• 약학회지
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• 제51권4호
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• pp.264-269
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• 2007

Alzheimer’s disease (AD) is characterized pathologically by the presence of intracellular neurofibrillary tangles and deposition of ${\beta}-amyloid $ (A ${\beta}$) peptides, which are generated by processing of amyloid precursor protein (APP). It is urgent to develop effective therapies for the treatment of AD, since our society rapidly accelerate aging. A${\beta}$ peptides have been believed to be neurotoxic and now are also considered to have effects on the mechanism of memory formation. In this study, effects of radicicol on the metabolism of APP were analyzed. Radicicol inhibited the secretion of A${\beta}$ from the Neuro2a cell line (APPswe cell) expressing APPswe. Beta-site APP cleaving enzyme (BACE) fluorescence resonance energy transfer (FRET) assay revealed that it inhibited BACE activity in a dose dependently manner. Immunoblotting study showed that it inhibited intracellular heat shock protein (HSP)90 and it increased the secretion of HSP90 from the APPswe cells. We suggest that radicicol inhibits APP metabolism and Ap generation by the means of HSP90 inhibitory mechanism and partially BACE inhibitory mechanism. This is the first report that radicicol inhibits the secretion of A${\beta}$ peptides from neuroblastoma cells.

• The Korean Journal of Pain
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• 제21권3호
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• pp.173-178
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• 2008

Background: The intrathecal (IT) $GABA_A$ receptor antagonist, bicuculline (BIC), results in tactile allodynia (TA) through disinhibition in the spinal cord. Such disinhibition is considered to be an important mechanism for neuropathic pain. Agmatine, an endogenous polyamine, has a neuro-protective effect in the central nervous system. We investigated the analgesic effects and mechanisms of agmatine action on BIC-induced TA. Methods: Male Sprague-Dawley rats, weighting 250-300 g, were subjected to implantations of PE-10 into the lumbar subarachnoid space for IT drug injection. Five days after surgery, either $10{\mu}l$ of normal saline (NS) or agmatine ($30{\mu}g$ or $10{\mu}g$) in $10{\mu}l$ NS were injected 10 min prior to BIC ($10{\mu}g$) or NMDA ($5{\mu}g$). We assessed the degree of TA (graded 0: no response, 1: mild response, 2: moderate response, 3: strong response) every 5 min for 30 min. Areas under curves and degree of TA were expressed as mean ${\pm}$ SEM. Results were analyzed using one-way ANOVA followed by a Tukey test for multiple comparisons. P < 0.05 was considered significant. Results: IT BIC-induced strong TA reached its peak and plateaued between 10 to 15 min. IT NS-NMDA induced mild transient TA for up to 15 min. Preemptive IT AG attenuated IT BIC-induced TA dose dependently and preemptive IT AG10 completely abolished the IT NMDA-induced TA. Conclusions: Preemptive IT AG attenuated the IT BIC-induced TA through inhibitory actions on postsynaptic NMDA receptor activation. AG might be a viable therapeutic option in the treatment of neuropathic pain.

• Journal of Korean Neurosurgical Society
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• 제57권5호
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• pp.335-341
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• 2015

Objective : The main causes of spinal cord ischemia are a variety of vascular pathologies causing acute arterial occlusions. We investigated neuro-protective effects of kefir on spinal cord ischemia injury in rats. Methods : Rats were divided into three groups : 1) sham operated control rats; 2) spinal cord ischemia group fed on a standard diet without kefir pretreatment; and 3) spinal cord ischemia group fed on a standard diet plus kefir. Spinal cord ischemia was performed by the infrarenal aorta cross-clamping model. The spinal cord was removed after the procedure. The biochemical and histopathological changes were observed within the samples. Functional assessment was performed for neurological deficit scores. Results : The kefir group was compared with the ischemia group, a significant decrease in malondialdehyde levels was observed (p<0.05). Catalase and superoxide dismutase levels of the kefir group were significantly higher than ischemia group (p<0.05). In histopathological samples, the kefir group is compared with ischemia group, there was a significant decrease in numbers of dead and degenerated neurons (p<0.05). In immunohistochemical staining, hipoxia-inducible factor-$1{\alpha}$ and caspase 3 immunopositive neurons were significantly decreased in kefir group compared with ischemia group (p<0.05). The neurological deficit scores of kefir group were significantly higher than ischemia group at 24 h (p<0.05). Conclusion : Our study revealed that kefir pretreatment in spinal cord ischemia/reperfusion reduced oxidative stress and neuronal degeneration as a neuroprotective agent. Ultrastructural studies are required in order for kefir to be developed as a promising therapeutic agent to be utilized for human spinal cord ischemia in the future.

• 혜화의학회지
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• 제19권2호
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• pp.57-64
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• 2011

Parkinson's disease is a degenerative disease of a cranial nerve and has a main symptoms of irregular movement of muscle, stiffening, trembling which occurred by about 1% of population in the age of over 65. Moreover, the and prevalence rate and attack rate are soaring according to increase of elderly population. However, allopathy and surgery were done through dopamine and anticholinergic medicine for treatment but it developed a lot of complications due to medicine and progress since it makes slow progress or can't stop the treatment. Hereupon, I report that there is a case on one of the patients Young Jin Oriental Medical Clinic. The patient who is in state of treatment termination who doesn't need any further remedy and no worsening of symptoms after conduction of therapies of dialectic and 5 upright life cure regulations. 5 upright life cure regulations means five practive way for improvement of nature healing power. Upon undertaking the 5 upright life cure regulations, there were found significant results in such tests as Unified Parkinson Disease Rating Scale (UPDRS), Hoehn & Yahr Staging Scale, and Activity of Daily Living (ADL), and the ingestion of Benztropine 1mg and Requip 0.25mg was decreased from 3 times to 0 times. The study offers objective clinical data on Oriental Medicine treatment for Parkinson's disease which is one of representative neuro-degenerative diseases and thus broadens the application range of Oriental Medical treatment and presents the fundamental data on the clinical research on Parkinson's disease by adopting evidence-based medicine (EBM).

• Bulletin of the Korean Chemical Society
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• 제33권1호
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• pp.177-182
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• 2012

A new composition of standardized Scutellariae Radix extract (HPO12) was developed for treatment of Alzheimer's disease. For the preclinical pharmacokinetic study of HPO12, a rapid, sensitive, and selective LCMS/MS method was developed and validated for the simultaneous determination of 4 bioactive compounds, baicalein, baicalin, wogonin, and wogonoside. After extraction with ethylacetate, chromatographic analysis was performed on a Thermo $C_{18}$ column ($150mm{\times}2.1mm$, $3{\mu}m$) with a mobile phase consisting of 0.1% formic acid (A) and 0.1% formic acid in 95% acetonitrile (B) by using gradient elution at a flow rate of $250{\mu}L/min$. Analytes introduced to a mass spectrometer were monitored by multiple reaction monitoring (MRM) in positive ion mode. Using $25{\mu}L$ of plasma sample, the method was validated over the following concentration ranges: 25-5000 ng/mL for baicalein, 20-40000 ng/mL for baicalin, 1-1000 ng/mL for wogonin, and 5-10000 ng/mL for wogonoside. The intra- and inter-day precision and accuracy of the quality control samples at the 4 concentrations showed $\leq$ 13.7% relative standard deviation (RSD) and 86.6-105.5% accuracy. The method was successfully applied to determine the concentrations of baicalein, baicalin, wogonin, and wogonoside in rat plasma after intraperitoneal and oral administrations of HPO12.

• Journal of Korean Neurosurgical Society
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• 제49권5호
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• pp.262-266
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• 2011

Objective : The endocrine dysfunction after the operation for suprasellar arachnoid cysts is not rare. The careful operation to prevent structures can prevent this complication, but it is not enough and effective to prevent it. Authors present technical surgical considerations to prevent this complication with a review of our suprasellar arachnoid cyst patients who had postoperative endocrine dysfunction. Methods : From January 2002 to December 2009, eight patients who had suprasellar arachnoid cysts with visual impairment underwent surgery. The mean age was 57.1 years (range, 33-77). Preoperatively, their endocrine function was clinically normal, and laboratory hormonal levels were within normal ranges. Cyst fenestration was performed by craniotomy (n=6) or by a neuro-endoscopic procedure (n=2), and, simultaneously, along with a cyst wall biopsy. Results : The surgery was uneventful in all eight patients, and there were no neurological morbidities. However, in four patients, endocrine dysfunction occurred postoperatively. We compared these four patients (group A) to the other 4 patients without endocrine dysfunction (group B) with intraoperative findings and with the histopathological findings of the cyst wall biopsy. The group A patients had more abundant vasculature on the cystic wall than the group B patients according to both the intraoperative findings and the histopathological findings. Conclusion : When performing a surgical cyst wall fenestration, surgeons should try to minimize the destruction of the cystic wall vasculature and not to make the fenestration at a site that contains many vascular striae.

• 대한간호학회지
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• 제53권1호
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• pp.12-27
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• 2023

Purpose: This study aimed to develop a scale to measure distress in patients with ischemic stroke and verify its validity and reliability. Methods: Preliminary items were developed from literature review and in-depth interviews. The final preliminary scale was confirmed through a content validity test of eight experts and a preliminary survey of 10 stroke patients. The participants for psychometric testing were 305 stroke patients in the outpatient clinic. Validity and reliability analyses included item analysis, exploratory and confirmatory factor analysis, convergent validity, known-group validity, and internal consistency of the scale. Results: The final scale consisted of 17 items and 3 factors. The three distinct factors were 'self-deprecation, worry about future health, and withdrawal from society' and this structure was validated using a confirmatory factor analysis. Convergent validity was supported by comparison with the Center for Epidemiologic Studies Depression Scale (r = .54, p < .001) and Brief Illness Perception Questionnaire (r = .67, p < .001). Known-groups validity was verified by dividing groups according to 'duration since diagnosis' (t = 2.65, p = .009), 'presence of sequela' (t = 10.16, p < .001), and 'awareness of distress' (t = 12.09, p < .001). The internal consistency of the scale using Cronbach's α for the total items was .93. Conclusion: The Ischemic Stroke Distress Scale is a valid and reliable tool that reflects stroke distress effectively. It is expected to be used as a basic tool to develop various intervention strategies to reduce distress in ischemic stroke patients.

• Biomolecules & Therapeutics
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• 제28권3호
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• pp.259-266
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• 2020

The present research work primarily investigated whether spinosin has the potential of improving the pathogenesis of Alzheimer's disease (AD) driven by β-amyloid (Aβ) overproduction through impacting the procession of amyloid precursor protein (APP). Wild type mouse Neuro-2a cells (N2a/WT) and N2a stably expressing human APP695 (N2a/APP695) cells were treated with spinosin for 24 h. The levels of APP protein and secreted enzymes closely related to APP procession were examined by western blot analysis. Oxidative stress related proteins, such as nuclear factor-erythroid 2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1) were detected by immunofluorescence assay and western blot analysis, respectively. The intracellular reactive oxygen species (ROS) level was analyzed by flow cytometry, the levels of Aβ_1-42 were determined by ELISA kit, and Thioflavin T (ThT) assay was used to detect the effect of spinosin on Aβ_1-42 aggregation. The results showed that ROS induced the expression of ADAM10 and reduced the expression of BACE1, while spinosin inhibited ROS production by activating Nrf2 and up-regulating the expression of HO-1. Additionally, spinosin reduced Aβ_1-42 production by impacting the procession of APP. In addition, spinosin inhibited the aggregation of Aβ_1-42. In conclusion, spinosin reduced Aβ_1-42 production by activating the Nrf2/HO-1 pathway in N2a/WT and N2a/APP695 cells. Therefore, spinosin is expected to be a promising treatment of AD.

• Advances in biomechanics and applications
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• 제1권3호
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• pp.169-185
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• 2014

Computational multibody models of the elbow can provide a versatile tool to study joint mechanics, cartilage loading, ligament function and the effects of joint trauma and orthopaedic repair. An efficiently developed computational model can assist surgeons and other investigators in the design and evaluation of treatments for elbow injuries, and contribute to improvements in patient care. The purpose of this study was to develop an anatomically correct elbow joint model and validate the model against experimental data. The elbow model was constrained by multiple bundles of non-linear ligaments, three-dimensional deformable contacts between articulating geometries, and applied external loads. The developed anatomical computational models of the joint can then be incorporated into neuro-musculoskeletal models within a multibody framework. In the approach presented here, volume images of two cadaver elbows were generated by computed tomography (CT) and one elbow by magnetic resonance imaging (MRI) to construct the three-dimensional bone geometries for the model. The ligaments and triceps tendon were represented with non-linear spring-damper elements as a function of stiffness, ligament length and ligament zero-load length. Articular cartilage was represented as uniform thickness solids that allowed prediction of compliant contact forces. As a final step, the subject specific model was validated by comparing predicted kinematics and triceps tendon forces to experimentally obtained data of the identically loaded cadaver elbow. The maximum root mean square (RMS) error between the predicted and measured kinematics during the complete testing cycle was 4.9 mm medial-lateral translational of the radius relative to the humerus (for Specimen 2 in this study) and 5.30 internal-external rotation of the radius relative to the humerus (for Specimen 3 in this study). The maximum RMS error for triceps tendon force was 7.6 N (for Specimen 3).

• 전자공학회논문지SC
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• 제48권2호
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• pp.80-85
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• 2011

알츠하이머병(AD: Alzheimer's disease)과 파킨슨병(PD: Parkinson's disease)은 가장 흔한 퇴행성 뇌신경질환이다. 본 연구에서는 라만 스펙트럼을 이용하여 AD와 PD를 분류하기 위해 특징 추출하는 방법을 제안하였다. 혈소판으로부터 측정한 라만 스펙트럼에 먼저 smoothing을 적용한 다음 기준선의 왜곡을 제거하고 스펙트럼의 기준 피크를 중심으로 그 위치를 정렬하는 순서로 이루어진 전처리 과정을 적용하였다. 전처리 과정을 수행한 스펙트럼에서 AD와 PD를 구별할 수 있는 특징을 조사하였고 그 결과 743과 $757cm^{-1}$ 영역의 피크 비와 1248과 $1448cm^{-1}$ 영역의 피크 크기가 가장 변별력 있는 특징임을 확인하였다. 실험 결과에 따르면, 총 216개의 라만 스펙트럼에 대한 MAP(maximum a posteriori probability) 분류 실험에서 이 세 개의 특징만으로도 약 95.8%의 분류율을 보였다.