• Neonatal Medicine
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• v.18 no.1
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• pp.59-69
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• 2011

Purpose: Current studies have demonstrated the neuroprotective effects of 6-cyano-7-nitroquinoxalin-2,3-dione (CNQX) in many animal models of brain injury, including hypoxic-ischemic (HI) encephlopathy, trauma and excitotoxicity, but limited data are available for those during the neonatal periods. Here we investigated whether CNQX can protect the developing rat brain from HI injury via mediation of nitric oxide synthase. Methods: In an in vivo model, left carotid artery ligation was done in 7-day-old Sprague-Dawley (SD) rat pups. The animals were divided into six groups; normoxia (N), hypoxia (H), hypoxia with sham-operation (HS), hypoxia with operation (HO), HO treated with vehicle (HV), and HO treated with CNQX at a dose of 10 mg/kg (HC). Hypoxia was made by exposure to a 2 hr period in the hypoxic chamber (92% $N_2$, 8% $O_2$). In an in vitro model, embryonic cortical neuronal cell culture of SD rats at 18-day gestation was done. The cultured cells were divided into three groups: normoxia (N), hypoxia (H), and hypoxia treated with CNQX (HC). The N group was prepared in 5% $CO_2$ incubators and the other groups were placed in 1% $O_2$) incubators (94% $N_2$, 5% $CO_2$) for 16 hr. Results: In the in vitvo and in vivo models, the expressions of iNOS and eNOS were reduced in the hypoxia group when compared to the normoxia group, whereas they were increased in the CNQX-treated group compared to the hypoxia group. In contrast, the expression of nNOS was showed reversely. Conclusion: CNQX has neuroprotective property over perinatal HI brain injury via mediation of nitric oxide synthase.

• Clinical and Experimental Pediatrics
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• v.52 no.5
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• pp.594-602
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• 2009

Purpose : Transforming growth factor (TGF)-${\beta}1$ reportedly increases neuronal survival by inhibiting the induction of inducible nitric oxide synthase (NOS) in astrocytes and protecting neurons after excitotoxic injury. However, the neuroprotective mechanism of $TGF-{\beta}1$ on hypoxic-ischemic (HI) brain injury in neonatal rats is not clear. The aim of this study was to determine whether $TGF-{\beta}1$ has neuroprotective effects via a NO-mediated mechanism and N-methyl-D-aspartate (NMDA) receptor modulation on perinatal HI brain injury. Methods : Cortical cells were cultured using 19-day-pregnant Sprague-Dawley (SD) rats treated with $TGF-{\beta}1$ (1, 5, or 10 ng/mL) and incubated in a 1% O2 incubator for hypoxia. Seven-day-old SD rat pups were subjected to left carotid occlusion followed by 2 h of hypoxic exposure (7.5% $O_2$). $TGF-{\beta}1$ (0.5 ng/kg) was administered intracerebrally to the rats 30 min before HI brain injury. The expressions of NOS and NMDA receptors were measured. Results : In the in vitro model, the expressions of endothelial NOS (eNOS) and neuronal NOS (nNOS) increased in the hypoxic group and decreased in the 1 ng/mL $TGF-{\beta}1-treated$ group. In the in vivo model, the expression of inducible NOS (iNOS) decreased in the hypoxia group and increased in the $TGF-{\beta}1$-treated group. The expressions of eNOS and nNOS were reversed compared with the expression of iNOS. The expressions of all NMDA receptor subunits decreased in hypoxia group and increased in the $TGF-{\beta}1$-treated group except NR2C. Conclusion : The administration of $TGF-{\beta}1$ could significantly protect against perinatal HI brain injury via some parts of the NO-mediated or excitotoxic mechanism.

• Clinical and Experimental Pediatrics
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• v.46 no.10
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• pp.989-995
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• 2003

Purpose : Dexamethasone is frequently administered to prevent or treat chronic lung disease in human neonates who are also prone to hypoxic-ischemic(HI) insults. Recently, meta-analysis of the follow-up studies reveals a significantly increased odd ratio for the occurrence of cerebral palsy or an abnormal neurologic outcome, and there is conflicting evidence regarding the impact of dexamethasone exposure on HI brain injury. This study was conducted to explore the effect of post-HI dexamethasone administration on neuronal injury in neonatal rats. Methods : HI was produced in seven-day-old rats by right carotid artery ligation followed by two hours of 8% oxygen exposure. At the end of HI, the animals were injected intraperitoneally either with dexamethasone(0.5 mg/kg) or saline. Neuronal injury was assessed seven days after the HI by the area of infarction, TUNEL reactivity, Bcl-2 and Bax expression in brain. Results : Post-insult dexamethasone administration resulted in reduction of weight gain and a higher mortality rate during seven days after HI. Dexamethasone treatment revealed no effect on the size of brain infarction induced by HI. Bax protein expression increased in dexamethasone treated brain but Bcl-2 protein expression and TUNEL reactivity revealed no significant differences between dexamethasone treated and non treated brain. Increased Bax protein expression suggest upregulation of the apoptosis by dexamethasone. Conclusion : The result suggests the adverse role of Post-HI administration of dexamethasone in neonatal HI.

• Clinical and Experimental Pediatrics
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• v.46 no.10
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• pp.966-971
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• 2003

Purpose : It is now well established that infection and inflammation play an important role in the pathogenesis of ischemic brain damage. The loss of neutrophils from systemic circulation is an associated finding in injury mediated by granulocyte. Periventricular leukomalacia(PVL) caused by ischemia is the principal form of brain injury in premature infants. This study was conducted to evaluate whether the low neutrophil count is associated with periventricular leukomalacia(PVL) in premature infants. Methods : Retrospective review of medical records was undertaken. Subjects were premature infants with a birth weight of less than 1,500 gm, admitted to the Neonatal Intensive Care Unit of Kyungpook University Hospital. A complete blood count of peripheral blood was done within the 1st hour of life. Neutropenia was defined as absolute neutrophil count < $1,500/mm^3$, PVL as increased periventricular echodensities followed by cyst formation on ultrasonography or corresponding signs on brain MRI. Results : Thirteen infants out of a total population of 37 revealed neutropenia. Respiratory distress syndrome and requirement for respiratory support were not different between infants with neutropenia( neutropenia group) and infants without neutropenia(control group). Intraventricular hemorrhage (IVH) and grade 3 and 4 IVH were more frequent in neutropenia group(P<0.05). There was no statistically significant increase of PVL in neutropenia group. The neutrophil count was $18,760.0{\pm}10,266.1/mm^3$, $7,272.0{\pm}7,435.0/mm^3$ infants with PVL and $11,131.7{\pm}3,386.5/mm^3$, $2,407.5{\pm}1,933.1/mm^3$ in infants without PVL, respectively. The frequency of mechanical ventilation and artificial surfactant therapy was higher in infants with PVL compared with infants without PVL, but statistical analysis was not performed due to small number of subjects. Conclusion : A low number of neutrophils in the systemic circulation was not associated with an increased risk of PVL in premature infants.

• 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.

• Clinical and Experimental Pediatrics
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• v.51 no.11
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• pp.1205-1210
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• 2008

Purpose : The development of the corpus callosum occupies the entire period of cerebral formation. The myelination pattern on magnetic resonance imaging (MRI) is very useful to evaluate neurologic development and to predict neurologic outcome in high risk infants. The thickness of the corpus callosum is believed to depend on the myelination process. It is possible to calculate the length and thickness of the corpus callosum on MRI. Thus, we can quantitatively evaluate the development of the corpus callosum. We investigated the clinical significance of measuring various portions of the corpus callosum in neonate with neurologic disorders such as hypoxic brain damage and seizure disorder. Methods : Forty-two neonates were evaluated by brain MRI. We measured the size of the genu, body, transitional zone, splenium, and length of the corpus callosum. Each measurement was divided by the total length of the corpus callosum to obtain its corrected size. The ratio of corpus callosal length and the anteroposterior diameter of the brain was also measured. Results : There was no statistical significance in the sample size of each part of the corpus callosum. However, the corrected size or the ratio of body of the corpus callosum correlated with periventricular leukomalacia and hypoxic ischemic encephalopathy. Conclusion : The abnormal size of the corpus callosum showed a good correlation with periventricular leukomalacia and hypoxic ischemic encephalopathy in neonates. We can predict clinical neurological problems by estimation of the corpus callosum in the neonatal period.

• Journal of Chest Surgery
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• v.30 no.12
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• pp.1159-1166
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• 1997

For Improvement of lung preservation, many tripes of preservation solution were developed and tested. The aim of this study was to compare the effect of the most frequently used extracellular type pieservation solution (Low Potassium Dextran, LPD) with a newly developed trehalose containing extracellular type preservation solution(ET-Kyoto, ETK) on postischemic lung function. Twelve New-Zealand white rabbit lungs were harvested and studied on an isolated, blood-perfused model of lung function after 4 hours of cold ischemia at $10^{\circ}C$ In group I (n=6), lungs were preserved with 100 mL/kg of LPD solution; in group II(n=6), lungs were preserved with 100 mL/kg of ETK solution. A few minutes before flushing with preservation solutions, 20$\mu\textrm{g}$ of PGEI were injected into main pulmonary artery. Functions of the preserved lung were compared with PO2, PA pressure, t acheal air pressure, and drylwet ratio. The pulmonary efferent blood oxygen tension at the end of the 60-minute reperfusion period was higher in group II compacted with group I(486.5 $\pm$ 80.3 mmHg versus $432.5\pm82.9$ mmHg at FiO2 1.0, p-value = NS). The mean pulmonary arterial pressure was similar in both $groups.(33.7\pm2.2$ mmHg versus $35.5\pm2.0$ mmHg, p-value : NS). The peak inspiratory airway pressure was significantly lower in group 11(8.010.6 mmHg versus 11.8 $\pm$ 1.4 mmHg, p-value=0.02) The water content of the lung was lower in group II $(70.2\pm6.9%$ versus 78.5 $\pm6.1%),$ but not significant. These data demonstrate that a newly-developed trehalose-containing ET-Kyoto solution yield equal or slightly superior lung function after reperfusion compared with LPD solution.

• Journal of Chest Surgery
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• v.36 no.8
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• pp.576-582
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• 2003

During the Off-Pump Coronary Arterial Bypass surgery (OPCAB), the manipulation of the heart can depress cardiac contractility and cause hemodynamic instability. In this study, hemodynamic parameters were measured during operation and the laboratory and clinical data were investigated to evaluate their effects on postoperative outcome. Material and Method: From March 2001 to August 2002, 50 consecutive patients who underwent OPCAB were included in this study. During the same period, total number of CABG was 71 The blood pressure, pulmonary artery pressure, mixed venous oxygen saturation, and cardiac index were measured before manipulation, after application of stabilizer, and at the end of anastomosis. Postoperatively, we measured the cardiac enzymes such as CK-MB, troponin 1 and checked the amount of inotropes required, chest tube drainage, the amount of transfusion, duration of ventilator support, and duration of ICU stay. Result: The number of mean distal anastomoses was 2.8$\pm$0.9 per patient. On elevation and stabilization of the heart, systolic blood pressure was depressed and pulmonary artery pressure was elevated significantly, but during each anastomosis no significant changes were detected. The peak level of cardiac markers was 29.2$\pm$46.7 for CK-MB, 0.69$\pm$0.86 for troponin 1 on postoperative day f. Among the intraoperative hemodynamic parameters, the ischemic change of EKG and bolus injection of inotropes significantly affected the posteroperative cardiac enzymes. But, no difference other than the level of cardiac enzymes between the two groups with or without the ischemic change of EKG and bolus injection of inotropes was noticed. Conclusion: The significant hemodynamic changes occurred when the heart was elevated and stabilized, however during anastomoses there were no significant changes. Serum cardiac enzymes rose significantly in the group that showed the ischemic charge of EKG or needed the bolus injection of inotropes for maintaining hemodynamic stability intraoperatively, but it did not affect the postoperative outcome. In conclusion, the ischemic change of EKG and the need for bolus injection of intropes during operation may be very indicative for probable ischemia.

• The Korean Journal of Nuclear Medicine
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• v.33 no.1
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• pp.40-48
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• 1999

Purpose: The sensitivity of ST-depression in the electrocardiogram during exercise is influenced by the level of efforts. However, unlike the prevalence of ST-depression on exercise ECG, the degree of exercise is reported to do not influence the diagnostic ability of myocardial perfusion scan. Furthermore, the relation between the prevalence of myocardial ischemia and effort is still controversial. We evaluated the effect of the degree of exercise on the ability of SPECT imaging to detect coronary artery stenosis. Materials and Methods: The patient population was comprised of 111 patients (73 men and 38 women, mean age 56 years) who underwent an exercise test in conjunction with Tc-99m MIBI and cardiac catheterization within 3 months apart each other. The degree of exercise was classified into four groups according to the percentage of maximal predicted heart rate. The sensitivity and specificity was compared between each group. Results: The overall diagnostic sensitivity was significantly higher with Tc-99m MIBI SPECT than exercise ECG. The specificity was not significantly different between two tests. Sensitivity and specificity of Tc-99m MIBI was not different between four groups. Sensitivity for individual coronary stenosis seemed to be lower in subjects who had premature termination of exercise due to early appearance of ST depression. Conclusion: These results suggest that the overall diagnostic sensitivity of Tc-99m MIBI myocardial perfusion SPECT is not significantly affected by the degree of exercise in stable patients undergoing symptom-limited treadmill exercise testing. Myocardial perfusion SPECT imaging should be added to routine exercise stress testing for the detection of coronary artery disease.

• Nuclear Medicine and Molecular Imaging
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• v.43 no.6
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• pp.519-525
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• 2009

Purpose: F-18 fluorodeoxyglucose (FDG) uptake of myocardium is influenced by various factors. Increased glycolysis, and subsequent increased F-18 FDG uptake has been reported in ischemic cardiomyopathy. However, clinical significance of incidentally found myocardial F-18 FDG uptake has not been clarified. We retrospectively reviewed the degree and pattern of myocardial uptake in patients without history of ischemic heart disease who underwent torso F-18 FDG PET/CT for evaluation of neoplastic disease. Materials and Methods: From January 2005 to June 2009, 77 patients who underwent F-18 FDG PET/CT and Tc-99m sestamibi stress/rest SPECT within 3 months were enrolled. Results: Of 77 patients, 55 (71.4%) showed increased F-18 FDG uptake in the myocardium. In this population, 40 showed uniform uptake pattern, while 15 showed focal uptake. In patients with uniform uptake, 17 showed decreased uptake in the septum without perfusion defect on myocardial SPECT. Remaining 23 patients showed uniform uptake, with 1 reversible perfusion defect and 1 fixed perfusion defect. In 15 patients with focal uptake, 9 showed increased F-18 FDG uptake in the base, and only 1 of them showed reversible perfusion defect on myocardial SPECT. In the remaining 6 focal uptake group, 4 had reversible perfusion defect in the corresponding wall, and 1 had apical hypertrophy. Conclusion: We demonstrated that septal defect pattern and basal uptake pattern in the myocardium may represent normal variants. Focal myocardial uptake other than normal variants on oncologic torso F-18 FDG PET/CT with routine fasting protocol may suggest ischemic heart disease, thus further evaluation is warranted.