Alain Gerbi - Academia.edu (original) (raw)

Papers by Alain Gerbi

Research paper thumbnail of A 12-week randomized double-blind parallel pilot trial of Sinetrol XPur on body weight, abdominal fat, waist circumference, and muscle metabolism in overweight men

International Journal of Food Sciences and Nutrition, 2015

Overweight and obesity are associated to increased risk of developing non-communicable diseases t... more Overweight and obesity are associated to increased risk of developing non-communicable diseases that might dramatically affect life expectancy according World Health Organization. Overweight, obesity, and decline in physical activity are correlated to a significant propensity to lose skeletal muscle mass as a result of prolonged inflammation and oxidative stress whereas cohort surveys and clinical investigations have demonstrated health benefits of Citrus-based polyphenols to reverse such regression. Overweight men were included in a double-blind, randomized, parallel pilot trial where they received daily for a 12-week period 900 mg of a Citrus-based polyphenol extract, Sinetrol® XPur. Body composition, anthropometric, and blood parameters were assessed before and at the end of the intervention period. After 12 weeks, while the silhouette slimmed down, metabolic parameters were significantly improved and skeletal muscle catabolism held back. These data suggest that over a 12-week period, the efficacy of the supplement improve both overweight process and correlated skeletal muscle mass metabolism.

Research paper thumbnail of Regular consumption of Fiit-ns, a polyphenol extract from fruit and vegetables frequently consumed within the Mediterranean diet, improves metabolic ageing of obese volunteers: a randomized, double-blind, parallel trial

International journal of food sciences and nutrition, 2015

Epidemiological studies suggest that metabolic ageing process of overweight and obese populations... more Epidemiological studies suggest that metabolic ageing process of overweight and obese populations is associated with an increased risk of developing non-communicable diseases (NCDs). Inflammation, hyper-glycaemia, dyslipidemia and oxidative stress have been associated with early stages of NCDs development whereas cohort surveys have demonstrated health benefits of dietary polyphenols from various dietary sources to reverse such progress. Obese volunteers were included in a double-blind, randomized, parallel pilot trial where they received daily for a 12-week period 900 mg of a polyphenol-rich treatment extracted from fruit and vegetables frequently consumed within the Mediterranean diet. Anthropometric and blood parameters were assessed before and at the end of the intervention period. After 12 weeks, while the silhouette slimmed down, metabolic parameters were significantly improved and general satisfaction considerably ameliorated. These data suggest that over a 12-week period, th...

Research paper thumbnail of Lipolytic effect of a polyphenolic citrus dry extract of red orange, grapefruit, orange (SINETROL) in human body fat adipocytes. Mechanism of action by inhibition of cAMP-phosphodiesterase (PDE)

Phytomedicine : international journal of phytotherapy and phytopharmacology, 2008

The present study investigated the lipolytic (break of fat stored) effect of a citrus-based polyp... more The present study investigated the lipolytic (break of fat stored) effect of a citrus-based polyphenolic dietary supplement (SINETROL) at human adipocytes (ex vivo), body fat (clinical) and biochemical levels (inhibition of phosphodiesterase). Free fatty acids (FFA) release was used as indicator of human adipocyte lipolysis and SINETROL activity has been compared with known lipolytic products (isoproterenol, theopylline and caffeine). SINETROL stimulated significantly the lipolytic activity in a range of 6 fold greater than the control. Moreover, SINETROL has 2.1 greater activity than guarana 12% caffeine while its content in caffeine is 3 times lower. Clinically, two groups of 10 volunteers with BMI relevant of overweight were compared during 4 and 12 weeks with 1.4 g/day SINETROL and placebo supplementation. In the SINETROL Group the body fat (%) decreased with a significant difference of 5.53% and 15.6% after 4 and 12 weeks, respectively, while the body weight (kg) decreased with...

Research paper thumbnail of Clinical Study to Assess the Efficacy and Safety of a Citrus Polyphenolic Extract of Red Orange, Grapefruit, and Orange (Sinetrol-XPur) on Weight Management and Metabolic Parameters in Healthy Overweight Individuals

Phytotherapy Research, 2014

The present study investigated the efficacy and safety effects of Sinetrol-XPur (polyphenolic cit... more The present study investigated the efficacy and safety effects of Sinetrol-XPur (polyphenolic citrus dry extract) in weight management; metabolic parameters; and inflammatory, glycemic and oxidative status. In a 12-week, randomized, double-blind, placebo-controlled trial, Sinetrol-XPur was given to overweight subjects twice daily with meals in the tested group (N = 47) versus a placebo group (N = 48). Waist and hip circumference and abdominal fat were decreased in the Sinetrol-XPur group as compared with the placebo group (p < 0.0001) (-5.71% vs. -1.56% for waist, -4.71% vs. -1.35% for hip and -9.73% vs. -3.18% for fat). Inflammatory markers were reduced (C-reactive protein: -22.87% vs. +61%; fibrinogen: -19.93% vs. -1.61%, p < 0.01). Oxidative stress was lowered as seen by the reduction of malondialdehyde (-14.03% vs. 2.76%) and the increase in superoxide dismutase and glutathione (17.38% vs. 2.19% and 4.63% vs. -2.36%, respectively, p < 0.01). No adverse effects were observed. Kidney, liver, and lipid panels remained unchanged. These results indicated that Sinetrol-XPur supplementation is a viable option for reducing abdominal fat, waist and hip circumference, and body weight and for improving inflammatory, glycemic, and oxidative status in healthy overweight individuals.

Research paper thumbnail of Dietary docosahexaenoic acid-enriched glycerophospholipids exert cardioprotective effects in ouabain-treated rats via physiological and metabolic changes

Food Funct., 2015

Docosahexaenoic acid (DHA) might prevent heart failure or optimise drug treatments by improving c... more Docosahexaenoic acid (DHA) might prevent heart failure or optimise drug treatments by improving cardiac contraction. We investigated whether DHA-enriched avian glycerophospholipids (GPL-DHA) exert cardioprotection in ouabain-treated rats after 4 weeks of dietary supplementation with 10, 35 or 60 mg DHA per kg body weight versus none (DHA10, DHA35, DHA60 and control groups, respectively). The contractile responsiveness to different doses of ouabain (10(-7) to 10(-4) M), ouabain intoxication (at 3 × 10(-4) M), and relative variations in cardiac energy metabolism were determined using (31)P NMR in isolated perfused rat hearts. The fatty acid composition of cardiac membranes was analysed by gas chromatography. DHA accretion in the heart was dose-dependent (+8%, +30% and +45% for DHA10, DHA35 and DHA60, respectively). The cardiac phosphocreatine content significantly increased at the baseline in DHA35 (+45%) and DHA60 groups (+85%), and at the different doses of ouabain in the DHA60 group (+73% to 98%). The maximum positive inotropy achieved at 10(-4) M ouabain was significantly increased in all DHA groups versus control (+150%, +122.5% and +135% for DHA10, DHA35 and DHA60, respectively), and ouabain intoxication was delayed. The increase in myocardial phosphocreatine content and the improved efficacy of ouabain on myocardial contraction without toxicity suggest the potential of GPL-DHA as a dietary supplement or ingredient for functional food, and possibly as a co-treatment with digitalis drugs in humans.

Research paper thumbnail of At Low Doses, a g-Linolenic Acid-Lipoic Acid Conjugate Is More Effective Than Docosahexaenoic Acid-Enriched Phospholipids in Preventing Neuropathy in Diabetic Rats1

A deficiency in essential fatty acid metabolism has been reported in diabetes. Nutritional supple... more A deficiency in essential fatty acid metabolism has been reported in diabetes. Nutritional supplementations with (n-6) or (n-3) PUFA have differential efficiency on parameters of diabetic neuropathy, including nerve conduction velocity (NCV) and nerve blood flow (NBF). The aim of this study was to compare the neuroprotective effects of g-linolenic acid (GLA)- lipoic acid (LA) conjugate (GLA-LA) and docosahexaenoic acid

Research paper thumbnail of Effect of dietary α-linolenic acid on functional characteristic of Na+/K+-ATPase isoenzymes in whole brain membranes of weaned rats

Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism, 1993

ABSTRACT The influence of dietary fatty acids on Na+ sensitivity and ouabain affinity of Na+/K(+)... more ABSTRACT The influence of dietary fatty acids on Na+ sensitivity and ouabain affinity of Na+/K(+)-ATPase isoenzymes of whole brain membranes were studied in weaned rats fed for two generations with diets either devoid of alpha-linolenic acid (sunflower oil diet) or rich in alpha-linolenic acid (soya oil diet). The (n--3) deficiency induced by the sunflower oil diet led to an increase in the (n--6)/(n--3) molar ratio in whole brain membranes. Na+/K(+)-ATPase isoenzymes were discriminated on the basis of their differential affinities for ouabain. In rats fed sunflower oil diet, the ouabain titration displayed three inhibitory processes with markedly different affinities: low affinity (alpha 1); high affinity (alpha 2); and very high affinity (alpha 3). Membranes of rats fed soya oil diet exhibited only two inhibitory processes, i.e., low affinity (likely alpha 1+ alpha 2) and high affinity (likely alpha 2+ alpha 3) with the low affinity form intermediate between the sunflower alpha 1 and alpha 2 forms, and the high affinity form intermediate between the sunflower alpha 2 and alpha 3 forms. In fact, the Na+ response shows that the three isoenzymes have different Na+ sensitivities. Regardless of the diet, alpha 1 has a similar Na+ sensitivity (less than 1 mM), whilst alpha 2 and alpha 3 are more sensitive in soya oil membranes compared to sunflower oil membranes (5.1 vs. 7.2 mM and about 11 vs. 22.5 mM, respectively). Thus, sodium appears to be a better criterion of heterogeneity than ouabain.

Research paper thumbnail of At low doses, a gamma-linolenic acid-lipoic acid conjugate is more effective than docosahexaenoic acid-enriched phospholipids in preventing neuropathy in diabetic rats

The Journal of nutrition, 2007

A deficiency in essential fatty acid metabolism has been reported in diabetes. Nutritional supple... more A deficiency in essential fatty acid metabolism has been reported in diabetes. Nutritional supplementations with (n-6) or (n-3) PUFA have differential efficiency on parameters of diabetic neuropathy, including nerve conduction velocity (NCV) and nerve blood flow (NBF). The aim of this study was to compare the neuroprotective effects of gamma-linolenic acid (GLA)-lipoic acid (LA) conjugate (GLA-LA) and docosahexaenoic acid (DHA)-enriched phospholipids (PL) supplementations on NCV and NBF. Streptozotocin-induced diabetic (D) and control (C) rats were supplemented for 8 wk with either DHA-enriched PL at a dose of 30 mg.kg-1.d-1 (DDHA and CDHA) or with corn oil enriched with GLA-LA at a dose of 30 mg.kg-1.d-1 (DGLA and CGLA). Moreover, a C and D group received no supplementation. After 8 wk, NCV (-30%) and NBF (-50%) were lower in the D group than in the C group. Supplementation with GLA-LA totally prevented the decrease in NCV and NBF in the DGLA group, in which values did not differ f...

Research paper thumbnail of Ginkgo biloba extract (EGb 761) protects Na,K-ATPase isoenzymes during cerebral ischemia

Cellular and molecular biology (Noisy-le-Grand, France), 2002

Disturbances of Na,K-ATPase activity are implicated in the pathophysiology of cerebral ischemia. ... more Disturbances of Na,K-ATPase activity are implicated in the pathophysiology of cerebral ischemia. Previous experiments have shown that EGb 761 protects NaK-ATPase activity against one hour of cerebral ischemia. In the brain however, the 3 isoenzymes responsible for Na,K-ATPase activity may be differentially affected by various times of ischemia. In the present study, we investigated the effect of a longer period of ischemia, and the protection provided by a pre-treatment with EGb 761 on each of the 3 cerebral NaK-ATPase isoenzymes. In control and EGb 761 pre-treated mice exposed to a 6 hr unilateral occlusion of the middle cerebral artery, Na,K-ATPase activity was decreased by 60% and lipid peroxidation was increased by 40% in the ipsilateral (ischemic) cortex compared to the contralateral one. In parallel, membrane integrity was altered. The alteration of NaK-ATPase activity, as a whole, resulted from a decrease in the activity of the 3 isoenzymes. The two isoenzymes of high ouabain...

Research paper thumbnail of An organophosphorus compound, Vx, selectively inhibits the rat cardiac Na+,K+-ATPase α1 isoform Biochemical basis of the cardiotoxicity of Vx

Wcccivcd 4 Felxwry I99 I Scrincqxxitic re;lgcatr, an\iehulincstcruae orgnnophuwphtarux compounds ... more Wcccivcd 4 Felxwry I99 I Scrincqxxitic re;lgcatr, an\iehulincstcruae orgnnophuwphtarux compounds like Vx provoke, in the mieramahrr r:rngo, dipii&+likc vrntrieuhrr nr-rylhmiPs al' non-chalincrgic origin in rodent hrtrrrr. The arnsifivicirs uf Ihc two r:it cardiac Nu' ,K"-A'I'Posc is&xn~z (q und P:) RI Vx (O.l-IflO /rM) were mendurcd in xarcolcmmn vcsiclca. At I ,rM Vx, the inhibitian of the fotnl activity uvcrtlycd 18% bur never execcdcd 75~5 with I00 /IM, When the a) iaoform rietivity W:N inhihitcd by O,l ~rhl au&tCn, 11 wuo 3% inhibited by I rrM Vx, i.e. II 16&45 inhibition al the lute1 ueliviry,

Research paper thumbnail of Two functional Na+/K+-ATPase isoforms in the left ventricle of guinea pig heart

Guinea pig left ventricular muscle contains two distinct molecular forms of the N a + /K+-ATPase ... more Guinea pig left ventricular muscle contains two distinct molecular forms of the N a + /K+-ATPase catalytic a subunit. Sarcolemmal vesicles highly enriched in Na+/K+-ATPase were isolated by a new procedure that yielded specific activities of 60 -100 pmol Pi . h-' . mg-'. SDSjPAGE of isolated sarcolemma after reduction and alkylation of the sulfhydryl groups and identification on immunoblots with specific anti-(a subunit) antibodies indicated the presence of two major polypeptides of 100 kDa and 103 kDa, respectively. The two a subunits were functional: the dose/response curves of Na+/K+-ATPase activity with ouabain, dihydroouabain and digitoxigenin were biphasic, revealing the presence of high-affinity [concentration of drug causing 50% inhibition (IC50) = 10 nM] and low-affinity (ICs0 = 2 pM) forms with proportional contributions of 55% and 45%, respectively. The involvement of the high-affinity form in the positive inotropic effect of digitalis and of the low-affinity sites in both inotropy and toxicity are consistent with the literature data on rodents.

Research paper thumbnail of Na+/K+-ATPase Isoforms in Human Heart; Variation with Mammalian Species and Pathophysiological States

Research paper thumbnail of Non Effectiveness of Ouabain and Decrease in Na+/K+ -ATPase Affinity for Ouabain in Failing Rabbit Heart

Research paper thumbnail of A Quantitative Immunocytochemical Study of Na 1 ,K 1 ATPase in Rat Hepatocytes After STZ-induced Diabetes and Dietary Fish Oil Supplementation

Because diabetes causes alterations in hepatic membrane fatty acid content, these changes may aff... more Because diabetes causes alterations in hepatic membrane fatty acid content, these changes may affect the Na ϩ ,K ϩ -ATPase. In this study we documented the effects of streptozotocin (STZ)-induced diabetes on hepatic Na ϩ ,K ϩ -ATPase catalytic ␣ 1 -subunit and evaluated whether these changes could be normalized by fish oil supplementation. Two groups of diabetic rats received fish oil or olive oil supplementation. Both groups had a respective control group. We studied the localization of catalytic ␣ 1 -subunit on bile canalicular and basolateral membranes using immunocytochemical methods and confocal laser scanning microscopy, and the Na ϩ ,K ϩ -ATPase activity, membrane fluidity, and fatty acid composition on isolated hepatic membranes. A decrease in the ␣ 1 -subunit was observed with diabetes in the bile canalicular membranes, without changes in basolateral membranes. This decrease was partially prevented by dietary fish oil. Diabetes induces significant changes as documented by enzymatic Na ϩ ,K ϩ -ATPase activity, membrane fluidity, and fatty acid content, whereas little change in these parameters was observed after a fish oil diet. In conclusion, STZ-induced diabetes appears to modify bile canalicular membrane integrity and dietary fish oil partly prevents the diabetes-induced alterations. (J Histochem Cytochem 47:809-816, 1999)

Research paper thumbnail of Two functional Na+/K+-ATPase isoforms in the left ventricle of guinea pig heart

European Journal of Biochemistry, 1991

Guinea pig left ventricular muscle contains two distinct molecular forms of the N a + /K+-ATPase ... more Guinea pig left ventricular muscle contains two distinct molecular forms of the N a + /K+-ATPase catalytic a subunit. Sarcolemmal vesicles highly enriched in Na+/K+-ATPase were isolated by a new procedure that yielded specific activities of 60 -100 pmol Pi . h-' . mg-'. SDSjPAGE of isolated sarcolemma after reduction and alkylation of the sulfhydryl groups and identification on immunoblots with specific anti-(a subunit) antibodies indicated the presence of two major polypeptides of 100 kDa and 103 kDa, respectively. The two a subunits were functional: the dose/response curves of Na+/K+-ATPase activity with ouabain, dihydroouabain and digitoxigenin were biphasic, revealing the presence of high-affinity [concentration of drug causing 50% inhibition (IC50) = 10 nM] and low-affinity (ICs0 = 2 pM) forms with proportional contributions of 55% and 45%, respectively. The involvement of the high-affinity form in the positive inotropic effect of digitalis and of the low-affinity sites in both inotropy and toxicity are consistent with the literature data on rodents.

Research paper thumbnail of Modulation of mouse cerebral Na+,K+-ATPase activity by oxygen free radicals

NeuroReport, 1995

There is increasing evidence that oxygen free radicals (OFR) are involved in cerebral ischaemia-r... more There is increasing evidence that oxygen free radicals (OFR) are involved in cerebral ischaemia-reperfusion injury, possibly via a modulation of Na+,K(+)-ATPase activity, one of the major membrane pumps responsible for ionic homeostasis. We measured OFR-mediated modulation of this enzymatic activity and examined the roles of lipid and/or protein alterations. Using mouse brain microsomes exposed to UV-C irradiation, our results show a good correlation between activity inhibition and lipoperoxidation estimated by PUFA loss as well as malondialdehyde production. The protective effect of thiourea (OH scavenger) and the lack of effect noted with DTT (thiol protector) suggest that the functionality of the Na+,K(+)-ATPase is altered by perturbation of membrane integrity rather than by a structural alteration of the protein itself.

Research paper thumbnail of Dietary fish oil promotes positive inotropy and efficiency of digitalis

Lipids, 1999

Digitalis is clinically effective in heart failure, but it has an extremely narrow therapeutic in... more Digitalis is clinically effective in heart failure, but it has an extremely narrow therapeutic index. Inclusion of fish oil (FO) in the diet may have cardioprotective effects by different mechanisms (1,2): decreased heart rate and occurrence of arrhythmias, increased mechanical activity, and ejection fraction. The aim of this study was to investigate if dietary FO with incorporation of n-3 polyunsaturated

Research paper thumbnail of Canine Cardiac Digitalis Receptors are Preserved in Congestive Heart Failure Induced by Rapid Ventricular Pacing

Journal of Receptors and Signal Transduction, 1997

In dogs, it has been reported that acute ischemia or severe and terminal heart failure results in... more In dogs, it has been reported that acute ischemia or severe and terminal heart failure results in a selective reduction of myocardial alpha 3 isoform of Na, K-ATPase activity. The aim of this study was to evaluate if a similar change in the two canine digitalis receptor isoforms occurs following 4 weeks of rapid ventricular pacing-induced heart failure without profound necrosis. Heart failure was induced in dogs by rapid ventricular pacing (240 beats x min-1). Digitalis receptors were quantitated by [3H]-ouabain binding with isolated microsomal membranes from sham-operated (n = 3) and heart failure dogs (n = 4) and by Western blot analysis using specific alpha 1 and alpha 3 polyclonal antibodies. In kinetic studies, similar dissociation rates of 19 to 22 x 10(-4) s-1 and 1.3 to 2.4 x 10(-4) s-1 corresponding to high and low affinity sites respectively, were found in sham-operated and CHF dogs. Immunoblotting showed similar abundance of alpha 1 isoform in the two groups; however, levels of alpha 3 were increased by at least 50% in pacing-induced heart failure animals. In conclusion, heart failure selectively modulates the expression of cardiac alpha 3 isoform in dogs.

Research paper thumbnail of Beneficial effects of gamma linolenic acid supplementation on nerve conduction velocity, Na+, K+ ATPase activity, and membrane fatty acid composition in sciatic nerve of diabetic rats

The Journal of Nutritional Biochemistry, 1999

Metabolic and vascular abnormalities are implicated in the pathogenesis of diabetic neuropathy. T... more Metabolic and vascular abnormalities are implicated in the pathogenesis of diabetic neuropathy. Two principal metabolic defects are altered lipid metabolism resulting from the impairment of delta-6-desaturase, which converts linoleic acid (LA) into gamma linolenic acid (GLA), and reduced nerve Naϩ, Kϩ ATPase activity. This reduction may be caused by a lack of incorporation of (n-6) fatty acids in membrane phospholipids. Because this ubiquitous enzyme maintains the membrane electrical potential and allows repolarization, disturbances in its activity can alter the process of nerve conduction velocity (NCV). We studied the effects of supplementation with GLA (260 mg per day) on NCV, fatty acid phospholipid composition, and Naϩ, Kϩ ATPase activity in streptozotocin-diabetic rats. Six groups of 10 rats were studied. Two groups served as controls supplemented with GLA or sunflower oil (GLA free). Two groups with different durations of diabetes were studied: 6 weeks with no supplementation and 12 weeks supplemented with sunflower oil. To test the ability of GLA to prevent or reverse the effects of diabetes, two groups of diabetic rats were supplemented with GLA, one group for 12 weeks and one group for 6 weeks, starting 6 weeks after diabetes induction. Diabetes resulted in a 25% decrease in NCV (P Ͻ 0.0001), a 45% decrease in Naϩ, Kϩ ATPase activity (P Ͻ 0.0001), and an abnormal phospholipid fatty acid composition. GLA restored NCV both in the prevention and reversal studies and partially restored Naϩ, Kϩ ATPase activity in the preventive treatment group (P Ͻ 0.0001). These effects were accompanied by a modification of phospholipid fatty acid composition in nerve membranes. Overall, the results suggest that membrane fatty acid composition plays a direct role in NCV and confirm the beneficial effect of GLA supplementation in diabetic neuropathy. (J. Nutr. Biochem. 10: 411-420, 1999) . Effect of gamma linolenic acid supplementation on conduction velocity, Na/K ATPase activity and fatty acid phospholipid composition in sciatic nerve of diabetic rats.

Research paper thumbnail of Localization of Na,K-ATPase α/β Isoforms in Rat Sciatic Nerves : Effect of Diabetes and Fish Oil Treatment

Journal of Neurochemistry, 2002

The localization of the Na,K-ATPase isoenzymes in sciatic nerve remains controversial, as well as... more The localization of the Na,K-ATPase isoenzymes in sciatic nerve remains controversial, as well as diabetes-induced changes in Na,K-ATPase isoforms. Some of these changes could be prevented by fish oil therapy. The aim of this study was to determine by confocal microscopy the distribution of Na,K-ATPase isoforms (␣1, ␣2, ␣3, ␤1, and ␤2) in the sciatic nerve, the changes induced by diabetes, and the preventive effect of fish oil in diabetic neuropathy. This study was performed in three groups of rats. In the first two groups, diabetes was induced by streptozotocin and rats were supplemented daily with fish oil or olive oil at a dosage of 0.5 g/kg of body weight. The third one was a control group that was supplemented with olive oil. Five antibodies against specific epitopes of Na,K-ATPase isoenzymes were applied to stained dissociated nerve fibers with fluorescent secondary antibodies. The five isoenzymes were documented in nonspecific regions, Schwann cells (myelin), and the node of Ranvier. The localization of the ␣1, ␣2, and ␤1 isoenzymes was not affected by diabetes. In contrast, diabetes induced a decrease of the ␣2 subunit ( p Ͻ 0.05) and an up-regulation of the ␤2 subunit ( p Ͻ 0.05). These modifications were noted in both regions for ␣2 and were localized at the myelin domain only for the ␤2. Fish oil supplementation prevented the diabetesinduced changes in the ␣2 subunit with an additional up-regulation. The ␤2 subunit was not modified. A phenotypic change similar to nerve injury was induced by diabetes. Fish oil supplementation partially prevented some of these changes.

Research paper thumbnail of A 12-week randomized double-blind parallel pilot trial of Sinetrol XPur on body weight, abdominal fat, waist circumference, and muscle metabolism in overweight men

International Journal of Food Sciences and Nutrition, 2015

Overweight and obesity are associated to increased risk of developing non-communicable diseases t... more Overweight and obesity are associated to increased risk of developing non-communicable diseases that might dramatically affect life expectancy according World Health Organization. Overweight, obesity, and decline in physical activity are correlated to a significant propensity to lose skeletal muscle mass as a result of prolonged inflammation and oxidative stress whereas cohort surveys and clinical investigations have demonstrated health benefits of Citrus-based polyphenols to reverse such regression. Overweight men were included in a double-blind, randomized, parallel pilot trial where they received daily for a 12-week period 900 mg of a Citrus-based polyphenol extract, Sinetrol® XPur. Body composition, anthropometric, and blood parameters were assessed before and at the end of the intervention period. After 12 weeks, while the silhouette slimmed down, metabolic parameters were significantly improved and skeletal muscle catabolism held back. These data suggest that over a 12-week period, the efficacy of the supplement improve both overweight process and correlated skeletal muscle mass metabolism.

Research paper thumbnail of Regular consumption of Fiit-ns, a polyphenol extract from fruit and vegetables frequently consumed within the Mediterranean diet, improves metabolic ageing of obese volunteers: a randomized, double-blind, parallel trial

International journal of food sciences and nutrition, 2015

Epidemiological studies suggest that metabolic ageing process of overweight and obese populations... more Epidemiological studies suggest that metabolic ageing process of overweight and obese populations is associated with an increased risk of developing non-communicable diseases (NCDs). Inflammation, hyper-glycaemia, dyslipidemia and oxidative stress have been associated with early stages of NCDs development whereas cohort surveys have demonstrated health benefits of dietary polyphenols from various dietary sources to reverse such progress. Obese volunteers were included in a double-blind, randomized, parallel pilot trial where they received daily for a 12-week period 900 mg of a polyphenol-rich treatment extracted from fruit and vegetables frequently consumed within the Mediterranean diet. Anthropometric and blood parameters were assessed before and at the end of the intervention period. After 12 weeks, while the silhouette slimmed down, metabolic parameters were significantly improved and general satisfaction considerably ameliorated. These data suggest that over a 12-week period, th...

Research paper thumbnail of Lipolytic effect of a polyphenolic citrus dry extract of red orange, grapefruit, orange (SINETROL) in human body fat adipocytes. Mechanism of action by inhibition of cAMP-phosphodiesterase (PDE)

Phytomedicine : international journal of phytotherapy and phytopharmacology, 2008

The present study investigated the lipolytic (break of fat stored) effect of a citrus-based polyp... more The present study investigated the lipolytic (break of fat stored) effect of a citrus-based polyphenolic dietary supplement (SINETROL) at human adipocytes (ex vivo), body fat (clinical) and biochemical levels (inhibition of phosphodiesterase). Free fatty acids (FFA) release was used as indicator of human adipocyte lipolysis and SINETROL activity has been compared with known lipolytic products (isoproterenol, theopylline and caffeine). SINETROL stimulated significantly the lipolytic activity in a range of 6 fold greater than the control. Moreover, SINETROL has 2.1 greater activity than guarana 12% caffeine while its content in caffeine is 3 times lower. Clinically, two groups of 10 volunteers with BMI relevant of overweight were compared during 4 and 12 weeks with 1.4 g/day SINETROL and placebo supplementation. In the SINETROL Group the body fat (%) decreased with a significant difference of 5.53% and 15.6% after 4 and 12 weeks, respectively, while the body weight (kg) decreased with...

Research paper thumbnail of Clinical Study to Assess the Efficacy and Safety of a Citrus Polyphenolic Extract of Red Orange, Grapefruit, and Orange (Sinetrol-XPur) on Weight Management and Metabolic Parameters in Healthy Overweight Individuals

Phytotherapy Research, 2014

The present study investigated the efficacy and safety effects of Sinetrol-XPur (polyphenolic cit... more The present study investigated the efficacy and safety effects of Sinetrol-XPur (polyphenolic citrus dry extract) in weight management; metabolic parameters; and inflammatory, glycemic and oxidative status. In a 12-week, randomized, double-blind, placebo-controlled trial, Sinetrol-XPur was given to overweight subjects twice daily with meals in the tested group (N = 47) versus a placebo group (N = 48). Waist and hip circumference and abdominal fat were decreased in the Sinetrol-XPur group as compared with the placebo group (p < 0.0001) (-5.71% vs. -1.56% for waist, -4.71% vs. -1.35% for hip and -9.73% vs. -3.18% for fat). Inflammatory markers were reduced (C-reactive protein: -22.87% vs. +61%; fibrinogen: -19.93% vs. -1.61%, p < 0.01). Oxidative stress was lowered as seen by the reduction of malondialdehyde (-14.03% vs. 2.76%) and the increase in superoxide dismutase and glutathione (17.38% vs. 2.19% and 4.63% vs. -2.36%, respectively, p < 0.01). No adverse effects were observed. Kidney, liver, and lipid panels remained unchanged. These results indicated that Sinetrol-XPur supplementation is a viable option for reducing abdominal fat, waist and hip circumference, and body weight and for improving inflammatory, glycemic, and oxidative status in healthy overweight individuals.

Research paper thumbnail of Dietary docosahexaenoic acid-enriched glycerophospholipids exert cardioprotective effects in ouabain-treated rats via physiological and metabolic changes

Food Funct., 2015

Docosahexaenoic acid (DHA) might prevent heart failure or optimise drug treatments by improving c... more Docosahexaenoic acid (DHA) might prevent heart failure or optimise drug treatments by improving cardiac contraction. We investigated whether DHA-enriched avian glycerophospholipids (GPL-DHA) exert cardioprotection in ouabain-treated rats after 4 weeks of dietary supplementation with 10, 35 or 60 mg DHA per kg body weight versus none (DHA10, DHA35, DHA60 and control groups, respectively). The contractile responsiveness to different doses of ouabain (10(-7) to 10(-4) M), ouabain intoxication (at 3 × 10(-4) M), and relative variations in cardiac energy metabolism were determined using (31)P NMR in isolated perfused rat hearts. The fatty acid composition of cardiac membranes was analysed by gas chromatography. DHA accretion in the heart was dose-dependent (+8%, +30% and +45% for DHA10, DHA35 and DHA60, respectively). The cardiac phosphocreatine content significantly increased at the baseline in DHA35 (+45%) and DHA60 groups (+85%), and at the different doses of ouabain in the DHA60 group (+73% to 98%). The maximum positive inotropy achieved at 10(-4) M ouabain was significantly increased in all DHA groups versus control (+150%, +122.5% and +135% for DHA10, DHA35 and DHA60, respectively), and ouabain intoxication was delayed. The increase in myocardial phosphocreatine content and the improved efficacy of ouabain on myocardial contraction without toxicity suggest the potential of GPL-DHA as a dietary supplement or ingredient for functional food, and possibly as a co-treatment with digitalis drugs in humans.

Research paper thumbnail of At Low Doses, a g-Linolenic Acid-Lipoic Acid Conjugate Is More Effective Than Docosahexaenoic Acid-Enriched Phospholipids in Preventing Neuropathy in Diabetic Rats1

A deficiency in essential fatty acid metabolism has been reported in diabetes. Nutritional supple... more A deficiency in essential fatty acid metabolism has been reported in diabetes. Nutritional supplementations with (n-6) or (n-3) PUFA have differential efficiency on parameters of diabetic neuropathy, including nerve conduction velocity (NCV) and nerve blood flow (NBF). The aim of this study was to compare the neuroprotective effects of g-linolenic acid (GLA)- lipoic acid (LA) conjugate (GLA-LA) and docosahexaenoic acid

Research paper thumbnail of Effect of dietary α-linolenic acid on functional characteristic of Na+/K+-ATPase isoenzymes in whole brain membranes of weaned rats

Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism, 1993

ABSTRACT The influence of dietary fatty acids on Na+ sensitivity and ouabain affinity of Na+/K(+)... more ABSTRACT The influence of dietary fatty acids on Na+ sensitivity and ouabain affinity of Na+/K(+)-ATPase isoenzymes of whole brain membranes were studied in weaned rats fed for two generations with diets either devoid of alpha-linolenic acid (sunflower oil diet) or rich in alpha-linolenic acid (soya oil diet). The (n--3) deficiency induced by the sunflower oil diet led to an increase in the (n--6)/(n--3) molar ratio in whole brain membranes. Na+/K(+)-ATPase isoenzymes were discriminated on the basis of their differential affinities for ouabain. In rats fed sunflower oil diet, the ouabain titration displayed three inhibitory processes with markedly different affinities: low affinity (alpha 1); high affinity (alpha 2); and very high affinity (alpha 3). Membranes of rats fed soya oil diet exhibited only two inhibitory processes, i.e., low affinity (likely alpha 1+ alpha 2) and high affinity (likely alpha 2+ alpha 3) with the low affinity form intermediate between the sunflower alpha 1 and alpha 2 forms, and the high affinity form intermediate between the sunflower alpha 2 and alpha 3 forms. In fact, the Na+ response shows that the three isoenzymes have different Na+ sensitivities. Regardless of the diet, alpha 1 has a similar Na+ sensitivity (less than 1 mM), whilst alpha 2 and alpha 3 are more sensitive in soya oil membranes compared to sunflower oil membranes (5.1 vs. 7.2 mM and about 11 vs. 22.5 mM, respectively). Thus, sodium appears to be a better criterion of heterogeneity than ouabain.

Research paper thumbnail of At low doses, a gamma-linolenic acid-lipoic acid conjugate is more effective than docosahexaenoic acid-enriched phospholipids in preventing neuropathy in diabetic rats

The Journal of nutrition, 2007

A deficiency in essential fatty acid metabolism has been reported in diabetes. Nutritional supple... more A deficiency in essential fatty acid metabolism has been reported in diabetes. Nutritional supplementations with (n-6) or (n-3) PUFA have differential efficiency on parameters of diabetic neuropathy, including nerve conduction velocity (NCV) and nerve blood flow (NBF). The aim of this study was to compare the neuroprotective effects of gamma-linolenic acid (GLA)-lipoic acid (LA) conjugate (GLA-LA) and docosahexaenoic acid (DHA)-enriched phospholipids (PL) supplementations on NCV and NBF. Streptozotocin-induced diabetic (D) and control (C) rats were supplemented for 8 wk with either DHA-enriched PL at a dose of 30 mg.kg-1.d-1 (DDHA and CDHA) or with corn oil enriched with GLA-LA at a dose of 30 mg.kg-1.d-1 (DGLA and CGLA). Moreover, a C and D group received no supplementation. After 8 wk, NCV (-30%) and NBF (-50%) were lower in the D group than in the C group. Supplementation with GLA-LA totally prevented the decrease in NCV and NBF in the DGLA group, in which values did not differ f...

Research paper thumbnail of Ginkgo biloba extract (EGb 761) protects Na,K-ATPase isoenzymes during cerebral ischemia

Cellular and molecular biology (Noisy-le-Grand, France), 2002

Disturbances of Na,K-ATPase activity are implicated in the pathophysiology of cerebral ischemia. ... more Disturbances of Na,K-ATPase activity are implicated in the pathophysiology of cerebral ischemia. Previous experiments have shown that EGb 761 protects NaK-ATPase activity against one hour of cerebral ischemia. In the brain however, the 3 isoenzymes responsible for Na,K-ATPase activity may be differentially affected by various times of ischemia. In the present study, we investigated the effect of a longer period of ischemia, and the protection provided by a pre-treatment with EGb 761 on each of the 3 cerebral NaK-ATPase isoenzymes. In control and EGb 761 pre-treated mice exposed to a 6 hr unilateral occlusion of the middle cerebral artery, Na,K-ATPase activity was decreased by 60% and lipid peroxidation was increased by 40% in the ipsilateral (ischemic) cortex compared to the contralateral one. In parallel, membrane integrity was altered. The alteration of NaK-ATPase activity, as a whole, resulted from a decrease in the activity of the 3 isoenzymes. The two isoenzymes of high ouabain...

Research paper thumbnail of An organophosphorus compound, Vx, selectively inhibits the rat cardiac Na+,K+-ATPase α1 isoform Biochemical basis of the cardiotoxicity of Vx

Wcccivcd 4 Felxwry I99 I Scrincqxxitic re;lgcatr, an\iehulincstcruae orgnnophuwphtarux compounds ... more Wcccivcd 4 Felxwry I99 I Scrincqxxitic re;lgcatr, an\iehulincstcruae orgnnophuwphtarux compounds like Vx provoke, in the mieramahrr r:rngo, dipii&+likc vrntrieuhrr nr-rylhmiPs al' non-chalincrgic origin in rodent hrtrrrr. The arnsifivicirs uf Ihc two r:it cardiac Nu' ,K"-A'I'Posc is&xn~z (q und P:) RI Vx (O.l-IflO /rM) were mendurcd in xarcolcmmn vcsiclca. At I ,rM Vx, the inhibitian of the fotnl activity uvcrtlycd 18% bur never execcdcd 75~5 with I00 /IM, When the a) iaoform rietivity W:N inhihitcd by O,l ~rhl au&tCn, 11 wuo 3% inhibited by I rrM Vx, i.e. II 16&45 inhibition al the lute1 ueliviry,

Research paper thumbnail of Two functional Na+/K+-ATPase isoforms in the left ventricle of guinea pig heart

Guinea pig left ventricular muscle contains two distinct molecular forms of the N a + /K+-ATPase ... more Guinea pig left ventricular muscle contains two distinct molecular forms of the N a + /K+-ATPase catalytic a subunit. Sarcolemmal vesicles highly enriched in Na+/K+-ATPase were isolated by a new procedure that yielded specific activities of 60 -100 pmol Pi . h-' . mg-'. SDSjPAGE of isolated sarcolemma after reduction and alkylation of the sulfhydryl groups and identification on immunoblots with specific anti-(a subunit) antibodies indicated the presence of two major polypeptides of 100 kDa and 103 kDa, respectively. The two a subunits were functional: the dose/response curves of Na+/K+-ATPase activity with ouabain, dihydroouabain and digitoxigenin were biphasic, revealing the presence of high-affinity [concentration of drug causing 50% inhibition (IC50) = 10 nM] and low-affinity (ICs0 = 2 pM) forms with proportional contributions of 55% and 45%, respectively. The involvement of the high-affinity form in the positive inotropic effect of digitalis and of the low-affinity sites in both inotropy and toxicity are consistent with the literature data on rodents.

Research paper thumbnail of Na+/K+-ATPase Isoforms in Human Heart; Variation with Mammalian Species and Pathophysiological States

Research paper thumbnail of Non Effectiveness of Ouabain and Decrease in Na+/K+ -ATPase Affinity for Ouabain in Failing Rabbit Heart

Research paper thumbnail of A Quantitative Immunocytochemical Study of Na 1 ,K 1 ATPase in Rat Hepatocytes After STZ-induced Diabetes and Dietary Fish Oil Supplementation

Because diabetes causes alterations in hepatic membrane fatty acid content, these changes may aff... more Because diabetes causes alterations in hepatic membrane fatty acid content, these changes may affect the Na ϩ ,K ϩ -ATPase. In this study we documented the effects of streptozotocin (STZ)-induced diabetes on hepatic Na ϩ ,K ϩ -ATPase catalytic ␣ 1 -subunit and evaluated whether these changes could be normalized by fish oil supplementation. Two groups of diabetic rats received fish oil or olive oil supplementation. Both groups had a respective control group. We studied the localization of catalytic ␣ 1 -subunit on bile canalicular and basolateral membranes using immunocytochemical methods and confocal laser scanning microscopy, and the Na ϩ ,K ϩ -ATPase activity, membrane fluidity, and fatty acid composition on isolated hepatic membranes. A decrease in the ␣ 1 -subunit was observed with diabetes in the bile canalicular membranes, without changes in basolateral membranes. This decrease was partially prevented by dietary fish oil. Diabetes induces significant changes as documented by enzymatic Na ϩ ,K ϩ -ATPase activity, membrane fluidity, and fatty acid content, whereas little change in these parameters was observed after a fish oil diet. In conclusion, STZ-induced diabetes appears to modify bile canalicular membrane integrity and dietary fish oil partly prevents the diabetes-induced alterations. (J Histochem Cytochem 47:809-816, 1999)

Research paper thumbnail of Two functional Na+/K+-ATPase isoforms in the left ventricle of guinea pig heart

European Journal of Biochemistry, 1991

Guinea pig left ventricular muscle contains two distinct molecular forms of the N a + /K+-ATPase ... more Guinea pig left ventricular muscle contains two distinct molecular forms of the N a + /K+-ATPase catalytic a subunit. Sarcolemmal vesicles highly enriched in Na+/K+-ATPase were isolated by a new procedure that yielded specific activities of 60 -100 pmol Pi . h-' . mg-'. SDSjPAGE of isolated sarcolemma after reduction and alkylation of the sulfhydryl groups and identification on immunoblots with specific anti-(a subunit) antibodies indicated the presence of two major polypeptides of 100 kDa and 103 kDa, respectively. The two a subunits were functional: the dose/response curves of Na+/K+-ATPase activity with ouabain, dihydroouabain and digitoxigenin were biphasic, revealing the presence of high-affinity [concentration of drug causing 50% inhibition (IC50) = 10 nM] and low-affinity (ICs0 = 2 pM) forms with proportional contributions of 55% and 45%, respectively. The involvement of the high-affinity form in the positive inotropic effect of digitalis and of the low-affinity sites in both inotropy and toxicity are consistent with the literature data on rodents.

Research paper thumbnail of Modulation of mouse cerebral Na+,K+-ATPase activity by oxygen free radicals

NeuroReport, 1995

There is increasing evidence that oxygen free radicals (OFR) are involved in cerebral ischaemia-r... more There is increasing evidence that oxygen free radicals (OFR) are involved in cerebral ischaemia-reperfusion injury, possibly via a modulation of Na+,K(+)-ATPase activity, one of the major membrane pumps responsible for ionic homeostasis. We measured OFR-mediated modulation of this enzymatic activity and examined the roles of lipid and/or protein alterations. Using mouse brain microsomes exposed to UV-C irradiation, our results show a good correlation between activity inhibition and lipoperoxidation estimated by PUFA loss as well as malondialdehyde production. The protective effect of thiourea (OH scavenger) and the lack of effect noted with DTT (thiol protector) suggest that the functionality of the Na+,K(+)-ATPase is altered by perturbation of membrane integrity rather than by a structural alteration of the protein itself.

Research paper thumbnail of Dietary fish oil promotes positive inotropy and efficiency of digitalis

Lipids, 1999

Digitalis is clinically effective in heart failure, but it has an extremely narrow therapeutic in... more Digitalis is clinically effective in heart failure, but it has an extremely narrow therapeutic index. Inclusion of fish oil (FO) in the diet may have cardioprotective effects by different mechanisms (1,2): decreased heart rate and occurrence of arrhythmias, increased mechanical activity, and ejection fraction. The aim of this study was to investigate if dietary FO with incorporation of n-3 polyunsaturated

Research paper thumbnail of Canine Cardiac Digitalis Receptors are Preserved in Congestive Heart Failure Induced by Rapid Ventricular Pacing

Journal of Receptors and Signal Transduction, 1997

In dogs, it has been reported that acute ischemia or severe and terminal heart failure results in... more In dogs, it has been reported that acute ischemia or severe and terminal heart failure results in a selective reduction of myocardial alpha 3 isoform of Na, K-ATPase activity. The aim of this study was to evaluate if a similar change in the two canine digitalis receptor isoforms occurs following 4 weeks of rapid ventricular pacing-induced heart failure without profound necrosis. Heart failure was induced in dogs by rapid ventricular pacing (240 beats x min-1). Digitalis receptors were quantitated by [3H]-ouabain binding with isolated microsomal membranes from sham-operated (n = 3) and heart failure dogs (n = 4) and by Western blot analysis using specific alpha 1 and alpha 3 polyclonal antibodies. In kinetic studies, similar dissociation rates of 19 to 22 x 10(-4) s-1 and 1.3 to 2.4 x 10(-4) s-1 corresponding to high and low affinity sites respectively, were found in sham-operated and CHF dogs. Immunoblotting showed similar abundance of alpha 1 isoform in the two groups; however, levels of alpha 3 were increased by at least 50% in pacing-induced heart failure animals. In conclusion, heart failure selectively modulates the expression of cardiac alpha 3 isoform in dogs.

Research paper thumbnail of Beneficial effects of gamma linolenic acid supplementation on nerve conduction velocity, Na+, K+ ATPase activity, and membrane fatty acid composition in sciatic nerve of diabetic rats

The Journal of Nutritional Biochemistry, 1999

Metabolic and vascular abnormalities are implicated in the pathogenesis of diabetic neuropathy. T... more Metabolic and vascular abnormalities are implicated in the pathogenesis of diabetic neuropathy. Two principal metabolic defects are altered lipid metabolism resulting from the impairment of delta-6-desaturase, which converts linoleic acid (LA) into gamma linolenic acid (GLA), and reduced nerve Naϩ, Kϩ ATPase activity. This reduction may be caused by a lack of incorporation of (n-6) fatty acids in membrane phospholipids. Because this ubiquitous enzyme maintains the membrane electrical potential and allows repolarization, disturbances in its activity can alter the process of nerve conduction velocity (NCV). We studied the effects of supplementation with GLA (260 mg per day) on NCV, fatty acid phospholipid composition, and Naϩ, Kϩ ATPase activity in streptozotocin-diabetic rats. Six groups of 10 rats were studied. Two groups served as controls supplemented with GLA or sunflower oil (GLA free). Two groups with different durations of diabetes were studied: 6 weeks with no supplementation and 12 weeks supplemented with sunflower oil. To test the ability of GLA to prevent or reverse the effects of diabetes, two groups of diabetic rats were supplemented with GLA, one group for 12 weeks and one group for 6 weeks, starting 6 weeks after diabetes induction. Diabetes resulted in a 25% decrease in NCV (P Ͻ 0.0001), a 45% decrease in Naϩ, Kϩ ATPase activity (P Ͻ 0.0001), and an abnormal phospholipid fatty acid composition. GLA restored NCV both in the prevention and reversal studies and partially restored Naϩ, Kϩ ATPase activity in the preventive treatment group (P Ͻ 0.0001). These effects were accompanied by a modification of phospholipid fatty acid composition in nerve membranes. Overall, the results suggest that membrane fatty acid composition plays a direct role in NCV and confirm the beneficial effect of GLA supplementation in diabetic neuropathy. (J. Nutr. Biochem. 10: 411-420, 1999) . Effect of gamma linolenic acid supplementation on conduction velocity, Na/K ATPase activity and fatty acid phospholipid composition in sciatic nerve of diabetic rats.

Research paper thumbnail of Localization of Na,K-ATPase α/β Isoforms in Rat Sciatic Nerves : Effect of Diabetes and Fish Oil Treatment

Journal of Neurochemistry, 2002

The localization of the Na,K-ATPase isoenzymes in sciatic nerve remains controversial, as well as... more The localization of the Na,K-ATPase isoenzymes in sciatic nerve remains controversial, as well as diabetes-induced changes in Na,K-ATPase isoforms. Some of these changes could be prevented by fish oil therapy. The aim of this study was to determine by confocal microscopy the distribution of Na,K-ATPase isoforms (␣1, ␣2, ␣3, ␤1, and ␤2) in the sciatic nerve, the changes induced by diabetes, and the preventive effect of fish oil in diabetic neuropathy. This study was performed in three groups of rats. In the first two groups, diabetes was induced by streptozotocin and rats were supplemented daily with fish oil or olive oil at a dosage of 0.5 g/kg of body weight. The third one was a control group that was supplemented with olive oil. Five antibodies against specific epitopes of Na,K-ATPase isoenzymes were applied to stained dissociated nerve fibers with fluorescent secondary antibodies. The five isoenzymes were documented in nonspecific regions, Schwann cells (myelin), and the node of Ranvier. The localization of the ␣1, ␣2, and ␤1 isoenzymes was not affected by diabetes. In contrast, diabetes induced a decrease of the ␣2 subunit ( p Ͻ 0.05) and an up-regulation of the ␤2 subunit ( p Ͻ 0.05). These modifications were noted in both regions for ␣2 and were localized at the myelin domain only for the ␤2. Fish oil supplementation prevented the diabetesinduced changes in the ␣2 subunit with an additional up-regulation. The ␤2 subunit was not modified. A phenotypic change similar to nerve injury was induced by diabetes. Fish oil supplementation partially prevented some of these changes.

Research paper thumbnail of CV ANGL 2017.doc

Biological activity and biotechnology of lipids, pharmacology and physiopathology of diabetic com... more Biological activity and biotechnology of lipids, pharmacology and physiopathology of diabetic complication, • Nutritional influence of (n-3) polyunsaturated fatty acids on the Functional Properties of brain isoenzymes of Na +, K ATPase. (Neurosciences, animal Experiment animal, functional Studies of Na,K-ATPase by enzymology). THESIS • Origin and Purification of Endonenous digitalis like during the Development in the Brain, Kidney, Bowel and suprarenal Glands of the Rat. (Animal Experiment, anatomy, Extraction of tissue, HPLC, enzymological dosage) 1988-1989 Master degree (Paris XI) Speciality: structure and functioning of biologic integrated systems " (Paris XI) Options: structural and functional Studies of proteins and menbraneous complex, Cardiology. Laboratory " Pharmacology of the Ionic transport and membrane receptor " , Paris V Paris VII university, Place Jussieu. Prof. Lionel Lelièvre • Sodium sensitivity of the catalytic sub-unit of Na,K-ATPase isozenzymes. MEMORY • Pharmacology of digitaliques and toxicology of an Organosphorous agent (Vx) on a membrane complex (Na, K-ATPase Enzymology) • Preventive attempt of the nutrition in the diabetic neuropahy : Influence of fish oil (MaxEPA), the DHA (acid Docosahexenoïcue), the γ F 0 2 0 F 0 2 0-linolenic acid and the alpha lipoïc-γ linolenic. (Neuroscience, Diabetology, animal Experiment, anatomy, Nutrition, nervous and endoneural physiology, nervous histology)