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V Fischer

Publications and source records attributed to V Fischer.

At least 73 records · Page 4Linked to original sources
PubMed1987

Formation of glutathione-conjugated semiquinones by the reaction of quinones with glutathione: an ESR study.

The nonenzymatic reaction of the cytotoxic compounds menadione (2-methyl-1,4-naphthoquinone) and 1,4-naphthoquinone (a reactive metabolite of 1-naphthol) with reducing agents such as NADPH and glutathione led to the formation of semiquinone-free radicals, which were detected with electron spin resonance spectroscopy. In the presence of glutathione as a reducing agent, menadione and 1,4-naphthoquinone underwent net one-electron reduction and conjugation with glutathione. At higher concentrations of glutathione, 1,4-naphthoquinone formed the semiquinones of both the monoconjugate and the diconjugate. The naphthoquinone-glutathione conjugates should redox cycle in a manner already known for the menadione conjugate. The semiquinone intermediates could be detected only under a nitrogen atmosphere and are probably the primary oxygen-reactive species responsible for the redox cycling of menadione- and naphthoquinone-glutathione conjugates.

Benzoquinones↗
PubMed1986

A search for oxygen-centered free radicals in the lipoxygenase/linoleic acid system.

Studies of the oxygenation of linoleic acid by soybean lipoxygenase utilizing electron spin resonance spectroscopy and oxygen uptake have been undertaken. The spin trap, alpha-(4-pyridyl-1-oxide)-N-t-butylnitrone (4-POBN) was included in the lipoxygenase system to capture short-lived free radicals. Correlation of radical adduct formation rates with oxygen uptake studies indicated that the major portion of radical adduct formation occurred when the system was nearly anaerobic. Incubations containing [17O]oxygen with nuclear spin of 5/2 did not have additional ESR lines as would be expected if an oxygen-centered 4-POBN-lipid peroxyl radical adduct were formed indicating that the trapped radical must be reassigned as a carbon-centered species. To establish the presence of [17O2]oxygen in our incubations, a portion of the gas from the lipoxygenase/linoleate experiments was used to prepare the 4-POBN-superoxide radical adduct utilizing a superoxide producing microsomal/paraquat/NADPH system.

Catalysis↗
PubMed1986

Direct electron spin resonance detection of free radical intermediates during the peroxidase catalyzed oxidation of phenacetin metabolites.

The oxidation of the phenacetin metabolites p-phenetidine and acetaminophen by peroxidases was investigated. Free radical intermediates from both metabolites were detected using fast-flow ESR spectroscopy. Oxidation of acetaminophen with either lactoperoxidase and hydrogen peroxide or horseradish peroxidase and hydrogen peroxide resulted in the formation of the N-acetyl-4-aminophenoxyl free radical. Totally resolved spectra were obtained and completely analyzed. The radical concentration was dependent on the square root of the enzyme concentration, indicating second-order decay of the radical, as is consistent with its dimerization or disproportionation. The horseradish peroxidase/hydrogen peroxide-catalyzed oxidation of p-phenetidine (4-ethoxyaniline) at pH 7.5-8.5 resulted in the one-electron oxidation products, the 4-ethoxyaniline cation free radical. The ESR spectra were well resolved and could be unambiguously assigned. Again, the enzyme dependence of the radical concentration indicated a second-order decay. The ESR spectrum of the conjugate base of the 4-ethoxyaniline cation radical, the neutral 4-ethoxyphenazyl free radical, was obtained at pH 11-12 by the oxidation of p-phenetidine with potassium permanganate.

Acetaminophen↗
PubMed1986

Formation of iminoxyl and nitroxide free radicals from nitrosonaphthols: an electron spin resonance study.

The possible metabolic activation of nitrosonaphthols, suspected carcinogens, was investigated by electron spin resonance (ESR) spectroscopy. Free radicals were found to be the primary metabolites formed during both the reduction and oxidation of these compounds. Whereas the one-electron oxidation of nitrosonaphthols is enzymatic and catalyzed by the peroxidase prototype, horseradish peroxidase, their one-electron reduction by reducing cofactors such as NADH or NADPH was not enhanced by rat liver microsomal enzymes. The ESR spectra of the radicals found during the oxidation of nitrosonaphthols were analyzed and characterized as iminoxyl free radicals. The reduction pathway leads to nitroxide free radicals with unusually low nitrogen hyperfine constants.

Carcinogens↗
PubMed1986

Free radicals of acetaminophen: their subsequent reactions and toxicological significance.

The oxidation of acetaminophen to the corresponding phenoxyl free radical and N-acetyl-p-benzoquinone imine by mammalian peroxidases is discussed. The acetaminophen free radical is very reactive--forming dimers, and, ultimately, melanin-like polymeric products. A model compound, leading to more stable metabolites, can be obtained by introduction of methyl groups next to the oxygen, to produce 3,5-dimethylacetaminophen. The electron spin resonance spectrum of this free radical could be completely analyzed. The phenoxyl radical of the dimethyl analog does not form polymers or bind with nucleophiles. N-Acetyl-p-benzoquinone imine, a hepatic metabolite of acetaminophen, and its analog N-acetyl-3,5-dimethyl-p-benzoquinone imine are metabolized by rat liver microsomes and NADPH to their corresponding p-aminophenoxyl free radicals. The p-aminophenoxyl free radical formation could be suppressed by the deacetylase inhibitors sodium fluoride and paraoxon. Substitution of NADPH-cytochrome P-450 reductase for rat liver microsomes eliminates the deacetylase activity and results in the direct reduction of N-acetyl-3,5-dimethyl-p-benzoquinone imine to the 3,5-dimethylacetaminophen phenoxyl free radical. Neither the acetaminophen nor the 3,5-dimethylacetaminophen phenoxyl radical reduces oxygen to form superoxide or reacts with oxygen in any other detectable way.

Acetaminophen↗
PubMed1985

Formation of 4-aminophenoxyl free radical from the acetaminophen metabolite N-acetyl-p-benzoquinone imine.

N-Acetyl-p-benzoquinone imine, a hepatic metabolite of acetaminophen, and its analogue, N-acetyl-3,5-dimethyl-p-benzoquinone imine, were metabolized by rat liver microsomes and NADPH to their corresponding 4-aminophenoxyl free radicals. ESR spectra were recorded and unambiguously identified. As indicated by the purple color and confirmed by UV and mass spectroscopy, indophenols were formed as final products. The 4-aminophenoxyl free radical formation could be suppressed by the deacetylase inhibitors, sodium fluoride and paraoxon. Microsomal incubations of N-acetyl-2,6-dimethyl-p-benzoquinone imine and NADPH do not result in a detectable radical concentration; in addition, no indophenol was found. Substitution of NADPH-cytochrome P-450 reductase for rat liver microsomes eliminates the deacetylase activity and results in direct reduction of N-acetyl-3,5-dimethyl-p-benzoquinone imine to the N-acetyl-2,6-dimethyl-4-aminophenoxyl free radical. Neither the incubation of N-acetyl-p-benzoquinone imine nor that of N-acetyl-2,6-dimethyl-p-benzoquinone imine with NADPH-cytochrome P-450 reductase yielded a detectable concentration of the corresponding phenoxyl free radical. When starting material that had been exposed to the atmosphere was used, a previously reported free radical with a splitting constant of approximately 2 G was formed. This spectrum is identical with that of the 2,6-dimethyl-p-benzosemiquinone free radical, implying hydrolysis of the starting material. Neither the N-acetyl-4-aminophenoxyl nor the N-acetyl-2,6-dimethyl-4-aminophenoxyl radical reduces oxygen to form superoxide or react with oxygen in any other detectable way.

Animals↗
PubMed1985

Free-radical metabolites of acetaminophen and a dimethylated derivative.

The oxidation of acetaminophen (4'-hydroxyacetanilide) to the corresponding N-acetyl-p-benzoquinone imines by plant and mammalian peroxidases is discussed. The acetaminophen free radical (N-acetyl-4-aminophenoxyl) has been reported as an intermediate. It is very reactive and forms melanin-like polymeric products. Application of a fast-flow system makes it possible to detect the transient species and clearly distinguish it from persistent paramagnetic melanin polymers. A model system, leading to more stable metabolites, can be obtained by introduction of methyl groups next to the oxygen, 3',5'-dimethylacetaminophen (3',5'-dimethyl-4'-hydroxyacetanilide). The ESR spectrum of the free radical formed could be completely analyzed and confirmed by deuterium substitution. The data are consistent with the assignment to a phenoxyl free radical (N-acetyl-2,6-dimethyl-4-amino-phenoxyl). Its formation is discussed in terms of substrate, hydrogen peroxide and enzyme concentration dependence. It is believed to be formed via a direct one-electron oxidation of 3',5'-dimethyl-4'-hydroxy-acetanilide. The radical does not form polymers or react with nucleophiles. Its redox behavior is discussed. The possible reaction of these phenoxyl free radicals with oxygen is thought to be negligible.

Acetaminophen↗
PubMed1984

Stable free radical and benzoquinone imine metabolites of an acetaminophen analogue.

The enzymatic oxidation of the acetaminophen analogue 3',5'-dimethyl-4'-hydroxyacetanilide (3',5'-dimethylacetaminophen) with the horseradish peroxidase/hydrogen peroxide system forms a phenoxyl free radical metabolite. The structure of this free radical is established by a complete analysis of the ESR spectrum and confirmed by deuterium isotope substitution. Concomitant with phenoxyl radical formation, N-acetyl-3,5-dimethyl-p-benzoquinone imine was detected by optical spectroscopy. The free radical is also formed by comproportionation in solutions of the quinone imine containing added 3',5'-dimethylacetaminophen. In contrast to acetaminophen, the imine and radical metabolites are stable and can be detected without resort to rapid-mixing techniques. Factors leading to the increased stability of these metabolites relative to those formed from acetaminophen are discussed in terms of the toxicity of acetaminophen.

Acetaminophen↗
PubMed1980

Positive histological tuberculous findings despite stable sterility of the urine on culture: results of 111 nephrectomies and partial nephrectomies.

The therapy of genitourinary tuberculosis has changed: 'néphrectomie nécessaire' has been replaced by 'néphrectomie opportune'. Today, it is generally assumed that tuberculosis can be cured completely by chemotherapy. The following question must, however, be asked: How far may the stable sterility of the urine be considered as a complete cure? In order to assess the efficiency of chemotherapy as a function of time and dosage, the activity of tuberculosis of the kidneys was investigated on the basis of the histological preparation, after removal of the tuberculous renal tissue. Despite stable sterilization of the urine, 15% of the cases showed active tuberculosis. Using the triple therapy combination of rifampicin, ethambutol and isoniazid, the disease was found no longer to be active after 2--3 months of treatment in 90% of the cases. A longer period of treatment brought no further improvement.

Capreomycin↗
PubMed1978

[Etiological assessment of aseptic femoral head necrosis from blood serum metabolic parameters (author's transl)].

The etiological assessment of aseptic femoral head necrosis in adults is facilitated by investigation of the uric acid level and of fat metabolism parameters. From 98 of our own patients it appears that femoral head necrosis after trauma, irradiation therapy and caisson disease and after massive doses of cortisone only exceptionally shows pathological serum levels. Femoral head necrosis with manifest metabolic diseases shows 53.3% hyperuricemias and hyperlipemias or dyslipidemias. Of femoral head necroses without concomitant diseases, prior physical effects and administration of cortisone, 91% had hyperuricemia and 65% hyperlipemia or dyslipidemia.

Adult↗
PubMed1977

[Muscular absorption of low frequency resonance in animal experiments (author's transl)].

For the further clarification of helicopter pilot's spinal troubles caused by vibration the muscular absorption was examined with the help of animal experiments. On a swinging-table acceleration values were measured in Pirbright cavies; at first this was done under a defence reaction of the muscles, and in second experiment under maximum muscular relaxation. In the tense animal the resonance occurring at 5 Hz was almost completely absorbed, whereas in the relaxed animal a clear resonance--curve could be developed at 5 Hz. On the other hand vibration at a higher frequency up to 15 Hz were to an increasing extent better absorbed in the relaxed animal than in animal with a muscular defence reaction. For this reason the protective function of a not fatigued musculature for the defence of especially badly tolerated resonance vibrations is being discussed.

Animals↗