Disposition of (1,2-14C) vinyl chloride in the rat

Morphological and physiological studies were carried out on Caiman crocodilus under experimentally produced metabolic changes. During N2-respiration the cochlear potentials responded differently. The negative component (CM-) of the cochlear microphonics decreased continuously, whereas the CM+ component showed only a little change. The summation action potential (AP) exhibited a similar behaviour to that of CM-. These alterations were reversible up to periods of 30 min N2-respiration. The morphological findings, after N2-respiration, showed an intracellular oedema of the hair cells. The afferent synaptic contacts are always recognizable. Different degrees of disintegration within the presynaptic structures were seen. Efferent axosomal and axodendritic synapses were unchanged. MIA-perfusion led to an irreversible decrease of the cochlear potentials (CM+; CM-; AP) and morphologically to a total destruction of the papilla basilaris. The changes in the presynaptic structures during anaerobic metabolism offer the possibility of a new explanation for the reversibility of sudden deafness.     

Metabolism of testosterone 4-14C in skin of castrated rats

The modifications produced by 6-hydroxydopamine (6-OHDA) on the analgesic and toxic effects of morphine have been studied in mice and cats. After intracerebral injections of 6-OHDA, mice had a lower threshold for morphine-induced convulsions. Morphine analgesia assayed by the phenylquinone test was apparently antagonized in the 6-OHDA pretreated mice, but the 6-OHDA mice showed more reactivity to the phenylquinone. Intraventricular injection of 6-OHDA in cats produced an acute syndrome with mydriasis, bradycardia, bradypnea, hypothermia and EEG slowing, which subsided after several days, 6-OHDA was successful in blocking the morphine mania, but the animals died within 24 h.     

Metabolism of [1-(14)C] and [2-(14)C] leucine in cultured skin fibroblasts from patients with isovaleric acidemia. Characterization of metabolic defects

Leucine metabolism in cultured skin fibroblasts from patients with isovaleric acidemia was compared with that in normal fibroblasts and in cells from patients with maple syrup urine disease using [1-(14)C] and [2-(14)C] leucine as substrates. Inhibitory effects of methylenecyclopropylacetic acid on leucine metabolism in normal cells were also investigated. Production of 14CO2 from [2-(14)C] leucine was very reduced (96-99%) in both types of mutant cells. Radioactive isovaleric acid accumulated in assay media with isovaleric acidemia cells but not in those with maple syrup urine disease cells. Unexpectedly, 14CO2 production from [1-(14)C] leucine was partially depressed (80%) in isovaleric acidemia cells whereas in maple syrup urine disease cells it was strongly depressed (99%) as expected. These two mutant cells were clearly distinguished by detection of 14C-isovaleric acid accumulation after incubation with [2-(14)C] leucine. A pattern of inhibition of leucine oxidation similar to that seen in isovaleric acidemia cells was induced in normal cells by the addition of 0.7 mM methylenecyclopropylacetic acid to the assay medium. The partial inhibition of [1-(14)C] leucine oxidation seen in isovaleric acidemia cells and also in normal cells in the presence of the inhibitor appears to be, at least in part, due to an accumulation of isovalerate in the cells. Isovaleric acid (5-10) mM) inhibited [1-(14)C] leucine oxidation 32-68% when added to the assay medium with normal cells. Addition of flavin adenine dinucleoside to culture medium or assay medium or both did not restore oxidation of either leucine substrate in isovaleric acidemia cells.     

Estimation of tissue protein synthesis in rats fed diets labeled with (U-14C)tyrosine

The rate of liver and muscle protein synthesis has been measured in 27 rats after feeding L-[U-14C]tyrosine in L-amino acid diets prepared as agar gels. Constant specific activity of the free tyrosine pool, as indicated by constant excretion of 14CO2, was reached within 2 h of feeding and was maintained for the remaining 6 h of the 8-h experiment. Muscle protein synthesis was decreased (P less than 0.05) in rats fed a 0.3% methionine diet compared with rats fed this diet supplemented with 0.51% cystine (fractional rate of synthesis, ks: 0.098 vs. 0.121). No effect (P greater than 0.05) of these diets on liver protein synthesis was observed (ks: 0.603 vs. 0.532). Protein synthetic rate was also determined by the constant-intravenous infusion technique in 17 rats fed unlabeled diets. The two techniques gave similar estimates. Restraint of the rats or the infusion of saline had no measurable effect on the rate of protein synthesis in rats fed labeled diets. This feeding technique is essentially equivalent to the constant-infusion technique and offers an easier, more physiological approach to achieving a steady state.     

Synthesis of 1,2-dioleoyl-3-(alpha-14C-1-adamantoyl)-sn-glycerol and 1-14C-adamantanecarboxylic acid

The pancreatic lipase inhibitor 1,2-dioleoyl-3-(alpha-14C-1-adamantoyl)-sn-glycerol, with a specific activity of 8 mCi/mmole, was prepared by consecutive acylation of 1,2-isopropylidene-sn-glycerol with 1-14C-adamantanecarboxylic acid chloride and oleoyl chloride. The 14C-labeled acid was conveniently prepared by carboxylation of 1-adamantanol using 14C-sodium formate in concentrated sulfuric acid.     

Incorporation of (1-14C)oleic acid and (1-14C)arachidonic acid into lipids in the subcellular fractions of mouse brain

The response of the astroglial population of the dentate gyrus molecular layer to removal of that region's primary afferent was investigated using Cajal's gold sublimate method. Deafferentation caused the astrocytes to hypertrophy, an effect which was detectable at 24 hr and maximal at 72-96 hr post-lesion. Following this, the astroglia entered a lengthy period of gradual atrophy. Counts of the astrocytes in the various sublayers of the molecular layer led to the conclusion that these cells migrate into denervated dendritic areas from neighboring, nondeafferented zones.     

Metabolism and distribution of bupivacaine-experiments in rats I. Methods and metabolism (author's transl)

A method is described enabling blood concentrations and urinary and biliary excretion of bupivacaine to be estimated in unanaesthetized rats. After enteral application of bupivacaine, the urine volumes of 40 rats are collected, cleared off and analysed by gas chromatography. 5 fractions are obtained, of which the structures are identified by mass spectrometry and nuclear magnetic resonance. The following five metabolites could be identified: (1) Desbutyl-bupivacaine, (2) 3'-Hydroxy-bupivacaine, (3) N-Butylpipecolyl-2-amide, (4, 5) mono-hydroxylated isomeres on the piperidine ring.     

Elongation of (omega-14C)oleic acid and (omega-14C)nervonic acid

During feeding experiments with [omega-14C]oleic acid and [omega-14c]nervonic acid to adult rats, 14C-labelled C26, C28 and C30 fatty acids were recovered from the intestinal mucosa, liver, plasma, kidney and stools. The structures of these fatty acids were determined by g.l.c., radio-g.l.c. and mass spectrometry. The Schmidt and Ginger degradation methods indicated that most of the 14C found in these extra-long fatty acids remained in the omega position. These radioactive extra-long fatty acids were found mainly in the polar lipids of rats killed 3 or 15 h after being fed on labelled oleic acid or nervonic acid. Rats killed 63 h later yielded only traces of these extra-long fatty acids. When the rats were given antibiotics or received the same radioactive fatty acids by intravenous injection, the labelled extra-long fatty acids could not be detected in any of the tissues. We conclude that they were probably synthesized by elongation of oleic acid and nervonic acid by intestinal micro-organisms (probably yeasts) and then absorbed by the intestinal mucosa.     

Identification of 4(-) states in the 14C(p,n)14N reaction at 135 MeV

The tadpole larva of solitary ascidians has 40 notochord cells in its tail. Of these cells, 32 in the anterior and middle part of the tail are derived from the A-line blastomeres, while 8 in the posterior part of the tail originate from the B-line blastomeres. Previous experiments involving continuous dissociation of daughter blastomeres from the first cleavage to the 110-cell stage suggested that cellular interactions may be involved in the formation of notochord cells. In the present study, the presumptive-notochord blastomeres isolated from the 32-cell embryos did not develop features of notochord. These results suggest that cellular interactions may be required for the fate specification of notochord, that is to say, notochord formation occurs as a result of inductive interaction between blastomeres. In order to confirm the involvement of induction in the determination of notochord and to identify the inducer blastomeres, the presumptive-notochord blastomeres at the 32-cell stage were coisolated or recombined with one of the surrounding blastomeres in a series of experiments. The results suggested that, for the A-line precursors, notochord differentiation occurs as the result of an inductive influence from vegetal blastomeres that include the presumptive-endoderm blastomeres and the presumptive-notochord blastomeres themselves. It was also suggested that induction of notochord is complete by the 64-cell stage and that inductive interactions have to be initiated before the decompaction of blastomeres during the 32-cell stage. Ascidians are Urochordata and are closely related to vertebrates. In vertebrates, it is well known that inductive interactions play a crucial role in the determination of notochord. It appears, therefore, that induction of notochord is common throughout the phylum Chordata.     

Absorption, distribution, and excretion of [14C]patulin by rats

Adult rats of both sexes were given a single oral dose of [14C] patulin and were sacrificed at various time intervals from 4 hr to 7 days following administration of the mycotoxin. Two groups of rats were employed; the treated group had been exposed to daily oral doses of unlabeled patulin (dissolved in pH 5.0 citrate buffer) in utero and for 41-66 wk after weaning, while the controls were given the buffer only throughout gestation and for 38-81 wk after weaning. Approximately 49% of the administered 14C radioactivity was recovered from feces and 36% from urine within 7 days after dosing. Most of the excretion of labeled material occurred within the first 24 hr. All of the 14C activity detected in the urine samples was either metabolites and/or conjugates of the original [14C]patulin. About 1-2% of the total radioactivity was recovered as 14CO2 from expired air. Carbon-14 radioactivity in various tissues and organs was determined throughout the 7 day period; the most significant retention site was the red blood cells.     

Metabolism of (14C) cefaclor, a cephalosporin antibiotic, in three species of laboratory animals

The metabolic fate of the orally effective cephalosporin antibiotic cefaclor (Lilly 99638) has been studied in rats, mice, and dogs. Cefaclor is efficiently absorbed from the gastrointestinal tract as the intact antibiotic. In rats and mice, cefaclor, for the most part, escapes metabolism in the body and is eliminated unchanged as unaltered antibiotic, primarily by renal excretion. In dogs, however, cefaclor is more labile to metabolism and only a portion of the administered antibiotic is eliminated unchanged via the kidney.     

Metabolism of 5'-ether prodrugs of 1-beta-D-arabinofuranosyl-E-5-(2-bromovinyl)uracil in rats

1-beta-D-Arabinofuranosyl-E-5-(2-bromovinyl)uracil (BV-araU) is a selective antiherpesviral agent that has been shown to be metabolically stable in mice. However, E-5-(2-bromovinyl)uracil (BVU) is the major metabolite found after oral dosing in animals other than mice. When BV-araU was given orally to germ-free rats, only small amounts of BVU were found in the plasma, suggesting an important role of enterobacteria in the formation of BVU. Then, the metabolism of BV-araU prodrugs was studied in specific-pathogen free rats to select oral prodrugs of BV-araU with enhanced metabolic stability. 5'-O-Ethyl BV-araU (Et-BV-araU) gave about a 2-fold higher BV-araU blood concentration 3 and 6 hr after administration than after oral dosing of BV-araU, while the level of BVU was lower. Other aliphatic alkyl prodrugs also gave a lower level of BVU, but did not give the same elevation in blood concentration of BV-araU as did Et-BV-araU. Dosing of 5'-O-acetyl BV-araU resulted in blood concentrations of BV-araU and BVU similar to those after oral administration of BV-araU. 5'-O-Aromatic alkyl prodrugs showed poor bioavailability. A nearly 2-fold higher urinary recovery rate was seen for Et-BV-araU than for BV-araU or 5'-O-acetyl BV-araU. The conversion of Et-BV-araU to BV-araU was demonstrated in vitro using rat liver extract in the presence of co-factors, although the reaction was slow. The 5'-O-aliphatic alkyl prodrugs were completely resistant to degradation by enterobacteria, whereas the esters were partially degraded to BVU. Et-BV-araU may be a useful oral prodrug of BV-araU due to its increased metabolic stability and bioavailability.     

Absorption, distribution and excretion of 14C-cefatrizine (14C-S-640 P) in rat (author''s transl)

The reliability and rapidity of methods utilizing radioimmunoassay ( RIA) for detecting chorionic gonadotropin (CG) and estrogens in plasma, competitive protein binding assay for plasma progestins, and the hemagglutination inhibition test for urinary CG in the diagnosis of early pregnancy was evaluated in baboons. The hemagglutination inhibition test for detection of urinary CG did not give satisfactory results as late as Day 25 of pregnancy. Confirmation of pregnancy could not be established on Days 8 and 12 of pregnancy by RIA of estrogens, progestins, or CG. However, detection of plasma CG by RIA was 96.6% successful by Day 16, though the method was time-consuming. However, the determination of plasma estrogens and progestins by RIA was determined more quickly on Day 16, and gave equally successful results as the RIA for CG.