URINARY CONVERSION PRODUCTS OF 16-EPIESTRIOL-16-C14 IN THE DOMESTIC FOWL.
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Two previously uncharacterized radioactive estrogen conjugates, 17beta-estradiol-17-beta-D-glucuronide (3-hydroxyestra-1,3,5(10)-trien-17beta-D-glucopyranosiduronate) and 17alpha-estradiol-17beta-D-glucuronide (3-hydroxyestra-1,3,5(10)-trien-17alpha-yl-beta-D-glucopyranosiduronate), have been identified in small but significant amounts in avian urine and in a ratio of approximately 2:1 after intramuscular injection of [4-14C]estrone.
Mucopolysaccharide-peptide complexes (MPS-P) from skin, comb, wattle, liver, kidney, spleen, lung, heart, ovaries, egg yolk, infundibulum, magnum, isthmus, shell gland, and vagina of the White Leghorn laying hens were isolated after extraction with acetone, papain hydrolysis, and cetyl pyridinium chloride precipitation. They were analyzed for characteristic components of the glycosaminoglycan (GAG) and carbohydrate parts of glycoproteins and for amino acids. The infrared spectra of the MPS-P were studied for detection of the GAG present. The MPS-P were submitted to cellulose acetate electrophoresis for detection of GAG and to column chromatography on an anionic resin for quantitative determination of GAG.
The incorporation of radioactivity from D-[1-14C]glucosamine and D-[1-14C]galactosamine into the tissues of skin, comb, wattle, liver, kidney, spleen, lung, heart, ovaries, egg yolk, infundibulum, magnum, isthmus, shell gland, and vagina of the White Leghorn laying hens was studied for different time intervals up to 120 h. A total of 28 laying hens were involved in this experimentation. The radioactivity was measured in the above whole tissue, the acetone extracts, the acetone-extracted tissues, the mucopolysaccharide-peptide complex (MPS-P), and in individual glycosaminoglycan (GAG) isolated from skin, comb, liver, kidney, and egg yolk. The radioactivities of the expired CO2 of the eggs and of the excreted urine and faeces were also measured in some cases. There was an increase in 14C associated with MPS-P with increasing time of experiment in all the tissues studied except in the case of the liver. The rate of increase of radioactivity was dependent on the tissue. A useful scheme for the study of the speed of the formation of GAG is to consider the acetone extract and the acetone-extracted tissue as macrocompartments from where the GAG draw hexosamines for their formation.
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The anticonvulsant activity of delta9-tetrahydrocannabinol (delta9-THC) has been determined against seizures induced in epileptic chickens by intermittent photic stimulation (IPS) and in epileptic and nonepileptic chickens by Metrazol. Intravenous administration of the drug reduced both the severity and incidence of seizures evoked by IPS in epileptic chickens. This anticonvulsant action was accompanied by a reduction in frequency of inter-ictal slow-wave high-voltage electroencephalographic activity and by the absence of spiking during IPS. delta9-THC did not affect the incidence of Metrazol-induced seizures in epileptic or nonepileptic chickens.
The relationship between plasma phenobarbital concentrations and anticonvulsant activity was determined against seizures induced in epileptic chickens by intermittent photic stimulation (IPS). Intraperitoneally administered phenobarbital produced a plasma-concentration-dependent reduction in both the incidence and severity of seizures. Complete protection against IPS-induced seizures was observed for a period of 6 h after acute phenobarbital administration during which the mean plasma phenobarbital concentrations were between 16.2 +/- 0.91 and 13.6 +/- 1.0 microgram/lm. Plasma phenobarbital concentrations below 3.6 +/- 0.06 microgram/ml had no measurable effect.
Acute dose-response studies with phenytoin were conducted to determine the relationship between plasma levels and anticonvulsant effect in epileptic chickens. Phenytoin produced statistically significant reductions in both the incidence and severity of seizures in photosensitive epileptic chickens when the plasma concentrations exceeded 8.15 +/- 0.89 microgram/ml. A high correlation exists between plasma phenytoin concentrations and both the reduction in incidence or severity of seizures. However, the appearance of plasma concentration dependent neurological toxicities resulted in a failure to achieve complete protection against intermittent photic stimulation induced seizures.
Primidone is an effective anticonvulsant against seizures induced in epileptic fowl by exposure to intermittent photic stimulation. Epileptic fowl metabolize primidone to phenobarbital. Pretreatment of epileptic fowl with SKF 525A to prevent the metabolism of primidone to phenobarbital indicated that primidone itself had anticonvulsant activity. Phenylethylmalonamide, a second metabolite of primidone, did not have anticonvulsant activity when administered at the same dose as primidone.