Inflammatory Myofibroblastic Tumor Misdiagnosed as Intrahepatic Cholangiocarcinoma / 대한소화기학회지

An inflammatory myofibroblastic tumor (IMT) is a rare tumor that is currently classified as an intermediate cancer according to the World Health Organization classification system. The pathophysiology of its occurrence is still unknown. Imaging tests, such as CT or MRI, can be helpful in diagnosis, but the final diagnosis is confirmed by a pathological examination through a biopsy and immunohistochemistry stain. The patient, in this case, presented an asymptomatic intrahepatic mass discovered incidentally on an imaging examination. Initially, intrahepatic cholangiocarcinoma was suspected, but she was finally diagnosed with IMT through a histological examination after a liver resection.

Catheter ablation of atrial fibrillation in Korea: results from the Korean Heart Rhythm Society Ablation Registry for Atrial Fibrillation (KARA)

Background@#This study aims to investigate the current status of AF (atrial fibrillation) catheter ablation in Korea. @*Methods@#The patients who underwent AF catheter ablation from September 2017 to December 2019 were pro‑ spectively enrolled from 37 arrhythmia centers. Demographic data, procedural characteristics, the extent of catheter ablation, acute success of the ablation lesion set, rate and independent risk factor for recurrence of AF were analyzed. @*Results@#A total of 2402 AF patients [paroxysmal AF (PAF) 45.7%, persistent AF (PeAF) 43.1% and redo AF 11.2%] were included. Pulmonary vein isolation (PVI) was performed in 2378 patients (99%) and acute success rate was 97.9%.Additional non-PV ablation (NPVA) were performed in 1648 patients (68.6%). Post-procedural complication rate was 2.2%. One-year AF-free survival rate was 78.6% and the PeAF patients showed poorer survival rate than the ones with other types (PeAF 72.4%, PAF 84.2%, redo AF 80.0%). Additional NPVA did not influence the recurrence of AF in the PAF patients (PVI 17.0% vs. NPVA 14.6%, P value 0.302). However, it showed lower AF recurrence rate in the PeAF patients (PVI 34.9% vs. NPVA 24.4%, P value 0.001). Valvular heart disease, left atrial diameter, PeAF, PVI alone, need of NPVA for terminating AF, and failed ablation were independent predictors of AF recurrence. @*Conclusions@#Additional NPVA was associated better rhythm outcome in the patients with PeAF, not in the ones with PAF. The independent risk factors for AF recurrence in Korean population were similar to previous studies. Further research is needed to discover optimal AF ablation strategy.

Design of Korean Noninvasive Risk Evaluation Study for Sudden Cardiac Death from Infarction or Heart Failure: Myocardial infarction study of K-REDEFINE registry

BACKGROUND AND OBJECTIVES: Despite significant advances in the treatment of acute myocardial infarction (MI), the prevention of sudden cardiac death (SCD), the most common mode of death in patients with MI, remains challenging. Furthermore, previous Korean MI registries did not address the issue of post-MI SCD. Additional risk stratifiers of post-MI SCD are still required to compensate for the limitation of using left ventricular ejection fraction to predict lethal arrhythmic events. SUBJECTS AND METHODS: We designed the first Korean prospective nationwide multicenter registry primarily focused on SCD; the Korean noninvasive Risk Evaluation study for sudden cardiac DEath From INfarction or heart failurE (K-REDEFINE). The registry consists of 2 groups of patients presenting with (1) acute MI or (2) acute heart failure (HF) at 25 tertiary referral cardiovascular centers. The primary endpoint of the MI group study of K-REDEFINE registry is the incidence and risk factors of post-MI SCD. In particular, the association between the risk of SCD and non-invasive Holter-based electrocardiogram (ECG) variables will be evaluated, such as T-wave alternans (marker of repolarization heterogeneity) and heart rate turbulence/variability (a marker of autonomic function). Other secondary study outcomes include atrioventricular arrhythmias, HF-related admission, repeated myocardial ischemic events, stroke, and overall deaths. CONCLUSION AND PERSPECTIVE: The K-REDEFINE registry will provide new prospects for the better management of MI patients with high risk of SCD by clarifying the burden and predictors of SCD and the clinical utility of various non-invasive ambulatory ECG-based variables in risk stratification for SCD in this patient population.

Design of Korean Noninvasive Risk Evaluation Study for Sudden Cardiac Death from Infarction or Heart Failure: Heart failure study of K-REDEFINE registry

BACKGROUND AND OBJECTIVES: Sudden cardiac death (SCD) is one of the most common causes of death in patients with heart failure (HF). However, there are no available data on SCD in previous Korean HF registries. Additionally, although widely used, the utility of left ventricular (LV) ejection fraction (EF) in risk stratification for SCD is limited. SUBJECTS AND METHODS: The Korean non-invasive Risk Evaluation study for sudden cardiac DEath From INfarction or heart failurE (KREDEFINE) is the first Korean prospective, nationwide multicenter registry, primarily focused on SCD. The registry consists of 2 groups of patients presenting with (1) acute HF or (2) acute myocardial infarction (MI) at 25 tertiary referral cardiovascular centers. Using the HF-group data of the K-REDEFINE registry, the incidence and risk factors of SCD in patients with HF will be assessed. In particular, the efficacy of Holter-based ECG variables, such as T-wave alternans (marker of repolarization heterogeneity) and heart rate turbulence/ variability (maker of autonomic function), in risk stratification for SCD will be evaluated. Other cardiovascular outcomes will also be analyzed, including atrioventricular arrhythmias, HF-related admission, stroke, and overall deaths. CONCLUSION AND PERSPECTIVE: The K-REDEFINE registry will pave the way for better management of patients with HF at high risk of SCD by elucidating the burden and risk factors of SCD and the clinical utility of various non-invasive ambulatory ECG-based parameters in risk stratification for SCD in this patient population.

Effects of Angiotensin-II Receptor Blocker on Inhibition of Thrombogenicity in a Canine Atrial Fibrillation Model

BACKGROUND AND OBJECTIVES: Angiotensin-II receptor blockers (ARBs) are known to reduce the development of atrial fibrillation (AF) through reverse-remodeling. However, the effect of ARBs on thrombogenicity in AF remains unknown. MATERIALS AND METHODS: Twelve dogs were assigned to control (n=4), ARB (candesartan cilexitil 10 mg/kg/day p.o., 12 weeks; n=4), or sham (n=4) groups. Sustained AF was induced by rapid atrial pacing. Both arterial and venous serum levels of tissue inhibitor of matrix metalloproteinase-1, von Willebrand factor, P-selectin, and vascular cell adhesion molecule-1 (VCAM-1) were measured at baseline and during AF (0, 4, and 12 weeks) with enzyme-linked immunosorbent assay. Biopsies from both atria including the appendages were performed to semi-quantitatively assess endocardial and myocardial fibrosis after 12 weeks. RESULTS: The serum levels of bio-markers were not significantly different at baseline or during AF between the control and the candesartan groups. The levels were not significantly different over time, but there was a trend toward a decrease in arterial VCAM-1 from 4 to 12 weeks in the candesartan group compared to the control group. The grades of endocardial fibrosis after 12 weeks but not those of myocardial fibrosis were slightly reduced in the candesartan group compared to the control group. CONCLUSION: This study did not show that the ARB candesartan significantly reverses thrombogenicity or fibrosis during AF. Future studies using a larger number of subjects are warranted to determine the therapeutic effect of renin-angiotensin-aldosterone system blockade on prothrombogenic processes in AF.

Neonatal invasive Streptococcus gallolyticus subsp. pasteurianus infection with delayed central nervous system complications / 소아과

Group D streptococci are known to cause newborn septicemia and meningitis, but the Streptococcus bovis group strains rarely cause serious neonatal infections in Korea. Central nervous system (CNS) complications of neonatal S. bovis group infection have rarely been reported. In adults, S. bovis group strains cause bacteremia and endocarditis, and are associated with gastrointestinal malignancy. However, only a few studies have reported meningitis and septicemia in infants. Here, we describe a case of bacteremia and meningitis due to Streptococcus gallolyticus subsp. pasteurianus with a delayed CNS complication in an infant. A 28-day-old male infant was admitted to the hospital with a 1-day history of fever. Cultures of blood, cerebrospinal fluid, and urine showed the presence of S. bovis group strain-S. gallolyticus subsp. pasteurianus. He was discharged after 21 days of intravenous ampicillin and cefotaxime administration. Two weeks later, he was readmitted with a fever and short episodes of tonic-clonic movements. Brain magnetic resonance imaging showed marked bilateral frontal subdural effusion. He was discharged after 31 days of antibiotic therapy, and no neurological sequelae were observed at the 9-month follow-up. In conclusion, we present a rare case of neonatal S. gallolyticus subsp. pasteurianus infection causing urinary tract infection, septicemia, meningitis, and delayed CNS complications. This case emphasizes the need for physicians to be aware of S. bovis infection in infants.

Swallowing-Induced Atrial Tachyarrhythmias Successfully Ablated at the Left Posterior Interatrial Septum in Patient with Wolff-Parkinson-White Syndrome

We reported a case of a 55-year-old patient who presented with palpitation after swallowing. Initial surface electrocardiogram revealed ventricular preexcitation utilizing a left lateral bypass tract. The orthodromic atrioventricular reentrant tachycardia (AVRT) was induced during electrophysiologic studies. After successful ablation of the AVRT utilizing a left lateral free wall bypass tract, 2 different atrial tachycardias (ATs) were induced under isoproterenol infusion. When the patient swallowed saliva or drank water, 2 consecutive beats of atrial premature complexes (APCs) preceded another non-sustained AT repeatedly, which was coincident with the patient's symptom. The preceding APC couplet had the same activation sequence with one induced AT, and the subsequent non-sustained AT had the same activation sequence with the other induced AT, respectively. We first targeted the preceding 2 consecutive APCs at the left posterior interatrial septum. The following non-sustained AT was also eliminated following ablation of the APCs. After ablation, the patient remained free from the swallowing-induced atrial tachyarrhythmias during the one year follow-up.

Prognosis after Implantation of Cardioverter-Defibrillators in Korean Patients with Brugada Syndrome

PURPOSE: Our study aims to analyze prognosis after implantable cardioverter-defibrillator (ICD) implantation in Korean patients with Brugada syndrome (BrS). MATERIALS AND METHODS: This was a retrospective study of BrS patients implanted with an ICD at one of four centers in Korea between January 1998 and April 2012. Sixty-nine patients (68 males, 1 female) were implanted with an ICD based on aborted cardiac arrest (n=38, 55%), history of syncope (n=17, 25%), or induced ven tricular tachyarrhythmia on electrophysiologic study in asymptomatic patients (n=14, 20%). A family history of sudden cardiac death and a spontaneous type 1 electrocardiography (ECG) were noted in 13 patients (19%) and 44 patients (64%), respectively. RESULTS: During a mean follow-up of 59+/-46 months, 4.6+/-5.5 appropri ate shocks were delivered in 19 patients (28%). Fourteen patients (20%) experienced 5.2+/-8.0 inappropriate shocks caused by supraventricular arrhythmia, lead failure, or abnormal sensing. Six patients were admitted for cardiac causes during follow-up, but no cardiac deaths occurred. An episode of aborted cardiac arrest was a significant predictor of appropriate shock, and the composite of cardiac events in the Cox pro portional hazard model [hazard ratio (95% confidence interval) was 11.34 (1.31-97.94) and 4.78 (1.41-16.22), respectively]. However, a spontaneous type 1 ECG was not a predictor of cardiac events. CONCLUSION: Appropriate shock (28%) and inappropriate shock (20%) were noted during a mean follow-up of 59+/-46 months in Korean BrS patients implanted with an ICD. An episode of aborted cardiac ar rest was the most powerful predictor of cardiac events.

Ten years of experience in the prevention of mother-to-child human immunodeficiency virus transmission in a university teaching hospital / 소아과

PURPOSE: Administration of antiretroviral drugs to mothers and infants significantly decreases mother-to-child human immunodeficiency virus (HIV) transmission; cesarean sections and discouraging breastfeeding further decreases this risk. The present study confirmed the HIV status of babies born to mothers infected with HIV and describes the characteristics of babies and mothers who received preventive treatment. METHODS: This study retrospectively analyzed medical records of nine infants and their mothers positive for HIV who gave birth at Korea University Ansan Hospital, between June 1, 2003, and May 31, 2013. Maternal parameters, including HIV diagnosis date, CD4+ count, and HIV ribonucleic acid (RNA) copy number, were analyzed. Infant growth and development, HIV RNA copy number, and HIV antigen/antibody test results were analyzed. RESULTS: Eight HIV-positive mothers delivered nine babies; all the infants received antiretroviral therapy. Three (37.5%) and five mothers (62.5%) were administered single- and multidrug therapy, respectively. Intravenous zidovudine was administered to four infants (50%) at birth. Breastfeeding was discouraged for all the infants. All the infants were negative for HIV, although two were lost to follow-up. Third trimester maternal viral copy numbers were less than 1,000 copies/mL with a median CD4+ count of 325/microL (92-729/microL). Among the nine infants, two were preterm (22.2%) and three had low birth weights (33.3%). CONCLUSION: This study concludes that prophylactic antiretroviral therapy, scheduled cesarean section, and prohibition of breastfeeding considerably decrease mother-to-child HIV transmission. Because the number of infants infected via mother-to-child transmission may be increasing, studies in additional regions using more variables are necessary.

Inadvertently Developed Ventricular Fibrillation during Electrophysiologic Study and Catheter Ablation: Incidence, Cause, and Prognosis

BACKGROUND AND OBJECTIVES: Ventricular fibrillation (VF) can inadvertently occur during electrophysiologic study (EPS) or catheter ablation. We investigated the incidence, cause, and progress of inadvertently developed VF during EPS and catheter ablation. SUBJECTS AND METHODS: We reviewed patients who had developed inadvertent VF during EPS or catheter ablation. Patients who developed VF during programmed ventricular stimulation to induce ventricular tachycardia or VF were excluded. RESULTS: Inadvertent VF developed in 11 patients (46.7+/-9.3 years old) among 2624 patients (0.42%); during catheter ablation for atrial fibrillation (AF) in nine patients, frequent ventricular premature beats (VPBs) in one, and Wolff-Parkinson-White (WPW) syndrome were observed in one. VF was induced after internal cardioversion in six AF patients due to incorrect R-wave synchronization of a direct current shock. Two AF patients showed spontaneous VF induction during isoproterenol infusion while looking for AF triggering foci. The remaining AF patient developed VF after rapid atrial pacing to induce AF, but the catheter was accidentally moved to the right ventricular (RV) apex. A patient with VPB ablation spontaneously developed VF during isoproterenol infusion. The focus of VPB was in the RV outflow tract and successfully ablated. A patient with WPW syndrome developed VF after rapid RV pacing with a cycle length of 240 ms. Single high energy (biphasic 150-200 J) external defibrillation was successful in all patients, except in two, who spontaneously terminated VF. The procedure was uneventfully completed in all patients. At a mean follow-up period of 17.4+/-15.5 months, no patient presented with ventricular arrhythmia. CONCLUSION: Although rare, inadvertent VF can develop during EPS or catheter ablation. Special caution is required to avoid incidental VF during internal cardioversion, especially under isoproterenol infusion.

Electrophysiological Characteristics Related to Outcome after Catheter Ablation of Idiopathic Ventricular Arrhythmia Originating from the Papillary Muscle in the Left Ventricle

BACKGROUND AND OBJECTIVES: The electrophysiological properties associated with favorable outcome of radiofrequency catheter ablation (RFCA) for idiopathic ventricular arrhythmia (VA) originating from the papillary muscle (PM) remain unclear. The purpose of this study was to investigate the relationships of electrophysiological characteristics and predictors with the outcome of RFCA in patients with VAs originating from PM in the left ventricle (LV). SUBJECTS AND METHODS: Twelve (4.2%) of 284 consecutive patients with idiopathic VAs originating from LV PM were assessed. The electrophysiological data were compared between the patients in the successful group and patients in the recurrence group after RFCA. RESULTS: In 12 patients with PM VAs, non-sustained ventricular tachycardias (VTs, n=6), sustained VTs (n=4) and premature ventricular complexes (n=2) were identified as the presenting arrhythmias. Seven of eight patients showing high-amplitude discrete potentials at the ablation site had a successful outcome (85.7%), while the remaining four patients who showed low-amplitude fractionated potentials at the ablation site experienced VA recurrence. The mean duration from onset to peak downstroke (Deltat) on the unipolar electrogram was significantly longer in the successful group than in the recurrence group (58+/-8 ms vs. 37+/-9 ms, p=0.04). A slow downstroke >50 ms of the initial Q wave on the unipolar electrogram at ablation sites was also significantly associated with successful outcome (85.7% vs. 25.0%, p=0.03). CONCLUSION: In PM VAs, the high-amplitude discrete potentials before QRS and slow downstroke of the initial Q wave on the unipolar electrogram at ablation sites were related to favorable outcome after RFCA.

Unusual Polymorphic Ventricular Tachycardia Originating from the Pulmonary Artery

We report a case about a 27-year-old healthy young male who developed syncope during exercise, which was subsequently identified to be attributable to non-sustained polymorphic ventricular tachycardia (VT). Occurrence of polymorphic VT was neither related to a prolonged QT interval nor a fixed short coupling interval. Standard examinations including echocardiography, coronary angiography, isoproterenol infusion study, and cardiac MRI showed no structural heart disease. On the electrophysiology study, activation mapping revealed that a discrete potential preceded the premature ventricular complex (PVC) triggered polymorphic VT, which was recorded just above the pulmonary valve. After radiofrequency ablation at this area, PVC and polymorphic VT disappeared and did not recur after a 2 month follow up.

Unusual Polymorphic Ventricular Tachycardia Originating from the Pulmonary Artery

We report a case about a 27-year-old healthy young male who developed syncope during exercise, which was subsequently identified to be attributable to non-sustained polymorphic ventricular tachycardia (VT). Occurrence of polymorphic VT was neither related to a prolonged QT interval nor a fixed short coupling interval. Standard examinations including echocardiography, coronary angiography, isoproterenol infusion study, and cardiac MRI showed no structural heart disease. On the electrophysiology study, activation mapping revealed that a discrete potential preceded the premature ventricular complex (PVC) triggered polymorphic VT, which was recorded just above the pulmonary valve. After radiofrequency ablation at this area, PVC and polymorphic VT disappeared and did not recur after a 2 month follow up.

Characteristics and Outcomes of Atrial Tachycardia Originating from the Sinus Venosus during Catheter Ablation of Atrial Fibrillation

BACKGROUND AND OBJECTIVES: The sinus venosus (SV) is not a well known source of atrial tachycardia (AT), but it can harbor AT during catheter ablation of atrial fibrillation (AF). SUBJECTS AND METHODS: A total of 1223 patients who underwent catheter ablation for AF were reviewed. Electrophysiological and electrocardiographic characteristics and outcomes after catheter ablation of AT originating from the SV were investigated. RESULTS: Ten patients (0.82%) demonstrated AT from the SV (7 males, 53.9+/-16.0 years, 6 persistent) during ablation of AF. The mean cycle length was 281+/-73 ms. After pulmonary vein isolation and left atrial ablation, AF converted to AT from the SV during right atrial ablation in 2 patients, by rapid atrial pacing after AF termination in 7 patients, and during isoproterenol infusion in 1 patient. Positive P-waves in inferior leads were shown in most patients (90%). The activation sequence of AT was from proximal to distal in the superior vena cava and high to low in the right atrium, which was similar to that of AT from crista terminalis. Fragmented double potentials were recorded during sinus, and a second discrete potential preceded the onset of P wave by 80+/-37 ms during AT. Using 4.4+/-2.7 radiofrequency focal applications, ATs were terminated and became no longer inducible in all. After ablation procedure, two patients showed transient right phrenic nerve palsy. After 19.9+/-14.8 months, all but 1 patient were free of atrial tachyarrhythmia without complications. CONCLUSION: The AT which develops during AF ablation is rarely originated from SV, and its electrophysiologic characteristics may be helpful in guiding effective focal ablation.

Toll-like receptor 9-mediated inhibition of apoptosis occurs through suppression of FoxO3a activity and induction of FLIP expression

Synthetic oligodeoxynucleotides (ODN) with a CpG-motif are recognized by Toll-like receptor 9 (TLR9) and pleiotropic immune responses are elicited. Stimulation of macrophages with TLR9 agonist prevented apoptosis induced by serum deprivation through increased expression of FLICE-like inhibitory protein (FLIP). CpG ODN-mediated anti-apoptosis depended on the TLR9-Akt-FoxO3a signaling pathway. Inhibition of TLR9 by small interfering (si) RNA or an inhibitor suppressed CpG ODN-mediated anti-apoptosis. Analysis of signaling pathways revealed that the anti-apoptotic effect of CpG ODN required phosphorylation of FoxO3a and its translocation from the nucleus to the cytosol. Overexpression of FoxO3a increased apoptosis induced by serum deprivation and CpG ODN blocked these effects through FLIP expression. In contrast, siRNA knock-down of FoxO3a decreased apoptosis by serum deprivation. In addition, Akt activation was involved in CpG ODN-induced phosphorylation of FoxO3a, expression of FLIP, and anti-apoptosis. Taken together, these results demonstrate the involvement of Akt-FoxO3a in TLR9-mediated anti-apoptosis and indicate that FoxO3a is a distinct regulator for FLIP expression.

Resveratrol inhibits foam cell formation via NADPH oxidase 1-mediated reactive oxygen species and monocyte chemotactic protein-1

Resveratrol is a polyphenolic compound in red wine that has anti-oxidant and cardioprotective effects in animal models. Reactive oxygen species (ROS) and monocyte chemotactic protein-1 (MCP-1) play key roles in foam cell formation and atherosclerosis. We studied LPS-mediated foam cell formation and the effect of resveratrol. Resveratrol pretreatment strongly suppressed LPS-induced foam cell formation. To determine if resveratrol affected the expression of genes that control ROS generation in macrophages, NADPH oxidase 1 (Nox1) was measured. Resveratrol treatment of macrophages inhibited LPS-induced Nox1 expression as well as ROS generation, and also suppressed LPS-induced MCP-1 mRNA and protein expression. We investigated the upstream targets of Nox1 and MCP-1 expression and found that Akt-forkhead transcription factors of the O class (FoxO3a) is an important signaling pathway that regulates both genes. These inhibitory effects of resveratrol on Nox1 expression and MCP-1 production may target to the Akt and FoxO3a signaling pathways.

A Study of Educational Need, Attitude and Knowledge toward Menopause in Middle-aged Women / 여성건강간호학회지

PURPOSE: The purpose of this study was to investigate educational needs, knowledge and attitude towards menopause in middle-aged women METHOD: The research design was a descriptive study. The subjects of this study were 231 middle-aged women. Data was collected from a structured questionnaire from October 2 to November 30, 2007. RESULT: The score of educational needs towards menopause was relatively high at 3.83/5. The score of educational needs related to 'Osteoporosis'(3.99 score), 'Cardiovascular disease' (3.91 score), and 'Hormone replacement therapy'(3.87 score) was relatively high. The score of knowledge towards menopause was relatively low at 17.28/30. The score of attitude towards menopause was neutral at 2.3/4. The relationship between knowledge and attitude towards menopause revealed a negative significant correlation (r=-.194, p=.003). The relationship between knowledge and educational needs towards menopause revealed a positive significant correlation (r=0.275, p<.0001). The degree of educational needs of women before menopause is higher than in menopausal women. CONCLUSION: There is a need to develop a continuing educational program according to age and menopause condition. Specialists (Nurses) must give information about menopause for a positive attitude toward menopause.

A Study of Stress of Middle-aged Women with a Senior in High School / 여성건강간호학회지

PURPOSE: The purpose of this study was to investigate the stress caused by having a senior in high school preparing for the college entrance examination, and coping methods of middle aged women in order to have a high quality of life. METHOD: The subjects of this study were 410 middle aged women. The data were collected by a structured questionnaire during September 5 to October 26, 2005. RESULT: The respondents' scores of stress were relatively low. The scores of stress perception related to 'studies record inactivity', 'a bad feeling because their sons and daughters are lazy', and worries about fatigue and health of their sons and daughters' were relatively high. The scores of the coping method related to 'affirmative thought and conduct', and 'sincerity it in the senior in high school student' were relatively high. In subjects with a higher degree(score > or = 3) of stress caused by the senior student in high school the scores of coping methods related to 'projection', 'evasion', and 'perseverance' were relatively higher than the scores of coping methods of subjects with a lower degree (score < 3) of stress. CONCLUSION: Based on the findings of this study, we should develop an integrated support program for middle-aged women. A place must be made where mothers will be able to discuss the education of their children such as on-line group community by mothers.

Arsenic Trioxide Induces A poptosis in Human Colorectal Adenocarcinoma HT-29 Cells Through ROS / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Treatment with arsenic trioxide (As2O3) results in a wide range of cellular effects that includes induction of apoptosis, inhibition of cell growth, promotion or inhibition of cellular differentiation, and inhibition of angiogenesis through a variety of mechanisms. The mechanisms of As2O3-induced cell death have been mainly studied in hematological cancers, and those mechanisms in solid cancers have yet to be clearly defined. In this study, the mechanisms by which As2O3 induces apoptosis in human colorectal adenocarcinoma HT-29 cells were investigated. MATERIALS AND METHODS: To examine the levels of apoptosis, HT-29 cells were treated with As2O3 and then we measured the percentage of Annexin V binding cells, the amount of ROS production and the mitochondrial membrane potential. Western blot analysis was performe to identify the activated caspases after As2O3 exposure, and we compared the possible target molecules of apoptosis. As2O3 treatment induced the loss of the mitochondrial membrane potential and an increase of ROS, as well as activation of caspase-3, -7, -9 and -10. RESULTS: As2O3 induced apoptosis via the production of reactive oxygen species and the loss of the mitochondrial membrane potential. As2O3 induced the activation of caspase-3, -7, -9 and -10. Furthermore, As2O3 treatment downregulates the Mcl-1 and Bcl-2 expressions, and the release of cytochrome c and an apoptosis-inducing factor (AIF). Pretreating the HT-29 cells with N-acetyl-L-cysteine, which is a thiol-containing antioxidant, inhibited the As2O3- Induced Apoptosis and Caspase Activation. CONCLUSION: Taken together, these results suggest that the generation of reactive oxygen species (ROS) by As2O3 might play an important role in the regulation of As2O3-induced apoptosis. This cytotoxicity is mediated through a mitochondria-dependent apoptotic signal pathway in HT-29 cells.

Effect of Human Bcl-2 Gene Expression on the Peripheral Atherosclerotic Lesions of Apolipoprotein E-Deficient Mouse

BACKGROUND AND OBJECTIVES: Bcl-2 protein is related to the inhibition of apoptosis via the mitochondrial pathway and Bcl-2's anti-oxidant effect. During the development of atherosclerosis, apoptosis is known to play an important role in the pathophysiologic behavior of atherosclerotic vascular disease in the medium-sized arteries. Apoptosis may be a compensatory reaction to regulate the cellular density of various tissues during the cellular proliferation process such as happens with tissue injury and during the development of atherosclerosis. The consequences of apoptosis in atherosclerosis may be related to the formation of an acellular lipid core, plaque instability and the loss of vascular wall integrity and remodeling. We sought to determine the effect of Bcl-2 gene expression on the development of primary atherosclerosis in apolipoprotein E deficient mouse, which is one of the typical animal models that are used for the development of peripheral atherosclerosis. MATERIALS AND METHODS: Bcl-2 transgenic mice were cross hybridized with apolipoprotein E deficient mice. Systemic analysis of the distribution and severity of their atherosclerotic lesions was done by dissecting microscopy, and the histological characteristics of the lesions were evaluated in normal chow-fed, 9-month-old apolipoprotein-E deficient/Bcl-2 transgenic mice (n=6) and apolipoprotein-E deficient mice (n=6). RESULTS: The distribution and severity of atherosclerotic lesions at the peripheral arteries were less in the apolipoprotein-E deficient/Bcl-2 transgenic mice. Acellular lipid core formation, destruction of the smooth muscle cell layers in the media and infiltration of inflammatory cells in the adventitia were much less in the apolipoprotein-E deficient/Bcl-2 transgenic mice. The lipid profile was similar in both groups. CONCLUSION: The effect of Bcl-2 gene expression on the peripheral atherosclerosis was related with the inhibition or the delay of atherosclerotic lesion progression, such as the reduction of amount of the acellular lipid core, maintenance of vascular smooth muscle cell integrity and the reduction of adventitial inflammation, and this was achieved regardless of serum cholesterol level.