• 생물정신의학
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• 제15권1호
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• pp.5-13
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• 2008

Objectives : It was the aim of the present paper to examine the impact of the apolipoprotein E(APOE) ${\varepsilon}4$ on cognitive performance in community-dwelling elderly samples with 'questionable dementia'. Methods : Total 295 samples who were diagnosed with 'questionable dementia' in the recent year and completed the Korean version of the Consortium Establish a Registry for Alzheimer's Disease(CERAD-K) neuropsychological assessment protocol, were recruited. The CDR test established score of 0.5. Genomic DNA was extracted from the venous blood and APOE genotyping was done in this group. Their cognitive performance was compared by the occurrence of the APOE ${\varepsilon}4$ allele. Results : The impact of ${\varepsilon}4$ allele was significant in the Word List Recall Test(WLRT, F=4.511, df=1, p=0.035). The 'young-old' group aged 75 years and under had a significantly lower performance on the Word List Recall Test(WLRT, F=5.090, df=1, p=0.015), but the 'old-old' group over 75 years of age had not significantly different performance on the all the item of tests in ${\varepsilon}4$+ allele group. Conclusion : The conclusion to be drawn here is that community-dwelling elderly samples with ${\varepsilon}4$ allele in 'questionable dementia' had a significantly lower performance on the Word List Recall Test in the CERAD-K neuropsychological test batteries and the effect was prominent in the 'young-old' age group.

• 동의신경정신과학회지
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• 제9궈1호
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• pp.1-24
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• 1998

The effects of Hyungbangjiwhangrang on the enhancement of learning and memory of AD model rats were studied with Morris water maze and radial arm maze. Sample group was electrolytically lesioned on nbM, and then daily treated with the medicine for two months. Control group with nbM lesion, and sham group with the sham operation were treated the vehicle for same duration. The following results were observed.1. As the learning trials of Morris water maze processed repeatedly, sham group achiened 201.64${\pm}$33.13 seconds in 1st trial, 153.14${\pm}$61.80 seconds in 2nd, 106.21${\pm}$46.81 seconds in 3rd, 76.64${\pm}$48.40 seconds in 4th, and 52.29${\pm}$38.25 seconds in 5th. The control group achieved 224.08${\pm}$29.16 in 1st trial, 191.77${\pm}$67.97 seconds in 2nd, 177.77${\pm}$65.44 seconds in 3rd, 140.92${\pm}$68.27 seconds in 4th, and 126.46${\pm}$79.15 seconds in 5th. The sample group achieved 223.36${\pm}$23.33 seconds in 1st trial, 215.86${\pm}$38.93 seconds in 2nd, 190.79${\pm}$51.57 seconds in 3rd, 155.79${\pm}$62.67 seconds in 4th, and 127.93${\pm}$62.11 seconds in 5th. Therefore, these data shows that all three groups were improved in learning capacity as trials were repeated, but the shame group showed prominent improvement in learning compared with the control group(p<0.05).2. In memory retention test of Morris water maze that counts the staying time in the target area, sham group stayed for 15.36${\pm}$5.39 seconds, the control group stayed for 5.54${\pm}$5.64 seconds, and the sample group stayed for 7.43${\pm}$6.09 seconds. The analysis of the memory retention data shows that the sham group marked more significant improvement stati- stically in memory retention compared with the control group(p<0.05).3. In the learning of radial arm maze, the number and rate of animals that arrive the learning criteria amounted 12 out of 14, 85.7% in sham group, 4 out of 13, 30.8% in the control group, and 10 out of 14, 71.4% in the sample group So, the sample group shows better learning capacity significantly compared with the control group(p<0.05). With the experimental results above, Hyungbangjiwhangtang can be supposed to have the improving effects on the learning and memory of AD rats induced by eletronical injury of nbM.

• 대한예방한의학회지
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• 제15권3호
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• pp.39-49
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• 2011

Objectives : Vascular dementia is the second common cause of dementia after Alzheimer's disease. It assumed that the ratio of prescription drugs on vascular dementia are quite different from each hospital in Western medicine or Oriental medicine, respectively. The aim of this research is to collect and analyze the ratio of prescription drugs on vascular dementia in Western medicine or Oriental medicine in university hospitals. Methods : We collected and analyzed the data related to prescriptions on vascular dementia in the department of neurology in three university hospitals(A, B, C) and in the department of internal medicine in two Oriental medicine hospitals(Daegu Haany Oriental Hospital, Dong Eui Oriental Hospital). Results : In the department of neurology in A university hospital, donepezil(69.1%), memantine(14.0%), rivastigmine(12.3%), galantamine(4.5%) were prescribed in order. In B university hospital, galantamine(57.8%) donepezil(33.3%), rivastigmine(6.7%), donepezil with memantine(4.4%) were prescribed. In C university hospital, donepezil(62.0%), rivastigmine(25.0%), galantamine(7.0%) memantine(6.0%) were prescribed. The average frequencies of prescribed medication in the department of neurology in A, B, C university hospitals were donepezil(54.8%), galantamine(23.1%), rivastigmine(14.7%), memantine(7.4%). In Oriental medicine hospitals, various prescriptions have been used for vascular dementia. Among them, Ansincheongnoetang (安神淸腦湯) and Gamijihangeumja(加味地黃飮子) were often prescribed in Daegu Haany Oriental Hospital, and Bojungikgitang(補中益氣湯) in Dong Eui Oriental Hospital, too. Conclusions : Cholinesterase inhibitors such as donepezil, galantamine, rivastigmine and NMDA receptor inhibitor like memantine have been used as a drug of choice for vascular dementia in all surveyed university hospitals. In oriental hospitals, various prescriptions have been used for vascular dementia.

• 생물정신의학
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• 제21권3호
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• pp.107-113
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• 2014

Objectives Restless legs syndrome (RLS) is a sleep disorder characterized by uncomfortable and unpleasant sensations in the legs and an urge to move the legs, usually at night. The aim of this study is to investigate the incidence of RLS in patients with late life depression and its influence on various clinical outcomes such as severity of depression, sleep quality, cognitive function, and quality of life and accordingly, to elucidate the clinical significance of RLS in patients with late life depression (LLD). Methods This study enlisted 170 depressive patients aged 65 years or older from an outpatient clinic. Structured diagnostic interviews were performed using the Korean version of the Mini-International Neuropsychiatric Interview. All patients completed the questionnaires, including the International RLS Severity Scale, the Korean version of Short-Form 36-Item Health Survey (SF-36), and the Pittsburgh Sleep Quality Index (PSQI). The severity of depression was evaluated by the Korean form of the Geriatric Depression Scale (KGDS) and the level of global cognition was assessed by the Mini-Mental State Examination in the Korean version of The Consortium to Establish a Registry for Alzheimer's Disease Assessment Packet (MMSE-KC). Results The incidence of RLS was 17.6% in LLD patients. RLS was more prevalent among the subjects with major depressive disorder (MDD) than those with minor depressive disorder or subsyndromal depressive disorder. The RLS group showed higher score in the KGDS than the Non-RLS group but the difference did not reach the statistical significance (p = 0.095, Student t-test). The mean PSQI score was significantly higher in the RLS group than in the Non-RLS group (p = 0.001, Student t-test). The MMSE-KC score was also lower in the RLS group than in Non-RLS group (p = 0.009, analysis of covariance). But, there was no difference in the score of SF-36 between the RLS group and the Non-RLS group. Conclusions RLS is common in LLD patients, especially in the patients with MDD and is associated with poor sleep quality and cognitive dysfunction, indicating that RLS is clinically significant in patients with LLD. Therefore, RLS should be considered as an important clinical issue in the management of LLD.

• 한국산학기술학회논문지
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• 제18권12호
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• pp.521-528
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• 2017

과도한 음주는 치매 및 알츠하이머 병과 같은 여러 신경계 질환을 일으키는 주요원인 중 하나로 알려져 있으며 이를 해결하기 위한 많은 노력인 진행 중이다. 또한, 홍삼은 신경 세포의 생존, 세포 자멸사의 억제 및 신경 세포의 신경 재생을 향상시키는 것으로 알려져 있다. 본 연구의 목적은 Rg3 풍부 고려홍삼 추출액(KRG)이 알코올 유발성 신경독성으로 인하여 일어나는 PC12 세포의 세포 사멸을 억제 할 수 있는지, 그리고 KRG가 caspase 매개 경로와 관련된 몇 가지 인자들을 어떻게 조절하는지 확인하는 것이다. 그 방법으로, 우리는 PC12 세포에서의 세포 생존율과 세포 사멸율은 EZ-Cytox 세포 생존율 측정 kit와 유세포 분석기로 측정하였고, 세포 자멸 관련 단백질(Bcl-2, Bax, caspase-3)의 발현 정도를 Western blot기법으로 측정하였으며, 측정된 결과의 유의성을 ANOVA 분석법으로 확인하였다. 그 결과, KRG는 Bcl-2의 발현을 증가시키고, Bid와 Bax 및 caspase-3 발현을 저해하였고, 이를 통해 알코올로 유도된 PC12 세포의 세포 사멸을 억제하였다. 이러한 결과를 통해, KRG에 의해 유도된 Bcl-2 발현의 증가와 Bid 및 Bax 발현의 하향 조절이 caspase-3 발현을 하향 조절하고, 결국 미토콘드리아 세포 사멸 경로를 억제한다는 것을 결론내릴 수 있었다. 본 연구는 향 후, KRG가 신경 보호제 후보로서 개발할 가치가 있음을 제시하였다.

• 동의신경정신과학회지
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• 제21권1호
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• pp.109-124
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• 2010

Objectives: This experiment was designed to investigate the effect of the InSamYangYoung-tang(Renshenyangrongtang) extract on $A{\beta}$-induced AD model. Methods: The effects of the InSamYangYoung-tang(Renshenyangrongtang) extract on neural damages of cultured PC12 cells induced by $A{\beta}$ were investigated. The effects of the InSamYangYoung-tang(Renshenyangrongtang) extract on neural damages of hippocampal and cortical neurons in the mouse induced by $\beta$-amyloid were investigated. Results: 1. $A{\beta}$ treatment into neuronal cells activated cell death pathway when analyzed by MTT assay and by histological analysis. Then InSamYangYoung-tang(Renshenyangrongtang) treatment improved cell survival to a similar level as in normal group. 2. $A{\beta}$ treatment increased caspase 3 protein levels but decreased phospho-Erk1/2 in neuronal cells. InSamYangYoung-tang(Renshenyangrongtang) treatment reversed the production levels of two proteins close to those in normal group. 3. $A{\beta}$ treatment induced the atrophy of neuronal cells in terms of neuronal processes and cell body shrinkage, but InSamYangYoung-tang(Renshenyangrongtang) greatly improved their morphology. 4. Neuroprotective activity, as observed in InSamYangYoung-tang(Renshenyangrongtang)-treated groups, was similarly observed in cells treated with galantamine which was used as a positive control. Moreover, overall recovery pattern by InSamYangYoung-tang(Renshenyangrongtang) was similar between cultured PC12 cells and in vivo hippocampal and cerebral cortical neurons in the mouse brain. Conclusions: This experiment shows that the InSamYangYoung-tang(Renshenyangrongtang) may play a protective role in neural tissues damaged by cytotoxic substances. Since neuronal damage seen in degenerative brains such as AD are largely unknown, the current data may provide possible insight into therapeutic strategies for AD treatments. InSamYangYoung-tang(Renshenyangrongtang) might be effective for the treatment of AD. Investigation into the clinical use of the InSamYangYoung-tang(Renshenyangrongtang) for AD is suggested for future research.

• 동의생리병리학회지
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• 제22권5호
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• pp.1202-1209
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• 2008

Peroxynitrite ($ONOO^-$), superoxide anion radical (${\cdot}\;{O_2}^-$) and nitric oxide (NO) are cytotoxic because they can oxidize several cellular components such as proteins, lipids and DNA. They have been implicated in the aging processes, and age-related diseases such as Alzheimer's disease, rheumatoid arthritis, cancer, diabetes, obesity and atherosclerosis. The aim of this study was to investigate the effects of Ojunghwan on the generation of peroxynitrite ($ONOO^-$), nitric oxide (NO) and superoxide anion radical (${\cdot}\;{O_2}^-$), and on the expression of $NF-{\kappa}B$-dependent inflammatory proteins in ob/ob mice. Mice were grouped and treated for 5 weeks as follows. Both the normal lean (C57/BL6J black mice) and control obese (ob/ob mice) groups have received the standard chow. The experimental groups were fed with a diet of chow supplemented with 30 and 90 mg Ojung-hwan per 1 kg of body weight for 14 days. For this study, the fluorescent probes, namely 2',7'-dichlorodihydrofluorescein diacetate (DCFDA), 4,5-diaminofluorescein (DAF-2) and dihydrorhodamine 123 (DHR 123) were used. Western blot was performed using anti-phospho $I{\kappa}B-{\alpha}$, $anti-IKK-{\alpha}$, $anti-NF-{\kappa}B$ (p50, p65), anti-COX-2, anti-iNOS, anti-VCAM-1 and anti-MMP-9 antibodies, respectively. Ojunghwan inhibited the generation of $ONOO^-$, NO and ${\cdot}\;{O_2}^-$ in the lipopolysaccharide (LPS)-treated mouse kidney postmitochondrial fraction in vitro. The generation of $ONOO^-$, NO, ${\cdot}\;{O_2}^-$ and $PGE_2$ were inhibited in the Ojunghwan-administered ob/ob mice groups. The GSH/GSSG ratio was decreased in the ob/ob mice, whereas that were improved in the Ojunghwan-administered groups. Ojunghwan inhibited the expression of $phospho-I{\kappa}B-{\alpha}$, $IKK-{\alpha}$, $NF-{\kappa}B$ (p50, p65), COX-2, iNOS, VCAM-1 and MMP-9 genes. These results suggest that Ojunghwan is an effective scavenger of $ONOO^-$, ${\cdot}\;{O_2}^-$, NO and $PGE_2$, and has an inhibitory effect on the expression of $NF-{\kappa}B$-dependent inflammatory genes in ob/ob mice. Therefore, Ojunghwan might be used as a potential therapeutic drug against the inflammation process and inflammation- related diseases.

• 인터넷정보학회논문지
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• 제17권2호
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• pp.59-65
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• 2016

색채 환경에 따라 인지반응의 상관관계를 분석한 결과가 다양한 산업분야에 적용되고 있다. 특히, 의학 분야에서 색채 환경기반 생체신호를 수집하여 환자 상태의 파악과 치료 그리고 뇌활동의 규명에 관련된 연구가 활발하게 진행되고 있다. 그러나 기존 연구들은 색채조명 또는 LED를 이용한 색채 환경을 구축하여 다양한 실험을 진행하고 있으나 다른 광원에 노출 되어 심리적인 영향을 주는 문제점을 갖고 있다. 따라서, 본 논문에서 제안하는 시스템은 HMD(Head-Mounted-Display)를 이용하여 피험자에게 완벽한 색채 환경조건을 제공하고자 한다. 그리고 인체반응정도 측정을 위해 기억력-주의력 테스트하는 동안 BMS(Bio-Medical-System)으로 생체정보를 수집하여 색채별 인체반응정도 측정뿐만 아니라 심리적인 변화에 대한 상관관계를 확인할 수 있는 시스템을 제안한다. 제안한 시스템을 통하여 수집하는 생체정보는 심전도(ECG), 호흡(Respiration), 산소포화도(SpO2), 임피던스(Bio-Impedance), 혈압(Blood-Pressure) 이며 데이터베이스에 저장한다. 이와함께, 인체의 인지반응을 측정하기위해 기억력-주의력 테스트는 앱으로 구현하여 색채 조건별 인지반응 정보를 측정하고 결과를 확인 할 수 있다. 제안한 시스템을 통하여 수집된 인체반응정보를 활용하여 생리학적 정보의 정량화하는 연구를 진행할 수 있으며, 색채 환경과 생리학적 정보의 상관관계를 분석하여 의학적 진단 및 치료에 응용이 될 것으로 기대한다. 향후 연구로 구축한 시스템을 통해 수집된 데이터를 분석 및 시각화 기능을 추가하고, 치매 질환의 예측 및 치료를 위한 시스템으로 확장하여 재활프로그램으로서의 유효성을 평가하고자 한다.

• 한국식품위생안전성학회지
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• 제31권1호
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• pp.59-66
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• 2016

Celastrol은 미역줄나무의 뿌리에서 얻은 추출물로 오래전부터 관절염 및 자가면역 같은 염증반응 질병들을 치료하기 위하여 쓰여져 왔다. 이외에도 많은 연구들에서 celastrol이 신경보호, 항산화 및 알츠하이머 치료에 사용될 수 있으며 특히, 암 치료에 효과적이라고 밝혀 졌다(Table 1). 따라서 많은 연구자들이 생리학적, 생화학적 및 면역학적 관점에서 celastrol의 항암효과를 규명하고자 노력을 기울이고 있으며, 다양한 관점에서 신호전달체계를 조절한다는 사실을 밝혀냈다(Fig. 1). 특히, celastrol은 $NF-{\kappa}B$를 억제함으로서 암의 발달 및 전이를 저해함을 물론, 암의 치료에 동반되는 면역 반응을 조절 할 수 있다(Fig. 2). 또한 세포사멸과 관계된 유전자들을 활성화 시키고, 항세포사멸 유전자들을 억제시킴으로서 세포 주기를 조절한다. 유전자 조절 외에도 heat shock protein과 같은 단백질의 변조와 자가소화작용(autophagy)를 유도한다. 이처럼 celastrol의 다양한 효과는 암의 성공적 치료에 한발 더 가까워지게 만든다. 이외에도 celastrol의 항 비만 효과가 알려지면서 향후 비만 및 비만과 연계된 암 환자들이 가질 수 있는 부작용, 오남용 및 비용절감 측면에서 좋은 결과를 나타낼 것이라 예상 된다. Celastrol의 다양한 기작이 밝혀짐에도 불구 하고 직접적인 결합 부위에 대한 연구 결과는 아직 없으며, 임상적용 하기에 앞서 다양한 동물모델 in vivo 실험이 필요하다. 또한 임상치료 시도에 있어 안전성을 확보 하기 위해서는 celastrol의 단기간 및 장기간의 효과에 대한 깊은 연구가 요구된다.

• 대한한의학회지
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• 제30권1호
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• pp.51-63
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• 2009

Objectives: Peroxynitrite ($ONOO^-$), superoxide anion radical (${\cdot}{O_2}^-$ and nitric oxide (NO) are cytotoxic because they can oxidize several cellular components such as proteins, lipids and DNA. They have been implicated in the aging processes, and age-related diseases such as Alzheimer's disease, rheumatoid arthritis, cancer, diabetes, obesity and atherosclerosis. The aim of this study was to investigate the $ONOO^-$, NO, ${\cdot}{O_2}^-$ scavenging and NF-${\kappa}B$ related anti-inflammatory activities of Sotosaja-hwan in ob/ob mice. Methods: Mice were grouped and treated for 5 weeks as follows. Both the normal lean (C57/BL6J black mice) and control obese (ob/ob mice) groups have received standard chow. The experimental groups were fed with a diet of chow supplemented with 30 and 90 mg Sotosaja-hwan per 1 kg of body weight for 14 days. For this study, the fluorescent probes, namely 2',7'-dichlorodihydrofluorescein diacetate (DCFDA), 4,5-diaminofluorescein (DAF-2) and dihydrorhodamine 123 (DHR 123) were used. Western blotting was performed using anti-phospho-$I{\kappa}B$-${\alpha}$, anti-IKK-${\alpha}$, anti-NF-${\kappa}B$ (p50, p65), anti-COX-2, anti-iNOS, anti-YCAM-1 and anti-MMP-9 antibodies, respectively. Results: Sotosaja-hwan inhibited the generation of $ONOO^-$, NO and ${\cdot}{O_2}^-$ in the lipopolysaccharide (LPS)-treated mouse kidney postmitochondrial fraction in vitro. The generation of $ONOO^-$, NO, ${\cdot}{O_2}^-$ and PGE2 were inhibited in the Sotosaja-hwan-administered ob/ob mice groups. The GSH/GSSG ratio was decreased in the ob/ob mice, whereas the ratio was improved in the Sotosaja-hwan-administered groups. Sotosaja-hwan inhibited the protein expression levels of phospho-$I{\kappa}B$-${\alpha}$, IKK-${\alpha}$, NF-${\kappa}B$ (p50, p65), COX-2, iNOS, YCAM-1 and MMP-9 genes. Conclusions: These results suggest that Sotosaja-hwan is an effective $ONOO^-$, ${\cdot}{O_2}^-$ and NO scavenger and has NF-kB related anti-inflammatory activity in ob/ob mice. Therefore, Sotosaja-hwan might be a potential therapeutic drug against the inflammation process and inflammation-related diseases.