Protective Effects of Fenofibrate Against the Inflammatory Cytokines in Lipopolysaccharide-Induced Mice Brain Tissues

BACKGROUND: Increasing evidence suggests that the entry of proinflammatory factors into the brain induces the activation of microglia, astrocytes, and oligodendrocytes and then produces the more proinflammatory cytokines and reactive oxygen species that can ultimately lead to neuronal death. This has clinical implications and provides a link between periperal inflammation and neuroinflammation. Peroxisome proliferator-activated receptors (PPARs), a member of the nuclear hormone receptor superfamily, has been implicated in the regulation of immunity and inflammation in rodents and humans. The objective of this study was to investigate whether the increased expression of PPAR with fenofibrate treatment was altered in the immune system of mice brain tissue after Lipopolysaccharide (LPS) was injected intraperitoneally. METHODS: PPARs expression was investigated in the brain tissues of BalB/c mice (n=6) under four situationssterile saline injection (control), LPS injection to generate periperal inflammation, LPS injection (5 mg/kg) with pretreated fenofibrate, and fenofibrate injection (100 mg/kg). RESULTS: Fenofibrate has protective effects against the increase of LPS-induced proinflammatory cytokines including interleukin (IL)-1beta, IL-6, and tumer necrosis factor-alpha in serum and brain tissue, measured using the enzyme linked immunosorbent assay, reverse transcriptase-polymerase chain reaction, and Western blot analysis. Also fenofibrate pretreatment markedly suppressed the reduction of PPARs mRNA and protein level by LPS injection. Moreover, the increased activation of PPARs abrogated the reduction of ABCD3, ACOX1, and catalase expression leading to an increase in the antioxidative capacity in brain tissue blocking the production of lipid peroxidation after LPS administration. CONCLUSION: The antiinflammatory and antioxidative properties of fenofibrate may be useful in ameliorating the progression of neuronal diseases.

Glutamate Induces Endoplasmic Reticulum Stress-Mediated Apoptosis in Primary Rat Astrocytes

BACKGROUND: Glutamate is a well-known central nervous system (CNS) excitatory neurotransmitter that plays a role in memory and learning. However, in excess, it leads to a process called excitotoxicity resulting in cell death. To investigate the mechanism of glutamate cytotoxicity, the apoptosis signaling pathway of primary rat astrocytes was explored in vitro. With this study, we hope to improve the prevention and treatment of ischaemic strokes and various central nervous system disorders. METHODS: To produce a model of cell injury, primary rat astrocytes were treated with glutamate. RESULTS: Treatment with glutamate induced death by apoptosis in primary rat astrocytes. This was evidenced by an increase in sub-G0/G1 fraction of the cell cycle with a loss of cell viability. Glutamate also increased the intracellular accumulation of Ca2+ ions, the expression levels of glucose-regulated protein 78 (Grp78) and C/EBP homologous protein (CHOP) protein, and the phosphorylation of protein kinase r-like endoplasmic reticulum kianse (PERK). However, the expression pattern of activating transcription factor (ATF)4 protein did not change and the 90 kDa ATF6 was cleaved to 50 kDa along with a reduced amount of Bcl-2 protein in a time-dependent manner. Interestingly, pre-treatment with glutathione markedly suppressed the reactive oxygen species (ROS) generation and the sub-G0/G1 fraction. However, the intracellular concentration of Ca2+ did not change. CONCLUSION: Our findings suggest that glutamate injures primary rat astrocytes through the endoplasmic reticulum (ER) stress-mediated apoptotic signaling pathway, as well as, ROS generation. More specifically, through Grp78, PERK, and CHOP, glutamate activates the ER stress-mediated signaling pathway in astrocytes and activates ATF6 to reduce the expression of the Bcl-2 proteins contributing to apoptosis. In addition, the ER stress-mediated signaling pathway is closely related to the transformation of intracellular ROS. This information should be applied to research for the prevention and treatment of strokes and other CNS conditions.

The Benefit of Further Tests for Patients Presenting to the Emergency Department with Non-Specific Abdominal Pain

PURPOSE: Acute abdominal pain is the most common cause of visits to the emergency department (ED). Among these visits, 30% of patients have non-specific abdominal pain (NSAP). Although the actual number of such patients is large, there are few studies of NSAP. Our report is about the usefulness of results from additional diagnostic tests for patients who have NSAP. METHODS: Subjects in our study were patients who presented at our ED between January 1, 2007 and December 31,2008 with NSAP. We retrospectively investigated the relevance of several factors including general patient characteristic, associated symptoms, pain site, existence of tenderness, and whether additional diagnostic tests were done. RESULTS: A total of 470 patients visited our ED during the study period and 148 of them had additional tests. Among the 148 patients who had additional tests, 48 had an important change in their treatment plan. Abdominal-pelvic computed tomography scans were a most useful tool in plan change (in 37 patients). Diseases that changed the treatment plan included fatal diseases such as abdominal aortic dissection and pan-peritonitis. CONCLUSION: Among patients with NSAP, carrying out of additional diagnostic tests led to important changes in the treatment plan. Abdominal-pelvic CT scans were a useful diagnostic tool. Therefore, close observation of NSAP patients is necessary and it is clinically useful to carry out additional diagnostic tests to see if the patient's symptoms and signs are changing.

Immunohistochemical Study of the Expression of pERK1/2 Protein in the Forebrains of Adult Rodents Following Hypoxia-ischemia injury

PURPOSE: The purpose of this study was to evaluate spatiotemporal evaluation of pERK1/2 protein expression in the forebrain following hypoxic-ischemic (HI) injury in adult Sprague-Dawley rats. METHODS: HI injury was induced by occlusion of the bilateral common carotid artery (CCA) and respiration with 5% O2 hypoxic gas for 8 minutes, followed by unilateral release of CCA. RESULTS: Immunoreactivity for pERK1/2 protein in the bilateral cortex began to increase at 2 hours, reached peak levels at 6 hours, and then decreased by 24 hours after HI injury. In a cortical neuron, the expression of pERK1/2 protein was observed in all cellular components and processes including dendrites, cell body and nuclei at 6 hours, but persisted only in the cell body by 24 hours after HI injury. Temporal changes in the immunoreactivity for pERK1/2 protein in the hippocampus was very similar to that of the cortex following HI injury. In contrast, the temporal changes in the cellular distribution of pERK12 protein in hippocampal neurons was largely different from that of the cortex following HI injury. CONCLUSION: The results of the present study suggest that HI injury causes an early activation of ERK1/2 signaling with a differential cellular distribution of pERK1/2 protein among different forebrain structures. Further study needs to be done in order to elucidate a possible role of ERK1/2 signaling for neural damage in the adult rodent HI model.

Plasma Neuron-specific Enolase and Glutamic Acid Level in Acute Ischemic Stroke

PURPOSE: We studied the plasma neuron-specific enolase (NSE) and glutamic acid levels as a marker of the severity of acute ischemic stroke (AIS). METHODS: We enrolled 93 patients who visited to the emergency department from April to September, 2005. The AIS patients included those who visited the emergency department within 24 hours due to ischemic stroke symptoms. The AIS patients was subclassified according to large-vessel, small-vessel, cardioembolic, or unclassified infarction. RESULTS: The plasma NSE and glutamic acid level were 15.1+/-7.9 ng/ml and 204.5+/-86.5 nM/ml, respectively, in the AIS patients. Plasma NSE and Glutamic acid in the was higher than reference range (NSE 0-12 ng/ml, Glutamic acid 0-130 nM/ml). According to the type of infarction, no differences were observed in the plasma NSE and glutamic acid levels. CONCLUSION: In cases of AIS, NSE and glutamic acid have no statistical usefulness in classifying the type of infarction. However, the value of plasma NSE and glutamic acid levels have statistical usefulness in deciding on the existence or nonexistence of an AIS.

Immunohistochemical Study for Expression of cFos, pERK1/2 and pAkt Proteins in a Macrosphere Animal Model for Permanent Focal Brain Ischemic Injury

PURPOSE: Recently, a new animal model for permanent focal brain ischemia using macrospheres was developed wherein the hypothalamic area was free from ischemic injury. The purpose of this study was to evaluate spatiotemporal changes in the expressions of cFos, pERK, and pAkt proteins in the macrosphere model. METHOD: Three or four macrospheres were injected into the internal carotid artery after ligation of the external carotid artery to induce permanent focal brain ischemic injury. RESULT: Twenty-four hours after macrosphere injection, 2,3,5-Triphenyltetrazlium (TTC) staining showed a marked ischemic injury in the blood supply territory of the middle cerebral artery, for example, the cerebral cortex and striatum. Furthermore, TUNEL staining revealed apoptotic cell death in the ischemic injury region of the cerebral cortex and striatum. Expression of the cFos protein was significant in the penumbral zone, but not in the ischemic core of the cortex and striatum, two and six hours after ischemic insult. A transient prominent expression of the pERK1/2 protein was noted in the penumbral zone of the cortex and striatum two hours after injection of macrospheres. In contrast, there was a strong immunoreactivity for the pAkt protein in the ischemic core, but not in the penumbral zone of the cortex and striatum, six hours after ischemic injury. CONCLUSION: The above results suggest that early expressions of cFos, pERK1/2, and pAkt proteins take part in different signaling cascades for cell survival or death in macrosphere animal model of permanent focal brain ischemic injury.

Plasma Homocysteine Level and Blood Coagulation Factors in Acute Ischemic Cerebral Stroke

PURPOSE: We studied the plasma homocysteine level and coagulation factors such as fibrinogen and antithrombin III (ATIII) in acute cerebral infarction (ACI). METHODS: We enrolled 222 patients who visited our emergency department from March 1, 2003, to August 31, 2003. The ACI patient group included those who visited the emergency department within 24 hours due to cerebral infarction symptoms and included 115 patients the control group included those visited the emergency department due to minor trauma (CRAMS score>9) and include 56 patients in the homocysteine control group and 51 in the fibrinogen and ATIII group. ACI patient group was subclassified according to great artery, small artery, or cardioembolic cerebral infarction. RESULTS: The plasma homocysteine level, the fibrinogen, and ATIII were 16.3+/-7.9 micrommol, 283.2+/-60.1 mg/dl, 87.3+/-25.8%, respectively, in the ACI patient group and 9.6+/-4.0 micrommol, 245.3+/-62.2 mg/dl, 109.8+/-14.7% in the control group. The values of plasma homocysteine and fibrinogen in the was higher than it was in the control group. The value of ATIII in the ACI patient group was lower than it was in the control group. In according to cerebral infarction type, no differences were observed in the plasma homocyteine, fibrinogen, and ATIII. CONCLUSION: In cases of acute cerebral infarction, fibrinogen and ATIII have no statistical usefulness in classifying the type of cerebral infarction. However, the value of plasma homocysteine, fibrinogen, and ATIII have statistical usefulness in deciding on the existence or nonexistence of an acute cerebral infarction.

Expressions of the pERK1/2 and the cFos Proteins at an Early Stage of Transient Global Ischemia-reperfusion Injury in the Hippocampus of Rats

PURPOSE: This study was to evaluate temporal changes in the expressions of the phosphorylated extracellular-regulated kinase1/2 (pERK1/2), the phosphorylated MAPK/ERK kinase1/2 (pMEK1/2) and the cFos proteins in the hippocampus of rats following transient global ischemia. METHODS: Transient global ischemia was induced in the forebrains of Sprague-Dawley rats by using a 4-vessel occlusion for 20 min under anesthetic condition. Hematoxyline-eosin staining showed typical microscopic findings that represented neuronal cell death in hippocampal CA1 regions 5 days after transient global ischemia. Four-vessel occlusion-reperfusion produced ischemic injury in major forebrain structures, such as the striatum, the cortex and the hippocampus, in the finding of triphenyltetrazolium chloride (TTC) staining. RESULTS: A high density of pERK1/2 immunoreactivity existed in the pyramidal-cell layers of the CA2-3 regions and in the granular-cell layers of the dentate gyrus 5 min after ischemia. Following ischemia, expression of the pMEK1/2 protein showed temporal changes similar to that of the pERK1/2 protein. A significant expression of the cFos protein was noted in the pyramidal-cell layers of the CA2-3 regions and in the granular-cell layers of the dentate gyrus 2 hours after global ischemia. CONCLUSION: Intracellular signaling cascades of the ERK or the cFos protein take part in early cellular events in the hippocampus of rats in response to ischemic insult.

Effect of Melatonin on Expression of c-Jun Proteins and BDNF mRNA in Transient Global Ischemia-Reperfusion Injury of Rat Brain

PURPOSE: The purpose of this study was to investigate the effect of systemic treatment of melatonin known as a potent free radical scavenger on expression of c-Jun proteins and brain-derived neurotrophic factor (BDNF) mRNA in transient global ischemia-reperfusion injury of rat brain. METHODS: Spargue-Dalwey rats were used and divided into three groups: ischemia group, ischemia group pretreated with melatonin, ischemia group posttreated with melatonin. Brain ischemia-reperfusion injury induced by occlusion of bilateral carotid and vertebral arteries (4-vessel occlusion) for 15 min followed by recirculation of cerebral blood flow. Animals were received intraperitoneal injection of melatonin (10 mg/kg) either 30 min before ischemia (pretreatment) or 0 min after reperfusion (posttreatment). Four vessel occlusion-reperfusion produced ischemic injury in major forebrain structures such as striatum, cortex, hippocampus in the finding of triphenyltetrazolium chloride (TTC) staining. Spectrophotometric assay for formazan, an end-product of TTC showed increased value of formazan formation in ischemic area of the brain posttreated with melatonin 24 hours after the ischemia-reperfusion injury. RESULTS: Posttreatment with melatonin caused a significant decreased in number of c-Jun immunoreactive neurons in CA1 region of the hippocampus after ischemia-reperfusion insult. Furthermore, autoradiographic density for BDNF mRNA in the hippocampus and cortex was increased by systemic treatment with melatonin especially in posttreatment group. CONCLUSION: These results suggest that melatonin treatment results in an attenuation of ischemic damage caused by ischemia-reperfusion in nueronal cells of the sensitive areas of rat brain.

Clinical Analysis of Attempted Suicide in the Elderly

BACKGROUND: Despite the high suicide rate among the elderly, there is a relative lack of information on the outcomes for elderly people who have attempt suicide. METHODS: The authors performed a retrospective analysis of 260 elderly suicide cases observed in the WonKwang University Hospital Emergency Center from January, 1997 to December, 2000. RESULTS: 1) The male-to-female ratio was 1.71:1. 2) The major cause of the attempt was chronic pain or disease. 3) Poisoning was the most common method of suicidal attempt. 4) The mortality rate was 23.1%. CONCLUSION: Chronic pain or disease in the elderly indicates the need for mental health services.

Clinical Analysis of Patients with Acute Dizziness Visiting an Emergency Center

BACKGROUND: Dizziness is a common complaint in patients presenting at emergency departments. Dizziness is difficult to assess because it is a subjective complaint that cannot be measured. We report a clinical analysis of patients with acute dizziness: type, duration, symptom, incidence, etc. METHODS: We reviewed the clinical details and the results of vestibular function tests for 106 acutely dizzy patients who visited the Emergency Department of Wonkwang University Hospital during the period of Jul. 1999 through Dec. 1999. RESULTS: The most common etiology of acute dizziness was the peripheral vestibular system(66%). The most common disease of the peripheral vestibular system was benign paroxysmal positional vertigo(52.9%), and the second most one was vestibular neuronitis(42.9%). In the central nervous system, cerebrovascular accident(63.6%) was the most common cause. All of the patients had experienced a previous vertigo attack, and 42.4% of them had frequent attacks. Dizziness of the cochlear systems were usual in peripheral vertigo. The usual underlying diseases related with vertigo were hypertension, cerebral infarction and diabetes mellitus. CONCLUSION: Dizziness is a complex and frustrating symptom with numerous possible causes. In case with suspected central disorders, CT and MRI have a great diagnostic significance.

Clinical Analysis of the Suicidal Attempters Visiting Emergency Center

BACKGROUND: To collect the data related to the clinical analysis of suicidal attempters who visited the emergency center of WonKwang University Hospital. METHODS: The authors performed a retrospective analysis of 306 suicide attempters, observed in the WonKwang University Hospital Emergency Center from January 1st, 1998 to December 31th, 1998. RESULTS: 1) Factors related to increased occurrence were male(1.1:1), age of 2nd, 3rd & above 6th decade. 2) Poisoning was the most common method of suicidal attempt(90.8%). 3) The average observation time was 18.76+/-23.3 hour and average staying time in admitted patients were 40.4+/-32.3 hour. 4) Mortality rate was in male 23.1%(37/160) and in female 10.0%(15/146). 5) Among the suicidal attempters who admitted, 56 patients were admission(11.8%). 6) Consultant of neuropsychiatric department was only 10.5%(18/172), and most common underlying psychiatric disorder was depression(10/18). CONCLUSION: 1) To develope observation room decrease staying time in suicidal attempters. 2) All suicidal attempters were necessarily neuropsychiatric consultant and continuously follow-up.

Aneurysm of Splenic Artery: A Case Report

Aneurysm of the splenic artery are the third most common intra-abdominal aneurysm, following aneurysms of the infrarenal aorta and iliac arteries. Splenic artery aneurysms (SAA) are the most frequent visceral artery aneurysms and account for more than two thirds of all lesions. Incidence of SAA are rare clinical entities(0.01-0.2%) that carry risk of rupture and fatal hemorrhage(35-100%). Fibroblastic dysplasia and atherosclerosis is fecund in the majority, and the fact that these aneurysms developes more commonly in female. Most patients are asymptomatic and the diagnosis is generally made incidentally. The treatment of patient with known SAA is dictated by several factors, including location, age, sex, present of symptom, size, pregnancy. We report ruptured splenic artery aneurysm with hemoperitoneum and review of the literature.

Clinical Analysis of the Pediatric Death Patients Visiting Emergency Center

BACKGROUND: To collect the data related to the prevention of death in pediatric patients in the emergency center, the authors made a clinical analysis of pediatric death patients who visited the emergency center of Wonkwang University Hospital. METHODS: The authors performed a retrospective analysis of 49 pediatric deaths under the age of 16 years, observed in the Wonkwang University Hospital emergency center from January 1st, 1995 to December 31th, 1996. RESULTS: 1) Among a total of 49 pediatric patients who died (24 patients in 1995 and 25 patients in 1996), 19 patients were dead on arrival and 30 were died after arrival. 2) The cause of death of all the patients of 1 to 5 years old was the accident, and that of the majority patients of less than 1 year was disease. 3) We observed the diurnal variation in pediatric death and the rate was higher between 12:00 to 6:00. P.M. 4) Iksan city was the most common place of residency of the patients(71.4%) 5) 36 patients (73.5%) died from traffic accidents and 29 of them were victims of pedestrian traffic accidents. 6) The most common cause of death in accidents was head injury(54%). CONCLUSION: The majority of the pediatric death patients observed in our emergency center was involved in pedestrian traffic accident, head injury, so we conclude that team approach with pediatric trauma specialist could decreased unwanted pediatric deaths.

Immunohistochemical Study for Expression of cFos-like Protein Induced by Acute Hypotension in Rat Brain

BACKGROUND: It has been well known that cFos protein, one of the immediate-early gene proteins, was a cellular marker to characterize physiological or anatomical property of neural networks in mammalian brain. The purpose of this study was to evaluate quantitative change of cFos protein expression in rat brain nuclei concerned with regulation of blood pressure according to severity of hypotension and compare the spatial pattern of cFos between hemorrhagic hypotension and non-hemorrhagic hypotension elicited by vasodilatation. METHODS: The mean blood pressure (MBP) in the femoral artery was recorded by using pressure transducer and polygraph. Nitroprusside was injected into the femoral vein with constant flow rate by means of osmotic pump in which the dosage was 5microgram Per kg a minute. Immunohistochemical staining was Performed by using conventional ABC method to visualize cFos-like immunoreactive (cFLI) neurons in many brain nuclei and FLI cells were counted by image analyser. RESULTS: Mild hemorrhage group with MBP of 70-80 mmHg showed significant increase of cFLI expression in the paraventricular nuclei and supraoptic nuclei. In contrast, severe hemorrhage group with MBP of 50 mmHg increased significantly cFLI expression in the rostral ventrolateral medulla, periventricular thalamic nucleus, central gray matter, medial vestibular nuclei as well as the nuclei seen in mild hemorrhage group. Nitroprusside induced hypotension exhibited a similar spatial pattern of ctrl expression to severe hemorrhage group. CONCLUSION: These results suggest that severe reduction of blood pressure induces expression of cFLI neurons in the neural network systems that control vital organs.

Effects of Stress induced by Traffic Accidents on the Blood Concentrations of Cortisol, Glucose and Cytokines

BACKGROUND: Traffic accident is a catastrophic event which induces severe stress to the victims. According to psychoneuroimmunolgic studies, the stress induced by traffic accident may affect emotion, neuroendocrine and immune systems. This study was designed to investigate what is the effect of the stress induced by traffic accident on the secretions of cortisol, IL-1alpha and IL-6 and the relationship with blood levels of glucose and lactic dehydrogenase in the traffic accident victims. METHODS: Thirty five traffic accident victims and eleven normal healthy control persons were included in this prospective, randomized study. Ten milliliters of blood were drawn at 1hr and after 12hr after trauma from the victims and normal control to evaluate the parameters. RESULTS: The level of cortisol was significantly different between traffic accident patients(115.181microgram/ml) and normal healthy control(39.10microgram/ml) after 12hrs (p<0.05). There were significant differences at the level of glucose(control: 139.7mg/ml;patient: 75.2mg/ml) and IL-6 (control: 1.01pg/ml; patient: 238.46pg/ml) between control and traffic accident patients at 1hr. CONCLUSION: This results suggested that the secretion of cortisol, IL-6, and the blood levels of glucose were markedly changed by the stress of traffic accident.

Involvement of Fibronectin in the Migration of Macrophage and Expression of Nitric Oxide Synthase in the BCG induced Inflammatory Sites in Rat Bladder / 대한면역학회지

No abstract available.

Changes of motor evoked potentials and spinal cord evoked potentials following spinal cord injury in rats

No abstract available.

Clinical analysis of head trauma

No abstract available.

Clinical observation of acute drug intoxication

No abstract available.