Pnina Green

Lovastatin Therapy in Hypercholesterolemia: Effect on Fibrinogen, Hemorrheologic Parameters, Platelet Activity, and Red Blood Cell Morphology

The effect of lovastatin therapy on blood rheology was investigated in 26 hypercholesterolemia patients. Treatment with lovastatin was associated with a significant improvement in whole blood filtration time and a tendency toward normalization in red blood cell morphology. A significant increase was observed in fibrinogen level, in ADP‐induced platelet aggregation, in the percentage of “big” platelets, and in platelet count. The viscosity of whole blood and plasma and the percentage of aggregated platelets did not change significantly. The cause for these hemorrheologic changes and their role in influencing the coronary risk of lovastatin‐treated hypercholesterolemia patients should be further investigated.

Pathways of polyunsaturated fatty acid utilization: implications for brain function in neuropsychiatric health and disease.

Essential polyunsaturated fatty acids (PUFAs) have profound effects on brain development and function. Abnormalities of PUFA status have been implicated in neuropsychiatric diseases such as major depression, bipolar disorder, schizophrenia, Alzheimers disease, and attention deficit hyperactivity disorder. Pathophysiologic mechanisms could involve not only suboptimal PUFA intake, but also metabolic and genetic abnormalities, defective hepatic metabolism, and problems with diffusion and transport. This article provides an overview of physiologic factors regulating PUFA utilization, highlighting their relevance to neuropsychiatric disease.

Lovastatin therapy in heterozygous familial hypercholesterolaemic patients: effect on blood rheology and fibrinogen levels

Abstract. Thirteen heterozygous familial hypercholesterolaemic patients were treated with lovastatin for 1 year, and were investigated for the effect on lipid profile, blood rheology and fibrinogen levels. A significant dose‐dependent reduction in serum levels of total and LDL‐cholesterol, Apo B and the ratio of total cholesterol to HDL‐cholesterol was noted. Improvement in red blood cell filterability and an increase in fibrinogen levels were also observed. We conclude that the hypocholesterolaemic effect of lovastatin in familial hypercholesterolaemia is accompanied by changes in blood rheology. While some of these haemorheological changes may be considered beneficial, others may be regarded as unfavourable. The net effect of lovastatin therapy on the coronary risk of familial hypercholesterolaemic patients warrants further investigation.

Arachidonic acid-containing phosphatidylcholine species are increased in selected brain regions of a depressive animal model: Implications for pathophysiology

The Flinders Sensitive Line (FSL) rat is a genetic animal model of depression. Following recent findings that the brain fatty acid composition of FSL is characterised by increased arachidonic acid (AA), we used electrospray tandem mass spectrometry and (1)H-NMR to examine lipid species in different brain areas. Cholesterol and sphingolipids were increased in the hypothalamus of the FSL rats. Furthermore, arachidonic acid-containing phosphatidylcholine (AA-PC) species were elevated with PC16:0/20:4, PC18:1/20:4 and PC18:0/20:4 (p<0.003) increased in the hypothalamus and striatum. In contrast, there was a decrease in some docosahexaenoic acid (DHA)-containing species, specifically PC18:1/22:6 (p<0.003) in the striatum and PE18:1/22:6 (p<0.004) in the prefrontal cortex. Since no significant differences were observed in the erythrocyte fatty acid concentrations, dietary or environmental causes for these observations are unlikely. The increase in AA-PC species which in this animal model may be associated with altered neuropathy target esterase activity, an enzyme involved in membrane PC homeostasis, may contribute to the depressive phenotype of the FSL rats.

Pregnancy in a homozygous familial hypercholesterolemic patient treated with long-term plasma exchange

We describe the first pregnancy in a homozygous familial hypercholesterolemic woman who started plasma exchange therapy 3 years before she became pregnant. We especially studied the effects of plasma exchange on lipid profile, uteroplacental circulation, and pregnancy course.

BBS4 directly affects proliferation and differentiation of adipocytes

BBS4 is one of several proteins whose defects cause Bardet–Biedl syndrome (BBS), a multi-systemic disorder, manifesting with marked obesity. BBS4 polymorphisms have been associated with common non-syndromic morbid obesity. BBS4 obesity molecular mechanisms, and the role of the BBS4 gene in adipocyte differentiation and function are not entirely known. We now show that Bbs4 plays a direct and essential role in proliferation and adipogenesis: silencing of Bbs4 in 3T3F442A preadipocytes induced accelerated cell division and aberrant differentiation, evident through morphologic studies (light, scanning and transmission electron microscopy), metabolic analyses (fat accumulation, fatty acid profile and lipolysis) and adipogenic markers transcripts (Cebpα, Pparγ, aP2, ADRP, Perilipin). Throughout adipogenesis and when challenged with fat load, Bbs4 silenced cells accumulate significantly more triglycerides than control adipocytes, albeit in smaller (yet greater in number) droplets containing modified fatty acid profiles. Thus, greater fat accumulation in the silenced cells is a consequence of both a higher rate of adipocyte proliferation and of aberrant differentiation leading to augmented aberrant accumulation of fat per cell. Our findings suggest that the BBS obesity might be partly due to a direct role of BBS4 in physiological and pathophysiological mechanisms that underlie adipose tissue formation relevant to obesity.

Big platelets in hyperlipidemic patients.

Both “big” platelets and hyperlipidemia are associated with increased coronary risk. This study was undertaken to search for a possible effect of various hypolipidemic drugs on big platelets. The percentage of big platelets, assessed microscopically, was measured in 66 patients who had hyperlipidemia of various types. Twenty‐seven patients with hypertriglyceridemia were randomly selected to receive either fish oil or placebo in a crossover study. Another group of 39 patients with hypercholesterolemia, among them 13 with heterozygous familial hypercholesterolemia (FH), received lovastatin. The pretreatment level of big platelets was elevated, and similar in all groups: 23.3 ± 12% versus 22 ± 9%, in the fish oil versus placebo group, 19.1 ± 6.3% versus 24 ± 11% in the FH versus non‐FH primary hypercholesterolemia group (reference value, 6.8 ± 3.5%). After treatment, despite the improvement in lipoprotein profile, the percentage of big platelets did not change. The relationship between lipid reduction and big platelets is thus questionable, and necessitates further study.