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M Miko

Publications and source records attributed to M Miko.

At least 55 records · Page 3Linked to original sources

Effect of chloro- and bromo-derivatives of isocrotonic acid of bioenergetic processes in Ehrlich ascites cells and isolated mitochondria.

The effect of nine chloro- and bromoderivatives of isocrotonic acid on some bioenergetic processes in both Ehrlich ascites cells and isolated rat liver mitochondria has been investigated. Substances studied in the concentration range 25--200 microM significantly inhibited incorporation of both 14C-adenine and 14C-valine into acid-insoluble material of Ehrlich ascites cells. The rate of 14C-precursors incorporation being directly related to the concentration of the inhibitor. Gamma,gamma-bis-4-ethylphenyl-alpha,beta-dichloroisocrotonic acid fully inhibits both aerobic glucose utilization and lactic acid formation at 200 microM concentration. At lower concentrations, however, glycolysis is stimulated. Maximal stimulation of rat liver mitochondrial respiration in state 4 with succinate as substrate was reached at concentrations as low as 10 microM. On the other hand, these substances were able to release by the oligomycin inhibited respiration of rat liver mitochondria. Our data suggest that cytotoxic and cancerostatic action of isocrotonic acid derivatives lies primarily in the exclusion of key processes in the energy metabolism of Ehrlich ascites cells and isolated mitochondria.

Animals↗

Cytotoxic and cancerostatic effect of 1,4-dithiaanthraquinone-2,3-dicarbonitrile.

1,4-Dithiaanthraquinone-2,3-dicarbonitrile (DTA) has been found to exert a considerable cytostatic effect especially on some of the investigated types of eukaryotic cells, concretely on the HeLa cells, moulds, yeasts, protozoa and algae. In cells of the Ehrlich ascites carcinoma (EAC) DTA after a short exposition causes a parallel inhibition of incorporation of 14C-adenine and 14C-valine, in proportion to its rising concentration. The inhibition of biosynthetic processes thus made manifest, is probably a consequence of the primary DTA intervention into the energy metabolism of EAC cells, particularly in glycolysis. The effect of DTA in concentrations capable of bringing about full inhibition of glucose consumption or lactate formation in EAC cells also results in a loss of their transplantability. On the other hand, DTA also exerts a cancerostatic effect on the Ehrlich ascites carcinoma in mice.

Animals↗

Isothiocyanates. A new class of uncouplers.

This paper describes the uncoupling effect of three isothiocyanates: p-bromophenylisothiocyanate, 4,4'-diisothiocyanatebiphenyl and beta-naphtylemthylisothiocyanate on the respiration of Ehrlich-Lettré cells and isolated mitochondria. The isothiocyanates are similar to other uncouplers (such as 2,4-dinitrophenol and carbonyl cyanide p-trifluoromethoxyphenylhydrazone) in that they: 1. stimulate respiration of state 4 mitochondria; 2. stimulate mitochondrial ATPase activity; 3. release the inhibition of mitochondrial respiration by oligomycin and 4. inhibit both mitochondrial respiration and mitochondrial ATPase activity at higher molar concentrations. The incoupling activity of these isothiocyanates correlates well with their biological activity. Maximal activation of a latent mitochondrial ATPase activity of rat liver mitochondria in the presence of p-bromophenylisothiocyanate was found at a concentration of 15 muM. The investigated isothiocyanates differ significantly in their solubility in organic solvents and their chemical reactivity. We assume that the greater the partition coefficient in a series of isothiocyanates grouped according to the increasing value of log P (partition coefficient for the system octanol/water, 25 degrees C), the greater will be their uncoupling activity, but only up to a certain degree. Any further increase of log P will be marked by a decrease of this activity.

Adenosine Triphosphatases↗

Diclofenac sodium (Voltaren): results of a multi-centre comparative trial in adult-onset rheumatoid arthritis.

A short-term trial has been performed under double-blind conditions in 50 adult patients with rheumatoid arthritis to compare diclofenac sodium (Voltaren) with both indomethacin and placebo for efficacy and tolerability. The duration of the trial was two weeks and was a between-patient comparison of 25 mg t.i.d. diclofenac sodium, 25 mg t.i.d. indomethacin or placebo using a double-dummy technique. Forty-eight patients completed the trial. In the majority of parameters examined, diclofenac sodium was superior to placebo and indomethacin in therapeutic effect. One patient was withdrawn from the trial because of intolerance to indomethacin and one other because of severe joint pain under indomethacin therapy. Neither active compound caused clinically significant changes in blood picture or urine analysis.

Adult↗