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Biomedical subjects

F Chevallier

Publications and source records attributed to F Chevallier.

At least 19 recordsLinked to original sources

Erythropoietin blood level is increased in sudden infant death.

Erythropoietin (EPO) is the main red cell growth factor and its release into the blood stream is stimulated by anemia and also by various kinds of hypoxia. We studied the blood EPO concentration in a population of 96 infants who died suddenly and compared their mean EPO levels to control infants. The normal values were low at birth and progressively increased during the first 2 years. In the sudden infant death (SID) group the EPO level was significantly higher (p = 0.001) for the entire population and particularly in the youngest group (0-2 months): 14.7 +/- 2.4 IU/l (mean +/- SEM) in SID group vs. 3.6 +/- 0.4 IU/l in control group (p < 0.001). Although we could not analyze the blood hemoglobin concentration after death, the anemia hypothesis was refuted by an assay of the percentage of fetal hemoglobin which was normal for age in the control and SID groups. Moreover, there was no significant difference in EPO levels between explained and unexplained deaths. We also observed an increase in the stress hormones, cortisol and beta-endorphin, in the entire SID group. These SID results suggest a profound and long-lasting hypoxia at least during terminal agony.

Adrenocorticotropic Hormone

[Contribution of molecular biology to the prevention of cystic fibrosis. Experience in Lyon].

Enzymatic prenatal diagnosis of cystic fibrosis was performed in 113 amniotic fluids and DNA polymorphism was studied in 104 families, including 28 cases with prenatal material analysis. According to the results, the enzymatic diagnosis should be cautiously interpreted when the risk is less than 1/4. In these situations DNA analysis in the parents is very helpful to assess the reliability of enzymatic diagnosis.

Amniotic Fluid

Origin and fate of cholesterol in rat plasma lipoproteins in vivo. I. Qualitative analysis.

Rats were conditioned to ingest a 15-gram dietary mixture, in a single daily meal, between 6:00 and 9:00 a.m. Labeled cholesterol was introduced into the organism through four different physiological routes: ingestion of 14C-cholesterol, injection of 14C-acetate, injection of red cells or plasma whose cholesterol was tritium-labeled. The specific radioactivities of free and esterified cholesterol, in the different plasma lipoproteins and in the major organs, were measured at various time spans after the introduction. The results revealed a different source of cholesterol in chylomicrons and VLDL discharged by the intestine: the chylomicrons would principally carry esterified cholesterol coming from the intestinal contents, while esterified cholesterol coming from the intestinal wall was found mainly in VLDL. The free cholesterol of these lipoproteins would initially have the same origin as esterified cholesterol but rapid free cholesterol exchanges would introduce precociously cholesterol coming from other structures. The results demonstrated the significant role of the intestine in cholesterol synthesis and revealed that of VLDL in the internal secretion of cholesterol by the intestine. Chylomicrons also appeared to play a significant role in this secretion, by way of exchanges between intestinal cells and chylomicrons in the process of formation. Finally, the results suggested the existence of esterified cholesterol transfers from HDL to lower density lipoproteins (chylomicrons, VLDL and possibly LDL).

Animals

Origin and fate of cholesterol in rat plasma lipoproteins in vivo. II. Modelling of cholesterol absorption and its release into plasma lipoproteins.

After a single ingestion of a diet containing 14C-cholesterol, cholesterol radioactivity in the stomachal and intestinal contents, in the different organs and in the very low density lipoproteins (VLDL) and chylomicrons was measured at different times during 2 days. Based on the results, a quantitative model of cholesterol absorption and of its release into the VLDL and chylomicrons has been elaborated. This model takes into account the different processes implied in the turnover of intestinal cholesterol and that of the entire organism. It constitutes a coherent whole (satisfactory simulations for the variables studied, suitable mass balances for each compartment and the absence of major contradictions with preexisting quantitative data). Once again the model demonstrates the important part played by the intestine in rat cholesterol system dynamics. It takes into account the existence of two related exogenous and endogenous cholesterol pools from which the cholesterol released by the intestine into the chylomicrons and VLDL originates. The results suggest the existence of an important esterified cholesterol uptake from other plasma lipoproteins by the chylomicrons.

Animals

Effect of portacaval or mesentericocaval anastomosis on cholesterol metabolism in rats.

Portacaval anastomosis (PCA) lowered by 50% the cholesterol concentration in the plasma of rats. The free and esterified cholesterol contents in the lipoproteins were decreased with the very low density lipoproteins most affected (-85%). Cholesterol concentration as total content in the liver was reduced. The major change in the cholesterol metabolism, as studied with an isotopic equilibrium method, was the decrease in the intestinal absorption coefficient of dietary cholesterol (56.0 +/- 2.7% instead of 73.3 +/- 1.9% in controls). The rate of cholesterol transformation into bile acids was decreased (10.5 +/- 0.3 vs 14.5 +/- 0.5 mg/day/rat in controls). The rate of internal secretion of cholesterol was slightly reduced while the rate of fecal external secretion was increased, suggesting that the synthesis of cholesterol by extra-digestive tissues (including liver) was reduced after PCA. The effects of PCA on cholesterol metabolism were similar to those described for glucagon administration. Since this shunt results in hyperglucagonemia, it is suggested that this hormonal perturbation was the main factor involved in the modifications of cholesterol metabolism after PCA. Moreover, mesentericocaval anastomosis, which shunts only the intestinal blood and allows the pancreatic hormones a normal transport through the liver, did not significantly modify cholesterol metabolism. Only cholesterolemia (-28%) and the absorption coefficient of dietary cholesterol (66.0 +/- 2.3%) were slightly reduced.

Animals

[Effect of short- or medium-chain fatty acids on cholesterol dynamics in the rat].

The effects of a diet consisting of 10% medium-chain triglycerides (C8:0, C10:0) or 10% homogeneous triglycerides of 6- to 14-carbon chain saturated fatty acids on cholesterol turnover processes were studied in rats using the isotope equilibrium method. Cholesterol absorption was not significantly affected by the type of dietary fatty acid ingested. In contrast, lengthening of the fatty acid chain caused a moderate increase in the rates of cholesterol secretion (internal and external) and of transformation into bile acids. Thus, cholesterol synthesis was 80% higher in rats fed trimyristin (25.7 mg/day) than in those receiving tricaproin (14.6 mg/day). This increase seems essentially due to stimulated liver cholesterogenesis, as shown by in vivo incorporation of 14C-acetate.

Animals

Comparative methods of quantifying fecal neutral sterols in rats and humans after intravenous [14C]-, [3H] or [2H]cholesterol labeling.

Several methods used to estimate the fecal elimination of neutral sterols and of cholesterol having a plasmatic origin (called 'excreted cholesterol') were compared in rats and humans according to the tracer intravenously administered: 14-14C], [1,2-3H]- or octadeuterated cholesterol. In both species, octadeuterated cholesterol had no isotopic effect and the chance occurrence of epicoprostanol in fecal sterols induced an error in the calculation of the fecal excretion of cholesterol. In humans, the use of [1,2-3H]cholesterol appeared to be inaccurate in measuring the fecal flows of cholesterol, because of a loss of 3H radioactivity during the bacterial transformation of cholesterol in the digestive tract. Consequently, the reference method needed to calculate the proportion of excreted cholesterol in fecal cholesterol consisted in dividing the isotopic concentration measured in purified fecal cholesterol by that measured in the appropriate plasma cholesterol sample.

Animals

[Cholesterolemia and pyrexy (author's transl)].

During pyretic diseases from any origin, total plasma cholesterol level decreases and its values are frequently below 1 g per liter. This observation could be expected because it conforms with the following theory : 1) cholesterol synthesis in an organism is proportional to consumed energy, 2) plasma cholesterol level is the lower as cholesterol synthesis is high.

Adult

In vivo study of cholesterol turnover in tissues of adult sows.

The in vivo study of free and esterified cholesterol turnover was carried out in 15 tissues of adult Large White sows maintained at a constant weight for 10-12 weeks. They received a single intravenous injection either of [1-14C] acetate, or of an autologous red cell suspension or of plasma, previously labelled in vitro (for red cells) or in vivo (for plasma) with tritiated cholesterol. The tissues can be separated into four groups according to their relative rate of free cholesterol exchange between plasma and tissues. The liver and the lungs have a very fast exchange rate whereas the brain and the spinal cord have a very slow one. The whole lipoprotein particle transfer--an exclusive model for the esterified cholesterol transport from plasma to tissues--has been found in all sow tissues. When [1-14C] acetate is used as a substrate for cholesterol synthesis, lungs, adrenal glands and heart do not seem--or at an extremely low rate--to convert acetate into cholesterol whereas an intense cholesterol synthesis takes place in the small intestine. Its contribution to cholesterol synthesis in sows--taking into account the cholesterol transfer processes--reaches 70 per cent.

Animals

Cholesterol turnover in human plasma lipoproteins: studies with stable and radioactive isotopes.

The kinetics of cholesterol labeling was studied in the plasma lipoproteins of three subjects who had received an oral dose of octadeuterated cholesterol and an intravenous administration of 3H-cholesterol and 14C-mevalonate or 13C-acetate. After each labeled cholesterol pulse into the plasma (absorption, exchange, or synthesis), the isotopic concentrations of free and esterified cholesterol became identical after 120 h. Before this time, very low-density lipoprotein free cholesterol appeared more easily exchangeable than high-density and low-density lipoprotein free cholesterol, high-density lipoproteins were shown to be a source for very low-density lipoprotein cholesterol esters and the role of very low-density lipoproteins associated with chylomicrons was demonstrated in the initial transport of dietary cholesterol. The rates of the various processes involved in cholesterol turnover were calculated. The total cholesterol inflow into the plasma by absorption and synthesis, determined by long-term kinetic data (18 or 28 wk) was consistent with the result obtained by sterol balance for the total cholesterol outflow from the plasma (fecal excretion and conversion into bile acids).

Adult

Origins of neutral sterols in human feces studied by stable isotope labeling (D and 13C). Effect of phytosterols and calcium.

A stable isotope labeling (13C and D) was administered to 8 subjects in order to observe the short-term effect of phytosterols (Cytellin 9 g/day) or calcium (calcium gluconate 3 g/day) on the processes involved in cholesterol elimination in the feces. Under control conditions, the mean fraction of fecal cholesterol having a plasmatic origin was 69% and that of cholesterol secreted by the digestive tract 11%. The remaining fraction represented unabsorbed dietary cholesterol. While both treatments reduced the absorption of cholesterol, Cytellin enhanced the fecal excretion of plasma cholesterol and calcium lowered it. The change observed in the rate of intestinal external secretion did not follow the change in the fecal excretion of cholesterol.

Adult

Modes of intestinal cholesterol absorption in adult sows.

The nature and distribution of neutral sterols has been determined in the digestive tract of adult Large White sows maintained in a defined biological steady state (constant weight: 70 +/- 5 kg). The semi-synthetic diet contained 0.08 p. 100 cholesterol. Cholesterol was the main sterol of the intestinal contents. From the caecum, it was partially transformed into coprostanol (less than 6 p. 100). Just before the morning meal, the intestinal contents of the sows were rich in cholesterol (532 mg in the small intestine). As in rats, this rapidly renewed cholesterol of endogenous origin was not distributed homogeneously with the exogenous dietary cholesterol. During intestinal cholesterol transit, hydrolysis exceeded esterification. Using the principle of occupancy of every dynamic system, two isotopes were employed to measure the absorption coefficient: cholesterol-4-14C (10 microCi), incorporated into the meal and ingested at one time, and cholesterol-3H (400 microCi), injected intravenously once in a suspension of autologous red blood cells previously labelled in vitro. The absorption coefficient of dietary cholesterol in our experimental conditions reached 57 +/- 4 p. 100. The cholesterol was mainly absorbed in the first-half of the small intestine as in man, whereas in rat it is absorbed in the second-half. This dietary tracer appeared in the general circulation later in swine than in rat or man. After intake of a meal containing the cholesterol tracer, maximal plasma cholesterol radioactivity was reached after 48 hrs in the sows while it is reached after 10-12 hrs in rat or man.

Animals

Identification and origins of neutral fecal sterols in adult Large White sows: occurrence of externally-secreted intestinal cholesterol.

Cholesterol, the main neutral fecal sterol (54-84 p. 100) in adult Large White sows fed a controlled semi-purified diet containing 0.08 p. 100 cholesterol (500 g twice a day; 3 510 kcal/day), was partially converted into coprostanol (10-44 p. 100). Exceptionally, epicoprostanol was present, indicating a second pathway of bacterial cholesterol degradation. In this paper, the term "fecal cholesterol" is restricted to the sum of cholesterol + coprostanol. The contribution of fecal cholesterol to the bulk of neutral fecal sterols eliminated daily, averaged 97 +/- 1 p. 100. For a given dietary cholesterol intake of 80 mg per day, eliminated fecal cholesterol was estimated to be 392 +/- 47 mg/day and mean fecal cholesterol concentration 1.88 +/- 0.12 mg/g of stools. The various sources of fecal cholesterol were unabsorbed ingested cholesterol, cholesterol excreted from the plasma, and externally-secreted intestinal cholesterol, synthesized by the digestive tract, discharged into the lumen and not absorbed. The respective contributions of these different sources were as follows: unabsorbed dietary cholesterol 34 +/- 2 mg/day, excreted cholesterol 234 +/- 28 mg/day and externally-secreted cholesterol 125 +/- 23 mg/day.

Animals

Origins of neutral sterols in human feces studied by stable isotope labeling (D and 13C). Existence of an external secretion of cholesterol.

An experimental procedure using stable isotope-labeled cholesterol (13C and D) was carried out on 15 healthy subjects to distinguish the different origins of neutral fecal sterols in man: nonabsorption of dietary cholesterol, fecal excretion by transfer of plasmatic cholesterol and external secretion of cholesterol biosynthetized in digestive tract and directly eliminated. For a mean daily mass of 652 mg of fecal cholesterol, unabsorbed dietary cholesterol is 20% (133 mg), excreted cholesterol 67% (434 mg) and cholesterol from external secretion 13% (85 mg). A short treatment (4 days) with cholestyramine or different bile acids was then administered to each subject to study the possible variations in their fecal elimination of cholesterol. The more evident effect was the large stimulation of external secretion of cholesterol (234 mg/day) observed after chenodeoxycholic acid feeding (1 g/day). This treatment tends also to decrease dietary cholesterol absorption and to enhance excretion of cholesterol.

Adult

[Cholesterolemia and pyrexy (author's transl)].

During pyretic diseases from any origin, total plasma cholesterol level decreases and its values are frequently below 1 g per liter. This observation could be expected because it conforms with the following theory: 1) cholesterol synthesis in an organism is proportional to consumed energy, 2) plasma cholesterol level is lower as cholesterol synthesis is high.

Adult

Fluctuations in blood cholesterol level: a rational analysis.

Laws governing rat and human blood cholesterol levels have been previously described. These laws reveal that cholesterol in the plasma constitutes an open non-linear system. In this hypothesis, the present paper attempts to explain the variations of cholesterolemia. As in every dynamic system, fluctuations can be observed after changes either in the orders of the system (inputs), or in the values of the parameters. The response of the system (cholesterolemia fluctuations) is analyzed in these various circumstances.

Animals