Antiobesity activity of a sphingosine 1-phosphate analogue FTY720 observed in adipocytes and obese mouse model

Higher levels of body fat are associated with an increased risk for development numerous adverse health conditions. FTY720 is an immune modulator and a synthetic analogue of sphingosine 1-phosphate (S1P), activated S1P receptors and is effective in experimental models of transplantation and autoimmunity. Whereas immune modulation by FTY720 has been extensively studied, other actions of FTY720 are not well understood. Here we describe a novel role of FTY720 in the prevention of obesity, involving the regulation of adipogenesis and lipolysis in vivo and in vitro. Male C57B/6J mice were fed a standard diet or a high fat diet (HFD) without or with FTY720 (0.04 mg/kg, twice a week) for 6 weeks. The HFD induced an accumulation of large adipocytes, down-regulation of phosphorylated AMP-activated protein kinase alpha (p-AMPKalpha) and Akt (p-Akt); down-regulation of hormone-sensitive lipase (HSL), adipose triglyceride lipase (ATGL) and perilipin mRNA as well as up-regulation of phosphorylated HSL (p-HSL, Ser563) and glycogen synthase kinase 3 alpha/beta (p-GSK3alpha/beta). All these effects were blunted by FTY720 treatment, which inhibited adipogenesis and promoted lipolysis. Also, FTY720 significantly decreased lipid accumulation in maturing preadipocytes. FTY720 down-regulated the transcriptional levels of the PPARgamma, C/EBPalpha and adiponectin, which are markers of adipogenic differentiation. FTY720 significantly increased the release of glycerol and the expression of the HSL, ATGL and perilipin, which are regulators of lipolysis. These results show that FTY720 prevented obesity by modulating adipogenesis and lipolysis, and suggest that FTY720 is used for the treatment of obesity.

Statistics series (III): t test and Wilcoxon test

No abstract available.

A Case of Femoral Artery Pseudoaneurysm , which was Developed after Interventional Cardiology Procedure , Treated with Color Doppler Ultrasound-Guided Direct Compression

Vascular complications such as hematoma, pseudoaneurysm and arteriovenous fistula that occur after intracoronary or intracardiac procedures are responsible for considerable morbidity and some mortality. Iatrogenic aneurysms are usually postcatheterization pseudoaneurysms of the femoral artery. Nowadays, it is not uncommon as a consequence of more complex interventional procedures, larger catheters and prolonged anticoagulation treatment. Surgical repair has been mainstay of treatment for pseudoaneurysm. However, recently has it been shown that color Doppler ultrasound-guided direct, noninvasive compression of the pseudoaneurysm stops the blood flow in the communication and lead to pseudoaneurysm clotting and obliteration. We report a case of pseudoaneurysm in femoral artery, which was developed at the right inguinal puncture site in 74 year old male patient with myocardial infarction who had received continuous intravenous infusion of heparin and had undergone primary percutaneous coronary angioplasty and temporary pacemaker insertion treated successfully with color Doppler ultrasound guided direct compression.

A Case of Double-Chamber Right Ventricle Associated with Ventricular Septal Defect

Double-chamber right ventricle (DCRV) is a rare congenital heart disease consisting in right ventricular obstruction due to one or several anomalous muscle bundles that divide the right ventricle into two chambers. The right ventricular outflow tract obstruction is generally progressive in these patients. A ventricular septal defect is one of the commonly associated malformations. A 23-year-old woman with exertional dyspnea was admitted to our hospital and undertaken echocardiography, cardiac catheterization and both ventricular angiograms. The diagnosis was established and report with review of literatures.

Relation of Carotid Artery Intima-Media Thickness and Atherosclerotic Plaque with the Extent of Coronary Artery Stenosis

BACKGROUND: Noninvasive measurements that relate to the extent and severity of coronary atherosclerosis have long been sought for clinical screening of patients with chest pain syndromes and for use in clinical trials. Intima-media thickeness (IMT) of the carotid artery has been suggested to be associated with coronary artery atherosclerosis. In this study, we tried to assess the relation of carotid artery atherosclerosis by B-mode ultrasonography with presence and severity of coronary artery disease. METHOD: We studied 57 patients (36 men, 21 women) with ischemic heart disease, mean age 65+/-8 yrs (48 to 83 yrs), who underwent both coronary angiography and carotid ultrasonography with 10 MHz transducer. The patients who had received revascularization procedure were excluded. We classified the patients into two groups, the control group without significant coronary stenosis (18 patients) and the coronary artery disease (CAD) group (39 patients) with significant luminal stenosis (> or =50%). The CAD group was divided into single vessel disease group (SVD, 19 patients) and multivessel disease group (MVD, 20 patients). IMT was measured in far wall of common carotid artery (CCA) at 10 mm proximal to carotid bulb and abnormal IMT was defined if the measurement was greater than mean IMT+2SD of control group. Serum total cholesterol (TC), low density lipoprotein (LDL), high density lipoprotein (HDL), triglyceride (TG), Lipoproteinp (a)(Lp(a)) were measured and history of hypertension, diabetes mellitus, and smoking were investigated. RESULTS: A significant difference in IMT of the CCA was found between control and CAD group (0.76+/-0.09 mm vs. 0.97+/-0.20 mm; p<0.0001). Also a significant difference in the number of atherosclerotic plaque was found between the two groups (control; 0.67+/-1.14 vs. CAD; 1.87+/-1.75; p<0.005). In the CAD group, both mean IMT and numbers of athero-sclerotic plaque tended to increase in MVD group compared with SVD group (1.03 mm vs. 0.91 mm; p=NS, 2.65 vs. 1.05; p<0.05). The sensitivity of IMT for prediction of significant CAD was 66.7%, the specificity 83.3%, the positive predictive value 89.7%, and the negative predictive value 53.6%. The sensitivity of plaque presence on the carotid artery for prediction of CAD was 71.8%, the specificity 61.3%, the positive predictive value 80.3% and the negative predictive value 50.5%. Among risk factor, diabetes mellitus and Lp (a) were correlated well with IMT of CCA, Hypertension was correlated with atherosclerotic plaque. History of smoking was correlated with coronary artery disease. CONCLUSION: Increases in IMT and plaque of the carotid artery, as measured noninvasively by ultrasonography, can be used as a predictor of significant coronary artery stenosis.

A Case of Systemic Amyloidosis

Systemic amyloidosis is an uncommon disease characterized by deposits of fibrillar aggregates of monoclonal immunoglobuloin light chains in vital organs. This amyloid deposit cause cardiac or renal dysfunction and ultimately, death. Cardiac amyloidosis may be asymptomatic or important causes of progressive heart failure and refractory arrhythmia. Cardiac involvement from AL amyloidosis is rapidly fatal. The amyloidoses are classified according to the biochemical nature of the fibril-forming protein. Cardiac amyloidosis is common in primary (AL) and heterofamilial amyloidosis and very rare in the secondary (AA) form. As we experienced a case of systemic amyloidosis affected heart, liver and kidney, which was confirmed by histology. We present a 57-year-old female case with literature review.