Masaki Shinomiya

Abdominal wall fat index, estimated by ultrasonography, for assessment of the ratio of visceral fat to subcutaneous fat in the abdomen

PURPOSE To establish a new index of regional fat distribution using ultrasonography for assessment of the ratio of the visceral fat area (V) to the subcutaneous fat area (S) (V/S ratio). SUBJECTS AND METHODS The subjects examined were 62 patients (23 males and 39 females); 51 patients had hyperlipidemia and 11 patients had glucose intolerance. The mean body mass indices ranged from 20.3 to 42.9. The mean age of the patients was 44 +/- 13 years. The thicknesses of the preperitoneal fat layer (P) and subcutaneous fat layer (S) in the abdomen were measured by ultrasonography and the P/S ratio was calculated. The V/S ratio was obtained with radiographic computed tomography. RESULTS Of the various P/S ratios examined, the ratio of the maximum thickness of preperitoneal fat to the minimum thickness of subcutaneous fat was most closely correlated with the V/S ratio (r = 0.746, p < 0.0001). This ratio was termed the abdominal wall fat index (AFI). AFI was positively correlated with serum triglyceride levels and negatively correlated with high-density lipoprotein cholesterol (r = -0.312, p < 0.05), whereas the V/S ratio was correlated with triglyceride levels. AFI was positively correlated with basal insulin levels in both men and women. CONCLUSION These results suggest that AFI measured by ultrasonography may be a new indicator of visceral fat deposition, and may reflect metabolic disorders such as lipid metabolism and glucose metabolism disorders.

Multicenter collaborative randomized parallel group comparative study of pitavastatin and atorvastatin in Japanese hypercholesterolemic patients Collaborative study on hypercholesterolemia drug intervention and their benefits for atherosclerosis prevention (CHIBA study)

AIMS To compare the efficacy and safety of pitavastatin and atorvastatin in Japanese patients with hypercholesterolemia. METHODS AND RESULTS Japanese patients with total cholesterol (TC) > or = 220 mg/dL were randomized to receive pitavastatin 2 mg (n=126) or atorvastatin 10 mg (n=125) for 12 weeks. The primary endpoint was percent change from baseline in non-HDL-C level after 12 weeks of treatment. Reduction of non-HDL-C by pitavastatin treatment (39.0%, P=0.456 vs. atorvastatin) was non-inferior to that by atorvastatin (40.3%). Both pitavastatin and atorvastatin also significantly reduced LDL-C by 42.6% and 44.1%, TC by 29.7% and 31.1%, and TG by 17.3% and 10.7%, respectively, at 12 weeks without intergroup differences. HDL-C showed a significant increase at 12 weeks with pitavastatin treatment (3.2%, P=0.033 vs. baseline) but not with atorvastatin treatment (1.7%, P=0.221 vs. baseline). Waist circumference, body weight and BMI were significantly correlated with percent reduction of non-HDL-C in the atorvastatin group, whereas pitavastatin showed consistent reduction of non-HDL-C regardless of the body size. In patients with metabolic syndrome, LDL-C was reduced significantly more in patients receiving pitavastatin when compared with those receiving atorvastatin. AST, ALT and gammaGTP increased significantly in patients receiving atorvastatin but not in those receiving pitavastatin. Both treatments were well tolerated. CONCLUSION Pitavastatin 2 mg and atorvastatin 10 mg are equally effective in improving the lipid profile and were well tolerated in Japanese patients with hypercholesterolemia.

Enhanced arterial intimal thickening after balloon catheter injury in diabetic animals accompanied by PDGF β-receptor overexpression of aortic media

Abstract. Cultured aortic smooth muscle cells (SMC) of diabetic rats and rabbits, which overexpress platelet‐derived growth factor (PDGF) β‐receptor compared with controls, have a unique phenotype. In this study we report on the PDGF β‐receptor overexpression in aortas of diabetic animals and the increased intimal thickening of carotid arteries in diabetic rabbits after balloon catheter injury compared with that in controls. In diabetic aortas with no treatments of balloon catheter injury, intimal thickening was not observed in spite of the overexpression of PDGF β‐receptor, indicating that the growth property of medial SMC in diabetic aortas was changed before the intimal thickening could take place. PDGF is known to be the main contributor to the intimal thickening induced by balloon catheter injury, which is one of several forms of arterial injuries. Intimal thickening after balloon catheter injury in diabetic rabbits increased compared with that in controls. These results imply that PDGF β‐receptor overexpression of SMC in medial layers plays an important role in intimal thickening in the formation of advanced diabetic macroangiopathy.

Studies on cholesterol esterase in rat arterial wall

Cholesterol esterase activity was estimated in homogenates of rat arterial wall using radioactive cholesteryl oleate incorporated into phospholipid vesicles as a substrate. The labeled oleic acid was separated from the ester by addition of benzene-chloroform-methanol mixture. Under these conditions, two pH optima were found at about 4.5 and 7.5. Most of the activities at pH 4.5 and 7.5 were found in the lysosomal and microsomal fraction, respectively. No enzyme activity was detected when the substrate vesicles were prepared with phosphatidylethanolamine or sphingomyelin, but the activity was higher when the substrate vesicles were prepared with phosphatidylserine and highest when they were prepared with phosphatidylcholine. The relationship between enzyme regulation and lipid deposition in the arterial wall is discussed.

Dose-dependent hypolipidemic effect of an inhibitor of HMG-CoA reductase, pravastatin (CS-514)) in hypercholesterolemic subjects A double blind test

The hypolipidemic effect of a new HMG-CoA reductase inhibitor, pravastatin, was examined. The reductions of serum cholesterol and LDL-cholesterol were dose-dependent and significant differences were observed between placebo and 10 or 20 mg groups (P less than 0.01), and 10 and 20 mg (P less than 0.05) groups. The reduction rate of cholesterol after 8 weeks during medication was 16.1% in the 10 mg group, 20.5% in the 20 mg group compared to baseline serum cholesterol levels. LDL-cholesterol decreased by 23.9% in the 10 mg group, and 29.8% compared to baseline LDL-cholesterol in the 20 mg group. The lowering of total cholesterol was entirely attributed to a reduction in LDL-cholesterol.

Inhibition of intimal thickening of the carotid artery of rabbits and of outgrowth of explants of aorta by probucol

The effect of administration of probucol in preventing intimal thickening of rabbit carotid artery after balloon catheter injury and the mechanism of action of the drug were studied. Groups of 6 male New Zealand-White rabbits were given normal diet (Group I), high cholesterol diet (Group II) or high cholesterol diet plus probucol (Group III) for 4 weeks. Balloon catheter injury was made in week 2 and animals were killed in week 4. No significant differences in the total cholesterol levels in Groups II and III were found in week 4. The medians of areas of the intimal layer in cross-sections of the carotid arteries of Groups I, II and III were 0.237, 0.475 and 0.309 mm2, respectively. Thus high-cholesterol diet increased the thickness of the intimal layer and probucol reduced its effect. There were no significant differences in the areas of the medial layers in these 3 groups. For the examination of the mechanism of the effect of probucol, rabbits were given chow containing 0.5% cholesterol with and without 0.5% probucol (7 rabbits each) and then the numbers of explants from their aortas showing outgrowth were compared. The plasma total cholesterol levels of these two groups were the same. The probucol concentrations in the plasma and aorta of the former group were 18.6 +/- 13.2 micrograms/ml and 7.3 +/- 5.4 micrograms/g wet tissue, respectively. The number of explants showing outgrowth on day 14 was suppressed by 34% in the probucol-treated group.(ABSTRACT TRUNCATED AT 250 WORDS)

Incidence of childhood obesity over the last 10 years in Japan

1. Childhood obesity has been increasing for the last ten years in Tateyama City. Obesity in boys between the ages of 11 to 13 years was especially prominent. 2. Childhood obesity hardly improved especially in middle and morbid obesity. Eighty-five percent of light obesity in children lead to adult obesity. 3. Complications such as hypertension, serum lipid disorder and fatty liver were also observed in childhood obesity. Considering that Tateyama City is a typical Japanese country city, the above results could be representative of Japanese childhood obesity. Recent increases in childhood obesity might be due to the westernized dietary habit.

Single LDL apheresis improves serum remnant-like particle-cholesterol, C-reactive protein, and malondialdehyde-modified-low-density lipoprotein concentrations in Japanese hypercholesterolemic subjects.

BACKGROUND Single low-density lipoprotein (LDL)-apheresis may affect serum remnant-like particle-cholesterol (RLP-C), C-reactive protein (CRP) and malondialdehyde-modified (MDA)-LDL concentrations. SUBJECTS AND METHODS Six subjects with hypercholesterolemia (five men, one woman) were involved in this study. Mean age and body mass index of the study subjects were 58+/-3.1 years and 23.6+/-2.07 kg/m(2), respectively. Five of the subjects were diagnosed as heterozygous familial hypercholesterolemia (FH) because of having both marked hypercholesterolemia and Achilles tendon xanthomas. LDL apheresis was introduced and continued using a dextran sulfate cellulose adsorption column technique every 2 weeks. Serum RLP-C was measured using an immunoaffinity mixed gel containing anti-apolipoprotein A-I and anti-apolipoprotein B monoclonal antibody. Serum CRP was measured by latex-enhanced assay. Serum MDA-LDL was measured using monoclonal antibody against MDA-LDL (ML25). RESULTS Combined treatment in the steady state pre-treatment yielded a total, LDL- and HDL-cholesterol, and TG concentrations of 5.39+/-0.81, 3.82+/-1.03, 1.24+/-0.29 and 0.92+/-0.43 mmol/l, respectively, and a post-treatment total, LDL- and HDL-cholesterol and TG concentrations of 2.79+/-0.37 (-48%, p<0.001), 1.63+/-0.29 (-57%, p<0.001), 1.18+/-0.26 (-5%, NS) and 0.23+/-0.11 mmol/l (-75%, p<0.001), respectively. Serum RLP-C and CRP concentrations showed a substantial reduction [-73%, p<0.05 for RLP-C; -56%, p<0.05 for CRP] during this procedure. In addition, LDL apheresis was found to also cause a marked reduction in serum MDA-LDL concentration (-61%, p<0.05). CONCLUSION LDL-apheresis is an effective treatment for removing atherogenic factors RLP-C, CRP and MDA-LDL from sera.

Effect of pantethine on cholesterol ester metabolism in rat arterial wall.

The total serum cholesterol level in rats fed on a high cholesterol diet (HCD) for 16 weeks was markedly higher than that in rats fed on a normal diet (ND), but pantethine reduced the increased level in rats fed on HCD (P less than 0.05). Acid cholesterol esterase activity (acid CEase) of arterial wall homogenates from rats fed on HCD was significantly lower than that of rats fed on ND (P less than 0.005). Acid CEase activity in the arterial wall of rats fed on HCD for 8 weeks and then ND for 8 weeks was less than that of rats fed on ND for 16 weeks. Acid CEase activity in the arterial wall was increased in rats fed on pantethine-containing diet. The ratio of cholesterol ester synthesizing activity to neutral cholesterol esterase (neutral CEase) activity was higher in rats fed on NCD than in those fed on ND. The ratio was lower in rats on the pantethine-containing diet than in those on NCD. The relationship between hypercholesterolemia and lipid metabolism in the arterial wall and effects of pantethine are discussed on the basis of these results.

Carvastatin suppresses intimal thickening of rabbit carotid artery after balloon catheter injury probably through the inhibition of vascular smooth muscle cell proliferation and migration

In order to test whether a 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor has an anti-atherogenic activity, the effects of carvastatin, a newly developed potent inhibitor, and pravastatin were examined on the intimal thickening of the artery after the endothelial denudation induced by balloon catheter injury. Rabbits were divided into four groups; control, pravastatin-treated (20 mg kg(-1) day(-1)) and two of carvastatin-treated groups (10 or 20 mg kg(-1) day(-1)). Two weeks after balloon catheter injury, the areas of intima and media of the injured carotid arteries were determined, and the ratios of intima to media (I/M) were calculated as an index of intimal thickening. Average I/M ratios of the injured artery were 0.42+/-0.05 for control, 0.49+/-0.07 for pravastatin, 0.19+/-0.03 (10 mg kg(-1) day(-1)) and 0.20+/-0.04 (20 mg kg(-1) day(-1)) for carvastatin-treated rabbits, respectively. Thus, carvastatin reduced I/M ratio of the injured artery to approximately half versus control, but pravastatin failed to suppress the intimal thickening. For in vitro study, vascular smooth muscle cells (SMC) from rabbit aorta were explanted, then cultured, and the effects of carvastatin on SMC migration and SMC proliferation were also examined. Carvastatin inhibited dose-dependently SMC migration and SMC proliferation with IC50 values of 0.5 microM and 1 microM, respectively. These inhibitory effects of carvastatin were cancelled by the coexistence of mevalonate, a metabolite of cholesterol synthesis. Our results suggest that carvastatin may be useful in rabbits as an anti-atherogenic drug by means of the inhibition of SMC migaration or SMC proliferation.