Search PubMed⌕ Search

Biomedical subjects

L Masana

Publications and source records attributed to L Masana.

At least 55 records · Page 3Linked to original sources

Effect of dexfenfluramine on energy expenditure in obese patients on a very-low-calorie-diet.

AIM: To investigate the effect of dexfenfluramine (dF) on Energy Expenditure (EE). DESIGN: 20 obese females were studied in a double-blind design. Pre-diet and at 14 and 28 days of VLCD and dF treatment (30 mg/d) or placebo, Resting Metabolic Rate (RMR), 3 h-Thermic Effect of Food (3 h-TEF) and body composition were determined. EE and body composition were measured by indirect calorimetry and bioelectrical impedance, respectively. RESULTS: No differences between groups were observed in relation to weight loss, body composition changes or RMR. At 3 h postprandial, the EE was still elevated in both groups. No changes on TEF were observed in the placebo group during VLCD. In contrast, TEF decreased in dF group during VLCD (P < 0.05). No significant differences in TEF at the end of the study were observed between groups. CONCLUSION: These results suggest that dF modifies 3 h-TEF but not RMR in obese patients during VLCD administration.

Adult↗

In vitro oxidised HDL is recognized by the scavenger receptor of macrophages: implications for its protective role in vivo.

To assess the effects of oxidative modification, human HDL was oxidised in vitro for 12 h (Ox-HDL12) and 24 h (Ox-HDL24) under similar conditions to those commonly used for LDL. The procedure resulted in: an increase in thiobarbituric acid reactive substances but with marginal change in electronegativity; protein denaturation accounting for 16% and 45% loss of immunoreactive apoprotein A-I in the Ox-HDL12 and Ox-HDL24 respectively relative to the non-oxidised, native HDL (Nat-HDL); a decrease in the polyunsaturated fatty acids of the triglyceride, cholesterol ester and phospholipid components of the lipoprotein; an increase in the proportion of short chain saturated fatty acids while the monounsaturated fatty acids remained relatively unchanged. Studies with human macrophages demonstrated: a decrease of 16% and 30% in the capacity of the Ox-HDL12 and Ox-HDL24 respectively to efflux intracellular free cholesterol; 125I-Ox-HDL24 uptake and degradation was directly comparable with that of 125I-Ac-LDL; the addition of excess unlabelled Ox-HDL24, Ac-LDL, Ox-LDL24 and Nat-HDL resulted in 74%, 67%, 69% and 19% displacement of the 125I-Ox-HDL24 respectively; fucoidin and dextran sulphate displaced 125I-Ox-HDL by 20% and 40% respectively; intracellular free and esterified cholesterol was increased 2.5-fold and 4-fold respectively relative to Nat-HDL on incubation with Ox-HDL24. These findings suggest that HDL is susceptible to oxidative modification leading to recognition by the scavenger receptor of macrophages and subsequent intracellular cholesterol accumulation. As such, the in vivo protective role of HDL in cardiovascular disease can be reversed in those circumstances in which HDL, like LDL, undergoes oxidative modification.

Cells, Cultured↗

Plasma lipoprotein alterations in patients with chronic hepatocellular liver disease resulting from alcohol abuse: effects of alcohol intake cessation.

Cholesterol and triglyceride in plasma and lipoprotein fractions and serum apoprotein concentrations were measured in 51 chronic alcoholic subjects; 23 had minimal or mild hepatic changes (steatosis and/or fibrosis) and 28 had cirrhosis. Of the latter, 16 had stopped alcohol consumption at least 3 months before the study, while the other 12 and all the mildly affected patients had continued drinking. None of the patients presented with cholestasis or alcoholic hepatitis. The control group was composed of 15 healthy, non-drinking volunteers selected from the hospital staff with an age- and sex-distribution similar to that of the alcoholic group. Patients with minimal hepatic changes had plasma total cholesterol concentrations within the ranges of the normal population but with increased high density lipoprotein and decreased low density lipoprotein fractions. Total plasma triglyceride values were not significantly elevated but the distributions in the low density lipoprotein and high density lipoprotein fractions were significantly increased in patients compared to controls. This alteration was accompanied by a consistent increase in serum apolipoprotein C-III concentration. Conversely, in patients with cirrhosis, serum concentrations of apolipoproteins A-I and B were significantly lower and were reflected in the cholesterol concentrations in the lipoprotein fractions. Comparisons between abstainers and non-abstainers within the group with cirrhosis indicated that cessation of alcohol intake was not sufficient to rectify lipoprotein dysfunction following damage from cirrhosis.

Adult↗

Limitations of the Friedewald formula for estimating low-density lipoprotein cholesterol in alcoholics with liver disease.

The accuracy of the Friedewald formula in estimating low-density lipoprotein (LDL) cholesterol was investigated in 47 alcoholic patients with liver disease (21 minimal-change, 26 cirrhotic) by comparing the results with those obtained by sequential preparative ultracentrifugation. In 14% of subjects with minimal-change disease, the error in the estimated LDL cholesterol was 50% +/- 9% (mean +/- SD; range 40-59%) and was related to the degree of attendant hypertriglyceridemia (r = 0.98; P < 0.001). A similar degree of error was observed in patients with cirrhosis, despite the absence of hypertriglyceridemia; an abnormal VLDL cholesterol: triglyceride ratio was the contributory factor in the discrepancy. We conclude that, as is the case in other clinical pathologies in which abnormalities of lipoprotein composition have been described (e.g., diabetes), the Friedewald formula to estimate LDL cholesterol may be inappropriate in chronic alcoholics, particularly those in whom a degree of hepatic dysfunction may be suspected.

Adult↗

[The relationship between biliary lithiasis and lipoproteins isolated by ultracentrifugation].

BACKGROUND: The prevalence of biliary lithiasis was studied in a sample of rural female population by calculation of the risk factors associated and the correlation between biliary lithiasis and serum lipoprotein concentrations. METHODS: Two hundred forty-nine women between the ages of 20-75 years in whom complete anamnesis and calculation of the Quetelet index (QI) were performed, were the subjects of this study. The investigation of biliary lithiasis was carried out by echography. Serum lipoprotein concentrations were determined by sequential ultracentrifugation. RESULTS: The prevalence of biliary lithiasis in the population studied was of 10.4%. A tendency to increase by age was observed and a peak between 50-60 years of age (p < 0.05) was registered. Biliary lithiasis was more frequent among the obese population (p < 0.05). With respect to lipoprotein parameters, all the lipid values of the different fractions demonstrated to be higher in the lithiasic population, although only the differences in cholesterol vehicled by very low density lipoproteins (C-VLDL) achieved statistical significance) (p < 0.001). CONCLUSIONS: The prevalence of biliary lithiasis in the female population studied is similar to that reported in other Western populations, and an increasing tendency in the prevalence of biliary lithiasis with age and obesity was observed. The levels of C-VLDL are higher in women with biliary lithiasis than in those without.

Adult↗

[Polymorphism (RFLP-PstI) of the apoprotein A-I gene in a healthy population. Its relation to high-density lipoproteins].

BACKGROUND: Some RFLPs for the genes encoding for apoproteins have been associated with dyslipidemia and the predisposition to atherosclerosis. It is of interest to investigate the apo A-I gene in a Mediterranean population, since it is the major protein in HDL. METHODS: We studied the A-I C-III A-IV gene cluster RFLP defined by the endonuclease Pst I in 149 healthy males randomly selected among industrial workers in Tarragona. The mean age was 40 +/- 7 years (range 20 to 62). We analysed cholesterol and triglycerides in plasma and the lipoprotein fractions (VLDL, IDL, LDL and HDL) obtained by ultracentrifugation. The RFLP was determined for the enzyme Pst I in the A-I C-III A-IV gene cluster by the Southern blotting method. RESULTS: The genotype distribution was P1P1 81.9%, P1P2 14.8% and P2P2 3.4% and the allelic frequency was P1 89.3% and P2 10.7%. The plasma cholesterol, triglycerides, apo A-I and apo B did not show significant differences between these groups. The P2P2 subjects had lower HDL-C values (P1P1 1.17 +/- 0.39 mmol/l, P1P2 1.16 +/- 0.28 mmol/l y P2P2 0.89 +/- 0.14 mmol/l; p < 0.01). CONCLUSIONS: The distribution of the genotypes in the Mediterranean population were similar to that observed in the USA and in Europe. P2P2 subjects had decreased HDL cholesterol but the low prevalence of the genotype being very low limits its value as a marker of coronary artery disease risk.

Adult↗

Low-density lipoprotein metabolism in rats treated with cyclosporine.

Metabolic mechanisms underlying the observations of elevated cholesterol concentration of low-density lipoprotein (LDL) in organ-transplanted patients on long-term immunosuppressant cyclosporine therapy were explored using cyclosporine-treated rats as an experimental model. As in patients, treatment with cyclosporine induced a significant elevation of plasma cholesterol level, mainly in LDL cholesterol, with a decrease in high-density lipoprotein (HDL) cholesterol level. In an in vivo cross-over study design, differentially radioiodinated homologous LDL from donor cyclosporine-treated rats (Cyc-LDL) and excipient-only-treated control rats (Exc-LDL) were injected into recipient cyclosporine-treated rats (Cyc-rats), excipient-only--treated control rats (Exc-rats), and untreated rats (Unt-rats). From the isotope disappearance curves, the fractional catabolic rate (FCR) and production rate were calculated. The results showed that FCR and production rate were significantly reduced in Cyc-rats compared with control Exc-rats and Unt-rats. The decrease was independent of the donor LDL source. In vitro LDL ligand-receptor assays indicated a twofold higher degradation of Cyc-LDL by cultured rat fibroblasts, and hence could not account for the decreased clearance observed in vivo. These results suggest that the elevated concentrations of LDL cholesterol associated with cyclosporine treatment result not from a cyclosporine-induced modification of the LDL molecule, which could diminish its receptor-mediated clearance/catabolism, but possibly from an in vivo pharmacological property of cyclosporine such as an induced hepatic dysfunction.

Analysis of Variance↗

[A toxic syndrome and subcutaneous nodules as the only clinical manifestation of systemic sarcoidosis].

Sarcoidosis is a systemic disease with frequent cutaneous manifestations. Among these exists a predominance of the so-called unspecific lesions because of their histopathological features. Within the specific lesions, that is those which showed non-caseous granulomas, subcutaneous nodules are underlined, which have been associated with chronic sarcoidosis with a frequency of 1.4%-6%. These lesions appear during the evolution of the disease but rarely constitute an initial manifestation of it. The patient whose case is discussed had a debut with toxic syndrome and subcutaneous nodules. Histopathological study of these nodules showed the existence of non caseous granulomas formed by histiocytes, epithelioid cells, Langhans and foreign body giant cells. Lobulet hepatic granulomas were showed together with mediastinal pulmonary captation of gallium. We conclude that sarcoidosis must be considered when performing the differential diagnosis of the disease which debut with subcutaneous nodules.

Biopsy↗

Interaction of oxidized low density lipoproteins with both apo B,E and scavenger receptors. A model for its production in vitro.

Oxidation of low density lipoprotein (LDL) has been demonstrated in vivo and directly implicated in the process of foam cell formation. Consequently, a considerable research effort has been devoted to the assessment of the metabolic behaviour of oxidized LDL. We have developed a simple and reproducible model to obtain oxidized LDL consisting of the dialysis of LDL (4 g/l) contained in a cellulose bag against 5 litres of 0.15 M NaCl, 5 microM CuSO4, 0.6 mM FeCl3, pH 7.4, 37 degrees C with constant oxygen bubbling. While the resulting particles have a number of physicochemical properties suggesting lipid oxidation, neither apo B fragmentation nor modification in the size and shape were observed. This oxidized LDL showed internalization into cells through both the apo B,E and the scavenger receptors and the rate of removal from the plasma in injected rats was faster than that observed for normal LDL. We suggest that these particles may represent an equivalent to the circulating oxidized LDL postulated in humans.

Chemical Phenomena↗

Low density lipoprotein ligand-receptor interactions in normal healthy individuals characterized by their XbaI apolipoprotein B DNA polymorphism.

A DNA restriction fragment length polymorphism (RFLP), observed with the XbaI restriction enzyme digestion of peripheral lymphocyte genomic DNA and a 3.5 kb probe 3' end of the apolipoprotein B gene, was investigated in 228 normal healthy males. Lipoprotein measurements were conducted on fasting plasma and related to the genotype; the X2X2 homozygotes (the X2 allele contains the enzyme cutting site) had significantly higher plasma cholesterol, low density (LDL) cholesterol and LDL apolipoprotein B. Thirty subjects (10 from each of the X1X1, X1X2 and X2X2 groups) were recalled and the LDL receptor activity measurements, conducted on peripheral venous blood lymphocytes, indicated no significant differences between the genotypes. However, when LDLs isolated from these individuals were assayed for ligand-receptor interaction with a human embryonic lung fibroblast cell line, significantly different maximum binding (Bmax) values in the X2 allele-bearing individuals were observed. This paradoxically elevated in vitro binding and degradation of LDL from X2X2 subjects suggests that the elevated concentrations of LDL cholesterol observed with this genotype in vivo does not result from a defective ligand-receptor interaction directly related to this polymorphism.

Adult↗

Relationship between hepatic lipid peroxidation and fibrogenesis in carbon tetrachloride-treated rats: effect of zinc administration.

1. Lipid peroxidation and hepatic fibrogenesis were investigated in 25 carbon tetrachloride-treated rats and in 25 control animals. Rats were further divided into two groups to receive either a standard diet or one supplemented with zinc. From each group, animals were killed at weeks 3 and 18 of the experiment for histological and biochemical assessments which included hepatic lipid peroxide and collagen concentrations and plasma zinc concentration as well as the hepatic activities of proline hydroxylase and collagenase. 2. Results indicated that oral zinc supplementation was associated with a decrease in lipid peroxidation (mean 51%; P < 0.05), collagen deposition (mean 32%; P < 0.001) and proline hydroxylase activity (mean 30%; P < 0.05) at week 18, together with an increase in collagenase activity (mean 208%; P < 0.01) at week 3, in carbon tetrachloride-treated rats. 3. There was a significant direct correlation between lipid peroxidation and proline hydroxylase activity in carbon tetrachloride-treated rats (r = 0.52; P < 0.01) and also a significant inverse correlation between lipid peroxidation and plasma zinc concentration in these animals (r = -0.62; P < 0.001). 4. These findings are consistent with the hypothesis that hepatic lipid peroxidation plays an important role in the aetiology of hepatic fibrogenesis and that zinc mitigates the process.

Animals↗