G. Giudici

Free radicals promote modifications in plasma high-density lipoprotein: Nuclear magnetic resonance analysis

The behavior of high-density lipoprotein (HDL) after free-radical-mediated oxidation was studied by incubating plasma HDL with chemical oxidizing systems (Cu++) in conditions similar to those used for low-density lipoprotein (LDL) chemical oxidation. Nuclear magnetic resonance (NMR) spectroscopy (1H and 31P) was used to evaluate the degree of oxidation and to characterize the oxidized products. The almost complete loss of polyunsaturated systems together with an appreciable decrease in choline peak demonstrates large-scale HDL-lipid degradation. The appearance of epoxide systems on fatty chains and the identification of oxidized cholesterol derivatives as cholesterol 5 alpha,6 alpha-epoxide, 5 beta,6 beta-epoxide, 7-keto, and 25-hydroxy confirm this picture. Phospholipid analysis indicates an alteration of the phospholipid profile in lyso-phosphatidylcholine (Lyso-PC) production and the disappearance of phosphatidylethanolamine (PE). This study shows that HDL is extensively degraded although there are no large variations in the classical oxidative monitors, lipid hydroperoxide (LPO) and thiobarbituric acid reactive substance (TBARS). Our results suggest that HDL is significantly modified when submitted to an oxidative process.

Restriction-fragment-length polymorphisms in the A-I-C-III gene complex occurring in a family with hypoalphalipoproteinemia

Two restriction-fragment-length polymorphisms in the apolipoprotein A-I-C-III gene complex were defined by digestion with PstI and SacI in a family with hypoalphalipoproteinemia. These polymorphisms established a PstI + /SacI - haplotype which may constitute a linkage marker for this condition within the family.

Chronic continuous intraperitoneal insulin infusion (CIPII) in type I diabetic patients non-satisfactorily responsive to continuous subcutaneous insulin infusion (CSII).

SummarySix unstable C-peptide negative type I diabetic patients who had been previously treated with continuous subcutaneous insulin infusion (CSII) for at least one year without achieving satisfactory metabolic control, were admitted to this study and switched to continuous intraperitoneal insulin infusion (CIPII). The results obtained with the two treatments have been compared from the metabolic and clinical points of view. CIPII produced a decrease in HbA1c (p<0.05), in MAGE value (p<0.005), in the percentage of blood glucose determinations above 14 mmol/l (p<0.05) and below 3.9 mmol/l (p<0.05); an increase in serum cholesterol, and a decrease in HDL-cholesterol (p<0.05) due to a reduction of the HDL2 fraction (p<0.01). A mean body weight reduction of 3 kg was observed during CIPII (p<0.01), not related to dietary changes or to a reduction of the daily insulin dose. Twenty-four hour metabolic profiles during CIPII showed lower mean plasma glucose (p<0.001), serum free insulin (p<0.001), blood β-OH-butyrate (p<0.001), and higher serum glycerol (p<0.001) as compared to CSII. It is concluded that CIPII may be of clinical value in the out-patient management of unstable type I diabetic patients, and that metabolic modifications induced by CIPII are not limited to changes in glucose utilization and production, but include changes in triglyceride, cholesterol and lipid metabolism which may have clinical relevance.

Determination of Lp(a) and APO(a) in an Italian population

SummaryPlasma lipoprotein(a) [Lp(a)] levels were determined in an Italian population subdivided according to age and sex. The distribution of plasma Lp(a) levels was highly skewed, with 75% of the subjects having less than 10 mg/dl. No significant differences were found in the plasma Lp(a) levels of the two age groups, but women had significandy higher levels than men. There was no significant correlation between Lp(a) levels and the other lipid and lipoprotein parameters studied, with the exception of a weak correlation between Lp(a) levels and both total cholesterol and low density lipoprotein-cholesterol in younger women. Apoprotein(a) phenotyping was performed in about one-third of the population; an inverse relationship between the molecular weight of the different isoforms and plasma concentrations of Lp(a) was observed.

NMR analysis of low-density lipoprotein oxidatively modified in vitro

Human plasma low density lipoprotein has been oxidized at different stages in vitro and analysed by 1H, 13C, and 31P NMR spectroscopy and by biochemical methods. Information was obtained on: a) structure mobilities of lipids and on lipid-protein interactions; b) conjugated and oxo-dienes; c) polyunsaturated/monounsaturated fatty acid chains; d) lysophosphatidylcholine production. The results show that the NMR approach is particularly useful for the assessment of structural modification in oxidized LDL.