n-3 fatty acids do not enhance LDL susceptibility to oxidation in hypertriacylglycerolemic hemodialyzed subjects.

Recent data suggest that treatment with n-3 fatty acids could enhance the susceptibility of plasma low-density-lipoprotein (LDL) to oxidation. Twelve hypertriacylglycerolemic, hemodialyzed patients were treated with 2.5 g n-3 fatty acids/d for 2 mo. Treatment was then withdrawn for 2 mo (washout phase). Plasma total cholesterol and LDL cholesterol increased significantly (9% and 28%) and plasma triacylglycerols decreased significantly after the n-3 phase compared with baseline and washout values. LDL susceptibility to oxidation was tested by oxidation of LDL particles with 2,2'-azobis (2-amidinopropane) dihydrochloride (AAPH). No significant changes were observed for the lag phase and the peroxidation rate. The vitamin E content of LDL also did not change significantly. The results thus suggest that a daily dosage of 2.5 g n-3 fatty acids does not enhance LDL susceptibility to oxidation, while retaining its hypotriacylglycerolemic effect.

Insulin action and glucose metabolism are improved by gemfibrozil treatment in hypertriglyceridemic patients.

The aim of this study was to determine whether gemfibrozil-mediated decrease in very low density lipoprotein triglyceride (VLDL-TG) concentration is accompanied by an improvement in overall glucose metabolism in hypertriglyceridemic patients. We assessed this hypothesis in 7 hypertriglyceridemic without (HTG) and in 11 hypertriglyceridemic with noninsulin-dependent diabetes mellitus (NIDDM-HTG) who followed three-months treatment either with the drug or with placebo. Placebo VLDL-TG concentrations in both HTG (3.82 +/- 0.92 mmol/l (mean +/- S.D.) vs. 3.91 +/- 1.01 mmol/l) and in NIDDM-HTG (6.62 +/- 3.93 mmol/l vs. 6.84 +/- 4.16 mmol/l) were not different from baseline values, whereas gemfibrozil decreased VLDL-TG in both groups (1.84 +/- 0.56 mmol/l, P < 0.001 for HTG, and 1.93 +/- 2.68 mmol/l, P = 0.013 in NIDDM-HTG). In both groups, gemfibrozil treatment was associated with an improvement in fasting plasma glucose levels (from 5.85 +/- 0.92 mmol/l to 4.87 +/- 0.40 mmol/l in HTG, P = 0.001, and from 11.47 +/- 2.92 mmol/l to 9.56 +/- 3.41 mmol/l in NIDDM-HTG, P = 0.042). In NIDDM-HTG, gemfibrozil treatment was associated with a significantly lower 2 h-postprandial plasma glucose level (9.87 +/- 3.63 vs. 13.09 +/- 3.62, P = 0.05). A significant decrease in fasting free fatty acids (FFA) level was observed during gemfibrozil treatment in both groups, whereas in NIDDM-HTG, a significant drop of these substrates was observed in both fasting and postprandial conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of dietary monounsaturated and polyunsaturated fatty acids on the susceptibility of plasma low density lipoproteins to oxidative modification.

Oxidized low density lipoproteins (LDLs) are thought to play an important role in atherogenesis. Nutritional and biochemical studies suggest that diet can modulate the susceptibility of plasma LDL to undergo oxidative degradation by affecting the concentration of polyunsaturated fatty acids and antioxidants in the lipoprotein particle. In the present study 11 healthy male volunteers underwent two diet phases. In one phase the diet was enriched in oleic acid (mono), while in the other it was high in linoleic acid (poly). Both diets lowered plasma total and LDL cholesterol contents. The sensitivity of plasma LDL to oxidation was estimated by challenging these lipoproteins with 2,2'-azobis(2-amidinopropane)dihydrochloride, a free-radical initiator. Although neither diet affected the antioxidant content of plasma LDL, the resistance to lipid peroxidation, measured after the consumption of antioxidants present in the lipoprotein, was higher during the mono phase. Indeed, the peroxidation rate of plasma LDL was inversely correlated with the oleic acid to linoleic acid ratio in the LDL particle. These results support the thesis that diets rich in monounsaturated fatty acids increase the resistance of plasma LDL to oxidative modification, independent of their content of antioxidants. This effect could lower the atherogenicity of these lipoproteins.

Carbohydrate and lipid metabolism in patients with non-insulin-dependent diabetes mellitus: effects of a low-fat, high-carbohydrate diet vs a diet high in monounsaturated fatty acids.

Nineteen patients affected by non-insulin dependent diabetes mellitus (NIDDM), in good glycemic control (fasting plasma glucose 7.2 +/- 0.3 mmol/L, glycosylated hemoglobin 6.3 +/- 0.2%), underwent three isocaloric dietary phases. In phases 1 and 3 the diet was rich in complex carbohydrates (Carbo) whereas in phase 2 it was rich in monounsaturated fatty acids (Mono). Plasma glucose concentrations were 7.1 +/- 0.3 and 7.2 +/- 0.3 mmol/L for the two Carbo phases and 7.5 +/- 0.4 mmol/L for the Mono phase (NS). Plasma total cholesterol values for the Carbo phases were 6.2 +/- 0.2 and 6.4 +/- 0.2 mmol/L, respectively, and 6.5 +/- 0.2 mmol/L on the Mono phase (NS). Similarly, no significant changes were noticed for plasma triglycerides and high-density-lipoprotein (HDL) cholesterol. Thus, both diets were well-tolerated and did not alter glucose homeostasis or worsen plasma lipid concentrations. Consequently, these results suggest that a wider dietary choice can be made available to NIDDM patients without producing unwanted side effects.

Delivery of the tumour photosensitizer zinc(II)-phthalocyanine to serum proteins by different liposomes: studies in vitro and in vivo.

Zn-phthalocyanine (Zn-Pc) incorporated into liposomes of different phospholipids has been incubated in vitro with human serum and administered i.v. to rabbits. In both cases, chromatographic and density gradient ultracentrifugation studies indicate that Zn-Pc is almost exclusively bound by the 3 major lipoprotein components of the plasma (VLDL, LDL and HDL). The amounts of Zn-Pc recovered from the different lipoprotein fractions reflect their relative concentration in the serum. The presence of 20% moles of cholesterol in liposomes of dipalmitoyl phosphatidylcholine (DPPC) optimizes the release of Zn-Pc to LDL. This fact is important for enhancing the selectivity of drug delivery to tumors since LDL display a preferential interaction with neoplastic cells.

Enhanced prevalence of red blood cell macrocytosis in psoriatic patients. A sign of ethanol abuse?

An enhanced prevalence of red blood cell macrocytosis without anaemia was found in 326 psoriatic patients as compared with 310 control subjects. The percentage of ethanol abusers was higher among the psoriatic patients. No difference in the prevalence of ethanol abuse was found when comparing psoriatic patients with controls who also had macrocytosis.

Increased proteolytic activity of erythrocyte membrane in spur cell anaemia.

In a case of 'spur cell anaemia' (SCA) a reduced esterified/free cholesterol ratio was found in plasma, in LDL and HDL fractions and an increased cholesterol/phospholipid (C/PL) molar ratio in erythrocyte membrane. Cation transport was normal with the exception of Li-Na counter-transport was decreased. An increased intrinsic membrane proteolytic activity (IMPA) was demonstrated by the generalized reduction or, sometimes, disappearance of protein bands on SDS-PAGE in patient ghosts when the proteolysis was allowed. This characteristic was found to be transferable to normal cells by incubation in SCA-plasma; moreover membrane C/PL molar ratio was augmented after incubation. Normal plasma was not able to normalize IMPA of SCA cells 'in vitro', even if it induced a remarkable decrease of membrane C/PL molar ratio. Nevertheless IMPA normalization did occur 'in vivo', when the SCA cells were exposed to therapeutic 'plasma exchange' (3.3 litre/week). The results suggest the following conclusions: (a) in our SCA patient there is an increased IMPA; (b) this feature, as well as membrane lipid alteration, is transferable to normal erythrocytes; (c) this case seems to demonstrate, for the first time in our knowledge, a modulating effect of plasma on IMPA in erythrocytes.

Lipoprotein binding to cultured aortic smooth muscle cells from normotensive and hypertensive rats.

Little is known about the pathophysiological mechanisms responsible for the higher incidence of atherosclerosis in hypertensive subjects. In view of the known atherogenic role of low-density lipoproteins (LDL), the aim of the present study was to evaluate possible differences in LDL binding to cultured aortic smooth muscle cells from normotensive and hypertensive rats. We studied the time-dependence and dose-dependence of LDL binding to both cell types. Low density lipoprotein binding to smooth muscle cells from the hypertensive rat was significantly higher than that to smooth muscle cells from the normotensive rat. This mechanism might explain the higher incidence of atherosclerotic lesions observed in hypertension.

Hematoporphyrin binding to cultured aortic smooth muscle cells from spontaneously atherosclerotic turkey.

Porphyrins are known to be accumulated in vivo by tumors and atherosclerotic plaques. We studied the interaction of cultured aortic smooth muscle cells (SMC) from spontaneously atherosclerotic Broad Breasted White Turkeys (BBWT) with free hematoporphyrin (Hp) and low density lipoprotein (LDL)-Hp complexes. A significantly higher binding of LDL-Hp to SMC as compared to free Hp was observed. These data indicate that porphyrin binding to vascular SMC represents a possible mechanism for porphyrin accumulation by atherosclerotic plaques. This process is mediated, at least in part, by LDL.

Apolipoprotein E polymorphism, serum lipids and occurrence of "double pre-betalipoproteinemia' (DPBL) in subjects from two different populations.

The association between apolipoprotein E phenotype and the presence of 2 electrophoretic populations of very low density (VLDL) lipoproteins from human sera, double pre-beta(VLDL)lipoproteinemia (DPBL), was studied in 2 groups of subjects, one from Italy and one from Finland. In both populations the prevalence of DPBL was significantly higher in subjects with E4/4 and E4/3 phenotypes than in the other phenotypes not containing the E4 isoprotein. This finding suggests that the presence of a structural variant of the apo E protein, the isoprotein E4, may be causally related to the appearance of DPBL phenomenon.

Role of high-, low- and very low-density lipoproteins in the transport and tumor-delivery of hematoporphyrin in vivo.

Free hematoporphyrin administered intravenously to healthy rabbits (1-28 mg/kg body weight) is bound by the 3 major lipoprotein components of plasma (VLDL, LDL and HDL) with different efficiency. In vitro-prepared complexes of hematoporphyrin (Hp) with lipoprotein fractions isolated from mouse serum have been injected intracardiacally into mice affected by MS-2 fibrosarcoma (1 mg of Hp per kg body weight). LDL appear to allow a more specific delivery of the complexed Hp to the tumor tissue as compared with HDL, VLDL or free Hp. The different behavior of VLDL, LDL and HDL as carriers of Hp in vivo is also discussed.