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Biomedical subjects

R A Floyd

Publications and source records attributed to R A Floyd.

At least 163 records · Page 9Linked to original sources
PubMed1978

Spin-trapping of the trichloromethyl radical produced during enzymic NADPH oxidation in the presence of carbon tetrachloride or bromotrichloromethane.

Utilizing the spin-trapping agent phenyl-t-butyl nitrone, a free radical has been detected which is produced from carbon tetrachloride or bromotrichloromethane during the enzymic oxidation of NADPH by rat liver microsomes. The presence of NADPH is obligatory for generation of the radical. The formation of the trichloromethyl radical-phenyl-t-butyl nitrone adduct is an enzymic process, as evidenced by the inhibition of its formation in systems containing heated microsomes and in systems containing p-hydroxymercuribenzoate. A computer-simulated ESR spectrum for the trichloromethyl adduct of phenyl-t-butyl nitrone can reproduce the essential features of the spectrum of the spin-trapped radical produced enzymically from CCl4. A mechanism is proposed for the formation of the trichloromethyl radical from CCl4 or BrCCl3.

Animals↗
PubMed1978

Activation of the carcinogen N-hydroxy-2-acetylaminofluorene by rat mammary peroxidase.

A peroxidase preparation from rat mammary gland parenchymal cells, a target tissue of arylamine carcinogens, was shown to activate the carcinogen N-hydroxy-2-acetylaminofluorene via a nitroxyl free radical intermediate to the more active carcinogens nitrosofluorene and N-acetoxy-2-acetylaminofluorene. Hydrogen peroxide, cumene hydroperoxide, and linoleic acid hydroperoxide were effective as substrates. The antioxidants ascorbate, propyl gallate and reduced glutathione prevented the free radical activation route.

Animals↗
PubMed1977

Obligatory free radical intermediate in the oxidative activation of the carcinogen N-hydroxy-2-acetylaminofluorene.

We have demonstrated that the nitroxyl free radical form of the carcinogen N-hydroxy-2-acetylaminofluorene (OH-AAF) is an obligatory intermediate in the cumene hydroperoxide-hematin-induced oxidative activation of this carcinogen into 2-nitrosofluorene and N-acetoxy-2-acetylaminofluorene. Both the rate of N-OH-acetylaminofluorene oxidation and the amount of its nitroxyl free radical were experimentally observed as a function of reaction time. Rate equations were derived for a model in which the nitroxyl free radical form of OH-AAF was an obligatory intermediate in the reaction. Using this theory it was possible to compute one experimental variable, the rate of OH-AAF oxidation, utilizing the other experimental variable, the amount of nitroxyl free radical present at any time during the reaction. The theory also predicts a linear relationship between the rate of OH-AAF oxidation and the square of the free radical content; and this was found to be true experimentally. The dismutation rate constant of the nitroxyl free radical of OH-AAF was found to be 2.7-10(5) M-1-s-1.

Fluorenes↗
PubMed1977

Pharmacokinetics in drug therapy II: Applications of clinical pharmacokinetics in the assessment of theophylline therapy.

A patient case is presented to illustrate a systematic approach to the assessment and modification of theophylline therapy by the pharmacist using serum level analysis. The pharmacist is a pulmonary disease service is responsible for: (1) determining relevant aspects of the patient's clinical condition; (2) defining an initial theophylline administration regimen, including route, dose and schedule; (3) estimating expected theophylline levels based upon the regimen and known or assumed parameters of theophylline in the patient; (4) defining and recommending number and timing of serum samples to be drawn for analysis; (5) obtaining laboratory results and comparing with preliminary estimations; (6) assessing clinical response or toxicity, or both; and (7) recommending appropriate modifications in the theophylline regimen.

Administration, Oral↗
PubMed1976

Horseradish peroxidase/hydrogen peroxide-catalyzed oxidation of the carcinogen N-hydroxy-N-acetyl-2-aminofluorene as effected by cyanide and ascorbate.

Horseradish peroxidase and H2O2 mediate N-hydroxy-N-acetyl-2-aminofluorene (N-OH-AAF) conversion into two more potent carcinogens, 2-nitrosofluorene and N-acetoxy-N-acetyl-2-aminofluorene. Optical studies of this system indicate that horseradish peroxidase is operating as a peroxidase with N-OH-AAF as the electron donor. Our studies confirm the earlier finding that 2-nitrosofluorene and N-acetoxy-N-acetyl-2-aminofluorene are the products of the type II enzyme-mediated oxidation of N-OH-AAF, but surprisingly, the results with the type VI enzyme indicate that more 2-nitrosofluorene was formed and, in addition, another product absorbing at 245 nm was formed. If ascorbate is present in the N-OH-AAF/horseradish peroxidase/H2O2 system, ascorbate is oxidized preferentially. Cyanide, a known inhibitor of the peroxidase, does not inhibit when N-OH-AAF is the electron donor. The reaction products are the same in the presence or absence of cyanide.

Acetoxyacetylaminofluorene↗
PubMed1976

Lipid hydroperoxide activation of N-hydroxy-N-acetylaminofluorene via a free radical route.

The data presented here demonstrate that linoleic acid hydroperoxide in the presence of methemoglobin or hematin activated the carcinogen N-hydroxy-N-acetyl-2-amino-fluorene via the nitroxyl free radical intermediate into 2-nitrosofluorene and N-acetoxy-N-acetyl-2-aminofluorene. Ascorbate inhibited the activation, in which case the free radical intermediate was replaced by the ascorbate free radical. On the basis of optical kinetics, we have established that the rate of linoleic acid hydroperoxide decrease paraleled the rate of N-hydroxy-N-acetyl-2-aminofluorene decrease and also the rate of 2-nitrosofluorene increase. The stoichiometry of the reaction was such that, for every 2 linoleic acid hydroperoxide molecules consumed, 2 N-hydroxy-N-acetyl-2-aminofluorene molecules were oxidized and 1 2-nitrosofluorene and 1 N-acetoxy-N-acetyl-2 aminofluorene molecule was formed.

Ascorbic Acid↗
PubMed1975

Changes of tissue water proton relaxation rates during early phases of chemical carcinogenesis.

Water proton spin lattice relaxation rate (T1) was determined on tissues of rats experiencing early phases of chemical carcinogenesis. Rats were fed a fast acting carcinogen, 3'-methyldimethylaminoazobenzene, and a slower acting carcinogen, 2-acetylaminofluorene, for up to 4 weeks. T1 of blood serum and liver tissue was significantly higher than those of controls after 4 weeks of 3'-methyldimethylaminoazobenzene feeding. This was not the case for 2-acetylaminofluorene. The blood serum T1 increase reflected the onset of liver nodulation (assumed to be preneoplastic). Liver T1 values increased as the degree of nodulation increased. Blood serum T1 correlated inversely with protein content and directly with water content. Liver T1 values correlated with water content, but this was not true for spleen T1 values. Spleen T1 values were significantly lower than controls at the earliest sampling date for each carcinogen: one week for 3'-methyldimethylaminoazobenzene and 4 weeks for 2-acetylaminofluorene. The spleen T1 decrease paralleled an increase of iron detectable by electron spin resonance in this tissue. Spleen T1 decreases are probably not unique to chemical carcinogenesis.

Animals↗