Comparison of the response using ICR mice derived from three different sources to multiple low-dose streptozotocin-induced diabetes mellitus / 한국실험동물학회지

This study was conducted to compare the multiple low-dose streptozotocin (MLDS)-induced diabetic patterns of Korl:ICR, A:ICR, and B:ICR mice obtained from three different sources. Six-week-old male ICR mice were obtained from three difference sources. Korl:ICR mice were kindly provided by the National Institute of Food and Drug Safety Evaluation (NIFDS). The other two groups of ICR mice were purchased from different vendors located in the United States (A:ICR) and Japan (B:ICR). All ICR mice that received MLDS exhibited overt diabetic symptoms throughout the study, and the incidence and development of diabetes mellitus were similar among the three ICR groups. The diabetic mice exhibited hyperglycemia, loss of body weight gain, decreased plasma insulin levels, impaired glucose tolerance, decreased number of insulin-positive cells, and decreased size of β-cells in the pancreas. The diabetes symptoms increased as the blood glucose level increased in the three ICR groups. In particular, the level of blood glucose in the STZ-treated group was higher in Korl:ICR and A:ICR mice than in B:ICR mice. The plasma insulin levels, glucose tolerance, blood chemistry, and morphological appearance of the pancreas were very similar in the ICR groups obtained from the three different sources. In conclusion, our results suggest that Korl:ICR, A:ICR, and B:ICR mice from different sources had similar overall responses to multiple low-dose STZ to induce diabetes mellitus.

Inhibitory Effect of Carnosol on Phthalic Anhydride-Induced Atopic Dermatitis via Inhibition of STAT3

Carnosol is a phenolic antioxidant present in rosemary (Rosmarinus officinalis). It is known for anti-inflammatory effects, analgesic activity and anti-cancer effects. However, no study has been dedicated yet to its effect on atopic dermatitis (AD). Here, we show that carnosol effectively inhibited LPS-induced nitric oxide (NO) generation and expression of inflammatory marker proteins (iNOS and COX-2) in RAW 264.7 cells. In addition, carnosol effectively inhibits the phosphorylation of STAT3 and DNA binding activity in RAW 264.7 cells. Pull down assay and docking model analysis showed that carnosol directly binds to the DNA binding domain (DBD) of STAT3. We next examined the anti-atopic activity of carnosol (0.05 μg/cm²) using 5% Phthalic anhydride (PA)-induced AD model in HR1 mice. Carnosol treatment significantly reduced 5% PA-induced AD like skin inflammation in skin tissues compared with control mice. Moreover, carnosol treatment inhibits the expression of iNOS and COX-2 in skin tissue. In addition, the levels of TNF-α, IL-1β, and Immunoglobulin-E in blood serum was significantly decreased in carnosol treated mice compared with those of 5% PA treated group. Furthermore, the activation of STAT3 in skin tissue was decreased in carnosol treated mice compared with control mice. In conclusion, these findings suggest that carnosol exhibited a potential anti-AD activity by inhibiting pro-inflammatory mediators through suppression of STAT3 activation via direct binding to DBD of STAT3.

Modulation of SOD1 Subcellular Localization by Transfection with Wild- or Mutant-type SOD1 in Primary Neuron and Astrocyte Cultures from ALS Mice

Amyotrophic lateral sclerosis (ALS) is a fatal neurological disorder characterized by selective degeneration of motor neurons. Mutant superoxide dismutase 1 (SOD1) is often found as aggregates in the cytoplasm in motor neurons of various mouse models and familial ALS patients. The interplay between motor neurons and astrocytes is crucial for disease outcome, but the mechanisms underlying this phenomenon remain unknown. In this study, we investigated whether transient transfection with wild-type and mutant-type SOD1 may lead to amplification of mutant SOD1-mediated toxicity in cortical neurons and astrocytes derived from wild-type and mutant-type (human G93A-SOD1) mice. In transgenic mice expressing either wild- or mutant-type SOD1, we found that green fluorescent protein (GFP)-wtSOD1 was present in the cytoplasm and nuclei of wild-type cortical neurons and astrocytes, whereas GFP-mutant SOD1 was mainly cytoplasmic in wild- and mutant-type cortical neurons and astrocytes. These findings indicate that intracellular propagation of misfolding of GFP-wt or mtSOD1 are possible mediators of toxic processes involved in initiating mislocalization and aggregation. Here, we provide evidence that cytoplasmic aggregates induce apoptosis in G93A-SOD1 mouse cortical neurons and astrocytes and that the toxicity of mutant SOD1 in astrocytes is similar to the pathological effects of ALS on neurons in vitro. Collectively, our results indicate that mtSOD1 probably interacts with wtSOD1 via an unknown mechanism to produce augmented toxicity and may influence aggregate formation and apoptosis.

Effect of ECQ on Iodoacetamide-Induced Chronic Gastritis in Rats

This study investigated effect of extract containing quercetin-3-O-beta-D-glucuronopyranoside from Rumex Aquaticus Herba (ECQ) against chronic gastritis in rats. To produce chronic gastritis, the animals received a daily intra-gastric administration of 0.1 ml of 0.15% iodoacetamide (IA) solution for 7 days. Daily exposure of the gastric mucosa to IA induced both gastric lesions and significant reductions of body weight and food and water intake. These reductions recovered with treatment with ECQ for 7 days. ECQ significantly inhibited the elevation of the malondialdehyde levels and myeloperoxidase activity, which were used as indices of lipid peroxidation and neutrophil infiltration. ECQ recovered the level of glutathione, activity of superoxide dismutase (SOD), and expression of SOD-2. The increased levels of total NO concentration and iNOS expression in the IA-induced chronic gastritis were significantly reduced by treatment with ECQ. These results suggest that the ECQ has a therapeutic effect on chronic gastritis in rats by inhibitory actions on neutrophil infiltration, lipid peroxidation and various steps of reactive oxygen species (ROS) generation.

Protective Effect of Fibroin BF-7 on Neuronal Cell Death in Alzheimer Model using Amyloid beta Peptide / 대한해부학회지

Factors such as senescence,stress and neurodegenerative diseases,including Alzheimer's disease, contribute to the impairment of organs,especially the brain.They also negatively affect normal brain functions such as memory and cognition.In this study,the neuroprotective role of the natural product BF-7 was examined against A beta - induced neurotoxicity in SK-N-SH human neuronal cells.BF-7 significantly attenuated A beta-induced apoptosis as measured by intracellular calcium levels,accumulation of reactive oxygen species,mitochondrial dysfunction,and caspase activity.These results strongly indicate that BF-7 plays an effective and positive role in the improvement of brain functions,including learning and memory,in our model system for Alzheimer's disease.Thus,BF-7 might be useful for developing strategies to protect the nervous system and improve brain function.

Study on the Mitochondrial Dysfunction by p53 Regulation in Ceramide-induced Neuronal Cell Death / 체질인류학회지

Ceramide induces cell death in a dose- and time-dependent manner in neuroblastoma SK-N-SH cells. To investigate the mechanism of SK-N-SH cell death by C2-ceramide, morphological features and Hoechst 33258 staining were analyzed. In these morphlogic study the cell death by ceramide showed typical apoptotic features, nuclear condensation, fragmentation, and membrane blebbing. Ceramide-induced apoptosis was accompanied by nuclear accumulation of p53. Inhibition of p53 expression with p53 antisense oligonucleotides inhibited apoptosis evoked by ceramide. Also, ceramide induced mitochondrial event, collapse of mitochondrial membrane potential (delta psi m) and interestingly, inhibition of p53 attenuated collapse of mitochondrial membrane potential, suggests that ceramide induces mitochondrial dysfunction through upregulation of p53 expression. These results suggest that ceramide-induced apoptosis is dependent upon increase in cellular p53 levels which play a critical role in the regulation of apoptotic cell death and p53 modulates mitochondrial function such as mitochondrial membrane potential level.

Protective Effect of Green Tea Extract on Neuronal Cell Death in Alzheimer Model using beta-amyloid Peptide / 대한해부학회지

In the present study, we determined whether green tea extract, EGCG protected against beta-amyloid induced neurotoxicity and learning impairment in vitro and in vivo models. Incubation of SK-N-SH cells with Abeta induced activation of caspase-3, mitochondrial dysfunction such as collapse of mitochondrial membrane potential (MMP) and release of cytosolic cytochrome c. Interestingly, pre-treatment of EGCG reduced significantly activation of caspase-3 and increase of mitochondrial damage such as the breakdown of MMP and release of cytochrome c, eventually attenuated the cell death induced by Abeta. These results show that EGCG inhibited caspase activity and blocked mitochondrial damage. For in vivo experiment, ICR mice received vehicle or vehicle plus EGCG (10 mg/kg) i.p. for 3 days. Before 2 days of treatment, 5 microliter of PBS containing 8 nmol of Abeta1-42 were injected into the lateral ventricle. On the 14th day of treatment, animals were applied to passive avoidance test, and after behavial test, animals were sacrificed. Then, morphological techniques were used to determine the extent of neuronal degeneration in the hippocampus. Abeta, but not PBS, injections into hippocampus led to neuronal loss and evidence of widespread apoptosis. EGCG treated animals had significant reductions in the amount of neuronal degeneration, and TUNEL positive cells compared with Abeta alone treated animals. These data suggest that EGCG at therapeutically relevant concentrations, might protect against neuronal degeneration induced by Abeta.

Risk factors of acute hepatic failure associated with transcatheter arterial chemoembolization for hepatocellular carcinoma / 대한내과학회지

BACKGROUND: Transcatheter Arterial Chemoembolization (TACE) has been the most widely used treatment for advanced hepatocellular carcinoma (HCC) in Korea. However a number of complications associated with TACE have been reported in many studies. Acute hepatic failure is one of the most serious complications of TACE, because of its grave prognosis. The aim of this study was to investigate the risk factors associated with acute hepatic failure after TACE. METHODS: A total of 263 TACE procedures performed in 163 patients with HCC were included in this study. We reviewed retrospectively the complications that occurred after TACE and analysed the risk factors associated with acute hepatic failure after TACE. RESULTS: Complications included post-embolization syndrome (187 cases), temporary hepatic insufficiency (90 cases), acute hepatic failure (13 cases), hepatic arterial injury (9 cases), intrahepatic biloma (4 cases), liver infarction (2 cases), liver abscess (2 cases), tumor rupture (1 cases), gastrointestinal bleeding (14 cases), septicemia (3 cases), gall bladder infarction (2 cases), thrombocytopenia (2 cases), gastric perforation (1 cases), pneumonia (1 cases), urticaria (1 cases), sensorineural hearing loss (1 cases), femoral artery aneurysm (1 cases). According to univariate analysis, risk factors associated with acute hapatic failure after TACE were serum bilirubin and albumin, prothrombin time, dose of adriamycin, pre-TACE Child-Pugh class, tumor size, diffuse tumor type, portal vein thrombosis and TNM stage. Multivariate analysis revealed that serum bilirubin {odd ratio=3.86 (95% CI: 1.59-9.32)}, and diffuse tumor type {odd ratio=5.29 (95% CI: 1.46-23.86)} were statistically significant risk factors. CONCLUSIONS: It is recommended that above mentioned risk factors should be considered carefully before TACE to prevent the occurrence of acute hepatic failure after TACE in HCC patients.

BF-7 Improved Memory Function and Protected Neuron from Oxidative Stress / 체질인류학회지

Endogenously or exogenously generated oxidative stress impair organs, especially brain. Also, the oxidative stress appears to be a negative factor on normal brain function, like memory and cognition. Our result showed that BF-7, extracted from Bombyx mori, effectively diminished oxidative stress, leading to the protection of neuron from reactive oxygen species donated by FeSO4 . Clinical experiments showed that BF-7 significantly improved memory and cognitive functions of normal adults in a dose-dependent manner. Thus, our results suggest that BF-7 play a role in the improvement of brain functions by removing oxidative stress, and provide therapeutic potential role of BF-7 to protect nervous system from oxidative damage.

Down-regulated Reactive Oxygen Species by Heat Shock Protein 90 in 3-Hydroxykynurenine-induced SKN-SH Cell Death / 체질인류학회지

In this present study, we show that 3HK-induced reactive oxygen species (ROS) accumulation and caspase activation lead to apoptotic cell death. Pretreatment with N-acetylcysteine (NAC), an effective antioxidant, significantly attenuated 3HK-induced apoptosis by way of a reduction of ROS accumulation and caspase activity. SKN-SN cells were protected from 3HK-induced cytotoxicity by heat shock protein (HSP). HSP90 effectively attenuated 3HK-mediated ROS accumulation and apoptosis. In addition, the protective effect of HSP90 was abolished by pretreatment with HSP90 anti-sense oligonucleotide, but not when pretreated with anti-senses for other HSPs. These results suggest that HSP90 protects SKN-SH cells from 3HK-induced cytotoxicity by reducing ROS levels and caspase activity.

Studies on Signal Transduction Mechanism of Alcohol-induced Neuronal Cell Death and Protective Effect / 체질인류학회지

Excessive use of alcohol is a serious problem in our society and induces various, severe alcohol related diseases. The cytotoxicities of ethanol are still largely unknown. We studied the molecular mechanisms of EtOH-induced SK-N-SH neuronal cell death and protective effects of baicalein and gramineus against EtOH-induced cytotoxicities. In our results, the cell death by EtOH showed morphologic features of apoptosis like as membrane blebbing, nuclear condensation and fragmentation. Furthermore, pretreated baicalein attenuated EtOH-induced neuronal cell death effectively. EtOH increased expression levels of p53 and both p53 antisense oligonucleotide and Pifithrin protected the cell death against EtOH. Also, EtOH induced mitochondrial event, collapse of mitochondrial membrane potential ( delta psi m ) and caspase cascade as a downstream of mitochondria. Interestingly, baicalein decreased expression levels of p53 and inhibited collapse of mitochondrial membrane potential. These results suggest that baicalein reduces mitochondrial dysfunction induced by EtOH through down-regulation of p53 expression levels. Also, baicalein attenuated activation of caspase, which was triggered by mitochondrial malfunction. But gramineus didn't have any protective effect. These results imply that baicalein significantly protects EtOH-induced neuronal cell death through regulating p53, mitochondrial dysfunction and caspase activation.

Studies on Signal Transduction Mechanism of Alcohol-induced Neuronal Cell Death and Protective Effect / 체질인류학회지

Excessive use of alcohol is a serious problem in our society and induces various, severe alcohol related diseases. The cytotoxicities of ethanol are still largely unknown. We studied the molecular mechanisms of EtOH-induced SK-N-SH neuronal cell death and protective effects of baicalein and gramineus against EtOH-induced cytotoxicities. In our results, the cell death by EtOH showed morphologic features of apoptosis like as membrane blebbing, nuclear condensation and fragmentation. Furthermore, pretreated baicalein attenuated EtOH-induced neuronal cell death effectively. EtOH increased expression levels of p53 and both p53 antisense oligonucleotide and Pifithrin protected the cell death against EtOH. Also, EtOH induced mitochondrial event, collapse of mitochondrial membrane potential ( delta psi m ) and caspase cascade as a downstream of mitochondria. Interestingly, baicalein decreased expression levels of p53 and inhibited collapse of mitochondrial membrane potential. These results suggest that baicalein reduces mitochondrial dysfunction induced by EtOH through down-regulation of p53 expression levels. Also, baicalein attenuated activation of caspase, which was triggered by mitochondrial malfunction. But gramineus didn't have any protective effect. These results imply that baicalein significantly protects EtOH-induced neuronal cell death through regulating p53, mitochondrial dysfunction and caspase activation.

The Activation of ERK1/2 Via Tyrosine Kinase Pathway Attenuates TRAIL-induced Apoptosis in HeLa cell / 체질인류학회지

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) serves as an extracellular signal triggering apoptosis in tumor cells. To characterize the molecular events involved in TRAIL-induced apoptotic signaling, we investigated the role of extracellular signal-regulated kinase 1/2(ERK1/2) in the apoptosis using HeLa cells. Here we show that TRAIL pronounced ERK1/2 activation through a tyrosine kinase-dependent mechanism, subsequently elevated anti-apoptotic Bcl-2 protein levels. Pretreatment with Genistein, an inhibitor of tyrosine kinase, significantly attenuated ERK1/2 activation and enhanced cell death. Moreover, inhibition of ERK1/2 with PD98059 promoted apoptotic cell death through the down-regulation of ERK1/2 activity and Bcl-2 protein levels. Taken together, our results suggest that the activation of ERK1/2 via tyrosine kinase pathway plays a protective role as the mechanism of cellular defense through the up-regulation of Bcl-2 protein levels in TRAIL-induced apoptosis.

Attenuated Ceramide-induced Neuronal Apoptosis by Acanthopanax senticous / 체질인류학회지

Both Acanthopanax senticosus and Acorus gramineus Soland are typical Oriental herbs. They have been used as a tonic, anti-rheumatic, anti-inflammatory, anti-stress, anti-cancer agent. But, it is still unclear how they effectively regulate their various biological properties. Ceramide is emerging as a second messenger of apoptotic cell death and there is increasing evidence that ceramide is involved in neurodegenerative disease and the process of senescence. The present study investigated the different effects of A. senticosus and A. gramineus on ceramide-induced apoptosis in human neuroblastoma SK-N-SH cells. We showed that ceramide induced apoptosis through the mediation of reactive oxygen species(ROS) production and A. senticosus, as an effective antioxidant, significantly inhibited the increase of ROS generation, thereby preventing apoptosis. Furthermore, an increase of caspase activity (apoptosis executors) resulted from ceramide reduced by A. senticosus. But A. gramineus had almost no protective effects. These results implicate that ROS play on important roles in ceramide-induced apoptosis, also A. senticosus protects effectively via inhibition of ROS generation by ceramide through selective pathway.

Protective Effect of Magnolol Against Ceramide-induced Apoptosis in SK-N-SH cells / 체질인류학회지

Magnolol, isolated from the stem bark of Magnolia officnalis, is typical Oriental herbs. It has been known to have many biological activities such as anti-platelet aggregation, hydroxyl radical scavenging, Ca2+ -channel blocking, a tonic, anti-rheumatic, anti-stress, anti-inflammatory, anti-cancer action and ischemic heart disease. But, it is still unclear how they effectively regulate their various biological properties. Ceramide is emerging as a second messenger of apoptotic cell death and there is increasing evidence that ceramide is involved in neurodegenerative disease and the process of senescence. The present study investigated the effect of Magnolol on ceramide-induced apoptosis in human neuroblastoma SK-N-SH cells. We showed that ceramide induced apoptosis through the mediation of reactive oxygen species (ROS) production and Magnolol, as an effective antioxidant, significantly inhibited the increase of ROS generation, thereby preventing apoptosis. Furthermore, an increase of caspase activity (apoptosis executors) resulted from ceramide reduced by Magnolol. These results implicate that ROS play on important roles in ceramide-induced apoptosis, also Magnolol protects via effectively inhibition of ROS generation by ceramide through selective pathway.

Uterine Arterial Embolization for the Treatment of Leiomyomas Accompanying with Adenomyosis / 대한불임학회지

OBJECTIVE: The purpose of this study was to make a guideline of uterine artery embolization for the treatment of uterine leiomyomas accompanying with adenomyosis in Korea. MATERIALS AND METHODS: We performed the retrospective study for 37 women who had uterine leiomyomas accompanying with adenomyosis. Bilateral uterine artery embolization was performed in 37 patients (age range 25-65) during 17 months with pain, hypermenorrhea, urinary frequency etc due to leiomyomas. Ultrasound imaging was performed before the procedure and at mean 6.9 months after the procedure. RESULTS: All procedures were technically successful. Mean clinical follow-up was 12.8 months. Minor complication occurred in 82% patients after the procedure. After imaging follow-up (mean, 6.9 months postprocedure), median uterine volume decreased 34.4%, and dominant myoma volume decreased 86%. There was no statistical difference in uterine volume reduction and dominant myoma size reduction whether occluding agents was polyvinyl alcohol, polyvinyl alcohol plus gelfoam, and gelfoam, and whether ultrasound measured Resistance Index value before the procedure was low or high. CONCLUSION: Primary candidates for uterine artery embolization include those with symptomatic uterine leiomyomas who no longer desire fertility but wish to avoid surgery or are poor surgical risks. To our study, uterine volume reduction and dominant myoma size reduction in patients who had adenomyosis were similar to previous other studies in patients who had not adenomyosis. Therefore adenomyosis should not be considered as a contraindication for uterine artery embolization. Because there is little data about subsequent reproductive potential after this procedure, it should not be routinely advocated for infertile women. Further investigation is warranted for occluding agents and Resistance Index.

Aldosterone-Producing Adenoma Diagnosed by Selective Adrenal Venous Catheterization / 대한내분비학회지

Primary aldosteronism, not a common cause of high blood pressure, is a syndrome which results from excessively secreted aldosterone from adrenal gland and it accounts for 0.05-2.2% of unselected hypertension. In this case the lesion was not visualized on routine abdominal computed tomographic scan due to its small size. Therefore the selective adrenal venous catherterization & venous sampling was done. As there is some difficulty of sampling from Rt. adrenal vein, the method of measuring aldosterone vs. cortisol ratio of Lt. adrenal vein and inferior vena cava was used to localize the aldosterone-producing adenoma. Clinical symptoms normalized and laboratory data returned to normal range after the surgical adrenalectomy.

Percutaneous Transluminal Coronary Angioplasty for Coronary Artery Stenosis in an Adult Kawasaki Disease with Coronary Aneurysm : A Case Report and Review

We experience coronary artery aneurysm and coronary artery stenosis in an adult as complications of Kawasaki disease. The patient suffered from ischemic heart disease due to coronary artery aneurysm and stenosis, We carried out PTCA and stenting at stenotic coronary artery successfully. A brief review of related literature was made.

Nonsurgical Treatment of Femoral Pseudoaneurysm Complicating Cardiac Catheterization

BACKGROUND: With the recent development in arterial reconstructive procedure such as percutaneous transluminal coronary angioplasty or atherectomy, the incidence of vascular complications involving femoral artery is increasing due to greater use of larger percutaneous instruments(including arterial sheath) and periprocedural anticoagulant therapy. Femoral pseudoaneurysm requires rapid diagnosis and management to prevent limb ischemia, worsening of the arterial injury or repair of the arterial defect. Recently, accurate diagnosis of these injuries can be made nonivasively with duplex sonography and Doppler color flow imaging, and nonsurgical treatment may be possible by using external compression guided by ultrasound even in patients requiring prolonged anticoagulant therapy. METHOD: Three patients, one undergoing coronary angiography and two undergoing percutaneous transluminal coronary angioplasty, developed expansile groin masses at the vascular access sites diagnosed as femoral artery pseudoaneurysm s by Doppler ultrasound. All patients were hypertensives, taking aspirin and two patients who underwent PTCA received intravenous heparin after procedure. After diagnosis of femoral pseudoaneurysm, all patients underwent mechanical(C-clamp) external compression guided by ultrasound for 3 hours. RESULT: Follow up color flow scans were obtained after 24 hours and in one patients, blood flow in the tract was eliminated but persistent blood flow was observed in two patients who underwent PTCA. Before closure of pseudoaneurysm, one patient needed another 6 hours of ultrasound guided compression and the other needed more 12 hours. All patients were discharged without complication or recurrence of pseudoaneurysm. CONCLUSION: These cases suggest that nonsurgical closure of femoral pseudoaneurysms is feasible even in patients requiring prolonged antiplatelet and anticoagulant therapy.