N-Acetylcysteine Induces Apoptotic, Oxidative and Excitotoxic Neuronal Death in Mouse Cortical Cultures / 전남의대학술지

N-acetylcysteine (NAC) has been used as an antioxidant to prevent oxidative cell death.However, we found NAC itself to induce neuronal death in mouse cortical cultures.Therefore, the current study was performed to investigate the mechanism of neuronal death caused by NAC. Cell death was assessed by measuring lactate dehydrogenase efflux to bathing media after 24-48 h exposure to NAC. NAC (0.1-10 mM) induced neuronal death in a concentration- and exposure time-dependent manner. However, NAC did not injure astrocytes even at a concentration of 10 mM. Also, 10 mM NAC markedly attenuated oxidative astrocyte death induced by 0.5 mM diethyl maleate or 0.25 mM H2O2 . The NMDA receptor antagonist MK-801 (10 μM) markedly attenuated the neuronal death caused by 10 mM NAC, while NBQX did not affect the neuronal death. Cycloheximide (a protein synthesis inhibitor, 0.1 μg/mL) and z-VAD-FMK (a caspase inhibitor, 100 μM) also significantly attenuated neuronal death. Apoptotic features such as chromatin condensation, nuclear fragmentation, and caspase 3 activation were observed 1 h after the NAC treatment. The neuronal death induced by 1 or 10 mM NAC was significantly attenuated by the treatment with 100 μM Trolox or 1 mM ascorbic acid. NAC induced the generation of intracellular reactive oxygen species (ROS), as measured by the fluorescent dye 2’,7’-dichlorofluorescein diacetate. The ROS generation was almost completely abolished by treatment with Trolox or ascorbic acid. These findings demonstrate that NAC can cause oxidative, apoptotic, and excitotoxic neuronal death in mouse neuronal cultures.

Dysphagia Aortica Initially Misdiagnosed as Poststroke Dysphagia: A Case Report / 대한연하장애학회지

Dysphagia aortica is a rare form of mechanical dysphagia characterized by extrinsic compression of the esophagus by the aorta. A 69-year-old male reported experiencing swallowing difficulties for five months, along with nausea, abdominal discomfort, weight loss, and severe reflux. Considering his age and a medical history of hypertension and stenosis of the cerebral artery, poststroke dysphagia was initially suspected. However, brain magnetic resonance imaging revealed no evidence of acute or subacute stroke. Further evaluation was achieved via enhanced chest computed tomography to locate the focus of the systemic inflammation. A thoracic aortic aneurysm about 8.7×5.0 cm in size, with signs of impending rupture, was observed. This case reinforces that a high possibility for dysphagia aortica should be considered under conditions of unclear etiology of dysphagia but the presence of associated symptoms, such as progressive intolerance to solids and ultimately to liquids, weight loss, and nausea.

Respiratory Arrest Induced by Presbyesophagus: A Case Report / 대한연하장애학회지

Presbyesophagus is a unique cause of dysphagia in the elderly, which features incomplete relaxation of the lower esophageal sphincter, dilatation of the esophagus, decreased esophageal peristaltic pressures, abnormal esophageal contractions, and delayed emptying of the esophagus. An 88-year-old woman underwent surgery for a femur fracture.The day after surgery, respiratory arrest occurred during a meal. Breathing resumed after oxygen supply with airway opening. She complained of dysphagia and nausea during a meal, and the videofluoroscopic swallowing study and esophagography showed delayed emptying of the esophagus, abnormal esophageal contraction, and dilatation of the esophagus. This case shows that esophageal dysfunction in the elderly with poor general medical conditions can worsen abruptly.

Fluoxetine Induces Apoptotic and Oxidative Neuronal Death Associated with The Influx of Copper Ions in Cultured Neuronal Cells / 전남의대학술지

We examined the effect of fluoxetine, a selective serotonin reuptake inhibitor antidepressant, on neuronal viability in mouse cortical near-pure neuronal cultures. Addition of fluoxetine to the media for 24 hours induced neuronal death in a concentration-dependent manner. To delineate the mechanisms of fluoxetine-induced neuronal death, we investigated the effects of trolox, cycloheximide (CHX), BDNF, z-VAD-FMK, and various metal-chelators on fluoxetine-induced neuronal death. Neuronal death was assessed by MTT assay. The addition of 20 µM fluoxetine to the media for 24 hours induced 60–70% neuronal death, which was associated with the hallmarks of apoptosis, chromatin condensation and DNA laddering. Fluoxetine-induced death was significantly attenuated by CHX, BDNF, or z-VAD-FMK. Treatment with antioxidants, trolox and ascorbate, also markedly attenuated fluoxetine-induced death. Interestingly, some divalent cation chelators (EGTA, Ca-EDTA, and Zn-EDTA) also markedly attenuated the neurotoxicity. Fluoxetine-induced reactive oxygen species (ROS) generation was measured using the fluorescent dye 2′,7′-dichlorofluorescin diacetate. Trolox and bathocuproine disulfonic acid (BCPS), a cell membrane impermeable copper ion chelator, markedly attenuated the ROS production and neuronal death. However, deferoxamine, an iron chelator, did not affect ROS generation or neurotoxicity. We examined the changes in intracellular copper concentration using a copper-selective fluorescent dye, Phen Green FL, which is quenched by free copper ions. Fluoxetine quenched the fluorescence in neuronal cells, and the quenching effect of fluoxetine was reversed by co-treatment with BCPS, however, not by deferoxamine. These findings demonstrate that fluoxetine could induce apoptotic and oxidative neuronal death associated with an influx of copper ions.

Esophagostomy as an Alternative to Gastrostomy for Dysphagia in Muscular Dystrophy: A Case Report / 대한연하장애학회지

Many people with muscular dystrophy develop dysphagia that can result in an inability to use the oral route in severe cases. In such cases, an alternative feeding method is selected, including a nasogastric tube or a gastrostomy.This case report describes a 40-year-old man with muscular dystrophy who was managed for swallowing difficulty and respiratory failure. Oromotor muscle weakness caused prolonged mealtimes, difficulty with swallowing a solidform diet, aspiration signs, and weight loss. Consequently, an alternative feeding method was required. An abdominal radiograph showed massive aerophagia, and the transverse colon was located over the stomach. As a result, the colon interfered with the puncture route, which could lead to colon perforation. Therefore, cervical esophagostomy was selected, where the patient obtained nutrition through a cervical esophagostomy tube. This case showed that when gastrostomy cannot be performed due to aerophagia, cervical esophagostomy can successfully support nutrition for the mid to long-term in muscular dystrophy patients.

Recent Trends in Transurethral Surgeries and Urological Outpatient Procedures: a Nationwide Populationbased Cohort Study

Background@#Demographic change and advances in technology affect transurethral surgery and outpatient procedures in the urologic field. There are few population-based studies that accurately assess the trend of transurethral surgery and outpatient procedures including diagnostic tests. We investigated the recent epidemiologic trends in transurethral surgeries and urological outpatient procedures from 2009 to 2016 in Korea using the entire populationbased cohort. @*Methods@#We analyzed medical service claim data of transurethral surgery, urological outpatient procedures submitted by medical service providers from the Health Insurance Review and Assessment Service from 2009 to 2016. @*Results@#Transurethral ureter surgery increased by 134.9% from 14,635 in 2009 to 34,382 in 2016 (B = 2,698; R 2 = 0.98; P 2 = 0.97; P 2 = 0.04; P = 0.617) and urethral surgery (B = −12; R 2 = 0.18; P = 0.289). The significantly increasing trends in cystoscopy (B = 5,260; R 2 = 0.95; P 2 = 0.99; P 2 = 0.77; P = 0.003) and electrical stimulation treatment (EST: B = −1,034; R 2= 0.87; P < 0.001) significantly decreased. @*Conclusion@#In Korea, transurethral ureter surgery and transurethral bladder surgery have been continuously increasing. Transurethral prostate surgery and transurethral urethral surgery remained constant with no increase or decrease. Cystoscopy and uroflowmetry continue to increase, while UDS and EST continue to decrease.

Association between the Levofloxacin Plasma Concentration and Neurological Adverse Events in an Elderly Patient

No abstract available.

Clinical and Radiological Changes after Microfracture of Knee Chondral Lesions in Middle-Aged Asian Patients

BACKGROUND: Although microfracture is widely accepted as an effective treatment option for knee chondral lesions, little is known about the deterioration of clinical outcomes and radiological progression in middle-aged patients. Therefore, this study was conducted to evaluate the clinical and radiological changes after microfracture of knee chondral lesions in middle-aged Asian patients. METHODS: A total of 71 patients were included in the study. They were between the ages of 40 and 60 years and underwent arthroscopic microfracture for localized full-thickness cartilage defects of the knee from January 2000 to September 2015. The recovery status of chondral lesions was assessed by using the magnetic resonance observation of cartilage repair tissue (MOCART) score in postoperative magnetic resonance imaging (MRI). Clinical and radiological results were reviewed, and survival rate with conversion to arthroplasty or osteotomy as an end point was evaluated. RESULTS: The mean age of the patients at surgery was 51.3 ± 4.7 years (range, 40 to 60 years), and the mean follow-up period was 7.2 ± 2.6 years (range, 1.0 to 17.4 years). The MOCART scores of 32 patients at mean postoperative 2.1 years showed three cases (9%) of full recovery, two cases (7%) of hyperplastic recovery, 23 cases (70%) with more than 50% filling, and four cases (14%) with less than 50% filling. Clinical scores improved significantly at 1 year after surgery (p < 0.05); however, the scores deteriorated over time after postoperative 1 year, and the mean values reached preoperative levels at postoperative 10 years. Significant radiological progression of arthritis (Kellgren-Lawrence grade) was observed at 5 years after surgery. Four patients underwent total knee arthroplasty during follow-up. CONCLUSIONS: Most patients showed more than 50% of defect filling at 2 years after surgery on MRI. Clinical results of microfracture of knee chondral lesion showed the best improvement at postoperative 1 year but gradually worsened thereafter until postoperative 10 years. Radiological progression of arthritis was observed from 5 years after surgery.

Late-Onset Spinal Subdural Hematoma after Acupuncture

Acupuncture is generally regarded as a safe procedure and as a popular treatment for patients with musculoskeletal disorders. We report a case of a 47-year-old male patient with late-onset tetraplegia, developed after acupuncture. He had no trauma, medical, and social history relevant to tetraplegia. Right after the acupuncture, he felt discomfort in his right arm. After 6 days, all 4 extremity weakness developed. Whole-spine magnetic resonance imaging revealed the presence of spinal subdural hematoma extending from the C5 vertebra to the coccyx level. Hand coordination dysfunction, neurogenic bladder, and neuropathic pain were other symptoms. After the management, he recovered muscle strength, but incomplete bladder control and neuralgia were sustained. It is important to be aware of the possibilities of severe complications after acupuncture.

Effects of NADPH Oxidase Inhibitors and Mitochondria-Targeted Antioxidants on Amyloid β₁₋₄₂-Induced Neuronal Deaths in Mouse Mixed Cortical Cultures / 전남의대학술지

The Amyloid β peptide (Aβ) is a main component of senile plaques in Alzheimer's disease. Currently, NADPH oxidase (NOX) and mitochondria are considered as primary sources of ROS induced by Aβ. However, the contribution of NOX and mitochondria to Aβ-induced ROS generation has not been well defined. To delineate the relative involvement of NOX and mitochondria in Aβ-induced ROS generation and neuronal death in mouse cortical cultures, we examined the effect of NOX inhibitors, apocynin and AEBSF, and the mitochondria-targeted antioxidants (MTAs), mitotempol and mitoquinone, on Aβ-induced ROS generation and neuronal deaths. Cell death was assessed by measuring lactate dehydrogenase efflux in bathing media at 24 and 48 hrs after exposure to Aβ₁₋₄₂. Aβ₁₋₄₂ induced dose- and time-dependent neuronal deaths in cortical cultures. Treatment with 20 µM Aβ₁₋₄₂ markedly and continuously increased not only the DHE fluorescence (intracellular ROS signal), but also the DHR123 fluorescence (mitochondrial ROS signal) up to 8 hrs. Treatment with apocynin or AEBSF selectively suppressed the increase in DHE fluorescence, while treatment with mitotempol selectively suppressed the increase in DHR123 fluorescence. Each treatment with apocynin, AEBSF, mitotempol or mitoquinone significantly attenuated the Aβ₁₋₄₂-induced neuronal deaths. However, any combined treatment with apocynin/AEBSF and mitotempol/mitoquinone failed to show additive effects. These findings indicate that 20 µM Aβ₁₋₄₂ induces oxidative neuronal death via inducing mitochondrial ROS as well as NOX activation in mixed cortical cultures, but combined suppression of intracellular and mitochondrial ROS generation fail to show any additive neuroprotective effects against Aβ neurotoxicity.

NADPH Oxidase Mediates β-Amyloid Peptide-Induced Neuronal Death in Mouse Cortical Cultures / 전남의대학술지

β-Amyloid peptide (Aβ) is the main component of senile plaques in patients with Alzheimer's disease, and is known to be a main pathogenic factor of the disease. Recent evidence indicates that activation of NADPH oxidase (NOX) in microglia or astrocytes may be a source of Aβ-induced reactive oxygen species (ROS). We investigated the role of neuronal NOX in Aβ-induced neuronal death in mouse mixed cortical cultures. Cell death was assessed by measuring lactate dehydrogenase efflux to bathing media 24 or 48 hr after exposure to Aβ₂₅₋₃₅, a fragment of Aβ with an equivalent neurotoxic effect. Aβ₂₅₋₃₅ induced neuronal death in concentration- and time- dependent manners with apoptotic features. Neuronal death was significantly attenuated, not only by anti-apoptotic drugs, such as z-VAD-fmk and cycloheximide, but also by antioxidants, such as trolox, ascorbic acid, and epigallocatethin gallate. We also demonstrated that treatment with 20 µM Aβ₂₅₋₃₅ increased fluorescent signals in mixed cortical cultures, but produced only weak signals in pure astrocyte cultures in the presence of 2',7'-dichlorofluorescin diacetate (DCF-DA), an indicator for intracellular ROS. Increased DCF-DA fluorescence was markedly inhibited, not only by trolox, but also by selective NOX inhibitors, such as apocynin and AEBSF. Western blot analyses revealed that Aβ₂₅₋₃₅ increased the expression of gp91phox, a main subunit of NOX in cells. The above antioxidants, apocynin, and AEBSF significantly attenuated neuronal death induced by Aβ₂₅₋₃₅. Furthermore, the gp91phox-specific siRNA-based knockdown of NOX significantly inhibited neuronal death. These results suggest that activation of neuronal NOX is involved in Aβ25-35-induced neuronal death.

JPH203, a selective L-type amino acid transporter 1 inhibitor, induces mitochondria-dependent apoptosis in Saos2 human osteosarcoma cells

Most normal cells express L-type amino acid transporter 2 (LAT2). However, L-type amino acid transporter 1 (LAT1) is highly expressed in many tumor cells and presumed to support their increased growth and proliferation. This study examined the effects of JPH203, a selective LAT1 inhibitor, on cell growth and its mechanism for cell death in Saos2 human osteosarcoma cells. FOB human osteoblastic cells and Saos2 cells expressed LAT1 and LAT2 together with their associating protein 4F2 heavy chain, but the expression of LAT2 in the Saos2 cells was especially weak. JPH203 and BCH, a non-selective L-type amino acid transporter inhibitor, potently inhibited L-leucine uptake in Saos2 cells. As expected, the intrinsic ability of JPH203 to inhibit L-leucine uptake was far more efficient than that of BCH in Saos2 cells. Likewise, JPH203 and BCH inhibited Saos2 cell growth with JPH203 being superior to BCH in this regard. Furthermore, JPH203 increased apoptosis rates and formed DNA ladder in Saos2 cells. Moreover, JPH203 activated the mitochondria-dependent apoptotic signaling pathway by upregulating pro-apoptotic factors, such as Bad, Bax, and Bak, and the active form of caspase-9, and downregulating anti-apoptotic factors, such as Bcl-2 and Bcl-xL. These results suggest that the inhibition of LAT1 activity via JPH203, which may act as a potential novel anti-cancer agent, leads to apoptosis mediated by the mitochondria-dependent intrinsic apoptotic signaling pathway by inducing the intracellular depletion of neutral amino acids essential for cell growth in Saos2 human osteosarcoma cells.

NADPH Oxidase Mediates β-Amyloid Peptide-Induced Neuronal Death in Mouse Cortical Cultures / 전남의대학술지

β-Amyloid peptide (Aβ) is the main component of senile plaques in patients with Alzheimer's disease, and is known to be a main pathogenic factor of the disease. Recent evidence indicates that activation of NADPH oxidase (NOX) in microglia or astrocytes may be a source of Aβ-induced reactive oxygen species (ROS). We investigated the role of neuronal NOX in Aβ-induced neuronal death in mouse mixed cortical cultures. Cell death was assessed by measuring lactate dehydrogenase efflux to bathing media 24 or 48 hr after exposure to Aβ₂₅₋₃₅, a fragment of Aβ with an equivalent neurotoxic effect. Aβ₂₅₋₃₅ induced neuronal death in concentration- and time- dependent manners with apoptotic features. Neuronal death was significantly attenuated, not only by anti-apoptotic drugs, such as z-VAD-fmk and cycloheximide, but also by antioxidants, such as trolox, ascorbic acid, and epigallocatethin gallate. We also demonstrated that treatment with 20 µM Aβ₂₅₋₃₅ increased fluorescent signals in mixed cortical cultures, but produced only weak signals in pure astrocyte cultures in the presence of 2',7'-dichlorofluorescin diacetate (DCF-DA), an indicator for intracellular ROS. Increased DCF-DA fluorescence was markedly inhibited, not only by trolox, but also by selective NOX inhibitors, such as apocynin and AEBSF. Western blot analyses revealed that Aβ₂₅₋₃₅ increased the expression of gp91phox, a main subunit of NOX in cells. The above antioxidants, apocynin, and AEBSF significantly attenuated neuronal death induced by Aβ₂₅₋₃₅. Furthermore, the gp91phox-specific siRNA-based knockdown of NOX significantly inhibited neuronal death. These results suggest that activation of neuronal NOX is involved in Aβ25-35-induced neuronal death.

Immunostimulatory Activity of Apios Tuber Extract on RAW264.7 Macrophage Cells

Apios americana Medik tubers are medicinal foods with anti-cancer and anti-inflammatory activities. However, mechanisms of immunostimulatory action of the Apios tuber extract (ATE) on macrophages have not been elucidated. In the present study, we investigated whether ATE could modulate immune responses, such as production of nitric oxide (NO), proinflammatory cytokines, and transcription factors, in RAW264.7 macrophage cells. ATE significantly increased the production of NO and proinflammatory cytokines such as interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α), and induced the mRNA and protein levels of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) and proinflammatory cytokines in a dose-dependent manner. Furthermore, Western blot analysis revealed that ATE activated the transcription factor Nuclear Factor-κB and mitogen-activated protein kinases signaling cascades, including extracellular signal-regulated kinase, c-Jun N-terminal kinase, and p38 kinase. In addition, we found that ATE induced the activation of macrophages through upregulation of toll-like receptor 4 (TLR4) and TLR2. Taken together, these findings indicate that ATE possesses a potential as a functional food with immunostimulatory activity.

Influence of Thromboxane A₂ on the Regulation of Adenosine Triphosphate-Sensitive Potassium Channels in Mouse Ventricular Myocytes

BACKGROUND AND OBJECTIVES: Adenosine triphosphate (ATP)-sensitive potassium (K(ATP)) channels play an important role in myocardial protection. We examined the effects of thromboxane A₂ on the regulation of K(ATP) channel activity in single ventricular myocytes. SUBJECTS AND METHODS: Single ventricular myocytes were isolated from the hearts of adult Institute of Cancer Research (ICR) mice by enzymatic digestion. Single channel activity was recorded by excised inside-out and cell-attached patch clamp configurations at -60 mV holding potential during the perfusion of an ATP-free K-5 solution. RESULTS: In the excised inside-out patches, the thromboxane A₂ analog, U46619, decreased the K(ATP) channel activity in a dose-dependent manner; however, the thromboxane A₂ receptor antagonist, SQ29548, did not significantly attenuate the inhibitory effect of U46619. In the cell-attached patches, U46619 inhibited dinitrophenol (DNP)-induced K(ATP) channel activity in a dose-dependent manner, and SQ29548 attenuated the inhibitory effects of U46619 on DNP-induced K(ATP) channel activity. CONCLUSION: Thromboxane A₂ may inhibit K(ATP) channel activity, and may have a harmful effect on ischemic myocardium.

Influence of Thromboxane A₂ on the Regulation of Adenosine Triphosphate-Sensitive Potassium Channels in Mouse Ventricular Myocytes

BACKGROUND AND OBJECTIVES: Adenosine triphosphate (ATP)-sensitive potassium (K(ATP)) channels play an important role in myocardial protection. We examined the effects of thromboxane A₂ on the regulation of K(ATP) channel activity in single ventricular myocytes. SUBJECTS AND METHODS: Single ventricular myocytes were isolated from the hearts of adult Institute of Cancer Research (ICR) mice by enzymatic digestion. Single channel activity was recorded by excised inside-out and cell-attached patch clamp configurations at -60 mV holding potential during the perfusion of an ATP-free K-5 solution. RESULTS: In the excised inside-out patches, the thromboxane A₂ analog, U46619, decreased the K(ATP) channel activity in a dose-dependent manner; however, the thromboxane A₂ receptor antagonist, SQ29548, did not significantly attenuate the inhibitory effect of U46619. In the cell-attached patches, U46619 inhibited dinitrophenol (DNP)-induced K(ATP) channel activity in a dose-dependent manner, and SQ29548 attenuated the inhibitory effects of U46619 on DNP-induced K(ATP) channel activity. CONCLUSION: Thromboxane A₂ may inhibit K(ATP) channel activity, and may have a harmful effect on ischemic myocardium.

Anatomic Double-Bundle Anterior Cruciate Ligament Reconstruction Using an Outside-in Technique: Two- to Six-Year Clinical and Radiological Follow-up

PURPOSE: We evaluated the clinical and radiological outcomes of double-bundle anterior cruciate ligament (ACL) reconstruction using an outside-in technique with a follow-up of two- to six-years, especially in terms of the sports activity level and radiological degeneration. MATERIALS AND METHODS: Sixty-seven patients who were available for a minimum two-year follow-up after double-bundle ACL reconstruction using an outside-in technique were retrospectively evaluated. The mean follow-up period was 43.7 months. The knee function and stability were evaluated before the operation, one year after the operation (short-term follow-up), and more than two years after the operation (last follow-up). RESULTS: Regarding the knee function, the Lysholm score, International Knee Documentation Committee (IKDC) evaluation, and hop test showed significant improvement. Regarding the stability, the Lachman test, pivot shift test, KT-2000 arthrometer data, and anterior drawer radiographs using Telos showed significant improvement. Regarding the sports activity level, the patients who returned to pre-injury level activity was 68.7% according to the Tegner activity score and 76.1% according to the Cincinnati sports activity scale score. The incidence of aggravated degeneration or development of greater than IKDC grade A degeneration after surgery was 10.4%. CONCLUSIONS: Double-bundle ACL reconstruction using an outside-in technique showed favorable clinical and radiological outcomes with respect to the knee function and stability, joint degeneraion, and, especially, return to pre-injury sports activity.

Effects of Flavonoid Compounds on beta-amyloid-peptide-induced Neuronal Death in Cultured Mouse Cortical Neurons / 전남의대학술지

Excessive accumulation of beta-amyloid peptide (Abeta) is one of the major mechanisms responsible for neuronal death in Alzheimer's disease. Flavonoids, primarily antioxidants, are a group of polyphenolic compounds synthesized in plant cells. The present study aimed to identify flavonoid compounds that could inhibit Abeta-induced neuronal death by examining the effects of various flavonoids on the neurotoxicity of Abeta fragment 25-35 (Abeta25-35) in mouse cortical cultures. Abeta25-35 induced concentration- and exposure-time-dependent neuronal death. Neuronal death induced by 20 microM Abeta25-35 was significantly inhibited by treatment with either Trolox or ascorbic acid. Among 10 flavonoid compounds tested [apigenin, baicalein, catechin, epicatechin, epigallocatechin gallate (EGCG), kaempferol, luteolin, myricetin, quercetin, and rutin], all except apigenin showed strong 1,1-diphenyl-2-pycrylhydrazyl (DPPH) scavenging activity under cell-free conditions. The flavonoid compounds except apigenin at a concentration of 30 microM also significantly inhibited neuronal death induced by 20 microM Abeta25-35 at the end of 24 hours of exposure. Epicatechin, EGCG, luteolin, and myricetin showed more potent and persistent neuroprotective action than did the other compounds. These results demonstrated that oxidative stress was involved in Abeta-induced neuronal death, and antioxidative flavonoid compounds, especially epicatechin, EGCG, luteolin, and myricetin, could inhibit neuronal death. These findings suggest that these four compounds may be developed as neuroprotective agents against Alzheimer's disease.

Effects of Flavonoid Compounds on beta-amyloid-peptide-induced Neuronal Death in Cultured Mouse Cortical Neurons / 전남의대학술지

Excessive accumulation of beta-amyloid peptide (Abeta) is one of the major mechanisms responsible for neuronal death in Alzheimer's disease. Flavonoids, primarily antioxidants, are a group of polyphenolic compounds synthesized in plant cells. The present study aimed to identify flavonoid compounds that could inhibit Abeta-induced neuronal death by examining the effects of various flavonoids on the neurotoxicity of Abeta fragment 25-35 (Abeta25-35) in mouse cortical cultures. Abeta25-35 induced concentration- and exposure-time-dependent neuronal death. Neuronal death induced by 20 microM Abeta25-35 was significantly inhibited by treatment with either Trolox or ascorbic acid. Among 10 flavonoid compounds tested [apigenin, baicalein, catechin, epicatechin, epigallocatechin gallate (EGCG), kaempferol, luteolin, myricetin, quercetin, and rutin], all except apigenin showed strong 1,1-diphenyl-2-pycrylhydrazyl (DPPH) scavenging activity under cell-free conditions. The flavonoid compounds except apigenin at a concentration of 30 microM also significantly inhibited neuronal death induced by 20 microM Abeta25-35 at the end of 24 hours of exposure. Epicatechin, EGCG, luteolin, and myricetin showed more potent and persistent neuroprotective action than did the other compounds. These results demonstrated that oxidative stress was involved in Abeta-induced neuronal death, and antioxidative flavonoid compounds, especially epicatechin, EGCG, luteolin, and myricetin, could inhibit neuronal death. These findings suggest that these four compounds may be developed as neuroprotective agents against Alzheimer's disease.

Design and Methodology for the Korean Observational and Escitalopram Treatment Studies of Depression in Acute Coronary Syndrome: K-DEPACS and EsDEPACS

Depression is common after acute coronary syndrome (ACS), adversely affecting cardiac course and prognosis. There have been only a few evidence-based treatment options for depression in ACS. Accordingly, we planned the Korean Depression in ACS (K-DEPACS) study, which investigated depressive disorders in patients with ACS using a naturalistic prospective design, and the Escitalopram for DEPACS (EsDEPACS) trial, which assessed the efficacy and safety of escitalopram for treating major or minor depression in patients with ACS. Participants in the K-DEPACS study were consecutively recruited from patients with ACS who were recently hospitalized at Chonnam National University Hospital, Gwangju, South Korea. Diagnoses were confirmed by coronary angiography from 2005. Data on depressive and cardiovascular characteristics were obtained at 2 weeks, 3 months, 12 months, and every 6 months thereafter following the index ACS admission. The K-DEPACS participants who met the DSM-IV criteria for major or minor depressive disorder were randomly assigned to groups in the 24-week, double-blind, placebo-controlled EsDEPACS trial beginning in 2007. The outcome of treatments for depressive and other psychiatric symptoms, issues related to safety, including general adversity, and cardiovascular factors were assessed. The K-DEPACS study can significantly contribute to research on the complex relationships between depression and ACS. The results of the EsDEPACS trial provide an additional treatment option for clinicians treating these patients.