PubMed Health⌕ Search

Biomedical subjects

L Calabresi

Publications and source records attributed to L Calabresi.

53 records · Page 3Linked to original sources
PubMed1991

Inhibition of antipyrine metabolism by low-dose contraceptives with gestodene and desogestrel.

To examine the effects of the two newest monophasic oral contraceptives on liver microsomal drug metabolism, plasma kinetics and urinary metabolite excretion of antipyrine, a model substrate for liver microsomes, were evaluated. Plasma lipid and lipoprotein levels, and in particular the high-density lipoprotein subfractions, were also monitored in view of their apparent regulation by a P450-dependent system. Ten healthy volunteers were treated with each contraceptive for a period of 3 months in a crossover trial. Both contraceptives significantly reduced antipyrine clearance by 34.6% (gestodene) and 43.3% (desogestrel) by impairing the oxidative metabolism, particularly to the 4-hydroxy and 3-hydroxymethyl metabolites, with little difference between the two associations. In addition, with both a comparable highly significant rise of plasma triglyceride levels, apolipoproteins A-I and A-II and the high-density lipoprotein-3 subfraction was observed. Treatment with these new monophasic contraceptives may reduce the metabolism of concomitantly given drugs undergoing oxidative transformations.

Adult↗
PubMed1991

Predictability of low-density lipoprotein levels during apheretic treatment of hypercholesterolaemia.

The efficiency and efficacy of low-density lipoprotein (LDL) apheresis performed with a dextran sulphate cellulose (DSC) regenerating unit were tested in five familial hypercholesterolaemic patients. LDL apheresis was repeated four times at both bi-weekly and weekly intervals, processing one plasma volume each time. The efficiency of the procedure (i.e., the extent of lipoprotein removal) was nearly identical with both schedules. Efficacy parameters, i.e., decreases of plasma total and LDL cholesterol (TC and LDL-C) and apo B, were highly correlated (r greater than 0.96) with preapheresis levels, allowing an accurate prediction of the absolute lipid removal in the single individual. Plasma triglycerides, high-density lipoprotein cholesterol, apo A-I and apo A-II recovered rather rapidly, reaching 91-96% of the pre-apheresis values in 48 hours; the recovery of TC, LDL-C and apo B was much slower, with a relatively rapid early phase (80% recovery after about 7 days) followed by a successive slower rise. This pattern was highly reproducible in the single patient, allowing the definition of a simple mathematical model for an accurate (error less than 20%) prediction of the individual process. Based on this model one can design the treatment schedule necessary to maintain lipid levels within the desired range in the single individual. The hypolipidaemic efficacy of DSC apheresis appears, otherwise, not to be dependent upon the procedure per se, but on other individual factors, e.g. the amount of removable lipoproteins and the rate of lipid recovery; both can be predicted with sufficient accuracy.

Apolipoproteins↗
PubMed1990

Apolipoprotein AIMilano. Disulfide-linked dimers increase high density lipoprotein stability and hinder particle interconversion in carrier plasma.

The in vitro metabolism of high density lipoproteins (HDL) in carriers of the apolipoprotein AIMilano (apoAIM) mutant was investigated during incubation of whole plasma and isolated lipoprotein fractions. A reduced cholesterol esterification (16.5 versus 25.0% for controls) and a decreased exchange of lipids between HDL and lower density lipoproteins was observed during incubation (6 h at 37 degrees C) of AIM plasma. Control HDL3 were converted to larger, faster-floating HDL particles, whereas only a fraction of AIM HDL3 followed the same pathway. Incubations were also carried out by mixing HDL3 from controls and AIM carriers with a lipoprotein-depleted plasma fraction in the presence of triglyceride-rich particles isolated from Intralipid. AIM HDL3 again showed a reduced capacity for lipid exchange; some HDL3 particles followed a "normal" conversion to faster-floating, larger HDL, whereas the small AIM HDL3 were not modified, indicating that AIM HDL3 are a mixture of metabolically functional and nonfunctional particles. Following transformation of the apoAIM homo- and heterodimers into their normal counterparts, i.e. monomeric apoAI and -AII, by reduction and carboxamidomethylation of AIM HDL3, the modified HDL3 behave like control HDL3 during incubation with lipoprotein-depleted plasma and triglyceride-rich particles. The presence of AIM dimers is most likely responsible for the increased HDL3 stability in the AIM carriers, indicating that apolipoprotein composition plays a major role in HDL particle interconversion.

Apolipoprotein A-I↗
PubMed1990

Apolipoprotein AIMilano. Partial lecithin:cholesterol acyltransferase deficiency due to low levels of a functional enzyme.

The cholesterol esterification process was analyzed in 19 carriers of the apolipoprotein AIMilano (AIM) variant and in 19 age-sex matched controls by measuring lecithin:cholesterol acyltransferase (LCAT) mass, activity (i.e., cholesterol esterification with a standard proteoliposome substrate) and cholesterol esterification rate (i.e., cholesterol esterification in the presence of the endogenous substrate). The AIM subjects had lower LCAT mass (3.30 +/- 0.85 micrograms/ml), activity (71.1 +/- 36.4 nmol/ml per h) and cholesterol esterification rate (23.6 +/- 12.5 nmol/ml per h) compared to controls (5.22 +/- 0.74 micrograms/ml, 121.6 +/- 54.6 nmol/ml per h and 53.6 +/- 29.9 nmol/ml per h, respectively). The specific LCAT activity, i.e., LCAT activity per microgram of LCAT, was similar in the two groups, indicating that the LCAT protein in the AIM carriers is structurally and functionally normal. However, the specific cholesterol esterification rate was 23% lower in the AIM subjects (8.03 +/- 6.01 nmol/h per microgram) compared to controls (10.49 +/- 5.86 nmol/h per microgram; P less than 0.05). The capacity of HDL3, purified from both AIM and control plasma, to act as substrates for cholesterol esterification was similar, thus suggesting that other mechanism(s) may be in play. Carriers with a relative abundance of abnormal, small HDL3b particles had the most altered cholesterol esterification pattern. Upon evaluating all AIM subjects, a complex relationship between HDL structure, plasma lipid-lipoprotein levels and cholesterol esterification emerged, making the AIMilano condition a unique model for the study of the mechanisms regulating the cholesterol esterification-transfer process in man.

Adolescent↗
PubMed1990

Influence of serum triglycerides on the HDL pattern in normal subjects and patients with coronary artery disease.

The distribution and structure of high density lipoprotein (HDL) subfractions were examined by rate zonal ultracentrifugation in 200 consecutive subjects, 86 of whom showed a stable hypertriglyceridemia, 22 with coronary artery disease. Among the remaining 114 normotriglyceridemic subjects, 75 were healthy and 39 had coronary disease. The serum levels of the HDL2 subfraction were reduced by 22% in the 39 normotriglyceridemic coronary patients, and by 21% in the whole group of hypertriglyceridemic subjects. No difference in the HDL3 levels was found in any of the studied group. There was a clear negative correlation between HDL2 levels and triglyceridemia in the case of healthy people, not in coronary patients. By contrast, triglyceridemia was negatively correlated with the HDL3 flotation rate, both in healthy subjects and coronary patients at all triglyceride levels. Compositional data indicate that in hypertriglyceridemic subjects, HDL2 levels are reduced because of an enhanced transfer-exchanged process between the enlarged VLDL pool and HDL; in contrast, in coronary patients, a defective maturation of the HDL3 particle is the most likely underlying mechanism. Both in hypertriglyceridemic individuals, as well as in coronary patients, the HDL subfraction distribution is rather similar and drastically different from that of normotriglyceridemic healthy subjects. The mechanisms of the two conditions are probably different and, whereas a low concentration of HDL2 is definitely a major risk factor for normotriglyceridemic individuals, in the case of hypertriglyceridemics other factors may come into play in the final determination of the coronary risk.

Adult↗
PubMed1990

Comparison of the lipoprotein and hemostatic changes after a triphasic and a monophasic low dose oral contraceptive in premenopausal middle-aged women.

Metabolic and hemostatic effects of 2 low dose oral contraceptives (OCs), a triphasic (ethinylestradiol + (-)-norgestrel) and a monophasic (ethinylestradiol + desogestrel) preparation, were compared in a cross-over trial in fertile women over 35 years of age. Both combinations moderately affected plasma lipids, with 17-24% increases of total triglyceridemia. Triglycerides accumulate in low density lipoproteins, thus suggesting the possible formation of an atherogenic lipoprotein particle. Only the monophasic preparation increased high density lipoprotein (HDL)-cholesterol levels significantly, with a rise in HDL3 mass and cholesterol. OC treatment led to slight changes in HDL2 and HDL3 structure, with a rise of the cholesteryl ester and triglyceride contents, indicative of a stimulated cholesterol esterification and reverse transport. Changes in the hemostatic indexes (fibrinogen, antithrombin III and protein C) were negligible. The new low dose OCs, even when prescribed to relatively older women, affect to a relatively small extent lipid/lipoprotein metabolism, with the exception of changes in the low density lipoprotein composition.

Adult↗
PubMed1988

Changes in high-density lipoprotein subfraction distribution and increased cholesteryl ester transfer after probucol.

The effects of probucol (500 mg twice daily) on high-density lipoprotein (HDL) subfractions and cholesteryl ester transfer from HDL to lower density lipoproteins were tested in a series of patients with Type II hypercholesterolemia. In this placebo-controlled crossover trial, patients received probucol or placebo for 8 weeks, then switched to the other agent for another 8 weeks. Probucol significantly lowered total, low-density lipoprotein and HDL cholesterol levels. HDL subfractions, separated by rate zonal ultracentrifugation, showed a dramatic reduction in HDL2, whereas changes in HDL3 were not significant. Both subfractions eluted at a characteristically lower volume, indicating a reduced flotation rate. These findings were confirmed by gradient gel electrophoretic separation, which showed a typical reduction or disappearance of HDL2b particles and the prevalence of particles in the HDL3a-HDL3b electrophoretic range in almost all patients. After treatment, cholesteryl ester transfer from HDL to lower density lipoproteins was significantly increased in all patients. These data suggest that probucol may accelerate HDL particle conversion, leading to improvement in reverse cholesterol transport from the periphery to the liver, through HDL and very low density lipoprotein.

Carrier Proteins↗
PubMed1988

Apheretic treatment of severe familial hypercholesterolemia: comparison of dextran sulfate cellulose and double membrane filtration methods for low density lipoprotein removal.

The two more widely available techniques for the extracorporeal removal of low density lipoproteins (LDL), dextran sulfate cellulose column and double membrane filtration, were comparatively tested in severe familial hypercholesterolemic patients, both acutely and during a continued 3-month treatment. The selective dextran sulfate procedure removed close to 60% of LDL and 16% of high density lipoproteins (HDL) upon each apheresis, vs. 42% and 32%, respectively, in the case of the semi-selective double membrane filtration. Upon long term biweekly treatments, LDL-cholesterol (LDL-C) decreased, with the selective procedure, from a pre-treatment level of 406.0 +/- 40.7 mg/dl to a value fluctuating between 295.4 +/- 33.8 mg/dl and 116.9 +/- 22.0 mg/dl (highest vs. lowest levels) whereas, in the case of double membrane filtration, LDL-C levels ranged between 334.8 +/- 39.8 mg/dl and 192.3 +/- 49.9 mg/dl. HDL-cholesterol levels were somewhat raised, to a higher extent with dextran sulfate apheresis. The LDL/HDL-cholesterol "atherogenic ratio", decreased from a pre-treatment value of 10.27 +/- 3.04 to values ranging between 3.61 and 6.82 with dextran sulfate and between 6.70 and 7.68 with double membrane plasmapheresis.

Adult↗
PubMed1988

Alterations in the HDL system after rapid plasma cholesterol reduction by LDL-apheresis.

Changes in high density lipoprotein (HDL) subfraction structure and composition were analyzed during and after extracorporeal removal of apo B containing lipoproteins in seven familial hypercholesterolemic (FH) patients. After the apheretic procedure, carried out with dextran-sulfate-cellulose columns, the plasma levels of very low density lipoproteins (VLDL), low density lipoproteins (LDL), and HDL decreased by 72%, 50%, and 19%, respectively. The free cholesterol to esterified cholesterol ratio in plasma increased, with a 26% drop in the lecithin:cholesterol acyl transferase (LCAT) activity. In the ensuing 24 hours, VLDL, HDL, and LCAT activity approached the pretreatment levels. During this phase, possibly as a consequence of increased cholesterol esterification and exchange of cholesteryl esters for triglycerides between HDL and VLDL, HDL2a particles were detected in plasma. However, these metabolic changes did not result in clearcut modifications in the HDL2-HDL3 subfraction distribution. These findings clearly demonstrate that rapid changes in the plasma VLDL-LDL levels affect several processes involved in the HDL metabolism, but confirm that the HDL system, in spite of a considerable plasticity, displays a marked stability of the HDL2-HDL3 subfraction distribution.

Adolescent↗
PubMed1988

Alterations in high-density lipoprotein subfractions during postprandial lipidaemia induced by fat with and without ethanol.

1. Serum lipid and apolipoprotein levels, distribution and composition of high-density lipoprotein (HDL) subfractions and lecithin:cholesterol acryltransferase activity were analysed in nine normolipidaemic subjects, in whom a hypertriglyceridaemic state was induced by the acute administration of ethanol (40 g) plus fat (70 g) or of fat only. 2. Triglyceride (TG) levels increased by 180% 4-6 h after fat plus ethanol intake, the hypertriglyceridaemic response being inversely correlated with the basal HDL2 mass (r = -0.82). Serum apolipoprotein (apo) B levels rose by 8%, HDL-cholesterol decreased by 10% and HDL-TG increased by 57% at 6-8 h. 3. When ethanol was omitted, serum cholesterol and TG rose by 6% and 70%, respectively; both apo AI and apo B levels went up by 8%, whereas HDL-cholesterol rose progressively (15%) at 12 h. 4. The flotation rates of both HDL2 and HDL3 increased, reaching a maximum 6-8 h after ethanol plus fat intake. These changes were due to an increase in TG and phospholipid contents, whereas cholesteryl esters and proteins decreased. 5. The alterations in HDL are attributable to the increase in TG-rich lipoproteins, to the stimulated cholesterol esterification (+15%) and to an enhanced transfer of newly formed cholesteryl esters to apo-B-containing lipoproteins in exchange for TG. 6. Changes in HDL properties were evident only when ethanol was given concomitantly with fat. 7. These findings suggest that in the postprandial phase lipoprotein changes may occur, which facilitate an improved removal of cholesterol from tissues.

Adolescent↗
PubMedDate not supplied

Tolerability of fibric acids. Comparative data and biochemical bases.

Fibric acids are an established class of drugs for the treatment of hyperlipoproteinaemias. Although they have been in use for 30 years or longer, some doubts remain as to their relative tolerability, both as a class and as single agents. Some side effects, e.g. lithogenicity, may be related to their mode of action, while others, e.g. the acute muscular syndrome, may be linked to the spatial conformation of the molecule. These disadvantages should, however, be weighed against the additional, potentially therapeutic properties shown by these compounds. In particular, effects on maturity onset diabetes and hyperuricaemia, as well as a very interesting fibrinolytic potential, have been described for some of them. A painstaking comparative analysis of the major literature data pertaining to the clinical toxicological profile of these agents allow to conclude that, while belonging to a chemical class, fibric acids show dramatic differences from one another, in terms of side effects and of additional pharmacodynamic activities. Moreover, in the case of lithogenicity for example, considerable differences exist between normo- and hyperlipidaemic subjects. Overall, newer molecules of more sophisticated design have a significantly improved tolerability profile vs the old clofibrate.

Animals↗
PubMedDate not supplied

Apolipoprotein E epsilon 4 allele in Alzheimer's disease and vascular dementia.

The frequency of the epsilon 4 allele of the apolipoprotein E (apoE) is increased in familial and sporadic late-onset Alzheimer's disease, but its prevalence in non-Alzheimer dementias in Caucasian populations is unknown. We found that the frequency of the apoE epsilon 4 allele was 0.45 in 93 Alzheimer's disease patients, 0.46 in 23 vascular dementia patients, 0.31 in 13 dementia of the frontal type patients, and 0.18 in 51 elderly controls. The association of apoE epsilon 4 allele is not unique to Alzheimer's disease, and its importance as a risk factor for the disease should be reconsidered.

Adult↗
PubMedDate not supplied

Apolipoprotein A-IMilano. Correlation between high density lipoprotein subclass distribution and triglyceridemia.

Carriers of the apolipoprotein A-IMilano (apo A-IM) variant represent a selected group of subjects showing low levels of high density lipoprotein (HDL), variable hypertriglyceridemia, and low prevalence of atherosclerotic vascular disease. The distribution of HDL subfractions and the correlation with abnormalities in triglyceride transport were determined in these subjects. Sera from 24 apo A-IM carriers (A-IM+ and from age- and sex-matched normolipidemic controls (A-IM-) were analyzed by rate zonal ultracentrifugation. The A-IM+ subjects showed a marked decrease of HDL3 mass with reduced flotation rates and major compositional alterations; the HDL2 were nearly absent. The HDL subclasses from 10 A-IM+ subjects were resolved according to particle size by gradient gel electrophoresis (GGE). The HDL patterns detected in the carriers were unique in exhibiting a distinct peak in the (HDL3b)gge interval, undetectable in the controls. Three patterns reflecting the relative contributions of smaller (HDL3b)gge and larger (HDL3a)gge particles could be distinguished in the carriers, and these were clearly related to different triglyceride and HDL cholesterol levels in plasma. These findings in a highly selected group of subjects with generally low HDL levels and quite variable triglyceridemia confirmed the existence of relationships between alterations in triglyceride transport and abnormalities in the HDL subclass distribution, possibly reflecting the variable atherosclerotic risk in hypertriglyceridemic subjects.

Adult↗