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Biomedical subjects

S A Rice

Publications and source records attributed to S A Rice.

At least 109 records · Page 6Linked to original sources

Fluroxene mutagenicity.

The commercially available volatile anesthetic fluroxene (2,2,2-trifluoroethyl vinyl ether) which contains the stabilizer N-phenyl-1-napthylamine, was tested for mutagenicity using four strains of S. typhimurium, TA1535, TA1537, TA98 and TA100, and one strain of E. coli, WP2. In addition, purified fluroxene; N-phenyl-1-napthylamine; trifluoroethanol, a major metabolite of fluoroxene; and urine from rats anesthetized with fluroxene were tested. Several procedures were utilized including exposure of bacteria to vapor in desiccators and in liquid suspension. Results indicate that fluroxene, but not its stabilizer, was mutagenic to strains TA1535, TA100 and WP2 only in liquid suspension and only in the presence of a rat-liver enzyme system. Trifluoroethanol and urine from fluroxene-treated rat were not mutagenic to any strain of bacteria. These findings indicate that fluroxene is a promutagen which requires preincubation before it is recognized. Further experiments were performed with enzymes prepared from mouse, hamster and human liver. Fluroxene was mutagenic only in the presence of enzymes prepared from Aroclor 1254 pretreated rodents. Since fluroxene was not mutagenic in the presence of enzymes prepared from three human livers, the significance of these findings to man are unclear.

Animals↗

The effects of heparin pretreatment on plasma histamine following thermal injury in rats and cats.

An elevated plasma histamine level in response to thermal injury is demonstrated in the rat and cat. In cats, the initial elevation of plasma histamine occurred within the first 15 minutes following thermal injury, and this was followed by a second rise between 60 and 120 minutes. Heparin pretreatment markedly reduced the plasma histamine elevating effect of thermal injury in both rats and cats. This suggests that the therapeutic basis for the use of heparin in the treatment of burn shock might conceivable be attributed to its ability to interfere with the elevated histamine levels normally associated with thermal injury.

Animals↗

Effects of pretreatment with anti-inflammatory drugs on ozone-induced lung damage in rats.

The effects of pretreatment with acetylsalicylic acid (aspirin), hydrocortisone, indomethacin, and heparin administered ip against the pulmonary edema produced by O3-exposure (4 ppm for 4 hr) were studied in rats. These anti-inflammatory drugs were found to alter the injurious effect of O3 on lung differently. First, aspirin at the high dose (125 mg/kg) accentuated O3-induced lung injury, and had no effect at the low dose (10 mg/kg); second, hydrocortisone (50 mg/kg) failed to have any effect; third, indomethacin at a high dose (20 mg/kg) offered a significant degree of protection, but had no effect at the low dose (2.5 mg/kg); and fourth, heparin (1000 units/kg) also offered a significant degree of protection against the lung damage normally induced by O3-exposure. Several mechanisms for the favorable and unfavorable interactions of anti-inflammatory drugs with O3-exposure are discussed.

Animals↗

Preparation of amorphous solid water.

A method of preparation of solid amorphous water is reported, along with a demonstration of the absence of crystalline ice. The samples described are the first to be completely free of contamination with crystalline ice.

Journal Article↗

Model for constraint and control in biochemical networks.

A model is proposed for biochemical networks which takes into account substrate and modifier effects on enzyme activity and the different time scales on which the relevant processes occur. Sources of global constraint that can be utilized in metabolic regulation are indicated, and the relation of the model to the experiments of Kauffman on switching networks is analyzed. The biological significance of the model and possible systems in which it might be tested are discussed.

Cybernetics↗

The stability theory of nonpolynomial kinetics.

The results of an investigation of the formal stability behavior of equivalent classes of kinetic equations (generated by stability constraint specifications) that are general enough to include nonpolynomial kinetics are outlined. The immediate motivation for the study arose from the need for a comprehensive theory when steric interactions in biosynthetic networks are explicitly taken into account.

Catalysis↗

In vitro hepatic drug and anesthetic metabolism of rats with dietary-induced obesity.

The mechanism for enhanced metabolism of inhaled anesthetics in obese rats and humans is unknown. In this study, hepatic microsomes from normal-weight chow-fed rats and rats fed a high fat diet for approximately 54 weeks to induce obesity were examined for their ability to metabolize fluorinated inhalation anesthetics. Body composition of rats on diet for 54 weeks revealed a significantly elevated lipid content of both the whole body and liver in obese compared to normal-weight rats. Protein per g liver was not significantly different. The hepatic microsomal content of cytochromes b5 and P-450 per mg protein was not different between obese and normal-weight rats. Hepatic microsomal defluorination rates of the anesthetics, methoxyflurane, enflurane and isoflurane, were not altered by high fat diets of 54 weeks duration. The activity rate of aminopyrine N-demethylase was not changed by the diet; however, p-nitroanisole O-demethylase activity was significantly increased in microsomes from obese rats to approximately 150% of control activity. Thus the enhanced in vivo anesthetic metabolism of obese Fischer 344 rats does not appear to be the result of an increase in the specific activity of anesthetic metabolizing enzymes.

Anesthetics↗

Purification and identification of rat hepatic cytosolic enzymes responsible for defluorination of methoxyflurane and fluoroacetate.

Enzymes responsible for the defluorination of methoxyflurane (MOF) and fluoroacetate (FAc) were separated and purified from rat liver cytosol. Both hepatic cytosolic enzymes with defluorination activity were labile and addition of 2-mercaptoethanol had little effect on the stability of these enzymes. Glutathione S-transferase (GT) activity of the same cytosolic fractions was stable for at least 11 days. Separation of defluorination and GT enzymatic activities on DEAE-Sephadex A-50 and reduced glutathione-affinity columns revealed that the defluorinations of MOF and FAc were primarily catalyzed by anionic proteins which also exhibited GT activity. Further identification by two-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed protein bands with pl values of approximately 6.5 and 6.9 and molecular weights of approximately 20,000. However, other proteins that exhibited no GT activity also defluorinated MOF and FAc, but accounted for only 10% of the total defluorination activity present in anionic proteins. Results from a separate purification experiment using a CM-cellulose column also indicated that the enzymes responsible for defluorination coeluted with cationic GTs. Collectively, these cationic enzymes were responsible for about 20% of the recovered cytosolic defluorination activities. The results suggest that the cytosolic defluorinations of both MOF and FAc are primarily the result of a dehalogenation reaction catalyzed by one or more species of rat liver cytosolic GTs.

Animals↗

Effects of subchronic intermittent exposure to isoflurane in Swiss Webster mice.

Swiss Webster mice were treated to determine if subchronic intermittent exposure to the inhalation anesthetic isoflurane causes organ toxicity or enhances its own metabolism or that of other anesthetics. One-hundred twenty, four-week-old male and female mice were exposed to compressed air or to 0.02%, 0.1% or 0.5% of isoflurane for four hours per day, five days per week for nine weeks. Body weights among the groups were the same prior to exposure. Overall, there were no significant differences in body weights among exposure groups (ANOVA with day as a repeated measure: females - F = 2.12, P = 0.1085; males - F = 1.80, P = 0.1583). There was, however, a significant interaction of group and days; differences were isolated to the start of exposure (weeks 1 through 3 for females; week 2 for males). At all times, differences remained within 10% of the control body weights. Organ weights (liver, spleen, kidney, testis and uterus), hematocrits, and SGOT levels were similar among exposure groups. Histologic evaluation of organs revealed no anesthetic-related organ toxicity. The concentration of hepatic cytochromes, b5 and P-450, per mg of microsomal protein were similar among exposure groups and between sexes. The rates of hepatic microsomal metabolism (defluorination) of three volatile halogenated ether anesthetics (methoxyflurane, enflurane, and isoflurane) were not different among groups following nine weeks of exposure. Isoflurane exposures of 0.5% or less for four hours per day for five days per week would appear to be the maximum tolerated concentration for any chronic study. Since there was no evidence of organ toxicity or of enhanced or inhibited hepatic microsomal enzyme activity, isoflurane seems to be relatively non-toxic inhalation anesthetic under the conditions of this study.

Animals↗