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Biomedical subjects

M Clément

Publications and source records attributed to M Clément.

14 recordsLinked to original sources

Alteration of delta-6 desaturase by vitamin E in rat brain and liver.

delta-6 Desaturase, measured at substrate saturation using linoleic acid, was found to be increased by more than two-fold when the content of vitamin E in brain microsomal membrane suspension was increased (up to 7.5 micrograms/mg membrane protein, i.e. 100 micrograms/g tissue from which microsomes were prepared). In contrast, this activity was reduced by 25% in the liver. This raises the question of the multiple role of vitamin E in membranes, the control of membrane polyunsaturated fatty acids through synthesis, and their protection against peroxidation.

Animals

Structural and functional importance of dietary polyunsaturated fatty acids in the nervous system.

The nervous system is the organ with the second greatest concentration of lipids. These lipids participate directly in membrane functioning. Brain development is genetically programmed. It is therefore necessary to ensure that nerve cells receive an adequate supply of nutrients, especially of lipids, during their differentiation and multiplication, and throughout their lives. The effects of polyunsaturated fatty acid deficiency have been extensively studied; prolonged deficiency leads to death in animals. Linoleic acid is now universally recognized to be an essential nutrient. Until recently, however, alpha-linolenic acid was considered non-essential. Feeding animals with oils that have a low alpha-linolenic content results in all brain cells and organelles and various organs having reduced amounts of 22:6n-3, which is compensated for by an increase in 22:5n-6. The speed of recuperation from these anomalies is extremely slow for brain cells, organelles, and microvessels, in contrast to other organs. A decrease in alpha-linolenic series acids in the membranes results in a 40% reduction in the Na(+)-K(+)-ATPase of nerve terminals and a 20% reduction in 5'-nucleotidase. Some other enzymatic activities are not affected, although membrane fluidity is altered. A diet low in alpha-linolenic acid induces alterations in the electroretinogram which disappear with age; motor function and activity are little affected, but learning behavior is markedly altered. The presence of alpha-linolenic acid in the diet confers a greater resistance to certain neurotoxic agents (triethyl-lead). During the period of cerebral development, there is a linear relationship between brain content of n-3 acids and the n-3 content of the diet up to the point where alpha-linolenic levels reach 200 mg for 100 g of food intake. Beyond that level there is a plateau. For other organs, such as the liver, the relationship is also linear up to 200 mg/100 g, but then there is merely an abrupt change in slope and not a plateau. When dietary 18:2n-6 content was varied, it was noted that 20:4n-6 optimum values were obtained at 150 mg/100 g for all nerve structures, 300 mg for testicle and muscle, 800 mg for kidney, and 1200 mg for liver, lung and heart. A deficiency in alpha-linolenic acid and an excess of linoleic acid have the same main effect: an increase in 22:5n-6 levels.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals

Age-related changes in antioxidant enzymes and lipid peroxidation in brains of control and transgenic mice overexpressing copper-zinc superoxide dismutase.

The aim of our study was first to obtain a comprehensive profile of the brain antioxidant defense potential and peroxidative damage during aging. We investigated copper-zinc superoxide dismutase (CuZnSOD), manganese superoxide dismutase (MnSOD), seleno-dependent glutathione peroxidase (GSH-PX), glutathione reductase (GSSG-R) activities, endogenous and in vitro stimulated lipid peroxidation in 40 brains of control mice divided into 3 age groups: 2 months (young), 12 months (middle-aged) and 28 months (old). We found a positive correlation between age and activities of CuZnSOD (r = 0.47; P < 0.01) and GSH-PX (r = 0.72; P < 0.0001). CuZnSOD and GSH-PX activities are independently regulated during brain aging since temporal changes of these two enzymes do not correlate. No modification in MnSOD activity and basal lipid peroxidation was observed as a function of age. Nevertheless, stimulated lipid peroxidation was significantly higher at 12 months (6.53 +/- 0.71 mumole MDA/g tissue) than at 2 months (5.69 +/- 0.90) and significantly lower at 28 months (5.13 +/- 0.33) than at 12 months. Second, we used genetic manipulations to construct transgenic mice that specifically overexpress CuZnSOD to understand the role of CuZnSOD in neuronal aging. The human CuZnSOD transgene expression was stable during aging. The increased CuZnSOD activity in the brain (1.9-fold) of transgenic mice resulted in an enhanced rate of basal lipid peroxidation and in increased MnSOD activity in the 3 age groups. Other antioxidant enzymes did not exhibit modifications indicating the independence of the regulation between CuZnSOD and glutathione-related enzymes probably due to their different cellular localization in the brain.

Aging

T3 plus high doses of beta-blockers: effects on energy intake, body composition, bat and heart in rats.

The effects of a combined treatment with supraphysiological doses of the thyroid hormone T3 (15 micrograms/kg BW/day, s.c.) and high doses of a predominant beta 1-blocker (atenolol, 12.5 and 25 mg/kg BW, 3X/day, s.c.) or a non-specific beta-blocker (propranolol, 5 mg/kg BW s.c. and 33 mg/kg BW p.o., each 3X/day) on energy intake, body composition and the heart were studied in overfed rats with an increased body fat content. The goal of the study was to investigate whether the above treatment constitutes a therapy for obesity in that T3 causes weight and fat loss and the beta-blockers prevent the unwanted T3-effects on the heart (tachycardia and increased heart weight). T3 did not increase energy intake above the level seen in overfed animals. It caused loss of body weight due to loss of fat but not protein, an increase in interscapular brown adipose tissue (IBAT) weight and fat, tachycardia and an increase in heart weight. Atenolol and propranolol blocked T3-induced tachycardia. With the exception of the highest propranolol dose which abolished the T3-induced increase in IBAT fat content, the beta-blockers did not modify the other T3 effects. Thus, in spite of the weight and fat loss and the lack of significant protein loss and tachycardia observed under T3/high dose beta-blockers treatment, the T3-induced increase in heart weight makes this treatment unsuitable as a therapy for obesity.

Adipose Tissue

Comparative effects of ethanol, n-propranol and isopropanol on lipid disposal by rat liver.

Besides ethanol, other aliphatic alcohols such as n-propanol and isopropanol induce a triacylglycerol (TAG) accumulation in the liver. To determine whether a common mechanism is responsible for the effects of these three alcohols on hepatic lipid metabolism, each was administered by gastric tube to female Wistar rats at the dose of 50 mmol/kg body wt. Whichever alcohol was administered, the hepatic triacylglycerol accumulation was found to be related to the duration of elevated blood alcohol concentration. After administration of n-propanol or isopropanol, the liver [14C]palmitate uptake was increased whereas hepatic palmitate oxidation to 14CO2 was impaired and palmitate esterification into TAG enhanced; these perturbations were however more discrete than after ethanol administration. In contrast to ethanol and n-propanol which, at the dose presently used, increase precursor incorporation into blood TAG, isopropanol inhibits this incorporation. Interference with the process of very low density lipoprotein (VLDL) synthesis and/or secretion, which appears only at a late stage of isopropanol intoxication, is probably responsible for the intensity and duration of the fatty liver observed after administration of this alcohol.

1-Propanol

[Bone lesions in a case of heavy chain alpha disease (author's transl)].

Specific bone lesions are not usually found in heavy chain alpha disease we report a case in which images identical to those seen in Parker and Jackson's sarcoma (bone lymphoma) were found. The malignant lymphomatous nature of the lesion could not be confirmed as a bone biopsy was not made, but its regression under chemotherapy makes the diagnosis almost certain. Indirectly, arguments in favour of this hypothesis can be drawn from the common cellular origin of bone lymphomas and monoclonal gammopathies. Furthermore, it is logical to assume that heavy chain alpha disease, as with most other immuno-proliferative syndromes, can be associated with malignant lymphomatous changes in the skeleton.

Adult

[Comparison of the effect of acetone and isopropanol on lipid metabolism in rats].

Isopropanol and acetone administered to rats in conditions leading to a similar blood acetone level differ markedly in their effects on lipid metabolism. Isopropanol administration determines a fatty liver, which is mainly related to a defect in hepatic lipoprotein synthesis. Acetone administration gives only raise to a slight increase in the liver triacylglycerol level. It does not alter the [1-14C] palmitate, [1-14C] glycerol or [U-14C] leucine incorporation into blood lipoproteins. Acetone does thus not appear to play a preminent role in the isopropanol induced fatty liver which seems to be related mainly to a direct action of the alcohol itself.

1-Propanol

[The possible protective effect of cysteine during acute alcohol intoxication].

In the experimental conditions used, cysteine administered per os together with ethanol reduces the blood alcohol levels, but does not modify significantly the rate of alcohol oxidation. No effect of cysteine administration is however observed when ethanol is injected intraperitoneally. Cysteine addition in vitro enhances ethanol consumption by liver slices and reduces at the same time 14CO2 production from [2-14C] ethanol. This effect is only observed with a high cysteine/ethanol molar ratio. The changes in the blood alcohol level resulting from cysteine administration do not appear to result from such an interaction with ethanol oxidation, but seem to be due to a delayed ethanol absorption from the gastrointestinal tract.

Administration, Oral

Effect of pyrazole administration on the isopropanol induced fatty liver.

The isopropanol induced fatty liver is prevented in the rat by prior administration of pyrazole. Acetone administration, on the other hand, determines an increase in the hepatic triglyceride level. These results suggest the implications of acetone in the induction of the fatty liver following acute isopropanol administration in the rat.

1-Propanol

[Action of isopropanol on rat lipid metabolism: complementary studies on mechanisms implicated in hepatic accumulation of triacylglycerides].

Isopropanol administration (3 g/kg, p.o.) determines in the rat liver an inhibition of fatty acid oxidation, an enhancement of fatty acid esterification into triacylglycerols as well as an inhibition of lipoprotein secretion which appears to be related to alterations in hepatic phospholipids and which differentiates isopropanol from ethanol induced fatty liver. Disturbances in peripheral lipolysis following isopropanol administration are found only in mature rats and are not necessary to the fatty liver induction.

1-Propanol

[Study of interventricular septal defects with equal aortic and pulmonary artery pressures. Classification by clinical and computer methods of 70 cases].

Application of various methods of classification to a group of 70 cases of ventricular septal defect with high pulmonary artery hypertension allowed a comparative study between the various methods aiming at distinguishing the forms with low from high pulmonary artery resistance. The reference clinical classification provides supplementary informations derived from the natural or post-operative course and eventually from the microscopic examination. The first automatic classification relies on the study of a single criterion: the pulmonary arteriolar resistance and the systemic resistance ratio. A second classification is based on the attribution of points to some clinical or haemodynamic signs resulting in a score orienting the classification of every individual. Multifactorial analysis methods deal with all the available informations for the overall group, and suppose the use of a computer. The informatic methods make it possible to study the classifying value of every sign. Correlations were established between these various techniques and the medical classification.

Adolescent

Prone immersion physical exercise therapy in three children with cystic fibrosis: a pilot study.

Prone immersion physical exercise therapy has been used successfully in the physical rehabilitation of middle-aged adults with moderate to severe chronic obstructive pulmonary disease. The purpose of this pilot project was to evaluate the effects of PIPE therapy in children with cystic fibrosis. Three children with CF, two boys aged 6 and 14 years and one girl aged 15 years, voluntarily participated in the experimental training program. The patients performed individualized group exercise three times a week on alternate days for 28 consecutive weeks at an intensity of approximately 75 percent aerobic capacity. Duration of exercise gradually increased from 15 (3 x 5 minutes) to 60 (3 x 20 minutes) minutes while the rest period after each exercise was constant at two minutes. PIPE training resulted in increased physical work capacity and maximal oxygen consumption in all three subjects. Curiously, these changes were not accompanied by training bradycardia.

Adolescent