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Biomedical subjects

G Cazzolato

Publications and source records attributed to G Cazzolato.

At least 73 records · Page 4Linked to original sources
PubMedDate not supplied

Lipids, lipoproteins and apolipoproteins in type 1 (insulin-dependent) and type 2 (non-insulin-dependent) diabetes mellitus.

Total plasma cholesterol, triglycerides, VLDL-C, VLDL-TG, HDL-C and the apoproteins A-I, A-II, B and D were measured in 111 male non-obese diabetic patients and in 90 male control subjects of similar age and body weight distribution. Forty-eight patients had Type 1 (insulin-dependent diabetes) and 63 had Type 2 (non-insulin-dependent diabetes); all were in stable metabolic control while following an appropriate diet and therapy with insulin or oral hypoglycemic agents. HDL-C, apoA-I, apoB and the apoA-I/apoA-II ratio were significantly increased in the Type 1 patients, whereas the VLDL-C/VLDL-TG and LDL-C/apoB ratios were decreased significantly. Type 2 diabetics showed low HDL-C and low apoA-I/apoA-II ratio, while the values of apoA-I, A-II, D and the VLDL-C/VLDL-TG ratio were significantly higher than in controls. Type 1 diabetics in 'fair' metabolic control presented higher values of TG, VLDL-C, VLDL-TG and apoB than patients in 'good' control: lower values of apoA-I and of the ratios apoA-I/apoA-II, apoA-I/apoB and LDL-C/apoB were recorded in the same subgroup. In Type 2 diabetics no significant differences were observed according to metabolic control, with the exception of a higher apo-D value in subjects in 'fair' control. The data obtained support the view that good metabolic control may be important for the prevention of a relevant derangement of lipoprotein components, particularly in Type 1 patients.

Adult↗
PubMedDate not supplied

Distribution and concentration of apolipoprotein E in high and low density lipoproteins.

An electroimmunoassay of apolipoprotein E (Apo E) in total human plasma and in the supernatant following precipitation with sodium phosphotungstate in the presence of MgCl2 of the apolipoprotein B (Apo B)-containing lipoproteins is described. The assay is specific and sensitive enough to record also low levels of Apo E found in isolated lipoprotein fractions. In 30 normal male subjects, the method gave a total plasma Apo E concentration of 6.67 +/- 1.92 mg/dl and a HDL Apo E concentration of 2.58 +/- 0.91 mg/dl. Total Apo E is positively correlated with total plasma triglycerides. The values of Apo E in the lipoproteins obtained by ultracentrifugation were lower than the corresponding values obtained by a precipitation procedure, with a mean Apo E loss of 12.1% in the low density lipoproteins (VLDL + LDL) and of 34.3% in HDL. After ultracentrifugation, a substantial amount of Apo E was detected in the d greater than 1.210 g/ml fraction. The proposed method allows to study the Apo E concentration and distribution between low and high density lipoproteins in large samples, avoiding the problems connected with high salt concentrations and centrifugal forces.

Apolipoproteins↗
PubMedDate not supplied

Concentration, composition and apolipoprotein B species of very low density lipoprotein subfractions from normolipidemic and hypertriglyceridemic humans.

Lipoproteins in the d less than 1.006 g/ml density range obtained form 13 healthy normolipidemic subjects and from 15 patients affected by primary endogenous hypertriglyceridemia after 14-h fasting were subfractionated by filtration in Biogel A-15 M columns. The mass values and chemical composition of very low density lipoprotein (VLDL) subfractions 1 and 2 thus obtained were studied. In each subfraction the behavior of apolipoprotein B (Apo B) was tested by sodium dodecyl-sulfate polyacrylamide gel electrophoresis. VLDL2 was higher and richer in cholesterol and proteins than VLDL1, while the percentage content of triglycerides was lower. In hypertriglyceridemic patients both VLDL1 and VLDL2 were higher than in normolipidemic subjects, the difference being particularly evident for VLDL1. In both VLDL1 and VLDL2 of nearly all the subjects studied the presence in electrophoretic gels of a large Apo B-100 band and of a minor Apo B-48 band with the appropriate mobility of lymph chylomicrons was detected. The Apo B-100/Apo B-48 ratio was about 6 in VLDL1 and 24 in VLDL2. A trend of a reduced Apo B-100/Apo B-48 ratio was observed in VLDL1 of hypertriglyceridemic patients.

Adult↗
PubMedDate not supplied

Familial hyper-HDL-(a)-cholesterolemia.

In one family the mother, two children and a maternal aunt showed a hypercholesterolemic state characterized by a unusually high percentage of cholesterol in ultracentrifugally-recovered HDL-(a)-LP. An intensely stained a-band was present in all these subjects both in plasma and in ultracentrifugal fraction, with d greater than 1063. Symptoms or signs due to the hypercholesterolemic state were not present. The father was affected by Type IIA hypercholesterolemia. This lipid defect was also present in one of the two children.

Adult↗
PubMedDate not supplied

Probucol protects low-density lipoproteins from in vitro and in vivo oxidation.

Twelve patients with primary hypercholesterolemia were treated for 12 weeks with probucol (500 mg b.i.d.). For each patient low density lipoproteins (LDL), isolated by ultracentrifugation were subfractionated by ion exchange high resolution chromatography in order to evaluate the content of a more electronegatively charged LDL (LDL-), a small subfraction that probably represent a circulating oxidatively modified lipoprotein. The treatment induced a 17% reduction of total LDL and 43% reduction of LDL-. By thin layer chromatography the probucol content in LDL- was a quarter of that in normally charged LDL. Under basal conditions, native LDL incubated for 24 h with 3 microM copper sulphate shows a net increase in electrophoretic mobility, an increase in relative fluorescence intensity and a reduction in vitamin E content, thus indicating peroxidative damage. After treatment with probucol, no significant changes of electrophoretic mobility, fluorescence and vitamin E content are detectable. LDL isolated from patients treated with probucol thus become resistant to oxidation by copper ions. The observed reduction of LDL- after treatment with probucol, confirms in vivo the antioxidant role of the drug and support the hypothesis that circulating LDL- may be linked to an oxidative process occurring in vivo.

Adult↗
PubMedDate not supplied

Apoprotein B-48 is a constant finding in very low density lipoproteins of humans.

The results of this study indicate that very low density lipoprotein (VLDL) from the plasma of fasting normolipidemic or slightly hypertriglyceridemic subjects contains two apo B species. In SDS gel electrophoresis, the VLDL shows the presence of a major band corresponding to low density lipoprotein (LDL) apo B (apo B-100) and a minor band with the appropriate mobility of the lymph chylomicron apo B (apo B-48). The reactivity of monoclonal antibodies directed against opportunely selected human apo B suggests that the protein with the lower molecular weight corresponds to apo B-48. This finding was confirmed by using immunoadsorbants and affinity chromatography with monoclonal antibodies that react only with apo B-100. Through this method, VLDL were separated into two fractions: one that had only apo B-100 and one with both apo B-100 and apo B-48. Hepatic and intestinal VLDL may constitute different particles. The ratio of apo B-100 to apo B-48 in VLDL decreased as the mass of fasting plasma VLDL increased. This may improve our understanding of the metabolism of triglyceride-rich lipoproteins. The investigation of the new subspecies of apo B may be relevant in understanding the atherogenetic process and better defining the hyperlipidemic states.

Adult↗
PubMedDate not supplied

Presence of a modified low density lipoprotein in humans.

Low density lipoproteins (LDL) collected from 18 fasting humans were subjected to ion exchange chromatography on DEAE Sepharose. By this procedure, a LDL subfraction was isolated with an electric charge more negative than the LDL bulk. This LDL appeared to be mainly characterized by low phospholipid content, high free cholesterol and protein content, low esterified/free cholesterol ratio, and a high content of conjugated dienes, particularly of cholesterol esters. This subfraction, in an amount ranging from 5% to 20% of total LDL, was characterized by the presence of apo B-100 and protein aggregates that were reactive to anti-apo B monoclonal antibodies. Electron microscopy showed the more electronegative LDL to be heterogeneous in size with a tendency to aggregate. This LDL had low binding capacity with high affinity receptors of fibroblasts and low immunoreactivity with the monoclonal antibodies that recognize the receptor binding domain of apo B. Finally, the incubation of this LDL subfraction with cultured macrophages led to a higher increase in cellular cholesterol in spite of a lower rate of uptake as compared to the LDL bulk and to acetyl-LDL. The more electronegative LDL subfraction that we isolated for chemico-physical behavior and conjugated diene content may represent the peroxidized aliquot of human LDL.

Adult↗