Fine ice particles formed at dew point of -70℃

第2回極域科学シンポジウム/第34回気水圏シンポジウム 11月14日（月） 統計数理研究所 セミナー室

Comment on: Nathan DM, Buse JB, Davidson MB et al. (2006) Management of hyperglycaemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy. A consensus statement from the American Diabetes Association and the European Association for the Study of Diabetes.

金沢大学大学院医学系研究科環境社会医

Tumor necrosis factor-α-induced production of plasminogen activator inhibitor 1 and its regulation by pioglitazone and cerivastatin in a nonmalignant human hepatocyte cell line

金沢大学大学院医学系研究科環境社会医学Plasminogen activator inhibitor 1 (PAI-1) is an important mediator of atherosclerosis and liver fibrosis in insulin resistance. Circulating levels of PAI-1 are elevated in obese individuals, and PAI-1 messenger RNA is significantly higher in the livers of obese type 2 diabetic individuals than in nonobese type 2 diabetic individuals. To address the mechanism underlying the up-regulation of hepatic PAI-1 in obesity, we tested the effects of tumor necrosis factor α (TNF-α), an important link between obesity and insulin resistance, on PAI-1 production in the nonmalignant human hepatocyte cell line, THLE-5b. Incubation of THLE-5b cells with TNF-α stimulated PAI-1 production via protein kinase C-, mitogen-activated protein kinase-, protein tyrosine kinase-, and nuclear factor-κB-dependent pathways. A thiazolidinedione, pioglitazone, reduced TNF-α-induced PAI-1 production by 32%, via protein kinase C- and nuclear factor-κB-dependent pathways. The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor cerivastatin inhibited TNF-α-induced PAI-1 production by 59%, which was reversed by coincubation with mevalonic acid. In conclusion, obesity and TNF-α up-regulation of PAI-1 expression in human hepatocytes may contribute to the impairment of the fibrinolytic system, leading to the development of atherosclerosis and liver fibrosis in insulin-resistant individuals. A thiazolidinedione and a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor may thus be candidate drugs to inhibit obesity-associated hepatic PAI-1 production. © 200

Renoprotective effects of atorvastatin compared with pravastatin on progression of early diabetic nephropathy

Introduction: Several studies have shown that statins suppress the progression of diabetic nephropathy. However, few reports have directly compared the renoprotective effects between potent and conventional statins. Materials and Methods: Patients with diabetic nephropathy, selected as those with a serum creatinine level of 0.9-1.5 mg/dL and simultaneously having either microalbuminuria or positive proteinuria, were randomly assigned to one of three groups: a conventional diet therapy group, a group given 10 mg of pravastatin and a group given 10 mg of atorvastatin. Renal function was evaluated before and after a 12-month period of therapy. Results: The atorvastatin group had a significant decrease in low-density lipoprotein cholesterol at 3 months and thereafter compared with the other groups. The urinary albumin-to-creatinine ratio significantly decreased in the atorvastatin group; the degree of this decrease was significantly greater than that in the diet therapy group. The kidney function estimated with cystatin C (CysC) and the estimated glomerular filtration rate calculated from CysC were significantly preserved in the atorvastatin group compared with the pravastatin group. In a multivariate regression analysis, the use of atorvastatin was the only explanatory variable for the changes in CysC; this was independent of changes in low-density lipoprotein cholesterol. Conclusions: Atorvastatin is more effective than pravastatin for the prevention of increase in CysC, and this renoprotective effect was considered to a result of the pleiotropic effect of atorvastatin independent of its lipid-lowering effect. This study was registered with UMIN (no. UMIN 000001774). © 2014 The Authors

Pharmacokinetics and pharmacodynamics of insulin aspart in patients with Type 2 diabetes: Assessment using a meal tolerance test under clinical conditions

Few studies have evaluated the pharmacokinetics of rapid-acting insulin analogues in patients with Type 2 diabetes, especially under clinical conditions. The aim of the present study was to assess both the pharmacokinetics and pharmacodynamics of insulin aspart in Type 2 diabetic patients who were being treated with the analogue alone. Meal tolerance tests with and without self-injection of a customary dose of insulin aspart (0.05-0.22 U/kg) were conducted in 20 patients in a randomized cross-over study. The dose of insulin aspart (per bodyweight) was significantly correlated with both the maximum concentration (r 2 = 0.59; P < 0.01) and area under the concentration-time curve for insulin aspart (r 2 = 0.53; P < 0.01). However, the time to maximum concentration (T max), which varied widely from < 60 to ≥ 120 min, was not associated with either dosage (r 2 = 0.02; P = 0.51) or body mass index (r 2 = 0.02; P = 0.57). Injection of insulin aspart exacerbated delayed hyperinsulinaemia after meal loading, mainly in patients with T max ≥ 120 min. With regard to pharmacodynamics, insulin aspart had favourable effects on postprandial hyperglycaemia, hyperglucagonaemia and hyperlipidaemia. The T max for this insulin analogue differed greatly between individuals and delayed hyperinsulinaemia was particularly exacerbated in patients with higher T max values. Identification of the factors contributing to interindividual variation in the absorption lag time is essential for improving the efficacy and safety of insulin aspart. © 2012 The Authors. Clinical and Experimental Pharmacology and Physiology © 2012 Blackwell Publishing Asia Pty Ltd

Selective estrogen receptor modulator raloxifene-associated aggravation of nonalcoholic steatohepatitis.

金沢大学大学院医学系研究科環境社会医学A 53-year-old postmenopausal woman, who had a family history of cryptogenic liver cirrhosis, was diagnosed with osteoporosis, and started on the selective estrogen receptor modulator (SERM) raloxifene 60 mg/day orally. She developed marked liver dysfunction. Her body mass index (BNU) was 26.5. Her blood chemistry indicated AST 342 IU/L, ALT 356 IU/L, and hyaluronic acid 255 ng/mL. An oral glucose tolerance test showed impaired glucose tolerance with marked insulin resistance. Histologically, we diagnosed this case as having pre-cirrhotic nonalcoholic steatohepatitis (NASH). This is the first histologically confirmed case of NASH that was aggravated by raloxifene. © 2007 The Japanese Society of Internal Medicine