• Journal of The Korean Society of Clinical Toxicology
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• v.9 no.1
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• pp.20-25
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• 2011

Purpose: This study was designed to analyze the contributing factors, as well as the incidence and nature of the cardiac toxicity, in patients presenting with diphenhydramine overdose. Methods: We retrospectively reviewed the medical records of the intoxicated patients who presented to the ED of Korea University Anam Hospital from January 2008 to December 2010. Those patients who visited due to a diphenhydramine overdose were selected and the following features were recorded for analysis: the general characteristics, vital signs, the amount of ingested diphenhydramine, the time interval from ingestion to presentation, the coingested drugs (if any), the toxicities and the ECG findings. Cardiac toxicity, while defined mainly in terms of the temporary ECG changes such as QTc prolongation, right axis deviation, QRS widening, high degree AV block and ischemic changes, also encompassed cardiogenic shock, which is a clinical finding. Results: A total of eighteen patients were enrolled. Of the eighteen patients, eight had ingested diphenhydramine only, while ten had ingested other drugs in addition to diphenhydramine. The most commonly observed toxicity following diphenhydramine overdose included cardiac toxicity (78%). Cardiac toxicity was observed in all the patients who presented to the emergency department 2 hours after ingestion. The patients with QTc prolongation turned out to have ingested significantly larger amounts of diphenhydramine. Conclusion: QTc prolongation and right axis deviation were common findings for the patients with a diphenhydramine overdose. QTc prolongation was more likely to occur with ingesting larger amounts of diphenhydramine. Close monitoring is mandatory for patients who have ingested large amounts of diphenhydramine to prevent such potentially lethal cardiac toxicity.

• Journal of Veterinary Clinics
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• v.29 no.5
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• pp.372-376
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• 2012

Acute kidney injury (AKI) is a serious problem associated with high morbidity and mortality. Ischemia-reperfusion is an important cause of acute kidney injury. This study was performed to ascertain clinically useful biomarkers for the diagnosis of AKI. In three miniature pigs, AKI were induced by 60 minutes of bilateral renal ischemia by the clamping renal artery. Blood and urine samples were collected from the pigs prior to clamping (baseline) and 0, 1, 3 and 5 days post-clamping. Serum blood urea nitrogen (BUN), creatinine, sodium and uric acid were measured in serum and urine samples. Fractional excretion of sodium ($FE_{Na}$) and fractional excretion of uric acid ($FE_{UA}$) were calculated. Also, interleukin (IL)-6, IL-18, liver type fatty acid binding protein (L-FABP) and glutathione-S-transferase (GST) were detected by Western immunoblotting. Serum BUN and creatinine levels were increased significantly at day 1 post-clamping in all three miniature pigs. However, $FE_{Na}$ and $FE_{UA}$ showed marked individual differences. Western immunoblotting revealed significantly increased levels of IL-6, IL-18, L-FABP and GST in post-ischemic urine, compared to pre-clamping. While more research concerning the variance of $FE_{Na}$ and $FE_{UA}$ is needed, serum BUN, creatinine, IL-6, IL-18, L-FABP and GST may be sensitive urine biomarkers for diagnosis of AKI together with other biomarkers in the porcine ischemia-reperfusion model.

• Korean Journal of Acupuncture
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• v.22 no.3
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• pp.137-156
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• 2005

Objectives : Cnidium officinale(CO) has been used for medication for stroke in the Oriental Medicine. So this study was planned to investigate the effects of CO on the focal ischemia-induced by Middle Cerebral Artery Occlusion(MCAO) in rats Materials and methods : The focal ischemia was induced by MCAO. CO extracts through oral administration and herbal acupuncture at GB2l was carried out during 3 weeks after focal ischemia-induced. Eight-arm radial maze was used for the behavioral task. For the neuroprotective effect of CO, we investigated AchE, ChAT, and NGF-expression by immnohistochemical method. Results : The error rate in the eight-arm radial maze task was significantly decreased in normal group compared to control group on 1-6days, OA-CO1(CO oral administration, 0.8g/kg) group on 1-6days, OA-CO2(CO oral administration, 1.6g/kg) group on 1-3,5,6days, HA-CO1(CO herbal acupuncture, 0.016g/kg) group on 2,3,6days, HA-CO2(CO herbal acupuncture, 0.008g/kg) group on 1-3,5,6days. The rate of correct choice was significantly increased in OA-CO1, HA-CO2. The density of neurons in the hippocampal CA1 was the most increased in OA-CO1, HA-CO1, HA-CO2. The density of ChAT in the hippocampal CA1 was increased in OA-CO1, HA-CO2. The density of ChAT in the hippocampal CA1 was significantly increased in OA-CO1, HA-CO2. The density of NGE in the hippocampal CAI was significantly increased in OA-CO1, OA-CO2, HA-CO2. Conclusions : These results suggest that CO oral administration with 0.8g/kg and CO herbal acupuncture with 0.008g/kg might be used as a regulator of cell death of cholinergic system induced by stroke.

• Korean Journal of Acupuncture
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• v.22 no.4
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• pp.67-81
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• 2005

Objectives : Cervus Elaphus(CE) has been used to medication for ischemic stroke in the Oriental Medicine. So this study was planned to investigate the effects of CE herbal acupuncture therapy(CE-HAT) on the focal ischemia-induced by intraluminal filament insertion in the rats. Materials and methods : The focal ischemia was induced by middle cerebral artery occlusion for 2hours. The groups divided into 6 groups, normal(intachess group), control(no theray group after ischemia-induced), CE-HAT1(Cervus Elaphus-herbal acupuncture therapy group at LR1, HT9 after ischemia-induced), CE-HAT2(Cervus Elaphus-herbal acupuncture therapy group at LU8, KI7 after ischemia-induced), CE-HAT3(Cervus Elaphus-herbal acupuncture therapy group at LR1, HT9, LU8, KI7 after ischemia-induced), CE-HAT4(Cervus Elaphus-herbal acupuncture therapy group at LR1, HT9, HT3, KI10 after ischemia-induced). CE-HAT was carried out during 3 weeks after focal ischemia-induced. Eight-arm radial maze was used for the behavioral task and neuropretective effect of CE-HAT was observed by Cresyl violet, AchE, ChAT-stain. Results : The error rate in the eight-arm radial maze task was significantly decreased in CE-HAT1, CE-HAT2, CE-HAT4 on 3days, CE-HAT4 on 4days, CE-HAT2, CE-HAT4 on 5days, CE-HAT3, CE-HAT4 on 6days. The rate of correct choice was significantly increased in CE-HAT4. The density of neurons in the hippocampal CA1 was significantly increased in CE-HAT1, CE-HAT2, CE-HAT3, CE-HAT4, compared to control group. The density of ChAT in the hippocampal CA1 was significantly increase in CE-HAT4. The density of ChAT in the hippocampal CA1 was significantly increased CE-HAT1. Conrlusions : These results suggest that the Cervus Elaphus-herbal acupuncture therapy could be used as a medication for controlling the stroke induced by deficiency.

• Journal of Life Science
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• v.17 no.7 s.87
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• pp.1019-1022
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• 2007

Thrombolytic therapy with tissue plasminogen activator (tPA) can improve the clinical outcome of ischemic stroke patients. However, its clinical application is limited by narrow therapeutic time windows and elevated risks of cerebral hemorrhage and brain injury. In part, these effects of tPA has been related to matrix metalloproteinase-9 (MMP-9) dysregulation. Here, we investigate that the effects of alteplase (tPA with short half-life) and pamiteplase (a modified tPA with long half-life) on the MMP-9 regulation in neurovascualr unit. The total levels of MMP-2 and MMP-9 in neuronal cells are lower than astrocytes. Alteplase (1-10 ${\mu}g/ml$) induced upregulation of MMP-2 and MMP-9 in rat cortical neurons and astrocytes, respectively. Whereas pamiteplase in a wide range of dose did not affect the MMP-2 and MMP-9 responses in both of cells. These results suggest that pamiteplase with long half-life can be provided as a agent that overcome the side effects of alteplase.

• Molecules and Cells
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• v.20 no.3
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• pp.401-408
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• 2005

Reactive oxygen species (ROS) contribute to the development of various human diseases. Cu,Zn-superoxide dismutase (SOD) is one of the major means by which cells counteract the deleterious effects of ROS. SOD activity is dependent upon bound copper ions supplied by its partner metallochaperone protein, copper chaperone for SOD (CCS). In the present study, we investigated the protective effects of PEP-1-CCS against neuronal cell death and ischemic insults. When PEP-1-CCS was added to the culture medium of neuronal cells, it rapidly entered the cells and protected them against paraquat-induced cell death. Moreover, transduced PEP-1-CCS markedly increased endogenous SOD activity in the cells. Immunohistochemical analysis revealed that it prevented neuronal cell death in the hippocampus in response to transient forebrain ischemia. These results suggest that CCS is essential to activate SOD, and that transduction of PEP-1-CCS provides a potential strategy for therapeutic delivery in various human diseases including stroke related to SOD or ROS.

• The Journal of Korean Medicine
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• v.17 no.1 s.31
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• pp.407-432
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• 1996

Clinical Observation was made on 37 cases of Endotracheal intubation patients in the ICU of Oriental Medical Hosptal of Tae- Jon University from January in 1992 to June in 1995. 1. There were many cases of Endotracheal intubation in ischemic attack hemorragic in order. 2. Cerebral embolism mostly occured in the MCA territory and cerebral thrombosis, ICH, in the pons, generally. 3. On admission the consciousness of the most patients was 3 to 7 point by GCS. 4. The ordinary preceeding disease was hypertension. 5. Most patients were discharged from ICU after 2 days. 5. Most patients were discharged from ICU after 2 days. 6. Endotracheal intubation was done most frequently from 1 p.m. to 3 p.m. and intubated time was less than 2 hours. 7. Endotracheal intubation was done in case of heart arrest than dyspnea cases. 8. The main complication of patients of C.V.A. in ICU were urinary tract infection, pneumonia in order. 9. There were no side effects after and by Endotracheal intubation.

• The Journal of Korean Medicine
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• v.26 no.1 s.61
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• pp.174-186
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• 2005

Objectives : The water extract of Samul-tang (SMT) has traditionally been used for treatment of ischemic heart and brain damage in oriental medicine. However, little is known about the mechanism by which the water extract of SMT rescues cells from these damages. Methods: This study was designed to investigate the protective mechanisms of SMT on oxidative stress-induced toxicity in H9c2 cardiomyoblast cells. Treatment with $H_2O_2$ markedly induced death of H9c2 cardiomyoblast cells in a dose-dependent manner. Results: The characteristics of H20z-induced death of H9c2 showed apparent apoptotic features such as DNA fragmentation and morphological change. However, SMT significantly reduced both H202-induced cell death and morphological change. The decrease of Bc-2 expression by High were inhibited by SMT. In addition, the increase of Bax expression was also inhibited by SMT. The cotreatment of SMT and $H_2O_2$ in H9c2 cells also induced the phosphorylation of ERK in a time-dependent manner. Moreover, PD98059, a specific inhibitor of ERK1/2 attenuated the protective effects of SMT on $H_2O_2-induced$ toxicity in H9c2 cardiomyoblast cells. These results suggest that both ERK1/2 signaling pathways play important roles in the protective effects of SMT on $H_2O_2-induced$ apoptotic death of H9c2 cells. Also, the expression profile of proteins in $H_2O_2$ cardiomyoblast cells were screened by using two-dimensional (2-D) gel electrophoresis. Among 300 spots resolved in 2-D gels, the comparison of control versus apoptosis cells revealed that signal intensity of 17 spots increased and 11 spots decreased. Conclusions: Taken together, this study suggests that the protectiw effects of the water extract of SMT against oxidative damages may be mediated by the modulation of Bc1-2 and Bax expression via the regulation of the ERK signaling pathway.

• The Korean Journal of Physiology and Pharmacology
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• v.15 no.3
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• pp.149-156
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• 2011

Golgi SNAP receptor complex 1 (GS28) has been implicated in vesicular transport between intra-Golgi networks and between endoplasmic reticulum (ER) and Golgi. Additional role(s) of GS28 within cells have not been well characterized. We observed decreased expression of GS28 in rat ischemic hippocampus. In this study, we examined the role of GS28 and its molecular mechanisms in neuronal (SK-N-SH) cell death induced by hydrogen peroxide ($H_2O_2$). GS28 siRNA-transfected cells treated with $H_2O_2$ showed a significant increase in cytotoxicity under glutathione (GSH)-depleted conditions after pretreatment with buthionine sulfoximine, which corresponded to an increase of intracellular reactive oxygen species (ROS) in the cells. Pretreatment of GS28 siRNA-transfected cells with p38 chemical inhibitor significantly inhibited cytotoxicity; we also observed that p38 was activated in the cells by immunoblot analysis. We confirmed the role of p38 MAPK in cotransfected cells with GS28 siRNA and p38 siRNA in the cell viability assay, flow cytometry, and immunoblot. Involvement of apoptotic or autophagic processes in the cells was not shown in the cell viability, flow cytometry, and immunoblot analyses. However, pretreatment of the cells with necrostatin-1 completely inhibited $H_2O_2$-induced cytotoxicity, ROS generation, and p38 activation, indicating that the cell death is necroptotic. Collectively these data imply that $H_2O_2$ induces necroptotic cell death in the GS28 siRNA-transfected cells and that the necroptotic signals are mediated by sequential activations in RIP1/p38/ROS. Taken together, these results indicate that GS28 has a protective role in $H_2O_2$-induced necroptosis via inhibition of p38 MAPK in GSH-depleted neuronal cells.

• Journal of Acupuncture Research
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• v.24 no.2
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• pp.141-153
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• 2007

Objectives: The purpose of this report is to examine the effect of $BL_{66}$ ${\cdot}$ $GB_{43}$ supplement and LIl ${\cdot}$ $GB_{44}$ draining in acupuncture for cerebral apoplexy treatment. Methods : I designed to investigate whether $BL_{66}$ ${\cdot}$ $GB_{43}$ supplement and $LI_1$ ${\cdot}$ $GB_{44}$ draining in acupuncture affects cerebral hemodynamics [regional cerebral blood flow(rCBF), mean arterial blood pressure(MABP)] in normal rats, and to make manifest whether $BL_{66}$ ${\cdot}$ $GB_{43}$ supplement and $LI_1$ ${\cdot}$ $GB_{44}$ draining in acupuncture is mediated by cyclooxygenase or guanylate cyclase. The changes of rCBF and MABP were determinated by laser-doppler flowmetry(LDF). Results : 1. $BL_{66}$ ${\cdot}$ $GB_{43}$ supplement and LI1 ${\cdot}$ $GB_{44}$ draining in acupuncture increased rCBF significantly, but decreased MABP. These results suggest that $BL_{66}$ ${\cdot}$ $GB_{43}$ supplement and $LI_1$ ${\cdot}$ $GB_{44}$ draining in acupuncture increased significantly rCBF by dilating pial arterial diameter(PAD). 2. By pretreatment with indomethacin(1 mg/kg, i.p.), the effect of $BL_{66}$ ${\cdot}$ $GB_{43}$ supplement and $LI_1$ ${\cdot}$ $GB_{44}$ draining in acupuncture induced increase of rCBF was significantly inhibited, the decreased MABP by treatment with $BL_{66}$ ${\cdot}$ $GB_{43}$ supplement and $LI_1$ ${\cdot}$ $GB_{44}$ draining in acupuncture was increased. 3. By pretreatment with methylene blue($10{\mu}/kg$, i.p.), the increased rCBF by treatment with $BL_{66}$ ${\cdot}$ $GB_{43}$ supplement and $LI_1$ ${\cdot}$ $GB_{44}$ draining in acupuncture was decreased conversely, the decreased MABP by treatment with $BL_{66}$ ${\cdot}$ $GB_{43}$ supplement and $LI_1$ ${\cdot}$ $GB_{44}$ draining in acupuncture was decreased. and then increased. Conclusion : I suggest that $BL_{66}$ ${\cdot}$ $GB_43$ supplement and $LI_1$ ${\cdot}$ $GB_{44}$ draining in acupuncture has an anti-ischemic effect through the improvement of cerebral hemodynamics.