Cyclosporine (Cys A) is a potent immunosuppressor used to reduce rejection in transplantation surgery. We studied its action upon mitochondrial functions: oxidative phosphorylation and Ca2+ movements through mitochondrial membrane. We show that Cys A exhibits an inhibitory effect upon mitochondrial respiration. This result is in good agreement with previous works and may be correlated with Cys A toxicity. The action of cyclosporine on calcium fluxes is more pronounced. Indeed it blocks mitochondrial calcium efflux and allows mitochondria to accumulate a large amount of calcium. If this effect occurs in the cell, it would induce a Ca2+ decrease in cytosol. This action might be correlated with the inhibitory effect of Cys A upon the mitogenic stimulation of T lymphocytes.

Animals↗

PubMed1987

Interaction of some estrogenic drugs with tubulin. Formation of twisted ribbon structures.

We studied the action of E-diethylstilbestrol (E-DES), erythro-hexestrol (erythro-HES), and E,E-dienestrol (E,E-DIES) on microtubule formation. The three drugs inhibit this formation from microtubular protein; the percentages of inhibition were, respectively, 15% and 45% for 1.25 X 10-s M E-DES and E,E-DIES. With purified tubulin 6S, 7.5 X 10(-6) M E,E-DIES and erythro-HES induced a 20% inhibition. In the case of E-DES, our results are in good agreement with previous ones. These drugs partially disrupt preformed microtubules. Moreover, when E,E-DIES (5 X 10(-5) M) is added to tubulin, loosely organized aggregates composed of twisted ribbon structure are formed. In the case of erythro-HES, similar structures were observed but at higher concentrations. With E-DES, no organized structures are present.

Animals↗

PubMed1987

Comparative study of bepridil and nicardipine action on respiration and calcium transport in mitochondria.

Effects of the calcium antagonists bepridil and nicardipine on mitochondrial functions were studied and their effects on respiratory control and calcium fluxes were compared. Results show that bepridil and nicardipine similarly increase Ca2+ intracellular movements, but that intramitochondrial Ca2+ storage is increased by bepridil whereas it is decreased by nicardipine. The in vivo significance of these findings remain to be determined. The effect of bepridil might be related to an enhancement of mitochondrial ATPase activity whereas nicardipine would act on mitochondria by a different mechanism.

Adenosine Triphosphatases↗

PubMed1987

31P nuclear magnetic resonance study of variations in intra-erythrocytic ATP concentration and pH induced by surgical trauma.

Variations in intracellular pH and ATP concentrations in erythrocytes were studied in patients undergoing a mild surgical intervention. Intra-erythrocytic pH was decreased at the end of the operation; ATP concentrations concomitantly increased, but not highly significantly. These variables returned to their initial values by 20 h after the end of surgery.

Adenosine Triphosphate↗

PubMed1987

Modification of intra-erythrocytic homeostasis in uremic patients, as studied with 31P nuclear magnetic resonance.

Intra-erythrocytic pH, ATP concentrations, and 2,3-diphosphoglycerate relaxation times were studied in living erythrocytes by "high-resolution" 31P NMR spectroscopy to assess homeostasis within the cells. In uremic patients, intra-erythrocytic pH is significantly decreased before hemodialysis, but is corrected equally well by hemodialysis against either acetate or bicarbonate. This acidic pHi may be correlated with the increased concentration of ATP in erythrocytes in uremia, which is partly corrected by these two types of hemodialysis. Similarly, the significant decrease of spin-spin relaxation times in uremic patients is corrected by hemodialysis.

Acetates↗

PubMed1986

Action of vinca alkaloides on calcium movements through mitochondrial membrane.

The antimitotic drugs Vinblastine and Vincristine partially counteract the decoupling effect of both calcium ionophore and Ca2+ on mitochondria. The partial restoration of respiratory control is mainly due to an action on oxidative rate in state 4. In the same manner the P/O ratio is partially restorated. Moreover Vinca alkaloides decrease both the calcium uptake rate and its amount into mitochondria during aerobiosis and slacken the calcium efflux. These results may be explained by a non specific effect of Vinca alkaloides on mitochondrial membrane and might lead to a change in cytoplasmic Ca2+ concentration. Recently, calcium influx blockers (calcium antagonists) have appeared to enhance the cytotoxicity of Vinca alkaloides and to circumvent the Vincristine resistance of some tumor cells (Takashi Tsuruo et al. 1981, 1983). Besides, ruthenium red is a membrane inorganic dye known to bind and inhibit some calcium carriers (mitochondrial carrier, ATP ase calcium dependent from sarcoplasmic reticulum and erythrocyte). This dye has proved to increase the Vinblastine cell accumulation and its toxicity on cells culture (Wilberding C. 1984). So calcium might be involved in the therapeutic activity of Vinca alkaloides. Therefore, in order to investigate this possible implication we studied the effect of these drugs on calcium movements in mitochondria.

Animals↗

PubMed1986

[Persistent neurological syndrome after treatment with lithium salts. Toxicity of the lithium-neuroleptic combination?].

In 2 patients receiving a long-term lithium carbonate therapy, persistent cerebellar, pyramidal, and extrapyramidal signs were observed, following a febrile pulmonary event. The mechanism of these disturbances is discussed, emphasizing the lithium-neuroleptics interaction as well as the possible role of hyperthermia.

Adult↗

PubMed1986

[Treatment of amyotrophic lateral sclerosis with thyrotropin releasing hormone].

Nine patients (7 with amyotrophic lateral sclerosis, 1 with progressive spinal amyotrophy and 1 with chronic anterior poliomyelitis) were treated by sequential intravenous administration of 240 mg of TRH over one hour every two weeks. Results were assessed by an analytical evaluation of muscle strength before and 24 h after each infusion and by objective and subjective evaluation of spasticity. Significant improvement, as shown by statistical analysis, was noted in muscle strength in the 9 patients by 5 infusions over a 4-week period and a sub-group of 5 patients treated by 8 infusions over 10 weeks. Continued use of this therapy is justified by the need to determine its long-term effects and the psychological improvement noted in some patients after an even transient improvement in motor performance. However this treatment is obviously not curative.

Adult↗

PubMed1986

Inhibition of microtubule formation by uremic toxins: action mechanism and hypothesis about the active component.

We show in vitro inhibitory effect of a mixture of uremic toxins on tubulin 6S polymerization. It proves the existence of a direct interaction protein-toxin where micro-tubule associated proteins are not involved. A similar phenomenom could occur in uremic neuropathy. The action mechanism of this interaction is quite different from that of classical tubulin inhibitors: Vinca alcaloïdes and colchicine. Finally we hypothesize about the active molecule.

Animals↗

PubMed1986

In vitro inhibition of microtubule assembly by disulfiram.

Disulfiram (Tetraethylthiuram disulfide, DSF) inhibits in vitro tubulin polymerization in a dose-dependent manner after a preliminary incubation time. Electron micrographs show that microtubules are shorter and less numerous. This inhibition may be correlated to blockade of protein SH groups. The linkage of DSF-tubulin hinders the vinca alkaloids-tubulin binding as shown using radioactive assay and microcalorimetric measurements. These results could be responsible for the occurrence of some side effects observed during the therapeutic use of this drug.

Animals↗

PubMed1986

Intra-erythrocytic sodium in uremic patients, as determined by "high-resolution" 23Na nuclear magnetic resonance.

The use of 23Na nuclear magnetic resonance with aqueous shift reagent has made it possible to determine intracellular sodium concentrations in living erythrocytes. We applied this technique to samples from 16 healthy subjects and 41 uremic patients. The results seem to show distinct populations among the latter. Classically, two different relaxation times are obtained for intracellular sodium in biological media, according to relaxation NMR theory. Some patients, however, exhibit abnormal results that cannot be accounted for by this theory.

Adult↗

PubMed1985

[Trial of thyrotropin-releasing factor in amyotrophic lateral sclerosis].

Explore the source record for details and available documents.

Amyotrophic Lateral Sclerosis↗

PubMed1985

Action on mitochondrial calcium metabolism of an ionophorous compound isolated from uremic plasma or normal urine.

An ionophorous compound that is one of the uremic middle molecules is able to inhibit the mitochondrial storage of calcium. Its active concentration is equivalent to that found in uremic plasma. This result can explain the diminution of phosphate calcium granules observed in mitochondria from uremic children. Moreover, this phenomenon may be involved in the calcium pool decrease observed in chronic renal insufficiency.

Animals↗

PubMed1985

A compound from uremic plasma and from normal urine isolated by liquid chromatography and identified by nuclear magnetic resonance.

A compound present in normal urine and in ultrafiltrates of uremic plasma in the fraction of so-called "uremic middle molecules" was isolated by liquid chromatography. Preliminary studies, including amino acid analysis, characterization of uronic acids, and ultraviolet spectroscopy, show that the molecule contains glycine, a uronic acid, and an aromatic ring. Characterization by 1H and 13C nuclear magnetic resonance spectrometry shows conclusively that this compound is a double conjugate of glucuronidate--o-hydroxyhippuric acid, which has been previously described by Zimmerman et al., using quite different techniques of isolation and identification (Clin Nephrol 14: 107, 1980; FEBS Lett 129: 237, 1981).

Chemical Phenomena↗