• Progress in Medical Physics
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• v.14 no.4
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• pp.259-267
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• 2003

In vivo $^1$H magnetic resonance spectroscopy (MRS) at 4.7 T was applied to investigate the cerebral metabolite changes of mice brain before and after experimental brain trauma. In vivo $^1$H MR spectra were acquired from a voxel covering right parietal cortex in normal brain, used as control subjects. After experimental brain trauma using the fluid percussion injury (FPI) method, $^1$H MR spectra were acquired from the same lesion three days after trauma. Metabolite ratios of the injured lesion were compared to those of controls. After trauma, N-acetylaspartate (NAA)/creatine (Cr) ratio, as a neuronal marker was decreased significantly versus controls, indicating neuronal loss. The ratio of NAA/Cr in traumatic brain contusion was 0.90$\pm$0.11, while that in normal control subjects was 1.13$\pm$0.12 (P=0.001). Choline (Cho)/Cr ratio had a tendency to rise in experimental brain contusion (P=0.02). Cho/Cr ratio after trauma was 0.91$\pm$0.17 while that before traumas was 0.76$\pm$0.15. Cho/Cr ratio was increased and this might indicate a inflammatory activity. However, no significant difference of [(glutamate＋glutamine) (Glx)]/Cr was established between experimental traumatic brain injury models and normal controls. Lactate (Lac)/Cr ratio was appeared as a sign of shifted posttraumatic energy metabolism and increased versus controls. These findings strongly suggest that in vivo $^1$H MRS may be a useful modality for clinical evaluation of traumatic contusion and could aid in better understanding the neuropathologic process of traumatic contusion induced by FPI. In the present study, in vivo $^1$H MRS was proved to be a useful non-invasive method for in vivo diagnosis and monitoring of posttraumatic metabolism in models of brain contusion.

• Archives of Craniofacial Surgery
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• v.18 no.1
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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.

• Korean Journal of Biological Psychiatry
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• v.5 no.1
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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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• v.34 no.3
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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.

• International Journal of Oral Biology
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• v.34 no.1
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• pp.29-36
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• 2009

Cyclosporin A (CsA) has been used clinically as an immunosuppressive drug to prevent organ transplant rejection and in basic research as a mitochondrial permeability blocker. It has been reported that CsA has a protective role in severed neurons and a neurotrophic effect in neuronal cells. However, the molecular mechanisms underlying the stimulation of neuronal cell proliferation by CsA have not yet been elucidated. In our current study, we investigated CsA responsive proteins in PC12 cells using a systematic proteomic approach. The viability of these cells following CsA treatment increased in a dose- and time-dependent manner. Proteins in the CsA-treated PC12 cells were profiled by two-dimensional gel electrophoresis (2-DE) and identified by matrix-assisted laser desorption ionization time-of flight (MALDI-TOF) and electrospray ionization quadupole time-of-flight mass spectrometries (EIQ-TOFMS). This differential expression analysis showed significant changes for 10 proteins (6 up-regulated and 4 down-regulated) upon CsA treatment that were related to cell proliferation, metabolism and the stress response. These proteomics data further our understanding of the proliferation mechanisms of PC12 cells exposed to CsA and demonstrate that our methodology has potential to further elucidate the mechanisms and pathways involved.

• Archives of Pharmacal Research
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• v.29 no.7
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• pp.566-569
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• 2006

This study examined whether or not acute stress is linked to increases in the neurosteroid levels, which is a well-known neurotransmitters associated with stress stimuli. The ginsenoside, Rb1, was tested in order to better understand its potential effects on altering the neurosteroid levels and ultimately attenuating stress. The optimal stressed condition was checked by measuring the 5a-dihydroprogesterone (DHP) and allopregnanolone (THP) levels in the brain after immobilization stress at various times. Based on this result, an acute stress model was set up to give 30 min of immobilization stress. The DHP and THP brain levels of the stressed mice were then investigated after administering Rb1 orally (10 mg/kg). These results were compared with the neurosteroid level in the stressed mice not given Rb1. Saline was administered orally to the nonstressed mice to check the placebo effect. Acute immobilization stress induced an increase in the THP and DHP concentration in the frontal cortex and cerebellum. When Rb1 was administered orally prior to immobilization stress, the THP level in the frontal cortex and cerebellum was significantly lower than that in the stressed animals not given Rb1. On the other hand, the DHP level was lower in the cerebellum only. This suggests that the metabolism of the brain neurosteroids is linked to psychological stress, and Rb1 attenuates the stressinduced increase in neurosteroids.

• The Korean Journal of Physiology and Pharmacology
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• v.19 no.4
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• pp.309-318
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• 2015

Alcohol consumption increases the risk of type 2 diabetes. However, its effects on prediabetes or early diabetes have not been studied. We investigated endoplasmic reticulum (ER) stress in the pancreas and liver resulting from chronic alcohol consumption in the prediabetes and early stages of diabetes. We separated Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a type-2 diabetic animal model, into two groups based on diabetic stage: prediabetes and early diabetes were defined as occurrence between the ages of 11 to 16 weeks and 17 to 22 weeks, respectively. The experimental group received an ethanol-containing liquid diet for 6 weeks. An intraperitoneal glucose tolerance test was conducted after 16 and 22 weeks for the prediabetic and early diabetes groups, respectively. There were no significant differences in body weight between the control and ethanol groups. Fasting and 120-min glucose levels were lower and higher, respectively, in the ethanol group than in the control group. In prediabetes rats, alcohol induced significant expression of ER stress markers in the pancreas; however, alcohol did not affect the liver. In early diabetes rats, alcohol significantly increased most ER stress-marker levels in both the pancreas and liver. These results indicate that chronic alcohol consumption increased the risk of diabetes in prediabetic and early diabetic OLETF rats; the pancreas was more susceptible to damage than was the liver in the early diabetic stages, and the adaptive and proapoptotic pathway of ER stress may play key roles in the development and progression of diabetes affected by chronic alcohol ingestion.

• Journal of Nutrition and Health
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• v.4 no.1
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• pp.21-28
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• 1971

1. The effects of chloroform to the tissue lactic dehydrogenase (LDH) activities and its isozymes and to the tissue glutamic dehydrogenase (GDH) activities and its isoaymes are studied using the experimental albino male adult rats in this paper. The tissues studies are liver, kidney, heart, and brain. Besides the control group, two experimental groups are studied providing succeedingly 4 days interpariental administrations of chloroform, 0.0025ml and 0.025ml per day respectively. The changes of body weights, weights of organs, activities of GDH and LDH and their isozymes of each tissues, are analysed. 2. The body weights of rats are decreased due to the chloroform administration. 3. There are no significant differences of weights of organs due to the chloroform administration. 4. The significant decreases of tissue GDH activities and the significant changes in percent distribution of the GDH isozymes are found due to the chloroform administration. This weight be interpretated that chloroform effects to the protein and amino acid metabolism of rats. 5. Due to the chloroform administration, the significant changes in tissue LDH activities and in percent distribution of tissue LDH isozymes indicating the decreases of $LDH_1$ which is the aerobic heart type and the increase of $LDH_5$ which is the anaerobic muscle type, are observed. This could be estimated that chloroform effects to the carbohydrate metabolism, particularly to the anaerobic glycolysis of rats.

• Korean Journal of Biological Psychiatry
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• v.15 no.3
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• pp.175-185
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• 2008

Accumulating evidence has suggested the existence of reciprocal communication between immune, endocrine, and neurotransmitter system. Cytokine hypothesis of depression implies that increased pro-inflammatory cytokine such as -1, IL-6, IL-12, TNF-${\alpha}$, and IFN-${\gamma}$ in major depression, acting neuromodulators, play a key role in the mediation of behavioral, neuroendocrine, and neurochemical disturbances in depression. Concerning the relation between cytokines and serotonin metabolism, pro-inflammatory cytokines have profound effects on the metabolism of brain serotonin through the enzyme indoleamine-2,3-dioxygenase(IDO) that metabolizes tryptophan, the precursor of 5-HT to neurodegenerative quinolinate and neuroprotective kynurenate. The neurodegeneration process is reinforced by the neurotoxic effect of the hypercortisolemia during depression. From this perspective, it is possible that efficacy of antidepressants in the treatment of depression may, at least in part, rely on downregulation of pro-inflammatory cytokine synthesis. So, the use of cytokine synthesis inhibitors or cytokine antagonists may be a new treatment approach in depression. However, at present the question whether cytokines play a causal role in the onset of depression or are mere epiphenomena sustaining depressive symptoms remains to be elucidated. Nevertheless, cytokine hypothesis has created new perspectives in the study of psychological and pathophysiological mechanism that are associated with major depression, as well as the prospect for developing a new generation antidepressants.

• The Korean Journal of Physiology and Pharmacology
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• v.4 no.6
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• pp.439-444
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• 2000

Tricyclic antidepressant clomipramine or selective serotonin reuptake inhibitors (SSRIs) have been commonly used for the treatment of premature ejaculation. In the present study, we analyzed the concentrations of serotonin and 5-hydroxyindoleacetic acid (5-HIAA) in the medial preoptic area (MPOA) of the hypothalamus by awakening animal microdialysis following administration of clomipramine and various SSRIs. We then compared the serotonin metabolism and clinical effects of clomipramine and SSRIs on premature ejaculation. Basal extracellular serotonin level in the MPOA was higher than other brain regions and it was significantly increased by clomipramine and the SSRIs. The rank order of the concentration of serotonin at the MPOA was clomipramine, sertraline, paroxetine and fluoxetine and the concentrations of 5-HIAA was vice versa. The changes in serotonin concentration at the MPOA appeared closely associated with the clinical effects of these drugs on premature ejaculation. These results suggest that the serotonergic neuronal activity in the MPOA may have an selective inhibitory influence on ejaculation, and the effects of clomipramine and SSRIs on erectile function are mainly mediated by MPOA of the hypothalamus.