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C Motta

Publications and source records attributed to C Motta.

At least 37 records · Page 2Linked to original sources

Oleic acid rich diet protects against the oxidative modification of high density lipoprotein.

Oxidative modifications of lipoproteins could contribute to the development of atherosclerosis, but the influence of dietary fats on high density lipoprotein (HDL) oxidative modification is unknown. This study was designed to determine whether a diet rich in oleic acid could modulate the oxidative modification of HDL3. Twenty two healthy men were randomly placed on a 32-wk crossover study of an oleic acid rich diet supplied by a variant of sunflower oil vs a linoleic acid rich diet provided by conventional sunflower oil. Plasma HDL3 obtained after the diet rich in oleic acid showed a significantly higher oleic acid content in the phospholipid than lipoprotein isolated after the linoleic acid rich diet. HDL3 isolated after the oleic acid rich diet had lower values of thiobarbituric acid reactive substances (TBARS) than HDL3 obtained after the linoleic acid rich diet both for native (mean +/- SE; 0.24 +/- 0.02 vs 0.42 +/- 0.08 nmol MDA/mg protein; p < 0.01) and copper oxidized HDL3 (0.75 +/- 0.06 vs 0.95 +/- 0.07 nmol MDA/mg protein; p < 0.01). Indeed, TBARS for native HDL3 were negatively correlated with the oleic acid to linoleic acid ratio and positively with the percentage of linoleic acid in their phospholipids. Interestingly, HDL3 after both diets had similar antioxidant vitamins A and E content. HDL3 overall composition and fluidity were similar after the two diets. Moreover, HDL3 obtained after both diets produced identical [3H] free cholesterol efflux from human monocyte-derived macrophages (29%) and fibroblasts (26%). In conclusion, HDL3 rich in oleic acid was less easily oxidized regardless of the content of antioxidants such as vitamins A and E. Therefore, dietary monounsaturated fatty acid prevent the oxidative modification of lipoproteins.

Cholesterol↗

Physicochemical changes in HDL3 after bezafibrate treatment: influence on free cholesterol efflux from human fibroblasts.

The effects of bezafibrate, a well-used fibric acid hypolipidemic agent, were investigated in 10 moderately hypertriglyceridemic patients. The aim was to quantify the physico-chemical modifications to high-density lipoprotein subfraction 3 (HDL3) induced by treatment and to assess, in vitro, the alterations in its principal physiological function, the efflux of intracellular free cholesterol. Treatment (200 mg/thrice/d for 3 months) resulted in a 48% decrease in plasma triglycerides, with an increase in the HDL cholesterol, due mainly to an increase in the HDL3 (P < 0.01). Composition analysis of HDL3 indicated an increase in cholesterol esters (P < 0.01), free cholesterol (P < 0.01), and phospholipids (P < 0.01), coupled with a decrease in the protein content of the molecule compared with pretreatment values. Fluorescence anisotropy at 24 degrees C was significantly higher post-treatment than pretreatment (P < 0.01). The cholesterol effluxing capacity of pretreatment HDL3 was 28%, and post-treatment this increased to 50% (P < 0.01). Multivariate analyses indicated that the increased capacity of HDL3 to promote free cholesterol efflux was, in part, due to increased HDL3 phospholipid content and a more adequate fluidity of the molecule. These findings suggest that bezafibrate induces a lowering of plasma triglycerides and that the resultant physico-chemical alterations of the HDL3 molecule make it more efficient as an acceptor of intracellular free cholesterol.

Adult↗

Differential effects of glycero- and sphingo-phospholipolysis on human high-density lipoprotein fluidity.

This study investigates the effect of enzymatic modifications of the HDL(3) surface lipid composition on their physical properties. Human HDL(3) (d: 1.125-1.21 g/ml) was treated either by an exogenous phospholipase A(2) from Crotalus adamanteus or by a sphingomyelinase from Staphylococcus aureus in the presence of albumin for various periods of time in order to obtain several degrees of hydrolysis. Glycerophospholipid hydrolysis ranged from 13 to 81% and sphingomyelinase action led to a 31-92% sphingophospholipid degradation. Physical properties of the surface of HDL(3) were examined by two spectroscopic methods: fluorescence polarisation and electron spin resonance. Glycerophospholipolysis treatment of HDL(3) enhanced the fluorescence anisotropy values (6-18%) and both relaxation correlation time (30-100%) and degree of order. All these results indicated a more rigid environment, a decreased mobility and an increased order of the surface lipids. Conversely, treatment of the HDL(3) with sphingophospholipase induced a progressive fluidization: fluorescence polarisation and degree of order decreasing down to 10% and relaxation correlation time down to 35% compared to native HDL(3). Taken together, all these observations suggest the relative importance of the two major phospholipids to modulate the fluidity and order of the surface of HDL(3) and could account for several recent physiological observations.

Electron Spin Resonance Spectroscopy↗

Alterations in erythrocyte membrane fluidity and fatty acid composition in glycogen storage disease.

Liver glycogen storage diseases (GSD) are disorders associated with severe dyslipidaemia which can induce cell membrane alterations. Reduced erythrocyte membrane fluidity has been associated with ischaemic cardiovascular disease. Our study has been designed to investigate membrane erythrocyte fluidity, and to determine its lipid composition and peroxidation parameters. Membrane erythrocyte fluidity has been studied by electron spin resonance (ESR) with two fatty acid nitroxide probes (5NS and 16NS). Twenty-five GSD cases aged 1-27 years and 15 controls aged 1-28 years were included. The erythrocyte membrane of GSD patients appeared less fluid with the two probes (P < 0.001). The membrane fatty acid pattern explained this reduced fluidity. Patients showed a relative saturated fatty acid (SFA) increase and polyunsaturated fatty acid (PUFA) decrease which induced lower PUFA/SFA ratio than in controls. We have provided evidence that the PUFA decrease was independent of the oxidative process. These findings should be taken into account for the management of the dietary treatment of GSD patients.

Adolescent↗

Lipid fluidity of triacylglycerol-rich lipoproteins isolated from copper-deficient rats.

Triacylglycerol-rich lipoproteins (TGRLP) were isolated from Cu-deficient and control rats. TGRLP from Cu-deficient rats appeared more fluid than those from controls as sensed by the fluorescence anisotropy of 1,6-diphenyl-1,3,5-hexatriene (DPH). This high fluidity was related to a low cholesterol:phospholipid ratio and high triacylglycerol content in these lipoproteins. TGRLP from Cu-deficient rats were more susceptible to in vitro peroxidation than lipoproteins from control rats as shown by the rate of diene conjugation. The damage induced by the peroxidation resulted in a more ordered state of the lipid fraction especially in lipoproteins from Cu-deficient rats. Thus, after in vitro peroxidation, TGRLP from Cu-deficient rats were more rigid than those from controls. These results suggest that Cu deficiency induces modifications in physicochemical properties of TGRLP which could affect their metabolism.

Animals↗

Changes in plasma membrane fluidity of Bryonia dioica internodes during thigmomorphogenesis.

Fluidity changes in plasma membrane (PM) lipid extracts or native membranes isolated from Bryonia dioica internodes after a mechanical stimulation were monitored by steady-state fluorescence polarization with 1,6-diphenyl-1,3,5-hexatriene as a probe. The signal was shown to rapidly induce an increase in the bulk lipid fluidity. This event was closely related to a relative enrichment in some phospholipid species (PC, PG and PS) as well as a significant increase in the unsaturation index of total fatty acyl chains. Free sterols and protein content did not appear to be involved into this process. After 48 h, lipids from rubbed internodes became less fluid than PM lipids from control internodes.

Cell Membrane↗

Physicochemical changes in human high-density lipoproteins (HDL) oxidized by gamma radiolysis-generated oxyradicals. Effect on their cholesterol effluxing capacity.

This paper describes an oxidative process of human high-density lipoproteins (HDL) based upon the action of oxygenated free radicals produced by water radiolysis (OH. and OH./O2.- free radicals at pH 7), monitored by both biochemical and physical markers. Classical biochemical markers (vitamin E, thiobarbituric acid-reactive substances (TBARS), conjugated dienes and differential fluorescence) were studied as a function of the radiation dose (from 0 to 800 Gy; dose rate = 2.7 x 10(-2) Gy.s(-1)). The fluorescence polarization anisotropy (r) was measured with 1,6-diphenylhexatriene (DPH). Vitamin E decrease and formation of lipid peroxidation products (thiobarbituric acid-reactive substances and conjugated dienes) were concomitant in the case of OH. free radicals alone, whereas these products appeared after a small threshold dose when OH. and O2.- free radicals were simultaneously produced in solution. At high radiation doses, TBARS concentrations have reached plateau values (approx. 2 or 7 nmol/mg lipid with OH. or OH./O2.- free radicals, respectively) which were much lower than those obtained after copper oxidation (approx. 15 or 29 nmol/mg lipid after 12 and 24 h incubation, respectively). The free radical-induced oxidative process has led to a rigidification of the HDL and was associated with low values of cholesterol effluxing capacities when these oxidized HDL were incubated with cholesterol-loaded human fibroblasts. Similar results were obtained with copper-oxidized HDL, under our experimental conditions. Consequently, these two kinds of oxidative modification of HDL resulted both in a loss of their capacity to remove cellular cholesterol, which could be explained by the fact that this ability was under the dependence of a HDL optimum fluidity.

Cholesterol↗

Dietary magnesium deficiency in rats enhances free radical production in skeletal muscle.

Recent studies suggest that free radicals may be involved in tissue injuries induced by magnesium deficiency. The aim of the present study was to assess the effect of magnesium deficiency on free radical production of skeletal muscle tissue. Male Wistar rats were pair-fed from weaning for 12 d either control or Mg-deficient diets containing 960 or 40 mg magnesium/kg diet, respectively. In the Mg-deficient rats, hypomagnesemia was accompanied by significantly lower magnesium and greater calcium concentrations in skeletal muscle tissue. Electron microscopy of skeletal muscle tissue revealed ultrastructural changes, including swelling mitochondria and disorganization of the sarcoplasmic reticulum network. Using the spin-trapping technique, we showed that significantly more hydroxyl radicals were generated in muscle homogenates of Mg-deficient rats. Moreover, the amount of spin trap adducts was increased in the presence of exogenous iron in both groups. In agreement with these observations, a greater concentration of thiobarbituric acid-reactive substances and a lower concentration of thiol groups were found in skeletal muscle of the Mg-deficient group compared with controls. These results strongly support the hypothesis that free radical-mediated injury could contribute to skeletal muscle lesions resulting from magnesium deficiency.

Animals↗

Anemia in copper-deficient rats: role of alterations in erythrocyte membrane fluidity and oxidative damage.

This study was designed to make precise the nature and the mechanism of the anemia induced by dietary copper (Cu) deficiency. Male Wistar rats were pair fed from weanling for 6 wk either a Cu-deficient or a control diet. The reduced red blood cell (RBC) 51Cr survival indicates an increased destruction of RBC during Cu deficiency. 1,6-Diphenyl-1,3,5-hexatriene fluorescence polarization studies revealed an increase in the fluidity of erythrocyte membranes from deficient rats. The reduced cholesterol-to-phospholipid ratio was consistent with the increased fluidity. Other results indicate an increased vulnerability of RBC to hemolysis in dilute hydrogen peroxide and an increased formation of lipid peroxidation products. Before exposure to free radical stress, electron spin resonance studies in intact RBC revealed decreased correlation time of 16-doxyl-stearic acid, confirming a more fluid membrane in RBC from Cu-deficient rats. After in vitro peroxidation, RBC from Cu-deficient rats showed a more ordered state of membrane lipids compared with controls. Together, these studies demonstrate the hemolytic nature of the anemia. The shortened survival of erythrocytes apparently results from changes in membrane fluidity and enhanced susceptibility to peroxidation.

Anemia↗

Membrane fluidity and adherence to extracellular matrix components are related to blast cell count in acute myeloid leukemia.

The level of blast cells in peripheral blood in acute myeloid leukemia (AML) varies in individual patients. The bone marrow egress of hematopoietic cells is an unclear phenomenon in which cell deformability and cytoadhesion to the extracellular matrix are involved. One component of deformability is the membrane fluidity. Using fluorescence polarization, we have studied the fluidity of blast cell membranes from 22 AML patients. This membrane was found to be highly fluid and a statistically significant correlation was found between the increase in membrane fluidity and the number of blast cells in the blood. Studying interaction between blast cells and several components of bone marrow stroma, we found adhesion to fibronectin and fibroblastic extracellular matrix. Adhesion to the extracellular matrix was inversally correlated to the level of blast cells in the blood. The observed increase in membrane fluidity and reduction of adhesion to bone marrow stroma may result in an increase of blast cells egress in AML.

Acute Disease↗

An interactive learning environment for health care professionals.

This article summarizes experiences to date with building and deploying a clinical simulator that medical students use as part of a 3rd year primary care rotation. The simulated microworld helps students and health care professionals gain experience with and learn meta-cognitive skills for the care of complex patient populations that require treatment in the biopsychosocial-value dimensions. We explain lessons learned and next steps resulting from use of the program by over 300 users to date.

Computer Simulation↗

Case report 771: Melorheostosis in association with desmoid tumor.

Melorheostosis is a rare congenital disease, some 300 cases have been reported in the literature. The main purpose of this case report is twofold: (1) to present an unusual case of melorheostosis of the right hand, beginning in infancy, with serial radiographic studies to show the gradual progression of the disease; and (2) to present the first case with the development of "aggressive" fibromatosis (desmoid tumor) of the adjacent soft tissues, associated with melorheostosis.

Child↗

Effect of ethanol on rat gastric surfactant: a fluorescence polarization study.

BACKGROUND: Gastric surfactant is believed to protect gastric mucosa by the hydrophobic properties of its phospholipidic component, which are reflected in the fluorescence polarization of a lipophylic fluorescent probe. The present study aimed to observe the consequences of intragastric administration of 40% ethanol on the physical properties of rat gastric surfactant. METHODS: Fluorescence polarization studies and lipid composition of gastric mucosal surface scrapings were performed. RESULTS: Time course experiments indicated that the ulcerogenic action of ethanol occurred along with a fluidization of the surface scrapings followed by secondary rigidification. The fluidizing effect of ethanol was related to modifications of the molecular dynamics of lipid structures. The rigidifying effect of ethanol was a result of an increase in the cholesterol-triglyceride and cholesterol-phospholipid ratios and an increase in the percent composition of phosphatidyl-ethanolamine of surface scrapings. CONCLUSIONS: The results suggest that alcohol could alter the gastric mucosal barrier by its disorganizing effect on the molecular dynamics of the gastric surfactant. The second rigidifying effect of ethanol could be a part of the damage repair phenomenon.

Animals↗

Fluidity state of lymphocyte plasma membrane in malignant hyperthermia susceptible pigs and humans.

Recent studies suggest that abnormalities occur at the lipid level in malignant hyperthermia susceptible humans and pigs. To test this hypothesis, we first investigated the physical state of plasma membranes of lymphocytes isolated from normal and malignant hyperthermia susceptible swine. In halothane-challenged pigs, malignant hyperthermia susceptibility was also assessed by ryanodine binding assay on purified sarcoplasmic reticulum membranes. The results clearly show that plasma membrane of lymphocytes from malignant hyperthermic pigs are significantly more fluid than controls. We then attempted to apply the same methodology to lymphocytes prepared from human patients previously diagnosed by the halothane and caffeine contracture test. In that case, there was no clear relationship between malignant hyperthermia susceptibility and the fluidity state of lymphocyte plasma membranes.

Animals↗

Fetal blood cell membrane fluidity in small for gestational age fetuses.

Blood cells membrane fluidity was assessed prenatally by fluorescence polarization for anisotropy, microviscosity, degree of order and fusion activation energy in 20 fetuses who underwent percutaneous umbilical blood sampling for intrauterine growth retardation (IUGR) and in 25 controls for normal weight sampled for other indications. Simultaneously, blood samples were collected from each mother for comparison. Regulators of membrane fluidity (i.e., cholesterol, phospholipids, free fatty acids) were also assessed. Student t test was employed for analysis. Membrane fluidity was lower in control fetal cells than in adults (p < 0.05) and lower in IUGR fetuses than in controls (p < 0.05). The mechanism may involve a low cholesterol concentration and a low unsaturated/saturated free fatty acids ratio in fetal blood cells membranes and plasma. Fetal cells membrane fluidity reflects in part fetal nutritional status.

Blood Cells↗

Dietary monounsaturated fatty acids enhance cholesterol efflux from human fibroblasts. Relation to fluidity, phospholipid fatty acid composition, overall composition, and size of HDL3.

This study was designed to determine whether modifications induced by dietary fats on the high-density lipoprotein3 (HDL3) physicochemical characteristics could affect cholesterol efflux and intracellular cholesterol content, leading to upregulation of low-density lipoprotein (LDL) receptor activity from cultured fibroblasts. Serum HDL3S were obtained from 12 healthy women aged 26 to 49 years who adhered to four 7-week isocaloric diets containing 30% of the caloric intake as fat. Of the total calories, 15.6% of each diet was provided by (1) milk fats, rich in saturated fatty acids; (2) sunflower oil, rich in n-6 polyunsaturated fatty acids; (3) olive oil, rich in monounsaturated fatty acids; and (4) rapeseed oil, rich in n-3 polyunsaturated fatty acids. HDL3 isolated after the monounsaturated fatty acid diet induced the greatest cellular [3H]free cholesterol efflux, reduced the content of intracellular cholesterol, and enhanced 125I-LDL degradation. Univariate regression analyses suggested that the increased capacity of HDL3 to promote cellular [3H]free cholesterol efflux was in part due to its greater fluidity, higher cholesteryl ester content, elevated linoleic to linolenic acid ratio in phospholipids, and its smaller size. In conclusion dietary fats induced physicochemical changes in HDL3, which strongly modulated cellular cholesterol homeostasis in vitro. These data also suggest a novel mechanism by which dietary fats exert their effect on atherosclerosis.

Adult↗