Coronary Sinus Metabolite 12,13-diHOME Is a Novel Biomarker for Left Atrial Remodeling in Patients With Atrial Fibrillation.

BACKGROUND: 12,13-dihydroxy-9Z-octadecenoic acid (12,13-diHOME) has shown potential in protecting against heart disease, but its relationship with atrial fibrillation (AF) remains unknown. METHODS: Coronary sinus (CS) and femoral vein blood samplings were synchronously collected from AF and non-AF subjects (paroxysmal supraventricular tachycardia or idiopathic premature ventricular complexes) who underwent catheter ablation. First, untargeted metabolomic profiling was performed in a discovery cohort (including 12 AF and 12 non-AF subjects) to identify the most promising CS or femoral vein metabolite. Then, the selected metabolite was further measured in a validation cohort (including 119 AF and 103 non-AF subjects) to confirm its relationship with left atrium remodeling and 1-year postablation recurrence of AF. Finally, the biological function of the selected metabolite was validated in a rapid-paced cultured HL-1 atrial cardiomyocytes model. RESULTS: Metabolomic analysis identified CS 12,13-diHOME as the most pronounced change metabolite correlated with left atrium remodeling in the discovery cohort. In the validation cohort, CS 12,13-diHOME was significantly lower in patients with AF than non-AF controls (84.32±20.13 versus 96.24±23.56 pg/mL; P<0.01), and associated with worse structural, functional, and electrical remodeling of left atrium. Multivariable regression analyses further demonstrated that decreased CS 12,13-diHOME was an independent predictor of 1-year postablation recurrence of AF (odds ratio, 0.754 [95% CI, 0.648-0.920]; P=0.005). Biological function validations showed that 12,13-diHOME treatment significantly protect the cell viability, improved the expression of MHC (myosin heavy chain) and Cav1.2 (L-type calcium channel α1c), and attenuated mitochondrial damage in the rapid-paced cultured HL-1 cardiomyocytes model. CONCLUSIONS: CS metabolite 12,13-diHOME is decreased in patients with AF and can serve as a novel biomarker for left atrium remodeling.

The adipose-neural axis is involved in epicardial adipose tissue-related cardiac arrhythmias.

Dysfunction of the sympathetic nervous system and increased epicardial adipose tissue (EAT) have been independently associated with the occurrence of cardiac arrhythmia. However, their exact roles in triggering arrhythmia remain elusive. Here, using an in vitro coculture system with sympathetic neurons, cardiomyocytes, and adipocytes, we show that adipocyte-derived leptin activates sympathetic neurons and increases the release of neuropeptide Y (NPY), which in turn triggers arrhythmia in cardiomyocytes by interacting with the Y1 receptor (Y1R) and subsequently enhancing the activity of the Na+/Ca2+ exchanger (NCX) and calcium/calmodulin-dependent protein kinase II (CaMKII). The arrhythmic phenotype can be partially blocked by a leptin neutralizing antibody or an inhibitor of Y1R, NCX, or CaMKII. Moreover, increased EAT thickness and leptin/NPY blood levels are detected in atrial fibrillation patients compared with the control group. Our study provides robust evidence that the adipose-neural axis contributes to arrhythmogenesis and represents a potential target for treating arrhythmia.

Redistribution of adipose tissue is associated with left atrial remodeling and dysfunction in patients with atrial fibrillation.

Objective: Adipose tissue is recognized as a crucial regulator of atrial fibrillation (AF). However, the effect of epicardial adipose tissue (EAT) on the pathophysiology of AF might be different from that of other adipose tissues. The purpose of this study was to explore the distribution features of different adipose tissues in AF patients and their relationships with left atrial (LA) remodeling and function. Methods: A total of 205 participants (including 112 AF and 93 non-AF patients) were recruited. Color doppler ultrasound was used to measure the thickness of subcutaneous, extraperitoneal, and intra-abdominal adipose tissue. Cardiac CT scan was performed to measure the mean thickness of EAT surrounding the whole heart (total-EAT) and specific regions, including left atrium (LA-EAT), left ventricle, right ventricle, interventricular groove, and atrioventricular groove. LA anatomical remodeling and function were measured by echocardiography, while electrical remodeling was evaluated by P-wave duration and dispersion using Electrocardiography (obtained after cardioversion or ablation in AF patients). Relationship between the thickness of different adipose tissues and LA remodeling and function was analyzed. Results: The thickness of subcutaneous, extraperitoneal, and intra-abdominal adipose tissue was similar between AF and non-AF patients, and had no or only weak association with LA remodeling and dysfunction. However, compared to non-AF participants, total-EAT thickness significantly increased in both paroxysmal and persistent AF patients (non-AF vs. paroxysmal AF vs. persistent AF: 6.31 ± 0.63 mm vs. 6.76 ± 0.79 mm vs. 7.01 ± 1.18 mm, P < 0.001), which was positively correlated with the LA size and P-wave duration and dispersion, and negatively correlated with LA ejection fraction and peak strain rate. More interestingly, EAT thickness in AF patients did not increase uniformly in different regions of the heart. Compared to EAT surrounding the other regions, LA-EAT was found to accumulate more greatly, and had a closer relationship to LA remodeling and dysfunction. Multivariate logistic regression analysis also showed that LA-EAT was significantly correlated with the presence of AF (OR = 4.781; 95% CI 2.589-8.831, P < 0.001). Conclusion: Rather than other adipose tissues, accumulation and redistribution of EAT, especially surrounding the LA, is associated with LA remodeling and dysfunction in AF patients.

The feasibility and safety of a simple method for coronary sinus blood sampling during catheter ablation of arrhythmias.

Background: Coronary sinus (CS) blood sampling gives an insight into the localized pathophysiology of heart diseases. However, additional specifically-designed or modified catheters were needed in most previous studies, making the convenience of clinical application unsatisfactory. This study aimed to introduce a simple method for CS blood sampling without using additional catheters during catheter ablation (CA) of arrhythmias, and to investigate its feasibility and safety. Methods: A total of 119 patients undergoing CA were prospectively enrolled, including 25 with paroxysmal supraventricular tachycardia (PSVT), 30 with premature ventricular complexes (PVC), and 64 with atrial fibrillation (AF). Cannulation and sampling of CS was performed via the femoral vein using a conventional 8F SR0TM or 8.5F SL1TM introducer sheath (St. Jude Medical) guided by a 6F steerable diagnostic catheter (St. Jude Medical). The success rate and any suspicious complications were recorded. Untargeted liquid chromatograph-mass spectrometer (LC-MS)-based metabonomics of CS samples versus peripheral venous samples were also performed. Results: CS blood samples were successfully collected from 114 patients, with an overall success rate of 95.8%. Among patients with different arrhythmias, the success rates were similar, with 96.0% in PSVT, 96.7% in PVC, and 95.3% in AF (P=0.223). Adverse events occurred in four (3.4%) patients, including two patients with occasional atrial ectopic beats without causing any discomfort, and two patients with new-onset paroxysmal AF lasting for about 2 min. No serious complications were noted. Metabonomics analysis showed that CS samples provided a number of different metabolites (93 in PVST, 217 in PVC, and 109 in AF) versus peripheral samples. Conclusions: Our method for CS blood sampling during CA is feasible and safe, and can provide useful cardiometabolic information that is significantly different from a peripheral sample.

Renin-Angiotensin System Inhibitors for the Prevention of Atrial Fibrillation Recurrence After Ablation　- A Meta-Analysis.

BACKGROUND: Atrial fibrillation (AF) recurrence remains a tricky problem in patients undergoing ablation. This meta-analysis aimed to summarize the current literature to clarify whether renin-angiotensin system inhibitors (RASIs) prevent AF recurrence after ablation.Methods and Results:Relevant studies were searched on Pubmed and EMBASE through December 2019. Pooled relative risk (RR) of AF recurrence was calculated. Subgroup analyses according to study design, race, and follow-up duration were further performed. A total of 15 studies examining 4,300 patients were included, with 3 randomized controlled trials and 12 cohort studies. Overall analysis showed that RASIs significantly reduced AF recurrence after ablation (RR=0.83; 95% confidence interval (CI) 0.70-0.98, P=0.028; I2=68.9%). Subgroup analysis further indicated that positive results were found in randomized controlled trials (RR=0.51, 95% CI 0.37-0.70, P<0.001; I2=4%), studies conducted in Asia (RR=0.59, 95% CI 0.46-0.76, P<0.001; I2=30.7%), and studies with follow-up duration ≥1 year (RR=0.82, 95% CI 0.70-0.95, P=0.01; I2=59.1%); negative results were found in cohort studies, studies conducted in Europe or the USA, and studies with follow-up duration <1 year. CONCLUSIONS: RASIs can potentially prevent AF recurrence after ablation under selected conditions. However, more studies are required to confirm this finding due to the variation in current evidence.

Ginsenoside Rb1 reduces H2O2­induced HUVEC dysfunction by stimulating the sirtuin­1/AMP­activated protein kinase pathway.

Endothelial dysfunction and senescence are closely associated with cardiovascular diseases including atherosclerosis and hypertension. Ginsenoside Rb1 (Rb1), the major active constituent of ginseng, has been investigated intensively because of its anti­obesity and anti­inflammatory effects. In a previous study, hydrogen peroxide (H2O2) was applied to induce human umbilical vein endothelial cell (HUVEC) aging. It was demonstrated that Sirtuin­1 (SIRT1) was activated by Rb1 to protect HUVECs from H2O2­induced senescence. However, the mechanisms are not fully understood. The present study examined the role of AMP­activated protein kinase (AMPK), an energy sensor of cellular metabolism, in the signaling pathway of SIRT1 during H2O2­stimulated HUVEC aging. It was identified that Rb1 restored the H2O2­induced reduction of SIRT1 expression, which was consistent with our previous study, together with the activation of AMPK phosphorylation. Using compound C, an AMPK inhibitor, the role of AMPK in the protective effect of Rb1 against H2O2­induced HUVEC senescence was examined. It was identified that the induction of phosphorylated AMPK by Rb1 markedly increased endothelial nitric oxide synthase expression and nitric oxide production, and suppressed PAI­1 expression, which were abrogated in HUVECs pretreated with compound C. Further experiments demonstrated that nicotinamide, a SIRT1 inhibitor, downregulated the phosphorylation of AMPK and reduced the protective effects of Rb1 against H2O2­induced endothelial aging. Taken together, these results provide new insights into the possible molecular mechanisms by which Rb1 protects against H2O2­induced HUVEC senescence via the SIRT1/AMPK pathway.

Predictive value of P wave terminal force in lead V1 for atrial fibrillation: A meta-analysis.

BACKGROUND: Several studies have explored the association between P wave terminal force in lead V1 (PTFV1) and risk of atrial fibrillation (AF) occurrence, but the results were controversial. This meta-analysis aimed to examine whether abnormal PTFV1 could predict AF occurrence. METHODS: We searched PubMed, Embase, and Cochrane Library databases for articles published before August 25, 2018. Pooled odds ratios (ORs) of AF occurrence were calculated using random-effects models to explore the significance of PTFV1. RESULTS: A total of 12 studies examining 51,372 participants were included, with 9 studies analyzing PTFV1 as a categorical variable and 4 studies analyzing PTFV1 as a continuous variable. As a categorical variable, abnormal PTFV1 (>0.04 mm s) was significantly associated with AF occurrence with a pooled OR of 1.39 (95% confidence interval [CI] 1.08-1.79, p = .01). Subgroup analysis found that ORs of studies in hemodialysis patients (OR = 4.89, 95% CI 2.54-9.90, p < .001) and acute ischemic stroke patients (OR = 1.60, 95% CI 1.14-2.25, p = .007) were higher than general population (OR = 1.15, 95% CI 1.03-1.29, p = .01). Studies from Europe (OR = 1.05, 95% CI 0.91-1.20, p = .51) yielded lower OR of endpoints compared with Asia (OR = 1.89, 95% CI 1.38-2.60, p < .001) and United States (OR = 1.43, 95% CI 1.19-1.72, p < .001). As a continuous variable, PTFV1 was also significantly associated with AF occurrence with a polled OR per 1 standard deviation (SD) change of 1.27 (95% CI 1.02-1.59, p = .03). CONCLUSIONS: PTFV1 was significantly associated with the risk of AF and was considered to be a good predictor of AF occurrence in population with or without cardiovascular diseases.

Beneficial effect of ER stress preconditioning in protection against FFA-induced adipocyte inflammation via XBP1 in 3T3-L1 adipocytes.

Adipose tissue inflammation is closely associated with the development of obesity and insulin resistance. Free fatty acids (FFAs) are a major inducer of obesity-related insulin resistance. Previously, we reported that endoplasmic reticulum (ER) stress potentially mediated retinal inflammation in diabetic retinopathy. The unfolded protein response (UPR) protects cells against damage induced by oxidative stress. X-box binding protein 1 (XBP1) plays a major role in protecting cells by modulating the UPR. However, the link between ER stress and adipocyte inflammation has been poorly investigated. In the present study, we found that pretreatment of 3T3-L1 adipocytes with a low dose of ER stress inducer tunicamycin inhibited FFA-induced upregulated expression of inflammatory cytokines. In addition, FFAs induced phosphorylation of the p65 subunit of NF-κB was largely inhibited by pretreatment with tunicamycin in 3T3-L1 adipocytes. Knockdown of XBP1 by siRNA markedly mitigated the protective effects of preconditioning against inflammation. Conversely, overexpression of XBP1 alleviated FFA-induced phosphorylation of IκB-α, IKKα/ß, and NF-κB, which was accompanied by decreased inflammatory cytokine expression. Collectively, these results imply a beneficial role of ER stress preconditioning in protecting against FFA-induced 3T3-L1 adipocyte inflammation, which is likely mediated through inhibition of the IKK/NF-κB pathway via XBP1.

Impact of HbA1c variability on subclinical left ventricular remodeling and dysfunction in patients with type 2 diabetes mellitus.

BACKGROUND: Glycemic instability confers a risk of poor prognosis in patients with type 2 diabetes mellitus (T2DM). This study aimed to investigate whether HbA1c variability provided additional value over mean HbA1c for predicting subclinical left ventricular remodeling and dysfunction in T2DM patients. METHODS: A total of 466 T2DM patients with normal cardiac structure and function were recruited and prospectively followed up for a median of 4.7 y. HbA1c was measured quarterly. The intrapersonal mean and standard deviation (SD) of HbA1c measurements were calculated, and SD-HbA1c was considered as a measure of HbA1c variability. All participants underwent transthoracic echocardiography at baseline and after follow-up. RESULTS: In multivariable regression analyses, SD-HbA1c was independently associated with annualized changes in left ventricular end diastolic diameter, interventricular septum, left ventricular posterior wall, left ventricular mass index, left ventricular ejection fraction, E/e' ratio, and E/A ratio (P < 0.001). Subgroup analysis based on mean HbA1c levels (<7.0%, 7.0-7.5%, and ≥7.5%) further confirmed that SD-HbA1c was associated with most of the above parameters regardless of mean HbA1c levels. CONCLUSION: This study indicates that HbA1c variability adds to the mean value in predicting subclinical left ventricular remodeling and dysfunction in T2DM patients.

Ginsenoside Rb1 inhibits free fatty acids­induced oxidative stress and inflammation in 3T3­L1 adipocytes.

Free fatty acids (FFAs) increase in visceral fat and are inferred to be one of the underlying inducers of adipose tissue inflammation. In our previous study, it was demonstrated that ginsenoside Rb1 stimulates endothelial nitric oxide synthase (eNOS) and Sirtuin 1 to protect against endothelial cell senescence. In the present study, 3T3­L1 adipocytes were exposed to 0.5 mM FFAs with or without Rb1 (10­40 µM). Monocyte chemotactic protein­1 (MCP­1) and interleukin­6 (IL­6) secretion was measured using ELISA. Tumor necrosis factor­α (TNF­α) expression and nuclear factor­κB (NF­κB) p65 phosphorylation were detected using western blot analysis. Oxidative stress was determined via measuring intracellular reactive oxygen species (ROS) and nitric oxide (NO) production. The results demonstrated that MCP­1 and IL­6 secretion, as well as TNF­α expression, were significantly increased following FFA treatment, which was attenuated by Rb1 in a dose­dependent manner. Furthermore, Rb1 attenuated FFA­induced NF­κB phosphorylation, suggesting that the inhibitory effect of Rb1 on inflammatory cytokines was partially mediated through blockade of NF­κB phosphorylation. Further experiments demonstrated that Rb1 ameliorated FFA­induced ROS generation and NO reduction through upregulation of superoxide dismutase 2 and eNOS expression. Taken together, these results demonstrate proinflammatory and pro­oxidant effects of FFA on 3T3­L1 adipocytes, which are effectively ameliorated by Rb1. Suppression of inflammatory responses and oxidative stress may be a novel mechanism for attenuating the effect of Rb1 on adipocyte dysfunction.

The prognostic value of exercise-induced ventricular arrhythmias in patients with and without coronary artery disease: A meta-analysis.

BACKGROUND: Significance of exercise-induced ventricular arrhythmias (EIVAs) is controversial. This meta-analysis aimed to determine the prognostic value of EIVAs in patients with and without coronary artery disease (CAD). METHODS: Relevant studies were searched on Pubmed though December, 2015. Pooled odds ratio (OR) of endpoints (all-cause death, cardiac death or cardiac events) for all included studies was calculated at first to explore the significance of EVIAs in unselected population. Then, sensitivity analysis based on CAD status of population was performed to determine ORs of endpoints in CAD population, non-CAD population and mixed population, respectively. RESULTS: A total of 14 studies examining 23,002 patients were included, with 5 studies involved CAD population, 4 involved non-CAD population, and 5 involved mixed population (%CAD ranged from 51.2% to 76.8%). EIVAs in unselected population were associated with a pooled OR of 1.626 (95%CI 1.334 to 1.983, p<0.001) of endpoints when compared with those without EIVAs. Sensitivity analysis further indicated that pooled ORs of endpoints were 1.395 (95%CI 1.061 to 1.833, p=0.017) in CAD population, 1.933 (95%CI 1.567 to 2.384, p<0.001) in non-CAD population, and 1.402 (95%CI 1.198 to 1.640, p<0.001) in mixed population. Heterogeneous among studies was identified. Meta-regression analysis found that study quality, mean follow-up period, percentage of lost, percentage of diabetes were associated with ORs of endpoints. CONCLUSIONS: EIVAs were associated with increased risk of worse outcomes, no matter the patients had CAD or not. However, more studies are required to confirm this finding due to the variation of current evidences.

Preprocedure and Postprocedure Predictive Values of Serum ß2-Microglobulin for Contrast-Induced Nephropathy in Patients Undergoing Coronary Computed Tomography Angiography: A Comparison With Creatinine-Based Parameters and Cystatin C.

OBJECTIVE: This study aimed to investigate the values of serum ß2-microglobulin to predict contrast-induced nephropathy (CIN) before and early after coronary computed tomography angiography (CCTA), comparing with creatinine-based parameters and cystatin C. METHODS: A total of 424 patients were enrolled. Serum ß2-microglobulin, cystatin C, and creatinine were measured at 0, 24, and 48 hours of CCTA. Contrast-induced nephropathy was defined as an elevation of serum creatinine level by 25% or higher or 0.5 mg/dL or greater from baseline within 48 hours. The estimated glomerular filtration rate (eGFR) was calculated by the Modification of Diet in Renal Disease study equation. Receiver operating characteristic curves and multivariate logistic regression analysis were used to detect the efficiency of biomarkers in predicting CIN. RESULTS: Fifty-two subjects (12.26%) developed CIN. Before CCTA, CIN was predicted by both baseline ß2-microglobulin (area under the receiver operating characteristic curve [AUC], 0.791; P < 0.001) and cystatin C (AUC, 0.781; P < 0.001), whereas creatinine and eGFR were not predictive. After CCTA, CIN was predicted by both the absolute post-CCTA levels of ß2-microglobulin, cystatin C, creatinine, and eGFR (AUC, 0.842 vs 0.961 vs 0.691 vs 0.688 at 24 hours, P < 0.001; and 0.937 vs 1.000 vs 0.908 vs 0.898 at 48 hours, P < 0.001) and their relative changes (Δ) to baseline (AUC, 0.677 vs 0.846 vs 0.850 vs 0.844 at 24 hours, P < 0.001; and 0.731 vs 0.968 vs 0.984 vs 0.966 at 48 hours, P < 0.001). Multivariate regression analysis confirmed that baseline ß2-microglobulin (odds ratio, 2.137; 95% confidence interval, 1.805-3.109; P < 0.001) and cystatin C (odds ratio, 1.873; 95% confidence interval, 1.667-2.341; P = 0.003) were independent predictors for CIN. CONCLUSIONS: Serum ß2-microglobulin, with values superior to creatinine-based parameters and similar with cystatin C, was a useful biomarker for the prediction of CIN at pre-CCTA and early post-CCTA.

Use of concept maps to promote electrocardiogram diagnosis learning in undergraduate medical students.

Concept mapping is an effective method in teaching and learning, however this strategy has not been evaluated among electrocardiogram (ECG) diagnosis learning. This study explored the use of concept maps to assist ECG study, and sought to analyze whether this method could improve undergraduate students' ECG interpretation skills. There were 126 undergraduate medical students who were randomly selected and assigned to two groups, group A (n = 63) and group B (n = 63). Group A was taught to use concept maps to learn ECG diagnosis, while group B was taught by traditional methods. After the course, all of the students were assessed by having an ECG diagnostic test. Quantitative data which comprised test score and ECG features completion index was compared by using the unpaired Student's t-test between the two groups. Further, a feedback questionnaire on concept maps used was also completed by group A, comments were evaluated by a five-point Likert scale. The test scores of ECGs interpretation was 7.36 ± 1.23 in Group A and 6.12 ± 1.39 in Group B. A significant advantage (P = 0.018) of concept maps was observed in ECG interpretation accuracy. No difference in the average ECG features completion index was observed between Group A (66.75 ± 15.35%) and Group B (62.93 ± 13.17%). According qualitative analysis, majority of students accepted concept maps as a helpful tool. Difficult to learn at the beginning and time consuming are the two problems in using this method, nevertheless most of the students indicated to continue using it. Concept maps could be a useful pedagogical tool in enhancing undergraduate medical students' ECG interpretation skills. Furthermore, students indicated a positive attitude to it, and perceived it as a resource for learning.

Successful diagnosis of hyperpyrexia induced by isoniazid in a child with suspected extra-pulmonary tuberculosis.

A 9-year-old boy received a rifampicin-isoniazid-ethambutol regimen for suspected extra-pulmonary tuberculosis, and glucurolactone and vitamin B6 to provide liver protection and decrease neurotoxicity associated with isoniazid. Baseline serum aminotransferase and total bilirubin levels were within normal limits before anti-tubercular treatment. After 4 days of treatment, the patient's body temperature increased (from 38.0°C to 40.1°C) and on the 11th day of treatment, serum chemistry results showed 400 U/L aspartate transaminase, 535 U/L alanine aminotransferase and 76.8 µmol/L total bile acid, which likely indicated drug-induced hepatic injury. After discontinuing isoniazid or administering anti-tubercular therapy without isoniazid, hyperpyrexia gradually resolved; hyperpyrexia reappeared following rechallenge with isoniazid. The patient's liver function returned to normal after symptomatic treatment. Thus, hyperpyrexia that accompanied hepatic injury was considered to be related to isoniazid. This case indicated that hyperpyrexia could also appear during anti-tubercular treatment owing to its hepatotoxicity.

Advanced glycation end products upregulate angiopoietin-like protein 4 expression by activating the renin-angiotensin system in endothelial cells.

The aim of the present study was to investigate the effects of advanced glycation end products (AGEs) on the expression of angiopoietin-like protein 4 (ANGPTL4) and the mechanisms of the effects in endothelial cells. Endothelial cells were incubated with various concentrations of AGEs for 24 h and the expression of ANGPTL4 was detected by quantitative polymerase chain reaction and western blot analysis. The concentration of angiotensin II (Ang II) in conditioned media and cell lysates was measured by enzyme-linked immunosorbent assays. Fluorescein isothiocyanate-labeled dextran filtration assays and transendothelial electrical resistance were performed to evaluate endothelial permeability. AGEs (80 µg/ml) increased the expression of ANGPTL4 and the levels of Ang II (P<0.05). Incubation with AGEs also resulted in a significant increase in endothelial permeability (P<0.05). However, pretreatment with the Ang II receptor blocker losartan (10-5 M) reduced the effects of AGEs (P<0.05). AGEs upregulated the expression of ANGPTL4 by activating a local renin-angiotensin system in endothelial cells. This may be a new mechanism by which AGEs increase endothelial permeability.

A case of chronic hepatitis C patient of myocardial ischemia accompanied with interstitial pneumonia induced by pegylated interferon alpha-2a.

After 3 months of combination treatment using interferon α-2a and Ribavirin, a case of 59-year-old female patient with chronic viral hepatitis C demonstrated symptoms such as headache, dizziness accompanied by nausea, vomiting, dry cough, breathing difficulty, and shortness of breath. Dynamic electrocardiogram showed occasional atrial premature beats, paroxysmal tachycardia, and abnormal ST-T (T wave inversion and prolongation of the QT interval). Ambulatory blood pressure indicated that mean blood pressure was elevated than before. Myocardial radionuclide scan showed focal myocardial ischemia in left ventricular inferior wall. Pulmonary function tests showed that pulmonary diffusion function was decreased, indicating the possibility of interstitial pneumonia. The patient had no history of coronary heart disease or chest X-ray abnormalities before medication, but had hypertensive medical history for 8 years with good blood pressure control. After withdrawal of antiviral drugs, symptoms such as dry cough, breathing difficulty and T wave inversion were gradually relieved. This case indicated that myocardial ischemia and pulmonary lesions were associated with the application of pegylated interferon α-2a.

Advanced glycation end-products reduce podocyte adhesion by activating the renin-angiotensin system and increasing integrin-linked kinase.

The aim of this study was to investigate the effects of advanced glycation end-products (AGEs) on podocyte adhesion and the underlying mechanisms. Immortalized mouse podocytes were exposed to various conditions and podocyte adhesion was evaluated using a hexosaminidase assay. The expression levels of integrin-linked kinase (ILK) were measured by quantitative polymerase chain reaction (qPCR) and western blotting. Treatment with AGEs resulted in a significant, concentration-dependent reduction in podocyte adhesion (P<0.05) and an incremental rise in ILK expression up to a maximum of 100%. Pretreatment with losartan significantly prevented the upregulation of ILK and attenuated the loss of podocyte adhesion observed in podocytes exposed to AGEs (P<0.05). However, the adhesion of losartan-treated podocytes remained lower than that of the podocytes exposed to bovine serum albumin. The results indicate that AGEs reduce podocyte adhesion via the upregulation of ILK expression, which occurs partly through activation of the renin-angiotensin system in podocytes.

Association of serum gamma-glutamyltransferase with arterial stiffness in established coronary artery disease.

Serum gamma-glutamyltransferase (GGT) has been reported to predict vascular risk. We enrolled 978 patients (507 men and 471 women) with established coronary artery disease (CAD). The GGT, brachial-ankle pulse wave velocity ([baPWV] to assess arterial stiffness), and conventional risk factors were evaluated. The means of baPWV tend to increase in both genders according to GGT tertiles. Body mass index, GGT, logarithmical (systolic blood pressure [LnSBP]), uric acid (UA), total bilirubin, Ln (cholinesterase), and Ln (total cholesterol) were correlated with baPWV in men in a multivariate model. However, only GGT, LnSBP, UA, and Ln (high-density lipoprotein cholesterol) were correlated with baPWV in women. The GGT was a significant determinant for increased baPWV both in men (ß = 0.017; P < .001) and in women (ß = 0.015; P < .001). In conclusion, GGT was independently associated with increased arterial stiffness both in men and in women with established CAD.