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Biomedical subjects

R Michel

Publications and source records attributed to R Michel.

At least 109 records · Page 6Linked to original sources

Effects of short- and long-term thyroidectomy on mitochondrial and nuclear activity in adult rat brain.

We compared subcellular activities in brain and liver at various times after thyroidectomy. Male S.D. rats were used on days 5, 10 or 60 after surgery. Mitochondrial properties were estimated by determining the respective activities of oxidative phosphorylation, succinate oxidase, succinate and beta-hydroxybutyrate cytochrome c reductase and alpha-glycerophosphate dehydrogenase. Nuclear activity was estimated by measuring the RNA polymerase I activity. In brain, RNA polymerase I activity already declined at 5 days after thyroidectomy, whereas mitochondrial respiratory enzymes decreased significantly only after 60 days. In liver, nuclear RNA polymerase I and mitochondrial enzyme activities were observed to drop simultaneously by the 5th day after thyroid removal. On the other hand, daily T3 s.c. injections, 0.25 microgram/100 g B.W., were given for 10 days to rats immediately after thyroidectomy (10 days Tx) or to chronically hypothyroid rats (60 days Hth). Hormonal treatment either maintained or restored subcellular activities to their normal level, both in brain and liver. These data suggest that the metabolic properties of brain mitochondria are sensitive to thyroid hormones, but that the brain needs less iodothyronines than other organs. The fast reduction of RNA polymerase I by thyroidectomy and its subsequent restoration by T3 suggest that the nuclear activity greatly depends on thyroid status.

Animals↗

Thyroid status in the obese syndrome of rats.

The thyroid function was explored by comparing serum total and free iodothyronine levels in young male genetically obese Zucker rats and in their lean littermates, aged from 6 to 8 weeks old. Total and free thyroxine (T4) and 3,5,3'triiodothyronine (T3) levels were significantly decreased in obese rat serum while total 3,3',5'-triiodothyronine (rT3) remained constant. Radioactive T4 half life is slower in the plasma of obese rats. Peripheral synthesis of T3 from deiodination of T4 is also decreased in obese rat liver homogenate. These modifications produce changes in liver mitochondria oxidative phosphorylation and in marker enzyme activity, which are usually associated with hypothyroidism and hypothalamic disturbances. Genetic obesity probably involves activation of peripheral deiodination of T4 to rT3 which induces biochemical and metabolic changes.

Animals↗

[Metabolic effects of 3,5-dimethyl-3'-isopropyl-L-thyronine (DIMIT) in constant infusion by osmotic minipump to hypothyroid rat (author's transl)].

Our experiments show that the T3 nonhalogenated analog 3,5-dimethyl-3'-isopropyl-L-thyronine (DIMIT) exhibits the general activities of thyroid hormones. DIMIT delivered to hypothyroid Rat by constant infusion or sc injections increases bodyweight gain, BMR before or after epinephrine and phosphorylative oxidation of liver mitochondria.

Animals↗

Effect of thyroidectomy on pregnenolone and progesterone biosynthesis in rat adrenal cortex.

The effects of thyroidectomy on pregnenolone and progesterone biosynthesis were investigated in rat adrenal cortex mitochondria and microsomes. The sequential hydroxylations of cholesterol, and the latter's side-chain cleavage, which constitute the limiting step in steroidogenesis, were studied by measuring oxygen consumption rates in the presence of cholesterol derivatives. The addition of (20R)-hydroxycholesterol, (22R)-hydroxycholesterol or (20R,22R)-dihydroxycholesterol stimulated these rates, but addition of cholesterol or (22S)-hydroxycholesterol had little effect. Thyroidectomy significantly reduced oxygen consumption rates in the presence of the sterols by about 30%. Oxygen uptake was small in the presence of respiratory inhibitors; the addition of sterols raised this uptake but subsequent thyroidectomy did not change it. Rat adrenal cortex mitochondria and microsomes converted pregnenolone ino progesterone through 3 beta ol dehydrogenase/delta 4-5 isomerase, in two different successive steps. Values for enzyme activities were 0.18, 0.26 and 0.81 nmol progesterone/min/mg protein for the overall complex, the 3 beta ol dehydrogenase and the delta 4-5 isomerase respectively. All enzyme activities were unchanged by thyroidectomy. Similar results were obtained for corresponding microsomal activities whose values were in the same range. For both microsomes and mitochondria, the dehydrogenase reaction was the limiting step in the enzyme reaction leading to progesterone formation from pregnenolone. The limiting step in corticosteroidogenesis leading to prenenolone formation by an NADPH-dependent step was slowed down by thyroidectomy, probably because the reaction that transfers energy from NADH to NADP was inhibited. The enzyme complex leading to progesterone which involves NAD+ as cofactor, was unchanged by thyroidectomy. Thyroid hormones may therefore affect the availability of the energy mechanisms connected with the proton motive force, since thyroidectomy reduces both the phosphorylative oxidation and energy-dependent hydroxylation reactions involved in steroidogenesis.

Adrenal Cortex↗

Effect of thyroidectomy on the rat adrenal cortex enzyme activities involved in corticosterone and aldosterone biosynthesis.

The effect of thyroidectomy on corticosterone and aldosterone biosynthesis, in rat adrenal cortex, were investigated in vitro. Thyroidectomy slowed down by about 30% the activity of microsomal 21 hydroxylase and mitochondrial 11 beta hydroxylase, the two stages leading to corticosterone formation from progesterone. The plasma corticosterone concentration also diminished in thyroidectomized rat. The mitochondrial enzyme system catalyzing the conversion of corticosterone into aldosterone included both 18 hydroxylase and 180H dehydrogenase. In the absence of thyroid hormone, values of both enzyme activity slowed down by about 30%. Thus thyroidectomy induced a general decrease in all mitochondrial hydroxylation processes requiring NNADPH as energetic cofactor. Mitochondrial NADPH was mainly synthesized by the activity of NADP+ malic enzyme and pyridine nucleotide transhydrogenase; the activity of both enzymes was determined in submitochondrial particles from adrenal cortex of normal and thyroidectomized rats. The activity of NADP+ malic enzyme and non energy-dependent transhydrogenase in the direction of NADPH formation dropped significantly after thyroidectomy, thus reducing the amount of NADPH available for hydroxylating mechanisms. The results should be compared to the large rise in th cytosolic malic enzyme level caused by thyroidectomy. The latter also ensured that the transhydrogenase reaction did not vary in the direction of NADP+ formation. Further, the drop in NADPH synthesis after thyroidectomy was coupled with a decrease in phosphorylation rate of added ADPH by adrenal cortex mitochondria of thyroidectomized rat. These findings might account for the general decline in the energy-dependent processes involved in steroidogenesis, a decline mainly due to the lowering of the H+ ions gradient driving ATP and NADPH synthesis through electron transfer.

Adrenal Cortex↗

[Effects of 3,5,3'-triiodothyroacetic acid (TRIAC) on protein metabolism of genetically obese or non-obese Zucker rats].

Genetically obese female rats (fa/fa) and their lean littermates (Fa/-) were given oral administration of 3,5,3-triiodothyroacetic acid (TRIAC) (20 micrograms/ 100 g of body weight/ day) during 4 weeks. Metabolism of proteins was evaluated in several organs and in skeletal muscle after intraperitoneal injection of 14C and 3H-leucine 6 days and 16 hrs respectively before the sacrifice of animals. We have determined radioactivity of 14C and 3H and the 3H/14C ratio. No significant differences were found in lean and obese rats except in skeletal muscle. The relative protein turnover in skeletal muscle is significantly higher in the obese rats than in the lean rats. Treatment by TRIAC decreases the body weight gain in obese rats compared with controls but it has no statistically significant effect on the relative protein turnover in either obese or lean rats.

Animals↗

[Effect of methylmercury chloride on mitosis in human lymphocytes in culture: ultrastructural study].

The ultrastructural study of proliferating human lymphocytes poisoned by methylmercury chloride, shows that this product disorganizes and alters the different constituents of the mitotic figure. The chromosomes, partially decondensed, are covered with protuberances and connected by various chromatin bridges. Tubular structures are changed. In disorganized cellular centers, the badly bounded centrioles are often thickened. Membraneous systems are altered.

Cells, Cultured↗

Serum inhibitory effect on myeloperoxidase in human cancer.

The myeloperoxidase level is strongly depressed in leucocytes from cancer patients (-59%). Moreover sera of the same subjects induce a significant decrease in the myeloperoxidase activity of healthy subjects' leucocytes (-43%). We have found no convincing evidence of any correlation between the level of the inhibitory effect of sera and the tumour type. The fact that sera from cancer patients interfere with neutrophil responses in this way does not exclude the possibility that abnormal cellular functions were also operative.

Adult↗

[Isolation of free-living amoebae from nasal mucosa of healthy individuals].

In 13 out of 140 recruits examined (9.3%) one or several species of Acanthamoeba were identified in smears of the nasal mucosa. From among 20 isolated strains of amoebae the following species were determined: Acanthamoeba castellanii (42.2%), A. polyphaga (31.5%), A. palestinensis (26.3%), A. astronyxis (5.3%). The persons contaminated with amoebae were in good health at the time of sampling. It is assumed that an aerogenic contamination of the carriers took place.

Adolescent↗

[Brain mitochondrial and nuclear activity of the thyroidectomized rat].

A rapid method of preparation of rat brain mitochondria was described. Oxidative phosphorylation of isolated brain mitochondria was decreased by thyroidectomy. RNA polymerase activity of isolated nuclei was also reduced. Therefore hypothyroidism affects brain subcellular particles as in other tissues.

Animals↗

[Acute toxicity of two phenylcarbamates: propham and chloropropham].

The bibliographic data dealing with the acute toxicity of two phenylcarbamates, propham and chloropropham, are not very precise an often contradictory. This work is a restatement and also a demonstration of the high sensitivity of the aquatic animals that we have tested (Amphibia and Crustacea) in comparison with the Mammals (rat and mouse).

Animals↗

[Effects of propham and chlorpropham on the embryonic development of various vertebrates].

The effect of propham and chlorpropham on Amphibians embryonic development changes with doses as well as species. The action of C.I.P.C. is always determinative. The egg poisoned in albumen involves important chick embryo malformations, but the development is stopped by the yolky vesicle poisoning. The intraperitoneal injection of C.I.P.C., strongly disturbs fetus physiology in Mouse.

Animals↗