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Biomedical subjects

J F Brun

Publications and source records attributed to J F Brun.

At least 37 records · Page 2Linked to original sources

Reduction of fat accumulation and lipid disorders by individualized light aerobic training in human immunodeficiency virus infected patients with lipodystrophy and/or dyslipidemia.

BACKGROUND: The management of abdominal fat accumulation and metabolic disorders in HIV1-infected patients, by an aerobic training program, is considered. METHODS: Seventeen lipodystrophic and 2 dyslipidemic (without body modification) adults were studied before and after 4 months of training. The training load was individualized on a ventilatory threshold basis, determined during a maximal exercise test on cycle ergometer. Total (TAT), Visceral (VAT) and Subcutaneous Adipose Tissue (SAT) were assessed by CT-scan. Total (TC) and High Density Lipoprotein (HDL-C) Cholesterol, Triglycerides (TG), lactate (La), insulin and glucose were measured after a 12-hour-overnight fast. LDL, TC/HDL, TG/HDL, HOMA-insulin resistance index and coronary heart disease (CHD) relative risk (RR(CHD)) were calculated. RESULTS: Besides a significant improvement of aerobic fitness, trained patients exhibited a reduction in TAT (-12.8%, p < 0.001), specially at the visceral level (- 12%, p < 0.01) and in TC, TG and La (- 23%, - 43% and - 19% respectively, p < 0.01). HDL-C was increased (+ 6%, p < 0.01). All these effects were above changes that could be expected by a possible regression to the mean artefact. Both TC/HDL and TG/HDL were reduced (p < 0.01) and the estimated RR(CHD) decreased by approximately 13% (p < 0.01). No significant training effect was observed on the 9 available HOMAs. Significant correlations were found between changes in blood lipid values and baseline measures (r range - 0.55 to - 0.79, p < 0.05), indicating a larger improvement when baseline lipid parameters were higher. CONCLUSION: Aerobic training reduced visceral fat, lipid disorders, basal blood lactate and CHD markers in HIV patients. Training effects were particularly important for patients with marked dyslipidemia.

Adipose Tissue↗

Insulin and non-insulin-dependent glucose disposal in middle-aged and young athletes versus sedentary men.

The purpose of this study was to delineate the respective roles of aging and endurance training on glucose disposal. Thirty-two subjects (16 middle-aged men: 8 cyclists [MAcy], and 8 sedentary men [MAsed] and 16 young men: 8 cyclists [Ycy] and 8 sedentary men [Ysed]) were compared in this study. After overnight fasting, glucose was administered intravenously (0.5 g. kg(-1), 30% solution) and insulin-glucose interactions were assessed by measuring indices of insulin sensitivity (SI) and glucose effectiveness (Sg) using Bergman's minimal model. Sg includes basal insulin effectiveness (BIE) and glucose effectiveness at zero insulin (GEZI). Endurance training improved SI and Sg in all subjects, regardless of age (P <.05), but an increase in GEZI was found only in young men (P <.05). An effect of aging was found in sedentary subjects, who exhibited a lower SI (P <.05) when older. However, this effect disappeared with training, in which SI was nearly identical in young and middle-aged subjects. There was a correlation between SI and &Vdot;omicron(2max) in middle-aged men (r =.76, P <.01). These data suggest that the higher glucose uptake in endurance-trained male cyclists was mostly attributable to an increase in non-insulin-dependent glucose uptake in the young men and to an increase in its insulin-dependent component in the middle-aged men.

Adult↗

Streptozotocin-induced diabetes decreases rat sarcolemmal lactate transport.

Impaired lactate metabolism is a metabolic disorder, which is not fully understood in the diabetic state including streptozotocin (STZ)-induced diabetes. We investigated whether STZ-induced diabetes results in altered lactate exchanges using the rat muscle sarcolemmal vesicles (SV) model. Fifteen days after diabetes onset (1 STZ-injection, 65 mg/kg, intraperitoneal [IP]), rats had higher blood and muscle lactate concentrations compared with normal rats (1.50 +/- 0.09 v 1.95 +/- 0.21 mmol/L (not significant [NS]) and 21.02 +/- 1.26 v 25.53 +/- 0.98 mmol/kg wet weight (ww); P < .05). The initial rate of lactate uptake was measured at various external lactate concentrations using SV of both group in zero-trans conditions. STZ-induced diabetes decreased the initial rate of total lactate influx at external lactate concentrations from 1 to 100 mmol/L (P < .05). This decrease in lactate transport was found in addition to an increased free radical production, as indicated by a significant increase in malonedialdehyde (MDA) concentration (64.3 +/- 8.7 v 100.3 +/- 13.5 nmol. g(-1) ww, P < .05), coupled with a higher glutathione peroxidase (Gpx) activity (48.03 +/- 3.13 v 84.7 +/- 15.01 micromol. min(-1). mg(-1) protein, P < .05) in red gastrocnemius. We concluded that STZ-induced diabetes decreases total lactate transport activity in rat SV and is associated with increased muscular oxidative stress.

Animals↗

Exercise hypoglycemia in nondiabetic subjects.

Hypoglycemia during exercise is a common event due to an unbalance between training volume, nutrition, and external influences such as chronobiology, temperature or altitude, in subjects characterized by an acute and chronic increase in glucose effectiveness and insulin sensitivity. While it is preventable by adequate pre-exercise feeding with carbohydrates, it can also be induced by a prior carbohydrate meal with high glycemic index. Adequate training induces resistance to hypoglycemia via a shift in the balance of oxidized substrates and marked hormonal adaptations, but overtraining, by partially reversing this adaptation, favorizes hypoglycemia. Exercise hypoglycemia is a cause of fatigue or exercise cessation, but also impairs thermoregulatory adaptation and is assumed to fragilize muscles and tendons for traumatic events.

Dietary Carbohydrates↗

Balance of substrate oxidation during submaximal exercise in lean and obese people.

OBJECTIVES: To compare fat and carbohydrate oxidation at different exercise intensities between overweight and normal-weight subjects, in order to analyze the influence of muscular metabolic abnormalities in obese people on substrate utilization during exercise. MATERIAL AND METHODS: 32 healthy sedentary overweight subjects (Body Mass Index (BMI): 30.8 +/- 0.8 kg/m(2); body fat: 37.4 +/- 1.1%; mean +/- SEM) and 26 controls (BMI: 23 +/- 0.4 kg/m(2); body fat: 22.7 +/- 1.1%) matched for age and sex were examined. The test consisted in four six-min. submaximal steady-state workloads with calculation of substrate oxidation rates and derived quantitative parameters, i.e., crossover point (defined as the power at which carbohydrate-derived energy becomes predominant) and maximal fat oxidation rate point. In addition, the accuracy of the test was analyzed and was found to be satisfactory. RESULTS: While exercise intensities were similar in both group, fat oxidation rates were significantly lower in overweight group (p<0.05). The crossover and the maximal fat oxidation rate points were significantly lower in overweight subjects than in controls: 33.3 +/- 2 vs 50.1 +/- 3.4% and 30.5 +/- 2.3 vs 44.6 +/- 3.3% of maximal aerobic power, respectively (p<0.001). CONCLUSION: Sedentary overweight subjects, compared to controls at the same exercise intensities, exhibited an alteration of the balance of substrate oxidation, reflected by lower rates of fat oxidation and a shift of quantitative parameters to lower intensities. The test appeared to be reliable and could be of interest to advise an individualized exercise prescription in obese people.

Adult↗

Multivariate analysis of relationships between insulin sensitivity and blood rheology: is plasma viscosity a marker of insulin resistance?

We previously reported in populations exhibiting all the spectrum of insulin sensitivity (SI) values correlations between SI and blood viscosity eta suggesting that high eta is an additional symptom of the insulin resistance syndrome. However, due to the elevation of insulinemia (I) which is usually associated with insulin resistance it remained to determine whether this relationship was explained by SI or I. We analyzed SI with the minimal model procedure in 108 nondiabetic subjects and analyzed correlations of SI with blood rheology (eta, RBC aggregation and rigidity). Across quartiles of SI (defined after log transformation since distribution of SI was not normal), hematocrit and red cell rigidity remained stable, while aggregability and plasma viscosity (etap) increased in the lowest quartile. SI was correlated to only two rheological parameters: etap (r= -0.280, p=0.005) and Myrenne index M1 (r= -0.219, p=0.044). Among SI, I, age and BMI multivariate analysis selected only BMI as a determinant of either whole blood viscosity (etawb: r= -0.301, p=0.004) and RBC disaggregation threshold (gammaD: r= -0.331, p=0.013), only I as determinant of M1 (r=0.254, p=0.03), and a combination of BMI (p=0.009) and SI (p=0.007) for etap. Although age and obesity are factors of hyperviscosity, the hemorheological disturbances found in insulin resistance are not fully statistically "explained" by those two factors. While hyperaggregability (measured with M1) is rather related to hyperinsulinism, etap is influenced by SI and should be further investigated as a simple marker for the follow up of insulin-resistant states.

Adult↗

Lower limb vein enlargement and spontaneous blood flow echogenicity are normal sonographic findings during pregnancy.

PURPOSE: We studied pregnancy-induced changes in lower limb venous function. METHODS: We used plethysmography and sonography to assess the changes in venous wall distensibility, saphenous vein diameters, and spontaneous blood flow echogenicity in the common femoral veins in 190 consecutive women during and after uncomplicated pregnancies (total of 409 examinations). RESULTS: The percentage of women with clinical symptoms and signs of venous insufficiency increased significantly during pregnancy. The mean diameters of the great and small saphenous veins also increased significantly, while occlusive venous plethysmography showed a decrease in parameters indicating vein distensibility. Spontaneous blood flow echogenicity in the common femoral veins was clearly visible or marked in 6% of cases during the first trimester of pregnancy, 63% during the second trimester, and 96% during the third trimester, versus 6% after delivery (p < 0.0001). The mean hematocrit decreased and the mean fibrinogen concentration increased during pregnancy. CONCLUSIONS: The increase in lower limb venous pressure seen during pregnancy leads to venous overdistention and worsens blood stasis. Decreased venous flow velocity and rheological alterations result in increased red cell aggregation, giving rise to spontaneous blood flow echogenicity. Spontaneous blood flow echogenicity is therefore a normal finding during pregnancy and should not be mistaken for venous thrombosis.

Adult↗

The effects of exercise training intensification on glucose disposal in elite cyclists.

To assess the effect of training on glucose disposal, we performed a longitudinal study of 11 elite cyclists before and after 4 months of intensive training compared to 11 sedentary subjects. Insulin sensitivity (SI) and glucose effectiveness (Sg) were measured using Bergman's minimal model. Sg includes basal insulin effectiveness (BIE) and a parameter termed glucose effectiveness at zero insulin (GEZI). After overnight fasting glucose was administered intravenously (0.5 g x kg(-1), 30% solution given over 3 min), and insulin (0.02 U x kg(-1), 1 -2U) was injected immediately after 19 min. Sg, SI and BIE, were significantly higher in elite cyclists both before and after training than in sedentary subjects (P < 0.01). However, the non-insulin-dependent component of Sg (GEZI) was higher only after the intensive training in the cyclists (3.31 +/- 0.67% x min(-1)) than in sedentary subjects (1.7 +/- 0.2% x min(-1), P < 0.02). We conclude that insulin sensitivity (SI) and glucose effectiveness (Sg) are higher in elite cyclists than in sedentary subjects and that these high and almost optimal values are not further improved by additional training. However, the improvement in GEZI, as reflected by the difference between post-training GEZI and sedentary control values, raises the possibility of an increase of the non-insulin-mediated mobilization of glucose transporters.

Adult↗

Rheological properties of fetal red cells with special reference to aggregability and disaggregability analyzed by light transmission and laser backscattering techniques.

Blood viscosity factors and fetal erythrocyte aggregability were investigated with light transmission (Myrenne device) during a cross-sectional study of blood drawn in utero by cord venepunctures in 119 normal fetuses between 18 and 39 weeks gestation. There was a progressive increased blood viscosity at native hematocrit (p < 0.01) explained by a gradual increase in both hematocrit (from 33% to 40%, p < 0.05) and Dintenfass' 'Tk' RBC rigidity index (p < 0.05), while plasma viscosity remained constant at 1.18 +/- 0.01 mPa x s as well as the h/eta ratio (188.4 +/- 2.7 mPa(-1) x s(-1)). The RBC aggregation index 'M' remained almost equal to zero (mean value: 0.04 +/- 0.01) before 32 wk gestation and then increased (p < 0.05) until delivery. The upper physiological limit for this parameter before 32 wk (mean +/- 2 SD) is 0.18. The RBC aggregation index 'M1' remained constant during pregnancy at 2.98 +/- 0.26, i.e., the upper physiological limit for this parameter during the intrauterine life (mean +/- 2 SD) is 7.85. Both fibrinogen (r = 0.479, p < 0.05) and albumin (r = 0.494, p < 0.01) correlated with time so that the albumin/fibrinogen ratio remained stable. We then studied with the laser retrodiffusion technique the venous blood of 20 women (18-43 yr, 37-40 wk gestation) and the cord blood of their newborns at birth, comparing RBC aggregation of: mothers (M), maternal RBCs resuspended on newborn plasma (MF), newborn RBCs resuspended on maternal plasma (FM), and newborns (F). Aggregability is higher in M (RBC aggregation time M < MF < FM < F; p < 0.01); RBC aggregation index at 10 s M > MF > FM > F; p < 0.01), with in turn the symmetric inverse picture for the partial disaggregation threshold (M > MF = FM > F). Thus RBC disaggregability is higher in newborns, and suspensions on maternal and newborn plasma suggest that half of this difference in aggregability (and disaggregability) between fetal and adult blood results from plasma factors and another half from erythrocytes.

Adolescent↗

Aggregability and disaggregability of erythrocytes in women suffering from ovarian cancer: evidence for an increased disaggregation threshold.

In order to further characterize the alterations of erythrocyte aggregation described in ovarian cancer, we measured it with laser backscattering in eleven women suffering from ovarian cancer (mean age: 44.7 +/- 3.6, extreme values: 28-61 yr) compared with thirteen matched control women. Blood rheology exhibited a wide variability in cancer patients, with some unusually high values of plasma viscosity and/or RBC aggregation in individual cases. The only significant differences were found for the RBC disaggregation threshold which was higher in patients than in controls (78.06 +/- 10.14 vs 52.6 +/- 3.15 s(-1), p < 0.05), while hematocrit was lower (34.45 +/- 1.42 vs 38.23 +/- 0.75, p < 0.05). A negative correlation between hematocrit and corrected blood viscosity on the whole sample of subjects (r = 0.454, p < 0.05) indicates that hematocrit is decreased in subjects prone to high viscosity, resulting in similar values of apparent blood viscosity in controls and patients. Thus, a lower disaggregability of RBCs is evidenced in women with ovarian cancer, as well as a tendency to blood hyperviscosity compensated by a reduction of hematocrit which suggests that there may be some degree of 'viscoregulation'.

Blood Viscosity↗

100 mg acetylsalicylic acid acutely decreases red cell aggregation in women taking oral contraceptives.

Since oral contraceptives (OC) are known to impair blood fluidity and to increase the risk of venous and arterial thrombosis, while acetylsalicylic acid (ASA) decreases the thrombotic risk and modifies some rheologic parameters, we compared the hemorheologic effects of ASA on blood rheology between women treated by OC and women who never received this medication. 25 women under OC were compared to 25 matched women who had never used OC. Blood viscosity (MT90 viscometer) and RBC aggregation (Myrenne aggregometer and AFFIBIO erythroaggregometer) were measured before and 1 hr after women received per os 100 mg ASA, after an overnight fast. The only significant difference between women under OC and controls was an increased RBC aggregation ('M' index +28%, p < 0.04; Affibio aggregation time -21%, p < 0.03). On the whole sample of 50 women as well as in the subgroup of women under OC, ASA decreased RBC partial disaggregation threshold (-1.7%, p < 0.01). These results confirm that RBC aggregation is increased under OC and suggest that 100 mg ASA acutely induces a partial reversal of this RBC hyperaggregation.

Adult↗

Relationships between blood viscosity and insulin-like growth factor I status in athletes.

Exercise training is known (1) to enhance the function of the GH-IGF-I system, which has profound effects on body fluid status; (2) to increase blood fluidity. Thus, we investigated during an exercise-test in 39 male elite sportsmen (age 23.7+/-0.72 years; body mass index 23.7+/-0.28 kg/m2) the possible relationships between GH and IGF-I status and the rheological properties of blood. Two correlations indicate a relationship between body hydration and fitness: isometric handgrip strength is correlated with the percentage of extracellular water in total body water (r = 0.432, p = 0.02) and the aerobic working capacity W170 is negatively correlated with hematocrit (r = -0.341, p = 0.039). Water loss during exercise appears to be inversely related to fitness as evaluated by W170 (r = -0.529, p = 0.05), and is positively correlated with the score of signs of overtraining (r = 0.725, p = 0.003) and with the red blood cell aggregation index (r = 0.584, p = 0.036). Finally, while the GH peak value is correlated with the extracellular water volume (r = 0.393, p = 0.02), IGF-I is correlated with blood viscosity (r = 0.546, p = 0.0003), suggesting that when IGF-I values are within the upper quintile (>340 ng/ml) IGF-I may unfavourably affect blood rheology. Among factors of blood viscosity, IGF-I exhibits a borderline correlation (p = 0.05) with "Tk" and the ratio IGF1/IGFBP3 which reflects free circulating IGF-I is correlated with red cell aggregability measured with the Myrenne "M" (r = 0.485, p = 0.014) and S60 (r = 0.396, p = 0.494). These findings confirm the importance of hydration and dehydration as determinants of both blood rheology and exercise performance. Moreover, they suggest that values of IGF-I within the upper quintile are associated with an impairment of blood fluidity, possibly due to a direct effect of IGF-I on red cell deformability and aggregability.

Adult↗

The paradox of hematocrit in exercise physiology: which is the "normal" range from an hemorheologist's viewpoint?

The paradox of hematocrit in exercise physiology is that artificially increasing it by autotransfusion or erythropoietin doping improves VO2 max and performance, while in normal conditions there is a strong negative correlation between hematocrit and fitness, due to a training-induced "autohemodilution". We aimed at investigating: (a) which is the physiological range of hematocrit in highly trained professional footballers; (b) what are the characteristics of athletes with high vs low hematocrit? We determined in 77 healthy male footballers the physiological range (mean +/- sd) of hematocrit: 42.3+/-2.74, (range -2sigma/+2sigma = 36.8-47.8%) thus defining boundaries of quintiles of distribution for this parameter: 40, 41.6, 42.9, 44.6. In another sample of 42 male footballers we compared three groups: lowest quintile (n = 8), highest quintile (n = 5) and the three middle quintiles considered together (n = 29). Athletes in the lowest quintile compared to those in the four other quintiles had a lower value of blood viscosity (-8%, p < 0.01) but this difference disappeared after correction for hematocrit. These subjects with low hematocrit had also higher values of the following parameters: aerobic working capacity (p < 0.01); isometric adductor strength (p = 0.02); crossover point of carbohydrate oxidation (70% carbohydrates/30% lipids) (p < 0.05); insulin like growth factor binding protein 1 (p < 0.0001). Athletes in the highest quintile had higher red cell aggregability (Myrenne index "M1" 8.45+/-0.38 vs 6.82+/-0.62, p < 0.04) and a higher disaggregability threshold gammaD (72.6+/-22.63 vs 44.49+/-1.37, p < 0.01) and a lower percentage of water in fat-free mass (p < 0.02). On the whole sample hematocrit was negatively correlated with aerobic working capacity (W170 r = -0.329, p = 0.007; Wmax (% of expected value) r = -0.552, p = 0.008; VO2 max (% of expected value) r = -0.543, p = 0.009) and with ferritin (r = -0.33, p = 0.031), and positively correlated with the overtraining score (r = 0.352, p = 0.019) which was in turn negatively correlated with ferritin r = -0.312, p = 0.02). Besides, hematocrit behaves as a major determinant of blood viscosity (correlation with blood viscosity r = 0.997, p < 10(-7)) and erythrocyte disaggregability gammaD (r = 0.384, p = 0.03), but the hematocrit/viscosity ratio (h/eta index of O2 delivery) remains maintained almost constant over the range of values studied. These results show that (a) physiological values of hematocrit in these athletes are comprised between 36 and 48%; (b) "low" hematocrit (<40%) was associated with a higher aerobic capacity; (c) subjects with the higher hematocrits (>44.6%) were frequently overtrained and/or iron-deficient, and their blood viscosity (and red cell disaggregability) tended to be increased.

Adaptation, Physiological↗

Postprandial reactive hypoglycemia.

Postprandial reactive hypoglycemia (PRH) can be diagnosed if sympathetic and neuroglucopenic symptoms develop concurrently with low blood sugar (<3.3 mmol). Neither the oral glucose tolerance test (OGTT) nor mixed meals are suitable for this diagnosis, due to respectively false positive and false negative results. They should be replaced by ambulatory glycemic control or, as recently proposed, an hyperglucidic breakfast test. PRH patients often suffer from an associated adrenergic hormone postprandial syndrome, with potential pathologic consequences such as cardiac arrhythmia. PRH could result from (a) an exaggerated insulin response, either related to insulin resistance or to increased glucagon-like-peptide 1; (b) renal glycosuria; (c) defects in glucagon response; (d) high insulin sensitivity, probably the most frequent cause (50-70%), which is not adequately compensated by hypoinsulinemia and thus cannot be measured by indices of insulin sensitivity such as the homeostatic model assessment. Such situations are frequent in very lean people, or after massive weight reduction, or in women with moderate lower body overweight. PRH is influenced by patient's alimentary habits (high carbohydrate-low fat diet, alcohol intake). Thus, diet remains the main treatment, although alpha-glucosidase inhibitors and some other drugs may be helpful.

Blood Glucose↗

[Hemorheological aspects of leuko-platelet activation in atheromatous diseases: clinical applications].

Atherosclerosis (and its evolution towards thrombotic accidents) is now considered to be an inflammatory disease in which the interaction among endothelium, leukocytes and platelets plays a determining role. However, large scale epidemiological studies only indirectly reveal the leukocyte activation through somewhat simplistic markers, such as elastase or leukocyte counts. Interestingly, these markers seem to be independent predictors of ischemia distal to the atheromatous lesion. This leukocyte activation is usually associated with more classical hemorheological disturbances affecting blood viscosity and fibrinogen which, on multivariate analysis, also appear to be determinants of atheromatous lesions and their ischemic and thrombotic consequences, statistically independent of the "classical risk factors". Leukocyte activation probably plays an important role in these hemorheological disturbances, because it is associated with the production of leukocyte secretory products (proteolytic enzymes, free radicals, cytokines) which can alter the red cells and make them more aggregable and more rigid, and can increase the production of fibrinogen. These interactions remain incompletely understood, as illustrated by the still unclear role of NO which, depending on the experimental conditions, can have antiatherogenic or proatherogenic effects. The production by the leukocyte of substances leading to hyperviscosity is amplified by hypoxia, while the improvement in claudication distance resulting from walking exercise is associated with a joint fall of the "classical" factors of viscosity and of leukocyte activation markers. All this suggests that leukocyte activation and hyperviscosity are closely interdependent phenomena in the course of atheromatous disease and that, despite the complexity of these interactions, relatively simple and reasonably priced biological markers of this process will become available to the clinician.

Arterial Occlusive Diseases↗

Serum leptin is associated with the perception of palatability during a standardized high-carbohydrate breakfast test.

Leptin is an adipocyte-derived signalling molecule which plays a key role in the regulation of body weight and energy expenditure. Since its involvement in human eating behaviour is still poorly understood, we investigated whether the perception of palatability of food was related to fasting serum leptin levels. Twenty-six non-diabetic subjects, six men and twenty women of widely ranging age and body mass index, performed a standardized high-carbohydrate breakfast test. Palatability was evaluated with a visual analogue scale, body composition by bioelectrical impedance, serum leptin and plasma insulin by radioimmunoassay. Palatability was correlated to fasting serum leptin levels independently of body mass index, body fat mass and percentage of body fat (P<0.01). No significant relation was observed with peaks of insulinaemia, integrated concentrations of insulin or insulin resistance indices. A stepwise regression analysis indicated that serum leptin gave the strongest predictive association with palatability. These results suggest that the leptin system may be involved in the regulation of human eating behaviour in relation to the perception of palatability of food.

Adult↗