota may trigger either the development or attenuation of neurodegenerative disease. Here, we discuss the correlation between cognitive decline and the gut microbiota.

• Journal of Life Science
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• v.29 no.10
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• pp.1096-1103
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• 2019

Neuroinflammation is mediated by the activation of microglia and has been implicated in the pathogenesis of neurodegenerative disorders, such as Alzheimer's disease and Parkinson's disease. Therefore, the inhibition of neuroinflammation may be an effective solution to treat these brain disorders. Protaetia brevitarsis seulensis is an insect belonging to the order Coleoptera and inhabits Korea, China, Japan and Siberia. P. brevitarsis seulensis is an edible insect that can be consumed as a protein source for humans. It has been reported that P. brevitarsis seulensis contains useful bioactive substances for hepatoprotection and improving blood circulation, such as indole alkaloids. Microglia cells are the main source of proinflammatory cytokines and nitric oxide (NO) in the central nervous system, which Perform neuroimmune, inflammatory, and other neurobilogical functions. In this study, we investigated the anti-neuroinflammatory effects of P. brevitarsis seulensis ethanol extract (PBE) in activated microglia cells treated with lipopolysaccgarude (LPS, 100 ng/ml). As a result, PBE significantly inhibited NO production without cytotoxicity and decreased the expression levels of inducible NO synthase and cyclooxygenase-2. In addition, the production of inflammatory cytokine secreted by LPS was also reduced by PBE. These results suggest that PBE could be a good source of functional substances to prevent neuroinflammation and neurodegenerative diseases.

• Journal of Life Science
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• v.29 no.2
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• pp.173-180
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• 2019

Amyloid ${\beta}$-protein ($A{\beta}$) is the principal component of senile plaques characteristic of Alzheimer's disease (AD) and elicits a toxic effect on neurons in vitro and in vivo. Many environmental factors, including antioxidants and proteoglycans, modify $A{\beta}$ toxicity. It is worthwhile to isolate novel natural compounds that could prove therapeutic for patients with AD without causing detrimental side effects. In this study, we investigated the in vitro neuroprotective effects of the ethyl acetate fraction of methanol extract of Ophiophogon japonicas (OJEA fraction). We used an MTT reduction assay to detect protective effects of the OJEA fraction on $A{\beta}_{25-35}$-induced cytotoxicity to PC12 cells. We also used a cell-based ${\beta}$-secretase assay system to investigate the inhibitory effect of the OJEA fraction on ${\beta}$-secretase activity. In addition, we performed an in vitro lipid peroxidation assay to evaluate the protective effect of the OJEA fraction against oxidative stress induced by $A{\beta}_{25-35}$ in PC12 cells. The OJEA fraction had strong protective effects against $A{\beta}_{25-35}$-induced cytotoxicity to PC12 cells and was strongly inhibitory to ${\beta}$-secretase activity, which resulted in the attenuation of $A{\beta}$ generation. In addition, the OJEA fraction significantly decreased malondialdehyde (MDA) content, which is induced by the exposure of PC12 cells to $A{\beta}_{25-35}$. Our results suggested that the OJEA fraction contained active compounds exhibiting a neuroprotective effect on $A{\beta}$ toxicity.

• Korean Journal of Psychosomatic Medicine
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• v.29 no.2
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• pp.184-190
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• 2021

Objectives : Dementia is one of the most distressing mental health problems in the older population. Caregivers also experienced physical, psychological, and emotional stress from taking care of dementia patients. So, we developed program for supporting dementia caregiver and evaluated its efficacy on reducing caregiver burden. Methods : We provided 5 sessions of dementia caregiver supporting program to 30 caregivers who were taking care of dementia patient in their home. Program was held in Cheonan Center for Alzheimer's disease and other dementia that was established by Cheonan city government for supporting dementia patients and their caregivers. We evaluated caregiver burden using short Zarit burden inventory consisted of 12 items scoring 0 (no burden) to 4 (everyday burden) before and after program. We evaluated satisfaction of caregiver about program using satisfaction survey consisted of 10 items scoring 0 (very dissatisfy) to 4 (very satisfy) after program. Results : Mean age of caregiver was 61.9. 40.0% (n=12) of caregivers were spouse. 53.3% (n=16) of caregivers were son or daughter. Caregiver burden that was estimated by short Zarit burden inventory were significantly decreased after program (p<0.001). When each item was compared, 4 items (7, 10, 11 and 12) were significantly decreased after program (p=0.036, p=0.018, p=0.01, p=0.024). All mean scores of 10 items about satisfaction were over 3 meaning that participants generally satisfied to program. Conclusions : Our study suggested that dementia caregiver supporting program could reduce caregiver burden and provide satisfaction. Therefore, programs for supporting dementia caregivers might be important as well as treating dementia patients. So, we should be interested in developing and providing efficiently this kind of program to reduce caregiver burden.

• Korean Journal of Psychosomatic Medicine
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• v.30 no.2
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• pp.155-164
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• 2022

Objectives : A growing body of evidence links type 2 diabetes (T2D) with a neurodegenerative disease (ND) such as Alzheimer's disease and Parkinson's disease. The purpose of this study is to investigate the relationship between NDs and the development of T2D by comparing the incidence of T2D in a group of various NDs (ND group) and control group. Methods : A population-based 10-year follow-up study was conducted using the Korean National Health Information Database for 2002-2015. We used a retrospective cohort study design to investigate the association of ND with T2D occurrence. The study population included ND (n=8,814) and control (n=37,970) groups, all aged 60 years or over. The Kaplan-Meier method was used to estimate the risk of developing T2D as a function of time. Cox proportional hazards regression models were used to evaluate the relationship between ND and T2D. Results : T2D was developed in a significantly higher percentage of patients in the ND group (53.6%) than in the control group (44.7%). The ND group increased the risk of T2D (HR, 1.43; 95% CI, 1.38-1.47). About one-third of patients in both groups were additionally diagnosed with another ND before the occurrence of T2D during a 10-year follow-up period. When compared to those who did not have another ND during the follow-up period, the incidence of T2D in those who were additionally diagnosed with another ND was higher in both the ND and control groups. Conclusions : The ND group had about 1.4 times higher risk of developing T2D than the control group. Our results showed a positive association between ND and T2D.