• The Korean Journal of Physiology and Pharmacology
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• v.9 no.4
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• pp.231-238
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• 2005

Neuronal apoptotic events, which result in cell death, are occurred in hypoxic/ischemic conditions. Estradiol is a female sex hormone with steroid structure known to provide neuroprotection through multiple mechanisms in the central nervous system. This study was aimed to investigate the signal transduction pathway of $CoCl_2$-induced neuronal cell death and the inhibitory effects of estradiol. Administration of $CoCl_2$ decreased cell viability in both a dose- and time-dependent manner in PC12 cells. $CoCl_2$-induced cell death produced genomic DNA fragmentation and morphologic changes such as cell shrinkage and condensed nuclei. It was found that $CoCl_2$-treated cells increased the reactive oxygen species (ROS) as well as caspase-8, -9 and -3 activities. However, pretreatment with estradiol before exposure to $CoCl_2$ prevented the reduction in cell viability reduction and attenuated DNA fragmentation and morphologic changes caused by $CoCl_2$. Furthermore, the $CoCl_2$-induced increases of ROS levels and caspases activities were attenuated by estradiol. Gene expression analysis revealed that estradiol blocked the underexpression of the Bcl-2 and ameliorated the increase in the release of cytochrome c from mitochondria into cytoplasm and Fas-ligand (Fas-L) upregulated by $CoCl_2$. These results suggest that $CoCl_2$ induce apoptosis in PC12 cells through both mitochondria- and death receptor-mediated cell death pathway. Estradiol was found to have a neuroprotective effect against $CoCl_2$-induced apoptosis through the inhibition of ROS production and by modulating apoptotic effectors associated with the mitochondria- and death-dependent pathway in PC12 cells.

• Korean Journal of Acupuncture
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• v.40 no.3
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• pp.79-89
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• 2023

Objectives : The purpose of this study is to investigate various application methods of focused ultrasound and apply them to clinical use in Korean medicine. Methods : Search was performed using the search engines of electronic databases, including PubMed, ScienceDirect, Cumulative Index to Nursing and Allied Health Literature (CINAHL), ScienceON, Oriental Medicine Advanced Searching Integrated System (OASIS), China National Knowledge Infrastructure (CNKI), Wanfang Data, Japan Science Technology Information Aggregator, Electronic (J-STAGE) and Citation Information by NII (CiNii), from inception to July 2023 without language limitation. Inclusion criteria were clinical studies including randomized controlled trials (RCTs), and animal experimental studies related with focused ultrasound treatments for acupoints or meridian sinews. Results : Total 17 papers, 7 for RCT, 6 for in vivo animal studies, and other experimental studies, were finally selected. Indications used in studies were shoulder pain, back pain, chronic back pain, and degenerative knee arthritis. In experimental studies, studies on animal models of hypoxic ischemic brain damage and hyperlipidemia were also conducted. As for the acupoints, LR3, LI4, and ST36 were used in clinical studies and, in animal experimental studies, GV20, KI1, and ST36 were used. As for the dose, 4 studies below 3 W/cm² and 3 studies in the range of 0.625 to 5 W/cm² in clinical studies, and all studies did not exceed 5 W/cm². In animal experimental studies, 0.5 W/cm², 2 W/cm², 7.5 WW/cm², 15 W/cm², 10~20 W/cm² were used. In all three studies describing the penetration depth during irradiation, it was less than 1 cm. Conclusions : We suggest that focused ultrasound is an appropriate treatment tool for stimulating the acupoints to transfer heat energy. Future studies with rigorous and well-designed RCTs for various diseases will be required to ascertain the focused ultrasound stimulate acupoints or meridian sinews.

• Investigative Magnetic Resonance Imaging
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• v.6 no.1
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• pp.64-72
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• 2002

Purpose : To introduce and demonstrate the advantages of the new hybrid two-dimensional (2D) proton spectroscopic imaging (SI) over the single voxel spectroscopy (SVS) and conventional 2D SI in the clinical application of spectroscopy for pediatric cerebral disease. Materials and Methods : Eighty-one hybrid 2D proton spectroscopic imaging was performed in 79 children (36 normal infants and children, 10 with hypoxic-ischemic injury, 20 with toxic-metabolic encephalopathy, seven with brain tumor, three with meningoencephalitis, one with neurofibromatosis, one with Sturge-Weber syndrome and one with lissencephaly) ranging in age from the third day of life to 15 years. In adult volunteers (n=5), all three techniques including hybrid 2D proton SI, SVS using PRESS sequence, and conventional 2D proton SI were performed. Both hybrid 2D proton SI and SVS using PRESS sequence were performed in clinical cases (n=). All measurements were performed with a 1.5-T scanner using standard head quadrature coil. The 16$\times$16 phase encoding steps were set on variable field of view (FOV) depending on the size of the brain. The hybrid volume of interest inside FOV was set as $75{\times}75{\times}15{\;}\textrm{mm}^3$ or smaller to get rid of unwanted fat signal. Point-resolved spectroscopy (TR/TE=1,500 msec/135 or 270msec) was employed with standard chemical shift selective saturation (CHESSI pulses for water suppression. The acquisition time and spectral quality of hybrid 2D proton SI were compared with those of SVS and conventional 2D proton SI. Results : The hybrid 2D proton SI was successfully conducted upon all patients.

• Clinical and Experimental Pediatrics
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• v.46 no.8
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• pp.789-794
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• 2003

Purpose : We intended to evaluate the effect of hypoxia-ischemia on extracellular striatal monoamine metabolism in neonatal rat brains by in vivo microdialysis. Methods : The right common carotid arteries of five or six-day old rats were surgically ligated, and the probes for microdialysis were inserted into the right striatum with stereotaxic instrument. After stabilization for two hours, artificial cerebrospinal fluid was infused via the probe for microdialysis and samples were collected during hypoxia-ischemia and recovery periods at 20 minute intervals. The concentrations of DA(dopamine), DOPAC(3,4-di-hydroxyphenyl acetic acid), HVA(homovanillic acid), NE(norepinephrine), and 5-HIAA(5-hydroxy indole-acetic acid) were measured by HPLC(high performance liquid chromatography) and the changes were analysed. Results : The striatal levels of dopamine metabolites such as DOPAC and HVA, were significantly decreased during hypoxia-ischemia, and increased to their basal level during reoxygenation(P<0.05). Dopamine mostly increased during hypoxia but statistically not significant(P>0.05). DOPAC showed the most remarkable decrease($23.0{\pm}4.2%$, P<0.05), during hypoxia-ischemia and increase to the basal levels during reoxygenation($120.8{\pm}54.9%$, P<0.05), and HVA showed the same pattern of changes as those of DOPAC during hypoxia-ischemia($35.3{\pm}7.6%$ of basal level, P<0.05) and reoxygenation ($105.8{\pm}32.3%$). However, the level of NE did not show significant changes during hypoxia-ischemia and reoxygenation. The levels of 5-HIAA decreased($74.9{\pm}3.1%$) and increased($118.1{\pm}7.8%$) during hypoxia-ischemia and reoxygenation, respectively(P<0.005). Conclusion : Hypoxia-ischemia had a significant influence on the metabolism of striatal monoamine in neonatal rat brains. These findings suggest that monoamine, especially dopamine, and its metabolites could have a significant role in the pathogenesis of hypoxic-ischemic injury of neonatal rat brains.

• Clinical and Experimental Pediatrics
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• v.50 no.9
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• pp.882-890
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• 2007

Purpose : Preterm very low birth weight infant have high rate of adverse neurodevelopmental sequale. Recently, there have been lots of reports that human umbilical cord blood transplantation ameliorates functional deficits in animal models as hypoxic ischemic injury. This pilot study was undertaken to determine the clinical efficacy and safety of autologous umbilical cord blood cell transplantation for preventing neurodevelopmental sequale in perterm VLBW. Methods : Subjects were 26 preterm infants whose birth weight are less than 1,500 g and delivered under the intrauterine period 34 weeks. Autologous umbilical mononuclear cells (about $5.87{\times}10^7/kg$) were injected to neonate via the umbilical vein on the postnatal 24-48 hour. The therapeutic efficacy was assessed by numbers of nucleated RBC, urinary uric acid/creatinine ratio, concentration of neuron specific enolase (NSE), interleukin 6 (IL6), interleukin-$1{\beta}$ ($IL-1{\beta}$), and glial cell derived neurotrophic factor (GDNF) in serum and cerebrospinal fluid on day 1 and 7. Results : There were no significant differences in the numbers of the nucleated RBC, urinary uric acid/creatinine ratio, concentration of creatine kinase between the transplanted infants and controls. But the nucleated RBC is more likely to be rapidly discharged in the transplanted group. In the transplanted group, the concentrations of IL6, $IL-1{\beta}$, and GDNF were no significant difference between day 1 and 7, although GDNF seemed to be elevated. Serum NSE concentration was significantly elevated after transplantation, but not in CSF. Conclusion : It is suggested that autologous umbilical cord blood transplantation in preterm very low birth weight infant is safe to apply clinical practice. Long term follow up study should be needed to evaluate the potential therapeutic effect of umbilical cord blood transplantation for neuroprotection.

• Clinical and Experimental Pediatrics
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• v.49 no.11
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• pp.1158-1166
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• 2006

Purpose : The purpose of this study is to make a diagnostic classification and discuss a diagnostic strategy of floppy infants by investigating clinical, neurological, electrophysiological, and genetic analysis of infants admitted to intensive care units with the complaint of hypotonia. Methods : A retrospective study was performed from Jan. 1993 to Dec. 2005 in neonatal and pediatric intensive care units of Seoul National University Children's Hospital. Clinical features and all tests related to hypotonia were investigated. Results : There were 21 cases of floppy infants admitted to intensive care units. Final diagnosis was classified as centra (7 cases[33.3 percent]), peripheral (11 cases [52.4 percent]), and unspecified (3 cases [14.3 percent]). Among the central group, three patients were diagnosed as hypoxic ischemic encephalopathy, two patients as Prader-Willi syndrome, one patient as chromosomal disorder, and one patient as transient hypotonia. Among the peripheral group, four patients were diagnosed as myotubular myopathy, three patients as SMA type 1, two patients as congenital myotonic dystrophy, one patient as congenital muscular dystrophy, and one as unspecified motor-neuron disease. Motor power was above grade 3 on average, and deep tendon reflex was brisk in the central group. Among investigations, electromyography showed 66 percent sensitivity in the peripheral group, and muscle biopsy was all diagnostic in the peripheral group. Brain image was diagnostic in the central group, and Prader-Willi FISH or karyotyping was helpful in diagnosis in central group. Morbidity and mortality was more severe in the peripheral group Conclusion : Classification of diagnosis by clinical characteristics in this study, and application of investigations step by step, may provide an effective diagnostic strategy.

• Clinical and Experimental Pediatrics
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• v.45 no.8
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• pp.961-966
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• 2002

Purpose : We compared the underlying or associated diseases according to the frequency of platelet transfusions in neonates with thrombocytopenia to know the factors predicting which patients will require multiple platelet transfusions. We also compared mortality. Methods : A retrospective study was performed in 72 neonates who received the platelet transfusions in neonatal intensive care unit(NICU) between August 1996 and July 2001. Group I received one platelet transfusion and group II received two or more. We compared the frequency of underlying or assodiated diseases such as sepsis/disseminated intravascular coagulopathy(DIC), respiratory distress syndrome(RDS), intraventricular hemorrhage(IVH), patent ductus arteriosus (PDA), necrotizing enterocolitis(NEC), liver or renal disease, and mortality between two groups. Results : Of the 72 patients, 29(40.2%) received one and 43(59.7%) received two or more transfusions; 16(22.2%) received four or more. There were no statistically significant differences in gestational age, birth weight, sex, and maternal history between two groups. C-section rate was higher in group II(20.7% vs. 55.8%, P<0.05) and the incidence of PDA was higher in group I (55.2% vs. 30.2%, P<0.05). Otherwise, there were no statistically significant differences in the incidence of sepsis/DIC, RDS, IVH, RDS, CLD, NEC, liver or renal disease, pulmonary hemorrhage and hypoxic ischemic encephalopathy, and mortality between group I and group II. Conclusion : There was no significant difference in clinical morbidity and mortality according to the frequency of platelet transfusion in neonates with thrombocytopenia. Further study is needed to know the predicting factor for multiple platelet transfusions in neonates with thrombocytopenia.

• Clinical and Experimental Pediatrics
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• v.48 no.12
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• pp.1342-1347
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• 2005

Purpose : Among perinatal risk factors, neonatal seizures are one of the strongest independent discriminators of adverse outcome, representing high risks of mortality and neurologic morbidity. This study was undertaken to evaluate the neurologic outcome of neonatal status epilepticus according to underlying etiology, seizure pattern, onset time, and duration. Methods : We reviewed retrospectively 36 neonates(19 males, 17 females) with status epilepticus who were admitted to the neonatal intensive care unit, Inha Hospital between July, 1988 and June, 2003. They were evaluated with neurologic examination, laboratory data, EEG findings, and neuroimaging studies etc. Results : The mean gestational period of the patients was $37.0{\pm}3.6$ weeks and birth weight was $2.70{\pm}0.82$ kilogram. Fifty two point eight percent of the neonates were male and 66.7 percent were born at term. The most common cause of neonatal status epilepticus was hypoxic-ischemic encephalopathy. In preterm babies, intracranial hemorrhages showed an especially high frequency(P=0.034). Gestational age and birth weight did not show a correlation with neurologic complications. The incidence of neurological sequelae were significantly related to prolonged seizures lasting more than 1 hour(P=0.002). Neonates with seizures within the first 72 hours tended to be more frequent among those who developed adverse outcomes(P=0.016). Generalized tonic seizures had the worst prognosis, whereas those children who had subtle seizures had better outcomes than any other type(P<0.05). Generalized tonic seizures were primarily represented on EEG by abnormal background, whereas subtle seizure showed a significantly more normal EEG than any other seizures(P<0.05). Conclusion : Our results indicate that neonatal status epilepticus with early onsets, prolonged durations. And generalized tonic types can predict an increased risk for neurologic sequelae. So, those seizures must be perceived as medical emergencies and treated aggressively with antiepileptic drugs.