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Biomedical subjects

G Simard

Publications and source records attributed to G Simard.

At least 19 recordsLinked to original sources
PubMed2005

Dexamethasone impairs muscle energetics, studied by (31)P NMR, in rats.

AIMS/HYPOTHESIS: Glucocorticoid treatments are associated with increased whole-body oxygen consumption. We hypothesised that an impairment of muscle energy metabolism can participate in this increased energy expenditure. METHODS: To investigate this possibility, we have studied muscle energetics of dexamethasone-treated rats (1.5 mg kg(-1) day(-1) for 6 days), in vivo by (31)P NMR spectroscopy. Results were compared with control and pair-fed (PF) rats before and after overnight fasting. RESULTS: Dexamethasone treatment resulted in decreased phosphocreatine (PCr) concentration and PCr:ATP ratio, increased ADP concentration and higher PCr to gamma-ATP flux but no change in beta-ATP to beta-ADP flux in gastrocnemius muscle. Neither 4 days of food restriction (PF rats) nor 24 h fasting affected high-energy phosphate metabolism. In dexamethasone-treated rats, there was an increase in plasma insulin and non-esterified fatty acid concentration. CONCLUSIONS/INTERPRETATION: We conclude that dexamethasone treatment altered resting in vivo skeletal muscle energy metabolism, by decreasing oxidative phosphorylation, producing ATP at the expense of PCr.

3-Hydroxybutyric Acid↗
PubMed2003

Description of microangiopathy in children with type 1 diabetes mellitus: a 19-year retrospective study.

BACKGROUND: The aim of the study was to estimate the outcome of patients with type 1 diabetes followed in a university hospital in the paediatric department and then in the adult diabetic department for at least 10 years. METHODS: We made a retrospective analysis of 50 patients (28 women and 22 men) with type 1 diabetes with disease duration of 19 +/- 6 years and analysed whether retinopathy and nephropathy had progressed, had remained unchanged or had improved or normalised. RESULTS: The mean age of diabetes onset was 8 +/- 4 years (1-16). Ketoacidosis revealed diabetes in 36% of the children. Mean HbA(1c) was 8.6 +/- 1.8%, and was over 8.5% in 34% of the patients. The mean age at onset of puberty (Tanner stage II) was 12 +/- 1 years in girls and 13 +/- 1 years in boys. Mean HbA(1c) was 7.9 +/- 1.2% during the year before onset of puberty and 8.7 +/- 1.1% in the following 3 years, corresponding to a 10% pubertal increase in HbA(1c). Retinopathy was seen in 50% of the patients at a mean age of 22 +/- 5 years, 15 +/- 6 years after onset of diabetes. Mean HbA(1c) was 9.7 +/- 1.6% in patients with proliferative retinopathy, 9.0 +/- 1.5% in patients with non proliferative retinopathy, and 8.1 +/- 1.3% in those without (p=0.02, proliferative versus no retinopathy, p > 0.05 non proliferative versus no retinopathy). Microalbuminuria was diagnosed in 26% of the patients. Mean HbA(1c) was 9.3 +/- 2.1% in patients with microalbuminuria versus 8.1 +/- 1.3% in those with normoalbuminuria (p=0.02). CONCLUSIONS: Glycemic control was similar in patients with non proliferative retinopathy and those without. Proliferative retinopathy and nephropathy were both related to the level of glycemic control.

Adolescent↗
PubMed2003

Effects of changes in water compartments on physiology and metabolism.

There is paramount evidence to suggest the importance of cell volume changes for the regulation of cell function, including protein metabolism. Among many other effects, cell swelling inhibits proteolysis and stimulates protein synthesis. However, most of the data pertinent to this theory relate to in vitro experiments. This paper reviews the evidence about the relevance of cell swelling and changes in water compartments to regulation of metabolism at the whole body level in animals and humans. Protein metabolism is most likely regulated by cellular hydration in health and disease. Cellular hydration appears to bear no effect on energy metabolism. The relationship between cellular hydration and lipolysis deserves to be verified. There appears to be a possible weak effect on glucose metabolism. Further studies are therefore necessary to challenge the cell swelling theory. If confirmed, strategies to modify cellular hydration could be used to improve metabolic orientations especially in the critically ill.

Animals↗
PubMed2002

[Thyroid hormones and obesity].

Although the stimulating effect of thyroid hormones on energy metabolism has been recognized for more than a century, the relation between thyroid function and weight control and obesity remains unclear. We review here the effects of thyroid hormones, hyperthyroidism, and hypothyroidism on body composition and the parameters of energy metabolism.

Animals↗
PubMed2001

Acute postural adaptations induced by a shoe lift in idiopathic scoliosis patients.

The objective of this study was to identify acute spinal and three-dimensional postural adaptations induced by a shoe lift in a population of idiopathic scoliosis (IS) patients. Forty-six IS patients (mean age: 12 +/- 2 years) were evaluated radiologically and with a stereovideographic system for pelvic obliquity. Based on the initial postural and radiological evaluation, a pertinent shoe lift height was chosen for each with the result that 12 patients were tested with 5-mm (S5) lifts, 20 patients were tested with 10-mm (S10) lifts, and 14 patients with 15-mm (S15) lifts. The posture for all 46 patients was then re-evaluated and a spinal radiograph obtained for 14 patients. The implementation of a shoe lift independent of the type of curve and amplitude significantly decreased the Cobb angle. As expected there was a change in the vertical height of the left tibial plateau and greater trochanter that induced a change in pelvic tilt. There was also a significant increase in the vertical height of S1 and T1. There was a significant change in the left and right iliac bone version, as well as a decrease in the difference in version between these two bones. The implementation of the shoe lifts also changed the lateral shift of the pelvis. A relative change between the shoulders and pelvis for tilt and anteroposterior shift was also found to be significant. In conclusion, using a shoe lift resulted in acute postural adaptations which specifically affected the spine and the three-dimensional position and orientation of the pelvis and shoulder girdle.

Adaptation, Physiological↗
PubMed2000

A noninvasive anthropometric technique for measuring kyphosis and lordosis: an application for idiopathic scoliosis.

STUDY DESIGN: Cross-sectional measurement of the sagittal geometry of adolescent idiopathic scoliosis patients. OBJECTIVES: To evaluate the accuracy of a noninvasive anthropometric approach for the measurement of kyphosis and lordosis. SUMMARY OF BACKGROUND DATA: Noninvasive approaches were developed to estimate the sagittal curvatures of the spine. However, the magnitude of the estimation error could be high for an important proportion of patients, which leads to a difficult clinical application. METHODS: The group was composed of 124 female patients with a mean age of 13.5 years (SD 2. 7 years) with Cobb angles ranging from 4 degrees to 66 degrees. Kyphosis and lordosis were measured on the lateral radiograph. The spine sagittal curvature of the same patients was also estimated using the spatial localization of skin markers placed overlying the spinous processes. These coordinates served as input into a simple trigonometric model. Data were collected by means of a stereovideographic technique (Motion Analysis Corp., Santa Rosa, CA). RESULTS: The intraclass correlation coefficient between both approaches was 0.94 for kyphosis and 0.91 for lordosis; the mean absolute differences were 5 degrees (SD 4 degrees ) and 6 degrees (SD 6 degrees ), respectively. The difference was less than 10 degrees in 91% of the patients for kyphosis, and in 79% for lordosis. CONCLUSIONS: The proposed technique appears to give more representative results than those presented in the literature. It has the advantage of being part of a global noninvasive postural evaluation. Using this approach in a systematic manner could help reduce radiograph exposure while keeping track of the spine sagittal curvatures.

Adolescent↗
PubMed2000

Lack of relationship in long-term type 1 diabetic patients between diabetic nephropathy and polymorphisms in apolipoprotein epsilon, lipoprotein lipase and cholesteryl ester transfer protein. Genétique de la Nephropathie Diabétique Study Group. Données Epidémiologiques sur le Syndrome d'Insulino-Résistance Study Group.

BACKGROUND: Genetic susceptibility contributes to the risk of diabetic nephropathy. Lipid disorders may favour diabetic nephropathy. Thus polymorphisms in lipid metabolism are candidates for the genetic component of risk for diabetic nephropathy. METHODS: We searched for a contribution of the genetic polymorphisms of lipoprotein lipase (LPL), cholesteryl ester transfer protein (CETP) and apolipoprotein epsilon (Apo E) to the development of diabetic nephropathy by studying 494 type 1 diabetic patients with proliferative retinopathy and various stages of diabetic nephropathy (GENEDIAB Study). The selection process ensured that all patients had expressed their risk of chronic complications due to uncontrolled diabetes. Thus the nephropathy stages were largely influenced by genetic background. The lipid profile included fasting plasma total cholesterol (TC), triglycerides (TG), apolipoprotein A1 (Apo A1) and B (Apo B), and lipoprotein (a) (Lp(a)). Genetic polymorphisms were determined by PCR-based detection of Apo epsilon (e2/e3/e4), LPL (mutation Asn 291 Ser) and CETP (TAQ:IB B1/B2). RESULTS: One hundred and fifty-seven patients (32%) had no nephropathy, 104 (21%) incipient nephropathy, 126 (25%) established nephropathy and 107 (22%) advanced nephropathy. There was a significant relationship between the stages of diabetic nephropathy and TC (P=0.002), TG (P<0.0001), Apo B (P=0.0007) or Lp(a) (P=0. 038), but not Apo A1. However the genetic polymorphism distributions of LPL, CETP and Apo epsilon did not differ in terms of renal complications. The study power to reject the null hypothesis was 58% for the Apo epsilon genotypes. CONCLUSION: These results support no or only marginal effects of a genetic basis for lipid disturbances encountered in diabetic nephropathy.

Adult↗
PubMed1999

[Comparison of the reliability of two 3D acquisition systems used for the study of anthropometric and postural parameters].

The goal of this study is to compare the between trials and between session reliability of the postural geometry (PG) and anthropometrical evaluations, obtained by the FreePoint (FP) system and the Motion Analysis System (MA). The potential of automatization of the anthropometric evaluation is also evaluate through the comparison of height measurements obtained by the two 3D systems and traditional anthropometrical tools. The PG of 15 adult control subjects (x: 25 years, SD: 6) evaluated on two occasions (1 week interval) and a mannequin on one occasion were evaluated with both systems. Each evaluation involved the identification of 52 anatomical landmarks followed by the acquisition of 5 trials with each system. The 3 dimensional position of the anatomical landmarks serves to define a postural model including the shoulder girdle, spinous processes (T1 to S1), thorax, pelvis, lower extremities and base of support. Postural parameters were calculated, including rotations, tilts, versions, kyphosis, lordosis, right and left Cobb, anteroposterior shifts, (AP), mediolateral shifts (ML) and vertical heights. The between trials and between session results demonstrate a strong correspondence of the 15 anthropometric heights and the 20 postural parameters between the three systems, permitting the proposal of a broadened clinical utilisation of the FreePoint system. However, the validity of these measures is influenced by the reliability of the anthropometric landmarking, natural oscillation of the body and the intra-specific variation of the posture of each subject.

Adult↗
PubMed1996

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↗
PubMed1996

Effect of lipid transfer activity and lipolysis on low density lipoprotein (LDL) oxidizability: evidence for lipolysis-generated non-esterified fatty acids as inhibitors of LDL oxidation.

Low density lipoproteins (LDL) were modified in vitro in the presence of lipid transfer activity and lipolysis, which induced alterations in the size and lipid composition of LDL particles but not in their antioxidant content. Subsequently, modified LDL were oxidized with copper sulfate and the extent of LDL oxidation was evaluated. Lipid transfer activity alone, or in combination with lipolysis, led to a significant reduction of LDL oxidability as compared with starting homologous LDL. Furthermore, the combined effect of lipid transfers and lipolysis reduced LDL oxidability to a significantly greater extent than did lipid transfers alone. Consistent results were obtained by measuring either the formation of lipid peroxides, the appearance of thiobarbituric acid reactive substances (TBARS), the disappearance of polyunsaturated fatty acids (PUFA), or the generation of cholesterol oxides. Non-esterified fatty acids (NEFA) arose as putative candidates in reducing oxidation susceptibility of LDL: NEFA-containing LDL were less oxidizable; the enrichment of LDL with either oleic acid or linoleic acid reduced significantly their oxidability; the oxidation susceptibility of either in vitro modified LDL or LDL isolated from normal or analbuminemic patients significantly increased after reduction of their NEFA content with fatty acid-poor albumin. After NEFA depletion, small-sized LDL resulting from the combined effects of lipid transfer and triglyceride hydrolysis activities became more oxidizable than large-sized LDL treated with lipid transfer activity alone. In addition, the PUFA to total fatty acid ratio and the oxidability of modified LDL varied accordingly after NEFA depletion, showing that in the present study not only lipoprotein-bound NEFA but also the total fatty acid composition of LDL could account for alterations in their oxidability.

Chromatography, High Pressure Liquid↗
PubMed1995

Relationship between fat intake and glomerular filtration rate in normotensive insulin-dependent diabetic patients.

Glomerular hyperfiltration is a candidate marker for diabetic nephropathy in insulin-dependent diabetic patients since it can reflect elevated glomerular capillary pressure, a cause of glomerulosclerosis. We studied the potential contribution of several dietary components to glomerular hyperfiltration during a cross-sectional study of 110 consecutive normotensive, non-proteinuric insulin-dependent patients with respect to glomerular filtration rate (GFR) and food intake. GFR was measured using the 51Cr-EDTA plasma disappearance technique. Glomerular hyperfiltration was defined as GFR > 137 ml.min-1 1.73 m-2 (mean +2 SD of age-matched healthy controls). Food intake was recorded with a computer-assisted programme. Thirteen patients displaying glomerular hyperfiltration ingested more protein (1.60 +/- 37 vs 1.38 +/- 0.34 g.kg-1 body weight.day-1; p = 0.032) and more fat (1.70 +/- 0.54 vs 1.39 +/- 0.44 g.kg-1 body weight.day-1; p = 0.022) than other subjects, although their total energy intakes were similar. Univariate regression analysis showed that GFR was positively related to both protein (r = 0.28; p = 0.003) and fat (r = 0.25; p = 0.007) intakes and negatively related to age (r = -0.29; p = 0.002). Stepwise multivariate regression analysis indicated 2 independent determinants for GFR: age (F = 15.26) and fat intake (F = 13.15). Excess fat intake may contribute to glomerular hyperfiltration in insulin-dependent diabetes.

Adolescent↗
PubMed1991

Differential effects of lecithin and cholesterol on the immunoreactivity and conformation of apolipoprotein A-I in high density lipoproteins.

Recently identified epitopes in apoA-I define a distinct N-terminal region with a complex tertiary structure, characterized by multiple discontinuous epitopes. Other epitopes are constituted of short domains centered either on beta-turns or random coils or on the 22-mer amphipathic alpha-helices (Marcel, Y. L., Provost, P. R., Koa, H., Raffaï, E., Vu Dac, N., Fruchart, J.-C., and Rassart, E. (1991) J. Biol. Chem. 266, 3644-3653). The compared immunoreactivity of seven epitopes studies here in response first to delipidation of high density lipoprotein (HDL) apoA-I by detergents, and second to modifications of HDL lipid composition by phospholipase A2 or by enrichment in surface lipids demonstrates that apoA-I has a flexible conformation which is readily responsive to the nature and concentration of bound lipids and that the structure of lipid-free apoA-I is significantly different from that of HDL-bound apoA-I, possibly representing a condensed molecule with several masked domains. In HDL apoA-I, these epitopes define five distinct domains which are characterized by particular responses to lipid modifications. However, two domains, each starting at the N-terminal beta-turn of an amphipathic alpha-helical repeat (residues 99-121 and 186-209, respectively) have almost identical immunoreactivity whether after detergent treatment or after changes in cholesterol and phospholipid levels, a property which probably reflects the known periodicity of apoA-I structural 22-mers. The immunoreactivity of a discontinuous epitope, representative of the N-terminal domain, is inversely related to the concentration of phospholipids, a unique characteristic among the epitopes tested here which indicates that the complex N-terminal region interacts with phospholipids, either directly or indirectly. These studies demonstrate that the conformation of multiple domains of HDL apoA-I is dependent on lipid phase composition and differentially affected by cholesterol and phospholipids.

Apolipoprotein A-I↗
PubMed1990

Kinetic evidence for phosphatidylethanolamine and triacylglycerol as preferential substrates for hepatic lipase in HDL subfractions: modulation by changes in the particle surface, or in the lipid core.

Human HDL subfractions, HDL2 (d: 1.085-1.125) and HDL3 (d: 1.125-1.19) labelled with 2-[14C]linoleoylphosphatidylethanolamine and tri-[3H]oleoylglycerol, were incubated with partially purified hepatic triacylglycerol lipase, isolated from human post-heparin plasma. Kinetics of hydrolysis of these two HDL-lipid substrates were followed and were compared to those previously obtained on phosphatidylcholine (G. Simard et al (1989) Biochim. Biophys. Acta 1001, 225-233). (1) The apparent Km obtained for HDL-triacylglycerol was half that for HDL-phosphatidylethanolamine, but the estimated Vmax was higher for the latter. Hence, despite a lower affinity, more molecules of phosphatidylethanolamine than of triacylglycerol were found hydrolysed. A strong correlation was observed between the hepatic lipase activity added and the maximal degradation rates for phosphatidylethanolamine measured in HDL2 and HDL3. (2) A linear relationship was observed in both HDL2 and HDL3 between the respective degradations of the two substrates. The number of phosphatidylethanolamine molecules hydrolysed exceeded that of triacylglycerol by 30% in HDL2 and by 70% in HDL3. HDL2 were 2- and 4-times more reactive than HDL3 for the hydrolysis of phosphatidylethanolamine and triacylglycerol, respectively, taking the Vmax/Km ratio as an indicator of catalytic efficiency. In both HDL subfractions, the calculated Vmax/Km value was 30-50-fold higher for PE and TG than for PC. (3) HDL particles were modified either on their surface by selective enrichment in free cholesterol or in their inner-core by replacement of esterified cholesterol by triacylglycerol in presence of a source of neutral lipid transfer activity. A mild cholesterol enrichment stimulated the phosphatidylethanolamine and triacylglycerol reactivities by 30-60% towards hepatic lipase, whereas increasing the triacylglycerol concentration in HDL was followed by a proportional increase in the amounts of triacylglycerol hydrolysed with no effect on phospholipid degradation.

Cholesterol↗
PubMed1990

Behaviour of phospholipase-modified HDL towards cultured hepatocytes. I. Enhanced transfers of HDL sterols and apoproteins.

Human HDL subfractions (HDL2, HDL3, or HDL separated by heparin affinity chromatography) were labelled either on their apolipoprotein moiety with 125I or on their sterols: unesterified [14C]cholesterol and [3H]cholesteryl linoleyl ether, a non-hydrolysable analog of esterified cholesterol. HDL subfractions were then treated with or without phospholipase A2 from Crotalus adamanteus in presence of albumin leading to a 72-82% phosphatidylcholine degradation. Control and treated HDL were reisolated and then addressed to cultured rat hepatocytes. (A) During incubations, unesterified [14C]cholesterol from HDL3 readily appeared in hepatocytes. The specific uptake of HDL esterified cholesterol calculated from [3H]cholesteryl ether was 2-4-times less important. Uptake of HDL cholesterol tended to saturate at 150-200 micrograms/ml HDL protein. A prior phospholipase treatment of HDL3 stimulated by 2-5-fold the uptake of [3H]cholesteryl ether, whereas the transfer of free [14C]cholesterol was minimally increased. The uptake of 3H/14C-labelled sterols from HDL2 was 2-3-times higher than from HDL3. (B) Parallel experiments were conducted with 125I-labelled HDL subfractions. At 37 degrees C, the specific uptake and degradation of HDL3 125I-apolipoprotein were about 2-fold enhanced following treatment of HDL3 with phospholipase A2. Uptakes of apolipoprotein and of esterified cholesterol were compared, indicating a preferential delivery of the sterol over apoprotein (X5). The dissociation was still more pronounced with phospholipase-treated HDL3. Competition experiments showed that 12-times more unlabelled HDL3 were required to half reduce the uptake of HDL3 [3H]cholesteryl ether than to impede similarly the HDL 125I-apolipoprotein recovered in cells. Uptake of 125I-labelled apolipoprotein from HDL2 was quantitatively comparable to that from HDL3. (C) Binding of 125I-HDL subfractions was followed at 4 degrees C. A specific binding was observed for HDL2 and HDL3, although kinetic parameters were quite different (KD of 9 and 25 micrograms/ml, respectively). Following phospholipolysis, both the specific and non-specific contributions to total binding were increased. Hence, hepatocytes take up more 125I-labelled apolipoprotein and 3H/14C-labelled sterols from lipolysed HDL than from unmodified particles. This is associated to changes in the binding characteristics.

Animals↗
PubMed1990

[Urinary excretion of albumin and lipid abnormalities in hypertensive insulin-dependent diabetics].

Patients with insulin dependent diabetes mellitus (IDDM) often suffer from cardiovascular diseases as renal failure occurs. Elevated albumin excretion rate (AER) is a predictive value of this event. Relations between AER, blood pressure, serum lipids and apoproteins concentrations in 100 patients with IDDM have been surveyed. Twenty one hypertensive patients (HT group) were compared to 21 patients without hypertension (n HT group), matched for sex, age, diabetes duration, and metabolic control, assessed by glycosylated haemoglobin. Comparison of both groups showed HT group had elevated systolic blood pressure (137 +/- 12 vs 126 +/- 20 mmHg; p less than .05), elevated diastolic blood pressure (80 +/- 7 vs 71 +/- 8 mmHg; p less than .001), increase in AER (27 range 3-4023 vs 6 range 2-51 mg/day; p less than .001), slightly elevated serum creatinine (95 +/- 32 vs 78 +/- 15 mumol/l; p less than .05). In HT group, serum lipid composition showed: raise in total cholesterol (251 +/- 43 vs 221 +/- 41 mg/dl; p less than 0.5), elevated apoprotein B (130 +/- 30 vs 99 +/- 21 mg/dl; p less than .001) elevated apoprotein B/apoprotein A1 ratio (.91 +/- .32 vs .66 +/- .27; p less than .001), elevated triglycerides (157 +/- 53 vs 98 +/- 43 mg/dl; p less than .005) and elevated LDL-cholesterol (170 +/- 42 vs 143 +/- 33 mg/dl; p less than .05). Levels of apoprotein A1 and HDL-cholesterol were not significantly different. Body mass index, daily insulin requirement and tobacco usage were similar in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

[Hepatic triglyceride lipase].

The post-heparin plasma contains two lipolytic enzymes. This review deals with the lesser known, hepatic triglyceride lipase. Like lipoprotein lipase, H-TGL is a glycoprotein and has an optimal pH of 8-9. But it does not require an activator protein and its activity is not inhibited by NaCl or protamine sulfate. Synthesized by the hepatocytes, H-TGL is located at the hepatic vascular endothelium. It catalyses the hydrolysis of a wide variety of lipid substrates including triacylglycerol and phospholipids. The function of the enzyme is still not fully known. H-TGL may function in the clearance of triglyceride rich lipoprotein remnants and in the catabolism of HDL.

Amino Acid Sequence↗