Aging effects on the diurnal patterns of gut microbial composition in male and female mice

Composition of the gut microbiota changes with aging and plays an important role in age-associated disease such as metabolic syndrome, cancer, and neurodegeneration. The gut microbiota composition oscillates through the day, and the disruption of their diurnal rhythm results in gut dysbiosis leading to metabolic and immune dysfunctions. It is well documented that circadian rhythm changes with age in several biological functions such as sleep, body temperature, and hormone secretion. However, it is not defined whether the diurnal pattern of gut microbial composition is affected by aging. To evaluate aging effects on the diurnal pattern of the gut microbiome, we evaluated the taxa profiles of cecal contents obtained from young and aged mice of both sexes at daytime and nighttime points by 16S rRNA gene sequencing. At the phylum level, the ratio of Firmicutes to Bacteroidetes and the relative abundances of Verrucomicrobia and Cyanobacteria were increased in aged male mice at night compared with that of young male mice. Meanwhile, the relative abundances of Sutterellaceae, Alloprevotella, Lachnospiraceae UCG-001, and Parasutterella increased in aged female mice at night compared with that of young female mice. The Lachnospiraceae NK4A136 group relative abundance increased in aged mice of both sexes but at opposite time points. These results showed the changes in diurnal patterns of gut microbial composition with aging, which varied depending on the sex of the host. We suggest that disturbed diurnal patterns of the gut microbiome can be a factor for the underlying mechanism of age-associated gut dysbiosis.

Interaction of promyelocytic leukemia/p53 affects signal transducer and activator of transcription-3 activity in response to oncostatin M

Promyelocytic leukemia (PML) gene, through alternative splicing of its Cterminal region, generates several PML isoforms that interact with specific partners and perform distinct functions. The PML protein is a tumor suppressor that plays an important role by interacting with various proteins. Herein, we investigated the effect of the PML isoforms on oncostatin M (OSM)-induced signal transducer and activator of transcription-3 (STAT-3) transcriptional activity. PML influenced OSMinduced STAT-3 activity in a cell type-specific manner, which was dependent on the p53 status of the cells but regardless of PML isoform. Interestingly, overexpression of PML exerted opposite effects on OSM-induced STAT-3 activity in p53 wild-type and mutant cells. Specifically, overexpression of PML in the cell lines bearing wild-type p53 (NIH3T3 and U87-MG cells) decreased OSM-induced STAT-3 transcriptional activity, whereas overexpression of PML increased OSM-induced STAT-3 transcriptional activity in mutant p53-bearing cell lines (HEK293T and U251-MG cells). When wild-type p53 cells were co-transfected with PML-IV and R273H-p53 mutant, OSM-mediated STAT-3 transcriptional activity was significantly enhanced, compared to that of cells which were transfected with PML-IV alone; however, when cells bearing mutant p53 were co-transfected with PML-IV and wild-type p53, OSM-induced STAT-3 transcriptional activity was significantly decreased, compared to that of transfected cells with PML-IV alone. In conclusion, PML acts together with wild-type or mutant p53 and influences OSM-mediated STAT-3 activity in a negative or positive manner, resulting in the aberrant activation of STAT-3 in cancer cells bearing mutant p53 probably might occur through the interaction of mutant p53 with PML.

Interaction of promyelocytic leukemia/p53 affects signal transducer and activator of transcription-3 activity in response to oncostatin M

Promyelocytic leukemia (PML) gene, through alternative splicing of its Cterminal region, generates several PML isoforms that interact with specific partners and perform distinct functions. The PML protein is a tumor suppressor that plays an important role by interacting with various proteins. Herein, we investigated the effect of the PML isoforms on oncostatin M (OSM)-induced signal transducer and activator of transcription-3 (STAT-3) transcriptional activity. PML influenced OSMinduced STAT-3 activity in a cell type-specific manner, which was dependent on the p53 status of the cells but regardless of PML isoform. Interestingly, overexpression of PML exerted opposite effects on OSM-induced STAT-3 activity in p53 wild-type and mutant cells. Specifically, overexpression of PML in the cell lines bearing wild-type p53 (NIH3T3 and U87-MG cells) decreased OSM-induced STAT-3 transcriptional activity, whereas overexpression of PML increased OSM-induced STAT-3 transcriptional activity in mutant p53-bearing cell lines (HEK293T and U251-MG cells). When wild-type p53 cells were co-transfected with PML-IV and R273H-p53 mutant, OSM-mediated STAT-3 transcriptional activity was significantly enhanced, compared to that of cells which were transfected with PML-IV alone; however, when cells bearing mutant p53 were co-transfected with PML-IV and wild-type p53, OSM-induced STAT-3 transcriptional activity was significantly decreased, compared to that of transfected cells with PML-IV alone. In conclusion, PML acts together with wild-type or mutant p53 and influences OSM-mediated STAT-3 activity in a negative or positive manner, resulting in the aberrant activation of STAT-3 in cancer cells bearing mutant p53 probably might occur through the interaction of mutant p53 with PML.

Hangover relieving and antioxidant effects of Gynostemma pentaphyllum (Thunb.) Makino and/or Hovenia dulcis Thunb. extracts

The present study attempts to study alcohol metabolizing and antioxidant properties of Gynostemma pentaphyllum(Thunb.) Makino distillate (GPD) and combination effects with Hovenia dulcis Thunb. extract (HDE) on these activities.The alcohol-metabolizing activity of GPD with/without HDE was determined by assessing alcohol dehydrogenase(ADH) and acetaldehyde dehydrogenase (ALDH) activities. To define the effect of GPD with/without HDE on alcoholmetabolism, antioxidant activities and total phenolic content of GPD with/without HD extract were evaluated using2-diphenyl-1-picrylhydrazyl free radical scavenging, ferrous chelating assays, and the Folin–Ciocalteu method.Cytotoxicity against human normal liver CHANG cells was also evaluated using the 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. GPD treatment alone or in combination with HDE significantly increased ADHand ALDH activities; combined treatment was most effective. Total phenolic and flavonoid contents were greater incombination than the level found in GPD alone. GPD revealed a synergistic antioxidant effect when combined withHDE. GPD and/or HDE had no antiproliferative activity against the normal liver cell line. These results suggest thatGPD-HDE combination is the possible natural resource for the management of alcohol-induced liver injury.

Predictors of Emotional Labor and Resilience on Clinical Competency in Nursing Students / 한국간호교육학회지

PURPOSE: The purpose of this study was to investigate predictors of emotional labor and resilience on clinical competence in nursing students. METHODS: A cross-sectional, descriptive study was distributed to 120 nursing students. Structured questionnaires addressing emotional labor, resilience, and clinical competence were employed. Descriptive statistics, independent t-test, one-way ANOVA, Pearson correlation coefficient, and regression were used to analyze the data. RESULTS: A total of 116 surveys were analyzed. Satisfaction of clinical practice and major showed statistically significant differences in clinical competence (F=6.59, p=.002; F=11.32, p<.001, respectively). Clinical competence was positively associated with resilience (r=.67, p<.001). Regression analyses showed that satisfaction of clinical practice and major, and resilience were statistically significant in predicting clinical competence with the explanatory power of 46.4% (F=20.91, p<.001). CONCLUSION: The results showed that resilience was the critical predictor of clinical competence in nursing students. It is therefore necessary to develop resilience programs to help improve clinical competence in nursing students.

Aberrant Promoter Hypomethylation of Sortilin 1: A Moyamoya Disease Biomarker / 대한뇌졸중학회지

BACKGROUND AND PURPOSE: The pathogenesis of moyamoya disease (MMD) remains poorly understood, and no reliable molecular biomarkers for MMD have been identified to date. The present study aimed to identify epigenetic biomarkers for use in the diagnosis of MMD. METHODS: We performed integrated analyses of gene expression profiles and DNA methylation profiles in endothelial colony forming cells (ECFCs) from three patients with MMD and two healthy individuals. Candidate gene mRNA expression and DNA methylation status were further validated using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and pyrosequencing analysis of an expanded ECFC sample set from nine patients with MMD and ten controls. We evaluated the diagnostic accuracy of the potential biomarkers identified here using receiver operating characteristic curve analyses and further measured major angiogenic factor expression levels using a tube formation assay and RT-qPCR. RESULTS: Five candidate genes were selected via integrated analysis; all five were upregulated by hypomethylation of specific promoter CpG sites. After further validation in an expanded sample set, we identified a candidate biomarker gene, sortilin 1 (SORT1). DNA methylation status at a specific SORT1 promoter CpG site in ECFCs readily distinguished patients with MMD from the normal controls with high accuracy (area under the curve 0.98, sensitivity 83.33%, specificity 100%). Furthermore, SORT1 overexpression suppressed endothelial cell tube formation and modulated major angiogenic factor and matrix metalloproteinase-9 expression, implying SORT1 involvement in MMD pathogenesis. CONCLUSIONS: Our findings suggest that DNA methylation status at the SORT1 promoter CpG site may be a potential biomarker for MMD.

Increase in Anti-Gal IgM Level is Associated With Early Graft Failure in Intraportal Porcine Islet Xenotransplantation

BACKGROUND: Anti-Gal is a major antibody induced in non-human primates (NHPs) after xenotransplantation. To understand the mechanism of graft rejection, we investigated the association between anti-Gal responses and graft failure in NHP recipients of porcine islet transplantation (PITx). METHODS: Intraportal PITx was performed in 35 diabetic NHPs, and graft function was monitored. Early graft failure (EGF) was defined as loss of graft function within a month after PITx. Seven, 19, nine NHPs received immunosuppression (IS) without CD40 pathway blockade (Group I), with anti-CD154 (Group II), and with anti-CD40 (Group III), respectively. The anti-Gal levels on day 0 and day 7 of PITx were measured by ELISA. RESULTS: The frequency of EGF was significantly lower in Group II (26.3%) than in Group I (100%, P=0.0012) and Group III (77.8%, P=0.0166). While levels of anti-Gal IgG in Group I and anti-Gal IgM in Group III increased on day 7 compared with day 0 (P=0.0156 and 0.0273), there was no increase in either on day 7 in Group II. The ratio of anti-Gal IgM or IgG level on day 7 to that on day 0 (Ratio7/0) was significantly higher in recipients with EGF than without EGF (P=0.0009 and 0.0027). ROC curve analysis of anti-Gal IgM Ratio7/0 revealed an area under the curve of 0.789 (P=0.0003). CONCLUSIONS: IS with anti-CD154 suppressed anti-Gal responses and prevented EGF in PITx. Anti-Gal IgM Ratio7/0, being associated with EGF, is a predictive marker for EGF.

A Guide Book for Children and Adolescents to Experience Anatomy and Clinics / 체질인류학회지

The purpose of this study is to enable children and adolescents to experience anatomy and clinics. For the purpose, the ways to use the anatomy educational resources (comics, 3-dimensional images, and 2-dimensional images) and diagnostic tools (stethoscope, sphygmomanometer, pen light, and reflex hammer) were described in a guide book. Following the guide book, students experienced anatomy and clinics in a course of the science museum. They learned anatomy with the comics, then did virtual dissection with the 3-dimensional and 2-dimensional images. Sequentially, with the diagnostic tools, they listened to heart sound, measured blood pressure, and performed light reflex and knee jerk. Through this study, we have found that anatomy and clinics should be experienced pleasantly. The complimentary guide book is expected to be further improved in future, so as to achieve better experience at home, science museum, and school.

Hypocholesterolemic metabolism of dietary red pericarp glutinous rice rich in phenolic compounds in mice fed a high cholesterol diet

BACKGROUND/OBJECTIVES: The purpose of the current study was to investigate the effect of red pericarp glutinous rice rich in polyphenols (Jakwangchalbyeo, red rice) on serum and hepatic levels of cholesterol and hepatic protein expression linked to synthesis and degradation of cholesterol in a hypercholesterolemic mice diet as compared with brown rice. MATERIALS/METHODS: C57BL/6 male mice were randomly divided into four groups (n = 5 each), which were fed different diets for a period of 12 weeks: American Institute of Nutrition (AIN)-93G diet, AIN-93G diet with 2% cholesterol, brown rice with 2% cholesterol, or red rice with 2% cholesterol. RESULT: Consumption of red rice resulted in a significant decrease in serum level of low-density lipoprotein cholesterol and hepatic levels of triglyceride and total-cholesterol. Expression of acyl-coenzyme A cholesterol acyltransferase-2 (ACAT-2), sterol regulatory element binding protein-2 (SREBP-2), and 3-hydroxyl-3-methylglutaryl coenzyme A (HMG-CoA) reductase was decreased, while expression of phosphorylated adenosine monophosphate activated protein kinase (p-AMPK)/AMPK ratio, cholesterol 7-alpha-hydroxylase (CYP7a1), and sterol 12-alpha-hydroxylase (CYP8b1) was increased in mice fed red rice. Brown rice had similar effects on cholesterol metabolism, but the effect of red rice was significantly greater than that of brown rice. CONCLUSIONS: The current study suggested that red rice had a hypocholesterolemic effect by lowering hepatic cholesterol synthesis through ACAT-2, HMG-CoA reductase, and SREBP-2, and by enhancing hepatic cholesterol degradation through CYP7a1 and CYP8b1 in mice fed a hypercholesterolemic diet.

Reciprocal Regulation of TH17 and Regulatory T Cells by Methotrexate and Its Therapeutic Effects in Collagen-induced Arthritis (CIA)

OBJECTIVE: Methotrexate is the first-line drug in treatment of rheumatoid arthritis (RA) exhibiting higher efficacy and better tolerability than most other DMARDs. To have a better understanding of the anti-arthritic mechanism of methotrexate, we investigated the effect of methotrexate on suppressing the autoimmune inflammatory and destructive arthritis in collagen-induced arthritis (CIA) mice. METHODS: The effects of methotrexate on joint inflammation were assessed by clinical scoring and histologic analysis. Levels of cytokines and autoreactive antibodies were analyzed by immunohistochemistry and ELISA. The population of TH17 and Foxp3+ regulatory T (Treg) cells and phosphorylation of their critical transcription activators, STAT3 and STAT5, were examined by fluorescence microscopy and flow cytometry, respectively. RESULTS: Treatment with methotrexate significantly alleviated joint inflammation and cartilage destruction in CIA. Serum levels of total immunoglobulins G, G1, G2a specific to type II collagen were also reduced considerably in methotrexate-treated mice. The drug inhibited the expression of proinflammatory cytokines such as IL-1beta, TNF-alpha, IL-6 and IL-17 in arthritic joints ex vivo as well as by splenocytes in vitro. Moreover, methotrexate treatment resulted in reciprocal modulation of TH17 cells and Foxp3+ regulatory T (Treg) cells in spleen tissues, in which TH17 cells were decreased and Treg cells in number were increased. Subsequent analysis of CD4+T cells showed that phosphorylation of STAT3 was decreased whereas phosphorylation of STAT5 was increased in methotrexate-treated mice. CONCLUSION: Methotrexate treatment effectively suppressed autoimmune arthritis and restored homeostasis of the immune system by reciprocal regulation of TH17 and Treg cells in a mouse model of collagen-induced arthritis.

Balsamic Vinegar Improves High Fat-Induced Beta Cell Dysfunction via Beta Cell ABCA1

BACKGROUND: The aim of this study was to investigate the effects of balsamic vinegar on beta-cell dysfunction. METHODS: In this study, 28-week-old Otsuka Long-Evans Tokushima Fatty (OLETF) rats were fed a normal chow diet or a high-fat diet (HFD) and were provided with tap water or dilute balsamic vinegar for 4 weeks. Oral glucose tolerance tests and histopathological analyses were performed thereafter. RESULTS: In rats fed both the both chow diet and the HFD, the rats given balsamic vinegar showed increased insulin staining in islets compared with tap water administered rats. Balsamic vinegar administration also increased beta-cell ATP-binding cassette transporter subfamily A member 1 (ABCA1) expression in islets and decreased cholesterol levels. CONCLUSION: These findings provide the first evidence for an anti-diabetic effect of balsamic vinegar through improvement of beta-cell function via increasing beta-cell ABCA1 expression.

Evaluation of MolecuTech Real MTB-ID for MTB/NTM Detection Using Direct Specimens / 대한임상미생물학회지

BACKGROUND: The differentiation of Mycobacterium tuberculosis (MTB) from nontuberculous mycobacteria (NTM) is of primary importance for infection control and choice of antimicrobial therapy. The diagnosis of diseases caused by NTM is difficult because NTM are prevalent in the environment and have fastidious properties. In this study, we evaluated the real-time PCR-based MTB/NTM detection kit for its usefulness in discrimination of MTB and NTM species. METHODS: A total of 155 sputum specimens whose AFB staining smear and culture were positive were used for this study. Among them, 59 and 96 samples had been identified as MTB and NTM, respectively. DNA obtained from sputum specimens was subjected to analysis with MolecuTech Real MTB-ID(R) (M&D, Korea) real-time PCR-based MTB/NTM detection kit. Subsequently, the results of MolecuTech Real MTB-ID(R) were compared with AFB staining smear and culture results. RESULTS: The positive rate of MolecuTech Real MTB-ID(R) to detect MTB and NTM was 98.3% (58/59) and 97.9 (94/96), respectively, using sputum specimens. CONCLUSION: For detection of MTB/NTM, the sensitivity and specificity of MolecuTech Real MTB-ID(R) were comparable to those of conventional methods. Therefore, this study suggests the usefulness of real-time PCR-based MolecuTech Real MTB-ID(R) for rapid detection of MTB/NTM from direct specimens.

Myeloid differentiation primary response protein 88 blockade upregulates indoleamine 2,3-dioxygenase expression in rheumatoid synovial fibroblasts

Indoleamine 2,3-dioxygenase (IDO) is a key negative regulator of immune responses and has been implicated in tumor tolerance, autoimmune disease and asthma. IDO was detected in the joint synovial tissue in the inflammatory microenvironment of rheumatoid arthritis (RA), but IDO expression in joint synovial tissue is not sufficient to overcome the inflamed synovial environment. This study aimed to unravel the mechanisms involving the failure to activate tolerogenic IDO in the inflamed joint. We demonstrate that both poly (I:C) and lipopolysaccharide (LPS) induce expression of IDO in synovial fibroblasts. However, inflammatory cytokines such as IL-17, TNF-alpha, IL-12, IL-23 and IL-16 did not induce IDO expression. Poly (I:C) appeared to induce higher IDO expression than did LPS. Surprisingly, toll-like receptor (TLR)4-mediated IDO expression was upregulated after depletion of myeloid differentiation primary response protein 88 (MyD88) in synovial fibroblasts using small interfering RNA (siRNA). IDO, TLR3 and TLR4 were highly expressed in synovial tissue of RA patients compared with that of osteoarthritis patients. In addition, RA patients with severe disease activity had higher levels of expression of IDO, TLR3 and TLR4 in the synovium than patients with mild disease activity. These data suggest that upregulation of IDO expression in synovial fibroblasts involves TLR3 and TLR4 activation by microbial constituents. We showed that the mechanisms responsible for IDO regulation primarily involve MyD88 signaling in synovial fibroblasts, as demonstrated by siRNA-mediated knockdown of MyD88.

Imaging Studies in Mouse Brain Using Clinical 3T MRI Scanner / 의학물리

The purpose of this study was to explore the potentials of a clinical 3T MRI in mouse brains and technical adaptation and optimization. T1-weighted images (T1WI), T2-weighted images (T2WI), FLAIR (Fluid Attenuated Inversion Recovery) images, Gadolinium enhanced T1-weighted images (Gd-T1WI), Diffusion weighted images (DWI) were acquired in brain of 2 mice (weight 20~25 g) with cerebral infarction by occlusion of right middle cerebral artery, 1 hour, 24 hours, 72 hours after infarction and 1 normal mouse brain using clinical 3T MRI scanner. We analyzed differentiation of striatum, ventricle, cerebral cortex, and possibility of detection of acute cerebral infarction. We could differentiate the striatum, ventricle, cerebral cortex on T2WI and on DWI, FLAIR, T1WI, the differentiation of each anatomy of brain was not definite, but acute cerebral infarction was detected on DWI of 1 hour, 24 hours, 72 hours after infarction and on T2WI, FLAIR of 24 hours, 72 hours after infarction. Clinical 3T MRI can be used in differentiation of anatomy of mouse brains and DWI can be helpul in detection of acute cerebral infarction in acute phase. With technical adaptation and optimization clinical 3T MRI can be useful tool for provide preclinical and clinical small animal studies.

Alteration of Ventricular Repolarization by Intracoronary Infusion of Normal Saline in Patients With Variant Angina

BACKGROUND AND OBJECTIVES: During coronary angiography and interventional procedures, catheters that are engaged in a coronary ostium are routinely flushed, typically with normal saline, to expel blood from the catheter or to inject a pharmacologic agent. Saline contains sodium and chloride ions. Such injections may affect the electrophysiologic properties of the myocardium; however, the effect of normal saline on ventricular repolarization has not been established in patients with variant angina. SUBJECTS AND METHODS: We studied 51 consecutive patients with variant angina. Five mL of normal saline (NS) or 5% dextrose solution (DW) were infused into the left coronary artery in random order. We measured the heart rate, QT interval, and T-wave amplitude using Mac-Lac 5.2. RESULTS: The baseline clinical characteristics were not different between the NS {n=30 (14 males); mean age, 56+/-10 years} and the 5% DW groups {n=21 (7 males); mean age, 59+/-10 years}. The changes in the mean corrected QT (QTc) interval were significantly increased at the time of infusion of NS compared to 5% DW (45.1+/-30.3 vs. 20.9+/-23.3 ms, p=0.004). There was a T-wave amplitude change >0.2 mV in at least one-lead in 27 patients (90.0%) during NS infusion compared to 7 patients (33.3%) during 5% DW infusions (p=0.001). No significant changes in heart rate and blood pressure were noted during of the infusions. CONCLUSION: NS was associated with prolongation of ventricular repolarization in patients with variant angina.

In Vitro Antimicrobial Susceptibility of Mycobacterium abscessus in Korea

Mycobacterium abscessus is the second most common etiology of pulmonary disease caused by nontuberculous mycobacteria in Korea. Although antimicrobial susceptibility tests are important for appropriate patient management in M. abscessus lung disease, the tests have never been investigated in Korea. Seventy-four isolates of M. abscessus recovered from patient respiratory samples were tested against eight antimicrobial agents following the guidelines set forth by the National Committee for Clinical Laboratory Standards. Of the parenteral antibiotics, amikacin (99%, 73/74) and cefoxitin (99%, 73/74) were active against most isolates. Imipenem (55%, 36/66) and tobramycin (36%, 27/74) had activity against moderate number of isolates. Of the oral antibiotics, clarithromycin (91%, 67/74) was active against the majority of isolates. Moxifloxacin (73%, 54/74) and ciprofloxacin (57%, 42/74) had activity against a moderate number of isolates. Doxycycline was the least active, inhibiting only 7% (5/74) of isolates. In conclusion, the variations in susceptibility within M. abscessus isolates to currently available antimicrobials suggest that the antimicrobial susceptibilities of any clinically significant M. abscessus isolate be needed individually.

The Effect of Hyperglycemia Induced by Oral Glucose Loading on Coronary Flow Reserve

BACKGROUND AND OBJECTIVES: Patients with chronic diabetes mellitus (DM) have an increased risk of cardiac dysfunction and mortality. There is some evidence that suggests acute hyperglycemia may cause vascular dysfunction. However, it is unknown whether acute, short-term hyperglycemia affects coronary microcirculation function in healthy subjects. The present study was undertaken to explore this issue. SUBJECTS AND METHODS: We evaluated 20 healthy males who had no history of DM or impaired glucose tolerance, ranging in age from 23 to 36 years (25.9+/-3.3 years). We checked blood sugar, 12-lead electrocardiography, pulse wave velocity, and coronary flow reserve using echocardiography during fasting, and 30, 60, 90, and 120 minutes after ingestion of 75 g of glucose orally. RESULTS: Non-significant prolongation of the QTc dispersion was observed after the 75 g glucose loading. No significant difference in the pulse wave velocity of the carotid-to-femoral artery, carotid-to-radial artery, or femoral-to-dorsalis pedis artery was observed after the 75 g glucose loading. There was a significant reduction in the coronary flow reserve at 60 (4.06+/-0.75 vs. 3.54+/-0.82, p=0.021) and 90 minutes (4.06+/-0.75 vs. 3.59+/-0.63, p=0.021) after the 75 g glucose loading compared to that on fasting. CONCLUSION: The results of this study suggest that acute exposure to high circulating glucose levels does not affect heterogeneity of the ventricular repolarization or arterial stiffness, but it does reduce the coronary flow reserve in healthy young men.

Effect of Additional Statin Therapy on Endothelial Function and Prognosis in Patients With Vasospastic Angina

BACKGROUND AND OBJECTIVES: Vasospastic angina is correlated with endothelial dysfunction. We compared endothelial function using flow-mediated vasodilatation (FMD) and circulating endothelial progenitor cells (EPCs) between patients with vasospasm and those without vasospasm and studied the effect of statin therapy on the changes of FMD and EPCs in vasospastic angina patients. SUBJECTS AND METHODS: In 133 patients who underwent an ergonovine provocation test, endothelial function was compared based on the presence or absence of spasm. The patients with coronary artery spasm (74 patients) were randomly assigned to either the 10 mg rosuvastatin group or the placebo group. We compared changes in the FMD and EPCs level for 6 months from the time of enrollment between the two groups. RESULTS: The incidence of cigarette smokers was higher in vasospastic angina patients than in those without spasm (p<0.001). The number of EPCs (68.6+/-36.1 vs. 103.7+/-39.3/200 microliter, p<0.001) and the FMD (7.1+/-4.5 vs. 8.6+/-3.6%, p=0.044) were significantly lower in patients with coronary artery spasm than in those without spasm. After 6 months of rosuvastatin treatment, the number of CD45(low)CD34(+) vascular endothelial growth factor receptor 2 (VEGFR2)(+) cells, which was defined as EPCs, increased significantly from 73.1+/-37.8/200 microliter to 99.1+/-37.8/200 microliter (p=0.002). The FMD was significantly ameliorated from 7.3+/-4.1 to 9.3+/-3.4% after 6 months of treatment (p<0.001). The FMD was correlated with the EPCs count before treatment (r=0.229, p=0.049) and after 6 months of treatment (r=0.268, p=0.020). CONCLUSION: The number of circulating EPCs and the FMD were reduced in vasospastic angina, and statin treatment increased the number of EPCs and the FMD. The EPCs level was correlated with the FMD.

Integrated Cell Culture-PCR Detection of Enteroviruses and Reoviruses in Water Sources in Gyeonggi-do

The integrated cell culture-PCR (ICC-PCR) method has been suggested as an improved method for detection of viruses in water environments. We tested 57 source waters including finished water samples in Gyeonggi-do for enteric viral contamination using total culturable virus assay (TCVA) using BGMK cells and ICC-PCR. Nineteen of the 57 source water samples (33.3%) exhibited the cytopathic effect (CPE) on BGMK cells and no finished water did exhibited CPE. Nineteen samples (33.3%) of the 57 were positive for reoviruses. For the enteroviruses, only 3 samples (5.3%) of the 57 samples showed positive results. By using ICC-PCR method, 202 flasks from source water samples were positive for enteroviruses and reoviruses. Three samples from source water were positive for both viruses. However, any flasks tested was not co-infected with two types of viruses. While the enteric viral frequencies in TCVA and ICC-PCR were similar, the viral frequency for reoviruses at first passage in two type of method was higher in ICC-PCR (94.7%) than TCVA (56.9%).

Changes of C-reactive Protein are Associated With Myocardial Injury After Successful Percutaneous Coronary Intervention

BACKGROUND AND OBJECTIVES: Myocardial injury after percutaneous coronary intervention (PCI) occurs frequently and it is associated with an adverse clinical outcome. Mechanical factors have been implicated in this complication and the role of inflammation has not yet been clearly determined. We evaluated the effect of an inflammatory response during PCI on periprocedural myocardial injury. SUBJECTS AND METHODS: We prospectively studied 231 patients (mean age: 62.8+/-10.6 years, males: 60.6%) who underwent elective coronary stenting. For the exclusion of mechanical injury to the myocardium, we excluded those patients who developed complications during PCI. Blood samples for measuring the high sensitivity C-reactive protein (hsCRP) and troponin T (TnT) were obtained before the procedure and at 6 hours and 24 hours after PCI. The inflammatory response to PCI was calculated as the difference between the peak postprocedural hsCRP level and the preprocedural hsCRP level (delta CRP). We divided the patients according to the median value of delta CRP: Group I or =2.2 mg/dL. RESULTS: Postprocedural TnT elevation was were observed in 72 (31.2%) patients. The baseline clinical and angiographic characteristics were not difference between the two groups. The incidence of any TnT elevations was higher in the Group II than that in Group I (19.8% vs 42.6%, respectively, p<0.001). The incidences of TnT levels over 3 times the upper normal limit and 5 times the upper normal limit were also higher in Group II than in Group I (11.2% vs 21.7%, respectively, p=0.031, for a TnT level 3 times the upper normal limit, and 6.0% vs 13.9%, respectively, for a TnT level 5 times the upper normal limit). Multivariate analysis revealed that postprocedural hsCRP elevation and complex lesion were the significant independent predictors of postprocedural TnT elevation. CONCLUSION: Elevated hsCRP levels were associated with a higher risk of postprocedural troponin elevation in patients undergoing uncomplicated PCI. These results emphasized the role of inflammation in the pathogenesis of periprocedural myocardial injury.