Shunichi Murano

Lipoprotein lipase mass and activity in post-heparin plasma from subjects with intra-abdominal visceral fat accumulation.

The purpose of this study was to investigate the possibility of impaired lipolysis of triglyceride‐rich lipoproteins in patients with abdominal visceral fat accumulation by assessing two major lipolytic enzymes in the plasma, lipoprotein lipase (LPL) and hepatic lipase (HL).

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.

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.

Characteristic Features of Long-Living Patients with Familial Hypercholesterolemia in Japan

Objective: To assess characteristics of long‐living familial hypercholesterolemics (FHs) in comparison with younger patients.

Comparison in decision-making between bulimia nervosa, anorexia nervosa, and healthy women: influence of mood status and pathological eating concerns

BackgroundDecision-making is reported to be impaired in anorexia nervosa (AN) and bulimia nervosa (BN), but the influence of mood status, pathophysiological eating, and weight concerns on the performance of decision-making ability between AN and BN is still unclear. The aims of this study were to investigate differential impairments in the decision-making process between AN, BN, and healthy controls (HC), and secondly, to explore the role of mood status, such as anxiety, depression, pathological eating, and weight concerns, in decision-making ability.MethodsPatients suffering from AN (nu2009=u200922), BN (nu2009=u200936) and age-matched HC (nu2009=u200951) were assessed for their decision-making abilities using the Iowa Gambling Task (IGT). Self-reported questionnaires including the Eating Disorder Examination Questionnaire (EDE-Q), the Bulimia Investigatory Test, Edinburgh (BITE), the Eating Disorders Inventory, the Maudsley Obsessive-Compulsive Inventory measuring obsessive-compulsive traits, the Hospital Anxiety and Depression Scale, and the Toronto Alexithymia Scale were used to assess pathological eating concerns and attitude to feelings.ResultsSignificant differences in IGT performance were observed between BN and HC. Significant negative correlation was found between IGT performance and the BITE symptom subscale in AN. In BN, there was a negative correlation between the EDE-Q weight concerns subscale and IGT performance. It was also found that increased anxiety, depression, and eating/weight concerns predicted poorer decision-making.ConclusionDifferent patterns of association between pathological eating concerns/behaviors and performances in decision-making ability were found between AN, BN, and HC. Anxiety, depressive mood status, and eating/weight concerns were related to decision-making ability.

Marked decrease in plasma apolipoprotein A-I and high density lipoprotein-cholesterol in a case with Werner syndrome.

The patient was a 39-year-old Japanese male with a body height of 160 cm and weight of 48 kg who was diagnosed as Werner syndrome of homozygote for mutation 4. His plasma total cholesterol (TC), triglycerides (TGs), high density lipoprotein-cholesterol (HDL-C) and apolipoprotein A-I (apo A-I) levels were 7.2, 2.1, 1 mmol/l and 128 mg/dl, respectively. During the clinical course of treatment of this patient, his plasma levels of HDL-C and apo A-I declined drastically to levels of as low as 0.2 mmol/l and 10 mg/dl, respectively, with concurrent reciprocal increase in plasma TG levels. Plasma HDL-C, apo A-I and TG levels gradually returned to original values. Lipoprotein lipase activity and mass in post-heparin plasma were markedly low when the apo A-I and HDL-C levels decreased to 10 mg/dl and 0.21 mmol/l, respectively, and these values improved when the apo A-I and HDL-C levels returned to more normal values of 106 mg/dl and 0.94 mmol/l, respectively. The result of direct sequence of the exon 3 and 4, and the promoter region of the apo A-I gene of the patient revealed no single nucleotide changes. These results suggest that in the present patient, impaired hydrolysis of TGs in TG-rich lipoproteins, is due at least in part to a decreased LPL enzyme level, reduced the formation of nascent HDL, resulting in unusually low plasma levels of HDL-C and apo A-I.

Lipid metabolism in arteriosclerotic arterial wall of rats

Arteriosclerotic lesions were formed in rat aorta by the administration of vitamin D2, a high-fat diet and a thyroid suppressing agent. This treatment increased the serum total cholesterol level to 12 times the control level. In the arteriosclerotic lesions that were induced the activities of lysosomal enzymes, such as acid phosphatase and acid lipase, were higher than in controls, that of acid cholesterol esterase was decreased, those of microsomal lipid-synthesizing enzymes--such as acyl-CoA synthetase and cholesterol ester synthesizing activity--were increased and that of neutral cholesterol esterase was decreased. These data suggest that lipid metabolism in arteriosclerotic lesions was changed, resulting in the accumulation of cholesterol esters in the aorta. Administration of high-fat diet and thyroid suppressing agent also increased the serum cholesterol levels to 12-fold the control level, but did not induce arteriosclerotic lesions. After this treatment the activities of hydrolyzing enzymes, such as acid and neutral cholesterol esterase and lipase, in the aorta increased, but the activities of lipid synthesizing enzymes also increased. These data suggest that lipid metabolism in the aorta in this condition changed to compensate for the large influx of serum lipids and to prevent arteriosclerosis. The roles of the serum lipid level, cell injury and lipid metabolism in the aorta in forming arteriosclerotic lesions are discussed on the basis of these results.

Potential for Pharmacological Intervention in Werner Syndrome

SummaryWerner syndrome is a rare genetic disease of premature aging which manifests itself in the form of a variety of aging-like phenomena and diseases. It is an appropriate target for aging research because it is clear that the complications must be caused by one original gene defect. Another reason why this disease is of particular interest is observed at the cellular level. The abbreviated lifespan of cultured fibroblasts from patients with this disorder parallels the clinical features of this accelerated aging disease.Recent studies have met with some success in identifying certain genes involved in Werner syndrome and the roles they might play in normal cellular senescence. Such advances might result in a therapeutic breakthrough for this essentially incurable genetic disease. In addition, such a treatment might find some application in the control of the normal aging process.

Type III hyperlipidaemia with primary hypothyroidism: a unique clinical course of hyperlipidaemia during replacement therapy of thyroid hormone

A patient is described with type III hyperlipidaemia and primary hypothyroidism who had a unique clinical course of hyperlipidaemia. The patient was a 65‐year‐old man with primary hypothyroidism. His plasma total cholesterol, triglyceride and high density lipoprotein‐cholesterol concentrations 1 year after starting thyroid hormone replacement therapy were 7.98, 4.04 and 0.72u2003mmol/l, respectively. His plasma apolipoprotein (apo) E level was 0.29u2003g/l and its phenotype was E2/2. Remarkably, this patient had no hyperlipidaemia before starting thyroid hormone replacement therapy but it became overt only after the hypothyroidism had been treated. Although we have not confirmed the mechanism for this, we speculate that a decrease in enzyme activities responsible for cholesterol production may have been sufficient to surpass the effect of apolipoprotein E2/2 and the decrease in enzyme activities involved in degrading and excreting plasma cholesterol, resulting in normolipidaemia.

Altered serum level of matrix metalloproteinase-9 and its association with decision-making in eating disorders.

The aims of this study were to determine whether the serum levels of precursor brain‐derived neurotrophic factor (proBDNF), mature BDNF (mBDNF), and matrix metalloproteinase‐9 (MMP‐9) are altered in patients with eating disorders (ED), including anorexia nervosa (AN) and bulimia nervosa (BN), and to explore whether those levels are associated with decision‐making abilities.