• Journal of Oriental Neuropsychiatry
• /
• v.16 no.1
• /
• pp.43-66
• /
• 2005

Object : This study was designed to asses the protective effects of Kunneo tang on cognitive decline of the patients with early DAT. Method : Before administered with Kunneotang, 16 patients with early DAT were measured by auditory ERP, MMSE-K and K-DRS. During 12 months the patients with early DAT were administered with Kunneotang. After 12months the patients were measured by the same examinations again. Result : 1. The total score of MMSE-K decreased but it was not significant. 2. The total score of K-DRS increased but it was not significant. Among the five criteria(attention, memory, initiation/perseveration, construction, conceptualization), Initiation/perseveration score signifcantly decreased and there were no significant differences in the other scores. But, memory mean score had a tendency to increase. 3. The latency of ERP P300 component increased but it was not significant and the amplitude of ERP P300 component showed the significant difference. Conclusion : The results suggest that Kunneotang may have protective effects on cognitive decline in the patients with early DAT.

• Journal of Technologic Dentistry
• /
• v.27 no.1
• /
• pp.19-25
• /
• 2005

Ti6Al4V alloy have been mainly used as implant materials. Ti-6Al-4V alloy instead of pure Ti is being widely used as biomaterials has some characteristics such as high fatigue strength, tensile strength. But it has been reported recently that vanadium component expresses cytotoxicity and carcinogenicity and aluminium component is related with dementia of Alzheimer type. In order to overcome their detrimental effects, $\beta$-phase stabilizer Nb was chosen in the present study, in addition Ta and Hf were added to Ti-40wt.%Nb alloy to improve its mechanical properties. This paper was described the influence of heat treatment of Ti-40Nb alloys with 2wt%Ta, 2wt%Hf on the mechanical properties. Specimens of Ti alloys were melted in vacuum arc furnace and homogenized at 1050$^{\circ}C$ for 24 hr. and then were aged after solution heat treat at $\alpha+\beta$ and $\beta$ regions. The mechanical properties of Ti alloys were analysed by hardness test, tensile test, elongation test and SEM test. The results can be summarized as follows: 1. The mechanical properties Ti-40wt.%Nb were improved when 2wt.% Ta and 2wt.%Hf were added. 2. The higher tensile strength value and elongation at solution heat treat was higher than solution heat treat and then were aged.

• YAKHAK HOEJI
• /
• v.46 no.3
• /
• pp.208-212
• /
• 2002

Dehydroevodiamine HCl (DHED), which is a component separated from Evodia rutaecarpa Bentham, has novel anticholinesterase and antiamnesic activities in the scopolamine-induced amnesia model. Several studies suggest that DHED might be an effective drug for the Alzheimer's disease and the vascular type of dementia. In order to evaluate the mutagenic potential of DHED, Salmonella typhimurium reversion assay, chromosomal aberration test on Chinese hamster lung cells, in vivo micronucleus assay using mouse bone marrow cells, and comet assay were performed. DHED did not increase the number of revertant in the reverse mutation test using Salmonella typhimurium TA1535, TA1537, TA98, TA100. DHED HCl, at concentration of 5 and 10 $\mu\textrm{g}$/mι, increased the number of chromosome aberrated Chinese hamster lung cells with 5 and 10％, respectively. In mouse micronucleus test, no significant increase in the occurrence of micronucleated polychromatic erythrocyte was observed in ICR mice orally administered with DHED. DHED was tested for ability to induce genotoxic effect in L5178Y cells (mouse lymphoma cells) using the single cell gel electrophoresis assay (comet assay). In comet assay, tail moment did not increase in L5178Y cells treated with 10, 100, 300 $\mu$M DHED.

• Korean Journal of Biological Psychiatry
• /
• v.3 no.2
• /
• pp.170-180
• /
• 1996

Lowered immune function in the senile dementia patients may be related to the abnormal metabolism of amyloid precursor protein(APP). To investigate the passibility of an abnormal metabolism of APP in lymphocytes and the possible role of APP in the activation of lymphocytes in senile dementia patients, immunohistochemical study of rat spleen and fluorescence activated cell sorter analysis(FACS) of human lymphocytes with the specific antigen far each lymphocyte and double fluorescent marker with antibody to APP were performed. After stimulating lymphocyte with phytohemagglutinin(PHA), APP mRNA and protein were extracted and quantitfied and the influence of ${\beta}$-amyloid protein($A{\beta}$) specific antibody on lymphocyte division was investigated. In spleen, the majority of cells showing $A{\beta}$ immunoreactivity was found in the T-sell dependent zone. FACS indicated that around 90% $CD_4(+)$ T-cells and 60% of $CD_8(+)$ T-sell were immunoreactive to $A{\beta}$ specific antibody(mAb 4G8). Northern blot analysis shows that lymphocyte APP mRNA was gradually increased to reach a maximum at 3 days after activation with lectin mitogen PHA. However, the $A{\beta}$ immunoreactivity an cell surface remained constant during stimulation with PHA, indicating that the release of APP(secreted farm of APP) might be increased. A very large increase in soluble APP secretion was observed in T-lymphocyte upon activation, but only law levels in the resting stale. Immunoblot was carried out an the protein obtained from cell lysate after stimulating lymphocyte by applying PHA to the cultured lymphocyte, and the result was that $A{\beta}$ band of immature farm under 116 KDa marker decreased as the duration of culture was increased after PHA stimulation. The monoclonal $A{\beta}$ specific(4G8) and polyclonal APP antibodies did not inhibit the [$^3H$]-thymidine uptake of mitogen-treated lymphocytes significantly, suggesting that mitogenesis can not be inhibited by specific $A{\beta}$ and polyclonal APP antibody. These results suggest that APP is expressed in T-cell and might be closely associated with the function of T-cells.

• Korean Journal of Plant Resources
• /
• v.31 no.5
• /
• pp.433-452
• /
• 2018

This study was conducted to select candidates from plant resources for the purpose of improving or treating Alzheimer's disease, a type of dementia. One hundred and eighty-four plant extracts at a final concentration of $100{\mu}g/ml$ were screened to determine their capacity to inhibit acetylcholinesterase (AChE) by in vitro assay. From this AChE assay, seven plant extracts - including methanol ext. and water ext. of Phellaodendron amurense Rupr. (bark), methanol ext. of Nelumbo nucifera Gaertn (stamen/ovary), methanol ext. of Persicaria tinctoria H. GROSS (flower), methanol ext. of Coptis chinensis (rhizome), ethanol ext. of Cinnamomum cassia Blume(bark) and ethanol ext. of Carthamus tinctorius L. (fruit) - showed effective inhibition activity ranging from 18.7% to 63.1%. The selected extracts were testified their inhibition activities on AChE and BuChE (butyrylcholinesterase) at concentrations of 25, 50, 100, $200{\mu}g/ml$. In the AChE assay, five extracts including methanol ext. of Nelumbo nucifera Gaertn. (stamen/ovary), methanol ext. of Persicaria tinctoria H. GROSS (flower), methanol ext. of Coptis chinensis (rhizome), methanol ext. and water ext. of Phellaodendron amurense Rupr. (bark) showed inhibition activity of 15.0%~73.5%, 19.5%~63.5%, 81.6%~58.5%, 69.9%~80.5%, and 54.8%~78.3%, respectively, at concentrations of 25, 50, 100, $200{\mu}g/ml$. In the BuChE assay, the extracts of Nelumbo nucifera Gaertn. (stamen/ovary), Persicaria tinctoria H. GROSS (flower), and Coptis chinensis (rhizome) showed inhibitory capacities of 58.9~81.6%, 45.8%~72.4%, and 33.1%~55.4% at concentrations of 25, 50, 100, $200{\mu}g/ml$, respectively. In conclusion, it is suggested that Nelumbo nucifera Gaertn. (stamen/ovary), Persicaria tinctoria H. GROSS, Coptis chinensis (rhizome) and Phellaodendron amurense Rupr. (bark) could be selected as candidate materials for improving or treating Alzheimer's disease on the basis of further study.

• The Korean Journal of Nuclear Medicine
• /
• v.37 no.6
• /
• pp.374-381
• /
• 2003

Purpose: Determining an appropriate thresholding is crucial for PDG PET analysis since strong control of Type I error could fail to find pathological differences between eariy Alzheimer' disease (AD) patients and healthy normal controls. We compared the SPM results on FDG PET imaging of early AD using uncorrected p-value, random-field based corrected p-value and false discovery rate (FDR) control. Materials and Methods: Twenty-eight patients ($66{\pm}7$ years old) with early AD and 18 age-matched normal controls ($68{\pm}6$ years old) underwent FDG brain PET. To identify brain regions with hypo-metabolism in group or individual patient compared to normal controls, group images or each patient's image was compared with normal controls usingthe same fixed p-value of 0.001 on uncorrected thresholding, random-field based corrected thresholding and FDR control. Results: The number of hypo-metabolic voxels was smallest in corrected p-value method, largest in uncorrected p-value method and intermediate in FDG thresholding in group analysis. Three types of result pattern were found. The first was that corrected p-value did not yield any voxel positive but FDR gave a few significantly hypometabolic voxels (8/28, 29%). The second was that both corrected p-value and FDR did not yield any positive region but numerous positive voxels were found with the threshold of uncorrected p-values (6/28, 21%). The last was that FDR was detected as many positive voxels as uncorrected p-value method (14/28, 50%). Conclusions FDR control could identify hypo-metaboiic areas in group or individual patients with early AD. We recommend FDR control instead of uncorrected or random-field corrected thresholding method to find the areas showing hypometabolism especially in small group or individual analysis of FDG PET.

• Journal of Pharmaceutical Investigation
• /
• v.31 no.1
• /
• pp.49-55
• /
• 2001

Acetyl-L-carnitine (ALC), an endogenous component of the L-carnitine family, is naturally occurring molecule synthesized from L-carnitine (LC) by carnitine acetyl transferase. ALC has been shown to improve the cognitive performance of patients suffering from dementia of the Alzheimer's type and proposed for treating Alzheimer's disease in pharmacological doses. The purpose of the present study was to evaluate the bioequivalence of two ALC tablets, $Nicetile^{TM}$ (Dong-A pharmaceutical Co., Ltd.) and $Neurocetil^{TM}$ (Kyung-Dong Pharmaceutical Co., Ltd.), according to the guidelines of Korea Food and Drug Administration. Twenty six normal male volunteers, $22.80{\pm}2.76$ year in age and $63.07{\pm}7.98\;kg$ in body weight, were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After one tablet containing 500 mg of ALC was orally administered, blood was taken at predetermined time intervals and the concentrations of ALC in serum were determined using HPLC with fluorescence detector. Because of the presence of endogenous ALC, the calibration was performed using dialyzed serum. Pharmacokinetic parameters such as $AUC_t$, $C_{max}\;and\;T_{max}$ were calculated and ANOVA was utilized for the statistical analysis of the parameters. The results showed that the differences in $AUC_t$, $C_{max}\;and\;T_{max}$ between two tablets were 2.72%, -0.65% and -8.42%, respectively, when calculated against the $Nicetile^{TM}$ tablet. The powers $(1-{\beta})$ for $AUC_t\;and\;C_{max}$ were 94.87% and 87.17%, respectively. Minimum detectable differences $({\Delta})$ at ${\alpha}=0.05$ and $1-{\beta}=0.8$ were less than 20% (e.g., 15.58% and 19.16% $AUC_t\;C_{max}$, respectively). The 90% confidence intervals were within ${\pm}20%$ (e.g., $-11.84{\sim}6.41$ and $-10.57{\sim}11.88$for $AUC_t\;and\;C_{max}$, respectively). Two parameters met the criteria of KFDA for bioequivalence, indicating that $Neurocetil^{TM}$ tablet is bioequivalent to $Nicetile^{TM}$ tablet.

• Korean Journal of Clinical Pharmacy
• /
• v.11 no.2
• /
• pp.49-56
• /
• 2001

Acetyl-L-carnitine (ALC), an endogenous component of the L-carnitine family, is a naturally existing molecule synthesized from L-carnitine (LC) by carnitine acetyl transferase. ALC has been shown to improve the cognitive performance of patients suffering from dementia of the Alzheimer's type and proposed for treating Alzheimer's disease in pharmacological doses. The purpose of the present study was to evaluate the bioefuivalence of two ALC tablets, $Nicetile^{TM} (Dong-A Pharmaceutical Co.) and $L-Cartin^{TM}$ (Kuhn Il Pharmaceutical Co.), according to the guidelines of Korea Food and Drug Administration (KFDA). The ALC release from the two ALC tablets in vitro was tested using KP VII Apparatus II method in various dissolution media (pH 1.2, 6.0 and 6.8). Twenty six normal male volunteers, $24.46\pm3.67$ years in age and $64.45\pm5.54$ kg in body weight, were divided into two groups and a randomized $2\times2$cross-over study was employed. After one tablet containing 500 mg of ALC was orally administered, blood was taken at predetermined time intervals and the concentrations of ALC in serum were determined using HPLC with fluorescence detector. Because of the presence of endogenous ALC, the calibration was performed using dialyzed serum. The dissolution profiles of the two ALC tablets were similar in all the dissolution media. The pharmacokinetic parameters such as $AUC_t,\;C_{max}\;and\;T_{max}$ were calculated and ANOVA was utilized for the statistical analysis of the parameters. The results showed that the differences in $AUC_t,\;C_{max}\;and\;T_{max}$ between two tablets were $0.35\%,\;0.93\%\;and\;2.34\%$ respectively, when calculated against the $Nicetile^{TM} tablet. The powers $(1-\beta)\;for\;AUC_t$ , and Cmax were $98.72\%\;and\;85.48\%$, respectively. Minimum detectable differences $(\Delta)\;at\;\alpha=0.05\;and\;1-\beta=0.8$ were less than $20\%,\;(e.g.,\;13.21\%\;and\;18.42\%\;for\;AUC_t,\;and\;C_{max}$ respectively). The $90\%$ confidence intervals were within $\pm20\%\;(e.g.,\;-7.38\sim8.09\;and\;-9.86\sim11.72\;for\;AUC_t,\;and\;C_{max}$, respectively). These two parameters met the criteria of KFDA for bioequivalence, indicating that $L-Cartin^{TM}$ tablet is bioequivalent to $Nicetile^{TM} tablet.

• Archives of Pharmacal Research
• /
• v.27 no.6
• /
• pp.676-681
• /
• 2004

Acetyl-L-camitine (ALC), a naturally occurring endogenous compound, has been shown to improve the cognitive performance of patients with senile dementia Alzheimer＇s type, and to be involved in cholinergic neurotransmission. Because ALC is an endogenous compound, valida-tion of the analytical methods of ALC in the biological fluids is very important and difficult. This study was presented validation and correction for plasma ALC concentrations and pharmacok-inetics after oral administration of ALC to human volunteers. ALC concentrations in human plasma were corrected by subtracting the concentration of blank plasma from each sample. Precision and accuracy (bias %) for uncorrected ALC concentrations were below 2.6 and 6.5% for intra-days, and 4.0 and 9.4% for inter-days, respectively. Precision and accuracy (bias %)for corrected ALC concentrations were below 10.9 and 6.0% for intra-days, and 10.5 and 16.9% for inter-days, respectively. Quantitation limit was $0.1{\;}\mu\textrm{g}／mL$. After oral administration of a 500 mg ALC tablet to 8 healthy volunteers, the principle pharmacokinetic parameters were 4.2 h of the half-life$ (t_{1/2},{\beta})$, the area under the curve $(AUC_{0{\rightarrow}8){\;}of{\;}9.88{\;}\mu\textrm{g}{\cdot}h/mL$, and 3.1 h of the time ($T_{max}$) to reach $C_{max}$. This study first describes the pharmacokinetic study after oral admin-istration of a single dose of ALC in human volunteers.

• The Korean Journal of Nuclear Medicine
• /
• v.22 no.2
• /
• pp.147-156
• /
• 1988

알쯔하이머병 환자 11명, 우울증 환자 7명 그러고 정상 대조군 12명을 대상으로 $^{99m}Tc-HMPAO$ 뇌 SPECT를 이용하여 국소 뇌혈류 분포를 분석하여 다음과 같은 결과를 얻었다. 1) SPECT소견은 정상 대조군과 우울증군에서는 모두 정상이 있으나 알쯔하이머병군에서는 7명은 양측 측두엽 및 두정엽에, 3명은 편측 측두엽 및 두정엽에 그리고 1명은 전두엽에 뇌혈류 감소의 소견을 보였다. 2) 대뇌반구간 혈류분포의 변화를 비교하는 지수인 Cerebral asymmetry index는 정상 대조군에서 $0.08{\pm}0.03$, 알쯔하이머병군에서는 $0.11{\pm}0.04$ 그리고 우울증군에서는 $0.09{\pm}0.03$으로서 세 군간에 유의한 차이가 없었다. 3) 소뇌반구간 혈류분포의 변화를 비교하는 지수인 Percent index of cerebellar asymmetry는 정상 대조군에서 $0.4{\pm}0.7%$, 알쯔하이머병군에서 $-0.7{\pm}0.08%$ 그리고 우울증군에서 $-0.7{\pm}0.7%$로서 세군 간에 유의한 차이는 없었다. 4) 소뇌 계수치를 대조값으로 각 영역별 혈류분포의 변화정도를 비교하는 지수인 Region to cerebellum ratio는 우울증군에서는 정상 대조군과 유의한 차이를 보이지 않았으나 알쯔하이머병군에서는 양측 두정엽과 측두엽에서 유의한 감소를 보였다(p<0.05). 이상의 결과로 $^{99m}Tc-HMPAO$ 뇌 SPECT는 알쯔하이머병의 진단에 있어서 유용한 방법임을 알 수 있었다.