• BMB Reports
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• 제52권3호
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• pp.190-195
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• 2019

Acetaminophen (APAP) overdose can cause hepatotoxicity by inducing mitochondrial damage and subsequent necrosis in hepatocytes. Sirtuin2 (Sirt2) is an $NAD^+$-dependent deacetylase that regulates several biological processes, including hepatic gluconeogenesis, as well as inflammatory pathways. We show that APAP decreases the expression of Sirt2. Moreover, the ablation of Sirt2 attenuates APAP-induced liver injuries, such as oxidative stress and mitochondrial damage in hepatocytes. We found that Sirt2 deficiency alleviates the APAP-mediated endoplasmic reticulum (ER) stress and phosphorylation of the p70 ribosomal S6 kinase 1 (S6K1). Moreover, Sirt2 interacts with and deacetylates S6K1, followed by S6K1 phosphorylation induction. This study elucidates the molecular mechanisms underlying the protective role of Sirt2 inactivation in APAP-induced liver injuries.

• 한국의학물리학회:학술대회논문집
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• 한국의학물리학회 2002년도 Proceedings
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• pp.322-323
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• 2002

Partial volume averaging effect of PET data influences on the accuracy of quantitative measurements of regional brain metabolism because spatial resolution of PET is limited. The purpose of this study was to evaluate the accuracy of partial volume correction carried out on $^{18}$ F-PET images using Hoffman brain phantom. $^{18}$ F-PET Hoffman phantom images were co-registered to MR slices of the same phantom. All the MR slices of the phantom were then segmented to be binary images. Each of these binary images was convolved in 2 dimensions with the spatial resolution of the PET. The original PET images were then divided by the smoothed binary images in slice-by-slice, voxel-by-voxel basis resulting in larger PET image volume in size. This enlarged partial volume corrected PET image volume was multiplied by original binary image volume to exclude extracortical region. The evaluation of partial volume corrected PET image volume was performed by region of interests (ROI) analysis applying ROIs, which were drawn on cortical regions of the original MR image slices, to corrected and original PET image volume. From the ROI analysis, range of regional mean values increases of partial volume corrected PET images was 4 to 14%, and average increase for all the ROIs was about 10% in this phantom study. Hoffman brain phantom study was useful for the objective evaluation of the partial volume correction method. This MR-based correction method would be applicable to patients in the. quantitative analysis of FDG-PET studies.

• 대한간호학회지
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• 제34권7호
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• pp.1277-1287
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• 2004

Purpose: This study was to evaluate the effects of a short term comprehensive life style modification program on glycemic metabolism, lipid metabolism and body composition in type 2 diabetes mellitus patients. Method: A nonequivalent control group with a pre post test was designed. Data collection was done from October 2003 to June, 2004 at a hospital. Glycemic metabolism was measured by a.c., p.c. and $HbA_{1}c$, and lipid metabolism was measured by cholesterol, HDL cholesterol, LDL cholesterol and triglycerides. Body Composition was measured by body weight, body mass index, waist, measurement waist per hip ratio, body fat, muscle weight and abdominal fat tissue(intra abdominal distance). The Experimental group, which was composed of 29 participants, was educated based on a life style modification protocol at a weekly meeting for 12 weeks and carried out exercise, diet along individual parameters and self monitoring, while 24 participants in the control group received only diet education. Result: 1. The experimental group showed a significant lower a.c.(t=2.11, p=.04) and $HbA_{1}c$(t=2.65, p=.01) compared to those of the control group. 2. The experimental group showed a significant lower LDL than the results of the control group(t=2.42, p=.02). 3. The experimental group showed a significant lower weight(t=3.09, p=.00), BMI(t=3.01, p=.00), body fat(t=2.94, p=.01) and abdominal fat tissue(t=3.05, p=.01) than those of the control group. Conclusion: The results provided evidence for the effectiveness of a short term comprehensive life style modification program composed of exercise, diet, support, self efficacy elevation and self monitoring in type 2 diabetes mellitus.

• Journal of Chest Surgery
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• 제33권6호
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• pp.445-468
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• 2000

Background: Retrograde cerebral perfusion(RCP) is currently used for brain protection during aorta surgery, however, for the safety of it, various data published so far are insufficient. We performed RCP using pig and investiaged various parameters of cerebral metabolism and brain injury after RCP under deep hypothermia. Material and Method: We used two experimental groups: in group I(7 pigs, 20 kg), we performed RCP for 120 minutes and in group II (5 pigs, 20 kg), we did it for 90 minutes. Nasopharyngeal temperature, jugular venous oxygen saturation, electroencephalogram were continuously monitored, and we checked the parameters of cerebral metabolism, histological changes and serum levels of neuron-specific enolose(NSE) and lactic dehydrogenase(LDH). Central venous pressure during RCP was mainained in the range of 25 to 30 mmHg. Result: Perfusion flow rates(ml/min) during RCP were 130$\pm$57.7(30 minutes), 108.6$\pm$55.2(60 minutes), 107.1$\pm$58.8(90 minutes), 98.6$\pm$58.7(120 minutes) in group I and 72$\pm$11.0(30 minutes), 72$\pm$11.0(60 minutes), 74$\pm$11.4(90 minutes) in group II. The ratios of drain flow to perfusion flow were 0.18(30 minutes), 0.19(60 minutes), 0.17(90 minutes), 0.16(120 minutes) in group I and 0.21, 0.20, 0.17 in group II. Oxygen consumptions(ml/min) during RCP were 1.80$\pm$1.37(30 minutes), 1.72$\pm$1.23(60 minutes), 1.38$\pm$0.82(90 minutes), 1.18$\pm$0.67(120 minutes) in group I and 1.56$\pm$0.28(30 minutes), 1.25$\pm$0.28(60 minutes), 1.13$\pm$0.26(90 minutes). We could observe an decreasing tendency of oxygen consumption after 90 minutes of RCP in group I. Cerebrovascular resistance(dynes.sec.cm-5) during RCP in group I incrased from 71370.9$\pm$369145.5 to 83920.9$\pm$49949.0 after the time frame of 90 minutes(p<0.05). Lactate(mg/min) appeared after 30 minutes of RCP and the levels were 0.15$\pm$0.07(30 minutes), 0.18$\pm$0.10(60 minutes), 0.19$\pm$0.19(90 minutes), 0.18$\pm$0.10(120 minutes) in group I and 0.13$\pm$0.09(30 minutes), 0.19$\pm$0.03(60 minutes), 0.29$\pm$0.11(90 minutes) in group II. Glucose utilization, exudation of carbon dioxide, differences of cerebral tissue acidosis between perfusion blood and drain blood were maintained constantly during RCP. Oxygen saturation levels(%) in drain blood during RCP were 22.9$\pm$4.4(30 minutes), 19.2$\pm$4.5(60 minutes), 17.7$\pm$2.8(90 minutes), 14.9$\pm$2.8(120 minutes) in group I and 21.3$\pm$8.6(30 minutes), 20.8$\pm$17.6(60 minutes), 21.1$\pm$12.1(90 minutes) in group II. There were no significant changes in cerebral metabolic parameters between two groups. Differences in serum levels of NSE and LDH between perfusion blood and drain blood during RCP showed no statistical significance. Serum levels of NSE and LDH after resuming of cardipulmonary bypass decreased to the level before RCP. Brain water contents were 0.73$\pm$0.03 in group I and 0.69$\pm$0.06 in group II and were higher than those of the controls(p<0.05). The light microscopic findings of cerebral neocortex, basal ganglia, hippocampus(CA1 region) and cerebellum showed no evidence of cerebral injury in two groups and there were no different electron microscopy in both groups(neocortex, basal ganglia and hippocampus), but they were thought to be reversible findings. Conclusion: Although we did not proceed this study after survival of pigs, we could perform the RCP successfully for 120 minutes with minimal cerebral metabolism and no evidence of irreversible brain damage. The results of NSE and LDH during and after RCP should be reevaluated with survival data.

• Journal of Nutrition and Health
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• 제31권3호
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• pp.243-252
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• 1998

This study was conducted to investigated the short-term effects of early weaning and protein intake on organ and cell growth, nitrogen metabolism and physiological functions of rats. Five groups of early weaned rats separated from the dam on the 15th day postpartum were each given one five diets consisting of either one of the three levels of casein-low(8%), -normal (16%), and -high(32%), or a normal level (16%) of isolated soy protein(ISP) or egg yolk protein, for 7 days. The normal weaned rats were fed maternal breast milk for three weeks from birth. On the 22nd day postpartum , all the rats were sacrificed . The weight gain of the early weaned rats, especially the ones fed high protein, was observed to be significantly lower than that of the normal weaned rats. By the 15th day, of early weaning and especially in the ISP-fed rats, the total DNA contents of liver and kidney, which may be said to represent an index of cell numbers, significantly decreased, but their fresh and dry weight and protein/DNA ratio, allegedly representing an index of cell size, significantly increased , not affecting the cell number and cell size of brain. There were no differences in total serum protein and albumin concentrations between early and normal weaned rats. In the early weaned rats observed , the serum urea N and $\alpha$-amino N concentrations significantly increased in high protein-fed rats, and decreased in low protein-fed rats. Another observation was that no significant difference was noticed as regards to serum GOT activity, total bilirubin, uric acid, and creatinine concentration, which may represent indices of liver and kidney functions, among rat groups, GPT activity was an exception . These results suggest that premature weaning and the quality and quantity of dietary protein significantly affect organ and cell growth and nitrogen metabolism but does not seriously affect physiological functions in the neonatal development of rats.

• 대한의용생체공학회:의공학회지
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• 제32권1호
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• pp.55-60
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• 2011

Although sound intensity is considered as one of important factors in auditory processing, its neural mechanism in auditory neurons with limited dynamic range of firing rates is still unclear. In this study, we examined the effect of sound intensity adaptation on the change of glucose metabolism in a rat brain using [F-18] micro positron emission tomography (PET) neuroimaging technique. In the experiment, broadband white noise sound was given for 30 minutes after the [F-18]FDG injection in order to explore the functional adaptation of rat brain into the sound intensity levels. Nine rats were scanned with four different sound intensity levels: 40 dB, 60 dB, 80 dB, 100 dB sound pressure level (SPL) for four weeks. When glucose uptake during the adaptation of a high intensity sound level (100 dB SPL) was compared with that during adaptation to a low intensity level (40 dB SPL) in the experiment, the former induced a greater uptake at bilateral cochlear nucleus, superior olivary complexes and inferior colliculi in the auditory pathway. Expectedly, the metabolic activity in those areas linearly increased as the sound intensity level increased. In contrast, significant decrease interestingly occurred in the bilateral auditory cortices: The activities of auditory cortex proportionally decreased with higher sound intensities. It may reflect that the auditory cortex actively down-regulates neural activities when the sound gets louder.

• 한국의학물리학회지:의학물리
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• 제14권4호
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• pp.259-267
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• 2003

실험적 뇌손상 전후에 쥐의 뇌대사물질 변화를 4.7 T 자기공명분광법을 이용하여 조사하여 보았다. 자기공명 스펙트럼는 비교대상 그룹으로서 정상 쥐 우측 두전엽 피질에서 획득되었다. 유체타진손상기법(Fluid Percussion Injury)을 사용하여 뇌손상을 유발시킨후 3일 후 스펙트럼이 얻어졌다. 뇌손상 쥐의 뇌대사불질들의 변화는 정상쥐의 뇌대사물질들과 비교되었다. Neuronal marker로써 NAA/Cr 비율은 대조군에서 1.13$\pm$0.12이었고 뇌좌상부위에서 0.90$\pm$0.11로 손상전과 비교하여 대조군에 비해 유의성있는 감소소견을 나타내었으며 이는 neuronal loss를 의미하는 것으로 추정된다(P=0.001). Cho/Cr 비율은 대조군에서 0.76$\pm$0.15이었고 뇌좌상부위에서 0.91$\pm$0.17로 손상전과 비교하여 대조군에 비해 유의성있게 증가하는 경향을 나타내었으며 이는 생체막의 파괴나 염증반응과 관련된 것으로 추정된다(P=0.02). 하지만 Glx/Cr 비율은 손상전후에 유의성있는 변화를 나타내지 않았다. Lac/Cr 비율은 대조군에 비해 증가하는 경향을 나타내었고 이는 외상후 에너지 대사의 변위양상으로 고려되어진다. 이러한 소견들은 자기 공명분광법이 유체타진손상기법을 이용한 외상성 뇌좌상에서 신경병리학적 변화과정에 대한 이해를 증진시키고 나아가 외상에 의한 뇌좌상의 임상적인 평가를 위해 매우 유용한 modality임을 시사하는 것이라고 사료된다. 그러나 본 연구에서 몇몇의 케이스에서 voxel을 선정하면서 두개골의 일부가 포함되거나 혹은 죄상과 동반된 출혈로 인해 유용한 데이터를 획득하는데 어려움을 주기도 하였다. 앞으로 보다 더 세밀한 분석과 연구를 위해 유체타진 손상의 다양한 정도에서 대사물질들의 변화양상을 평가할 필요가 있을 것으로 사료된다. .

• 대한두개안면성형외과학회지
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• 제18권1호
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• pp.21-24
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• 2017

Background: In evaluation of craniosynostosis patients in terms of neurodevelopmental delay, positron emission tomography computed tomography (PET-CT) scan can be used to assess brain abnormalities through glucose metabolism. We aimed to determine the unnecessity of PET-CT in this study. Methods: Thirty-eight patients diagnosed with craniosynostosis who underwent distraction osteogenesis from October, 2010 to November, 2013 were reviewed. Magnetic resonance imaging (MRI) and PET-CT scan were carried out for evaluation of the brain structure and function, whereas X-ray and CT scan were taken for evaluation of the skull. Results: Nine patients reported abnormal MRI findings which were not significant, and five patients showed local problem on brain on PET-CT scan. No correlation was found among them. Conclusion: PET-CT evaluation of possible abnormal brain findings do not affect surgical planning or require additional therapy. Preoperative PET-CT scan is not the essential study to get any etiologic information of the disease consequences or to establish the treatment plan.

• 생물정신의학
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• 제5권1호
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• pp.66-70
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• 1998

Apoptosis is a form of cell death in which the cells shrink and exhibit nuclear chromatin condensation and DNA fragmentation, and yet maintain membrane integrity. Many lines of evidence have shown that brain neurons are vulnerable to degeneration by apoptosis. Also it has been suggested that apoptosis is one of the mechanism contributing neuronal loss in Alzheimer's disease(AD), since the conditions in the disease($A{\beta}$ peptide, oxidative stress, low energy metabolism) are the inducers that activate apoptosis. Indeed some neurons in vulnerable regions of the AD brain show DNA damage, chromatin condensation, and apoptic bodies. Consistently, mutations in AD causative genes(Amyloid precursor protein, Presenilin-1 and Presenilin- 2) increase $A{\beta}$ $peptide_{1-42}(A{\beta}_{1-42})$ and sensitize neuronal cell to apoposis. However, several lines of evidence have shown that the location of neuronal loss and $A{\beta}$ peptide deposition is not correlated in AD brain and transgenic mice brain over-expressing $A{\beta}_{1-42}$. Taken together, these data may indicated that $A{\beta}$ peptide(and other causative factors of AD) can interact with other cellular insults or risk factors to exacerbate pathological mechansim of AD through apoptosis. Thus, this review discusses possible role and mechanism of apoptosis in AD.

• Toxicological Research
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• 제34권3호
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• pp.267-279
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• 2018

Neurolathyrism is a neurodegenerative disorder characterized by spastic paraplegia resulting from the excessive consumption of Lathyrus sativus (Grass pea). ${\beta}$-N-Oxalyl-L-${\alpha},{\beta}$-diaminopropionic acid (L-ODAP) is the primary neurotoxic component in this pea. The present study attempted to evaluate the proteome-wide alterations in chick brain 2 hr and 4 hr post L-ODAP treatment. Proteomic analysis of chick brain homogenates revealed several proteins involved in cytoskeletal structure, signaling, cellular metabolism, free radical scavenging, oxidative stress and neurodegenerative disorders were initially up-regulated at 2 hr and later recovered to normal levels by 4 hr. Since L-ODAP mediated neurotoxicity is mainly by excitotoxicity and oxidative stress related dysfunctions, this study further evaluated the role of L-ODAP in apoptosis in vitro using human neuroblastoma cell line, IMR-32. The in vitro studies carried out at $200{\mu}M$ L-ODAP for 4 hr indicate minimal intracellular ROS generation and alteration of mitochondrial membrane potential though not leading to apoptotic cell death. L-ODAP at low concentrations can be explored as a stimulator of various reactive oxygen species (ROS) mediated cell signaling pathways not detrimental to cells. Insights from our study may provide a platform to explore the beneficial side of L-ODAP at lower concentrations. This study is of significance especially in view of the Government of India lifting the ban on cultivation of low toxin Lathyrus varieties and consumption of this lentil.