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Biomedical subjects

D Zambón

Publications and source records attributed to D Zambón.

11 recordsLinked to original sources
PubMed1999

Randomized crossover study of gemfibrozil versus lovastatin in familial combined hyperlipidemia: additive effects of combination treatment on lipid regulation.

The most appropriate therapy for combined hyperlipidemia remains to be determined. We compared the lipid-regulating effects of gemfibrozil and lovastatin in 30 patients with familial combined hyperlipidemia (FCHL) in a randomized, double-blind, placebo-controlled crossover study including 8-week courses of one drug followed by a washout period and a crossover phase to the alternate drug. After completion of the trial, open-label combination therapy was given for up to 12 months. Lovastatin was more efficacious than gemfibrozil in the reduction of total cholesterol (23% v. 9%, P<.001) and low-density lipoprotein (LDL) cholesterol (28% v. 2%, P<.001), whereas gemfibrozil surpassed lovastatin in the reduction of triglycerides (48% v. 0%, P<.001) and very-low-density lipoprotein (VLDL) cholesterol (50% v. 19%, P = .005) and the increase of high-density lipoprotein (HDL) cholesterol (18% v. 4%, P = .005). Lovastatin caused a greater decline in total apolipoprotein B (apo B) and LDL apo B than gemfibrozil, whereas VLDL apo B decreased only after gemfibrozil therapy. Drug-induced changes in lipoprotein composition indicated that gemfibrozil reduced both the number and size of VLDL particles and lovastatin decreased the number of LDL particles. Combined treatment was safe and had additive effects on lipids, causing significant (P<.001) reductions in total cholesterol (32%), triglycerides (51%), LDL cholesterol (34%), and apo B (26%) and an increase in HDL cholesterol (19%). Target LDL cholesterol levels were achieved only in 11% of patients given gemfibrozil alone and triglycerides decreased to target levels in 22% after lovastatin alone, whereas combined therapy normalized both lipid fractions in 96% of patients. Thus, in FCHL, gemfibrozil has no effect on LDL cholesterol levels but favorably influences the putative atherogenic alterations of lipoprotein composition that are related to hypertriglyceridemia. Conversely, lovastatin markedly decreases LDL cholesterol but has little effect on triglyceride-rich lipoproteins. Combination treatment safely corrects all of the lipid abnormalities in most patients.

Adult↗
PubMed1998

Lack of interaction of apolipoprotein E phenotype with the lipoprotein response to lovastatin or gemfibrozil in patients with primary hypercholesterolemia.

The magnitude of serum lipid changes in response to hypolipidemic drugs varies considerably between individuals. These differences may be due to interactions between genetic and environmental factors that effect drug bioavailability or the capacity of the lipid-regulating enzyme and receptor targets to be affected. The apolipoprotein E (apoE) gene locus has been examined in this regard, but reports are conflicting on the effect of its variability on the response to hypolipidemic drugs. We investigated the effect of apoE polymorphism on the serum lipid response to the hepatic hydroxymethyl glutaryl coenzyme A (HMG CoA) reductase inhibitor lovastatin and the fibric acid derivative gemfibrozil. Lipoprotein changes were assessed after 12 weeks of therapy in 106 patients with primary hypercholesterolemia and combined hyperlipidemia treated with lovastastin and in 63 given gemfibrozil therapy. No significant effect of the apoE phenotypes E3/2, E3/3, or E4/3 on the heterogeneity of lipid responses to either drug was found.

Adult↗
PubMed1998

Lipoprotein composition and oxidative modification during therapy with gemfibrozil and lovastatin in patients with combined hyperlipidaemia.

AIM: To evaluate the resistance to oxidation of human lipoproteins after hypolipidaemic therapy. METHODS: VLDL and LDL samples were obtained from patients with Familial Combined Hyperlipidaemia included in a randomized, double-blind, cross-over study, with 8 weeks of active treatment (gemfibrozil, 600 mg twice daily, or lovastatin, 40 mg daily) and a 4-week wash-out period. Oxidation related analytes after Cu-induced oxidation of VLDL and LDL have been investigated. Further, in order to relate possible changes in oxidative behaviour to lipoprotein composition, the proportion of the lipid species transported by lipoproteins (triglycerides, phospholipids, and cholesteryl esters), the molar composition of fatty acids for each lipoprotein lipid, and the content of antioxidant vitamins in plasma (vitamin C) and lipoproteins (vitamin E) have been studied. RESULTS: Both drugs reduced the plasma concentration of apo-B lipoproteins (-23% gemfibrozil, -26% lovastatin), but whereas lovastatin affected mainly LDL-cholesterol (-30%), gemfibrozil reduced triglycerides (-49%) and VLDL-cholesterol (-48%). Lovastatin treatment had no effect on the lipid and protein composition, the fatty acid profile, or the vitamin E content of either VLDL or LDL; likewise, lipoprotein oxidation markers (Cu-induced conjugated dienes, thiobarbituric acid reactive substances formation, and lysine residues) were similar before and after lovastatin treatment. Gemfibrozil therapy also had no effect on lipoprotein oxidation; nevertheless, it consistently: a) decreased the proportion of LDL-triglycerides (-32%), and b) increased the proportion (molar%) of 18:3 n-6 in VLDL triglycerides (+140%), phospholipids (+363%) and cholesteryl esters (+53%). CONCLUSIONS: Based on these results, lovastatin and gemfibrozil do not adversely affect lipoprotein oxidation in patients with mixed dyslipidaemia. In the case of gemfibrozil, this occurs in spite of an increased proportion of some polyunsaturated fatty acids in VLDL. In the context of a fixed dietary intake, such modifications suggest that the drug influences liver enzyme activities involved in fatty acid chain synthesis (elongases and desaturases).

Double-Blind Method↗
PubMed1996

Apolipoprotein E polymorphism and gallstones.

BACKGROUND & AIMS: Apolipoprotein (apo) E is a genetically polymorphic protein influencing lipoprotein metabolism and the risk of both atherosclerosis and Alzheimer's disease. As opposed to common apo E3, apo E2 decreases and apo E4 increases hepatic lipoprotein uptake; hence, apo E4 could promote gallstone formation by increasing hepatic and biliary cholesterol concentrations. This study was designed to evaluate whether apo E polymorphism is related to gallstone risk. METHODS: apo E phenotype was determined in subjects older than 40 years of age (160 with and 125 without gallstones) and in 61 patients with cholesterol gallstones who underwent cholecystectomy. Bile composition, nucleation time, and gallstone features were analyzed in surgical patients. RESULTS: The E4/3 phenotype was enriched in both patients with gallstones and those who underwent cholecystectomy, with significantly (P < 0.006) higher epsilon 4 allele frequencies than in gallstone-free subjects (odds ratio, 2.67 [95% confidence limits, 1.23-5.93] and 3.62 [95% confidence limits, 1.49-8.91], respectively); women, but not men, accounted for these differences. The prevalence of the epsilon 4 allele increased with age in patients with gallstones, whereas the opposite occurred in gallstone-free subjects. Biliary lipid and gallstone cholesterol content tended to increase in the sequence E4 > E3 > E2 in patients who underwent cholecystectomy. CONCLUSIONS: Carrying the apo E4 isoform is a genetic risk factor for cholelithiasis in humans, thus adding another adverse effect of apo E polymorphism on health.

Adult↗
PubMed1995

[Carotid atherosclerosis evaluated by two-dimensional ultrasonography in patients with primary hypercholesterolemia].

BACKGROUND: Two-dimension ultrasonography permits to noninvasively quantify extracoronary atherosclerosis. The objective of this study was to assess preclinical atherosclerosis of the extracranial carotid arteries in patients with primary hypercholesterolemia. METHODS: Lipid and nonlipid cardiovascular risk factors were evaluated in 206 patients with dyslipidemia (127 men and 79 women, mean age 49 years, range 18-75), and a multifactorial cardiovascular risk profile was constructed for each patient. Ultrasound measurements of the intima-media thickness in the common carotid artery of each side were taken, and the number and height of any atheroma plaques present were quantified. RESULTS: Asymptomatic plaques were found in 120 patients (58%), and were more frequent in men than in women (65 vs 47%, p = 0.009), and in patients with than in those without prior coronary heart disease (80 vs 50%, p < 0.001). Both intimal thickening, indicative of early atherosclerosis, and the extent of arterial wall involvement with plaques, which represents an advanced stage of the disease, increased significantly with age and with increasing multifactorial cardiovascular risk, reflecting a positive relation between signs of atherosclerosis and the burden of risk factors. Intima-media thickness also increased with increasing plaque score, indicating the generalization of atherosclerosis. CONCLUSIONS: The high prevalence of preclinical carotid atherosclerosis confirms the atherogenic risk of primary dyslipidemias. The relation between carotid lesions and both coronary heart disease and multifactorial risk supports the validity of arterial ultrasound studies for cardiovascular risk prediction.

Adolescent↗
PubMed1995

Effect of apolipoprotein E polymorphism on the serum lipid response to a hypolipidemic diet rich in monounsaturated fatty acids in patients with hypercholesterolemia and combined hyperlipidemia.

We investigated the effect of variation at the apolipoprotein (apo) E gene locus on the serum lipid response to a hypolipidemic diet rich in monounsaturated fatty acids (MUFA). Lipoprotein changes were assessed in 122 outpatients with type IIa (n = 70) and type IIb (n = 52) hyperlipidemia [80 men and 42 women with apo E phenotypes 3/2 (n = 27), 3/3 (n = 48), and 4/3 (n = 47)] who were switched from their basal diet containing 40% fat (22% MUFA) to an isoenergetic diet containing 31% fat (MUFA content similar to that of the basal diet) for 12 wk. Significant (P < 0.005) reductions of total, LDL, and VLDL cholesterol; triglycerides; and apo B occurred in subjects regardless of WHO phenotype. Triglycerides and VLDL cholesterol decreased more in type IIb than in type IIa subjects: 25% vs 12% and 21% vs 15%, respectively (P = 0.01). HDL cholesterol tended to decrease only in women. The heterogeneity of lipoprotein responses to dietary intervention was unrelated to apo E phenotypes. In these hyperlipidemic subjects, however, diet-induced favorable changes in serum lipoproteins were selectively influenced by WHO phenotype.

Adult↗
PubMed1994

In-vitro effect of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors on non-hepatic LDL receptor activity: evidence of lack of stimulatory effect of pravastatin.

BACKGROUND: It is speculated that, as a result of its tissue selectivity, pravastatin may be a safer drug than the lipophilic 3-hydroxy-3-methylglutaryl Coenzyme A (HMG-CoA) reductase inhibitors in combination therapy involving drugs with potential muscle toxicity. Several studies have shown specific inhibitory activity on hepatic cholesterogenesis and a potent induction of hepatic low-density lipoprotein (LDL) receptors. However, data about its effect on stimulation of LDL receptor activity on non-hepatic cells are not available. METHODS: Several experiments were carried out in order to assess the in-vitro effect of HMG-CoA reductase inhibitors on the activity of LDL receptors of human non-hepatic cells. Lymphocytes from both normolipidemic controls and patients with heterozygous familial hypercholesterolemia along with human fibroblasts were cultured in both the presence and absence of pravastatin and lovastatin. RESULTS: Pravastatin, at concentrations of 0.25-50 mumol/l, did not enhance the LDL receptor activity of lymphocytes derived from both patients with familial hypercholesterolemia and normolipidemic controls. In contrast, lovastatin, at concentrations of 0.25 mumol/l, increased the LDL receptor activity in both control lymphocytes and lymphocytes from patients with familial hypercholesterolemia by 121% and 148%, respectively. Fibroblast LDL receptor activity was not altered by pravastatin at a concentration of 50 mumol/l, whereas lovastatin at the same concentration increased the LDL uptake by 153%. CONCLUSION: From in-vitro experiments of LDL receptor activity stimulation, we conclude that pravastatin has little effect on non-hepatic cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Female↗
PubMed1991

Comparative study of a microporous cholestyramine analogue (filicol) and gemfibrozil for treatment of severe primary hypercholesterolemia. Short- and long-term results.

The hypolipidemic effect of gemfibrozil in severe hypercholesterolemia is not well established. Fifty patients with primary hypercholesterolemia (including 18 patients with familial hypercholesterolemia) and stable low-density lipoprotein cholesterol levels greater than 3.90 mmol/L (greater than 150 mg/dL) (6.10 +/- 1.30 [SD] mmol/L; 236 +/- 50 mg/dL) while on a hypolipidemic diet were assigned to treatment for 12 weeks with either 9 g/d of filicol, a microporous cholestyramine analogue, or 1.2 g/d of gemfibrozil in a randomized clinical trial. Tolerance was good with both drugs. Filicol and gemfibrozil caused similar decrements of total cholesterol (14% for both), low-density lipoprotein cholesterol (20% and 18%, respectively), and apolipoprotein B (16% and 21%, respectively). Close to 40% of the patients had decreases of greater than 25% in low-density lipoprotein cholesterol levels with both drugs. Gemfibrozil, but not filicol, significantly increased plasma high-density lipoprotein cholesterol (16%) and apolipoprotein A-I (17%) levels and reduced triglyceride levels (35%). No loss of efficacy was observed with either drug in subsets of patients who had a good 12-week response rate and had extended therapy for up to 12 months. This study demonstrates that gemfibrozil may have a beneficial effect on all aspects of the plasma lipid profile in patients with severe hypercholesterolemia, a clinical situation where it can be used with potential advantages over standard doses of anion-exchange resins.

Adult↗
PubMed1989

[Excessive intake of fats and cholesterol in hypercholesterolemic individuals. Effects of dietary intervention on plasma lipids and lipoprotein cholesterol].

Preliminary evidences suggest that both the frequency of ischemic heart disease and the plasma cholesterol levels are increasing in the Spanish population, whose dietary habits are becoming progressively "westernized". In the present work we used the food frequency method to evaluate the dietary habits of 30 hypercholesterolemic subjects. These and another 65 free-living individuals of both sexes, ages 18-77 yrs, with plasma cholesterol 301 +/- 41 mg/dl or 7.80 +/- 1.06 mmol/l (means +/- SD) were submitted to a hypolipidemic diet similar to the mediterranean diet in order to assess effects on plasma lipids and lipoprotein cholesterol. The usual diet contained (% kcal/day): total fat 37, saturated fat (S) 12, monoinsaturated fat 16 and poliinsaturated fat (P) 6, with P/S = 0.5 and a daily cholesterol intake of 506 mg. During dietary intervention, respective changes were: -7%, -5%, -1%, +2%, +0.6, and -304 mg. After a 3 - month dietary period, significant (p less than 0.001) decreases occurred in total plasma cholesterol (-40 mg/dl or -1.04 mmol/l, -14%), LDL-cholesterol (-35 mg/dl or -0.91 mmol/l, -16%) and triglycerides (-5 mg/dl or -0.28 mmol/l, -14%), while HDL-cholesterol and body weight did not change. Similar effects were obtained when diet was continued for 1 yr in a subgroup of 40 individuals. The responses of plasma cholesterol to dietary change had a normal distribution, with 17% hyporresponses and 15% hyperresponses. A marked decrease (-36%) of plasma triglycerides was observed in 12 subjects with IIb hyperlipidemia. The total cholesterol/HDL-cholesterol and LDL-cholesterol/HDL-cholesterol ratios improved in both men and women.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1985

Chronic hepatitis: a possible etiology of fatty liver.

In a survey of the etiology of hepatic steatosis, none of the known causes of fatty liver was identified in 12 of 137 patients with severe fatty changes (more than 50% of hepatic cells containing fat vacuoles) diagnosed over a 4-year period. The retrospective analysis of the clinical records of these patients disclosed the absence of symptoms, liver biopsy being performed because of persistent hypertransaminasemia, which had been discovered fortuitously in 10 cases and after acute hepatitis in two. None had HBsAg in serum. In addition to fatty changes, lobular necrosis was found in 11 cases and chronic inflammation of portal tracts in eight. Patients remained asymptomatic and had raised transaminases during a follow-up ranging from 1 to 3 years. The clinical, biochemical and follow-up features of these patients closely resemble those of patients with chronic hepatitis in Mediterranean countries. Thus it can be suggested that in some cases fatty liver may be a prominent feature of chronic hepatitis.

Adolescent↗