The glutathione defense system in the pathogenesis of rheumatoid arthritis.

In order to assess a possible role of the natural glutathione defense system in the pathogenesis of rheumatoid arthritis (RA), serum reduced glutathione levels (GSH), glutathione reductase (GSR), glutathione S-transferase (GST), glutathione peroxidase (GSH-Px) and alkaline phosphatase (ALP) activities, lipid peroxidation (MDA content) and indexes of inflammation were evaluated in 58 rheumatic patients. Rheumatoid athritis was associated with significant depletion (ca. 50%) in GSH levels compared with normal control subjects. Serum levels of the detoxifying enzymes GSR and GSH-Px decreased by ca. 50% and 45%, respectively, whereas a threefold increase in the activity of GST was observed. A 1.2-fold increase in ALP was observed in patients with RA. These effects were accompanied by a 3.1-fold increase in serum MDA content. The MDA content was higher in RA patients who were seropositive for rheumatoid factor as well as positive for C-reactive proteins. The erythrocyte sedimentation rate for all patients with RA was approximately 13.8-fold higher than for the control group, and was higher among RA patients who were positive for C-reactive proteins and exhibited seropositivity for rheumatoid factor. Patients with RA receiving gold therapy exhibited significantly lower MDA levels whereas all other factors that were measured were not effected. The results support a hypothesis that defense mechanisms against reactive oxygen species are impaired in RA.

Protection by selective amino acid solutions against doxorubicin induced growth inhibition of Escherichia coli.

1. Incubation of Escherichia coli with 0.7 mM doxorubicin in MBS-glucose medium resulted in complete growth inhibition, an inhibition that was blocked by placing specific amino acids (AA) in the medium. 2. The mechanism of protection by AA was similar to that reported previously for cells poisoned by hyperoxia and by paraquat, e.g. of 20 common AA, ten percent, ten do not and the branched-chair AA are among those required for inhibition. 3. Unlike hyperoxia and paraquot stringency which caused elevation of intracellular concentrations of guanosine tetraphosphate (ppGpp), doxorubicin inhibition did not elevate ppGpp. 4. Concentrations of ppGpp were increased by isoleucine starvation as expected, and the subsequent addition of doxorubicin did not abolish that increase; however, pretreatment with doxorubicin prevented the induction of stringency by isoleucine starvation. 5. This suggests that doxorubicin directly inhibits ppGpp synthesis or protein biosynthesis to leave tRNA loaded as is the case with chloramphenicol.

Inactivation of aminoglycosides against Pseudomonas aeruginosa by a nutrition supplementation solution.

1. Possible interference of a nutritional solution (Vamin) with the activity of several aminoglycosides against Pseudomonas aeruginosa was evaluated in vitro. 2. Inactivation in cultures of 0.75, 1.2, 2.8, 65 micrograms/ml of gentamicin, kanamycin, amikacin, streptomycin, and tobramycin was induced by the addition of 1:20 v/v of the nutritional solution. 3. This inactivation was due to the presence of specific amino acids in the mixture. Deletions of amino acids from the media and amino acid analysis of the cellular pool revealed that valine, leucine, isoleucine, tyrosine, tryptophan, phenylalanine, cysteine, methionine, or threonine were responsible for the inactivation. 4. The concentration of threonine decreased in kanamycin and amikacin treated cells suggesting that certain aminoglycoside antibiotics undergo a decrease in activity when sensitive Ps. aeruginosa are treated with a nutrient solution. 5. Specific amino acids may interfere with the activity of antibiotics by circumventing their effect on amino acid biosynthesis.

In vitro production of estriol from four steroid precursors by rabbit tissues.

The production of estriol was demonstrated in intact leukocytes and homogenates of liver, adrenals and ovaries of young adult female rabbits from 17 beta-estriol, testosterone, androst-4-ene-3,17-dione and dehydroepiandrosterone. Androst-4-ene-3,17-dione constituted the best substrate in liver and adrenals and the poorest substrate for estriol production in lymphocytes. Estriol was least readily transformed into estriol in liver and adrenals, while it proved to be the best substrate in ovaries. Phenobarbital administration to rabbits resulted in 49-fold and 23-fold increases in the transformation of androst-4-ene-3,17-dione and dehydroepiandrosterone, respectively, into estriol by lymphocytes. The results indicate that the enzymes involved in estriol biosynthesis in the various tissues respond differently to phenobarbital.