No abstract available.

BACKGROUND AND OBJECTIVES: An increase in intracellular calcium concentration due to loss of Ca2+ homeostasis triggers arrhythmia or cardiac cell death in the heart. Paracrine factors released from stem cells have beneficial cardioprotective effects. However, the mechanism of modulation of Ca2+ homeostasis by paracrine factors in ischemic myocardium remains unclear. MATERIALS AND METHODS: We isolated rat bone marrow-derived mesenchymal stem cells (MSCs), and prepared paracrine media (PM) from MSCs under hypoxic or normoxic conditions (hypoxic PM and normoxic PM). We induced rat myocardial infarction by left anterior descending ligation for 1 hour, and treated PM into the border region of infarcted myocardium (n=6/group) to identify the alteration in calcium-regulated proteins. We isolated and stained the heart tissue with specific calcium-related antibodies after 11 days. RESULTS: The hypoxic PM treatment increased Ca2+-related proteins such as L-type Ca2+ channel, sarcoplasmic reticulum Ca2+ ATPase, Na+/K+ ATPase, and calmodulin, whereas the normoxic PM treatment increased those proteins only slightly. The sodium-calcium exchanger was significantly reduced by hypoxic PM treatment, compared to moderate suppression by the normoxic PM treatment. CONCLUSION: Our results suggest that hypoxic PM was significantly associated with the positive regulation of Ca2+ homeostasis in infarcted myocardium.
Adenosine Triphosphatases ; Animals ; Antibodies ; Arrhythmias, Cardiac ; Calcium ; Calcium-Transporting ATPases ; Calmodulin ; Cell Death ; Heart ; Homeostasis ; Ligation ; Mesenchymal Stromal Cells ; Myocardial Infarction ; Myocardium* ; Paracrine Communication ; Rats* ; Sarcoplasmic Reticulum ; Sodium-Calcium Exchanger ; Stem Cells

Although quantitative EEG parameters, such as spectral band powers, are sensitive to centrally acting drugs in dose- and time-related manners, changes of the EEG parameters are redundant. It is desirable to reduce multiple EEG parameters to a few components that can be manageable in a real space as well as be considered as parameters representing drug effects. We calculated factor loadings from normalized values of eight relative band powers (powers of 0.5, 1.0~2.0, 2.5~4.0, 4.5~5.5, 6.0~8.0, 8.5~12.0, 12.5~24.5, and 25~49.5 Hz bands expressed as ratios of the power of 0.5-49.5 Hz band) of EEG during pre-drug periods (11:00~12:00) by factor analysis and constructed a two-dimensional canonical space (reference canonical space) by canonical correlation analysis. Eight relative band powers of EEG produced by either physostigmine or yohimbine were reduced to two canonical scores in the reference canonical space. While changes of the band powers produced by physostigmine and yohimbine were too redundant to describe the difference between two drugs, locations of two drugs in the reference canonical space represented the difference between two drug's effects on EEG. Because the distance between two locations in the canonical space (Mahalanobis distance) indicates the magnitude of difference between two different sets of EEG parameters statistically, the canonical scores and the distance may be used to quantitatively and qualitatively describe the dose-dependent and time-dependent effects and also tell similarity and dissimilarity among effects. Then, the combination of power spectral analysis and statistical analysis may help to classify actions of centrally acting drugs.
Animals ; Electroencephalography ; Factor Analysis, Statistical ; Physostigmine ; Rats ; Yohimbine

PURPOSE: To investigate the risk factors of diabetic nephropathy in patients with diabetic retinopathy requiring panretinal photocoagulation (PRP) and the visual prognosis. METHODS: A retrospective review of electronic medical records was conducted at Seoul St. Mary's Hospital, comprising 103 patients with type 2 diabetes mellitus and diabetic retinopathy who underwent PRP from 1996 to 2005. Patients with type 1 diabetes mellitus, non-diabetic renal disease, non-diabetic retinal disease, visually significant ocular disease, high-risk proliferative diabetic retinopathy, and advanced diabetic retinopathy were excluded. The patients were divided into three groups: no nephropathy (group 1, n = 45), microalbuminuria (group 2, n = 16), and advanced nephropathy (group 3, n = 42). Duration of diagnosis of retinopathy and nephropathy, glycosylated hemoglobin, visual acuity, complications, and treatment history were investigated. RESULTS: The mean glycosylated hemoglobin of group 3 (8.4 ± 1.2) was higher than that of group 1 (7.7 ± 1.0) or group 2 (7.7 ± 1.0) (p = 0.04). Mean interval from PRP to diagnosis of nephropathy was 8.8 ± 6.0 years in group 2 and 8.7 ± 4.9 years in group 3. The significant decrease in visual acuity in group 3 (28 eyes, 35.9%) was significantly higher than that in group 1 (15 eyes, 18.1%, p = 0.01) or group 2 (6 eyes, 20.7%, p = 0.03). Only vitreous hemorrhage showed a significantly higher incidence in groups 2 and 3 than in group 1 (p = 0.02). Multivariate regression analysis revealed that female sex and lower glycosylated hemoglobin were significantly associated with a protective effect on development of nephropathy. CONCLUSIONS: In the clinical setting, many patients with PRP-requiring diabetic retinopathy develop nephropathy an average of 8 to 9 years after PRP. Male sex and higher glycosylated hemoglobin could be risk factors of nephropathy.
Diabetes Mellitus, Type 1 ; Diabetes Mellitus, Type 2 ; Diabetic Nephropathies ; Diabetic Retinopathy ; Diagnosis ; Electronic Health Records ; Female ; Hemoglobin A, Glycosylated ; Humans ; Incidence ; Light Coagulation ; Male ; Prognosis ; Retinal Diseases ; Retrospective Studies ; Risk Factors ; Seoul ; Visual Acuity ; Vitreous Hemorrhage

Mainly due to the slanted focus on the mechanism and regulation of neuronal aging, research on astrocyte aging and its modulation during brain aging is scarce. In this study, we established aged astrocyte culture model by long-term culturing. Cellular senescence was confirmed through SA-β-gal staining as well as through the examination of morphological, molecular, and functional markers. RNA sequencing and functional analysis of astrocytes were performed to further investigate the detailed characteristics of the aged astrocyte model. Along with aged phenotypes, decreased astrocytic proliferation, migration, mitochondrial energetic function and support for neuronal survival and differentiation has been observed in aged astrocytes. In addition, increased expression of cytokines and chemokine-related factors including plasminogen activator inhibitor -1 (PAI-1) was observed in aged astrocytes. Using the RNA sequencing results, we searched potential drugs that can normalize the dysregulated gene expression pattern observed in long-term cultured aged astrocytes. Among several candidates, minoxidil, a pyrimidine-derived anti-hypertensive and anti-pattern hair loss drug, normalized the increased number of SA-β-gal positive cells and nuclear size in aged astrocytes. In addition, minoxidil restored up-regulated activity of PAI-1 and increased mitochondrial superoxide production in aged astrocytes.We concluded that long term culture of astrocytes can be used as a reliable model for the study of astrocyte senescence and minoxidil can be a plausible candidate for the regulation of brain aging.

Purpose: This study aims to explore income-based disparities in breast cancer (BC) incidence and stage at presentation in a national population in South Korea, where a National Cancer Screening Program (NCSP) has been implemented. Methods: In 2007, new patients with BC were identified using the Korea Central Cancer Registry database. We calculated adjusted odds ratios (aORs) to evaluate the association between individual income level and the risk of distant stage BC at presentation, adjusting for women’s age, body mass index, disability registration, employment, region of residence, and year of diagnosis. Results: The cumulative age-standardized incidence of BC in the 11 years was highest among women in the richest quintile (2,040 per 100,000 women for 11 years), whereas the proportion of distant stage at presentation was the highest (10.2%) among the medical aid beneficiaries. The aOR of distant stage diagnosis at presentation was higher for lowerincome quintiles, and the risk was the highest in the medical aid beneficiaries (aOR, 2.25;95% confidence interval, 1.97–2.58) than in the richest quintile. The income-based gradient in aORs for distant stage did not differ between younger (< 40 years) and older patients. Conclusion A higher risk of distant stage BC at presentation among the lower-income and medical aid groups in the context of a NCSP was observed. A more focused approach toward women in lower-income groups is necessary to alleviate the disparity in the risk of advanced BC.

Background: Acinar cell carcinoma (ACC) is a rare malignant epithelial neoplasm, which shares many cytomorphological features with other non-ductal pancreatic neoplasms such as pancreatic neuroendocrine neoplasm (PanNEN) and solid-pseudopapillary neoplasm (SPN). Due to the relative rarity of these tumors, pathologists are less familiar with the cytological features, especially on liquid-based cytology (LBC) which has been relatively recently introduced for endoscopic ultrasound-guided fine needle aspiration specimens. Methods: We evaluated the detailed cytological features of 15 histologically confirmed ACC (7 conventional smears [CS], 8 LBC), and compared them with the LBC features of SPN (n = 9) and PanNEN (n = 9). Results: Compared with CS, LBCs of ACC demonstrated significantly less bloody background. All ACCs demonstrated prominent nucleoli and macronucleoli on LBC. On comparison with the LBC features of SPN and PanNEN, most ACCs demonstrated a necrotic background with apoptotic debris while PanNEN and SPN did not show these features. Acinar structures were predominantly observed in ACC, while frequent pseudopapillary structures were seen only in SPN. Prominent nucleoli and macronucleoli were only seen in ACC. Conclusions ACC had characteristic cytological features that could be observed on LBC preparations, such as high cellularity, necrotic/apoptotic background, nuclear tangles, acinar arrangement of cells, and macronucleoli. These findings also help distinguish ACC from PanNEN and SPN on LBC. It is important to be familiar with these features, as an accurate diagnosis on endoscopic ultrasound–guided fine needle aspiration cytology would have impact on the management of the patient.

Endovascular abdominal aortic aneurysm (AAA) repair has been widely used for the treatment of AAA as a safe and efficient method, but endoleaks causing persistent expansion of aneurysm sac may cause aneurysmal rupture and death. Type 3 endoleak is rare but a predominant cause of late rupture. Type 3b endoleak can be misdiagnosed as type 2 endoleak, which is more frequent. Here we report two cases of type 3b endoleak mimicking type 2 endoleak, which were successfully treated by open surgery of partial explantation of the stent-graft and endoaneurysmal interposition graft replacement.
Aneurysm ; Aortic Aneurysm* ; Aortic Aneurysm, Abdominal ; Endoleak* ; Endovascular Procedures ; Methods ; Rupture ; Transplants

PURPOSE: Neutrophils are considered key effector cells in the pathogenic mechanisms of airway inflammation in asthma. This study assessed the activation status of neutrophils in adult asthmatics, and the therapeutic potential of FTY720, a synthetic sphingosine-1-phosphate analog, on activated neutrophils using an in vitro stimulation model. METHODS: We isolated peripheral blood neutrophils (PBNs) from 59 asthmatic patients (including 20 aspirin-exacerbated respiratory disease [AERD] and 39 aspirin-tolerant asthma [ATA] groups). PBNs were stimulated with N-formyl-methionyl-leucyl-phenylalanine (fMLP) or lipopolysaccharide (LPS) and their activation status was determined based on reactive oxygen species (ROS) production, cell surface expression of CD11b, interleukin (IL)-8 and matrix metallopeptidase (MMP)-9 release. PBNs were primed with FTY720 to evaluate its anti-inflammatory action. RESULTS: In vitro PBN stimulation with fMLP or LPS induced a significant increase in ROS/CD11b/IL-8/MMP-9 levels (P < 0.05 for all). In asthmatics, fMLP-induced ROS level was significantly correlated with values of forced expiratory volume in 1 second/forced vital capacity (r = −0.278; P = 0.036), maximal mid-expiratory flow (r = −0.309; P = 0.019) and PC20 methacholine (r = −0.302; P = 0.029). In addition, ROS levels were significantly higher in patients with AERD and in those with severe asthma than in those with ATA or non-severe asthma (P < 0.05 for all). FTY720 treatment could suppress ROS/CD11b levels, and LPS-induced IL-8 and MMP-9 levels (P < 0.05 for all). Responders to FTY720 treatment had significantly higher neutrophil counts in sputum (P = 0.004). CONCLUSIONS: Our findings suggest a useful in vitro PBN stimulation model for evaluating the neutrophil functional status and the therapeutic potentials of neutrophil-targeting candidates in asthmatics.
Adult ; Asthma ; Fingolimod Hydrochloride ; Forced Expiratory Volume ; Humans ; In Vitro Techniques ; Inflammation ; Interleukin-8 ; Interleukins ; Methacholine Chloride ; N-Formylmethionine Leucyl-Phenylalanine ; Neutrophil Activation ; Neutrophils ; Phenotype ; Reactive Oxygen Species ; Sputum ; Vital Capacity

Objectives: Relatively few studies have assessed risk factors for coronavirus disease 2019 (COVID-19) in public facilities used by children and adolescents. This study presents an analysis of a COVID-19 outbreak that occurred in a taekwondo gym in Korea, predominantly among children and adolescents, with the aim of providing insights on managing COVID-19 outbreaks in similar facilities. Methods: All 108 taekwondo gym students and staff received COVID-19 tests. A survey and closed-circuit television analyses were used to identify risk factors. A univariate analysis was conducted, followed by multivariate logistic regression analysis with backward elimination for variables with a significance level <0.10 in the univariate analysis. Results: COVID-19 was confirmed in 30 of 108 subjects at the taekwondo gym (attack rate, 27.8%). The outbreak started in an adult class student. This student transmitted the virus to the staff, who consequently transmitted the virus to adolescent students. In the univariate analysis, the relative risk for younger age (≤9 years) was 2.14 (95% confidence interval [CI], 1.01–4.54; p=0.054), and that for food consumption inside the gym was 2.12 (95% CI, 1.04–4.30; p=0.048). In the multivariate logistic regression analysis, the odds ratio for younger age was 2.96 (95% CI, 1.07–8.20; p=0.036), and that for food consumption inside the gym was 3.00 (95% CI, 1.10–8.17; p=0.032). Conclusion Food consumption inside the facility and young age were significant risk factors for COVID-19 transmission in this taekwondo gym. Food consumption should be prohibited in sports facilities, and infection prevention education for young students is also required.