High pressure conditions promote the proliferation of rat cultured mesangial cells in vitro

AbstractGlomerular capillary pressure is involved in the development of chronic renal failure and has at least two effects on mesangial cells: transmembrane hydrostatic pressure and stretch. To clarify whether pure hydrostatic pressure itself affects the proliferation of cultured rat mesangial cells, we compared the cell number under atmospheric pressure condition with high pressure condition. At 24 and 48h with 0.5% serum, cell number was significantly higher under high pressure condition than under atmospheric pressure condition. At 48h, cell number under high pressure condition was increased in a pressure-dependent manner. Furthermore, flow cytometric assay indicated that pressure-load could promote DNA synthesis rate at S phase and enhance G1/S progression induced by low concentration of serum (0.5%). These results suggest that pure hydrostatic pressure itself can promote the proliferation of cultured rat mesangial cells by advancing cell cycle progression in vitro

Tissue Characterization of Coronary Plaque by Using Fractal Analysis-based Features of IVUS RF-signal

We propose a precise tissue characterization method of coronary plaque by using fractal analysis-based features which are obtained from radiofrequency (RF) signal employing intravascular ultrasound (IVUS) method. The IVUS method is used for the diagnosis of the acute coronary syndromes (ACS). In the proposed method, the fact that the RF signal reflects the complexity of the structure of tissue is used. The effectiveness of the proposed method is verified through a series of experiments by using IVUS RF signals obtained from a rabbit and a human patient

Efficacy of N-acetylcysteine and aminophylline in preventing contrast-induced nephropathy

SummaryBackgroundContrast-induced nephropathy (CIN) is one of the important complications of coronary angiography (CAG) and percutaneous coronary intervention (PCI), especially in patients with chronic kidney disease (CKD). Prophylactic administration of N-acetylcysteine (NAC) and aminophylline has been reported to be effective in some trials, but the results still remain controversial. We investigated the efficacy of NAC or aminophylline in preventing CIN.Methods and resultsForty-five consecutive patients undergoing CAG and/or PCI were randomly assigned to receive hydration and NAC (704mg orally twice daily; NAC group, n=15), hydration and aminophylline (250mg intraveneously 30min before CAG and/or PCI; aminophylline group, n=15), or hydration alone (control group, n=15). We compared serum creatinine (SCr), creatinine clearance (Ccr), blood beta-2 microglobulin, and urinary beta-2 microglobulin levels at baseline and 48h after CAG and/or PCI. In the NAC group, SCr decreased from 1.00±0.36 to 0.67±0.16mg/dl (p<0.01), and Ccr significantly increased from 62.4±15.6 to 80.4±8.39ml/min (p<0.01). In the aminophylline group, SCr and Ccr were unchanged. In the control group, SCr significantly increased from 0.94±0.21 to 1.28±0.21mg/dl (p<0.01), and Ccr significantly decreased from 63.7±16.1 to 46.1±10.6ml/min (p<0.01) after CAG and/or PCI. In the NAC group, mean blood beta-2 microglobulin significantly decreased from 2.38±0.58 to 1.71±0.38mg/dl (p<0.01), and in the aminophylline group, mean urinary beta-2 microglobulin concentration significantly decreased from 337±31.0 to 239±34μg/ml (p<0.01).ConclusionsThese results suggest that both prophylactic NAC and aminophylline administration are effective in preventing CIN, but not with hydration alone. It appears that the two compounds work in different ways against CIN

Proteasome-dependent decrease in Akt by growth factors in vascular smooth muscle cells

AbstractAkt is activated by growth factors to regulate various aspects of vascular smooth muscle cell function. Platelet-derived growth factor (PDGF) and insulin-like growth factor-1 activated Akt in vascular smooth muscle cells with a rapid reduction of total Akt protein that lasted for several hours. The downregulation of Akt required phosphatidylinositol 3-kinase activity, but not intrinsic Akt activity. The downregulation of Akt was abrogated by MG-132, a proteasome inhibitor, but not by inhibitors of calpain or cathepsins. Akt was found in ubiquitin immune complex after PDGF treatment. Proteasome-dependent degradation of Akt may provide a counter-regulatory mechanism against overactivation of Akt

Phosphorylation of proteins and apoptosis induced by c-Jun N-terminal kinase1 activation in rat cardiomyocytes by H2O2 stimulation

AbstractCytokines and various cellular stresses are known to activate c-Jun N-terminal kinase-1 (JNK1), which is involved in physiological function. Here, we investigate the activation of JNK1 by oxidative stress in H9c2 cells derived from rat cardiomyocytes. H2O2 (100 μM) significantly induces the tyrosine phosphorylation of JNK1 with a peak 25 min after the stimulation. The amount of JNK1 protein remains almost constant during stimulation. Immunocytochemical observation shows that JNK1 staining in the nucleus is enhanced after H2O2 stimulation. To clarify the physiological role of JNK1 activation under these conditions, we transfected antisense JNK1 DNA into H9c2 cells. The antisense DNA (2 μM) inhibits JNK1 expression by 80% as compared with expression in the presence of the sense DNA, and significantly blocks H2O2-induced cell death. Consistent with the decrease in cell number, we detected condensation of the nuclei, a hallmark of apoptosis, 3 h after H2O2 stimulation in the presence of the sense DNA for JNK1. The antisense DNA of JNK1 inhibits the condensation of nuclei by H2O2. Under these conditions, the H2O2-induced phosphorylation of proteins with molecular masses of 55, 72, and 78 kDa is blocked by treatment with the antisense DNA for JNK1 as compared with the sense DNA for JNK1. These findings suggest that JNK1 induces apoptotic cell death in response to H2O2, and that the cell death may be involved in the phosphorylations of 55, 72, and 78 kDa proteins induced by JNK1 activation

High HbA1c levels correlate with reduced plaque regression during statin treatment in patients with stable coronary artery disease: Results of the coronary atherosclerosis study measuring effects of rosuvastatin using intravascular ultrasound in Japanese subjects (COSMOS)

Abstract Background The incidence of cardiac events is higher in patients with diabetes than in people without diabetes. The Coronary Atherosclerosis Study Measuring Effects of Rosuvastatin Using Intravascular Ultrasound in Japanese Subjects (COSMOS) demonstrated significant plaque regression in Japanese patients with chronic coronary disease after 76 weeks of rosuvastatin (2.5 mg once daily, up-titrated to a maximum of 20 mg/day to achieve LDL cholesterol Methods In this subanalysis of COSMOS, we examined the association between HbA1c and plaque regression in 40 patients with HbA1c ≥6.5% (high group) and 86 patients with HbA1c Results In multivariate analyses, HbA1c and plaque volume at baseline were major determinants of plaque regression. LDL cholesterol decreased by 37% and 39% in the high and low groups, respectively, while HDL cholesterol increased by 16% and 22%, respectively. The reduction in plaque volume was significantly (p = 0.04) greater in the low group (from 71.0 ± 39.9 to 64.7 ± 34.7 mm3) than in the high group (from 74.3 ± 34.2 to 71.4 ± 32.3 mm3). Vessel volume increased in the high group but not in the low group (change from baseline: +4.2% vs −0.8%, p = 0.02). Change in plaque volume was significantly correlated with baseline HbA1c. Conclusions Despite similar improvements in lipid levels, plaque regression was less pronounced in patients with high HbA1c levels compared with those with low levels. Tight glucose control during statin therapy may enhance plaque regression in patients with stable coronary disease. Trial registration ClinicalTrials.gov, Identifier NCT00329160</p

What variables were associated with the inducibility of ventricular fibrillation during electrophysiologic stimulation test in patients without apparent organic heart disease?

SummaryObjectiveThe purpose of our study was to determine what variables were associated with ventricular fibrillation (VF) induced during electrophysiological stimulation test in patients without apparent organic heart disease.MethodsOur study evaluated 77 patients (51±15 years) who underwent electrophysiological stimulation test, signal averaging, and Na+ channel-blocker challenge test (pilsicainide test). The subjects were divided into two groups, the Brugada group and non-Brugada group. Further, the patients were divided into three subgroups on the base of symptoms (8, 7 symptomatic; 9, 13 syncope; 28, 12 asymptomatic group; in the Brugada and non-Brugada groups, respectively). Multivariate analyses evaluated the association between baseline clinical factors and the induction of VF.ResultsThe inducibility of VF was significantly (p<0.0001) higher in the Brugada group (n=33, 73%) than the non-Brugada group (n=4, 13%). The multivariate analysis demonstrated that symptoms (odds ratio (OR) 31.6; 95% confidence interval (CI): 2.3–430.6; p<0.01), type 1 electrocardiogram after pilsicainide test (OR 21.3; CI: 1.7–272.2; p<0.02), and syncope (OR 13.5; CI: 1.2–158.8; p<0.05) were strongly associated with the inducibility of VF, but not with family history, type 1 electrocardiogram in control, positive in late potential, maxΔST elevation (≧200μV) after pilsicainide test.ConclusionsThe symptoms, syncope, and type 1 electrocardiogram after pilsicainide test were independently associated with the electrophysiological substrate of VF in patients without apparent heart disease

Large-scale cohort study on the relationship between serum lipid concentrations and risk of cerebrovascular disease under low-dose simvastatin in Japanese patients with hypercholesterolemia: Sub-analysis of the Japan Lipid Intervention Trial (J-LIT)

金沢大学大学院医学系研究科　Background: The Japan Lipid Intervention Trial was a nationwide cohort study of 52,421 hypercholesterolemic patients treated with open-labeled simvastatin for 6 years under standard clinical practices. Cerebrovascular disease (CVD) is one of the leading causes of death in Japan, but the effect of hypercholesterolemia on CVD has not been well established in Japanese patients. This study aimed to determine the relationship between the risk of CVD and serum lipid concentrations during treatment in Japan. Methods and Results: Patients were treated with 5-10 mg/day of simvastatin and all, including those who discontinued simvastatin for any reason, had their lipid concentrations and incidence of CVD monitored for 6 years. Data of 41,088 patients were analyzed in this study, excluding those who had a history of coronary heart disease or CVD. The risk of cerebral infarction was higher in patients whose mean total cholesterol concentrations during treatment were ≥240 mg/dl, low-density lipoprotein cholesterol concentrations ≥160 mg/dl, triglycerides ≥150 mg/dl and high-density lipoprotein cholesterol concentrations <40 mg/dl. There was no obvious correlation between cerebral hemorrhage and serum lipid concentrations. Conclusion: Improvement of serum lipid concentrations is important for reducing the incidence of cerebral infarction