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Biomedical subjects

W R Jondorf

Publications and source records attributed to W R Jondorf.

At least 19 recordsLinked to original sources
PubMed1989

Oxidative metabolism of 14C-pyridine by human and rat tissue subcellular fractions.

1. The oxidative metabolism of 14C-pyridine by human and rat microsomal fractions has been studied. Metabolites were separated by h.p.l.c. employing continuous radioactivity monitoring of the column effluent. 2. Human liver microsomal fractions incubated with an NADPH-generating system and oxygen formed pyridine N-oxide (PNO) at an average rate of 275 pmol/min per mg protein, 2-pyridone (2PO) at 207 pmol/min per mg and 4-pyridone (4PO) at 154 pmol/min per mg. One human subject formed 3-hydroxypyridine N-oxide in addition to the other metabolites. 3. Human kidney microsomal fractions formed PNO, 2PO and 4PO at rates similar to those with human liver microsomal fractions, whereas human lung microsomal fractions formed the metabolites at less than half the rate. 4. Metabolism of pyridine by human liver microsomal fractions was inhibited 54% by nitrogen, 34% by 80% carbon monoxide-20% oxygen, and 20% by metyrapone. 2-Diethylaminoethyl-2,2-diphenylvalerate HCl (SKF-525A) did not inhibit pyridine metabolism. 5. Liver microsomal fractions from non-induced rats metabolized pyridine to PNO at a rate of 19 pmol/min per mg protein, 2PO at 17 pmol/min per mg and 4PO at 61 pmol/min per mg. 6. There was no pyridine metabolism by human or rat tissue cytosolic fractions incubated under the same conditions.

Animals↗
PubMed1989

19-nortestosterone detection in canine plasma after intramuscular administration of 19-nortestosterone phenylpropionate.

A proven radioimmunoassay method for monitoring 19-nortestosterone (nandrolone) was combined with high pressure chromatographic fractionation on a microparticulate silica gel using 1,2 dichloroethane/ethanol as the mobile phase. Plasma levels of 19-nortestosterone were monitored for seven days after intramuscular administration of nandrolone phenylpropionate (1.5 mg kg-1) to a beagle and a German shepherd dog. After 24 hours the plasma level in both bitches was 20 ng ml-1 and reverted to baseline after the fourth day after injection. Nandrolone was shown to be the only detectable exogenous steroid present in the post injection plasmas and could be distinguished from any potential cross reacting metabolites. The radioimmunoassay method can therefore be applied to the evaluation of nandrolone in the management of canine chronic renal disease in the bitch.

Anabolic Agents↗
PubMed1988

Differences in adipose tissue distribution of basic lipophilic drugs between intraperitoneal and other routes of administration.

1. Distribution of 14C-methadone in male rats was studied after administration of single i.p. doses. Highest concentrations were attained after 30 min in the decreasing order of abdominal adipose tissues, liver, lung, other organs. Concentrations in abdominal adipose tissues were 20 times higher than in subcutaneous adipose tissue. This is in contrast with what occurs with other routes of administrations, where only low concentrations are attained in both subcutaneous and abdominal adipose tissues. 2. The situation in the peritoneal cavity after i.p. injection was simulated in vitro by incubation of whole, excised abdominal adipose tissues of rats with methadone and other basic drugs (dibenzepine, alprenolol, opipramol, propranolol, chlorpheniramine, desipramine, imipramine and chlorpromazine) for 6 h at pH 7.4. These drugs were readily taken up (25 to 74% at equilibrium). 3. There was a positive correlation between uptake and lipophilicity of the drugs as measured by log P (octanol/water). Less lipophilic drugs such as amphetamine, morphine and chlorphentermine were not appreciably taken up from the incubation medium. The threshold log P-value for appreciable adipose tissue uptake is around 2. 4. It is concluded from these data and related studies that basic lipophilic drugs are not stored in adipose tissues in vivo, except when given via the i.p. route. In the latter case the storage appears to result from non-systemic, diffusional uptake from the peritoneal cavity.

Adipose Tissue↗
PubMed1978

Radioimmunoassay technique for detecting urinary excretion products after administration of synthetic anabolic steroids to the horse.

1. Cross-bred and thoroughbred geldings were injected with veterinary doses of various synthetic anabolic steroids. Urines collected sequentially from treated animals were analysed, following solvent extraction, by radioimmunoassay using 19-[3H]nortestosterone and an antibody raised against a 19-nortestosterone immunogen. 2. Urinary excretion of 19-nortestosterone and/or its cross-reacting metabolites was detectable for various times after administration of different nortestosterone esters, as follows: phenylpropionate (400 mg), greater than 14 days; cyclohexylpropionate (100 mg), greather than 10 days; laurate (200 mg) greater than 50 days. After administration of the parent steroid (150 mg) cross-reacting compounds were detectable in urine for ca. 3 days. 3. Urinary excretion of esters of other anabolic steroids cross-reacting with the 19-nortestosterone antibody (e.g. 1-dehydrotestosterone and trienbolone) could also be followed by analysing solvent extracts of urines by the radioimmunoassay. Cross-reacting compounds in urine after administration of 1-dehydrotestosterone undecylenate (250 mg) and trienbolone acetate (75 mg) could be detected for greater than 35 days and greather than 5 days, respectively.

Anabolic Agents↗
PubMed1977

19-nortestosterone, a model for the use of anabolic steroid conjugates in raising antibodies for radioimmunoassay.

1. The raising of antibodies in Soay sheep to an immunogenic conjugate of 19-nortestosterone-3-(O-carboxymethyl)oxime with bovine serum albumin is described. 2. High titre plasma so obtained can be used for the radioimmunoassay of 19-nortestosterone. 3. Cross-reactivities of the antibody with endogenous steroids is confined to testosterone (20-25%) and 17beta-estradiol (1-2%). Cross-reactivities with a range of other 17beta-hydroxy synthetic anabolic steroids and with some potential 17beta-hydroxy metabolites of 19-nortestosterone vary between 2-3% for 5beta-estrane-3alpha,17beta-diol and 26% for 1-dehydrotestosterone. There is limited cross-reactivity (ca. 1-2%) with anabolic steroids with 17beta-hydroxy, 17alpha-methyl substituents. 4. 19-Nortestosterone (phenyl propionate) administered to a horse (1 mg/kg, intra-muscular) gives urinary metabolites readily detectable by radioimmunoassay, for more than 4 days.

Animals↗
PubMed1976

Phosphonomethyl analogues of hexose phosphates.

The analogue of fructose 1,6-bisphosphate in which the phosphate group, -O-PO3H2, on C-6 is replaced by the phosphonomethyl group, -CH2-PO3H2, was made enzymically from the corresponding analogue of 3-phosphoglycerate. It was a substrate for aldolase, which was used to form it, but not for fructose 1,6-bisphosphatase. It was hydrolysed chemically to yield the corresponding analogue of fructose 6-phosphate [i.e. 6-deoxy-6-(phosphonomethyl)-D-fructose, or, more strictly, 6,7-dideoxy-7-phosphono-D-arabino-2-heptulose]. This proved to be a substrate for the sequential actions of glucose 6-phosphate isomerase, glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase. Thus seven out of the nine enzymes of the glycolytic and pentose phosphate pathways so far tested catalyse the reactions of the phosphonomethyl isosteres of their substrates.

Fructose-Bisphosphatase↗
PubMed1976

Development of liver microsomal oxidations in the chick.

1. Liver microsomal preparations from chick embryos (1 day before hatching) and from 1-7 day old chicks were assayed for oxidative drug-metabolizing activity with aminopyrine, aniline and naphthalene as substrates. 2. Activities for all three substrates were highest in preparations from 1 day-old chicks. These were more than twice as active as the 7 day-old preparations and about three times as active as those from the embryos. 3. The increase in drug-metabolizing activities in newly-hatched chicks was the same for either sex and persisted for 3 days before declining towards the 7 day-old levels. 4. The developmental time-course fo the liver microsomal drug-metabolizing activities was independent of any factor in the 105 000 g supernatant fractions and of such microsomal parameters as cytochrome b5 and cytochrome P-450 content, and NADPH-cytochrome c reductase activity, but was related to changes in NADPH-cytochrome P-450 reductase levels. 5. Treatment of 7 day-old chicks with exogenous inducers, 3-methylcholanthrene or phenobarbital sodium (100 mg/kg, intraperitoneally) brought about maximal stimulation of microsomal activity as 18-24 h. The time-course of this induction was reflected by changes in microsomal cytochrome P-450 content and NADPH-cytochrome P=450 reductase activities. 6. Some induction of liver microsomal drug metabolism in 7 day-old chicks could also be brought about by injecting certain lipid-soluble egg yolk extracts.

Aging↗
PubMed1974

Some inhibitory effects of (--)-emetine on growth of Ehrlich ascites carcinoma.

(-)-Emetine has little or no effect on O(2) consumption of Ehrlich ascites-cell suspensions or on the viability of transplanted Ehrlich ascites-tumour cells exposed to, or incubated with, the drug in vitro before inoculation into new-host mice. (-)-Emetine administered as a single injection to mice bearing Ehrlich ascites-tumour cells slows the growth rate of the tumour. The subcutaneous or intraperitoneal injection of the drug depresses protein and DNA synthesis of the tumour cells in vivo in a reversible manner. Mice bearing ascitic sarcoma 180 or Ehrlich ascites-tumour cells when given a course of treatment with (-)-emetine or (-)-O-methyltubulosine have a substantially lower tumour load than untreated controls and correspondingly longer survival times.

Animals↗