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PubMed1980

[Effect of 2,3-dimercaptopropanol on electron transfer in the energy coupling site 2 of the respiratory chain: evidence for the Q-cycle hypothesis].

Incubation of submitochondrial particles from bovine heart with 2,3-dimercaptopropanol (British antilewisite, BAL) results in inhibition of the respiratory chain between cytochromes b and c. BAL exerts no pronounced effect on the spectral and redox properties of cytochromes b566 and b562. In the BAL-treated submitochondrial particles antimycin brings about the bathochromic shift of the cytochrome b562 absorption alpha-band, but does not induce "extra-reduction" of cytochromes b. Upon a combined effect of antimycin and BAL the reduction of cytochromes b by succinate is inhibited. Whereas neither antimycin nor BAL alone prevents this reaction. The data obtained suggest the existence of two pathways of electron transfer from succinate to cytochromes b, one of which is blocked by antimycin and the other one by BAL. These two pathways form a cyclic loop of electron transport, in accordance with the Mitchell's "protonmotive CoQ-cycle" hypothesis. The traditional scheme of linear arrangement of the respiratory carriers in the succinate--cytochrom c reductase span of the electron transfer chain, as well as the Wikstrom--Berden's branched model, do not provide satisfactory explanation of the mode of BAL inhibitory action.

Animals↗
PubMed1981

Structural requirements for chelate antidotal efficacy in acute antimony(III) intoxication.

The LD50 for i.p. potassium antimonyl tartrate was determined to be 54.6 mg/kg in mice, with a 95% confidence range of 48.4 to 61.7 mg/kg. An examination of the antidotal efficacy of a number of different structural types of chelating agents showed that very few types were able to act as antidotes when potassium antimonyl tartrate was administered i.p. to mice at a level of 120 mg/kg. The most effective antidotes, by a substantial margin, were the water soluble vicinal dithiols: 2,3-dimercaptosuccinic acid and sodium 2.3-dimercaptopropane-1-sulfonate, with the first of these being significantly better than the second. Appreciably less effective, but still useful, was D-penicillamine. At this level of administration of antimony(III), BAL is not an effective antidote. Among other chelating agents which were also not effective at this level of antimony(III) are tartaric acid, EDTA, cysteine, sodium diethyldithiocarbamate and potassium dithiooxalate.

Animals↗
PubMed1981

[Sodium 2,3-dithiopropanesulfate blockade of the effect of cholera enterotoxin on adenylate cyclase and the concentration of cyclic 3',5'-adenosine monophosphate in the small intestine mucosa of the rabbit].

Activation of adenylate cyclase in membrane preparations of the rabbit small intestine mucosa by cholera enterotoxin in the presence of sodium 2,3-dithiopropanesulfate (DTPS) is similar to that in the presence of dithiothreitol (DTT). Both DTT and DTPS do not influence the activity of adenylate cyclase without cholera enterotoxin. DTPS activates cyclic 3,5-AMP phosphodiesterase of mucosa homogenates (K0.5 = 10(-5) M). Combined administration of cholera enterotoxin and DTPS in situ into isolated loops of the rabbit small intestine decreases the activating effect of cholera enterotoxin on adenylate cyclase and diminishes the content of cyclic AMP in the mucosa. The destruction of disulfide bonds of cholera enterotoxin by DTPS is assumed to lower its ability to penetrate the mucosal cells of the small intestine.

Adenylyl Cyclases↗
PubMed1982

[Inhibition of H2O2 and O2-. generation in the respiratory chain, treated with 2,3-dimercaptopropanol].

Inhibition of electron transport in bovine heart submitochondrial particles resulting from treatment with British antilewisite is accompanied by suppression of superoxide radical and H2O2 generation at the b-c1 site of the respiratory chain. In conjunction with the previously obtained data, the results suggest that the effect of British antilewisite is directed towards the step of ubihydroqinone oxidation to ubisemiquinone by the Rieske FeS-protein.

Animals↗
PubMed1984

A systematic survey of HLA-A,B,C and D antigens and drug toxicity in rheumatoid arthritis.

One hundred sixty-two consecutive patients with rheumatoid arthritis (RA) were studied for possible association between HLA antigens, particularly DR antigens, and disease characteristics and adverse reactions to gold or D-penicillamine treatment. The frequency of HLA-DR4 was significantly increased: 62% in RA compared to 23% in controls. An association of HLA-DR4 with a positive family history for RA was also found. HLA-DR4 was not associated with subcutaneous nodules or keratoconjunctivitis, presence of rheumatoid factor, or ANA positivity. No increased prevalence of HLA-DR3 was found in patients who developed drug related toxicity (e.g., proteinuria for gold or D-penicillamine). Of the 27 patients in whom proteinuria developed, only 5 were DR3 positive. A significant association with D-penicillamine induced proteinuria and HLA-B8 gene was found. Our results obtained in a systematic survey do not confirm previous reports of a significant association between HLA-DR3 and drug toxicity, but confirm the association between HLA-DR4 and the development of RA and HLA-B8 and D-penicillamine induced proteinuria.

Adolescent↗
PubMed1983

[Lead poisoning].

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Adrenal Cortex Hormones↗
PubMedDate not supplied

[Penetration and binding strength of cadmium and its complexes with dithiols in cells].

It was shown in experiments with three types of cells (dog red cells, hepatic cells of newborn Wistar rats, and culture of the renal epithelium of Vero monkeys) that cadmium in complexes with dimercaptoethanol penetrates the cells in an 8-33-fold greater amounts than free cations of metal. Unithiol increases cadmium penetration in the cells by 1.6-3 times only. The strength of cadmium binding with dimercaptopropranolol in the cells is greater than that with unithiol and free cations. Albumin limits penetration of free cations of cadmium and of complexes with dimercaptothiol to a greater degree than that of cadmium complexes with unithiols. The reasons for the differences revealed are discussed.

Absorption↗
PubMed1981

[Ultrastructural and microanalytic study of gold depots in the synovial membrane of man and animals during treatment with sodium aurothiopropanol sulfonate].

In inflammatory rheumatism treated by gold therapy synoviocytes A are stuffed with gold salt deposits leading to a therapeutic thesaurismosis. These deposits are localized in lysosomes, then called aurosomes. However they may be rarely near collagen fibers or free, particularly in ankylosing spondylitis synovitis. Their structural morphological aspect is the same in several human rheumatic diseases and in rabbit experimental arthritis whatever the gold salt used. In such deposits, microprobe analysis shows gold and sulphur. This latter is probably given by the cell. Therapeutic effect of gold salts may imply the effect of the thiol moiety and the gold metal one.

Adult↗
PubMedDate not supplied

[Hepatitis secondary to a gold salt overdose].

The authors report the case of a 51-year-old woman who developed cholestatic and cytolytic hepatitis after an overdose of sodium aurothiopropanol sulfonate 1.1 g, namely 300 mg gold metal. Liver biopsy demonstrated cholestasis, centrolobular steatosis and portal fibrosis. Electron microscopy showed abundant lipo-pigments in the hepatic and cellular cells, as well as myelinic bodies. Gold analysis by atomic absorption spectroscopy showed a level of 22.76 micrograms per ml in the plasma and a level of 2.16 micrograms per g in the liver. Chelating agents increased the urinary gold excretion, but were without effect on the course of hepatitis. Dimercaptopropanol seemed to favor the occurrence of other gold salt side-effects and penicillamine increased the hepatic cytolysis. The patient recovered without sequelae.

Anti-Inflammatory Agents↗
PubMed1984

[Unithiol in the treatment of secondary amyloidosis patients].

Seventy-five patients with secondary amyloidosis were treated with unithiol. Good objective results were obtained in 19 patients, who demonstrated considerable improvement of the general well-being, reduction in proteinuria, edemas, appreciable elevation of the levels of total protein. albumins and sulfhydryl groups in blood serum. Satisfactory results were obtained in 18 patients who showed a certain improvement of the general well-being, moderate drop of proteinuria, elevation of the levels of albumins and sulfhydryl groups in blood serum. Twenty-four patients noted only subjective improvement. Fourteen patients did not respond or showed deterioration of the health status. Three patients developed allergic rash which disappeared after drug discontinuation and administration of the common desensitization agents.

Amyloidosis↗