• Proceedings of the Korean Environmental Health Society Conference
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• 2005.12a
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• pp.87-94
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• 2005

Results from previous studies revealed that metal level in the body is related to certain types of diseases. For example. serum copper level with chronic heart failure, iron and transferrin in the blood serum with acute cerebral vascular diseases, Zn in the CNS, lead with neurotoxicity, hypertension, genetic damage, arsenic with cancer skin lesion, Al with neurobehavioral function (cognitive impairment and memory disorder), and etc. The rate of stroke has increased in recent years and several metals were found to be responsible for causing stroke. This study compared several blood metal concentrations between stroke and non-stroke patients. Patients with stroke (116 samples) and non-stroke (111 samples including lowback pain and others) participated in this study. Total of 227 blood samples were collected and participants completed questionnaires regarding age, gender, occupation, residence, alcohol, smoking, and etc. To be qualified into the stroke group, patients have never experienced stroke previously. Subjects only included ischemic stroke and intracerebral hemorrhage patients diagnosed by brain CT and brain MRI. Patients with high risk of metal exposure such as herbal intake and job related exposure were excluded. 10ml of blood samples were analyzed by ICP-MS method at the Center of Nature and Science at Sangji University. Metal geometric mean (SD) concentrations in blood of study subjects showed higher values, 2.64-36.12%, than WHO reference values in Mn, Ni, Hg, Se, and As. Metal concentration in blood of stroke patients non-adjusted for potential confounders was higher except for Hg and also higher except for Ni in adjusted for potential confounders. Co was significantly higher in stroke patients (p=0.002) than non-stroke patients adjusted for potential confounders. Regression coefficient values of stroke patients was 0.17-8.25 in each metals. Odd ratio of stroke patients had 0.96 (Ni)-2.68 (Co) compared to non-stroke cases. This result means that Co increase of 1 raises the risk ratio of stroke by 2.86 times. Based on the results, metal concentration in blood seems to affect incidence of stroke.

• Journal of Chest Surgery
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• v.30 no.9
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• pp.876-884
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• 1997

Fourteen patients underwent orthotopic heart transplantation between March 1994 and May 1996 in Seoul National University Hospital. There were 9 male and 5 female patients, and the mean age was 40.8 $\pm$ 12.4 years ranged from 12 to 56 years. All patient were in NYHA Fc III or IV preoperatively. The underlying heart diseases were dilated cardiomyopathy in 11 and restrictive cardiomyopathy in 3. The mean age of donors was 24.9$\pm$ 10.2 years and the causes of the brain death were head trauma by traffic accidents in 8, subarachnoid hemorrhage in 2, 1 asphyxia, 1 fall down injury, 1 brain tumo , and 1 drowning, respectively The blood type was identical in 11, compatible in 2, and incompatible in 1 patient. The direct bicaval anastomosis technique was used in 11 cases, and standard right atrial anastomosis was done in the remaining 3 cases. The graft ischemic time was 158$\pm$44 minutes ranged 94 to 220 minutes. There were two hospital deaths(14.3%). The causes of deaths were 1 right ventricular failure followed by suspected cyclosporine induced hemolytic uremic syndrome and rejection, and 1 delayed massive bleeding, probably from rupture of the anastomotic pseudoaneurysm, respectively. The follow-up duration was 16$\pm$9 months(3 to 28 months). There was one late death(8.3%). All the other patients were in NYHA Fc I except one patient who was in hospital because of the acute rejection. The actuarial survival rates including hospital deaths were 93.7% at 1 month, 86.9% at 6 months, and 77$\pm$12% at 2 years. Conclusively, heart transplantation is the good strategy for the management of end stage heart disease with acceptable operative mortality and early follow-up results.

• Journal of Chest Surgery
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• v.31 no.10
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• pp.945-951
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• 1998

Background: Although profound hypothermia with total circulatory arrest(TCA) is a valuable maneuver in cardiac surgery, its applications have been limited due to serious complications, especially cerebral damage. In this study, the possible role of creatinine kinase-BB(CK-BB), an index enzyme of ischemic cerebral damage, was assayed as a parameter for the assessment of the cerebral complications after TCA. Hemoglobin(Hb), ionized calcium(Ca++), and blood glucose levels were also assessed as clinical parameters involved in cerebral damage. Materials and methods: Among patients with congenital heart disease, 18 patients who had been operated on with TCA were randomly selected and divided into two groups: 6 with acyanotic and 12 with cyanotic heart disease. Arterial blood from each patient was collected before and after TCA at scheduled times(15 min., 30 min, 1, 2, 4, 8, and 12hr). The levels of CK-BB, Hb, Ca++, and blood glucose were assessed in each sample. Results: As a whole, correlation between CK-BB level and blood sampling time after TCA was not statistically significant. Also, the difference in the level of CK-BB after TCA was not significant between the acyanotic and cyanotic groups. The levels of Hb and CK-BB correlated significantly. Conclusions: The results, which showed no correlation between the alterations in CK-BB level and the TCA duration, suggest that the single assay of the CK-BB level is not a representative measurement for the assessment of cerebral damage after TCA. Also, the cyanotic congenital heart disease group is not more vulnerable to cerebral damage induced by TCA.

• Biomolecules & Therapeutics
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• v.15 no.1
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• pp.16-26
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• 2007

Tissue plasminogen activator (tPA) is a serine protease catalyzing the proteolytic conversion of plasminogen into plasmin, which is involved in thrombolysis. During last two decades, the role of tPA in brain physiology and pathology has been extensively investigated. tPA is expressed in brain regions such as cortex, hippocampus, amygdala and cerebellum, and major neural cell types such as neuron, astrocyte, microglia and endothelial cells express tPA in basal status. After strong neural stimulation such as seizure, tPA behaves as an immediate early gene increasing the expression level within an hour. Neural activity and/or postsynaptic stimulation increased the release of tPA from axonal terminal and presumably from dendritic compartment. Neuronal tPA regulates plastic changes in neuronal function and structure mediating key neurologic processes such as visual cortex plasticity, seizure spreading, cerebellar motor learning, long term potentiation and addictive or withdrawal behavior after morphine discontinuance. In addition to these physiological roles, tPA mediates excitotoxicity leading to the neurodegeneration in several pathological conditions including ischemic stroke. Increasing amount of evidence also suggest the role of tPA in neurodegenerative diseases such as Alzheimer's disease and multiple sclerosis even though beneficial effects was also reported in case of Alzheimer's disease based on the observation of tPA-induced degradation of $A{\beta}$ aggregates. Target proteins of tPA action include extracellular matrix protein laminin, proteoglycans and NMDA receptor. In addition, several receptors (or binding partners) for tPA has been reported such as low-density lipoprotein receptor-related protein (LRP) and annexin II, even though intracellular signaling mechanism underlying tPA action is not clear yet. Interestingly, the action of tPA comprises both proteolytic and non-proteolytic mechanism. In case of microglial activation, tPA showed non-proteolytic cytokine-like function. The search for exact target proteins and receptor molecules for tPA along with the identification of the mechanism regulating tPA expression and release in the nervous system will enable us to better understand several key neurological processes like teaming and memory as well as to obtain therapeutic tools against neurodegenerative diseases.

• The Korean Journal of Physiology and Pharmacology
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• v.21 no.5
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• pp.475-485
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• 2017

The present study aimed to explore the neuroprotective effect and possible mechanisms of rhGLP-1 (7-36) against transient ischemia/reperfusion injuries induced by middle cerebral artery occlusion (MCAO) in type 2 diabetic rats. First, diabetic rats were established by a combination of a high-fat diet and low-dose streptozotocin (STZ) (30 mg/kg, intraperitoneally). Second, they were subjected to MCAO for 2 h, then treated with rhGLP-1 (7-36) (10, 20, $40{\mu}g/kg$ i.p.) at the same time of reperfusion. In the following 3 days, they were injected with rhGLP-1 (7-36) at the same dose and route for three times each day. After 72 h, hypoglycemic effects were assessed by blood glucose changes, and neuroprotective effects were evaluated by neurological deficits, infarct volume and histomorphology. Mechanisms were investigated by detecting the distribution and expression of the nuclear factor erythroid-derived factor 2 related factor 2 (Nrf2) in ischemic brain tissue, the levels of phospho-PI3 kinase (PI3K)/PI3K ratio and heme-oxygenase-1 (HO-l), as well as the activities of superoxide dismutase (SOD) and the contents of malondialdehyde (MDA). Our results showed that rhGLP-1 (7-36) significantly reduced blood glucose and infarction volume, alleviated neurological deficits, enhanced the density of surviving neurons and vascular proliferation. The nuclear positive cells ratio and expression of Nrf2, the levels of P-PI3K/PI3K ratio and HO-l increased, the activities of SOD increased and the contents of MDA decreased. The current results indicated the protective effect of rhGLP-1 (7-36) in diabetic rats following MCAO/R that may be concerned with reducing blood glucose, up-regulating expression of Nrf2/HO-1 and increasing the activities of SOD.

• Journal of Chest Surgery
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• v.41 no.6
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• pp.718-723
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• 2008

Background: The advances in surgical techniques, anesthesia management, perfusion methodology and postoperative intensive care have markedly decreased the mortality and cardiac morbidity of patients who undergo heart surgery over the past 2 decades. Nevertheless, it is well recognized that cardiac surgery carries a substantial risk for central nervous system complications. This study was conducted to evaluate the prevalence of subclinical cerebrovascular lesions in the head and neck by performing magnetic resonance angiography (MRA), and we investigated the clinical course of patients who had abnormal lesion seen on head and neck MRA. Material and Method: The subjects were 107 patients (71 men and 36 women ranging in age from 21 to 83 years) who were scheduled for cardiac surgery under nonemergency conditions between October 2005 and June 2008. Informed consent was obtained before the MRA. The carotid arteries, intracranial arteries and brain parenchyme were examined for subclinical cerebrovascular lesions by performing MRA. We reviewed the patients' medical records and MR findings to evaluate the prevalence of neurologically high risk patients and their clinical course. Result: The overall prevalence of neurologically high risk patients was 15.7% (17 patients). Among these patients, 11 patients had ischemic heart disease and 6 patients had valvular heart disease. Only 2 patients had a history of cerebrovascular disease. The clinical courses of 14 patients (13.1%) were changed according to their MRI findings. Conclusion: The prevalence of subclinical cerebrovascular disease in patients who were scheduled for cardiac surgery was higher than was expected. MR angiography was of value to identify these patients.

• The Journal of Internal Korean Medicine
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• v.21 no.1
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• pp.116-125
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• 2000

Objectives : The aim of this study is to investigate that Sunghyangjeongki-San which has been frequently medicated in the early stage of stroke can protect against ischemic damage in rat brain Methods : Extracellular levels of amino acids(glutamate, aspartate, GABA, glycine, taurine, tyrosine, alanine), organic acids(pyruvate, lactate), and cerebral infarction volume were measured at the striatum of rats subjected to permanant focal cerebral ischemia induced by 2 hours of middle cerebral artery occiusion(MCAO). Rats were orally administered with Sunghyangjeongki-San at 30mins before MCAO and the microdialysate was collected by intracerebral microdialysis three times before MCAO and six times after MCAO at 20mins interval and analyzed by HPLC. After a microdialysis study, the brain was sliced and stained with cresyl violet buffer for the measurement of cerebral infarcted area and volume by image analyzer system Results : The concentrations of glutamate, aspartate, and tyrosine known as excitatory neurotransmitters were significantly decreased in Sunghyangjeongki-San group compared with control group, The concentrations of GABA, glycine, taurine and alanine known as inhibitory neurotransmitters were significantly increased in Sunghyangjeongki-San group compared with control group. The concentrations of pyruvate and lactate showed little significant change in Sunghyangjeongki-San group compared with control group. The measurement of cerebral infarcted area and volume by image analyzer system were significantly decreased in Sunghyangjeongki-San group compared with control group. Conclusions : Sunghyangjeongki-San can affect on protecting against cerebral ischemia by regulating extracellular levels of excitatory and inhibitory amino acid neurotransmitters and improve the conditions of the patients in the early stage of stroke.

• The Journal of Internal Korean Medicine
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• v.19 no.1
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• pp.301-317
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• 1998

A clinical analysis was carried out for 32 patients who were treated in Dept. of Dong-shin Oriental Medicine Hospital from 10st January to 16st May in 1998 and ruled out as dememtia. The results were summarized as follows. 1. In the distribution of sex, female was more than male. And the age of seventies(17 cases, 53.125%) was highest in the frequency of age. 2. In the distribution of having history of drinking and smoking were each 4 cases(12.5%) and 7 cases(21.875%). 3. In the distribution of seasons, the ratio of spring and winter were each 16 cases(50.0%), 15 cases(46.875%), that of summer and fall were comparatively low. 4. In the period from onset to admission, the period within a week had 20 cases(62.5%) as top, and the most period of treatment was 2 and 3 weeks(28.125%). 5. The number of cases that had preceding disease was 35 cases(71.875%), a major portion of preceding diseases were hypertension, diabetes mellitus, stroke. 6. The most common symptom was disorientation(78.125%), and the next common symptom was motor desability(71.875%), and memory disturbance, verbal disturbance was each 59.375 and 47.1%. 7. In the distribution of the CT scan films, 15 cases(46.875%) showed cerebral infarction and that of another 5cases (15.625%) showed cerebral hemorrhage, that of another 2 cases(6.25%) showed brain atrophy. 8. In the lipid density of blood, T-Cholesterol, TG, HDL-Cholesterol, LDL- Cholesterol was within normal limit. 9. In the MMSE-K, the most score was from 16 point to 20 point, and second only was from 11 point to 15 point, and the next was from 6 point to 10 point. 10. In the Ischemic score, 20 cases(62.5%) was diagnosed as brain vascular type dementia, and mixed type dementia was 9 cases(28.125%), Alzheimer type dementia was 3 cases(9.375%). 11. The most used recipes were a sort of recipes to activate of flow the vital energy and the blood, to remove the phlegm(41 cases 33.9%), especially DODAMHOALHEL TANG (12 cases, 9.9%), ANSINCHUNGNOITANG (8 case, 6.6%) was the most used recipe. 12. In the judgement of efficacy, 17 cases(53.125%) showed excellent efficacy, 10 cases(31.25%) showed good efficacy, 5 cases(15.625%) showed no change and that according to MMSE-K, 4 case(18.18%) showed excellent efficacy, 15 cases(68.18%) showed good efficacy, 15 cases(68.18%) showed no change.

• Journal of Oriental Neuropsychiatry
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• v.21 no.1
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• pp.59-69
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• 2010

Objectives: The study aims to look into how the application of EA(Electro-acupuncture) in the initial step of ischemic brain injury affects the changes in Bax and Caspase-3 expression among forebrain apoptosis. Methods: It caused GI by using common carotid artery occlusion and conducted the test by dividing into the no applied EA group after 6 hours and 12 hours, the LI 4 EA group that applied EA to LI4, and GV 20 EA group that was applied to GV 20. After that, the following results were obtained by comparing Bax and Caspase-3 expression, which were apoptosis-related factors, with its application time through immunohistochemical staining after extracting brain of each group. Results: According to each group's Bax expression by the application time, the order of expression increase after 6 hours is shown to be the no applied EA group, LI 4 group, and GV 20 group. The stimulation after 12 hours was most lowly expressed in the GV 20 group, and the no applied EA group and LI 4 group showed similar level. Conclusions: EA stimulation in the initial step after ischemia seems to affect positively Bax and Caspase-3 expression that are index of forebrain apoptosis.

• Journal of agriculture & life science
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• v.46 no.6
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• pp.137-146
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• 2012

This study investigated whether ferulic acid modulates the heme oxygenase (HO)-1 and HO-2 expression in middle cerebral artery occlusion (MCAO)-induced brain injury. Rats (Sprague-Dawley, male) were treated with vehicle or ferulic acid (100 mg/kg, i.v.) before MCAO, and cerebral cortex tissues were collected 24 h after MCAO. This study clearly confirmed the protective effects of ferulic acid during MCAO-induced damage using hematoxylin and eosin staining. MCAO induces nuclear chromatin condensations and necrotic changes with scalloped shrunken form. However, ferulic acid prevented MCAO-induced histopathological changes. HO-1 and HO-2 expression levels were measured using reverse-transcription PCR and Western blot analyses. HO-1 levels were decreased in vehicle-treated animals after MCAO, whereas this decrease in HO-1 levels was attenuated by ferulic acid treatment. However, the level of HO-2 was consistently maintained in the cerebral cortex of vehicle- and ferulic acid-treated animals after MCAO. These results demonstrated that ferulic acid regulates HO-1 expression in ischemic brain injury, while ferulic acid do not modulate HO-2 expression in MACO. In conclusion, these findings suggest that ferulic acid exerts a neuroprotective effect by preventing the MCAO-induced decrease of HO-1 expression.