Treatment of cutaneous ulcers with benzoyl peroxide.
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Benzoyl peroxide, a powerful organic oxidizing agent, was applied topically according to a carefully developed technique to cutaneous ulcers of different types. The healing time was shortened greatly by the rapid development of healthy granulation tissue and the quick ingrowth of epithelium. Exceptionally large pressure ulcers with deep cavities, undercut edges and sinus tracts were sucessfully treated, as were stasis ulcers of long duration resistant to all other therapy. There were only 13 treatment failures among the 133 cases. The slow, sustained release of oxygen by benzoyl peroxide was though to be responsible for the success. The only complications were contact irritant dermatitis in 3% and contact allergic dermatitis in 2% of patients treated. (+info)
Metabolism of the antimalarial endoperoxide Ro 42-1611 (arteflene) in the rat: evidence for endoperoxide bioactivation.
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Ro 42-1611 (arteflene) is a synthetic endoperoxide antimalarial. The antimalarial activity of endoperoxides is attributed to iron(II)-mediated generation of carbon-centered radicals. An alpha, beta-unsaturated ketone (enone; 4-[2',4' bis(trifluoromethyl)phenyl]-3-buten-2-one), obtained from arteflene by reaction with iron(II), was identified previously as the stable product of a reaction that, by inference, also yields a cyclohexyl radical. The activation of arteflene in vivo has been characterized with particular reference to enone formation. [14C]Arteflene (35 micromol/kg) was given i.v. to anesthetized and cannulated male rats: 42.2 +/- 7.0% (mean +/- S.D., n = 7) of the radiolabel was recovered in bile over 5 h. In the majority of rats, the principal biliary metabolites were 8-hydroxyarteflene glucuronide (14.2 +/- 3. 9% dose, 0-3 h) and the cis and trans isomers of the enone (13.5 +/- 4.6% dose, 0-3 h). In conscious rats, 15.3 +/- 1.6% (mean +/- S.D., n = 8) of the radiolabel was recovered in urine over 24 h. The principal urinary metabolite appeared to be a glycine conjugate of a derivative of the enone. Biliary excretion of the glucuronide, but not of the enones, was inhibited by ketoconazole. 8-Hydroxyarteflene was formed extensively by rat and human liver microsomes but no enone was found. Bioactivation is a major pathway of arteflene's metabolism in the rat. Although the mechanism of in vivo bioactivation is unclear, the reaction is not catalyzed by microsomal cytochrome P-450 enzymes. (+info)
Paraquat toxicity: proposed mechanism of action involving lipid peroxidation.
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The purpose of this study was to investigate the hypothesis that paraquat pulmonary toxicity results from cyclic reduction-oxidation of paraquat with sequential generation of superoxide radicals and singlet oxygen and initiation of lipid peroxidation. In vitro mouse lung microsomes catalyzed an NADPH-dependent, single-electron reduction of paraquat. Incubation of paraquat with NADPH, NADPH-cytochrome c reductase, and purified microsomal lipid increased malondialdehyde production is a concentration dependent manner. Addition of either superoxide dismutase or a single oxygen trapping agent 1,3-dipheylisobenzo furan inhibited paraquat stimulated lipid peroxidation. In vivo, pretreatment of mice with phenobarbital decreased paraquat toxicity, possibly by competing for electrons which might otherwise reduce paraquat. In contrast, paraquat toxicity in mice was increased by exposure to 100% oxygen and by deficiencies of the antioxidants selenium, vitamin E, or reduced glutahione (GSH). Paraquat, given IP to mice, at 30 mg/kg, decreased concentrations of the water-soluble antioxidant GSH in liver and lipid soluble antioxidants in lung. Oxygen-tolerant rats, which hae increased activities of pulmonary enzymes which combat lipid peroxidation, were also tolerant to lethal doses of paraquat as indicated by an increased paraquat LT50. Furthermore, rats chronically exposed to 100 ppm paraquat in the water had elevated pulmonary activities of glucose-6-phosphate dehydrogenase and GSH reductase. These results were consistent with the hypothesis that lipid peroxidation is involved in the toxicity of paraquat. (+info)
Inhibition of the peroxidative degradation of haem as the basis of action of chloroquine and other quinoline antimalarials.
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The malaria parasite feeds by degrading haemoglobin in an acidic food vacuole, producing free haem moieties as a by-product. The haem in oxyhaemoglobin is oxidized from the Fe(II) state to the Fe(III) state with the consequent production of an equimolar concentration of H2O2. We have analysed the fate of haem molecules in Plasmodium falciparum-infected erythrocytes and have found that only about one third of the haem is polymerized to form haemozoin. The remainder appears to be degraded by a non-enzymic process which leads to an accumulation of iron in the parasite. A possible route for degradation of the haem is by reacting with H2O2, and we show that, under conditions designed to resemble those found in the food vacuole, i.e., at pH5.2 in the presence of protein, free haem undergoes rapid peroxidative decomposition. Chloroquine and quinacrine are shown to be efficient inhibitors of the peroxidative destruction of haem, while epiquinine, a quinoline compound with very low antimalarial activity, has little inhibitory effect. We also show that chloroquine enhances the association of haem with membranes, while epiquinine inhibits this association, and that treatment of parasitized erythrocytes with chloroquine leads to a build-up of membrane-associated haem in the parasite. We suggest that chloroquine exerts its antimalarial activity by causing a build-up of toxic membrane-associated haem molecules that eventually destroy the integrity of the malaria parasite. We have further shown that resistance-modulating compounds, such as chlorpromazine, interact with haem and efficiently inhibit its degradation. This may explain the weak antimalarial activities of these compounds. (+info)
Biotransformation of (1-phenyl)ethyl hydroperoxide with Aspergillus niger: a model study on enzyme selectivity and on the induction of peroxidase activity.
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The biocatalytic enantioselective reduction of (1-phenyl)ethyl hydroperoxide (1) by the fungus Aspergillus niger to the corresponding alcohol 2 involves a multi-enzyme biotransformation of the hydroperoxide 1, as revealed by the change in the enantioselectivity as a function of incubation times. This unusual behavior is not exhibited by other fungi and seems to be restricted to A. niger. Furthermore, the peroxidase and other oxidoreductase activities of A. niger depend on the availability of metal ions such as Fe2+, Mn2+ and Zn2+ in the growth medium, since the addition of Fe2+ ions substantially (threefold) increases the enantioselectivity, whereas addition of Mn2+ and Zn2+ ions decreases it. Finally, the cold shock (4 degrees C) significantly enhances the reduction of the hydroperoxide by the microorganism A. niger. (+info)
Clinical trial of three 10% carbamide peroxide bleaching products.
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BACKGROUND: A profusion of commercial bleaching systems exists on the market today, but there are few clinical comparisons of these systems. METHODS: In this study, three different commercial 10% carbamide peroxide bleaching systems were used by 24 patients in an overnight protocol for two weeks. Each patient used two of the bleaching products simultaneously in a side-by-side comparison. RESULTS: The mean onset of tooth whitening was 2.4 +/- 1.7 days. Tooth sensitivity was the most frequent side effect, as 64% of the patients reported tooth sensitivity occurring after 4.8 +/- 4.1 days and lasting for 5.0 +/- 3.8 days. Although intrapatient differences were recorded for the three commercial 10% carbamide peroxide bleaching systems by the patients, there were no statistical differences in the time of onset of subjective tooth whitening and the onset, frequency and duration of tooth sensitivity among the three commercial bleaching systems when compared pairwise or independently (p < 0.05). CONCLUSION: Selection of which bleaching product to use should be based on the concentration of the active ingredient, the viscosity of the product and other marketing features. Further research is needed to investigate the causes of tooth sensitivity and methods to reduce its severity and frequency. (+info)
The effect of aging and an oxidative stress on peroxide levels and the mitochondrial membrane potential in isolated rat hepatocytes.
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We have investigated the effect of ageing and of adriamycin treatment on the bioenergetics of isolated rat hepatocytes. Ageing per se, whilst being associated with a striking increase of hydrogen peroxide in the cells, induces only minor changes on the mitochondrial membrane potential. The adriamycin treatment induces a decrease of the mitochondrial membrane potential in situ and a consistent increase of the superoxide anion cellular content independently of the donor age. The hydrogen peroxide is significantly increased in both aged and adult rat hepatocytes, however, due to the high basal level in the aged cells, it is higher in aged rat cells not subjected to oxidative stress than that elicited by 50 microM adriamycin in young rat hepatocytes. The results suggest that a hydrogen peroxide increase in hepatocytes of aged rats is unable to induce major modifications of mitochondrial bioenergetics. This contrasts with the damaging effect of adriamycin, suggesting that the effects of the drug may be due to the concomitant high level of both superoxide and hydrogen peroxide. (+info)
Antioxidant activity of a medicine based on Aspergillus oryzae NK koji measured by a modified t-butyl peroxyl radical scavenging assay.
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A koji-based medicine composed of powder of Aspergillus oryzae NK koji, dried yeast, and lactobacilli koji had high antioxidant activity measured by a modified t-butyl peroxyl radical scavenging assay. This activity was mainly derived from A. oryzae NK koji. Digestion of koji-making grain germ medium with several commercial enzymes also increased antioxidant activity. By two weeks of oral administration of A. oryzae NK koji, the serum lipid peroxide levels elevated in STZ-induced diabetic rats could be decreased significantly. (+info)