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Biomedical subjects

P Pittet

Publications and source records attributed to P Pittet.

16 recordsLinked to original sources

Myofibroblast development is characterized by specific cell-cell adherens junctions.

Myofibroblasts of wound granulation tissue, in contrast to dermal fibroblasts, join stress fibers at sites of cadherin-type intercellular adherens junctions (AJs). However, the function of myofibroblast AJs, their molecular composition, and the mechanisms of their formation are largely unknown. We demonstrate that fibroblasts change cadherin expression from N-cadherin in early wounds to OB-cadherin in contractile wounds, populated with alpha-smooth muscle actin (alpha-SMA)-positive myofibroblasts. A similar shift occurs during myofibroblast differentiation in culture and seems to be responsible for the homotypic segregation of alpha-SMA-positive and -negative fibroblasts in suspension. AJs of plated myofibroblasts are reinforced by alpha-SMA-mediated contractile activity, resulting in high mechanical resistance as demonstrated by subjecting cell pairs to hydrodynamic forces in a flow chamber. A peptide that inhibits alpha-SMA-mediated contractile force causes the reorganization of large stripe-like AJs to belt-like contacts as shown for enhanced green fluorescent protein-alpha-catenin-transfected cells and is associated with a reduced mechanical resistance. Anti-OB-cadherin but not anti-N-cadherin peptides reduce the contraction of myofibroblast-populated collagen gels, suggesting that AJs are instrumental for myofibroblast contractile activity.

Actins↗

Metabolic effects of a mixed and a high-carbohydrate low-fat diet in man, measured over 24 h in a respiration chamber.

1. The relation between dietary carbohydrate: lipid ratio and the fuel mixture oxidized during 24 h was investigated in eleven healthy volunteers (six females, and five males) in a respiration chamber. Values of the fuel mixture oxidized were estimated by continuous indirect calorimetry and urinary nitrogen measurements. 2. The subjects, were first given a mixed diet for 7 d and spent the last 24 h of the 7 d period in a respiration chamber for continuous gas-exchange measurement. The fuels oxidized during 2.5 h or moderate exercise were also measured in the respiration chamber. After an interval of 2 weeks from the end of the mixed-diet period, the same subjects were given an isoenergetic high-carbohydrate low-fat diet for 7 d, and the same experimental regimen was repeated. 3. Dietary composition markedly influenced the fuel mixture oxidized during 24 h and this effect was still present 12 h after the last meal in the postabsorptive state. However, the diets had no influence on the substrates oxidized above resting levels during exercise. With both diets, the 24 h energy balance was slightly negative and the energy deficit was covered by lipid oxidation. 4. With the high-carbohydrate low-fat diet, the energy expenditure during sleep was found to be higher than that with the mixed diet. 5. It is concluded that: (a) the composition of the diet did not influence the fuel mixture utilized for moderate exercise, (b) the energy deficit calculated for a 24 h period was compensated by lipid oxidation irrespective of the carbohydrate content of the diet, (c) energy expenditure during sleep was found to be higher with the high-carbohydrate low-fat diet than with the mixed diet.

Adult↗

Caffeine and coffee: their influence on metabolic rate and substrate utilization in normal weight and obese individuals.

A series of four trials was carried out to investigate the effects of caffeine and coffee on the metabolic rate and substrate utilization in normal weight and obese individuals. In the first trial 8 mg/kg caffeine was compared with a placebo in normal weight subjects. Metabolic rate increased significantly during the 3 hr after caffeine ingestion. While plasma glucose, insulin, and carbohydrate oxidation did not change significantly, plasma free fatty acid levels rose from 432 +/- 31 to 848 +/- 135 muEq/liter and were accompanied by significant increases in fat oxidation during the last hour of the test. In the second and third trials the effects of coffee providing 4 mg/kg caffeine were studied in control and obese subjects. Metabolic rate increased significantly in both groups; however, significant increases in fat oxidation were only observed in the control group. Plasma free fatty acids did not change in the obese. In the fourth trial, coffee was taken with a 3080 kJ meal. The thermic effect of the meal was significantly greater after coffee than after decaffeinated coffee and again fat oxidation was significantly greater after coffee. In conclusion caffeine/coffee stimulates the metabolic rate in both control and obese individuals; however, this is accompanied by greater oxidation of fat in normal weight subjects.

Adult↗

A new method for measuring the body density of obese adults.

1. A new apparatus is described with which it is possible to measure the volume (and hence density) of obese patients without requiring them to immerse totally in water. Replicate measurements of subjects with 6, 23 and 38 kg body fat had a standard deviation not greater than 0.3 kg fat. 2. In nineteen obese women body fat was measured by density, total body water, and total body potassium at the beginning, and again at the end, of a period of 3--4 weeks on a reducing diet, during which they lost 5.43 (SD 1.83) kg in weight. The composition of weight loss was also estimated both by energy balance and nitrogen balance during the interval between the two measurements of body composition. 3. The estimates of fat content of the ninetten women at the start of the balance period were 45.63 (SD 14.50) kg by density, 48.07 (SD 13.88) kg by K and 47.09 (SD 13.85) kg by water. The correlation coefficient between the density and K estimate was 0.949, and for the density and water estimate it was 0.971. 4. It is concluded that measurement of density by the new method provides a convenient method for estimating body fatness, and change in fat content, which compares favourably with estimates based on total body water or total body K. However, these methods cannot be used to provide an accurate estimate of the composition of a small weight loss in an individual since deviations up to 4 kg fat occur between fat loss based on change in density and those based on the more reliable (but more tedious) energy balance method.

Adipose Tissue↗

Thermic effect of glucose in obese subjects studied by direct and indirect calorimetry.

1. The thermic effect of a glucose load (50 g) was studied in ten control and eleven obese female subjects, using both direct and indirect calorimetry simultaneously. Experiments were done under conditions of thermal equilbrium (28 degrees and 30% relative humidity). 2. Thermal balance (heat production measured by indirect calorimetry minus heat losses measured directly) was negative in the control group during the fasting period (heat deficit -14-2 +/- 5-0 kJ/m2 per h), whereas that of the obese group was in equilibrium (+ 1-4 +/- 4-8 kJ/m2 per h). 3. After the glucose load, metabolic rate increased 13-0 +/- 1-5 and 1-3% in the control and obese groups respectively. 4. In contrast to the metabolic rate, total heat losses were not significantly altered in either group after the glucose load. Total heat losses of the obese group were significantly lower than those of the control group throughout the experimental period. 5. During the experiments the amount of heat stored was increased in both groups. Thermal balance in the control group became positive while that of the obese group remained positive. 6. During the fasting period, the control subjects oxidized more carbohydrates (90-4 mg/min) than lipids (68-8 mg/min), whereas obese subjects oxidized more lipids (103-7 mg/min) than carbohydrates (50.2 mg/min). After the glucose load, the oxidation rate of carbohydrates was increased in both groups to 158-1 mg/min in control subjects and 95-6 mg/min in obese subjects. 7. The mean skin temperature of the control subjects was significantly higher than that of the obese subjects and remained higher throughout the postprandial period. 8. These results indicate that: (a) during the fasting period, the energy sources utilized and the thermal balance of the two groups were different; (b) the thermic effect of glucose was less in the obese subjects and, therefore, might be a factor contributing to their low energy expenditure.

Adult↗

Heat storage regulation in exercise during thermal transients.

Rate of heat storage (S) was measured by using direct and indirect calorimetry simultaneously in 11 subjects during rest and exercise at three ambient temperatures (Ta of 20, 25, and 30 degrees C), and at two work intensities (40 and 90 W). At rest, the mean value of S was -64.9 W at 20 degrees C, -26.1 W at 25 degrees C, and +9.9 W at 30 degrees C. After 50 min of exercise at 40 or 90 W, S tended toward zero at the three ambient temperatures. This indicates that thermal equilibrium was reached. In addition, at the end of the exercise periods total heat losses (R + C + E) measured at a Ta of 20, 25, and 30 degrees C were similar, i.e., independent of Ta. During the thermal transients and the steady state of exercise, the calorimetric method allows immediate measurement of S to be made, since all the physical terms of the body heat balance equation are determined. The changes in mean body temperature (delta Tb) measured by thermometry showed a delay of 5-10 min when compared with delta Tb measured by calorimetry. Thus, determination of delta Tb by thermometry is not directly applicable during thermal transients, unless the observed delay is taken into account. Our results also support the concept that Tb may be the regulated variable of the thermoregulatory system, since we obtained a very significant and uniform correlation between Esk and delta Tb at the three Ta and the two work intensities which were studied.

Adult↗

[Heat debt and thermal insulation in women exposed to cold : contribution of direct calorimetry to the study of a mathematical model (author's transl)].

1. Measurements of total heat losses by direct calorimetry, metabolic heat production by indirect calorimetry, body temperatures by thermometry, and thickness of subcutaneous fat with skin-fold calipers were made in four groups of subjects (anorexic, controls, trend to obesity, and obesity) at ambient temperatures of 28 degrees C and 20 degrees C. 2. At 28 degrees C, the four groups of subjects reached thermal equilibrium after 30 min. 3. Both metabolic heat production and total heat losses were lower in the anorexic group than in the control group. 4. Body thermal insulation was not simply related to the thickness of subcutaneous fat (passive insulation), but was actively regulated in such a way that thermal balance was attained by all subjects at 28 degrees C. Body tissues underlying the subcutaneous fat contributed to the thermal insulation of the subjects at both 28 degrees C and 20 degrees C. 5. At 28 degrees C, total body thermal insulation was higher in anorexic subjects than in controls. 6. At 20 degrees C, heat debt was similar in three of the four groups : the anorexic subjects showed a higher debt. 7. A highly significant correlation between subcutaneous fat and weight/area ratio, was found. 8. The heat exchange coefficient of radiation and convection was found to be 6,47 Wm-2 degrees C-1. 9. By combining our measured values with those of various tissue physical characteristics, it was possible to produce a mathematical model. With this model one can calculate the penetration of the thermal gradient into the body, and estimate the mean temperature of each tissue participating in the thermal insulation for moderately cold ambient temperatures.

Adolescent↗

[Measurement of carbohydrate oxidation by means of indirect continuous calorimetry in normal and diabetic subjects].

The use of continuous indirect calorimetry in the course of a 100 g OGTT in 10 normal subjects has shown that carbohydrate oxidation rises with the secondary fall in blood glucose, suggesting that it could result from glucose stored under the influence of insulin. The experimental increase in FFA by a neutral fat infusion in 8 normal subjects decreased this oxidation in spite of the insulin rise. In a group of 5 non-obese, non-ketotic insulin-deficient diabetics, carbohydrate oxidation was found to be normal and directly correlated with plasma glucose levels. On the other hand, in 7 obese diabetics with high plasma insulin levels carbohydrate oxidation was found to be low, suggesting that carbohydrate intolerance could result from the non-oxidation of glucose. This study shows heterogeneity of diabetes, since glucose intolerance could result from non-oxidation of glucose as well as from insufficient pancreatic secretion.

Administration, Oral↗

Interactions of insulin and epinephrine in human metabolism: their influence on carbohydrate and lipid oxidation rate.

Two groups of normal male subjects were given an infusion of insulin and an infusion of epinephrine + insulin respectively. Blood glucose, plasma free fatty acids (FFA), insulin, growth hormone, cortisol, and urinary catecholamines were determined. Continuous indirect calorimetry was used to measure metabolic rate and oxidation rates of carbohydrate and lipids. The first group (n equals 7) received a 30-minute insulin infusion (0.1 IU/kg). While blood glucose and plasma FFA decreased, carbohydrate oxidation and metabolic rate significantly increased after some delay, whereas lipid oxidation decreased. The increase in carbohydrate oxidation amounted to 5 g/120 min. The decrease in blood glucose during insulin administration did not correlate with the increase in carbohydrate oxidation. In the second group (n equals 7), a 150-minute epinephrine infusion (900 mug in 500 ml saline) was administered, and superimposed upon it, a similar insulin infusion initiated after 60 min. Epinephrine alone increased blood glucose and plasma FFA levels, and decreased insulinemia. The rise in the metabolic rate was sharp and significant. After a short but significant increase the oxidation rate of carbohydrate decreased, whereas that of lipids markedly rose. This increase significantly correlated with that in FFA. Addition of insulin markedly decreased the elevated FFA levels and lowered blood glucose. After some delay this was followed by a marked increase in carbohydrate oxidation and a decrease in lipid oxidation. In this test the total increase in carbohydrate oxidation was 11 g/120 min. In comparison with the insulin test, this double amount seems to correlate well with the higher blood glucose levels measured before insulin administration. The results suggest that insulin indirectly stimulates carbohydrate oxidation by facilitating glucose transport into the cells and lowering FFA levels, and that epinephrine favours lipid oxidation through its lipolytic effects and its suppression of insulin release.

Adult↗