Goretta Baldo

Relationship between triglyceride-rich lipoprotein (chylomicrons and VLDL) and HDL2 and HDL3 in the post-prandial phase in humans.

In order to evaluate the relationship between triglyceride-rich lipoproteins (chylomicrons and VLDL) and HDL during alimentary lipaemia, 12 healthy volunteers, 6 male and 6 female (aged 20--40 yrs), were studied. Cholesterol, phospholipid, triglyceride and protein were evaluated in whole serum, VLDL, LDL and HDL (successively subfractionated in HDL2 and HDL3). Blood samples were collected in a fasting state, 4.5 and 9 h after a 1500 calorie meal (20% protein, 40% carbohydrate, 40% fat). A striking increase in triglyceride-rich lipoproteins after 4.5 h was observed in both sexes, but was more pronounced in males. An increase in phospholipid and triglyceride as well as a slight reduction in cholesterol was evident in HDL after 4.5 h. At the same time both lipids and proteins were decreased in HDL3 and increased in HDL2. This phenomenon is more evident in females, who showed a significantly higher basal HDL2 level. These results suggest a possible metabolic relationship in the post-prandial phase between triglyceride-rich lipoproteins and HDL, and an inverse correlation between HDL2 and HDL3.

Familial lipoprotein lipase and apolipoprotein C-II deficiency Lipoprotein and apoprotein analysis, adipose tissue and hepatic lipoprotein lipase levels in seven patients and their first degree relatives

Plasma lipids, lipoproteins, tissue lipoprotein lipase (LPL) and hepatic lipase (H-TGL) were studied in 7 patients with familial hyperchylomicronemia from four different families. Their first-degree relative were also studied. The patients were heterogeneous for the genetic defect; LPL activity was absent in five patients (LPL deficiency) but normal in two. However, these two did not have apo C-II, the physiological activator of LPL (C-II deficiency). There were no significant differences in the clinical picture between patients with LPL deficiency and C-II deficiency. In both mutants, marked hypertriglyceridemia was due to an accumulation of lipoproteins of density less than 1.006 g/ml. The LDL fraction was very reduced and abnormal in composition, presenting a CH/TG ratio of 0.5. The plasma apolipoprotein B (apo B) level was low (67 +/- 5.5 mg/dl) and was transported mainly in the VLDL fraction (26 +/- 3.2 mg/dl) rather than in the LDL fraction (15 +/- 1.4 mg/dl). Very low levels of cholesterol and apolipoprotein A-I in HDL subfractions HDL2 and HDL3 were also recorded. Only 3 out of the 24 first-degree relatives of patients with LPL deficiency showed even a small increase in plasma triglycerides, but 15 had low or low to normal LPL values. H-TGL levels were normal in all subjects. The 4 first-degree relatives of C-II deficiency patients showed normal levels of plasma lipids. LPL and H-TGL, and 2 children of 1 patient showed normal distribution of apo C peptides in their VLDL. A block in chylomicron catabolism, due to the absence of LPL or apo C-II, may lead to a massive accumulation of lipoproteins with a density less than 1.006 g/ml, and a drastic reduction in the LDL and HDL fractions. Low LPL values in the first-degree relatives of LPL deficiency patients might represent a biochemical marker for healthy carriers of LPL deficiency.

A comparative study of serum and synovial fluid lipoprotein levels in patients with various arthritides.

UNLABELLED The aim of this study was to investigate apolipoprotein (apo) A-I, apo B, lipoprotein (Lp) (a), HDL-cholesterol (C), LDL-C, triglycerides (TG) and total cholesterol (TC) values in the serum and synovial fluid (SF) of untreated rheumatoid arthritis (RA), psoriatic arthritis (PsA), and osteoarthritis (OA) patients. METHODS Paired SF and serum samples were collected simultaneously from 14 patients with RA, 14 with PsA, and 16 with OA and tested for apo A-I, apo B, HDL-C, LDL-C, Lp(a), TC and TG. Serum C reactive protein (CRP) and amyloid A (SAA) levels were also determined. RESULTS The inflammatory arthritis patients had higher SF lipid levels with the exception of HDL. Reflecting increased synovial permeability, the lipid SF/serum ratio was always higher in RA and PsA with respect to OA patients. The positive correlation between serum and SF apo A-I, apo B, HDL-C, TG, and Lp(a) levels confirmed that there is lipoprotein diffusion into the SF. RA and PsA patients had lower concentrations of all serum lipids except for Lp(a) with respect to OA patients. The levels in the RA patients were similar to those in healthy matched controls, while the PsA patients had significantly lower apo A-I and HDL levels and higher apo B and LDL values. CONCLUSIONS Lipid diffusion into the joint cavity, which largely depends on the degree of inflammation, may contribute to modulating local inflammatory processes.

Carotid artery lesions in patients with nondiabetic chronic renal failure

Atherosclerotic complications are the leading cause of death in chronic renal failure (CRF) patients. Therefore, we wished to investigate the prevalence of carotid artery lesions (CALs) in these subjects. Two groups were evaluated by high-resolution echo Doppler: group 1 included 103 patients (68 males and 35 females) affected by nonnephrotic CRF and group 2 included 100 control subjects (60 males and 40 females). The prevalence of hypertension was 84% in both groups. The exclusion criteria included diabetes mellitus and symptoms of cerebrovascular disease. In the two groups we evaluated clinical history, physical examination, total cholesterol, triglycerides, fibrinogen, blood cell counts, blood urea nitrogen, creatinine, 24-hour proteinuria, and urine analysis. In group 1 patients the following lipid profile parameters were also evaluated: low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, lipoprotein(a), ApoAI, ApoAII, and ApoB. Group 1 had higher triglycerides and fibrinogen than group 2. A lower body mass index was found in group 1 than in group 2. The prevalence of CALs was significantly higher in the CRF patients than in the control subjects (62% v 47%; P = 0.04). The difference between the two groups was more striking among normotensive patients (62% v 19%; P = 0.03). All CRF patients affected by peripheral arterial disease and 86% of those having coronary artery disease had associated CALs. In CRF patients the severity of CALs was positively correlated to age, white blood cell count, triglycerides, and fibrinogen. Nondiabetic CRF patients have a higher prevalence of carotid artery lesions than control subjects. Several factors besides hypertension, including lipids, blood coagulation, and leukocytes, could contribute to the accelerated atherosclerosis of CRF patients.

Characterization of hyperlipidemia m two patients with analbuminemia

The results of plasma lipid and lipoprotein analysis in two related patients, brother (R.U.) and sister (R.R.) with analbuminemia, and three first-degree relatives (parents and sister) are reported. Both patients showed a remarkable increase in cholesterol and phospholipid levels, and there was a corresponding increase in serum apo B and apo A-I. This hyperlipidemia is due to a selective increase in LDL and HDL concentrations. R.U. showed an increase in both HDL2- and HDL3-cholesterol, R.R. only in HDL3-cholesterol. VLDL concentration was reduced in R.U. and normal in R.R. The plasma lipoprotein electrophoretic pattern did not correspond to any of the phenotypes in Fredricksons classification. Composition of the different lipoprotein fractions was normal in the patients and family members. Serum FFA level in R.R. was very low. An increase in the plasma protein fractions, particularly the transport fractions, was confirmed in both patients. The possible pathophysiology of the hypercholesterolemia in these patients is discussed. Unlike other reported cases, clinical signs of atherosclerotic complications were absent.

Long-term trial with colestipol plus clofibrate in familial hypercholesterolemia.

Twenty subjects with familial hypercholesterolemia (12 Type IIa and 8 Type IIb), previously treated with Colestipol for 16 months, were subjected to therapy with Colestipol (15 g/day) + clofibrate (2 g/day) for 15 months. During the second treatment period these patients continued to follow the isocaloric hypocholesterolemic diet initiated during the original trial. In Type IIa patients, the association of these drugs enhanced the decrease in plasma cholesterol levels. The total mean decrease was -40 +/- 17 mg/dl (P less than 0.05). In Type IIb patients, on the other hand, the association of clofibrate with Colestipol induced an increase in plasma cholesterol levels. The total mean increase was +24 +/- 7 mg/dl (P less than 0.05). A markedly significant decrease in plasma triglyceride levels was observed in this group (- 107 +/- 30; P less than 0.01). These results seem to indicate that, in Type IIa, clofibrate increased the resins hypocholesterolemic effect. In Type IIb, on the other hand, the association of these drugs did not seem to be indicated since a marked hypotriglyceridemic effect was accompanied by an increase in plasma cholesterol levels. These results are briefly discussed in the light of recent data obtained on the effects of Colestipol and clofibrate on lipoprotein metabolism.

Characterization with zonal ultracentrifugation of low-density lipoproteins in type V hyperlipoproteinemia.

Low-density lipoproteins (density = 1.019-1.063 g/ml) were isolated in 10 subjects with type V hyperlipoproteinemia by ultracentrifugation in a zonal rotor under rate flotation conditions. Plasma LDL concentrations in these patients were extremely reduced, as well as being heterogeneous, and two different subclasses consisting of LDL2 (density = 1.019-1.045 g/ml) and LDL3 (density = 1.045-1.063 g/ml) were observed. LDL2 and LDL3 have similar electrophoretic mobilities in beta position in agarose gel, and their diameters, calculated from gel filtration studies, were inversely proportional to their densities. LDL2 and LDL3 have a mean hydrated density of 1.034 and 1.054 g/ml, respectively. In comparison with normal LDL2, the LDL2 and LDL3 of hypertriglyceridemic subjects are particularly rich in triacylglycerols and poor in cholesteryl esters and free cholesterol, while they have an increasing amount of proteins. The protein moiety is composed almost exclusively of apolipoprotein B-100 in IDL, LDL2 and LDL3 ; in addition, IDL also contain apolipoprotein C peptides. This characterization of LDL heterogeneity in type V hyperlipoproteinemia should be considered in interpreting kinetic data in human normal and pathological lipid metabolism and in evaluating the atherogenic risk of hypertriglyceridemia.

Altered surfactant synthesis and function in rats with diet-induced hyperlipidemia

Altered lung function in hyperlipidemic patients has been reported by many authors. An alteration of surfactant synthesis has been suggested. Isolated lungs of rats rendered hyperlipidemic by suitable diets display an increased distensibility at maximal inflation and a higher degree of alveolar stability during deflation. These alterations are related to modifications of surfactant properties. Lung lavage fluid obtained from hyperlipidemic rats displays an increase in percent content of phosphatidylglycerol and a decrease of phosphatidylethanolamine. The percent content of phosphatidylglycerol correlates with the circulating levels if free fatty acids (FFA). It is suggested that FFA might affect the activity of enzymes operating in lung phospholipid synthesis. The reported increase of surfactant phosphatidylglycerol might explain the increment of alveolar stability observed in hyperlipidemic rats.

Glycosylated hemoglobin in endogenous hypertriglyceridemia

SummaryFifty out-patients with endogenous hypertriglyceridemia were submitted to glycosylated hemoglobin (GHb) and glucose tolerance assessment. Fifteen had normal glucose tolerance (NGT), 15 had impainred glucose tolerance (IGT) and 20 had non-insulin-dependent diabetes mellitus (NIDDM). GHb was 6.3% in NGT, 7.3% in IGT and 8.11% in NIDDM and was significantly correlated to fasting and post-prandial plasma glucose (p<0.001) in NIDDM group and to peak, area (p<0.001) and 2-h plasma glucose levels (p<0.05) of OGTT in the NGT and IGT groups. Out of the 15 IGT subjects only 6 had GHb levels above the control range, while 9 had normal GHb values. These data show that also in hyperlipemic subjects GHb values are related to glucose tolerance, and suggest that GHb evaluation alone is not sufficient for the diagnosis of impaired glucose tolerance. In order to evaluate whether plasma turbidity can affect GHb dosage, GHb was evaluated in 10 hyperlipemic subjects with various degrees of hypertriglyceridemia both in the presence (whole blood hemolysate) and absence (isotonic saline hemolysate) of plasma triglycerides. The results show that, with our method, plasma turbidity does not affect GHb evaluation.