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Biomedical subjects

R Wade

Publications and source records attributed to R Wade.

84 records · Page 5Linked to original sources
PubMed1969

The isolation, identification and synthesis of two metabolites of guanethidine formed in pig and rabbit liver homogenates.

1. Two metabolites of radioactively labelled guanethidine were isolated from rabbit and pig liver homogenates by ion-exchange chromatography on a sulphonic acid resin. 2. One of the metabolites was eluted from the column with ammonia and identified as 2-(6-carboxyhexylamino)ethylguanidine on the basis of the elemental analysis, i.r. spectrum and pH titration curve of the pure compound, and the observed partial loss of tritium for ring-labelled guanethidine during the formation of this metabolite. 3. This identification was confirmed by synthesis. 4. 2-(6-Carboxyhexylamino)ethylguanidine underwent ring-closure in hot alkaline solution to 1-(6-carboxyhexyl)-2-iminoimidazolidine. 5. The other metabolite of guanethidine was eluted from the ion-exchange column with 6m-hydrochloric acid along with the unchanged drug. It was purified by countercurrent distribution and shown to be identical with synthetic guanethidine N-oxide. 6. The two metabolites and the product of ring-closure had less than one-tenth of the antihypertensive activity of guanethidine in the renal-hypertensive rat and are unlikely to contribute to the pharmacological properties of the drug.

Animals↗
PubMedDate not supplied

Pilot survey of urinary porphyrins from persons transiently exposed to a PCB transformer fire.

In rats and humans chronically exposed to large amounts of PCB (polychlorinated biphenyls) and PCDF (polychlorinated dibenzofurans), the urinary excretion of uroporphyrin and coproporphyrin are altered. However, porphyrin excretion in humans after acute transient low level exposure has not been evaluated. Following such an exposure in which bystanders and firefighters were in contact with smoke from a PCB transformer fire, we surveyed 90 self-referred individuals by questionnaire and by determining single 24 hour urinary excretion of uroporphyrin and coproporphyrin 2-4 weeks after the fire. Questionnaire variables that assessed exposure were not associated with the magnitude of either uroporphyrin or coproporphyrin excretion. Uroporphyrin excretion was slightly elevated in nine subjects (range 66-106 micrograms/24 hours, normal less than 60), which is much less than in clinical cases of porphyria cutanea tarda. Uroporphyrin excretion was inversely correlated with coproporphyrin excretion (r = -0.3844, p = 0.0002). For 5 subjects (3 with elevated initial uroporphyrin excretion) retested at 3-4 weeks after the fire, all 5 showed increases in uroporphyrin and decreases in coproporphyrin excretion when compared to initial determinations. These two reciprocal relationships would be the expected result from inhibition of uroporphyrinogen decarboxylase, a known experimental effect of PCB and PCDF in mice. Overall, urinary porphyrin excretions were not altered or sensitive measures of exposure.

Air Pollutants↗