Kohji Shirai

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.

Effect of glycyrrhizin on lysis of hepatocyte membranes induced by anti‐liver cell membrane antibody

Studies were made on why glycyrrhizin injection decreases the plasma aspartate aminotransferase (AST) and alanine aminotransferase activities in patients with chronic hepatitis.1 For this, rat hepatocytes were isolated, and incubated with antibody raised against rat liver cell membranes, and the effect of glycyrrhizin on their release of transaminase was investigated. Isolated rat hepatocytes released AST on incubation with anti‐liver cell antibody in the presence of complement. At this time, their endogenous phospholipase A2 activity was increased. Cultured hepatocytes also released the transaminase in the presence of venom phospholipase A2. Glycyrrhizin suppressed the release of transaminase in the presence of either anti‐liver cell membrane antibody or phospholipase A2. These results suggest that antibody treatment raised the phospholipase A2 activity in liver cell membranes, resulting in release of transaminases, and that glycyrrhizin suppressed this increase in phospholipase A2 activity and so inhibited the release of transaminase.

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.

Type I hyperlipoproteinemia caused by lipoprotein lipase defect in lipid-interface recognition was relieved by administration of medium-chain triglyceride

We have previously reported lipoprotein lipase with a defect of lipid-interface recognition in a patient with type I hyperlipoproteinemia. In this patient, lipoprotein lipase from post-heparin plasma (PHP) hydrolyzed monomeric substrate tributyrin, but scarcely hydrolyzed triolein emulsified with Triton X-100 and that in very-low-density lipoproteins ([VLDL] d < 1.006 g/mL), and did not bind to VLDL. The triglyceride (TG) level of this patient did not decrease to less than 1,000 mg/dL with a low-fat diet (1,400 kcal containing 10 g fat/d). When the patient took 30 g medium-chain TG (MCT) in addition to the 1,400-kcal diet, her serum TG level decreased to 250 mg/dL and her clinical signs improved. The low clearance rate of serum TG with heparin injection improved after intake of MCT. Caproic acid levels were maintained at 1.4% and 2.6% in chylomicrons and VLDL after MCT intake, respectively. The patients lipoprotein lipase hydrolyzed triolein emulsified with 2% tricaprin at the same rate as that of control lipoprotein lipase. The patients lipoprotein lipase-catalyzed hydrolyzing rate of triolein in chylomicrons obtained after MCT administration was also enhanced up to 70% of that of control lipoprotein lipase. These findings suggest that hypertriglyceridemia caused by lipoprotein lipase with a defect in lipid-interface recognition could be relieved with the administration of medium-chain TG, and that one of the mechanisms of this effect might be a modification of TG-rich lipoproteins by MCT.

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.

Proliferation and LDL binding of cultured intimal smooth muscle cells from rabbits

Cultured intimal smooth muscle cells (SMC) were prepared from rabbits in which a cannula had been inserted into the abdominal aorta 4 weeks previously. The patterns of growth proliferative rates, and lipoprotein metabolism of cultures of intimal and medial SMC from intact aortic media were compared. Intimal SMC proliferated more rapidly than medial SMC. Both low density lipoprotein (LDL) and acetylated LDL bound to intimal SMC, whereas only LDL bound to medial SMC. These findings suggest a phenotypic difference between intimal and medial SMC.

Effect of nifedipine administration on pulse wave velocity (PWV) of chronic hemodialysis patients—2-year trial

SummaryPulse wave velocity (PWV) is known to reflect the stiffness of the aorta [2,7], one of the major features of atherosclerosis. To clarify the severity and progression mechanism of atherosclerosis in hemodialysis patients and the preventive effect of nifedipine, PWV was annually measured for 2 years, and the change of PWV and contributory factors were analyzed. PWV in hemodialysis patients was faster than in age-matched normal controls. PWV was correlated with the duration of hemodialysis. ΔPWV, which is obtained from the difference in PWV over 1 year, was positively correlated with age, high blood pressure, and serum cholesterol levels and was negatively correlated with HDL levels. The Ca×Pi value was also positively correlated with ΔPWV. Nifedipine was administered to 47 patients for 2 years, and the change of PWV was compared with age-matched control hemodialysis patients. The PWV of the control group was gradually increased by 10%. The PWV of the group given nifedipine decreased by 2%. These results suggested that administration of nifedipine may prevent the progression of PWV in hemodialysis patients and may decrease the progression of atherosclerosis.

Studies on Lipase in Rat Brain

Lipase activity was measured in homogenates of rat cerebral hemispheres using radioactive glycerol trioleate emulsified with Triton X‐100 as substrate. The labeled oleic acid was separated from the ester with a methanol‐chloroform‐heptane mixture. Under these assay conditions, the activity showed pH optima at about 5.5 and 7.5. The final products of these lipase activities were suggested to be free fatty acid and glycerol.