• Journal of Nutrition and Health
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• v.42 no.5
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• pp.423-433
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• 2009

Folate and vitamin $B_{12}$ are essential cofactors for homocysteine (Hcy) metabolism. Homocysteinemia has been related with cardiovascular and neurodegenerative disease. We examined the effect of folate and/or vitamin $B_{12}$ deficiency on biomarkers of one carbon metabolism in blood, liver and brain, and analyzed the correlation between vitamin biomarkers in mild and moderate homocysteinemia. In this study, Sprague-Dawley male rats (5 groups, n = 10) were fed folatesufficient diet (FS), folate-deficient diet (FD) with 0 or 3 g homocystine (FSH and FDH), and folate-/vitamin $B_{12}$-deficient diet with 3 g homocystine (FDHCD) for 8 weeks. The FDH diet induced mild homocysteinemia (plasma Hcy 17.41 ${\pm}$ 1.94 nmol/mL) and the FDHCD diet induced moderate homocysteinemia (plasma Hcy 44.13 ${\pm}$ 2.65 nmol/mL), respectively. Although liver and brain folate levels were significantly lower compared with those values of rats fed FS or FSH (p < 0.001, p < 0.01 respectively), there were no significant differences in folate levels in liver and brain among the rats fed FD, FDH and FDHCD diet. However, rats fed FDHCD showed higher plasma folate levels (126.5 ${\pm}$ 9.6 nmol/L) compared with rats fed FD and FDH (21.1 ${\pm}$ 1.4 nmol/L, 22.0 ${\pm}$ 2.2 nmol/L)(p < 0.001), which is the feature of "ethyl-folate trap"by vitamin $B_{12}$ deficiency. Plasma Hcy was correlated with hepatic folate (r = -0.641, p < 0.01) but not with plasma folate or brain folate in this experimental condition. However, as we eliminated FDHCD group during correlation test, plasma Hcy was correlated with plasma folate (r = -0.581, p < 0.01), hepatic folate (r = -0.684, p < 0.01) and brain folate (r = -0.321, p < 0.05). Hepatic S-adenosylmethionine (SAM) level was lower in rats fed FD, FDH and FDHCD than in rats fed FS and FSH (p < 0.001, p < 0.001 respectively) and hepatic S-adenosylhomocysteine (SAH) level was significantly higher in those groups. The SAH level in brain was also significantly increased in rats fed FDHCD (p < 0.05). However, brain SAM level was not affected by folate and/or vitamin $B_{12}$ deficiency. This result suggests that dietary folate- and vitamin B12-deficiency may inhibit methylation in brain by increasing SAH rather than decreasing SAM level, which may be closely associated with impaired cognitive function in nutritional homocysteinemia.

• The Korean Journal of Nuclear Medicine Technology
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• v.19 no.1
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• pp.62-66
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• 2015

Purpose Various database comparison methods(DCM) are used for analyzing functional neuro-imaging. It is possible to statistically evaluate decreased or increased metabolism of abnormal patient's brain by comparing with asymptomatic controls in DCM. And results of DCM are additionally used for easily explaining defect region. The aim of this study was to evaluate usefulness of statistical parametric mapping(SPM) and scenium. Materials and Methods Data of 15 patients($62.02{\pm}15.03year$) underwent $^{18}F-FDG$ brain PET/CT were collected and analyzed. Biograph TruePoint 40 with TrueV, (Siemens) was used as a PET/CT scanner. Scenium(version 4.0) in Syngo.via(version VA30A) and SPM99 were applied for statistical evaluation. Consistency between PET reading and result of DCM were evaluated by 5 nuclear medicine physicians through a questionnaire survey. SUV and SD changes were evaluated by changing iteration, gaussian filter and matrix size in scenium. And average required time for generating result of SPM99 and scenium was compared by 3 medical technologists. Results Consistency from the result of SPM99 and scenium showed 84% and 92.4% compare to PET reading. When iteration 4, FWHM 8 and matrix size 168, SUV and SD were decreased by 0.59%, 8.73%, 4.69%, 20.38% and 0.88%, 8.25% respectively compare to routine parameter(iteration 8, FWHM 2 and matrix size 336) of scenium. Average required time of SPM99 and Scenium took 282 seconds and 116 seconds to generate result. Conclusion Results of SPM99 and Scenium showed high consistency compare to PET reading. Various parameters can be controled by user when using SPM. However, normal database needs to be acquired. And it takes significant amount of time and effort for the first set up. On the other hand, Scenium provides normal database even though modifiable parameters are limited. Therefore, more informations could be provided for brain PET/CT if properly understanding and selecting each DCM.

• Journal of Life Science
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• v.31 no.12
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• pp.1066-1071
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• 2021

The aim of this study was to examine the metabolic adjustment of lactate dehydrogenase (EC 1.1.1.27, LDH) isozymes to a change in dissolved oxygen (DO) in bluegill (Lepomis macrochirus). After bluegills were adapted to a constant environment in an aquarium, the DO was changed to investigate the activity of LDH isozyme and the relative ratio of subunits A, B, and C for each tissue. When the DO was decreased from 18 ppm to 6 ppm, LDH in skeletal muscle, heart, and brain tissues recovered to the level of control activity within 12, 12, and 6 hr, respectively. LDH activity changed in accordance with a change in DO. The compensation was performed rapidly and is thought to be an important function of LDH in enabling bluegills to adapt to their environment. In bluegill heart, eye, and brain tissues, the relative ratio of subunit A increased and showed a tendency to recover similarly to the subunit ratio of control groups up to 12 hr. It is thought that the anaerobic metabolism using subunit A was increased in the initial stage when DO was changed. In addition, the results revealed that subunit C was more similar to subunit A than subunit B. In bluegills, subunits A and C of LDH seem to be evolutionarily similar. LDH isozymes, mainly containing subunits A and C, are likely responsible for the function of pyruvate reductase, which plays a role in making the bluegill adapt to a hypoxic environment through anaerobic metabolism.

• Development and Reproduction
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• v.12 no.2
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• pp.117-124
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• 2008

The efficient strategies to cope with unpredictable and/or harmful environmental changes have been developed by every organism in order to ensure its survival and continuity of it's own species. As a results, all living things on earth maintain dynamically internal stability via a process termed 'homeostasis' among physiological parameters despite of external environment changes. Stress is an emotional and physical response to threat homeostasis. Stress may have not only transient but rather permanent effect on the organism; recent evidence clearly show that prenatal stress could organize or imprint permanently physiological systems without any change in genetic codes, a process known as 'epigenetic programming'. In this review, a series of reproduction-associated events occurred in prenatally stressed male rats such as alteration in the structure of sexually dimorphic brain regions, modification of neurotransmitter metabolism, changes in reproductive endocrine status, and finally, disorders of sexual behavior will be introduced. The fetal brain is highly sensitive to prenatal programming and glucocorticoids in particular have powerful brain-programming properties. The chronic hyperactivation of fetal brain by maternal stress-induced glucocorticoid input will provide new program via increasing the neuroplasticities. This 'increased neuroplasticities' will be the basis for the 'increased phenotypic plasticities' rendering the organism's better adaptation to environmental challenges. In conclusion, organism who experienced 'harsh' environment in his fetal life seems to give up a certain portion of reproductive competence to make good chance of survival in his future life by epigenetic (re)programming.

• Journal of Acupuncture Research
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• v.18 no.3
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• pp.56-68
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• 2001

Objective : Functional brain mapping study on acupuncture stimulation using the [14C]2-deoxyglucose([14C]2-DG) autoradiography provides quantitative data and visualized pathway in central nervous system(CNS). We aimed to investigate the neural pathway and spatial distribution of metabolic activity elicited in CNS on electroacupuncture stimulation using [14C]2-DG autoradiography. Methods : The study were divided into three groups by stimulation times. 45-mins stimulation group according to Sokoloffs method, 5-mins stimulation group according to Duncun's method, and 15-mins stimulation group. ;A venous catheter was equipped into right jugular vein. The rats (Sprague-Dawley rats, 230-260g) were kept fastened loosely on a holding platform without anesthesia. Electroacupuncture stimulation (5 ms, 2 Hz, 1~3 mA) were applied on the left Zusanli (ST36) acupoint and [14C]2-DG ($25{\mu}Ci/rat$) injection was performed through the catheter. After sacrifice, the brain and the spinal cord were made to sections for film image. The film images were digitalized as the isotope concentration based upon comparison of optical densities with that of the standards and normalized by the optical density of corpus callosum. Results : 1. 15-mins stimulation group was most effective among 3 experiments. 2. On 15-mins stimulation group, medial geniculate nucleus, intetpeduncular nucleus intermedius, ventral periolivary nucleus, caudal periolivary nucleus, medial superior olive, lateral paragigantocellular nucleus, including hypothalamic arcuate nucleus were increased by more than 25% (at least, p<0.05) by electroacupuncture stimulation. 3. Especially, the metabolism in hypothalamic arcuate nucleus was increased by 90% (p<0.05). 4. The fact that arcuate nucleus of hypothalamus might play a role of interconnection area between ascending and descending pathway of acupuncture stimulation was demonstrated visually. Conclusions : Advanced study on electroacupuncture stimulation elicited significant increase of metabolic activity in various nuclei of hypothalamus will provide the important experimental basis in research of the relationship between electroacupuncture stimulation and internal visceral functions.

• The Korean Journal of Zoology
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• v.33 no.4
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• pp.461-467
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• 1990

To investigate the neurological effect of acrylamide, whole brain of Intoxicated mouse induced early hindlimbs ataxia was examined by using the methods of SDS-PAGE and two-dimensional electrophoresis. In the gel patterns by SDS-PAGE, when the patterns of each group were compared relatively, there were no remakable changes but in the patterns of 2D-PAGE, some protein alterations were observed. Especially, the spots containing 20 (14,500, 5.64) and 21 (19,900, 6.78) were disappeared, and the spots 9 (31,300, 5.82), 11 (31,300, 5.36) and 19 (16,400, 5.42) showed marked decrease relatively in the case of treatment group. Among these changed spots, the spot 20 (14,500, 5.64) showed higher quantity than that of control group but several spots containing the spots 11 (31,300, 5.36), and 19(16.400, 5.42) were identical or equal to those of control In quantity in the case of recovery group. It seems that acrylamide might already inhibit the brain protein synthesis mechanism at the time of onset of distal neuropathy by participation in the protein metabolism so as to impair the brain regulation ability followed by a malfunction of mouse central nervous system (CNS) and recovery is gradually progressed with the dose and duration dependence after the cessation of acrylamide administration.

• The Korean Journal of Physiology
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• v.4 no.2
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• pp.25-31
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• 1970

Tissue homogenates of Ehrlich ascites tumor tissues and several normal tissue of mice were incubated separately in medium maintaining $C^{14}$_acetate concentrations of 5, 10, 20, 30, 40, 50 and 60 mg%, in order to determine maximum oxidative rates of acetate. In every incubation experiments, respiratory $CO_2$ samples rapped by alkaline which was placed in the center well of the incubation blask were analyzed for total $CO_2$ Production rates and their radoactivies. The fractions of $CO_2$ from medium acetate to total $CO_2$ production rate were obtained with relative specific activities (RSA) which were calculated by ratio between specific activities (SA) of $CO_2$ and medium $CO^{14}$_acetate and $CO_2$ production rates from medium acetate were calculated from RSA and total $CO_2$ production rates. Maximum plateau values of oxidative rates described above were determined at incubation experiments of various concentrations of medium acetate and compared the oxidative rates of acetate of tumor with those of normal tissues such as kidney, brain and liver. Maximum plateau values of total $CO_{2}$ Production rates were obtained at acetate concentration of 20 mg% and represent $25.0{\pm}0.54\;{\mu}M/hr/gm$ in the brain, $16.3{\pm}2.5$ in the kidney, $9.1{\pm}1.78$ in the liver and $11.5{\pm}3.2\;{\mu}M/hr/gm$ in the ascites tuners. Substancial $CO_2$ yield was observed in the tumor tissues as in the normal tissues. On the other hand, plateau values of RSA were $25.7{\pm}1.04%$ in thee brain, $9.1{\pm}0.72%$ in the kidney, $2.5{\pm}0.73%$ in the liver and $0.51{\pm}0.12%$ in the tumor tissues. $CO_2$ yields from the medium acetate, were 4.19 in the kidney, 2.28 in the brain, 0.228 in the liter and $0.059\;{\mu}M/hr/gm$ in the tumor tissue. These show wide range even in the normal tissue but remarkable decrease in the tumor tissue. This fact means that further oxidation of acetate was inhibited remarkably in the tumor tissue.

• The Journal of Korean Medicine
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• v.27 no.3 s.67
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• pp.107-131
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• 2006

Background and Aims: Dansamtongmek-tang (DSTMT) and Dansamsengmek-san (DSSMS) have been used for many years as therapeutic agents for the acute stage of cerebrovascular disease, hypertension and hyperlipidemia in Oriental medicine, but the effects of DSTMT and DSSMS on hyperlipidemia and safety for cell damage are not yet well-known. This study was done to investigate the effects of DSTMT and DSSMS on hyperlipidemia. Methods: In vivo test: after administering DSTMT and DSSMS to SHR and ICR occurred hyperlipidemia for 3 weeks, we analyzed body weight, cholesterol levels. TG, HDL-chol, LDL-chol, LDH in plasma, brain, liver and kidney tissue, and DNA by RT-PCR. In vitro test: after administering DSTMT and DSSMS to human hepatocellular carcinoma in hypoxia, we observed cell cohesion by light microscope, analyzed the inflow of Ca2+ by confocal laser scanning microscope and DNA by RT-PCR. Results: DSTMT significantly decreased the levels of triglyceride and increased the levels of HDL-cholesterol in SHR, and significantly decreased the levels of LDL-cholesterol and body weight and increased the levels of HDL-cholesterol in ICR. DSSMS significantly decreased body weight, total cholesterol levels, LDL-cholesterol, LDH and cardiac risk factor (CRE) in SHR and significantly decreased the levels of total cholesterol, triglyceride, LDL-cholesterol, LDH and CRF in ICR. DSTMT had an effect on protecting cells from damage by inhibiting production of p53 mRNA, and in DSSMS, by inhibiting production of p53 mRNA and p21 mRNA after hypoxia. DSTMT effectively blocked off Ca2+ at low density, but DSSMS effectively blocked off Ca2+ at high density. Both DSTMT and DSSMS had an effect on inhibiting lipid metabolism by blocking off production of apo B mRNA. Conclusions: These results suggest that DSTMT and DSSMS might be usefully applied for treatment of hyperlipidemia and suppression of brain damage.

• Clinical and Experimental Pediatrics
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• v.60 no.12
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• pp.403-407
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• 2017

Purpose: Quadriplegic children with cerebral palsy are more susceptible to osteoporosis because of various risk factors that interfere with bone metabolism. Pamidronate is effective for pediatric osteoporosis, but there are no guidelines for optimal dosage or duration of treatment in quadriplegic children with osteoporosis. We aimed to evaluate the efficacy of low-dose pamidronate treatment in these patients. Methods: Ten quadriplegic patients on antiepileptic drugs (6 male, 4 female patients; mean age, $10.9{\pm}5.76years$), with osteoporosis and gross motor function classification system level V, were treated with pamidronate (0.5-1.0 mg/kg/day, 2 consecutive days) every 3-4 months in a single institution. The patients received oral supplements of calcium and vitamin D before and during treatment. The lumbar spine bone mineral density (BMD) z score and biochemical markers of bone metabolism were measured regularly during treatment. Results: The main underlying disorder was perinatal hypoxic brain damage (40%, 4 of 10). The mean cumulative dose of pamidronate was $4.49{\pm}2.22mg/kg/yr$, and the mean treatment period was $10.8{\pm}3.32months$. The BMD z score of the lumbar spine showed a significant increase from $-4.22{\pm}1.24$ before treatment to $-2.61{\pm}1.69$ during treatment (P=0.008). Alkaline phosphatase decreased during treatment (P=0.037). Significant adverse drug reactions and new fractures were not reported. Conclusion: Low-dose pamidronate treatment for quadriplegic children with cerebral palsy increased lumbar BMD and reduced the incidence of fracture.

• Molecules and Cells
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• v.37 no.2
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• pp.161-171
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• 2014

In several lysosomal storage disorders, including Niemann-Pick disease Type C (NP-C), sphingolipids, including glycosphingolipids, particularly gangliosides, are the predominant storage materials in the brain, raising the possibility that accumulation of these lipids may be involved in the NP-C neurodegenerative process. However, correlation of these accumulations and NP-C neuropathology has not been fully characterized. Here we derived NP-C mice with complete and partial deletion of the Siat9 (encoding GM3 synthase) gene in order to investigate the role of ganglioside in NP-C pathogenesis. According to our results, NP-C mice with homozygotic deletion of GM3 synthase exhibited an enhanced neuropathological phenotype and died significantly earlier than NP-C mice. Notably, in contrast to complete depletion, NP-C mice with partial deletion of the GM3 synthase gene showed ameliorated NP-C neuropathology, including motor disability, demyelination, and abnormal accumulation of cholesterol and sphingolipids. These findings indicate the crucial role of GM3 synthesis in the NP-C phenotype and progression of CNS pathologic abnormality, suggesting that well-controlled inhibition of GM3 synthesis could be used as a therapeutic strategy.