• Clinical and Experimental Pediatrics
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• v.50 no.7
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• pp.686-693
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• 2007

Purpose : Mycophenolic acid (MPA), the active metabolite of mycophenolate mofetil (MMF), is a potent inhibitor of inosine-monophosphate dehydrogenase (IMPDH), a new immunosuppressive drug used. It was reported that MPA protected neurons after excitotoxic injury, induced apoptosis in microglial cells. However, the effects of MPA on hypoxic-ischemic (HI) brain injury has not been yet evaluated. Therefore, we examined whether MPA could be neuroprotective in perinatal HI brain injury using Rice-Vannucci model (in vivo) and in rat brain cortical cell culture induced by hypoxia (in vitro). Methods : Cortical cells were cultured using a 18-day-pregnant Sprague-Dawley (SD) rats and incubated in 1% $O_2$ incubator for hypoxia. MPA ($10{\mu}g/mL$) before or after a HI insult was treated. Seven-day-old SD rat pups were subjected to left carotid occlusion followed by 2 hours of hypoxic exposure (8% $O_2$). MPA (10 mg/kg) before or after a HI insult were administrated intraperitoneally. Apoptosis was measured using western blot and real-time PCR for Bcl-2, Bax, caspase-3. Results : H&E stain revealed increased brain volume in the MPA-treated group in vivo animal model of neonatal HI brain injury. Western blot and real-time PCR showed the expression of caspase-3 and Bax/Bcl-2 were decreased in the MPA-treated group In in vitro and in vivo model of perinatal HI brain injury, Conclusion : These results may suggest that the administration of MPA before HI insult could significantly protect against perinatal HI brain injury via anti-apoptotic mechanisms, which offers the possibility of MPA application for the treatment of neonatal HI encephalopathy.

• The Korean Journal of Nuclear Medicine
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• v.33 no.1
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• pp.28-39
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• 1999

Purpose: We investigated the difference of glucose metabolism of medial and lateral temporal lobes of patients with temporal lobe epilepsy (TLE) utilizing quantitative comparison of regional metabolic activities using asymmetric index. Materials and Methods: We studied 19 pathologically proven mesial TLE and 25 lateral TLE patients. Lateral TLE patients were either normal on magnetic resonance imaging (cryptogenic: n=14) or had structural lesions (lesional: n= 11). Asymmetric index (ASI) was calculated as [(ipsilateral-contralateral)/(ipsilateral+contralateral)]${\times}200$. Results: ASI of medial and lateral lobes of mesial TLE was decreased ($-16.4{\pm}8.3$ and $-12.1{\pm}5.5$, respectively). In cryptogenic lateral TLE, ASI of lateral temporal lobe was decreased ($-11.8{\pm}4.7$), whereas that of medial temporal lobe was not decreased ($-4.6{\pm}6.3$). ASI of medial lobe of lesional lateral TLE was $-7.3{\pm}9.1$, which was significantly different from that of mesial TLE (p<0.05). Patients with lesional lateral TLE had evident metabolic defects or decrease (ASI: $-22{\pm}10.5$) in lateral temporal lobe. While we could not find the difference of metabolic activity in lateral temporal lobes between cryptogenic lateral TLE and mesial TLE patients, the difference of metabolic activity was significant in medial temporal lobes which was revealed by ASI quantitation. Conclusion: Asymmetric decrease of metabolic activity in both medial and lateral temporal lobes indicates medial temporal epilepsy. Symmetry of metabolic activity in medial temporal lobe combined with asymmetry of that in lateral temporal lobe may give hints that the epileptogenic zone is lateral.

• The Korean Journal of Nuclear Medicine
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• v.38 no.1
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• pp.41-51
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• 2004

PURPOSE: Tourette's disorder (TD), which is characterized by multiple waxing and waning motor tics and one or more vocal tics, is known to be associated with abnormalities in the dopaminergic system. To testify our hypothesis that risperidone would improve tic symptoms of TD patients through the change of the dopaminergic system, we measured the dopamine transporter (DAT) densities between drug-naive children with TD and normal children, and investigated the DAT density before and after treatment with risperidone in drug-naive children with TD, using iodine-123 labelled $N-(3-iodopropen-2-yl)-2{\beta}-carbomethoxy-3beta-(4-chlorophenyl)tropane$ ($[^{123}I]IPT$) single photon omission computed tomography (SPECT). MATERIALS and METHODS: $[^{123}I]IPT$ SPECT Imaging and Yale Global Tic Severity Scale-Korean version (YGTSS-K) for assessing the tic symptom severity were carried out before and after treatment with risperidone for 8 weeks in nine drug-naive children with TD. Eleven normal children also underwent SPECT imaging 2 hours after an intravenous administration of $[^{123}I]IPT$. RESULTS: Drug-naive children with TD had a significantly greater increase in the specific/nonspecific DAT binding ratio of both basal ganglia compared with the normal children. However, no significant difference in the specific/nonspecific DAT binding ratio of the basal ganglia before and after treatment with risperidone in children with TD was found, although tic symptoms were significantly improved with risperidone. CONCLUSION: These findings suggest that DAT densities are directly associated with the pathophysiology of TD, however, that the effect of risperidone on tic symptoms in children with TD is not attributed to the change of dopaminergic system.

• The Korean Journal of Nuclear Medicine
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• v.38 no.1
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• pp.30-40
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• 2004

Purpose: The aims of this study were to find brain regions in which gray matter volume was reduced and to show the capability of voxel-based morphometry (VBM) analysis for lateralizing epileptogenic zones in medial temporal lobe epilepsy (mTLE). The findings were compared with fluorodeoxyglucose positron omission tomography (FDG PET). Materials and Methods: MR T1-weighted images of 12 left mTLE and 11 right mTLE patients were compared with those of 37 normal controls. Images were transformed to standard MNI space and averaged in order to create study-specific brain template. Each image was normalized to this local template and brain tissues were segmented. Modulation VBM analysis was performed in order to observe gray matter volume change. Gray matter was smoothed with a Gaussian kernel. After these preprocessing, statistical analysis was peformed using statistical parametric mapping software (SPM99). FDG PET images were compared with those of 22 normal controls using SPM. Results: Gray matter volume was significantly reduced in the left amygdala and hippocampus in left mTLE. In addition, volume of cerebellum, anterior cingulate, and fusiform gyrus in both sides and left insula was reduced. In right mTLE, volume was reduced significantly in right hippocampus. In contrast, FDG uptake was decreased in broad areas of left or right temporal lobes in left TLE and right TLE, respectively. Conclusions: Gray matter loss was found in the ipsilateral hippocampus by modulation VBM analysis in medial temporal lobe epilepsy. This VBM analysis might be useful in lateralizing the epileptogenic zones in medial temporal lobe epilepsy, while SPM analysis of FDG PET disclosed hypometabolic epileptogenic zones.

• Journal of Life Science
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• v.22 no.8
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• pp.1057-1063
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• 2012

Epilepsy is the most prevalent chronic neurological disorder and can be controlled by antiepileptic drugs (AEDs) in up to 70% of patients. We performed an association study between adverse drug reactions and the genetic polymorphisms of CYP2C9, CYP2C19, ABCB1, and SCN1A. The clinical data of 83 epilepsy patients who had received AEDs containing carbamazepine (CBZ) were collected. We extracted genomic DNA from peripheral blood and then genotyped CYP2C9 ($CYP2C9^*2$, $CYP2C9^*3$), CYP2C19 ($CYP2C9^*2$, $CYP2C9^*3$), ABCB1 (C3435T), and SCN1A (IVS5N+5 G>A) using direct sequencing. The allele frequencies of $CYP2C9^*3$, $CYP2C9^*2$, $CYP2C9^*3$, ABCB1 (3435C>T), and SCN1A (IVS5N+5 G>A) were 0.93, 0.72, 0.91, 0.61, and 0.55, respectively. Statistically significant differences were indicated from the data obtained. Patients with SCN1A genotype CC or CT were compared with patients with SCN1A genotype TT while using more than 500mg of carbamazepine. We have associated functional polymorphisms with the dose used in regular clinical practice for Korean epilepsy patients who had received antiepileptic drugs (AEDs) containing carbamazepine. For AEDs, we found that one of the SCN1A genotypes is associated with a 500 mg dose. There was no association found with CNS ADR caused by AEDs.

• Journal of Life Science
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• v.24 no.12
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• pp.1276-1283
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• 2014

Cell adhesion molecules determine the cell-cell binding and the interactions between cells and extracellular signals. Cell-cell junctional complexes, which maintain the structural integrity of tissues, consist of more than 50 proteins including multi-PDZ domain protein 1 (MUPP1). MUPP1 contains 13 postsynaptic density-95/disks large/zonula occludens-1 (PDZ) domains and serves a scaffolding function for transmembrane proteins and cytoskeletal proteins or signaling proteins, but the mechanism how MUPP1 links and stabilizes the juxtamembrane proteins has not yet been elucidated. We used the yeast two-hybrid system to identify proteins that interact with PDZ domains of MUPP1. We found an interaction between MUPP1 and cell adhesion molecule 1 (Cadm1, also known as SynCAM1, Necl-2, or TSLC1). Cadm1 bound to the second PDZ domain of MUPP1. The carboxyl (C)-terminal end of Cadm1 has a type II PDZ-association motif (-Y-F-I) which was essential for the interaction with MUPP1 in the yeast two-hybrid assay. MUPP1 also bound to the C-terminal cytoplasmic tail region of other Cadm family members (Cadm2, Cadm3, and Cadm4). In addition, these protein-protein interactions were observed in the glutathione S-transferase (GST) pull-down assay and by co-immunoprecipitation. Anti-MUPP1 antibody co-immunoprecipitated Cadm1 and Cadm4 with MUPP1 from mouse brain extracts. These results suggest that MUPP1 could mediate interaction between Cadms and cytoskeletal proteins.

• Journal of Preventive Medicine and Public Health
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• v.25 no.1 s.37
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• pp.13-25
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• 1992

This study was conducted to investigate the mechanism of protective effect by sodium selenite in methylmercuric chloride neurotoxicity, increasing intracellular $Ca^{2+}$concentration of the neuron. Methylmercuric chloride of 3mg/kg of body weight was administered simultaneously with sodium selenite of 5mg/kg and pretreatment of sodium selenite via intraperitoneal injection to rats. Also, effect of methylmercuric chloride($25{\mu}M,\;50{\mu}M,\;100{\mu}M$) and sodium selenite($200{\mu}M$) on free intrasynaptosomal $Ca^{2+}$ concentration were studied using the fluorescent $Ca^{2+}$ indicator fura -2 in vitro. After the treatment, at 6, 24, and 48 hours later, mercury in the cerebral cortex, liver and kidney tissues, succlnic dehydrogenase activities, adenosin-5'-triphosphate concentration, acetylcholinesterase activities, and intracellular $Ca^{2+}$ concentration in the cerebral cortex were determined in vivo. Cerebral synaptosomes of rats were incubated with methylmercuric chloride and sodium selenite in Hepes buffer for 10 minutes and free intrasynaptosomal $Ca^{2+}$ concentration were measured with fura-2 in vitro. The results were summarized as follows ; 1. The combined administration of $CH_3HgCl$ and $Na_2SeO_3$ and pretreatment of $Na_2SeO_3$ according to time significantly more increased in the cerebral cortex and decreased in the liver, kidney mercury concentrations compared to the administration of $CH_3HgCl$ only. 2. The combined administration of $CH_3HgCl$ and $Na_2SeO_3$ and pretreatment of $Na_2SeO_3$ increased more succinic dehydrogenase and acetylcholinesterase activities compared to the administration of $CH_3HgCl$ only. Particularly pretreatment of $Na_2SeO_3$ significantly more compared to the administration of $CH_3HgCl$ only. The concentration of adenosine-5'-triphosphate in $Na_2SeO_3$ treatment groups revealed a favourable effect compared to the administration of $CH_3HgCl$ only. 3. Intracellular $Ca^{2+}$ concentration in administration of $CH_3HgCl$ only was increased significantly more than control group in all test hours but was increased significantly more at 48 hours only after treatment in combined administration of $CH_3HgCl$ and $Na_2SeO_3$ and pretreatment of $Na_2SeO_3$ according to time interval more decreased significantly intracellular $Ca^{2+}$ concentration compared to the administration of $CH_3HgCl$ only. 4. Free intrasynaptosomal $Ca^{2+}$ concentration in the combined administration of $CH_3HgCl$ and $Na_2SeO_3$ was decreased ($24%{\sim}40%$) significantly more than the administration of $CH_3HgCl$ only. From the above results, the specific dosage of $Na_2SeO_3$ decreased increment of intracellular $Ca^{2+}$ concentration induced by administration of $CH_3HgCl$. These findings suggest the protective mechanism of $Na_2SeO_3$ on the neurotoxicity of $CH_3HgCl$.

• Journal of Veterinary Clinics
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• v.32 no.2
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• pp.141-147
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• 2015

Based on the results of previous studies, endoscopic biopsy sample's quality has a major impact on its adequacy for histopathology, and that the nature of the biopsy forceps can influence the specimen quality. The present study compared the effects of three different types of endoscopic biopsy forceps and two different operators on sample quality and adequacy for histopathology in three healthy cats. Every biopsy was performed between the major papilla and caudal duodenal flexure, and each operator performed five biopsies with each type of forceps on each cat, for a total of 90 biopsies. One pathologist evaluated the quality and adequacy of the obtained samples. Biopsies performed with large-cup forceps provided heavier and longer samples than the standard round forceps. With the same size forceps, the presence of alligator teeth had no effect on sample quality or adequacy for histopathological examination and assessment. Based on the results of the present study, although the standard round forceps could be used to obtain adequate samples for histopathology, large-cup forceps such as the standard oval and alligator jaw type have the advantage of obtaining high quality endoscopic samples.

• Journal of the Korean Society of Radiology
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• v.1 no.1
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• pp.17-23
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• 2007

Background: Cerebrovascular diseases are known to show different patterns of incidence among regions and races. Therefore, it is very important to determine the incidence pattern of a specific area in order to diagnose, treat and prevent cerebrovascular diseases. The objective of the present study is to analyze quantitatively the incidence ratios of hemorrhagic and ischemic cerebrovascular diseases by season, by gender and by age. Methods: The subjects of this study were 1603 patients hospitalized for hemorrhagic or ischemic cerebrovascular diseases at the Department of Neurosurgery or the Department of Neurology of a University Hospital. Statistical analysis of data used Excel 2003 of Microsoft, and t-test was conducted using ORIGIN 6.0 of MICROCAL. Results: In the subjects, the incidence ratios of hemorrhagic and ischemic cerebrovascular diseases for four years, the period of this research, were 38.55% and 61.45%, respectively. The mean and standard deviation of age when hemorrhagic cerebrovascular diseases occurred were 58.20 and 12.60, respectively, and the percentages of subjects in their 40s, 50s, 60s and 70s were all around 20%. On the contrary, the mean and standard deviation of age when ischemic cerebrovascular diseases occurred were 65.01 and 13.59, respectively. The average age of patients with ischemic cerebrovascular diseases was older than that of patients with hemorrhagic brain diseases, and the percentages of those in their 60s, 70s and 80s were 15.53%, 37.06% and 27.72%, respectively. The season when hemorrhagic cerebrovascular diseases appeared most frequently was winter, which was followed by summer, spring and autumn. The season when hemorrhagic cerebrovascular diseases appeared most frequently was spring, which was followed by summer, winter and autumn. Conclusions: In this study, the incidence rates of hemorrhagic and ischemic cerebrovascular diseases were 38.55% and 61.45%, showing the rising percentage of ischemic cerebrovascular diseases. For making adequate prevention and disease control plans, it is considered necessary to make a long-term epidemiological investigation of cerebrovascular diseases.

• Nuclear Medicine and Molecular Imaging
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• v.40 no.3
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• pp.148-154
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• 2006

Purpose: Although radionuclide cisternography (RNC) is an useful study to detect cerebrospinal fluid (CSF) leakage in the patient with spontaneous intracranial hypotension (SIH), it sometimes fails to demonstrate the site of CSF leakage. The aim of the study is to improve the detection of leakage site of CSF and to reduce time for the study in RNC using modified protocol (m-RNC). Materials & methods : The study consists of 8 studies of 7 patients ($38{\pm}8$ years, M:F=2:5) with SIH, who underwent m-RNC following administration of 185-222 MBq of $^{99m}Tc$-DTPA into the lumbar subarachnoid space. Sequential images were obtained the whole spine with the head including urinary bladder at 10 minute, 30 minute, 1 hour, 2 hour, 4 hour and 6 hour. Radioactivity of extradural space and urinary bladder was evaluated. Results: Leakage site of CSF was identified in all 8 cases by m-RNC. Leakage site was cervicothoracic junction (CTJ, n=3), CTJ with C1-2 (n=2), CTJ with thoracic spine, thoracolumbar spine and lumbar spine (each n=1). All cases presented leakage sites within 1 hour and multiple sites, where CTJ was included in 6 cases. Only one case presented additional site in 6 hour image. Early radioactivity within the urinary bladder was noted in 6 cases, but that was fellowing after identification of the leakage site. Conclusion: Radionuclide cisternography is sensitive to detect the leakage site of CSF and is expected to improve the detection of CSF leakage site and reduce time for the study using modified protocol.