Higher Percentage Of Radioactivity Research Articles

Differences in the metabolism and pharmacokinetics of two structurally similar PPAR agonists in dogs: involvement of taurine conjugation

The metabolism and pharmacokinetics of two structurally similar PPAR agonists, MRL-I, (2R)-7-[3-[2-chloro-4-(4-fluorophenoxy)phenoxy]propoxy]-2-ethyl-3,4-dihydro-2H-benzopyran-2-carboxylic acid, and MRL-II, (2R)-7-[3-[2-chloro-4-(2,2,2,-trifluoroethoxy)phenoxy]propoxy]-3,4-dihydro-2-methyl-2H-benzopyran-2-carboxylic acid, in dogs were investigated.MRL-I was absorbed rapidly in dogs and exhibited linear pharmacokinetics over the dose range examined, 1–25 mg kg−1. In contrast, the pharmacokinetics of MRL-II were non-linear following both intravenous and oral administration.The acyl glucuronide (AG) conjugate was the only radioactive component detected in bile from dogs dosed with [14C]MRL-I, whereas bile from dogs dosed with [14C]MRL-II contained varying amounts of both the AG and taurine conjugates. The percentages of the acyl glucuronide and taurine conjugates of [14C]MRL-II in dog bile were dose dependent. A higher percentage of radioactivity was associated with the taurine conjugate (about 41%) following intravenous administration at 0.2 mg kg−1 than at 0.9 mg kg−1 (about 14%) or oral administration at 5 mg kg−1 (about 6%). The decrease in the percentage of radioactivity associated with the taurine conjugate at 0.9 mg kg−1 was accompanied by a concomitant increase in the amount of the acyl glucuronide.MRL-I, but not MRL-II, was subject to significant enterohepatic recirculation in dogs. Continuous collection of bile resulted in an 11-fold decrease in the terminal half-life of MRL-I in plasma (1.5 versus 16.6 h), and a 2.4-fold increase in its plasma clearance (4.0 versus 1.7 ml min−1 kg−1) after intravenous administration at 1 mg kg−1.Collectively, the data suggest that the presence and subsequent saturation of the taurine conjugation pathway might have contributed to the non-linear pharmacokinetics of MRL-II in the dog.

Radionuclide transport from soil to air, native vegetation, kangaroo rats and grazing cattle on the Nevada test site.

Between 1970 and 1986 the Nevada Applied Ecology Group (NAEG), U.S. Department of Energy, conducted environmental radionuclide studies at weapons-testing sites on or adjacent to the Nevada Test Site. In this paper, NAEG studies conducted at two nuclear (fission) sites (NS201, NS219) and two nonnuclear (nonfission) sites (Area 13 [Project 57] and Clean Slate 2) are reviewed, synthesized and compared regarding (1) soil particle-size distribution and physical-chemical characteristics of 239 + 240Pu-bearing radioactive particles, (2) 239 + 240Pu resuspension rates and (3) transuranic and fission-product radionuclide transfers from soil to native vegetation, kangaroo rats and grazing cattle. The data indicate that transuranic radionuclides were transferred more readily on the average from soil to air, the external surfaces of native vegetation and to tissues of kangaroo rats at Area 13 than at NS201 or NS219. The 239 + 240Pu resuspension factor for undisturbed soil at Area 13 was three to four orders-of-magnitude larger than at NS201 and NS219, the geometric mean (GM) vegetation-over-soil 239 + 240Pu concentration ratio was from ten to 100 times larger than at NS201, and the GM GI-over-soil, carcass-over-soil and pelt-over-soil 239 + 240Pu ratios for kangaroo rats were about ten times larger than at NS201. These results are consistent with the finding that Area 13, compared with NS201 or NS219, has a higher percentage of radioactivity associated with smaller soil particles and a larger percentage of resuspendable and respirable soil. However, the resuspension factor increased by a factor of 27 at NS201 when the surface soil was disturbed, and by a factor of 12 at NS219 following a wildfire. The average (GM) concentration of 239 + 240Pu for the GI (and contents) of Area 13 kangaroo rats and for the rumen contents of beef cattle that grazed Area 13 were very similar (400 vs. 440 Bq kg-1 dry wt, respectively) although the variability between individuals was very large. The GM carcass-over-GI 239 + 240Pu concentration ratio for kangaroo rats at Area 13, Clean Slate 2, and NS201 were similar in value (approximately 2 X 10(-2)), as were the GM GI-over-vegetation concentration ratios (approximately 2 X 10(0)) (no statistical differences).(ABSTRACT TRUNCATED AT 400 WORDS)

Biosynthesis of wax in the honeybee, Apis mellifera L.

The composition of the cuticular wax of the honeybee is quantitatively different from that of the comb wax. The major component of the cuticular lipids is hydrocarbon, which comprises 58% of this wax. In contrast, hydrocarbon comprises only 13–17% of the comb wax, and monoester is the largest component ( Tulloch 1971). The major fractions of the cuticular wax were analyzed by gas-liquid chromatography, and were shown to be qualitatively similar to those of the comb wax. The incorporation of injected radio-labelled acetate into hexane extractable wax by worker honeybees not actively producing comb wax resulted in the recovery of much of the radioactivity in the hydrocarbon fraction. In insects actively producing comb wax, a higher percentage of radioactivity was recovered in the monoester fraction. A dramatic effect of age on the distribution of radioactivity from acetate into the various wax fractions from honeybees studied in the summer months was observed. In insects from eleven to eighteen days following emergence to adults, the major wax component synthesized was monoester, whereas in younger and older insects, hydrocarbon was the major wax component formed. Both in vivo and in vitro experiments using insects actively producing comb wax showed that the abdomen produced significant amounts of monoester, hydrocarbon, and other esters, whereas the thorax synthesized mostly hydrocarbon. These data show that the epidermal cells and wax glands each produce a wax with a distinct composition, and that the age and seasonal differences observed in wax synthesis are due to the presence or absence of active wax glands.

Uptake and metabolism of 3H-estrone in neural and peripheral tissue of gonadectomized adult and neonatal guinea pigs

(1) Adult and neonatal male and female guinea pigs were gonadectomized, injected with 3H-estrone (40 μCi/animal) and killed 4 hr after injection. (2) All neural tissues studied (hypothalamus, amygdala, septal area, and cerebral cortex) retained significantly more radioactivity than plasma. (3) Almost all radioactivity was recovered as either estrone or estradiol-17β. (4) A greater percentage of the total radioactivity in the hypothalamus was recovered as estradiol-17β than in other brain tissues. (5) Males and females were similar in their uptake patterns. (6) Neonatal animals generally did not selectively retain tritiated estrogen in neural tissues, though their absolute values of radioactivity were higher than adults. (7) Peripheral tissues (uterus, seminal vesicles) were the only tissues in which a higher percentage of radioactivity was recovered as estradiol-17β than as estrone. (8) Results are discussed in terms of the hypothesis that estrone must be converted to estradiol-17β for it to facilitate lordosis behavior.

Effects of hypo- and hyper-thyroidism on in vivo lipogenesis in fed and fasted rats.

Thyroidectomized rats (T) daily injected with either 0, 0.1, 1.8 or 25 microgram of L-thyroxine/100 g body wt. were compared with intact controls (C). The appearance of radioactivity in fatty acids 30 min after the i.p. injection of (3-14C)pyruvate was reduced in adipose tissue and enhanced in liver of T+25, being no differences between the other groups and C. (14C)-Fatty acids are reduced with 3 h of fasting only in the adipose tissue of T+1.8 and C, while 24 h produces a reduction in liver in the T+1.8, T+25 and C, and in adipose tissue in the T+1.8 and C animals. The highest percentage of radioactivity was observed in the liver glyceride glycerol fraction, being greater in T+25 than in the other groups. Fasting produces an increment in the (14C)-glyceride glycerol fraction. Being significant only in thehypothyroid animals in both liver and adipose tissue. The most sensitive parameter to fasting was the formation of (14C)-non-saponifiable lipid in both the C and T+1.8 animals, while it does not change in T+0 or T+0.1, but is enhanced within 24 h in the adipose tissue of T+25. It is proposed that most of the observed changes are due to the other endocrine disfunction s which appear in hypo- and hyperthyroidism, as the in vivo results do not comply with in vitro effects of thyroxine onlipogenesis of others.

A study of methods of incorporation and source of14C on distribution of radioactivity in potato plants

Russet Burbank potato plants grown in the greenhouse were given14C as14CO2 and as uniformly labelled sucrose. Labelled sucrose was applied; (1) by injection into the main stem, (2) injection with a hypodermic needle into the debladed petiole and (3) uptake of labelled sucrose kept in a vial fastened to the main stem using thread as a wick. Plants harvested 6 hours later were analyzed for radioactivity in the foliage, roots, and tubers. The greatest proportion of radioactivity was found in the foliage. Tubers were analyzed for radioactivity in the basic (amino acids), acidic (organic acids and sugar phosphates), neutral (sugars) and alcohol insoluble solid (starch) fractions. Most of the radioactivity was found in the sugar component of the chemical fraction. Plants treated with147CO2 had a higher percentage of radioactivity in the acidic and starch fractions than plants treated with sucrose. Sucrose applied by petiole injection not only showed higher total incorporation but also exhibited more translocation of labelled material into the tubers than the other methods.

Lipids of cultured hepatoma cells: VIII. Utilization of D‐[1‐14C] glucose for lipid biosynthesis

Minimal deviation hepatoma 7288C cells (HTC) were incubated in serum-supplemented and serum-free Swim's 77 medium in the presence of D-[1-14C] glucose for 1, 2, 4, 8, 12 and 24 hr. Glucose oxidation to CO2, incorporation into total cell mass, and incorporation into cell and medium lipids were determined. The percentage distribution of total cell lipid radioactivity in individual neutral and polar lipid classes was followed as a function of time. Degradation studies of individual lipid classes were performed to ascertain the percentage of radioactivity in acyl and glycerol moieties. The percentage of D-[1-14C] glucose oxidized to 14CO2, incorporated into cell matter and cell lipids was elevated in cells incubated in serum-free medium as opposed to serum-supplemented medium. The percentage distribution of total cell lipid radioactivity into individual neutral lipid classes from both serum-free and serum-supplemented cultures was as follows: sterols greater than triglycerides greater than free fatty acids greater than sterol esters. The percentage distribution of total cell lipid radioactivity into individual polar lipid classes of serum-supplemented cultures was as follows: phosphatidylcholine greater than phosphatidylinositol greater than sphingomyelin greater than phosphatidylethanolamine greater than phosphatidylserine. The distribution of glucose radiolabel into individual polar lipid classes of serum-free HTC cells was different from their serum-supplemented counterparts: sphingomyelin greater than phosphatidylcholine greater than phosphatidylinositol greater than phosphatidylethanolamine greater than phosphatidylserine. Glycerol from glyceride classes contained a higher percentage of radioactivity than the acyl moieties, with this percentage significantly elevated in serum-free cultures. The data indicate that, although glucose is a substrate for HTC cell lipids, other precursors present in the culture system also contribute to the lipid constituency of this hepatoma cell line.

Metabolism of Na275SeO4inAstragalus bisulcatusLima Bean, and Wheat: a Comparative Study

A comparative study of the metabolism of Na2 75Se04 in Astragalus bisulcatus, lima bean, and wheat has been carried out. The results indicate that all three plants metabolize selenium extensively. Important differences were observed in the distribution of radioactivity between the various fractions isolated from the plants. Compared to the protein fraction, the free amino acid fraction from A. bisulcatus contained a higher percentage of radioactivity. The converse was true for wheat and lima bean. As A. bisulcatus proteins contained a significant percentage of radioactivity, it is suggested, that the differences in the toxicity of selenium towards wheat, lime bean, and A. bisulcatus are difficult to explain in terms of the differences in its incorporation into the protein of the three speoies.